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results, revised and approved the final version of the manuscript.The authors apologize for any inconvenience caused."} +{"text": "Given the limited evidence of school closure effectiveness in containing the pandemic and the consequences for young people, reopening schools with appropriate measures is essential. This overview aimed to describe the main measures planned for the 2020\u20132021 academic year within the WHO European Region. A rapid systematic review of scientific databases was also performed. The websites of the government, Ministry of Health, and Ministry of Education of European Region countries were searched through 1 October for official documents about the prevention and management of suspected cases/confirmed cases in primary and secondary schools. To find further suggestions, a rapid systematic review was conducted through 20 October searching Pubmed, Scopus, and Embase. There were 23 official documents. France, Luxembourg, Malta, Ireland, Italy, Portugal, the UK, Spain, and San Marino were considered. Performing the rapid review, 855 records were identified and 7 papers were finally selected. The recommendations mostly agreed. However, there was no consensus on the criteria for the return to school of students that tested positive, and the flexibility between attendance at school and remote education for high-risk children often varied. School closure was commonly considered as the very last resort for COVID-19 control. Studies are required to evaluate the impact of different recommendations during this autumn term. Up to early October 2020, coronavirus disease 19 (COVID-19) presented a cumulative total of over 34 million cases and over 1 million deaths worldwide. The majority of deaths have been reported in the World Health Organization (WHO) Region of the Americas (55%) and the WHO Region of Europe (23%). In numerous countries, especially in the European Region, the second wave has been greater than the past peaks, partially due to an improvement in surveillance efficiency. Focusing on the European Region, the incidence of new cases is constantly increasing, with France, the Russian Federation, the United Kingdom (UK), Spain, and Israel reporting the greatest number of new cases in the first week of October [In this context, less than 5% of cases in the European Economic Area and the UK have been reported to occur in young people aged 18 years and under . SpecifiAlthough outbreaks in schools have been reported, their detection is extremely difficult because of the poor presentation of symptoms among younger people , and theNotably, strategies less disruptive than school closure must be considered in a context where restrictive distancing policies are enacted for long periods, as school closures can lead to very high costs both in economic and social fields . In partTherefore, given the limited evidence of school closure effectiveness in containing the pandemic and the importance of the consequences of school closure on young people\u2019s lives, it seems essential to implement preventive measures when reopening schools, along with clear strategies to manage potential cases and outbreaks in school settings, in order to reduce the transmission of COVID-19 and keep schools open.In September, with the beginning of the academic year 2020/2021, the vast majority of the countries belonging to the WHO European Region fully reopened schools . Thus, tThe present investigation was directed to all countries included in the European Region of WHO in orderThe search strategy research was structured using the PICOS strategy, as can be seen in Documents were considered eligible if they reported official detailed guidelines or protocols on the reopening measures to be followed in school settings both to prevent the COVID-19 transmission and to manage suspected/confirmed cases of COVID-19 infection. The authors examined only documents written in English, French, Spanish, Italian, or Portuguese. Only state-level documents and documents referring to the academic year 2020/2021 (or autumn term) were included. Only documents on primary and secondary schools were considered eligible, while information about preschools, colleges, and universities were excluded. News, statements, and question and answer pages were excluded. Two authors (GLM and TS) independently screened the websites of the government, Ministry of Health, and Ministry of Education to identify relevant documents. Disagreements were resolved by consensus. Extracted data for preventives measures included publication date, information about attendance, masks, physical distancing, interactions and behaviors, hand hygiene, ventilation, cleaning and disinfection, physical activity, school transport, and canteens. Extracted data for management measures included publication date, information about the management of students (and staff) with symptoms, and information about the management of students (and staff) who test positive.In order to find further suggestions for preventive and management measures, a rapid systematic review ,17 was cStudies were considered eligible if they reported guidelines, recommendations, or protocols for the reopening of primary and secondary schools. Differently from the search for official documents described above, papers referring to the reopening of schools before the new academic year 2020/2021 were included. Only papers that reported measures concerning the prevention of COVID-19 transmission or the management of suspected/confirmed cases were considered eligible. The authors examined only studies written in English, French, Spanish, Italian, or Portuguese. Commentaries and letters were excluded. Other exclusion criteria were studies on preschools, colleges, and universities and the unavailability of full texts. Authors chose the web application Rayyan of the Qatar Computing Research Institute (QCRI) as a tool for selecting and extracting relevant studies . Three aOverall, due to language restrictions, the countries included in this overview were the following: France, Ireland, Italy, Luxembourg, Malta, Portugal, Spain, the United Kingdom, and San Marino. n = 2) [n = 2) [n = 1) [n = 4) [n = 5) [n = 3) [n = 2) [n = 3) [n = 1) [The number of official documents identified and considered relevant in the present overview was 23. The documents belonged to the following countries: France (n = 2) ,23, Luxe [n = 2) ,25, Malt [n = 1) , Ireland [n = 4) ,28,29,30 [n = 5) ,33,34,35 [n = 3) ,37,38, t [n = 2) ,40, Spai [n = 3) ,42,43, a [n = 1) . These d [n = 1) and Octo [n = 1) ,34,42,44 [n = 1) ,25 were [n = 1) were ava [n = 1) ,39,40, t [n = 1) ,30,34,42 [n = 1) ,43,44. T [n = 1) ,37,39,42 [n = 1) ,44, and Performing the rapid systematic review, a total of 855 records were identified. The study selection process is described in Attendance and remote education: All students are expected to return to school [o school ,39,41,42o school ,35,36,37o school ,26. Someo school ,32,41,42o school ,39. In so school ,24,26,39Masks:Physical distancing: Physical distancing is considered one of the most important preventive measures in all documents. Distances range from a minimum of 1 m to a minimum of 2 m, and usually the distance that should be kept is higher between members of staff and students than between students and touching face and mask [and mask ,37,41,42and mask ,37, encoand mask ,28,29, aand mask ,28.Hand hygiene: Promotion and reinforcement of hand hygiene practice is strongly encouraged, and it is preferable to use warm water and soap in all countries. It is possible to use hand sanitizer but when hands are visibly dirt use water and soap [and soap ,28,41,42and soap . Hand hyand soap ,39,41,42and soap ,27,28,32and soap ,26,39.Ventilation, cleaning and disinfection: All the countries highlighted the importance of an adequate ventilation of all areas. For instance, ventilation should be ensured before entrance, during break, end of the day [ the day ,41,42, a the day , during the day . Ventila the day ,41,42 an the day ,26,41,42 the day ,26,27,28 the day ,39,41,42 the day ,39, at l the day ,32 or thPhysical activity at school: Outdoor activities should be preferred [referred ,38,39,42referred ,39, e.g.referred ,28,31,32referred ,37. In areferred ,39, indireferred ,38. Lastreferred ,38.School transports: Masks are mandatory [andatory ,41,42,44andatory or 6 yeaandatory ,33,41,42andatory and in Iandatory . Staggerandatory ,28,39, dandatory ,33,36,39andatory ,33,36,39andatory ,33,36. Tandatory ,39. Lastandatory ,28,41.School canteens: School canteens are reopening in all countries. Among the main measures to be followed, it is clarified to wear a mask until sitting [ sitting ,36, keep sitting ,32,41,42 sitting , stagger sitting ,32,36,37 sitting ,36,41,42 sitting ,28,41,42Attendance and remote education: Remote education should be feasible in all educational facilities, as this might prevent potential exposure or transmission among staff and children. In the case of a high incidence of COVID-19 transmission divided classes, supplemented by online lessons should be implemented [lemented . Alternalemented . The guilemented . Insteadlemented , whereaslemented .Masks: Recommendations for the use of masks differ among documents , self-isolate and call healthcare providers to receive instructions and get tested if COVID-19 is suspected. The procedure to follow is comparable to the procedure recommended for students. In some cases, it is specified that school workers have priority access to testing ,39.Confirmed case: In case the student is confirmed to be positive, the return-to-school criteria defined by the countries were mostly different, as reported in All the countries consider the quarantine of close contacts in school (staff and students), except Luxembourg, and report that the school should provide a list of contacts to health authorities, which perform risk assessment, epidemiological investigation, contact tracing, and guide the actions to be followed. When specified, the duration of quarantine can range from 7 days to 10 4 and 14 dSome documents clarify also the measures that must be taken if more than one case in one classroom is confirmed. In Luxembourg, if the transmission is identified outside school the base scenario remains the same and the involved classroom is quarantined and tested; if the transmission is within school, more restrictive measures should be implemented by a specific committee . In someSuspected case: These documents commonly disagree on measures to be implemented if suspected and confirmed cases occur within schools. For instance, only the German consensus statement requires the presence of a COVID-19 contact person at school [t school . A desigt school , whereast school . The latt school . Moreovet school . None oft school ,48. Thist school . Insteadt school , while masks were usually not recommended for primary school students (or a risk-based approach was advised). One of the main differences we found was regarding students at high risk due to their medical conditions. Indeed, in some cases there was flexibility between attendance in presence or remote education, while in other cases all students were expected to physically return to school without exceptions. We argue that a one size fits all approach for high-risk children should not be the chosen approach ,52. SeveRegarding the management of suspected and confirmed cases, the official documents mostly agreed. The existence of a specific COVID-19 contact person in the school and the location of the first call to have a telephone triage were among the main differences in the first step to be followed. In addition, the criteria to return to school for suspected and confirmed cases were slightly different among countries . HoweverOverall, the official documentation taken into account in the present overview included the recommendations outlined in the WHO, United Nations Educational, Scientific and Cultural Organization (UNESCO), and United Nations International Children\u2019s Emergency Fund (UNICEF) document published in September . Indeed,The present work has some limitations that must be acknowledged. Above all, language represented one of the main limitations, as well as the limited sources of information used. Indeed, besides the government, Ministry of Health, and Ministry of Education websites that were searched, additional official documentation might be found in other official websites. In addition, we decided to consider only state-level guidelines, therefore further details and differences that can potentially be highlighted in regional or local guidelines are missing. Similarly, the rapid review of scientific literature cannot provide an immediate and prompt update of recommendations, as scientific publications require a certain amount of time to be peer-reviewed. Moreover, conducting a rapid systematic review may be itself a limitation, with the search being less extensive and comprehensive than a systematic review. Nevertheless, the present paper had the primary aim of providing an overview of the possible guidelines to be implemented for the 2020/2021 academic year reopening and, through a detailed comparison, allowed us to highlight both the commonly shared recommendations and the mainly different recommendations. It also outlined the broad heterogeneity of details that state-level guidelines provide.In conclusion, the present paper showed that the recommendations and guidelines for reopening primary and secondary schools in the 2020/2021 academic year were mostly in agreement considering the measures of prevention and management of suspected and confirmed cases. However, among the differences that were found, this overview also showed that there was no strict consensus on the criteria for the return to school of students that tested positive and, therefore, we suggest that evidence on which criteria are more effective in limiting the transmission should be gathered. Additionally, it is worth noting that the flexibility between attendance at school and remote education for high-risk children varied across countries and papers. In our opinion, special attention should be paid to high-risk children; in particular, a one size fits all approach should not be the chosen approach. Lastly, the fact that school closure was commonly considered as the very last resort for COVID-19 control is extremely important in view of the widespread consequences that have been reported due to school closures in the past months ,11,12,13Further studies are required to evaluate the impact of the different recommendations on controlling COVID-19 transmission in schools during this autumn term, and expert meetings may be useful in order to discuss available evidence. Moreover, we argue that the human factor should be also evaluated along with the effectiveness of the strategies per se. Indeed, suboptimal compliance to hygiene practice has been reported both at the school level and the"} +{"text": "ESC Heart Failure (ESC\u2010HF) is an open access journal focused on advancing the understanding of heart failure since 2014. It is one of two journals of the Heart Failure Association of the European Society of Cardiology . ESC\u2010HF is published by Wiley as its publishing house. The journal's main topics include basic and translational research questions regarding the pathophysiology, electrophysiology, and biology of heart failure; clinical questions regarding the prevention, diagnosis, understanding, and therapy of heart failure; and epidemiological questions regarding the incidence, prevalence, prevention, distribution, and risk factors for heart failure in different populations. The workload regarding submitted journals is distributed between Prof. Stefan D. Anker , the editor\u2010in\u2010chief, and the three deputy editors Prof. Stephan von Haehling for the clinical section, Prof. Zolt\u00e1n Papp for the basic science section, and Dr G\u00e1bor F\u00f6ldes for translational research. However, the journal would not be feasible without the help of the many authors and reviewers, editorial board members, associate editors, and especially the editorial office with Monika Diek, Anja Janssen, and Corinna Denecke. This journal relies on all these people to work together, towards the same goal of better understanding heart failure and its treatment.While in 2014, new journal issues were published every 6\u00a0months, today every 2\u00a0months a new issue is published. Thereby, the number of articles steadily increased over the years\u20142014, 16; 2015 and 2016, both 41; 2017, 95; 2018, 131; and 2019, 149. This is a ninefold increase of published articles from 2014 until 2019. At the time of this writing in September 2020, the number of submissions in 2020 has reached 926. The journal attracts publications from many different nations. The list of countries where most of the articles originate includes Germany, the United States, Japan, England, Italy, Netherland, Spain, Sweden, France, and Australia.TableTablesIn Web of Science,In 2019, ESC\u2010HF articles were altogether cited 1276 times.None declared."} +{"text": "Some epidermal alterations in measles has been described, such as keratinocytes apoptotic, parakeratosis, giant-cell formation, intranuclear and cytoplasmic inclusions, dyskeratosis, spongiosis, and intracellular edema. The authors report for the first time in human a case of measles with the presence of multinucleated giant cells in the hair follicle and dyskeratosis in acrosyringium. A 9-year-old boy evolved with headache and fever. Seven days after the onset of symptoms, coughing, an episode of hemoptysis, coryza, and conjunctivitis, followed by a rash that started on the forehead with a cephalophaudal progression. He had no comorbidities or family history.The exanthema was distributed in a cephalocaudal direction, with appearance of pruritic maculopapular lesions, some confluent plaques, more intense on the face and trunk. The physical examination revealed a hypochromic macula, with diffuse erythematosus halo, before the appearance of a rash on the oral mucosa, Koplik's sign , besidesThe skin biopsy showed hyperkeratosis, mild spongiosis, dyskeratosis, focal parakeratosis, and apoptotic keratinocytes. In follicular epithelia, was observed dyskeratosis and multinucleated giant cells . The dysTorres, in 1952,The most common findings are parakeratosis, giant-cell formation, intranuclear and cytoplasmic inclusions, dyskeratosis, spongiosis, and intracellular edema.EwingEpithelial giant cells in the hair follicles were described, in our knowledge, only by Hall et al.None declared.Monique Freire Santana: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; critical review of the literature; critical review of the manuscript.Luiz Carlos de Lima Ferreira: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; critical review of the manuscript.Jo\u00e3o Gabriel Nogueira de Oliveira: Elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data.F\u00e1bio Francesconi: Effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.None declared."} +{"text": "Sphenarium that are widely looked for, collected, accepted as part of the diet, consumed, and marketed.In the state of Michoac\u00e1n, Mexico, 49 genera and 69 species of edible insects were registered, and they belong to the following orders: Orthoptera: (families) Pyrgomorphidae (2 species) and Acrididae (5); Hemiptera-Heteroptera: Coreidae (1), Corixidae (2), Pentatomidae (2), Membracidae (2), and Aethalionidae (3); Coleoptera: Cerambycidae (1), Cicendelidae (2), Curculionidae (2), Dytiscidae (1), Noteridae (1), Gyrinidae (1), Passalidae (1), Scarabaeidae (1), Tenebrionidae (2), Bostrichidae (1), Buprestidae (1), and Melolonthidae (1); Lepidoptera: Cossidae (1), Danaidae (1), Megathymidae (1), Pieridae (1), Bombycidae (1), Sessidae (1), Noctuidae (1), and Nymphalidae (1); Diptera: Stratiomydae (2); and Hymenoptera: Diprionidae (2), Apidae (10), Formicidae (4), and Vespidae (12). The order Coleoptera presents the highest number of families (12), but the order Hymenoptera has the highest number of genera (18) and species (28), 12 of which belong to the family Vespidae. Among the genera, 75.52% are monospecific, 14.28% are bispecific, 4.08% are trispecific, 4.08% are tetraspecific, and 2.04% are pentaspecific. Their distribution by locality is indicated, and these localities correspond to the municipalities of the state sampled so far; likewise, we report various forms in which they are prepared and the economic importance of, for example, the grasshoppers of the genus Society currently faces a variety of significant crises. Preexisting quotidian crises are now accompanied by drastic climate fluctuations caused by global warming, including issues such as rising pollution, unchecked demographic growth, and low crop yield. As a result, to feed an ever-growing world population, insects are an important alimentary resource. Not only do many animals feed on them, but they also have a long culinary history providing food for people in different parts of the world: these animals have been valued by many cultures and for some are the sole protein source available . Being a2. The topography of the state include Sierra Tarasca in the north pertaining to the Eje Volc\u00e1nico along with numerous volcanoes, such as Zacap\u00fa; the main mountain ranges such as the ones of Angangueo in the limits of the Estado de M\u00e9xico; Ucareo, Mil Cumbres, and Otzumatl\u00e1n; the Pico de Orizaba; mount Zirate; the Sierra de Patamb\u00e1n; mount Tanc\u00edtaro; Sierra de Inguar\u00e1n; the Paricut\u00edn and Jorullo volcanoes; and the northern part of the R\u00edo Tepalcatepec basin contained the flatlands of Antunez, Lombardia, and Nueva Italia. Sierras Tarasca and Coalcam\u00e1n have a subhumid temperate climate, and the mountainsides toward the basins of Tepalcatepec and Balsas and toward the Pac\u00edfic are hot humid and the lower part of that basin is semi-dry with a summer rainfall regime. The following rivers are present in the state: Coahuayana, Coire, Coalcam\u00e1n, Nexpa, Carrizal, and Zacatula; the last one has numerous tributaries in the state, such as the Grande, which also receives water from the Cupatitzio or del Marqu\u00e9s and forms the waterfall known as the Tzar\u00e1racua at the south of the city of Uruap\u00e1n, the Tac\u00e1mbaro, the Car\u00e1cuaro, the Cutzamala, the Tuzantla, the Tuxpan, the Zit\u00e1cuaro, and the Temascaltepec. The river Lerma marks boundaries between Michoac\u00e1n and the states of Quer\u00e9taro, Guanajuato, and Jalisco; the closed basins include lakes Cuitzeo, P\u00e1tzcuaro, and Zirahu\u00e9n. The state also has numerous springs of thermal and mineral-medicinal waters. In the Sierra Madre del Sur, the soils are poor and undeveloped, such as the regosols and cambisols; in the Sierra Tarasca, the soils are fertile and derive from volcanic ash (andosols); and in the Balsas basin, the soils are clayey lateritic (acrisol and luvisol) alternating with cambisol. The state is divided into 113 municipalities and 7,716 localities. Of the total area of the state, 33.3% is farmland, 30.4% is rainfed, and 4.9% is irrigated, that is, Michoac\u00e1n is an agricultural state that produces corn, sorghum, rice, beans, wheat, barley, safflower, sesame, sugar cane, cotton, alfalfa, potatoes, and tomatoes and fruits such as strawberries, melons, avocados, lemons, mangos, apples, watermelons, and bananas. Grasslands compromise 6.7% of the total state area. Bovine cattle are the most important type of livestock, significant of which were the porcine, along with goats, sheep, horses, mules, and donkeys being bred. The total forest area is of 4,320,800; 2,052,800 ha are covered in trees, and of these, 1,733,200 ha has temperate and semicold climate forests and 319,000 medium forests, low forests, and mezquital correspond to 867,600 ha, shrubland to 259,200 ha and the areas that have been cleared so as to be used otherwise represent 1,141,200 ha. Pines, oaks, and firs are exploited for their wood; resin is obtained from pines. Fishing activities in its lakes are also important for its economy; the main species are charal, carp, catfish, frog, white fish, huachinango, tilapia, and sardine and/or municipal markets.During 2017 and 2019, diverse visits to 48 localities were carried out so as to survey and collect the edible insects. With this in mind, we developed a questionnaire exclusively aimed at the inhabitants of rural areas in which we asked about the insects included in their diet, their common names and hosts, and their gastronomic importance. Edible insects were collected using tweezers and entomological nets ; they were then placed in plastic jars filled with 70% ethanol for their preservation. In all the samples collected, we included the following data: locality name, collection date, collector's name, common name, and type of host . SeveralAfter their collection, insects were brought to the Entomology Laboratory that is part of the Department of Zoology of the Biology Institute, where they were mounted, labeled , and ideIn alphabetical order, the localities sampled were: Ahuiran, Alto Balsas, Angangueo, Aquila, Aranza, Ario de Rosales, Capacuaro, Angahuan, Chauzingo, Charapan, Cher\u00e1n, Cocucho, Cop\u00e1ndaro de Galeana, Cotija, Eronganicuaro, Jerecuaro, Jiquilpan, Juchit\u00e1n, Jungapeo, La Piedad, Lago de Cuitzeo, Lago de P\u00e1tzcuaro, Las Cocinas, Mazamitla, Meseta Tarasca, Morelia, Nahuatzen, Neocup\u00e9taro, P\u00e1tzcuaro, Pomocuaran, Quinceo, San Francisco Corupo, San Lorenzo, San Pedro Tarimbaro, Sevina, Tac\u00e1mbaro, Tecom\u00e1n, Tingambato, Tlalpujahua, Tumbizca, Tupataro, Tuxpan, Uruapan, Zac\u00e1n, Zamora, Zirahuen, Zit\u00e1cuaro, and Ziracuaretiro. The collection sites include pine-oak forests, ravines, shrubland, hills, and springs.Table 2.The edible insects reported by the persons interviewed are presented in In this study, we report 6 orders, 31 families, 49 genera, and 69 species.Trichoderes pini are both larvae and pupae are eaten, and, in the genus Cysbister, the larvae and adults are eaten. It is convenient to point out that the larvae are the most digestible in the developmental stage as they possess the smallest quantity of \u201craw fiber\u201d and that the adults are consumed in very few cases.The order Coleoptera has the highest number of families Ceramby. In thisPolybia, the consumption of honey is well-known and reproducing adults are consumed in the case of the ants of the genus Atta. A taxonomic synthesis is presented in The order Hymenoptera has the highest number of genera and specWe also record common or linguistic names, where the edible stage of development and the localities in which the consumption was recorded .Corisella mercenaria, Krizousacorixa femorata, Cybister sp., Suphisellus sp., and Gyrinus parcus), and 92.76% are terrestrial.Five species have an aquatic habit, that is, 7.24% , before being prepared in diverse dishes, are dehydrated in a microwave oven to eliminate excess water and, if they are used in the preparation of a sweet dish, they are placed in a container with sugar and cinnamon, boiled, and then microwaved. With grasshoppers, they make stuffed sweet crepes with a chocolate covering, cheese pie with kiwi and strawberries, rice and milk, pizza, and tacos with tomato sauce. These grasshoppers are also consumed as an appetizer; they are toasted and seasoned with piquing chili or they are cooked so as to be eaten in tacos accompanied by guacamole or sauce. They are also prepared in a sauce made of morita chili, garlic, and tomatillo and are sold in the streets, fried and seasoned with lemon and chili. They are used in the design of delicious gourmet dishes.Detailed below are some forms of preparation used in Michoac\u00e1n of some of the edible insects recorded. Order Orthoptera encompasses many phytophagous species that are pests, of which some are also predators; in this order, the nymphs and adults of grasshoppers are the Mexican edible insects most sought after, asked for, and commercialized in several states like Tlaxcala and Puebla, and they even have given rise to alimentary industries in Oaxaca. The grasshoppers are bug species pertaining to the family Pentatomidae that are considered to be a delicacy, where both nymphs and adults are consumed. The best known in the state is Brochyymena tenebrosa; these organisms can be eaten fried or ground to prepare a sauce and they may also be prepared in enchiladas is considered a delicacy since pre-Hispanic times and it is consumed toasted. The cocopaches (nymphs and adults) are eaten prepared in a sauce of chopped greens known as \u201cpico de gallo\u201d (rooster's beak).For order Hemiptera, we see the following: The chiladas . The axamayates, beetles, ladybirds, weevils, and picudos. They feed on both live and dead organic matter and, thus, they are important agricultural and forest pests; nevertheless, some of them are used in pest control. In Mexico, members of 22 families, 66 genera, and 119 species are consumed , they are cooked and filled with cheddar or mozzarella cheese, wrapped in a piece of bacon and accompanied by a cherry tomato, presented as sweet brochettes with kiwi, strawberry, and pineapple; as chocolate covered larvae; or as salted brochettes with broccoli, carrots, onions, and green pepper with a yellow dip with garlic; and as Chinese rolls with cream cheese and cucumber in a soy sauce. Depending on which flavor is selected when they are prepared, if it is salty they are fried in olive oil with salt and garlic, and if it is sweet with butter and sugar; and it is important to emphasize that the smell perceived during this preparation process is delightful, and it invites its savoring.In the case of grub worms (cupiches (larvae), huenches, conduchas, or chamas (pupae) are toasted in a comal and are eaten in tacos accompanied by hot sauce. Red and white maguey worms (larvae) are eaten in tacos.For the order Lepidoptera, we see the following: It encompasses the insects known as butterflies and moths, and among them, the edible ones that are most popular are the white and red maguey worms that are distributed in all states of Mexico where this plant grows. The Apis mellifera, while others are involved in pollination and biological control.For order Hymenoptera, we see the following: This order is equally one of the most numerous species, which are known by the common names of wasps, bees, and ants, that are beneficial, and some have been domesticated, as is the case of the bee Apis) are prepared with chantilly cream cheese filled strawberries, the strawberries are cored and filled with the mix of the cheese, cream, and larvae; they can also be added to rum-flamed bananas or to the custard used for filling pies; larvae are added directly to the dishes, giving them a sweet and pine nut like flavor. The reproductive adults of the chicatana ants are consumed fried and roasted and in sauces; another preparation form is to toast them and then grind them in a molcajete with chili, garlic, and salt so as to be eaten in tacos.Bee larvae , grasshopper flour, grasshopper and chinicuil chocolates, and caramelized grasshoppers. She says that the acceptance of these foodstuffs has been growing in Morelia, the capital city of the state, especially in the health sector due to the nutritional virtues of insects that, as we have already mentioned, are widely documented in the scientific literature, both in Mexico and worldwide. This firm also organizes training courses in rural zones where they show how to collect, clean, and prepare them for their sale, so as to ensure that they are innocuous in the processed products. This activity has become the source of income of many persons who are now devoted to collecting grasshoppers for human consumption. This is proof that this activity enables them to obtain a significant income , whose founder, the entrepreneur Janette Lagunas Rayas, has published that the market of insect consumption is growing slowly, but it is nevertheless growing . This cot income , 65, forth flour . Some fath flour . In thisOther insects that have economic importance in diverse ways include the bees known as Uauapu bees . Honey is sold in local and regional markets. Honey is considered a very rich foodstuff both for its flavor as well as for its nutritional properties; it is consumed because people like it and it is considered a privileged foodstuff. The honeycomb is also sold commercially and eaten in sliced pieces, and the larvae are consumed as well . Honey iIn the state of Michoac\u00e1n, Mexico, 69 species of edible insects in their different stages of development are consumed. The localities in which the greatest number of species are consumed are: Charapan (10 species) Jungapeo (7), P\u00e1tzcuaro (6), San Pedro Tar\u00edmbaro (6), Neocup\u00e9taro (6), and Cher\u00e1n (6).Anthropo-entomaphagy persists in Michoac\u00e1n due to its rural population that, despite the influence of miscegenation and the introduction of other alimentary habits, has kept its traditional knowledge about the ecology, distribution, management, and consumption of edible insects as these arthropods have been part of culture since pre-Hispanic times. They have been a significant aspect of Mexican cuisine and diet for centuries. Today, many chefs have incorporated entomophagy into Mexican haute cuisine, developing dishes that, although exotic and expensive to certain social strata, are nevertheless increasingly more acceptable and consumed in different restaurants and markets.However, it must be emphasized that even with the number of species registered in the state, anthropo\u2013entomophagy is not very popular in the big cities and municipal heads; they used to be consumed in rural zones in which they are collected, prepared, and eaten; likewise, we observed that this activity is very much appreciated by the elders and ignored by the young. This is due to the large quantity of modern foodstuffs which the latter tend to consume as part of their diets.Finally, we can say that this pre-Columbian legacy prevails, and we ascertain that edible insects are an essential part of our alimentary culture and an element of identity that generates nutritional, medicinal, and economic benefits to those that practice entomophagy in the Mexican Republic.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Both authors participated in the field research, writing, and final review of the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The Hiram J. Friedsam Award lecture will feature an address by the 2020 award recipient, Karen Kopera-Frye, PhD, MPA, FGSA, FAGHE. Hiram J. Friedsam was the professor, co-founder, and director of the Center for Studies in Aging and dean of the School of Community Service at the University of Northern Texas. Dr. Friedsam was an outstanding teacher, researcher, colleague, and mentor to students, faculty, and administrators, as well as a past president of AGHE. The purpose of this award is to recognize those who emulate Dr. Friedsam\u2019s excellence in mentorship."} +{"text": "Funding statement. The correct number for BMBF e:bio3 initiative HotSySAPP is 031L0078A. The corrected Funding statement appears below:In the original article, there was an error in the BSi acknowledges the funding by the Federal Ministry of Education and Research (BMBF). LS and SK received funds within the e:bio3 initiative HotSySAPP (031L0078A). LS acknowledges funding by MERCUR Pr-2013-0010.Author Contributions Statement appears below.Additionally, Roland Wohlgemuth was not included as an author. The corrected SK, LS, TB, KB, EA, RK, and RM performed the experiments. CB, BSi, BSc, MO, and SK wrote the manuscript, which was edited by CB and BSi. CB, RW, and BSi conceived the study. All authors approved the final manuscript.Conflict of Interest statement is as follows:The corrected BSc, RM, MO, KB, RK, EA, and RW were employed by the company Member of Merck Group, Sigma-Aldrich Production GmbH, Buchs, Switzerland.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Correction to: Cell Death & Disease10.1038/s41419-019-2214-9, published online 16 January 2020In the original published version of the article, there was a mistake in the affiliations:The first affiliation should read \u201cDivision of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China\u201dThis has been corrected in both the PDF and HTML versions of the Article."} +{"text": "At the European scale, the most studied topics were related to the environment, food, chemicals, pigments, protein, feed, and drugs. The highest scientific trends and market opportunities analysis identified bioplastics and biostimulants as top emerging concepts at the European level and agricultural, animalfeed, and bluebiotechnology at the European AA level. A bibliographic database of scientific papers published by authors affiliated worldwide, especially focused in Europe and in the European Atlantic Area, and containing the keywords \u201cmicroalga(e)\u201d or \u201cphytoplankton\u201d was built. A corpus of 79,020 publications was obtained and analyzed using the Orbit Intellixir software to highlight the evolution of the research domain. Publication rates from 1960 to 2019, organization of the research, collaboration networks between countries and organizations, emerging and fading research concepts, major studied species, and associated concepts, as well as journals publishing microalgae research were considered. As a result, of the 79,020 papers published worldwide, 26,137 included authors from Europe (33% of world production) and 6989 from the European Atlantic Area (AA) . The main worldwide scientific research topics found in this study were Microalgae, with an estimated number of 30,000 to 1,000,000 species, constitute a vast group of microorganisms extensively studied for their ecological functions in marine and freshwater environments and possible use as a source of feed, food, cosmetics, biofuels, nanomaterials, and pharmaceuticals ,3. SinceIn 2018, the scientific production reached 5747 publications per year in the world, 1806 (31% of the world production) publications per year in Europe, and 509 (28% of the European production) publications per year in the AA. From the results explained above, it can be noted that Europe and the European AA follow roughly the same publication trend as the world trend. An increased interest of the scientific community in microalgae can be noticed since 2005, as demonstrated by the rapid increase in the world and European publication rates and the important inflection of the publication slope, as highlighted by Garrido-Cardenas et al. (2018). These authors estimated that a 15-fold acceleration of the publication rate was observed after 2005 [Concerning European countries, the United Kingdom, France, Germany, Spain, and Italy were the main European countries producing scientific publications in the field of microalgae worldwide, with 5818, 5448, 5248, 4106, and 2925 publications, respectively. The five countries of the European AA were among the seven that published the most with co-authors in the AA. In this top seven, the U.S. and Germany published 836 and 494 scientific publications, respectively, with co-authors from the European AA. phytoplankton, community, bloom, diatoms, distribution, ecosystem, coastal, chlorophyll, zooplankton, photosynthesis, and primary production. This environment/phytoplankton research domain can be differentiated from the microalgae/high-added-value molecules field that contained less and more recent publications, as previously reported [reported . Feed was the predominant emerging concept for the three geographical areas, with a very high growth factors (GF) compared to the rest of the emerging concepts [hnology) .The 28 countries of the European Union produced 26,137 publications in the field of microalgae and phytoplankton; these papers are analyzed in detail in this section.Within the European Union, countries producing the largest number of publications are France (5445), Germany (5258), Spain (4100), Italy (2852), Netherlands (2353), the United Kingdom (2030), Sweden (1654), Denmark (1446), Poland (1192), Belgium (1189), Portugal (1164), and Finland (904). In addition, between 400 and 600 scientific publications have been published by Greece (556), the Czech Republic (555), Austria (484), and Ireland (416). The production of scientific publications was lower for Switzerland (348), Croatia (343), Hungary (338), and Estonia (319). Regarding the number of scientific papers published until 2019 for the 15 top publisher countries in Europe, France and Germany were the first to produce an important number of publications in Europe, with 100 publications per year since 1996 and 1997, respectively. Spain reached 100 publications per year in 2001, and the U.S. and Italy produced 100 per year in 2007. The number of scientific publications per country continues to increase each year. The city of Paris produced more than 50 scientific publications per year since 2007 and reached more than 100 publications per year since 2017. Wageningen, Lisbon, Kiel, and Barcelona each produced 50 scientific publications per year since the year 2000.environment, with 8962 publications, dominating the domains related to food and chemicals that contain 4275 and 4271 publications, respectively. These keywords cover very broad topics and more specific markets have fewer publications (less than 2000 publications). For example, many publications have been produced in Europe in the field of pigments (1861), proteins (1847), feed (1818), drug (1474), biofuel (1014), and biotechnologies (892). biostimulant (13), bioplastic (14), vaccines (16), biofertilizers (22), and nanotechnology (59).Hydrobiologia was the top publisher in Europe, with 1162 publications and an impact factor of 2.165. The majority of these journals relate to environmental/phytoplankton research and have impact factors ranging from 1.897 to 4.61 for an average of 2.69. The main journals related to the microalgae/high-added value molecules field are Bioresource Technology and Algal Research, with impact factors of 5.807 and 3.745, respectively.Chlorella sp. is the most published genus with almost twice as many publications as Scenedesmus sp. (733) and Chlamydomonas sp. (641). For each of genera, the corresponding emerging concepts are listed in Chlorella sp., the top emerging concepts were biostimulant and agro industrial waste species).Chlorella sp. in Following the identification of the top 15 microalgae genera studied in Europe, a detailed study of associated and emerging concepts, scientific consortia working on these genera in Europe, research cities, temporal evolution of publications by country, top journals, citations, and top cited papers was performed. The results of this advanced analysis are presented below for https://www.enhancemicroalgae.eu/). To compare on a global scale, 9% of world publications came from the AA, 15% of world authors were from the AA, and 37% of affiliations working in the field of microalgae were located in the AA. In this section, the AA was compared with Europe for (i) the main concepts and topics of scientific publications, (ii) the national contribution to publications, (iii) the networks of collaborations by city and country, as well as (iv) the main journals and citations in the field of microalgae. The EnhanceMicroalgae project is a transnational and inter-regional Atlantic project that aims to evaluate the potential of the European AA in the microalgae industrial sector (https:/biofuel (+55 publications), drug (+54), health (+44), and bioremediation (+31). In contrast, research topics such as environment (-58), biogas (-30), protein (-29), and chemicals (-26) were less published in the AA as compared to the European average. Other research fields ranging from +10 to -10 are in line with European research priorities , Italy (325), Germany (322), and France (310), followed by Portugal, the Netherlands, the U.S., Belgium, and the United Kingdom that have published each between 100 and 150 publications on microalgae high added-value molecules since 2017. The major AA cities working in this field are Wageningen, Paris, Rome, Lisbon, Barcelona, Almeria, and Nantes with 85, 66, 64, 63, 58, 57, and 50 publications including at least one co-author in the AA, respectively. As shown in microalgae/biomass/growth/cell/concentration. By dismissing these ubiquitous concepts, a network of 18 clusters was created in which model, treatment, acid, lipid, chemical, energy, nutrient, cultivation, green and carbon were the dominant concepts are concepts .Regardless of their size, the contribution of each country for publications in the AA, namely, Ireland, the United Kingdom, France, Spain, and Portugal, was compared in this section. The United Kingdom mainly contributed to these publications, as the United Kingdom affiliations were identified in 33% of the publications compared to 25% and 24% for France and Spain, respectively. Portugal produced 15% of the scientific publications in the European Area and Ireland was associated with 5% of the publications .The international scientific collaborations of the European AA were analyzed in this section in order to highlight strong collaborations but also to identify collaborations that could be developed for a better sharing of research at geographical and thematic levels. Marine Ecology Progress Series, Estuarine Coastal and Shelf Science, and Journal of Plankton Research with 263, 209, and 193 publications, respectively. As observed in the European database, the journals publishing the highest number of microalgae AA studies are related to environmental/phytoplankton research. The main journals publishing papers related to microalgae/high-added value molecules are Bioresource Technology and Algal Research-Biomass Biofuels and Bioproducts, with impact factors of 5.8 and 3.7, respectively, and Progress in Oceanography (IF 4.27). Despite the dominance of environmental science journals, the two scientific publications with the highest citations in the AA deal with the production of high-added value molecules from microalgae and are entitled \u201cMicroalgae for biodiesel production and other applications: A review\u201d and \u201cBiofuels from microalgae-A review of technologies for production, processing and extractions of biofuels and co-products\u201c. These papers were published in 2010 and cited 2610 times and 2124 times, respectively , Germany, Italy, and the Netherlands (particularly from Wageningen).A bibliographic database was built through a literature search performed in February 2019 including all reports published to date. The use of the Scopus database was compulsory to obtain a format compatible with the bibliometric analysis using the Orbit Intellixir software. The keywords \u201cmicroalgae\u201d and \u201cphytoplankton\u201d were used to list world publications, European publications , and European publications including at at least one author from the Atlantic regions of Portugal, Spain, France, the United Kingdom, and Ireland, as defined in the interregional (Interreg) AA research programs . The keyThe bibliographic database was last updated in February 2019 and it contained 79,020 publications, 111,975 authors, 4446 affiliations, and 931,299 concepts. These references are available on demand to the corresponding author.P being the number of cumulative scientific publications containing the concept at one time.A \u201cconcept\u201d designates a word (or group of words) present in the title, summary, or keywords of a publication that can be extracted and identified using a bibliometric software. The occurrence of a concept is the number of documents containing this concept, and co-occurrence the number of documents linking several concepts. The bibliographic database, including references without duplicates, was imported from Scopus (Editor Elsevier) into the Orbit Intellixir bibliometric software and analyzed to quantify the scientific production per year, country, organization, and annual evolution of publication rates. Collaboration networks between countries; public and/or private organizations; as well as major, fading, and emerging research concepts, were graphically represented using the most relevant formats available in the Orbit Intellixir software. Data were analyzed to highlight the latest trends in research topics; identify the most explored research concepts; point out the most studied species; and highlight strengths, opportunities, and collaborations in the research organizations from the European AA. Emerging concepts were defined as concepts that showed the greatest increase in frequency of use in the database over the last 2 years. A manual selection of emerging concepts was performed, as some of them were relevant for our study , whereas others were less . A growth factor (GF) was calculated to highlight the concepts with the highest emergence over the past 2 years (2017-2019). GF was calculated as Equation (1).phytoplankton, community, bloom, diatoms, distribution, ecosystem, coastal, chlorophyll, zooplankton, photosynthesis, and primary production. Focusing at the European AA level in which the Interreg EnhanceMicroalgae project is positioned, the analysis of the 6989 publications revealed that the biofuel, drug, health, and bioremediation topics are more published than at the European average. The major publishers of these AA publications were located in the United Kingdom, France, and Spain, particularly in research poles of Southampton, Vigo, Plouzan\u00e9, Lisbon, Brest, Nantes, and Plymouth. In contrast, compared to Europe, the AA produced less scientific publications in the field of microalgae-based high added-value molecules (1882 publications), suggesting a scope to extend in term of research, collaboration, and industrial development. The highest scientific trends and market opportunities were highlighted by identifying top emerging concepts such as bioplastics and biostimulants at the European level and agricultural, animal feed, and blue biotechnology at the European AA level. By focusing at the European scale, the most studied topics found in the 26,137 European publications were related to the environment, food, chemicals, pigments, protein, feed, and drugs. Analysis of international cooperation highlighted the strong links and partnerships with the United States, Canada, Norway, and Australia, but identified the possible development of new collaborations with most other countries. Within the European Union, France, Germany, and Spain dominated the scientific productivity, and the most studied and published species were Chlorella sp. and Scenesdesmus sp. A large number of microalgae and cyanobacteria species have received minimal attention, indicating a significant innovation potential for new molecules, new applications, and markets. Finally, this study provides an updated review of quantitative data at three different reading levels, and should allow microalgae stakeholders to guide their investments and projects for future research opportunities and cooperation in the field of microalgae research and bioeconomy.On the basis of the analysis of 79,020 publications at the world, European, and European AA levels, our study aimed to give a relevant overview of microalgae research until 2019, an in-depth analysis of research concepts and collaborations, and a European perspective on emerging topics. Studied microalgae species were also analyzed in detail to highlight their associated concepts, the networks of researchers working in the field, and the potential of development for new applications or new species. The scientific research topics were essentially the same at the world, European, and AA levels, with the main research concepts corresponding to"} +{"text": "Computer Vision Syndrome (CVS) has become a real problem during the past couple of years, as it appears in individuals due to prolonged computer, cell phone and tablet use. In addition, different associations, such as the Ontario Association of Optometrists (OAO) has recommended regular breaks, when looking at digital screens. It is already known that prolonged computer, cell phone and tablet usage may cause dry eyes, neck and shoulder pain, headaches, etc. All these eye problems may have as outcomes itchy eyes, blurred eyes and many other eye problems.In order to prevent these eye problems, a rule has been established by OAO, and that is, to look away from the screen every 20 minutes, for 20 seconds, and focus on something that is located 20 feet away. Consequently, optometrists advice adult individuals to close their eyes and daydream for 20 seconds. At the same time, children are recommended to look away and daydream on occasion, because, by doing so, they may prevent CVS, which includes affections, such as eye strain and burning eyes. The following tips are offered to prevent and reduce eye problems of kids: the height and setting of the computer should be checked; the glare on the computer screen should be checked, meaning that windows or other light sources should not be visible in the monitor; the amount of lighting in the room should be reduced to match the computer screen; continuous blinking is recommended.Provided that taking short 20 seconds breaks at every 20 minutes is almost impossible during a regular eight-hour work day, when most of the people spend their entire time staring into a screen, a Social Marketing campaign should also be implemented in Romania, with the aim to raise the awareness regarding this emergent modern \u201cdisease\u201d by bonding, bridging and linking the social issues and behavior change, and ensuring, in fact, a balance. Most of the times, Social Marketing campaigns are elaborated to assess a behavior change in a population, but are not going to be successful if certain strategies are not implemented. For instance, the determinants of a successful adopted health behavior depend on immediate environment conditions that encompass peers, local community, significant others and family, on wider social context elements such as societal norms, cultural symbolism, structural issues and social and economic conditions, and, in addition, on personal characteristics, with a specific interest in individual particularities, as goals, aspirations, self-efficacy, education, symbolic needs and skills.Fig. 1. In conclusion, I strongly believe that the efficient application of Social Marketing principles takes the shape of the Social Marketing\u2019s Value Triad, as illustrated in In Ophthalmology, it is acknowledged the fact that value is expressed subjectively and \u201cis in the eye of the beholder\u201d. Basically, it is important to refer to values because they are beliefs, ideas, experiences, emotions, and motivate actions and transcend to specific actions and situations. Assist. Prof. Gheorghe Consuela-M\u0103d\u0103lina, PhD,Philologist, Authorized translator"} +{"text": "This study explored the global cyberspace security issues, with the purpose of breaking the stereotype of people\u2019s cognition of cyberspace problems, which reflects the relationship between interdependence and association. Based on the Apriori algorithm in association rules, a total of 181 strong rules were mined from 40 target websites and 56,096 web pages were associated with global cyberspace security. Moreover, this study analyzed support, confidence, promotion, leverage, and reliability to achieve comprehensive coverage of data. A total of 15,661 sites mentioned cyberspace security-related words from the total sample of 22,493 professional websites, accounting for 69.6%, while only 735 sites mentioned cyberspace security-related words from the total sample of 33,603 non-professional sites, accounting for 2%. Due to restrictions of language, the number of samples of target professional websites and non-target websites is limited. Meanwhile, the number of selections of strong rules is not satisfactory. Nowadays, the cores of global cyberspace security issues include internet sovereignty, cyberspace security, cyber attack, cyber crime, data leakage, and data protection. Association rules, reflecting the interdependence and correlation between one thing and others, are one of the critical research methods in the data mining of graphic patterns . In otheRegarding the mining issues of association rules, Psychology was used to confirm the five personality traits, meta traits, and the hypothetical relationship between self-esteem and the legal network terminology network . AlthougAssociation-rule mining includes mining frequent item-sets and discovering strong association rules . Mining When association rules are mined from frequent item-sets, the method of using the \u201csupport-confidence\u201d model has been recognized by most researchers. In recent years, Based on the association rules of the Apriori algorithm in data mining, global cyberspace security was studied, to seek the focus of current cyberspace issues and to provide a path reference for future cyberspace governance . The proIt is essential to select appropriate target websites, thus ensuring the validity of the keywords database. Meanwhile, this study focused on target websites of global cyberspace security, which were divided into two types, professional and non-professional, to consider the comprehensiveness of data coverage.Professional websites include internet sovereignty, data breach, cyber attacks, and rogue software, involving multiple aspects of cyberspace security. However, non-professional websites are based on the information content published by mainstream news media. Although the content is relatively small compared to professional websites, it involves rich information about global cyberspace security.In the implementation of the first stage, professional websites and non-professional news websites were selected explicitly in global cyberspace security as the databases for lexicon selection. The ratio of the selected lexicon is generally maintained in a range of 1:1. A total of 15 target professional websites See and 25 nThe process of the first stage requires collecting lexicons to determine the necessary ones for the second stage of Python in the above website data crawler. As the basis for word segmentation, if the lexicons are not correctly selected, it is easy to miss critical data mining in the later analysis. This study selected 89 lexicons related to cyberspace security to cover all aspects of global cyberspace security, thus providing high-quality data for later association rules mining. The selected lexicons are listed as follows:Cyberspace governance, cyberspace security, system security, information dissemination security, information content safety, internet ecosystem, cyber infrastructure security, application security (application system security), Internet security, Internet of things security, transaction security, database security, mobile security, risk management, risk assessment, information disclosure, communication technology, cyber technology, cyber protocol security, cyber running security, local area cyber (cyber security inspection), computer viruses, information alterations (loss), media security, and environmental security, equipment security, cyber security inspection, communication cyber, global governance, artificial intelligence, security strategy, cyber attacks, cyber security vulnerability, cyber law, information security, cyber threat, strategic proposition, cyber supervision, coordination mechanism, emergency management, social cyber, monitoring and early warning, cyber risk, cyber crime, security specification, security prevention, data protection, business secret, cosmopolitan web, data service, security framework, data breach, security event, security threat, cyber intrusion, and cyber security crisis, international cooperation, security system, information technology, encryption technology, cyber pattern, ICANN, cyber competitiveness, cyber deterrence theory, cyber self-management, Internet governance, cyberspace sovereignty, national safety, information infrastructure, cyber-culture, cyber terror, cyber governance, fundamentals of cyber security, cyberspace protection, international cyber cooperation, personal information protection, critical information infrastructure, multi-stakeholders, digital economic cooperation, personal privacy protection, digital divide and poverty, international internet system, cyber ecological governance, internet governance, cyber rules, cyber laws, cyber sovereignty, and cyber monitoring.Association rules are similar to the implication expression of X \u27f9 Y, where X and Y are disjoint subsets, that is, X\u2229Y = \u00d8 . The strFor a given X \u27f9 Y, the higher the confidence, the greater the probability that Y is included in the transaction of X. Certainly, confidence can also estimate the conditional probability of Y at a given X . For exaApriori algorithm of a mining association rule is based on two core theories: the subsets of frequent item-sets are frequent item-sets, and the supersets of infrequent item-sets are infrequent item-sets . FrequenHowever, the Apriori algorithm uses an Iterative Method . First, The Apriori algorithm is used to find frequent k-item-sets, setting the minimum support to 50%. First, a candidate frequent 1-item-set is generated, including all five data and calculating the corresponding support. Secondly, pruning is performed after the calculation. Since the support of {cyber crime} 1-item-set is only 25%, it has to be cut off. Therefore, the final frequent 1-item-set, {cyber attacks, data breach, data protection, and artificial intelligence}, is linked to generate the candidate frequent 2-item-set, {cyber attacks, data breach), {cyber attacks, data protection}, {cyber attacks, artificial intelligence}, {data breach, data protection}, {data breach, artificial intelligence}, and {data protection, artificial intelligence}, with a total of six groups. The first round of iteration ends at this point.In the second round of iteration, the scanned data set is used to calculate the support of the candidate frequent 2-item-set, and then the item-sets are removed . The supData Breach \u27f9 Artificial Intelligence^Data Protection.Data Protection \u27f9 Data Breach^Artificial Intelligence.Artificial Intelligence \u27f9 Data Breach^Data Protection.Data Breach^Data Protection \u27f9 Artificial Intelligence.Data Breach^Artificial Intelligence \u27f9 Data Protection.Data Protection^Artificial Intelligence \u27f9 Data Breach.For the frequent item-set of {data breach, data protection, and artificial intelligence}, the subsets are {data breach}, {data protection}, {artificial intelligence}, {data breach, data protection}, {data breach, artificial intelligence}, and {data protection, artificial intelligence}. The rules are as follows:Therefore, based on the data mining of global professional and non-professional target websites, the Apriori algorithm is used to analyze association rules. Combining this association rule with a series of attributes can present the specific information content of cyberspace security on global professional and non-professional target websites, which marks the completion of mining association rules for transaction databases at the third stage.The specific presentation of global cyberspace security issues is based on the association rule of the Apriori algorithm. The confidence formula of conf (I1->I3^I2) = support /support (I1) is used to calculate the confidence of each rule. Then the minimum confidence and minimum support are compared to mine the strong rules corresponding to the data .However, the value of the corresponding rule can be analyzed through a series of attributes of association rules. (1) Support representing the support of the union of the former and the latter items ; (2) ConAfter the statistic of word segmentation and word frequencies of professional and non-professional target websites involved in global cyberspace issues, the Apriori algorithm is used to mine association rules and set threshold based on word frequency results. As a result, a series of association rules greater than the minimum support, and minimum confidence is obtained. Meanwhile, the patterns of LHS and RHS of association rules show the relationship among different word frequencies . The rulMeanwhile, the rule has an essential attribute of support, which indicates the frequency of rules occurring in this data set. The larger the threshold is, the more frequently the rule occurs . If bothMeanwhile, the lifts of LHS and RHS of 32 strong rules higher than the threshold are both greater than one, indicating the positive correlation of word frequency between the two items. \u201cInternational rule-making \u27f9 information technology\u201d and \u201cinternational cooperation and cyber attacks \u27f9 Information technology\u201d have the highest lifts, which are 8.55296 and 8.51475, respectively. Information technology is mentioned most frequently by international rule-making, international cooperation, and cyber attacks in the field of global cyberspace security. Moreover, the leverages of LHS and RHS of the 32 strong rules are both more than zero, showing that the word frequency cohesion between the two items is higher than expected. The strong rules with the closest relationship are \u201ccyberspace governance \u27f9 cyber sovereignty,\u201d \u201ccyber sovereignty \u27f9 cyberspace security\u201d and \u201ccyberspace security and cyberspace governance \u27f9 cyber sovereignty,\u201d the values of which are 0.11173, 0.10966, and 0.10807, respectively. Results show that cyberspace governance, cyber sovereignty, and cyberspace security in global cyberspace security have been mentioned and concerned frequently. However, \u201ccyberspace security and security governance \u27f9 cyber sovereignty\u201d has the highest conviction among the 32 strong rules, which is 22.71992, the same as the maximum value of lift. The independence of \u201ccyberspace security and security governance\u201d and \u201ccyber sovereignty\u201d is strong and closely related, which are mentioned almost simultaneously.When any word frequency of \u201ccyber sovereignty\u201d or \u201cartificial intelligence and cyber sovereignty\u201d appears, cyberspace security has a high probability of appearing. When the word frequencies of \u201ccyberspace security and information technology,\u201d \u201cnational security and cyberspace governance,\u201d \u201cpersonal information protection,\u201d and \u201csecurity threats and cyber attacks\u201d appear as LHS, \u201cinformation security\u201d frequently appears as RHS. After the appearance of \u201ccyberspace security and information technology,\u201d \u201cnational security and cyberspace governance,\u201d \u201cpersonal information protection,\u201d or \u201csecurity threats and cyber attacks,\u201d \u201cinformation security\u201d occurs, with the probabilities of 86.2, 85.3, 85.2, and 84.4%, respectively.Therefore, after comparing the Top 10 rules with the highest confidence and Top 10 rules with the highest support of global target professional websites, this study can obtain the following conclusions.Firstly, although \u201ccybercrime and international cooperation \u27f9 Internet governance\u201d does not appear in the Top 10 rules of support, it has the fifth-highest confidence. As long as cybercrime and international cooperation are mentioned in global professional target websites, there is a high probability of \u201cInternet governance\u201d appearing. Moreover, \u201ccyber sovereignty \u27f9 cyberspace security\u201d rank high in both the Top 10 support rules and the Top 10 confidence rules, which mean cyber sovereignty and cyberspace security are often mentioned by the international community in global professional target websites. Meanwhile, cyberspace sovereignty is mentioned as information about cyberspace security.The lifts of LHS and RHS of 27 strong rules higher than the threshold are both greater than 1, indicating the negative correlation of word frequency between the two items, and the relationship of mutual promotion is not significant. Moreover, the leverages of LHS and RHS of the 27 strong rules are both more than zero, showing that the word frequency cohesion between the two items is higher than expected. The strong rules with the closest relationship are \u201cCyber sovereignty \u27f9 Internet governance,\u201d \u201cCyber attacks \u27f9 Artificial intelligence,\u201d and \u201cCyber attacks \u27f9 Cyber crime,\u201d the values of which are 0.11166, 0.09816, and 0.07866, respectively. Results show that the international community generally pays attention to artificial intelligence, cyber sovereignty, cyber attacks, cyber crime, and Internet governance in the non-professional websites of global cyberspace security issues. \u201cCyber sovereignty \u27f9 Internet governance\u201d has the highest conviction among the 27 strong rules, which is 3.44828, while the maximum lift is the same as the maximum value of confidence. The independence of cyber sovereignty and Internet governance is strong and closely related, which are mentioned almost simultaneously.Therefore, this study compared the strong rules of professional and non-professional websites as a whole. Firstly, cyber sovereignty is widely concerned by people. Among professional websites, the strong rule of \u201ccyber sovereignty \u27f9 cyberspace security\u201d has the highest support, with the support of about 13.5%. In non-professional websites, \u201cInternet sovereignty \u27f9 Internet governance\u201d is the tenth rule order by support, with the support of about 13.6%. Secondly, from the perspective of confidence, the word frequency of cyber sovereignty is usually accompanied by cyberspace security, cyberspace governance, artificial intelligence, and information technology in professional websites. Finally, based on confidence, the word frequency of cyber sovereignty is only accompanied by Internet governance in non-professional websites. For the same LHS, there are more diverse RHS in professional websites, but it is single in non-professional websites, showing that cyber sovereignty has been studied more comprehensively in professional websites.1. 2. Through analyzing the data mining accuracy in global professional and non-professional target websites, namely, the ratio of the number of websites with cyberspace security to the total number of websites, the following can be found.According to the statistics of word segmentation on the data mining of global target websites, the word frequency results can be generated into the word cloud of professional and non-professional target websites. If the word cloud appears more frequently in cyberspace, the larger the font size of the word, the more pronounced the problem will be. Data breach, cyber sovereignty, Internet governance, information security, cyberspace security, national security, data protection, and cybercrime repeatedly appear in target professional websites, showing that the word frequencies involved in cyberspace security issues are professional and in-depth. However, the word frequencies of cyber sovereignty, cyber attacks, cybercrime, internet governance, security threat, computer virus, cyberspace security, cyber threat, artificial intelligence, and emergency management appear frequently in target non-professional websites. It shows that the mainstream news sites of the international community have only reported extensively on cyber security issues, lacking detailed and in-depth understanding.Through comparing the word frequencies that often appear in target professional and non-professional websites, although the perspective of cyberspace security issues is different, the two types of websites focus on cyber sovereignty, cyber attacks, cyberspace security, Internet governance, national security, data breaches, and cyber threat.Through sorting the word frequencies of global professional and non-professional target websites, the Top 10 strong rules of cyberspace security words with high frequency were obtained. If the proportion of word frequencies of the first 10 words is larger, the higher the ranking of the word is, the more frequently it is presented in global target websites, and the more it will be valued and recognized.The frequent words of the Top 10 strong rules of global professional and non-professional target websites are compared to find that the frequent words of professional target websites are more evenly distributed. In contrast, those of the non-professional websites are unevenly distributed with cyber attacks in a dominant position.Moreover, the word frequencies of global non-professional target websites are relatively broad, which are not as specific and accurate as that of professional websites. When presenting news related to cyberspace security, non-professional websites tend to use a single word frequency of cyber attacks. Conversely, professional websites use more specific and comprehensive words, adopting data breach, cyber sovereignty, information security, Internet governance, cyberspace security, and cyber attacks.There are differences in cultural traditions and ideologies in different countries on the global Internet, which have pervaded the whole cyberspace. Moreover, cyberspace security issues have attracted worldwide attention. This study analyzed association rules based on the Apriori algorithm. Besides, the association rules were studied by selecting 15 professional target websites and 22,493 web pages, of which 15,661 websites are related to cyberspace security, accounting for 69.6% of the total target professional websites. A total of 25 non-professional target websites and 33,603 web pages are selected. Among them, 735 websites mention cyberspace security, accounting for 2% of the total number of non-professional websites. According to the threshold set by Python, the minimum support is 0.01, and the minimum confidence 0.05, with a total of 181 strong rules mined.The 32 strong rules for the professional target website and 27 strong rules for the non-professional website are listed above. Moreover, the other strong rules are not analyzed due to their low importance and low research value. The two types of target websites cover China, America, Britain, Germany, France, India, and other developed and developing countries on the Internet. The results reflected the interdependence and correlation among global cyberspace security issues.After the word clouds of global professional and non-professional target websites are compared, professional websites focus on the Top 10 high-frequency words containing a data breach, cyber sovereignty, information security, Internet governance, cyberspace security, cyber-attacks, cybercrime, data protection, national security, and cyber threat. Global non-professional websites, namely the mainstream news website of the international community, focus on the Top 10 high-frequency words of cyber attacks, cyber sovereignty, Internet governance, cybercrime, cyberspace security, artificial intelligence, data breach, national security, data protection, and cyber threats.The limitation of the work lies in the limited number of data mining samples due to different language restrictions for global professional and non-target websites, which leads to an insufficient selection of strong rules. In future research, the following aspects will be completed: breaking through the language bottleneck, highlighting the number of selected data with strong rules, and taking mainstream countries as the target samples. A single country will be taken as a sample to analyze professional and non-professional websites involving cyber security issues. After concluding, the focus on cyber security issues between countries will be compared.Through comparing the word frequencies, the professional and non-professional target websites focused on cyber sovereignty, cyber attack, cyberspace security, Internet governance, national security, data leakage, and cyber threats. After sorting the word frequencies of global target professional websites and non-professional websites separately, the high word frequencies of the Top 10 strong rules of professional websites were data breach, cyber sovereignty, information security, Internet governance, cyberspace security, cyber attacks, cyber crime, data protection, national security, and cyber threats. Meanwhile, the high word frequencies of the Top 10 strong rules of non-professional websites were cyber attacks, cyber sovereignty, Internet governance, cyber crime, cyberspace security, artificial intelligence, data breach, national security, data protection, and cyber threats. Therefore, the focuses of current global cyberspace security issues were cyber sovereignty, Internet governance, cyberspace security, cyber attacks, cyber crime, national security, cyber threat, and data protection.From an industry perspective, the first level of focus referred to data breach and cyber sovereignty. The second was Internet governance, information security, cyberspace security, architectural security, data protection, cyber crime, and cyber attacks. The third referred to cyber threat, artificial intelligence, application security, security threat, physical cyber security, and cyber risk. The fourth refers to security strategy, information technology, multi-stakeholder, Internet security, risk assessment, infrastructure security, and international cooperation.In terms of the international community, the first level included cyber sovereignty and cyber attacks. The second included Internet governance, cybercrime, data protection, security threats, data breach, cyberspace security, emergency management, national security, security strategy, and security system. The third includes computer viruses, cyber risks, artificial intelligence, information security, international cooperation, ICANN, risk assessment, security incidents, trade secrets, and infrastructure security. The fourth includes Internet security, global governance, cyber monitoring, communication technology, cyber law, cyber technology, and system security.Based on this level analysis, this study sorted out the security issues in global cyberspace, and summarized the specific security problems in cyberspace. It showed that the global cyberspace security issues were different from the identification of the international community. For the global governance of cyberspace security, effective and targeted governance solutions can be proposed according to this study, which is conducive to building a community with a shared future in cyberspace and constructing an Internet governance system.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Zhejiang University and Dalian University of Foreign Languages Ethics Committees. The patients/participants provided their written informed consent to participate in this study.ZL designed the study, conceived the analysis question and conducted the analysis; XL and LZ conducted the analysis also and critically revised the manuscript content; and RT is the organizer of the project and responsible for sorting out the contact data and connecting with other researchers.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the published article, there was an error in affiliations 1 and 2. Instead of \u201cRoche Pharmaceutical Research & Early Development\u201d, it should be \u201cRoche Pharma Research & Early Development\u201d.Conflict of Interest section. Author ownership interests were omitted from the Conflict of Interest.In the original article, there was an error in the A correction has been made to the Conflict of Interest section:The authors declare that this study received funding from F Hoffmann-La Roche Ltd. The funder had the following involvement with the study: study design, generation of the molecules tested in the study, data collection and analysis, decision to publish, and editorial support for the preparation of this manuscript. All authors are employees of F Hoffmann-La Roche Ltd. Authors JS, SC, TF, AR, MBi, LF, TN, AS, MLC, CK, PU, and MBa hold stock/stock options for F\u00a0Hoffmann-La Roche Ltd and authors JS, SC, TF, VG-N, MP, TN, AS, CK, PU, and MBa hold patents related to the TCB technologies reported in the manuscript.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-019-40025-7, published online 13 March 2019Correction to: In this Article, the authors neglected to include some professional collaborations that may be perceived as potential conflicts of interest. The Competing Interests section should read:\u201cIn their capacity as Government of Canada research scientists, MP.P. and K.A.G. have had recent or ongoing collaborations with the following institutions that have the potential to be financially affected by the findings of this study: British Columbia Centre for Aquatic Health Sciences, British Columbia Salmon Farmers Association, Canadian Food Inspection Agency, Centre for Aquaculture Technologies Canada, Centre for Coastal Health, Cermaq Canada, Freshwater Fisheries Society of British Columbia, Grieg Seafood, Mowi Canada West, New Jersey Division of Fish and Wildlife, Northwest Indian Fisheries Commission, Norwegian Veterinary Institute, Okanagan Nation Alliance, Pacific Salmon Commission, United States Geological Survey, and the Washington Department of Fish and Wildlife. These institutions did not provide financial support for this study, participate in its experimental design, contribute to data collection, analysis, interpretation, preparation of the manuscript, or decision to publish. All authors declare they have no commercial interests with relevance to this work.\u201d"} +{"text": "Specifically, the work institute should have been featured as \u2018Department of Neurosurgery, The Third People's Hospital of Pingdu City\u2019 and the zip code should have been presented as \u2018266753\u2019. The corrected author affiliation details for this paper are shown below.1, SHOUKE GENG2 and YUANLI DA3BAOSHAN LI1Department of Neurosurgery, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041; 2Department of Neurosurgery, The Third People's Hospital of Pingdu City, Qingdao, Shandong 266753; 3Department of Neuro-Rehabilitation, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041, P.R. ChinaAll the authors agree to this Erratum, and the Editor apologizes to the authors for the inconvenience caused."} +{"text": "A challenging frontier in modern statistical physics is concerned with systems with a small number of degrees of freedom, far from the thermodynamic limit. Beyond the general interest in the foundation of statistical mechanics, the relevance of this subject is due to the recent increase of resolution in the observation and in the manipulation of biological and man-made objects at micro- and nano-scales. The peculiar feature of small systems is the role played by fluctuations, which cannot be neglected and are responsible for many non-trivial behaviors. The study of fluctuations of thermodynamic quantities, such as energy or entropy, goes back to Einstein, Onsager, and Kubo; more recently, interest in this matter has grown with the establishment of new fluctuation\u2013dissipation relations, which hold even in non-linear regimes, and of the so-called stochastic thermodynamics. Such a turning point has received a great impulse from the study of systems that are far from thermodynamic equilibrium, due to very long relaxation times, as in disordered systems, or due to the presence of external forcing and dissipation, as in granular or active matter. Applications of the thermodynamics and statistical mechanics of small systems range from molecular biology to micro-mechanics, including, among others, models of nano-transport, of Brownian motors, and of self-propelled organisms.entropy production and stochastic thermodynamics (8);heat transport and entropy in nonlinear chains and long-range systems (4);granular and other dissipative systems (2);phase transitions and large deviations in probabilistic models (2);coarse-graining techniques (2);ferromagnetic models (2).In this special issue, we collect 20 contributions, spanning the above mentioned subjects. In particular, the main addressed topics are as follows:In , the stoIn , the intIn , the posIn , the proIn , the autIn , a magneIn , two intIn , a stochIn , transpoIn , a multiIn , the effIn , the relIn , the intIn , the traIn , an examIn , a stochIn , a systeIn , spatialIn , the autIn , the spi"} +{"text": "Raymond Victor Downing was born on 16 February 1949 in Massachusetts, USA. He was the second of three children born to Harry and Ebba Downing. He was brought up in the Plymouth Brethren church in Auburn, Massachusetts, and lived in Massachusetts for his early childhood. In 1967, he went to Tufts University, and in 1975, received his Doctor of Medicine (MD) from New York Medical College. Afterwards, Raymond completed his residency in Family Medicine at the University of Tennessee Hospital and worked in Tennessee for 7 years. He met Dr Janice Armstrong, also a family physician, during his stay in Tennessee and they married in October 1977. There they had two children: Elizabeth and Timothy.In 1985, they moved with their two young children to Sudan to work in a refugee settlement clinic. From there, in 1989, they moved to Tanzania to work in a Mennonite Mission Hospital. Four years later in 1994, they moved again to Kenya, and began working at Friends Lugulu Hospital in western Kenya. In 2005, Raymond and Janice joined the Department of Family Medicine, Moi University in Webuye, Bungoma County., and worked with other colleagues to design the first family medicine training programme in the country. In 2016, Raymond retired from Moi University, and shortly afterwards joined the medical team at Dreamland Mission Hospital, where he worked until his death.Such a Time of It They Had and Global Health Means Listening. He was a devout Christian, a family medicine physician, mentor, author, teacher, brother, father, husband, colleague and a great friend.Raymond was also a prolific writer and has written several books and essays on global health and medicine, which include his thoughts on death and dying. His most recent titles include Raymond passed away comfortably on Monday, 20 January 2020, in the evening at his home in Kimili, western Kenya surrounded by his entire family. He leaves behind his wife, Janice Armstrong; two sisters, Mary-Ellen Welsher and Nancy Kline; and two children, Elizabeth and Timothy Downing. He would certainly be missed."} +{"text": "We regret any confusion or inconvenience this error may have caused.In the article, Oral Health and COVID-19: Increasing the Need for Prevention and Access, the degree designations were omitted for Jane A. Weintraub, DDS, MPH. The author byline was corrected on August 14, 2020, and the article appears online at"} +{"text": "Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity , and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process. Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity are well-established markers of normal brain maturation \u20135 and agMore recently, peak width of skeletonized mean diffusivity (PSMD) , a new pTen independent data sets coming from cross-sectional cohort studies were gathered in the present study, namely, MRi-Share, BIL&GIN, SYS, LIFE-Adult, 1000 BRAINS, UKBiobank, ASPSF, OATS, LBC1936, MAS (see acronym definition in http://www.psmd-marker.com) . This orker.com) , 24, usiDue to previously reported non-linear effects of age on DTI metrics , 3, 8, wFor each of the five DTI metrics and each age category, we performed an analysis of variance including \u201cage\u201d as the main effect, and \u201csex,\u201d total intracranial volume (TIV), and \u201cCohort\u201d as confounding factors. The Cohort effect was included in order to account for apparent large differences in DTI metric average values across cohorts contributing to the same age category data set see , 25\u201328, For each of the five DTI metrics and each age category, we also performed an analysis of variance including \u201cSex\u201d and \u201cTIV\u201d as main factors and \u201cCohort\u201d as confounding factors.All statistical analyses were performed using the JMP Pro Software .The evolution of PSMD across the adult life is different from that of the other metrics (This apparent specific lifespan profile of PSMD was confirmed by the quantitative estimates of the effects of age on PSMD and other DTI metrics provided by the between-cohort ANOVA (see p < 10\u22124) in all cases but RD (p = 0.53).Amplitude of sex effects on DTI metric average values were found to be quite variable across the various cohorts for the different age categories , mean FA values were higher and diffusivity values were lower when averaged over the white matter skeleton than when averaged over the entire white-matter compartment. However, the cross-subject variability measured as the CV of the mean DTI metrics decreased only marginally (a fraction of a percent for CVs ranging from 2% to 4%) when mean values were computed over the white matter skeleton rather than the whole white matter. In contrast, the CV of PSMD decreased markedly when its computation was performed on the white matter skeleton rather than on than the global white-matter mask. This demonstrates the importance of choosing a measure of MD dispersion values over a white matter skeleton for controlling between subject variability.In the present work, we restricted the analysis to classical DTI metrics as only two of the contributing cohorts had high angular resolution and/or multi-shell acquisition schemes that could be used for estimating advanced white-matter microstructural parameters with more sophisticated models . Here, D2 = 6.7 \u00d7 10\u22123 for the sex effect to be compared with 7.6 \u00d7 10\u22122 for the age effect), which could explain the mixed findings in the literature, and suggests further investigations are required in order to understand their biological origins. TIV effects on DTI parameters are not well established in the literature. In our study, we found that TIV was positively correlated with all DTI parameters except for RD. Similar to sex, TIV effects when significant were very small . Here again additional investigations are needed to understand the origins of these effects.Mixed results have been reported regarding the impact of sex and TIV on DTI measures ) in a sample of healthy individuals aged 60 to 80 years drawn from the ASPF cohort The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.The 10 cohort studies involving human participants were reviewed and approved by the following ethic committees: Comit\u00e9 de Protection des Personnes Sud-Ouest (MRi-Share), Comit\u00e9 d\u2019Ethique de Basse-Normandie (BIL&GIN), Research Ethics Committee of the Chicoutimi Hospital (SYS), Ethics committee of the University of Duisburg-Essen (1000BRAINS), Ethics board of the Medical Faculty of the University of Leipzig (LIFE), North West Multi-center Research Ethics Committee (UKBiobank), Ethics Committee of the Medical University Graz (ASPS), Ethics committees of the Australian Twin Registry, University of New South Wales, University of Melbourne, Queensland Institute of Medical Research and the South-Eastern Sydney and Illawarra Area Health Service (OATS), Multi-Centre Research Ethics Committee for Scotland and the Lothian Research Ethics Committee (LBC1936), Ethics Committee of the University of New South Wales (MAS). The participants provided written informed consent to participate in these studies.Study conception: BM and SD. Data collection: GB, CT, SC, ZP, TP, RS, PS, HB, NK, JT, ID, AW, AV, and BM. Data analysis: GB, LPe, SC, JS, YP, LPi, PS, WW, NA, MB, SM, AW, MD, and BM. Drafting: GB, AT, and BM. Revising the manuscript: LPe, CT, SC, JS, ZP, YP, TP, RS, LPi, PS, WW, NA, ID, MB, JW, SM, AW, AV, MD, SD, and BM).www.jpnd.eu: Australia, National Health and Medical Research Council, Austria, Federal Ministry of Science, Research and Economy; Canada, Canadian Institutes of Health Research; France, French National Research Agency; Germany, Federal Ministry of Education and Research; Netherlands, The Netherlands Organization for Health Research and Development; United Kingdom, Medical Research Council. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 643417. This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under grant agreement No 640643.GB has been supported by an EU-ERC starting grant . AT is supported by a grant from the Fondation pour la Recherche M\u00e9dicale (DIC202161236446). SC was supported by the Initiative and Networking Fund of the Helmholtz Association and the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement 785907 (Human Brain Project SGA2). The BRIDGET project is supported by the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of SVD of the Brain) and is an EU Joint Program -Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND\u2014The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The correct affiliations are as follows: Barbara Saracino11 Department of Political and Social Sciences, University of Bologna, Bologna, Italy, 13 Department of Sociology, Universit\u00e0 di Trento, Trento, ItalyInformation is missing in the captions for Figs"} +{"text": "Noriko Nishikawa, of the medical division staff, for assistance with data collection.\u201dSubsequently to the publication of the above article, the authors have noted that the Abstract and the Acknowledgements contained errors and an omission, respectively, and wish to correct these points for the record. First, in the Abstract, on p. 191, the pair of consecutive sentences beginning on line 16 should have read as follows (changes highlighted in bold and in the subsequent parentheses): \u201cIn the non-fatty liver group, the odds ratio (OR) for hypertension was 1.73 . In the fatty liver group, the OR for each Mets-related diseases were as follows: Dyslipidemia, 0.64 ; impaired glucose tolerance, 0.57 ; chronic kidney disease, 0.58 ; and Mets by Japanese criteria, 0.63 . . Secondly, in the Acknowledgements section, \u201cNoriko\u201d should have been properly acknowledged as follows: \u201cThe authors thank all the members of the Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital. The authors would also like to thank The authors apologize for these errors, and for any inconvenience caused."} +{"text": "Phlorotannins are polyphenolic compounds produced via polymerization of phloroglucinol, and these compounds have varying molecular weights (up to 650 kDa). Brown seaweeds are rich in phlorotannins compounds possessing various biological activities, including algicidal, antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. Many review papers on the chemical characterization and quantification of phlorotannins and their functionality have been published to date. However, although studies on the safety and toxicity of these phlorotannins have been conducted, there have been no articles reviewing this topic. In this review, the safety and toxicity of phlorotannins in different organisms are discussed. Online databases were searched, yielding 106 results. Following removal of duplicates and application of the exclusion criteria, 34 articles were reviewed. Phlorotannins from brown seaweeds showed low toxicity in cell lines, invertebrates, microalgae, seaweeds, plants, animals , and humans. However, the safety and toxicity of phlorotannins in aquaculture fish, livestock, and companion animals are limited. Further studies in these organisms are necessary to carry out a systematic analysis of the safety and toxicity of phlorotannins and to further identify the potential of phlorotannins as functional foods, feeds, and pharmaceuticals. Phlorotannins are polyphenols found in brown seaweeds, consisting of phloroglucinol , phenyl linkage (fucols), ether and phenyl linkages (fucophloroethols), and dibenzodioxin linkage (eckols). Numerous phlorotannins have been discovered from brown seaweeds, including eckol ,4,5, phlompounds . In browompounds ,15,16.Eisenia bicyclis, E. arborea, E. cava, E. kurome, E. stolonifera, Pelvetia siliquosa, and Ishige okamurae, as well as from the genera Cystophora and Fucus, contain phlorotannins that possess antidiabetic, antioxidant, antitumor, anti-inflammatory, and anticancer properties , and humans (4 articles) at a moderate dosage. Mild side effects were recorded in humans, fish, and dogs. However, in other organisms, there was no toxicity from phlorotannins, which have various biological activities. These findings can be the basis for developing these compounds as novel functional foods, feeds, and pharmaceuticals. To date, to the best of our knowledge, no studies have been performed on the safety and toxicity of phlorotannins in aquaculture fish; livestock ; and companion animals (birds and cats). The safety, toxicity, and availability of phlorotannins in these organisms should be verified with further studies."} +{"text": "Aldo A. M. Lima and Pascal Bessong are not included in the author byline. Aldo A. M. Lima should be listed as the thirteenth author and affiliated with Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil. The contributions of this author are as follows: Conceptualization, Data Curation, Investigation, Methodology and Writing \u2013 Review & Editing. Pascal Bessong should be listed at the fourteenth author and affiliated with the University of Venda, Thohoyandou, South Africa. The contributions of this author are as follows: Conceptualization, Data Curation, Investigation, Methodology and Writing \u2013 Review & Editing."} +{"text": "In addition to protein, fatty acids and vitamins, hen eggs also contain many minerals, including macroelements, microelements and trace elements. Currently, many different organic mineral supplements are introduced into the diet of laying hens, which can affect the content of chemical elements in the albumen and yolk. These effects are not fully understood. In the present work, the effect of the addition of humic preparations to the standard feed mixture on the content of essential and non-essential chemical elements in albumen and yolk of hen eggs was assessed. The obtained results indicate that only some elements significantly increase in the albumen and yolk when more of them are in a feed mixture enriched with humic preparations.This study was conducted to determine the effect of dietary supplementation with two humic preparations, Humokarbowit (HKW) and Humobentofet (HBF), on the mineral content of the albumen and egg yolk of Lohmann Brown hens. The content of macroelements , microelements and trace elements in the feed mixture (FM), albumen and yolk were presented. The material was collected from laying hens kept in a cage system in two groups, control (C) and enriched (E), with standard feed and feed enriched with humic preparations, respectively. The enriched feed mixture was characterised by a significantly higher Ag, Ba, Be, Bi, Co, Fe, Ga, Hg, K, Mg, Ni, S, Sb, Si, Zn and Zr content compared to the standard, basal mixture. Only some of these elements were found in significantly increased levels in albumen and yolk . Another noteworthy finding was a significantly lower concentration of Na in the content of eggs from the E-Group, which corresponds to the content of this important macronutrient in the feed. In addition, a significant increase in the concentration of elements such as Al, I, Li, Sr, Ti, Tl, Y, W was noted with a reduction in Cd, Cr, Hg, Mn, Rb, Sn in Group-E, which indicates a complicated egg formation processes, including biotransfer-essential and non-essential chemical elements. Hen eggs are an important component of the human diet. Their physico-chemical and biological properties are quite well known, and in recent years their role as a source of nutraceutical and biomedical substances has increased ,2,3,4. IIt is known that hen eggs are a good source of iron (Fe), phosphorus (P) and sulphur (S). The eggs also provide calcium (Ca), chlorine (Cl), potassium (K) magnesium (Mg) and sodium (Na). Smaller amounts of ions include: silver (Ag), aluminium (Al), boron (B), barium (Ba), bromine (Br), cobalt (Co), chromium (Cr), copper (Cu), fluorine (F), iodine (I), lithium (Li), manganese (Mn), molybdenum (Mo), rubidium (Rb), selenium (Se), silicon (Si), strontium (Sr), titanium (Ti), vanadium (V), uranium (U) and zinc (Zn). Eggs may also contain heavy metals such as arsenic (As), bismuth (Bi), cadmium (Cd), mercury (Hg), lead (Pb), thallium (Tl) and others in trace concentrations ,10,11. R3 with atomic weights greater than 40.04 and are generally termed heavy metals. Theses metals include: Ag, Au, Bi, Ce, Cd, Cr, Co, Cu, Fe, Ga, Hg, Mn, Ni, Pb, Pt, Sb, Sn, Te, Tl, U, V and Zn. Some of these heavy metals such as Co, Cr, Cu, Mg, Fe, Mo, Mn, Ni, Se and Zn are essential nutrients that are required for various physiological and biochemical functions in the body, but may cause acute or chronic toxicities in large doses [Metals are ubiquitous in the environment and they can easily accumulate in biological organisms including plants and animals, in animal origin products such as eggs, milk, and meat. Among the 35 naturally existing metals, 23 possess high specific density above 5 g/cmge doses .A slightly different classification of elements is given by Lim and Schoenung . Heavy mThe mineral composition of hen eggs is genetically determined, but environmental (management) and nutritional factors can modify it to some extent ,21,22,23Evidence suggests that the mineral composition of feed mixtures, the origin and quality of nutrients and their chemical form and bioavailability have the greatest importance in the accumulation of essential and non-essential chemical elements in the hen\u2019s eggs ,25,26,27The aim of this study was to determine the effect of a feed mixture enriched with humic preparations on the concentration of essential and non-essential elements in the albumen and yolk of Lohmann Brown hen eggs.The feeding experiment on laying hens was approved by the Second Local Ethical Committee on Animal Testing at Wroclaw University of Environmental and Life Sciences .2 per hen) at 20 weeks of age and kept until the peak of laying (33 weeks of life). The feeding experiment was conducted for 90 days. The basal diet was formulated according to the nutrient recommendations for LB laying hens [A total of 60 Lohmann Brown (LB) laying hens were used in the experiment. Birds were housed in battery cages in a vivarium with a controlled climate and light programme (16L: 8D) located at the research station of UPWr in Swojec (Poland). Hens were put into cages (750 cming hens .Eggs for tests were collected at the peak of laying (approximately 95%) for 5 consecutive days from all 12 cages. Every day, 5 undamaged eggs with similar mass (62\u201366 g) were randomly selected from both groups (C and E). Then the eggs were broken and the albumen was separated from the yolk and stirred thoroughly in a glass vessel. Five samples of albumen and yolk were collected from each group (C and E) each day leading to 60 eggs being collected in total. The egg material was stored for 10 days in a cold storage room before being transferred to the chemical laboratory at the Wroclaw University of Science and Technology. Additionally, samples of feed mixtures (FMs) were collected from both groups every two weeks in an amount of approximately 0.5 kg each (n = 5) for chemical analysis.3 from Merck in a microwave oven . An inductively coupled plasma optical emission spectrometer with ultrasonic nebulizer and an inductively coupled plasma mass spectrometer ICP-MS (ICP-MS Varian UltraMass-700 Instrument) were used in the analysis of the content of essential and non-essential elements in the feed mixture and the egg content. The level of other elements was determined by ICP-MS, while the content of the remaining elements by ICP-OES. Mercury was measured directly in raw materials using an AMA-254 mercury analyzer . The analyses were carried out in the Multielemental Analyses Chemical Laboratory at the Wroclaw University of Science and Technology, which is accredited by International Laboratory Accreditation Cooperation/Mutual Recognition Arrangement and the Polish Centre for Accreditation (nr AB 696), according to PN-EN ISO/IEC 17025. The quality of analytical process was controlled with the certified reference material CRM 8415 EGG POWDER, NIST.All used chemicals were of analytical grade. Eggs from the two groups were collected and analysed for their element content by inductively coupled plasma optical emission spectroscopy (ICP-OES and ICP-MS). The specified mass of biological samples was digested in Teflon vessels with 5 mL of concentrated supra pure grade HNOp < 0.05 and p < 0.01.The analysis was carried out using Statistica ver. 13.1. The data were presented as the mean and standard error of mean (SEM). The normality of the distribution was assessed using the Shapiro\u2212Wilk test. If the distribution was normal, a Student\u2019s t-test for independent samples was performed. If the distribution was not normal, a Mann\u2212Whitney U test was carried out. Effects were considered significant at a probability of The results of the analyses of feed mixtures show somThe results of chemical analyses of the albumen and yolk from Group-C and Group-E are shown in Among the six macroelements, the level of S and Na was the highest in the albumen, while P, S and Ca were highest in the yolk. The maximum value observed in the albumen was from S (2114 mg/kg wet wt) and in the yolk was P (6032 mg/kg wet wt). The concentration of macroelements such as Mg, K and S in Group-E significantly increased the concentration of S in the albumen and K in the yolk. However, the reduced Na concentration in the experimental feed mixture significantly reduced the level of this important macronutrient in egg content in Group-E. Despite the differences in the concentration of these elements, they are within the ranges given by other authors ,20,35,36Among the eight microelements, Al and Si were the highest in the egg albumen, while Fe, Si and Zn were the highest in the yolk. The maximum value observed in the albumen refers to Si (6.86 mg/kg wet wt) and to Fe (81.8 mg/kg wet wt) in the yolk. The increased concentration of microelements, such as Ba, Si and Zn, in Group-E did not significantly affect the accumulation of these elements in egg content. The significant increase in Al concentration and decrease in Mn in the albumen, and the increase in concentration of Fe, I and Sr in the egg yolk from Group-E compared to Group-C, were noted. In relation to Cu, Fe, I, Mn and Zn, the obtained results are only partially consistent with data from other authors ,10,21,35Among the 23 trace elements tested, Ni, Rb and Ti were most abundant in the egg albumen, while Cr, Rb and Sn and were most abundant in the egg yolk. The most abundant element observed in the albumen and the yolk was Rb . The increased concentration in Group-E of trace elements, such as Ag, Be, Bi, Co, Ga, Hg, Ni, Sb and Zr, significantly influenced the accumulation of only Bi, Co and Ni in the albumen and Bi and Sb in the yolk. There was also a significant increase in Al, Tl and W in Group-E albumen and a decrease in Cd, Cr, Rb and Sb compared to Group-C. In the yolk, however, these relationships concern Li, Ti, Tl, Y and W (growth) and Hg and Sn (decrease). It is difficult to explain the significant increase in Tl in the content of eggs from Group-E when both FMs had almost identical concentrations of this toxic trace element. Thallium interacts with several elements, such as K, Rb and S, which may explain its accumulation in egg content, especially in the yolk ,37. TungThe other elements in both groups were observed in similar concentrations: in the albumen, Ag, As, Be, Ga, Hg, Li, Mo, Pb, Se, Sn, Ti, V, Y and Zr; and in the yolk, Ag, As, Be, Co, Cd, Cr, Ga, Mo, Ni, Rb, Pb, Se, V and Zr. It is worth adding that the content of the most toxic heavy metals, such as As, Cd, Hg and Pb, did not differ significantly between groups E and C. Some authors ,28 reporThe obtained results can be compared with others despite being implemented in other management conditions of laying hens (deep litter system). The authors used HKWSauropus androgynus) leaf extract (SALE) on the production parameters of laying hens and the quality and chemical composition of their eggs. The results showed that the SALE supplementation did not significantly affect levels of calcium, phosphorus, iron and potassium, even at high doses. The SALE contained 2330 mg calcium, 980 mg phosphorus and 35 mg iron in 1 kg.In other studies, the diet of laying hens was supplemented with soybean meals enriched with Cr, Cu, Fe and Zn. The results showed that the use of this feed additive in the diet of laying hens (Hy-Line Brown) influenced the transfer of microelements to eggs, in particular at increased dosing. Eggs were biofortified with Fe, Zn, and Cu and, to a lesser extent, Cr. Microelements accumulated mainly in the albumen. Transfer of trace elements to eggs was not linearly dependent on the dose of biologically bound microelements in the diet . This waThe content of trace elements in hen eggs (and other domestic birds) was analysed by Nisianakis et al. . Hens and reduced only the Na concentration. The effect of feeding this enriched mixture caused significant increases in elements such as Al, Bi, Co, Ni, S, Tl, W in the albumen and Sb, Bi, I, Fe, K, Sr, Li, Tl, Ti, W and Y in the yolk, while it significantly decreased concentrations of Sb, Cd, Cr, Mn, Rb , Hg and tin (yolk). Lower levels of Na in the experimental diet also significantly reduced the content of this important macronutrient in the egg content. From the point of view of the nutritional value of eggs, it is very important to obtain a significant increase in the content of Co, I, Fe, Ni, K, Si, S, W , while ensuring heavy metals (toxic) such as As, Cd, Hg, Pb or Tl do not exceed the values given by various authors. A full assessment of the legitimacy of the administration of humic preparations to laying hen diets must take into account studies on the physical characteristics of the eggs (shell thickness and strength) and their organoleptic characteristics, which will be the subject of upcoming work of the authors."} +{"text": "Using a test data set (n = 50), we defined the mean ratio of the maximum skin dose obtained from measurements with radio-photoluminescence glass dosimeters (RPLGDs) to the Total Ka,r as the conversion factor, CFKa,constant, and compared the accuracy of the estimated maximum skin dose obtained from multiplying Total Ka,r by CFKa,constant (Estimation Model 1) with that of the estimated maximum skin dose obtained from multiplying Total Ka,r by the functional conversion factor CFKa,function (Estimation Model 2). Estimation Model 2, which uses the quadratic function for the ratio of the fluoroscopy Ka,r to the Total Ka,r , provided an estimated maximum skin dose closer to that obtained from direct measurements with RPLGDs than compared with that determined using Estimation Model 1. The same results were obtained for the validation data set (n = 50). It was suggested the quadratic function for the Ka,r ratio provides a more accurate estimate of the maximum skin dose in real time.Understanding the maximum skin dose is important for avoiding tissue reactions in cerebral angiography. In this study, we devised a method for using digital imaging and communication in medicine\u2014radiation dose structured report (DICOM-RDSR) data to accurately estimate the maximum skin dose from the total air kerma at the patient entrance reference point (Total K The advances in interventional radiology (IVR) technology in recent years have resulted in an increased number of patients undergoing lengthy procedures, and the increased radiation exposure of patients is becoming a great concern. Although neurointerventional radiology (NIR) has a number of practical benefits for patients, including being less physically invasive than surgical treatment and requiring a shorter time in hospital, there have been numerous reported cases of tissue reactions (deterministic effects), such as hair loss, under increased radiation exposure doses ,2,3,4,5.skin,max) during an IVR procedure . As. Asa,r v Model 1 b, natura Model 2 c.skin,max,Ka to establish a method that would bring the value of Dskin,max,Ka estimated indirectly from the Total Ka,r value closer to the more directly estimated Dskin,max,RPLGD value, we first analyzed the factors giving rise to variation in the Dskin,max,RPLGD/Total Ka,r ratio and then devised a new method for correcting for this variation. Finally, we validated the efficacy of this new correction method using a separately prepared validation data set. Our objective was to improve the accuracy with which the Dskin,max for patients undergoing NIR can be estimated from the Total Ka,r to help prevent skin damage by providing the operator with real-time Dskin,max measurements during NIR procedures. This method may provide a new means of utilizing DICOM-RDSR data.In this study, to optimize the process for estimating DThe test data set comprised 50 patients who underwent cerebral angiography in our hospital between October 2015 and July 2016 , and the validation data set comprised 50 patients who underwent cerebral angiography in our hospital between August 2016 and September 2017 .Angiography was performed using a single-plane angiography system equipped with a flat-panel detector. The tube voltage and tube current were adjusted via auto exposure control, and scanning was conducted at a fluoroscopy pulse rate of 15 pulses/s and an exposure frame rate of 3 frames/s. A 1.5 mm Al + 0.6 mm Cu filter was automatically selected and applied during fluoroscopy, and a 1.0 mm Al filter was applied during exposure.skin,RPLGD) from the patient\u2019s head to their neck was measured using the RADIREC\u00ae system (x) :y = 0.00RPLGD from Equation (1) using the representative effective energies for fluoroscopy and the exposure obtained from the individual DICOM-RDSR data for the 50 patients in the test data set; then, we calculated the weighted calibration factor from the fluoroscopy Ka,r and the exposure Ka,r. We next defined the Total CFRPLGD,weighted as the mean CFRPLGD,weighted for all 50 patients and converted the RPLGD readout values to Dskin,RPLGD according to Equation (2) below below a:Dskin,Rskin,RPLGD values at the 64 dose monitoring points were Dskin,max,RPLGD.While using the RADIREC system, we assumed that the maximum value of all Dskin,max,RPLGD and Total Ka,r for the 50 patients in the test data set was defined as CFKa,constant, and Dskin,max,Ka was estimated using Equation (3) below below b:Dskin,mskin,max,RPLGD/Total Ka,r and the Total Ka,r, Fluoroscopy Ka,r, Exposure Ka,r, Fluoroscopy Time, Number of DSA, Number of Frames, and the Fluoroscopy Ka,r/Total Ka,r in the various combinations from the DICOM-RDSR data recorded for the 50 patients in the test data set. In light of the results, we used the Total Ka,r to Dskin,max,Ka conversion factor , an arbitrary function that minimizes the error between the estimated Dskin,max,Ka and the Dskin,max,RPLGD, to estimate the Dskin,max,Ka for each individual patient according to Equation (4) c:Dskin,mskin,max,Ka estimated indirectly using the two maximum skin dose estimation models above (Estimation Models 1 and 2) and the value of Dskin,max,RPLGD estimated directly from RPLGD readouts. We calculated the root mean squared error (RMSE), mean absolute error (MAE), and coefficient of determination (R2) between Dskin,max,Ka and Dskin,max,RPLGD, and compared the goodness of fit of the two estimation models.Using the 50 patient test data set, we carried out a regression analysis between the values of DRPLGD,weighted, we determined the Total CFRPLGD,weighted. We then compared the goodness of fit of the two maximum skin dose estimation models (Estimation Models 1 and 2) via the same method as that used for the test data set.Using the 50 patient validation data set, after first determining that there was little variation in CFt-test, with p < 0.05 regarded as indicating significance.SPSS was used for statistical analyses. Differences between the mean values of the test data set and the validation data set were tested for significance using Welch\u2019s This study was approved by the Ethics Committee of Shinkomonji Hospital .RPLGD,weighted, the RPLGD compensation factors weighted by the Ka,r for fluoroscopy, and the exposure obtained from the DICOM-RDSR data for the 50 patients in the test data set. CFRPLGD,weighted exhibited little variation at 0.272 \u00b1 0.004 , suggesting that, in practical terms, the effect of patient differences on CFRPLGD,weighted is negligible, so a value of 0.272 for Total CFRPLGD,weighted was adopted. The highest of the Dskin,RPLGD values at the 64 sites calculated for each patient was used as Dskin,max,RPLGD.skin,max,RPLGD/Total Ka,r for the 50 patients in the test data set was 0.575 \u00b1 0.075 , so a value of 0.575 for CFKa,constant was used to estimate Dskin,max,Ka using Equation (3).The Da,r, Fluoroscopy Ka,r, Exposure Ka,r, Fluoroscopy Time, Number of DSA, Number of Frames, or Fluoroscopy Ka,r/Total Ka,r and Dskin,max,RPLGD/Total Ka,r alone alone d, so Equskin,max,Ka was estimated using Equations (4) and (5).Dskin,max,Ka estimated using Estimation Models 1 and 2 and Dskin,max,RPLGD. We found that the correlation was high for both estimation methods but that Estimation Model 2, which used CFKa,function as the conversion factor for individual patients, exhibited a better goodness of fit than Estimation Model 1 in terms of RMSE, MAE, and R2, demonstrating the superiority of Estimation Model 2 , so a value of 0.562 was used for CFKa,constant. As in the test data set, linear regression did not show any significant correlation between Total Ka,r, Fluoroscopy Ka,r, Exposure Ka,r, Fluoroscopy Time, Number of DSA, Number of Frames, or Fluoroscopy Ka,r/Total Ka,r , or Dskin,max,RPLGD/Total Ka,r , so a vatal Ka,r . Howeverr ratio) d, so theskin,max,Ka estimated by Estimation Models 1 and 2 using these values and Dskin,max,RPLGD showed that although the correlations were high for both estimation methods , Estimation Model 2, which used CFKa,function as the conversion factor for individual patients, exhibited a better goodness of fit than Estimation Model 1 in terms of the RMSE, MAE, and R2, demonstrating the superiority of Estimation Model 2 for the imaging of six major patient groups for the three purposes of preoperative diagnostic angiography, postoperative diagnostic angiography, and endovascular treatment [skin,max in real time during NIR procedures, and informing the operator, as required, if this value approaches the threshold value [One method for reducing the stochastic effects of IVR is to use the diagnostic reference level (DRL) to keep the radiation dose administered to the patient \u201cas low as reasonably achievable (ALARA)\u201d while guaranteeing the image quality required for diagnostic imaging ,29,30. Creatment . Howeverld value .a,r is constantly displayed on the angiography system monitor during treatment procedures, and its recording in DICOM-RDSR is also obligatory [skin,max simply and in real time at every medical facility where NIR is performed. In NIR, however, because the direction of X-ray irradiation and the extent of irradiation are constantly changing, the accurate estimation of Dskin,max is not necessarily simple, and the discrepancy between the values of Total Ka,r and Dskin,max mean that each individual institution should use its own conversion coefficient.A wide range of data is acquired for DICOM-RDSR, including the tube current and voltage, scanning data (such as exposure time and number of exposures), distance from the X-ray focal point to the detector, open area of the irradiation aperture, entrance angle, area dose, and patient entrance reference point dose. Because these data are acquired automatically for each fluoroscopy and exposure event, they can be used to manage medical radiation exposure for patients undergoing IVR ,39,40,41ligatory , meaningskin,max,RPLGD using the RADIREC system and estimated Dskin,max,Ka intraoperatively in real time by multiplying the Total Ka,r by the mean Dskin,max,RPLGD/Total Ka,r ratio as CFKa,constant (Schema 1b). However, Total Ka,r is the sum of all the X-ray entrance angles, and as the X-ray entrance angles are completely different for each patient, the Dskin,max,Ka is often larger or smaller than the actual Dskin,max,RPLGD. Theoretically, if the X-ray entrance angle does not change at all during the procedure, the value of Dskin,max,RPLGD/Total Ka,r increases and approaches 1. Conversely, if the X-ray entrance angle varies widely, the ratio will be lower. However, to our best knowledge, no index that provides an appropriate indication of variation in the X-ray entrance angle has yet been reported, and ours is the first study to demonstrate that a quadratic equation for the Ka,r ratio can adequately explain the variation in the value of Dskin,max,RPLGD/Total Ka,r.We previously analyzed Dskin,max,RPLGD and indirectly estimated Dskin,max,Ka. Applying the CFKa,function to the Ka,r ratio quadratic equations (see Equation (5) for the test data set and Equation (6) for the validation data set) and estimating the individual Dskin,max,Ka for each patient revealed a strong corrective effect in the high-dose region of the validation data set and a weak corrective effect in the low-dose regions of the test data set and the validation data set , resulting in a low Ka,r ratio and increasing the Dskin,max,RPLGD/Total Ka,r (Ka,function value can also be applied for appropriate correction of Dskin,max,Ka. Applying CFKa,function weighted by the Ka,r ratio therefore facilitates more accurate estimation of Dskin,max,Ka.data set . This mancreases d, and aptal Ka,r d. As in Ka,function using the Fluoroscopy Ka,r and the Total Ka,r data recorded in the DICOM-RDSR, but as X-ray entrance angle data are also recorded for each fluoroscopy and exposure event, analysis of these data may also enable us to develop an index of the degree of variation in the X-ray entrance angle, potentially further increasing the accuracy of estimating Dskin,max,Ka. As DICOM-RDSR is currently obligatory for all angiography systems both in Japan and overseas, it is a tool that is readily available in most institutions. Further studies should be conducted to explore other potential uses of DICOM-RDSR to reduce patient radiation exposure.In this study, our objective was to construct a CFa,r/Total Ka,r for each patient by the Total Ka,r provides a more accurate estimate than multiplying with a constant conversion factor during cerebral angiography, including NIR procedures, in real time.In this study, it was suggested that multiplying a conversion factor using the quadratic function for the ratio of Fluoroscopy K"} +{"text": "In \u201cUndergraduate Medical Competencies in Digital Health and Curricular Module Development: Mixed Methods Study\u201d :e22161) the authors noted three errors.One author's name was displayed as:David BackIt has now been corrected to:David Alexander BackOne affiliation for David Alexander Back was listed as:Bundeswehr Hospital Berlin, Clinic for Traumatology and Orthopedics, Septic-Reconstructive Surgery, Berlin, GermanyIt has now been corrected to:Department of Traumatology and Orthopaedics, Septic and Reconstructive Surgery, Bundeswehr Hospital Berlin, Berlin, GermanyThe phone number for corresponding author was incorrectly listed. It has been changed to:49 30 2841 1240The correction will appear in the online version of the paper on the JMIR Publications website on December 7, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "It is found in many different tissues and body fluids including the liver, articular cartilage, saliva and plasma . LysozymProteomics represents a valuable tool for diagnosis and is complementary to immunohistochemistry and gene sequencing. The advantage of proteomics is the ability to directly characterise proteins in the amyloid deposits. In certain circumstances, this approach can be limited by the normal requirement to use trypsin as the proteolytic enzyme.(p.W82R) in which we highlight the importance of the combined use of trypsin and Asp-N to identify the amyloid composition. The W64R lysozyme mutation has been originally described by Valleix et\u00a0al. [Here, we report a case of a patient carrying the mutation W64R x et\u00a0al. in 2002.Supplementary Table 1) including lysozyme which was identified with high Mascot score (1403) and a protein coverage of 66%. Peptides containing the W64R mutation were not detected since the additional tryptic cleavage site generated by a W\u2192R change resulted in the generation of small fragments outside the normal range of the instrument. A miscleaved variant peptide 51\u201364, (R)STDYGIFQINSRYR, was observed, however, the confidence in the assignment was low ). The wild type 63\u201369 and the miscleaved 63-97 peptides were not detected (Supplementary Table 2).A sample of Congo red positive formalin-fixed paraffin-embedded (FFPE) GI tissue was collected by laser capture dissection and analysed by proteomics using trypsin as the digestion enzyme . Data wedetected . To detedetected . This isSupplementary Table 3). Lysozyme protein coverage was only 7% obtained by Asp-N digestion and this is much more limited compared to the coverage achieved by trypsin digestion. However, the peptide 53\u201366, DYGIFQINSRYRCN(D), containing the tryptophan to arginine amino acid substitution, was identified after Asp-N digestion ). There was no evidence for the wild type peptide (Proteomic analysis following Asp-N digestion was then performed to confirm this finding in a separate specimen of Congo red positive GI amyloid. Lysozyme was identified together with a number of other proteins ( peptide .In conclusion, we have confirmed the original observation that the wild type lysozyme cannot be detected in natural amyloid fibrils . This isFurther, we stress the importance of the combined use of trypsin and other enzymes such as Asp-N to specifically detect the variant peptide in the amyloid tissue.Wolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, UKP. Patrizia MangioneWolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, UKDepartment of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, ItalyGuglielmo Verona, Dorota Rowczenio, Julian D. Gillmore and Graham W. TaylorWolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, UKVittorio BellottiWolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, UKDepartment of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, ItalyDiana CanettiWolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, UKd.canetti@ucl.ac.ukAlexandra Moura, Paola Nocerino, Janet A. Gilbertson and Nigel B. Rendell"} +{"text": "The dataset deals with the air quality perceived by citizens before and during the enforcement of COVID-19 restrictions in ten countries around the world: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. An online survey conveniently translated into Chinese, English, Italian, Norwegian, Persian, Portuguese collected information regarding the perceived quality of air pollution according to a Likert scale. The questionnaire was distributed between 11-05-2020 and 31-05-2020 and 9 394 respondents took part. Both the survey and the dataset (stored in a Microsoft Excel Worksheet) are available in a public repository. The collected data offer the people's subjective perspectives related to the objective improvement in air quality occurred during the COVID-19 restrictions. Furthermore, the dataset can be used for research studies involving the reduction in air pollution as experienced, to a different extent, by populations of all the ten countries. Specification table\u2022The data are related to the perception of air quality and air pollution during the COVID-19 restrictions as experienced by a large pool comprising 9 394 respondents located in ten countries on six continents\u2022The data can be useful for researchers dealing with the environmental and tropospheric changes occurring during the COVID-19 restrictions\u2022The data can be used to assess the relationship between the perceived and the quantified change in air quality and air pollution during the COVID-19 restrictions\u2022The data can be of interest to both citizens and policymakers to realise the tremendous lesson learned during COVID-19, being air quality a key indicator for sustainable developmentValue of the data1The dataset provides information regarding the quantity of air pollution perceived before and during the restrictions enforced in ten countries around the world as a consequence of the COVID-19 pandemic: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States . The dataset is stored in a public repository as Microsoft Excel Worksheet 2The online survey has assessed the air quality as subjectively perceived by citizens in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. The online questionnaire was hosted on two platforms: Google Forms and WenJuanXing (Chinese version) and promoted on professional and social networks. The survey content was the same for each language; only the question regarding the respondents\u2019 geographical location was tailored for each country. A Likert scale was employed to collect information about subjective perceptions All the survey respondents informed their consent before joining the survey consistent with the Declaration of Helsinki.Diego Maria BarbieriConceptualization, Methodology, Formal analysis, Investigation, Resources, Data curation, Writing - Original Draft, Visualization, Project administrationBaowen LouConceptualization, Methodology, Formal analysis, Investigation, Resources, Data curation, Writing - Original Draft, VisualizationMarco PassavantiConceptualization, Methodology, Investigation, Writing - Original Draft, VisualizationCang HuiInvestigation, Data curation, Writing - Review & Editing, Visualization, SupervisionDaniela Antunes LessaInvestigation, Data curationBrij MaharajInvestigation, Data curationArunabha BanerjeeInvestigation, Data curationFusong WangInvestigation, Data curationKevin ChangInvestigation, Data curationBhaven NaikInvestigation, Data curationLei YuInvestigation, Data curationZhuangzhuang LiuInvestigation, Data curationGaurav SikkaInvestigation, Data curationAndrew TuckerInvestigation, Data curationAli Foroutan MirhosseiniInvestigation, Data curationSahra NaseriInvestigation, Data curationYaning QiaoInvestigation, Data curationAkshay GuptaInvestigation, Data curationMontasir AbbasInvestigation, Data curationKevin FangInvestigation, Data curationNavid GhasemiInvestigation, Data curationPrince PeprahInvestigation, Data curationShubham GoswamiInvestigation, Data curationAmir HessamiInvestigation, Data curationNithin AgarwalInvestigation, Data curationLouisa LamInvestigation, Data curationSolomon AdomakoInvestigation, Data curationThis research has not received any specific grant from funding agencies in the public, commercial, or not-for-profit sectors."} +{"text": "Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other substances, both licit and illicit, including new psychoactive substances (NPS). Among them, the misuse of prescription drugs involves not only traditionally recorded substances, such as benzodiazepines and opioid pain relievers, but also gabapentinoids ; some antidepressants, e.g., bupropion and venlafaxine; some second-generation antipsychotics, e.g., quetiapine and olanzapine. Moreover, the use of some OTC for recreational purposes appears on the increase, especially in vulnerable categories such as young people/youths, including the use of high dosages of the antidiarrheal loperamide; first-generation antihistamines, e.g., promethazine, cyclizine, and diphenhydramine; cough and cold preparations containing dextromethorphan and/or codeine. In this context, the role of the Internet has rapidly increased, playing a significant role both in the diffusion of emerging trends of drug misuse among users and experimenters, and the marketing, sale, and distribution of drugs through online pharmacies. This phenomenon within the context of a rapidly modifying drug scenario is a globally recognized health problem, determining severe adverse consequences, including fatalities, and represents a challenge for clinicians in general, psychiatrists, public health, and drug-control policies. Over the last twenty years or so, both the emerging use of new psychoactive substances (NPS) and the misuse of medications that are not already controlled are rapidly becoming a worldwide health concern ,2,3,4. WIn this context, the role of the Internet in changing drug misuse scenarios is central, since playing a significant role in the marketing, sale, and distribution of a range of psychoactive, including prescription, drugs ,20,21. IThis ever-changing drug scenario represents a challenge for accident and emergency units; healthcare services ; public"} +{"text": "Andr\u00e1s G\u00e9zsi. In addition to affiliation 1, he is also affiliated to:In the published article, there was an error concerning affiliation of MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Semmelweis University, Budapest, HungaryDepartment of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, HungaryThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Vingselina genus group, including genera Anaselina Storozhenko, 2019, Paraselina Storozhenko, 2019, Selivinga Storozhenko, 2019 and Vingselina Sj\u00f6stedt, 1921. The systematic position of this group, currently assigned to Batrachideinae (Bufonidini), is probably not correct. In this study new records are presented of Anaselinaminor , Paraselinabrunneri , P.trituberculata , and Selivingatribulata Storozhenko, 2019, all except A.minor the first records of the species since their original descriptions. The first photographs of living specimens of A.minor, P.brunneri, P.trituberculata and S.tribulata are provided and their habitats described. All the records were compiled by citizen scientists who use online social media, such as iNaturalist. Lastly, P.multifora syn. nov. represents a junior synonym of P.brunneri.Knowledge on the pygmy grasshoppers of Australia is, despite the numerous endemics being described from this unique continent, still scarce. Of interest is the Monotremata), numerous marsupials , emus (Dromaiusnovaehollandiae), lyrebirds , or the Wollemi pine (Wollemianobilis) found on bark, and among the rarest grasshoppers on the planet from the point of view of the numbers of records , 2) Vingselinacrassa Sj\u00f6stedt, 1921, 3) Anaselinaminor , 4) P.trituberculata , 5) P.multifora , 6) Selivingatribulata Storozhenko, 2019 belong to Bufonidini, together with Bufonides (New Guinea), Hyperyboella , and Vilma (Solomon Islands) .Taxonomy follows We follow the morphological terminology presented by Batrachideinae: Bufonidini, and those specimens are the only published specimens of said species. The exception are a few non-type specimens of Anaselinaminor, originating from Cape Tribulation, deposited in the Zoological Institute of the Russian Academy of Sciences (ZIN) and depicted by Batrachideinae have been deposited:We have examined type specimens of all the Australian MCZ US Museum of Comparative Zoology of Harvard University in Cambridge, Massachusetts, USA ;NHMWNaturhistorisches Museum Wien, Wien, Austria ;NHRSNaturhistoriska riksmuseet, Stockholm, Sweden ;QMQueensland Museum, Queensland, Brisbane, Australia ;ZIN Zoological Institute of the Russian Academy of Sciences, St. Petersburg, Russia .A.minor in one and S.tribulata in two additional localities , Tiny helmed groundhopper1. Vingselinaminor one century ago , Angled Australian barkhopper2. Paraselinabrunneri based on a female holotype and three female paratypes, from Dorrigo (Macleay Range) and Salisbury, did not see Bol\u00edvar\u2019s type, but only P.brunneri , and 3) the size of hind femora .There is considerable infraspecific variability in size, coloration, and angulation of the median carina of the pronotum. Differences separating The types of the two taxa are very similar, but in addition we have new records, which provide evidence of this infraspecific variability, especially in the size and morphology of the median carina of the pronotum.Paraselinatrituberculata , Triple-bump Australian barkhopper3. Paraselinatrituberculata that bears three smaller warts on the median carina adults have been observed every month of the year.The species inhabits the northern part of Queensland and is, for now, known from Cape Tribulation , Kuranda Figure , Tully GEven though the species has been described only recently, DR had already been aware of its existence since 2000, and there is indeed a notable population in the author\u2019s garden (pers. comm. H. Devriese).Even though throughout the study we call them hould be . Bufonidsegments , a typicnce 1887 , are in Anaselina, Paraselina, and Selivinga inhabit humid forests of eastern Australia and are easily distinguishable from each other. In the past it was difficult to study material from different places rapidly. In this study, we show that mainly with records from online social media platforms we can add knowledge to the biology and taxonomy of certain species. Today, it is much easier to study material from all over the world and communicate with experts and citizen scientists. Citizen science records contributed to the knowledge of morphology of Paraselinabrunneri and P.multifora, which had not been recorded for many decades. From these photos, we have found that specimens vary in certain morphological traits and that micro-differences used to separate P.brunneri from P.multifora are not species-specific, so P.multifora should be considered a synonym of P.brunneri.Poor taxonomic knowledge does not prevent us from assessing distributions of Australian barkhoppers, nor from separating species. Species of the genera Anaselinaminor is the smallest member of the Vingselina genus group, now known from three localities in the northern Queensland. Selivingatribulata was described only last year from Cape Tribulation and here we report three new localities for this species, with a description and depiction of its habitat. We also present the very first record of Paraselinatrituberculata since its description, and confirm that the species is only overlooked, not extinct. Social media platforms are already used by scientists, and studies which will make it available for people to record and learn about species in a more visual and simple manner, are strongly needed.A.minor, P.brunneri, P.trituberculata, and S.tribulata are easily identifiable, but rare species. Most of the knowledge on their biology was hitherto based on old museum specimens. Here, with united forces of citizens, who post photos online, and experts, who use online social platforms in order to identify specimens, we present an annotated distribution map of the aforementioned species, as well as a taxonomic scrutiny on the system of their classification. Citizen science is not age-limited nor profession-limited. In 2020, anybody and everybody can contribute to biodiversity studies. Evidence is presented by the authors of this study, among which there are an 11-year-old boy and a retired English teacher.In conclusion,"} +{"text": "Professor Todd B. Marder grew up in Brooklyn, New York, and received his BSc from the Massachusetts Institute of Technology, Cambridge , and his PhD from the University of California at Los Angeles . This was followed by postdoctoral research at the University of Bristol . Working with the well-renowned inorganic chemists Professor Alan Davison, FRS (BSc), Professor Fred Hawthorne (PhD), and Professor Gordon Stone, CBE, FRS (postdoc) embedded the seeds of curiosity in inorganic chemistry in him, and it initiated his passion for organometallic and boron chemistry, homogeneous catalysis, dynamic NMR studies, and MO calculations. After two years as a visiting research scientist at DuPont Central Research, Wilmington, Delaware (USA), he began his independent academic career at the University of Waterloo (Canada) in 1985, where I first encountered this young, highly enthusiastic, gentleman inorganic chemist. I am proud to be the first PhD student to have graduated from his group.Within a short span of about 8 years, he was promoted first to Associate Professor and then Full Professor in 1993. Diversity in chemistry was apparent in Todd\u2019s very first collection of young graduate students: indenyl-rhodium chemistry (Ashok Kakkar); Rh and Pt-acetylide chemistry: Pauline Chow, Davit Zargarian , M.J. Gerald Lesley , Dr. Graham Stringer and Dr. Ian R. Jobe ; metal boryl complexes and metal-catalyzed hydroboration chemistry: Steve Westcott . As they say, there is always a woman behind every successful man, and Todd met his wife and a gem of a person, Anne, who was also teaching at the University of Waterloo. These two are a team that continue to support some of the best scientists in their care. In fact, their son, Ian, is an Assistant Professor in Criminology in the Department of Law at Maynooth University, Ireland, so academics run in the family.With the excellence in chemistry that Todd demanded from himself and his crew, awards started to follow, the first being the Rutherford Memorial Medal for Chemistry (1995), given by the Royal Society of Canada to the leading chemist in Canada under 40 years of age.After spending 12 years in Canada, Todd was lured by the British way of life, and decided to move from the colonies to the kingdom in 1997, when he accepted the Chair in Inorganic Chemistry at the University of Durham in England. He received the Royal Society of Chemistry Award in Main Group Element Chemistry in 2008 for his contributions to the chemistry of boron and its organometallic compounds and their applications, and a Japan Society for the Promotion of Science (JSPS) Invitation Fellowship (Japan), a Humboldt (Senior) Research Award (Germany), and the Royal Society (UK) Wolfson Research Merit Award, all in 2010. It was finally the lure of German beer, sausages and boron chemistry that brought him to the Institut f\u00fcr Anorganische Chemie, Julius-Maximilians-Universit\u00e4t W\u00fcrzburg (Germany) in 2012, as Professor and Chair I of Inorganic Chemistry, as well as co-Head of the Institute for Sustainable Chemistry & Catalysis with Boron. Todd also won the Royal Society of Chemistry Organometallic Chemistry Award and was elected to the Bayerische Akademie der Wissenschaften (Bavarian Academy of Sciences) in 2015, Fellow of the American Association for the Advancement of Science (AAAS) in 2018, and Fellow of the European Academy of Sciences (EurASc) in 2019. In 2018, he was also awarded Docteur Honoris Causa, by the Universit\u00e9 de Rennes 1, France.Todd loves varied cultures, food, and his many friends scattered around the world and, prior to the current pandemic, would never miss an opportunity to travel both to contribute and to learn. This has led to several Visiting and similar Professorships in Europe , Asia , and Australia . He has served on the editorial board of several journals including Inorganic Chemistry, Organometallics, the Journal of Organometallic Chemistry, Applied Organometallic Chemistry, Canadian Journal of Chemistry, Crystal Engineering, and Chinese Journal of Chemistry.Todd has given over 400 invited lectures worldwide, published over 385 papers with an h-index of 88 and around 25,000 citations (WoS). The co-workers he has trained occupy academic (over 35 of them) as well as industrial and other positions all over the world, and their success is his proudest achievement. Indeed, he refers to us as his children, and our academic offspring as his grandchildren, and has even had the pleasure of supervising a postdoc who was also his academic great granddaughter, Marie-H\u00e9l\u00e8ne Thibault !2neop2, is now available commercially world-wide and is produced in multi-ton quantities. He also works in the fields of conjugated organometallic [Todd embraces diversity not only in his group members and numerous local and international collaborators, but also in his research interests ,18,19,20metallic , organobmetallic ,14,15,16metallic ,18,19 foMolecules: \u201cBoron in Catalysis and Materials Chemistry: A Themed Issue in Honor of Professor Todd B. Marder on the Occasion of His 65th Birthday\u201d. It includes excellent review articles on conjugated N^C-organoboron materials, and tri(boryl)-alkanes and -alkenes as versatile reagents in organic synthesis [Boron chemistry continues to offer a diverse platform for new directions in catalysts ,22,23, aynthesis ,32, and ynthesis ,37,38,39"} +{"text": "Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients\u2019 nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR model. The TEP identified micronutrients from the \u201cEuropean Union (EU) Register of nutrition and health claims made on foods\u201d that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH terms and adding to each of them the words \u201cdental implants\u201d and \u201cosseointegration\u201d. The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the \u201cEU Register on nutrition and health claims\u201d for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation. Osseointegration is defined as \u201ca process whereby a clinically asymptomatic rigid fixation of alloplastic materials is achieved and maintained in bone during functional loading\u201d . OsseoinIn addition to key factors that affect the osseointegration, such as the surgical technique, bone quality and quantity, postoperative inflammation or infection, smoking habits, and implant material and surface ,4,5,6,7,Several micronutrients affecting bone metabolism were demonstrated to have an influence on skeletal system; in particular, calcium, fluorides, magnesium, potassium, vitamin B6, vitamin D, and zinc positively influence bone health, reducing the risk of fracture . In addiRecent evidence demonstrated that some nutritional regimens directly influence alveolar bone parameters in experimental models of periodontitis ,12,13, oBone tissue repair mechanisms and bone metabolism are strongly influenced by nutritional aspects and are crucial to obtaining proper bone restoration optimizing osseointegration processes.The aim of this scoping review is to summarize the state of the art regarding the role of micronutrients, currently available in nutraceuticals or dietary supplements, on dental implantology, highlighting which of them, supported by evidence-based medicine (EBM), might effectively have an influence on the achievement and the maintenance of osseointegration after implant insertion surgery.In performing this scoping review, we followed the PRISMA-ScR model .As a first step, a technical expert panel (TEP) consisting of 11 medical specialists was established. In particular, the TEP was composed of two oral surgeons with expertise in osseointegrated dental implants, two periodontists with expertise in peri-implant oral tissues physiology and pathology, three bone specialists, two experts on scoping review methodology, one nutritionist, and one orthopedic surgeon.The TEP selected micronutrients from the \u201cEuropean Union (EU) Register of nutrition and health claims made on foods\u201d that have a relationship with bone and tooth health, included in dietary supplements and nutraceuticals. Therefore, the TEP planned a research on PubMed , selecting micronutrients as MeSH terms; to each of them, the following terms were added to run the PubMed Search Builder: \u201cdental implants\u201d, \u201cosseointegration\u201d. For example: (\u201cVitamin D\u201d [Mesh]) AND \u201cDental Implants\u201d [Mesh]) see .According to the objective of the study, the TEP defined the characteristics of the sources of evidence, considering for eligibility any researches published in medical literature in the last 10 years (last update on 16 October 2019), including only those in the English language.All types of studies were included in our scoping review, both pre-clinical and clinical studies. Methodological quality assessment was made according to the EBM pyramid: meta-analysis, systematic review, randomized controlled trial (RCT), cohort study, case\u2013control study, case series, and case report.Finally, the TEP summarized the resulting micronutrients with effective and safe daily doses that improve bone and tooth health.From the micronutrients listed in the \u201cEU Register of nutrition and health claims made on foods\u201d, the TEP selected the following 18 nutraceuticals that may have influence on bone and teeth: calcium, fluorides, magnesium, potassium, resveratrol, vitamin C (ascorbic acid), vitamin D, vitamin E , vitamin K2 , zinc, vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacinamide), vitamin B5 (pantothenic acid), vitamin B6, vitamin B7 (biotin), and vitamin B12 . HoweverIn particular, we included 11 studies concerning vitamin D, of which five were clinical studies , and six were preclinical studies on animals: two preclinical studies on animals concerning magnesium, two preclinical studies on animals for resveratrol, one preclinical study on animals concerning the supplementation with a combination of calcium, magnesium, zinc and vitamin D, two preclinical studies on animals concerning synthetic bone mineral , and one clinical study concerning vitamin C supplementation , Table 2In our scoping review, we included six preclinical studies on animal models, more precisely, on rats.Liu et al., in 2014 , found tZhou et al., in 2012 , demonstWu et al., in 2012 , inserteAkhavan et al., in 2012 , evaluatDvorak et al., in 2012 , showed Kelly et al., in 2008 , found tThe clinical studies on vitamin D that we included in this scoping review were three retrospective studies, one case series, and one case report.From the retrospective studies of Mangano et al. of 2016 and 2018In the retrospective study of Wagner et al. of 2017 , osteopoFretwurst et al., in 2016 , reporteAlso, Bryce and Macbeth, in 2014 , reporteWe included two animal studies that evaluated the effects of magnesium deficiency on osseointegration of titanium implants. The deficiency of magnesium led to lower cortical bone thickness, lower values of removal torque of the implants, and lower bone mineral density (BMD) ,41. In dDel Barrio et al., in 2010 , reporteWe found two animal studies that evaluated the effects of resveratrol intake on the osseointegration of titanium implants.In 2018, Ribeiro et al. demonstrPimentel et al., in 2016 , evaluatTakahashi et al., in 2016 , evaluatAlso, Watanabe et al., in 2015 , evaluatLi et al., in 2018 , evaluatTo the best of our knowledge, this is the first scoping review to investigate the putative role of dietary supplements in affecting bone structural and mechanical properties involved in dental implant osseointegration, as well as in improving clinical outcomes, such as the maintenance of peri-implant tissue health and implant success rate.The Federal Food, Drug, and Cosmetic Act defines a dietary supplement as a product that is intended to supplement the diet, which bears or contains one or more ingredients including a vitamin, mineral, herb, and amino acid, or a concentrate, metabolite, constituent, extract, or combinations of these . The terIt should be stressed, however, that there is no consensus with regard to \u201cnutraceutical\u201d definition or similar terms. Aronson recently considered that the term \u201cnutraceuticals\u201d is too vague and should be abandoned, even if he did not propose any robust alternatives .According to the recent data of the United States (US) Centers for Disease Control and Prevention\u2019s National Health and Nutrition Examination Survey (NHANES), more than 25% of the US population had an insufficient intake of vitamins A, C, D, and E, as well as calcium, magnesium, and potassium in their diet; thus, the modern diet of Western countries does not seem to have an adequate intake of micronutrients. It was reported that micronutrient deficiencies affect around two billion people worldwide . HoweverSeveral micronutrients are hypothesized to have an influence on skeletal system, particularly on jaw bone and alveolar bone and on dMoreover, Wagner et al. showed tVitamin D deficiency commonly occurs in the general population. This hormone has a crucial function in skeletal mineralization, but also plays an important role in immunity and inflammatory response, increasing anti-inflammatory cytokines and decreasing pro-inflammatory ones .Bashutski et al. showed tAlso, vitamin C deficiency may have a role in tissue healing and stability around dental implants. This micronutrient plays an important role in the biosynthesis of collagen, which is an important component of connective tissue of the gingiva, peri-implant mucosa, and alveolar bone . These eBMP-2 (p = 0.011), BMP-7 (p = 0.049), and OPN (p = 0.002) genes in the resveratrol-fed group than in the control group.With regard to resveratrol, Casarin et al. investigRibeiro et al. reportedHowever, considering the results of our research, several micronutrients are non-authorized or even not considered by the \u201cEU Register on nutrition and health claims\u201d on the basis of current scientific evidence.Major nutrients involved in skeletal health include calcium, phosphorus, vitamin D, magnesium, and potassium, but other micronutrients and trace elements such as boron, selenium, iron, zinc, and copper also impact bone metabolism. Information on the influence of such \u201cminor\u201d elements coming from studies on nutrient depletion and studies on osseointegration is still lacking.Our scoping review overall demonstrated a lack of data about the effects of micronutrients and nutraceuticals on osseointegration of dental implants, although, for some of them, such as vitamin D, there was a clear association among their deficit, reduced osseointegration, and increased early implant failure incidence in both animal and human studies.Some micronutrient deficiencies are supposed to increase oxidative stress and inflammation and to affect collagen structure and bone mineralization. For these reasons, it would be desirable that further studies investigate the hypothesis of an influence of micronutrients and nutraceuticals on dental implant osseointegration and long-term success, as well as the opportunity of a diet integration to enhance peri-implant wound healing, bone healing, and peri-implant tissue stability. However, data for many micronutrients that might modulate bone metabolism are lacking, and dosing regimens for dietary supplements that improve dental implant osseointegration are not defined according to available findings; furthermore, safety issues remain to be carefully investigated. In conclusion, our findings support an ancillary role of vitamin D, in patients with vitamin D deficiency, as well as vitamin C supplementation, in facilitating the success of the dental implant surgery."} +{"text": "Materials chemistry has been one of the most talked-about areas of materials research over the past decades. Spanning from polymers and composites to metallic, ceramic, and hybrid materials, as well as nano- and micromaterials, chemistry is unique in creating diverse arrays of new materials for applications in catalysis, energy conversion and storage, advanced electronics, environmental devices, drug delivery, smart textiles, packaging systems, or scaffolding for tissue engineering\u2014to name but a few, with potential broad scientific and societal impact.At the same time, matching materials and sustainability is becoming crucial, as a result of ever more stringent regulatory requirements in the European Union, North America and developed Asian countries ,2,3,4. TSpecial importance is being attributed to the efficient use of the starting materials for obtaining the desired functional final products, while avoiding waste and the use of toxic substances, minimising the need for energy and using renewable resources ,8,9,10. Molecules, is reported in the Reference section of this Editorial [A selection of cutting-edge \u201cHot Papers\u201d in the field of renewable materials, published in the Materials Chemistry Sector of ditorial ,23,24,25Molecules is to provide an open-access publishing platform for the effective dissemination of high-quality scientific outputs at the core of research on Materials Chemistry. The Section invites papers related to either experimental or theoretical studies about synthesis, properties, characterization, and application of materials in the widest sense .The target of the \u201cMaterials Chemistry\u201d Section in Molecules? Discoverability, to begin with. Open access, indeed, translates into wider readership, greater visibility and increased citations; moreover, the Editorial Team of Molecules ensures online dissemination through social media tools, to maximize the visibility of the published research. Next, the Journal is associated with a favorable and constantly increasing impact factor (3.267). Furthermore, the committment of the Journal to the peer-review process ensures the high quality of the article accepted and a very efficient timeline.What are the benefits of publishing in the \u201cMaterials Chemistry\u201d Section of Molecules. Please also note that, in doing this, the \u201cMaterials Chemistry\u201d Section should be selected from the drop-down menu.Materials Chemistry is experiencing a paradigm shift from traditional production technologies and practices to one that assigns value to the replacement of fossil fuels with renewable resources, waste minimization, and avoiding the use of substances that pose serious risk to human health and the environment. In this context, the prospect for research on alternative feedstocks, environmentally benign reagents, solvents, and catalysts, and safer and more readily recyclable products, as well as non-persistent, non-bioaccumulative, eco-compatible materials, looks exciting. We hope you will consider submitting your materials\u2019 chemistry-related manuscripts to"} +{"text": "China\u201d . Secondly, the email of the corresponding author should have been presented as \u201cjhzhong28@163.com\u201d (instead of as \u201cjizhong28@163.com\u201d). Therefore, the authors\u2019 names and affiliations in this paper should have been presented as follows (changes are highlighted in bold):After the publication of the above paper, the authors have realized that the address presented for the authors, and the email address for the corresponding author, were both published containing errors. First, the address affiliation should have been presented as \u201cDepartment of Hematology, Renji Hospital, GUOQIANG ZHANG, JIHUA ZHONG, TING WANG and LU ZHONGSchool of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. ChinaDepartment of Hematology, Renji Hospital, Correspondence to: Professor Jihua Zhong, Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong New Area, Shanghai 200127, P.R. ChinaE-mail: jhzhong28@163.comThe authors regret that these errors with the author affiliations and the corresponding author\u2019s email address were not noticed prior to the publication of their paper, and apologize for any inconvenience caused."} +{"text": "In the published article, there was an error regarding the affiliations for Peng Shen. Instead of the affiliation \u201cDepartment of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China\u201d, they should have the affiliation \u201cDepartment of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The Nutrients Editorial Office would like to update the error in the original published version .2,4,*,\u2020\u201d, has been changed to \u201cMaria Izquierdo-Pulido 1,2,4,*,\u2020, who also belongs to the Department of Nutrition, Food Science and Gastronomy, School of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.\u201d The affiliation of the fifth author, \u201cMaria Izquierdo-Pulido We would like to apologize for any inconvenience caused to the authors and readers by this mistake. We will update the article, and the original version will remain available on the article webpage."} +{"text": "Correction to:Scientific Reports 10.1038/s41598-018-35670-3, published online 13 February 2019In the original version of this Article, C\u00edntia Martins was incorrectly listed as a second corresponding author. The correct and only corresponding author for this Article is Ellie Bergstrom. Correspondence and request for materials should be addressed to ellie.bergstrom@griffithuni.edu.au.Further to this, the original version of this Article omitted an affiliation for Ellie Bergstrom. The correct affiliations for Ellie Bergstrom are listed below:School of Environment & Science and Australian Rivers Institute \u2013 Nathan Campus, Griffith University, 170 Kessels Road, Brisbane, Nathan, Queensland, 4111, AustraliaLaboratory of Phycology, Department of Botany, Center for Biological Sciences, Federal University of Santa Catarina, 88040-970 Florian\u00f3polis, SC, BrazilThese errors have now been corrected in the HTML and PDF versions of the Article, and in the accompanying Supplemental Material."} +{"text": "There are errors in the Funding statement. The correct Funding statement is as follows: This work was supported by the Researchers supporting Project (RSP-2020/189) King Saud University, Riyadh, Saudi Arabia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.There is an error in affiliation 4 for author Giancarlo Polizzi. The correct affiliation 4 is: Dipartimento di Agricoltura, Alimentazione e Ambiente, Sezione di Patologiavegetale, University of Catania, Italy."} +{"text": "Scientific Reports 10.1038/s41598-020-72589-0, published online 27 May 2020Correction to: The Acknowledgements section in this Article is incomplete.Tara Pacific consortium, France Genomique Grant Number ANR-10-INBS-09, and the Genoscope/CEA. We are keen to thank the commitment of the people and the following institutions and sponsors who made this singular expedition possible: CNRS, CSM, PSL, KAUST, Genoscope/CEA, ANR-CORALGENE, agn\u00e8s b., the Veolia Environment Foundation, Region Bretagne, Serge Ferrari, Billerudkorsnas, AmerisourceBergen Company, Lorient Agglom\u00e9ration, Oceans by Disney, the Prince Albert II de Monaco Foundation, L\u2032Oreal, Biotherm, France Collectivites, Kankyo Station, Fonds Francais pour l\u2032Environnement Mondial (FFEM), Etienne Bourgois, UNESCO-IOC, the Tara Foundation teams and crew. Tara Pacific would not exist without the continuous support of the participating institutes. This publication is number 5 of the Tara Pacific Consortium.\u201d\u201cThis project has been funded through the should read:Tara Pacific consortium, France Genomique Grant Number ANR-10-INBS-09, and the Genoscope/CEA. We are keen to thank the commitment of the people and the following institutions and sponsors who made this singular expedition possible: CNRS, CSM, PSL, KAUST, Genoscope/CEA, ANR-CORALGENE, agn\u00e8s b., the Veolia Environment Foundation, Region Bretagne, Serge Ferrari, Billerudkorsnas, AmerisourceBergen Company, Lorient Agglom\u00e9ration, Oceans by Disney, the Prince Albert II de Monaco Foundation, L\u2032Oreal, Biotherm, France Collectivites, Kankyo Station, Fonds Francais pour l\u2032Environnement Mondial (FFEM), Etienne Bourgois, UNESCO-IOC, the Tara Foundation teams and crew. Tara Pacific would not exist without the continuous support of the participating institutes. We also thank Professor Russel Clark Perembo,\u00a0Alfred Yohang Ko\u2019ou, Augustine Mungkaje and Professor Simon Saulei, researchers of the Marine Scientific Research Committee and the National Research Institute of Papua New Guinea for the authorization of coral sampling and their valuable assistance during Tara expedition in Papua New Guinea. This publication is number 5 of the Tara Pacific Consortium.\u201d\u201cThis project has been funded through the Additionally, the information about research permissions is not included in the Article. The sampling and research described in this paper was approved by the Marine Scientific Research committee and the department of foreign affairs and trade of the independent state of Papua New Guinea, under the diplomatic clearance number 0232."} +{"text": "Nabiximols interact with both CB1 and CB2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before . We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad \u201cSpasticity-Plus Syndrome\u201d that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS.Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms . Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB In the last two decades, the availability of new disease-modifying therapies has radically changed the management of multiple sclerosis (MS) and relapsing\u2013remitting MS in particular , resultiA wide range of treatments are available to manage each of the MS symptoms \u20137. GivenMS pathology affects multiple areas of the central nervous system (CNS), producing therefore a multiplicity of symptoms that can be basically classified as sensory alterations, fatigue, importantly cognitive dysfunction, pain , visual and brainstem symptoms , those relating to mobility , psychologic/psychiatric alterations , bowel, sexual and bladder dysfunctions, sleep disorders, and paroxysmal symptoms . All these symptoms vary along the course of the disease, being more prevalent as the disease evolves 9\u201312) to total (4%) . Similar1% to totAtaxia, reported in up to 80% of MS patients at some point in their disease , and treBladder symptoms have been reported in approximately three-quarters of patients with MS , while sFatigue, depression, and cognitive impairment are also highly prevalent among patients with MS and impact quality of life even after accounting for physical disability , 27. CenIn summary, symptoms of MS are widespread, varied, often interlinked, and highly prevalent among patients with the disease. The impact on quality of life is substantial, and mobility is a concern for patients , 17. MS As detailed above, the symptoms of MS are varied and substantially impact patients' well-being. Management of symptoms is, however, a complex task requiring a multidisciplinary approach. In some cases, non-pharmacological interventions may be beneficial, e.g., physiotherapy for spasticity, but might have a limited time effect and the evidence supporting such approaches is not always strong , and phaAny pharmacological intervention has a risk of side effects and thisA syndrome in medicine is classically defined as a combination of signs and/or symptoms that forms a distinct clinical picture indicative of a particular disease or disorder . UsuallyAlthough the specific mechanisms of the above symptoms might vary, damage to the CNS is common to all of them and we could consider, for practical reasons, as forming part of a syndrome, in which we would denote this new broad \u201cSpasticity-Plus Syndrome\u201d as a useful concept to be used in the symptomatic management in MS. This could be considered as an extension of the definition of symptom clusters or complexes, which underscores two primary features that have been defined as the existence of \u201cthree or more symptoms that are related to each other and that the symptoms must be inter-related through a common etiology or statistically as a cluster or latent variable. Such concurrent symptoms likely have a synergistic influence on behavioral, functional, and QOL outcomes and co-occurring symptoms seemingly provide a more efficient target for management than a single, isolated symptom taken out of its clinical context\u201d .The framing of MS symptoms within a syndrome also implies that a single intervention, in this case one that targets the cannabinoid system, a widely distributed molecular system in the CNS, may potentially influence a range of different symptoms. The presence in MS patients of one or more of the symptoms contained in the broad \u201cSpasticity-Plus Syndrome\u201d concept (spasticity and/or spasms-cramps and/or pain and/or bladder dysfunction and/or sleep disorders and/or fatigue and/or tremor) would have to trigger in physicians the search of the other symptoms' presence and severity and the attempt to manage them as appropriately as possible with proven, well-tolerated, and as simple as possible to use options.1 and CB2, along with their ligands, the endocannabinoids, which are derived from fatty acids \u201347.CAnnabinoids for treatment of spasticity and other symptoms related toMultipleSclerosis study (\u201cCAMS\u201d) found si(\u201cCAMS\u201d) , 51. In (\u201cCAMS\u201d) . There i(\u201cCAMS\u201d) . MoreoveAs a clear limitation, we consider this as a preliminary conceptual proposal that has to be sustained in the future with new studies, not yet available, and that could give more background and support to our concept, so that the hypothesis would be testable and be a promising area of research in the field of symptomatic therapy. Another limitation is the fact that we do not know whether this concept could be applied to the spasticity present in other diseases such as spinal cord injury, stroke, etc., as it has not been surveyed yet as far as we know.1 and CB2 receptors.The numerous and varied symptoms associated with MS requires complex management with multiple drugs, all with potential side effects that may exacerbate other symptoms and with potential drug\u2013drug interactions. Recognition that a good number of MS symptoms might have a common or close underlying pathophysiology, or respond to a single therapy, in the form of a new broad \u201cSpastic-Plus Syndrome\u201d in MS may help simplify treatment of these symptoms with agents such as cannabinoids that target CB\u00d3F, LC-F, MM-G, PM, JP, and LR contributed conception and design of the study. \u00d3F wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.\u00d3F has received honoraria as consultant in advisory boards, as chair/lecturer in meetings, from participation in clinical trials and other research projects promoted by Actelion, Allergan, Almirall, Bayer-Schering, Biogen, Merck Serono, Novartis, Sanofi Genzyme, Roche, Teva, Orizon, and Araclon, and research support from the Hospital Foundation FIMABIS. LC-F has received compensation for consulting services and speaking fees from Merck, Novartis, Biogen, Bayer, Sanofi, Genzyme, TEVA, Almirall, Biopas, Ipsen, Celgene, and Mylan. MM-G has received compensation for consulting services and speaking fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, Roche, and Teva. PM has received compensation for consulting services and speaking fees from Almirall. JP has done consultancy work for Bayer HealthCare, Biogen, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Merck, and Almirall; has given lectures in congresses and symposia organized by Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva Pharmaceuticals; and has received funding for research projects from Almirall, Biogen, Novartis, and Sanofi-Genzyme. LR has received compensation for consulting services and speaking fees from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, TEVA, Almirall, and Mylan."} +{"text": "Our linear mixed-effects models required that for each individual the slope of the line of [18F]FDG data in the outcome and the slope of the peripheral blood transcript expression data correlate, i.e., the slopes of the outcome and explanatory variables had to be similar. Of 10,295 genes that changed as a function of time, we identified 639 genes whose expression profiles correlated with decreasing [18F]FDG uptake levels in the lungs. Gene enrichment over-representation analysis revealed that numerous biological processes were significantly enriched in the 639 genes, including several well known in TB transcriptomics such as platelet degranulation and response to interferon gamma, thus validating our novel approach. Others not previously associated with TB pathobiology included smooth muscle contraction, a set of pathways related to mitochondrial function and cell death, as well as a set of pathways connecting transcription, translation and vesicle formation. We observed up-regulation in genes associated with B cells, and down-regulation in genes associated with platelet activation. We found 254 transcription factor binding sites to be enriched among the 639 gene promoters. In conclusion, we demonstrated that of the 10,295 gene expression changes in peripheral blood, only a subset of 639 genes correlated with inflammation in the lungs, and the enriched pathways provide a description of the biology of resolution of lung inflammation as detectable in peripheral blood. Surprisingly, resolution of PTB inflammation is positively correlated with smooth muscle contraction and, extending our previous observation on mitochondrial genes, shows the presence of mitochondrial stress. We focused on pathway analysis which can enable therapeutic target discovery and potential modulation of the host response to TB.Pulmonary tuberculosis (PTB) is characterized by lung granulomas, inflammation and tissue destruction. Here we used within-subject peripheral blood gene expression over time to correlate with the within-subject lung metabolic activity, as measured by positron emission tomography (PET) to identify biological processes and pathways underlying overall resolution of lung inflammation. We used next-generation RNA sequencing and [ Mycobacterium tuberculosis and transmitted via inhalation of air droplets expelled by a person with active TB. The primary site of M. tuberculosis infection is the lung, which leads to pulmonary TB (PTB).Tuberculosis (TB) is among the leading causes of mortality due to infectious diseases worldwide, with 1.5 million deaths recorded in 2018 is a common PET tracer, and its accumulation in tissues of the body indicates enhanced glucose metabolism (Positron emission tomography-computed tomography (PET-CT) is a medical imaging method, in which PET provides functional and CT structural information \u201310. 18F-tabolism \u201317, whictabolism that is tabolism , 21 whil18F]FDG uptake levels. Most of these studies focused primarily on biomarker discovery by analyzing group differences between timepoints in peripheral blood data available from study subjects . Read pan 2.3.1d , and htson 0.6.0 was used package in R as an ordinal value; and j is the subscript for subject (n=75). Model 1 was used to extract the slope of each gene in each subject, while Model 2 constrains the expression levels of each gene to correlate with MSLA levels, over time, in each subject , such that the expression levels of the genes are correlated with PET levels, over time. Traditional differential gene expression analysis does not account for intra- and inter-subject variation.In the equations, subject , 64, and package in R veron 3.6.1 , 66, 67.on 3.6.1 , with th+ \u03b1\u03b2 T cells, CD14+ monocytes and neutrophils and modeled these using a leave-one-out approach.Adjusting for cell type proportion entails adding variables to the model and incurs a penalty in terms of the degrees of freedom. Increasing the model complexity can result in false negatives due to this penalty. Correction for a single cell type alone leaves the result poorly interpretable, since significance can be driven by changes in cell proportion in any of the remaining cell types. We therefore selected a set of 4 cell types, i.e., na\u00efve B cells, CD8We generated results for 5 different analyses based on Model 2:ijC omitted)2.1) Base, a model without correction for cell type B cell, a model correcting for CD8+ monocytes, and neutrophils2.3) CD8 T cell, a model correcting for na\u00efve B cells, CD14+ \u03b1\u03b2 T cells, and neutrophils2.4) Monocyte, a model correcting for na\u00efve B cells, CD8+ \u03b1\u03b2 T cells, and CD14+ monocytes.2.5) Neutrophil, a model correcting for na\u00efve B cells, CD8SetRank package in R for the set gene set enrichment analysis (GSEA) using thage in R , 71 and age in R for the package in R wit package and (c) bGestalt . For ORA the set . SetRankytoscape .SetRank output includes two rounds of correction with the Holm procedure. Since this second correction is dependent on the collection of pathways identified as enriched after applying the first correction, it is specific to the results for a given model. We therefore present the results for the comparison of models using only the p-values adjusted with the first correction.We merged the networks from all 5 models (2.1 to 2.5) into a single network to create a master layout of all enriched pathways. The network graph of each model was then represented using the master layout to generate per-model graphs with identical positioning of pathways for ease of comparison. Analyses controlled for false discovery using either the Benjamini and Hochberg or Holm ReMap to obtain the co-ordinates of the TF binding sites (TFBS). For each gene, we then extracted the TF binding site start (TFStart) and end (TFEnd), chromosome, TF, track, location, strand, gene transcription start site (GeneTSS), and symbol for a promoter of 4,000 bases upstream of the transcription start site of the target genes from human genome GRCh38.p13, using in-house scripts. To estimate over-representation of the TFs in PETGenes, we first extracted the TFBS and their genomic features from the list of PETGenes. Next, we calculated the counts of gene promoters containing the TFs. The counts are for gene promoters that have at least one TFBS for the TFs. Finally, we computed the TF over- or under- representation for a set of TFs comparing the frequencies in the query set (PETGenes) to that of the remaining genes in the reference (Human Genome), using Fisher\u2019s exact test and an FDR < 0.05 from ReMap, which includes transcription factors, transcriptional co-activator and chromatin regulators , generatR < 0.05 .We used the induced network module analysis in ConsensusPathDB , 79 to bTo identify biological processes underlying the resolution of lung inflammation, during PTB treatment, we first identified genes with significant changes in expression, over time, using Model 1. We refer to these as TimeGenes. Biological processes enriched in these genes reflect changes in transcript levels, over time, in response to PTB treatment. Next, using different forms of Model 2 (Models 2.1 to 2.5), we identified genes with expression levels significantly correlated with the changes in the PET metric MSLA, in patients who were considered cured at the end of the 6-month PTB treatment. Using GSEA, we could identify the biological processes and pathways associated with these genes that undergo changes in transcript levels in peripheral blood, and which correlated with inflammation in the lungs during PTB treatment.+ monocytes, CD16+ monocytes, CD4+ \u03b1\u03b2 T cells, CD8+ \u03b1\u03b2 T cells, CD56bright NK cells, na\u00efve B cells and neutrophils. The results from the ANOVA are shown in + \u03b1\u03b2 T cells, CD14+ monocytes and neutrophils, showed changes in proportions over time in a manner that suggested that they could influence the statistical model.We filtered cell proportions to remove cell types that did not reach a mean proportion > 0.05 at any time point. Seven cell types remained, namely CD14As a baseline analysis with which to compare our constrained analysis, we applied a simple model that identified transcripts that change over time. We identified 11,229 transcripts with significant changes in expression levels, over time, using Model 1 Table S118F]FDG uptake levels as represented by MSLA, over time, during PTB treatment genes between TimeGenes and PETGenes Table S4SetRank with the Reactome pathways Table S5CD19, VPREB3, CD72, CD22, FCRLA, CD79B, CD79A, HLA-DOB, P2RX5, FAM129C, FCRL5, PCDH9, BCL11A, PNOC, and BLNK. The expression profiles of PETGenes in Cluster 3, suggest up-regulation in B cells during treatment response, whereas Cluster 1, suggests down-regulation in platelet activation during treatment response. Curiously, there were no pathways overrepresented in Cluster 2 with the treatment-specific signature from Bloom et al. 320 micTable S6n et al. , 29 genen et al. , as well as their target genes and CALD1, GUCY1A1, GUCY1B1, ITGB5, MYL9, TPM1, TPM4, VCL. To these we added the genes whose nominal p-value contributed to the GSEA enrichment score: ACTA2, ANXA6, DYSF, MEF2A, MEF2C, MYH11, MYL12B, MYL6, MYLK, SORBS1, SORBS3, TLN1, TPM2, TPM3, as well as the transcription factors: CREB1, CREBBP, GATA1, GATA2, GATA4, GATA6, SRF, TEAD1, TEAD4. All but SORBS1, SORBS3, TPM2, and VCL decreased expression from Dx to W24. The network demonstrates that a highly interconnected cluster of contraction proteins connected to another interconnected cluster of transcription factors leading to generation of second messengers\u201d, and \u201cRUNX1 regulates transcription of genes involved in BCR signaling,\u201d whose function is restricted to B cells Table 4 + \u03b1\u03b2 cells). There are also several pathways identified here as potentially relevant to T cells that have not previously been identified. These include some of the phospholipid metabolism pathways and the PIP pathways.Eleven pathways, all consistent with different aspects of lipid and phospholipid metabolism are enriched in the model 2.3 \u201cCD8 T cell.\u201d The pathways are: synthesis of phosphatidic acid (PA); synthesis of dolichyl phosphate; fatty acid metabolism; synthesis of phosphatidylethanolamine (PE); beta oxidation of very long chain fatty acids; triglyceride metabolism; phospholipid metabolism; synthesis of phosphatidylinositol phosphates (PIPs) at the early endosome membrane; synthesis of PIPs at the late endosome membrane; PI metabolism; and triglyceride biosynthesis. Lipid metabolism has been established as important to the function of T cells , again s+ monocytes and neutrophils no pathway or collection of pathways provided support in the same way as for na\u00efve B cells and CD8+ \u03b1\u03b2 cells. The pathways identified are generally consistent with inflammatory processes, but not characteristic of the cell types.For CD142+; Smooth muscle contraction; G alpha I signaling events; Platelet activation signaling and aggregation; Cell surface interactions at the vascular wall; rRNA modification in the nucleus and cytosol; PD-1 signaling; and Interferon signaling and mitochondrial morphogenesis (TMEM11), but also includes many genes for mitochondrial complex V, the ATP synthase complex , which are all downregulated during treatment. Downregulation of these genes is consistent with the requirement of extensive oxidative phosphorylation during the peak of inflammation. Cells can increase oxidative phosphorylation by mitochondrial division or by increasing the density of cristae in mitochondria, which facilitates a higher density of oxidative phosphorylation complexes and enables mitochondria to be more efficient identified subtle significant changes in transcript levels that are ignored in traditional gene expression analyses and provide robust results for downstream differential expression analysis and clustering.Previous studies on TB treatment response , 28\u201330 hurements , 33, 34.Our study had some limitations. We used a linear-mixed effect model to analyze gene expression levels, which only considers linear correlation or relationship of gene expression with time. The linear-mixed effect model accounts only for the linear characteristics of measurements, ignoring other dynamics or patterns of gene expression and PET measurements which may be characteristic of TB. Additionally, transcriptomics only reveals changes in regulation of RNA levels which do not necessarily correspond to functional changes in proteins; nevertheless, it does provide insight into the regulatory responses, especially in longitudinal analyses. Lastly, the models correcting for cell proportions rely on computational deconvolution and not on differential counts, and the choice of which cell types to include in the models is difficult. Including too many variables (too many cell proportions) can weaken the inferential power of the models, and including cell types with little effect reduces power without any benefit. For future studies, we suggest using mixed-effect models with splines or other non-linear models with more time points. Another limitation is that PET-CT measures only glucose metabolism and not oxidative phosphorylation, nor does it provide a measure of bacterial burden; a direct measure of TB load would be ideal.18F]FDG uptake in the lungs, is positively correlated with down-regulation of genes enriched in \u201cplatelet activation\u201d, \u201cinterferon and interleukin signaling\u201d, and negatively correlated with up-regulation of genes enriched in \u201cB cell activation\u201d as well as many other pathways consistent with prior literature. These results validate our overall approach. In addition, we have shown that correcting for major cell type proportions using a leave-one-out approach allows identification of processes consistent with the remaining cell type. Lastly, we have identified \u201csmooth muscle contraction\u201d and pathways related to mitochondrial stress and dysfunction as highly enriched pathways. The extent of coordinated smooth muscle contraction gene expression suggests that the signal is derived from non-leukocyte origins, such as SPCs. The results obtained from our comprehensive pathway analyses provide important new insight into the pathobiology of TB. In future studies they could contribute to therapeutic target discovery and potential modulation of the host response to TB.In summary we have demonstrated that the resolution of inflammation in the lungs during TB treatment, measured with changes in PET-CT [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89403.Publicly available datasets were analyzed in this study. This data can be found here: Approval was obtained from the Health Research Ethics Committee (HREC) of Stellenbosch University (registration number N10/01/013), to recruit patients and collect specimens. For the current study to re-analyze the PET-CT and mRNA expression data, we received a separate HREC approval (X18/09/029). The patients/participants provided their written informed consent to participate in this study.Andr\u00e9 G. Loxton, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Annare Ellman, Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Bronwyn Smith, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Caroline G. G. Beltran, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Clifton E. Barry III, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Observatory 7925, South Africa; David Alland, Center for Emerging Pathogens, Department of Medicine, Rutgers-New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, United States; Friedrich Thienemann, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Observatory 7925, South Africa, Department of Medicine, Groote Schuur Hospital, Faculty of Health Science, University of Cape Town, Cape Town, South Africa; Gerard Tromp, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Gerhard Walzl, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; James M. Warwick, Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Jill Winter, Catalysis Foundation for Health, San Ramon, CA, United States; Katharina Ronacher, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Kim Stanley, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Ilse Kant, Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Lani Thiart, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Lance A. Lucas, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Laura E. Via, Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, South Africa; Lori E. Dodd, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland, United States; Magdalena Kriel, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Nelita Du Plessis, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Patrick Dupont, Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium, Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Ray Y. Chen, Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States; Robert J. Wilkinson, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, South Africa, Department of Medicine, Groote Schuur Hospital, Faculty of Health Science, University of Cape Town, Cape Town, South Africa, The Francis Crick Institute, London, United Kingdom, Department of Medicine, Imperial College London, United Kingdom; Shubhada Shenai, Center for Emerging Pathogens, Department of Medicine, Rutgers-New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, United States; Stephanie Griffith-Richards, Division of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Stephanus T. Malherbe, Department of Science and Innovation/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.TO and GT carried out the computational analyses and drafted the manuscript. GW designed the original study, obtained funding for it and oversaw the study. GT designed and supervised the current bioinformatic analysis reported here. SMa interpreted PET-CT and provided quantitative data on PET-CT scans as well as clinical findings. DZ, ET, and FD contributed to the NGS analysis. SMe provided expertise and additional supervision on computational analyses. EM, NP, AL, LK, KR, and GW provided expert immunological and clinical knowledge on interpreting the results. HK and JW interpreted results and participated in drafting the manuscript. All authors contributed to the article and approved the submitted version.TO, SM, GW, and GT were supported by the South African Tuberculosis Bioinformatics Initiative (SATBBI), a Strategic Health Innovation Partnership grant from the South African Medical Research Council and South African Department of Science and Technology. SMa received funding from the EDCTP2 program supported by the European Union (grant number CDF1576). GW received funding from the South African National Research Foundation (SARChI TB Biomarkers #86535) and the South African Medical Research Council. AL is supported by the NRF-CSUR (Grant Number CSUR60502163639) and by the Centre for Tuberculosis Research from the South African Medical Research Council (SAMRC). HK was supported by the Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa. The Catalysis Biomarker Consortium was funded by the Catalysis Foundation for Health, the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and the National Institute of Allergy and Infectious Diseases, International Collaborations in Infectious Disease Research.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the development of smart cities, there is a great emphasis on setting up so-called Smart City Control Rooms, SCCR. This paper presents Snap4City as a big data smart city platform to support the city decision makers by means of SCCR dashboards and tools reporting in real time the status of several of a city\u2019s aspects. The solution has been adopted in European cities such as Antwerp, Florence, Lonato del Garda, Pisa, Santiago, etc., and it is capable of covering extended geographical areas around the cities themselves: Belgium, Finland, Tuscany, Sardinia, etc. In this paper, a major use case is analyzed describing the workflow followed, the methodologies adopted and the SCCR as the starting point to reproduce the same results in other smart cities, industries, research centers, etc. A Living Lab working modality is promoted and organized to enhance the collaboration among municipalities and public administration, stakeholders, research centers and the citizens themselves. The Snap4City platform has been realized respecting the European Data Protection Regulation (GDPR), and it is capable of processing every day a multitude of periodic and real-time data coming from different providers and data sources. It is therefore able to semantically aggregate the data, in compliance with the Km4City multi-ontology and manage data: (i) having different access policies; and (ii) coming from traditional sources such as Open Data Portals, Web services, APIs and IoT/IoE networks. The aggregated data are the starting point for the services offered not only to the citizens but also to the public administrations and public-security service managers, enabling them to view a set of city dashboards ad hoc composed on their needs, for example, enabling them to modify and monitor public transportation strategies, offering the public services actually needed by citizens and tourists, monitor the air quality and traffic status to establish, if impose or not, traffic restrictions, etc. All the data and the new knowledge produced by the data analytics of the Snap4City platform can also be accessed, observing the permissions on each kind of data, thanks to the presence of an APIs complex system. This paper is organized as follows: Sect.\u00a0In most of the modern smart cities, there is a great emphasis on setting up the so-called Smart City Control Room (SCCR) that is an area in which all the data are collected and aggregated and where high-level data/results are summarized and made accessible for decision makers and city operators. In large metropolitan cities, the SCCR includes large panels/monitors on which the status of the city is displayed in real-time presenting predictions and alerts regarding: mobility, energy, social activities, the environment, weather, public transportation, people flow, health, water, security, ICT, governmental, first aid, civil protection, police, fire brigade, hospital triage, and thus almost all the city resources expressed via key performance indicators (KPI). Some of the city\u2019s monitored resources are representative of critical infrastructures such as: mobility and transport, energy, security, health, water, civil protection, governance, ICT, etc. In medium-sized cities, the daily management of city resources is performed by a set of city operators, which could be legally independent with respect to the central municipality and should autonomously manage their SSCR are instruments for the development and implementation of technology to accelerate innovation in cities any kind of data source/collector, protocol and format from/to: open data, real-time data, GIS, IoT data, data stream, data driven, social media, Industry 4.0, etc.; (ii) IoT devices and networks, IoT edges, gateways, IoT brokers, via various protocols and formats; (iii) Web-scraping processes; (iv) dashboards collecting actions from the users via: buttons, dimers, time selectors, and showing them; (v) mobile applications collecting and presenting; (vi) results of data analytics, including personal data produced by users . They can be put in execution IoT edge, as well as on Cloud, and are based on Node-RED. IoT app also enables to perform business logic , smart interaction and data transformation behind the Snap4City dashboards, integrating ticketing, video wall dynamic re-configuration, etc. Microservices may also manage processes for data analytics, Web scraping, external services, data gathering and publication, etc. , formats , and protocols in push and/or pull, etc. This is the reason why a smart city big data platform, such as Snap4City, must be flexible and capable to ingest every various different kinds of data see Fig.\u00a0.Fig. 3SnMobility: public transport operators schedule and paths, traffic-flow sensors, parking status, cycling paths, road graph, accidents and traffic events, ordinances, car-park occupancy prediction, what-if routing, quality of public transportation services, etc. The services produced, starting from those data are: KPI assessing quality of public transportation; routing and multimodal routing; real-time traffic-flow reconstruction ; real-time status and predictions for parking, smart parking;Environment: (i) irrigators; (ii) smart waste; (iii) air quality sensors: PM10, PM2.5, CO, benzene, NO, NO2, O3, temperature, humidity, etc.; (iv) air quality heat maps for pollutants at point (iii); and (iv) pollination. As derived data, we can have NOX predictions ; air quality heat maps updated every hour, real-time status and trends related to air quality sensors and pollination, NOX predictions for the next 48\u00a0h, with a resolution of 4\u00a0\u00d7\u00a04\u00a0m and at two levels of height (at 3 and 6\u00a0m); and long-term predictions for pollutants\u2019 critical days;Energy: (i) recharging stations (fast and regular); (ii) consumption meters (smart info); (iii) smart light; monitoring consumption via smart meters, smart lights status and trends;Weather: forecast and actual ;Social: (i) smart benches; (ii) entertainment events; (iii) Twitter monitoring via Twitter vigilance (https://www.disit.org/tv), sentiment analysis, NLP text; (iv) TV-camera streams; and (v) triage status of major hospitals; also for early warning.People Flows: (i) Wi-Fi status; (ii) origin-destination matrices, people-flow analysis from the Wi-Fi network of access points;Governmental and Communications: (i) KPI of the city, including COVID-19 data; (ii) digital signage (not directly included into the solution for Florence); (iii) civil protection, resilience guidelines and suggestions, KPIs (RESOLUTE project);Tourism and Culture: Points of interests (POI), cultural events, etc.;Analysis: (i) what-if routing; (ii) scenarios; (iii) traffic flow; and (iv) environmental predictions.Video streams: (not directly included into the Snap4City solution for Florence).Once the data have been collected and integrated, the historical data and real-time data can be exploited by data analytics processes, IoT apps, dashboards and apps. The original data and results of the data analysis can be accessed for business intelligence tools and SCCR. The most relevant data available in the Florence SCCR, are described next and classified based on their context:Starting from these kinds of data, reworking them and thanks to the APIs presence, a set of services is available in the Florence SCCR. The series of dashboards designed to provide the services just described, a mobile app was created and called \u2018Florence where what\u2026\u2019 (see next section) and are capable to send suggestions and recommendations based on location and the preferences expressed by citizens and tourists.manage the data collection and integration, data analytics, prediction indicators , but also to carry out simulations and comparing them with the hypotheses on events, realized before the simulation and without the Snap4city tools.Activate and run data-analytic algorithms that can produce systematic or, if necessary, real-time forecasts, identifications of anomalies, and the ability to communicate them to operators and from an early warning and study perspective. Therefore, they are able to generate reports even in advance.Visualize the state of the city and its evolution and critical aspects for the different operators , allowing also some remote operators in their offices to access some summary information, prediction, service status, etc.Enable the carrying out, directly on the dashboards, the necessary in-depth analysis with drill-down techniques (time space and for reports), with: What-if simulations on problems and solutions, routing algorithms, predictive models and in-depth analysis tools. On these, it must be possible to open discussions/chats with other operators, even remote ones , and to bring the attention of all operators to support decisions.Manage events and reports that may arrive from various operators: mobility, transport, waste, energy, social media, highways, public transport, etc., in various standards and through various communication channels. Managing in these cases means: coordinating possible joint actions between several operators, acting, following their evolution, and keeping track of events, until their conclusion/resolution, to take them into account for the next actions.A SSCR is a solution and structure in which all data and indicators of the city are collected and aggregated to produce summary visions, indicators, forecasts, precursors, anomaly indicators, etc. The results are produced through big data analytics to support decision makers and operators, so that they can quickly understand the situation in full and act, also through simulations for scenarios with what-if conditions. When the city grows, its systems become more complex. Moreover, some cities are morphologically complex during their histories, morphogenesis and structures, and it becomes important to:Main dashboard, \u2018Firenze Oggi\u2019 (Florence Today), contains a set of KPIs monitored in real time: a number of users connected to the public Wi-Fi, civil-protection messages, weather forecasting, recharging stations statuses, state of road maintenance and accidents, public transport lines; but also statistical data such as: census numbers and analyses of: traffic, pollution and what-if analysis. It has links to the following dashboards.Energy: position on the city map, real-time status and historical trends of: fast and normal recharging stations, ZTL gates, Wi-Fi, smart irrigators, smart lights, statistics on residential smart energy meters. KPIs: monthly cumulative energy consumption, average weekly consumption of each fast recharging station, number of users connected to the mobile app, eEnergy consumption via mobile app, accumulator status (used), etc.Environment: position on the city map, real-time status and historical trends of: air quality stations and low-cost sensors (PM10), weather sensors, pollen monitoring, Florence weather for today and for the next two days , temperature, waste sensors, etc.Mobility: traffic events in Florence, traffic daily inflow/outflow trend, total number of inflow/outflow vehicles, car-park statuses and trends, etc.Social: Twitter sentiment trends in the city of Florence, natural-language processing and sentiment analysis on tweets , people flow.Resilience: civil-protection messages in real time, hospital first aid, evacuation paths, etc.The SCCR is a decision-support tool that is able to provide evidence of the arrival/occurrence of critical conditions in real time and/or precursors of such conditions and offer solutions . Following these guidelines, the Florence SCCR has been realized with a series of ad hoc dashboards connected each other:Moreover, other additional views can be opened. In Fig.\u00a0The Florence SCCR development started on 2017 with the first dashboard, and since that time, the number of data has been increased with corresponding views and dashboards of various kinds. Most of the data are public and accessible on dashboards from the Web site of Snap4City.org, while a number of dashboards are private to the municipalities. In Fig.\u00a0The attention on general aspects, mobility and environment are a confirmation of the effective usage and need of an instrument such as an SCCR for monitoring the city. In summary, a total of more than 6000 accesses have been made and 340,000\u00a0min have been spent on the major dashboards for the major areas in the year 2019, which is an average of 57\u00a0min per access. On the other hand, there are dashboards that are typically accessed 24H/7D, and those that are only sporadically used.Smart City Control Rooms, SCCRs, are getting strong attention at this time for their capability of reporting in real time the status of several city aspects, thus creating a strong and effective tool for decision makers. This paper presented Snap4city as a Big Data Smart City Platform to support the city decision makers by means of a SCCR. The solution is adopted in different degrees of diffusion in European cities such as Antwerp, Florence, Lonato, Pisa, Santiago de Compostela, etc. In this paper, the Florence SCCR has been analyzed as a major use case describing the data, the services and the workflow. For data aggregation, the Km4City multi-ontology and tools have been used to collect data from GIS, utilities, open data, IoT networks, external services, social media, etc. The first Florence SCCR dashboard appeared in 2017 as a prototype, and, since that time, a great evolution has been occurred and the amount and type of data have increased. Most of the data are public and accessible on dashboards from the Web site of Snap4City.org, while a number of dashboards are private to the municipality. The results presented have shown the data regarding the last year of high usage of the platform. During this period, a particular attention by the users, on general overview aspects, mobility and the environment have been registered. In summary, a total of more than 6000 accesses have been made and 340,000\u00a0min have been spent on the major dashboards for those major areas in the year 2019, which is an average of 57\u00a0min per access."} +{"text": "In \u201cDocumenting Social Media Engagement as Scholarship: A New Model for Assessing Academic Accomplishment for the Health Professions\u201d :e25070), one of the authors was not mentioned in the original paper.The following author has been added:Alice Eaton, BscSwansea University Medical School, Swansea, United KingdomOne of the contributors was missed in the Acknowledgement section. Previously, the Acknowledgement section read as follows: All authors met the ICMJE authorship criteria, including reviewing and approving this manuscript for publication. Each of the 40 coauthors completed an Authorship Attestation Form confirming that they met all 4 of the ICMJE authorship criteria. In addition, each coauthor described on a shared Google Sheet how they made \u201csubstantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data.\u201d The authors wish to thank Jocelyn C Anderson, PhD, RN, S Alexander Kemery, PhD, RN, and Chrystal L Lewis, PhD, RN for their comments on the draft of this manuscript.The corrected Acknowledgement section now reads as follows: All authors met the ICMJE authorship criteria, including reviewing and approving this manuscript for publication. Each of the 40 coauthors completed an Authorship Attestation Form confirming that they met all 4 of the ICMJE authorship criteria. In addition, each coauthor described on a shared Google Sheet how they made \u201csubstantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data.\u201d The authors wish to thank Jocelyn C Anderson, PhD, RN, S Alexander Kemery, PhD, RN, Rebecca Koszalinski PhD, RN, CRRN, CMSRN, and Chrystal L Lewis, PhD, RN for their comments on the draft of this manuscript.The affiliation for authors Brendan Huang and Ajay Major was incorrect. They were displayed as:Brendan HuangDepartment of Clinical Neurosciences, Tulane University, New Orleans, LA, United States Ajay MajorUniversity of Chicago, Section of Hematology and Oncology, Chicago, IL, United StatesThey have been updated to:Brendan HuangDepartment of Neurology and Neurosurgery, Tulane University, New Orleans, LA, United StatesAjay MajorSection of Hematology and Oncology, University of Chicago, Chicago, IL, United StatesThe correction will appear in the online version of the paper on the JMIR Publications website on December 9, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "In \u201cDiagnostic Accuracy of Chest Computed Tomography Scans for Suspected Patients With COVID-19: Receiver Operating Characteristic Curve Analysis\u201d :e19424), the authors noted one error.The affiliation for authors Lianpin Wu, Qike Jin, and Jiawei He was incorrectly listed as:Department of Cardiology, Wenzhou Medical University, Wenzhou, ChinaThe affiliation for these authors has been corrected to:Department of Cardiology, the Second Affiliated Hospital & Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou, ChinaThe correction will appear in the online version of the paper on the JMIR Publications website on November 20, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Author Contributions statement appears below.An author name was incorrectly spelled as \u201cMichael von Bergwelt.\u201d The correct spelling is \u201cMichael von Bergwelt-Baildon\u201d. The updated \u201cMT, SYY, and CB developed the conception and design of the study. MT, SYY, TP, AB, and HG discussed the cases in interdisciplinary panels. MT acquired patient data. MT and SYY organized the database, performed all analyses, and wrote the first draft of the manuscript. SYY, TP, and AB acquired the imaging data. TP, HG, MS, ST, MB-B, JM, JH, EC, SM, and CB contributed to the manuscript. All authors contributed to the revision and read and approved the submitted version.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-019-57087-2, published online 14 January 2020Correction to: The original version of this Article contained a typographical error in the spelling of the author Jooho Lee, which was incorrectly given as Jooho lee.In addition, the original version of this Article contained an error in Affiliation 6, which was incorrectly given as \u2018Department of Chemistry, Chonbuk National University, Jeonju, 54896, Republic of Korea\u2019. The correct affiliation is listed below:Department of Chemistry, Jeonbuk National University, Jeonju, 54896, Republic of Korea.These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "In the last 3 months, nearly a third of the world's population has changed their lifestyle. At this time of writing (June 30th) the COVID-19 pandemic has left a total of 10.302.867 confirmed cases, with more than 505.518 deaths worldwide, spreading to more than 188 countries and Sociedade Brasileira de Urologia (SBU) performs this special edition, which aims to provide a screenshot impact of the COVID-19 Pandemic on Urology, within each different area of development It's contains a total of 27 manuscripts performed by expert urologists from France, Italy, Spain, Iran, Germany, Argentina, Uruguay, Brazil, Mexico, Peru, Bolivia, Panama, the USA. The information that it contains, is reported until May 8th 2020.Finally, I would like to thank each colleague participating in this project, for the effort and valuable academic contribution, hoping that this crisis we are going through will allow us to grow as people and professionals. \u201cEvery crisis has a solution and a learning process, this only depends on us\u201d"} +{"text": "While there is an academic dialogue around what the field entails, developing from its roots of hygiene & tropical medicine and international health, there is still room for enhanced understanding and refined scope . This isth Canadian Conference on Global Health (CCGH), convened virtually from October 19 to 22, 2020 by the Canadian Society for International Health, was a key venue for further examining the different facets of global health. Featuring renowned speakers from numerous sectors, such as Drs. Jane Goodall, Anthony Fauci, and Tedros Adhanom Ghebreyesus, discussions ranged greatly from the humanitarian response to COVID-19 to changing politics. The conference allowed for a reimagined understanding of the field and paved the way to a broader understanding that included three emerging prospects: emphasizing the importance of policy and governance, encouraging engagement of participants from the global south, and elevating the voice of women.The recent 26he present global health crisis is not primarily one of disease, but of governance: its key characteristic is a weakening of public policy and interstate mechanisms as a consequence of global restructuring\u201d th CCGH delivered virtually afforded opportunities for over a thousand participants from around the world to attend; drawing participation from: Afghanistan, Algeria, Argentina, Bangladesh, Belgium, Benin, Botswana, Brazil, Burkina Faso, Cameroon, Canada, Colombia, Costa Rica, Democratic Republic of the Congo, Denmark, Dominican Republic, France, Gambia, Georgia, Germany, Ghana, Guinea, Ethiopia, Egypt, Haiti, Honduras, Hungary, India, Indonesia, Iraq, Kazakhstan, Kenya, Libya, Madagascar, Malaysia, Malawi, Mali, Mexico, Morocco, Mozambique, Myanmar, Nepal, Netherlands, Nigeria, Pakistan, People\u2019s Republic of China, Peru, Philippines, Portugal, Rwanda, Saint Lucia, Senegal, Spain, Somalia, South Africa, South Sudan, Sri Lanka, Switzerland, Turkey, United Republic of Tanzania, Uganda, United Kingdom of Great Britain and Northern Ireland, United States of America, Viet Nam, Zambia, and Zimbabwe. With more diverse voices and perspectives from around the world, global health practice can be improved. This is particularly the case with different cultures which may have different understandings and perspectives, which draw upon different traditions of social justice [The 26 justice . For exa justice . Given t justice .The BMJ Gender Diversity Group that women were underrepresented in decision-making around COVID-19 [th CCGH unveiled the 2020 Canadian Women in Global Health list, \u201cshowcasing the incredible achievements of Canadian women leaders in global health, fostering new and exciting collaborations, and advocating for gender equity in the health workforce and leadership more broadly\u201d [Similarly, with 49.6% of the global population identifying as female in 2017 , which dCOVID-19 . The 26tbroadly\u201d . For insbroadly\u201d . The lisOverall, I must commend the CCGH and its organizers for outlining three emerging prospects for which global health can be reconsidered. With enhanced attention paid to global health, we can reform our approaches, through emphasizing the importance of policy and governance, encouraging engagement of participants from the global south, and elevating the voice of women, to ultimately enhance public health to protect populations and improve public health."} +{"text": "Many studies find gender differences in how older adults\u2019 report on their memory, perform on cognitive testing, and manage functional impairments that can accompany cognitive impairment. Thus, understanding gender\u2019s effects in aging and Alzheimer\u2019s research is key for advancing methods to prevent, slow, manage, and diagnosis cognitive impairment. Our study, CoGenT3 \u2013 The study of Cognition and Gender in Three Generations \u2013 seeks to disambiguate the effects of gender on cognition in order to inform a conceptual model, guide innovations in measurement, and support future study. To accomplish this ambitious goal, we have gathered an interdisciplinary team with expertise in psychology, cognition, sexual and gender minorities, library science, measurement, quantitative methods, qualitative methods, and gender and women\u2019s studies. The team benefits from the intersections of expertise in being able to build new research ideas, gain novel insights, and evaluate a wide-range of actions and re-actions but this novelty can also raise challenges."} +{"text": "This research note aimed to analyze the scientific productivity trends 2015\u20132019, focusing on the top 30 universities in Europe and United States and on the top 30 private companies\u2014as classified in the SCImago Institutions Ranking. Our hypothesis is that private companies are gaining an increasingly prominent role in the research field, while academia is losing its predominance.From 2015 to 2019, all universities in Europe and the United States lost positions in the scientific production ranking, while private companies gained positions. These trends seem to be driven mainly by the scientific productivity sub-indicator \u201cInnovation\u201d. These data suggest that the role private companies will play in the future will not be limited to support research economically or influence it from \u201coutside\u201d. Private companies have taken a path that may lead them to directly control all stages of production/communication of knowledge, including research\u2014a role once bestowed on universities. Our data, although preliminary, seem to suggest that, at present, academia risks losing its predominance in the research field. This scenario deserves attention because of the threats it may pose to the independence of research and its role in supporting human equity and sustainable health for all. Scientific research has always had a fundamental role in promoting health and the progress of society as a whole. A recent editorial published in The Lancet has discHowever, we think that also an alternative\u2014more pessimistic\u2014scenario, emerging from an analysis of recent trends in scientific productivity, deserves attention because of the threats it may pose to the independence of research and its role in supporting human equity and sustainable health for all.In support of this hypothesis, we will (1) provide an analysis of the scientific productivity trends from 2015 to 2019, focusing on the top 30 universities in Europe and the United States and on the top 30 private companies (2) detail the methodology used and its limits, and (3) discuss the implications of our hypothesis and future addresses.We have analyzed the scientific productivity trends from 2015 to 2019. First, we used the SCImago institutions ranking . InnovatWe calculated the average position (\u00b1\u2009standard deviation) in the ranking for scientific productivity by group for each year from 2015 to 2019. We then calculated the changes of positions in the ranking for scientific productivity by group from 2015 to 2019.To see if these changes of positions in the ranking for scientific productivity were significantly different between universities in Europe and universities in the United States vs. private companies, we performed a multivariate Kruskal\u2013Wallis test \u20137. All sIn Europe, the top 30 universities were: Oxford, University College London, University of Cambridge, Imperial College London, Swiss Federal Institute of Technology, Catholic University of Leuven, University of Copenhagen, Utrecht University, University of Amsterdam, Kings College London, University of Manchester, University of Edinburgh, Karolinska Institute, Ecole Polytechnique Federale de Lausanne, Sorbonne Universite, Ghent University, Technische Universitat Munchen, University of Groningen, Leiden University, VU University Amsterdam, Universit\u00e0 degli Studi di Roma La Sapienza, Aarhus University, Ludwig-Maximilians Universitat Munchen, Erasmus University Rotterdam, Lunds University, Ecole Pratique des Hautes Etudes, University of Helsinki, Universitat Zurich, Uppsala University, and Technical University of Denmark. In the United States, the top 30 universities were: Harvard University, Harvard Medical School, Massachusetts Institute of Technology, Stanford University, Johns Hopkins University, University of Michigan Ann Arbor, University of Washington, University of Pennsylvania, University of California Los Angeles, Columbia University, University of California San Diego, University of California Berkeley, Cornell University, University of California San Francisco, Yale University, Duke University, University of Wisconsin Madison, University of Minnesota Twin Cities, Northwestern University Evanston, University of North Carolina Chapel Hill, University of Maryland Baltimore, New York University, University of Pittsburgh, Ohio State University Columbus, University of California Davis, University of Southern California, University of Chicago, Pennsylvania State University, University of Florida, and Washington University in Saint Louis. The top 30 private companies operating in Europe and in the US or at the global level were: Google, Facebook Inc., Microsoft Corp, Microsoft USA, Samsung Corp, Regeneron Pharmaceuticals Inc, Hoffmann-La Roche Ltd. United States, Hoffmann-La Roche, IBM United States, Genentech Inc., IBM Research, Alphabet Inc, Novartis Institutes for Biomedical Research United States, Microsoft Research Cambridge, MedImmune LLC., Toyota Group, Nokia Corp, Nokia Finland, GlaxoSmithKline United States, Qualcomm Inc USA, Qualcomm Inc, Sanofi United States, Biogen Idec USA, NEC Corp, Biogen Idec, Novartis, GlaxoSmithKline, Panasonic Corp, LG Corporation, and Pfizer Inc. United States.From 2015 to 2019, all the universities in these groups lost positions in the scientific production ranking. In Europe, universities lost on average \u2212\u20099.8\u2009\u00b1\u200974.2 positions, while in the United States \u2212\u20095.5\u2009\u00b1\u200921. On the contrary, private companies gained on average +\u2009129.9\u2009\u00b1\u2009143.9 positions.These trends seem to be driven mainly by one of the scientific productivity sub-indicators, \u201cInnovation\u201d. Indeed, if we analyze this specific sub-indicator, the trends are even more marked. Universities lost \u2212\u2009166.6\u2009\u00b1\u200960.6 positions on average in Europe, and \u2212\u2009114.7\u2009\u00b1\u200951.5 positions in the United States; while private companies gained +\u2009116.5\u2009\u00b1\u2009113.7 positions.p value\u2009<\u20090.0001).On average, the European universities had higher positions than private companies in the ranking in 2015 . The scientific productivity trend from 2015 to 2019 was significantly different between these two groups and in 2019 (46.8\u2009\u00b1\u200927.5 vs. 107.9\u2009\u00b1\u200951). However, again, the scientific productivity trend was significantly different from 2015 to 2019 in these two groups .Our data, although preliminary, seem to suggest that, at present, academia risks losing its central role in the research field, while private companies are gaining prominence.It is interesting that, among private companies, sectors historically linked to research have lost power in terms of scientific productivity. In contrast, companies specialized in internet-related services, technology, and data analytics have acquired increasing importance in the research field. Alarmingly, some of these companies, at present in the top ranking for scientific productivity, have recently been accused of using the information they gather from individuals indiscriminately and amorally for the purposes of profit-making and, even worst, social control , 10.The trends above analyzed suggest that the role private companies will play in the future will not be limited to support research economically and/or influence it from \u201coutside\u201d. Indeed, companies specialized in internet-related services, technology, and data analytics have taken a path that may easily\u2014or already has\u2014lead them to directly control all stages of production and communication of knowledge, including research\u2014a role once bestowed on universities. This finding is in contradiction with the results of a recent study by Fleming et al. , which sAlthough caution is needed given the preliminary nature of our data, the trends analyzed seem to suggest that, at present, academia is losing predominance in the research field. The vision matured in the nineteenth-century of universities (and science) as expression of free thought, guarantee for rights, and ability to dialogue with power to further human development and social justice is apparently going through a historic crisis.If the trends analyzed will be confirmed, the pessimistic vision of the Dialectic of Enlightenment may becoThe present research note discusses the findings of an analysis of trends in scientific productivity. This is a preliminary work using a simple methodology.The results of our analysis need to be confirmed using a bigger sample size and data from other geographical areas or specific research fields.Future research should examine all the scientific productivity sub-indicators: not only \u201cInnovation\u201d but also \u201cNumber of published articles and citations\u201d and \u201cSocial media visibility\u201d.Furthermore, future studies should investigate how the cooperation between universities and private companies may influence scientific productivity and, in turn, the ranking.Finally, it would be critical to have data from sources other than SCImago. Currently, SCImago is the only dataset grouping data by research institution, while similar databanks do not provide this kind of information."} +{"text": "A community has many different opportunities to improve the traffic safety. The community is local part of the public sector. On all decision made has the community big impacts on questions within its own territory. Urban planning is an important tool. Urban planning is normally a rather complex system and important decisions are made in a long term perspective. It is very important for all who work for traffic safety to learn the system in order to have an impact. The big pallet a community has embrace also many other tools than urban planning.1. Reduce the need of transportation: Urban planning, public transportation, road toll, forbid use of cars in some areas, one-way roads, reducing parking places 2. Separation of areas for activities: Special lines for pedestrians, bikes, cars and public transportation 3. Safety in the road system: Roundabout, fens, avoid U-turns, street lightning, traffic light, sleeping policemen4. Maintaining of the infrastructure: No digging technics, cleaning streets from snow fist for pedestrians5. Supervision: Speed control, immediate feed-back to offenders. Camera supervision, Control of parking, Alco control, Control the use of helmets, belts etc., Control of vehicles 6. Local regulations: Speed limits, one way roads, parking regulations, no access for cars and motorbikes to some areas, the high of hedges, restrictions for traffic during some time during the day7. Education and Information: Special parks for education of children, education and information in preschools and schools, education for old citizens8. Support to different groups: Baby and child seats for rent, helmets for rent, reflectors, bus-service for elderly9. Volunteers: Follow children to and from school, give advice to all in traffic, help the police in their supervision10. Support to local sport-clubs and other associations11. Restaurants and alcohol beverages: Restrictions to serve drivers alcohol, education to serving personnel, home driving service12. Agreements with employees and tenders: Use of safety helmets, belts etc., intelligent speed adaptation (ISA), always give priority to public transportation or bike, use only safe cars with alcohol-interlockCity Planning, Governing, Safe Community"} +{"text": "Acanthobothrium have been documented as parasites of the spiral intestine of elasmobranchs. Results of a metadata analysis indicate that 114 species of elasmobranchs have been reported as hosts of 200 species of Acanthobothrium. The metadata analysis revealed that 3.7% of species of sharks and 14.9% of species of rays that have been reported as hosts to date; some species are parasitized by more than one species of Acanthobothrium. This work provides a Category designation, as proposed by Acanthobothrium. These Category designations are a tool to facilitate comparisons among members of Acanthobothrium for descriptions of new species in the future.Species of According to Acanthobothrium Blanchard, 1848 is the most diverse genus that has been reported as parasite of the spiral intestine of elasmobranchs (Caira and Jensen 2017). At the present time, 201 species of Acanthobothrium are considered to be valid are host to a great variety of parasites in nature, particularly helminths. be valid , 2020. TAcanthobothrium and their geographic distribution based on records that have been generated from different parts of the world. The checklist focuses on the 201 valid species of Acanthobothrium and reports correlated with the genera and species of elasmobranchs, and includes the geographical distribution of each.The main goal of this work is to provide a revised checklist based on a metadata analysis of the host relationships of members of Acanthobothrium continues to grow and there are still regions of the world without a single report of this genus Ocean;WCA Western Central Atlantic;WCP Western Central Pacific;WIO Western Indian Ocean;WNA Western North Atlantic;WNP Western North Pacific;WSA Western South Atlantic;WSP Western South Pacific.Acanthobothrium presented herein includes the name of the species, authority , abbreviation of the name of the collection where specimens are deposited and the accession numbers of the specimens, followed by the status of the specimens . The acronym \u201cNR\u201d was used for data that are not reported in the original source. Localities were given and referenced in the literature cited. A Category designation was supplied for all species using the categorical method proposed by Information for each species of Acanthobothrium based on the combination of four qualitative characters: the total length of worms- \u2264 15 mm = S (short) or > 15 mm = L (long); the number of proglottids comprising the strobila- \u2264 50 = F (few) or > 50 = M (many); the number of testes per proglottid- \u2264 80 = F (few) or > 80 = M (many); and symmetry of the ovarian lobes- symmetrical = S or asymmetrical = A. Of the possible combinations the following 10 categories currently are recognized and coded as follows: 1 = SFFS; 2 = SFFA; 3 = LMMA; 4 = LMMS; 5 = LMFS; 6 = LMFA; 7 = LFFA; 8 = SMFS; 9 = LFFS; 10 = SMMS. This method limited the number of necessary comparisons required in the description between known species with new species assigned to the same Category. For this work, the categories and characteristics were used as in The categorical method was developed as a system of grouping species of For specimens deposited in a formal collection, acronyms are as follows:AMSAustralian Museum, Sydney;CH-MHNJP Colecciones Helmintol\u00f3gicas del Museo de Historia Natural \u201cJavier Prado\u201d y del Instituto de Medicina Tropical \u201cDaniel. A. Carri\u00f3n\u201d, Universidad Mayor de San Marcos, Per\u00fa;CHE Colecci\u00f3n de Helmintos, Centro de Investigaciones Biol\u00f3gicas, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca, M\u00e9xico;CHIOCCole\u00e7\u00e3o Helmintol\u00f3gica do Instituto Oswaldo Cruz, Rio de Janeiro, Brazil;CNHE Colecci\u00f3n Nacional de Helmintos del Instituto de Biolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, M\u00e9xico;DMNZ Dominion Musem , New Zealand;DZAUW Department of Zoology, Andhra University, Waltair, India;DZCJ Department of Zoology, Bipin Bihari, P. G. College, Jhansi, India;HWMLUniversity of Nebraska State Museum, Harold W. Manter Laboratory, Division of Parasitology, Lincoln, Nebraska, United States;IPCAS Institute of Parasitology, Academy of Sciences of the Czech Republic, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic;IPMB Institut Penyelidikan Marin Borneo (Borneo Marine Research Institute), Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia;LRP Lawrence R. Penner Parasitology Collection, Helminthological Collection, University of Connecticut, Storrs, Connecticut, United States;MACN-PaMuseo Argentino de Ciencias Naturales, Colecci\u00f3n Parasitol\u00f3gica, Buenos Aires, Argentina;MEPN Museum of the Escuela Politecnica Nacional, Quito, Ecuador;MHNLSMuseo de Historia Natural La Salle, Caracas, Venezuela;MHNP Museo de Historia Natural, Lima, Peru;MLP Museo de Ciencias Naturales de La Plata, Departamento de Zoolog\u00eda Invertebrados (Parasitolog\u00eda), Argentina;MNHG Museum of Natural History, Geneva, Switzerland;MNHN Mus\u00e9um National d\u2019Histoire Naturelle, Paris;MNHNCMuseo Nacional de Historia Natural de Chile;MPM Meguro Parasitology Museum, Tokyo, Japan;MZUM (P) Muzium Zoologi, Universiti Malaya, Kuala Lumpur, Malaysia;MZUSPMuseu de Zoologia da Universidade de S\u00e3o Paulo, Brazil;NHMUKThe Natural History Museum, London;NMNS National Museum of Natural Science, Taichung, Taiwan;PRLXUParasitology Research Laboratory, Xiamen University, China;QMQueensland Museum, Brisbane, Queensland, Australia;SAM AHCSouth Australian Museum, Adelaide, Australia;SBC Sarawak Biodiversity Center, Kuching, Sarawak, Malaysia;SPUKSchool of Parasitology, Department of Zoology, University of Karachi, Pakistan;SYSU School of Life Sciences, Sun Yat-sen University;UAA Department of Zoology, University of Allahabad, Allahabad, India;USNPCUnited States National Parasite Collection, Beltsville, Maryland, United States;ZCUOK Zoological Collection, University of Kurdistan, Sanandaj, Iran;ZIMC Collection of the Zoological Survey of India, Indian Museum, Calcutta and the Collection of the Department of Zoology, the University of Allahabad, India;ZMB Natural History Museum Berlin, Germany;ZUTCCollection of the Zoological Museum, University of Tehran, Tehran, Iran.Acanthobothrium. The list includes the type host of each species, type locality, and additional hosts and/or localities. Five of the elasmobranchs that were reported as hosts of Acanthobothrium were only identified to genus and four others are reported as \u201ccf.\u201d (= similar to) , Heterodontidae (five species) and Triakidae (six species) and Dasyatidae (70 species) Fig. . In contium Fig. . Of the es) Fig. .Acanthobothrium are not evenly grouped in the different categories. In Category 1 there are 55 species, 44 in Category 2, 19 in Category 3, 37 in Category 4, 17 in Category 5, 14 in Category 6, four in Category 7, four in Category 8, and three in Category 9. Although there is a Category 10, species in that category also are in grouped with those in Category 8 because their characteristics are thought to fall into both categories (Table Acanthobothrium were classified as unknown (\u201c?\u201d) because the original descriptions do not have sufficient information for assignment in one of the ten categories have been reported as hosts for species of ium Fig. . In contium Fig. . Estimatreported . PublicaECA, ESA, WIO, ARC, and SOC. According to the percentages of species of elasmobranchs that have been reported as hosts of species of Acanthobothrium, we can infer that there are still many new species of Acanthobothrium to be discovered. In the GenBank database records, molecular sequences of only 16 of the 201 species of Acanthobothrium have been reported. However, more molecular information about species of Acanthobothrium is required for future analyzes, both for identification and life cycle studies; these would provide more solid information for delimiting distributions.The information in the Figures Acanthobothriumchilensis R\u00eago, Vicente & Herrera, 1968, was included for reference, although it was described from a fish, Sardachiliensis (Perciformes: Scombridae) see . Extensidae) see failed tAcanthobothrium appear to exhibit oioxenous specificity for their elasmobranch hosts. In the present metadata analysis, for species exclusively in elasmobranchs, 83% of the species of Acanthobothrium show remarkable host specificity for their definitive host, and thus, should be considered to be an oioxenous species. In contrast, 34 of the 200 species (17%) of Acanthobothrium have been reported in more than one species of elasmobranch (Table Acanthobothrium, 45 of the type specimens of Acanthobothrium require confirmation of the host (Table Acanthobothrium that suggest misidentification of the parasites; these should reevaluated in future studies. To mention obvious cases, A.batailloni has been reported from the Mediterranean Sea and from the Pacific coast of Peru and Chile and A.brevissime has been reported from the Gulf of Mexico and the Pacific coast of Peru.According to species 7% of Aca species 7% of AcaAcanthobothrium, 13 have been classified in more than one category (see category designations in Table The categorical method developed by Acanthobothrium that has been assigned to more than one category suggests that the categories still need some refining, or it is an example of cryptic species that cannot be distinguished without molecular information. However, molecular information cannot replace morphological descriptions of species. One reason is the lack of material for sequencing of the vast majority of already-known species. Morphology also augments molecular data in studies of the phylogeny of platyhelminths (Acanthobothrium. This updated database includes the category designation for each species described to date will be an important tool for the future taxonomic studies.Having more information, such as molecular sequences, could solve some problems in identification, such as the two cases mentioned above. A species of elminths . A compl"} +{"text": "In \u201cTwelve-Month Follow-Up to a Fully Automated Internet-Based Cognitive Behavior Therapy Intervention for Rural Adults With Depression Symptoms: Single-Arm Longitudinal Study\u201d :e21336) the authors noted one error.The affiliation for authors Mark Schure and Kathryn Tuchscherer Franklin was incorrectly listed as:Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT, United StatesThe correct affiliation for these authors is:Department of Health & Human Development, Montana State University, Bozeman, MT, United StatesThis affiliation is affiliation 1 in the corrected manuscript. Accordingly, affiliations 1 and 2 in the originally published manuscript have been renumbered to affiliations 2 and 3 in the corrected manuscript.The Corresponding Author address for Mark Schure has also been corrected from:Mark Schure, BSc, MSc, PhDDepartment of Mechanical & Industrial EngineeringMontana State UniversityBozeman, MTUnited Statesto:Mark Schure, BSc, MSc, PhDDepartment of Health & Human DevelopmentMontana State University305 Herrick HallBozeman, MT, 59717United StatesThe correction will appear in the online version of the paper on the JMIR Publications website on October 23, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "In this paper, we consider the trust degree of a jammer, defined as the probability that the jammer cooperates to secure the legitimate transmission, and investigate its influence on confidential cooperative communication. According to the trust degree, we derive the closed-form optimal transmit signal-to-noise ratio (SNR) of the confidential message, With the rapid growth of communications between socially-connected users, not only physical parameters, e.g., channel qualities and traffic demands, but also the social relationship among users, such as kinship, friendship, and acquaintance, have been taken into account as key design parameters for efficient cooperative communications ,2,3,4,5.In the literature, the trust degree has triggered plenty of research interest in various fields, including content caching, mobile social communications, and especially cooperative communications ,2,3,4,5.Due to the broadcasting nature of wireless mediums, physical (PHY)-layer security has also drawn significant attention in communication networks ,9,10,11.Motivated by the aforementioned research and problems, we have observed that the trust degree plays a significant role in cooperative secure communications. Hence, in this paper, we consider the probability that the jammer cooperates in secure legitimate transmission as its trust degree and investigate its influence on the performance of confidential cooperative communications. Different from , we not Notation: For a complex scalar x, its complex conjugate is denoted by With the rapid growth of online social networks, more and more people are getting involved in online social interactions. Therefore, the social relationship has emerged as an important issue to investigate how the degree of closeness of the social relationship between users affects their communication strategies ,16,17,18In the literature, the trust degree has been evaluated and quantified in various ways ,21,22,23Consider a user cooperation network as shown in In this paper, we consider that Direct transmission: (a) Cooperative transmission: (b) According to the above strategies, the expected secrecy rate with respect to (w.r.t.) trust degree given in , is obta used in ,24. Notiiven in [R\u00afse (In In shown in , which hIn this paper, we investigated the confidential cooperative communication according to the jammer\u2019s trust degree and exploited its characteristics to design efficient cooperative strategies. To maximize the expected secrecy rate, we derived the closed-form optimal transmit SNR of the confidential message based on the trust degree and observed that the expected secrecy rate will become saturated along with the increasing"} +{"text": "The segetal flora of winter crops includes mostly native or archaeophyte annual species that are often strong specialists of their habitats. Threatened by the intensification of agriculture, segetal flora is particularly valuable from a perspective of biodiversity conservation and evolution. Moreover, it contributes to maintain biodiversity in agroecosystems and provides several ecosystem services. The dataset here described was set up to provide the first inventory of the segetal flora of Italian winter cereal crops and allied crop types, the latter including flax and autumn-sown legumes. It includes 24,676 georeferenced occurrence data deriving from 1,240 floristic and phytosociological relev\u00e9s. The data were collected from the greater part of Italian territory, in a temporal range spanning from 1946 to 2018. The concept of \u201cweed\u201d is very subjective, as any plant that interferes with human activities can be considered as such, implying the existence of agricultural weeds, environmental weeds, ruderal weeds and many others. Weeds of arable land are almost exclusively annual and are called \u201cagrestals\u201d or \u201csegetals\u201d . For decThe here presented dataset is available in GBIF and inclIn the light of what is stated above, the main aims of the present paper are the description and presentation of this recently-released dataset, providing information on its usefulness and possible future applications.Plant biodiversity in traditional agroecosystems of Italy: a floristic and ecological multi-scale analysis based on geodatabases.RM118164361D0EE4 .Giovanna Abbate, Mauro Iberite, Marta Latini, Emanuele FanfarilloSapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.The disappearance of traditional agroecosystems and the consequent biodiversity loss due to changes in agriculture are receiving increasing attention in Europe. The use of databases on plant taxonomical, distributional, ecological and functional traits is of crucial importance in conservation actions. The need to improve monitoring and reporting activities by improving the quality of biodiversity data is also underlined by the European Biodiversity Strategy. This project aimed at fulfilling a global analysis of the plant diversity existing in the traditional agroecosystems of Italy, knowledge of which is currently lacking, by means of the collection, digitisation and processing of original and archival data. The proposed actions concerned: the preparation of thematic databases on segetal flora and vegetation, including the features of plant species and communities; the analysis of data at different spatial and temporal scales; the production of thematic maps on plant diversity and its related topics; the development of new methods to estimate the nature value of agroecosystems; the detection of bio-indicator plant species for floristic richness, agricultural intensity and environmental quality. Special attention was given to winter arable plants and communities, currently at high risk of disappearance in Europe. The achieved results provided an important basis for any future research, with special regards to the definition of conservation strategies for plant diversity in European rural areas.The occurrence data were retrieved through extensive literature searches and intensive field samplings, the latter being carried out in the greater part of Italy to fill the knowledge gaps in some geographic areas. Literature data were selected using a habitat-based criterion: only the records for taxa unambiguously reported to grow in winter cereals, flax and autumn-sown legumes were collected. Consequently, all the records with no or with generic information on the growing habitat (e.g. \u201cfields\u201d or \u201ccultivated land\u201d) were excluded. Likewise, records of taxa identified to the genus or higher level, doubtful identifications, nomenclatural ambiguities and crop species were not considered. The bibliographic source of each record is available upon request to the authors.All the occurrence data were georeferenced. Geographic coordinates , geodetic datum and a value of uncertainty for coordinates were attributed to each single record. The geographic coordinates were manually attributed, based on the descriptions of the relev\u00e9 location provided in the original source. If coordinates were already available, they were converted in WGS84 geodetic datum, when differently expressed. The uncertainty of geographic positions was estimated according to the 9-degree scale defined by The taxonomic nomenclature was updated according to the latest standards available for the Italian flora and was published using GBIF Integrated Publishing Toolkit (IPT) publishing platform (https://cloud.gbif.org/eca). Once the data were imported in GBIF, the nomenclature was automatically referred to the GBIF Backbone Taxonomy 4.0 LicenseMetadata language: EnglishDate of metadata creation: 09-04-2020Hierarchy level: DatasetThe fields provided by the \u201cSegetal flora of Italy\u201d dataset are:occurrenceID, basisOfRecord, eventDate, scientificName, kingdom, taxonRank, decimalLatitude, decimalLongitude, geodeticDatum, coordinateUncertaintyInMetres, continent, country, countryCode, stateProvince, organismQuantity, organismQuantityType.Magnoliopsida , followed by Liliopsida and Polypodiopsida . Though, on the basis of the most recent results summarised by the APG , Ranunculales (12%), Caryophyllales (11%) and Fabales (8%). Poales (14%) is the most represented order within Liliopsida. The records in the dataset belong to 53 families, 340 genera and 859 taxa. The five most represented families, genera and species are shown in Tables Within sterales 5%, RanunKingdom: PlantaePhylum: TracheophytaClass: Magnoliopsida, Liliopsida, Polypodiopsida.Order: Alismatales, Apiales, Asparagales, Asterales, Boraginales, Brassicales, Caryophyllales, Cucurbitales, Dipsacales, Equisetales, Ericales, Fabales, Gentianales, Geraniales, Lamiales, Liliales, Malpighiales, Malvales, Myrtales, Oxalidales, Piperales, Poales, Polypodiales, Ranunculales, Rosales, Salviniales, Santalales, Saxifragales, Solanales.Family: Amaranthaceae, Amaryllidaceae, Apiaceae, Araceae, Aristolochiaceae, Asparagaceae, Asteraceae, Boraginaceae, Brassicaceae, Campanulaceae, Caprifoliaceae, Caryophyllaceae, Convolvulaceae, Cucurbitaceae, Cyperaceae, Dennstaedtiaceae, Elatinaceae, Equisetaceae, Euphorbiaceae, Fabaceae, Gentianaceae, Geraniaceae, Heliotropiaceae, Hypericaceae, Iridaceae, Juncaceae, Lamiaceae, Liliaceae, Linaceae, Lythraceae, Malvaceae, Marsileaceae, Onagraceae, Orobanchaceae, Oxalidaceae, Papaveraceae, Plantaginaceae, Poaceae, Polygonaceae, Portulacaceae, Primulaceae, Ranunculaceae, Resedaceae, Rosaceae, Rubiaceae, Santalaceae, Saxifragaceae, Scrophulariaceae, Solanaceae, Thymelaeaceae, Urticaceae, Verbenaceae, Violaceae.35\u00b023'60\"N, 6\u00b030'0\"E; 47\u00b012'0\"N, 18\u00b036'0\"E). Regarding administrative regions, the highest numbers of records are from Sicily, Veneto, Lombardy and Latium (Table The species occurrences stored in the dataset were recorded from the greater part of the Italian territory (Fig. The dataset includes species occurrences recorded from 1946 to 2018 (Fig. As expected, a high seasonality characterises the dataset. Most of the occurrences were recorded in spring and early summer. The months of greatest occurrence of the investigated taxa are, respectively, June, May, July and April Fig. .The \u201cSegetal flora of Italy\u201d dataset was the basis for the definition of the first inventory of the segetal flora of Italian winter cereal crops and allied crop types . The lat"} +{"text": "State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.\u201d Regarding to the numbering of the affiliations, the affiliation of Botany Department, Faculty of Science, Tanta University, Tanta, Egypt, instead of having affiliation #2, it should have the affiliation #3. For author Weimin Zhang, the affiliation should be \u201cState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China\u201d instead of \u201cBotany Department, Faculty of Science, Tanta University, Tanta, Egypt.\u201d For author Daochen Zhu, the second affiliation should be \u201cState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China\u201d instead of Botany Department, Faculty of Science, Tanta University, Tanta, Egypt. Regarding to the numbering of the affiliations, the affiliation of the State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China, instead of having affiliation #3, it should have the affiliation #2.In the published article, there were errors in affiliations of the authors Sameh S. Ali, Weimin Zhang and Daochen Zhu. For author Sameh S. Ali, the second affiliation should be \u201cBotany Department, Faculty of Science, Tanta University, Tanta, Egypt\u201d instead of \u201cAlso, in the article's citation, an author name was incorrectly presented as Morales GM. The correct spelling is Murillo Morales G.Figure 5, Additionally, Figures 1\u20135 were presented in a wrong order. E.coli BL21 (Laccase). Instead, it should be written as E.coli BL21 (Lacc). A correction has been made to abstract, last sentence:There was also an error in the abstract text. The name of the mutant bacterial strain was incorrectly written as E.coli BL21 (Lacc), under different initial pH conditions, demonstrated a promising potential to enlarge the spectrum of renewable products for biorefinery activities.\u201d\u201cLignin biodegradation products from The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer\u2019s disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition of AChE, its reactivation, and aging are discussed, along with a relationship to the current international legislation on chemical weapons. Over time, the use of incendiaries, darts, spears, and arrows impregnated with poisons from different organisms, animals, and plants, the lethality of substances used for warfare have been dramatically improved. Despite international agreements already in existence by the end of 19th century, these did not inhibit the large-scale use of CW during World War I (WWI) (1914\u20131918), when millions of casualties were provoked mainly by phosgene, chlorine, and, particularly, sulfur mustard (HD 1) . This co2 (GB), soman 3 (GD), and tabun 4 (GA) . These findings resulted in the weaponization of the first nerve agents, called also G-agents, which included sarin n 4 (GA) . Such CW5 and 6, 1, these compounds can be similarly regarded as \u201carea denial weapons\u201d [Later, during the 1950s, aiming to produce more effective pesticides, groups in the former Soviet Union, Great Britain, Sweden, and the United States developed other organophosphorus compounds which were more toxic and persistent (less volatile) than G-agents. These new chemicals were then named V-agents, which are phosphonothioates 5 and 6, [4,12,13weapons\u201d .2 and GA 4, along with sulfur mustard HD 1, against civilian and military targets during the Iran\u2013Iraq war. The tragic events in the Kurdish city of Halabja show how abhorrent can be the use of these substances as warfare agents [2 was employed in the terrorist actions carried out by the sect Aum Shinrikyo, provoking casualties among civilians and first responders [Although they were not used in the World Wars, the international community could soon testify their potential as Weapons of Mass Destruction (WMD) when, in the 1980s, Saddam Hussein\u2019s troops used chemical artillery containing G-agents, GB e agents ,17,18. Isponders ,21,22.Although many papers have dealt with chemical warfare over the years, the use of CW is currently a pressing subject. Recently, chemical warfare agents have made headlines due to their alleged deployment in the Civil War ongoing in Syria (2011\u2013) and as means of murdering the North Korean national Kim Jun Nam at the Kuala Lumpur International Airport in 2017. A report from Malaysian authorities confirmed that VX was used by the perpetrators ,40,41,427\u201310) [In 2018, events that occurred in Salisbury and Amesbury, Great Britain, where a former Russian agent and other people were poisoned with an \u201cunknown, high-purity grade military agent\u201d with possible neurotoxic effects, prompted discussions about the so-called \u201cNovichok\u201d agents. These then elusive compounds are predicted to act similarly to known nerve agents, but with higher toxicity and different physicochemical properties, for example, being solid at room temperature. After discussions on the actual structures of the Novichok agents, the most important agreement on chemical disarmament, the Chemical Weapons Convention (CWC), has acknowledged four novel scaffolds in its \u201cAnnex on Chemicals\u201d, which are to be entered into force in June 2020. 7\u201310) ,48,49,50From pharmacological and toxicological points of view, the biological targets of classical (G- and V-) and \u201cNovichok\u201d nerve agents are the cholinesterases, a class of enzymes involved in a myriad of biological processes, such as respiration, cognition, and drug metabolism. Cholinesterases are found in two isoforms, AChE (EC 3.1.1.7) and butyrylcholinesterase (BChE), EC 3.1.1.8. Compounds that can inhibit cholinesterases may impact the body positively or negatively and, therefore, be either explored as method of warfare or therapeutically ,65,66,67Herein, we review the inhibition of cholinesterases and their outcome and how these chemical reactions can be subject of interest in the treatment of neurodegenerative diseases, like Alzheimer\u2019s disease (AD) or as method of warfare, which is forbidden by the CWC.After many international agreements have sought to forbid the use of toxic chemicals as a mode of warfare, the Chemical Weapons Convention (CWC) entered into force in 1997, paving the way for the creation of the Organization for the Prohibition of Chemical Weapons (OPCW), the international watchdog responsible for overseeing the implementation of the CWC. The headquarters are located in The Hague, The Netherlands. As of January 2020, there are 193 signatories or State Parties to the CWC. In accordance to OPCW website, \u201c98% of the global population lives under the protection of the Convention\u201d and \u201c97% of the chemical weapons stockpiles declared by possessor States have been verifiably destroyed\u201d ,68, the In the preamble of the CWC, the State Parties are called out to ensure \u201cthat the complete and effective prohibition of the development, production, acquisition, stockpiling, retention, transfer and use of chemical weapons, and their destruction, represent a necessary step towards the achievement of these common objectives\u201d ,2,3.The current text of CWC has the \u201cAnnex on Chemicals\u201d section. There, compounds considered as chemical warfare agents or precursors are listed, along with the toxins saxitoxin and ricin. Chemicals are divided in Schedules 1 to 3), accordingly to the possibility of peaceful application to 3, ac. Schedul11 and chlorosoman 12, precursors to GB 2 and GD 3, respectively , a toxic chemical related to VX (5) is an example of Schedule 2A chemical. Diethyl methylphosphonate , is an example of Schedule 2B chemical, as it can be precursor for toxic nerve agents, but also flame-retardant materials , a15 and triethyl phosphite 16 . DEMP may be then chlorinated using thionyl chloride 18, a Schedule 3B chemical, yielding methylphosphonyl dichloride , another Schedule 2B chemical. MPDC is then reacted with a source of fluoride, generating methylphosphonyl difluoride , also a Schedule 2B chemical. Reaction of MPDF with isopropanol 21 in presence of a base, affords the toxic Schedule 1 chemical. There is comprehensive literature on the synthesis of organophosphorus compounds and researchers must read carefully the CWC, in the OPCW website (www.opcw.org) to learn more on the international legislation [Although synthetic relationships are not the criteria for the Schedule Chemicals, islation ,71,72,73Chemistry is ubiquitous, its principles and applications underlie innumerous biological processes, as is the case with cholinesterases, key enzymes in the metabolism of different species. This class of enzyme in superior animals is present in two different isoforms, as aforementioned, AChE and BChE. AChE is involved in the regulation of neurotransmission processes (parasympathetic neurotransmission), being important for (but not limited to) cognition and respiration, for example. BChE is found in plasma, being responsible for hydrolysis of different esters, property that has been studied to understand a series of metabolic events or for treatment of cocaine addiction, for example. Furthermore, it has been extensively studied due to its stoichiometric reaction with organophosphorus compounds, which indicates that it is not only a biomarker of exposure to these toxic chemicals but also a potential treatment for intoxication, acting as bioscavenger of nerve agents ,81,82,8322 and aldicarb 23 , into acetate 26 and choline 27 through a tetrahedral transition state 28 at the post-synaptic cleft, ending the action potential, in accordance with the proposal below during ACh hydrolysis. Finally, the acyl pocket site (APS) is the point where the difference between AChE and BChE may be assessed, with AChE having a smaller APS than BChE, determining the size of the substrate to be hydrolyzed [A schematic representation of different sites of AChE is shown in drolyzed ,91,92,9325, the parasympathetic neurotransmitter, into choline 26 and acetate 27, which are reuptaken for de novo synthesis of the neurotransmitter. Therefore, AChE is a pharmaceutical target, as its inhibition provokes an increase of neurotransmitter concentration at the post-synaptic cleft, leading to exacerbated cholinergic response over the nerve structures that require parasympathetic stimulation, such as neuromuscular junctions. This outcome may be positive, as in the case of treatment of diseases where the transitory, reversible inhibition of AChE located in the central nervous system (CNS) delivers valuable response, e.g., AD, or negative, when toxic chemicals, such as nerve agents or other suitable entity , an alcohol 31 is displaced , donepezil , and galantamine . The fourth compound is memantine , which affects other receptors [Currently, there are only four drugs available to ameliorate the memory loss and other symptoms related to AD. Nonetheless, they can only act in a certain level of impairment and are unable to halt the progression of the pathology. Consequently, knowledge on the different mechanisms that can contribute to the onset of AD and discover of the early neurological, biochemical, and behavioral changes, useful for the development of a more efficient treatments. Three of these compounds act as AChE inhibitors, rivastigmine ,126,127.4 receptor inhibitors and PROTAC (PROteolysis Targeting Chimeras) compounds, among other approaches [Rivastigmine is regarded to react with the serine residue of the ES present in AChE and BChE which illustrates the clinical effects. Acute exposure may be fatal due to the respiratory failure resulting from the continuous stimulation of neuromuscular junctions at diaphragm, as described earlier in this paper [22 and aldicarb 23 that can be used as proof of exposure to nerve agents. Nevertheless, if the enzyme is not aged 44, treatment with fluoride ions enables a de novo synthesis of the organophosphorus compound 47. These compounds can be successfully detected by chromatographic and spectrometric techniques , an anticholinergic agent (to counteract the effects of the higher concentration of the neurotransmitter), and an anticonvulsant (to control seizures). Up to date, pyridinium oximes have been clinically used as AChE reactivators, pralidoxime ompounds [4,182,1erase 56 ,192,193.59 as anticholinergic agent, and an anticonvulsant, such as diazepam 60 hinders effective treatment. Additionally, an efficient \u201cuniversal antidote\u2019 towards all cholinesterase inhibitors is not yet available . To tackCholinesterases are constitutive enzymes, essential to the correct performance of the parasympathetic nervous system (PNS). The chemistry of AChE inhibition and aging in the context of the contemporary issue of terrorism by chemical warfare is an attractive conduit for chemical education and for dual use, military and civilian research work. AChE has a pivotal role in memory and learning, therefore increased knowledge on AChE function may facilitate the development of further, more effective therapies towards neurodegenerative diseases, like AD. Besides the varied conceptual background in Chemistry that it demands, the subject is also multidisciplinary, since it is related to pharmacology, toxicology, medicinal chemistry, international politics, health, environmental and forensics sciences, as well ethical issues."} +{"text": "Spinning, what you will, in heeding that swarm of guidance, creatingyour own shell, then transforming, as you will, within that isolation,still seems like an almost unconvincing, almost unnecessary nuisance.You had chosen this situation, if it is fair to say there was a choice,when there was no viable alternative. Your cocoon can feel so safe,an illusion perhaps, but reality provides nothing less vulnerable.The walls are thin enough to allow you to breathe, and to vaguely hearor feel vibrations, even though their meaning cannot be known.Light penetrates, and darkness, too; the changes remain obscure.Ruminating on that former lifestyle, you can digest time thoroughly,like those last memorable green leaves of Springtime, then so succulent,and satisfying, but to what end you know not; not all cocoons survive.Time, space, being, identity, the interpreted past, the fancied futurecan all be consumed within your insatiable capsule. Chrysalis or cocoon,distinctions no longer matter; each benefits from a covering and distancing.Complacency or contentment allows a concentration on one\u2019s onlycertainty, the presentness right now, in this cell-like confinement,because emergence would require several just preposterous miracles."} +{"text": "In the published article, there was an error regarding the affiliations for R. de Diego-Balaguer. As well as having affiliation 3, she should also have:4 Catalan Institute for Research and Advance Studies, Barcelona, Spain5 Cognition and Brain Plasticity Unit, IDIBELL, L'Hospitalet de Llobregat, Spain6 Institute of Neuroscience, University of Barcelona, Barcelona, SpainThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Objective assessments of movement impairment are needed to support clinical trials and facilitate diagnosis. The objective of the current study was to determine if a rapid web\u2010based computer mouse test (Hevelius) could detect and accurately measure ataxia and parkinsonism.Ninety\u2010five ataxia, 46 parkinsonism, and 29 control participants and 229,017 online participants completed Hevelius. We trained machine\u2010learning models on age\u2010normalized Hevelius features to (1) measure severity and disease progression and (2) distinguish phenotypes from controls and from each other.r =\u20090.66 for UPDRS dominant arm total to r =\u20090.83 for the Brief Ataxia Rating Scale). A disease change model identified ataxia progression with high sensitivity. Classification models distinguished ataxia or parkinsonism from healthy controls with high sensitivity (\u22650.91) and specificity (\u22650.90).Regression model estimates correlated strongly with clinical scores (from Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.Hevelius produces a granular and accurate motor assessment in a few minutes of mouse use and may be useful as an outcome measure and screening tool. \u00a9 2019 The Authors. Drug development efforts are underway for patients suffering from neurodegenerative diseases, including cerebellar ataxias, Parkinson's disease (PD), and Parkinson\u2010plus syndromes. Key challenges for clinical trials include the ability to accurately diagnose early diseaseSuch challenges are amplified in children in whom norms for movement evolve rapidly with age. Furthermore, disease\u2010tailored clinical scoring scales are limited in their ability to measure nonprototypical phenotypes, for example, in ataxia patients with bradykinesia. Because of the complex, heterogeneous, and overlapping phenotypes in neurodegenerative diseases, it would be advantageous to complement existing assessment methods with a readily available tool that could characterize movement across a number of phenotypes.We have developed a rapid, computer mouse\u2013based tool called Hevelius that quantifies arm function by extracting 32 features from continuous, target\u2010driven computer mouse trajectories . Here, we demonstrate the effectiveness of Hevelius (1) to accurately measure disease severity and (2) to distinguish patients with ataxia or parkinsonism from controls and from each other.Data from 229,017 online participants were used to develop the normative data set. Participants self\u2010reported coming from 158 countries, with the largest group coming from the United States (43.8%).1,185 = 19.99, P\u2009<\u20090.0001).One hundred and eighty\u2010nine patients were assessed using Hevelius in the clinic setting: 95 with cerebellar ataxia, 46 with parkinsonism, and 29 controls were increased, and those related to movement control were impaired compared with online controls in both ataxia and parkinsonism total and common total score. The mean absolute error (MAE) for all was <10% of the maximum score. The MAE for Hevelius \u00b1 standard deviation (SD) in estimating BARS dominant arm score was 0.35\u2009\u00b1\u20090.30, comparable to the previously published MAE of 0.38 of expert clinicians asked to rate video recordings of the finger\u2010nose\u2010finger task.The estimates produced by the regression models correlated strongly with actual clinical scores. The correlation coefficient ranged from r = 0.89, P\u2009<\u20090.0001; UPDRS, r = 0.82, P\u2009<\u20090.0001; common score, r = 0.85, P\u2009<\u20090.0001).Although Hevelius measures dominant arm performance, it is equally effective for predicting dominant arm score and total score. This is not surprising given that in our data set dominant arm score and total score were highly correlated and healthy controls with high sensitivity (\u22650.91) and specificity (\u22650.90); see Table A model trained to discriminate between healthy controls and early\u2010stage ataxia patients (BARS score of 0 in the dominant arm), yielded a sensitivity of 0.75 and specificity of 0.97.A binary classification model trained to learn which session in a pair of sessions was more severe was applied to 18 individuals with a progressive ataxia diagnosis and a repeat session . The mean interval duration between sessions was 325\u2009days with a range of 126\u2013469\u2009days. In these 18 individuals, the dominant arm BARS score increased (indicating disease progression) in 8 of 18, was unchanged in 9 of 18, and decreased (indicating improvement) in 1 of 18 . The classification model predicted that 17 of 18 individuals had increased dominant arm severity at the time of their second session. One of 18 was predicted by the model to have decreased severity on the second session . These results support that Hevelius can sensitively capture arm severity progression information.Hevelius is a novel tool for performing objective, granular, and rapid assessments of dominant arm motor function. We have demonstrated that the tool can be used in children and adults and forms an interpretable and multidimensional representation of ataxia and parkinsonism.We have shown that the 32 movement features computed from computer mouse trajectories are interpretable, capture several dimensions of motor control, and vary with development and aging . Despite age adjustment enabled by the normative data set, it is conceivable that not all age\u2010related factors were fully removed, resulting in inflated performance estimates of classification models.Krzysztof Z. Gajos, PhD, Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA: conception, organization, execution of the research project; design, execution, and review and critique of the statistical analysis; 3. writing of the first draft and review and critique of the manuscript. Katharina Reinecke, PhD, Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA: execution of research project; review and critique of manuscript. Mary Donovan, BS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA: execution of the research project. Christopher D. Stephen, MB, ChB, Ataxia and Movement Disorders Units, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA: execution of the research project; review and critique of the manuscript. Albert Y. Hung, MD, PhD, Movement Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA: execution of the research project; review and critique of the manuscript. Jeremy D. Schmahmann, MD, Ataxia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA: execution of the research project; 3. review and critique of the manuscript. Anoopum S. Gupta, MD, PhD, Ataxia and Movement Disorders Units, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA:. conception, organization, and execution of the research project; review and critique of the statistical analysis; writing of the first draft and review and critique of the manuscript.Krzysztof Z. Gajos, PhD, is employed by Harvard University and has received grants from NIH, NSF, and Adobe. Katharina Reinecke, PhD, is employed by the University of Washington, has received grants from NSF CAREER Grant, and gift money from Adobe Research, Microsoft, and Google CSO of Startup Augury Design Inc. Mary Donovan, BS, is employed by Massachusetts General Hospital and is a medical student at Georgetown University. Christopher D. Stephen, MB, ChB, is employ8ed by Massachusetts General Hospital, has received grants from Sanofi\u2010Genzyme, has receceived compensation for conducting clinical trials from Sanofi\u2010Genzyme, Bristol\u2010Myers Squibb, Biogen Inc., and Biohaven Pharmaceuticals Inc. Albert Y. Hung, MD, PhD, is employed by Massachusetts General Hospital. Jeremy D. Schmahmann, MD, has stock ownership Cadent Pharmaceuticals, intellectual property rights in the Brief Ataxia Rating Scale, Cerebellar Cognitive Affective Syndrome Scale, and Cerebellar Neuropsychiatric Rating Scale and is a license holder with the General Hospital Corporation, is a consultant for Cadent and Biohaven, has given expert testimony for the Massachusetts Committee for Public Counsel Services. is on advisory boards of Cadent, National Ataxia Foundation, Society for Research on Cerebellum and Ataxias, is employed by Massachusetts General Hospital, has received honoraria from the Institute of Neurology Queen Square, British Neuropsychiatric Association, Spanish Neurological Society, New York University Langone Medical Center, American Speech\u2010Language\u2010Hearing Association, Department of Neurology Emory University, Montefiore Medical Center and Albert Einstein School of Medicine, has received royalties from Oxford University Press, Elsevier, Springer, MacKeith Press, has received grants from National Ataxia Foundation, NIH, US Army Medical Research, and has received compensation for conducting clinical trials and sponsored research from Biohaven Pharmaceuticals Inc. Anoopum S. Gupta, MD, PhD, was a consultant for Biogen, Inc., is employed by Massachusetts General Hospital, has received grants from Ataxia\u2010Telangiectasia Children's Project, Biogen, Inc.Appendix S1: Supplementary MethodsClick here for additional data file."} +{"text": "Scientific Reports 10.1038/s41598-020-60897-4, published online 06 March 2020Correction to: In the HTML and PDF of the original version of this Article Hye Seung Lee was incorrectly affiliated with \u201cDepartment of Laboratory Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea\u201d The correct affiliations for Hye Seung Lee are listed below.Department of Pathology, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.Department of Pathology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.Additionally, the Supplementary Figure S1 file contained errors in the affiliation list where affiliations 2, 4 and 6 were omitted. As a result, affiliation 3 was listed as affiliation 2, affiliation 5 was listed as affiliation 3 and affiliation 7 was listed as affiliation 4.These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "In the original publication of this article, the author Serghei Mangul was erroneously listed with a second affiliation: Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, 90\u00a0090, USA, which has been removed from the author byline. The authors regret this error."} +{"text": "Background: Dementia, a significant cognitive impairment, is characterized by a decline in memory. It affects an individual\u2019s mood and behavior, which can impair their quality of life and well-being. Studies show that the demand for applying music as a new therapy method for dementia has increased during the last decades. Objective: To review the studies conducted on the impacts of music on different symptoms of dementia and provide readers with a more detailed picture of the efficacy of music, and recognize gaps in the literature. Methods: Electronic searches were conducted in the Cochrane Library (1938), Embase (773), Medline and PubMed (700), PsycINFO (89), and Scopus (218) databases. The search was comprised of all the literature from 2010 to 2020. For the search, key terms including \u201cDementia\u201d AND \u201cmusic\u201d OR \u201cmusic intervention\u201d OR \u201cmusic therapy\u201d and index terms \u201cclinical trial\u201d OR \u201crandomized controlled trials\u201d were used. Finally, after screening 891 citations, 30 studies were included. Results: In general, it was observed that in most cases, music could be used as one of the safe and cost-effective non-pharmacological approaches for dementia treatment. However, in some studies, no impact or short-term effect of music on some symptoms of dementia such as wandering, agitation, and cognition was detected. Conclusion: Observing no effect or even negative impact of music on people living with dementia could be due to a random selection of music, fewer individuals, and the lack of a standard protocol. High heterogeneity in outcomes did not allow for clear conclusions on the benefits of music in dementia. This demands a comprehensive non-pharmacological music treatment approach to be designed for each stage of dementia to be employed alongside pharmacological treatments. This study proposes 13 gaps in the research on the health impact of music on dementia that could be studied by future researchers. Dementia is an umbrella term for several progressive diseases such as Alzheimer\u2019s that affect memory, language, problem-solving, and the individual\u2019s thinking ability, which interfere with their daily living activities . People There are various kinds of therapy methods for managing dementia symptoms: pharmacological and non-pharmacological. Although evidence shows that pharmacological therapy can delay and somewhat control behavioral disorders in PWD, it cannot cure dementia . Some poSeveral physiological and psychosomatic benefits of music have been mentioned in the literature.Biological/physiological: The physiological effect of music helps to balance vital signs such as blood pressure, heart rate, respiratory rate, and hormone levels [e levels ,18.Behavioral and psychological: The psychological effects of music help to reduce mood fluctuations and behavioral disorders such as depression, agitation, and aggression [gression ,19,20,21Cognitive: Music also boosts communication skills, the quality of life, well-being, intimacy, memory, self and environmental awareness, the ability to distinguish between the surroundings and moments of the day, and managing pain [ing pain ,22,23. Aing pain ,24. PWD Emotional: Music engages the individual\u2019s attention (apathy) and helps them enjoy their life, improves their self-esteem, and communication, which leads to improvement in behavior [behavior . People behavior .To retain the music benefits, people with dementia need to receive regular music treatment, which is approximately two to three times a week . OverallMusic intervention can be performed at home or in residential aged care facilities, as individual or groupSpecific symptoms of dementia such as depression ,20,36,37Group music therapy ;Specific stage or type of dementia ,41,46; Recorded music ;Music and exercise ;Assessment tools for measuring music\u2019s impact ;Residents living in a residential aged care facility ; andIndividualized music .Previous review studies have limited their focus to the following aspects: The main aim of this review was to investigate music\u2019s efficacy on people living with dementia by exploring the changes in the different symptoms of dementia including a broader setting. We also provide readers with a more detailed picture of the music\u2019s efficacy by analyzing the gaps in previous studies and suggesting more appropriate research design and methodological considerations that need to be addressed in future studies.Intervention typeThe focus of the studyExperiment designTherapy approachIntervention settingEvaluation scales and results The objective of this meta-narrative review was to investigate the publications using a qualitative approach and systematic review by highlighting the contrasts and similarity on music\u2019s efficacy. Electronic searches in the Cochrane Library (1938), Embase (773), Medline and PubMed (700), PsycINFO (89), and Scopus (218) databases were performed to find all of the peer-reviewed publications in English that had the keywords and search terms \u201cDementia\u201d, \u201cmusic\u201d, \u201cmusic intervention\u201d, \u201cmusic therapy\u201d, \u201cclinical trial\u201d, and \u201crandomized controlled trials\u201d in their titles and abstracts. The time frame chosen for this search was from 2010 to 2020. In general, studies that fit in all of the following criteria were included in this review:Papers that did not have any details about one of the criteria as above-mentioned have not been included in this review. Additional articles were identified through a review of reference lists of included articles, titles, and abstracts. Identified citations were exported into Mendeley, and duplicates were removed.Among the 891 studies, only 30 met the inclusion criteria and were selected for further investigation .We extracted data on the study areas, type of dementia, intervention design, number of participants, study environment, conductor of the study, measurement scales, and results. The measurement and results are summarized in the Previous studies have identified some areas that need to be covered to draw clear conclusions on music\u2019s efficacy for PWD. Some of the suggested areas such as combining MT with other activities ,47,49, dControl group: To compare individuals living with dementia who experience music treatment and others who only receive pharmacological treatment or are involved in other activities, it is necessary to divide people with dementia into two groups: a control group or a study group. Although sixteen papers out of 30 [ut of 30 ,58,59,60ut of 30 ,67,68,69ut of 30 ,55 with Gender: Although researchers have included different genders in their study, only one of the studies identified music\u2019s impact based on gender [n gender . In thisSample size: The sample size of the studies varied from eight to 165 participants. In several studies, the sample size of the experiment was less than ten [than ten ,58,61,70than ten , where ethan ten ,69 incluLong-term effect: Some studies have found that music had a short-term impact, but it is unclear if music can be beneficial in the long-term. Only two studies reported long-term [ong-term ,34, one ong-term , and oneong-term . In one ong-term , residenong-term . As a reLive or recorded music: Music intervention sessions are conducted either as a recorded [recorded ,66,67,69recorded based onrecorded ,59,61,65recorded selectedrecorded ,26, recorecorded ,51,58,68recorded ,70 selecrecorded ,63,67,70recorded ,52,54,65Music intervention or music therapy: Researchers have sometimes mixed the definition of music intervention (music medicine) with music therapy and considered any types of music treatment as music therapy. Among the 30 reviewed studies, only nine of them considered music therapy [ therapy ,64,68,70 therapy ,68,70 or therapy ,34 modes therapy ,64. Musi therapy ,57,59,67 therapy ,64,65,69 therapy ,50. Alth therapy . While m therapy ,50, reseSelecting appropriate music and professional therapists: The music treatment approach aims to decrease the costs, and it is not obvious that it is necessary to hire professional music therapists to conduct music sessions, or medical personnel can conduct the therapy session. While some researchers have tried to use PWD\u2019s favorite song [ite song ,56,62,64ite song ,58,61,63ite song ,64,70. TPhysiological impact: In addition to changes in psychological data, dementia may cause changes in physiological signals. One study [ne study found thne study ,71. In oLack of an exact measurement scale: Although most of the studies employed quantitative measurement mechanisms that used clinical scales, some researchers did not apply any particular measurement scale. Some researchers have monitored changes in PWD\u2019s moods and behavior by observing and analyzing their body or facial expressions [ressions ,57,65, oressions ,63,70. ICombination of music with pharmacological methods: One study [ne study pointed Combination of music with other activities: Although some studies have proved that listening to music and being involved with social activities positively impact dementia symptoms, only nine studies combined various activities such as playing games, solving word-puzzles, gardening, and engaging in mental or physical activities [tivities ,59,60,68tivities . Severaltivities . In anottivities , short-tImpact on agitation, wandering, and cognition: The impact of music treatment on the agitation, wandering, and cognition of individuals with moderate or severe dementia is not completely clear. While seven out of 30 studies discussed a reduction in agitation [gitation ,55,57,65gitation . Anothergitation did not Benefits of music for family members and caregivers: In one study, it was mentioned that music therapy could also increase caregivers\u2019 satisfaction [sfaction . The impThis meta-narrative review on the previous studies indicated some improvement in the physiological or psychosomatic behaviors of people living with dementia after music intervention ,57,67,70Overall, these studies have focused on the short-term impacts of music on people with dementia. One of the drawbacks with the previous studies is using the terms incorrectly in the literature and referring to any type of musical intervention as a music therapy. Thus, it is important to distinguish between using music intervention and music therapy. Music intervention or therapy has mixed outcomes, which do not guarantee it as a long-term therapy solution. Therefore, to have more reliable results, high-quality longitudinal, cross-sectional studies should be conducted to identify the confounding factors. Additionally, a bigger sample size with both control and study groups is needed. Additionally, controlling for pharmacological therapy and other intervention methods could be beneficial for investigation into the impact of music in isolation and also in combination with other treatments. Additionally, researchers should examine whether recorded music can have the same outcome as live music, which would decrease the cost for hospitals and nursing facilities. Fewer studies on personalized music intervention ,54,57 deOne of the symptoms of dementia is changes in vital signs such as blood pressure, heart rate, and vitamin deficiency. This review found three papers that considered vital signs ,58,71 giAdditionally, only two papers considered the benefits of music for family members and caregivers ,68, whicOverall, for future research, it is beneficial to consider all aspects of the methodological considerations discussed in this review including gender, control group, sample size, long-term effects, whether it is live or recorded, receptive or active music intervention or therapy, personalized or selected music by caregivers or music therapists. Furthermore, combining music treatment with other activities that involves both PWD and their family or caregivers may be beneficial, along with targeted pharmacological treatments."} +{"text": "Edible crickets are among the praised insects that are gaining recognition as human food and livestock feed with a potential of contributing to food security and reduction of malnutrition. Globally, the sustainable use of crickets as food or feed is undermined by lack of information on the number of the edible crickets, the country where they are consumed, and the developmental stages consumed. Furthermore, lack of data on their nutritional content and the potential risks to potential consumers limits their consumption or inclusion into other food sources. We reviewed published literature on edible cricket species, countries where they are consumed, and the stage at which they are consumed. We further reviewed information on their nutritional content, the safety of cricket consumption, and the sensory qualities of the edible crickets. We also looked at other benefits derived from the crickets, which include ethnomedicine, livestock feed, pest management strategies, contribution to economic development, and livelihood improvement, particularly in terms of use as food preservatives and use within music, sports, and cultural entomology. Lastly, we reviewed information on the farming of edible crickets. In this review, we report over 60 cricket species that are consumed in 49 countries globally. Nutritionally, crickets are reported to be rich in proteins, ranging from 55 to 73%, and lipids, which range from 4.30 to 33.44% of dry matter. The reported amount of polyunsaturated fatty acids (PUFA) is 58% of the total fatty acids. Edible crickets contain an appreciable amount of macro- and micro-mineral elements such as calcium, potassium, magnesium, phosphorus, sodium, iron, zinc, manganese, and copper. Also, the crickets are rich in the required amount of vitamins such as B group vitamins and vitamins A, C, D, E, and K. Overall, the cricket species examined in this review are safe to be consumed, and they display high proximate content that can replace plant and livestock products. The crickets play valuable roles in contributing to the economies of many countries and livelihoods, and they have medicinal and social benefits. This review is expected to promote greater recognition of crickets as a source of food, feed, and other benefits in the world and encourage up-scaling by farming them for sustainable utilization. Brachytrupes membranaceus , 38Brachus icipe .Jongema documentCrickets have been consumed as food in Asia, Latin America, and Africa as far back as prehistoric times. In Biblical scriptures, cricket consumption is recommended to the Israelites by God to be fit for their consumption: \u201cthese you may eat any kind of locust, katydid, cricket or grasshopper\u201d (Leviticus 11: 22). In China, crickets have been consumed as food for over 2,000 years , 39. In A. domesticus to be two-fold as compared to that of broiler chickens and pigs, four-fold compared to that of sheep, and more than 12-fold compared to that of cattle. Moreover, crickets may be produced on locally available food substrates such as agro byproducts and weeds, and they thus aid in cleaning the environment and polyunsaturated fatty acids (PUFA), mineral elements, carbohydrates, energy, and the ease of farming make crickets promising as a sustainable food source , 48. Theironment , 29, 51.ironment , 44, 45.ironment . House cWhile edible crickets are found to be rich sources of proteins and other nutrients , 53, theCrickets are non-wood wild products found in natural resources all around the globe apart from cooler regions at latitudes 55\u00b0 and beyond; the greatest species abundance is found in the tropics where temperatures are warm and suitable for their faster development compared to cold regions . CricketEdible crickets are excellent sources of proteins, lipids, carbohydrates, mineral salts, and vitamins . HoweverBrachytrupes sp. and 83.9% for A. domesticus per 100 g of dry weight . The enelt stage , 61 and arachidonic acid (50.43 g/100 g of dry matter) are the most abundant fatty acids in Brachytrupes sp. and B. portentosus, respectively , and palmitic acid (C16 fatty acid) as compared to other fatty acids , 73, 115ectively . The seccalities , 58, 114Tarbinskiellus portentosus, G. testaceus, G. assimilis, A. domesticus, A. confirmata, Brachytrupes sp., and B. portentosus have higher content of polyunsaturated fatty acids (PUFA) compared to pork and broiler chicken meat compared to pork and broiler chicken meat. Most of the crickets in our review, except for G. bimaculatus and T. emma, have more essential fatty acids than the pork and broiler chicken. Crickets generally have more unsaturated fatty acids (UFA) compared to saturated fatty acids (SFA) , and some cancers affecting human beings, are due to the consuming of SFA , 61. A nd to UFA . This dig of SFA . Consumpg of SFA .Gryllus bimaculatus cricket contains the highest amount while Brachytrupes sp. contains the least amount of calcium is applied to patients suffering from athlete's foot for treatment diet containing 100, 75, 50, 25, and 0% fish meal can be successfully changed to contain 0, 25, 50, 75, and 100% G. bimaculatus crickets, respectively . Gathering crickets from farms and consuming them as food can also help in reducing pesticide use in controlling these cricket pests. This, in return, can protect the environment from pollution, minimizing the killing of other useful insects and poisoning of consumers . This practice of allowing crickets to fight was later declared illegal during the Qing Dynasty (1644\u20131911 CE). Currently, however, cricket fighting is legal, and it has become a common sporting activity in many Chinese cities, such as Beijing, Guangzhou, Huwan, Hong Kong, Shanghai, and Tianjin, where cricket fighting clubs and societies have been formed . CricketCrickets have contributed a lot to the shaping of literature, art, and doctrine in societies around the world\u2014referred to as cultural entomology . ContribThe crickets have also played different roles in folklore and superstition in different parts of the globe. In this perspective, some communities hold a lot of esteem for crickets since they believe that once you hear the song of the cricket it spells good fortune, although others say it is a bad omen when a cricket makes noise around you. In China, for instance, the crickets have been implicated to foretell the coming of rain, death, or the returning of a lover who has been away . MoreoveScapteriscus and Neocurtilla, Gryllotalpidae) that enters into the house of a Brazilian brings both good luck and rainfall . The othA. domesticus and Brachytrupes. The results showed that various types of Enterobacteriaceae and sporulating bacteria can be identified and subsequently seperated from raw crickets entering them most likely during contact with the soil , the short-tail cricket B. portentosus, and T. portentosus , 189. Extentosus , 189\u2013191he globe .A. domesticus, G. bimaculatus. They, however, prefer rearing G. bimaculatus, which form a greater portion of the Thai production since G. bimaculatus has a short lifecycle and is stronger and hardy, though less popular than A, domestica , brown field cricket (G. assimilis), and two-spotted field cricket (G. bimaculatus) are the common crickets bred in Europe and for industrial processing . A grant from the Danish government facilitates the technology transfer of cricket farming through GREENiNSECT project that supports \u201cthe rearing and eating crickets as a delicious, affordable and healthy solution for malnutrition.\u201d The project has accelerated, leading to the establishment of small-scale cricket farms in L. Victoria region, which was the initial point of introduction in Kenya and Uganda. From this point of introduction, cricket farming has spread to other regions, such as central Kenya and the coast of Kenya. Three cricket species, S. icipe, A. domesticus, and G. bimaculatus are reared (Scapsipedus icipe and A. domesticus are most popular among farmers because they are softer than G. bimaculatus. In Kenya, there are about 300 cricket farmers who produce 28,800 kg of crickets per year (In Africa, cricket farming is at its infancy stage in countries such as Kenya, Uganda, Mali, and Madagascar , 202. Cre reared , 204. Inper year . The criper year , the larper year ,. The yiFarming of crickets requires varying degrees of labor input during the rearing cycle . Each daicipe have already assessed hygienic and toxicological and microbial risks related to edible crickets, more research on their composition and nutrient profile should be carried out to fully implement edible crickets as food into the global legislation documents. Currently, there are only a few cricket species that are farmed. The farmers must be encouraged to start rearing other species of crickets that have not yet been confined. Also, animal breeders should try to find out whether it is possible to crossbreed the crickets with a long lifecycle with the ones with a short lifecycle.The current study has shown that consuming crickets as food by human beings is traditionally practiced in 49 countries around the world. Over 60 cricket species are known to be edible. Crickets are a highly nutritious food resource and may therefore be included in the list of the common diet of global consumers in the future. These crickets could also be used as nutritional supplements for special diets for schoolchildren, sick people, and athletes. Inclusion of potentially suitable species of crickets into the normal diet requires defined and standardized conditions of their rearing as well as the detailed monitoring of their composition, including biologically active compounds. Though the EFSA and Edible crickets have become popular in the past few years not only in the scientific literature but in other platforms as well. One of the major advantages of eating crickets is their impressive nutritional composition. Many sources report that crickets have better nutritional characteristics than traditional protein sources. In our research, we aimed to give a complete picture of edible crickets in the world, their nutritional profile and other benefits. The materials we used are published results of different authors from the past few years. The list of crickets provided by various authors' shows that there are 66 crickets that are consumed as food and feed in the world and crickets generally have a better nutritional profile than other meats. Based on our findings, crickets have a promising nutritional profile in terms of energy, protein, lipids and important fatty acids, mineral elements vitamins, carbohydrate and medicinal elements and may become part of many food products in future. As an enterprise, cricket farming, can mitigate food insecurity, act as a source of income when sold and a source of employment. The present review provides comprehensive information on the diversity of crickets, their nutritional values and their potential to contribute to the livelihood of mankind.HM, SN, MA, MM, SE, JE, EK, JO, SH, KF, MO, NR, and CT: conceptualization, writing\u2014original draft, and writing\u2014review and editing. HM, SN, EK, and SH: data curation. HM, SN, EK, SE, and MM: formal analysis. HM, SN, MA, MM, SH, NR, SE, JE, EK, and KF: methodology. HM, SN, and EK: software. SN, MM, JE, SE, SH, CT, and KF: validation. HM: investigation. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Biosensors and micro-electromechanical systems (MEMS) have witnessed rapid development and enormous interest over the past decades. Constant advancements in diagnostic, medical, and chemical applications have been demonstrated with regard to several platforms and tools. Biosensors, relying on various sensing platforms such as surface plasmon resonance, piezoelectric, electrochemical, lab-on-a-chip, and paper, have been broadly used in research. Covering various excitation and readout schemes, MEMS devices transduce physical parameter changes, such as mass, temperature, or stress changes, caused by alterations in anticipated measurands, to electrical signals that can be further processed. Common examples of MEMS platforms include accelerometers, magnetic field sensors, pressure sensors, radiation sensors, microphones, and particulate matter sensors.In total, nine papers are published in this Special Issue, covering biosensors and MEMS-based diagnostics applications ,6,7,8,9.This Special Issue also covers three comprehensive reviews written by the research groups of K\u00fclah, Altintas, and Bui and Medintz, respectively ,8,9. ThiI would like to take this opportunity to thank all of the authors for submitting their papers to this Special Issue. I also want to thank all of the reviewers for dedicating their time and helping to improve the quality of the submitted papers."} +{"text": "To the Editor\u2014Coronavirus disease 2019 (COVID-19) is a respiratory tract infection ranging from mild respiratory illness to severe illness 1 that has caused an unprecedented global crises in <90 days in all 206 countries of the world.2 Today, most of the world\u2019s major cities are in full quarantine and all social and economic behaviors have been limited due to the SARS-Cov-2 outbreak. Controlling the spread of the virus has become one of the most important challenges for governments across the globe. The increase in COVID-19 cases in the advanced industrial countries, including Italy, Germany, France, Spain, and United States, reflects the rapid spread of the virus. As of April 4, 2020, the following countries have been most affected: Italy, with a populations of almost 60 million, has ~119,827 COVID-19 patients . Germany, with a population of almost 82 million, has ~85,778 COVID-19 patients . France, with a population of almost 66 million, has ~63,536 COVID-19 patients . Spain, with a population of almost 46 million, has ~117,710 patients . And the United States, with a population of 320 million, has ~241,703 patients . The prevalence of SARS-CoV-2 is rapidly increasing. Iran, with a population of almost 81 million, has ~44,605 COVID-19 patients, with 2,898 deaths (Fig.\u00a035 Iran formed a headquarters for the COVID-19 crisis on February 23, when the virus count was ~15 people per day. In contrast, in Italy, the COVID-19 crisis headquarters was formed on March 13, when the outbreak count was ~2,500 per day. Also, these countries\u2019 respective health ministries published safety and prevention guidelines for many locations, especially crowded centers including hospitals, clubs, transportation systems, schools, etc, in the early days of the outbreak. They also sought widespread collaboration with NGOs and volunteers as well as extensive intragovernmental collaboration to ensure the observation of safety protocols to control the spread of disease. Although traffic and concentration laws as well as heavy fines were not considered in the early days, these collaborations ultimately resulted in an 80% reduction in traffic between cities and as well as in social gatherings and even family gatherings. Ultimately, all of these measures have led Iran to better control the spread of the virus than other aforementioned industrialized countries. Nevertheless, Iran has a long way to go to achieve complete control of the pandemic.For example, Italy, with an outbreak date similar to that of Iran, has more than twice the disease incidence rate of Iran. According to reports released by the ministries of health in Iran and Italy,6 This experience and history are expected to be very useful and effective in controlling COVID-19.Because Iran is located among neighboring countries in a very high-risk area for many diseases, including tuberculosis, rabies, Crimean Congo fever, cholera, brucella, malaria, polio, and some others, it has been even more successful in controlling such diseases than the United States."} +{"text": "In the published article, there was an error in affiliation 4. Instead of \u201cDepartment of Cardiovascularology, the Affiliated Donghua Hospital of Sun Yat-sen University, Guangzhou, China\u201d, it should be \u201cDepartment of Cardiovascularology, Tungwah Hospital of Sun Yat-sen University, Dongguan, China.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Faced with the COVID-19 pandemic, the world was forced to adopt strong public health measures, such as travel restrictions, physical distancing, and self-isolation. Prolonged periods of self-isolation, like the one imposed by the ongoing pandemic, may have serious repercussions on people's mental health . For exaWe conducted a search on August 8th, 2020 for peer-reviewed publications in English using three databases: PubMed, ProQuest, and Web of Science. We searched for publications that had the following keywords in their titles: \u201calcohol\u201d or \u201cdrinking\u201d or \u201csmoking\u201d or \u201cnicotine\u201d or \u201ccigarette\u201d or \u201ccigarettes\u201d or \u201ccigar\u201d or \u201ccigars\u201d and \u201cCOVID-19\u201d or \u201cpandemic\u201d or \u201cSARS-CoV-2,\u201d a search that led to ~300 publications. We found two publications regarding potential changes in tobacco use patterns due to the pandemic in the general population. One, a study describing a survey conducted in the United States of America (USA), where almost half of the respondents reported no changes in their smoking patterns, and about a quarter reported having reduced their cigarette smoking . There wRegarding alcohol use, we found a publication reporting an increase in alcohol sales during the early stages of the pandemic in the UK . We alsoTo complement this search, the authors also looked for country-specific information regarding restrictions on alcohol and tobacco sales, if there were any, and changes in patterns of alcohol and tobacco use in their respective countries. To conduct this search, the first and last authors invited fellow mental health professionals, members of a team connected through the World Psychiatric Association (WPA) , to sharRestrictions on alcohol sales as a response to the pandemic vary among countries represented in our team, within a continuum that goes from total alcohol ban to no restrictions besides those caused by physical distancing. In India, for example, there was a nationwide alcohol ban during initial stages of lockdown , which sIn most countries, however, even during stricter lockdown periods, alcohol sales have been allowed in liquor stores, supermarkets, and retailers. In Nigeria, alcoholic beverages are considered essential commodities, with liquor stores exempted from the lockdown , despiteThere have been no restrictions on tobacco sales in any of the contributing authors' countries. However, in Colombia, cigar shops can only remain open as long as they also distribute food and basic necessities. In India and the USA, accessibility to tobacco via retailers has varied across states. In the USA, there were reports of tobacco sale increases , 37. An Our findings concur with the suggestions made by other authors that, during the COVID-19 pandemic, tobacco and alcohol use patterns have been influenced by societal and cultural processes, as well as by local alcohol control policies , 41. We The pandemic has led the world to recognize the need for global action in order to support people's health and well-being. It is necessary for all countries to develop measures that will support the entire population during this time of crisis, including people with a substance use disorder. These measures should incorporate effective demand, supply, and harm reduction strategies to reduce risky substance use and substance-related harm. In regard to alcohol and tobacco, potential ways forward include revising local alcohol and tobacco licensing systems and reducing hours of sale, reducing availability via carry out and delivery services, promoting help seeking and reducing stigma around it, providing sustained public health promotion campaigns, and fostering diversion initiatives that could be conducted while observing physical distancing. It is of the utmost importance for any strategy to be evidence informed, locally relevant, culturally appropriate, and equitable. In other words, it is relevant and necessary local actions that would lead to global impact, and the time for action is now.RRam and PG developed the concept of this manuscript and discussed it with FA, DG, SE, JG-D, AL, LO, VP-S, MPC, RRan, MS, and ZS. FA, DG, SE, JG-D, AL, LO, VP-S, RRan, MS, ZS, and PG provided country-specific information. RRam and PG wrote the initial draft and FA, DG, SE, JG-D, AL, LO, VP-S, MPC, RRan, MS, and ZS edited and approved the final version for submission. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the published article, there was an error regarding the affiliations for Zhan-Qiang Wang, Kuo Li, Tian-Tian Huo, and Pei-Yuan Lv. All of these authors are also affiliated to the Department of Neurology, Hebei Medical University, Shijiazhuang, China.Additionally, there was an error in the original affiliation 3, now amended to be affiliation 4. Instead of \u201cDepartment of Neurology, Cangzhou Central Hospital, Cangzhou, China\u201d it should be \u201cNo. 2 Department of Neurology, Cangzhou Central Hospital, Cangzhou, China.\u201dThe authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-020-59120-1, published online 10 February 2020Correction to: In the original version of this Article, Alice Ballone was incorrectly affiliated with \u2018Faculty of Biosciences, and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy\u2019. The correct affiliation is listed below.Barcelona Biomedical Research Park (PRBB), University of Pompeu Fabra and Icrea, Barcelona, Spain.This error has now been corrected in the PDF and HTML versions of the Article."} +{"text": "Michael L. Beeton was not included as an author in the published article. The corrected Author Contributions Statement appears below.in vivo model and performed the animal experiments. CH carried out the laboratory analyses with the support from NR, LK, and GR. CH, IL, MH, KL, VM, WB, BK, WG, and TW contributed to the interpretation of the results. CH and IL wrote the manuscript with the input from all authors. WG and TW supervised the project. All authors contributed to manuscript revision, read, and approved the submitted version.CH, IL, MH, WG, and TW conceived the original idea. MS, HU, SS, OS, MB, MP, JN, AJ, and MK designed the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Journal of Animal Science and Technology, \u201csince May 2020, the article processing time has stably decreased. It is believed that the article processing time will continue to become shorter, as time spent at home will increase in the future\u201d [Journal of Educational Evaluation for Health Professions (JEEHP) is not an exception. The number of submitted manuscripts has increased by 95% in 2020 . JEEHP has also published some articles related to COVID-19, including an editorial [This year began with the spread of the coronavirus disease 2019 (COVID-19) pandemic, which has dramatically influenced all aspects of life for people throughout the world, including editors. A striking trend has been a marked increase in the number of submissions to journals. For instance, the number of submitted manuscripts increased by 42% in 2020, compared with an average expected increase of 11% during 2016\u20132019, in the neurosurgical, stroke neurology, and neurointerventional literature [ future\u201d . The Jouditorial .There is still no substantive, evidence-based reason to think that the present situation will change until at least the end of 2021. Despite promising advances in vaccine development and chemotherapeutic drugs, large-scale trials will be necessary to determine their efficacy.The COVID-19 pandemic has presented tremendous challenges for teachers and instructors at all levels of education. At my medical school, lectures have moved online in the form of video files or real-time lectures, but laboratory and clinical practice has continued to involve face-to-face activities from February to November of this year. Personally, as an instructor, I have found it difficult to implement problem-based learning or team-based learning (TBL) through an online platform. The issue is not that the transition to an online environment is likely to diminish students\u2019 academic performance, since medical students in Korea are excellent at organizing their knowledge and acquiring skills; instead, the problem relates to the thought processes instilled by student-centered learning which enables the mutual learning and growth among peers. I wonder whether the transition to online learning may affect graduates\u2019 competency, including social relationships. In Singapore, an online TBL platform was provided to teachers and students. In this system, the group of students could communicate through a separate communication platform, distinct from class-wide discussions . The imphttps://www.jeehp.org/).I received a letter from an author who submitted a manuscript to the journal this August, stating that she stopped the procedure \u201cbecause the journal is not indexed in Journal Citation Report (JCR).\u201d This manuscript had already been revised twice according to the reviewers\u2019 and editors\u2019 comments\u2014in other words, the manuscript was withdrawn at the stage of its final acceptance. Reviewers\u2019 and editors\u2019 time should not be wasted in this way. I have been frequently asked whether JEEHP is indexed in Science Citation Index Expanded (SCIE). The indexing and abstracting status of JEEHP is clearly presented on its website in health education. I am not sure when the JEEHP will be listed in SCIE, as desired by many potential authors. If the 2-year impact factor reaches the 2nd quartile in the corresponding category, it will be re-evaluated by Clarivate Analytics. However, JEEHP still did not reach that status in 2020, as described below.In a recent article, Tennant sharply The countries of the authors who published articles in JEEHP this year, as well as the total cites from Scopus, Web of Science Core Collection, and Crossref metadata, were analyzed. The 2-year impact factors calculated by the Web of Science were also calculated for recent years, although these are not official impact factors. In 2020, half of the articles were from Korean authors . This laKorean Journal of the Academic Society of Nursing Education, and 4 from the Korean Medical Education Review. One review was the report from the Korean Institute of Medical Education and Evaluation (KIMEE). The 2 educational/faculty development materials consisted of 1 guideline published in a booklet on extravasation and 1 training material containing the Korean Government\u2019s guideline on COVID-19 infection when caring for a patient or suspected case\u201d has been cited 50 times according to Crossref metadata will be Due to the increased number of submissions, 74 reviewers from 19 countries were invited this year. Without their help, it would not be possible to publish the journal. JEEHP is deeply indebted to them. Below are the reviewers\u2019 names and affiliations by country.Australia: Michael Field, University of Sydney; Boaz Shulruf, University of New South WalesArgentina: Raul Alfredo Borracci, Austral UniversityCanada: Oksana Babenko, University of Alberta; Armson Heather, University of CalgaryChina: Yanhua Yi, Guangxi Medical UniversityDenmark: Steven Arild Wuyts Andersen, RigshospitaletIndia: Irfan Ali, Great Eastern Medical School and Hospital; Thalanjeri Padmini, Yenepoya Medical College; Khanna Vinay, Manipal Academy of Higher EducationIran: Mohammad Esmaiel Hajinezhad, Iran University of Medical ScienceItaly: Fabrizio Consorti, Universit\u00e0 Sapienza of RomeKorea: Duck Sun Ahn, World Federation for Medical Education; Hyung-Joon Ahn, Yonsei University; Ara Cho, Catholic University of Korea; Younyoung Choi, Hanyang Cyber University; Kyungsook Choi, Chung-Ang University; Cheol-Woon Chung, Catholic Kwandong University; Young Eun, Gyeongsang National University; Geum-Hee Jeong, Hallym University; Sunho Jung, Kyunghee University; Min Hyeok Kang, Busan Catholic University; Chul-Gyu Kim, Chungbuk National University; Sue Kim, Yonsei University; Sun Kim, Catholic University of Korea; Youngjon Kim, Wonkwang University; Ji-Woon Ko, Sunmoon University; Suk Bong Ko, Catholic University of Daegu; Young Hwan Lee, Yeungnam University; Kyunghee Lee, Shinhan University; Sujung Lee, Hallym University; Yonghee Lee, Korea University; Eunyoung Lim, Korean Institute Curriculum and Evaluation; Deuk-Sang Ma, Gangneung-Wonju National University; Mikyung Moon, Kyungpook National University; Younjae Oh, Hallym University; Bohyun Park, Changwon National University; Kwi Hwa Park, Gachon University; Dong Gi Seo, Hallym University; Yeonok Suh, Soonchunhyang University; Eun Young Suh; Seoul National University; Sanghee Yeo, Kyungpook National University; Mira Yun, Chung-Ang UniversityMexico: Gonzalez Fernanda, Universidad Aut\u00f3noma de TamaulipasPakistan: Gardezi Syed Adeel Hussain, Combined Military Hospital; Khadija Qamar, Aga Khan University; Iqbal Waseem, College of Physicians and Surgeons PakistanPalestine: Ramzi Shawahna, An-Najah National UniversitySaudi Arabia: Mohammed Abdulrahman, King Saud bin Abdulaziz University for Health Science; Badr Alsayed, University of Tabuk; Amira Fraghely, Prince Sattam Bin Abdulaziz UniversitySpain: Jorge Riqueleme Galindo, University of AlicanteUnited Arab Emirates: Indira Kannan, Tawam HospitalUK: Cleopatra Branch, Universities of Greenwich and Kent; Aaron Courtenay, Ulster University; Matt Homer, University of Leeds; Adam Rathbone, University of NewcastleUSA: Neeka Akhavan, University of Florida; Lynch Amanda, Oakland University; Erin Breitenbach, A.T. Still University; Stalvey Carolyn, University of Washington; Cathy Chang, Baylor College of Medicine; Eugene Jones, University of Texas Southwestern Medical Center; Myunghee Jun, University of Wisconsin-Green Bay; Linda Konecny, A.T. Still University; Sara Lolar, Wayne State University; Anna Miller-Fitzwater, Wake Forest Medical School; Takara Page, Ascension Health; Betty Del Rio Rodriguez, Baylor College of Medicine; Thongpriwan Vipavee, University of Wisconsin-Milwaukee; Hon Yuen, University of Alabama at BirminghamZambia: Aubrey Chichonyi Kalungia, University of Zambia; Ogah Nike, University of ZambiaCountry unidentified: Manguiat Jose-SebastianTom Huh, a graduate student of the Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea, voluntarily made the audio recordings of some abstracts.I will consider adopting artificial intelligence for editing and publishing . Some prThe editor\u2019s job has been very hard for me since the beginning of the COVID-19 pandemic due to the rapid increase in submissions. As mentioned above, 230 manuscripts were rejected without peer review. Rejecting a submission is a serious decision, and the editor and the editorial team should read manuscripts thoroughly before making that choice. Furthermore, more reviewers should also devote themselves to reading manuscripts and writing reviews. Next year, we will do our best to select more scientifically described and well-written articles according to the journal\u2019s style and format in order to save the reviewers time and to reduce their burden.The COVID-19 pandemic may last until the end of 2021. We have trained medical and health personnel to combat this viral disease and to reduce its burden. Thanks to our collective efforts, the day will soon come when we will again be free from the present pandemic. I hope that all of the readers, authors, and reviewers of JEEHP will stay safe and be healthy in this pandemic period."} +{"text": "In \u201cEstimated Sleep Duration Before and During the COVID-19 Pandemic in Major Metropolitan Areas on Different Continents: Observational Study of Smartphone App Data\u201d :e20546) the authors noted one error.In the originally published paper, the name of one author cited in Reference 25 (Czeisler M\u00c9) was incomplete. The list of authors cited in Reference 25 originally appeared as follows:Czeisler M, Howard ME, Robbins R, Barger LK, Facer-Childs ER, Rajaratnam SM, et al.In the corrected version of the paper, the list of authors appears as follows:Czeisler M\u00c9, Howard ME, Robbins R, Barger LK, Facer-Childs ER, Rajaratnam SM, et al.The correction will appear in the online version of the paper on the JMIR Publications website on February 22, 2021, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cDepartment of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical University, Guizhou, China\u201d, it should be \u201cDepartment of Cerebrovascular Disease, Affiliated Hospital of Zunyi Medical University, Guizhou, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We are waging a war against a deadly virus that has already resulted in the death of thousands of people worldwide in middle-aged master athletes should be avoided. Nevertheless, in times as these of a pandemic and social isolation, it is important to avoid deconditioning as it will weaken the immune function and diminish the defense against viral infections (Agha et al., The higher physical fitness, better health, lower inflammation, better redox balance, and the longer leukocyte telomere length of master athletes indicates they are not only biologically younger than their calendar age suggests, but are also expected to have a better ability to successfully face a COVID-19 disease than their frail sedentary age-matched peers .HS proposed the subject. HS, TR, CS, SA, MK, HD, and CC discussed the hypothesis and the manuscript content. HS wrote the first draft, with CS, SA, MK, and HD making initial revisions. All final revisions were shared and had contributions of HS, CC, DM-S, SA, TR, MK, and HD. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Djuro Ma\u00e7ut. The correct spelling is Djuro Macut. In addition there was an error in affiliation 7. Instead of \u201cDepartment of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia,\u201d it should be \u201cClinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.\u201dIn the article, an author's name was incorrectly spelled as The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In \u201cEffectiveness of an 8-Week Web-Based Mindfulness Virtual Community Intervention for University Students on Symptoms of Stress, Anxiety, and Depression: Randomized Controlled Trial\u201d :e18595) the authors noted two errors.Member names of the group author \u201cMVC Team\u201d were not added to the PubMed listing of this article at the time of publishing. All member names have now been added as collaborators on the PubMed listing, as follows:Sahir Abbas, Yvonne Bohr, Manuela Ferrari, Wai Lun Alan Fung, Louise Hartley, Amin Mawani, Kwame McKenzie, Jan E Odai.As well, MVC Team was incorrectly noted as having contributed equally. This note has been removed from MVC Team. Only Christo El Morr, Paul Ritvo, and Farah Ahmad contributed equally.The correction will appear in the online version of the paper on the JMIR Publications website on September 30, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "COVID-19 has severely affected people's health and well-being, including all economic sectors, tourism, culture, and education. Along with combating the COVID-19 epidemic, fighting the \u201cinfodemic,\u201d which refers to the rapid spread of misinformation, related to the disease on the social media is also of concern, because fake news spreads faster and easier than this virus, and just as dangerous .In Vietnam, the role of press and social media in spreading the government's information regarding COVID-19 pandemic is undeniable; however, fake news phenomenon is still substantial. A report of the Ministry of Information and Communications revealed that from 01/02 to 05/31/2020, the press had published a total of 560,048 news and articles about COVID-19 translation. According to the statistics of the police force, from the onset of the Covid-19 epidemic to the middle of March 2020, there were nearly 300,000 news articles on cyberspace, posts on websites, blogs, forums, and almost 600,000 news, articles, videos and clips related to the disease posted on social networks (Massive media bombardment regarding the lockdown period led to public speculation in Vietnam, as in many parts of the world, which was the cause of grocery shortages and great consequences. Supermarkets and grocery stores revealed out-of-stock of antibacterial gels, antibacterial wipes, detergents, and toilet paper, while pharmacy stores reported the shortage of isopropyl alcohol, latex gloves, and medical-grade masks , leadingIn response to fake news, especially during the COVID-19 pandemic, the government has made early predictions and concrete strategies. Since June 12, 2018, the National Assembly of Vietnam passed a cybersecurity law comprising seven chapters and 43 articles that stipulated activities to protect national security, ensure social order and safety on cyberspace, and responsibilities of agencies, organizations, and individuals involved . CyberseMoreover, the government needs to pledge to be transparent in providing information, helping people grasp promptly and take measures to prevent and fight epidemics. Solving this method also helps people have faith in the official news of the state. However, the most important thing is that every internet user needs to be alerted to select reliable information and respect seriously for Vietnamese law. Furthermore, health professionals and health workers should regularly transfer necessary knowledge about disease prevention and control to people on the social network.TTPN, DCN, ATTN, and LHN: conceptualization. TTPN, DCN, and ATTN: writing\u2014original draft. LHN, TTPN, DCN, ATTN, GTV, CTN, THN, and HTL: writing\u2014review and editing. CTN, THN, LHN, and GTV: project administration. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In randomized trials, the term \u201cdouble-blind\u201d has no standard or widely accepted definition. Agreement about which groups are blinded is poor, and authors using these terms often do not identify which groups were blinded, despite specific reporting guidelines to the contrary. Nevertheless, many readers assume\u2014incorrectly\u2014that they know which groups are blinded. Thus, the term is ambiguous at best, misleading at worst, and, in either case, interferes with the accurate reporting, interpretation, and evaluation of randomized trials. The problems with the terms have been thoroughly documented in the literature, and many authors have recommended that they be abandoned.We and our co-signers suggest eliminating the use of adjectives that modify \u201cblinding\u201d in randomized trials; a trial would be described as either blinded or unblinded. We also propose that authors report in a standard table which groups or individuals were blinded, what they were blinded to, how blinding was implemented, and whether blinding was maintained. Individuals with dual responsibilities, such as caregiving and data collecting, would also be identified. If blinding was compromised, authors should describe the potential implications of the loss of blinding on interpreting the results.\u201cDouble blind\u201d and its derivatives are terms with little to recommend their continued use. Eliminating the use of adjectives that impart a false specificity to the term would reduce misinterpretations, and recommending that authors report who was blinded to what and how in a standard table would require them to be specific about which groups and individuals were blinded. The single biggest problem in communication is the illusion that it has taken place. George Bernard ShawIn reports of randomized trials, the use of the term \u201cdouble-blind\u201d and its derivatives is commonly understood to indicate that two groups participating in the trial are kept unaware of which participants are receiving the experimental intervention and which are receiving the control intervention \u20136.Despite its long and widespread use, however, the term has several problems.Agreement about which groups are blinded in a double-blind trial is poor \u201316. For Even when using the term in an article, many authors do not identify which groups were blinded or how blinding was implemented , 16, 17.Many readers assume\u2014incorrectly\u2014that they know which groups are blinded in a double-blind trial Table\u00a0 2\u20135, 11, 16. UnfThe suggestion to establish explicit definitions for the term , 18 is cbefore participants have been assigned to experimental groups, whereas blinding minimizes surveillance, expectation, and ascertainment bias after group assignment. Many readers are not aware of this difference [In randomized trials, the allocation schedule has to be kept secret to prevent group assignment from being manipulated. That is, allocation concealment minimizes selection bias fference , 18\u201320, \u201cA randomised trial can be methodologically sound and not be double blind or, conversely, double blind and not methodologically sound.\u201d . Said anhow treatments are made indistinguishable [which groups are unaware of treatment assignment [Some authors prefer \u201cmasking\u201d to \u201cblinding,\u201d although the meaning of either term in a clinical trial may not be readily apparent to nonnative English speakers , 22. Furuishable , 25, 26,signment \u20136. FinalThe problem with trying to identify in a single term the groups who are blinded in a trial is that the number of pairs is potentially large. The literature identifies 11 groups or individuals who could be blinded: participants, care providers, data collectors and managers, trial managers, pharmacists , laboratAs near as we can tell, despite the above problems and several calls to abandon the term , 16, 28,The terms \u201cfully blinded\u201d or \u201cpartially blinded\u201d do appear in the literature, but not as substitutes for substitutes for double-blinding or single-blinding . AlthougWe considered blinding \u201cassignment concealment \u201d becauseHowever, assignment concealment does not work well as a label. We concluded that \u201ca concealed assignment trial\u201d was unlikely to replace \u201ca blinded trial.\u201d Likewise, its use can be awkward: \u201cgroup assignment was concealed from participants\u201d was unlikely to replace \u201cparticipants were blinded to treatment.\u201d Further, as noted above, for better or worse, the mere use of the term \u201cblinding\u201d is widely considered to indicate study quality, and we concluded that authors would be unwilling to give up using this prized and familiar term. Finally, many people believed that \u201cconcealment\u201d should be reserved for, or would be confused with, allocation concealment.The term \u201cblinding\u201d is so firmly established that a simple substitute term, even if we could find one, is unlikely to be acceptable. Instead, we propose two changes in reporting trials described as blinded.Our first proposal is to eliminate the use of adjectives that modify \u201cblinded\u201d: single-, double-, triple-, observer-, personnel-, rater-, observer-, fully or partially blinded, or any other qualifier that would make \u201cblinded\u201d seem more specific than it is. A trial would be described as either blinded or unblinded. Using \u201cblinding\u201d as a verb in a sentence would also be helpful. Such use encourages specificity by requiring a noun, usually which groups were blinded: \u201cWe blinded caregivers and data assessors\u201d or \u201ccaregivers and data assessors were blinded.\u201dWe wholeheartedly endorse the near-universal recommendation that authors report whether or not the trial was blinded , 14\u201316, was or was not blinded, what information they were blinded to, how blinding was implemented, and whether blinding was maintined during the trial. The supplemental part, used when necessary, would present the same data for any other group or individual who was blinded. Individuals with dual responsibilities, such as caregiving and data collecting, would be identified in the same row heading. If blinding was compromised, authors should report the fact in the table and indicate in the text the potential implications that loss of blinding might have for interpreting the results.Accordingly, our second proposal is to have all trials described as blinded include the details in a standard \u201cWho Knew\u201d table Table\u00a0. This ta\u201cBlinding\u201d as a concept to reduce bias has been used for more than 200\u2009years , and \u201cdoThomas A. Lang, MAPrincipal, Tom Lang Communications and Training InternationalAdjunct Instructor, Medical Writing and Editing Program, University of Chicago Professional EducationSenior Editor, West China Hospital/Sichuan Medical School, Chengdu, ChinaDonna F. Stroup, PhD, MScPrincipal, Data for Solutions, Inc.Adjunct Instructor, Medical Writing and Editing Program, University of Chicago Professional EducationCo-signers :Matthias Egger, MD, MSc, FFPH: Professor of Epidemiology and Public Health and former Director, Institute of Social and Preventive Medicine, University of Bern, and President, National Research Council, Swiss National Science Foundation. Former co-editor, International Journal of EpidemiologyForough Farrokhyar, MPhil, PhD: Professor and Research Director, Department of Surgery, Department of Health, Evidence and Impact, McMaster UniversityRobert Fletcher, MD: Professor Emeritus of Population Medicine, Harvard Medical School; founding Co-Editor, Journal of General Internal Medicine; former Co-Editor-in-Chief, Annals of Internal Medicine; founding member, Word Association of Medical Editors (WAME); member, International Advisory Board, The LancetSuzanne W. Fletcher, MD: Professor Emerita of Population Medicine, Harvard Medical School; founding Co-Editor, Journal of General Internal Medicine; former Co-Editor-in-Chief,\u00a0Annals of Internal Medicine; National Academy of Medicine; former member, American Board of Internal Medicine; founding member, US Preventive Services Task ForceR Brian Haynes, OC, MD, PhD, FRCPC: Professor Emeritus of Clinical Epidemiology and Biostatistics; Professor of Medicine, McMaster University; co-founder, Evidence-Based Medicine movement; founder, Health Information Research Unit; founding Editor, ACP Journal Club; lead developer of the structured abstractAnne Holbrook, MD, PharmD, MSc, FRCPC: Professor, Department of Medicine, and Director, Division of Clinical Pharmacology & Toxicology, McMaster University; leading Canadian drug policy advisor and research lead for evidence-based therapeuticsEileen K Hutton, RM, PhD, DSc (HC): Professor Emerita and former Assistant Dean, Faculty of Health Sciences, and former Director of Midwifery, McMaster University; Professor of Midwifery Science, Vrije University, Amsterdam; and Fellow, Canadian Academy of Health SciencesAlfonso Iorio, MD, PhD, FRCPC: Professor, Department of Health Research Methods, Evidence and Impact; Bayer Chair for Clinical Epidemiology Research and Bleeding Disorders; Chief, Health Information Research Unit and Hamilton-Niagara Hemophilia Program, McMaster UniversityRichard L. Kravitz, MD, MSPH: Professor, Internal Medicine; Former Director, Center for Health Services Research in Primary Care, University of California, Davis; former co-Editor-in-Chief, Journal of General Internal Medicine; Director, UC Center Sacramento, a program providing leadership training in politics and relevant evidence for policymakersJos\u00e9 Florencio F. Lape\u00f1a Jr., MA, MD, FPCS: Professor of Otolaryngology; former Vice-Chancellor, University of the Philippines; Editor-in-Chief, Philippine Journal of Otolaryngology Head and Neck Surgery; Charter President, Philippine Association of Medical Journal Editors; Past President, Asia Pacific Association of Medical Journal Editors (APAME); Secretary and Past Director, World Association of Medical Editors (WAME)Maria del Carmen Ruiz-Alcocer, MD: Senior Medical Editor, Intersistemas Publishers; Former President, Mexican Association of Biomedical Journal Editors (AMERBAC); Past Director, World Association of Medical Editors (WAME); member, European Association of Science Editors (EASE)Roberta Scherer, PhD: Senior Scientist, Clinical Trials and Evidence Synthesis, Johns Hopkins Bloomberg School of Public Health; former Associate Director, USA Cochrane Center; Adjunct Assistant Professor, Epidemiology & Public Health, University of Maryland School of MedicineChristopher H. Schmid, PhD: Professor and Chair of Biostatistics and founding member and former Co-Director of the Center for Evidence Synthesis in Health in the Brown University School of Public Health; founding Co-Editor of Research Synthesis Methods; helped develop Institute of Medicine national standards for systematic reviewsThomas A. Trikalinos, MD: Associate Professor of Health Services, Policy, and Practice; Director, Center for Evidence Synthesis in Health, School of Public Health, Brown UniversityJunmin Zhang, MD, PhD: Professor and Managing Director, Journal of Capital Medical University, Medical Education Management, Journal of Translational Neuroscience, Capital Medical University, Beijing, China"} +{"text": "Due to the growing public awareness of cardiovascular disease (CVD), blood pressure (BP) estimation models have been developed based on physiological parameters extracted from both electrocardiograms (ECGs) and photoplethysmograms (PPGs). Still, in order to enhance the usability as well as reduce the sensor cost, researchers endeavor to establish a generalized BP estimation model using only PPG signals. In this paper, we propose a deep neural network model capable of extracting 32 features exclusively from PPG signals for BP estimation. The effectiveness and accuracy of our proposed model was evaluated by the root mean square error (RMSE), mean absolute error (MAE), the Association for the Advancement of Medical Instrumentation (AAMI) standard and the British Hypertension Society (BHS) standard. Experimental results showed that the RMSEs in systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 4.643 mmHg and 3.307 mmHg, respectively, across 9000 subjects, with 80.63% of absolute errors among estimated SBP records lower than 5 mmHg and 90.19% of absolute errors among estimated DBP records lower than 5 mmHg. We demonstrated that our proposed model has remarkably high accuracy on the largest BP database found in the literature, which shows its effectiveness compared to some prior works. According to a statistical report from the World Health Organization (WHO), cardiovascular disease (CVD) is the leading cause of death worldwide, with an estimated 17.9 million people dying from CVD in 2016, representing 31% of global deaths is denoted as Noise removal: Fast Fourier transform (FFT) is applied to every PPG data segment to convert it from its time domain into the frequency domain. Let x are data points in each PPG data segment {X} and Normalization and 1st and 2nd derivative of PPG calculation (denoted as \u201cdPPG\u201d and \u201csdPPG\u201d): All the raw values of PPG are positive, so min\u2013max normalization is applied to every PPG data segment. The equation of min\u2013max normalization can be represented as (5):Feature point detection: Before feature extraction, a few points should be marked and detected in every cycle of the heartbeat for every signal for cycle segmentation and alignment. Firstly, the systolic peaks of PPG waves of each heart cycle are marked by taking advantage of an algorithm mentioned in . The corPartitioning and abnormal cycle removal: After feature points are located, each PPG data segment and its corresponding dPPG and sdPPG waves are partitioned into fragments by reserving each PPG data segment from one valley point of PPG to the next consecutive valley point of PPG. Abnormal heart cycles are also removed following the criteria mentioned in . After aPrior to the actual process of estimating the blood pressure using PPG signal exclusively, we conduct a preprocessing to enhance the quality of the PPG. The raw PPG data preprocessing consists of four main steps, including noise removal, normalization, feature point detection, and partitioning. The detailed explanation of each step is presented as follows:hr, t1, t2, t3, t4, t5, t6, t7, t8, AS, dAS, sdAS, DS, dDS, sdDS, S1, S2, AA, dAA, sdAA, DA, dDA, sdDA, RAAD, dRAAD, sdRAAD, PI, dPI, sdPI, dVI, sdVI, AID, dAID, sdAID, dDID, sdDID, PIR, dPIR, sdPIR, dRIPV, sdRIPV, AT, dAT, sdAT, DT, dDT, sdDT, dTVO, sdTVO, Slope_a, S3, S4, RtArea, NI, AI, AI1, RSD, RSC and RDC. All the definitions of the 59 features are listed in The candidate features are the 65 features proposed in past studies ,26,27,28thors of observedthors of . ConsequfAn index After feature selection is done, the optimal feature set considered to be highly correlated to BP is obtained. The next step is to train a machine learning model which is able to predict the SBP and DBP values accurately given the selected features. In this work, we use a fully connected deep neural network regressor for this goal. As shown in As a matter of fact, a brain of a human comprises billions of neurons connected each other with synapses, and each neuron communicates through electrical currents. A special kind of machine learning model, called a neural network (NN), was proposed a long time ago to mimic the behaviors of neurons. A generic NN consists of perceptrons, mimicking the function of biological neurons, and an interconnected layered structure that connects every perceptron in one layer to another. Each perceptron contains a weighted vector W and a bias b, as seen in As the development of artificial intelligence has evolved, more and more different kinds of neural networks, such as fully connected networks, convolutional neural networks, and recurrent neural networks, have been proposed to tackle different kinds of problems. Among them, long short-term memory (LSTM) and fully connected neural networks are the most commonly applied regressors for building BP estimation models. Su et al. construcFollowing the methodologies mentioned in \u03b732 \u00d7 2,176,188), including hr, AS, DS, AA, dAA, sdAA, DA, dDA, sdDA, PI, dPI, sdPI, dVI, sdVI, AID, dAID, sdAID, dDID, sdDID, dRIPV, sdRIPV, AT, Slope_a, S3, S4, NI, AI, AI1, RSD, RSC, S1 and S2, is selected as our final feature set. With the help of the Despite the fact that models built from LSTM units are the most frequently and widely applied for time series-related problems, in this study, we choose a different approach. We use a fully connected neural network, which is much simpler in terms of the number of parameters compared to an LSTM unit, to build up our core deep fully connected neural network, serving as a predictor of BP. We conduct tests on several models to determine the optimal number of hidden layers and neurons, following the approach in . Finally\u03b732 \u00d7 2,176,188) is split into three parts, and each part contains 70%, 20% and 10% of the data, which serve as training, testing and validation datasets, respectively. As for the training process, a gradient descent optimizer, called \u201cNadam\u201d [Our model, as shown in \u201cNadam\u201d , is appl \u201cNadam\u201d for sign \u201cNadam\u201d for cardN is the number of total BP samples (SBP or DBP) to be evaluated and There are several mathematical methods and indices that are used to evaluate the validity of the regression model. Among them, the RMSE and MAE between the ground truth of BP and the estimated BP are the most widely used to gauge the performance of a BP estimation model. The definitions of the RMSE and MAE are shown in (10) and (11), respectively :(10)RMSEn (AAMI) and the n (AAMI) . AdditioAn article by the Association for the Advancement of Medical Instrumentation (AAMI) suggestsr, whose value ranges from -1 to 1 and it can be formulated as [r is to measure the degree of correlation between two signals, Pearson\u2019s correlation analysis is one of the most popular methods used to evaluate the validity of a regression model by computing Pearson\u2019s correlation coefficient lated as :(12)r=\u2211iA Bland\u2013Altman plot is used To be honest, it is extremely difficult for us to do a fair comparison with prior works for the following reasons. First, most of the existing models used both ECG and PPG as inputs of the models. Second, even if the inputs of the models were PPG only, it is still difficult to compare them, since the datasets used in different studies may be different. Last, but not least, even if the model to be compared uses the same dataset as our model and also takes only PPG as input, the number of subjects (and cardiac cycles) used for training and testing, which will hugely affect the degree of generalization of a model, may still be different. However, despite all the impediments, it is still necessary to compare our proposed model to other works owing to the fact that through the comparison, we will be able to understand and judge our own model better. The comparison results are shown in From In summary, in this study, we propose a fully connected DNN model to estimate SBP and DBP, from a PPG signal only. We perform feature selection based on big data analysis using 9000 subjects, 2,176,188 records of BP in total and 32 optimal features selected based on the proposed selection index. Finally, our proposed model reaches BHS Grade A and satisfies the AAMI standard. The MAE is as low as 3.21 mmHg and 2.23 mmHg for SBP and DBP, and the RMSE is as low as 4.63 mmHg and 3.21 mmHg for SBP and DBP, which outperforms all existing works using the same dataset (MIMIC II). For future works, we plan to apply other RNN-related models to see if the MAE and RMSE can be further decreased. A sequence to sequence model is also a promising direction for this topic. Phase changes in blood pressure can happen under various influences. Thus, further studies should try to involve the correlation between BP estimation and natural time analysis. Additionally, we would like to implement our model in wearable devices to help people at risk of high blood pressure to monitor their BP continuously in their daily activities. Hence, studies on data from people outside hospital should be conducted."} +{"text": "Geriatric assessment\u2014broadly defined\u2014has become foundational to systems of care for frail elderly people at risk for functional decline, death, intensification of services, and long-term institutionalization. Its key feature is the ascertainment of multiple dimensions of health and health risks: not only medical, but functional, cognitive, psychological, and socioeconomic factors. This multidimensionality is key to systematic screening and targeting using technologies to uncover frail, at-risk elderly people in their neighborhoods, homes, and at various other service contact points, for more intensive evaluation, i.e., \u201ccomprehensive geriatric assessment\u201d, a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional limitations of a frail older person to develop a coordinated plan to maximize overall health with aging . Geriatric care models embedding comprehensive and multidimensional assessment\u2014in the community and in institutions\u2014have been studied for years, with evidence supporting the efficacy of some in improving various outcomes ,3,4. In Geriatrics all relate in some way to the foundational theme of multidimensional geriatric assessment, as they also exhibit the continuing evolution and differentiation of structures and processes of care built upon it. Implemented or anticipated assessment-based models of \u201cco-care\u201d with other specialties, allied health providers, or for special clinical populations, are the subject of several reports [The papers gathered in this Special Issue of reports ,8,9,10. reports ; as pers reports . Attenti reports ,14. The reports . Finally reports ,17. Buhr reports .Undoubtably, the papers appearing here represent only a small sampling of present activity, but they indicate the ongoing relevance of foundational principles as services and care for aging populations expand. New technologies, populations, systems of care and financing, and workforce development strategies will need to hold true to these core principles."} +{"text": "HLRP: Health Literacy Research and Practice , has been amended to include factual corrections. An error was identified subsequent to its original publication. Figure The article \u201cShaping Alcohol Health Literacy: A Systematic Concept Analysis and Review\u201d by Orkan Okan, Gill Rowlands, MBBS, MD, FRCP, FRCGP, Susie Sykes, PhD, and Jane Wills, which was published in the January 2020 issue of"} +{"text": "Scientific Reports10.1038/s41598-020-59596-x, published online 17 February 2020Correction to: The original version of this Article contained a typographical error in the spelling of the author Manickam Ashokkumar, which was incorrectly given as Manickam Ashok kumar.In addition, there was an error in Affiliation 4, which was incorrectly given as \u2018Department of Microbiology and Immunology, Univeristy of Missouri, Columbia, MO, 65211, USA\u2019. The correct affiliation is listed below:Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.Furthermore, the Supplementary Information file omitted an affiliation for Aanand Sonawanne, which is now listed as Affiliation 3.These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information."} +{"text": "Revista da Sociedade Brasileira de Medicina Tropical/Journal of the Brazilian Society of Tropical MedicineTitle: Synanthropic rodents as virus reservoirs and transmittersVol.53:e20190486: 2020 - Page: 4/11 - doi: 10.1590/0037-8682-0486-2019Coronaviridae family; Letovirinae, which has one subgenus, Milecovirus, found only in frogs and a sea hare thus far115, and Orthocoronavirinae, which is found in birds and mammals, and is divided into four genera due to the antigenic and genetic characteristics of the viruses53,116.\u201dHere is the form in which the information is found: \u201cAccording to the International Committee on Taxonomy of Viruses, two subfamilies belong to the Coronaviridae family; Letovirinae, which has one subgenus, Milecovirus, found only in frogs (Microhyla fissipes) thus far115, and Orthocoronavirinae, which is found in birds and mammals, and is divided into four genera due to the antigenic and genetic characteristics of the viruses53,116\u201dIt should be read: \u201cAccording to the International Committee on Taxonomy of Viruses, two subfamilies belong to the"} +{"text": "In \u201cEffects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial\u201d the authors made two corrections.The affiliations for authors Mali S\u00e6ter and Kristina Hermann Haugaawere originally published as:2 ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Oslo, NorwayAnd have been changed to:2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway3ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Oslo, NorwayThe subsequent affiliation numeration has been adjusted to accomodate for this change. The correction will appear in the online version of the paper on the JMIR Publications website on November 15, 2023 together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "TThere is a great and renewed need for discussion in this area, in order to exchange and share experiences at 360 degrees on opportunities, problems, and even failures. With this in mind, this Special Issue, \u201cAssistive Technologies, Robotics, and Automated Machines in the Health Domain: Second Edition\u201d was laun"} +{"text": "In the published article, there was an error in affiliation 2. Instead of \u201cDepartment of Neurological Surgery, Tri-Service General Hospital, Taipei, Taiwan\u201d, it should be \u201cDepartment of Neurological Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "As of 15 May 2023, the COVID-19 pandemic has resulted in a total of 765,903,278 cases and 6,927,378 cumulative deaths worldwide . It is fJS, HL, FC, and SC designed and wrote the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "The quantity and quality of cropland plays an important role in ensuring food security. In order to explore spatiotemporal patterns of the extent to which cropland satisfies people\u2019s grain need, we integrate multi-source heterogeneous data to investigate in which era, and in which region, the cultivated land can meet people\u2019s food demands. It turns out that in the past 30 years, with the exception of the late 1980s, the amount of cropland could satisfy people\u2019s grain needs at the nation scale. However, more than 10 provinces , mainly located in western China and southeast coastal areas, have been unable to meet the grain needs of local people. We projected the guarantee rate to the late 2020s. Our study concludes that the guarantee rate of cropland is estimated to be higher than 150% in China. Compared to 2019, except Beijing, Tianjin, Liaoning, Jilin, Ningxia, as well as Heilongjiang in the Sustainability scenario, and Shanghai in the Sustainability and the Equality scenarios, the guarantee rate of cultivated land will increase in every province in 2030. This study has reference value for the study of China\u2019s cultivated land protection system, as well as important significance for China\u2019s sustainable development. Globally, factors such as population growth, higher incomes and urban lifestyles are driving changes in food demand and consumption, putting pressure on the quantity and quality of land resources ,2. SimilSince the reform and opening up in 1978, after 40 years of spectacular growth, China has become the world\u2019s second-largest economy. The population has increased by almost 40 percent, from 987 million in 1980 to 1.412 billion in 2020 . MeanwhiA great deal of effort has been made in China to safeguard domestic food security. Grain output in China has increased steadily under a series of polices and measures implemented by the Chinese government and farmers, such as the delimitation of farmland protection red line and the construction of well-facilitated cropland, etc . Grain o6 hm2, which was mainly distributed in plains, rapidly expanded and densely populated regions, such as Huang-Huai-Hai Plain, the Yangtze River Delta, the Pearl River Delta, and the Sichuan Basin. Approximately 3.18 \u00d7 106 hm2 of cropland were occupied for construction [Achievements in alleviating and eradicating hunger have increased in recent decades, but challenges remain. For example, land and water resources have never been more stressed and their accumulation is pushing the productive power of land and water systems to their ultimate limit. From 1990 to 2010, built-up land in China increased by 5.52 \u00d7 10truction ,12. In atruction , irrigattruction pose sertruction . More noTherefore, it is of great urgency to rethink deeply about China\u2019s ability to ensure food security under these complex contexts. Many studies have concentrated upon the food security of China in the view of food production ,17, foodThis study includes three steps for the analysis of the past and the future. First, we calculated people\u2019s grain needs based on the population and per capita grain requirements. Then, by taking gain crops sown area, farm crops sown area, grain yield per unit area and cropland area into account, we obtain the cropland requirement. Finally, according to the cropland requirements, cropland guarantee degree was calculated . The folProjections of the level of cropland satisfying people\u2019s grain need in the future are critical to enable a better understanding and anticipation of cropland\u2019s bearing capacity. The climate projections and scenarios assessed by the IPCC based on SSP - RCP framework, have furnished an exhaustive grasp of the restrictions and opportunities for policy action . 2 by the middle of this century, and then returned to 2.6 W/m2 by 2100. In order to achieve such a level of radiative forcing, greenhouse gas emissions (as well as indirect emissions of air pollutants) should gradually decrease over time [The Representative Concentration Pathway 2.6 represents scenarios that lead to quite low greenhouse gas concentrations. This is a scene of \u201cpeak and fall\u201d. Its radiative forcing level first reached about 3.1 W/mver time . Under Rver time . The Repver time .The Shared Socioeconomic Pathway describes possible changes in various aspects of society in the 21st century, such as population, economy, technology, society, governance and environmental factors. The purpose is to promote a comprehensive analysis of future climate influence, vulnerability, adaptation and mitigation ,32. In SIn this study, people\u2019s grain consumption was considered as the grain demand by people.Ration and feed grain were two parts that people needed, and the calculation of grain demand is:(1)RationThe calculation of ration consumption in rural and urban areas is the same with previous study , and it (2)Feed GrainThe method of calculation of feed grain in rural and urban areas is similar to the previous study , which cHere, we take the calculation of The calculation of the amount of grain needed in the people\u2019s consumption of pork in rural areas is the same as the calculation in urban areas.However, there are some differences:First, the change in feeding structure has been taken into account when calculating feed grain. The details are as follows:Forage required per unit of product in 1989 and 1999 is based on the research results of Wang Minli and other researchers of the Institute of Agricultural Economy and Development, Chinese Academy of Agricultural Sciences . With soSecond, the proportion of edible parts of meat, aquatic products, milk and eggs and the loss of production and circulation are considered. The proportion of edible parts was 65.9%, 55.6%, 100% and 85% respectively, and the loss proportion was 15%, 34%, 6% and 10% respectively [m is the grain yield per unit area; n is the percentage of the area sown by grain crops in the area of cultivated land; k is multiple-crop index, which means the ratio of crop sown area to cultivated area. The definition of cropland requirement is as below:Data from 1989 to 2019 used in this part can be seen and calculated from m: Due to the bottleneck of per unit yield potential of cultivated land, when the per unit yield level continues to increase and approaches the maximum per unit yield potential, the potential for per unit yield increase will gradually decrease. The function curve of exponential decay model can better reflect this change trend. This paper assumes that the external environment disturbance variable of crop growth is constant, that is, without considering crop improvement factors, we can use the grain yield data over the years (1997\u20132020) to build regression analysis models of every province, and the formula is as follow:2; t. n and k in 2030 originated from previous studies, which were 0.68 and 1.2 respectively. In this study, the values of Guarantee level of cropland is defined as:Six categories of data were applied in this study, including population, per capita grain requirement, cropland, per unit area grain yield, sown areas of farm crops, and sown areas of grain crops , the detThe population in 1989, 1999, 2009 and 2019, as well as population in rural and urban areas in 2009 and 2019 was collected from China Statistical Yearbook 1990, China Statistical Yearbook 2000, China Statistical Yearbook 2010 and China Statistical Yearbook 2020 ,5,36,37.https://dataguru.lu.se/app#worldpop, accessed on 2 September 2022) [Population data in 2030 under three scenarios were accessed from the high resolution data set for global future population developed with RCP and SSP scenarios (er 2022) . Population of each province from 1989 to 2030 can be seen from People\u2019s needs for grain include ration and feed grain. Therefore, per capita food consumption is necessary in the calculation of ration and feed grain. The data for per capita food consumption in rural and urban area in 1989, 1999, 2009, and 2019 were obtained from China Statistical Yearbook 1990, China Statistical Yearbook 2000, China Statistical Yearbook 2010 and China Statistical Yearbook 2020 ,5,36,37.The data on per capita food consumption in rural and urban areas in 2030 were from the China dietary nutrition guidelines .https://www.resdc.cn/, accessed on 8 October 2022).The cropland data for 1989, 1999, 2009 and 2019 were obtained from the 1-Km land remote sensing data in 1990, 2000, 2010 and 2020 . And the amount of cropland in each province can be seen from Gridded 1km land use/land cover change projections of China under comprehensive SSP-RCP scenarios of 2030 were used to obtain the cropland for 2030 of 2030 is 1.92 \u00d7 10e lowest .To capture the regional heterogeneity of grain needed by people, we disaggregate grain consumption into five categories from low to high: Lowest (<3); Medium low (3\u2265 and <9); Low (9\u2265 and <15); Medium high (15\u2265 and <21); Highest (\u226521). There are distinct patterns of the amount of grain needed by people : for exaA look at demand patterns over time provides insight into the amount of grain needed by people . Over thDelineating cropland by group is critical to understanding cropland demanding trends. Provinces in the western part of China led in cropland demand from 1989 to 2009. In 2019 and 2030, it can be seen that the southeastern coastal areas, from Huang Huai Hai Plain to Sichuan Basin areas, and northwest areas play major role in the demand for cropland . In the past thirty years, the guarantee rate of cultivated land in the other provinces has declined, with the exception of Beijing, Tianjin, Shanghai, Zhejiang, Fujian, Guangdong, Guangxi, Hainan, Sichuan, Tibet, and Qinghai .In 1989, cropland in Tianjin, Shanxi, Inner Mongolia, Liaoning, Jilin, Heilongjiang, Shanghai, Hainan, Guizhou, Yunnan, Tibet, Shaanxi, Gansu, Qinghai, Ningxia, and Xinjiang could not meet people\u2019s grain needs. Cropland in Sichuan, Jiangsu and Fujian met people\u2019s grain needs to a great extent. While the cropland of the remaining provinces was able to satisfy people\u2019s grain need basically.In 1999, the cropland in Beijing, Tianjin, Shanxi, Liaoning, Shanghai, Yunnan, Tibet, Shaanxi, Gansu, Qinghai and Xinjiang was unable to meet people\u2019s grain need. Cropland in Heilongjiang, Jilin, Hebei, Shandong, Henan, Hubei, Anhui, Jiangsu, Hunan, Jiangxi, Zhejiang and Guangxi met people\u2019s grain need to a great extent. While the cropland in other provinces was able to satisfy people\u2019s grain need basically.In 2009, cropland in Beijing, Tianjin, Shanxi, Liaoning, Shanghai, Zhejiang, Fu-jian, Guangdong, Hainan, Tibet, Shaanxi, Gansu and Qinghai could not meet people\u2019s grain needs. Cropland in Inner Mongolia, Ningxia, Heilongjiang, Jilin, Hebei, Henan, Shandong, Jiangsu, Anhui, Hubei, Hunan, Jiangxi and Guizhou met people\u2019s grain need to a great extent, while the cropland of the remaining provinces was able to satisfy people\u2019s grain need basically.In 2019, the cropland in Beijing, Tianjin, Shanghai, Zhejiang, Fujian, Guangdong, Guangxi, Hainan, Tibet, Shaanxi and Qinghai was unable to meet people\u2019s grain need. Cropland in Xinjiang, Inner Mongolia, Ningxia, Heilongjiang, Jilin, Hebei, Henan, Shandong, Jiangsu, Anhui, Hubei, Hunan, Jiangxi, Guizhou and Yunnan met people\u2019s grain need to a great extent, while the cropland of the remaining provinces was able to satisfy people\u2019s grain need basically.Under the Sustainability, the Middle Road and the Inequality scenarios, apart from Beijing, Tianjin, Shanghai, Jiangsu, Fujian, Guangdong, as well as Hainan in the Sustainability scenario, all provinces are projected to achieve guarantee rate of cropland greater than 100% . With the exception of Beijing, Tianjin, Liaoning, Jilin, Ningxia as well as Heilongjiang in the sustainability scenario and Shanghai in the sustainability and equality scenario, the guaranteed rate pf cropland is expected to be higher in all provinces compared to 2019 . In this study, we analyzed whether or not cropland in China could satisfy people\u2019s grain needs across geographic and temporal scales. The following conclusions can be drawn:(1) With the exception of 1989, the amount of cropland could meet people\u2019s grain need. Moreover, the ability of cropland to satisfy people\u2019s grain need increased from 1989 to 2009, while decreased from 2009 to 2019. Under the three scenarios in 2030, the guarantee rate of cropland is estimated to be higher than 150%. (2) From 1989 to 2019, the guarantee rate of cultivated land in other provinces decreased except Beijing, Tianjin, Shanghai, Zhejiang, Fujian, Guangdong, Guangxi, Hainan, Sichuan, Tibet and Qinghai. Furthermore, more than 10 provinces , which are mainly located in western China and southeast coastal areas, were unable to satisfy the grain demand of local people. Compared to 2019, all provinces except Beijing, Tianjin, Liaoning, Jilin, Ningxia, and Heilongjiang in the Sustainability scenario, and Shanghai in the Sustainability and the Equality scenarios, are projected to have a higher guarantee rate of cropland in 2030 than in 2019.The demand for cultivated land is the key content of this study. By comparing with the existing research, the demand for cultivated land calculated in 2030 (161 million hectares to 164 million hectares) is slightly higher than the previous research results (about 150 million hectares) , which iFrom 1989 to 2009, under the comprehensive influence of population and per capita grain ration and feed grain consumption changes, the grain consumption demand of the Chinese population changed little, but due to technological progress, the unit yield of cultivated land increased, and the amount of cultivated land required decreased. As a result of urbanization and the project of returning farmland to forests, a large amount of cultivated land in China has been occupied . HoweverChina is a vast country with large regional differences. The differences in natural conditions, diet structure, population development and urbanization process in different regions have led to differences in the cultivated land satisfaction rate in different regions of China. The cultivated land resources in western China are poor, and the problems of soil erosion, desertification and soil salinization are serious ,44,45. TChina now is in a new era of food security. The decline in the area of cultivated land and low utilization efficiency have a very negative impact on the potential productivity of China\u2019s cultivated land. Although the results of this study suggest that the amount of cultivated land in China will be more than 1.5 times of that needed to meet people\u2019s grain needs by 2030, the marginalization of cultivated land in the process of urbanization, the non-agricultural transformation of cultivated land, and the transformation of agricultural cropping patterns to achieve economic benefits have potential impacts on China\u2019s food production. Hence, under the background of food security, we need to reasonably use and control the cultivated land, strictly monitor the quantity of cultivated land, and improve the productivity of cultivated land. In addition, due to the geographical differences in population distribution, cultivated land quantity and cultivated land production potential, cultivated land protection in different regions of China faces various pressures. Therefore, under the strategic background of national food security, each region should actively explore and formulate cultivated land protection policies and agricultural production plans, that are suitable for itself and promote the sustainable development of China\u2019s food production."} +{"text": "Both natural disasters such as wildfires, earthquakes, tsunamis, and hurricanes, as well as man-made disasters such as civil wars, have been known to result in significant mental health effects on their victims.The purpose of this general literature review is to analyze the impact and contribution of social determinants to mental health and resilience following natural and man-made disasters.In this paper, we specifically explore some of the most studied factors relating to vulnerability and protection, such as gender, age, ethnicity, social support, and socioeconomic status on mental health and resiliency in disaster survivors. In addition, several other possible factors were discussed, such as previous trauma, childhood abuse, family psychiatric history, and subsequent life stress.Using key words such as mental health, social determinants, disasters, wildfires, earthquakes, terrorism attacks, and resilience, we conducted a literature search in major scientific databasesA discussion of the implications for public health policy and practice is presentedNone Declared"} +{"text": "PLOS ONE Editors retract this article [The article because PLOS ONE Editors note that primary data were not provided with the article, contrary to the Data Availability statement.The AH, MA, MN, ZI, ML, AM, and JTC did not agree with the retraction. MJ, FMP, SA, MNA, and PA either did not respond directly or could not be reached."} +{"text": "Food is not only a source of nutrition for humans; it also encompasses social, cultural, and psychological dynamics. Understanding of food products, preferences, and practices provides us with knowledge of historical, cultural and contemporary uses . In addiIn the first paper published in this Special Issue, Valli et al. analyze Zorell highlighIn addition, Cipriano-Crespo et al. present Mu\u00f1oz et al. focused In the context of Poland as a particular example in Europe, Raftowicz analyzedRos-Bar\u00f3 et al. carried Dancausa Mill\u00e1n and Mill\u00e1n V\u00e1zquez de la Torre analyzedFinally, in the context of the relationship between food and tourism, Yang et al. focused This Special Issue on \u2018Public Awareness of Food Products, Preferences and Practices\u2019 discusses the conception, protection, and promotion of food from a broad perspective, analyzing food-based experiences, consumption, food cultures, social behavior related to food, and healthy and sustainable food practices. All these papers came from original and innovative international research and case studies that show food, from all perspectives, as it is: a necessary fact that straddles the biological and the social, with strong implications for our daily life. They also invite researchers and decision-makers in the field to look into future lines of research, which will span various different areas, such as artificial intelligence, advances in measuring food carbon footprint, demographic and climate change, the preservation of biodiversity, and other factors that could affect individuals\u2019 food preferences, lifestyle, health, and wellbeing."} +{"text": "After struggling with COVID-19 pandemic for two years, the world is finally recovering from this crisis. Nonetheless, another virus, Monkeypox, is quickly spreading throughout the world and in non-endemic regions and continents, threatening the world to a new pandemic. Twitter as a popular social media has successfully been used for predicting and controlling outbreaks. Much research previously has been done for building early warning systems, trend prediction, and misinformation and fake news detection. Since tweets are not accessible to all researchers, in this work, a publicly available dataset containing 2400202 tweets gathered from May first to December twenty-fifth, 2022 is presented. Twitter developers academic researcher API which returns all the tweets matching a given query was used to gather the dataset. To this end, the full archive search and keywords related to Monkeypox and its equivalents in other languages, i.e. Monkeypox or \u201cmonkey pox\u201d or \u201cviruela dei mono\u201d or \u201cvariole du singe\u201d or \u201cvariola do macoco\u201d were used. The retweets were excluded using the negation operator, and the tweet ids and user ids were extracted and shared with public. Approximately, 1.79 percent (43047 number) of tweets were geotagged. To visualize the geotagged tweets, the longitude and latitude of the bounding box coordinates were averaged. This work will help researchers shed light on the news, patterns, and on-going discussions of Monkeypox on social media, identify hotspots, and help contain the Monkeypox virus. Specifications Table\u2022The COVID-19 pandemic has created havoc throughout the world. After more than two years, just when the Non-Pharmaceutical Interventions (NPI) are being lifted, and the world needs to recover from the damages caused, a new virus, Monkeypox, emerges in more than 20 countries, and threatens the globe to a new pandemic.\u2022NPIs have canceled or postponed many surgeries, diagnostic tests and procedures , causing a great number of patients to fall out of their timeline \u2022It is critical to contain the Monkeypox virus and extinguish the menace. Twitter has previously been successful in early warning systems for outbreaks \u2022Researchers from Data Science, Computer Science, Social Science, Mathematics and Statistics, Medicine and even Economy can use Twitter data further to understanding misinformation/disinformation regarding Monkeypox \u2022The results of the studies could be used by decision-makers to inform more targeted policies, and health officials to provide better services suitable for all communities especially vulnerable and marginalized populations.\u2022Social media platforms such as Twitter are increasingly being used by public to discuss their opinions, concerns, and experiences. This dataset could help researchers understand the popularity of Twitter posts over time, locations and hotspots where people are more concerned, the discussed topics at their hotspots, and sentiments/emotions of the topics of concern.\u2022Previously, a Twitter dataset was prepared for Monkeypox in June 2022 1Each line in the file Monkeypox_May1_to_Dec25_2022.csv is associated with a defferent tweet and includes two columns, TweetID and AuthorID which represent the tweet id and the user id. The file includes 2400202 lines in total. To access the actual tweets and their metadata, the tweet ids need to be hydrated. One software that can hydrate the tweets is DocNow hydrator The tweets belong to 69 different languages. Roughly, 81.82 percent (1963797 number) of the tweets are in English. About 1.79 percent (43047 number) of tweets are geotagged. The longitude and latitude of geotagged tweets were estimated by averaging the longitude and latitude of their bounding box coordinates. Twitter as one of the most popular social media platforms is capable of providing researchers with information to understand the global situation better, and help reduce the number of cases. Therefore, in this work, a dataset containing all the tweets posted since May first to December twenty-fifth 2022 is presented. This dataset can be updated in the future and help researchers overcome various issues regarding the current Monkeypox outbreak.2Twitter API academic researcher account returns all the tweets available with a certain query and allows the user to retrieve ten million tweets per month. The full archive search of the Twitter API academic researcher account was used to retrieve the tweets. This endpoint accepts a query as input which includes a set of keywords and returns all the tweets and their metadata that match the keywords. Since European countries are the hotspots for current Monkeypox virus, the keywords used to build the query included Monkeypox and its equivalents in Spanish, French, and Romanian, i.e., Monkeypox or \u201cmonkey pox\u201d or \u201cviruela dei mono\u201d or \u201cvariole du singe\u201d or \u201cvariola do macoco\u201d. In addition, the retweets were excluded using the negation operator, -is:retweet. The tweets were gathered from May first to December twenty-fifth 2022, and 2400202 number of tweets were retrieved. Other than the actual text, the metadata obtained included tweet id, conversation id, in reply to user id and in reply to username (in case of the tweet being a reply), created at, type , language, retweets count, reply count, like count, geo id, geo-country, geo-province/city, geo-coordinates, author id, author name, author username, author description, author-reported location, author hashtags, created account at, follower count, following count, tweet count, and image URL. However, due to Twitter developers\u2019 privacy policy agreement, only the tweet ids and user ids are shared with the public This dataset complies with the Twitter developers\u2019 API terms of use and privacy policy Zahra M. Nia: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing \u2013 original draft, Writing \u2013 review & editing. Nicola L. Bragazzi: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Supervision, Writing \u2013 original draft, Writing \u2013 review & editing. Jianhong Wu: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Software, Validation, Writing \u2013 review & editing. Jude D. Kong: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Writing \u2013 review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."} +{"text": "The aim of this review was to assess the possible risk factors arising from working conditions, that could have an impact on the stress, fear, and anxiety of construction workers.A systematic review was conducted following the PRISMA format in the Pubmed, Cochrane, Web of Science, Scopus, and PsycInfo electronic databases on February 3, 2023, using the following key words: anxiety, stress, fear, and construction workers. Methodological quality was assessed using the critical appraisal tools of the Joanna Briggs Institute.A total of 35 studies were included. The results showed a number of conditioning factors for stress, anxiety, and fear among construction workers such as age, inappropriate safety equipment, safety culture, high workload and long working hours, physical pain, low social support from direct supervisor or co-workers, lack of organizational justice and lack of reward, financial situation, maladaptive coping strategies, and characteristics of the pandemic.There are a number of risk factors related to working conditions, organizations, and individuals that can affect the levels of stress, anxiety, and fear among construction workers, such as age, work hardship, safety culture and, especially, the long hours that construction professionals work. This may lead to an increase in the number of occupational accidents and higher associated fatality rates.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022367724, identifier: CRD42022367724. The construction sector is currently one of the main productive sectors and economic engines in most countries . It is iThe tasks that construction workers perform may be found to be unsatisfactory for them due to the concurrence of factors related to the work itself, individual characteristics, lifestyle and concomitant health problems, and/or problems related to the professional performance itself , 7. In fStress can be considered as the body's response to frequent and/or continuous mismatches between an individual's demands and the individual's ability to cope with them . This haIt is well known that construction projects often have very tight deadlines. This means that the teams of people who carry out the work, whether they are craftsmen, site teams, supervisors, or technical staff, are under a lot of pressure from their companies. In addition to stress, this can cause anxiety in the worker. Anxiety, according to Spielberger , can be In order to assess the risk factors related to levels of anxiety, stress, and fear among construction workers in the construction industry, a systematic review was conducted following the guidelines of the PRISMA statement . The proThe search was carried out in the Pubmed, Cochrane Library, Web of Science Scopus, and PsycInfo electronic databases on the basis of the keywords that the research question yielded following the PECO strategy .Based on these keywords, the Medical Subject Headings (MeSH) thesaurus was consulted, yielding the descriptors Anxiety, Psychological Stress, Fear, and Construction industry. In order to enlarge the scope of the search, synonymous terms were used to complete the search based on the Medical Subject Headings (MeSH) thesaurus , linked The following inclusion criteria were used for the selection of articles: (1) original articles published in English, Spanish, French, and Portuguese; (2) typology: original articles, meta-analysis, short communications, and case reports; (3) articles published in the last 10 years; and (4) articles measuring any of the following values and/or effects: level of stress, anxiety and fear, number of cases of people with stress/anxiety/fear, substance use, insomnia, physical manifestations of psychological stress, comparison according to type of profession/sex/country, possible risks for the materialization of accidents at work, coping measures, how work and/or psychosocial conditions influence, and health-work relationship and vice versa. Similarly, the exclusion criteria were: (1) studies in a language other than English, Spanish, French, and Portuguese; (2) typology: opinion articles, editorials, and letters to the editor; (3) studies of low scientific-technical quality after applying the quality assessment tool; and (4) articles that did not answer the research question and were not related to the objective of the review.For this search, a pre-established protocol was initially followed for the search and revision strategy in order to minimize the risk of bias in the selection and subsequent publication. This strategy was similar in the different databases by using the aforementioned descriptors and related keywords through the Boolean operators AND and OR. In the drafting of this work, two researchers independently carried out the bibliographic searches. As a secondary strategy, a search was carried out based on the use of references and names of the authors cited in the different records selected with the intention of verifying the existence of works not found in the primary search. For the screening and selection of articles, duplicate studies were eliminated and those articles that could be included were selected after reading the abstract and title according to the previously established criteria. After this initial screening, the same authors analyzed the full articles and selected those studies potentially suitable for inclusion in the review. This selection was made by consensus between the two researchers and any discrepancies that may have arisen were resolved by a third author.Two reviewers independently determined the methodological quality of the selected studies using the critical appraisal tools of the Joanna Briggs Institute (JBI) at the University of Adelaide. These tools allow the assessment of the methodological quality of a study and the extent to which a study has excluded or minimized the possibility of bias in its design, conduct, and/or analysis. The versions for analytical cross-sectional studies (8 items) , for quaA total of 35 studies were selected. The initial search strategies identified a total of 1,150 references, which were then screened according to the topic of this review. Twenty-six of the 35 studies were analytical cross-sectional studies, 2 carried out qualitative research, 6 were mixed methods, and 1 was a quasi-experimental study .Of the 35 selected studies, 8 articles were conducted in China; 4 in the United States, Australia and Korea; 2 studies were conducted in Singapore, Ghana, and India; and 1 study was conducted in Canada, Ethiopia, the Netherlands, Indonesia, Nigeria, the United Kingdom, Pakistan, Saudi Arabia, and Taiwan. In 26 of the 35 selected articles, the sample consisted of construction workers in general, and in 3 of them a distinction was made between workers and supervisors. In another 2, the sample consisted of foreign or migrant construction workers, and the rest had specific characteristics, making a total aggregate sample of 13,399 subjects. As for the topic of research, 31 studies were found on stress, 10 on anxiety, and 3 on fear.The prevalence of substantial mental distress was between 16 and 50% among construction workers , 32 [20,Between 37 and 50% of construction workers showed moderate to extremely severe levels of anxiety , 50. AmoFear among construction workers was mainly associated with the characteristics of the COVID-19 pandemic , 51, witThe different studies showed multiple conditioning factors for stress, anxiety, and fear among construction workers such as age, inappropriate safety equipment, safety culture, high workload and long working hours, physical pain, low social support from direct supervisor or co-workers, lack of organizational justice and lack of reward, financial situation, maladaptive coping strategies, and characteristics of the pandemic.The number of hours worked by employees is a determining factor for the level of stress according to the Occupational Stress Index (OSI). Several studies have found working hours of more than 12 h per day or up toIn many cases, construction projects have to comply with a completion date, and must be finished within that timeframe with the resources that were initially planned. In this sense, many construction workers, despite being fatigued, continue to work for fear of losing their jobs, prioritizing the economic needs of their families over their physical health . LikewisOn the other hand, several of the studies in this systematic review link the age of individuals to mental health , 33, 39.Safety culture is another factor that has been linked to higher levels of stress and anxiety , 34, 43.In this line, the low social support of the direct supervisor or co-workers is a key element as a protective or risk factor, depending on the case , 34, 41.Finally, with appropriate coping techniques, construction workers can improve their stress levels. However, maladaptive coping techniques such as substance use , self-distraction, denial, venting, among others, lead to increased depression, anxiety, and stress , 43, 46.The present study has a number of limitations. Firstly, while the studies included in this review offered valuable contributions to knowledge about the mental health of construction workers, there are not enough studies that encompass the geographical dispersion and socio-cultural differences, types of construction work, and situations that can be encountered in the construction sector. This is why the results found in this review cannot be extended to all construction typologies, company types and sizes, and the important contextual variations that may exist in different regions of the world. Secondly, the multifactorial nature that can give rise to the different risk factors related to mental health makes it impossible to establish a precise interpretation of their cause, as many of these factors are found outside the workplace, such as education, culture, religion, family, or the personal condition of each worker, among others. In this sense, another limitation to be considered is the fact that the different working conditions established in each country at a global level and the laws and customs applied in each one of them in this area hinder the performance of a homogeneous analysis in general terms, as coping behaviors may differ considerably between one place or another, since certain working contexts that could a priori be considered susceptible to harming the health of the worker have become normalized.Accidents at work can be related to the mental health of workers, and age, hardship, and especially the long hours worked by construction professionals are factors that are significantly related to stress, anxiety, and fear. However, further studies are needed in this area that also include different work contexts and variables such as culture, education, professional qualifications, work environment, support systems, among others, in order to establish an early detection of risks.The findings of this review could help construction companies to establish policies toward improving the working conditions of their employees and to increase knowledge about mental health in this sector. In this way, researchers and professionals dedicated to occupational safety, health, and risk prevention can identify these psychosocial factors and establish strategies and proposals to minimize the possible occurrence of such risk factors.The original contributions presented in the study are included in the article/Conceptualization, formal analysis, investigation, writing\u2014original draft, and writing\u2014review and editing: CG-S, JG-I, JG-S, JF-R, JC-V, RA-C, JM-P, and CR-F. Data curation: CG-S, JC-V, CR-F, and JG-I. Methodology, resources, and visualization: CG-S, JG-I, JG-S, JF-R, JC-V, RA-C, and CR-F. Project administration: JG-S, JC-V, and CG-S. Software: CG-S, JG-I, and JG-S. Supervision: JG-S, JG-I, JF-R, RA-C, and CR-F. Validation: JG-I, JC-V, JG-S, RA-C, and JF-R. All authors contributed to the article and approved the submitted version."} +{"text": "Carbon nanotubes (CNTs) were first filled with a number of metals starting in 1993 . Single-Several groups are working on the topic. The groups of Jeremy Sloan in the UK ,5, MariaFirst of all, more substances are waiting to be incorporated into carbon nanotubes. Secondly, the filling of carbon nanotubes opens new possibilities. Third, incorporated substances form new phases inside CNT. Many new works on modeling the atomic structure of filled SWCNTs are forthcoming. Fourth, the filling modifies the electronic properties of SWCNTs. In all cases, the collaboration of researchers around the world is required, which brings new ideas and results. The electronic properties of SWCNTs were first modified and extensively investigated by Marianna V. Kharlamova ,15,16. IA large variety of incorporated substances allows tuning the electronic properties of SWCNTs for targeted applications. Recently, Hisanori Shinohara et al. filled SWCNTs with HgTe, WTe, and MoTe and investigated the electronic properties of filled SWCNTs with spectroscopic techniques ,9. It isSpeaking of applications, most carbon nanotube papers target nanoelectronics, electrochemical energy storage, nanomedicine, thermoelectric power generation, catalysis, sensors, spintronics, and magnetic recording. From one side, all these applications can be developed on an industrial scale. On the other side, the synthesis methods of filled SWCNTs, manipulation, and building device methods are optimized and ready to be implemented in factories. For these reasons, a boom in investigations of filled CNTs is expected. In the Special Issue entitled \u201cApplications of Functionalized Carbon Nanomaterials: Advances and Perspectives\u201d, we focus on applications of chemically functionalized carbon nanomaterials such as carbon nanotubes, graphene, graphene nanoribbons, 2D heterostructures, fullerenes, and nanodiamonds. In my review paper , I summaIn a research paper , the autInterested authors are invited to submit their excellent experimental and theoretical works to this special issue entitled \u201cApplications of Functionalized Carbon Nanomaterials: Advances and Perspectives\u201d."} +{"text": "CA and SE organized the database. CA, MD, and MoM performed the statistical analysis. CrC wrote the first draft of the manuscript. CrC, MD, CG, and MiM wrote sections of the manuscript. MD, CG, and MiM collected data. All authors contributed to manuscript revision, read, and approved the submitted version\u201d.The correct spelling is CCr, GC, RL, VB, and CCo contributed to conception and design of the study. AC and ES organized the database. AC, DM, and MMo performed the statistical analysis. CCr wrote the first draft of the manuscript. CCr, DM, GC, and MMi wrote sections of the manuscript. DM, GC, and MMi collected data. All authors contributed to manuscript revision, read, and approved the submitted version.In the published article, author names were incorrectly written in Conflict of interest section as \u201cCA has received research grants from Almirall, research grants from ECTRIMS-MAGNIMS and honoraria from Almirall, Biogen, Roche Sanofi-Genzyme and Novartis. MoM has received research grants from ECTRIMS-MAGNIMS, UK MS Society, and Merck; and honoraria from Biogen, Merck, Roche, and Sanofi-Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest\u201d.The correct spelling is AC has received research grants from Almirall, research grants from ECTRIMS-MAGNIMS and honoraria from Almirall, Biogen, Roche Sanofi-Genzyme and Novartis. MMo has received research grants from ECTRIMS-MAGNIMS, UK MS Society, and Merck; and honoraria from Biogen, Merck, Roche, and Sanofi-Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The authors apologize for this error and state that this does not change the scientific conclusions of the article in anyway. The original article has been updated."} +{"text": "In the published article, the author names were incorrectly written as \u201cNing Yan, Zi Zhang, San Guo, Shu Shen, Xing Li\u201d. The correct spellings are \u201cNingning Yan, Ziheng Zhang, Sanxing Guo, Shujing Shen, Xingya Li\u201d.In the published article, there was a mistake in the Author contributions. The correct Author contributions appears below.NNY, ZHZ, SJS, and XYL wrote the manuscript. NNY, ZHZ, and SXG prepared Figures and Tables. All authors have reviewed the manuscript and gave their consent to publication. All authors contributed to the article and approved the submitted version.The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article the author names were written in the incorrect order of given and family name. The author name order has been corrected.In the published article affiliation 3 was incorrect. Affiliation 3 has been corrected.The Copyright has been corrected as follows:\u00a9 2023 Ricci, Russo, Renzi, Baldi, Nannini, Lami, Menicatti, Pallecchi, Bartolucci, Niccolai, Cerboneschi, Smeazzetto, Ramazzotti, Amedei and Calabr\u00f2. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The \u201cAuthor contributions\u201d has been corrected as follows:ASC, AA, and ER designed the study. FR, GN, and GL collected the samples. FR, DR, SB, MP, MM, and GB performed the experiments. FR, ER, SB, and EN analyzed the data. MC and MR analyzed microbiota data. ER and FR wrote the manuscript. ER edited the manuscript. AA, DR, and ASC supervised the manuscript. ER, AA, and ASC provided for funding acquisition. All authors have approved the final draft submitted.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Osteichthyes, Cypriniformes in Fauna Sinica was finally completed in 2021. After the efforts of four generations of ichthyologists, the last volume has been officially submitted to the Science Press for printing. The publication of this book is a lifelong dream of the Academician Hsien-wen Wu (The three-volume H.W. Wu) , a famouAcademia Sinica. In the same time, he held a position concurrently as a professor in zoology, anatomy, embryology, and parasitology in the Central University, Fudan University, and Jiangsu Medical College, respectively. His research objects were not only fish, but also included helminths, amphibians, and reptiles. During World War II, the Institute of Zoology and Botany moved from Nanjing to Chonqing, where Professor Wu devoted himself to studies on experimental ichthyology, including physiology and functional morphology such as the mechanism of aerial respiration in fish. From 1940 to 1947, Professor Wu guided his early students, Dr. Jiankang Liu (\u5218\u5efa\u5eb7) and Dr. Xiaowei Zhang (\u5f20\u5b5d\u5a01), the famous ichthyologists in China, in serially publishing many scientific reports on the respiration mechanism of rice eel, exploring in relative detail the structure and function of respiration organ of rice eel based on the morphology, histology, and physiology. In 1950, the Institute of Zoology and Botany was renamed the Institute of Hydrobiology (IHB), Chinese Academy of Sciences (CAS), and moved from Shanghai to Wuhan. From 1964 to 1977, Dr. Wu devoted himself to the editing of the two-volume monograph The Cyprinid Fishes of China , and systematically gave a comprehensive description of freshwater fishes in China University in in China , 1977. Tiformes\u201d . Also, iScience in China in 1981 were not developed until 1970s. Since 1977, encouraged and promoted by Hsien-wen Wu, Yiyu Chen (\u9648\u5b9c\u745c), Xianglin Chen (\u9648\u6e58\u7ca6), and the members of the team have conducted an extensive skeletal study on the representative species in the order Cypriniformes, as well as the descending families such as Cyprinidae, Cobitidae, Homalopteridae, and Catostomidae . They ap in 1981 , and the in 1984 . These p in 1984 .Professor Hsien-wen Wu paid high attention to the collection of fish specimens and emphasized the importance of long-term fieldwork. The team members Yiyu Chen and Wenxuan Cao (\u66f9\u6587\u5ba3) have long devoted themselves to field research on the Qinghai\u2013Tibetan Plateau to collect specimens. Due to their efforts, China currently has the largest collection of cypriniform specimens in the world, and IHB has been rewarded to be one of the world\u2019s leading centers for ichthyology, along with fish research centers in France, Sweden, the United Kingdom, and the United States. Until now, the fish museum founded by Hsien-wen Wu has collected more than 400,000 fish specimens, accounting for more than 1,200 species of fish.Molecular Phylogenetics and Evolution (Science China (Chinese Science Bulletin (Progress in Natural Science (Dr. Hsien-wen Wu emphasized the importance of frontier scientific research, which promoted the rapid development of the ichthyology research team in IHB. Following his heritage, the team has conducted a series of cutting-edge studies, including the evolution of Cyprinidae, Cypriniformes , and plavolution , Sciencece China , ChineseBulletin , Progres Science , and so Science .Fauna Sinica, Osteichthyes, Cypriniformes,\u201d and the launch of the phylogenetic studies on Cyprinidae and Cypriniformes.In summary, Hsien-wen Wu\u2019s great contribution to ichthyological research in China is mainly manifested in the concentrated description of Cyprinidae and Cypriniformes, the publication of \u201cThe Cyprinid Fishes of China,\u201d \u201cHsien-wen Wu\u2019s great contribution also includes the establishment of the largest fish museum in Asia featuring Cypriniformes. After decades of improvement, there are now more than 400,000 fish specimens, about 1,200 species, and more than 260 type specimens housed in the museum."} +{"text": "In the published article, there was an error in the author list, and author Alan Anticevic was erroneously excluded. The corrected author list appears below.1*\u2020, Jure Dem\u0161ar1,2\u2020, Alan Anticevic3,4 and Grega Repov\u01611Nina Purg1Department of Psychology, Faculty of Arts, University of Ljubljana, Ljubljana, Slovenia2Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia3Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States4Department of Psychology, Yale University School of Medicine, New Haven, CT, United StatesIn the published article, there was an error. Alan Anticevic was erroneously excluded from the Author Contributions statement. The corrected Author Contributions statement is below.NP, JD, AA, and GR: conceptualization. JD and GR: methodology and software. NP and GR: investigation and formal analysis. NP, JD, and GR: writing\u2014original draft, writing\u2014review, and editing. AA and GR: resources, supervision, and funding acquisition. All authors contributed to the article and approved the submitted version.In the published article, there was an error. Alan Anticevic was erroneously excluded from the Conflict of Interest statement. The corrected Conflict of Interest statement is below.JD consults for Manifest Technologies. AA and GR consult for and hold equity in Neumora Therapeutics and Manifest Technologies.The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Numerous and heterogeneous populations of beneficial microorganisms originating from raw materials, equipment, and production and processing environments can affect the fermentation process by their metabolic activities, allowing for the enhancement of the nutritional value, sensory characteristics, overall quality, safety, and shelf-life of final food products ,2,3. In On the other hand, multiple sources of the contamination of raw materials, equipment, and environments involved in the manufacturing of fermented foods may allow for the establishment and proliferation of spoilage and pathogenic microorganisms, which can cause alterations in the final products and threaten consumer health ,7.Microorganisms, dedicated to \u201cBeneficial and Detrimental Microorganisms Occurring in Fermented Foods\u201d, aimed at collecting new studies concerning any aspect of pro-technological, probiotic, spoilage, and/or pathogenic microorganisms occurring in fermented foods, as well as on the characterization, evolution, and metabolism of microbiota that occurs during the production, storage, and distribution of these products.This Special Issue of In their study, Hussain et al. examineddonejang, a fermented soybean product, using 29 samples originating from different regions of Korea. In particular, the biogenic amine content, bacterial composition, and metabolic functions were assessed.Jeong et al. investigFagbemigun et al. investigPediococcus acidilactici M76 for the lactic acid fermentation of black raspberry extract, whereas Thongwai et al. [Komagataeibacter maltaceti species, and characterized its ability to produce bacterial cellulose.Song et al. assessedi et al. identifiClostridium tyrobutyricum strains with different genotypic and proteotypic profiles, showing that strain-specific germination and growth characteristics should be considered among other factors to evaluate the risk of cheese spoilage by this spoilage agent of hard and semi-hard cheeses.Finally, Podrzaj et al. compared"} +{"text": "Incorrect AffiliationIn the published article, there was an error in affiliation(s) 1. Instead of \u201cThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, China\u201d, it should be \u201cDepartment of Radiology, Hainan Hospital of PLA General Hospital, Sanya, China\u201d.In the published article, there was an error in affiliation(s) 2. Instead of \u201cDepartment of Radiology, Hainan Hospital of Chinese PLA General Hospital, Sanya, China\u201d, it should be \u201cThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.Additional Affiliation(s)The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.In the published article, there was an error regarding the affiliation 1 for Xin Li and Zhiye Chen. As well as having affiliation(s) 1, they should also have The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The Oncologist, Volume 27, Issue 12, December 2022, Pages 1058\u20131066, https://doi.org/10.1093/oncolo/oyac188This is a correction to: Cara Mathews, Domenica Lorusso, Robert L Coleman, Susan Boklage, Jamie Garside, An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer, In the originally published version of this article, there were errors in the panels A and B of Figure 2: Dostarlimab should show a blue line and Doxorubicin should show a red line.This error has been corrected."} +{"text": "The lower consumption of NP1 and NP2 by postmenopausal women was associated with a higher risk of osteopenia, but not osteoporosis.Nutrient patterns (NPs) and the synergistic effect between nutrients have been shown to be associated with changes in bone mineral density (BMD). This study aimed to identify NPs and to associate them with BMD categories in postmenopausal women. This cross-sectional, observational, analytical study was carried out with women in menopause for at least 12 months, aged \u226550 years. Sociodemographic, lifestyle, and clinical variables were investigated. BMD was assessed using dual energy X-ray absorptiometry. A dietary assessment was conducted using a food frequency questionnaire, and three nutrient patterns were extracted from the principal component analysis. Multivariate logistic regression was applied to investigate the association between BMD classifications and NP consumption. A total of 124 women, aged on average, 66.8 \u00b1 6.1 years, were evaluated. Of these, 41.9% had osteopenia and 36.3% had osteoporosis. The NP1 (OR: 6.64, [CI95%: 1.56\u201328.16]; Skeletal disorders such as osteopenia and osteoporosis result from reduced bone mineral density (BMD) and the deterioration of bone microarchitecture ,2. OsteoIn addition to hormonal changes, several modifiable factors such as smoking, physical activity, and dietary factors are associated with BMD in postmenopausal women and with the possible deleterious outcomes in the bone health of this population ,8,9. SomThe relationship between NPs and BMD in older adults, especially postmenopausal women, has only recently received attention ,14,15,16Considering the heterogeneity of the results of previous studies and the lack of a conclusive NP to address BMD, it is necessary to clarify which patterns may be related to bone mass and the consequent development of disorders such as osteopenia and osteoporosis. Furthermore, by evaluating the consumption patterns of postmenopausal women and their correlation with the aforementioned outcomes, it may be possible to add new nutritional recommendations for the prevention and treatment of osteoporosis. In this sense, the aim of this study was to identify NPs and to associate them with the BMD categories of postmenopausal women.\u00ae Version 3.01, Atlanta, GA, USA) software ; p = 0.030, respectively) when compared with women in the third tertile. In the adjusted models, the first tertile of NP2 consumption remained associated with osteopenia, with an increased risk , while the second tertile lost its association with osteopenia when adjusting for PA level, antiresorptive drugs, and calcium and vitamin D supplementation. We found no association between the NPs and osteoporosis in the model presented (p > 0.05) .In the present study, NP1 was inversely associated with osteopenia. In other words, the lower consumption of this pattern increases the risk of postmenopausal women of having compromised BMD. This same association was observed for NP2, defined by a high consumption of iron, vegetable protein, thiamine, folate, total fiber, PUFA, insoluble fiber, vitamin A, vitamin K, alpha-tocopherol, copper, sodium, and retinol.The NP1 and NP2 identified in our study are composed of a large number of nutrients that are important for bone health; hence, their association with osteopenia. Bone is composed mainly of proteins, which, in addition to playing a structural role, have an anabolic effect via insulin-like growth factor 1 (IGF-1) . IGF-1 aThe role of other B-complex vitamins in bone health is still unclear, but there are indications that they are linked to homocysteine metabolism, which involves remethylation that is dependent on vitamin B12 and folic acid (B9), and trans-sulfuration that is dependent on vitamin B6 . EvidencAmong minerals, zinc and copper are essential cofactors for enzymes involved in bone matrix synthesis, acting to stimulate bone formation and to suppress its remodeling , with poFurthermore, fibers seem to increase intestinal calcium absorption in both rats and humans, and improve bone parameters ,66,67. INP3, characterized by a high consumption of carbohydrates, soluble fiber, total sugar, and vitamin C, while being low in total lipids, saturated fat, and MUFA, was not associated with osteopenia and osteoporosis. That may be due to the low number of nutrients correlated in this pattern, in addition to the absence of important nutrients for bone health , althougIn contrast to our initial hypothesis, no association was observed between NP and osteoporosis. The explanation for the lack of association may lie in the characteristics of the population studied. Of the 124 women evaluated, only 45 were classified as having osteoporosis, and their distribution between NP1 and NP2 was uniform, which may have caused the loss of effect on BMD. In addition, because of the characteristics of the study, this condition was previously established, and the women may have modified their consumption patterns because they were oriented on the importance of calcium, vitamin D, and other nutrients for bone health during outpatient treatment.2 increase in BMD [Our results are consistent with those from the few other studies available on the relationship between NP and BMD in postmenopausal women ,15. In ae in BMD . It is ne in BMD . FurtherThis study has some limitations, such as the cross-sectional design that does not allow us to infer the causality between the NP identified and osteopenia. There is a need for longitudinal studies, especially in this population, in order to clarify the relationship between nutrients in the development of osteopenia and osteoporosis. The use of drugs such as glucocorticoids, and other chronic diseases such as cancer, diabetes, chronic kidney diseases, and human immunodeficiency virus (HIV), which may increase the risk of osteoporosis, were not evaluated, which could be a confounding factor . The meaIn conclusion, a lower consumption of NP1 and NP2 was negatively associated with BMD. So, postmenopausal women in this study were at greater risk of osteopenia when they consumed less of the dietary pattern rich in vitamin B12, pantothenic acid, phosphorus, riboflavin, animal protein, total protein, vitamin B6, potassium, vitamin D, vitamin E, calcium, cholesterol, \u03b2-carotene, omega 3, magnesium, zinc, niacin, and selenium (NP1); or of those rich in iron, vegetable protein, thiamine, folate, total fiber, PUFA, insoluble fiber, vitamin A, vitamin K, alpha-tocopherol, copper, sodium, and retinol (NP2). The nutrients present in these patterns are characteristic of a diet that is rich in vegetables and milk and their derivatives, and they are related to bone metabolism, demonstrating the importance of nutrition with essential nutrients, especially calcium, phosphorus, magnesium, protein, and vitamin B12 for the maintenance of bone health. Further studies, especially longitudinal ones, are needed to confirm our results, especially with postmenopausal women, who may suffer more from the consequences of bone deterioration."} +{"text": "M = 14.46 \u00b1 1.883 years old). Using SPSS software, descriptive statistics were determined for all variables; mean differences between age and gender were found using ANOVA and the post hoc Scheffe test. Linear regressions with the Enter method were used to study how to predict perceived quality of life and satisfaction with life. Results: Males had scores indicating more SSES|optimism, emotional control, resilience, confidence, sociability, creativity, energy, a sense of belonging to school, and PYD. Girls had better skills for cooperating and relating to teachers but more test anxiety and DASS. Younger adolescents had better psychological health, greater skills, and a better perception of quality of life and life satisfaction when compared to older adolescents. Age, gender, SSES, PYD, and the DASS variables can explain 69% of the variance in life satisfaction, while these variables can explain 60.5% of the variance in perceived quality of life. Conclusions: These results point to the relevance of SSES for psychological health and well-being, suggesting that interventions should focus on promoting these variables, paying special attention to female gender and age-related challenges.Background: After two years of psychological, physical, social, economic, environmental, and societal challenges, this paper examines the psychological health and well-being of Portuguese students based on their socioemotional skills (SSES), positive youth development (PYD), depression, anxiety, and stress (DASS), as well as the relationship between these variables and their influence on perceived quality of life and life satisfaction. Methods: This study examined 3235 students from lower to upper secondary, half of whom were female ( The pandemic had a particularly negative impact on adolescent age groups\u2019 on physical and psychological health ,2, but aConsidering gender disparities, girls were the gender most impacted by the pandemic in terms of psychological health and well-being ,17,18, eWhen examining the various socio-emotional competencies, girls demonstrated greater ability, particularly in social awareness, pro-social behavior, and responsible decision-making, whereas boys demonstrated greater self-management ability and motivation . Taking From a positive developmental analysis perspective , the litA positive development is associated with the efficacy of mental health problem prevention practices ,27,28. PRavens-Sieberer et al. observedThe present study looks at the psychological health and well-being of Portuguese students based on their socio-emotional skills (SSES), positive youth development (PYD), depression, anxiety, and stress (DASS), as well as the relationship between these variables and their effects on perceived quality of life and life satisfaction.H1.\u00a0Gender differences exist for socio-emotional skills (SESS), positive youth development (PYD), depression, anxiety, and stress (DASS).H2.\u00a0Socio-emotional skills (SESS), positive youth development (PYD), and depression, anxiety, and stress (DASS) vary with age.H3.\u00a0There is a correlation between gender, age, socio-emotional skills (SESS), positive youth development (PYD), depression, anxiety, and stress.H4.\u00a0Gender, age, socioemotional skills (SSES), positive youth development (PYD), depression, anxiety, and stress (DASS) are predictors of perceived quality of life.H5.\u00a0Gender, age, socioemotional skills (SESS), positive youth development (PYD), depression, anxiety, and stress (DASS) all predict life satisfaction.With the answers to these hypotheses, we hope to contribute not only to the investigation of the current landscape of the psychological health and well-being of adolescents, which has been extensively studied, but also to the relationship between SSES, PYD, and DASS with perceived quality of life and life satisfaction, which we did not find to be extensively studied and which could be a key focus for the development or adaptation of health promotion interventions.In the study \u201cPsychological Health and Well-being|Observatory of Psychological Health and Well-being: Monitoring and Action\u201d, the Directorate-General for Education and Science Statistics, the Directorate-General for Education, the National Program for the Promotion of School Success, the Aventura Social Team/ISAMB/University of Lisbon, the Order of Portuguese Psychologists, and the Calouste Gulbenkian Foundation collaborated and approved all the instruments used. This investigation began in December 2021 with Ministry of Education approval.The sample consisted of a stratified and random selection of Portuguese mainland public schools by geographic region/NUTS III . In total, 27 groups of schools were included in which classes were also drawn, including all levels of education available in the school cluster . In February and March 2022, after stratified and random selection of each grade\u2019s classes, the liaison teachers and psychologists of the participating schools administered the data collection instruments in computer rooms. Students only completed online questionnaires with parental informed consent. The application protocol lasted between 20 and 30 min on average. Methods and outcomes are described in detail in the online study report that is M = 14.46 \u00b1 1.883 years) from lower secondary to upper secondary . In total, 46.1% of respondents were male, 50% were female, and 3.9% did not respond.This study included 3235 pupils aged 11 to 18 , examinePositive Youth Development , and homogeneity, which was not guaranteed in the majority of the variables, but was prioritized due to the similar number of cases in each subgroup and the robustness of the parametric tests in the face of violation.\u2192Starting with descriptive statistics for all variables under consideration, ANOVA tests were used to look at differences in means based on gender and level of education. The post hoc Scheffe test was used to control multiple comparisons whenever there were more than two conditions. This test was prioritized since it was intended to investigate all possible contrasts between the means of the groups and can be used when there is or is not an equality of cases in the groups. Using the Pearson test, a cross-sectional analysis was conducted to confirm the relationship between the variables under investigation and to ascertain their magnitude and effect. The correlational analysis and literature review bolstered the need for an in-depth examination of the variables gender, age, SSES, PYD, and DASS in predicting perceived quality of life and life satisfaction.\u2192Linear regressions were performed with the Enter method to assess the prediction of perceived quality of life and life satisfaction. The assumptions of the model, namely normal distribution, homogeneity, and error independence, were analyzed. The first two hypotheses were validated graphically, while the independence hypothesis was validated using the Durbin\u2013Watson test. VIF was utilized to identify multicollinearity. Every outlier was removed.\u2192The significance level was set at 0.05.In the analysis of gender-based mean differences in the scales and subscales SSES , perceived quality of life, life satisfaction, PYD (Positive Youth Development)|competence, confidence, and connection, and DASS |depression, anxiety and stress, statistically significant differences were found in the variables: SSES|optimism, emotional control, resilience/resistance, confidence, sociability, PYD = competence, confidence, and connection; DASS = depression, anxiety, and stress. No statistically significant differences existed between the dimensions of SSES|curiosity and persistence.The male gender showed a higher mean across all domains except SSES|cooperation, relationship with teachers, and test anxiety, DASS|depression, anxiety, and stress .In the study of academic year differences, all variables (except DASS|anxiety) exhibit statistically significant differences when comparing differences in means.Regarding lower secondary, the 7th grade has a higher average in the domains SSES|optimism, emotional control, resilience/resistance, confidence, curiosity, sociability, persistence/perseverance, creativity, energy, cooperation, self-control, sense of belonging to school, bullying, and relationships with teachers; PYD|competence, confidence, and connection; perceived quality of life and life satisfaction, in contrast to the 8th grade. The 8th grade has higher averages for DASS|stress and depression, with less favorable results.With a more positive outlook, the 7th grade only stands out negatively in terms of bullying, while the 9th grade has a lower result.However, in upper secondary, 10th graders have a higher average in the dimensions of optimism, emotional control, resilience/resistance, confidence, curiosity, sociability, persistence/perseverance, creativity, energy, cooperation, self-control, and a sense of belonging to school; PYD|competence, confidence, and connection; perceived quality of life and life satisfaction, compared to 12th graders. Year 12, excluding SSES|curiosity, persistence/perseverance, creativity, cooperation, self-control (11th grade), a sense of school belonging, and relationships with teachers. Year 11 has a higher mean for SSES | bullying and a lower mean for relationships with teachers than Year 12, which stands out favorably. In contrast to the 10th grade, the 12th grade has a higher average in the DASS|stress and depression.In the 8th grade, the means of all SSES dimensions (except test anxiety), PYD, perceived quality of life, and life satisfaction decrease, except DASS|stress and depression, which tend to rise. The dimensions SSES, PYD, and perceived quality of life tend to increase in the 9th grade, then again in the 10th grade, before decreasing in the 11th grade, and, in some cases, tending to decrease in the year that follows (12th grade). Bullying and test anxiety tend to increase in 11th grade.With an improved outlook in 7th grade, a decline in 8th grade, and an improvement in 9th grade, satisfaction with life tends to decline after 9th grade. DASS|stress and depression are also more positive in 7th grade, with an increase in 8th grade, an improvement in 9th grade, and successive increases in subsequent years .In the examination of variable correlations, a significant negative correlation was found between age and SSES|optimism, resilience/resistance, confidence, sociability, energy, sense of belonging to school, bullying, perceived quality of life, and life satisfaction; PYD|competence and connection, indicating that these domains tend to decline with age. Nonetheless, there is a significant positive correlation between age and SSES|cooperation, curiosity, and test anxiety, and DASS|depression and stress.No significant correlations existed between age and the variables SSES|emotional control; PYD|confidence; DASS|anxiety.Overall, significant positive correlations were found between all SSES subscales, suggesting that as one subscale increases, the others tend to increase as well, except bullying, which demonstrates a significant negative correlation with the other subscales. There is no significant correlation between test anxiety and curiosity and bullying, and there is a negative correlation between test anxiety and all subscales except cooperation and relationship with teachers.All variables except SSES|bullying and test anxiety and DASS|depression, anxiety, and stress are significantly and positively correlated with perceived quality of life and life satisfaction. This analysis suggests that as life satisfaction and perceived quality of life increase, so do SSES capabilities.PYD|competence correlates positively and significantly with all domains except age, bullying, test anxiety, and DASS dimensions. Except for the lack of a substantial correlation between age and PYD|confidence, the pattern holds for both PYD|confidence and connection.DASS|stress has a significant correlation with all variables, both positively and negatively, with age, bullying, test anxiety, and other DASS domains|depression and stress. The DASS|depression and anxiety (correlation with age is not significant), exhibit the same trend .A multiple linear regression (Enter method) was conducted using the variable age, gender, PYD, SSES, and DASS to determine the predictability of perceived quality of life after checking for and deleting outliers. Multicollinearity was not an issue as the VIF never exceeded 10 in any of the variables, and the tolerance never fell below. The data do not satisfy the assumption of independent errors . The histogram of standardized residuals and the normal P\u2013P plot of standardized residuals indicated that the error distribution of the data was approximately normal. The data also support the hypothesis of non-zero variances.F(23.2804) = 186.812. p \u02c2 0.001. R2 = 0.605. R2Adjusted = 0.602), indicating that the independent variables explain 60.5% of the variance in perceived quality of life , pointing to positive autocorrelation. The histogram of standardized residuals and the normal P\u2013P plot of standardized residuals indicated that the data contained approximately normally distributed errors. The data also met the assumption of non-zero variances.F(23.2802) = 110.879. p \u02c2 0.001. R2 = 0.69. R2Adjusted = 0.47) revealing that the total variation in life satisfaction can be explained by 69% by age, gender, and the variables SSES, PYD, and DASS (A multiple regression (Enter method) based on the previous set of independent variables but investigating their prediction of life satisfaction revealed a significant equation , positive youth development (PYD), and depression, anxiety, and stress symptoms (DASS). The results align with earlier studies that suggest that a person\u2019s ability to adjust to environmental challenges has an impact on their overall well-being and quality of life ,18,29. AGender differences exist for SSES, PYD, and DASS. Regarding gender, it was observed that SSES, DASS, PYD, perceived quality of life, and life satisfaction scores were lower for the female group in comparison to the male group. These findings are consistent with previous studies . The lowSSES, PYD, and DASS vary with age. Aging (measured by the school year proxy) was associated with lower levels of emotional health, optimism, resiliency, self-confidence, and sociability. Prior studies have shown a connection between advancing age, increased socioemotional skills deficits, and psychological symptoms , which lAs youth mature and approach maturity, the indicator of bullying tends to decrease. Consistent with the present study, the HBSC 2022 study in Portugal found that younger people were more likely to report being abusers or victims of bullying . SimilarIn our models, aging (measured by the school year proxy) was associated with a lower perception of life satisfaction, but not with perceived quality of life. Growing up implies maturation, but the results indicate a negative impact on the young person\u2019s socio-emotional state. Literature has shown that as individuals grow and develop, they are faced with increasingly complex and difficult challenges related to their personal and environmental circumstances. This can include academic pressure and family issues ,48. MakiIn adolescents\u2019 own words, when students are required to take entrance examinations for higher education in the twelfth grade, test anxiety tends to increase relative to other grades, possibly due to the increased importance of the exams. The difficulties associated with rising student development and school demands may help to explain the negative correlation between this variable and the majority of socioemotional skills. Similar results were found in a national study by Matos et al. analyzinAge is not a predictor of quality of life perception, unlike gender, SSES, PYD, and DASS. Age, SSES, PYD, and DASS can all predict life satisfaction, but gender is not one of them. According to our results, satisfaction with life is also impacted by SSES|optimism, sense of belonging to school, PYD|confidence, and connection. For their part, SSES|optimism, confidence, curiosity, energy, and PYD|connection reveal a favorable impact on the explanation of perceived quality of life. An interesting result from our perspective is the fact that SSES|bullying does not reveal a negative relationship with perceived quality of life, and in the literature, bullying shows a negative impact on health-related quality of life , or the Promote socio-emotional skills and literacy, adapting to the gender and years of schooling specifics identified here, e.g., proactive work;Increase (or acquisition) clinical psychologists in schools and health facilities, e.g., preventive work;Avoid reactive work, which is required in instances of moderate or severe symptomatology or pathology.It is crucial to understand that, in addition to their academic environment, adolescents\u2019 familial environment has a significant impact on their mental health. According to Matos et al.\u2019s study , adolescRegarding the study\u2019s strengths, it is important to note that it was conducted during the first school year after the return to the new post-COVID-19 normality, allowing us to see the actual situation and the psychological health requirements and characteristics of Portuguese students. In addition, the size of the sample and its stratification by the Portuguese mainland territories enable a country-wide perspective. Third, a period of development analysis between lower and upper secondary has different features. On the other hand, we note that the study is cross-sectional, we cannot be sure that the sample is representative, and we only used one method to collect data.In a subsequent study, in order to comprehend how the model behaves, a more in-depth examination will be conducted by education level and gender."} +{"text": "The use of selective serotonin reuptake inhibitors (SSRIs) has increased exponentially and worldwide in the last decade. Taking into account their tolerability and safety profile, they constitute the first line, in all age groups and in polimedicated population, for treatment of depressive, anxious, and phobic disorders, among others. Although safe, especially when compared to first generation antidepressants, they are not totally exempt of adverse effects, and may cause, especially in this context, some degree of cognitive impairment, which may or may not be completely reversible. On the other hand, and despite the controversy related to the subject, some studies suggest a possible protective effect of this pharmacologic class regard the development of cognitive disfunction, which, although not very consistent, should not be neglected.To understand the cognitive impact of short- and long-term use of SSRIs, given the increasing use in an aging, polymedicated population.SSRIs\u201d, \u201ccognitive\u201d, \u201cimpairment\u201d, \u201cadverse effects\u201d, \u201cdementia\u201d.Brief sistematic review of selected articles from Pubmed, Medline and Uptodate databases, with the keywords \u201cSSRIs are not entirely exempt from cognitive effects, despite their recognized safety profile. Some of the adverse effects typically related to the class, such as hyponatraemia, especially when insidious and silent course, as well as anticholinergic activity interfere with global functionality and may clinically present as mild cognitive impairment or even major neurocognitive disorders. Furthermore, given their potential to induce or inhibit the cytochrome P450 system, they are significantly implicated in pharmacokinetic drugs interactions that increase cognitive burden associated with other psychotropic drugs.In the long term, and in certain patient populations, it has been hypothesized that they may exert some protective effect on physiological and pathological cognitive functions decline, by preventing neuronal death, acetylcholine decrease and amoyloidogenesis.Despite their benign adverse effect profile, when compared with tricyclic antidepressants, SSRIs are not devoid of adverse effects on cognitive domains. However, and despite contradictory and inconsistent results, when well tolerated, SSRIs may confer benefits in terms of preserving global functionality, far beyond the affective symptoms resolution that motivated their introduction in the first place.None Declared"} +{"text": "Mental health issues can have significant impacts on individuals and communities and hence on social sustainability. There are several challenges facing mental health treatment; however, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring. This requires a holistic approach to understanding mental health issues that are missing from the existing research. Mental health should be understood in the context of social and environmental factors. More research and awareness are needed, as well as interventions to address root causes. The effectiveness and risks of medications should also be studied. This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters related to mental health from Twitter data. The parameters are discovered from three different perspectives: Drugs and Treatments, Causes and Effects, and Drug Abuse. We used Twitter to gather 1,048,575 tweets in Arabic about psychological health in Saudi Arabia. We built a big data machine learning software tool for this work. A total of 52 parameters were discovered for all three perspectives. We defined six macro-parameters to aggregate related parameters. We provide a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse, as seen on Twitter, discussed by the public and health professionals. Moreover, we identify their associations with different drugs. The work will open new directions for a social media-based identification of drug use and abuse for mental health, as well as other micro and macro factors related to mental health. The methodology can be extended to other diseases and provides a potential for discovering evidence for forensics toxicology from social and digital media. Several factors are contributing globally to declining social sustainability including people\u2019s health, economic issues, global events such as the COVID-19 pandemic and environmental disasters, and increased social division and polarization [Mental health is related to social sustainability because it is an important aspect of overall health and well-being, and mental health issues can have significant impacts on individuals and communities. Mental health issues such as depression and anxiety can lead to decreased productivity, absenteeism, suicides, and other negative impacts on social and economic well-being. For example, according to the World Health Organization (WHO), there is a suicide every 40 s, totaling more than 700,000 per year. This high rate of suicide highlights the deteriorating social conditions around the world .Moreover, addiction is often related to mental health in that it can be a symptom of, or a response to, underlying mental health issues. For example, people may turn to substances or behaviors such as drugs, smoking, alcohol, gambling, or internet use as a way to cope with mental health issues such as depression, anxiety, or stress. However, addiction can also contribute to, or exacerbate, mental health problems, as the use of substances or engagement in certain behaviors can have negative impacts on mental well-being . The CenThere are several challenges facing mental health treatment, including a lack of access to care, stigma, a shortage of mental health professionals, limited treatment options, co-occurring disorders, and a lack of integration with physical health care. These challenges can make it difficult for people to receive the mental health treatment they need, which can have negative impacts on their well-being and overall quality of life. Addressing these challenges is important for promoting mental health and improving the well-being of individuals and communities.However, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring, improve the effectiveness of treatment, and reduce the need for ongoing care. Root causes of mental health issues can include trauma, genetics, environmental factors, and physical health issues. A multifaceted approach that addresses social, economic, and environmental factors as well as individual needs is needed to remove the root causes of mental health issues effectively.There is a significant body of research on the relationship between physical and psychological health. Studies have explored the connection between mental stress and physical diseases such as cancer, lung disease, and kidney disease ,7,8, as A holistic approach to understanding mental health issues is missing from the existing research. What is needed is to understand mental health and illnesses in the context of socio-economic and environmental contexts, create awareness for the people of the causes and effects of mental illnesses, and develop interventions to bring social behaviors, lifestyle, and root cause changes.This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters (or factors) related to mental health from Twitter data. The parameters are discovered from three different perspectives Drugs and Treatments, Causes and Effects, and Drug Abuse. Moreover, we automatically discover associations between the parameters and drugs. We gathered from Twitter 1,048,575 tweets in Arabic about psychological health in Saudi Arabia during the month of October 2022. The tweets were retrieved using various keywords and hashtags related to mental health. We built a machine learning software tool for this work using different data sources. See for instance ,7,8,17. Discussing works that used machine-learning methods in studying topics related to mental health, for instance, Iram et al. utilizedSeveral studies have utilized Twitter data for studying psychological health. Zhang et al. developeRegarding research on mental health using Arabic Twitter data, we have found only a limited number of studies. Alabdulkreem proposedOur work differs from previous research studies from a variety of perspectives including its particular focus, the nature of the dataset , the software design (the pipeline and approach for machine learning), the innovative methodology of using AI for discovering parameters, and the innovative methodology and design of finding associations between parameters and drugs.In this section, our methodology and the design of our tool are explained. Note that we have used contextual translations and made some adjustments to the translations of original Arabic tweets in order to make them more understandable to English readers. This may include changes to the order of the information in the tweet, the removal of unnecessary or redundant information, and the provision of summaries for tweets that are too long or contain unnecessary information. We have also sometimes omitted parts of the original tweets in order to protect the privacy of the tweeters. Note that Arabic tweets tend to be written in an informal style, so a literal translation may not always be clear or convey the intended meaning. Note also that in some tables in the paper, some search terms, or key terms detected by our machine learning models, may appear multiple times. This is because the original terms in Arabic may be different, but their English translations may be identical. The Arabic content is not presented in this paper due to the publisher\u2019s requirements. It can be found in an extended version of this paper made available on a preprint server .This study proposes a big data and machine learning-based approach for the automatic discovery of parameters related to psychological health from Twitter data. The proposed approach focuses on psychological disorders in Saudi Arabia but can be applied to other diseases and languages. There are five components in the proposed approach: data collection and storage, data preprocessing, drugs for psychological health parameters discovery, validation, and visualization and reporting. The first step was to use a Python script with a specified search query and a set of keywords and Twitter hashtags related to psychological health in Saudi Arabia. A discovery module was then constructed for data analysis and detection of parameters using Latent Dirichlet Allocation (LDA) and the scikit-learn library. We discovered the parameters from three different perspectives . The results for each perspective are discussed in detail in We collected Arabic tweets that are related to psychological health in Saudi Arabia using Twitter REST API and Tweepy. The data was obtained using various key terms and hashtags related to psychological health. For instance, the following key terms were used: depression, sadness, panic, mental illness, and others. Additionally, we used various hashtags such as depression month, social anxiety, social phobia, and others. A sample of the keywords used for data collection is as follows: suicide, social phobia, depression, depressed, sadness, fear, anxiety, obsessive, incantation, envy, panic, neurology, psychotherapy, mental health, psychological counseling, and mental illness. Some of the hashtags used include World Suicide Prevention Day, Suicide Awareness Month, suicide prevention, social anxiety, social phobia, depression, depression month, and seasonal depression. The list of Arabic key terms used in data collection can be found in an extended preprint version of this paper . The datData analytics requires the preparation of data as a critical ingredient. Data preprocessing involves a number of methods for cleaning, eliminating noise, improving quality, and, eventually, increasing accuracy. One of the libraries available for preparing textually based data is Natural Language Toolkit (NLTK). Preprocessing includes a number of steps including tokenization, normalization (replacing letters), stop word removal, and the elimination of irrelevant words and characters. Our first step in the preprocessing was eliminating all irrelevant characters and words such as numbers, URLs, different symbols , English alphabets, emojis, etc. Moreover, we eliminated non-Arabic characters, repeating characters, and all various forms of punctuation symbols such as brackets and mathematical notations. The next step was tokenization and normalization in which we removed all different types of Arabic diacritics including single marks such as Fatha, Dammah, Kasra, Tashdid, and Sukun as well as double marks such as Tanwin Damm, Tanwin Kasr, and Tanwin Fath. Moreover, we used the normalizer to convert all different shapes of Alif, Yaa, and Taa Murbutah to the basic form bare Alif, dotless Yaa, and Haa, respectively. After that, we removed the list of stop words provided by the NLTK library with an additional list of words in dialectical Arabic developed by us; further details of data-preprocessing of Arabic tweets including a list of Arabic stop words can be found in our earlier work .In this section, we discuss the methodology for identifying psychological health parameters through topic modeling analysis of Twitter data. Modeling of topics is a frequently employed AI approach for data analysis and topic discovery, and it contains various algorithms that identify patterns and themes in a collection of documents by clustering word terms . For topWe modeled the data from three perspectives: Drugs and Treatments, Causes and Effects, and Drug Abuse. We used a list of keywords to create a subset of the dataset and discover the parameters for each perspective. For instance, for the Drugs and Treatments perspective, we used names of antidepressants, painkillers, and medicines . For the Causes and Effects perspective, we used multiple keywords such as side, effects, and cause. For the Drug Abuse perspective, we used multiple keywords such as abuse and extra. Most of the keywords are in Arabic and few in English because some tweets use some terms in English such as medicine names. We modeled each perspective into different clusters. After extracting the clusters, we allocated each tweet to its cluster based on the highest probability of the tweet association with a cluster. After that, we performed an analysis of the tweets and keywords in each cluster in which we looked at the keywords and examined the context of the keywords in each parameter. This enabled us to name each cluster based on the keywords and tweets using our domain knowledge. We iteratively refined clusters\u2019 names using our domain knowledge and other quantitative measures. The process enabled us to eliminate irrelevant clusters and combine clusters that were similar. We eventually aggregated the parameters based on their common themes into macro-parameters that represent broader areas. This is done separately for each perspective.The discovered parameters were validated internally and externally. For external validation of the data and parameters extracted from the Twitter data, we utilized academic papers, news articles, and online reports. To assess the validity of the discovered data and parameters, internal validation was carried out utilizing tweets from the gathered dataset.In this study, we provide a variety of visualization methods of the parameters we have discovered. These are intertopic distance maps, taxonomies, and keyword frequency diagrams (both cluster-specific and corpus-wide). Python pyLDAvis package was used to compute and depict the terms frequency diagrams and distance maps ,51. The This section focuses on the parameters discovered for the Drugs and Treatments perspective. As noted in the Introduction Section, we have translated the Arabic content (words and tweets) contextually and made adjustments to the original text, including changes to the information order and the removal of unnecessary or redundant information. We have also omitted parts of the original text that were not useful.We used a list of Arabic and English keywords to create a subset of the dataset and discover the parameters for the Drugs and Treatments perspective. The subset contains 6717 tweets. The LDA algorithm detected 30 clusters from the subset of the dataset. We merged similar clusters, discovered parameters, and categorized them into five macro-parameters.The keywords used (translated into English) are as follows: medicine, drugs, pharmaceutical, medicinal, prescribe, prescription, dose, antidepressant, as anti (depression), anti (depressants), tranquilizer, milligrams, pill, pills, reliever, melatonin, Panadol, Rufenac, Celebrex, Ibuprofen, Acetaminophen, Brintellix, Duloxetine, Faverin, Seroxat, Lyrica, Remeron, Cipralex, Xanax, Benzodiazepine, Valium, Escitalopram, Leponex, Paroxetine, Bupropion, Imipramine, Haloperidol, Reserpine, Tetrabenazine, Clonazepam, Lorazepam, Diazepam, Amitriptyline, Nortriptyline, Mirzagen, Prozac, Serotonin, Cyproheptadine, Salipax, Tramadol, Wellbutrin, Letrozole, Cabergoline, Tranylcypromine, Gomood, Rhodiola, Ashwagandha, Duspatalin, and Omeprazole.A taxonomy see illustraIn this section, we discuss the parameters related to the macro-parameter Diseases and Disorders. This parameter is about postpartum depression which is a form of depression that develops in women after giving birth to a child. The parameter is represented by keywords such as depression, birth, gloom, death, mother, afflict, women, sadness, husband, hate, and postpartum. Several tweets in this parameter discuss the symptoms of this disease such as exhaustion and lack of energy, sleep disturbance, anorexia disorder, weakness in concentration, and thinking about death.In this section, we discuss the parameters related to the macro-parameter Individual Factors including anxiety, sadness, poor concentration, poor memory, loss of appetite, and fear of medicine. This parameter relates to anxiety, a common emotion characterized by worry, nervousness, and unease about an uncertain outcome. It is a normal reaction to stress that everyone experiences at some point, but anxiety disorders are more than short-term worries or fears. Anxiety can have a negative impact on daily activities such as work, school, and interpersonal relationships . Common This parameter relates to sadness. It includes the following keywords: depression, treatment, sadness, time, psychological, anti (depression), symptoms, psychological, pills, treatment, deep, disappointed, hopes, wound, and heal. Many tweets in this parameter initiate sad thoughts. Some of the tweets are poems. We found several tweets that contain poems focusing on sadness due to love. They initiate sad thoughts in people; although people may enjoy it first, it can lead to severe depression and suicide like any other intoxication. It is well known that sad songs may give enjoyment to lovers, but they may also become a source of depression.The poor concentration parameter regards the difficulties in concentration and the issues related to it. This parameter contains the following keywords: depression, medication, treatment, disorder, anti (depression), self, causes, pills, diabetes, deficiency, anxiety, prescription, treatment, psychological, and dangerous. Although these keywords do not directly mention concentration, they are about diseases related to concentration. Most of the tweets are about causes of poor concentration including depression and anxiety.The poor memory parameter discusses the negative effects of depression on memory and focus. People and experts discussed how depression affects memory and one\u2019s ability to concentrate and remember. Moreover, some tweets have highlighted that some people fear using antidepressants because they think that it will cause issues with memory and concentration.This parameter is about loss of appetite, which can happen because of depression. Some of the keywords in this parameter are biscuits, psychological, treatment, medication, depression, eating, taking, alone, light, coffee, chocolate, and food. Some people have mentioned loss of appetite among the negative effects of antidepressants.This parameter regards fear of medicine. Individuals with this fear may feel intense fear and worry when considering taking medication or going to a doctor or hospital. The parameter covers some factors of fear, including the length of medicine (duration of treatment), side effects, fear about taking the incorrect medication, worry about being incorrectly diagnosed, concern about becoming dependent on medication, and fear about medical procedures or treatments.Here, we cover the parameters related to the macro-parameter Social and Economic Factors including poverty, unemployment and insufficient finances, high cost of healthcare, loss of loved ones, forensic psychiatry, and social depression. This parameter relates to poverty as an economic factor that can cause mental health issues. This parameter captures various dimensions such as low household income, medical care, children, stealing, sadness, fear, depression, and psychological diseases. Some tweets under this parameter have highlighted how stealing money from poor people can have a devastating impact on their mental health. It can have a disastrous effect on the livelihoods of those affected, depriving them of the basic necessities such as food, shelter, and medical care that their families and children require for survival. Eventually, it can lead to feelings of despair, depression, and mistrust in others.This parameter discusses inadequate finances and unemployment as social and economic factors for depression and mental health issues. This parameter includes various dimensions detected by our model such as work conditions, unemployment status, children, prison, depression, and committing suicide.This parameter relates to the high cost of healthcare as one of the socioeconomic causes of depression. This parameter involves various dimensions such as low income; healthcare expenses; chronic diseases; healthcare expenses for elderly parents; and stress and pressure. Some tweets discussed how low-income elderly people with chronic illnesses, such as diabetes or hypertension, tend to incur greater expenses for medical services. This may result in inadequate housing and nutrition, which may worsen health outcomes. All of these factors may lead to higher healthcare costs for those who are poor. This can contribute to feelings of stress and pressure.This parameter highlights one of the social causes of depression, the loss of loved ones. The parameter is represented by keywords such as pills, depression, period, feeling, lost, most important, depression, best, sleep, matter, medicine, even, life, living, death, friend, desire, and Iniesta. Some tweets related to the depression experience of the football player Iniesta who got depressed from the death of his close friend. The following tweet is an example: \u201cWhen I was fighting depression, my best time was when I swallowed pills and went to sleep. Even hugging my wife was like hugging a pillow, without feeling.\u201d.This parameter is about forensic psychiatry, defined as \u201cthe branch of psychiatry that deals with issues arising in the interface between psychiatry and the law, and with the flow of mentally disordered offenders along a continuum of social systems\u201d . It is \u201cThis parameter is about social depression. This parameter highlights various dimensions such as stressful life events, stigmatization of medicines, weight increase, and lifestyle. This parameter emphasizes the fact that society is living in a time when the cost of living and healthcare has increased, and high achievement has become a necessity leading to social depression and anxiety.The parameters associated with Treatment Options macro-parameter are discussed in this section. This parameter discusses walking as a treatment for psychological diseases. It is represented by keywords such as prescribe, body, walking, negativity, psychological, energy, nature, anxiety, needs, medications, diseases, fear, equivalent, work, painkillers, emptying, endorphins, sedatives, and reduce. The tweets in this parameter discuss a range of benefits of walking such as triggering the body\u2019s whole muscular system and reducing relapses of mental illnesses.This parameter is regarding optimism, which is a psychological approach or outlook that emphasizes the beneficial aspects of life and anticipates positive results. Optimism is often regarded as a form of resilience, allowing individuals to manage challenging circumstances and recover from adversity . This paThis parameter is about good company and the importance of good friends for mental health issues. Some of the keywords for the parameter are depression, anti (depression), best, friend, anti (depressants), normal, good, and defect. People discussed how good friend can be as an antidepressant for depression. There are many tweets in this parameter such as the following, \u201cBest antidepressant: (a good) Friend\u201d.This parameter focuses on the pendulum technique. It contains the following keywords: fear, then, question, pendulum, yourself, effectiveness, know, answer, write, ask, feelings, attachment, ready, mention, answer, sharp, intention, depression, anti (depressants), and sun. It was detected as a treatment for psychological issues.This parameter covers spirituality as a treatment for sadness and depression. People discussed how spirituality is used to treat people from sadness and depression. For example, doing good actions, remembering God, and praying the morning prayer.The antioxidants parameter focuses on the role of antioxidants in fighting depression and mental illnesses. It is represented by key terms such as coffee, psychological, depression, oxidation, treatment, anti (depression), condition, people, helps, most, moods, relieve, improve, anti (oxidants), richness, fruits, combined, plus, and vegetables. The tweets in this parameter have discussed natural sources of antioxidants. Moreover, many tweets have mentioned how coffee is rich in antioxidants and how it can help relieve depression and improve mood state.The painkillers and antidepressants parameter highlights the difference between painkillers and antidepressants in terms of their use. This parameter contains the following keywords: depression, medications, disease, treatment, patient, psychiatric, medication, psychological, anti (depression), instead of, doctor, depression, for a patient, Cipralex, painkiller, body, give, Celebrex, and hurt. Some tweets have mentioned that antidepressants can be prescribed for physical illnesses. It is not clear from the tweets why an antidepressant is prescribed. Doctors may see some symptoms of depression.This parameter is about community-supported therapies. This parameter includes various dimensions such as community support groups, society programs, faith, successful treatment factors, etc. Here is an example of a related tweet: \u201cPsychological diseases involve a set of genetic, familial and social factors, and therefore recovery from them also requires a combination of all these factors, such as regular use of medication, adherence to healthy habits and lifestyle \u201csports\u201d, family support, community awareness and embrace and not to reject those who suffer from it, or to stigmatize them as weak or lacking in faith!\u201d.This parameter is about the types of medical treatments for psychological illnesses, which are Cogitative Behavioral Therapy (CBT) and the use of medications/drugs. A number of tweets discuss psychotherapy and medication. For example, a tweet stated that \u201cin mental illness, each case is different from the other. And depends on the condition and depression degrees. Medicines are used in severe cases and behavioral therapy benefits most people. Therefore, first, you must visit a doctor, who will examine you and let you know whether you need to take medicine or undergo behavioral therapy\u201d. In addition, some tweets highlighted the importance of lifestyle for mental health.The parameters related to the macro-parameter Treatment Limitations are covered in this section. This parameter discusses antidepressant limitations. It is represented by keywords including depression, medicine, truth, relieve, reality, natural, dealing, mind, crises, right, exaggerating, delight, emotion, happiness, nervousness, etc.The parameter is about the negative effects of antidepressants. It is represented by keywords such as depression, medicine, anti (depressants), people, psychological, sadness, possible, pill, condition, psychological, actually, disease, nervousness, causes, etc. There are many tweets that mention the side effects of antidepressants. As previously noted, we have translated the Arabic content (words and tweets) contextually and made adjustments to the original text, including changes to the information order and the removal of unnecessary or redundant information. We have also omitted parts of the original text that were not useful. Here is an example tweet: \u201cIf the psychiatrist is incompetent, he will give the patient pills that ruin a person\u2019s life\u201d. A tweeter stated that one of her siblings committed suicide after a doctor convinced him that his depression doesn\u2019t have a solution and there is no treatment for it. In addition, in another case, it was reported in a tweet that someone\u2019s close relative was prescribed so many strong pills that if he forgot to take them for a day or two he would have a bout of screaming and crying.A number of tweets mentioned some diseases that were detected by our tool as side effects of antidepressants such as obesity, drowsiness, bruxism, and attention-deficit/hyperactivity disorder (ADHD). Some tweets have discussed the positive sides of using antidepressants. For example, the following tweet: \u201c\u2026 some mental illnesses are chronic like some physical illnesses such as diabetes and high blood pressure. Therefore, you may need to take antidepressants for long periods or all of your life\u201d. Several tweets have mentioned other ways of treating depression such as electroconvulsive therapy (ECT), St. John\u2019s wort, and magnesium.In this section, we provide the associations between the detected parameters and drugs for the Drugs and Treatments perspective. These are shown in These parameter-drug associations can be discovered automatically as follows: we built a vocabulary of all medicines used for the treatment of psychological illnesses, and we searched for these medicines against tweets in each parameter and recorded the associations with the drugs found through the search for each parameter.This section discusses the parameters discovered for the Causes and Effects perspective. An overview of parameters and macro-parameters is provided in We created a list of Arabic keywords to build a subset of the dataset and identify the parameters for the Causes and Effects perspective. The dataset obtained contains 88,566 tweets. The parameters and other information on the Causes and Effects perspective are provided in The keywords employed are side, effects, because of, cause it, it causes, caused by, cause, brought, result, weight, my weight, cholesterol, disorders, lethargy, migraine, appetite, metabolism, memory, concentration, dizziness, sleep, insomnia, headache, crying, stomach, hyperactivity, attention, deficit, depression, and addiction.In this section, the parameters that belong to the macro-parameter Diseases and Disorders are discussed including attachment disorder, insomnia, and obsessive-compulsive disorder (OCD). This parameter is about attachment disorder, which is a form of mental illness or behavioral condition that interferes with a person\u2019s capacity to establish and sustain relationships. It relates to the challenges involved in understanding emotions, expressing affection, and placing one\u2019s trust in others. The parameter is represented by keywords such as psychological, health, family, live, your life, hospital, person, reality, well-being, success, locked up, lost, attachment, money, etc. People discussed that someone should avoid excessive attachment to loved ones as it can destroy person\u2019s life. Furthermore, a case of a celebrity who was deceived by a loved one was discussed.This parameter focuses on insomnia, which can be a cause or an effect of other psychological issues. This parameter is characterized by keywords such as sleep, sadness, anxiety, doctor, eye, fear, depression, symptoms, fear, diaspora, matter, etc. People discussed different reasons for insomnia such as excessive worry, fear, depression, anxiety about events or people, sadness, excessive thinking, exhaustion, or loss and nostalgia.This parameter regards obsessive-compulsive disorder (OCD), which is a prevalent mental health problem characterized by compulsive behaviors and obsessive thoughts. People discussed the symptoms of OCD, the causes and treatment. For example, someone tweeted: \u201cObsessive-compulsive disorder is the control of an idea that its owner knows is absurd, forcing him to repeat actions, such as making sure the door is locked, cleanliness, or purity, to a degree that may affect the productivity of the individual. This indicates underlying anxiety and can be treated with some medication and dialogue...\u201d.This cluster is about post-surgery depression, and it focuses on surgeries as a cause of depression. The tweets associated with this parameter are mostly related to the depression that occurs after Sleeve gastrectomy surgery because the stomach is restricted to a certain food, and this has a negative effect, such as feeling lonely or that the person cannot go out and eat a variety of foods like before. However, depression can happen as a side effect of any other surgery.The chronic physiological diseases parameter discusses various diseases that could lead to depression. The following keywords were detected by our model: depression, depression, cause, psychological, sick, chronic, king, medical, brain, fear, diseases, Salman, suffering, surgical, cause, city, relationship, psychological, nerves, and compensate. When a person suffers from a disease that affects his ability to move and could lead to some changes in lifestyle, this could result in depression. A tweet mentioned five chronic diseases which cause depression and sadness including diabetes mellitus, arthritis, heart disease, kidney failure, and thyroid gland. Some other tweets linked COVID-19 infection to a range of chronic neuropsychiatric disorders, including depression, memory problems, and Parkinson\u2019s disease-like disorders.We highlight here the parameters under the macro-parameter Individual Factors. There are eight parameters. This parameter is about fear as a cause or effect of psychological illnesses. Our model detected the following keywords: leave, care, fear, weight, gain, about you, subject, sleep, diseases, poverty, keep away, think, difference, fear, doctor, health, face, your fear, and sources. The tweets highlighted different kinds of fear including fear of losing persons, fear of diseases, fear of poverty, and others.This parameter is about sadness which could be a symptom, a cause, or an effect of psychological diseases. It is represented by keywords including world, depression, wish, real, people, complete, me, normal, age, try, need, needs, work, fear, person, years, time, stay, etc. This parameter is similar to a parameter covered in the previous perspective. For more details see This parameter is about loneliness, which is characterized by keywords such as wish, heart, alone, sadness, complete, pass, loneliness, mind, stage, fear, focus, nights, human, thinking, anxiety, unknown, details, compensate, trust, and calm down. Someone tweeted: \u201cI hope that God will compensate me for all the nights of loneliness, sadness and misery, and reassure my heart \u2026\u201d.This parameter is about people who lost their sense of value and pleasure in everything and wish for death. This parameter includes the following keywords: depression, want, need, myself, times, moment, desire, overwhelming, disappear, the world, have, presence, heavy, exist, feel, want, depression, sadness, and view. People discussed different symptoms associated with lacking passion such as a feeling of helplessness, low energy and exhaustion, constant pain, and the feeling of guilt. Other tweets have mentioned other symptoms including a lack of self-esteem, self-loathing, lack of focus, loss of hope, and the desire to disappear.This parameter is about the suppression of emotions either positive or negative, which can lead to depression and other psychological illnesses. Based on our model, the following keywords were detected: sadness, sorrow, physical, cause, after, able, personality, disease, experience, sleep, possible, upset/angry, need, your chest, was not, wish, tell, say, inside, and live. Some tweets highlighted some of the effects of suppressed emotions such as anxiety, depression, and other stress-related illnesses. Other tweets mentioned the importance of discussion and expressing emotions for psychological health.The negative emotions parameter is about people who talk about and share their personal negative experiences and generalize them, causing depression for themselves and others in society. It is represented by keywords such as depression, condition, people, friendliness, because, human, life, depression, psychological, crying, sleep, conversation, life, yourself, have, sadness, anxiety, permanent, phrase, and love.This parameter regards the devil and negative thoughts. It is characterized by keywords such as most important, sadness, anxiety, whirlpool, fear, heart, devil, life, comfortable, bad, sorrows, stable, caused, current, last, past, make, tense, and destroy. People discussed how the devil negatively affects people\u2019s mental health. The following tweet is an example: \u201cRemember that one of devil\u2019s most important goals is to cultivate sadness and fear in the heart, so that he does not make you stable or comfortable, but rather discontented, anxious, and pessimistic. He links you to the past, its pains, and the sorrows it causes you, and links you to the future, its fears and anxieties; To make you always in a tense spiral and mistrust, and his goal is to destroy your current moment and spoil your life.\u201d.This parameter is about lacking inner peace. The following keywords were detected by our model: life, peace, anxiety, insomnia, stay away, in you, people, many, things, topic, anger, inside me, focus, your Lord, struggle, urgency, fear, anxiety, psychological, and joy. This parameter focuses on the importance of inner peace for fighting depression. People discussed different things such as how to get inner peace by avoiding passing judgment on people. Following is an example tweet: \u201cIf you do not feel peace within you, you will find many things in life that cause you anger, chaos, grumbling, anxiety, and conflict. How do I find peace inside me? get closer to your Lord; avoid passing judgment on people; stay away from focusing on any disturbing topic; live life with grace, not with complexity.\u201d.There are five parameters under the Social and Economic Factors macro-parameter. This parameter covers various study-related issues which could cause psychological illnesses such as studying for long hours, studies-related depression, and bullying in schools. The parameter contains the following keywords: concern, problem, subject, permission, fear, cause, psychological, lead, schools, academic, level, impact, delay, space, going, coming, elite, to school, disability, and counsellors. The tweets discussed the causes of psychological illness. For instance, the following tweet highlights different causes of psychological illnesses and some solutions which don\u2019t lie in drugs: \u201cWhen the psychologist\u2019s tweets highlight how some psychological disorders, such as depression, anxiety, etc., develop as a result of people\u2019s exposure to psychological trauma, abused childhood, or some social problems such as divorce and others. It is natural to find that the solution to these problems does not lie in drug treatment\u201d.Furthermore, a tweet stated a list of disorders which are related to certain causes. These disorders include anxiety disorders, especially panic attacks and anxiety about disease, depression and mood disorders, traumatic disorders, personality disorders, dissociative disorders, and internal psychological struggle due to social pressure. Another tweet highlighted various socioeconomic causes of depression and psychiatric disturbances. A tweet reported that \u201cthe poor economic state of the family may cause social problems and bad psychological effects that lead to excessive thinking and eventually lead to mental illnesses\u201d.A number of tweets reported that universities and schools cause fear and depression. Moreover, several tweets discussed the issues of bullying in schools and how it affects the academic progress of students. For example, a tweet mentioned that bullying in schools can cause depression, anxiety, social shyness, social phobia, and eventually delay in the academic level.This parameter focuses on work as a cause of psychological issues. Among the keywords that our model detected are depression, limit, need, possible, permanence, depressed, length, fear, offender, no one, praise be to God, literally, still, life, sufficiency, society, coming, and deficiency. People discussed how long working hours affect mental health and how leaving very little time for family and social relationships can result in depression and family breakup.This parameter is about the lifestyle as a cause of psychological illness including eating and thinking patterns. The parameter is represented by keywords such as time, depression, sadness, cause, grace, speech, problems, know, silence, understood, inside, pretended, stupid, committed, smiled, answered, wellness, weight, in relation to, and hospital. Here are some example tweets about maintaining a good lifestyle. For example, the following tweet: \u201cMost people write about pain and talk about fatigue until their minds are programmed to be depressed and think negatively which cause them illnesses\u201d.Following is another example tweet: \u201cMalnutrition is the cause of mental illness, which can be treated with diet, exercise, cupping, and good company rather than medicine. The consumption of indomie, soft drinks, and drinks containing stimulants causes fear. Alcohol, smoking, and sweets cause anxiety and depression.\u201d.This parameter is about the high cost of healthcare as a socioeconomic factor for psychological illnesses. This parameter includes the keywords depression, knew, make, have, session, psychological, period, good, for depression, seasons, diseases, suffering, fear, difficult, home, street, family, and life. This parameter is similar to a parameter covered in the previous dimension. For further details see This parameter is about seasonal depression which is a type of depression that occurs as a result of the change of seasons. This parameter is represented by keywords such as depression, Saturday, gloom, depression, severe, I have, birth, feel, winter, weather, spray, period, know, month, offender, people, cause, feel, atmosphere, and inside. In tweets and keywords, different types of depression were mentioned such as post-weekend depression, postpartum depression, and winter depression.This parameter regards emotional release (catharsis) as part of psychotherapy. The following keywords were detected by our model: depression, life, fear, hair, remove, cut, winter, sleep, name, family, wake up, satiate, inside, side, entered, smell, bring, come, answer, and people. Many tweets have talked about cutting hair as a way of emotional release. The following tweet, for example: \u201cCutting hair removes 100% of life\u2019s depression\u201d.This parameter is about good friends and is described by the following keywords: depression, better, anxiety, person, can, deeper, seriously, kidding, inside you, collect, spontaneity, quest, reach, continuity, wonderful, include you, the two things, the mother, cause, and not happened. People discussed the importance of good friends for psychological health. Following is an example tweet: \u201cWhen you talk to good friend while you are in a state of anxiety and fear, you become reassured because of his deep words and great actions\u201d.This parameter covers spirituality as a treatment for psychological illnesses. This parameter is similar to a parameter covered in the previous perspective. For further details see This parameter is about surgery as a treatment for psychological diseases. Among the keywords that our model detected are operation, depression, sadness, hours, surgery, success, suffering, future, sleep, psychological, medical, patient, mood, Salman, natural, first, thinking, anxiety, excess, and permanent. Several tweets have talked about the success of a surgical operation to treat a patient suffering from chronic depression.Similar to Furthermore, we found that some painkillers, such as Panadol, are associated with the Insomnia parameter. The research highlights that the use of painkillers may be associated with an increased risk of developing insomnia. Opioid use is likely to be a contributing factor to insomnia due to the sedative effects of opioids, which can make it difficult to fall asleep and stay asleep . FurtherIt is possible that individuals who experience pain or headaches and have difficulty sleeping may benefit from the use of painkillers. Research has demonstrated that individuals suffering from chronic pain often experience sleep disturbances , includiIn this section, we discuss the parameters discovered for the Drug Abuse perspective. An overview of parameters and macro-parameters is provided in In this section, we discuss the Drug Abuse perspective. We employed a list of keywords to build a subset of the dataset and identify the parameters for the Drug Abuse perspective. The following is a translation of the list of keywords utilized: abuse, mood, trance, without a recipe, pill, and extra. The dataset that we got after filtering data contains 2,701 tweets.The LDA algorithm detected 30 clusters for the Drug Abuse perspective. We excluded twenty clusters from the results as they were irrelevant to the focus of this perspective. We merged similar clusters, discovered parameters, and categorized them into five macro-parameters. Using the discovered parameters for Drug Abuse perspective, a taxonomy was created see .In this section, we discuss the parameters related to the macro-parameter Drug Abuse. This parameter relates to bipolar disorder, known as manic depression, which is defined as \u201ca mental illness that causes unusual shifts in a person\u2019s mood, energy, activity levels, concentration, and ability to carry out day-to-day tasks\u201d . It invoThis parameter regards university exams and is described by the following keywords: depression, condition, fine, pills, work, tried, unfortunately, help, peace, family, suicide, prison, answer, mercy, cut, tired, have, difficult, and see.This parameter relates to the death of loved ones as a cause of drug abuse. The following keywords were detected by our model: pills, depression, matter, feeling, period, depression, life, better, more important, medicine, even, death, lived, lost, sleep, go, desire, resistance, Kharkhi, etc. Some tweets relate to the depression of football player Iniesta and the death of his close friend which caused him depression.This parameter discusses addiction, known as substance use disorder. It is a condition characterized by an impaired ability to control the use of legal or illicit drugs, alcohol, nicotine, or other substances, resulting in changes in brain function and behavior . This paThis parameter is about abusing drugs and committing suicide as an effect of psychological issues. The following keywords were detected by our model: psychological, potion, treatment, heart, one, long, love, doctor, take, pass, fear, depression, bad, etc. Some people mentioned that they have tried to commit suicide by using an overdose of medicine.This parameter is about the Flakka drug. The following keywords were detected by our model: depression, fear, love, potion, intensity, newness, intake, feeling, problem, desire, alone, therefore, withdrawal, dope, lethargy, drug, to withdraw, attempt, symptoms, and depression. Many tweets mentioned that this drug is spread among young people and the reason for its spread is that it is cheap. People have also discussed the effects of using the Flakka drug such as hallucinations, madness, strange behavior, loss of control over mental abilities, and a mad start to a dark path. Many tweets have also mentioned the withdrawal symptoms of the drug such as feeling lethargy and suffering severe depression.This section highlights the associations between the detected parameters and drugs for the Drug Abuse perspective. In this research, we proposed a big data and machine learning-based approach for the automatic discovery of parameters related to psychological health from Twitter data. The parameters are discovered from three different perspectives: Drugs and Treatments, Causes and Effects, and Drug Abuse. Moreover, we automatically discovered associations between the parameters and drugs. The parameters were discussed in detail in We discovered twenty-four parameters from the Drugs and Treatments perspective and grouped them into five macro-parameters: Diseases and Disorders, Individual Factors, Social and Economic Factors, Treatment Options, and Treatment Limitations. A total of twenty-two parameters were detected from the Causes and Effects perspective and we grouped them into four macro-parameters: Diseases and Disorders, Individual Factors, Social and Economic Factors, and Treatment Options. We detected six parameters from Drug Abuse perspective, namely, bipolar disorder, university exams, death of loved ones, addiction, suicide, and flakka drug.A multi-perspective view of psychological health data is depicted in This work makes important theoretical and practical contributions to the area. The earlier research see has lookThis work sheds new light on the social and environmental factors that impact mental health and makes significant contributions to the field of toxics. Through the use of big data and machine learning, the study was able to identify the root causes of mental health issues from Twitter data and analyze parameters related to drugs and treatments, causes and effects, and drug abuse. As a result, this work provides a more comprehensive understanding of the complex social and environmental factors that contribute to mental health issues. This research seeks to identify and address the harmful social and environmental factors that can cause or worsen mental health issues, making it an important contribution to the field of toxics. Furthermore, it provides valuable insights into the relationship between mental health and various factors, which has the potential to inform the development of effective interventions that can improve public health and social sustainability. Our approach of focusing on different perspectives and aggregating identified parameters into macro-parameters is a powerful method that allows for a more nuanced and detailed understanding of mental health and its contributing factors. By identifying these factors, this study has the potential to contribute to the development of strategies to reduce exposure to harmful substances and mitigate the negative impacts of social, economic, and environmental factors on mental health. Therefore, the findings of this study have significant implications for the improvement of public health and social sustainability.The findings have the potential to open new avenues for identifying drug use and abuse for mental health, as well as other micro and macro factors related to mental health through social media. The methodology can also be applied to other diseases and may have the potential for forensic toxicology research. However, more research is needed to fully explore the potential of social media for forensic purposes. Moreover, our approach can serve as an autonomous real-time surveillance system that captures crucial system parameters related to mental health, socio-economic factors, and the environment. By detecting opportunities, challenges, and risks, we can take proactive steps toward optimizing society for better, sustainable health outcomes. Moreover, our system\u2019s ability to monitor and analyze a variety of factors in real-time allows for swift and effective action to be taken in response to potential threats to mental health. By continually tracking and assessing these parameters, we can proactively identify potential risks and take steps to mitigate them. This not only improves individual well-being but also helps to create a healthier, more resilient society.The work presented in this paper is the beginning, many more works are needed to investigate the potential of social media for forensic and other purposes. This research is part of our broader work on data-driven parameter discovery from Twitter and other data sources applied previously to different research areas including the education sector in KSA during COVID-19 , the disThis work is scientifically valid as it uses a systematic approach to gather data from Twitter and applies big data and machine learning techniques to analyze the data. The study collected a large sample of over one million tweets in Arabic about psychological health in Saudi Arabia. The use of a large sample increases the statistical power of the study, making it more representative of the population of interest. The study used machine learning algorithms to discover parameters related to mental health from the tweets, which ensures a consistent and replicable approach to the data analysis. The methodology used in the study is comprehensive and transparent. The paper provides a detailed account of how the study was conducted, including the data collection process, machine learning algorithms, and the parameters discovered. This allows other researchers to replicate the study and verify the results. Furthermore, this study identifies the potential for extending the methodology to other diseases and forensic toxicology, further demonstrating the robustness of the methodology. Our methodology and results are applicable to other research domains beyond mental health; therefore, our findings have a level of generality and transferability. This implies that results are not limited to the specific sample, population, or context used in this paper but can be extended to other contexts or populations. This study\u2019s results provide a comprehensive account of mental health from different perspectives, including drugs and treatments, causes and effects, and drug abuse. This study identified 52 parameters from different perspectives related to mental health, which were further aggregated into six macro-parameters. This study\u2019s findings were based on social media discussions by both the public and health professionals, which provides insight into the social and environmental factors that impact mental health. Furthermore, this study identified the associations between different drugs and mental health, which has implications for the effectiveness and risks of medication for treating mental health issues. In conclusion, this study\u2019s comprehensive methodology, large sample size, and use of machine learning algorithms make it scientifically valid. This study\u2019s results provide a valuable contribution to understanding mental health issues from a social and environmental perspective, and the potential for extending the methodology to other diseases and forensic toxicology provides a promising avenue for future research.Mental health issues can have significant impacts on individuals and communities, and addressing root causes can help prevent mental health problems. The big data and machine learning approach proposed in this paper can be used to automatically discover parameters related to mental health from Twitter data, including information on drugs and treatments, causes and effects, and drug abuse. This can provide a comprehensive understanding of mental health as seen on social media, discussed by the public and health professionals, and can also identify associations with different drugs. The methodology can be extended to other diseases and has the potential for discovering evidence for forensic toxicology from social and digital media. Additional research is necessary to fully explore the potential of social media for forensic purposes; this paper is just the beginning and it will form our future work.The conclusions drawn in this work are confirmed by scientific data and objectivity in several ways. First, the paper identifies mental health as a significant issue with impacts on individuals and communities and highlights the need for a holistic approach to understand its root causes. This understanding is supported by scientific research on mental health and the impacts of social and environmental factors on mental health outcomes. Second, we propose a data-driven approach for discovering parameters related to mental health from Twitter data. The use of big data and machine learning tools is a well-established methodology for data analysis and can provide insights into complex problems, including mental health. Third, we report the results of this study that collected over one million Arabic tweets about psychological health in Saudi Arabia. The use of Twitter data provides an objective and real-time view of mental health issues, as discussed by the public and health professionals. The analysis of the Twitter data provides a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse.Although our work on using big data and machine learning to automatically discover parameters related to mental health from Twitter data is innovative and insightful, there are limitations to the study that must be considered. Firstly, the study solely relies on Twitter data, which may not represent the entire population and may suffer from selection bias. Additionally, the study only focuses on Arabic tweets related to mental health in Saudi Arabia during a specific period, which may limit the generalizability of the findings. To address this limitation, more data should be collected and analyzed in Saudi Arabia and internationally. Secondly, the study collected a substantial number of tweets, but further research is needed to capture relevant tweets comprehensively, such as through additional keywords and hashtags. Thirdly, the research focused on three perspectives, and more research is needed to ensure that all perspectives are captured to provide more comprehensive information. Fourthly, there is a need to incorporate other sources of digital media and scientific data to enhance the diversity and richness of the discovered information. Finally, while machine learning algorithms are powerful tools for data analysis, they are not infallible and may produce inaccurate or biased results. We are confident that all the limitations we have identified can be overcome in our future work. As we move forward, we invite the community to join us in improving the proposed approach and enhancing its robustness and impact. Working together, we can achieve our goals and realize the full potential of our efforts."} +{"text": "The last five decades have witnessed an inordinate number of advances in the diagnosis and management of congenital heart defects (CHDs), as reviewed elsewhere . These aIn the first paper, Vecchiato and associates from Padova and Naples, Italy, discuss the overshoot of the respiratory exchange ratio during recovery from maximal exercise testing in young patients with congenital heart disease (CHD) . The autIn the second paper, Sganga and her colleagues from Harvard Medical School, Boston, MA, and Stanford University School of Medicine, Palo Alto, CA, USA review quality improvements in a pediatric echocardiography laboratory . The autIn the third paper, Dr. Pop from the University of Medicine Pharmacy Sciences and Technology of Tirgu Mures and the Tirgu Mures Emergency Institute for Cardiovascular Diseases and Heart Transplant, Tirgu Mures, Romania, compares different contrast agents used for computed tomographic angiography (CTA) studies in infants referred for aortic arch evaluation . Dr. PopIn the paper to follow, I review clinical aspects of mitral atresia with normal aortic root . Mitral In the next paper, Dr. Singh from the Baylor College of Medicine/The Children\u2019s Hospital of San Antonio, San Antonio, TX, USA, reviews \u201cas low as reasonably achievable\u201d (ALARA) in pediatric electrophysiology laboratory . Dr. SinIn the sixth paper, Dr. Divekar and associates from the University of Texas Southwestern Medical Center/Children\u2019s Medical Center, Dallas, TX, USA, and the Cleveland Clinic Children\u2019s Hospital, Cleveland, OH, USA, review transcatheter device therapy and how to integrate advanced imaging with invasive procedures in the management of CHD . These aIn the subsequent paper, Dr. Arar and his colleagues at the University of Texas Southwestern Medical Center/Children\u2019s Medical Center, Dallas, TX, USA, review the role of cross-sectional imaging in pediatric interventional cardiac catheterization . This paIn the next paper, Dr. Betancourt and her associates from The Children\u2019s Hospital of San Antonio/Baylor College of Medicine, San Antonio, TX, USA, review the utility of a three-dimensional printed model in the biventricular repair of complex CHDs . They rep = 0.27). In addition, no difference in time to first oral feed (2.0 days (1.1\u20134.5) vs. 3.1 days (1.8\u20134.4), p = 0.34) and time to goal feed (6.0 days (3.2\u20138.3) vs. 6.9 days (5.0\u20139.0), p = 0.15) was detected. Furthermore, no variance in establishing all oral feeds in one year: 88% vs. 98%, p = 0.16 was identified. However, the delayed group performed substantially worse on all the above parameters. The authors conclude that immediate and early groups demonstrated no variations in feeding outcomes or length of stay in their investigation, while the delayed group performed worse on all measures. Consequently, they recommend that caregivers focus on extubating the babies within 3 days following surgery to enhance feeding outcomes while reducing hospitalization duration.In a subsequent paper, Kepple and his associates from Creighton University School of Medicine and University of Nebraska Medical Center, Omaha, NE, USA, review the impact of extubation time on feeding outcomes after neonatal cardiac surgery . The autIn the final paper of this series, Dr. Sharma and associates from The Children\u2019s Hospital of San Antonio/Baylor College of Medicine, San Antonio, TX, USA, and the Cohen Children\u2019s Medical Center, New York, NY, USA, discuss advances in the prenatal management of fetal cardiac disease . They stThe papers included in this Special Issue, while not addressing all the advances that occurred in the last 50 years , have in"} +{"text": "Incorrect AffiliationIn the published article, there was an error in affiliation 7. Instead of \u201cDepartment of Chemistry, College of Science, Princess Noura bint Abdulrahman University, Riyadh, Saudi Arabia\u201d, it should be \u201cDepartment of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Correction: Liu et al. BMC Medical Imaging (2023) 23:14710.1186/s12880-023-01077-4Following the publication of the original article [1], it was brought to our attention that an error had been introduced during typesetting. In the article [1], it was stated that the Corresponding Author, Zhentao Li, was affiliated with United Imaging Intelligence (Beijing) Co., Ltd, located at Yongteng North Road, Haidian District, Beijing 100,094, People\u2019s Republic of China.The correct affiliation for Zhentao Li should have been the Department of Radiology, Peking University People\u2019s Hospital, located at 11 Xizhimen Nandajie, Xicheng District, Beijing, 100,044, People\u2019s Republic of China.The author group information has been updated accordingly, and the original article has been"} +{"text": "Patient blood management (PBM) is a multidisciplinary and patient-centered treatment approach, comprising the detection and treatment of anemia, the minimization of blood loss, and the rational use of allogeneic transfusions. Pregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia, which correlates with worse maternal and fetal outcomes and places pregnant women at increased risk of obstetric hemorrhage.off-label use of human recombinant erythropoietin in selected patients. This regimen should be tailored to the needs of each individual patient. Postpartum hemorrhage (PPH) accounts for up to one-third of maternal deaths in both developing and developed countries. Bleeding complications should be anticipated and blood loss reduced by interdisciplinary preventive measures and individually tailored care. It is recommended that facilities have a PPH algorithm, primarily focusing on prevention through use of uterotonics, but also incorporating early diagnosis of the cause of bleeding, optimization of hemostatic conditions, timely administration of tranexamic acid, and integration of point-of-care tests to support the guided substitution of coagulation factors, alongside standard laboratory tests. Additionally, cell salvage has proven beneficial and should be considered for various indications in obstetrics including hematologic disturbances, as well as various forms of placental disorders.Early screening for iron deficiency before the onset of anemia, as well as the use of oral and intravenous iron to treat iron deficiency anemia, has been shown to be beneficial. Anemia in pregnancy and the puerperium should be treated according to a staged regimen, administering either iron alone or in combination with an This article reviews PBM in pregnancy, delivery, and the puerperium. The concept comprises early screening and treatment of anemia and iron deficiency, a transfusion and coagulation algorithm during delivery, as well as cell salvage. Patient blood management (PBM) is a multidisciplinary and patient-centered treatment approach, comprising the detection and treatment of anemia, the minimization of blood loss, and the rational use of allogeneic transfusions. So far, the focus of PBM has been on major elective surgeries. Given the success of PBM initiatives , it seemPregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia , 3, 4, wAnemia in pregnancy is defined by the WHO as a hemoglobin level <110 g/L. Worldwide, up to 40% of pregnant women receive a diagnosis of anemia . In EuroThe leading cause of anemia in pregnancy as well as postpartum is iron deficiency , 14. TheIron deficiency has detrimental effects on physical and mental performance, thermoregulation, immune function, neurologic function, and enzymatic function , with the consequence that maternal mortality rises with increasing severity of iron deficiency anemia . In geneThe administration of iron without actual knowledge of iron status is considered controversial , 27. AccBy contrast, diagnosed iron deficiency should be treated, as even mild anemia can be unpredictable, suddenly worsening over the course of a pregnancy with attendant risks to the mother and fetus. The mode of therapy should take into account various factors, including time remaining until delivery, the severity of anemia, the likelihood of additional complications , maternal comorbidities, and the patient's wishes Fig. 2)2).Oral iron is the gold standard for the treatment of mild to moderate iron deficiency anemia . Higher Gastrointestinal side effects such as constipation, heartburn, and nausea, which occur in up to 30% of patients and limit the dose which can be administered, are a major disadvantage of oral iron preparations , 38, 39.Intravenous iron preparations are an important adjunct or alternative to oral iron therapy and allogenic blood transfusion. Indications for intravenous iron therapy include inadequate therapeutic response to oral iron therapy, anemia requiring rapid normalization, or simultaneous use of erythropoiesis stimulating proteins .Intravenous iron administration bypasses the intestinal mechanism of iron absorption and therefore often results in an increase in free iron in serum after intravenous iron administration . DespiteA first, hemoglobin and ferritin measurement is normally performed in the first trimester and an oral iron therapy is usually prescribed in case of hemoglobin <100 g/L and/or ferritin <30 g/L. In the case of a lack of response to oral iron (Hb levels rising by less than 10 g/L within 14 days), severe iron-deficiency anemia, intolerance of oral iron, or clinical need for rapid and efficient treatment of anemia , intravenous iron therapy should be administered in the absence of contraindications but not before 16 weeks of gestation .The intravenous iron preparations used today differ in terms of pharmacokinetics, molecular mass, toxicity, and side effects . Meta-anSeveral studies have confirmed the efficacy and safety of parenteral iron as ferrous saccharate in iron deficiency and anemia in pregnancy , 47, 48.Study data are available for other intravenous iron preparations too, for example, iron polymaltose, iron gluconate, and low molecular weight iron dextrans . In geneThe growth factor rhEPO, a glycoprotein , is identical to endogenous erythropoietin and serves as a selective growth and survival factor for erythroid cells . Of releMeanwhile, there is also increasing experience using rhEPO in obstetrics , 64, 65.According to present results, the combination of rhEPO and parenteral iron is superior to iron therapy alone in terms of raising hemoglobin concentration and may be considered as an alternative in severe anemia or rejection of allogenic blood transfusion . The effThe coagulation cascade as classically taught, with extrinsic and intrinsic pathways converging on a final common pathway of thrombin formation, does not fully capture the true nature of in vivo clot formation . A more In this model, the exposure of TF-bearing cells to factor VII activates the extrinsic pathway leading to the formation of a small amount of thrombin. This small amount of thrombin then amplifies the pro-coagulant response by activating cofactors, factor XI, and platelets. Following that, a large burst of thrombin is formed on the platelet surface via the intrinsic pathway. Thus, the extrinsic and intrinsic pathways are not redundant but rather work in concert to bring about adequate secondary hemostasis ending in conversion of fibrinogen in fibrin monomers .3, due to a combination of hemodilution, and rapid turnover in the uteroplacental unit [Pregnancy is characterized by multiple changes to this system Fig. 3)3). Firsttal unit , 76.Third, and perhaps most importantly, there is an altered baseline coagulation status in pregnancy. The most notable change with respect to the nonpregnant state is a progressive rise in fibrinogen (factor I) concentration, peaking at 24 h postpartum , 79, 80.Standard laboratory tests of coagulation do not reliably reflect the hypercoagulable state of pregnancy , 89, 90.Coagulation disorders in the setting of preeclampsia, HELLP syndrome, or disseminated intravascular coagulation often result in high blood loss. Other, more common, situations with a risk for massive hemorrhage arise from the placenta accreta spectrum, or placental abruption. 90% of patients with placenta accreta spectrum have blood loss >2,000 mL, which is associated with an increased risk of allogeneic blood transfusion. PPH is defined as blood loss in excess of 500 mL independent of delivery mode .The four leading causes of PPH are uterine atony, accounting for up to 80% of cases, as well as trauma, placental disorders, and coagulation defects, although PPH can also occur in women without any of these risk factors. These are also known as the \u201cfour Ts\u201d: tone, trauma, tissue, and thrombin , 105. AsMeasures for the prevention of PPH suggested by the World Health Organization (WHO) include the administration of uterotonics, primarily oxytocin, late cord clamping , controlled cord traction for placental removal, and assessment of uterine tone in all women . The treConsidering the importance of rapid correction of hemostasis during PPH, viscoelastic point-of-care tests, such as ROTEM and TEG, have been proven to be of great value in the assessment of bleeding, by allowing for individualized coagulation management according to each patient's needs . PPH algFocusing on the second pillar of PBM, the reduction of perioperative red blood cell loss, the use of a cell salvage can also be applied in a peripartum setting. Historically, the idea of collecting a patient's own blood was born in obstetrics when the case of a woman who died of PPH provoked William Highmore to write a letter to The Lancet in 1874, stating that re-transfusing the lost blood could have saved the patient's life. In the past few decades, cell salvage has been implemented in various surgical settings. Despite this auspicious start, clinicians were initially cautious in obstetrics, due to concerns regarding amniotic fluid embolism and the re-transfusion of fetal debris potentially causing maternal alloimmunization. However, a focused review by Goucher et al. of over Within obstetrics, cell salvage should be considered for various indications, especially various forms of placental disorders . FurtherPregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia, which correlates with worse maternal and fetal outcomes and places pregnant women at increased risk of obstetric hemorrhage. Iron deficiency and anemia in pregnancy and the puerperium should be treated according to a staged regimen, administering either iron alone or in combination with human recombinant erythropoietin in selected patients. This regimen should be tailored to of the needs of each individual woman. It is recommended that obstetric facilities have a PPH algorithm, which incorporates early diagnosis of the cause of bleeding, optimization of hemostatic conditions, timely administration of TXA as well as oxytocin, and integration of point-of-care tests to support the guided substitution of coagulation factors, alongside standard laboratory tests. Cell salvage has been shown to be safe and beneficial and should be considered for various indications in obstetrics.David Hencker and Clara Castellucci have no conflicts of interest to declare. Alexander Kaserer received honoraria for lecturing from Bayer AG, Z\u00fcrich, Switzerland. Christian Breymann is medical advisor in the field of iron therapy in OBGYN and received honoraria for lecturing from Vifor International and Pierre Fabre Switzerland. Donat R. Spahn's academic department is receiving grant support from the Swiss National Science Foundation, Berne, Switzerland, the Swiss Society of Anesthesiology and Perioperative Medicine (SSAPM), Berne, Switzerland, the Swiss Foundation for Anesthesia Research, Zurich, Switzerland, Vifor SA, Villars-sur-Gl\u00e2ne, Switzerland, and Vifor AG, St. Gallen, Switzerland. Dr. Spahn is co-chair of the ABC-Trauma Faculty, sponsored by unrestricted educational grants from Novo Nordisk Health Care AG, Zurich, Switzerland, CSL Behring GmbH, Marburg, Germany, LFB Biom\u00e9dicaments, Courtaboeuf Cedex, France, and Octapharma AG, Lachen, Switzerland. Dr. Spahn received honoraria/travel support for consulting or lecturing from Danube University of Krems, Austria, European Society of Anesthesiology and Intensive Care, Brussels, BE, Korean Society for Patient Blood Management, Seoul, Korea, Korean Society of Anesthesiologists, Seoul, Korea, Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis, Paris, France, Alexion Pharmaceuticals Inc., Boston, MA, AstraZeneca AG, Baar, Switzerland, Bayer AG, Z\u00fcrich, Switzerland, B. Braun Melsungen AG, Melsungen, Germany, CSL Behring GmbH, Hattersheim am Main, Germany and Berne, Switzerland, Celgene International II S\u00e0rl, Couvet, Switzerland, Daiichi Sankyo AG, Thalwil, Switzerland, Haemonetics, Braintree, MA, USA, Instrumentation Laboratory (Werfen), Bedford, MA, USA, LFB Biom\u00e9dicaments, Courtaboeuf Cedex, France, Merck Sharp & Dohme, Kenilworth, NJ, USA, Novo Nordisk Health Care AG, Zurich, Switzerland, PAION Deutschland GmbH, Aachen, Germany, Pharmacosmos A/S, Holbaek, Denmark, Pfizer AG, Z\u00fcrich, Switzerland, Pierre Fabre Pharma, Alschwil, Switzerland, Portola Schweiz GmbH, Aarau, Switzerland, Roche Diagnostics International Ltd, Reinach, Switzerland, Sarstedt AG & Co., Sevelen, Switzerland and N\u00fcmbrecht, Germany, Shire Switzerland GmbH, Zug, Switzerland, Takeda, Glattpark, Switzerland, Tem International GmbH, Munich, Germany, Vifor Pharma, Munich, Germany, Neuilly sur Seine, France and Villars-sur-Gl\u00e2ne, Switzerland, Vifor AG, St. Gallen, Switzerland, and Zuellig Pharma Holdings, Singapore, Singapore.Concept and design: Donat R. Spahn and Alexander Kaserer. Drafting of the manuscript: Alexander Kaserer, Clara Castellucci, David Henckert, and Christian Breymann. Figures: Alexander Kaserer and David Henckert. All authors critically edited the manuscript, approved the final version to be submitted, and agree to be accountable for the accuracy and integrity of the work."} +{"text": "Dear Editor, Leishmaniasis is a neglected tropical disease caused by a parasite transmitted by infected female sandflies. There are 3 main forms of the disease :Cutaneous leishmaniasis (Cl) is the most common form and causes skin lesions, mainly ulcers, on exposed parts of the body (see examples in Figure 1 Mucocutaneous leishmaniasis leads to partial or total destruction of mucous membranes of the nose, mouth and throat. Over 90% of mucocutaneous leishmaniasis cases occur in Bolivia, Brazil, Ethiopia and Peru.Visceral leishmaniasis, also known as kala-azar, is fatal if left untreated in over 95% of cases. Most cases occur in Brazil, east Africa and India. An estimated 50,000 to 90,000 new cases occur worldwide annually. Visceral leishmaniasis is highly endemic in Iraq, Somalia, Sudan and Yemen.Several Leishmania spp. can cause Cl, but most infections probably remain symptomless. The first sign of an infection is typically a small erythema, which develops into a papule, then a nodule that progressively ulcerates over a period of 2 weeks to 6 months. Lymphatic spread and lymph-gland involvement, which may precede lesion development, are common and there is a variable tendency for lesions to self-heal . In addiHealthy skin is essential for physical well-being and can have a significant impact on an individual's self-reliance and sexual attractiveness. Cl can make life very difficult for affected individuals, as the visible skin lesions can create emotional distress and make routine relationships with close relatives and friends difficult, particularly when the lesions are visible in exposed parts of the body.In addition to the psycho-social effects of visible lesions, the permanent scars left by the disease can negatively impact an individual's quality of life, creating social issues and psychological symptoms. As such, it is important for healthcare providers to take a holistic approach to managing and treating leishmaniasis, addressing both the physical and psycho-social aspects of the disease to improve outcomes for affected individuals .Quality of life is a subjective perception that is influenced by an individual's values, culture, goals, standards, expectations, and concerns. This concept is particularly relevant in chronic diseases like leishmaniasis, as it can help capture the disease's social and psychosomatic impact and the effectiveness of therapeutic interventions. By taking a comprehensive approach to the management and treatment of leishmaniasis, healthcare providers can improve the quality of life for affected individuals . Assessing patients\u2019 quality of life with Cl can improve our understanding of their needs and the psycho-social consequences of the disease. This can help develop effective therapeutic solutions, improving outcomes for affected individuals. By taking a patient-centred approach, healthcare providers can optimize outcomes and improve the overall quality of life for those with leishmaniasis. This may involve tailored treatment plans and ongoing support and education for patients to manage the disease and its effects on their daily lives . Cl can have significant physical and psychological impacts on patients\u2019 quality of life. To create a better quality of life for affected individuals, healthcare professionals should consider all aspects of the disease in conjunction with therapeutic interventions. In addition, evaluating the extent of disease involvement and characteristics such as the number, size, and duration of scars, along with potential side effects of treatment and residual lesions, is crucial for planning a successful patient care management program. By taking a comprehensive approach that addresses the disease\u2019s physical and psycho-social aspects, healthcare providers can improve outcomes and quality of life for those with Cl.For countries where Cl is not endemic, it is important to know where leishmaniasis is endemic in order to be aware of the disease in travellers returning with symptoms. About 95% of Cl cases occur in the Americas, the Mediterranean basin, the Middle East and central Asia. Cl is highly endemic in Algeria, whereas for West Africa, the epidemiological information is scarce. In East Africa, all forms are endemic. In the following countries leishmaniasis is endemic :Afghanistan, Albania, Algeria, Argentinia, Azerbajan, Belize, Bhutan, Bolivia, Bosnia and Herzegovina, Brazil, Bulgaria, Burkina Faso, Cameroon, Central African Republic, Chad, China, Colombia, Costa Rica, Croatia, Cyprus, C\u00f4te d\u2019Ivoir, Democratic Republic Congo, Djbouti, Dominican Republic, Ecuador, Egypt, El Salvador, Eritrea, Ethiopia, France, French Guiana, Gambia, Georgia, Ghana, Greece,Guatemala, Guinea, Guinea-Bissau, Guyana, Honduras, India, Iran, Iraq, Israel, Italy, Jordan, Kazakhstan, Kenya, Kuwait, Kyrgyzstan, Lebanon, Libya, Malawi, Mali, Malta, Mauritania, Mexico, Monaco, Montenegro, Morocco, Namibia, Nepal, Nicaragua, Niger, Nigeria, Oman, Pakistan, Panama, Paraguay, Peru, Portugal, Republic of North Macedonia, Saudi Arabia, Senegal, Slovenia, Spain, Sri Lanka, Siudan, Suriname, Syrian Arab Republic, Taiwan, Tajikistan, Thailand,Tunisia, Turkmenistan, Turkey, Ukraine, USA, Uzbekistan, Venezuela, Palestine, and Yemen. In northern and central Europe, no authochthonus cases have been reported. That is, in Germany, leishmaniasis occurs almost as an imported disease. In 2000, a reference centre for the diagnosis and therapy of leishmaniasis was opened at the Institute for Tropical Medicine, Berlin, Germany. During the first two years, 58 cases of leishmaniasis were imported . Up to 2The authors declare that they have no competing interests.Not applicable0000-0003-2794-1508The ORCID ID of Azami M is:"} +{"text": "Due to the increase in life expectancy and the aging of the global population, the \u201cBelt and Road\u201d (\u201cB&R\u201d) countries are faced with varying degrees of lung cancer threat. The purpose of this study is to analyze the differences in the burden and trend of lung cancer disability in the \u201cB&R\u201d countries from 1990 to 2019 so as to provide an analytical strategic basis to build a healthy \u201cB&R\u201d.Data were derived from the Global Burden of Disease 2019 (GBD 2019). Incidence, mortality, prevalence, the years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lung cancer and those attributable to different risk factors were measured from 1990 to 2019. Trends of disease burden were estimated by using the average annual percent change (AAPC), and the 95% uncertainty interval (UI) was reported.China, India, and the Russian Federation were the three countries with the highest burden of lung cancer in 2019. From 1990 to 2019, the AAPC of incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), most countries in North Africa, and the Middle East, the trend was mainly upward. The AAPC of age-standardized incidence was 1.33% (1.15%\u20131.50%); the AAPC of prevalence, mortality, and DALYs from lung cancer in China increased by 24% (2.10%\u20132.38%), 0.94% (0.74%\u20131.14%), and 0.42% (0.25%\u20130.59%), respectively. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the vast majority of \u201cB&R\u201d countries, but for women, most countries had an upward trend. For adults aged 75 years or older, the age-standardized YLD rate showed an increasing trend in most of the \u201cB&R\u201d countries. Except for the DALY rate of lung cancer attributable to metabolic risks, a downward trend of the DALY rate attributable to all risk factors, behavioral risks, and environmental/occupational risks was shown in the vast majority of \u201cB&R\u201d countries.The burden of lung cancer in \u201cB&R\u201d countries varied significantly between regions, genders, and risk factors. Strengthening health cooperation among the \u201cB&R\u201d countries will help to jointly build a community with a shared future for mankind. The \u201cBelt and Road\u201d (\u201cB&R\u201d) Initiative refers to the \u201cSilk Road Economic Belt\u201d and the \u201c21st Century Maritime Silk Road\u201d, which was first proposed by China in 2013. \u201cB&R\u201d countries run through Eurasia, connecting the Asia Pacific Economic Circle in the east and the European Economic Circle in the west . Detailed methodology has been published elsewhere study obtained from the Institute for Health Metrics and Evaluation (IHME) website. All data for this study were obtained from the Institute for Health Metrics and Evaluation (IHME) website . YLLs are calculated as the product of counts of deaths caused by lung cancer and a standard remaining life expectancy at the age of death. The age-standardized rates were corrected by the direct method and the world standard population to account for differences in the population age structure. Our study follows the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) to ensure transparency and replicability Table\u00a01 The 66 members of \u201cB&R\u201d countries are as follows: 1) East Asia: China; 2) Central Asia: Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Mongolia, Tajikistan, Turkmenistan, and Uzbekistan; 3) South Asia: Bangladesh, Bhutan, India, Nepal, and Pakistan; 4) Southeast Asia: Cambodia, Indonesia, Laos, Malaysia, Maldives, Burma, the Philippines, Sri Lanka, Thailand, and Vietnam; 5) high-income Asia Pacific: Brunei and Singapore; 6) North Africa and the Middle East: Afghanistan, Bahrain, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Saudi Arabia, Syria, Turkey, the United Arab Emirates, and Yemen; 7) Central Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Hungary, Montenegro, North Macedonia, Poland, Romania, Serbia, Slovakia, and Slovenia; 8) Eastern Europe: Belarus, Estonia, Latvia, Lithuania, Republic of Moldova, Russia, and Ukraine; 9) Western Europe: Cyprus, Greece, and Israel. See p < 0.05 was considered statistically significant.We calculated absolute numbers and age-standardized rates of incidence, mortality, YLDs, and DALYs to quantify the burden of lung cancer, grouped by gender and age in the \u201cB&R\u201d countries. Age-standardized estimates allow comparisons across time, countries, and subregions and are adjusted for differences in the age distribution of the population. Age was divided into three groups: 20\u201354 years, 55\u201374 years, and \u226575 years. The three risk factors were included in the present study. Data were stratified by region . SDI is a composite indicator of a country\u2019s lag-distributed income per capita, educational attainment, and the total fertility rate in women younger than 25 years. Methods of SDI development and computation are detailed elsewhere . Trends Being involved in the Global Burden of Disease 2019 and other open databases rather than directly speaking to patients inspired this research. Although no patient was directly involved in this study, members of the public read our manuscript, and all agreed on the specific findings of this study.The absolute number of incidence, mortality, YLDs, and DALYs in 2019 caused by lung cancer in each member country of the \u201cB&R\u201d are shown in p < 0.001), 2.24% , 0.94% , and 0.42% , respectively. See From 1990 to 2019, the AAPC of age-standardized incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), and most countries in North Africa and the Middle East, the trend was mainly upward Figure\u00a03p < 0.05) (p < 0.05). For adults aged 75 years or older, the age-standardized YLD rate from 1990 to 2019 showed an increasing trend in the \u201cB&R\u201d countries, except Kazakhstan, Kyrgyzstan, Turkmenistan, Mongolia, Bangladesh, Maldives, Afghanistan, Bahrain, the United Arab Emirates, Belarus, Moldova, Ukraine, Greece, and the Philippines. In China, age-standardized YLDs showed an increasing trend with the increase of age, and the highest AAPC value of age-standardized YLD rate from 1990 to 2019 was in adults aged 75 years or older: 2.87% . See p < 0.05).p < 0.05).For DALYs of lung cancer attributable to behavioral risks, the age-standardized DALY rate of middle SDI regions, China, Georgia, Bhutan, Bhutan, Indonesia, Sri Lanka, Vietnam, Afghanistan, Egypt, Jordan, Lebanon, Palestine, Bulgaria, Montenegro, Macedonia, Serbia, and Cyprus showed an increasing trend in the \u201cB&R\u201d countries from 1990 to 2019 .For DALYs of lung cancer due to environmental/occupational risks, the age-standardized DALY rate of Georgia, Bhutan, Pakistan, Sri Lanka, Egypt, Iran, Iraq, Jordan, Lebanon, and Bulgaria showed an increasing trend in the \u201cB&R\u201d countries from 1990 to 2019 . See For DALYs of lung cancer attributable to metabolic risks, the age-standardized DALY rate of Kazakhstan, Kyrgyzstan, Turkmenistan, Maldives, the Philippines, Thailand, Singapore, Bahrain, Slovakia, Belarus, and Ukraine showed a decreasing trend in the \u201cB&R\u201d countries from 1990 to 2019 (all With an estimated 1.79 million deaths per year, lung cancer is one of the leading causes of cancer-related deaths . SmokingOur study found significant differences in the trend of age-standardized YLDs between genders. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the \u201cB&R\u201d countries. For women, the upward change trend of YLDs was observed in most countries. The global incidence of lung cancer in men is declining twice as fast as in women . The ageThe increase in life expectancy has led to a greater global burden of diseases. Global population aging is the principal medical and social demographic problem worldwide. In the Non-Organisation for Economic Co-operation and Development countries, the fastest-aging countries are Saudi Arabia, Brazil, and China . Since 2In recent decades, countries within the Middle East have faced social, political, and financial instability brought about by war. These conflicts have directly led to a significant decline in the overall level of local medical services and a shortage of professional experts, seriously affecting the provision of cancer diagnosis services. The cancer patients in these areas cannot be diagnosed early and cannot receive effective healthcare , 23. In With a deeper understanding of the biology of lung cancer, many advances have been made in the treatment of lung cancer, such as minimally invasive techniques, stereotactic ablative radiotherapy, targeted therapies, and ICIs . New theYLDs can reflect the amount of time lived in states of less than good health due to a specific disease or injury and are calculated as the prevalence of a sequela of any given cause multiplied by the average duration until death or remission and by the disability weight for that sequela. The YLDs are the sum of each of the sequelae associated with the disease or injury , 27. YLLGlobally, from 2010 to 2019, the number of lung cancer increased by 23.3%, and the age-standardized incidence rates decreased by 7.4% in men and increased by 0.9% in women . All theUnlike previous lung cancer burden studies based on GBD data, this study focuses on the \u201cB&R\u201d countries proposed by China, the world\u2019s second-largest economy, under the global community of shared future strategy. It not only describes the changes in disease burden in a specific region or globally but also provides targeted data support for how countries with significant differences in social demographic indices but strong political and economic connections can formulate policies to reduce the burden of lung cancer. Preventive measures such as smoking control interventions and air quality management should be prioritized in low and middle SDI regions. Our research also suggested that we should pay more attention to female lung cancer patients. For women, the upward trend of YLDs was observed in the \u201cB&R\u201d countries, and it may continue to rise in the future . By studThis study also has several limitations. First, GBD 2019 has inherent limitations that are applicable to this study. Second, the GBD database lacks lung cancer\u2019s pathological staging and classification. In the future, the \u201cB&R\u201d countries can use economic development as a link to drive the construction of information-based disease monitoring systems, providing sufficient support for the estimation of disease burden and policy adjustments.In summary, the overall burden of lung cancer in the \u201cB&R\u201d countries is still huge, especially in China, South Asia, North Africa, and the Middle East. There are significant differences between genders and ages. The lung cancer prevention and treatment policies in women and adults aged 75 years or older need to be improved. With the background of the health \u201cB&R\u201d Initiative, multi-country cooperation and experience sharing will play an important role in jointly facing the challenges caused by lung cancer and promoting the positive development of healthcare in all member countries.The original contributions presented in the study are included in the article/XL conceived and designed the study. ZZhu, WY, LZ, WJ, BC,QW, XC, SY, and ZZhang analyzed the data. ZZhu, XL, and YD provided significant advice and consultation. WY and XL wrote the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "In \u201cPerformance of a Web-Based Reference Database With Natural Language Searching Capabilities: Usability Evaluation of DynaMed and Micromedex With Watson\u201d the authors noted two errors.1. The Authors Contributions section currently reads as:All authors contributed to the study conception; design; and acquisition, analysis, or interpretation of the data. AR, PMG, AS, LAV, DLS, GPJ, and DWB were responsible for study conception or design. PMG, HHE, DLS, and MGA developed the interview guides. MM, AS, SD, and LPN conducted participant recruitment. PMG acted as the interview moderator and had either AR or MM assisting with data collection during testing. PMG, MM, JC, and SD abstracted the data from interview recordings. Data analysis was performed by PMG, MM, and AR. The first draft of the manuscript was written by AR and PMG, with all authors reviewing the draft and providing critical feedback. All authors contributed to and approved the final manuscript.And will be changed to:RR and DWB are co-senior authors and contributed equally.All authors contributed to the study conception; design; and acquisition, analysis, or interpretation of the data. AR, PMG, AS, LAV, DLS, GPJ, and DWB were responsible for study conception or design. PMG, HHE, DLS, and MGA developed the interview guides. MM, AS, SD, and LPN conducted participant recruitment. PMG acted as the interview moderator and had either AR or MM assisting with data collection during testing. PMG, MM, JC, and SD abstracted the data from interview recordings. Data analysis was performed by PMG, MM, and AR. The first draft of the manuscript was written by AR and PMG, with all authors reviewing the draft and providing critical feedback. All authors contributed to and approved the final manuscript.2. In the original article, the ORCID number for Petra Schultz was reported as follows:0000-0001-7337-1046And has been updated to:0000-0001-7949-9243The correction will appear in the online version of the paper on the JMIR Publications website on May 18, 2023, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Anisakis are still common. The Y-shaped lateral cord\u00a0is not unique to Anisakis spp. Acquiring a history of ingesting raw/undercooked fish/seafood can be a clue to the diagnosis of the condition. This review emphasizes the following key points: insufficient awareness of fish parasites among medical professionals, seafood handlers, and policy makers; limited availability of effective\u00a0diagnostic methodologies; and inadequate clinical information for optimizing the\u00a0management of anisakidosis\u00a0in numerous regions worldwide.A review was conducted to identify the most common causative agents of anisakidosis, the methods used for identification of the causative agents, and to summarize the sources of infection, and patients\u2019 demographics. A total of 762 cases were found between 1965 and 2022. The age range was 7 months to 85 years old. Out of the\u00a034 countries, Japan, Spain, and South Korea stood out with the highest number of published human cases\u00a0of anisakidosis, respectively. This raises the question: Why\u00a0are there few to no\u00a0reports of anisakidosis cases in other countries, such as Indonesia and Vietnam, where seafood consumption is notably high? Other than the gastrointestinal tract, parasites were frequently found in internal organs such as liver, spleen, pancreas, lung, hiatal and epigastric hernia, and tonsils. There are also reports of the worm being excreted through the nose, rectum, and mouth. Symptoms included sore throat, tumor, bleeding, gastric/epigastric/abdominal/substernal/lower back/testicular pain, nausea, anorexia, vomiting, diarrhea, constipation, intestinal obstruction, intussusception, blood in feces, hematochezia, anemia, and respiratory arrest. These appeared either immediately or up to 2 months after consuming raw/undercooked seafood and lasting up to 10 years. Anisakidosis commonly mimicked symptoms of cancer, pancreatitis, type I/II Kounis syndrome, intussusception, Crohn\u2019s disease, ovarian cysts, intestinal endometriosis, epigastralgia, gastritis, gastroesophageal reflux disease, hernia, intestinal obstruction, peritonitis, and appendicitis. In these cases, it was only after surgery that it was found these symptoms/conditions were caused by anisakids. A range of not only mainly marine but also freshwater fish/shellfish were reported as source of infection. There were several reports of infection with >1 nematode (up to >200), more than one species of anisakids in the same patient, and the presence of L4/adult nematodes. The severity of symptoms did not relate to the number of parasites. The number of anisakidosis cases is grossly underestimated globally. Using erroneous taxonomic terms, assumptions, and identifying the parasite as The online version contains supplementary material available at 10.1007/s00436-023-07881-9. Anisakis, and (3) pseudoterranovosis caused by members of the genus Pseudoterranova anisakidosis caused by any members of the family Anisakidae, (2) anisakiosis caused by members of the genus Anisakis alone comprises of at least 9 species of infected people with anisakid nematodes and to answer these questions: What are the parasite species reported as the causative agent? What was the possible source of infection? What method was used to identify the parasite and/or diagnose the disease? What symptoms were presented? The review was based on the publicly available information. A review of peer-reviewed literature for topics on Anisakiasis, OR Anisakidosis OR Anisakiosis, was conducted through a search of the Google Scholar, Web of Science, PubMed, and Scopus databases. The bibliographies of the articles found through the search were checked for any other articles relevant to the topic. All languages were included. Following this, some gray literature, such as conference abstracts and proceedings, were also included after ensuring there was no associated publication, acknowledging the lack of peer review for this type of literature. The literature was last searched on 1st February 2023. Although Data including authors, year of publication, country, age, and gender of the patient, diagnostic techniques for the disease, method of parasite identification, parasite ID, developmental stage of the parasite, number of parasites found in the patient, infected organs, symptoms, treatment, the time between consuming seafood and emergence of the symptoms, duration of the symptoms, and possible source of infection were recorded in an MS Excel sheet.Hysterothylacium spp. These 409 articles reported 762 cases dated between 1965 and the end of 2022 , it was found that the minimum and maximum age of infected people was 7 months old and 85 years old . In 27 cases in which more than 10 anisakid larvae was reported , acute biliary pancreatitis, autoimmune pancreatitis, type I and II Kounis syndrome, colonic intussusception, Crohn\u2019s disease, enlarged bilateral ovarian cysts, intestinal endometriosis, epigastralgia, gastritis, gastroesophageal reflux disease, hernia, intestinal obstruction, ileum to ileum intussusception caused by Meckel\u2019s diverticulum, peritonitis, acute appendicitis, acute arthritis of knees, elbows and ankles, and non-anisakid parasitic disease.Engraulis encrasicolus) pickled in vinegar, a typical Mediterranean food), croaker fish, fish swimbladder, raw mackerel, abalone, penis fish, assorted sashimi , baked cod, catfish, ceviche, cod liver, conveyor belt sushi , raw sea bream, eel sashimi, empurau fish (Tor tambroides), fish eggs, flatfish, yellowtail, flounder sashimi, fresh cured Alaskan salmon, poke style raw tuna from Alaska, grilled scabbard fish, hake, herring fish, home-cured salmon gravlax, marinade bluefish, marinated mackerel, marinated pilchards, raw Atlantic salmon , raw bonito, raw clams, raw cuttlefish, raw oyster, raw Pacific saury, raw salted fish or squid , shrimp, raw yellowtail, redfish/sushi, rockfish (Sebastes sp.), fresh slices of raw jacopever, shabu-shabu (mackerel fish), trout, sliced raw fish (Sebastes schlegelii), ascidians, and a piece of flatfish gut, prior to the disease occurrence. The source of these fish was not only mainly from marine waters but also occasionally from freshwater and local rivers. Based on the history provided by patients, the onset of the symptoms was highly variable, starting from immediately to 2 months after consumption of the abovementioned seafood. In one case, the duration of symptoms was up to 10 years of intermittent pain.The source of infections, based on the patients\u2019 reports, was a wide range of seafood. These included marinated anchovies , and considerable variations in the pattern of occurrence by year, the number of publications is clearly higher since the beginning of the millennium. Although we included publications since 1965, there are reports of human cases dating back to the nineteenth century. For example, in 1867, a nematode had been vomited by a child from a fishing community on the West Coast of Greenland and identified as Leuckart . Ascarise Martin . In anote Martin . In Japae Martin . In 1960e Martin . The tote Martin ; howevere Martin , in addiOur review suggests that, globally, the parasite is more common among people aged 31-60 years, similar to the age groups reported in country-focused studies. Cha and Mee Sun , based oAs previously shown by other authors were reported in humans Gibson , suggestm Oshima . The absHysterothylacium larva is also important , Hysterothylacium larvae penetrated the stomach wall, causing hemorrhage and attracted eosinophils"} +{"text": "In the published article, there was an error regarding the affiliations for authors Siyu Liu, Kailang Wu and Chenglian Zhu. Author Siyu Liu should instead of having affiliation 1, have \u201cState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China\u201d. Author Kailang Wu should instead of affiliation 1, have \u201cState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China\u201d. Author Chengliang Zhu should, instead of affiliation 2 have \u201cDepartment of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China\u201d. The corrected affiliations appear above.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Sleep is an essential biological requirement for human life, alongside food, water, and air. Therefore, it is not surprising that insufficient sleep, in terms of both quantity and quality, may disrupt cognitive and physical performance, quality of life and health. Sleep is compromised in many cardiological, neurological, psychiatric, metabolic, pneumological, and oncological diseases, but it is also well known that sleep disorders significantly increase the risk of cardiovascular, neurological, and oncologic disease, and that they can deeply modify the outcome of coexisting medical conditions ,2,3,4. TIn the light of the reciprocal relationship between sleep and health, it appears crucial that pulmonologists, endocrinologists, neurologists, cardiologists, otolaryngologists, psychiatrists, psychologists, pediatricians, dentists, and family medicine practitioners evaluate sleep quantity and quality in their daily activities.Brain Sciences, entitled \u201cMultidisciplinary Aspects of Sleep Medicine\u201d, was to provide additional insight into this topic, including relevant studies from experts in the field.Following this perspective, the goal of this Special Issue of Sleep bruxism is a common behavior, with a prevalence estimated in 13% of the general population, characterized by pain in the masticatory muscles and/or tooth wear. In a preliminary study, Wieckiewicz et al. found a Obstructive sleep apnea (OSA) is a multifactorial disease that is an increasing social and health problem occurring in about 3\u201310% of general population. It is characterized by recurrent breathing pauses due to the collapse of the upper airways and represents an independent risk factor for hypertension, ischemic heart disease, strokes, heart failure, atrial fibrillation, sudden cardiac death, cancer, and cognitive disorders. Urbanik et al. analyzedIn the same area, Macek et al. assessedIn industrialized countries, professionally active populations frequently have reduced sleep that may lead to daytime sleepiness, cognitive deficits, and impaired response of the stress-related activities of the hypothalamic\u2013pituitary axis and the autonomic nervous system. Gomez-Merino and colleagues , in theiIn the last decade, several studies evaluated the physiological and pharmacological properties of melatonin and its crucial role in regulating the sleep/wake rhythm. Biggio et al. , in theiThe content of this Special Issue may represent a preliminary, though still meaningful, contribution to the scientific evidence. Many research efforts in sleep medicine are moving towards novel approaches and new advancements for the diagnosis and treatment of sleep disorders. Relevant progress in the identification of the sleep functions and the reciprocal relationships between sleep disorders and systemic diseases may improve quality of life as well as the effectiveness of health care."} +{"text": "Instead of \u201cRehabilitation Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China\u201d, it should be \u201cCheeloo College of Medicine, Shandong University, Jinan, Shandong, China.\u201dIn the published article, there was an error in affiliation for Hao Zhang. Instead of \u201cHao ZhangThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "A 3-year-old girl presented to our outpatient clinic with a bee sting on her neck. One hour earlier, a honeybee had landed on her neck, and she had swatted it, resulting in a painful sting. The patient did not exhibit any symptoms of fever, cough, cold, nausea, vomiting, breathlessness, chest pain, palpitations, blackouts, or loss of consciousness, but she did report pain in the area where she was stung. On examination, we observed a foreign body on the right side of the patient\u2019s neck . DermoscHymenoptera stings are common and painful envenomations that lead to an annual average of 62 deaths in the United States.Although honeybees are notorious for leaving their stingers in the victim\u2019s skin, other members of the Hymenoptera order may also leave a stinger behind."} +{"text": "Nutrition is essential to sustaining the quality of life and a fundamental right of all people . Yet, maHealthcare Special Issue, \u201cNutrition and Public Health 2.0\u201d, brings together research from scholars of different disciplines representing various regions of the world to understand achievements and current issues in nutrition and public health, including research, practice, policy, and communication across the lifespan. The articles selected are centered on two public health nutrition concepts: nutrition security and nutrition equitability.The Nutrition security ensures that individuals, families, and countries have physical, social, and economic access to sufficient, affordable, safe, and nutritious food that meets their dietary needs and preferences for an active and healthy life ,5. NutriNutrition equitability is an emergent concept that addresses the food system stakeholders and holds the stakeholders accountable to ensure accessibility and affordability of sufficient nutrition regardless of individuals\u2019 social, environmental, and economic positions ,10. ThisIn summary, the 16 articles in the Public Health and Nutrition 2.0 Special Issue document that to achieve population-level nutritional well-being, nutrition equitability, and security is essen"} +{"text": "Viruses, we showcase some of the fascinating and diverse virology being undertaken in Canada that was presented at the 4th Symposium of the Canadian Society for Virology 2022 [Viruses, we accrued five manuscripts to highlight research that focuses on human, animal, and bacterial viruses.In this Special Issue of ogy 2022 ,2,3,4,5.Beginning with work by Hare et al. , this teYousefi et al. investigNext, turning towards Mpox , we highlight the important proof-of-principle work by Noyce et al. . Here, rAlong similar lines in vaccine research, Aubrey et al. highlighListeria monocytogenes, a bacterial pathogen that has been linked with prior contaminations of processed sandwich meats. Their team reports on the importance of bacteriophage stability under various stressors, including desiccation, elevated temperature, and low pH, mimicking various food preparation environments, and uses these conditions to both quantify those effects and select for stress-resistant bacteriophages. Their work may have broader applications to other food industry phages as this field continues to evolve.Finally, Gomez et al. describeOverall, the collection of these manuscripts is, of course, only a small sampling of the great work being carried out by Canadian virologists and highlights a diverse range of studies, from fundamental understanding to practical applications to therapeutics development."} +{"text": "After this article was published, similarities were noted between this article and submissions by other research groups which call into question the validity and provenance of the reported results. In addition, during editorial follow-up, a number of data extraction errors were found, meaning some of the conclusions are no longer supported.PLOS ONE cannot stand by the reliability of the reported research, and the PLOS ONE Editors retract this article [In light of these issues, article .JZ did not respond to the final editorial decision. CM, AX, KZ, ZQ, XL, CL, YH, WC, CZ, YL, SS, ZW, and BL either did not respond directly or could not be reached."} +{"text": "Archives of Endocrinology and Metabolism (AE&M) are completing its first year. Despite its name in English and the mandatory use of this language for all articles, the former \u201cArquivos Brasileiros de Endocrinologia e Metabologia\u201d remains the official Journal of the Brazilian Society of Endocrinology and Metabolism. I believe that such change will progressively increase the knowledge and interest of endocrinologists around the word on our journal, which, without losing its Brazilian origin and identity, will become more and more an international publication. Consequently its impact factor, unavailable during two years due to its name change, is expected to augment, leading to the increase of submissions of good original basic, translational and clinical research, in a healthy vicious cycle. In order to pursue the increase of the impact factor, original and review papers should be privileged, in detriment of case reports. As a matter of fact, many medical journals increased its impact factor restricting the acceptance of case reports. On the other hand, many journals are dealing specifically with this kind of medical article.The During 2015, 416 manuscripts have been submitted to AE&M. From them, 71.4% were original research, and the remainder consisted of case reports (18%), review articles (5.5%), brief reports (4.6%), letter to the editor (0.2%), and consensus statement (0.2%). From the total of submitted manuscripts, 306 came to a decision, and 79 have been accepted for publication (26%).Regarding the number of manuscripts per country, Brazil submitted 146, Turkey 61, China 16, India 11, Iran 10, Argentina 9, Portugal 8, Italy 7, Romania 5, and Egypt 4. Additionally, the following countries also submitted articles: Algeria, Bulgaria, Chile, Colombia, Croatia, Cyprus, Greece, Hungary, Mexico, Nigeria, Pakistan, Poland, Saudi Arabia, Serbia, Slovakia, Spain, Taiwan, Tunisia, USA, and Venezuela.In this second year of my task as Editor-in-Chief of the AE&M, I intend to strengthen the relationship with colleagues of other countries, asking for reviews and mini-reviews. For this purpose I expect to count on the international editorial board of our journal.Last but not least, I would like to acknowledge and warmly thank all my Associate Editors for their outstanding collaboration, as well as the Brazilian and International reviewers for their time and expertise, selecting manuscripts which enriched the quality of our AE&M."} +{"text": "This study explores the trend of urolithiasis in various countries and categorizes the countries in terms of how their urolithiasis incidence rate has changed over time.The incidence rate of urolithiasis in 204 countries from 1990 to 2019, extracted from the Global Burden of Disease study, has been analyzed.p-value\u2009<\u2009.05). Also, African regions revealed significant increasing trends over time . The outstanding findings in cluster analysis showed that Afghanistan, Andorra, and Comoros had the most decreasing trend in urolithiasis rates over time . Cuba, Cyprus, Czechia, the Democratic People's Republic of Korea, Denmark, and Djibouti were in the next rank in terms of decreasing rate . In addition, urolithiasis rates in Congo, Eswatini, Gabon, and Grenada have the most increasing trend .According to the results, all regions had experienced an increasing trend in urolithiasis rate, except for Eastern Europe, Central Europe, and Southeast Asia regions . Moreover, the Caribbean region had the highest increasing trend of urolithiasis rates, and Central Asia was in the next rank (increasing rate of 48.3 and 34.3 per 100,000, respectively, The trend of urolithiasis rates was significantly increased in most countries, and Congo, Eswatini, Gabon, and Grenada had the highest trend among others. Also, Afghanistan, Andorra, and Comoros revealed the most decreasing rates, and the trend has dropped remarkably in several other countries. Urolithiasis, defined as the concentration of minerals in renal calyces and pelvic, is a common and painful urological condition with a significant disease burden worldwide. The prevalence of urolithiasis and, as a result, kidney stone burden has been increasing significantly in recent years all over the world, especially in developed countries , 2. UrolTo a better understanding of the global epidemiology of urolithiasis and its implications for public health and clinical practice, this study categorizes the countries into different groups based on how their urolithiasis incidence rate has changed over time. This study presents a longitudinal analysis through latent growth modeling on urolithiasis rates in 204 countries and territories. The analytical approach used in the present study is different from previous published studies and is a powerful tool for analyzing longitudinal data, as it can capture the dynamic and complex patterns of change over time and reveal the underlying structure and heterogeneity of the data.Data for incidence rates of urolithiasis (per 100000 persons) in 204 countries and territories were derived from the GBD study . The infwww.statmodel.com).The incidence rates of urolithiasis in each region were described with mean and standard deviation and appropriate plots. The response variable in this study is urolithiasis\u2019s incidence rates, which were modeled using the Latent Growth model to assess the trend in IMHE regions. Also, Growth mixture models (GMM) were applied, and countries were classified into subgroups in which samples within each subgroup followed similar trends over time. GMM is an advanced statistical approach used for trend analysis, and it can take into account heterogeneity in trends among countries. Therefore, using GMM, subgroups of countries are specified, in which countries within each group have similar trends of urolithiasis rates over the period of study. The coefficients of this model, intercept and slope, are interoperated as the overall mean level of the initial outcome and the average rate of outcome change over time, respectively. Statistical analysis was done using M-plus software, version 6.12 .We also applied the LGM to assess the trend of urolithiasis rates in each region separately. According to the obtained Beta from LGM, all regions had experienced an increasing trend of urolithiasis rate, except for Eastern Europe, Central Europe, and Southeast Asia region, which had a negative coefficient. According to the results, countries in Eastern Europe had a mean decrease of 71.4 per 100,000 from the year 1994 to 2019. In the next rank, Central Europe countries reveal a mean reduction of 56.2 per 100,000 during the study period. Moreover, the results show that the Caribbean region had the highest increasing trend of urolithiasis rates . The countries in Central Asia were in the next rank with a growing trend of 34.3 per 100000 people. African regions, including Western Sub-Saharan Africa , North Africa and Middle East , Central Sub-Saharan Africa , Eastern Sub-Saharan Africa and Southern Sub-Saharan Africa revealed significant increasing trends over time . Also, countries in cluster 2, including Cuba, Cyprus, Czechia, Democratic People's Republic of Korea, Denmark, and Djibouti, have an initial rate of urolithiasis of 4808.6 per 100000 in 1990, and they have a decreasing trend with a slope of about -92.3 until 2019 . Azerbaijan, Brazil, Brunei Darussalam, Canada, Chile, Ethiopia, Greece, Iceland, and Iran entered in class 3, had the next rank in terms of decreasing rate . Countries in clusters 1, 2, and 3 can be defined as having a sharp, moderate, and slow decreasing trend in urolithiasis rates over time, respectively.The intercept coefficients represent the estimated overall mean level of the initial urolithiasis rate in each cluster, and the slopes show the average urolithiasis rate change over time. A positive and negative slope reveals that the rate had an increasing and decreasing trend over time, respectively. For instance, the estimates for the first cluster reveal that the initial rate of urolithiasis in the countries including this cluster, Afghanistan, Andorra, and Comoros, has been 2330.26 per 100000 in 1990, and it has a decreasing trend with a slope of -128.2 until 2019, every two years . Finally, countries in cluster 7, Congo, Eswatini, Gabon, and Grenada, have experienced a sharp growing trend of urolithiasis rate during this period of time . The colored map in Fig.\u00a0In addition, countries in classes 4 and 5 have a slowly increasing trend of urolithiasis over time until 2019. urolithiasis rates in countries included in cluster number 6 have a moderate increasing trend . Congo, Eswatini, Gabon, and Grenada have the sharpest increasing rates of urolithiasis. In the next rank, Bahrain, Bosnia and Herzegovina, Bulgaria, Chad, Cook Islands, Costa Rica, Croatia, Guatemala, Honduras, Kazakhstan, Lebanon, Liberia, Morocco, and Yemen had the most increasing rate of urolithiasis. Other countries not mentioned so far have also seen an increase in the Urolithiasis incidence rate. These findings are in line with other studies , 26. It It is notable that gender, race, and median age of the population are important factors that can influence the prevalence of urolithiasis in different countries.According to a recent review, the prevalence of kidney stones is increasing and historically more common in males . HoweverThere is evidence that urolithiasis varies among different racial and ethnic groups . TraditiUrolithiasis is known to increase with age , 33. HowFinally, it is notable that due to the availability of new and more accurate diagnostic tools contributing to an increased diagnosis, asymptomatic stones are more detected due to the more frequent use of high-resolution imaging techniques , 34. On However, the GBD is a comprehensive and systematic effort to estimate the burden of diseases and injuries for 204 countries and territories from 1990 to 2019, it also faces several challenges and uncertainties in the data collection which can introduce potential biases and limitations in the results. One of the main challenges is the variation in healthcare infrastructure, diagnosis practices, and data reporting among different countries. These factors can affect the accuracy and comparability of urolithiasis incidence rates across countries. For example, some countries may have more advanced diagnostic tools or more frequent screening programs than others, which can lead to higher detection rates of urolithiasis. Similarly, some countries may have more reliable and comprehensive data sources or more consistent definitions and classifications of urolithiasis than others, which can influence the quality and comparability of the data. These factors can introduce bias in the data, so caution is advised in interpreting and comparing the results across countries and over time.Globally, the incidence rate of urolithiasis has increased during 1990\u20132019, with various patterns in countries and regions.\u00a0The trend of urolithiasis rates was significantly increased in most countries, and Congo, Eswatini, Gabon, and Grenada had the highest trend among others. Also, the trend has dropped remarkably in several other countries. Afghanistan, Andorra, and Comoros revealed the most decreasing rates. Overall, while the high economic and health burden of urolithiasis, its rate does not seem to have dropped remarkably in most countries. Therefore, nowadays, when lifestyle leads people to this disease, it is important to implement comprehensive preventive programs that consider controllable risks, including nutritional factors, nutritional deficiencies, lifestyle factors, etc."} +{"text": "Cost-effectiveness of adding empagliflozin to the standard therapy for Heart Failure with Preserved Ejection Fraction from the perspective of healthcare systems in China by Jiang Y and Xie J. (2022) Front. Cardiovasc. Med. 9:946399. doi: 10.3389/fcvm.2022.946399A Corrigendum on In the published article, there was an error in the affiliation. Instead of \u201cDepartment of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China\u201d, it should be \u201cDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The human body consists of its own cells, but also of microorganisms that are found both inside and outside the human body .Commensal microorganisms are of fundamental importance to the host, as they perform important tasks, such as contributing to host health, counteracting pathogenic bacteria, contributing to the regulation of host homeostasis and balance, and modulating the immune response .The oral microbiota is an important constituent of the human microbiota, with a fundamental role in human health. It is a complex matter, primarily because of the conformation of the oral cavity, which appears to be formed by a set of different ecological niches , with very different microbiological habitats that expand and vary greatly in pathology .http://www.homd.org, accessed on 21 September 2023) [The main phyla present in the oral cavity and constituting approximately 94% of the oral microbiome are Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes, and Fusobacteria. The remaining 6% of the bacterial phyla consist of Saccharibacteria, Synergistetes, SR1, Gracilibacteria, Chlamydia, Chloroflexi, Tenericutes, and Chlorobi 1, etc. .Several authors report that in the first 1,000 days after conception, a eubiosis framework is of fundamental importance for the development and maturation of the immune system, with even long-term effects on the health of the unborn child. An altered microbiota is in fact, according to multiple investigations, a predisposing factor for the onset of respiratory, allergic, immune, and metabolic diseases .In addition, several aids have been proposed to restore or prevent dysbiosis, including probiotics , the terOzone, which is widely used in medicine, also has a valid application for modifying the oral microbiota, in particular to eliminate bacteria and fungi, inactivate viruses, and control bleeding. .In conclusion, the aim of this research topic is to provide readers with up-to-date data on the association between dysbiosis of the oral microbiota and systemic conditions ,30. We h"} +{"text": "The ACIP recommendations were adopted by the CDC Director on June 27, 2023, and are official. The recommendations, underlying evidence and rationale, and clinical guidance are available (Supplementary Report,"} +{"text": "Nature 10.1038/s41586-023-06440-7 Published online 23 August 2023Correction to: In the version of the article initially published, Stanislaw Miscicki\u2019s name incorrectly appeared as Miscicki Stanislaw. Additionally, the affiliation for Thomas T. Ibanez has been updated to \u201cAMAP, University of Montpellier, CIRAD, CNRS, INRAE, IRD, Montpellier, France\u201d, and the second affiliation for Sharif A. Mukul has been updated to \u201cDepartment of Environment and Development Studies, United International University, Dhaka, Bangladesh\u201d. The corrections have been made to the HTML and PDF versions of the article."} +{"text": "In \u201cDeep Learning With Chest Radiographs for Making Prognoses in Patients With COVID-19: Retrospective Cohort Study\u201d the authors made one amendment. The affiliation for co-author Soo-Youn Ham was listed as:Department of Radiology, Kangbuk Samsung Hospital, Seoul, Korea, Republic ofAnd will be changed to read as follows:Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic ofThe correction will appear in the online version of the paper on the JMIR Publications website on August 23, 2023 together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Saeed et al.\u2019s 2021 study examined the impact of Coronavirus disease (COVID-19) on anxiety and depression among students.We interviewed 34 first-to third-year undergraduate Japanese students, and asked them \u201cwhat are the factors that made you feel stressed in your studies or private school life?\u201d Students\u2019 interviews were recorded and transcribed. The transcribed data was coded, and similar contents were classified into five mutually exclusive categories with qualitative content analysis as follows: 1. Transition to university life; 2. Examinations; 3. Attendance and homework; 4. Extracurricular activities; 5. Social and human relationships . COVID-13Ansari et al. (2022) published data on stress and anxiety in medical and non-medical students; using a quantitative cross-sectional online survey, they found that the effect of social distancing and online learning weakened the students\u2019 relationships with their family, their peers, and the faculty,We strongly agree with the conclusion of Ansari et al.\u2019s study that social connection/support should be maintained as much as possible even in a virtual settingMM: Research concept, design of the study, literature review, data collection, data analysis, data interpretation, preparation of initial draft, approval of final draft, and guarantor of the manuscript.SJ: Research concept, design of the study, literature review, data collection, data analysis, data interpretation, revision of initial draft, approval of final draft, and corresponding author of the manuscript.AT: Research concept, design of the study, literature review, data interpretation, revision of initial draft, and approval of final draft.KM: Research concept, design of the study, prior literature review, data interpretation, revision of initial draft, and approval of final draft."} +{"text": "Generally, to achieve success in endodontics, it is essential to perform all stages of treatment with cautiousness and excellence ,2.The first stage, one of the most important, is the diagnosis. At this stage, only with the help of modern technologies is it possible to carefully examine the fundamental problems of the tooth and organise a correct treatment plan ,4. For eAmong the fundamental equipment for an effective diagnosis, we have three-dimensional radiology, the 3D CBCT .Moreover, utilising this equipment, we can achieve a series of advantages; for instance, precise analysis of internal and external resorptions, detection of pathologies of the maxillary sinus of odontogenic origin, visualisation of root morphology, observation of small lateral or periapical lesions, precise control of healings, identification of fractures ,7. All oFurthermore, modern 3D CBCT equipment can carry out targeted scans of small dimensions, only on the tooth or a few teeth to be analysed. Consequently, the radiation doses decrease, avoiding exposing the patient to excessive doses. In addition to radiology, in the diagnostic phase, it is essential to analyse the vitality of the teeth, any cracks, the periodontal status, etc. ,9,10.Only after having performed a correct diagnosis is it practicable to proceed with the subsequent stages of endodontic treatment: isolation of the operating field, access cavity, mechanical shaping, chemical cleaning, obturation, and finally, a suitable restoration ,13,14,15Recent approaches and devices are available that allow a general dentist or a recent graduate to have safe and reproducible treatments.The latest generation of rotating files is highly flexible and simple; it comprises effective cleaning techniques and modern obturation techniques that use the new biosealers ,23,24,25In conclusion, each stage should be performed excellently using modern technologies and protocols to achieve success."} +{"text": "Over the course of civilization, humans have increasingly expanded their freedom to live a better life. In comparison with the primitive society, our modern society has many more choices of life-supporting resources, such as year-round food supply, permanent shelters, diverse energy sources, and effective preventive and curing medicine. However, our society is currently still heavily relying on the resources provided by Mother Nature, which cannot meet the future global needs in terms of both quantity and quality under the pressure of population growth, natural resource reduction, and environmental deterioration. For example, the food sources originating from plants, animals, or microbes do not have the nutrition balance for optimal human health \u20133. ClBiodesign in living organisms deals with the structure of the particular organism and the interactions between the biomolecules encoded in their genomes. In the broadest sense, biodesign is concerned with the nature and properties of the information required to create biological behavior at the ecological, organism, cellular, organelle, and molecular levels and how biological systems interface with the environment and devices. The explosion of omics data , the rapid advance in computational modeling and machine learning, the reduced cost of omics data generation and analysis and DNA/RNA and protein synthesis, and the disruptive genome editing technology based on CRISPR- Cas (CRISPR-associated) systems have accelerated the evolution of biodesign as a next-generation discipline of biology, as best reflected by a rapid increase in the number of publications related to biodesign since a decade ago Figure. As a cWith unlimited potential in fundamental research, broad practical applications, and ever-increasing amount of R&D funding support from government agencies, industries, and government/industry consortia around the world, biodesign is growing into a new interdisciplinary field that integrates a wide range of research areas, including molecular biology, genetics, biochemistry, genomics, chemical engineering, computational biology, bioinformatics, synthetic biology, systems biology, physiology, ecology, breeding, medical science, animal science, microbiology, crop science, horticulture, and forestry. To embrace the promise of this fast-growing research discipline, this journal was launched to advance both fundamental and applied research, foster multidisciplinary collaboration, and promote dissemination of scientific information and knowledge in the field of biosystems design. This new journal will emphasize the rational or automated design of engineered organisms to address global challenges in health, agriculture, bioenergy, and the environment. It will promote research, with the increasing sophistication and greater social responsibility, on the predictable conduct of (1) engineered biological parts in an exogenous genomic context, (2) engineered part assemblies in an exogenous compartment context, (3) engineered assemblies in an exogenous cell, (4) engineered cells in an exogenous tissue, and (5) engineered tissues in an exogenous organism.de novoorganism biodesign; and (3) social responsibility dimension: biodesign security and ethics scientific dimension: biodesign theory, principles, methodology, tools, and applications; 2) organismal dimension: animal, human, microbial, plant, and organismAs a vigorously peer-reviewed, open-access online-only journal, it is dedicated to rapid, efficient, and free worldwide dissemination of scientific discoveries, technological advancements, and social responsibilities in the format of research articles, reviews, editorials, and perspectives. We are honored and humbled to serve the biodesign community as the founding editors-in-chief and executive editor and are extremely grateful to highly reputable experts to serve as associate editors. This journal welcomes high-quality manuscripts from researchers around the world. We hope that this journal will grow fast and healthy to become a leading journal in the field of biodesign through collective efforts of the editorial board, authors, reviewers, and readers."} +{"text": "Parent\u2013child interaction therapy (PCIT) is considered to be an effective intervention for children aged 2\u20137 years with conduct problems. PCIT research has been conducted for approximately 50 years; however, an analysis of general research patterns has not been published. In this context, the present study outlines a bibliometric analysis of scientific collaborations, prevalence across locations on the basis of countries and organizations, leading researchers, and trends within PCIT research. Findings demonstrate that PCIT is an area in which international scientific collaborations are intense and current, and collaborations continue to be formed around the world. Additionally, results indicate that dissemination of intercultural PCIT adaptations are continuous. DevelopResearchers have investigated PCIT as an effective treatment for a variety of emotional and behavioral concerns such as childhood depression , ADHD C, autism Many studies examining PCIT as a treatment for emotional and behavioral concerns have found promising results. For instance, PCIT has been found to be an effective intervention for oppositional defiant disorder (ODD). ODD is often characterized by a child\u2019s lack of respect for authority figures, and a child with a diagnosis of ODD may exhibit behaviors such as breaking the rules, tantrumming, arguing with adults, displaying provocative behaviors, and acting stubborn . Bagner Additionally, a review of PCIT outcome studies measuring the effectiveness of PCIT in the rehabilitation of ADHD, one of the most common behavioral problems in children aged 2\u20137\u2009years, reported that PCIT is a very effective approach in reducing ADHD symptoms . More reThere are also studies demonstrating that PCIT remains effective for children who have experienced trauma. Research has found that PCIT and PCIT-based interventions are an effective approach in the rehabilitation of children who have been physically and emotionally abused, and thus, PCIT can prevent disruptive behaviors that may occur later in life . A studyHowever, researchers have noted the importance of treatment completion in family outcomes , and PCIIn the international literature, there are many clinical case studies, single-subject design studies, and randomized controlled trials using PCIT as a treatment for disruptive behavior of children with autism spectrum disorder . StudiesWhat is the distribution of publications on PCIT by years?What is the distribution of publications on PCIT according to Web of Science categories?What is the distribution of publications on PCIT according to the publisher?What is the distribution of publications on PCIT according to Web of Science index?What is the distribution of publications on PCIT by country?What is the distribution of publications on PCIT by organization?What is the distribution of authors publishing on PCIT?What is the distribution of journals in which PCIT studies are published?What is the distribution of citations on PCIT studies?What are the scientific collaborations and research trends within PCIT research?The purpose of the present study is to identify scientific collaborations within the PCIT subject area, examine the prevalence of PCIT studies across locations on the basis of countries and organizations, identify leading researchers, and to reveal trends within the PCIT research through a bibliometric analysis. In this context, the research questions to be answered are as follows.2.The present study focuses on examining publications on PCIT through bibliometric analysis.2.1.Firstly, the bibliometric data of the data sources were searched. In this context, the Web of Science (WoS), the most prominent database of international scientific literature was sear2.2.Data for the present study was taken directly from WoS. Full data records and cited references were downloaded from the WoS Export menu in a tab-delimited file format. Obtained data were analyzed bibliometrically. Depending on the purpose of determining the intellectual structure and trends of the international literature, researchers may use bibliometric analysis when the scope of the review is wide and the data sources are too large for manual review . Distanc3.3.1.The number of publications in the field of PCIT provides important findings in terms of the development processes of the related field. In this context, the distribution of publications related to PCIT by year is presented in According to the WoS database records, PCIT studies were first published in 1970. While in the beginning PCIT publications ranged between 1 to 5 publications per year, 1\u201311 publications per year were detected between 1981 and 2003, 11\u201330 publications per year were detected between 2004 and 2013, and 23\u201356 publications per year were detected between 2014 and 2022.According to these categories of dates, each covering a range of 13\u2009years, 8.08% of PCIT studies were published between 1970 and 1982, an additional 8.08% were published between 1983 and 1995, 18.82% were published between 1996 and 2009, and 65.02% were published between 2010 and 2022. In this context, considering the number of early publications and the number of publications in recent years, it can be determined that PCIT studies have been published with increasing intensity for 52\u2009years.3.2.According to the WoS database records, PCIT studies were found to be most prominent in WoS categories of Psychology Developmental, Psychology Clinical, Psychiatry, Family Studies, Social Work, Pediatrics, Psychology Multidisciplinary, Rehabilitation, Linguistics, Education Special, Education Educational Research, Psychology, Public Environmental Occupational Health, Psychology Social, Psychology Educational, Sociology, Language Linguistics, Communication, Environmental Sciences, Audiology Speech Language Pathology, Behavioral Sciences, Psychology Experimental, Clinical Neurology, Computer Science Interdisciplinary Applications, and Neurosciences, respectively .3.3.According to WoS database records, Elsevier, Taylor & Francis, Springer Nature, Sage, Wiley, APA, MPDI, Oxford University Press, Cambridge University Press, Lippincott Williams & Wilkins, Amer Speech-Language-Hearing Assoc, Haworth Press Inc., British Psychological Soc, and Educational Publishing Foundation-American Psychological Association publish PCIT literature the most frequently .3.4.According to 3.5.In the analysis carried out to determine international collaborations regarding PCIT studies, co-authorship was used as the type of analysis, countries as the unit of analysis, the minimum number of documents by country was determined as 2, and the minimum number of citations by country was determined as 2. As a result of the analysis examining over 52 countries, the countries from where PCIT studies were published were found as 20 items and 9 clusters. During the visualization process, the total link strength (tls) was used as the weight scale of each item.The first cluster, shown in According to the results of the analysis to determine the central country, it can be said that the United States leads all countries in published PCIT studies , and theThe result of the analysis conducted to determine the distribution and collaborations among organizations from where PCIT studies are published is presented in When According to The result of the analysis examining researchers who are in scientific collaboration and relatively central positions among PCIT studies is presented in According to When The mapping of the analysis of journals that have published PCIT research is given in Analysis results examining the journals that have published PCIT research are shown in When In addition, the citation network among published PCIT researchers was analyzed with the researcher\u2019s unit and presented in The results of the analysis to determine the citation network for PCIT researchers are shown in When In a co-occurrence analysis of publications within the scope of the study, the author keywords were determined as the analysis unit. In this context, it is aimed to map the whole conceptualization by reducing the minimum number of common keywords to 2 in the study. Based on the 2-word limit, 219 words were mapped from the data set containing 991 keywords. However, as in other mappings, there are repetitive keywords . These are excluded in the visualizations. The visualization is based on occurrences as the weighting criterion.According to Items in the second cluster are abuse , addiction , aggression , cancer , child abuse , child neglect , communication , development , domestic violence , family therapy , joint attention , language , language acquisition , neglect , parent , relationship , retention , and synchrony . Items in the third cluster are adverse child experiences , case report , case study , childhood obesity , low-income , obesity , obesity prevention , parenting training program , parent\u2013child interaction therapy , parent\u2013child relationship , parenting , self-regulation , social skills , telehealth , and traumatic brain injury . Items in the fourth cluster are adoption , attachment , barriers , behavioral parenting training , childhood conduct problems , consultation , dissemination , evidence based treatment , facilitators , implementation , parent management training , therapist training , time-out , and training . Items in the fifth cluster are child abuse prevention , COVID-19 , foster care , mental health , mobile device , mobile phone , parenting intervention , positive parenting skills , preterm birth , RCT , stress , and translational research . Items in the sixth cluster are behavior problems , case series , child disruptive behavior , community mental health , engagement , natural helper , preschool children , single subject design , stuttering , therapy , and treatment outcomes . Items in the seventh cluster are adaptations , child behavior problems , child welfare , community intervention , cost-effectiveness , effectiveness , efficacy , meta-analysis , systematic review , and treatment outcome . Items in the eighth cluster are conversation analysis , emotion coaching , emotion regulation , emotion socialization , externalizing behavior , longitudinal , reflective functioning , socialization , television , and toddlers . Items in the ninth cluster are child development , cognitive development , developmental delay , early intervention , language development , maternal depression , parenting stress , and preschoolers . Items in the tenth cluster are attrition , disruptive behavior , dropout , follow-up , home-based treatment , maintenance , outcome , and treatment . Items in the eleventh cluster are child behavior , child maltreatment , observation , preschool depression , prevention , psychometric properties , randomize controlled trial , and sensitivity . Items in the twelfth cluster are acceptance and commitment therapy , anxiety , behavior therapy , child anxiety , oppositional defiant disorder , and selective mutism . Items in the thirteenth cluster are down syndrome , parent\u2013child interaction , pragmatic functions , repetition , sequential analysis , temperament , and young children . Items in the fourteenth cluster are attention deficit/hyperactivity disorder , behavior intervention , callous-unemotional traits , conduct problem , families , internet-based treatment , and trauma . Items in the fifteenth cluster are adherence , brief treatment , competence , externalizing behavior problem , homework , and treatment fidelity . Items in the sixteenth cluster are alexithymia , attention deficit , autism spectrum disorder , hyperactivity disorder , reliability , and validity . The item in the seventeenth cluster is motivation and the item in the eighteenth cluster is behavior observations .When Based on the links listed, it can be interpreted that PCIT has a parent training quality and is considered a short-term approach. In addition, adaptation and dissemination studies of PCIT continue around the world, the effectiveness of the studies beyond adaptation is examined, the therapy has an adaptive structure, and therapist acceptance is an important item. It is clear that the effectiveness of PCIT on child behavior and adjustment problems has been studied. The effect of this intervention on children, as well as the effect of this intervention on parental stress and emotion regulation, has been examined. In addition, it is seen that PCIT has been examined in home-based and web-based formats in recent years . Thus, it can be interpreted that PCIT has a structure which may be transferable to technology and its application areas have expanded.4.n\u2009=\u200923), New Zealand (n\u2009=\u20097), and Australia (n\u2009=\u200944) have gained momentum in PCIT studies , publication year, language, etc. will impact the availability of bibliometric data. It is considered a limitation of the study that the keywords of (\u201cparent child interaction\u201d) or (\u201cparent\u2013child interaction\u201d) or (\u201cparent child interaction therapy\u201d) or (\u201cparent\u2013child interaction therapy\u201d) or (\u201cpcit\u201d) used during the search of data sources are used in English. This may limit the analysis of publications indexed in the WoS database in other languages. Given the use of VOSviewer for the analyses in this study, another limitation is the method for dealing with repetition of items . Errors may be apparent in the names of universities, the included researchers, the topics, and the citations based on the search parameters. Yet, strengths of the current bibliometric analysis include visualizing data such as prominent keywords, countries, universities, researchers, citations, and research topics which reveals general patterns associated with the historical dissemination of PCIT.The fact that the keyword used in the research process is searched only in the title is a limitation of the study, as some researchers may publish PCIT research without including PCIT in the title . Another6.Based on the analysis of bibliometric data of PCIT publications retrieved from the WoS database, it was concluded that PCIT studies have continued to increase since 1970. According to the classifications created, each covering a range of 13\u2009years, the highest rate of publications occurred between 2010 and 2022 (65%). In conclusion, these findings demonstrate that PCIT is a current research topic for the intervention of disruptive behavior problems and other various emotional, behavioral, and physical health concerns observed in children from various cultures.When the studies were classified according to the WoS categories, it was concluded that the five most popular WoS categories in PCIT research were Psychology Developmental, Psychology Clinical, Psychiatry, Family Studies, and Social Work. Similarly, the five most frequent publishers of PCIT studies include Elsevier, Taylor & Francis, Springer Nature, Sage, and Wiley. In terms of WoS publication index categories, it was concluded that the majority of the publications (85%) were in the SSCI index. While most of the published PCIT studies are carried out in the United States, scientific collaborations have recently been established between Australia, New Zealand, Denmark, Netherlands, Taiwan, and Iran. Furthermore, the central organizations where published PCIT studies are conducted include the Univ Florida, Univ Oklahoma, West Virginia University, Griffith Univ, Michigan State Univ, Univ Calif Davis, Univ Massachusetts Dartmouth, Univ Calif Riverside, Florida State Univ, New York Univ, Univ Sydney, Univ New South Wales, and Texas Tech Univ. Developmental Psychology, Topics in Early Childhood Special Education, Journal of Abnormal Child Psychology, Child & Family Behavior Therapy, and Journal of Consulting and Clinical Psychology are the journals in which PCIT studies are published most frequently. Sheila M. Eyberg, Melanie J. Zimmer-Gembeck, Beverly W. Funderburk, Rae Thomas, Larissa N. Niec, Cheryl B. McNeil, Daniel M. Bagner, Miya L. Barnett, Jonathan S. Comer, Amy D. Herschell, Susan G. Timmer, Eva R. Kimonis, Mark Chaffin, Kathleen Armstrong, Anthony J. Urquiza, Nancy M. Zebell, Lisa M. Ware, G. Mahoney, and H. Lyton are prominent researchers based on citations. The most frequently used keywords for PCIT studies are PCIT, dissemination, implementation, treatment, effectiveness, child welfare, behavior problem, autism spectrum disorder, emotion regulation, early intervention, child maltreatment, treatment, early intervention, oppositional defiant disorder, joint attention, language development, developmental delay, barriers, implementation, autism spectrum disorder, mobile phone, home-based treatment, emotional coaching, natural helper, telehealth, obesity, obesity prevention, addiction, parental responsiveness, preschool depression, reflective functioning, emotion regulation, and time-out. While some keywords are related to the structure of PCIT , some of them are related to application areas .Although PCIT is a subject area in which international scientific collaborations are intense and current, it is also an area in which collaborations continue to be formed around the world. At this point, it can be determined that intercultural adaptations of PCIT, an effective approach for treating emotional and behavioral problem areas experienced by children and their families with both typical development and developmental delay problems, are continuous.SU: conceptualization, methodology, software, formal analysis, writing \u2013 original draft preparation, and visualization. \u0130S, CM, and EV: validation. \u0130S and SU: investigation. SU, \u0130S, EV, and CM: writing \u2013 review and editing. \u0130S and CM: supervision and project administration. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Editorial: Over the last few decades, the scientific community has recognized the enormous potential of bioactive dietary nutrients/components in the management and prevention of cancer. Based on the fact that bioactive dietary nutrients and molecules modulate the key deregulated signaling pathways in cancers, including proliferation, apoptosis, cell cycle progression, migration, invasion, and angiogenesis ,2,3, it"} +{"text": "In the published article, there was an error regarding affiliation 1. Affiliation 1 was published as: Clinical Laboratory, Dongyang People\u2019s Hospital, Jinhua, Zhejiang, China. The correct affiliation is: Department of Clinical Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Worldwide, several food-based dietary guidelines, with diverse food-grouping methods in various countries, have been developed to maintain and promote public health. However, standardized international food-grouping methods are scarce. In this study, we used two-dimensional mapping to classify foods based on their nutrient composition. The Standard Tables of Food Composition in Japan were used for mapping with a novel technique\u2014t-distributed stochastic neighbor embedding\u2014to visualize high-dimensional data. The mapping results showed that most foods formed food group-based clusters in the Standard Tables of Food Composition in Japan. However, the beverages did not form large clusters and demonstrated scattered distribution on the map. Green tea, black tea, and coffee are located within or near the vegetable cluster whereas cocoa is near the pulse cluster. These results were ensured by the k-nearest neighbors. Thus, beverages made from natural materials can be categorized based on their origin. Visualization of food composition could enable an enhanced comprehensive understanding of the nutrients in foods, which could lead to novel aspects of nutrient-value-based food classifications. To maintain and promote public health, it is important to follow a healthy and balanced diet that has adequate nutrient levels. To encourage the adoption of balanced diets containing diverse foods, the World Health Organization (WHO) established a \u201cHealthy diet\u201d , and sevDetailed information on food composition is a prerequisite for implementing dietary guidelines . In JapaThe visualization of high-dimensional datasets, such as food-composition tables, increases awareness of the nutritional value of foods. Data-reduction techniques are useful for investigating high-dimensional datasets. Principal component analysis (PCA) is one of the techniques that havThis study aimed to classify foods based on nutrient information in the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition). We used the t-SNE mapping method and the k-nearest neighbors (k-NN), which lead to the estimation of appropriate nutrient intake through FBDGs. This nutrient value-based evaluation of food would enable a comprehensive understanding of the relationship between nutrients and food.The Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition) is an open source publication from the Ministry of Education, Culture, Sports, Science and Technology, Japan, in which 2478 foods were divided into 17 food groups. In this study, 16 food groups, except for \u201cPrepared foods\u201d, were used for analysis; \u201cPrepared foods\u201d was included in meal. The 16 food groups and number of foods in each group are shown in n-6 PUFA and n-3 PUFA, and 1\u20138% of foods for vitamins D, E, K, B6, B12 and C; folic acid, pantothenic acid; zinc, copper, and manganese. Therefore, the imputation method was applied to estimate missing values using multidimensional scaling (MDS), which represents measurements of similarity among pairs of objects as distances between points of a low-dimensional multidimensional space, and random forest regression methods based on four steps can be obtained based on the MDS. Here U has compressed information of X. Step 3: A regression model of jth variable of xj without missing values based on U was created by random forest. Step 4: Using the random forest regression models, missing values were calculated for jth variable. Steps 2 and 3 were performed for all variables X.Step 1: The distance between objects can be calculated using Equation (1).1, vitamin B2, niacin equivalent, vitamin B6, vitamin B12, folic acid, vitamin C, sodium, calcium, magnesium, iron, zinc, copper, iodine, selenium, and molybdenum. RDA is composed of proteins, vitamins A, B1, B2, niacin equivalents, B6, B12, folic acid, C, calcium, magnesium, iron, zinc, copper, iodine, selenium, and molybdenum. AI is composed of n-6 polyunsaturated fatty acids, n-3 polyunsaturated fatty acids, vitamin D, vitamin E, vitamin K, pantothenic acid, biotin, potassium, phosphorus, manganese, and chromium. DG is composed of proteins, fats, saturated fatty acids, carbohydrates, dietary fiber, sodium, and potassium. In this case, the selected nutrients were energy, water, protein, fat, saturated fatty acid, n-3 polyunsaturated fatty acid, n-6 polyunsaturated fatty acid, dietary fiber, carbohydrate, sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, copper, manganese, vitamin A , vitamin D, vitamin E , vitamin K, vitamin B1, vitamin B2, niacin equivalent, vitamin B6, vitamin B12, folic acid, pantothenic acid, and vitamin C, whereas iodine, selenium, chromium, molybdenum, and biotin were excluded.The accuracy of the missing values was validated by removing 50 known values and estimating the values for the imputation method as described in the Methods Section . The aveNutrient-density data were used for mapping to exclude the effect of water. Thus, the data for nutrients per 100 g of edible portion were converted to per 100 kcal. Water and energy data were excluded from the dataset during conversion. All nutrients were mapped. Furthermore, to evaluate the contribution of macronutrients to the mapping, we performed mapping using nutrients without them.A two-dimensional map of the nutrient matrix consisting of nutrients per 100 kcal and 2221 foods was constructed using t-distributed stochastic neighbor embedding (t-SNE). t-SNE is a nonlinear dimensionality reduction method in which Gaussian probability distributions over a high-dimensional space are constructed and used to optimize a Student\u2019s t-distribution in a low-dimensional space. The low-dimensional embedding descriptors, that is, nutrients per 100 kcal, can be obtained by minimizing the Kullback\u2013Leibler divergence between The k-NN, a type of machine-learning model ,21, was All data in the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition) were imputed. The numbers of foods consumed before and after data imputation are presented in 1, niacin equivalents, vitamin B12, and pantothenic acid were present in the first quadrant. Moreover, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, dietary fiber, sodium, potassium, calcium, magnesium, iron, copper, manganese, vitamins A, D, E, K, B2, B6, folic acid, and biotin were located in the fourth quadrant.Two-dimensional mapping was performed using/100 kcal data after data imputation. The results of mapping all nutrients using t-SNE are shown in The k-NN method was used for ensuring classification accuracy. The number of foods misclassified using k-NN is shown in n-6 polyunsaturated fatty acids, dietary fiber, manganese, and vitamin C are located in the first quadrant. Sodium is present in the second quadrant. n-3 polyunsaturated fatty acids, magnesium, phosphorus, iron, zinc, copper, vitamin D, vitamin B2, niacin equivalents, vitamin B6, vitamin B12, and pantothenic acid is located in the third quadrant. Saturated fatty acids, potassium, calcium, vitamins A, E, K, B1, and folic acid is located in the fourth quadrant.The results of the mapping with nutrients, excluding macronutrients , are shown in This is the first visualization study which was undertaken using t-SNE with the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition). Furthermore, this study showed that visualization by two-dimensional mapping was possible based on nutrient information in food-composition tables, as shown in a previous study . PreviouThe results showed that most foods formed clusters in accordance with the food groups in the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition), as indicated by the misclassification rate. This indicates that many food groups had common nutrient patterns and were categorized based on nutrient similarity. Furthermore, as shown in In contrast, the beverages did not form large clusters and were scattered. The misclassification rate of beverages was 48%, with the highest rate among the food groups. This may be because this food group comprises a wide range of beverages, including soft drinks, beverages made from natural materials , and alcoholic drinks. In There is no international consensus on the definition of vegetables and fruits; thus, definitions vary among countries or cultures . The StaThe Japanese Food Guide Spinning Top was developed by the Ministry of Health, Labour, and Welfare and the Ministry of Agriculture, Forestry, and Fisheries of Japan in 2005. A diet that adheres to the Japanese Food Guide Spinning Top decreases the risk of total mortality and mortality from cardiovascular disease . Figure This study has some limitations. First, information on iodine, selenium, chromium, molybdenum, and biotin was not added to the dataset for data imputation and mapping because the number of available foods was insufficient. Secondly, details of bioactive compounds, such as phytochemicals and peptides, and the quality of nutrients, such as amino acid balance and fatty acid composition, were not included in the dataset of this study. Finally, this study employed nutrient density and did not reflect the actual nutrient quantity of real intake in the mapping. When data from the Standard Tables of Food Composition in Japan increase and nutrient data become available, more precise mapping will be performed. Analysis of the quality of nutrients or other compounds may lead to a better understanding of food characteristics.In conclusion, this is the first report on t-SNE-based visualization of the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition), and the results showed that most foods formed clusters in accordance with the food groups in the Standard Tables of Food Composition in Japan, 2020 (Eighth Revised Edition) in terms of nutrient values. In contrast, beverages did not form a large cluster, and beverages made from natural materials such as green tea, black tea, coffee, or cocoa were categorized based on their origin. The visualization of food composition enables a comprehensive understanding of the nutrients in foods, thereby leading to novel aspects of food classifications based on nutrient values."} +{"text": "Instead of \u201cSchool of Clinical Medicine, Henan University, Kaifeng, China\u201d, it should be \u201cDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, China\u201d.In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Our results show that the points of convergence between the classifications were the classification in terms of origin , nutrient sources, and food groups. However, inconsistencies were observed for the distribution of food items in each group in the 98 surveyed FBDG. As for nature, there was a convergence for in natura, minimally processed, and processed foods. However, the criteria adopted for minimally processed and processed foods described in the FBDG differ from those considered by the FST. FST also does not recognize the classification of foods concerning the level of processing.The World Health Organization (WHO) proposed the dietary guidelines presented as the Food-based Dietary Guidelines (FBDG). The FBDG classify foods according to their origin, nature, nutrient source, food group, and processing level. Food science and technology (FST) ranks food according to its origin, perishability, nutrient source, processing, food group, and formulation. This paper aimed to compare the convergence points for food classification according to the FBDG and FST. This study was carried out in two phases. The first step was identifying the Food-Based Dietary Guidelines (FBDG). For each of the FBDG, food items were grouped as fruits, vegetables, cereals, sugars, fat and oils, legumes, foods from animals, dairy products, and others. The second step aimed to identify and describe the different food classification systems. The search was performed on PubMed Food consumption has been recognized as an essential predictor of health or behavior that strongly influences health and future disease risk. Food composition and classification data are used in health studies, from which results are the basis for formulating public policies ,3,4,5,6.Such divergences are probably observed because two fields of scientific knowledge, although closely related, assign different criteria to classify foods: the first referring to food production and the second related to food and its effects on health. Many sciences, such as physics, chemistry, mathematics, and biology, bypassed the scientific development of food science and technology ,14. At tThe Codex Alimentarius covers topics related to food production at all stages of the production chain. It includes processed, semi-processed, and in natura foods. It also addresses issues related to the production of conventional and specialty foods, labeling, food hygiene, food additives, pesticide residues, and food safety assessment procedures derived from modern biotechnology, food inspection, and certification ,16,17. The changes from the First and Second World Wars in the production and sale of food, resulting from the economic, political, and social context, also led the population to move from a situation of malnutrition prevalence to the current state, in which excess weight takes on epidemic proportions ,21,22,23In this sense, the proposals for organizing, creating classification systems, food description systems, or even categories for describing foods may have different objectives, contributing to generating other groups: to create databases on the composition of foods; to support research and technological development; to monitor international, national, and regional trade in food items; to study the relationship between food consumption and health; to monitor the use of pesticides, dyes, antibiotic residues, and veterinary drugs, among others ,27,28,29The classification of foods aims to group them according to their physical, chemical, nutritional, and biological characteristics, as well as other food components, seeking, among other interests, the creation of programs and policies in the area of nutrition, health, and in the fields of agriculture and food industry ,31,32,33Food classification systems aim to organize and distribute a set of elements according to an order established by legal documents, consumers, and food professionals ,10,14. SClassifying food in multiple dimensions is possible. However, it is essential that a food classification standard becomes a reference for the population and data obtained in epidemiological research in different regions of the world are comparable and equally interpreted, and understood by consumers, professionals, and scientists in the public health, nutrition and FST ,38,39. IIn this regard, in 1998, the World Health Organization (WHO) proposed dietary guidelines as Food-based Dietary Guidelines (FBDG). FBDG aim to guide the population regarding food consumption and recommend that meal planning is based on foods that provide a healthy and balanced diet. They incorporate the consumption characteristics of each country and their eating habits, providing recommendations for which foods to eat or not ,40,41,42The FBDG classify food items according to their origin, food groups, nature/processing, and nutrient sources and food science and technology (FST) classifies foods according to the degree of perishability, origin, nutrient source, nature, processing, and formulation ,45,46,47This study was carried out in two phases . The fir\u00ae, Science Direct, and Web of Science and websites of international organizations such as the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the Codex Alimentarius. The following combinations of descriptors were used to search: \u201cfood classification\u201d and \u201cfood classification systems.\u201d The search was performed on 10 August and 11 August 2022, without limitation on the date or origin of the studies. To locate possible studies not found in the initial search, the authors performed a reverse search using the reference lists of the selected articles. Inclusion criteria were original and review articles on (1) food classification systems, (2) food guides, (3) food processing, (4) food industry, (5) industrialized food, and (6) processed food. Exclusion criteria were randomized clinical trials, experimental studies, case studies, and studies that brought an association between a particular food group and/or dietary guidelines and diseases. A total of 66 articles and international documents (specific legislation) were included ; the life cycle ; origin (exotic and autochthonous); the way the product is presented to the consumer ; based on the edible parts . The botanical characteristic is the most appropriate for naming these food items in their groups because they are stable. For this purpose, three taxonomic units are used: the botanical family , the botanical genus (group of related species), and the botanical species (basic taxonomic unit), bringing together very similar plant characteristics ,75,76,77Phaseolus vulgaris), broad bean (Vicia faba), lentil (Lens culinaris), chickpea (Cicer arietinum), dry pea (Pisum sativum), and vigna (Vigna sp.) are considered \u201cpulses\u201d, and they are distinguished from leguminous oil seeds by their low-fat content [Cereals are vegetables that, botanically, belong to the grass family. Their seeds are harvested when dried and comprise species such as rice, wheat, corn, barley, triticale, rye, millet, sorghum, and oats ,80. Cere content ,81,82,83Oilseed consists of seeds from various plants that produce edible vegetable oils, seed meals, and cakes for animal feed. Some important vegetable oil seeds are by-products of fiber or fruit crops . Some of the oilseeds are, directly or after slight processing , used as food or for food flavoring ,59. Codex Alimentarius, meat is the matured muscle mass and the other tissues accompanying it, including the corresponding bone mass, offal, blood, fat, cartilage, and bones. Its classification is related to the species from which it precedes: beef, pork, lamb; poultry ; fish ; hunting ; reptiles; batrachians ; chelonians ; insects [According to insects ,84. In t insects ,86,87. M insects . Foods of animal and vegetable origin can be classified as perishable or semi-perishable since the water activity content in the food matrix affects the speed of deterioration, mainly of microbial origin. They can be classified as in natura, minimally processed, and processed according to their nature. Fresh food refers to food in its natural state . MinimalIn this context, foods are classified as pasteurized, dehydrated, evaporated, extruded, refrigerated, frozen, lyophilized, irradiated, fermented, and enriched, among others ,70,91,92Thus, the International Network of Food Data Systems (INFOODS) proposes the classification of foods based on their composition as simple foods and compound foods. Simple foods are those that have the following criteria: (a) foods in their natural state, only inedible or rejected parts are removed ; (b) foods from which part of the edible portion has been removed during processing ; (c) foods with a single main ingredient, dehydrated or with added water ; (d) foods with a single main ingredient, added with other ingredients in amounts that do not significantly impact the energy value; (e) foods that have been processed with or without the removal of parts of the edible portion, with or without the addition of small amounts of other ingredients, such as fortified corn flakes. Compound foods consist of raw materials with ingredients from different sources, such as cakes, bread, and ready-to-eat products, among others ,28,45,94n = 98) have FBDG to guide the consumption of necessary foods for health promotion. The regions with the highest number of FBDG are the European continent (n = 34), the American continent\u2014Latin America and Caribbean (n = 29), and the Asian continent\u2014Asia and Pacific (n = 17). Although Africa has 54 countries, only 10 have FBDG; Oceania has 6 countries with FBDG . Although 94 FBDG use classification according to food groups, we identified that some countries adopt combinations of food groups with nature and/or nutrient sources and/or origin, such as the FBDG of Peru, Israel, and Belgium, among others. Alternatives such as nutrient sources or according to their nature/processing , origin and culture of the country are the minority . The most usual systematization in the FBDG is food groups (n = 1); highly processed foods, rich in sugar and fat (n = 1); processed foods (n = 5); processed foods high in fat, sugar, and salt (n = 1); in natura or minimally processed (n = 3); ultra-processed foods (n = 4). Of these countries, Brazil, Ecuador, and Peru use the NOVA classification [In seven FBDG , foods are classified as highly processed foods (d foods) ,35,95. Bn = 57; 58%), vegetables , oils and fats , vegetables and fruits , and foods from animals .Two hundred thirty-five terms were cited to name the food items in the respective groups described in the 98 FBDG . The mosIt is important to mention that the \u201cdairy products\u201d group is separated from the \u201cFood from animals\u201d group because, although the name food from animals is the most used for foods of animal origin, not all food groups of animal origin include dairy products (there are 30 terms related to the specific nomenclature \u201cmilk or dairy products\u201d). Therefore, this separation was maintained in this manuscript.n = 8; 8% of the 98 FBDG), 13 for the vegetable group , 52 (53%) for the cereal group, and 11 (11.2%) terms were listed as foods belonging to the legumes group (n = 46) described fruits and vegetables in the same group; 20% (n = 20) included fruit juice; nine (10%) included beans; in eight (8%) FBDG, legumes were also part of this group. Forty-seven FBDGs included legumes in the protein sources group [We found 84 terms to specify food items in the fruits, vegetables, cereals, and legumes groups. In total, 8 terms categorized foods into the fruit group , chemical composition, and nutritional value. Only their origin, e.g., plant origin, is the common criterion.n = 64) were foods from animals or protein sources, such as meat, poultry, pork, game meat, offal, fish, seafood, meat products , insects, eggs, tofu, milk, yogurt, cheese, beans, soy, pulses, peanuts, seeds, and oilseeds/nuts included peanuts, and thirty-nine (40%) had soy in this group; 90% of the FBDGs incorporated eggs and fish into the group food from animals and only twenty FBDG (20%) included the seafood in that group. Likewise, we identified that some of the terms used to name the food items belonging to the legumes group in the analyzed 98 FBDG are related to foods belonging to other groups, such as nuts (fruit), soya (oilseed), and meat . Of the 235 identified terms, 27% of these of the terms named foods from the milk and dairy product group: milk, cheeses, yogurts, dairy products, tofu, curds, labneh, foods rich in calcium, kefir , soy milk , tofu (Cambodia and Yugoslavia), and eggs . Only one (1%) FBDG (Oman) added dry curd (labneh) to this group. Furthermore, of the 235 terms used to identify the food items of each group, only 9% terms were associated with oils and fats, e.g., butter, margarine, oils obtained from seeds, avocado, coconut, and olive oil. Fifteen FBDG (15.3%) included avocados in this group, while coconut was included in this group in ten (10.2%) of the FBDG . Twenty-two terms were used for food items in the sugar group. However, words like \u201chighly processed foods rich in sugar and fat; oil; butter; fat; rice\u201d are inconsistent with the proposed grouping . In the FBDG from Brazil, Ecuador, and Uruguay, foods were classified according to the NOVA (classification of foods based on the extent and purpose of their processing), which ranks foods as in natura/minimally processed (Group 1); in Group 2\u2014oils, fats, salt, and sugar (processed culinary ingredients), Group 3\u2014processed foods, and Group 4\u2014ultra-processed foods 3,12,24,114,115.The present study investigated convergence points between the classification of foods adopted by the researched Food-based Dietary Guidelines (FBDG) and the criteria adopted by food science and technology (FST). Our data show points of convergence when using criteria related to origin, nutrient sources, nature/processing, and food group . Our stun = 13; 13%) FBDG used terms associated with the classification according to nutrient sources.The current trend is for FBDG to be based on the dietary pattern of the target group, not nutrients . Based on = 1259) of these consumers believe it is easier to classify foods into food groups [The types of classification most adopted by the FBDG are those related to food groups and nutrient sources. However, most FBDG (94%) are classified according to food groups, a criterion also used by FST, rather than nutrient sources . A recenRegarding fruit and vegetable classification, approximately 49% of FBDG group fruits with vegetables. Fruits and vegetables, when correctly consumed in terms of frequency and quantity and combined with other foods, promote health benefits. Therefore, it is important to consider the analysis of the formulation, with the final nutritional composition of a product that uses fruits and vegetables as raw materials, as well as the addition of sugar, fat, and salt to these preparations ,116,117.Beans and other legumes are foods that are classified differently according to the different FBDG. They are included in the fruit and vegetable group, the cereals group, or even included in the food from animals group and with oilseeds. As we have already highlighted, these foods differ in chemical composition and nutritional properties. Legumes are known to be grains contained in pods; as they are grains, in 13% of the 98 FBDG, they are classified as cereals. However, legumes differ from cereals ,123,124.Twenty-three (23.5%) FBDG adopted a specific legume group, justified by their nutritional properties and anti-nutritional factors. These modify their recommendation compared to other foods, such as cereals, meats, and oilseeds ,122,124.Approximaely 40% of FBDG incorrectly included pulses, soy, and peanuts in the food from animals group. Both soy and peanuts are products of plant origin and do not have high biological value proteins. In addition, peanuts are legumes with a high fat content ,123,124.FBDGs of 17 Latin American countries added green bananas to the cereals and pulses group. In green bananas, 60\u201380% of the carbohydrates are fiber . Their ingestion is recommended since they behave in the body similarly to fibers and are considered healthy products ,129. Eggs, milk, and derivatives are products of animal origin with high nutritional quality recognized as important for human health. Their protein composition provides individuals the essential amino acids to develop and maintain vital activities ,124,126.The FBDG of Vietnam, Korea, Cambodia, and Kenya included in their dietary guidelines the consumption of insects in the protein-rich foods group, most likely due to the impact of the traditional intake of insects in these countries ,130,131.n= 15)) and 10 (10.2%) of the FBDG included avocado and coconut in this group, respectively. From the point of view of FST, avocado and coconut are fruits with high-fat content. It is known that oils , generally liquid at room temperature, have higher contents of monounsaturated and polyunsaturated fatty acids, except for coconut and palm oils. Olive oil is part of this group, but this term is only used to name oils from fruits: palm oil and olive oil. On the other hand, fats of animal origin, solid at room temperature, are the primary sources of saturated fatty acids such as bacon, lard, and dairy fat. Physiologically, they behave differently in the body; therefore, the fat type should be better specified in dietary recommendations [In the oils and fats group, almost 15 terms for the sugar group in the FBDG. Some authors consider \u201csugars\u201d all sugars used as ingredients in processed and prepared foods such as bread, cakes, soft drinks, jams, chocolates, and ice cream. Total sugars are mono and disaccharides naturally present in food, such as lactose in milk, sucrose in table sugar, or glucose and fructose in honey. Table sugar is a product obtained from sugar cane or sugar beet. Such substances are used to impart sweetness to food, among other technological properties, including preserving food ,135,136.Codex Alimentarius recommendations, while the logic for classifying foods in the FBDG does not harmonize, for example, origin, group, and main source of nutrients, as verified for foods of plant origin and legumes. Despite identifying divergencies concerning food classification, it is essential to mention that FBDGs are designed for another purpose than a food composition table or the classification carried out by FST. However, guiding the population using correct and understandable classification is crucial to avoid misinterpretation.Comparing the food groups described in the 98 FBDG, as well as the food items included in the groups, with the classification proposed by the FST, we identified that despite convergences regarding the sort, e.g., animal origin and vegetable origin, there is incompatibility regarding the inclusion of items in the groups . FST follows the The NOVA classification system groups foods as in natura or minimally processed, processed, and ultra-processed foods . AlthougConsidering the classification in terms of nature and food processing proposed by the FBDG and FST, we understand that they considered the same classification: in natura, minimally processed, and processed. However, the concepts proposed by FST differ from those established in the FBDG since minimally processed food, according to FST, is defined as any fresh fruit or vegetable or any combination that has been physically altered from its original form but remains fresh. The critical point of minimally processed fruits and vegetables is their active metabolism and respiratory rate despite physical changes ,70,89,90Furthermore, in the FBDGs of Brazil, Peru, Ecuador, and Uruguay, the term ultra-processed is used to classify some foods. According to the NOVA classification, ultra-processed foods are industrial formulations made entirely or mainly from substances extracted from food , derived from food constituents (hydrogenated fats and modified starch), or synthesized in the laboratory based on organic materials such as petroleum and coal ,114,137.Industrialized foods can be added sugars, lipids, sodium, or food additives that can harm health when added improperly or when consumed in excess ,70. SimiRegarding the presentation of information on the classification of foods in the FBDG, some authors have shown that information on whether foods are sources of calcium, fat, or proteins still needs to be fully understood by the population ,121,139.Advances in the labeling of industrialized products that identify, in addition to the product\u2019s name, the list of ingredients, the nutritional information, and property claims on labels, provide better understanding, often restricted to professionals ,147,148.According to Sadler et al. , preciseCodex Alimentarius signatory country follows its recommendations, including the nomenclature of foods of animal and plant origin, whether in natura, minimally processed, or processed [Thus, to reduce information asymmetry between researchers, public policymakers, and consumers, using terms that nutritionally reflect food items for daily consumption is recommended, considering reliable data on their chemical composition that expresses the nutrition composition and sources of nutrients . Public rocessed ,149. Humrocessed ,150,151.In the modern world, convenience is needed, and the food industry is essential. After approximately 200 years of the food industry\u2019s existence and 60 years after food engineering became an established field of science, this has not been enough for some people to trust and feel safe with industrialized food. Furthermore, people lack knowledge about industrialized food, quality, and food safety, so how can they trust in something they do not know sufficiently? Including food subjects in basic education, such as food education, food safety, nourishment, good domestic food handling, and sustainability issues, must be considered in a public policy tool .Despite the various proposals developed in epidemiological studies, Deharveng et al. and IrelIn addition to classifying foods, it is important to evaluate the chemical and nutritional composition of foods, simple and compound, since recipes, technical preparation files, and formulations are made up of a group of instructions related to the quantity and quality of raw materials and ingredients, to the precise recording of all ingredients, their proportions, and sequence of operations. Systematized recipes, technical preparation files, and formulations reveal foods\u2019 chemical and nutritional composition and show trends in the relationship between food and nutrition ,36. The Our results showed that the classification of foods indicated in the 98 surveyed Food-based Dietary Guidelines (FBDG) established convergence with food science and technology (FST) for the criteria source of nutrients and origin of foods, animal or plant. By classifying foods in food groups in the FBDG, we identified that the distribution of some food items in food groups needs to follow the botanical classification recommended by FST for foods of plant origin. A similar approach can be considered for foods of animal origin. Legumes do not have the same nutritional value as animal foods. Presumably, such items were incorporated into the group because they were protein-rich. Using such groupings can lead to erroneous interpretations regarding the chemical and nutritional aspects in the interpretation of food consumption versus nutritional quality. Regarding the nature of foods, whether in natura, minimally processed, or processed, from a scientific and technological point of view, it is impossible to classify foods according to the \u201clevel of processing\u201d. Unit operations do not define the nutritional value of the food.A proposal for food classification should include eating habits, availability of products in the region, access issues (food security), technological development, and availability of data on chemical composition. We must consider and improve the consumers\u2019 food literacy, informing them that foods, regardless of origin and technical process, are sources of nutrients. Indeed, its chemical composition determines whether a food item is a source of a particular nutrient. The chemical composition of a recipe or formulation will decide if the product is high in calories and is a source of lipids or fibers. The issue goes beyond a list that groups foods and is directly related to the correct information interpretation from the aspect of FST. The result of the recipe adopted at home, in food service, or in industry determines the processed food\u2019s content, quality, and nutritional value. The results of this review reinforce an urgent need for shared work between professional nutritionists, food scientists and technologists, public policymakers, and representatives of the food industry to discuss the classification of foods. Just grouping foods into categories does not translate the nutritional value of a food or a product exactly. There is a need to further educate health workers and researchers regarding food classification; thus, they may not contribute to misinformation."} +{"text": "Author Contributions statement was not updated to accurately reflect the contributions of the newly added authors PP, GA, JG-A and ME. The correct Author Contributions statement appears below.Due to a production error, the in silico, in vitro and in vivo studies. BA, PP, GA, JG-A, ME, JL and PS analyzed data and contributed to their interpretation. JL and PS supervised the project. ME, JG-A, JL and PS received funding. All authors reviewed the manuscript, approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u201d\u201cBA, JL and PS conceived and designed experiments. BA, MR, NC, LS, JE, PP, GA and JG-A performed the The publisher apologizes for this mistake. The original article has been updated."} +{"text": "Author list, and Author \u201cJiayin Yang\u201d was erroneously excluded. The corrected Author list appears below.In the published article, there was an error in the \u201cYong Lv, Xiaolong Xie, Lihui Pu, Qi Wang, Jiayin Yang, Siyu Pu, Chengbo Ai, Yi Liu, Jing Chen, Bo Xiang.\u201dAffiliations. A new affiliation was added for \u201cJiayin Yang\u201d: \u201cLiver Transplant Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.\u201dIn the published article, there was an error regarding the Author Contributions as the contributions of Jiayin Yang were erroneously excluded. The correct Author Contributions appear below:In the published article, there was an error in the \u201cBX: study concept, and management and coordination responsibility for the research activity planning. JC: study concept, experiment design, data analysis, and critical revision of the manuscript for important intellectual concept. JY: sample acquisition, analysis and interpretation of data for the work, drafting the work and revising it critically for important intellectual content. YLv: study concept, data analysis and drafting of the manuscript, and implementation of the computer code and supporting algorithms. XX: sample collection, conducting a research and investigation process, data analysis, and drafting of the manuscript. LP: performing the experiments and data collection. QW: sample collection, scrub data, and maintain research data. SP and CA: sample and data collection. YLi: critical advice on study design and found support for this project. All authors contributed to the article and approved the submitted version.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cTui-Na department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China\u201d, it should be \u201cTui-Na Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Consumers are more aware and demanding of healthy food options, besides being concerned with environment-friendly consumption. This paper aims to evaluate nutritional, technological, and sensory characteristics of legumes and their products\u2019 quality and versatility, considering potential applications in new food options. Legumes are foods that have a recognized nutritional group since they have high protein and fiber content. However, their consumption is still somehow limited for some reasons: in some countries it is not easy to find all the species or cultivars, they need an organization and planning before preparation since they need soaking, and there is the presence of antinutritional factors. Due to the different functionalities of legume proteins, they can be applied to a variety of foods and for different purposes, as grains themselves, aquafaba, extracts, flours, brans, and textured proteins and sprouts. These products have been inserted as ingredients in infant food formulations, gluten-free foods, vegetarian diets, and in hybrid products to reduce food costs as well. Foods such as bread, cakes, cookies, meat analogues, and other baked or cooked products have been elaborated with nutritional, technological and sensory quality. Further development of formulations focused on improving the quality of legume-based products is necessary because of their potential and protein quality. There is a wide variety of legumes: beans, soybeans, peas, lentils, chickpeas, lupins, carobs, and peanuts, which can be purchased green, dehydrated, in pods, sprouted, or in canned form .Pisum sativum L.) originating in the Mediterranean, especially in the Middle East, is one of the oldest domesticated crops in the world [Glycine max) has Asian origins and is one of the most versatile and nutritionally important legumes in the world [Cicer arietinum L.) is another legume with an important role in world food and is one of the most cultivated [Lens culinaris) is also a legume and it is estimated that in the year 2020 more than 6 million tons of lentils were produced in the world. Among the world\u2019s largest producers, Canada and India can be mentioned, and much of this production is exported [Pea , and Capes Portal, between February of 2020 and December of 2022.The identification of the studies was performed, and the papers were selected considering the following keywords: \u201clegumes\u201d; \u201cpulses\u201d; \u201clegumes flours\u201d; \u201cpulses flours\u201d; \u201clegumes proteins\u201d; \u201cprotein functionality\u201d; \u201ctechnological properties\u201d; \u201cnutritional and technological properties\u201d; \u201ctexture-modified foods\u201d; \u201csensory quality\u201d; \u201csensory properties\u201d; \u201clegumes plant-based\u201d; \u201clegumes products\u201d; \u201cnew food options\u201d.All the titles and abstracts of the articles were read in order to confirm if they addressed the study theme, and those that met all the inclusion criteria were read in their entirety. The targeted data included authors, legumes, food made, and outcomes. The inclusion criteria were (1) being compatible with the main subject; (2) free, online, digital access available for full reading and download. The exclusion criteria were (1) not being compatible with the main subject; (2) not addressing the topic of interest; (3) being an animal study; (4) being a dissertation, book, thesis, or literature review.Legumes consist mainly of carbohydrates 15\u201368%), proteins (15\u201340%), and dietary fiber (15\u201335%) and, depending on the legume, a varied content of lipids, especially soybean and chickpea. Cellulose is considered an important fiber component, found mainly in beans, peas, lentils, and green beans \u201368%, pro. These lIn legumes, the high amounts of protein deserve to be highlighted, which can vary from 20% in peas to 38\u201340% in soybeans and lupines . Legume The digestibility of legumes is lower than that of cereal proteins and this inferiority can be attributed to several factors that are related to the protein\u2019s structure and functionality, such as relative solubility, compartmentalization, bean proteins structure compactness, cell walls permeability, and seed protective coating, in addition to the presence of substances in the seed coat, such as tannins and phytic acid, which can form insoluble complexes with amino acids, making them unavailable for absorption ,26. ThisDespite having nutritional, sensory, and versatility advantages in cooking , legumesLentil-based foods have been successfully produced and marketed in recent years. Lentils are known to induce severe allergic reactions; however, it is currently unknown whether new lentil-based pasta retains the same allergenic potential as lentil seeds. Valdelvira et al. studied With regard to bioactive compounds, legumes have several types of compounds depending on the variety of species, color, and type of processing of the legume. For example, lupine seeds contain low amounts of carotenoids and high concentrations of tocopherols and phenolics. However, the chemical composition of Andean lupine flour was modified by the technological processes applied ,33. AfteGermination, also known as sprouting, is the process of soaking the legumes in water and keeping them in moist conditions until they begin to germinate . LegumesB-complex vitamins, for example, can increase in germinated grains, such as lentil sprouts, of which some studies already found a significantly higher amount than in dry lentil seeds . The gerChickpea germination for 72 h followed by boiling, drying, and peeling was considered a useful technique for cooking or as a thickener for follow-on infant formulas fortified with minerals and vitamins . OhanenyBresciani and Marti evaluatePerri et al. germinatAhure and Ejoha evaluateLegume flours have been inserted in diets with or without gluten to make breads , cookiesThe addition of legume flour also favors viscosity, dough volume, specific bread volume, cake tenderness, and texture of bakery . Legume Giuberti et al. made spaHoehnel et al. evaluateKomeroski et al. evaluatePasqualone et al. studied Joehnke et al. studied Du et al. studied Evangelho et al. studied Ma et al. evaluateRecent studies have shown that the viscous liquids that can be drained from cooked or canned legumes produce stable foams, emulsions, and gels. This liquid, called aquafaba, can be used as a gluten-free and cholesterol-free vegan rheological additive in many food products such as egg-free mayonnaise, meringue, mousse, whipped cream, ice cream, emulsified sauces, cocktails, and confectionery products. A recent study with chickpeas, beans, lentils, soybeans, and peas investigated the use of such ingredients ,63.Chickpea in aquafaba was studied by Mustafa et al. . AquafabStantiall et al. also evaShim et al. evaluateAquafaba\u2019s physical properties, such as pH, density, viscosity, water, and oil absorption capacity, determine the functional properties of this new product. The lower pH of aquafaba can lead to an increase in foaming and emulsification properties ,63,66.Many consumers are concerned about aquafaba\u2019s oligosaccharides, as such compounds can cause unpleasant gastrointestinal symptoms such as flatulence, bloating, diarrhea, and abdominal pain . HoweverDue to its functionality, aquafaba can be used in food products, such as vegan mayonnaise and butter , and gluThe perspectives for consumption and marketing of legumes as substitutes for animal source foods also seem very promising due to the quality of the proteins in such grains, and the motivations are quite varied: for vegetarians, for nonvegetarians who respect animals, people who want to consume foods without cholesterol, or for religious or ethical reasons.Ma et al. evaluateConsumers can have more than one motivation to replace meat with legumes and as an ingredient in processed foods, because of their promising processing qualities, since legumes can be included in many convenient products. In addition, the increased consumption of processed legumes products could reduce the use of meat in many dishes .Meat substitutes deserve to be further evaluated, especially regarding technological quality and acceptance, as some people who are interested in their consumption require that they be practical and have sensory characteristics close to the usual meat products such as appearance, texture, and general acceptability . Kim et Legumes can also be used for special diets like for people with dysphagia . The maiProtein aggregates result in thickening, increased viscosity, and the formation of a gel, whereas interactions between the denatured protein and the gelatinized starch of the legume grain contribute to the increase in apparent viscosity . ChickpeFood made with legumes as ingredients can profit from the quality of the proteins of these grains, since they may have functional properties such as solubility, water and oil retention capacities, gelling, emulsification, and foaming, among others, which are known to improve food texture ,77,78.Several minimal nonthermal processing methods are being used to induce significant changes in protein conformation and modulation without altering its native characteristics. Pulsed light, high-pressure processing (HPP), irradiation, ultrasound, supercritical carbon dioxide, plasma technology, and pulsed electric field (PEF) are emerging technologies. HPP treatment induces denaturation and aggregation or gelling of proteins with high textural properties. The functional properties of legume proteins such as hydration, gelling, and emulsification make legume proteins also suitable for industrial applications .Viscosity, water and oil retention capacity, and activity and stability of emulsions in legume preparations are influenced by the content of protein and soluble/insoluble carbohydrate ,80, polyWater absorption during immersion followed by high-temperature treatment during cooking leads to hydration and protein denaturation and starch gelatinization, in addition to solubilization ,81. ChanSoy protein has been widely used in the food industry for such purposes, in addition to peas, lentils, beans, and chickpeas ,84. In aAccording to their diverse functionalities and nutritional properties, legume proteins can be applied in a variety of foods and formulations and for different purposes. These functional properties make it possible to use legume proteins in the form of extracts, flours, textured proteins, and other derivatives in preparations such as soups, beverages, snacks, baked goods, or meat analogues . Some imThe secondary structure of legume proteins is directly linked to the functional characteristics and changes that occur in protein conformation, for example, emulsifying and foaming properties of legume proteins. High-pressure processing exposes the larger sites, which significantly improves protein digestibility due to structural loosening and protein unfolding .Different processing conditions can affect protein properties and functionality. In general, heat treatments such as cooking, microwave cooking, pressure cooking, and extrusion increase the digestibility of in vitro protein. In addition, an increase in cooking time was shown to be important for increasing in vitro protein digestibility (IVPD). Cooking resulted in better IVPD for lentils, chickpeas, peas, and soybeans, but soaking legumes before heating did not result in consistent effects. In microwave cooking, the lowest amount of energy (500 J/g) caused a significant increase in protein digestibility. A further increase in energy to 1000 J/g significantly improved protein digestibility. However, more energy input during microwave cooking did not significantly affect protein digestibility. Soaking before pressure cooking reduced processing time and positively affected bean protein digestibility, as IVPD improved. With regard to the baking process, apparently, the process of mixing, kneading, rising, and baking the dough reduced IVPD in relation to cooking, except for the red lentil. The extrusion of common bean, pea seed, broad bean, and kidney bean flour significantly increased the IVPD up to 87% [Legumes have nutritional, technological, and sensory potential to be added to foods and become new options, and their low environmental impact should also be highlighted. However, some factors limit their use, in addition to the presence of antinutrients, which can be minimized through planning, hydration, and heat treatment. Germinated legumes have been used to improve the nutritional and sensory profile of preparations in addition to presenting lower levels of antinutritional factors.Due to the different functionalities of legume proteins, they can be applied to a variety of foods and formulations and for different purposes, whether in the form of the grains themselves, aquafaba, extracts, flours, brans, and textured proteins. From a technological point of view, the incorporation of legumes in cereal-based products has been welcome, whether for celiac individuals or people sensitive to gluten, as a strategy that adds nutritional value and expands food options. However, dough rheology and the technological quality of breads, cakes, and biscuits still need to be further investigated.Many people benefit from this increase in the consumption of legumes, such as people who do not consume gluten, vegans, vegetarians, allergic and dysphagic individuals, in addition to the world population that already has the habit of consuming such grains, which have culinary versatility. It is considered financially accessible and more sustainable than the consumption of animal source foods.For future perspectives, our research group is focusing on evaluating the behavior of different legumes associated with other vegetable options in meat analogues, as well as chemical, technological, and sensory quality of these final products."} +{"text": "Dr. Hamidah Hussain.Dr. Hamidah Hussain embodied everything that a global health researcher, advocate, and leader should be. Her work improved and saved countless lives across Pakistan, Bangladesh, Tajikistan, Indonesia, South Africa, and the Philippines. She was the co-founding Director of IRD Global in Singapore, and the founding Country Director for IRD Bangladesh. Her work included active case finding for susceptible and drug-resistant tuberculosis (TB), childhood TB, TB preventive services, vaccine-preventable diseases, and malaria control programs. Hamidah previously worked at the Johns Hopkins Bloomberg School of Public Health in Baltimore, BRAC in Dhaka, and Aga Khan University in Karachi. She received her medical degree from Aga Khan University, her Master\u2019s in Health Policy, Planning, and Financing from the London School of Hygiene and Tropical Medicine, and her PhD in health economics from the University of Bergen. She is survived by her husband, Shehzad Noorani, their son Hisbaan, her parents, and a brother. She was still raising funds while in hospital for the public health programs that she was passionate about. Hamidah\u2019s extraordinary courage, graciousness, wisdom, generosity, and commitment to the underserved were widely admired. She was a bright star dimmed far too soon, a dedicated force when it came to saving lives. Hamidah will be greatly missed for her contagious smile and contributions to global health. A tribute to her beautiful life can be viewed here (tinyurl.com/tributetohamidah)."} +{"text": "Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide. This study guides the prevention and diagnosis of NAFLD by analyzing its risk factors and the diagnostic value of each index for NAFLD.We collected the clinical information of adults individuals who underwent physical examination in the Physical Examination Center of Qingpu Branch of Zhongshan Hospital, Fudan University, from January 2016 to January 2020, including gender, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). We performed logistic regression analysis and ROC diagnostic analysis.p-values were less than 0.05). Among them, age, BMI, ALT, TG, and HDL had a predictive value for the occurrence of NAFLD in the adults . The combination of age, BMI, ALT, TG, and HDL had a diagnostic value for the occurrence of NAFLD (AUC\u2009=\u20090.881).The results showed that age, BMI, SBP, ALT, AST, FBG, TBIL, TG, and LDL were risk factors for NAFLD in adults, and HDL was a protective factor (all Healthy people should pay attention to their BMI levels, manage blood pressure, blood glucose, and lipid levels, and pay attention to changes in ALT and AST index levels to prevent NAFLD. Age, BMI, ALT, TG, and HDL indexes are helpful factors in the diagnosis of NAFLD. The prevalence of NAFLD is estimated to be about 25% .NAFLD is a progressive disease characterized by the accumulation of early liver fat (hepatic steatosis) and liver inflammation, promoting the transition from benign steatosis to more advanced NASH. Although the disease is reversible in its early stages, its treatment becomes more complex in the advanced stages. If left untreated, NASH may progress to cirrhosis, an irreversible disease state characterized by scarring of the liver tissue that may lead to HCC . The maiGiven that the majority of patients with NAFLD are predominantly asymptomatic, early diagnosis of NASH and accurate staging of fibrosis risk are critical for better stratification, monitoring, and targeted management of at-risk patients. To date, liver biopsy remains the gold standard for the diagnosis of NASH and NAFLD staging. However, its use is not widespread due to its invasive properties. In this study, we analyzed the general information, biochemical indexes, and risk factors associated with NAFLD and searched for significant, relevant diagnostic indexes from physical examination data from a population in Qingpu, Shanghai.2.2.1.The study subjects underwent physical examination in the Physical Examination Center of Qingpu Branch of Zhongshan Hospital, Fudan University from January 2016 to January 2020. We collected their physical examination data. The inclusion criteria were patients diagnosed with fatty liver by B-ultrasound results, those with complete physical examination information, and patients aged \u2265 18\u2009years. The exclusion criteria are viral hepatitis, drug-induced hepatitis, autoimmune liver disease, Wilson disease (hepatolenticular degeneration), liver cirrhosis, liver cancer, severe malnutrition, infection, bile duct infection, severe cardiovascular and cerebrovascular diseases, other metabolic or immune diseases, cachexia and other malignant tumors, and long-term alcohol intake exceeding the standard . Duplicate samples were deleted.The patients were divided into a NAFLD group and a non-NAFLD (NO-NAFLD) group according to the criteria. Age, BMI, SBP, DBP, ALT, AST, TBIL, DBIL, IBIL, FBG, TC, TG, HDL, and LDL indexes were collected for comparison between the two groups. The diagnosis of fatty liver is based on the 2010 criteria of the Chinese Medical Association Society of Liver Diseases . Fatty l2.2.2 test. Data for skewed distributions were expressed as medians and quartiles and compared using the Mann\u2013Whitney U test. When the results of the descriptive analysis were statistically different, the factor was regressed by binary logistic regression. p\u2009<\u20090.05 was considered a statistically significant difference.Data were statistically analyzed using IBM SPSS 26.0 software, and R software (version 3.6.3) was employed to visualize and graph the results of independent factors. Descriptive information was expressed as .A total of 31,718 physical examiners\u2019 data were collected according to the above criteria, including 15,628 males and 16,090 females. In the 31,718-person sample, there were 16,968 patients with NAFLD and 14,750 people without NAFLD. There were differences in age, SBP, DBP, BMI, ALT, AST, TBIL, IBIL, FBG, TC, TG, HDL, and LDL between the NAFLD group and NO-NAFLD group with a cut-off value of 125.50. The prediction of BMI was accurate with a cut-off value of 23.25. The prediction of ALT was accurate with a cut-off value of 16.50. The prediction of TG was accurate with a cut-off value of 1.385. HDL was predicted with accuracy with a cut-off value of 1.315. The accuracy of the predictive ability of the remaining indicators was poor ; Table 34.In this study, we analyzed the health data of 31,718 patients to study the risk factors associated with the occurrence of NAFLD. We found that age, SBP, DBP, BMI, ALT, TBIL, FBG, TG, and LDL were risk factors for the occurrence of NAFLD and age, BMI, ALT, TG, and HDL were valuable for diagnosing NAFLD. We also performed a combined analysis of several indicators with an AUC area above 0.7 and found that the combined five indicators of age, BMI, ALT, TG, and HDL had diagnostic value for the diagnosis of NAFLD (AUC\u2009=\u20090.881).Here we found age a risk factor for NAFLD development. The results of multifactorial logistic regression analysis showed that the risk of NAFLD increased by 2.9% for each year of age, which is consistent with the results of several studies \u201311. The ALT is a common indicator of liver function. According to our study, ALT was an independent risk factor for the development of NAFLD , which is consistent with several other studies , 17, andOur study also identified SBP, DBP, BMI, FBG, TG, and LDL as risk factors for the development of NAFLD. Abnormalities in these indicators corresponded to each of the components included in METS. METS usually includes obesity, hyperglycemia, dyslipidemia, and hypertension . Some stObesity is a key factor in the development of NAFLD. In the present study, we found that BMI was a risk factor and the best predictor (AUC\u2009=\u20090.836) of NAFLD, which is in accordance with several other studies , 25. RecDyslipidemia is also a risk factor for the development of NAFLD. In this study, LDL was the strongest risk factor for NAFLD. The risk of NAFLD increased 1.285 times for each unit increase in LDL level. TG has diagnostic value for NAFLD by a ROC analysis study (AUC\u2009=\u20090.78). The pathogenesis of NAFLD is thought to be related to hepatocellular fat accumulation and dysregulation of fatty acid metabolism, leading to steatosis, as well as hepatocyte inflammation and necrosis , Shanghai Health Care Commission (202040065), Research Project of Qingpu Branch of Zhongshan Hospital, Fudan University (QYM2020-06), the Scientific Research Foundation provided by Pudong Hospital affiliated to Fudan University , Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP7202105), and the Pudong New Area Clinical Characteristic Discipline Project (grant no. PWYts2021-11).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Dear Editor,We read the article by Sun et al. published in Critical Care with great interest . The autAs is well known, antibiotics, especially broad-spectrum antibiotics, can cause significant disruption to the gut microbiota, including a 10,000-fold decrease in bacterial load and a decrease in diversity , 3. DiffFurthermore, there are also flaws in the analysis methods used in this study. Firstly, the authors used outdated OTUs for gut microbiota analysis, and ASV analysis was not performed, which weakened the power of this study. Secondly, the authors only used Lefse for differential analysis of gut microbiota between the two groups, without using more robust methods such as DESeq2. Thirdly, in this study, only a small proportion of the analysis results were adjusted for p-values, which can lead to many false positive results.Overall, this study has value of publication, but many issues still need to be addressed."} +{"text": "When chronic and intense, loneliness, in turn, may lead to distortions of sharing. For example, in less fortunate cases, the motivational force of loneliness is not so strong as to facilitate the sharing of our loneliness story with others or, even more, the sharing of the illusion of sharing (Kugiumutzakis, Third, I suggest that meaning. Acts of meaning (Bruner, emotional narratives with the Other (starting early in infancy; Stern, Fourth, because of the distortions of sharing, we cannot co-create Bruner, are impecultural membership, that is, finding one's place in the world as a doer and knower (Trevarthen, collective story-telling, which can be called \u2018socionoesis\u201d' (Trevarthen, symbolic and collaborative awareness (Trevarthen et al., cultural learning is facilitated and pride in meaning (Trevarthen, Finally, apart from the presence of an actual Other, synrhythmia, sharing and co-construction of meaning, it is The author confirms being the sole contributor of this work and has approved it for publication."} +{"text": "In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region.Race) on gestational weeks at birth using linear regression and on gestational age at birth categories using multinomial logistic regression.We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation , and some college relative to a master\u2019s degree or higher. Those with a high school diploma or less also had an increased odds of preterm and early term birth . In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category.After adjustment for NDI and ICERace.In this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICE It is wGestational age at birth is also an important determinant of cognitive and educational outcomes. Systematic reviews demonstrate that, relative to their full term peers, children born preterm are at increased risk for academic difficulties in reading and math and thosWithin the United States, there are stark disparities in gestational age at birth, including by maternal race and ethnicity , 13. FroRacial, ethnic, and geographic disparities in gestational age at birth are theorized to be related, in part, to differences in individual-level socioeconomic status (SES) . Those ode facto) via historical and contemporary systemic racism launched the ECHO program to investigate the influence of early life environmental exposures on child health and development. ECHO supports pediatric cohorts throughout the United States in the sharing of extant data and the collection of new data under a common protocol. This nationwide consortium is able to leverage demographic and geographic heterogeneity and a large sample size to answer important research questions about child health and development , 46. The2.2n\u2009=\u20098 cohorts were dropped). The secondary study population excluded three cohorts (n\u2009=\u2009547) that enrolled only preterm births (< 37\u2009weeks) and included 9,757 participants from 31 ECHO cohorts. This secondary study population was utilized to investigate the association between the exposures and gestational age outcome categories.The primary study population consisted of 10,304 participants from 34 ECHO cohorts who delivered a liveborn, singleton infant from 2000 through 2019 and who had the following outcome and exposure information available for analysis: gestational age at birth, maternal prenatal level of education, maternal race and ethnicity, and at least one geocoded residential address during pregnancy . We rest2.3in vitro fertilization or on artificial insemination (0%), obstetrical estimate from first trimester ultrasound (2%), obstetrical estimate from ultrasound taken in the second trimester with fetal biparietal diameter dating within 2\u2009weeks of sure last menstrual period (LMP) (0%), ultrasound taken in the second trimester with unsure or no LMP date (0%), report from obstetrical medical record reporting \u201cconsensus\u201d estimated date of delivery with no ultrasound documented during first and second trimester (8%), obstetrical estimate from LMP only (8%), neonatal estimate of gestational age at birth obtained from child medical records (39%), estimate from cohort research encounter (3%), report by mother (27%), and cohort-provided estimated date of delivery without further description (12%) , 48.continuous measure and a categorical measure . These categorizations were based on the definitions of the American College of Obstetricians and Gynecologists Committee Opinion that addresses match to and the algorithms and code that attempt to select the most accurate latitude/longitude location for each address . To asseRace) and the Race) , 55. We Race) , and preRace) , includiRace) . We chosortality . We calcortality , 57.NDI is a summary measure created through principal components analysis using the following eight census tract measures (as percentages): males in management and professional occupations, crowded housing, households in poverty, female-headed households with dependents, households on public assistance, households earning\u2009<\u2009$30,000 per year, adults with less than a high school education, and unemployed individuals . The cenRace was utilized to quantify the extent of racial segregation within the census tract and was calculated using the established formula in the census tract.TRace ranges from \u22121 to 1; a value of 1 signifies that 100% of the population of the census tract is concentrated in the most racially privileged group, whereas a value of \u22121 signifies that 100% of the population of the census tract is concentrated in the least racially privileged group. The census tracts were matched to their corresponding ICERace value and categorized into quartiles, with the first quartile (lowest proportion of non-Hispanic White persons) representing those least racially privileged.For this analysis, the most racially privileged category was defined as non-Hispanic White persons and the least racially privileged category was defined as non-Hispanic Black persons. ICE2.6via self-report and then categorized as non-Hispanic White, non-Hispanic Black, non-Hispanic Other Race, and Hispanic. Non-Hispanic Other Race included non-Hispanic persons who identified their race as American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, Asian, multiple races, or other race; these were collapsed into a single category due to small sample size.Maternal race and ethnicity were ascertained 2.7Geographic region was assigned according to United States Census regions categori2.8Covariates for inclusion in statistical modeling were selected based on their association with SES and gestational age at birth in the literature , 56, 58 Maternal age in years (continuous), child sex , and parity were based on medical record abstraction or maternal report. Prenatal marital status was based on maternal report and was categorized as married or living with a partner; widowed, separated, or divorced; or single, never married, and partnered not living together.via self-report or medical record abstraction with documentation of high blood pressure or anti-hypertensive medication use during pregnancy.Pre-pregnancy body mass index (BMI) was defined using measured or self-reported height and weight between 12\u2009months prior to conception through the first trimester and was categorized as underweight, healthy weight, overweight or obese according to accepted definitions . GestatiPrenatal substance use was ascertained through self-report or medical record abstraction for substance use during pregnancy. Binary variables (yes/no) for tobacco, alcohol, and marijuana use during pregnancy were created. Nicotine exposure was defined as cigarette smoking, use of Electronic Nicotine Delivery Devices/ENDS , and other forms of tobacco . Alcohol use included the consumption of beer, wine, mixed drinks, spirits, shot liquor, or any other type of alcohol.2.9Race according to maternal race and ethnicity categories and United States Census regions for continuous variables and the number of observations, missingness, and the percentage of total observations for categorical variables . Additio regions , 3. To e regions . We emplFor both linear and multinomial logistic regression modeling, we evaluated each SES measure of interest using an unadjusted model (without adjustment for covariates), a co-adjusted model (adjusting the estimate for each SES exposure for the other SES exposures), and an adjusted model .Additionally, we conducted two types of sensitivity analyzes. In the first sensitivity analyzes, we explored the effect of further adjusting linear mixed effect models for maternal health conditions and behaviors previously associated with SES and gestational age at birth, including pre-pregnancy BMI and pregnancy-related conditions and prenatal substance use , which could potentially confound or be on the causal pathway for any observed SES-gestational age at birth associations. In a second set of sensitivity analyzes, we performed \u2018leave one out\u2019 analysis in which we examined the point estimate for each SES measure of interest on completed gestational weeks in linear mixed effect modeling after excluding one cohort at a time.a priori hypotheses that there would be substantial variation by maternal race and ethnicity and United States Census region, adjusted linear models were stratified by maternal race/ethnicity categories and by United States Census region to examine differences by strata.We compared measures of association for unadjusted, co-adjusted, and further adjusted models to explore whether individual- and neighborhood-level measures of SES attenuate or potentiate observed associations by maternal health conditions and health behaviors. Based on Race; urbanicity; and Census region, with cohort membership as a classification variable. All statistical models were performed using non-imputed and imputed data. No substantial differences in estimated measures of association were observed when considering models based on non-imputed values and multiple imputation values; thus, we chose to present models based on imputed data since parameter estimates were more stable. Estimates of association by chained equations using the fully conditional specification with a discriminant function . Imputatociation \u20137 combinmice package . The package was usedgression , and the package was used33.1Race values were lower among mothers with lower educational levels relative to those with higher educational levels (bachelor\u2019s or master\u2019s degree). Substantial proportions of the study population resided in the Northeast (41.2%) and West (28.0%) United States regions, with smaller proportions from the Midwest (15.9%) and South (14.9%). Overall, 18.4% of participants were Hispanic of any race; 54.5% were non-Hispanic White; 17.3% were non-Hispanic Black; and 9.9% were non-Hispanic Other Race. Participants\u2019 mean age at birth was 30.5\u2009years (SD 5.6) and approximately 35% had not given birth prior to the index delivery. Just over 40% of participants had a healthy BMI (18.5 to less than 25.0\u2009kg/m2), with considerable variability by level of education .The primary sample consisted of 10,304 ECHO participants from 34 ECHO cohorts who delivered a liveborn infant from 2000 through 2019 with available participants\u2019 residential address during the prenatal period . The disRace varied by maternal race and ethnicity and after including age, marital/cohabitation status, parity, and child sex. In the unadjusted model, a significantly lower gestational age at birth was observed among those with higher levels of neighborhood deprivation (third and fourth quartiles) relative to the first quartile (lowest deprivation), with attenuation of the effect with co-adjustment for the other SES exposure variables and virtually no change in the effect estimate with further adjustment for age, marital/cohabitation status, parity, and child sex. When considering the principal exposure of ICERace quartile, in the unadjusted model, a significantly lower gestational age at birth was found among those residing in census tracts in the first quartile relative to the fourth quartile ; with co-adjustment and in the adjusted model, no significant associations were observed between ICERace and gestational age at birth.Gestational age at birth was significantly lower among those with up to a high school diploma or less and some college relative to those with a master\u2019s degree or higher across all models , with minimal change in the effect estimate after adjusting for the other principal exposure variables were associated with gestational age at birth outcomes for the secondary sample in unadjusted, co-adjusted, and adjusted models . These r3.3.1In the unadjusted model utilizing the secondary study population, having a high school diploma or less vs. a master\u2019s degree or above was associated with a significantly increased odds of preterm birth and early term birth and a decreased odds of late or post-term birth . Similarly, in the unadjusted model, having some college was associated with a significantly increased odds of preterm birth and a significantly decreased odds of late- or post-term birth . With co-adjustment for other principal exposure variables, effect estimates from the unadjusted model were somewhat attenuated. In the models that were additionally adjusted for maternal age, parity, marital/cohabitation status, and child sex, having a high school degree or less vs. a master\u2019s degree or above remained associated with a significantly increased odds of preterm birth and early term birth . Similarly, in the overall adjusted model, having some college was significantly associated with an increased odds of preterm birth . In the overall adjusted model, having some college vs. a master\u2019s degree or above was also significantly associated with a decreased odds of late or post-term birth .3.3.2For the secondary sample, an increased level of neighborhood deprivation (as indicated by the fourth NDI quartile) was associated with a significantly increased odds of preterm and early term birth in the unadjusted models. This association only remained significant after adjustment for the early term births . In addition, participants with increasing levels of neighborhood deprivation had a significantly increased odds of late or post term birth in the adjusted model.3.3.3Race quartiles vs. the fourth quartile and preterm birth ; however, these findings became non-significant after adjustment for covariates. The unadjusted model showed a significantly increased odds of early term birth among those in the first, second, and third ICERace quartiles, with some attenuation of the effect estimate in the co-adjusted and adjusted models, resulting in some non-significant results. In the unadjusted, co-adjusted, and adjusted models, there was consistently a significantly decreased odds of late or post-term birth among those residing in the first, second, and third ICERace quartiles compared to the fourth quartile .For the secondary sample, the unadjusted model showed a significant association between residence in a census tract in the first and second ICE3.4Race and gestational age at birth after stratification by maternal race/ethnicity.In our primary study population, the association between SES exposure variables and gestational age at birth differed when stratified by maternal race/ethnic category . We obse3.5Race and gestational age at birth after stratification by United States Census Region.Associations between maternal education and gestational age at birth varied by United States Census region . We obse3.6Race with gestational age at birth also did not differ after further adjustment.Estimates that incorporated adjustments for additional covariates related to maternal health conditions and substance use behaviors had a minimal impact on the results regarding the relationship between maternal education and neighborhood deprivation and gestational age at birth . SpecifiRace may be more salient or may reflect that there were relatively few minority participants in the highest education category. Understanding the association between individual- and neighborhood-level factors with gestational age is critical for the identification and targeting of effective solutions to improve maternal and child health and health equity.Race quartile reflecting a lower proportion of non-Hispanic White individuals in the census tract) had an decreased odds of post term birth.In our analysis of the combined effects of individual- and neighborhood-level measures of SES, neighborhood-level measures of SES were not associated with pregnancy duration overall. However, individuals living in more deprived neighborhoods had an increased odds of post term birth, and individuals living in higher racial privilege neighborhoods on gestational age at birth; with the inclusion of these variables in the model, a lower ICERace quartile associated with a decreased odds of preterm birth and attenuated the association with the increased odds of early-term birth. These findings suggest a complex relationship among pre-pregnancy BMI, pregnancy-related conditions, and racial segregation that warrants further investigation. For example, are neighborhoods with a lower proportion of non-Hispanic White individuals more communal or supportive in some way that influences gestational age at birth?Notably, in statistical models that additionally adjusted for maternal health conditions, including pre-pregnancy BMI and pregnancy-related conditions and substance use behaviors, little change occurred in the effect estimates for maternal education level and NDI quartile on gestational age at birth. This observation may suggest that these individual- and neighborhood-level measures of SES exert their influence partly through pathways that are not directly related to maternal health status and/or behaviors, which may include pathways mediated by psychosocial factors, social support and stress, environmental exposures, and access to healthy food and recreation , 64, 65.The relationship between a higher level of maternal education and a lower preterm birth risk has been previously documented in the United States , 51. AltPrevious studies employing neighborhood-level measures of deprivation largely support an association between greater deprivation and preterm birth. In one study, NDI was found to associate with preterm birth in four United States between 1995 and 2001 . LikewisRace-Income) on health outcomes found five studies examining the outcome of preterm birth; these studies support a significant association between higher racialized economic segregation and preterm birth being associated with an increased odds of preterm birth primarily among non-Hispanic Black individuals . A systerm birth . A meta-rm birth . Anotherrm birth . The autA growing body of research has assessed area-based measures of SES in conjunction with environmental exposures to investigate preterm birth from an environmental justice perspective. Such studies have found that exposures to air pollution and water pollution increase the risk for preterm birth, particularly among neighborhoods of low SES . Future 5This study addresses an important gap in the literature, namely the limited data on racial/ethnic and geographic variation in individual- and neighborhood-level measures of SES and gestational age at birth across the United States A strength of the ECHO-wide cohort is its heterogeneity with respect to race/ethnicity, geographic variation covering multiple states and regions, and SES. Another strength of the ECHO cohort data is the availability of maternal prenatal residential addresses, which allowed for geocoding and assignment of neighborhood-level measures of SES at the census tract. Publicly available birth record data does not allow for discernment of geography to the census tract level. Within the published literature, aside from our previously published disseminated meta-analysis , no otheAn additional strength of the ECHO cohort data is the availability and wealth of data on maternal health conditions and pregnancy complications that are linked with gestational age at birth outcomes. This rich data available across the ECHO cohorts offer a unique opportunity to expand on the analyzes of geographic variation in gestational age outcomes based on natality files. Conversely, the heterogeneity of the ECHO cohorts presents limitations. There was considerable variability in the measurement methods of the different variables , thus leading to the potential misclassification of outcomes and exposures.An important limitation of this study and many other studies is that we were unable to examine the duration of exposure to neighborhood deprivation and racial segregation, which would require the construction of longitudinal residential address data over time. Neighborhoods where a mother has lived over the life course, encompassing childhood, adolescence, and adulthood, may have significant effects on health later in life. Living in a poorer neighborhood as a youth may expose a mother to chronic stress that later increases the risk for preterm birth . A studyA further limitation of the present study is the lack of investigation into the effect of interpersonal racial discrimination on gestational age at birth outcomes in the United States A substantial body of research suggests that racial discrimination is an important stressor, especially for Black Americans, and that physiological responses to chronic stress related to interpersonal and systemic racial discrimination contribute to an excess risk of preterm birth . A syste6The findings from this analysis indicate that both maternal education and neighborhood deprivation, representing individual- and neighborhood-level measures of SES, associate with preterm birth in the United States The findings suggest that interventions aimed at reducing preterm birth should include the promotion of higher educational attainment among women of reproductive age and multi-level community initiatives that foster community development. Additionally, the findings reinforce that for some racial and ethnic groups and geographic regions, factors other than higher educational attainment, such as racism, may be more salient exposures such that higher educational attainment and neighborhood privilege are not protective. Thus, interventions are needed that focus on achieving equitable access to the social determinants of health. In particular, there is a need for innovative social and economic policies and programs that support equal benefits from social resources for racial and ethnic minority individuals, including educational attainment. Such policies should focus on optimizing access to resources and assets and reducing societal and structural barriers that hinder racial and ethnic minority populations, including residential segregation and fewer and lower-quality educational opportunities . The CenSelect de-identified data from the ECHO Program are available through NICHD\u2019s Data and Specimen Hub (DASH) . Information on study data not available on DASH, such as some Indigenous datasets, can be found on the ECHO study DASH webpage . Further enquires can be directed to the corresponding author\u2019s.The studies involving humans were conducted in accordance with the local legislation and institutional requirements. The ECHO study protocol was approved by the local and/or central ECHO Institutional Review Board. Written informed consent was provided by the participants\u2019 legal guardians/next of kin .AD, MB, LD, and MM contributed to conception and design of the study. MB and MM organized the database, performed the statistical analysis, and prepared tables and figures of results. AD and MM wrote the initial drafts of the manuscript. All authors contributed data for analysis and contributed to manuscript revision, read, and approved the submitted version of the manuscript.ECHO Components\u2014Coordinating Center: Benjamin DK, Smith PB, and Newby KL, Duke Clinical Research Institute, Durham, North Carolina; Data Analysis Center: Jacobson LP*, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Catellier D and Parker CB*, Research Triangle Institute, Durham, North Carolina; Person-Reported Outcomes Core: Gershon R and Cella D, Northwestern University, Evanston, Illinois.ECHO Awardees and Cohorts\u2014Alshawabkeh AN, Northeastern University, Boston, MA; Aschner J, Albert Einstein College of Medicine, Bronx, New York; Dabelea D. University of Colorado Denver, Denver, CO; Koinis Mitchell D, Deoni S, D\u2019Sa V, Rhode Island Hospital, Providence RI; Duarte CS, New York State Psychiatric Institute, New York, NY; Dunlop AL, Emory University, Atlanta, GA; Elliott AJ, Avera Research Institute, Sioux Falls, SD; Ferrara A, Kaiser Permanente Northern California Division of Research, Oakland, CA; Breton C, University of Southern California, Los Angeles, CA; Hipwell A, University of Pittsburgh, Pittsburgh, PA; Karagas M, Geisel School of Medicine at Dartmouth, Lebanon, NH; Karr C, University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA; Leve L, Prevention Science Institute, University of Oregon, Eugene, OR; Ganiban J, George Washington University, Washington, DC; Weiss ST, Brigham and Women\u2019s Hospital, Boston, MA; McEvoy C, Oregon Health and Science University, Portland, OR; Lyall K, AJ Drexel Autism Institute, Philadelphia, PA; Oken E, Harvard Pilgrim Health Care Institute, Boston, MA; O\u2019Shea M, University of North Carolina, Chapel Hill, NC; Kerver JM, Michigan State University, East Lansing, MI; Herbstman J, Columbia University Medical Center, New York, NY; Schantz S, University of Illinois, Beckman Institute, Urbana, IL; Stanford J, University of Utah, Salt Lake City, UT; Wright RJ, Icahn School of Medicine at Mount Sinai, New York, NY; Huddleston K, George Mason University, Fairfax, VA; Sathyanarayana S, Seattle Children\u2019s Research Institute, Seattle, WA; Gern J, University of Wisconsin, Madison WI; Merhar S, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; Ren C, Indiana University, Riley Hospital for Children, Indianapolis, IN; Reynolds A, University of Buffalo, Jacobson School of Medicine and Biomedical Sciences, Buffalo, NY; Keller R, University of California, San Francisco; Pryhuber G, University of Rochester Medical Center, Rochester, NY; Duncan A, University of Texas Health Sciences Center, Houston, TX; Moore P, Vanderbilt Children\u2019s Hospital, Nashville, TN; Lampland A, Children\u2019s Hospital and Clinic Minneapolis, MN; Wadhawan R, Florida Hospital for Children, Orlando, FL; Wagner C, Medical University of South Carolina, Charleston, SC; Keller R, University of Arkansas for Medical Science; Hudak M, University of Florida College of Medicine, Jacksonville, FL; Mayock D, University of Washington, Seattle, WA; Washburn L, Wake Forest University School of Medicine, Winston Salem, NC; Canino G, University of Puerto Rico, San Juan, PR; Croen L, Kaiser Permanente Northern California Division of Research, Oakland, CA; Detroit, MI and Zoratti E, Henry Ford Health System; Seroogy C and Bendixsen C, Marshfield Clinic Research Institute, Marshfield, WI; Johnson C, Henry Ford Health System, Detroit, MI; Bastain T, Farzan S, and Habre R, University of Southern California, Los Angeles, CA; Mason A, University of Tennessee Health Science Center, Memphis, TN; Women and Infants Hospital of Rhode Island, Providence RI, Lester B; Carter B, Children\u2019s Mercy, Kansas City, MO; Pastyrnak S, Helen DeVos Children\u2019s Hospital, Grand Rapids, MI; Neal C, Kapiolani Medical Center for Women and Children, Providence, RI; Smith L, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles CA; Helderman J, Wake Forest University School of Medicine, Winston Salem, NC; O\u2019Connor G, Boston University Medical Center, Boston, MA; Zeiger R, Kaiser Permanente, Southern California, San Diego, CA; Bacharier L, Washington University of St. Louis, St Louis, MO; Volk H, Johns Hopkins Bloomberg School of Public Health; O\u2019Connor T, University of Rochester Medical Center Rochester, NY; Simhan H, University of Pittsburgh Medical Center, Magee Women\u2019s Hospital, Pittsburgh, PA; Vaidya R, Baystate Children\u2019s Hospital, Springfield, MA; Obeid R, Beaumont Health Medical Center, Royal Oak, MI; Rollins C, Boston Children\u2019s Hospital, Boston, MA; Bear K, East Carolina University Brody School of Medicine, Greenville, NC; Pastyrnak S, Helen DeVos Children\u2019s Hospital, Grand Rapids, MI; Lenski, M, Michigan State University College of Human Medicine, East Lansing, MI; Msall M, University of Chicago, Chicago IL; Frazier J, University of Massachusetts Medical School, Worcester, MA; Washburn, L, Wake Forest Baptist Health , Winston Salem, NC; Montgomery A, Yale School of Medicine, New Haven, CT; Barone, C, Henry Ford Health System, Detroit, MI; McKane, P, Michigan Department of Health and Human Services, Lansing, MI; Paneth N, Michigan State University, East Lansing, MI; Elliott, M, University of Michigan, Ann Arbor, MI; Woodruff T, University of California, San Francisco, San Francisco, CA; Porucznik C, University of Utah, Salt Lake City, UT; Silver R, University of Utah, Salt Lake City, UT; Trasande L, New York School of Medicine, New York, NY; Bosquet-Enlow M, Boston Children\u2019s Hospital, Boston MA; Bush N, University of California, San Francisco, San Francisco CA; Nguyen R, University of Minnesota, Minneapolis, MN; Rochester, NY and Barrett E, University of Rochester Medical Center; Miller R, Columbia University Medical Center, New York, NY."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-023-34359-6, published online 06 May 2023.Correction to: The original version of this Article contained an error in the title of the paper, where the term \u201cco-application\u201d was incorrectly given as \u201cco-inoculation\u201d.In addition, the Article contained an error in the Acknowledgments section.\u201cThe authors thank Yasouj University, Iran, for providing the necessary material and facilities to perform this work and the Deanship of Scientific Research at Umm Al-Qura University, Makkah, Saudi Arabia, for supporting this work by Grant Code (Project Code: 22UQU4310387DSR12). The research fellowship granted by the Alexander von Humboldt Foundation, Bonn, Germany, to AG is also gratefully acknowledged.\u201dNow reads:\u201cThe authors thank Yasouj University, Iran, for providing the necessary material and facilities to perform this work and the Deanship of Scientific Research at Umm Al-Qura University, Makkah, Saudi Arabia, for supporting this work by Grant Code (Project Code: 22UQU4310387DSR002). The research fellowship granted by the Alexander von Humboldt Foundation, Bonn, Germany, to AG, is also gratefully acknowledged.\u201dThe original Article has been corrected."} +{"text": "Protein matters and proteins matter in nutrition and health\u2014why?Protein is one of the three macronutrients for the human body, providing amino acids and building blocks for cell, tissue, and organ maintenance and turnover. Proteins are the \u201cmolecular robots\u201d in living systems implied in controlling, tuning, and executing molecular functions, from gene expression to metabolism.Nutrition and proteomics form a natural merger of health science with bioanalytical technology. Nutrition has the strongest life-long impact on human health, and the science has evolved from elucidating macro- and micronutrient requirements in populations to optimizing diets and delivering functional foods and ingredients for personalized nutrition, all to maintain health, prevent (chronic) disease, and enhance performance and wellbeing.Mass spectrometry-based proteomics and peptidomics are the leading platforms for the comprehensive analysis of proteins and peptides to assess food composition, quality, authenticity, and safety, and to identify biomarkers for nutritional predisposition and intervention. For this Special Issue, studies are collected on cutting-edge science about proteomics and peptidomics technology, including bioinformatics, and their deployment for (a) the analysis of food composition, quality, authenticity, and safety; (b) the identification and characterization of directional food\u2013health relationships; and (c) the discovery and characterization of bioactives with specific health benefits, thereby leveraging food proteins beyond their purely nutritional value.Triticum aestivum. Ana G. Abril and M\u00f3nica Carrera et al. from the University of Santiago de Compostela, and the Spanish National Research Council, Vigo, Spain, present a \u201cproteomic characterization of food-derived anti-allergic and anti-inflammatory peptides\u201d. Mengzhen Hao, Huilian Che, and colleagues from the China Agriculture University, Beijing, identified \u201callergens in Pitaya seeds using proteomics and immunoinformatics\u201d. Finally, Federica Farabegoli, Ignacio Ortea, and Celina Costas et al. from various research institutions across Spain explored \u201canti-inflammatory effects of inulin in a murine macrophage cell model by transcriptomics and proteomics\u201d.Following this scope and logic, I herewith shortly introduce the contributions and the teams behind the work: Sarah Brajkovic, Claus Schwechheimer, Bernhard Kuster, and collaborators at the Technical University, Munich, and the Leibniz University, Leipzig, Germany, describe the technology and methods needed for \u201clarge-scale proteomics in crop plants\u201d\u2014the proteomes that feed the world. Jacqueline Monteiro from the University S\u00e3o Paolo, Brazil, and Jim Kaput et al. from Vydiant Inc., Madison, WI, USA, identified and analyzed \u201ctopic clusters in a nutri-, food-, and diet-proteomic corpus using machine reading\u201d. I report on the \u201cprediction, discovery, and characterization of plant- and food-derived health-beneficial bioactive peptides\u201d. Salvatore Foti et al. from the University Catania, Italy, introduce \u201ca manually curated database of the metabolic proteins of Nutrients editorial team for having made this Special Issue possible and bringing it to life.I hope you enjoy reading these articles, thereby receiving an update on a fascinating field of life science. I would like to thank all contributors, among who are many long-term colleagues and friends, and the"} +{"text": "Camellia sinensis) is now grown commercially in more than 60 countries, where it has made great contributions to local economies [The origins of tea, a traditional beverage in China, can be traced back to the Shennong period, about 2737 years before the birth of Christ . NowadayTea\u2019s long history and widespread popularity can be attributed to its unique and gratifying flavor, along with numerous health benefits such as its anti-oxidant, anti-obesity, and anti-microbial properties . An in-dThere are six categories of traditional tea in China, popularly known as green tea, yellow tea, white tea, oolong tea, black tea, and dark tea. Due to each one having its own specific manufacturing process, in which the degree of fermentation is a decisive factor, they are very different from one another in terms of their sensory appeal and physicochemical properties. For example, green tea, an unfermented tea variety, usually appears green in color both in terms of its leaves and the final infusion, as well as smelling refreshing and having an umami-dominated flavor. Meanwhile, black tea, with its reddish appearance and caramelized flavor, is made by applying full fermentation. Apart from the traditional teas mentioned above, since 2015 a range of \u201cnew tea drinks\u201d have been setting off a burst of enthusiasm among young people around China, even becoming an emerging industry in their own right [A plethora of studies have been conducted to explore associations between tea\u2019s sensory qualities, particularly its flavor, with the chemicals that emerge during tea processing. We have so far detected about 600 volatile components in tea leaves and tea drinks, each of them with different scents, like grassy, woody, floral, etc. . The flaThe healthcare functions of tea come from its rich bioactive ingredients, especially flavonoids. The exploration of tea\u2019s functional components has always attracted a great deal of research interest. The therapeutic potentials of quite a few of tea\u2019s components have been confirmed repeatedly, and the mechanisms involved, such as EGCG, have also been deeply studied. At the same time, however, the limits of these potentials have also been realized; like the low stability and bioavailability of these components, which limit their utilizability. Moreover, figuring out how to extract, separate, and concentrate those bioactive components in an environmentally friendly, low-cost, and high-performance manner is also worthy of focus.We launched this Special Issue of Foods, entitled \u201cAdvances in Tea Chemistry\u201d, with the aim of publishing high-quality research on tea chemistry from a wide range of aspects, including but not limited to the sensory/flavor qualities of tea, tea processing and storage, the extraction, bioactivity, and utilization of functional components from tea, as well as new tea-based beverages or foods. This series will be useful for expanding our understanding of the associations between tea chemistry, flavor, and bioactivity."} +{"text": "Correction: Trials 24, 407 (2023)https://doi.org/10.1186/s13063-023-07394-xFollowing publication of the original article , we haveOriginally published Funding section:Open Access funding enabled and organized by Projekt DEAL. Financial support for the study is provided by PENTAX Medical Europe, Julius-VosselerStra\u00dfe 104, 22527 Hamburg, Germany. Specifcally, an expense allowance of 75 \u20ac will be paid for each patient recruited. In addition, the costs for applying for the ethical vote will be covered by Pentax. No further funding will be provided. The funder has had and will have no infuence on the study design, data collection, data management, data analysis, interpretation of the data, writing of the report, and the decision to submit the report for publication . Specifically, an expense allowance of 75 \u20ac will be paid for each patient recruited. In addition, the costs for applying for the ethical vote will be covered by Helios Kliniken GmbH, Germany. No further funding will be provided. The funder has, had, and will have no infuence on the study design, data collection, data management, data analysis, interpretation of the data, writing of the report, and the decision to submit the report for publication from 31 December 2022.Additional file 3. Contract funder/coordinating study centre (translated in English) from 31 December 2022."} +{"text": "Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU By Chongcharoenyanon T, Samransamruajkit R and Sophonphan J. (2023) Front. Pediatr. 11:1167595. doi: 10.3389/fped.2023.1167595A Corrigendum on Error in Author ListIn the published article, there was an error in the author list, and authors Jiratchaya Sophonphan and Rujipat Samransamruajkit are in the incorrect order. As a result the order of affiliations have also changed. The corrected author list and affiliations appears below.1, Rujipat Samransamruajkit2, Jiratchaya Sophonphan3Tatchanapong Chongcharoenyanon1Division of Pulmonology, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2Division of Pediatric Critical Care, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 3The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, ThailandThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.Error in CorrespondenceIn the published article, there was an error in the correspondence, and author Tatchanapong Chongcharoenyanon was stated as the corresponding author. The correct corresponding author appears below.rujipatrs@gmail.comRujipat Samransamruajkit, The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "New cytotoxic agents and regimens, as well as immunotherapeutics, have recently been introduced for treatment of colorectal cancer (CRC).To identify the patient-related and clinical and treatment-related factors associated with higher total health care expenditures in newly diagnosed patients with CRC who are receiving systemic therapy (biologic or chemotherapy) from a commercially insured population.A longitudinal, retrospective analysis was employed to estimate costs and determinants of CRC treatment in a U.S. claims database for health care services used by commercial patients aged 18 to 64 years, who were diagnosed with CRC between January 1, 2005, and June 30, 2009. Generalized linear regression modeling was used to estimate the influence of demographic, clinical, and treatment factors on medical expenditures.Among the 5,160 patients newly diagnosed with CRC, 99.6% of patients had chemotherapy; 32.6% had biologics; and 85.6% had other pharmaceuticals (excluding the chemotherapy and biologics of interest). The average annualized per patient cost of CRC treatment was $97,400 and consisted of chemotherapy , biologics , other pharmaceuticals , inpatient treatment , and outpatient treatment . From first line only, first and second lines only, and third+ lines, the cost per patient was $70,500, $100,100, and $152,900, respectively. After adjusting for health care inflation, the average treatment cost of CRC patients increased by 73% from 2005 to 2009. Adjusted analyses showed that the higher medical cost for CRC patients was associated with use of new regimens, metastasis, comorbidities, surgery, radiation, insurance plan, age, sex, and region.The health care cost of CRC treatment is increasing significantly over time, which is most likely caused by the use of new regimens, higher chances of surgery and radiation, and occurrence of various comorbidities and metastatic diseases due to increasing survival time."} +{"text": "Psychosis is a frequent complication in patients diagnosed with Parkinson\u2019s Disease (PD). Characterized mainly by visual hallucinations and paranoid delusions, it occurs most frequently, but not exclusively, as an adverse effect of antiparkinson medications. Nevertheless, cognitive impairment and dementia, as a frequent feature of PD, needs to be considered for differential diagnosis.Our main objective is to report a case of PD Psychosis, its diagnosis and management and complement it with a non-systematic review of literature.Patient file consultation and an additional research, based on the key words \u201cPsychosis\u201d and \u201cParkinson\u2019s Disease\u201d, using Pubmed as database.A 53-year-old female, diagnosed with Juvenile Parkinson\u2019s Disease since age 45 and, as expected, polimedicated with antiparkinson medication. Without any relevant psychiatric background, she was admitted to the emergency department for disorganized behaviour, with 2 weeks of evolution. There, it was also possible to determine the presence of auditive hallucinations and persecutory delusions, associated with marked anguish.After exclusion of any underlying cause for this symptomatology, inpatient treatment was proposed and accepted by the patient. In collaboration with the Neurology Department, a gradual reduction and optimization of antiparkinson drugs was conducted, associated with introduction of low doses of antipsychotic drugs, in this case Olanzapine. With this medication adjustments, clinical improvement was accomplished, with eventual fading and cessation of psychotic symptoms. Additionally, an irregularly intake of antiparkinson drugs was considered the most probably cause of this clinical decompensation.As present in literature, due to the chronicity and complexity of PD, stopping all antiparkinson drugs is not an option, even when psychotic symptoms, that could be a consequence of these drugs, are present. Therefore, a rigorous evaluation and management are mandatory, including the exclusion of other underlying causes and a careful therapeutic adjustment, with gradual reduction of antiparkinson drugs, addressing an eventual temporal relationship between the beginning of a specific drug and the onset of symptoms, and verification of therapeutic compliance, including an involuntary overdose. In cases of refractory symptoms, and after a risk-benefit assessment, pharmacologic treatment directed at these symptoms, low doses of anti-psychotics, may be necessary.None Declared"} +{"text": "An affiliation for the second author was incorrectly omitted. In addition to institution number 1, Mingying Song is also affiliated to the following institution: Department of Physics, QMUL, Mile End Road, London E1 4NS, UK."} +{"text": "Alvania spp. in the first site, and of Alvania and Schwartziella at Cape Verde. In spite of the large number of rissoids at Madeira archipelago, a large number of species are shared with Canaries, Selvagens, and the Azores, thus only about 8% are endemic to the Madeira archipelago. Most of the 542-rissoid species that live in the Atlantic and in the Mediterranean are shallow species (323), 110 are considered as deep species, and 23 species are reported in both shallow and deep waters. There is a predominance of nonplanktotrophs in islands, seamounts, and at high and medium latitudes. This pattern is particularly evident in the genera Crisilla, Manzonia, Onoba, Porosalvania, Schwartziella, and Setia. Planktotrophic species are more abundant in the eastern Atlantic and in the Mediterranean Sea. The results of the analysis of the probable directions of faunal flows support the patterns found by both the Parsimony Analysis of Endemicity and the geographical distribution. Four main source areas for rissoids emerge: Mediterranean, Caribbean, Canaries/Madeira archipelagos, and the Cape Verde archipelago. We must stress the high percentage of endemics that occurs in the isolated islands of Saint Helena, Tristan da Cunha, Cape Verde archipelago and also the Azores, thus reinforcing the legislative protective actions that the local governments have implemented in these islands during the recent years.The geographical distribution of the Rissoidae in the Atlantic Ocean and Mediterranean Sea was compiled and is up-to-date until July 2011. All species were classified according to their mode of larval development (planktotrophic and nonplanktotrophic), and bathymetrical zonation . 542 species of Rissoidae are presently reported to the Atlantic Ocean and the Mediterranean Sea, belonging to 33 genera. The Mediterranean Sea is the most diverse site, followed by Canary Islands, Caribbean, Portugal, and Cape Verde. The Mediterranean and Cape Verde Islands are the sites with higher numbers of endemic species, with predominance of Rapoport's latitudinal rule relates geographical distribution with latitude , 2. ThisAlthough studies relating biological diversity with latitude usually use higher taxonomical categories, recent papers restricted to checklists of marine molluscs have been used to address this issue \u201312. The The Rissoidae are a family of small-sized, marine to brackish-water gastropod molluscs. This very diverse family was taxonomically reviewed by Wenz , Coan 1, NordsiePublished information about the Atlantic and Mediterranean Rissoidae is vast and is scattered among a wide variety of journals but, with a few exceptions, these studies are typically geographically localized. Many species descriptions are usually based on shell morphology and on only a few specimens, most of them dead shells. At present, there is a lack of a background scenario of the geographical distribution for this family in the Atlantic and in the Mediterranean. No phylogeny has been established for this family.To our knowledge, this is the first attempt to summarize present information about the geographic distributional pattern of this family in the Atlantic Ocean and the Mediterranean Sea, with the purpose of identifying the biotic similarities between areas. The geographical distribution of the Rissoidae in the Atlantic Ocean and Mediterranean Sea was compiled through an exhaustive search of the primary literature and is up to date until July 2011. The following sites and references were considered:- ARC: Arctic: above 75\u00b0\u2009N: War\u00e9n , 25, Han- GRE: Greenland, western shores of Baffin Island, Baffin Bay, Davis Strait, and Labrador Sea: Bouchet and War\u00e9n , Hansson- ICE: Iceland: War\u00e9n , 29,- SCA: Scandinavia: Norway Sea, Skagerrak and Kattegat, Baltic Sea and Faroe Islands: Fretter and Graham , War\u00e9n , 29, Han- BRI: British Isles: Smith , Fretter- POR: western Atlantic Iberian fa\u00e7ade and southern shores of Algarve, Portugal): Nobre , 34, Nob- MED: Mediterranean: Nordsieck , Aartsen- AZO: Azores: Watson , Dautzen- LUS: Lusitanian group of seamounts : Gorringe, Josephine, Amp\u00e8re, Seine: \u00c1vila and Malaquias , Beck et- MET: Meteor group of seamounts (located about 600\u2009km south of the Azores): Great Meteor, Irving, Atlantis, Hy\u00e8res, Plato, Tyro, Cruiser: Gofas , - MAD: Madeira, Porto Santo and Desertas Islands, Nobre , van Aar- SEL: Selvagens Islands: Verduin , Amati ,- CAN: Canary Islands: van Aartsen , Moolenb- CAP: Cape Verde archipelago: Rol\u00e1n , Moolenb- STH: Saint Helena Island: Smith , MALACOL- TRS: Trist\u00e3o da Cunha Island: Worsfold et al. , MALACOL- WAF: West African shores\u2014Atlantic Morocco, from Straits of Gibraltar south, Western Sahara, and Mauritania, Cape Verde : Verduin , Gofas a- ANG: Angola: Rol\u00e1n and Ryall , Rol\u00e1n a- NSC: New Scotia biogeographical province\u2014Atlantic shores of USA, between Newfoundland (50\u00b0\u2009N) and Cape Cod (42\u00b0\u2009N): MALACOLOG,- sensu Engle and Summers [VIR: Virginian biogeographical province Summers \u2014Atlantic- CRL: Carolinian biogeographical province\u2013Atlantic shores of USA, between Cape Hatteras, North Carolina (35\u00b0\u2009N) and Cape Canaveral (28\u00b030\u2032\u2009N): Rex et al. , MALACOL- TRO: Tropical biogeographical province \u2014Atlantic shores of USA, south of Cape Canaveral (28\u00b030\u2032\u2009N), including western and eastern shores of Florida, Gulf of Mexico , Bahamas, Caribbean Sea, south to Cabo Frio (Brazil) (23\u00b0S): Dall , Baker e- sensu Palacio [BRA: Biogeographical province of Brazil \u2014from Ca- sensu Palacio [SSA: southeast of South America\u2014biogeographical province of Malvinas Atlanti Palacio , Ponder Palacio ,- ANT: Antarctic\u2014from 60\u00b0S south, including South Orkney Islands (Signy Island), South Shetland islands, Antarctic Peninsula and Weddell Sea: Ponder . We have also consulted other bibliographical sources, with a wider systematical or geographical subject, such as Babio and Thiriot-Qui\u00e9vreux , AartsenThe bathymetrical zonation considers shallow species and deep species . The choice of the threshold at 50\u2009m depth is related with the following reasons: (i) algal species to which Rissoidae are very often associated are rare below 50\u2009m depth; (ii) direct sampling by scuba-diving is more frequent in waters less than 50\u2009m depth; (iii) in waters deeper than 50\u2009m depth, usually the samplings are obtained via indirect methodologies .The complete database was last updated in October 2011 and is available from the authors upon request. \u03bcm) and with several whorls , are associated with a planktotrophic mode of larval development. In most of the planktotrophic species, it is possible to discern between protoconch I and protoconch II. This is especially evident in species that possess a \u201csinusigera\u201d larva, as is the case of Alvania cancellata [\u03bcm, typically more than 300\u2009\u03bcm [All species were classified according to their mode of larval development and bathymetrical zonation. Rissoids lay ovigerous capsules in the substrate that originate larvae with different modes of larval development. The extension of the larval phase reflects on the capabilities of dispersal and this has important ecological and historical biogeographical implications, related with the geographical distribution of the species. Two types of larval development were considered: planktotrophic (with a free-swimming feeding stage) and nonplanktotrophic , 153. Asncellata . Paucispn 300\u2009\u03bcm , and witn 300\u2009\u03bcm , 155\u2013157Rosen and Smith developeAlvania dorbignyi [Rissoina bertholleti, Rissoina spirata , and Voorwindia tiberiana [Four species considered as Lessepsian and thus reported to the Mediterranean were removed from the initial database: orbignyi , Rissoiniberiana . Unique iberiana . No cosmiberiana , 164. Triberiana includiniberiana ), measurXA and XB) for each pair of areas (A and B) [The analysis of the historical relationships between the selected areas was complemented by using the following formulas (A and B) :A is the total number of rissoid species present in area A, and B is the total number of rissoid species present in area B. When a faunal flow happened in historical times, from a source area to the target area, we expect the target area to show a subset of the species present in the source area. So, different values of the two indices (XA and XB) are expectable, and the source area must have the smaller value [er value .Manzonia, Rissoina, Zebina, Stosicia, Pusillina, and Alvania), while others are geographically restricted. According to Ponder [Attenuata, Lamellirissoina, Lironoba, Lucidestea, Merelina, Parashiela, Striatestea, and Voorwindia are restricted to the Indo-Pacific. However, Leal [Lironoba from Brazil . Some genera solely occur in the Indian Ocean, for example, Fenella (Madagascar and Red Sea), while the genera Tomlinella is restricted to Reunion Island and Mauritius and the recently described Porosalvania is restricted to the Meteor group of seamounts [ Rissoidae family comprises 47 valid genera, some with a worldwide distribution , a widespread planktotrophic deep species; Lironoba sp., a nonplanktotrophic species restricted to the Atol das Rocas [Galeodinopsis tiberiana , a shalstrigata , a speciiberiana , a shallThe Mediterranean Sea is the most diverse site, with 160 species of Rissoidae, followed by Canary Islands (89 species), Caribbean (77), Portugal (74), and Cape Verde (67). The lowest diversity sites are the Carolinian Province (18 species), Greenland (16), Arctic (13), Angola (11), New Scotia Biogeographical Province (10), Antarctic (8), Virginian Biogeographical Province, Tristan da Cunha Island, and Brazil , Rissoa (26), Setia (18), and Pusillina (11) are species-abundant in the Mediterranean and along the Portuguese shores. Boreocingula and Frigidoalvania (as the name indicates) are restricted to higher latitudes . Boreocingula also occurs in the British Isles, and Frigidoalvania is reported to the Atlantic shores of North America (NSC and VIR). Onoba is a genus with high number of species at Iceland and Greenland , but the most diverse sites are in the South Atlantic: 22 species at southeast of South America and 6 species at Tristan da Cunha Island and Antarctic . Crisilla and Manzonia are particularly species-diverse in the Macaronesian archipelagos, especially at Canary Islands, Selvagens and Madeira, Porto Santo, and Desertas Islands. Manzonia is a specious genus also at the Lusitanian group of seamounts. Schwartziella spp. is very abundant at Cape Verde archipelago (26 species) as well as in the Carolinian and Tropical Provinces, and at Saint Helena Islands . Porosalvania is a newly described endemic genus to the Meteor group of seamounts where it radiated into a number of species . However, fossil species of Stosicia are known from the Lower Miocene of the Eastern Atlantic and the Mediterranean [c Region , with juaberrans , and Stoubricki in the first site, and of Schwartziella (26) and Alvania (20) at Cape Verde. Caribbean also has a high number of endemisms (57 species), especially of the genera Alvania (19) and Rissoina (13). British Isles, Angola, New Scotia, and Virginian Provinces do not have endemic species, and Brazil, Greenland, and Scandinavia only possess a single endemic species , with predominance of species . However species .In spite of the large number of rissoids at Selvagens (38 species), a large number of species are shared with Canaries (30) and Madeira (27) , thus on Most of the 542-rissoid species that live in the Atlantic and in the Mediterranean are shallow species (329). One hundred and forty-six are considered as deep species, living in waters with more than 50\u2009m depth, and 23 species are reported to both shallow and deep waters. It was not possible to establish the bathymetrical zonation of 44 rissoid species.Benthonella, Benthonellania, Frigidoalvania, Gofasia, Microstelma, and Pseudosetia typically are deep species, whereas Botryphallus, Crisilla, Manzonia, Peringiella, Pusillina, Rissoa, Rissoina, Rudolphosetia, Schwartziella, Setia, and Zebina are mostly constituted by shallow species. Some of these genera are exclusively littoral. In the eastern-Atlantic shores and at latitudes higher than 55\u00b0\u2009N , Alvania genus is mostly made of deep species; in all the other sites, usually this genus is predominantly dominated by shallow species ;shallow planktotrophic rissoid species are much more diverse along the European Atlantic shores, the west-African shores, the Mediterranean, and the Caribbean than in the Atlantic islands, with the exception of Canaries ;Scandinavia, British Isles, Portugal, Angola, and the Carolinian Province are the only sites with higher numbers of shallow planktotrophic species relative to the number of shallow non-planktotrophs , 115 shallow species and 41 deep species of rissoids were analysed with the PAE methodology, using PAUP*.L = 180, Ci = 0.6389, Ri = 0.7005) with three main groups. The first one strongly clusters Portugal, the Mediterranean, British Isles, and Scandinavia, with bootstrap values higher than 91%. A second group subdivides in two: the first subgroup, the Macaronesian archipelagos of Madeira, Canary Islands, Selvagens, and the Azores clusters; the second subgroup has West-African coast, Angola, and Cape Verde Islands. In a third group, western Atlantic sites are clustered: Caribbean and Carolinian Province cluster to Brazil at 65% bootstrap value. Saint Helena Island weakly clusters to the previous sites . New Scotia and Virginian Provinces cluster in an independent group (66%), as well as Southern South America and Antarctic (95%) .L = 82, Ci = 0.5000, Ri = 0.5816) that results from the PAUP* analysis of the deep rissoids is given in The consensus tree . This is By contrast, the low number of rissoids on the Virginian Province (only 7 species) is probably related with the predominance of sandy bottoms on the littoral of this biogeographical Province, and with the multiple lagunar and estuarine systems, which are inhospitable to the benthic algae where many species of these micromolluscs live . Van Rei By definition, \u201ca species can be endemic to an area for two different reasons: (a) because it has originated in that place and never dispersed, or (b) because it now survives in only a part of its former wider range\u201d . We do nAlvania, Crisilla, Onoba, Pusillina, Rissoa, and Setia at the Mediterranean; Benthonellania and Rissoina at the Caribbean; Manzonia and Crisilla at the Madeira, Selvagens, and Canaries archipelagos; Crisilla and Schwartziella at the Cape Verde archipelago; Onoba at Iceland; and Cingula at the geographically isolated Saint Helena Island. In some areas, a few genera went through a speciation process that led to a high number of both species and endemics, for example, Mironov proposedAX andB X indices) point to a faunal breakdown zone between Cape Verde archipelago and the nearest areas, with very weak relationships with the Canary Islands (7%) and West-African shores (14%), and a little bit higher similarities with Angola (27%). We must stress the high percentage of endemics that occur in the isolated islands of Saint Helena, Tristan da Cunha, and at Cape Verde archipelago (more than 85% of endemics), and also at the Azores (44.7%) thus reinforcing the legislative protective actions that the local governments have implemented in these islands during the recent years. The Cape Verde islands probably received the first rissoids from West-African shores, from where it distances nowadays just about 500\u2009km but must have undergone a long period of isolation, which explains such a high number of endemics. Also, our results are known since the Early Miocene (Eggenburgian) of the Central Paratethys [Rissoa, Manzonia, and Alvania) are similar to their extant Mediterranean and NE Atlantic congeners, and, interestingly, all of these species possess a planktotrophic mode of larval development [ The first fossil record of the Rissoidae family is from the lower Jurassic of the Tethys Sea , 208 andratethys . The proelopment . The ancestral of the Rissoidae presumably had a planktotrophic mode of development . JablonsAlvania africana/A. beani, Alvania marioi/A. cancellata, Alvania gofasi/A. zetlandica, and Crisilla transitoria/C. semistriata.In the absence of a phylogenetic analyses for this family, one can only speculate that during geological times, the ancestral(s) (either planktotrophic or nonplanktotrophic) dispersed, reached an oceanic island by natural means [As it is not possible to invert the loss of the planktotrophic phase, in a relatively short interval, the planktotrophic ancestral may originate one or several species, by adaptive radiation, each species occupying a different niche. This promotes the increase of the number of nonplanktotrophic species, usually with a restricted range of dispersion . Several examples are known from oceanic islands that elucidate the above-mentioned mechanisms: at Madeira, Selvagens, and Canary Islands, the rissoid genera examples . Similarspecies) , 226. Currently, we are unable to choose between the following hypotheses:colonization by an ancestral (either planktotrophic or nonplanktotrophic), followed by speciation with adaptive radiation;several independent colonizations, spaced in timed, by an ancestral that originates a different species, without adaptive radiation;both hypotheses above described.sensu strictum\u201d: Azores, Madeira, Selvages, and Canaries), all computed pairs of areas show low relationships , especially during the sea level low stands associated with the Pleistocene glacial periods , 198, ousensu strictum\u201d Macaronesian archipelagos (Azores, Madeira, Selvagens, and Canaries archipelagos, Another interesting feature is the isolation of the Cape Verde archipelago, which is very weakly related with the \u201c"} +{"text": "Correction to: British Journal of Cancer (2011) 104, 1822\u20131827; doi:10.1038/bjc.2011.154When originally published earlier this year in Volume 104, the authorship of this paper was incorrect. O Kirichek who is based, along with several of the other authors at Department of Medical Oncology, University of Oxford, Churchill Hospital, Oxford, UK, was omitted from the author list.The full author listing is now shown, above. The authors would like to apologise for this mistake."} +{"text": "We want to share a happy development with you. On March 15, 2005, we set up the Mensanamonographs E-group. Within a span of two months, it had already crossed the half-century mark. It now has a seventy plus membership from all over India, and a number of oversees members too. Some prominent mental health specialists, medical professionals, researchers, educationists, and socially conscious members of society are its members. It's a no-obligations group, which even you can join where we can discuss issues concerning medicine, psychiatry, philosophy, religion, science, man and society. The only condition is \u2018an honest effort to appreciate the others point of view and to indulge in a healthy give and take of ideas\u2019.This is its home page:Mensanamonographs is an open forum to discuss psychiatric/ biomedical/ psychological/ philosophical consequences of social disorders/ issues and current events based on evidence and research studies. It is meant to provide a wide platform for serious discussion for psychiatrists, other medical scientists and clinicians, social scientists, philosophers, psychologists, sociologists, and other thinkers interested in exploring social issues with methodological rigour.Mensanamonographs is mainly interested in discussing issues concerning Psychiatry, Philosophy, Medicine, Science, Religion, Man and Society.It does not espouse any particular ideology or school of thought but invites discussion between scholars and the lay intelligent socially conscious members of all societies and cultures to discuss every possible issue under the sun but based on evidence and a healthy give and take of ideas. It encourages enquiry, openness of mind, and the ability to express and imbibe thought.Freedom of thought and expression with social commitment and the openness to discuss a wide array of subjects that concern man and society today regardless of ideological/ institutional/ political/ civilizational affiliations is its motive.All interested in honest open discussion on a wide variety of topics are welcome.If you think you enjoy serious discussion over issues and have some interesting views to share, why don't you join our mensanamonographs group where we attempt to discuss issues concerning medicine, mental health, philosophy, religion, science, man and society?We do not think it is necessary for us to agree on everything.Or on anything for that matter.The only condition is an honest effort to appreciate the others point of view and to indulge in a healthy give and take of ideas.The messages are not so many as to be overwhelming, and the group membership is moderated.http://mensanamonographs.tripod.comRelated Link: mensanamonographs-subscribe@yahoogroups.comSubscribe: http://groups.yahoo.com/group/mensanamonographs/It has discussed a wide range of issues including Mental Health, Creativity, Delusions, Immunization, Thinkers in Mental Health, God, Religion, Terrorism, Bioethics, Ghazals, Einstein, Education, Buddhism, Pharmaceuticals, Suicide, Psychiatry and its Critics, Western and Indian Cultures, Patents, Implants etc. You can browse details at We would strongly recommend you visit it. And if you enjoy debates and discussion, and want to keep yourself intellectually stimulated, join it.www.msmonographs.org \u2022 http://mensanamonographs.tripod.com.We also have a website, which is worth a visit. All Monographs are available, free access on line, full text, at: We would surely welcome any feedback you may offer, by post or email:Correspondence:Dr. Ajai R. SinghEditor, MSM,Mens Sana Research Foundation14, Shiva Kripa, Trimurty Road, Mulund, Mumbai, Maharashtra, India. 400080.mensanamonographs@yahoo.co.ukEmail: Meanwhile, all the best.Editors, MSM"} +{"text": "Jocelyn Anne Rankin, PhD, (figure) chief of the Information Center at the Centers for Disease Control and Prevention (CDC), died on September 19, 2010, at age 63 in her Florida home. Similar to the health professionals in the organization M\u00e9decins Sans Fronti\u00e8res, Jocelyn was a humanitarian and a librarian sans fronti\u00e8res. Although some make a difference by what they do, others, like Jocelyn, also make a difference by how they do it. She was a true leader and a mentor to many librarians throughout the nation. These colleagues will remain profoundly grateful for her contributions to the world of information science, and will, just as deeply, cherish memories of how she made her professional mark\u2014quietly, respectfully, and selflessly, yet with clear vision, determination, and passion. Born in Raleigh, North Carolina, USA, Dr Rankin achieved an education without borders as well: high school in Germany, a diploma in liberal arts from the American College in Paris, a BA cum laude in English from Hollins College in Virginia, an MLn in librarianship from Emory University in Atlanta, and a PhD in educational leadership from Georgia State University in Atlanta. Dr Rankin's career began at the Medical College of Georgia, Augusta, and continued at Georgetown University Medical Center, Washington, DC, and at Mercer University School of Medicine, Macon, Georgia. She designed and led the Georgia Interactive Network for Medical Information, the oldest statewide network of its kind in the nation. At CDC, she led in the creation of a state-of-the-art information center; guided implementation of an integrated, electronic information delivery system; helped create the US Department of Health and Human Services Library Consortium; and most recently, helped build the foundation for CDC\u2019s Science Clips, a weekly digest of selected news pertinent to the public health community. Dr Rankin\u2019s contribution as book review editor for Emerging Infectious Diseases was also highly valued.She leaves behind many who feel privileged to have known her. We offer our condolences to her husband, William Rankin; daughters, Stephanie Smith and Kimberley Macdonald; son, William Rankin III; brother, Howell Cobb; and 2 grandchildren."} +{"text": "Crocus sativus L. (a member of Iridaceae family) has a distinct color, flavor and smell. It is widely used as a spice, and as a coloring and flavoring agent in the preparation of foods and cosmetics. According to chemical analysis, more than 150 chemicals are present in saffron stigmas among which, the three main chemical compounds including crocins , picrocrocin , and safranal are responsible for saffron exclusive color, taste, and odor, respectively , cardiovascular system , central nervous system , eye disease , gastrointestinal system , genitourinary system , infection disease , respiratory system , skin disease , and miscellaneous . Saffron"} +{"text": "What Medicine Means To Me is a first in many ways for MSM. This is the first Theme Monograph. It is also the first Monograph which has contributions from the Asian, Australian, American and African continents.Donelson Dulany, Professor of Psychology Emeritus at the University of Illinois and Editor, American Journal of Psychology, writes on, \u2032What Psychology Means To Me\u2019 (p36 ).Sunil K. Pandya, who writes on \u2018Where is Medical Practice In India Heading?\u2019 (p50) and also on \u2018Turning Points In My Medical Career\u2019 (p154 ), is a Neurosurgeon and from the Dept of Neurosurgery, Jaslok Hospital And Research Center, Mumbai, India. He is also Editor Emeritus, Indian Journal Of Medical Ethics, and on the International Advisory Board of MSM.Shaukat Ali Jawaid, who writes on \u2018What Medicine And Medical Journal Editing Mean To Me\u2019 (p62 ), is Chief Editor, Pulse International, and Managing Editor, Pakistan Journal of Medical Sciences, Karachi, Pakistan.Adamson S. Muula, who writes on \u2018Medicine and Money: Friends Or Foe?\u2019 (p78 ) is from the Department of Community Health, University of Malawi, College of Medicine, Malawi and Department of Epidemiology, University of North Carolina at Chapel Hill, United States.Vance W. Berger, from the National Cancer Institute, Bethesda, MD, USA, and J. Rosser Matthews, from the Virginia Commonwealth University, write on, \u2018What Does Biostatistics Mean to Us\u2019 (p89).Morten Hesse, who writes on \u2018What Does Addiction Mean to Me\u2019 is from Aarhus University, Centre for Alcohol and Drug Research, K\u00f8bmagergade 26E, DK-1150 Copenhagen (p104).S.C. Panda, who writes on \u2018Medicine: Science or Art?\u2019 is Assistant Professor, Department of Community Medicine, V.S.S. Medical College, Burla, Orissa, and Editor, Journal of Community Medicine (p127).Roy Sugarman, Acting Director of Psychology at Royal Rehabilitation Centre in Sydney, and Conjoint Senior Lecturer in Psychiatry at the University of New South Wales, writes on, \u2018What Psychology Means to Me\u2019 (p139).J. K. Trivedi, Professor, Department of Psychiatry, and Dishanter Goel, Junior Resident, both from the King George's Medical University, Lucknow, India, write on, \u2018What Psychiatry Means To Us\u2019 (p166). JKT has also been Past Editor, Indian Journal of Psychiatry, Past President, Indian Psychiatric Society, and is a Member of the International Advisory Board of MSM.S. Malhotra and N. Shafiq, from the Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, write on, \u2018What Clinical Pharmacology Means to Us\u2019 (p184).Ajai R. Singh, Editor and Shakuntala A. Singh, Deputy Editor, MSM, write Editorials on \u2018To Cure Sometimes, To Comfort Always, To Hurt The Least, To Harm Never\u2019 (p8), \u2018Psychiatrists And Clinical Psychologists\u2019 (p10), and \u2018What Is A Good Editorial?\u2019 (p14), besides writing for the Looking Mirror, \u2018A look at CMAJ: A Misty Image Indeed\u2019 (p21). Ajai R. Singh also writes Musings (p18), and in MSM Poems (p208).Avinash De Sousa, Consulting Psychiatrist, Mumbai, writes an Obituary for his mother in, \u2018Dr. Mrs. Dhanalakshmi De Sousa.1938\u20132005.A Tribute\u2019 (p211).K.P. Dave, retired Head, Dept. of Psychiatry, L.T.M.G. Medical College and Hospital, Sion, Mumbai, India, also writes an obituary on \u2018Dr. Mrs. Dhanalakshmi De Sousa (p213).The writings present a rich and varied fare for the serious reader."} +{"text": "The affiliations for all authors are incorrect. The first three authors are affiliated only with institution number 1, Milano-Bicocca University, Dept. of Geological Sciences and Geotechnologies, Milano, Italy, and not with institution number 2, and the last two authors are only affiliated with institution number 2, Senckenberg am Meer, Marine Research Department, S\u00fcdstrand, Wilhelmshaven, Germany, and not with institution number 1."} +{"text": "The first three authors, James R. Petrie, Thomas Vanhercke, and Pushkar Shrestha, should be noted as contributing equally to this work."} +{"text": "Interest and participation in EcoHealth and One Health approaches have grown considerably over the past decade. Clearly, the two approaches have many similarities and strive for similar outcomes, and collaboration between them holds great potential value. Convergence of the two approaches could avoid repetition, strengthening both communities yet still highlighting the unique attributes of each approach. In 2011 Margot Parkes, then President of the International Association for Ecology and Health , called for critical reflection on directions for ecohealth as a transdisciplinary field positioned among converging efforts Parkes . Buildinwww.ecohealth.net). Others have documented the evolution of the field of ecohealth , but not its focus. Ecohealth could further enhance these efforts by drawing on the One Health expertise and experiences in zoonotic disease research, and disease economics, surveillance and management.While One Health is growing in disciplinary diversity, veterinarians and public health practitioners currently form the majority of the field, and it tends to focus on communicable disease, food safety, nutrition and antimicrobial resistance, issues squarely at the nexus of human and animal health. There are gains to be made in synergizing with the already-diverse membership in Ecohealth. The threat of a global influenza pandemic gave great impetus to the One Health movement, and was able to influence the World Organization for Animal Health (OIE), the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) to formally work together under the banner of One Health. Similar collaborations were established in many countries, influencing national policies, investments and research funding. Ecohealth affiliates could learn from the strategies and networks used by One Health advocates to widen their influence on large-scale policy processes.EcoHealth, and with communities of practice in Ecohealth around the world, individuals who identify with the One Health movement gain new platforms for interaction and outreach.One Health has chosen not to have an organisational structure, a single journal for research or policy dissemination, or undertake regular conferencing arrangements. By partnering with existing structures such as the IAEH and its journal, Ecohealth and One Health share many values and approaches, and converge most obviously in the areas of zoonoses, disease emergence, and pandemic threats. Each has strengths to offer the other and by working together, greater impact may be achieved in global health and sustainability. Each also embraces themes and approaches not currently suited to the other. These differences should not prevent a closer interaction; rather, both communities stand to gain from shared information, resources and collaborative action. For example, Ecohealth, with its foundations in environmental issues, could contribute to the enhanced development of ecosystem approaches in One Health. Similarly, One Health could bolster the animal health research in EcoHealth as well as strengthen its economic evaluations and policy influence.Some organizations are already employing the strengths of both approaches. For example, the Centre Suisse de Recherches Scientifiques in C\u00f4te d\u2019Ivoire uses One Health approaches for diseases at the human-animal interface or food borne disease, and Ecohealth approaches for research on climate change, water and vector borne diseases.EcoHealth.Multiple benefits may be gained by bringing together One Health and Ecohealth, yet many people working in one or the other field are unaware of the potential for collaboration. Opportunities abound for reversing this: for example, through joint conferences, shared training, and publication in journals read by both communities of researchers, such as Jakob Zinsstag (convener), Swiss Tropical and Public Health Institute, University of Basel, SwitzerlandMartyn Jeggo (convener), Australian Animal Health Laboratory, CSIRO, AustraliaEsther Schelling, Swiss Tropical and Public Health Institute, Basel, SwitzerlandBassirou Bonfoh, Centre Suisse de Recherches Scientifiques en C\u00f4te d\u2019IvoireDavid Waltner-Toews, University of Guelph, Ontario, CanadaStefano Lelii, Institute of Public Health, Ruprecht-Karls-University, Heidelberg, GermanyBob Williams, Wellington, New ZealandMahamat Bechir, Centre de Support en Sant\u00e9 Internationale, ChadFelix Li, Public Health Agency of Canada, Canadian Embassy, ChinaDominique Charron, International Development Research Center, Ottawa, CanadaRobinson Mdegela, Sokoine University of Agriculture, TanzaniaMeredith Barrett, Robert Wood Johnson Foundation Health and Society Scholars, University of California, San Francisco and University of California, Berkeley, CA, USARichard Kock, Royal Veterinary College, Hertfordshire, United KingdomIbrahima Sy, Swiss Tropical and Public Health Institute, Basel, SwitzerlandAlain Vandersmissen, European Union - European External Action Service, Brussels, BelgiumPeter Black, Department of Agriculture, Fisheries and Forestry, Barton, ACT, AustraliaPeter Daszak, EcoHealth Alliance, New York, USA"} +{"text": "Background. Specific dietary components have been associated with gastroesophageal reflux disease (GERD) in Europe and the United States. However, the relationship between dietary components and GERD in Chinese still remains unclear. Methods. A total of 268 patients who were newly diagnosed as reflux esophagitis (RE) in Outpatient Endoscopy Center of Tongji Hospital were recruited. In addition, 269 sex- and age-matched subjects were also recruited as controls. The body measurements were determined, and the dietary intake during the previous year was evaluated using food frequency questionnaire (FFQ). Stepwise multiple logistic regression analysis was performed to examine the association between nutrients and RE. Results. After adjustment for WC, WHR, total energy intake, and demographics, there were a positive dose-response relationship between RE and calcium, meat, oils, and salt and a negative dose-response relationship between RE and protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs. Conclusion. High intake of meat, oils, salt, and calcium is associated with an increased risk for RE while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for RE. Gastroesophageal reflux disease (GERD) is a chronic disease usually caused by the reflux of acidic gastric and duodenal contents into the distal esophagus. The major symptoms of GERD include heartburn, acid regurgitation, and non-cardiac chest pain. GERD is a common digestive disease with the direct medical costs estimated around $9.3 billion annually , and witMost of the factors involved in the pathogenesis of gastroesophageal reflux disease (GERD), previously described in European, Australian, and American studies, are present in Chinese patients with GERD, but at a lower scale. A low-fat diet probably contributes to a more favorable gastric distribution . AnotherIn general, the effects of diet on GERD are not well understood, and the currently available data in Western countries do not support a strong relationship between GERD and dietary fat, fiber, alcohol, and other nutrients. Although there are conflicting data regarding the role of dietary nutrients in GERD, there is no direct evidence that some nutrients promote or protect against GERD. Due to the difference in dietary nutrients between Chinese and Westerns, and few studies reporting the association between dietary nutrients and GERD in China, we employed food frequency questionnaire (FFQ) to evaluate the relationship between dietary components and RE in a Chinese population in the present study aiming to clarify whether the diet habits affect the prevalence of RE.A total of 537 Han Chinese were recruited from the Endoscopy Center of Tongji Hospital between May 2010 and May 2011 in Shanghai. Because the diet habits vary in different peoples and Han Chinese account for 91.51% of population in China, the Han Chinese were recruited in order to maximally ensure the accuracy of data. Among these subjects, the age of 268 patients who were newly diagnosed as RE based on the Los Angles (LA) classification ranged fThe whole protocol was approved by the Ethics Committee of Tongji Hospital. All subjects gave written informed consent before study. All subjects were trained to complete a detailed FFQ. Before survey, all subjects were required to complete a Reflux Diagnostic Questionnaire (RDQ), including \u201cany symptoms including heartburn, acid regurgitation, and noncardiac chest pain,\u201d and \u201coften changing dietary habits and avoiding certain foods.\u201d Controls with RDQ score of >12 were also excluded although the normal findings were present in the endoscopic examination. In order to avoid the influence of symptoms on the dietary intake, these subjects were asked to record the dietary intake before the onset of reflux symptoms. FFQ based on the Chinese Dietary Pagoda was adap2) was calculated as a ratio of weight (kg) to the square of height (m2). WC and HC were measured to the nearest 0.1\u2009cm and the mean of three measurements was obtained. Waist-hip ratio (WHR) was calculated as a ratio of WC (cm) to HC (cm).The height, weight, waist circumference (WC), and hip circumference (HC) were measured under fasting conditions followed by endoscopy. Height was measured to the nearest 0.5\u2009cm using a stadiometer, and weight to the nearest 0.25\u2009kg in light clothing and without shoes using standard digital scales. BMI were calculated on the basis of interquartile range for each nutrient and thus show risk comparing the 75th centile of intake for each nutrient with the 25th centile. A value of P < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS version 14.0 for Windows . All data were expressed as mean \u00b1 standard deviation (SD). P < 0.05). RE patients had a higher WC and WHR than controls (P < 0.05) and there were no differences in the height, weight, BMI, and HC (P > 0.05) between them. Data on nutrient and food intake obtained from the FFQ are shown in P < 0.05). The calories from protein (%), calcium, \u03b2-carotene, vitamin C, and vegetables were markedly lower in the RE group than in the control group (P < 0.05).The daily intake of total energy, protein, fat, carbohydrate, total SFA, dietary fiber, selenium, milk and dairy products, beans, and nuts was significantly higher in the RE group than in the control group (P > 0.05).There were no significant differences in the intake of calories from fats and carbohydrates (%), cholesterol, zinc, ferrum, vitamin E, grains and potatoes, fruits, meat, fish and shrimps, eggs, alcohol, oils, and salt , there was a positive dose-response relationship between RE and calcium , meat , oils , and salt , and there was an inverse dose-response relationship between RE and protein , carbohydrate , calories from protein (%) , vitamin C , grains and potatoes , fruits , and eggs .\u03b2-carotene, vegetables, fish and shrimps, milk and dairy products, soy, and nuts. The relationship between RE and different nutrients and food is shown in After adjustment for WC, WHR, total energy intake, and demographics , there was no correlation of RE with fat, total SFA, alcohol, cholesterol, calories from fat (%), calories from carbohydrate (%), dietary fiber, vitamin E, selenium, ferrum, zinc, This is the first study reporting an association between the risk for RE and dietary nutrients as well as food in a Chinese population. In this study, results showed that the RE was mild (Grade A and B) which was similar to previously reported , and RE Some studies have demonstrated that an increased prevalence of reflux symptoms in alcohol users, and alcohol is an independent risk factor for GERD-related symptoms, with alcohol consumption exacerbating GERD by increasing acid secretion through gastric stimulation, reducing LESP, increasing spontaneous LES relaxations, and impairing esophageal motility and gastric emptying , 40\u201342. Some previous studies found that an increase in salt consumption was associated with GERD , 45, whiSome experts proposed that high intake of vitamin C could exert a protective effect against GERD , 36. OurCalcium is an important nutrient related to many diseases. However, to date, no studies have confirmed the relationship between calcium and GERD. To our knowledge, this is the first study to reveal the relationship between calcium intake and RE after adjustment for confounding variables. Nevertheless, the mechanism of such relationship is unknown. We speculated that calcium may stimulate the gastric acid secretion , 50, whiThe incidence of GERD is on the rise in China due to high intake of meat, oils, salt, and calcium, while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for GERD, which is different from the findings in the study of El-Serag et al. The conflicting data may be attributed to differences in not only the race, geographic specificities, diet habit, and culture between Chinese and the Western, but the definition of GERD because studies based on GERD symptoms may be overinclusive, and our study based on GERD complications such as esophagitis is restrictive. Further studies are needed to clarify this association. Our study has some limitations: first, in the present study, incomplete data on vitamin and calcium supplements were not included for analysis, which may affect the determination of vitamin and calcium intakes; second, the folate, lutein, and other micronutrients were not employed for analysis and discussion since they are not included in Chinese Food Composition Tables; third, FFQ is not a particularly accurate dietary assessment tool, and there is potential for measurement error. However, FFQ is one of the most well validated and commonly used food frequency questionnaires; forth, the recall bias and residual confounding might also influence the results.Our results indicate that high intake of calcium, meat, oils, and salt is associated with an increased risk for RE while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for RE in Han Chinese. Further studies are required to explore the relationships among diet, obesity, and RE comprehensively."} +{"text": "Born Michelangelo Merisi, Caravaggio was later renamed after his hometown in northern Italy, a practice not unusual in his day. His father, an architect and majordomo to the Marquis of Caravaggio, died of the plague when the artist was still young, leaving him under the protection of the art-loving marquis. Like many children of his day, he learned early how to grind pigments for painting, and soon he was apprenticed to a good studio in Milan. At 21, he moved to Rome, anxious, if not fully qualified, to compete in the capital\u2019s bustling art world. This move to Rome began the tumultuous life journey of a man who changed the art of his day, had many followers (known as Caravaggists), and influenced future masters, from Rembrandt to Vel\u00e1zquez has disrupted the fruit\u2019s normal physiology, devitalizing the skin, allowing invasion of pathogens, and promoting decomposition.In our world, as in Caravaggio\u2019s, where light and darkness, beauty and horror, pleasure and danger are constantly at play, survival depends on keeping the elements of nature in balance, constantly tracking their course, monitoring their moves, and checking their excesses. Left untended and uncontrolled, nature\u2019s elements will thrive to unfair advantage, mutate to our detriment, and travel to our doorstep. In formerly out-of-the-way places like Mongolia, where control efforts have not always kept pace, old scourges maintain their insidious hold, a blemish on world health and a threat to balance and control."} +{"text": "The impact of donors, such as national government , private sector, and individual financial (philanthropic) contributions, on domestic health policies of developing nations has been the subject of scholarly discourse. Little is known, however, about the impact of global financial initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, on policies and health governance of countries receiving funding from such initiatives.This study employs a qualitative methodological design based on a single case study: Brazil. Analysis at national, inter-governmental and community levels is based on in-depth interviews with the Global Fund and the Brazilian Ministry of Health and civil societal activists. Primary research is complemented with information from printed media, reports, journal articles, and books, which were used to deepen our analysis while providing supporting evidence.Our analysis suggests that in Brazil, Global Fund financing has helped to positively transform health governance at three tiers of analysis: the national-level, inter-governmental-level, and community-level. At the national-level, Global Fund financing has helped to increased political attention and commitment to relatively neglected diseases, such as tuberculosis, while harmonizing intra-bureaucratic relationships; at the inter-governmental-level, Global Fund financing has motivated the National Tuberculosis Programme to strengthen its ties with state and municipal health departments, and non-governmental organisations (NGOs); while at the community-level, the Global Fund\u2019s financing of civil societal institutions has encouraged the emergence of new civic movements, participation, and the creation of new municipal participatory institutions designed to monitor the disbursement of funds for Global Fund grants.Global Fund financing can help deepen health governance at multiple levels. Future work will need to explore how the financing of civil society by the Global Fund and other donors influence policy agenda-setting and institutional innovations for increased civic participation in health governance and accountability to citizens. In recent years, a rise in the international financing of health programmes in developing nations have spurred scholars and policy-makers working on global health policy to undertake studies to better understand the effects of these initiatives -12. In pAn area that has also attracted interest but where empirical evidence is all but absent relates to the extent to which these external investments have enhanced local institutional capacity ,11,20. Ai.e., within and between agencies), inter-governmental , governmental-civil societal, and community-level processes and responses to disease: more specifically, government leadership, policy commitment, and agency cooperation , inter-governmental cooperation between national, state, and municipal health agencies . This was aided by the fact that the Adjunct Coordinator, Fabio Moherdaui, as well as the director of the NTP, Draurio Barreira, had previously worked in the National AIDS Programme and had extensive networks , experience, and a strong commitment to creating a collaborative partnership with the National AIDS Program .Coinciding with negotiations with the Global Fund to finalise contracts to receive funding, in 2005 the NTP created a special division, the F\u00f3rum Estadual das ONGs na luta contra a Tuberculose no Rio de Janeiro (Forum of State NGOs against Tuberculosis in Rio de Janeiro); S\u00e3o Paulo followed suit with the creation of its own F\u00f3rum that same year, as well as the Rede para o Controle Social da TB no Estado de S\u00e3o Paulo in 2005. These F\u00f3rums were comprised of community-based organizations, the church, businesses, sex worker organizations, feminist groups, as well as AIDS NGOs . This technical support also helps to increase PR accountability to the NTP . The NTP also regularly interacts with municipal health secretaries in Rio and other cities to ensure that it has adequate technical support . Because the NTP is accountable, through the CCM, to the Global Fund for the FAP and FIOTEC's performance, the programme has further incentives to work closely with these institutions and the municipalities in order to ensure policy success .Comit\u00eas Metropolitanos (Metropolitan Committees), which are independent entities, not financed by the Global Fund. Modeled after the 1988 constitutionally-mandated municipal health councils, these Comit\u00eas are public participatory institutions. AIDS NGOs, F\u00f3rum members, municipal health officials, people affected by TB, the church, and staff from the MOH\u2019s Global Fund supported programme periodically meet to closely monitor the provision of Global Fund financing, review all aspects of Global Fund programmes, grant performance, impact, discussions for creating new funding proposals and potential PRs, as well as networking . In order to ensure that the PR's work effectively, in 2006 members of civil society in Rio and S\u00e3o Paulo, in conjunction with municipal health secretariats and the NTP, created tworking ,65; D. BComit\u00eas have also emerged in eight other cities, namely Belo Horizonte, Fortaleza, Manaus, Porto Alegre, Recife, Salvador, S\u00e3o Lu\u00eds, and S\u00e3o Paulo. Because of the high incidence of the TB-HIV co-infection, S\u00e3o Paulo has created two Comit\u00eas, which are well known for exhibiting a very strong commitment to civic participation .Though initially created in Rio, Comit\u00eas have provided even further opportunity for the NTP to work closely with civil society and local health departments . The director of the NTP as well as MOH officials working on the Global Fund grant frequently attend Comit\u00eas meetings [ibid]; this demonstrates strong government support as well as oversight in the grant implementation process . Global Fund support has also provided new opportunities to deepen civic participation by directly involving TB victims and their supporters on the CCM. An analysis of recent budgetary allocations , it did not instigate national government interest and commitment to responding to TB. Rather, Global Fund financing complemented and further strengthened pre-existing efforts to address TB at the national government level .However, it is important to note that the Global Fund was limited in its direct contribution to the creation of multiple levels of health governance in Brazil. While the Global Fund did directly contribute to the creation of community-based accountability institutions as well as the PRs and Comit\u00eas implementing Global Fund policy. In addition, members of the Comit\u00eas in several cities were interviewed because of their experience working with the NTP and municipal health officials. Finally, those individuals not working in the TB sector were chosen for their knowledge of the TB sector, the NTP\u2019s interaction with the Global Fund, and personal impressions of the Global Fund\u2019s impact on health governance in Brazil. None of those interviewed for this study were chosen for their a-prior policy views and beliefs, thus allowing us to avoid the usage of biased interview data.With regards to NTP officials, the following individuals were interviewed: the director of the NTP, Draurio Barreira, October 20, 2009 and June 10, 2011 (30 minute phone interview); Patricia Werlang, NTP official, August 1, 2011 (email survey); a senior official within the NTP working on the Global Fund grant, November 5, 2009 (30 minute phone interview); and Fabio Moherdaui, NTP, June 16, 2006. With regards to municipal health officials, Vera Gallesi, coordinator of the S\u00e3o Paulo state TB program, October 13, 2009 (by phone); Margaret Dalcolmo, Reference Center for Tuberculosis, Rio de Janeiro, October 20, 2006; Germano Gerhardt, President, Funda\u00e7\u00e3o Ataulpho de Paiva, Rio de Janeiro, July 19, 2006; Bettina Dorovni, director of the division of AIDS, TB, and Colera, municipal department of health, Rio de Janeiro, July 7, 2006 (by phone).Members of civil society and activists included: Afranio Kritski, Universidade Federal do Rio de Janeiro, July 20, 2006; Carlos Basilia, director, F\u00f3rum Estadual das ONGs na Luta contra a Tuberculose no Rio de Janeiro, November 15, 2009 and October 17, 2006 (phone interview); Ezio T. Santos-Filho, Vice President, PellaVida NGO, Rio de Janeiro, June 30, 2006; members of the Global Fund Comit\u00eas Metropolitanos included: Nadja Faraone, S\u00e3o Paulo, June 4, 2010 (by phone); Joyce Matsudo, Manaus, Amazonia, August 17, 2010 (email survey); La\u00edze Brilhante, Rec\u00edfe, July 6, 2010 (email survey); Ana Cristina Alegria de Almeida, Costa da Mata Atlantica, S\u00e3o Paulo, July 1, 2010 (email survey).Those non-TB individuals that were interviewed included AIDS NGO leaders, activists, national AIDS officials and university professors: Veriano Terto, Executive Director of ABIA, Rio de Janeiro, May 22, 2012 (30 minute phone interview); Ezio T. Santos-Filho, former Vice President of PellaVida AIDS NGO, Rio de Janeiro, currently PhD Candidate, Medical School, Federal University of Rio de Janeiro, May 23, 2012 (30 minute phone interview); Ruy Borgos Filho, Director, National AIDS Program, Brasilia, May 23, 2012 (30 minute phone interview); and Mauro Sanchez, Adjunct Assistant Professor, University of Brasilia, Brasilia, July 2, 2011 (30 minute phone interview).The individuals interviewed for this study were chosen from officials working in the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the Brazilian National TB Programme (NTP), municipal tuberculosis officials, members of civil society participating in the The authors have no competing interests to declare.EG and RA are the primary authors of this study, having devised the theoretical and empirical analysis. All authors read and approved the final manuscript"} +{"text": "Stress is a major concern in medicine and the social and health sciences nowadays. In fact, not only are stress-associated ailments and diseases rapidly growing, that is, virtually everywhere in the modern world, but also the cost of treatment and \u201ccollateral damage,\u201d for example, in occupational health or the economy as a whole, seems to increase exponentially\u2014for example, see , 2. ThisSince primary care and health promotion can be seen as the first line of defense in medicine and, yet, as setting-oriented \u201cplaces\u201d where resistance resources, health protection, resiliency, and salutogenesis are facilitated in more complex situations and modalities, it should and will incorporate self-care-oriented means, techniques, and strategies to lower stress at all levels and improve self- or stress management skills of the population as a whole\u2014and of each single individual under treatment. Research in this area is evolving and it focuses on the many aspects that contribute to a healthy and more stress-resilient life-style, hence, looking not only at tangible disease outcomes but also at quality of life, happiness, flourishing, subjective well-being, optimism, and so on\u2014for example, see .With this special issue, we invited investigators to contribute original research as well as review articles that could stimulate the continuing efforts to understand the molecular, (patho)physiological, neurobiological, and, particularly, clinical factors that underlie stress and stress management programs or related interventions. Furthermore, we were interested in articles that focused on any mind-body medical, CAM, cognitive behavioral, or mindfulness-based technique that is believed or said to alleviate stress and the negative outcomes of its burden, that is, examining these interventions in clinical or out-patient and setting-oriented areas, including work-place, occupational and communal health, and, especially of interest, primary care.As expected, we received a broad array of papers and were able, following rigorous review procedures, to accept a couple of them that still cover the whole picture we had originally thought of. Papers on the effectiveness of a happiness training (positive psychology intervention) or on progressive muscle relaxation (PMR) during lunch breaks in the field of occupational health are now included, as are studies on the applicability and effectiveness of mind-body interventions and more complex programs, including mindfulness-based approaches or self-compassion training, in depression, in anxiety, or in general distress. Various settings are depicted, including the military or school and education. Finally, a focus lies on salutogenesis and resource-orientation in general practice.We hope this special issue meets the expectations of its readers, as it positively exceeded ours as editors. We are happy to herewith launch this special issue and open the discussion on the aspects raised.Tobias EschTobias EschGregory L. FricchioneGregory L. FricchioneStefanie JoosStefanie JoosMichael TeutMichael Teut"} +{"text": "Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, records of civil unrest of 170 countries during the period 1919\u20132008 are analyzed. It is demonstrated that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics. Civil unrest contagion occurs when social, economic, and political stress accumulate slowly, and is released spontaneously in the form of social unrest on short time scales to nearest and long-range neighboring regions that are susceptible to social, economic, and political stress A pertinent question from large-scale social dynamics and policymaking standpoints is what causes the extent and outbreaks of civil unrest spreading. Social unrest has been attributed to a variety of social, political, economic, and environmental causes including racial and ethnic tensions The model , and a characteristic urban cluster as defined by the U.S. Census Bureau (see the section Parameter Estimation for details). The outburst ions see .The unrest contagion model is sufficiently flexible to accommodate a wide range of possible unrest event count distributions. \u201cBroad-scale\u201d distributions that show a power\u2013law regime with a sharp cutoff in the tail are obtained when the infectiousness rate The unrest contagion patterns of each of the world\u2019s geographic regions are uniqThe reported results have several practical implications. First, the parameters of the model can be estimated from unrest data that includes small and medium sized events, and then be used to quantify the risk of large-sized events. Second, monitoring the parameters of the model and trends in their values over time through comprehensive ongoing unrest data, may serve as an early warning signal for increased vulnerability to social instability.This research utilizes a long-term dataset, which traces out several indicators of domestic conflict in 170 countries and covers the years from 1919 to 2008. These data are part of the comprehensive Cross National Time Series Dataset The countries and geographical regions included in this study are based on the United Nations geographical region classification Burundi, Comoros, Djibouti, Eritrea, Ethiopia, Kenya, Madagascar, Malawi, Mauritius.Mozambique, Rwanda, Seychelles, Somalia, Uganda, United Republic of Tanzania, Zambia, Zimbabwe.Middle Africa: Angola, Cameroon, Central African Republic, Chad, Congo, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Sao Tome and Principe.Botswana, Lesotho, Namibia, South Africa, Swaziland.Benin, Burkina Faso, Cape Verde, Cote d\u2019Ivoire, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, Togo.Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Afghanistan, Bangladesh, Bhutan, India, Iran (Islamic Republic of), Maldives, Nepal, Pakistan, Sri Lanka.China, Democratic People\u2019s Republic of Korea, Japan, Mongolia, Republic of Korea.Brunei Darussalam, Cambodia, Indonesia, Lao People\u2019s Democratic Republic, Malaysia, Myanmar, Philippines, Singapore, Thailand, Timor-Leste, Viet Nam.Armenia, Azerbaijan, Bahrain, Cyprus, Georgia, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syrian Arab Republic, Turkey, United Arab Emirates, Yemen.Belarus, Bulgaria, Czech Republic, Hungary, Poland, Republic of Moldova, Romania, Russian Federation, Slovakia, Ukraine.Denmark, Estonia, Finland, Iceland, Ireland, Latvia, Lithuania, Norway, Sweden, United Kingdom of Great Britain and Northern Ireland.Albania, Andorra, Bosnia and Herzegovina, Croatia, Greece, Italy, Malta, Montenegro, Portugal, San Marino, Serbia, Slovenia, Spain, The former Yugoslav Republic of Macedonia.Austria, Belgium, France, Germany, Liechtenstein, Luxembourg, Monaco, Netherlands, Switzerland.Antigua and Barbuda, Aruba, Bahamas, Barbados, Cuba, Dominica, Dominican Republic.Grenada, Haiti, Jamaica, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Trinidad and Tobago.Belize, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama.Argentina, Bolivia , Brazil, Chile, Colombia, Ecuador, Guyana Paraguay, Peru, Suriname, Uruguay, Venezuela (Bolivarian Republic of).Canada, United States of America.The output of the social unrest contagion simulation model is a set of unrest event counts. The goodness of fit of this set relative to the empirically observed unrest count distribution was determined by measuring the distance between the observed and simulated distributions. Here, the tail-weighted Kolmogorov\u2013Smirnov (wKS) statistic is used In this section the methods used to calibrate the social unrest contagion model shown in The social unrest contagion model is defined on a square grid of The spontaneous outburst The model was fitted to civil unrest data for each individual geographical region of the world using the tail-weighted Kolmogorov\u2013Smirnov (wKS) statistic as described in the section Assessing the Goodness of Fit of the Model. The model has two free parameters: the probability Social unrest diffusion is often transmitted by some sort of a communication network In this section, the effect of mass media distribution networks on the patterns of unrest activity is examined. Long-term population data, number of radio receivers, television receivers, and all telephones (including cellular) of all countries analyzed, covering the years from 1919 to 2008, are obtained As discussed in the section Telecommunication Technologies and Social Unrest, civil unrest may spread through media networks or through social networks where protesters contact their recruits in other cities, encouraging them to join a protest. In the section Model, this unrest spreading process was modeled by overlaying a small-world network on top of a two-dimensional grid. In this model, two kinds of links are considered: short-range links between sites that are directly adjacent to each other; and long-range links selected uniformly among all sites. While the short-range links capture the geographical nature of civil unrest spreading, a plausible alternative to the uniform distribution of long-range links would be to consider a more heterogeneous distribution. Here we are motivated by major advances that have been made in understanding the structure and dynamics of real-world social, biological, and technological complex networks Here, the role of fat-tailed distributions of long-range links in civil unrest spreading is analyzed. To this end, the small-world construction of the section Model is modified by replacing the uniform distribution of long-range links with a procedure in which the grid is augmented by a set of links randomly chosen from a power-law distribution. In particular, directed scale-free networks with different exponents were generated using the static model presented in We have tested the effect of various network topologies on civil unrest spreading. The computer simulations include: two-dimensional grids with a uniform distribution of long-range links as described in the section Model, and two-dimensional grids with a power law distribution of long-range links. For comparison, the scale-free networks were generated with roughly the same number of directed links as the uniform overlay networks (see"} +{"text": "Author Maria X. Sosa is missing from the author byline. Dr. Sosa should be listed as the fifth author and affiliated with institution number 1, Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetics Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Sosa should be noted as having made the following contributions to the article: Performed the experiments. The Citation should read: Sampath S, Bhat S, Gupta S, O\u2019Connor A, Sosa MX, et al. (2013) Defining the Contribution of CNTNAP2 to Autism Susceptibility. PLoS ONE 8(10): e77906. doi:10.1371/journal.pone.0077906.In addition, the first author, Srirangan Sampath, was incorrectly indicated as being the Corresponding Author of the article. The correct Corresponding Author is the last author, Aravinda Chakravarti. The last author's email address is already correct as indicated for the first author.In addition, the last author was incorrectly indicated as having changed affiliation to the institution now indicated as their Current Address, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America. This institution is the Current Address of the first author, not the last author."} +{"text": "AbstractJournal of the Bombay Natural History Society (JBNHS). The temporal scale of the dataset represents bird observations recorded between 1909 and 2007. The dataset has been developed by employing MS Excel. The key elements in the database are scientific name, taxonomic classification, temporal and geospatial details including geo-coordinate precision, data collector, basis of record and primary source of the data record. The temporal and geospatial quality of more than 50% of the data records has been enhanced retrospectively. Where possible, data records are annotated with geospatial coordinate precision to the nearest minute. This dataset is being constantly updated with the addition of new data records, and quality enhancement of documented occurrences. The dataset can be used in species distribution and niche modeling studies. It is planned to expand the scope of the dataset to collate bird species occurrences across the Indian peninsula.The northeast region of India is one of the world\u2019s most significant biodiversity hotspots. One of the richest bird areas in India, it is an important route for migratory birds and home to many endemic bird species. This paper describes a literature-based dataset of species occurrences of birds of northeast India. The occurrence records documented in the dataset are distributed across eleven states of India, viz.: Arunachal Pradesh, Assam, Bihar, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, Tripura, Uttar Pradesh and West Bengal. The geospatial scope of the dataset represents 24 to 29 degree North latitude and 78 to 94 degree East longitude, and it comprises over 2400 occurrence records. These records have been collated from scholarly literature published between1915 and 2008, especially from the The highest number of data records are from the family Muscicapidae (560 records), followed by Anatidae (180 records) and Accipitridae (136 records). The families with the least number of records are Hemiprocnidae, Podargidae, Indicatoridae with one data record each.Kingdom: AnimaliaPhylum: ChordataClass: AvesOrder: Podicipediformes, Pelecaniformes, Ciconiiformes, Anseriformes, Falconiformes, Galliformes, Gruiformes, Charadriiformes, Columbiformes, Psittaciformes, Cuculiformes, Strigiformes, Caprimulgiformes, Apodiformes, Trogoniformes, Coraciiformes, Piciformes, PasseriformesFamily: Podicipedidae, Phalacrocoracidae, Anhingidae, Ardeidae, Ciconiidae, Threskiornithidae, Anatidae, Accipitridae, Pandionidae, Falconidae, Phasianidae, Turnicidae, Gruidae, Rallidae, Otididae, Jacanidae, Rostratulidae, Charadriidae, Scolopacidae, Recurvirostridae, Glareolidae, Laridae, Rhynchopidae, Columbidae, Psittacidae, Cuculidae, Tytonidae, Strigidae, Podargidae, Caprimulgidae, Apodidae, Hemiprocnidae, Trogonidae, Alcedinidae, Meropidae, Coraciidae, Upupidae, Bucerotidae, Capitonidae, Indicatoridae, Picidae, Eurylaimidae, Pittidae, Alaudidae, Hirundinidae, Motacillidae, Campephagidae, Pycnonotidae, Irenidae, Laniidae, Troglodytidae, Prunellidae, Muscicapidae, Aegithalidae, Paridae, Sittidae, Certhiidae, Dicaeidae, Nectariniidae, Zosteropidae, Emberizidae, Fringillidae, Estrildidae, Passeridae, Sturnidae, Oriolidae, Dicruridae, Artamidae, Corvidae.General spatial coverage: This dataset collates species occurrences from northeast India and neighboring regions. The occurrence records collated in the dataset are Literature-based species occurrence data of birds of North-East India 3 distributed acrossPageBreak eleven provinces of India, viz.: Arunachal Pradesh, Assam, Bihar, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, Tripura, Uttar Pradesh and West Bengal. This region falls within the Himalayan mountain ranges, and spans an area of 234567 sq. km. The region borders with Bangladesh to the south, Bhutan to the west, Myanmar to the east and with China to the north. Minimum and maximum elevations are 2000 meters and 8000 meters above sea level respectively.Coordinates: 24\u00b030'0\"N - 28\u00b015'0\"N Latitude; 78\u00b022'58.8\"E - 93\u00b047'60\"E Longitude.1909\u20132007.Title: This dataset is an outcome of the collaborative work carried out by three projects, viz.:, (a) Environmental Information System (ENVIS) Centre on Avian Ecology, Bombay Natural History Society, sponsored by the Ministry of Environment and Forests, Government of India; (b) Important Bird Areas Programme and Indian Bird Conservation Network (IBA-IBCN), sponsored by the Royal Society for Protection of Birds, United Kingdom; and (c) Impact of Climate Change on the Conservation of Birds, a project supported by the MacArthur Foundation.Personnel: Sujit Narwade , Mohit Kalra (Processor), Divya Varier (Custodian Steward/Metadata Provider), Rajkumar Jagdish (Processor), Sagar Satpute \u00a0(Custodian Steward), Noor Khan (Custodian Steward), Gautam Talukdar (Publisher), V.B. Mathur (Publisher), Karthik Vasudevan (Publisher), Dinesh Singh Pundir (Publisher), Vishwas Chavan (Metadata Provider/Editor), Rajesh Sood (Metadata Provider/Programmer).Funding: Ministry of Environment and Forests, Government of India, (Funding), the Royal Society for Protection of Birds, United Kingdom (Funding), MacArthur Foundation (Funding), Bombay Natural History Society (Host institution), and Wildlife Institute of India (publishing support).Study area descriptions/descriptor: Northeast India is one of the most significant biodiversity hotspots of the world and among the richest bird zones in India. It is considered as the \u2018biological gateway\u2019 for much of India\u2019s fauna, as the Gondwana land first touched this region, during the Tertiary period. The north-eastern region is at the confluence of the Indo-Malayan, Indo-Chinese and Indian biogeographical realms. As a result, it is unique in providing a profusion of habitats that harbor diverse biota with a high degree of endemism Centre at the Bombay Natural History Society (BNHS) is a focal point for collection, collation PageBreakand dissemination of data on avian ecology in India. The objective of this dataset is to collate avian observations documented in various research publications such as journals, magazines, newsletters, project reports, theses, books and other gray literature. However, the current version of the dataset collates occurrence records reported in research articles published in the Journal of the Bombay Natural History Society (JBNHS). The motivation for this approach is because of the dispersed availability of the occurrence records in published literature. Because these data records are documented in several literature sources, it is difficult to access them together, inspite of being in the public domain. Thus, for a potential user it is not possible to access and use them when he/she needs them the most. Another consideration is the quality of these data records, as they are published in peer reviewed literature and their quality is expected to be \u2018fit for use\u2019. The data records were entered in a MS-Excel worksheet. The offline version of the dataset maintained by the Bombay Natural History Society is developed employing MS-Access. The key elements about which information is collated in the current version of the dataset includes: scientific name, common name, taxonomic classification, occurrence location, geo-coordinates, precision of geo-coordinates, date of observation, data collector, and primary source of the data record.The data records were entered in the MS-Excel worksheet. The offline version of the dataset maintained by the Bombay Natural History Society is developed employing the MS-Access. The key elements about which information is collated in the current version of the dataset includes, scientific name, common name, taxonomic classification, occurrence location, geo-coordinates, precision of geo-coordinates, date of observation, data collector, and primary source of the data record.Object name: Darwin Core Archive literature-based species occurrence data of birds of northeast IndiaCharacter encoding: UTF-8Format name: Darwin Core Archive formatFormat version: 1.0Distribution: http://ibif.gov.in:8080/ipt/archive.do?r=BNHS-NEWPublication date of data: 2011-06-30Language: EnglishLicenses of use: by-nc-saMetadata language: EnglishDate of metadata creation: 2011-06-30Hierarchy level: DatasetPageBreakWe are most thankful to the Ministry of Environment and Forests (MoEF), Government of India; the Royal Society for the Protection of Birds (RSPB), United Kingdom; and the MacArthur Foundation for financial support. We would like to express our deepest gratitude to Dr. Asad R. Rahmani, Director, BNHS and Principal Investigators of the aforementioned projects."} +{"text": "Clinical research indicates that negative calcium balance is associated with low bone mass, rapid bone loss, and high fracture rates. However, some studies revealed that not only calcium is involved in bone strengthening as risk factor of fracture osteoporosis. Thus, in this report, the difference of metallic and nonmetallic elements in osteoporosis and normal bones was studied by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). The influence of these elements on bone metabolic processes is also discussed. Inclusion criteria of bone samples consist of postmenopausal woman, trabecular bone fracture, normal and osteoporosis BMD value, and no history of previous disease. The results showed that the concentration of B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, and Ca/P ratio is higher in osteoporosis than normal. These atomic minerals have negative role to imbalance between bone resorption and bone formation activity. Conversely, concentrations of Na, Mg, P, K, Ca, Cr, Pd, Ag, Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se are lower in osteoporosis than in normal bones. Among these atoms, known to have important roles in bone structure, we found involvement of atomic mineral and calcium which are considerable to contribute to osteoporotic phenomena. Decreasing of skeletal strength and increasing of fragility and fracture risk was a marker of osteoporosis. This condition is caused by abnormalities of bone density and bone microstructure , 2. A feOrganic and inorganic components are responsible for toughness and rigidity of bone, respectively. Both of these substances also show the mechanical strength of the bone. Trabecular bone is more sensitive to hormones or other biological factors that are involved in modulating bone metabolism . Atomic iliac crest autopsy sample by atomic absorption spectrometry (AAS) and conclude that Zn, Rb, Se, Fe, Al, Cu, Pb are in mg/g level, and Ca is in g/mg level [Each atomic mineral was able to substitute another atomic mineral due its similarity in the atomic radius. Ren et al. showed that Zn substitution on hydroxyl apatite crystal was found to inhibit crystal growth due to its smaller atomic radius as compared with Ca . This fimg level . Brodziamg level . Zaichicmg level . Alfv\u00e9n mg level . HoweverSo far, no detail information is dealing with the bone quality of Indonesian people. We just believe that its quality is not solely determined by calcium, but no explanation as an answer of the hypothesis of why in Indonesian population the fracture rate of osteoporosis are low does not in accordance with the fact of low Calcium intake. Accordingly, the objective of this study is to investigate the characteristics of atomic mineral in Indonesian osteoporosis and normal bone by HR-ICP-MS. About 27 elements were successfully analyzed, which include B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, Na, Mg, P, K, Ca, Cr, Pd, Ag, Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se. The present study provides more detail information of atomic mineral compositions as well as better understanding for the association of atomic mineral with osteoporosis.3 and 1\u2009mL of H2O2 were added. The temperature program of a microwave irradiation was ramped to 220\u00b0C within 15\u2009min and kept at this temperature for 10\u2009min. After cooling the vessels, proper amounts of the internal standard solution contained Rh and Re were added. Then, all solutions in the vessels were transferred into polypropylene bottles and diluted with 0.1\u2009M HNO3 up to 50\u2009mL. Minimal samples for normal and osteoporosis groups based on Epi Info version 6 were 32 samples for both groups. Statistical analysis was performed using t student-test, and P\u2009\u2009value < 0.05 was considered statistically significant.The study was mainly conducted in the Department of Orthopaedics, Ulin General Hospital of Banjarmasin and the Department of Orthopaedics, Syaiful Anwar Hospital of Malang from September 2010 to January 2011. Inclusion criteria consist of postmenopausal woman, trabecular bone fracture, normal and osteoporosis BMD value, age less than 50 years, and no history of previous disease. Bone was obtained in surgery room and then analysed for its atomic mineral compositions using HR-ICP-MS at the Division of Nanomaterial Sciences, EcoTopia Science Institute, Nagoya University, Japan. The mineral measured consists of 27 elements, such as B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, Na, Mg, P, K, Ca, Cr, Pd, Ag, Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se. Prior to ICP-MS measurement, dry weight of bone samples were digested with a microwave-assisted acid digestion system . Approximately 100\u2009mg of the sample in a PTFE digestion vessel was weighted, into which 4\u2009mL of HNOFifteen osteoporosis BMD and twenty three normal BMD values were involved in this study. HR-ICP MS analytical results showed different concentration of atomic minerals in osteoporosis and normal postmenopausal women. The concentration of B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, and Ca/P ratio in osteoporosis bones was found higher than that of normal bone as shown in Geometrics pattern of bone atomic minerals for substitution or incorporation is based on the properties of atoms in the periodic tables of Mendeleev. Substitution is the replacement of an atom with other atoms due to the similarity of atomic radius and atomic charge. Incorporation is joining an atom to a molecule and/or a composite that can alter the integrity of a molecule. Molecular cavity can also play considerable role in substitution or incorporation of atoms. All of these phenomenons significantly affect the properties and structure of bone crystal.P < 0.05) in osteoporosis bone than in normal bone. Concentration of Pd, Rb, and, Se is higher significantly (P < 0.05) in normal bone than osteoporosis bone.The concentration of B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, and Ca/P ratio in osteoporosis is higher than in normal bone. These atomic minerals have negative role in imbalance between bone resorption and bone formation activity. Conversely, the concentration of Na, Mg, P, K, Ca, Cr, Pd, Ag, Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se in osteoporosis is lower than in normal. Beside that, concentration of B and As is higher significantly (P < 0.05) and indicates decrease in a bone mineral density. Since boron is substitution mineral for phosphorus, the concentration level of phosphorus in osteoporosis bone would be lower than in normal bone as observed in this study. Simulation using crystal maker software shows that the substitution of phosphorus by boron resulted in decreasing atomic density for both osteoporosis and normal hydroxyapatite bones as shown in As it is well known, plant is a rich source of boron, but meat and fish are poor sources of boron . Effect \u0160\u010dan\u010dar et al. reported that concentration of aluminum in bone from autopsy subject was 3\u201310\u2009mg/kg . Effect Vanadium, nickel, cobalt, and arsenic are toxic metals for osteoblast in vitro. High concentration of these metals induces osteoblast apoptosis \u201322. In tThe highest concentrations of Barium in the body are found in the bone, and it is primarily deposited in areas of active bone growth . The uptIron has a role in bone formation as an enzymatic cofactor for the synthesis of collagen. Calcium could inhibit the iron formation. Beside that, iron is also toxic for bone cell, which can induce osteoporosis by disturbing bone mineralization , 25. \u0160\u010da\u0160\u010dan\u010dar et al. also found that concentration of copper in bone from autopsy subject was 100\u2013200\u2009mg/kg . Copper Magnesium was not a main component in hydoxyapatite crystal but was able to join with this crystal. Magnesium is substitution mineral for calcium in composite hydroxyapatite crystal . MagnesiManganese was prominent atomic for mucopolysaccharide metabolism that affects the organic matrix formation. Manganese was able to substitute calcium due to similar oxidation state. In osteoporosis patient, manganese was found in low level , 24. ProZinc has been demonstrated to be an essential element for normal growth of skeleton and bone metabolism. The concentration of zinc in bone is higher than in the other tissues . Zinc is\u0160\u010dan\u010dar et al. found that concentration of strontium in bone from autopsy subject was 13\u201360\u2009mg/kg . AccordiLead in organic or inorganic forms is absorbed through the lungs and gastrointestinal absorption. Organic leads also absorbed through a skin. Inhalation exposure was more common in occupational setting, whereas in the general population through the ingestion route , 41. Up Selenium was a mineral found in soil and organism. Selenium was incorporated into protein as selenocysteine. Selenoprotein was important for bone metabolism. The population with selenium deficiency was found higher in osteoporosis incidence . In thisPalladium, silver, and lantanadium are atomic minerals for unknown function that need further investigation.In summary, among these atoms, known to have important roles in bone structure, we found involvement of atomic mineral and calcium which are considerable to contribute to osteoporotic phenomena. These mineral atomics would determine bone mass density. To our knowledge, this study is the first time to provide such evidence. Consideration of involvement of mineral atomic beside calcium in osteoporosis is warranted to prevent osteoporosis."} +{"text": "Campylobacter, Escherichia coli O157:H7, Enterococcus, non-Typhi Salmonella, Salmonella Typhi, and Shigella.National Antibiotic Resistance Monitoring System (NARMS)\u2013enteric bacteria is a collaboration by the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration, the Center for Veterinary Medicine (FDA-CVM), and the U.S. Department of Agriculture, Agricultural Research Services (USDA-ARS). NARMS was established in 1996 and monitors antimicrobial drug resistance in The 2004 meeting was held March 4\u20135 in Decatur, Georgia, and hosted by the Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC. The meeting highlighted data from scientific studies and surveillance for antimicrobial drug resistance in the United States and abroad with enteric bacteria isolated from humans, animals, and retail foods. Approximately 180 participants from 14 countries, representing 71 organizations, attended the meeting. The organizations included international and national public health agencies, state and local health departments, public health laboratories, industry consumer groups, and academic institutions from Australia, Canada, Cameroon, China, Denmark, Europe, Italy, Japan, Philippines, Poland, Thailand, the United Kingdom, the United States, and Vietnam.The meeting began with a World Health Organization expert's summarization of a recent workshop on nonhuman antimicrobial drug use and antimicrobial drug resistance. Scientific assessment and risk management of antimicrobial drug use in agriculture and human and veterinary medicine were examined. A plenary session on the human health consequences of antimicrobial drug resistance consisted of two presentations from the United States and two presentations from Denmark.Salmonella infection, as compared to susceptible ones, were presented. The results of another CDC study that found higher frequencies of bloodstream infection and hospitalization with resistant Salmonella infections, as compared to susceptible ones, were presented. A presentation from the Statens Serum Institut in Denmark highlighted the association between flouroquinolone-resistant Campylobacter infections, as compared to susceptible ones, and a higher frequency of invasive illness, hospitalization, and death. A second presentation demonstrated increased death rates in resistant S. Typhimurium infections, as compared to susceptible ones. Other speakers highlighted emerging resistance to clinically important antimicrobial drugs, environmental studies on antimicrobial drug resistance, antimicrobial drug resistance in commensal bacteria, partner perspectives on antimicrobial drug resistance, international perspectives on antimicrobial drug resistance, and NARMS educational activities. A presentation of the \"GET SMART: Know When Antibiotics Work on the Farm\" campaign highlighted educational efforts to promote the appropriate use of antibiotics in veterinary medicine. The campaign currently includes an interactive Web-based program on aspects of microbiology, pharmacology, infectious disease, and public health for veterinary students and veterinarians who participate in continuing education programs. The conference also included brief summaries of three recent outbreaks of multidrug- resistant S. Typhimurium DT104 R-type, which has become a common strain of Salmonella isolated from humans and was resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracyclines. More information about NARMS and antimicrobial resistance can be found at www.cdc.gov/NARMS.The results of a study conducted by CDC that found higher rates of hospitalization and death in resistant"} +{"text": "There are three NOS-isoforms, NOS1-3, which have been originally termed neuronal, inducible and endothelial NOS, respectively Wang, . Recentl2S have still not been sufficiently determined. The measurement of endogenous gas concentrations is limited by the accuracy and specificity of currently available methods (Olson, 2S (Kimura, Despite the knowledge of the substrates and specific enzymes which are involved in gasotransmitter production, the precise endogenous concentrations of NO, CO, and Hs Olson, , the reas Olson, , and sim Kimura, .Although precise endogenous concentrations of gasotransmitters remain to be determined, numerous studies investigated the physiological effects of those gaseous signaling molecules in almost every organ system [as summarized in excellent review articles such as Olson , Wu and 2S. Excellent review and research articles highlight the importance of gasotransmitter/ion channel interactions for vegetative physiology (Althaus, This research topic summarizes currently available data on the regulation of ion channels and transporters by NO, CO, and HAlthaus, , neurophAlthaus, , and expAlthaus, . FurtherAlthaus, give per"} +{"text": "Human population has increased from 3,031,092,442 in 1960 to 6,879,100,100 as on date. The highest populated country of the world is China (19.5%) followed by India (17.3%). Population genetic frequencies are ethnically based on the religion, country, region and community that are studied. Some of the major ethnic groups as per the region of the world are American Indians, Australoid Aboriginals, Caucasoid, Hispanics, Orientals, Blacks, Pacific Islanders, Iranians, Negroids, Persians, Russians, Jews etc., depending on the continents such as Africa, America, Asia, Australia. Many religious linguistic groups in each part of the world have evolved during earth\u2019s time course as rightly pointed out in 1973[India, with 1,189,700,000 people, having 3824 castes and 461 tribes and many unique languages families, is one of the megadiversity countries and the largest democracy in the world. It is the second continent to have been occupied by man since the past 60,000 years. Many early migrations settled in various parts of the world especially Central Asia, Eurasia, Middle East, Pakistan and India when huge expansions of human occurred. As a result, almost all forms of religious and social events like marriage and family styles have been experimented. The basic pattern of the society and value system seems to have been laid down well before the origin and spread of Dravidian and other languages in India. While India was an ancient land of immigration spread of very many streams of people, Africa was a land of origin, expansion and divergence of the same gene pool for the past 0.2 million years.A caste or tribe is a breeding unit and a breeding isolate: as time passes they drift away from one another. A tribe in most of the instances are primitive in their mode of subsistence, economy and living conditions, mostly living in isolation in hilly terrains sight of the modern developments. Castes on the contrary live in plains and are capable of articulation and egging their income in more modern interdependent societies, villages and township. Most of these castes and tribes in India are inbred and endogamous, though the degree varies from one region to other. Each caste/tribe is made of many clans, mostly patriliny, though matriliny is the ancient form of lifestyle and is practised even today in many tribes of India. Each caste/tribe is a social unit and a social security system defined by their own characteristics, territory, space, job and interdependency. Different castes living in the same region, sharing the environment and epidemiology as on date are sympatrically isolated in terms of their gene pool. This has great significance in terms of epidemiology and infectious disease transmission and susceptibility. It is known that not all the infected develop the disease.People having two different genetic make up may not be equally susceptible to a given disease, though the nature\u2013nurture interaction plays a dominant role in the incidence and prevalence of various diseases. Theoretically, high polymorphism of HLA gene can occur due to mutation rate, selection, genetic hitchhiking or a combination of all the three. Indigenous populations or caste/tribal groups show a very restricted diversity of alleles at a particular HLA locus consistent within a population. Studies on HLA allelic diversity of among 838 population groups from Asia 272), Western Europe 147), South and Central America (107), North America 79), Pacific 59), sub-Saharan Africa (55), Eastern Europe 56), Middle East (34), North Africa (21) and Australia (8) of the world have revealed that some common alleles such as HLA A*02 (20\u201328%), B*40 (5\u201320%), and DRB1*15 (10\u201318%) are seen in Asian countries such as Afghanistan, Armenia, Azerbaijan, Bahrain, Bangladesh, Bhutan, Brunei Darussalam, Cambodia, China, East Timor, Georgia, India, Indonesia, Iran, Iraq, Israel, Japan, Jordan, Kazakhstan, Lebanon, Malaysia, Maldives, Middle East, Mongolia, Myanmar, Nepal, North Korea, Oman, Pakistan, Philippines, Qatar, Saudi Arabia, Singapore, South Korea, Srilanka, Syria, Taiwan, Tajikistan, Thailand, Turkmenistan, UAE, Uzbekistan, Vietnam and Yemen.[7, South 9, sub-Sa, Middle 2, Wester, Pacific"} +{"text": "Preventing Chronic Disease: Public Health Research, Practice, and Policy (PCD). In our introductory editorial, we defined our primary audience as researchers in chronic disease prevention and intervention and health practitioners responsible for reducing the effects of chronic conditions and improving population health on the US\u2013Mexico border in Arizona. Today, most PCD articles include Spanish translations.We also wanted PCD evolved? A perusal of journal content between December 2011 and July 2012 finds articles on not only subjects of ongoing public health interest such as social determinants, nutrition, breast health, diabetes, and surveillance but also topics such as health financing, veterans\u2019 health, and health informatics. International health is represented by reports from Mexico, Australia, Canada, Jordan, Ethiopia, and Grenada.In that 10-year blink, how has PCD is now published continually, provides new media opportunities , and offers continuing medical education credits. The number, breadth, and quality of the articles have increased. The journal supports an annual student paper competition and provides podcasts of selected authors discussing their work. In addition, the journal has added a fourth goal to the original 3: encouraging multisectoral partnerships that engage communities (munities .PCD to date: gestation, birth, infancy, childhood, and adolescence. The journal is well positioned to move on to young adulthood and maturity. Happily, a journal need not experience senescence or death, and we can look for increasing quality, influence, and readership in the future.Ten years are a lifetime. The classic life-cycle metaphor can be used to describe the growth and development of Ten years ago, my first editorial spoke of chronic diseases in my parents\u2019 generation. Today, all of that generation of my family is gone, and among my own generation others have been lost to chronic diseases. Let us hope our work will enhance the health of our children \u2014 they, too, have a lifetime, and we will be gone in a blink."} +{"text": "Asthma affects more than 22 million persons in the United States, including more than 6 million children. In the past 2 decades, the gap between science and clinical practice has been narrowed by better understanding of asthma pathophysiology and improvements in therapeutic approaches, which have been well described in national and international management guidelines.,2 Noneth\u03b2-agonists for symptom control. The second is risk, defined as the propensity for exacerbations, treatment-related side effects, and progressive loss of lung function over a period of time. Although impairment can be quantified effectively and is well addressed by current treatment approaches, the same cannot be said for risk. However, risk will have a more profound effect on patients' disease over time.Current guidelines call for treatment decisions to be based on assessments of disease severity.,2 These There are differences among the major asthma guidelines, and whether the differences can be (or need to be) reconciled is not yet clear. If so, the next question is whether guidelines should be universal and standardized internationally.These questions were the focus of interesting, and sometimes controversial, dialogue at the inaugural Asthma Summit held in Baltimore, MD, in February, 2009. International key opinion leaders, physicians, and scientists convened to discuss state-of-the-art issues in asthma genetics, pharmacotherapeutics, and clinical management. Entitled, Beyond the Guidelines, the Summit explored how to \"operationalize\" the concepts of asthma control, dosing flexibility, and heterogeneity of disease to help clinicians improve patient care.Chaired by William Busse, MD, a distinguished faculty of international prestige, including Jean Bousquet, MD; Chris Brightling, MD; William Calhoun, MD; G. Walter Canonica, MD; Gene Colice, MD; Frederick Hargreave, MD; Erwin Gelfand, MD; and Stephen Lazarus, MD, presented the most current clinical aspects of their research. The research presentations were followed by interactive panels, workshops, and debates with the goal of applying the findings to everyday patient issues. The program was developed by a steering committee that included Bradley Chipps, MD; Peter Dicpinigaitis, MD; Michael Kaliner, MD; Allan Luskin, MD; Sheldon Spector, MD; and William Storms, MD.It is evident that many patients with asthma want to reduce their medications, but whether treatment can be flexible has been a matter of debate. In addition, new treatment approaches, such as those that address early life events, multiphase aspects of inflammation, or allergic factors, have not been explored fully. Consideration of these questions and further improvement of asthma management will require a view of asthma not as a single disease, but as one with many ramifications and end points. Furthermore, although guidelines provide direction on how to treat patients with asthma, it is likely that treatments will have to become more patient specific. These are some of the issues discussed by faculty and attendees at the Asthma Summit, which are captured in the following articles and discussion.These Proceedings are sponsored by LifeSciences Press, LLC, and supported by an unrestricted educational grant from Sepracor, Inc.All content has been derived from the Asthma Summit 2009, which was sponsored by SRxA Institute for Professional Education and Medical Education Resources and funded by unrestricted educational grants from Sepracor, Inc.; Abbot Laboratories; Graceway Pharmaceuticals; Strategic BioSciences; and the TREAT Foundation."} +{"text": "Tim Gilberger should be included in the list of participants in the malERA Young Investigators/Basic science meeting 8-9 October 2009, Boston, Massachusetts, USA. He is affiliated with the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany."} +{"text": "Although the importance of controlling postprandial glycaemia (PPG) was recognised in the position statement, they expressed the view that the GI could be \u2018misleading\u2019 and \u2018would not add value\u2019 to the existing standards for nutrition labels. Unfortunately, several statements indicate a lack of understanding of the evidence base for current information on food labels and of the GI concept in particular.On behalf of Health Canada, Aziz . Ideally, plasma glucose levels at the 2\u00a0h time point after a meal should be <\u00a07\u00b78\u00a0mmol/l since values above this level are considered to indicate the presence of impaired glucose tolerance (IGT), which may be indicative of pre-diabetes, a condition which is more prevalent than diabetes itself. Both type 2 diabetes mellitus and IGT are increasing at an alarming rate, largely due to obesity and sedentary lifestyles. Mitigating the risk of adverse outcomes associated with elevated PPG is an important target for population health.The clinical relevance of PPG is now recognised by health institutions worldwide,3. Iet al. concluded that the GI was not useful because: (1) it has poor accuracy and precision for labelling purposes, (2) it does not vary in response to the amount of food consumed and (3) it is not congruent with national nutritional policies and guidelines.For food labelling purposes, the challenge is to find the best tool for evaluating a product's impact on PPG within the context of other health recommendations. Although the GI has a long history of use in research and clinical practice, Aziz as a method to assess the glycaemic impact of available carbohydrates. The GI value of one food is calculated from 640 data points . The margin of error of <\u00a015\u00a0% (i.e. the standard error of the mean expressed as a percentage of the mean) is considered reliable in the context of the considerable day-to-day variation in glucose tolerance in healthy individuals (\u00a0\u00b1\u00a030\u201350\u00a0%). By testing a reference food, the GI method takes into account \u2018between-person variation\u2019.To address the first issue, the GI methodology is recognised and described by the International Standards Organization (26\u00a0642:2010) and by the Food and Agriculture Organization of the United Nations4 as aConcerning the accuracy and precision of any nutritional attribute, one cannot let perfect be the enemy of good. For example, both whole-grain and fibre claims are permitted on food labels, despite the fact that the definition and measurement of each varies among nations and is neither perfect nor precise. A whole-grain product may contain only 50\u00a0% whole grains according to the Food and Drug Administration, and there is marked disagreement of what fibre is and how it should be measured. Moreover, total carbohydrates on food labels are often described as \u2018carbohydrate by difference\u2019, which is calculated by subtracting the sum of the water, protein, fat, dietary fibre, ash and alcohol contents from 100. This method compounds the errors associated with all assays and often differs markedly from the direct measurement of the available carbohydrate. In addition, there is a permitted margin of error of <\u00a020\u00a0% for any component listed in the nutrition panel, which is considerably higher than the margin of error considered reliable for the GI of a food (\u00a0<\u00a015\u00a0%). In this context, the GI is being held to a much higher standard than other nutritional attributes.et al. was that the GI does not vary in response to the amount of food consumed. Informed consumers would anticipate that the greater the amount of the available carbohydrate consumed, the greater the increase in blood glucose. The key value of the GI therefore is that it allows comparisons between foods on a gram-for-gram carbohydrate basis, which is important for consumer choice. The glycaemic load (GL) per serving (the product of the available carbohydrate content\u00a0\u00d7\u00a0GI) varies in response to the amount consumed, and could be included in the nutrient panel together with the GI.The second issue identified by Aziz . However, this concern relates to any dietary claim, including \u2018low fat\u2019 and \u2018high fibre\u2019. Of note, Health Canada's concern is inconsistent with their earlier statement that \u2018low-GI diets have attributes of generally recognized healthy eating patterns\u2019. However, to address their concern that the composition of a low-GI food may not always be congruent with nutritional guidelines, our suggestion would be to consider a GI claim in conjunction with a healthy food profile. Programmes such as the GI symbol in Australia require the fulfilment of strict nutritional criteria that are consistent with dietary guidelines in order for a food to be eligible to use the certified GI logo.With respect to the third issue, Health Canada claims that the GI is not congruent with national nutritional policies and guidelines, implying that the GI would be used in isolation, irrespective of other important attributes such as saturated fat, fibre and whole grain content. We agree that the GI should not override sound dietary advice1. Howet al. that \u2018consumers are familiar with the concept, even though their understanding of it might not be accurate\u2019. In our view, this largely reflects the lack of communication about the GI to the general public and health professionals. The assumption that the GI concept may be too difficult for the lay person is not supported by the Australian experience, where surveys indicate that one in four Australians look for healthy low-GI foods when shopping, simply substituting healthy low-GI varieties for regular high-GI variants within a food group/category. Moreover, low-GI dietary advice in randomised clinical trials is associated with high completion rates (low attrition), suggesting that simple low-GI communications can be effective. As in the case of quality of fat , health agency advice preceded information now commonly listed in the nutritional panel.We agree with Aziz et al. proposed that nutritional recommendations should take a food-based approach. We agree, yet Health Canada's recommendation to increase intakes of whole foods in the form of vegetables, fruits, grains and pulses does not address the main carbohydrate sources of most populations, i.e. breads, breakfast cereals, rice and ready-to-eat cereal products. Pasta, a staple carbohydrate food of the heart-healthy Mediterranean diet, is a refined yet low-GI carbohydrate food. Most basmati and parboiled rice are white yet have a low GI. There is also a need to distinguish high-GI from low-GI whole grains. Indeed, advice to \u2018choose more intact, unprocessed or minimally processed whole-grain products instead of their highly processed counterparts\u2019 is aimed at lowering overall dietary GI or GL. It is a common myth that all whole-grain products have low-GI values when in fact many are highly processed and correspondingly easy to digest. In clinical trials, low-GI diets have produced superior outcomes compared with the high-fibre\u2013high-GI diets. We suggest that GI labels may in fact stimulate the food industry to produce genuinely healthier whole-grain products that retain the low GI of the original grain.Finally, in their conclusions, Aziz and cardiovascular disease in large prospective cohort studies of diverse populations. Similarly, randomised controlled trials have shown the benefits of low-GI diets for weight management, serum lipids, insulin sensitivity and inflammatory markers. Most importantly, the selection of low-GI foods has resulted in the successful improvements of glycaemic control, dyslipidaemia and inflammation in people with type 2 diabetes. In this regard, these lines of evidence have been used to support the inclusion of low-GI and low-GL dietary patterns in the evidence-based nutrition recommendations of the Canadian Diabetes Association, American Diabetes Association, Diabetes UK, Diabetes Australia, International Diabetes Federation and the European Association for the Study of Diabetes. If GI values were not precise, one would not expect to see distinct differences in PPG in response to low- or high-GI meals observed at different time points throughout the day. These beneficial outcomes would not be possible if the GI concept were unduly undermined by large variability or differences among people of different ethnicity.Finally, if GI values are misleading and unreliable as Health Canada claims, then it is truly remarkable that a lower dietary GI/GL has been independently associated with a reduced risk of type 2 diabetes13 andTaken together, Health Canada's evaluation misinterprets and misrepresents current scientific evidence, in part by taking the GI outside the context of a healthy diet. In view of the proven health benefits of low-GI diets \u2018as currently defined and measured\u2019, every effort should be made to assist consumers in choosing carbohydrate foods that will not exacerbate PPG.International Carbohydrate Quality Consortium (ICQC)David J. A. Jenkins (ICQC chair), Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, Ontario, Canada.Walter C. Willett (ICQC chair), Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.Arne Astrup, Department of Nutrition, Exercise and Sports (NEXS), Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Livia S. A. Augustin, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, Ontario, Canada.Sara Baer-Sinnott, Oldways, Boston, MA, USA.Alan W. Barclay, Australian Diabetes Council, Glycemic Index Foundation, Sydney, Australia.Inger Bj\u00f6rck, Antidiabetic Food Centre, Lund University, Lund, Sweden.Jennie C. Brand-Miller, Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, Australia.Furio Brighenti, Department of Food Science, University of Parma, Parma, Italy.Anette E. Buyken, Department of Nutritional Epidemiology, University of Bonn, Bonn, Germany.Antonio Ceriello, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.Cyril W. C. Kendall, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.Carlo La Vecchia, Department of Epidemiology, Mario Negri Institute, and Professor of Epidemiology, University of Milan, Milan, Italy.Geoffrey Livesey, Independent Nutrition Logic, Wymondham, UK.Simin Liu, Department of Epidemiology and Medicine, Brown University, Providence, RI, USA.Andrea Poli, Nutrition Foundation of Italy, Milan, Italy.Gabriele Riccardi, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.Salwa W. Rizkalla, National Institute of Health and Medical Research (INSERM), ICAN Institute of Cardiometabolism & Nutrition, University Pierre et Marie Curie \u2013 Paris 6, Centre of Research in Human Nutrition, Piti\u00e9 Salp\u00eatri\u00e8re Hospital, Paris, France.John L. Sievenpiper, Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, Ontario, Canada; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.Antonia Trichopoulou, World Health Organization Collaborating Centre for Food & Nutrition, Department of Hygiene and Epidemiology, University of Athens Medical School, Hellenic Health Foundation, Athens, Greece.Thomas M. S. Wolever, Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada."} +{"text": "There was an error in the Author Contributions. CFJA, PM, ND, CSW, DJR and MJD wrote the paper."} +{"text": "The Funding statement was incorrect. The correct version is:This work was supported by grants from the Crafoord Foundation, VELUX stiftung, Clas Groschinskys Foundation, Kronprinsessan Margaretas Arbetsn\u00e4mnd f\u00f6r synskadade (KMA), Karin Sandqvist Foundation, Maggie Stephens Foundation, Magnus Bergvall Foundation, Per Westling Foundation, and the Nanometer Consortium at Lund University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."} +{"text": "A commentary onThe danger theory: 20 years laterby Pradeu, T., and Cooper, E. L. (2012). Front. Immunol. 3:287. doi: 10.3389/fimmu.2012.00287The \u201cdanger theory\u201d of Polly Matzinger posed in 1994 (Matzinger, Recently, the danger theory was emphasized in this journal by Pradeu and Cooper who assessed the topic in view of recently published experimental data (Pradeu and Cooper, The injury hypothesis\u2014which equals the danger theory\u2014is based on stringent observations from a clinical trial in kidney transplant patients that was conducted during the late 1980s/early1990s, that is, even more than 20 years ago. Basically, the clinical data obtained from this trial showed that mitigation of postischemic allograft reperfusion injury by intraoperative injection of a single dose of the oxygen free radical scavenger \u201csuperoxide dismutase\u201d results in a statistically significant reduction in incidence of both acute and chronic rejection events (Land et al., Walter Land, ex-head of experimental surgery at the Medical School, Munich, Germany was one of the first surgeons to understand the danger model. In a way, he discovered it before I published it\u201d (Matzinger, In fact, as recently pointed out by Matzinger (Matzinger, innate immunity. Interestingly enough, that happened before the groups of the Nobel Laureates Jules Hoffmann (Lemaitre et al., In the same article published by us in 1994 (Land et al., Innate Alloimmunity (Land, DAMPs in the sense of damage-associated molecular patterns a year later (Land, During subsequent years, the injury hypothesis was extended and modified several times Land, ,b, 2005.ty Land, followeder Land, . Of noteer Land, , 2005.In more recently published review articles, we have updated the concept of allograft injury-induced innate alloimmunity Land, ,b,c. In Finally, the whole concept of the injury hypothesis, in light of the international literature on innate immunity currently available, has been thoroughly and comprehensively discussed in a monograph that was published as two parts in 2011 Land, ,b.Frontiers in Immunology with this information about the history of both, the danger theory and the injury hypothesis as related to organ transplantation; a note that may serve as a useful addendum to the excellent article of Pradeu and Cooper.We thought it would be worthwhile to provide the reader of"} +{"text": "We, as organizers and participants of the 2011 Growing Older with a Disability (GOWD) Conference, a part of the Festival of International Conferences on Caregiving, Disability, Aging and Technology (FICCDAT), held in Toronto, Canada June 5\u20138, 2011 forward this declaration and invite governmental, non-governmental, professional, and consumer stakeholders to join us in supporting and implementing this plan of action.The 2011 World Report on disability, produced jointly by the World Health Organization (WHO) and the World Bank, estimates that there are over one billion people with disabilities in the world today, of whom nearly 200 million experience significant difficulties. At the same time, in almost every country, the proportion of people aged over 60 years is growing faster than any other age group, forecast to reach 1.5 billion by 2050, according to the Global Health and Aging Report, also released in 2011 by WHO in partnership with US National Institute on Aging. This means that in the years ahead disability will be an even greater concern to developed and developing nations due to aging populations, higher risk of disability in older people, as well as the global increase in chronic health conditions, such as diabetes, cardiovascular disease, cancer and mental health disorders. Taken together, the dual phenomena of global aging and increased longevity for individuals with disabilities represent significant advances in public health and education.However, along with these positive trends come new challenges for the 21st century. These include: strains on pension and social security systems; preparing health providers and societies to meet the needs of populations aging with and aging into disability; preventing and managing age and disability associated secondary conditions and chronic diseases; designing sustainable policies to support healthy aging and community-living as well as long-term and palliative care; and developing disability and age-friendly services and settings.Bridging the fields of aging and disability research, policy, and practice is critical for meeting these challenges. All of us aspire to healthy aging, regardless of the presence of age-related impairments or disabling conditions. The experience of growing older with a disability and growing older into a disability may differ\u2014in part because of the different dynamics of ageism and ableism and the differences in economic and social conditions that result\u2014but these life course trajectories present similar challenges and opportunities. In this document we seek common ground, in terms of the modern conception of active aging and of disability, defined as difficulty in functioning at the body, person or societal levels experienced by an individual with a health condition in interaction with the person\u2019s physical, social and attitudinal environment. Moreover, we firmly believe that, despite the distinctions between aging and disability created by professionals, academics, advocacy NGOs, public policies and government agencies, the time has come to emphasize similarities in experiences and needed supports, services and policies rather than focusing on differences. Distinctions between early and late onset of disability are to a large extent a reflection of policy issues\u2014with various utilities across nations\u2014but they do provide a picture of the parameters of practice and research that can inform bridging and consequences of this distinction.This declaration builds upon the Barcelona Declaration on Bridging Knowledge in Long-Term Care and Support, March 5\u20137, 2009, the Graz Declaration on Disability and Ageing, 9th June, 2006, the Linz Declaration as well as United Nation\u2019s Conventions and international directives that recognize the human rights and the biopsychosocial approach to disability. Bridging encompasses a range of concepts, tasks, technologies and practices aimed at improving knowledge sharing and collaboration across stakeholders, organizations and fields in care and support for persons with disabilities, their families, and the aging population. Bridging tasks include activities of dissemination, coordination, assessment, empowerment, service delivery, management, financing and policy. The overall purpose of bridging is to improve efficiency, equity of care, inclusion and support at all levels, from the person to the society. It is also an issue of recognition of the complexity of the human condition from birth to death, the capabilities of all people, and the need for a conceptual vision that takes into consideration planning for a society where participation of all citizens is the ultimate goal.National and international bridging of aging and disability knowledge, policy and practice must be actively promoted. Aging with and aging into disability are global population trends. Cross-national and international collaborations can support effective and efficient knowledge development and transfer, implementation of best practices, and facilitate information exchange among and empowerment of persons with disabilities and their families.Bridging is composed of several activities which must occur simultaneously, at multiple levels of knowledge development, policy and practice, and include disability and aging stakeholder groups. The scope of required bridging activities is broad, including the analysis of public policies, interdisciplinary research, the development of professional best practices, and coalition building across advocacy groups and among individual stakeholders. Older adults and people with disabilities and their families must be meaningfully included in bridging activities in recognition of their rights to self-determination and social inclusion.Building effective bridges across aging and disability knowledge, policy and practice requires interdisciplinary collaboration and engagement with national and international decision-makers. Development of effective models of bridging and successful bridging practices requires engagement of professional and citizen stakeholders bringing together relevant knowledge and experience. Decision leaders must engage knowledge brokers to pursue program and policy changes that support bridging activities.Connecting the field of aging and disability will require development of a clear model of bridging. Research at all levels will support the science of bridging as it develops. However, research must give immediate and persistent attention to the pace of bridging to assure that it aligns with the needs of the person aging with disability in order for them to negotiate and make life choices, navigate support and service systems, and engage in opportunities for full inclusion and participation in society.Bridging requires developing a common terminology and knowledge base. Tasks include activities of dissemination, coordination, assessment, empowerment, service delivery, management, financing and policy. Technologies include various Information Technologies, assessment instruments and guidelines. Bridging practices should be catalogued and incorporated to open-access repositories for use by aging and disability networks.Improved access to healthcare services; improved diagnosis and treatment of secondary conditions and diseases; care coordination; health literacy; health promotion and wellness; prevention of age-related chronic conditions; prevention of abuse and neglect; reduction in pre-mature mortality and training of health professionals in aging and disability.Accessible societies, including age and disability friendly communities, removal of barriers of any kind: architectural, cultural, legislative. Impact and implications of aging and disability on civic and community engagement, and the role of technology and universal design in fostering inclusion, participation and knowledge management.Support for families and caregivers, training and education of direct support professionals; self-determination, access, availability, and affordability of supports and services; ethical issue related to non-discrimination, such as in palliative care, end of life issues.Employment, retirement security, asset development; accommodation and accessibility in the work setting; value of non-paid social and community contributions.Research on bridging aging and disability and on ways to transfer this knowledge locally, nationally, and internationally to policy development.An international agenda for bridging aging and disability be formally developed through the involvement of researchers, practice professionals, policy-makers, older adults, persons with disabilities and their families.Public and private funders provide financial support for research and scholarship that advances the science of bridging aging and disability knowledge, practice and policies.Health and social policy-makers incorporate bridging and knowledge transfer as key strategies in policy planning for building a society where all citizens can fully participate including persons with disabilities of all ages.The authors, all of whom were participants at the Growing Older with a Disability conference at FICCDAT 2011, endorse this Declaration and invite feedback.Response can be sent to the attention of Toronto Declaration@marchofdimes.ca\u2018TD Endorsement\u2019 in the subject line.Individuals and organizations which have endorsed this declaration are listed below. Others are invited to add their endorsement by sending an email with your full contact information to TorontoDeclaration@marchofdimes.ca, adding Most importantly, we call upon governments, practitioners, policy-makers and academics to work together with consumers and their families to ensure attention and implementation of the preceding recommendations.Co-Chairs of Growing Older with a Disability (GOWD) conference, Festival of International Conferences on Caregiving, Disability, Aging and Technology (FICCDAT), 2011Margaret Campbell, PhD, Jennifer Mendez, PhD, Sandy KeshenJerome E. Bickenbach, PhDDepartment of Health Sciences and Health Policy, University of Lucerne and Schweizer Paraplegiker-Forschung, Nottwil, SwitzerlandChristine Bigby, PhDDepartment of Social Work and Social Policy, La Trobe University, Bundoora, Victoria, AustraliaLuis Salvador-Carulla, MD PhDFaculty of Health Sciences, University of Sydney, Sydney, AustraliaTamar Heller, PhDRehabilitation Research and Training Center on Aging with Developmental Disabilities, University of Illinois at Chicago, Chicago, IL, USAMatilde Leonardi, PhDHead Neurology, Public Health, Disability Unit Foundation IRCCS Istituto Neurologico Carlo Besta, Milan, ItalyBarbara LeRoy, PhDDevelopmental Disabilities Institute, Wayne State University, Detroit, Michigan, USAJennifer Mendez, PhDSchool of Medicine, Wayne State University, Detroit, Michigan, USAMichelle Putnam, PhDSchool of Social Work, Simmons College, Boston, USAAndria Spindel, MSWMarch of Dimes Canada, Toronto, CanadaEuropean Association of Service Providers for Persons with Disabilities (EASPD).The Graz Declaration on Disability and Ageing. Graz, Austria, June 9, 2006. http://www.easpd.eu/LinkClick.aspx?fileticket=eDUBIDI0HSU%3D&tabid=3531.Salvador-Carulla, L., Balot, J., Weber, G., Zelderloo, L., Parent, A.S., McDaid, D., Solans, J., Knapp, M., Mestheneos, L., Wolfmayr, F. Participants at the Conference. (2010).The Barcelona Declaration on bridging knowledge in long-term care and support. Barcelona (Spain), March 7, 2009. International Journal of Integrated Care, April 12.http://www.ijic.org/index.php/ijic/article/viewArticle/521/1035European Association of Service Providers for Persons with Disabilities (EASPD).The Linz Declaration: Independent living for ageing persons with disabilities. Linz, Austria, January, 2012.http://www.poraka.org.mk/en/2012/EASPD%20Linz%20Declaration%202011.pdf.World Health Organization.World Report on Disability. Geneva, Switzerland, 2011. (Joint Publication of The World Bank.) http://whqlibdoc.who.int/publications/2011/9789240685215_eng.pdf.United Nations.Convention on the Rights of Persons with Disabilities. New York, USA. December 13, 2006http://www.un.org/disabilities/convention/conventionfull.shtml.United Nations.Political Declaration and Madrid International Plan of Action on Ageing.Madrid, Spain, 2002.http://social.un.org/index/Portals/0/ageing/documents/Fulltext-E.pdf.http://www.ficcdat.ca/main.cfm?cid=1793.To download a copy of the Toronto Declaration, learn about presentation dates, and to endorse this declaration, please visit the FICCDAT website at www.ficcdat.ca (click on Growing Older) or click here"} +{"text": "The affiliation for the third and fourth authors is incorrect. Daouda A. K. Traore and Lan Gong are affiliated not with institution number 2, but with institution number 1, Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, Australia."} +{"text": "The authors would like to make the following corrections.Cartagena's University Hospital del Caribe instead of Cartagena's University, second column, 29th line, it should be Bogota, instead of Cartagena.In page 2, paragraph 2, Materials and Methods, first column, 34th line, it should be"} +{"text": "There were errors in two affiliations and in the Funding statement of the article.Affiliations 3 and 6 should read, respectively:3 German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum M\u00fcnchen, Munich-Neuherberg, Germany,6 Institute for Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany,The Funding statement should read: This work was funded by grants from AIRC , Fondazione Monzino and Fondazione Ferrari to PPDF, and by grants from the German Federal Ministry of Education and Research and the European Union (EUMODIC LSHG-2006\u2013037188). SC is supported by the Italian Foundation for Cancer Research (FIRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."} +{"text": "There was an error in the affiliation for Maria Antonietta Ajmone-Cat. The correct affiliation is: Section of Experimental Neurology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit\u00e0, Rome, Italy"} +{"text": "The affiliation of last author is incorrect. Kumarasamy Thangaraj is not affiliated with institution number 1, but with institution number 3, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India."} +{"text": "The affiliation for the twentieth author was incorrect. Mary Carrington is not affiliated with #10 but with #12 Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America. The author\u2019s affiliation to #18 is unaffected."} +{"text": "After publication of this work , we noteThe authors declare that they have no competing interests.HH, JK, RS, MH, AA, MB, WE, TC, AG, AK and MR conceived of the study and participated in its design and coordination. JK and HH made substantial contributions to conception and design of the manuscript as well as data acquisition. MH, MB, TC, AG have been involved in drafting the manuscript. RS and MR were involved in revising the manuscript. All authors read and approved the final manuscript."} +{"text": "An affiliation for the sixth author is incorrect, and an affiliation for the sixth author is missing. Stefania Boccia is affiliated with the following institutions: Section of Hygiene, Institute of Public Health, Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy; IRCCS San Raffaele Pisana, Rome, Italy."} +{"text": "Journal of Venomous Animals and Toxins[Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD) with ISSN 1678\u20139199. The journal finally became online-only[Science Citation Index Expanded\u2122[The nd Toxins, ISSN 01nd Toxins of UNESPnd Toxins. In 2003ine-only and was xpanded\u2122 and ScopJVATiTD has been experiencing significant growth since 2006, in which year 52 articles were published with a rejection rate of 11.86%. The rejection rate has subsequently increased year after year, reaching 41.33% in 2012. The average elapsed time between submission and acceptance from 2007 to 2012 was 135, 139, 133, 88, 86 and 78\u2009days; the respective elapsed time between acceptance and publication was: 196, 143, 170, 132, 95 and 84\u2009days; the overall time between submission and publication was: 331, 282, 303, 220, 181 and 162\u2009days.Thus, the elapsed time between submission and acceptance is shorter than the one between acceptance and publication. This analysis leads to the conclusion that the speed and visibility of publication have risen significantly in the last five years, given that the current average time between submission and publication is similar to that of journals with higher global impact, that is, only 162\u2009days.As a consequence of these achievements, there has been a substantial increase in the submission of articles, especially after indexing of the journal in the Journal Citation Reports\u00ae (JCR). JVATiTDScience Citation Index ExpandedTM[Finally, a partnership with BioMed Central \u2013 The OpxpandedTM, e-DepotxpandedTM, CrossRexpandedTM, QuertlexpandedTM, SCIRUSxpandedTM and WebcxpandedTM.This partnership with BioMed Central will, beyond the shadow of a doubt, increase our impact factor and, consequently, improve our journal classification worldwide.The author declares no conflicts of interest."} +{"text": "Precipitation in Sahel was low during warm climate regimes. Spectra coherence of changes in precipitation in Sahel with ENSO was significant at p\u2009<\u20090.0001. ENSO and PDO are determinants of the seasonal, interannual, and interdecadal changes in occurrence of meningococcal meningitis. Public health management of epidemics of meningococcal meningitis should include forecast models of changes in ENSO to predict periods of low precipitation, which initiate occurrence.Meningococcal meningitis is a major public health problem that kills thousands annually in Africa, Europe, North, and South America. Occurrence is, however, highest during the dry seasons in Sahel Africa. Interannual changes in precipitation correlate with interannual changes in El Ni\u00f1o-Southern Oscillation (ENSO), while interdecadal changes in precipitation correlate with Pacific Decadal Oscillation (PDO). The objective of the study was to determine if there is spectral coherence of seasonal, interannual, and interdecadal changes in occurrence of meningococcal meningitis in Sahel, Central, and East Africa with interannual and interdecadal changes of PDO and ENSO. Time series were fitted to occurrence of meningococcal meningitis in Sahel, Central, and East Africa, to indices of precipitation anomalies in the Sahel, and to indices of ENSO and PDO anomalies. Morlet wavelet was used to transform the time series to frequency-time domain. Wavelet spectra and coherence analyses were performed. Occurrence of meningococcal meningitis showed seasonal, interannual, and interdecadal changes. The magnitude of occurrence was higher during warm climate regime, and strong El Ni\u00f1os. Spectra coherence of interannual and interdecadal changes of ENSO and PDO with occurrence of meningococcal meningitis in Sahel, Central, and East Africa were significant at Neisseria meningitidis, which is non-spore-forming, non-motile, gram-negative cocci. While headache, fever, nausea, and vomiting occur in meningococcal meningitis as in other febrile illnesses, shock, petechiae and purpuric skin rashes are its major characteristics , determine changes in precipitation in the Sahel , severalCountries in the Sahel are Senegal, Gambia, Guinea, Mauritania, Mali, Benin, Burkina Fasso, Nigeria, Cameroon, Niger, Tchad, Sudan, and Eritrea; countries in Central Africa are Burundi, Central African Republic, Rwanda, Angola, Congo, Democratic Republic of the Congo, Sao Tome and Principe, Equatorial Guinea, and Gabon; while countries in East Africa are Tanzania, Uganda, Ethiopia, Djibouti, Kenya, Somalia, Comoros, Malawi, Zambia, Zimbabwe, Seychelles, Mozambique, Madagascar, and Mauritius.http://ggweather.com/enso/oni.htm. Ranks of El Ni\u00f1o from 1871 to 1949 from http://www.esrl.noaa.gov/psd/enso/mei.ext/rank.ext.html, and from 1950 to 2014 from http://www.esrl.noaa.gov/psd/enso/mei/table.html. Pacific Decadal Oscillation Index was downloaded from the Joint Institute for the Study of the Atmosphere and Ocean Arctic Oscillation websiteMultivariate El Ni\u00f1o-Southern Oscillation Index (MEI) data, which were computed from sea-level pressure, zonal and meridional components of the surface wind, sea surface temperature, surface air temperature, and total cloudiness fraction of the sky of the South Pacific Ocean from 195Sahel precipitation data from 1900 to 2013 were obtained from the Joint Institute for the Study of the Atmosphere and Ocean . The preMonthly data of occurrence of meningococcal meningitis cases in the Sahel, from 2006 to 2014, were obtained from World Health Organisation Weekly Meningococcal Meningitis Surveillance BulletinsTime series were fitted to indices of ENSO, PDO, and Sahel precipitation, and to occurrence of meningitis. Autocorrelation and partial autocorrelation tests, and lag plots were applied to exclude white noise and to inspect for seasonality. Stationarity was assessed using the unit root test. To determine month of peak occurrence of meningitis annually, the monthly data from 2006 to 2014 were rescaled to 0\u20131 values for each year, and plotted.\u03c90 is dimensionless frequency, and \u03b7 is dimensionless time, was used to transform the time series. The continuous wavelet transform of time series \u03b4t was defined as the convolution of nx with the scaled and normalized wavelet (vZ (p) was the confidence level associated with probability p, and Wavelet methods which have been applied to epidemiological , 18, hum wavelet , 18. The wavelet , 18:D|Whase was , 18Rn2, but meningococcal meningitis did not Granger cause ENSO series (p\u2009>\u20090.05).Granger causality test showed that ENSO Granger caused meningococcal meningitis series (Pandemics or major epidemics of meningococcal meningitis occurred in 1905 in West Africa , in the Precipitation was above the mean from 1950 to 1970, during cool climate regime, but below the mean from 1972 to 1998 during warm climate regime (Figure p\u2009<\u20090.0001 (Figure p\u2009< 0.0001 (Figure Global spectra from 1945 to 2013 showed peaks at 1.0, 3.0, 6.0, 12.0, and 20\u2009years for precipitation changes in Sahel, but at 3.0, 6.0, 12.0, and 20.0\u2009years for ENSO (Figure This study shows periodic changes in occurrence of meningococcal meningitis and indices of ENSO and PDO. Periodic changes in occurrence of meningococcal meningitis have been observed in the USA , in UnitThe spectra of monthly time-series in Sahel, which show similar time-varying periodicities of 6 and 12\u2009months with the spectra of ENSO, indicate that both variables share rhythms at similar timescales Figure . Strong In the past century cool climate regimes occurred from 1890 to 1924 and from 1947 to 1976, while warm climate regime occurred from 1925 to 1946, and from 1977 to 1998 . Time seWavelet analysis, which transforms time series to time-frequency domain, has shown the time-varying nature of PDO . During Cycles of occurrence of meningococcal meningitis in Sahel, Central, and East Africa show that El Ni\u00f1os were accompanied by high peaks of occurrence, while La Ni\u00f1as were accompanied by low peaks of occurrence. Furthermore, phases of occurrence are right shifted relative to that of ENSO Figure . Thus, pPeriodicity of the ENSO, like the PDO, is time-varying. Periodicity of ENSO, which was 3\u20134\u2009years from 1872 to 1910, was 5\u20137\u2009years from 1911 to 1960, but 5\u2009years from 1970 to 1992 . The perHistorical data showed that pandemics or major epidemics of meningococcal meningitis occurred in 1905 in Nigeria , in 1918Meningococci are commensals of the nasopharynx, but minority of strains cause invasive infection . The risCyclicity of meningococcal meningitis epidemics was correlated with sunspots cycles in Bulgaria in 2000 and in tENSO activity has been correlated with the monsoons . Since 1Since virulence of organism, innate immunity, carriage, overcrowding, and other risk factors were not controlled for in this study, the peaks of occurrence in the time series cannot be attributed to climate alone. Immunization, for example, is expected to contribute to reduction of number of potential cases. Although there are many potential confounding factors, the WHO has documented that these confounding factors are unlikely to consistently covary with ENSO in long time-series . Thus, tWavelet methods have been used to correlate ENSO activity with periodic epidemics of malaria in West Africa , choleraThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author\u2019s initial, TM, is missing from the funding statement. The correct funding statement is given below.This study was supported by a grant-in-aid for scientific research from the Japan society for the promotion of science; YF, HN, TM, MM. This study was supported by MEXT/JSPS KAKENHI Grant Numbers 23390057, 26293054, 25860061 and 22590160. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."} +{"text": "Datura, family Solanaceae, consists of nine species, originating from the New and Old World [After the publication of this work , it was ld World \u201d, \u201corigi"} +{"text": "Afterwards, 0.66 and 0.33 \u03bcCi ml\u22121L-[3H]glutamate were added to a final 100 \u03bcM concentration of glutamate for incubation with hippocampal and cortical samples, respectively.\u201d This correction does not affect the scientific relevance of the results.In the subsection \u201cGlutamate Uptake Assay,\u201d the greek letter micro (symbol \u03bc) was accidentally deleted twice probably due to software incompatibility. The correct sentence should read: \u201cEZ was responsible for the design, acquisition, analysis, interpretation, drafting, and approval of the final version of the manuscript. VT, EK, MA, KZ, RA, and GH were responsible for acquisition, analysis, interpretation, and approval of the final version of the manuscript. AM, DS, and RM were responsible for interpretation, drafting, critical revision, and approval of the final version of the manuscript. LP was responsible for the design, interpretation, drafting, critical revision, and approval of the final version of the manuscript.This work was supported by the following Brazilian agencies and grants: National Counsel of Technological and Scientific Development (CNPq), CAPES, FAPERGS, Brazilian Institute of Neuroscience (IBNnet), FINEP, and National Institute of Science and Technology (INCT) \u2013 Excitotoxicity and Neuroprotection.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The affiliation for the second author is incorrect. Lifah Sanudi is affiliated with REACH Trust, Lilongwe, Malawi, not with SINTEF Technology and Society, Oslo, Norway.The publisher apologizes for the error."} +{"text": "The microenvironment of malignant gliomas is described according to its definition in the literature. Beside tumor cells, a series of stromal cells represents the cell component, whereas a complex network of molecular signaling represents the functional component. Its most evident expressions are perivascular and perinecrotic niches that are believed to be the site of tumor stem cells or progenitors in the tumor. Phenotypically, both niches are not easily recognizable; here, they are described together with a critical revision of their concept. As for perinecrotic niches, an alternative interpretation is given about their origin that regards the tumor stem cells as the residue of those that populated hyperproliferating areas in which necroses develop. This is based on the concept that the stem-like is a status and not a cell type, depending on the microenvironment that regulates a conversion of tumor non-stem cells and tumor stem cells through a cell reprogramming. It includes, therefore, many cell types, such as endothelial cells, microglia/macrophages, reactive astrocytes, fibroblasts, pericytes, immune cells, etc., and the etc., and defeetc., ,4.+ and CD133+ stem cells, which condition angiogenesis and tumor growth [Any regulation of tumor cells towards regression, such as necrosis, or progression, such as proliferation, invasion and angiogenesis, finds its main driver in the microenvironment that mainly expresses itself in the so-called niches ,4,5. As r growth , or as mr growth or by sir growth . Positivr growth . C6 glior growth .PNN have been described to develop around circumscribed necroses where hypoxia and HIF-1/2 play a cvia nitric oxide and Notch activation [etc., [PVN are not merely repositories of stem cells , but thetivation ,6,15, whtivation . In PVN,tivation ,17,18,19tivation ,21,22,23n [etc., .in vitro neurosphere formation and xenographts [etc., as well as the intrinsic signaling such as Wnt/\u03b2-catenin, Bmi1, c-Myc, Oct4, OLIG2, Sonic Hedgehog (SHH), and Notch.Hypoxia, a mechanism of primary importance in the biology and aggressive behavior of malignant gliomas , is fundographts . Hypoxiaographts . GSCs arographts ,8. In thi.e., by transformation of the normal neural stem cells (NSCs) and progenitors in relation with the so-called glioma initiating cells (GICs), the concept of which is just mentioned here. In line with the old belief that cancer cells are similar to embryonic stem cells [i.e., from primitive neuroepithelial cells or NSCs [In the discussion of the tumor microenvironment, it is mandatory to consider the supposed origin of GSCs, em cells , it has em cells ,32, i.e. or NSCs . GICs sh or NSCs ,35,36, e or NSCs .i.e., on genotypic and phenotypic differences acquired during proliferation, migration, also by epigenetic mechanisms [Other possibilities are the origin of GSCs from oligodendroglial precursor cells (OPCs) or NG2 cells ,39,40,41chanisms ,50 and, i.e., PVN and PNN. Theoretically and conceptually, the niches have been very well-defined [From the neuropathological point of view, the concept of microenvironment in gliomas materializes in its main expression sites, -defined ,4,5, but-defined or by fl-defined . One of -defined ,52. In a-defined .i.e., that necrosis is due to the imbalance between the high proliferation rate of hyperproliferating areas of the tumor and the low one of endothelial cells [As for PNN, we showed that, at variance with the activation of GSCs by hypoxia through HIF-1/2 ,8, the tal cells . Cell deIn conclusion, microenvironment by genetic and epigenetic mechanisms regulates the equilibrium between tumor stem cells and tumor non-stem cells so that the occurrence of GSCs would not imply the existence of a special type of cells, but it would be the consequence of an interplay that takes place in the microenvironment . This wo"} +{"text": "Parkinson's disease (PD) is an example for a complex field of research, which is driven by the multifactorial etiology, the heterogeneity in phenotype and the variability in disease progression, as well as the presence of a long pre-diagnostic period, called prodromal PD, lasting up to decades of the Joint Programme for Neurodegenerative Diseases (JPND), set out to develop an assessment battery that includes the most useful clinical, laboratory, and brain imaging assessments for studies in PD.Based on the need for harmonized assessments of symptoms/markers in PD, the working group: We here describe the result of the process to find a way to harmonize assessments across studies and propose a modular set of biomarker assessments agreed upon by the group of experts who were included in the working group .As a first step, information about the design, markers, and assessments of 21 ongoing cohort studies in various phases of PD represented by members of the JPND working group were collected using a detailed questionnaire. These data served as a basis for the project. Detailed results have been reported previously in Lerche et al. . In a sebasic module , a minimum function and assessment module and several optional extension modules.Based on the analyses, the JPND BioLoC-PD working group suggests the following three-level modular assessment battery to be implemented in new and whenever possible ongoing longitudinal studies for PD Figure . The setbasic module is meant to be applied to all participants in longitudinal studies in PD. It may also be applied to existing registers and patients seen routinely in outpatient clinics irrespective of whether they are currently recruited for a longitudinal study. It may also be used for retrospective analyses or identification of potential eligible participants for future randomized controlled trials.The minimum module is suitable for all individuals participating in at risk, prodromal, and clinical longitudinal studies of PD. The functions of the minimum module are in a descending order (sorted by their use within the BioLoC-PD working group). Functions used in all PD studies are at the beginning of each of the lists (in the minimum and extension modules). Modes of assessment of these symptoms are based on the frequency and applicability within studies . Each of the assessments suggested for the minimum module . In case of the imaging module the methods are in a descending order with the one on the top preferred by the BioLoC-PD consortium.The We propose, that each study should as a minimum requirement collect the data specified in the basic module. The basic module is valuable also for genetic or other non-clinical analyses. Once individuals are clinically examined, several motor and non-motor domains should be covered, as suggested in the minimum module which also comprises additional data about medical history. Finally, according to the main research aim of the study, different extension modules can be added.In general, we provide researchers with suggestions for specific assessment tools/scales to allow comparison across studies. For the cognition module, however, it is less important which assessments are used rather, it is important to take a minimum of two tests per domain for a sensitive and specific diagnosis of dementia and Mild Cognitive Impairment (MCI) level II Not all scales/questionnaires are available and validated in all languages. (ii) Study designs vary with regard to outcome variables which influences the choice of assessments. (iii) Some assessments require more resources than others , which also influenced the selection and composition of the selected assessment battery. (iv) Advances in knowledge about assessments and biomarkers have led to revision or expansion of assessments after the respective study was initiated. (v) Preference for a specific assessment based on previous experience of the individual researchers involved.With our proposed modular set of biomarker assessments, we propose a concept by which we hope to overcome the problem of data comparison due to lack of harmonization and set the stage for broad data sharing, joint data analyses and acceleration of biomarker research.SL, SH, GA, PB, SB, YBS, HB, BRB, DBu, RD, DG, GH, MH, MK, RK, ILS, WM, MM, BM, WO, BR, UW, KW, DBe substantial contributed to the conception and design of the work; SL, SH, DBe drafted the work; GA, PB, SB, YBS, HB, BRB, DBu, RD, DG, GH, MH, MK, RK, ILS, WM, MM, BM, WO, BR, UW, KW revised the work critically for important intellectual content; SL, SH, GA, PB, SB, YBS, HB, BRB, DBu, RD, DG, GH, MH, MK, RK, ILS, WM, MM, BM, WO, BR, UW, KW, DBe gave their final approval to the version to be published; SL, SH, GA, PB, SB, YBS, HB, BRB, DBu, RD, DG, GH, MH, MK, RK, ILS, WM, MM, BM, WO, BR, UW, KW, DBe agreed to be accountable for all aspects of the work.The work was funded by the EU Joint Programme\u2014Neurodegenerative Disease Research (JPND) program (BMBF No:01ED1410).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Each September since 2004, the Federal Emergency Management Agency (FEMA) has observed National Preparedness Month. During September, FEMA and various local, state, and federal agencies encourage U.S. residents to become better prepared for emergencies and disasters. Approximately 3,000 organizations, including the American Red Cross, Citizen Corps, and CDC , are schOn this 10th anniversary of National Preparedness Month, CDC also is recognizing the first decade of activity of its Emergency Operations Center . Staffedhttp://www.cdc.gov/phpr.All persons can take important steps to prepare themselves, their families, and loved ones for a possible disaster. CDC has various tools and checklists to help everyone \u201cbe ready\u201d at home, at places of work and worship, and within the larger community . Additio"} +{"text": "This article was republished on August 7, 2014, to replace incorrectly changed characters in the byline, Competing Interests statement, Author Contributions, and Acknowledgments in the online version only. The publisher apologizes for the errors."} +{"text": "The National Congress of Surgery, one of the annual events to which the surgeons in all the surgery units in Romania gather to share the experience and to learn from one another took place this year, in Sinaia, the most beautiful mountain resort, during 21-24th of May 2014. \u201cCasino Sinaia\u201d International Conference Center offered through the great hall (the Theater) and four other halls, a sumptuous background, elegant and, in the same time, a proper place for the event. What should be mentioned is the fact that this Romanian traditional medical scientific event has taken place under the high patronage of His Excellency, Victor Ponta, Prime Minister of Romania. The main Congress organizer was the Romanian Society of Surgery in collaboration with the Academy of Medical Sciences, Romanian Association of Hepato-Biliopancreatic Surgery and Liver Transplantation, Romanian Association of Endoscopic Surgery and other Intervention Techniques, Romanian Society of Emergency Surgery and Traumathology, Romanian Society of Breast Surgery, Romanian Society of Thoracic Surgery, Romanian Society of Pediatric Surgery, Romanian Society of Medical Assistants in Romania, Romanian Students\u2019 Society of Surgery. What should be highlighted from the beginning is the high number of participants, surgeons from Romania and from abroad (over 1500) and over 300 students from all the universities in Romania, who successfully represented the Romanian Students\u2019 Society of Surgery. Wednesday, the 21st of May 2014, was allocated to the eight pre-congress post university courses and, due to their importance and the special participation, we should shortly enumerate their content and the speakers, who are remarkable personalities in their field: C1 \u2013 The surgical rectum anatomy; critical points in rectum surgery ; C2 \u2013 Controversies in rectum surgery ; C3 \u2013 The minimally invasive rectum cancer surgery ; C4 \u2013 Causes of failure in the rectum cancer surgery ; C5 \u2013 The surgery of the breast cancer ; C6 \u2013 The multimodal treatment of breast cancer ; C7 \u2013 The reconstruction of the breast after mammectomy \u2013Allergan Symposium; C8 \u2013 RSEST - MUSEC European Course; Ultrasound in trauma and emergency ; What should also be mentioned is MUSEC European competence course, organized by the Romanian Society of Emergency Surgery and Traumatology - RSEST \u201cUltrasound in trauma and emergency\u201d, having prof. Mauro Zago, MD, from Bergamo responsible for the course and also the lecturers Andrea Cassamassima (Milano), Mateo Zarcani (Milano) and Mihai P\u0103duraru (Tomelosso), all from Italy, a course to which subscriptions have been made a lot of time before, due to the limited number of participants given by the type of the workshop. This year\u2019s congress has guided itself on two main themes: \u201cThe complex treatment of rectum cancer\u201d and \u201cBreast cancer. Complex treatment. The reconstructive surgery of the breast\u201d. The scientific program was not limited only to these two themes and (due to the inherent monotony which appears in the monothematic congresses), has contained and varied also video laparoscopic surgery, hepato-biliopancreatic surgery, endocrine eso-gastric surgery. Fully, over 500 papers were presented in the 5 halls of the congress which benefited from the necessary modern infrastructure. The festive opening of the Congress took place on Thursday evening, the 24th of May, in the presence of the Ministry of Health, His Excellency Nicolae B\u0103nicioiu , the mayor of Bucharest, prof. Sorin Oprescu, MD , prof. Florian Popa, MD , prof. Vasile Ast\u0103r\u0103stoaie, MD (president of the College of Physicians in Romania), prof. Mircea Beuran, MD (elected president of RSS), prof. Eugen Br\u0103tucu, MD . In their presentations, the members of the presidium have highlighted the difficulty of undertaking a medical and surgically correct and decent act for the patient, taking into account the crisis in the Romanian medical system, suggesting diverse solutions, among which, the one of Senator, prof. Florian Popa, MD, regarding the liberalization of the physician profession in Romania. The way of development of the congress was based on novelty, according to a European model, less mini oral papers being selected, the other ones migrating to posters, the \u201cstate of the art\u201d presentations and round tables having priority, with interdynamic development of the discussion themes, having the expected success. The rectum surgery was one of the main themes of the congress and raised a special interest. The following sessions led by prof. \u015etefan Georgescu, MD, prof. Traean Burco\u015f, MD, assoc. prof. C\u0103t\u0103lin Vasilescu, prof. Laz\u0103r Fulger, MD, prof. Adrian Magyar, MD, assoc. prof. Victor Str\u00e2mbu, MD, C\u0103t\u0103lin Cop\u0103escu, MD, prof. Silviu Constantinoiu, MD should be mentioned. The round tables on the same subject were mediated by prof. C. Copotoiu, MD, prof. Tr. P\u0103tra\u015fcu, MD, prof. V. Scripcariu, MD, assoc. prof. Dan Straja, MD, prof. Mircea Beuran, MD, as well as the one regarding radiochemotherapy in rectum cancer , or colonic surgery and have been the most interesting for the participants. The rectum minimally invasive surgery has raised a special interest, like the other themes did, such as the total resection of the mesorectum, the anatomo-pathological examination of the resection part, the complications of rectum surgery. The sessions allocated to the breast surgery have completed the themes approached in the pre-congress courses highlighting the ones led by prof. Eugen T\u00e2rcoveanu MD, prof. \u015etefan Neagu, MD, prof. Ion A\u015fchie, MD, assoc. prof. Iulian Brezean, prof. Alex. Irimie, MD, prof. M.R. Diaconescu, MD, prof. Dan Ungureanu, MD, prof. Cristian Lupa\u015fcu, MD. Totally, there were 33 papers and \u201cstate of the art\u201d conferences which approached the theme of breast cancer conservative surgery , sentinel limph node in breast cancer , multidisciplinary treatment of breast cancer , breast oncoplastic surgery, breast cancer surgery with liver metastases, prognosis of breast cancer, Volkman acute carcinomatous mastitis. The round tables have perfectly completed the theme of breast gland pathology: - The oncologic surgery of the breast ;- The actual, diagnostic and therapeutic standards in breast gland cancer (Fl. R\u0103dulescu); - The present coordinates in breast reconstruction after oncologic resections . Two sessions were allocated to hepato-biliopancreatic surgery, summing 26 papers, remarking the ones dedicated to liver tumors , pancreatic tumors , bilio bronchial fistulae (T. Ivanov), Klatskin tumors, liver resections , cephalic duodenopancreatectomy , pancreatic neuroendocrine tumors , liver transplant . Pediatric surgery discussed the disorders due to the migration of the testicle in children, hydatid cysts and the treatment of congenital diaphragmatic hernias in children. The minimally invasive surgery, present mostly in ARCE symposium, has remarked, as usually, through the robotic surgery presentations (assoc. prof. C\u0103t\u0103lin Vasilescu), \u201ebridge to surgery\u201d in colorectal cancer , minimally invasive surgery of the big hiatal hernias . The thoracic surgery session, coordinated by prof. Ioan Cordo\u015f, MD, discussed the minimally invasive thoracoscopic approach, emergency thoracotomy, complex resections of the aerodigestive tract, thymectomy and laparoscopic splanhnicectomy. On Saturday, the 24th of May continued with a session dedicated to gastric surgery , the papers from the \u201cSf. Maria\u201d General and Esophageal Surgery Clinic being remarked , total gastrectomy versus subtotal gastrectomy , GIST (acad. N. Ghidiriu). The esophagus surgery session discussed about high interest and technical problems: minimally invasive esophagectomy , therapeutic strategy in thoracic esophagus squamocellular , the treatment of malignant eso-bronchial fistula through a metallic stent expendably covered . The endocrine surgery session dealt with modern problems regarding parathyroidectomy, thyroidectomy and intraoperative monitorization of the recurrent nerve . Last (but not least), the session \u201cSurgery of the abdominal wall\u201d was very instructive. This review of the congress papers would not be complete if we did not mention the session dedicated to the students\u2019 papers, who were present in a high amount , and who presented papers elaborated in the students\u2019 scientific circles in Romania and at the professors\u2019 guidance. The video film session closed the last day of the congress papers. What should be noticed is the high amount of students and medical assistants taking part in the event, as well as the value of the 264 posters. In the generous setting of the Casino in Sinaia, the medical devices and drugs companies had a functional exposing location. On the occasion of the congress, an editorial event also took place in one of the breaks between the sessions, in the presence of a numerous public, physicians and students: - The launching of the monography \u201cAcute pancreatitis \u2013 clinical-paraclinical approach based on determinant factors\u201d , a paper that makes a connection between Atlanta 1992 criteria and Bologna 2012 criteria. The short speeches of the authors of the two prefaces, prof. Florian Popa, MD, prof. Eugen T\u00e2rcoveanu, MD, as well as the ones of two authors have highlighted the strong points of the paper, which is desired to be useful to all the physicians. - In the same time, \u201cJournal of Surgical Science\u201d for the students and young physicians has been launched; it will appear in English at the initiative of Alexandra Bolocan, MD and \u015fi Dan Nicolae P\u0103duraru, MD, Honorary Editor \u2013 acad. Ioanel Sinescu, rector of \u201cCarol Davila\u201d University Press, Editor-in-Chief \u2013 prof. S. Constantinoiu, MD, Managing Editor prof. Florian Popa, MD, having an Editorial board made up of students and young physicians in Romania, as well as abroad. The magazine proposes to be the national sign of the students\u2019 scientific circles from all the university centers. Moreover, it should be mentioned that these papers appeared in the generous space of \u201cCarol Davila\u201d University Press in Bucharest, General Manager, assoc. prof. dr. Victor Lorin Purc\u0103rea. Moreover, the \u201cSurgery Course for the 4-5th years of study\u201d was elaborated by the professors in the 10th Surgery-Laboratory Department, where the Head of Department is prof. Mircea Beuran, MD. In the RSS General Gathering, important modifications have taken place in the structure of the editorial board of the great magazine of the Romanian surgery, \u201cChirurgia\u201d, the editor-in-chief becoming RSS executive president, validated in the congress, prof. Mircea Beuran, MD, and the editorial secretary being prof. Silviu Constantinoiu, MD, also elected president of RSS. Moreover, 7 vice-presidents of RSS have also been elected, the general secretary , the auditing committee and RSS Directory Committee. We consider that from all points of view, the National Surgery Congress this year has been a real success, reiterating once more the force of the professional organization of the Romanian surgeons, the foreign guests arguing the value of the debates and the presentations, being impressed by the value of the Romanian surgery. Prof. Silviu Constantinoiu, MD Director of the Excellency Center of Esophagus Surgery Head of the General and Esophageal Surgery Clinic \u201cSf. Maria\u201d Clinical Hospital \u201cCarol Davila\u201d University of Medicine and Pharmacy, Bucharest"} +{"text": "Want was inadvertently missed in the original manuscript and we wish to add his name for contribution to ex vivo experiments while MT, DS, and MA assisted in extraction of oil. FA, MI analyzed the data and wrote the manuscript.MI, FA conceived and designed the experiments. MI, FA, GC performed the experiments. MW assisted in The affiliation/correspondence address of the Corresponding author had a minor error, which we hereby rectify. It was incorrectly written as:Department of Medical Laboratories Technology, Faculty of Applied Sciences, Taibah University, PO Box 344, Universities Road, Medina 30001, Saudi ArabiaThe correct version is:Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, PO Box 344, Universities Road, Medina 30001, Saudi ArabiaThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear Editor,A 41-year-old man with history of recurrent airways infection since his childhood, withchronic coughing and voice hoarseness for seven years. The patient was referred toundergo laryngotracheobronchoscopy that revealed the presence of whitish nodular lesionson the anterolateral walls of the trachea and at the most proximal portion of the mainbronchi, whose material was sent for histopathological analysis and 1B. ,2. Association with several factors hasbeen reported, as follows: chronic infections; chemical or medicamentous agents;degenerative tissue alterations; calcium and phosphorus metabolism disorders; andamyloidosis,4.Tracheobronchopathia osteochondroplastica is a rare chronic benign disease, with maleprevalence , and predominantly manifesting between the fifth andseventh decades of life,2,5,6, and therefore, in most cases, thediagnosis is based on incidental findings at bronchoscopy performed to investigate otherdiagnoses or with therapeutic purposes, or even in series of necropsy. In cases of symptomatic disease, coughis the main finding, present in about 66% of cases.The disease is generally asymptomatic,8.Generally, laryngotracheobronchoscopy raises the diagnostic suspicion and the classicalfinding is the presence of whitish, smooth and hard nodules, typically on thecartilaginous walls of the tracheal rings and of the proximal portions of the primarybronchi on the basis of its findings, namely, thickening of the innersurface of the tracheal cartilage with irregular, sessile nodular lesions, eithercalcified or not, focal or diffuse, sparing the posterior (membranous) trachea andleading to luminal narrowing in the affected areas,5,6,8,9. CT is very sensitive to detect the typical calcification ofthe nodules, to define the extent and distribution of tracheobronchial stenosis, as wellas to characterize complications such as atelectasis, bronchiectasis, postobstructivepneumonia,10.The CT contributes to confirm the diagnosis,8.Histopathological analysis shows that nodules correspond to submucosal osteocartilaginousgrowths. There are variable combinations of fibrotic, cartilaginous, bone, hematopoietictissue and mineralized acellular protein matrix. The epithelium lining such nodules maybe normal, or present with inflammatory or meta-plastic appearance,5,8.Some authors consider that bronchoscopic and radiological findings are sufficient toestablish the diagnosis, particularly in cases where it is difficult to performbiopsy.The prognosis is good in most of cases and treatment only will be requested in case ofcomplications, principally tracheal and/or bronchial stenosis"} +{"text": "Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics.Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation.Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation.Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool.Conclusions: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions. Within neurorehabilitation programs, knowledge of the psychological factors associated with pain is crucial for its treatment. In fact, the differential impact of various pathologies on the patient as well as the way in which subjective features can affect the course of the disease and the treatment effectiveness are recognized as important factors that should be assessed in order to successfully treat pain conditions is a multidisciplinary board formed in October 2012, aimed at creating the updated guidelines for the treatment of pain in the field of neurorehabilitation , the names of various disorders that are treated by neurorehabilitation services, the names of psychological factors and the following terms: moderator, mediator, prognostic factor, impact, predictor, outcome. The search identified 159 articles. An update conducted in May 2015 was restricted to the period from 2013 to 2015 and yielded another 93 articles. All these studies were included and were evaluated with the procedure previously outlined.anxiety sensitivity (autonomic anxiety linked to the activation of the body) and anxious perception of pain , University of Genoa, Genoa, Italy; Vittorio Schweiger, Department of Surgery, University of Verona, Verona, Italy; Giorgio Scivoletto, IRCCS Santa Lucia Foundation, Rome, Italy; Nicola Smania, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Claudio Solaro, Neurology Unit, ASL3, Genoa, Italy; Vincenza Spallone, Department of Systems Medicine, University Tor Vergata, Rome, Italy; Isabella Springhetti, Functional Recovery and Rehabilitation Unit, IRCCS Fondazione S. Maugeri, Pavia, Italy; Stefano Tamburin, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Cristina Tassorelli, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy, Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; Michele Tinazzi, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Rossella Togni, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; Monica Torre, IRCCS Santa Lucia Foundation, Rome, Italy; Riccardo Torta, Department of Oncology and Neuroscience, University of Turin, City Hospital Health and Science of the City of Turin, Turin, Turin, Italy; Marco Traballesi, IRCCS Santa Lucia Foundation, Rome, Italy; Marco Tramontano, IRCCS Santa Lucia Foundation, Rome, Italy; Andrea Truini, Department of Neurology and Psychiatry, University Sapienza, Rome, Italy; Valeria Tugnoli, Neurological Unit, University Hospital of Ferrara, Ferrara, Italy; Andrea Turolla, Neurorehabilitation Department, Foundation IRCCS San Camillo Hospital, Venice, Italy; Gabriella Vallies, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Elisabetta Verzini, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Mario Vottero, Neuro-Urology Department, City Hospital Health and Science of the City of Turin, Turin, Italy; Paolo Zerbinati, Neuro- orthopaedic Program, Hand Surgery Department, Santa Maria Hospital MultiMedica, Castellanza, Italy.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are errors in the Funding section. The correct funding information is as follows:\"Funding was provided by the National Natural Science Foundation of China, No. 81471771, 81271686, 81000628, 31000379. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u201d"} +{"text": "This study was aimed to evaluate the relative contributions of spectral and temporal information to Korean phoneme recognition and to compare them with those to English phoneme recognition. Eleven normal-hearing Korean-speaking listeners participated in the study. Korean phonemes, including 18 consonants in a /Ca/ format and 17 vowels in a /hVd/ format, were processed through a noise vocoder. The spectral information was controlled by varying the number of channels whereas the temporal information was controlled by varying the lowpass cutoff frequency of the envelope extractor (1 to 512 Hz in octave steps). A total of 80 vocoder conditions (8 numbers of channels \u00d7 10 lowpass cutoff frequencies) were presented to listeners for phoneme recognition. While vowel recognition depended on the spectral cues predominantly, a tradeoff between the spectral and temporal information was evident for consonant recognition. The overall consonant recognition was dramatically lower than that of English consonant recognition under similar vocoder conditions. The complexity of the Korean consonant repertoire, the three-way distinction of stops in particular, hinders recognition of vocoder-processed phonemes. In vocoder processing or acousMany studies have examined the minimal requirement of spectral information or temporal information for English speech recognition. A general consensus today is that the number of spectral channels required for speech recognition depends on the speech materials. Simple sentences in quiet conditions require only 3 to 4 channels of spectral information for recognition whereas more complex materials (in noise conditions) require 30 or more channels for an equivalent level of performance , 3, 5\u20139.The studies of relative contributions of spectral and temporal cues in English speech recognition have been extended to lexical tone recognition of Mandarin Chinese , 8. The Other than English and Mandarin Chinese, no studies have been done in a different language to confirm or to examine the relative contributions of spectral and temporal information for speech recognition. Korean, spoken by approximately 80 million people, is a nontonal language that is used in the Korean peninsula and in the northeast region of China. In Korean, the consonant inventory includes 22 phonemes and the vowel inventory includes 8 monophthongal phonemes and 12 diphthongs . CompareGiven that there exist such apparent differences in the phonetic inventory between Korean and English and that no studies have been done to examine the spectral and temporal cues for phoneme recognition in Korean, it is important to compare the relative contributions of spectral and temporal information in phoneme recognition of Korean to those of English. The purpose of the present study was to examine the relative contributions of spectral and temporal information to Korean phoneme recognition. The findings, if consistent with those in English, will enable us to extrapolate results from English to other languages. On the other hand, if the findings from the present study indicate discrepancies in the relative contributions of temporal and spectral information between the two languages, it will caution such extrapolations of results from English to other languages and will provide guidance in designing clinical rehabilitation strategies more specifically to Korean.Eleven normal-hearing native-Korean-speaking listeners ages 19 to 26 years old participated in this study. The pure-tone thresholds of each ear of the subjects were < 20 dB HL for octave frequencies between 250 and 8000 Hz. During screening with unprocessed speech materials, consonant and vowel recognition scores were > 90% correct for all subjects. The use of human subjects in the present study was reviewed and approved by the Institutional Review Board of the Seoul National University Hospital. Written informed consent was obtained from all study participants prior to the experiment.h, p*, \u02a7, \u02a7h, \u02a7*, t, th, t*, k, kh, k*, m, n, l, s, s*, h/. Note that Korean consonant /\u014b/ is not used in initial position and the other three approximants /w, j, \u0270/ are often used in diphthongs. Therefore, those four consonants were not used in the consonant stimulus set.Eighteen consonants presented in a /Ca/ context each produced by one male and one female talker were included in the consonant stimulus set: ba, pa, ppa, ja, cha, jja, da, ta, tta, ga, ka, kka, ma, na, la, sa, ssa, and ha. The corresponding International Phonetic Alphabet (IPA) symbols for the consonants are /p, pSeventeen vowels presented in a /hVd/ context each produced by one male and female talker were included in the vowel stimulus set: had, hid, heod, haed, heud, hod, hud, hyeod, hyad, hwad, hyod, hwod, hwid, hyaed, huid, hwaed, and hyud. Note that the stop at the final position in /hVd/ structure is plain and unreleased. The corresponding IPA symbols for the vowels are /a, i, \u028c, \u025b, \u026f, o, u, j\u028c, ja, wa, jo, w\u028c, wi, j\u025b, \u026fi, w\u025b, ju/. Because /\u0265i/, /e/, and /je/ are phonetically similar to /wi/, /\u025b/, and /j\u025b/, respectively, these three vowels were not included in the stimulus set. All speech tokens were recorded in a sound booth with a high-quality microphone . The sampling rate was 44,100 Hz and quantization was set at 16 bits. Individual tokens were isolated and stored in a wave format in a computer hard disk for further processing.f = 165.4 (100.06x \u2212 1), where f is frequency and x is the distance (mm) from the apex of the cochlea ).S1 TableEach Excel sheet contains data from one subject (N = 11). The first column represents talkers with 1 coded for the female and 2 coded for the male talker. Columns 2 and 3 are stimuli and responses with values from 1 to 18 representing ba, cha, da, ga, ha, ja, jja, ka, kka, ma, na, pa, ppa, ra, sa, ssa, ta, and tta, respectively. Column 4 presents the test conditions with number of channels and lowpass cutoff frequency labeled.(XLS)Click here for additional data file.S2 TableEach Excel sheet contains data from one subject (N = 11). The first column represents talkers with 1 coded for the female and 2 coded for the male talker. Column 2 and 3 are stimuli and responses with values from 1 to 17 representing had, hid, heod, haed, heud, hod, hud, hyeod, hyad, hwad, hyod, hwod, hwid, hyaed, huid, hwaed, and hyud, respectively.(XLS)Click here for additional data file."} +{"text": "EANA 2013 took place from the 22nd to the 25th July 2013 in the Faculty of Mathematics and Physics of the University of Szczecin. It was the 13th workshop organized by EANA (European Astrobiology Network Association), an annual event which is hosted in one of the member countries and is recognized to be the most important happening in the astrobiological calendar in Europe.www.astrobiology.pl/eana) started its activity in 2001 with the aim of bringing together European researchers interested in astrobiology programmes and stimulating their collaboration across the borders of different scientific disciplines. Particular attention is directed to introducing young scientists to this interdisciplinary field of studies and to disseminating the results of astrobiological research to its relevant beneficiaries as well as to students and the general public. EANA is a network of 19 European nations active in astrobiology: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Poland, Portugal, Romania, Russia, Spain, Sweden, Switzerland, The Netherlands and United Kingdom. Astrobiology groups in Brazil, China, Japan, Mexico and USA are associated members.EANA (web page: The inauguration of EANA was announced during the First European Workshop on Astrobiology co-organized together with European Space Agency (ESA) at the ESRIN (European Space Research Institute) in Frascati in spring 2001. Since then the astrobiology community in Europe has steadily increased year after year and the regular succession of EANA\u2019s workshops has measured the pace of the research developments in astrobiology. The previous editions of the European Workshop on Astrobiology have been held in the following places:EANA 2001: May 21\u201323, 2001, Frascati, ItalyEANA 2002: September 16\u221219, 2002, Graz, AustriaEANA 2003: November 18\u201320, 2003, Madrid, SpainEANA 2004: November 22\u201325, 2004, Milton Keynes, United KingdomEANA 2005: October 10\u201312, 2005, Budapest, HungaryEANA 2006: October 16\u201318, 2006, Lyon, FranceEANA 2007: October 22\u201324, 2007, Turku, FinlandEANA 2008: September 1\u20133, 2008, Neuch\u00e2tel, SwitzerlandEANA 2009: October 12\u201314, 2009, Brussels, BelgiumEANA 2010: September 6\u20138, 2010, Pushchino, RussiaEANA 2011: July 11\u201314, 2011, K\u00f6ln, GermanyEANA 2012: October 15\u201317, 2012, Stockholm, SwedenThe next Workshop will take place in Edinburgh, United Kingdom, October 13\u201316, 2014.Poland is an EANA member since 2003. On the occasion of the 10th anniversary of Poland\u2019s presence in EANA, the annual EANA workshop was hosted in this country. The Polish astrobiology is represented by CASA* (Centre for Advanced Studies in Astrobiology and Related Topics), which since 2007 is formally organized as a consortium of five Founding Institutions: the Nicolaus Copernicus Astronomical Center (CAMK) of the Polish Academy of Science (PAS) in Warsaw, the Space Research Center (CBK) of PAS in Warsaw, the Institute of Paleobiology of PAS in Warsaw, the Nicolaus Copernicus University in Toru\u0144 and the University of Szczecin. The Headquarters of CASA* is the Faculty of Mathematics and Physics of the University of Szczecin. The main goals of the Centre are to stimulate, perform and coordinate interdisciplinary research in astrobiology in Poland; to develop advanced technologies and to promote their commercial exploitation; to promote the collaboration on astrobiological topics of Polish research teams with other countries in Europe; to train the next generation of astrobiology researchers and to increase the public awareness for science. EANA 2013 has been a very good opportunity to promote astrobiology in Poland.http://eana13.astrobiologia.pl/) was held in the building of the Faculty of Mathematics and Physics of the University of Szczecin near to the beautiful Kasprowicz Park and the historical City Hall. The list of main topics of the meeting is provided below:Astrochemistry, interstellar medium;Astrophysics, protoplanetary discs and planets;Planetary habitability and exploration;Macromolecules and models of prebiotic molecules;Origin and evolution of life, extremophiles;Rocks, fossils and meteorites;Space technology, medicine and industry;Miscellaneous subjects in astrobiology.The 13th EANA Workshop on Astrobiology . [image courtesy of Jerzy Giedrys]The Scientific Organising Committee was composed by the following scientists: Andr\u00e9 Brack, CNRS (France), Axel Brandenburg, NORDITA (Sweden), Charles Cockell, University of Edinburgh (UK), Pascale Ehrenfreund, SPI (USA), Franco Ferrari, CASA*, University of Szczecin (Poland), David Field, Aarhus University (Denmark), Beda Hofmann, Natural History Museum, Bern (Switzerland), Gerda Horneck, DLR Cologne (Germany), Natalia B. Gontareva, St.Petersburg State Polytechnical University (Russia), Zbigniew K\u0142os, SRC, PAS, Warsaw (Poland), J\u00f3zef Ka\u017amierczak, IP, PAS, Warsaw (Poland), Kirsi Lehto, University of Turku (Finland), Jacek Kre\u0142owski, NCU Toru\u0144 (Poland), Helmut Lammer, IWF (Austria), Nigel Mason, Open University (UK), Christian Muller, B.USOC (Belgium), Juan P\u00e9rez-Mercader, Origins of Life Initiative, Harvard University (USA), Petra Rettberg, DLR Cologne (Germany), Heike Rauer, TU Berlin and DLR Berlin (Germany), Gy\u00f6rgyi Ront\u00f3, Hungarian Academy of Sciences, Budapest (Hungary), Alessandra Rotundi, University of Naples \u201cParthenope\u201d , Fran\u00e7ois Raulin, University of Paris 12 and 7 (France), Helga Stan-Lotter, University of Salzburg (Austria), Ewa Szuszkiewicz CASA*, University of Szczecin (Poland), Jorge Vago, ESA (The Netherlands), Frances Westall, CNRS, Orl\u00e9ans (France).To EANA 2013 gathered 118 participants coming from 25 countries . During 10 scientific sessions as many as 49 talks have been delivered, including 12 keynote lectures. Every evening was dedicated to poster viewing. In total 50 posters were presented. Following the tradition, a student contest was organized for the best students\u2019 oral and poster contributions. This year the prize was given to Jan Fr\u00f6sler from the University of Duisburg-Essen in Germany. Furthermore, awards were made to the eight best posters. During EANA 2013 also a special prize of CASA* for the best talks of young scientists has been assigned to Ren\u00e9 Heller and Rafa\u0142 Wieczorek . The scientific contributions to this conference have been collected in this Issue of \u201cOrigin of Life and Evolution of Biospheres\u201d. We are very grateful to Alan Schwartz for making this happen.Several interesting events have been associated with EANA 2013, namely the Public Lecture \u201cOur cosmic genealogy\u201d given by the outstanding Polish astrophysicist prof. Micha\u0142 R\u00f3\u017cyczka from CAMK, the presentation of BRITE-PL - the first Polish Science Satellite performed by the Project Manager Tomasz Zawistowski from CBK and the field trip to the The \u201cMorasko Meteorite\u201d Reserve. The conference dinner included some elements of the molecular cuisine.The Local Organizing Committee would like to thank for support EANA, ESA, the Polish Academy of Sciences, the Polish Ministry of Science and Higher Education, the Polish Astronomical Society, the Committee for Space Research, the Springer publisher, the University of Szczecin, the Faculty of Mathematics and Physics of the University of Szczecin and CASA*. Partial support from the Marshal of the Westpomeranian Voivodeship is also gratefully acknowledged.Picture of the participants in EANA 2013 made in front of the conference venue, the building of the Faculty of Mathematics and Physics of the University of Szczecin. [image courtesy of Jerzy Giedrys]."} +{"text": "The article entitled \u201cAplastic Anemia Associated with Oral Terbinafine: A Case Report and Review of the Literature\u201d, written by Kantarc\u0131o\u011flu et al. and published in a recent issue of your journal, was quite interesting . Here weIn the assessment of 425 cases by van der Klauw et al., the most common causes of drug-related agranulocytosis or neutropenia were, in order, dipyrone, mianserin, sulfasalazine, trimethoprim-sulfamethoxazole, penicillins, cimetidine, thiouracil groups, and phenylbutazone . W,2. W1,2]"} +{"text": "Reason for Corrigendum:The authors, Jeanne A. Rasoamananjara and Louise H. Ralimanana were inadvertently missed in the original manuscript and we wish to add their names for contribution to this work. All authors have agreed to this modification.The authors apologize for this oversight. This error does not change the scientific conclusions of the article in any way.The original article has been updated.ABZ, MH, CS, JM, VG, RWR, SNR, JCR, GR, ROA, RHR, SER, LHR, BR, PG, MCM, JAR, SRA and HD approved the content of Corrigendum.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Torosaurus latus is an uncommon and contentious taxon of chasmosaurine ceratopsid known from several upper Maastrichtian units in western North America. We describe a partial parietal of To. latus from the Hell Creek Formation of Montana. Although the specimen\u2019s ontogenetic maturity means that it cannot inform the ongoing debate over whether To. latus is the old adult form of the contemporary Triceratops, the specimen is one of the best-preserved To. latus parietals and supplements previous descriptions. Torosaurus latus [Triceratops, which is known from dozens of skulls [Torosaurus latus is extremely rare.us latus is a chaus latus . Comparef skulls , 4, ToroTorosaurus latus from the Hell Creek Formation of Montana. The specimen consists of an incomplete parietal and was discovered in 2009 in Garfield County by David Lukens of the Eastern Missouri Society for Paleontology. It was collected from an overbank clay in the middle part of the upper third of the Hell Creek Formation [Here, we describe a new specimen, ESU 2009\u20136, of ormation . ESU 200Torosaurus latus is not a distinct taxon, but rather represents the old adult form of Triceratops [Triceratops, Torosaurus latus represents a rare morphology, and the description of an additional specimen will be highly beneficial. The specimen will be referred to as Torosaurus latus in this paper for ease of communication, with the caveat that To. latus remains a problematic entity.Recently, it has been proposed that ceratops , 6, 7; hceratops \u201310. The ANSP, Academy of Natural Sciences, Philadelphia, PA, USA; EM, Eastend Museum, Eastend, Saskatchewan, Canada; ESU, Emporia State University, Emporia, KS, USA; GP, Glenrock Paleontological Museum, Glenrock, WY, USA; MOR, Museum of the Rockies, Bozeman, MT, USA; MPM, Milwaukee Public Museum, Milwaukee, WI, USA; SMM, Science Museum of Minnesota, St. Paul, MN, USA; YPM, Yale Peabody Museum of Natural History, New Haven, CT, USA.Torosaurus latus [Measurements of ESU 2009\u20136 are provided in the supplementary information . ESU 200Torosaurus latus [The caudal parietal bar is rostrocaudally broad and gently convex along its caudolateral margin, indicating that the complete parietal would have had a rounded shape , similarTorosaurus latus is a derived member of the ceratopsid subclade Chasmosaurinae according to recent phylogenetic analyses that have treated it as a taxon distinct from Triceratops [Torosaurus, To. utahensis from the North Horn Formation of Utah [To. latus. Sampson et al. [Torosaurus including To. latus and To. utahensis, while Longrich [To. utahensis (as \u201cTriceratops utahensis\u201d) to form a clade with Triceratops horridus and Tr. prorsus. The taxonomy and phylogeny of these Maastrichtian chasmosaurines will continue to be refined as additional specimens and new closely related taxa Click here for additional data file."} +{"text": "Dr. Timothy Blanche is not included in the author byline. He should be listed as the ninth author and affiliated with the Allen Institute for Brain Science, 551 N 34th St, Seattle, WA, 98103, United States of America. The contributions of this author are as follows: Contributed reagents/materials/analysis tools, conceived and designed the experiments."} +{"text": "L) of the lung can be divided into two components: the diffusing capacity of the alveolar membrane (Dm) and the pulmonary capillary volume (Vc). DL is traditionally measured using a single-breath method, involving inhalation of carbon monoxide, and a breath hold of 8\u201310 seconds . This method does not easily allow calculation of Dm and Vc. An alternative single-breath method , involving simultaneous inhalation of carbon monoxide and nitric oxide, and traditionally a shorter breath hold, allows calculation of Dm and Vc and the DL,NO/DL,CO ratio in a single respiratory maneuver. The clinical utility of Dm, Vc, and DL,NO/DL,CO in the pediatric age range is currently unknown but also restricted by lack of reference values.The diffusing capacity statistical method.DL,CO,NO and 297 of DL,CO, respectively. Reference equations were established for the outcomes of DL,CO,NO and DL,CO, including the calculated values: Vc, Dm, and the DL,NO/DL,CO ratio.A total of 326 children were eligible for diffusing capacity measurements, resulting in 312 measurements of DThese reference values are based on the largest sample of children to date and may provide a basis for future studies of their clinical utility in differentiating between alterations in the pulmonary circulation and changes in the alveolar membrane in pediatric patients. L). DL for an inhaled gas reactive with hemoglobin is the flow of that gas from the alveoli to the blood for a unit difference in pressure. DL can be divided into two components: the diffusing capacity of the pulmonary membrane (Dm) and the chemical reaction of the gas binding to the blood. The latter is determined by the specific conductance of blood for a given gas, \u0398, and the capillary volume of the lung (Vc).The transfer factor of the lung for a gas, is often called the diffusing capacity of the lung (DL of carbon monoxide (CO) using a breath-hold of 10 seconds is the most frequently used method with the current ATS/ERS methodological guidelines The single-breath method was first introduced in 1915 L,CO,10s, which required arterial samples and two respiratory maneuvers at two different oxygen tensions L,CO,NO) of determining Vc and Dm involving simultaneous inhalation of CO and nitric oxide (NO). Both CO and NO transfer are diffusion limited, but NO has approximately twice the physical diffusivity of CO, and the affinity to hemoglobin for NO (\u0398NO) is approximately 250 times greater \u0398NO was previously assumed infinitely great \u0398NO. The consequence of the use of a finite value for NO blood conductance is that DL,NO appears equally dependent on Dm and Vc as DL,CO is mainly dependent on Vc. In 1957, Roughton and Forster proposed a method of calculating Dm and Vc, using D\u0398gas), but no consensus currently exists about the true value of \u0398CO.The calculation of Dm and Vc involves the resistance of the red blood cell to gas transfer L,NO/DL,CO ratio) L\u0398NO has been determined, new interpretations of the ratio will be necessary.With the previous assumption of an infinite value of L,CO,NO requires a single respiratory maneuver and allows simultaneous determination of DL,CO, DL,NO, as well as calculation of DL,NO/DL,CO, Dm, and Vc. In addition, DL,CO,NO generally involves a shorter breath-hold due to the fast disappearance of NO L,CO,NO,5s). Reference equations for these outcomes of DL,CO,NO,5s in children are scarce. A study involving 50 children over 8 years of age has been published L,CO,10sDetermination of Vc and Dm using DL,CO,NO,5s and DL,CO,10s are two distinctly separate methods, with multiple methodological differences.Despite similarities in the performed respiratory maneuver DL,CO,NO,5s including Dm, Vc, and the DL,NO/DL,CO ratio, in healthy children. Since no consensus guidelines exist for DL,CO,NO,5s and previous data is limited, contemporary measurement of the frequently used DL,CO,10s was performed to allow assessment of correlation between these two substantially different techniques and to assess whether they could be used interchangeably, although, knowing for a fact, that significant methodological differences exist. The resulting measurements of DL,CO,10s allowed establishment of reference equations and comparison with existing published reference equations for DL,CO,10s. Some of the results of this study have been previously reported in the form of an abstract The primary goal of this study was to calculate reference equations for the outcomes of DThe regional ethics committee of Copenhagen (\u201cDe Videnskabsetiske Komiteer i Region Hovedstaden\u201d) approved the project, and all subjects and/or their parents provided written, informed consent .In this cross-sectional, single-center study, healthy children and adolescents aged between 5 and 17 years were recruited from December 2011 to August 2012 from a private combined elementary and high school in Copenhagen, a public elementary school in rural Denmark, and among the healthy siblings of patients, and the children of staff at the Danish Pediatric Pulmonary Service. Prior to participation, the children (>15 years) or their parents were asked to fill out a health questionnaire covering gestational age, previous or current pulmonary disease, atopic illness, allergies, and any additional diseases the child had had, as well as current and previous medications.1/FVC below the age- and weight-specific lower limit according to recent data All participants were non-smokers, had two parents of European descent, and had no current pulmonary or cardiac disease, including any upper or lower respiratory infection 2 weeks prior to the measurements. Any use of bronchodilators, and in particular, use in the day previous to participation, was considered an exclusion criterion. Furthermore, we excluded participants with FEVHeight and weight were measured without shoes to the nearest 0.1 cm and 100 grams, respectively, using standard stadiometers and scales. Age was calculated by difference between date of birth and participation date, and was recorded to decimal accuracy.L,COHemoglobin concentration was measured by a finger stick blood sample test in all participants unless the child refused. Correction for hemoglobin concentration is not imperative in healthy children, as variations within the normal range do not significantly affect DL,CO,NO,5s, and DL,CO,10s were performed using the Jaeger Masterscreen PFT pro . Two identical sets of equipment were used at the three locations: one was used at the two participating schools and the other at the Danish Pediatric Pulmonary Service. Two experienced technicians performed all of the measurements. For most participants, spirometry and measurements of diffusing capacity were performed in a single sitting, but occasionally it required two sittings due to weariness with decreasing ability to perform technically acceptable measurements, especially with the younger children. If a participant was not able to make technically acceptable measurements in all three pulmonary function tests during the first sitting, they were invited back a second time. Spirometry always preceded the diffusing capacity measurements; DL,CO,NO,5s and DL,CO,10s were performed in a random order except in the youngest children, in whom DL,CO,NO,5s was measured first because it was the primary goal of this study.Spirometry, DParticipants breathed through a single-use mouthpiece with a built-in bacterial/viral filter connected to the pneumotachograph.L,CO,NO,5s and DL,CO,10s are performed with a identical respiratory maneuver, with the exception of breath-hold time, but it is important to clarify that they are two distinctly separate methods, contained within one equipment setup, with differences in test gasses, gas analyzers and sampling techniques.Participants were instructed to breathe normally. Following two to three normal breaths, participants performed a deep expiration and then a complete and fast inspiration. Following a breath-hold, a complete and smooth expiration was performed. As stated in the introduction DL,CO,NO,5s, and DL,CO,10s.See Quality control was performed separately for the two methods. Having unacceptable measurements for one method did not exclude the participant from attempting to perform the other method. The average of two acceptable tests for each method was reported and included in data analysis.L,CO,NO,5s and DL,CO,10s. For children with a VC <1.5 L we reduced the discard volume to 500 ml We required at least 4 minutes between each measurement, to allow adequate elimination of the test gases. Discard and sample volume were each 600 ml in both DL,CO,NO,5s and DL,CO,10sBreath-holding time was calculated using the Jones and Mead method for both DL,CO,NO,5s and DL,CO,10s was 130 ml, and the anatomical dead space was calculated according to Cotes formula from 1993 as VD, an\u200a=\u200a2.2 ml/kg The instrument dead space for both DA) was calculated using the following formula:gas is the inspiratory fraction of inert gas and FAgas is the alveolar fraction of inert gas. VIN is the inspiratory volume.Alveolar volume were corrected for hemoglobin concentration when available. DL,NO and the diffusing capacity for NO per unit of VA were not corrected for hemoglobin concentration All measurements were performed at sea level. DL,CO,NO5s and DL,CO,10s were performed according to current ATS/ERS guidelines IN/FVC) >80% as sufficient, in contrast to a ratio >85%. The vital capacity (VC) was not measured in our subjects, but FVC acquired during spirometry was assumed to be equivalent to the VC, as FVC has been shown to not differ significantly from VC in healthy subjects DL,CO,10s and DL,CO,NO,5s result in the measurement of DL,CO, VA, and KCO. In addition, DL,CO,NO,5s produces measurements of DL,NO, KNO, and allows calculation of Dm, Vc, and DL,NO/DL,CO(5s). To differentiate between the two methods, DL,CO,10s outcomes are denoted with \u201c10s\u201d and DL,CO,NO,5s outcomes with \u201c5s\u201d in this paper, e.g., VA,10s for VA measured using DL,CO,10s.Both DL,CO,10s method before start of the study and after completion of the study in both sets of equipment, and were found in accordance with ATS/ERS standards. A quality control report on both sets of equipment is provided in Supporting Information. Biological quality control of measurements using both DL,CO,10s and DL,CO,NO,5s in addition to assessments of volumes demonstrated high levels of repeatability within subjects, between session and between equipment setups during the entire study period.Volume and gas calibration and biological quality control was performed daily prior to the measurements. Calibration syringes were tested for volume accuracy and were in accordance with ATS/ERS standards \u0398CO value at pH 7.4 was used 2 was set at 100 mmHg. Using the standard hemoglobin concentrations, 1/\u0398CO was found to be 1.71 for females and for males <15 years of age, and 1.86 for males >15 years of age.Roughton and Forsters' 1/NO/DmCO ratio (\u03b1) of 1.97 \u0398NO. Recently a finite value of \u0398NO has been accepted as more accurate, and was therefore used in this study. The finite value of \u0398NO leads to the following equations:A DmL,CO,NO,5s were considered to be DL,CO,5s, KCO,5s, VA,5s, DL,NO, KNO, and the calculated outcomes DL,NO/DL,CO,5s, and Vc, Dm for the finite value of \u0398NO. Primary outcomes for DL,CO,10s were DL,CO,10s, KCO,10s, and VA,10s. Reference equations were established using Generalized Additive Models for Location Scale and Shape (GAMLSS) with extended capabilities compared to the simpler, generalized linear models. The GAMLSS regression analysis allows the median or mean value (mu), the variability (sigma), and the skewness (nu) of the outcome variable to change with the explanatory variables. Possible distributions for the GAMLSS models were normal distribution (linear regression with mu and sigma), gamma distribution (mu and sigma), or the Box-Cox Cole and Green (BCCG) distribution . The latter is suitable for skewed data.The primary outcomes for Dmu, sigma, and nu were age, sex, height, and cube of height, as well as any two-way interaction between these variables for mu. Goodness of fit was assessed by \u2018worm plots\u2019 and Q statistics IN/FVC between 80% and 85%) were included after evaluating the influence and leverage of the resulting data points in ordinary linear regression analysis http://www.r-project.org) including the GAMLSS package.Stepwise model selection was carried out using the Generalized Akaike Information Criterion (GAIC). Possible explanatory variables in the selection of Figure S1 for the age distribution.See L,CO,10s was evaluated using a paired t-test (p\u200a=\u200a0.62) and a Bland-Altman plot (mean difference\u200a=\u200a0.06). See Conformity between the two sets of equipment for DReference equations, as well as the sigma for all outcomes, are presented in L,CO,5s,, KCO,5s, DLCO,10s, KCO,10s, and DL,NO/DL,CO,5s, reference equations were produced for both hemoglobin-corrected and non-corrected values. Vc and Dm were calculated based on the finite value of \u0398NO.For DExample of calculation:L,CO,5s is:L,CO,5s of:The reference equation for DL,NO/DL,CO,5s ratio as a function of height, we saw that the ratio increased with height for the youngest participants and reached a plateau around age 14 , DL,CO,10s, and VIN,10s. Including the mean of two measurements, not complying with ATS/ERS guidelines did not alter the reference equations .Young children were less likely to meet the guideline requiring less than 10% variation between two measurements of DIN/FVC between 80% and 85% should be excluded .Using the same procedure as described for the repeatability of measurements, we found little evidence that observations of VL,CO,5s and DL,CO,10s, as the resulting data points were not highly influential, and excluding them did not alter the Z-scores. Therefore, including them in the data analysis was acceptable.The influence of a given data point, such as an outlier, cannot be evaluated using residuals or Z-scores, as highly influential points will force the regression line close to it, resulting in a small residual and Z-score. We found little evidence that participants who deviated from ATS/ERS guidelines should be excluded from the estimation of reference equations for DL,CO,10s was significantly higher than DL,CO,5s (paired t-test p<0.0001) but as expected, DL,CO,10s and DL,CO,5s were strongly correlated . Similarly, using the Passing Bablok regression, we found a systematic difference, as well as a proportional difference reflects both Dm and \u0398COL,CO primarily reflects Vc. With increasing height DL,NO will increase relatively more than DL,CO leading to the DL,NO/DL,CO,5s reaching a plateau around 140 cm.We have shown that both Vc and Dm increase with height and 9. AL,NO/DL,CO,5s in younger and smaller children may be due to a greater rate of capillary growth compared to lung surface growth or to a relatively thicker membrane in the young. As height increases with age, a compensatory relatively larger increase in Dm would result in an increasing ratio. Alveolarization has been shown to continue through out childhood and adolescence L,NO/DL,CO,5s ratio.The lower DL,CO,10s were slightly higher than existing, published reference values. One possible reason for this difference is that the present study population included children with both parents of European descent, whereas Koopman et al. included children with only one parent of European descent L in adults are small, but well established The reference values calculated in the present study for DOur results stress the importance of creating reference equations specific for a single population, or at least validating existing reference equations prior to implementing them in a laboratory setting.L,CO,10s was to secure a meaningful correlation to the much more scarcely described DL,CO,NO,5s technique, we secondarily wished to compare DL,CO measured by the two techniques. As expected we found a significant, systematic difference between DL,CO,5s and DL,CO,10s. The difference in DL,CO can be caused by a number of factors, as the two methods vary in a number of ways. See A and a resulting difference in DL,CO as DLCO\u200a=\u200aKCOA. Second, the sample method varies, with a physical gas sample being collected in the case of DL,CO,NO,5s, whereas a virtual sample was constructed from flow and gas concentration signals in the case of DL,CO,10s. Finally, we speculate if the difference in the kinetics of NO and CO in binding with hemoglobin may play a roll.Although the primary purpose of measuring DL,CO,10s focusing on varying breath-hold times, keeping all other factors constant, have shown that breath-hold time alone, influences KCO, leading to a decreased DL,CO with an increased breath-hold time L,CO.Older studies on DL,CO measured using DL,CO,NO,5s and DL,CO,10s cannot be used interchangeably for monitoring pulmonary disease. More research is required to determine how the mentioned factors combine to influence DL,CO. A given value of DL,CO can only be evaluated using reference equations produced with the same methodology and breath-hold time as recently confirmed In summary, the two methods vary in a number of ways and DL,CO,NO,5s and DL,CO,10s, resulting in a maximum of 12 tests in a single sitting. Repeating measurements of DL,CO,10s leads to an accumulation of CO in the blood, creating CO backpressure and decreasing DL,CO. However, recent work by Zavorsky showed that up to 12 tests can be performed in adults without significantly lowering the DL,CO. Furthermore, in regards to DL,CO,NO,5s, up to 22 repetitions does not lead to a decrease in DL,NOThe participants performed two or three tests, and rarely up to six repetitions of both DMeasuring lung function in this age group requires extra time and effort, but it is feasible. Most of the young children were able to perform the measurements according to ATS/ERS guidelines, but some had greater variability between measurements than normally accepted. This difference was partially due to the limited attention span of the children, who were not always able to perform repeated tests if the first two measurements did not comply with the ATS/ERS standard of a maximum 10% difference between measurements. We included measurements with greater variability, as they did not affect the estimated reference equations. Accepting greater variation in children makes sense if the alternative is to discard measurements completely.IN/VC \u226785% for adults. The recommendation is based on DLCO10s measured in a large group of adults, where 72%, 86%, and 92% of the participants were able to achieve a VIN/VC ratio of 90%, 85%, and 80%, respectively. Therefore, the recommended ratio, i.e., 85%, is a relatively arbitrary value and the guidelines state that VIN/VC <85% may still have clinical utility The ATS/ERS guidelines recommend an acceptance criterion of VAlthough most of our participants were able to inhale to more than 85% of FVC, some were not, despite multiple attempts and prompting and otherwise performing an adequate maneuver.IN/FVC >80% and reference equations only including VIN/FVC >85%.We found no differences between reference equations including measurements with VL,CO,NO,5s and DL,CO,10s would be relevant.In summary, we accepted measurements that did not meet ATS/ERS quality criteria because these measurements had no effect on the resulting equations. In the future, specific pediatric guidelines for both DL,CO,10s corresponded well to recently published equations, in particular those of Koopmans et al. The primary strength of this study is the large and acceptable age distribution of healthy children and adolescents from varying demographic backgrounds. Furthermore, this study was completed in two laboratory setups with identical equipment, as described in the online supplement. The same two technicians performed all measurements, resulting in a high level of repeatability and a systematic approach. In addition, we included children as young as 5 years of age, expanding our ability to adequately evaluate advanced pulmonary function in this age group. Finally, our calculated reference equations for DIn hindsight, it would have been beneficial to include a \u201cyoung adult\u201d group, 18\u201322 years old, in this study, as it would open up the possibility of bridging reference equations to include children, adolescents, young adults, and adults.L,CO. These include the steady state method, particularly suitable for infants or anaesthetized patients, or the rebreathing and intrabreath method, that both require cooperation, but can be performed in patients with lower lung volumes L,CO,NO.For the youngest children with a VC<1.5 liters, we reduced the discard volume to 500 ml. If the VC is even lower, as in the case of disease, this method may not be suitable. Multiple other techniques exist for DL,CO,5s, DL,NO, and the calculated outcomes DL,NO/DL,CO,5s, Vc, and Dm measured by DL,CO,NO,5s in healthy children and adults, of European descent. These equations are based on a large population with a broad age range, including children as young as 5 years of age. We expect that the present reference equations can be applied to similar populations throughout Europe, Australia and North America.This study is the first to create pediatric reference equations for the outcomes DL,NO/DL,CO,5s will lead to improved diagnostic evaluation and provide a monitoring tool for the treatment of children presenting with diffuse interstitial lung disease, whether it is a pure alveolocapillary membrane disturbance or pulmonary micro vascular disease. In particular, we believe that the DL,NO/DL,CO,5s ratio has great potential, as it is independent of the assumptions and models used to calculate Vc and Dm, that may be easily questionable. However, the clinical utility of Vc, Dm, and DL,NO/DL,CO,5s still needs to be evaluated in future studies. We acknowledge that multicenter studies are required for external validation of these results. We invite researchers to compare their results, in children with well known pathological features of the lung, with the results of this study. This will achieve increased understanding of the physiological meaning of the described measurements and their application in the early detection and monitoring of diseases.We hope that having reliable reference equations for Dm, Vc, and DFigure S1Age and gender distribution of participants.(TIFF)Click here for additional data file.Figure S2Quality control. Participants with more than 10% difference between two independent measurements of DL,CO,5s were evaluated, as this is in contrast to ATS/ERS guidelines.(TIFF)Click here for additional data file.Figure S3Quality control. Participants with more than 10% difference between two independent measurements of inspiratory volume were evaluated, as this is in contrast to ATS/ERS guidelines.(TIFF)Click here for additional data file.Figure S4Quality control. Participants with more than 10% difference between two independent measurements of DL,CO,10s were evaluated, as this is in contrast to ATS/ERS guidelines.(TIFF)Click here for additional data file.Figure S5Quality control. Participants with more than 10% difference between two independent measurements of inspiratory volume VIN,10s were evaluated, as this is in contrast to ATS/ERS guidelines.(TIFF)Click here for additional data file.Figure S6Quality control. Measurements of VIN,5s/FVC between 80% and 85% were evaluated as ATS/ERS requires values >85%.(TIFF)Click here for additional data file.Figure S7Quality control. Measurements of VIN,10s/FVC between 80% and 85% were evaluated as ATS/ERS requires values >85%.(TIFF)Click here for additional data file.Appendix S1Age distribution.(DOCX)Click here for additional data file.Appendix S2Excel worksheet.(XLSX)Click here for additional data file."} +{"text": "Contributions\u201d series, dedicated to disseminating systematics research on the Noctuoidea, Geometroidea, and other macro-moth groups. Previous volumes were published in May 2009 , March 2010 , November 2011 , February 2013 and June 2014 , two species from the western United States , and two new genera . All updates and corrections to the Check List of North American Noctuoidea (In the current volume, eight authors contributed six manuscripts on North American taxa in the ctuoidea since th"} +{"text": "Each day, on average, two construction workers die in the United States . In 2010CDC\u2019s National Institute for Occupational Safety and Health has engaged the construction sector through a government/labor/management partnership, representing state and federal government agencies, professional organizations, trade associations, labor organizations, and private industry. The goal, in part, is to develop a national campaign aimed at construction contractors, onsite supervisors, and workers to address and reduce falls, fall-related injuries, and fall-related fatalities among construction workers. On Workers\u2019 Memorial Day, April 28, 2013, a national information and media campaign will be launched again through this partnership."} +{"text": "The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened a Working Group on the Microbiome in Cardiovascular, Pulmonary and Hematologic Health and Diseases from June 25, 2014, to June 26, 2014. The Working Group\u2019s central goal was to define what major microbiome research areas warranted additional study in the context of heart, lung, and blood (HLB) diseases. The Working Group identified studies of the human virome a key priority. FindIn addition to the outcome of the Working Group described above, the NHLBI Strategic Visioning, an ongoing process dedicated to shape scientific priorities for the Institute and guide future funding strategies over the next decade, identified virome research as an area for further focus. To help address this need, NHLBI developed an initiative to support studies that evaluate how the human virome interacts with its host and the molecular and physiological mechanisms that govern those interactions. The funding opportunity announcement (FOA), RFA-HL-17-002, entitled, \u201cThe Role of the Human Virome in Heart, Lung, and Blood Health and Resilience (R61/R33),\u201d was published on October 5, 2016, with the receipt date of June 24, 2016, or for AIDS Applications: August 9, 2016, and will award grants in fiscal year 2017 . It is hAIDS, acquired immunodeficiency syndrome; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; FOA, funding opportunity announcement; HBV, hepatitis B virus; HGV, hepatitis G virus; HIV, human immunodeficiency virus; HLB, heart, lung, and blood; HMP, the NIH Human Microbiome Project; HSC, hematopoietic stem cell; HSCT, hematopoietic stem cell transplantation; IBD, inflammatory bowel disease; NHLBI, National Heart, Lung, and Blood Institute; NIH, National Institutes of Health"} +{"text": "In the last few decades, health systems research (HSR) has garnered much attention with a rapid increase in the related literature. This study aims to review and evaluate the global progress in HSR and assess the current quantitative trends.Based on data from the Web of Science database, scientometric methods and knowledge visualization techniques were applied to evaluate global scientific production and develop trends of HSR from 1900 to 2012.HSR has increased rapidly over the past 20 years. Currently, there are 28,787 research articles published in 3,674 journals that are listed in 140 Web of Science subject categories. The research in this field has mainly focused on public, environmental and occupational health , health care sciences and services , and general and internal medicine . The top 10 journals had published 2,969 (10.31%) articles and received 5,229 local citations and 40,271 global citations. The top 20 authors together contributed 628 papers, which accounted for a 2.18% share in the cumulative worldwide publications. The most productive author was McKee, from the London School of Hygiene & Tropical Medicine, with 48 articles. In addition, USA and American institutions ranked the first in health system research productivity, with high citation times, followed by the UK and Canada.HSR is an interdisciplinary area. Organization for Economic Co-operation and Development countries showed they are the leading nations in HSR. Meanwhile, American and Canadian institutions and the World Health Organization play a dominant role in the production, collaboration, and citation of high quality articles. Moreover, health policy and analysis research, health systems and sub-systems research, healthcare and services research, health, epidemiology and economics of communicable and non-communicable diseases, primary care research, health economics and health costs, and pharmacy of hospital have been identified as the mainstream topics in HSR fields. These findings will provide evidence of the current status and trends in HSR all over the world, as well as clues to the impact of this popular topic; thus, helping scientific researchers and policy makers understand the panorama of HSR and predict the dynamic directions of research. With the approach of 2015, many countries intend to hasten their efforts towards meeting the Millennium Development Goals (MDGs), and meanwhile they have already began discussing the post-MDGs health roadmap . Well-fuall organizations, people and actions whose primary intent is to promote, restore or maintain health\u201d [Health systems have existed in some form for over 100 years, when individuals and eventually governments became interested in organizing health systems to protect their population\u2019s health and treat their diseases . However health\u201d . This de health\u201d . The WHO health\u201d ,7. There health\u201d . It is t health\u201d . The \u201cso health\u201d . As such health\u201d ,8.The current surge in activities and researches around health systems is encouraging. Funding has increased in recent years ,11 with Role and Promise of Policy and Systems Research[Sound Choices: Enhancing Capacity for Evidence Informed Health Policy[Systems Thinking for Health Systems Strengthening[HPSR: A Methodology Reader[PLoS Medicine commissioned three articles on the state-of-the-art in HSR [Recent studies also have called for intensified investment, methods development, and capacity building in the assessment and research that accompanies health systems investment, ultimately strengthening the implementation processes. AHPSR have published the Research, Sound Cth Policy, Systemsngthening, and mosgy Reader in ordert in HSR ,18,19. Tt in HSR . The most in HSR ,20.Overall, high level meetings and community level advocacy groups have highlighted the challenges that lie ahead: the post-MDGs global health agenda, burgeoning non-communicable diseases, achieving universal health coverage, and strengthening fragile health systems in low- and middle-income countries . TherefoThe main purpose of this study is to evaluate the global progress and quantitatively assess the current research trends on HSR. A comprehensive scientometric analysis and substantial discussion of research progress in HSR were provided so that specific attempts were employed in order to i) summarize significant publication patterns in HSR with basic statistics as well as advanced analysis, ii) evaluate research performance from multiple perspectives such as year of publication, subject category, journals, countries/regions, and institutes as well as authors ,23, and As a strictly selected abstract database, Web of Science (WoS), including Science Citation Index Expanded, Social Sciences Citation Index, and Arts and Humanities Citation Index, has long been recognized as the most authoritative scientific and technical literature indexing tool providing data on the most important areas in science and technology research, especially about medicine. Furthermore, the WoS database includes the world\u2019s most important journals in relation to healthcare science, health policy, and systems research. The majority of high quality articles on healthcare science research are indexed by WoS. In addition, as a citation database, WoS provides enough search fields, such as keywords, country, organization, author, and references, which are all very important for literature analysis, especially for scientometric analysis ,25. TherFollowing the best international practices, \u2018evaluative scientometrics\u2019 was selected for this study. Scientometrics is a method by which the state of science and technology can be observed through the overall production of scientific literature at a given level of specialization. This tool provides an approach for situating a country in relation to the world, an institution in relation to a country, and individual scientists in relation to their peers. Scientometric indicators are equally suitable for macro-analysis and micro-studies . In thisThe term \u2018co-author\u2019 is used to denote the appearance of multiple writers simultaneously in one paper, and also reflects the collaboration of different institutes, regions, or countries ,34. The There were 35,819 total HSR-related papers in the Science Citation Index Expanded, Social Sciences Citation Index, and Arts and Humanities Citation Index databases used for this study, distributed over 17 different document types . There wThe publication trends in annual papers in HSR from 1981 to 2012 are shown in Figure\u00a0Based on the classification of subject categories in the Journal Citation Report of WoS, the publication output data of HSR during the last century was distributed in 140 subject categories. The top 10 productive subject categories are shown in Table\u00a0HSR was mainly located in the fields of public, environmental and occupational health, health care sciences and services, and general internal medicine as shown in Table\u00a0Thomson Reuters\u2019 WoS covers research published in more than 12,000 scientific journals and conference proceedings, and is presently one of the most extensive sources of research and development outputs. HSR output was published in 3,674 journals, where the top 10 journals with more than 200 articles are displayed in Table\u00a0Social Science & Medicine, Health Policy, and Health Affairs. Health Affairs ranked first both in quantity and quality with the highest TLCS, TLCS/t, TGCS, TGCS/t, AGCS, impact factor, and H-index, followed by Social Science & Medicine. Moreover, Health Policy ranked third both in TLCS and TGCS, while Health Policy and Planning had a relative high TLCS/t and TGCS/t. In addition, Medical Care has a high AGCS and impact factor, which reflects the high quality of articles published in it. Since Social Science & Medicine, Health Policy, Health Affairs, and Medical Care published health systems-related papers in the early stages, they constitute the most important journals during the development process of HSR of articles among the 11 most frequently cited articles, which also exhibited its predominance. In addition, among the top 11 cited papers, USA contributed to 7 and Switzerland 3 articles, respectively, and Brazil, a developing country and an \u2018emerging economy\u2019, held 1. The WHO published 3 articles and ranked first among all institutions, which reflects its dominant position in the HSR from 1900 to 2012 are listed in Table\u00a0SR Table\u00a0.To locate the most popular research topics and their trends, the distribution of authors\u2019 keywords and keywords-plus was investigated. As for author keywords analysis, they offer information about research trends from the view of researchers, and they have proved to be important in monitoring the development of science . KeywordExamination of author keywords in this study period revealed that, altogether, 29,480 author keywords were used, among which 21,658 (73.47%) keywords appeared only once, and 3,188 (10.81%) keywords appeared twice. The high percentage of only once author\u2019s keywords probably indicated to the lack of continuity in research and a wide disparity in research focus. Another reason was that these keywords might not be standard or widely accepted by researchers. Author keywords appearing in articles that refer to HSR were calculated, and the top 60 author keywords were used and clustered with VOSviewer from 1900 to 2012 includes health policy and analysis research such as policy design and implementation -50, chalGroup 2 (green) includes epidemiology and economics of communicable diseases, such as HIV, tuberculosis, and malaria, and non-communicable diseases, such as hypertension, diabetes, cancer, obesity, global diseases ,21,97, eGroup 3 (yellow) includes primary care research, training and education -100, quaGroup 4 (blue) includes health economics and health costs, health expenditure control ,113, heaAs supplies of author keywords, we also examined the co-occurrence relationships among the top 60 high frequency keywords-plus and the co-word networks were visualized using VOSviewer Figure\u00a0. With thSocial Science and Medicine, Health Policy, Health Affairs, and BMC Health Services Research. Hence, these journals are the core journals and play important roles during the knowledge dissemination and exchange in HSR.In this study, we have provided a supplemental evaluation of the status of HSR. Our analysis confirms that papers in HSR have increased rapidly during the last 20 years, and most notably in the last 8 years. In total, there were 28,787 research articles published in 3,674 journals listed in 140 SCI subject categories. Research in the fields of HSR have mainly focused on public, environmental and occupational health, health care sciences and services, and general and internal medicine. All output has been concentrated in several journals such as The HSR output is distributed unevenly by countries, institutes, and authors. OECD countries, especially the G7 countries, have published the majority of articles. In addition, USA, UK, and Canada stand in the core of international collaborative networks. Thus, they promote the creation, transmission, and sharing of knowledge in HSR fields. China, a developing country, also plays an important role in the country\u2019s collaborative network category. Furthermore, American and Canadian institutions, and the WHO have made great advances in paper research production, citation, and cooperation, along with the overall great strengths and good development prospects. Meanwhile, the most frequently cited articles come from the USA and Switzerland, during which American-authored papers had contributed the most to this field. Brazil, a developing country and as an emerging economy, also held one. The WHO published three articles and ranked first among all institutions, reflecting its dominant position in the HSR. McKee M, from the London School of Hygiene & Tropical Medicine published the most articles. However, most of the productive authors are from American institutes, such as University of Michigan. Finally, it could be concluded that the USA and its universities and academic institutions play a dominant role in the production, collaboration, citation, and high quality of articles.HSR is an interdisciplinary area and includes medicine, public-environmental and occupational health, health care sciences and services, pharmacology and pharmacy, economics, sociology, information science and technology, and psychology. Whilst health economics is a central discipline of HSR, the analyses most centrally fell within HSR, including work that focuses on financing. Its current hotspots center on health policy and analysis research, health systems and sub-systems research, healthcare and services research, epidemiology/economics of communicable and non-communicable global diseases, primary care research, health economics and health costs, pharmacy of hospital, and health . Meanwhile, the main topics found from the analysis of keywords-plus are in accordance with authors\u2019 keywords analysis results. Further, \u2018meta-analysis\u2019, \u2018randomized controlled-trial\u2019, \u2018disorders\u2019, \u2018schizophrenia\u2019, \u2018United States\u2019 \u2018physicians\u2019, and \u2018women\u2019, which were not in the top author keywords map, but also had significant roles in the keywords-plus map. Hence, these topics are also hot topics in HSR. Furthermore, from the perspective of citation, most researchers that have studied health systems have concentrated on the topics of health outcomes , responsiveness to health systems , leadership and governance , health financing and health expenditure , health services and quality of care , health performance assessment , health information systems , and health workforce. In addition, more and more attention has been paid to the developing countries, especially the \u2018emerging economies\u2019 (such as Brazil and China).These findings will provide evidence of the current status and trends in HSR all over the world, as well as clues to the impact of this popular topic, thus helping scientific researchers understand the panorama of HSR, and predict the dynamic directions of research. Therefore, based on these findings, policy makers could understand the status and positions of their countries or institutions, and the directions of HSR all over the world. Thus, they could spell out suggestions for HSR or reform directions. For example, they could develop post-MDG global health agendas, set health systems priorities areas, strengthen fragile blocks of health systems, and learn successful lessons from abroad to achieve universal health coverage. Meanwhile, the process of developing an HSR study begins with identifying the topic of focus \u2013 the issue or problem you want to investigate \u2013 and the related questions. Hence, with the help of these findings, researchers could select their research directions or topics, cooperative institutions and partners, and even choose academic achievements\u2019 platform exchange. In addition, because HSR is defined by the topics and the questions it addresses rather than the disciplinary perspective or the particular approach to data collection and analysis it adopts, the distribution of research subjects and hot topics will help people to understand the concepts of health systems.The results presented herein can provide evidence about the current status and future trends in HSR, as well as clues to the impact of this hot topic. However, they could not present the research foci of HSR simultaneously from multiple angles. For example, we could not clearly present the research features of journals, countries, institutions, or authors in one knowledge map. Further, we could not show the evolution pathway of HSR from different angles, such as the topic changes with time. Thus, future efforts are needed to describe the features of journals, countries, institutes, and authors, specifically the performance changes of processes in health systems areas.AGCS: average global citation score; AHPSR: Alliance for Health Policy and Systems Research; HSR: Health Systems Research; MDGs: Millennium Development Goals; OECD: Organization for Economic Co-operation and Development; TGCS: total global citation score; TLCS: total local citation score; WHO: World Health Organization\u2019s; WoS: Web of Science.The authors declare that they have no competing interests.LY initiated and designed the study, she also obtained the funding. QY, PHL and ZYL were involved in the data collection and analysis. QY participated in the study design, collected the data, and conducted the data analysis and the writing of the manuscript. PHL contributed to the design and analysis of the data and prepared the manuscript. ZYL contributed to the data analysis and revision of the manuscript. KC, FL, SQC, LYH and TAY edited the paper. All authors were involved in the interpretation of data and have read and given final approval of this paper.Annex S1.Click here for file"} +{"text": "Africa's population is growing at the fastest rate and it is estimated that by 2100, 38.5% of the 10.9 billion humans will be leaving in Africa. .The optimal health of a community is a result of a dynamic and fragile equilibrium among several elements such as: health determinants, human competencies, leadership, governance, health system, health delivery, policy and legislation . The cur"} +{"text": "We regret any inconvenience or confusion this error may have caused.In the article \u201cEffectiveness of Fresh to You, a Discount Fresh Fruit and Vegetable Market in Low-Income Neighborhoods, on Children\u2019s Fruit and Vegetable Consumption, Rhode Island, 2010\u20132011,\u201d we inadvertently listed an author affiliation for Sara Gorham incorrectly. Ms. Gorham is affiliated with the Institute for Community Health Promotion, Brown University School of Public Health, Providence, Rhode Island. The changes were made to our website on October 16, 2015, and appear online at"} +{"text": "A brief summary of the early history of the study of Atlantic Ocean marine fish digeneans is followed by a discussion of the occurrence and distribution of these worms in the Atlantic Ocean and adjacent Eastern Pacific Ocean, using the Provinces of the \u2018Marine Ecoregions\u2019 delimited by Spalding et al. (Bioscience 57:573\u2013583, Fasciola ventricosa Pallas 1774, now recognised as Hirudinella ventricosa Baird, 1853, a large stomach parasite of large scombrid fishes originally reported from Ambon Island, Indonesia but now reported worldwide Looss, 1901, originally reported from Danish waters Nicoll, 1909, Macvicaria soleae Gibson & Bray, 1982 and Podocotyle angulata Dujardin, 1845 off the Brittany coast, France. Other early workers in the north-eastern Atlantic include Thomas Spencer Cobbold Stafford, 1904, presumably from a haddock apparently examined at Edinburgh, Scotland. Peter Olsson described many worms from the Scandinavian coasts Odhner, 1905, Zoogonoides viviparus Odhner, 1902, Zoogonus rubellus Odhner, 1902 and Fellodistomum fellis Nicoll, 1909. \u00c9douard van Beneden illustrated some worms from the Belgian coast Odhner, 1911 and Otodistomum cestoides Stafford, 1904.The study of the marine trematode fauna of the world can be said to have started in the Atlantic Ocean basin, although the earliest recognisable post-Linnaean name to be coined for a marine digenean is probably Pallas, . Other e M\u00fcller, consider M\u00fcller, describe Cobbold who descDistomum lasium, from off New Jersey, USA, which is now recognised as Zoogonus lasius Stunkard, 1940. Edwin Linton started describing digeneans from various localities off the North American coast in the late 19th Century Bartoli, Bray & Gibson, 1989, Opechona pyriforme Bray & Gibson, 1990, Opecoeloides vitellosus von Wicklen, 1946, Prosorhynchoides arcuatus Love & Moser, 1983 and Lintonium vibex Stunkard & Nigrelli, 1930.Little was done in the Western or Southern Atlantic during the 19th Century. Joseph Leidy describeLecithaster confusus Odhner, 1905, Hemiurus levinseni Odhner, 1905, Aporocotyle simplex Odhner, 1900, Prosorhynchus aculeatus Odhner, 1905, Hemiurus communis Odhner, 1905, Proctophantastes abyssorum Odhner, 1911 and many more. Other north-eastern Atlantic workers of the early 20th Century are the British workers William Nicoll and Marie Lebour, whose contributions include the recognised species Fellodistomum agnotum Nicoll, 1909, Peracreadium idoneum Gibson & Bray, 1982, Diphterostomum vividum Bray & Gibson, 1986, Lepidapedon elongatum Nicoll, 1910 and Steringotrema ovacutum Yamaguti, 1953.Modern generic concepts began to be developed in the early 20th Century by Max L\u00fche and Arthur Looss in the Mediterranean and Teodor Odhner in the Atlantic. An important early work by the latter on Arctic worms Odhner, , was oneHomalometron pallidum Stafford, 1904, Neophasis pusilla Stafford, 1904, Stenakron vetustum Stafford, 1904 and Steganoderma formosum Stafford, 1904, is due to the restudy of Stafford\u2019s material by Max Miller Overstreet, 1969, Genolopa elongata Manter, 1931, Genolopa minuta Manter, 1931, Proctotrema lintoni Manter, 1931 and Prodistomum menidiae Bray & Gibson, 1990.No summary of the early work in the Atlantic Ocean would be complete without a mention of the contribution of Harold Manter. Starting in 1925 Odhner, 1911, Stephanostomum dentatum Manter, 1940, Opechona pyriforme, Lintonium vibex, Lepocreadium areolatum Stunkard, 1969, Tubulovesicula pinguis Manter, 1947, Lasiotocus minutus Thomas, 1959, Neopechona cablei Stunkard, 1980 and others Dollfus, 1927, Zoogonoides viviparus, Stephanostomum caducum (Looss 1901) Manter, 1934, Monascus filiformis Looss, 1907, Steringophorus furciger Odhner, 1905, Derogenes varicus, Steringotrema pagelli, Fellodistomum fellis, Podocotyle reflexa Odhner, 1905, Aporocotyle simplex, Lepidapedon elongatum, Lecithaster gibbosus L\u00fche, 1901, Lecithochirium rufoviride L\u00fche, 1901, Hemiurus luehei Odhner, 1905, Lecithocladium excisum L\u00fche, 1901, Magnibursatus caudofilamentosa Gibson & K\u00f8ie, 1991, Brachyphallus crenatus Odhner, 1905 and Hemiurus communis Odhner, 1905 and his students, who have used the literature to write over 25,000 lines. The Atlantic and Eastern Pacific Ocean records from this database have been extracted and some further records have been added (by RAB and PED). The locality records have been coded according to Provinces of the \u2018Marine Ecoregions\u2019 delimited by Spalding et al. see Tab, Fig. 1AConsidering the number of records accumulated, it might be considered that we know a good proportion of the fauna, but the effort in different parts of the Ocean has certainly not been even.The following data relating to the 17 regions of the Atlantic Ocean have been collated, along with the five Eastern Pacific regions: the number of species, genera and families in each region, the number of lines in the database per species, genus and family. These latter three parameters give an estimate of the effort in each region Table\u00a0. The numAs can be seen, the Tropical Northwest Atlantic (12) has the most described species, followed by the Mediterranean Sea (4). In terms of lines per taxon, the Northern European Seas Province (2) is the most studied region, but the Arctic (1), Mediterranean Sea (4) and possibly the Cold Temperate Northwest Atlantic (5) and the Tropical Northwest Atlantic (12), have very similar levels of effort. The effort in the southwestern Atlantic is considerably less and no records were recovered from the North Brazilian Shelf Province (13). The best known fauna from this region is Warm Temperate Southwestern Atlantic (47). The south-eastern Atlantic is the least studied continental coastal zone (with only two records recovered from the Benguela region \u221250). The two mid-Southern Atlantic Island provinces (15 and 49) have only one record each.The database has in total 9,880 records of 1,274 species in 430 genera and 45 families, of which 8,633 are from the Atlantic Ocean, with 1,125 species in 384 genera and 45 families. About 1,000 species are endemic to the Atlantic Ocean basin, but Lessepsian migrants and other identifications of Indo-West Pacific species confuse the picture.Lepidapedon Stafford, 1904 and other lepidapedids and fellodistomids and 65 from the Mediterranean Sea (4) and the Warm Temperate Eastern Pacific (45). Considering the relatively few records of identified species in Region 45 (39% records are of unidentified worms), it seems clear that workers in this region, particularly in Chile and Peru, have suffered from a distinct taxonomic deficiency. On the other hand, Regions 12 and 4 are the most thoroughly studied regions and the number of records of unidentified parasites is relatively low (about 3% in both regions).The number of genera and species found in the families in the Atlantic Ocean are listed in Table\u00a0The most species-rich, and jointly the most widespread, family is the Opecoelidae Ozaki, 1925\u00a0Fig.\u00a0. The thiThe Atlantic is depauperate in some families that are relatively common in the Indo-West Pacific Region: the Gyliauchenidae Fukui, 1929, Enenteridae Yamaguti, 1958, Opistholebetidae Fukui, 1929 and Bivesiculidae Yamaguti, 1934\u00a0are notable examples. Other families are seemingly missing from the Atlantic entirely, including the Transversotrematidae Witenberg, 1944\u00a0and the Atractotrematidae Yamaguti, 1939.Himasthla tensa Linton, 1940 in the Atlantic cod Gadus morhua L. must also be considered an accidental infection Odhner, 1902 and Derogenes varicus. Recent studies Lunaschi, 2003. Lecithochirium genypteri is, however, circum-austral having been originally reported in New Zealand Bray, Cribb & Barker, 1993 (Pais et al., The effect of man on the distribution of marine digeneans is exemplified by the effects of migration through the Suez Canal, so-called Lessepsian migration. We can be confident that this is changing the fauna, but to what extent it is not yet clear. For example, the herbivorous rabbit fish Our data suggest 1,125 species in 384 genera and 45 families are reported in marine fishes of the Atlantic Ocean basin; almost 1,000 of these species are endemic to the Atlantic Ocean. The geographical region which is most poorly known is the South Eastern Atlantic Ocean, with few reports and, apparently, no current research. The deep-sea of the southern part of the Atlantic Ocean is also virtually un-studied.The discovery of cryptic species in the Atlantic is in its early stages and will, without doubt, alter our understanding of the Atlantic digenean fauna as it has already in parts of the Indo-West Pacific (Miller et al.,"} +{"text": "There are errors in the Funding section and Acknowledgements section. The complete, correct Funding statement is as follows:No external funding was received for this study. Some resources (supplies and research assistance) were donated by T.S. Talley through California Sea Grant Project A/EA-AR-37, Ocean Discovery Institute, and D.M. Talley and N. Reyns through Environmental and Ocean Sciences at University of San Diego. The statements, findings, conclusions and recommendations are those of the researchers and do not necessarily reflect the views of the aforementioned organizations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The complete, correct Acknowledgements section is as follows:We are grateful to the University of California Natural Reserve System, Tijuana River National Estuarine Research Reserve, U.S. Fish and Wildlife Service, Torrey Pines State Park, Ocean Discovery Institute, as well as Mark Page, Steve Schroeter, Andres Deza, and Justin Hoestery for site access and/or use of data. Thanks to the field sampling assistance of Rosa Calvario, Marlem Rivera, Carla Pisbe, Christine Whitcraft, Larisa Chavez, Liz Lopez, Nathalie Reyns\u2019 2009\u20132011 Marine Community Ecology classes at University of San Diego, and Paul Detwiler\u2019s 2013 Marine Science class at San Diego Mesa College. We also thank Erik Thuesen and two anonymous reviewers for helpful comments that improved this manuscript."} +{"text": "One of the affiliations of Vladimir Flores was omitted in the original paper.The original paper affiliations were:Melina Rapacioli1, Ver\u00f3nica Palma2and Vladimir Flores1*1Interdisciplinary Group in Theoretical Biology, Department of Biostructural Sciences, Favaloro University, Buenos Aires, Argentina2Laboratory of Stem Cell and Developmental Biology, Faculty of Science, University of Chile, Santiago, ChileThe correct affiliations should be:Melina Rapacioli1, Ver\u00f3nica Palma2and Vladimir Flores1, 3*1Interdisciplinary Group in Theoretical Biology, Department of Biostructural Sciences, Favaloro University, Buenos Aires, Argentina2Laboratory of Stem Cell and Developmental Biology, Faculty of Science, University of Chile, Santiago, Chile3Laboratory of Developmental Neurobiology, Institute of Cell Biology and Neurosciences \u201cProf. E. De Robertis\u201d (UBA-CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, ArgentinaThe correction does not affect the scientific validity of the results.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest"} +{"text": "In the course of the millennia, fire, a natural as well as a man-made entity, has been promoting human cultural and technological development. However, just like other powerful forces, fire has two sides: one that is positive or helpful and another that is negative or harmful. Obviously, as human beings survive and prosper better with fire than without it, it follows that possible burn injuries will stay with human beings.th Meeting of the International Society for Burn Injuries (ISBI) held in Edinburgh in 2012. That proposal outlines the ideal state of affairs, and indeed it is also our dream. On the contrary, all over the globe, patients with burn wounds are at present exposed to widely dissimilar conditions stemming from broadly different ethnic cultures, personal economic conditions, national health policies, and local medical traditions, which together end up determining profound dissimilarities in burn care. This inconsistent care is the reason for us launching an open-access journal, Burns & Trauma, as we wish to share on this platform several experiences, different data, various cases, and diverse ideas in a fast and easy way. Doctors, scientists, nurses, therapists, and social workers could improve the care of burn patients, promote the prevention of fire disasters, decrease postburn disabilities, and pursue a common dream: \u201cNo Burn Injury\u201d or at least \u201cOne World, One Standard\u201d.For a number of well-known reasons, burn injury remains a quite severe social and medical problem. \u201cOne World, One Standard\u201d was the proposal as the aim of the 16Burns & Trauma is an open access journal that aims to cover the latest and best achievements in all aspects of burn and trauma research. This new journal will provide a unique platform for the rapid publication of guidelines, original articles, review articles, case reports, letters, commentaries, and thematic issues on scientific research related to burn and trauma research. Themes include but are not limited to emergency medicine, wound healing, tissue engineering, intensive care, nutrition, bioengineering, shock, rehabilitation, immunology, infection, psychology, stem cells, organ damage, injury epidemiology, regeneration, and so on.Burns & Trauma: Antonino Gullo, Zhiyong Sheng, Zhengguo Wang, Xiaobing Fu, David Mackie, Basil A. Pruitt, Ronald G. Tompkins, Yongmin Yu, Ubaldo Armato, Xianchang Li, Xuetao Pei and the whole editorial team. Their suggestions, encouragement, and hard work will promote the growth of this forthcoming journal absolutely.I wish to acknowledge the people who have enthusiastically contributed to the launch of that Burns & Trauma will act as a successful vehicle for sharing our knowledge and thereby significantly contributing to the prevention and the management of burn injuries.I sincerely hope"} +{"text": "I felt the world narrowas I looked at her, a frail womantonight thin and grey,lent animus by memory anddesperation and loneliness.She gestured weakly as I came to herand said something, muffled,under the thick, coiled tubingwhich snaked to the maskbound about her face.I took the straps off,and at this early morning hourshe straightened her hair feebly,gazing in the darknessas the machine sputtered and blew.I rapidly ministered to it,pleading for silence.Freed now, she spoke;Dimly, there arose an elegance,rapidity and lucidity,an English accent and gentle wordsspilling out in her deprecating way.She beckoned; I sat,and held her hand.She told me of her time -she was a young woman,on a boat, falling away,journeying overseas, Australia,to a new home far removed.Of a man she had met there, and loved and buried.Of her work -she had thought it very important;Of the children she had borne -how she missed them.For me, for herself,she sketched the arc of her star.Sitting on a precipice, she spoke:What really mattered now, heremostly alone, in the dark,a small hospital roomand drawn curtains, fold-out fabric walls.At times I held that blowing maskagainst her face, to give her the breath,at times I asked a question -but mostly I listenedand held her hand.The machine huffed, disconnected,waiting, in the dark.She smiled as she spoke,sometimes mocking herself,sometimes wry, sometimes happy,on some things she couldn\u2019t speak -we both understood.She held a strength, I knew,found in those who dare reject hubris.My pager interrupted,it was the world interrupting, really,I silenced it -and sat with her and listeneduntil I could no more.Her last words,said with a smile: \u201cI know you\u2019re busy.Thank you for listeningto an old windbag like me.\u201dI told her it was my pleasure -I have always honored teachers.I strapped the mask back onand smiled at her, constrained,buried now, under mask and tubingwith life and machineconnected again, far from equal.She gazed up at me, still and silent.I gave her hand a squeeze,and left into the world of light,and movement,and things to be done.My world had expanded,but it was her last conversation."} +{"text": "Scientific Reports5: Article number: 13012; 10.1038/srep13012published online: 08172015; updated: 10292015In the original version of this Article, Klaus Leifer was incorrectly listed as being affiliated with \u2018Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden\u2019. The correct affiliation is listed below:Department of Engineering Sciences, Division of Applied Materials, Uppsala University, Uppsala, Sweden.This error has now been corrected in both the HTML and PDF versions of the Article."} +{"text": "When he introduced the paradigmatic \u201clexical\u201d method of deriving personality trait terms from the dictionary, he therefore sought to exclude all trait terms with ostensive normative content. This approach had a profound effect upon the field, and researchers are still today working on how to optimally purge personality of normative content , thereby attaining \u201ccoherence\u201d of body, mind, and spirit, unconditional well-being, potential access to other minds, and \u201cdirect self-aware perception of what is real and true without misunderstanding as a result of preconceptions, prejudices, fears, desires, and conflicts\u201d (p. 325). Cloninger and the Higgs field within which particles acquire mass, and he claims, furthermore, that the unpredictability of quantum physical events is \u201canother way of talking about freedom\u201d (p. 73) and that \u201cthe thought of gifted people involves intuitive leaps or quantum jumps, not deductive algorithms\u201d cooperativeness, or communion, which incorporates compassion, empathy, helpfulness, acceptance of others, and acting on moral principles rather than self-interest, and (3) self-transcendence, which incorporates a sense of unity underlying the universe and connecting the self with the world around it, intuitive apprehension of relationships that cannot be explained rationally or observed objectively, and experiences of flow, absorption, and self-forgetfulness. These aspects of character correspond, respectively, to the person's relation to the self, to others, and to the universe. As such, they undoubtedly refer to basic aspects of our intentional engagement with the world. But the model does not take different worldviews into account. Self-transcendence, in particular, appears conflated with spiritual self-transcendence\u2014that is, self-transcendence through spirituality. Self-transcendence, in a more general sense, can be understood as the pursuit of meaning and identity through participation in, and selfless contribution to, something larger than the self, whether this is a divine or spiritual reality, a community of persons or sentient beings, or an ideological ideal (Schwartz, Cloninger et al. model dihow, different worldviews can be reconciled with ethical self-transcendence, selfless love, genuine happiness, tolerance, creativity, autonomy, and experiences of wonder, beauty, and awe. It is, I suggest, unlikely that there is one ultimate path of character development suitable for all persons. Cloninger's (More generally, I suggest that character can be understood in terms of the interaction between the three proposed dimensions and the person's worldview, and that researchers therefore need to investigate how different worldviews facilitate and inhibit the development of character. Because character is an intrinsically normative concept, what counts as character is partly an empirical question\u2014character is what turns out to produce desirable psychological, moral, and social consequences. We might ask, for example, if, and if so ninger's , p. 29 oninger's , 2013.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "RoNeuro Institute, an academic excellence research and diagnosis center for the neurological diseases, came true, managing to treat over 3000 patients, most of them representing difficult cases in Romania and abroad. The existence of not only some remarkable professionals but also the latest technologies in the field, which were used for the first time in Romania, as for example the eye-tracking system, in the process of evaluating the cognitive performances, has made possible its fully deserved assertion in the elite medical world. In less than one year, the dream of the Foundation for the Study of Nanoneuroscience and Neuroregeneration, Society for the Study of Neuroprotection and Neuroplasticity (SSNN), together with the Romanian Society of Neurology (RSN) and \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy in Cluj-Napoca, under the aegis of the European Federation of NeuroRehabilitation Societies (EFNRS) and the World Federation for NeuroRehabilitation (WFNR), the scientific and exceptional educational medical event, RoNeuro Brain Days, which hosted the 5th edition of the European Teaching Course on NeuroRehabilitation, and which took place in the period 1-4 of June 2015, in Cluj-Napoca, the location being \u201cGheorghe Marinescu\u201d Amphitheatre in \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, has managed to bring together professionals in the field of medicine and world scientific researches, from countries such as Germany, USA, Austria, Italy, Ukraine and Romania.Organized by the Prof. Dafin F. Mure\u015fanu, MD, President of the Romanian Society of Neurology (RSN) and President of the Society for the Study of Neuroprotection and Neuroplasticity (SSNN), affirmed.\u201cWe would like to develop rehabilitation in Romania in a modern, interdisciplinary context, in which the neurologist, the specialist in physical medicine and recovery medicine, the psychologist, logopedist, kinesiotherapist, ergotherapist and medical assistant work together as a team and generate the optimum result for the patient. We would also try to bring a neurorehabilitation component in the field, in the near future, a curriculum being already developed at the European level. Neurorehabilitation represents an interdisciplinary growing field in Europe. Many national societies are born under our sight, but certainly, the leaders are still the national societies in Germany, Italy, Holland, Austria. Romania is active in this field with the help of the two neurorehabilitation societies\u201d, \u201cThere are some factors and the lifestyle is the most important. Hypertension, atrial fibrillation, dyslipidemia, diabetes, physical inactivity, obesity, smoking, exaggerated alcohol or central nervous system stimulant substances consumption, intellectual overstrain, stress, hormonal dysfunctions, brain trauma, are reasons which can generate an early brain aging\u201d, Prof. Dafin F. Mure\u015fanu, MD, declared. Premature brain aging and brain regeneration have been the main preoccupations of the elite of neurologists who took part in the event in Cluj. RoNeuro Brain Days, which drew the attention to the positive effects of the treatment with neurotrophic factors in patients with this type of brain injuries. According to these data, the treatment significantly improves the patients\u2019 quality of life. In this complex study, coordinated by Prof. Dafin F. Mure\u015fanu, 25 top neurosurgeons and neurologists have taken part, mostly from Romania, who have treated and monitored 7.769 patients on a period of 5 years, in 10 neurosurgery departments in Romania. The greatest retrospective traumatic brain study in the last decade has been presented in \u201cThis study has been a real challenge for neurology in general and especially for neurosurgery. The results have shown an obvious improvement of the health state of the patients who suffer from brain injuries, which are mostly produced due to road accidents, to which the new treatment had been applied in the first 48 hours from the accident\u201d, Prof. Fafin F. Mure\u015fanu, MD, commented.RoNeuro Brain Days, another event took place, The Congress of the European Society for Clinical Neuropharmacology (ESCNP), which is one of the elite societies of world medicine, whose president elected last year, is Prof. Dafin F. Mure\u015fanu, MD. In addition, Prof. Mure\u015fanu continues the projects of his predecessor, Prof. Johannes Thome, MD, from Germany, a scientific society whose purpose is the promotion of education and acquiring a high level of knowledge and understanding in the field of clinical neuropharmacology. The society supports the research activity in neuropharmacology, the development of scientific standards, counseling regarding the best methods and techniques to interpret the results but also maintaining the collaboration with the national and international societies, governmental organizations, professional associations, as well as other types of groups, societies, institutions, etc., which contribute in the development of the clinical neuropharmacology field. During During the event, the following works and papers were presented: Prof. Dafin F. Mure\u015fanu, MD, Romania - Advances in neurorehabilitation fundamentals - an update, Results from a large retrospective cohort trial in TBI, Pharmacological support in traumatic brain and spinal cord injury, The role of neurotrophic factors in brain protection and recovery after stroke; Prof. Albert Ludolph, MD, Germany - ALS genotypes and phenotypes; Prof. Heinrich Binder, MD, Vienna, Austria - The forgotten autonomous system in early rehabilitation, What\u2019s the meaning of early rehabilitation in neurodegenerative diseases?; Prof. Ovidiu B\u0103jenaru, MD, Romania - Neurorehabilitation strategy in patients with focal dystonia, Brain cholesterol: implications in the treatment of neurological diseases; Prof. Amos D. Korczyn, MD, Israel \u2013 Disease course modification in Parkinson\u2019s disease, Vascular Parkinsonism, Medically unexplained symptoms in neurology.Moreover, other works were also presented: Prof. Johannes Vester, MD, Germany \u2013 Is there a chance for clinical research in neurorehabilitation within the framework of evidenced-based medicine? Classic and new approaches; Prof. Gelu Onose, MD, Romania \u2013 Propaedeutics for rehabilitation in the central nervous system traumatology (postacute/ subchronic stages); Prof. Adriana Sarah Nica, MD, Romania \u2013 Nutritional care of neurological disabled patients; Prof. Mihaela Baciu\u0163, MD, Romania - The benefit of high-end neurological therapy in maxillofacial surgery; Prof. Tudor Lupescu, MD, Romania \u2013 Symptomatic treatment in diabetic neuropathy; Prof. Vitalie Lisnic, MD, Republica Moldova - Impairment of the central nervous system in demyelinating polyneuropathies: neurophysiological, clinical and neuroimaging aspects, Atypical forms of chronic inflammatory demyelinating polyneuropathy, etc. What has already become a tradition is the care of the organizers for the variety and diversity of the actions auxiliary to the scientific ones, which have also been surprising on this event. And, it could not have been otherwise, since it was for example a moment, which was aptly chosen from the works of some illustrious classical music composers, such as Verdi, Rossini, Leoncavallo, Bizet, Offenbach, Lehar, from a bunch of immortal canzonets or traditional Russian or Jewish music, a moment which entirely belonged to the members of the National Opera in Cluj, who are young but very talented, impressing and completing the exceptional scientific congress. Executive EditorAssoc. Prof. Dr. Eng. Victor Lorin Purcarea"} +{"text": "Intelligent materials are claimed to overcome current drawbacks associated with the attainment of high standards of life, health, security and defense. Membrane-based sensors represent a category of smart systems capable of providing a large number of benefits to different markets of textiles, biomedicine, environment, chemistry, agriculture, architecture, transport and energy. Intelligent membranes can be characterized by superior sensitivity, broader dynamic range and highly sophisticated mechanisms of autorecovery. These prerogatives are regarded as the result of multi-compartment arrays, where complementary functions can be accommodated and well-integrated. Based on the mechanism of \u201csense to act\u201d, stimuli-responsive membranes adapt themselves to surrounding environments, producing desired effects such as smart regulation of transport, wetting, transcription, hydrodynamics, separation, and chemical or energy conversion. Hopefully, the design of new smart devices easier to manufacture and assemble can be realized through the integration of sensing membranes with wireless networks, looking at the ambitious challenge to establish long-distance communications. Thus, the transfer of signals to collecting systems could allow continuous and real-time monitoring of data, events and/or processes. Under the effect of one or more external stimuli\u2014ocedures .Based on the \u201csensing-to-action\u201d sequence, stimuli-responsive membranes can offer attractive solutions to numerous applications in the field of textiles, biomedicine, environment, agro-food, water treatment, agriculture, architecture, transport and energy ,3,4.Conceptually, the membrane is considered as a semi-permeable interface able to block the passage of some species while other substances are transported from one phase to another, under steady or unsteady conditions. The transport can be controlled through different mechanisms depending on the membrane feature-types, stream chemistry, and process engineering ,6,7,8. Unquestionably, in the last years the membrane science has gained a leadership in traditional areas such as separation, purification, chemical and energy conversion, by-products reduction, development of artificial organs, and so on .However, it is quite surprising how the way of perceiving the concept of membrane has been progressively changed, leading to an emerging and always more expanding area of research, wherein membrane and sensor technologies are vigorously examined in an attempt to mimic the behavior of natural systems, which are regarded as \u201cmulti-reservoirs of intricate and miniaturized smart functional architectures\u201d ,12,13,14In this frame, many efforts have been done so far in order to make the membranes adaptable, self-maintaining and self-healing like objects, animals and vegetables broadly distributed in nature. Thus, it is not difficult to imagine how transport, wetting, transcription, hydrodynamics, and chemical or energy conversion can be triggered through artificial membranes having a flat, tubular or spherical configuration ,17,18,19A major success is realized when the control of the matter occurs on nano and microscale ,21,22. I2 and O2, is surely an attractive challenge for application in packaging, where prolonged freshness, quality monitoring, safety and harmless shipping/storage represent important prerogatives.Undoubtedly, the creation of interactive and ultra-smart membranes will bring substantial changes in technology, economy, lifestyle and society. It is enough to imagine the advantages arising from the use of intelligent membranes in architecture, agriculture, textiles, pharmaceutical, food and beverage industries. The ability of membranes to stop the air permeability and change the water transmission rate, depending on the direction of heat flow and relative humidity, is expected to promote the development of smart and energy-saving constructions over seasonal time, but also to make textiles comfortable and adaptable to extreme activities and environmental conditions. The smart regulation of vapors and gases, including COBiotechnology is another area where intelligent membranes are in great demand for human health, defense and security. Stimuli-responsive membranes, working as reservoirs of target molecules for targeted therapies or against harmful agents, represent the focus of many current membrane-based studies as well as membranes working like chemical valves and of interest for selective bio-separations, ion-transport and molecular capture. Membranes capable of detecting, stopping and/or quickly destroying contaminants and dangerous chemical or biological compounds could come into play in military, aerospace, biomedicine, water treatment or environmentally hazardous compartments as well.Also, smart membranes perform a fascinating function when used for self-cleaning and self-healing purposes. Combining morphological features with sensing chemical elements, it is possible to save original properties and integrity of the membranes, taking advantage of preventing fouling phenomena, dirty/soil adhesion or damage in the structure and/or chemistry. Optimistically, the future is the miniaturization of adaptive materials and nanosensors in membranes with a major ambition to connect the latter to wireless networks in order to transfer/store signals and data, establishing long-distance communications. It is evident that the achievement of this target could fully revolutionize the lifestyle of everyone and especially that of sportsmen, astronauts, babies, soldiers and the sick. The integration of conductive wearing membranes in textiles appears to be, for example, a viable route towards the fabrication of comfortable electronic devices, enabling to detect in real-time vital functions such as breathing, cardiac frequency, sweat, temperature, blood, and posture .Future prospects involve highly motivated membrane technologists working on the creation of membranes such as complex arrays where new properties can be accommodated for, giving varied smart responses to direct inputs arising from the surrounding environment and, therefore, provide benefits without sacrificing performance. Then, the dream may come true \u2026."} +{"text": "There is no affiliation indicated for the first author, Wang Nguitragool.\u00a0Wang Nguitragool is affiliated with: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. The publisher apologizes for this error, which was introduced during the typesetting process."} +{"text": "Frontiers in Psychology, 2015, Vol. 6, Art. 192), on page 6, Figure In the article \u201cBayesian reasoning with ifs and ands and ors,\u201d by Nicole Cruz, Jean Baratgin, Mike Oaksford, and David E. Over (The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This study was conducted to assess the relation between allergic rhinitis (AR), acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) and environment, comorbidity and ethnicity.A posted GA2LEN screening questionnaire was sent to all those in a random sample of Dutch population (n=16700) in three different areas.The prevalence of ARS is significantly related to AR, a doctor\u2019s diagnosis of CRS, urticaria, eczema, smoking, gender, ethnicity and age. The prevalence of CRS is significantly related to AR, a doctor\u2019s diagnosis of CRS, urticaria, adverse response to painkiller, smoking, ethnicity, asthma and age. The prevalence of AR is significantly related to a doctor\u2019s diagnosis of CRS, urticaria, eczema, adverse response to painkillers, smoking, occupation, ethnicity, asthma, age, CRS and ARSSome environmental factors, comorbidity and ethnicity are positively or negatively related to AR, ARS and CRS. Place of residence in the Netherlands is not related to the prevalence of these diseases."} +{"text": "Scientific Reports6: Article number: 1876410.1038/srep18764; published online: 01082016; updated: 08192016.In the original version of this Article, there was an error in Affiliation 1 which was incorrectly given as \u2018Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China\u2019. The correct affiliation is listed below:\u2018Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China\u2019.This error has now been corrected in the PDF and HTML versions of the Article."} +{"text": "In this period, I could not start this editorial without wishing all of you a Happy New Year.This is also the opportunity for me to warmly thank, for their confidence, our authors, readers, reviewers, members of the editorial board, sponsors, as well as members of MDPI AG in Basel, Beijing, and Wuhan.Pharmaceuticals at the end of January, I was told that the job would be challenging and exciting. It was true, but I got a great deal of support from the scientific and administrative teams of MDPI AG. That allowed us to accumulate excellent results during the past year. Visibility of Pharmaceuticals increased from 458,383 full-text views in 2014 to 608,080 in 2015, a jump of almost 30%. Three Special Issues have been successfully completed. They were dedicated to mitochondrial target-based drug discovery [When I was offered the position of Editor-in-Chief of In 2015, eight distinguished scientists joined the Editorial Board: Jean Pierre Bazureau , Tien L. Huang , Joachim Jose , Christopher W. K. Lam , Viktor P. Lozitsky , Louis M. Mansky , Suzanne Peyrottes , and Maria Emilia de Sousa . Annie Mayence acts as a new associate editor.Pharmaceuticals has affirmed its status of international scientific journal by sponsoring a series of events among which:23. Jahrestagung der Arbeitsgemeinschaft Radiochemie/Radiopharmazie, Erlangen, Germany;\u00e8mes Journ\u00e9es Franco-Belges de Pharmacochimie, Spa, Belgium;291st joint European Conference on Therapeutic Targets and Medicinal Chemistry, M\u00fcnster, Germany;23rd National Meeting on Medicinal Chemistry, Salerno, Italy;11\u00b0 Encontro Nacional de Quimica Organica/4\u00b0 Encontro de Quimica Terapeutica, Porto, Portugal;Ricai 2015: 35th Interdisciplinary Meeting of Anti-infective Chemotherapy, Paris, France.Pharmaceuticals was the proud organizer of the First International Electronic Conference of Medicinal Chemistry [The journal was also present at the 250th American Chemical Society National Meeting and Exhibition in Boston, MA, USA. In addition, last but not least, hemistry . Membershemistry .Pharmaceuticals. We are also proud to let you know that the journal will organize a competition awarding one travel grant [No time for napping; in 2016 we must confirm the promising results obtained during 2015. Increasing the visibility of our journal will remain one of our main goals. We are already working in that direction, and we are pleased to announce that the Second International Electronic Conference on Medicinal Chemistry will takel grant . It will"} +{"text": "An old saying states that \u2018\u2019children are not little adults\u201d and this certainly holds true for celiac disease, as there are many peculiar aspects regarding its epidemiology, diagnosis, clinical presentations, associated diseases, and response to treatment in pediatric compared to adult populations, to such an extent that it merits a description of its own. In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation. In general, the clinical guidelines for diagnosis recommend starting with specific serologic testing in all suspected subjects, including those suffering from extraintestinal related conditions, and performing upper endoscopy with appropriate biopsy sampling of duodenal mucosa in case of positivity. The latter may be omitted in young patients showing high titers of anti-transglutaminase antibodies. The subsequent management of a celiac patient differs substantially depending on the age at diagnosis and should be based on the important consideration that this is a lifelong condition. In fact, in a substantial number of cases, both in adults and children, the disease remains clinically silent and the only manifestation is the associated disease/s [i.e., endocrinologists, rheumatologists, orthopedists etc., who need to be aware of this association [The number of conditions possibly associated with CD is extensive enough to justify active screening for most of them, with an estimated prevalence of 30.1% in adulthood and 20.7% in childhood . The mosisease/s ,63 for wociation . Here bevice versa.Surely, diabetes mellitus type I is the most frequent autoimmune disease associated with CD , with a An increased prevalence of autoimmune thyroid diseases, namely Hashimoto\u2019s and Graves\u2019 diseases, has been described in adults and to a greater extent in children with CD, although the rate varies amongst studies ,80,81,82i.e., Sj\u00f6gren\u2019s syndrome [Other than type 1 diabetes and thyroid autoimmune diseases, further endocrine conditions, such as Addison\u2019s disease and primsyndrome , systemisyndrome , and juvsyndrome , skin disyndrome , hepaticsyndrome , neurolosyndrome , cardiolsyndrome and idiosyndrome , althougsyndrome . Similarsyndrome , has beesyndrome . Here beSjogren\u2019s syndrome is an autoimmune exocrinopathy characterized by dry eyes, dry mouth, and circulating antibodies against intracellular proteins. The association between Sjogren\u2019s syndrome and CD was first described in 1965 . Since tSelective IgA deficiency is one of the most frequent immunologic disorders associated with CD, with a reported frequency of 1:39 in populations of both adult and childhood CD , compareOther than gluten ataxia, a wide range of neurological and psychiatric disorders, such as peripheral neuropathy, epilepsy, headaches, dementia, depression, autism, and schizophrenia has been reported in association with CD, both in childhood and adulthood, although the risk seems higher in adulthood . In partThe relationship between dermatomyositis and CD has been suggested, both in young adult and adults ,119, witPossible conditions associated with CD, mainly in childhood, include elevated serum aminotransferases, without any specific histological changes that promptly reverse after a course of GFD, now known as \u201cceliac hepatitis\u201d , as wellObviously, this problem affects only CD in adulthood, where the association of infertility in both women and men is recogFollowing the established association with some genetic disorders, namely Down\u2019s, Turner, and Williams syndrome, CD screening is highly recommended for these conditions. The prevalence of CD in Down\u2019s syndrome patients, indeed, ranges from 4% to 18%, according to several studies performed in both the USA and Europe ,134,135,Pending a better understanding of its pathogenesis ,2, the tThe term complicated CD encompasses a spectrum of different conditions, namely refractory CD (RCD), ulcerative jejunoileitis (UJI), and enteropathy-type-associated T cell lymphoma (EATL), which represent a biological continuum and are estimated to affect only a few cases in the adult CD population ,3,163. TIn conclusion, despite previous evidence that adult CD carries a twofold increase in all-cause mortality, and 60-fold increase in non-Hodgkin lymphoma compared with the general population , a recenTaken together, these findings highlight how different CD in children appears compared to CD in adults. First, the disease seems more common in children than in adults ,178 prob"} +{"text": "July 2015 marks the 25th anniversary of the passage of the Americans with Disabilities Act (ADA), signed into law on July 26, 1990, by President George H.W. Bush. ADA prohibits discrimination against persons with disabilities in all areas of their everyday lives, such as work, school, transportation, communication, recreation, and access to state and local government services. When first enacted, ADA defined a disability as a \u201cphysical or mental impairment that substantially limits one or more of the major life activities.\u201d.http://www.cdc.gov/ncbddd/disabilityandhealth/.For more information on disability research and surveillance and state and national disability programs and resources, access the CDC\u2019s Disability and Health Branch, available at"} +{"text": "Objectives: Considering the increasing prevalence of depression in modern societies and the positive effects of omega-3 polyunsaturated fatty acids on depression, this study aims to investigate the omega-3 and omega-6 content of various foodstuffs, prescribed or prohibited by Iranian Traditional Medicine (ITM).Materials and Methods: Firstly, reliable sources of Iranian Traditional Medicine were reviewed in order to identify the prescribed and prohibited foodstuffs for depressed patients. Afterwards, according to the online database of United States Department of Agriculture , the ratio of linoleic acid to alpha linolenic acid was identified in each foodstuff. Finally, the ratios of omega-6 to omega-3 were compared between seven food groups of vegetables, fruits, dry goods, high protein products, dairies, breads, and spices.Results: Based on the resources of Iranian Traditional Medicine, the following foods are prescribed for depressed patients: basil, coriander, spinach, lettuce, squash, peppermint, dill, chicory, celery, beet, quince, cucumber, watermelon, grape, peach, pomegranate, banana, apple, currant, pistachio, dried fig, almond, egg, chicken, lamb, trout, milk, bread without bran, saffron, oregano, and coriander seeds. On the other hand, cabbage, eggplant, onion, garlic, broad beans, lentils, beef, whole wheat bread, and mustard are prohibited. It should be noted that omega-3 content in some prescribed foods is more than that of the prohibited ones.Conclusion: The present study showed that mint, basil, spinach, lettuce, squash, lamb, saffron, oregano, cucumber, pistachio, milk, and also wild trout can be considered as medicinal foods for depressed patients. Recently, a great deal of attention has been paid to the use of therapeutic methods for depression, based on Complementary and Alternative Medicine (CAM) as a CAM involves several non-pharmacological treatments, among which food therapy is the most notable. Although the effectiveness of different diets, such as the Mediterranean diet, in preventing depression . It should be noted that the values of linoleic acid and alpha linolenic acid are considered relative to the amount of omega-6 and omega-3, respectively. In the next step, the ratio of omega-6 to omega-3 was determined for each of the foodstuffs in seven food groups, including vegetables, fruits, dry goods, high protein products, dairies, breads, and spices. Finally, in each of the aforementioned groups, the obtained ratios were compared with each other. At first, reliable ITM texts including Kamel al-Sanaat al-Tibbyyah, Al-Qanun fi al-Tibb and Zakhireh Kharazmshahi were reviewed for prescribed and prohibited foods in depression. Given to the positive impacts of polyunsaturated fatty acids on depressed patients and for investigating omega-3 content of the foodstuffs, in the next step the amounts of omega-3 and also omega-6 polyunsaturated fatty acids for each of the foodstuffs were collected from the USDA database , in the vegetables group, the ratio of omega-6 to omega-3 in mint, spinach, basil, lettuce, and squash is less in comparison with all the prohibited vegetables. However, this does not apply to coriander, dill, chicory, celery, and beet, which are prescribed in this group was higher than those of lamb (3:1) and beef (2:1). Therefore, based on our findings, beef and lamb are preferable to trout, with regard to their omega-3 content. Since the approximate ratio of omega-6 to omega-3 in wild trout is 2:1, this contradiction could be related to selecting framed trout instead of wild trout in this study.Recent studies show the negative effect of non-bran grain consumption on depression (Jacka, 2010On the other hand, modern medicine databases have reported the antidepressant effect of garlic (Dhingra and Kumar, 2008In the present study, we studied only the USDA database for polyunsaturated fatty acids values, while reports by other resources were neglected. Because this database is one of the most valuable and well-known resources in this domain, the obtained results are most likely reliable.Other limitation of this study is that the effects of other nutrients have not been considered. Omega-3 is only one of the effective nutrients for depression management and there are many other nutrients that have positive effect on depression. Therefore, it is not possible to confirm the antidepressant effects of foodstuffs only by relying on their fatty acids content. As the final point, mint, basil, spinach, lettuce, squash, lamb, saffron, oregano, cucumber, pistachio, milk, and also wild trout can be considered as medicinal foods for depressed patients. On the other hand, cabbage, eggplant, onion, broad beans, lentils, beef, and mustard do not have such effect. By definition, medicinal foods not only provide the required nutrients, but also promote the health status of an individual (Esfahani et al., 2011As previously mentioned, polyunsaturated fatty acids are only part of the nutrients affecting depression and nutrients are only part of the effective ingredients in a foodstuff. Accordingly, research on the effects and amounts of other nutrients in the studied foodstuffs would be helpful in achieving more accurate results. Moreover, it would be advantageous to design observational or interventional studies based on the main findings of this study."} +{"text": "PLoS Biology, volume 2, issue 3:In Table of ContentsPage iiiThis photograph was used on the March 2004 Table of Contents, where Adam Lazarus, who generously supplied the image, should have been acknowledged. We apologize for this omission."} +{"text": "Scientific Reports 10.1038/s41598-022-22323-9, published online 17 October 2022Correction to: The original version of this Article contained an error in the Funding section.\u201cThis work is funded by Pusan National University Research Grant 2020. The funder had no role in study design, data collection, software development, data analysis, data interpretation, writing of the report, or decision to submit the paper.\u201dnow reads:\u201cThis work was supported by a 2-Year Research Grant of Pusan National University. The funder had no role in study design, data collection, software development, data analysis, data interpretation, writing of the report, or decision to submit the paper.\u201dThe original Article has been corrected."} +{"text": "The development of nanomaterials with different shapes and sizes and which are utilized as effective materials for energy and environmental applications constitutes a challenge for researchers ,2,3,4,5.This Special Issue also collected various research articles addressing catalysis, which is used in different applications; for example, Boyu Li, et al. reported"} +{"text": "Movement is fundamental to life, shaping population dynamics, biodiversity patterns, and ecosystem structure. In 2008, the movement ecology framework :19052\u201319059, 2008) introduced an integrative theory of organismal movement\u2014linking internal state, motion capacity, and navigation capacity to external factors\u2014which has been recognized as a milestone in the field. Since then, the study of movement experienced a technological boom, which provided massive quantities of tracking data of both animal and human movement globally and at ever finer spatio-temporal resolutions. In this work, we provide a quantitative assessment of the state of research within the MEF, focusing on animal movement, including humans and invertebrates, and excluding movement of plants and microorganisms. Using a text mining approach, we digitally scanned the contents of De motu animalium 384-322 BC) and mechanistic perspectives by Marshall et al. ) Methods section\u2014or any other section except for tables.The dictionary analyses showed high precision at identifying the papers associated with each MEF component, taxonomic group, tracking device, software, and type of statistical method . Only analyzedThe topic analysis showed general consistency . The word intrusion approach is not an exhaustive assessment of topic interpretability, but it allows putting our results into perspective: some topics have a clear and easy interpretation and some others are really hard to interpret. In ecology, topic models have been recently used to identify themes in ecology and asseEach stage of the text mining approach assumed that there were no changes in the terms used in the literature to refer to the same concepts over the decade 2009\u20132018. While this assumption is likely to be false, it would be reasonable to expect that there have not been drastic changes in terminology within a single decade. We recommend that future studies also embrace text mining techniques, since the number of publications and the rate of publications are only expected to increase. For studies encompassing a longer time frame, it could be more useful to use the methods and criteria described here as a starting point\u2014rather than the exact keywords or model parameters\u2014and either train the algorithms over a decade and validate over others, or train a different algorithm for each time period. In any case, the validation process, which requires manual verification of a sample of papers, is key to support the findings; here, they returned high precision for identifying movement papers and high accuracy for each dictionary. \ufeffIn retrospect, we also encourage using version control when calibrating algorithms and keywords to keep track of the development process and get better performance in a more efficient way.In the article introducing the MEF , technolOur results showed a steady growth in the use of R. The same pattern in reported R usage was observed in the field of ecology globally . AccordiIn parallel, there has been substantial progress in the number and sophistication of quantitative methods for the study of movement , 60 and https://rociojoo.github.io/mov-eco-review/survey-about-movement-ecology.html). Respondents (32 out of 33) indicated that technology and methods to collect and analyze data were the features that revolutionized the field in the last decade\u2014this has been coined the \u2018biologging revolution\u2019 [www.IcarusInitiative.org, accelerometers, multisensor loggers) will also be driving the field in the following decade.The results obtained here were consistent with the perspectives of movement ecologists who answered a limited survey in the winter and spring of 2019 , we would have expected to find an increase in the study of the internal state, motion, and navigation, as well as in the percentage of studies addressing other components of the MEF in combination with external factors. Research on internal state showed a small growth over the years, which could be due to an increase in the number of studies investigating the links between energetic conditions and behavior within tracks , or the Addressing all of the components of the MEF requires interdisciplinary efforts involving researchers from ecology, biology, neuroscience, physics, statistics, and geographic information science, among others , 35. TheOverall, the topic analysis revealed both the fragmentation of the movement ecology community based on taxonomic groups, and the potential for synergies across taxonomic groups. In particular, we were able to quantitatively categorize topics clearly associated to specific taxa, notably in the aquatic realm . Humans (two topics about sports and activity patterns) and birds (one topic about migration) were also strongly associated to given topics, further reinforcing a pattern of study of large, easy to tag fauna that work as model species. On the other hand, the majority of topics did not show fidelity to any taxon, which suggests their potential for generalization\u2014and integration\u2014across taxa, for instance using shared methods or devices. Among these, two groups of topics can be identified, dealing with subject areas and technological and methodological concerns , both of which lay the foundations for further interdisciplinary research and knowledge transfer.Integrated research also requires overcoming communication difficulties , 65, devThe progress made in terms of tools for data collection, processing, and analysis needs to be shared with the community to foster a better and more integral understanding of movement in all of its aspects. In this respect, the FAIR principles , 72 offeBy congregating the community around the R environment, most movement researchers can communicate over the same programming language, share codes, and move towards transparency, collaboration, and reproducibility. In an era with large volumes of data and much dependency on software for the analyses, reproducibility in science also requires open code . On\ufeff theImprovements in technological devices to track animals and humans have generated high volumes of movement data from a range of species, providing greater information on their movement paths, physiology, and the environment they experience. However, there has been little change in the degree to which studies address different components of the MEF, while there are also distinct groups of research topics that are predominantly linked to the species studied , the methods used and their application. Developments in statistical methods and software tools have facilitated data processing and analysis. These aspects have been clear drivers of movement research in the 2009\u20132018 decade and will likely continue to drive the field, allowing to explore new research questions and improve our understanding of evolutionary, physiological, and life-history causes and consequences of movement. To make that possible, there should be strong commitments towards transparency, reproducibility, and interdisciplinary collaboration practices in the community.https://rociojoo.github.io/mov-eco-review/, serving as the manuscript\u2019s Supplementary Information page. It contains an Introduction (to the website) and the abstract (section 1), a description of Data collection and processing (section 2), Data analysis with a description of methods and layout of results (section 3), the description and results of the Survey about movement ecology (section 4), and details on the R session used for these analyses. The R codes are available in a GitHub repository https://github.com/rociojoo/mov-eco-review, and links to specific R codes are provided in the text of the website.Additional file 1\u2014Companion website: This is the companion website for the manuscript, Fig. 1: Time line of movement articles, with the number of articles published in the y-axis, and the years in the x-axis. There is an increasing trend in the number of articles going to almost 1200 papers in 2018. In this time line, we also highlighted events in the history of movement studies: The philosophical study of movement , the mechanistic study of movement , Quantitative analysis of movement , the introduction of movement as a framework , a Biotelemetry and biologging issue in JAE, and a movement ecology special feature in PNAS (both in 2008), the GPS in animal ecology theme issue in PTRSB (2010), the start of the Movement Ecology journal (2013), the movement ecology virtual issue in JAE (2015), and the collective movement ecology issue in PTRSB (2018).Fig. 2: Graphical representation of the algorithm to identify movement papers. First, define KEYWORDS for Web of Science and search. Get results on N papers. Then do quality control, consisting of selecting a random sample n (n = 100) from N, reading the abstracts, determining if they are from movement studies and computing a precision metric. If precision is greater than 0.8 and N is greater than 5000, we stop. Else, we edit keywords and do it all over again.Fig. 3: Proportion of papers in each year studying each of the five most commonly studied taxonomic groups. The years are in the x-axis, the proportion of papers in each year in the y-axis, and dots of different colors (one per class) correspond to the value of proportion for each year. In all years from 2009 to 2018, mammals (orange) were the most studied group, followed by fish (sky blue) , birds (green), humans (blue), and insects (dark orange). Only from 2012 there were more studies concerning humans than those of insects.Fig. 4: Number of species studied in each year for the five classes with most studied species . More species have been studied in the last years in general.Fig. 5: Proportion of papers in each year using the five most commonly used tracking devices. The years are in the x-axis, the proportion of papers in each year in the y-axis, and dots of different colors (one per device) correspond to the value of proportion for each year. GPS (orange) showed an increasing trend and was the most used device in movement papers in all years. Radio telemetry (sky blue), showed a decreasing trend, and started in 2009 with the same proportion of studies as GPS, and ended in 2018 in third place, below accelerometer (green). In contrast, accelerometer was in fifth position in 2009 and increased its popularity over the years. Acoustic telemetry (yellow) and satellite technology (blue) were tied in fourth place in 2018.Fig. 6: Proportion of papers in each year using the five most commonly used software. The years are in the x-axis, the proportion of papers in each year in the y-axis, and dots of different colors (one per software) correspond to the value of proportion for each year. R (orange) showed an increasing trend, starting at the last position of the five in 2009, and ending in first place in 2018 (with 0.7 of studies using it). The other four software showed decreasing trends over the years. ArcGIS (sky blue), SPSS (yellow), Matlab (green), and SAS (blue), ended up in second, third, fourth, and fifth positions, respectively, in 2018.Fig. 7: Proportion of papers in each year mentioning each type of statistical method. The years are in the x-axis, the proportion of papers in each year in the y-axis, and dots of different colors (one per type of method) correspond to the value of proportion for each year. Generic methods (orange) were the most popular throughout 2009-2018, while movement (sky blue), spatial (green), time series (yellow), social (blue), and spatiotemporal (dark orange), remained in second, third, fourth, fifth, and sixth position, respectively, throughout the decade.Fig. 8: Proportion of papers in each year focusing on each component of the MEF. The years are in the x-axis, the proportion of papers in each year in the y-axis, and dots of different colors (one per component) correspond to the value of proportion for each year. In all years from 2009 to 2018, external factors (orange) were the most studied component, followed by internal state (sky blue), motion (green), and navigation (blue).Fig. 9: Bar plots of the proportion of papers studying each taxonomical group for each component of the MEF. The number of papers where taxonomical groups were identified by our algorithm for each component are indicated in the figure: 3475 for external factors, 2141 for internal state, 1106 for motion, and 368 for navigation. In all components, mammals were the most studied. For external factors, fish and birds were the second and third most studied groups, respectively. For internal state, they were birds and fish, in that order. For motion, fish and humans. And for navigation, fish and insects, followed closely by birds.Fig. 10: Topic analysis. A: Word clouds of each topic based on beta values. The area occupied by each word in each wordcloud is proportional to beta. In topic 1, the largest words are individual, behavior, movement, dispersal, population. In topic 2, model, data, movement, time, estimate, method. In topic 3, habitat, movement, landscape, selection. In topic 4, animal, data, behavior, study. In topic 5, range, home, movement, site, size, population, individual, kilometer. In topic 6, movement, fish, habitat, tag, shark. In topic 7, forage, prey, behavior, dive, seal. In topic 8, speed, behavior, animal, movement, swim, body. In topic 9, fish, behavior, tag, river, acoustic. In topic 10, behavior, human, signal, sensor, activity, motion. In topic 11, activity, behavior, time, temperature, day. In topic 12, bird, migration, flight, migratory, wind. In topic 13, player, distance, play, speed, train. In topic 14, female, male, sex, activity, behavior, sex, age. In topic 15, turtle, whale, nest, behavior, breed, adult. B: Bar plots of proportion of papers studying each taxonomical group for each topic. Regarding dispersal (n = 345 papers), the most studied groups were mammals, human and amphibians. For movement models (n = 200), they were mainly mammals and humans. In habitat selection (n = 535), most studies pertained mammals. In detection and data (n = 134), also a majority of mammals. In home ranges (n = 233), it was mostly birds, followed by mammals. In aquatic systems (n = 384), an overwhelming majority of fish. In foraging in marine megafauna (n = 323), it was mostly birds, followed by mammals. In biomechanics (n = 268), insects, fish and mammals were the most studied groups. In acoustic telemetry (n = 290), fish were the most studied, followed by mammals. In experimental designs (n = 227), humans and mammals were the most studied groups. In activity budgets (n = 191), mammals were the most studied, followed by fish. In migration (n = 146), birds were the most studied group. In sports (n = 122), almost all studied involved humans. In human activity patterns (n = 106), it was humans, followed by mammals. In breeding ecology (n = 159), it was mostly reptiles, followed by mammals, birds, and fish."} +{"text": "In \u201cPredictors of Health Information\u2013Seeking Behavior: Systematic Literature Review and Network Analysis\u201d :e21680) the authors noted three errors.1. In the originally published article, Reference 11 was incorrectly published as follows:Cole C. Looking for information: a survey of research on information seeking, needs, and behavior (4th edition). Donald O. Case and Lisa M. Given. Bingley, UK: Emerald Group Publishing, 2016. 528 pp. $82.95 (hardcover). (ISBN: 9781785609688). J Asso Inf Sci Technol 2016 Dec 21;68(9):2284-2286. [doi: 10.1002/asi.23778]The correct reference is a book and has been updated as follows:Case DO, Given LM. Looking for information: a survey of research on information seeking, needs, and behavior (4th edition). Bingley, UK: Emerald Group Publishing; 2016.2. The in-text citation for reference 11 incorrectly mentioned the year as 2002 in the following sentence:Other known models from the information science perspective include the Comprehensive Model of Information Seeking, which looks at information carrier characteristics, antecedents, and information-seeking actions [10] and the book by Case in 2002 about the research on information-seeking needs and behaviors [11].The correct year for the current edition of the book is 2016 and the sentence has been updated as follows:Other known models from the information science perspective include the Comprehensive Model of Information Seeking, which looks at information carrier characteristics, antecedents, and information-seeking actions [10] and the book by Case in 2016 about the research on information-seeking needs and behaviors [11].3. In affiliations 1 and 2 of the originally published article, the city was incorrectly mentioned as 'The University of Sydney'. This has been corrected to 'Sydney,' and the correct list of affiliations is as follows:1*, BPharm, MPhil, GCertEdStud (Higher Ed); Parisa Aslani1*, BPharm, MSc, PhD, GCertEdStud (Higher Ed); Edward Joseph Luca2, BA, MBA; Carl Richard Schneider1*, BN, BPharm, PhD, PGCert (Higher Ed)Ardalan Mirzaei1School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, Australia2The University of Sydney Library, The University of Sydney, Sydney, Australia*these authors contributed equallyThe correction will appear in the online version of the paper on the JMIR Publications website on June 3, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Thanks for your observations and for giving us a chance to reply to the letter you received about our paper entitled: \u201cThe relationship between body mass index and preeclampsia: A systematic review and meta-analysis\u201d. In the following, the authors have tried to answer the issues raised as much as possible:The quality assessment was done by the Newcastle-Ottawa Scale, 27 articles with a quality score of Many statistical tests, such as Begg and Mazumdar (1994), can be used to check publication bias. In this article, we report the p-value and a plot in the results section, which seems to be sufficient , Figure 5). Egger et al. proposed a test for the asymmetry of the funnel plot. The power of this method to detect bias will be low with small numbers of studies. Begg and Mazumdar proposed testing the interdependence of variance and effect size using Kendall's method. This bias indicator makes fewer assumptions than that of Egger et al. .Pubmed and Scopus databases for English and SID for Persian articles had good coverage for our search, no search results for additional articles were found on Web of Sciences. Using the Web of Sciences is not obligatory in search of all meta-analysis studies. In our investigation, there were neither any articles in the Web of Sciences nor in PubMed and Scopus databases.Subgroup analysis were done according to mild and severe preeclampsia . To pool the results of articles, there were alternative, fixed effect models, (when heterogeneity is not significant) and random effect models (when heterogeneity is significant) (5).Effect size was defined by the researcher as mean BMI with a 95% confidence interval (CI), when we use CI there is the sample size in its formula (mean Effect size can be defined as mean difference, or SMD, WMD, OR, RR, if we use SMD it would lead to an increase in missing values, SMD is computed when mean, SD, and sample size are available in both cases and control groups, but when we define mean BMI as effect size, it is not necessary we have mean, SD, and sample size in both groups.Consequently, the results of this article, according to pooled results of 16 high-quality articles, are valid to cite.1 M.D., Mohammad Rafiei2 Ph.D., Mostafa Rezaei Tavirani3 Ph.D., Kourosh Sayehmiri4 Ph.D., Majid Dousti4 Ph.D.Morteza Motedayen1Department of Cardiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.2Department of Biostatistics and Epidemiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.3Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.4Psychosocial Injuries Research Center, Department of Biostatistics, School of Public Health, Ilam University of Medical Sciences, Ilam, Iran."} +{"text": "Algae have been consumed for millennia in several parts of the world as food, food supplements, and additives, due to their unique organoleptic properties and nutritional and health benefits. Algae are sustainable sources of proteins, minerals, and fiber, with well-balanced essential amino acids, pigments, and fatty acids, among other relevant metabolites for human nutrition. This review covers the historical consumption of algae in Europe, developments in the current European market, challenges when introducing new species to the market, bottlenecks in production technology, consumer acceptance, and legislation. The current algae species that are consumed and commercialized in Europe were investigated, according to their status under the European Union (EU) Novel Food legislation, along with the market perspectives in terms of the current research and development initiatives, while evaluating the interest and potential in the European market. The regular consumption of more than 150 algae species was identified, of which only 20% are approved under the EU Novel Food legislation, which demonstrates that the current legislation is not broad enough and requires an urgent update. Finally, the potential of the European algae market growth was indicated by the analysis of the trends in research, technological advances, and market initiatives to promote algae commercialization and consumption. However, concerns regarding the environmental impact of the current food production systems, together with health and animal welfare issues, have driven the need to develop healthier and more sustainable food sources .Algae\u2014microalgae (including cyanobacteria) and seaweed \u2014have been used as food since medieval times, with a consolidated market in Asia and a growing market in Europe, being driven by a rising awareness in consumers regarding sustainable and healthy foods ,3,4,5. ISpirulina, 36% seaweed, and 10% microalgae. The remaining 8% produce both Spirulina and microalgae [In 2009, the European Algae Biomass Association (EABA) was founded to promote the algae industry by establishing synergies between academia, industry, and decision-makers in the field . After tcroalgae ,12,13.Algae can be consumed as food or as ingredients in prepared foods, in a fresh, fermented, dried, or frozen format, either whole or milled into differently sized flakes, granules, or powders ,15. Alga\u03c9-3 PUFA, such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are also earning market relevance, replacing the traditional intake of these compounds via fish consumption [\u03b2-carotene, lycopene, and astaxanthin are mainly used as dietary supplements, food fortifiers, and beverage natural colorants, as the new generation of consumers chooses natural over synthetic products [Moreover, algae are a sustainable source of natural high-value bioactive compounds, with the potential to manufacture new products for human nutrition. Lipids, in the form of polyunsaturated fatty acids (PUFA), \u03c9-3 and \u03c9-6 PUFA, and phytosterols are major compounds in algae that can be applied in several contexts, due to their beneficial properties for the cardiovascular system, anti-cholesterol activity, and others ,36,37,38sumption . Proteinsumption ,45,46,47sumption ,52,53,54sumption ,58,59,60oncerns) ,63,64,65Each category of algae-based products is regulated by separate legislation. For food and food supplements, novel food regulation (EU 2017/2470) is covered in the Novel Food Catalog, a list of authorized novel foods that are safe for human consumption .This review paper addresses the applications of algae as a food in Europe, with an overview of the consumption habits, market, and legislation. Approved and consumed algae species are listed and the challenges of incorporating them into the European market are evaluated, together with the analysis of research and development initiatives.Algae have been included historically in the human diet worldwide. According to archaeological findings in Monte Verde (Chile), people were collecting seaweeds for food and medicine 14,000 years ago . SeaweedPalmaria palmata was traditionally eaten raw, toasted with hot irons, cooked in a thick oatmeal broth, served boiled, tossed in butter, or fried as crisped seaweed \u201cbacon\u201d for sandwiches; later, it was used for chewing tobacco, as well as ingested for deworming and to cure \u201cwomen\u2019s longing\u201d [Porphyra sp. (Atlantic Nori or Purple Laver), baked into different dishes, such as the popular Welsh laverbread (\u201cbara lawr\u201d) from Wales, or fried as an ingredient in omelets or pies , in the Azores Islands [Ulva lactuca (sea lettuce) and Chondracanthus teedei were traditionally eaten fresh by fishermen and beachgoers, with a squeeze of lemon and salt, in coastal regions such as Catania (Sicily) [In Europe, seaweeds are likely to have been harvested for human consumption for centuries, although they are a vastly underexploited resource when compared with consumption in Asia ,72. Archlonging\u201d ,90,91,92longing\u201d ,86,87,91ortugal) ,85,93,94(Sicily) ,96,97. T(Sicily) .Ascophyllum nodosum, known as Rockweed, in Norway; Laminaria digitata, or Oarweed, in France and Ireland; Laminaria hyperborea, or Tangle, in Britain, Ireland, and Norway); harvested Irish Moss in coastal areas and black carrageenan or \u201cDanish Agar\u201d for carrageenan and furcellaran extraction [Porphyra sp.), Wakame (Undaria pinnatifida), Kombu (Laminaria sp.), Agar, Arame (Eisenia bicyclis) and Hijiki (Hizikia fusiforme), which are still largely imported from Asia to this day [Chondrus sp. and Mastocarpus sp.), in mainland Portugal, Spain, and France , the Azorean Islands (Pterocladiella capillacea) and Italy (Gracilariopsis longissima (or Gracilaria verrucosa) [Gelidium corneum and Pterocladiella capillacea peaked in 1980, with Portugal leading as the world\u2019s fifth-largest agar producer and European macroalgae contributing to 34% of the world\u2019s alginate supply [In Western countries, seaweeds have been mainly associated with industrial applications focused on the extraction of phycocolloids for the food industry ,98. In ttraction ,86,88,99this day ,101,102.this day ,101. By this day ,60. The rrucosa) ,109,110.rrucosa) ,112. Fure supply ,110,113.Nostoc species are traditional foods in China , Mongolia, and South America [Arthrospira was historically harvested by the Aztecs living near Lake Texcoco, as recorded in the 14th century as an ingredient for a dry cake called \u201cTecuitlatl\u201d [For microalgae, the oldest documented use as food was 1500 years ago in China ,114. Nosushuru\u201d) ,116,117.uitlatl\u201d . In Afriuitlatl\u201d ,119,120.uitlatl\u201d . The comuitlatl\u201d . Recentluitlatl\u201d ,123,124.Microalgae have only recently been consumed in Europe. From the historical perspective, it is important to highlight that although microalgae were under active research for many decades, especially for the human diet, the product of this research has failed to materialize commercially in the EU space, at least until the publication of Regulation (EC) No. 258/97 of the European Parliament and of the Council of 27 January 1997, concerning novel foods and novel food ingredients ,22,125. The historical role of microalgae ,149,150 The European algae industry, with the production of around 500 t algae dry weight per year, remains a niche market, mainly directed to food and food-related applications and concentrated on the production of large quantities of biomass using a limited number of species ,12. Many\u22121 year\u22121, which may be compared to the consumption of salad in Europe (3 kg per capita\u22121 year\u22121) [Despite the promising figures, the high cost of production, the complexity of European regulations concerning cultivation licenses, and the synchronization of guidelines for organic certification between countries limit the algae market in Europe ,161,162. year\u22121) ,164. Int year\u22121) . European algae producers face heavy competition from Asian producers, mainly due to higher production costs and product prices, which may be discouraging for the producers. However, Asian producers are frequently criticized for the environmental impact caused by their aquaculture systems in eutrophic waters. As this is viewed negatively by an ever more eco-conscious market, European production might excel in the global market of retailers and consumers who demand higher-quality, sustainable algae-based products .The estimated value of the European algae products market is expected to grow by around 43% between 2016 and 2023 , forecasIn Europe, microalgae are commonly produced in photobioreactors in closed and controlled conditions. Germany, France, and Spain host the largest number of producers; however, it is in Portugal that we can find the oldest and the largest microalgae production companies in the EU, Necton and Allmicroalgae, respectively.Chlorella sp. being the most popular. Nevertheless, a wide range of algae has the potential to also be considered for this purpose [\u03b2-carotene, astaxanthin, fucoxanthin, or lutein can be obtained from microalgae, such as Dunaliella salina, Haematococcus pluvialis, Chlorella vulgaris, Microchloropsis gaditana , Auxenochlorella protothecoides, Phaeodactylum tricornutum, Tisochrysis lutea and Spirulina sp. [P. tricornutum, Chlorella sorokiniana or Nannochloropsis oceanica [H. pluvialis, and retinol or \u03b2-carotene obtained from D. salina [One of the key microalgae applications is in the nutraceutical market, in terms of dietary supplementation, where they are seen as valuable natural sources of macro- and micronutrients of great commercial potential ,173. In lina sp. ,178. Furoceanica . In seve. salina ,184,185.Chlorella and Spirulina [Nannochloropsis gaditana and Nannochloropsis oculata, while others, such as Chlorella sorokiniana and Auxenochlorella protothecoides, were being sold without any authorization until recently, when they were approved [Euglena gracilis, Spirulina, and Chlorella, among others, mostly for use in traditional food products such as pasta, ready-to-eat bars, dairy and fermented products, candies, and p\u00e2t\u00e9s [Microalgae can be found either as an ingredient in food products or as a whole-cell powder that can be used freely in cooking recipes, smoothies, drinks, or simple snacks ,188,189.pirulina . In a 20pirulina . It is aapproved ,192,193.nd p\u00e2t\u00e9s ,188,189.The European seaweed industry is still in its early development and has been almost exclusively based on wild stock harvesting, unlike the extensive farming that takes place in Asia . HoweverAscophyllum nodosum, Alaria esculenta, Laminaria hyperborea, L. digitata, Saccharina latissima and Undaria pinnatifida [The value of European seaweed is roughly estimated as EUR 500\u2013600 million per annum , but it is highly dependent on species, whether wild-harvested or farmed, and the targeted market. Leading markets for seaweed are as plant biostimulants for agriculture and the phycocolloid industry, which is focused on the extraction of single products, such as alginic acid, laminaran, and colorants. Europe is the top food and pharma-grade alginate producer worldwide, with a minor share of global carrageenan and agar production ,99,163. natifida ,197.A. esculenta, S. latissima, Porphyra sp., P. palmata, and Ulva sp. [The European seaweed market is developing at a fast pace, with an annual growth rate of 7\u201310% and a wholesale value of around EUR 24 million, focusing only on Ulva sp. ,199,200;Ulva sp. . The proUlva sp. ,22,202. Ulva sp. . Pyropia sp. . Europe has a nominal supply of Atlantic Nori, producing only 1% of what is consumed. On the other hand, 90% of the P. palmata consumed in Europe is regionally wild-harvested in France. In this case, Europe is becoming more proactively competitive, relying on imports to satisfy 10% of the European consumer demand [In 2016, the EU imports of seaweed products were almost twice the size of its exports , making the EU the world\u2019s second-largest importer in terms of volume, valued at EUR 506 million . Marketsr demand .Another use of seaweed in food production is its application in packaging biomaterials, such as for edible pouches or pods to replace drinking bottles .Despite the historical consumption of algae as a food and their associated nutritional and health benefits, there are still bottlenecks blocking its progress from the current niche markets to larger ones. The main reasons are production constraints, high costs, environmental concerns, health and safety, legality, and consumers\u2019 perception of the product .The growth of algae can be affected not only by abiotic factors but also by biological factors and operational factors ,209,210.In order to move to a larger-scale operation, an increase in qualified human resources, mechanization, and automation in the operations is required. The scaling-up of photobioreactors from the laboratory to an industrial scale, for example, is pricey not only due to the high material costs but also because of high operational costs, especially if the algae are being cultivated in a different climate from their original habitat. The temperature and light control in this case significantly increases the energy costs of the operation .The appearance of biological contaminants during algae cultivation is also a constraint that can compromise cultures and lead to enormous economic losses. Like most other farming activities, algae cultivation suffers from contamination by parasites, epiphytes, epizootics, competitors, grazers, and predators ,217,218.In the case of microalgae, another constraint arises: due to their microscopic size, the sensitivity of the cell walls for most species, and their low culture concentrations , the downstream process is costly and difficult . There aP. palmata) and Atlantic Nori (Porphyra sp.). Successful production and domestication are, in many ways, dependent on the manipulation of different life stages and on monitoring the factors that trigger reproductive events, such as sporulation, which may result in large biomass losses [Additional challenges in seaweed production emerge, for instance, the complexity of their life cycles and domestication constraints for some of the most highly demanded species, such as Dulse [Algae\u2019s potential for human nutrition is strongly related to their biochemical composition and bioactive properties, which are known to vary widely among the different classes and even among strains. Some highlights include isolated polysaccharides, , proteins (phycobiliproteins), polyphenols , carotenoids and ic acid) . Over thic acid) ,222. OveToxicological factors also need to be considered, as algae can produce or accumulate several contaminants that impact the consumer\u2019s health. In early studies, human experiments with microalgae were scarce, and they were limited to certain countries, like Japan, the US, and Russia . It was Chlorella sp., sold as a food supplement, was found to be contaminated with anatoxin [Aphanizomenon sp., which naturally occurs in the Upper Klamath Lake, Oregon, USA, can also produce these toxins [Desmarestia sp. (Coarse Acid Kelp) is a genus that concentrates sulfuric acid in cell vacuoles and should be avoided since its consumption causes gastrointestinal problems [Coolia monotis, which produces cooliatoxin (a neurotoxin) and was detected in drifting seaweed in New Zealand [Natural toxins, such as cyanotoxins, are produced by cyanobacteria and are a common chemical contaminant in large-scale cultures . Cyanotoanatoxin , a compoanatoxin . The cyae toxins ; despitee toxins ,229. Altproblems . Another Zealand ,232.Chlorella sp., and some cyanobacteria were reported to produce a compound responsible for dermatitis and inflammations of the human respiratory system, but this is when the microalgae were in their natural form and not after being processed as a food [Algae-related food allergies are uncommon and are poorly documented, with only one clinic case documented, which was associated with Nori . Microals a food .Allergens in algae are usually associated with the environment in which they grow. Seaweeds are typically cultivated and are harvested in the open ocean or estuary environments, which are inhabited by crustaceans such as gammarids (amphipods), shrimp, and crabs (Decapoda). Commercial edible crustaceans are frequently involved in immunoglobulin E (IgE)-mediated food allergies . In a stAlthough heavy metals are not usually found in algae at values surpassing the legal limits, frequent and excessive algae consumption could pose risks that are associated with the bioaccumulation of these compounds. Heavy metal accumulation depends largely on species, as well as on environmental conditions like light, temperature, pH, salinity, or nitrogen levels ,238. ThiHizikia fusiforme, may have high levels of total and inorganic arsenic [Fucus vesiculosus, F. serratus, F. spiralis, F. evanescens, S. latissima, U. lactuca, and Cladophora sp.), there were low-level concerns regarding the presence of mercury, cadmium, and lead [In microalgae, the toxic heavy metals, arsenic, nickel, and lead, were found at very different concentrations among 10 commercial products, although at levels below the safety limits, according to the European Food Safety Authority (EFSA) . In seaw arsenic ,243. In and lead . In anotand lead . Health and lead ,245. Iodine is another common concern as it can occur in seaweed at high concentrations. Although it is essential to humans and its deficiency is a major public health challenge, excessive intake can have harmful effects, for instance, thyroid dysfunctions, goiter, and hyperthyroidism ,246,247.Mitigation strategies can be employed to minimize the risk of contamination from algae products. Water quality control is one way to avoid these problems, by minimizing the components that are adsorbed in algae . Hence, The specificity and complexity of algae contaminants are sometimes not taken into account by the current food legislation. For instance, the quantification of arsenic could be differentiated as organic and inorganic, as health risks are much lower when consuming the organic form . If thesThe processing and manipulation of the algae, such as their handling and packaging, can also be a hotspot for cross-contamination with viruses, bacteria, fungi, protozoa, organic molecules, such as prions, natural toxins, and persistent organic pollutants . The proLaminaria sp. [Biomass manipulation after harvesting could prevent the degradation of the product while ensuring a low level of contaminants. A conventional example of this manipulation is washing and boiling seaweed, as this can reduce its arsenic and iodine contents, achieving decreases of around 22% in inorganic arsenic and an almost complete reduction of iodine in aria sp. ,253,254.In the case of microalgae, boiling can have both beneficial and harmful effects. For example, boiling decreases the concentration of microcystin by 97% after 5 min , but incChlorella sp. was defined as having a strong vegetable-like flavor and aroma that would taste like powdered green tea; in the case of some dried seaweeds, they have an intense green color that could be considered limiting or off-putting when mixed in foods [Scenedesmus-based food, where the color was not well-received by testers. In France, tests on the nutritional value and customer acceptability of Spirulina-based foods concluded that algae were not very enjoyable to eat, due to their strong taste, smell, and even color [Another important factor to be highlighted regarding the introduction of algae to the market is their organoleptic characteristics, in terms of their color, odor, texture, and flavor . In termin foods ,133,136.en color . French en color .umami\u201d makes algae stand out gastronomically [kombu) [umami\u201d, for instance, a green-tea aroma and flavor in kelp species [The unique flavor of \u201comically ,267,269. [kombu) ,267. In species .The processing methods, as well as the storage conditions, could influence the flavor . NeverthFinally, and in a transversal way, a general lack of awareness and accessibility regarding algae is evidenced ,271,272.On the other hand, environmental concerns are quite different among countries; for instance, while Spanish consumers consider microalgae as being environmentally friendly, the French have contrastingly double perceptions, and the Belgians do not see this as an incentive to motivate consumption ,275,277.Over the last two decades, changes in the consumers\u2019 mindset have been happening; now, the end consumers are more informed and receptive to sustainable behaviors. This aligns with both the new and improved support policies for research projects and programs, leading to the continuous expressive growth of algae applications in the European market ,272,279.Italian consumers have a high level of willingness to eat seaweed, according to studies, given the familiarity with seaweed gastronomy in both national and Asian traditional dishes . In NordSome specific legislation and food standards entities regulate how algae can be used as food for human consumption worldwide. Usually, algae and algae-based products are regulated individually, as in the EU. The categories applied to algae are in foods including food supplements and food additives, feed and feed additives, nutraceuticals, cosmetics, packaging materials, fertilizers, biostimulants, and biofuels.In the USA, the safety of food items, including algae products, is under the regulation of the Food and Drug Administration (FDA), which grants the status of being generally recognized as safe (GRAS) to any substance that is considered to be safe for human consumption ,282. GRASimilar approaches in the regulations of novel foods are also found in Australia and New Zealand, where the Food Standards in Australia and New Zealand (FSANZ) are the entity responsible for regulating the use of new ingredients. According to FSANZ, the novel food and novel food ingredients are considered all non-traditional food and/or its derivatives requiring an assessment of the public health under the Novel Foods in the Food Standards Code. A novel food cannot be sold as food or used as a food ingredient unless expressly permitted by the Code in Standard 1.5.1 ,287.Laminaria, Gracilaria, Porphyra, Undaria, and Eucheuma have been accepted as a traditional food instead of a novel food by the Chinese for many years. Moreover, algae products could also be approved as \u201cFood for Special Medical Purposes\u201d, with a 5-year validation certificate being issued by the Center for Food Evaluation in the State Administration for the Market Regulation of China. When compared with the EU, both have established a similar system to regulate novel foods, within some common perspectives. The growth of novel food regulation in China is justified by the development of the food industries and the long-lasting food culture ,289,290.Algae, as food products in the EU, are subject to the General Food Law Regulation (EU) No. 178/2002 which is implemented in all member countries. Furthermore, the entry of novel algae species into the EU market is regulated by the Novel Food Regulation (EU), No. 2015/2283. The application procedure for authorizing the placing on the market within the EU of novel food and for updating the Union List may be found in the Official Journal of the EU (L327/1).Consumption history affects the regulatory status, meaning that the entry of novel algae species that have not been used as food in the EU before 15 May 1997 need prior authorization, to ensure their safety for human consumption. Additionally, a notification system is available to offer an easier route to the EU market for some species that have not been used in Europe but that are considered traditional foods in developing countries. This \u201ctraditional food\u201d status is given if a history of safe food use for at least 25 years can be proven. This new Regulation facilitates the introduction of new and innovative foods to the EU market, provided that specifications, such as labeling and usage conditions, are respected, thus guaranteeing food safety for European consumers.The rules enforced on algae products are regulated by Directive 2002/46/EC, which aims to protect consumers against the potential health risks associated with toxicity or misinformation. The SANCO/2006/E4/018 report assessed the use of substances, other than vitamins and minerals, with a nutritional or physiological effect in food supplements, which includes amino acids, enzymes, pre- and probiotics, essential fatty acids, botanicals , botanical extracts, and other bioactive substances. In addition, the EU delivered several reports (SEC (2008) 2976 and SEC (2008) 2977) stating that specific rules being made applicable to substances other than vitamins and minerals for use in FS are not justified. Food additives, such as preservatives, colorants, or sweeteners, which are normally used during food preparation are regulated by (EC) 1333/2008 and (EU) 231/2012 legislations. The safety of these products and the authorization assessment are carried out by the Scientific Committee on Food (SCF) and the EFSA. The concept of functional food, derived from Japan and the USA, goes beyond the nutritional and health benefits of traditional nutritional effects and differs from food supplements and nutraceuticals. Although this market is gaining extensive popularity in the last few years, the EU still lacks a regulatory framework for functional food, hindering economic competitiveness in this sector.Legislation inadequacies remain regarding the use of algae as a raw material for food. Therefore, the European Committee for Standardization (CEN) developed a technical committee for algae and algae products, including cyanobacteria and Thraustochytrids (CEN/TC 454) in 2017, which focuses on standardizing the specification, classification, terminology, algae processing, and determination methods for algae biomass, extracts or purified compounds. It is noteworthy that as these guidelines are updated, the legislation is changed accordingly.Because of limited European regulation, some EU countries are implementing their specific regulations regarding the use of algae as a food source. Non-approved algae species are being commercialized for food purposes in several European countries. For example, in 1990, France was the first European country to establish a specific regulation concerning the use of seaweed for human consumption as a non-traditional food substance, authorizing the consumption of algae for food other than what is considered to be a novel food, according to the EU ,156. TheEvidence for the consumption of more than 150 edible species of algae was identified in Europe, of which 14% are considered microalgae and cyanobacteria and 86% are considered seaweed . InteresResearch and development to mature the production process (from cultivation to packaging) have been encouraged to introduce new algae species to the market .\u22121, which are planned to decrease to EUR 0.5 kg\u22121 in the best-case scenario within the next decade [Microalgae biotechnology R&D dates back to the 19th century; since then, technologies have evolved, leading to the continuous improvement of production systems . Today, t decade . i.To increase the risk-benefit seaweed analyses, with added knowledge on the speciation of iodine/chemical form, and bioavailability;ii.To standardize and define the chemical compound classes, activities, traceability, methods, and species identification;iii.To further investigate the domestication of new species, the effects of preservation methods and treatments on biomass, and to define the best storage procedures and best practices for the evaluation of product shelf-life; andiv.To implement sensory evaluation panels .Seaweed wild harvesting is a well-established industry, and the cultivation process has been promoted . SpecifiScientists successfully brought a green fingerprint to algae as an alternative, sustainable feedstock for food and other applications , which led to an increase in the funding rate for algae-related projects within the European Union over the last few decades a.The eco-friendly image of algae industries is currently moving this sector toward larger markets, bringing with it the creation of new, skilled jobs, study programs, and economic value. Most EU projects use the green fingerprint and sustainability aspects of algae products or processes to promote a more sustainable way of living. The driving arguments for food-related algae projects and products are usually related to green consumerism. Indeed, algae technologies pose advantages compared to traditional approaches for a given application. For example, algae can be a source of food in areas where no arable lands or potable water is available and, thus, do not necessarily compete with agriculture. In addition, unsustainable fish- and soy-based lipids or proteins in food and feeds are replaceable by algae products, reducing overfishing and deforestation. This approach reduces the eutrophication and contamination of the environment and allows the recirculation of limited and valuable resources . Despite this green image, algae industries generally receive low recognition among society and decision-makers. During the Seventh Framework Program (FP7), 2007\u20132013, only ~0.5% of the EUR 44 billion of total funding was spent on algae-related projects, which was the highest percentage so far. Notably, approximately ten times more money was invested in agriculture research. Nonetheless, algae biotechnology is earning its position in the research world in Europe.n = 23) were coordinated by Spanish companies and institutions, accounting for 19% of the projects, followed by those in France (n = 19), the United Kingdom (n = 13), Germany (n = 11), and Portugal . By choosing species that are able to produce NPs, the downstream process of algae cultivation\u2014especially microalgae\u2014becomes easier and cheaper. This happens because metallic NPs have the capability to clump together, allowing a faster, cleaner, and easier separation of the algae from the culture media (2). Biological sensors made from nanoparticles are also being developed to identify the presence of hostile microorganisms. The incorporation of this technology into the cultivation of algae\u2014especially microalgae\u2014would enable a possible way of controlling the contamination of algal cultures, since this could become an accurate and fast technique by which to signal the presence of contaminants and even kill them, due to their bioactive properties .Metallic NPs have also been reported to have anti-bacterial and anti-fungal properties, especially silver and gold NP, AgNP, and AuNP, respectively . By inclWith the increase in the research for food products, an increase in the market for algae products is expected to make space for new products and brands. Algae-based products for the foods, cosmetics, and nutraceuticals markets can benefit compared to existing products, if the manufacturing companies advertise their positive properties, including the richness of their essential nutrients or the product\u2019s green fingerprint. A \u201cgreen\u201d product will drive consumers to spend more money, even if it is of lower quality or performance than a regular product ; interesThe design of algae foods is essential for market integration because algae are usually not part of Western cuisine and may have a distasteful or fishy taste and smell. Novel algae food designs are supported by EU projects. Commonly, these projects aim to position small- and medium-sized enterprises (SMEs) in the algae health food market and usually include strategies for promoting and establishing algae products in these markets. Indeed, the evolving green consumerism market serves as a stepping-stone for many companies toward the full market integration of algae foods, which is key for the movement from the development bench to the market and away from the dependency on public funding. Once established, algae products will probably spread quickly among communities via peer-to-peer influence and social norms.With legislation amendment and investment in the research and development of production systems and algae products, the algae market has the potential to grow in Europe . The ideThis review has highlighted the historical consumption of microalgae and seaweed species diversity, and their applications as foodstuffs, food supplements, and food additives in Europe. Concerns regarding establishing algae products in the market, such as production constraints , health impacts , and consumers\u2019 perceptions (acceptance and knowledge) have been addressed, as well as the legislation process followed to submit algae to the EU Novel Food Catalog. The current legislation is not broad enough for the algae sector, with specific regulations within each country and several species being produced, consumed, and commercialized beyond the approved catalog. Therefore, an update of the authorized species list is urgently required. It is evident that the algae market has strong motivations and huge potential, due to algae\u2019s nutritional and health benefits, the likelihood of sustainable production, and especially, the need to address the rise in food demand by the growing population. The development of new projects and products has been encouraged, especially regarding microalgae cultivation technology, as seaweed products are becoming more established in the global market."} +{"text": "Asian/Pacific Island Nursing Journal (APINJ). Created to fill the gap between nursing science and behavioral/social sciences, APINJ offers a forum for empirical, theoretical, and methodological issues related to Asian American and Pacific Islander ethnic and cultural values and beliefs as well as the biological and physiological phenomena that can affect nursing care. APINJ serves as a voice for nursing and other health care providers for research, education, and practice. APINJ is included in PubMed, PubMed Central, the Directory of Open Access Journals, and Scopus. As an open access journal, APINJ follows a continuous publication model, and articles are published as soon as they have been peer-reviewed and copyedited.As the editor-in-chief, I am happy to announce the launch of a new member of JMIR Publications\u2019 open access family of journals, the Nursing in Asia and the Pacific Islands comprises a rapidly growing group of professionals, and the region represents the fastest growing minority group in the United States. According to the 2020 United States census , there aAs the official journal of the Asian American / Pacific Islander Nurses Association, APINJ supports researchers, educators, and practitioners in addressing these critical information deficits by providing a quality, peer-reviewed, international forum for the exchange of knowledge in relation to Asian and Pacific Islander health and nursing care. APINJ features research papers; empirical, theoretical, and clinical articles; editorials; abstracts of recent dissertations; and conference summaries that relate to Asian American and Pacific Islander health and nursing written by those in the nursing and social sciences disciplines, such as clinical and developmental psychology, sociology, anthropology, social work, public health, education, genetics, pharmacology, infectious disease, oncology, cardiovascular disease, pulmonary function and disease, dermatology, wound healing, immunology, anesthesiology, endocrinology, gastroenterology, hematology, neonatology, nephrology, pathology, physiology, nutrition, pain management, sleep disturbances, dental health, and mental health.Building on the JMIR foundation, the scope of APINJ includes, but is not limited to, methods, interventions, instrumentation, and educational techniques; theoretical foundations that increase the understanding of underlying mechanisms for changes in health and illness; biopsychosocial, spiritual, and ecological impacts on practice, education, and research; and policy issues as a result of rigorous research outcomes.Journal of Medical Internet Research.APINJ offers authors a rapid and thorough peer-review, professional copyediting, and professional production of PDF, XHTML, and XML proofs. This journal adheres to the same quality standards as our flagship journal, the"} +{"text": "Preterm delivery complicates 5\u201313% of deliveries worldwide ,3,4,5. PIn most countries, PTD rates are increasing, and an annual estimation of 15 million babies, which equates to 11.1% of live births, are born prematurely worldwide .Spontaneous preterm parturition is a result of the pathological activation of one or more of the processes leading to delivery. The etiology of spontaneous preterm labor, which accounts for 70\u201383% of PTDs, is mostly unknown ,10, and Prevention strategies have been suggested and practiced to lower the risk of PTD; however, their effectiveness is questioned, especially among women considered to be at low risk for PTD ,14,15. TRisk factors for PTD are obstetrical, socio-economical, behavioral, environmental, and genetic, and include young or old maternal age, infertility treatments, and smoking ,17. For One of the early detectable PTD risk factors is cervical shortening or insufficiency , defined as an inability of the cervix to remain closed during pregnancy . HoweverSince PTD events are likely to re-occur in the same mother and within the family , factorsFetal development occurs throughout the entire pregnancy until full term; therefore, when PTD occurs, the newborn is not physiologically and metabolically mature, leading to immediate and long-term complications ,3,4,5. TLowering the rate of this major, relatively prevalent pregnancy complication has been declared by the WHO as \u201can urgent priority for reaching Millennium Development Goal 4, calling for the reduction of child deaths\u201d . AlthougWe would like to give special thanks to the colleagues who took part in this project for their valuable contributions."} +{"text": "In the published article, there was an error in the affiliation. Instead of \u201cSchool of Biological and Chemical Engineering, Ningbo Tech University, Ningbo, China\u201d, it should be \u201cSchool of Biological and Chemical Engineering, NingboTech University, Ningbo, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Anticholinergic syndrome (AS) is a complication that can appear due to different drugs with antimuscarinic effects, such as antihistamines, alkaloids, antipsychotics, tricyclic antidepressives or anesthetics, and it is characterized by urinary retention, dry mouth and skin, mydriasis, low-grade fever, and confusion or coma.To describe a clinical case of AS admitted to our hospital.We present a case report of a patient with schizophrenia who presented an anticholinergic syndrome. We also searched for previous studies of AS using a pubmed query.A 53-year-old male was admitted for a psychotic decompensation to another hospital in Barcelona. The usual treatment at home was amisulpride 1200mg/d, olanzapine 30mg/d and lormetazepam, and haloperidol 6mg/d and clotiapine 40mg/d were added to treat the decompensation. Then, the patient started to present mydriasis, mucocutaneous dryness, low-grade fever, slight hypertension and tachycardia, repeated retentions of urine, confusion, unintelligible speech and agitation, so he was referred to our hospital. Once he was admitted, haloperidol was withdrawn and support measures were applied. After a few days, most of the mentioned alterations were stabilized, but the psychotic symptoms, such as thought and behavioural disorganization, persisted and required electroconvulsive therapy, with subsequent improvement.AS is a relatively frequent side effect of psychiatric medication, which diagnosis is clinical, so, we must be capable to identify it and initiate early treatment to prevent possible complications. The first step, as reflected in the case described, is to stop the causative drugs, and apply support measures. Additionally, physostigmine can be used, as it is an effective antidote.No significant relationships."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cDepartment of Clinical Medicine, Shantou University Medical College, Shantou, China,\u201d it should be \u201cShantou University Medical College, Shantou, China.\u201dIn the published article, there was also an error in affiliation 2. Instead of \u201cGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Division of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China,\u201d it should be \u201cDivision of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.\u201dIn the published article, there was also an error in affiliation 3. Instead of \u201cDivision of Critical Care Medicine, Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China,\u201d it should be \u201cDivision of Geriatrics Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Over the past decade, the number of organ transplants performed worldwide has significantly increased for patients with advanced organ failure ,2,3,4,5.In this Special Issue, \u201cProgress and Recent Advances in Solid Organ Transplantation\u201d, researchers from different disciplines with different expertise and resources highlighted the novelty of their recent investigations in the field of organ transplantation, including issues related to donors, allografts, and patient survival ,18,19,20Immunosuppression management is essential for patient and graft survival in transplant recipients ,23,24, aBetter understanding of subgroups of transplant recipients, such as older transplant recipients and Black transplant recipients, can help the transplant community to identify individualized strategies to improve outcomes among these vulnerable populations ,14,28. IIn summary, the findings published in this Special Issue provide novelty and additional knowledge and may help the transplant community to ultimately improve the management and outcomes of patients with solid organ transplantation."} +{"text": "In this study, experiments were done according to the current standard methods, EPA from hemodialysis instruments. Finally, using SPSS18 software and descriptive statistics, the relationship between results at the removal of toxic, microbial, and chemical pollutants in different months and hospitals was investigated. this study showed that the average concentration of chemical characteristics during the warm season at Razi, Imam, and Golestan educational hospitals for pH, Turbidity, PO4, Cl, Mg, So4, Ca, NO2, and EC were ; ; ; ; ; , ; , and , respectively during 2018. Also, during 2019, results showed that the average levels of amounts for pH, Turbidity, PO4, Cl, Mg, So4, Ca, NO2, and EC in Razi, Imam, and Golestan educational hospitals were , , , , , , , , and , respectively. According to the results, hemodialysis instruments in Razi and Imam have a 90% efficiency in removing heterotrophic bacteria counts (HPC). Based on these findings, educational hospital hemodialysis equipment effluent in Ahvaz, Iran was mitted to Iran environmental standards for use in hemodialysis machines. The result showed that the removal percentage level of microbial and chemical pollutants by the hemodialysis process is comparatively suitable. It should be mentioned that in the proper operation and reconstruction, hemodialysis systems can have an increased rate of removal of microbial and chemical pollutants.Dialysis water is vital because of various harmful contaminants for patients. The aim of this study was to assess the efficiency of hemodialysis instruments in the removal of microbial and chemical pollutant in educational hospitals affiliated to Ahvaz Jundishapur University of medical sciences, Iran during 2018\u20132019. This cross-sectional descriptive research studied the microbial and chemical water quality of hemodialysis instruments in Razi, Sina, and Golestan hospitals in Ahwaz, Iran. 72 samples of microbial parameters and 24 samples of chemical parameters were collected from water used in hemodialysis instruments, including microbial characteristics and chemical characteristics (pH, turbidity, PO Levels of microbial and chemical pollutants in water used in hemodialysis machines have become a global problem today for patents . EnterinWater quality is important for preparation of dialysis solution due to its direct relationship with blood of patients with renal failure . HospitaThe used dialysis liquid is considered as the largest volume of water used in medicine . Water uBased on several reported studies, the main chemical agents' effects on process dialysis in hemodialysis machines include trace elements ; ionic compounds ; chemical additives to water and physiology elements \u201318. The The use of normal tap water always carries the possibility of transferring potentially toxic substances from the dialysis fluid to the patient's blood, therefore the quality of the water used to prepare the dialysis solution is very important. Because of the logical connection between water quality and the health of patients Dialysis, physicochemical and microbial quality compliance water used to prepare dialysis fluid with standards international seem necessary .Pathogenic microorganisms, disinfectants, pharmaceuticals, toxic, radioactive elements, chemicals, and microbial pollutants in water resources can all have a significant impact on human and animal health , 24. TheThe distribution network, state hospital sanitation, number of beds for dialysis, cultural situation, climatic conditions are the main agents affecting the quality and quantity of medical center water used in hemodialysis instruments , 19. EvaSurface waters are the primary source of water in Iran's southwestern region and the Khuzestan Plain . Due to the abundant resources of surface water and fertile soil, this region is one of the most strategic agricultural poles of Iran, which has a large share in the production of agricultural products . In AhvaThe high potential of Ahvaz for development and the need to equip and construct new medical centers and hospitals, increases the importance of this research. As a result, the primary goal of this study was to determine the efficacy of hemodialysis instruments in removing toxic, microbial, and chemical pollutants in the educational hospital Ahvaz Jundishapur University of Medical Sciences in southwest Iran from 2018 to 2019.4, Na, Ca, Mg, and HPC values were determined according to the standard methods . It borders Iraq on the west and the Persian Gulf on the south 38). Ah. Ah38). methods \u201345.4, Cl, Mg, So4, Ca, NO2, and EC) in educational hospital affiliated to Ahvaz Jundishapur University of medical sciences (located in south-western Iran) during 2018\u20132019 by using hemodialysis devices system which includes 2 years including 2018\u20132019.In this study, we used to assess the potential haemodialysis devices on removing the microbial characteristics and chemical characteristics , residual chlorine, sodium (flame photo meter), magnesium, calcium (titration), and sulfate (spectrophotometry method) on the efficiency of removal in sterile glass containers with a sanding head to volume 250 mL from the water inlet to hemodialysis machines. Samples of input hemodialysis devices were collected from Razi, Imam, and Golestan hospitals' dialysis departments and transferred to a laboratory for further analysis. Temperature and pH parameters were measured removal \u201348. ElecThe levels of microbial and chemical pollutants in hemodialysis instruments were collected from the three hospitals in Ahvaz city during 2018\u20132019. The coded data was entered into the SPSS software. Data analyses were performed, using SPSS-18. The data were analyzed using descriptive statistics and the mean standard deviation of the mean (SD).4, Cl, Mg, So4, Ca, NO2, and EC characteristics of the hospital hemodialysis machines , , , , , , , , and , respectively. 4, Cl, Mg, So4, Ca, NO2, and EC were , , , , , , , , and , respectively.4, Cl, Mg, So4, Ca, NO2, and EC were , , , , , , , , and , respectively , , , , , , , , and , respectively during 2018 , , , , , , , , and , respectively , , , , , , , , and , respectively during cold season , , , , , , , , and , respectively during the warm season in Razi, Imam, and Golestan hospitals during 2018 , , , , , , , , and , respectively and dialysate with particular toxicity in hemodialysis patients are raw water and municipal water, municipal water, dialysis facility, municipal water, raw water, and dialysis facility, respectively \u201354.According to different studies, the principal toxicities of chemical contaminants including copper, sulfate, chloramine, aluminum, fluoride, and nitrate are anemia , anemia , cardiovascular disease, and anemia, respectively \u201355.3, SO4, and Na shown by them . The result of their study showed that the residual chlorine and PH of water were less than the standard amount . In a siSome differences in the efficiency of hemodialysis instruments in the removal of microbial and chemical pollutants can be attributed to the quality of water supplied to water sources (surface and groundwater), the quality of water transmission and distribution network in different regions, geographical and climatic conditions in different regions of Iran or other countries, and the use of modern and up-to-date hemodialysis instruments.Different result of studies in the field of performance hemodialysis Instruments in dialysis ward at hospital and compared with our findings showed in An increasing amount of chemical and microbial pollutants can contaminate the burden of organic, microbial, chemical, and toxic pollution in the environment of the Karun river and underground sources that are fed from the Karun basin. It should be noted that the reduction of surface and groundwater quality in the region can have a direct effect on water quality in the provision of hemodialysis instruments and kidney patients referred to the dialysis wards of hospitals in Ahvaz.Any discharge of effluents and pollutants into the water supply sources of citizens and patients can greatly increase the level of dangerous and toxic pollutants that threaten the health of patients.This study investigated the performance of efficiency for hemodialysis instrument treatment in the removal of a level of microbial and chemical pollutants. Based on the results of the analysis, microbial and chemical pollutant removal during the study, had a significant direct effect on the river purification with hemodialysis instrument efficiency. Toxic, microbial, and chemical pollutants in the hemodialysis process can be very threatening to the patents. According to the results of this study, the mean value of microbial pollutants was lower than the AAMI standard value. Also, the average level of chemical pollutants was higher than the AAMI standard value. The results of this study showed that pollutants discharged into the Ahvaz Karun river are the main cause of chemical and microbial pollutants in water in this region. The results of this study showed that the health of dialysis patients, the general health of the community, and the environment are directly affected by the essential elements of bioavailability of water. Appropriate microbial and chemical water quality used in dialysis machines can be referred to the use of appropriate devices, periodic monitoring and supervision of medical engineering and environmental health experts, proper management of these devices, and the importance of managers to provide optimal services to kidney patients in the dialysis ward. The most important trends that health policymakers and experts should pay attention are updating dialysis machines with new technology, using new membrane filters with higher efficiency and using primary sources of higher quality water among. Further studies are required to assess the efficiency of hemodialysis instruments in the removal of the level of another pollutant that threatens the patents' health.The original contributions presented in the study are included in the article/HAS, ATJ, GS, ZS, AT, FK, and MJM were principal investigators of the study, drafted the manuscript, and performed the statistical analysis. HAS, ATJ, GS, and MJM were advisors of the study. All authors contributed to the design and data analysis, assisted in the preparation of the final version of the manuscript, read, and approved the final version of the manuscript.This work was funded by the grant: (ETRC-9907) from Ahvaz Jundishapur University of Medical Sciences. This study was originally approved by the Ahvaz Jundishapur University of Medical Sciences with code IR.AJUMS.REC.1399.512.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Current data suggest that SARS-CoV-2 reinfections are rare. Uncertainties remain, however, on the duration of the natural immunity, its protection against Omicron variant, and on the impact of vaccination to reduce reinfection rates. In this retrospective cohort analysis of the entire population of an Italian region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-February 2022). After an average of 277 days, we recorded 729 reinfections among 119,266 previously infected subjects , eight COVID-19-related hospitalizations , and two deaths. Importantly, the incidence of reinfection did not vary substantially over time: after 18\u201322 months from the primary infection, the reinfection rate was still 6.7\u2030, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among females, unvaccinated subjects, and during the Omicron wave. After the first documented case in August 2020 in Hong Kong , a numbeWe included all residents in the Abruzzo Region, Italy with \u22651 positive nasopharyngeal swab detected through RT-PCR by the regional-accredited laboratories, from the start of the pandemic up to January 4, 2022. On February 18, 2022 , we extracted all data of the official vaccination , COVID-19 (\u201cSurveillance COVID-19 Platform\u201d), demographic , hospital , and co-pay exemption datasets of the National Healthcare System, merging individual information through encrypted fiscal code was used for all analyses.The proportion of reinfections was computed in the total sample, and by demographic and clinical characteristics, time after primary infection , and predominant circulating variant . Cox proportional hazard analysis was then used to compute the relative hazards of reinfection, after adjusting for age, gender, vaccine status , severe COVID-19 after the first infection, and comorbidities, all included From the start of the pandemic, a total of 251,047 infections were detected among the 1,293,941 residents in the Abruzzo Region. After the exclusions of the subjects with a follow-up <45 days, or lacking negative intermediate swabs, a total of 119,266 subjects with primary infection were included in the analysis. The average time after the primary infection was 277 days ; 3,001 subjects had a follow-up longer than 18 months .Overall, the incidence of reinfection was 6.1\u2030 (n = 729). Eight subjects were hospitalized due to COVID-19 , and two died .n = 613; 11.4 per day) than during the 317 days of the pre-Omicron period . In contrast, the incidence of reinfection did not vary substantially by baseline comorbidities and over time: after 18 or more months from the primary infection (up to 22 months), the reinfection rate was still 6.7\u2030. The multivariable analysis confirmed univariate results . The Ethics Committee waived the requirement of written informed consent for participation.MF, GS, CAM, and LM: concept and design. GS, GDM, RC, and LM: acquisition, analysis, or interpretation of data. MF, CAM, and LM: drafting of the manuscript. GS, GDM, AC, and LM: critical revision of the manuscript for important intellectual content. MF and LM: statistical analysis. GS, GDM, RC, and AC: administrative, technical, or material support. AC and LM: supervision. LM: had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Background: Equity, equality, diversity, and inclusion are terms covered in the academic literature focusing on sports, kinesiology, physical education, and physical activity, including in conjunction with marginalized groups. Universities in many countries use various EDI policy frameworks and work under the EDI headers \u201cequality, diversity and inclusion\u201d, \u201cequity, diversity and inclusion\u201d, \u201cdiversity, equity and inclusion\u201d, and similar phrases to rectify problems students, non-academic staff, and academic staff from marginalized groups, such as women, Indigenous peoples, visible/racialized minorities, disabled people, and Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, and Two-Spirit (LGBTQ2S+) experience. Which EDI data, if any, are generated influences EDI efforts in universities of all programs. Method: Our study used a scoping review approach and employed SCOPUS and the 70 databases of EBSCO-Host, which includes SportDiscus, as sources aimed to analyze the extent (and how) the academic literature focusing on sports, kinesiology, physical education, and physical activity engages with EDI. Results: We found only 18 relevant sources and a low to no coverage of marginalized groups linked to EDI, namely racialized minorities (12), women (6), LGBTQ2S+ (5), disabled people (2), and Indigenous peoples (0). Conclusions: Our findings suggest a gap in the academic inquiry and huge opportunities. Many different EDI-related phrases, such as \u201cequity, diversity and inclusion\u201d, \u201cdiversity, equity and inclusion\u201d, and others ,20,21,22Many different EDI-related phrases have been generated in recent years, such as equity, diversity, and inclusion ; equalitWork performed under these EDI frameworks and EDI phrases are envisioned to lead to systemic positive change for students, academic staff, and non-academic staff in universities as a workplace, in general, but also in the research and education reality . Althoug\u201cDimensions: equity, diversity and inclusion Canada invites you to take part in a post-secondary transformation to increase equity, diversity and inclusion (EDI) and help drive deeper cultural change within the research ecosystem\u201d . \u201cThe DiHowever, many problems have been identified, in relation to EDI implementations .Studies focusing on sports engage with equity and equality, in the context of the EDI groups of gender ,40,41,42Studies focusing on kinesiology engage with equity and equality, in the context of the EDI groups of gender ,84,85,86Studies focusing on physical education engage with equity and equality, in the context of the EDI groups of gender ,100, racStudies focusing on physical activity discuss equity and equality, in the context of the EDI groups of gender , race 1,124,125,UN Convention on the Rights of Persons with Disabilities flags access to recreation, leisure, and sport in their daily life, including schools [The schools , as a pr schools ,141,142. schools , differe schools , and ben schools . Nationa schools (p. 291) schools . These p schools , and it schools . Many pr schools . Problem schools (p. 71), schools . Accordi schools (p. 91). schools , non-dis schools , diversi schools , more ha schools (p. 225) schools (p. 225)Disabled activists and academics coined the term ableism in the United States and Britain during the 1960s and 1970s to flag the cultural reality of ability-based expectations, judgments, norms, and conflicts. Many worked, and work is ongoing on the disabling and enabling use of ability expectations and ableism ,175,176,Ableism is also used to call out ability-based discriminations against disabled people within the kinesiology, sport, physical education, and physical education literature ,193,194,As to physical education, instructional ableism and microaggressions is flagged as a problem , and it Regarding sports, it is argued that ableism impacts social practice within sports, and ableism in sports has to be addressed ,195. It Many studies cover individual EDI terms that make up the various EDI phrases in the context of sports, kinesiology, physical education, and physical activity. However, to our knowledge, no study has, so far, analyzed whether the academic literature also engages with the existing EDI phrases and frameworks. That is important to know because EDI phrases and frameworks are linked to specific policy endeavors in the workplace, such as universities. How these policies are implemented impacts the research and education activities of and day-to-day operations in the fields of sports, kinesiology, physical education, and physical activity. Our study aims to fill the gap and investigate to what extent (and how) the academic literature focusing on sports, kinesiology, physical education, and physical activity engages with existing EDI phrases and frameworks. Given that specific marginalized groups are the focus of the activities performed under the EDI phrases and frameworks, our study also investigated which marginalized groups are mentioned.Scoping studies are useful in identifying the research that exists on a subject ,199. OurOur study employed a modified version of a scoping review outlined by Arksey and O\u2019Malley , as perfWe searched, on 22\u201326 May 2021 , the 70 databases accessible through EBSCO-Host, which includes CINAHL, SportDiscus, and Scopus (which incorporates the full Medline database collection) for English language data with no time restrictions, accessing journals that cover relevant content to our research questions. We searched for scholarly peer-reviewed journal articles in EBSCO-Host, and we searched for reviews, peer-reviewed articles, conference papers, and editorials in Scopus. We performed the following search strategies .To answer the research questions, we first obtained hit counts for our search term combinations , employiAs to trustworthiness measures ,208,209,The search strategies generated 26 abstracts, of which 18 were deemed to have relevant content. The full texts of the 18 relevant abstracts were downloaded and thematically analyzed . (a)The first one being academic/educational setting, but not university, which was classified as anything that is related to academics setting; for example, research conferences that are open to all fields of studies and careers, K to 12 education, and other academic organizations.(b)Non-academic settings, which primarily looked at sport facilities and organizations, recreational facilities and organizations, and general physical activity.(c)University setting, consisting of discussions around different university institutions and, specifically, different areas of the faculty of kinesiology.We present the themes in the downloaded full text articles in three sections:We separated the findings further by the following four areas: physical education, sport, physical activity, and kinesiology.Furthermore, we separate the findings into the four common themes we found: (a) EDI recommendation/EDI needs, (b) EDI curriculum and teacher/educator/mentor role in EDI, (c) EDI literacy/EDI narrative, and, lastly, (d) EDI study results.Finally, we separated the results according to which EDI group they looked at. If a source did not specifically discuss equity deserving groups, it was labelled as \u201cno group\u201d.In each of the results sections, we first provide the frequency counts for the presence of themes we found. We only list where there was at least one hit for the theme. The themes that had 0 results are not listed in the tables.-0 results on physical education, in terms of EDI study results;-0 results on sport, in terms of EDI curriculum and educators and mentor\u2019s role in EDI;-0 results on physical activity, in terms of EDI recommendations/EDI needs;-0 results on physical activity, in terms of EDI curriculum and educators and mentor\u2019s role in EDI;-0 results on physical activity, in terms of EDI literacy/EDI narrative;-0 results on physical activity, in terms of EDI study result;-0 results on kinesiology, in terms of ALL the EDI-related themes.Within the academic/educational setting theme, the following themes returned no results and, as such, are neither listed in There were twelve findings, in a total of five sources, that discussed EDI recommendations/EDI needs, in the context of physical education in an academic setting. Out of the twelve findings, one of them discussed persons with disabilities, three of them discussed ethnic groups, and eight of them did not cover any specific EDI group.The Recreational Sports Journal, and found that EDI was not discussed in a meaningful way during the time period of their study; it is very important to address this void and publish more papers that cover EDI topics [The EDI recommendation related to persons with disability(s) in physical education settings was that regular contact with non-disabled children in physical education classes aids in the inclusion of those with disabilities in society . The EDII topics . It was I topics .There were nine findings, in a total of three sources, that discussed EDI curricula and the teachers/educator/mentor role in EDI, in the context of physical education in an academic setting. Out of the nine findings, one of them discussed ethnic groups and the other eight covered no specific EDI group. In terms of ethnic groups, it was discussed that taking the initiative to build EDI curricula brings the opportunity to include more culturally responsive and cultural enrichment pedagogy . The folJournal of Sport Rehabilitation for their commitment to diversity, equity, and inclusion [There were three findings, out of a total of one source, that discussed EDI recommendation/EDI needs, in the context of sports in an academic setting. Out of those three findings, none of them covered a specific EDI group. The source was a statement that was put out by the nclusion . In the nclusion . They stnclusion . They funclusion .The following source discusses reflections that occurred at EDI conferences . This soRecreational Sports Journal [Recreational Sports Journal articles that were analyzed, 18% addressed at least one equity diversity and/or inclusion issues [There were seven findings, out of a total of two sources, that discussed EDI study results, in the context of sports in an academic setting. One of the sources covered all EDI groups, whereas the other source did not cover any EDI groups. The first source was a content analysis of equity, diversity, and inclusion in the Journal , perform Journal . In this Journal . It is i Journal . This con issues . Furthern issues . The secn issues . In thisn issues . It was n issues .-0 results on physical education, in terms of all the EDI-related themes;-0 results on sports, in terms of EDI curriculum and educator/mentor\u2019s role in EDI;-0 results on sports, in terms of EDI literacy/EDI narrative;-0 results on physical activity, in terms of EDI curriculum and educators/mentor\u2019s role in EDI;-0 results on physical activity, in terms of EDI literacy/EDI narrative;-0 results on physical activity, in terms of EDI study results;-0 results on kinesiology, in terms of ALL the EDI-related themes.Within the non-academic setting theme, the following returned no results and, as such, are neither listed in There was one finding, through one source, that discussed EDI recommendations/EDI needs in the context of physical activity in a non-academic setting. This EDI recommendation/EDI need did not cover any specific EDI group. It was discussed that there is an \u201curgent need\u201d to address EDI within intramural and recreational sports . This reThere were five findings, in a total of four sources, that discussed EDI recommendations/EDI needs in the context of sport in a non-academic setting. Out of those five findings, one discussed women and ethnic groups, one discussed ethnic groups, and two discussed no EDI groups. The EDI recommendation and need to promote racial EDI within black women\u2019s football in Brazil were highlighted . This reThere were eight findings, out of a total of three sources, that presented EDI study results in the context of support in a non-academic setting. Out of the eight findings, four discussed LGBTQIA+ topics, two discussed women, one discussed ethnic groups, and one discussed both women and ethnic groups. One EDI study result discussing LGBTQIA+ was that athletes have a fear of disclosing their sexuality or sexual orientation, in fear of discrimination from the sports industry . Because-0 results on physical education, in terms of ALL the EDI-related themes;-0 results on sports, in terms of EDI curriculum and educator/mentor\u2019s role in EDI;-0 results on sports, in terms of EDI literacy/EDI narrative;-0 results on sports, in terms of EDI study result;-0 results on physical activity, in terms of ALL the EDI-related themes;-0 results on kinesiology, in terms of EDI curriculum and Educators/mentors role;-0 results on kinesiology, in terms of EDI/EDI narrative.Within the university setting theme, the following returned no results and, as such, are neither listed in There were four findings, in a total of two sources, that discussed EDI recommendation/EDI needs in the context of sport in a university setting. Out of those four findings, none of them discussed a specific EDI group. One of the findings presented the recommendation that, for the future of college recreational sports programs, those programs have a responsibility to address the needs of the changing demographic interests, as well as the diverse students on campus . This soThe recommendation in this one source addressed that the kinesiology program design can use student narratives and experiences to make the shift from neutral documents and pedagogy to ones that expose and work towards dismantling Eurocentricity within the field of study .The objective of this study was to ascertain to what extent (and how) the academic literature focusing on sports, kinesiology, physical education, and physical activity engages with the various EDI phrases and frameworks, as well as which of the marginalized groups covered under EDI are mentioned in the literature covered.We found only 18 relevant hits with all our search strategies, whereby the EDI frameworks were not at all found. Only \u2018sport*\u2019 generated any hits related to EDI phrases; the other three fields did not. The majority of our findings were based on the presence of all the individual EDI terms, but not as phrases; within these sources, the term \u201csport*\u201d was the most linked to EDI, with much less physical activity or physical education and even less kinesiology. On top, we found a very low to no coverage of marginalized groups normally linked to EDI, namely racialized minorities (12), women (6), LGBTQ2S+ (5), disabled people (2), and Indigenous peoples (0), within the already low coverage of EDI.Altogether, our findings suggest a huge gap in the academic inquiry and huge opportunities for research on EDI within sports, physical education, physical activity, and kinesiology by themselves, but also in collaborations with many other fields and groups, such as disability studies and other identity group studies, social justice studies, education, media studies, global south focused studies, sustainability studies, socially disadvantaged groups, practitioners, and policy makers. Given that ableism is employed in the academic literature covering sports, physical education, physical activity, and kinesiology, we especially see opportunities for sports, physical education, physical activity, and kinesiology academic efforts to use the ableism lens to enrich the EDI discourses. For the remainder of the section, we discuss the problems of our findings, using as lenses: (a) the academic literature related to physical education, sport, physical activity, and kinesiology, individually covering the terms equity, equality, inclusion, and diversity; (b) the premise of the EDI frameworks and phrases, in general, as well as in the context of disabled people; and (c) ableism experienced by disabled people, but also beyond.Efforts performed under the EDI frameworks and EDI policy terms are envisioned to lead to systemic positive change for students, academic staff, and non-academic staff in universities, as a workplace, in general, but also in the research and education reality in universities ,34,35,36Given this sweeping mandate for positive systemic and cultural changes EDI actions are to engender, much more should have been found in our searches that link sports, physical education, physical activity, and kinesiology to EDI policy frameworks and phrases with particular emphasis on the EDI targeted groups. However, our findings are not surprising, as the EDI frameworks and phrases are rarely visible in other contexts either, such as disabled people, in general . HoweverIn sports, physical education, physical activity, and kinesiology, the individual terms of equity, equality, diversity, and inclusion are discussed, in the context of the EDI groups of gender, race, LGBTQ2S+ ,125,126,Ableism is a term coined by disabled activists and academics to flag the cultural reality of ability-based expectations, judgments, norms, and conflicts ,175,176.The cultural reality of ableism is intersectional ,180,181.The search was limited to two academic databases and English language literature. As such, the findings are not to be generalized to the whole academic literature, non-academic literature, or non-English literature. These findings, however, allow conclusions to be made, within the parameters of the searches.The low hits we obtained in our scoping review suggests a gap in academic inquiry around EDI and sports, physical education, physical activity, and kinesiology. Many research projects could evaluate the existing EDI frameworks and EDI phrases, through the lens of sports, physical education, physical activity, and kinesiology. One could answer the following research questions: What do the EDI phrases mean for sports, physical education, physical activity, and kinesiology? Which phrases are the most suitable for sports, physical education, physical activity, and kinesiology? Do words have to be added to the phrases? Why has the academic literature in sports, physical education, physical activity, and kinesiology not engaged with the phrases and frameworks yet? What are the societal consequences of sports, physical education, physical activity, and kinesiology not generating academic data and engaging with the EDI frameworks and phrases? Answers to these questions can be obtained conceptually for sports, physical education, physical activity, and kinesiology, with surveys and interviews covering EDI-deserving groups on the level of students, academic staff, and non-academic staff. This research can engage with workplace climate, education, and research realities. For example, in a 2019 Statistics Canada survey, it is stated that 35% of disabled university professors, instructors, teachers, or researchers \u201cexperienced unfair treatment or discrimination in the past 12 months\u201d, and 47% saw themselves \u201csubjected to at least one type of harassment in the past 12 months\u201d . Within"} +{"text": "Dear Editor,Dracocephalum kotschyi and Trachyspermum ammi\u2019 by Zarei-Yazdeli et al. (T. ammi seed extract (TASE) inhibited some pathogenic microorganisms such as Pseudomonas aeruginosa, Shigella dysenteriae, Escherichia coli and Staphylococcus aureus. The paper stated that seed extract from this plant can be considered as a phytochemical preservative in the food industry in the future. However, whilst there are some studies about TASE, it seems to me that the studies relating to the extraction process, biological effects and chemical components of this material are still insufficient.I read with interest the manuscript titled \u2018Evaluation of antibacterial synergism of methanolic extract of i et al. , in whicT. ammi is commonly known as ajwain or ajowan. All parts of this plant can be used in medicine, especially the seeds, which contains carbohydrates, fibre, tannins, glycosides, protein, fat, saponins, flavones and minerals while the essential oil (EO) of the seeds possesses a large amount of precious components, including \u03b3-terpinene, p-cymene and thymol. This material has many medical applications, such as antifungal, antioxidant, antimicrobial, antinociceptive, cytotoxic, hypolipidemic, antihypertensive, antispasmodic, broncho-dilating actions, antilithiasis, diuretic, abortifacient, antitussive, nematicidal, anthelmintic and antifilarial ratios are different in all studies, ranging from 1/10 to 3/10 (g/mL) , 3, 6, w species , althoug species , 9. ThisThere are no official standards and published reports on the specific chemical compounds (non-volatile compounds) that exist in TASE. In my opinion, non-volatile compounds such as phenolic acids, saponins, alkaloids or flavonoids are also extremely important for the bioactivity of the extract. We can completely determine these compounds by high-performance liquid chromatography (HPLC); however, this method is quite complex and costly and needs many different standard substances to screen and identify the chemical components. Therefore, in my opinion, finding new or precious compounds in TASE by HPLC is very interesting and necessary, as this will help us to clarify the roles of the bioactive compounds.In general, the bioactivity of TASE strongly depends on the extraction conditions and chemical components. I believe that we still have the space to study some issues related to this material and that the scientific results obtained will be very valuable as they will enhance our knowledge, which can be widely applied in the pharmaceutical and medical fields."} +{"text": "Chimeric antigen receptor (CAR) T cell therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma and is associated with unique toxicities, in particular cytokine release syndrome (CRS) and neurotoxicity/immune effector cell\u2010associated encephalopathy syndrome (ICANS) , 2, 3. TA 28\u2010year old woman with refractory primary mediastinal B cell lymphoma was referred for standard of care (SOC) CAR T cell therapy after receiving R\u2010CHOP chemotherapy, radiation, and GDP salvage chemotherapy. Due to tumor burden with extensive abdominal involvement, she received bridging therapy with pembrolizumab, dexamethasone, and radiation to the right kidney for presumed transverse myelitis but returned on D+33 with worsening ascending numbness, bilateral leg weakness, and urinary retention Figure\u00a0. On examOver the next 4 months, the patient regained some motor strength in the lower limbs and reported improvement in sensory symptoms . Follow\u2010up imaging of the spine on D+208 showed significant improvement in cord signal change from T1 \u2010 T6 with resolution of enhancement disruption which may facilitate the influx of cytokines, recruitment of monocytes, and activation of macrophages, but elevated levels of the excitatory N\u2010methyl\u2010D\u2010aspartate receptor agonists glutamate and quinolinic acid have also been described , 9, 17.Risk factors associated with the development of neurotoxicity include patient\u2010related factors such as younger age, higher tumor burden, and a history of early and/or high\u2010grade CRS, as well as product\u2010related characteristics such as CAR design and choice of lymphodepletion regimen , 5, 6. OOne limitation of this case report is that in the SOC setting CAR T cells are not routinely quantified or phenotyped, and, therefore, we could not determine if there were any CAR T cell characteristics that differed in this case, and neither was it possible to determine the presence of CAR T cells in the CSF. The patients who developed leukoencephalopathy in the case report from ZUMA\u20101, for example, were found to have a massive expansion of peripheral CAR T cells and prominent features of BBB disruption .Interestingly, it is also unclear whether any of the treatments pursued changed the disease course or whether time alone leads to disease improvement in such cases. Rituximab was not administered as CD19 CAR T cell therapy strongly depletes B cells, and additional B cell depletion was considered unlikely to be of benefit.As a relatively new technology, rare and unexpected side effects may occur in patients receiving CAR T cell therapy. Reporting and collection of such cases will help to increase awareness of rare presentations and advance the expertise in managing these challenging cases.SS, SM, JAS, KR, NF, DW: No disclosures. RF: Research funding from Novartis and Kite. MLD: Research funding from Celgene, Novartis, Kite, and Atara; other financial support from Novartis, Precision Biosciences, Celyad, Bellicum, and GlaxoSmithKline; stock options from Precision Biosciences, Adaptive Biotechnologies, and Anixa Biosciences. FLL: Scientific advisory role with Kite, a Gilead Company, Novartis, Celgene/Bristol\u2010Myers Squibb, GammaDelta Therapeutics, Wugen, Amgen, Calibr, and Allogene; consultant with grant options for Cellular Biomedicine Group, Inc.; research support from Kite, a Gilead Company. MDJ: Consultancy/advisory role for Kite/Gilead, Novartis, Takeda, and BMS. JGK: Consultant or advisory role for Abbvie, BMS, Gilead, Karyopharm, Merck, Roche, Seattle Genetics; honoraria from Amgen, Antengene, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics, TG Therapeutics; research funding from Canadian Cancer Society, Leukemia and Lymphoma Society Canada, Princess Margaret Cancer Foundation, Janssen, Roche, Astra Zeneca; other remuneration from Karyopharm (DSMB).KR and RF performed cytokine and data analyses and reviewed the manuscript; JAS, MLD, NF, and FLL critically reviewed and edited the manuscript; SS, MDJ, DW, and JGK analyzed data and wrote and edited the manuscript."} +{"text": "Data science, information theory, probability theory, statistical learning, statistical signal processing, and other related disciplines greatly benefit from non-negative measures of dissimilarity between pairs of probability measures. These are known as divergence measures, and exploring their mathematical foundations and diverse applications is of significant interest , and itvergence ,13. The i-Silvey , Csisz\u00e1ri-Silvey ,16,17, ai-Silvey , is a usf-divergences. The latter implies, in particular, that the Jensen\u2013Shannon divergence satisfies data-processing inequalities. The first paper in this Special Issue [Relative entropy is a well-known asymmetric and unbounded divergence measure , whereasal Issue , authoreal Issue further Many of Shannon\u2019s information measures appear naturally in the context of horse gambling, when the gambler\u2019s utility function is the expected log-wealth. The second paper , coauthof-divergences. The third paper [f-divergences. Applications that are studied in [The relative entropy and the rd paper , by Nishudied in include The interesting interplay between inequalities and information theory has a rich history, with notable examples that include the relationship between the Brunn\u2013Minkowski inequality and the entropy power inequality, transportation-cost inequalities and their tight connections to information theory, logarithmic Sobolev inequalities and the entropy method, inequalities for matrices obtained from the nonnegativity of relative entropy, connections between information inequalities and finite groups, combinatorics, and other fields of mathematics . These properties lead to f-divergence inequalities, and to information-theoretic applications strongly convex divergence dominates the square of the total variation, which extends the classical bound provided by the chi-squared divergence. Its analysis also yields improvements of Bayes risk f-divergence inequalities, consequently achieving a sharpening of Pinsker\u2019s inequality.Basic properties of an e, e.g., ,35,36,37e, e.g., ,40,41,42e, e.g., , authoref-divergences, which contains most of the classical inferential tools, and which is indexed by a single scalar parameter. This class belongs to the family of f-divergences, and is usually referred to as the power divergence class, which has been considered by Cressie and Read [Divergences between probability measures are often used in statistics and data science in order to perform inference under models of various types. The corresponding methods extend the likelihood paradigm, and suggest inference in settings of minimum distance or minimum divergence, while allowing some tradeoff between efficiency and robustness. The sixth paper , authoreand Read ,45. The and Read states tThe seventh paper by Verd\u00fa is a reslarly to (the seclarly to , it is wlarly to . In the larly to , the thistudy in . Furtherstudy in closes tstraints ,49, by mf-divergence measures are considered. The optimal design of the linear transformation of the data onto a lower-dimensional subspace is characterized for zero-mean Gaussian models, and numerical algorithms are employed to find the design for general Gaussian models with non-zero means.In statistical inference, the information-theoretic performance limits can often be expressed in terms of a statistical divergence measure between the underlying statistical models (see, e.g., and refeIt is our hope that the reader will find interest in the eight original contributions of this Special Issue, and that these works will stimulate further research in the study of the mathematical foundations and applications of divergence measures."} +{"text": "N-nitroso compounds (NOCs) are a class of chemical carcinogens found in various environmental sources such as food, drinking water, cigarette smoke, the work environment, and the indoor air population. We conducted a systematic review and meta-analysis to investigate the links between nitrate, nitrite, and NOCs in food and water and the risk of gastrointestinal (GI) cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). A systematic search of the literature in Scopus, PubMed, Google Scholar, Web of Science, ScienceDirect, and Embase was performed for studies on the association between NOCs in drinking water and food sources and GI cancers. Forest plots of relative risk (RR) were constructed for all the cancer sites and the intake sources. The random-effects model was used to assess the heterogeneity between studies. Forty articles were included after removing duplicate and irrelevant articles. The meta-analysis indicated that the intake of high dose vs. low dose of these compounds was significantly associated with the overall GI cancer risk and nitrite , and N-nitrosodimethylamine (NDMA) . We found that dietary nitrite intake increased GC , and EC . Additionally, dietary NDMA intake increased the risk of CRC . This meta-analysis provides some evidence that the intake of dietary and water nitrate, nitrite, and NOCs may be associated with GI cancers. In particular, dietary nitrite is linked to GC and EC risks and dietary NDMA intake is associated with CRC. In 2020, cancer accounted for nearly 10 million deaths and nearly one in six deaths worldwide. Gastrointestinal (GI) cancers, with an estimation of approximately 5 million new cases and 3.5 million deaths worldwide, accounted for half of the cancer burden in 2020 [H pylori infection, high body mass index, low physical activity, and dietary factors [In addition to non-modifiable risk factors such as the demographic characteristics, family history, and genetic predisposition, some preventable risk factors are well established for GI cancer, including tobacco smoking, alcohol consumption, factors ,4,5,6.The N-nitroso compounds (NOCs) are a broad class of chemical carcinogens that exist in various environmental sources such as food, drinking water, cigarette smoke, the work environment, and the indoor air population, although intrinsic sources are also available for crucial needs of our bodies ,10,11,12Several experimental and epidemiological studies have shown that nitrate, nitrite and NDMA can affect human health , includiThe online database searches were performed in January 2022. Searches were undertaken for English-language peer-reviewed publications on the association of nitrate, nitrite, and NOCs and the risk of GI cancers between 1990 to the present. The databases included Scopus, PubMed, Google Scholar, Web of Science, ScienceDirect, and Embase. The search strategy was designed using MeSH terms like \u201cGastrointestinal Cancers\u201d, \u201cDigestive System Cancers\u201d, \u201cOrganic Chemicals\u201d, \u201cNitroso Compounds\u201d, \u201cNitrate\u201d, \u201cNitrite\u201d,\u201dNDMA\u201d, and \u201cEpidemiologic Studies\u201d. Based on our searches on the databases, a total of 12,750 articles were retrieved, including 4539 articles for GC, 2204 for EC, 6673 for CRC, and 2243 for PC. A total of 40 studies were included after the title, abstract, full-text evaluations, and quality assessment ,60,61,62The study screening and quality assessment were conducted by three researchers , and in the event of any discrepancies, a referee (EM) intervened. The data extraction file contained the demographic characteristics of the article such as the author\u2019s name, the year of publication, the title, the type of study, the country, as well as the design characteristics, including the sample size, the sampling method, the source of the population, the type of controls, the type of cancer, the source of nitrate, nitrite, and the NOCs , and the method of data collection . Finally, the effect size measures, including the relative risks (RRs) for the cohort studies and the odds ratios (ORs) for the case-control studies and their 95% CI were abstracted.Quality assessment of the included articles (case-control or cohort studies) was accomplished using the Newcastle-Ottawa Scale (NOS) . For cas2 statistic [2 > 60%), was estimated using a random-effects model [p-value of heterogeneity was assessed using a sub meta-analysis. Moreover, publication bias was examined by creating a funnel plot and a regression asymmetry test [The relationships between nitrite, nitrate, or NMDA intake and the risk of GI cancers were examined based on the effect size measurements and the corresponding 95% CIs of each study. Because of the rare disease assumption, the ORs are assumed to approximate the RRs . Heteroggeneity) . The poots model . All anatry test ,69.A total of 40 independent studies were included in the meta-analysis, including 27 case-control studies ,57,60,61The meta-analysis was repeated for each cancer site based on the nitrate, nitrite, NDMA and the source intake.2 = 80.2%, P-heterogeneity = 0.025), the food intake of nitrate , and the food intake of nitrite . There were no statistically significant excess risks from the food sources of nitrate, NDMA, or the water sources of nitrate intake. We observed significant heterogeneity for studies of the food sources of NDMA (I= 0.004) . There w= 0.004) .2 = 92.2%, P-heterogeneity = 0.000). Additionally, there were significant heterogeneities for studies of the food intake of NDMA , the food intake of nitrate , and the water intake of nitrate (I= 0.000) . We foun= 0.000) .2 = 73.4%, P-heterogeneity = 0.002), the food nitrite intake , and the water intake of nitrate . No statistically significant heterogeneity across studies was observed for CRC in relation to NDMA intake, but heterogeneity was statistically significant for studies of the food nitrate intake (I= 0.000) . Stratif= 0.000) .2 = 80.7%, P-heterogeneity = 0.000), and nitrite . No sign= 0.000) .We found limited high-quality research on nitrate, nitrite, NOCs, and cancer risk, most likely due to the difficulty of quantifying these compounds from different sources worldwide. Despite this limitation, the literature suggests that dietary and water sources may be risk factors for GI cancers, in particular, nitrate intake from water sources and diet for CRC, nitrite intake from diet for GC, and NDMA intake for CRC and EC ,56,59,70Nitrate and nitrite as precursors of the NOCs are suspected of playing a key role in cancer carcinogenesis through the induction of DNA-damaging metabolites, like aldehydes and alkyldiazonium ions, which could cause cancerous lesions in cells ,16,58,70H pylori infection in the GC studies [There was heterogeneity in the study designs and the methodologies, which may explain the differences in the results of the published studies. The high heterogeneity observed in our meta-analyses may be due to the variety of confounders used in the models as well as the differences between the study settings, the population characteristics, the compound ranges, and the estimation methods. Except for age and gender, other confounders were less consistently controlled for, particularly dietary factors and specific risk factors, such as studies .The number of reviews for EC was limited. A meta-analysis study by Lie et al. in 2016 H.pylori infection may increase the NOCs product level and increase the risk of GC [In 2016, Lie and others found an inverse association between dietary nitrate consumption and GC, and a borderline association between dietary nitrite consumption and GC . In 2015sk of GC .Previous studies on association between the NOCs and CRC are inconsistent. In 2016, one systematic review reported that dietary nitrite/nitrate intake was not significantly linked with CRC , howeverNone of the previous reviews reported a significant relationship between dietary or water intake of nitrate, nitrite, and NDMA and the risk of PC ,19. Our The geographical distribution of the studies plays an important role in achieving reliable results. A majority of the studies included in our review were conducted in Europe (30%) and North America (48%), and we found no reliable studies from low- and middle-income countries (LMICs). As a result, our findings cannot be generalized to LMICs, where the amounts of nitrate, nitrite, and NOCs may vary based on the dietary patterns, the cooking methods, the water sources, the effect of seasonal rainfall on water compounds, and the fertilizer compounds . Also, mIn conclusion, our meta-analysis shows modest evidence on the association between dietary and water nitrate, nitrite, and NOCs intake and certain types of GI cancer risk. The dietary intake of nitrite is associated with GS and EC and the dietary NDMA intake is associated with CRC. In future studies, the influence of different compound types on cancer should be explored by considering the source intake, and gender differences, particularly in less studied geographical regions."} +{"text": "At present, \u201cBelt and Road\u201d (\u201cB&R\u201d) member states (accounting for about 61.78% of the world\u2019s population) face different types of cancer threats to varying degrees. We analyzed the incidence and mortality and risk factors of cancer in the member countries of the \u201cB&R\u201d to explore the basis of health and medical cooperation between countries and provide a foundation for formulating cancer prevention and control policies for building a healthy \"B&R.\"Data were derived from the Global Cancer Observatory and Cancer Country Profiles in 2020. Incidence and mortality were age-standardized rates (ASRs). Population attributable fractions (PAFs) was applied to measure risk factors of cancers in the \u201cB&R\u201d countries. The mortality\u00adto\u00adincidence ratio (MIR) was calculated by dividing the mortality rate by the incidence rate.A total of 26 cancers were included in the study. Lung, breast, colorectal, stomach, liver, prostate, cervical, esophageal, thyroid, and uterine cancers were the most common and highest in age-standardized mortality in the \u201cB&R\u201d countries. For men, Hungary had the highest cancer age-standardized incidence and mortality , followed by Latvia . In females, the highest incidence rates were estimated in Greece , and the highest mortality rate was Brunei . All countries were in the middle or high HDI range, with about half (46.88%) of countries achieving high HDI, mostly in Central and Eastern Europe (13 countries) and West Asia (10 countries). The United Arab Emirates had the highest MIR in male and female (1.59 vs 2.19). Tobacco products, infectious factors, and ultraviolet rays were the three main cancer risk factors in the \u201cB&R\u201d countries.The overall burden of cancer in the countries along the \u201cB&R\u201d remains substantial, while the corresponding cancer prevention and control policies need to be improved. Strengthening health cooperation among member countries will contribute to a joint response to the risks and challenges posed by cancer.The online version contains supplementary material available at 10.1186/s12885-022-09657-3. More than 2,000 years ago, people on the Eurasian continent explored many trade and cultural exchange routes that connected the major civilizations of Asia, Europe, and Africa, and later generations collectively referred to these routes as the \"Silk Road\" . During In recent years, with the development of society and the economy, the disease burden in low\u2013human development index (HDI) and medium-HDI countries has shifted from being dominated by communicable, maternal, neonatal, and nutritional diseases (CMNNDS) to being dominated by non-communicable diseases (NCDs) and injuries . With thhttps://www.who.int/countries) [We used data from the Global Cancer Observatory (gco.iarc.fr) and Cancuntries) in 2020.untries) .\"B&R\" initiative refers to the cooperative organization of politics, economics, culture, and other related fields, and includes 66 member countries. Apart from Cyprus, the Czech Republic, Greece, Hungary, Israel, and Singapore, the remaining 60 countries are all developing countries: (1) East Asia: China, Mongolia; (2) The association of southeast Asian nations (ASEAN): Singapore, Malaysia, Indonesia, Myanmar, Thailand, Laos, Cambodia, Vietnam, Brunei, and the Philippines; (3) West Asia: Iran, Iraq, Turkey, Syria, Jordan, Lebanon, Israel, Palestine, Saudi Arabia, Yemen, Oman, United Arab Emirates, Qatar, Kuwait, Bahrain, Greece, Cyprus, and Egypt's Sinai Peninsula; (4) South Asia: India, Pakistan, Bangladesh, Afghanistan, Sri Lanka, the Maldives, Nepal, and Bhutan; (5) Central Asia: Kazakhstan, Uzbekistan, Turkmenistan, Tajikistan, and Kyrgyzstan; (6) The Commonwealth of Independent States (CIS): Russia, Ukraine, Belarus, Georgia, Azerbaijan, Armenia, and the Republic of Moldova; (7) Central and Eastern Europe (CEE): Poland, Lithuania, Estonia, Latvia, Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Bosnia and Herzegovina, Montenegro, Serbia, Albania, Romania, Bulgaria, and Macedonia. The division of the \u201cB&R\u201d countries is based on the World Bank's division of global regions and international political and economic organizations. There is a lack of cancer-related data in Palestine and Yemen in this database. Therefore, we collected and analyzed cancer data in the other 64 member states.In this study, we used incidence, mortality, and age-standardized rates (ASRs) to analyze and compare cancer incidence and death in \"B&R\" countries. Incidence, generated by population-based cancer registries (PBCRs), is the number of new cases occurring in a specified period and geographic region, and conveyed either as an absolute number of cases per annum or as a rate per 100,000 people per year. Mortality, similarly, is used to measure the number of deaths per unit of time in a population of a given size. It is usually expressed in units per 100,000 people per year. ASRs per 100,000 people-years are corrected by the direct method and the world standard population to allow for differences in the age structure of a population. The methods used to estimate the global incidence and mortality in 2020 can be found in other literature , 9. We cWe conducted a descriptive analysis and comparison of the incidence and deaths due to cancers in the \u201cB&R\u201d countries, as well as a visual presentation. Microsoft Excel 2019 was used for data visualization.A total of 26 cancers were included in the study. Breast, lung, colorectum, prostate, stomach, liver, cervix uteri, esophagus, thyroid, and bladder cancer ranked amongst the top 10 new cancer in 2020, and lung, colorectum, liver, stomach, breast, oesophagus, pancreas, prostate, cervix uteri, and leukaemia cancer ranked among the top 10 cancer in terms of deaths, with a total of 12,176,526 new cases and 7,054,094 deaths worldwide, respectively Table .Table 1NTable Among the top 10 cancers in East Asian countries, the total incidence and mortality of cancer in Mongolia were ASR, 158.0 per 100,000 and ASR, 128.8 per 100,000, respectively, and both were larger in females than in males. Liver cancer had the highest cancer incidence and mortality. The total cancer incidence and mortality in China were 146.3 per 100,000 and 84.4 per 100,000, respectively, and lung cancer and breast cancer had the highest cancer incidence and mortality, respectively and Vietnam had the highest cancer mortality . The countries with the highest overall cancer incidence and mortality among males were Singapore and Laos , while for females, the country was Brunei, with an overall cancer incidence and mortality of ASR, 137.4 per 100,000 and ASR, 52.9 per 100,000, respectively. Cancers of the colorectum, lung, prostate, and liver in men, and cancers of the breast, lung, colorectum, and cervix uteri in female, continue to be the most common fatal cancers and Turkey , with lung, prostate, bladder, and colorectal cancer being the main causes. Israel, Greece, and Cyprus had the highest cancer incidence rates of the breast, thyroid, corpus uteri, and colorectum in females. The top three countries with the highest cancer mortality were Cyprus, Egypt, and Iraq, where principal deaths of cancer were cancers of the breast, lung, colorectum, ovary, and cervix uteri; leukemia, brain, and central nervous system were all in the top five cancer death types in Iraq. See supplementary Fig. SLarge distribution differences existed in the incidence and mortality of cancers in South Asian member countries, with the total number of newly diagnosed cancer cases in Bhutan being much higher than that in other countries . Bangladesh had some of the highest cancer incidence rates in males , such as lung, prostate, and colorectal cancers. There was a high incidence of breast cancer, colorectal cancer, non-Hodgkin lymphoma, and esophageal cancers in females in Afghanistan and the Maldives . On the contrary, deaths were more evenly distributed across countries, with the most deaths being from lung cancer and digestive system cancer in males and breast cancer and lung cancer in females. See supplementary Fig. SLung, prostate, colorectal, and stomach cancers in males in Kazakhstan and Uzbekistan had a high incidence among the Central Asian countries, while a small difference in the incidence and mortality of cancers was observed in females; cancers of the breast, cervix uteri, colorectum, corpus uteri, and stomach were the main ones , ranking the first among the types of cancer worldwide . The risIn addition, cervical cancer carries the highest burden in less developed countries and regions in the \u201cB&R\u201d countries , and neaInfectious agents are the key cause of cancer, particularly in low- and middle-income countries. It was estimated that in 2018, about one-eighth of the 18 million new cancer cases in the world were caused by infection . HepatitUltraviolet radiation directly or indirectly induces DNA damage, leads to mutations, triggers inflammation and immunosuppression, and finally leads to tumor growth. Photocarcinogenesis is a complex, multi-step pathway, which is triggered by the formation of dipyrimidine photoproducts and leads to the formation of mutations . Sunburn and inflammation caused by persistent DNA lesions (including dipyrimidine photoproducts and oxidative DNA lesions) play a role in promoting the process of photocarcinogenesis . The dipIn the wake of the COVID-19 pandemic, awareness of global public health has become clearer, and policy has played a crucial role in promoting global public health. By studying and comparing the incidence, mortality and risk factors of cancer in the \u201cB&R\u201d countries, this study identified different cancer challenges faced by different countries, proposed cancer prevention and control measures applicable to each country, and provided suggestions for health cooperation programs in \u201cB&R\u201d countries. However, the data sources involved in this study are extensive, and the data quality will be uneven. Readers are suggested to quote and extrapolate after reading the analysis methods and data sources of this study in detail.In summary, the challenges posed by cancer are consistent in the \u201cB&R\u201d member countries. Lung cancer, breast cancer, gastrointestinal cancer, prostate cancer, cervical cancer, thyroid cancer, and uterine cancer were found to be the biggest cancer burdens in the \u201cB&R\u201d countries, and tobacco products, infectious factors, and ultraviolet rays were the main risk factors. Moreover, the corresponding cancer prevention and control policies need to be improved. Therefore, in the context of the health \"One Belt One Road\" initiative, the collaboration between multiple stakeholders and the sharing of resources will play a positive role in jointly coping with the risks and challenges brought by cancer and promoting the positive development of the health and medical undertaking of all member states and the world at large.All methods were carried out in accordance with relevant guidelines and regulations.Additional File 1. Supplementary file 1 Comparison of estimated 2020 ASR (world) among East Asia countries, all ages.Additional File 2. Supplementary file 2\u00a0Comparison of estimated 2020 ASR (world) among ASEAN countries, all ages.Additional File 3. Supplementary file 3 Comparison of estimated 2020 ASR (world) among West Asia countries, all ages.Additional File 4. Supplementary file 4 Comparison of estimated 2020 ASR (world) among South Asia countries, all ages.Additional File 5. Supplementary file 5 Comparison of estimated 2020 ASR (world) among Central Asia countries, all ages.Additional File 6. Supplementary file 6 Comparison of estimated 2020 ASR (world) among CIS countries, all ages.Additional File 7. Supplementary file 7\u00a0Comparison of estimated 2020 ASR (world) among Central and eastern Europe countries, all ages."} +{"text": "Introduction: Neuromuscular diseases comprise a heterogeneous group of genetic syndromes that lead to progressive muscle weakness, resulting in functional limitation. There is a gap in the literature regarding the communication of the diagnosis of such diseases, compromising the autonomy of patients and families, besides causing stress on the assistant physician. Objectives: Developing a guide to reduce communication barriers in the diagnosis of neuromuscular diseases. Methodology: Systematic review, after searching the descriptors (\u201cMuscular Diseases\u201d OR \u201cNeuromuscular Diseases\u201d) AND (\u201cTruth Disclosure\u201d OR \u201cBad news communication\u201d OR \u201cBreaking bad News\u201d) in the Pubmed, Bireme, and Scopus websites, and these results were analyzed through narrative textual synthesis. Results: 16 articles were submitted to the final analysis, giving rise to seven steps to support the communication process. These are Empathy, Message, Prognosis, Reception, Time, Individualization, and Autonomy. Discussion and conclusion: The empathic transmission of the message and the prognosis must accommodate the feelings of the interlocutors with different information needs. In this way, communication planning optimizes the time and individualizes each context, respecting the autonomy of those involved. EMPATIA reflects the bioethical and interdisciplinary analysis of the literature and comes to fill the gap related to the communication of bad news in neuromuscular diseases. Neuromuscular diseases comprise a heterogeneous group of genetic syndromes, with variable phenotypes and genotypes that affect the peripheral nervous system. These are rare diseases, which, in general, present progressive functional limitation secondary to muscle weakness, and may lead to the inability to sit, walk, perform manual activities, speak, swallow, and breathe, besides systemic complications secondary to possible damage to the heart muscle, bronchoaspiration, and respiratory infection, for example, besides musculoskeletal deformities, and death ,2,3.The care of patients with disabilities must be based on the ethical principles of beneficence, non-maleficence, autonomy, and justice, from the moment of communicating the diagnosis to end-of-life decision-making ,5. ThereImproving communication skills strengthens the physician\u2013patient/family bond, motivation and adherence to treatment, the feeling of security and hope, in addition to favoring shared decision-making, avoiding inappropriate expectations ,13,14,15Given the above, the existence of a guide to assist in the communication of the diagnosis of neuromuscular diseases is essential to reduce stress and communication barriers between students, physicians in training, and experts, favoring the ethics of individual/family-centered care.A systematic review was performed by searching for articles on the Pubmed, Bireme, and Scopus websites until May 2022. The descriptors used in Pubmed were ((Muscular Disorders) OR (Neuromuscular Disease)) AND ((Bad news communication) OR (Truth Disclosure) OR (Breaking bad news)), in Bireme and Scopus were (\u201cMuscular Diseases\u201d OR \u201cNeuromuscular Diseases\u201d) AND (\u201cTruth Disclosure\u201d OR \u201cBad news communication\u201d OR \u201cBreaking bad News\u201d). There was no restriction regarding the year of publication, and the filters used were studies in humans and English. The flowchart displaying the article selection is shown in Initially, a pre-selection of articles was conducted by the first author, followed by a final selection after analysis and discussion with the other authors, considering the interdisciplinarity inherent to the theme. After the stages of initial selection and final approval, the analysis of the articles began, independently reviewed, avoiding any ambiguity. Articles were not excluded based on the quality of the research presented, because of the small number of studies selected, and there was no superiority or need to exclude the experiences described.The articles were carefully analyzed and individually interpreted through the following questions: 1. What factors have positively impacted the communication of the diagnosis of a neuromuscular disease? 2. Which communication barriers were described during the communication of this diagnosis? Except for some cases of basic numerical analysis of percentages, the data used for our research questions were qualitatively analyzed, after a synthesis of correlated results, and grouped through narrative textual synthesis, constituting a communication guide . ResultsThis guide was prepared after a neurologist with expertise in neuromuscular diseases, a specialist in medical law and bioethics, and a researcher specialized in palliative care and bioethics analyzed the results. Suggestions and critical remarks were sent by email to the first author, who conducted the final review and evaluation.The following communication protocols for breaking bad news were used as a basis: SPIKES, the Six-Step Protocol for Delivering Bad News , EFNS guSixteen articles were included for the final analysis after the selection of the systematic review. Five (31.2%) of them describe the perspective of people diagnosed with Amyotrophic Lateral Sclerosis (ALS), two (12.5%) report the experiences of family caregivers of people diagnosed with ALS, two (12.5%) of family caregivers of people with Duchenne muscular dystrophy (DMD), one (6.25%) of family caregivers of people with spinal muscular atrophy (SMA), three (18.75%) are mixed studies involving affected people and their caregivers , two (12.5%) involve neurologists, and one (6.25%) resident physicians. One article obtained during the search in the references approaches the perspective of communication of the diagnosis between family members and people with genetic diseases, linked to the X chromosome, which, despite not directly addressing neuromuscular diseases, was selected for the final analysis because of the similarity related to rarity, genetic origin, functional impairment, absence of curative treatment, and need for continued rehabilitation . The artThe selected studies describe experiences from the United States of America, Canada, Europe, Australia, and Brazil . SamplesThe analysis of the results gave rise to the EMPATIA Communication Guide, subdivided into seven steps to support the transmission of the diagnosis of neuromuscular diseases, they are Empathy, Message, Prognosis, Acknowledgment, Time, Individualization, and Autonomy .Empathy is the essence of this communication guide. Despite being considered a basic skill , severalThere must be medical preparation before the consultation so that breaking bad news does not result in a communication barrier ,25,29 duProfessionals must keep in mind that empathically communicating the truth does not harm the quality of life of their patients, and may also improve their vitality ,33, reduThe diagnosis must be informed in person, whenever possible ,16,17,20Attention must be given to the feeling of privacy regarding the physical environment, the number of professionals and students during the breaking of bad news, and the opportunity for patients to get dressed, if they have been recently examined ,16,20,31As tables or desks may be perceived as a communication obstacle, professionals must sit close to the patients, preferably side by side and at the same level, and look at them with care, indicating interest and allowing active listening ,16,20. TThe diagnosis must not be omitted. The \u201cconspiracy of silence\u201d or \u201cpious lie\u201d is a way of \u201csparing\u201d the patient; or the distortion of information by, for example, using generalized terms such as \u201cdiseases of the nervous system\u201d and \u201cdamage of motor nerves\u201d instead of the actual name of the disease ,16,29,35The message must be communicated clearly and up to date, with accessible vocabulary, an appropriate tone of voice, uses of examples, metaphors, but also simple drawings or images. Sentimentality, ambiguity, understatement, medical jargon, and impersonal expressions must be avoided ,26,27,28Physicians must also listen to the patients and make sure that the message transmitted was understood and, if there are any doubts, show patience, interest, and availability for further clarification ,25,28,30Written referrals to rehabilitation services and other medical specialties, such as geneticists for genetic counseling, pulmonologists, orthopedists, among others, are recommended. Interdisciplinarity is essential for having a positive impact on the communication process, therapeutic planning, and the establishment of clinical and rehabilitation goals, improving functional independence, preventing complications, in addition to functioning as a support network, avoiding inappropriate conduct, financial expenses, and waste of time ,29,30,31Delivering a summary or providing materials related to the subject addressed in the consultation is essential; professionals must also provide information on support groups, associations, labor rights, assistance benefits for people with disabilities, and reliable research sources ,27,29,30Physicians must maintain proper communication at each stage of evolution. Every conversation has to involve individualized support in the short, medium, and long term ; therefoBreaking news for patients in childhood age:The needs of the doctor/child/legal guardian trinomial must be individualized, with guidance to parents and family members who must have their doubts clarified to feel prepared to talk about the diagnosis in the different stages of maturity of their children ,22,23,31\u201cKeeping the child away from information\u201d should be avoided as, for example, a \u201cfamily secret\u201d, since this attitude generates tension in the family environment, in addition to upset, frustrated, and anxious children and adolescents, with a continuous feeling of mistrust. The principle of truth, besides being an ethical stance, positively impacts the communication of the diagnosis . DiscussPhysicians must listen to children, encourage them to ask questions, and share their feelings . Open, hIn this context, attention is needed towards \u201cthose forgotten to be informed\u201d, such as siblings of patients who, anguished, isolated, and silent, endure a family history of genetic and neurodegenerative disease , carryinAnother relevant recommendation is for professionals not to anticipate prognosis or determine a lifespan. Prognostic information should be individualized and realistic, understanding information needs and clarity ,9,16,30,Honesty about progression and acknowledging the severity of the disease, maintaining \u201crealistic hope\u201d through communication about neuroprotective and disePhysicians must teach, guide, and clarify doubts continuously at each stage of evolution, so that patients feel prepared in case of complications and safe to make therapeutic and palliative decisions, reducing the feeling of fear and anxiety ,25,28,36Being sensitive to spiritual needs demonstrating compassion are also essential traits for health professionals. Even in the face of a bad prognosis, these behaviors may be sources of comfort, peace, hope, and belonging. When the medical team does not feel able to talk about spirituality or has divergent thoughts from the patient, spiritual counseling may help to reflect on faith, beliefs, and values ,40. StudAnother essential indispensable step is acknowledging fear, insecurity, pain, anger, denial, anxiety, outburst, revolt, sadness, or silence . After cProfessionals must take care of their emotional health and acknowledge it. Their emotional reaction is an important communication barrier ,25,28; tPlanning the step by step of this communication guide to adjust the time and reduce situations that show that the time is limited, such as interruptions and staring at the clock, is essential ,29. The Physicians must also individualize the process, adapting this guide to the context related to the emotional, social, cultural, intellectual, financial, and religious issues of those involved and the information needs, centered on the patient and their family caregivers ,25,28. EJudgment must be avoided and be replaced by guidance and support throughout the course of the disease ,22. Not Adapting the service environment is also recommended, organizing tables and chairs, accessibility, noise reduction, and privacy, in addition to the training and guidance of a care team that involves all the staff, from the doorman to professionals who perform general services and secretaries, to facilitate accessibility and have empathic postures and conducts that value equity. The involvement of other health professionals in the integrated and continuous treatment is essential, besides the administration of the appointment schedule according to Step 2.8, and 2.9.The desired consequence of the EMPATIA guide is respect for the autonomy of those involved. Efficient communication favors consent and conscious and voluntary decision-making by patients or their legal guardians . ProfessThis systematic review has demonstrated that empathic communication of the diagnosis and prognosis of a neuromuscular disease requires availability and management of time for individualized technical clarification according to the particularities of the patients and their caregivers. After the necessary information is given, there must be acknowledgment and guidance on which paths to follow in order to respect the autonomy of those involved.In this way, the EMPATIA guide reflects the bioethical analysis of the literature related to breaking bad news about neuromuscular diseases, based on internationally supported protocols and a transparent and objective systematic review, discussed in an interdisciplinary manner. This guide fills the gap related to the communication of the diagnosis and the need for technical training of neurologists ,26,27,29The authors intend to analyze the impact of EMPATIA on several aspects, such as the communication of the diagnosis of neuromuscular diseases, the physician\u2013patient relationship, the stress related to the doctor during this moment ,12,26,27The limitations of this guide comprise the lack of research related to the communication process of the diagnosis for most neuromuscular diseases and the absence of this type of investigation in several continents, which may require cross-cultural adaptations or specific adjustments regarding some neuromuscular diseases."} +{"text": "Artocarpus lakoocha is a synonym for Artocarpus lacucha and is a plant that can be found in Indonesia. This medicinal plant has been used to treat many diseases. (1) Objective: This article discusses the scientific investigations carried out on A. lacucha, namely the plant\u2019s chemical content, pharmacological activity, and active compounds. (2) Methods: The design of this study was based on an article that was a review of previous research. A search for relevant publications over the past ten years (2012\u20132022) using data from Pubmed, Proquest, Ebsco, ScienceDirect, and Google Scholar resulted in the discovery of 369 articles. (3) Results: Fifty relevant articles investigate A. lacucha\u2019s substances and their applications in the health field. The presence of secondary metabolites and bioactive compounds has been reported, which is evidence that A. lacucha possesses antidiarrheal, immunostimulant, anticholesterol, and hepatoprotective agents. (4) Conclusions: Mobe (A. lacucha) is a plant native to North Sumatra, Indonesia. This plant is efficacious as an antioxidant, antibacterial, antidiarrheal, anti-inflammatory, analgesic, antinociceptive, schistosomicidal, hepatoprotective, neuroprotective, cytotoxic, antiglycation, and anticholesterol, and can also be used for anti-aging and wound healing. In addition to its various benefits, it turns out that this plant also has many active compounds that are useful to the health sector, especially the pharmaceutical field.Studies have shown that approximately two-thirds of the plant species in the world have some medicinal value. In Indonesia, where there are many different ethnic groups, plants are used as medicines in increasingly different ways . The numAntidotes made from plants have been used for thousands of years. Our ancestors used them and passed them down from generation to generation until they finally made it into the pharmaceutical world and were recognized by science . Many peA. lacucha is a species of Artocarpus from the Moraceae family , antibacterial, antimalarial, antituberculosis, antiplasmodial, antiatherosclerotic, antifungal, antidiarrheal, antidiabetic, wound healing, anti-inflammatory, and anticancer and also contain active compounds such as artocarpin, oxyresveratrol, phenols, and flavonoids . Ad. AdA. laA. lacucha plants contain several active compounds, which have been discussed in this article. One of them is oxyresveratrol, which has anti-aging activity associated with its high phenol content, free radical scavenging activity, and antiglycation activity [activity ). Oxyresactivity ,78,79.A. lacucha fruit has antibacterial, antihelmintic, and cholesterol-lowering properties agent in Alzheimer\u2019s disease [Based on the results of the literature study, it can be stated that the operties . People nd drugs ,13. The nd drugs . They alnd drugs . Other i disease ,83,84."} +{"text": "In the published article, the author names were incorrectly written as Na Z, Kevin F, Yoshiki M, Corentin S, Malgorzata K, Robert N and Vitalie F. The correct author names are Zhou N, Forton K, Motoji Y, Schoubeau C, Klass M, Naeije R and Faoro V.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Antibodies are key reagents in diagnostics, therapeutics, and experimental biology, capable of detecting numerous targets. The immunization of animals with antigens mixed with an adjuvant and the induction of antibodies is a well-established process. This procedure for the generation of monoclonal antibodies was originally described by K\u00f6hler and Milstein, and is well-known and has been thoroughly tested ,2,3,4,5.The choice of suitable peptides is crucial for the generation of a good peptide antibody. The peptides used are typically 10\u201320 amino acids long and can be designed to represent many different targets, e.g., post-translational modifications, terminal ends, areas of high conservation, turns, loops, \u03b1-helices, etc. ,5. BasedIn addition to peptide antibodies obtained by the immunization of animals, they can be produced using mammalian expression systems, which facilitate native antibody folding and post-translational modifications . This ap2LC2) linked via disulfide bonds, although some antibodies are occasionally prone to dimerization, or even oligomerization, as recently described by Mieczkowski et al. [Antibodies are typically expressed in a basic format with two HCs and two LCs antibodies should be characterized in terms of reactivity, specificity, and cross-reactivity, e.g., by titration assays and competition studies, where the relevant target is used as an inhibitor ,3,5. MorPeptide antibodies are used for research and diagnostics in many different immunoassays, e.g., immunohistochemistry, immunocytochemistry, immunoblotting, immunoprecipitation, and sandwich assays ,11,15,24The seven articles featured in this Special Issue, addressing the design, production, characterization, and use of (peptide) antibodies, are of considerable interest to scientists investigating approaches related to this topic."} +{"text": "Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism.Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science\u2122 database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words.The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research.Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers. AlthougRheumatism encompasses a wide range of diseases . AccordiSequencing technology, that is, the technology that detects the sequence pattern of biomacromolecules in the central dogma of molecular biology. covers DNA sequencing to RNA sequencing to protein sequencing and provides us with insights into the relationship between genotypes and phenotypes . It laidThe progress made in sequencing technologies has been echoed in the recently improved understanding of rheumatism. The advancement and widened application of sequencing technology and bioinformatics has helped us to take a deeper look into rheumatic diseases on their molecular and cellular levels, and has become an indispensable research tool for its great contributions to the classification, pathogenesis, diagnosis, and treatment of rheumatic diseases. GWASs could be used to explore associations between genetic variants and phenotypes . The incBibliometrics takes the global document characteristics and literature landscape as its research object and utilizes methods that include statistics and mathematics to explore the quantitative relationships, changing laws, and distribution patterns of document information, thereafter the characteristics, structures, and laws of technology and science are analyzed. , which c22.1The Web of Science\u2122 , the most trusted global database, and the strongest search engine, was used for publication retrieval on 25 April 2022. The retrieval strategy was as follows: (((TS=rheumatology) OR (TS=rheumatic disease) OR (TS=rheumatism)) AND ((TI=transcriptomic) OR (TI=proteome) OR (TI=proteomics) OR (TI=metabolomics) OR (TI=bioinformatics) OR (TI=metagenomics) OR (TI=metatranscriptomics) OR (TI=omics) OR (TI=microarray) OR (TI=sequence) OR (TI=RNA-seq) OR (TI=sequencing) OR (TI=ATAC-seq) OR (TI=single cell sequencing) OR (TI=single cell sequence) OR (TI=single cell RNA sequencing) OR (TI=single cell RNA sequence) OR (TI=expression profile) OR (TI=bioinformatic*) OR (TI=high throughput))). We retrieved a total of 1,374 articles published from 1 January 2000 to 25 April 2022 in the Web of Science Core Collection. Reviews and monographs were excluded as publication types, and articles, meeting abstracts, proceedings papers, editorial material, letters, and corrections were retained (2.2www.r-project.org) for quantitative research in scientometrics. Bibliometrix can support the workflow for bibliometric analysis and can be easily upgraded and integrated with other R packages , an open-source tool developed by Massimo Aria and Corrado Cuccurullo using statistical computing and R language . Other tanalysis . VOSviewanalysis , was als33.1Since the year 2000, publications in rheumatism sequencing have shown an overall tendency of growth. From 2000 to 2004, few articles were published in this area. In 2005, the number of publications increased in line with the development of proteomics and maturation of microarrays. After 2009, with the emergence of single-cell sequencing, publication numbers rapidly increased, with more effort dedicated to the field using this technology. The data retrieval date (April 25) may account for the steep decline in 2022 Figure\u00a013.2A total of 1,374 articles were retrieved, from 62 countries, led by the USA and China, which accounted for 334 publications and 300 publications, respectively, creating a huge production gap between these two countries and the rest of the world. Ranked by accumulated publication frequency, the USA came first, with 1,592 publications, and China second, with 982 publications , Brigham and Women\u2019s Hospital (n\u00a0=\u00a041), the Karolinska Institute (n\u00a0=\u00a034), Leiden University (n\u00a0=\u00a034), and the University of California, San Diego (n\u00a0=\u00a034), four of which are in the USA. Shanxi Medical University, the affiliation of the most prolific author, Li, and the University of Minnesota, the affiliation of the third most prolific author, Baechler, also made the top 20. These results are in line with the accumulated production figures for countries noted above, indicating that the USA is in the vanguard of the field.The source of authors\u2019 inspiration, and the incubator for their discoveries, is their institution. Thus, it is of great importance to identify the prolific institutions. 3.3Annals of the Rheumatic Diseases, and Arthritis & Rheumatism were the top three, all with publications numbers surpassing 140, accounting for the majority of the relevant articles , Annals of the Rheumatic Diseases (H\u00a0=\u00a017), and Arthritis & Rheumatology (H\u00a0=\u00a016), making them valuable sources for research related to rheumatism and sequencing are words or phrases that are calculated by special algorithms that do not appear in the title of the article but appear in the titles of the article\u2019s references. Article keywords, in contrast, are supplied by the article authors themselves. The KeyWords Plus analysis had achieved the important milestone of completion of a working draft sequence, ushered in the post-genomics era, which placed more stress on the study of functional genomics, specifically the dynamic genome, and its products such as RNA, proteins, and metabolites . In lineIn this bibliometric analysis, we examined 1,374 articles published from 2000 to 2022 (April 25) on sequencing technology and rheumatism.The number of annual publications, to a certain extent, can reflect the level of researchers\u2019 interest in the field. The number of articles on rheumatism and sequencing started to increase significantly after 2000 and has continued to exhibit an overall increase, despite a few ups and downs. In the year 2005, the number of publications saw its first peak, with most publications focusing on proteomics and gene expression profiling. The same theme lasted for years, until the technique of single-cell RNA sequencingbecame mature and was widely deployed, as a result of which it became the most popular research topic in rheumatism and sequencing. Sequencing in rheumatism regained its popularity in 2009, and the number of articles published increased to nearly 100 per year. In 2017, the publication number received another boost, and in 2021 reaching a record high of 152 publications.Among the 62 countries that dedicated efforts to this field, the USA ranked first, in terms of both the total number of documents and total number of MCPs, and was the home to a large proportion of most relevant affiliations, such as Stanford University, the University of California, San Francisco, and so on. China came in second in total publication numbers, but had the highest number of SCPs. Countries also worked together to conquer obstacles, with the USA having the strongest cooperative bonds with China, European countries, and Korea. Switzerland had the highest MCP ratio, indicating that most of its publications resulted from collaboration with other countries. In terms of the most relevant authors, Li from Shanxi Medical University and Liu from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine were at the top, with 16 and 15 related articles published in total, respectively, and they are still very active today. Baechler of the University of Minnesota and Gregerson of the Feinstein Institutes for Medical Research reached their peak publishing activity in 2005, and their output has since gradually declined. Several connections can be found between the most relevant authors and affiliations. For instance, Shanxi Medical University, which ranked 12th on the most relevant affiliations, is the institution where Li, the most prolific author, works. This indicates that the most relevant authors also played prominent roles in the establishment of great teams and research environments in this field.Arthritis & Rheumatology, Annals of the Rheumatic Diseases, and Arthritis and Rheumatism were the three most relevant sources, among which the first two presented an increase in 2013. Although PLOS ONE had only an impact factor of 3.752 in 2022, it published 36 relevant articles and had an h-index of 19, so its influence on the subject should not be ignored.Streptococcus pyogenes\u201d and transcription factor 7 (TCF7), novel SLE susceptibility genes, were uncovered by GWASs and expression quantitative trait loci (eQTL) analysis and diseases, to estimate the possible risks or susceptibility. For instance, using large-scale GWASs, researchers identified the significant genetic variants connected with rheumatoid arthritis susceptibility . Nicotinanalysis . All wor4.2.2Cluster 2 was colored in red, and consisted of the terms \u201cexpression\u201d, \u201cidentification\u201d, \u201cgene\u201d, \u201cprotein\u201d, \u201ccartilage\u201d, and \u201carticular-cartilage\u201d, concentrating on the molecular basis of rheumatism. More and more relevant molecules, whether genes or proteins, have been found, using sequencing technologies such as microarray, to play a pivotal role in rheumatic disorders. Take SLE as an example: the etiology of SLE is multifactorial, involving genes, epigenetic factors, and autoantibodies . Utilizi4.2.3COL6A3) and actin gamma 1 (ACTG1)] as key components of OA , identified the focal adhesions pathway and two marker genes [i.e., collagen type VI alpha 3 chain and refined our classification standards for SLE . Ambigui4.2.5SAA4), gelsolin (GSN), and vitamin D-binding protein (VDPR) as RA biomarkers, which has value for not only the diagnosis but also the prevention and treatment of rheumatic diseases classification criteria for RA\u2019sdiseases . He ZR ediseases . Similardiseases . The disAlthough keywords were separated into five clusters, cross-links between clusters still existed. Exploring the genetic expression pattern could also contribute to an understanding of an individual\u2019s susceptibility to rheumatic diseases, as well as their disease classification status. Discovering novel biomarkers could also lead to the further explication of the pathological or physiological progress involved in rheumatism. Thus, it is of great importance to bear in mind the close relationship between these key themes. In addition, of the various diseases that rheumatism covers, it is apparent that RA, SLE, and OA are the hottest spots for research, with solid foundations and great clinical significance. All in all, sequencing technology was introduced to rheumatism studies to find solutions for unsolved problems, but it is now altering and even leading groundbreaking studies in rheumatism.Nevertheless, limitations in our study still exist. Our study included only articles published from 2000 to 2022, which might have led to the oversight of both early important studies and the latest updates.5In this bibliometric study, we reviewed the progress made in the last 22 years in sequencing and rheumatology, and identified the hotspots and frontiers for future investigation. Evidently, sequencing technology has invigorated the study of rheumatism. From the standpoint of pathogenesis, genomic sequencing has equipped us with knowledge of the pathogens involved, and identified possible genetic backgrounds and molecules involved in the pathogenesis of rheumatism. From the standpoint of clinical value, genomic sequencing has identified possible markers for diagnosis, supplemented evidence for defining stages and classifications, and spotted potential targets for therapy. Among those contributions, employing sequencing technology to study the pathogenesis and classifications of rheumatism would be a wonderful direction for future studies to take. Discovering novel biomarkers for diagnosis and uncovering genetic patterns related to disease susceptibility are also promising orientations. We hope that, with this bibliometric study, we can provide a reference for researchers to better grasp the trends and key points of the study of rheumatism.The original contributions presented in the study are included in the article/Conception/design: RH, JT, SW, YLiu, MZ, MJ, HQ, WQ, YLu, YiY, BL, YuY, PY, JH, WZ, JL, MG, YZ, XG, SX, XL, and ZH. Collection and/or assembly of data: RH, JT, SW, YLiu, MZ, MJ, HQ, WQ, YLu, YY, BL, YY, PY, JH, WZ, JL, MG, YZ, XG, SX, XL, and ZH. Data analysis and interpretation: RH, JT, SW, YLiu, MZ, MJ, HQ, WQ, YLu, YiY, BL, YuY, PY, JH, WZ, JL, MG, YZ, XG, SX, XL, and ZH. Manuscript writing: RH, JT, SW, YLiu, MZ, MJ, HQ, WQ, YLu, YiY, BL, YuY, PY, JH, WZ, JL, MG, YZ, XG, SX, XL, and ZH. Final approval of manuscript: RH, JT, SW, YLiu, MZ, MJ, HQ, WQ, YLu, YiY, BL, YuY, PY, JH, WZ, JL, MG, YZ, XG, SX, XL, and ZH. All authors contributed to the article and approved the submitted version."} +{"text": "In the published article, there was a misprint in affiliations. Instead of \u201cDepartment of Neurosurgery, Asan Medical Center, Seoul, South Korea\u201d it should be \u201cDepartment of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea\u201d. Additionally, instead of \u201cDepartment of Radiology, Asan Medical Center, Seoul, South Korea\u201d it should be \u201cDepartment of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In this article Gunter Bombaerts was incorrectly linked to 'Delft University of Technology, Jafalaan 5, 2628BX Delft, The Netherlands', due to an incomplete correction. He should have been linked to 'Eindhoven University of Technology, VITO, Eindhoven, The Netherlands', as he was in the original manuscript.The original article has been corrected."} +{"text": "In the midst of a global pandemic with a rising death toll, the children\u00b4s mental health can be easily overlooked in the country\u2019s response. But this overlook would have devastating consequences for years to come.The objective of this research is to compare children\u2019s physical and mental development before, during and after the situation of social isolation caused by the pandemic of COVID-19.The parents/guardians of 100 children aged between 0 and 5 years and 11 months old were asked to answer questions based on the ASQ-3 (Ages and Stages Questionnaire III), containing questions related to Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social and ASQ- SE addressing issues of self-regulation, compliance, social-communication, adaptive functioning, autonomy, and affect. In addition, behavioral issues related to children\u2019s mental health will be included, such as: aggressiveness, insomnia, lack of appetite, apathy, sadness, tiredness, lack of interest, hyperactivity, manias, tantrum, morning among others. Child development data will be collected before and during quarantine / isolation and later, in a second stage, after the end of social isolation.The data will be analyzed in order to characterize child behavior before, during and after the period of social isolation, correlating the different areas of child development, especially mental health.As argued, socially isolated children are at increased risk of health problems in adulthood. Furthermore, studies on social isolation have demonstrated that a lack of social relationships negatively impacts the development of the brain\u2019s structure.No significant relationships."} +{"text": "Video and other technologies are reshaping the delivery of health care, yet barriers related to workflow and possible provider fatigue suggest that a thorough evaluation is needed for quality and process improvement.This scoping review explored the relationship among technology, fatigue, and health care to improve the conditions for providers.A 6-stage scoping review of literature (from 10 databases) published from 2000 to 2020 that focused on technology, health care, and fatigue was conducted. Technologies included synchronous video, telephone, informatics systems, asynchronous wearable sensors, and mobile health devices for health care in 4 concept areas related to provider experience: behavioral, cognitive, emotional, and physical impact; workplace at the individual, clinic, hospital, and system or organizational levels; well-being, burnout, and stress; and perceptions regarding technology. Qualitative content, discourse, and framework analyses were used to thematically analyze data for developing a spectrum of health to risk of fatigue to manifestations of burnout.Of the 4221 potential literature references, 202 (4.79%) were duplicates, and our review of the titles and abstracts of 4019 (95.21%) found that 3837 (90.9%) were irrelevant. A full-text review of 182 studies revealed that 12 (6.6%) studies met all the criteria related to technology, health care, and fatigue, and these studied the behavioral, emotional, cognitive, and physical impact of workflow at the individual, hospital, and system or organizational levels. Video and electronic health record use has been associated with physical eye fatigue; neck pain; stress; tiredness; and behavioral impacts related to additional effort owing to barriers, trouble with engagement, emotional wear and tear and exhaustion, cognitive inattention, effort, expecting problems, multitasking and workload, and emotional experiences . An additional 14 studies that evaluated behavioral, emotional, and cognitive impacts without focusing on fatigue found high user ratings on data quality, accuracy, and processing but low satisfaction with clerical tasks, the effort required in work, and interruptions costing time, resulting in more errors, stress, and frustration. Our qualitative analysis suggests a spectrum from health to risk and provides an outline of organizational approaches to human factors and technology in health care. Business, occupational health, human factors, and well-being literature have not studied technology fatigue and burnout; however, their findings help contextualize technology-based fatigue to suggest guidelines. Few studies were found to contextually evaluate differences according to health professions and practice contexts.Health care systems need to evaluate the impact of technology in accordance with the Quadruple Aim to support providers\u2019 well-being and prevent workload burden, fatigue, and burnout. Implementation and effectiveness approaches and a multilevel approach with objective measures for clinical, human factors, training, professional development, and administrative workflow are suggested. This requires institutional strategies and competencies to integrate health care quality, technology and well-being outcomes. Earltechnology fatigue [Findings from VDT studies of occupational hygiene and ophthalmologic dimensions appear to be quite pertinent to video, EHR, and psychosocial work commonly associated with fatigue ,10,76. J fatigue , and com fatigue ,78.Displays and workflow interventions have been successful in many respects. A 15-minute work period with microbreaks and physThere are overlaps and differences between burnout and prolonged fatigue . Fatigueindividual level may involve the following: (1) changing work patterns, (2) developing coping skills, (3) obtaining social support, (4) using relaxation strategies, (5) promoting good health and fitness, and (6) developing a better self-understanding. At the workplace or organizational level, this may mean the following: (1) redesigning job tasks, (2) improving recognition of notable work by both teams and individuals, and (3) developing more fair and equitable policies.Conceptualization of fatigue and burnout may also be organized according to engagement and job stress ,25,83. EA shift to a culture of well-being with technology use requires the evaluation, implementation, and monitoring of individual, workplace, workflow, and institutional strategies and IT, use of lean methods and emphasis on interprofessional education efforts with technology team-based care from the Institute of Healthcare Improvement and Agency for Healthcare Research and Quality . More spHealth care provider well-being and health appear to be related to the technological integration of video, EHR, and mobile health over time . This fiStudies related to the implementation and evaluation of technology are increasingly sophisticated and provide a starting place despite varying widely in duration, approaches, methods, and quality of measures. The 12 studies that met all the inclusion criteria for technology, health care, and fatigue studied the behavioral, emotional, cognitive, and physical impact of workflow at individual, hospital, and system or organizational levels 8,13,1414,45-53.burnout is undergoing change, with a shift toward the recognition of burnout as an occupational phenomenon rather than solely as an individual medical disease per the World Health Organization [Beneficial changes in workplace culture, focus on well-being, and prevention of burnout from other fields are beginning to be used in health care ,49,86, bnization . Thus, dwrap-around support for providers, not just patients, may be needed, as suggested by the Quadruple Aim. In the business culture of successful companies, such as Cirque du Soleil, L\u2019Oreal Paris, and Nintendo, the tetrad foci of research, production, marketing, and finance have been expanded to a pentad by integrating technology rather than appending it [To begin to address challenges in health care related to fatigue and burnout, including those associated with technology, a substantial collaborative effort is needed from health system leadership, organizational researchers, IT and IS specialists, and potentially the government ,3,28,29,nding it ,38,88. Anding it based onnding it .therapeutic, enjoyable and easy to provide, and promotes their well-being and performance as individuals, team members, and leaders. In time, continuous data collection and analytics could support clinical decision-making for patient quality, workforce satisfaction, and system outcomes, creating an organizational culture of well-being, compassion in care, and prevention of fatigue and burnout in all employees, including providers [A structural and functional redesign of systems would emphasize evaluation, effectiveness, implementation, and application of process improvement ,60,85,89roviders ,3,90. Huroviders ,85.workplace at the individual, clinic, hospital, and system or organizational levels may need better definitions. Sixth, the review does not cover all potentially relevant well-being, burnout, and stress dimensions of the workplace, nor does it cover research on the physical environment, occupational health, or mobile, virtual or telework workflows. Seventh, broader input for consensus across organizations could have been helpful, and a qualitative, small group interview approach with experts using a semistructured guide could have discovered more information.This scoping review has some limitations. First, there were fewer findings than we expected using our inclusion and exclusion criteria, despite a broad scope, to find the relationships between health care, fatigue, and synchronous and asynchronous technologies. Second, only 1 author reviewed the titles and abstracts. Third, the entire search was described but not saved and consolidated as an appendix for reviewers; reresearch findings of the 2 main databases were included as an appendix for reviewers. Although the terms, databases, and dates are a guide to other researchers, this omission does not enable others to simulate the approach. Fourth, given the small sample sizes, heterogeneous methods, and variable study duration, the team was unable to apply a systematic quality evaluation system or draw conclusions using a quantitative meta-analysis. Cross-sectional studies of associations with multiple factors in applied rather than controlled settings have limitations. Fifth, the stratification of behavioral, cognitive, emotional, and physical domains of impact, although heuristically helpful, could have been operationalized more rigorously. Similarly, Health care delivery and systems are increasingly incorporating technology but need to evaluate its impact in accordance with the Quadruple Aim to support providers. Approaches with causal questions and longitudinal implementation research could benefit from a multilevel approach with objective measures for clinical and human factors, training, professional development, and administrative workflows. If done well, technology integration could further population-centered health and effectiveness of service delivery, although the redesign of financing, reimbursement, regulatory, and other changes may be necessary. Integration of health care quality outcomes with those for technology and well-being is suggested and requires institutional strategies and competencies. Otherwise, continued advances in the use of technology may inadvertently worsen provider workload burden, fatigue, and burnout."} +{"text": "Henrique Walter Pinotti was born in S\u00e3o Paulo to Italian immigrants. He began attendingthe Hospital das Cl\u00ednicas of the Medical School of the University of S\u00e3o Paulo (FMUSP)when he was admitted to the Medical School, in 1950, participating in the ClinicalGastroenterology Service as an academic trainee under the guidance of the then head,Professor Jos\u00e9 Fernandes Pontes. He went through all sectors of the specialty, havingcontact with the pathophysiological and clinical bases of gastroenterology, deciding onsurgery on the eve of his graduation, in December 1955. Then, he was selected as asecond-year resident physician of the Department of Surgery of the Hospital, a positionheld until May 1958. During those years, he also attended the Department of PathologicalAnatomy as a volunteer.He was granted his first academic title in March 1959, when he was appointed by ProfessorAl\u00edpio Corr\u00eaa Netto, upon recommendation of Professor Arrigo Raia, Teaching Assistant ofSurgical Clinics. Later, in 1960, he was appointed FMUSP Assistant.Since then, he had the opportunity to monitor the activities and absorb the teachings ofrenowned surgeons, notable school leaders, such as Benedito Montenegro, EdmundoVasconcellos, Eurico da Silva Bastos and, especially, Al\u00edpio Corr\u00eaa Netto, from whom hereceived great encouragement for his university career, as well as from his followers,Euryclides de Jesus Zerbini and Arrigo Raia, with whom he enjoyed a close and long-termrelationship.He presented his Doctoral Dissertation at FMUSP in 1964 and became an AssociateProfessor, by public official examination, in Surgical Clinic in 1967, and thedissertations of both programs were related to Megaesophagus.In 1968, a new academic order was established: the chairs were extinguished andDepartments were created. Disciplines and departments were established; the former, infact, are specific teaching programs, and the later, the bunion of related disciplines.At that moment, the Discipline of Digestive Surgery was established at FMUSP, as well asthe respective Digestive Surgery Division at the Hospital das Cl\u00ednicas, to housesurgeons specialized in this area from the former chairs.He always sought to follow the specialty in its entirety, performing activities in allareas. With the structuring of this Discipline, he assumed, from 1974 onwards, the Headof the Esophageal Surgery Service, where he promoted great development to Brazilianesophagology.In 1981, he obtained the title of Adjunct Professor of FMUSP, and in August 1982, withthe retirement of Professor Arrigo Raia, upon recommendation of the Board of theDepartment of Surgery, he held the position of Professor of the Discipline of DigestiveSurgery of FMUSP. Subsequently, on recommendation of the same Board, he was appointedTechnical Director of the Digestive Surgery Division of Hospital das Cl\u00ednicas and itsservices: surgeries of esophagus, stomach, and small intestine, liver and portalhypertension, colon, rectum, and anus. In 1984, after a memorable civil servicecompetitive examination, he was appointed Full Professor of Digestive Surgery atFMUSP.A prominent event took place in 1986, with the establishment of the Department ofGastroenterology of the FMUSP, on the initiative of Professors Agostinho Bettarello andHenrique Walter Pinotti. This event was important for the national and internationalhistory of clinical and surgical Gastroenterology and also for teaching students,residents, and graduate students, as well as for conducting scientific and care-relatedresearch with the integration of surgeons, gastroenterologists, endoscopists, andnutrologists.Tratado de Cirurgia do Aparelho Digestivo, Acesso aoEs\u00f4fago Tor\u00e1cico por Transsec\u00e7\u00e3o Mediana do Diafragma, andFilosofia da Cirurgia ,,,,,,,In his memorial, the following stand out: 590 publications in national and internationaljournals; 26 awards; 46 films or videos and countless lectures at national andinternational congresses and courses; 191 book chapters and seven books, among whichstand out Curso de Atualiza\u00e7\u00e3o de Cirurgia do Aparelho Digestivo -Gastr\u00e3o), the most important in Digestive Surgery in Brazil. He has alwaysbeen intensely dedicated to this course, especially during his tenure. It is alsonoteworthy, in 1974, the creation of the Continuing Course in Gastroenterology(Curso Continuado em Gastroenterologia), periodically administeredin 10 annual sessions, on Saturdays, for doctors from the State of S\u00e3o Paulo andBrazil.In 1973, he was founder, together with Professors Arrigo Raia, Joaquim Jos\u00e9Gama-Rodrigues, Marcel Cerqueira Cesar Machado, and Angelita Habr-Gama, of the DigestiveSurgery Update Course (Brazilian College of Digestive Surgery (CBCD), gatheringspecialists from all over Brazil. It was registered with the Brazilian MedicalAssociation, the Brazilian Federal Council of Medicine, and competent bodies, with thespecific determinations for obtaining the degree of specialist, in addition to therecognition of medical residency in the specialty by the National Medical ResidencyCommission (CNRM)In 1986, he created the Brazilian Archives of Digestive Surgery (ABCD) with severalsurgeons from Hospital das Cl\u00ednicas and Brazil, which later became the officialscientific agency of the Brazilian College of Digestive Surgery (CBCD). This spirit ofnational union concerning the specialty also enabled, in 1988, the idealization andfoundation of the He was member of several national and international Medical Societies, notably theBrazilian Medical Association, the Brazilian Federation of Gastroenterology, theBrazilian College of Surgeons, the American College of Surgeons, the InternationalSociety of Diseases of the Esophagus, and the International Association for GastricCancer. In particular, his activities at the International Society for Diseases of theEsophagus (ISDE) are noteworthy, where he was president of the 2001 World Congress, heldin S\u00e3o Paulo, Brazil.He made numerous study trips inside and outside the Country. In Brazil, he participatedin congresses, courses, and medical conferences in most states, visiting its mainmedical and university centers, where he had the opportunity to learn about the problemsrelated to regional clinical pathology, medical assistance, professional issues,scientific research, and especially medical education.Doctor Honoris Causa ofthe University of Goi\u00e1s (Brazil), University of Coimbra , and University ofMilan .He received numerous honors, including the title of He became Professor Emeritus at the Medical School of the University of S\u00e3o Paulo in2000.grupodos Zezinhos (\u201cgroup of Zezinhos\u201d), who carried out theirundergraduate research by instrumenting their surgeries and participating in clinicaldiscussions. It is also worth noting his dedication to the 71 HCFMUSP Digestive Surgeryresidents trained under his guidance and to the 26 private Service residents at HospitalNove de Julho. He actively participated in graduate studies advising 57 surgeons andseveral assistants, including the authors of this text.For those who knew and related to Prof. Pinotti, he was an authentic leader, who showedgreat dedication to undergraduate education, in particular by creating a center foreducational training in surgery for fourth-year students, the so-called We thank him on behalf of all of them, quoting his own words: \u201cThe mission for which weset ourselves has been achieved, the climax generates a state of tranquility as we haveculminated in one of the fundamental actions of the University Professor of Surgery,which is to transmit what he knows.\u201d"} +{"text": "N = 51) were charted, and a qualitative content analysis was conducted. Five themes were formed which provided insights into how both physical and social environmental qualities combined provide for maximum play value in outdoor play experiences. These multifaceted play experiences included the desire for fun, challenge, and intense play, the wish to self-direct play, and the value of playing alone as well as with known people and animals. Fundamentally, children wished for playgrounds to be children\u2019s places that were welcoming, safe, and aesthetically pleasing. The results are discussed in respect to social, physical, and atmospheric environmental affordances and the adult\u2019s role in playground provision. This scoping review represents the valuable insights of children regardless of abilities and informs about how to maximise outdoor play experiences for all children.For children, playgrounds are important environments. However, children\u2019s perspectives are often not acknowledged in playground provision, design, and evaluation. This scoping review aimed to summarize the users\u2019 (children with and without disabilities) perspectives on environmental qualities that enhance their play experiences in community playgrounds. Published peer-reviewed studies were systematically searched in seven databases from disciplines of architecture, education, health, and social sciences; 2905 studies were screened, and the last search was performed in January 2023. Included studies ( Play is a fundamental right of children that is essential for health, well-being, and development, as stated in article 31 of the United Nations Convention on the Rights of the Child (UNCRC) experiences to gain insight into what environmental qualities maximize the play experience in public playgrounds for all children.A three-step search strategy was undertaken. First, an initial search helped identify relevant articles and other key search terms. Second, a test search in one database with an initial search string was performed. In this phase, information specialists from the University College Cork library were consulted to validate the search string and strategy. Third, the systematic search using the revised search string was conducted in August 2021; a follow-up-search was performed January 2023. See The systematic search of peer-reviewed studies was conducted in seven databases relevant to the disciplines of health, education, social sciences, and architecture, which allowed a broad range of literature for different professional audiences to be included. No limitations were set for publication year. The executed search string see was builThe two-step review process involved scanning titles, abstracts, and full texts. All citations were transferred into the online review software COVIDENCE . DuplicaAs recommended by Levac et al. , two phaThe second phase included a convergent synthesis design using the same content analysis on qualitative, quantitative, and mixed-method studies . The quaThe findings where charted and summarized by the first author (T.M.). First, the scope of the included studies is summarised. In the second part, themes from the qualitative content analysis are presented. In approaching this review from a children\u2019s perspective, including children with and without disabilities, the findings only elaborate on a specific population when findings were only found for that specific population.The searches revealed a total of 6095 references, which was reduced to 3190 after duplicates were removed. Articles were reduced in two rounds of title and abstract scans first to 503 studies and, after refinement of the inclusion criteria, to 104 studies. Full text reviews identified 49 studies meeting the inclusion criteria see . Two addn = 25), Australia and New Zealand (n = 11), followed by Asia (n = 8) and North America (n = 7). No studies from Africa or South America met the inclusion criteria (See A detailed description of the included papers can be found in eria See .n = 16), Education (n = 15), Occupational Therapy (n = 6), Psychology (n = 4), Exercise, Sport and Nutrition Sciences (n = 4), Human Geography (n = 3), Occupational Science (n = 1), Public Health (n = 1), and Practitioner Researcher (n = 1). Interdisciplinary contributions to the topic came from Architecture and Landscape Architecture (n = 30) methods, followed by quantitative (n = 13) and mixed methods (n = 8). Most studies used multiple data collection methods (see n = 23), focus groups (n = 10), walk-along talks (n = 10), and observational methods referred to as systematic (n = 11) and unsystematic (n = 9).Most papers employed qualitative , suburban (n = 6), rural (n = 6), and mixed (n = 2) areas. Location was missing in ten studies, and in two studies a reported location was not relevant to the study aims. Playgrounds were located in community areas such as playgrounds in parks or specific playground spaces (n = 27), schools (n = 16), or both public and school playgrounds (n = 3). Two of the papers looked at adventure playgrounds [In total, 212 playgrounds were represented. The locations of playgrounds were reported in urban male, 35.3% (n = 1299) female, and 29.8% (n = 1095) unreported sex. Six observational studies provided observation counts but not participant numbers [The total participant sample included numbers ,95,101, numbers . The stuOnly ten studies included children with disabilities, representing a sample of 125 participants . Of these, four studies focused on children with disabilities only ,68,102, Fifteen studies also included other participants along with our population of interest, for example, parents and other family members, teachers, playground maintenance staff, play workers, or health professionals ,99,102. Five themes were identified that provide insight into the interconnection between play experiences and the environments that enhance outdoor play see . These fdiverse intense and novel play experiences, which related to engagement in intensified movements and intensified sensory experiences finding suitable challenges, (2) using the environment flexibly, and (3) having moments to unfold their own play. This theme synthesises evidence of what the physical and social environment provided for children, especially in the context of having permission to self-direct their own play.suitable challenges in their playgrounds [Children reported the importance of having ygrounds ,78,84,88ygrounds and needygrounds ,84. Thisygrounds ,61,63 thygrounds ,94,102. ygrounds ,77,102. ygrounds ,68. In sygrounds . This maygrounds .Using the environment flexibly meant exploiting any possible way to engage with play equipment and other built structures beyond their intended use [nded use ,92,101. nded use ,71,79,80nded use ,59,65 ornded use ,67,88, bnded use ,59, jumpnded use , or hangnded use . Other cnded use ,65,67. Anded use ,71,89 ornded use ,78,84,92nded use , and anynded use ,75,76. Bnded use ,63,75; tUnfolding own play was linked to social and physical environmental qualities. This was accomplished by having uninterrupted moments to unfold own play afforded by the physical and social environment. The physical environment meant having a suitable space and objects affording children to engage in their unfolding play. The social environment meant adults (and other people) granting permission for children\u2019s own play. Across studies, children or children\u2019s groups provided examples of their unfolding play in correspondence to their particular physical and social environment [ironment ,76,81,88ironment ,70, fly-ironment , jumpingironment , needle-ironment , or raceironment . Sometimironment ,78,91,94ironment , being-aironment , the-floironment , being-dThis subtheme describes the evidence showing that children value and seek opportunities to engage with a diversity of people and animals while also wanting to play by themselves, especially when playing away from adults offers treasured play experiences. Playing with children was a key component described as enhancing children\u2019s play experiences. Examples included swinging together with one particular friend [r friend ,78, rollr friend , climbinr friend , crashinr friend ,64, or hr friend ,67,68. Cr friend ,84,88,91r friend ,91,101. r friend . Similarr friend . The phyr friend ,60,67,68r friend ,79,84,95r friend ,64,82, or friend ,72,92,96Playing with adults occurred in the presence of supportive adults who knew how and when or when not to intercede with children\u2019s play. This was perceived in three ways. First, adults were actively involved in the same play together with the children [Adults who accompanied children influenced their play ,67,88. Pchildren ,64,84,88children or playichildren ,68,71. Schildren . This wachildren ,73. The children . Third, children ,61,67,88children ,67,68,84Being away from adults and other children was about the experience of not being seen and showed a connection with the theme of choices and self-directed play. Children referred to being away from adults more frequently than they did being away from other children. Being away from adults was associated with privacy, having secrets, and breaking the rules. This was possible in places in the natural and built environment that afforded privacy and seclusion, such as small spaces [l spaces ,76,81,96l spaces ,76,78,94l spaces ,64,75,76l spaces ,64,67,75l spaces ,75,81, al spaces ,64,81. Il spaces , such asl spaces ,76,84, fl spaces ,84, diggl spaces , wanderil spaces ,64,75 lil spaces , or entel spaces ,67,76,84Both physical and social environmental qualities influenced children\u2019s feelings of connection with their playgrounds. Belonging to their playground was experienced by (1) being familiar with the playground, (2) feeling welcome and safe, and (3) enjoying playground aesthetics.Feeling connected with the playground had relational qualities, including knowing the playgrounds located in the home community [ommunity ,58,61,66ommunity ,70,78, aommunity ,72,73,78ommunity ,74,77,81ommunity ,66,79. Hommunity ,55,61,68ommunity ,81,96.feel welcome and safe in playgrounds, especially children with disabilities who wanted a welcoming atmosphere created by accessible and usable playground design that afforded play with others [Children wanted to h others ,61,67,68h others ,102. Welh others ,68,72. Rh others ,80, peoph others , caring h others ,64,80, oh others . Similarh others ,80 or whh others . Whetherh others or gave h others . Howeverh others ,83,85. perceptions of aesthetics and beauty in the built and natural environment. Children wanted to play on appealing playgrounds. Playgrounds were unattractive and ugly when they were dirty; smelled bad; were littered with glass, needles, cigarette butts, duck and dog excrement; had graffiti; or were noisy and overcrowded [The connection to playgrounds was strengthened by children\u2019s rcrowded ,78,84,92rcrowded ,78,82,89rcrowded ,67,80,84rcrowded ,75,76,89rcrowded ,84,85. Trcrowded ,94. Naturcrowded ,78,84, ircrowded ,64,78,81rcrowded ,64,91 anrcrowded ,88,94. Arcrowded ,70,75,76rcrowded ,81. experience of fun was the overarching and core experience in outdoor play. Children actively sought more fun in play. Fun evolved while playing but was also anticipated when children engaged in play and was sometimes described as a prerequisite for play [The for play ,61,84. Cfor play . The expFor the physical environment, this was interwoven with providing intense play opportunities ,57,59,84The social environment included having people and animals available to play with ,55,61,81Fun was contrasted to the boredom experienced when the playground did not provide a sufficient diversity of play opportunities in the built and natural environment ,70,79,84children\u2019s place. These findings point to the importance of acknowledging children\u2019s perspective\u2019s, regardless of ability, in playground provision, design, and evaluation.This scoping review aimed to summarize the experiences of children with and without disabilities, and to gain insight into environmental qualities that maximize play experiences for all children on community playgrounds. There were two key findings. First, this review showed that the combined qualities of the physical and social environment afforded play experiences that children preferred and desired when engaging in outdoor play. This interconnection was sometimes linked to certain environmental qualities relating only to the physical environment or only to the social environment, but more commonly related to both the social and physical environment combined. Second, the review revealed children were knowledgeable about their community playgrounds and environmental qualities that contributed to enhancing their outdoor play experiences. These play experiences were multifaceted and included having opportunities for fun and intense motor and sensory play, engaging in suitable challenges, making choices, and having moments to unfold their own play. Children valued a spectrum of play, from playing alone, to playing in small to big groups of peers and friends, and playing with adults and animals. Children also desired safe, welcoming, and aesthetically pleasing playgrounds where they felt they belonged as they knew other users and the playground. In other words, community playgrounds with the best play value become a children\u2019s places that went beyond simply being a place to play.This review presented rich and varied information about how children utilised physical and social environmental affordances available to them. Environmental affordances have been successfully used in outdoor play research to understand how children perceive and use their environments for outdoor play ,103,104.The findings of the review confirmed a persuading agency of the physical environment on affordances that children perceive and actualize in outdoor play. Persuading agency refers to the power the environment has to entice children to play. In this review, the understanding of affordances was broadened, as children did not only perceive action possibilities ,103,104 Intersections between the physical and social environmental qualities were found to contribute to the overall atmospheric and more tacit atmospheric affordances of playgrounds. Children elaborated on these atmospheric affordances in their experiences of feeling safe and welcomed and their perception of aesthetics. A physical environment that is aesthetic, colourful, clean, and contained both built and natural play opportunities contributes to an environment that is appealing to children. Loebach and Gilliland found thIn this review, social affordances were not only related to those with whom children played, such as children, adults, or animals. Children, regardless of ability, emphasised their relationship to significant play partners such as children and adults they knew, such as friends from school and the proximate neighbourhood, known people from the community, and known peers with similar abilities and interest, or of the same sex. This concept of knowing others also transcended to the physical space, as if the playground was a friend as well. Children wanted to feel connected to their playground through positive play experiences either alone or with known people who were associated with the playground. These findings indicate that playgrounds have the potential to be spaces for social inclusion ,29. SuppFurther social affordances in this review were related to social rules and practices such as having permission to use built environments flexibly, having uninterrupted moments to unfold own play, and having opportunities to play away from adults and solely with peers. Both children with and without disabilities valued opportunities to self-direct their play an expressed the wish for less adult interference and surveillance. However, such opportunities were identified differently by children with and without disabilities and depended on different physical and social environmental qualities in combination. For children with disabilities, adult permission needs to be discussed, since these children frequently reported needing adult assistance due to inaccessible and unusable physical environments ,102,112.The review findings provide synthesized evidence of children\u2019s perspectives on the outdoor play experiences they value and prefer in community playgrounds, helping to identify environmental qualities that provide for such experiences. Aligning with other studies ,30,33,72The findings need to be interpreted with the following considerations. First, parents\u2019 and caregivers\u2019 perspectives were not included. These would provide an additional viewpoint for understanding children\u2019s play experiences. Future research might investigate both the perspectives of parents and children to provide insight into how these differ. Second, the included studies encompassed community and school playgrounds as the units of analysis. This inclusion criterion was set because, for some countries, school playgrounds are open to the public during non-school-hours. In this review, most studies of school playgrounds did not specifically state if a school playground was open to the public or not. However, some included study data were collected during school times. Third, a methodological quality assessment might strengthen the interpretation of the study findings. However, a methodological quality assessment was omitted due to the interdisciplinary scope of the research and the variety of methodologies and methods used. A scoping review was considered a suitable methodology in the interdisciplinary area of playground research, and the inclusion of publications from a diversity of disciplines strengthened the findings. This review was able to link play experiences to environmental qualities by synthesizing findings from peer-reviewed articles using qualitative, quantitative, and mixed methods. The most useful information regarding children\u2019s perspectives was collected through multiple methods, including verbal accounts and observations. Most of the studies relied on qualitative methodologies. This highlights the need for instruments to allow investigations into children\u2019s perspectives in a more systematic way and consider the conjunction between children\u2019s experiences and environments. Future research should investigate environmental qualities such as those found in this scoping review to elicit potential affordances for play experiences available to children with and without disabilities. A further gap in research was identified in the representation of perspectives in research. Only ten studies included children with disabilities; of these, only six studies included children with and without disabilities in combination. If playgrounds are places for inclusion, research and practice need to take a more diverse perspectives into consideration in playground provision, design, and evaluation.This scoping review aimed to synthesise play experiences of children with and without disabilities and gain insight into what environmental qualities contribute most to enhancing play experiences in community playgrounds. Gaps in research were identified in the limited number of papers that included both children with and without disabilities, in the lack of research about how community playgrounds can provide more access to nature for all children, regardless of ability, and the need for instruments that investigate the connection between children\u2019s experiences and environments. The main findings of this scoping review were as follows. First, the available evidence allows an understanding of how the combined social and physical environmental qualities of playgrounds enhance outdoor play experiences by providing a diversity of experiences. Multifaceted play experiences were reported with the desire for fun, challenging, and intense play; the wish for self-directed play; opportunities to play alone and with known social partners; and a desire for welcoming, safe, and aesthetically pleasing playgrounds. Second, regardless of ability, children were knowledgeable about the play value of their community playgrounds, and therefore, their perspectives need to be more closely considered. Playground provision, design, and evaluation needs to move beyond merely providing dedicated spaces for play and consider instead, provisions for potential outdoor play experiences that allow playgrounds to become children\u2019s places. This means that children\u2019s preferences and what children want to experience in playgrounds need to be at the heart of playground provision, design, and evaluation."} +{"text": "This popular annual session will provide cutting-edge information on what the 117th Congress has and has not accomplished to date, and what may be left for the lame duck session to address. Speakers will discuss key issues such as Social Security, Medicare, Medicaid, Older Americans Act, Build Back Better Act, social isolation, serious illness care, and funding. Predictions for the 118th Congress may be provided."} +{"text": "Globally, blood pressure management strategies were ineffective, and a low percentage of patients receiving hypertension treatment had their blood pressure controlled. In this study, we aimed to build a medication prediction model by correlating patient attributes with medications to help physicians quickly and rationally match appropriate medications.We collected clinical data from elderly hypertensive patients during hospitalization and combined statistical methods and machine learning (ML) algorithms to filter out typical indicators. We constructed five ML models to evaluate all datasets using 5-fold cross-validation. Include random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), artificial neural network (ANN), and naive Bayes (NB) models. And the performance of the models was evaluated using the micro-F1 score.Our experiments showed that by statistical methods and ML algorithms for feature selection, we finally selected Age, SBP, DBP, Lymph, RBC, HCT, MCHC, PLT, AST, TBIL, Cr, UA, Urea, K, Na, Ga, TP, GLU, TC, TG, \u03b3-GT, Gender, HTN CAD, and RI as feature metrics of the models. LightGBM had the best prediction performance with the micro-F1 of 78.45%, which was higher than the other four models.LightGBM model has good results in predicting antihypertensive medication regimens, and the model can be beneficial in improving the personalization of hypertension treatment. Hypertension is one of the most common chronic diseases and a significant risk factor for cardiovascular disease, chronic kidney disease, cognitive impairment, all-cause mortality, and disability . TherefoMaintaining appropriate blood pressure is a critical strategy for lowering the incidence of cardiovascular illness, disability, and mortality. Nowadays, the treatment options for hypertension mainly include life interventions and pharmacological treatment. The common antihypertensive drugs can be divided into five categories: angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARB), calcium channel blockers (CCB), \u03b2-blockers, and diuretics. According to the biggest research ever conducted on hypertension, between 1990 and 2019, fewer than one-quarter of hypertensive women and one-fifth of hypertensive men could regulate their blood pressure to normal levels with medication . The WorElectronic Health Record (EHR) is the digitization of an individual's health record. It contains patient data collected during clinical care, including diagnostic billing codes, procedure codes, vital signs, laboratory test results, clinical imaging, and physician records. In recent years, the EHR has become a centerpiece of hospital information systems as healthcare information technology continues to evolve and the demand for clinical and record information management surges. EHR data are used in various applications, including epidemiological and observational studies, safety surveillance and regulatory use, and prospective clinical studies. Examples: Tabesh et al. analyzed+, FPG, and LDL also impacted Irbesartan; Metoprolol was affected by Age, Urea, and HCT; Felodipine was affected by FPG, Age, and HB; and Amlodipine was affected by FPG, Age, and Urea. Liu et al. , coronary artery disease (CAD), diabetes, stroke, and renal insufficiency (RI). In the beginning, 47 indicators were chosen from the clinical tests based on the recommendations of specialists. However, certainly expected indications were absent from the majority of samples. In addition to the fact that professionals pay more attention to the essential characteristics during real diagnosis and therapy, we ultimately chose 22 attributes. The 22 attributes were: glucose (GLU), total cholesterol (TC), triglycerides (TG), potassium (K), sodium (Na), calcium (Ca), creatinine (Crea), serum uric acid (UA), serum urea (Urea), aspartate aminotransferase (AST), alanine aminotransferase (ALT), \u03b3-glutamyl transpeptidase (\u03b3-GT), total bilirubin (TBIL), total protein (TP), red blood cell (RBC), hematocrit (HCT) level, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), lymphocyte (Lymph) count, platelet (PLT) count, and mean platelet volume (MPV). The standard reference ranges for blood pressure and laboratory indices were listed in 2-test was used to compare groups. P < 0.05 was considered a statistically significant difference. For the algorithm, we relied on Python (version 3.97).We used SPSS 26.0 and Excel 2013 software for statistical analysis. Kolmogorov-Smirnov was used to test data normality. x \u00b1 s expressed the normal distribution, and the comparison between groups was performed by analysis of variance. The non-normal distribution data were described as M , and the Kruskal\u2013Wallis test was used to compare groups. The categorical indicators were expressed by rate (%), and the \u03c7In this study, we used five ML algorithms for feature selection, namely Pearson correlation coefficient, Lasso, maximum information coefficient (MIC), random forest (RF), and recursive feature elimination (REF). The five ML models were built into an ensemble model according to specific rules. Finally, combined the ensemble model with statistical analysis to obtain the final feature indicators. For a better comparison, values of all attributes were Min-Max normalized to a standard range using the following formula:Normalized value = / We compared the performance of RF, SVM, LightGBM, ANN, and NB, which are all well-known ML classification algorithms, to find the best model for predicting medication use. To segment the data for each algorithm, we used a 5-fold cross-validation approach, trained the model through the training set each time, and validated the model's performance on the test set data. Due to the imbalance between the three predicted medication classes in this study, we used micro-F1 to assess the model's efficacy. Higher values of micro-F1 indicated better model performance, and it can be used for both multi-class classification problems and asymmetrical data. The calculation is as follows (for three categories):TPi refers to a true positive of class i; FPi refers to a false positive of class i; TNi refers to a true negative of class i; FNi refers to a false negative of class i.The flow chart of the data process and analysis is shown in We looked up \u201c2016.12-2021.12, age \u226565 years, primary hypertension\u201d on the MeduCloud platform to get a sample of 51,895 cases. Firstly, we excluded 14,950 cases that did not register the use of antihypertensive drugs. Secondly, removed 10,884 cases lacked blood pressure and laboratory test records. Finally, deleted 15,043 cases that did not have complete records of 26 clinical indicators. After data cleaning, 11,018 cases were left. In light of the actual situation, we selected three more frequent drugs for studying. They were 110 cases of Perindopril, 1,542 cases of Amlodipine, and 519 cases of Furosemide . MeanwhiP = 0.000), and the age of patients in the group using Furosemide [79.00 ] was higher than in the other two groups [74.00 ]. In laboratory tests, there were significant differences in SBP, DBP, Lymph, RBC, HCT, MCHC, PLT, AST, TBIL, Cr, UA, Urea, K, Na, Ga, TP, GLU, TC, TG, and \u03b3-GT . Men use Amlodipine and Furosemide more frequently than women, and in contrast, women use Perindopril more regularly than men. Among previous disease history, there was a statistically significant difference in HTN , CAD , and RI .The purpose of feature selection is to pick a set number of feature subsets that provide the least generalization error on the original sample or to decide the smallest feature subset possible under a given generalization error . ApplyinWe recorded the feature ranking obtained by each algorithm. The higher the ranking number, the more influential the feature was.We found the average order of each feature under the five algorithms.We calculated the weight corresponding to the ranking average.According to the algorithm analysis, Lymph, Urea, HCT, TC, Na, TP, RBC, TBIL, K, SBP, Age, TG, UA, and AST were the essential features affecting the selection of medication for hypertension. The outcomes of the above feature selection procedures were summed together, with deeper colors indicating more crucial features .Combine statistical analysis with ML feature selection, where 1 (dark red) indicates that this feature is considered important by both statistics and algorithms, and 0 (light white) indicates that it is not regarded as relevant by either. If the algorithm does not value a feature, but the statistics do, we have a 0.5 (light red) feature, and vice versa .In order not to omit the information related to the medication regimen, in the subsequent analysis, we still choose Age, SBP, DBP, Lymph, RBC, HCT, MCHC, PLT, AST, TBIL, Cr, UA, Urea, K, Na, Ga, TP, GLU, TC, TG, \u03b3-GT, Gender, HTN, CAD, RI as feature indicators.On the basis of these indicators, we built five ML models. We ranked the significance of all variables in the LightGBM model to comprehend the role of each better. The findings revealed that the five most critical characteristics of the model, TP, TBIL, Na, Lymph, and UA, contributed considerably to the prediction outcomes .We also figured out the saprophytic additivity explanation (SHAP) values of the LightGBM for different types of drugs to find the most important factors that drive model predictions. Previous research has extensively discussed the significance of medication , 25. HowAmlodipine belongs to CCB, and several international, large-scale clinical investigations have proved its safety and efficacy in middle-aged and older populations. These studies include VALUE, ALLHAT, and ASCOTA \u201330. It aP < 0.05), suggesting that secondary erythrocytosis occurs in hypertensive patients and may induce an increase in blood viscosity. The MPV of the hypertensive group was lower than that of the control group (P < 0.05), indicating that evaluating PLT and platelet parameters might be employed as hypertension preventive and therapy detection indications in the elderly. Blood potassium, sodium, liver and kidney function, blood glucose, lipids, and other factors are all examined in blood biochemistry. If the test results show low blood potassium, secondary hypertension is possible. The detection of blood glucose and blood lipids may assist in determining if there are additional risk factors for cardiovascular and cerebrovascular disorders, and the evaluation of liver and kidney function is beneficial for physicians to pick antihypertensive drugs according to the patient's state. The results of these blood test indicators affect the choice of antihypertensive drugs and may guide the treatment of hypertension.Hypertension generally causes kidney, heart, and other disease abnormalities, and antihypertensive medications may alter liver function. As a result, hypertensive patients usually need their blood routine, blood biochemistry, liver and kidney function, cardiac enzymes, and other items tested. Based on the literature reports , 34, cliDespite the fact that there are defined clinical guidelines for the management of hypertension, there is still some confusion about how to treat hypertension. Therefore, we develop individualized medication by determining which characteristics influence drug selection. Our results showed that Age, SBP, DBP, Lymph, RBC, HCT, MCHC, PLT, AST, TBIL, Cr, UA, Urea, K, Na, Ga, TP, GLU, TC, TG, \u03b3-GT, Gender, HTN, CAD, and RI were the typical indicators of the model. And among them, TP, TBIL, Na, Lymph, and UA were the five main indicators of LightGBM, which critically affected the selection of antihypertensive drugs. Wei et al. discoverWe compared five ML algorithms, and all were tested using a 5-fold cross-validation approach. In our study, the LightGBM model had a micro-F1 value of 78.4%, significantly higher than the other four ML models. These results demonstrate the superiority of the LightGBM model for determining which antihypertension drugs will be most effective in the elderly. LightGBM is an integrated model of decision tree for classification and regression prediction. It has an excellent version in disease diagnosis, such as Rufo using LiUndoubtedly, the findings of this research have provided some groundwork for the following study. However, the current research does have a few limitations. This research is retrospective, and there is bias in the data, which is an issue that arises in all retrospective studies. On the other hand, the treatment of hypertension in clinical practice is mainly based on administering many medications in conjunction with one another. Only three kinds of single-drug modeling with greater frequency were chosen for the prediction investigation in this particular research, which is obviously not enough. In the following sections, we will discuss the multi-label classification, which may accurately forecast various treatment regimens.This study constructed a single-drug prediction model for antihypertensive drugs based on SVM, RF, LightGBM, ANN, and NB algorithms. And we also compared the efficacy of the model with evaluation metrics such as accuracy, recall, and micro-F1 to reduce the bias caused by a single algorithm and a single evaluation metric to some extent. The results showed that LightGBM predicted the best results compared with other algorithms, with a micro-F1 value of 78.4%. We also used feature importance ranking and SHAP values to enhance the interpretability of the model. We suggest that \u201cincreased Na, TBIL, and Ca, and decreased \u03b3-GT and TC\u201d can be prioritized for Perindopril, and \u201chigher ALT and SBP, lower AST, TBIL, and Urea\u201d can be prioritized with Amlodipine, \u201chigher levels of UA, low levels of SBP, Lymph, HCT, and Na\u201d can be prioritized for Furosemide. The study included patients from multiple medical institutions, and the study's results may help clinicians provide decision support in prescribing antihypertensive drugs to patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.TW and WZ contributed to the conception and drafting of the study. YY helped to develop new techniques and programs. Data analysis by TW, SX, JT, and CY. The final text was reviewed and approved by all writers.This study has been financially supported by the College of Medical Informatics, Chongqing Medical University, China, Student Research and Innovation Experiment Project (YJSZHYX202120).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "This study describes the global epidemiology and trends associated with neck pain. Global Burden of Disease data collected between 1990 and 2019 were used to determine the global burden of neck pain in the general populations of 204 countries.Global, regional, and national burdens of neck pain determined by prevalence, incidence, and years lived with a disability (YLD) from 1990 to 2019 were comprehensively analyzed according to age, gender, and socio-demographic index using the Global Burden of Disease Study 1990 and 2019 data provided by the Institute for Health Metrics and Evaluation.Globally, in 2019, the age-standardized rates for prevalence, incidence, and YLD of neck pain per 100,000 population was 2,696.5 , 579.1 , and 267.4 per 100,000 population, respectively. Overall, there was no significant difference in prevalence, incidence, or YLD of neck pain between 1990 and 2019. The highest age-standardized YLD of neck pain per 100,000 population in 2019 was observed in high-income North America , Southeast Asia , and East Asia . High-income North America had the largest increases in YLD of neck pain per 100,000 population from 1990 to 2019. At the national level, the highest age-standardized YLD of neck pain was found in the Philippines and the highest change age-standardized YLD between 1990 and 2019 was found in the United States . Overall, the global burden of neck pain increased with age until the age of 70\u201374 years, and was higher in women than men. In general, positive associations between socio-demographic index and burden of neck pain were found.Because neck pain is a major public health burden with a high prevalence, incidence, and YLD worldwide, it is important to update its epidemiological data and trends to cope with the future burden of neck pain. Neck pain is a common pain that occurs in the human body and causes not only pain but also neck pain disability and economic problems . In 2016With the increase in global aging, the prevalence and incidence of neck pain are also presumably increasing. Knowledge of the global burden of neck pain could aid in the prevention and/or management of patients at high risk of neck pain and inform policy decision making at the national level.The present study aimed to investigate the global, regional, and national burden of neck pain including prevalence, incidence, and years lived with disability (YLD) between 1990 and 2019 according to age, gender, region, and country, based on analysis of GBD information provided by the Institute for Health Metrics and Evaluation (IHME). An additional aim was to investigate the burden of neck pain based on socio-demographic index (SDI), which reflects the development level of individual countries.The GBD Study is a systematic and comprehensive study of diseases worldwide. Based on data generated in this study, it is possible to compare and analyze the global, regional, and national burdens of diseases . GBD Stu*,\u201d and \u201cinciden*\u201d . From thta.org/) . GBD 201ta.org/) , 16\u201318.In the GBD Study, neck pain is defined as pain occurring in the cervical spine and lasting for at least 24 h, regardless of accompanying referred pain in both arms. The anatomical location of neck pain is defined based on the definition recommended by the Bone and Joint Decade 2000\u20132010 Task Force on Neck Pain and its Associated Disorders . In the The GBD of neck pain was evaluated as incidence, prevalence, death, disability-adjusted life years (DALYs), YLDs, and years of life lost due to premature mortality (YLLs) . DALYs wTo investigate the association between the level of development of regions or countries and neck pain disorder, the SDI was utilized . SDI is Prevalence, incidence, and YLDs of neck pain for both genders for 2019 are presented in High-income North America , Southeast Asia , and East Asia had the highest age-standardized point prevalence, annual incidence, and YLD of neck pain per 100,000 population in 2019, respectively. Conversely, Australasia , Central Sub-Saharan Africa , and Eastern Sub-Saharan Africa had the lowest age-standardized point prevalence, annual incidence, and YLD of neck pain per 100,000 population in 2019, respectively . Age-staAge-standardized point prevalence of neck pain per 100,000 population in 2019 was highest in the Philippines , United States , the United Kingdom , and lowest in New Zealand , Australia , and Djibouti .Countries with the highest age-standardized incidence of neck pain per 100,000 population in 2019 were the Philippines , Indonesia , and the United States , whereas New Zealand , Australia , and Djibouti had the lowest rates .Philippines , the United States , and the United Kingdom had the highest age-standardized YLD of neck pain per 100,000 population in 2019, whereas New Zealand , Australia , and South Sudan had the lowest rates .Percentage change in age-standardized point prevalence (ASPP), annual incidence (AI), and YLD of neck pain per 100,000 population from 1990 to 2019 differed between countries. The largest increases were in the United States , Malaysia , and Nigeria , respectively. In contrast, New Zealand , Norway , and Taiwan showed the largest decreases .Age-standardized YLDs (number and rate) for neck pain according to age and gender are presented in In a previous study , the relWe reported the prevalence, incidence, and YLD of neck pain at the global, regional, and national levels from 1990 to 2019 and presented the age-standardized number and rate of YLD in 2019. The prevalence, incidence, and YLD of neck pain in 2019 were not significantly different from those in 1990. The global age-standardized prevalence of neck pain was 4.9% (95% CI 4.6 to 5.3) according to analysis of 2010 GBD data, 3,551.1 per 100,000 (95% UI 3139.5 to 3977.9) according to analysis of 2017 GBD data Compare Viz Hub, The studies involving human participants were reviewed and approved by Institutional Review Board at Ewha Womans University Seoul Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.DS, JS, YC, and T-JS contributed to conception and design of the study. HL and T-JS organized the database. DS, HL, and T-JS performed the statistical analysis. DS and T-JS wrote the first draft of the manuscript. DS, JS, AK, LJ, LS, YC, and T-JS wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.This project was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education . The funding source had no role in the design, conduct, or reporting of the study.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Essentially, the second author, Qi-Jin Feng, requested that they be removed from the paper due to disagreements over the interpretation of certain of the experiments. All the authors agree to the indicated change of authorship on this paper, and agree with the publication of this corrigendum. Therefore, the revised authors\u2019 names on this paper, together with their affiliations, are as follows:1*, GUI-SHI LI2, PENG SHEN3, YA-NAN LI4 and FU-JIANG ZHANG1WEN-BIN LIU1Department of Joint Surgery, Tianjin Hospital, Tianjin 300211; 2Department of Joint Surgery, Yuhuangding Hospital, Yantai, Shandong 264000; 3Department of Rheumatology and Immunology, Tianjin First Center Hospital, Tianjin 300192; 4Department of Orthopedics, Tianjin Dongli Hospital, Tianjin 300300, P.R. ChinaExperimental and Therapuetic Medicine for allowing them the opportunity to publish this Corrigendum, and apologize for any inconvenience caused.The authors are grateful to the Editor of"} +{"text": "The original article has been corrected.The article \u201cClinical guidelines for primary sclerosing cholangitis 2017\u201d, written by Hiroyuki Isayama, Susumu Tazuma, Norihiro Kokudo, Atsushi Tanaka, Toshio Tsuyuguchi, Takahiro Nakazawa, Kenji Notohara, Suguru Mizuno, Nobuhisa Akamatsu, Masahiro Serikawa, Itaru Naitoh, Yoshiki Hirooka, Toshifumi Wakai, Takao Itoi, Tomoki Ebata, Shinji Okaniwa, Terumi Kamisawa, Hiroki Kawashima, Atsushi Kanno, Keiichi Kubota, Masami Tabata, Michiaki Unno, Hajime Takikawa, PSC guideline committee Members: Ministry of Health, Labour and Welfare (Japan) Research Project, The Intractable Hepatobiliary Disease Study Group, was originally published Online First without Open Access. After publication in volume 53, issue 9, page 1006\u20131034 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to \u00a9 The Authors 2021 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit"} +{"text": "This study aimed to investigate the relevance of the study with the neutrophil count and lymphocyte count ratio (NLR), platelet count and lymphocyte count ratio (PLR), and red blood cell distribution width (RDW) in the prognostic evaluation of colorectal cancer patients. n\u2009=\u200956) and the colorectal polyp group (n\u2009=\u200950). Analysis of the survival impact factors of patients with carcinoma of the rectum, preoperative NLR, ROW, PLR, and prognostic relationship, and comparison of NLR, PLR, and RDW diagnostic rate and expression were performed. 143 patients with colorectal cancer from January 2016 to January 2019 were selected by our hospital, and then, other 143 cases of physical examiners as normal groups were selecting to proceed colonoscopic biopsy to diagnose 106 cases of precancerous diseases related to colorectal cancer. Among them were the inflammatory bowel group (P0.05). There was no link between gender, age, aetiology, pathological type, and prognosis in patients with colorectal cancer (P > 0.05). Multiple variables in patients with colorectal cancer are affected by tissue categorization (poor differentiation), TNM stages , lymph node metastases, NLR, ROW, and PLR (P0.05). When compared to solo NLR, Row, and PLR diagnostics, the combination diagnosis and malignancy rates were greater, and the differences were statistically significant (P0.05). Diagnostic sensitivity, specificity, and accuracy were greater when compared to single NLR, ROW, and PLR. When compared to the normal control group, NLR, ROW, and PLR have greater levels, and the differences are statistically significant (P0.05). The patient survival declines more slowly as PLR, NLR, and the severity of the condition rises. Tissue type, TNM stage, lymph node metastasis, NLR, RDW, and PLR had a predictive influence on patients with colorectal cancer ( NLR, ROW, and PLR combined diagnosis has high accuracy in colorectal cancer diagnosis, and the prognosis of patients with NLR, ROW, and PLR levels has a tight association; so, clinically, the above signs should be identified, and the optimal treatment time is grasped. The colorectal cancer is a higher incidence of malignant tumor disease. The mortality rate and incidence rate are high; therefore, the clinical exploration of effective methods diagnosis and the treatment is critical . StudiesNLR and RDW can reflect the system of anti-inflammatory response, tumor presence, invasion, metastasis, and recurrence, and NLR, PLR, and clinical response to the body promoted tumor and antitumor immune response' evaluation . Anothern\u2009=\u200956) and a colorectal polyp group (n\u2009=\u200950). 143 patients with rectal cancer, 76 males, 67 female, (53.6\u2009\u00b1\u20093.8) years old, tissue classification: 25 patients with low-differentiated patients, high, medium differential patients; onset: 45 cases of rectum, rising 39 cases of colon, 27 ethyl colon, 13 cases designed, and 19 cases. The research object agreed with the study; in the meanwhile, the research data are comparable (P > 0.05), and the hospital ethics committee agreed with the study. Informed consent was obtained from the patients who were participating.From January 2016 to January 2019, 143 colorectal cancer cases in our hospital were selected and other 143 cases were selected as the normal group, and colonoscopic biopsy was selected as 106 cases of precancerous lesions are related to colorectal cancer Among them were the inflammatory bowel disease group were observed. Following the completion of the detection, the PLR value is derived using the NLR and RDW detection results. Patients are followed up on for two years by WeChat, phone, and other means, and the patient's survival time is reported.The explosion factors affecting renal cancer patients include gender, age, tissue classification, pathogenesis, TNM stage, pathological type, lymph node metastasis, NLR, RDW, PLR, and other factors.In preoperative NLR, ROW, PLR, and prognosis, add up tissue classification (low differentiation), TNM stages (III and IV), lymph node metastasis, NLR, ROW, PLR, and other factors.Calculate the calculation rate of diagnosis examples of benign and malignant patients.Add up 0, 20, 40, 60, and 80 months to correspond to NLR, PLR, and RDW survival rate, respectively. PLR normal range is , gender, age, pathogenesis, and pathological type, which has no correlation with the prognosis of patients with colorectal cancer (P > 0.05) .P < 0.05) , TNM stages (III and IV), lymph node metastasis, NLR, ROW, and PLR ( < 0.05) .P < 0.05) .P < 0.05) .P < 0.05) .Patient survival rates are steadily dropping as PLR and NLR levels rise in conjunction with increasingly severe conditions .The detrimental degree of colorectal cancer is severe, affecting the normal life of the patient. The current clinical research hotspot is to explore accurate diagnosis methods, improve prognosis, and reduce the degree of harm to patients , 7. SeveP < 0.05). The main causes of RDW, NLR, and PLR affect the prognosis of colorectal cancer patients, the level of inflammatory factors increased, and the risk of colorectal cancer increased. Neutral granulocytes are N2 in the tumor state, which can pass base metal protease and vascular endothelial growth factor' effect on tumor cell apoptosis, which has promoted tumor angiogenesis, and tumor progression accelerates [P0.05), sex, age, disease location, pathological type, and prognosis of colorectal cancer patients have no correlation (P0.05). A comprehensive analysis should influence clinical prognostic factors in patients with colorectal cancer, and targeted interventions, with individual treatment, improve patient survival. The appraised value of research was analyzed using NLR, PLR, and RDW in the prognosis of patients with colorectal cancer and higher clinical feasibility, but this study is a retrospective analysis which included a limited number of cases. The accuracy of the results will have an impact. Following that, the sample should contain more qualified individuals who do a more in-depth investigation into immune inflammation; in order to increase the accuracy of research, lengthen the lifespan of the patient and improve the patient's quality of life.The study detected the value exploration of RDW, NLR, and PLR levels in colorectal carcinoma and analyzed the diagnosis, accuracy, and sensitivity. The results showed that there was a statistically significant significance for combined diagnosis and specificity and differences in combination diagnosis. The main reason is that Row is the platelet count and lymphocyte count ratio, and platelets can secrete due to secretion of P selector in adhesion, endothelial, and inflammatory cells, having promotion . Plateleelerates , 20. Lymelerates . In addielerates . PLR andelerates . The bodelerates . After telerates . Therefoelerates . In addiIn summary, in terms of diagnosis of colorectal cancer, NLR, ROW, and PLR combined diagnosis is with high accuracy, and prognosis of patient with high NLR, ROW, and PLR levels has a close relationship; so, clinically, the above indicators should be detected and grasped for the best treatment timing."} +{"text": "In the originally published article, there were errors each of the author affiliations.Affiliation 1 should have been presented as \u201cShanghai Center of Thyroid Diseases, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China\u201d, and not as \u201cShanghai Center of Thyroid Diseases, Shanghai, China\u201d.Affiliation 2 should have been presented as \u201cDepartment of Endocrinology and Metabolism, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China\u201d, and not as \u201cDepartment of Endocrinology and Metabolism, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine, Shanghai, China\u201dAffiliation 3 should have been presented as \u201cDepartment of Pathology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China\u201d, and not as Department of Pathology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine, Shanghai, China\u201d.The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "One of these, authored by the GBD 2015 Child Mortality Collaborators, addressed global, regional, national and selected subnational levels of stillbirths, neonatal, infant and under-five mortality, 1980-2015.th for neonatal mortality (A) with rates 140% higher than Chile, which had the lowest rate. For postneonatal mortality, Brazil ranked 13th with rates 120% higher than Chile, which was again the country with the lowest rate. However, the picture for the age stratum from one to four years (B) differed from the traditional infant mortality category of under one year of age, such that Brazil was in fifth place, after Chile, Uruguay, Costa Rica and Argentina.This same articleFrom this summary, readers can grade the quality of child health in Brazil over recent years. The Journal is calling for more articles discussing \u201cChild Health in Brazil\u201d."} +{"text": "Magnetoplasmonic permittivity-near-zero ( Plasmonic nanostructures are at the core of recent transformative breakthroughs in a diverse set of areas such as biosensing , waveguiaterials , promisiaterials ,14,15.p indicates that this MO effect only exists for p-polarized light) when the magnetization of the system (M) is flippedOn the other hand, magneto-optical effects in magnetophotonic nanostructures, i.e., nanostructures containing materials with magneto-optic (MO) activity , have be surface . Indeed,ly shown ,23,24.d) and d, d, and angle of incidence, Despite the advantages of MO-ondition . Contrar of data ,24. In aproblems ,26,27,28d) composed by Ag nanorods in alumina (Alz-axis here) are indicated by the subscripts \u2016 and \u22a5, respectively, withg oxides ,29 incident medium, commonly called prism, placed above a metallic thin film that is surrounded by the analyte medium on the opposite side. In this approach, there is an angle above which the surface wave excited by attenuated total internal reflection ) phenomenon matches the phase of the surface plasmon wave in the metallic surface. It is just under this last phase-matching condition that SPR excitation occurs in the prism-based mechanism. In contrast, we are interested in the use of an from air . Althougfrom air . In the shown in c,d used d and An SMM-based algorithm can be used to calculate the reflectances associated with Equation , the corEquation of Rp, the number of chromosomes that survive and pass to the next generation , we We discuss the optimization of the n from n, from where a perfect linear behavior can be seen. The corresponding sensitivity for this structure was found as n), which, as noticed to design magnetoplasmonic"} +{"text": "In the published article, there was an error in the author list, and authors \u201cMeiyu Guo, Zhenfang Yuan\u201d were erroneously excluded. The corrected author list, affiliations, correspondence, and citations appear below.1\u2020, Wenjun Ji1\u2020, Meiyu Guo2, Tieci Yi1, Jie Wang1, Minghui Bao1, Yusi Gao1, Han Jin1, Difei Lu3*, Wei Ma1, Xiaoning Han1*, Jianping Li1 and Zhenfang Yuan3Lihua Hu1 Department of Cardiology, Peking University First Hospital, Beijing, China2 Department of Hematology, Peking University First Hospital, Beijing, China3 Department of Endocrinology, Peking University First Hospital, Beijing, China*Correspondence:Difei Luludifei3142@163.comXiaoning Handr_hanxn@126.comAuthor contributions section, and authors \u201cMeiyu Guo, Zhenfang Yuan\u201d were erroneously excluded. The corrected author contributions section appears below.In the published article, there was an error in the MG, WJ, TY, JW, DL, WM, JL, ZY, and XH contributed in this patient care, diagnosis, and treatment. LH, MB, YG, and HJ collected the data. LH drafted this manuscript. DL, XH, JL, and ZY revised the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.Funding statement was erroneously included. The Funding statement has been removed from the published article.In the published article, a Ethics statement was erroneously included. The Ethics statement has been removed from the published article.In the published article, an In the published article, authors \u201cMeiyu Guo, Zhenfang Yuan\u201d were erroneously excluded from the Copyright section. The corrected Copyright section appears below.\u201cCopyright \u00a9 2022 Hu, Ji, Guo, Yi, Wang, Bao, Gao, Jin, Lu, Ma, Han, Li and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Forensic Science, Medicine and Pathology has changed in January 2022 [After nearly 15\u00a0years, the scientific Chief Editorial Team of First of all, we gratefully thank former Editor-in-Chief Roger W. Byard, former European Editor Michael Tsokos, and former North American Editor John Hunsaker III for their time and passion invested over the past 15\u00a0years in the journal \u2014 they have not only read, reviewed, and edited thousands of papers, they have also published extensively themselves and thus contributed to the reputation of the journal, too. Together with the Editorial Board, they made the journal what it is today.Secondly, we would like to thank the whole team at Springer, who gave us three \u201cnewcomers\u201d the opportunity to follow in these big footsteps. We will do our best.Forensic Science, Medicine and Pathology will continue to explore all aspects of modern-day forensics. The range of topics covered will continue to include international forensic science, medicine, nursing, and pathology, as well as toxicology, human identification, mass disasters/mass war graves, profiling, imaging and forensic radiology, forensic age estimation, policing, wound assessment, child maltreatment, sexual assault, anthropology, archeology, entomology, botany, biology, veterinary pathology, medical-historical forensic research, and DNA. We will continue to insist on high scientific quality of papers in fluent and sufficiently readable English language. We pay great attention to evaluating the mega-authorship reports and ask to limit the number of self-citations, particularly if not necessary.Now brought to the second-most important journal worldwide in forensic medicine with regard to its current impact factor by the former Editorial team, Mors auxilium vitae\u00a0(Death Is Help For The Living), and looking beyond the horizon is crucial in modern forensic medicine. Interdisciplinary questions arising in the daily autopsy routine can be addressed scientifically, and forensic medicine can contribute to walk new paths. Thus, we also welcome \u201coutside-the-box\u201d papers, i.e., scientific research from the interface of forensic medicine and other medical disciplines \u2014 there is a significant overlap between forensic medicine and several curative disciplines, especially after a second look [ond look \u20135. This ond look . How doeForensic Science, Medicine and Pathology will continue to present a balance of forensic research and reviews from around the world to reflect modern advances through peer-reviewed papers, short communications, meeting proceedings, new forensic textbook comments, and case reports. Furthermore, we will open the journal to answers to forensic questions that involve interfaces with other medical disciplines, especially with regard to complications arising from performed \u2014 or necessary, but omitted \u2014 medical procedures in the broadest sense. Forensic scientists are often involved in medical malpractice lawsuits, healthcare policy, and patient safety management. Therefore, the authors have the opportunity to discuss unusual adverse events, causes of medical malpractice, and the forensic medicine approach to such an interesting field of research. The dead can teach the living.The scientific future of forensic medicine comprises not only of forensic issues, but involves interdisciplinary cooperation. We intend to be a relevant part of this future \u2014 and we can achieve this goal solely with the help of you, the authors and reviewers\u00a0from all over the world!Priv.-Doz. Dr. med. Claas T. Buschmann, Kiel/L\u00fcbeck, GermanyEditor-in-ChiefProf. Dr. Biagio Solarino, Bari, ItalyAssociate EditorProf. Takahito Hayashi, Kagoshima, JapanAssociate Editor"} +{"text": "Lack of awareness of the disease is one of the most frequent symptoms (<80%) of schizophrenia, and it is accepted to have different aspects: cognitive, related to compliance, specific symptoms, and temporary. The detection of those dimensions of insight affected, allows to select and prioritize the objectives and therapeutic strategies to improve it.To develop a multidimensional scale for monitoring insight in schizophrenia patientsA scale with 9 insight dimensions has been developed: appreciation of symptoms, acceptance of the cause, clinical and functional repercussions, limitations and level of competence, expected evolution and prognosis, terapeutic, and other factors. risk of decompensation. Each dimension is weighted from 0-4 points, and the result is expressed numerically and graphically. The scale was administered to 60 patients with schizophrenia on three occasions. The initial one by two psychiatrists consecutively, and the third three months after stable treatment. Other clinical and sociodemographic variables were also collected.In the analysis, reliability, internal consistency, and intra- and interobserver reliability, logical, content, criterion and construct validity were assessed, obtaining satisfactory results in Cronbach\u2019s coefficients and Pearson\u2019s correlation (> 0.7 and > 0.8).The scale has good reproducibility, validity, sensitivity and utility characteristics, which allow its use in patients with schizophrenia.No significant relationships."} +{"text": "Historically, communicable diseases, such as HIV/AIDS, viral hepatitis, malaria, poliomyelitis, tuberculosis, influenza and, more recently, the coronavirus disease 2019, have been at the center of global health concerns and initiatives, as they are transmitted from one person to another with a variety of ways, easily spread across national borders, and threaten the lives of millions of people all over the globe. Nonetheless, it is the \u201cinvisible epidemic\u201d of non-communicable diseases (NCDs) that represents the world\u2019s leading cause of death [NCDs, also known as chronic diseases, are characterized by non-contagious nature, multiple risk factors, a long latency period, a prolonged temporal course, functional impairment or disability, and incurability . They arThe list of NCDs that impose heavy morbidity and mortality toll also includes neurological and mental health diseases , glaucoma and hearing loss, digestive diseases , musculoskeletal diseases , chronic kidney disease, autoimmune conditions, and others . Importantly, NCDs increasingly affect poor countries, deprived societies, and the poorest people within all nations, as the \u201cwesternization\u201d of lifestyle gradually takes its toll in low- and middle-income countries, population ages, and commercial pressures for unhealthy diets and harmful habits continue to exist . Indeed,The tragedy (and opportunity) is the fact that most NCD morbidity and mortality could be prevented or delayed, and millions of people could live longer, healthier and happier lives . SeveralImportantly, it is estimated that most NCD deaths can be prevented by eliminating the most important modifiable factors , particuNCDs will be the predominant global public health challenge of the 21st century . Health"} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cDepartment of Cardiology, Central Hospital of Shanghai Putuo District, Shanghai University of Traditional Chinese Medicine, Shanghai, China\u201d, it should be \u201cDepartment of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "BackgroundHuman blood is an essential human element for which no substitute has yet been discovered. This study aims to determine the causes of discarding blood and its components.Material and methodsA retrospective study of three years was performed in a tertiary care hospital blood bank. Data were retrieved from the various registers and analysed.ResultsDuring this study, a total of 3280 units, 1868 units, and 486 units of whole blood were collected in 2018, 2019, and 2020, respectively. It was observed that the discard rate of whole blood was 9.48%, 17.23%, and 43% in 2018, 2019, and 2020, respectively. The discard rate for components varied, such as for packed red blood cells (PRBC), it was 1.76% in 2018, 1.73% in 2019, and 3.03% in 2020, for fresh frozen plasma (FFP), it was 4.08% in 2018, 4.36% in 2019, and 2.20% in 2020, and for platelets, it was 43.08% in 2018, 31.56% in 2019, and 45.03% in 2020. A total of 311, 322, and 209 units of whole blood were discarded in 2018, 2019, and 2020, respectively. The total whole blood and blood components were discarded for various reasons such as undiagnosed sterility , quality control, underweight, hemolysis unit, expiry, and polycythemia.ConclusionThe wastage of stored blood and its components is inevitable. Still, it can be minimised by optimum utilisation and implementation of blood transfusion services (BTS) along with the education and training of blood bank staff. There are various reasons for the wastage of blood and its components, such as unscreened transfusion-transmitted diseases, sterility, storage, less bleeding, expiry, hemolysis samples and polycythemia. Self-regular audits, coordination between hospital and blood bank staff, proper storage and handling of blood units, strict donor selection and deferral criteria, along with appropriate history taking, will help minimise the wastage of blood or its components. Human blood is an essential element of human life and there is no artificial substitute for blood that has been discovered yet. As its availability is limited, blood transfusion services (BTS) play a vital role in any national health service delivery system. Thus, the availability of safe and adequate blood saves lives and prevents the wastage of this valuable resource. Human blood is categorised as a \u201cdrug\u201d under section 3(b) of the Drugs and Cosmetics Act 1940 in India -4. For mThis is a retrospective study conducted in the Department of Pathology of S. Nijalingappa Medical College and HSK Hospital and Research Center, Bagalkot, Karnataka, India, to find out the various causes of the discarding of blood and its components in the blood bank of a tertiary care hospital for three years from January 1, 2018, to December 31, 2020. The selection of blood donation was made according to the World Health Organisation (WHO) selection criteria. Data were retrieved from various registers like the donor register, discard register, transfusion-transmitted diseases (TTDs) register, and components preparation register. The rationale for discarding blood and its components was analysed.Components preparations and discard of blood bags were done according to standard operating procedures and guidelines laid by National Aids Control Organisation (NACO), India, and our blood bank guidelines. The present study includes blood units discarded for various reasons like TTDs, seroreactivity, expired components, less bleed, breakage, clotted bag, hemolysed samples, and units sent for quality checks (QC). At the same time, no exclusion criteria were followed for the selection of the samples.All data were analysed using IBM SPSS Statistics for Windows, Version 26.0 . All categorical data were represented as frequency and percentages.A total of 3280 units, 1868 units, and 486 units of whole blood were collected in 2018, 2019, and 2020, respectively. The various components such as packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets were prepared. In 2018, 3946 units of PRBC and FFP, along with 1408 units of platelets, were prepared. In 2019, 3577 units of PRBC and FFP and 1302 units of platelets were prepared. Similarly, in 2020, 2772 units of PRBC and FFP, along with 635 units of platelets, were prepared , hepatitis C virus (HCV), Venereal Disease Research Laboratory (VDRL), India), quality control, underweight, hemolysed unit, expiry, and polycythemia and average discard rates are shown in Table Similarly, a total of 844, 629, and 431 units of blood components were discarded in 2018, 2019, and 2020, respectively. The discard rate of blood components was highest and lowest in 2018 and 2020, respectively. Among all three components, platelets have a high discard rate for all three years of the 3280 units, 322 17.23%) of the 1868 units, and 209 (43%) of the 486 units of whole blood were discarded in 2018, 2019, and 2020, respectively. The average discard rate for whole blood in the present study was 23.23%, which was higher than in studies by Suresh et al. (5.7%), Bobde et al. (6.63%), Sharma et al. (4.46%), and Kanani et al. (3.5%) ,11,7..23% of tThe various reasons for the discard of blood are seropositive for transfusion-transmissible infections (TTI) like HIV, HBsAg, HCV, VDRL, India, testing for syphilis, sterility , less bleeding (underweight), expiry, hemolysed sample, and polycythemia -15. Our The limitation of our study was less bleeding/underweight blood bags because of phlebotomy failure like the collapse of veins, uneasiness, vomiting, perspiration, hematoma formation, and fainting during donation. Such blood bags are unsuitable for transfusion as there is a mismatch between the amount of blood collected and the anticoagulant used in the bag. Such collection usually happens in blood donation camps. It can be prevented by the proper selection of healthy donors, motivation of donors, and adequate training of phlebotomy staff . In the The wastage of blood and its components is inevitable, but it can be minimised by optimum utilisation and implementation of BTS along with the education and training of blood bank staff. There are various reasons for the wastage of blood and its components, such as sterility, storage, less bleeding, expiry, hemolysed sample, and polycythemia.\u00a0Self-regular audits, coordination between hospital and blood bank staff, proper storage and handling of blood units, strict donor selection and deferral criteria, along with proper history taking, will help minimise the wastage of blood and its components."} +{"text": "Neisseria gonorrhoeae, as laboratory tests may have low sensitivity. The case reinforces the importance of clinical diagnosis showing the triad, \u201ctenosynovitis, polyarthralgia, and dermatitis\",A 35-year-old man from Rio de Janeiro, reported painful skin lesions breaking out on his right hand, seven days prior, in addition to fever and pain while walking. He presented with no history of trauma, headache, dysuria, urethral discharge, any comorbidities or use of medication, and admitted engaging in unprotected sex in the previous month. On physical examination, he was normotensive, with normal heart rate, and febrile (39\u00b0C). Vesicles with hemorrhagic content were observed on an erythematous base in the palmar region and dorsum of the right middle finger . Arthral"} +{"text": "PLOS ONE Editors retract this article [The article because Additionally, after this article was published, it was noted that the names of Kexin Zhang and Changzhong Liu appear incorrectly in the author list. At the time of retraction, this article was republished to provide the correct names and citation.IUH, CL, ATKZ, and AMA did not agree with the retraction. AK, RI, KZ, SA, and AAH either did not respond directly or could not be reached."} +{"text": "Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still the most prevalent type of osteonecrosis with clinical relevance. In Brazil, bisphosphonate use is high but there is a lack of epidemiological studies on BRONJ. To determine the clinical profile of BRONJ in a Brazilian population through an integrative review. Integrative review of BRONJ in a Brazilian population. Cases and clinical research on Brazilians with BRONJ between 2010 and 2019, indexed in PubMed/MEDLINE, Scopus, Web of Science and LILACS were reviewed. Age, sex, type and time of bisphosphonate intake, administration route, related diseases, region of the BRONJ, diagnostic criteria, staging, triggering factor and type of treatment were analyzed. Fifteen articles on 128 subjects were included. Most patients were women (82.03%); the mean age was 63 years. Intravenous zoledronic acid was mostly used (62.50%), for breast cancer treatment (46.87%). The main localization of BRONJ was the mandible (54.68%), associated mainly with tooth extractions (45.98%). The diagnostic criteria were clinical (100%) and radiographic (89.06%), mostly in stage II (68.08%). The surgical treatments were sequestrectomy (37.50%) and platelet-rich plasma (PRP) (36.71%). Microbial control was done using chlorhexidine (93.75%) and infection control using clindamycin (53.90%). BRONJ had higher prevalence in Brazilian women receiving treatment for breast cancer and osteoporosis. The mandible was the region most affected with a moderate stage of BRONJ, particularly when there were histories of tooth extraction and peri-implant surgery. Sequestrectomy with additional drugs and surgical therapy was the treatment most accomplished. Therefore, bone remodeling and deposition of physiological bone matrix are also affected.,,,,,,,,,In 2014, there was a change in the nomenclature for this disease, to take into account its relationship with other drugs. The names currently used follow the pattern [medication]-related osteonecrosis of the jaw. This relates to the use of anti-resorptive and antiangiogenic medications,Although, as mentioned before, other medications relating to maxillary osteonecrosis do exist, BPs are still the most relevant drugs in relation to osteonecrosis of the jaws.The clinical profile of BRONJ and treatment protocols can vary according to specific demographic factors. Therefore, there is a need for population-specific studies. However, there are no studies in the literature reporting on the features of BRONJ and its treatment in Brazil.This integrative review aimed to determine the clinical profile of osteonecrosis of the jaw exclusively associated with bisphosphonate therapy in the Brazilian population.The guiding question of this review was: What are the clinical features of BRONJ in the Brazilian population that determine its clinical profile?The inclusion criterion for this integrative review was that publications relating to Brazilian individuals would be included: these could include case reports, case series and clinical studies. Over the last decade, the nomenclature, staging and treatment method for BRONJ have undergone changes. This review considered articles either in English or in Portuguese that were published between January 2010 and April 2019. Articles that comprised review of the literature, laboratory analyses, letters to the editor, studies conducted on animal studies and research that did not involve Brazilians were excluded.The variables selected were the following: age, sex, type of bisphosphonate used, duration of use of bisphosphonates until disease manifestation, route of administration, underlying disease that led to indication for drug use, oral region affected by BRONJ, clinical criteria for diagnosis of BRONJ, clinical staging according to the American Association of Oral and Maxillofacial Surgeons (AAOMS),Four online databases were searched for articles: PubMed, Scopus, Web of Science and LILACS. PubMed, Scopus and Web of Science are international databases that have a search filter for the nationality of the articles, and this was used after the initial search. LILACS is a Latin American database with descriptors in the English and Portuguese language. We used the country identification tool for the Scopus, Web of Science and LILACS, and for PubMed we add the descriptor \u201cBrazil\u201d. The descriptors entered in the databases are described below.\u201costeonecrosis\u201d and \u201cbisphosphonate\u201d and \u201cBrazil\u201d for PubMed.\u201costeonecrosis\u201d and \u201cbisphosphonate\u201d for Web of Science and Scopus\u201costeonecrosis\u201d and \u201cbisphosphonate\u201d and \u201cbisphosphonate or \u201cdiphosphonate\u201d and \u201costeonecrosis\u201d for Lilacs.The selection of the articles that were assessed in full for the analysis on each of the variables of this review is described in ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Fifteen studies were included .4,5,9,16,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.The commonest diagnoses relating to BRONJ were: breast cancer, in 60 individuals,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,The types of BPs most related to BRONJ were: zoledronic acid ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Regarding the location of the BRONJ, the mandible was the most affected by BRONJ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,The main diagnostic criterion was clinical evaluation of bone exposure,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,The local trigger factors for BRONJ were the following: tooth extraction,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,According to the AAOMS classification, three individuals (2.12%) presented stage 0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,There was a lack of detailed information about the types of treatment and management used in these cases reported from Brazilian populations. The treatment most reported was sequestrectomy,,,,,,,,,,,,,,,The topical medication most used for treatment of BRONJ was chlorhexidine solution,,The cases of BRONJ in Brazil showed that 103 individuals (80.47%) received BPs intravenously as part of their cancer treatment. The other 25 (19.53%) received BPs orally as osteoporosis treatment. In North American populations, similar results were observed, i.e. BRONJ developed mainly in individuals who were undergoing oncological treatment intravenously.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,The oral route for BPs is more used for controlling osteoporosis: not only in Brazil,,,,,,,,,,,In addition to the type of diagnosis of the disease and type of BP, surgical manipulation of the jawsAmong the triggering factors for BRONJ, implant surgery still remains a matter of controversy in the literature.,,,,,,,,,,,,,,,,,,,,,,,,,,Among the jaw bones, the chance of developing BRONJ is twice as high in the mandible as in the maxilla.,,,,,,,,,,,,,,,,,,,,,,The fact that women have been found to be more affected by BRONJ, both in Brazil and in the rest of the world,Therefore, it is important for medical specialists such as mastologists and/or gynecologists to be aware that patients who use BPs are at greater risk of developing BRONJ. One preventive measure could be to refer patients for dental assessment, before or during the first months of prescription of BPs, in order to eliminate some foci of infection that can expose these patients to the risk of developing BRONJ.,,,,,,,,,,,,This integrative review identified that the majority of the Brazilian cases were diagnosed during stage 2 of BRONJ, and this is similar to findings from other countries.The diagnosis of BRONJ in these Brazilian cases was clinical in all of them. Since 2014, AAOMS has recommended the use of complementary imaging tests to finalize the staging and evaluate possible bone alterations that can precede BRONJ. Despite this recommendation for concomitant use of computed tomography (CT) as the most appropriate examination, the present review identified that only 40.62% of the cases were diagnosed by means of cone beam computed tomography (CBCT). This suggests not only that there is probably a lack of knowledge of indication of 3D imaging such as CBCT to perform better examinations, but also that there is a lack of local resources or else that these examinations have a high cost. The radiographic evaluation criterion was not included in this integrative review because of the lack of detailed information in the studies selected.,,In addition, it is important to mention that, although AAOMS recommends that BRONJ should be diagnosed using clinical and imaging methods, we would emphasize that there is a need to make differential diagnoses in relation to other lesions with clinical signs of bone exposure, such as bone metastases and clinical manifestations of multiple myeloma in the jaw through histopathological analysis.,,The etiology and progression of BRONJ are related to infection and inflammation.,,,,,Among the types of treatment mentioned earlier, surgical treatment is widely used in different populations around the world.The limitation of the present study was its inability to provide detailed information about the location of BRONJ, type and dose of medications, radiographic features, biopsy and follow-up because of the lack of detailed information in the studies selected. In addition, there were no randomized studies or investigations on BRONJ in Brazilian populations. For this reason, we suggest that such studies need to be conducted and need to provide detailed information, as mentioned earlier.The manifestation of BRONJ in this Brazilian population was greatest in the mandibles of younger females, with greater associations with breast cancer and osteoporosis. The major risk factor was previous exodontia, and BRONJ was diagnosed mainly in the intermediate staging (II). Surgical intervention was the treatment most commonly used among these Brazilian patients. This review identified greater use of chlorhexidine solution and prescription of clindamycin as the first-choice antibiotic therapy. PRP was the complementary therapy most used."} +{"text": "In the present study, the influence of spatial confinement on the bond length as well as dipole moment, polarizability and (hyper)polarizabilities of HeH The HeHBerkeley ,4,5. Mortronomy) . All thanomy) [+ ,14,15,16inter alia, an increase of the total energy of the considered chemical object [The main goal of the present work is to analyze the impact of spatial confinement on the geometry and electric properties, i.e., dipole moment, polarizability as well as first and second hyperpolarizability, of HeHpressure . The spapressure ,26,27,28pressure ,20,28. Bl object ,30, sepal object ,32,33, sl object ,35 as wel object ,43,44,45l object and IR fl object . The cyli-th electron. The sum of one-electron contributions, that are described by Equation (N is the number of electrons. By changing the In the present study, the spatial confinement was modelled by the harmonic oscillator potential of cylindrical symmetry: Vconf(r\u2192iVconf(r\u2192iIn all calculations the CCSD method was employed. The geometry of the isolated HeHs et al. The geomr scheme , with thr scheme .R value. Note that we were not able to optimize the HeHThe first step in our study was to analyze how the choice of the basis set affects the bond length of HeH283 a.u. The findThe HeH systems ,51,52,53 systems ,35.In this work, the calculations of electric properties for the spatially restricted HeH reports ,52,53,54 methods ,13. The In summary, in the present study we analyzed the influence of spatial confinement in the form of cylindrically symmetric harmonic oscillator potential, that can be used to model high pressure conditions, on the geometry and electric properties of HeH"} +{"text": "Heavy metals are common environmental contaminants that are toxic, non-biodegradable, and bioaccumulative. They can bioaccumulate through the food chain and present a risk to both public health and ecology. Therefore, this study takes the mangrove wetland of Dongzhai Harbor as an example. The concentrations of heavy metals such as As, Cd, Cr, Cu, Ni, Pb, and Zn in the surface sediments of mangrove wetlands were measured to reveal their distribution, the contamination level was assessed, and the sources of contamination were analyzed. The distribution of Cr, Zn, Ni, Pb, Cu, and Cd concentrations are: Yanfeng East River > Sanjiang River > Yanzhou River > Yanfeng West River, while the As concentration in the Yanfeng West River is greater than that in the Yanfeng East River. According to the correlation analysis, the concentrations of Cr, Zn, Ni, Cu, and Cd are significantly and positively correlated with total organic carbon (TOC), total phosphorus (TP), total nitrogen (TN), and salinity (SAL) and shared a significantly negative correlation with pH. There is moderate contamination risk of As and slight contamination risk of Cd, Cr, Cu, Ni, Pb, and Zn in most regions within the study area. Cd, Cr, Cu, Ni, Pb, and Zn exhibit the same sources, which are mainly influenced by human sources such as aquaculture, agricultural cultivation, and livestock farming, while the source of As comes from aquaculture. Mangroves are widely distributed in the upper intertidal zone of the tropics and subtropics, with high productivity and rapid sedimentation rates . Under tThe fine-grained sediments of mangrove wetlands are rich in organic matter and are prone to accumulating HMs from rivers and tidal waters, which is considered an important \u201cHM sink\u201d . The speHMs have attracted worldwide attention as one of the most serious potential human contaminations in mangrove ecosystems . With thHainan Dongzhai Harbor Mangrove National Nature Reserve is the earliest established mangrove wetland with the most resources and the richest tree species in China . In recegeoI) and potential ecological risk index , total organic carbon (TOC), total phosphorus (TP), and total nitrogen (TN)) and HM elements were analyzed. On this basis, the geo-accumulation index , a drowned valley harbor, located in the northeast of Hainan Island, has the largest continuous mangrove wetland in China . The Zhu2 ,20. The 2 . The ann2 . The annSampling sites were set up to collect surface sediment samples in the mangrove wetlands on both banks of the Yanfeng West River, Yanfeng East River, Sanjiang River, and Yanzhou River in Dongzhai Harbor, with 20 sampling sites from upstream to downstream in each river and a total number of 80 sampling sites. The sampling sites were set up by taking into account topography, hydrological patterns, mangrove density, settlement distribution, and tidal influence. Samples were collected during the summer low tide in August 2020. Each sample was collected from three points near the sample site and mixed, with a soil weight of at least 1 kg. Surface sediments (approximately 0\u201320 cm) were collected using a sediment Peterson grab sampler. Branches, leaves, and other debris were picked out and stored in polyethylene bags. The surrounding environmental conditions were recorded. The sampling apparatus was cleaned before each sampling.The sediment samples were freeze-dried, ground, and passed through 0.25 mm and 0.075 mm sieves, respectively, and then stored at room temperature for backup. The test indexes were as follows: pH, SAL, TOC, TN, TP, As, Cd, Cr, Cu, Ni, Pb, and Zn. The pH, SAL, TOC, TN, and TP tests were done at the School of Environmental Studies, China University of Geosciences (Wuhan). The tests of As, Cd, Cr, Cu, Ni, Pb, and Zn were done at Aoshi Mineral Laboratory, Guangzhou. The dried sediments were extracted at a water-to-soil ratio of 1 to 5, and the pH and SAL of the sediments were measured in the supernatant using a portable water quality multi-reference meter . TOC and3: HCl = 1:3, Analytical Reagent, Charlotte, NC, USA). Next, 10 mL of HF was added, and the reaction was heated in an oven . The solution was then evaporated until nearly dry. After the residual solution was diluted with HF and fixed, Cd, Cr, Cu, Ni, Pb, and Zn were measured by inductively coupled plasma mass spectrometry , while As was determined by atomic fluorescence spectroscopy [The HMs were tested as follows: firstly, 1 g of the sample was weighed into a Teflon tube and then the sample was pre-oxidized with 10 mL of aqua regia (volume ratio HNOgeoI), a method proposed by German scientist Muller in 1969 for studying the quantitative index of the contamination level of each HM in sediments, fully takes into account human contamination, environmental geochemical background concentrations, and factors of natural diagenesis [n in the sedimentary rocks [geoI, the degree of HM contamination was divided into seven levels, as shown in The geo-accumulation index > Cu (0.44) > Ni (0.43) > Cr (0.35) > Zn (0.32) > As (0.21) > Pb (0.19). The value of the coefficient of variation of Cd, Cu, and Ni is larger than 0.36, indicating that their concentrations varied greatly in different areas. Comparing the HM concentrations of the sample with the background values of the Dongzhai Harbor sediments, the concentrations of Cd and Pb were 94% and 109% of the background values, respectively, suggesting that they were less influenced by humans . HoweverAccording to the distribution of different land use types in As shown in The high-concentration areas of Cd are mainly located in the Yanfeng East River and the estuary of the Sanjiang River. Cd is usually derived from phosphate fertilizer and may be released into the sediments through the application of phosphate fertilizer . There aThe concentration of HMs in sediments depends not only on natural transportation and human emissions, but also on a variety of factors, such as the surface patterns of the sediments, organic matter, mineral fraction, and depositional environment of the sediments . The mangeoI of both to be at the no contamination level. As, Ni, Cr, Cu, and Zn are all contaminated to varying degrees, with As showing the highest level of contamination, reaching moderate levels.The results of the geo-accumulation index showed tAs shown in The results of the RI indicate that 40% of the sampling sites were at low risk, while 60% of the sampling sites were at moderate risk. At present, the mangrove wetlands in Dongzhai Harbor are at moderate and low risk. There is no sign of considerable and very high risk. Aquaculture and agriculture as anthropogenic sources of heavy metals can increase HM concentration in sediments ,47. The p = 0 < 0.05) were performed with SPSS 26.0 to indicate that the raw data were suitable for factor analysis [In order to visualize the proximity and similarity among the HMs, a variable clustering analysis was performed on the HMs in the surface sediments . The HMsanalysis . Based oanalysis ,48. The analysis . The estanalysis . In summgeoI and The variance contribution rate of the second principal component (PC2) was 15.43%. Arsenic had a large positive load (0.975). The results of oduction . Therefo(1) The distribution of HMs in the Dongzhai Harbor mangrove wetland is extremely uneven, with the concentrations ranked as follows: Cr > Zn > Ni > Pb > Cu > As > Cd. Among them, the high concentration areas of As are mainly distributed in the Yanfeng West River; the high concentrations areas of Cd are mainly distributed in the Yanfeng East River; the high concentrations areas of Cr, Cu, Pb, Ni, and Zn are mainly distributed in the Yanfeng East River, the upper reaches of the Sanjiang River, the upper reaches of the Yanzhou River, and the estuary of the Yanzhou River. In general, the concentration of HMs in the study area is still at a moderately low level compared with other regions in the world, which may be related to the restriction of Hainan Province on the development of traditional industries that have a serious impact on the ecological environment.(2) The HM concentrations are closely related to the pH, SAL, TOC, TN, and TP of sediments. TOC is significantly positively correlated with Cr, Cd, Ni, Pb, Cu, and Zn. pH is significantly negatively correlated with Cr, Cd, Ni, Pb, Cu, and Zn. SAL is significantly positively correlated with As, Cr, Cd, Ni, Cu, and Zn. TP and TN are positively correlated with Cr, Cd, Ni, Pb, Cu, and Zn.geoI showed that there are As, Ni, Cr, Cu, and Zn contamination of different degrees, while there are no risks of contamination from Cd and Pb. The degree of As contamination is the highest, reaching a moderate level, and the potential ecological risk of As is moderate in 80% of the sampling sites. The potential ecological risk of Cr, Cu, Ni, Pb, and Zn contamination is low. The potential ecological risk of Cd contamination is low at 75% and moderate at 25% of the sampling sites.(3) The results of the (4) The sources of HMs in the sediments of the Dongzhai Harbor mangrove wetland can be divided into two categories. For Cr, Cd, Ni, Pb, Cu, and Zn, they are homogeneous and mainly originate from mixed sources such as aquaculture, agricultural cultivation, and livestock breeding. The source of As mainly comes from aquaculture wastewater, with bait and excrement contributing more to the enrichment of As."} +{"text": "Risk of urinary bladder cancer in patients with inflammatory bowel diseases: A meta-analysis by Geng Z and Geng Q. (2022) Front. Surg. 9: 636791. doi: 10.3389/fsurg.2021.636791A corrigendum on Incorrect AffiliationIn the published article, there was an error in affiliation [1]. Instead of \u201cDepartment of Orthopedics of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China\u201d, it should be \u201cDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Tobacco causes premature death through cardiovascular disease, cancer, and respiratory disease. It has adverse effects on all areas of health, including mental health, with an increased risk of suicide and depression ,2,3,4. TTobacco is a clear, leading preventable cause of death. Reducing tobacco consumption and exposure has become a significant public health priority. The World Health Organization (WHO) enacted the Framework Convention on Tobacco Control (FCTC), the first international treaty in the field of health, in 2003 and is working and cooperating worldwide for tobacco control . FurtherThe most important factor in policy making, including tobacco control policies, is to investigate the current status based on accurate statistics. It is crucial to determine how tobacco-related indices, such as smoking or exposure prevalence, are generated and whether they are accurate. There have been consistent study findings that, although most countries utilize self-reported (SR) data for their official statistics, this does not accurately reflect reality .There are several methods for measuring smoking-related indices, and the most common are SR and biomarkers. SR is the most widely used method to survey populations, owing to its convenience and economic advantage and the ability to examine the indices in various situations and environments. However, tobacco use tends to be underestimated due to social desirability response bias ,10,11. IOne investigation method that is not affected by such bias is the use of biomarkers. Biomarkers are the most accurate indices for tobacco use and smoking exposure . NicotinBiomarkers overcome the subjectivity and inaccuracy of SR, can be used to identify current smokers, and reflect exposure to second-hand smoke in all places. SR-related bias can identify current smokers and individuals exposed to second-hand smoke ,16. MostTherefore, it is not necessarily the case that biomarkers are the best method. Biomarkers are, for instance, more costly than SR; thus, it is not easy to use screening for large-scale surveys. Furthermore, biomarker concentration only shows current smoking or indirect smoking exposure and severity, and cannot shed light on the details of context and situation, such as smoking habits, places, and reasons.Few developed countries, including the United States, United Kingdom, Canada, Korea, and Poland, measure biomarkers in national health surveys ,22,23,24Regarding passive smoking, the United States has already set the reduction of serum cotinine concentration, as opposed to the decrease in smoking on SR, as the target in Healthy People 2030 ,25. The"} +{"text": "Budd\u2013Chiari Syndrome (BCS) is due to thrombosis of hepatic veins (HVs), inferior vena cava (IVC) or both, leading to impaired hepatic venous outflow. Usually, one or more prothrombotic conditions, such as myeloproliferative disorders (MPD), are found. However, a number of cases remain idiopathic ,2,3,4,5.Doppler ultrasound (US) is the main imaging method used to investigate liver dysfunction upon presentation. Historically, Doppler US for BCS diagnosis\u2014the criteria of which is probably in need of refinement\u2014standardized specific signs , suggestive signs , and signs shared with other conditions . HoweverHowever, Doppler US is not always sufficient for BCS diagnosis, and further imaging is recommended (contrast-enhanced CT and/or MRI). However, despite a commendable effort to define the background of a diagnostic approach for BCS, currently, there is no universal standard for diagnosis; some recent proposals, referring to catheter venography and surgery, are debatable . MoreoveHepatocellular carcinoma (HCC) is a challenging diagnosis in the context of BCS. However, generally agreed criteria for HCC diagnosis in cirrhosis cannot apply to BCS. In fact, other benign or intermediate lesions, namely regenerative nodules and adenomas, can appear hypervascular in the arterial phase. Consequently, in the context of BCS, histologic confirmation should be indicated in the work-up of HCC ,20,21,22The main complications of BCS are portal hypertension and development of HCC, though the latter is rare ,4,5,6,7.Overall, previous classifications and prognostic indexes of BCS are of limited value, particularly following the widespread implementation of interventional treatments ,3,4,5,6.Provided that all the indications of BCS management are derived from retrospective studies , followiAnticoagulation is the mainstay of medical therapy, but its efficacy is limited, and it is suitable only for pauci-symptomatic cases. In fact, most cases will eventually require intervention ,2,3,4,5.Technically, TIPS is an intervention that consists of performing, through a trans-jugular access, a shunt between a hepatic vein and a portal vein branch. Initially, this procedure was applied to relief severe consequence of portal hypertension in cirrhosis. In BCS, due to thrombosis extension, TIPS is usually performed through the caval stump. However, its application to BCS has both theoretical and practical advantages. It has symptomatic and therapeutic potential since, particularly in early stages, it can revert liver congestion, the cause of disease progression in BCS. As most the studies suggest, this also allow TIPS to be effective in BCS with severe liver failure, although TIPS would be generally contraindicated in the setting of cirrhosis ,46,47,48Albeit not generally included in guidelines, traditional surgery has a role in BCS management ,53,54,55LT is the last-chance treatment for BCS, once all previous steps have failed, in cases of fulminant liver failure or HCC ,62,63,64The definition for response to therapy is a critical issue and was not stated by AASLD and EASL guidelines ,3,4,5,23However, management and the consequent outcome of BCS are due to these criteria and, according to both a European multi-center published experience and systematic review, about 2/3 of the cases receiving only medical therapy are unlikely to survive long term follow-up ,68,69.Furthermore, early intervention, in the presence of clinical portal hypertension, represents a valid alternative . In factWith regard to the ongoing debate on the timing of BCS treatment, the sustainers of the step-wise management would argue that using such criteria, TIPS for all would be not needed in 30 to 40% of patients who manage well, long term, without it (anticoagulation with or without angioplasty). Hence, they consider the basis for stepwise procedure as a true personalization based on response to treatment. Moreover, postponing TIPS would not impact survival and the To resolve the controversies about timing of BCS treatment, two avenues of research could be taken. The former, and theoretically the simplest, is to directly compare prospectively early interventional treatment versus a step-by-step strategy. However, this trial is unlikely to be performed because it should also involve centers where the step-by-step strategy has been adopted for many years with the aim of questioning the stepwise strategy itself. Moreover, the differences of BCS in the West and in the East represent another limitation.An alternative approach could be to explore which subgroups of patients on only medical therapy would benefit from early intervention ."} +{"text": "Nucleic Acids Research, Volume 32, Issue 18, 15 September 2004, Pages 5553\u20135569, https://doi.org/10.1093/nar/gkh876Following allegations of image manipulation in Figures 1A, 6C, 8B, 8C, and 8E in 2021, the journal conducted a brief investigation, referred the matter to the authors\u2019 institution, and published an Expression of Concern. In May 2022, the institutional panel investigating the allegations concluded the figures are not authentic and the scientific integrity of the article is compromised, and they recommended retracting the article. Their report includes: \u2018On the balance of probabilities, the Panel believe that these data as presented in the publication have been inappropriately manipulated. As such, the data and its interpretation are misleading and unreliable.\u2019 The Editors of the journal are, therefore, now retracting this article."} +{"text": "The blue, green, pink, and red lines indicate the proportion of men and women with the eating disorders listed. This article has been corrected.1In the Research Letter titled \u201cAnalysis of Age, Race, Ethnicity, and Sex of Participants in Clinical Trials Focused on Eating Disorders,\u201d"} +{"text": "Research attention has been drawn to honey\u2019s nutritional status and beneficial properties for human health. This study aimed to provide a bibliometric analysis of honey\u2019s antioxidant and antimicrobial properties. The research advancements within this field from 2001 to 2022 were addressed using the Scopus database, R, and VOSviewer. Of the 383 results, articles (273) and reviews (81) were the most common document types, while the annual growth rate of published manuscripts reached 17.5%. The most relevant topics about honey\u2019s antimicrobial and antioxidant properties were related to the agricultural and biological sciences, biochemistry, and pharmacology. According to a keyword analysis, the most frequent terms in titles, abstracts, and keywords were honey, antimicrobial, antioxidant, bee, propolis, phenolic compounds, wound, antibacterial, anti-inflammatory, and polyphenols. A trend topic analysis showed that the research agenda mainly encompassed antioxidants, pathogens, and anti-infection and chemical agents. In a co-occurrence analysis, antioxidants, anti-infection agents, and chemistry were connected to honey research. The initial research focus of this domain was primarily on honey\u2019s anti-inflammatory and antineoplastic activity, wound healing, and antibacterial agents. The research agenda was enriched in the subsequent years by pathogens, propolis, oxidative stress, and flavonoids. It was possible to pinpoint past trends and ongoing developments and provide a valuable insight into the field of honey research. Honey is a natural product produced by bees. It has been used since ancient times as a food and in various therapeutic applications. It contains several chemical components beneficial to human health, which depend to a large extent on the botanical origin of the plants and the geographical area. Moreover, those two characteristics are used for certification and authenticity. Thus, a significant variability is observed in the physicochemical properties of honey, such as the moisture, pH, free acidity, and electrical conductivity, as well as the content of chemical substances such as organic acids, proteins, amino acids, vitamins, and phenolic compounds. For many years, honey and other beekeeping products such as propolis, pollen, royal jelly, bee venom, and wax have been recognized as bioactive products, with their therapeutic effects extending to a wide range of diseases and infections by pathogens, parasites, and viruses. The action of honey and beekeeping products is mainly due to antioxidant, anti-inflammatory, and immunomodulation factors ,4,5,6,7.Honey research has also extended to more contemporary and complex medical issues. In nutrition science, the consumption of honey and its association with the gut microbiome has recently been studied, since the gut microbiome plays an essential role in chronic diseases. The presence of honey polyphenols may enhance alterations in the balance between pathogenic and beneficial microbial populations in the gut microbiome, providing a beneficial effect .Polyphenols of honey and beekeeping products were also studied for their role in strengthening the human immune system, concerning their contribution to the mitigation of COVID symptoms and the reduction of patient recovery periods. Supplementation of honey with standard pharmaceuticals, such as opinavir/ritonavir tablets, arbidol, chloroquine phosphate, hydroxychloroquineoroseltamivir with or without azithromycin, chloroquine or hydroxychloroquine, or oseltamivir corticosteroids showed promising outcomes in various clinical studies .In addition to polyphenols, honey also contains several carbohydrates, specifically oligosaccharides, and a beneficial role was highlighted in terms of their consumption. Non-digestible oligosaccharides have been studied for their prebiotic effect on the gut microbiome. Specific types of honey may benefit gut microbial populations, offering various nutritional benefits to human health, related to reducing infection and inflammation, as well as obesity, only in animal models ,22.Currently, bibliometric analyses for honey in the Scopus database are rare. By entering the keyword \u201choney\u201d and scanning the database for bibliometric studies, 13 review documents and bibliometric analyses were collected. Six review studies referred to honey, specifically to applications of beekeeping products, their clinical trials and the results of their applications, to bee therapy in general, and the antioxidant properties of beekeeping products in relation to the environment and medicinal plants. The cultural significance of bees in human culture, the presence of chemical contaminants in honey products, and finally, the treatment of diabetic foot ulcers by dressing with honey were also investigated ,26,27,28The existing bibliometric studies, of which only three were conducted using the CSIRO database, investigated various topics around honey and bee products, such as the use of beekeeping products in medicine or the honey itself from 2011 to 2020, honey consumption, and the collapse phenomenon of bee colonies. Likewise, pesticide presence in bee products and honey, the mortality of bees, as well as issues of authenticity and the development of technological methods to determine the origin of honey were studied ,31,32,33The aim of this research was the scientific records of honey\u2019s antimicrobial and antioxidant properties in the Scopus database, from its inception and over the entire available period, as well as mapping of the research frontiers and the research trends in the above topics with modern bibliometric techniques. Additionally, with the help of bibliometric indicators, it is possible to capture the evolution of a scientific object over the years, its research extensions, and the new methods and research protocols it has employed, as well as the revision and integration of further information and fields. Finally, this is the first time that the topic of the antimicrobial activity of honey has become a research theme for bibliometric analysis.The following research questions (R.Q.) offer academics and decision-makers a perspective on the content and topics addressed in the literature. RQ1: What revisions have occurred in the literature on the antimicrobial activities of honey? RQ2: What have been the most influential research articles, authors, and manuscripts from those published in Scopus? RQ3: What are the most important topics discussed in the research field of honey, concerning its antioxidant and antimicrobial properties?This study contributes to the scientific literature, while the bibliometric indexes of this research outline the research production on the antimicrobial and antioxidant properties of honey. Scientific manuscripts cover the period up to the present literature (till 12 November 2022), when research attention on honey and its health benefits was expanded into the nutrition and pharmaceutical domains. Thus, this research aimed to assess the trends and frontiers in the specific health benefits of honey using the Scopus database, various bibliometric indicators, and visualizing the respective scientific literature. An additional goal of this bibliometric study was to reveal the disciplines engaged with honey\u2019s antimicrobial and antioxidant activity, which topics appeared over time, and how they evolved. Moreover, highlighting the primary research streams and presenting the current achievements, ongoing challenges, and trending issues is also accomplished with the aid of bibliometric tools.For the above research, a search was performed in the Scopus database. It includes 1.7 billion cited references and covers nearly 2500 serial titles from approximately 7000 publishers in top-level subject fields: life, social sciences, physical sciences, and health sciences. Additionally, the Scopus database offers many advantages such as diversification, the flexibility of research fields, and an advanced document analyzer mechanism. This mechanism is based on Boolean Syntax for retrieving documents using combining keywords with various Boolean operators ,35,36,37After a preliminary application of various combinations, the phrase \u201cantimicrobial antioxidant honey\u201d was used, with a time range from the initial date of Scopus to 12/11/2022 and with language selection in English, and the following search details: TITLE-ABS-KEY AND OR LIMIT-TO OR LIMIT-TO OR LIMIT-TO OR LIMIT-TO ) AND ). Research documents, reviews, manuscripts from conference proceedings and conference reviews, and book chapters were included.Moreover, the obtained manuscripts were recorded in the Microsoft Excel program by year, subject area, document type, and institutional affiliation. Visual depiction of keywords plus was also realized in this bibliometric research, and specifically, word dynamics and word trends of keywords plus are illustrated. The VOS Viewer program was applied to visualize the results and create a bibliographic map. We performed a co-authorship analysis using the full counting method, assigning the same weight to each co-authorship link. The full counting method was further used in the co-occurrence analysis of the keywords in the manuscript title, abstract, and text. The bibliometric analysis was developed by executing the following steps: research criteria, study questions, and analysis approach selection ; bibliometric data selection and analysis using the bibliometric software; and through generating networks, visualization figures, and interpretation of the results .Research articles (273) and reviews (81) were the most common document types published for \u201cantimicrobial and antioxidant and honey\u201d of the 383 manuscripts .The top ten institutions that published research documents for the abovementioned keywords were also identified. The Universit\u00e0 Politecnicadelle Marche and the King Abdulaziz University were the most productive institutions, followed by the University of Rzesz\u00f3w, the Karadeniz Technical University, and the University of Belgrade-Serbia. Moreover, five European countries, Saudi Arabia, Turkey, Brazil and Thailand, were ranked among the top ten productive research organizations .Considering the top ten productive authors, only Giamieri F had a two-digit number of published documents, namely 11. The number of manuscripts produced by the other authors ranged from five to nine. Battino M. had the best score, with a 70 h-index from the Universit\u00e0 Politecnicadelle Marche, Ancona, Italy. In contrast, Oses, S.M., with a 16 h-index from Universidad de Burgos, Burgos, Spain, was the author with the lowest score. The h-index of the authors is also documented in Two manuscripts appeared in 2001 and are considered the initial efforts to document honey\u2019s antimicrobial and antioxidant properties indexed in the Scopus database. The first research paper highlighThe list of the ten most productive countries includes countries from five continents. Asia had in total of 120 documents, namely: India (32), Turkey (31), Malaysia (30), and Saudi Arabia (27). Italy (28), Poland (28), and Spain (25) represented Europe with 81 records, while Egypt (21) was the only country from Africa. The top ten most productive countries list includes USA and Brazil, with 22 and 26 published manuscripts, respectively. https://www.nationmaster.com/nmx/ranking/honey-production-fao (accessed on 15 January 2023)). In the present bibliometric analysis, some countries lagged behind in honey production even though they were on the list of high research production in absolute numbers of documents, such as Italy, Poland, S. Arabia, and Egypt.The list of the most productive countries in terms of their research performance partially coincided with the most productive countries in terms of honey production. Countries such as Turkey, Brazil, India, and America are in the top ten honey producers, and Spain is in 13th place . Greece, Serbia, and Poland also belong to this cluster. The second cluster (blue color) includes three countries, Turkey, Iran, and Italy. The green cluster encompasses more countries, namely, eight: Australia, Malaysia, Pakistan, Egypt, USA, India, Saudi Arabia, and China. The purple cluster has three countries, Spain, Italy, and Ecuador. Only one country, Argentina, exists in the fifth cluster (orange).https://www.scimagojr.com/comparecountries.php?ids=sa&ids=eg&ids=pt&ids=br&ids=it (accessed on 15 January 2023)).Notably, the above five countries dedicated significant research efforts to chemistry and life sciences from October 2021 to September 2022, as indicated in the index produced by Nature about the collaboration of countries. In accordance with the Scimago Journal & Country Rank regarding the country comparison, it was appropriate to consider additional metrics for collaboration and international research initiatives stemming from these countries. Thus, Italy had the biggest h-index 1.2 k, followed by Brazil (h index 690), Portugal (h-index 559), Saudi Arabia (h-index 478), and Egypt 349(h-index). Regarding the percentage international collaboration, in the last two years, Saudi Arabia was the leading country, followed by Egypt, Portugal, Italy, and Brazil. Since 2009 all these countries have increased their collaboration networks and international research streams ; biochemistry, genetics, and molecular biology (13.7%); pharmacology, toxicology, and pharmaceutics (12.9%); and medicine (12.4%). Furthermore, as shown in Molecules (15), Antibiotics (12), Lwt (12), Food Chemistry (10), and Foods (10). The list of the most relevant journals included the Journal of Agricultural Research (10), Applied Sciences (6), Evidence Based Complementary and Alternative Medicine (6), Food and Chemical Toxicology (6), and Food Research International (6).Considering the relevant sources, the scientific journals that published a double-digit number of articles included Evidence-based Complementary and Alternative Medicine, and the highest was 13.1 (2021) for the journal Food Chemistry. The many research areas of these sources include organic chemistry, medicinal chemistry, natural products, natural antibiotics, bee management, and advances in research into antibiotics and related bioactive therapeutic agents.The above scientific journals have a high scientific impact and cover various multidisciplinary research topics. In particular, the lowest citation score was 3.2 (2021) for the Journal of the American College of Nutrition [The top ten most cited articles referring to the antimicrobial and antioxidant properties of honey are listed in utrition . It is wThe most cited document addressed honey\u2019s composition and nutritional contribution, while the second highest discussed the antioxidant and antimicrobial activities when utilizing reactive oxygen species . The thiContinuing with the other most influential documents, we identified manuscripts that focused on correlating the botanical origin of honey with characteristics such as its color, total phenolic, flavonoid, ascorbic acid, amino acid, protein, and carotenoid contents. Honey\u2019s antimicrobial capacity was also tested against Gram-positive and -negative bacteria, showing miscellaneous sensitivity results. The correlation between the chemical components of honey, such as phenolic content and hydrogen peroxide, influenced the general antimicrobial activity of the honeys, as documented in the following article from the list presented in The following article presented an extensive literature review of the beneficial properties of honey in human health and recorded, in addition to its known antimicrobial and antioxidant properties, beneficial effects on cardiovascular function, the respiratory system, the fight against cancerous tumors, and the fight against diabetes . SubsequIn the present bibliometric analysis, four articles also used a questionnaire. The first survey investigated the acceptance of an innovative product consisting of honey and propolis among 69 consumers. The content of the above product with honey and propolis at 0.5% was characterized as unpleasantly resinous and bitter. Finally, the composition at rates of 0.5% and 0.3% of propolis were chosen as suitable potential combinations for commercial exploitation . A similSubsequently, when two manuscripts cite a third, they have a relationship and should be grouped in a visualization map. The bigger the node size (author), the more productive the author. The distance between the nodes in the visualizing network is proportional to their subject-relatedness. Node distance in the network map represents their subject relatedness. The thickness of the lines between the network nodes illustrates the bibliographic coupling strength between the authors .Author\u2019s scientific links and international collaboration have mutual benefits for the productivity of the authors, for the global impact of their institutions, and for the scientific standing of the countries. Thus, international authorship and diversification of affiliations in research papers can elevate authors\u2019 scientific impact and increase their publishing activity and prestige .The minimum number of manuscripts per author was set as four. Therefore, only 16 of 1730 authors were considered for inclusion in the visualization network. In particular, three clusters are shown, the blue with three authors (cluster 3), the red with seven authors (cluster 1), and the green with six authors (cluster 2). The respective number of documents for each group was 13, 34, and 43. Os\u00e9s, Sandra M was the leading author for total link strength (2606) in the red cluster. His research focused on honey, botany, stingless bees, spray drying, and drug formulation ,66. GiamThe following figure correspoThe above word clouds show that the most frequent keywords occurred more than ten times in titles, abstracts, and keywords. There was a high level of similarity among the most frequent words: honey, antimicrobial, antioxidant, bee, propolis, and phenolic compounds. \u201cPollen\u201d, \u201cwound\u201d, \u201cantibacterial\u201d, \u201canti-inflammatory\u201d, \u201cchemical\u201d, \u201cpolyphenols\u201d, and \u201cmanuka honey\u201d were also words that appeared in the collected manuscripts. As expected, the search keywords antimicrobial, antioxidant, honey; the respective stemming terms; and their derivatives prevailed in the word clouds.E. coli, Clostridioides difficile strains, and Mycobacterium abscessus [Research into the properties of manuka honey began in the early 90s and has continued ever since. Studies on the beneficial properties of this honey have expanded in many areas of medicine, pharmacology, and immunology. In addition, the antimicrobial activity of manuka honey and its mechanism of action have been investigated against various pathogens, such as bscessus ,72,73,74In the following figures, word dynamics and trends of Keywords plus are depicted. Keywords plus are produced automatically and include words or phrases derived from an article\u2019s citation list, yet they do not necessarily exist in the title. Furthermore, Keywords plus provide a detailed picture of a manuscript\u2019s scientific content and research depth, and their implementation in bibliometric analysis has become popular .Staphylococcus aureus, Eschericia coli, and anti-infective agent\u201d.The dynamics of ten keywords since 2001 are represented in Escherichia coli) and Gram-positive coccus (Staphylococcus aureus), which also shows the research diversity recorded concerning pathogenic microorganisms [The term with the most significant dynamic and an escalating upward trend in terms of its use was \u201choney\u201d, which was also a search term. In the year 2001, it appeared three times, and in the year 2022, it occurred 291 times. For the rest of the terms, it is noticeable that until the year 2009, they all had single-digit appearance numbers, while recent years ranged from 87 (anti-infective agent) to 133 (non-human). The dynamics of terms related to honey\u2019s microbial and antioxidant properties also showed a significant increase in their usage. In addition, the dynamics of terms referring to microorganisms were also shown to be escalating. It is also noteworthy that among the most dynamic terms were Gram-negative bacillus , anti-infective, and chemical agents, as well as on propolis [Selecting keywords plus one can reveal the main topics and research trends. As a result of the trend topic analysis, it was observed that the research on honey\u2019s antimicrobial and antioxidant activity mainly concentrated on antioxidants, pathogens , color, polyphenols concentration and identification, flower properties, and origin, as well as antibacterial agents such as gentamicin and chitosan ,84,85,86The map categorizes terms into two significant clusters, with respective colors. The color of an item is determined by the cluster to which it belongs. Moreover, the closer two items are located on the map, the stronger their relatedness. Based on the network map, two clusters were identified. The terms with the highest occurrence from the first cluster were antioxidant activity, antimicrobial activity, antioxidant, nonhuman, human, and controlled study. Similarly, the terms from the second cluster were honey, antioxidant, anti-infective agent, chemistry, and phenol derivative. An analytical description of the correspondence terms is presented in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Moreover, this cluster includes additional terms such as chemical composition, radical scavenging assay, natural product, propolis, polyphenol, antineoplastic activity, plant extract, physical chemistry, oxidative stress, and HPLC. The research topics of honey, wound healing, and antineoplastic activity are also found in this cluster.The red cluster contains 34 keywords and their co-occurrence relationships. This cluster delimits the research frontiers of honey\u2019s antimicrobial, antifungal, and antioxidant properties. It contains terms such as controlled study, minimum inhibitory concentration, hydrogen peroxide, quercetin, ascorbic acid, gallic acid, and enzyme activity, as well as three pathogenic microorganisms of significant importance: The green cluster includes 21 keywords and mainly refers to honey\u2019s chemistry and chemical compounds. Chemistry, phenol derivative, food products, animals, phenols, anti-bacterial agents, flavonoids, drug effect, phenolic compounds, polyphenols, pollen, microbial sensitivity test, and anti-inflammatory agent are keywords residing in this cluster. The second cluster covers the main anti-ineffective, antimicrobial, anti-bacterial, and anti-inflammatory issues. This cluster provides research approaches to anti-bacterial and anti-inflammatory agents and considers the relationship between honey and the mode of action of chemical compounds. 2O2) content significantly influences its antimicrobial activity. In addition to H2O2, methylglyoxal (MGO) also affects honey\u2019s antimicrobial activity. In manuka honey, MGO ranges from 38 mg/kg to 761 mg/kg, which is, comparatively, up to 100-times higher than most common types of honey [Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium, and Enterococcus faecalis [Methodical and extensive research has been carried out into the properties of manuka honey. Its proven utility in antimicrobial and therapeutic applications has made it a valuable solution to various medical problems. The superiority of manuka honey lies in its wide variety of flavonoids and multiple chemical compounds, which increase its therapeutic effect . Honey\u2019sof honey . The antfaecalis ,88,89.Manuka honey has also been studied regarding wound healing and tissue regeneration. In addition to its antimicrobial action, it prevents the formation of microbial biofilms and reduces the infected area. Its action in tissue healing and renewal is based on reducing inflammatory cell response and, concurrently, activating cytokine production in the wound area, resulting in the proliferation of epithelial cells. On this basis, various formulations based on honey, and in combination with other substances such as hyaluronic acid and zein coatings, have been tested ,91,92,93Candida albicans\u201d [The antimicrobial activity of honey and its research significance was established by the corresponding keywords found in both clusters, highlighted by the bibliometric analysis. Additionally, in the red cluster, there are indications for honey research regarding its antifungal activity: \u201cantifungal activity, lbicans\u201d ,94. Morelbicans\u201d ,97,98,99The presence of the terms \u201chigh-performance liquid chromatography, in vitro study\u2019\u2019 in the red cluster refer to various technological research aspects. The link between the beneficial properties of honey and beekeeping products focuses on characterizing these antimicrobial and antioxidant substances. Methodological approaches using specific instruments, such as liquid chromatography, are recorded in the literature. Such studies emphasized the determination of the chemical components of antimicrobial and antifungal activity, the identification and authentication of honey varieties, and the determination of the geographical origin and the corresponding chemical profile ,106,107.The terms \u201cquercetin, ascorbic acid, and gallic acid\u201d, appearing in the same cluster as the term HPLC, are chemical substances used as standards for determining bioactive compounds such as total phenolic content, phenolic compounds, antioxidant activity, vitamin C, and sugars. Together with the other terms that appear in both clusters , they depict the research output determining the phenolics and flavonoids in honey, as an essential component of the verification of their antimicrobial and antioxidant activity ,112,113.In-depth research has also been conducted on other beekeeping products, such as propolis. This natural product has attracted the attention of scientists for decades because of its chemical composition, which offers many therapeutic utilizations and a multitude of pharmacological applications. Propolis chemical synthesis is commonly composed of 50% resin, 30% wax, 10% essential oils, 5% pollen, and 5% other substances, which include organic compounds and minerals such as phenolic acids (cinnamic and caffeic acid) or their esters, terpenes, flavonoids , aromatic aldehydes, alcohols, and fatty acids among others. Propolis\u2019 chemical composition is related to the geographical, botanical, and environmental conditions of the region of harvest ,115,116.Salmonella enterica, Yersinia enterocolitica, Staphylococcus aureus, and Listeria monocytogenes; Propionibacterium acnes; and the fungi Candida albicans and Saccharomyces cerevisiae [Propolis has been studied in combination with honey and other substances, such as nanomaterials, to restore, regenerate, and heal skin damage and burn wounds. It has also been analyzed for its use as a bio preservative and food additive, as well as for its antimicrobial and antioxidant properties against pathogenic microbes and fungi such as revisiae ,120,121.In the second cluster, the green one, the keywords \u201cbee\u201d and \u201cpollen\u201d also appear. They are related to honey research and beekeeping. The stingless bee and its products, honey, propolis, and pollen, have attracted particular attention in the beekeeping research community. These products are being studied for their beneficial effects, not only from a medicinal point of view, but also from a nutritional point of view, with foods containing stingless bee honey being considered a super-food ,123.Pollen is also highlighted in the green cluster. Processed pollen, which acts as a nutritional source for honey bees, is called bee bread. This honey product is a potential functional food with research initiatives identifying over 300 bioactive molecules from various geographical areas worldwide, such as free amino acids, fatty acids, minerals, vitamins, organic acids, and polyphenols ,124. ResA visualization of the selected keywords and the evolution of research using the total link strength of VOS viewer is shown in Identifying potential therapeutic compounds in honey and the antioxidant background are topics that emerged in the scientific community. The use of honey as a therapeutic agent for various diseases and its role in controlling disease conditions have gained attention. Research papers revealing honey\u2019s mode of action based on flavonoid and polyphenol substances and the antimicrobial spectrum were also produced by various authors. Honey and honey product investigation emphasized the antitumor activity and anti-inflammatory capacity of propolis and the positive biological effects in medicine and the cosmetic industry ,132,133.E. coli, S. aureus, propolis, phenolic compounds, oxidative stress, and flavonoids. Research issues concerning anti-infection and anti-inflammatory agents were also highlighted. At the same time, pollen and free radical scavenging also entered the scientific domain of the antimicrobial and antioxidant usage of honey.In the subsequent years, the research agenda was enriched by Scientific works have already demonstrated the antimicrobial status of propolis and the combination of propolis with honey. Moreover, pollen was investigated in various clinical projects, probing its radio-protective, anti-chemo toxicity, and nutrition potential. Research concerning propolis mainly concentrated on botanical origin, flavonoid content, and antibacterial effectiveness, due to cytoplasmic membrane function modification, inhibition of biofilm formation, and cell membrane proteins. Scientific studies have already demonstrated the antimicrobial status of propolis and the combination of propolis with honey. Moreover, pollen was investigated in various clinical projects probing the radio-protective, anti-chemo toxicity and nutrition potential. Research concerning propolis mainly circulated to the botanical origin, flavonoid content and antibacterial effectiveness due to cytoplasmic membrane function modification, inhibition of biofilm formation and cell membrane proteins ,134,135.2O2 and oxidative stress significantly damages DNA, RNA, and cell permeability [Bacterial antimicrobial resistance to pathogens was another topic that emerged in the literature regarding the clinical aspects of honey and its derivative products. The role of reactive oxygen species (ROS) in antimicrobial resistance was also highlighted. ROS in the form of Heability .E. coli and S. aureus were conducted between 2018 and 2020. In this regard, the antibacterial activity of honey against methicillin-resistant (MRSA) S. aureus isolated from patients with diabetic foot ulcers was recorded in 2020. The authors concluded that honey could be efficiently used for diabetic foot ulcer treatment, to combat S. aureus infection. Honey type is a crucial factor determining the levels of phenolic and flavonoid compounds and, thus, different antibacterial behaviors. In dark forest honey and honeydew honey, these compounds performed successfully against Gram-positive and Gram-negative bacteria [In addition, antibacterial tests with honey against significant pathogens such as bacteria ,140,141.Furthermore, the biological activity and the role of gallic acid and quercetin entered the field at the end of the last decade, along with the bioactive properties of antioxidants, and new determination and identification methodologies. Determination of phenolic compounds using high-performance liquid chromatography (HPLC) utilizes gallic acid, caffeic acid, syringe acid, chlorogenic acid, p-coumaric acid, ferulic acid, catechin, quercetin, and chrysin, among others.These compounds characterize the color, sensory profile, and therapeutic properties of honey. Total phenolic acid and flavonoid content, hydrogen peroxide removal activity, the effect of removal of DPPH radicals, total antioxidant capacity, and measurement of reduction potential are representative methods applied in honey research, to emphasize its nutritional and health-beneficial activities. Concerning the physicochemical properties of honey, specific emphasis was given to color, water and moisture content, organic acids, acidity and pH, electrical conductivity, and ash content ,141,142.Honey and honey products are of great importance in terms of their nutritional and therapeutic properties, as well as the health implications for the hygiene status of humans. Various research projects and initiatives have focused on the antimicrobial and antioxidant profiles of various types of honey. Honey is in the spotlight of worldwide research activity, and this activity has expanded beyond the botanical origin of honey and its products. Honey research encompasses clinical studies and multiple pharmacological perspectives.This bibliographic analysis revealed the antimicrobial and antioxidant attributes of honey explored since 2001. Three-hundred-eighty-three manuscripts met the search criteria in the Scopus database. The most retrieved manuscripts belonged to the agricultural and biological sciences, biochemistry, genetics and molecular biology, pharmacology, toxicology, pharmaceutics and medicine. The list of the ten most productive countries included countries from five continents. Asia had a total of 120 documents, namely: India (32), Turkey (31), Malaysia (30), and Saudi Arabia (27). Italy (28), Poland (28), and Spain (25) represented Europe with 81 records, while Egypt (21) was the only country from Africa.Subsequently, this bibliometric study allowed visualization of the research trends regarding honey\u2019s antioxidant and antimicrobial properties over the last 22 years. The co-occurrence analysis of keywords revealed that research topics such as propolis, flavonoid, anti-inflammatory activity, wound healing, chemical composition, polyphenol, antineoplastic activity, manuka honey, antifungal activity, phenolic compounds, and pollen were highly related to the antimicrobial and antioxidant characteristics of honey.E. coli and S. aureus, and the mode of action of propolis, phenolic compounds, oxidative stress, and flavonoids.The initial research focus in this domain was primarily on honey\u2019s anti-inflammatory and antineoplastic activity, wound healing, and antibacterial agents. In the following years, the research agenda was enriched by studies concerning the use of honey and honey products against pathogens such as Possible limitations of this research might be the single database utilized, the language, the document types, and the selection of specific bibliometric indicators. Despite these limitations, this study provides a significant global output regarding honey research and trends. Overall, there is still a need to understand the mode of action of all antimicrobial and antioxidant agents of honey and honey products, as well as to further investigate all of their potential therapeutic options."} +{"text": "Since the beginning of the COVID-19 pandemic, a great variability of symptoms that affect all organs and systems of the body has been identified in patients with SARS-CoV-2 infection; this symptomatology can sometimes persist over time, giving rise to the so-called long COVID or post-COVID. The aim of this study is to delve into the clinical characterization of these patients, as well as to take into account the influence of factors such as hospitalization, admission to ICU, history of pneumonia, or vaccination status on the persistence of symptoms.ad hoc questionnaire, and statistical analysis was performed using SPSS Software Version 25 .An observational, descriptive, multicenter, and retrospective study was designed with a series of cases of people who presented long COVID, which includes univariate, bivariate, and multivariate analyses. Data were obtained from an online Hospitalization, ICU admission, history of pneumonia, and vaccination were predictive factors (positive or negative) for the following long-COVID symptoms: headache, menstrual disorders, joint pain, cough, chills, nasal congestion, back pain, abdominal pain, weight loss, eye discomfort, facial erythema, itching, tremors, dizziness, seizures, sleeping difficulty, dry eyes, palpitations, fatigue, paresthesia, dyspnea, aphonia, chest pain, high blood pressure, vomiting, memory loss, brain fog, hypothermia, low blood pressure, sputum or phlegm, lack of concentration, hair loss, and erectile dysfunction.This study provides evidence on the clinical characterization of patients suffering from long COVID in order to offer them the most appropriate treatments. The SARS-CoV-2 infection presents associated symptomatology of great interest to public health due to both the transmission and the appearance of new variants rapidly on all continents. The COVID-19 disease manifests itself in various ways; it can be asymptomatic, mild, moderate, or severe .A variety of Spanish studies , 5, as wThe prevalence of persistent COVID-19 is around 10%, although it ranges between 10 and 36% depending on the sociodemographic and clinical characteristics of the study population . A studyInitially, the WHO identified 33 symptoms of long COVID althoughSince the appearance of the first cases of infection by the SARS-CoV-2 virus, new data on its clinical and epidemiological characteristics have been incorporated; however, there is less scientific evidence that addresses how certain characteristics such as hospital admission, history of pneumonia, or vaccination can influence the appearance of different symptoms from the clinical and epidemiological point of view of persistent COVID-19.The available evidence on COVID-19 is mainly focused on hospitalized cohorts \u201324 that The WHO and the Long Covid Forum Group established a research priority on long COVID to improve the clinical characterization of these patients to offer them appropriate treatments . Crook eTherefore, considering all of the abovementioned points, this study aimed to analyze whether hospital admission, ICU admission, history of pneumonia, and vaccination can be predictor factors for the different symptoms of persistent COVID-19 or long COVID.An observational, descriptive, multicenter, and retrospective study was designed with a series of cases of people who presented long COVID or post-COVID syndrome, understanding that the \u201ccondition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis\u201d . The stuThe study included patients from the general adult population who attended the Spanish National Health System with the following selection criteria: (a) Should be a resident of Spain and have an age \u226514 years, (b) should meet the clinical-epidemiological criteria of the long COVID-19 disease, and (c) should consent to participate in the research study.https://www.imim.es/ofertadeserveis/software-public/granmo/).As for sample size, there is less knowledge about the actual prevalence of long COVID-19. Assuming a long COVID-19 prevalence of 10.0% , a samplThe research project obtained the authorization of the Direction/Management of the C\u00f3rdoba and Guadalquivir Primary Care Health District and the South Health Area of C\u00f3rdoba, as well as the approval of the Clinical Research Ethics Committee of the Reina Sof\u00eda Hospital in C\u00f3rdoba (reference: 5033). Informed consent was requested as part of the online questionnaire, which gives voluntariness to the study patients. The processing of the data was in accordance with the provisions of the European Data Protection Regulation and Organic Law 3/2018 on the Protection of Personal Data and the guarantee of digital rights.https://docs.google.com/forms/d/e/1FAIpQLSeO2odLrsCGf_aA6PbRbAziMA3ZP43wAmo81rRgKuLmmnaXCg/viewform), which was forwarded to the partners of the persistent COVID associations existing in Spain. The questionnaire was designed and approved by members of the Multiprofessional Teaching Unit of Family and Community Care of the C\u00f3rdoba and Guadalquivir Health District, with proven experience in the design and validation of surveys. The questionnaire was subjected to a process of consensus, apparent logic, and content validation .The information about the participating patients was obtained from an online questionnaire , as well as the following personal health history, namely, the vaccination status for COVID-19 and symptoms presented in patients with long COVID-19, was collected. Hospital and intensive care unit (ICU) admissions, as well as history of pneumonia, were taken into consideration as background. Regarding the long COVID-19 symptoms, a list of 56 possible symptoms was taken into account for the situation of persistent COVID-19: sore throat, headache, joint pain, muscle pain, unusual tiredness or fatigue, breathing difficulty, lack or loss of smell, lack or loss of taste, cough, dyspnea, fever, sweating, chills or shivering, nasal congestion, aphonia or hoarseness, malaise, chest pain, back pain, chest tightness, diarrhea, stomach pain, abdominal pain, vomiting, nausea, loss of appetite, weight loss, hypothermia, eye discomfort , facial erythema, limbs pseudo freezing , sputum or phlegm , hemoptysis (bloody sputum), swelling or inflammation of the fingers, itching (pruritus), hives or eczema on the skin (rashes), tremors, dizziness, seizures, memory loss, mental confusion, sleeping difficulty, lack of concentration/attention deficit, mental fog, post-traumatic stress, paresthesia, swallowing difficulty, ear beeps or tinnitus, dry eyes, conjunctivitis, palpitations, high blood pressure, low blood pressure, hair loss, erectile dysfunction (men), and menstrual disorders (women).The participants were asked to fill in the online questionnaire on Google Drive. Later, the responses were exported to an Excel sheet from Google Drive and statistically treated with the SPSS Software Version 25 .First, a descriptive analysis of the studied variables was performed using frequencies and percentages when they were qualitative or categorical variables and measures of central tendency, dispersion, and position when they were quantitative variables. We estimated confidence intervals for 95% (95% CI) for safety of the main parameters.Next, a bivariate analysis (chi-square test) was performed, considering the exact bilateral significance (Fisher's exact test) as there are 2 \u00d7 2 tables in all cases, to determine if there was any relationship between each of the 56 persistent symptoms of long COVID and hospital admissions or vaccinations. Once the significant relationships were defined, an analysis of the magnitude of the effect of the association was also performed, calculating the odds ratio to determine if the variables were predictors for the symptoms with which they had previously demonstrated a relationship. For this analysis, an OR < 1.68 is considered to be of negligible magnitude, an OR between 1.68 and 3.47 was considered small, an OR between 3.47 and 6.71 was considered moderate, and an OR > 6.71 was considered large , so magnp-value, and RO = e[\u03b2i* (\u00b1\u0394i)] adjusted with their 95% confidence interval limits. For the analysis of statistical significance, a p-value < 0.05 was established. The goodness-of-fit of the model was analyzed using the Hosmer-Lemeshow test.Finally, once determined by the previous bivariate analysis, the variables were presumably related in a bivariate way to hospital admissions or vaccinations, and to establish a predictive model that included the factors that had shown the predictive capacity for the symptoms of long COVID, a binary logistic regression analysis was performed to be able to control the predictor and/or confounding factors. The dependent variables were each of the symptoms with more than one predictive factor, and the independent variables were each of those factors to obtain the coefficient \u03b2, the statistician \u03c72 Wald, The total number of participants with long COVID was 681. The mean age was 45.78\u00b19.65 (SD), ranging from 14 to 76 years (mean 95% CI: 46.02\u201346.46). Of 681 participants, women made up 83.1%; 79.3% resided in urban areas ; and 41.0% were on sick leave from work due to persistent COVID-19. Of the total patients, 23.3% were hospitalized, with 3.5% in an ICU, 29.8% presenting pneumonia after the diagnosis of COVID-19, and 87.4% being vaccinated against COVID-19.To find out if the variables hospitalization, ICU admission, and history of pneumonia were related to each of the persistent symptoms of long COVID, a chi-square test was performed. The significant results obtained in these analyses are shown in 2 < 0.001).This last step of logistic regression has excluded hospitalization for the lack of concentration and low blood pressure and history of pneumonia for erectile dysfunction from the explanatory models. In the case of mental confusion and hair loss, the Hosmer-Lemeshow test indicates that this model has not got an appropriate fit for headache, menstrual disorders, joint pain, cough, chills, nasal congestion, back pain, abdominal pain, weight loss, eye discomfort, facial erythema, itching, tremors, dizziness, seizures, sleeping difficulty, dry eyes, palpitations, fatigue, paresthesia, dyspnea, aphonia, chest pain and high blood pressure, vomiting, memory loss, brain fog, hypothermia, low blood pressure, sputum or phlegm, lack of concentration, hair loss, and erectile dysfunction. Nowadays, there is less evidence that focuses on the predictive factors for each of the symptoms. However, some investigations determined that patients who required hospitalization present a significant proportion of late clinical events and persistent symptoms in the medium-term (2 months) and the long-term (6 months) .Fernandez-de-las-Pe\u00f1as et al. found that a higher symptom burden in the acute phase of COVID-19 infection and a higher number of preexisting medical comorbidities may predict a higher likelihood of persistent COVID symptoms, particularly fatigue or dyspnea 3\u20136 months later. These factors are also mentioned in other recent studies, suggesting that post-COVID symptoms are more prevalent in patients with severe symptoms at the onset of infection and in hospitalized patients , 28, 29,Our results showed that hospitalization is a risk factor for fatigue and paresthesia , as well as dyspnea, aphonia, chest pain, and high blood pressure. One study compared post-COVID-19 fatigue with chronic fatigue syndrome as there are overlaps between them; however, although fatigue is shown to be an important symptom of long COVID, research showed that there is no relationship between COVID-19 severity and long-term fatigue . In addiRegarding the symptoms of patients who required ICU admission, ICU admission itself proved to be a protective factor for headache, menstrual disorders, and hair loss (as well as being vaccinated for the latter); however, it became a risk factor for erectile dysfunction, along with those who were hospitalized. Garrigues et al. analyzed 120 patients and identified that the most common persistent symptoms in a sample of hospitalized people, at 110 days on average after admission, were fatigue (55%), dyspnea (42%), memory loss (34%), concentration disorders (28%), and sleep disturbances (30.8%). In contrast, there was no difference between \u201cstandard patients\u201d and those who needed ICU during their hospitalization for thesFurthermore, studies showed that physical, cognitive, and mental deterioration, which persists long after the acute COVID-19 disease, is common in ICU survivors and thatHowever, vaccination is a protective factor for other symptoms such as joint pain, cough, chills, nasal congestion, back pain, abdominal pain, weight loss, eye discomfort, facial erythema, itching, tremors, dizziness, convulsions, difficulty sleeping, dry eyes, and palpitations. Some studies pointed in the same direction as ours, so vaccination is useful for improving symptoms in people who already have the disease \u201339. ManyIn addition, vaccines are an important preventive strategy for long COVID , 42, as The explanation of symptoms with more than one predictor is based on logistic regression analysis, except for mental confusion and hair loss, where it is based on OR, as the logistic regression model does not fit adequately.As for limitations, it is important to note that the type of survey used may introduce a kind of selection bias. In addition, there is also a possible information bias as the information came from the patient himself and was not contrasted or confirmed by a physician, so the results should be taken into account with caution. Furthermore, although there is evidence on the predictors of long COVID as a whole, the evidence on the predictors of each of the symptoms is very scarce, so in this part, there has been a limitation in contrasting the results obtained with other similar studies; however, the scarcity of similar studies is a strong point to be taken into account in this research and it is advisable to continue to deepen this line of research. This research is presented as a case series study without a control group, which implies a methodological limitation that could compromise its validity. Therefore, the results obtained must be taken into account together with the limitations of the type of study design, and further research is needed to contrast the results offered. Another limitation of this study is the lack of temporality of the COVID-19 infection and the administration of the COVID-19 vaccine. Future studies should evaluate the chronological association between both variables.In conclusion, hospital admission, ICU admission, history of pneumonia, and vaccination are predictors of some of the symptoms of persistent COVID-19 or long COVID. This provides evidence for the priority set by the WHO and the Long Covid Forum Group to improve the clinical characterization of patients suffering from long COVID in order to offer them the most appropriate treatments. Therefore, this study contributes to identifying predictors of the different symptoms that may appear in the course of long COVID, which is important to be able to develop preventive and symptomatic treatments early and to plan recovery interventions.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Comit\u00e9 de \u00c9tica en Investigaci\u00f3n Cl\u00ednica Hospital Reina Sof\u00eda, C\u00f3rdoba, Spain. The patients/participants provided their written informed consent to participate in this study.ER-R, LP-dT, RC-J, JG-L, CJ-G, JG-B, JG-S, RV-S, ES-G, and MS-P were involved in the conception and design of the study, as well as the data acquisition. JG-B and MS-P performed the analyses. ER-R, MS-P, and LP-dT drafted the manuscript, which was revised by JG-S, RV-S, and ES-G. All authors listed have made a substantial, direct, and intellectual contribution to the study and have approved it for publication.This research was funded by the call for research and innovation projects in the field of primary care, regional hospitals, and high-resolution hospital centers of the Public Health System of Andalusia in 2021 by the Progreso y Salud Foundation of the Ministry of Health and Families of the Junta de Andaluc\u00eda, with EXP. No. AP-0184-2021- C2-F2.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The authors wish to update the following statements in their original Article:Funding was provided by Glenmark Pharmaceuticals. Study medication was provided by SaNOtize. Glenmark Pharmaceuticals and SaNOtize played a role in study design, data collection and analysis, and interpretation; in the writing of the manuscript; and in the decision to submit the paper for publication.Individual participant data are not available publicly. De-identified individual participant data can be shared on receipt of reasonable request .MT, WW, RK, AP and SR are employees of Glenmark Pharmaceuticals Limited. MT is Senior Vice President at Glenmark. KM is employee of and CM is Co-Founder & Chief Scientific Officer at SaNOtize Research & Development Corp. SJ has been a speaker for Abbott, Alkem, AstraZeneca, Micro, Boeringher Ingelheim, Novo Nordisk, MSD, Sanofi, PHFI, Lupin, Eli Lilly, Bayer Zydus, Zydus Cadila and DRL; and on advisory board for Abbott, Glenmark, Biocon, Zydus Cadila, Bayer Zydus Twin Health, Marico, Franco India, Cipla, Sun, Torrent and USV. Y-PT has received investigator-initiated research grant and payment for presentations from Abbott. SW does not have any competing interests to declare."} +{"text": "In the published article, there was an error in affiliation 7. Instead of \u201cDepartment of Chemistry, Faculty of Science, Research Centre for Modelling and Computational Sciences, Ferdowsi University of Mashhad, Mashhad, Iran\u201d, it should be \u201cDepartment of Physics, Kazan Federal University, Kazan, Russia\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in affiliation 1.Instead of \u201cInstitute of Hydraulic Engineering and Water Resources Management, Vienna, Austria,\u201d it should be \u201cInstitute of Hydraulic Engineering and Water Resources Management, TU Wien, Vienna, Austria.\u201dIn the published article, there was an error in affiliation 2.Instead of \u201cResearch Group Environmental Microbiology and Molecular Diagnostics E166/5/3, Institute of Chemical, Environmental and Bioscience Engineering, Vienna, Austria,\u201d it should be \u201cResearch Group Environmental Microbiology and Molecular Diagnostics E166/5/3, Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, Vienna, Austria.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "An inventory of herpetofauna species from western part of Nusa Kambangan Island, Central Java, Indonesia, is presented. There are 43 herpetofauna species reported (16 amphibians and 27 reptiles). This study confirmed new distribution record and list some of threatened species. In light of the imminent human disturbances on Nusa Kambangan Island, a conservation plan is urgently needed. The first comprehensive survey of Nusa Kambangan Island\u2019s herpetofauna from the west part.The confirmation and distribution record of a several herpetofauna species are reported.Lowland forest type 1 became the most significant habitat due to its high species richness of herpetofauna, but it was threatened by human disturbance.Cyrtodactylus and is considered an ecologically significant area due to its diverse ecological landscape. This island was located in the southern region of Central Java, whereas the island\u2019s natural reserve areas are located in the island\u2019s eastern and western regions . We surveyed several sites including (datum: WGS 84): Masigit Sela stream , Motean village , Mangunjaya stream , Lapas stream , Darmoko stream , Ketapang stream , and Kalidua stream .in-situ).We conducted a standard Visual Encounter Survey using purposive sampling methods , by nighWe identified the herpetofauna species by examining external morphological characteristics and consulting previously published literature that inhabits mudflats . The disturbance caused by humans to this habitat complex is relatively low.Mangrove forest type 2, is a forest composed of mangroves which has been associated with other lowland forest vegetations, characterised by water canals and small streams. The disturbance caused by humans is more pronounced in this habitat complex than in mangrove forest type 1 .Fishpond and settlement area, is a rural area characterised by the presence of small communities. The areas were adjacent to water canals and composed of shrubs, palm and coconut trees, fishponds, and human settlements. The disturbance caused by humans to this habitat complex is profound.Paddy field and timber production forest, is an area characterised by the presence of paddy fields and sparsely timber production forest that have not been logged by the communities. The area is not overly steep, and the disturbance caused by humans is significant.Edges between agriculture and forest, is the border between two distinct habitats, the agricultural area and the forest. The hills were excessively steep, the timber production forest was still present, and human disturbance is less significant than in paddy fields and timber production forests, as the area is distant from human settlement areas.Tributary stream and degraded areas, is an area primarily made up of small water streams that disembogued into canals; some areas are open due to harvested timber forest, and the water streams are mostly murky due to erosion and soil degradation. This habitat was typically found between the edges of agriculture and forest and lowland forest type 1; areas with a high level of human disturbance.Lowland forest type 1, is a natural habitat that is flowed by clear freshwater from karst caves, dense canopies, and is covered in a various vegetation. Typically, this area is accessible to locals in search of forest resources.Lowland forest type 2, is a pristine habitat fed by freshwater, with rocky terrain, dense canopies, and a wide and varied vegetation cover. The canopy was so dense that sunlight could not reach the forest floor thoroughly. This area was so secluded that the locals considered it inaccessible.Rhacophorus reinwardtii , Cyclemys dentata (NT), and Amyda cartilaginea (Vulnerable). Six highly traded species categorised in Appendix II were identified using Gekko gecko, Malayopython reticulatus, C. dentata, A. cartilaginea, Varanus salvator, and Crocodylus porosus. According to the PERMEN LHK list, our surveys identified one protected species, C. porosus. Currently, a total of 43 herpetofauna consisting of 16 amphibians and 27 reptiles \u20138 are reDuttaphrynus melanostictus , Singapore, Malaysia, Brunei Darussalam, Thailand, Cambodia, Myanmar, Lao PDR, Vietnam, India (including Andaman and Nicobar Islands), Bangladesh, Pakistan, Sri Lanka, Nepal, Bhutan, Maldives, Hong Kong and China (including Taiwan and Hainan); it is also found in Bali, Madagascar, Sulawesi, Ambon and New Guinea. Their habitat is inextricably linked to human settlement and disturbed area Distribution and habitat: This species is found throughout Indonesia, including Sumatra, Java, Bali and Nusa Tenggara. It may have been introduced to Sulawesi as well. It is found in primary and secondary forest at elevations of up to 700 m asl. The habitat is closely linked to human activity. However, in Java, it seems that this species is restricted to forested areas Distribution and habitat: It is known to occur on the Indonesian islands of Java, Kalimantan and Sumatra. There have also been reports of occurrences in Sarawak, Sabah, Peninsular Malaysia and Peninsular Thailand. It is mainly found in the leaf litter of moist forests less than 400 m asl. It is occasionally seen in marshy or wet areas with clear, slow-moving waters Distribution and habitat: It distributed throughout Thailand (including the provinces of Bangkok and Cholburi), Malaysia and Indonesia and was introduced into New Guinea and Guam. This species is found primarily in lowland rainforests, forest edges, lower montane forests, monsoon forests, brackish waterways, mangrove swamps and agricultural areas on Bali Distribution and habitat: It is found throughout South and East Asia, as well as Southeast Asia. Sumatra, Java, Kalimantan and Sulawesi comprise the Indonesian distribution. They inhabit wetlands, forests, savannah, grassland and man-made habitats such as paddy fields and urban areas Distribution and habitat: This species is endemic to Java\u2019s mountainous forest, where it is found primarily near slow- or moderate-moving water. They are frequently found near shallow water banks and crab nesting holes Distribution and habitat: This species is known to occur in Java and Sumatra of Indonesia. It is common along rivers and clear streams Distribution and habitat: This species is endemic to the Indonesian island of Java. It is found only in forested areas between 0\u20131400 m asl Distribution and habitat: This species is found throughout India, Bangladesh, Myanmar, Thailand, Cambodia and Lao PDR. Additionally, it is found throughout southern China, Vietnam, Malaysia and Indonesia . They are abundant in rice fields, submerged and floating with their bulging eyes visible above the surface of the water Distribution and habitat: This species is found only on the Indonesian islands of Java, Madura, Bali and Kangean. It is primarily found in forested areas and is easily found at elevations greater than sea level Distribution and habitat: This species is found only in West Java and western Sumatra, Indonesia. They are found in forest habitats at lower elevations Distribution and habitat: It is only found in Java of Indonesia. This species is restricted to primary and secondary forests, though it is occasionally encountered near human settlements up to an elevation of 1,600 m asl Distribution and habitat: It is found in Philippines and Indonesia , as well as Brunei Darussalam, Thailand and Malaysia (including Nicobar Islands). They are typically found near disturbed areas and slow-moving waters at the forest edge. It is found in Java up to 1,500 m asl Distribution and habitat: It is found in Java, Sumatra and Bali in Indonesia. It is found up to 1,200 m asl. It is frequently encountered in human settlements adjacent to bodies of water, where it thrives in stagnant waters, leaves, and nearby vegetation Distribution and habitat: Southern China, Indo-China, India, Philippines and Indonesia are all parts of this species\u2019 range. This species is frequently found in marshes and secondary forest ecosystems. This species is tolerant of areas subject to high levels of human disturbance Distribution and habitat: This species is found only on the island of Java, Indonesia. It is frequently encountered in primary and secondary forest habitats. It prefers higher elevations between 250 m asl\u20131,200 m asl , Malaysia, Singapore and India (including Assam), and was most likely introduced to Indonesia\u2019s Lesser Sunda and Sulawesi, as well as Yunnan of China. They are found in a variety of freshwater habitats and peat swamps Distribution and habitat: Freshwater turtles are found throughout Indonesia , the southern Malay Peninsula, and Phillipines . They prefer low plains and are frequently encountered in small rivers, shallow streams, and puddles Distribution and habitat: This huge reptile is found throughout Australia, Palau, Papua New Guinea, Philippines, Vanuatu, Micronesia, Indonesia , Malaysia, Brunei Darussalam, Singapore, Vietnam, Myanmar, Thailand, Cambodia, India, Sri Lanka and Bangladesh. This species is commonly found in estuaries Distribution and habitat: This species is found throughout Indonesia , as well as Philippines and Cambodia. It is found in lowland forests and open areas Distribution and habitat: This species is found only on the Indonesian island of Java. They are found in lowland forest habitats Distribution and Habitat: The gecko is found throughout Indonesia , Malaysia, Philippines, New Guinea, Singapore, Thailand, Myanmar, Lao PDR, Vietnam and Cambodia, and was probably introduced to Mexico, Cuba, Hawaii, Mauritius, Seychelles and Madagascar. This species is strongly associated with primary forest habitats as well as human settlements Distribution and habitat: This species is found throughout India, Bangladesh, Nepal, Bhutan, Thailand, Myanmar, Lao PDR, Cambodia, southern China, Vietnam, Malaysia, Philippines and Indonesia . Habitat is closely associated to the urban environment Distribution and habitat: The species is found throughout the tropics and subtropics. Its origins can be traced all the way back to Southeast Asia and the Indo-Australian archipelago. They are found in urban and forested areas and can be found up to 1,600 m asl . Habitats are associated with open areas, such as marshes and grassland, which are found primarily on mid-hills to low land up to an elevation of 850 m asl Distribution and habitat: This species is found throughout South and Southeast Asia, including India, Myanmar, Thailand, Vietnam, Cambodia, Lao PDR, Malaysia, Philippines and Singapore . It is found in open forest at elevations of up to 1,200 m asl. It is commonly found on large trees, particularly in the buffer zone Distribution and habitat: This species is found throughout Indonesia , Bangladesh, India, China, Taiwan, Thailand, Cambodia, Lao PDR, Myanmar, Vietnam, Peninsular Malaysia, Singapore, Timor-Leste and New Guinea. This species is found in a wide variety of habitats, including peat swamp forest, montane forest, disturbed riparian habitats, moist lowland, tropical dry, agricultural land, savannah, eucalyptus forest, coffee plantations, woodland and gardens up to an elevation of 1,800 m asl Distribution and habitat: It is distributed in India, Malaysia, Singapore, Philippines and Indonesia . Habitats are associated with forested areas in the mid-hills Distribution and habitat: This monitor lizard is found in Sri Lanka, India, Bangladesh, China, Thailand, Myanmar, Cambodia, Lao PDR, Vietnam, Malaysia, Singapore and Indonesia , where it is mostly found in swamps and riverbanks Distribution and habitat: This species is found throughout Southeast Asia, including China, Philippines, India, Bangladesh and Sri Lanka. This snake is found in primary moist lowland and montane forests, secondary forests, open and dry forests, disturbed forests, scrublands, and plantations, as well as city gardens and urban areas Distribution and habitat: This species was widely distributed across Southeast Asia. It is found in Sumatra, Java, Kalimantan and Sulawesi of Indonesia. Their habitat is primarily lowland forests, specifically mangrove swamps and peat swamp forests, which reach elevations of up to 700 m asl Distribution and habitat: This species is found only in West Java . This species is found in lowland to mid-hill forests at elevations ranging from 35 m asl\u2013990 m asl Distribution and habitat: This species is found throughout Indonesia, Timor-Leste, Brunei Darussalam, Malaysia, Thailand, Lao PDR, Vietnam, Cambodia and China. This species is typically found in lowland forests and at elevations of up to 1,000 m asl Distribution and habitat: This species occurs throughout Indonesia, Singapore, Malaysia, Thailand, Myanmar, Cambodia, Lao PDR, Vietnam, China, Taiwan, Bangladesh, India and Bhutan. The snake can be found in lowland to montane forests at elevations up to 3,000 m asl Distribution and habitat: This species is found throughout Asia and Southeast Asia, particularly in China, Myanmar, Thailand, Cambodia, Vietnam, Lao PDR, Malaysia and Indonesia . This species is found in lowland to submontane forests at elevations ranging from 550 m asl\u20131,300 m asl in the Ms.Malayopython reticulatus Distribution and habitat: This large constrictor snake is found throughout Southeast Asia, including Indonesia, Philippines, Malaysia, Thailand, Lao PDR, Vietnam, Myanmar, Cambodia and Bangladesh. It is found in a variety of habitats, including primary and secondary forests, savannah, shrublands, wetlands, peat swamps, mangrove swamps, grasslands, agricultural areas and urban areas. This species is found at elevations ranging from 0 m asl\u20131,300 m asl Distribution and habitat: It has been reported to occur in Indonesia as well as other Southeast Asian countries such as Myanmar, Thailand, and Malaysia. They inhabit lowland forests and agricultural areas between 500 m asl and 1,100 m asl and C. chalconota . Kls had the highest dominance index (0.44) due to high number of two species aforementioned , however, the dominance in most of the surveyed sites can be considered as low (D: \u2264 0.50).A total of 372 individuals comprising of 43 herpetofauna species were collected from the western part of Nusa Kambangan Island, from various sites, habitat complexes and/or vegetational types. en sites ; Table 2en sites due to tR. reinwardtii, C. dentata, A. cartilaginea, and X. javanicus, followed by paddy field and timber production forest with 16 species but mostly consisting of generalists such as F. cancrivora, F. limnocharis, C. chalconota, P. leucomystax, B. jubata, E. multifasciata, A. prasina, and D. pictus associated with the presence of specialists such as . pictus ; Table 3The average air temperature is between 26\u00b0C\u201330\u00b0C, and the average relative humidity is between 85%\u2013100% . Mss wasAccording to our surveys, the total herpetofauna species comprised 21% of the herpetofauna species found in Java and R. reinwardtii , can be used as bioindicators of environmental change or habitat disturbance. Additional research is required to ensure the effectiveness of community-based conservation, including local attitudes, participation, conservation awareness, and good governance.Another way to aid conservation efforts on Nusa Kambangan Island could be to conduct research on ecologically significant species . For insOur initial surveys on Nusa Kambangan Island\u2019s west part resulted in the identification of 43 herpetofauna species (16 amphibians and 27 reptiles). Our analyses indicate that Nusa Kambangan Island is capable of supporting suitable habitats for a diverse herpetofauna, but the habitats have been threatened by human disturbance. Community-based conservation efforts may provide an alternative method of conserving the island\u2019s biodiversity. We hope to encounter additional herpetofauna species in the future through additional surveys, particularly in the eastern part of Nusa Kambangan Island."} +{"text": "Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the demographic factors that are associated with OA diagnosis are well established, the factors that are associated with joint supplement use are not as well studied. Using data collected from the Dog Aging Project, we analyzed owner survey responses regarding joint supplement administration and OA diagnosis for 26,951 adult dogs. In this cross-sectional analysis, logistic regression models and odds-ratios (OR) were employed to determine demographic factors of dogs and their owners that were associated with joint supplement administration. Forty percent of adult dogs in our population were given some type of joint supplement. Perhaps not surprisingly, dogs of older age, larger size, and those that were ever overweight were more likely to receive a joint supplement. Younger owner age, urban living, owner education, and feeding commercial dry food were associated with a reduced likelihood of administration of joint supplements to dogs. Interestingly, mixed breed dogs were also less likely to be administered a joint supplement (OR: 0.73). Dogs with a clinical diagnosis of OA were more likely to receive a joint supplement than those without a reported OA diagnosis (OR: 3.82). Neutered dogs were more likely to have a diagnosis of OA, even after controlling for other demographic factors, yet their prevalence of joint supplement administration was the same as intact dogs. Overall, joint supplement use appears to be high in our large population of dogs in the United States. Prospective studies are needed to determine if joint supplements are more commonly administered as a preventative for OA or after an OA clinical diagnosis. Vaccinations, improved environment, and diet, as well as other preventative measures, have led to an increase in the numbers of dogs that reach \u201cold age\u201d , 2. As sOsteoarthritis (OA), the progressive degeneration in joints , is one The most common joint supplements in human populations are glucosamine and chondroitin . The exaWhile close attention has been paid to evaluating the effect of joint supplement administration in dogs with OA as well as the demographic factors associated with canine OA, much less is known about the factors that lead to joint supplement administration in dogs. Here, we use data collected from the Dog Aging Project to explohttps://www.dogagingproject.org, and all dogs living in the US are eligible to be enrolled, with the proviso that the owner must know the approximate age of the dog within a year or two. Participants are then able to access a password-protected DAP portal using the REDCap secure survey system (The Dog Aging Project (DAP) is a US-based nationwide long-term longitudinal study of the biological and environmental determinants of healthy aging in dogs . Client-y system , 24. They system . Once aly system . ApproxiAll analyses were completed in the program R, version 3.5.2 (www.r-project.org). Dogs under 1 year of age were excluded, as OA is generally an adult-onset disorder. Joint supplement use was defined as occurring in those owners that described their dog receiving one of the following supplements: glucosamine, an omega-3 fatty acid supplement, chondroitin, or \u201cother joint supplement\u201d. These choices were chosen as the three specific supplements are known to be commonly given , and bashttps://data.dogagingproject.org, as well in recently published studies on the dataset . We found that there was a significant association between breed and joint supplement administration , though as would be expected, small breeds had significantly fewer dogs on joint supplements than large breed dogs . We should note, however, that the number of neutered dogs vastly outnumber the intact dogs in our population (93.5% were neutered), described further in the discussion. In a multivariate model, age, weight, overweight status, neutering, and joint supplement administration were still significantly associated with a clinical diagnosis of OA that are associated with OA have been fairly well established, both anecdotally by veterinary clinicians and in the published literature , 13, wheInterestingly, the rates of joint supplement administration to companion dogs in the DAP appear to be much higher than in humans, where studies suggest around 20% of middle age and older adults take specific joint supplements , 32, thoThis study replicates previous findings that suggest old, large, neutered, and overweight dogs are more likely to have a clinical diagnosis of OA . In addiIn a previous retrospective study, we found significant associations between spay/neuter status and numerous disease diagnoses . Here, wThe lack of sex differences in OA is interesting given that in humans women have a higher OA prevalence than men . HoweverIn addition to many of the expected dog demographic factors associated with joint supplement administration, we also looked at demographics of the owners themselves to identify factors potentially influencing owner decisions to give joint supplements. We found owners in rural geographic regions were more likely to administer supplements to their dogs. In the DAP, we observe dogs living in rural environments appear to have higher activity levels compared to suburban and urban dogs , which cWe also find that owners that feed commercial dry kibble are less likely to administer joint supplements . There hPrevious studies of owner-provided supplements often focus on specific populations. In a small population of flyball dogs, it was found that 70% of owners provided joint supplements to their dogs , higher While our results are interesting and point toward some novel hypotheses on joint supplement use and OA in companion dogs, it will be necessary to follow up with longitudinal studies. First, as stated earlier, we do not know the direction of causality that underlies the correlation between OA and joint supplement use. Future longitudinal studies within the DAP will enable us to resolve the temporality. Similarly, OA diagnoses were owner-reported, so we do not know if these dogs had OA diagnosed by a veterinarian. Approximately half of all DAP participants have uploaded veterinary electronic medical records, so future studies will be able to verify these diagnoses. There also are differences across joint supplements, with omega-3s having more evidence of improved joint mobility than others like glucosamine \u201337. As wOverall, our results shed new light on both owner- and dog-specific factors associated with joint supplement administration to dogs. Future prospective studies will provide stronger evidence to discern if joint supplement administration is largely prophylactic or therapeutic. In addition, the DAP will enable us to follow those dogs that are currently receiving joint supplements with no diagnosis of OA to study if joint supplement administration is associated with lower risk of OA. As more companion dogs are surviving to older ages, the development of OA and joint supplement administration will most likely continue to increase in the population. Thus, there is great interest in future studies to tease apart the clinical utility of these supplements as well as educate owners about their use.https://data.dogagingproject.org.Publicly available datasets were analyzed in this study. This data can be found here: The University of Washington IRB deemed that recruitment of dog owners for the Dog Aging Project, and the administration and content of the DAP Health and Life Experience Survey (HLES), are human subjects research that qualifies for Category 2 exempt status . The patients/participants provided their written informed consent to participate in this study. Ethical review and approval was not required for the animal study because no interactions between researchers and privately owned dogs occurred; therefore, IACUC oversight was not required. Written informed consent was obtained from the owners for the participation of their animals in this study.1, Brooke Benton2, Elhanan Borenstein3, 4, 5, Marta G. Castelhano6, 7, Amanda E. Coleman8, Kate E. Creevy9, Kyle Crowder10, 11, Matthew D. Dunbar11, Virginia R. Fajt12, Annette L. Fitzpatrick13, 14, 15, Unity Jeffery16, Erica C. Jonlin2, 17, Matt Kaeberlein2, Elinor K. Karlsson18, 19, Kathleen F. Kerr20, Jonathan M. Levine9, Jing Ma21, Robyn L. McClelland20, Audrey Ruple22, Stephen M. Schwartz14, 23, Sandi Shrager24, Noah Snyder-Mackler25, 26, 27, Silvan R. Urfer2 and Benjamin S. Wilfond28, 29Joshua M. Akey1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, United States2 Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States3 Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel4 Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel5 Santa Fe Institute, Santa Fe, NM, United States6 Cornell Veterinary Biobank, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States7 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States8 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, United States9 Department of Small Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States10 Department of Sociology, University of Washington, Seattle, WA, United States11 Center for Studies in Demography and Ecology, University of Washington, Seattle, WA, United States12 Department of Veterinary Physiology and Pharmacology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States13 Department of Family Medicine, University of Washington, Seattle, WA, United States14 Department of Epidemiology, University of Washington, Seattle, WA, United States15 Department of Global Health, University of Washington, Seattle, WA, United States16 Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States17 Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, United States18 Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, United States19 Broad Institute of MIT and Harvard, Cambridge, MA, United States20 Department of Biostatistics, University of Washington, Seattle, WA, United States21 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States22 Department of Population Health Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States23 Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States24 Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, WA, United States25 School of Life Sciences, Arizona State University, Tempe, AZ, United States26 Center for Evolution and Medicine, Arizona State University, Tempe, AZ, United States27 School for Human Evolution and Social Change, Arizona State University, Tempe, AZ, United States28 Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA, United States29 Department of Pediatrics, Division of Bioethics and Palliative Care, University of Washington School of Medicine, Seattle, WA, United States.The DAP Consortium designed the DAP study, implemented data collection, and developed and curated the DAP databases. JH, MT, and DP designed the specific study. JH completed the analyses, made the figures, and wrote the first draft of the manuscript. All authors edited and approved the final manuscript.JH was funded by the National Institute on Aging Grant K99AG059920. The Dog Aging Project was supported by National Institute on Aging Grant U19AG057377 (PI: Promislow) and private donations.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.This content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Following the publication of this article and the Expression of Concern notice ,2, the KAll authors agreed with the retraction. LP, YF, FM, RM, and TS stand by the article\u2019s findings. LS and TS apologise for the issues with the published article."} +{"text": "Especially since the outbreak of COVID-19, the evolution dynamics and spatial mismatch of medical resources have been a focal and frontier issue in academic discussions. (2) Methods: Based on the competitive state model and spatial mismatch index, this paper uses GIS and Geodetector spatial analysis methods and three typical indicators of hospitals, doctors, and beds to conduct an empirical study on the evolutionary characteristics and degree of mismatch in the geographic pattern of health resources in China from 2010 to 2020 , in two dimensions of resource supply (economic carrying capacity) and demand . (3) Results: The spatial pattern of health resources at the provincial level in China has been firmly established for a long time, and the children and elderly population, health care government investment, and service industry added value are the key factors influencing the geographical distribution of health resources. The interaction between the different influence factors is dominated by bifactor enhancement, and about 30\u201340% of the factor pairs are in a nonlinear enhancement relationship. Hospital, doctor, and bed evolution trends and the magnitude and speed of their changes vary widely in spatial differentiation, but all are characterized by a high level of geographic agglomeration, heterogeneity, and gradient. Dynamic matching is the mainstream of development, while the geographical distribution of negative and positive mismatch shows strong spatial agglomeration and weak spatial autocorrelation. The cold and hot spots with evolution trend and space mismatch are highly clustered, shaping a center-periphery or gradient-varying spatial structure. (4) Conclusions: Despite the variability in the results of the analyses by different dimensions and indicators, the mismatch of health resources in China should not be ignored. According to the mismatch types and change trend, and following the geographic differentiation and spatial agglomeration patterns, this paper constructs a policy design framework of \u201cregionalized governance-classified management\u201d, in line with the concept of spatial adaptation and spatial justice, in order to provide a decision making basis for the government to optimize the allocation of health resources and carry out health spatial planning. Public health and well-being have been a frontier issue of academic research and the focus of social service work of government departments. Especially in the context of the COVID-19 outbreak , which h\u201cHealth China 2030\u201d Planning Outline to integrate health into all policies and safeguard and protect people\u2019s health in an all-round and full-cycle way. The central government\u2019s implementation of the \u201cHealthy China\u201d strategy requires local governments to optimize the allocation of health resources . The rationality of geographic distribution and spatial allocation of health resources has a great influence on the ability to protect and improve the health of the population. Therefore, it is of great significance to analyze the geographical pattern, spatio-temporal evolution dynamics, mismatch characteristics of health resources, and coping strategies for the formulating scientific health care policies, in order to plan and build a \u201cHealthy China\u201d .(1.(1RS) aThe spatial mismatch theory, created by Kain, was originally used to analyze the spatial mismatch between housing and employment of disadvantaged groups and is nThis paper analyzes the spatial pattern of health resources and their mismatch by means of spatial clustering analysis, cold and hot spots analysis, and exploratory spatial data analysis (ESDA), which are all data-driven unsupervised learning methods and do not require a priori knowledge. The spatial clustering analysis is conducted by quantile method, and the study area is divided into high, medium, and low levels to analyze the spatial heterogeneity of medical resources. In other words, sort the data in descending order, the top 10 belong to high, 11\u201320 belong to medium, and 21\u201331 belong to low. Provinces of the same level share a high degree of similarity, while those at different levels have significant differences. In this paper, regions in statistically significant clusters are identified using the cold and hot spots analysis tool, and the spatial autocorrelation between the evolution trends of health resources and types of mismatches is analyzed using ESDA and characterized using Moran\u2019s I. The global Moran\u2019s I value are in the range of , and a larger absolute value indicates stronger spatial autocorrelation. A value greater than zero indicates spatial positive correlation, less than zero indicates spatial autocorrelation, and equal to zero indicates random distribution . We diviGeodetector, created by Wang Jinfeng, a professor at the Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, and chief scientist of spatial analysis at the State Key Laboratory of Resource and Environmental Information System, is an emerging statistical analysis method for analyzing spatially driven mechanisms ,79. We uq and 22,565 (Inner Mongolia), 316,828 (Liaoning) and 187,106 (Jilin), and 188,100 (Zhejiang) and 113,000 (Fujian), respectively. In 2020, their thresholds are 35,447 (Hubei) and 25,616 (Jilin), 503,172 (Anhui) and 310,391 (Heilongjiang), and 361,300 (Zhejiang) and 216,800 (Fujian), respectively. In 2010 and 2020, the provinces of high level formed an \u201cX\u201d shaped agglomeration zone along Guangdong-Hebei and Sichuan-Jiangsu, including Guangdong, Hunan, Jiangxi, Hubei, Henan, Shandong, Shanxi, and Hebei. Provinces of medium level were distributed at the edge of the high-level zones, clustered in the Loess Plateau, Yunnan-Guizhou Plateau, Beibu Gulf, West Coast of the Strait, Yangtze River Delta, and northeast China. Most of the provinces of low level were clustered in northwest China, including Tibet, Qinghai, Xinjiang, Inner Mongolia, and Gansu . The GinThe change range of medical resources was characterized by clustering, and the spatial pattern of hospitals, doctors, and beds varied widely. Using the GIS spatial clustering quantile analysis tool, the change range of hospitals, doctors, and beds in 31 provinces from 2010 to 2020 were divided into three categories\u2014high, medium, and low. The thresholds were 3460 (Guizhou) and 1178 (Hubei), respectively. 212,640 (Guizhou) and 89,469 (Shanghai), 177,200 (Zhejiang) and 81,500 (Gansu). From the perspective of hospitals, the high-level provinces were clustered in the eastern coastal regions and the Yunnan-Guizhou Plateau in the southwest; the medium-level provinces were distributed in a zonal pattern along the western and northern borders, while the low-level provinces were mostly clustered in the central, central south, and Loess Plateau regions. Shandong had the largest number of new hospitals , compared to the largest number of hospital reductions (\u22123317) in Hunan, and Liaoning, Heilongjiang, Henan, Shaanxi, and Gansu provinces saw varying degrees of reductions in the number of hospitals. It is worth noting that the northeast and northwest regions, such as Liaoning, Heilongjiang, and Gansu not only have serious population loss problems, but also experienced negative economic growth. From 2010 to 2020, their hospital reduction, doctors, and beds increase, whether this complex change phenomenon is reasonable needs to be further analyzed by other methods . From the perspective of hospitals, the high-level provinces were clustered in the eastern coastal regions and Pan-Pearl River Delta urban agglomeration; the medium-level provinces were distributed in the middle of the two high-level clusters, and the low-level provinces were in north (including northeast and northwest) and west China. The largest number of new doctors was in Guangdong , while the smallest was in Tibet . From the perspective of beds, the high-level provinces covered most of the eastern and central regions, the medium-level provinces were distributed in the periphery of those of high level, mostly clustered in the Yunnan-Guizhou Plateau in the southwest and Loess Plateau in the northwest, and the low-level provinces were clustered in the west and north. The largest increase in beds was in Sichuan , while the smallest was in Tibet .The change speed of medical resources showed gradient agglomeration, and the high-middle-low level areas shaped a center-periphery spatial structure in geographical distribution. Using the GIS spatial clustering quantile analysis tool, the change speed of hospitals, doctors, and beds in 31 provinces from 2010 to 2020 were divided into three categories, i.e., high, medium, and low, with thresholds of 1.52% (Yunnan) and 0.75% (Jiangxi), 5.90 (Guangxi) and 4.75 (Henan), and 7.48% (Guangxi) and 5.87% (Hebei), respectively. In terms of hospitals, the high-level regions were scattered in distribution, including Guangdong, Hainan, Chongqing, Yunnan, Tibet, Shandong, Tianjin, Shanghai, Anhui, and Jilin. The medium-level provinces were on the periphery of those of high level, mostly clustered in west and north China. Most of the low-level provinces were clustered in central and south-central China, the Loess Plateau, and the Bohai Bay. Tibet recorded the largest average annual growth (3.41%), while Heilongjiang recorded the largest decline (\u22120.76%). The average of change speed for hospital was 1.14%, with 48.39% of provinces exceeding it. In terms of doctors, the high-level provinces were mostly clustered in the Yunnan-Guizhou Plateau in the southwest and the Qinghai-Tibet Plateau; the medium-level provinces were distributed in the periphery of those of high level, and the low-level provinces were distributed in north China . The largest average annual growth of doctors was in Tibet (9.41%), and the smallest was in Heilongjiang (1.69%). The average of change speed for doctor was 5.26%, with 45.16% of provinces exceeding it. In terms of beds, the provinces of high, medium and low level were clustered in a gradient distribution along the north\u2013south direction, with the largest annual growth in Guizhou (10.13%) and smallest in Beijing (3.19%). The average of change speed for bed was 6.16%, with 61.29% of provinces exceeding it.In the hospital dimension, star provinces were clustered in the eastern coastal regions, cow provinces were in the central region, question provinces were mostly clustered along the western border, and dog provinces were clustered in north China. The hot and cold spots were clustered along the east\u2013west direction in a gradient manner. Hot spot provinces were clustered in the middle and lower reaches of the Yangtze River, with secondary hot spots clustered in its periphery. Cold spot provinces were clustered in the northwest and northeast, with secondary cold spots clustered in north China, including Inner Mongolia, Shanxi, and Liaoning. Global Moran\u2019s I was 0.14, indicating a positive spatial autocorrelation. According to local autocorrelation analysis, HH- and HL-type provinces were only Sichuan and Henan, LL-type provinces included Hainan, Anhui, Fujian, and Shanghai, and LH-type regions included Gansu and Xinjiang .In the doctor dimension, most of the star provinces were clustered in southwest China, including Yunnan, Guangxi, Guangdong, Sichuan, Shaanxi, Jiangsu, and Zhejiang. The cow provinces were clustered in the central China and extended to Hebei and Shandong. The question provinces were scattered in distribution, including Hunan, Chongqing, Ningxia, Qinghai, and Tibet. Most of the dog provinces were clustered in north China, especially in the northeastern region. The hot and cold spots were clustered along the north\u2013south direction in a gradient manner. Hot spot provinces were clustered in the Yangtze River Economic Belt and its south, with secondary hot spots distributed in its periphery in the Yellow River Economic Belt. Cold spots were clustered in the northeast, with secondary cold spots clustered in the west, Beijing, Tianjin, and Hebei and their surrounding areas. Global Moran\u2019s I was 0.15, indicating a positive spatial autocorrelation. According to the local autocorrelation analysis, only Hebei was an HH-type region; HL-type provinces included Guangxi, Anhui, and Shandong, LL-type regions included Hainan, Jiangxi, Chongqing and Guizhou, and LH--type regions included Inner Mongolia, Heilongjiang and Jilin.In the bed dimension, the star provinces were clustered in the Yangtze River Delta and Pan-Pearl River Delta urban agglomeration, the cow provinces were clustered in the Bohai Bay, the question provinces were clustered in Qinghai-Tibet and Loess Plateau regions and the west coast of the strait, and the dog provinces were clustered in north China. The hot and cold spots were clustered along the north\u2013south direction in a gradient manner. Hot spot was clustered in clustered in south China, with secondary hot spots clustered in its periphery. The cold spot provinces were clustered along the border in west and north China, with secondary cold spots clustered in the middle and lower reaches of the Yellow River Basin and the Beijing-Tianjin-Hebei region. Global Moran\u2019s I was 0.23, indicating a positive spatial autocorrelation. According to the local autocorrelation analysis, only Liaoning was an HH-type province, HL-type provinces included Guangxi, Anhui and Shandong, LL-type provinces included Hainan, Jiangxi, Chongqing and Guizhou, and LH-type provinces included Gansu, Inner Mongolia, and Heilongjiang.The analysis of spatio-temporal evolution trend based on Boston Consulting Group Matrix contributes to revealing the change trend of health resource allocation, for the purpose of developing differentiated and adaptive management strategies for different provinces. The strategies for future health resource supply include three types of development, stability, and retrenchment. The development strategy is to invest in additional health resources, expand the medical resource supply, and improve health services. The stabilization strategy is to stabilize the current supply mode and allocation status without additional investment, try to maximize the value, and efficiently use of health resources. The retrenchment strategy is to scale back the supply of health resources and address the problems of waste or extensive use. In general, star provinces should adopt development strategy, cow provinces should adopt stabilization strategy, question provinces can selectively implement development, stabilization or retrenchment strategy based on their actuality, and dog provinces can selectively adopt retrenchment or stabilization strategy. It should be noted that all provinces should choose the most appropriate strategy to maintain or reverse the development pattern or trend, according to the health resource supply and demand balance (mismatch or adaptation) .(1)Spatial Mismatch Type of PopulationIn the hospital dimension, 61.29% of the provinces fell into the dynamic matching type in 2010, further expanding to 70.97% in 2020. In 2010, 22.58% of the provinces were of the positive mismatch type, distributed in the middle and upper reaches of the Yellow River Basin in clusters; by 2020 the cluster area shrank significantly, with most of them in the lower reaches of the Yellow River Basin. There were the same number of provinces belonging to the negative mismatched type in 2010 and 2020, but their geographical distribution was changed from random to agglomerative (Yangtze River Delta urban agglomeration) . In 2010p > 0.05, the same below), indicating a shift from positive spatial autocorrelation to no correlation. In the dimension of local spatial autocorrelation, Zhejiang, Fujian, Chongqing, Hubei, Guangxi, and Hainan were HH-type regions in 2010, which were changed to Shandong, Beijing, and Zhejiang in 2020. Inner Mongolia and Hebei were HL-type provinces in 2010, which were expanded to most parts of the country in 2020. Provinces of LH- and LL-types were scarce and distributed in a random manner, including Hunan, Jiangxi, Guangdong, and Hebei.In the doctor dimension, 67.74% of provinces fell into the dynamic matching type in both 2010 and 2020, covering the western, northern, and central regions of China. In 2010, 12.9% of the provinces were of the positive mismatch type and relatively concentrated in the Bohai Bay, compared to a random distribution in 2020, including Jilin, Beijing, Shandong, Shanxi, and Zhejiang. Provinces of the negative mismatch type in 2010 shaped a belt-like agglomeration in the Pan-Pearl River Delta in the east\u2013west direction and changed to a belt-like agglomeration in the north\u2013south direction in 2020. In 2010, the hot spots were clustered in north China and the Bohai Bay, with secondary hot spots clustered in their western and southern periphery. The cold spots were clustered in the Pan-Pearl River Delta urban agglomeration, with secondary cold spots only including Yunnan, Sichuan, Jiangxi, and Zhejiang. In 2020, the hot spots covered north China and northeast China and extended to the Loess Plateau in northwest China, with secondary hotspots clustered in the west. The cold spots were clustered on the southeast coast and extended to Hunan and Chongqing, with secondary cold spots clustered in central China, including Anhui, Jiangxi, and Hubei. The global Moran\u2019s I value for 2010 and 2020 were 0.15 and \u22120.10 *, respectively Mismatch Index Contribution Rate of PopulationIn 2010, the provinces with higher contribution to hospital mismatch were clustered in the center of China in a \u201cT\u201d shape, while the provinces of medium level were distributed in the periphery of the high level, and those of low level were distributed in the more peripheral northwest and northeast regions. High-medium-low level provinces shaped a closer center-periphery spatial structure in geographical distribution. In 2020, most of the provinces of high level were clustered in the eastern coast, the lower reaches of the Yangtze and Yellow rivers, with Jilin, Sichuan, and Shandong being isolated spots in the periphery. Provinces of medium level were clustered in the middle reaches of the Yangtze River and middle and upper reaches of the Yellow River, and those of low level were scattered in distribution, including Xinjiang, Qinghai, Ningxia, Heilongjiang, Liaoning, Fujian, Henan, Chongqing, Sichuan, Guangxi, and Hainan .In 2010, the provinces with higher contribution to doctor mismatch were clustered along Guangdong-Hubei-Liaoning in a north\u2013south belt, and those of medium level were distributed in its periphery, including Fujian, Jiangxi, Zhejiang, Heilongjiang, Jilin, Shanxi, Shaanxi, Guangxi, Hainan, and Yunnan. Provinces of low level were clustered along the Loess Plateau\u2013Qinghai-Tibet Plateau direction, including Gansu, Ningxia, Qinghai, Tibet, and Inner Mongolia. In 2020, three types of regions showed an east\u2013west gradient distribution. Provinces of high level were still in the north\u2013south belt-like agglomeration, but their regional coverage began to shrink, with those of medium level clustered in the middle area, and those of low level in the northwest and southwest China.In 2010, the provinces with higher contribution to bed mismatch were clustered in the central and coastal regions in an \u201cX\u201d shape, with those of medium of distributed in their periphery, as well as those of low level clustered in northwest China. Provinces of high level in 2020 were distributed in a band in the middle and upper reaches of the Yangtze River and the southeast coast, including Sichuan, Chongqing, Hubei, Hunan, Shandong, Fujian, Zhejiang, Hebei, and Liaoning. Most of the provinces of medium were clustered in the north and south of the high level, including Yunnan, Guizhou, and Guangxi in the southwest and Shaanxi, Henan, and Anhui in the central part of the country. Provinces of low level were mostly clustered in the Qinghai-Tibet Plateau and Loess Plateau, with a small number randomly distributed in the coastal areas, including Shandong and Jiangsu.(1)Spatial Mismatch Type of GDPIn the hospital dimension, 54.84% of the provinces fell into the dynamic matching type in 2010, further expanding to 64.52% in 2020. In 2010, 29.03% of the provinces fell into the positive mismatch type, mostly clustered in the middle and upper reaches of the Yellow River and middle reaches of the Yangtze River, but the cluster area shrank significantly to only the east and west ends by 2020. Provinces that fell into the negative mismatch type in 2010 and 2020 were essentially equivalent (about 15%), including Jiangsu, Zhejiang, and Guangdong . In 2010In the doctor dimension, about 50% of provinces fell into the dynamic matching type in both 2010 and 2020, with contraction in the north and expansion in the center. The same percentage of provinces were seen falling into the positive mismatch type in 2010 and 2020 (35.48%), mostly clustered in the Yunnan-Guizhou Plateau and Yellow River Basin. Provinces of the negative mismatch type in 2010 and 2020 were equivalent, clustered along the coast in a band. In 2010, the hot spots were clustered in the Yunnan-Guizhou Plateau in southwest China, with secondary hot spots clustered in the Loess Plateau and Beibu Gulf. The cold spots were clustered in the Shandong-Anhui-Zhejiang-Fujian region, with cold spots widely distributed. In 2020, the hot spots were clustered in the Yunnan-Guizhou Plateau\u2013Loess Plateau-northeast direction, with secondary cold spots mostly in Bohai Bay. The cold spots were clustered in the Pearl River Delta\u2013Yangtze River Delta region, with secondary cold spots clustered in the lower reaches of the Yellow River and west China (Tibet and Xinjiang). The global Moran\u2019s I value for 2010 and 2020 were 0.30 and 0.46, respectively, indicating a positive spatial autocorrelation with increasing strength. In the dimension of local spatial autocorrelation, Anhui fell into the HH-type in 2010, and no HH-type region was found in 2020. Provinces of HL-type were Yunnan and Guizhou in 2010, but expanded to Sichuan, Shaanxi, and Shanxi in 2020. In 2010, Tibet, Chongqing, and Hubei were LL-type regions, which were changed to Inner Mongolia, Liaoning, and Chongqing in 2020. The LH-type regions were clustered in the eastern coast, including Jiangsu, Shanghai, Zhejiang, and Fujian.In the bed dimension, 54.84% of the provinces fell into the dynamic matching type in 2010, expanding slightly to 58.06% in 2020, mostly clustered in west, north, and central China. About 35% of the provinces falling into the positive mismatch type in both 2010 and 2020, mostly clustered in the Yunnan-Guizhou Plateau and its surrounding areas. The regions that fell into the negative mismatch type were exactly the same in 2010 and 2020, including Jiangsu, Zhejiang, and Guangdong. In 2010, the hot spots were clustered in the Yunnan-Guizhou Plateau, with secondary hot spots clustered in the west of its periphery, the Loess Plateau, and Beibu Gulf. The cold spots included Zhejiang, Anhui, and Shandong, with secondary cold spots distributed in north, central, and south China as transitional zones. In 2020, the hot spots were still clustered in the Yunnan-Guizhou Plateau, with secondary hot spots clustered in the Loess Plateau and Beibu Gulf. The cold spots were clustered in the Yellow River and lower reaches of the Yangtze River, with secondary cold spots clustered in northwest, north, and central China. The global Moran\u2019s I for 2010 and 2020 were 0.15 * and 0.19, respectively, indicating a shift from spatial uncorrelation to positive autocorrelation. In the dimension of local spatial autocorrelation, only Anhui fell into the HH-type in 2010, and no HH-type region was found in 2020. In 2010, Tibet, Qinghai, and Chongqing fell into the LL-type, which was further expanded to Shanxi, Tianjin, and Jilin in 2020. Yunnan and Guizhou maintained their status as HL-type regions in 2010 and 2020. The LH-type regions were Shanghai and Fujian in 2010, which were expanded to the Yangtze River Delta and west coast of the strait in 2020.(2)Mismatch Index Contribution Rate of GDPIn 2010 and 2020, the provinces with high contribution to hospital mismatch were clustered in the Yangtze River Delta, Pearl River Delta, and upper and lower reaches of the Yellow River, with those of medium level distributed in their periphery, low level clustered in west and north China, and middle reaches of the Yangtze River Economic Belt. In 2010, the provinces with high contribution to doctor mismatch were clustered in the lower reaches of the Yangtze River, Yellow River, and south China, with those of medium level distributed in the periphery and extending northwest; those of low level clustered in the Qinghai-Tibet Plateau, the middle reaches of the Yangtze River, and northeast China. Provinces of high level in 2020 shaped a coastal agglomeration in the east and extended north to Henan and Hebei and west to Yunnan and Sichuan. Provinces of medium level were clustered in northeast and northwest China, with those of low level clustered in the Qinghai-Tibet Plateau and middle reaches of the Yellow River. The provinces with high contribution to bed mismatch in 2010 were scattered in distribution, including Jiangsu, Zhejiang, Henan, Beijing, Guangdong, Hunan, Yunnan, Sichuan, and Xinjiang. Provinces of medium level were relatively clustered in north China and Beibu Gulf, with those of low level clustered in the Qinghai-Tibet Plateau, central China and Bohai Bay. In 2020, most of the provinces of high level were clustered in a belt-like pattern along the coast, with those of medium level clustered in southwest China and Bohai Bay, and those of low level clustered in the west, north, and central China .p < 0.05). With the mean value as the threshold, the influence factor with a force greater than the mean is defined as the key factor; the one smaller than the mean is defined as an important factor, and the one not statistically significant is defined as an auxiliary factor.The driving forces of influence factors on hospitals, doctors, and beds differed significantly, with the mean values of 0.52, 0.79, and 0.72, respectively , Hubei, Guangxi (maintaining the cow trend), and Shandong (maintaining the star trend). Hebei, Hubei, Sichuan, and Shanxi have long been in positive mismatch, and they should adopt an expansion strategy to push the evolution trend from cow to star. Shanghai, Zhejiang, Jiangsu, and Guangdong have been in negative mismatch for a long time, and they should adopt a smart shrink strategy to reduce the growth rate and push the evolution trend from question to dog and from star to cow. In terms of doctors and beds, Beijing and Tianjin are in dynamic matching, and they should introduce a stable development strategy to maintain the dog evolution trend. Heilongjiang, Sichuan, Guizhou, and Yunnan have long been in positive mismatch, and they should adopt a smart shrink strategy in the future to maintain the evolution trend of dog or cow type, or to change from question to dog.The comparison of spatio-temporal evolution trends and spatial mismatch relationships reveals the rationality of health resource supply and allocation schemes in the provinces and their improvement directions. For example, Zhejiang attaches great importance to investment in medical resources and, in recent years, has implemented the \u201c13th Five-Year Plan\u201d for the development of health care and plan for the medical service system in the province, which has contributed to the allocation of health resources in Zhejiang as a growth pole in China (in the evolution trend of star type). However, the spatial mismatch shifted from dynamic matching to negative mismatch from 2010 to 2020, indicating a shift from balance to imbalance between the large supply of health resources and population demand, with supply outstripping demand and extensive use of health facilities and resources. For example, the slowdown in investment in doctors and beds in Hebei in recent years has led to their evolution trend of cow-type. Notably, the type of spatial mismatch changed from dynamic matching in 2010 to positive mismatch in 2020, indicating the problem of undersupply of health facilities and resources, with the shift of supply-demand equilibrium of health services to disequilibrium, as a result of the long-term low investment in health care resources. In addition, despite the different evolution trends of health resources, such as question in Beijing and Tianjin, cow in Liaoning and Jiangxi, and dog in Inner Mongolia and Fujian, they all remained long in supply-demand balance of hospital allocation (in dynamic matching in 2010 and 2020).In addition, it is an innovation to include spatial effects in the analysis of influence factors and measure their interaction effects in this paper. Unlike the published articles, this paper incorporates spatial heterogeneity and autocorrelation into the influence factor analysis, based on the geographic detector method, to measure the force of influence factors on the geographical distribution of medical resources and reveal the interaction effects of different influence factors, thus further improving the accuracy of the driving mechanism analysis. This paper finds that factors such as children and elderly population, health care government investment, service industry added value, high quality population, medical insurance fund expenditure, and government revenue have a great direct influence on the geographical distribution of health resources, which further validates the findings of some scholars. For example, Li , Zheng , and GuoTo improve the uneven geographical distribution and spatial mismatch of health resources is one of the major challenges facing the government health sector. The government should redesign the spatial allocation scheme of medical resources and improve the supply and demand of health services, based on regional heterogeneity and spatial mismatch, under the guidance of spatial justice and regional health planning theories ,117. TheIn the hospital dimension, Beijing, Tianjin, Fujian, Jiangxi, Hubei, Chongqing, Guizhou, Guangxi, Hainan, Yunnan, Tibet, Qinghai, Xinjiang, Ningxia, Shaanxi, Inner Mongolia, Liaoning, and Heilongjiang are of dynamic matching. Hebei, Shandong, Shanxi, Henan, Hunan, Sichuan, Gansu, and Jilin are of positive mismatch, and Guangdong, Shanghai, Jiangsu, Zhejiang, and Anhui are of negative mismatch. According to the development trend, the future policy design should follow the guidance as below: Beijing, Tianjin, Chongqing, Guizhou, Yunnan, Tibet, Xinjiang, Hainan, Guangdong, Jiangsu, and Zhejiang should continue to maintain high growth and focus on cultivating provinces with high potential by carefully analyzing the development drivers to promote them as regional medical service centers. Fujian, Qinghai, Ningxia, Inner Mongolia, Heilongjiang, Hebei, Shanxi, Henan, Hunan, and Sichuan should maintain their slow growth or reduction in quantity. Shandong, Gansu, and Jilin should implement contractionary policies for strict control of the amount of growth and reverse the development trend of high growth, in order to avoid the waste or risk brought about by blind investment. Shanghai, Anhui, Jiangxi, Hubei, Guangxi, Shaanxi, and Liaoning should introduce innovation policies and invest their limited resources primarily in new demand creation or new supply development.In the doctor dimension, Tianjin, Hubei, Hunan, Chongqing, Tibet, Qinghai, Xinjiang, Ningxia, Inner Mongolia, and Liaoning are of dynamic matching. Beijing, Shandong, Shanxi, Henan, Shaanxi, Gansu, Sichuan, Yunnan, Guizhou, Guangxi, Liaoning, and Jilin are of positive mismatch. Shanghai, Jiangsu, Anhui, Fujian, Jiangxi, and Guangdong are of negative mismatch. Hebei and Zhejiang are of double mismatch. According to the development trend, the future policy design should follow the guidance as below: Jiangsu, Fujian, and Guangdong should continue to maintain high growth and cultivate them into regional integrated medical service centers. Shanghai, Anhui, Jiangxi, and Shandong should increase investment to further boost growth. Tianjin, Hubei, Hunan, Xinjiang, Inner Mongolia, Liaoning, Beijing, Shandong, Shanxi, Henan, Gansu, Liaoning, and Jilin should maintain a slow growth or reduction in quantity, while Tibet, Qinghai, Ningxia, Shaanxi, Sichuan, Yunnan, Guizhou, and Guangxi should introduce contractionary policies to strictly control the amount of growth and avoid waste or risk from blind investment. The current medical resources in Hebei fail to meet the actual demand and are beyond the economic carrying capacity, so external support is required in the future policy design. The current medical resources in Zhejiang are already excessive and far below the economic carrying capacity, so it should control the new investment and consider increasing external medical aid or cross-regional supportive transfer payments in the future policy design.In the bed dimension, Beijing, Tianjin, Shandong, Anhui, Shanghai, Jiangxi, Hainan, Chongqing, Shanxi, Shaanxi, Ningxia, Qinghai, Tibet, Xinjiang, Inner Mongolia, and Jilin are of dynamic matching. Liaoning, Heilongjiang, Henan, Hubei, Hunan, Guangxi, Guizhou, Yunnan, Sichuan, and Gansu are of positive mismatch. Shandong, Fujian, Zhejiang, and Jiangsu are of negative mismatch. Hebei is of double mismatch. In light of the development trend, the future policy design should follow the guidance as below: Anhui, Jiangxi, Hainan, Chongqing, Shaanxi, Qinghai, Tibet, Fujian, Zhejiang, and Jiangsu should continue to maintain high growth. Shandong should increase investment to further boost its growth rate. Beijing, Tianjin, Shandong, Shanghai, Shanxi, Ningxia, Xinjiang, Inner Mongolia, Jilin, Liaoning, and Heilongjiang should maintain a slow growth or reduction in quantity. Henan, Hubei, Hunan, Guangxi, Guizhou, Yunnan, Sichuan, and Gansu should implement contractionary policies and strict control of the amount of growth, in order to avoid waste or risk brought about by blind investment. The current medical resources in Hebei fail to meet the actual demand and are beyond the economic carrying capacity, so external support is required in the future policy design.In general, differentiated and adaptive management strategies should be adopted, depending on the relationship between health resource supply and demand, in order to maintain sustainable evolution trends or reverse unsound ones. For example, Hainan, Chongqing, Tibet, Qinghai, Ningxia, and Xinjiang, in dynamic matching, should implement a stable development strategy, with no need to change their current health resource allocation policy and evolution trend. Sichuan and Henan, in positive mismatch, should implement an incremental expansion strategy. That is, they need to expand future investments in hospitals, doctors, and beds and drive the evolution trend to maintain or shift to question or star to address the problem of insufficient supply and to improve their health services and support capacity. Guangdong and Jiangsu, in negative mismatch, should implement a smart shrink strategy. In other words, it is necessary for them to reduce the future investment in health resources and promote the evolution trend to maintain or transform into dog or cow, in order to address the problem of oversupply and improve the efficiency of resource utilization. Hebei, Shanxi, Jilin, Heilongjiang, and Gansu, in double mismatch, should adopt an integrated control strategy. That is, due to the imbalance between the supply of health resources and population demand and the mismatch with economic carrying capacity, they should apply to the central government for inter-provincial transfer payments or medical assistance in the future to further improve their regional service capacity of health facilities and resources.Reducing the inequality of geographical distribution and spatial mismatch of medical resources is still a key policy goal of health authorities in most countries . Based oThis paper finds that the geographical pattern of medical resources in China is solid over time, and that the quantity of resources and its change amplitude and speed have high spatial agglomeration and differentiation. The spatio-temporal evolution of inter-provincial medical resources in China has become diversified, with similar regions having high geographic agglomeration and weak spatial autocorrelation, as well as a gradient distribution of cold hot spots in a core-periphery structure. Children and elderly population, health care government investment, and service industry added value are the key factors influencing the geographical distribution of health resources, while social consumption, government revenue, high quality population, and medical insurance fund expenditure are important factors. The interaction between the different influence factors is dominated by bifactor enhancement, and about 30\u201340% of the factor pairs are in nonlinear enhancement. Although per capita GDP, urbanization rate, and residents\u2019 medical services consumption do not have statistically significant direct influence, they have high interaction influence with other factors as auxiliary factors that cannot be ignored. Most of the provinces\u2019 medical resources are in dynamic matching, mainly concentrated in west and north China and the middle reaches of the Yangtze River. A path-dependent strategy should be adopted in the future policy design to maintain the current development. The mismatch in the supply of medical resources in China is more serious than that in demand, and the proportion of mismatch in hospitals and beds is decreasing; however, the opposite is true for doctors. For the regions of positive mismatch, hospital demand mismatches and hospital, doctor, and bed supply mismatches are clustered, while doctor and bed demand mismatches are randomly distributed, so smart contraction-type strategies should be adopted in the future policy design to moderately control the supply of new medical resources and avoid the waste of resources or investment risks. For the regions of negative mismatch, doctor and bed demand mismatches, as well as doctor, hospital, and bed supply mismatches, are clustered in bands, while hospital demand mismatches are randomly distributed, so smart growth-oriented strategies should be adopted in the future to increase the supply and investment in new medical resources to achieve sustainable development. The hot and cold spots of supply and demand mismatch are highly clustered, shaping a spatial structure of center-periphery or gradient change. Hospital demand mismatches and hospital, doctor, and bed demand mismatches all have positive spatial autocorrelation and are increasingly spatially correlated and dependent; however, doctor and bed demand mismatches have changed from positive spatial autocorrelation to uncorrelation.This paper is innovative in two areas. First, it introduces the spatial mismatch index to quantitatively measure the degree and type of medical resource mismatch at the provincial level in China from both the supply and demand perspectives and proposes a method for designing differential management policies, based on spatial zoning, which provides a basis for evidence-based decision making in health planning. Scholars are currently focusing on the study of mismatch of mobile factor resources, such as labor, capital, and commodities, and the immobility of health resources makes it more difficult and costly to correct their mismatch problems. In developing countries with limited health resources, incorporating economic carrying capacity and population demand power into health resource allocation models and health economics and desiIn addition, this study is applicable to China; it also has great reference value for developing countries, such as Iran, Egypt, Ethiopia, South Africa, Tanzania, India, Malaysia, and Mongolia. As described above, they have very limited medical resources, with a striking problem of uneven geographical distribution and spatial mismatch. An empirical study of these countries, using the research framework and methodology provided in this paper, can help them design differentiated and adaptive health resource management policies. It should be noted that interest games and institution settings play an important role in the allocation of medical resources , but the"} +{"text": "Alzheimer\u2019s disease (AD), due to its spread, has become a global health priority, and is characterized by senile dementia and progressive disability. The main cause of AD and other neurodegenerations are aggregated protein accumulation and oxidative damage. Recent research on secondary metabolites of plants such as polyphenols demonstrated that they may slow the progression of AD. The flavonoids\u2019 mechanism of action in AD involved the inhibition of acetylcholinesterase, butyrylcholinesterase, Tau protein aggregation, \u03b2-secretase, oxidative stress, inflammation, and apoptosis through modulation of signaling pathways which are implicated in cognitive and neuroprotective functions, such as ERK, PI3-kinase/Akt, NFKB, MAPKs, and endogenous antioxidant enzymatic systems. This review focuses on flavonoids and their role in AD, in terms of therapeutic potentiality for human health, antioxidant potential, and specific AD molecular targets. Alzheimer\u2019s disease (AD) is the most common cause of senile dementia associated with progressive disability. The inherited disease, in an autosomal dominant way, generally leads to a lethal outcome after about 5\u201310 years from the onset of the first symptoms . GeneralOxidative stress is defined as an imbalance between oxidants and antioxidants that causes a rise in oxidant levels . AccordiTherefore, while the brain membrane phospholipids are composed of polyunsaturated fatty acids, this organ is particularly vulnerable to free radical attacks. Plasma levels of thiobarbituric acid are high in the early stages of AD ; lipid hProteins are major targets of reactive oxygen species (ROS). Protein oxidative modifications can induce unfolding or conformational changes that can lead to the loss of specific protein function and the Nucleic acid damage also occurs early in AD. Significantly elevated levels of 8OHG and 4,6-diamino-5-formamidopyrimidine have been reported in post-mortem MCI brains relative to the age-matched controls . In addiAside from its presence in CNS, A\u03b2 can be detected in platelets and blooRecent studies have tested the power of natural compounds derived from plants against AD. Among these, flavonoids are ubiquitous compounds of plants, produced by plants for growth and defense against all kinds of stress, including cold tolerance. More than 6000 different flavonoids have been identified, the primary sources of which are apples, red fruits, onions, citrus fruits, nuts, and beverages such as tea, coffee, beer, and red wine. These compounds, derived from phenol, are particularly interesting for their ability to cross the blood\u2013brain barrier and for their multi-target activity. Several studies have described flavonoids to exhibit relevant biologic activities involving the neuronal antioxidants, as well as anti-amyloidogenic properties, acting as metal chelators, showing anti-inflammatory properties, and ameliorating cognition and neuroprotection ,50,51,52From a chemical point of view, flavonoids consist of two benzene rings, called A and B, linked via a third pyranosic ring C. Flavonoids can be divided into a variety of subclasses that differ in terms of the structural characteristics of the B ring and the degree of hydroxylation and glycosylation of the third ring. Typically, ring B binds in position 2 on ring C, but can also bind in position 3 or 4. We can, therefore, distinguish the isoflavones in which the B ring binds in position 3 of the C ring and the neoflavonoids in which the B ring binds in position 4 of the C ring . The groIn general, since all flavonoids contain the same core scaffold, the functional differences between the various groups and subgroups are mainly due to the different substituent groups. These are weak polybasic acids of a polyphenolic nature, characterized by varying degrees of hydroxylation, methoxylation, glycosylation or glucuronidation, and this contributes to the great variety of biological properties of this large group of polyphenols ,60. In fFlavonoids are a wide group of secondary metabolites characterized by many interesting biological potentials, both in vitro and in vivo and, in the last decades, they have emerged as a promising agents for neuroprotection ,66,67,68Flavonoids are widely distributed in the plant kingdom, and are characterized by chemical structures with the presence of several substituents that allow them to assume particular activities and exert beneficial effects for the wellness of organisms, as well as for their potential for therapeutic utilization. This does not indicate that every type of flavonoid is able to show biological potential, but only that those with particular characteristics can be employed for specific roles. For instance, one of the well-known and best-studied activities of flavonoids is its antioxidant activity, which is linked to the number of hydroxyl groups on the B ring. Generally, a greater number of free hydroxyl groups corresponds to a greater scavenging effect, but their location in the skeleton of flavonoids is a crucial structural element. These hydroxyl groups, through the donation of hydrogen atoms and electrons to radical species, favor the repair of the damage caused by ROS and reactive nitrogen species (RNS), reducing their degree of reactivity ,71. ThisThe ability of flavonoids to cross the blood\u2013brain barrier suggests that these compounds can feasibly have a direct effect on the brain. Numerous studies have documented the bioactivity of flavonoids against neurodegenerative disorders such as AD, Parkinson\u2019s, Huntington\u2019s, and other neurological disorders ,91,92,93Flavonoids, including epicatechin-3-gallate, gossypetin, naringerin, quercetin, and myricetin are reported to block \u03b2-amyloid and Tau aggregation, scavenge free radicals, and sequester metal ions at clinically low concentrations ,99. In oQuercetin is a polyhydroxyflavonoid that belongs to the subclass of flavonols. Its chemical name is 3,3,4,5,7-pentahydroxyflavone, and the molecule contains five -OH groups, in positions 3, 3\u2032, 5, 7 and 4\u2032, which are crucial for potential biochemical\u2013pharmacological activities. Quercetin is a natural antioxidant, widely used in healthcare for its beneficial role. Quercetin is found in flowers and fruits of edible plants; onions, apples, cherries, berries, asparagus, and red leaf lettuce have the highest levels, while tomatoes, peas, and broccoli have lower levels ,93. Expe2O2-induced p53 expression, and also significantly reduces apoptosis and caspase 3 activation [More specifically, Tau phosphorylation is under the control of several distinct kinases, such as Erk, Akt, p38, AMP activated protein kinase (AMPK), glycogen synthase kinase 3 beta (GSK3\u03b2), cyclin-dependent kinase 5 (cdk5), and protein phosphatase 2A (PP2A) ,103. Thrtivation . p53 regtivation ,110. In tivation ,110. In tivation ,112. A ttivation ,115,116.Hung et al. demonstrated that quercetin (10mM) pretreatment of human umbilical vein endothelial cells (HUVECs) suppressed the nuclear factor- kB (NF-kB) signal, suggesting that the drug is a powerful antiatherosclerotic . In addi2O2) and protein carbonyls levels, have been demonstrated [Naringenin is the aglycon of naringin, and belongs to the subclass of flavanones. It is abundant in citrus fruits , as well as vegetables, and especially in grapes, tomatoes, and cherries. Naringenin can be found in two forms. One is characterized by a bond with a sugar on C7, and one derives from the action of specific enzymes which are able to cleave this glycosidic bond by releasing the aglycone ,126. Botnstrated ,139,140.2O2 to chicken lymphocytes. After preincubation with EGCG, the compound restored H2O2\u2032s harmful effects, suppressing the increase of ROS and restoring the antioxidant system by mRNA expression of SOD, CAT, and GPx [Epigallocatechin-3-gallate (EGCG), an ester of epigallocatechin and gallic acid, is the main bioactive polyphenol found in solid green tea extract ,142. EGC and GPx . EGCG en and GPx . In Figu2+ and Fe2+; this, on the one hand, strongly enhances its antioxidant activity, because the Fenton reaction is inhibited and, consequently, the ROS generation is reduced. On the other hand, myricetin acts directly on A\u03b2 complexes, reducing their toxicity through the reduction in metal ions that can interact with them [Myricetin is a natural flavanol widely distributed in several vegetables and fruits, mainly including blackcurrant teas, red wines, and medical herbs ,155,156.ith them ,176,177.ith them . Finallyith them ,180. In Gossypetin is a flavonol isolated from the flowers and the calyx of Hibiscus sabdariffa. Gossypetin has been shown to exert antioxidant, antimutagenic, antimicrobial, and anti-atherosclerotic activities ,183,184.Genistein is an isoflavone distributed in several vegetables such as legumes, green peas, and peanuts, and is predominantly extracted from the Glycine max soybean ,187. SevThe antioxidant effects of genistein are associated with AMPK activation and the drug\u2019s binding with estrogen receptor \u03b1 (ER\u03b1), both of which promote the expression of antioxidant enzymes such as SOD, CAT, and GPx ,199,200.Apigenin formally belongs to the flavone subclass, and is widely distributed in the plant kingdom, present principally in chamomile flowers. and in lower concentrations in vegetables, citrus fruits, herbs, and plant-based beverages . In a raCyanidin 3-O-glucoside belongs to the anthocyanins class; it is present in plants such as berries and soybean fruits, where it is responsible for the red, purple, and blue pigments. Cyanidin has been reported to act as neuroprotector in several disorders, such as AD, Parkinson\u2019s disease, and multiple sclerosis ,214,215.Unfortunately, there is still a lack of translational research and clinical evidence for these promising compounds, and we found only one clinical trial, which began in 2022 and will finish in 2024, studying the efficacy and safety of the Flos Gossypii flavonoid tablet in the treatment of Alzheimer\u2019s disease . A totalThis review provides evidence that flavonoids have potential for treating AD, and are considered drug candidates for future clinical research. Although precise mechanisms are still unclear, flavonoids regulate several important physiological responses, which may contribute to neuroprotective effects in AD. The advantage of flavonoids over conventional targeting drugs is the possibility of administering these molecules as food supplements. Supplementation with flavonoids could allow for early protection, even at a young age. They can also be used without the need for a preclinical diagnosis, due to their low toxicity. Certainly, further long-term dietary intervention studies indicating the dosage and the times of drug assumption may contribute to fully evaluating the effectiveness of flavonoids as agents for the management of AD. It will be important to incorporate bioavailability and metabolism into experimental planning at all stages of preclinical research, in order to better clarify such mechanisms in vivo."} +{"text": "Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a neurovascular condition characterized by a severe sudden-onset headache that may be associated with focal neurological deficits. On imaging, the suggestive finding corresponds to multifocal vasoconstriction of the cerebral arteries, with a spontaneous resolution of approximately 12\u00a0weeks. The identification of precipitating factors and diagnosis must be carried out early, so that adequate management is established and the patient has a good prognosis, given the risk of secondary complications and residual neurological deficits. This study consists of a literature review based on the analysis of articles published between 2017 and 2022 in PubMed, SciELO, and ScienceDirect on RCVS, intending to understand the clinical and radiological characteristics, diagnosis, treatment, and prognosis of patients with RCVS. The pathophysiology, drug management, and prognosis still lack solid evidence; therefore, further studies on RCVS are needed to expand medical knowledge and avoid underdiagnosis and inadequate treatment of this important condition. The Reversible Cerebral Vasoconstriction Syndrome (RCVS) is characterized by sudden headache and reversible multifocal cerebral vasoconstriction \u20134. It isThe most common manifestation is thunderclap headache, which has a sudden onset and peak intensity in 1 min , 12, 13,Reversible Cerebral Vasoconstriction Syndrome should be suspected when there is a history of sudden headaches with normal physical examination, cranial tomography (CT), and magnetic resonance imaging (MRI) of the head , 12. GivOnce the diagnosis is established, treatment should be initiated, mainly by discontinuing the triggering factor, if known , 13, 19,As the wrong or delayed diagnosis of RCVS usually results in unnecessary diagnostic tests, deleterious treatments, and increases the risk of neurological sequelae , 5, 21, This article presents a literature review based on scientific articles published from 2017 to 2022 in PubMed, SciELO, and ScienceDirect on RCVS.In the first step of the methodology, a search was carried out in Pubmed, SciELO, and ScienceDirect databases with the title \u201creversible cerebral vasoconstriction syndrome\u201d and the filters \u201ccase reports\u201d, \u201cmulticenter study\u201d, \u201cobservational study\u201d, \u201creview\u201d, and \u201csystematic review\u201d were applied. In addition to these filters, only studies involving humans and those published in the last 5 years were selected. The article should be available and in English. A total of 129 articles were found in PubMed, three in SciELO, and 30 in ScienceDirect , those with an impossibility of access (seven articles), or those that did not contain information relevant to the topic (four articles). A total of 74 articles remained at the end of this stage.In addition, 11 new articles were selected and manually added according to their relevance to the study. Therefore, a total of 85 articles were included in this study.Reversible Cerebral Vasoconstriction Syndrome, also known as Call-Fleming Syndrome, postpartum angiopathy, migrainous vasospasm, and benign central nervous system angiopathy , 24, 25,Radiologically, the disease is characterized by multifocal vasoconstriction of the cerebral arteries that can lead to multiple infarctions and usually resolves spontaneously within 3 months , 33\u201337. The largest studies suggest that 50\u201380% of patients will have a secondary cause for RCVS , 41, 44.Nasal decongestants, immunosuppressants , 29, 48,The puerperium is responsible for 10\u201350% of cases \u201311, 45. Posterior reversible encephalopathy syndrome (PRES) is a disease that can occur simultaneously with RCVS and many studies suggest overlapping pathophysiological mechanisms , 41. FurAlthough the cause of RCVS is not yet fully detailed in the literature, most studies point to a transient dysregulation in the control of brain vessel tone, which results in multifocal vasoconstriction , 57. It Thunderclap headache has a reported prevalence between 95% and 100% in individuals diagnosed with RCVS and may In addition to headaches, patients often experience nausea, vomiting, photophobia, and phonophobia , 8, 10. Less frequently, RCVS may present with non-thunderclap and nonspecific headaches. It can be a single, recurrent, or progressive episode, and pain intensity varies from moderate to severe. There are also reports of patients who do not have any headaches , 65. TheReversible Cerebral Vasoconstriction Syndrome diagnosis is based on compatible clinical history, physical examination, and neuroimaging tests showing multifocal segmental vasoconstriction of cerebral arteries. Within 3 months, reversibility of this vasoconstriction occurs, evidenced in neuroimaging, however, some patients may persist with clinical deficits as well as complications, such as ischemic lesions and cerebral hemorrhage , 62, 64.The physical examination may be normal, but in some cases, there are neurological deficits that contribute to the suspicion, such as aphasia, hemiparesis, ataxia, and visual changes .Complementary laboratory tests such as a blood count, electrolyte analysis, and liver function tests are usually normal. However, inflammatory markers may occasionally be elevated when associated with a precipitating disease. Therefore, serum and urine drug toxicology should also be performed to screen for substances precipitating vasoconstriction . CerebroAs for imaging, digital subtraction angiography is the gold standard method, but it is invasive and can lead to complications , 13, 41,The characteristic diagnostic finding is the presence of \u201cbeading\u201d or \u201cpearls on a sting\u201d in the cerebral arteries, which corresponds to the alternating pattern of intense vasoconstriction and dilatation observed , 17, 20.Although there is still no universal diagnostic criterion established , 17, 62,Reversible Cerebral Vasoconstriction Syndrome is contained in the group of diseases known to have a thunderclap headache. This group includes stroke, SAH, cervical artery dissection, intracranial aneurysm, cerebral venous thrombosis, and hypertensive crisis , 56, 73.Posterior reversible encephalopathy syndrome is also part of the set of diseases present in the differential diagnosis of RCVS , 68, 71.In addition, vasospasm secondary to SAH is also a differential diagnosis. Both RCVS and vasospasm secondary to SAH present severe headaches and occur more frequently in middle-aged females. On CT angiography, both conditions demonstrate subtle differences in segmental vasospasm .The treatment needs, initially, to go through discontinuation of the triggering factor of the symptoms, if known, such as illicit drugs, aggressive vasoactive drugs, and Valsalva maneuvers , 13, 46.In drug treatment, according to case reports and expert analyses, symptomatic patients are recommended to use multimodal analgesia, CCBs, antiepileptics in case of epileptic seizures, and antiemetics as necessary , 20. NonRegarding CCBs, intravenous and oral nimodipine, with a dosage of 30\u201360\u00a0mg every 4 h , is bestHowever, although nimodipine is usually the first choice for the treatment of RCVS, it has not been shown to improve long-term outcomes or prevent complications , 20, 41.The other choices of CCBs are verapamil and nicardipine , 76 oralIn addition to BCCs, headache is controlled by analgesics, such as aspirin, although there is still no strong evidence of the clinical efficacy of this use . In anotTherefore, it is worth noting that no guidelines or data from randomized studies are available in the literature to guide the management of RCVS effectively , 20.Reversible cerebral vasoconstriction syndrome has several complications, which include PRES, epileptic seizures, ischemic stroke, SAH, and intraparenchymal hemorrhage (IPH) , 67, 79.Posterior reversible encephalopathy syndrome, one of the most reported complications in the articles read in this review, has an incidence in RCVS ranging from 8% to 38% , 43, 66.Ischemic and hemorrhagic complications have also been reported in many studies in the scientific literature, leading to persistent neurological deficits and death in more severe cases , 30, 43.Stroke is also a complication associated with RCVS and usually occurs up to 3 weeks after the syndrome , 79. It Cognitive impairment, which may result from stroke, has been little described in the literature. In a case report, a 36-year-old female patient, after being diagnosed with RCVS, presented deficits in autobiographical memory, cognitive flexibility, verbal and non-verbal learning, and information processing. The involvement was verified bilaterally in the frontal and temporal lobes and in the same region of the vasoconstriction observed in the MRI .The prognosis of RCVS is uncertain, but most patients have self-limiting manifestations , 11, 28 In the literature, there are still reports of recurrence of RCVS , 62, 83,However, some patients remain with a chronic daily headache that is difficult to treat, since many medications to relieve these symptoms are triggering factors for RCVS . FurtherDue to the facts mentioned above, the main precipitating factors for RCVS are the postpartum state, nasal decongestants, and drugs with vasoactive properties. This understanding is fundamental to guide the treatment, since, initially, aggravating factors for the patient should be discontinued. In addition, although nimodipine is the drug of choice in most studies, in some cases, other drugs, such as verapamil and nicardipine, have better efficacy. The patient diagnosed with RCVS, especially combining the clinic with imaging tests, such as angiography, must undergo a thorough medical follow-up to avoid the appearance or, at least, the worsening of already known complications resulting from the syndrome."} +{"text": "Correction to: European Radiology10.1007/s00330-022-09154-yThe original version of this article, published on 14 October 2022, unfortunately contained a mistake. The affiliation of the author Giuseppe Palma was incorrectly given as \u2018Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy\u2019 and has now been corrected to \u2018Institute of Nanotechnology, National Research Council, Lecce, Italy\u2019. The original article has been corrected."} +{"text": "INAA was chosen for its ability to perform elemental analysis without any preliminary sample treatment that could introduce systematic errors. The distribution of major elements was relatively uniform, with the sampling locations having less influence. Concerning the trace elements, excepting the PCE Cr, Ni, Cu, Zn, As, and Sb, their distributions presented the same remarkable similarity to the Upper Continental Crust (UCC), North American Shale Composite (NASC), Average Bottom Load (ABL), and Average Dobrogea Loess (AVL), and were in good concordance with the location of the Serbian Danube River in the Pannonian Plain. In the case of considered PCE, both Enrichment Factor and Pollution Load Index showed values higher than the pollution threshold, which pointed towards a significant anthropogenic contamination, and rising concern to what extent the water quality and biota could be affected.To determine the nature and origin of the unconsolidated bottom sediments, as well as to demonstrate and quantify the presence of Presumably Contaminating Elements (PCE) in the Serbian Danube River, as a novelty, the mass fractions on nine major elements as oxides\u2014SiO Within it, the Serbian section, which begins at the Serbian\u2013Hungarian border and ends at the confluence with Timoc River at the Serbian\u2013Bulgarian border, has a length of 588 km, i.e., 20.6% of the total river length [The Danube River, with a total length of 2857 km and a catchment basin of 817,000 kmAccording to its geomorphology, the Serbian section can be divided into three units, e.g., the Pannonian Danube between the Serbian\u2013Hungarian border and Golubac, with a length of 391 km; the Iron Gate Danube between Golubac and Kladovo, with a length of 111 km; and the Lover Danube between Kladovo and Serbian-Bulgarian border on Timok River, with a length of 86 km .The Pannonian unit, which flows the Pannonian Basin, presents typical characteristics of a low-gradient fluvial river, such as a sandy riverbed, bifurcating courses with numerous meanders, sand islands, and sandbars. Sedimentary material shows a well-evidenced stratification, which should reflect also the Pannonian Basin geochemistry and mineralogy, the main source of depositional material.The second two units of the Serbian Danube River have significantly changed as a result of the construction of the Iron Gate Hydropower and Navigation System (IGHPNS), comprising two large dams, one at km. 943 and the other downstream at 862.8. These created two reservoirs that extended upstream of the dams by 300 and 80 km, respectively . Both daRegarding sediments, excepting the Danube River at the entrance in Serbia, there are another three important sources of depositional material transported by the Tisa, Sava, and Velika Morava, the main Danube tributaries along Serbian Sector . Given sIndeed, according to , the maiThe origin of depositional material can be attributed, in different proportions, to the bedrock lithology, of which age is known, while the rest of sedimentary material can be considered a mixture of different components, of which exact origin, due to a continuous erosion and deposition, could not be exactly traced back. According to , the bedAnother peculiarity of the investigated sector of the Danube River is related to the presence of human agglomeration centers, such as Novi Sad, with over 365,000 inhabitants [For this reason, in recent decades, the anthropogenic contamination of the Serbian sector of the Danube catchment basin, and especially Danube and Sava River sediments, has been the subjects of an appreciable number of studies ,13,14,15Besides the presence and quantification of PCE, the geochemistry of the Serbian sector of the Danube River has been less investigated, although this aspect is worth attention, taking into account that, according to , at the To fill this gap, 13 samples of unconsolidated superficial sediments were collected along the Serbian sector of the Danube River between Belgrade and Iron Gate 2 dam, including the confluence of Sava, Velika Morava, and Pek tributaries . All samFor a better understanding of sediment geochemistry, we have reported our data to some general systems, such as Upper Continental Crust (UCC) , North AGiven the diversity of depositional material sources, as well as the presence of urban and industrial potential contamination along the Serbian sector of the Danube River and its tributaries, the main goals of this study were:(i) To evidence any similarities or dissimilarities between the geochemistry of Danube River sediments (Serbian Sector) and crustal material, such as UCC and NASC(ii) To quantify the contribution to environmental contamination of those PCE of which mass fractions were determined by INAA;Therefore, a related achievement of these objectives represents, in our opinion, a new approach, able to understand not only the geochemistry of Danube sediments in relation to their location, but also to evidence to what extent this sector of the Danube river is affected by anthropogenic contamination.The results of our study performed under these circumstances will be further presented and discussed.To accomplish this project, 11 samples of surface sediments (0\u201315 cm deep) and two samples of deeper sediments were collected between Belgrade and the Iron Gate 2 dam . The sedhttps://www.fritsch-international.com/ (accessed on 1 September 2022)) at 400 rpm. After that, from each homogenized sample, six aliquots of about 0.1 g were selected and irradiated at the IBR-2 reactor to be independently investigated via INAA.At FLNP, all sample processing and INAA measurements were performed in the Sector of Neutron Activation Analysis and Applied Research (SNAAAR). Here, each sample was again homogenized for 15 min using a PULVERISETTE 6 planetary ball mill ) software and processed using a proprietary software [After irradiation, gamma spectra were recorded using a HPGe detector with a 1.9 keV resolution for the software . This pesoftware , calculaSpecial attention was paid to quality control. This was done by simultaneous use of more Standard Reference Materials (SRM), e.g., 1633c-Coal fly ash, 667-Estuarine sediment, 2710-Montana Soil, and 1547-Peach leaves, as well as 2709-Trace elements in soil, 1632c-Trace elements in coal, 690CC-Calcareous soil, 2709a-San Joaquin soil, and SRM-AGV2\u2013Andesite for short- and long-living isotopes .Furthermore, all of them were reunited by forming the Group of Standard Sample (GSS) proprietary software ,31, withTM (https://www.statistica.com/en/ (accessed on 1 September 2022)) and PAST 4.09 [For a better description and characterization of the experimental data in relation with closer systems, such as UCC , NASC 22, ABL 2, and ADLAST 4.09 softwareThe experimental INAA data, e.g., average mass fractions and CSU values, The final results concerning the presence of major, rock-forming elements are illustrated using the spider diagram reproduced in Violin diagrams were chosen for major elements as it permits the visualization of the entire distribution function, together with important statistical parameters, while a box-and-whiskers plot was preferred in the case of trace elements. In both cases, all data were normalized to UCC as one oAs mentioned before, excepting CaO, the average values of the mass fractions of major, rock-forming elements were relatively close to UCC , NASC 2, ABL 2424, and A2, less than 2.5%, suggests an almost uniform origin of sedimentary material from the point of view of siliceous minerals.Silica, which represents the major component of the investigated sediments, presented an average value of 66.86 wt%, almost identical with 66.62 wt% for UCC , and eve2O3 showed an average mass fraction slightly smaller than UCC [2O were shown to be significantly lower than in the case of UCC [2O.At its turn, Althan UCC , NASC [2than UCC , and ABLthan UCC , but higthan UCC . On the e of UCC , NASC [2e of UCC , and ADLe of UCC . Differee of UCC (Table 22O + K2O vs SiO2 (2O/Al2O3 vs. K2O/Al2O3 (2O \u2212 Al2O3 \u2212 Na2O + CaO (K-A-CN) c and SiO2O + CaO d suggest2O + CaO c. It is As shown by the data presented in To detail this analysis, it was necessary to use multiple-sample ANOVA tests. In this regard, the Tukey\u2019s Q test gave a probability equal to one to have the same mean, Kruskal\u2013Wallis gave the same result for medians, and only non-parametric Mann\u2013Whitney and Dunnet post hoc tests evidenceMoreover, it should be pointed out that the investigated area, with a total length of 175 km (about 6.2% of the Danube River length), entirely passes through the Pannonian Plain. All above mentioned findings confirm previous conclusions, according to which, the investigated materials have, regardless of sampling points, the same geochemistry closer to crustal one.Two variants of INAA, Thermal and Epithermal Neutron Analysis, permitted determination of the mass fractions of at least 29 trace elements, including nine lanthanides, the presence of which was detailed discussed in . TherefoTrace elements are important as their distribution permits inferring the nature of depositional material and, in some instances, the anthropogenic influence manifested by an anomalous increase of the mass fraction of some PCE.Concerning trace elements Sc, Zr, La, Th, and U, their presence has almost never been associated with any anthropogenic contamination ,35, whil2 vs. Ni [i,jEF represents the EF of the i-th element corresponding to the j sample, i,jc represents the mass fraction of the i-th element corresponding to the j sample, Sc,jc represents the mass fraction of the Sc corresponding to the j sample, i,UCCc represents the mass fraction of the i-th element in the UCC [Sc,UCCc represents the Sc mass fraction in the UCC [Under these circumstances, we have considered the Enrichment Factor (EF) , as one the UCC , while t the UCC .Sc was chosen as reference element because its presence in not linked to any industrial or human activity.PLI) [EFs:n represents the number of considered PCE for each sample j.To evaluate the global contamination status of the sediments, we have used the Pollution Load Index (PLI) , definedEF \u2265 1, while the sediment could be considered as contaminated if PLI \u2265 1. In both cases, EF and PLI less than one signifies the absence of any anthropogenic contamination. It is worth mentioning that the selection of the UCC as zero contamination reference represents, as mentioned before, a conservative approach. This is not a universal criterion, as in some regions, such as Chaco, Argentina [According to ,44, a PCrgentina ; Hokuetsrgentina ; or the rgentina , the natrgentina one. DepEF for all sampling points, as well as for the considered PCE, i.e., Cr, Ni, Cu, Zn, As and Sb, are reproduced in EF higher than one, which suggests, especially in the case of Sb, a significant degree of contamination. In addition, it should be remarked that antimony, regardless of whether it is an oxic or anoxic substrate, is partially soluble in water [Final results concerning the distribution of in water . Given iPLIs of sedimentary material collected from all other places were within one standard deviation closer, which, according to [On the other hand, excepting the sampling points 1S (confluence of Sava River with the Danube), 5 (Smederovo), and 6M (confluence of Morava River with Danube), and, to a lesser extent, 9P , the rding to , suggestIn our opinion, the increased degree of local contamination as evidenced for sediments collected at the confluence of Sava River with Danube\u20141S, Smderovo\u20145, and at the confluence of Morava River with Danube\u20146M needs a future detailed investigation in context of presumably local PCE sources.Almost all investigated PCE present a certain degree of solubility in water, mainly as organo-metallic compounds, increasing the necessity for a similar investigation of their presence in the Danube River water. This problem is even more important as the Danube catchment basin, to the Serbia\u2013Bulgarian border, covers six countries, some of them among the most industrialized nations in Europe. Therefore, besides sediment contamination, a systematic investigation of Danube water is necessary to evidence any trans-boundary transport of contaminants ,50,51.The mass fraction distribution of nine major, rock-forming elements, Si, Ti, Al, Fe, Mn, Ca, Mg, Na, and K, as well as another 20 trace elements, i.e., Sc, V, Cr, Co, Ni, Cu, Zn, As, Rb, Sr, Zr, Sb, Cs, Ba, La, Hf, Ta, W, Th, and U, were determined by Instrumental Neutron Activation Analysis in 13 samples of shallow, unconsolidated sediments collected along the Eastern Serbian sector of the Danube River, from Belgrade to Iron Gate II dam.As a reference, the mass fractions of the same elements in Upper Continental Crust (UCC), North American Shale Composite (NASC), Average Bottom Load (ABL), and Average Dobrogea Losse (ADL) were used.The distribution of major elements revealed, on one hand, a relative uniformity of their presence, less influenced by the location of sampling points, and a striking similitude to their distribution in all above-mentioned reference systems on the other. This finding appears in good concordance with the location of the Serbian Danube River in the Pannonian Plain, of which sediments represent a mixture of depositional material of different ages from Neoproterozoic\u2013early Paleozoic to Cenozoic and Quaternary.The distribution of incompatible elements, Sc, Zr, La, Hf, and Th, confirmed the crustal origin of sedimentary material, as well as its homogeneity along the entire Eastern Serbian sector of the Danube River.About 30% of the investigated trace elements could be categorized as Presumably Contaminating Elements as their mass fractions exceeded the UCC by 100% in the case of Cr and Ni, 250% for Cu and As, about 300% for Zn, and a maximum of 850% for Sb. These facts were confirmed by the Enrichment Factor and Pollution Load Index, of which, values were systematically much higher than one unit, the threshold for uncontaminated sedimentary material, suggesting the existence of a significant contamination level of the investigated sector of the Danube River.This last inference increases the necessity for a continuous investigation of the Danube River sediment contamination and especially the monitoring of the Danube River water along its path to the Black Sea to evidence the routes of transboundary contamination. In our opinion, such an investigation should be extended to the aquatic flora and fauna, including sturgeons as key indicators for the quality of aquatic environment."} +{"text": "In the published article, there was an error regarding the affiliations for Katarzyna Obarska, Maciej Skorko, and Mateusz Gola. As well as having affiliation 1, they should also have Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland.In the published article, there was an error regarding the affiliations for Alicja A. Binkowska. As well as having affiliation 1, she should also have DrugsTeam, NeuroCognitive Research Center, SWPS University of Social Sciences and Humanities, Warsaw, Poland.In the published article, there was an error regarding the affiliations for Karol Szymczak. As well as having affiliation 1, he should also have Institute of Psychology, The Maria Grzegorzewska University, Warsaw, Poland.In the published article, there was an error regarding the affiliations for Karol Lewczuk. As well as having affiliation 1, he should also have Institute of Psychology, Cardinal Stefan Wyszynski University in Warsaw, Warsaw, Poland.In the published article, there was an error regarding the affiliations for Maria Banaszak. As well as having affiliation 1, she should also have Monar Association, Warsaw, Poland.In the published article, there was an error regarding the affiliations for Bohdan Woronowicz. As well as having affiliation 1, he should also have Consulting Center Akmed, Warsaw, Poland.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in affiliations 3 and 4. Instead of \u201c3. Division of Clinical Research, Department of Medical Research and Division of Medical Oncology, Center for Immuno-oncology, Taipei, Taiwan, 4 Department of Oncology, Taipei Veterans General Hospital and National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan\u201d, it should be \u201c3. Division of Clinical Research, Department of Medical Research and Division of Medical Oncology, Center for Immuno-oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, 4. National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan\u201d.In the published article, an author name was incorrectly written as \u201cSean M.N. Wong\u201d. The correct spelling is \u201cNatalie S.M. Wong\u201d.In the published article, there was an error in the Funding statement. An acknowledgement was missed. The correct Funding statement appears below.This work was supported in part by the Chang Gung Memorial Hospital CMRPG3J0971~3 CORPG3J0251~3. We thank to Zai Lab (Taiwan) Limited for the educational grant to Taiwan Society of Molecular Medicine. The funder Zai Lab (Taiwan) was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In the present paper, we will explore how artificial intelligence (AI) and big data analytics (BDA) can help address clinical public and global health needs in the Global South, leveraging and capitalizing on our experience with the \u201cAfrica-Canada Artificial Intelligence and Data Innovation Consortium\u201d (ACADIC) Project in the Global South, and focusing on the ethical and regulatory challenges we had to face. \u201cClinical public health\u201d can be defined as an interdisciplinary field, at the intersection of clinical medicine and public health, whilst \u201cclinical global health\u201d is the practice of clinical public health with a special focus on health issue management in resource-limited settings and contexts, including the Global South. As such, clinical public and global health represent vital approaches, instrumental in (i) applying a community/population perspective to clinical practice as well as a clinical lens to community/population health, (ii) identifying health needs both at the individual and community/population levels, (iii) systematically addressing the determinants of health, including the social and structural ones, (iv) reaching the goals of population\u2019s health and well-being, especially of socially vulnerable, underserved communities, (v) better coordinating and integrating the delivery of healthcare provisions, (vi) strengthening health promotion, health protection, and health equity, and (vii) closing gender inequality and other (ethnic and socio-economic) disparities and gaps. Clinical public and global health are called to respond to the more pressing healthcare needs and challenges of our contemporary society, for which AI and BDA can help unlock new options and perspectives. In the aftermath of the still ongoing COVID-19 pandemic, the future trend of AI and BDA in the healthcare field will be devoted to building a more healthy, resilient society, able to face several challenges arising from globally networked hyper-risks, including ageing, multimorbidity, chronic disease accumulation, and climate change. In the present paper, we will explore how new technological and digital tools can help address clinical public and global health needs in the Global South ,2, leverACADIC is a newly formed interdisciplinary consortium that brings together a unique multidisciplinary team consisting of clinical public and global health experts, physicists, software engineers, data scientists, biostatisticians, epidemiologists, mathematicians, and biomathematical modelers, from 19 research centers and institutions/organizations, based in several African countries, such as South Africa, Nigeria, Cameroon, Rwanda, Namibia, Botswana, Zimbabwe, Mozambique, and Eswatini, as well as from Canada. The present \u201ccommunication\u201d paper was designed as a narrative literature review followed by a qualitative report of our experience with the ACADIC Project in the Global South, aimed at overviewing the main challenges of contemporary medicine with a \u201cGlobal South\u201d lens to inform the execution of future initiatives in the Global South.Concerning the first part (narrative literature review), we searched PubMed/MEDLINE, a major electronic scholarly database, which represents the most important and commonly utilized biomedical repository. We looked for the following keywords: \u201cGlobal South\u201d, \u201cpublic health\u201d, \u201cglobal health\u201d, \u201cclinical public health\u201d, \u201cclinical global health\u201d, \u201cartificial intelligence\u201d, \u201cbig data\u201d, \u201cbig data analytics\u201d, \u201cInternet of Things\u201d, \u201cdisruptive technologies\u201d, \u201cinnovative technologies\u201d, \u201cdigital tools\u201d, \u201cethical issues\u201d, \u201cethical challenges\u201d, \u201cregulatory issues\u201d, and \u201cregulatory challenges\u201d.Concerning the second part , we carried out a thematic analysis (TA) of the rTo ensure the procedure is adequately carried out, the team initially familiarizes itself with the reports, then, the texts are re-read and coded, subsequently re-examined, re-assessed, and, if necessary, codes are reviewed, and re-analyzed. The coding procedure is assisted by frequency and co-occurrence analyses and the formulation of research questions. New themes can emerge and be identified: if these are considered thematic variations of already identified themes, they are merged and combined, otherwise, they are added to the list of themes. All qualitative analyses were conducted using ATLAS.ti qualitative analysis software . In the following sections, we will briefly overview the main challenges of contemporary medicine with a \u201cGlobal South\u201d lens.Despite the lack of consensus on their precise definitions, health and well-being are not seen anymore as just the absence of disease, illness, or impairment/infirmity/disability, in a narrowly focused way, strictly entailing physical aspects from a mere biomedical context. Health and well-being are, rather, considered as the dynamic outcomes of a complex interplay of several parameters, which encompass various domains, including physical, psychological , and social factors, among others ,5,6. Health and well-being can be investigated from various standpoints and scales, from the individual to the community/population perspectives, along what is known as the \u201chealthcare continuum\u201d. This includes disciplines such as clinical medicine, public and global health, each one of which consists of four major components: namely, (i) prevention by means of disease and disease outbreak monitoring/surveillance and early warning systems (EWSs)\u2014that is to say, the effective collection, integration, interpretation, and deployment of data to enhance and support data-driven monitoring and surveillance of diseases and disease outbreaks, with a focus on systems that can help strengthen preparedness and early response, (ii) identification by means of clinical, public, and global health laboratory innovation\u2014that is to say, an integrated laboratory and facility network, which is equipped with state-of-art infrastructure to provide all primary and specialist diagnostic services needed for disease and disease outbreak care, treatment, and prevention, (iii) individual and community/population health risk management by means of an integrated framework for disease and disease outbreak risk reduction and mitigation, and, finally, (iv) evidence-informed, data-driven decision-making processes ,8,9,10 tWithin the healthcare continuum, given the interrelatedness of the different domains, new specialties are arising. \u201cClinical public health\u201d can be defined as an emerging, cutting-edge, multi-, cross-, and inter-disciplinary field , at the Furthermore, in the last decades, an innovative discipline called \u201cclinical global health\u201d ,18 has eAs such, clinical public and global health represent vital approaches, absolutely instrumental in (i) applying a community/population perspective to clinical practice as well as a clinical lens to community/population health , (ii) idClinical public and global health are called to respond to the more pressing healthcare needs and challenges of our contemporary society Table 2Table 2. In the last decades, health systems worldwide have been facing different, unprecedented challenges, such as the increase in the burden of disease (either communicable or non-communicable), especially in developing countries , mostly The novel Coronavirus (COVID-19) pandemic is just the latest in a series of global disease outbreaks caused by emerging (or re-emerging) infectious diseases (ERIDs), including the H1N1 influenza virus pandemic, the Severe Acute Respiratory Syndrome (SARS), and the West African Ebola epidemics , among oThese outbreaks and, in particular, the still ongoing COVID-19 pandemic have significantly challenged (i) the capacity and ability of healthcare workers to absorb unforeseen health system shocks and external events , (ii) toHealth policies responded with a profound restructuring and reorganization of health systems and medical services to better protect healthcare personnel itself and patients . HoweverTraditional approaches that inform risk assessment and management strategies as well as risk reduction and mitigation efforts aimed at addressing the complex effects of diseases, disease outbreaks, and other public and global public health emergencies assume approximately linear relationships that link from a well-defined source to a single endpoint, and heavily rely on historical data, time series, and observations. Moreover, they are merely reactive, rather than proactive , and focThese approaches have proven to be inadequate for dealing with the challenges presented by the systemic nature of risk and vulnerability, namely, the \u201cmultifaceted interconnectedness of disease outbreaks, poorly understood breadth of population exposure, and profound nuance and detail of vulnerability\u201d . These dAs a consequence, the global community has failed to sufficiently and proactively identify, and respond to secondary impacts that intensify as \u201cglobally networked hyper-risks\u201d generateLearning and adaptation in the short-term response to a disease or an epidemic/pandemic can be enhanced by identifying the capacities and integrating the acute needs of the most vulnerable. Moreover, long-term transformation must incorporate new approaches to disease, pandemic and epidemic prevention, preparedness, management, response, and recovery, to address the systemic nature of risks . Some stMoreover, diseases and disease outbreaks, especially COVID-19, have underlined the need for timely, accurate, and reliable data, to better inform public health decision-making in an evidence-based fashion. As such, data science has played a key role in the response to the still ongoing COVID-19 pandemic, driving measures and shaping interventions to mitigate its burden . An incrBasically, a \u201cfundamental redesign\u201d and a \u201cknowledge and paradigm shift in thinking\u201d with newBy definition, \u201cOne Health\u201d and \u201cplanetary health\u201d/\u201cclinical planetary health\u201d approaches require a system science approach ,65,69 anSince ERID-related challenges, as well as other challenges, including economic-financial, geopolitical, environmental, technological, societal, and health \u201cnetwork hyper-risks\u201d , are gloAI and BDA techniques have developed rapidly over the last 10 years . New tecThe advances in AI , includiIn the last years, scholars have discussed the hypes and hopes of AI- and BDA-based tools and techniques at the individual and community/population levels, in the arena of clinical public and global health, where they can serve as tools to assist public and global health policies and decision-making processes in an informed, evidence-based, data-driven fashion . ConversAs stated by Scoones et al. , currentAI and BDA can help face healthcare needs and challenges, being the catalyst for a profound transformation in the healthcare arena and helpAs such, AI and BDA can affect all four facets of clinical medicine, and public and global health, profoundly reshaping them. AI and BDA can, indeed, (i) help predict communicable/non-communicable disease risk and prognosis, either at the individual and community/population levels , (ii) can enhance and strengthen laboratory functioning and capacity, in terms of identification of innovative biomarkers and precision diagnostics and infectious sample processing , (iii) predict treatment outcomes and monitor and forecast the effectiveness of the package of public and global health interventions implemented , and (iv) predict healthcare utilization (evidence-informed decision-making) . DiffereIn the aftermath of the still ongoing COVID-19 pandemic, the future trend of AI and BDA in the healthcare field will be devoted to building a more healthy, resilient society, able to face several challenges arising from globally networked hyper-risks , includiAll these challenges are highly interconnected. The latter, for instance, is expected, indeed, to profoundly disrupt human health, affecting respiratory and cardiovascular systems, as well as causing injuries and premature deaths and incrSocioeconomic inequalities and risks can exacerbate the effects of climate change itself, whereby sea-level rise and extreme weather events such as flash flooding and storm surges cause widespread devastation to coastal and inland communities across the globe. As urban areas expand, more people living and working near forested areas are likewise affected by greater exposure to disease vectors and longer average wildfire seasons, with catastrophic results .AI- and BDA-based algorithms can help (i) identify climate-change tipping points by means of EWSs, (ii) strengthen the ability to detect such changes, (iii) devise mitigation responses and strategies, and (iv) guide and shape locally-informed policies. In conclusion, the novel use of AI and BDA is anticipated to uncover new links between climate, climate-related disaster exposure, and the burden of disease , helpingThe Global South is a grouping of countries and territories, from South America, Africa, and Asia, that are highly heterogeneous in terms of socioeconomic, cultural, and political characteristics, even though they share (i) obstacles and barriers to access to community and public healthcare services, (ii) the burden of disease generated by communicable disorders, (iii) food and (iv) job insecurity, and (v) the lack of state-of-art resources and infrastructure, necessary for their growth and development . As such, the Global South differs from the concept of the \u201cHemispheric South\u201d, which is a geographical one. The former is, instead, a meta-category or a broad umbrella term that comprises a vast array of decolonized nations, south of the old colonial centers of power. The health needs of the populations dwelling in the Global South are generally overlooked in the scholarly literature and are not prioritized in the political agenda . As previously mentioned, AI and BDA can help pave the way for new opportunities both in the field of preventive and clinical medicine, advancing the design and implementation of personalized treatment and management, as well as precise clinical public and global health interventions. However, despite an accumulating body of evidence, only a few countries from the Global North are leading and shaping research and knowledge in the field, with findings that, as such, may not be generalizable and applicable/directly translatable to the Global South. To be really and truly meaningful, equitable, and impactful, there is an urgent need for socially and ethically responsible, inclusive, and collaborative/participatory AI and BDA, that can drive and support innovation in the Global South, in terms of research, training of qualified personnel, high-quality curated and integrated, diverse and representative, locally relevant and informed databases, algorithms, platforms, and infrastructure.\u201cResponsible\u201d AI and BDA can be defined as an array of innovative and emerging practices of intentionally devising, developing, implementing, and utilizing AI and BDA, to protect the public good and to empower the populations, especially vulnerable, at-risk communities, with a positive impact on society. Responsible AI and BDA are characterized by fairness, inclusiveness, transparency, accountability, explainability, human-centeredness, privacy, and security. \u201cExplainable, trustworthy, responsible AI and BDA for social good\u201d can reduThese risks generated by some AI- and BDA-based technologies require a global governance infrastructure and a set of clear regulatory frameworks aimed at identifying high-risk AI and BDA applications, setting conformity assessments as well as requirements and obligations for AI- and BDA-based system developers, vendors, and users.However, while the Global North is leading the debate on how to build, regulate, and make an \u201cexplainable, trustworthy, responsible use of AI and BDA for social good\u201d , the GloAs previously mentioned, in the present paper, we will explore how AI and BDA can be exploited to address clinical public and global health needs in the Global South, based on our experience with the ACADIC Project in the Global South, focusing on the ethical and regulatory challenges we had to face, and leveraging the framework previously introduced , Table 3ACADIC has been devising and deploying AI- and BDA-based techniques to better understand the impacts of clinical public and global health interventions implemented during the COVID-19 pandemic in the Global South ,90,91,92In South Africa, for example, ACADIC has been piloting the use of AI- and BDA-based modeling ,95,96 toThis has required accounting for country-specific differences in socio-demographic, epidemiological, and clinical variables, including rates of comorbidities. As such, ACADIC has been re-weighting the models initially developed for South Africa ,90. ACADMoreover, in terms of \u201cexplainable, trustworthy, responsible AI and BDA for social good\u201d , ACADIC ACADIC is also devising models that can assist clinical public and global health policy- and decision-makers develop optimal COVID-19 testing policies and mass vaccination strategies as well Through the ACADIC project in the Global South, we have learned various lessons that will inform the execution of future programs and initiatives in the field of clinical public health and AI in the Global South. These lessons point to :Partnering with CLOs and community healthcare workers helped us to acquire some of the data from communities and populations that do not visit the healthcare system. In our partnership with community health workers, we had them visit households in certain communities to collect data for us. Some of the CLOs that we partnered with already have networks set up in some of these communities and this made it very easy for us to acquire some of the \u201chard to get\u201d data. For a meaningful change in the health of people in communities, it is important for solutions to be developed and scaled from the bottom up, as modeling and data collection must be community-focused, -owned, and -co-led . In most of the countries in the Global South, without \u201cbuy-in\u201d from the government, it is difficult to influence policies or implement research results. For policy-driven research in the Global South, this is essential. Buy-in from the decision- and policymakers gave us access to data and the ability to influence the collection of data. Thanks to the fact that we had a seat at the table where decisions were made, we were able to influence data gathering in most of the countries and had it disaggregated/stratified by ethnicity, gender, sexuality, socio-economic class, geographic location, and Indigeneity to better understand how COVID-19 is disproportionately affecting socially vulnerable people. It enabled us to influence government communication strategies to address misinformation about the prevention and treatment of COVID-19.It is essential to put together a team with different expertise. The diverse expertise in our team enabled us to merge new data sources from science, technology, social, and cultural systems, in relation to opportunities and risks, centering local needs and knowledge while learning from all partners\u2019 experiences. Being engaged with communities gave us the ability to adjust swiftly to changing circumstances.For impactful research work in the Global South, it is important to create a network and have each team uniquely assemble its own strategy for meeting the program\u2019s objectives and provide an opportunity for teams to learn from each other and an opportunity for knowledge transfer between the teams. In addition, the teams should be encouraged to draw on their own set of experiences, community partners, local context, constraints, and possibilities. By sharing their processes and results, the groups will draw out larger-scale comparisons, synergies, and conclusions in relation to the overall goal(s). It is important to provide an opportunity for them to \u2018learn by doing and \u2018in the community.\u2019 Research that leads to meaningful change is new in most LMICs in the Global South given the history of colonialism and being \u201cforced by circumstances\u201d to rely on the formal colonial masters up to date for most of the innovations. Thus, it is necessary to hold each other\u2019s hands and provide mutual support. The moment researchers become frustrated with research in most countries, if there is no one to provide them with the necessary support to keep going, they will give up. Learning from each other through weekly meetings, workshops, webinars, town hall meetings, etc., is very essential. We learned from other groups within the ACADIC consortium by having weekly meetings and regular workshops. The transnational partnership\u2019s value-added for all partners in ACADIC is grounded in our sharing across contexts and specific situations regarding effective digital data generation, management, dissemination, and ways to address equity priorities for risk minimization by amplifying the voices and agency of marginalized and highly impacted communities.It is imperative to harness data from all available sources including unconventional sources to make up for the gaps that exist in data. We have used unconventional datasets that include, household visits by community health workers, voice scripts, chatbots, Twitter, Google searches, community-level Reddit, WhatsApp, Facebook, etc., to inform health needs about COVID-19 ,89,91. IWe developed a framework that takes into account regulatory and ethical aspects , as well as community and societal needs. We extensively searched the literature (either scholarly/peer-reviewed) and we iScience granting councils and local funding agencies in the Global South suffer from several, interrelated shortcomings and challenges, including a lack of adequate capacity, coordination, and implementation of research funding policies. Local policy frameworks and enabling structures should be developed and/or strengthened to better support the local communities of scholars and researchers. Moreover, public-private sector partnerships should be incentivized.AI- and BDA-based modeling has attracted increasing interest from policy and decision-makers across countries in the Global South, including Africa. AI- and BDA-based modeling can, indeed, help them shape their local, regional, and national Strategic Plans in an informed, evidence-based, and data-driven fashion, tracking their progress and monitoring their effectiveness. However, there still exists a significant knowledge power imbalance between a few countries leading in AI- and BDA-based modeling and the rest of the world. As such, the AI modeling ecosystem and the research and development (R&D) landscape across the countries in the Global South should be strengthened, in terms of adequate qualified personnel of researchers and innovators, as well as infrastructure and algorithms/tools. In the present paper, we explored how AI and BDA can help address clinical public and global health needs in the Global South, leveraging and capitalizing on our experience with the ACADIC Project in the Global South, and focusing on the ethical and regulatory challenges we had to face.Whilst clinical public health is at the intersection of clinical medicine and public health, clinical global health is the practice of clinical public health in the Global South. As such, clinical public and global health represent vital approaches, instrumental in combining a community/population perspective with clinical practice, identifying health needs, systematically addressing the determinants of health, better coordinating and integrating the delivery of healthcare provisions, reaching the goals of population\u2019s health and well-being, strengthening health promotion, health protection, and health equity, and closing disparities and gaps. Clinical public and global health are called to respond to the more pressing healthcare needs and challenges of our contemporary society, for which AI and BDA can help unlock new options and perspectives. In the aftermath of the still ongoing COVID-19 pandemic, the future trend of AI and BDA in the healthcare field will be devoted to building a more healthy, resilient society, able to face several challenges arising from globally networked hyper-risks, including aging, multimorbidity, chronic disease accumulation, and climate change.Based on the existing literature and our experience, we identified the following lessons (i) strengthening local research and healthcare capacity in the Global South, (ii) strengthening local epidemic/pandemic management planning, including the establishment and development of networks with simulator users in the Global South, (iii) a need for locally informed models in the Global South, (iv) a need for flexible modeling frameworks to respond rapidly to future emergencies in the Global South, (v) limitations and shortcomings of modeling should be communicated clearly and consistently to end users in the Global South, (vi) systematically monitoring the use and implementation of models in the process of decision-making in the Global South, (vii) a need for strengthening AI- and Big Data-related funding in the Global South, and (viii) a need for strengthening AI- and BDA-modeling capacity in the Global South.This is in line with other experiences of authors from the Global South, which reaffirm that equity in health is paramount, being \u201cthe core value of health for all\u201d , as advoAs such, carrying out health research is vital, even though, in some resource-limited areas and environments, it may be particularly complex and difficult, with a limited capacity to undertake and translate research into practice . There, Researchers and scholars from the Global South are terribly under-represented in research ,109,110,The present study has some limitations, that should be acknowledged. The literature review was narrative rather than systematic and the qualitative part of the study was preliminary. As such, further research is needed. Moreover, only a limited number of countries from the Global South could be included and the findings of the current review may not be generalizable to other realities and contexts from the Global South. Through a narrative literature review and our experience with the ACADIC project, we have learned many lessons that will inform the execution of future initiatives in the Global South. If all these lessons are properly addressed, it will be possible to carry out responsible, inclusive, and impactful AI- and BDA-based research in the healthcare sector that will provide global benefits However, our literature review is narrative and our qualitative analysis preliminary. As such, further research in the field is warranted. More in detail, future studies should conduct high-quality systematic reviews on some (sub-)topics such as clinical public and global health, as well as on digital health in the Global South. Moreover, new interactive, web-based trackers and indicators, such as the \u201cGlobal Digital Health Index\u201d (GDHI), should be developed and validated to evaluate and monitor the progress toward inclusive, equitable, responsible, and locally championed AI and digital health throughout the world, with a focus on the Global South."} +{"text": "The smartness that underpins smart cities and societies is defined by our ability to engage with our environments, analyze them, and make decisions, all in a timely manner . We are This Special Issue\u2019s focus is on the IoT, and it is concerned with bringing \u201csmartness\u201d to the IoT and other system layers using technologies such as Cloud, Fog, and Edge Computing; High-Performance Computing (HPC); Big Data; Blockchain; and/or AI. In addition to this Editorial piece, a collection of 13 articles is featured in this Special Issue, covering a range of topics, including mobility, healthcare, image analysis, permeable pavements, solid waste management, sensor node and gateway architectures, air quality monitoring, thermal anomalies and smart helmets in industrial environments, smart airports, smart districts, smart travel choices, sensor cities, artificially intelligent cities, and platform urbanism. Smartness is a multidisciplinary topic and can be defined from different perspectives. We see through the articles included in this Special Issue that smartness can be seen to have four dimensions . These dimensions are: (i) Sensors, IoT, and Data Generation; (ii) Data and Information Processing; (iii) Actuation; and (iv) Digital Systems and Infrastructure. To elaborate, we can see smartness in the way sensing is embedded in a system, the way data and information are processed, how a system interacts internally and with its environment, and whether a system is ubiquitous or limited by space (cloud-based or edge-enabled). What follows is a brief review of the articles included in this Special Issue, which highlights their contributions with respect to these four dimensions. They are grouped according to their application areas: mobility and transportation, healthcare, industrial environments, and other urban infrastructures.Transportation is the backbone of modern economies, albeit at massive human, environmental, and economic costs ,3. Lana Chia et al. use smarAlomari et al. introducMotivated by the fact that over a billion people are disabled worldwide, with 253 million of them being visually impaired or blind, Busaeed et al. propose The detection of anomalies in harsh industrial environments is a challenging task. To address this, Ghazal et al. propose Campero-Jurado et al. discuss Janbi et al. propose,Yigitcanlar et al. investigFeri et al. propose Akram et al. propose Jo et al. examinedThe smartness that underpins smart cities and societies is defined by our ability to engage with our environments, analyze them, and make decisions, all in a timely manner. The IoT has been the focus of this Special Issue, and its concern has been to bring \u201csmartness\u201d to the IoT and other system layers using emerging technologies. The articles included in this issue cover a wide range of applications, including image analysis, permeable pavements, solid waste management, air quality monitoring, thermal anomalies and smart helmets in industrial environments, smart airports, smart districts, and smart travel choices.The field of smartness is exciting, and while a lot has been achieved, the future possibilities with technologies such as Deep Learning, Edge Computing, Virtual Reality, and more are endless. There are many works that are complementary to the research presented in this Special Issue, such as deep journalism , smartiz"} +{"text": "Anxiety is an ambiguous term, meaning an emotional state, a clinical symptom, a disorder, or a group of disorders. Anxiety is a normal feeling that arises when a person believes he is in danger from a threat or unidentified danger, ensuing with a state of alertness, arousal, and exploratory attention. Its distinction from neighbouring concepts, such as anguish, fear, worry, anxiety, panic, or uneasiness, is valuable but controversial.Review and synthesize various contributions from phenomenology and philosophy to the understanding of what it is like to experience generalized anxiety.Selective review of the most prominent literature regarding anxiety psychopathology, namely that of Jaspers, Heidegger, L\u00f3pez-Ibor, Sims, Berrios, Femi Oyebode, Pio Abreu, James Aho, Picazo Zappino and Gerrit Glas.Jaspers described free-float anxiety as common and painful, floating and detached, as a feeling of misunderstood genesis, imposing despite the inapparent object, driving an inescapable need to provide some content to it, but also susceptible to insight by those who experience it. It can take a vitalized or primarily psychic form. Anxiety is closely related to the limits of the human being and to (hopelessness). For Heidegger, angst is the expression of authentic existence. L\u00f3pez-Ibor considered anxiety and anguish nuances of the same experience, in both of which there is fear of the dissolution of the unity and continuity of the self (anguish). When what exists is not a fear, but only a threat, anxiety arises.Phenomenologically informed psychopathology is relevant for clinicians. Complementing neurosciences, each answers questions that the other cannot.No significant relationships."} +{"text": "The International Association for the Study of Pain (IASP) has defined pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, which also comprises a subjective component . Pain isRegarding chronic pain, it entails a serious health burden, and a high comorbidity with other disorders such as anxiety, depression, insomnia, and cognitive impairments ,9,10,11.The principal chronic pain disorders include headache, migraine, and local and generalized musculoskeletal diseases. The last may be further divided into those with inflammatory , mechanical , or unknown origin . These dFibromyalgia, chronic tension-type headache, migraine, and the temporomandibular disorder are some examples of chronic pain disorders without a clear physiological cause. In all of these disorders, the pain intensity is found not to be proportional to the reported injury ,23,24,25The intervention of chronic pain should be considered from a biopsychosocial perspective. As pointed out before, chronic pain is a condition characterized by physiological and biological correlates, in turn modulated by emotions (including negative beliefs) ,33,34,35In general, to contribute to the effectiveness of chronic pain treatment, patients must be informed of the characteristics of the treatment. Thus, they are capable of committing to the treatment and can achieve better results . It is cIn sum, the chronic pain field requires continuous research in order to improve its prevention, diagnosis, and treatment. Considering the worldwide incidence, and prevalence of chronic pain in developing countries , scienti"} +{"text": "IgA nephropathy (IgAN) typically is a slowly progressing disease, with 10% to 60% of patients developing chronic kidney failure within 10 years.In round 1, most statements (19 [95%]) met the criteria for high consensus, including those regarding pathophysiology, diagnosis, and treatment of early stage and rapidly progressive IgAN . ParticiP\u00a0= 0.044). For round 2, statement #28 was split into 2 statements . Further analyses by country can be found in P\u00a0= 0.045). In round 2, the difference in agreement between academic and nonacademic nephrologists for both statements #28A and #28B was no longer statistically significant . It is possible that academic nephrologists may assess the long-term risk-benefit profile of corticosteroids more conservatively than their nonacademic colleagues.Further analyses explored differences in agreement levels among participants practicing in different geographic locations and S2. The DEFINE: Physicians Delphi survey on IgAN identified high consensus overall after just 1 round of the survey. This finding suggests that nephrologists in North America and Europe have similar opinions on IgAN management and that these opinions are largely consistent with the KDIGO guideline. The statement with the lowest level of agreement was statement #28, which described corticosteroid use in adults. Corticosteroids for managing IgAN is a controversial topic, considering recent results from studies including the STOP-IGAN and TESTING trials.The high level of agreement found for the pathophysiology and treatment goal statements ; #3.6Most statements in this survey aligned with the 2021 KDIGO guideline for glomerular diseases.The high levels of agreement found in this study may be driven by the fact that treatment options for IgAN are limited, with no alternatives to consider. However, the treatment landscape of IgAN may change, as many studies are currently investigating potential therapies for this disease.Limitations of this study include that it was conducted in English and did not involve nephrologists from Asia or South America. Furthermore, there was a limited number of female participants and pediatric nephrologists in this survey and S5. In summary, the lowest levels of agreement were observed on corticosteroid use in adult patients who receive optimized supportive therapy but still have elevated proteinuria. Although overall agreement was high regarding this topic, some nephrologists, particularly in Europe, disagreed with the use of corticosteroids in this setting. This suggests that further research on the risk-benefit profile of corticosteroids and new therapies in IgAN are needed. Overall, the DEFINE: Physicians study found high levels of consensus regarding the pathophysiology, diagnosis, management, and monitoring of IgAN among nephrologists from North America and Europe and that, in general, their opinions align with the latest KDIGO guideline for statements evaluated herein.JF is employed by Rheinisch-Westf\u00e4lische Technische Hochschule University of Aachen; has consultancy agreements with Amgen, Bayer, Calliditas, Novo Nordisk, Omeros, Travere Therapeutics, Inc., Vifor, and Visterra; has received honoraria from Amgen, Astellas, Bayer, Calliditas, Novo Nordisk, Omeros, Travere Therapeutics, Inc., Vifor, and Visterra; is a scientific advisor for Calliditas, Omeros, and Travere Therapeutics, Inc.; and is on the speakers bureau for Amgen and Vifor. JB has received research grants from Argenx, Calliditas, Chinook Therapeutics, Galapagos, GSK, Novartis, Travere Therapeutics, Inc., and Vera Therapeutics; and serves as a medical/scientific advisor to Alnylam Pharmaceuticals, Argenx, Astellas, Biocryst, Calliditas, Chinook Therapeutics, Dimerix, Galapagos, GlaxoSmithKline, Novartis, Omeros, Travere Therapeutics, Inc., UCB, Vera Therapeutics, and Visterra. RC has consultancy agreements with Amgen, Argenx, Calliditas, Novartis, Ostuka, Reata, Recordati, and Travere Therapeutics, Inc., and has an agreement with UpToDate. RL has received research funding from Calliditas, Chinook, National Institutes of Health, Novartis, Travere Therapeutics, Inc., Pfizer, Vera, Omeros, and Visterra; and is an advisor for Alexion, Calliditas, Chemocentryx, Chinook, Novartis Omeros, Pfizer, Reatta, Travere Therapeutics, Inc., and Visterra. JR has received research grants from Travere Therapeutics, Inc.; is on a steering committee for Travere Therapeutics, Inc.; and has consulting/advisory board roles with Angion Biomedica and Travere Therapeutics, Inc. HNR has received consulting fees from Calliditas, Chinook, Novartis, and Travere Therapeutics, Inc.; has received honoraria from Novartis; is an advisor for Novartis and Travere Therapeutics, Inc.; has served as national coordinating investigator for trials by Calliditas and Chinook; has served as an investigator for GN clinical trials by Alnylam, Calliditas, Chemocentryx, Omeros, and Pfizer; and is director of the Glomerulonephritis Fellowship funded by the Louise Fast Foundation. BR has received consulting fees from Calliditas, Novartis, Omeros, and Travere Therapeutics, Inc. DTS has consultancy agreements with BioPorto and Travere Therapeutics, Inc. MV is on advisory boards for Apellis, Novartis, Roche, and Travere Therapeutics, Inc.; receives consulting fees from Alexion; and has participated in studies sponsored by Bayer, Novartis, Chemocentrix, and Chinook. This does not influence the content of the present study. CP is employed by ApotheCom, which received funding support from Travere Therapeutics, Inc. for the DEFINE: Physicians study. VT has served as principal investigator and steering committee member for clinical studies in focal segmental glomerulosclerosis supported by Travere Therapeutics, Inc., and has consultancy agreements with AstraZeneca, Boehringer Ingelheim, Calliditas, Novartis, Omeros, and Travere Therapeutics, Inc."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China\u201d, it should be \u201cDepartment of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China\u201d.In the published article, there was an error in affiliation 2. Instead of \u201cDepartment of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China\u201d, it should be \u201cState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China\u201d.In the published article, there was an error regarding the affiliation for Ruiying Han. As well as having affiliation 2, they should also have Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.In the published article, there was an error. There was a mistake in the time range of the searched literature in Abstract.Methods, 1. This sentence previously stated:A correction has been made to Abstract, \u201cWe systematically searched databases including Medline, Embase, and Web of Science for studies up to March 2022 with no start date limited.\u201dThe corrected sentence appears below:\u201cWe systematically searched databases including Medline, Embase, and Web of Science for studies from January 2000 to March 2022.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Life.Hypoxia is a current research topic in biology, physiology, and medicine. The effects of hypoxia and the adaptive and maladaptive responses to the hypoxic stress are extensively explored in the domains of altitude, exercise, pulmonary and cardiovascular medicine, inflammation, immunity, cancer, and metabolic diseases. However, the molecular machinery that regulates the activity of certain genes in response to hypoxia is still not explored. This Special Issue \u201cCellular and Functional Response to Hypoxia\u201d presents 14 papers dealing with all aspects of responses to hypoxia, at the molecular, cellular, and integrative levels ,3. First"} +{"text": "There is an error in affiliation 5 for author Verena Loidl. The correct affiliation is: Institute for Medical Information Processing, Biometry, and Epidemiology\u2014IBE, LMU Munich, Munich, Germany."} +{"text": "Instead of \u201cDepartment of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary\u201d, it should be \u201cDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary\u201d.In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Background: Health organisations and stakeholders use social media for a range of functions, including engaging stakeholders in the design and quality improvement (QI) of services. Social media may help overcome some of the limitations of traditional stakeholder engagement methods. This scoping review explores the benefits, risks, barriers and enablers for using social media as a tool for stakeholder engagement in health service design and QI. Methods: The searches were conducted on 16 August 2022. Inclusion criteria were: studies of any health service stakeholders, in any health setting, where social media was used as a tool for service design or QI. Data was analysed using deductive content analysis. A committee of stakeholders provided input on research questions, data analysis and key findings. Results: 61 studies were included. Benefits included improved organisational communication and relationship building. Risks/limitations included low quality of engagement and harms to users. Limited access and familiarity with social media were frequently reported barriers. Making discussions safe and facilitating access were common enablers. Conclusion: The benefits, risks, barriers and enablers identified highlight the complexity of social media as an engagement tool for health service design and QI. Understanding these experiences may help implementers design more effective social media-based engagement activities. Social media has shaped the internet since Web 2.0 was defined in 2004 . Social Social media can also be used to facilitate the engagement consumers and other stakeholders in activities to change, design, or improve health services . BataldeStakeholder engagement in health service design and QI which includes consumers has been shown to improve patient access and outcomes ,16,17, aThe aim of this scoping review was to explore the benefits, risks, barriers and enablers for using social media as a tool for stakeholder engagement in health service design and/or QI. This study complements a previously published paper which used the same scoping review method and described a related but distinct set of findings on the features of social media platforms, models of communication, populations of people, and types of service design, QI or change activities . The keyThis scoping review was conducted using Joanna Briggs Institute (JBI) methodology . The objIt should be noted that the JBI methodology for scoping reviews was updated in 2020 however this was after the scoping review protocol was published and enacThis review was guided by the involvement of an advisory committee of three healthcare consumers and three healthcare service providers. Members of the advisory had professional and/or lived experience in palliative care, mental health, ICU and critical care, transplantation, chronic disease, consumer engagement and representation, and health communications.The advisory committee and scoping review were part of a larger doctoral research project. Committee members were invited following purposeful sampling from theDeciding upon the research question;Finding articles for screening;Assisting with data analysis, including making suggestions to refine and re-group codes and themes;Reviewing the manuscript; andShaping the content of the discussion section through prioritising the analysis findings based on their own experience of the health system.Advisory committee members contributed to the review by:Advisory committee member contributions to the review were made through two 90 min meetings held via video conference, and through ongoing email correspondence throughout the review and manuscript-writing process.The two members of the advisory committee who provided feedback on the manuscript, and answered the questions which informed the discussion section, are included as co-authors on the review .The eligibility criteria outlined below and the subsequent search strategy and methods for the extraction of the results were guided by the Population-Concept-Context structure . The eliUsers or potential users of a health service ; and/orHealth service providers .For inclusion in this review, participants in the included studies were:No restrictions were placed on the age or gender of study participants.Studies only involving participants from non-health service settings were excluded from the review.Studies where social media was used as a tool within design or QI activities which were initiated by health organisations, andStudies where social media was used as a tool by stakeholders to influence or advocate for changes to the design or delivery of health services, systems or policy.The core concept to be examined in this review are the benefits, risks, barriers and enablers of using social media as a tool for health service design and QI. To capture the full range of potential uses of social media in health service design and QI, two broad study types were included. These were:A date range limitation of \u20182004\u2013current\u2019 was placed on the search. This date range was chosen because 2004 is considered the beginning of Web 2.0, the era in which the internet shifted from being primarily comprised of static webpages, to instead being made up of sites and applications which allowed for user-generated content creation and distribution . This shStudies where social media was used, but there was no intention or objective to design or improve health services, systems or policies were excluded from the review. This included social media being used for disease surveillance, health information dissemination, treatment, peer support, education and research without health service change, design or improvement.Studies conducted in health service or health policy settings and published in English. Studies from any geographic location, regardless of income status, were included.Studies conducted in non-healthcare settings were excluded.Original primary research or evaluation articles (any methods) in peer reviewed academic publications, were eligible for inclusion in the review. Sources without original research, and secondary research literature, were excluded from the review.On 16 August 2022 Medline OVID, Embase OVID, PsycINFO OVID, and CINAHL EBSCO were searched. All searches were restricted by the date range of January 2004\u2013current (16 August 2022) and published in English only. Example search strategies for Medline OVID and Embase OVID are provided in Supplementary Table S2.In addition to the searches above, the reference lists of included studies were screened for potentially eligible studies. Members of the advisory committee also submitted potentially relevant studies for inclusion.L.W. screened the titles and abstracts of retrieved studies, and the screening process was managed in EndNote. L.W. retrieved the full text of potentially eligible studies and assessed them for inclusion, using a screening template developed by L.W., N.H. and S.H. . When anThe analysis represents the scoping review step of \u201ccharting the data\u201d which allows for both a numerical summary of the scope of the literature in terms of quantity of research and qualComments from the advisory committee in response to the results of the data analysis also informed the content of the discussion section of this article, including how results should be presented and which elements should be emphasised.In the protocol and the When an otherwise eligible conference abstract was identified, an additional search was conducted to determine whether a peer reviewed article from the same study had been published. When an otherwise eligible secondary research article was identified, the studies included in the review were individually screened for eligibility.After screening 5456 titles and abstracts, and 292 full text articles, 61 articles from 59 study settings were included in the scoping review. All articles were published since 2010, with 23 of the included articles (38%) published since 2020. The majority of studies (90%) were conducted in high income countries. The list of included studies and their key characteristics are shown in The benefits, risks, barriers and enablers for the use of social media as a tool for stakeholder engagement in service design and QI are presented below. Key findings of the analysis are presented in the commentary for each of the a priori themes. A summary of the themes, sub-themes and codes developed through the analysis is presented in Using social media for stakeholder engagement in health service design and QI resulted in a broad range of reported benefits. Benefits were grouped into the sub-themes of (1) improves organisational communication, (2) builds relationships, (3) higher quality information and (4) improves organisational culture and reputation.Improves the efficiency of communication. The most common benefit relating to organisational communication was that using social media as a tool within health service design and QI activities improves the efficiency of communication [nication ,87,92,95nication ,73,82,92nication ,85,86,92nication ,71,80,95nication ,55,66,71nication ,69,73,84nication ,52,68 anAdditional channel for communication. Social media provides an additional channel for communication [nication ,73,80,84nication ,58,80,84nication ,56,65,66nication ,59,73. NFacilitates collaborative relationships. Social media is beneficial for collaborative relationship building between individuals, groups or organisations [isations ,89,91,93isations ,86,89,91isations ,48,70, sisations ,77,86, aisations ,91,93.Engages new audiences. Using social media in health service design and QI also provides opportunities to develop relationships with new audiences [udiences ,86,88,91udiences ,59,73 anudiences .Improves clinical practice. The relationship-building capacity of social media was also seen to improve clinical practice [practice ,81,91,97practice ,91,97, apractice ,72,81.Improves the quality of information gathered or shared. Social media was seen to improve the quality of information gathered or shared by organisations [isations ,86,90,95isations ,69,73,85isations . In the isations ,84,90,95Facilitates high quality discussions. Social media was seen as effective for facilitating high quality discussions [cussions ,67,69,76cussions ,56, creacussions ,67,69, aFacilitates positive organisational culture change. The use of social media in QI and service design was seen to facilitate positive organisational change [l change ,82,84,92l change ,69,74,84l change ,71,81,92l change ,52, incrl change ,52,81,84The risk and limitations reported in the included studies were grouped into the sub-themes of (1) limited or ineffective engagement, (2) limited evidence of effectiveness, (3) risks of direct harm to individuals and organisations, and (4) challenges to strategic use.Underutilisation by target audiences. The most frequently reported risk or limitation theme was that social media is underutilised by target audiences of the health service or QI/design activity [activity ,90,96,97activity ,86,90,97activity ,52,65,74activity ,96,97, pactivity ,97 and sactivity observedactivity found thQuality of discussion or information gathered not sufficient for QI purposes. The quality of discussion or information on social media could limit its effectiveness for informing QI activities [tivities ,76,80,97tivities ,65,76,97tivities ,57, and tivities ,63,75,80Unclear evidence of the benefits compared to traditional stakeholder engagement methods was a limitation to using social media in some of the included studies [ studies ,80,84,86 studies ,55, one studies and one studies . There a studies ,55,81,86Malicious, fake or negative messages and actions were recognised as a risk [s a risk ,86,90,97s a risk ,86,90,97s a risk were exas a risk ,60,64,90s a risk .Breaches of privacy and professional behaviour. Privacy and professional behaviour breaches are a concern for all social media users engaged in service design and QI [n and QI ,74,76,84n and QI ,41,84. Sn and QI and are Difficult to use strategically to achieve change. Social media can be difficult to use in a strategic way to achieve change [e change ,63,81,97e change ,63. AddiDifficult to evaluate. Social media engagement was seen as difficult to evaluate in five studies [ studies ,65,74,80 studies were allBarriers to social media use in health service and system design and QI were experienced by all user types. Barriers included specific, observed, barriers which occurred during a study, and expressed concerns based on opinions or beliefs about health service use of social media that were significant enough to stop or limit social media use. The expressed concerns that act as barriers to the use of social media were wide-ranging and were most often expressed by organisations or service providers, rather than health consumers. The barriers identified in the included studies have been grouped into the sub-themes of (1) lack of access to and familiarity with social media, (2) lack of organisational processes and support, (3) concerns about how people behave online, and (4) problems with social media platforms.Lack of resources and access was the most frequently occurring barrier [ barrier ,86,96,97 barrier ,86,96,97 barrier ,58,82,97 barrier and staf barrier .A lack of skills and confidence in using social media [lack of familiarity with using social media for health or QI purposes [al media ,74,84,97purposes ,68,72,88Issues with organisational culture and a lack of executive support were observed as barriers in some studies [ studies ,71,72,84 studies ,52,61,72 studies ,43, gove studies ,43, a la studies ,84, and studies ,71. From studies ,52.Concerns about implementation and evaluation processes were expressed as barriers to the use of social media [al media ,52,65,73al media ,50,51,52al media ,65.Concerns about how to manage messaging, people and interactions in a public forum were reported as barriers [barriers ,68,72,97barriers ,66 or fibarriers , other ubarriers , legal abarriers , managinbarriers , and worbarriers ,52,97.Concerns about the possibility of users breaching privacy or professional codes of behaviour were expressed as barriers to using social media for health service design and QI activities [tivities ,74,91,97Unwillingness to share personal information online can act as a barrier to consumers using social media for health service design and QI activities [tivities ,89,91,97Rapid changes in the social media environment meant organisations struggled to maintain a presence across all relevant platforms [latforms ,89.Poor usability of platforms, particularly purpose-built platforms [latforms or platflatforms , were alThe enablers of social media use in health service or system design and QI were grouped into the sub-themes of (1) facilitating access and use for all stakeholders, (2) making discussions safe, (3) providing high quality content and user incentives, (4) supportive organisational systems and culture, and (5) building a social media community.Making use of social media easier for target audiences. Making social media easier to use enables its use in health service design and QI activities [tivities ,92,96,97tivities ,69,73,81tivities ,66,77,87tivities ,86 also Organisational systems, processes, resourcing and partnership. Organisations can enable the use of social media through creating systems, processes, plans and roles related to social media use [edia use ,87,93,97edia use ,74,97, aedia use ,81,82,87edia use ,52, and edia use ,73 and sedia use ,43,73,82Providing multiple ways to engage. Social media being only part of a suite of engagement strategies was an enabler [ enabler ,80,85,88 enabler ,69,73.Facilitating access to social media. Making access to social media easier enabled its use [ its use ,73,77,93 its use ,73. Advo its use ,73, or eMaking discussions safe. Safe discussions for all participants was a commonly reported enabler [ enabler ,84,91,93 enabler ,72,73,84 enabler ,65,69,93 enabler ,69. Ther enabler ,69,71,91Delivering engaging, trustworthy and targeted content. Quality content, tailored to social media platform formats and communication styles, is a way to enable and encourage use of social media for health service design and QI [n and QI ,86,88,94Users gaining benefits from participation. All user types were more likely to use social media if they could see benefit from their participation [cipation ,73,81,82cipation ,41,81, scipation ,81,82, acipation , seeing cipation ,81,82, acipation ,73,81,82Fostering connections between users within a social media community. Connections between users enabled the use of social media [al media ,88,89,93al media ,68,88,89al media ,40,72,82al media ,82,93. DOrganisations promoting their use of social media. Promotion is a way to build a social media community for health service design and QI activities [tivities ,51,52,65The findings of this review present a comprehensive summary of the scope of existing research into the risks, benefits, barriers and enablers of social media use experienced by stakeholders involved in, or trying to advocate for, the design and improvement of health services, systems and policy.Benefits of social media use in health service and system design and QI included improvements in organisational communication, culture and reputation, and improvements in relationships and the resulting quality of information from the social media process. The most frequently reported enablers were approaches which made access and use easier and discussions safer. Common negative experiences of use related to the risks of limited engagement and a lack of evidence around social media. In terms of barriers, a lack of access to, and familiarity with, social media, and a lack of organisational support were reported most frequently.In general, the benefits, risks, barriers and enablers of social media use described in the current literature were similar across user groups, which indicates that solutions to overcome reported risks and barriers are likely to benefit all users. However, further study into the experiences of marginalised population groups is warranted and might reveal different experiences that are not currently known.Advisory committee members determined the most relevant and important findings from the analysis, based on their experience of stakeholder engagement in health service design and QI and their knowledge around the issues related to social media-based engagement faced by health services and their stakeholders. These findings are emphasised and discussed in detail in the sections below.Social media may assist in helping health services engage new audiences in the process of QI ,86,88,91The risk of negative, false or malicious messaging was highlighted as an important finding, even though this risk was only mentioned in thirteen studies ,86,90,97The advisory committee felt that the strategies of monitoring ,72,73,84Whatever the reason for the potential under-reporting of monitoring, moderation and group rules, the fact that our advisory committee highlighted the importance of these strategies indicates that they may be a key area for future research, in order to better understand the impacts of monitoring and moderation practices on stakeholder engagement in health service and system design and QI.Social media can have positive impacts on trust and the quality of relationships between consumers and their providers or health organisations. The potential for social media use to make organisations more transparent ,69,74,84However, the findings of the review also demonstrate that this experience of improved relationships is not universal. Some of the included studies identify risks of negative experiences for users through social media messaging or online behaviour ,86,90,97There was some discrepancy between consumers wanting some ability to maintain privacy and anonymity in social media spaces ,91, and This is the first scoping review to our knowledge to explore risks, benefits, barriers and enablers for using social media as a tool within health service design and QI activities. Much of the existing literature which examines social media use in health either discusses theoretical models of use in service design or QI activities ,107,108,The findings of this review challenges previous theoretical literature on the use of social media in health service design and QI. Much of the theoretical literature views social media as a way to overcome some of the limitations or barriers of traditional face-to-face models of consumer engagement ,24,25,26Additionally, the findings of the review reinforce what is known around the use of social media in health more broadly, such as the benefits of improved data gathering and sharing, improved relationships and support, and concerns about privacy, usability and misinformation, which are already reported in research on social media-based health peer support and health service delivery activities ,7,8.Few included studies reported monitoring and moderation as an enabler. It may be under-reported because moderation is simply seen as usual business by the organisations and groups that manage social media, and so the use of moderators was not explicitly stated. Given that moderation has the potential to mitigate some of the risks and barriers of social media use , but may also create or reinforce power structures in online spaces which can affect the quality of engagement , more atThere were mixed findings on some key issues. For example, some studies found social media use improved the richness and authenticity of the information gathered for QI and service design organisations ,86,90,95The objectives and inclusion criteria for this review meant that the views, opinions and experiences of people who are not current social media users, but who are involved (or who could be involved) in health service design or QI through other engagement methods, were most likely not captured in the included studies. By not including this group, key experiences may have been missed, particularly ones relevant to increasing social media uptake by non- or infrequent-user groups, or understanding experiences that may lead to stakeholders not engaging through social media at all. Additionally, the included studies largely reported on the process of social media-based engagement methods, rather than outcomes of social media-based engagement, or comparisons between social media engagement methods and more typical engagement methods. This means that the findings of the included studies may reflect some pro-social media bias, as they were conducted in organisations or with stakeholders who had already decided to use social media as an engagement tool.This review had some methodological limitations. The review protocol was published and reviews guided by an earlier version of the JBI Reviewer\u2019s Manual using a Finally, using a deductive content analysis method with a priori themes as a coding framework, may have led us to overlooking opportunities to expand or refute existing theories . To miniThis review adds to the growing empirical literature on the use of social media for consumer engagement in health service design and QI, as well as potentially for broader engagement purposes. Health services and stakeholders involved in design or QI activities could use the findings to inform their planning. For example, the findings relating to benefits may provide support for social media as an engagement approach, while the enablers give practical strategies for implementing social media as a stakeholder engagement tool. The risks/limitations and barriers findings may help planners understand where they need to provide support to help people engage or may meet resistance to social media engagement approaches.This review has uncovered a number of potential areas for future research. The highly dynamic nature of social media makes it likely that new issues and experiences around the use of social media as an engagement tool in health service design and QI will emerge in the future. Future research could examine innovations in social media-based engagement and how new risks and barriers to use could be overcome. In particular, the increase in health services being provided digitally and/or remotely during the COVID-19 pandemic may leadWhile studies in this review described benefits around involving new people in engagement activities ,86,88,91This review has also identified potential under-reporting of monitoring and moderation as an enabler for stakeholder engagement through social media. Further research into the role and impacts of monitoring and moderation of health-related social media spaces may lead to a better understanding of the role social media moderators play in facilitating stakeholder engagement in health service design and QI.This scoping review examined the risks, benefits, barriers and enablers when using social media as a tool to engage a range of stakeholders in health service design or QI activities. The benefits, risks, barriers and enablers described in the included studies highlighted the complex experiences of individuals and health service engaging in service design or improvement through social media. Social media may improve organisational communication and help individuals build relationships which can enhance health service design and QI activities, but can also expose health services and individuals to reputational risks, trolling, harassment and breaches in privacy. These risks can be managed through strategies such as monitoring and moderation of social media spaces and establishing organisational policies and processes around social media. However, without executive support and good communication between implementing teams, concerns about these risks can become barriers to using social media as stakeholder engagement tool, particularly in health services with an existing culture of risk aversion. In addition to these potential barriers caused by organizational culture, health services using social media in their suite of engagement strategies need to consider whether there are any accessibility and usability barriers in any of their stakeholder groups, including access to internet, access to computers and other devices, and the usability or accessibility of social media platforms.Having a good understanding of the complexity of using social media as a stakeholder engagement tool in the design and improvement of health services may assist planners and implementers to be more aware of, and more able to overcome, some of the known barriers, risks and limitations. It is also important for implementers to understand that there may be experiences that are not yet captured, due to the dynamic social media environment and lack of data on the experience of marginalised groups."} +{"text": "Around 1,000 peer-reviewed papers were selected from 3,450 articles published during 2020\u20132021, and reviewed as the representative advances in tribology research worldwide. The survey highlights the development in lubrication, wear and surface engineering, biotribology, high temperature tribology, and computational tribology, providing a show window of the achievements of recent fundamental and application researches in the field of tribology."} +{"text": "Due to a production error, there was an error in affiliation 1. Instead of \u201cArtificial Life Lab, Institute of Biology, University of Graz, Prague, Austria\u201d, it should be \u201cArtificial Life Lab, Institute of Biology, University of Graz, Graz, Austria\u201d.The publisher apologizes for this mistake. The original version of this article has been updated."} +{"text": "In 2018, ~382,000 new cases of cancer and 157,400 related deaths were registered in France on overall health. It is an essential and key parameter for the prevention and treatment of chronic diseases, such as cancer. PA is defined as any body movement generated by the contraction of skeletal muscle that raises energy expenditure above the resting metabolic rate and is characterized by its modality, frequency, intensity, duration, or context of practice . It is cWhile PAL has long been studied for its role in non-communicable diseases , the impvs. \u201cSB\u201d or \u201chigh\u201d vs. \u201clow\u201d PA to describe the complexity of human movement behaviors. Indeed, we and other researchers encourage a move toward a multidimensional approach to PA characterization, and a detailed analysis of body motion and fine movement behaviors to identify more precisely individuals at risk for future chronic disease . Thus, pry only) , and recry only) . CommercGE, DT, and MD conceived the idea, drafted, revised, and edited the manuscript. LD, AR, QJ, and FM revised the manuscript. All authors read and approved the final version of the article."} +{"text": "In \u201cShare to Seek: The Effects of Disease Complexity on Health Information\u2013Seeking Behavior\u201d :e21642), the authors noted two errors.In the originally published article, affiliations of the first author, Ashwag Alasmari, appeared in the following order:1,2Ashwag Alasmari1University of Maryland, Baltimore County, Baltimore, MD, United States2King Khalid University, Abha, Saudi ArabiaMoreover, the original Affiliation 2 inadvertently did not specify any department.In the corrected version, affiliations appear in the following order, and the reordered Affiliation 1 specifies the author's affiliated department:1,2Ashwag Alasmari1Computer Science Department, King Khalid University, Abha, Saudi Arabia2University of Maryland, Baltimore County, Baltimore, MD, United StatesThe correction will appear in the online version of the paper on the JMIR Publications website on September 30, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Psidium cattleianum), cambu\u00ed (Myrciaria floribunda), gabiroba (Campomanesia xanthocarpa), jabuticaba (Plinia cauliflora), and jambolan (Syzygium cumini). Scientific studies were gathered and selected in Google Scholar, Scielo, and Science Direct indexed databases, out of which 14 were about ara\u00e7\u00e1, 7 concerned cambu\u00ed, 4 were about gabiroba, 29 were related to jabuticaba, and 33 concerned jambolan, when we observed the pre-established inclusion criteria. Results showed that the anthocyanins, such as cyanidin, petunidin, malvidin, and delphinidin, were the mostly identified class of flavonoids in plants of the Myrtaceae family, mainly relating to the purple/reddish color of the evaluated fruits. Other compounds, such as catechin, epicatechin, quercetin, and rutin were also identified in different constituent fractions, such as leaves, peel, pulp, seeds, and in developed products, such as jams, desserts, wines, teas, and other beverages. It is also worth noting the positive health effects verified in these studies, such as anti-inflammatory qualities for jambolan, antidiabetic qualities for gabiroba, antioxidant qualities for ara\u00e7\u00e1, and cardioprotective actions for jabuticaba, which are related to the presence of these phytochemicals. Therefore, it is possible to point out that flavonoids are important compounds in the chemical constitution of the studied plants of the Myrtaceae family, with promising potential in the development of new products by the food, chemical, and pharmaceutical industries due to their bioactive properties.This integrative review aims to identify the main flavonoids present in some species of the Myrtaceae family. Studies published between 2016 and 2022 were selected, specifically those which were fully available and written in Portuguese, English, or Spanish, and which were related to the fruits ara\u00e7\u00e1 ( Eucalyptus spp.), used in the production of wood and flavoring agents [Psidium cattleianum Sabine) [Myrciaria floribunda (H. West ex Willd.) O. Berg) [Campomanesia xanthocarpa (Mart.) O. Berg) [Syzygium cumini (L.) Skeels) [Plinia cauliflora (Mart.) Kausel) [Myrtaceae is a family comprising 121 genera and 5800 plant species, occurring mainly in tropical and subtropical regions of the world, being a predominant group in the Brazilian Atlantic Forest [ Sabine) , cambuizO. Berg) , gabirob Skeels) , and jab Kausel) , studiedVarious species of the Myrtaceae family, when processed, provide important products, such as essential oils, dyes, and food products, and can be also employed in traditional medicine ,9,10,11.The range of utilities provided by these plants may be related to the presence of phytochemicals, such as flavonoids, which are the main compounds of interest in this study. These compounds help in the prevention of various chronic non-communicable diseases, such as cardiovascular pathologies, oxidative stress, certain types of cancers, atherosclerosis, diabetes, Alzheimer\u2019s disease, cataracts, and other respiratory disorders, and are concentrated in different parts of the plant . FlavonoPsidium, Myrciaria, Campomanesia, Plinia, and Syzygium stand out for their phytochemical composition with a multitude of bioactive compounds, characterized by the production of flavonoids, water-soluble and condensed tannins, saponins, mono- and sesquiterpenes, and triterpenoids, among others [In this context, fruit trees of the genera g others .Psidium originates from tropical and subtropical America, which has great biological and economic importance in Brazil. This group includes several species of trees and shrubs, with emphasis on the guava tree (Psidium guajava L.) and ara\u00e7\u00e1 tree (P. cattleianum), plants geographically distributed in several regions of Brazil [The genus f Brazil .Popularly, the fruits of the ara\u00e7\u00e1 tree are known as ara\u00e7\u00e1, yellow ara\u00e7\u00e1, red ara\u00e7\u00e1, ara\u00e7\u00e1-de-comer, ara\u00e7\u00e1-da-praia, ara\u00e7\u00e1-de-coroa, and ara\u00e7\u00e1-do-mato. Despite the distinction of names, varieties and color, the fruits are characterized by having an ovoid shape, translucent pulp, and a kernel full of seeds, which can vary from approximately 22 to 250 units 16,17,1,117,18.Ara\u00e7\u00e1 has high agro-food potential due to its chemical composition. Among the compounds found in this fruit, organic acids, carotenoids, and flavonoids stand out . In termFood technology allows the incorporation of ara\u00e7\u00e1 into a multitude of products in order to make it available on the market, and it is found in the form of sweets, jams, and flour, benefiting producers and adding economic value to certain communities . In scieMyrciaria, the cambu\u00ed tree is a medium-sized tree (with a height of 6\u201314 m) and a rounded crown, distributed throughout the northeast and north of South and Central America. Its fruits are characterized by being shiny, fleshy, and juicy elliptical berries, which can have a diverse color, ranging from orange to dark purple . Additionally, they are fruits that have antioxidant compounds in their constitution, especially carotenoids and flavonoids [Cambu\u00ed presents a succulent pulp, a sweet and astringent flavor, and is characterized by having high concentrations of sugars and excellent levels of vitamin C , with a varied, dense crown and a smooth reddish-yellow stem . Its fruJabuticaba has high mineral concentrations, such as iron, copper, and manganese, as well as vitamin C; however, it stands out in the research scenario for its significant concentration of phenolic compounds, mainly anthocyanins, which are concentrated mainly in its peel, which is usually discarded and sees little use industrially .According to Batista et al. , consumpPsidium cattleianum, Myrciaria floribunda, Campomanesia xanthocarpa, Plinia cauliflora, and Syzygium cumini.Considering the large number of species of the Myrtaceae family and their importance, it is evident that there is still much to be studied, especially in relation to their chemical constituents. Therefore, the objective of this study was to carry out an integrative review identifying the main flavonoids present in Through the search strategies, 2516 scientific works were identified in the aforementioned databases, with the selection process shown in Out of these studies, 2358 were excluded by the previous analysis of the title and abstract since they did not answer the guiding question or were found to be duplicated in different research bases. After a complete reading of 158 works, 87 articles published between 2016 and 2022 were selected to compose this integrative review, with an emphasis on the phytochemical characterization of vegetables, beneficial effects on human health, and product development with the maintenance of bioactive compounds.n = 11), in 2021 , in 2020 , in 2019 , in 2018 , in 2017 , and in 2016 .As shown in Bioactive compounds or phytochemicals are substances derived from the secondary metabolism of plants, with beneficial properties for human health . FlavonoFor the identification and/or quantification of these bioactive constituents in the different extracts evaluated, the following methods were employed: spectrophotometry , LC-DAD-Catechin and quercetin were the prominent flavonoids in the evaluation of the leaves of the five species studied in this work, and these compounds were identified by Balyan and Sarkar and BalyO-glucoside), quercitrin (quercetin-3-O--L-rhamnoside), and rutin (quercetin-3-O-rutinoside). All of these compounds are found in extracts of cambu\u00ed and gabiroba leaves [Quercetin is an aglycone, which can be found in the glycosylated form bound to different sugars; some examples are isoquercitrin , apigenin (flavone), taxifolin (flavanone), and isorhamnetin 3-O-glucoside (flavonol) were other flavonoids identified in the extracts of the studied fruits, both whole, dried, or lyophilized. Pulps, commonly used in product development, were characterized by Garcia et al. [Plantagoside (flavanone), hesperetin 7-a et al. when evaa et al. when stua et al. when anaa et al. when stuDiets rich in industrialized, refined products, high in sugar, fat, and lacking in vegetables are one of the main risk factors for the populations\u2019 health, since they are associated with delicate health conditions, favoring cardiovascular diseases, diabetes, stroke, obesity, and certain types of cancers, among others . As suchInsulin resistance (IR) may be a risk factor for the development of cardiovascular disease and steatosis, which is associated with abdominal obesity, type 2 diabetes, and other syndromes. This pathology may contribute to increased oxidative stress and damage to cell membranes and other functional components, such as proteins and lipids .Due to these issues, Cardoso et al. evaluateP. guajava and P. cattleianum leaf extracts and their nano-liposomes in improving paracetamol-induced hepatotoxicity in rats.In addition to the properties of ara\u00e7\u00e1, Vinholes et al. concludeRegginato et al. evaluateThe antigenotoxic potential of jabuticaba peel extracts was investigated in the work by Marques et al. as inhibP. cauliflora extracts induced a cardiorenal protective response, preventing hemodynamic, functional, and remodeling changes. Paula et al. [Hydroalcoholic extracts of jabuticaba peels were also evaluated in the work by Rom\u00e3o et al. . The auta et al. investigAnthocyanin-rich fractions extracted from jambolan were evaluated in work by Chamnansilpa et al. . The resS. cumini fruit extracts employing HPLC.Anti-inflammatory and antinociceptive properties were demonstrated by Qamar et al. and QamaThe same flavonoid compound may be present in different parts of the plant, as is the case of myricetin, identified in the jambolan fruit in work by Soorya et al. and in iBaldissera et al. evaluateFruit production is one of the most prominent activities in the Brazilian market, especially when considering the development of new products resulting from the processing of these raw materials , as BrazFruit growing activity can generate a multiplier effect, with the possibility of moving the economy and promoting the development of stagnant places with few viable resources . Fruit pLinked to these conditions and aiming at the production of sensorially accepted foods with added nutritional value, scientific research promotes the development of juices, purees, jams, ice creams and/or other dairy desserts, and fermented, protein, or isotonic drinks, aiming at the addition of natural ingredients and, consequently, the incorporation of bioactive compounds, such as flavonoids ,110,111.Preparation of juices was proposed in the work of Rybka et al. when usiAnthocyanins were also present in cambu\u00ed juice, being quantified (311.7 mg) and expressed in mg of malvidin-3-glucoside per 100 mL of product . In jabuIce cream and dairy desserts are products much appreciated by the population, mainly due to their sensory and nutritional characteristics, since they appeal to a diverse audience and because of the presence in their formula of several nutrients, such as proteins, carbohydrates, lipids, calcium, phosphorus, and other minerals ,123.Considering this fact, B\u00f6ger et al. quantifiAccording to Neves et al. , alcoholFrozen fruit purees are products widely used in the preparation of other foods, due to their nutritional and functional characteristics, since they are rich in phenolic compounds, especially flavonoids . StafussTea, in general, is one of the most consumed beverages in the world, being a rich source of flavonoids, mainly due to the use of different parts of the plant in the product development, whether including leaves, stems, rhizomes or fruits . Sari etCambu\u00ed and jabuticaba processing by-products were used by Rybka et al. and RodrThis integrative review consists of a study based on the collection and analysis of scientific works related to the theme \u201cFlavonoids in plants of the Myrtaceae family\u201d, elaborated from the reading of online journals. The study presented the following steps: (1) formulation of the guiding question; (2) definition of search methods; (3) selection of scientific works; (4) analysis and evaluation of the studies included in the review; (5) presentation of the synthesis of the knowledge produced and published.A guiding question was proposed while conducting this study, namely \u201cWhat are the main flavonoids found in certain plants of the Myrtaceae family?\u201d. Data collection took place during the months of February and May 2022 in the following databases: Science Direct, Google Scholar, and Scielo. Basic descriptors used in the research process were as follows: Flavonoid AND Myrtaceae, in addition to specific terms for each plant species, as shown in P. cattleianum), Cambu\u00ed (M. floribunda), Gabiroba (C. xanthocarpa), Jabuticaba (P. cauliflora), and Jambolan (S. cumini).The following inclusion criteria were defined: studies published in the databases, in the period between 2016 to 2022, presented in full text, in English, Portuguese, or Spanish, and whose title and/or abstract referred to the topic of flavonoids in plants of the Myrtaceae family, such as Ara\u00e7\u00e1 .It was, therefore, possible to observe the importance of plants in the Myrtaceae family in terms of their phytochemical composition in relation to flavonoids, positive health effects, and the possibilities for their use in product development. A more significant number of scientific works associated with jambolan and jabuticaba were selected, with in vivo and in vitro experiments demonstrating these raw materials\u2019 bioactive potential. This way, an association was possible with specific health benefits, such as antioxidant, cardioprotective, antidiabetic, and anti-inflammatory activities.The preservation of flavonoids in jams, juices, wines, and other foods can also be observed, with anthocyanins being the predominant chemical class. Additionally, the integrative review employment as a methodology for this study proved relevant for achieving the objective. It guides the research practice and encompasses several scientific works on a subject."} +{"text": "Instead of \u201cDivision of Psychopharmacology, Department of Pharmacy, The Third People\u2019s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China\u201d, it should be \u201cDivision of Psychopharmacology, Department of Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China\u201d. In the published article, there was an error in affiliation 3. Instead of \u201cDepartment of Pathology, The Third People\u2019s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China\u201d, it should be \u201cDepartment of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China\u201d.In the original article, there was an error in affiliation The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "International Journal of Molecular Sciences, provides up-to-date information about the effects of a range of toxicants on the reproduction and development of many animal species, including humans. As so often is the case, the results from toxicant exposures to animal species can serve as sentinels for human toxicant exposures. Furthermore, reproductive systems, as well as developing embryos and fetuses, display greater risk from exposure to most toxicants, from pharmaceuticals to environmental contaminants. Developing new alternative models, including in vivo, in vitro, or in silico models, is critical to increasing our understanding of how toxicants affect reproduction and development. Not only is modeling critical, but it also is essential to be able to carry out research at all levels of scientific inquiry\u2014from molecules to integrated systems of organisms.Toxicology is an incredibly complex and diverse area of biomedical science that includes numerous areas of specialization. The overarching goals for investigators working in all areas of toxicology are to identify and define the exposures to potential toxicants, assess the risks, and mitigate the impacts. This Special Issue, Reproductive and Developmental Toxicology 2.0, in the Drosophila melanogaster [Caenorhabditis elegans [Currently, there are ten articles published in this Special Issue, providing a broad sampling of this vital and vibrant area of toxicology research. Several themes emerge when looking at the articles included in this Special Issue. First, there is a distinct emphasis on developmental toxicology, which indicates its importance in the broader area of toxicology. In the past, the assessment of developmental toxicity has utilized animal studies, primary mammals, the vast majority being rodents. However, new, more advanced, high-throughput modeling systems are rapidly being developed. As evidence of this shift in research focus, six of the ten articles report on studies that utilize non-mammalian testing systems, including nogaster ,2, sea unogaster , choroidnogaster , zebrafinogaster , Caenorh elegans . Regulat elegans , albeit elegans and embr elegans , resulti elegans ,4,5,9, a elegans , and PAH elegans . Environ elegans , which i elegans . Underst"} +{"text": "This Research Topic introduces selected articles on sport studies, mainly focused on methodological, interventional, and neuroscientific perspectives, that provide the basis for the title of the current volume. All of these topics are represented herein and we believe that our readers will value this balanced framework.With the aim of providing a panoramic view of the 27 articles that form this Research Topic, and properly assessing the contributions made, we present a transversal perspective from the following criteria:Trist\u00e1n et al.; Valenzuela et al.; Vergara-Torres et al.), the achievement goal theory , mental toughness , the self-efficacy theory , ecological momentary assessment , and mixed methods (Izquierdo and Anguera).1. Conceptual: Although most of the 27 articles are \u201coriginal research,\u201d with only one wholly fitting into the conceptual category, it is beyond any doubt that numerous articles contained herein highlight the conceptual implications of their research. This Research Topic includes some reference works focused on the self-determination theory, including the mini-theory of basic psychological needs , some have a psychometric special interest , some are observational , some are experimental/quasi-experimental , and others apply a combination of the preceding ones, using multimethod studies that employ, for instance, observational and selective methodology .2. Methodological: For this criterion, a variety of procedural orientations are differentiated in the empirical studies contained herein. Some of the studies use selective procedures . The majority of the instruments used consisted of questionnaires , scales , inventories , and even tests , although ad hoc instruments have been built for observational studies . Additionally, some studies used structural and functional magnetic resonance images .Among empirical studies, especially in those that use observational methodology, there is a clear interest in mixed methods, which have acquired so much relevance in recent years due to an eagerness to integrate qualitative and quantitative approaches. In some articles, the mixed method perspective is adopted, either in an explicit or implicit way , AMOS , AQUAD , GSEQ5 , GRETNA , HOISAN , LINCE PLUS , SPSS , and THEME . In particular, we highlight the new software \u201cFunction Estimation\u201d, contained in the MENPAS platform and described by Pastrana-Brincones et al..Moreover, the different types of software used in the studies featured in this Research Topic can be of interest to readers. Such software includes programs such as ALCESTE , cluster analysis , polar coordinates analysis , analysis of structural equations , factorial analysis , linear regression analysis , logistic regression analysis , sequential delay analysis , ANCOVA , ANOVA , T-Patterns detection , MANOVA , and temporal series . In the observational studies data, quality control was applied before the data analysis, using either consensual concordance , the kappa coefficient , or generalizability theory .A diverse range of data analyses are featured in this Research Topic, including content analysis and PSIXPORT apps.3. Technological: we would like to highlight a Brief Research Report describing the development of the B alert , athletes , basketball , quality of life , team coordination , elite sports , aerobic exercises , coaches and training , fatigue , fitness , soccer , sports injuries , taekwondo , and motor skills/task . Additionally, some reviews compile up-to-date knowledge on perceptual aspects of sports training , hypnosis (Li and Li), and the translation and validation of questionnaires .4. Scope of application: All the articles published in this Research Topic belong in the area of sport psychology, although many of them focus on specific subjects, such as physical activity (In short, with our best wishes, 27 articles that will help to expand the knowledge of our readers are presented in this Research Topic.Articles featured in this Research Topic offer a wide spectrum of theoretical and methodological contributions, and as editors, we would like to express our satisfaction with the materialization of these works and their transfer to the scientific community.The articles that make up this Research Topic already have a high number of \u201cviews\u201d according to inner metrics. All articles were published between 2021 and 2022. Of the 30 articles that were initially submitted, 27 were accepted, resulting in an acceptance percentage of 90%.AH-M coordinated the editorial work. MTA, JC, and VM-S contributed to the process. MTA wrote the article for this editorial letter. JC, AH-M, and VM-S reviewed the final version. All authors contributed to the article and approved the submitted version."} +{"text": "The increasing concerns over emerging infectious diseases and potential pandemics led to the formation of One Health, a collaborative, multidisciplinary approach to address the risks from human\u2013animal\u2013ecosystem interactions. This multi-sectoral approach is specifically important in Australia, a biodiverse country with unique flora, fauna, and many infectious diseases, including leptospirosis. Leptospirosis is a relatively rare but potentially fatal zoonosis, with an attributed mortality of around 60,000 deaths per year worldwide. In recent years, sporadic cases and alarming outbreaks of leptospirosis have been notified in many states and territories of Australia, noteworthily in 2018 and 2019. The sudden outbreaks in these two years have raised a question about the possibility of a more severe menace or a potential threat to both humans and animals. Amid the fight against leptospirosis, One Health has been shown to be an excellent and ideal framework, especially in Australia, the country that has taken the lead in zoonosis control using this approach. In this review, the focus will be put on the effectiveness and ethics of One Health in leptospirosis control under the Australian setting to further advocate the implementation of this framework for many other infectious diseases. Recent decades have witnessed increasing concerns over the risk of emerging infectious diseases and potential epidemics or pandemics . The majLeptospira species [Leptospirosis, a contagious disease caused by the pathogenic species , is a re species ,7, with species . While m species ,10, only species . The sym species .In recent years, sporadic cases and outbreaks of leptospirosis have been reported in many regions of Australia . The larIn this battle against leptospirosis, One Health is a potential approach , showingDistribution. Globally, there are roughly one million severe cases related to leptospirosis per year, while this figure for Australian settings is much lower, with about 2400 cases and more than 100 deaths annually [annually . Notifieannually are summannually . Within annually , which aannually .Pathology and risk factors. The leptospiral life cycle starts with shedding in the urine of the chronically infected animals, persisting in the ambient environment, acquiring a new host, and finally disseminating to the kidneys, turning them into reservoirs of pathogens [Leptospira species can enter the human body through skin cuts, abrasions, or mucous membranes in the mouth, nose, or eyes [athogens , and alsathogens . In term or eyes ,7, eithe or eyes ,19. The or eyes . People or eyes ,7,8, are or eyes ,7,8, avo or eyes .Diagnosis. The diagnostic process usually starts with the patient\u2019s symptoms and laboratory tests [Leptospira. In some cases, when physicians cannot identify the exact pathogen, understanding the epidemiology and pathology of potential infectious agents can help orientate the diagnosis. Referencing to leptospirosis, as a relatively rare bacterial disease in Australia [ry tests . In compry tests ,21. Howeustralia , a largeustralia ,7,8, makustralia . Based oustralia , which eTreatment. The treatment of acute leptospirosis in humans and animals depends mostly on antibiotics and supportive measures [measures ,22. Howemeasures . This ismeasures , as resimeasures is probameasures , to raismeasures , communimeasures , implyinmeasures , the appPrevention. In general, preventing contagious diseases requires knowledge about the sources, cycle, and pathology of infections. Unlike many other infections, leptospirosis is an endemic zoonosis [zoonosis , highly zoonosis ,7,8. Thezoonosis ,7,8. In zoonosis ,7,8, whiLeptospira species and has the potential to eradicate the pathogen from the human and animal community. However, practical and cost challenges can deter this strategy, especially in the Northern Territory of Australia [More importantly, this One Health approach might have broadened the scope of preventive measures, from defence to control and eradication . Knowleustralia . To advoFurthermore, the ambient environment where the leptospiral strains temporarily exist should also be investigated. As rodents are potential reservoirs, measures targeting these mammals\u2019 habitats, including the removal of rubbish and food sources, are advocated ,8, partiHarm principle. This principle can relate to those deliberately trying to harm, or neglecting their responsibilities, which might inflict harm on other people [r people . In the r people , which cr people . While tr people . Howeverr people , given tr people . Howeverr people ,3, all tr people . After cr people , the OneDuty of care. The original concept of this aspect was to clarify the responsibilities of healthcare workers in the event of fatal outbreaks [Leptospira species. Measures to maintain the safety of the environment must also be carried out to mitigate the presence of the pathogen in the natural habitat, i.e., keeping livestock away from the water source in suspected areas. In regions that usually suffer from floods and leptospirosis, assistance from One Health experts to minimise the damage and consequent risks could prevent disaster after disaster. Provided that the duty of care principle aims at avoiding predictable actions that might cause harm to other people, One Health is an ideal approach, allowing us to foresee all the potential risks and the accompanying solutions.utbreaks , as thisutbreaks . Thus, tSolidarity. At the most basic level, solidarity \u201ccomprises manifestations of the willingness to carry costs to assist others with whom a person recognises sameness or similarity in at least one relevant respect\u201d [respect\u201d . This corespect\u201d . In the respect\u201d , implyinrespect\u201d for diffrespect\u201d , whereasrespect\u201d ,34, the respect\u201d . This imHealthcare equity. In close association with solidarity, One Health has a significant potential to promote healthcare equity, specifically in low- and middle-income countries [ountries . Followiountries , governmountries . Additioountries , could bResearch ethics. One Health plays an essential role in ensuring research ethics, as it is the key to maintaining all of the above ethical aspects of this approach. The foundation of One Health is based in multiple fields, from health to the social and environmental sciences [sciences ,2, implisciences , for thesciences . As longsciences , it appesciences . By follIn conclusion, as prioritisation and resource allocation always require comprehensive considerations, including ethical principles, effectiveness, socioeconomic status, etc., a multi-sectoral approach such as that advocated by One Health is critically useful and necessary to address all of the related issues in leptospirosis control. The feasibility of One Health is mainly reflected in the context of economic, social, and political forces. Whereas One Health\u2019s effectiveness is best expressed in the process of diagnosis\u2013treatment\u2013prevention, it is better to consider its necessity by analysing the underlying ethical principles. Together, both aspects can form a bigger picture about the role of the One Health approach in controlling leptospirosis as well as other infectious diseases and how to properly implement it in real settings."} +{"text": "Somatization and number of diseases are interrelated variables, whose association with stress-coping strategies, according to sex, has not been investigated. Therefore, the aim of this study was to investigate such association in a sample of the Mexican general population. The general population was invited to answer an electronic questionnaire via the social networks\u2014e-mail, WhatsApp and Facebook\u2014by the research team. A sample of 1008 adults was obtained, of which 62.2% were women, in whom we detected higher levels of negative psychological variables, somatization and number of diseases and lower levels of sleep quality. Positive moderate correlations were found between depresion, anxiety and stress with somatization, on one hand, and with the number of diseases, on the other, and negative moderate correlations were found between sleep quality and the two dependent variables. As for the coping strategies, self-blame, behavioral disengagement, denial, self-distraction and substance use were positively correlated with somatization. Of these, self-blame, substance use, and self-distraction also showed a positive correlation with number of diseases in both sexes. Negative correlations were detected for active coping and the two dependent variables in men and for religion and planning with somatization in women. In conclusion, the coping strategies showed significant correlations with somatization and number of diseases in both sexes. Somatization, described as the \u201ctendency to experience and communicate somatic stress and to seek medical help for it\u201d , has beeThe number of diseases is also increased in women when compared with men ,6, whichIn a previous report, we showed that anxiety, depression and sleep quality were factors related to somatization in both sexes. Therefore, the aim of this study was to determine the association between coping strategies and both somatization and number of diseases, considering the previously associated variables of anxiety, depression and sleep quality. The study was performed in order to detect the coping strategies that are positively or negatively correlated with these two factors in each sex, which would permit the design of future preventing programs.An electronic questionnaire with sociodemographic and psychological instruments was sent via social networks, including WhatsApp, Facebook and e-mail, to the general population by the research team; this population included university students, relatives, friends, colleagues and acquaintances, many of whom re-sent the questionnaire.The study was approved by the ethics and research committee of the Health Sciences University Center of the University of Guadalajara, and the participants gave their consent to participate in the questionnaire.The socio-demographic data included sex, age, whether the participants had a romantic partner, schooling, whether they had children, whether they had a job, socioeconomic level , monthly extra money (excluding necessary expenses), daily free hours and weekly physical activity hours, the presence of 21 different diseases , thyroid diseases, migraine, skin diseases , sinusitis, kidney/bladder problems, anorexia/bulimia, hearth attack/angina pectoris, cerebral stroke, high cholesterol levels, anxiety and depression problems that require medication) and any additional disease in the last 6 months.Sleep quality was measured with item 2 (which consists of 5 items) of the OVIEDO sleep questionnaire; these 5 questions were related to sleep problems and had 5 frequency options, from never to 6\u20137 days in a week . FinallyThe psychological measures included were: somatization, measured with the Patient Health Questionnaire 15 (PHQ-15), which evaluates 15 somatic symptoms with 3 frequency options for each symptom, i.e., not at all, bothered a little, bothered a lot ; stress,p value < 0.05 was considered significant.To describe the qualitative variables, we used frequencies and percentages, and for the quantitative ones, we used means and standard deviation. In order to compare the number of diseases and somatization between sexes, the Man\u2013Whitney U test was used, considering the non-parametric distribution of the variables. Alpha Cronbach test was used to determine the reliability of each scale and sub-scale utilized. To perform comparisons between the psychological variables and sleep quality with the two dependent variables, we used the Spearman correlation test, considering the non-parametric distribution of the variables. In order to detect the distribution of the data, the Kolmogorov\u2013Smirnov test was used. Finally, a multiple regression analysis, with the stepwise method, for both dependent variables by each sex was performed, in order to determine the variables most associated with somatization and number of diseases in men and women. All analyses were carried out with the software SPSS v. 25, and a p < 0.05).We estimate that the questionnaire was sent to about 5000 persons through the different social networks, achieving a response rate of 20%. After excluding the questionnaires submitted by underage persons (24 persons), a total of 1008 participants were included, of which 62.2% were women. The socio-demographic data of the participants are reported in The most frequent reported diseases in both sexes were anxiety, depression, skin problems, overweight, migraine and colitis/irritable colon, while the least frequent were cancer, cerebral stroke and heart attack .The Cronbach alpha test for all the instruments used was above 0.7. In the case of the sub-scales of the brief COPE, most of them had scores above 0.6, with the exception of self-distraction, behavioral disengagement, denial and acceptance, which had scores above 0.5. In the case of the sub-scale venting, the Cronbach alpha was low, i.e., 0.35; therefore, we did not use this sub-scale in order to perform correlations and comparisons. When we compared the somatization and number of diseases between sexes, women reported significantly higher somatization, number of diseases, stress, depression and anxiety than men; likewise, women reported lower sleep quality than men .In the bivariate correlations, both sexes showed significant positive moderate correlations between stress, anxiety and depression with somatization, on one hand, and with the number of diseases, on the other, with higher correlations for depression in women and for anxiety in men. In addition, sleep quality showed significant negative moderate correlations with both dependent variables .p <0.01; for women, r = 0.313, p < 0.01. The same correlation with depression was, for men, r = 0.311, p < 0.01; for women, r = 0.306, p < 0.01. The correlation with stress was, for men, r = 0.290, p < 0.01; for women, r = 0.237, p < 0.01. The correlation with sleep quality was, for men, r = \u22120.262, p < 0.01; for women, r = \u22120.328, p < 0.01. When overweight was also excluded from the number of diseases, the correlations remained similar as those found when excluding anxiety and depression problems. Somatization and number of diseases showed significant positive moderate correlations between them in both sexes: men: r = 0.545, p < 0.001, and women: r = 0.547, p < 0.001.When anxiety and depression problems were not included in the number of diseases, the correlations between the three psychological variables diminished, but were still significant for both sexes. The correlation of number of diseases with anxiety was as follow: for men, r = 0.380, In relation to coping strategies, women showed significant low positive correlations between somatization and self-blame, denial, behavioral disengagement, substance use, self-distraction and humor, and significant low negative correlations between somatization and planning and religion. For the number of diseases, women showed significant low positive correlations with self-blame, substance use, denial, behavioral disengagement, self-distraction, humor and instrumental support.Men showed significant low positive correlations between somatization and self-blame, behavioral disengagement, denial, self-distraction and substance use. For the number of diseases, men showed significant low positive correlations with self-blame, substance use and self-distraction, and significant low negative correlations with humor and active coping.p < 0.01), weekly physical activity hours , monthly extra money , whether they had children , schooling , socioeconomic level , daily free hours and whether they worked , and a low positive correlation with smoking frequency . Sociodemographic variables also showed low but significant negative correlations with somatization and number of diseases. In women, we found negative correlations between somatization and age , weekly physical activity hours and whether they had children .In men, we found negative correlations between somatization and monthly extra money , socioeconomic level and weekly physical activity hours , and a low positive correlation with smoking frequency (r =0.110 p < 0.05). In men, we found low but significant negative correlations between the number of diseases and weekly physical activity hours , and a low positive correlation with age and smoking frequency .For the number of diseases, in women, we found low but significant negative correlations with whether they had children and anxiety. In contrast, for number of diseases, the most associated variables were sleep quality (negatively associated), anxiety and schooling .We found that somatization and number of diseases were associated and that they were also associated with the main negative psychological variables, i.e., anxiety, depression and stress. Likewise, they were negatively correlated with sleep quality, in both sexes. We also showed that typical maladaptive coping patterns were positively correlated with somatization and number of diseases (mainly self-blame) in both sexes and that active coping correlated negatively with somatization and number of diseases only in men. As previously shown, negative psychological variables, somatization and number of diseases reached higher levels in women than in men ,3,4,5. WThese differences can be explained by considering that the population studied was mainly young and could present more psychological problems and less metabolic ones. With respect to the correlation analysis, we found that the variables most associated with somatization in both sexes were anxiety, depression and stress, with moderate positive correlations, as well as sleep quality, with moderate negative correlations. The coping strategies showed lower correlations with somatization in both sexes. It is of interest that self-blame showed the highest correlations in both sexes, followed by behavioral disengagement, denial, self-distraction and substance use; these correlations indicate a possible indirect correlation between these coping strategies and somatization, considering that these strategies were positively correlated with the negative psychological variables in both sexes (data not shown) and are typically considered as maladaptive coping strategies ,22. AddiThe coping strategies negatively correlated with somatization were active coping in men, and religion and planning in women, which coincides with the fact that these strategies have been classified as adaptive ,22. HoweAs previously shown, a positive moderate correlation was found between somatization and number of diseases in both sexes . This suIn addition, self-blame and substance use were the only coping strategies positively associated (low correlation) with number of diseases in both sexes; women also showed low positive correlations with behavioral disengagement, denial and humor, while men showed low negative correlations with humor and active coping. These results confirm the correlations found for somatization, although for this variable, a decreased number of associated coping strategies and a diminishment in the strength of the associations were observed. These changes were expected, considering that disease presence is a variable related to more causes than somatization, which, in turn, is more associated with psychological variables.The multivariate analysis confirmed the results of the bivariate analysis, indicating that depression, number of diseases, sleep quality and anxiety were the variables that most explained the variability of somatization. Likewise, sleep quality and anxiety were the variables that most explained the number of diseases. These findings coincide with our previous report where slThis study has the following limitations: the sample was predominantly young and was not randomly selected, which could decrease the representativeness of the Mexican population, restricting it to young and educated people, from a medium socioeconomic level, who have access to the internet and social networks, and not representing older people and those from lower socioeconomic levels. In addition, the cross-sectional design of the study did not permit us to demonstrate causality between the studied variables, being bilateral relationships plausible, mainly between sleep quality and somatization and number of diseases. Finally, the estimated response rate of the questionnaire was low (20%), which can represent a bias by considering that it could be answered by people who had more interest in the theme and/or who presented more emotional problems/concerns. In conclusion, somatization and number of diseases showed a higher frequency in women than in men. These variables were mainly related (positively) with the negative psychological variables of depression, anxiety and stress, as well as with sleep quality (negatively) in both sexes. Likewise, these variables showed lower but significant positive correlations with some maladaptive strategies, mainly, self-blame, in both sexes. Additionally, some of these strategies, considered as adaptive, showed negative correlations with somatization and number of diseases, being more constant in the case of men, where active coping was negatively correlated with these two variables. Humor showed different correlations in men and women, suggesting that this strategy is adaptive in men but maladaptive in women. Further studies with larger sample sizes, longitudinal designs and performed in different populations should be performed to confirm these results."} +{"text": "The objective is to identify the risk factors for necrotizing enterocolitis (NEC) in neonates by a meta-analysis, and to provide a reference for the prevention of NEC.The databases, including Chinese Biomedical Literature Datebase, China National Knowledge Infrastructure, Wanfang database, and Weipu Periodical database, PubMed, Web of Science, Embase, Cochrane Library, were searched for studies on the risk factors for NEC in neonates. The meta-analysis was carried out with the aid of Stata software.A total of 52 studies were included, with 48 case-control studies and 4 cohort studies. There were 166,580 neonates in total, with 33,522 neonates in the case group and 133,058 neonates in the control group. The meta-analysis showed that gestational diabetes , premature rupture of membranes , low birth weight , small for gestational age , septicemia , blood transfusion , congenital heart disease , respiratory distress syndrome , premature birth , pneumonia were risk factors for NEC in neonates. Breastfeeding , take probiotics , prenatal use of glucocorticoids , Hyperbilirubinemia were protective factors for NEC in neonates.Gestational diabetes, premature rupture of membranes, low birth weight, small for gestational age, septicemia, blood transfusion, congenital heart disease, respiratory distress syndrome, premature birth, and pneumonia may increase the risk of NEC in neonates. Breastfeeding, taking probiotics, prenatal use of glucocorticoids, and Hyperbilirubinemia may reduce the risk of NEC in neonates. Necrotizing enterocolitis (NEC) in neonates is a severe muti-factorial disease characterized by intestinal necrosis in the ileum, jejunum, and colon. It is one of the leading causes of morbidity and mortality in preterm infants , with whChina National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, Embase and Cochrane Library were searched to systematically collect published studies on risk factors of NEC in neonates. The search strategy of combining keywords and subject terms was adopted. The Chinese search terms were \u201cnewborn\u201d, \u201cnecrotizing enterocolitis\u201d, \u201crisk factors\u201d, \u201ccase-control study\u201d, \u201ccohort study\u201d, etc. English search words \u201cEnterocolitis, Necrotizing\u201d, \u201cInfant, Newborn\u201d, \u201crelative risk\u201d, \u201ccohort\u201d, etc., supplemented by manual search and literature tracing.Inclusion criteria: 1. The diagnosis of NEC is clear; 2. The study type was a case-control study or cohort study; 3. The subjects were neonates (<28 days); 4. The original data is available. The OR (odds ratio) value and 95% confidence interval (CI) are provided, or the OR value and 95% CI can be calculated from the data.Exclusion criteria: 1. Conference summary, comments and review articles; 2. Unable to extract effective outcome indicators from the literature; 3. The experimental design is not rigorous ; 4. Unable to get a full text; 5. The sample size is too small.Two researchers strictly followed the inclusion and exclusion criteria to independently conduct literature screening, quality evaluation, data extraction, and discuss possible differences to reach an agreement. The final results were confirmed by more senior researchers. The Newcastle-Ottawa Scale (NOS) was used2 statistic were used to evaluate the heterogeneity, and the test level was set as 0.1. If the heterogeneity test results were P\u2009>\u20090.1 and I2\u2009<\u200950%, the pooled effect size OR and 95% CI were calculated using the fixed effects model. Otherwise, the random effect model is used to calculate; Sensitivity analysis uses different models to analyze the same data. Egger's or Begg's test was used to evaluate publication bias, and Stata12.0 was used for statistical analysis.The Q test and IA total of 5,728 relevant articles were obtained through preliminary screening, and 3,931 articles remained after being re-selected by Endnote software. Ulteriorly, 3,475 articles were excluded after reading the title and abstract, and 117 articles remained for further evaluation. Finally, after reading the full text, 52 articles were included according to the inclusion and exclusion criteria, as shown in According to the risk factors involved in the included literature, gestational diabetes, premature rupture of membranes, cesarean section, low birth weight, small for gestational age, sepsis, blood transfusion, congenital heart disease, respiratory distress syndrome, mechanical ventilation, breast feeding, probiotics, preterm delivery, pneumonia, prenatal use of glucocorticoids, hyperbilirubinemia, ect., were selected for analysis. Heterogeneity test results showed that there was heterogeneity among the studies of diabetes in pregnancy, premature rupture of membranes, cesarean section, small for gestational age, sepsis, blood transfusion, congenital heart disease, respiratory distress syndrome, mechanical ventilation, breast-feeding, probiotics, preterm delivery, pneumonia and hyperbilirubinemia, and the random effect model was used to combine the effect amount. In contrast, there is no heterogeneity in other related factors, and the fixed effect model is used to combine the effects. The meta-analysis results demonstrates that: Cesarean section and mechanical ventilation were not statistically significant with NEC in neonates. Gestational diabetes mellitus, premature rupture of membranes, low birth weight, small for gestational age, sepsis, blood transfusion, congenital heart disease, respiratory distress syndrome, premature birth and pneumonia were risk factors for NEC in neonates. Breastfeeding, probiotics, prenatal glucocorticoid use, and hyperbilirubinemia were protective factors for NEC in neonates, as shown in P\u2009<\u20090.05), as shown in For the screened risk factors, the fixed effect and random effect models were used to recalculate the combined effect size. The calculation results of these two models were basically consistent, indicating that the results of this study were basically reliable. However, the results of premature rupture of membranes are not robust enough and should be treated with caution. The results of Egger's or Begg's test suggest that the results of sepsis, probiotics, and pneumonia are biased Due to the immature intestinal function and slow intestinal peristalsis of low birth weight infants, food residues are easy to be detained and fermented, providing a good environment for bacterial growth, leading to a large number of bacterial proliferation; (2) The intestinal microbiota of low birth weight infants is very immature, and direct contact with pathogenic microorganisms will cause inflammation related to mucosal damage, leading to NEC .This meta-analysis showed that small for gestational age (SGA) was a risk factor for NEC. SGA infants have a high probability of NEC, neonatal asphyxia, brain injury and respiratory distress syndrome . One stuThis meta-analysis showed that septicemia, congenital heart disease, respiratory distress syndrome, and pneumonia were risk factors for NEC. In severe infection, the body is in a state of inflammation activation, producing a variety of inflammatory transmitters. These substances directly or indirectly cause damage to the intestinal mucosa, and then participate in the occurrence and development of NEC , 63. MeaThis meta-analysis showed that blood transfusion was a risk factor for NEC. The possible pathogenesis of NEC is as follows: the inflammatory mediators such as TNF-\u03b1, IL-6, and PAF produced during the processing of whole blood and the storage of red blood cells, and the residual white blood cells, free hemoglobin, red cell membrane fragments, etc. promote the occurrence of NEC. The pathological changes of red blood cells occurred during storage, including decreased erythrocyte deformability, increased oxygen affinity ability and decreased nitric oxide resulting in the loss of vasodilator activity, etc., resulting in the failure to improve intestinal microcirculation perfusion flow after blood transfusion; NEC may be caused by anemia .This meta-analysis showed that preterm birth was a risk factor for NEC. Due to the unsound development of the enteric nervous system and poor regularity of small intestinal peristalsis, premature infants are prone to excessive bacterial growth and gas after food fermentation, and are prone to NEC .This meta-analysis showed that breastfeeding, probiotics, prenatal glucocorticoid use, and hyperbilirubinemia were protective factors for NEC. Breast milk is known as the most natural and safe natural food for infants and young children, containing nutrients and antibodies necessary for the development of organized organs, especially beneficial antibodies, which can help maintain the immune function of newborns, inhibit the inflammatory reaction, and speed up the repair of the damaged intestinal mucosa . CompareThis study has some limitations: First, sensitivity analysis found that the results of premature rupture of membranes were not robust enough. Therefore, the relationship between premature rupture of membranes and NEC in neonates needs further study. Secondly, there exist differences in sample size, case selection, and definition of exposure factors among the studies, which may lead to heterogeneity among the studies and have a certain impact on the results. Finally, only Chinese and English literature ware included in the included study, and literature published in other languages could not be analyzed, which may result in language bias.We conducted a meta-analysis to evaluate the risk factors of NEC. This meta-analysis showed that gestational diabetes mellitus, premature rupture of membranes, low birth weight, small for gestational age, sepsis, blood transfusion, congenital heart disease, respiratory distress syndrome, premature birth, and pneumonia maght increase the risk of NEC in neonates. Therefore, perinatal health care should be strengthened to reduce the incidence of neonatal complications, so as to prevent the occurrence of NEC in neonates."} +{"text": "For decades, the concept of \u201cdisease-modifying\u201d treatment has been used profusely in several neurodegenerative diseases including Parkinson's disease (PD). This concept has been employed sometimes as an accomplished goal, and many more as a wishful thinking objective. In addition, the related concept of neuroprotective therapy has been widely used and a quick search on Medline shows a steady increase in the number of papers on this issue over time.As Morant et al. pointed Perhaps it is time to ponder over these two related concepts: disease modifying and neuroprotective therapies, at least in relation to PD. First, it is important to have (more or less) clear definitions, and then, we can discuss whether we have or we may have (or not) disease modifying and neuroprotective therapy for PD.To begin with, the definition of \u201cdisease-modifying\u201d treatment varies both within and between neurodegenerative disorders, and terminology in current regulatory guidelines also lacks consistency . CummingHere it must be pointed out that, in theory, any disease-modifying treatment may have symptomatic effect as well, possibly masking the modifications produced in the disease. Recently, Vijiaratnam et al. reviewedTo date, no disease-modifying drugs has been found, although some promising candidates are still in the pipeline including exenatide and gene therapy .And still, probably, a real disease-modifying treatment for PD already exists and has been used for decades: Physical exercise. As Eric Ahlskog already suggested a decade ago, \u201coften overlooked (\u2026) is the potential benefit of sustained vigorous exercise on PD progression\u201d .In this short review, we collect and summarize, the most relevant data of physical exercise as a symptomatic and preventive measure, and its potential for disease modifying therapy for patients with PD.de novo PD patients. They found statistical differences in Unified Parkinson's Disease Rating Scale (UPSRS) motor score in the high-intensity group compared with the usual care group. Another interesting study was carried out by van der Kolk et al. \u201334, suffIf physical exercise is symptomatically effective, probably prevents neurodegenerative diseases, and has potential neuroprotective mechanisms, why is it not universally used?This conundrum may be explained by several factors. There are barriers to exercise , 38, as In summary, although physical exercise is inexpensive, its use as a treatment requires a complete change of strategy. Exercise training would be considered the first antiparkinsonian measure, even before (or at least at the same time) than drug therapy is added , 38, 39.Finally, physical exercise would be a practical and inexpensive approach for those patients at risk for PD (such as LRKK2 carriers).PG conception and design, interpretation of data, drafting the submitted material, and critical review. RL and JM drafting the submitted material and critical review. All authors contributed to the article and approved the submitted version.PG received research support from Allergan and UCB, personal compensation as a consultant/scientific advisory board from Italfarmaco, Britannia, Bial, and Zambon and speaking honoraria from Italfarmaco, Zambon, Allergan, and Abbvie. JM has received honoraria as a speaker from AbbVie, Allergan, Bial, Krka, Merz, Ipsen, Italfarmaco, Medtronic, TEVA, and Zambon; travel grants from AbbVie, Allergan, Bial, Italfarmaco, TEVA, Merz, Krka and Zamb\u00f3n; research grants from AbbVie, Allergan, Merz, Italfarmaco, and Zambon; and participated in advisory boards of AbbVie, Allergan, Bial, Merz, Italfarmaco, Lundbeck, Orion, UCB, and Zambon. RL has received honoraria for lecturing and advisory board from AbbVie, Lundbeck, UCB, and Italfarmaco and research grants from the European Commission and Instituto de Salud Carlos III.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Instead of \u2018Department of Anaesthesiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa\u2019 it should be \u2018Surgeons for Little Lives, Department of Paediatric Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa\u2019.In the published article, Elghobashy A, Scribante J, Perrie H, Nel D. Anaesthetists\u2019 knowledge of airborne infections S Afr J Infect Dis. 2022;37(1):a351. The publisher apologises for this error. The correction does not change the study\u2019s findings of significance or overall interpretation of the study\u2019s results or the scientific conclusions of the article in any way."} +{"text": "Standards of care offer doctors and patients the confidence that an established quality, evidence-based, care is provided, and represent a tool for optimal responding to the population\u2019s needs. It is expected that they will increasingly express a multimodal relationship with gynecologic laparoscopy. Laparoscopy is, now, a standard procedure in operative gynecology, standards are embedded in many laparoscopic procedures, standardization of the skills/competency assessment has been progressively developed, and the proof of competency in laparoscopy may become a standard of care. A continuous development of surgical education includes standard equipment , standardized training, testing (and performance) assessment, educational process and outcome monitoring/evaluation, patients\u2019 care, and protection, etc. Standards of care and training have a reciprocally sustaining relationship, as training is an essential component of standards of care while care is provided at higher standards after a structured training and as credentialing/certification reunites the two. It is envisaged that through development and implementation, the European wide standards of care in laparoscopic surgery would lead to effective delivery of better clinical services and provide excellent training and education. Standards of Care offer doctors and patients the confidence that an established quality of the service is provided. The Royal College of Obstetricians and Gynaecologists have described service standards as \u201cstandards of clinical care which the college would expect units and hospitals to adopt in relation to the quality of patient services, training opportunities and participation in national data gathering of relevance to clinical accountability and effectiveness\u201d [iveness\u201d .Evidence-based care is a solid and helpful concept, with influences not limited to the specialists\u2019 activities, but also to the nurses\u2019 ones, and is still debated at present .Laparoscopy has shown in the last decades a steep evolution, including indications, procedures, increased patient comfort, advanced appropriate surgical skills, tools, and, beyond all this, a difference in the medical care paradigm. The changed dimension of the incision, or in the number of incisions (toward a single one) or, even, to the natural orifice surgery , depict Standards are the criteria we can use to analyze quality. It is the institution\u2019s responsibility to develop and to monitor standards, as a prerequisite in the process of pursuing higher quality. A diversity of standards responds to different needs, views, and organizations. Accreditation, ethics, client rights, billing, and professional/criminal records are only some examples.Standards in laparoscopy may include criteria related to the equipment, facilities, surgical procedures, surgeons\u2019 credentials/expertise, etc.Standards of Care not only ensure that patients receive the best available care, but they are also a tool for better responding to the population\u2019s needs. It is not possible, these days, to conceive such a system without including quality standards.The application of standards should aim to obtain the expected outcome and to minimize risks for the population. Working with patients in the process of developing and implementing them would be a good option to obtain their partnership. Seeking beneficiary feedback and linkage to other existing programs represent another strategy in ensuring acceptance, support, and social integration.As a procedure\u2014but also as a philosophy\u2014laparoscopy is the gold standard of care worldwide in the treatment of many abdominal pathologies such as appendicitis, cholecystitis ,5,6, or Standards of care and gynecologic laparoscopy have a multimodal relationship.First, laparoscopy is, now, a standard procedure in operative gynecology [1. necology . It becanecology , endometnecology ), ovarianecology , or tubanecology . More renecology , hysterenecology or myomenecology .Laparoscopic urogynecology, in particular, showed relevant evolution and adaptation, especially after the FDA warning, allowing meshes to be used only for pelvic organ prolapse (POP) . LaparosGynecologic oncology is another field where laparoscopy became the reference, and recommended, procedure. Endometrial cancer and pelvic lymphadenectomy represent such cases; cervical and ovarian cancer, and robotic-assisted surgery are areas with continuous assessment and development ,22. CervRecent developments were reported. Laparoscopic minilaparoscopy, with shortened hospital stay and better esthetical outcomes [outcomes ,32, provoutcomes or hysteoutcomes ,35,36 whoutcomes . Single-outcomes and was outcomes , hystereoutcomes ,41,42\u2014inoutcomes ,44\u2014or cooutcomes . Furtheroutcomes . Vaginaloutcomes , and prooutcomes , hystereoutcomes ,48,49,50outcomes . Laparosoutcomes , were proutcomes ,54,55,56Another recent, unfortunate development, which profoundly influenced the laparoscopic surgery, was (and still is) the COVID-19 pandemic. Presently, \u201cthere is no consensus on limiting or restricting laparoscopic or robotic surgery\u201d \u2014an asserSecond, standards are embedded in, now, a great number of laparoscopic procedures. In general surgery, a good recent example is represented by the laparoscopic right hemicolectomy [2. olectomy . In gyneolectomy . These polectomy , or haveolectomy or robotolectomy hysterecolectomy . Standarolectomy and was olectomy ,69 or ceolectomy cancer. olectomy .In urogynecology a search for better, easier, procedures, with better postoperative outcome, drove physicians to standardize modification of well-established procedures\u2014such as the Burch colposuspension \u2014or to fiThe COVID-19 pandemic imposed specific recommendations/standards related to the perioperative management for gynecologic laparoscopy, such as preoperative screening and testing, with subsequent preprocedure quarantine, online follow-up, and psychological support ,59,60. EStandardization is also visible in the sterilization or disinfection equipment, facilities, and related procedures (and training) . This isStandards of the laparoscopic procedures\u2019 documentation are essential for both assessment of care quality and for research .Third, standardization of the skills/competency assessment has been progressively developed. A structured assessment of laparoscopic assistant skills (SALAS) was developed to assess camera navigation and was validated for laparoscopic cholecystectomies [https://www.flsprogram.org, accessed on 13 February 2022). Developments on FLS were evaluated as a proficiency-standard in advanced laparoscopic surgery [3. ectomies . The samectomies . The objectomies . The Gloectomies \u2014measuresectomies . Fundameectomies is considered, by some, as the standard for skills assessment . An ObjeFinally, the proof of competency in laparoscopy may become a standard of care [4. of care . Without of care . The Int of care . Standar of care and for of care \u2014but, app of care . These s of care . Under t of care is manag of care .In Europe, such accreditation standards were implemented by the European Society for Human Reproduction and Embryology (ESHRE) in 1997, and are comprised of four levels of expertise . A jointESGE, in collaboration with the European Academy of Gynecological Surgery (EAGS), has also developed training models, structured training programs and a ceA French version of GOALS proved to measure trainers\u2019 progress . The SocAs it could be easily deducted, skill standards and surgical competency express the outcome of training.Training involves standards as an essential constituent. Educational requirements vary according to the level of training and to the category of personnel. These standards may be more flexible or rigorous, depending on the needs of the trainees, and the level of the curriculum. Education and assessment instruments should be adapted to training/practice in as many institutions as possible, to obtain standardization and broad application [lication . GeneralTraining in gynecologic laparoscopy follows the same, general, pattern, and expresses, at the same time, noticeable particularities.Different surveys reported an increased interest in a standardized curriculum in gynecologic laparoscopy ,121, incStandardized training and education in this field was developed in many regions/countries of the world [he world ,125,126.he world . Specifihe world ,129, virhe world , advancehe world ,134,135,he world ,119,136.he world ,138, moshe world , a standhe world ,139 or phe world , as wellhe world ,140,141.he world , visio-she world , or sutuhe world ,142. Thehe world . Some auhe world ,143.One of the most comprehensive standardizations of endoscopic surgical training is offered by ESGE , as presented previously. Its face and construct validity were reported . GESEA iTraining was significantly influenced by recent available evidence, by medical policies, or by the context. After the LACC trial , fewer LStandard equipment may bring value for research and development. An eloquent illustration is the box trainer. Reports on its use, as a standard component of the study, addressed various aspects, as the training on an open box [open box , elaboraopen box , new camopen box , value oopen box , translaopen box , as wellopen box ,155, VR open box ,157, or open box .Standardized testing and assessment, validated rating scales, and procedure-specific checklists, are of utmost importance in developing and conducting training programs [programs ,158,159.programs . The preprograms and traiprograms ,161. Simprograms ,162,163,programs , or as aprograms . Scoringprograms . Computeprograms .Performance standards can be set by different approaches: laparoscopic experts considered as reference, contrasting groups method or Angoff method [f method ,168. Thef method .The educational outcome represents, evidently, the result of the above-mentioned education. As a meta-analysis, though, its standardization was embedded in the previously mentioned structured training, equipment, testing, performances benchmarks, and credentialing. Acquisition of a required knowledge level [ge level , and stage level ,167, havge level ,125. Thige level , VR [130ge level ,119 surgge level and, eveThe educational process assessment is essential, in validation with the curriculum [rriculum ,126 or erriculum . Relatedrriculum , while arriculum . Resultsrriculum . Anotherrriculum . Relativrriculum , while arriculum .It seems that there is a need for more research in this field .Patients\u2019 care and protection represents not only a training standard, but also, now, an ethical criterion. It was supported, in recent years, by the introduction/validation of simulation-based training, and, even more, by normalizing it as a necessary stage in a structured education, before OR surgical training [training ,169. Laptraining .Monitoring is the process through which one verifies if standards are met [ are met . Standar are met .Organizations use various methods for monitoring: process supervision, supervisory visits, provider surveys, trainees\u2019 assessments and feedback, educational planning, case management, program reviews, etc. . The EurStandards of care and training have a reciprocally sustaining relationship.(a) Training is an essential component of standards of care, to support highly complex training programs.One of the fundamental concerns of EBCOG relates to issues around inequity concerning health service provision across Europe and its impact on the quality of training for our future generation of \u201cdoctors in training\u201d to sustain high quality services in Europe. This is especially important as \u201cEuropean integration allows free movement of persons, services, capital and goods\u201d . TherefoA supplementary benefit for the patients is that the training program and resources are founded on evidence-based practice and on solid ethical principles.(b) Care is provided at higher standards after a structured training.As stated previously in this text, the most important outcome of training is safe and good surgical performance. Another important goal is the avoidance of\u2014or finding solutions for\u2014difficult situations . The conStandardized surgical skills assessment could be useful for residents and not necessarily for gynecologic surgeons in practice . DiffereSimulation-based training gained a lot of interest, in recent decades, even if box training tasks do not have the variability, complexity and environment of the real OR (advanced) surgery [ surgery . We depiBesides increasing (basic and advanced) psychomotor laparoscopic skills in a dry lab , laparosThose results were obtained when related to different simulation training tools. Box training was already mentioned. VR-based training was reported to help transfer/increase skills in gynecologic laparoscopic surgery in trainees/gynecologists with minimal surgical experience ,190,191.As a supplementary benefit, a structured training could enhance the quality of the OR performance by standardizing the respective procedure\u2014as it was reported for the total laparoscopic hysterectomy .No matter the simulation tool, many authors support the idea that, compared to conventional clinical training, simulation-based training is superior, in terms of OR surgical proficiency, for both basic ,194,195 However, surgical competence could depreciate over time when based exclusively on simulation training . AnotherThe best of the worlds resides in combining standardized, structured theoretical, simulation-based and live-surgery/OR training, as suggested by a recent systematic review .(c) Credentialing/certification, mentioned previously, reunites the two directions of the standards of care\u2013training relationship. One of the results is that certification and licensing are closely related to training requirements [irements . Specialirements . Such a irements . The misirements \u2014or theirirements . There iirements . A very irements . There airements .In the end, the most important accomplishment of training is both for patients and for providers: the certifying and continuously ensuring the fitness to practice.It is envisaged that by implementation, the European wide standards of care, in close harmonization with the personalized medicine, would ultimately lead to effective delivery of not only clinical services but indeed provide excellent (standardized) training in these units."} +{"text": "Nanomaterials, which aims to publish original and review papers on new scientific and applied research and make boundless contributions to the finding and understanding of the reinforcing effects of various nanomaterials on the performance of polymer nanocomposites. This Special Issue also covers the fundamentals, characterization, and applications of fiber-reinforced polymer nanocomposites.\u201cFiber-Reinforced Polymer Nanocomposites\u201d is a newly open Special Issue of Today, nanomaterials are used in several applications, including composites, packaging, electronic, electrical, structural, energy storage, automotive, filtering, and coating applications, among other 1,2,3,4,43,4,5. Nanomaterials can be classified into natural and synthetic. Nanocellulose, nano-clay, graphene and MXene, carbon nanofibers and nanotubes, silica nanoparticles, and ZnO quantum dots are common nanomaterials used in polymer nanocomposites ,9,10. MoInterestingly, research in the field of fiber-reinforced polymer nanocomposites received a lot of findings that positively contributed to many applications such as biomedical, automotive, electronics, structural materials, packaging ,17,18,19This Special Issue will cover recent advances in the three primary aspects of processing, characterization, and performance. Both synthetic and natural nanomaterials-based composites are welcome. Moreover, this issue is welcomed in several vital aspects, such as the production of nanomaterials, surface and interfacial characterization of its properties, economic feasibility, challenges, and future perspectives in the field of polymer nanocomposites; as a result, current and future literature data can be enriched."} +{"text": "A Corrigendum onA Coronal Landmark for Tibial Component Positioning With Anatomical Alignment in Total Knee Arthroplasty: A Radiological and Clinical Study10.3389/fsurg.2022.847987by Gong, T., Wang, R., Gong, S., Han, L., Yi, Y., Wang, Y., et al. (2022). Front. Surg. 9:847987. doi:\u00a0Incorrect Affiliation**1**. Instead of \u201c** Department of Orthopaedics, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China**\u201d, it should be \u201c** Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China **\u201d. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.In the published article, there was an error in affiliation The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Bacteroidetes (B), Proteobacteria (P), and diversity (D) after BS. Firmicutes (F), B, and the (F/B) ratio was inconsistent, increasing or decreasing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were conducted, compared to before surgery. There was a reduction in the relative proportion of F. Moreover, a higher proportion of Actinobacteria (A) was observed after RYGB was conducted. However, the same was not identified when SG procedures were applied. Genera abundance and bacteria predominance varied according to the surgical procedure, with limited data regarding the impact on phyla. The present study was approved by PROSPERO, under registration number CRD42020209509.Gut microbiota (GM) after bariatric surgery (BS) has been considered as a factor associated with metabolic improvements and weight loss. In this systematic review, we evaluate changes in the GM, characterized by 16S rRNA and metagenomics techniques, in obese adults who received BS. The PubMed, Scopus, Web of Science, and LILACS databases were searched. Two independent reviewers analyzed articles published in the last ten years, using Rayyan QCRI. The initial search resulted in 1275 documents, and 18 clinical trials were included after the exclusion criteria were applied. The predominance of intestinal bacteria phyla varied among studies; however, most of them reported a greater amount of Obesity is a public health problem, and its prevalence has increased in recent decades; this is due, in part, to its multifactorial characteristics, which make it difficult to control ,2,3. It Recently, scientific evidence has proposed the contribution of the gut microbiota (GM) to metabolic alterations and obesity ,3. The GFirmicutes (F) and an increase in Bacteroidetes (B) and Proteobacteria (P) [In the face of the global obesity pandemic, bariatric surgery (BS) has been considered one of the most effective treatments for severe obesity, as well as for long-term weight reduction and maintenance. In addition, the surgical treatment has been proposed as a possible explanation in regard to the observed modifications of the GM composition after surgery ,10,11,12eria (P) ,13. For Search Strategy.A systematic literature review was conducted by two independent reviewers in November 2022, using the PubMed, Scopus, Web of Science, and LILACS databases. The languages were restricted to English, Spanish, and Portuguese. The terms used for the search consisted of \u201cbariatrics\u201d, \u201cgastroplasty\u201d, \u201cbariatric surgery\u201d, \u201cgastric bypass\u201d, \u201cjejunoileal bypass\u201d, \u201cstomach stapling\u201d, \u201cmicrobiot\u201d, \u201cmicrobiome\u201d, \u201cgastrointestinal flora\u201d, \u201cgut flora\u201d, \u201cintestinal flora\u201d, \u201cgastrointestinal microflora\u201d, and \u201centeric bacteria\u201d, using the Boolean operators \u201cAND\u201d and \u201cOR\u201d.Helicobacter pylori; intervention with probiotics, prebiotics, food supplements, and herbal medicines and medications (except in case of antidiabetic drugs).Studies that evaluated the GM profile in obese adults undergoing BS were included. Exclusion criteria were as follows: articles not published in the last ten years, not within the scope of the review, and not written in English, Portuguese, or Spanish; studies carried out in animals, pregnant women, lactating women, adolescents receiving bariatric surgery, and adults with obesity not undergoing BS; experiments with fecal microbiota transplantation, which did not assess the GM profile and without analysis of F and B; chronic noncommunicable diseases, except obesity and type 2 DM, inflammatory bowel diseases, nephropathy with the presence of Two researchers (V.O.R.C. and L.C.) carried out the identification and selection of the studies. They utilized the Rayyan QCRI application/website, with the intent of documenting all inclusion and exclusion decisions, allowing peer review with impartiality and traceability, thus minimizing the risk of bias . After sOutcome Measures.The primary outcome was to verify the occurrence of alterations in the composition of the GM, analyzed by 16S rRNA and metagenomics techniques, after BS. The secondary outcome consisted of changes in anthropometric parameters, including body weight, body mass index (BMI), and the remission of obesity-related diseases, such as type 2 DM. The main aspects of interest for article selection are described in The present study was approved by the public database of protocols for systematic reviews with health outcomes PROSPERO, under registration number CRD42020209509.The applied search strategy returned a total of 1275 published articles, 8 in LILACS, 432 in PubMed, 555 in Scopus, and 280 in Web of Science, between November 2012 and November 2022, of which 518 were duplicates. After screening by title and abstract, as well as the full text when necessary, 18 studies were included in the systematic review, as shown in Relevant data from the studies included in this systematic review are summarized in The studies added to the systematic review and the results of interest are shown in Of the selected studies, 15 out of 18 (83 %) were conducted after an RYGB procedure ,28,30,31The interaction between GM and BS is complex since surgery itself results in anatomical and physiological changes in the intestine. It is a multifaceted condition, where in addition to the surgical modifications, food consumption is altered, and weight loss occurs quickly after surgery, conditions that impact the GM. On the other hand, the GM composition seems to influence the prognosis of weight loss and metabolic improvement ,10,20,32Modifications in the GM after BS have been associated with improved glucose homeostasis, weight loss, changes in food course and motility in the gastrointestinal tract, and changes in nutritional status and diet therapy after BS ,10,26. TRoseburia intestinalis, from phylum F. This increase was also described in other recent studies, regardless of the surgical procedure, associated with a beneficial effect on improved insulin sensitivity, corroborating the hypothesis that alterations in the composition of the GM after BS may be associated with remission of DM. It should be noted, however, that changes in the proportion of phylum F after BS were still heterogeneous in both surgical procedures [Murphy et al. observed a reduction in BMI and type 2 DM remission after one year of both SG and RYGB . Koffer ocedures ,23,30.In obese individuals, GM dysbiosis has been documented, especially towards a greater relative abundance of F and a reduction in B and D, with modifications regarding the quantity and variability of bacterial species. Most studies in the present review corroborated the indication that D decreased with BS. Studies that showed an increase in F, associated this modification with the higher energy and fatty acids uptake and BMI .The literature has shown that a lower F/B ratio is associated with weight loss and metabolic improvement . HoweverThe increase in P abundance, observed in different postoperative periods of RYGB and after six months of SG, may be due to greater transient oxygen exposure and changes in the gut pH as a result of BS . In miceVeillonella, from the F phylum, was higher in only four of the sixteen studies with RYGB, and the same was not observed in the SG procedure [The relative abundance of the genus rocedure ,19,21,25Veillonella. The relative abundance of this bacteria was higher after three months of BS, when compared to the preoperative period, and associated with BMI reduction. The higher proportion of Veillonella may be due to anatomical modifications on stomach size and the oral microbiota composition after surgical intervention and has been linked to the control of inflammation and body weight [In patients undergoing RYGB, a negative correlation was observed between the BMI and five genera of bacteria, including y weight .Akkermancia muciniphila, from the phylum Verrucomicrobia, has been considered to have an anti-obesity effect and enhance type 2 DM remission [emission . This baemission ,18,23,26emission ,25,26. HStreptococcus, the genus of phylum F, had greater abundance in only two of the thirteen studies with RYGB and in one of the nine studies with SG, which may show the survival and proliferation of aerotolerant bacteria [Streptococcus in patients with persistent type 2 DM one year after the surgical procedure, suggesting a positive association between the expansion of this genus of bacteria and the risk of this chronic disease [As for bacteria ,21,27. A disease .Faecalibacterium prausnitzii, despite evidence associating its abundance with reduced plasma glucose levels and increased insulin sensitivity and possible anti-inflammatory effect [y effect ,37, showy effect ,23.Akkermansia muciniphila, Escherichia coli, Bacteroides spp., and bacteria associated with the oral microbiota [In general, RYGB surgery seemed to result in a major modification of the GM composition compared to SG ,31. Thuscrobiota , as obseGM appears to stimulate the immune system and the enteric nervous system, modulating the central nervous system and possibly impacting the hypothalamic signaling of hormones related to hunger and satiety, immune regulation, intestinal motility and secretion, and intestinal mucosal homeostasis. This mechanism of interaction between the GM, the immune system, and the neuroendocrine system has been associated with intestinal permeability, inflammatory state, changes in feeding behavior, and bacterial survival and growth , which cHelicobacter pylori or urinary tract infection, for example), the use of antibiotics in the perioperative phase and supplements, complications after BS, withdrawal of participants during the research, and the use of different surgical procedures and procedures for DNA extraction for analysis of the GM composition [The heterogeneity of data on the impact of BS on the GM, is partly due to the small sample sizes, the lack of information and/or control of dietary intake and gastric pouch size after surgery, studies with only one sex or no information regarding the sex of the study population, and the lack of information on the presence of diseases associated with obesity ,22,25,30position ,17,31. FThe long-term impact of BS on the GM is not yet known, particularly in terms of postoperative follow-up greater than one year, with most studies having up to six months ,28,29,31Actinobacteria (A), P, and D was observed in most studies with no consistency regarding the F/B ratio. After SG, there was an increase in the proportion of B, P, and diversity, with no reports on A or consensus on the F/B ratio. In both surgical procedures, there were reports of a decreased proportion of F. For specific bacteria genera, the literature available is not necessarily the same as for phyla. The magnitude of the modifications on the abundance of bacteria is also unknown.Obesity surgical treatment, such as BS, has a positive impact on lipid and glucose metabolism, remission of type 2 DM, and weight loss and also results in GM changes. In patients undergoing RYGB, an increase in B, The results are controversial, differ according to the surgical procedure, and may change depending on the postoperative period studied; thus, it is not possible to state whether changes in the GM would be permanent. Additionally, the literature available cannot discriminate between whether the GM changes are due to the BS itself and not to the diet and lifestyle modifications that also occur after surgery, for example. For now, it is not prudent to state the magnitude of the influence of changes to the GM, as a contributing factor for weight loss promotion and metabolic improvement after BS."} +{"text": "In \u201cUsing the Transformative Storytelling Technique to Generate Empowering Narratives for Informal Caregivers: Semistructured Interviews, Thematic Analysis, and Method Demonstration\u201d :e36405), one error was noted.In the originally published paper, Affiliation 6 for author Andrea Gaggioli appeared as follows:Applied Technology for Neuro-Psychology Lab, Istituto Auxologico Italiano, Milan, ItalyIn the corrected version of the paper, Affiliation 6 has been revised as follows:IRCCS, Istituto Auxologico Italiano, Milan, ItalyThe correction will appear in the online version of the paper on the JMIR Publications website on September 14, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "The identification of the factors underlying the willingness or lack thereof to respond to public health emergencies is paramount to informing more capable health services. The interest in this topic appears renewed with each surge of threat, either referring to natural disasters, man-made violence, or epidemic and pandemics. However, there is no systematic approach to the research patterns and related main findings concerning individual and contextual determinants. The present article contributes to this theme through a systematic literature review of a sample of 150 articles published in the last 30 years on the subject of willingness and preparedness of health professionals to deal with public health threats. Our findings show that the research is mainly phenomena and contextual driven, responding to whichever emergency threat is more salient in a given period. Geographically, research on this topic is led by USA and China, mostly solely, while European countries invest in collaborations that are more international. Universities, including health institutes and schools, and researchers at hospitals conduct most of the research on the topic. The main research areas are medicine, psychology, and psychiatry. Pandemics, including COVID-19, influenza, and natural disasters, are the phenomena gauging more attention as opposed to terrorism events and biological accidents. The specific role of health professionals within the institution, their belief in ethical duties, preparation training, and concerns regarding infection of self and family are the main variables influencing the willingness and ability to report to work in public health emergencies. The worldwide impact of the COVID-19 pandemic fostered the debate and research on a number of issues that required urgent understanding to face the challenges ahead and mitigate the negative impact of the circumstances. These included, among many others, the effects of public health communication, the citizens\u2019 attitudinal and behavioral dispositions to engage and act in accordance with the governmental measures, the general view and compliance with vaccination programs, teleworking provisions, and related issues concerning work-personal life balance and gendered expectations ) OR (disaster[Title/Abstract])) OR ) OR (COVID-19[Title/Abstract])) AND (willing to work[Title/Abstract])) OR (report to work[Title/Abstract]).No time period was applied, and only publications in English and Portuguese languages were retained, with the exclusion of French and German articles for which we did not have the required language skills to analyze. In addition, errata and letters were excluded.Following these criteria, 206 publications were identified, 131 in the SCOPUS database and 75 in PUBMED, with 37 duplicates that were excluded, resulting in 169 publications. A second reading to determine the eligibility of the publications by titles, keywords and abstracts was made by two independent reviewers, and 18 publications were excluded due to focusing on tangential aspects of the topic under analysis. The final number of publications was 151 selected from the two databases (SCOPUS and PubMed) were saved in bibtex and converted in R in bibliometrix, allowing the analysis of the bibliographic patterns of each publication. More specifically, it characterizes the geographic dissemination of this research as also the authors and institutions that may be specialized in the subject or its specific dimensions, answering to our first goal. A manual and software-based content analysis was conducted. First, the theoretical models, samples, and phenomena were identified manually to answer our second goal. In a second phase, a lexicographic analysis, hierarchical descending cluster analysis, and post-hoc correspondence analysis were conducted using the textual analysis software Iramuteq version 0.6. This software provides the users with different text analyses, either simple ones, such as the basic lexicography , or multivariate ones, such as hierarchical descending analysis, herein used. The hierarchical descending cluster analysis is an iteration method that results in a hierarchy of clusters. The corpus was separated into 150 texts corresponding to the number of abstracts to be analyzed. Nouns and verbs were considered for analysis, as they were suitable to reflect emergent themes and theoretical and methodological aspects. The hierarchical descending cluster analysis retained 512 text segments and 2854 elementary context units (ECUs) from the total of (99.45%). The ECUs are text units within which IRAMUTEQ calculates the frequency of word co-occurrences. The aim of this analysis was to determine the more frequent themes of the research of public health emergencies and interrelated notions, thus meeting our third goal. The vocabulary distribution is presented in a comprehensive and clear way with graphical representations derived from the lexicographic analysis . The maiThe publications related to our search words, including pandemic, disasters, public health emergency, COVID-19, and willingness, as shown in The author with more publications is from the USA and publishes in health sciences, albeit with only three articles ; Table 1As shown in The number of articles\u2019 citations is a suitable indicator of how widespread and disseminated the research is. The analysis was performed using Plum x Metrics, which allows us to see the usage and reads, captures, dissemination in social media, and mentions .The more cited articles focus on capacity needs for health care systems, factors that determine the ability and willingness to contribute during catastrophic events, and those that determine the lack thereof. A common topic among the more cited is ethical professionals\u2019 duty in emergencies that may affect them visa vis the fear of contracting or transmitting to their families the infectious disease at hand. Interestingly, the one more disseminated in social media focuses precisely on perceived barriers to ability and barriers to willingness, concluding that there is an overlapping between both. The need to stimulate both abilities and willingness of health professionals should cThe publication venues are very fragmented, with one journal comprising seven articles, the other three journals encompassing six, five, and four articles, respectively, and the remaining with three or fewer articles published in diversified journals. The more common is specific to disaster research , followed by generalist journals on public health . Reinforcing the scarce publications per author, the wide dispersion of publication venues, with few journals publishing more than three articles on this subject, is also suggestive of the lack of a centralized corpus of research or specialized venue encompassing all the different emergency manifestations and valences. The more frequent disciplinary field is medicine .n = 94) together with other educational institutions, namely health institutes (n = 4) and health schools (n = 6), followed by hospitals (n = 13) and specific medical departments (n = 10).The authors\u2019 affiliations are mostly linked to universities and the pandemic influenza of 2009 and 2010.As shown in The articles researching willingness and preparedness of health professionals during the COVID-19 pandemic correspond to a wide array of geographical contexts, given the worldwide reach of this threat: Palestine , AustralThirty-five other studies refer to other pandemics, particularly influenza virus-based that required special care in health units. These also include several geographical contexts: United States ,109,110,As for natural disasters, ranging from higher to lesser impactful ones, they were conducted mainly in places where these disasters are more common, including Israel , Canada Articles researching the coping of health professionals and the required measures in case of future attacks in the face of terrorist attacks are circumscribed to the U.S. ,118.The main instruments used to collect data were questionnaires, interviews, and, to a lesser extent, focus groups. The questionnaire is employed more often e.g., ,99,114) ,114 99,1Regarding the data analysis patterns, besides descriptive statistics, the more commonly employed are linear and multiple regression analyses. In , the goaThe studies researching socio-demographic factors indicate that older health professionals show less willingness to work in emergency contexts, as do women and health professionals with more family responsibilities, especially small children and, also, pets to take care of e.g., ,80,142).,142.80,1Socio-demographic features and the type of emergency are thus fundamental variables impacting the willingness to report to work in public health emergencies. The radiological and nuclear incidents are the hazards associated with less willingness to report to work ,146 alsoIndividual features of healthcare professionals, including fear, lack of confidence, and uncertainty about safety, are the more systematic variables predicting the willingness to report to work in several types of public health emergencies . Other iOn a supra level, tackling the same need to mitigate the uncertainty brought by a public health crisis is the need for awareness from health professionals to know the steps of the emergency protocol or plan, and tailored changes in the workplace to accommodate pandemic challenges e.g., ,149,150),150149,1The hierarchical descending cluster analysis divided the corpus into 5 clusters distributed as shown in p < 0.01), casualty , radiological , mass , incident , earthquake , nuclear , radiation , terrorist , personnel , management , chemical , victim , biological , guideline , family , terrorism , train , disaster , nonterrorism , smallpox , radioactive , oncology , accident , educational , bomb , preparedness , confidence , need , emergency , safety .Cluster 1, labeled \u201cHigh profile Health hazards\u201d, accounts for 24.68% of our sample and focuses on a wide variety of public health risks and threats caused by natural events or man-made situations. The literature associated with this cluster emphasizes the need for strategic preparedness and readiness of healthcare workers and systems to resiliently deal with these dangerous hazards. It includes the following expressions: event , health , public , worker , local , avian , response , ability , pandemic , department , workforce , universal healthcare , U.K. , surge , ethical , state , system , potential , catastrophic , ill , emergency , global , absenteeism , capacity , unit , ethic , facility , duty , government , behavior , plan flu , employee , numb , clinician , h1n1 , threat .Cluster 2, named \u201cOutbreaks impact on public healthcare system and workforce\u201d (21.56% of our sample), focuses on other diseases that require emergence responses from the healthcare system and workers, namely influenza and H1n1 (avian flu). The articles associated with this cluster emphasize more healthcare public policy provisions alongside specific challenges faced by the healthcare workforce, such as absenteeism. It includes the words influenza , logistic , datum , leadership , questionnaire female woman , peritraumatic , distress , stress , exhaustion , domestic , proportion , disorder , support , collaboration , anxiety , status , intervention , emotional , social , scale , interview , mental .Cluster 3, named \u201cPsychological impacts of emergency work\u201d, accounts for 21.56% of the articles and includes more information on specific statistical analysis and instruments of data collection, but, more importantly, analyzes the psychological consequences of working in emergency situations. These include an allusion to emotional and socially demanding situations for mental health emergencies, including distress, stress, anxiety, peritrauma, and exhaustion, felt particularly by female participants. The concepts more associated with this cluster are regression , stressors , doctor , volunteer , respiratory , medical , coronavirus , education , choice , career , medicine , conclusion , infection , disease , specialty , military , cause , infectious , Chinese , burden , anxiety (\u03c7\u00b2 = 14.69 p < 0.01), syndrome , parent , symptom , educate , satisfaction , depression , decrease , psychological , efficacy , , COVID , cope , stress , fear , expose , worry , emerge science , depressive , exposure , frontline , mental , male , train period .Cluster 4, named \u201cCOVID-19 and medical doctors coping\u201d, includes articles closer to those of cluster 1 also revolving around COVID-19, albeit with a broader range of issues and specific healthcare professions. It accounts for 13.51% of the articles. The emphasis is on students of medicine and medical doctors coping with pandemic COVID-19 stressors in situ and the application of educational and scientific-based approaches to deal with the new challenging outbreak. While Cluster 1 emphasized the burden on nurses, this cluster explores more in depth the psychological impact on doctors. The stronger words associated are student , nurse , China , professional (\u03c7\u00b2 = 21.59 p < 0.01), work , challenge , influence , perspective , willingness , decision , quality , outbreak , frontline , evidence , natural , provider , disease , care , crisis , patient , condition , demand , motivation , commitment , Australian , problem , policy , organizational , Japan , pressure , affect and healthcare . In order to better grasp the contextual meaning of the concepts pertaining to this cluster, we have consulted the typical text segments in which some of the most frequent words appear (using as ranking score the sum of \u03c7\u00b2 = of marked forms in segment).Cluster 5, named \u201cCOVID-19 Outbreak and health providers motivation and commitment\u201d, accounts for 18.7% of the sample, including literature already focused on the pandemic COVID-19, emphasizing notions of urgency and challenging demands and conditions. Although nurses are the specific health professionals more associated with this cluster, more generic mentions of professionals, providers, and organizational contexts are made. Moreover, the focus on health providers considers their motivation, commitment, and willingness, especially those on the frontline. The main geographical contexts are China, Japan, and Australia. The specific words more associated with this cluster are COVID are alongside the specific hierarchical role, the schedule required, and the quality of preparation training. Belief in duty and belief in protecting their family are at the different symbolic and values-based poles of this dilemma. The individual aptitude for working and thriving in an emergency context depends on the individual risk perception and underlying factors, the family support in engaging in that activity, and the required perceived skills to fight the emergence. Naturally, different provisions are required depending on health emergencies, and the response outlining must consider the aptitudes and willingness of health professionals as well as the available resources in the institution . SpecifiThe mindset, as profusely emphasized during times of crises, should be to capacitate health professionals with the best resources possible, including specific training, psychological accompaniment during and after the exposure to the acute or long-standing event, awareness-raising regarding their role and duties, a clear, comprehensive attitude of support to mitigate the feelings of concern or fear regarding one\u2019s or family health. To know the factors and apply contingency measures is halfway through more capable and willing health professionals to deal with threatening situations with the least impact possible on their health in its aftermath."} +{"text": "Silicon carbide nanotubes (SiCNTs) have generated significant research interest due to their potential use in the fabrication of electronic and optoelectronic nanodevices and biosensors. The exceptional chemical, electrical and thermal properties of SiCNTs are beneficial for their application in high-temperature and harsh-environments. In view of the limited thermal stability of carbon nanotubes, they can be replaced by silicon carbide nanotubes in reinforced composites, developed for operations at high temperatures. However, fundamentally theoretical studies of the mechanical properties of the silicon carbide nanotubes are at an early stage and their results are still insufficient for designing and exploiting appropriate nanodevices based on SiCNTs and reinforced composites. In this context, the present study deals with the determination of Young\u2019s and shear moduli of non-chiral single-walled silicon carbide nanotubes, using a three-dimensional finite element model. For nearly two decades, non-carbon nanotubes (N-CNTs) have been the focus of interest for the National Aeronautics and Space Administration (NASA) due to their use in hazardous environments . SiliconSiCNTs were synthesized for the first time by Sun et al. , who conThe reinforcement of composites for machinery parts by CNTs significantly improved their performance and helped to reduce the weight of its components. Nevertheless, this may not meet the requirements for numerous applications, such as high-temperature and high-power electronics, systems with improved thermal conductivity and nanodevices operating at high temperatures and in harsh environments. SiCNTs with optimum thermal properties, high conductivity and promising prospects for mass production can be suitable candidates to replace the CNTs. However, the silicon atom, Si, has a larger atomic radius, lower electronegativity and weaker bonds, which leads to properties of SiCNTs that are different from those of CNTs . RegardiOn atomistic approaches, in the work by Baumeier et al. , the surWith regard to the CM approach, where the whole nanotube is replaced by a single continuum structure, Mercan and Civalek analyzedIn contrast to CM, the NCM/MSM approach considers the bonds between Si and C atoms as elastic beams, making use of the connection between the nanotube molecular structure and solid mechanics. Genoese et al. evaluateThe goal of this study is to assess the Young\u2019s and shear moduli of non-chiral single-walled silicon carbide nanotubes (SWSiCNTs) with chiral indices and diameters in a broad range, making use of the NCM/MSM approach, which employs beam elements. So far, the NCM/MSM approach is the most commonly indicated for effective and fast computational simulation of the N-CNTs mechanical response. To this end, a three-dimensional numerical model was used, which allowed the determination of bending, tensile and torsional rigidities, and, afterwards, the calculation of the elastic moduli of SWSiCNTs.hC, and the chiral angle, \u03b8, given by the following expressions, respectively:As shown in The SiC sheet can be rolled up into a cylinder in different ways, varying the chiral angle, \u03b8, from 0\u00b0 to 30\u00b0 see, , formingc, and the diameter, NTs are characterized by the nanotube circumference, L0.177 nm , 0.179 n0.177 nm and 0.180.177 nm .bAb, bending, EbIb, and torsional, GbJb, rigidities of beam elements, constituting the equivalent continuum structure, and the bond stretching, kr, bond bending, k\u03b8, and torsional resistance, k\u03c4, force constants, which describe the molecular structure:l is the beam length.The nanoscale continuum modelling/molecular structural mechanics approach was used, which substitutes the Si\u2013C bonds of SWSiCNTs by equivalent beam elements. Li and Chou establisl, and the bond length, Thus, Equation (5) is the basis for the analysis of the elastic behaviour of SWSiCNTs, using the link between the continuum and molecular mechanics, which together with the assumption of equivalence between the beam length, FE model .\u00ae . To transform the program database files, provided by the Nanotube Modeler\u00a9 software, to a format suitable to be used in the commercial ABAQUS\u00ae code, the home programme InterfaceNanotubes.NM was used [The FE models of the SiC nanotubes use the coordinates of the Si and C atoms to create the nodes and the appropriate connections between the nodes to generate the beam elements. The respective meshes were constructed using the Nanotube Modeler\u00a9 software , which produces program database files. These files contain the atom positions and interatomic connections, which serve as input to FE\u2019s commercial code, ABAQUSwas used . Table 2\u00ae. Therefore, in the respective conventional tests, the transverse force, Ft, the axial tensile force, Fa, and the torsional moment, T, were applied to one edge of the NT, while the other edge is constrained. To carry out the torsion test, the loaded nodes were prevented from moving in the radial direction.The mechanical behaviour of SWSiCNTs under numerical bending, tensile and torsion tests was studied with to the FE code ABAQUSa, the transverse displacement, ut, and the twist angle, \u03c6, are obtained from the FE analysis of the tensile, bending and torsion tests, respectively. Consequently, the tensile, EA, bending, EI, and torsional, GJ, rigidities of the SWSiCNTs can be determined as follows, respectively:n is the NT\u2019s length.The axial displacement, uAs for the single-walled carbon ,27, boroKnowing the EA and EI rigidities and using Equations (9) and (10), the diameter Subsequently, replacing the mean diameter, As in the case of most N-CNTs , there in, several authors have chosen to report the values of the surface Young\u2019s and (14), requires reliable knowledge of the value of tThe viability of Equations (15) and (16), to be used to evaluate the The tensile, EA, bending, EI, and torsional, GJ, rigidities of non-chiral SWSiCNTs, from (SWCNTs) ,27, the (SWCNTs) , and the(SWCNTs) , for non[Dn see, b, and thAs previously established by the authors for the SWCNTs ,27, SWBNIt is worth noting that the linear function presented by Equation (19) and the cubic functions expressed by Equations (20) and (21) can be comprehended based on the quasi linear relationship of the cross-sectional area, A (Equation (9)), and the cubic relationships between the moment of inertia, I (Equation (10)), and the polar moment of inertia, J (Equation (11)) with the nanotube diameter, respectively.To investigate the accuracy of the aforementioned analytical expressions for the evaluation of the three rigidities, Substituting, in Equations (15)\u2013(18), the tensile, EA, bending, EI, and torsional, GJ, rigidities by the respective expressions (19)\u2013(21), and knowing the parameters As a result, Equations (22)\u2013(25) allow the assessment of the SWSiCNTs elastic moduli without resorting to numerical simulation.First, the results of the non-chiral SWSiCNTs Young\u2019s modulus, calculated with Equations (13) and (22), for three different values of the NT wall thickness, ter see, . It shouThe results related to the effect of the nanotube wall thickness, It can be concluded that the Young\u2019s modulus, E, decreases when the wall thickness, u et al. , the val nm see, a. Thus, As there is no reported accurate value of o 0.6 nm a,b. For ess see, a,b. FromThe results presented in The surface Young\u2019s modulus, 24) see, a. The la8 TPa\u00b7nm which arr et al. , using ar et al. , who empr et al. and Jianr et al. are at ar et al. , calculaEquation in the prk of Le and Jianrk of Le . Despiterk of Le and Jianrk of Le sharing rk of Le reportedrk of Le , most liThe discrepancy of the In this section, the results of the shear modulus, G, and the surface shear modulus, e et al. .n = 0.34, 0.39, 0.45 nm.The shear modulus, G, of the non-chiral SWSiCNTs increases for NT diameters, Similar to the case of the surface of the Young\u2019s modulus, the non-chiral SWSiCNTs surface of the shear modulus, The nm see, a,b. ThusThe As can be seen from The average value to which the surface of the shear modulus of the non-chiral SWSiCNTs converges is approximately 36% lower than that evaluated for the SWCNTs. This should be taken into account in the design and construction of NTs-based devices and systems, where SiCNTs are considered a replacement for CNTs. Regarding the e et al. . Reasonae et al. reportedses see, . Howevere et al. , which ue et al. assumed The Young\u2019s and shear moduli of non-chiral SWSiCNTs were assessed using numerical simulation, based on the NCM/MSM approach. The main achievements of the present study are presented in the following paragraphs.Equations establishing the relationship between each of the three rigidities\u2014tensile, bending and torsional\u2014and the NT diameter were obtained. The fitting parameters of Equations (19)\u2013(21), which permit the assessment of the rigidities of the SiC nanotubes\u2014regardless of the symmetry group: zigzag or armchair\u2014were calculated. In this way, the previously established method for calculating the three rigidities without resourcing to numerical simulation, is extended to silicon carbide NTs.The evolutions of the Young\u2019s modulus with the nanotube wall thickness were used to make assumptions regarding the realistic value of The accuracy of Equations (17) and (18), for the evaluation of the surface of the Young\u2019s and shear moduli, respectively, was demonstrated. In our view, these equations are suitable to calculate the surface of the Young\u2019s and shear moduli of the N-CNTs, for which there is no appropriate value of the NT wall thickness reported in the literature.The results obtained contribute considerably to a benchmark in the evaluation of the elastic constants of the silicon carbide nanotubes by theoretical methods."} +{"text": "Magnetic Functional Materials: Synthesis, Characterization and Application is a new open Special Issue of Materials, which aims to publish original and review papers on new scientific and applied research, and make great contributions to the finding and understanding of magnetic functional materials and related synthesis, fundamentals, characterization, and applications.The early magnetic materials were mainly silicon steel and ferrite. Since the 1960s, a series of high-performance magnetic functional materials such as amorphous soft magnets, nanocrystalline soft magnets and rare-earth permanent magnets have appeared one after another [In the contemporary information society, energy, information, and materials are the important foundation of production, life, and high technology. Magnetic functional materials are widely used in energy, information, and materials science and technology. There are many kinds of magnetic functional materials, and their progress is rapid. Magnetic functional materials have attracted a great deal of attention regarding their applications. Magnetic behaviors are widespread in a variety of materials, such as metals, ceramics, organics, and emerging 2D materials. Applications of magnetic materials include memories, sensors, magnetic refrigeration, drug delivery, electrochemistry, environmental protection, energy storage, and more.Magnetic Functional Materials: Synthesis, Characterization and Application includes, but is not limited to, the following: permanent magnets; magnetic functional materials; magnetism in correlated electron systems; memories and sensors devices; magnetic refrigeration; environmental protection; and devices based on magnetic materials.The research interest of the section"} +{"text": "Instead of \u201cDepartment of Pharmacy Practice,\u201d it should be \u201cDepartment of Clinical Pharmacy.\u201dIn the published article, there was an error in affiliation Ohoud S. Almalki was mistakenly not credited as a contributing author in the original Author Contributions. The Author Contributions Statement previously stated:OSA and OAA: conceptualization and project administration. OAA: methodology, software, data curation, formal analysis, and funding acquisition. OSA and MA: validation and writing\u2014original draft preparation. OSA, OMA, and MA: investigation. YA, OMA, and OAA: writing\u2014review and editing. OMA, MA, and YA: visualization. OSA, YA, and OAA: supervision. All authors have read and agreed to the published version of the manuscript.The corrected Author Contributions Statement appears below.OSA and OAA: conceptualization and project administration. OAA: methodology, software, data curation, formal analysis, and funding acquisition. OSA and MA: validation and writing\u2014original draft preparation. OSA, OMA, and MA: investigation. YA, OMA, and OAA: writing\u2014review and editing. OMA, MA, and YA: visualization. OSA, YA, and OAA: supervision. All authors have read and agreed to the published version of the manuscript.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The American Journal of Gastroenterology published a series of reviews by a Rome Foundation Working Group on the emerging role of food in the pathogenesis, illness experience, and treatment of what were then referred to as Functional Gastrointestinal Disorders (FGIDs) . At the (FGIDs) \u20139.Over the ensuing 9 years, our thinking about FGIDs has expanded and evolved. We have an enhanced understanding of the complexity of the pathophysiology of these conditions. Reflecting this, the Rome Foundation has proposed a change in the label applied to FGIDs, which for many had become a 4-letter word. The new label, Disorders of Gut-Brain Interaction (DGBI), retains a 4-letter abbreviation but one that is intended to be more descriptive and less negatively charged for patients and providers .One of the most important advances in our understanding of DGBI involves the interaction between the gut luminal microenvironment and the host . Among tAJG manuscript series published in 2013, we posited, \u201cfood is complex.\u201d These words ring even more true in 2022 (In the introduction to the in 2022 . It is pAJG for enabling the dissemination of the work of this Rome Foundation Working Group. We also extend our heartfelt gratitude to the authors for their hard work and dedication to this project. We hope that in the menu of offerings, you find information that suits your fancy. Bon Appetit!We thank the editors of Guarantor of the article: William D. Chey, MD.Specific author contributions: All authors participated in the conception, preparation of the first draft, critical revision of subsequent drafts, and approval of the final article.Financial support: None to report.Potential competing interests: W.D.C. is a consultant for AbbVie, Allakos, Alnylam, Ardelyx, Arena, Bayer, Biomerica, Ironwood, Nestle, QOL Medical, Salix/Valeant, Takeda, Urovant Sciences, and Vibrant; has received grant and/or research study funding from Biomerica, Commonwealth Diagnostics International, QOL Medical, and Salix; has stock options in GI on Demand, Modify Health; serves on the Rome Board of Directors; and is a member of the Board of Trustees of the American College of Gastroenterology and Board of Directors of the International Foundation for Gastrointestinal Disorders. J.T. is a consultant for Adare, Alfa Wassermann, Arena, Bayer, Christian Hansen, Clasado, Danone, Devintec, Falk, Gr\u00fcnenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neurogastrx, Neutec, Novartis, Nutricia, Ricordati Shionogi, Takeda, Truvion, Tsumura, Zealand, and Zeria pharmaceuticals; has received research support from Biohit, Shire, Sofar, and Takeda; and has served on the speaker bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Wellspect, and Zeria and is President of the Rome Foundation."} +{"text": "Given that dental practice is currently based on the \u201caverage\u201d patient, providing therapeutic and rehabilitative interventions rather than preventive measures , with liP4 medicine, including precise , personalized , preventive (early detection and intervention), and participatory (directly involving patients) approaches, is based on a deeper understanding of the etiology and course of oral disease and, in particular, the broader social, behavioral, and systemic determinants of oral health and its relationship to overall health .Therefore, the increasing integration of P4 medicine principles into oral care should favor the transition from \u201creactive\u201d disease-waiting dentistry with standardized protocols to \u201cproactive\u201d approaches that track patients\u2019 parameters in a way that is as comprehensive, continuous, and prompt as possible [In recent decades, strategies for P4 medicine have been developed, supported by digital technologies (including software and devices for data computation and storage) and medical data systems , primarily to predict what will happen to a patient or a particular organ or site [In oral, dental, and periodontal care, predicting the case-specific development of caries or perioIn addition, predicting the site-specific activity and progression of caries and periodontitis could support early-treatment decisions and more accurate, effective, and definitive approaches, with a positive impact on the thorough treatment of patients and their well-being .Moreover, with the proliferation of technology and teledentistry , it is nTeledentistry platforms and tools are increasingly used for consultations with urgent oral and dental needs and concerns, as well as for telediagnoses, especially for the elderly, the frail, and those living in remote areas ,13,14,15Smartwatches, smartphones, and tablets are increasingly becoming an integrated part of our approach to health. M-health applications enable the progression of caries lesions and the progress of orthodontic treatment to be monitored, reinforce biofilm control and provide support and guidance for post-surgical courses .Furthermore, teledentistry and M-health, in combination with widely used smart sensors on the one hand and artificial intelligence and machine learning on the other, may foster the development of next-generation systems ,17 for a"} +{"text": "While of predominant abundance across vertebrate genomes and significant biological implications, the relevance of short tandem repeats (STRs) to speciation remains largely elusive and attributed to random coincidence for the most part. Here we collected data on the whole-genome abundance of mono-, di-, and trinucleotide STRs in nine species, encompassing rodents and primates, including rat, mouse, olive baboon, gelada, macaque, gorilla, chimpanzee, bonobo, and human. The collected data were used to analyze hierarchical clustering of the STR abundances in the selected species.We found massive differential STR abundances between the rodent and primate orders. In addition, while numerous STRs had random abundance across the nine selected species, the global abundance conformed to three consistent\u2009<\u2009clusters>, as follows: , , and\u00a0, which coincided with the phylogenetic distances of the selected species (p\u2009<\u20094E-05). Exceptionally, in the trinucleotide STR compartment, human was significantly distant from all other species.Based on hierarchical clustering, we propose that the global abundance of STRs is non-random in rodents and primates, and probably had a determining impact on the speciation of the two orders. We also propose the STRs and STR lengths, which predominantly conformed to the phylogeny of the selected species, exemplified by (t)10, (ct)6, and (taa4). Phylogenetic and experimental platforms are warranted to further examine the observed patterns and the biological mechanisms associated with those STRs. Speciation is the evolutionary process by which populations evolve to become distinct species. Several models and theories have been proposed for this highly complicated process, including gene regulatory networks, community ecology, and mating preferences (for a review see ). NaturaSTRs are a source of rapid and continuous morphological evolution, for exaWhile a limited number of studies indicate that purifying selection and drift can shape the structure of STRs at the inter- and intra-species levels \u201322, the Mononucleotide and dinucleotide STRs are the most common categories of STRs in the vertebrate genomes, 24. In Here, we analyzed the global hierarchical clustering of all types of mono-, di-, and trinucleotide STRs in nine mammalian species, encompassing primates and rodents, Those species belong to the superordinal group of Euarchontoglires , and forhttps://hgdownload.soe.ucsc.edu) was used to download and analyze the latest genome assemblies of nine species as follows (genome sizes are indicated following each species): rat (Rattus norvegicus): 2,647,915,728, mouse (Mus musculus): 2,728,222,451, gelada (Theropithecus gelada): 2,889,630,685, olive baboon (Papio anubis): 2,869,821,163, macaque (Macaca mulatta): 2,946,843,737, gorilla (Gorilla gorilla gorilla): 3,063,362,754, chimpanzee (Pan troglodytes): 3,050,398,082, bonobo (Pan paniscus): 3,203,531,224, and human (Homo sapiens): 3,099,706,404. Those species encompassed rodents: rat and mouse, Old World monkeys: gelada, olive baboon, macaque, and great apes: gorilla, bonobo, chimpanzee, human.The UCSC genome browser (https://github.com/arabfard/Java_STR_Finder). All possibilities of mononucleotide motifs, consisting of A, C, T, and G, all possibilities of dinucleotide motifs, consisting of AC, AG, AT, CA, CG, CT, GA, GC, GT, TA, TC, and TG, and all possibilities of trinucleotide motifs, consisting of AAC, AAT, AAG, ACA, ACC, ACT, ACG, ATA, ATC, ATT, ATG, AGA, AGC, AGT, AGG, CAA, CAC, CAT, CAG, CCA, CCT, CCG, CTA, CTC, CTT, CTG, CGA, CGC, CGT, CGG, TAA, TAC, TAT, TAG, TCA, TCC, TCT, TCG, TTA, TTC, TTG, TGA, TGC, TGT, TGG, GAA, GAC, GAT, GAG, GCA, GCC, GCT, GCG, GTA, GTC, GTT, GTG, GGA, GGC, and GGT were analyzed.The whole-genome abundance of mononucleotide STRs of \u2265\u200910-repeats, dinucleotide STRs of \u2265\u20096-repeats, and trinucleotide STRs of \u2265\u20094-repeats were studied in the nine selected species. To that end, we designed a software package in Java STRs. The algorithm started from an initial point, which was the first nucleotide of each genome, and iteratively repeated a series of steps during walking on the genome, nucleotide by nucleotide. In the first step, it investigated a window frame of 2*N, where 2 was the definition of tandem repeats i.e., two identical continuous sequences, and N was the length of the STR core. If the first half of the sequence inside the window was not equal to the second half, the algorithm moved one nucleotide forward. If equal, the algorithm checked the nucleotides, and this process continued until all identical continuous nucleotides, which were the same as the core were found. The final selected sequence- M*N- was introduced as a new STR, which had a core with a length of N and M repeats. All steps were repeated to find new STRs from the end of the previous STR. We repeated the algorithm for different values of N .Whole-genome chromosome-by-chromosome data were aggregated and analyzed in the nine species. STR abundances across the selected species were obtained and depicted by boxplot diagrams and hierarchical clustering, using boxplot and hclust packages in R, reThe STR abundances across the nine selected species were compared by repeated measurements analysis, using one and two-way ANOVA tests. These analyses were confirmed by nonparametric tests.Whole-genome data was collected on the abundance of mononucleotide STRs across the nine species Table\u00a0. We founThe whole-genome STR abundances from aggregated chromosome-by-chromosome analysis in the dinucleotide category Table\u00a0 was decrThere was global shrinkage of the trinucleotide STR compartment in primates versus rodents P\u2009=\u20093.8E-05) 10, (at)8, and (ttg)4 Fig.\u00a0. HierarcWhile the mechanisms underlying speciation are extremely complicated and largely based on theories and models, the impact of genetics seems to be significant in respect of adaptation, gene flow, and natural selection. In fact, natural selection may be a central converging point of the evolutionary propositions for speciation. However, the various mechanisms involved in speciation have different impact on natural selection, and it is the net effect which may ultimately result in the emergence of a new species.As one of the most abundant genetic elements in various animal genomes, it is largely unknown whether at the crossroads of speciation, STRs evolved as a result of purifying selection, genetic drift, and/or in a directional manner.Here, we selected multiple species across rodents and primates, and investigated the clustering patterns of all possible types and lengths of mononucleotides, dinucleotide, and trinucleotide STRs on the whole-genome scale in those species. Hierarchical clustering yielded clusters that predominantly conformed to the phylogenetic distances of the selected species. Hierarchical clustering is an unsupervised clustering method that is used to group data. This algorithm is unsupervised because it uses random, unlabeled datasets. As the number of clusters increases, the accuracy of the hierarchical clustering algorithm improves.http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3) [https://figshare.com/articles/figure/STR_Clustering/17054972). The concept of various TF sets stands for other STRs as well. For example, (ct)6 conforms to the phylogenetic clusters, and recruits a number of TFs, whereas (ct)7, which does not conform to those clusters, recruits quantitatively different set of those TFs . Those vMononucleotide STRs impact various processes, such as gene expression, translation alterations, and frameshifts of various proteins, which may have evolutionary and pathological consequences, 25. TheIn a number of instances, dinucleotide STRs located in the protein-coding gene core promoters have been subject to contraction in the process of human and non-human primate evolution. A numbeTrinucleotide STRs are predominantly focused on in human because of their link with several neurological disorders\u201345. We fThe observed abundances were independent of the genome sizes of the selected species. For example in the instances of di- and trinucleotide STRs, we observed higher abundances in rodents versus primates despite the smaller genome sizes of the former. These findings are in line with the previous reports of lack of relationship between genome size and abundance of STRs, 47.It should be noted that this is a pilot study based on hierarchical clustering, and future studies are warranted to further examine our hypothesis, using phylogenetic platforms and additional orders and species. Functional studies are also warranted to examine the biological impact of the relevant STRs.We propose that the global abundance of STRs is non-random across rodents and primates. We also propose the STRs and STR lengths, which predominantly conformed to the phylogenetic distances of those species, such as (t)10, (ct)6, and (taa4). Additional species encompassing other orders and phylogenetic platforms are warranted to further examine this proposition.This research was a pilot study based on hierarchical clustering of the collected data in a number of mammalian species. Phylogenetic platforms and additional orders of species are warranted to further examine our hypothesis."} +{"text": "Santa Cruz da Prata was a tiny land between the mountains, close to the sky, in the south of the state of Minas Gerais (MG), Brazil. Also known as \u201cPratinha,\u201d this region was once very beautiful, with sierras after sierras and woodlands with the Atlantic trees of Peroba, Jacarand\u00e1, Angelim, Angico, Ip\u00eas, and Sapucaias and all thousands of birds.But there was a time when the coffee planters came; then, one by one, almost all trees were felled and, nowadays, very little, hardly anything, remains. What remained were those empty fields, the coffee plantations dominating a depleted landscape, outlining their dull uniformity. But, even today, when Spring arrives and the rains of September make the first buds bloom from the earth, the fields turn green and those magical mountains take over the silences and mysteries of MG.It was there that, around 1930, Jo\u00e3o Biela da Silva, a respectable citizen and pharmacist, married Gentil Gianerini Silva, and they had five children: Ant\u00f4nio, Ald\u00e9rico, Augusta, Alcino, and Ana Maria. To be more exact, our story begins on February 11, 1936, the date on which he, Alcino, was born.Grande Sert\u00e3o: Veredas, 1956, free translation): \u201cYou will please excuse this bad habit of mine. [...] I don\u2019t know how to tell things straight. [...] Telling something is a very, very difficult business. Not because of the years that have gone by, but because certain things of the past have a way of changing about, switching places.\u201dIt is difficult to distinguish history from story. Everything gets mixed up and combined after so many years that have gone. That is why I would like you to exempt me from eventual failures. As well stated by the Brazilian writer Jo\u00e3o Guimar\u00e3es Rosa , where Alcino completed his elementary education; then, the family moved to Mococa, in the northeast of the state of S\u00e3o Paulo, where he studied the first 2 years of high school education. As if the starts have aligned, once his vocation for Medicine was defined, he moved to Belo Horizonte (MG), where he completed high school at Col\u00e9gio Marconi. Henceforth, he took the admission exam at the two Schools of Medicine then existing and was approved in both. He chose the Federal University , indisputably of better quality at the time, and began his brilliant career in Medicine in 1954. Ever since, and especially since his graduation in 1959, his life as a doctor, surgeon, and professor was an example to be followed. It translates into the nonconformity of a man who did everything to honor his profession and dignify it to the fullest extent. His connection with Prof. Jo\u00e3o Baptista de Resende Alves, then Full Professor of Surgical Technique and Experimental Surgery, from the fourth year of medicine onward, marked his academic and professional training, in such a way that, very early, he was endowed with the characteristics to become the natural heir of the direction of this exemplary surgical school.His stay in the municipality of Entre Rios de Minas lasted 7 years. There, together with his classmate Paulo Silva, he carried out one of the most beautiful works of all known to date. I made a point of personally visiting the city and the Cassiano Campolina Hospital, where he worked. I noticed, by listening to the testimonies of several people, that he did everything there: he organized the maternity ward, guided pregnant women, trained paramedics, provided free health care to the humble, plastered legs and arms, performed operations, and worked. The people there were grateful and granted him the honorable title of honorary citizen.But his horizons were broader. Since then, even though he was settled in a small city, Professor Alcino would come to Belo Horizonte on weekends and spend hours on end at the Surgical Technique Laboratory, working on his doctoral dissertation, brilliantly defended in 1965.At that time, he had already married Ana Maria, his wife, partner, friend, and his backbone for such an ambitious life project. Moreover, Ana gave him his greatest gifts: her love and their seven children.. It is also worth mentioning his efficient tenure as the president of the Brazilian College of Digestive Surgery (1997/1998), as the president of the Foundation for Research and Teaching in Surgery (FUPEC), at the Board of Directors of Hospital Borges da Costa, and the Brazilian Society for Surgery Research Development (SOBRADPEC), where he was the director. He was also, with all and indisputable merits, a member of the Minas Gerais Academy of Medicine and the National Academy of Medicine. He also received numerous honors such as the Grande Medalha da Inconfid\u00eancia , Grande Medalha do M\u00e9rito da Sa\u00fade , and Medalha da Ordem do M\u00e9rito Legislativo , in addition to the honorable title of Honoris Causa Professor of Escola Superior da Santa Casa de Miseric\u00f3rdia de Vit\u00f3ria . It is impossible for me not to say anything before his innovative and creative spirit, when devising surgical techniques that are now recognized worldwide, such as the proposal for the surgical correction of incisional hernias (Alcino Lazaro da Silva\u2019s Technique). Finally, I cannot help but list the dozens of theses that the Professor has so wisely advised, the Digestive Surgery Service of Hospital das Cl\u00ednicas, UFMG, which he created, among so many other activities.I do not intend here to enumerate the Professor\u2019s achievements and innumerable titles. The list is endless and the mission would be impossible in such a small space. So, as summarized as it could be, it would not do justice. However, as a matter of conscience, I feel obliged to report, through and through, some of his achievements since his definitive transfer to the University where he achieved the highest of all titles, that of Professor Emeritus. We should mention his hundreds of published works, his countless books, his brilliant civil service competitive examination for full professor in 1975, his extraordinary teaching participation, the creation of the Graduate Program in Surgery at the School of Medicine of Universidade Federal de Minas Gerais (UFMG), the coordination of numerous disciplines of undergraduate and graduate programs, and the countless honors received either as a sponsor lecturer or as a sponsoring professor of the classes.When he was the president of the Brazilian College of Digestive Surgery (1997/1998), he was responsible for acquiring its own headquarters. In addition, he was the one who included the Latin sentence \u201cUT OMNES UNUM SINT,\u201d which means \u201call for one,\u201d in the College\u2019s symbol, which has been maintained to this dayWords of aggrandizement and praise are usually a habit of those who greet the honoree. In my case, the praise is not just protocol-like: it is much rather a superior commandment of affection and recognition. Our points of view, at times divergent, have only increased my admiration, stimulated by my growing conviction of his greatness of character. Therefore, I allowed myself to trace his paths to show the saga of a man a little, as a humble and unnecessary attempt to frame him in the gallery of the great names of Brazilian surgery. Hence, I entered his backyards, wandered through his father\u2019s pharmacy, tasted the flour cookies and guava sweets made by Jovita, a black mother, who today has a seat in heaven. I participated in his experiments in surgical technique, performed surgeries in Entre Rios, and scoured his enviable and immense curriculum, without any purpose.Grande Sert\u00e3o: Veredas, 1956, free translation):At the end of my text, I sought to understand a fact that, at first, no one could answer me. I redoubled my efforts in tracing his steps, seeking to unravel his option to transfer to Belo Horizonte. I wondered why someone, living in the south of MG, near the border of S\u00e3o Paulo, and who, already studying in that state, decides to go to the capital of MG to study Medicine when, in those times, the most reasonable thing would be to choose the capital of S\u00e3o Paulo. I applied myself, with no support, to the search for this answer, so as to investigate and speculate on his life in a more accurate and competent way. Soon, that is what I found. I found the answer myself by knowing him, by tracing the enchanted universe of Guimar\u00e3es Rosa (Guimar\u00e3es Rosa, Those who are born in Minas Gerais are shy, benevolent, contained, suspicious, disciplined, discreet, scrupulous, thrifty, balanced, faithful, grateful, honorable, intelligent, honest, loyal, meditative, modest, obstinate, prudent, patient, mundane, sensible, without any haste, sagacious, sober, hardworking, timid, virtuous. People born in Minas Gerais bring more individuality than personality, they think that what matters is to be and not to appear, they know that to be agitated is not to act. Those born in Minas Gerais do not dispute. They have no visible audacity. They transcend it. They do not believe that anything can be solved by a gesture or an act, but they have learned that things come back, that life changes, that everything can come back.When it dawned on me, I realized that Prof. Alcino had the face of MG and that there, only there, could he belong. In 2022, now enchanted, he left us a legacy that is difficult to fulfill.Minas, our dear Minas, the \u201clittle homeland\u201d of general stars.Minas that comprises many: Jequitinhonha, Mata, Tri\u00e2ngulo, Metal\u00fargica, Minas do Sul, and Minas of the western hills. Minas from all these cities, from Diamantina, Ouro Preto, Sabar\u00e1, Cordisburgo, Lassance, Montes Claros, Entre Rios, Guaran\u00e9sia, and Santa Cruz do Prata. Minas from Belo Horizonte.Minas crossed by these rivers of deep waters, namely, the S\u00e3o Francisco, Grande, Doce, Paracatu, Carinhanha, Pandeiros, and the green-bluish Urucuia River, love of mine.Minas that God carved and decorated with all the stones \u2014 the sapphires, tourmalines, amethysts, topaz \u2014 these golds of emerald hopes.Minas, mountains, and sky and those mountain paths where Buriti trees touch the clouds.Our Minas, ours alone. Minas of all Brazilians.Minas that gave Brazil most of its greatest geniuses: Drumond, poet; Guimar\u00e3es Rosa, the greatest of all writers; Santos Dumont who, one day, dreamed of flying like birds and did so; Carlos Chagas, the greatest scientist, who single-handedly discovered and fully described a disease; Pel\u00e9, who enchanted the world with his art; Tiradentes who, one day, died to free Brazil. Minas of Juscelino, Milton Campos, M\u00e1rio Palm\u00e9rio, Hilton Rocha, Alfredo Balena, Baeta Vianna, and Jo\u00e3o Baptista de Resende Alves.Minas of Alcino L\u00e1zaro da Silva."} +{"text": "To the Editor: Lewis et al. recommend considering hand, foot, and mouth disease (HFMD) as a differential diagnosis for monkeypox on the basis of a series of 9 patients from Argentina and Bolivia with suspicion of monkeypox, of which 3/9 patients had laboratory-confirmed monkeypox and 4/9 patients had HFMD . Two days before, he began experiencing myalgias and fever, followed by a generalized rash with painful pustular lesions on the arms, hands, feet, mouth, scalp, and anus . He was We swabbed anal, oral, and skin lesions and assessed the specimens for orthopoxvirus and enterovirus nucleic acids by PCR, which was positive for enterovirus but negative for orthopoxvirus, confirming HFMD. In conclusion, we support the suggestion to consider atypical HFMD as a differential diagnosis of monkeypox."} +{"text": "Rubella virus (RuV) generally causes a mild infection, but it can sometimes lead to systemic abnormalities. This study aimed to conduct a bibliometric analysis of over two decades of RuV research. Medical studies published from 2000 to 2021 were analyzed to gain insights into and identify research trends and outputs in RuV. R and VOSviewer were used to conduct a bibliometric investigation to determine the globally indexed RuV research output. The Dimensions database was searched with RuV selected as the subject, and 2500 published documents from the preceding two decades were reviewed. The number of publications on RuV has increased since 2003, reaching its peak in 2020. There were 12,072 authors and 16,769 author appearances; 88 publications were single-authored and 11,984 were multi-authored. The United States was the most influential contributor to RuV research, in terms of publications and author numbers. The number of RuV-related articles has continued to increase over the past few years due to the significant rubella burden in low-income nations. This study will aid in formulating plans and policies to control and prevent RuV infections. Rubivirus genus in the Matonaviridae family [Rubella virus (RuV) is an RNA virus and a member of the e family . It has e family ,3. Althoe family ,5. Approe family . RuV is e family .When infection occurs within the first eight weeks of pregnancy, RuV can have tragic and severe deleterious effects on the fetus, including malformations, premature delivery, and miscarriage . Fetal mBibliometrics is a valuable tool for studying the scientific literature and output through the application of mathematical, statistical, computational, and other methodologies to help extract useful information . BibliomA bibliometric analysis was conducted in this study to considerably increase the quality of the literature review by offering a transparent, systematic, and repeatable review method. It allows for mapping study domains and influential work without subjectivity, which is essential for a holistic approach to the literature review process. The use of statistical and mathematical tools to analyze books and media communications is known as bibliometric analysis. Biblioshiny is a web-based application that provides a user interface for Bibliometrix for non-programmers. It facilitates researchers\u2019 usage of Bibliometrix\u2019s key features. To conduct a bibliometric analysis, various databases are available; each database has distinct characteristics and can offer various features. The most frequently used literature databases are PubMed and Dimensions, both of which are free. However, Web of Science and Scopus cover almost all disciplines, but are only available as subscription databases. Based on sources, authors, documents, and clustering by coupling, analytics and graphs are generated for four distinct levels of metrics. The three K-structures of knowledge can be analyzed using conceptual, intellectual, and social structures. R Studio was initially used to install and load the Bibliometrix R package. By typing Biblioshiny into the R terminal, the Biblioshiny application was started. A number of tools made available by Bibliometrix enable investigators to conduct comprehensive bibliometric analyses ,19,20,21The bibliometric analysis was performed with RuV-centered research from 1 January 2000 to 31 December 2021. Articles from Dimensions were retrieved and evaluated using visualization tools Biblioshiny and VOSviewer .In this study, a standardized search approach was used for the bibliometric analysis based on the inclusion of the keyword \u201crubella virus\u201d in the title, abstract, and keywords. The rubella virus data were collected from January 2000 to December 2021. The analysis included all related original articles, reviews, editorials, and research letters containing the keywords; however, abstracts, communications, and errata/corrections were excluded from the study. To avoid any bias in data collection, two independent investigators (Hafiz Muhammad Zeeshan and Fahad Ahmad) collected data on the same day as the search. After a conversation with a third investigator (Hasan Ejaz), the differences were discussed and resolved. The title of the article, authors\u2019 names, times cited, citations per document, most-cited papers, year of publication, type of paper, countries/regions, institutions/organizations, and journal name were evaluated from the retrieved data.As this study analyzed previously published research, no ethical approval was required. None of the authors of the studies included were contacted for more information about their respective publications.The analysis was performed on a Lenovo Mobile Workstation with an Intel Core i9 processor, NVIDIA RTX A5000 graphics card, 128 GB DDR4 memory, a 1 TB SSD hard drive, and Windows 11 Pro 64 as the operating system. We first installed the Bibliometrix package and loaded it into R Studio . A .csv Excel file was uploaded to the Biblioshiny interface, as an Excel file is not the same as .csv Excel. The study also used Excel files (.csv) and portable network graphics files (.png) for the data analysis. The VOSviewer was used to present detailed information about RuV-based research, as well as for the extraction of other patterns.For the most productive and influential authors, various factors such as authorship pattern, degree of collaboration, and year-by-year groupings of articles were used in the analysis of their papers in PubMed. According to the analysis, between 2000 and 2021, 2500 documents that matched the study criteria were published in Dimensions .The primary information about studies on RuV on Dimensions from 2000 to 2021 is shown in The number of articles by Bradford\u2019s law zones in core sources was found to be 844 with 15,341 citations, and the number of core + zone 2 sources was 1675 with 29,473 citations, as shown in The articles were arranged in descending order by frequency of citation. The top three most cited papers were further analyzed for their citations. The top three locally cited documents were Banatvala, J. E., & Brown, D. W. (2004). Rubella. The Lancet, 363(9415), 1127\u20131137; Lambert, N., Strebel, P., Orenstein, W., Icenogle, J., & Poland, G. A. (2015). Rubella. The Lancet, 385(9984), 2297\u20132307; and Davidkin, I., Jokinen, S., Broman, M., Leinikki, P., & Peltola, H. (2008). Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up. The Journal of infectious diseases, 197(7), 950\u2013956, with 96, 92, and 91 local citations and 255, 214, and 247 global citations, respectively .The top three globally cited documents were Amanna, I. J., Carlson, N. E., & Slifka, M. K. (2007). Duration of humoral immunity to common viral and vaccine antigens. New England Journal of Medicine, 357(19), 1903\u20131915: Desailloud, R., & Hober, D. (2009). Viruses and thyroiditis: an update. Virology journal, 6(1), 1\u201314; Pollard, A. J., & Bijker, E. M. (2021). A guide to vaccinology: from basic principles to new developments. Nature Reviews Immunology, 21(2), 83\u2013100, with 874, 313, and 260 total citations and 54.62, 22.35, and 86.66 total citations per year.The top three locally cited references were Frey, T. K. (1994). Molecular biology of rubella virus. Advances in virus research, 44, 69\u2013160; McLean, H. Q., Fiebelkorn, A. P., Temte, J. L., & Wallace, G. S. (2013). Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports, 62(4), 1\u201334; and Miller, E., Cradock-Watson, J., & Pollock, T. (1982). Consequences of confirmed maternal rubella at successive stages of pregnancy. The Lancet, 320(8302), 781\u2013784, with 119, 103, and 101 citations, respectively.The top three authors who published the highest number of studies were Gregory A. Poland, Joseph Icenogle, and Inna G. Ovsyannikova, with 53, 44, and 42 articles and 11.06, 9.40, and 7.39 article fractions, respectively. The top three authors with the highest number of local citations were Inna G. Ovsyannikova, Stanley A. Plotkin, and Elizabeth Miller with 313, 270, and 234 citations, respectively. With respect to production over time, Gregory A. Poland, Joseph Icenogle, and Inna G. Ovsyannikova were the most prolific in 2000\u20132021.The three authors with the highest impact were Gregory A. Poland, Joseph Icenogle, and Inna G. Ovsyannikova, with an h-index of 26, 21, and 23; a g-index of 39, 35, and 34; m-index of 1.18, 0.95, and 1.211; total number of citations of 1655, 1280, and 1226; and publication year starting from 2001, 2001, and 2004, respectively. The above findings are shown in The majority of the studies included in the analysis were authored by researchers from the following three institutions : the CenMost of the studies were published by three countries: Japan (n = 303), Germany (n = 271), and the United Kingdom (n = 262). Despite the reality that East and South Asia and Africa bear a disproportionate share of the worldwide burden of rubella, their research output was limited. This should prompt health organizations to reconsider their support for and funding of RuV research in disease-endemic nations in order to create effective control and prevention strategies.The three outstanding countries whose publications on RuV received the highest number of citations were the United States , the United Kingdom (n = 3001), and Germany (n = 2332). The top three countries of corresponding authors of publications were the United States, Japan, and India, with 561, 149, and 123 articles; a frequency of 0.22, 0.06, and 0.06; 267, 75, and 68 inter-country publications; and 294, 74, and 55 intra-country publications, respectively .Vaccine from Elsevier, The Journal of Infectious Diseases (J. Infect. Dis.) from Oxford University Press, and Human Vaccines & Immunotherapeutics from Taylor & Francis, with 201, 78, and 67 articles, respectively.The top three relevant sources were the journals Vaccine from Elsevier, J. Infect. Dis., and The Lancet from Elsevier with 4841, 3131, and 2303 articles, respectively.The sources with the highest local citations (from reference lists) were Vaccine from Elsevier, J. Infect. Dis., and Human Vaccines & Immunotherapeutics from Taylor & Francis, with an h-index of 35, 30, and 11; a g-index of 51, 50, and 18; an m-index of 1.52, 1.50, and 0.91; total number of citations of 3977, 2746, and 467; and publication year starting from 2000, 2003, and 2011, respectively.The top three sources with respect to impact were J. Infect. Dis., BMC Infectious Diseases from Springer, and Vaccines from MDPI, with 76, 33, and 60 occurrences to date in comparison to the previous year\u2019s 76, 28, and 56 occurrences, respectively (The dynamics of the top three journals with respect to occurrences per year were: ectively .Overall, rubella, measles, and vaccination were the top three keywords used in the studies with 1417, 590, and 395 occurrences, respectively .This bibliometric analysis comprehensively described the research on rubella, a widespread disease in both industrialized and developing nations. Researchers worldwide have studied the detection, control, treatment, and avoidance of RuV. To our knowledge, no bibliometric analysis has been undertaken to date on the 2500 papers based on RuV research, despite the relevance of bibliometrics as a means of examining research volume, orientations, and collaborations between academics and medical practitioners. In recent decades, an increasing number of studies on the prevalence of RuV antibodies in various human groups have been published. In some 1.3 industrialized nations, RuV cases have surged by as much as 79% in recent years ,23. DiffThis study was undertaken for a citation analysis and its primary characteristics. In recent years, there has been a continuous increase in the number of RuV-related papers due to the global burden of this disease. Understanding the characteristics of published RuV research may be advantageous for multiple reasons. Our research revealed that the 2500 studies in Dimensions were referenced 31,897 times. The average number of citations per publication was 12.76, showing their significance and impact. Three studies were mentioned more than 1100 times in the scholarly literature. Previous research analyzing the RuV literature indicated a consistent growth in RuV-related publications over the past few decades. Using Web of Science, Deqiao Tian undertook a comprehensive literature review of pathogens, including health-threatening pathogens and biodefense-associated pathogens, and provided recommendations for future research on RuV . Japan, Vaccine; Human Vaccines & Immunotherapeutics; and The Journal of Infectious Diseases. Vaccine and Human Vaccines & Immunotherapeutics have published the highest number of articles on RuV. The Vaccine journal features a hybrid publication mode, meaning writers have the option of publication with subscription or open access, while Human Vaccines & Immunotherapeutics and The Journal of Infectious Diseases are open access with different waive options for authors from low-income countries, which greatly aids academics from developing nations to disseminate local material to a worldwide readership [Our study revealed that the highest number of corresponding authors of articles on RuV were from the United States, Japan, and India. This trajectory in publishing is inconsistent with the worldwide global distribution of the disease, as it is more prevalent in low- and middle-income nations, where it appears as both epidemics and sporadic infections. This study emphasized the need to establish research connections between experts from rich and resource-limited nations . To prevadership .This emphasizes the necessity of other journals adopting subscription or fee-waiver policies in order to attract high-quality publications from poorer nations . Local rThe data reported in this paper may be valuable for researchers and scientists in focusing their study aims on more relevant domains within the field of RuV research. In addition, it can assist academics and teachers by providing high-quality bibliographic references for educational purposes. Healthcare providers and parents need to be targeted with adequate information on RuV. Research on RuV should be encouraged, and health practitioners should be involved in collaborative research for public awareness. This study has several limitations, such as the fact that we only retrieved data from papers indexed in Dimensions; articles from other databases were not analyzed, which may have affected the conclusion. In addition, the quality of the most cited publications was not evaluated, which may have affected the interpretation of the results.This study discussed the most cited articles on RuV and their authors, institutions, and countries in the context of the RuV research output over the past two decades. In both developing and developed nations, RuV is regarded as the cause of one of the most contagious person-to-person airborne viral infections. Only two vaccines against RuV are available, MMR and MMRV, the latter containing weakened measles, mumps, rubella, and varicella viruses. The majority of studies on RuV are published by researchers from wealthy nations, and the United States was the most influential contributor. This study highlights the need to develop research partnerships between scholars from industrialized and low-income nations. To forestall and manage the spread of rubella, it is vital to motivate researchers, especially those from countries with few resources, to concentrate more on RuV research by providing them with technical and financial support. This study will also aid in formulating plans and policies for the prevention and control of RuV. The most dominant term used in these studies was vaccination against rubella virus, which highlights the significance of immunization, especially in infants. More importantly, it can guide decision-making strategies in medical services from a public health perspective."} +{"text": "Schizophrenia (SC) is considered the most serious of all mental disorders. Some antipsychotics are associated with weight gain and metabolic abnormalities. Whether SC itself causes obesity remains uncertain.We collected 185 first-episode drug-naive SC and 59 healthy controls (HCs) from the Third People\u2019s Hospital of Foshan, Guangdong, China, and distinguished their course of disease in order to understand the body mass index (BMI) and body fat metabolism of SC.B = 0.094, p < 0.001), duration , FBG , and TG were the risk factors for the increase of BMI. HDL was the protective factor.We found that excluding the drug factors, the longer the course of SC, the more obvious the increase of BMI and the higher the proportion of obesity. BMI was positively correlated with age, course of disease, fasting blood glucose (FBG), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and negatively correlated with high-density lipoprotein (HDL). The results of regression analysis were further proof that age (SC itself can increase BMI and easily lead to obesity. We should pay more attention to the monitoring of blood metabolism indicators, so as to reduce the risk of obesity and improve the quality of life of patients. Schizophrenia (SC) is considered the most serious of all mental disorders , 2. ManyDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) from August 2016 to September 2021 in the Department of Psychiatry, The Third People\u2019s Hospital of Foshan, Guangdong, People\u2019s Republic of China, were included. According to the course of disease, they were divided into groups A (duration < 6 months), B (6 months \u2264 duration<24 months), and C (duration \u2265 24 months).The outpatients and inpatients with SC, who met the diagnostic criteria of the Inclusion criteria were as follows: (1) SC: \u2780 18\u201345 years old ; \u2781 years of education \u2265 6; \u2782 Han nationality; \u2783 before test, did not take any antipsychotics, antidepressants, mood stabilizers, sedatives, etc.; (2) healthy control (HC): volunteers recruited through advertising in Foshan from March 2020 to December 2021; \u2780 18\u201345 years old; \u2781 no history or family history of psychosis; \u2782 Han nationality; \u2783 years of education \u2265 6; \u2784 gender, age, and education were matched with the patient group.Exclusion criteria were as follows: \u2460 comorbidity other mental disorders, including intellectual disability or other cognitive impairment; \u2461 patients with diabetes, hypertension, severe kidney, liver function damage, cardiac insufficiency, etc.; \u2462 those who did not cooperate with venous blood drawing due to phobia, etc.; \u2463 smoking habits (\u2265 1 cigarette per day) or drinking habits ; 1 unit alcohol = 480\u2013600 ml of beer = 350 ml of low alcohol liquor or red wine, yellow wine = 50 ml of high spirits (40\u00b0 or more).https://smitechasia.com). The positive and negative syndrome scale (PANSS) was used to assess the extent of the patient\u2019s mental symptoms.Details such as names, gender, and age were collected through the interviews from subjects who were willing to participate, after receiving the signed informed consent form. Then, the weight, height, and BMI of these subjects were measured with Automatic Measuring Stadiometer BSM370 , A (n = 92), B (n = 45), and C (n = 48), while 10 subjects were excluded due to consumption of breakfast before drawing blood or due to not showing interest in performing blood test.There were 244 participants in this study, including HC (p > 0.05). Also, there were significant differences in BMI and FBG (p < 0.05). The incidence of obesity in groups HG, A, B, and C was 5.26, 7.61, 15.56, and 22.92%, respectively, and the incidence of overweight was 22.81, 27.17, 22.22, and 31.25%, respectively , PANSS (N), and PANSS (G) were not correlated with BMI .F = 16.394, p < 0.001) was established. Finally, the elements such as age, duration, FBG, HDL, and TG, were considered for the model (Taking BMI as the dependent variable (Y) and age, duration, HDL, LDL, TG, and TC as independent variables (X), and gender as a covariate, a stepwise multiple linear regression model (he model .Our study included first-episode, drug-naive SC with a different course of disease. By comparing their blood metabolic indexes, we found that after excluding the drug factors, the longer is the course of SC, the more obvious is the increase of BMI, and the higher is the proportion of obesity.A previous study has shown that there was no significant difference in the incidence of obesity in first-episode SC compared with HC . HoweverComparing the FBG of each group, we found that the FBG decreased in patients with 0\u20136 months course. As we know that SC always starts with negative or positive symptoms , psychotTo further explore the factors affecting BMI, we correlated the metabolic indexes and PANSS scores with BMI. The results showed that BMI was positively correlated with age, course of disease, FBG, LDL, TG, and TC, negatively correlated with HDL, and had no correlation with the scores of PANSS in each group, which meant that the severity of SC had nothing to do with BMI. The incidence of obesity in SC increased with age, similar to most mental disorders , 20. At Of course, it is best that we conduct a longitudinal follow-up study on the first-episode, drug-naive SC, and do not use any drugs to intervene, which obviously violates ethics and humanitarianism. So, we had to test this hypothesis by selecting untreated SC patients with a different course of disease. In addition, patients with a long course of disease tend to shrink back, including diet and living habits, which would lead to the deviation of our study. Overall, SC itself can increase BMI and easily lead to obesity. We should pay more attention to monitoring of blood metabolism indicators, so as to reduce the risk of obesity and improve the quality of life of patients.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of the Third People\u2019s Hospital of Foshan, China. The patients/participants provided their written informed consent to participate in this study.JL, YC, and YY made great contributions to the conception, design, and writing of the article. XX, XL, ZL, CX, and GX provided assistance in the acquisition, analysis, and interpretation of data. All authors approved the publication of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cW.M. Keck Science Department, Scripps and Pitzer Colleges, Claremont, CA, United States,\u201d it should be \u201cW.M. Keck Science Department, Claremont McKenna, Scripps and Pitzer Colleges, Claremont, CA, United States\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Pages 11611 and 11612, references 18 and 42 should be switched,such that ref 18, cited on page 11598, refers to the work by Sorrentiet al., and ref 42, cited on page 11599, refers to the work by Amataet al.Page 11599. A new reference (cited here as ref ("} +{"text": "Materials, which has the goal of publishing original research and review articles focused on carbon nanotubes, graphene, activated carbon, graphite, pencil graphite, graphene oxide, graphene nanoplatelets, pyrolytic graphite, organic mass derived carbon, fullerenes, diamond, glassy carbon, carbon fibers, and other composites for electrode preparation and its applications.Carbon-Based Composite Materials for Electrodes is a new open Special Issue of In the last decade, carbon composites have been playing a significant role in the field of multidisciplinary science and technology. Because the carbon composites are green and economical with brilliant chemical, mechanical, electronic, and surface properties, carbon composite electrodes find many applications in sensing systems, energy storage and management, fuel cell construction, batteries preparation, molecular and ion recognition, electro-synthesis, drug delivery, and more ,2.Carbon-Based Composite Materials for Electrodes\u201d.All the possible carbon composites and their applications are welcomed in the current Special Issue entitled \u201c"} +{"text": "Hemileia vastatrix and Hypothenemus hampei. Despite technological support, these pests have caused 20% to 40% production losses, a 50% to 60% deficit in performance, and a cost of between USD 70 million and USD 220 million to the world economies, which forces us to rethink actions centered on people as the key elements to develop appropriate solutions. For this, the present study presents a technological proposal centered on small indigenous coffee producer requirements for introducing Industry 5.0 technologies, considering roadmapping, knowledge management, statistical analysis, and the social, productive, and digital contexts of five localities in Mexico. The results show a correlation between monitoring and control, soil analysis, the creation of organic fertilizers, accompaniment, and coffee experimentation, as the actions to be implemented, proposing the introduction of a mobile application; sensors, virtual platforms, dome-shaped greenhouses, and spectrophotometric technology as relevant technologies centered on indigenous coffee producers\u2019 requirements. This study is important for policymakers, academics, and producers who wish to develop strategies centered on people in Mexico and the world.The coffee plant, with more than 40 billion shrubs, 9 million tons of grains produced, and 80% of its production accounted for by small-scale producers, has been severely damaged since the emergence of Historically, plants have played an essential role in the evolution of human beings. Due to their role in the production of oxygen, humidity regulation, the stability of the climate and soil, fuel, food, and medicine for protecting the coronary arterial wall and against oxidative inflammatory disease ,2,3, plaWorldwide, around 300,000 edible plants exist, of which approximately 6000 are cultivated by humans, using about 200 to produce food ,6. AmongCoffea arabica) and canephora (Coffea canephora) as its two most important varieties, is a tropical tree with green leaves and flowers that give an oval fruit called a coffee bean. Its development requires best management practices, temperatures between 15 and 30 degrees Celsius, pluvial precipitations of 1500 to 3000 mm for a proper development, and 9 to 11 months from flowering, on average, to produce a ripe cherry . The retions of .For the social variables, the results show a positive correlation with gender (0.028) and a negative correlation with age (\u22120.009), time producing (\u22120.013), and family members (\u22120.063). The productive variables present a positive correlation with the production level (0.001), varieties (0.250), coffee tree age (0.162), pruning (0.312), pruning frequency (0.305), fertilizer (0.320), type of soil compost (0.121), additional crops (0.151), and pest incidence (0.041). However, negative results were found for the cultivated area (\u22120.112), flora (\u22120.058), and soil compost (\u22120.037) see .The production level and pest incidence can be controlled by monitoring coffee leaf rust. For this, the development and involvement of producers through a mobile application for early detection of the disease is registered as a feasible option, promoting data management and processing to boost the learning process . This caThe positive statistical correlations between the social and productive variables and actions to be implemented, such as monitoring and control of coffee leaf rust, accompaniment during the growth of the coffee plant, soil analysis, the creation of organic fertilizers, and experimentation with the environment, provide the guideline to make the following technological proposal: This technology has been implemented in Guatemala and Nicaragua. In Guatemala, it has mainly been implemented in southern regions I, II, III, and IV , locatedIn parallel, the introduction of this technology can be for accompaniment during the growth of the coffee plant. To influence the management of the level of production, proper management of the varieties at different ages, pruning development, and the reduction in the rust incidence should be implemented based on the existing correlation between the strategies and the production context. This proposal aligns with by recom2.The type of soil compost is related to soil analysis. For this, sensors and computer tomography ,105 can This technological strategy has been used in Colombia through sensors to measure the soil moisture and indicate variations . At the In Colombia, coffee departments such as Magdalena, Cesar, and Cuca have multidimensional poverty of 19.6% to 33.4% . MagdaleThis type of technology, related to soil analysis, could be developed from the knowledge and experiences of local institutions in order to be introduced into the coffee context as a soil laboratory (see ).3.In relation to fertilizers/pesticides, the creation of organic fertilizers has a direct relationship. An option can be to reuse coffee pulp as a good source of compost. For this, a dome-shaped greenhouse to take advantage of solar radiation can be a simple technology since it does not require intervention for its management; it just needs the care of depositing and rotating the coffee pulp continuously to collect the black liquid that contains all the nutrients that it exudes after some time ,117, whiA similar technological initiative has already been experienced in Vilcabamba, Ecuador, allowing comparisons of the efficiency and time of grain drying . Vilcaba4.Regarding varieties and their experimentation with the environment, due to the existence of coffee plants without rust, evaluation of the presence of phenolic compounds and proteins, following , is suggSpectrophotometric and sensor technologies have already been considered in forage studies for cattle production systems in Veracruz, Mexico . TherefoThe number of indigenous people in the coffee-producing localities of El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista in Oaxaca, Mexico, is proportionally similar to the 949 producers from 35 communities in Chiapas, recorded by . The altRegarding the academic level, the results obtained are a slightly lower than those reported by , establiThe access to computers (0% to 8.7%), cell phones (32.2% to 65.9%), and internet (1.05% to 59.09%) of indigenous communities from El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista is similar to that reported in the same populations in Central and South American countries. For example, there is 2% computer access in Nicaragua and Colombia, 3% in Venezuela, 5% in Panama, and 8% in Ecuador, while there is 39% cell phone access in Chile, 48% in El Salvador, 53% in Panama, 54% in Ecuador, and 64% in Costa Rica, in similar communities. Regarding the internet, the situation is similar in Venezuela with 1% and Bolivia with 4%, while the condition is slightly better by 7% than Panama (highest), with 52% . The extThe gender of coffee producers from El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista is similar to that found in , which rRegarding the coffee production level, the number of kilograms produced by inhabitants in the localities of El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista was 404 kg less than that produced by their counterparts from Guerrero, Mexico, with 689 kg . The cofIn relation to fertilizers/pesticides used against coffee leaf rust, the use of oxicloruro and organic products is in line with ,140, finThe coffee production process in the localities of El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista is similar to that reported by , in relaThe expectations and current situation expressed by indigenous coffee producers from El Pajarito, Llano Coyul, Ocotal, Guadalupe, and Buenavista are in line with those expressed by indigenous coffee producers from Guerrero, Mexico, in the sense of effective actions against coffee pests and diseases, due to the presence of coffee leaf rust and coffee berry borers. There are differences in the actions to be implemented; while the results of this study show the action of monitoring, their counterparts in Guerrero, Mexico, focused on knowledge and technology management networks, in addition to greenhouses .The positive statistical correlations of the socio-productive context, specifically of age, production level, and additional crops, with actions to be implemented align with the results in Chiapper se, an accompaniment in the development of the coffee plant. The implementation of soil analysis through sensors and computers is in line with the proposal developed by is requ"} +{"text": "In \u201cRacial Bias Beliefs Related to COVID-19 Among Asian Americans, Native Hawaiians, and Pacific Islanders: Findings From the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS)\u201d :e38443), two errors were noted.In the originally published article, author Linda G Park was inadvertently left out of the authorship, and the order of authors was listed as follows:Van Ta Park, Janice Y Tsoh, Marcelle Dougan, Bora Nam, Marian Tzuang, Quyen N Vuong, Joon Bang, Oanh L Meyer.In the corrected article, author Linda G Park is listed as the sixth author, and the order of authors has been updated as follows:Van Ta Park, Janice Y Tsoh, Marcelle Dougan, Bora Nam, Marian Tzuang, Linda G Park, Quyen N Vuong, Joon Bang, Oanh L Meyer.In the originally published article, the phone number of the Corresponding Author was incorrect. The phone number has been corrected to:1 415 514 3318The correction will appear in the online version of the paper on the JMIR Publications website on October 31, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "In \u201cEffect of Door-to-Door Screening and Awareness Generation Activities in the Catchment Areas of Vision Centers on Service Use: Protocol for a Randomized Experimental Study\u201d :e31951) one error was noted.The following text was originally published in the Acknowledgments section of the paper. This text has now been moved instead to the Authors\u2019 Contributions section:The Operational Research Capacity Building Group consists of the following authors, who contributed equally to the paper: Gudlavalleti VS Murthy, Rajan Shukla, Samiksha Singh, Shailaja Tetali, Suresh K Rathi, Hemant Mahajan, Melissa G Lewis, Hira Pant, Tripura Batchu, Anirudh G Gaurang, Suzanne Gilbert, Ken Bassett, Priya A Reddy, Parami Dhakhwa, Ram P Kandel, Kuldeep Singh, and Prasanna Sharma.Accordingly, the affiliation for the group author Operational Research Capacity Building Group has been changed from:See Acknowledgmentsto:See Authors\u2019 ContributionsThe corrections will appear in the online version of the paper on the JMIR Publications website on January 18, 2022, with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "The Authors wish to make the following corrections to their article .Affiliations 2 and 3 have been corrected to:2School of Medicine, University of Queensland, Herston, QLD, 4006, Australia3Epigenetics and Diseases Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, AustraliaJason S. Lee wishes to add another affiliation:7School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, AustraliaThe Publisher omitted the following joint authorship statement:\u2021The authors wish it to be known that, in their opinion, the last two authors should be regarded as Joint Last AuthorsThe published article has been updated to reflect these corrections."} +{"text": "Background: Global mobility is increasingly associated with the emergence of \u201cunusual\u201d infectious agents. At the beginning of 2019, a putative outbreak of Impetigo contagiosa occurred in a kindergarten in Regensburg, Germany, that was mainly attended by children with a migrant background. After thorough examination, the outbreak was classified as infection with Trichophyton (T.) violaceum.Methods: Based on case investigations, infection control measures, disinfection, and cleaning were implemented. Microscopy of native specimens, fungal cultures, and polymerase chain reaction were used for diagnosis. Additionally, a systematic literature search in Medline, followed by a quantitative analysis of epidemiological data from Europe, were performed.Results: Between January and November 2019, 12 cases of tinea were diagnosed in 7 educators and 2 household members. Children were initially not affected. T. violaceum was only detected in 2 patients. No extensive screening measures were carried out after risk-benefit assessment. Studies on T. violaceum in Europe are heterogeneous, and the number of cases and the prevalence vary considerably. The pathogen is mainly found in children of African descent who clinically present with tinea capitis.Discussion: In the present case, the source of infection and the chain of transmission remained unclear. The pathogen could only be diagnosed in 2 cases. In Europe, the (re)emergence of pathogens such as T. violaceum is likely to be caused by increasing migration and travel. Pathogens should be identified for epidemiological reasons in all cases. In outbreaks, measures must be adapted to the dynamics of the individual outbreak after assessment of the risks, benefits, and proportionality. Trichophyton (T.) violaceum is a pathogen of the Trichophyton rubrum complex, which is rather rare in Europe, but currently endemic mainly in Africa and Asia. T. violaceum usually causes tinea capitis in children from endemic areas. T. violaceum spreads along the hair follicles within the hair shafts (endothrix infection) and may cause scaling plaques on the skin. These plaques are often associated with minimal inflammatory reactions but may be protracted and become chronic. Dermatophytes grow slowly at temperatures under 30\u00b0C and do not result in systemic fungal infection , , , , , , , , , , , , . B. BT. vioT. capitis , , , , , , , , , , , . HoweverT. violaceum from Europe report a different prevalence of T. violaceum, depending on the assessed population or the number of samples examined. Most studies were conducted in southern or southeastern European countries. A higher prevalence of T. violaceum is seen in people of African descent , , , , , , , , , , , , , , , , , , , a, aT. vioT. violaceum in Europe are heterogeneous, scarce and limited by selection bias.Global mobility is associated with the (re)occurrence of \u201cunusual\u201d infectious agents. PCR diagnostics will increasingly become relevant for mycotic diseases in the near future. In case of dermatophytic outbreaks, extensive screening and treatment of asymptomatic carriers must be considered after risk-benefit assessment, depending on the dynamics of the individual outbreak. Data on the epidemiology of The authors declare that there is no conflict of interest.No funding was received. We thank Professor Pietro Nenoff for conducting the specific PCR diagnostics and Monika Sch\u00f6ll for the linguistic revision of the manuscript."} +{"text": "Rhacocarpus purpurascens (Brid.) Paris, Sphagnum sp. and Thuidium delicatulum (Hedw.) Schimp.) from Ecuador. Significant differences were found for the three species in the concentrations of Al, Mn, Fe and Zn between urban and control areas, pointing to the Central zone as the main source of contamination with the highest concentrations of Al, Fe, Mn and Zn, related to vehicular traffic. Lead did not differ between zones for Rhacocarpus purpurascens and Sphagnum sp.; however, Thuidium delicatulum accumulated different concentrations between urban areas and the control areas. The three species of mosses provided valuable information on the contamination of Al, Fe, Mn, Pb and Zn in the urban area of the city of Loja, and therefore can be used in future air quality monitoring programs over time in tropical cities.Air pollution is one of the main global environmental problems, where bryophytes, due to their high capacity to retain metals and other pollutants, have been widely used in active air quality monitoring studies in temperate and tropical zones. Thus, in this study, we analyzed for the first time the concentrations of eight metals in three species of transplanted mosses ( Anthropogenic activities such as industrial discharges, agricultural practices, combustion, vehicular traffic, and poor waste management are the main causes of environmental pollution in urban areas ,2, causiVehicular traffic is one of the most important sources of air pollution in urban areas includinIn this context, one of the methods to assess air quality is biomonitoring based on the use of biological species to detect air pollutants, allowing the establishment of an environmental quality control program, including air . BiomoniCeratodon purpureus (Hedw.) Brid. [Haplocladium microphyllum (Hedw.) Broth. [Hylocomium splendens (Hedw.) Schimp. [Hypnum cupressiforme Hedw. [Pleurozium schreberi (Brid.) Mitt. [Scleropodium purum (Hedw.) Limpr. [Sphagnum denticulatum Brid. [Sphagnum girgensohnii Russow. [Thuidium delicatulum (Hedw.) Schimp. [Thuidium tamariscellum Bosch and Sande Lac. [Bryophytes take up essential elements directly from the air and have stronger adsorption capacities for metals ,19,20; t.) Brid. , Haplocl) Broth. , Hylocom Schimp. ,26, Hypnme Hedw. ,27, Pleu.) Mitt. , Sclerop) Limpr. , Sphagnuum Brid. , Sphagnu Russow. , Thuidiu Schimp. , and Thunde Lac. have beende Lac. , the coande Lac. ,34. HoweRhacocarpus purpurascens, Sphagnum sp. and Thuidium delicatulum) due to the fact that urban areas of the city of Loja, Ecuador have high levels of air pollution related to vehicular traffic [In Ecuador, only one active biomonitoring study has been conducted using mosses as indicators of air pollution in the city of Quito , where t traffic ,37. We hThe study was carried out in the city of Loja, located in the south of Ecuador at 2100 m a.s.l. For monitoring purposes, the city of Loja was divided into three zones , with three locations in the North and South zones and four locations in the Central zone . The des\u22121, 21.27 mg g\u22121, 53.49 mg g\u22121, 39.48 mg g\u22121, and 91.37 mg g\u22121, respectively. The Central zone (C) is characterized by a high level of air pollution with metals and a high degree of urbanization. In this area, levels of Cd, Cu, Mn, Pb and Zn in the air reach values up to 34.66 mg g\u22121, 25.41 mg g\u22121, 20.03 mg g\u22121, 25.29 mg g\u22121, and 100.54 mg g\u22121, respectively. Finally, the North zone (N) is an urban area with high levels of metals, but the zone still has some recreational parks. In this area, levels of Cd, Cu, Mn, Pb and Zn in the air reach values up to 27.99 mg g\u22121, 31.02 mg g\u22121, 56.81 mg g\u22121, 42.95 mg g\u22121, and 44.46 mg g\u22121, respectively [The South zone (S) is characterized by a greater concentration of metals in the air and by recent urban development. Here, Cd, Cu, Mn, Pb and Zn in the air reach values up to 30.83 mg gRhacocarpus purpurascens, Sphagnum sp. and Thuidium delicatulum. Samples were collected from an uncontaminated area in the buffer zone (Control zone: Ctr) of the Podocarpus National Park, which is located on the outskirts of the city . The moss vouchers were deposited in Herbario de la Universidad T\u00e9cnica Particular de Loja (HUTPL).Transplants were carried out using terrestrial mosses of the species Rhacocarpus purpurascens 6 by CEM Corporation was used . The digp-value > 0.05) and the nonparametric Kruskal\u2013Wallis test for those that did not have a normal distribution . In addition, to identify significant differences in metal accumulation between zones, the Tukey HSD post hoc multiple comparison test was implemented as a parametric test, and Dunn\u2019s non-parametric test with the Dunn test package was used [To evaluate the changes in the concentration of metals in each of the zones, parametric and nonparametric statistical tests were performed based on the Shapiro\u2013Wilk normality test. Cadmium (Cd), copper (Cu) and nickel (Ni) showed values of zero for the control samples and the samples transplanted in the city; thus, these metals were not considered in the statistical analyses. For the three species, a one-way analysis of variance was performed (ANOVA) for metals that met normality assumptions for Fe and Mn , manganese (Mn), iron (Fe) and zinc (Zn) between the urbanized areas and the control samples. Lead (Pb) concentrations did not show significant differences for the control samples for nificant . On the e and Mn .Sphagnum sp., the Tukey HSD test and the Dunn test showed significant differences between the accumulation of metals in the control samples and the urban zones for Al, Fe, Mn and Zn , manganese (Mn), iron (Fe) and zinc (Zn) between the urban areas and the control samples. Similar to our results, previous studies have shown that the highest concentrations of these elements were observed in areas characterized by the intense flow of public transportation ,31,47,55Rhacocarpus purpurascens and Sphagnum sp., due to the fact that industrial areas report higher Pb concentration levels than areas with high vehicular traffic [In addition, corroborating this pattern, passive monitoring studies using lichens and bromeliads in the city of Loja have identified urban areas with high levels of contaminants such as zinc and manganese ,37. All traffic \u2014as in ouRhacocarpus purpurascens, significant differences were shown between the accumulation of metals in the control samples and urban areas only for two of the metals analyzed . This suggests that the species has a low capacity to retain certain metals; this may be due to the structure of the cell walls of the leaves, which are highly porous and thus water can easily penetrate the reticular layer, increasing the likelihood that certain metals are leached [Sphagnum sp., significant differences were found for Al, Fe, Mn and Zn between the control samples and the urban areas . Sphagnum sp. has a high capacity to retain metals related to vehicular traffic, as shown by previous studies that have observed positive results in terms of the accumulation of Al, Fe, Mn, Pb and Zn in urban areas [For leached ,63. In San areas ,61,64,65an areas ,67,68.Thuidium delicatulum Al, Fe, Mn, Pb and Zn showed significant differences between control samples and the urban areas. These results are in agreement with Rodr\u00edguez-Quiel et al. [T. delicatulum and Pseudoscleropodium purumis is effective for determining the variation of Al, Fe, Pb and Zn as the main air pollutants. Likewise, our results show that of the three mosses used in the study, T. delicatulum showed significant differences for lead, which indicates that the physiology and morphology of mosses are involved in the process of bioconcentration and absorption of pollutants [On the other hand, for l et al. and Castl et al. , who shollutants ,70.Rhacocarpus purpurascens, Sphagnum sp., and Thuidium delicatulum) related to vehicular traffic. Sphagnum sp. and T. delicatulum point to the Central zone as the main source of contamination, with the highest concentrations of Al, Fe, Mn and Zn. Thus, this study might serve as a reference for future investigations on the bioaccumulation of pollutants in Rhacocarpus purpurascens, Sphagnum sp., and Thuidium delicatulum in similar urban tropical areas.The three urban zones of the city of Loja showed higher concentrations of Al, Fe, Mn and Zn compared to the control samples for the three species of mosses ("} +{"text": "Author Contributions Statement appears below.\u201cMohamad Nageeb Hassan\u201d was not included as an author in the published article. The corrected \u201cSSh and KM conceived and designed the study. SSh performed the experiments, data collection, data analysis and drafted the manuscript. CK, SM-A, MY, HD, DE, ST, and MH assisted with data collection, data analysis/interpretation and drafting the manuscript. AS, AB, SSu, and KM assisted with data analysis/interpretation and drafting the manuscript. All authors read and approved the final version of the manuscript.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following the publication of the original article [1], it was brought to our attention that the first author is affiliated with the below two institutions:1. Department of Endocrinology, Genetics and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing 100,045, China.2. Department of Endocrinology, Shenzhen Children\u2019s Hospital, Shenzhen 518,038, China.This is shown in the \"Author details\" section of this Correction as well as the original article which has now been revised."} +{"text": "Currently, the knowledge of associations among newly recovered cases (NR), newly healed cases (NH), newly confirmed cases (NC), and newly dead cases (ND) can help to monitor, evaluate, predict, control, and curb the spreading of coronavirus disease 2019 (COVID-19). This study aimed to explore the panel associations of ND, NH, and NR with NC.Data from China Data Lab in Harvard Dataverse with China , the United States of America , and the World had been analyzed. The main variables included in the present analysis were ND, NH, NR, and NC. Pooled regression, stacked within-transformed linear regression, quantile regression for panel data, random-effects negative binomial regression, and random-effects Poisson regression were conducted to reflect the associations of ND, NH, and NR with NC. Event study analyses were performed to explore how the key events influenced NC.Descriptive analyses showed that mean value of ND/NC ratio regarding China was more than those regarding the USA and the World. The results from tentative analysis reported the significant relationships among ND, NH, NR, and NC regarding China, the USA, and the World. Panel regressions confirmed associations of ND, NH, and NR with NC regarding China, the USA, and the World. Panel event study showed that key events influenced NC regarding USA and the World more greatly than that regarding China.The findings in this study confirmed the panel associations of ND, NH, and NR with NC in the three datasets. The efficiencies of various control strategies of COVID-19 pandemic across the globe were compared by the regression outcomes. Future direction of research work could explore the influencing mechanisms of the panel associations. Despite travel restrictions and limiTill now, regarding the epidemic evolution of total COVID-19 infections, analytical methods of control efficiency of COVID-19 pandemic are limited and biased. Notably, trend forecast with publicly available micro epidemiological data has been particularly the mainstream in the field of COVID-19 control. For example, multiple studies forecast a trend of the COVID-19 spreading in China . MoreoveTo date, analytical tools in published studies were limited to reflect the associations of ND, NH, and NR with NC. For example, a substantial body of time series models and simulations employed not spatial and locational factors but temporal factors \u201326. SeveFurthermore, policy interventions were not considered in the current studies. From December 12, 2019 till now, a series of daily policies and regulations were released by the Chinese government, global organizations, and western countries and documented in China Data Lab . With puThe progress in COVID-19 crisis was formally characterized by ND, NH, NR, and NC. Thus, this study based on publicly available longitudinal datasets to explore panel associations of ND, NH, and NR with NC. According to the presumptions of the panel models, pooled regression, stacked within-transformed linear regression, quantile regression for panel data, random-effects negative binomial regression, and random-effects Poisson regression would be conducted to reflect the associations of interest regarding China, the USA, and the World. Subsequently, panel event study was performed to reflect the trends of NC. Consequently, the endemic control performance would be further analyzed, assessed, and compared on the basis of the empirical outcomes.Daily cases in China included the numbers of NH, NC, and ND at the province-level unit available from January 15, 2020 to January 14, 2021 . Daily cBefore designing statistical strategies, the relationships between NC and ND, between NH and NC, and between NH and ND regarding China, the relationship between ND and NC regarding USA, and the relationships between NC and ND, between NC and NR, and between ND and NR regarding the World were depicted by front-and-back plots in Figs. Tentative analysis on the relationships between ND, NH, NR, and NC was performed by a one-stop solution for robust inference with multiway clustering (Stata package vcemway) . In the The main associations of interest in this study were panel associations of ND and NH with NC regarding China, panel associations between ND and NC regarding the USA, and panel associations of ND and NR with NC regarding the World. In the pooled regression analysis, the regions of China , the USA , and the World were also considered as covariates.The count data of ND, NH, NR, and NC tended to follow the Poisson or negative binomial distributions. In this large sample, the distributions approached to normal distributions approximately. Regarding the associations, the feasible panel models could be linear and nonlinear models. When NR, NH, NC, and ND were considered as count data, random-effects negative binomial regression and random-effects Poisson regression could be employed to reflect the associations of interest in nonlinear models. When ND, NH, NR, and NC were considered as continuous variables, pooled regression, stacked within-transformed linear regression, and quantile regression for panel data could be employed to explore the associations of interest in linear models.Regarding China, the panel associations of ND and NH with NC could be found by using the regression model :1\\documeRegarding the USA, the panel associations between ND and NC could be found by using the regression model :2\\documeRegarding the World, the panel associations of ND and NR with NC could be found by using the regression model :3\\docume\u03b20 was constant. \u03b21 and \u03b22 were coefficients. \u03bc1, \u03bc2, and \u03bc3 were random errors. If optimized iterations were not concave, the possible calculations of chosen methods were deleted.Here, Regarding cubic or quadratic equations, this study aimed to explore the associations of interest rather than dynamic system analysis. Thus, it was unnecessary to conduct regressions with squared terms or interactions.Pooled regressions are usually carried out to analyze available time series of cross-sections. The main advantage of pooled regression is the ability to measure different factors at the region level and aggregate results at the national level. The main disadvantages of pooled regression are overestimating and underestimating the impact in the regions.Stacked within-transformed linear regression analysis was performed by Stata program xtstackreg . RegardiT [Quantile regression for panel data was performed by Stata program qregpd with Nelder\u2013Mead optimization . LikewisT . Simultahttp://en.nhc.gov.cn/2020-02/06/c_76511.htm). Coronavirus Guidelines for America was issued on March 16, 2020 in the USA (https://www.whitehouse.gov/briefings-statements/coronavirus-guidelines-america/). On March 11, 2020, WHO characterized COVID-19 as a pandemic (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen).This study included panel models for the associations of interest and prediction models for the effects of key events. A panel event study implemented by the program \u201ceventdd\u201d in Stata was emplAll analyses were performed with Stata .Table In Table p\u2009<\u20090.001), ND , Central China , East China , Northeast China , and Western China had significantly positive associations with NC.In Table p\u2009<\u20090.001) and the West Region had significantly positive associations with NC, while Mid-Atlantic Region had significantly negative association with NC.In the USA, ND , ND , Africa , and Europe had significantly positive associations with NC.Regarding the World, NR were treated as missing values. The results from the estimation presented in Table The results from the estimation presented in Table The results from the estimation presented in Table Figure\u00a0R squares regarding China Total, Central China, East China, Northeast China, and Western China were 0.9841, 0.9864, 0.9933, 0.9917, and 0.9895, respectively. R squares regarding the USA Total, Mid-West Region, Mid-Atlantic Region, New England, the South Region, the Southwest Region, and the West Region were 0.8056, 0.9259, 0.8886, 0.9131, 0.9654, 0.9899, and 0.9739, respectively. R squares regarding the World Total, Africa, Asia, Europe, North America, Oceania, and South America were 0.9488, 0.9984, 0.9934, 0.8921, 0.9958, 0.9861, and 0.9992, respectively.Exponential rise of NC was plotted in the Figs. This study employed publicly available daily datasets including the samples of China, the USA, and the World and obtained the associations of ND, NR, and NH with NC regarding China, the USA, and the World, respectively. In panel event study, curve lines showed key events influenced NC regarding the USA and the World significantly, while straight line showed key events nearly had no significant influence on NC regarding China.Congruent with a prior study , this stWith regard to methodologies, the findings in panel event study were in line with prior studies. For example, an exploratory data analysis with visualizations had been made to understand the number of NR, NC, and ND in China . An 82-dChanges of COVID-19 ND, NH, NR, and NC in various regions could be influenced by life style, environmental factors, regulations, and progressing stages. Regarding life style, change in social distancing , increasThere were small curves in the point estimation regarding China and wide range of trajectories regarding the USA. This could be partially explained by several studies. For example, a study showed rapid nucleation and diffusion in January 2020 followed by rapid NC decrease in February in China, while the USA showed a wide range of trajectories, with an abrupt transition from slow NC increase in January and February, to rapid geographic dispersion shortly before mobility reductions occurred in March . RegardiRegarding data sources, this study employed three datasets. The current study had a large sample size which increased the precision of the study. Additionally, more than 1-year period could provide reliable results regarding epidemic control and daily changes in the prevalence of COVID-19 conditions. Regarding statistical methods, this study adopted several advanced panel regression methods. Especially, the event study with difference in difference was used to analyze the role of key events. Compared with the other studies \u201369, the There were several limitations. First, several variables including demographics, financial support, and international aids were not taken into account. Statistically, a study in South Korea found that sex, region, and infection reasons affected on both NR and ND . Second,Using panel analysis and data collected in China province-level units, the USA state-level units, and the World country-level units , regressions confirmed the positive panel associations between NH, ND, and NC regarding China, between ND and NC regarding the USA, between NR, ND, and NC regarding the World. Panel event study showed key events influenced NC regarding the World and the USA more forceful and unsteady as compared to that regarding China. Future work on the basis of the current study should be performed on the influencing mechanism of the panel associations."} +{"text": "Hedychium gardnerianum Sheph. ex Ker Gawl. is one of the 100 world's worst invasive alien species and the research target in areas as diverse as biological control, natural fibres uses, taxonomy or the biological activity of its compounds. This review aimed to clarify the taxonomic status and the native range of H. gardnerianum and bring accuracy to the history of its introduction and escape from cultivation through the analysis of the increasing number of accessible digitalized dry specimens and grey literature. The analysis of the available information allowed to conclude that: (a) Hedychium gardnerianum is a validly published name, the authority of the name is Sheph. ex Ker Gawl., the species holotype is the illustration published along with the species name, and the Natural History Museum BM000574691 specimen collected in 1815 is the first dried specimen of H. gardnerianum; (b) This species is native to the Central and Eastern Nepal, Bhutan, Northeast India and North Myanmar; (c) The species was cultivated at Cambridge Botanical Garden since 1818 and the first known herbarium specimen collected in Europe dates back to 1821; (d) Kathmandu and Khasi Hills (India) specimens are considered two varieties of the same species and the BM000574691 specimen is the lectotype of H. gardnerianum var. speciosum; (e) Specimens, references, and/or pictures support that H. gardnerianum escaped from cultivation at Galicia (Spain), Azores archipelago, Madeira, Tenerife, Cuba, Jamaica, Martinique, Trinidad, Ascension, Mexico, Honduras, Brazil, South Africa, Swaziland, Zimbabwe, R\u00e9union, Mauritius, Australia, New Zealand, Fiji, Hawaii, and Vietnam; and (f) H. gardnerianum is a serious pest in Azores, Madeira, Jamaica, R\u00e9union, New Zealand and Hawaii and continues to expand its distribution area in South and Central America, Australia and Southern Africa. This review presents linear raw information compiled with precision, allowing the world databases updating their data but also gives the most detailed information possible to each country/region identifying new regions of concern and updating the invasiveness status in each region. Hedychium gardnerianum Sheph. ex Ker Gawl. Hedychiumwl. IPNI with higH. gardnerianum control actions with the specimen collected by Matthew Robert Smith and referred by Wallich in 1820 and his team, will have collected an 0 Roscoe . The pro0 Roscoe . In 1824H. speciosum was not validly published in 1820 since no illustration or dried specimen is clearly identified: 'My examination of this stately plant has hitherto been confined to a well-preserved spike and a few leaves only, which however point it out as the largest of the genus\u2019 and H. gardnerianum var. speciosum Horan. from the Khasi Hills (India) Fig.\u00a0. At the H. gardnerianum is native to the Central and Eastern Nepal and the Khasia Hills (India) allowed to update the world distribution and status of um Table .Table 5HH. gardnerianum is only considered invasive at R\u00e9union (Soubeyran H. gardnerianum is mentioned as cultivated at Saint-Claude in 1897 (the Atlantic Guadeloupe Island) , the species is not mentioned in the book \u2018Garden Plants of Japan\u2019 (CABI um) CABI Table 5um) CABI k, Dominium) CABI , Guadeloum) CABI , Kenya (um) CABI , Tasmanium) CABI , New Calum) CABI , Cook Isum) CABI , French um) CABI , Federatum) CABI , and Chium CABI kH. gardnerianum had or is escaped from cultivation at Galicia (Spain), Azores archipelago, Madeira Island, Tenerife Island, Cuba, Jamaica, Martinique, Trinidad, Ascension, Mexico, Honduras, Brazil, South Africa, Swaziland, Zimbabwe, R\u00e9union, Mauritius, Australia New Zealand, Fiji, Hawaii, and Vietnam . Although no recent botanic studies were made to prove the spreading of this species, the species is mentioned in 3 environmental impact assessments at Mapastepec (Chiapas) and the nearby states of Oaxaca and Campeche a 2006 Master thesis with no reference of the putative source of this escape , found at Ponta Delgada Public Library and Regional Archive. Other nineteenth century documents available online allowed to verify the presence of this species as an ornamental plant at Canaries (1893), Martinique (1882), Brazil (1871), Australia (1875/83) and New Zealand (1865) , it is possible that slaves and marooned slaves had their role in this species propagation at R\u00e9union; in fact, Hedychium spp. are identified among the food plants of marooned slaves from East Africa, Madagascar, and the Mascarene Islands Table . Concern5) Table . The ana5) Table and Grub5) Table , did not5) Table . FinallyRegarding the severity of these escapes Table to MauriThis research was only possible due to the valuable resources already available online, namely, the Herbaria digitalized specimens or the digitalized historical documents at Biodiversity Heritage Library and Internet Archive. However, although the word search tool is extremely useful to accelerate the research inside documents, in some situations the names are not detected, e.g. a lack of a letter due to digitalization quality, letters not perfectly printed or misspelt words or about the species distribution or even about the name authority. Moreover lacks of information were identified as the years of introduction of the species , or about the severity of its escapes in certain regions. Although Hedychium spp. are cultivated worldwide, there is a substantial paucity of studies about the presence and spreading of this species in Central and South America, Africa and several oceanic islands. Finally, H. gardnerianum is a serious pest in Azores, Madeira, Jamaica, R\u00e9union, New Zealand and Hawaii and continues to expand its distribution area in South and Central America, Australia and Southern Africa. The species continues to escape from cultivation as the recents escapes in Tenerife and Viti Levu islands and Galicia.In synthesis, this study updated the information about Hedychium spp. too. The same for several specially frequent trouble associations as H. gardnerianum plus Pittosporum undulatum .While in some regions two or three species of the genus are considered invasive (e.g. Brazil) in others although two species are considered escaped from cultivation one wined the invasive status above the other (e.g. Azores); a future analysis of expansion risk of this species should consider all the Hedychium gardnerianum is a validly published name, the authority of the name is Sheph. ex Ker Gawl., the species holotype is the illustration published along with the species name, and the Natural History Museum BM000574691 specimen collected in 1815 is the first dried specimen of H. gardnerianum; (b) This species is native to the Central and Eastern Nepal, Bhutan, Northeast India and North Myanmar; (c) The species was cultivated at Cambridge Botanical Garden since 1818 and the first known herbarium specimen collected in Europe dates back to 1821; (d) Kathmandu and Khasi Hills (India) specimens are considered two varieties of the same species and the BM000574691 specimen is the lectotype of H. gardnerianum var. speciosum; (e) Specimens, references, and/or pictures support that H. gardnerianum escaped from cultivation at Galicia (Spain), Azores archipelago, Madeira, Tenerife, Cuba, Jamaica, Martinique, Trinidad, Ascension, Mexico, Honduras, Brazil, South Africa, Swaziland, Zimbabwe, R\u00e9union, Mauritius, Australia, New Zealand, Fiji, Hawaii, and Vietnam; and (f) H. gardnerianum is a serious pest in Azores, Madeira, Jamaica, R\u00e9union, New Zealand and Hawaii and continues to expand its distribution area in South and Central America, Australia and Southern Africa.In summary, the analysis of the available information allowed to conclude that: (a)"} +{"text": "The aim of this Special Issue is to highlight the progress in the manufacturing, characterization, and applications of environmentally friendly polymeric blends from renewable resources.Materials from renewable resources have attracted increasing attention in past decades as a result of environmental concerns and due to the depletion of petroleum resources. Polymeric materials from renewable sources have a long history. They were already used in ancient times and later accompanied man along with the development of civilization. Currently, they are widespread in many areas of life and used, for example, in packaging, and in the automotive and pharmaceutical industries.Polymers from renewable resources are generally classified into three groups: (i) natural polymers, such as cellulose, starch and proteins; (ii) synthetic polymers from natural monomers, such as poly(lactic acid), and (iii) polymers from microbial processes, such as poly(hydroxybutyrate). The emergence of new methods and analytical tools provides a new level of understanding of the structure\u2013property relationship of natural polymers and allows the development of materials for new applications.One of the attractive properties of the natural polymers and synthetic polymers produced from natural monomers is their inherited biodegradability. On the other hand, this is related to their moisture sensitivity, which limits their application. Other important limitations of most polymers from renewable resources are their lower softening temperature and mechanical strength. These and many other properties of polymers can be modified and improved through the blending of two or more compounds, for example two or more polymers, polymers and fibers, polymers and nanoparticles etc.A blending approach, which may result in both polymer blends or composites, is an effective way to achieve a desirable combination of properties that are often absent in the individual components. Polymer blends and composites are useful as they can be produced from low-cost raw materials, including industrial waste products, without sacrificing their desired properties; they can also be used to prepare high-performance compounds for broader applications due to biodegradability and reusability of the end products.The final properties can be modified by changing the relative concentration and kind of monomeric units used in the synthesis or by varying the proportion of homopolymers and various additives in a blend composition. Development of effective methods of manufacturing products from blends of renewable polymers and environmental friendly synthetic polymers in a controlled way is the challenge of our time.synthesis of composites based on natural fillers;chemical modification of polymers or fillers in order to improve interfacial interactions;potential applications of the biobased materials.Accordingly, in this Special Issue of Materials, which is aimed at recognizing the current state of knowledge and development in the use of environmentally friendly polymeric blends from renewable sources, the following aspects were investigated:In this Special Issue, 13 original articles have been published on various topics, including the preparation, characterization, and some examples of uses of polymeric materials from renewable resources. This issue includes five articles on polyurethanes blended with various types of additives ,3,4,5, oMost of above papers pay particular attention to the role of eco-friendly fillers, i.e., microcrystalline cellulose, wood flower, lignin, rice straw nanofibers, lavender residues, sugar beet pulp, barley fibers, hemp shives, walnut shells, and curau\u00e1 fibers in the improvement of various properties in the final materials.In the papers of Cz\u0142onka, Str\u0105kowska et al., problems of polyurethane composites with different biofillers were discussed.In the paper \u201cPolyurethane Hybrid Composites Reinforced with Lavender Residue Functionalized with Kaolinite and Hydroxyapatite\u201d , blends In the paper \u201cRigid Polyurethane Foams Reinforced with POSS-Impregnated Sugar Beet Pulp Filler\u201d , blends In the paper \u201cImpact of Hemp Shives Impregnated with Selected Plant Oils on Mechanical, Thermal, and Insulating Properties of Polyurethane Composite Foams\u201d , materiaIn the paper \u201cRigid Polyurethane Foams Based on Bio-Polyol and Additionally Reinforced with Silanized and Acetylated Walnut Shells for the Synthesis of Environmentally Friendly Insulating\u201d , composi\u00ae Kraft Lignin for Liquid Sensing Applications\u201d [In the paper of Gon\u00e7alves, Rudnitskaya, Sales, Costa, Evtuguin polyureThe papers of Delgado-Aguilar et al. concerned eco-friendly blends derived from polyolefines.The paper of Delgado-Aguilar, Tarr\u00e9s, Marques, Espinach, Juli\u00e1n, Mutj\u00e9, and Vilaseca (\u201cExplorative Study on the Use of Curau\u00e1 Reinforced Polypropylene Composites for the Automotive Industry\u201d ) studiedIn the paper of Serra-Parareda, Tarr\u00e9s, Delgado-Aguilar, Espinach, Mutj\u00e9, and Vilaseca , barleyAnother two papers were devoted to synthetic resin reinforced with various bio-based fillers.In the paper of Chabros, Gawdzik, Podko\u015bcielna, Goliszek, and P\u0105czkowski , modifiIn the paper of P\u0105czkowski, Puszka, Miazga-Karska, Ginalska, and Gawdzik the proIn the paper of Alc\u00e1ntara, Gonz\u00e1lez, Pareta, and Vilaseca , cellulIn the paper of Wang, Liu, Duan, Xu, Zhang, She, and Zheng biocharThe papers of Du at al. and Goliszek at al. concern synthesis of sorbents based on natural components.In the paper of Du, Dong, Lin, Yang, and Zhao , quaterThe paper of Goliszek, Podko\u015bcielna, Sevastyanova, Gawdzik, and Chabros investiThe usage of polymer blends and composites, both prepared by blending, are two strategies used in the \u201cgreen\u201d requirements of many industries. Green chemistry strategies are mainly accomplished by reducing waste production, reducing raw material usage, reducing nonrenewable energy sources and overall energy demand, reducing risks, hazards, and costs. In this Special Issue, the great potential of agricultural and wood residuals, as they are or chemically modified, for the improvement of broad range of polymeric materials is clearly demonstrated. Cheap and abundant resources such as wood, rice straw, hemp, walnut shells, and other types of biomass and their constituents can improve the strength, thermal and some specific properties of final polymeric materials that have a great potential to be used in automotive, construction, and pharmaceutical and environmental protection industries."} +{"text": "Canarieae of the Burseraceae family, composed of trees and shrubs supplied with resin channels. Its uses in folk medicine are related to aromatic properties, which have numerous medicinal applications and are present in reports from traditional peoples, sometimes as the only therapeutic resource. Despite its economic and pharmacological importance in the region, and although the family is distributed in all tropical and subtropical regions of the world, most of the scientific information available is limited to Asian and African species. Therefore, the present work aimed to review the secondary metabolites with possible pharmacological potential of the species Trattinnickia rhoifolia Willd, popularly known as \u201cBreu sucuruba\u201d. To this end, an identification key was created for chemical compounds with greater occurrence in the literature of the genus Trattinnickia. The most evident therapeutic activities in the consulted studies were antimicrobial, antioxidant, anti-inflammatory, antiviral, antifungal, anesthetic and antiparasitic. An expressive chemical and pharmacological relevance of the species was identified, although its potential is insufficiently explored, mainly in the face of the NTDs present in the Brazilian Amazon.Plant-derived products may represent promising strategies in the treatment of Neglected Tropical Diseases (NTDs). From this perspective, it is observed that the Amazon phytogeographic region contains the tribe Over the years, natural products have been used as raw material sources in the synthesis of chemical compounds that result in new drugs, a good part of which are used in the treatment of Neglected Tropical Diseases (NTDs) . That isIn parallel to the biological variety found in the Amazon Forest, there are NTDs that encompass a group of 17 common infectious diseases in the region, including dengue, rabies, trachoma, buruli ulcer, endemic treponematosis, Hansen\u2019s disease (leprosy), American trypanosomiasis, African trypanosomiasis, cysticercosis, dracunculiasis, echinococcosis, foodborne trematode infection, lymphatic filariasis, onchocerciasis, schistosomiasis and soil-borne helminth infection, as well as leishmaniasis. Public health problems are also included, such as the human immunodeficiency virus (HIV)\u2014which causes the acquired immunodeficiency syndrome (AIDS)\u2014tuberculosis, malaria and other neglected infections. Thus, it is a heterogeneous group of diseases with serious social consequences, due to their high capacity for morbidity.NTDs affect more than one billion people worldwide, with greater severity in individuals submitted to socioeconomic vulnerability, generally belonging to underdeveloped or emerging countries. As a result, social, public health, productivity and life quality problems are intensified, particularly among marginalized populations. Amid the secondary factors related to the persistence of NTDs, the following stand out: (a) gaps in science and research, for presenting insufficient knowledge, non-related to these diseases, (b) market factors, such as high-cost drugs, in existing or developing vaccines, and (c) gaps in public health, represented by poor access to medicines and treatments as a consequence of failures in administrative planning, even when such services are offered for free .From this perspective, NTDs represent an enormous challenge for Brazil and other nations, since they are considered the infections with the highest levels of occurrence\u2014such as cutaneous or visceral leishmaniases, whether endemic or not. These diseases are heightened by their multiple forms of clinical manifestations, which depend on the pathogenicity of the infecting species. Its characteristics modalize leishmaniasis among its subclinical infections, with localized or disseminated microlesions, whether asymptomatic or not. In addition, wounds can spontaneously heal or progress from milder to more severe forms, which is why the WHO recommends priority treatment for this disease .Leishmaniasis is considered an important public health problem in the world and is one of the six most important infectious and parasitic diseases of NTDs, with an annual incidence of 2 million cases of different clinical forms, representing a risk to 350 million people in developing countries ,2.Sarcomastigophara, order Kinetoplastida and family Trypanosomatidae, which are responsible for morbidity and mortality in several countries in tropical zones. Seven species that cause tegumentary leishmaniasis have already been identified in Brazil, six from the subgenus Viannia and one from the subgenus Leishmania. The three main species are: L. (V.) braziliensis, L. (V.) guyanensis and L. (L.) amazonensis, and more recently, the species L. (V.) lainsoni, L. (V.) naiffi, L. (V.) lindenberg and L. (V.) shawi, identified in states in the North and Northeast regions [Leishmaniases are diseases caused by the protozoan of the genus Leishmania that are marked by great clinical pleomorphism. The parasites that cause them are included in the subkingdom Protozoan, phylum regions .Leishmaniases have factors that are increased by the virulence and dissemination of the protozoan, which depend on the host\u2013parasite relationship. This is because the manifestation of the disease is not only correlated with the species of parasite involved, but also with the susceptibility of the host, assessed by its immune response . FurtherDue to the incipience of first-line medicines and considering the potential of the Amazon, research in the areas of phytochemistry and ethnopharmacology are increasingly important to expand knowledge in strategic areas related to Research, Development and Innovation (RD and I) about traditional medicines. Hence, it is possible to create prototypes of promising new chemotherapeutic agents with anti-leishmanial activity, with minimized or non-existent side effects.Trattinnickia rhoifolia (T. rhoifolia), an angiosperm tree present in the biogeographic region that comprises Central America that belongs to the Burceraceae family, of the Canarieae tribe [Amid the promising Amazonian plants for such objectives, we highlight the species ae tribe ,8.Trattinnickia rhoifolia is used by traditional peoples to cure sore throats and skin lacerations, as well as to treat and prevent tumors and leukemia. To this end, the most used parts of the plant are the trunk bark, resin and leaves [The species d leaves .Trattinnickia, studies have already been carried out on photochemical mapping in the bark of the species Trattinnickia peruviana, which indicated the presence of lichen xanthone and triterpenes. Furthermore, triterpenes and sesquiterpene lactones were isolated in the resin of the species Trattinnickia aspera [Trattinnickia glaziovii [For the genus a aspera ,8,9. Addlaziovii ,8,9.T. rhoifolia, the focus of this study, triterpenes, monoterpenes, amentoflavones, sterols and sesquiterpene lactones have already been identified in different parts of the plant, such as resin, leaves and in the bark of its trunk [Regarding the species ts trunk ,11.Trattinnickia rhoifolia Willd and consequently of the genus Trattinnickia, which is a promising source for obtaining biopharmaceuticals from the production of secondary plant metabolites and, as a result, represents an opportunity in the field of drug innovation. For this reason, it is essential to know the research that addresses its main characteristics, such as taxonomic, ethnopharmacological and phytochemical studies, in order to direct future biological tests based on the bioactive action of the species Trattinnickia rhoifolia Willd.It is important to present the phytochemical mapping of the species Trattinnickia and the studies on their pharmacological potential. Data collection was carried out from September 2020 to May 2021, using the following databases: CAPES journals, PubMed, Science Direct from Elsevier, Wiley Online Library, Springer-Nature, Taylor and Francis, BMC, Hindawi, Scielo, ACS\u2014American Chemical Society, and Google Scholar, as well as the scientific article and patent databases \u201cThe LENS\u201d and \u201cORBIT Intelligence\u201d.In this sense, this study constitutes, methodologically, an analytical bibliographical review related to the mapping of secondary metabolites found in the genus The inclusion criteria for this work were: original articles and exclusive dissertations of the genus and species studied, with full text available in Portuguese, English or other languages. Exclusion criteria were: abstracts, online sites without scientific sources, incomplete texts, unrelated and repeated articles.Burseraceae, genus Trattinnickia and species Trattinnickia rhoifolia Willd, correlated with secondary metabolites and their pharmacological potential. The articles were selected by reading the titles and abstracts of publications, associated with the Boolean descriptor \u201cAND\u201d, in order to refine the samples.As for the search strategy, the descriptive words used in this work were: family Trattinnickia rhoifolia Willd, mainly due to reports of the use of the resin, bark and leaves of the plant by traditional peoples of the Amazon Region and, in this sense, assisting future studies that seek to understand and perform the chemical mapping of that species, highlighting its high pharmacological potential.Therefore, the innovation present in this study consists in elucidating the potential use of the species Trattinnickia rhoifolia and address the scarcity of studies on the classes of metabolites present in the studied species, which comes from the Burseraceae family.Hence, the review contributes to direct future studies that also prove the importance of evaluating the biological activities of the species Burseraceae family has 19 genera and more than 700 species [Boraginales, Dilleniales, Icacinales, Metteniusiales and Vahliales. Besides, this system suggests the inclusion of Burseraceae in the order Sapindales, class Dicotiledoneae and subclass Rosidae (APG IV 2016) [The species , composeBurseraceae distributed in South America, only 6 are native . In their turn, the other two (Dacriodes and Protium) were introduced and are representative in the Amazon Region [Burseraceae is the natural production of aromatic oleoresins, which are used regionally in alternative medicinal treatments and in the ethnopharmacology of Amazonian traditional peoples. The plant genera Dacryodes and Protium are popularly known as: \u201calmescla\u201d, \u201cbreu-branco\u201d, \u201cbreu-preto\u201d, \u201cbreu-vermelho\u201d, \u201cbreu-terra\u201d, \u201cbreu-lim\u00e3o\u201d, \u201c breu-manga\u201d, \u201ccara\u00f1a\u201d, \u201ccopal\u201d, \u201ccopal-ouro\u201d, \u201ccopal-negro\u201d, \u201celemi\u201d, \u201cmanila-elemi\u201d, \u201cfrankincenso\u201d, \u201cgugul\u201d, \u201cmaaliol\u201d, \u201cmirra\u201d and \u201cokume\u201d [Of the 19 genera of \u201cokume\u201d ,11,12.Burseraceae family is concentrated in the oil\u2013gum\u2013resin, from which fractions considered volatile are usually obtained [The mapping of the chemical compounds of the obtained ,12. In pobtained .The manipulation of the resin is historically common among the traditional peoples of the Amazon, who use it in the manufacture of varnishes and paints, along with boat-caulking. The aromatic constituents that are present in the resin, bark and branches of the plant are widely used through combustion, as well as for lighting the homes of traditional Amazonian peoples, as repellents for undesirable insects and also in religious rituals ,11,12,13Burseraceae family focus on the constituents present in its leaves, of which the monoterpenes represent the dominant class of compounds, distributed in limonene, \u03b1-phellandrene, p-cimene and their monocyclic derivatives. Aldehydes, ketones and acids are also present, though less frequently [Cryptococcus neoformans var. Neoformans\u2014a systemic human fungus of high prevalence in immunosuppressive patients [The chemical characterization studies of the equently ,15. In pequently ,13. Therpatients .Burseraceae family. The most common and complex are in the genera Canarium and Commiphora, except in the species Boswellia carterii. In those cases, cadinene is isolated in essential oils obtained from the leaves, as the substance is found in lower concentrations in other parts of some species of this family [Canarium, the elemol group was also isolated, which constitutes the synthesis of germacra (10), 4 diene, widely used to combat Phlebotomus\u2014the genus to which the agents that transmit malaria and leishmaniasis belong [There are similar chemical profiles that identify over 30 sesquiterpenes in the s family ,16. Froms belong ,17,18. TProtium leaves are rich in cariophilia, which is generally ubiquitous, and in sesquiterpenes, described as bactericides for the etiological agents that cause acquired respiratory infections, such as otitis, sinusitis and pneumonia [Burseraceae [Canarieae, isolations of furanosesquiterpenes are described, which are furanogermacrane skeletons, forming 2-acetyl-8-12-epoxygermacra-1, (10), 4,7,11 tetraene and 2-methyl-8-12-epoxygermacra-1, (10) 4,7,11-tetraene. It is noteworthy that the active ingredients of these molecules are sources used in the composition of antimalarials [On the other hand, essential oils from neumonia ,18,19. Sseraceae . In studalarials ,18,19, walarials ,18,20.Burseraceae resins, the existence of tetracyclic and pentacyclic triterpenes is identified. These compounds are responsible for important characteristics, such as oxidation, due to the presence of tetracyclic tirucallane in the C-17 side chain, which is found as elemolic acid. In the scientific literature, the anti-inflammatory activity and the inhibition of the production of nitric oxide are also reported, in addition to in vitro antitumor activity [Canarium schweinfurthii and Dacriodes eludis, species of the tribe Canarieae, in which the study related to the respective compounds proved the existence of anti-inflammatory, antimicrobial, antiplasmodic, antiulcerogenic, anticariogenic, antiviral, anti-HIV, hepatoprotective, cardioprotective and analgesic activities [In activity ,19,20. Ttivities ,21,22,23Burseraceae. Kaempferol, quercetin and their respective derivatives were identified in Protium and Commiphora [Burseraceae. However, coumarinolignoids and propacin have already been identified and isolated from Protium opacum\u2014compounds that have hepatoprotective, immunomodulatory and anticancer activities [Protium helio and P. icicariba stand out [In their turn, flavonoids are essential in plant systematics, but there were few technical-scientific reports found about these compounds in mmiphora ,22,23,24tivities ,25,26. Atand out .Burseraceae focuses mainly on pentacyclic triterpenes. The most abundant are the \u03b1-amyrin and \u03b2-amyrin isomers [Chemical research on the stem of the botanical family isomers , which h isomers ,13,20, w isomers .P. robustum, P. trifoliatum, P. nitidifolium and P. subserratum, collected in the Amazon region, identified sesquiterpenes in a higher percentage, as well as the following compounds: spatulenol, caryophyllene oxide, Khusimone, \u03b1-copaen-4-ol, and in smaller amounts, \u03b1-cubeben, \u03b1-copaene, trans-caryophyllene, \u03b1-trans-bergamothene, \u03b3-muurolene, \u03b1-muurolene, \u03b3-cadinene [trans-caryophyllene, \u03b1-elemene, \u03b1-gurjunene, germacrene D, \u03b1- and \u03b2-selinene, cis-calamenene, trans-calamenene and cadalene [The studies carried out using stems, branches and bark of the species cadinene ,20, \u03b1-cacadalene ,20,28,29Burseraceae, but coumarinolignoid and propacin have already been identified and isolated from the species Protium opacum [The literature also describes the presence of aromatic compounds such as coumarins, phenylpropanoids, flavonoids and, to a greater extent, lignans, which demonstrates the biological potential of the family ,18. TherTrattinnickia rhoifolia Willd is popularly known in the Amazon region as \u201cBreu sucuruba\u201d. Its native origin is not endemic to Brazil, but T. rhoifolia Willd has an Amazon phytogeographic occurrence [Plantae, phylum Tracheophyta, class Magnoliopsida, order Sapindales, family Burseraceae, genus Trattinnickia and species Trattinnickia rhoifolia, which has wide ethnopharmacological use by indigenous peoples , digitized base and cylindrical shaft. In addition, it has a grayish rhytidome with depressions and detachment in small woody plaques, which leave light streaks, lenticels are present, 2 mm thick dead brown skin and 1 cm thick bright orange skin. Orange sapwood has transparent exudation with a \u201cbreu\u201d smell [The species u\u201d smell ,12,18.Trattinnickia rhoifolia Willd is more predominant in the upper parts of the species, so that only the aromas attributed to the presence of terpenes are uniform. Due to this characteristic, the resin is used to combat some species of insects from the Psicodidae and Culicidae families. As a result of this practice, there is a reduction in the prevalence of malaria and leishmaniasis in indigenous villages and riverside communities [Trattinnickia are widely known in the Amazon region by popular medicine as repellent, analgesic, anti-inflammatory, expectorant and healing plants [The distribution of the aromatic resin present in the species munities ,30,32,33g plants ,13,20,34Trattinnickia in parasitic diseases such as leishmaniasis [Nonetheless, scientific research that demonstrates its performance is incipient or almost non-existent, as illustrated by the scarcity of studies on the action mechanisms of species of the genus maniasis .Burseraceae family has extensive chemical mapping and demonstration of its pharmacological properties, proven by its anti-inflammatory, antimicrobial, antiparasitic and antifungal activities. However, there are few studies regarding the identification of compounds for the genus Trattinnickia [Studies involving eicosane and nonacosane produced important antiparasitic effects against strains of or cells ,39. In tnthrene) .Trattinnickia rhoifolia, the existence of amentoflavan was identified, also found in oil-resins, 5\u03b1, 6\u03b1 epoxy-\u03b2-sitosterol (IV) and 5\u03b2, 6\u03b2-epoxy-\u03b2-sitosterol (V) [In studies on extracts from the leaves of erol (V) ,46. Besierol (V) .From this perspective, the authors have reported that amentoflavone acts in favor of the inhibitory activity of cAMP phosphodiesterase, among other enzymes. The process of inhibiting these mechanisms results in tissue regeneration ,45. FurtTrattinnickia, which belongs to the Burseraceae family, represents an important ethnopharmacological source widely used by traditional peoples in the Brazilian Amazon due to its cultural and cosmological attributes in the treatment of Neglected Tropical Diseases, related to anti-inflammatory processes and antiparasitic and repellent functions.The extensive bibliographical research revealed that the genus Trattinnickia rhoifolia are similar to the traditional use of the species, which associates the following properties to the \u201cbreu scuruba\u201d: anticancer, anti-inflammatory, antimicrobial, neurological and antiparasitic, all attributed to the phytochemistry of the genus.The reviewed scientific literature indicates that the biological activities of The main classes of secondary metabolites, already characterized both in number of compounds and in pharmacological and environmental importance, are: alkaloids, terpenoids, sesquiterpenes, flavonoids, biflavonoids, oxyphytosterols and volatile oils. However, scientific support is restricted to mappings available for Asian and African genera, and studies on the subject are limited to these continents, even though the family is distributed in several tropical and subtropical regions of the world.Trattinnickia as a multipurpose drug related to its pharmacological groups, there are several limitations in the current literature, especially with regard to studies for the species Trattinnickia rhoifolia Willd. On the other hand, popular knowledge bases are important to recognize that traditionally used extracts of the species Trattinnickia rhoifolia Willd can be effective not only when isolated or in direct use, but can also represent new and promising alternatives, with modulating effects when used in combination with other herbs or drugs.Although the results of this review are very promising for the use of the genus Trattinnickia rhoifolia Willd is essential for further work because of the importance of the results raised here, especially given the pharmacological potential of the group, which should be better explored\u2014especially concerning the use of the species for its anti-inflammatory and analgesic activities, as reported by traditional communities in the Amazon region and presented in this article.Therefore, studying the species"} +{"text": "The article, Indications for fertility preservation not included in the 2017 Japan Society of Clinical Oncology Guideline for Fertility Preservation in Pediatric, Adolescent, and Young Adult Patients treated with gonadal toxicity, including benign diseases written by Masanori Ono, Kimikazu Matsumoto, Narikazu Boku, Nobuharu Fujii, Yumi Tsuchida, Tatsuro Furui, Miyuki Harada, Yoshinobu Kanda, Akira Kawai, Mitsuru Miyachi, Atsuko Murashima, Robert Nakayama, Hiroyuki Nishiyama, Chikako Shimizu, Kazuhiko Sugiyama, Yasushi Takai, Keishi Fujio, Ken\u2011Ichirou Morishige, Yutaka Osuga, and Nao Suzuki was originally published Online First without Open Access.http://creativecommons.org/licenses/by/4.0.With the author(s)\u2019 decision to opt for Open Choice the copyright of the article changed on February 16, 2022 to \u00a9 Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The original article has been corrected."} +{"text": "Housing is one of the major determinants of human health and the current COVID-19 pandemic has highlighted its relevance. The authors summarize the main issues, including dimensional standards, indoor air quality, safety, accessibility, neighborhoods, and area characteristics. The authors propose an operating scheme in order to implement actions to improve residential wellbeing on a local, national, and international level. Our readers might wonder, why another special issue on housing and health? Is it really necessary to study and work on the relationships between housing and human health? Is it still a relevant issue in today\u2019s world? We are quite sure that the answer is yes, because housing was, is, and will remain a central theme for public health worldwide. We must strengthen our knowledge to ensure the best and healthiest living condition for the entire world population. We therefore strongly need new research on this topic, not just to evaluate the current situation in different countries and contexts, but also to be able to validate new solutions aimed at improving the health standards of housing and making them suitable and affordable for a larger portion of the human population.-Dimensional standards-Indoor air quality-Safety-Accessibility-Neighborhoods and area characteristicsHousing represents a core and traditional topic of public health , despiteRelevant classical issues such as thermal and hygrometric comfort, lighting, noise protection, water supply, and waste disposal have a strong impact on both psychological and physical health of inhabitants. Despite being widely recognized as key factors for healthy living environments at both scientific and legislative levels, these factors are not adequately guaranteed in all dwellings worldwide ,17,18,19Sufficient dimensional area is a key determinant for healthy housing . AccordiIndoor air is an historical and widely recognized health determinant ,48,49,50Despite a lack of reliable epidemiological data on a global basis, home accidents are among the leading causes of death, infirmity, and disability worldwide, in both developing and developed countries ,88,89. TAmong emerging safety issues, we would also include structural problems related to extreme natural phenomena, such as floods, tsunamis, earthquakes, landslides, volcanic activities, and heat and cold waves. In the last few years, several catastrophic events have occurred around the globe, causing many victims ,102,103.per se, the elderly are more fragile and susceptible to the harmful effects of their dwellings; therefore healthy ageing is a goal for an economically and socially sustainable future [The aging population faces increasing morbidity, multi-morbidity, functional limitations, and disability ,109. Alte future ,114,115.e future ,117. Thee future ,119,120.e future . AccessiAs is already widely expressed in international literature, the concept of healthy housing also implies a residential setting that can fulfill the expectations of its residents ,122. In -Research, to consolidate evidence on the main health threats in indoor environments and to create strategies to mitigate their effects, as well as elaborating on guidelines and standards;-Education, to spread research-acquired knowledge not only to health sector workers, but to engineers and architects, lawmakers, public administrators, and the general population (directly or via relevant stakeholders);-Lawmaking, to enforce research-based regulation, as it is recognized as key part of health protection in built environments [ronments ,142,143;-Policy, to provide political and financial support to housing in local, national and international programs;-Evaluation and control, to obtain a constant monitoring of implemented housing campaigns in input, output, and process validated indicators, and control of local health authorities on hygienic standards application.As housing is a leading health determinant, improving living conditions in both economically developed and developing countries may reduce mortality and burden of disease, and increase health quality from a physical, psychological, and social point of view ,50,139. To successfully implement these proposals, which we may call RELPE actions, strong commitment and functional coordination and harmonization is needed at a local, regional, national, and international level, providing the involvement of researchers, educators, public health operators, building designers, urban planners, lawmakers, communities, and representative associations.Housing is a key determinant for human health. We have tried to summarize some of the major factors connecting housing and health, citing the most relevant scientific evidence currently available, that shows a strong relation with social and economic conditions; however, it is often very difficult to assess their independent effect . The COV"} +{"text": "In the published article, there was an error in the affiliations. Instead of Qilu Hospital, Shandong University, Jinan, China, it should be:1 Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China2 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China3 Department of Emergency, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.YL is affiliated with 1, LW is affiliated with 2, JZ is affiliated with 1, HH is affiliated with 1, HL is affiliated with 1, CL is affiliated with 2, HG is affiliated with 1, YC is affiliated with 3, XC is affiliated with 1.Furthermore, Lin Wang was not included as a co-first author in the published article. This has been corrected, and a new statement has been added to indicate that Yuan Li and Lin Wang contributed equally: \u201cThese authors contributed equally to this work.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Rothrauff, Lars Engebretsen, Andrew D. Lynch, Olufemi R. Ayeni, Mark V. Paterno, John W. Xerogeanes, Freddie H. Fu, Jon Karlsson, Volker Musahl, Eleonor Svantesson, Eric Hamrin Senorski, Thomas Rauer, Sean J. Meredith, The Panther Symposium ACL Treatment Consensus Group, was originally published Online First without Open Access. After publication in volume 28, issue 8, page 2390\u20132402 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to \u00a9 The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit"} +{"text": "Utricularia includes around 250 species of carnivorous plants, commonly known as bladderworts. The generic name Utricularia was coined by Carolus Linnaeus in reference to the carnivorous organs (Utriculus in Latin) present in all species of the genus. Since the formal proposition by Linnaeus, many species of Utricularia were described, but only scarce information about the biology for most species is known. All Utricularia species are herbs with vegetative organs that do not follow traditional models of morphological classification. Since the formal description of Utricularia in the 18th century, the trap function has intrigued naturalists. Historically, the traps were regarded as floating organs, a common hypothesis that was maintained by different botanists. However, Charles Darwin was most likely the first naturalist to refute this idea, since even with the removal of all traps, the plants continued to float. More recently, due mainly to methodological advances, detailed studies on the trap function and mechanisms could be investigated. This review shows a historical perspective on Utricularia studies which focuses on the traps and body organization.The genus Utricularia species (bladderworts) are one of the most fascinating carnivorous plants, with tiny traps and seemingly no roots [Utricularia species usually do not follow traditional models of morphological classification. The body organization of Utricularia does not present clearly defined boundaries between ordinary plant organs , or recognizable roots [no roots ,5,6,7,8.no roots ,12,13,14Utricularia were most likely by Conrad Gessner (1516\u20131565), a Swiss physician and naturalist, in his Historia Plantarum, also called Conradi Gesneri Historia Plantarum [Libri Picturati, , there is one of Utricularia which is accessible at the Jagiellonian Library of the Jagiellonian University in Krak\u00f3w [Utricularia vulgaris [Hortus Malabaricus in 1689 [Utricularia reticulata as \u201cNelipu\u201d (Utricularia to be referenced before Carolus Linnaeus (1707\u20131778), the founder of modern taxonomy, who proposed the genus Utricularia and described seven species in his Species Plantarum [U. vulgaris, U. minor, U. subulata, U. gibba, U. bifida, U. caerulea, and U. foliosa. The U. caerulea treated by Linnaeus was a blend of different taxa [U. caerulea by Linnaeus himself [The earliest illustrations of Gessner 16\u20131565, vulgaris , in whic in 1689 , Hendric\u201cNelipu\u201d A, a Malalantarum : U. vulgent taxa ,20, reprUtricularia was coined by Linnaeus in reference to the traps which are the carnivorous structures present in all species of the genus from aquatic to terrestrial environments [Utricularia by Linnaeus, many species have been described. In particular, Vahl [Utricularia, mostly by Rafinesque [Utricularia by other authors [The generic name ronments ,22. The ronments . Since tar, Vahl , Brown [ar, Vahl , Smith [ar, Vahl , Saint Har, Vahl ,28,29,30ar, Vahl contribuar, Vahl . Severalfinesque , who bas authors .Utricularia after dedicating four decades of his life to the bladderworts. Taylor\u2019s [Utricularia species: the Indian U. tayloriana [U. hirta), and the Australian U. petertaylorii [In 1989, Peter Geoffrey Taylor 1926\u20132011), a British botanist who worked at the Royal Botanic Gardens, Kew, published his magnificent monograph about the genus 11, a Briyloriana , synonymtaylorii . To datetaylorii .Utricularia has been highlighted as unique in many studies of Lentibulariaceae and s , lithophytic , rheophytic , and some aquatic species have \u201crhizoids\u201d [U. aurea, U. breviscapa, U. inflata), a whorl of floats is found at the inflorescence base, resembling swollen shoots filled with aerenchyma cells and lacunae, and with appendages similar to branched shoots. These structures provide stability to the inflorescence, keeping it above the water table and making it more conspicuous to pollinators [All al roots . Some spal roots ,48). Manhizoids\u201d , which chizoids\u201d ,49. In slinators ,35,50.Utricularia shows organs with intermixed morphological traits of organ categories , and homologous to shoots. This was especially evident to the authors in the dimorphic leaves of U. dusenii , few anatomical characters typical for roots are present in stolons and root , the ves e.g., ,8). For . For Utrs , of whiu Taylor postulaton\u201d, cf. ,54. Simistolons is best known for his The Origin of Species [The Origin of the Species, Darwin wrote: \u201cI care more about Drosera than the origin of all the species in the world\u201d. That sentence became more understandable when, after fifteen years, he published his Insectivorous Plants [Utricularia traps.The bladderwort\u2019s trap is one of the most complex and intriguing structures among living plants D and is Species , he pass Species to the Ss Plants , which wUtricularia are similar in general organization and structure, they arise from different parts of the plant in different species: from the petiole and lamina of the leaves, from the base of inflorescences, and/or from stolons and their branches. The traps are foliar structures shaped as globose or ovoid vesicles (bladders) with a length of 0.2 to 12 mm [U. breviscapa, U. foliosa, and U. gibba), the mature traps are even dark violet, most likely due to the presence of bacteria [Although the traps of to 12 mm ,21,59,60bacteria ,62 or anUtricularia and hypothesized the presence of a polarity from stalk to mouth by analyzing the trap glands. Impressively, by controlling the adaxial\u2013abaxial domains of gene activity for growth orientation in proximodistal and orthoplanar polarity in the primordia of U. gibba, simple shifts in the expression of genes homologous to the adaxial expressed PHV/PHB genes and abaxial expressed FIL and KAN genes [Trap development has been the subject of several studies that attempted to anatomically and genetically understand the processes that result in such a complex structure , usi, usiUtria e.g., ,84,85). ,85. Utria nt roots . Furthernt roots . Recent nt roots ,91,92,93nt roots . Moreovent roots . In thisnt roots ,97. Accont roots , the traUtricularia are needed to better understand the different observed patterns of seedling development, vegetative structures, and possible adaptations, from an evolutionary and phylogenetic perspective.Despite of some studies on post-seminal development ,104,105,Utricularia lineages and thus explain the differences of traps among the taxa .Utricularia and Genlisea and their evolutionary aspects [Utricularia genomes are comparable to those of other higher plants, with the noncoding DNA and transposable elements being the main responsible for genome size discrepancies [U. vulgaris transcriptome, and some of them are also present in the U. gibba genome [U. gibba, with the heterotopic transfer of the function of root genes to other organs [U. gibba genome indicated the absence of homologs of the WOX5 gene [Utricularia were explored, putative domains of WOX genes were identified . The development of genetically transformed Utricularia, as already proposed for U. gibba [Studies showing the minute sizes of chromosomes and geno aspects ,100 (Figepancies ,102, it epancies or morphepancies , are prea genome ,120. Accr organs . SimilarOX5 gene ,122, whiOX5 gene , but theU. gibba , could bUtricularia, particularly with the sampling of different life forms, and the inclusion of Genlisea as the other member of the rootless clade in Lentibulariaceae.However, to overcome this gap, and to advance in these important issues related to morphology simplification and loss of roots in Lentibulariaceae, we need a more complete scenario comprising more genomes and transcriptomes for"} +{"text": "We aim to conduct a scoping review focused on identifying approaches to documentation burden measurement and their characteristics.Electronic health records (EHRs) are linked with documentation burden resulting in clinician burnout. While clear classifications and validated measures of Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews (ScR) guidelines, we conducted a scoping review assessing MEDLINE, Embase, Web of Science, and CINAHL from inception to April 2020 for studies investigating documentation burden among physicians and nurses in ambulatory or inpatient settings. Two reviewers evaluated each potentially relevant study for inclusion/exclusion criteria.burnout.Of the 3482 articles retrieved, 35 studies met inclusion criteria. We identified 15 measurement characteristics, including 7 effort constructs: EHR usage and workload, clinical documentation/review, EHR work after hours and remotely, administrative tasks, cognitively cumbersome work, fragmentation of workflow, and patient interaction. We uncovered 4 time constructs: average time, proportion of time, timeliness of completion, activity rate, and 11 units of analysis. Only 45.0% of studies assessed the impact of EHRs on clinicians and/or patients and 40.0% mentioned clinician Standard and validated measures of documentation burden are lacking. While time and effort were the core concepts measured, there appears to be no consensus on the best approach nor degree of rigor to study documentation burden.Further research is needed to reliably operationalize the concept of documentation burden, explore best practices for measurement, and standardize its use. We evaluated all relevant literature identified through in-text references among eligible studies. Burden is not specifically represented in Medical Subject Headings (MeSH); therefore, we explored both keyword and MeSH terms for 2 burden-related concepts outlined in the HHS report We selected inclusion and exclusion parameters a priori, and iteratively modified them to exclude studies involving niche clinical systems and those strictly comparing to paper-based documentation . We inclThe term \u201cphysicians\u201d encompassed attending physicians, fellows, resident physicians, and interns; \u201cnurses\u201d referred to registered nurses. We focused on physicians and nurses given our aim of identifying interprofessional measurements of documentation burden. We excluded studies comparing EHR documentation to paper-based systems if they were not focused on measuring burden, but rather on EHR implementation evaluation.After removing duplicates, 2 reviewers independently screened article titles and abstracts for relevance using Covidence.One author (AJM) performed data charting for all articles meeting full-text inclusion criteria , Embase (n\u2009=\u20091143), Web of Science (n\u2009=\u20091007), and CINAHL (n\u2009=\u2009825). Seven additional manuscripts were identified through in-text references. After eliminating duplicates, 1946 titles/abstracts were screened; of those, 166 were eligible for full-text review. Consensus was achieved for all disagreements concerning the inclusion of full-text articles. Thirty-five studies meeting criteria were summarized in the final analysis .,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Studies were conducted in the United States (n\u2009=\u200931),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Articles were published between 2010 and 2020 with 2018 (n\u2009=\u20098),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Thirty were strictly quantitative studies. While purely qualitative studies were excluded, 5 studies employed mixed methods,,,,,,,,,,,,A diversity of analytical methods was employed. Most studies to which statistical testing were relevant (n\u2009=\u200923) applied parametric (n\u2009=\u200919) as opposed to non-parametric methods (n\u2009=\u200912). Qualitative methods employed in the mixed-methods studies involved informal interviews,effort constructs emerged gen,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Time spent documenting was assessed in all studies and was measured using 3 key data collection strategies: EHR usage logs (n\u2009=\u200928),,,,,,,,,,,,,,,,,,Less than half the studies assessed the impact of documentation burden on clinicians and/or patients (n\u2009=\u200916). Among those studies, authors referenced the temporal relationship between burden and burnout at a higher proportion (68.8%) compared to those that did not extend beyond measuring time and effort alone (50.0%). Outcomes measured included clinical process measures [n\u2009=\u20098 generalizability due to constraints in sample size (n\u2009=\u200919),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,measurement error including the inability of logs to distinguish between \u201cidle and active\u201d time (n\u2009=\u20096),,,,,,,,,,,,,,,,,,,,,,,,,,Two limitations were ubiquitous across included studies : (a) thr,,,,,,,,,,,,,,,,,,,,,,Six studies cited selection bias derived from both the presence of self-selection and voluntary participation among high-performing subjectsworkflow fragmentation and cognitively cumbersome work \u2014largely align with \u201cproposed core EHR use measures (for practice efficiency)\u201d published by Sinsky and colleagues which indicates burden may be quantified through existing metrics.In this scoping review, we identified 35 studies that explored the measurement of documentation burden among physicians and nurses, underlining the overall paucity of research in the domain. As may be expected, all 35 studies were published post-HITECH Act. Seven effort constructs, 4 time constructs, and 11 units of analysis were uncovered. Our effort constructs\u2014except ,,,,,Historically, TM studies have been considered the gold standard for quantifying the effects of computer systems on task-based clinical workflow and duration.,,,,,burden and a plethora of definitions throughout the literature.,,,,,,,,time and effort, such as workload,,,,burnout is identifiable in controlled vocabularies including, the International Classification of Diseases (ICD), in addition to the Diagnostic and Statistical Manual for Mental Disorders (DSM) and MeSH.,,time.One major finding of this review was the absence of quantitative studies assessing the reliability and validity of time and effort measures. Of the 35 studies included, only 1 study intended to develop a measure of burden ,Strategy on Reducing Burden Relating to the Use of Health IT and EHRs\u2014aims to evaluate the clinical impact of burden on clinicians and/or patients;The HHS Report\u2014,,,,,In this review, scribes represented 1 of 3 areas of study concerning proposed interventions to mitigate burden (n\u2009=\u20093);effort constructs, 4 time constructs, and 11 units of analysis our keywords were limited, and/or (b) our queries were not sufficiently broad or narrow.While this study sought to investigate literature on the operationalization of documentation burden and the development and/or validation of quantitative burden measures, research in this domain has not yet matured. Despite employing broad search terms and queries, the majority of the literature retrieved did not detail how to conceptualize and/or measure burden. We extracted manuscripts using keywords, as extant MeSH terms were unable to capture the phenomenon of study interest; in fact, no term for after scheduled duty hours measure described by Cox and colleagues should undergo rigorous testing and validation across settings and specialties.,,Future research should build upon existing burden evidence, focusing on strengthening objectivity and generalizability. Proposed quantitative measures of burden such as the ,,task value, as indicated by task relationship with burden, a high priority area for future research. Such research would allow the identification of tasks that are of high burden but low value so that EHR design and intervention efforts may target the elimination or mitigation of these tasks.However, promisingly, burden measures identified were not strictly unique to individual professions and workflows, supporting the opportunity for defining interprofessional measures of burden in future work. We propose that burden be examined as a global composite measure, indicative of magnitude and directionality, consistent with the characteristics uncovered in this review. This would require: (a) developing a universally agreed-upon inventory for key EHR tasks and activities weighted for relative value according to burden that could be linked to clinical outcomes such as \u201cquality, financial or professional satisfaction\u201dDocumentation burden among interprofessional clinical roles remains understudied and under-measured in both inpatient and ambulatory settings. This review suggests that concrete, validated measures of burden in research are lacking, which pales in comparison to burnout literature.This study was supported by the US National Library of Medicine of the National Institutes of Health (NIH) under the training fellowship award 5T15LM007079 and the National Institute for Nursing Research (NINR) under grant numbers 1R01NR016941 and 5T32NR007969.AJM and SCR conceptualized the scope of this review. AJM, JMS, RC, SS, and EL conducted the initial and full-text screenings. AJM drafted the manuscript with significant revisions and feedback from JMS, RC, KDC, and SCR.Journal of the American Medical Informatics Association online.The data underlying this article are available in the article and in its online None declared.ocaa325_Supplementary_DataClick here for additional data file."} +{"text": "Phthalates are a group of chemicals used in a multitude of important industrial products , mainly as plasticizers to improve mechanical properties such as flexibility, transparency, durability, and longevity of polyvinyl chloride (PVC). The wide occurrence of phthalates in many consumer products, including foods brings that most people are exposed to phthalates every day, which raises some concerns. Adverse health outcomes from phthalates exposure have been associated with endocrine disruption, deformities in the human reproductive system, increased risk of preterm birth, carcinogen exposure, among others. Apprehension related to the health risks and ubiquitous incidence of phthalates in foods inspires the development of reliable analytical approaches that allow their detection and quantification at trace levels. The purpose of the current review is to provide information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. Moreover, an overview of emerging extraction procedures and high-resolution analytical approaches for a comprehensive quantification of phthalates is presented. Phthalates, generally known as phthalate esters PAEs, , are a fBesides being easily released into the environment, they are rapidly biodegraded and photodegraded, leading to a lower persistence.The most common exposure routes of phthalates are: (i) personal care products ; (ii) food contact plastics ; (iii) sFrom the described potential routes, food and beverage constitute, undoubtedly, the most important source of human exposure to phthalates ,9. PartiThe phthalates are naturally released into the environment through their production, use, and/or disposal, and therefore can be absorbed by the human body by different routes , as seen in According to Bennett et al. , exposurIn the following sections, we provide descriptive information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. An overview of the emerging extraction procedures and analytical approaches for a comprehensive quantification of phthalates is also discussed. For this purpose, the keywords \u201cphthalates\u201d, \u201cPAEs\u201d, \u201cenvironmental\u201d, \u201cfood\u201d, \u201chealthy risks\u201d, \u201cextraction technique\u201d, and \u201canalytical platforms\u201d were researched in Pubmed, Scopus, Web of Science, and Google Scholar over the period of 2015 to 2021. It should be pointed out that other references were included outside of the established period due to their relevance to this review.As previously mentioned, PAEs are a class of synthetic chemicals mainly obtained from petroleum and added to an enormous number of everyday products. PAEs, linear and branched, are added to improve the properties of plastic materials . Lately,Due to the widespread use of these types of compounds and their immense applications, there is a potential risk, for both children and adults, of being exposed to phthalates. Phthalates are relatively released from the products into the environment due to the weak chemical bond between phthalates and other chemicals due to their dipolar interactions .Maternal diet and food preparation practices, such as maternal prenatal high-fat milk consumption was associated with higher benzyl butyl (BBz) and DEHP . The preNon-dietary exposure is another source, where they can be emitted from materials into the air and easily partitioned into the indoor and outdoor environment. Different phthalates have been detected, such as DEHP, diisobutyl phthalate (DiBP), and di-n-butyl phthalate (DnBP) in soil dust . The draThere are numerous studies where it has been shown that phthalates can alter the endocrine system and induce a plethora of effects such as carcinogens, teratogens, and mutagens ,32.Many phthalates, even at a low concentration, are known endocrine disruptors that havPhthalate exposure in humans has been linked to metabolic changes, such as increasing obesity problems (metabolic syndrome) and the Some other studies have concluded there is a relationship between phthalate accumulation and breast cancer . FurtherSeveral mechanisms have been proposed to explain the increase in blood pressure in pregnancy due to exposure to phthalates, namely an increase in oxidative stress, a decrease in serum thyroxin, and an increase in inflammatory cytokines, which could promote gestational hypertension or preeclampsia development ,45,46,47Due to the generalized exposure of phthalates, as mentioned above, in a great diversity of products, both at a domestic and industrial level, the different international health agencies had to regulate the levels of these chemical contaminants.In the United States, the Environmental Protection Agency (EPA) regulated the presence of eight compounds, namely DBP, DiBP, BBP, di-n-pentyl phthalate (DnPP), DEHP, di-n-octyl phthalate (DnOP), DiNP, and diisodecyl phthalate (DiDP) in consumers ,38, restPAEs are a group of chemicals that are widely used as plasticizers ,60,61. IFood contaminants can also occur with the migration of PAEs from packaging to food. In that sense, Arfaeinia et al. investig2 of DEHP and 0.86 \u00b5g/cm2 of DiNP, plastic filter holders releases maximum leaching of 2.49 \u00b5g\u2009/cm2 of DBP from polytetrafluoroethylene (PTFE) and Parafilm\u00ae leached levels up to 0.50 \u00b5g/\u2009cm2 of DEHP. To reduce the high levels of PAEs in these materials, a heat or high-temperature process was applied since there is no covalent bond between the PAEs and plastics. Tienpont et al. [2SO4), and DiBP and DEHP were found at trace concentration (ng/g) in alumina and Na2SO4. These authors also measured the PAEs concentration in the commercial solvents , DCM, and acetonitrile (MeCN)), being DEP (0.01 to 0.03 ng/mL), DiBP (0.002 to 0.21 ng/mL), DBP (0.01 to 0.80 ng/mL), di-n-hexyl phthalate , benzylbutyl phthalate , and DEHP (0.28 to 6.39 ng/mL) found in all solvents. The presence of these PAEs in solvents can be reduced by redistillation and/or by SPE [Special attention should be given to the sample preparation step as the sample can certainly be contaminated with laboratory material such as solvents , sorbents , plastic consumables , glassware, laboratory air, fibers, stir bar, among others ,118. Thit et al. verifiedr by SPE . The phtr by SPE . Neverthr by SPE , all matEfficient pre-concentration and clean-up procedures are necessary to guarantee the quality of the analytical methods, due to the predictable low concentration of these target analytes in samples, as well as the sample complexity . Table 22SO4 [In the LLE procedure, the sample is put in contact with a solvent with a high affinity to PAEs, followed by phase-separation caused by solvent properties, centrifugation, and removal of moisture by treatment with Na2SO4 . In gene2SO4 ,64,66,992SO4 , MeCN [92SO4 ,91,106, 2SO4 ,77,95,962SO4 ,125. DLL2SO4 ,105, as 2SO4 . The dat2SO4 , as a mo2SO4 ,87 used 2SO4 and 150 2SO4 used dee2) [Other extraction techniques used in the determination of PAEs are Soxhlet and SPE. Nevertheless, these extraction techniques are time-consuming, require solvents, and extensive sample handling , which i2) as adsorIn contrast to LLE, soxhlet, and SPE, SPME comprises sampling, extraction, purification, concentration, and injection into a single procedure. This extraction procedure is solvent-free, does not need previous sample preparation, and consequently, the risk of cross-contamination from solvents, samples, and glassware was reduced . SPME fi3O4) nanoparticles to extract 10 PAEs from milk. The data obtained, with recoveries ranging from 82% to 112%, and LODs and LOQs lower than 19 and 63 ng/L for all target analytes, supported the successful application of this modified QuEChERS-dSPE approach.QuEChERS-dSPE is an extraction technique that comprises two stages, namely extraction and clean-up. The extraction relies on the partitioning via salting-out extraction where an equilibrium between an aqueous and an organic layer was endorsed, while the clean-up by dSPE used various mixtures of porous sorbents and salts to eliminate matrix interfering compounds . QuEChERThe selection of the most suitable analytical approaches to separate, detect and identify a class of target compounds depends essentially on their physic-chemical properties and the sensitivity requested. As can be observed in 3) or silylation (-COOSiR3) process of the carboxylic acid group [Gas chromatography is the most used analytical approach for PAEs determination since these target analytes present low molecular weight , relatively low polarity, and thermally stable and appropriately volatility . In the id group . Neverthid group . Generalid group ,100,103.id group ,78,87. Cid group ,97, wateid group ,115,117 id group , but FIDid group ,114,125.id group ,100,127,id group , bromoprid group have alsid group . Furtherid group ,102,127 id group have alsid group ,100,112,id group ,78 and tid group ,102,127 id group ,69,103, id group ,100,112 id group ,102,127 In summary, the main advantages of GC-MS are high sensitivity (low LODs), especially by splitless injection, high reproducibility of the generated mass spectra by EI, low cost, ease of operation, requires less maintenance, and the identification of compounds is easier due to the available spectra libraries .GC is possibly the most used analytical platform in PAEs analysis. Liquid chromatography (LC) appears as a suitable alternative due to its potentiality in the analysis of thermally unstable and non-volatiles compounds providing a high selectivity . High-peIn summary, LC-MS offers several benefits in comparison to GC-MS, such as being faster, not requiring derivatization, minimal sample preparation, and facilitating the identification and quantification of a greater diversity of compounds . MoreoveThe wide occurrence of phthalates, mainly PAEs, in many products has contributed to the rising concerns about their effects on human health. Nevertheless, the health impacts of PAEs exposure are not completely elucidated. This fact highlights the need for the development of sample preparation and analytical approaches with the purpose of quantifying these target compounds with more accuracy. The evolution of sample preparation has been focused on quickness, simplicity, automatic, low sample handling, low solvent volume, use of green extractant with the aim to reduce the risk of cross-contamination from solvents, samples, and glassware, and also environmentally friendly. The most common extraction techniques used for the measurement of PAEs are LLE and SPME. Regardless, SPME compared to LLE presents several advantages such as being solvent-free, easy to operate, and comprising sampling, extraction, purification, concentration, and injection into a single procedure. Regarding analytical approaches, GC coupled with MS is the most used for the quantification of PAEs, as a result of their well-known volatility. Satisfactory figures of merit in terms of recoveries, accuracy, LODs, and LOQs, was obtained to demonstrate the success of GC-MS in PAEs determination. Despite this fact, a direct UHLC-MS/MS has also been used in PAEs determination with excellent results.The determination of PAEs in samples represents an inspiring task, not only because of the low concentration of these target compounds but also due to the complexity of the sample and the potential risk of cross-contamination during all steps of the analysis. This problem can be minimized by avoiding extraction techniques that require solvents and only using glassware. However, prior to analysis, all glassware should be submitted to washed soaking in an alkaline solution for 48 h, rinsed with purified solvents, and then calcined at 450 \u00b0C overnight. After all, as mentioned in this review, it is expected that miniaturized and automated extraction techniques and high-throughput analytical approaches will continue to be developed to improve the accuracy of PAEs determination."} +{"text": "Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high\u2010quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures \u2013 namely translational research, clinical/prevention trials and outcomes research \u2013 were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next\u2010generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health\u2010related quality\u2010of\u2010life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU\u2010wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost. Key stakeholders from the cancer research continuum met at the European Cancer Research Summit to discuss priorities for the successful implementation of Cancer Mission and Europe's Beating Cancer Plan. The resulting Porto Declaration called for a collective action to develop cancer research infrastructures, foster innovation and decrease inequalities. Here, we present the Summit recommendations for an EU\u2010wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of cancer patients and survivors. AIartificial intelligenceBECASpecial Committee on Beating Cancer of the European ParliamentBoBBasket of Baskets CCCComprehensive Cancer CentreCCECancer Core EuropeCEEAOCentral\u2013Eastern European Academy of OncologyDARTData Rich Clinical TrialsDKFZGerman Cancer Research CenterDKTKGerman Cancer ConsortiumDRUPDrug Rediscovery ProtocolEACSEuropean Academy of Cancer SciencesEBCPEurope\u00b4s Beating Cancer PlanECACEuropean Code Against CancerECPCEuropean Cancer Patient CoalitionEFPIAEuropean Federation of Pharmaceutical Industries and AssociationsEMBLEuropean Molecular Biology LaboratoryEORTCEuropean Organisation for Research and Treatment of CancerERNEuropean Reference NetworkESMOEuropean Society of Medical OncologyIARCInternational Agency for Research on CancerIMIInnovative Medicine InitiativeIQNPath International Quality Network for PathologyJRCJoint Research Centre EUMRImagnetic resonance imagingMTBMolecular Tumour BoardNCTNational Center for Tumor DiseasesNGSnext\u2010generation sequencingOECIOrganisation of European Cancer InstitutesQoLhealth\u2010related quality of lifeRCTrandomized clinical trialRTradiation therapyVBHCvalue\u2010based health careWGSwhole\u2010genome sequencingWSIwhole\u2010slide images1The effective implementation of the EU cancer research strategy has been the focus of the European Cancer Research Summit, which took place in Porto in May 2021 and mainly discussed the requirements for distributed and interconnected infrastructures needed to support research on cancer therapeutics, care and prevention . This inAs an integral part of the Horizon Europe Framework Programme for Research and Innovation (2021\u20102027), a set of European Research and Innovation Missions aim to deliver solutions to some of the greatest challenges facing Europe, including cancer. As highlighted by one of the Summit speakers, Guy van den Eede, cancer accounts for more deaths than any other disease in the age group of below 65 in the EU. While this geographical area is home to <\u00a010% of the world\u2019s population, it collects 23% of all cancer cases. On average, only one in two cancer patients survive, and one in two of us will face cancer in our lifetimes. In economic terms, cancer costs the EU almost \u20ac97 billion in 2018. In futuristic terms, several factors, including the EU\u2019s ageing population, will see that all numbers and costs increase unless serious action is taken, such as doing more on prevention, early detection, quality of care and more .In the context of Horizon Europe, both the Cancer Mission , 6, 7 anIn this landscape, policymakers, academic researchers, patient representatives and pharmaceutical industry members contributed to keynote sessions and panel discussions at the European Cancer Research Summit 2021. Rui Henrique, the main organizer, and Julio E.\u00a0Celis, the Chair of the Scientific Advisory Committee, welcomed the Summit participants. The Summit started with a brief glimpse over current developments in the European cancer policy landscape. It continued with distilling the view of the cancer research community on the basic requirements that will enable the implementation of an effective European Cancer Mission. Finally, it focused on the specific recommendations by key stakeholders to establish efficient infrastructures for translational research, clinical/prevention trials and outcomes research. Panel\u00a0discussions complemented the perspectives of key lectures and set the scene for a multivoiced, yet highly collaborative, pan\u2010European initiative to tackle the challenges of cancer for the individual, the health systems and the society.2Stella Kyriakides, opened the session by thanking the cancer community for supporting EBCP, which in partnership with the European Cancer Mission will address current challenges in cancer research, prevention and care. Ms\u00a0Kyriakides highlighted the importance of interdisciplinary collaboration and emphasized the need for evidence\u2010based knowledge and its translation into policy and political decisions. The planned EU initiatives for fostering cancer research, prevention and care will financially be supported partly by EU4Health, but, as Ms Kyriakides noted, the clear commitment of all EU member states would be equally crucial. In addition, European Comprehensive Cancer Centres (CCCs) and the European Parliament Special Committee on Beating Cancer (BECA) will have key parts in these efforts \u2013 the concrete contribution of BECA being currently under discussion.The Summit\u00b4s first session focused on current and future European cancer policy plans, in which collaboration among policymakers, scientists and patient organizations is deemed indispensable. The EU Commissioner for Health and Food Safety, Marta Temido, Minister for Health, Portugal, recognized that public health authorities alone could not tackle the major societal challenge of cancer. Ms Temido highlighted the need to invest in research and technology using a research\u2010driven, patient\u2010centred approach and mentioned that BECA would support efforts across the EU. While clinical research and the national cancer plan are key priorities of the Portuguese government, they should also be prioritized by all other EU member states, indicated Ms Temido, who also encouraged EU member states to sign the \u2018Porto Declaration\u2019.Further corroborating the message of Stella Kyriakides on the importance of collaboration, Mariya Gabriel, EU Commissioner for Innovation, Research, Culture, Education & Youth, next informed the audience that the health cluster of Horizon Europe features a Cancer Mission with well\u2010defined goals as a key priority, aiming at improving prevention, diagnosis and treatment. While the COVID\u201019 pandemic caused delays in cancer research and weakened European Research Networks (ERNs), Horizon Europe is expected to restrengthen partnerships in health, such as the partnership on personalized medicine, innovative health initiatives that build on the success of the Innovative Medicine Initiative (IMI), and the European Institute of Innovation and Technology Health. According to the Commissioner, work on the Cancer Mission implementation plan is currently underway; the next is to invigorate EU member states and regional funders. Marie Sklodowska\u2010Curie actions will also help build scientific excellence and cooperation across countries. The new EC Knowledge Centre on Cancer, launched on 30 June 2021, is expected to coordinate the efforts of EU member states and similar IP portfolios. MB confirms that, to the best of his knowledge, none of the above funding sources were involved in the preparation of this paper. BB has received research funding from 4D Pharma, Abbvie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi\u2010Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche\u2010Genentech, Sanofi, Takeda, Tolero Pharmaceuticals. FC declares consultancy role for: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi\u2010Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck\u2010Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre\u2010Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva. SF is a consulting or advisory board member at Bayer, Illumina, Roche; has received honoraria from Amgen, Eli Lilly, PharmaMar, Roche; has received research funding from AstraZeneca, Pfizer, PharmaMar, Roche; has received sponsorship of travel or accommodation expenses by Amgen, Eli Lilly, Illumina, PharmaMar, Roche. SG owns AstraZeneca stock and is a full\u2010time employee of AstraZeneca. PN has had an advisory role at Bayer, MSD Oncology, has received honoraria from Bayer, Novartis and MSD Oncology, and has had travel expenses paid by Novartis. JO has been an advisory board member at Roche, Novartis, Bayer, Merck, Eisai, Astrazeneca, Pierre Fabre Medicament and Bristol\u2010Myers Squibb. He has also received research funding by IPO Porto, Astrazeneca, Funda\u00e7\u00e3o para a Ciencia e a Tecnologia (FCT) and Liga Portuguesa Contra o Cancro (LPCC). AR is an employee of European Federation of Pharmaceutical Industries and Associations, Brussels, MSD International Business GmbH, Kriens, Switzerland[CvG1], and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA, who may own stock and/or hold stock options in the Company.RS serves as principal investigator of the ASCO TAPUR study. ASCO receives research grants from the following companies in support of the study: Astra\u2010Zeneca, Bayer, Boehringer\u2010Ingelheim, Bristol Myers Squibb, Genentech, Lilly, Merck, Pfizer, Seattle Genetics. Dr. Schilsky serves as a member of the managing board of Clariifi and as a consultant to Bryologyx, Cellworks Group, EQRx, and Scandion Oncology. The Netherlands Cancer Institute receives research support via EV from Roche, Astrazeneca, Eisai, Novartis, GSK, Clovis, BMS, MSD, Pfizer, Amgen, Bayer, Lilly, Janssen and Seagen. LZ is founder of everImmune, member of the board of directors of Transgene, member of the scientific advisory board of Transgene, EpiVax, Lytix Biopharma. LZ has also had research contracts with: Merus, Roche, Tusk, Kaleido, GSK, BMS, Incyte, Pileje, Innovate Pharma, and Transgene and has received honoraria by Transgene. All other authors have no conflicts of interest to declare."} +{"text": "Fertilization can significantly affect the quality of crop and soil. To determine the effects of long-term fertilization on crop yield and carbon:nitrogen:phosphorus (C:N:P) stoichiometry in soil, a study was conducted on the terraced fields of the Loess Plateau from 2007 to 2019. Nine fertilization treatments were included: no fertilizer; organic fertilizer (O); organic and nitrogen fertilizers (ON); organic, nitrogen, and phosphorus fertilizers (ONP); organic and phosphorus fertilizers (OP); phosphorus and nitrogen fertilizers; potash and nitrogen fertilizers; potash, nitrogen, and phosphorus fertilizers; and potash and phosphorus fertilizers. Under these treatments except for CK and PK, crop yields initially decreased but later increased. The nutrient content and C:N:P stoichiometry increased in soil depth of 0\u201320 cm. The soil available nutrients did not change significantly with the duration of fertilization. The O, ON, ONP, and OP had the most evident effect on the enhancement of soil nutrient content, whereas O and ON had the most evident effect on the increase in soil organic carbon (SOC):total phosphorus (TP) and total nitrogen (TN):TP. In soil depth of 0\u201320 cm, crop yield, SOC:TN, SOC:TN, SOC:TP, and TN:TP significantly correlated with soil nutrients. This study indicated that long-term fertilization can effectively improve crop yield, soil fertility, and soil C:N:P stoichiometry. Meanwhile, the single application of an organic fertilizer or the combination of organic and nitrogen fertilizers can improve the condition of nitrogen limitation in arid and semi-arid areas. Ecological stoichiometry is the science of studying the energy balance of biological systems and multiple nutrient elements , nitrogen (N), and phosphorus (P)) . It provIn agricultural production practices, fertilizers (organic and inorganic) are used to increase the accumulation of C, N, and P in the soil to improve the soil\u2019s ability to supply nutrients to crops . FertiliFertilization is one of the most important methods in agricultural production. Studies have found that soil nutrients and crop growth are affected by frequent fertilization and other factors ,11. FertIn the present study, we chose a typical terraced field plot in the Loess Plateau to conduct a 12-year experiment (from 2007 to 2019) on various fertilization treatments. The objective was to study the changes in characteristics of crop yield, soil nutrient content, and C:N:P stoichiometry with various fertilization methods under different fertilization durations. We hypothesized that (1) long-term fertilization may affect the crop yield and soil nutrient content, (2) the changes in soil nutrient content may alleviate the C:N:P stoichiometry of soil, and (3) the single application of an organic fertilizer or an organic fertilizer combined with an inorganic fertilizer may have an advantage in increasing crop yield and soil nutrients supply.The study site was located at the Ansai Research Station of the Chinese Academy of Sciences , which is a long-term detection sampling site . The ann2 was selected and divided into 36 small plots of 3.5 m \u00d7 8.57 m. In total, 9 fertilizer treatments were performed, and each treatment was repeated 4 times software.Effects of the type of fertilization treatment and duration of fertilization on crop yield, SOC, TN, TP, AN, AP, pH, SOC:TN, SOC:TP, TN:TP, and AN:AP were evaluated using two-way ANOVA. One-way ANOVA was used to evaluate the crop yield, SOC, TN, TP, AN, AP, pH, SOC:TN, SOC:TP, TN:TP, and AN:AP responses to the duration of fertilization. Duncan\u2019s post hoc test at The type of fertilization treatment and duration of fertilization had a considerable impact on crop yield . BetweenAt 0\u201320 cm soil depths, the duration of fertilization had a significant impact on SOC, TN, TP, AP, and pH . BetweenIn soil depths of 20\u201340 cm, the duration of fertilization had a significant impact on SOC, TN, TP, AN, AP, and pH . BetweenIn soil depths of 0\u201320 cm, the duration of fertilization had a significant impact on SOC:TN, SOC:TP, TN:TP, and AN:AP . BetweenIn soil depths of 20\u201340 cm, the duration of fertilization had a significant impact on SOC:TN, SOC:TP, TN:TP, and AN:AP . BetweenFor the soil depth of 0\u201320 cm, the correlation matrix showed that crop yield was significantly correlated with SOC, TN, TP, AN, AP, pH, and SOC:TN; SOC:TN with SOC, TN, AN, AP, pH, SOC:TP, and TN:TP; SOC:TP with SOC, TN, TP, AN, AP, TN:TP, and AN:AP; and TN:TP with SOC, TN, TP, AN, AP, pH, and AN:AP a.For the soil depth of 20\u201340 cm, the correlation matrix showed that crop yield was significantly correlated with SOC and TP; SOC:TN with SOC, TN, AN, AP, pH, and SOC:TP; SOC:TP with SOC, TN, TP, and TN:TP; and TN:TP with SOC, TN, TP, AN, pH, and AN:AP b.Increasing crop production is one of the ways to increase agricultural development in arid and semi-arid regions. Fertilization is an important agronomic measure, and appropriate application of fertilizers can promote the growth and development of farming and improve the quality and yield of crops ,21. ThisThis result can be explained as follows. First, N, P, and potassium (K) are essential nutrients for the growth and development of crops. During the long-term growth of crops, the nutrient elements in the soil are consumed in large quantities. The addition of artificial fertilizers compensates for the deficiency of soil nutrients, thereby increasing the absorption and assimilation of soil N, P, and K by plants; this affects the growth and development of crops, further affecting crop yield . Second,Studies have reported that organic fertilizer is released slowly, and it cannot meet the growth needs of crops in the current season. However, the fertilizer effect is long ,23. ThisSoil nutrients can provide the material basis and energy source for the survival of various microorganisms in the soil and the growth of crops . Soil nuA lack of fertilization long term leads to an increase in the soil nutrient content in the soil layer of 0\u201320 cm, which is inconsistent with the conclusion that a lack of fertilization long term leads to a decrease in soil organic matter content . It may At a soil depth of 0\u201320 cm, the application of organic fertilizer or mixed application of organic and inorganic fertilizers had a more enhanced effect on soil nutrient content than the single application of inorganic fertilizer . This isIn this study, it was found that the SOC:TN in 0\u201320 cm soil layer increased after fertilization with the increase in the number of years of fertilization. Studies have found that the main factors affecting the changes in SOC:TN are changes in SOC and soil TN content after fertilization ,31. SOC:SOC:TP in soil can characterize the potential of soil organic matter mineralization to release or absorb and fix P ,32. AddiIn addition, we found that the overall rate of increase in TN was greater than that in TP under O and ON treatments , resultiIn conclusion, we studied nine fertilization treatments for millet in arid and semi-arid areas and found that crop yield and C:N:P stoichiometric ratio in soil were significantly affected by the duration of fertilization. The long-term use of organic fertilizer, inorganic fertilizer, or a combination of both can effectively increase crop yield, improve soil nutrient environmental conditions, and improve C:N:P stoichiometry in 0\u201320 cm deep soil layer. The effect of organic fertilizer and combined application of organic and inorganic fertilizers on increasing soil nutrient content is more evident. Fertilization using organic fertilizer or organic fertilizer combined with nitrogen fertilizer can effectively alleviate nitrogen limitation in arid and semi-arid areas. Therefore, this study provided supportive data for changes in soil nutrient content and C:N:P stoichiometric ratio after long-term fertilization in arid and semi-arid regions and provided a theoretical basis for efficient soil fertilization in such areas."} +{"text": "Background: Over the last decades, life expectancy in Latin America and the Caribbean showed a rapid increase, which led to a significant increase in the number of people with dementia. Moreover, 9% of the population in this part of the world are aged 65 or older, and by 2050 this percentage is projected to at least double. For this reason, it is essential to estimate the prevalence of dementia in LAC countries with the aim to determine suitable actions to enhance the quality of life of those affected. Methods: Database searches for articles were conducted September 2020 throughout Pubmed, Web of knowledge, Scopus, Lilacs, and SciELO. The inclusion criteria comprised population- or community-based studies, published in English, Spanish, or Portuguese, reporting data on the prevalence of dementia collected in LAC countries. The complete data search retrieved 1719 non-duplicates. Results: A total of 58 studies met the high-quality inclusion criteria, published 1991-2020, including participants in the following countries: Brazil, Mexico, Argentina, Colombia, Peru, Cuba, Dominican Republic, Venezuela, Ecuador, Trinidad and Tobago, and Jamaica. The most common form of dementia studied was Alzheimer\u2019s disease with prevalence ranging from 5.9% to 23.4%. Estimates differed by age, gender, and education, with oldest, women, and lower-educated adults living in rural areas presenting higher dementia prevalence. Conclusion: This is the first study giving a comprehensive overview of dementia prevalence in LAC countries, which is relevant to estimate care needs and economic costs related to dementia treatment and care."} +{"text": "In \u201cCensus Tract Patterns and Contextual Social Determinants of Health Associated With COVID-19 in a Hispanic Population From South Texas: A Spatiotemporal Perspective\u201d :e29205), one error was noted.Due to a system error, the name of one author, Joseph McCormick, was replaced with the name of another author on the paper, Isela de la Cerda. In the originally published paper, the order of authors was listed as follows:Cici Bauer, Kehe Zhang, Miryoung Lee, Susan Fisher-Hoch, Esmeralda Guajardo, Isela de la Cerda, Isela de la Cerda, Maria E Fernandez, Belinda ReiningerThis has been corrected to:Cici Bauer, Kehe Zhang, Miryoung Lee, Susan Fisher-Hoch, Esmeralda Guajardo, Joseph McCormick, Isela de la Cerda, Maria E Fernandez, Belinda ReiningerIn the originally published paper, the ORCID of author Isela de la Cerda was incorrectly published as follows:0000-0002-5844-8102This has been corrected to:0000-0003-3625-8954The correction will appear in the online version of the paper on the JMIR Publications website on August 18, 2021, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "GPs are increasingly confronted with patients with both intellectual disabilities (ID) and mental health disorders (MHD). Currently, the care provided to these patients is found to be insufficient, putting them at risk of developing more severe MHD. Improving the quality of GP care will improve the whole of mental health care for this patient group. Therefore, an overview of the content and quality of care provided to them by the GP may be helpful.To provide an up-to-date literature overview of the care provided by GPs to patients with ID and MHD, identify knowledge gaps, and inform research, practice, and policy about opportunities to improve care.Scoping review.PubMed, PsycINFO, EMBASE, and grey literature were searched for publications concerning primary care and patients with ID and MHD. Selected publications were analysed qualitatively.One hundred publications met the inclusion criteria. Five overarching themes were identified: GP roles, knowledge and experience, caregiver roles, collaboration, and a standardised approach. The results show GPs\u2019 vital, diverse, and demanding roles in caring for patients with both ID and MHD. GPs experience problems in fulfilling their roles, and gaps are identified regarding effective GP training programmes, applicable guidelines and tools, optimal collaborative mental health care, and corresponding payment models.The improvement required in the current quality of GP care to patients with ID and MHD can be achieved by bridging the identified gaps and initiating close collaborations between care professionals, policymakers, and organisational managers. Their care provision constitutes both a demand-driven approach in assessment, treatment, and follow-up of symptoms and disorders, and a more proactive approach aimed at prevention by identifying risk factors and providing health education. Adequate primary care, including both of these approaches, is essential for patients with both ID and MHD to prevent diagnostic delay and ensure appropriate and timely referral and early personalised treatment.16,17 reported practices are mostly on a small scale and lack an orientation towards primary care. This is surprising and disturbing, considering GPs\u2019 important position in the mental healthcare system and the growing demands of this patient group.Although studies are increasingly published on expanding knowledge and skills within mental health care and ID care,A scoping review was conducted to enhance the level of knowledge and provide an up-to-date overview of GP care for patients with both ID and MHD, identify knowledge gaps, and inform research, practice, and policy about opportunities to improve care.18 framework for scoping reviews, revised by Khalil et al,19 and describes methods and results in line with the PRISMA Extension for Scoping Reviews checklist.20This review follows Arksey and O\u2019Malley\u2019sThe guiding research question was: what has been described about the care for adult patients with both ID and MHD provided by GPs? The key concepts are defined in Supplementary Table S1.19 First, PubMed, PsycINFO, and EMBASE were explored (date range from January 1994 to September 2019), using search terms pertaining to \u2018primary care\u2019 and \u2018intellectual disability\u2019, informed by an information specialist (Supplementary Table S1). Selected publications were searched for keywords missed in the initial search. This yielded an additional search string for \u2018ID\u2019 (Supplementary Table S1). Second, relevant publications were retrieved from grey literature, using the recommendations from \u2018Grey Matters\u2019.21 Common search terms for \u2018primary care\u2019 and \u2018intellectual disability\u2019 in English and in Dutch were used (Supplementary Table S1). Third, the reference lists were searched for additional relevant publications.Relevant publications were identified using a three-step literature search.adult focused (\u226518 years);originating in Western European and Anglo-Saxon countries, where GPs have a comparable role as gatekeeper for more specialised mental health care;available in full text; andavailable in English or Dutch.Duplicates were removed, and the first author performed a first selection on title and abstract. About 20% were double screened by a second independent researcher. The full texts were then screened by the first author and a second independent researcher. Any judgement differences were discussed to reach consensus within each review pair. When consensus could not be reached, a third reviewer became involved to resolve outstanding conflicts. Publications were included if they concerned adults with an ID, an MHD, and primary care following the prepared definitions. Other criteria were:There was no selection on publication type. Publications on forensic primary care were excluded because they concern a selective group of patients beyond the scope of this review.22 supported by ATLAS.ti software (version 8.4). This process involved repeatedly reading the articles, identifying relevant text fragments, and inductively generating codes related to the research question. All coding was conducted by two researchers independently. Differences in coding were discussed to reach consensus. Codes were then sorted depending on how they were related. From this, major themes were developed and organised. This iterative process was followed critically by the research team, and key findings were discussed relating to the study\u2019s purpose and implications for future research, practice, and policy.A standardised data extraction form was developed to guide data charting for descriptive analysis, including publication year, country of origin, publication type, domain, and the care element(s) described. The selected publications\u2019 content was qualitatively analysed using conventional content analysisn = 39) and primary care (n = 34). The number of yield publications increases steadily over the years. In total, 46 of the publications described a scientific study, none of which were randomised controlled trials. 23\u201326 Primary care databases show a prevalence of MHDs in adult patients with ID ranging from 21%\u201334%.4,23,25\u201327 GPs\u2019 screening of patients with ID or MHD identified 33%\u201371% of patients as having a possible MHD and needing further medical assessment.28\u201331 Severe mental illnesses such as schizophrenia, bipolar disorder, and psychosis are more prevalent in patients with ID.3,4,23,32,33 Depression and anxiety are recorded less,33,34 equally,4,34 or more often,23 with an earlier age of onset for depression.35 Smoking, alcohol, and other substance use are less prevalent,23,33 but alcohol misuse is more prevalent in patients with ID.23The publications on register-based cohort studies report that people with ID have a higher risk of MHDs than patients without ID.Thematic analysis revealed five overarching themes: GP roles, knowledge and experience, caregiver roles, collaboration, and a standardised approach. The results are narratively presented accordingly. 31,36\u201345 Several GP roles in the care for this patient group are described, however, with varying acceptance, experience, and fulfilment among GPs.42,46,47The publications reveal the GP as the key figure in the identification, initiation, and coordination of treatment of patients with ID and MHD.32,43,44,48,49 in the sense of a \u2018proactive approach\u2019. This comprises general health promotion and targeted education about healthy living or substance use,32,44,49 but also identification of MHD-provoking risk factors and development of prevention strategies.31,43,48,49The GP roles relate, in the first place, to \u2018prevention of MHDs\u2019,diagnostic assessment of MHDs, which is described as challenging for GPs.50 Indications of inaccurate diagnoses48,51 and underdiagnosis in primary care are frequently reported4,31,41,42,48,49,52\u201356 and may result in inappropriate care and progression of the disorder to a more severe stage that is less responsive to treatment.23,52,57\u201359 Overdiagnosis occurs as well, however, leading to unnecessary prescriptions of medication.53,57 Diagnostic failure is seen as related to communication problems, with patients with ID described as less able to label their feelings and communicate their needs,44,53,57,60\u201362 resulting in an atypical presentation of symptoms29,43,44,57,63\u201365 and a more complicated assessment.42,48,52,54,61,66 It is deemed important for the GP to exclude somatic, environmental, and other causes of symptoms before considering an MHD,43,44,48,51,53,64,65,67\u201373 which requires a holistic, multidimensional approach.29,44Second, GPs are expected to fulfil an important role in the 40,44,68 For this patient group the same requirements and treatment guidelines apply as for patients with MHD but without ID,44,57,65,71,73 with the necessity to refer patients with more complex disorders to specialised care.44,68 GPs prescribe psychotropic medication to a higher number of patients with ID (17%\u2013 63%) than other patients.4,74,75 In addition, a higher number of patients with ID are reported with psychotropic prescriptions than with recorded MHDs, indicating off-label prescription.4,39,44,49,75\u201380 Behavioural problems are often described as an indication to start medication,4,39,59,73,74,78,79 specifically in cases of limited access to alternative treatment strategies.4 Prescribed medication is reported as predominantly long-term medication,75 and a large proportion (62%\u201370%) is prescribed without a psychiatrist\u2019s involvement.50,51,81 Medication prescription can be considered part of a multidisciplinary and holistic care plan;65 however, in primary practice, GPs are less likely than psychiatrists to provide psychosocial interventions.72Third, regarding GPs\u2019 \u2018treatment role\u2019, it is indicated that GPs should be able to handle less complex MHDs in people with ID.48,50,65,69,73,82\u201384 It enables the monitoring of treatment responses and possible adverse side effects, leading to early adjustment of the treatment plan.50,73 However, a lack of effective monitoring of psychotropic medication by GPs is often described.28,42,51,55,74,81,85,86 It is stipulated that this relates to GPs\u2019 lack of specific experience and knowledge,51,81,87 uncertainty about who of the involved professionals is responsible for follow-up,47,83,86,88,89 patient problems in communicating and presenting (side) effects of medication,44,49,65 and dependence on observations by, and cooperation with, caregivers.39,44,49,50,62,69,72Finally, \u2018follow up\u2019 by GPs is considered an essential element in the treatment of patients with ID and MHD.24,37,40,42,43,46,50\u201352,58,66,69,81,87,90\u201396 caused by a lack of priority in medical training programmes37,40,43,50,52,58,66,93 and a lack of research concerning this patient group.93 This results in limited evidence-based knowledge43,47,50,65,67,93,97 and reliance on experience-based knowledge instead.50 It is indicated that limited knowledge and experience create feelings of insecurity in GPs when addressing patients with ID and MHD,50 lack of caregivers\u2019 confidence in the GP,52 and insufficient care.37,41,44,52,58,66,81,91,92,97 Although GPs are interested in more training and education regarding patients with ID and MHD,24,37,41,42,44,52,58,66,87,90,91 in practice it is seen as a challenge to engage them, caused by the small size of the population and the variety of competing medical issues.58,70 Publications underline the importance of investment in more research and initiatives for effective training, skill development,37,42,50,58,92,96 and evidence-based guidelines for GPs.42,50,98There is general consensus that GPs generally have limited knowledge about, and experience in, managing patients with ID and MHD,23,43,49,57,62,69,72,99 as a first point of reference, to recognise symptoms of MHDs and seek help.23,43,62,73,99 For this task, it is deemed important that caregivers have some knowledge of associated symptoms; however, this knowledge is often lacking.23,42\u201344,100 Second, patients are frequently dependent on caregivers for joint decision making44 and giving informed consent regarding treatment options such as psychotropic medication.4,49,65,68,72 Third, caregivers have important roles in the execution of the treatment plan regarding medication adherence and identifying and monitoring possible side effects.49,50,73,82 A symptoms checklist is mentioned as a helpful tool for caregivers to provide the GP with the information needed.40,73 Furthermore, it is noted that the referral process can be complex, and support by caregivers can be essential to prevent delay in care.96,100In the publications, it is noted that patients with ID and MHDs are often reliant on formal or informal caregivers for receiving care,29,43,44,53,57,60\u201365 overcoming communication difficulties,43,57,69,72 and providing additional information.57,63,73 It is indicated that the more severe the ID, the more reliant the GP is on caregivers.63 Therefore, GPs should determine the key people in a patient\u2019s life73 and proactively involve them.49,72 However, GPs should also realise that some caregivers may give information from their personal perspective, use different definitions of medical terms than the GP,44 and themselves have limited knowledge about the patient53,62,72,81,94 or limited communication skills.42,44In addition, the GP is reliant on caregivers understanding symptom presentation,43,44,49,50,56,63,64,72,75 level of communicational skills and cognitive functioning,44,86 and obtaining advice on referral,31,72,78 treatment,30,44,48\u201350,72,75,86 or prevention.49 GPs\u2019 options include referral for collegial advice,31,48,72,94 handing the patient over to other professionals,44 or joining a multidisciplinary team giving integrative care to the patient.93,98,101 The latter is described as particularly desirable when the patient has a more severe ID or is in a highly complex situation.39,44,99The publications emphasise the importance of GPs collaborating with other professionals in providing care for patients with ID and MHD. The collaborative partners mentioned are diverse and comprise both medical specialists and services such as community or addiction services. Described areas for collaboration are the assessment of symptoms,28,39,42,44,93,94,96,98,102 as it is believed to increase the identification of MHDs, improve access to mental health care,98,101 and reduce hospitalisation103 and costs.98,101 However, inappropriate referrals are reported,90,94 resulting from unclear referral options and procedures.44,45,96,100,104 Adequate information exchange between GPs and other professionals, in the form of standardised, timely letters, is underlined as important for sharing essential information38,62,94,105\u2013107 and continuity of care.105,106 Yet, audit studies on referral letters and letters from psychiatrists to GPs show that important information is often missing.62,94,100,105,107 Finally, it is stated that, in multidisciplinary collaboration, the alignment of responsibilities in treatment and follow-up should be clear.44,68,108 Particularly in cross-domain collaboration, it may be unclear who is involved, how responsibilities are shared, and how care is financed.47,83,86,88,89,96,104 It is mentioned that adequate division of responsibilities may depend on the main causal factor(s) of the MHD and may necessitate using care plans and convening case conferences.68 Responsibilities should be clearly stated in writing and reviewed regularly.88 Consequently, suggested preconditions for effective collaboration are accessible referral options, clarity about referral procedures, adequate information exchange between the professionals, and consensus on responsibilities.3,24,39,41,88,94,96,107Effective collaboration is seen as beneficial for the outcome of mental health care in primary care98 organisationally,42 and financially.96,98,101 To improve the quality of collaboration, the roles of both GPs and other involved professionals should be defined more clearly,60,72 existing models should be evaluated,42,109 clinical pathways and/or models should be improved,24,42,109 specialist capacity should be enhanced,41 and payment models should be re-examined to stimulate collaborative care.98,101 Policymakers\u2019 involvement in this matter is seen as important.98,101It is noted as a barrier that, from a historical point of view, primary and secondary care services are separate units culturally,43\u201345,49,50,65,68,83,110 First, standardised screening for MHDs gives GPs the opportunity to consider potential mental health issues at an early stage.44,49 Second, a structured multidimensional approach in the assessment leads to more appropriate and accurate diagnosis, treatment, and referral.44,45,49,65,68 Finally, systematic and standardised medication prescriptions and reviews identify potential medication-related problems at an early stage.43,50,65,83,110In several publications, a standardised approach is seen as a way to improve the quality of care for patients with both ID and MHD.40,43,44,72,73,80 Some publications covered specific guidelines for prescribing and/or monitoring medication for MHDs in patients with ID,39,47,49,54,59,65,67,73,82 and applicable tools for detecting unmet health needs in patients with ID.31,40,49,60,69 It is suggested that GPs are insufficiently familiar with these ID-specific guidelines and tools.51,87Although guidelines and instruments are available to support GPs in applying a standardised approach in the general population, they are often not adapted to patients with ID.To the authors\u2019 knowledge, this is the first scoping review with a focus on patients with both ID and MHD in primary health care. GPs are a key figure in the care for this specific patient group. They have a broad role that can be demanding in the sense that GPs need specific knowledge, experience, and skills for a relatively small patient group. The publications indicate that current GP care is often of an insufficient standard, as reflected in underdiagnosis of MHDs, overmedication, and lack of effective patient follow-up. Gaps are identified regarding effective training programmes for GPs, applicable guidelines and tools, optimal collaborative mental health care, and corresponding payment models. Opportunities for improvement are seen in prioritising and investing in bridging these gaps. This requires the involvement not only of care professionals and scientists, but also of policymakers.19 was used to provide a solid overview of the existing knowledge on GP care for patients with both ID and MHD. Second, only publications from countries where GPs have a gatekeeper role were included. This results in recommendations that can improve not only the quality of GP care, but also the overall mental health care for patients with ID. Finally, to prevent dispersion of the results of an already broad research question, this study focused on adults, thereby giving attention to a vulnerable group that is potentially more overlooked than children.The first strength of this review is that a robust and widely accepted scoping review method21 and checking references lists. Some publications were not accessible for the research team, and publications could have been missed because of the great diversity of possible sources.This review also has limitations. First, a lack of consistency was found in the definition of ID, as many publications did not supply a clear definition of it. This limitation reflects the heterogeneity of the patient group, and results should be interpreted accordingly. Second, the publications retrieved in the grey literature search are presumably not perfectly complete, despite the use of the \u2018Grey Matters\u2019 tool58,70 However, this claim regarding the proportion of patients is debatable. In the Netherlands, it is estimated that 6.4% of the population have a mild ID.1 Research in primary care data shows that no more than 0.56% of GPs\u2019 clients are registered as having an ID.23,34 This could be an indication of GPs\u2019 insufficient recognition and underestimation of the size of the ID population. This underestimation is also present in mental health care and is a reason for concern.7 Identification of an ID is essential both for good care provision and for treatment success in MHDs.14 Helpful ID screening tools have been developed for GPs when they are considering an ID, but further implementation in practice is needed.111,112The results of this review indicate that patients with ID constitute a small group within the GP population, accounting for the low priority of this group in education and research.12,113 It is also suggested that GPs should use the same treatment guidelines for mild or less complex MHDs in patients either with or without ID.44,57,65,71,73 However, research to substantiate this is scarce, and research in addiction care shows that alterations in the treatment programmes for substance use disorders are needed for patients with ID.10 Furthermore, previous research projects have led to practical primary care tools, such as the Psychiatric Assessment Schedule for Adults with Developmental Disabilities (PAS-ADD).31,60 However, these tools are not fully implemented in primary care.The results from this study revealed two strategies to improve care for patients with both ID and MHD: adequate medical training and applicable evidence-based guidelines and tools. This is in line with previous reports and publications concerning general health issues in patients with ID.114 This review had an international focus, and the possibilities of multidisciplinary approaches in primary care differ in the various healthcare systems. Within the ambitions and possibilities of the NHS, the UK sees integrated care systems as an important tool for improving health care and for reducing inequalities between different groups of people,115 and has long-term experience with community learning disability teams. These multidisciplinary teams provide health care and advice to people with ID, GPs, carers, families, and to the wider health and social care community.116 Another example of promising collaboration in daily practice is \u2018The DD Health Home\u2019 in the US. This care model provides integrative routine care to patients with ID and MHD, including primary care and structural follow-up.98 Despite these best practices, there is at present limited scientific evidence on the effectiveness of these collaborative healthcare services for persons with ID.117 Preconditions for collaborative care, as listed in 118\u2013120 All these disciplines mention adequate reimbursement as a critical barrier to successful collaboration, and reimbursement needs to be prioritised. Additionally, collaboration is more effective when there is a team vision, shared goals, formal quality processes, and shared ICT information systems.118,120 Research in older person care has revealed that GPs are indispensable in multidisciplinary teams regarding networking activities, integration of care, and showing leadership; the researchers stress that GPs should be made more aware of this, for instance, in GP training programmes.121This review identified various kinds of primary care collaborations in which GPs participate, and shows that effective collaboration can improve care; the latter is widely supported and confirmed by the World Health Organization.13,122,123 The UK National Institute for Health and Care Excellence guideline Mental Health Problems In People With Learning Disabilities: Prevention, Assessment And Management gives special attention to the involvement of people with ID and their caregivers in organising their care. In addition, this guideline covers mental healthcare in a holistic way in different UK settings, and may serve as an example for other countries.124Finally, the results of this review stress the importance of the GP collaborating with caregivers. Remarkably, none of the included publications focused on patients\u2019 needs in their contact with the GP, although research shows that people with ID prefer to be less reliant on caregivers in GP consultation and argue for an improvement of the accessibility of health services.Improvement of care for patients with both ID and MHD needs to be prioritised, justified by the limited quality of care and the substantial size of this patient group. This improvement cannot be achieved by GPs and their collaborative partners alone. It requires adaptations on both the organisational and the political level. However, it remains important to actively engage GPs to ensure that suggested strategies are applicable and feasible in daily practice.Diverse improvement strategies are advisable. First, it is important to invest in effective, frequently recurring post-curriculum training programmes for GPs, focusing on more awareness of this patient group, specific knowledge gaps regarding IDs and MHDs, existing tools and guidelines, and GP roles in multidisciplinary teams. Offering training programmes in an interprofessional setting can support the latter and will additionally promote collaboration between care professionals. Second, ongoing policy changes, such as the move to integrated care systems in the UK, and best practices such as the community learning disability teams in the UK, provide opportunities for further development of optimal collaborative healthcare models for patients with both ID and MHD. Policymakers should re-examine payment models to create incentives for collaborative care, facilitate shared ICT information facilities, and involve potential users in the development of these healthcare models. Third, although the increase in publication over the recent years is a positive sign, more research is still needed on the effectiveness of existing general mental health guidelines and tools to determine whether they are truly applicable to patients with ID or whether specific alterations are needed. Priority should be given to guidelines and tools on MHD assessment, the prescription of psychotropic medication, and patient follow-up. Finally, further research should focus on the needs of caregivers in supporting patients, as well as on the needs of patients with both ID and MHD and how they can enhance their autonomy in GP contacts.This scoping review illustrates GPs\u2019 vital roles in the care of patients with both ID and MHD. Current GP care has generally proved insufficient, and improvement strategies are needed in close collaboration with policymakers and organisational managers. Multidisciplinary approaches in primary care \u2014 like those in the UK and US \u2014 seem promising, but still lack sufficient scientific evaluation. Investment in education, evidence-based guidelines and tools, and collaborative healthcare models is essential. This, supplemented with enhanced ID identification and attention to the needs of patients and their caregivers, may significantly improve the quality of care for this vulnerable patient group."} +{"text": "Figure\u00a06 as published. Figure\u00a06 was misplaced and needs to be corrected. The corrected In the original article, there was a mistake in 1, 2. Instead of \u201cIn the published article, there was an error in affiliation 1Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People\u2019s Hospital, Guangzhou Medical University, Guangzhou, China2Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China\u201d,it should be \u201c1Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China2Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People\u2019s Hospital, Guangzhou Medical University, Guangzhou, China\u201d.s for Weide Zhong. As well as having affiliation(s) 1, 3, they should also have, 2.In the published article, there was an error regarding the affiliationThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "COVID-19 is the name of an infectious disease called Coronavurus 2019, one of the causes of respiratory failure; The disease was first identified in Wuhan, China, in December 2019, and then spread around the world and also creating the 2019-2020 coronavirus pandemic . Due to Creating emotional problems and mental disorders such as stress, anxiety, and fear is one of the inevitable consequences of this disease that can cause stress, depression, and even suicide. Given that students, as a critical element of the educational system, have a unique role in achieving the educational system, it is essential to pay attention to their mental, emotional and physical health ,7,8. Mos Despite the significant advancement of virtual learning globally, due to courses\u2019 practicality in the higher semesters of nursing students, virtual education can have adverse effects on how they learn. On the other hand, nursing internship students, due to their close interaction with the hospital are affected by various conditions such as: Fear of being a Coronavirus carrier and its transmission to the family, high job fatigue, reduced sleep quality, malnutrition, fear of death, lack of proper communication with the family, frustration, Violent Behavior, etc.Also, in some studies, students\u2019 anxiety and the COVID-19 pandemic were higher than the national norm ,14. So, It is also essential to consider new approaches to teach clinical skills. Due to the clinic\u2019s distance, hospital, and eye to eye contact with patients, nursing internship, students have practical skill gaps. Therefore, encouraging students to use educational multimedia, clinical databases may be effective . Finally"} +{"text": "For the formation of a proto-tissue, rather than a protocell, the use of reactant dynamics in a finite spatial region is considered. The framework is established on the basic concepts of replication, diversity, and heredity. Heredity, in the sense of the continuity of information and alike traits, is characterized by the number of equivalent patterns conferring viability against selection processes. In the case of structural parameters and the diffusion coefficient of ribonucleic acid, the formation time ranges between a few years to some decades, depending on the spatial dimension . As long as equivalent patterns exist, the configuration entropy of proto-tissues can be defined and used as a practical tool. Consequently, the maximal diversity and weak fluctuations, for which proto-tissues can develop, occur at the spatial dimension 2.5. The origin of life was a chemical event and life on Earth began some billions of years ago ,2 and, wThe present article considers a pathway for attaining elementary prebiotic processes from a non-equilibrium point of view . Life isReplication: Reactants interact to produce a compound Variation: Spatial patterns promoting adaptation.The following concepts are adopStatements (a) and (b) are connected to physical and chemical procedures, where compound systems .This work is conducted using mathematic and simulation tools; nevertheless, qualitative explanations are offered regularly. Analytic or computational models for environments and prebiotic processes are broadly mentioned and, in this sense, this approach must be considered as a partial contribution to the following complex problem: prebiotic organization and configuration. The substrate where the aggregate of protocells develops is a simple compound, but it is enough to substantiate the notions developed in this work. I emphasize, this work considers only a lineal analysis related to possible final structures (proto-tissues). Explicit solutions and time evolution towards final structures will be performed elsewhere.For simplicity and to maintain basic central ideas, a generic Schnakenberg reactionmination ). The k As part of the required metabolism, and for simplicity, waste is considered through the loss rate Moreover, the basic spatial solutions of the above equations are assumed as A boundary, a spatial (hyper-) cube, is assumed for mathematical convenience. As usual in reaction\u2013diffusion equations ,28,29,30Here, the wave vector tability ,28,29,30Finally, long-range spatial or temporal (memory) effects ,22,23,24At this stage, for the generation of structures, I assume the realization of the fundamental condition (see Equation (3)) as the following: systems .Equation (5) reveals that the rate of production of compound Finally, semi-analytical solutions of Schnakenberg\u2019s equation, including limit cycles, can be viewed in reference to Noufaey , where EFrom the reaction\u2013diffusion stability, Equations (3) and (4) become an eigenvalue problem ,28,29,30positive . This maFor a finite system of size Equation (5) is necessary, but not sufficient, to satisfy Equation (8).New structures are favored for smaller values of the set n embryo .The generalization of Equation (8) to small spatial dimensions of one or two is direct ), as follows:Equation (8), concerning the generation of new structures from For practical purposes, it is convenient to write the stability parameter Equation (8), for the generation of structures, is straightforwardly reformulated as:Note that Equation (10) formally generates a sphere in the The work thus far has been mostly concerned with the physics and chemistry aspects of the patterns. The next section incorporates the concept of heredity discussed in Temporal continuity, or memory, is, in principle, intrinsically related to reaction\u2013diffusion equations, such as Equations (1) and (2), where the initial conditions formally define the time evolution. However, heredity is not only connected to the continuous history of a system, but is also related to the formation of new structures, diversity, and viability. In this sense, I proceed, as in statistical mechanics, by adopting the notion of equivalent configurations ,13,14,15We are locking, according to pattern diversity, in such a way that some equivalent structures, eventually, are not eliminated (viability) in open systems. This process of selection can include intraspecific competition for chemAs in statistical mechanics, for the set of integers r-sphere ,13,14,15In the case of a physical interface, such as a smooth rock surface covered by slime ,11, d=2 imension ,39,40,41As long as Moreover, this is useful in making estimations (next section). Concerning the concept of heredity, a large number of equivalent structures Finally, I briefly consider the physical substrate, where a variety of structures can develop. External constraints on a given material can generate cracks under appropriate stress conditions , e.g., cd stress ,48,49. E(a)2/s corresponding to biological molecules, such as ribonucleic acid (RNA) [id (RNA) ,8 at 25 id (RNA) ,11,50.(b)A protocell of size (c)As an estimation, The following parameter values are used in making estimations:At an arbitrary spatial dimension Using the values previously mentioned and Equation (14), the characteristic time: The main graph in surfaces and relaIf ro-state ,13,14,15In the above expression, the number of configurations is divided by the dimensionless surface to avoid the equivalent of Gibbs\u2019 paradox 12. The Boltzmann\u2019s constant dynamics ,13,14,15dynamics .According to the equipartition principle in thermodynamics ,13,14,15(a)If the spatial dimension is en d~2.5 .(b)In the same way, for a spatial dimension of (c)As a geologic example, in the Atacama Desert of Chile, rock temperatures vary between approximately 0 and 45Accordingly, the following results are obtained from Equation (18) and the inset curve (i.e., In summary, a spatial dimension of iversity .The stability rate obtained . The estWhen variations in the thermodynamic primitive environment are considered, from stability arguments, physical substrates containing proto-tissues with an integer spatial dimension of two or three are associated with thermal fluctuations. In contrast, for fractional dimensions at approximately As stated in the introduction, the question of \u201cwhat is life?\u201d were not touched upon during this work and are difficult to answer. Nevertheless, these ultimate questions were the motivation for the present work. Interesting efforts, some of which are controversial ,55,56,57Finally, several groups are investigating protocell aggregates ,65,66,67"} +{"text": "Correction to: BMC Musculoskelet Disord 22, 212 (2021)https://doi.org/10.1186/s12891-021-04080-4\u201cThe Ergon\u00ae IASTM technique was created at the Department of Physiotherapy of the University of Patras, where it is taught both in undergraduate and postgraduate level as well as in external educational programs. The authors KM, AP, and KF have participated in developing and disseminating this specific program. In the present study, the authors KM, AP, and KF participated exclusively in designing this study and methods, and they were not involved in the application of therapeutic interventions, measurements, and/or data handling\u201d.Following publication of this article , the aut"} +{"text": "Burnout, a reaction to chronic emotional stress, affects health and reduces the quality of service. Reportedly, healthcare professionals are especially vulnerable to burnout. This meta-analysis is aimed at examining the factors associated with occupational therapists' burnout. The results of 2,430 occupational therapists, across 17 peer-reviewed English articles, the most recent published in 2020, were analysed. Results revealed significant associations between related variables and burnout. Marital status, work field, and work hours, job challenges, patient age, position, turnover intention, working type, and work addiction showed significant positive correlation effect sizes in relation to burnout, whereas age, education, engagement, job satisfaction, personal identity, professional identity, rewards, and feeling valued showed significant negative correlation effect sizes. The results of this meta-analysis suggest that strategies to reduce occupational therapists' burnout need to consider organizational as well as psychological aspects. As the quality of services provided in hospitals and the demand for patient satisfaction increase, so are the organizational efforts to control emotional expression when providing services. As a result, such efforts can bring about conflict between the emotional labour of the members of the organization and the role they play and may lead to burnout by reinforcing a negative attitude toward the job and organization \u20133. BurnoHealthcare professionals are reported to be particularly vulnerable to burnout , 7. OccuPsychological exhaustion among occupational therapists is a critical problem that necessitates counteractive measures because it threatens their psychological well-being and is difficult to reverse. Therefore, it is important to develop preventive measures to reduce the incidence of burnout and its promotional factors in order to prevent individuals from becoming psychologically exhausted . StudiesHowever, since it is difficult to present comprehensive results on the factors that affect burnout through a single study, it is necessary to synthesize and analyse the results of previous studies related to burnout among occupational therapists. For this reason, findings from different studies on burnout are often reported together. For instance, Park and Shin performeSuch studies are suitable for presenting implications according to the variables investigated in the study, such as gender, age, and career; however, they are insufficient for a comprehensive and systematic scientific verification of the variables that affect the burnout of occupational therapists. In addition, individual studies are conducted in different populations, using different tools, sampling methods, and statistical methods, and the characteristics of these individual studies may result in association found in these individual studies may contradict each other. For example, previous studies on the effect of gender on possession showed conflicting results, and for this reason, Purvanova and Muros conducteMeta-analysis is a research method that is aimed at analysing and integrating several individual studies conducted on the same topic . It usesThe articles to be included in the meta-analysis of factors affecting burnout among occupational therapists were selected through a search of electronic databases ProQuest, PubMed, CINAHL, EBSCOhost, and Science Direct . The keyword combination \u201coccupational therapist\u201d and \u201cburnout\u201d was used. Through this process, a total of 344 articles were identified, which were then reviewed according to the following selection criteria: first, study participants were occupational therapists; second, the dependent variable was burnout; third, article was published in academic journals; fourth, article provided necessary data for calculating the effect size; fifth, article was published in English. The article selection process is presented in The coding variables included author, publication year, burnout, burnout-related variables, participant characteristics , and burnout measurement tools. To check the direction of coding in each article, a coding standard was set, and articles with a different direction from the standard were recoded. The coding was as follows: gender, male \u201c0\u201d, female \u201c1\u201d; position, staff \u201c0\u201d, supervisor \u201c1\u201d; work field, small hospital \u201c0\u201d, large hospital \u201c1\u201d; marital status, unmarried \u201c1\u201d, married \u201c0\u201d; working time, full-time \u201c0\u201d, part-time \u201c1\u201d. Variables with only one effect size, specifically recession effect, control, community, fairness, and problem-solving, were coded as other. The three subdomains of burnout were coded for Maslach Burnout Inventory (MBI), and others were coded as two or more subdomains. A research assistant and the researcher performed coding for five articles , and the reliability between the coders was calculated for each coding variable. Reliability was calculated by dividing the coincidence frequency by the sum of the coincidence and disagreement frequencies and multiplying by 100. The reliability between the coders was 93.75% to 100%. Consensus was reached through discussions between researchers on inconsistent variables. One study, namely, Kim et al. , reporteThe Quality Assessment and Validity Tool for Correlational Studies developed by Estabrooks et al. was usedZ, exceeding 2.58 (99% confidence level). There were no outliers with residuals above 2.58, and all effect sizes were thus included in further analyses.Since extreme effect size values can cause a decrease in the reliability of the effect size, in this study, outliers were analysed to calculate a reliable effect size, and the effect size showing an outlier was excluded from the analysis. Outliers were evaluated through a review of residuals, and the criterion for judgment was the standardized residual value, N, which is aimed at establishing the stability of meta-analysis results, and examined the funnel plot. At a significance level of 0.05, the fail-safe N, which refers to the number of articles to be added for the effect size to be meaningless, was 228. Rosenthal [p = 0.78), which indicated absent publication bias.To verify the publication bias, Rosenthal evaluateosenthal suggestep value derived through this test was used as a reference value for the test of heterogeneity [Q-test yielded a Q value of 1701.075 (p < 0.001), which means that the included studies in this meta-analysis were heterogeneous. Based on these results, a random effect model was employed in this study.To calculate the effect size, an effect size calculation model should be selected. There are two calculation models, a fixed effect model and a random effect model. Depending on which model is selected, the estimation and the precision of the effect size vary. The choice of model depends on whether the articles to be analysed are heterogeneous or homogeneous. In this study, a heterogeneity verification test was used, and the ogeneity . The resZ-transformation was performed [The first step in a meta-analysis that presents the aggregated results of individual research results is the calculation of the effect size for each individual study. In the individual studies related to burnout among occupational therapists, there were cases in which the applied study design involved the comparison of burnout between groups and cases where a correlation coefficient was derived . To present comparison results between groups and for synthesizing all related research results, the standardized mean difference effect size was first calculated, and then, Fisher's erformed . The efferformed .The characteristics of the 17 included studies are described in Samples' ages generally ranged from 20 to 60 years; however, five studies did not report age, and four studies reported the mean age of their samples (32.0\u201344.5 years). Samples possessed an extensive range of years of experience, between 0 and 28 years, with four studies reporting only the mean years of experience (7.5\u201317.4) and three studies reporting no data on experience. Out of the 17 studies, 3 reported only one burnout-related variable, while the rest reported two or more related variables.Z = 0.452, 95%CI = 0.307\u20130.597), marital status , patient age , position , turnover intention , working type , work addiction , work field , and working hours . Among the positive significant effect sizes, the effect size of marital status, work field, and work hours was small, and that of job challenges, patient age, position, turnover intention, working type, and work addiction was medium. The variables with significant negative effects on burnout were age , education , engagement , job satisfaction , personal identity , professional identity , and feeling valued . All negative significant effect sizes were medium.The overall effects of related variables on burnout are presented in This study is aimed at verifying the effect size of variables related to occupational therapists' burnout through a meta-analysis. To achieve this, quantitative relations between burnout and its associated variables reported in previous studies were analysed.Occupational therapists' burnout has been the subject of several studies, and many factors including challenges to professional identity, the emotionally demanding nature of mental health practice, lack of professional mentoring, and a lack of awareness of the value of the profession have been presented , 39, 40.Overall, marital status (unmarried), work field , work hours, job challenges, patient age, position, turnover intention, working type (part-time), and work addiction were associated with a higher level of occupational therapists' burnout. Conversely, age, experience, education, engagement, job satisfaction, personal identity, professional identity rewards, and values were associated with a lower level of occupational therapists' burnout.Significant associations among personal variables were with marital status, position, age, and education, although there was no large effect size. Maslach and Jackson reportedAdditionally, significant associations among the organisation-related variables were with patient age, work field, work hours, working type, and reward. The effect size of reward was medium, while the others were small. Reward refers to the compensation that employees receive for the time and effort given to the organisation . The effIn addition, significant associations among the psychological variables were with job challenges, turnover intention, work addition, engagement, job satisfaction, and personal value; the effect sizes of job challenges, job satisfaction, professional identity, and turnover intention were medium. Research on job challenges seems to have yet to reach conclusions. While job challenges can be positively related to ill-health (stress and burnout) as well as well-being (motivation and job satisfaction), as they lead to lower commitment to achieve goals, they also demand satisfaction, which motivates employees to work hard . The resThe strength of this study was first a meta-analysis of the factors associated with burnout among occupational therapists. Among the personal variables related to burnout, those that had a positive association were marital status and position, and those with a negative association were age, education, and experience. All of the organisation-related variables, except for reward, were found to be associated with high level of burnout. Among the psychological variables, higher job challenges, work addition, and turnover intention were found to be associated with high level of burnout, while higher levels of engagement, job satisfaction, personal and professional identity, and feeling valued were found to be associated with low level of burnout. Among the related variables, psychological variables showed a relatively large effect size. As can be seen from the results, among the variables that affect burnout in occupational therapists, the number of personal variables was small and the effect size was also relatively small, whereas the number of related organisational and psychological variables and their effect size were relatively large. These results suggest that a strategy to reduce burnout in occupational therapists is needed. Occupational therapists' burnout can affect not only their quality of life but also the quality and effectiveness of treatment services. It is expected that intervention programs and policies to reduce the burnout of occupational therapists can be designed considering the factors found to be significantly associated with burnout among this population."} +{"text": "Dear editor,Currently, scurvy is an uncommon disease, but it still exists, especially in groups at risk for hypovitaminosis. The authors report the case of a male patient, 63 years, hypertensive, diabetic, with chronic renal failure on hemodialysis for five years. He complained of asymptomatic lesions with progressive increase in the last two months, mainly in the lower limbs. In addition, he reported weakness, episodes of epistaxis, and reported food intake limited to sandwiches and other carbohydrates, denying consumption of fruits and vegetables. On physical examination, he had purpuric areas, plaques and isolated, mostly punctiform with perifollicular location, affecting the lower limbs , upper lScurvy is caused by ascorbic acid (vitamin C) deficiency; vitamin C is found in fresh fruits and vegetables. Ascorbic acid plays an important role in the formation of collagen and extracellular matrix, leukocyte function, iron absorption, folic acid metabolism, and other enzymatic processes. Anomalies in the collagen structure disrupt the integrity of the hair, connective tissue, and blood vessels, leading to the characteristic skin manifestations of scurvy. The initial complaints, after one to three months of deficiency, are usually weakness, malaise, arthralgia, anorexia, and emotional liability. Capillary frailty predisposes to purpura, more frequent in the lower limbs, petechiae, ecchymosis, gingival bleeding, epistaxis, and bone hemorrhage. The diagnosis of scurvy is clinical, confirmed by low serum levels of vitamin C. Symptoms usually occur with plasma concentrations below 0.2\u202fmg/dL. The prognosis for scurvy is excellent. Scurvy is probably underdiagnosed, although its manifestations are relevant to various medical specialties. It is remembered as a disease of ancient times, studied in high school and in history books, and not as a real diagnostic possibility. Attention should be paid to those patients with risk factors for nutritional deficiency, so that the classic findings of scurvy, an easily treatable disease, can be identified early.None declared.Paulo Ricardo Martins Souza: Approval of the final version of the manuscript, drafting and editing of the manuscript, effective participation in research orientation, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, critical review of the literature, critical review of the manuscript.Let\u00edcia Dupont: Approval of the final version of the manuscript, design and planning of the study, drafting and editing of the manuscript, critical review of the literature, critical review of the manuscript.Felipe Eduardo Rodrigues: Drafting and editing of the manuscript, critical review of the literature.None declared."} +{"text": "The resulting societal challenges are manyfold, including changes in consumption patterns, patterns of work and retirement, healthcare issues, and prevalence of chronic diseases and disabilities. Among the latter, mental health is of paramount importance. Indeed, already \u201chealthy\u201d or \u201cnormal\u201d aging is accompanied by an age-dependent cognitive decline. Moreover, many older adults experience mental disorders, including but not limited to depression, anxiety, or dementia. Therefore, an in-depth understanding of physiological changes that occur during brain aging is crucial.The rise in life expectancy together with decreasing replacement fertility are causing rapid aging of western societies. In Germany, for example, 47% of the population are expected to have an age of 50 + already in 2035 physiological brain aging including changes in energy provision [This issue of rovision , the agerovision , 14, agirovision , 17 as wrovision , 16, 17 rovision , 15.Physiological aging is associated with a number of challenges to brain homeostasis including the intensification of oxidative stress, compromised bioenergetics, increased levels of pro-inflammatory substances, low-grade immune activation, modified functional properties of main immune cells of the drain, changes in the glymphatic system (responsible for the life-long waste collection), vascular aging, and arterial stiffness, etc. , 14, 17.At the same time, the aging brain possesses remarkable resilience and adaptivity, allowing it to cope with the listed above problems. Indeed, already one of the very first epidemiologic studies, which was published in Cambridge in 1889 and included 900 oldest old , concluded that the brain is preserved much better than many other physiological systems and represents one of the highlights \u201cin the centenarian landscape\u201d . In thisAlthough aging per se is not considered as a disease, it is a major risk factor for cerebrovascular and neurodegenerative diseases, which are associated with high morbidity and mortality , 3, 15. Importantly, the brain seems to age in a sex-specific manner, with gender being among the susceptibility predictors for several age-related disorders. AD, for instance, has a higher 1.6\u20133:1) prevalence in women compared to men, whereas PD has a higher (3.5:1) prevalence in men compared to women :1 preval, 15, resFinally, many articles of this special issue compare aging of brain architecture and function between humans and commonly used laboratory animals (rats and mice) \u201315, 17."} +{"text": "In the original article, we neglected to include the funder Ricerca Finalizzata Grant (RF-2010-231-8508) to Elisabetta Ferraro.In the published article, Stefania Gorini was not included as an author and she should have the affiliation Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Pisana, Rome, Italy.Stefania Gorini was not included as an author in the published article. The corrected Author Contributions Statement appears below.RB and EF designed the experiments. RB, AB, LD, MR, SM, and SG performed the experiments and analyzed data. RB, AB, LD, MR, SM, and EF interpreted the data. AT, MC, and AM contributed to the development of the study by the provision of study material and data interpretation. AM, MM, PC, ML, and EF wrote the manuscript and provided the financial support. EF conceived the study. All authors contributed to the manuscript revision, read, and approved the final version of the manuscript for submission.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, an author name was incorrectly spelled as Fangrui Mo. The correct spelling is Fanrui Mo.In the original article, there were some errors in the affiliation list. For affiliation 2, instead of \u201cDepartment of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, China\u201d, it should be \u201cDepartment of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, China\u201d.For affiliation 5, instead of \u201cDepartment of Cardiology, The Forth Affiliated Hospital of Guangxi Medical University, Liuzhou, China\u201d, it should be \u201cDepartment of Cardiology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China\u201d.Further, Dr. Xiehui Chen should also be listed as a corresponding author.The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The ranges of variability of elements and stable isotope ratios had slightly different results, according to the three geographical origins considered. In particular, Umbria samples presented significantly lower content of metals potentially dangerous for human health. The results of this first exploratory work highlight the possibility of characterizing tobacco from Umbria, and suggest widening the scope of the survey throughout Italy and foreign regions, in order to be used to describe the geographical origin of tobacco in general and verify the origin of the products on the market.Umbrian tobacco of the Virginia Bright variety is one of the most appreciated tobaccos in Europe, and one characterized by an excellent yield. In recent years, the Umbria region and local producers have invested in introducing novel practices (for production and processing) focused on environmental, social, and economic sustainability. Due to this, tobacco from Umbria is a leading commodity in the global tobacco industry, and it claims a high economic value. The aim of this study is then to assess if elemental and isotopic compositions can be used to protect the quality and geographical traceability of this particular tobacco. For the first time the characteristic value ranges of the stable isotope ratios of the bio-elements as a whole (\u03b4 Nicotiana genus (Solanaceae family) and the general term for any product prepared from the cured leaves of the tobacco plant. Besides its hedonistic use, tobacco plays an important role in other sectors, and has been increasingly investigated in the last few years [Tobacco is the common name of several plants of the ew years . Its alkew years , refinedew years ,4 and haew years , and tobew years . Last buew years ,9,10,11.Nicotiana tabacum leaves. Even if many studies have been conducted to characterize Nicotiana tabacum from the genetic and molecular points of view tobacco production ). In Itaw e.g., ,16), to , to Nicod plants ,18,19,20d plants ,22,23. 13C/12C, 15N/14N) and the site-specific deuterium content of nicotine can provide useful information on the geographical origin of tobacco. Similarly, Binette and colleagues [2H/1H and 15N/14N ratios can be useful for identifying foreign counterfeits of Canadian cigarettes. To date, the elemental composition of tobacco has been investigated mainly to assess the presence of toxic elements that can be inhaled or absorbed through cigarette smoke [In order to support the quality assessment, the chemical characterization has to be coupled with analytical techniques that enable the characterization and traceability of the provenance of tobacco, and that can objectively guarantee it. In this area, however, up to now, very few studies focused on the development of analytical methods able to trace the geographical origin of tobacco ,25. Stablleagues found thte smoke ,22,23. Ote smoke , indeed,te smoke found diNicotiana tabacum have never been extensively explored for their characterization and the verification of their origin. Therefore, the aim of this study is to fill in this gap and start exploring and determining the characteristic value ranges for elements and the stable isotope ratios of the main cultivated tobacco variety (Virginia Bright). In particular, the investigation focuses on Virginia Bright from Umbria, where it has been cultivated for centuries, and where the cultivation is strictly linked to these territories. Furthermore, in recent years in this area, tobacco producers have changed their way of manufacturing, giving particular attention to environmental, social, and economic sustainability along the entire production chain, from cultivation to processing, in order to obtain products of higher quality. The aim was then to assess if the combination of elemental and isotopic compositions, as already successfully applied in the field of food traceability, can be used to protect the quality and geographical traceability of tobacco from Umbria. In particular, this paper contributes to the creation of the very first isotopic and elemental database, also including toxic elements, for Umbrian Virginia Bright tobacco, comparing the obtained data with data of Virginia Bright samples coming from other geographical regions.To date, the stable isotope ratios of H, C, N, O, and S, and the elemental composition of 18O and basically higher values of Be, Pd, Cd, In, and Bi, whereas the African samples showed basically higher values of Rb, Ba, and La. The Argentinian samples presented a higher value of Li, while Brazil had higher values of Mg and Rb. \u03b434S was higher for the United States samples, and lower for the Umbria samples. Hungary showed basically higher values of Mn. Such data were checked using the non-parametric Kruskal\u2013Wallis approach (p < 0.05) to detect statistically significant differences according to the geographical origin. It is interesting to note that, as regards the specific characteristics of tobacco with different geographical origin, despite the geographical proximity of Umbria and Veneto, the Umbrian samples presented statistically different values of \u03b42H, \u03b413C, \u03b418O, \u03b434S, Li, Mo, and Bi from Veneto. The different \u03b42H, \u03b413C, and \u03b418O values can be explained by the latitude effect. Indeed, mean latitude in Umbria is 43\u00b0, whereas Veneto is at a higher latitude of around 45.5\u00b0. According to Dansgaard [2H and \u03b418O values as latitude increases. A similar effect, albeit smaller compared to that of \u03b42H and \u03b418O, occurs also in \u03b413C, and is related to the water stress and light irradiance conditions. Indeed, in warmer climate regions, plants tend to close their stomata under conditions of water stress and high light irradiance, which results in an enrichment in \u03b413C values by a few \u2030 [The isotopic and elemental data variability of tobacco from Umbria, Veneto, and other geographical origins are reported in the ansgaard , the lat a few \u2030 .34S, Li, Mo, and Bi, the content differences by geographical origin can be related to the different geological origin of the areas considered, as well as to the pedological characteristics of the soil and the proximity to the sea [As regards \u03b4 the sea ,34.p < 0.05) between the Umbrian samples and those from Poland and Africa. The results of previous works suggest the usefulness of these parameters in food authentication [It is noteworthy that the concentration of rare earth elements (RREs) in the Umbria samples is generally lower than that of the products from other locations, probably reflecting the different distributions of RREs in the growth soils. The concentrations of RREs are in agreement with the values already reported in other studies on vegetal matrices ,36, conftication .p < 0.05) in Umbria compared to Poland, Veneto compared to Spain, Greece compared to Africa, and Bulgaria compared to Hungary. Furthermore, the Umbria samples were statistically different (p < 0.05) on the basis of the content in Tl (from those of Africa), Th and U (from those of Spain and Poland), and Pb and Te (from those of Bulgaria and Poland).The content of Be, Na, Mg, Cr, Ni, Ga is statistically different between Umbria and Spain, Africa, Hungary, Greece, and Poland. Ge, As, Rb, and Ag resulted as statistically different . Further details about the distribution of the data within each group are shown in the According to d values) was found for \u03b42H, \u03b418O, Li, Na, and \u03b413C (in decreasing order) and for Mo and Bi in the opposite direction. It is interesting to note that the main differences between the Umbria and Veneto samples pertain to the isotopes and the content of elements like Na and Li, which are alkali metals already used for the geographical traceability of food products [34S, Be, Ce, Tm, Mg, and Te, in an inverse relationship. It is noteworthy that many of the elements having a higher impact on the differences between the Umbria and \u201cother\u201d samples belong to the rare earths. In particular, in the comparison between Umbrian and Veneto samples, the highest positive effect in all the elements, except for As, Mo, Pd, Ag, Sn, Pb, Bi, U, Cr, In, Cd, K , Li, Na, Cu, Zn, Sr, Sb, and Rb when compared to Veneto tobacco. Metals and elements are acquired by the growing tobacco plant from soil, fertilizers, and industrial pollution. In addition, metals and elements also derive from tobacco curing treatments and processing Technical Report, 2012). Therefore, the amounts of metals and elements in tobacco products vary widely, depending on the geographical location in which the tobacco leaf is grown, as well as on the treatments administered during the processing . In particular, it should be noted that the content in elements that are potentially dangerous for human health is significantly lower in Umbrian tobacco. Furthermore, Umbrian data for Al, As, Ba, Be, Cd, Co, Cr, Fe, Mn, and Pb were lower overall, whereas Cu and Ni contents were quite similar to data reported by the World Health Organization for cigarette tobacco , therefore indicating a high-quality product in this respect. The same situation was recorded for the Veneto samples, whereas in the case of the \u201cother\u201d group, the content in these elements varies much more, as expected due to the different origins. This point is particularly important, as the World Health Organization recommends regulatory authorities to test cured tobacco in particular for its content in As, Cd, Pb, and Ni, in order to limit human exposure to these particularly toxic elements.More generally, Umbrian tobacco is distinguishable from tobacco with other geographical origins (both the Veneto and \u201cother\u201d groups) by the value of the isotopic ratios of \u03b4the area . Indeed,Due to the encouraging results of the univariate analysis, a multivariate, unsupervised statistical approach was applied by combining the 59 variables together, in order to highlight the factors that contribute to the differentiation between the Umbrian tobacco and tobacco from Veneto and other geographical origins. Principal component analysis (PCA) was performed on data, and the relative score plot is shown in The plot shows that the three classes of samples are partially separated in a projection, which accounts for almost 50% of the variance , with 38% variance explained for the first PC and 10% for the second PC). The isotopic and elemental composition of the Umbrian (blue triangles) and Veneto samples (green squares) are generally different from those of most samples of \u201cother\u201d origins (red dots). In particular, the majority of the samples of \u201cother\u201d origin fall into the region of the PCA, with positive values of PC1. The distribution of the \u201cother\u201d origin samples is much more spread than that of the Umbria and Veneto samples, confirming a more varied isotopic and elemental composition, due to the different geographical provenances. In order to identify the most influential variables that are driving the separation in the multivariate space, the random forest (RF) approach was applied. The outcomes of this analysis were validated with the \u201crandom region\u201d scheme described in the Material and Methods section. The overall efficiency of the classifier is shown in The variables with the most predictive power are reported in 34S, La, Y, Co, Na, Pb, Er, As, Bi, and \u03b42H, showed a consistent role in the models aimed at distinguishing the three groups, suggesting their usefulness as markers of geographical origin. Many of the most important variables in the model are REEs, and their potential use as food tracers has already been determined [In particular, Rb and Tl in primis, followed by Mo, Mn, \u03b4termined ,37,40. ISixty-three samples of Virginia Bright tobacco leaves were analyzed. Of these, 20 samples were from Umbria, 10 from Veneto, and 33 from other geographical origins . Each saBefore the elemental analysis, an aliquot of about 0.5 g was acid-digested after the addition of 4 mL of ultrapure, 67\u201369% nitric acid , by means of a microwave single-reactor chamber equipped with 15 mL quartz vessels, following a multi-step temperature program as described in Bertoldi et al. . Mineral13C, \u03b415N, and \u03b434S in one run, and 0.2 mg in silver capsules for \u03b418O and \u03b42H analysis. The analyses were carried out using an Isotope Ratio Mass Spectrometer equipped with an elemental analyzer for the 13C/12C, 15N/14N, and 34S/32S ratio determinations. The 2H/1H and 18O/16O ratios were measured using an IRMS coupled with a pyrolyser . The isotope ratios were expressed in \u03b4\u2030 versus VPDB (Vienna Pee Dee Belemnite) for \u03b413C, VSMOW (Vienna Standard Mean Ocean Water) for \u03b418O and \u03b42H, air for \u03b415N, and VCDT (Vienna Canyon Diablo Troilite) for \u03b434S, according to the following formula:sampleR is the isotope ratio measured for the sample, and referenceR is the isotope ratio of the international standard; superscript i denotes the mass number of the heavier (higher atomic mass) isotope. The delta values were multiplied by 1000 and expressed in units per mil (\u2030). Sample analysis was carried out in duplicate. The isotopic values of \u03b413C, \u03b415N, and \u03b434S were calculated against in-house working standards 42 and two flours for \u03b434S), which were themselves calibrated against international reference materials: L-glutamic acid USGS 40 , fuel oil NBS-22 , Vienna, Austria), and sugar IAEA-CH-6 (IAEA) for 13C/12C; L-glutamic acid USGS 40 and potassium nitrate IAEA-NO3 (IAEA) for 15N/14N; and barium sulphates IAEA-SO-5 and NBS 127 (IAEA) for 34S/32S. The isotopic values of \u03b42H and \u03b418O were calculated against USGS 54 and USGS 56 standards.Around 4 mg of sample was weighted in tin capsules for the analysis of \u03b413C/12C and 15N/14N, 0.3\u2030 for 18O/16O of bulk, 0.4\u2030 for 34S/32S, and 1\u2030 for 2H/1H.The precision of measurement, expressed as one standard deviation when measuring the same sample 10 times, was 0.1\u2030 for 2). To minimize polyatomic interference, a collision cell was used for Na, Mg, V, Cr, Fe, Ni, Cu, Zn, As, and Eu analysis, while the reaction cell was used for Ca, Ga, and Se analysis.The analysis of 56 elements was carried out with an inductively coupled plasma\u2013mass spectrometer (ICP-MS), the Agilent 7500ce equipped with quartz torch, micromist nebulizer, Ni cones, and an octopole reaction system . Al-, Ca-, Cs-, K-, Fe-, P-, and Rb-certified standard solutions were purchased from CPI International . ICP-MS calibration standard 4 solution and Sc-, Rh-, and Tb-certified standard solutions were provided by Aristar BDH . Multi-element calibration standard 1 and 3 solutions, Hg standard 2A solution, and tuning solution were from Agilent Technologies . A solution of Sc, Rh, and Tb was used as added online internal standard to correct eventual instrumental signal drift during time.++/Ce+ %) were minimized, following the manufacturer\u2019s specification and using an Li, Y, Ce, and Tl solution.Before analysis, the sensitivity, resolution, and P/A factor were optimized, whereas the oxide ratio (CeO/Ce %) and double-charged ratio for each element was calculated as three times the standard deviation of the signal obtained for 10 blanks analyzed in a sequence. All data were higher than the calculated DL, except for Ir, Pt, and Au, which were always below 1.5 \u00b5g/kg, and therefore are not further reported or discussed. Repeatability was determined by preparing and analyzing five samples in duplicate, and by calculating the average coefficient of variation with results below 10% for all quantified elements. Accuracy was obtained by analyzing a certified reference material in each batch, and by calculating the average recovery for each element. Recoveries ranged between 79% and 112%, and were considered satisfactory for the scope of this research.d effect size [Samples\u2019 values were analyzed with R , relying on the following packages for data handling, visualization, and analysis: tidyverse , FactoMiect size . Two mulect size . PCA wasect size and clasThe variable importance in the model was assessed by comparing the ranks of the variable importance in the 500 training/test splits.2H, \u03b413C, \u03b415N, \u03b418O, and \u03b434S, Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hg, Ho, Ir, K, La, Li, Mg, Mn, Mo, Na, Nd, Ni, P, Pb, Pd, Pr, Rb, Re, Sb, Se, Sm, Sn, Sr, Th, Tl, Tm, U, V, Y, Yb, and Zn) of Virginia Bright tobacco samples collected in Umbria, Veneto, and in other geographical areas were investigated. It was confirmed that the main factor influencing the isotopic and elemental signatures of tobacco is its geographical origin. In particular, Umbrian tobacco is characterized by an isotopic and elemental profile that makes it different from tobacco of different origins. Umbrian tobacco showed significantly higher values of \u03b42H, \u03b413C, and \u03b418O, and lower values of \u03b434S, Ag, Al, As, Be, Bi, Ce, Co, Cr, Cs, Dy, Er, Eu, Fe, Ga, Gd, Ge, Ho, In, La, Mg, Mn, Nd, Pb, Pr, Rb, Sm, Sn, Th, Tl, Tm, U, V, Y, and Yb. It is worth noting that Umbrian tobacco has a significantly lower content in elements that are potentially dangerous for human health, like As, Pb, Sn, Be, Cr, and Tl. The proposed machine learning approach has shown strong potential for the geographical classification of tobacco from Umbria on the basis of its isotopic and elemental fingerprint.In this study, the isotopic and elemental profiles (\u03b4The study, if enhanced with a greater number of samples that are representative of the production, will make it possible to develop an analytical model of traceability of tobacco, which can be used to verify the geographical origin of this product on the market."} +{"text": "In the published article, there was an error in the affiliations.Instead of\u201cDepartment of Medical Microbiology and Parasitology, Universiti Putra Malaysia, UPM, Seri Kembangan, Malaysia\u201d it should be \u201cDepartment of Medical Microbiology, Universiti Putra Malaysia, Seri Kembangan, Malaysia.\u201dAnd\u201cDepartment of Biotechnology, Bharath Institute of Higher Education and Research, Chennai, India\u201d should be \u201cCentre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, India.\u201dIn the published article, there was an error regarding the affiliations for Avin Ee-Hwan Koh. They have two affiliations, which are \u201cDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.\u201d And \u201cDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Malaysia.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Polygala paniculata characteristics for evolutionary studies of legume\u2013rhizobia symbiosis, written by Yuji Tokumoto, Kayo Hashimoto, Takashi Soyano, Seishiro Aoki, Wataru Iwasaki, Mai Fukuhara, Tomomi Nakagawa, Kazuhiko Saeki, Jun Yokoyama, Hironori Fujita and Masayoshi Kawaguchi, was originally published Online First without Open Access. After publication in volume 133, issue 1, page 109\u2013122 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to \u00a9 The Author(s) 2021 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The article Assessment of The original article has been updated."} +{"text": "COVID-19 (coronavirus disease 2019) vaccines have become available; now, everyone has the opportunity to get vaccinated. We used Google Trends (GT) data to assess the global public interest in COVID-19 vaccines during the pandemic. For the analysis, a period of 17\u00a0months was chosen . Interest in user queries was tracked by keywords . The geographic analysis of queries was also carried out. The interest of users in the vaccine is significantly increasing. It is focused on the side effects of vaccines, and users pay attention to vaccines\u2019 developers from different countries. The correlation between the scientific publications devoted to vaccine development and such requests of users on the internet is absent. This study shows that internet search patterns can be used to gauge public attitudes towards coronavirus vaccination. Safety concerns consistently high follow an interest in vaccine side effects. This data can be used to track and predict attitudes towards vaccination of populations from COVID-19 in different countries before global vaccination becomes available to help mitigate the adverse effects of the pandemic. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a new human virus that causes COVID-19 (coronavirus disease 2019). The human population does not have the necessary immunity to protect themselves against the transmission of the virus and disease Google Trends (GT) is one of the essential tools for cataloguing internet queries, and this indexed information is available The use of GT in various diseases outbreak is nothing new and has previously been used in infectious diseases such as influenza and Zika virus Corona Vaccine, Corona Vaccine Development, COVID-19 Vaccine Development, China Corona Vaccine, Corona Chinese Vaccine, US Corona Vaccine, UK Corona Vaccine, Korea Corona Vaccine, Russian Vaccine, Sputnik v, Moderna Vaccine, Pfizer Corona Vaccine, AstraZeneca Vaccine, 2019 Novel Coronavirus Disease, 2019 Novel Coronavirus Infection, 2019 Novel Coronavirus, 2019nCoV Disease, 2019nCoV Infection, 2019nCoV, 2019nCoV-co, Coronavirus Disease 2019 Virus, Coronavirus Disease 2019, Coronavirus Disease-19, Covid 19, COVID19 Virus, COVID-19 Virus, COVID19, COVID-19, COVID-2019, SARS2, SARS-CoV-2, Vaccina, Vaccine, Vaccines, Vaccination, Wuhan Corona Virus, Wuhan Seafood Market Pneumonia Virus, Severe Acute Respiratory Syndrome Coronavirus 2, Coronavirus.To assess the status of inquiries related to the coronavirus vaccine, we used \u201cWorldwide\u201d as the search range, \u201c01/19/2020-07/04/2021\u201d as the time range, \u201dAll categories\u201c as the category, and \u201dWeb Search\u201c as the search type. The English terms were selected after searching Naver (the Korean search engine) where we evaluated their popularity. The final selection included the following 39 keywords or possible combinations: We tracked overall interest in keywords on the Internet and then compared interest in terms by country over a selected period. The data is downloaded from the Internet in \u201c.csv\u201d format. The countries with the highest volume of queries always have the highest rankings. The number of queries received is scaled from 0 to 100, depending on the topic's relationship to all searches across all topics. GT uses a relative popularity metric, meaning that the maximum number of queries for the selected period will always be 100. Google's normalized trend data is a useful metric for assessing the popularity of topics as measured by the number of published medical studies. The number of publications was assessed using the PubMed service with the same keywords selected earlier.COVID-19 Vaccine and COVID-19 Vaccine Development . However, for terms like the Coronavirus Vaccine, the Development of a Coronavirus Vaccine, the dynamics are opposite .From August\u00a01st\u00a0till\u00a0December 31st, 2020, the relative search volume for 21 of the 31 search terms significantly increased compared to the period\u00a0from February 1st\u00a0till\u00a0July 31st, 2020. However, nine search terms showed a significant increase in the same period . From Jaelopment A, 1B. Hoopposite A, 1B.TabUS Corona Vaccine, UK Corona Vaccine, Indian Corona Vaccine) periodically observed surges of interest. For example, an increased interest in Russian Corona Vaccine was manifested in the summer of 2020, and interest in UK Corona Vaccine grew in the winter of 2020\u20132021 (Korean Corona Vaccine were not significant (not shown in the figure).Considering the type of Covid-19 vaccines, the period from Jan 2020 to Jun 2021 showed a stable interest in all vaccines of the Russian Corona Vaccine requests come from Russia. After excluding countries that are interested in a vaccine of only one origin, we got Fig. 3.Total (100%) of the The annual trend analysis revealed an upward trend for most of the branded vaccines reviewed .Fig. 4ThSputnik v , Sinovac Vaccine . For AstraZeneca Vaccine there was a power-law trend growth , for Pfizer Vaccine there was exponential growth . For Moderna Vaccine there was exponential growth too .To calculate the trends, a shorter time was used: from May 24, 2020, to Jul 04, 2021 . A polynomial growth is noted for Sputnik v and AstraZeneca by countries was observed in countries such as Argentina, Venezuela, Bolivia, Cuba, Uzbekistan, Kazakhstan, Paraguay, Russia (listed in descending order of the number of requests from 98 to 91%).In countries such as Turkmenistan and Belarus, the users were interested only in the AstraZeneca Vaccine.Countries like Fiji, Barbados, Malta, Jamaica, St Kitts & Nevis, Solomon Islands, Anguilla, Antigua & Barbuda, Vanuatu, British Virgin Islands, Isle of Man, St Lucia, Papua New Guinea, San Marino, Timor-Leste, Grenada, Malawi, Bahamas, Belize, Guernsey, Dominica, Suriname, Bermuda, Jersey, Brunei, Somalia, Bhutan, Rwanda, Seychelles, Eswatini, Sint Maarten, Faroe Islands, Gambia, South Sudan, Lesotho, Gibraltar, Sierra Leone, Andorra, Aruba, Liberia, Cayman Islands, Sudan, Togo, Afghanistan, Madagascar, Senegal, Mali, Guam, Haiti, Macao, Mozambique, Mauritania, Congo \u2013 Kinshasa, Tajikistan, Cote d'Ivoire, Benin, Yemen were only interested in the More than 90% of search queries were for this vaccine in countries such as Trinidad & Tobago, United Kingdom, Ethiopia, Zambia, Ireland, Canada, Namibia, Australia, Saudi Arabia, Malaysia, Cambodia, Nigeria, Botswana, Kuwait, St Helena, St Vincent & the Grenadines, Denmark, Egypt, Iraq, Oman, Uganda, United States, China, Kosovo, Vietnam, Maldives, Singapore, Estonia, Mauritius, Kenya, Jordan, Cyprus, South Africa, New Zealand, Taiwan (listed in descending order of the number of requests from 99 to 90%).COVID-19 vaccine, Coronavirus vaccine according to PubMed monthly data for 2020 , Covid 19 (+39.51%), COVID19 (+38.71%), COVID19 Virus (+20.49%). In addition, the number of requests for the term COVID19 Virus Vaccine increased significantly (+28.47%). The dynamics of weekly recommendations showed a significant increase in interest in the terms COVID-19 Vaccine and COVID-19 Vaccine Development. On the contrary, the number of requests decreased significantly for the Coronavirus Vaccine for the Development of a Coronavirus Vaccine, the number of requests decreased significantly. This is due to the growing awareness of the population about the disease and related terminology.From Jan 19, 2020, to Jan 19, 2021, relative searches for 31 keywords showed a significant upward trend in the number of global searches for terms such as Coronavirus Vaccine from China, USA, UK, Russia, Korea from February 2020 to March 2020, when WHO announced the coronavirus pandemic on March 11. A surge of interest in the Russian vaccine was noted in July-August. In early August, the registration of the world's first coronavirus vaccine was announced in Russia. The growing interest in the vaccine from the UK is since the authorities announced the start of vaccination against coronavirus in early December.There has been a significant increase in the number of requests globally for the terms Sputnik v vaccine. This vaccine prevails in the requests from the countries: Argentina (98%), Venezuela (97%), Bolivia (96%), Cuba (95%), Uzbekistan (94%), Kazakhstan and Paraguay (93%), and Russia (91%).We analyzed vaccine requests where users indicate the country of origin of vaccine development. The example of China shows that the more popular query is the one that includes the name of the country followed by the terms. The geographical distribution of requests for national vaccines was reviewed. It turned out that only the Chinese vaccine is interested in such countries as Kuwait, Singapore, Malaysia, Portugal, Egypt, Brazil, Mexico, France, and Zimbabwe. Only South Korea is interested in the Korean vaccine. 87% of requests for a UK vaccine came from the United Kingdom. Overall, 52% of recommendations for a vaccine from the United States came from the United States, that is, Americans are more interested in vaccines from other countries. Belarus and Turkmenistan are exclusively interested in the AstraZeneca Vaccine. This vaccine dominates among user requests from Trinidad & Tobago, United Kingdom, Ethiopia, Zambia (99%), Ireland, Canada, Namibia, Australia, Saudi Arabia (98%), Malaysia, Cambodia, Nigeria (97%), Botswana, Kuwait, St Helena (96%), St Vincent & the Grenadines, Denmark, Egypt, Iraq (95%), Oman, Uganda, United States, China (94%), Kosovo, Vietnam (93%), Maldives, Singapore, Estonia (92%), Mauritius, Kenia, Jordan (91%), and Cyprus, South Africa, New Zealand, Taiwan (90%).Users of countries of Barbados, Malta, Jamaica, St Kitts & Nevis, Anguilla, Antigua & Barbuda, British Virgin Islands, Isle of Man, St Lucia, San Marino, Timor-Leste, Grenada, Bahamas, Belize, Guernsey, Dominica, Suriname, Bermuda, Jersey, Brunei, Somalia, Bhutan, Rwanda, Seychelles, Eswatini, Sint Maarten, Faroe Islands, Gambia, South Sudan, Gibraltar, Sierra Leone, Andorra, Aruba, Liberia, Cayman Islands, Sudan, Togo, Afghanistan, Madagascar, Senegal, Mali, Guam, Haiti, Macao, Mozambique, Mauritania, Tajikistan, Yemen, some countries of Oceania and Africa are exclusively interested in the For Sputnik v and Sinovac vaccines, a polynomial increase in the number of requests was noted. For Pfizer and Moderna vaccines, an exponential increase in the number of requests was noted. For the AstraZeneca vaccine, there was a power-law trend growth.COVID-19 Vaccine Good.Comparison of publication activity with the number of requests showed no correlation between scientific research and user requests. The analysis showed that users from United Arab Emirates, Singapore, Ireland, South Africa, Israel, Pakistan, Saudi Arabia, and Malaysia were exclusively interested in the vaccine's side effects. User interest in vaccine side effects prevailed in countries such as the United Kingdom (74%), the United States (69%), Australia (64%), Philippines (57%), and Canada (56%). Users from India were the most supportive of the vaccine, with 55% searching for the term WHO has launched an international campaign entitled \u201cManaging the COVID-19 infodemic: Promoting healthy behaviors and mitigating the harm from misinformation and disinformation\u201d to draw the attention of governments to counter the spread of misinformation. One of the main current concerns is the spreading of unconfirmed data about vaccines and vaccination, which could seriously undermine the international strategy to combat SARS-CoV-2. Therefore, the need for new effective and efficient infodemiological methods is more urgent than ever. The relationship between Internet inquiries, media reports, and evidence of morbidity is multifactorial and requires further study. Nevertheless, the main trends in Internet search queries during a pandemic can serve as an additional component of epidemiological surveillance.Rovetta Our research used GT, which shows the search behavior of people using the Google search engine. Future research should consider exploring the same topic on a different search engine including social networks to reach a more diverse user audience.While analyzing the number of requests, we deal not with the absolute, but with the relative number of requests. In addition, this tool does not consider repeated searches from the same user in a short period, distorting the results' objectivity. The limitation of the study is the lack of GT data about China because of the general unavailability of Google in China.Interest in vaccines produced by different countries and companies varied in time and space. For example, the bursts of interest were timed to the announcement of the vaccine registration in Russia (August 2020), and to the announcement of the start of vaccination in the UK (December 2020). There was a geographical differentiation of interest in vaccines produced by a specific country or pharmaceutical company. All applied vaccines are of particular interest to users. We were investigating the use of search engines to gauge user interest in COVID 19 vaccines. Our results demonstrated the potential for using GT as a complementary tool to help understand Internet searches that can determine the demand for vaccines from different countries or companies and the geographic distribution of these demands.This study shows that Internet search patterns can be used to gauge public attitudes towards coronavirus vaccination. Interest in vaccine side effects is consistently high, followed by safety concerns. The flow of inquiries about side effects especially increased in December, when the vaccination company began in Russia, Germany, France, Spain, Austria, Bulgaria, Czech Republic, Italy, Turkey, and other countries. This data can be used to track and predict attitudes towards vaccination of populations from COVID-19 in different countries before widespread vaccination becomes available to help mitigate the adverse effects of the pandemic.The search queries can reflect the interests of users in the field of unreliable information. For example, the testing period for coronavirus vaccines is not yet very long; therefore, due to a lack of knowledge, fakes arise . In addition, the information provided to the public can be politically charged. Statistical processing of information shows more reliable results with an increase in the amount of processed data.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."} +{"text": "Trials in health care are prospective human research studies designed to test the effectiveness and safety of health care interventions, such as medications, surgeries, medical devices and other treatment or prevention interventions. Statistics is an important and powerful tool in trials. Inappropriately designed trials and/or inappropriate statistical analysis produce unreliable results and a lack of transparency when reported, with limited clinical use.This systematic literature review aimed to identify, describe and synthesise factors contributing to or influencing the statistical planning, design, conduct, analysis and reporting of trials.Information sources were retrieved from the following electronic citation databases: PubMed, Web of Science, PsycINFO, and CINAHL and the grey literature repository: OpenGrey. 90 articles and guidelines were included in this review. A narrative, thematic synthesis identified the key factors influencing the statistical planning, design, conduct, analysis and reporting of trials in health care.We identified three analytical themes within which factors are grouped. These are: \u201cwhat makes a statistician?\u201c, \u201cthe need for dynamic statistical involvement and collaboration throughout a trial \u2013 it's not just about the numbers\u201d, \u201cand the \u201caccountability of statisticians in ensuring the safety of trial participants and the integrity of trial data\u201d. While important insights emerged about the qualifications, training, roles, and responsibilities of statisticians and their collaboration with other team members in a trial, further empirical research is warranted to elicit the perceptions of trial team members at the centre of statistics in trials. Such interventions include drugs, cells , surgical procedures, medical devices, behavioural treatments, radiological procedures, and interventions for preventative care . Findings from trials have the potential to change clinical practice, and the care patients receive. For this reason and to minimise harm to patients, trials must be planned, data collected, and analysed for efficacy and safety, to the highest standard. This is best practice for adherence to sound ethical principles.a branch of mathematics dealing with the collection, analysis, interpretation, and presentation of masses of numerical data\u201d and the School of Nursing, Midwifery and Health Systems, University College Dublin, Ireland. The funding source had no involvement in the study design, collection, analysis, and interpretation of data in the report's writing or in the decision to submit the article for publication.Marina Zaki: Conceptualisation, Methodology, Formal analysis, Investigation, Data Curation, Writing- Original draft preparation, Writing- Review and Editing, Visualisation, Project Administration. Lydia O'Sullivan: Methodology, Formal analysis, Investigation, Data Curation, Writing- Original draft preparation, Writing- Review and Editing, Visualisation. Declan Devane: Conceptualisation, Methodology, Writing- Original draft preparation, Writing- Review and Editing, Supervision, Funding Acquisition. Ricardo Segurado: Writing- Review and Editing, Supervision. Eilish McAuliffe: Conceptualisation, Methodology, Investigation, Writing- Original draft preparation, Writing- Review and Editing, Visualisation, Supervision, Project Administration, Funding Acquisition.\u2612 The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u2610The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:"} +{"text": "Sandra Frisenda was not included as an author in the published article. The corrected Author Contributions Statement appears below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.TR, HN, PS, RV, MA, and LB: conceived and designed the research. SF, TR, HN, KR, BK, and LB: performed the experiments. KR and BK: contributed the reagents. TR, SF, PS, RV, MA, and LB: collected and provided the clinical data. TR, HN, BK, PS, MA, and LB: interpreted the data. TR, HN, MA, and LB: performed the statistical analysis. TR, HN, PS, and LB: wrote the initial draft. All authors critically revised and approved the manuscript and are accountable for the accuracy and integrity of the work."} +{"text": "This description interestingly suggests that \u201centrenchment\u201d or \u201csituated fixation\u201d of a course of action could hinder the progress and learning experience of a person, namely\u2014his/her inability and/or unwillingness to adapt to a new context, and/or his/her inflexibility and insistence to stay on course without any intent to change. One example of cognitive entrenchment is observed in professional football, wherein it has been argued that some football coaches are cognitively entrenched within their expert schemas, resulting in their demised game plans and strategic acumen. We advance the study of cognitive entrenchment by proposing an alternative viewpoint, which we term as the \u201cperceived zone of certainty and uncertainty.\u201d This proposition counters the perspective of cognitive entrenchment by arguing that it is cognitive appraisal, judgment, mental resolute, and determination of a person in cognitive certainty of his/her success or failure, or the cognitive uncertainty of success or failure, that would explain the notion of inflexibility and/or unwillingness to adapt, and/or insistence to stay on course without any attempt to deviate. Moreover, we rationalize that certainty of success or failure would closely associate with a feeling of comfort, whereas uncertainty would associate with his/her feeling discomfort. In this analysis, we strongly believe that willingness to change and adapt, reluctance and insistence to remain on course, and/or inclination to embrace flexibility may not necessarily relate to the concept of cognitive entrenchment; rather, inflexibility and/or reluctance to change for the purpose of adaptation has more to do with the desire of a person to seek a state of comfort. Finally, our conceptual analysis of cognitive entrenchment also considers an interesting theoretical concept, which we termed as \u201cperceived optimal efficiency.\u201d Perceived optimal efficiency, similar to cognitive relevance theory, is concerned with the relationship between minimum investment of time, effort, cognitive resources, etc., and an optimal best outcome. The issue for discussion, from our point of view, is related to the extent to which the certainty of success or failure would associate with perceived optimal efficiency.Possessing expert schemas is a positive feat that may yield different types of adaptive outcomes . Limited schemas, in contrast, may deter progress of a novice learner, limiting his/her capability to flourish. Taken as a whole, it may be concluded that expert schemas are more advantageous than novice schemas, differentiating learners in terms of expert and novice. Having said this, however, more recently, researchers have argued that possessing expert schemas could serve as deterrence. Recently, researchers have acknowledged a theoretical concept known as Reconsidering the Trade-off Between Expertise and Flexibility: A Cognitive Entrenchment Perspective\u201d . This cognitive behavior may eventually result in automaticity, enabling the student to successfully solve similar problems without any difficulty. Automaticity, reflecting rote learning, memorization, and excessive practicing, may be viewed as an indication of deep, meaningful understanding of a subject matter, making it somewhat difficult to discount. In this sense, being able to utilize a cognitive strategy without apprehension and/or any indication of uncertainty would, for some, connote evidence of expertise.Recently, an article has been published, titled \u201ce\u201d Dane, , which ie\u201d Dane, . Cognitie\u201d Dane, , p. 583.status quo than to change course, given the probability of his/her uncertainty of success, etc. On this basis, expertise instills confidence, mental resolute, and self-determination, convincing a person to maintain and sustain his/her course of action. Novice schemas, in contrast, could also act as sources of motivation, potentially compelling a person to consider changing his/her course of action in order to improve. From this brief account, we contend that inner satisfaction, gratification, and/or fulfillment of inner needs may explain \u201csituated fixation\u201d or change of a person to his/her own knowledge, understanding, skills, etc. This theoretical account is poignant as it suggests that there are potential reasons, which may account for cognitive thinking, action, and behavior of a person\u2014for example, the willingness to change vs. the insistence to stay on course.Automaticity, success, and ease may all combine to explain and account for cognitive entrenchment . This theoretical premise is logical as it suggests that a person may feel more inclined to stay on course when he/she is well-versed and knowledgeable about a subject matter. Largely, in terms of observation and explanation, a person may feel more at ease with the seek a state of comfort and, by the same token, to avoid a state of discomfort . For example, a university student may choose to remain on course with a specialization despite the objection of his/her family, or the willingness of a musician to change genre may arise from his/her perception of comfort or a desire to seek comfort. With this premise in mind, we rationalize that there are a number of cognitive determinants that could associate with the seeking of comfort of a person\u2014for example, cognitive appraisal, judgment, decision-making, and determination of \u201ccertainty\u201d of a successful course of action. In contrast, likewise, we propose that a perceived sense of uncertainty would intimately link to a state of discomfort. In the latter section of this article, we discuss an important proposition that we term as the principle of cognitive certainty and uncertainty, which considers cognitive appraisal, judgment, and decision-making of a situated context in terms of comfort and discomfort.The focus of this article is for us to introduce and discuss an alternative perspective that may counter the propositions of cognitive entrenchment Dane, , 2011. Wcognitive load imposition , is different from novice schemas, or inexperience and limited knowledge, skills, and/or understanding of and in a subject matter. A novice learner in this case, for example, would exhibit superficial understanding and have difficulties in comprehension and/or adaptation to a new context or a similar situation.Relating to the study of nt Dane, , which int Dane, , cognitint Dane, places e Benner, . Expertinature of schema. The nature of schemas, in this case, delves into the complexity, or quantity and quality, of the schemas of a person . Interestingly, the work of Piaget to a balanced cognitive state of thinking , importantly, reflects the cognitive growth of a person. In relation to academic learning, say, a student may use group discussions, debates, individual exploration, group work, teacher scaffolding, etc., to resolve his/her cognitive conflict the perceived difficulty of a person to adapt, make changes, and/or resolve a new context or situation, and (iii) the reluctance of a person to accept change, criticism, and/or advice.Situated fixation may limit the flexibility of a person to progress and grow cognitively and/or non-cognitively . Many observers have noted that despite his stellar track record , Jos\u00e9 Mourinho has somewhat declined to the point where some journalists and pundits have referred to him as a man of yesterday (source: https://www.the42.ie/is-jose-mourinho-now-yesterdays-man-5140367-Jul2020/). In a recent article published online, for example, Tannoury . This collective insight, interestingly, reflects a potential example of cognitive entrenchment for Jos\u00e9 Mourinho, detailing his inability, inflexibility, and/or unwillingness to adapt to the \u201cmodern game\u201d of football. An article of Grech , likewise, has provided an in-depth analysis of demise of Jos\u00e9 Mourinho and in particular, his personal experience of cognitive entrenchment. Concurring with assessment of Liliane Tannoury, Paul Grech argues that the modern game in football has evolved and the training methodology of Jos\u00e9 Mourinho , which served so well has become obsolete.Upon inspection, there is credence to acknowledge and accept the \u201cnegativity\u201d of cognitive entrenchment, which may apply to different contexts. One non-academic example of cognitive entrenchment recently discussed relates to professional football coaching. Those who follow European football would know the name Jos\u00e9 Mourinho, who is considered to be one of the most revered and decorated coaches of all time may limit the inclination and/or willingness of a person to engage in inventive, innovative, and/or creative acts. Cognitive entrenchment, according to Dane , 2011, mstatus quo may arise from a belief of a person that such \u201cdeviation\u201d would cause chaos and result in a perceived state of uncertainty. Moreover, cognitive entrenchment may instill and/or strengthen the confidence and state of mental resolute of a person, assisting to account for a perception of comfort.Valid and positive reasons for the enactment of cognitive entrenchment in both educational and non-educational contexts are plausible. This consideration is poignant as it posits the possibility that one may purposively \u201cfixate\u201d to a course of action for meaningful reasons. One interesting reason, for example, may relate to the internal desire of a person to experience a \u201cstate of comfort\u201d rather than discomfort. To date, to our knowledge, very little has been inquired into the extent to which seeking of comfort of a person could account for his/her cognitive entrenchment. As a possibility, unwillingness to change from the perception of comfort of a person , stagnated progress, and limited, if any, growth. Taking into account the theory of flow of Cs\u00edkszentmih\u00e1lyi ,b, we coIt is natural for us to want to seek a state of comfort and, by the same token, to avoid a state of discomfort. In academic and/or in school contexts, for example, we contend that a comfort zone is intricately linked to a perceived positive school climate, and/or a classroom climate, espousing the perceptions, feelings, and experiences of emotional support, social safety, academic scaffolding, etc. , as we previously discussed, is a potential example, which could substantiate our rationalization. In this analysis, the inflexibility of Jos\u00e9 Mourinho and his unwillingness to change may relate to a personal need for comfort\u2014that he is more \u201ccomfortable\u201d to use defensive techniques, which have brought him so many successes in the past.One underlying premise of our examination and focus of inquiry entails the plausibility that cognitive entrenchment, or the situated fixation of a person to a well-versed course of action, could intimately relate to a state of comfort. For example, in-depth knowledge of a subject matter may instill a perception of stability, confidence, and optimism in a person, all of which are positive characteristics of comfort. Deviating from a well-versed course of action , in contrast, could give rise to a perception of uncertainty, unsureness, and pessimism, coinciding with a sense of discomfort. The case of Jos\u00e9 Mourinho . In this analysis, we do not view the notion of cognitive entrenchment, or the situated fixation of a person to a course of action, as being negative and/or detrimental\u2014for example, a person's unwillingness and/or reluctance of a person to change a course of action, and/or his/her indication of difficulty to adapt to a new context or situation. Our proposition, in this case, considers the potential positivity or positive \u201creasons\u201d for the seeking of a person to remain fixated to a course of action. One sound and logical reason, as we described, is associated with the desire of a person to seek a state of comfort and, by the same token, to avoid a state of discomfort. In other words, situated fixation to a well-versed course of action may continue to bring success, resulting in a perceived state of comfort . Deviating from a well-versed course of action, in this analysis, could instill unsureness and uncertainty , giving rise to feelings of angst, pessimism, and helplessness. In this sense, striving to achieve a perceived state of comfort would serve as reinforcement, whereas avoidance of discomfort would serve as deterrence to remain on course without any change .perceived zone of cognitive certainty would align with a state of comfort, whereas a perceived zone of cognitive uncertainty would align with a state of discomfort. Foremost from this consideration is the importance of the assessment, judgment, and rationalization of a person, which could warrant and provide justification for the position of cognitive entrenchment . On this basis, our consideration entails the question of whether one is certain , or uncertain, that a continuing course of action would bring success .Our conceptualization for development, taking into account the theoretical concept of comfort (and discomfort) White, considerWe prefer the terms \u201ccertainty\u201d and \u201cuncertainty\u201d as these nomenclature, we believe, would reflect the cognitive maturity of a person, detailing his/her understanding, skills, and experiences of judgment, assessment, and decision-making. For example, there are two possibilities: (i) the ability of a person to make sound and accurate judgment and assess whether a current course of action, drawn from existing schemas, would result in successful outcome(s), and (ii) the mental fortitude, state of confidence, and rationalization of a person to weigh his/her decision regarding the course of action.From our point of view, the cognitive maturity of a person may consist of his/her individual assessment, judgment, and decision-making prior and during the course of an action. Our conceptualization, in particular, considers the extent to which assessment and judgment of a state of certainty or uncertainty could, in fact, account for and/or influence the situated fixation of a person to a course of action. We interestingly make attempts to unify and relate the following: (i) the zone of cognitive certainty with a perceived sense of comfort , and (ii) the zone of cognitive uncertainty with a perceived sense of discomfort .theory of probability is thoughtful, timely, and purposive, serving as evidence of the state of cognitive growth and life wisdom of a person.From the preceding sections, the testament of cognitive certainty of success, or failure of a person, may intimately relate to his/her assessment and judgment, and, more importantly, reflect the process of decision-making. The resolute or irresolute attitude of a person, for that matter, entails some form of risk-taking, which, in this case, consists of a 50\u201350 probability chance . Risk-taking, however, is more than just a \u201cpresent-moment\u201d sense of determination and decision-making. Rather, despite its nomenclature, risk-taking entails the personal characteristic \u201cconsidered weighing\u201d of a person, which we define it as being his/her Cognitive certainty, as we proposed, refers to the assessment, judgment, and rationalization of a person of a context or situation at hand, and whether his/her continual course of action would yield a positive outcome or a negative outcome . This proposition, importantly, emphasizes the cognitive appraisal, mental resolute, and self-determination of a person to take risks and make sound, logical decisions. Risk-taking is an anticipatory feat that could have profound contrasting influences on a person\u2014for example, in terms of positivity, the risk-taking of a university student may facilitate and/or improve his/her mastery of a subject matter, resulting in a state of cognitive certainty, confidence, resolute, and optimism. By the same token, of course, risk-taking may also produce negative returns , giving rise to a state of cognitive uncertainty, pessimism, and low confidence.Details pertaining to the nature of certainty and uncertainty are shown in i. There is cognitive certainty that a positive outcome would be achieved with the continuation of a course of action .ii. There is cognitive uncertainty that a positive outcome would be achieved with the continuation or a change in the course of action of a person .Our conceptualization contends the possibility that a person could, in fact, transpose or \u201cfluctuate\u201d between a state of cognitive certainty and a state of cognitive uncertainty. A context at hand and the subsequent approach of a person to this context, based on his/her existing schemas, may result in two contrasting positionings\u2014that is: a negative position , which depicts the position of cognitive uncertainty of a novice vs. a positive position , which depicts the position of cognitive certainty of an expert. We posit that it is not a clear-cut 50\u201350% chance or probability of risk-taking and self-determination between cognitive certainty and cognitive uncertainty but, rather, as shown, an overlap between the two states. Consider the context of academia in which a university student uses his/her acquired knowledge, life wisdom, and the experiences of other students to change from a state of cognitive uncertainty to that of cognitive certainty. Over time, of course, his/her resolute, decisiveness, and cognitive certainty that Psychology, as a major, would bring positive returns could change to one irresolute, indecisiveness, and cognitive uncertainty. In another context, likewise, a Year-9 student may indicate a state of cognitive uncertainty when learning a topic in Algebra where, over time, with continuing practice and improvement in mastery of using different pedagogical approaches, he/she is able to change his/her mental resolute, conviction, and belief in one of the cognitive certainties. Thus, from our rationalization, we stipulate the following possibilities:A perceived zone of cognitive certainty. Cognitive certainty, or a perceived zone of cognitive certainty, is positive and may, in fact, equate to that of a perceived state of comfort. We define cognitive certainty as an \u201cenvisaged state of decisiveness of a person, reflecting his/her confidence, mental resolute, and self-determination that a chosen course of action would yield either success or failure .\u201d Moreover, we speculate that expertise, unlike novice knowledge, could instill confidence, an appropriate level of motivation, and mental resolute, which, in effect, would determine the cognitive certainty of a person.i. Expertise is advantageous as this would assist a person to remain unchanged during the course of an action, which, in turn, could result in his/her achievement of success or his/her recognition of potential failure. On this basis, we postulate that expert learners with their in-depth knowledge and understanding would more likely associate with a state of cognitive certainty than that of cognitive uncertainty. Importantly, from our point of view, a state of cognitive certainty of success or a state of cognitive certainty of failure would indicate some form of \u201cfinalization,\u201d giving rise to perceived feeling of comfort of a person. In other words, from our proposition, a state of cognitive certainty is more \u201cdefinitive\u201d and \u201cconclusive,\u201d whereas a state of cognitive uncertainty is indefinite and inconclusive, giving rise to a feeling and experience of discomfort, angst, pessimism, etc.A perceived zone of cognitive uncertainty. Cognitive uncertainty, or a perceived zone of cognitive uncertainty, is negative and may equate to a perceived state of discomfort. We define cognitive uncertainty as \u201can envisaged cognitive state of indecisiveness of a person, reflecting his/her lack of confidence, hesitation, ambivalence, and questionable thoughts that a course of action would yield either success or failure .\u201d Moreover, we speculate that cognitive uncertainty reflects the weak mindset of a person, which may espouse a low level of self-belief, mental resolute, and self-determination in terms of decision-making. We speculate that, unlike expert learners, a novice learner is less certain, less resolute, and less confident in his/her cognitive appraisal of a course of action.ii. Moreover, unlike that of cognitive certainty, we propose that cognitive uncertainty may closely align with the perceived feeling of discomfort of a person. Importantly, of course, the limited knowledge and understanding of a subject matter could cause a perceived sense of indecisiveness, reflecting a state of hesitation, ambivalence, and questionable thoughts about the extent to which a person could succeed. In this analysis, from our point of view, a person is more likely to perceive a state of discomfort when he/she adheres and/or expresses a state of cognitive uncertainty. In the context of schooling, a secondary school student who has limited content and procedural knowledge of Algebra, for example, is more likely to express a state of cognitive uncertainty and, correspondingly, a feeling of discomfort .vice versa, correspondingly reflecting a state of cognitive certainty or a state of cognitive uncertainty. What is of interest, however, is the possibility that cognitive certainty and cognitive uncertainty may situate and coexist within a dynamic spectrum.From our examination, cognitive certainty is positive and may equate to the feeling of comfort, whereas cognitive uncertainty is negative and may equate to the feeling of discomfort. We propose that, progressively, with changing knowledge, skills, and experiences, decisiveness (or indecisiveness), mental resolute, and determination may change, which could result in a shift from a state of cognitive certainty to that of cognitive uncertainty, or from a state of cognitive uncertainty to that of cognitive certainty. A person, likewise, may alter and shift his/her feeling of comfort to that of discomfort, or Natural tendency would indicate that, perhaps, we all desire the personal feeling and experience of comfort in life. Comfort, unlike that of discomfort, is positive and produces and/or causes an improvement in different types of adaptive outcomes . Cognitive certainty of success, or cognitive certainty of failure, is conclusive and more definitive, which may account for a feeling of comfort. Cognitive uncertainty of success, or cognitive uncertainty of failure, in contrast, is inconclusive and indefinite, giving rise to a feeling of discomfort, doubt, apprehension, etc. Importantly, from our point of view, both cognitive certainty and cognitive uncertainty may, in fact, associate with the theoretical concept of entrenchment Dane, , 2011. Tdifference in knowledge, skills, and understanding could act as a central driver, which in turn would help govern the mental resolute, self-determination, and state of decisiveness of a person. Moreover, in accordance with our proposition, there are two contrasting zones that a person may purposively choose: the zone of cognitive certainty, potentially giving rise to a state of comfort, which is positive vs. the zone of cognitive uncertainty, potentially giving rise to a state of discomfort, which, of course, is negative.Our proposition, indeed, offers an alternative insight into the potential positivity of the cognitive entrenchment of a person Dane, , 2011. Doptimal best practice the communicative principle of relevance. The cognitive principle of relevance, interestingly, indicates that internal cognitive processes of a person are guided by his/her consideration of efficiency in order to successfully achieve optimal bests in different academic subjects, which then would enable him/her to enter university and enroll in a desired course. \u201cHow much expenditure is enough?\u201d is a personal question that reflects justification, logical decision-making, and sound reasoning . Justification, logical decision-making, and sound reasoning are cognitive attributes that may, importantly, associate with the theoretical concept of perceived optimal efficiency.A desirable feat, of course, would entail and dictate the maximization in an accomplished outcome for the least amount of investment and/or expenditure of time, effort, cognitive resources, etc. An undesirable feat, in contrast, would equate to the minimization in an accomplished outcome for the most amount of investment and/or expenditure of time, effort, cognitive resources, etc. This testament reflects two comparative possibilities: expenditure of time, effort, etc. is \u201cmore\u201d than the outcome that would be accomplished vs. the accomplished outcome is \u201cmore\u201d than the expenditure of time, effort, etc. We argue that, in this analysis, it is more desirable to have a case where the accomplished outcome is more or greater than the expenditure of time, effort, etc. Our theorization of perceived optimal efficiency , we contend, suggests that there is an intricate association between a state of cognitive certainty and a perceived state of efficiency. We argue that, in particular, there is the potential \u201cequivalency\u201d and/or association between optimal efficiency and cognitive certainty.i. The equivalency of optimal efficiency and cognitive certainty is interesting as it considers the possibility and the theoretical tenet that an increase in cognitive certainty could also equate to an increase in efficiency, and, by the same token, a decrease in efficiency would equate to a decrease in cognitive certainty . From our point of view, we acknowledge that there are two possible emphases\u2014namely: (i) self-awareness of the significance of efficiency and/or the insignificance of inefficiency could serve as an important source of information, guiding, motivating, and/or facilitating a person to be resolute and more decisive in his/her decision-making, and (ii) personal resolute, conviction, and decisiveness in justifying a course of action in terms of success of failure , which would give rise to his/her understanding and self-awareness for a need to show efficiency.ii. Inefficiency and state of cognitive uncertainty. Cognitive uncertainty of success or failure, unlike cognitive certainty, is ambivalent and reflects, importantly, a state of indecisiveness, lack of personal resolve and confidence, and self-doubt of a person about his/her belief to maintain and/or to sustain a course of action. Cognitive uncertainty , we contend, suggests that, perhaps, there is an equivalency and/or an intricate association between a state of cognitive uncertainty and a state of inefficiency\u2014for example, inefficiency is equivalent, or analogous, to a state of cognitive uncertainty.The equivalency of inefficiency and a state of cognitive uncertainty, similar to that of the equivalency of optimal efficiency and cognitive certainty, is interesting as it considers two comparative patterns: an increase in cognitive uncertainty would correspond with an increase in inefficiency and likewise, a decrease in inefficiency could equate with a decrease in cognitive uncertainty. This consideration, we contend, may indicate the following understanding between inefficiency and cognitive uncertainty: (i) the indifference of a person to a state of efficiency may reflect his/her lack of motivation and state of disorganization, which then could give rise to his/her indecisiveness, lack of confidence and personal resolve, and/or self-determination in decision-making, and (ii) a state of indecisiveness, lack of confidence and personal resolve, and/or strong conviction to be certain could, in effect, negate and/or limit a person from achieving a state of efficiency.In summary, the preceding sections emphasize a potential relationship between cognitive certainty and perceived optimal efficiency . Moreover, of course, referring to our earlier discussions e.g., , the equpositive life qualities\u2014such as contentment, ease, and satisfaction. A state of Y, in contrast, is undesirable and would indicate the personal experience and feeling of various negative life qualities\u2014for example, discontentment, angst, dissatisfaction, etc.Expert knowledge and skills are integral to the accomplishment of a desirable state of X, which is positive, motivational, and proactive. A state of X, which reflects the intersection between cognitive certainty , efficiency , and perceived comfort may indicate the personal experience and feeling of various Remaining on course without any deviation is encouraged as this cognitive fixation, we contend, would facilitate and strengthen the conviction, personal resolve, and state of decisiveness of a person in his/her decision-making and self-belief that success is definitive. Utilizing existing understanding, knowledge, experiences, etc., likewise, may help advance the progress of a person and/or minimize expenditure of personal resources , resulting in a state of efficiency and/or comfort. This theoretical contention, we contend, may explain the case of Jos\u00e9 Mourinho and his \u201ccognitive fixation\u201d to a specific training methodology, which has brought him immense accomplishments. For example, the personal objective to achieve a state of X , as shown in The study of cognitive entrenchment Dane, , 2011, tOur consideration of expert and novice schemas is somewhat different, resulting in our offering of an alternative viewpoint on the theoretical concept of cognitive entrenchment Dane, , 2011 orOur research development into the advancement of the potential positivity of cognitive entrenchment Dane, , 2011 isFrom the preceding sections, it is evident that continuing research development is needed to advance the study of cognitive entrenchment Dane, , 2011, wThe level of willingness, or unwillingness, to change a course of action .The level of mental resolute, confidence, and self-determination of a person in the belief that remaining on course without any deviation for change would yield success .The willingness of a person vs. his/her reluctance to take risks during the course of learning .Levels of perceived comfort and discomfort .ClA, to assist in the identification of \u201coverlapping\u201d of responses between the willingness to deviate, his/her level of mental resolute, confidence, self-determination, and perceived comfort. In our recent non-experimental study that involved Taiwanese university students, for example, we used cluster analysis to explore the nature of optimal best practice remain steadfast in an in-class intervention ? In a similar vein, could the use of pesuasive feedback encourage personal resolve and conviction of cognitive certainty? It would be of interest then for educators and researchers to consider in-class interventions, which could potentially influence the willingness of a person to change a course of action from T1 to T2. This \u201cexperimental\u201d change, denoted as \u0394 (willingness to change) T2) could, in this case, indicate a state of cognitive entrenchment, whereas, in contrast, the willingness of a person to change, consequently as a result of the persuasive feedback of the teacher would reflect a state of \u201ccognitive dis-entrenchment.\u201dAn experimental design is unique and quite appropriate for some contexts, especially given that this methodology would allow researchers to gauge causal effects and causal flows Rogosa, . Experim1 on Variable B at T2\u2013that is, T1 Var A \u2192 T2 Var B) . It is also valid to consider multiple time points of data collection of the academic performance of a student in a subject matter and his/her corresponding indication of expenditure of time and effort\u2014for example, mathematics quiz (MQ\u2013T1) and expenditure of effort (E-T1) at T1 and mathematics quiz (MQ\u2013T2) and expenditure of effort (E\u2013T2) at T2. A comparison of MQ\u2013T1 and MQ\u2013T2 [i.e., to measure \u0394MQ\u2212T2) and an increase in \u0394E\u2212T2) would, in this case, indicate a state of inefficiency.It is often difficult, for various reasons , to undertake experimental studies in a school or in university. Researchers and educators have consequently resorted to the use of longitudinal, non-experimental designs, which could facilitate and enable the study of growth patterns Bong, . Such loFinally, as one of our reviewers noted, our attempt to establish a new cognitive framework, which would provide a counterargument to the case of cognitive entrenchment Dane, , 2011, iHP and BN contributed equally to the articulation and write-up of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The present review summarizes the studies carried out on this topic in the last five years. According to the new definitions, among all the compounds included in the group of prebiotics, polyphenols are probably the most important secondary metabolites produced by the plant kingdom. Many of these types of polyphenols have low bioavailability, therefore reaching the colon in unaltered form. Once in the colon, these compounds interact with the intestinal microbes bidirectionally by modulating them and, consequently, releasing metabolites. Despite much research on various metabolites, little is known about the chemistry of the metabolic routes used by different bacteria species. In this context, this review aims to investigate the prebiotic effect of polyphenols in preclinical and clinical studies, highlighting that the consumption of polyphenols leads to an increase in beneficial bacteria, as well as an increase in the production of valuable metabolites. In conclusion, there is much evidence in preclinical studies supporting the prebiotic effect of polyphenols, but further clinical studies are needed to investigate this effect in humans. Because microbiota plays such an essential role in human health, it has become a well-researched field over the past 20 years. However, there is evidence about the identification of microorganisms, since 1677, when Antonie van Leeuwenhoek described them as \u201canimalcules\u201d. The relevance and significance of comprehending the interrelationship between host and their resident bacteria populations are extremely necessary to improve the quality of life, prevent the risk of disease, or even treat specific pathologies . MicrobiLactobacillus, Bacillus, Clostridium, Enterococcus, Ruminococcus, Eubacterium, Faecalibacterium, and Roseburia. The second phylum is Bacteroidetes, about 23%, comprising Bacteroides and Prevotella, followed in descending order by the phyla Actinobacteria, about 3% Verrucomicrobia 2% [The human microbiota is composed of bacteria, fungi, archaea, viruses, and protozoans and can be found in many areas of the body; as it colonizes the skin, mouth, vagina, gastro-enteric tube, and/or respiratory system . Over 70robia 2% .Human microbiota differs from individual to individual and is influenced by several endogenous and exogenous factors that can affect the constitution and stability of the microbiome. For example, endogenous factors such as age, genetics, birth gestational date, mode of delivery at birth, infant feeding method, weaning period, hormonal changes, health status; and exogenous factors such as diet, the use of medications, especially antibiotics, exercise frequency, climate, geographical region, pollution level, and the level of stress management ,14,15,16Over the last years, gut microbiota gained more attention, and multiple studies have been performed considering the interaction between the human diet and the intestinal microbiome. All these studies comprise elaborate research, and their applicability to the human microbiota has progressed considerably in terms of food analysis, the interaction between certain bacterial strains, and interaction between specific food compounds ,17.The key roles of the gut microbiota are very important and accomplish essential functions for the host. Among its major roles are: maintaining the structural integrity of the endothelial barrier, influencing the growth of the immune system, providing antimicrobial protection, impacting the metabolism of carbohydrates, lipids, and proteins, and playing an important role in the synthesis of several vitamins such as vitamin K, biotin, cobalamin, folates, nicotinic acid, pantothenic acid, pyridoxine, riboflavin, and thiamine ,7,18,19.In addition to the studies conducted on the intestinal microbiota, there are two essential branches related to intestinal microbiota characterization: prebiotics and probiotics. In the case of prebiotics, these are defined as a selective substrate used by the microorganisms offering many benefits to the host such as protective effects on the gastrointestinal (GI) system, central nervous system, immune system, and cardiovascular system. On the other hand, probiotics are defined as living microorganisms, which also provide health benefits such as preventing bowel diseases, improving the immune system, and alleviating postmenopausal syndrome ,24,25,26Over 25 years ago, prebiotics were identified as a class of compounds with the ability to modulate the gut microbiota, conferring health advantages to the host. Since then, the definition of prebiotics has changed. For example, in 1995, prebiotics were defined by Gibson et al. as \u201ca noIn line with the last definition, a new class of prebiotics that meet the criteria to be categorized as prebiotic substrate , are the polyphenols. The polyphenols\u2019 most essential health benefits are associated with their antioxidant and anti-inflammatory properties. Regarding their role as a prebiotic substrate, the advantages of polyphenols are attributed to the ability of the intestinal microbiota to metabolize phenolic compounds ,30,31,32Polyphenols are described as plants\u2019 secondary metabolites, usually found in foods such as cereals, fruits, vegetables, wine, coffee, tea, and many other derived foods. One of the most common issues regarding the properties of the polyphenols is related to their bioavailability, a parameter influenced by multiple factors, such as food processing, food interaction, dietary intake, distribution, food content, and environmental factors. The quality and the number of benefits offered by polyphenols to the host health have a significant impact, improving the quality of life through their ability to influence the modulation of the gut microbiota ,34,35.This work aimed to review the latest studies that identified and discussed the role of polyphenols as prebiotics in gut microbiota modulation. In addition, we have presented the approaches applied for investigating the relationship between gut microbiota and various human pathologies, especially those connected with the GIT.The majority of prebiotics have carbohydrates as a major component, but there are also other classes such as polyphenols, minerals, and polyunsaturated fatty acids that exert the same prebiotic properties . PrebiotPolyphenols are a large heterogeneous collection of compounds found naturally in vegetables, fruits, cereals, tea, coffee, dark chocolate, cacao powder, and wine. However, they all have a structural unit in common, hydroxylated aromatic rings or phenolic rings . ConsideThe definition of prebiotics is similar to the definition of dietary fibers. However, the definition of prebiotics is differentiated by the selectivity for certain species. Natural sources of carbohydrate-based prebiotics comprise two main categories: dietary fibers and sugar alcohols. In the case of dietary fibers, these include nondigestible starch polysaccharides (with resistant starch), nonstarch polysaccharides, and sugar alcohols (represented mainly by sorbitol and mannitol), which are derived from simple sugars .Regular fruit and vegetable consumption is part of a healthy diet and brings many benefits through their content of phytochemicals, including polyphenols, polysaccharides, and terpenoids. The main ways in which these phytochemicals bring benefits are through their nonabsorbed fraction that acts as a prebiotic and their absorbed part that induces stress resistance mechanisms. The phytochemical class has a broad range of effects, mainly by modulating gut microbiota and maintaining its homeostasis .By comparison with other compounds, such as carbohydrates, lipids, and proteins, phytochemicals are not required for physiological functions , but they can induce biological effects. For instance, after absorption, phytochemicals can improve gut barrier integrity by inducing the expression of tight junction proteins by activating the aryl hydrocarbon receptor in the lumen of the epithelial cells .The evidence of the positive effects of the phytochemicals is constantly growing, especially about polyphenols, as the intake through diet is high, and they play a significant role in gut microbiota modulation. Due to their bioavailability, their effects are closely connected with the food matrix, depending on whether they are consumed as isolated compounds or with the whole food . MoreoveOverall, population statistics present an estimated intake of 900\u20131000 mg/day polyphenols, but this can differ depending on the geographic location and sociodemographics of the targeted group. Among the most frequently consumed sources are: tea, coffee, red wine, fruits, and vegetables. In terms of types of phenolic compounds, procyanidins, flavanols, anthocyanidins, flavonols, and flavanones were among the most frequently identified .The reciprocal interrelation between gut microbiota and polyphenols is a well-known subject of interest, as it can modulate host health. The key factors of this interrelation are the bioactive metabolites. The effect of polyphenols on the intestinal microbiota is achieved by influencing the growth and metabolism of bacteria and by interfering with the cell function of the cell membrane. The majority of the polyphenols can hinder biofilm formation and significant effects via the hindering of bacterial quorum sensing. For example, the flavonol and flavones classes in the Staphylococcus genus can hinder bacterial helicase activities while increasing membrane cytoplasm permeability. Another example is the flavanone-rich citrus extract in combination with the isolated flavanones, as they stimulate a reduction of biofilm formation by inhibiting the quorum-sensing signal mediated by acyl-homoserine lactone. These flavanones can reduce the synthesis of acyl-homoserine lactone and its metabolites ,60,61.Bifidobacteriaceae and Lactobacillaceae and, on the other hand, by reducing the number of pathogenic bacteria such as Escherichia coli, Clostridium perfringens, and Helicobacter pylori [Polyphenols exert their beneficial effects as prebiotic substrate, on the one hand, by increasing the growth and settlement of the probiotic bacterial families such as r pylori ,62, a mer pylori .Akkermansia muciniphila, and F. prausnitzii, observed in mice trials, that had red grapes in their diet. Furthermore, after 16S rRNA gene sequencing, and quantitative PCR on cecal, and fecal samples, an increase of A. muciniphilla, together with a decreased ratio of Firmicutes to Bacteroidetes phylum were observed [Recent studies demonstrated the beneficial effect of polyphenols by stimulating bacteria such as observed ,65. Moreobserved .Lactobacillus reuteri, Lactobacillus acidophilus, Clostridiales, Ruminococcus. Berries are another well-studied fruit group that is well correlated with the prebiotic effect of polyphenols, and it was demonstrated that berries can decrease the expression of IL-1\u03b2, cyclooxygenase-2, nuclear factor k-light chain enhancer of activated B cell, myeloperoxidase, malondialdehyde, and prostaglandin E2, and increased superoxide dismutase and catalase activities [The fruit group represents a specific polyphenol group that is widely studied, and the evidence confirms their prebiotic effects. Red grape extract or grape seeds were observed to have many benefits by increasing tivities ,68.Lactobacillus rhamnosus, Bacteroides, and decrease Clostridiales, Ruminococcus, Coprococcus, Oscillospira [The main sources of polyphenols are carrots, broccoli, beetroot, cauliflower, and potato peel. However, the polyphenol quantity is compared to the fruit group. For example, polyphenols from carrots are much more beneficial to human health when the carrots are consumed entirely, not only as carrot extract. Polyphenols from carrots can increase the growth of llospira . In the llospira .Prevotella, Bacteroides, Enterococcus, and Bifidobacterium in several studies on human gut microbiota [Cloacibacillus, Klebsiella, Alistipes, Akkermansia, and Victivallis, and decreased levels of Blautia coccoides, Bacteroidetes, Subdoligranulum, Anaeroglobus, and Bifidobacterium were also observed [Other food groups with an elevated polyphenol content that have a prebiotic effect through interaction with the gut microbes are the beverages, cereals, pulses , and nuts groups. In the case of the beverages group, there are well-studied compounds such as red wine polyphenols and tea polyphenols. Red wine polyphenols enhanced the concentration of the genera crobiota . After iobserved . In regaobserved as the mobserved ,74.Bidifobacteria, such as F. prausnitzii, Lactobacillus sp., A. muciniphila [L. acidophilus, L. casei, L. delbrueckii, and to decrease the abundance of C. perfringens and Ruminococcus gnavus [For the cereal polyphenol group, compounds such as hydroxycinnamates acid, ferulic acid, coumaric acid were identified. These compounds have the property to enhance the growth of iniphila . The puliniphila . The moss gnavus . The nuts gnavus ,77.It is well known that polyphenols have beneficial effects on host gut microbiota, and on host health implicitly, as it can be observed in Hydroxycinnamic acids represent a major contribution from total polyphenol consumption and have effects on cardiovascular diseases, metabolic syndrome, and colorectal cancer ,80,81. GFrom all plant estrogens, isoflavones have been studied the most, and more precisely, isoflavones from soy and soy products. Other isoflavone sources are green beans, mung beans, and red clover. Isoflavones comprise as main compounds genistein, daidzein, glycitein, and have many beneficial effects in several cancer types, such as breast, and prostate cancer, cardiovascular diseases, osteoporosis, menopausal symptoms, and bone loss ,92,93.Bifidobacterium spp. and Lactobacillus-Enterococcus spp [F. prasnitzii, which is a butyrate producer. It has been shown that the stilbenes class has antioxidant, anti-inflammatory, antitumor, antiplatelet aggregation, cardio-protective, aging delay effects, and enhances a higher gut microbiome diversity [Penicillium spp., HIV, S. aureus, C. botulinum, and hydrolyzable tannins have bacterial activity against H. pylori, by lowering their viability.Initially known for their coloring properties, anthocyanins are a group of polyphenols with health benefits, such as antioxidant and anti-inflammatory actions, reducing the risk of cardiovascular disease, type 2 diabetes, improve weight management, neuroprotection, and can stimulate the growth of ccus spp ,96,97,98ccus spp ,101,102.iversity ,105,106.iversity ,109,110.Micrococcus luteus, Micrococcus lysodeikticus, S. aureus, and Bacillus megaterium [On the other hand, nonabsorbable tannins can reach the colonic microbiota, exerting a prebiotic effect, modulating gut microbiota composition and function, and promoting beneficial bacteria\u2019s growth ,112,113.gaterium ,116,117.Many compounds are produced after the bacterial metabolism of macronutrients and micronutrients in the gut, and the most studied are SCFAs after fermentation of dietary fiber. About 5\u201310% or more of the diet is made of dietary fiber, a nutrient that includes polysaccharides, oligosaccharides, and resistant starch. In the small intestine, they are degraded by the host enzymes. After they pass to the distal gut, they serve as substrates for microbial carbohydrate-active enzymes .Bioactive compounds such as polyphenols can improve both gut health and overall health status, but the gut microbiota must be abundant and diverse for this to happen. Polyphenols are found as glycosides and complex oligomeric structures in plant foods. These intricate structures are metabolized sequentially in the human body . For exaPhenolic compounds are generally found conjugated to glycosides, glucuronides, and organic acids, which can be hydrolyzed by gut microbiota, resulting in aglycones. Consequently, after absorption from the colon, follows transformation into phase II conjugates (sulfated and glucuronidated conjugates) in the intestinal tissues and the liver. Conjugated compounds are excreted into the gut as biliary constituents via enterohepatic recirculation, and before being reabsorbed or transformed, microbial enzymes deconjugate these compounds. Fecal microbial enzymes, \u03b2-glucosidase, \u03b1-rhamnosidase, esterase, \u03b2-gluronidase, catalyze the deconjugation in the gut. Reactions such as ring and lactone fission, dehydroxylation, reduction, decarboxylation, demethylation, isomerization are also reactions induced by the gut microbiota. Microbial transformations are influenced by phenolic structure, flavonoid and nonflavonoid factors, polymerization degree, and spatial configuration ,120.One of the most common polyphenol groups is the flavonoid group. Flavonols, flavanones, flavan-3-ols, isoflavones, and anthocyanins are all members of this category. They all have the same structure: two benzene rings (ring A and B), linked by a heterocyclic pyrone C-ring. In foods, they are found as glycosides, O-glycosides, and C-glycosides, flavan-3-ols, which are not conjugated. Flavan-3-ols can form either proanthocyanidins or condensed tannins as a whole, and either procyanidins, prodelphinidins, or propelargonidins, when they are solely made up of one compound, epicatechin, epigallocatechin, epiazfelechin. Simple phenolics derived from the A and B rings are released after the gut microbiota broke down the C-ring in different positions. The resulting type of phenolic compounds is affected by the hydroxylation pattern and the position of the B-ring. Thus, in phenolic compounds as flavonols, flavan-3-ols, proanthocyanidins, rendering hydroxyphenyl-propionic acids and hydroxyphenyl acid, the C-ring cleavages are produced at 1\u20132 and 4\u201310 bonds or 1\u20132 and 3\u20134 bonds. In flavanones and isoflavone groups, the resulting metabolites show that C-ring cleavage is produced at either position 1 and 2, or 4 and 10. The following steps of flavonoid metabolism carried out by gut microbiota are: demethylation and dehydroxylation reactions. The majority of the resulting metabolites are acid of aldehyde phenolics with one, two, or three hydroxyl and methyl ester radicals, for example, 3--propionic acid from the flavonol quercetin and equol from the isoflavone daidzein ,122.The other group of phenolic compounds is the nonflavonoid group, which, compared to the flavonoid group, has a higher heterogeneity in structure and a higher polymerization level. Compounds such as benzoic acids, hydroxycinnamates, and stilbenes represent this group. Depending on their chemical complexity, they are absorbed to a greater or lesser extent in the small intestine . The mosFurthermore, the gut microbiota also transforms gallic acid and ellagic acid . Gallic Gut microbiota can transform dietary lignans and produce mammalian phytoestrogens, such as enterodiol and enterolactone. The gut microbiota can act on lignans through reductions, demethylation, dehydroxylation, and lactonization reactions. A complex pathway with several precursors, metabolites, diverse conjugation patterns, and different bacteria species is required to obtain the final product, enterolactone, from lignans ,132.Another class of nonflavonoid phenolics, respectively stilbenes, based on a C6-C2-C6 polyphenolic structure, has as a main compound studied, namely trans-resveratrol. The gut microbiota can transform resveratrol O-glucosides such as trans-piceid into resveratrol aglycone through deglycosylation. After absorption, piceid and resveratrol are conjugated in the form of sulfate and glucuronide derivates of the primary circulating metabolites. The first bacterial trans-resveratrol metabolite is dihydro-resveratrol, followed by 3,4\u2032-dihydroxy-trans-stilbene and 3.4\u2032dihydroxydihydro-stilbene ,134.One of the simplest groups of nonflavonoid compounds are hydroxycinnamates, including p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, and their esters with quinic, malic, and tartaric acid. All of these compounds are nutrient substrates for the gut microbiota. Hydroxybenzenes are, after decarboxylation, the final hydroxycinnamate metabolites ,136.The hydroxybenzoic acids, which are predominantly found in fruits, are the most prevalent microbial metabolites obtained in the gut from phenolic compounds, both flavonoids and nonflavonoids. Microbial decarboxylase enzymes convert phenolic compounds, including gallic acid, protocatechuic acid, and vanillic acid to pyrogallol, catechol, and O-methylcatechol when a free hydroxyl group is present at the 4-position. These metabolites can be further conjugated with glycine with an increased urinary concentration of hippuric acid, but most of them are rapidly absorbed in the GIT .In vitro studies on polyphenols have demonstrated through extraction, digestion, fermentation, and other types of chemical and microbiological methodologies that they can influence the resident bacteria, increasing or decreasing their population. In addition, food or food groups that are abundant in polyphenols have been analyzed in vitro in order to check their capacity to influence resident microbiota, with or without their other leading roles, as antioxidants and anti-inflammatories. Detailed information on the in vitro studies published so far can be found in Bifidobacterium, Lactobacillus, Akkermansia, Bacteroides, and Eubacterium, and decreasing the number of Pseudomonas, Salmonella, Staphylococcus, or Bacillus. The mechanism of in vitro studies still needs more understanding, but their high production of SCFAs has been identified in many studies and it can offer a direction for the prebiotic-like effect of polyphenols [Several common phenolic compounds have been observed following the studies conducted on berries. After their extraction and chemical characterization through High Performance Liquid Chromatography (HPLC), compounds such as anthocyanins, flavonols, caffeic acid derivates, ellagic acid derivates, or ellagitannins were identified. A study done in 2020 by Baenas et al. analyzedyphenols .Lactobacillus and Bifidobacterium. Polyphenols were able to be used as a carbon source by these beneficial bacteria. Another review paper, done in 2018 and based on human clinical trials, tested grapes and red wine polyphenols, which showed modifications in the bacteria ratio from gut microbiota. There was an increase of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, Blautia coccoides-Eubacterium rectale groups, as well as a decrease of Actinobacteria, Clostridium spp., C. histolyticum group. In the case of dealcoholized wine intake, an increase in the Fusobacteria, Firmicutes population was noted, and a decrease in the Actinobacteria population [Another type of food with high quantities of polyphenols are grapes. They can be found mainly in the fruit as such, but also in wine or wine by-products, such as grape pomace. The most common polyphenols identified in grapes are quercetin, anthocyanins, anthocyanosides, anthocyanidins, catechins, and proantocyanidins. Previous studies conducted on the fruit, wine, wine industry by-products, and grape extracts have demonstrated the ability of polyphenols to influence the intestinal bacteria, with significant stimulation of the genera pulation ,139,140.Bifidobacterium, Lactobacillus, Dorea, and Lactococcus. In 2019, research evaluating the possible absorption of polyphenols and the antioxidant capacity of a mango by-product snack showed that a snack containing mango peel and mango paste provided a higher amount of polyphenols compared to mango as such [Mango peel is another high-polyphenol food with a prebiotic effect. The main polyphenols are gallates, gallotannins, flavonoids, ellagic acid, gallic acid, mangiferin, and muclurin derivates. In vitro digestion and fermentation were performed on mango peel, and it was demonstrated that it has a high quantity of indigestible fiber that can be fermented, resulting in a considerable quantity of SCFAs. Additionally, it could enhance the growth of as such ,142,143.Bifidobacterium and Lactobacillus-Enterococcus spp., and at the same time increases the production of SCFAs and inhibits the proliferation of Bacteroides and C. histolyticum groups. In 2020, Xu et al. [Firmicutes/Bacteroides ratio, and in 2013, Kerperman et al. [Klebsiella, Enterococcus, and Akkermansia, while inhibiting the growth of Bifidobacteria, B. coccoides, Anaeroglobus and Victivallis [Tea is one of the most popular beverages and is high in polyphenols. Tea has many varieties, such as green, black, and oolong, with the main polyphenolic compounds being catechins, theaflavins, and thearubigins. In 2018, Sun et al. , describu et al. , also den et al. , showed tivallis ,146,147.s in vitro studies, including digestion and fermentation, have demonstrated the polyphenols\u2019 ability to enhance the growth of Enterobacteriaceae, Bacteroides fragilis group, Clostridia, Bifidobacteria, and lactobacilli. Catechol, gallic acid, coumaric acid, and protocatechuic acid have been identified as the main metabolites of pomegranate urolithins. The stability of phenolic compounds during in vitro digestion was also observed. This could be associated with the food matrix, not only with the initial phenolic composition [Another food with a high prebiotic-like effect that can offer many health benefits is pomegranate or different parts of it, such as the pulp, peel extract, or juice. Previouposition ,149,150.Among polyphenol-rich foods, pineapple is another good candidate. In 2021, an in vitro study done on UV\u2013C irradiated pineapple snack bars, performed by Del juncal-Guzman et al. , there wBifidobacterium compared to a high-fat diet [Human gut microbiota has a very complex structure. Due to the fact that clinical trials are not conducted on a number of subjects, it is hard to demonstrate the exact effect of polyphenols in the human body. Therefore, the majority of the viable data translated to humans are obtained from studies performed on animals, usually mice see . In 2019fat diet ,156,157.Bacteroides individuals with a reduction in Bifidobacterium and an increase in Lachnospiraceae, Ruminococcus, and Collinsella. On the other side, in low-Bacteroides individuals they responded with a decrease in Lachnospiraceae, Ruminococcus, and Collinsella, and an increase in Bacteroides, Prevotella, and Bifidobacterium [Another type of fruit rich in polyphenols is cherries. As mentioned before, they are concentrated in anthocyanins, flavonoids, chlorogenic acid, and neochlorogenic acid. In 2017, Mayta-Apaza et al. , identifacterium .Lactobacillus, and butyrate-producing bacteria, and a decrease in E. coli and Enterobacter cloacae were observed in metabolic syndrome subjects. This effect resulted consequently in the reduction of metabolic syndrome risk markers. In another comparative study where similar changes were identified, the results supporting the prebiotic role of polyphenols were obtained from nine participants in a clinical study. Red wine, dealcoholized red wine, and gin were administrated for 20 days, and the first two interventions led to an increase of Bifidobacterium, Enterococcus, and Eggerthella lenta. Bifidobacteria growth was linked to an increase in metabolites derived from wine anthocyanins. Following gin administration, there were no observed modifications [Grapes are a rich source of polyphenols, and the wine industry is a good resource for extracting them, using mainly the pulp of the grapes. Moreover, the wine industry generates impressive quantities of grape pomace, a valuable source of bioactive compounds such as polyphenols. Ten subjects with metabolic syndrome and ten healthy subjects were included in a clinical study. Red wine was administered to both groups. A significant increase in fecal bifidobacteria, ications ,159,160.ications , done onications .Myrciaria jaboticaba or jabuticaba. The main compounds found are Castalagin, vescalagin, procyanidin A, and ellagic acid. In 2021, Fidelis et al. [Firmicutes, Bacteroidetes and Proteobacteria increased. In another study done in 2021, by Trindade et al. [A fruit rich in polyphenols and recently studied for its profile of bioactive compounds is s et al. studied e et al. , in diete et al. ,163.Gynostemma pentaphyllum were administrated. After the administration, an increase of Bacteroides, Lactobacillus, and Bifidobacterium was observed in the treatment group. Additionally, a significant increase in Bacteroidetes/Firmicutes ratio following the consumption of Gynostemma pentaphyllum and notoginseng was observed. The consumption of Gynostemma improved the growth of F. prasnitzii as well. Green tea polyphenols also have an important impact on gut microbiota. Ma et al. [Lachnospiraceae, Bacteroides, Alistipes, and Faecalibacalum were identified as the biomarkers for intestinal redox state, revealing a beneficial impact of tea polyphenols [Tea polyphenols represent one of the most important groups containing bioactive compounds, which can influence the gut microbiota. Whether it is green tea or herbal tea, both can increase and decrease bacteria. A study done in 2015 , analyzea et al. , analyzeyphenols ,164,165.Cyclocarya paliurus and the polyphenols bound to dietary fiber, specifically carrot dietary fiber. Song et al., in 2020, [Cyclocarya paliurus flavonoids in the gut microbiota and on liver clock genes of a circadian rhythm disorder, in a study conducted in mice. It was shown that these types of flavonoids can improve the imbalance of microbial structure in the gut caused by circadian rhythm disruption, and also Firmicutes/Bacteroidetes ratio was significantly decreased in the intervention group. The last described type of polyphenols is the one analyzed in a bound form with dietary fiber, in this case, carrot dietary fiber. In 2020, an in vitro and in vivo study done on polyphenols bound to dietary fiber highlighted that they may contribute significantly to dietary fiber\u2019s fermentation and antioxidant properties through several actions, such as improving gut structure and balance and producing SCFAs [The last two types of polyphenols described in in 2020, describeng SCFAs ,168.Besides the aforementioned polyphenolic groups, there are also isothiocyanates \u2014the most abundant polyphenolic compounds found in cruciferous plants . It was This review concludes that, through recent studies and their integration in the category of prebiotics since 2016, polyphenols can be used to modulate the intestinal microbiota, a role added to their main properties, which are antioxidant and anti-inflammatory. Numerous studies, both in vitro and in vivo, show the interrelationship between polyphenols and gut microbiota. These compounds, not only by their structure but also by the resulting metabolites, are a substrate for probiotics, resulting in the growth of beneficial bacteria and the reduction of pathogenic bacteria, thereby maintaining host intestinal homeostasis.However, it is necessary to develop more studies focusing on the polyphenols\u2019 effects in clinical trials, specifically on their metabolic pathways, the evidence observed mainly in the animal in vitro studies. Using advanced techniques such as omics technologies: metabolomics, genomics, metagenomics, trans-genomics, or proteomics; a better understanding of the polyphenols\u2019 action in the living organisms and their consequent metabolites could be provided. Additionally, their prebiotic effect could be clearly defined and used therapeutically.In conclusion, by summarizing the latest studies that highlight the prebiotic role of the polyphenols, they have the ability to influence both the modulation of the gut microbiota and the host\u2019s general health through their beneficial effects deriving from different mechanisms and impacting multiple organs and systems."} +{"text": "PLOS ONE Editors have been unable to verify the identities, affiliations, contributions and contact email addresses for several of the authors listed on this article [The article .PLOS ONE Editors were unable to verify the updated affiliations.In response to follow-up queries, corresponding authors Zhendong Zheng and Ji J. Yuan stated that there was an error in the original listed affiliations; specifically, Roswell Park Cancer Institute, Georgetown University Medical Center, University of Maryland Medical Center, and University Hospital, University of British Columbia were incorrectly included. Revised affiliation information was provided, but the PLOS ONE Editors retract this article.In light of the above concerns, the JJY did not agree with retraction. ZZ did not respond directly to the retraction decision. GL, HW, TBL, DZS, ZS, SZ, PAP, MLT, GMG, PTM, RSD, AJJ and YMR could not be reached."} +{"text": "To better understand nutrition, food chemistry, and medicine, it is important to investigate biologically active constituents, which requires a detailed knowledge and coverage of the composition of compounds of nutritional and nutraceutical character. The categorization of substances and thus the implementation of specific and dedicated databases have now emerged, based on both analytical data and collected data derived from the literature through a standardized and harmonized approach .Food composition databases aim to produce, collect, and present data in a standardized format to \u201cspeak a common language\u201d, which allows the comparison of data from different national databases to foster an exchange and collaboration between countries ,3. SimulThe development of databases of nutrients, bioactive compounds, metabolites and dietary sypplements are key tools for human health and public nutrition and represent resources for a broad range of applications in different fields, i.e. food, nutraceutical, pharmaceutical, epidemiology and medicinal areas ,10,11,12The initial construction of a dataset of specific nutrients, bioactive compounds, or bioactive compounds\u2019 class and their inclusion in a specified and standardized database should be monitored. Moreover, an update and expansion of the database for a more comprehensive source of data and information is encouraged. Databases dedicated to particular and characteristic categories of foods are also promoted: traditional, certified, and recipe databases ,14,15,16Hoteit el al. , aiming Beltr\u00e1 et al. studied First and foremost, the design and construction of food databases require the exact identification of foods from an adequate food nomenclature and a precise description of the foods. There is a general consensus on the importance of the nomenclature, description, and classification of foods and food groups. A coherent food description system is essential for comparing and/or exchanging data from different databases, and the data of the same nature from different organizations and countries. Moreover, matching procedures for linking different databases should be encouraged .Food composition and other dedicated databases, as well as metabolomic databases and biomarker repositories, represent a unique data resource for nutritionists, dietitians, and researchers for several applications, i.e., dietary assessments, exposure studies, food labeling, epidemiological studies, and clinical trials. Concerning dietary assessment, Witkowska et al. reportedApplications and the utilization of databases from nutrition- and medicine-related fields in other contexts are explored, and current research trends are defined. Delgado et al. describe"} +{"text": "Among invertebrates, jumping spiders are one of the few groups whose representatives have camera-like eyes, and the only group whose representatives have fovea. The latter is present in the camera-like eyes of representatives of some groups of vertebrates, including humans. Based on the literature data, a comparative analysis of the camera-like eyes of jumping spiders and humans was carried out, in the course of which the similarities and differences in the properties and functions of their basic components were identified. The presented data are necessary for the formation of knowledge about jumping spiders as model animals for studying the functioning of the visual system. Bagheera kiplingi Peckham and Peckham, 1896 [All vertebrates, including humans, and some invertebrates have camera-like eyes. However, not all vertebrates have fovea in their eyes, as in humans. Among invertebrates, it is found only in jumping spiders ,4,5,6,7.am, 1896 , are pream, 1896 ,12.As a rule, jumping spiders have four pairs of camera-like eyes of two species: one pair of principle eyes\u2014antero-median and three pairs of secondary eyes\u2014antero-lateral, postero-median and postero-lateral. Each pair of eyes, in addition to features in location, shape, size and structure, has such individual characteristics as the value of the spatial resolving power, color perception, size of the field of view, light perception and the ability to perceive the depth of space. All of them are necessary for jumping spiders to perform different visual tasks, but it is impossible to combine them in one pair of eyes, for example, as in humans, due to their small size ,14. The Portia fimbriata Doleschell, 1859, is 12.5 cycles/degree and has no analogues among animals with eyes of comparable size [max \u2248 377 nm) and green (\u03bbmax \u2248 530 nm) parts of the electromagnetic radiation spectrum, as in Menemerus confusus Koch, 1878 [max \u2248 626 nm) part of the spectrum, as in Habronattus pyrrithrix Chamberlin, 1924 [max \u2248 480\u2013500 nm) part of the spectrum, as in Maratus sp. Karsch, 1878 [max \u2248 430 nm), yellow-green (\u03bbmax \u2248 530 nm) and yellow-red (\u03bbmax \u2248 560 nm) parts of the spectrum [P. fimbriata [Metaphiddipus aeneolus Curtis [M. aeneolus [Hasarius adansoni Audouin, 1826, use their principle eyes to perceive the depth of space due to a unique monocular cue for animals\u2014defocusing images of observed objects on the retina [The principle eyes of jumping spiders are characterized by a high value of the spatial resolving power, color perception, a narrow field of view, a low value of the sensitivity to light and the ability to perceive the depth of space in the same way as the fovea of the human eye, where cones are mainly located ,15,16,17ble size ,20. In mch, 1878 , whereasin, 1924 , and tetch, 1878 . In humaspectrum . Dependiaeneolus . The priaeneolus ,15,16. Je retina . In jumpe retina . Humans e retina ,30.M. aeneolus [Evarcha blancardi Scopoli, 1763 [M. aeneolus [Epiblemum sp. Hentz, 1832 [Epiblemum sp. [max \u2248 535\u2013540 nm) part of the spectrum, as in M. confusus [max \u2248 370 nm) and blue (\u03bbmax \u2248 480 nm) parts of the spectrum, as in H. adansoni [max \u2248 510 nm) part of the spectrum [Trite planiceps Simon, 1899, is estimated to be approximately 330\u00b0 horizontally [In comparison with the principle eyes, the secondary eyes of jumping spiders are characterized by a low value of the spatial resolving power, color perception (only postero-median eyes), a wide field of view, a high value of the sensitivity to light and the ability to perceive the depth of space as well as the peripheral region of the retina of the human eye, where the rods are mainly located ,15,16,17li, 1763 , in posttz, 1832 , and in emum sp. . The retina of the principle eyes of jumping spiders and the fovea of the human eye provide the realization of two identical functions: central (form) vision, which is characterized by high spatial resolving power, and color perception. The retina of the secondary eyes of jumping spiders and the peripheral region of the human retina also provide the realization of two identical functions: peripheral vision, which is characterized by a wide field of vision, and light perception. It should be noted that in jumping spiders, the retina of one of the three species of secondary eyes\u2014postero-median eyes\u2014is able to perceive colors ,15,17,66Thus, the retina of jumping spiders and humans has more different properties and performs more of the same functions .I. completa, do not have a pupil, in contrast with light-loving species, such as P. magnifica [T. planiceps [P. magnifica [Depending on the light conditions of the habitats of jumping spiders, the pupil in their eyes is absent or expressed to varying degrees . So, shaagnifica . In the agnifica . Judginglaniceps and P. magnifica , the pupagnifica . In thesagnifica ,38, in hagnifica . In the agnifica ,38. As magnifica . In humaagnifica ,71,72. Tagnifica . The pupagnifica ,72,74. Tagnifica ,75,76.In jumping spiders and humans, the pupil provides light penetration into the eye ,42. In hThus, the pupil of jumping spiders and humans has more different properties and performs more different functions .M. harfordi [T. planiceps [M. aeneolus [Phidippus johnsoni Peckham and Peckham, 1883 [M. harfordi [T. planiceps [P. magnifica [M. aeneolus and P. johnsoni [M. aeneolus [M. harfordi [P. johnsoni, or 1.41, as in M. aeneolus, in antero-lateral eyes\u20141.43, as in P. johnsoni, or 1.45, as in M. aeneolus, and in postero-lateral eyes\u20141.49, as in P. johnsoni, or 1.51, as in M. aeneolus [In jumping spiders, the lens adheres to the cornea and, judging by photographs of eye sections, for example, harfordi and T. planiceps , occupielaniceps . The lenlaniceps ,68,78,79aeneolus , Phidippharfordi , T. planlaniceps and P. magnifica , in the johnsoni ,38,40. Tharfordi . In jumpharfordi . The lenaeneolus ,27,79.In jumping spiders and humans, the lens performs several identical functions: light-refracting, light-guiding, shaping, supporting and protective ,15. In jThus, the lens of jumping spiders and humans has more different properties and performs more of the same functions .P. magnifica and S. americana, in the principle eyes, epithelial cells are oriented differently and do not form structured layers [P. magnifica [S. americana [M. harfordi [P. magnifica [In the principle and secondary eyes of jumping spiders and human eyes, the vitreous body lies behind the lens and, in comparison with it, occupies a significant part of the eye cavity 1,27,40,4027,40.d layers . It can agnifica , all epimericana , they aragnifica . In thesagnifica ,40. Theragnifica . In humaagnifica ,80. In bagnifica .In jumping spiders and humans, the vitreous body performs several identical functions: shaping, supporting, protective and light-conducting ,66,72. IThus, the vitreous body of jumping spiders and humans has more of the same properties and performs more of the same functions .A comparative analysis of the principle and secondary camera-like eyes of jumping spiders and human camera-like eyes, carried out on the basis of literature data, made it possible to identify the similarities and differences in the properties and functions of their basic components. The outer shell of the eyes and the vitreous body have more of the same properties, while the inner shell of the eyes, the pupil and the lens\u2014on the contrary\u2014have more different properties. The outer and inner shells of the eyes, the lens and the vitreous body perform more of the same functions, while the pupil\u2014on the contrary\u2014more different functions. In general, of the five components considered of the principle and secondary camera-like eyes of jumping spiders and human camera-like eyes, the outer shell of the eyes, the lens and the vitreous body show more similarities, the inner shell of the eyes and the pupil\u2014more differences."} +{"text": "As a common mental disease, depression seriously affects people\u2019s physical and mental health. According to the statistics of the World Health Organization, depression is one of the main reasons for suicide and self-harm events in the world. Therefore, strengthening depression detection can effectively reduce the occurrence of suicide or self-harm events so as to save more people and families. With the development of computer technology, some researchers are trying to apply natural language processing techniques to detect people who are depressed automatically. Many existing feature engineering methods for depression detection are based on emotional characteristics, but these methods do not consider high-level emotional semantic information. The current deep learning methods for depression detection cannot accurately extract effective emotional semantic information.In this paper, we propose an emotion-based attention network, including a semantic understanding network and an emotion understanding network, which can capture the high-level emotional semantic information effectively to improve the depression detection task.The semantic understanding network module is used to capture the contextual semantic information. The emotion understanding network module is used to capture the emotional semantic information. There are two units in the emotion understanding network module, including a positive emotion understanding unit and a negative emotion understanding unit, which are used to capture the positive emotional information and the negative emotional information, respectively. We further proposed a dynamic fusion strategy in the emotion understanding network module to fuse the positive emotional information and the negative emotional information.We evaluated our method on the Reddit data set. The experimental results showed that the proposed emotion-based attention network model achieved an accuracy, precision, recall, and F-measure of 91.30%, 91.91%, 96.15%, and 93.98%, respectively, which are comparable results compared with state-of-the-art methods.The experimental results showed that our model is competitive with the state-of-the-art models. The semantic understanding network module, the emotion understanding network module, and the dynamic fusion strategy are effective modules for depression detection. In addition, the experimental results verified that the emotional semantic information was effective in depression detection. As defined in the free dictionary, depression refers to the act of depressing or state of being depressed. Depression is usually regarded as one type of mood disorder; the main clinical feature of depression is the significant and persistent mood depression. The depressed patients\u2019 emotion can range from gloomy to grief, low self-esteem, and even to pessimism, which may cause suicidal attempts or behaviors . The WorWith the development of the internet in people\u2019s daily life, people began to share their feelings and problems on social media ,4 such aThe goal of depression detection is to classify a person or a post as depressed or not. The performance of depression detection on social media can help with the clinical treatment of depression. This problem needs to be solved. The posts of patients with depression usually contain strong emotions. We give three examples of the textual posts left on Reddit, including two depression-indicative posts and one standard post as follows.Example 1: \u201cToday, I feel so horrible, it makes me want to die I made a fool of myself at work, felt so stupid after the meeting so I left work, told the boss I\u2019m sick. Spent the remaining afternoon in bed.\u201d Label: depressionExample 2: \u201cThat feeling when you hate who you are as a person but can\u2019t get yourself to change because you are so used to being like this for the past several years. I\u2019ve become a shitty person. The thought of change seems impossible to me at this point.\u201d Label: depressionExample 3: \u201cLooking for cool ways to tell parents my wife is pregnant.\u201d Label: nondepressionhorrible, die, and stupid, express strong negative emotions of the author. The words hate and shitty in example 2 also express the author\u2019s strong negative emotions. Example 3 shows the post of a regular user. It does not contain strong negative emotions. As previously mentioned, emotional semantic information usually provides us useful clues for depression detection.Examples 1 and 2 contain strong emotional information made by the patients with depression. From example 1, the words, including . The percentage of negative emotion words was similar. In addition, we calculated the percentages of emotion words in the depression-indicative posts and the standard posts. The depressed users used more negative words than the nondepressed users. At the same time, they used less positive words in their posts than the nondepressed users. It can be concluded from the statistical results that the emotional semantic information may play an effective role for the depression detection task.We also counted the proportion of the positive words and the negative words that appeared in the depression-indicative posts and the standard posts of the Reddit data set , respectDetecting depression automatically has made some progress. Many existing models detect depression based on the feature engineering such as bag of words ,8, latenBefore introducing our model and to understand our paper more conveniently, we give several definitions of concepts, including high-level emotional semantic information, semantic understanding network (SUN), emotion understanding network (EUN), and dynamic fusion strategy.High-level emotional semantic information denotes the emotional semantic information that is captured by deep learning.SUN is a deep learning method that is used to capture the contextual semantic information in the text for depression detection.EUN is a deep learning method that is used to capture the emotional semantic information in the text for depression detection.Dynamic fusion strategy denotes a fusion strategy that can fuse positive emotional information and negative emotional information dynamically.To extract the emotional information effectively, we propose an emotion-based attention network (EAN) for depression detection. Our EAN model mainly contains two modules, including a SUN and an EUN. The SUN module is used to capture the contextual semantic information, which has been widely used in NLP. The EUN module is used to capture the emotional information because the emotional information plays an important role for depression detection as previously mentioned. As shown in The main contributions of this paper can be summarized as follows:We propose a new deep learning framework for depression detection. We also design a special module to explicitly extract the high-level emotion information for depression detection in our framework.We take into consideration the positive emotion information and the negative emotion information simultaneously. At the same time, we apply a dynamic fusion strategy to fuse the positive emotion information and the negative information.We conduct experiments on the Reddit data set for depression detection. The experiments show our model can get state-of-the-art or comparable performance. The ablation study also verifies the effectiveness of the components proposed in our model.In this section, we review the related work about depression detection on social media.In recent years, with the development of social media, more and more people are willing to post their thoughts, emotions, or life details on social media, including Reddit, Twitter, and so on. Park et al showed tDe Choudhury et al collecteMost of the existing methods for depression detection are based on feature engineering. LIWC is usually used to extract individual psychological states, such as positive and negative emotions, pronouns, and so on. Therefore, LIWC was often used for the depression detection task ,12-14. KShneidman presenteDifferent from traditional feature engineering-based methods, deep learning methods mostly apply end-to-end models. Yates et al proposedAccording to previous research on depression detection, it can be concluded that the emotional information is important in the task of depression detection. In addition, deep learning can take high-level semantic information into account, but the current deep learning methods for depression detection still lack effective extraction of the emotional semantic information. Thus, we propose a deep learning model to consider the high-level emotional information that is captured by the deep learning method for depression detection, which is named the EAN.The structure of this paper is organized as follows. The Introduction section introduced the background and related work. The Methods section shows the details of the proposed model. The Results section gives the experiments in this paper. The Discussion section shows the conclusions and future work.As a newly developed social media, Reddit has become a widely popular web-based discussion forum. Reddit users can discuss a variety of topics on this web-based platform anonymously. The topics discussed on the platform can be arranged in more than a million discussion groups. Due to the large amount of discussion text, Reddit attracts many researchers to conduct their studies with the data on the Reddit platform. Pirina and \u00c7\u00f6ltekin built a We preprocessed the Reddit data set, such as removing the stop words. We then counted the occurrence number of each word for the depression-indicative posts and the standard posts. We sorted the words according to the statistics and show the top of the word lists in As shown in Depression-indicative postsAll text: i\u2019m, like, feel, want, get, know, even, really, people, life, i\u2019ve, one, time, think, would, never, depression, me, can\u2019t, go, going, things, don\u2019t, much, friends, make, good, it, still, could, back, anyone, years, anything, always, every, got, someone, fucking, help, day, see, something, work, ever, need, feeling, everything, talk, yearPositive: friends, good, work, help, better, happy, job, love, hard, friend, family, care, wanted, best, sleep, sure, self, mind, understand, new, mental, hope, social, money, high, remember, working, reason, okay, close, real, together, great, normal, deal, believe, change, enjoy, birthday, honestly, nice, motivation, advice, loved, therapist, happiness, fun, boyfriend, saying, bigNegative: depression, depressed, bad, fucking, nothing, alone, hate, shit, stop, lost, worse, anxiety, fuck, tired, sad, die, suicide, kill, relationship, wrong, pain, suicidal, problems, old, sorry, cry, lonely, therapy, hurt, stupid, constantly, issues, sick, crying, problem, afraid, weird, reddit, hospital, worst, hang, illness, dead, scared, dark, broken, shitty, broke, miserable, diedStandard postsAll text: like, i\u2019m, know, friend, would, feel, really, friends, want, time, get, one, even, said, always, never, told, got, family, go, things, me, think, best, make, mom, going, people, years, talk, also, still, back, something, much, see, say, could, i\u2019ve, dad, tell, since, don\u2019t, started, us, me, it, made, help, parentsPositive: friend, friends, family, best, sister, help, friendship, work, brother, good, new, sure, love, wanted, saying, together, advice, father, close, money, boyfriend, kids, care, hard, better, mad, understand, job, basically, happy, great, deal, child, high, moved, believe, fun, social, mind, baby, conversation, eventually, reason, married, big, change, spend, real, normal, niceNegative: bad, wrong, nothing, old, hang, problem, stop, hurt, upset, sorry, shit, issues, lost, alone, cut, angry, hate, problems, worse, depression, weird, sick, constantly, anxiety, sad, tired, annoyed, broke, bitch, scared, died, hell, afraid, crying, cancer, toxic, ignore, pregnant, lose, difficult, wait, fault, depressed, horrible, awkward, selfish, reply, fuck, confused, redditIn this section, we introduce the proposed model for depression detection briefly, which is called the EAN, as shown in The SUN was used to capture the contextual semantic information in the text for depression detection. There are three layers in the SUN module, including the word encoding layer, context encoding layer, and attention mechanism (Att) layer. We will introduce these three layers in more details.w1, w2, ..., nw}, where n denotes the length of the text, and iw denotes the word in the text. In NLP tasks, words are usually mapped to the form of word vectors. Inspired by it, we also encoded every word into d-dimension word vector. We applied the pretrained Global Vectors for Word Representation (GloVe) .Where midhuber , and theH1, H2, ..., nH]. The Att is used to assign higher weights on the important words. We applied the Att to capture the important words in the depression-indicative posts for the depression detection task. The operations of the Att are based on the following equations:The input of the Att layer is H = . It can be trained during the training. We can get the output emoh of the EUN module with the following formula:The goal of the emotion fusion layer is to fuse the positive emotional information and the negative emotional information for depression detection. We get the positive emotional information atth from the SUN module and the emotional semantic information emoh from the EUN module. In this section, we applied a concatenation operation to fuse the contextual semantic information atth and the emotional semantic information emoh as the final representation finalf:As previously described, we get the contextual semantic information Accordingly, the final classification decision for depression detection is formulated by the softmax function:The cross-entropy loss was used for depression detection in our model. The training goal was to minimize the loss.The unit size of Bi-LSTM in our experiments was 64. We applied the pretrained 300-dimension word embedding (GloVe) in the word encoding layer. In addition, the optimization function was Adam, and the batch size was 128. Following Tadesse et al [We applied the standard metrics, including accuracy, precision, recall, and F1-score, to evaluate the effectiveness of our model for depression detection. F1 is defined as follows:We compared the results of our model with many state-of-the-art methods on the Reddit data set. We compared it with the baselines, including LIWC, LDA, unigram, bigram, LIWC + LDA + unigram, LIWC + LDA + bigram , LSTM, BLIWC: Tadesse et al extracteLDA: Tadesse et al extracteUnigram: Tadesse et al extracteBigram: Tadesse et al extracteLIWC + LDA + unigram: The model is based on the aforementioned characteristics, including LIWC, LDA, and unigram, for depression detection.LIWC + LDA + bigram: The model is based on the aforementioned characteristics, including LIWC, LDA, and bigram, for depression detection.LSTM: LSTM was proposed by Hochreiter and Schmidhuber . We applBi-LSTM: The Bi-LSTM was proposed by Graves et al . We applBi-LSTM + Att: The model is based on Bi-LSTM and the Att.EAN: This model is proposed in this paper, which considers emotional semantic information based on deep learning.As shown in The results based on bigram (bigram and LIWC + LDA + bigram) were higher than unigram (unigram and LIWC + LDA + unigram). It can be concluded that contextual information can improve the results of the model. The results based on Bi-LSTM were higher than LSTM. it can be concluded that considering bidirectional contextual semantic information is necessary. The results based on Bi-LSTM + Att were higher than Bi-LSTM; it can be proven that the Att is effective for the depression detection task. The proposed EAN model got the higher results because we took into consideration both the contextual semantic information and the emotional semantic information.In this section, we analyze the effectiveness of the two modules (SUN and EUN), the effectiveness of different emotional semantic information, and the effectiveness of the dynamic fusion strategy.To verify the effectiveness of SUN and EUN, we designed a series of experiments. SUN means the proposed EAN model without the EUN module. EUN means the proposed EAN model without the SUN module. As shown in P value, ACC value, and F1 value. From the experiments, our proposed EAN model obtained the best result compared to the three aforementioned baseline models. It also verified the effectiveness of each proposed module in our framework.To verify the effectiveness of different emotional semantic information, we designed a series of experiments, including without emotion (SUN), without positive emotion (SUN + negative), and without negative emotion (SUN + positive). As shown in To verify the effectiveness of the dynamic fusion strategy, we designed a series of experiments including the EAN model with the concatenate fusion strategy, the EAN model with the fixed fusion strategy, and the EAN model with the dynamic fusion strategy. The EAN (concatenate fusion) model applies the concatenate operation in the emotion fusion strategy. The EAN (fixed fusion) model applies the fixed fusion operation in the emotion fusion layer. The \u03b8 in equation 10 is fixed at 0.5. The EAN (dynamic fusion) model is the model proposed in this paper. As shown in In this section, we designed a series of experiments to verify the effectiveness of the proposed EAN model, including the two modules in the EAN model, the different emotional semantic information, and the dynamic fusion method.Some visualization results of the \u03b8 to illustrate the effectiveness of the proposed dynamic fusion strategy intuitively are shown in Depression attracts more and more attention from people and organizations now. With the development of computer technology, some researchers are trying to use computers to automatically identify people who are depressed. In this paper, we proposed an EAN model to explicitly extract the high-level emotion information for the depression detection task. The proposed EAN model consists of the SUN and the EUN. In the proposed model, we took into consideration the positive emotion information and the negative emotion information simultaneously. At the same time, we applied a dynamic fusion strategy to fuse the positive emotion information and the negative information. The experimental results verified that the emotional semantic information is effective in depression detection.According to WHO statistics, depression is one of the main causes of suicide in the world. We will focus on the relationship between depression and suicide. We will try to combine suicide detection with depression detection in our future work to improve the performance of both tasks by multitask learning. In addition, the future work will be combined with self-reported depressive symptoms or clinical diagnosis. Hopefully, our study can provide some technical supports in the field of health care."} +{"text": "Instead of \u201cFaculty of Sciences, University of Masaryk, Brno, Czechia\u201d, it should be \u201cDepartment of Botany and Zoology, Faculty of Science, Masaryk University, Brno, Czechia\u201d.In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The second and third authors, Biao Lu and Yu Liu, were not listed as co-first-authors in the article as published originally.The Author Contributions statement, published originally read \u201cFL and RC conceived the study design, managed the study, conducted the data analysis, and wrote the manuscript. CS helped with the data analysis and editing of the manuscript. LX, BL, YL, YZ, HW, XH, PH, QZ, YLL, KY, KW, ZG, ZL, JY, HXZ, HZ, ZJ, YJL, NW, CY, JYY, LY, FH, and QY are site investigators and conducted the study in each participating center. All authors contributed to the article and approved the submitted version\u201d. The corrected Author Contributions statement is as follows: \u201cFL and RC conceived the study design, managed the study, conducted the data analysis, and wrote the manuscript. CS helped with the data analysis and editing of the manuscript. BL and YL contributed to the design of the study protocol, training of trial investigators. LX, BL, YL, YZ, HW, XH, PH, QZ, YLL, KY, KW, ZG, ZL, JY, HXZ, HZ, ZJ, YJL, NW, CY, JYY, LY, FH, and QY are site investigators and conducted the study in each participating center. All authors contributed to the article and approved the submitted version.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "These authors should be included because they organized and led the collection of the field data, and they also reviewed and approved the manuscript.Following publication of the article , it was The author list has been corrected in the published manuscript and the correct author list can be found in this correction article. Likewise, the \u2018Authors\u2019 contributions\u2019 statement has been updated in the original article and can be seen in this correction:Authors' contributionsMB, SI, and DD designed the field collection protocols; MB, PM, SI, DD, FG, EG, SC, HT, MM, and MY oversaw the collection of data; MB, GY, EA, DG, SY, AW, AG, EE, TA, DE, SD, MYoh, and WL collected the field data; DY conducted the laboratory work; SI, SZ, and MB analyzed and interpreted the data; MB, SI, and SZ wrote the first draft of the manuscript. DD, MY, and GY provided a critical revision of the manuscript. All authors read and approved the final manuscript.The authors thank you for reading this correction and apologize for any inconvenience caused."} +{"text": "In the originally published article, affiliations 1 and 4 were presented incorrectly.Affiliation 1 was presented as \u201cDepartment of Head Neck and Thyroid Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China\u201d; it should be \u201cDepartment of Head Neck and Thyroid Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China\u201dAffiliation 4 was presented as \u201cDepartment of Radiation Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China\u201d; it should be\u201cDepartment of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Unprecedented and unforeseen highly infectious Coronavirus Disease 2019 (COVID-19) has become a significant public health concern for most of the countries worldwide, including Nepal, and it is spreading rapidly. Undoubtedly, every nation has taken maximum initiative measures to break the transmission chain of the virus. This review presents a retrospective analysis of the COVID-19 pandemic in Nepal, analyzing the actions taken by the Government of Nepal (GoN) to inform future decisions. Data used in this article were extracted from relevant reports and websites of the Ministry of Health and Population (MoHP) of Nepal and the WHO. As of January 22, 2021, the highest numbers of cases were reported in the megacity of the hilly region, Kathmandu district , and Bagmati province. The cured and death rates of the disease among the tested population are ~98.00 and ~0.74%, respectively. Higher numbers of infected cases were observed in the age group 21\u201330, with an overall male to female death ratio of 2.33. With suggestions and recommendations from high-level coordination committees and experts, GoN has enacted several measures: promoting universal personal protection, physical distancing, localized lockdowns, travel restrictions, isolation, and selective quarantine. In addition, GoN formulated and distributed several guidelines/protocols for managing COVID-19 patients and vaccination programs. Despite robust preventive efforts by GoN, pandemic scenario in Nepal is, yet, to be controlled completely. This review could be helpful for the current and future effective outbreak preparedness, responses, and management of the pandemic situations and prepare necessary strategies, especially in countries with similar socio-cultural and economic status. Federal, provincial, and district-level daily cases of COVID-19 in Nepal from January 23, 2020, to January 22, 2021, were obtained from the Ministry of Health and Population (MoHP), GoN,The MoHP of Nepal confirmed the first and second cases of COVID-19, respectively, in January and March, in an interval of 2 monthsn = 144,278) has the highest number of confirmed cases in Nepal, followed by province no. 1 and Lumbini followed by Lalitpur , Morang , and Rupandehi districts and lowest in Manang (n = 20), Mugu (n = 37), Mustang (n = 43), and Humla (n = 44) districts . As depiistricts .n = 72,396), followed by the age group of 31\u201340 years (n = 458) , over half were observed in senior adults (\u226560 years). One early study among the Nepalese children suggested that male children were more commonly infected than female children ; howevern = 458) . A highen = 458) , 14. Oven = 458) . The enhn = 458) , 16. Amon = 184) followed by hypertension (n = 117), renal disease (n = 107), diabetes (n = 77), liver disease (n = 44), and cardiovascular disease (n = 36) , 623 (31.37%), 721 (36.30%), and 642 (32.32%) were with no report of comorbidities, with single comorbidities, and with multiple comorbidities, respectively. In cases with single comorbidities, the highest incidence was reported in respiratory disease ((n = 36) . SimilarGeographically, Nepal is divided into three distinct ecological zones, mountain, hilly, and low-plain land from north to south. Politically, Nepal is divided into 7 provinces, 77 districts, and 753 local bodies. There were multiple peaks of active cases of COVID-19 in Nepal: active cases rapidly increased from early May to early July 2020, then increased slowly up to late July and increased at a higher rate again up to the end of December, and then decreased sharply . The spaNepal has adopted many readiness and response-related initiatives at the federal, provincial, and local government levels to fight against COVID-19. Initially, the government had set health desks and allocated spaces for quarantine purposes at the international airport and at the borders, crossing points of entry (PoE) with India and ChinaThe GoN underestimated both the short and long-term impacts of border closure,As per the cabinet decision on March 25, 2020, Nepal established a COVID-19 response fund, developed a relief package,14. Furthermore, the NPHL organized the training of trainers for laboratory staff in collaboration with the Medical Laboratory Association of Nepal11, 13. Early testing and timely contact tracing are crucial restrictive policies to control the spreading of the SARS-CoV-2 virus and \u201cStandards for Home Quarantine\u201d were imposed for all provinces76 B.S. a-2 virus ; however,,,,,,,,,Ministry of Health and Population engaged in developing, endorsing, improving, and disseminating contextualized technical guidelines, standard operating procedures (SOPs), tools, and training in all other critical aspects of the response to COVID-19, for instance, surveillance, case investigation, laboratory testing, contact tracing, case detection, isolation and management, infection prevention and control, empowering health and community volunteers, media communication and community engagement, rational use of personal protective equipment (PPE), requirements of drugs and equipment for case management and public health interventions, and continuity of essentials services,,,via the involvement of celebrities, doctors, and experts of microbiology and infectious diseases on physical distancing and the importance and use of masks and sanitizers to prevent the COVID-19 contagion. In addition, camping programs were launched by the involvement of youth volunteers of the community in central NepalMinistry of Health and Population and supporting organizations, such as United Nations Development Program (UNDP), UNICEF, and World Vision managed crucial supplies of PPE, facemasks, gloves, and sanitizers to ensure the protection of frontline workers and supporting staffs,,,,,Government of Nepal received funds from the World Bank ($29 million), the United States of America ($1.8 million), and Germany ($1.22 million) to keep people protected from COVID-19 through health systems preparedness, emergency response, and research. In addition, support from UNICEF and countries, including China, India, and the USA, in the form of emergency medical supplies and equipment were received within January 2020 to March 2020. Private companies, corporate houses, business organizations, and individuals have also contributed to the prevention, control, and treatment fund of coronavirus ($13.8 million), established by GoN to cope with COVID-19. The Prime Minister Relief Fund is also expected to be utilized. The GoN allowed international NGOs to divert 20% of their program budget to COVID-19 preparedness and response; for instance, the Social Welfare Council has allocated $226 millionThe GoN has formed a committee to coordinate the preparedness and response efforts, including the MoHP, Ministry of Home Affairs, Ministry of Foreign Affairs, Ministry of Finance, Ministry of Culture, Tourism and Civil Aviation, Ministry of Urban Development, Nepal Army, Nepal Police, and Armed Police Force. The Humanitarian Country Team (HCT) includes the Red Cross Movement and civil society organizations . Under the joint leadership of the office of Resident Coordinator and the WHO, the HCT has initiated contingency planning and preparedness interventions, including the dissemination of communications materials to raise community-level awareness across the country,,However, despite these robust efforts implemented by GoN, few lapses existed. Examples are the following: issues of inconsistent implementation of immigration policies usually at Indo-Nepal borders,,,,,There is no doubt that GoN has taken major initiatives to fight the COVID-19 pandemic. The MoHP, together with associated national and international organizations are closely monitoring and evaluating the signs of outbreaks, challenges, and enforcing the plan and strategies to mitigate the possible impact; however, many challenges and difficulties, such as management of testing, hospital beds, and ventilators, quarantine centers, frontline staffs, movement of people during the lockdown, are yet to be solvedTo strengthen its coordination mechanism, the government formed a team to monitor conditions and measures applied to control the outbreak; a COVID-19 coordination committeeFinally, this study only focuses on analyzing COVID-19 data extracted from the MoHP database for 1 year. Furthermore, we did not quantify the effectiveness of the strategies of GoN and the role of non-governmental organizations and authorities to combat COVID-19 in Nepal.n = 144,278), all of the 77 districts were affected. The cases showing highly COVID-specific symptoms were low (<1%) in comparison with the reports across the globe (This study provides an insight into the impacts of the COVID-19 pandemic from the Nepalese context for the period of first-wave from January 2020 to January 2021. Despite the several initiatives taken by the GoN, the current scenario of COVID-19 in Nepal is yet to be controlled in terms of infections and mortality. A total of 268,948 confirmed cases and 1,986 deaths were reported in one year period. The maximum number of cases were reported from Bagmati province (he globe , which mhe globe . Consisthe globe , 23, thehe globe . SpatialBased on this assessment, in addition to the WHO COVID-19 infection prevention and control guidanceBB: Conceptualization, writing, and original draft preparation. KB, BB, and AG: data curation. BB, RP, TB, SD, NP, and DG: writing, review, and editing. All authors contributed to the article and approved the submitted version.KB and AG were employed by Nepal Environment and Development Consultant Pvt. Ltd., in Kathmandu, Nepal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Olcay K\u0131ro\u011flu. Instead of \u201cPharmacovigilance Specialist, Balcali Hospital, Faculty of Medicines, Cukurova University, Adana, Turkey,\u201d it should be Department of Pharmacology, Institute of Health Sciences, Faculty of Medicine, Cukurova University, Adana, Turkey.In the published article, there was an error in the affiliation for author The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The thermal strain can be measured using subjective methods without the use of sensitive equipment. The purpose of the present study was the development and validation of an observational - perceptual heat strain risk assessment (OPHSRA) method.This cross-sectional study, in 2019, was performed. At first, an observational-perceptual questionnaire was designed using effective items in producing heat strain. Then, the reliability and validity of the questionnaire were examined. Later, 201 male workers were asked to perform the routine tasks for 90\u2009min under various climatic conditions after resting in a cool room. At the end of the activity, the tympanic temperature of the subjects was accurately measured. Also, the designed questionnaire was completed by researchers and participants. Then, the effect coefficients of the items were calculated and used for developing the novel index. At final, the index validity was investigated.R2\u2009=\u20090.69).The values of the content validity ratio (CVR), content validity index (CVI), and Cronbach\u2019s coefficient alpha (\u03b1) of the designed questionnaire with 16 questions were equal to 0.793, 0.913, and 0.910, respectively. The results indicated that environmental, job, administrative, and clothing items assessed by the questionnaire with the coefficients of 0.860, 0.658, 0.783, and 0.566 had significant effects on the thermal strain, respectively. These coefficients were exploited to develop the index. The result revealed that the OPHSRA index justified 69% of the variations of the tympanic temperature (The novel index developed by the questionnaire had an acceptable validity. Therefore, this index can be used for estimating the risk of thermal strain in a variety of thermal conditions. Heat is one of the very common physical harmful agents in a variety of public and occupational environments, such as cement, steel, casting, and food produce industries. Heat exposure becomes a threat to people\u2019s health . ProlongThe efforts to quantify the risk of heat-related health effects have resulted in the development of more than one hundred heat stress indices . The resEffective items in producing heat strain were identified by a literature review through a search in known databases and interviews with the experts of occupational health. Then, those were reviewed and the repetitive and irrelative items were omitted. Improper items for designing the qualitative question were also eliminated. In final, 37 items remained in the study. Those were classified into six groups, including personal, environmental, job, administrative, clothing, and lifestyle items based on the balance theory of job design . Based oIn this phase, a number of questions were generated for assessing the identified effective items. These questions were divided into three parts of observational, descriptive, and perceptual questions. Moreover, several responses were designed for each question. For quantifying the items, equivalent scores for each response were determined using subject-matter expertise, and later, those were modified based on the opinions of several experts. The draft questionnaire of the observational-perceptual heat strain risk assessment (OPHSRA) index included these questions. To develop the questionnaire, it was administered by the researchers. After developing the questionnaire, it can be administered by other people. The descriptive and perceptual questions are also answered by the workers.For evaluating the content validity, the questions were reviewed by ten experts with a research history on heat stress, including two professors, two associate professors, five assistant professors, and one Ph.D. candidate. They received an electronic mail, including the aims of the study and the draft questionnaire. The reviewers assessed the questions in terms of necessity using a 3-point Likert scale and in terms of relevance, clarify, and simplicity using the 4-point Likert scale. Lawshe and Waltz and Basel methods were applied to estimate the content validity ratio (CVR) and content validity index (CVI), respectively. The values of CVR and CVI greater than 0.79 and 0.62 were accepted, respectively , 22. TheFor evaluating the reliability, the revised draft questionnaire was completed by 200 staff occupied in warm and dry and warm and humid areas, detailed below. Observational questions were also filled out by researchers, as experts. After, coefficients of Cronbach\u2019s alpha (\u03b1) and McDonald\u2019s omega were calculated for all questions and each group of questions. Moreover, the item-total correlation (ITC) coefficient of each question was computed, and the questions with ITC less than 0.3 were omitted. The ITC refers to the correlation between the item and the total scale. The minimum acceptable value of \u03b1 was equal to 0.70 .After preparing the final questionnaire in the English language, a back-translation was performed. For this purpose, a blind translator was asked to translate the questionnaire back into the Persian language. Then, an expert panel, including two English language specialists, two Persian language specialists, and three occupational health specialists with a research history on heat stress, compared the original and translated versions of the questionnaire and examined any discrepancies. If applicable, the panel redrafted the questions and answers until their concept, meaning, and quality became the same.Two hundred Iranian male staff participated in the present study. It was tried that the subjects are selected from different industrial parts with a variety of climatic occupational conditions. For this purpose, the researchers attentively inspected the parts of these industries and elected the duties desired for performing the study. Then, the medical records of individuals working in these duties were investigated and the subjects with inclusion criteria were entered into the study. In the steel industry, these parts included forging, spark, induction melting, steelmaking, isolation, machining, refractory, technical support, engineering post, preventive maintenance, foundry, sandblast, metal waste separation, and administrative. In the petrochemical factory, the parts consisted of the warehouse, cookery, gardening, loading gantry, steel drum production, weighbridge, bitumen production, hydrocarbon, preventive maintenance, research and development, and administration. Inclusion criteria were career length higher than 1 year, no having mental, infectious, pulmonary, cardiovascular, hypertension, renal, hyperthyroidism, digestive, and diabetes diseases, non-use of medications to affect heart rate and blood pressure such as beta-blockers, phenothiazines, diuretics, anticholinergics, antispasmodics, psychotropics, antihistamines, antihypertensives, amphetamine, and decongestants, and non-use of coffee, caffeine, and alcohol from 12\u2009h before the study. Furthermore, their tympanic membrane and auditory canal were medically screened. Exclusion criteria included unwillingness to impressive cooperation and body temperature higher than 39\u2009\u00b0C during the activity.The aim of the present study was the development of an observational-perceptual index. The lowest correlation between the developed index and tympanic temperature was assumed as 0.2. Then, the sample size was computed based on the confidence level of 95% and a test power of 80% Eq. .1\\documeZ\u03b21\u2009\u2212\u2009 is equal to 0.84 for a test power of 80%, and W is equal to 0.203 for the lowest correlation coefficient of 0.2. Hence, the minimum sample size was obtained as 194 individuals.Where In this cross-sectional study, data were gathered in the spring and summer seasons of 2019. Firstly, the subjects were asked to rest on a bed in a cool place around their workplace for 30\u2009min. During this time, the steps of the study were explained to them and the demographical data of the subjects were collected. Also, their tympanic temperature was properly measured based on the standard of ISO 9886. After that, the participants were asked to return to their workplace and perform the routine tasks for 90\u2009min. The researchers completed the observational questions during this time. At the end of 90\u2009min, the tympanic temperature of the subjects was immediately and accurately measured based on the standard of ISO 9886. Simultaneously, they were asked to answer the descriptive and perceptual questions in the questionnaire. Moreover, environmental climatic parameters of dry temperature, wet temperature, globe temperature, relative humidity, and air velocity were recorded based on standards of ISO 7243 and ISO 7726. In the steel industry, the tasks performed by participants included refractory installation, metal waste separating, painting, welding, cutting, building, overhead crane operatory, overhead crane controlling, excavator driving, forklift driving, furnace operatory, casting operatory, pot operatory, sandblasting, molding, administrative activities, managing, monitoring, repairing, isolation operatory, and metalworking. In the petrochemical factory, the tasks performed by subjects consisted of cookery, cleaning, loading operatory, gardening, bitumen production operatory, hydrocarbon production operatory, drum carrying, welding, cutting, painting, pressing, administrative activities, managing, monitoring, forklift driving, repairing, building, and warehousing.The thermometer of Braun (IRT 6530 model with an accuracy of 0.1\u2009\u00b0C) was used to measure the tympanic temperature. The WBGT meter (TES 1369B model with an accuracy of 0.1\u2009\u00b0C) was applied for measuring the environmental climatic parameters of dry temperature, wet temperature, globe temperature, and relative humidity. Moreover, the developed questionnaire of OPHSRA was exploited to subjectively evaluate the effective items in producing heat strain through observation, description, and perception.The indirect effect coefficients of the items on thermal strain (variations of tympanic temperature) were calculated by structural equation modeling (SEM). Each of these coefficients was multiplied by the score of the related item, and resultant values were summed together for calculating the total score of the novel index.Gathered data were analyzed by the software of statistical package for the social sciences (SPSS) version 18. The normality of variables was examined using skew and kurtosis curves. Based on the results, all items had the normal distribution. Structural equation modeling (SEM) was applied to calculate the effect coefficients of the items. At first, the factor loadings of items of each factor, as direct effect coefficient, were computed using the Varimax method. Then, the regression method was used to calculate the score of each factor, in which factor loadings were multiplied by the data of each item. Later, a theoretical model was drawn using computed scores of the factors in AMOS software. The fitness of the designed model was evaluated using fit indices. Then, the novel index was developed by the indirect effect coefficients of the items in the model. Also, given the relationships between some of the items, it may be redundancy between them. In AMOS, modification Indices identified these redundant items. Co-variation was done between the measurement errors of redundant items based on the suggestion of the software for constraining the redundancy effects and increasing the fitness of the model. Finally, receiver operator curves (ROC) analysis was applied for categorizing the score of the novel index. Boundaries of risk levels included tympanic temperatures of 37.5, 38.0, and 38.5\u2009\u00b0C . In ROC In total, 36 proper items affecting the heat strain were identified and classified into six groups. Those included personal items of skin color, body resistance, and effective diseases, environmental items of air temperature, air humidity, radiant temperature, thermal conduction, air velocity, wind direction, air pollution, and noise, job items of physical activity, mental workload, body movement, and body posture, administrative items of heat adaptation planning, heat exposure duration, work-rest cycle, shift work, work location (indoor or outdoor), heat control measures, access to cooling facilities, and access to cool rest room, clothing items of material, size, weave, thickness, color, ventilation, type (underwear use and covered body surface area), and personal protective equipment, and lifestyles items of smoking, salt consumption, drinking water, sleep situation, and work experience in a warm environment. Then, a draft questionnaire was designed for assessing these items.In examining content validity, six items were eliminated, and 14 questions were revised. Furthermore, 14 items were omitted after evaluating the reliability of the questionnaire. The list of removed items is available in Table This study results from a field survey involving 111 male employees of a steel factory (hot-dry ambiance) and 90 of a petrochemical factory (hot-humid environment). The values of the mean (standard deviation) of age, height, and weight were equal to 36.62 8.24) years, and 1.76 (0.06) meters, and 80.52 (14.91) kilograms, respectively. Table\u00a0 years, aOPHSRA index was developed by the indirect effect coefficients of the items, as follow:Where Q1 to Q16 are the scores of the questions in the final questionnaire . It is ip\u2009<\u2009\u00a00.001), 0.915 (p\u2009<\u2009\u00a00.001), and 0.890 (p\u2009<\u20090.001), respectively. Moreover, the validity of OPHSRA was investigated using the linear regression analysis between the developed index and tympanic temperature. Figure\u00a0Figure\u00a0In the present study, 37 effective items in producing thermal strain were identified and categorized into six groups, including personal, environmental, job, administrative, clothing, and lifestyle items. Zheng et al. identified ten items and classified them into three groups, including work, environment, and worker, for evaluating the safety under hot and humid conditions . McLellaThis study was performed in the various climatic and occupational conditions so that the results revealed that the extensive ranges of scores related to observational, descriptive, and perceptual questions with normal distribution were collected. Therefore, this index can be applied for assessing the qualitative thermal strain risk of people occupied in different environments. In the model of the present study, environmental, administrative, job, and clothing items had significant effects on the thermal strain, respectively. Of these factors, the highest impact was related to the environmental items. In total, the main five items, including conductive heat, convective heat, radiant heat, sweat evaporation, and metabolism, impress on heat storage in the human body . TherefoBased on the results, the fitness of the presented model was confirmed, and the diagnostic accuracies of ROC curves were at acceptable levels. Furthermore, the validity of the developed index was investigated using linear regression analysis. The results indicated that the OPHSRA index could justify 69% of the variations of tympanic temperature. In the study of Dehghan et al. , this vaIn total, the results of the present study showed that the designed observational perceptual questionnaire had acceptable validity and reliability. This questionnaire evaluates the environmental, job, administrative, and clothing items using 16 items. Based on the results, the novel index developed by this questionnaire showed an acceptable validity in the prediction of thermal strain. Therefore, this index can be used for estimating the risk of thermal strain and preventing the occurrence of heat-related illnesses in a variety of thermal conditions. However, it is suggested that validation of this index is investigated in other industries and the female workers. Its validity can also be studied in non-work environments."} +{"text": "Streptococcus pneumoniae and Neisseria meningitidis remained at a stable level in all analyzed countries. Conclusion: Vaccine schedules differ among the countries, so does the epidemiological situation of selected diseases. Morbidity on measles was the most disturbing phenomenon: the incidence rate increased in almost 40% of all countries, regardless of the obligation to vaccinate. The increasing incidence of VPCD may be due to anti-vaccine movements, the activity of which is often caused by mistrust and spreading misinformation. In order to better prevent the increase in morbidity, standardization of vaccine schedules and documentation should be considered in the EU countries.Introduction: Despite the widespread availability of vaccines, the incidence of vaccine-preventable childhood diseases (VPCD) started to grow in recent years. The aim of the study was to compare the annual incidence of selected VPCDs in the EU (European Union) and EFTA (European Free Trade Association) countries in the period of the last 5 years , and the country-specific vaccine schedules. Methods: VPCD incidence rates in Europe were based on \u201cThe Surveillance Atlas of Infectious Diseases\u201d by the ECDC (European Centre for Disease Prevention and Control); vaccination schedules were based on ECDC reports. Results: The obligation to vaccinate was not universal, and it generally only applied to two preparations: the MMR vaccine and the one against polio. During the study, the situation associated with mumps did not change or improve in individual countries; the median incidence amounted to 30 cases. The median incidence associated with rubella amounted to 1 case, but in a few countries, it grew very rapidly, i.e., in Germany, Italy, and Romania; in Poland, the incidence was clearly decreasing, from 5923 to 1532 cases. The most dynamic situation concerned measles. The total median was 2.4 cases per 100,000 population; the only one country with falling incidence was Germany. The diseases associated with The introduction of vaccines against measles, rubella, mumps, polio, chicken pox, rotavirus diarrhea, as well as meningococcal and pneumococcal infections , bore the greatest importance in reducing infant and child mortality . UnfortuThe evidence on the effectiveness of vaccination and its importance for public health is the eradication of smallpox and the almost complete eradication of polio. In the early 1950s, polio epidemics caused paralysis in over 15,000 people in the USA alone. Following the introduction of the trivalent inactivated vaccine (IPV) in 1955 and the oral vaccine (OPV) in 1963, the number of cases of polio in the USA plummeted to fewer than 100 in the 1960s and fewer than 10 in the 1970s [Nevertheless, modern medicine is still struggling with VPCD, and the World Health Organization (WHO) has raised the alarm that some of them have again become a real threat to the health and life of newborns and children in all WHO regions . The objThe analysis encompassed the EU , Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Republic of Ireland, Romania, Slovakia, Slovenia, Spain, Sweden, and the United Kingdom (UK)) and EFTA countries . The years selected for analysis were 2014\u20132019 , excluding 2020 when the COVID-19 (coronavirus disease\u20142019) pandemic broke out, and a reduction in the vaccination coverage and decline in the total number of vaccines administered were observed worldwide .For our analysis, we have chosen a few viral and bacterial acute diseases with high epidemic potential, qualifying acute diseases as developing suddenly and lasting a short time, often only a few days or weeks, and accompanied by distinct symptoms that require urgent or short-term care. The analysis covered measles, rubella, mumps, polio, chickenpox, rotavirus, and bacterial: invasive meningococcal and pneumococcal infections. Data were collected and compiled on the basis of:Based on \u201cThe Surveillance Atlas of Infectious Diseases\u201d by the ECDC (European Centre for Disease Prevention and Control), the information contained in the dataset provided through ATLAS is made available by ECDC collating data from the Member States collected through The European Surveillance System (TESSy) ,9.https://www.ecdc.europa.eu/en/publications-data/data-national-14-day-notification-rate-COVID-19) (access on 30 June 2021)Converted the incidence for rubella, mumps, Streptococcus pneumoniae (Belgium only) into cases per 100,000 population; the populations were estimated based on a recent ECDC report , polio, chicken pox, and rotavirus diarrhea. Depending on the disease, the data for different years were available: 2015\u20132019 for measles, 2014\u20132018 for mumps, 2014\u20132019 for rubella, 2014\u20132018 for Streptococcus pneumoniae, and 2014\u20132017 for Neisseria meningitidis. For each disease and country, the infection cases from the available years were summed up and then presented as the number of cases in the period per 100,000 population.For rubella as well as meningococcal and pneumococcal infections, the total amounts of reported cases were summed up for each countryLong-term VPCD incidence rates were obtVPCD Incidence Rates in Europe:Due to the lack of data on the national incidence, the incidence rates of chickenpox and rotavirus were not analyzed . No dataBased on shared databases, ECDC reports .Vaccine schedule in Switzerland .Vaccination Schedules for Measles, Mumps, Rubella Polio, as Well as Meningococcal and Pneumococcal Infections:p < 0.05 was considered statistically significant.To compare the mandatory vs. non-mandatory policy to the annual incidence observed we used a generalized linear regression model. Calculations were performed using Statistica 13.3 . The incidence associated with the discussed infectious diseases varied greatly with no evident pattern or clear trend. Among the countries under study, only in Luxembourg and in Malta, the incidence rates observed for each of the diseases under study were low. In Austria, Belgium, Croatia, Cyprus, Denmark, Estonia, Hungary, Latvia, the Netherlands, Norway, Portugal, Slovakia, Slovenia, and Sweden, the situation was stable. In France, Italy, Germany (excluding measles), Romania, and the UK (excluding rubella), high incidence persisted .The most dynamic situation concerned measles. The median was 2.4 cases per 100,000 population, and the only one country with falling incidence was Germany: in 2015 it was 246, and there were 51 cases per 100,000 population in 2019. In half of the studied countries, increased incidence was found: in Bulgaria, Czechia, France, Slovakia, Slovenia, Spain, and the UK, where the increase was multiplied, and in Italy, Lithuania, Poland, and Romania, where the increase was bigger. The highest change in incidence was found in Italy, from 25.6 to 162 cases per 100,000 population, and in Bulgaria, with 0 and 111.9 cases per 100,000 population . The higDuring the study, the situation associated with mumps did not change or improve in individual countries. High incidence rates were constantly observed in Belgium, Czechia, Finland, Germany, Italy, Poland, and the Republic of Ireland. There has been a decline in Slovakia , and growth in Spain . The 5-yThe median incidence associated with rubella amounted to below 1 case per 100,000 population, but in a few countries, it grew rapidly, i.e., in Italy and Romania. In Poland, the incidence was clearly decreasing, from 15.6 to 4.0 cases per 100,000 population , but theAccording to ECDC data, Europe has remained polio-free since 2002 .Streptococcus pneumoniae and Neisseria meningitidis remained at a stable level in all the studied countries; however, this level was different. The highest was in Belgium, Denmark, Finland, Netherland, and Sweden (S. pneumoniae) and in Lithuania (N. meningitidis) and the Netherlands . The 5-yherlands . AccordiS. pneumoniae, and N. meningitides infections in studied countries.We found no simple correlation between mandatory vs. non-mandatory policy and the observed incidence of measles, mumps, rubella, N. meningitidis, Rotavirus and Varicella-Zoster Virus, were mandatory, while in 19 of the countries under study there was no compulsion in this regard. In Latvia, all vaccinations were mandatory except for N. meningitidis and the one against polio) and only to a limited extent. Countries with the highest numbers of mandatory vaccinations were in Bulgaria, Croatia, France, Hungary, Latvia, Poland, and Slovakia, where all of the discussed vaccines, except for the vaccinations against ngitidis .The most common vaccination was the one against polio, which was mandatory in 11 out of 31 countries: Belgium, Bulgaria, Croatia, Czechia, France, Hungary, Italy, Poland, Slovakia, Slovenia, and Malta. The MMR vaccine, against measles, mumps, and rubella, was mandatory in 9 out of 31 countries, both inside and outside the EU, namely, in Bulgaria, Croatia, Czechia, France, Hungary, Italy, Poland, Slovakia, and Slovenia .The pneumococcal vaccination was mandatory in 7 out of 31 countries . Meanwhile, the meningococcal vaccination was only imposed in France, and all 31 countries recommended these vaccinations .The MMR vaccination, against measles, mumps, and rubella, was administered in all 31 countries and in France; additionally, monovalent vaccines against measles, mumps, and rubella were used in 6-month-old children in specific circumstances. Vaccination with two doses of MMR was mandatory in all countries, and additionally, in Germany, Czechia, and France, it was possible to re-vaccinate a child at a later age if a dose had been omitted before. In 18 out of 31 countries, the first dose is given at 12 months . The earliest, one dose was routinely administered in Austria and Switzerland (9 months), in Denmark in risk groups (9 months), and in France in specific circumstances (6 months), while it was the latest in Sweden and Iceland (18 months) .As for the polio vaccine, the first dose was given to babies at 2 or 3 months of age, and only in Poland was it given only at the age of 4 months. The number of doses in different countries varies greatly. Currently, in two countries (Slovenia and Switzerland), three doses were administered. In 13 countries , four doses were administered, and Malta allows an additional, optional fifth dose. In 12 countries , five doses were applied, and Germany grants a sixth, non-mandatory dose. In three countries, there were six doses. In France, babies were given three doses, followed by booster vaccinations every 5 years. Inactivated polio vaccines (IPV) are employed in all countries studied and, in the UK, attenuated live vaccines (OPV) were additionally used. Currently, in Europe, the vaccines employed were designed to work solely against polio, and there were also combined vaccines against polio and other diseases .Pneumococcal vaccines were administered in all countries except for Estonia. The first dose was given at 2 or 3 months, whereas in Romania, the first dose was given only after the child turns 1 year of age. The majority of countries provided three doses, while Cyprus and the UK administer two doses .Meningococcal vaccination was carried out in 19 out of 31 countries (61.3%); however, they were mandatory only in France. Depending on the type of vaccine administered (against various serotypes), immunization schedules in different countries varied greatly regarding the number of doses administered. The MenB vaccine was administered in eight countries , and the number of doses in these countries ranged from one to four. MenC was administered in 14 countries, and there were usually one or two doses. MCV4 was administered in four countries , and there were usually 1\u20133 doses, depending on the country. In Switzerland, ACWY vaccine was administered for 2-year-olds, which constituted additional vaccination .Vaccination against rotavirus was conducted in 16 out of 31 countries, but they were mandatory only in Latvia and recommended in the remaining countries. Additionally, in Spain, the vaccination was recommended for babies born prematurely, and in the Netherlands to children from the exposed groups. The vaccination was not conducted in Bulgaria, Croatia, Cyprus, Denmark, France, Hungary, Iceland, Malta, Portugal, Romania, Slovakia, or Slovenia. Currently, all the countries mentioned make use of oral live attenuated vaccines. In five countries, vaccinations in children were started at 6 weeks , and in Poland between 6 weeks and 6 months. In 10 countries , children were vaccinated at 2 months of age, while in Italy from 3 to 7 months, and in the UK, it is performed at 8 weeks of age. The number of doses ranged from one to three, and usually, there were two doses .Varicella zoster virus was currently employed in 11 out of 31 countries, additionally in Poland and Czechia (for exposed groups) and in Belgium and Switzerland (only to people without immunity). In three countries , the vaccine was mandatory. The number of doses administered, depending on the country, amounted to one or two and countries bordering the EU, Ukraine, Bosnia, and Herzegovina, remain at high risk of a sustained polio outbreak .Old Union, Spain, France, or Italy. However, it is difficult to escape from the historical context, as the vaccination obligation applies mainly to the countries of the former Eastern Bloc: Bulgaria, Croatia, Hungary, Latvia, Poland and Slovakia, and, exceptionally, France. On the other hand, in Bulgaria, Czechia, France, Italy, Romania, and the UK, vaccination coverage was very low in 2018, less than 90%, and in Poland, Slovakia, Slovenia, Lithuania, and Spain, it was only slightly better, below 95% [The most disturbing situation concerns measles. Almost 40% of the countries studied report an increasing incidence of the disease, and this growth applies to countries where vaccination is mandatory, such as Bulgaria, Czechia, France, Italy, Poland, Slovakia, and Slovenia, as well as the ones where vaccinations are only recommended, such as Lithuania, Romania, Spain, and the UK. The situation also has no relation to the historical context, i.e., high incidence occurs in both countries of the former Eastern Bloc, among others, Lithuania, Poland, and Romania, as well as in the so-called elow 95% . We founelow 95% . FurtherMigration may be another reason for the wide variation regarding the measles incidence rate. For example, Italy\u2014where high incidence rates were reported for measles, mumps, and rubella\u2014is a country with a large number of foreign residents who arrive from outside the EU, including, among others, North Africa . UnfortuThe above elements, which could have an impact on the effectiveness of surveillance of the VPCD, do not explain the situation observed in Poland, where the 5-year incidence of rubella and mumps was several times higher than in the EU. It was also high in the closest EU neighbors\u2019 countries. This might also be caused by the relatively recent introduction of the MMR vaccine for all children in Poland (2004).Therefore, compliance with the vaccination schedules applied is perhaps important; however, vaccination schedules for measles, rubella, mumps, pneumococci, and meningococci in Europe and other countries studied are very similar, and relatively minute differences concern the schedule of administration of the preparations (ages at which subsequent doses are administered/number of doses) and reimbursement\u2014the level of co-payment for the vaccine and its administration and the obligation or voluntary administration of the vaccine\u2014which is especially true of pneumococcal and meningococcal vaccines.Neisseria meningitidis, was characterized by a great diversity throughout the European Union, possibly related to the high variability of their serotypes, which additionally vary in different populations. In Europe, invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae, is one of the main causes of meningitis or invasive inflammatory diseases of various organs in children and community-acquired pneumonia in adults. Currently, the number of serotypes of these bacteria is estimated at over 90, which implies enormous problems in the practical application of the available vaccines [S. pneumoniae serotype in Denmark [S. pneumoniae isolates in Sweden are contained in the PCV13 vaccine [The epidemiology of two diseases caused by encapsulated bacteria, Streptococcus pneumoniae and vaccines . The thrvaccines . Serotyp Denmark . Only 17 vaccine .S. pneumoniae cases has been a significant problem in Slovenia for many years. National Vaccine Recommendations Program against S. pneumoniae was introduced in 2015, but vaccination coverage is still moderate (49\u201355%). Unfortunately, in addition, there is an increased number of cases caused by penicillin-resistant strains, possibly due to the overuse of antibiotics [A high number of ibiotics .Neisseria meningitidis, causing invasive meningococcal disease (IMD), has 13 serotypes. Serotype A is responsible for the majority of the illnesses, and it is also accountable for cyclical epidemics of meningitis in North Africa every 5\u201310 years and, in the past 25 years, in China and Russia. Serotype A was also responsible for individual IMD outbreaks in Europe until the mid-twentieth century. Diseases caused by serotype B are rarer; however, its long-term outbreaks are characterized by high morbidity and mortality [ortality . At the ortality . Accordiortality .It is estimated that socioeconomic factors determine the health of the population to the extent of 40% in the USA , and alsThe anti-vaccine movement is not a new phenomenon. As early as the late nineteenth century, there were protests in the UK and the USA against the mandatory smallpox vaccination, arguing that mandatory vaccination was a violation of the right to take care of one\u2019s body in any way one choose .At times, the reason for fear and aversion to vaccinations lay in political decisions; however, the contemporary reason for the lack of trust in vaccination may also be the shortcomings of the procedures concerning controlling scientific integrity, associated with the publication by Andrew Wakefield falsifying the relationship between MMR vaccine and autism as well as enteritis in children. It was when one of the biggest myths regarding vaccination was born, which has been constantly reproduced since its inception in 1998 and fervently cited in discussions, despite the fact that the publication was later withdrawn and debunked repeatedly. The Global Advisory Committee on Vaccine Safety found no link between the vaccine and autism spectrum disorder. The publication of Wakefield\u2019s article caused a long-standing health crisis. The Lancet published an apology and evidence that the study was based on false data. Andrew Wakefield was found guilty of violating professional ethics and removed from the British Medical Register. Even though the myth has long been refuted, distrust of vaccination has begun to spread around the world. Opponents of vaccination, despite the evidence and indisputable facts, continue to use Wakefield\u2019s conclusions in their anti-vaccination campaigns .Anti-vaccination movements make use of modern channels of communication, such as social media, and, since 2019, social media accounts run by Vaccine-Hesitant Men (or anti-vax) are followed by at least 7.8 million more people than before . AccordiSocial attitudes towards vaccination can be divided into three categories: there are people who are vaccinated willingly (in the UK and the USA: 70\u201390% of the population), dogmatic opponents of vaccination who will not change their views, and undecided people who ask valid questions, and it is this group of people that should be focused on, educated, and informed .Catalogue of interventions addressing vaccine hesitancy, a practical tool for public health organizations and immunization stakeholders [The anti-vaccine movement is perhaps one of the reasons for the growing incidence of measles. ECDC recognized the seriousness of the problem and prepared a document entitled eholders .It should be considered to standardize the calendars and documentation confirming vaccinations at the EU level, which is especially vital in the time of the COVID-19 pandemic. The electronic version of such a document would allow access to information concerning past vaccinations, both for EU citizens traveling within the EU, as well as for newly arrived immigrants.Moreover, the situation in Poland and in Lithuania (N. meningitidis) indicates that the response of the epidemiology of VPCD to any changes in vaccination is a long-term one. This is a public health component that takes time to show, and the situation can only improve after many years of intensive work on an effective vaccination schedule. The epidemiological situation of Finland, Sweden, Norway, Denmark, and the Netherlands (IPD) proves the importance of an appropriate selection of serotypes for vaccine production."} +{"text": "African Journal of Disability 9(0), a669. https://doi.org/10.4102/ajod.v9i0.669, the author\u2019s affiliation was given incorrectly in the \u2018Affiliation\u2019 section. The correct affiliation should be \u2018School of the Arts, Faculty of Humanities, University of Pretoria, Pretoria, South Africa\u2019 instead of \u2018School of Visual Arts, Faculty of Humanities, University of Pretoria, Pretoria, South Africa\u2019.In the version of this article initially published, Du Plessis, R., 2020, \u2018The life stories and experiences of the children admitted to the Institute for Imbecile Children from 1895 to 1913\u2019, This correction does not alter the significance of the study findings or the overall interpretation of the study results. The publisher apologises for any inconvenience caused."} +{"text": "The quick spread of invasive arthropod species worldwide, sometimes boosted by global warming and urbanization ,2,3,4, oEucalyptus citriodora and the related molecule p-menthane-3,8-diol) [Further, bites from bloodsucker insects and mites can be avoided using repellents. In this scenario, discovering novel and effective products to repel mosquitoes, ticks and tabanids, just to cite some hot examples, is a challenge for public health ,12,13,14,8-diol) .In this framework, the present Special Issue is dedicated to the development of effective and eco-friendly insecticides, acaricides, repellents and antimicrobials, including products of natural origin . Research efforts shedding light on the modes of action, behavioural modifications and non-target effects of the above-mentioned natural products have been welcomed. It has been recommended to the authors to include a positive control in the experiments , as well(a)Laboratory evaluation of the insecticidal, acaricidal and/or antimicrobial activity of plant essential oils ,19.(b)Isolation of pure constituents from plant extracts, and assessment of their insecticidal ,21,22, a(c)Synthesis and characterization of novel semisynthetic insecticides, along with their in vitro evaluation on insect cells .(d)Exploitation of invasive plant species as sources of effective insecticidal products .(e)Evaluation of the impact of selected plant-borne compounds on the behaviour of key insect pests, with special reference to aphids .(f)Development of botanical-based insecticidal formulations (including nanoformulations) characterized by an improved bioactivity and stability over time ,30.Herein, contributions on the following topics have been included:Finally, the Special Issue ends with two reviews. The first summarized current knowledge on the use of diatomaceous earths in crop protection, stored product, and urban pest control, presenting a number of challenges for future research . The secIn conclusion, despite the relevant research efforts undertaken in this field for discovering new insecticides, acaricides and repellents of natural origin, the road to their large-scale use in the real world appears long and windy, complicated by costly and complex authorization requirements , and wit"} +{"text": "In the published article, there was an error in affiliation 4. Instead of \u201cDepartment of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China\u201d, it should be \u201cDepartment of TCM Oncology, Putuo District Central Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The aim of this article is to present results of theoretical study on the properties of C\u22efM bonds, where C is either a carbene or carbodiphosphorane carbon atom and M is an acidic center of MX Crystals [Undoubtedly, one can get an impression that there has been a kind of race that has been going on for over a dozen years related to the introduction of various names for various interatomic contacts. The current situation with this nomenclature has recently been well captured by Alkorta, Elguero, and Frontera in a review article in Crystals . Thus, iCrystals ,14,15,16Crystals ,20,21,22Crystals ,32,33,34Crystals ,44,45,46Crystals ,53,54,55Crystals ,61,62,63Crystals ,70,71,72Crystals ,76,77,78Crystals ,80,81. ACrystals ,18,19,20Crystals ,28,29,30Crystals ,32,33, aCrystals ,88,89,90Crystals ,92,93. UDue to their specific electronic structure, carbenes occupy particular position in organic chemistry ,102,103. singlet Figure R2 covalep orbitals and have the same spins. In the singlet state, both electrons form a lone pair on one of the perpendicular p orbitals. Due to the presence of the often readily available electron lone pair, carbenes in the singlet state are good Lewis bases; i.e., they feature strong nucleophilic properties. Indeed, the nucleophilic properties of carbenes are well known and are often used in organic and organometallic synthesis [In the triplet spin state, both electrons occupy perpendicular ynthesis ,102,103.ynthesis ,110,111,ynthesis ,113,114,ynthesis ,117,118,ynthesis ,120,121,ynthesis ,124,125,ynthesis ,127,128,ynthesis ,130,131,ynthesis , halogenynthesis ,135,136 ynthesis ,134), anynthesis . Moreoveynthesis ,138,139,ynthesis ,102,139.ynthesis ,121, arep orbital perpendicular to the plane of the molecule, leading to the electrophilic properties of a given carbene [p orbital on the carbene carbon atom of singlet carbenes [ carbene ,144,145. carbene . A practcarbenes . It is wcarbenes ,144,145.p orbital on the carbene carbon atom and their amine analogues ,171,172.It is understandable that so far, the vast majority of theoretical studies on beryllium and magnesium bonds have used as Lewis bases small molecules containing either some atoms with good electron-donating properties or \u03c0 bonds ,30,31,32\u03c0 bonds ,92,93, e\u03c0 bonds ,93. It iIn order to unite these two thematic areas, this article describes the result of theoretical research on a large group of dimers with a beryllium bond, magnesium bond, or zinc bond between various Lewis acids of the MXium bond with theAs mentioned in the Introduction, this article describes research on systems containing a beryllium bond, a magnesium bond or a zinc bond, where the role of Lewis acids is played by the MXMeXsp orbital of the metal atom with one of the orbitals of X. Due to lower electronegativity of the metal atom, this atom is endowed with a partial positive charge does not, suggests that q(M). Although the linear relationship between the value of q(M) is computed utilizing the Hirshfeld method, it is much better than in the case of NBO- and especially QTAIM-based charges to 0.2 (blue)) for all MX (59 pm) . Therefo in MgF2 . The fac charges .Carbenes and CDPsImidazol-2-ylidene, imidazolidin-2-ylidene, tetrahydropyrymid-2-ylidene, cyclopropenylidene, and large variation in the negative values on the C atom in atom in the carbenes or the C(0) atom in the CDPs. On the other hand, strong positive potential concerns mainly hydrogen atoms in strongly polar N-H bonds. While the characteristics of the negative potential distribution around the carbon atom are similar in carbenes \u22efM interactions in the dimers formed by , which Very high bond strength of C(0)\u22efM in the is often treated as a measure of the strength of this interaction . If so, It should also be interesting to check the quality of the linear relationship between the values of The positive values of the Lell type . Howeverovalency . On the A very important QTAIM parameter often used to describe the A\u2013B bond strength is the s A and B ,183,184.strength . It is wThe quality of the obtained linear correlations clearly depends on both the correlated parameters and the type of the metal atom in the MX0.732 au , thus caMost of the QTAIM-based parameters are determined at critical points , and therefore these parameters are local, i.e., they provide information about the properties at a particular point in space. One way out of this limitation is the NCI method ,193, whiof atoms . In ordeg and Zn .not followed by the presence of the respective bond paths. It has been shown that the presence or absence of a bond path generally has little to do with the interaction strength [The subfigure (a3) shows that the zinc bond in the cyclopropenylidene\u22efZnBrstrength ,196,197.Summing up, it can be concluded that the analysis based on the NCI method shows that the zinc bond is the strongest, and although the beryllium bond should only be slightly weaker than it, the latter is related to the presence of additional areas of weaker interaction in the antibonding regions of the Be atom. The high strength of the C\u22efZn bond (competing even with the Zn-Br bond) is reflected in high values of Geometries of monomers and dimers were fully optimized on the nctional of Densinctional ,200,201 nctional ,205,206,en shown to be onen shown . NBO-basen shown ,181 atomen shown implemenen shown ,183,184 en shown methods en shown .To date, the vast majority of theoretical studies on beryllium and magnesium bonds have used as Lewis bases small molecules, and the research on zinc (spodium) bonds is very rare. On the other hand, the research on carbenes and carbodiphosphoranes is mostly experimental. This article presents the results of theoretical research on the properties of beryllium, magnesium, and zinc bonds in a large group of dimers formed by the MXThe general characteristics of the presented dimers showed that the dissociation energies of the C(2)\u22efM intermolecular interaction have wide range, from 10 to 53 kcal/mol, and this interaction is the strongest for the BeBrImportantly, it has been shown that the investigated systems are characterized by very high charge transfer effect from the carbene or carbodiphosphorane molecule to the MXTheoretical studies based on the QTAIM and NCI methods have shown that the zinc bond is not very different from the beryllium bond; both should be of similar strength, while the magnesium bond should be weaker. Both are also characterized by a high degree of covalence. The determined values of the delocalization index show, however, that the zinc bond should be definitely stronger than the beryllium and magnesium bonds.A large number of tested dimers as well as parameters characterizing both the interacting subsystems and the C\u22efM bond itself allowed for the study of many linear relationships between the parameters. In general, they are good as long as systems with different M metal atoms are treated separately. The linear correlations for the zinc atom are usually slightly better than for the other atoms.In addition to the dominant C\u22efM interaction, some of the studied dimers also have various additional interactions, such as, e.g., the N-H\u22efF, N-H\u22efC and F-H\u22efN hydrogen bonds, or N-H\u22efH-Mg dihydrogen bond. In the latter case, it may be extremely short, such as 1.44 \u00c5 in (NHA side result of the presented research is that the atomic charges obtained by the QTAIM method are highly unreliable. While more reliable than these, the NBO-based atomic charges also appear to be questionable. In contrast, the Hirshfeld atomic charges appear to be chemically sound."} +{"text": "Fresh and processed food products are rich in bioactive molecules, including polysaccharides, vitamins, carotenoids, peptides, antioxidants, phenolics, phytosterols, and novel lipids. Bioactive molecules in food could prevent several diseases . Thus, consumer awareness is growing about the health-promoting impact of food bioactive molecules. Health claims are essential added-value features, wherein health-enhancing potential of bioactives depend on their chemical structure. On the other hand, the investigation of the structure-function relationship of food bioactive molecules is of importance. In this regard, Molecules is delighted to highlight the importance of food bioactive molecules and their effect on health. In this Special Issue of Molecules, researchers are invited to contribute original research and up-to-date reviews. Fresh and processed food products are rich in bioactive molecules, including vitamins, carotenoids, polysaccharides, proteins, peptides, antioxidants, phenolic compounds, sterols, and bioactive lipids ,4,5,6,7.Consumer awareness is growing about the health-enhancing effects of food bioactive molecules from plant and animals sources. Health claims are important value-added features for consumers, wherein authorities accept health claims in functional foods based on scientific evidence. The health-promoting impacts of bioactive compounds depend on their chemical structure; therefore, novel analytical techniques have been developed to elucidate the structure of active molecules ,15,16,17To give a recent view of the interest raised in the international research context within this topic, a search throughout the Scopus database was carried out using a string TITLE-ABS-KEY . The search returned 87,471 documents covering the time range from 1884 to 2022. In the last ten years (from 2011\u20132020), the search returned 48,842 documents .Apart from the published documents, approx. 30,600 were research articles, 1160 conference papers, 10,500 reviews, and 2800 book chapters. The documents annually published on \u201cfood *\u201d, \u201chealth *\u201d, and \u201cdisease *\u201d are notably increased from 3537 contributions in 2011 to 7370 contributions in 2020. This measurable indicator reflects the importance and interest in \u201cfood *\u201d, \u201chealth *\u201d, and \u201cdisease *\u201d as a topic in the scientific community. The documents are related to the subject areas of Medicine, Agricultural and Biological Sciences, Biochemistry, Genetics, and Molecular Biology, Nursing, Immunology and Microbiology, Pharmacology, Toxicology, and Pharmaceutics, and Environmental Science. Scientists from the USA, UK, China, India, and Australia emerged as main authors.This Special Issue of Molecules is entitled Advances in Research on Food Bioactive Molecules and Health. In this regard, Molecules is delighted to highlight the importance of food bioactive molecules and their effect on health. Researchers from different fields, including food chemistry, biochemistry, natural products, phytotherapy, pharmacology, medicine, and biotechnology, are expected to disseminate their results in this issue. In this Special Issue of Molecules, researchers are invited to contribute original, unpublished research and up-to-date review articles that analyze and describe bioactive molecules in fresh and processed food products; their stability during food processing and storage; and the mechanisms of their digestion, bioactivity (in vitro and in vivo), and metabolite formation. In addition, the impact of food bioactive molecules in preventing and treating diseases is of interest.Potential topics include, but are not limited to, the following: (i) novel analytical techniques in the structure elucidation of food bioactive molecules; (ii) chemistry and functionality of food bioactive molecules; (iii) factors affecting the structure-function relationship of food bioactive molecules; (iv) the effect of industrial and biotechnological processing on food bioactive molecules; (v) modification of food bioactive molecules to enhance their health-promoting effects."} +{"text": "Food security and nutrition have been prominent elements of the international development agenda. Over time, however, development priorities and challenges have oscillated, and the investment required has not been sustained. A broader consensus has emerged: one that guarantees food security and, in all its aspects, reduces hunger and malnutrition to promote strong economies, human and planetary health, and sustainable development. Our moral imperative is to positively change food systems to ensure that the food we produce is accessible, sustainable, safe, healthy, and equitable for everyone. Therefore, this special issue about Food Systems and Nutritional and Food Security focuses on connecting the importance of food systems to change nutrition and food security around the globe.In this context, attitude and knowledge of health, food, and nutrition can be one of the keys to facing food insecurity in several countries. Health and nutritional education are imperative to fight malnutrition ,2,3,4. KAdequate and healthy diets imply choosing and consuming balanced and adequate foods on nutrients and amount, variety, and sustainable aspects. Therefore, achieving the main social, economic, environmental, cultural, and security goals ,14,15,16During these past two years of the COVID-19 pandemic, the world has faced new food security and safety challenges. Firstly, food sales worldwide became more complex, and farmers faced many overstocked products leading to food loss . On the"} +{"text": "The Positivity Workbook for Teens: Skills to Help You Increase Optimism, Resilience, and a Growth Mindset, the authors Goali Saedi Bocci and Ryan M. Niemiec deliver a self-improvement book for teens struggling with adolescence. The book is adapted from Martin Seligman's PERMATM model\u2014a leading theory in positive psychology\u2014which holds that flourishing is based on five pillars of well-being: positive emotions, engagement, relationships, meaning, and accomplishment . In Chapter 1, Identifying Positive Emotions, the reader reflects on the ten core positive emotions how negative affect and cognitions can be modified through adaptive coping and behavior; and (b) how problem behaviors can be modified through adaptive affect and cognitions. In Chapter 3, Forecasting Your Mood, the reader considers several upcoming life events, within the framework of past successes and past failures.Part 1, Happiness (Zest Booster!), the authors discuss hedonic (pleasure-based) and eudaimonic (meaning-based) routes to happiness. In Chapter 5, Optimism (Hope Booster!), the reader is introduced to several different framing styles associated with optimism and well-being. In Chapter 6, LOL and Live Fully (Humor Booster!), the authors tout the benefits of laughter in our lives . In Chapter 8, What Motivates You?, the authors focus on intrinsic motivation\u2014i.e., the undertaking of an activity for its inherent satisfaction and strengths specific to the heart . In Chapter 13, Overcoming Boredom, the authors promote curiosity as an antidote for boredom. The authors have the reader focus their attention. This act is core to mindfulness, a practice with numerous health benefits Tribe, draws on the strengths of love, kindness, and teamwork, and helps the reader nurture positive relationships (\u201cR\u201d of PERMATM). In Chapter 14, Next-Level Bully Management, the authors warn the reader to think before they act, and make decisions from a place of inner peace. In Chapter 15, Are You My Friend or Frenemy?, the authors advise the reader to nurture their deep friendships, and be generous in expressing gratitude.Part 3, Your Key Relationship Strengths, the authors discuss honesty, love, forgiveness, kindness, humility, fairness, social intelligence, and zest. The reader reflects on what changes they can make to cultivate these strengths, with respect to their relationships with others. In Chapter 17, Stop Comparing Yourself to Others!, the authors suggest (a) setting social media limits, (b) engaging in noncompetitive activities, (c) focusing on the future, (d) practicing gratitude, and (e) remembering your character strengths. In Chapter 18, Getting Off (or On) the Social Media Bandwagon, the authors beg the reader to go \u201cscroll-free\u201d for a week, and record their observations in a journal. In Chapter 19, Combatting Loneliness and Isolation, the authors prescribe caring and knowing as a cure for loneliness.In Chapter 16, Cultivating What Matters Most, draws on gratitude, appreciation of beauty, and social intelligence, to help the reader find more meaning in their life (\u201cM\u201d of PERMATM). In Chapter 20, Savor Special Moments with Family, the reader reflects on pleasant memories shared with family, and uses them as fuel to fuel the future. In Chapter 21, Build an Attitude of Gratitude, the authors have the reader write a letter to someone important in their life, and thank them for their support and influence. This practice\u2014expressive writing writes about three beautiful things they came across that day, (b) creates a portfolio of things that trigger inspiration, and (c) adds beauty to their personal environment . In Chapter 25, Cultivating Spirituality and the Sacred, the reader considers (a) the purpose of their life, (b) the meaning of spirituality, and (c) what connects them to the sacred in their life. Chapter 26, Overcoming Jealousy, Envy, and FOMO, is tailored for the teen that overloads themselves\u2014trying to keep up with their peers\u2014and is driven by the fear of missing out (FOMO).In Chapter 23, s Bluth, . In ChapYour Goals, Your Life, draws on perseverance, perspective, and zest, to help the teen along the path to their accomplishments (\u201cA\u201d of PERMATM). In Chapter 27, Your Best Possible Self, the teen envisions themselves one year in the future, having reached their full potential or a milestone. They ask themselves, What character strengths are needed to make this a reality? In Chapter 28, Hope for Your Goals, the teen picks a goal, and using pathways thinking, conceives several different routes to take them there. In Chapter 29, Taming Your Inner Critic, the authors introduce the teen to loving-kindness meditation, a practice potent in promoting positive emotions (Fredrickson et al., Part 5, Healthy Body, Healthy Mind, taps self-regulation, prudence, and perseverance, to link a healthy body to a healthy mind. In Chapter 30, Promoting Good Health, the authors introduce the Five Pillars of Good Health (Niemiec, Part 6, Niemiec, : exercisThe Positivity Workbook for Teens is a self-improvement book for teens struggling in the throes of adolescence. It is grounded in the teachings of positive psychology (Seligman, TM structure offers a sound foothold. In sum, The Positivity Workbook for Teens is an engaging self-help program for teens, their families, and their counselors.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In \u201cCommunity Mitigation of COVID-19 and Portrayal of Testing on TikTok: Descriptive Study\u201d :e29528), one error was noted.Due to a system error, the name of one author, Hao Tang, was replaced with the name of another author on the paper, Alessia Pellicane. In the originally published paper, the order of authors was listed as follows:Corey H Basch, Jan Mohlman, Joseph Fera, Alessia Pellicane, Alessia Pellicane, Charles E BaschThis has been corrected to:Corey H Basch, Jan Mohlman, Joseph Fera, Hao Tang, Alessia Pellicane, Charles E BaschIn the originally published paper, the ORCID of author Hao Tang was incorrectly published as follows:0000-0002-8220-6584This has been corrected to:0000-0003-3002-1374The correction will appear in the online version of the paper on the JMIR Publications website on June 29, 2021, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "In the published article, the affiliations of the author Bach Xuan Tran is not correct. Instead of having affiliations \u201cInstitute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam\u201d and \u201cBloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA\u201d, they should have \u201cInstitute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam\u201d and \u201cBloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In the published article, there was an error in affiliation 6 and 8. Instead of \u201cDepartment of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia.\u201d it should be \u201cDepartment of Medical Microbiology, Universiti Putra Malaysia, Serdang, Malaysia.\u201d And \u201cDepartment of Biotechnology, Bharath Institute of Higher Education and Research, Chennai India.\u201d should be \u201cCentre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, India.\u201dIn the published article, there was an error regarding the affiliation for Avin Ee-Hwan Koh. The correct affiliations should be \u201cDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.\u201d And \u201cDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In the published article, an author name was incorrectly written as \u201cCherdsak Duang.\u201d The correct spelling is \u201cCherdsak Duangchan.\u201dIn the published article, there was an error in affiliation 1. Instead of \u201cCollege of Nursing, The University of Illinois Chicago, Chicago, IL, United States\u201d it should be \u201cCollege of Nursing, University of Illinois at Chicago, Chicago, IL, United States.\u201dIn the published article, there was an error in affiliation 2. Instead of \u201cUniversity of Illinois Cancer Center, The University of Illinois Chicago, Chicago, IL, United States\u201d it should be \u201cUniversity of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States.\u201dIn the published article, there was an error in affiliation 3. Instead of \u201cSchool of Public Health, The University of Illinois Chicago, Chicago, IL, United States\u201d, it should be \u201cSchool of Public Health, University of Illinois at Chicago, Chicago, IL, United States.\u201dThe authors apologize for these errors and affirm that they do not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Bilal U, Alazraqui M, Caiaffa WT, et al. Inequalities in life expectancy in six large Latin American cities from the SALURBAL study: an ecological analysis. Lancet Planet Health 2019; 3: e503\u201310\u2014In this Article, due to a linkage error with the Panama City data, life expectancy data, P90\u2013P10 gaps, and associations with education have been corrected for Panama City in the Summary, table 2, the Results, where appropriate in the Discussion, in figures 1 and 2, and in the appendix. Additionally, support from the SALURBAL investigators has been added to the Acknowledgments section. These corrections have been made as of Jan 3, 2020."} +{"text": "In the published article, there was an error in the order of the authors in the author list. Instead of \u201cAnna Kostera-Pruszczyk, Anna Potulska-Chromik, Ma\u0142gorzata \u0141ukawska, Marta Lipowska, Dorota Hoffman-Zacharska, Beata Olchowik, Magdalena Figlerowicz, Karolina Kanabus and Edyta Rosiak,\u201d it should be \u201cMa\u0142gorzata \u0141ukawska, Anna Potulska-Chromik, Marta Lipowska, Dorota Hoffman-Zacharska, Beata Olchowik, Magdalena Figlerowicz, Karolina Kanabus, Edyta Rosiak and Anna Kostera-Pruszczyk.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Luigi Orsenigo passed away in May 2018, leaving all of us with a major loss. This special issue in his honour brings several contributions in the areas in which Gigi contributed in a significant way in the course of his career: the pharmaceutical and biotechnology industries, innovation and industrial dynamics, evolutionary theory and modelling.After graduating in Economics at Bocconi University, Luigi obtained a Ph.D. from the Science Policy Research Unit (SPRU), University of Sussex. Over the course of his career, he has been affiliated with Bocconi University, the University of Brescia and the Open University. At the moment of his death, Luigi Orsenigo was R.M. Phillips Professor of Economics of Innovation at SPRU and Professor of Applied Economics at IUSS (Institute for Advanced Studies) at Pavia. He had also been Fellow of Cespri first, and ICRIOS later, both at Bocconi University. For a long time, he has served as Editor of the Journal of Evolutionary Economics, Advisory Editor of Research Policy and Associate Editor of Industrial and Corporate Change, the main journals devoted to economics of innovation and industrial change. He also has been advising several Italian and international institutions on matters of innovation and industrial policy, including the European Commission and the World Intellectual Property Organization (WIPO).Luigi has been the author of four books and has published many articles on major international journals. The bibliography at the end of this introduction includes his main contributions. In 2012, he has been awarded the Schumpeter Prize for the book \u201cInnovation and the Evolution of Industries. History Friendly Models\u201d, together with F. Malerba, R. Nelson and S. Winter, Cambridge University Press.in this Special Issue reconstructs Luigi\u2019s intellectual development and also provides personal memories.Since his graduation from SPRU Luigi has consistently developed a series of lines of research that have span over a set of areas that are broad but interconnected. One of us, Franco Malerba, In this Special Issue we want to honour Luigi\u2019s memory with contributions that are related to his research. The papers are written by some of the key co-authors of Orsenigo and reflect his main areas of research.file rouge during his life, concerns innovation and the evolution of the pharmaceutical and biotechnology industries, with the role of science playing a prominent role. Among the many papers and book written by Luigi on this topic, here we want to mention \u201cThe Emergence of Biotechnology. Institutions and Markets in Industrial Innovation\u201d, Pinter Publishers, London, 1989; \u201cTechnological Change and the Dynamics of Networks of Collaborative Relations. The Case of the Bio-pharmaceutical Industry\u201d, (with F. Pammolli and M. Riccaboni), Research Policy, 2001; \u201cThe Economics of Biotechnology\u201d, , Edward Elgar, Cheltenham, 2006.A first area of major research by Luigi Orsenigo, a real Luigi has been interested in the biotechnology revolution and the changes that have consequently occurred in the pharmaceutical industry. Due to this revolution, an industry dominated by a stable core of large firms moved to a market structure in which a division of scientific, innovative and production labour has taken place between large incumbent firms and innovative start-ups. This major change and the evolution that followed is also related to a new role that science has taken place in the pharmaceutical industry and to the new relevance of universities and university spin-offs. This new scientific knowledge base changed the type of competition among large incumbents and entrants and led to the rise of networks of collaborations in R&D among actors of different types. Luigi also examined the changes in the industry in the most recent period, in which some of the new entrants have become also integrated pharmaceutical companies, while at the same time some of the large pharmaceutical companies developed their own in-house capabilities in science and biotechnology. In all these dynamics, the high appropriability conditions that characterize the pharmaceutical industry, in which patents play a major role, have fostered and also limited technological change, competition and economic development, in various and complex ways.Exploring Network Dynamics in Complex Fields of Science: The Formation of Ties to Knowledge Translatorsstart from Luigi\u2019s interest in the analysis of the relationship between individual scientists, knowledge evolution and the structure of the pharmaceutical industry. In a sample of 9543 cancer clinical trials over the period 2002\u20132012 they examine how changes in networks are influenced by the structure of networks as well as the behaviours and characteristics of key individual scientists. Using temporal exponential random graph models, they examine whether the mechanisms of preferential attachment, multi-connectivity, and homophily drive the formation of new collaborative relations to investigators who have knowledge in basic and clinical research. Results indicate that, first, the fragmentation of the network remains high, due to a considerably increasing number of investigators in the network and, secondly, that this fragmentation limits opportunities for knowledge transfer. Homophily in research fields and country of investigators\u2019 affiliation as well as heterophily in terms of publication output are drivers for tie formation to these knowledge translators.Two papers in this Special Issue focus on the pharmaceutical industry and on the role of scientists and R&D and knowledge networks. Bastian Rake, Pablo D\u2019Este and Maureen McKelvey in The Network Origins of Schumpeterian Innovation investigate the evolving division of innovative labour in biotechnology and pharmaceuticals from 1981 to 2012, with particular reference to the roles of large and small firms. Relying on topological methods they find that, while a regime of polarization through preferential attachment driven by large pharmaceutical companies dominated the early stages of the biotechnology revolution, in recent years the evolution of the collaborative network has been shaped by roles\u2019 transitions between originators and developers of innovative ideas. In particular, starting from the early 2000s, the emergence of general purpose research technologies and the scientific and technological transformations in genomics have led to a promiscuity of roles, as small and large firms act both as originators and developers, in a less polarized network. The authors then propose a parsimonious model of network formation and evolution able to account for some of the features of the processes underlying the evolution of the network.Fabio Pammolli, Massimo Riccaboni and Alessandro Spelta in Cambridge Journal of Economics, 1995; \u201cTechnological Regimes and Sectoral Patterns of Innovative Activities\u201d , Industrial and Corporate Change,1997 and \u201cTechnological regimes and Schumpeterian patterns of innovation\u201d , The Economic Journal, April, 2000. In these and other contributions the view that the specific properties of the technology of an industry in terms of opportunity, appropriability and cumulativeness conditions and of the knowledge base affect the industrial patterns of innovation is proposed. In particular, a technological regime in which opportunity conditions are high, the appropriability of innovation is low and the cumulativeness of innovation lead to a sectoral pattern supportive to new firms, turbulent industrial dynamics and a changing hierarchy of major innovators (Schumpeter Mark I); on the contrary, a technological regime characterized by medium or high technological opportunities, high appropriability and cumulativeness are conducive to a more stable and concentrated industrial pattern of innovation (Schumpeter Mark II). These relationships have been discussed at the theoretical level and in several contributions tested empirically for many technologies, industries and countries.A second area of Orsenigo\u2019s research regards the factors affecting the diversity in the patters of innovative activities across industries and the role of the learning environment in affecting these patterns. In several of his work, Orsenigo used the concept of technological regime as one key factor affecting market structure in an industry. Among his various contributions on the issue, one could mention \u201cSchumpeterian patterns of innovation\u201d, , in Regimes reloaded! A reappraisal of Schumpeterian patterns of innovation, 1977\u20132011 revisit this concept and perform a quasi-replication of the original empirical exercise. By using more recent data and an expanded dataset of innovations in several industries and countries compared to the original ones of the 1990s and early 2000, they confirm that that the distinction between Schumpeterian Mark I and Mark II patterns of innovation and their explanation in terms of technological regimes has still a major validity and yields relevant insights concerning on the connection between inventive activities and industrial dynamics.In this special issue, Roberto Fontana, Arianna Martinelli and Alessandro Nuvolari in Industrial and Corporate Change, Vol.5, n.1, 1996; \u201cIndustrial Dynamics: Stylized Facts, Empirical Evidence and Theoretical Interpretations\u201d , Industrial and Corporate Change, 1997, \u201cTechnological Entry, Exit and Survival\u201d , Research Policy, 1999; \u201cThe Persistence of Innovative Activities: A Cross-Country and Cross-Sectors Comparative Analysis\u201d (with E. Cefis), Research Policy, 2001. Industrial dynamics has been identified by Luigi as one of the fundamental aspects of change in the economies and the typical example of Schumpeterian competition. In his empirical work, Luigi has examined the processes that lead to the entry and exit of innovators across a broad range of technologies and the persistence of those firms that continue of innovate over time. Moreover, the analysis has been conducted at the micro level over a long period of time and has used patent data at the firm level across different technologies and different countries. The main findings are that the entry and exit processes are technology specific and that a lot of persistency of innovative activities is usually present. However persistency is not very high in the aggregate and declines as time goes by.A third area of inquiry has concerned industrial dynamics, and particular firms\u2019 persistence in innovative activity and the entry and exit of innovators. Among Luigi\u2019s papers, we would like to highlight \u201cThe Dynamics and Evolution of Industries\u201d , Along these lines, in this Special Issue Elena Cefis, Franco Malerba and Orietta Marsili present a paper initially discussed with Luigi, \u201cRevolving door effect\u201d or \u201cSchumpeterian gale of creative destruction?\u201d. The authors claim that two basic patterns of exit can be identified from the literature: the revolving door and the gale of creative destruction. In the first, the liability of newness is a driver of the exit process, while in the second it is the displacement of non-innovators. The authors test these two patterns of exit on the population of Dutch firms exiting in 2018. They find confirmation that exit is industry specific: in fact, these two patterns characterize different types of industries. In industries in which innovation does not play a major role, the revolving door effect is the typical pattern and exit is concentrated among the adolescent and small firms. On the contrary, in industries in which innovation is relevant, exit takes place both among infant as well as mature firms and does not necessarily involve only the smaller firms. In particular, in a highly innovative environment, the exit of mature firms is driven by the innovation of young firms as a case of gale of creative destruction.The Economic Journal, 1988, a model with firms heterogeneous in their behaviour and with feedback loops driving the diffusion process. The model shows that diffusion is a dynamic process with a dynamic coupling between the behaviour of individual agents and the environment in which they operate.As an evolutionary economist, Luigi has often emphasized the widespread and persistent heterogeneity of firms in innovation and diffusion. On this theme, Luigi published \u201cInnovation, Diversity and Diffusion: A Self-Organisation Model\u201d, (with G. Silverberg and G. Dosi), In this Special Issue, firms\u2019 heterogeneity is at the base of the paper by Stefano Brusoni, Lorenzo Cassi and Simge Tuna \u201cReinventing the tire: knowledge integration between technical change and strategy making\u201d. In the article, heterogeneity is examined in terms of the different strategies that Pirelli and Michelin (two of the tire industry\u2019s major companies), followed to exploit robotized modular manufacturing, a radical process innovation. Of the two firms, Pirelli, the technological follower, was more successful because it had a more nuanced strategy due to its superior knowledge integration capabilities. By examining the structural characteristics and evolution of inventors\u2019 networks in the two companies, the authors are able to take into account knowledge integration capabilities. Pirelli leveraged a more connected, cohesive and structured skills than Michelin and developed and deployed a more complex strategy that could better fit the characteristics of the new process technology.Industrial and Corporate Change, 1999. \u201cInnovation and Market Structure in the Dynamics of the Pharmaceutical Industry and Biotechnology: Towards a History-Friendly Model\u201d , Industrial and Corporate Change, 2002. History friendly models represent a second generation of evolutionary models that focus on the evolution of industries, the dynamics of technologies and industrial change and pay attention to the specificities and histories of industries. In these models a dialogue between empirical analyses of industries, appreciative theorizing derived from these analyses and formal models is developed. The result is that history-friendly models are empirically-grounded, based on a specific empirical evolution of an industry, and aim to capture the causal arguments of the appreciative theory in a stylized and simplified form. The building of the model provides a vehicle for checking out the consistency and relevance completeness of the arguments presented in the appreciative theory. Like most evolutionary models, history-friendly models take the form of computer simulations, and are \u201cagent-based modelling\u201d.One last area in which Luigi has been involved in the last part of his life has been the development of a second generation of evolutionary models: history friendly models. Please see in this respect the book \u201cInnovation and the Evolution of Industries: History Friendly Models\u201d , Cambridge University Press, 2016; and the articles \u201cA History-Friendly Model of the Evolution of the Computer Industry\u201d, , The Journal of Evolutionary Economics, 2007). Another model looks at the presence of a variety of market segments that allow entrants to compete in environmental niches that are rather separate one from another .Some of history-friendly models however do not concern industry evolution but examine specific topics in innovation and industrial dynamics. Among these topics, some models analyse the role of demand. A model examines the role of experimental users able to nurture a new technology that may then improve over time and challenge the dominant technology , the advancements of our understanding of the dynamics of industries in general, and of biotechnology in particular, so much pushed and led by Luigi are not only impressive but agenda setting. Remarkable above all is Luigi\u2019s ability to putting empirical regularities into a dynamic instead of a static approach in a clever way, developing a sense for, and understanding of the endogenous forces of change, and striping the complexity of real world phenomena down to a set of dynamic mechanisms and forces. That requires a sound understanding of economic theory, a good sense of scientific ingenuity, as well as a superb competence to creatively put together pieces of puzzles. Luigi quite obviously demonstrated such abilities in a superb way and his contributions to advancing the theory and empirics of industrial dynamics and evolution have been outstanding and path-breaking.So far, this Introduction has been mainly centred on Luigi\u2019s scientific and scholarly work. In the following pages we expand the scope of the tribute to Luigi, by including the talk given by one of us at the opening of the Conference in honour of Luigi Orsenigo in 2018. The Conference gathered his friends, colleagues and former students, and represented a significant testimony of his work, personality and social life.Innovation and the Evolution of Industries:History Friendly Models\u201d\u00a0, Cambridge University Press, 2016Leveraging Science for Innovation. Swedish Policy for University-Industry Collaboration (with M. Jacob), 1990\u20132005, SNS, Stockholm, 2007The Economics of Biotechnology (with M. Mc Kelvey (eds.)), Edward Elgar, Cheltenham, 2006Tra continuita\u2019 e cambiamento. La storia dell\u2019Agip Petroli (with G. Sapelli and P. Toninelli), Bologna, Il Mulino, 1993The Emergence of Biotechnology. Institutions and Markets in Industrial Innovation, Pinter Publishers, London, 1989Booksb)Eurasian Business Review\u00a0(2019) 9:1\u201323History friendly models: retrospective and future perspectives ,\u00a0Industrial and Corporate Change, 2019Spinoffs in context ,\u00a0Journal of Economic Policy, 2016Industrial Policies for Biotechnology: Limits and New Perspectives, , Business History, Special Issue on \u201cMaking Sense of Today\u2019s Structures, by Re-introducing Evolutionary Theory to Business History\u201d, 2015The Evolution of the Pharmaceutical Industry\u201d Journal of Artificial Societies and Social Simulation, 2013A Simulation Model of the Evolution of the Pharmaceutical Industry , Long Range Planning, 2013Are Switching Costs Always Effective in Creating First Mover Advantage? The Moderating Role of Demand and Technological Regimes , Journal of Economics and Statistics, 2013Innovation and market structure in the evolution of the pharmaceutical industry: a history friendly model, , The Journal of Evolutionary Economics, 2012Technological regimes and demand structure in the evolution of the pharmaceutical industry , Structural Change and Economic Dynamics, 2010User-producer relations, innovation and the evolution of market structures under alternative contractual regimes , Research Policy, 2010In Defence of the Linear Model: An Essay , Capitalism and Society, Berkeley Electronic Press, 2008Technological Revolutions and the Evolution of Industrial Structures. Assessing the Impact of New Technologies upon Size, Patterns of Growth and Boundaries of Firms, , Health Partnerships Review, 2008Beyond market failures: IAVI and the organizational challenges of vaccine development (with S. Brusoni and E. Cacciatori), International Journal of Biotechnology, Special Issue on The Evolution of the Life Science Industries (ed. with J. Tait), 2008Editorial, International Journal of Biotechnology, 2008Special Issue on The Evolution of the Life Science Industries (ed. with J. Tait), Journal of Economic Behaviour and Organisation, 2008Public Policies and Changing Boundaries of Firms in a \u201cHistory Friendly\u201d Model of the Co-Evolution of the Computer and Semiconductors Industries , ), Industrial and Corporate Change, 2008The Italian Connection: the origins of Giovanni Dosi\u2019s thinking and a note on some lost, or never written, manuscripts , European Planning Studies, 2008, pp. 337\u2013357A Critical Assessment of Regional Innovation Policy in Pharmaceutical Biotechnology (with A.Rosiello), Structural Change and Economic Dynamics, 2007Testing Gibrat\u2019s Law: A Bayesian Approach to the Study of Firms\u2019 Growth (with E. Cefis and M. Ciccarelli), The Journal of Evolutionary Economics, 2007Demand, Innovation and the Dynamics of Market Structure: the Role of Experimental Users and Diverse Preferences , European Journal of Development Research, 2007The International AIDS Vaccine Initiative (IAVI) in a Changing Landscape of Vaccine Development: A Public \u2013 Private Partnership as Knowledge Broker and Integrator , Revista de Economia, 2003History Friendly Models of Industrial Evolution: Aims, Applications and Pitfalls, International Journal of Technology Management, 2003Variables Influencing Industrial Funding of Academic Research in Italy: an Empirical Analysis (with G. Bruno), Revue d\u2019Economie Industrielle, 2002The Intensity of Competition After Patent Expiry in Pharmaceuticals. A Cross-Country Analysis (with L. Magazzini and F. Pammolli), Industrial and Corporate Change, 2002Innovation and Market Structure in the Dynamics of the Pharmaceutical Industry and Biotechnology: Towards a History-Friendly Model , Journal of Artificial Societies and Social Simulation, 2001History-Friendly Models: An Overview of the case of the Computer Industry , Research Policy, 2001The Persistence of Innovative Activities: A Cross-Country and Cross-Sectors Comparative Analysis (with E. Cefis), Small Business Economics, 2001The (failed?) development of a biotechnology cluster. The case of Lombardy, Research Policy, 2001Technological Change and the Dynamics of Networks of Collaborative Relations. The Case of the Bio-pharmaceutical Industry (with F. Pammolli and M. Riccaboni), Sistemi Intelligenti, 2000Mente e societ\u00e0: soluzione di problemi e organizzazioni , International Journal of Industrial Organization, 2000Competition and industrial policies in a \u201chistory-friendly\u201d model of the evolution of the computer industry , Industrial and Corporate Change, Special Issue on \u201cThe Codification of Knowledge\u201d (eds: P. Cohendet and W.E. Steinmueller), 2000Knowledge, Innovative Activities and Industry Evolution , The Economic Journal, April, 2000Technological regimes and Schumpeterian patterns of innovation , Industrial and Corporate Change, 1999A History-Friendly Model of the Evolution of the Computer Industry , International Journal of Biotechnology, 1999The evolution of the forms of organization of innovative activities in biotechnology (with P. Barbanti e A. Gambardella), in Research Policy, 1999Technological Entry, Exit and Suvival , Journal of Management and Governance, 1998The Dynamics of Knowledge and the Evolution of an Industry Network , The International Journal of Industrial Organization, 1997Technological Persistence and Heterogeneity of Innovative Activities, Sectoral Patterns of Innovation and International Specialization , Industrial and Corporate Change, Special Issue on Technological Regimes and the Evolution of Industrial Structures, edited by G. Dosi, F. Malerba and L. Orsenigo, 1997Technological Regimes and Sectoral Patterns of Innovative Activities , Industrial and Corporate Change, Special Issue on Technological Regimes and the Evolution of Industrial Structures\u201d, edited by G. Dosi, F. Malerba and L. Orsenigo, 1997Industrial Dynamics: Stylized Facts, Empirical Evidence and Theoretical Interpretations , , Industrial and Corporate Change, edited by G. Dosi, F. Malerba and L. Orsenigo, 1997Special Issue on Technological Regimes, Industrial Demography and the Evolution of Industrial StructuresCahiers de Economie et Sociologie Rurale, 1996Technological regimes, patterns of innovative activities and industrial dynamics. A survey of empirical evidence and of some theoretical models, Industrial and Corporate Change, Vol.5, n.1, 1996The Dynamics and Evolution of Industries , Research Policy, 1996Schumpeterian patterns of innovation are technology-specific , The Journal of Evolutionary Economics, 1995Choice and action , Small Business Economics, 1995Technological Regimes, Selection and Market Structures , Cambridge Journal of Economics, 1995Schumpeterian patterns of innovation , Biotechnology Review, Special Issue of The International Journal of Technology Management, 1993Scientific gatekeepers and industrial development in biotechnology (with N. Buratti and A. Gambardella), Industrial and Corporate Change, 1993Technological Regimes and Firm Behaviour\u201d, , Ekonomiaz, 1992Regularidades en las actividades de innovacion: una investigacion preliminar para cuatro paises europeos, CSC Ricerche, n. 112, Roma, 1995Competenze tecnologiche nei settori ad alta tecnologia, , Centro Studi Confindustria, Business and Economic History, 1992The evolution of strategy and structure of a state-owned company: the case of Agip Petroli (1960-1990) (with G. Sapelli and P. Toninelli), L\u2019impresa, no. 4, 1989Concorrenza e collaborazione tra imprese nel processo innovativo: il caso della biotecnologia, The Economic Journal, Vol. 98, December 1988Innovation, Diversity and Diffusion: A Self-Organisation Model (with G. Silverberg and G. Dosi), Rivista Trimestrale di Scienze dell\u2019 Amministrazione, n.2, 1988Tecnologie emergenti e politica industriale in Italia (with P.Adams), Politica ed Economia\u201d, Agosto 1987Modelli di diffusione dell\u2019innovazione, Papersiii)Technological Regimes and Demand Structure in the Evolution of the Pharmaceutical Industry , in\u201c: Andreas Pyka, Esben Sloth Andersen (eds.) Long Term Economic Development, Demand, Finance, Organization, Policy and Innovation in a Schumpeterian Perspective, Springer, 2013Intellectual Property Rights: Legal and Economic Challenges for Development,\u00a0Initiative for Policy Dialogue, Oxford, Oxford University Press, 2014IPRs, Public Health and the Pharmaceutical Industry. Issues in the Post-2005 TRIPS agenda\u201d (with B. Coriat), in M. Cimoli, G. Dosi, K.E. Maskus, R. L. Okediji and J. H. Reichman,\u00a0The Palgrave Encyclopedia for Strategic Management, Macmillan, London, 2013Pharmaceuticals, in M. Augier and D. Teece (eds.), Capitalism and Society 3.1 (2008)Technological Revolutions and the Evolution of Industrial Structures. Assessing the Impact of New Technologies upon Size, Patterns of Growth and Boundaries of Firms\u201d, ,\u00a0The Development Agenda: Global Intellectual Property and Developing Countries\u201d, Oxford University Press, 2008IPRs, technological and industrial development and growth: the case of the pharmaceutical industry (with F. Laforgia and F. Montobbio), in N. Netanel (ed.), \u201cBusiness Performance in the twentieth Century: A Comparative Perspective, Cambridge University Press, Cambridge, UK, 2008Innovate or Die? A critical review of the literature on innovation and performance (with S. Brusoni and E. Cefis), in Y. Cassis and A. Colli (eds), The Elgar Companion to Neo-Schumpeterian Economics, Elgar, Cheltenham, 2007\u201cHistory Friendly\u201d Models of Industrial Evolution, in H. Hanusch and A. Pyka (eds.), Promoting innovation, productivity and industrial growth and reducing poverty: bridging the policy gap London: Routledge,. (2008)The International AIDS Vaccine Initiative (IAVI) in a changing landscape of vaccine development: a Public Private Partnership as knowledge broker and integrator in Chataway, J.C., Mackintosh, M. and Wuyts, M. (eds.) The Genesis of Clusters of Innovation, Oxford, Oxford University Press, 2006Clusters and Clustering in Biotechnology: Stylised Facts, Issues and Theories. From Clusters to network structures and their dynamics, in P. Braunerhjelm and M. Feldman (eds.), New Frontiers in the Economics of Innovation and New Technology. Essays in Honour of Paul A. David, Edward Elgar, Cheltenham, 2006A history-friendly model of innovation, market structure and regulation in the age of random screening in the pharmaceutical industry , in C. Antonelli, D. Foray, B. H. Hall and W.E. Steinmueller (eds.), Knowledge Accumulation and Industry Evolution. The Case of Pharma-Biotech\u201d\u201d, Oxford University Press, Cambridge, Cambridge University Press, 2006The Dynamics of Knowledge Accumulation, Regulation and Appropriability in the Pharma-Biotech Sector: Policy Issues (with G. Dosi and M. Mazzucato), in G. Dosi and M. Mazzuccato (eds.), Knowledge Accumulation and Industry Evolution. The Case of Pharma-Biotech\u201d, Oxford University Press, Cambridge, Cambridge University Press, 2006Entry, Market Structure and Innovation in a History-Friendly Model of the Evolution of the Pharmaceutical Industry , in G. Dosi and M. Mazzuccato (eds.), Revue del\u2019OFCE, 2006Biotechnologies et industrie pharmaceutique. Un mod\u00e9le \u00e9volutionaire conforme \u00e0 l\u2019histoire\u00a0, Knowledge Accumulation and Industry Evolution. The Case of Pharma-Biotech, Cambridge, Cambridge University Press, 2006Heterogeneity in Firms\u2019Growth in the Pharmaceutical Industry (with E. Cefis and M. Ciccarelli), in G. Dosi and M. Mazzuccato (eds.), Flexibility and Stability in the Evolving Economy, Oxford University Press, 2005Changing Boundaries of firms in the evolution of the computer industry: towards a history-friendly model , in M. McKelvey and M. Holmen (eds.), Saggi di economia evolutiva, Franco Angeli, Milano, 2005Prefazione, in F.M. Lombardi and F. Squazzoni (eds.), Imprese e Storia, 31, gennaio-giugno 2005Modelli \u201chistory-friendly\u201d della evoluzione industriale, \u201cMultidisciplinary Economics\u201d, Springer, Dordrecht, The Netherlands, 2005History Friendly Models of Industrial Evolution: An Overview, in P. De Gijsel and H. Schenk, The Economic Dynamics of Modern Biotechnology, Edward Elgar, London, 2005Reflections and Ways Forward (with H. Kettler e M. McKelvey), in M. McKelvey, A. Rickne and J.L. Hellman, Sectoral Systems of Innovation, Cambridge University Press, Cambridge, 2004Pharmaceuticals Analyzed through the Lens of a Sectoral Innovation System (with M. McKelvey and F. Pammolli), in F. Malerba (ed.), Informacion Comercial Espanola\u201d, 2004Los \u201cmodelos amistosos de la istoria\u201d en el analisis de la evolucion de las industria: objetivos y aplicaciones, Handbook of Economic Sociology, Cambridge (Mass.), Russell Sage, 2004Technology and the Economy (with G. Dosi and M. Sylos Labini), in N. Smelser and R. Swedberg, The SMS Blackwell Handbook of Organizational Capabilities. Emergence, Development and Change, Blackwell, Oxford, 2003Firm Capabilities, Competition and Industrial Policies in a History-Friendly Model of the Computer Industry , in C. Helfat (ed.), The Economics of Choice, Change and Organization. Essays in honour of R. Cyert, Edward Elgar London 2001\u201cA behavioral and evolutionary model of the dynamics of the computer industry\u201d , in M. Augier and J. March (eds.),\u00a0Economia e Politica Industriale, 2001Modelli History friendly della evoluzione delle industrie: il caso dell\u2019industria dei computer , \u201cSimulating organizational societies.\u201d, Cambridge (Ma.), MIT Press, 2001Product Diversification in a \u201cHistory-Friendly Model of the Evolution of the Computer Industry , in E. Larsen and A. Lomi (eds.), The Competitive Renaissance of the US Industry, Washington DC, The National Academy, 2000The Determinants of Research Productivity in Pharmaceuticals and Biotechnology: Implications for Public Policies , paper prepared for the STEP Board Conference on Technological and Non-technological Factors in Industry Performance, Washington D.C., 19,997; D. Mowery (ed.), The Sources of Industrial Leadership, edited by D. Mowery and R. 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Freeman (eds.), \u201cInnovazione tecnologica e servizi alle imprese\u201d, edited by C. Filippini, F. Angeli, Milano, 1992L\u2019accumulazione delle capacita\u2019 tecnologiche nell\u2019industria italiana (19869-84) , in Conferenza nazionale sul commercio estero. L\u2019internazionalizzazione dell\u2019impresa, Atti, Vol. II, Roma, 1992La competitivita\u2019 tecnologica internazionale dell\u2019industria italiana negli anni ottanta , in Ministero del Commercio Estero e Istituto Nazionale per il Commercio estero, Technology and Productivity. The Challenge for Economic Policy, OECD, Paris, 1991Microeconomic dynamics and macro regularities: an \u201cevolutionary\u201c approach to technological and institutional change (with F. Coricelli e G. Dosi), in State Policy and Techno- Industrial Innovation, London, Routledge, 1991State Policies on Techno-Industrial Innovation in Weaker Economies. The Case of Biotechnology in Britain and Italy (with W. Faulkner), in U. Hilpert (ed.) Struttura, risultati e problemi dell\u2019industria chimica in Italia, Milano, SC Sviluppo Chimica, 1991L\u2019 evoluzione dell\u2019industria chimica italiana negli anni \u201880 (with G. Mussati e A. Soru); La piccola e media industria chimica in Italia: i risultati dell\u2019indagine\u201d (with A. Soru); \u201cLe grandi multinazionali chimiche in Italia (with A. Soru), in CeRIC-Federchimica,\u00a0Innovazione tecnologica e teoria economica, edited by M. Amendola, Bologna, Il Mulino, 1990Teoria evolutiva e innovazione industriale: gli anni \u201880 , in Alle origini dell\u2019imprenditorialita\u2019, a cura di G. Mussati, Milano, Etas Kompass, 1990Processi di formazione di nuove imprese e dinamica industriale: uno schema di riferimento concettuale (with Marco Vivarelli), in Evolving Technology and Market Structure, Ann Arbor, Michigan University Press, 1990Technological Regimes and Patterns of Innovation: A Theoretical and Empirical Investigation of the Italian Case , in M. Perlman and A. Heertje (eds.), Il settore dei servizi nella societa\u2019 e nell\u2019economia italiana. Matrice 1970-1988., edited by R. Fiori and F. Stellatelli, Milano, CESDIT, 1989Crescita del terziario per l\u2019industria, processi di esternalizzazione e innovazione, in Tecnologia: collaborare e\u2019 d\u2019obbligo, edited by G. Mussati, Confindustria, Comitato Nazionale Piccola Industria, Sipi, Roma, 1989Processi innovativi nelle piccole e medie imprese, in Industria italiana e alte tecnologie\u201d\u00a0edited by F. Onida and R. Malaman, Milano, F. Angeli, 1989I pattern di sviluppo della biotecnologia: il quadro di riferimento internazionale nei primi anni \u201880, in \u201cTechnical Change and Economic Theory.\u201d, Frances Pinter, London,1988Coordination and Transformation: An Overview of Structures, Behaviour and Change in Evolutionary Environments (with G.Dosi),in G. Dosi, C. Freeman, R. Nelson, L. Soete and G. Silverberg (eds.), \u201cTechnology, Innovation and Finance\u201d, Oxford, Basil Blackwell, 1988; translations in Italian, French, German and SpanishIndustrial Structure and Technical Change\u00a0(with G. Dosi),\u00a0in A. Heertje (ed.),\u00a0Evoluzione della struttura finanziaria, ruolo degli Istituti di credito a medio e lungo termine e tendenze del credito agevolato, edited by\u00a0P. Ranci, Assireme, Milano 1983La riforma del credito agevolato (with P. Ranci e G. Verga) in\u00a0Evoluzione della struttura finanziaria, ruolo degli Istituti di credito a medio e lungo termine e tendenze del credito agevolato, edited by P. Ranci, Assireme, Milano 1983Il finanziamento delle piccole e medie imprese, in\u00a0La programmazione dei flussi finanziari, edited by G. Vaciago, Il Mulino, Bologna, 1983Il finanziamento delle imprese nella programmazione dei flussi finanziari, in Chapters in books"} +{"text": "In the published article, there was an error regarding the affiliations for Ayyad Zartasht Khan. As well as having affiliations \u201cDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, Norway, Department of Surgery, S\u00f8rlandet Hospital Arendal, Arendal, Norway, Department of Ophthalmology, S\u00f8rlandet Hospital Arendal, Arendal, Norway,\u201d he should also have the following affiliation: \u201cInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Joachim Robert Kalden, Born 23, 1937 in Marburg; \u2020passed away February 6, 2021 in Erlangen.The VIII European Workshop for Rheumatology research held in Corfu, Greece, in the spring of 1988, gave the opportunity to a handful of experts on Autoimmune Rheumatic disorders (ARDs), from different European counties, to constitute a group with a main goal to transform EULAR from a physical medicine and orthopaedics society to a contemporary League, supporting research towards understanding the pathogenesis and development of novel therapies for ARDs. This group consisted of Professors Ravinder Maini, JR Kalden, LBA van de Putte, Allan Wiik, I Lundberg, Lars Klareskog, J Smolen, P Youinou, and myself. I invited these experts for further discussions towards the materialisation of our goal, in a follow up meeting. For everyone\u2019s convenience, this meeting was held close to the Athens airport, in the Astir palace hotel in Vouliagmeni, Attiki, Greece. Among these experts, a leading role was held by the now late Joachim Robert Kalden, a Lupus expert and subsequently a member of the leading group that introduced anti-TNF therapy for rheumatoid arthritis. Professor Kalden developed in Erlangen a world-renowned and respected centre for diagnosis, understanding the pathogenesis of lupus and application of novel therapeutic interventions in ARDs. In addition to research, Johan has edited, in collaboration with other colleagues, three books: (1) Progress in Immunology: Vol. VII: Proceedings of the 7th International Congress of Immunology Berlin 1989; (2) Rheumatoid Arthritis: Recent Research Advances in 1992; and (3) Der IL-1-Rezeptor-Antagonist im Zytokin-Netzwerk: Funktion und Stellenwert in 2013. Furthermore, he shared his knowledge and accomplishments with pleasure, everywhere he was invited to speak.These memoirs came to my mind when I heard from Prof J Smolen that our beloved colleague and one of the founders of research centres in Europe for the study of ARDs, lost the war after a prolonged fight with SARS-COV2.We will remember him as a well-organized personality, a thoughtful investigator, a didactic teacher, and sincere mentor for the development of younger colleagues as clinicians, therapists, and researchers.We, his friends and colleagues, lost a great friend, an advisor in difficulties, and a joyful companion to have a glass of wine with good food. The Aegean Sea and islands will miss a lover of their unique bright light, blue sky and waters. Johan, we will always remember you."} +{"text": "Author Contributions appears below.Julian Maier was not included as an author in the published article. The corrected \u201cMI, ML, GL, MB, HS, and DL designed the study. MI, JM, MH, KJ, and DL conducted the experiments. MI, MB, HS, and DL analyzed data. MI and DL wrote the manuscript with significant input from all other authors.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Artificial intelligence (AI) is a new technical discipline that uses computer technology to research and develop the theory, method, technique, and application system for the simulation, extension, and expansion of human intelligence. With the assistance of new AI technology, the traditional medical environment has changed a lot. For example, a patient\u2019s diagnosis based on radiological, pathological, endoscopic, ultrasonographic, and biochemical examinations has been effectively promoted with a higher accuracy and a lower human workload. The medical treatments during the perioperative period, including the preoperative preparation, surgical period, and postoperative recovery period, have been significantly enhanced with better surgical effects. In addition, AI technology has also played a crucial role in medical drug production, medical management, and medical education, taking them into a new direction. The purpose of this review is to introduce the application of AI in medicine and to provide an outlook of future trends."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cCollege of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China,\u201d it should be \u201cShenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.\u201dIn the published article, there was an error regarding the affiliation for Chen Chen. As well as having affiliation 1, they should also have \u201cCollege of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, China.\u201dThere was another error regarding the affiliation for Guo-Li Song. As well as having affiliation 1, they should have \u201cShenzhen Bay Laboratory, Shenzhen, China\u201d and \u201cShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Cajanus cajan (L.) Huth] plays an important role in preserving poor smallholders' major source of income in the tropics and subtropics by improving food and feed security, particularly protein intake. In the meantime, protein deficiency is frequent in tropical and subtropical regions due to rapidly increasing human populations and the high cost of animal-origin proteins. As a result, pulse crops should be their primary source of protein. Among these, PP is the most important pulse crop utilized as a food component in rain-fed agricultural conditions with the lowest costs, and it is the best source of protein supplements in typical cereal-based diets to fill the nutritional deficit. Despite this, it is the world's least-used pulse crop. Therefore, the primary goal of this review was to provide and synthesize scientifically confirmed and up-to-date information on the dietary usage of pigeon pea for food and feed. Protein, carbohydrates, minerals, vitamins, and essential amino acids are all present in reasonable amounts in both mature and immature PP seeds. PP has the most potential for usage as food and feed, and its nutrients are comparable to those of soybeans and maize. PP's green leaves, roots, seeds, and pods are high in phenolic compounds, which have anti-inflammation, antibacterial, antioxidant, anticarcinogenic, and antidiabetic properties, as well as the ability to cure diseases like measles, smallpox, chicken pox, sickle cell anemia, fever, dysentery, hepatitis, and antimalarial medications for the body. Furthermore, the addition of pigeon pea and its by-products improves ruminant and nonruminant animal feeding performance significantly. In general, PP products such as dried grain, fresh , and green pods are used as a low-cost (low-cost) source of high-quality and quantity of protein food and feed for tropical and subtropical populations' livelihoods.Pigeon pea (PP) [ Cajanus cajan (L.) Huth] is the most prevalent fast-growing and adaptable pulse crop [2, with India accounting for 92% of that [In tropical and subtropical climates, pigeon pea (PP) [lse crop . Cajan plse crop . The tot of that . It is a of that , 5. It h of that . PP prov of that . PP is a of that . PP is w of that , and it of that .PP seeds contain about 20\u201322 percent protein and appreciable amounts of essential amino acids and minerals . It is tIn addition to its food and feed value, PP's green leaves, roots, seeds, and pods contain a large number of phenolic compounds, which offer a number of health benefits , 24. FurThis narrative review is based on theories and empirical findings, with saturated information extracted. Experiments and scientific findings were utilized to filter data and focus on recent publications. The period of search for this script is from June 01, 2021, to October 30, 2021. The script's literature search focused primarily on the dietary use of pigeon pea for food and feed. The information provided by Google Scholar, as well as peer-reviewed major indexers such as Web of Science, PubMed, and Scopus, was used to extract useful information during this review script. Thus, key words such as \u201cpigeon pea cultivation,\u201d \u201cnutritive profile of pigeon pea,\u201d \u201crole of pigeon pea as food,\u201d \u201crole of pigeon pea as feed,\u201d and \u201ctherapeutic uses of pigeon pea\u201d were used to find journal articles, papers, books, and symposia. The next section of this script will go through some concepts and experimental settings from the perspectives of PP production, pigeon pea nutritional profile, and dietary usage of pigeon pea for food and feed, and pigeon pea medicinal uses.PP was first grown in India, but it is the world's least utilized pulse crop. It does, however, provide certain benefits for smallholders in the tropics and subtropics . India, The early-blowing variants of PP, as shown in For a village production system, three to four PP seeds might be placed on a single hill, and the plants would generate a large number of twigs on both sides of the bund. In other words, a field with a track record of strong soil fertility and drainage should be selected for periurban commercial cultivation. For soil shortages, a 100\u2009kg/ha diammonium phosphate application and other soil adjustments are recommended prior to sowing. Plant PP seed, as shown in PP is a good source of carbs, proteins, fats, and minerals, and it makes a significant contribution to human and animal nutrition. Carbohydrates, proteins, minerals, vital amino acids, and vitamins are abundant in both mature (dry) and immature seeds of PP . PP seedThe main carbohydrates contained in PP are soluble sugars, starch, and dietary fiber. According to a study by , the comProteins are the second most important component of PP, with 21.7\u2009g/100\u2009g of protein in ripe (dry) seeds, as shown in In mature and immature PP seeds , palmitiAccording to Dietary inhibitors such as phytolectins, polyphenols, and enzyme inhibitors are found in small levels in the mature seed of PP . AccordiPP is consumed in a variety of ways as a food . MeanwhiPP's leaves, seeds, and roots are used for a variety of therapeutic purposes . For exaPigeon pea seed extract has also been found in clinical investigations to aid in the reduction of red blood cell sickling, suggesting that it may be beneficial for people with sickle cell anemia. Sickle cell anemia can be treated with pigeon peas. Many sickle cell disease patients in Chhattisgarh utilize pigeon pea to decrease erythrocyte sickling . The PP According to multiple studies, the leaves, seeds, and roots of PP have a significant degree of anti-inflammation and antibacterial characteristics , 80, as Several studies have found that PP and its by-products are excellent fodder (forage) species that are necessary for animal feed . The PP On the other hand, sheep selected fresh PP plants (forage) from eight browse forge species , and theIn chicken and pig feeds, the whole seed, pods, pod husks, hay, and milling by-products of PP could be a superior replacement for soybeans and maize . SimilarAccording to Whiteman and Norton , adding According to Singh and Kush , PP planThe purpose of this narrative review was to discover the nutritional and phenolic components of pigeon pea, as well as their relevance in human and animal nutrition. In the meantime, protein deficiency is frequent in tropical and subtropical regions, owing to a rapidly growing human population and the high cost of animal-origin proteins. As a result, pulse crops should be their primary source of protein. PP is the most important pulse crop utilized as a food component under rain-fed agricultural circumstances, and it is the most important source of protein supplements in traditional cereal-based diets to fill the nutritional deficit. Protein, carbs, minerals, vitamins, and fundamental amino acids are all present at reasonable levels in both mature and immature PP seeds. PP has the most potential for usage as a food and feed source, and its nutrients are comparable to those of soybeans and maize. In addition to its dietary value, PP's green leaves, roots, seeds, and pods contain a large number of phenolic compounds, which have anti-inflammatory, antibacterial, antioxidant, anticarcinogenic, and antidiabetic properties, as well as the ability to treat diseases such as measles, smallpox, chicken pox, sickle cell anemia, fever, dysentery, hepatitis, and antimalarial medications. Furthermore, the addition of PP and its by-products improves the performance of ruminant and nonruminant animal nutrition significantly. In addition to the foregoing explanations, PP contains antinutritional substances that may have an adverse effect on nutrient bioavailability. Chemical soaking and cooking techniques, on the other hand, may help mitigate these antinutritional effects. Smallholder farmers in the tropics and subtropics use PP and its by-products, such as dry grain, green pods and pod husks, and hay, as a low-cost source of edible proteins for food and feed. As a result, significant emphasis should be put on the production and utilization of PP in traditional cereal-based diets in order to fight protein deficiency in developing countries."} +{"text": "Colorectal cancer (CRC) represents one of the most frequent human cancer entities and is still amongst the \u201ctop killers\u201d in human cancer, although fundamental progress has been made in recent years in CRC prevention, early diagnosis, basic and translational research, and (targeted) therapy. The current Special Issue, \u201cColorectal cancers: from present problems to future solutions\u201d, presents 13 highly timely articles, 9 original articles and 4 reviews, which give insights into, and highlight, the latest developments within the scientific, translational and clinical CRC community, presenting views and work of several internationally highly recognized experts in the field. To this end, the special issue covers exciting novel discoveries in basic and mechanistic research that help to understand CRC carcinogenesis, progression and metastasis, tumor cell heterogeneity, and novel microenvironmental components in CRC. It also covers clinical parameters that modify CRC characteristics and therapy response, and tools and models with a high innovative potential to open new chapters in the differential diagnosis of CRC heterogeneity and response to therapy. causes of CRC carcinogenesis, progression, metastasis, and/or CRC interaction with the (micro-) environment. In an exciting review, Nobel Laureate Harald zur Hausen and Ethel-Michele de Villiers give an intriguing overview on a potential, completely novel class of infectious agents, which might open new avenues to our understanding of indirect carcinogenesis, but also further chronic diseases, such as type 2 diabetes, as (co-) caused by bovine meat and milk factors (BMMFs) [Several articles present advances or novel, in part provocative, hypotheses on (BMMFs) . BMMFs r (BMMFs) systemat (BMMFs) in CRC. (BMMFs) extends (BMMFs) .tumor cell heterogeneity is certainly still one of the most unresolved problems we are facing when it comes to cancer individual diagnosis, prediction, risk classification, and therapy. Ideally, we would like to aim at scenarios and early diagnostic tools that enable us to predict, for every single patient, the likelihood to develop later progressive disease or metastasis, before this actually happens macroscopically. Therefore, methods to identify metastatically \u201cdangerous\u201d tumor cell clones in any primary tumor, or within single disseminated tumor cells that can be identified in, e.g., the blood of cancer patients, would open tremendous opportunities for a more individualized risk prediction and (preventive) therapy stratification. In an interdisciplinary consortium of molecular translational oncology researchers, optical physicists, and chemists, the groups of H.A. Wagenknecht, C. Cremer, and our own group recently succeeded in establishing a first-in-field approach for quantitative single-cell, single molecule localization microscopy (SMLM) at the nanoscale, within resected human CRC tissues [The issue of tissues . We spec tissues present tissues . These cclinical characteristics (age and gender), can have an impact on clinical courses and outcomes in CRC, and, potentially, response to therapy. During recent years, it has been observed that sporadic CRC has been increasing, also, in younger patients. In an attempt to address potential causes for this, in a large multinational cohort of over 2100 newly diagnosed CRC patients, Himbert et al., together with many colleagues involved in the ColoCare study, analyzed patient, demographic, and lifestyle characteristics, compared between age of onset younger than, or over, 50 years [Two further articles of this Special Issue show actual clinical study data, illustrating how, up to now rather neglected 50 years . Althougmodelling colorectal cancer. A highly interesting article by Jens Hoffmann and his group [Translational, and re-translational, research in CRC, and its success and impact for clinical consequences will, ultimately, also depend on the availability of the right models that are able to reflect the situation within a CRC patient as authentically as possible. Therefore, two articles in this special issue introduce novel, and timely, means of is group introducis group introducTaken together, with this Special Issue, \u201cColorectal Cancers: From Present Problems to Future Solutions\u201d, we hope to present an exciting compilation of articles, by well-known international experts, which can deepen discussions and ideas amongst colleagues in all kinds of disciplines working at CRC and beyond. I hope it can encourage, and intensify, even more translational and interdisciplinary collaborations, aiming at an ultimate understanding of strategies to defeat, and prevent, colorectal cancer, its progression and metastasis, and all the suffering and death resulting from it."} +{"text": "Following the publication of this article , the firPLOS ONE Editors retract the article.In light of the data ownership issues, the CJW, YQL, LLL, YRG, and RHB agreed with the retraction. LW, LYZ, and MXZ either did not respond directly or could not be reached."} +{"text": "Nature Communications 10.1038/s41467-021-25027-2, published online 06 August 2021.Correction to: The original version of this Article contained an error in the author list affiliations, which was previously given as Charles Langmuir is from \u2018State Key Laboratory of Isotope Geochemistry, Guangzhou Institute of Geochemistry, Chines Academy of Sciences, Guangzhou, China\u2019 and the \u2018Department of Earth and Planetary Sciences, Harvard University, Cambridge, MA, USA\u2019. The correct version states that Charles Langmuir is from the \u2018Department of Earth and Planetary Sciences, Harvard University, Cambridge, MA, USA\u2019. This has been corrected in both the PDF and HTML versions of the Article."} +{"text": "NOT by single effect/mechanism/pathway), these Neurotransmitters and Neuropeptides by themselves can activate, rejuvenate, and improve T cells. \u201cPersonalized Adaptive Neuro-Immunotherapy\u201d is a novel method for rejuvenating and improving T cells safely and potently by Neurotransmitters and Neuropeptides, consisting of personalized diagnostic and therapeutic protocols. The patient\u2019s scarce and/or dysfunctional T cells are activated ex vivo once by pre-selected Neurotransmitters and/or Neuropeptides, tested, and re-inoculated to the patient\u2019s body. Neuro-Immunotherapy can be actionable and repeated whenever needed, and allows other treatments. This adoptive Neuro-Immunotherapy calls for testing its safety and efficacy in clinical trials.T cells are essential for eradicating microorganisms and cancer and for tissue repair, have a pro-cognitive role in the brain, and limit Central Nervous System (CNS) inflammation and damage upon injury and infection. However, in aging, chronic infections, acute SARS-CoV-2 infection, cancer, chronic stress, depression and major injury/trauma, T cells are often scarce, exhausted, senescent, impaired/biased and dysfunctional. People with impaired/dysfunctional T cells are at high risk of infections, cancer, other diseases, and eventually mortality, and become multi-level burden on other people, organizations and societies. It is suggested that \u201cNerve-Driven Immunity\u201d and \u201cPersonalized Adoptive Neuro-Immunotherapy\u201d may overcome this problem. Natural Neurotransmitters and Neuropeptides: Glutamate, Dopamine, GnRH-II, CGRP, Neuropeptide Y, Somatostatin and others, bind their well-characterized receptors expressed on the cell surface of na\u00efve/resting T cells and induce multiple direct, beneficial, and therapeutically relevant effects. These Neurotransmitters and Neuropeptides can induce/increase: gene expression, cytokine secretion, integrin-mediated adhesion, chemotactic migration, extravasation, proliferation, and killing of cancer. Moreover, we recently found that some of these Neurotransmitters and Neuropeptides also induce rapid and profound decrease of PD-1 in human T cells. By inducing these beneficial effects in na\u00efve/resting T cells at different times after binding their receptors ( T cells are essential for eradicating infectious organisms and cancer, immune response to injury, organ repair, and for various other health-promoting missions . T cells-left side), the T cells of numerous people in various abnormal conditions (-right) are scarce and/or exhausted, senescent, impaired, biased, and often also suffer from altered stemness and therefore do not function properly.However, in contrast to T cells of healthy subjects are characterized by low proliferation in response to antigen stimulation, progressive loss of effector function (cytokine production and killing function), expression of multiple inhibitory receptors such as PD-1, Tim3, and LAG3, and metabolic alterations from oxidative phosphorylation to glycolysis , 9\u201316. ET cell senescence or biological aging is a process that results from a variety of stresses, and leads to a state of gradual deterioration of functional characteristics and irreversible growth arrest , 16\u201318.T cell stemness is characterized by the capacity of T cells to self-renew, and be multipotent. T cell stemness combines the ability of a T cell to perpetuate its lineage and give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration , 19.-right and in further detail in its legend, due to word limit of this paper).Individuals who have scarce and/or exhausted, senescent, altered and dysfunctional T cells are very susceptible and at high risk of morbidity and mortality, and become a harsh multi-level clinical, physiological, and economic burden on many other people, organizations, and societies , hepatitis B virus (HBV), hepatitis C virus (HCV), and other microorganisms, and in cancer , 9\u201316.+ T cells are important for protective immunity against intracellular microorganisms and tumors, but in chronic infections or cancer, the CD8+ T cells are exposed to persistent antigen and/or inflammatory signals, leading to a gradual deterioration of their function, a state called \u201cexhaustion\u201d. Tex are characterized by progressive loss of effector functions (cytokine production and killing function), expression of multiple inhibitory receptors (such as PD-1 and LAG3), dysregulated metabolism, poor memory recall, homeostatic self-renewal, homeostatic proliferation, and distinct transcriptional and epigenetic programs , and these cells suffer from anergy, exhaustion, senescence, and impaired stemness , 14, 15.Thus, the T cells of cancer patients are often dysfunctional and unable to eradicate the cancer cells efficiently, due to many different reasons. On top of the above-mentioned division into general categories, the reasons and factors that limit and/or impair the T cells of cancer patients can be divided into distinct families, each containing multiple specific members, as discussed in detail in . Among tFactor family 1: Lack of antigen processing, T cell recognition and TCR signaling; Factors family 2: Negative immune modulation; Factors family 3: Non-accessibility of tumor to T cells; Factors family 4: Immune editing, equilibrium and escape . Due to On these grounds, an effective and safe rejuvenation of scarce, exhausted and dysfunctional T cells, and induction of multiple beneficial T cell functions in cancer patients, remain an urgent desired clinical goal.+CD25+ and CD4+FoxP3+ regulatory T cells (Tregs), synergistic decreased function of effector T cells (Teffs) and antigen presenting cells (APCs), and a shift of the Th1 to Th2 cytokine responses have impaired adaptive immunity characterized by a greater vulnerability to viral infections and deficient responses to vaccinations, along with decreased number and/or activity of T cells and natural killer cells (NKCs) .low/CCR4+ Tregs, and memory Tregs, and reduced CD56+CD16- (putative immunoregulatory) NKC counts (+ T cells of MDD patients are characterized by higher frequencies of CD4(+)CD25(high)CD127(low/-) cells, higher FOXP3 mRNA expression, and less diverse TCR V\u03b2 repertoires ,5. Be patient-friendly and painless, do not necessitate hospitalization or any other procedure or treatment, and allow continuation of everyday life during therapy,6. Be applicable to many people in very different ages and abnormal conditions, who suffer from scarce, sub-optimal and dysfunctional T cells,7. Allow repeated and timely therapy whenever needed, and for as long as needed, and as such allow even prolonged periodic treatment over months and years, for people with chronic T cell dysfunction,8. Be flexible and contain several build in options and modalities, allowing higher degree of freedom and action,9. Contain preliminary personalized ex vivo diagnostic cellular functional tests that can be done at any time, using small quantity of the patient's own T cells , and reliable biomarkers. These ex vivo tests should be able to evaluate the present condition of the patient's T cells, and measure their ex vivo responsiveness to the planned adoptive cellular therapy. As such, these diagnostic tests could evaluate and predict the person\u2019s potential benefit from tentative treatment and to tailor personalized regimen,a priori the antigen/s expressed on the disease-causing cells or microorganisms. Therefore, the method should not be limited to, or suitable only for, cases in which either the tumor antigens or the antigens of infectious organisms (e.g. the spike protein of Covid-19) are known and can be used.10. Be independent of a prerequisite of knowing 11. Not depend on, and not utilize, the T cell receptor (TCR) and its associated proteins, for avoiding both further Activation-Induced Cell Death (ACID), T cell exhaustion, and the risk of autoimmunity,12. Not manipulate the T cells genetically,in vitro for prolonged periods, for not losing some essential traits/capabilities. It is especially important that the therapeutic method would not impair T cell ability to migrate and home to, and penetrate into, various organs and tissues which either contain disease-causing cells or infectious organism, or are injured and require T cell help for healing,13. Not park/culture the T cells in vivo activity is dependent on cytokines or growth factors and need such subsequent support in vivo. Thus, the therapeutic method should preferably be free of any detrimental side effects of systematically-administered cytokines (e.g. IL-2), and of any cytokine storms,14. Not use T cells whose 15. Not perform any pre conditioning procedure prior to the therapy itself , and do inject any drug before, during, or after the infusion of the adoptive transfer of the patient's rejuvenated and improved T cells,ex vivo process of T cell rejuvenation, activation and amplification, prior to the inoculation of the patient's improved T cells into his body,16. Not change, inactivate or even suppress transiently any natural receptors, ion channels, or other proteins expressed on the T cell surface during the in vivo cytokine storms and competition over natural ingredients and space. Settle with much less T cells injected repeatedly over few weeks or months17. Not necessitate single infusions of billions of improved T cells each time, for avoiding 18. For conditions which are NOT cancer, use and adoptively transfer rejuvenated and improved T cells which can be \u201cfriendly\u201d to, and communicate with, other cells, rather than very aggressive T cells which may damage, or compete with other cells for natural resources and space, in lymphoid organs, and in other tissues and organs, and which may also cause autoimmunity,19. The new immunothreapy should stand on its own, as a mono therapy, for saving, prolonging, and improving life, but must not interrupt or compete with any other efficient treatment/drugs from which the person can benefit from, and which may overcome T cell exhaustion and allow better T cell function. Thus, any other prior, simultaneous, in between, or later safe and effective treatment would be possible, as long as they do not harm T cells and do not induce immunosuppression.20. On top of being used on their own, it would be advantageous if the diagnostic and therapeutic methods and protocols of the new immunotherapy could be used also as \"add on technologies'', and allow improvement of other adoptively-transferred therapeutic T cells.T cell immunotherapies , 35 haveIn line with this scientific and clinical revolution, there is an enormous number of scientists and clinicians working on T cell immunotherapies, and a meteoric rise of companies developing and utilizing them, primarily for cancer, but also for some infectious diseases. Current adoptive/cellular T cell therapies include mainly the following types: donor lymphocyte infusions, tumor-infiltrating lymphocytes, T-cell receptor-engineered T cells, chimeric antigen receptor (CAR) T cells, and virus-specific T cells. These T cell immunotherapies are reviewed in many papers, among them , 35.While each of these potent T cell immunotherapies has their own clear focus, advantages, and successes, primarily for some types of cancer, to the best of my knowledge none can rejuvenate and rescue T cells from exhaustion and senescence whenever needed and for whoever needs it, and that manage to improve multiple T cell functions simultaneously, among them increase migration, homing and extravasation into tissues .I\u2019m also not aware of adoptive T cell immunotherapies that fulfil all, or at least most, of the 20 suggested criteria specified in the preceding section, and are suitable for broad use for all, at least most conditions of scarce, exhausted, suboptimal, and dysfunctional T cells.How can we safely and potently rejuvenate, activate, and improve scarce, exhausted and/or senescent T cells whenever needed and fulfil the 20 suggested criteria for optimal solution defined in the previous section?ex vivo natural Neurotransmitters and Neuropeptides , many of which are specified below in the next chapters, in the cited papers, and in language , 37, 46,\u201359, manyi.e. \u201ctalks\u201d directly to T cells in various parts of the body via Neurotransmitters and Neuropeptides, that in turn bind to their specific receptors in T cells (as well as many others cells) and induce on their own multiple direct, rapid, potent, timely and beneficial effects. I further hypothesize that T cells need Neurotransmitters, Neuropeptides and their receptors, and the direct, rapid and potent effects they induce, for performing multiple health-guarding T cell tasks, and for communicating with the brain and with other body systems and organs.My idea and suggestion are to try to mimic and translate into therapeutic terms, what I hypothesize that the nervous system most probably normally does in everyday life: Neurotransmitters are traditionally defined as endogenous chemical substances used by the nervous system to transmit messages, either between neurons, or from neurons to muscles, or from neurons to gland cells. In addition, many Neurotransmitters induce direct effects on T cells and other immune cells, as well as on different cell types which express their receptors.i.e. peptides, produced and released by neurons through the regulated secretory route, and acting on neural substrates. Once again, T cells and other immune cells ought to be added as target cells that are affected directly by Neuropeptides.Neuropeptides are traditionally defined as small protein-like molecules, via its own functional Neurotransmitter/Neuropeptide receptors that are highly expressed in these cells , induce multiple direct and potent beneficial effects on resting/na\u00efve T cells CD3+ T cells of healthy subjects purified from their blood, which are in normal number and condition (+ T cells of few patients with Head and Neck cancer - Head and Neck Squamous Cell Carcinoma (HNSCC) and of f (HNSCC) .de novo gene expression , evident at various time points after their binding to their receptors in T cells, the above-mentioned Neurotransmitters and Neuropeptides can on their own improve dramatically many essential T cell functions.Together, by inducing all these direct and beneficial effects that bind to the T cell\u2019s PD-1 and by doing so keep T cells in an inactive/suppressed mode, and prevent T cell reactivity against themselves. Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells. These drugs have shown a great deal of promise and success in treating certain cancers.****+ peripheral T cells of few elderly people aged 79\u201386 years, suffering from HCC and a kaleidoscope of comorbid conditions. We also tested the effects of these Neurotransmitters and Neuropeptides on CD3+ na\u00efve/resting T cells of additional healthy subjects. In all cases, the CD3+ T cells were purified from small blood samples.In our most recent study (submitted paper) we studied the direct effects of Dopamine, Glutamate, GnRH-II, CGRP or Neuropeptide Y induced the following effects: A. Decreased significantly both the percentage of PD-1+ T cells and the level of PD-1 expression per cell , B. Increased, up to seven fold, the number of alive T cells that proliferated in vitro in response to human HCC cells (either HepG2 or Huh7 cell line), C. Increased significantly killing of human HCC cells in vitro by the T cells (up to 2 fold increase).We found all the following significant findings: 1. The HCC patients had 5\u201310 fold less T cells than healthy subjects, 2. The patient\u2019s T cells were abnormal, Moreover, we found that few unexpected combinations of Neurotransmitters and Neuropeptides induced even stronger effects than the single Neurotransmitters/Neuropeptides, and that Dopamine D1-5R agonists, of which D4R was the best, also decreased PD-1 and increased T cell numbers.via their own receptors in T cells, and by inducing multiple beneficial effects. Yet, once again, we found significant inter-individual variability with regard to the effects of these Neurotransmitters and Neuropeptides on human T cells.Together, these findings demonstrate that Dopamine, Glutamate, GnRH-II, Neuropeptide Y and CGRP, each on its own or in combinations, can activate, rejuvenate, and improve T cells, even when they are scarce and suboptimal T cells of elderly people with cancer and several diseases, and that they do so in low physiological concentration, single exposure and direct manner\u2014Personalized Adoptive Neuro-Immunotherapy\u201d, drawn schematically in Based on the all the experimental findings in hand so far and the corresponding publications , 36\u201345, I propose that the \u201cPersonalized Adoptive Neuro-Immunotherapy\u201d has the ability to rejuvenate, activate and improve T cell number, condition, migration and function. By doing so, this novel type of adoptive cellular therapy may hopefully increase survival, improve life quality, and prevent multiple harsh multi-level implications , proliferative response to cancer, killing of cancer, ability to recruit other immune cells to the site of disease or injury, and most probably additional advantageous effects not revealed yet.T adhesion to extracellular matrix glycoproteins, chemotactic migration, homing, extravasation into solid organs, gene expression, cytokine secretion, expression of key proteins , is essential and beneficial for all involved sides, and can be translated into therapeutic terms , according to the needs of the entire body either in health or disease;2. Direct, accurate, real-time, and beneficial T cell activation, which is dictated by the brain and other parts of the nervous system, in a coordinated and orchestrated manner, and which takes place whenever needed, and wherever needed (via natural Neurotransmitters and Neuropeptides and their respective receptors expressed in T cells, which can take place independent of the TCR and specific foreign antigens. Thus, the activation of T cells via Neurotransmitters and Neuropeptides is not antigen-specific, and as such it can be safer, broader, and maybe even better in few contexts, since it is not expected cause neither TCR-mediated autoimmunity against self antigens, nor TCR-mediated T cell exhaustion upon repeated exposure to tumor antigens or infectious antigens.3. Rapid, transient and advantageous T cell activation Whole body control, orchestration, coordination and adaptation, allowable by the direct real-time information conveyed to, and received from, T cells and other immune cells, in either health or disease.I humbly propose that we may have the ability to protect, improve, and even save many people\u2019s lives, by using and actually mimicking the natural \u201clanguage\u201d by which the brain \u201ctalks\u201d to T cells, for new and potentially very safe and effective mode of therapy\u2014The \u201cPersonalized Adoptive Neuro-Immunotherapy\u201d (If the \u201cPersonalized Adoptive Neuro-Immunotherapy\u201d turns out to be indeed safe, effective and patient-friendly, an enormous number of people whose T cells are malfunctioning, as well as their relatives, health caregivers, healthy services, hospitals, insurance companies, and entire societies, could benefit from it (Moreover, I foresee that repeated periodic strengthening of T cells of people at risk, especially in older age, can become almost routine, generic, and broad spectrum method of immune-protection, not limited each year only to few selected microbial organisms. The current Covid-19 pandemics teach all of us a devastating and warning lesson: relying only on vaccinations to already identified viruses and other infectious organisms, is not sufficient, and can lead to disastrous worldwide implications.The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Callyspongia encompasses a group of demosponges including 261 described species, of which approximately 180 have been accepted after taxonomic reviews. The marine organisms of Callyspongia are distributed in tropical ecosystems, especially in the central and western Pacific, but also in the regions of the Indian, the West Atlantic, and the East Pacific Oceans. The reason for the interest in the genus Callyspongia is related to its potential production of bioactive compounds. In this review, we group the chemical information about the metabolites isolated from the genus Callyspongia, as well as studies of the biological activity of these compounds. Through NMR data, 212 metabolites were identified from genus Callyspongia , belonging to classes such as polyacetylenes, terpenoids, steroids, alkaloids, polyketides, simple phenols, phenylpropanoids, nucleosides, cyclic peptides, and cyclic depsipeptides. A total of 109 molecules have been reported with bioactive activity, mainly cytotoxic and antimicrobial action. Thus, we conclude that polyacetylenes, terpenoids and steroids correspond to the largest classes of compounds of the genus, and that future research involving the anticancer action of the species\u2019 bioactive metabolites may become relevant.The genus Callyspongia Duchassaing and Michelotti, 1864, belonging to the family Callyspongiidae and the order Haplosclerida, is structured in six subgenera: Callyspongia Duchassaing and Michelotti, Callyspongia Carter, Callyspongia Schmidt, Callyspongia (Euplacella) Lendenfeld, Callyspongia Ridley, and Callyspongia (Spinosella) Vosmaer indole-3-carboxylic acid (116a) indole-3-carboxylic acid (116b) acetic acid (209); acetic acid (210); and the callypyrones A (211) and B (212). Except for substances 211 and 212 that were isolated from an EtOAc/MeOH 1:1 of Callyspongia diffusa . Ot. Ot5) annd 32\u201338 . In addictively, .Callyspongia sp. and have driving Th1 polarization and antiproliferative effect against HL-60 and HCT-15 . \u03b2-. \u03b2-60) alminthic , antimutlminthic , angiogecompound was founlminthic , antifunium spp. , antidiacompound was founium spp. , analgesium spp. ,106, antium spp. , anti-inium spp. ,113,114,ium spp. ,113,114,ium spp. , and immium spp. .105) was evaluated as a potential compound for anti-HIV action, by inhibiting type 1 of this virus with an infection vector to 1/3 at 200 nM in a 96-well plate .169 ; c; c196) ictively) ,145. Bas0 5.3 \u03bcM . Bastadiof IMPDH , while bXF 22RV1 . Other cctively) . Lastly,Callyspongia is composed of various species of sponges, in which 261 have been described and approximately 180 accepted by reviews of taxonomists [Callyspongia sp. species were also considered in the bibliographic survey, but their non-identification makes the distinction between them impossible, allowing only a speculative approach based on localities of origin of these sponges. However, these results suggest that there are still many Callyspongia sponges that can be studied.The genus onomists ,4. AlthoCallyspongia was published in 1981 [Callyspongia species. Still, during this period, two species of Shiphonochalina have been taxonomically reclassified and are currently known as Callyspongia lindgreni [Callyspongia siphonella [The first study about the isolation of metabolites from in 1981 and the in 1981 ,63. Analruncata) ,33 and Cphonela) ,61,62,63Callyspongia, in which 103 are categorized in two classes, polyacetylenes (1\u201347), and terpenoids and steroids (48\u2013104), in agreement with previous studies that present substances of this class as characteristic in the genus. In this sense, because of the greater number of isolations in different species, polyacetylenes could be classified as chemical markers for Callyspongia [In total, 212 metabolites were identified from yspongia ,27.54\u201388) were also extensively documented, being the first isolated metabolites according to the investigations of this review [Callyspongia siphonella. In addition, most of isolated compounds were collected from sponges of Red Sea regions, China, Japan, Indonesia, and Australia. This fact highlights the potential for further research in regions where the genus is less explored, such as Brazil, Ecuador, and Barbados, for example. It is also important to note that in some studies, no trace was found on the place of origin of the marine material studied [The sipholane triterpenoids , and the isolation of compounds from beings that establish symbiotic relationships with Callyspongia species [Molecules abolites ,42 and tabolites , F [4,22abolites . The unarization , identifrization , Mass Sprization ,147 have been reported as bioactive . In this sense, the results are in agreement with the data that prove the relevance of the metabolites in the genus with anticancer action [Some of the 212 metabolites reported herein were described in original reviews and articles as biologically relevant. Among these compounds, 109 molecules . The species were classified by nomenclature and researched individually. Additional information was obtained by searching for the term \u201cCallyspongia\u201d accompanied by keywords specific to the articles, such as the species name, the collection site, the name of the isolated metabolites and the types of biological activity. In addition, the data of biological activities of metabolites were searches by the name of the structures accompanied by the terms \u201cbiological\u201d, \u201cactivity\u201d and \u201cbiological activity\u201d.The selection of articles proceeded using inclusion criteria, i.e., the characterization of molecules by NMR as the primary criterion and the presence of biological activity as the secondary. The articles were identified by means of a summarized reading of the published content. The investigations reached a total of 973 articles, of which, 145 were considered compatible with the inclusion criteria, and selected for the review.Through NMR data, 212 metabolites were identified from genus Callyspongia , which were classifying into the following groups: polyacetylenes, polyketides, terpenoids and steroids, simple phenols and phenylpropanoids, alkaloids, nucleosides, cyclic peptides and cyclic depsipeptides, and miscellaneous .Callyspongia genus are producers of several classes of primary and secondary metabolites, mainly polyacetylenes and lipids. In addition, many of these compounds are biologically active and have activities that may prove to be promising in fighting diseases. Thus, this literature review gathered essential information for the emergence of new research on the species of the genus.Sponges of the"} +{"text": "The authors wish to make the following corrections to the paper : During 1Thi Tuong Vy Phan 1\u00a0phanttuongvy4@duytan.edu.vnCenter for Advanced Chemistry, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Hai Chau, Danang 550000, Vietnam; We apologize for this unintentional mistake, which, however, does not affect the results of this manuscript and the conclusions drawn from them."} +{"text": "During original publication of Jaeschke, K., Hanna, F., Ali, S., Chowdhary, N., Dua, T., & Charlson, F. . the disDisclaimer:The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated."} +{"text": "The original version of this article unfortunately contained a mistake. The following affiliation of all three authors had not been included and was added retrospectively: Shriners Hospitals for Children, Northern California, Orthopedics, Sacramento, CA, USA.The original article has been corrected."} +{"text": "In \u201cPrecision Public Health Campaign: Delivering Persuasive Messages to Relevant Segments Through Targeted Advertisements on Social Media\u201d :e22313) the authors noted one error.In the originally published manuscript, the order of authors Ingmar Weber and Hanya M Qureshi was reversed. This has been corrected to reflect that Hanya M Qureshi is the paper\u2019s third author and Ingmar Weber is the paper\u2019s fourth author. The author affiliations have been renumbered accordingly.The full list of authorship and affiliations in the originally published version appeared as follows:1, PhD; Haewoon Kwak1, PhD; Ingmar Weber2, PhD; Hanya M Qureshi3, BAJisun An1School of Computing and Information Systems, Singapore Management University, Singapore, Singapore2Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar3Yale School of Medicine, Yale University, New Haven, CT, United StatesThe full list of authorship and affiliations has been updated as follows in the corrected version:1, PhD; Haewoon Kwak1, PhD; Hanya M Qureshi2, BA; Ingmar Weber3, PhDJisun An1School of Computing and Information Systems, Singapore Management University, Singapore, Singapore2Yale School of Medicine, Yale University, New Haven, CT, United States3Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, QatarThe correction will appear in the online version of the paper on the JMIR Publications website on October 5, 2021, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories."} +{"text": "Saudi Arabia, a prominent Arabian country, has 35. 3 million persons living in 2.2 million square kilometers, undergone serious threats recently due to the COVID-19 pandemic. With the built-in infrastructure and disciplined lifestyle, the country could address this pandemic.This analysis of COVID-19 cases in Saudi Arabia attempts to assess the situation, explore its global percentage share, percentage of population affected, and local distribution from the beginning of infection until recently, tracing historical developments and changes.This analysis made use of data released by the Ministry of Health on a daily basis for a number of parameters. They are compiled on an excel sheet on a daily basis: the dataset has undergone rigorous analysis along with the trends and patterns; proportion to the world statistics and geographic distribution.COVID-19 spread rapidly in the country with periodic variations, during June-August, 2020. But, recoveries accelerated in the period, thus bridging the gap of increasing infections. In comparison with the world statistics, the country proportions are lower, while the percentage of population affected is similar. It appears that the intensity varied across all 13 administrative areas.COVID-19 transmission since March 2020 is considered to be widespread, creating excess burden on the public health system, delineated into stages . Control measures are set, stage-wise, without impinging upon normal life but to ensure that the proportion of globally affected persons is lesser than the population share: credit goes to the Ministry of Health. Area-wise spread depends largely on population density and development infrastructure dimensions. Ultimately, the disciplined life in compliance with law and order paved the way for effective program implementation and epidemic control. The COVID-19 pandemic spread rapidly across the world, including Saudi Arabia, which led to a severe health emergency . There aThe epidemic period combined with health emergencies created tensions in family units, especially under poor conditions of infrastructure and crowded living arrangements due to restrictions on family and social life, interpersonal contact, and affective gestures adhering to the strict discipline of social distancing and face masks . This leSaudi Arabia, a large country in terms of geographic area, is divided into five planning regions, 13 administrative areas, and 118 governorates. It borders five Arabian Gulf countries and a few other Arab countries, and accommodates a combined native and foreign population of 35.3 million across 2.2 million square kilometers. This predominantly urban country built residential, commercial, educational, medical, and other infrastructure to encourage community living, which expedites the possibility of faster infection , 21. FloAgainst this backdrop, this research aims at an epidemiological analysis of COVID-19 cases reported on a daily basis to highlight changes, patterns, and trends over a period from March 21, 2020 to November 22, 2021. With the limitations of the national-level data available for analysis, this research elucidates the path of COVID-19 infection in the country, from its very beginning until recently. Such an elaboration, which has not yet been attempted, might enlighten researchers, policymakers, and practitioners to track historically and to learn lessons from a successfully implemented infection control program. Not only does this elaboration exposes the Saudi Arabian experience to global readers, but also it gives data and insights to the rest of the world, especially the Arab countries.This empirical study adopting ex-post facto approach is based solely on daily status reports of the Ministry of Health of Saudi Arabia published since March 21, 2020. Calculations were done to determine:a. daily changes in infectionb. daily differences between reported and recovered casesc. daily changes in active cases and critical casesd. case fatality rate e. new and active cases, recovery and mortality as a percentage of globalf. infections, recoveries, and deaths per 100,000 populationwww.worldometers.info) as a denominator, indicators such as (a) daily reported cases, (b) total cases and total recoveries, (c) total deaths, (d) critical cases, (e) active cases, and (f) vaccinations are calculated for a base population of 100,000.Data published contained city-wide data till November 28 2020; thereafter it was by the 13 administrative areas till September 25, 2021; and at national level totals there. There were reports of global figures too till September 25, 2021. It was owing to the substantial decline in infection that these changes in the data structure are enacted by the Ministry of Health. Furthermore, adopting population size on daily reports of COVID-19 cases published on the Website and through social media platforms (Facebook) by the Ministry of Health, Saudi Arabia. These reports from March 21, 2020 to November 22, 2021 are compiled on an Excel worksheet for consolidated analyses and illustrations.Results of this analysis are presented under various headings: epidemiology, proportion to world statistics, percent of the population affected, and spread by administrative area.A total of 392 cases of COVID-19 recorded on March 21, 2020, increased to 549,518 on November 22, 2021 showing a rapid spread in a population of 35.3 million; unexpected and un-afforded to the public health system. Fortunately, there were reductions in reported infection per day from 4,757 on June 18, 2020 to 220 on November 28, 2020; 328 on February 28, 2021; 1,161 on June 7, 2021 and 39 on November 22, 2021 . Along wTwo of the important indicators are active cases and critical cases: the former, as reported, increased from 22,444 on June 3, 2020, to 63,026 on July 13, 2020, but declined sharply thereafter. While the increase from June 3 to June 19 was sharp, it slowed down thereafter, reaching 45,157 on July 22, 2020; 23,687 on August 23, 2020; and 8,487 on October 19, 2020; 1,894 on January 16, 2021; and 2,296 on September 25, 2021. On November 28, 2020, there were 5,018 active cases , which declined to 2,584 by February 28, 2021; 2,581 on March 4, 2021 but thereafter increased to 9,376 on June 7, 2021. While the rapid increase in active cases noted during March 21-June 12, 2020 could be considered as part of the first phase, those noted in 2021 could be explained as part of the second phase. The total number of infections and recoveries has been varied but bridged the gap since October 2020. Moreover, the gap widened and shortened depending upon the daily reports. On the contrary, dwindling changes in the critical cases were recorded on a daily basis until the end of January, and started to climb up thereafter. For example, on June 3, 2020 there were 1,321 critical cases that increased to a peak of 2,295 on July 4, 2020, decreased to 352 on January 30, 2021 and thereafter increased to 1,579 on June 7, 2021. The same started falling slowly, thereafter, reaching a figure of 52 on November 22, 2021.Increases in the daily number of infected cases were in multiples of hundred during the early days of COVID-19. For example, on March 24, 2020, the number of new cases was increased by 154. But on July 3, 2020 the highest daily increase was reported as 810, which reduced from August onwards. On the contrary, there were reductions too, for example, on April 8, 2020, there was a reduction of 135 cases. Along with the spread of infections, mitigation also took place resulting in recoveries from the episodes. As of February 28, 2021, 368,305 cases have been recovered out of a total number of infections of 377,383 cases reported, representing a 97.6% recovery rate, leaving 6,494 (1.7%) deaths, which shows a prevalence of 0.7%. During the early days, that is, March and April 2020, daily recoveries were lower than reported cases, which is the reason for a huge increase showing negative recovery-reported case statistics. For example, on March 24, 2020, this difference was 196, with 9 recoveries out of 205 cases. On May 4, 2020, this figure of recovery-reported cases reached \u22121,303 and on June 12, 2020 it reached a peak of 2,911 cases, adding up to active cases. On the other hand, there were recoveries exceeding new cases from May 12, 2020 onwards but were zigzagging: the highest on July 14, 2020 with a difference of 5,026 cases .The case fatality rate, calculated as total deaths to 1,000 total infected cases, reached 16.3 on June 7, 2021. It was recorded as 15.1 on April 6, 2020, which declined to 5.4 by May 23, 2020. However, case fatality was recorded at a high of 17.3 during January 6\u2013February 16, 2021, and 8,826 on 22 November, 2021 depending mostly on the positive cases and deaths reported. The total number of deaths reached 7,471 on June 7, 2021 with a daily mortality of 16. The highest number of deaths of 58 was reported on July 5, 2020.Saudi Arabia, the largest country in the Arabian Gulf and second largest in the Arab World, has an area and population that are both 0.4% of the world. Saudi Arabia started with 0.2% of the world's COVID-19 cases on March 21, 2020, which increased to 1.5% by June 20, 2020, but declined to 0.02% by November 28, 2020, 0.01% by February 28, 2021, and even less than that thereafter, following various phases of intervention over that period . RecoverThere are a total of 549,518 infected cases, as of November 22, 2021 ; higher rates of infection but almost all recovered . Thus, having a very narrow gap between infected and recovered persons . It is tSome of the administrative areas, especially major commercial, educational, residential, and developmental zones, reportedly have a higher number of COVID-19 cases . In RiyaCOVID-19, the most critical health issue humans have ever experienced over the last decade, vary across countries in intensity raising global issues by creating severe health and socioeconomic concerns, thus precipitating global disruption and emergencies affecting other aspects of life, including travel, material, and financial resources, and psychosocial wellbeing , 33\u201335. Chronologically, risk assessment was followed by suspension of religious, recreational, sports, and commercial gatherings and thereafter public transport regulations leading to a partial curfew. There were enforced restrictions of inter-regional and international and national movements, local curfews based on daily reports, and national level lockdown. Connections are maintained through e-services. Repatriation of citizens, isolation of districts, remote teaching procedures, and rules carrying reprimands for the violation of control measures were also introduced. The private sector and expatriates were offered financial and welfare support along with special terms during Ramadan. Control measures were lifted slowly, step by step, depending upon the locational volume of spread. Mass testing strategies were initiated and, thereafter, normal living was regained in Saudi Arabia. There were a few other control measures put in place during the second wave too, although the spread was less intense. Slowly, there were reductions in the spread and thereby control measures were removed in the Kingdom. By this time, immunization programs gained momentum and it became mandatory for movement, especially in public places and offices. As an outcome, by September 2021, almost all control measures were withdrawn, observing a noticeably low spread of COVID-19. There exist restrictions on international travel and the entry of non-immunized people into the country. This is based on the lessons gained about the onset of the disease carried to the country by frequent travelers of the Eastern Region.Mortality, measured as case fatality, was observed to be high, which increased rapidly until January 2021: such higher mortality rates might have resulted from population age distribution, the age of infected persons, life expectancy, comorbidity, treatment-seeking behavior, and other risk factors . HoweverCOVID-19 spread to more than 200 locations in Saudi Arabia, and thus gripped the country for a period, which was addressed through medical and legal intervention. This reduced not only the gap between infection and recovery but also the proportion to global infection, recovery, and mortality. While the global figures continue to increase rapidly, the share of Saudi Arabia declined, which may be credited to the mitigation efforts.Population size and density are potential sources of COVID-19 infection , especiaThere were increases in the overall total cases and mortality, which are attributed to the waves of this epidemic on a global basis. But, threats are limited as revealed by the affected persons as a percentage of the population. Thus, population rates are more meaningful than the absolute numbers for understanding the impact of COVID-19 on societies. These rates show the extent COVID-19 impacts the population regarding distribution, economy, behavior, and cohesiveness, directly and indirectly. These achievements of continued decline are geared by strenuous efforts of healthcare intervention including daily detection tests and vaccination.Saudi Arabia has gone through highs and lows; based on population size, urban growth, infrastructure in place, and economic sectors. For example, a high spread of disease reported in administrative areas such as Riyadh, Makkah Al-Mokarramah, and the Eastern Region corresponds to this view. The second set of administrative areas are Al-Madinah Al-Monawarrah, Aseer, Al-Qassim, and Jazan. The other areas had few infected cases. These variations across administrative areas could directly relate to urbanization, social and religious festivities, commercial activities, and livelihoods despite effectively implementing various containment measures all over the country , 23, 39.COVID-19 in Saudi Arabia witnessed increases and decreases epidemiologically, in terms of new cases, mortality, active cases, and critical cases, delineating phases of early infections , heightened spread , fast decline , stabilization , second-wave , and full control (October 2021 onwards). While country statistics show remarkable control, credit goes to the committed efforts of the Ministry of Health, Saudi Arabia, and disciplined adaptations by the public. Overall, the percentage of population affected is low, comparatively, but should be kept in view for continued efforts to control the virus. Mitigation along with infection control strategies should go hand in hand in a strengthened manner.Geographically, administrative areas with higher pressures of population migration and socioeconomic development are more affected, especially the major cities such as Riyadh, Jeddah, Makkah, Buraydah, Dammam, and Madina. Finally, it is the disciplined life in compliance with a law and order situation under a government of utmost accountability that enabled the achievement of goals and targets in time.This research has many limitations, especially those related to data. Still, with this available data on the national scenario, the overall situation is explained for the global audience. It would have been more insightful had there been detailed data on age and sex specificity of infections, recoveries, and mortality. Such details could also be beneficial for analysis across geographic locations.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.AS: initiation, concept development, data compilation, analysis, and writing. RA-K: advisory in data compilation and methodology, reviewing and revising, and enabling supportive mechanisms. IE: assisting in data compilation, helping in analysis and literature review, and reviewing and suggesting improvements. All authors contributed to the article and approved the submitted version.Deanship of Scientific Research at King Saud University, Riyadh, for its funding of this research through the Research Group No. RGP-329.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In the published article, there was an error in affiliation 1, instead of \u201cDepartment of Obstetrics, Qingdao Jinhua Hospital, Qingdao, China\u201d, it should be \u201cDepartment of Obstetrics, Qingdao Jinhua Gynecology Hospital, Qingdao, China\u201d.In the published article, there was an error in the affiliation order. The affiliation order should be1 Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China,2 Department of Obstetrics, Qingdao Jinhua Gynecology Hospital, Qingdao, ChinaIncorrect Author OrderIn the published article, there was an error in the order of authors. The author order should be1#*, Lijuan Qi2#, Jinhua Fu2, Shuqin Bi2, Lin Li1 and Yinghui Fu2Long Zhao#Long Zhao and Lijuan Qi contributed equally to this work.The corrected Author Contributions Statement appears below.LZ, LQ, and JF: conception and design, data analysis, and interpretation. LZ: administrative support. LQ, SB, YF, and LL: provision of study materials or patients, collection and assembly of data. All authors: manuscript writing and final approval of the manuscript.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Molecular medicine is emerged with the progression of life science, representing the third medicine revolution after clinical anatomy and experimental medicine in the last centuries. As a multidisciplinary field, molecular medicine integrates physics, chemistry, biology, and medical technology, which aims at deciphering the structural, molecular, and cellular mechanisms that drive pathogenic process and at developing molecular tools and interventions for the diagnosis, prevention, and treatment of human diseases. A milestone in molecular medicine is the launch of Human Genome Project (HGT) in 1990, promoting the advance of diverse subdisciplines including epigenetics, genomics, transcriptomics, proteomics, and metabolomics. As a result, many new pathogenic factors are uncovered in recent years, such as gene mutations in inherited disease, posttranslational modification in aging, and noncoding RNAs in cancer. Assisting by translational medicine, the cutting\u2010edge academic theories and technologies of molecular medicine have been developed into products that improve human health, such as nivolumab for the treatment of nonsmall cell lung cancer, Adalimumab for the treatment of rheumatoid arthritis, and artificial intelligence\u2010driven platform for drug discovery.MedComm to meet the current and future demand, providing a home for this field.With the progress of technologies and the continuous efforts of researchers, there is an advance in our understanding of molecular and translational medicine. However, many challenges are still to be faced. For example, the regulatory network consisting of proteins and nucleic acids is far from understood. Existing targeted therapies for diseases are unable to meet clinical needs. Precise diagnostic technologies, especially for early disease diagnosis, are also inadequate. Growing publications have suggested that this field is a rapidly expanding realm of research. Based on a PubMed Advanced Search (All Fields: \u201cmolecular medicine\u201d), the total number of papers published in 1985 was 47 and increased to 12\u00a0260 in 2002, and further reached to 60\u00a0452 in 2018. However, high\u2010impact journals in this field are limited, as a result, the published articles are vastly decentralized. Furthermore, governments and foundations around the world are increasingly providing financial support to the research in molecular medicine, including molecular diagnosis, molecular pathology, signal transduction, targeted intervention, drug discovery and delivery, and other clinical techniques for managing human diseases. It is expected that more and more important discoveries will be achieved in the near future. However, the limited capacity of existing journals cannot ensure the timely publication of relevant works with an increasing rate. Thus, we are launching MedComm is a peer\u2010reviewed, online open access journal that publishes the pioneer works of medicine on the basis of novelty, timeliness, and significance on human health. Notably, MedComm is a multidisciplinary journal, covering disciplines including but not limited to clinical medicine, molecular biology, cell biology, pharmacology, medicinal chemistry, and pharmacy. Areas of interest contain basic researches that advance the understanding of pathogenesis, such as clinical epigenetics, genomics, proteomics, metabolomics, noncoding RNA, microenvironment, and cellular signal transduction. Researches that improve the diagnosis and treatment of human diseases, such as early disease diagnosis, liquid biopsy, high\u2010definition imaging, gene therapy, cell therapy, immunotherapy, chemical genomics, drug discovery, artificial intelligence in medicine, regenerative medicine, medical nanotechnology, drug delivery, and gene editing, are also interested by MedComm. All the major human diseases, including cardiovascular diseases, cancer, neurodegenerative disease, autoimmune disorders, and other pathologies, are within the scope of MedComm. It has a wide range of authors and readership, including researchers engaged in basic and applied research related to molecular medicine and translational medicine, clinicians concerned with pathogenic mechanism, as well as students in medicine, life science, and drug discovery.MedComm will aperiodically provide news, views, and highlights to comment on the latest medical progress, which timely address controversial topics in medicine.We aim to establish a leading forum for medical research. Research articles section, letters section, and reviews section are open for authors to submit their pioneer works, viewpoints, and summaries in the frontiers of medicine. We will also invite experts to publish cutting\u2010edge reviews in this field. In addition, MedComm is composed of high\u2010impact scientists from all over the world, and welcomes researchers to submit valuable works to MedComm. We promise fast review followed by fair and prompt decisions. Once a manuscript is accepted, our editorial staffs will provide high\u2010quality support to ensure your article is the best that it can be.The editorial team of MedComm provides a platform for students, scientists, and clinicians interested in clinical, basic, and translational medicine to share their discoveries and viewpoints in this field. We are committed to operating the MedComm innovative and timely, aiming to offer valuable and helpful information to you and the community.With advances in high\u2010throughput sequencing and high\u2010resolution analysis technologies, novel pathogenic mechanisms, biomarkers, and targets are continuously revealed, followed by the emergence of new techniques for the diagnosis, prevention, and treatment of human disease."} +{"text": "Twitter data exhibits several dimensions worth exploring: a network dimension in the form of links between the users, textual content of the tweets posted, and a temporal dimension as the time-stamped sequence of tweets and their retweets. In the paper, we combine analyses along all three dimensions: temporal evolution of retweet networks and communities, contents in terms of hate speech, and discussion topics. We apply the methods to a comprehensive set of all Slovenian tweets collected in the years 2018\u20132020. We find that politics and ideology are the prevailing topics despite the emergence of the Covid-19 pandemic. These two topics also attract the highest proportion of unacceptable tweets. Through time, the membership of retweet communities changes, but their topic distribution remains remarkably stable. Some retweet communities are strongly linked by external retweet influence and form super-communities. The super-community membership closely corresponds to the topic distribution: communities from the same super-community are very similar by the topic distribution, and communities from different super-communities are quite different in terms of discussion topics. However, we also find that even communities from the same super-community differ considerably in the proportion of unacceptable tweets they post. Social media, and Twitter in particular, are widely used to study various social phenomena, see for example . We then outline individual research methods applied. Network analysis is used to construct retweet networks, detect communities, and study their evolution through time (subsection Evolving retweet communities). Machine learning is applied to train and evaluate a hate speech classification model (subsection Hate speech classification). Methods of content analysis are used to detect topics discussed in the tweets (subsection Topic detection). In the next section, Results and discussion, we combine the results of individual methods to reveal some interesting insights gained from the collected Twitter data.For this study, we collected a set of almost 13 million Slovenian tweets in the 3\u00a0year period, from January 1, 2018 until December 28, 2020. The set represents an exhaustive collection of Twitter activities in Slovenia. The tweets were collected via the public Twitter API, using the TweetCaT tool and 4,597,865 retweets .A retweet network is a directed graph. The nodes are Twitter users and the edges are retweet links between the users. An edge is directed from the user We form a sequence of network snapshots, with a sliding window of 1\u00a0week, to study the evolution of a retweet network. The snapshots are overlapping, where each snapshot comprises an observation window of 24\u00a0weeks (about 6\u00a0months). We employ an exponential edge weight decay, with half-time of 4\u00a0weeks, to eliminate the effects of the trailing end of a moving network snapshot. This provides a relatively high temporal resolution between subsequent networks, but we later select just the most relevant intermediate timepoints.The set of network snapshots thus consists of 133 overlapping observation windows, with temporal delay of 1\u00a0week. The snapshots start with a network at Informally, a network community is a subset of nodes more densely linked between themselves than with the nodes outside the community. A standard community detection method is the Louvain algorithm ,Build a new network where a pair of the original nodes is linked if their total Co-membership across all the Louvain trials is above a given threshold (90% by default),Identify the disjoints sets which then represent the detected communities.As a result of using Ensemble Louvain, nodes without a clear community membership are isolated and excluded from further analyses. The resulting communities are of approximately the same size as produced by individual Louvain trials, but with drastically improved stability and reproducibility . The only non-political community is Sports. All the remaining, smaller communities, are represented as Rest.Hate speech classification is approached as a supervised machine learning problem. Supervised machine learning requires a large set of examples labeled for hate speech, and typically involves a considerable initial effort to produce such labeled examples. The labeled examples are then used to train classification models to distinguish between the examples of hate and normal speech ,Offensive\u2014tweets include offensive generalization, contempt, dehumanization, or indirect offensive remarks,Violent\u2014the author threatens, indulges, desires or calls for physical violence against a target; this also includes tweets calling for, denying or glorifying war crimes and crimes against humanity.During the annotation process, and for training the models, all four classes were considered. However, in this paper we take a more abstract view and distinguish just between the normal, acceptable speech, and the unacceptable speech, i.e., inappropriate, offensive or violent.The hate speech annotation schema is adapted from OLID , between the annotators and the models, and then compare if a model comes close to the inter-annotator agreement.Several machine learning algorithms were used to train hate speech classification models. First, three traditional algorithms were applied: Na\u00efve Bayes, Logistic regression, and Support Vector Machine with a linear kernel. Second, deep neural networks, based on the Transformer language models, were applied. We used two multi-lingual language models, based on the BERT architecture . In subsection Evolution of offensive topics we focus on the three prevailing topics, and show the evolution of acceptable and unacceptable tweets posted by the top communities.The topic detection method we apply requires to set the number of topics in advance. We experimented with different preset values to find an appropriate level of detail where no obvious topics are neither merged nor split across multiple topics. This experiment resulted in six topics, each defined by a probability distribution over constituent words. In general, a tweet discusses several topics with different probabilities. For easier interpretation of the results, we selected just the most probable topic assigned to each tweet.local Ljubljana, year, price, municipality, road, city, Slovenia, car, water, vehicle, center, Maribor, Euro, apartment, shop, house, registration, firefighter, mayor;sports match, year, Slovenia, show, win, season, movie, team, book, city, Ljubljana, league, Maribor, award, interview, concert, weekend, game;health measure, human, mask, virus, government, epidemic, Slovenia, infection, country, coronavirus, doctor, week, health, number, case, work, life, help, school;family child, year, human, school, life, woman, head, hand, parent, world, thank you, man, word, language, end, thing, mother, book, family;politics government, party, state, year, money, Slovenia, minister, media, president, election, work, salary, law, parliament member, human, Jan\u0161a, \u0160arec, court, politics;ideology Slovenia, country, human, year, Slovenian, nation, border, migrant, war, communist, government, Europe, Jan\u0161a, power, army, world, media, justice, leftist.In Table\u00a0A topic is defined by the probability distribution over words, and we provide the top most probable words for each topic. Each topic is assigned a shorthand label to adequately characterize it and to facilitate further analyses. We assigned the topic labels manually, on the basis of the most probable words, and by inspecting several tweets for each topic. The six detected topics are listed below:Figure\u00a0In this subsection we turn attention to the topic distribution per community. We focus just on the top four communities, already identified in Fig.\u00a0Figure\u00a0P and Q, is defined by the Jensen\u2013Shannon divergence Lin :\\documenC, at timepoint t. We denote by C across the five timepoints C changes over time by computing the distances between subsequent timepoints Ci and Cj by computing the distance between their cumulative distributions Let Results with the differences in topic distributions are in Table\u00a0The right-hand side of Table\u00a0Similarities between the communities in terms of topic distributions are consistent with the formation of super-communities. A super-community is a set of communities that are densely linked together by the external influence links, i.e., retweets tweets posted by the three communities.The three communities are very different in size and in their Twitter activities. Figure\u00a0Out of the six topics detected, we first consider the two prevailing topics, politics and ideology, taken together. Figure\u00a0The change of the government in Slovenia in 2020 coincides with the emergence of the Covid-19 pandemic. In Fig.\u00a0In contrast to the politics and ideology, the health topic draws relatively low number of unacceptable tweets. However, as the pandemic progressed, and increasingly more unpopular public measures were taken, so has the volume of unacceptable tweets increased.This paper concludes a trilogy on the analysis of a comprehensive Slovenian Twitter data corpus, from the 2018\u20132020 period. In the first part and in other languages (Zollo et\u00a0al."} +{"text": "In the published article, there was an error in affiliation 1. Instead of \u201cDepartment of Rare and Head and Neck Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.\u201d, it should be \u201cKey Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Department of Rare and Head and Neck Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.\u201d.In the published article, there was an error in author order. Instead of \u201cJun Cao, Mengdi Zhang, Bin Wang, Long Zhang, Meiyu Fang and Fangfang Zhou\u201d, it should be \u201cJun Cao, Mengdi Zhang, Bin Wang, Long Zhang, Fangfang Zhou and Meiyu Fang\u201d.In the published article, there was an error in corresponding author order. Instead of \u201cLong Zhang L_Zhang@zju.edu.cn; Fangfang Zhou zhoufangfang@suda.edu.cn; Meiyu Fang fangmy@zjcc.org.cn\u201d, it should be \u201cMeiyu Fang fangmy@zjcc.org.cn; Long Zhang L_Zhang@zju.edu.cn; Fangfang Zhou zhoufangfang@suda.edu.cn\u201d.The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "After publication of this work , we noteThe author(s) declare that they have no competing interests.AML designed and coordinated the study, YS oversaw mosquito collections, dissections and rearing, CP conceived and conducted PCR assays, data entry and data analysis, ND assisted with fieldwork design and statistical analysis, and SJL conceived of, and worked on the optimization of the PS-PCR assay."} +{"text": "Business and government sites are planned for later.In 2004 the Sausalito, California\u2013based Natural Capital Institute began developing the World Index for Social and Environmental Responsibility (WISER) to bring together the more than 1 million organizations working to improve environmental and human health. WISER has launched a website targeted specifically at nonprofits at WiserEarth provides tools and a platform for NGOs, funding sources, and individuals to network and develop awareness of each other\u2019s work. Individuals can post personal profiles, and NGOs are given space to build a web presence.Visitors can post events and job openings, or participate in discussion forums on such topics as holistic health, sustainable agriculture, and climate change. The website features 44 main areas of focus, termed \u201cportals,\u201d which are further subdivided into 372 more specific topics. Among the portals are agriculture and farming, greening of industry, fisheries, pollution, poverty eradication, and sustainable development. Each portal page links to organizations, users, resources, jobs, and events associated with that topic. The page devoted to organizations allows visitors to browse for information a number of ways including by country, type of organization , area of focus, and activity type .A news section features rundowns of the latest updates to the website, postings by the media and press center, new multimedia offerings, volunteer openings, and a calendar of upcoming events around the world. Each day the site spotlights a different portal, organization, resource, and event."} +{"text": "Drs. Speiser, Cerottini, and Romero correctlThe authors also point out that in their experience, they found that the majority of T cells generated with the heteroclitic Melan-A M26 peptide were tumor reactive, citing their studies in vitro , and in In our study , we anal"} +{"text": "Medicinal plants and culinary herbs have been used since ancient times. Essential oils (EO) are a mixture of numerous compounds, mainly terpenes, alcohols, acids, esters, epoxides, aldehydes, ketones, amines and sulfides, that are probably produced by plants as a response to stress . Their uEOs have been used in foods as flavoring, as well as preserving agents, due to antimicrobial and antioxidant properties. Their main active components are: thymol, carvacrol, eugenol, cinnamaldehyde and linalool , althougStudies on the biological activities of essential oils have become increasingly important in the search for natural and safe alternative preservatives and health promoters. Another relevant use of EOs is their incorporation as feed supplements: for ruminants to modify ruminal metabolism in order to mitigate methane and ammonia emissions and for in vitro antioxidant and antimicrobial properties of EOs [There is an abundance of scientific literature on the study of s of EOs ,6,12,13,s of EOs ,15 and ts of EOs ,16, or ts of EOs . Actual"} +{"text": "Dinib, Manzoor Hussaina, David Soleimani\u2010Meigoonib, and Ali S. MeigoonibShahid B. Awan,a Department of Physics, Jinnah Campus, Lahore, Pakistan;University of the Punjab,b Department of Radiation Medicine, Lexington, Kentucky, U.S.A.University of Kentucky,The institutional affiliation for co\u2010author Manzoor Hussain is missing. The affiliation of Manzoor Hussain is University of the Punjab, Department of Physics, Jinnah Campus, Lahore, Pakistan. With this correction, the institutional affiliations of all the authors will be as follows:ii)Pd103 source is shown in the following Table. It should be noted the graphical representation of the 2D\u2010aniotropy is does not need any correction.Table iii)On the legend of Fig. In this erratum, we present the corrections for three typographical errors that occurred in the above noted publication on pages 123, 130 and page 138, respectively."} +{"text": "Ishwar Chandramouliswaran was not included as an author in the published article. The authors apologize for this error and state that this does not change the content of the article.The original article has been updated.IH: Manuscript writing, figure design. TD, JK, AK, and WK: Manuscript and figure revision, approval of final manuscript. IH, TD, JK, IC, AK, and WK: Management and project support for Cancer Genomics Cloud Pilots.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The affiliation for the ninth author is incorrect. Muhammad Bashir Bello is not affiliated with #7 but with #6, Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia Serdang, Selangor, MalaysiaThere are errors in"} +{"text": "The institutional affiliation for co\u2010author Manzoor Hussain is missing. The affiliation of Manzoor Hussain is University of the Punjab, Department of Physics, Jinnah Campus, Lahore, Pakistan. With this correction, the institutional affiliations of all the authors will be as follows:a,b Sharifeh A. Dinib, Manzoor Hussaina, David Soleimani\u2010Meigoonib, and Ali S. MeigoonibShahid B. Awan,a Department of Physics, Jinnah Campus, Lahore, Pakistan;University of the Punjab,b Department of Radiation Medicine, Lexington, Kentucky, U.S.A.University of Kentucky,P103d source is shown in the following Table. It should be noted the graphical representation of the 2D\u2010aniotropy is does not need any correction.Table On the legend of Fig. In this erratum, we present the corrections for three typographical errors that occurred in the above noted publication on pages 123, 130 and page 138, respectively."} +{"text": "IJERPH focuses on maternal and child health (MCH), with research that highlights the role of environmental influences on MCH across a range of settings. Importantly, the issue focuses on a broad range of environments, including chemical, natural, built, and social. MCH encompasses health status and well-being of women, infants, children, adolescents, and their families. Their well-being determines the health of the next generation, and can help predict future public health challenges for families, communities, and the healthcare system. However, MCH racial, ethnic, and socioeconomic disparities in morbidity and mortality are significant problems worldwide. These differences are likely the result of many factors which are influenced by a variety of environmental factors, including concentrated poverty which increases exposure to environmental toxins [This Special Issue of l toxins , social l toxins , exposurl toxins ,4, neighl toxins , and insl toxins ,7,8. In l toxins . Income l toxins , and theEarly experiences are biologically and behaviorally embedded, impacting neurodevelopment and health long term ,14,15,16Several other papers focus on the importance of the social and physical environments, particularly with respect to childhood obesity prevention and treatment for malnutrition. During the last three decades, the U.S. obesity rate has doubled in adults and tripled in children and adolescents . The widThe papers within this issue demonstrate the worldwide concern regarding physical social and biological environmental influences on the health of the MCH population, with contributions from various points across the U.S., and from Australia to Pakistan, Japan, Taiwan, and China, and back to European countries, namely Poland, Italy and Austria. The wide range of issues illustrated in this issue confirm the public health seriousness of these environmental influences, as well as the timely publication of this Special Issue on Maternal and Child Health."} +{"text": "Future Science OA, 3(4), FSO246 (2017), there was a misspelling in affiliation 1. This was published incorrectly as: Department of Cardiology, Renming Hospital of Wuhan University, Wuhan 430060, PR China. The correct affiliation is: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.In the Review by, Peng Zhong & HE Huang, \u2018Recent progress in the research of cold-inducible RNA-binding protein\u2019, which appeared in October 2017 in Future Science OA would like to sincerely apologize for any inconvenience or confusion this may have caused our readers.The authors and editors of"} +{"text": "In the published article, there was an error in affiliation 38. Instead of \u201cFaculty of Social and Management Sciences, Adekunle Ajasin University, Akungba-Akoko, Nigeria,\u201d it should be \u201cDepartment of Pure and Applied Psychology, Adekunle Ajasin University, Akungba-Akoko, Nigeria.\u201d Also, the affiliation of F\u00edvia A. Lopes is \u201cLaboratory of Evolution of Human Behavior, Federal University of Rio Grande do Norte, Natal, Brazil\u201d instead of \u201cDepartment of Psychology, Faculty of Languages History and Geography, Ankara University, Ankara, Turkey.\u201dFahd A. Dileym was not included as an author in the published article. The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Eight authors were not included in the author byline and inadvertently listed only in the Acknowledgements. Please see the full list of added authors as well as an updated byline below:Jean-Baptiste Adrien should be listed as the eighth author and affiliated with Emergency Department of Hospital Center Basse-Terre, Basse-Terre, Guadeloupe, France. The contributions of this author are as follows: Substantial contribution to conception of clinical procedures and acquisition of data through patients care and filling in the study form in Guadeloupe, revising the article critically for important intellectual content, and final approval of the version to be published.Andr\u00e9 Cabi\u00e9 should be listed as the ninth author and affiliated with University Hospital Center Fort de France, Fort de France, Martinique, France. The contributions of this author are as follows: Substantial contribution to conception of clinical procedures and acquisition of data through patients care and filling in the study form in Martinique, revising the article critically for important intellectual content, and final approval of the version to be published.Stephanie Guyomard should be listed as the tenth author and affiliated with Institut Pasteur de Guadeloupe, Les Abymes, Guadeloupe, France. The contributions of this author are as follows: Substantial contribution to conception of the biological procedures and acquisition of data through blood samples analysis and interpretation of biological results in Guadeloupe, revising the article critically for important intellectual content, and final approval of the version to be published.Cecile Herrmann-Storck should be listed as the eleventh author and affiliated with University Hospital Center Pointe \u00e0 Pitre, Pointe \u00e0 Pitre, Guadeloupe, France. The contributions of this author are as follows: Substantial contribution to conception of the biological procedures and acquisition of data through blood samples analysis and interpretation of biological results in Guadeloupe, revising the article critically for important intellectual content, and final approval of the version to be published.Patrick Hochedez should be listed as the twelfth author and affiliated with University Hospital Center Fort de France, Fort de France, Martinique, France. The contributions of this author are as follows: Substantial contribution to conception of clinical procedures and acquisition of data through patients care and filling in the study form in Martinique, revising the article critically for important intellectual content, and final approval of the version to be published.Claude Olive should be listed as the thirteenth author and affiliated with University Hospital Center Fort de France, Fort de France, Martinique, France. The contributions of this author are as follows: Substantial contribution to conception of the biological procedures and acquisition of data through blood samples analysis and interpretation of biological results in Martinique, revising the article critically for important intellectual content, and final approval of the version to be published.Rafaelle Th\u00e9odose should be listed as the fourteenth author and affiliated with University Hospital Center Fort de France, Fort de France, Martinique, France. The contributions of this author are as follows: Substantial contribution to conception of the biological procedures and acquisition of data through blood samples analysis and interpretation of biological results in Martinique, revising the article critically for important intellectual content, and final approval of the version to be published.Isabelle Lamaury should be listed as the fifteenth author and affiliated with University Hospital Center Pointe \u00e0 Pitre, Pointe \u00e0 Pitre, Guadeloupe, France. The contributions of this author are as follows: Substantial contribution to conception of clinical procedures and acquisition of data through patients care and filling in the study form in Guadeloupe, revising the article critically for important intellectual content, and final approval of the version to be published.Additionally, Philippe Qu\u00e9nel should now be listed as the sixteenth author.Sylvie Cassadou1*, Jacques Rosine1, Claude Flamand1\u00a4, Martina Escher1, Martine Ledrans1, Pascale Bourhy2, Mathieu Picardeau2, Jean-Baptiste Adrien3, Andr\u00e9 Cabi\u00e94, St\u00e9phanie Guyomard5, C\u00e9cile Herrmann-Storck6, Patrick Hochedez4, Claude Olive7, Raphaelle Th\u00e9odose7, Isabelle Lamaury8, Philippe Qu\u00e9nel11 Interregional Epidemiology Unit for Antilles-Guyane, French Institute for Public Health Surveillance, Paris, France.2 Institut Pasteur, \"Biology of Spirochetes\" unit, National Reference Center and WHO Collaborating Center for leptospirosis, Paris, France.3 Emergency Department, Hospital Center Basse-Terre, Basse-Terre, Guadeloupe, France.4 Infectious Diseases Department, University Hospital Center Fort de France, Fort de France, Martinique, France.5 Institut Pasteur de Guadeloupe, Les Abymes, Guadeloupe, France.6 Microbiology Laboratory, University Hopital Center Pointe \u00e0 Pitre, Pointe \u00e0 Pitre, Guadeloupe, France.7 Microbiology Laboratory, University Hopital Center Fort de France, Fort de France, Martinique, France.8 Infectious Diseases Department, University Hospital Center Pointe \u00e0 Pitre, Pointe \u00e0 Pitre, Guadeloupe, France.\u00a4a Current address: Epidemiology Unit of Pasteur Institute of French Guiana, Cayenne, France \u00a4b Current address: Ecole des Hautes Etudes en Sant\u00e9 Publique, Laboratoire d'\u00e9tude et de recherche en environnement et sant\u00e9, Rennes, France."} +{"text": "The end of 2016 marked, among others, also an important cultural event, through its novelty and uniqueness, which took place at the oldest University of Medicine and Pharmacy in Romania. \u201cConstantin Brancusi\u201d vernissage of sculpture exhibition took place in the imposing Hall of Honor of \u201cCarol Davila\u201d University of Medicine and Pharmacy in Bucharest and was organized through the efforts of some culture enthusiasts, such as Constantin Barbu, Vice-president of \u201cMihai Eminescu\u201d International Academy in Craiova and the famous surgeon, Prof. Mircea Beuran, MD, PhD, the President of the Senate of \u201cCarol Davila\u201d University of Medicine and Pharmacy in Bucharest. The exhibition presented twenty sculptures of immortal Brancusi, which were lost in the passing of time, but have been brought to life by the famous Romanian sculptor, Rodion Gheorghita. \u201cStudy for vanity, A muse, Old man head, The fish, The portrait of a doorman, Danaida, Red-skins, The portrait of Victoria Vaschide, The kiss, Eve, The baroness, Gheorghe Lupescu, The portrait of Daniel Poiana, etc.\u201d, were made by master Rodion Gheorghita, through efforts which only he himself knows, having as model a picture.The vernissage was opened by Academician Ioanel Sinescu, Rector of \u201cCarol Davila\u201d University of Medicine and Pharmacy, in the presence of the leaders of the University. Students and professors in the University, art critics, mass-media representatives and also an art enthusiastic public, participated in the event. A very distinct and honorable presence was the one of Academician G\u00fcnter Stock, President of European Academies (ALLEA).Academician G\u00fcnter Stock graduated from the prestigious University of Medicine in Heidelberg, Germany, and has an extensive scientific activity, having published over 300 papers in highly rated journals, in different fields, such as Neurosciences, Pharmacology or Structural Biochemistry, extremely valuable papers, which have been cited for over 8000 times in ISI-Web of Science indexed journals. Moreover, he is a promoter of the values of the Romanian culture, being, at the same time, one of the supporters of the integral translation in German of the work of Dimitrie Cantemir, the collection of the already translated volumes being present, thanks to him, in the Library of the Academy in Berlin. After the opening, the participants admired the items exhibited and sculptor Rodion Gheorghita gave details regarding the difficulty of making the sculptures, whereas the organizers offered the participants a glass of champagne. Executive EditorProfessor Eng. Victor Lorin Purcarea, PhD."} +{"text": "GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388: 1545\u20136022016; \u2014In this Article, Simon I Hay, Sudha P Jayaraman, Thomas Truelsen, Reed J D Sorensen, Anoushka Millear, Giorgia Giussani, and Ettore Beghi should have been listed as authors. The funding statement for Simon I Hay has been added. These corrections have been made to the online version as of Jan 5, 2017."} +{"text": "This case study was based on a school where the Tier 1 Program of the Project P.A.T.H.S. was integrated into the formal curriculum. In this case study, an interview with the school principal, vice-principal, and social worker was conducted in order to understand their perceptions of administrative arrangements and issues in the school, implementation characteristics, program effectiveness, program success, and overall impression. Results showed that several positive school and classroom attributes were conducive to program success, including positive school culture and belief in students' potentials, an inviting school environment, an encouraging classroom environment, high involvement of school administrative personnel, and systematic program arrangement."} +{"text": "Dear Editor,6H11NOS2) is the biologically active isothiocyanate produced by the metabolism of glucoraphanin by the enzyme myrosinase butane] belongs to the isothiocyanate class of phytochemicals. Glucoraphanin, a glucosinolate precursor of SFN, is a glucosinolate found in cruciferous vegetables such as broccoli, cabbage, cauliflower, and kale. All glucosinolates are composed of a basic structure consisting of a \u03b2-D-thioglucose group, a sulfonated oxime group, and an amino acid-derived side chain. Glucosinolates are activated by enzyme-dependent hydrolysis to their respective isothiocyanates. SFN , antimiSFN shows a range of biological activities and health benefits in humans, has been found to be a very promising chemopreventive agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach, and bladder but also against cardiovascular and neurodegenerative diseases and diabetes . In thiThis work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (316006-5).The authors declare no conflict of interest"} +{"text": "AbstractPiper species are used for spices, in traditional and processed forms of medicines, in cosmetic compounds, in cultural activities and insecticides. Here barcode analysis was performed for identification of plant parts, young plants and modified forms of plants. Thirty-six Piper species were collected and the three barcode regions, matK, rbcL and psbA-trnH spacer, were amplified, sequenced and aligned to determine their genetic distances. For intraspecific genetic distances, the most effective values for the species identification ranged from no difference to very low distance values. However, Piperbetle had the highest values at 0.386 for the matK region. This finding may be due to Piperbetle being an economic and cultivated species, and thus is supported with growth factors, which may have affected its genetic distance. The interspecific genetic distances that were most effective for identification of different species were from the matK region and ranged from a low of 0.002 in 27 paired species to a high of 0.486. Eight species pairs, Piperkraense and Piperdominantinervium, Pipermagnibaccum and Piperkraense, Piperphuwuaense and Piperdominantinervium, Piperphuwuaense and Piperkraense, Piperpilobracteatum and Piperdominantinervium, Piperpilobracteatum and Piperkraense, Piperpilobracteatum and Piperphuwuaense and Pipersylvestre and Piperpolysyphonum, that presented a genetic distance of 0.000 and were identified by independently using each of the other two regions. Concisely, these three barcode regions are powerful for further efficient identification of the 36 Piper species. Piper have been used since prehistoric times for a variety of human activities. They are used as spices, in traditional and processed forms of medicines, in cosmetic compounds, in cultural activities and as insecticides to discriminate between bird species. MT-CO1, 16s RNA, MT-CYB and RNA 18s in 242 species of fish and in 11 Epinephelus species.Plants in the genus cticides . Piperbcticides . Eugenolcticides . Althougbacteria . InvestiThailand , 2009 ha for use . Medicin for use . It prinmatK gene , the rbcL gene regions identified by the Piper species as economically valued plants worldwide and with the plant parts of many species being used, such as the trunk, leaves and fruits, as well as young plants and processed plant materials in the forms of powder and slices, identifying the species used is paramount to verify the authenticity of such goods. Therefore, these products should have a specific marker that identifies a species using barcode for each species.The standard barcodes used for most investigations of plants are the three plastid barcodes, which include PageBreakPiper species in Thailand using matK, rbcL and the psbA-trnH spacer regions, as these species are important medicinal plants that have not been fully explored for barcode identification. Here we initiate the development of reference barcodes for plant parts, young plants and plant products.The aim of this research was to construct barcodes for Piper recently reported in Thailand (Species and sites of Thailand were colWhole genomic DNA was extracted using a Plant Genomic DNA Extraction Kit (RBC Bioscience) following the kit protocols. Polymerase chain reaction (PCR) analyses were performed with primer pairs (5'\u20133') ATCCATCTGGAAATCTTAGTTC and GTTCTAGCACAAGAAAGTCG consisted of 1\u00d7 GoTaq Green Master Mix (Promega), 0.5 \u00b5M primers, and 30 ng of DNA template. The amplification profile included pre-denaturation at 94 \u00b0C for 1 min, 35 cycles of denaturation at 94 \u00b0C for 30 s, annealing at 52 \u00b0C (for matK) or 55 \u00b0C (for rbcL and the psbA-trnH spacer) for 30 s, extension at 72 \u00b0C for 1 min and a final extension at 72 \u00b0C for 5 min. The amplified products were subjected to 2% agarose gel electrophoresis.GAAAGTCG for the CCACCRCG for the CACAATCC for the http://blast.ncbi.nlm.nih.gov/Blast.cgi). Sequences were aligned for each genome region amplified to determine genetic distance values PageBreakby MEGA6 . This may be because the DNAs were fragmented at the primer regions. Table matK, rbcL and psbA-trnH spacer regions for all 36 species studied.The amplification of barcode bands from the matK region, the lowest value of 0.000 was observed in Piperdominantinervium, Piperhongkongense, Piperkraense and Piperlongum, while the highest value of 0.386 was observed for Piperbetle; 2) for the rbcL region, the lowest value of 0.000 was observed in Piperdominantinervium, Piperhongkongense, Piperlongum, Piperpedicellatum, Piperpilobracteatum, Piperpolysyphonum, Pipersarmentosum, Pipersylvestre and Piperwallichii, while the highest value of 0.166 was observed in Piperbetle; 3) for the psbA-trnH spacer region, the lowest value of 0.000 was observed in Piperdominantinervium, Piperkhasianum, Piperkraense, Piperlongum, Pipermontium, Pipermutabile, Pipernigrum, Piperpilobracteatum, Piperpolysyphonum and Pipersarmentosum while the highest value of 0.117 was observed in Piperboehmeriifolium.The intraspecific genetic distances for each region were the following: 1) for the matK region the lowest value of 0.000 was observed in the paired species Piperkraense and Piperdominantinervium, Pipermagnibaccum and Piperkraense, Piperphuwuaense and Piperdominantinervium, Piperphuwuaense and Piperkraense, Piperpilobracteatum and Piperdominantinervium, Piperpilobracteatum and Piperkraense, Piperpilobracteatum and Piperphuwuaense and Pipersylvestre and Piperpolysyphonum, while the highest value of 0.486 was observed between Piperribesioides and Piperpilobracteatum; 2) for the rbcL region, the lowest value of 0.000 was observed between pairs Piperdominantinervium and Pipercaninum, Piperkraense and Piperboehmeriifolium, Pipermaculaphyllum and Piperkhasianum, Pipermagnibaccum and Piperkhasianum, Pipermagnibaccum and Pipercaninum, Pipermagnibaccum and Piperdominantinervium, Pipermontium and Piperkhasianum, Pipermontium and Pipermagnibaccum, Pipermutabile and Pipercaninum, Pipermutabile and Piperdominantinervium, Pipermutabile and Pipermagnibaccum, Pipernigrum and Pipercaninum, Pipernigrum and Piperdominantinervium, Pipernigrum and Pipermagnibaccum, Pipernigrum and Pipermutabile, Piperpedicellatum and Piperkhasianum, Piperpedicellatum and Pipermagnibaccum, Piperpedicellatum and Pipermontium, Piperpedicellatum and Piperpendulispicum, Piperpendulispicum and PageBreakPageBreakPipercaninum, Piperpendulispicum and Piperdominantinervium, Piperpendulispicum and Pipermagnibaccum, Piperpendulispicum and Pipermutabile, Piperpendulispicum and Pipernigrum, Piperphuwuaense and Pipercaninum, Piperphuwuaense and Piperdominantinervium, Piperphuwuaense and Pipermagnibaccum, Piperphuwuaense and Pipermutabile, Piperphuwuaense and Pipernigrum, Piperphuwuaense and Piperpedicellatum, Piperpilobracteatum and Pipercaninum, Piperpilobracteatum and Pipermutabile, Piperpolysyphonum and Piperkhasianum, Piperpolysyphonum and Pipermagnibaccum, Piperpolysyphonum and Pipermontium, Pipersarmentosum and Piperlongum, Pipersylvestre and Piperkhasianum, Pipersylvestre and Pipermagnibaccum, Pipersylvestre and Pipermontium, Piperthomsonii and Pipernigrum, Piperpilobracteatum and Piperphuwuaense, Piperpolysyphonum and Piperpendulispicum, Piperpolysyphonum and Piperpedicellatum, Pipersylvestre and Piperpendulispicum, Pipersylvestre and Piperpedicellatum, Pipersylvestre and Piperpolysyphonum, Piperwallichii and Piperumbellatum, Piperprotrusum and Piperphuwuaense, and Piperprotrusum and Piperpilobracteatum, while the highest value of 0.213 was observed in the Piperbetle and Piperargyritis pair; 3) for the psbA-trnH spacer region the lowest value of 0.000 was observed in the pairs of Pipermontium and Pipermagnibaccum, Piperpilobracteatum and Pipercaninum, Piperpolysyphonum and Piperpedicellatum, Piperribesioides and Piperpedicellatum, Pipersarmentosum and Piperlongum, Pipersylvestre and Piperpedicellatum, Piperwallichii and Piperkhasianum, Piperwallichii and Piperpedicellatum, Piperprotrusum and Pipermagnibaccum, Pipersylvestre and Piperpolysyphonum, Pipersylvestre and Piperribesioides, Piperwallichii and Piperpolysyphonum, Piperwallichii and ribesioides, Piperwallichii and Pipersylvestre, and Piperyinkiangense and Piperbetle, while the highest value of 0.228 was observed between Pipersemiimmersum and Piperumbellatum.The interspecific genetic distances for each region were the following: 1) for the matK region in Table The genetic distance of the Piper in Thailand have many functional uses. Only four species, Piperbetle, Piperretrofractum, Pipernigrum and Pipersarmentosum are economic and cultivated species, and all of these species are also used as ingredients in the products mentioned above in the introduction. Piperbetle is a well-known species that is important for its chemical substances, including essential oils, chavicol, cineol and eugenol, which can be used for medicinal and insecticidal purposes. Because these plants are widely used, and used in several forms, which include plant parts, powdered preparations, capsule formulations and other preparations, their authenticity should be verified using DNA barcodes to establish the worthiness of these products for medicinal, cosmetics and house-hold use. To overcome the problems associated with identifying species based on morphological characters, DNA barcoding has been employed. For flowering plants in Thailand, the psbA-trnH spacer region was suggested as an efficient DNA barcode marker in Senna species (Smilax and Cissus species (rbcL gene has been suggested as a marker in parasitic plants, including Scurrula, Dendrophthoe, Helixanthera, Macrosolen and Viscum species (matK gene marker was identified in some medicinal Piper species (Piper species.Most of the 43 species of wild species , as well species . In addi species and the species . TherefoPageBreakPageBreakPiper species using three different marker regions support a previous hypothesis of genetic distance values (Piperbetle had the highest intraspecific genetic distance values of 0.386 for the matK region, which may have been due to the presence of human growth factors. The interspecific genetic distances for the matK region were effective for the identification of different species with 27 pairs of species ranging from a low of 0.002 to a high of 0.486, as shown in Table matK had high species identification reliability and suggested that this region should be used for identification of Piper species along with the ITS region. Additionally, the rbcL and psbA-trnH spacer regions are effective for further identification of the other eight species pairs as shown in Table Pipersylvestre and Piperpolysyphonum to the highest value 0.129 for the pair Piperphuwuaense and Piperkraense in psbA-trnH spacer region. It can be concluded that these three barcode regions are powerful for further efficient identification of the 36 Piper species.The results from DNA barcoding 36 e values , showingmatK and the psbA-trnH spacer to identify Myristicaceae plants, rbcL and matK as the core DNA barcode regions for land plants.The results presented here support those of"} +{"text": "Journal of Applied Clinical Medical Physics, and in 2008, with the publication of Volume 9, I began my term. I accepted the position with a personal goal of serving for five years. With the conclusion of Volume 13, I have now served five years, so the time has come for me to step down and provide the JACMP with an opportunity for fresh leadership.In 2007, I was invited to serve as the Editor\u2010in\u2010Chief of the JACMP, that I would be stepping down at the conclusion of 2012, with the intention of staying on for at least a year after management of the JACMP was taken over by the American Association of Physicists in Medicine (AAPM), to effect a smooth transition. After a nationwide search for a new Editor\u2010in\u2010Chief, the AAPM recently appointed Dr. Michael Mills to replace me. Many of you remember Dr. Mills as the previous Editor\u2010in\u2010Chief of the JACMP.Anticipating the end of my term, over a year ago I notified the American College of Medical Physics, the organization that sponsored the JACMP into an international journal. We have added two key organizations as sponsors: the Canadian Organization of Medical Physicists and the International Organization of Medical Physics, along with the addition of several Associate Editors nominated by these two organizations. Consequently, we now have a much broader reader base, as well as a much broader author base than we had previously. A second accomplishment has occurred in conjunction with the AAPM in that many JACMP articles are now available online on the AAPM website, so that medical physicists can obtain continuing education credits. Finally, we have experienced major growth in the JACMP with not only a greater number of submissions during the past five years for Volume 13 include the following: Nzhde Agazaryan, Salahuddin Ahmad, John Antolak, Pat Cadman, John Bayouth, Charles Bloch, Pat Cadman, Marco Carlone, Nathan Childress, Laurence Court, Luca Cozzi, Mini Das, Larry DeWerd, Bill Erwin, Vladimir Feygelmann, Kent Gifford, Ed Jackson, Jennifer Johnson, Tommy Kn\u00f6\u00f6s, Stephen Kry, Rajat Kudchadker, Harish Malhotra, Pietro Mancosu, Osama Mawlawi, Charles Mayo, Moyed Miften, Mike Mills, Eduardo Moros, Firas Mourtada, Ben Nelms, Jennifer O'Daniel, Niko Papanikolaou, Donald Peck, Matt Podgorsak, Joann Prisciandaro, Jim Rodgers, John Rong, Yi Rong, Isaac Rosen, Surendra Rustgi, Narayan Sahoo, Bill Salter, Mehrdad Sarfaraz, Jeff Shepard, Chengyu Shi, Alf Siochi, Eric Slessinger, Jason Stafford, Lu Wang, Chuck Willis, Kamil Yenice, Geoffrey Zhang, and Ronald Zhu.Thank you to our Associate Editors and our reviewers, and especially to our authors, without whose contributions we would have no journal. My best wishes go to my successor, Dr Mills.George Starkschall, PhDEditor\u2010in\u2010ChiefSupplementary Material FilesClick here for additional data file.Supplementary Material FilesClick here for additional data file."} +{"text": "This was an international study of women's health issues, based on an Official Study Tour in Southeast Asia and Canada. The objectives of the study were to identify and compare current gaps in surveillance, research, and programs and policies, and to predict trends of women''s health issues in developing countries based on the experience of developed countries. Key informant interviews , self-administered questionnaires, courtesy calls, and literature searches were used to collect data. The participating countries identified women's health as an important issue, especially for reproductive health (developing countries) and senior's health (developed countries). Cancer, lack of physical activity, high blood pressure, diabetes, poverty, social support, caring role for family, and informing, educating, and empowering people about women's health issues were the main concerns. Based on this study, 17 recommendations were made on surveillance, research, and programs and policies. A number of forthcoming changes in women's health patterns in developing countries were also predicted."} +{"text": "In the published article, there was an error in affiliation (2). Instead of \u201cMicrobiology and Micology Program, Faculty of Medicine, University of Chile, Santiago, Chile,\u201d it should be \u201cMicrobiology and Micology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.\u201d The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.Additionally, there was an error regarding the affiliations for Yalda Lucero. Affiliation 8 has been removed and the following affiliation has been added instead: Pediatric Gastroenterology Unit, Department of Pediatrics, Cl\u00ednica Alemana-Universidad del Desarrollo, Santiago, Chile.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Yiqiang Yuan and Qiangsun Zheng, the seventh and eighth authors, respectively, should be indicated as being Corresponding Authors for the article. Both of the authors share the same email address as the Corresponding Author already indicated. In addition, the affiliation for the fifth author is incorrect. Yujie Zhao is not affiliated with institution number 1, but with institution number 2, Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi\u2019an."} +{"text": "Nature Communications, 10.1038/s41467-017-02480-6, published online 08 February 2018Correction to: https://github.iu.edu/kzhu/assembltrie, which links to a page that is not publicly accessible. The source code is publicly accessible at https://github.com/kyzhu/assembltrie. Furthermore, in the PDF version of the Article, the right-hand side of Figure 3 was inadvertently cropped. These errors have now been corrected in both the PDF and HTML versions of the Article.The original version of this Article contained errors in the affiliations of the authors Ibrahim Numanagi\u0107 and Thomas A. Courtade, which were incorrectly given as \u2018Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720, USA\u2019 and \u2018Computer Science & Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA\u2019, respectively. Also, the hyperlink for the source code in the Data Availability section was incorrectly given as"} +{"text": "Escherichia coli (EHEC) ever reported. Four years thereafter, we systematically searched for scientific publications in PubMed and MEDPILOT relating to this outbreak in order to assess the pattern of respective research activities and to assess the main findings and recommendations in the field of public health. Following PRISMA guidelines, we selected 133 publications, half of which were published within 17\u2009months after outbreak onset. Clinical medicine was covered by 71, microbiology by 60, epidemiology by 46, outbreak reporting by 11, and food safety by 9 papers. Those on the last three topics drew conclusions on methods in surveillance, diagnosis, and outbreak investigation, on resources in public health, as well as on inter-agency collaboration, and public communication. Although the outbreak primarily affected Germany, most publications were conducted by multinational cooperations. Our findings document how soon and in which fields research was conducted with respect to this outbreak.In 2011, Germany experienced one of the largest outbreaks of entero-hemorrhagic Escherichia coli (EHEC) ever reported, almost 3,000 people fell ill with acute gastroenteritis, 855 of them developed hemolytic uremic syndrome (HUS). In total, 55 people died due to the infection , the German federal public health institute, together with local and state health and food safety agencies, conducted a total of 13 epidemiological field investigations, using different study designs. Initial investigations pointed at lettuce, raw tomatoes, and cucumbers as potential sources of the infection. On June 10\u20143 weeks after the first notification of the outbreak\u2014epidemiological evidence supported that fenugreek sprouts, produced in Germany from seeds imported from Egypt, were the vehicle causing the outbreak guidelines , we searBy applying the search criteria, we found 346 publications in PubMed and 304 in MEDPILOT; 214 articles (32.9%) were duplicates, resulting in a total of 436 unique publications written in Chinese, Dutch, English, French, German, Polish, Russian, Spanish, or Swedish. Of these, 255 publications were excluded based on content criteria, 47 for being editorials, commentaries, replies, diaries, or meeting abstracts, and five because of being submitted or published before May 1, 2011, leaving 129 (29.6%) after full-text screening. We identified an additional 11 publications on scrutinizing reference lists of eligible reviews, of which four articles fulfilled our eligibility criteria. In total, 133 eligible publications were included in the systematic review contributed to the study design, interpretation of the data, and to the writing and revision of this paper. All authors agree to be accountable for the content of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Hyssopus, Leonurus, Mentha, Nepeta, Origanum, Perovskia, Phlomis, Salvia, Scutellaria, and Ziziphora are widespread throughout the world, are the most popular plants in Uzbek traditional remedies, and are often used for the treatment of wounds, gastritis, infections, dermatitis, bronchitis, and inflammation. Extensive studies of the chemical components of these plants have led to the identification of many compounds, as well as essentials oils, with medicinal and other commercial values. The purpose of this review is to provide a critical overview of the literature surrounding the traditional uses, ethnopharmacology, biological activities, and essential oils composition of aromatic plants of the family Lamiaceae, from the Uzbek flora.Plants of the Lamiaceae family are important ornamental, medicinal, and aromatic plants, many of which produce essential oils that are used in traditional and modern medicine, and in the food, cosmetics, and pharmaceutical industry. Various species of the genera The Republic of Uzbekistan is located in the center of Eurasia. About 85% of its territories are deserts, and about 15% are mountains and foothills. The Uzbek flora accounts for approximately 4350 species of vascular plants, including large numbers of endemic, endangered, and globally important species. Plants endemic to Uzbekistan constitute 20% of all plants; and a majority of these grow in the mountains. The floristic data for several regions of Uzbekistan is imperfect, and studies are continuing . The. TheLeongenol 30.3%, p-vinLeonurus turkestanicus V. I. Krecz & Kuprian is a perennial shrub that grows in the plains and highlands of Asia on stony, shallow-soiled slopes, floodplains, streamsides, and among trees and other shrubs ..LeonurusMentha L. (mint) is a well-known genus due to its medicinal and aromatic value. It is represented by about 19 species and 13 natural hybrids, mainly perennial herbs, which grow wildly in damp or wet places throughout the temperate regions of Europe, Asia, Africa, Australia, and North America. Species of the genus Mentha have been reported to contain a range of components, including cinnamic acids, flavonoids, and steroidal glycosides. However, the main active component of the genus Mentha is essential oil, which is reported to govern its various properties ..Mentha LNepeta L. comprises perennial or annual herbaceous, small shrubs, and rarely includes trees. It is comprised of more than 200 species. This genus has a widespread distribution in the temperate regions of Asia, Europe, and North Africa. Some Nepeta species are widely used in traditional medicine, due to their diuretic, antispasmodic, anti-asthmatic, febrifuge, emmenagogue, sedative, and antiseptic properties ..Nepeta LNepeta olgae Regel grows as an aromatic perennial plant in the foothills and lowlands of the Syrdaya region, Kyzylkum, and the Surkhan-Sherabad and Ferghana Valleys ..Nepeta oOriganum L. consists of 43 species and 18 hybrids; most of which are distributed through the eastern Mediterranean region ..PerovskiPhlomis L. consists of 75 species of perennial shrubs, occurring from the Mediterranean to Central Asia. In Uzbekistan, the genus Phlomis is represented by 15 species. Phlomis thapsoides Bunge is a perennial herb growing wild in western Pamir-Alay. The aerial parts of this species are used in some areas of Asia for feeding animals, and to dye wool and silk ..Salvia LSalvia sclarea L. (clary sage) is a well known aromatic plant, from which an oil used to be produced in large quantities in the former Soviet Union. Apart from the various medicinal uses, the essential oils of clary sage are widely applied in the food and cosmetic industries, wine making. and as a tobacco flavouring agent ..Salvia sScutellaria L. includes about 350 species, commonly known as skullcaps ..ScutellaScutellaria ramosissima Popov is native to Uzbekistan and grows in Northern Tien Shan, Pamir-Altay mountains , on the midlands of the high-altitude belt. In Uzbek folk medicine, water extracts (tea and infusion) of S. ramosissima are widely applied for epilepsy, inflammation, allergies, and nervous tension. The bioactivity of the plant is most likely due to the major components: flavonoids. The chloroform extract of S. ramosissima showed potent cytotoxic effects to Trypanosoma brucei TC221, and HeLa, HepG-2, and MCF-7 cancer cells ..ScutellaZiziphora are annuals or perennials, and herbaceous or sub-shrubs. The world population of this genus is represented by more than 30 different species. The Ziziphora species are rich in flavonoids, caffeic acid derivatives, fatty acids, triterpenes, and sterols. The essential oils of Ziziphora have been well studied ..ZiziphorPlant species from the Lamiaceae family have been used in herbal medicine for thousands of years. Traditional applications of the Lamiaceae family show high applicability as a common tea, flavours, insect repellant, in flu control, and as an anti-inflammatory, sedative, and analgesic. Mainly essential oils, terpenoids, phenolic compounds, flavonoides, and iridoids, have been reported from the members of this family. Many of the medicinal uses are presumed to be connected to the terpenic constituents of the essential oils of these plants.Hyssopus seravschanicus, Leonurus panzerioides, L. turkestanicus, Mentha longifolia var. asiatica, Nepeta alatavica, N. olgae, Origanum tyttanthum, Perovskia scrophulariifolia, Phlomis thapsoides, Salvia korolkovii, S. sclarea, Scutellaria immaculata, S. ramosissima, S. schachristanica, Ziziphora clinopodioides, and Z. pedicellata, has also been presented. The available literature showed that most of the bioactivities and medicinal properties of these species could be attributed to their essential oils, which contain a variety of functional bioactive compounds, known to have applications in the food, feed, pharmaceutical, and cosmetic industries.The present review provides, for the first time, an updated compilation of the documented ethnopharmacological information in relation to the ethnomedicinal, ethnobotanical, phytochemistry, and biological activities of 16 aromatic and medicinal plants from the Lamiaceae family of the Uzbek flora. Information on their traditional medicinal uses, and the compounds identified in the essential oils obtained from"} +{"text": "Withania somnifera (WS) also known as ashwagandha is a well-known medicinal plant used in traditional medicine in many countries for infertility treatment. The present study was aimed at systemically reviewing therapeutic effects of WS on the reproductive system. This systematic review study was designed in 2016. Required data were obtained from PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of Knowledge, Web of Science, and manual search of articles, grey literature, reference checking, and expert contact. WS was found to improve reproductive system function by many ways. WS extract decreased infertility among male subjects, due to the enhancement in semen quality which is proposed due to the enhanced enzymatic activity in seminal plasma and decreasing oxidative stress. Also, WS extract improved luteinizing hormone and follicular stimulating hormone balance leading to folliculogenesis and increased gonadal weight, although some animal studies had concluded that WS had reversible spermicidal and infertilizing effects in male subjects. WS was found to enhance spermatogenesis and sperm related indices in male and sexual behaviors in female. But, according to some available evidences for spermicidal features, further studies should focus on the extract preparation method and also dosage used in their study protocols. Infertility is a complicated problem with physiologic, psychologic, and economic aspects. Infertility is defined as the inability to conceive after one year of unprotected sexual intercourse . About 1The causes of male infertility are classified as pretesticular, testicular, posttesticular, and unknown. Sperm abnormality causes 30%\u201340% of all infertility . PretestDifferent etiologies of female infertility include ovarian diseases, tubal disorders, endometriosis, uterine pathologies, cervical problems, congenital anomalies, and dysfunction of the hypothalamus-pituitary-ovarian axis and systemic diseases , 9. TreaWithania somnifera, (WS) also known as ashwagandha, Indian ginseng, winter cherry, horse smell, Kaknaje Hindi, is a well-known medicinal plant in Solanaceae family used in traditional medicine in many countries such as Iran and India [nd India . This plnd India , 13. Thind India , 15. Difnd India \u201318. Manynd India .WS has been recommended for management of polyarthritis, lumbago, painful swellings, premature ejaculation, oligospermia, plague, asthma, vitiligo, general debility, impotency, ulcers, uterine infection, leucorrhoea, hemorrhoid, and orchitis in traditional Persian medicine , 61. AllWithania somnifera\u201d , \u201cfertility\u201d, \u201cconceive\u201d, \u201cinfertility\u201d, \u201cwomen\u201d, \u201cmen\u201d, \u201cfemale\u201d, \u201cmale\u201d, \u201csemen\u201d, \u201csperm\u201d, \u201cspermicidal\u201d, \u201cSertoli\u201d, \u201cprolactin\u201d, \u201cfollicular stimulating hormone\u201d, \u201cluteinizing hormone\u201d, \u201ctestosterone\u201d, \u201clibido\u201d, \u201caphrodisiac\u201d, \u201cbehavior\u201d, \u201csexual\u201d, \u201cspermatogenesis\u201d, \u201creproduction\u201d, \u201csemenogogue\u201d, \u201cimpotency\u201d, \u201cspermatozoa\u201d, \u201cestrogen\u201d, \u201cpregnancy\u201d, \u201cgonadotropin releasing hormone\u201d, \u201ctestis\u201d, \u201cleydig\u201d, and \u201covarian\u201d. The time period between 1965 and 2017 was selected. Also, to increase the scope of the study, manual search in some of the valid journal databases was performed. All in vitro or in vivo studies about the effects of WS on reproductive system and fertility among human or animal subjects were included in the study. Review studies, case reports, letter to editors, and short communications were excluded from the study.In this systematic review which was performed in 2016, required data were gathered using databases such as Google Scholar, PubMed, Scopus, Web of Science, and Cochrane Library. The keywords used in present study were \u201cTo search for unpublished articles (grey literature), European Association for Grey Literature Exploitation (EAGLE) and Health Care Management Information Consortium (HMIC) were searched.The selected papers extracted from the databases were assessed by two investigators using Consort 2010 checklist. Discrepancies between the two raters were referred to the third investigator. First, the titles of all articles were reviewed to screen for eligibility and those found to be irrelevant with the objectives of the study were excluded from the study. In the later stages, the abstracts and full-text articles were, respectively, examined to identify and exclude those that did not match the inclusion.One reviewer extracted the data from the included studies while a second author checked the results. Any disagreements were resolved by a discussion of reviewers. Data for the primary objective of the review was collected from the full text of each publication and included the trial name, year of publication, type of study, sample size, results, and other characteristics.Statistical analysis was performed by SPSS software package version 16.0 for windows . QuantitThe flowchart of the study is shown in Many phytochemicals have been extracted from WS, which includes alkaloids, flavonoids, steroidal lactones, saponins, neurotransmitters, essential and nonessential fatty acids, ergostane, and gamma amino butyric acid; of all these components, alkaloids, and withanolids such as withaferin A, withanosides, sitoindosides, beta-sitosterol, and various amino acids like alanine have more prominent effect on fertility status , 51, 55.In animal studies, WS is known to have gonadotropic function which increases gonadal weight by growthing follicles size in female and also increasing seminiferous tubular cell layers in male animals , 57\u201359. In a study by Shukla et al. about effects of WS on men, WS root powder was used for 3 months and it was shown that sperm parameters such as count and motility in sperm analysis had improved due to decrease apoptosis and reactive oxidative stress among men with normospermia and oligospermia; also copper, zinc, iron, and gold ions of seminal plasma had increased after the treatment and subsequently semen quality increased. This increase in semen quality is proposed to be due to the increase in essential neurotransmitters, metallothionein which has antioxidative function, and metal ions as cofactors for essential enzymes .In two clinical trials, the effects of 5 grams of WS root for 3 months on semen parameters of infertile men were investigated. Improvement in semen quality, increased vitamins E, C, and A, and increased fertility were reported which is proposed to be due to the high amount of alkaloids, ergostane steroids, and essential amino acids in WS which improved detoxification, decreased oxidative stress, and restorated testosterone secretion , 25.In another human study, treatment by WS aqueous extract in married healthy women increased their sexual function index and diminished sexual distress index statistically significant . In two In a study by Bhattarai et al. about effects of WS root extract, it was found that GABA mimetic features of this extract led to an increased activity of gonadotropin releasing hormone secreting neurons . On the Prabu et al. in a study on male rats found that hydroalcoholic WS root extract was found to decrease white blood cell and lymphocyte counts in blood, but no considerable effect on reproductive indices . AlcoholWS leaves and roots have been found to improve oxidative stress indices such as an increase in superoxide dismutase, catalase, glutathione, lactate dehydrogenase, alanine, glutamine, phenylalanine, and decrease in cortisol and fructose , 51, 58. Nile tilapia, it was found that this extract with androgenic effects decreased prolactin level and estrogen level by inhibiting aromatase activity and induced male phenotype formation; this phenomenon was proposed to be due to components such as tannin, saponins, terpenoids, steroids, and flavonoids [In a study investigating effects of 6.5\u2009mg of WS root extract onavonoids .Traditional and complementary medicine have been more popular nowadays to cure health related conditions . This prWithania somnifera is one of the herbal medicines widely used for the treatment of infertility and sexual dysfunction. This plant has been known to contain more than 80 types of phytochemicals such as steroidal and nonsteroidal alkaloids, steroidal lactones and saponins like isopelletierine, anaferin, anahygrine, hygrine, cuscohygrine, tropine, pseudotropine, withananine, ashwagandha, withaferins, withananinine, pseudowithanine, somnine, somniferine, somniferinine, 3-tropyltigloate, withanine, withasomine, visamine, mesoanaferine, sitoindoside (7\u201310), hentriacontane, amino acids such as aspartic acid, glycine, tryptophan, proline, alanine, tyrosine, hydroxyproline valine, cystine, glutamic acid, and cysteine, calcium, phosphorus, iron, flavonoids, starch, reducing sugars, proteolytic enzyme \u201cchamase,\u201d glycosides, dulcitol, and volatile oil. Of all these components, withaferin A and sitoindosides had the key role in WS therapeutic effects [ effects , 61, 72.Based on the present study, it was shown that extracts of WS fruits, leaves, stems, and especially roots enhance sperm quality indices such as motility and count in men , 24, 25 The mechanism of WS effect on the reproductive system is not known entirely yet, but this mechanism is proposed to be linked to the antioxidative features and ability to improve the hormonal balance of LH, FSH, and testosterone and improve detoxification process. Also, the GABA mimetic feature of WS extract is thought to play the main role in inducing gonadotropin releasing hormone secretion and improving hormonal balance , 47, 51. Withania somnifera has a positive effect in the treatment of infertility both in male and female. Although some studies proposed that WS extract might have infertilizing and spermicidal effect. Due to the growing interest in using herbal medicine especially those which possess the antioxidative and reproductive system supporting properties, further studies are needed to be designed with higher population and more-structured methodology so a more precise and decisive conclusion can be made.Based on the results, it deems that"} +{"text": "This sentence should appear as:In the article, \u201cMesalazine as a cause of fetal anemia and hydrops fetalis: A case report\u201d,According to the SweidshMedical Birth Register 1302 pregnancies were reported exposed to sulfasalazine between 1973 and 2012, and 2072 to mesalazine, but these numbers may be underestimated.The corresponding address should appear as Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden."} +{"text": "STK32B (serine/threonine kinase 32B), rs17590046 in PPARGC1A , and rs12764057, rs10822974, and rs7903491 in CTNNA3 , were found to be associated with increased risk of essential tremor (ET) in a genome-wide association study (GWAS)in individuals of Caucasian ancestry. Considering the overlap between ET and Parkinson's disease (PD) in pathological features and clinical manifestations, a case-control study comprising 546 PD patients and 550 control subjects was carried out to examine whether the same variants were also associated with PD in Chinese Han population. However, the above variants did not show an association with PD. Our results suggested that these variants do not play a major role in PD in the Chinese population, Actually, the clinical overlap between PD and ET is under debate. In our Chinese Han cohort, we did not verify potential genetic pleiotropy between two diseases, which may indicated that etiology and pathobiology of PD and ET are distinct. Thus, a more comprehensive study such as a multi-center study may be helpful to evaluate the relationship between the five new susceptible loci and PD in Chinese Han population in the future.Recently, five novel single nucleotide polymorphisms (SNPs), rs10937625 in Parkinson's disease (PD) is the second most common neurodegenerative disorder, and affects approximately 1.7 million individuals (aged \u2265 65 years) in China , 3.SNCA, GBA, and LRRK2 have been reported to be associated with the risk of PD (STK32B (serine/threonine kinase 32B), rs17590046 in PPARGC1A have been identified, and are significantly associated with increased risk of ET in individuals of Caucasian ancestry (LINGO1 variant has been implicated in etiologic links between ET and PD (Genome-wide association study (GWAS) is a powerful tool for genetic association studies, many GWAS-related polymorphic loci, such as single nucleotide polymorphisms (SNPs) in sk of PD \u20138. Recenancestry , and indT and PD . MoreoveT and PD \u201316. ThusConsequently, a case-control study comprising 546 PD patients and 550 healthy controls was performed to investigate the association between the five new loci and PD in Chinese Han population. In fact, similar studies have been published in two independent groups , 18, andAs shown in Table P > 0.05) in the control group , rs10822974 , rs10937625 , rs7903491 , rs17590046 and PD in our Chinese Han cohort , in Asian patients , which regulates mitochondrial biogenesis and expression of many antioxidant genes, plays an important role in protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity :This study doesn't intervene the whole process of diagnosis and treatment, and doesn't affect the patients medication such as diagnosis and treatmentInformed consent of subjects was obtained from all the subjects, and explain the purpose and significance of research to themWe will never give patient information to others, anonymously to the statistics, and the research will bring benefits to diagnosis and treatment, but the subjects will not take on additional risk.JY, YC, CS, and YX: The conception or design of the work; JY, YC, MT, ZY, FL, YF, CS, and YX: Drafting the work or revising it; JY, YC, MT, ZY, FL, YF, CS, and YX: Final approval of the version to be published; JY, YC, MT, ZY, FL, YF, CS, and YX: Agreement to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the paper, by the Fa\u00e0 di Bruno formula, the authors establish two explicit formulas for the Motzkin numbers, the generalized Motzkin numbers, and the restricted hexagonal numbers. For detailed information, please refer to [The first seven Motzkin numbers entclass1pt{minimanographs , the surnographs , and theIn , the \\doshown in , Theoremomparing with , , \\documeirtue of , it follanged as .Letting vely, in and consvely, in lead to vely, in and in can be ekk!}. By once agaequation follows.Taking vely, in and consvely, in lead to vely, in , 1.12),,\\documenvely, in readily.t}$=,1$\\end{dFinally, we list several remarks.The explicit formula is a genEquation and manymentclasspt{minimafound in and the By the second relation in , equatioquations and ,,1.11), aBy the Fa\u00e0 di Bruno formula and some properties of the Bell polynomials of the second kind, we establish two explicit formulas for the Motzkin numbers, the generalized Motzkin numbers, and the restricted hexagonal numbers."} +{"text": "Prosodic Parallelism hypothesis claims adjacent prosodic categories to prefer identical branching of internal adjacent constituents. According to Wiese and Speyer (The d Speyer , this pr Language is manifested in a spoken and in a written modality . Final in the German orthography is usually pronounced [\u04d9], the central short vowel called nouns: T\u00fcr(e) \u2018door\u2019, Aug(e) \u2018eye\u2019, Ruh(e) \u2018quietness\u2019inflected nouns, gen. sg.: Sturm(e)s, \u2018storm\u2019, Jahr(e)s \u2018year\u2019adjectives/adverbs: b\u00f6s(e) \u2018bad\u2019, bang(e) \u2018afraid\u2019, nah(e) \u2018near\u2019, gern(e) \u2018gladly\u2019, heut(e) \u2018today\u2019verbs: (1st ps. sg.): hab(e) \u2018have, present tense\u2019, seh(e) \u2018see, present tense\u2019prepositions: ohn(e) \u2018without\u2019(1) Schwa-/zero alternationsgern and gerne \u2018gladly\u2019 occur with high frequency across Standard German variants, although the latter form was found to be twice as frequent in written German by Wiese and Speyer Determiner noun combinationsT\u00fcr happens to be much more frequent than T\u00fcre), the frequencies of the preferred combinations should be higher than expected from the combination of the frequencies of the two parts. Formulating the hypothesis in this way, it is testable, because present-day corpora of German contain the required combinations of words in sufficiently large numbers. Note that the combination of the noun with the two determiners provides the kind of minimal pair needed for the test of the hypothesis: there are two surface phrases with very similar meaning. All cases discussed below share this property.More precisely, given the independently existing frequencies of the determiner forms and the alternating noun forms as presented in (2) as well as for a large range of other words and phrases summarized in (3).Wiese and Speyer drew upo(3) Statistical tests for Prosodic Parallelism; results from Wiese and Speyer des/eines Jahr(e)s, dem/einem Tag(e), and sehr/richtig gern(e), the significant effects actually pointed into the direction opposite to what was predicted. One reason for these counter-examples might be that the prosodic phrasing is actually not the one assumed in the paper: dative noun phrases as in (3) predominantly appear within prepositional phrases, for which the prosodic phrasing may be as in [[an dem] [Tag(e)]] \u2018at the day\u2019. For more discussion of these real or apparent counter-examples see Wiese and Speyer gern(e), the test does not apply to a phrase consisting of two words, but to a complex word consisting of two morphemes. However, there is evidence that such prefix-stem combinations consist of two phonological words; see, e.g., Wiese ((un)gern(e), with main stress on the prefix, probably does not differ in prosody from the small phrases provided by the other examples in terms of prosodic structure.For further tests of the Prosodic Parallelism hypothesis in the spoken mode, initially all phrases from the study by Wiese and Speyer were sel., Wiese . In othedie, der/eine, einer + T\u00fcr(e) \u2018the, a + door, nom./acc. vs. gen./dat.\u2019des/eines + Tag(e)s \u2018the/a + day, gen. sg.\u2019des/eines + Jahr(e)s \u2018the/a + year, gen. sg.\u2019(un) + gern(e) \u2018(not) + gladly\u2019bin, war, ist, sind, seid / waren, seien, werden, wurde, wurden + nah(e) \u2018am, was, is, are, are /were, would be, will (sg./pl), were + near\u2019heut(e) + fr\u00fch/morgen \u2018today + early/morning\u2019nah(e) + bin, war, ist, sind, seid / waren, seien, werden, wurde, wurden \u2018near + verb\u2019dem/einem + Tag(e) \u2018the/a + day, dat. ag.\u2019sehr/richtig + gern(e) \u2018very/really + gladly\u2019des/eines \u2018the/a\u2019, gen. s.g' + 162 strong monosyllabic nouns: a. masculine: Bach, Berg, Brand, Bund, Darm, Dienst, Feind, Fisch, Flug, Freund, Frost, Gang, Geist, Grund, Hang, Hof, Hund, Kampf, Kauf, Kern, Klang, Koch, Kopf, Krieg, Krug, L\u00e4rm, Leib, Lohn, Mond, Mord, M\u00fcll, Mut, Ort, Pfahl, Plan, Rang, Rat, Raub, Raum, Ring, Ruf, Rumpf, Saal, Sand, Sarg, Schein, Schirm, Schlag, Schlauch, Sieg, Sinn, Sohn, Spott, Spruch, Staat, Stab, Stahl, Stamm, Stand, Staub, Stein, Stern, Stier, Stock, Stoff, Streit, Strom, Stuhl, Sturm, Tag, Teich, Teil, Text, Tisch, Tod, Traum, Trost, Turm, Wald, Weg, Wein, Wert, Wind, Wirt, Wunsch, Zahn, Zaun, Zoll, Zorn, Zug, Zweckb. neuter: Amt, Bad, Bein, Bett, Bier, Bild, Blatt, Blech, Blut, Boot, Brett, Brot, Ding, Dorf, Fach, Feld, Fell, Fett, Fleisch, Geld, Gold, Grab, Haar, Haupt, Heer, Heft, Heil, Heim, Hirn, Hoch, Horn, Huhn, Jahr, Kalb, Kind, Kleid, Korn, Land, Laub, Leid, Licht, Lied, Lob, Loch, Mahl, Meer, Moor, Obst, Ohr, Paar, Pferd, Rad, Rind, Rohr, Schaf, Schiff, Schnitt, Schwein, Seil, Spiel, St\u00fcck, Tal, Tier, Tuch, Volk, Weib, Werk, Wohl, Wort, Zelt, Ziel(4) Phrases selected for searchDatabase for Spoken German has been compiled as a collection of spoken audio files and transcripts. While the DeReKo corpus of written German contained about 25 bn. word forms in 2014, the DGD2 corpus of spoken German contained, at the time of search, about 8.6 million word forms which were available for search in 4153 different transcripts . Thus, the size of the DeReKo corpus of written German is larger by a factor of about 3000. The search was performed over the complete set of corpora of spoken German contained in the DGD data base. It contains corpora from different speaker groups, regional origins and registers. It is well-known that different dialects of German show different behavior with respect to the presence of final schwa, and some dialects favor the presence of schwa, while others do not. The present study aims at an over-all picture, and thus includes data from the largest available range of sub-types of spoken German from different varieties, with utterances ranging from reading to storytelling.The restriction to phrases with moderately large frequencies was necessary because, as noted above, corpora of spoken language are generally much less comprehensive than those of written language. For German, the G-test) for small sample sizes, such as the number of items < 5 in one of the cells; see McDonald (dem/einem Tag(e)) had more than 5 results for all combinations. Therefore, in order to present consistent results, Fisher's exact test is applied to all cases.The DGD database was searched for the number of relevant cases as listed in (4). Then the Prosodic parallelism hypothesis was tested over contingency tables of the kind illustrated in (2), in order to test whether the number of combinations hypothesized to be preferred is higher than predicted by the given frequencies of their parts. Particular focus is placed on the strong nouns listed in (4)c, see respective section below. The test used for this purpose was Fisher's exact test of independence, with the purpose of verifying that the proportions of frequencies for one variable (presence of schwa) is dependent on the value of some other variable, or alternatively, that the frequencies are independent of each other. This test is usually recommended , indicating the level of statistical significance. Results with values for P < 0.05 are taken as confirmation for the hypothesis. A list of detailed results for all searches performed is presented in Appendix Search items and the (5) Statistical analysis; Fisher's exact testdie/der + eine/einer) form a prosodic unit not with the following noun as in der T\u00fcr(e), but with the preceding preposition, see discussion above. This would account for the non-significant result in first case given in (5). The failure for the final search item remains unexplained.Non-significant results emerge for the first and the last item used, while for a range of other constructions the hypothesis is either confirmed, or cannot be tested for lack of sufficient data j constitute a wide range of forms, with strong variation in the appearance of schwa between stems and suffix. Crucially, for present purposes, for these nouns the genitive forms all occur, in principle, with or without schwa preceding genitive ending -s, as in Amt(e)s \u2018office, gen. sg.\u2019 or Zug(e)s \u2018train, gen. sg\u2019Jahres \u2018year, gen. sg.\u2019 the schwa-containing variant is much more frequent than the competing form Jahrs, independent of contextNouns taking the suffix To illustrate, Table (6) presents the full set of relevant tokens calculated over all 162 nouns, with the number of cases found in the DGD2 database given in the cells of the table, and preferred combinations printed in bold.(6) Search results for strong nounsdes + monosyllabic and eines + bisyllabic) are higher than expected, and vice versa for the non-preferred ones. This trend is significant, with an exact P = 0.03 according to Fisher's exact test. The present study of these genitive singular forms of strong nouns thus yields a result which differs from the previous one on written German: Prosodic Parallelism is confirmed for this set of data, even without taking the role of individual lexemes into account.As inspection of (6) shows, numbers for these item combinations are too small to make calculations over individual nouns. Frequencies of combinations vary, but the forms preferred according to the Prosodic Parallelism hypothesis . Their conclusion to the reader that the respective word should be read as a bisyllabic word. In this sense, there is clearly \u201cintended prosody\u201d in the alternative spellings available. We cannot be sure that a particular reader will always follow the advice, but still the suggestion exists.While this consideration would lead to more regular prosodic phrasing for written language, the close relation between speech and prosodic features would yield the opposite result. Another reason for differences between the spoken and written modality in prosodic details may be that prosodic phrases in the spoken modality are shorter than those in the written modality. The reason is that, as mentioned above, planning processes in the spoken modality proceed under more time pressure and with fewer opportunities for revision. In consequence, more re-starts, errors, hesitations, and interruptions influence the flow of speech and thereby the structure of prosodic phrases Levelt, . In concdie or eine listed in (3). Such reduction correlates with a change in foot structure, as in the loss of a foot (defooting). Arguably, such reductions are found more often in the spoken modality than in the realization of written German. However, a written corpus does not allow for a reliable evaluation of such reductions.Finally, the reduction of function words may play a role: it has been observed by Hall and KentThe author confirms being the sole contributor of this work and approved it for publication.Funding for the study reported in this paper was provided by the LOEWE initiative of the state of Hesse, Germany (Fundierung linguistischer Basiskategorien). The sponsor was not involved in any aspect of the study and/or the article.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Scientific Reports7: Article number: 45816; 10.1038/srep45816 published online: 04062017; updated: 05162017.The original version of this Article contained an error in Affiliation 2, which was incorrectly given as:\u2018Department of Biophysics, School of Life Sciences, Manipal University, Manipal, 567014, India\u2019.The correct affiliation is listed below:\u2018Department of Biophysics, School of Life Sciences, Manipal University, Manipal 576104, India\u2019.This error has now been corrected in the HTML and PDF versions of the Article, as well as the accompanying Supplementary Information."} +{"text": "The authors would like to draw the reader's attention to errors in the following article:Cancer Sci 2017; 108: 243\u20139.Tomoki Y, Hamanaka M, Babaya A, Kimura K, Kobayashi M, Fukumoto M, Tsukamoto K, Noda M, Matsubara N, Tomita N, Sugihara K. Management strategies in Lynch syndrome and familial adenomatous polyposis: a national healthcare survey in Japan. The correct funding information is shown below:Japanese Society for Cancer of the Colon and RectumAdditionally, all occurrences of \u2018Japan Society of Colorectal Cancer Research\u2019 in the article should have changed to \u2018Japanese Society for Cancer of the Colon and Rectum\u2019.The authors apologize for these errors and any confusion these may have caused."} +{"text": "Canis lupus) is one of the most widely distributed terrestrial mammals, and its distribution and ecology in Europe and North America are largely well described. However, the distribution of grey wolf in southern China is still highly controversial. Several well-known western literatures stated that there are no grey wolves in southern China, while the presence of grey wolf across China has been indicated in A Guide to the Mammals of China, published by Princeton University Press. It is essential to solve this discrepancy since dogs may have originated from grey wolfs in southern China. Therefore, we systematically investigated Chinese literatures about wild animal surveys and identified more than 100 articles and books that included information of the distribution of grey wolves in China. We also surveyed the collections of three Chinese natural museums and found 26 grey wolf skins specimens collected across China. Moreover, we investigated the fossil records of wolf in China and identified 25 archaeological sites with wolf remains including south China. In conclusion, with the comprehensive summary of Chinese literatures, museum specimens and fossil records, we demonstrate that grey wolves does distribute across all parts of the Chinese mainland, including the most southern parts of China.The grey wolf ( Canis lupus, is one of the most widely distributed terrestrial mammals is not a subspecies of the golden jackal and should be reclassified as the African wolf, Canis lupus lupaster : Mammalia Vol. 8 Carnivora page 46-49, reported in 1987: \"the wolf, which apart from Hainan Island, the various islands in the South China Sea, and Taiwan, is spread over nearly all the country\" and \"the wolf can be seen in all provinces. Based on collected literature references and specimen samples, wolves have been identified in Muleng, Baoqing, and Genhe of Heilongjiang, in Baicheng, Kaitong, Dunhua, Jingyu, Huinan, Hunchun, Jilin, Tumenling, and Fuyu of Jilin, in Fushun and Lvda of Liaoning, in Shanhaiguan and Zhangjiakou of Hebei, in Beijing, in Hohhot and Erlian of Inner Mongolia, in Hami, Bole, Turpan, Yanqi, Korla, Aksu, Luntai, and Baicheng of Xinjiang, In Shanxi province, in Yan'an of Shaanxi, in Mianchi and Luoning of Henan, in Yichang of Hubei, in Nanjing and Qingjiang of Jiangsu, in Fujian province, in Longzhou, Ningming, and Shangsi of Guangxi, in Guangdong province, in Guizhou province, in Lushui and Chengkou of Yunnan, in Yumen, Zhangye, and Linxia of Gansu, in Menyuan, Qilian, Alaer, Golmud, and Delingha of Qinghai, in Pali, Nylamu, Tingri, Shigatse, and Naqu of Tibet, and in Shiqu, Ruoergai, Songpan, Leibo, Ebian, Kangding, Wanxian, Yibin, and Mianyang of Sichuan\" .Canis lupus desertorum Bogdanow, 1882 in Xinjiang, C. l. filchneri Matschie, 1907 in Qinghai, Gansu and Tibet, C. l. chanco Gray, 1863 in Heilongjiang, Jilin, Liaoning, Inner Mongolia (eastern part), Hebei, Beijing, Shandong, Henan and Shanxi, C. l. Nei-Mongol form in Inner Mongolia (western and mid part) and C. l. South-China form in Anhui, Jiangsu, Zhejiang, Jiangxi, Fujian, Guangdong, Hunan, Guizhou, Yunnan, Hubei and Sichuan Furthermore, Wang (200) described the subspecies/subtypes of wolf in China and reported that the wolf was distributed across all parts of continental China. Chinese wolves were divided into five subspecies and forms: In order to obtain an updated and comprehensive description of the distribution of wolves in China, we investigated more than 100 articles containing information about the pressence of wolf at a regional level , and depletion of prey . Also inThe data about wolf distributions that we here present were investigations on either provincial or local level, whereas, a comprehensive ecological survey of the wolves in China. It is therefore not clear how the wolf populations in the different parts of China are interrelated. For example, it is not clear whether wolves recorded in the southern provinces represent permanent populations, or a steady stream of individuals migrating from the northern provinces. However, it is notable that wolves have been recorded across virtually the entire continental China, including southern Chinese province Yunnan as late as in 2011 and provinces Guangdong and Guangzhou in 2000. These findings indicate a consistent presence of permanent populations across southern China. Moreover, to obtain a comprehensive picture of the status of the wolves in China, it is necessary to carry out both ecological and genetic studies, e.g., in concerning the genetic relationships either among the wolf populations across China and between these and worldwide wolf populations.This study points out misconceptions in the western literature about the distributions of wolves in China. The origin of this problem is not clear, but it can be traced back as far as an article in 1985 from which the factoid has, stepwise, been passed on to other articles . It is pWith a comprehensive summary of Chinese literature, specimens and fossil records, we showed that wolves are present across all parts of the Chinese mainland, including the southern parts of China. Hereby we corrected an error in western literature, in which most sources stated that wolves are not present in the southern China, and some even claimed that wolves have never been presented there, even in ancient times. There is no comprehensive description of the current distributions of wolves across China, and therefore this study serves both to give an updated description of wolf distributions in China, and to make this significant information available to an international audience."} +{"text": "The MAHC is a guidance document that jurisdictions can use to update or implement codes, rules, regulations, guidance, laws, or standards governing swimming pools, spas, hot tubs, and other public, treated, recreational water venues to reduce infectious disease outbreaks, drowning, and chemical injuries.The first edition of the Model Aquatic Health Code (MAHC) was released on August 29, 2014, and is now available from CDC online at In the United States, no federal agency regulates the design, construction, operation, and maintenance of public swimming pools and other public, treated, recreational water venues. All pool codes are independently written and enforced by state and/or local agencies. In 2005, local, state, and federal public health officials and representatives of the aquatic sector requested that CDC develop a model, evidence-based code. Since 2007, CDC has led a national collaborative effort with public health, industry, and academic representatives from across the United States to develop the MAHC.http://www.cmahc.org) is a nonprofit organization created in 2013 to support and improve public health by promoting healthy and safe aquatic experiences for everyone. CMAHC members will suggest MAHC revisions for CDC\u2019s final determination.CDC will work with national partners to periodically update the MAHC to ensure it stays current with the latest industry advances and public health findings. The Conference for the Model Aquatic Health Code (CMAHC) ("} +{"text": "Pharmaceuticals improved its ranking [Pharmaceuticals confirms its position in the first quartile in the category of pharmaceutical science. Moreover, papers published in our journal in 2013 and 2014 have been cited 4.5 times, on average, in 2015.As explained in the editorial written 12 months ago [It is my pleasure to confirm the progress recorded in 2016. Indeed, the number of published manuscripts has jumped from 45 to 79 in 2016 volume. This includes submissions received in 10 completed Special Issues. They were dedicated to the First International Electronic Conference on Medicinal Chemistry , Thierry Besson , Francois Dufrasne , Marc Le Borgne , Andrea Porcheddu , Osvaldo A. Santos-Filho , Gary J. Stephens , and Nigel Yarlett .Pharmaceuticals confirmed its status as an international journal by being present as a media partner, an exhibitor, or a sponsor at national and international meetings among which were:Biosensors 2016, Twenty-sixth Anniversary World Congress on Biosensors, 25\u201327 May, Gothenburg, Sweden;Thirtieth France-Belgium Meeting of Pharmacochemistry, 25\u201327 May, Amboise, France;Aptamers in Bordeaux 2016, 24\u201325 June, France;CLINAM 9/2016 Conference and Exhibition, European and Global Summit for Cutting-Edge Medicine: Clinical Nanomedicine and Targeted Medicine, Enabling Technologies for Personalized Medicine, 26\u201329 June, Basel, Switzerland;ACS National Meeting and Exhibition, 21\u201323 August, Philadelphia, PA, USA;R\u00e9union du Groupement des Pharmacochimistes de l\u2019Arc Atlantique, 25\u201326 August, Angers, France;Eighth International Conference on Protein Kinase CK2, 6\u20139 September, Homburg, Germany;Thirteenth European Biological Inorganic Chemistry (EuroBIC 13) Conference, 28 August\u20131 September, Budapest, Hungary;Twenty-fourth National Meeting in Medicinal Chemistry, 11\u201314 September, Perugia, Italy.Fourth Conference on Innovation in Drug Delivery: Site-Specific Drug Delivery, 25\u201328 September, Antibes-Juan-les-Pins, France;Pharmaceuticals was the organizer of the Second International Electronic Conference on Medicinal Chemistry [hemistry . The evehemistry , submittPharmaceuticals Travel Award for Young Investigators [Mentions should be made, in addition, that we received 83 outstanding applications for the 2016 Pharmaceuticals will offer a travel grant to help support a young investigator in her/his professional career. Details of the competition can be found on our website [http://sciforum.net/conference/ecmc-3.In 2017, we shall pursue our efforts to raise the journal to a better position still and to increase its visibility. Therefore, we can already announce that It is my pleasure to end this editorial by wishing you a healthy and prosperous new year. This is also the opportunity for me to warmly thank, for their confidence, our authors, readers, and reviewers, as well as the scientists of the editorial board, members of our teams in Basel, Barcelona, Beijing, and Wuhan, and our sponsors."} +{"text": "In this paper, we study the derangement polynomials and investigate some interesting properties which are related to derangement numbers. Also, we study two generalizations of derangement polynomials, namely higher-order and r-derangement polynomials, and show some relations between them. In addition, we express several special polynomials in terms of the higher-order derangement polynomials by using umbral calculus.The problem of counting derangements was initiated by Pierre R\u00e9mond de Montmort in 1708 (see Carlitz in Fibonacci Q. 16(3):255\u2013258, The. The\\docFor x)\u2208P, by , we getFrom , we noteFrom , we easiLet For The Bernoulli polynomials are given byWe know that the Euler polynomials are defined byThe falling factorial sequence is defined asThe Stirling numbers of the first kind are defined byThe Stirling numbers of the second kind are also given by the exponential generating function 1It is well known that the Bell polynomials are defined by the generating functionFrom , we haven element set (see [A derangement is a permutation that has no fixed points. The derangement number mentclass2pt{minimset (see ). The prmentclass2pt{minimset (see ). The fiIndeed, From , we noteBy using , it is nr , from we haveThus, by , we getIn , we takeNow, we observe thatFrom , we noteBy and 2.1, we getFrom , we can Forwe haveFrom , we haveIn particular,Comparing the coefficients on both sides of , we haveTherefore, we obtain the following corollary.Forwe haveandr byr.For r-derangement numbers, denoted by r-elements are in disjoint cycles. It is known that the generating function of the r-derangement numbers is given byFor r-derangement polynomials given byr-derangement numbers. By . From and (2.20). From , we haveTherefore, by and 2.3, we obtaForwe haveNow, we observe thatOn the other hand, by , we getFrom and 2.3, we haveIn particular, for Therefore, by and 2.3, we obtaForwe haveMoreover,By , we easiComparing the coefficients on both sides of , we haveFrom , we can Thus, by , we getFor \u22122, from and . From , we haveTherefore, by and 2.4, we obtaForwe havewhereLet us take Hence, by and 2.4, we getAssume that Then, by , we getThus, from , we noteForwe havewhereFor Thus, we note thatFor HenceFor Thus, we getFor HenceThe ordered Bell polynomials are defined by the generating functionrs. From and , by and , by , we getTherefore, we obtain the following theorem.Forwe haveFor Therefore, by and 2.5, we obtaForwe haver-derangement polynomials, and showed some relations between them and also with some other special polynomials. In addition, by using umbral calculus, we derived a formula expressing any polynomials as linear combinations of higher-order derangement polynomials and illustrated this with several special polynomials.In this paper, as a natural companion to derangement numbers, we have investigated derangement polynomials and derived several interesting properties on them which are related to derangement numbers. Also, we have considered two generalizations of derangement polynomials, namely the higher-order and The introduction of derangement numbers goes back to as early as 1708 when Pierre R\u00e9mond de Montmort considered some counting problem on derangements. However, it seems that the umbral calculus approach to the derangement polynomials and their generalizations has not yet been done. In this paper, we have used umbral calculus in order to study some interesting properties on them, certain relations between them, and some connections with several other special polynomials."} +{"text": "As usually verified in many malignancies, the majority of the scientific information about renal cell carcinoma (RCC) is produced in developed countries mainly in North America and Europe. This knowledge is derived from great casuistries, joined in multi-institutional collaborative study groups or in International diseases consortiums.Consistent epidemiologic and scientific data originated in the Latin America (LA) are lacking. LA is a large subcontinent, composed by more than 20 countries (much of them great economies), encompassing around 640 million habitants. Latin American population ethnicity is unique, due to an intense miscegenation, differing from northern hemispheric populations. The LA\u2019s population was composed by several civilizations over the years: pre Colombians, (Amerindians), black slaves descendant\u2019s (distinct groups of the African slaves that were sent to North America and Caribe). The predominance of Europeans in LA corresponded to Iberians, and Italians, few French and Germans. We have few Anglo-Saxon, Scandinavian and Northern and Eastern Europeans. Regarding Middle East and Africans, the more prevalent immigrants were Syrian, Lebaneses, Jewishs and few Armenians. Also, there are few Arabic, Persian and North African populations. From Asia, the predominance has been established by Japanese and in the last decades, by some Korean and Chinese. There is almost no people from South Asia, Oceania and Pacific Islands etc., differing from US, for example. The LA racial miscegenation resulted in particular genetic groups such as Mulattoes, Mestizos, Zambos, Cimarron\u2019s, Cafuzzos, mamelucos etc , 2. In tHowever, the socioeconomic level and the human development index among LA\u2019s populations in general are under than desired. Health care systems in our subcontinent are heterogeneous, being possible to find in a same country (or in a same city), side by side, the more developed, and the more precarious medical services. Additionally, the Latin American Institutions, and its practitioners are not skilled in participating in multicenter collaborative study groups. The language may constitute an additional barrier, since the number of non-native English speakers (and writers) is large. At the same time, the background and the funds available to incentivize scientific productions are insufficient, in contrast with several primary and more urgent health requirements in LA.th American Urological Society Annual Meeting in San Diego, colleagues from Brazil (SCZ) and Uruguay (DAC), decided to create an international, multicenter, nonprofit, collaborative study group, focused on kidney cancer, named LARCG .In face of this scenario, in May 2013, during the 108The main generic role of LARCG is to promote knowledge and the research development regarding renal cell carcinoma (RCC) in LA. In order to reach this, it has become necessary to aggregate people and Institutions dedicated to this disease.Among the scopes of LARCG, the main ones were: 1) the creation of a great and multifaceted data bank with information of RCC in LA; 2) to stablish international scientific cooperation between the LARCG institutions and developed research centers or with collaborative uro-oncological intergroups; 3) to proportionate facilities that result in the production of high level scientific publications; 4) To stimulate the participation of LARCG members in worldwide recognized scientific meetings.The first step to concretize our aims was to invite LA\u2019s key opinion leaders, to participate, and we had a quick and massive adhesion . On 2014, after a few months we had the adhesion of 24 institutions from six countries , constituting the first round of the LARCG.At the same time, through electronic assemblies, a statute was approved by all LARCG members. According to this agreement, it was created the Executive Directory, the Member\u2019s Council, and the Scientific and the Ethics Committees. In each participating center, an Urologist Leader (UL) was nominated.The UL must diffuse the LARCG ideas on each center recruiting urologists, and designating expert uro-pathologists, and clinical oncologists. These colleagues constitute the LARCG Pathol Branch and the LARCG Oncol Branch respectively, reinforcing the multidisciplinary characteristics of the group.Today, LARCG is active, supported by annual fees paid by its members and is consolidated: www.larcg.org .First epidemiological survey and an early survival analysis\u201d, form LARCG. These results were presented for the first time at the Main Session of the CAU - Confederacion Americana de Urologia Meeting, in Punta del Este Uruguay, in November, 2014. During this congress, it was realized the First Annual LARCG Meeting, with the presence of the majority of our members. Few months later, in 2015 April, these first analyses results, and the structural aspects of the LARCG, were presented at the \u201c2015 Spring SWOG (Southwest Oncology Group) Meeting\u201d, in San Francisco, California. . After a few weeks, LARCG performed it\u2019s Second Annual Meeting during the 2015 AUA Annual Meeting in New Orleans LO, in a meeting room supported by the AUA .The first step in the scientific direction was the creation of an extensive data bank, containing 176 demographical, clinical, laboratorial and pathological variables, all of them previously codified and with careful protection of the patients\u2019 identifications. This data bank was sent to 24 institutions participants of the first round of the LARCG, in January 2014, and there were six months for the return of the information. At the end of 2014, we received information from 4280 RCC Patients. From these group, 3817 patients were eligible for a realization of the \u201cLARCG promoted Scientific International Meetings in S\u00e3o Paulo, in March 2015, at AC Camargo Cancer Center, and in October, 2015, in the British Hospital in Buenos Aires.Third LARCG Annual Meeting, realized in San Diego, during the 2016 AUA Meeting, under the support of the AUA. In this Section, we were proud to receive a special honored Guest, W. Marston Linehan, MD.In the end of 2015, the first LARCG season of submission of scientific projects was opened, and we received several applications, fourteen of them were approved by the Ethics and the Scientific Committees. All of these projects were presented during the During the 2016 Meeting of the Associacion Argentina de Urologia, in Tucuman-Argentina), \u201cContemporary outcomes in the Management of Metastatic Renal Cell Carcinoma from the Latin American Renal Cancer Group (LARCG)\u201d was presented . In OctoThe second Round: In 2015 LARCG finalized the adhesion of 45 centers, from Brazil, Uruguay, Argentina, Chile, Peru, Bolivia, Mexico and Spain. At this time, our Scientific Committee corrected and enhanced our data bank, and sent it to all centers, that had some months to fill it and/or to correct the previous imprecisions and return it to us. At the end of 2016, we finalized the second round, having information of 5223 patients . The information is customized in a data bank. Now the specific variables\u2019s informations has been sent to the LARCG investigators which had aprooved research projetcs.One of the most significant initiatives of the LARCG is to integrate the demographic, clinical data with pathological samples of each respective patient. For this task, we must acknowledge the non-interested collaboration of Dra. Isabela Werneck da Cunha, MD, PhD, (Leader of the LARCG Pathol), the LARCG Pathologists, and the personal contribution of Dr. George Netto, MD. Those skilled pathologists are centrally reviewing and reclassifying thousands of samples, according to the 2012, ISUP - International Society of Urological Pathology Consensus . From eaThere is a signed international agreement between two LARCG Centers and Lee Moffitt Cancer Center, from Tampa, US, through Dr. Philippe P. Spiess, MD and Jorge Lockhart, MD.Other collaborations has been stablishing with one of the SWOG\u2019s centers and AC Camargo Cancer Center. Some LARCG centers will collaborate with the recently aproveed project INCITO-INOTE 8, leadeared by VIlma Regina Martins, MSc, PhD.For 2017, LARCG web site, originally in Spanish, will become bilingual, including the English idiom. Periodically, at our home page, newsletters, editorials, clinical cases discussions will be available.LARCG Annual Meeting (4th) will be held in Boston 2017, during the next AUA Annual Meeting. During this meeting, the research projects underway will be presented, and worldwide recognized RCC Speakers will be invited.The Next Negotiations are in course to establish future collaborations with international research groups and with RCC patient\u2019s protection and educational groups. We are now looking for a sponsor institution, that can support LARCG in its several and infrastructural logistics requirements.We wish a bright 2017 for all LARCG members, collaborators and of course, for our patients.Editor Associado, International Braz J UrolDivis\u00e3o de Urologia do A.C. Camargo Cancer CenterFunda\u00e7\u00e3o A. Prudente, S\u00e3o Paulo, BrasilSt\u00eanio de C\u00e1ssio Zequi, MD, MSc, PhD"} +{"text": "Chris S Earl, Teh Wooi Keong, Shi\u2010qi An, Sarah Murdoch, Yvonne McCarthy, Junkal Garmendia, Joseph Ward, J Maxwell Dow, Liang Yang, George A O'Toole & Robert P RyanEMBO Molecular Medicine, has been retracted by agreement between the authors of the study, CSE, TWK, SQA, SM, YMcC, JG, JW, JMD, LY, RPR, the journal Chief Editor and the EMBO Head of Scientific Publications in accordance with the outcomes of independent investigations conducted by the University of Dundee and University College Cork.The above article, published May 20 2015 in GAO'T disagrees with the text of this retraction notice, albeit not with the retraction.The following issues are noted:PLoS One 8(12): e82432 , although in a number of cases the patient's gender is at odds between the two reports.Table\u00a01 contains clinical data described in the paper as being derived from a cohort of asthma patients. However, the provenance of this data is unclear. Based on the evidence available, the University of Dundee investigation concluded that the majority of the patient cohort is likely to be a subset of a cohort of cystic fibrosis patients reported in The RNAseq data are unavailable on the European Nucleotide Archive under the reported accession number ERG003569. RNAseq data were uploaded with accession number ERS654066 before publication.The paper describes use of both prednisolone and prednisone, yet only the latter was used in the study."} +{"text": "Scientific Reports 10.1038/s41598-017-01335-w, published online 26 April 2017Correction to: In the original version of this Article, Teigang Liu was incorrectly listed as being affiliated with \u201cKey Laboratory of Chinese Internal Medicine of Education, DongZhiMen Hospital, Beijing 100070, China\u201d.The correct affiliation is listed below:College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.This has now been corrected in the HTML and PDF versions of this Article."} +{"text": "In the paper the presCSIR Emeritus Scientist, Department of Zoology, Lucknow University, University Road, Lucknow 226007, India.Acknowledgements\u2019 section:The following information is added in the \u2018\u201cThanks are due to CSIR, New Delhi, for award of Emeritus Scientist Project to PKM. Thanks are also due to Vice Chancellor, Lucknow University, Lucknow, for providing laboratory space and computational facilities to PKM for carrying out part of the study, data analysis and manuscript preparation.\u201d"} +{"text": "Throughout September, approximately 3,000 organizations will participate in activities in support of National Preparedness Month. CDC supports this initiative by partnering with national, regional, state, and local government agencies, as well as private and public organizations, to encourage persons to take part in preparedness efforts at home, school, and throughout their communities.For Preparedness Month 2014, CDC\u2019s Office of Public Health Preparedness and Response has focused its efforts on developing messages and products designed to meet the needs of vulnerable populations , CDC is http://www.cdc.gov/phpr.The unpredictable nature of disasters makes personal preparedness a necessity. In the case of vulnerable populations, there are unique considerations that must be taken into account when preparing for emergencies ,5. Addit"} +{"text": "Incorrect Affiliation4Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China, 5School of Medicine, Jiangnan University, Wuxi, China\u201d, it should be \u201c4School of Medicine, Jiangnan University, Wuxi, China\u201d. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the published article, there was an error in affiliation . Instead of \u201cThe original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The correct name is: Mirza Faisal Qaseem. The last author\u2019s name is incorrect. The correct name is: Arshad Mahmood Khan. The correct citation is: Amjad MS, Qaseem MF, Ahmad I, Khan SU, Chaudhari SK, Zahid Malik N, et al. (2017) Descriptive study of plant resources in the context of the ethnomedicinal relevance of indigenous flora: A case study from Toli Peer National Park, Azad Jammu and Kashmir, Pakistan. PLoS ONE 12(2): e0171896. In the author contributions, Muhammad Shoaib Amjad (MSA) should be listed as one of the persons who contributed to Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Visualization and Writing\u2013review & editing.There is an error in the last sentence under the subheading \u201cCollection and identification of plants\u201d in the Materials and methods section. The correct sentence is: The fully determined vouchers were deposited in the herbarium of the Department of Botany, Women University of Azad Jammu & Kashmir, Bagh, Pakistan."} +{"text": "The authors of the above paper retract this article due to concerns about the integrity of the data and the validity of the conclusions. The first author, Brandi M. Baughman, has admitted to the co-authors and the Office of Research Integrity at NIH that she falsified and/or fabricated data and text concerning Figs 2, 3, 4, 5, 6, 8, S1, S2, S3, S4, and S5, for which she takes sole responsibility.Subsequent to the paper being published, further experiments by co-authors Wang, Stashko, and Pearce have verified that a major conclusion of this article is invalid: UNC10112646, UNC10225354, and UNC10225498 are not inhibitors of PPIP5K, contrary to the claims in the published paper.In light of these concerns, all of the authors have agreed to retract this article."} +{"text": "Professor Er-Mi Zhao, Herpetologist, 1930-2016Academician Er-Mi Zhao, Professor of the Chengdu Institute of Biology, Chinese Academy of Sciences, and Sichuan University, passed away on 24 December, 2016, to the great loss of both Chinese and world herpetology. As one of the most internationally renowned Chinese herpetologists, Academician Zhao represented a remarkable era of Chinese herpetology and made a significant contribution to global research, both academically and spiritually. He played a significant role in our understanding of the amphibians and reptiles of Tibet, herpetofauna of the Hengduan Mountains, taxonomy of Chinese snakes, and biogeography of the East Asian islands. His distinguished studies laid a solid and substantial foundation for research by future generations of young herpetologists, and had an extensive and profound impact on the development of the field.Agkistrodon expert, wrote to Academician Zhao in 1989. In 1993, Herpetology of China (Liua (Liua shihi) , Dinodon rosozonatum , Achalinus hainanus , Trimeresurus medoensis , Ovophis monticola zayuensis , Plagiopholis unipostocularis (Viridovipera medoensis) , and Mt. Mang pit viper (Protobothrops mangshanensis) and Liuaa shihi) , and 41 wanensis , Achaliniguensis , Natrix x optata . Ranodonnpaensis , Megophrangensis , Hyla tsingensis , Rana kugwuensis , Microhy mixtura , Leioloingensis , Xenopelocularis , Opisthogxiensis , Agkistrdaoensis , Trimereengensis , Phrynocuanensis , Oligodoizonatum , Macropirontalis , Scincelrenensis , Scutigeuginosus , Rhabdoplabialis , Platymaiculatus , Stauroihanensis , Calotesdogensis , Tenuidadogensis , Rana tegerensis , Eumecesces liui , Trimerehanensis , Cuora zra zhoui , Amphies metusia , Oreolalunctatus , Rana rortingeri , Rhabdops adleri , Laudakiakia wui , Laudakipenfussi , Rana zha zhengi , Opisthois cheni , Rhacophhainanus , and Gloijianlii , as wellaoensis) , Medog ganensis) . He alsoanensis) and expaanensis) .Academician Zhao brought new insight and perspective on the geographical division of amphibians and reptiles in China, the amphibian and reptile fauna in the Hengduan Mountain area, the classification of snakes distributed in China, and the zoological geography of the East Asian Islands. He zoned the southern slopes of the Himalayas as a new sub-southwest region of the Indo-Chinese sub-region in the oriental realm according to the actual distribution of species in Tibet, and first proposed a new \"South of the Himalayan Sub-region\" based on the distribution of reptiles . In addiProfessor Zhao also did outstanding work in scientific practice. He developed measures for the prevention and management of venomous snakes in the grasslands in western Xinjiang, and advanced the concept of medical geography of venomous snake bites in China and YunnZoological Research from 1997 to 2014, he fulfilled his duty faithfully and diligently, and provided vital and constructive promotion of the journal. Zoological Research is extremely grateful for his exceptional contribution and dedication, and it is with deep regret and sorrow we note his passing. His deep passion, persistence, optimism, and strict scientific attitude in chasing the truth showed his invaluable spiritual wealth, and is an inspiration to every one of us.Academician Zhao was not only a devoted scholar, but also played active roles in helping young researchers and in disseminating scientific knowledge. He served on the Executive Committee of the International Amphibian and Reptilian Society in 1983, and as the Chairman of Chinese Herpetologists in the IUCN (1991-2001). During his tenure as an academic advisor on the Editorial Board of Editor's note: The facts and material stated here in regards to Academician Zhao's academic achievements were provided by his students, Dr. Jia-Tang Li , Dr. Jing Che , Dr. Song Huang , Peng Guo and Dr. Yue-Zhao Wang . This essay was compiled by Zoological Research."} +{"text": "People aged 65 and above have consistently been omitted from research on the epidemiology of psychotic disorders. Correspondingly, little is known about the incidence of very late-onset schizophrenia-like psychosis (VLOSLP). We aimed to characterise the incidence of VLOSLP in a Swedish population cohort, including how incidence varied by age, sex, migration, deprivation, traumatic life events, and social isolation.We conducted a Swedish population-based cohort study to examine the incidence of VLOSLP by potential environmental risk factors. The cohort, born in 1920\u20131949 and living in Sweden, were followed up from age 60 until the end of follow-up (30th December 2011), emigration, death, or diagnosis with a non-affective psychotic disorder. We used Cox regression to obtain hazard ratios and 95% confidence intervals for VLOSLP by age, sex, migration, disposable income at age 60, and the experience of the death of a partner or child, adjusting for potential confounders.In a cohort of 2,955,796 people, we identified 14,825 cases with VLOSLP, with an overall incidence rate of 38.1 (95% CI: 37.5 \u2013 38.7) per 100,000 person-years at-risk. Rates were higher amongst migrants from North America , Europe , Russian-Baltic regions and Africa compared to Swedish-born, with a lower rate in migrants from the Middle East . Rates were higher in those with the lowest income , who experienced the death of a partner , death of a child in infancy , and those without a partner or children .In this large, national cohort study we identified several potential risk factors for developing psychosis later in life, including migration, deprivation, social isolation and traumatic life events. This may have important implications for our understanding of the aetiology of VLOSLP and could help to inform public mental health and service planning."} +{"text": "This study examines how the relationship between urbanization and the carbon intensity of well-being (CIWB) (measured as a ratio of carbon dioxide emissions and life expectancy) in most nations from 1960\u20132013 varies based on the economic context and whereabouts of a substantial portion of a nation\u2019s urban population. To accomplish this, we use the United Nations\u2019 (UN) definition of slum households to identify developing countries that have substantial slum populations, and estimate a Prais-Winsten regression model with panel-corrected standard errors (PCSE), allowing for disturbances that are heteroskedastic and contemporaneously correlated across panels. Our findings indicate that the rate of increase in CIWB for countries without substantial slum populations begins to slow down at higher levels of urbanization, however, the association between urbanization and CIWB is much smaller in countries with substantial slum populations. Overall, while urbanization is associated with increases in CIWB, the relationship between urban development and CIWB is vastly different in developed nations without slums than in under-developed nations with slums. An esse2 emissions. In these studies, urbanization is often observed as form of socioeconomic development. Liddle argues that macro-level quantitative research assessing the relationship between urbanization and CO2 emissions \u201ccomes in two different flavors\u201d and can be distinguished between studies that assume the relationship between urbanization and CO2 is one-way causal, and studies that assume the relationship is multi-causal [2 emissions. However, these studies are mostly limited to exploring the relationship between urbanization and CO2 emissions in specific nations . These 2 emissions, and assess the specific relationship between increases in the percentage of urban populations and changes in CIWB. As mentioned previously, some studies have found that urbanization can have an attenuating relationship with carbon dioxide emissions [one or more of the following conditions: access to improved water; access to improved sanitation; sufficient-living area; durability of housing; and security of tenure\u201d. However, in practice the first four of these indicators are typically used in defining a slum household because secure tenure data are generally unavailable. We create an interaction term interacting percent urban population with a dummy variable that identifies countries with substantial urban slum populations and used it as a variable. The logic behind this interaction term is to capture the different association that urban development in developing regions with substantial slum populations might have with both life expectancy and carbon dioxide emissions.The logic of our modeling approach is to control for known drivers of life expectancy at birth and COmissions , 28. Spemissions and CIWB, and control for theoretically relevant correlates of CIWB , finding that the percent of individuals living in urban areas has a positive and statistically significant relationship to nations\u2019 CIWB through time. To build on model 1, in model 2 we assess whether the relationship between urbanization and CIWB is non-linear and create a quadratic term for percent urban populations, finding that it is not. In model 3, we create a dummy variable that uniquely identifies developing nations with slums populations and interact this variable with percent of individuals living in urban areas. The coefficient for this variable specifically displays the relationship of a proportional increase in the percentage of individuals living in urban areas within developing nations that have slums populations. Additionally, the coefficient for percent urban population in model 3 shows the association that developed countries that do not have substantial slum populations have on CIWB. The findings in model 3 indicate that for developing nations with slum populations the association between urbanization and CIWB is substantially lower than it is in all other nations included in our model.In model 4, we find that the quadratic term for the variable representing the percent of individuals living in urban areas and its quadratic term are significant at a .05 test. Additionally, we find that the variable for interaction effect of percent of individuals living in urban populations and developing nations with slums populations are each significant at a .05 test. This suggests that (1) the relationship between percent urban population and CIWB is significantly different in developing countries that have slum populations than all other nations, and (2) that the relationship between percent urban population and CIWB in both developing nations that have slum populations and all other nations is non-linear. However, because the quadratic terms for both percent urban population and the interaction effect of developing nations with slum populations are significant, it is easiest to interpret their relationship to CIWB graphically. As can be seen in 2 emissions, such as energy consumption and the manufacturing of impervious surface area, than it does in nations with no slums. However, this also suggest that urban growth has a smaller positive association with life expectancy at birth in nations with substantial slum populations than in nations with no slums.Here we find that the rate of increase in CIWB for countries without substantial slum populations begins to slow down at higher levels of urbanization and the association between urbanization and CIWB is much smaller in countries with substantial slum populations. One potential explanation for the findings presented here is that, in developing nations with substantial slum populations, urban growth has a smaller association to processes that produce COPrevious research has also suggested that greater levels of urban density are associated with declines in counterfactual energy use , which oThough it can be assumed that because we created an interaction term that specifically distinguishes between countries with slums and countries that are developed and/or have no slums that the differences observed in this analysis are a result of slums, we caution against such an interpretation. It would be inappropriate to argue that this is the only difference between urban development in countries that have slum populations and those that do not. One benefit to observing the association of rises in all urban populations, and not just substantial slum populations, however, is that it does allow our model to capture some of the other differences that exist between urban development across these groups.We believe that the most notable contribution of this study is its ability to help further our understanding of the nuanced relationship between urban growth, well-being, and carbon dioxide emissions. Similar to previous studies in this area, we demonstrate the complexity of urban development by finding that there is not a linear relationship between CIWB and urban population growth in developing countries that have slum populations, and in countries that do not fit this specific criterion. The present study also shows the need for future research and policies aimed at reducing carbon emissions, while simultaneously increasing human well-being, to be mindful of the contrast between urbanization in developing nations that have slums and other countries. As mentioned above, in this study we are unable to directly examine the relationship between slum-patterned urban development and CIWB, or to compare this relationship directly with non-slum-patterned urban development\u2019s relationship to CIWB, and we caution against such an interpretation. Here, our focus has been on the differences in the association between CIWB and urban development patterns in developing nations with substantial slum populations relative to nations without substantial slum populations as a whole, and not, per se, on the differences between slums and non-slum urban areas. However, we encourage future research to address the issue of slum development patterns and sustainability more directly. Finally, we note that, based on the observed trajectory of nations with and without slum populations, urbanization alone does not appear as though it is effective at reducing growth in CIWB. According to our findings, even as countries reach 100 percent urbanization the attenuation of CIWB is still fairly small (this is even more the case for nations with slum populations). If the current trajectory of urban growth continues, deepening our understanding how urbanization influences well-being and environmental sustainability will be increasingly crucial. The findings presented here offer a glimpse into how researchers can observe these relationships in a way that captures some of the differences in the forms of urbanization that can be seen across the globe.We constructed a Prais-Winsten regression model with panel-corrected standard errors (PCSE), allowing for disturbances that are heteroskedastic and contemporaneously correlated across panels . We emplWe use nations as our unit of analysis, and include year and country specific intercepts to control for potential heterogeneity that is temporally invariant within nations, and cross-sectionally invariant in time periods. Additionally, we correct for AR (1) disturbances within panels, treating the AR(1) process as common to all panels because there is no theoretical reason to assume the process is panel specific . Our couTo construct our dependent variable, we employ World Bank, World Development Indicators , data onAs in previous research concerning well-being and environmental intensity , 33, 46,We include GDP per capita, measured in constant 2005 US dollars, as an independent variable in order to account for the level of economic development within nations. Previous research has found economic development to be a critical factor in country-level CIWB outcomes , 20. SpeFollowing York and Colleagues , we log it\u201d, our outcome of interest, represents the carbon intensity of well-being for nation i in year t; \u201cPercent Urbanit\u201d indicates the percent of the population the is urbanized in country i during year t; \"Dummy Variable for Nation with Slumsit\u201d indicates whether nation i has slum patterned urbanization in year t; \"Populationit\" is a control for total population size of nation i in time t; \u201cGDP per capitait\" represents nation i\u2019s GDP per capita in year t, \u201cPercent Population 15-65it\u201d indicates the percent of the productive population during time t in country i; \u201cPercent Population Over 65it\u201d represents the percent of the population that is typically unproductive in country t during year t; \u201cyeart\u201d is a control for period specific effects; ui is a control for nation specific, non-contemporaneous, effects; and eit is the residual term for nation i in period t.The form of the Prais-Winsten regression model with panel corrected standard errors including all independent variables used in Angola, Argentina, Bangladesh, Belize, Benin, Bolivia, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, Chile, China, Colombia, Comoros, Democratic Republic of The Congo, Republic of The Congo, Costa Rica, Cote d\u2019Ivoire, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Ethiopia, Gabon, Ghana, Grenada, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iraq, Jordan, Kenya, Lao, Lebanon, Lesotho, Madagascar, Malawi, Mali, Mexico, Mongolia, Morocco, Mozambique, Namibia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Panama, Paraguay, Peru, Philippines, Rwanda, Saudi Arabia, Senegal, Sierra Leone, South Africa, Sudan, Suriname, Tanzania, Thailand, Togo, Trinidad and Tobago, Turkey, Uganda, Vietnam, Zambia, Zimbabwe.Afghanistan, Albania, Algeria, Antigua and Barbuda, Armenia, Aruba, Australia, Austria, Azerbaijan, The Bahamas, Bahrain, Barbados, Belarus, Belgium, Bhutan, Bosnia and Herzegovina, Botswana, Brunei Darussalam, Bulgaria, Cabo Verde, Canada, Croatia, Cuba, Cyprus, Czech Republic, Denmark, Djibouti, Eritrea, Estonia, Fiji, Finland, France, Gambia, Georgia, Germany, Greece, Hong Kong, Hungary, Iceland, Iran, Ireland, Israel, Italy, Japan, Kazakhstan, Kiribati, Republic of Korea, Kuwait, Kyrgyz Republic, Latvia, Liberia, Libya, Lithuania, Luxembourg, Macao, Macedonia, Malaysia, Malta, Mauritania, Mauritius, Micronesia, Moldova, Montenegro, Netherlands, New Zealand, Norway, Oman, Papua New Guinea, Poland, Portugal, Qatar, Romania, Russian Federation, Samoa, Sao Tome and Principe, Serbia, Seychelles, Singapore, Slovak Republic, Slovenia, Solomon Islands, Spain, Sri Lanka, St. Lucia, St Vincent and The Grenadines, Swaziland, Sweden, Switzerland, Syria, Tajikistan, Timor-Leste, Tonga, Tunisia, Turkmenistan, Ukraine, United Arab Emirates, United Kingdom, United States, Uruguay, Uzbekistan, Vanuatu, Venezuela, West Bank and Gaza, Yemen.S1 FileThis file contains all data used to perform the analyses presented by the authors above.(CSV)Click here for additional data file."} +{"text": "One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the \u201cNetwork for Evaluation of One Health,\u201d an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes , which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy. One Health (OH) positions health professionals as agents for change and provides a platform to both measure and manage determinants of health seldom fully covered by medicine or public health alone. The integration of human, animal, and environmental health has a long history \u20134. RecenThe purpose of this paper is to identify and describe evaluable characteristics of OH approaches, and to present what they can encompass and achieve. This provides a basis for evaluation of OH initiatives and their outcomes, which could not be achieved using standard, sectoral approaches.The characteristics of OH presented here resulted from a NEOH workshop held in June 2015. Twenty-five experts from 14 countries representing public, human, veterinary, wildlife and environmental health, food safety, agriculture, agro-economics, geography and development aid, research, government, and international organizations attended. The notion evolved that there are specific conditions that demand integrated approaches, which we named drivers. At the other end, specific outcomes are expected to be produced as a result of these integrated OH approaches. The principal OH approach as such was considered to consist of a specific operational paradigm requiring a supporting infrastructure to become effective. Figure Factors identified as drivers Figure define tAlthough OH initiatives can range from development projects to educational programs, research projects, and intergovernmental strategies, they often have specific operating principles, characterized by a way of thinking, planning, and working. We selected this classification, as it represents a sequence from abstract thoughts over planning of an initiative to concrete implementation. The realization that certain health and welfare challenges cannot be dealt with from a single disciplinary perspective thus calls for a re-evaluation of approaches to deal with health and welfare challenges. \u201cOH thinking\u201d is holistic, inclusive, respectful, and tolerant, as opposed to approaches that are specific, reductionist, with a tendency to focus on single or limited outcomes that impact positively on few people only. It considers multiple scales of life, disciplines, sectors, species, paradigms, and demographics, and integrates at different spatial scales . This should reflect the connected nature of social relations and social systems, both in their material and symbolic dimensions as well as the degradation of national resources due to globalization . \u201cOH plaConsequently, \u201cOH working\u201d relies on transdisciplinary collaboration that embraces contributions from the biological, natural and social sciences, and actively includes stakeholders in the process, from problem definitions to resolution. To operate as conceived, OH must rely on adequate information infrastructure and foster learning across all scales and fields . A learnThe expected outcomes of OH initiatives are health and welfare of humans, animals, plants, and ecosystems, all managed by common health strategies. This ensures healthy food, as well as clean water and air. Transdisciplinarity should result in improved stewardship and compliance, and promote interspecies equity, which would facilitate sustainable benefits for humans from other species (domestic and wild) and their habitats. Furthermore, OH should improve effectiveness across different sectors and at multiple scales. It relies on and results in more efficient communication, thereby generating a higher degree of awareness that can enable rapid detection of illness and consequent action. By having a more inclusive voice for neglected human populations, animals, and environment, OH is intended to widen our usual anthropocentric perspectives and to simultaneously enhance human health. The expected outcomes of OH approaches contribute to the three pillars of sustainability, namely, society, environment, and economy. In this way, the approach can be an instrument to working toward the UN sustainable development goals.Most diseases identified by WHO in their global burden of disease analysis,As demonstrated by the global AIDS response, this inclusive governance challenges current global norms, calls for global accountability, and reveals inextricable links between health, human rights, and social, economic, and political empowerment . By formSuch a change in approach requires resources. Consequently, it is important to demonstrate common interests of economic, environmental, social, and health advocates to provide appropriate funding, albeit under challenging economic constraints . We idenTo achieve systemic and scaled resilience to health challenges, the ultimate task for policy makers and other health professionals is to endorse health of people, animals, plants, and the environment and to achieve equitable and sustainable health outcomes , 28. To The article is the result of a workshop. Writing of the article with equal contribution: SR and BM. Senior author supervising the writing: AL. Organization and moderation of the workshop: BH, AM, and SR. Preparatory presentations for the workshop: BH, CIS, TE, MP, MA, JZ, PD, and AM. Workshop participation and article editing: BH, CIS, MP, MA, JZ, SB, JR, LC, DDM, LRN, MC, MF, FG, VI, DM, HO, MR, RK, and AS.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "To the Editor:Preventing Chronic Disease, was used without proper permission from Dr Donald E. Morisky and coauthors. We regret any problems our article may have caused, and we retract it from the literature.Due to an unintentional error, the MMAS-8 scale in our article, \u201cHealth and Nutrition Literacy and Adherence to Treatment in Children, Adolescents, and Young Adults with Chronic Kidney Disease and Hypertension, North Carolina, 2015\u201d (Nikita Patel, BSPH; Maria Ferris, MD; Eniko Rak, PhDThe University of North Carolina at Chapel Hill School of MedicineChapel Hill, North CarolinaPCD marked this article as retracted on December 23, 2016.Response:"} +{"text": "Urinary stones can cause kidney failure, urinary tract infections (UTIs) and severe abdominal pain, blood in urine and flanks pain. Alhagi has been seen in different regions of Iran, especially the north to the border of central deserts, and also grows in North Africa, Saudi Arabia, Syria, Iraq, Turkmenistan, Central Asia and other countries. Alhagi phytochemical such as flavonoids, flavone glycosides, Alhagidin, Alhagitin, proanthocyanidins, triterpenes, tannins, etc which it can be effective on urinary stones.Alhagi pseudalhagi, is a member of Fabaceae family are known as a painkiller in patients with kidney stones. Another name of Alhagi is manna grass which is plant of 20 to 120 cm height, with green to dark green prickly branches. Length of the thorns varies from 1 to 6 cm, and their angle is almost right. Leaves are oval-shaped with a width of 3 to 5 mm and a length of 10 to 15 mm, and the flowers which usually appear in 2 to 8 numbers in each thorns are red, purple and brown have been completely observed by the authors.None."} +{"text": "The current issue of the International Journal of Telerehabilitation (IJT) contains original research, policy, and a country report (India). A letter to the editor cogently describes the challenges faced by occupational audiologists in the United States, due to the current absence of interstate professional license portability. There is no doubt that the lead article, \u201cUserAuthentication in Mobile Phones and Its Application to Healthcare,\u201d is highly relevant given the current security challenged environment.What do these articles have in common? They collectively describe the current status of telerehabilitation: successes, challenges, and future needs., Electronic Publications Associates at the University of Pittsburgh.In this season of giving thanks, we recognize that the IJT could not be produced without the generous efforts of others. We are grateful to new and returning reviewers; Sections Editor, William E. Janes, OTD, MSCI, OTR/L; colleagues at the Rehabilitation Engineering Research Center on Information and Communication Technology Access at the University of Pittsburgh; and, our publishers, Timothy S. Deliyannides, Director, Office of Scholarly Communication and Publishing, and Head, Information Technology, University Library System, and Vanessa Gabler and Michelle BradburyDid you know recent evidence suggests that expressing gratitude on a daily basis , can benefit physical and psychological health? Yet another reason to give a huge \u201ctele-thanks\u201d to all those who are advancing the status of telerehabilitation.The next volume of the International Journal of Telerehabilitation will be published in Spring, 2018. We cordially invite your 2018 submissions by mid-January 2018, and accept original research, case studies, viewpoints, technology reviews, book reviews, and country reports that detail the current status of telerehabilitation.Sincerely,Ellen R. Cohn, PhD, CCC-SLP, ASHA-FIJT EditorJana Cason, DHS, OTR/L, FAOTASenior Associate Editor"} +{"text": "The graphs themselves are all correct. It is simply the letter labels that are wrong. The panel labels should be a, b, c, d, e, f and not e, d, c, b, a, f.Upon publication of the original article , the autThe corrected Fig."} +{"text": "Following the publication of this article it was bSusana C. P\u00f3voas is erroneously affiliated with the Research Centre in Sport and Physical Activity, Maia Institute of Higher Education, Maia, Portugal. The author\u2019s correct affiliation is with the Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University Institute of Maia, ISMAI, Maia, Portugal.Daniel A. Marinho, affiliated only with the Department of Sport Sciences, University of Beira Interior, Covilh\u00e3, Portugal in the original article , is alsoBoth authors\u2019 affiliations are correctly included in the Author details of this erratum."} +{"text": "Scientific Reports6: Article number: 3676110.1038/srep36761; published online: 12052016; updated: 02092017The original version of this Article contained a typographical error in the spelling of Ali Alsalme, which was incorrectly given as Ali Mohammed Alsalme.In addition, Mohamed F. Al-Ajmi was incorrectly affiliated to \u201cProtein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh-11451, Kingdom of Saudi Arabia\u201d. The correct affiliation for this Author is listed below:Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh-11451, Kingdom of Saudi Arabia.In addition, there was a typographical error in the legend of Figure 7, where:\u201cEffect of ceftazidime on las and pqs systems\u201d.Now reads:\u201cEffect of NS-ZnNPs on las and pqs systems\u201d.These errors have now been corrected in the HTML and PDF versions of this Article."} +{"text": "GBD 2016 Mortality Collaborators. Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390: 1084\u2013150.2017; The full-text version of this Article has been updated so that the list of authors is displayed in the correct order, in line with the pdf version, rather than in alphabetical order. This correction has been made to the online version as of Oct 12, 2017."} +{"text": "AbstractA summary of the species of amphibians and reptiles of the state has been compiled, including their geographic distributions, habitats, and conservation statuses. The herpetofauna of San Luis Potos\u00ed consists of 41 species of amphibians and 141 species of reptiles. San Luis Potos\u00ed shares the highest number of species with Hidalgo and Tamaulipas, and the least number of species with Nuevo Le\u00f3n. In San Luis Potos\u00ed, there are several taxa of particular conservation concern including salamanders, emydid and trionychid turtles, anguid and xenosaurid lizards, and natricid and colubrid snakes. Three physiographic provinces that vary in their temperature and the moisture retention of their soils collections; (3) a thorough examination of the available literature on amphibians and reptiles of the state; and (4) databases from the Comisi\u00f3n Nacional para el Conocimiento y Uso de la Biodiversidad , including records from the following 30 collections:This list of amphibians and reptiles of the state of San Luis Potos\u00ed was compiled from the following sources: (1) our own field work; (2) specimens from the Laboratorio de Ecolog\u00eda \u2013 UBIPRO CASCollection of Herpetology, Herpetology Department, California Academy of SciencesCMNHCollection of Herpetology, Amphibians and Reptiles Section, Carnegie Museum of Natural History \u2013 PittsburghCNARColecci\u00f3n Nacional de Anfibios y Reptiles, Instituto de Biolog\u00eda UNAMEALC Ernest A. Liner Collection of HerpetologyENCB Colecci\u00f3n Herpetol\u00f3gica, Departamento de Zoolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicasENEPI Colecci\u00f3n Herpetol\u00f3gica, Departamento de Biolog\u00eda Experimental, Escuela Nacional de Estudios Profesionales, Unidad Iztacala, UNAMFMNHDivision of Amphibians and Reptiles, Field Museum of Natural HistoryFSM-UFCollection of Herpetology, Florida State Museum, University of FloridaFWMSHFort Worth Museum of Sciences and HistoryLACMCollection of Herpetology, Herpetology Section, Natural History Museum of Los Angeles CountyLSUMZCollection of Herpetology, Museum of Zoology, Biological Sciences Division, Louisiana State UniversityMCZCollection of Herpetology, Museum of Comparative Zoology, Harvard University CambridgeMNHUK Museum of Natural History, Division of Herpetology, University of KansasMZFC-UNAMColecci\u00f3n Herpetol\u00f3gica, Museo de Zoolog\u00eda \u201cAlfonso L. Herrera\u201d, Facultad de Ciencias UNAMMVZCollection of Herpetology, Museum of Vertebrate Zoology, Division of Biological Sciences, University of California BerkeleySDNHMCollection of Herpetology, Herpetology Department, San Diego Natural History MuseumTCWCCollection of Herpetology, Texas Cooperative Wildlife Collection, Texas A&M UniversityTNHCCollection of Herpetology, Texas Natural History Collection, University of Texas AustinTUCollection of Herpetology, Biology Department, Tulane University, New OrleansUAZAmphibians and Reptiles Collection, University of ArizonaUCMCollection of Herpetology, University of Colorado MuseumUIMNHCollection of Herpetology, University of Illinois Museum of Natural HistoryUIUCCollection of Herpetology, Museum of Natural History, University of Illinois at Urbana-ChampaignUMMZCollection of Herpetology, Museum of Zoology, University of Michigan Ann ArborUSNMCollection of Herpetology, Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian InstitutionUTAMMMerriam Museum, University of Texas ArlingtonUTEPCollection of Herpetology, Laboratory of Environmental Biology, Biological Sciences Department, University of Texas - El Pasohttp://amphibiaweb.org) and reptile names follow Amphibian names follow Lampropeltispolyzona for L.triangulum, Chiropterotritonmiquihuanus, Crotalusmorulus, Lampropeltisannulata for L.triangulum, L.annulata for L.triangulum, Amastridiumsapperi, The number of overlapping species with those neighboring states for which a recent checklist exists Hidalgo: was deteEleutherodactylusdennisi), a species not included in this paper since the only record for this species , seems to be a misidentified longipes. AmastridiumsapperiE. was added based on Sceloporuscowlesi was substituted for S.consobrinus based on Leach\u00e9 (pers. comm.), Scincellasilvicola for S.caudaequinae based on Holcosusundulatus for H.amphigrammus based on Lampropeltistriangulum was substituted for L.annulata and L.polyzona based on Xenosaurusnewmanorum was regarded as endemic to Mexico but not to San Luis Potos\u00ed based on Ranacatesbeiana), the Common Four-clawed Gecko (Gehyramutilata), the Common House Gecko (Hemidactylusfrenatus), and the Mediterranean House Gecko (H.turcicus).San Luis Potos\u00ed is home to 182 species of amphibians and reptiles which represent 33 families and 98 genera potentially occurring in San Luis Potos\u00ed was compiled Table , based oThe species accumulation curves for all species, amphibians, and reptiles suggest that the current list of species is close to being the likely species richness for San Luis Potos\u00ed Figure . These cSeventeen of the 41 species of Amphibians that inhabit San Luis Potos\u00ed are endemic to Mexico, two of which are restricted to small areas in the Sierra Madre Oriental around southeastern San Luis Potos\u00ed (Table Crocodylusmoreletii), is widely distributed from Tamaulipas to Central America. Three of the seven species of turtles that inhabit San Luis Potos\u00ed are endemic to Mexico, two of them to eastern Mexico and another is widely distributed in western and central Mexico (Table Ophisaurusincomptus and Lepidophymamicropholis) one is found from southern Tamaulipas to northern Hidalgo (Xenosaurusnewmanorum), another to a small area in Coahuila, Nuevo Le\u00f3n, and San Luis Potos\u00ed (Sceloporusgoldmani), one more to northern Quer\u00e9taro and adjacent San Luis Potos\u00ed (Lepidophymaocculor), and another to a small area in San Luis Potos\u00ed, Quer\u00e9taro, and Hidalgo (Lepidophymagaigeae). Most of the remaining 19 lizards endemic to Mexico are distributed mainly in eastern or central Mexico, in northern Mexico (Holbrookiaapproximans), or in western and eastern Mexico varied among the habitat types. Twenty-nine percent of amphibians in the Chihuahuan Desert were listed in IUCN categories, 72% in the Sierra Madre Oriental, 46% in the subtropics of the Sierra Madre Oriental, and 8% of the generalists. For SEMARNAT categories, 57% of amphibians in the Chihuahuan Desert, 72% in the Sierra Madre Oriental, 46% of the subtropics of the Sierra Madre Oriental, and 23% of the generalists were listed. Thus, for amphibians, species found in the Sierra Madre Oriental are the most threatened whereas the generalists were least threatened. Reptiles showed a slightly different pattern. For the IUCN listings, all habitat types had relatively few species in the protected categories . However, for SEMARNAT, 28% of reptiles in the Chihuahuan Desert, 50% from the Sierra Madre Oriental, 50% from the subtropics of the Sierra Madre Oriental, and 42% of the generalist species were in the protected categories. For reptiles, the conservation status of the species in each habitat type is more evenly distributed across the habitat types than in amphibians.The conservation status of the reptiles and amphibians in each habitat type was examined. For amphibians, the percentage of species in protected IUCN categories (PageBreakHopefully, by establishing this list of herpetofaunal species with their global and country-level conservation statuses will prompt further investigations into the amphibians and reptiles of this state, which could provide the needed information to allow for state specific, or even habitat type, conservation measures to be undertaken. Specific threats known to be present in San Luis Potos\u00ed are deforestation and habitat loss , industr"} +{"text": "The official publication platform for this conference series is SciForum, MDPI, Basel, Switzerland, and Beijing, China. The headquarters of the conference are in the Department of Organic Chemistry, University of Basque Country (UPV/EHU), Biscay, Spain.There is an increasing necessity for multidisciplinary collaborations in molecular science between experimentalists and theoretical scientists, as well as among theoretical scientists from different fields. One of the more important forces driving this necessity is the accumulation of large amounts of data as a result of important advances in Cheminformatics and Molecular Sciences Experimental Techniques of data acquisition in general. In this context, we decided to create the MOL2NET International Conference Series on Multidisciplinary Sciences , and IKERBASQUE, Basque Foundation for Sciences, with the Faculty of Informatics, University of Coru\u00f1a (UDC).http://sciforum.net/conference/mol2net-1). This first conference attracted more than 100 papers and 300+ authors and/or committee members representing 30+ universities of 20+ countries. Some of the world\u2019s top universities and centers represented in the lists of committee members and/or authors were: Harvard Medical School, Boston, MA, USA; Stanford School of Medicine, Stanford, CA, USA; Virginia Commonwealth University (VCU), Richmond, VA, USA; University of Minnesota Duluth, Duluth, MN, USA; Conservatoire National des Arts et M\u00e9tiers, CNAM Paris, France; University of Pennsylvania, Philadelphia, PA, USA; Miller School of Medicine, University of Miami, Coral Gables, FL, USA; EMBL-EBI European Bioinformatics Institute, Cambridge, UK; CAS Chinese Academy of Science, Beijing, China; ZJU Zhejiang University, Hanzhou, China. It is also important to highlight that the second edition of this conference, MOL2NET-02, is being held during all of 2016 and the first month of the 2017 (http://sciforum.net/conference/mol2net-02). The Special Issue of IJMS associated with the second edition of the conference is for 2017. This second edition keeps the modality of online participation and also started with a network of associated workshops (in-person participation) in the USA, Spain, China, and some countries of Latin America as well. MOL2NET-01, the first edition of this conference series, took place in December 2015 ,16,17,18Arabidopsis thaliana. Results to date imply that the genome-wide distribution of CDM changes is not only part of the biological signal created by the methylation regulatory machinery, but ensures the stability of the DNA molecule, preserving the integrity of the genetic message under continuous stress from thermal fluctuations in the cell environment.In one of the papers, S\u00e1nchez and Mackenzie , from thIn another work, Melo et al. , from thA team lead by Syll\u00e1-Iyarreta Veit\u00eda , from thNandy and Basak , from thPastur-Romay et al. , from thAranda et al. reportedDe Juli\u00e1n-Ortiz et al. , from thConcu and Cordeiro , from thThe team of authors led by Consonni and Todeschini , from thThe team lead by Marrero-Ponce , from thBesal\u00fa et al. , from thThe team co-directed by Ul-Haq and Barak , from thRam\u00edrez and Caballero , from thChen et al. , from FuPrismatomeris tetrandra. The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the \u03b2-1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. The authors synthesized and assayed a series of ursolic acid analogues. The authors also reported molecular docking and QSAR analysis of their experimental results. They used several structural, topological and quantum chemical descriptors calculated with semi-empirical quantum chemical methods.Abdullah et al. , from thYang et al. reportedA team lead by Mart\u00edn-Santamar\u00eda , from CeN = 82). Logistic analyses were performed to determine the predictive factors associated with depressive, manic, activation, and dysphoric dimensions.Lastly, a research study lead by Arrasate and Gonz\u00e1lez-Pinto , from th"} +{"text": "Journal of Applied Clinical Medical Physics, we conclude the publication of our eleventh volume. In the past several years we have seen a profound growth in the JACMP. In 2008, the last year that my predecessor, Michael Mills, was Editor\u2010in\u2010Chief, we received a total of 142 submissions, or an average of 35.5 manuscripts per quarter. This number was exceeded by almost 25% during the first three quarters of this year. We are well on our way to receiving over 200 submissions for this calendar year. Our rejection rate remains at approximately 45%, so we anticipate significant growth in the number of manuscripts published in the JACMP.With the publication of this issue of the We are not anticipating a large number of changes going into next year. The following is one important change we are instituting for manuscripts submitted effective January 1, 2011: if any humans are involved in a study, appropriate approval from the author's institutional review board must be obtained. Authors need to indicate in the manuscript that such approval has been obtained. This approval also includes use of patient data such as treatment plans. This requirement is consistent with editorial policies in most other journals. For details about the policy, prospective authors are advised to review the Submission Guidelines.In addition, we are trying to limit the size of the JACMP. Rather than increasing our rejection rate, we are encouraging a limit 5000 words for each article. This length restriction will be a recommendation, not a requirement. Associate Editors and reviewers will be reminded of this length restriction when a manuscript is sent out for review. Authors of manuscripts that are significantly longer than 5000 words will be encouraged to restrict the length, especially by reducing the length of the Discussion section.Finally, when mentioning Associate Editors and reviewers, I would like to acknowledge their difficult and time\u2010consuming work in maintaining the quality of manuscripts we publish in the JACMP. Names of Associate Editors can be found below, and names of reviewers can be found in a Supplementary File.Associate Editors (including Guest Associate Editors) for Volume 11 include the following: Nzhde Agazaryan, Salahuddin Ahmad, John Antolak, Sam Beddar, Pat Cadman, Marco Carlone, Nathan Childress, Geoff Clarke, Laurence Court, Luca Cozzi, Larry DeWerd, Bill Erwin, David Followill, Kent Gifford, Michael Gossman, Rebecca Howell, Geoff Ibbott, Jennifer Johnson, Stephen Kry, James Marbach, Mary Martel, Osama Mawlawi, Charles Mayo, Moyed Miften, Eduardo Moros, Firas Mourtada, Ben Nelms, Jennifer O'Daniel, Tinsu Pan, Niko Papanikolaou, Matt Podgorsak, Joann Prisciandaro, Jim Rodgers, John Rong, Yi Rong, Isaac Rosen, Surendra Rustgi, Bill Salter, Mehrdad Sarfaraz, Jeff Shepard, Chengyu Shi, Alf Siochi, Eric Slessinger, Jason Stafford, Frank Van Den Heuvel, Lu Wang, Chuck Willis, Al Zacarias, and Ron Zhu.Thanks are extended to these individuals and reviewers, and especially to the authors, without whose contributions we would have no journal.George Starkschall, PhDEditor\u2010in\u2010ChiefNovember 15, 2010"} +{"text": "C\u00e9cile Martin is not included in the author byline. She should be listed as the eighth author and affiliated with Kyowa Kirin Pharmaceutical Research, Inc. The contributions of this author are as follows: conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper.http://www.kyowakirin.com/index.html). All named authors are or were employees of Kyowa Kirin Pharmaceutical Research, Inc. or Kyowa Hakko Kirin Co., Ltd., Japan at the time of their involvement in the reported study. Kyowa Hakko Kirin Co., Ltd., Japan provided funding for the research of the study and provided support in the form of salaries for authors SK, TO, SB, RC, BG, TK, GD, CM, JL, LK, TT, and YK, but no individuals employed by the funder, other than the named authors, had any additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the \u2018author contributions\u2019 section.Dr. C\u00e9cile Martin should also be included in the Funding section. The correct Funding information is as follows: This work was supported by Kyowa Hakko Kirin Co., Ltd. Japan ("} +{"text": "Mr. Carsten Hullermann is not included in the author byline. He should be listed as the fifteenth author and affiliated with Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany. The contributions of this author are as follows: Data Curation, Validation, Writing\u2013Review & Editing."} +{"text": "Journal of Applied Clinical Medical Physics, we conclude our twelfth volume. Looking ahead to Volume 13, we will find several changes occurring with the Journal. The first of these changes is in the sponsorship of this periodical. As many of our readers may be aware, beginning on January 1, 2012, the American College of Medical Physics (ACMP), the sponsor of this Journal, will cease to exist, and many of the activities of the ACMP will be taken over by the American Association of Physicists in Medicine (AAPM). Beginning in 2012, the AAPM will sponsor two journals, a scientific journal, Medical Physics, and a clinical journal, the JACMP. Instead of reporting to the ACMP Board of Chancellors, the Journal's editorial board will report to the AAPM Board of Directors. However, you, as readers, will see no change in the nature of the manuscripts published in the JACMP, nor any change in the editorial policy, editorial procedures, or mission of the Journal.With the publication of this issue of the A change that you will see, however, is that, beginning with Volume 13, we will be increasing our publication frequency to six issues per year, rather than four. Increasing our frequency of publication is a move that we have been considering for several years, and is a consequence of the increase in number of manuscripts submitted, and subsequently accepted, for publication. We believe the increase in publication frequency will have several advantages. First of all, the turnaround for accepted manuscripts will be faster. In order to meet our publisher's requirements, the deadline date for acceptance of a manuscript for publication in Volume 13 Number 1, scheduled for publication around February 15, is October 15, 2011. Any manuscripts accepted after that date would be published in Volume 13 Number 2. With our quarterly publication schedule, the publication date would be around May 15; hence, with the increased frequency of publication, the publication would occur one month earlier. A second benefit goes to our advertisers, whose message now can reach our readers six times a year, rather than four times a year. We hope that the decrease in turnaround time, coupled with the increased frequency of the Journal, will prove to be advantageous to both our readers and our advertisers.JACMP. Names of Associate Editors can be found below, and names of reviewers can be found in a Supplementary File.Finally, I would like to acknowledge the difficult and time\u2010consuming work of our Associate Editors and reviewers in maintaining the high quality of manuscripts published in the Associate Editors (including Guest Associate Editors) for Volume 12 include the following: Nzhde Agazaryan, Salahuddin Ahmad, John Antolak, Peter Balter, Pat Cadman, Marco Carlone, Nathan Childress, Geoff Clarke, Laurence Court, Luca Cozzi, Larry DeWerd, Bill Erwin, Kent Gifford, Rebecca Howell, Jennifer Johnson, Tommy Kn\u00f6\u00f6s, Stephen Kry, Harish Malhotra, Osama Mawlawi, Charles Mayo, Moyed Miften, Mike Mills, Eduardo Moros, Firas Mourtada, Ben Nelms, Jennifer O'Daniel, Tinsu Pan, Niko Papanikolaou, Donald Peck, Matt Podgorsak, Joann Prisciandaro, Jim Rodgers, John Rong, Yi Rong, Isaac Rosen, Surendra Rustgi, Bill Salter, Mehrdad Sarfaraz, Jeff Shepard, Chengyu Shi, Alf Siochi, Eric Slessinger, Jason Stafford, Lu Wang, Chuck Willis, Kamil Yenice, Al Zacarias, and Ron Zhu.Thank you to our Associate Editors and our reviewers, and especially to our authors, without whose contributions we would have no Journal.George Starkschall, PhDEditor\u2010in\u2010ChiefNovember 15, 2011"} +{"text": "AbstractSorexaraneus Linnaeus, 1758, inhabiting the territory of Belarus, are characterized by a significant variation in the frequency of Robertsonian (Rb) translocations. The frequency clines for translocations specific of three chromosome races: the West Dvina , Kiev , and Bia\u0142owie\u017ca have already been studied in this territory. In this communication we report new data on polymorphic populations with Rb metacentrics specific of the Neroosa race in south-eastern Belarus, analyse the distribution of karyotypes in southern and central Belarus and draw particular attention to the fixation of the acrocentric variants of chromosomes in this area. The results show that certain Rb metacentrics specific of the Neroosa, West Dvina, Kiev, and Bia\u0142owie\u017ca races are absent in many polymorphic populations. Thus, the karyotypic differentiation of S.araneus in the studied area is determined by unequal spread of different Rb translocations and by fixation of acrocentric variants of specific chromosomes.The common shrews, Sorexaraneus Linnaeus, 1758, a species inhabiting Eurasia, is a model object for population genetic studies due to its exclusive chromosomal polymorphism and sex chromosomes are characteristic of species S.araneus , while ten autosomal arms can be presented as acrocentrics or be fused as metacenetrics or as arms of metacentrics .The common shrew, enetrics . The desS.araneus is a subdivision of populations into chromosome races. \u201cA chromosome race of Sorexaraneus is defined as a group of geographically contiguous or recently separated populations which share the same set of metacentrics and acrocentrics by descent\u201d (S.araneus differ in the composition and numbers (one\u2013five pairs) of metacentrics, which were formed by Robertsonian (Rb) translocations involving 10 pairs of acrocentric chromosomes, g, h, i, k, m, n, o, p, q, and r is considered as initial in chromosomal evolution of S.araneus (Rb translocations are referred to as \u201crace-specific fused chromosomes\u201d (or \u201crace-specific metacentrics\u201d) (Rb translocations are fixed), while polymorphism for 2\u20135 translocations was revealed in majority of chromosome races . MonomorRb translocations may have occurred in isolated small-size populations, for example, in glacial refugia. The data on mtDNA polymorphism in some European species of small mammals, including species of the genus Sorex, testify to the existence of multiple glacial refugia in Mediterranean and central Europe make contact, narrow hybrid zones (0.5\u20135 km) are formed . If race0\u2013100 km .PageBreakg/m, hi, k/o, n, p, q, r) and Turov races were described in the vicinities of Bobruisk and Turov towns, respectively inhabitsp, q, r) , 2016. Tectively .Rb metacentrics, similar to the clinal variation in wide hybrid zones, was observed in the polymorphic populations of the Kiev, Bia\u0142owie\u017ca, West Dvina, and Borisov races in Belarus. Karyotypes with ten pairs of acrocentric chromosomes were found in some of these polymorphic populations in July\u2013September, 2014 and in September, 2015 . Our karyological data on 290 shrews trapped in 2009\u20132013 helped to identify three Rb metacentrics, hi, kr and mn ; however, other two metacentrics of this race, go and pq, have not been found at the sites studied. The Rb translocation hi is fixed in all the examined samples, and chromosome arms k, r and m, n occur both as metacentric and acrocentric morphs were found in two samples from Rechitsa and Bragin districts (nos. 6 and 7).Karyotyping of hs Table . The kr PageBreakRb metacentrics of the Kiev race , hi and ko, were observed , two g/r, hn, ik, m/p), hn and ik, were found were revealed in populations southwards of the town of Borisov , however, the frequency of the gm metacentric occurred to be lower than in the samples from the Ukraine and the shrews with metacentric of the Kiev race (ko) were found in samples from Rechitsa and Bragin districts, and hybrid individuals with metacentrics of both the races were found in the vicinity of Rechitsa city .Rb metacentrics of the Kiev and Bia\u0142owie\u017ca races: simple heterozygotes and complex heterozygotes , were revealed along the Ptich River and on the south bank of the Pripyat River, close to PageBreakthe confluence of the Pripyat and Uborot\u2019 Rivers . The low fitness of hybrids leads to the decrease of metacentric frequency. This phenomenon is called \u201cacrocentric peak\u201d (1) Hybridization between metacentric races which differ for the arm combinations of ic peak\u201d .2) Hybridization between metacentric races and an acrocentric race that existed in the Dnieper basin in the past .Our hypothesis about the existence of acrocentric race in the present-day Belarus or neighbouring territory during the Last glacial maximum does not contradict the paleontological and paleobotanic data: fossil remains of the common shrew were found in the Middle Dnieper basin and a foS.araneus in the low Dnieper and Pripyat basin is determined by unequal spread of different Rb translocations and by fixation of acrocentric PageBreakvariants of the particular chromosome arms. Each of four groups of the polymorphic populations possessing metacentrics, which are specific of the Neroosa, West Dvina, Kiev, and Bia\u0142owie\u017ca races, consists of two subgroups: 1) polymorphic populations with all Rb metacentrics of the initial race, irrespective of their frequencies . According to the definition of a chromosome race as \u201c \u2026 populations which share the same set of metacentrics and acrocentrics by descent\u201d by acrocentric variant of the arms o and r were recognized as the Ammarnas and Hattsjo races by acrocentric variant of arms n and o was recognized as the R\u00fcgen race The absence of metacentrics The abseChromosome race: Gomel\u2019 (Gm)af, bc, g, hi, jl, k/r, m/n, o, p, q, tuKaryotype: XX/XY1Y2, 52\u00b025'29\"N, 30\u00b052'31\"E.Type locality: vicinity of Gomel\u2019 city, Belarus, Distribution range: An area between Dnieper and Sozh Rivers, Gomel, and Rechitsa district; to the south of Rechitsa city to the latitude of Bragino city. The western boundary of the range lies along the west bank of the Dnieper River, approximately at the longitude of Rechitsa city. The other boundaries are not determined.Rb metacentrics characteristic of the Kiev race occur only in populations to the south of the Pripyat River All the three All the Chromosome race: Svetlogorsk (Sv)af, bc, g, h/i, j/l, k/o, m, n, p, q,\ufeff \ufeffr, tu ; the low Berezina basin to the vicinity of Parichi and Zhlobin cities to the north, from the east bank of the Ptich River and to the west bank of the Dnieper River.gr and mp, specific of the Bia\u0142owie\u017ca race, in S.araneus populations inhabiting the territory along the Ptich River allows us to recognize these populations (Table (3) The absence of metacentrics Chromosome race: Oktiabr\u2019skiy (Ok)af, \ufeffbc, g, h/n, j/l, i/k, m, o, p, q, rKaryotype: XX/X Y1Y2, 52\u00b034'26\"N, 28\u00b044'37\"E.Type locality: Rozhanov settlement, vicinity of Oktiabr\u2019skiy town, Belarus Distribution range: Southwestern Belarus, territory along the Ptich River, approximately to the latitude of Osipovichi city to the north. The western boundary is not determined. Easternmost site for shrews of this race is on the east bank of the Berezina River. The southern boundary extends along the south bank of the Pripyat River from Turov city to the confluence of the Ptich and Pripyat Rivers.Rb translocations in definite parts of the S.araneus range is very important for study of intraspecies structure of the S.araneus. Unequal spread of different Rb translocations and fixation of acrocentric variants of particular chromosome arms observed in each of these groups is an interesting example of karyotypic differentiation in populations of the common shrew.Now, 74 chromosome races of the common shrew (including 49 polymorphic ones) are known , however"} +{"text": "The Fourth Congress of the Romanian Society of Cataract and Refractive Surgery, connected with the Annual Conference of the Romanian Retina Society took place in the period 22-25 of June 2017, in Eforie Nord.The association of these two conferences, already a tradition, was again a great success, with an audience of more than five hundred ophthalmologists from Romania and from abroad.The event started on Thursday with an interesting symposium about the role of aflibercept in retinal pathology. Horia Stanca, MD, PhD, and Prof. Mihnea Munteanu, MD, PhD, shared their experience with this type of treatment.The Conference continued with three very interesting lectures: Assoc. Prof. Florian Balta talked about vitamin D and retina, Daniel Branisteanu, MD, PhD, presented an update about the surgical treatment in retinology and Horia Stanca, MD, PhD, approached a very difficult issue: education in ophthalmology, talking about his experience with the educational system for residents in the USA.The following day, the Congress of Romanian Society of Cataract and Refractive Surgery began. There were two days with a very dense schedule, very interesting topics being approached during the sessions: Ngenuity 3D Visualization System Platform, both for anterior and posterior pole surgery, new types of premium intraocular lenses, the role of vitreoretinal surgeon in managing ocular trauma, premium personalized intraocular lens and others.The session about nightmares in ophthalmology was very much appreciated, during which, experienced surgeons shared their experience with very complicated cases.The international participation was important, with interesting presentations of Prof. Usha Chakravarthy - Belfast \u2013 on OCT, Juergen Beierl on Refractive Corneal Topography and Prof. Sorcha Ni Dhunhgheill \u2013 Antwerp - on cataract surgery in children, bag in the lens technique.An important event that also took place during this Congress was the election for the Board of Romanian Society of Cataract and Refractive Surgery. Prof. Calin Tataru, MD, PhD, the leader of this Society the last four years, presented a scientific and financial audit. The overall conclusion was that this was a remarkable period, with many achievements: four Congresses of the Society, the joint with the Conference of Romanian Retina Society, the print of the Guide for Cataract Surgery and many others.The delegates appreciated very much the activity of the former President, so, after the voting, Prof. Calin Tataru, MD, PhD, remained President of Romanian Society of Cataract and Refractive Surgery for the next four years. He suggested and the delegates approved that the former Secretary and Treasurer would remain in duty. Musat Ovidiu, MD, PhD, and Madalina Serban, MD, PhD, were confirmed as Secretary and Treasurer by the delegates.Finally, a vote for two vice presidents established that Dorin Nicula, MD, PhD, and Mihail Zemba, MD, PhD, would join the Board of Romanian Society of Cataract and Refractive Surgery for the next four years. The Editorial Board of Romanian Journal of Ophthalmology wishes great success to all of them.Editor-in-ChiefMihail Zemba, MD, PhD"} +{"text": "In this paper, some properties of the interior of positive dual cones are discussed. With the help of dilating cones, a new notion of inner superefficient points for a set is introduced. Under the assumption of near cone-subconvexlikeness, by applying the separation theorem for convex sets, the relationship between inner superefficient points and superefficient points is established. Compared to other approximate points in the literature, inner superefficient points in this paper are really \u2018approximate\u2019. Rong and Wu =\u2205. By , since \\nd, from and ). From , ProposiC-subconvexlike, and B is a bounded base of C, then C is empty, however, In this paper, some properties for the interior of positive dual cones were studied. Using the dilating cones, we introduced a new notion of inner superefficient points, which has a nice property (see Theorem"} +{"text": "Background: In the present study, we explored the associations between hypomania, symptoms of depression, sleep complaints, physical activity and mental toughness. The latter construct has gained interest for its association with a broad variety of favorable behavior in both clinical and non-clinical samples.Subjects and Methods: The non-clinical sample consisted of 206 young adults . They completed questionnaires covering hypomania, mental toughness, symptoms of depression, physical activity, and sleep quality.Results: Higher hypomania scores were associated with higher mental toughness, increased physical activity, lower symptoms of depression and lower sleep complaints. No gender differences were observed. Higher hypomania scores were predicted by higher scores of mental toughness subscales of control and challenge, and physical activity.Conclusion: The pattern of results suggests that among a non-clinical sample of young adults, self-rated hypomania scores were associated with higher scores on mental toughness and physical activity, along with lower depression and sleep complaints. The pattern of results further suggests that hypomania traits are associated with a broad range of favorable psychological, behavioral and sleep-related traits, at least among a non-clinical sample of young adults. For at least three reasons there is growing interest in the mood state of hypomania: First, hypomanic states and bipolar disorders may be underdiagnosed , 2010: AMore specifically, the dimensionality of increased mood has gained particular attention. Further studies showed that higher scores of hypomania were associated with higher scores of self-efficacy, exploration behavior, pain tolerance, and coping, along with higher physical activity , more unWhile there is extant literature as regards the associations between dimensions of increased scores of hypomania and romantic love states, increased sleep, and lower scores of depression and anxiety, surprisingly and to the best of our knowledge, only one study focused on the association between the dimensionality of hypomania and physical activity, while the association between hypomania scores and mental toughness is fully unexplored so far. However, we claim that focusing on both physical activity and mental toughness is justified for the following reasons: As regards physical activity, there is evidence that inactivity has become the new \u2018smoking\u2019; in other words, inactivity has become the main factor for the emergence of non-communicable diseases. Further, reviews and meta-analyses showed tMental toughness is a psychological concept to describe a person\u2019s ability to cope with difficulties and to achieve self-defined aims . SpecifiWe hold that shedding some more light on the relationship between dimensions of hypomania, physical activity and dimensions of mental toughness is important, as a deeper understanding may serve to underpin the analysis of certain facets of human behavior. Further, previous research investigThe following three hypotheses and two research questions were formulated. First, following a previous study , we expeStudents of the Hamadan University of Medical Sciences were approached to participate in the present questionnaire-based study on the relationship between hypomania, mental toughness, physical activity, depression, and sleep. All participants were fully informed about the study aims, the confidential nature of the data gathering, and the secure data protection. Afterward, all participants signed the written informed consent. Next, clinical psychologists performed a brief psychiatric interview participated in the study; 15 were excluded due to psychiatric issues , and 42 declined to participate in. No age difference between male and female participants was observed .During the spring semester 2016, a total of 263 students of the Hamadan University of Medical Sciences were approached, and 206 was applied . The ISIwww.ipaq.ki.se. However, in the present study, we collapsed the data to a composite score; the reason was that scores of vigorous-intensity activities were rarely reported and that preliminary calculations showed that differences between walking and moderate-intensity activities were very small.To obtain information on physical activity, the short version of the International Physical Activity Questionnaire (IPAQ) was used. This questionnaire was developed by a working group initiated by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). The purpose of the questionnaire is to provide an estimate of a weekly physical activity time. Further, results from twelve countries demonstrate that the IPAQ has comparable reliability and validity to other self-report measures of physical activity . The shot\u2019s were < 1.0, p\u2019s > 0.1; thus, gender was not introduced as a possible confounder. Next, we performed a series of non-linear calculations between hypomania scores and scores of mental toughness, physical activity, and symptoms of depression, and the introspection showed no non-linear associations. Thus, only linear correlations were performed.Preliminary calculations: First, we performed a series of t-tests to compare data between male and female participants; all \u00ae 24.00 for Apple Mac\u00ae.First, a series of Pearson\u2019s correlations were performed between scores of hypomania and mental toughness, symptoms of depression, sleep complaints and physical activity. Next, to predict hypomania scores, a multiple regression analysis was performed with mental toughness traits, depression, sleep and physical activity as predictors. The nominal level of significance was set at \u03b1 \u2264 0.05. All computations were performed with SPSSTable 1 reports all correlational computations and the descriptive statistics for the scores of hypomania and mental toughness (MTQ48), symptoms of depression (BDI), sleep complaints (ISI), and physical activity (PA).Higher scores in hypomania were associated with higher scores in mental toughness, and more specifically with the overall score and with all subscales.Higher scores in hypomania were associated with decreased sleep disturbances (ISI), and symptoms of depression (BDI), but with higher physical activity scores (PA).R = 0.497; R2 = 0.243, Durbin\u2013Watson coefficient = 1.76) were predicted by higher scores of Challenge and Control , and higher physical activity scores , while all other predictors were excluded from the equation .To predict hypomania scores, a multiple regression analysis was performed with hypomania scores as dependent variable, and MT traits, sleep disturbances, symptoms of depression, and physical activity as predictors. Higher hypomania scores , though the inherent statistical algorithms of multiple regression analyses are such to favor those predictors with higher correlation coefficients.The present results also answer the second research question: Higher hypomania scores were predicted by higher scores of Challenge and Control, along with higher physical activity scores. We also note that The quality of the data does not allow a deeper introspection into the underlying psychological mechanisms of why hypomania and mental toughness might be associated, though we advance the following hypotheses: typical items of the hypomania questionnaire cluster Despite the novelty of the data, several limitations warrant against an overgeneralization of the results. First, we assessed young adults, who by definition do not represent people of lower and higher age, and above all not people with mental health issues. In this view, both inclusion and exclusion criteria were such to exclude participants with psychiatric disorders. While from a scientific point of view, it would have been also important to assess such participants, we decided to exclude them, as we wanted to investigate explicitly a non-clinical sample. Second, we did not distinguish between \u2018bright\u2019 and \u2018dark\u2019 side hypomania categories, as proposed by other studies , though Among a sample of young adults, higher hypomania scores were associated with higher scores of mental toughness and physical activity. The results add to the current literature in showing that traits of hypomania are associated with favorable traits such as mental toughness and increased physical activity.Study design: LJ, AR, MH, MA, DSB, AS, SS, HB, MG, and EH-T and SB. Data gathering: LJ, AR, MH, MA, DSB, AS, SS, and HB. Data analysis: AR, DSB, MG, EH-T, and SB. Interpretation of the data: LJ, AR, MH, MA, DSB, AS, SS, HB, MG, EH-T, and SB. Writing the first draft: AR, MA, DSB, MG, EH-T and SB. Integration of the authors\u2019 comments: AR, MA, DSB, MG, EH-T, and SB. Final manuscript: LJ, AR, MH, MA, DSB, AS, SS, HB, MG, EH-T, and SB.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Since the turn of the twenty-first century, competency-based medical education (CBME) has become a dominant approach to postgraduate medical education in many countries. CBME has a history dating back half a century and is rooted in general educational approaches such as outcome-based education and mastery learning. Despite controversies around the terminology and the CBME approach, important national medical regulatory bodies in Canada, the United States, and other countries have embraced CBME. CBME can be characterized as having two distinct features: a focus on specific domains of competence, and a relative independence of time in training, making it an individualized approach that is particularly applicable in workplace training. It is not the length of training that determines a person\u2019s readiness for unsupervised practice, but the attained competence or competencies. This shift in focus makes CBME different from traditional training. In this contribution, definitions of CBME and related concepts are detailed. Competency-based medical education (CBME) or training (CBMT) has become widely used terminology since the turn of the twenty-first century. Despite its ubiquitous use, there is variation in the use of the terminology and related concepts. In this entry a brief historical overview of the concept is provided, followed by a focus on a clear justification and definition of CBME, competence, competency, and closely related concepts. In 1949, long before the term \u201ccompetency-based\u201d education was being used in medical or other areas of education, educational psychologist Ralph Tyler sowed its first seeds in what has become known as the \u201cTyler rationale\u201d is a health-professional who can practice medicine at a defined level of proficiency, in accord with local conditions, to meet local needs\u201d .As competency-based medical education is outcome-based, a focus of CBME on postgraduate training has been dominant. In western countries, unsupervised practice of healthcare, the dominant outcome of the training of physicians, is almost exclusively the prerogative of medical specialists after postgraduate training, which now includes primary care. CanMEDS framework project in the 1990s . T. TCanMEDhe 1990s , 13], to to10] tofacets of competence, which is actually a better wording than competencies ..facets oEPAs have been proposed in a wide range of specialty programs, including pediatrics, psychiatry, internal medicine, anesthesiology, geriatrics, surgery, pulmonary and critical care, family medicine and emergency medicine , 35], , , 37], , , 39], , , 41]. . 41]. Another recent concept connected with CBME is that of \u201cmilestones.\u201d En route to competence, trainees develop progressively in a way that can be defined as stages or performance levels. In the 1980s, Dreyfus and Dreyfus defined five stages in the development of skill: Novice, Advanced Beginner, Competent, Proficient, and Expert . These hst century , i, i48], i century , 53]..st centuAnother issue that will ask attention is the continuum of medical training. While a century ago the basic medical degree was sufficient for independent practice of most medical trainees, now it has become embedded in a continuum . ContinuThis article is based to a large extent on Ten Cate O, \u201cMedical Education, Competency-Based\u201d in the Wiley Blackwell Encyclopedia of Health Illness, Behavior, and Society by Cockerham WC, Dingwall R and Quah, SR (Eds), 2014 John Wiley & Sons, Ltd (pp 1329-1335). Permission was obtained to republish this entry.The author declares that he has no competing interests."} +{"text": "Val Vallyathan died in a tragic accident Friday, July 23, 2010 while visiting family in New Jersey. His colleagues at NIOSH, Morgantown, WV are stunned by his sudden death.Val was married for 45 years to Usha, and they were blessed with two children, Sanjay and Veena, and two grandchildren.Val received his B.Sc. (Honors), M.Sc., and Ph.D. degrees at Maharaja Sayajirao (M.S.) University of Baroda, India. He next held several academic and research and teaching positions at Maharaja Sayajirao University, the University of Baroda, the University of Guelph (Canada), the University of Vermont, and the Institute for Muscle Disease. Val joined NIOSH in 1979 and had been a leading researcher on the Morgantown campus ever since. He served as an Advisor to many university graduate students and postdoctoral fellows at the Maharaja Sayajirao University, the University of Vermont, West Virginia University and NIOSH.At NIOSH Val was a Research Physiologist and Team Leader in the Pathology and Physiology Research Branch (PPRB) of the Health Effects Laboratory Division. In fact, Val was trained primarily as an experimental pathologist, and his primary research interests lay in occupational respiratory diseases. After his retirement in October, 2009, Val came back to PPRB as an Expert Consultant; he was unable to cut his ties to his research activities, and probably would have never really retired and left his research.In addition to his duties at NIOSH, Val held several Adjunct Professorships at West Virginia University, Morgantown, WV, in the Departments of Pathology, Basic Pharmaceutical Sciences, and Anatomy.Val's influence on occupational health research was widely acknowledged and reached around the world. Of the many conferences he organized or played a significant role in, he would be most proud of the four international conferences on oxygen and nitrogen free radicals, the last one being held in October, 2009. Other conferences with which he was involved, both within and outside of NIOSH, were equally relevant, timely and successful.Nominated 17 times for Alice Hamilton and Charles C. Shepard Awards for \"Best Paper of the Year\" in NIOSH or CDC, respectively. Val received the Hamilton award in 1999 and 2001 and honorable mentions in other years.Val figure was inteIn addition to holding one patent, Val published extensively. He served as a book editor, guest editor or chapter or review contributor for many volumes. In addition, he authored at least 376 full publications in scientific journals, with another dozen or so invited articles. He has published at least 198 conference presentations and abstracts, with 5 papers in preparation at the time of his death. What we noticed as we reflected on Val's tenure at NIOSH was the remarkable diversity of his interests and curiosity. For example, he has published papers characterizing the effects, mechanisms of action, and possible approaches for preventing disease from the following array of toxic agents: nanotubes, metal particles, asbestos, silica, quartz, cigarette smoke, agricultural dust, coal dust, reactive oxygen species, grape dust, citrus dust, diesel exhaust, cadmium, iron, mercury, cumene hydroperoxide, toluene diisocyanate, welding fume, arsenic, chlorogenic acid, lipopolysaccharide, vanadate, chromium, nickel, eugenol, nylon flock, volcanic ash, and talc. His work also paid much attention to pathways involved in apoptosis, the respiratory burst and surfactant's role in the lungs. Of these subjects his greatest scientific contributions were to the understanding of silicosis and the roles of free radicals in lung disease.The above facts are a dry, statistical summary of the scientific life of Val Vallyathan. They do nothing to honor him as a person, friend and colleague. Val was universally liked by everyone; he had malice for no one. It was always enjoyable to be in Val's company because he was respectful, engaging and pleasant. He was open, honest and unpretentious, despite his accomplishments. Rarely did he ever complain, but, if he did, he did so with elan, wit and wisdom, making us all laugh and ever aware of the special person he was.We have lost a dedicated and committed lung researcher and friend. His is a huge legacy."} +{"text": "We are HIV. Our family is ancient.Out of Africa,Monkey to man,From the trees and forests,To the towns and cities.We are here.For we are HIV, we are legion.Our children are billions,Our home, in your defenses,In your blood, your brain,Your saliva, your semen.We are everywhere.For we are HIV, we are immortal.We are part of you,And you of us,We live with you, butMay not die with you.We go on.For we are HIV, we are travelers.From lover to lover,Mother to baby,Donor to blood bank,Blood bank to patient,We follow you.For we are HIV, we evolve.NRTIs, NNRTIs, PIs, INIs,New designs, new drugs,Bring it on, bring it on,Q151M, K103N, L90M.We adapt, we survive.We are HIV. We consume.Your resources, your time,Your hope, your lives,Your new drugs are easy.Where are your vaccines?Can you stop us? We will see."} +{"text": "Surprisingly, however, these authors did not recognize that there is a third major mechanism for human contact with plant allergens: ingestion. In an article published in Air Quality, Atmosphere & Health, I (In their article, ealth, I proposedealth, I .2, on plant food allergens, especially their relative concentrations.I agree that the plant biology aspect of climate change and human health is underappreciated, and I also strongly support"} +{"text": "University Hospital, Uppsala, Sweden is incorrectly used in the affiliations. It should be replaced with Uppsala University, Uppsala, Sweden."} +{"text": "In this study the authors have prospectively analyzed the results of 40 samples from tomato, orange, lemon, and mandarin juices. Ten samples of 100 ml were collected from four juice groups. Citrate, oxalate, calcium, phosphorus, magnesium, sodium, potassium, chloride, and pH levels were examined in all samples. The same values were also examined after the samples were stored at 4\u00b0C for 1 week.P < 0.001, P < 0.001, and P < 0.001, respectively), higher level of magnesium , and lower level of sodium were found as compared to orange, lemon, and mandarin juices. No differences were found with regard to calcium, potassium, phosphorus, chloride, and pH in these juices.In fresh juice groups, in tomato juice statistically higher level of citrate , higher level of magnesium , and lower level of sodium were found as compared to orange, lemon, and mandarin juices. No differences were found with regard to calcium, potassium, phosphorus, chloride, and pH in these juices.Similarly, in stored juice groups, in tomato juice statistical higher level of citrate , were found in tomato juice as compared to orange, lemon, and mandarin juices. Higher level of oxalate was found in stored group as compared to fresh juice group (P <0.005).In fresh juice group, statistically lower level of oxalate through the gastrointestinal tract. More than 90% of the citrate that is absorbed is metabolized. Approximately 10% is excreted in urine without being metabolized.[In this study, authors have shown higher level of citrate in tomato as compared to citrus plants, which are natural sources of citrate. In addition, the lower level of oxalate as compared with that in citrus fruits is a noteworthy advantage. The high level of magnesium and low level of sodium and oxalate, particularly in fresh tomato juice, is also remarkable. In terms of calcium and pH levels, no significant differences were observed between tomato and citrus fruits. The amount of oxalate was shown to increase in stored tomato juice.All above factors, that is higher citrate and magnesium levels as well as lower sodium and oxalate levels help in prevention of stone formation. Fresh tomato juice is well tolerated and inexpensive. The results of this study indicate that, following further human studies, fresh tomato juice may be recommended instead of pharmacologic potassium citrate for prophylactic purposes in mild to moderate hypocitraturic recurrent nephrolithiasis.Interestingly, in India, there is widespread misconception among general population as well as among general practitioners that tomatoes are high in oxalate, and predispose to stone formation. This study convincingly demonstrates the truth to be just the opposite, and tomato juice may prove to be the treatment of choice in stone prevention."} +{"text": "Following the publication of this article , it was The authors declare that they have no competing interests.All authors participated at the EUROPRISE conference as to be able to report on it. MB, AC, KDC, WDH, TD, SD, KG, DH, JH, KK, LM, PP, MR, JS, PS, AS, HU, MJVG, and CW were in charge of the writing of dedicated chapters covering the different sessions of the conference. GS, BW and RS organized the sessions and the writing. Together with PB they wrote, corrected and revised the manuscript. All authors read and approved the final manuscript."} +{"text": "University Hospital, Uppsala, Sweden is incorrectly used in the affiliations. It should be replaced with Uppsala University, Uppsala, Sweden."} +{"text": "A comprehensive book, probably first time in India, on a wide variety of legal issues concerning medical profession which is meant to provide necessary legal knowledge for solving day-to-day problems of doctors, nursing homes, hospitals, blood banks, and other medical establishments.It is an aid to the medical profession for protection against exploitation and harassment. The topics covered in this book include Medical Council of India, dental/homeopathy/Indian medicines/nursing/pharmacy/rehabilitation councils. MTP, PCPNDT, transplantation of human organs, mental health, blood banks, biomedical waste, registration of births and deaths, epidemic diseases, consumer protection, human rights, right of information, electricity, development authority, municipal tax, minimum wages and related labor laws, employee's provident fund and related schemes, criminal procedure code, income tax search, and surveys with PAN/TAN, professional indemnity insurance, health insurance, Supreme Court judgments, forms for registering complaints against harassment with Lok-Ayukta and National Human Rights Commission, Fundamental Rights, citizenship, Red Cross, etc.This book also contains copies of official documents which are useful to settle day-to-day problems. However, these documents mainly relate to state of Uttar Pradesh, but their application can be extrapolated to other states as well as most of the laws are similar if not identical in almost all the states.The writer is himself a doctor and hence is well aware about the ignorance of doctors in general about their responsibilities and rights while being subjected to laws of the land. In this context, the book is a legal companion for all the people connected with medical profession. It will serve as a reference book whenever faced with any legal or administrative problems."} +{"text": "Objective: The object of this study was to develop a simple and inexpensive test for detection of bacterial vaginosis (BV) in pregnant patients and to test its accuracy in a clinic population.\t\t\t\t\tMethods: We developed a modified proline aminopeptidase (PAMP) assay to detect BV and compared the results of the assay with the clinical diagnosis of BV.\t\t\t\t\tResults: The results of the PAMP assay in 55 asymptomatic and 50 symptomatic subjects significantly correlated with a clinical diagnosis of BV. The prevalence of BV in the asymptomatic population was 42% (PAMP assay) and 38% . In the symptomatic population, it was 50% (PAMP assay) and 54% . The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the PAMP assay were 86, 85, 86, 78, and 91%, respectively, in asymptomatic patients and 89, 96, 92, 96, and 88%, respectively, in symptomatic patients.\t\t\t\t\tConclusions: The modified PAMP assay, which we describe, met our goals for simplicity, cost, and accuracy. We feel it could be best used as a screening test for BV in asymptomatic pregnant patients."} +{"text": "This report from the International Summer School \u2018From Genome to Life\u2019, held at the Institute d'Etudes Scientifiques de Carg\u00e8se in Corsica in July 2002, coversthe talks of the invited speakers. The topics of the talks can be broadly groupedinto the areas of genome annotation, comparative and evolutionary genomics, functionalgenomics, proteomics, structural genomics, pharmacogenomics, and organellegenomes, epigenetics and RNA."} +{"text": "Two households, both alike in dignity, In fair Genomics, where we lay our scene, , From ancientgrudge break to new mutiny, When \u2018being\u2019 drives a fly-man to blaspheme. Fromforth the fatal loins of these two foes, Researchers to unlock the book of life; Wholemisadventured piteous overthrows, Can with their work bury their clans' strife. Thefruitful passage of their GO-mark'd love, And the continuance of their studies sage,Which, united, yield ontologies undreamed-of, Is now the hour's traffic of our stage;The which if you with patient ears attend, What here shall miss, our toil shall striveto mend."} +{"text": "Toward this end, the HHI has compiled data in areas including indoor air, drinking water, building and remodeling, housekeeping, and energy efficiency on its website, Information is presented in seven topic categories: Air, Building, Design, Energy, Health & Safety, Materials & Furnishings, and Water. Each topic page presents resources organized by four information types: Reviews; Tools; Articles, Hints, & Tips; and Books & Videos. The Reviews category links to overviews of products inspected by HHI that perform well in such areas as safety, energy use, allergen reduction, and use of chemicals. The Tools category lists products that can be used in building or remodeling to make a healthier home. These include paints and coatings, lighting fixtures, indoor air cleaners, and pest control strategies.Green Building A to Z (an introduction to sustainable housing), Green Clean (a primer on eco-friendly housekeeping), and The Mold Survival Guide . Visitors can also consult the \u201cHHI-pedia,\u201d a list of definitions for terms used in green building and housekeeping.The Articles, Hints, & Tips section provides information on new green products, how to choose sustainably produced building materials, green roofs, and energy efficiency. The Books & Videos page lists educational materials such as"} +{"text": "Information collected by the CD is available through the top menu bar of PAHO\u2019s Health Surveillance and Disease Prevention and Control website.Besides information on diseases such as cholera, acute respiratory infections, and anthrax, the website provides information on mosquito-borne diseases such as dengue, malaria, West Nile virus, and yellow fever. Sections on each disease link to resources for disease surveillance, reports on the history of each disease, profiles of the disease in countries where it is occurring, and statistics on incidence and mortality. Each section also links to any available epidemiological surveillance systems and to laboratory networks established by PAHO for each disease. Visitors will also find resources for prevention, control, and educational efforts, including field guides, materials for families and communities, policy documents, overviews of global disease control strategies, travel advisories, journal articles, and bibliographic databases."} +{"text": "Cecil Studios in Florence, Italy. The New York Academy of Art won the support of Andy Warhol: \u201cThe course of art history,\u201d he said, \u201cwould be changed if one thousand students could be taught Old Master drawing and painting techniques\u201d (In 1982, Lack coined the term \u201cClassical Realism\u201d because as he put it, \u201cAny 20th century painting that suggests a recognizable object, however crudely or childishly rendered, qualifies as \u2018realistic.\u2019 Obviously, the simple word \u2018realism,\u2019 when applied to painting\u2026is no longer meaningful\u201d (A painter in the tradition of Spanish realism, Francisco Roa was born in Guadalajara, Spain, and moved to Madrid at age 18 to study at the Universidad Complutense and the Academia Pe\u00f1a. He has received considerable recognition at home, exhibiting in Madrid, Barcelona, and Granada. In 1993, he took his works to Lisbon and Miami, and a year later, to New York and Atlanta.Extremely careful with detail, Roa, like many of his contemporaries, conveys an individual perception of reality, positioning everyday objects deliberately, proposing his own space and time. Sands Flowers, on this month\u2019s cover, first exhibited in the United States in 1994, is a characteristic still life.Against a vacant background vaguely reminiscent of sand, the artist composes a geometric ensemble to anchor his main object of interest, a glass vessel filled with natural elements past their prime. The board base, stacked on the left, breaks up the horizontal field. The metal circle, weathered and discolored, is slightly off center, the backdrop deliberately smudged. Inside the glass lie red petals, crinkled and lifeless, the detritus of beauty. Crammed in near the top is a hornet\u2019s nest, and out of each side, dried blooms jut pathetically, their stems distorted and petals curled.\u201cAll forms of beauty, like all possible phenomena,\u201d wrote Charles Baudelaire in his On the Heroism of Modern Life, \u201ccontain an element of the eternal and an element of the transitory\u2014of the absolute and the particular\u201d (The eternal and the absolute are elements artists have sought in the formalities of realism and the fragments of abstraction, on the same pathway, 1 step forward, 2 steps back; and scientists likewise, for rarely does excellent science or art occur without reference to past knowledge and principle.In Sands Flowers, Roa probes the precariousness of existence, space and time, and life and death. His realistic representation of natural objects in decline provokes speculation\u2014not only on the passage of time and inevitability of death, but for us, also on disease, which unduly hastens the process. In an unending circle, old scourges become new, among them tuberculosis, a hornet\u2019s nest of multiple drug resistance, and now extensive resistance to second-line drugs, raising the specter of potentially untreatable disease. Roa sought essence in the staying power of exacting detail. In science too, on the same pathway, sometimes solutions lie simply in the core values: treatment standards, effective precautions, improved technology, better medicines, vaccines, and diagnostic tests ("} +{"text": "After the publication of this manuscript , a collaMM, AS, MAC, and JS carried out the sampling and infection experiments. JS made the cDNA libraries, oversaw the sequencing, participated in the assembly and annotation of the EST datasets, analyzed the EST datasets, and drafted the manuscript. PB assembled and PB, JS, and AT annotated the EST datasets. CFM helped in the field and in optimization of the RNA extraction protocol. DM participated in the comparative analysis. CV carried out parts of the molecular evolution analysis. All authors read, edited, and approved the final manuscript. Cass KB8 culture originally isolated by Robert Kinzie III, Univ. of Hawaii."} +{"text": "Polymicrobial diseases involve multiple infectious agents and are referred to as complex, complicated, mixed, dual, secondary, synergistic, concurrent, polymicrobial, coinfections. This new book, a collection of 21 chapters written by a variety of authors, reviews mixed infections in animals and humans. The chapters are gathered into sections on polyviral diseases, polybacterial diseases, viral and bacterial infections, fungal infections, infections resulting from microbe-induced immunosuppression, and a concluding perspective. Polymicrobial diseases described include abscesses, AIDS-related opportunistic infections, conjunctivitis, gastroenteritis, hepatitis, multiple sclerosis, otitis media, periodontal diseases, respiratory diseases, and genital infections. Approximately two-thirds of the chapters deal with human diseases; the others discuss infections in cattle, goats, and pigs.Human herpesvirus-6, human T-lymphotropic virus type 1, measles viruses, JC virus, Epstein-Barr virus, and herpes simplex virus-1. The chapter on mixed mycotic infections adequately discusses how fungi interact by mechanisms such as commensalism, opportunism, mixed colonization, co-isolation, and dual and polymicrobial infection.The chapters are generally well written with a focus on microbiology, pathogenesis, and to a lesser degree, treatment. The chapters on abscesses, multiple sclerosis, and mixed mycotic infections are especially informative. The chapter on abscesses provides a comprehensive review of the microbiology processes involved, the role of anaerobes in mixed infections, and animal models. The section on viruses and multiple sclerosis is provocative in its proposal that several viruses might coexist and interact to promote multiple sclerosis and other neurologic diseases. The list of candidate etiologic agents includes Growing two or more microbes in the laboratory in a clinical situation does not prove that a polymicrobial infection is the cause of the disease. The editors and authors do not provide a framework similar to that of Robert Koch or Bradford Hill, which one can use to decipher the role(s) of each candidate agent in a polymicrobial infection. An limited discussion is provided on the role of noninfectious factors, such as genetics of the host, retained \u201chardware\u201d, alcohol in hepatitis, or tobacco use in respiratory diseases. How each of the chapters was selected for inclusion and what other topics were considered is not clear.The reference lists are one of the book\u2019s strengths but also a weakness. The lists are extensive, occupying about 30% of the book\u2019s pages. Prioritizing the outside readings on each topic would have been useful. Several of the chapters might have been combined, such as the two on periodontal diseases, those on retroviruses, and those on respiratory diseases in humans, cattle, and pigs. In the next edition, the authors might explore the polymicrobial etiology of Reye syndrome, autoimmune disorders, atherosclerosis, and cancers, such as Kaposi sarcoma, hepatocellular sarcoma, and cervical cancer. I recommend the book to those who think beyond the \u201csingle agent, single disease\u201d framework and imagine multifactorial causes for those diseases currently listed as \u201cetiology unknown.\u201d"} +{"text": "Leishmania, named in 1901 for British Army doctor William Leishman, who developed a stain to detect the agent. It is transmitted by the bite of certain species of sand fly, including the genus Lutzomyia in the New World and Phlebotomus in the Old World. Disease caused by protozoan parasites of the genus Leishmania donovani, was also named for physician Charles Donovan, who discovered the agent in India in 1903. An estimated 500,000 cases occur each year; India has the greatest number, followed by Bangladesh, Brazil, Nepal, and Sudan.Leishmaniasis has 2 major forms: cutaneous, characterized by skin sores, and visceral, which affects internal organs and is characterized by high fever, substantial weight loss, swelling of the spleen and liver, and anemia. If untreated, the disease is universally fatal within 2 years. Visceral leishmaniasis is also called kala-azar, a Hindi term meaning \u201cblack fever.\u201d The causal agent,"} +{"text": "Early germwarfare. The deadhurled this way turn like wheelsin the sky. Look: there goesLarry the Shoemaker, barefoot, over the wall, and Mary Sausage Stuffer, see how she flies, and the Hatter twins, both at once, soar over the parapet, little Tommy\u2019s elbow bent as if in a salute, and his sister, Mathilde, she follows him, arms outstretched, through the air, just as she did on earth."} +{"text": "The first three authors, Joshua E. Drumm, Kaixia Mi, and Patrick Bilder, should be noted as contributing equally to this work."} +{"text": "Global Burden of Disease Health Financing Collaborator Network. Future and potential spending on health 2015\u201340: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries. Lancet 389: 2005\u2013302017; \u2014The collaborators for this Article also include Lalit Dandona , Rakhi Dandona , and G Anil Kumar . These corrections have been made to the online version as of May 18, 2017, and the printed Article is correct."} +{"text": "It is often wondered as to what part of all the research performed around the globe actually leaves the lab and reaches the real people and betters their lives. In case of Professor David W. Denning\u2019s research, a large part does. As a prominent international face in the field of medical mycology, he translates his research into clinical applications and takes medical problems back to his lab, in order to develop potential solutions.He is a professor of Infectious Diseases in Global Health and a consultant in infectious diseases and medical mycology, Wythenshawe Hospital and University of Manchester. He is also the founding president of the Global Action Fund for Fungal Infections (GAFFI) and the leader of Leading International Fungal Education (LIFE). He supervises a strong research group funded by grants from the UK, USA, and Europe, as well as multiple pharmaceutical companies, with research grant income of more than 22 million pounds to Manchester University, since 1990.Aspergillus fumigatus genome . He is the Director of UK\u2019s National Aspergillosis Centre, the world\u2019s only such center based at Wythenshawe Hospital in Manchester. He has a continuing interest in the treatment of invasive aspergillosis and has been closely involved in the conduct and analysis of clinical trials of itraconazole, voriconazole, Amphotec (Amphocil), caspofungin, and micafungin. He maintains an active research program in many areas of antifungal therapy, genomics of Aspergillus, and antifungal resistance and has significant experience in both the preclinical and clinical evaluations of novel agents. He also works as a practicing physician at Wythenshawe Hospital with expertise in fungal infections, particularly aspergillosis and antifungal resistance, mainly in the immunocompromised patients.David Denning graduated from Guy\u2019s Hospital in London in 1980 and was trained in London and Glasgow in internal medicine and infectious diseases, gaining additional experience in pediatrics, hematology, gastroenterology, and immunology. He, then, undertook research training at the MRC Clinical Research Centre, Harrow, UK (1985-87), followed by a three-year fellowship in diagnostic microbiology and infectious diseases with Professor David Stevens at Stanford University, Santa Clara Valley Medical Center (1987-1990). He was granted a personal chair by the Manchester University in 2005. He coordinated the international consortium sequencing the Professor David Denning is the founder and the editor of the Aspergillus Website (with over 1 million pages read per month). His brilliant multifaceted contributions has entered him into several \u201cWho\u2019s Who\u201d listings, including in the world (since 1996/7), in healthcare (since 1997), and in science and technology (since 2005). As a prominent internationally recognized scientist, he is asked to chair several international conferences, around the globe, including but not limited to \u201cAdvances against Aspergillosis\u201d, \u201cTrends in Invasive Fungal Infection\u201d, and \u201cAspergillus Genetics and Genomes Focus Meeting\u201d.Aspergillus genomics, and the burden of fungal infections globally and in different countries.Professor Denning\u2019s main clinical interests include fungal diseases, immunocompromised patients, and complex hospital infection problems. As a translational researcher, his research interests thus focus on antifungal susceptibility testing and resistance, pathogenesis of invasive aspergillosis, clinical studies of antifungal agents, Unlike most researchers who remain confined to the boundaries of their research laboratories, David Denning has founded and promoted a number of successful businesses, making the newly developed drugs accessible to the market. In 1998, he originally founded the F2G Ltd. , and continues to serve as a clinical advisor. Later on, in 2006 he founded Myconostica Ltd. (molecular diagnostic tests for fungi) and served as its chief medical officer until 2011, when it was acquired by Lab21. He has also served and/or continues to serve as an expert consultant to multiple pharmaceutical companies with regard to antifungal drug discovery, including Merck, Pfizer, Schering-Plough, Astellas Pharma, SCYNEXIS, Cidara Theraputics, Biosergen, Pulmatrix, and Pulmocide.As a pioneer in his field, he remains a long-standing member of the Infectious Diseases Society of America Aspergillosis Guidelines Group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines Group, and the British Society for Medical Mycology Standards of Care Committee. In October of 2017, he received the prestigious award of Eduard Drouhet Medal from the European Confederation of Medical Mycology (ECMM).Professor David Denning\u2019s outstanding publications mount to more than 500 papers, books, book chapters and lectures worldwide, which have attracted over 50,000 citations. Some of these publications have reported the results of his successfully lead major international collaborative projects in highly distinguished journals such as Nature, the New England Journal of Medicine, and the Lancet.Selected recent publications:How to bolster a sparse antifungal pipeline. Science 2015; 347:1414-6.- Denning DW, Bromley MJ. Chronic pulmonary aspergillosis\u2013Rationale and clinical guidelines for diagnosis and management. Eur Resp J 2016; 47: 45-68.- Denning DW, Cadranel J, Beigelman-Aubry C, Ader, F, Chakrabarti A, Blot S, Ullman A, Dimopoulos G, Lange C, European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. How the UNAIDS target of reducing annual AIDS deaths below 500,000 by 2020 can be achieved. Phil Trans Roy Soc B 2017; 371: 20150468.- Denning DW."} +{"text": "There are errors in the author affiliations. Affiliation #2 incorrectly appears as affiliation #3 and #6. The correct affiliations are as follows:1, Swetha Manohar2, Andrew L. Thorne-Lyman2,3, K. C. Angela2, Binod Shrestha4, Rolf D. Klemm2,5, Keith P. West2Priyanka Agrawal1 International Injury Research Unit, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 2 Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 3 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America, 4 PoSHAN Study Team, Johns Hopkins University, Kathmandu, Nepal, 5 Helen Keller International, New York, New York, United States of America.There is a typographical error in the \u201cSetting\u201d subsection of the Abstract. The correct sentence is: 21 wards in seven Village Development Committees across the Tarai of Nepal in 2015.References 1 and 2 are incorrectly placed within the second sentence of the first paragraph of the Introduction. The second sentence and references 1 and 2 should appear as: Reliable prevalence estimates, with consequent quality of life and economic burdens, of untreated dental diseases, remain virtually absent to date for lack of technical capabilities in resource poor settings. .Reference 6 is incorrectly placed within the second sentence of the second paragraph of the Introduction. The correct sentence is: Commonly dental disease prevalence measures and indices such as the World Health Organization\u2019s (WHO) recommended \u201cdecayed, missing, filled teeth\u201d index (DMFT), the Oral Hygiene Index\u2014Simplified (OHI-S), and the Community Periodontal Index for Treatment Needs (CPITN) continue to remain under the sole purview of dental health scientists, clinicians and technical specialists, although structured questionnaires have occasionally been used to gather information on dental decay and pain by trained dentists in school and village settings. , 2, 6\u20138.A full stop is missing at the end of the fourth sentence in the second paragraph of the Introduction. The correct sentence is: Specifically, while generating estimates of the burdens of most severe oral diseases, the GBD fails to capture antecedent conditions to severe periodontitis such as early tooth decay or poor oral hygiene practices that precede clinical disease [5]."} +{"text": "To inform public health policy and research, we analyzed the patterns of life lost to cancers and evaluated the cancer burden in China. Based on the published Chinese Cancer Registry Annual Report and related literature in 2013, we calculated the cancer-related mortality and potential years of life lost (PYLL) by age, sex, districts , to describe the patterns of life lost to cancers. The high death-risk cancers in China were lung, liver, stomach, esophageal, colorectal, breast, pancreatic, brain and nervous system, and ovarian cancers, and leukemia. Liver and esophageal cancers were more prominent among males, while breast and colorectal cancers were more prevalent among females. The most obvious differences of mortality between urban and rural areas were found in liver, esophageal, and colorectal cancers. Cancer-related mortality increased significantly after the age of 30 years, and peaking at 70\u201379 years. The PYLL rate of cancer in urban areas was higher than that in rural areas (21.49 vs. 19.20/1000), and significant regional and gender differences of PYLL ranks can be observed. For people aged over 60 years, cancer PYLL mainly came from lung, stomach, and esophageal cancers; for middle-aged people, it was mainly induced by liver, colorectal, and female reproductive systems\u2019 cancers; and for those under 30 years, life lost to cancer was mainly caused by leukemia and brain, nervous system cancers. Moreover, disparities in age distribution of PYLL from different regions and sexes can be found. In short, three categories of people, including those in urban areas, males and people over 60 years, were suffering from more serious cancer deaths and life lost. These variations pose considerable challenges for the Chinese health care system, and comprehensive measures are required for cancer prevention and treatment. According to the data released by the International Agency for Research on Cancer (IARC), about 9.6 million deaths occurred from cancer worldwide, in 2018 ,4. AlthoThe population of China surpassed nearly 1.3 billion, accounting for about one fifth of the world\u2019s total population, a large population base whose disease epidemics, distribution and burden will have a significant impact on the world. Furthermore, obvious differences existed in regional characteristics, for example between urban and rural areas, especially in terms of factors such as culture, economy, and medical services . BecauseIn the present study, using the latest updated and published data from the National Cancer Center (NCC) of China, we aimed to describe the pattern of life lost to cancer and evaluate the cancer burden of China by calculating a crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), PYLL rate (PYLLR), and standardized PYLL rate (SPYLLR). Furthermore, to define the age of high cancer burden, age distribution charts were developed. Therefore, the combination of total death and premature death will provide a comprehensive description of the life lost caused by cancer. These findings could provide evidence for developing policies for cancer prevention and control in China, as well as act as a reference for future cancer research.Cancer-related mortality by gender, age, and districts , and population data for 2013 were derived from the published \u201cChinese Cancer Registry Annual Report, 2016\u201d and the paper \u201cReport of Cancer Incidence and Mortality in China, 2013\u201d . The annThe National Cancer Center, based on the requirements of the Chinese Cancer Registration Manual and the According to the international classification of diseases (ICD-10) , the CMRPYLLThis is an analysis index considering the age of death and the detriment of disease to human beings. It can measure the extent of harm from a death cause to a certain age group, and is often used to evaluate the risk of a disease causing \u201cpremature death\u201d ,24. Premature death, also known as advanced death, refers to death occurring before the average life span, which is evaluated by the difference between the actual age and the life expectancy, that is, the number of years of life lost in a certain cause resulting in the loss of life expectancy. The PYLL formula is as follows: (1)PYLL=PYLLRPYLL rate, PYLL per 1000 person, it is the loss of life per 1000 person in the target population, and is available for comparison:SPYLLRIf the population composition is different, the standardized PYLL rate should be calculated before comparison: In the formula (1)\u2013(3):L is the life expectancy based on the Sixth National Population Census of China in 2010 ,27, whici is the median of age group i: 0.5 for 0-group, 2.5 for 1\u20134 group, 7 for 5\u20139 group, 12 for 10\u201314 group, 17 for 15\u201319 group, 22 for 20\u201324 group, 27 for 25\u201329 group, 32 for 30\u201334 group, 37 for 35\u201339 group, 42 for 40\u201344 group, 47 for 45\u201349 group, 52 for 50\u201354 group, 57 for 55\u201359 group, 62 for 60\u201364 group, 67 for 65\u201369 group, 72 for 70\u201374 group, 77 for 75\u201379 group, 82 for 80\u201384 group, 87 for 87\u201389 group. This age grouping method was based on the Chinese Cancer Registry Annual Report [al Report , and it i represents the number of deaths in age group i. Age grouping and the data of each group also came from the Chinese Cancer Registry Annual Report [dl Report .Correction coefficient = (Pir/Nr) \u00f7 (Pi/N): Pir/Nr is the age composition of the standard population from the Sixth National Population Census of China in 2010 ; Pi/N isi. If the difference is greater than 0, it is believed that premature death has occurred. Therefore, according to L of different regions and sexes, the age threshold of premature death based on life expectancy in this study is as follows: all the areas: 77 years (median of 75\u201379 group)for all the population, 72 (median of 70\u201374 group) for males, 77 years (median of 75\u201379 group) for females; urban areas: 82 years (median of 80\u201384 group) for all the population, 77 years (median of 75\u201379 group) for males, 82 years (median of 80\u201384 group) for females; rural areas: 72 (median of 70\u201374 group) years for all the population, 72 (median of 70\u201374 group) for males, 77 years (median of 75\u201379 group) for females.N is the total population of premature deaths. PYLL judges premature death according to the difference between L and aFinally, in order to describe the age group more concisely, we merged them according to the World Health Organization (WHO) age grouping method used to estimate cancer burden , and PYLWe ranked nationwide cancer-related mortality rates by district and sex, and then selected the top 10 as the high death-risk cancers in China. Subsequently, we conducted a detailed analysis of the life loss patterns caused by these high death-risk cancers.P = 0.05.Using Excel 2016 and SPSS 25.0 software to collate and analyze the data. The standardized mortality rate of China (SMRC) was calculated according to the standard population age composition of the national census in 2010 , and the5, including 1.406 million males and 823,000 females . The CMR for lung cancer was the highest, at 46.9/105, followed by those for liver, stomach, esophageal, colorectal, breast, pancreatic, brain and nervous system, and ovarian cancers, and leukemia. Similarly, for males and females, the highest CMR was for lung cancer, at 62.9/105 and 30.5/105, respectively. It was followed by those for liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic cancer, brain and nervous system cancer, leukemia, lymphoma, and prostate cancer in males. In females, the CMR for lung cancer was followed by those for stomach, liver, colorectal, breast, esophageal, pancreatic, cervical, brain and nervous system cancers, and leukemia . The CMR for lung cancer was the highest, at 50.5/105, followed by those for liver cancer, stomach cancer, colorectal cancer, breast cancer, esophageal cancer, pancreatic cancer, prostate cancer, leukemia, and cervical cancer. Similarly, for both sexes, the highest CMR was for lung cancer . In males, it was followed by those for liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic cancer, brain and nervous system cancer, leukemia, lymphoma, and prostate cancer. In females, the CMR for lung cancer was followed by those for stomach, liver, colorectal, breast, esophageal, pancreatic, cervical, and brain and nervous system cancers, and leukemia . The CMR for lung cancer was the highest, at 43.5/105, followed by those for stomach, liver, esophageal, colorectal, breast, pancreatic, brain and nervous system, and ovarian cancers, and leukemia. Additionally, for both males and females, the highest CMR was for lung cancer, at 58.1/105 and 28.1/105, respectively. It was followed by those for liver cancer, stomach cancer, esophageal cancer, colorectal cancer, pancreatic cancer, brain and nervous system cancer, leukemia, lymphoma, and prostate cancer in males. In females, the CMR for lung cancer was followed by those for stomach, liver, esophageal, colorectal, breast, pancreatic, cervical, and brain and nervous system cancers, and leukemia but lower PYLL (fifth rank) for colorectal cancer. However, the circumstances of breast cancer was the opposite . This phenomenon can be explained by another finding of the present study, that deaths caused by colorectal cancer were common among individuals aged 80+ years, while those caused by breast cancer mainly occurred among individuals aged 45\u201359 years. As the latter were younger, they exhibited a higher PYLL. It can be seen that female breast cancer was a kind of \u201cyounger cancer\u201d, and the peak age of death of Chinese female breast cancer was younger than that of other countries. For example, American female breast cancer patients died mostly between 55 and 64 years of age , while KAdditionally, the overall premature death of cancer in urban areas was more serious than that in rural areas, especially lung cancer. However, the conclusions of PYLL about urban and rural reported by Zhang et al. was incoWorldwide, lung cancer was reported as the leading cause of cancer deaths among males and the second leading cause among females . In the With the development of the social economy, large changes in lifestyle, and rapid aging of the population, mortality related to colorectal cancer in China was reported to be on the rise, especially in urban areas . In GlobThe death and burden related to esophageal cancer in China also showed significant regional and gender differences. The PYLL for esophageal cancer was higher among males, while it did not appear in the top five ranks among females. This finding may be explained by the fact that males are more likely to have several unhealthy habits such as smoking and alcohol abuse. In the Chinese population, about half of esophageal-cancer-related deaths were attributable to smoking, alcohol drinking, and low vegetable and fruit intake, with smoking and alcohol drinking being responsible for about 30% of the mortality related to esophageal cancer . TherefoAlthough the present study only described the current situation, the above description of existing and emerging patterns related to cancer in China calls for the development of varied interventions to reduce the disease burden. Such efforts should include balanced investment in awareness and educational efforts targeting the general population and primary care practitioners, particularly focusing on the primary prevention of hepatitis B and human papilloma virus infections, tobacco control measures, and promotion of physical activity and healthy diet. In sum, it was meaningful to understand the patterns of cancer-related death and life lost, in that this information could be used to develop cancer prevention and treatment measures for different age groups, genders, and regions. We conclude that lung, liver, stomach, breast and colorectal cancers were the main cancers causing premature death in China. These cancers were also at the forefront of the PYLL ranking in urban and rural areas, but for rural residents, besides these cancers, the impact of esophageal cancer could not be ignored. For males and females, in addition to paying close attention to lung cancer, separate attention should be given to liver and breast cancers. People aged over 60 years were a concentrated age group with a large number of cancers causing life lost. Based on these findings, the relevant departments should assign importance to high-risk populations and cancers, to effectively reduce the burden of cancer and improve quality of life."} +{"text": "As an arts-based, creative storytelling program for persons living with Alzheimer\u2019s Disease and related dementias (ADRD), TimeSlips involves a facilitator showing a picture to participants, who then exercise their imagination to create a story. The program has shown to benefit participants\u2019 well-being, possibly because of the opportunity to express themselves. Although they may reflect participants\u2019 values and identities, the content of such stories had not been the focus of investigation. The aim of this study is, therefore, to identify major themes of such stories through a qualitative content analysis. We implemented a creative storytelling program at Silverado Onion Creek Memory Care Community in Austin, and offered 6 weekly sessions with 4 small groups of residents. A total of 26 residents participated in the study, creating 24 collective stories in total. Three researchers first open-coded these stories and then met to reach consensus concerning the themes that emerged. Ten themes were identified: family values, generativity, religious reference, reference to love, reference to home, cultural norms, uncertainty and worries, positivity, negativity, and dissonance and disagreements. The first 6 themes represent the values, beliefs, and norms of the participants, with the remaining 4 reflecting their personal identities, personalities, and experiences. The findings suggest that they continue to value families and religion, care about others, and make judgements about people, things, and circumstances that they face. Researchers, practitioners, and care partners can benefit from \u201clistening to\u201d creative storytellers more closely to learn about their opinions, expectations, and preferences."} +{"text": "The growing field of technology and aging or gerontechnology has largely been considered from a health perspective on technological intervention to ameliorate conditions of isolation, disconnection, inactivity, and loneliness, as well as provide efficient alert systems, transportation coordination, and emergency services. Contesting the image of a \u2018digital divide\u2019 separating younger from older generations, the recreational industry has also produced a seniors market of technological games, toys, apps, exercises, and social media. The four papers in this symposium, however, are individual critical reflections by a group of social scientists who visited the Consumer Electronics Show (CES) in January 2019 (Las Vegas) as part of an ethnographic project about the politics of the technical turn in gerontological studies. In particular, the authors gathered evidence from the CES to support their interests in four trends: a) The collecting, aggregating, and sharing of personal data by home surveillance, artificial intelligence monitoring, and self-tracking systems for commercial, insurance and work-place purposes, b) The popularization of healthy lifestyles based on technical and exclusionary models of \u2018smart\u2019, \u2018fit\u2019, and \u2018optimal\u2019 standards, c) The technical rhetoric that infuses designs for efficiency, speed, and convenience with anti-aging and ageist ideologies, d) The challenges to older people to manage their lives against the health risks, interventions, and expectations posed by technology-driven austerity programs. The papers have in common their creative interpretations of CES materials and shared concern about the many older groups whose insufficient access, skill, and resources will deny them participation in the technological imaginary of aging futures."} +{"text": "All too often the quality and rigor of topic investigations is inaccurately conveyed to information professionals, resulting in a mischaracterization of the research, which, if left unchecked and published, may in turn mislead potential readers. Accurately understanding and categorizing the types of topic investigation searches that are requested of information professionals is critical to both meeting requestors\u2019 needs and reflecting their intended methodological approaches. Information professionals\u2019 expertise can be an invaluable resource to guide users through the investigative and publication process. Systematic reviews have long played an important role in the evidence hierarchy , yet thelabeled as \u201csystematic reviews\u201d that potentially do not meet the rigorous criteria of systematic reviews [With the ongoing expansion of the body of systematic reviews in the literature comes the expansion of articles reviews . Such mitrue systematic reviews continues to elude the research community, despite guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [why we continue to see the term \u201csystematic review\u201d improperly applied in published studies to describe less rigorous types of information inquiry [A deep and clear-cut understanding of the nature of tatement , Agency tatement , Cochrantatement , and Nattatement . Given t inquiry , despiteUnfortunately, the root cause can likely be traced to a lack of accurate understanding of the aims and goals of how the search inquiry results will ultimately be used. Physicians, researchers, and even information professionals tend to deem studies or design methods loosely resembling those used in the systematic review process as actual systematic reviews, despite incompleteness and lack of adherence to all the parameters necessary to be a true systematic review. Although these errors are often unintentional, the continued volume of erroneously labeled information search inquiries devalues the term \u201csystematic review,\u201d which is intended to denote independent, unbiased, and objective assessment of evidence and includes rigorous evaluation of the strength of study results and analysis of study bias, painstakingly described for methodological transparency and reproducibility , 9.systematic review and adhere to all criteria established by the aforementioned authoritative guides? Or is the user seeking what CKM has coined a \u201csystematic-like\u201d review, a review that incorporates some features of a systematic review without adhering to all the required components [rapid review, done for topics that are still emerging and for which little has been published [comprehensive literature review or a patient-specific precision investigation with or without content filtering of the information retrieved? It is very telling how much confusion can be eliminated when this simple process is followed; thus showing the need for us, in our role as educators and information providers, to become better versed in the labeling of searches as we inquire and collect data on the type of information need our users are seeking.Staff at the Center for Knowledge Management (CKM) are too often erroneously asked for assistance in conducting \u201csystematic reviews.\u201d As a result, we have armed ourselves with an approach to guide the requester to the type of searching and information retrieval support that is most suited to their needs, while also continuing to educate our professionals on the proper use and labeling of the different types of searches. So, we ask: Does the user really want to conduct a true mponents ? Or do tublished \u201313? Or iPer guidance from multiple organizations, systematic reviews must meet specific requirements \u20137, 9. SyOn the other hand, \u201csystematic-like\u201d reviews allow investigators flexibility to select from the standard list of systematic review components and achieve a much shorter turnaround time than that required of true systematic reviews. For instance, a small group of physicians may believe they want to conduct a systematic review but may not be interested in devising a protocol or have the time to conduct risk of bias assessments of selected studies. Lacking such elements precludes the resulting manuscript from being categorized as a true systematic review; however, the application of parts of the systematic review methodology should be recognized.We are not alone in this attempt to categorize studies falling short of the gold standard for systematic reviews. Another form of categorization that draws from systematic reviews is the \u201crapid review,\u201d which has arisen in the last ten years or so to more accurately convey the idea that a quickly performed inquiry is somewhat rigorous without being a full-fledged systematic review . These \u201cAnother area where all too frequently users misappropriate the term \u201csystematic review\u201d is in lieu of a comprehensive literature search. The investigator knows that they want a very thorough expert search and review of the biomedical literature, but they understand \u201csystematic\u201d to mean \u201cplanned, organized, and methodical.\u201d Comprehensive literature searches that CKM conducts involve an extensive expert review of the relevant published and grey literature; use of more than one database, with or without filtering and synthesis of the resulting articles; and an unbiased presentation of the literature around a given topic . These cThe inherent value of these types of reviews stems from their comprehensiveness. For instance, researchers can take solace in an information professional saying, \u201cThere is no answer,\u201d knowing that the topic has been exhaustively explored. Clinicians who may be seeking answers to clinical questions, without wanting to disclose patient-specific information, can rest assured knowing that all the relevant evidence has been considered and the most rigorous studies are being selected. Answering these questions still requires the same level of careful \u201csystematic searching\u201d without necessitating a full-fledged systematic review. These searches address questions such as what the literature says about treating a certain condition, whether a research question has been sufficiently investigated by others, what a standard work-up for a patient presenting to a particular service in the clinical environment is, or whether a clinician has taken the best course of action. If the 2,400 most recent complex questions in our internal database are any indication, this type of search can take an average of 8 hours to complete.Patient-specific precision investigation allows the highest level of personalization in searching. These are questions pertaining to a single patient that come directly from clinicians and researchers and may be submitted through the medical record, morning reports, or patient conferences such as tumor boards \u201320. ContFixing the cycle of mis-categorization requires more than educating a set of researchers and physicians on the differences in topic investigations: it involves a concerted effort on the part of information professionals to educate ourselves on the key differences in the types of information inquiry asked of us and then actively working to stop perpetuating the misuse of terms by acquiescing to pressure from collaborators. Information professionals who have been involved in the development of true systematic reviews can attest that searching the biomedical literature in a systematic fashion only scratches the surface of what is entailed in genuine systematic reviews, which to be complete also require the active collaboration of content experts for data evaluation and final construct. The genuine impact of all other types of searches remains unquestioned when their role and appropriateness of use is clearly understood and properly applied. Teaching users how to properly label their requests based on their needs will greatly improve the significance of our role as coaches, educators, and information providers in the communities we are charged to inform.Zachary E. Fox, MSIS, Zachary.e.fox@vumc.org, Associate Director for Information Services, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNAnnette M. Williams, MLS, annette.williams@vumc.org, Senior Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNMallory N. Blasingame, MA, mallory.blasingame@vumc.org, Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNTaneya Y. Koonce, MSLS, MPH, taneya.koonce@vumc.org, Associate Director for Research, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNSheila V. Kusnoor, PhD, sheila.v.kusnoor@vumc.org, Senior Research Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNJing Su, MD, MS, jing.su@vumc.org, Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNPatricia Lee, MLS, patty.lee@vumc.org, Senior Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNMarcia I. Epelbaum, MA, marcia.epelbaum@vumc.org, Senior Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNHelen M. Naylor, MS, helen.naylor@vumc.org, Senior Research Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNSpencer J. DesAutels, MLIS, spencer.desautels@vumc.org, Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNElizabeth T. Frakes, MSIS, elizabeth.frakes@vumc.org, Information Scientist, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TNNunzia Bettinsoli Giuse, MD, MLS, FACMI, FMLA, nunzia.giuse@vanderbilt.edu, Vice President for Knowledge Management; Professor, Department of Biomedical Informatics; Professor, Department of Medicine; and Director, Center for Knowledge Management, Strategy and Innovation, Vanderbilt University Medical Center, Nashville, TN"} +{"text": "Bernadette Rosati was not included as an author in the published article. The corrected Author Contributions Statement appears below:\u201cThe study concept and design was developed by SH, MA, JL, and T\u0160-T, and the experiments were executed by SH, MA, SC, MS, BR, ML, and T\u0160-T. Data analysis was performed by SH, MA, SC, MS, BR, ML, TB, and T\u0160-T. All authors were involved in several rounds of critically reviewing the manuscript.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors of \u201cPartnering With Mommy Bloggers to Disseminate Breast Cancer Risk Information: Social Media Intervention\u201d :e12441) made an error when listing the affiliation of author Carla Fisher.Her affiliation was previously \u201cCollege of Health and Human Performance, University of Florida, Gainesville, FL, United States\u201d and has now been changed to \u201cUniversity of Florida, UF Health Cancer Center, Gainesville, FL, United States\u201d.The correction will appear in the online version of the paper on the JMIR website on June 17, 2019, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article also has been resubmitted to those repositories."} +{"text": "In the published article, there was an error in the affiliation for Zoran Grgantov. Instead of affiliation 6, \u201cFaculty of Psychology, eCampus University, Novedrate, Italy,\u201d the correct affiliation for Zoran Grgantov should be affiliation 7, \u201cFaculty of Kinesiology, University of Split, Split, Croatia\u201d.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Almost every region of Pakistan is stacked with a large number of medicinal plants. Due to high cost and unavailability of allopathic medicines for the neurological diseases, especially in rural areas, traditional healers prescribe phytotherapy for various neurological diseases like epilepsy, depression, anxiety, insomnia, Alzheimer, and migraine. Such treatments are considered to be most effective by the native people. The data was collected from articles published on medicinal plants of various districts of Pakistan, using article search engines like Medline, Pubmed, Web of Science, Science Direct, and Google Scholar. Also, information regarding various neurological uses and mode of applications of medicinal plants was obtained from traditional healers, folk medicine users, and local elderly people having knowledge of medicinal plants. A total of 54 families were found to be used in various neurological diseases, of which the highest use was of Solanaceae (22.22%), Asteraceae (12.96%), Lamiaceae, Papaveraceae, and Poaceae, 9% each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5% each. According to districts, 15% of plants that were effective in neurological affections were found in Bahawalpur, 11% in Swat, 8% in Muzaffarabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each. According to the plant's habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33% trees, 11.65% shrubs, and 4.85% climbers. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, and flowers were found to be used 32.03%, 24.27%, 20.38%, 16.50%, 13.59%, and 11.65%, respectively. According to disease's types, 45.63% were found to be effective in insomnia, 31.06% in epilepsy 12.62% in depression, 6.80% in anxiety, 7.77% in hysteria, and 5.88% in migraine. Taking into consideration this useful knowledge on medicinal properties of the plants for curing neurologic diseases, it is believed that research in areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding value to the very rich natural resources of Pakistan. This study will help all the researchers from diverse backgrounds working on plants based medicine for neurological diseases. Globally, neurological diseases are among the major contributors to mortality and morbidity, particularly in developing nations. The well-known manifestations of neurological diseases include mood swing, restlessness, hopelessness, poor coordination, seizures, impaired cognition, paralysis, distress of sensation, muscle weakness, pain, and confusion . There aAbout 45 million people of the world, above 18 years of age, suffer from schizophrenia at some stage of their lives, 340 million are affected by depression, and both these diseases are accountable for 60 % of all suicides, while Alzheimer and epilepsy affect about 11 and 45 million people, respectively, around the world accounting for 1% of the total disease burden in the world [In Pakistan, about 10 % people suffer from mental diseases, representing a foggy picture with 2% prevalence of' epilepsy, 5% depression, 1% Alzheimer, and 1.5% schizophrenia as shownMedicinal plants have been used from the very beginning in health care systems. Studies have been carried out globally to verify their efficacy and some of the findings have led to the production of plant-based medicines. Due to limited access to modern medicine, the local population uses medicinal plants to treat most diseases , 7. ReceHerbs may provide a source of new compounds including many drugs that are derived from plant sources. For several neurological diseases, modern medicine offers symptomatic treatment that is often expensive and associated with side effects. Indian system of medicine has traditionally been used in several neurological conditions. The accessibility, cost effectiveness, and lower incidence of side effects of plant products offer considerable advantages . Bacopa monnieri, Cannabis sativa, Solanum nigrum, Withania somnifera, Papaver somniferum, Zizyphus jujube, Tribulus terrestris, and Verbena officinalis showed different neuropharmacological activities. These agents can be used alone or as adjuncts to standard drugs, used for various neurological diseases like depression, epilepsy, schizophrenia, Alzheimer, Parkinson, hysteria, melancholia, and dementia, for increasing their efficacy and decreasing side effects.Various plant extracts have been screened and investigated for their potential neuropharmacological activities in different experimental models of animals comprising mice and rats. Herbal extracts and natural products includingIn developing countries, plant-based medicines are being used by 75-80% of population . The knoIn Pakistan, folk medicines have more use in rural and less developed areas for the treatment of various diseases because of easy access, cost effectiveness, less side effects, and unavailability of allopathic therapeutic agents . This tyFirst the articles published on the medicinal plants of various districts of Pakistan were searched in online research database, i.e., Medline, PubMed, Web of Science, Science Direct, and Google Scholar, by using special key words \u201cmedicinal plants\u201d, herbal plants, neurological diseases, specific districts names, antialzheimer, antiparkinson, antidepression, sedative, anxiolytic, antiepileptics, epidemiology, and prevalence, from January to March 2018, and downloaded. These entire articles were then viewed and the data of medicinal plants, which have neurological effects, were collected and tabulated in . We haveA total of 54 families were found to be useful in various neurological diseases, of which the highest use was of Solanaceae (22.22 %), Asteraceae (12.96 %), Lamiaceae, Papaveraceae, and Poaceae, 9 % each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5 % each . As per This district-wise plant distribution will help the researchers, who are willing to research in neuropharmacological area, to easily collect the target plants from the regions to which the plants belong. According to the plant's habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33 % trees, 11.65% shrubs, and 4.85% climbers .The habit of plants shows that herbs are most important according to neuropharmacological point of view which is another benefit for researchers working in neuropharmacological area to concentrate on herbs more while selecting neurological active plants. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, flowers, and other parts were found to be used 32.03 %, 24.27 %, 20.38 %, 16.50 %, 13.59 %, 11.65 %, and 15.53 %, respectively . As someAccording to disease's types, 45.63 % were found to be of therapeutic value in insomnia, epilepsy (31.06%), depression (12.62%), anxiety (6.80%), hysteria (7.77%), and migraine (5.88%) and 20.38 % in other neurological diseases . As someThe pharmacological activities of plants are due to the presence of various phytochemicals mainly alkaloids, flavonoids, tannins, saponins, resins, glycosides, terpenoids, phenols, sterols, essential oils, vitamins, and nutrients. Some of these are effective in the treatment of neurological diseases; some are useful for cardiovascular, respiratory, and gastrointestinal diseases while others have chemotherapeutic and antibacterial effects. Some of the important phytochemicals of the plants includinBacopa monnieri plant is reported for anxiety, depressant, epilepsy, and Parkinsonism and contains alkaloids , saponins (hersaponin and monnierin), flavonoids (luteolin and apigenin), and sterols like b-sitosterol and stigma-sterol. These constituents are already reported for such neuropharmacological properties and so might be responsible for said activities of this plant [is plant \u201336.Cannabis sativa L. has been reported for the treatment of depression, anxiety, convulsion, Alzheimer, dementia, and insomnia and its constituents responsible for these properties are cannabigerol, tetrahydrocannabinol, and cannabidiol [nabidiol \u201341.Verbena officinalis Linn. has been reported as anxiolytic, antidepressant, anticonvulsant, and sedative and its constituents responsible for these activities are verbenin, verbenalin, hastatoside, kaempferol, luteolin, verbascoside, aucubin, and apigenin [apigenin \u201344.Withania somnifera has been shown to have anxiolytic, antidepressant, anticonvulsant, and anti-Parkinson effects, mainly due to the presence of withanolides, sitoindosides VII\u2013X, and withaferin-A [aferin-A \u201348.These chemical constituents of plants act on the central nervous system through various mechanisms including regulation of neurotransmitters like adrenergic, cholinergic and serotonergic activity, acting through receptor like GABA and N-methyl-D-aspartate, and ion channels like sodium, potassium, and calcium ion channels. Some of the plant-based drugs and phytochemicals which either are approved or are under clinical trials for the treatment of neurological diseases, mechanism of actions, and their current status in clinical trials are given in .Taking into consideration this useful knowledge on the medicinal properties of plants for curing neurologic diseases, it is believed that the research in the areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding importance to the very rich natural resources of Pakistan. Various phytochemicals from the above medicinal plants can be further researched under clinical trials and better drugs for treatment of neurological diseases can be obtained with outstanding results and lesser side effects. This study will help all the researchers, especially from Asian countries including Pakistan, China, Iran, India, Sri Lanka, and Bangladesh, working on plants based medicine for neurological diseases.The mental illnesses are one of the major problems of the world mainly in communities presenting with poor socioeconomic conditions. In Pakistan and other countries of this region, there is no accurate and up to date record of the neurological ailments. In order to find any treatment for these diseases, first realistic survey would be required to find out the exact percentage of various neurological diseases. Being an alarming psychiatric problem, Alzheimer opens a new area of research, affecting an enormous part of world population, but it is still untreatable. A lot of attempts have been conducted but still there is no such drug that can either slow or stop the process of Alzheimer disease. Allopathic medicines are available for psychological diseases including anxiety, depression, epilepsy, Parkison, and Alzheimer, but these are either not so effective or costly or have serious associated adverse effects. The world is full of natural medicinal resources, of which the main source is plant. We should invest money and go for systemic scientific investigations to perceive such drug candidates' form these plants, which are most efficacious, have minor side effects, and are cost friendly. For this purpose, this study is a gift for researchers who have interest to design and perform research based activities in the field of neuropharmacology by evaluating the unexplored medicinal plants mentioned here for their folkloric uses, determining its mechanistic pathways and identifying chemical constituents responsible for therapeutic effects."} +{"text": "The Medical Library Association (MLA) held its 118th annual meeting in Atlanta, Georgia, May 18\u201323, 2018, at the Hyatt Regency Atlanta. The meeting theme was \u201cAdapting, Transforming, Leading.\u201d Total attendance for the meeting was 1,670, with 236 participating in continuing education courses. Additional meeting content\u2014including the meeting program and various electronic presentations from the business meeting, plenary sessions, poster sessions, and program sessions\u2014can be accessed by all meeting registrants via the MLA \u201918 website.Executive Director Kevin Baliozian welcomed attendees and gave a pre-session announcement about a suicide in the hotel in a public area the night before. He discussed the steps MLA was taking to reach out to members who had been present as well as counseling services provided by the hotel. He then introduced MLA President Barbara A. Epstein AHIP, FMLA.MLA President Barbara A. Epstein, AHIP, FMLA, welcomed attendees to the 2018 annual meeting. She updated the audience on a change to the meeting format in regard to how awards would be given out over a series of sessions, rather than all at once, and encouraged everyone to attend the plenary sessions and visit with vendors throughout the meeting. President Epstein then introduced Connie K. Machado, AHIP, who welcomed attendees on behalf of the Southern Chapter.Connie K. Machado, AHIP: Good morning and welcome. The Southern Chapter and all its members extend a warm welcome to you in beautiful downtown Atlanta on behalf of MLA for this 118th annual meeting. Many of our local Southern Chapter members have worked with MLA to plan this exciting meeting and venue for all of you in attendance. We hope that you are able to adapt to our humidity and temperatures while you\u2019re here in the South.Founded in 1951, the Southern Regional Group later transformed to the Southern Chapter and has hosted three MLA meetings in this region. It has been seventeen years since the last meeting, which was held in Orlando, and we welcome you back with our warm Southern charm, great food, and hospitality. The Southern Chapter has a reputation for having fun and hosting great social events, so we hope you take some of our spirit of Southern hospitality home with you.Throughout the Southern Chapter\u2019s rich history, many of our founding librarians have served as MLA president and in other positions as leaders. Names like Eileen Cunningham, Mildred Crow Langner, and Mary Louise Marshall, as well as William (Bill) Postel, Alfred N. Brandon, Mildred Jordan, T. Mark Hodges, and a host of others. And I\u2019m sure that there will be more leaders to come in the future.Most of you have passed through Atlanta when traveling, at least at the airport. But there is much more to see and absorb here in the city\u2019s rich history. Southern Chapter members are pleased to welcome you to Atlanta, home to the Centers for Disease Control and Prevention (CDC), Coca-Cola, and CNN, and plenty of dining experiences and fun places to visit during your stay. They also have seventy-five streets with the name \u201cPeach\u201d in it, so navigate carefully. So, again, I welcome you on behalf of the Southern Chapter members and MLA.Now, please join me in welcoming these truly creative and dedicated members who have spent more than three years planning this Atlanta meeting: the 2018 National Program Committee (NPC) Cochair David A. Nolfi, AHIP; 2018 NPC Cochair Debra Berlanstein, AHIP; 2018 Local Assistance Committee Chair Sandra G. Franklin, AHIP, FMLA; and 2018 Local Assistance Committee Cochair Joe Swanson Jr. Let\u2019s give them a big hand.David A. Nolfi, AHIP: Thank you, Connie. On behalf of the MLA 2018 National Program Committee and the Local Assistance Committee, we officially welcome you to Atlanta, the first time for the MLA annual meeting. Our theme, \u201cATL: Adapting, Transforming, Leading,\u201d reflects both this vibrant city and the spirit of our membership. The rising phoenix in our logo reflects the rise of Atlanta to become the dynamic leader in commerce, health care, research, education, and entertainment that it is today.Debra Berlanstein, AHIP: As medical librarians, we too, are continually evolving and searching for innovative ways to grow, change, reimagine, and most of all, make a difference. We know you will be inspired by the programming and the many opportunities to connect and share with colleagues during your stay in this amazing city. We hope you will get out and about and explore the world outside the doors of the Hyatt Regency Atlanta.David Nolfi: Planning this meeting over the last two years gave us the privilege of working with a great group of enthusiastic librarians whose hard work, energy, and commitment made cochairing the committee a pleasure. And so I ask now, would the members of the National Program Committee as well as the MLA staff who worked on the meeting please stand to be recognized. And now I ask you to please welcome Sandra Franklin, chair of the Local Assistance Committee, and Joe Swanson Jr., cochair.Candide, by Leonard Bernstein.Joe Swanson Jr.: Welcome to Atlanta. We\u2019re so glad that you\u2019re here and we hope you have an enjoyable time. We want you to enjoy the sessions and so forth. But in the meantime, we want you to have a little fun. We know that some of you have already been out and about, but you can visit places like the botanical gardens, the Jimmy Carter Library and Museum. You\u2019ve already been around the attractions at the Centennial Olympic Park. And the Atlanta Symphony Orchestra will be performing Applause.]So, as I said, we want you to enjoy the meeting, but in your spare time and for those who are going beyond the meeting, enjoy the city. And come back to see us! We have what we call Southern hospitality here. Thank you. They\u2019re scattered hither and yon, but just thank them if they\u2019re near you.In addition to that, I\u2019d like to thank personally everyone who has worked on this committee, but especially our Local Assistance Committee. They each had their tasks, they did their tasks and just did a fantastic job, and you\u2019re seeing the results of that. So I\u2019d like all of them to stand. Please stand [and be recognized] for this 2018 meeting. , in building stronger relationships between these groups. And if you don\u2019t know what the NIH All of Us research program is, plan to be here on Wednesday morning to hear Dr. Dara Richardson-Heron.This is an initiative of MLA and the Public Library Association, and it is funded by the National Network of Libraries of Medicine (NNLM) and the NIH All of Us research program. And this unique partnership allows us to leverage the expertise of our members, of you And third, my family. We have two great daughters who married two great sons-in-law, who brought us four terrific grandchildren. And the littlest one is Hartley, who was born just last month, and she\u2019s still tiny. She\u2019s eating a lot, she\u2019s more than eight pounds now, and we expect her to grow into her hair bows very soon. [Applause.]And last but not least, my husband, Arnold. Through the years, he has been my confidante, my sounding board, my gentle critic, my press agent, my legal advisor, my best friend, and my secret sauce. I have dragged him to a few MLA meetings, and I have to say he sometimes enjoys them way more than I do. Last night, he came back from the exhibit opening with just a whole bagful of stuff that he collected and a list of people he talked to. And I think marrying him was the best decision I ever made. Thank you. If you have any questions, you\u2019re welcome to email Cujo, my dog, and he will respond to you, or you can email me or Ray, whatever you prefer. Thank you for all of your time. Why has it increased? Because of new programming, like the InSight Initiative, sponsored by the participating organizations, that allowed us to have the librarian attendees attend for free and pay for travel expenses, which is great.That number has increased by an impressive $46,000 this year, affecting 150 individuals. And lastly, after this meeting, vacation and kind of a zen in Canada on Lake Huron. And so between the graduation and that, I\u2019ve had the pleasure of being here and meeting all of you. Thank you. Now, I hope most of you know who Chef Ramsay [Gordon Ramsay of Hell\u2019s Kitchen] is, because if you don\u2019t, this won\u2019t make any sense at all. And anyway, what does that have to do with libraries, you say? Well, nothing. But it does have an analogy to what I want to say.So, I\u2019ve titled this time with you today: If Chef Ramsay was coming to your house, would you cook? So, I\u2019m in the kitchen, but I\u2019m not necessarily the expert. We, collectively, are the experts. And if Chef Ramsay was coming to my house, heck, no, I wouldn\u2019t cook, because he scares me. But I\u2019m not afraid of you, because you are all my colleagues, and I feel comfortable in saying this: In the 120th year of the association, I am proud and honored to be the first African American president of the Medical Library Association. We are changing. We are becoming a more diverse society. But our profession has not yet caught up to that. And I want to thank Elaine R. Martin, as she so beautifully articulated that yesterday in her Doe lecture, so thank you Elaine. You said everything I wanted to say and didn\u2019t have time. So, over the next year, I want you to remain calm, I want you to remain open, I want you to remain flexible, and I want you to remain positive. As we\u2019re sitting in this room here in Atlanta\u2014the home of Coke, fried foods, grits, and pie\u2014we\u2019re making history together. Thanks for taking this journey with me and helping to shape the framework for the next year and years to come. You will always be the sunshine in my life. Thank you. [Applause.]I\u2019d like to thank everyone. And please join us tonight for the Silver and Gold Networking Dinner, where we will present a few remaining awards and be entertained by our colleagues at MLA\u2019s first-ever talent show. And get a sneak-peek at next year\u2019s meeting, when the 2019 National Program Committee presents the MLA \u201919 invitation. This session is now closed. [The Silver and Gold Networking Dinner, sponsored by McGraw-Hill Education, was held on Tuesday, May 22, 2018, from 6:30 p.m.\u201310:00 p.m. The networking dinner was in a different format than in previous years and featured a talent show, which included a live band, singing, a sing-along, and poetry. The MLA \u201919 Invitation to Chicago also took place and was hosted by James Dale Prince, AHIP, chair, 2019 National Program Committee, and executive director, Southeastern/Atlantic Region, National Network of Libraries of Medicine, University of Maryland\u2013Baltimore; Mellanye J. Lackey, cochair, 2019 National Program Committee, and associate director, Education and Research, Spencer S. Eccles Health Sciences Library, University of Utah\u2013Salt Lake City; Rosie Hanneke, AHIP, chair, 2019 Local Assistance Committee, and information services and liaison librarian, Library of the Health Sciences, University of Illinois\u2013Chicago; and Debra Werner, cochair, 2019 Local Assistance Committee, and director, Library Research in Medical Education, John Crerar Library, University of Chicago, Chicago, IL. The Dental Section, recipient of the MLA Section Project of the Year Award, and the Mid-Atlantic Chapter of MLA, recipient of the Majors/MLA Chapter Project of the Year (sponsored by J.A. Majors), were recognized during the dinner.Journal of the Medical Library Association.Section programs were presented in 4 time slots: Sunday, May 20, 3:00 p.m.\u20134:25 p.m.; Monday, May 21, 10:30 a.m.\u201311:55 a.m., and 1:00 p.m.\u20132:25 p.m.; and Tuesday, May 22, 3:00 p.m.\u20134:25 p.m. Paper abstracts that were scheduled to be presented are available on the MLA \u201918 website. The final version of the abstracts, reflecting only those presented at the meeting, is included as an online-only Journal of the Medical Library Association.Poster sessions were presented in 4 time slots: Sunday, May 20, 2:00 p.m.\u20132:55 p.m.; Monday, May 21, 2:30 p.m.\u20133:25 p.m.; and Tuesday, May 22, 1:00 p.m.\u20131:55 p.m., and 2:00 p.m.\u20132:55 p.m. Poster abstracts that were scheduled to be presented are available on the MLA \u201918 meeting website. The actual posters are available online in the MLA \u201918 meeting website. The final version of the abstracts, reflecting only those posters presented at the meeting, is included as an online-only On Thursday, May 17, the MLA Board of Directors met. The MLA Board of Directors and Credentialing Committee met on Friday, May 18. On Saturday, May 19, the following groups met: 2019 National Program Committee; 2019 program planners; Chapter Council; Communities Strategic Goal Task Force; Joint Section Council/Chapter Council; National Network of Libraries of Medicine (NNLM) Steering Committee; Nominating Committee; and Section Council.JMLA Editorial Board; Leadership Curriculum Committee; Metadata 2020: Join the Discussion to Help Improve the Quality of Metadata for Research; Midcontinental Chapter Meeting and Greet #1; Outreach and Marketing SIG Business Meeting; Research and Evidence-Based Practice Curriculum Committee; Research Section Research Award Judging; Research4Life Grants Workshop Planning Session; Resource Sharing SIG Business Meeting; and Systematic Reviews SIG Business Meeting. Exhibitor meetings included: Lunch & Learn: AAAS/Science: The Blurred Line between Fact and Fiction; Medical Librarian Lunch and Learn: EBSCO Health; Cell Press & The Lancet Lunch & Learn: Best Practices in Publishing and Reproducibility; Supporting Institutional Research and Raising the Profile of the Library; and The R2 Digital Library as a Health Sciences eBook Database.On Sunday, May 20, the following groups, sections, and SIGs met: AAHSL Future Leadership Committee; AAHSL Leadership Fellows Program; AAHSL New and Developing Libraries Committee; Ad Hoc Committee to Review Core Clinical Journals; African American Medical Library Alliance SIG Business Meeting; chapter treasurers orientation meeting; Collection Development Section Business Meeting; Consumer and Patient Health Information Section (CAPHIS) Business Meeting and Executive Committee Meeting; Data SIG Business Meeting; Education Steering Committee; Educational Media and Technologies Section (EMTS) Business Meeting #1; Fellows of MLA; Health Disparities SIG Lunch; International Cooperation Section Business Meeting; Interprofessional Education SIG Business Meeting; On Monday, May 21, the following groups, sections, and SIGs met: 2020 National Program Committee; AAHSL Research Services Committee; Around the World: Global Librarians\u2019 Experiences; Awards Endowment Task Force Meeting; Awards Committee; Books Panel; Cancer Librarians Section Business Meeting; Clinical Librarians and Evidence-Based Healthcare SIG Business Meeting; Complementary and Alternative Medicine SIG Business Meeting; Data Catalog Collaboration Information Session; Dental Section Business Meeting; Department of Veterans Affairs Librarians SIG Business Meeting #2; EMTS Business Meeting #2; Gaming in Adult Learning SIG Business Meeting; Government Relations Committee; Health Information Professionalism Committee; History of the Health Sciences Section Business Meeting; Hospital Libraries Section (HLS) Executive Board Meeting and Business Meeting and Social; Information Services Curriculum Committee; Instruction and Instructional Design Committee; Latino SIG Business Meeting; LGBQT Health Sciences Librarians SIG Business Meeting; Leadership Curriculum Committee; Libraries in Curriculum SIG Business Meeting; Medical Humanities SIG Business Meeting; Medical Informatics Section Business Meeting; Medical Libraries: Starting from Scratch; MLA Research Training Institute; Molecular Biology and Genomics SIG Business Meeting; New York-New Jersey Chapter Board Meeting; Nursing and Allied Health Resources Section (NAHRS) Business Meeting and Executive Board; Osteopathic Libraries SIG Business Meeting; Pacific Northwest Chapter Business Meeting; Pediatric Librarians SIG Business Meeting; Pharmacy and Drug Information (PDI) Section Business Meeting; Professional Recruitment and Retention Committee; Public Health/Health Administration Section Business Meeting; Public Services Section Business Meeting; Scholarly Communications Committee; Solo Librarians SIG Business Meeting; Technical Services Section Business Meeting; Transitional Sciences Collaboration SIG Business Meeting; Veterinary Medical Libraries Section Business Meeting; and Vision Section SIG Business Meeting. Exhibitor meetings included: Lunch & Learn: How to Conduct Systematic Reviews the JBI Way; and How to Provide a World-Class Systematic Review Service Using Covidence.On Tuesday, May 22, the following groups, sections, and SIGs met: AAHSL Program and Education Committee; Bylaws Committee; Diversity and Inclusion Task Force; education committee chairs joint meeting; Federal Libraries Section Business Meeting; Health Association and Corporate Libraries Section (HACLS) Business Meeting; Information Literacy in Medical Education (ILME) SIG Business Meeting; Information Management Curriculum Committee; Institutional Animal Care and Use SIG Open Discussion; Joint 2018 and 2019 Contributed Content Work Group; Leadership and Management Section Business Meeting; Joseph Leiter NLM/MLA Lectureship Committee; Librarians without Borders\u00ae Committee; Medical Library Education Section (MLES) Business Meeting; Medical Library Group of Northern California and Nevada Business Meeting; Medical Library Group of Southern California and Arizona Business Meeting; Membership Committee; Midcontinental Chapter Meeting and Greet #2; MLA community managers and webmasters; MLA News Editorial Board; Research Section Business Meeting; Rising Stars presentations; Rising Stars program; section treasurers orientation; Social Justice Section Business Meeting; Southern Chapter Executive Committee; Systematic Reviews SIG Informal Meeting; and Technical Services Section Social. Exhibitor meetings included: Lunch & Learn: Elsevier Luncheon for Medical Librarians: Collaboration for Innovation.On Wednesday, May 23, the following groups, sections, and SIGs met: Community Strategic Goal Task Force Meeting 2; Education Annual Programming Committee (EAPC); Grants and Scholarships Committee; and Oral History Committee.Three open forums were held on Sunday, May 20, from 4:30 p.m.\u20135:25 p.m.:MLA Communities Strategic GoalMLA Diversity and Inclusion Strategic GoalMLA InSight Initiative Summit 1 OutcomesThe National Library of Medicine (NLM) Update took place on Tuesday, May 22, 11:00 a.m.\u201311:55 a.m. Joyce E. B. Backus, associate director for library operations, began the session by introducing herself, Patricia F. Brennan, director of NLM, and Amanda J. Wilson, head, National Network Coordinating Office, National Network of Libraries of Medicine (NNLM), all of whom participated in the update.Dr. Brennan presented an explanation of the NLM Strategic Plan, \u201cA Platform for Biomedical Discovery and Data-Powered Health 2017\u20132027.\u201d The three pillars were designed to target the future: (1) accelerate discovery and advance health through data-driven research; (2) reach more people through enhancement, dissemination, and engagement; and (3) build a workforce for data-driven research and health. In discussing the budget, Dr. Brennan said that NLM has received $22,000,000 for new investments in data science, accelerated training for librarians, and platform stabilization. She noted key accomplishments since February 2018.Ms. Backus reported on strategic planning activities and outcomes. She discussed MEDLINE 2022, a 5-year plan to do a behind-the-scenes modernization of MEDLINE and more efficient delivery of information on TOXNET. She introduced PubMed Labs and PubOne that launched in October 2017 and is a test site to try new features for PubMed 2.0, which will be released in December 2018. The NLM website has been refreshed: the PubMed Health Portal will be going away, but PubMed and Bookshelf will still have systematic review and drug information. MedlinePlus now includes Lab Test information. Ms. Backus mentioned several other NLM activities including the DeBakey Fellowship, rare book loans, visiting library and information science students, and NLM associate fellows.JAMA article on the history of NNLM from 1985\u20132015.Ms. Wilson noted NNLM year three activities and illustrated an organizational chart of NNLM. She highlighted projects in health literacy, hurricane relief, funding for classes, and the Wikipedia edit-a-thon. She showed videos of three examples of NNLM activities: University of Arizona, St. Paul, MN, and University of Pittsburgh Medical Center (UPMC). The All of Us public library initiative was also mentioned. Ms. Wilson showed a slide of the The remainder of the session was devoted to questions and answers.The Legislative Update was held on Tuesday, May 22, from 1:00 p.m.\u20131:55 p.m. Cristina Pope, AHIP, chair, MLA Governmental, Relations Committee, and director, Health Sciences Library, State University of New York (SUNY) Upstate Medical, University\u2013Syracuse, moderated the session. Dina Paltoo, interim assistant director for policy development at NLM, presented information on the following: an overview of funding, functions of NLM, NLM\u2019s most heavily used databases, statistics on PubMed Central, statistics on biomedical informatics and data science research, legislation and NLM, and bills and government activities that most affect NLM.Welcome Reception and Opening of the Hall of Exhibits, 5:00 p.m.\u20137:30 p.m.MLA New Members/First-Time Attendees Program and Breakfast, 7:00 a.m.\u20138:55 a.m.Yoga Class, 7:30 a.m.\u20138:30 a.m.Library School Reunion Tea, 2:00 p.m.\u20132:55 p.m.Clinical Librarianship Happy Hour, 5:30 p.m.\u20137:00 p.m.International Visitors Reception, 6:00 p.m.\u20137:00 p.m.Academy of Health Information Professionals Q&A Session, 2:30 p.m.\u20133:25 p.m.Diversity and Inclusion Task Force Fish Bowl, 5:00 p.m.\u20136:25 p.m.Public Librarian Welcome Breakfast and Speed-Networking Event, 7:00 a.m.\u20138:55 a.m.Public Librarians Symposium, Overview and Sessions 1 & 2, 9:00 a.m.\u201310:25 a.m.Public Librarians Symposium, Morning Concurrent Sessions 1 & 2, 11:00 a.m.\u201311:55 a.m.Public Librarians Symposium, Afternoon Concurrent Sessions 1 & 2, 1:00 p.m.\u20131:55 p.m.MLA Book Authors and Prospective Authors Gathering, 2:00 p.m.\u20132:55 p.m.Public Librarians Symposium, Health Literacy Heroes Sessions 1 & 2, 4:30 p.m.\u20135:25 p.m.Silver and Gold Networking Dinner, 6:30 p.m.\u201310:00 p.m.Exhibitors held Sunrise Seminars to provide information and to introduce new products and services. The following seminars were held:Artificial Intelligence (AI) in Health Care: From Adoption to DisruptionCochrane \u201cInside/Outside\u201d: Update from Carol LefebvreEmbase Seminar: Librarian Roles in Teaching Evidence-Based MedicineThe Power of Single Sign-On and the Benefits to AllAmerican Psychological AssociationSpringer Nature Competitive Intelligence: Research Trends in Health CareThree Trends That Eclipse Point-of-Care ToolsTen Technology Showcases were held throughout Sunday, Monday, and Tuesday:Automating the Systematic Review Process: An Overview of DistillerSR\u2019s New Productivity EnhancementsCase Files: Teaching Case CollectionCovering Your Nursing Bases: Research, Decision Support, and CompetenciesSupporting Your Interdisciplinary Care Dream TeamGetting Beyond the Impact Factor: Using Bibliometrics for Research Evaluation at the NIH LibraryTaking Medical Research to the Next Level: 72,987,390 Searches Can\u2019t Be WrongThe Ever-Evolving World of Medical E-BooksFrom Data Standards to DermExpert: The Story of How an Image Collection Learned to ThinkLooking to the Future with EndNoteTop Questions Medical Libraries Ask OpenAthensThe 2017/2018 Education Annual Programming Committee offered the following courses to 236 attendees on May 18 and 19, 2018.Instructors: Julie Glanville, MCLIP, associate director, York Health Economics Consortium, University of York, York, United Kingdom, and Carol Lefebvre, HonFCLIP, independent information consultant, Lefebvre Associates, Oxford, United KingdomCE100 Advanced Searching Techniques and Advanced Strategy Design, Instructors: Karen Gutzman, impact and evaluation librarian, and Patricia L. Smith, impact and dissemination librarian, Galter Health Sciences Library, Feinberg School of Medicine, Northwestern University, Chicago, ILCE200 Dissemination in Action: Communicating Research in a Digital World, Instructors: Sarah Young, senior librarian, Mellon Institute Library, Carnegie Mellon University, Pittsburgh, PA; Jin Wu, emerging technologies librarian, Norris Medical Library, University of Southern California\u2013Los Angeles; and Ayaba Logan, research and education informationist and assistant professor, Medical Libraries, University of South Carolina\u2013CharlestonCE502 Statistics 101: A Primer in Statistical Methods for Health Sciences Librarians, Instructors: Gwen Wilson, health sciences librarian, Mabee Library, Washburn University, Topeka, KS, and Kristen DeSanto, AHIP, clinical librarian, Health Sciences Library, Anschutz Medical Campus, University of Colorado\u2013AuroraCE600 Building Partnerships with Faculty, Clinicians, and Other Stakeholders, Instructors: Erin Eldermire, head, Flower-Sprecher Veterinary Library, Cornell University Library, Ithaca, NY; Sarah Young, senior librarian, Mellon Institute Library, Carnegie Mellon University, Pittsburgh, PA; and Lenny Rhine, FMLA, coordinator, E-Library Training Initiative, Librarians without Borders\u00ae/MLA, Gainesville, FLCE101 Performing Systematic Reviews in Resource-Limited Settings, Instructors: Julie Glanville, MCLIP, associate director, York Health Economics Consortium, University of York, York, United Kingdom, and Carol Lefebvre, HonFCLIP, independent information consultant, Lefebvre Associates, Oxford, United KingdomCE102 Trials without Tribulations: Identifying Clinical Trials for Systematic Reviews and Other Clinical and Research Questions, Instructors: Wichor M. Bramer, biomedical information specialist, Medical Library, Erasmus University Medical Center, Rotterdam, the Netherlands, and Melissa L. Rethlefsen, AHIP, deputy director, Spencer S. Eccles Health Sciences Library, University of Utah\u2013Salt Lake CityCE103 Effectiveness and Efficiency in Exhaustive Searches, Instructors: Rachel Pinotti, AHIP, assistant library director, Education and Research Services, Levy Library, Icahn School of Medicine at Mount Sinai, New York, NY; Antonio P. DeRosa, AHIP, oncology consumer health librarian and assistant librarian faculty, Samuel J. Wood Library and C.V. Starr Biomedical Information Center, Weill Cornell Medicine, New York, NY; and Diana Delgado, AHIP, associate director, User Support, Research and Education, Samuel J. Wood Library and C.V. Starr Biomedical Information Center, Weill Cornell Medicine, New York, NYCE104 Upping Your Reference Game: Technologies and Strategies for Value-Added Reference Services, Instructor: Michele Malloy, research librarian, Congressional Research Service, Library of Congress, Washington, DCCE105 Health Policy Research: Navigating Governmental and Legislative Sources, Instructors: Julia M. Esparza, AHIP, head, User Education and Outreach Services; Montie\u2019 L. Dobbins, head, User Access Services/Circulation; and David C. Duggar, AHIP, head, Library Liaison Program; Health Sciences Library, Louisiana State University (LSU) Health\u2013Shreveport; and Alexandria (Lexi) Brackett, AHIP, clinical support librarian, Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CTCE300 Not Just Numbers: Teaching Students to Think Using Practical Curriculum Exercises, Instructor: Jessica Sender, librarian, College of Nursing, Michigan State University\u2013East LansingCE301 Innovations in Nursing Information Literacy: New Technologies, Approaches, and Ideas, Instructors: Andy Hickner, web services librarian, Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, and Susanna Galbraith, virtual services librarian, Health Sciences Library, McMaster University, Hamilton, ON, CanadaCE302 Peeking Under the Hood: Understanding, Assessing, and Improving Your Library\u2019s Website and LibGuides, Instructors: Jamie Conklin, research and education librarian, and Megan von Isenburg, AHIP, associate dean, Library Services and Archives, Medical Center Library & Archives, Duke University, Durham, NCCE303 Evidence-Based Teaching: Finding and Applying the Best Evidence to Instruction, Instructors: Heidi Heilemann, AHIP, associate dean and knowledge management director, Lane Medical Library and Knowledge Management Center, Stanford University, Stanford, CA; M.J. Tooey, AHIP, FMLA, associate vice president, Academic Affairs, and executive director, Health Sciences and Human Services Library, University of Maryland\u2013Baltimore; and Gabriel Rios, director, Ruth Lilly Medical Library, Indiana University\u2013IndianapolisCE400 Do You Want to Be a Library Director? Knowledge, Skills, and Career Paths for Library Leaders, Instructor: Erinn Aspinall, AHIP, strategic initiatives librarian and communications coordinator, Bio-Medical Library, Health Sciences Libraries, University of Minnesota\u2013MinneapolisCE401 Digital Storytelling: Communication for Greater Impact, Instructor: Ayaba Logan, research and education informationist and assistant professor, Medical Libraries, Medical University of South Carolina\u2013CharlestonCE500 What Did You Hear? Qualitative Data Analysis, Instructors: Marci Brandenburg, bioinformationist, and Jean Song, assistant director, Academic and Clinical Engagement, Taubman Health Sciences Library, University of Michigan\u2013Ann ArborCE501 Introduction to Visualization Principles, Instructor: Lisa Federer, AHIP, research data informationist, NIH Library, National Institutes of Health, Bethesda, MDCE503 Introduction to Data Analysis and Visualization with R, Instructors: David A. Nolfi, AHIP, health sciences librarian and library assessment coordinator, Gumberg Library, Duquesne University, Pittsburgh, PA, and Carolyn Schubert, interim director, Research and Education Services, and health sciences and nursing librarian, Carrier Library, James Madison University, Harrisonburg, VACE601 Learning to Liaise with Health Professions, The online itinerary planner (sponsored by Wolters Kluwer) allowed attendees to peruse programs and events online. Complimentary WiFi was available throughout the Hyatt Regency Atlanta courtesy of The JAMA Network. Live streaming was available on Twitter using the hashtag #MLANET18, and volunteer bloggers, the Local Assistance Committee, and the 2018 National Program Committee contributed to the official meeting blog with meeting tips, announcements, and more. For those seeking new jobs and prospective employers, the Job Placement Center was open from Saturday through Tuesday, and the MLA Resume Clinic was available Saturday through Monday. The Hall of Exhibits was open Saturday evening through Monday.AppendixClick here for additional data file.AppendixClick here for additional data file."} +{"text": "Transcranial magnetic stimulation (TMS) has been evaluated as an effective treatment option for patients with major depressive disorder. However, there are limited studies that have evaluated the efficacy of TMS for other neuropsychiatric disorders such as anxiety and trauma\u2010related disorders. We reviewed the literature that has evaluated TMS as a treatment for anxiety and trauma\u2010related disorders.n\u00a0=\u00a0520) evaluating TMS in anxiety and trauma\u2010related disorders were screened and a small subset of these that met the eligibility criteria (n\u00a0=\u00a017) were included in the systematic review, of which nine evaluated TMS in posttraumatic stress disorder (PTSD), four in generalized anxiety disorder (GAD), two in specific phobia (SP), and two in panic disorder (PD). The meta\u2010analysis was performed with PTSD and GAD since PD and SP had an insufficient number of studies and sample sizes.We searched for articles published up to December 2017 in Embase, Medline, and ISI Web of Science databases, following the Preferred Items for Reporting of Systematic Reviews and Meta\u2010Analyses (PRISMA) statement. Articles and GAD , including applying high frequency over the right dorsolateral prefrontal cortex. Since few studies have evaluated TMS for SP and PD, few conclusions can be drawn.Our meta\u2010analysis suggests that TMS may be an effective treatment for GAD and PTSD. We reviewed TMS as a treatment for anxiety disorders and PTSD.TMS presented large effect sizes as a treatment for PTSD and GAD.Follow\u2010up studies in GAD showed improvement of patients after TMS.Future studies should evaluate maintenance treatment.1Transcranial magnetic stimulation (TMS) is a safe, effective, noninvasive, and nonconvulsive neuromodulation therapy cleared by the U.S. Food and Drug Administration (FDA) for the treatment of the major depressive disorder (MDD) since 2008 until it reached the neurons of the cortex. At this level, the magnetic field converts back into a (secondary) electrical current able to depolarize neurons and force an action potential, which will then travel from synapse to synapse across an entire functional circuit of interest following the recommendations of the Preferred Items for Reporting of Systematic Reviews and Meta\u2010Analyses (PRISMA) statement , because this is the minimum number of sessions to induce plasticity and improve symptoms for long term, while in SP a short\u2010term effect may be useful since the symptoms are more punctual , response and remission rates, and period of follow\u2010up. We contacted authors for additional data whenever necessary and we greatly appreciate the contributions of Dr. Zangen, Osuch, and Watts . In case of moderate or high heterogeneity (I2> 50%), a sensitivity analysis was done to determine the impact of each study on the results and a meta\u2010regression was performed to evaluate the influence of each TMS parameter at a time. For studies without the SD of the total score of the primary outcome, the largest similar SD found in other studies was repeated, according to the Cochrane Handbook for Systematic Review . Of those, 123 were duplicate references, and 37 were not in the English language. The remaining 483 references underwent a title and abstract analysis after which 419 were excluded. Finally, 64 articles were recovered for full\u2010text reading. After this process, only 17 articles met the inclusion criteria of articles that assessed TMS as a treatment for anxiety disorders or PTSD ; therefore, the difference between studies is by chance. Possible causes of publication bias were tested with the funnel plot . Table The overall effect size was \u22122.06 , widely favoring active rTMS treatment. There was low heterogeneity . The funnel plot is symmetric , suggesting that publication bias is unlikely. The reported dropouts and the amount of these that are due to side effects are in Tables The treatment of PTSD with TMS is the most studied among the conditions of interest. Nine studies were included in this meta\u2010analysis or sham (n\u00a0=\u00a013) rTMS. They applied 1\u00a0Hz, at 110% RMT, and 1,800 pulses/session, over the rDLPFC, for 4\u00a0weeks. After the last week of treatment, patients in active rTMS had a significant improvement in their PD but not in their MDD. This study was followed by four additional weeks of an open\u2010label treatment in which patients in the sham group could undergo active treatment and patients in the active group could receive additional treatment. After this second phase, patients continued to improve from PD and improved from MDD. Subsequently, at a 6\u2010month follow\u2010up, patients showed sustained improvement of both disorders aim that are informative in the context of this review. These studies evaluated rTMS or excitatory intermittent theta burst stimulation (iTBS) as a treatment for SP or sham (n\u00a0=\u00a019) rTMS applied before a virtual reality exposure to heights in two groups of individuals diagnosed with acrophobia. The protocol consisted of two active sessions of 20\u00a0min of rTMS with 10\u00a0Hz, at 100% RMT, 4\u00a0s on and 26\u00a0s off, with 1560 pulses per session, and the sessions were 1\u00a0week apart. At the end, anxiety and avoidance ratings decreased in the active group in fear extinction included in this meta\u2010analysis presented adverse events , a number of trials have been published particularly for GAD and PTSD. Our meta\u2010analysis concludes an overall positive therapeutic effect of TMS for these two conditions. These results suggest (but do not prove) an advantage of right over lDLPFC stimulation, and the possible therapeutic advantage of high\u2010frequency stimulation to the rDLPFC. Based on the studies that reported side effects, TMS demonstrated to be safe and well tolerated in the treatment of anxiety disorders and PTSD but reports of side effects were inconsistent. In summary, the result of this meta\u2010analysis confirms the therapeutic potential and safety of TMS for GAD and PTSD and generates some hypotheses for upcoming prospective, larger, and appropriately powered randomized controlled trials to confirm these results.. AAN reports the following disclosures: Consultant \u2010 Abbott Laboratories, Alkermes, American Psychiatric Association, Appliance Computing Inc. (Mindsite), Basliea, Brain Cells, Inc., Brandeis University, Bristol Myers Squibb, Clintara, Corcept, Dey Pharmaceuticals, Dainippon Sumitomo (now Sunovion), Eli Lilly and Company, EpiQ, L.P./Mylan Inc., Forest, Genaissance, Genentech, GlaxoSmithKline, Healthcare Global Village, Hoffman LaRoche, Infomedic, Intra\u2010Cellular Therapies, Lundbeck, Janssen Pharmaceutica, Jazz Pharmaceuticals, Medavante, Merck, Methylation Sciences, NeuroRx, Naurex, Novartis, PamLabs, Parexel, Pfizer, PGx Health, Otsuka, Ridge Diagnostics Shire, Schering\u2010Plough, Somerset, Sunovion, Takeda Pharmaceuticals, Targacept, and Teva; consulted through the MGH Clinical Trials Network and Institute (CTNI) for Astra Zeneca, Brain Cells, Inc, Dianippon Sumitomo/Sepracor, Johnson and Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Shire, Schering\u2010Plough, Targacept and Takeda/Lundbeck Pharmaceuticals, NeuroRx Pharma, Pfizer, Physician's Postgraduate Press, Inc. Grants/Research support \u2010 American Foundation for Suicide Prevention, AHRQ, Brain and Behavior Research Foundation, Bristol\u2010Myers Squibb, Cederroth, Cephalon, Cyberonics, Elan, Eli Lilly & Company, Forest, GlaxoSmithKline, Intra\u2010Cellular Therapies, Janssen Pharmaceuticals, Lichtwer Pharma, Marriott Foundation, Mylan, NIMH, PamLabs, Patient Centered Outcomes Research Institute (PCORI), Pfizer Pharmaceuticals, Shire, Stanley Foundation, Takeda/Lundbeck, and Wyeth\u2010Ayerst. Honoraria \u2010 Belvoir Publishing, University of Texas Southwestern Dallas, Brandeis University, Bristol\u2010Myers Squibb, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, Health New England, Harold Grinspoon Charitable Foundation, IMEDEX, International Society for Bipolar Disorder, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, MGH Psychiatry Academy, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, University of Wisconsin at Madison, APSARD, ISBD, SciMed, Slack Publishing and Wolters Klower Publishing, ASCP, NCDEU, Rush Medical College, Yale University School of Medicine, NNDC, Nova Southeastern University, NAMI, Institute of Medicine, CME Institute, ISCTM, World Congress on Brain Behavior and Emotion, Congress of the\u00a0Hellenic Society\u00a0for Basic and\u00a0Clinical Pharmacology, ADAA. Stock \u2010 Appliance Computing, Inc. (MindSite); Brain Cells, Inc., Medavante. Copyrights \u2010 Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Speaker Bureaus \u2010 none since 2003. JAC is a scientific advisor for Apex Neuroscience. GK has received research support from Astra\u2010Zeneca, Bristol\u2010Myers Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sanofi/Synthelabo, Sepracor Inc., Pfizer Inc, UCB Pharma, and Wyeth\u2010Ayerst Laboratories, Agency for Healthcare Research and Quality (AHRQ) Grant R01 HS019371\u201001, and Takeda Pharmaceuticals.\u00a0He has been an advisor or consultant for Astra\u2010Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma, and Wyeth\u2010Ayerst Laboratories. GK has been a speaker for Astra\u2010Zeneca, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sepracor Inc., and Wyeth\u2010Ayerst Laboratories. The other authors have no conflicts of interest to declare.AKG receives research support from NIMH"} +{"text": "GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980\u20132015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388: 1459\u20131544\u20142016: In this Article, Tea Lallukka, Anoushka Millear, and Amanda Pain should have been listed as authors. The affiliation details for Monica Cortinovis and Giorgia Giussani have been updated. An affiliation and funding statement have been added for Simon I Hay. These corrections have been made to the online version as of Jan 5, 2017."} +{"text": "Scientific Reports 10.1038/s41598-019-42919-y, published online 01 May 2019Correction to: In the original version of this manuscript, the incorrect isolate ID was provided for NCHW8.In addition, the Article contained an error in Affiliation 6, which was incorrectly given as \u2018Department of Bacteria, Parasites and fungi, Staten Serum institut, copenhagen, Denmark\u2019. The correct affiliation is listed below:Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, DenmarkThese errors have now been corrected in the HTML and PDF versions of the article."} +{"text": "Background: The number of papers published by an institution is acknowledged as an easy-to-understand research outcome. However, the quantity as well as the quality of research papers needs to be assessed.Methods: To determine the relation between the number of published papers and paper quality, a survey was conducted to assess publications focusing on interventional clinical trials reported by 11 core clinical research hospitals. A score was calculated for each paper using Syst\u00e8me d\u2019interrogation, de gestionet d\u2019analyse des publications scientifiques scoring system, allowing for a clinical paper quality assessment independent of the field. Paper quality was defined as the relative Journal impact factor (IF) total score/number of papers.Results: We surveyed 580 clinical trial papers. For each of the 11 medical institutions (a\u2013k), respectively, the following was found: number of published papers: a:66, b:64, c:61, d:56, e:54, f:51, g:46, h:46, i:46, j:45, k:45 ; total Journal IF: a:204, b:252, c:207, d:225, e:257, f:164, g:216, h:190, i:156, j:179, k:219 ; relative Journal IF total score: a:244, b:272, c:260, d:299, e:268, f:215, g:225, h:208, i:189, j:223, k:218 ; and paper quality : a:3.70, b:4.25, c:4.26, d:5.34, e:4.96, f:4.22, g:4.89, h:4.52, i:4.11, j:4.96, k:4.84 . Additionally, no significant relation was found between the number of published papers and paper quality .Conclusions: The number of published papers does not correspond to paper quality. When assessing an institution\u2019s ability to perform clinical research, an assessment of paper quality should be included along with the number of published papers. Syst\u00e8me d\u2019interrogation, de gestionet d\u2019analyse des publications scientifiques , is used to calculate a score that objectively assesses paper quality of the journal in which the article has been published . However quality , allowinFor this study, 580 clinical trial papers were surveyed to investigate the relation between number of papers and paper quality . Clinical trial papers were retrieved from 11 core clinical research hospitals in Japan.Based on data published on the website of the Ministry of Health, Labour and Welfare, a descriptive research was conducted to compare the quantity and quality of clinical trial papers published by 11 core clinical research hospitals. A relative Journal IF score, based on the SIGAPS scoring system, was used to assess paper quality.In Japan, core clinical research hospitals are appointed by the Medical Care Act. They play a central role in physician-led clinical trials and in clinical research developed according to international standards toward the development of innovative pharmaceuticals and medical instruments in Japan. These hospitals support clinical research developed in other medical institutions and play a key role in optimizing next-generation healthcare by enhancing the quality of clinical research in those medical institutions where joint research efforts are conducted.The Ministry of Health, Labour and Welfare grants approval for core clinical research hospitals , which aTo meet former clinical research performance requirements, core hospitals must have submitted a minimum of 45 clinical trial papers published over the last three years. All papers were required to be published in PubMed. Requirements for approval of hospitals as core clinical research institutions, as determined by the Ministry of Health, Labour and Welfare, only include the development of interventional clinical trials, excluding observational studies.For study purposes, all clinical trial papers submitted until November 2018 by 11 core hospitals were extracted from the Ministry of Health, Labour and Welfare website and examined. Additionally, a list of clinical trial publications from each study hospital was retrieved from a 2017 business report of core clinical research hospitals published by the Ministry of Health, Labour and Welfare .Using PubMed \u201cJournalTitle,\u201d \u201cMedAbbr,\u201d and \u201cIsoAbbr,\u201d search strings, both printed and online International Standard Serial Number information was obtained by comparing journals in which papers listed in the business report were published. If a match between PubMed records and journal list content could not be found, a visual check was conducted whenever appropriate.Relative Journal IF score was calculated based on the SIGAPS scoring system. Research fields of each clinical trial papers were initially categorized based on the Web of Science Category. A Journal IF percentile was then calculated for each field, and both a rank and a score were attributed to each journal based on that percentile Table 1.For journals with multiple IF percentiles, the highest value was selected. Additionally, paper quality was defined as relative Journal IF total score/number of papers.SIGAPS components include the journal\u2019s rank and the author\u2019s rank, including first or last author (4 points), second or second-to-last author (3 points), third author (2 points), or any other contributing author (1 point) with a weighting factor. However, to approve a clinical research hospital, the Ministry of Health, Labour and Welfare requires that the first author of a clinical publication belongs to the considered institution. For this reason, in this study the relative Journal IF score was calculated based on only the journal\u2019s rank.The correlation between paper quantity and quality was estimated through the Spearman\u2019s correlation coefficient. Aggregation and analysis of all data was performed using SAS ver. 9.4 .Overall, 580 clinical trial publications from the last three years were surveyed. The number of published papers, total Journal IF, relative Journal IF total score, and paper quality for each of the 11 medical institutions investigated are shown in A comparison between the number of published papers and paper quality is shown in We performed additional analyses with data excluding 44 protocol papers. The following was found: number of published papers: a:41, b:56, c:61, d:54, e:54, f:51, g:45, h:45, i:40, j:44, k:45 ; total Journal IF: a:166, b:221, c:207, d:218, e:257, f:164, g:213, h:188, i:147, j:175, k:219 ; relative Journal IF total score: a:180, b:243, c:260, d:289, e:268, f:215, g:221, h:205, i:172, j:219, k:218 ; and paper quality : a:4.39, b:4.34, c:4.26, d:5.35, e:4.96, f:4.22, g:4.91, h:4.56, i:4.30, j:4.98, k:4.84 . No significant relation was also found between the number of published papers and paper quality .In this study, 580 clinical trial papers reported by 11 core clinical research hospitals in Japan were surveyed to examine the relation between quantity and quality of publications. Results showed no significant relation between the number of papers published by a hospital and the quality of those papers. Therefore, an evaluation of both the number and quality of published papers should be performed when assessing an institution\u2019s competence to execute clinical research based on their scientific publications.This study employed a quality assessment metric indicator calculated based on the SIGAPS scoring system. SIGAPS was developed in 2002 at the French University Hospital, Lille (CHU) . The SIGIn this study, the only paper quality assessment measure used was the relative Journal IF score. However, other metrics must be considered. The citation index is one such candidate . HoweverWhen assessing the quality of medical publications, it is also necessary to account for their contribution to the development of treatment guidelines. Medical treatment guidelines are developed by field specialists, and they provide the latest evidence-based data on medical practices and procedures in the clinical setting. Areas covered ranged from disease pathophysiology to prevention, diagnosis, treatment, and rehabilitation, and guidelines in each of these areas contribute to improve quality standards of medical treatment. Medical treatment guidelines are important contributions to healthcare, and publications focusing them should be considered as high-quality, regardless of the journal\u2019s IF or citation index.The method for calculating relative Journal IF based on the SIGAPS scoring system that was developed in France is clear and technically acceptable in any country other than France, as described in the Methods section. However, there are issues regarding Journal IF that still need to be solved. One challenge is the adequate assessment of negative studies. For example, clinical researchers tend not to publish negative studies with small sample sizes. This could cause publication bias. Since negative studies with small sample sizes may have a very high social significance, there is a need to create a mechanism to appropriately incorporate the value of negative studies with small sample sizes in Journal IF.Although the focus of this study was paper quality assessment, it is equally important to develop objective metric indicators for quality assessment of clinical research itself. Months or years can go between completion of clinical studies and publication of their results. Therefore, in absence of a metric indicator for paper quality assessment, quality assessment of the ongoing or recently completed clinical study is not possible. Developing metric indicators to assess the quality of clinical research, and not only the quality of resulting publications, is therefore an unmet and urgent need. As the next step, an index should be added that can objectively evaluate the quality of the research process, including the number of patients enrolled, speed of enrollment, rate of satisfaction with enrollment, number of protocol deviations, and number of protocol amendments.The present study has several limitations, including undeniable social issues. The first limitation is the method used to calculate the relative Journal IF score. This method attributes a score by categorizing a paper based on the percentiles for its field, and a concern exists that the maximum and minimum Journal IF in the same percentile may be treated as the same score.The second limitation relates to policy differences for assessment of track records of research institutions, which constitutes an undeniable social issue. When assessing faculty track records, some research institutions may prioritize paper quality over the number of published papers, others may take the opposite approach, and others may even prioritize citations instead. Overcoming these inconsistencies will require the development of metric indicators combining number of papers and relative Journal IF scores with citation indexes or h-indexes in a well-balanced fashion.The third limitation is the impact of research fields considered, at certain times, as \u201cfashionable.\u201d This also constitutes an indisputable social issue. At different time periods, research in popular fields may register great advances, and government agencies and foundations tend to apply their budgets accordingly. Research institutions that can adapt to such trends are likely to experience an increase, both in the number of published papers, as in paper quality. Counteracting this trend-driven impact is difficult. For example, in the field of rare and incurable diseases, the Government of Japan\u2019s \u201cAct on Medical Care for Patients with Intractable Diseases,\u201d passed on May 23, 2014, promoted a reform and the establishment of a sustainable social insurance system. The law went into effect on January 1, 2015, using consumption taxes to create funding for healthcare subsidies and a stable healthcare subsidy system for patients with rare and incurable diseases . ResearcThe fourth limitation is management of protocol papers. Because the approval requirements for core clinical research hospitals include protocol papers, a total of 44 protocol papers have been included in this study . Although these have several benefits, such as deterring publishing bias, preventing similar research, and giving hope to patients regarding the possibility of new or innovative treatments, protocol papers are published at the start of research, prior to result generation. Therefore, their quality should be evaluated separately from that of result-generating publications. We performed additional analyses with the data, excluding the 44 protocol papers. The results revealed a trend similar to that of the overall results. However, an analysis of protocol publications alone was not performed this time because of the limited number available, which was 44.The fifth limitation is the evaluation of open access journals, which are known to have a higher citation impact than closed journals . Future Finally, the relation between paper quantity and quality was only assessed for interventional clinical trials in this study. To address this issue, a subsequent study targeting both interventional and observational studies is currently being planned.This study revealed that the quantity of papers published by an institution does not necessarily correspond to their quality. When assessing an institution\u2019s ability to execute clinical research, assessment of paper quality should be included alongside assessment of the number of published papers.ynishiza@juntendo.ac.jpThe datasets analyzed in this manuscript are not publicly available. Requests to access the datasets should be directed to Yuji Nishizaki, RU and YN designed this study in whole and drafted this manuscript. RU contributed to data collection. NaoY and SN contributed to statistical analysis. YH, SS, TO, SY, KM, NaoY, MN, KF, SN, YS, NatY, and PD provided advice on the interpretation of results. YN and HD provided a critical revision of the manuscript for intellectual content and gave the final approval for the submitted manuscript. All authors have read and approved the final manuscript.The study was supported by a grant from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP181k1903001 from April 1, 2018 to March 31, 2019.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This article presents the raw data in relation to the status of, and the distribution of, the 41 marine algal species occurring around and within the An Thoi coral reef strictly protected zone, Phu Quoc Marine Protected Area. The data, which were collected in May 2017, include the detailed description of the locations, the oceanographical conditions, and the photographs of the 41 marine algal species. For more insight, please see \u201cMarine algal species and marine protected area management: A case study in Phu Quoc, Kien Giang, Vietnam\u201d Huynh and Nguyen, 2019. A total"} +{"text": "The data was obtained to present the environmental and occupational exposure to lead in Iranian populations based on the published articles. To acquire the data, online resources including Google Scholar, Magiran, SID, Iranmedex, PubMed, and Science Direct were searched and 104 articles were found out of which 70 that focused on the level of lead in blood, urine, milk, and hair of different Iranian populations were selected. Since the results of the studies were not homogenous, it was not possible to carry out a meta-analysis. The average blood lead level (BLL) among workers, ordinary people, patients with specific diseases, addicts, and pregnant women, women in labor, infants, and children are presented in this article. The average BLL was compared to the standards. Specifications TableValue of the data\u2022The data provides information on the level of lead exposure among different Iranian groups, and is important for scientific community.\u2022The data clarifies protective, managerial, and policy-making measures of the risks involved with lead exposure more than before.\u2022The data can be useful as it collects all the available information about the blood lead level amount Iranians.12The data is based on the articles that were sporadically carried out on certain groups and different cities and published in domestic and foreign journals. The articles were selected from different databases including Google Scholar, Magiran, SID, Iranmedex, PubMed, and Science Direct. While searching the articles, keywords like lead, occupational exposure to lead, lead measuring, human lead contamination, BLL, blood lead level, lead poisoning, lead toxicity, lead exposure were used and their Persian equivalents in Persian websites. All articles published by March 20, 2014 were included. First, all articles on lead exposure carried out in Iran were collected. At this stage, all articles that contained the mentioned keywords in their title or abstract were included in the primary list. Afterwards, a checklist of necessary study information, including study location, study year, sample environment, sample size, and average blood lead level (BLL), was prepared for final evaluation. Searching and extracting of the data was independently carried out by one person. A total of 104 articles that were available by March 20, 2014 were examined. Out of the 104 articles, 70 that were referable were taken used workers, ordinary people, patients with specific diseases, addicts, and pregnant women, women in labor, infants, and children."} +{"text": "The authors wish to make the following corrections to this paper :The 5th author, Steven C. Katz was affiliated with the Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA. The authors would like to add the following 4th affiliation to Steven C. Katz: \u201cRoger Williams Medical Center, Providence, RI 02908, USA\u201d The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the published article, there was an error in affiliation 9. Instead of \u201cUF de Neurobiologie, Centre Biologie Pathologie du CHU-Lille, Lille, France,\u201d it should be \u201cUniv Lille, Inserm, UMRS 1172, LabEx DISTALZ, Lille, France.\u201dAdditionally, St\u00e9phanie Bombois was not included as an author in the published article. The corrected Author Contributions Statement appears below.\u201cED, DG, AG, CB, BA, and SL performed measurements and collected data. J-SV performed statistical analysis. FP, LB, SS-M, A-SR, OH, and JE supervised the study. SB collected data revised the manuscript; Final approval of the version to be published; and is an Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u201dThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Tctively) , and ranve for A ,7. As thve for A ,6,7, andve for A ,13,14,152NH- moieties, which can participate in multiple interactions with metal ions, amino acid residues, DNA or RNA moieties present in various biomolecules acting as drug targets [Indeed, the sulfonamides constitute an important class of drugs, with many types of pharmacological agents possessing antibacterial , anti-ca targets ,28,29,30 targets ,24,25,26Molecules is in fact a nice example of this multitude of possible applications of the sulfonamides, with the wide range of targets to which they bind, diverse synthetic procedures and pharmacological applications, some of which highly innovative, for many representatives of this interesting class of pharmacologic agents. The first contribution is a nice review article [The following special issue of article from Sil article .Mycobacterium species, such as M. avium, M. kansassii, some of them showing remarkable activity [Considering the fact that the sulfonamides were the first antibacterials ,32, due activity .Burkholderia pseudomallei, and the inhibition of these enzymes with a range of more than 40 sulfonamides and sulfamates. Indeed, due to the relevant problem of drug resistance to commonly used antibiotics, the inhibition of CAs from pathogenic organisms started to be considered as an alternative, innovative approach for finding new such pharmacologic agents [The next three papers in the special issue ,38,39 dec agents .The next paper presents2NH2) which incorporate a 1-benzhydrylpiperazine tail, connected to the sulfonamide scaffolf by means of \u03b2-alanyl or nipecotyl spacers was reported and investigated for the inhibition of CAs of human (h) origin, such as hCA I, II, IV and IX. Some of these isoforms are established drug targets, but many sulfonamide or sulfamide inhibitors show little selectivity when inhibiting them. Some of the new sulfamides reported in this paper did show some selective inhibitory profile, mainly against hCA I, which has been rationalized by using computational methods [In the paper by Berrino et al. a new se methods .The next paper in the special issue investigMarciniec et al. present In the paper by Lin et al. sulfadiaIn conclusion, the present special issue presents an interesting collection of high quality papers which underline the many potential applications of the simple, sulfonamide structural motif, a highly used, almost magic moiety in the tool kit of medicinal chemists."} +{"text": "Molecules. Two inadvertent errors were found from Table 2 footnotes section:The authors wish to make the following corrections to this paper published in Footnote k states that \u201ck = Tripeptide containing Arg, Glu and Val; or Arg, Asp and Leu or Ile; or Gln, Gln and Lys or a tetrapeptide containing Ala, Ala, Asp and Lys; or Ala, Gln, Gly and Lys or a pentapeptide containing Ala, Ala, Gly, Gly and Lys\u201d. However, it should be \u201ck = Tripeptide containing Arg, Glu and Val; or Arg, Asp and Leu or Ile; or Gln, Gln and Lys or a tetrapeptide containing Ala, Ala, Asn and Lys; or Ala, Gln, Gly and Lys or a pentapeptide containing Ala, Ala, Gly, Gly and Lys\u201d.Footnote n states that \u201cn = Tripeptide containing Ala, Glu and Val; or Glu, Glu and Leu or Ile; or Pro, Thr and Thr; or Ala, Asp and Leu or Ile; or an acetylated tripeptide containing Gly, Ser and Leu and Ile; or Gly, Thr and Val; or the methyl ester of a tripeptide containing Ala, Asp and Val or Asp, Gly and Leu or Ile\u201d. However, it should be \u201cn = Tripeptide containing Ala, Glu and Val; or Glu, Gly and Leu or Ile; or Pro, Thr and Thr; or Ala, Asp and Leu or Ile; or an acetylated tripeptide containing Gly, Ser and Leu or Ile; or Gly, Thr and Val; or the methyl ester of a tripeptide containing Ala, Asp and Val or Asp, Gly and Leu or Ile\u201d.These changes have no material impact on the conclusions of our paper. We apologize for any inconvenience to our readers."} +{"text": "An introduction to a series of essays honoring Erich Meyerhoff (1919\u20132015), AHIP, FMLA, who was active in and contributed to the Medical Library Association for generations. Journal of the Medical Library Association (JMLA), to catch a glimpse of him and understand why he is honored with a festschrift sponsored by the Fellows of the Medical Library Association (MLA).A few times in each generation, we count ourselves fortunate if we have had the opportunity to know an extraordinary individual. Such an individual was Erich Meyerhoff, AHIP, FMLA (1919\u20132015), who marked his time not simply by living a very long life, but by doing, creating, enabling, and inspiring those around him. He had a passion for his profession and the individuals who made up that profession. Those of us who were not fortunate to know him personally now have the opportunity, through the series of essays published in this issue of the JMLA, provided an overview of his career and, most notably, comments from his peers [Erich was active in and contributed to MLA for generations. His legacy is one of unparalleled support for and encouragement of MLA and its members. His obituary, published in is peers . DescripThe series of essays in this festschrift provides a snapshot of an extraordinary individual who exemplified professionalism and an abiding faith in social justice and the possibilities of what an organization such as MLA could achieve in the twentieth and twenty-first centuries. This festschrift is meant not only to honor Erich, but to provide an example of a professional life well lived for current and future members of MLA. His activities and accomplishments were recognized by MLA through the Marcia C. Noyes Award, the Janet Doe Lectureship, and MLA Fellowship, but there was much more to Erich than these important awards or his longevity.In their essay, \u201cErich Meyerhoff: A Man for All Medical Librarians,\u201d Judith Messerle, AHIP, FMLA, and Lucretia W. McClure, AHIP, FMLA, provide a sketch of his life, education, career, and accomplishments, which spanned many significant developments in health sciences librarianship . They noUnion Catalog of Medical Periodicals and lasted as a resource center and service bureau from 1960 to 2003.Patricia E. Gallagher, AHIP, FMLA, traces the development of the Medical Library Center of New York in her essay, \u201cLibrary Resource Sharing and the Medical Library Center of New York\u201d . The cenElaine Russo Martin, FMLA, defines and reviews democratic librarianship in her essay, \u201cDemocratic Librarianship: The Role of the Medical Library in Promoting Democracy and Social Justice\u201d . ThroughWayne J. Peay, FMLA, and Helen-Ann Brown Epstein, AHIP, FMLA, update the now historic tenth Janet Doe Lecture, which Erich presented in 1977, in their essay, \u201cThe Tenth Doe Lecture: A Forty-Year Perspective: Still Relevant after All These Years\u201d . The lecFinally, Stephen J. Greenberg, AHIP, provides a window into the world of historical writing and how it changed over the course of Erich\u2019s life in his essay, \u201cMedical History: As It Was; As It Will Be\u201d . GreenbeThis series of essays honoring Erich Meyerhoff grew out of discussions of the MLA Fellows group during their annual meeting in conjunction with the MLA annual meeting. A small task force was established to define topics for the festschrift essays and engage authors. I thank the members of the Meyerhoff Task Force: Helen-Ann Brown Epstein, AHIP, FMLA, Patricia E. Gallagher, AHIP, FMLA, Stephen J. Greenberg, AHIP, J. Michael Homan, AHIP, FMLA (chair), and Lucretia W. McClure, AHIP, FMLA.J. Michael Homan, AHIP, FMLA,homan@mayo.edu, Emeritus Director of Libraries, Assistant Professor of Biomedical Informatics, and Emeritus Consultant, Health Sciences Research, Mayo Clinic, Rochester, MN"} +{"text": "This popular annual session will provide cutting-edge information on what the 116th Congress has and has not accomplished to date, and what may be left for this year. Speakers will discuss key issues such as Social Security, Medicare, Medicaid, and the Older Americans Act, caregiving, the National Institutes of Health. Hill staffers, advocates, and lobbyists will present."} +{"text": "There is an error in the affiliation of author Halina Wi\u015bniewska. The affiliation should be: Institute of Plant Genetics, Polish Academy of Sciences, Pozna\u0144, Wielkopolskie Voivodeship, Poland."} +{"text": "The article titled \u201cThe Past, Present, and Future of Public Health Surveillance\u201d was founCastillo-Salgado , which iDeclich and Carter , which iTeutsch and Churchill , which iFreeman et al. , which iBrachman and Thacker , which iMcNabb et al. , which iJohnson and Heymann , which iWork by other authors:Choi , which iChoi and Pak , which iAuthors' own work:"} +{"text": "On the basis of pooled data from studies of theNational Heart, Lung and Blood Institute (1995-2012), it is estimated that within oneyear after a first myocardial infarction, 18% of males and 23% of females will die, andthe median survival time is, at \u2265 45 years of age, 8.2 years for males and 5.5for females.3 The underestimation ofcardiovascular risk among women frequently resulted in a more conservative treatment andcontributed to poorer outcomes.4 In thelast decade, several studies have assessed the issue of gender disparities in thediagnosis, treatment, and outcomes of acute coronary syndromes (ACS).2,4 In this context, the study by Soeiro et al.5 contributes to the understanding of thisissue by presenting data from a Brazilian registry of ACS.Coronary artery disease (CAD) was considered, for years, a \"male disease\u201d, a concept thatinfluenced diagnostic and clinical decision-making processes.In this multicenter registry, the primary endpoint was in-hospital, all-cause mortality,and the secondary endpoint was the combination of cardiogenic shock, death,reinfarction, ischemic stroke and bleeding during a mean follow-up of 8 months. Justlike any registry, it has limitations, such as the absence of data on other diseaseslike cancer, as well as on the differences in post-discharge management, adherence totreatment, among others, all which might influence survival in any group. Nonetheless,it has a large number of patients and may offer aninteresting view of the Brazilian scenario of gender differences in ACS.6Unfortunately, data on symptoms at presentation are not available. It is known that, inACS, women are less likely to present with classical angina symptoms, which may lead tounder and/or misdiagnoses in women, and in turn may explain the worse outcomes,particularly in younger women.6,7Accordingly, in the present study, it was noteworthy that percutaneous coronaryinterventions and coronary artery bypass grafting were more frequently performed in menthan in women.Of note, at presentation, women less often had ST-elevation and multivessel CAD than men,but were older and more frequently diabetic, dyslipidemic and hypertensive. These dataare in line with other studies.4,8 On the other hand, similar short-termoutcomes in men and women have also been reported,9 especially after adjustment for clinical differences and theseverity of angiographic disease.10Gaui et al,11 in an analysis ofBrazilian death certificates from 2004 to 2011, reported higher proportional mortalitydue to acute ischemic heart disease in women from the Northeastern region, aged 40-49years, than in men, despite overall lower proportional mortality. Globally, thisdemonstrates that the outcomes of ACS in women are at least equivalent to those of men,if not worse.Regarding outcomes, there were no significant differences between men and women. Thiscontrasts to other studies in which women had worse outcome after ACS, what has beenattributed, among other factors, to older age or the presence of more comorbidities inwomen.The longstanding \u201cknowledge gap\u201d on CAD in women, both on the part of physicians and ofpatients, has created inequalities in healthcare access and processes. However,fortunately, our understanding of gender-specific differences in the initialpresentation, pathophysiology, treatment effectiveness, and clinical outcomes havechanged. The currently presented data are important to underscore the need to increaseknowledge about the importance of CAD in women, so that possible gender biases may beeffectively avoided, and better results obtained for the cardiovascular health ofwomen."} +{"text": "Sociedade Brasileira de Urolog\u00eda (SBU)) was founded in 1926 and in 1974 was launched the Brazilian Journal of Urology , a journal dedicated to publish the research from the Brazilian Urological community.The Brazilian Society of Urology , now a journal to where 2130 authors of 542 institutions from 62 countries have submitted 891 papers in the last 12 months.IBJU is an unique journal because it is an open-access journal which does not charge any fee for submission and/or publication; it is produced inside SBU headquarters and every expenses are supported by the society. Furthermore, it is possible to Brazilian and other Portuguese-speaking urologists to submit their papers in Portuguese and, once approved after peer-review, get a free English version..Luciano A. Favorito, MD, PhD was chosen to be the next Editor-In-Chief and we have been working together in the last two issues.I was elected as Editor-in-Chief in 2012 and this is my last issue since my term will end next December. Last August, 2019, It has been an honor to serve SBU and to conduct this very prestigious journal. It has been a great experience. During the last eight years IBJU's impact factor has risen, the review time has decreased significantly and the journal has attracted higher quality papers.Morais, Bruno A. Nogueira and Patricia Gomes.Editorial process is a team work and I need to thank the support of the successive SBU Board of Directors, to my Associate Editors and to the group responsible for our journal production: Ricardo de Finally, neither peer-review journal is produced without the reviewers; in 2019, 1536 reviewers helped us voluntarily to make an even better journal. As my last act I would like to announce the five most effective reviewers of 2019, based in their review quality, number and time length of review:Alexandre Danilovic, MD, Departamento de Urologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da USP, SP, Sao Paulo, Brasil; David Hernandez, MD, Department of Urology, University of South Florida, Tampa, FL, USA; Elcio Dias Silva, MD, Cl\u00ednica Dr. \u00c9lcio Dias Silva, Campinas, SP, Brasil; Hubert Swana, MD, Pediatric Urology, Nemours Children's Hospital Orlando, Orlando, FL, USA; Trushar Patel, MD, Department of Urology, University of South Florida, Tampa, FL, USA.See you."} +{"text": "Claude Martin, born in Boulogne-Billancourt, France, in 1949, died at North Hospital, Marseilles, France, on September 2, 2019. Claude qualified from the Marseille School of Medicine in 1979 and was appointed Professor of Anesthesiology and Intensive Care at South Hospital, Marseilles, in 1989. From 1992 to 2015, he chaired the Department of Anesthesiology and Intensive Care of the North Hospital, Marseilles. His life was dedicated to patient care, demanding the best for all patients admitted to our institution, allowing no concessions in terms of the services provided.Claude was an outstanding researcher, publishing his first peer-reviewed paper in 1987 , 3. He aCritical Care.Claude was a former president of the French Society of Anesthesiology and Intensive Care, as well as other national organizations. He was member of several international societies, chairing different sections and leading various projects within his fields of interest. He served as an editor for many journals, notably Outside his distinguished medical career, Claude was passionate about comics, rock music, and culture. His favorite pastime was traveling. He was a model of kindness, humanity, and humor and, despite repeated and ongoing health care problems, always continued his activities with a smile. He will be remembered by us all for his gentle elegance even in times of difficulty. During his final hours, Claude Martin was surrounded by his wonderful family."} +{"text": "It is vital to capture and analyze, from various sources in smart cities, the data that are beneficial in urban planning and decision making for governments and individuals. Urban policy makers can find a suitable solution for urban development by using the opportunities and capacities of big data, and by combining different heterogeneous data resources in smart cities. This paper presents data related to urban computing with an aim of assessing the knowledge that can be obtained through integration of multiple independent data sources in Smart Cities. The data contains multiple sources in the city of Aarhus, Denmark from August 1, 2014 to September 30, 2014. The sources include land use, waterways, water barriers, buildings, roads, amenities, POI, weather, traffic, pollution, and parking lot data. The published data in this paper is an extended version of the City Pulse project data to which additional data sources collected from online sources have been added. The data covers multiple sources in the city of Aarhus, Denmark. The sources are divided into two categories: static and dynamic. Static data sources present data related to land use, waterways, water barriers, buildings, roads, amenities, and POI. Dynamic data sources present weather, traffic, pollution, and parking lot data during the intended period. The association and structure of some data sources of the data are illustrated in The published data in this paper is an extended version of the City Pulse project data 22.1The study period was from August 1, 2014 to September 30, 2014, and took place at Aarhus, Denmark. Aarhus covers an area of 91 square kilometers and has a population of approximately 270,000 inhabitants. Some data sources, such as weather, land use, waterways, water barriers, buildings, roads, amenities, and POI were extracted, collected, and preprocessed from online sources. Moreover, the concentration of various pollutants, parking lots, as well as road traffic data, were taken from the City Pulse project using 217 sensors located in the city. 2.2To study and evaluate the system performance most researches related to urban computing applied a map splitting method and partitioned the evaluating data into segments according to fixed size grids or variable size regions. For the aim of this study, we follow such methods and published the data in this way. Therefore, the city is divided into segments according to one square meter grids and major roads. When the city is divided into one square meter grids, there are 620 grids that cover the whole city."} +{"text": "Scorpions are one of the most important venomous animals in Iran. Their sting has more prevalence in the south and southwest areas. The aim of this study was to introduce their sting agent species in the country.Data were extracted by a mini review on scorpion stinging articles in Iran until early 2018 and then the sting agent species in each area were studied. Geographical and provincial distribution of each species also was provided.Hemiscorpius lepturus, H. acanthocercus and Androctonus crassicauda. Remaining species have not deadly sting but because of their frequency, they encounter the individuals and cause the stinging.Twelve scorpion species are causative agents of sting. According to their deadly rate and clinical symptoms, some of them are considered the most dangerous venomous animals in Iran. Some death cases have been reported because of the sting of 3 species of The highest number of sting agents is in Khuzestan, however Gilan and Mazandaran have the lowest frequency. Because of the high prevalence of sting agent species in that province, the necessity of providing control and prevention programs is very important. Scorpion stinging has been reported in most of the warm areas of the world. These animals belong to the Arthropoda. Scorpion\u2019s geographic distribution is all over the world and the latitude between equator North 50 degree and south 52 degree but evenIn Iran, the species which sting humans are more opportunist in terms of habitat selection. They use ready spaces and gaps provided in the buildings because of using traditional building materials. This arthropod starts its activities at night and uses its venomous sting to defend or hunt insects to feed. The habitat of most of them is desert and non-residential places \u201314. SincScorpions are dangerous for humans because of having toxic and deadly sting and for this reason they are medically important so that according to the available statistics, they have the highest human casualties by venomous arthropod in the world , 18. TilSince many species live in Iran but sting of all of them has not been reported, the purpose of this study is introducing the sting agent species and determining their province distribution during the past 50 years in Iran.In this review article, keywords like scorpion, sting agents, dangerous species, provincial distribution, Iran, identification, studies, family and species were used in the sites related to valid medical and health journals, searching in databases like Web of Science, Ovid, PubMed, Systematic Review, SID, Iran Medex, Scirus, Google Scholar and Medline to have access to the articles during 1977 until early 2018. The including criteria for entry in this study articles were as follows, the first all Iranian articles about animal bites were searched. In the next step, they study focused on venomous animal bites and stings. Then the sting agents among of the scorpions were noticed, and then all articles of the scorpion sting agents in the past decades till now have been noticed. Overall, 150 sources were found, but only 75 of these considering the purpose of the study; i.e., report of the sting agent and concentration of study on Iran, 73 sources were surveyed. In addition to the survey of these studies, their application in Iran was done. Then the gained results were provided in tables, graph and figure.Up to now, three scorpion families have been reported in Iran. The sting agent scorpions in Iran include two families of Buthidae and Hemiscorpiidae. They have 12 species from the 8 genus which 10 species belong to Buthidae family and 2 species belong to Hemiscorpiidae family. More than 83.5% of the identified sting agent species in Iran belong to Buthidae family and 16.5% belong to Hemiscorpiidae family , 32, 33.Mesobuthus eupeus are in Ardabil, Kerman, Isfahan, Markazi, Mazandaran, Sistan and Baluchistan, Yazd, Kohgiluyeh and Boyer-Ahmad, Semnan, Fars, Khuzestan, Hormozgan, Golestan, Tehran, Kordistan, Kermanshah, Ilam, west Azarbaijan, Khorasan Razavi and Khorasan Jonoobi. Then, Compsobuthus matthiesseni in Bushehr, Chaharmahal and Bakhtiari, Fars, Hamadan, Kerman, Kohgiluyeh and Boyer-Ahmad, Kordistan, Lorestan, Markazi, Qom, Khuzestan, Hormozgan, Khorasan, Kermanshah, Ilam, west Azarbaijan and Isfahan, Hottentotta saulcyi in Lorestan, Hamadan, Chaharmahal and Bakhtiari, Khuzestan, west Azarbaijan, Kermanshah, Hormozgan, Ilam, Sistan and Balochistan, Kordestan, Kohgiluyeh and Boyer-Ahmad, Fars, Isfahan, Kerman and Ardabil, Odontobuthus doriae in Hormozgan, Kerman, Yazd, Isfahan, Markazi, Ghazvin, Tehran, Alborz, Semnan, west Azerbaijan, Kermanshah, Busher, Hamedan, Hormozgan, Hemiscorpius lepturus in Khuzestan, Semnan, Fars, Kordestan, Hormozgan, Bushehr, Ilam, Lorestan, Kermanshah, Isfahan, Hamedan, Kohgiluyeh and Boyer-Ahmad and Kerman, Orthochirus scrobiculosus in Khuzestan, Hormozgan, Tehran, Sistan and Balochestan, Qom, Isfahan, median (Razavi) Khorasan, Khorasan Jonobi, Gilan, Semnan, Kermanshah, Ilam, Androctonus crassicauda in Bushehr, Semnan, Khuzestan, Ilam, west Azarbaijan, Kordestan, Khorasan Razavi, south Khorasan, Kermanshah, Kerman and Sistan and Balochistan, Mesobuthus or Olivierus caucasicus in west Azarbaijan, Sistan and Balochestan, Isfahan, south Khorasan, Tehran, Markazi and Semnan, Hottentotta jayakari in Qom, Hormozgan and Fars, Hottentotta schach in Fars and Khuzestan, Hemiscorpius acanthocercus in Hormozgan and Apistobuthus pterygocercus in Khuzestan have been reported, respectively 50 is meaHemiscorpius genus includes dangerous and deadly species in the Middle East especially Iran and Iraq and are classified as the most deadly scorpions of the world (The number of scorpion species has been rapidly increasing in the last 3 decades in the world \u201361. The he world \u201371. At phe world \u201375.At present, the most dangerous species of scorpions are in the South and Southwest of Iran. However, completing the data about the sting agent scorpions\u2019 species in Iran needs more efforts of young researchers. Meanwhile, the completion of data in the field of Iran\u2019s sting agent scorpion species and different aspects of it needs cooperation between the physicians of the venomous animal\u2019s sting therapy units and the entomologist in this field. More accurate studies will be done with the cooperation of specialists of different fields about the sting agent species and the clinical effects of each species. This work necessitates a complete research in the country with a similar method and in the provinces and cities. Still, the highest species diversity is seen in the South and Southwest provinces but the diversity of scorpions in the Northeast and Northwest of Iran is less than the Southwest. In high-risk cities and villages, we recommend to the authorities of emergency department of hospitals and treatment centers, to emphasis on having scorpion sting agent by victim companions, because it helps to accurately identify sting agent."} +{"text": "European Congress of NeuroRehabilitation 2019 was held between 9 and 12 October in Budapest and benefited from participation of many neurologists, neurosurgeons, IT specialists, physiotherapists, occupational therapists, kinesiotherapists, logopedists, psychologists, medical assistants, psychiatrists, both from Romania and from abroad.Impairment, disability, handicap: So little done, so much to do\u201d.The central theme was \u201eSimilar to previous editions, the congress has maintained its international character, providing experts with a platform in all areas related to neurology and rehabilitation and hosting over 60 sessions with many international speakers -5.The Organizing Committee of the event included personalities such as: Dafin Muresanu \u2013 President, Volker Homberg \u2013 Program President, Leopold Saltuari, Giorgio Sandrini, Heinrich Biner and Karin Diserens.The event was organized in collaboration with the Bulgarian Society of NeuroRehabilitation, European Academy for Neurology, Romanian Society for Neuropsychological and Motor Rehabilitation, Romanian Society for NeuroRehabilitation, etc.theory and research, evidence based on effectiveness and safety, international validation of the obtained results. He also mentioned the need to develop guides in partnership with the societies in the field and to implement them in the EFNR member societies.In the opening of the congress, Prof. Dafin Muresanu, MD, PhD, approached the subject of changing the philosophy in neurorehabilitation, referring to the three basic pillars: The aim of the congress was to keep the dialogue open between the countries of Europe but also with colleagues in the field, from all over the world.As it is well known, the goal of all neurologists is continuous research, collaboration in order to avoid damage and disability because of brain and cardiovascular diseases, accidents and injuries or functional disorders.Among the novelties of the event were the following: interactive teaching day dedicated to young researchers who took part in the congress; \u201eAsk the expert!\u201d breakfast sessions, in which 10 professors offered their experience, advice and knowledge in two parallel 60-minutes morning sessions; career development, which implied the improvement of knowledge on how to organize a study, how to best write an academic paper, and also how to choose the career path; young experts\u2019 battle, in which young specialists, aged below 35 years, participated in debates that also involved the audience; best oral presentations, implied the presentation of the six best rated abstracts that were presented in 30-minutes lectures.Moreover, among the key topics of the congress were the following: \u201cImpairment vs. compensation oriented approaches in stroke \u2013 when to switch\u201d, \u201cNew vistas for education in neurorehabilitation in Europe\u201d, \u201cThe enigma of \u201cproportional recovery\u201d \u2013 impact for neurorehabilitation\u201d, \u201cInnovative strategies for neurorehabilitation trials\u201d, \u201cThe rationales of cognitive training strategies\u201d."} +{"text": "In this data article, a thorough dataset on patterns of electricity use in Nigerian public universities was presented. Three relatively old public universities with staff and students\u2019 halls of residences were purposively selected. The selected universities were Obafemi Awolowo University, Ile-Ife (OAU), Federal University of Technology, Akure (FUTA), and University of Ibadan (UI). Data were obtained through the administration of a structured questionnaire on electricity end users in the universities sampled. For the data collection, the electricity end users in public universities were stratified into users in university staff offices, staff residences, student residences, and commercial units. Electricity users were selected using systematic random sampling and accidental sampling techniques. In OAU, FUTA and UI, 217, 137 and 164 students, respectively were sampled; 30, 3, and 61 households in OAU, FUTA, and UI, respectively were sampled while 28, 6, and 18 commercial units in OAU, FUTA and UI, respectively were also sampled. The sample size determined for staff in OAU, FUTA and UI were 139, 81 and 182, respectively. The data obtained were analyzed using radar charts. The information provided in this data article will encourage investigation into electricity management strategies, critical success factors for electricity management, planning, and policy formulation towards the realization of sustainable campuses. Specification tableValue of the data\u2022The data will foster more empirical investigation for a better understanding of areas of improvement in electricity use \u2022The data provided in this article is useful for the development of electricity use models, energy audit, and energy management practices \u2022The data provided will assist the government and the management of public universities in result-oriented planning, budgeting, and decision-making \u2022The provision of this data will propel the achievement of the sustainable campus environment 1The patterns of electricity consumption were demonstrated from different perspectives , Fig. 8.2The quantitative technique was adopted. The instrument for data collection was a structured questionnaire. A multi-stage sampling technique was used for the data collection The populations of students occupying these hostels earlier determined were 1228, 1200 and 1618 for Moremi, Jadesola Akande and Awolowo halls, respectively; 2,032, 1142 and 956 for Awolowo, Peter Adeniyi and Independence halls, respectively, while there were 1072 , 400 and 700 in Murtala Muhammed, FUTA and Abdusalam Abubakar Postgraduate halls, respectively. One out of every twenty (5%) students were selected in each hall. In all, 217, 137 and 164 students were sampled in OAU, FUTA, and UI, respectively. The preliminary investigation also showed that in OAU, FUTA, and UI, there were 600, 50 and 1212 households, respectively in staff residential quarters while there were 552, 115 and 350 shops, respectively to constitute the sample frame for both staff housing units and business units. One out of every twenty (5%) households and shops were selected. Using this method, 30, 3 and 61 households in OAU, FUTA, and UI, respectively were sampled while 28, 6 and 18 business units in OAU, FUTA, and UI, respectively were also sampled. For staff offices, accidental sampling was used across academic, administrative and other cadres of staff in the three universities. The sample size determined for staff in OAU, FUTA and UI were 139, 81 and 182, respectively.The amount of electricity consumption was calculated from Eq."} +{"text": "After publication of this article, the authors became aware of an error in the quoted number of philosophical-belief vaccine nonmedical exemptions (NMEs) in Allegheny County, Pennsylvania. The quoted number of 424 exemptions resulted from an inadvertent doubling of the correct number of 212. The authors apologize for this error. All the data and analyses in the paper have now been thoroughly checked, and we can verify that, while the error affected all entries in the Pennsylvania county-level dataset, no data from other states were affected. Therefore, the authors would like to correct the text and figures of the article as follows, to remove Allegheny County from the maps and rankings of areas with >400 kindergarteners with NMEs in 2016-2017. In addition to Allegheny County, NME rates for all counties in Pennsylvania have been corrected in There were also two minor errors in presentation that need to be corrected, regarding the list of states in the second summary point and an asterisk missing from The first sentence of the second Summary point should read \u201cSince 2009, the number of philosophical-belief vaccine nonmedical exemptions (NMEs) has risen in 12 of the 18 states that currently allow this policy: Arizona (AZ), Arkansas (AR), Idaho (ID), Maine (ME), Minnesota (MN), Missouri (MO), North Dakota (ND), Ohio (OH), Oklahoma (OK), Oregon (OR), Texas (TX), and Utah (UT).\u201dWe would also like to amend the third Summary point, to substitute the names of the counties from which data were derived for the names of cities within those counties. The first sentence of the third Summary point should read \u201cSeveral US \u201chotspot\u201d metropolitan areas stand out for their very large numbers of NMEs. They include King County, WA, Spokane County, WA, and Multnomah County, OR, in the Northwest; Maricopa County, AZ, Salt Lake County, UT, Utah County, UT, Harris County, TX, Tarrant County, TX, Collin County, TX, and Travis County, TX, in the Southwest; and Oakland County, MI, Macomb County, MI, Wayne County, MI, and Jackson County, MO, in the Midwest.\u201dThe third paragraph of the section subtitled \u201cGoing granular\u201d should read \u201cFurthermore, we examined total numbers of kindergarteners with NMEs per county to identify focal areas with large numbers of potentially vulnerable pediatric populations. County NME totals were also provided by state health departments. The exception is MO, whose private kindergarten (2015\u20132016) and public kindergarten (2014\u20132015) enrollment numbers were taken together from the National Center for Education Statistics (nces.ed.gov) to derive NME raw counts. Shown in In The penultimate line in the second paragraph of the Discussion should be \u201cOur analysis identified the following hotspot metropolitan areas: Seattle, WA, Spokane, WA, and Portland, OR in the Northwest; Phoenix, AZ, Salt Lake City, UT, Provo, UT, Houston, TX, Fort Worth, TX, Plano, TX, and Austin, TX in the Southwest; Troy, MI, Warren, MI, Detroit, MI, and Kansas City, MO in the Midwest.\u201dThe Acknowledgments should read: We would like to acknowledge the following state health departments that provided us with data wherever possible: AR Department of Health, ID Department of Health and Welfare, LA Department of Health, MO Department of Health and Senior Services, ND Department of Health, OR Health Authority, TX Department of State Health Services, UT Department of Health, and WI Department of Health Services."} +{"text": "Peterson discusses five principles that are used in the ethics of technology.He analyzes these principles by means of the mathematical theory of Voronoi regions. The concept of a Voronoi region is a simple but intuitively appealing one. Given a finite set of distinct, isolated points in a continuous space, we associate all locations in that space with the closest member of the point set. The result is a partitioning of the space into a set of Voronoi regions. The mathematical theory of Voronoi regions has successfully been applied in many areas, including philosophy . Its application to the ethics of technology seems new.However, Peterson\u2019s book raises several problems.https://www.virtuescience.com/the-virtues.html, namely, acceptance, accountability, ambition, assertiveness, beauty, benevolence, bravery, caring, charity, chastity, caution, cleanliness, commitment, compassion, confidence, consideration, contentment, cooperation, courage, courtesy, creativity, curiosity, defiance, dependability, detachment, determination, devotion, diligence, discernment, discretion, discipline, eloquence, empathy, enthusiasm, excellence, faith, faithfulness, flexibility, focus, forbearance, forgiveness, fortitude, friendliness, frugality, generosity, gentleness, grace, gratitude, helpfulness, honesty, honor, hope, humbleness, humility, humor, idealism, integrity, impartiality, industry, innocence, joyfulness, justice, kindness, knowledge, liberality, love, loyalty, magnanimity, majesty, meekness, mercy, moderation, modesty, obedience, openness, orderliness, patience, peace, perseverance, persistence, piety, prudence, punctuality, purity, purposefulness, reliability, resoluteness, resourcefulness, respect, responsibility, restraint, reverence, righteousness, selflessness, self-sacrifice, service, sensitivity, silence, simplicity, sincerity, sobriety, spontaneity, steadfastness, strength, tact, temperance, thankfulness, thrift, tolerance, toughness, tranquility, trust, trustworthiness, truthfulness, understanding, unity, vitality, wisdom, wonder and zeal?First, in his book, \u201cclosest\u201d means \u201cmost similar in a moral sense.\u201d But how is \u201cmost similar in a moral sense\u201d to be understood? As most similar with respect to what? As most similar with respect to catastrophic consequences? As most similar with respect to fairness? Or as most similar with respect to one of the traditional virtues mentioned at Notre Dame Philosophical Reviews, 2017.10.30):Without pre-specified moral-similarity dimensions, each agent likely employs her own implicit dimension(s) to answer Peterson\u2019s moral-similarity request. Thus for the same two cases, one agent might estimate \u201cmoral similarity\u201d with respect to catastrophic consequences, while another might estimate similarity with respect to fairness. If so, Peterson has a common moral-similarity label, but no common concept.Second, Peterson\u2019s geometric construal of domain-specific principles is unclear. He writes (p.\u00a019):We start with intuitions about a set of nonparadigmatic cases we feel reasonably certain about. The next step is to identify the principles that best account for our intuitions about these cases. Once we have done so, we determine the location of the paradigm cases for these principles ex-post by calculating the mean coordinates of the nonparadigmatic cases we started with.But he then goes on as follows (p.\u00a019):Step 1C in which there is no or negligible doubt about what ought to be done and why.Identify a nonempty set of paradigm cases Step 2c in C, identify the principle p that best accounts for the moral analysis of c. Let P be the set of all such principles.For each case Step 3C, with respect to how similar they are to each other.Compare all cases, including those not included in Step 4p in P. Each cell of the Voronoi tessellation represents the case covered by p, and it is thus the degree of similarity to nearby paradigm cases that determines what it is right or wrong to do in each and every case.Make a Voronoi tessellation in which each seed point is a paradigm case for some principle To reconcile these two quotes, \u201cnonparadigmatic\u201d in the first quote should be replaced by \u201cparadigmatic.\u201dAs Kristin Shrader\u2013Frechette writes (five principles? If five principles partition the moral space into a set of Voronoi regions, then four or six obviously do as well. Why these five principles? Why is the maximin principle, for example, not included? Why does Peterson not use some familiar statistical technique, such as factor analysis or principal component analysis, to find out which principles matter?Third, Peterson repeatedly claims that his five principles \u201care necessary and jointly sufficient for analyzing ethical issues related to new and existing technologies,\u201d but he offers no proof of this claim. Why https://www.virtuescience.com/the-virtues.html shows that they are neither necessary nor sufficient. If somebody left out a principle or added one, then Peterson\u2019s geometric construal would still work, so nothing depends on his claim.To me, Peterson\u2019s five principles seem no more than a list of topics that are currently fashionable in the ethics of engineering and that are well-known to students of that field. The list of virtues mentioned at"} +{"text": "The Medical Library Association (MLA) held its 119th annual meeting in Chicago, Illinois, May 3\u20138, 2019, at the Hyatt Regency Chicago. The meeting theme was \u201cElevate.\u201d Total attendance for the meeting was 1,661, with 228 participating in continuing education courses. Additional meeting content\u2014including the meeting program and various electronic presentations from the business meetings, plenary sessions, poster sessions, and program sessions\u2014can be accessed by all meeting registrants via the MLA \u201819 website.Executive Director Kevin Baliozian welcomed attendees and then introduced MLA President Beverly Murphy AHIP, FMLA. President Murphy welcomed attendees to the 2019 annual meeting.President Murphy then introduced Merle Rosenzweig, who welcomed attendees on behalf of the Midwest Chapter.Merle Rosenzweig: I want to thank Beverly again. And she has been practicing my last name for a long time, and she did it! So, to everyone here, all the MLA members, the Midwest Chapter of the Medical Library Association welcomes you to the 2019 annual meeting. The chapter was founded in 1950 and includes the great states of Illinois, Indiana, Iowa, Kentucky, Michigan, Minnesota, North Dakota, Ohio, and Wisconsin.A little history of the chapter: During the World War II years, MLA could not have its meetings, and some of the regional groups continued to have their meetings. When Janet Doe was president, a committee was formed to set up guidelines for regional groups, and the committee was chaired by Margueriete Prime. And anyone who knows Margueriete Prime has been here longer than I have. And they recommended the establishment of regional groups and presented a set of guidelines to be observed.So, with our annual meeting of the Midwest Chapter, we stimulate and foster an interest in health sciences libraries and librarianship, and acquaint persons interested in health sciences libraries and librarianship with MLA. All of the chapters are part of MLA, obviously, and we do promote MLA.The Midwest Chapter hopes that you have a very productive meeting here in Chicago in 2019 and have the opportunity to see some of the sights, sounds, and food that Chicago has to offer.Applause.]So that is my short speech, and now it\u2019s my pleasure to introduce a group of very creative people who made this great meeting here in Chicago possible. They will come on stage now. Dale Prince: On this first day of Ramadan\u2014and Mellanye Lackey: But you can Google them.Dale Prince: Librarians. So we\u2019ve borrowed this for our theme, Elevate. It\u2019s awe-inspiring. It\u2019s about movement, just like libraries, librarianship, and librarians. And like the L, we hope the programming of this year\u2019s meeting will elevate you and take you to places you want to be.Mellanye Lackey: Some of the new things in this year\u2019s meeting include an option to list your chosen pronouns during registration and have them printed on your badge; immersion sessions with surveys to collect immediate feedback; this year\u2019s service project, Sit, Stay, Read, which brings human and dog volunteers into low-income Chicago public schools to advance children\u2019s literacy. MLA members, you all have already contributed $500 to buy books for kids to read to dogs. Thank you for your generosity. Visit their booth today from 1:00 p.m. to 3:00 p.m. and tomorrow from noon to 2:00 p.m. at the escalator above the exhibit hall, right by registration, to see more of the adorable dogs and to learn more about their work.Applause.]Dale and I would also like to recognize members of the NPC who have put in countless hours of service to MLA to make this meeting a success. They have worked so hard to create an excellent program to inspire us and to elevate us. If the members of the NPC could please rise and be recognized. Rosie Hannneke: We\u2019re so glad you made it to Chicago to elevate with us. We hope you will enjoy our beautiful and vibrant city while you\u2019re here. From museums and shopping to dining to simply taking in the sights and sounds of the Loop, there are so many ways for you to spend your free time both here, downtown, and farther afield. And those of you who were lucky enough to get tickets to Deb Werner: Stop by the hospitality desk just outside the ballroom for more information about the Windy City. We\u2019ve got directions, whether you\u2019re going near or far, from maps of the pedway in this hotel to public transportation information if you\u2019d like to explore one of Chicago\u2019s seventy-seven unique neighborhoods. Be sure to pick up a bingo card courtesy of Sola Whitehead and Chris Shaffer, AHIP, and use it to meet new people.This year, in partnership with many MLA chapters, we included dine-arounds on Friday and some on Monday as well, so if you attended one of these chapter dinners or happy hours, please let us know what you think of this addition.Rosie Hanneke: We\u2019d like to thank the LAC subcommittee chairs who worked behind the scenes to make this meeting a success. We\u2019d also like to thank everyone else who volunteered their time to stuff meeting bags, host dine-arounds, staff the hospitality desk or career placement center, or help in any other way\u2014all important and needed contributions. If you\u2019re a subcommittee chair or volunteered in any capacity for the LAC, could you please stand so we can give you a hand. [Applause.]Applause.]Deb Werner: Thank you, everyone, and welcome, all of you, to Chicago, have a great meeting, and we\u2019re so glad you\u2019re here. Thank you. We adapted, we transformed, and led, and it just got better from there.We have all moved from where we were last year to another space in time. So, what did I do in elevating my platform this past year? My presidential year actually started in May 2018 at the annual meeting in Atlanta\u2014the home of Coke, grits, pie, and fried foods\u2014when I was inaugurated as the first African-American president of our beloved association. Since there are more chapters than I could possibly attend, I give a big thanks to my cohorts and partners. Past President Epstein presented at the Hawaii-Pacific Chapter, New York-New Jersey Chapter, and Pacific Northwest Chapter. President-Elect Julia Esparza, AHIP, presented at the North Atlantic Health Sciences Libraries (NAHSL) in New Hampshire and was a librarian on a mission at the South Central Chapter in San Antonio, Texas. Treasurer-Elect Shannon D. Jones, AHIP, experienced the magic in Orlando, Flortida, with the Southern Chapter. And Marie T. Ascher presented at the Philadelphia Regional Chapter and crossed borders and broke boundaries at Upstate New York and Ontario Chapter (UNYOC) in Niagara-on-the-Lake, Ontario, Canada. [Applause.]In June, I will be part of a panel at the Northern California and Nevada Medical Library Group and the Medical Library Group of Southern California and Arizona joint meeting on critical health sciences librarianship examining our role in social justice. So, remember, over the next year, remain calm, remain open, remain flexible, and remain positive. Leverage what you know, recognize what you don\u2019t know, and fill in the gaps with chocolate. [Applause.] My posse\u2014you all know who you are\u2014the medical center library and archive staff, which is where I work. Thank you so much. MLA headquarters staff, we couldn\u2019t do it without you. You\u2019re just fantastic people to work with, and I\u2019ve worked with you a very long time, and you just get better every year, so thank you.So, in addition to thanking my mentors, there are many others to thank, but I\u2019d like to recognize a few now. My sugar, honey, darling, baby, sweetheart, Jerome Ballew. He is here today. Jerome, raise your hand. Thank you. Thanks, everyone.So, last year, we anticipated a revenue of $1,837, but we actually finished with $15,315. That, I\u2019m told, is a 12% increase in actual revenue; $14,000 above budget. I\u2019ll leave you guys with an image of Cujo ordering things from Amazon, and Cooper just living his best life. I hope that Shannon Jones includes lots of pictures of Cooper in the future in our slides. Thank you, everyone. [Applause.]So, that\u2019s the end of my treasurer\u2019s report. Kevin Baliozian: Thank you very much, Beverly Murphy. Shannon Jones and I already have one major connection. I have a dog called Cooper, so it\u2019s very exciting. Now, every time you see the boxes go up, I\u2019d like you to say, \u201cElevate,\u201d because this is the next few slides. Member engagement: there will be a few slides on this. This is a really exciting story here. We have 627 of you members participating in MLA committees and juries. That does not count section roles, special interest group (SIG) roles, chapter roles. That\u2019s 24% of the association just in committees, task forces, and juries. That\u2019s phenomenal. [To Beverly Murphy:] You said so many times, if you don\u2019t apply, you can\u2019t get on a committee. And how many times did you say this?And the graph below is the number of people applying to be volunteers, and look at this: from 167 to 272. So, yes, our membership has gone down during that time, and the number of you engaged has gone up. This is phenomenal, and you are a big part of it. Thank you very much.That\u2019s it. I am sure almost everyone has at some point seen a roll of pennies. I want you to think of this roll of pennies as MLA. When we open this roll, we know what is inside: fifty pennies. Now, these individual pennies are the valuable members who make up MLA. They are not all identical, but they are all important parts of the whole.Julia Esparza, AHIP: Thank you, Beverly. I appreciate that wonderful introduction. Today, I would like to talk with you about how MLA is in the process of elevating our vision. First of all, who can tell me what this is? Hey, I know these people. [Laughter.] And section treasuries are depleting. Sections are spending beyond what the dues bring in.Section membership numbers are declining, and yes, this is\u2014because these are data from before Kevin Baliozian presented his today, so don\u2019t hold it against me on Twitter. While this may seem messy and noisy, this is part of growth.And all of this together will help MLA to become a more nimble organization responsive to the needs of its members. In order to do this, we had to break our barriers. [Applause.]Caucuses will have the flexibility to align with the domains that are relevant to the needs of their members. Caucuses within domains can work together. While this has been an established part of annual meeting planning, now this collaboration can go beyond annual meetings to projects and initiatives that may not have easily happened in the old organization. The organization may change and is meant to change as members express their ideas as to what is important to them. But the important thing to remember is that no matter how caucuses align, we will still add up to the whole. Thank you, everyone.I thank you, MLA, for giving me this opportunity to serve as your president. I know that the future isn\u2019t always clear; however, I know that together, we will do everything we can to make the future of MLA fantastic. Thank you. [Get on board and join us for the hottest ticket at the Chi-Town networking event tonight, where you will enjoy a great dinner and be entertained by your colleagues at the open mic night.This session is now closed.Journal of the Medical Library Association.Breakout sessions for immersion sessions, lightning talks, and paper sessions were presented in 6 time slots: Sunday, May 5, 2:00 p.m.\u20133:25 p.m. and 4:30 p.m.\u20135:55 p.m.; Monday, May 6, 2:00 p.m.\u20133:25 p.m. and 4:30 p.m.\u20135:55 p.m.; and Tuesday, May 7, 2:00 p.m.\u20133:25 p.m. and 4:30 p.m.\u20135:55 p.m. Abstracts of papers that were scheduled to be presented are available on the MLA \u201819 website. The final version of the abstracts reflecting only those presented at the meeting is included as Journal of the Medical Library Association. The actual posters are available online in the MLA \u201819 meeting website.Poster sessions were presented in 3 time slots: Sunday, May 5, 3:30 p.m.\u20134:25 p.m.; Monday, May 6, 3:30 p.m.\u20134:25 p.m.; and Tuesday, May 7, 3:30\u20134:25 p.m. Abstracts of posters that were scheduled to be presented are available on the MLA \u201819 meeting website. The final version of the abstracts reflecting only those posters presented at the meeting is included as an The MLA Board of Directors met on Thursday, May 2, and Friday, May 3. The Credentialing Committee met on Friday, May 3. On Saturday, May 4, the following MLA units met: 2020 National Program Committee, Chapter Council, Department of Veteran Affairs Librarians SIG Business Meeting, Eugene Garfield Research Fellowship Jury, Joint Section Council/Chapter Council, Leaders\u2019 Recognition Reception, and Section Council.Journal of the Medical Library Association (JMLA) Editorial Board Meeting, LGBTQ Health Sciences Librarians SIG Business Meeting, Medical Humanities SIG Business Meeting, Medical Informatics Section Business Meeting, Medical Library Education Section (MLES) Business Meeting, Medical Library Group of Southern California and Arizona Business Meeting, MLA Book Discussion Group for Blindspot, New York-New Jersey Chapter Board Meeting, Nursing and Allied Health Resources Section (NAHRS) Business Meeting and Executive Board Meeting, Public Health/Health Administration Section Business Meeting, Research and Evidence-Based Practice Curriculum Committee Meeting, Research Section Research Award Judging Meeting, Resource Sharing SIG Business Meeting, Rising Stars Program Meeting, Social Justice Section Business Meeting, and Southern Chapter Executive Meeting.On Sunday, May 5, the following MLA units met: Ad Hoc Committee to Review Core Clinical Journals, African American Medical Library Alliance SIG Business Meeting #1, chapter treasurers orientation, Data Catalog Collaboration Project information session, education committee chairs joint meeting, Fellows of MLA, History of the Health Sciences Section Business Meeting, International Cooperation Section Business Meeting, On Monday, May 6, the following MLA units met: 2021 National Program Committee Meeting, African American Medical Library Alliance SIG Business Meeting #2, Awards Committee Meeting, Books Panel Meeting, Cancer Librarians Section Business Meeting, Collection Development Section Business Meeting, Complementary and Alternative Medicine SIG Business Meeting, Consumer and Patient Health Information Section (CAPHIS) Executive Committee Meeting, Data SIG Business Meeting, Dental Section Business Meeting, Educational Media and Technologies Section (EMTS) Business Meeting, Federal Libraries Section Business Meeting, Governmental Relations Committee Meeting, Health Association and Corporate Libraries Section (HACLS) Business Meeting, Health Information Professionalism Curriculum Committee Meeting, Hospital Libraries Section (HLS) Executive Board Meeting and Business Meeting, Information Literacy in Medical Education (ILME) SIG Business Meeting, Information Services Curriculum Committee Meeting, Instruction and Instructional Design Committee Meeting, Librarians without Borders\u00ae Committee Meeting, Libraries in Curriculum SIG Business Meeting, Molecular Biology and Genomics SIG Business Meeting, Northern California and Nevada Medical Library Group Business Meeting, Osteopathic Libraries SIG Business Meeting, Pacific Northwest Chapter Business Meeting, Pediatric Librarians SIG Business Meeting, Pharmacy and Drug Information (PDI) Section Business Meeting, Professional Recruitment and Retention Committee Meeting, Public Services Section Business Meeting, Scholarly Communications Committee Meeting, Solo Librarians SIG Business Meeting/Chat, Systematic Reviews SIG Business Meeting, Technical Services Section Business Meeting, Translational Sciences Collaboration SIG Business Meeting, Veterinary Medical Libraries Section Informal Meeting, and Vision Science SIG Business Meeting.Journal of the Medical Library Association (JMLA) data sharing policy: author discussion and preparation, Latino SIG Business Meeting, Leadership and Management Section Business Meeting, Leadership & Management Curriculum Committee Meeting, Joseph Leiter NLM/MLA Lectureship Committee Meeting, Membership Committee Meeting, MLA community managers and webmasters, MLAConnect Editorial Board Meeting, Research Section Business Meeting, Rising Stars presentations, section treasurers orientation, and Systematic Reviews SIG Informal Meeting.On Tuesday, May 7, the following MLA units met: Bylaws Committee Meeting, Clinical Librarians and Evidence-Based Healthcare SIG Business Meeting, Consumer and Patient Health Information Section (CAPHIS) Business Meeting, Diversity and Inclusion Task Force Meeting, Education Steering Committee Meeting, Information Management Curriculum Committee Meeting, Institutional Animal Care and Use SIG Business Meeting, Interprofessional Education SIG Business Meeting, On Wednesday, May 8, the following MLA units met: Education Annual Programming Committee (EAPC) Meeting, Grants and Scholarships Committee Meeting, and Oral History Committee Meeting.The MLA Open Forum was held on Monday, May 6, 10:30 a.m.\u201311:55 a.m.The National Library of Medicine (NLM) Update took place on Tuesday, May 7, 11:00 a.m.\u201311:55 a.m.The Legislative Update was held on Tuesday, May 7, from 2:00 p.m.\u20133:25 p.m. Moderated by Cristina Pope, this update provided an overview of health funding, information issues, and policy.National Network of Libraries of Medicine (NNLM) Steering Committee Annual Meeting (invitation only), 2:00 p.m.\u20134:00 p.m.Welcome Reception and Opening of the Hall of Exhibits, 5:00 p.m.\u20137:30 p.m.MLA New Members/First-Time Attendees Program and Breakfast, 7:00 a.m.\u20138:55 a.m.Yoga Class, 7:30 a.m.\u20138:30 a.m.Covidence Library Champions (invitation only), 8:00 a.m.\u20138:55 a.m.DOCLINE Users Group, noon\u201312:55 p.m.Librarians without Borders\u00ae/Elsevier Foundation Research4Life Grants: Round Table Discussion, noon\u201312:55 p.m.Elevate Your Practice with Research: Research Training Institute (RTI) Fellows and Faculty Share Their Experience Designing and Conducting Research, 1:00 p.m.\u20131:55 p.m.Association of Academic Health Sciences Libraries (AAHSL) Future Leadership Committee Meeting (invitation only), 1:00 p.m.\u20131:55 p.m.PubMed Update, 1:00 p.m.\u20131:55 p.m.International Visitors Reception, 7:00 p.m.\u20138:00 p.m.Schmooze with Science (invitation only), 7:30 p.m.\u20139:00 p.m.AAHSL/NLM Fellowship Program Information Session, noon\u201312:55 p.m.Covidence Advisory Group Meeting (invitation only), noon\u201312:55 p.m.Lunch & Learn: Best Practices: Implementation and Rollout of Ovid Discovery (invitation only), noon\u20131:00 p.m.Lunch & Learn: One-Click Access to PDFs from PubMed: Using the New LibKey Service from Third Iron, noon\u20131:00 p.m.Academy of Health Information Professionals Q&A Session, 1:00 p.m.\u20131:55 p.m.Diversity Dialogues with the Diversity and Inclusion Task Force, 6:00 p.m.\u20137:30 p.m.Lunch & Learn: Elsevier Luncheon for Medical Librarians (invitation only), noon\u20131:55 p.m.MLA Book Authors and Prospective Authors Gathering, 3:30 p.m.\u20134:25 p.m.Get on Board: Hottest Ticket in Chi-Town Networking Event, 6:30 p.m.\u201310:00 p.m.Invitation to MLA \u201820 in Portland, 10:00 a.m.\u201310:15 a.m.Book Sales and Signings, noon\u201312:30 p.m.Exhibitors held Sunrise Seminars to provide information and to introduce new products and services. The following seminars were held.EBSCO Health: Beyond Evidence on Fast Healthcare Interoperability Resources (FHIR)Elsevier: Defining a \u201cPreprint\u201dSpringer Nature: Copyright Compliance for Commercial Use: Identify, Educate, and LicenseWolters Kluwer: Information Overload: An Opportunity for Library Service Development (invitation only)American Psychological Association (APA) Sunrise SeminarEBSCO Health: A Total Transformation: How One Medical Library Took Charge of Their Physical and Digital SpaceVisualDx: Connecting Symptoms to Construct a DiagnosisSix Technology Showcases were held throughout Sunday, Monday, and Tuesday.EndNote: More than Just a Reference ManagerImplement a Systematic Review Management System with CovidenceMore than Just Reference Management: How DistillerSR and CuratorCR Can Make Your Job EasierOpenAthens: The Authentication LandscapeThe R2 Digital Library: A Health Sciences E-Book DatabaseStanding Out from the Crowd: A New, Multidimensional Approach to Researcher ProfilesThe 2018/19 Continuing Education Committee offered the following courses to 228 attendees on May 3 and May 4, 2019.CE100 Advanced Searching Techniques and Advanced Strategy Design, Instructors: Julie Glanville, MCLIP, associate director, York Health Economics Consortium, University of York, York, United Kingdom, and Carol Lefebvre, HonFCLIP, independent information consultant, Lefebvre Associates, Oxford, United KingdomCE101 Fields, Filters, and Fun: Incorporating Creativity and Craft into Database Literature Searches, Instructors: David Kaunelis, methods specialist, and Kelly Farrah, AHIP, research information specialist, Research Information Services, Canadian Agency for Drugs and Technologies in Health (CADTH), Ottawa, ON, CanadaCE102 Health Services Research: Sources and Strategies for Effective Information Searching, Instructors: Judith E. Smith, informationist, Taubman Health Sciences Library, University of Michigan\u2013Ann Arbor, and Abraham Wheeler, AHIP, librarian, College of Osteopathic Medicine, Flint Research, and Department of Epidemiology and Biostatistics, Michigan State University\u2013East LansingCE300 Developing Library Data Visualization Services from Scratch, Instructor: Fred Willie Zametkin LaPolla, research and data librarian, Health Sciences Library, New York University (NYU) Langone\u2013New YorkCE301 Applying the ACRL Information Literacy Framework to Your Teaching, Instructors: Xan Goodman, AHIP, health sciences librarian and associate professor, and Samantha Godbey, education and psychology librarian and associate professor, University Libraries, University of Nevada\u2013Las VegasCE103 Effectiveness and Efficiency in Exhaustive Searches, Instructors: Wichor M. Bramer, biomedical information specialist, Medical Library, Erasmus University Medical Center, Rotterdam, The Netherlands, and Melissa L. Rethlefsen, AHIP, associate dean, George A. Smathers Libraries, and Fackler Director, Health Science Center Libraries, University of Florida\u2013GainesvilleCE104 Which Review Is Right for You? Matching Questions to Review Type and Teaching the Process to Others, Instructor: Margaret J. Foster, systematic reviews and research coordinator, Medical Sciences Library, Texas A&M University\u2013College StationCE105 We\u2019re Way Past Peas: Uses of Genetic Information to Understand Human Health and Guide Health Care Decision Making, Instructors: Diana Nelson Louden, biomedical and translational sciences librarian, Health Sciences Library, University of Washington\u2013Seattle, and Carolyn Martin, AHIP, consumer health coordinator, National Network of Libraries of Medicine, Pacific Northwest Region, Seattle, WACE106 Trials without Tribulations: Identifying Clinical Trials for Systematic Reviews and Other Clinical and Research Questions, Instructors: Julie Glanville, MCLIP, associate director, York Health Economics Consortium, University of York, York, United Kingdom, and Carol Lefebvre, HonFCLIP, independent information consultant, Lefebvre Associates, Oxford, United KingdomCE107 Going for the Grey: Finding Grey Literature for Complex Reviews, Instructors: Sarah Bonato, reference/research librarian, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; and Kelly Farrah, AHIP, research information specialist, and Monika Mierzwinski-Urban, research information specialist, Research Information Services, Canadian Agency for Drugs and Technologies in Health (CADTH), Ottawa, ON, CanadaCE302 Teaching Critical Appraisal Skills, Instructor: Laura Menard, assistant director, Medical Education and Access Services, Ruth Lilly Medical Library, Indiana University\u2013IndianapolisCE400 Implicit Bias Training for Information Professionals, Instructors: Shannon D. Jones, AHIP, director, Libraries, and associate professor, Medical University of South Carolina\u2013Charleston; and Kelsa Bartley, manager, Library Services, Reference and Education Department, Louis Calder Memorial Library, and Kimberly L. Reynolds, assistant professor, Clinical Pediatrics, University of Miami Miller School of Medicine, Miami, FLCE501 Beyond Pyramids of Evidence: Evaluating Research in the Health Sciences Literature, Instructors: Abraham Wheeler, AHIP, librarian, College of Osteopathic Medicine, Flint Research, and Department of Epidemiology and Biostatistics; Chana Kraus-Friedberg, AHIP, liaison, Program in Public Health, Department of Pharmacology and Toxicology; and Carin Graves, liaison librarian, Sociology, Social Work, Criminal Justice, and Human Development and Family Studies; Michigan State University\u2013East LansingCE502 Advancing Health Equity through Evidence-Based Public Health: How to Find the Evidence, Instructors: Elaina Vitale, academic coordinator, National Network of Libraries of Medicine, Middle Atlantic Region, Pittsburgh, PA, and Derek Johnson, health professionals outreach specialist, National Network of Libraries of Medicine, Greater Midwest Region, Hardin Library for the Health Sciences, University of Iowa\u2013Iowa CityCE601 Institutional Review Boards (IRBs): Integrating Information Professionals into the Process, Instructors: Taneya Y. Koonce, associate director, Research; Sheila V. Kusnoor, senior research information scientist; Zachary E. Fox, associate director, Information Services; Annette M. Williams, senior information scientist; and Mallory N. Blasingame, information scientist; Center for Knowledge Management, Vanderbilt University Medical Center, Nashville, TNCE602 Goal: Success at Being a Solo Librarian!, Instructors: Helen-Ann Brown Epstein, AHIP, FMLA, informationist, Health Sciences Library, Virtua Health, Mount Laurel, NJ, and Louise McLaughlin, information specialist, Health Sciences Library, Woman\u2019s Hospital, Baton Rouge, LACE800 Managing from the Middle: Learning to Lead from Where You Are, Panelists: Joan Gallos, professor of leadership emerita, Wheelock College, Boston, MA; Rikke Sarah Ogawa, AHIP, director, Louise M. Darling Biomedical Library and Science and Engineering Library, University of California\u2013Los Angeles; Shalu Gillum, AHIP, head, Public Services, Harriet F. Ginsburg Health Sciences Library, University of Central Florida College of Medicine\u2013Orlando; Shannon D. Jones, AHIP, director, Libraries, and associate professor, Medical University of South Carolina\u2013Charleston; Erinn Aspinall, AHIP, strategic initiatives librarian and communications coordinator, Health Sciences Library, University of Minnesota\u2013Minneapolis; and Christine Willis, AHIP, director, Knowledge Management & Learning Resources, Noble Learning Resource Center, Shepherd Center, Atlanta, GAThe online itinerary planner, sponsored by Wolters Kluwer, allowed attendees to peruse programs and events online. Complimentary WiFi was available throughout the Hyatt Regency Chicago, excluding the exhibit hall, courtesy of the JAMA Network. Live streaming was available on Twitter using the hashtag #MLANET19, and volunteer bloggers, the Local Assistance Committee, and the 2019 National Program Committee contributed to the official meeting blog with meeting tips, announcements, and more. For those seeking new jobs and prospective employers, the Job Placement Center was open from Saturday through Tuesday, and the MLA Resume Clinic was available Saturday through Monday. The Hall of Exhibits was open Saturday through Monday.AppendixClick here for additional data file.AppendixClick here for additional data file.JJ Pionke, MA, MSI,pionke@illinois.edu, Proceedings Coeditor and Applied Health Sciences Librarian, University Library, University of Illinois at Urbana-Champaign, 1408 West Gregory, Urbana IL 61801Ellen Aaronson, MLS, AHIP,aaronson.ellen@mayo.edu, Proceedings Coeditor and Librarian, Libraries, Mayo Clinic, 200 First Street SW, Rochester, MN 55905"} +{"text": "In their Target Article \u201cThe Prostitution Problem\u201d: Claims, Evidence, and Policy Outcomes, Benoit, Smith, Jansson, Healey, and Magnuson give an After thorough review of the available evidence, Benoit et al. concludeBenoit et al. go on toAlthough Benoit et al. do attenWhereas Benoit et al. appear tMany changes can be observed in the business of commercial sex of late. Due to economic, ideological, and technological developments, a diversification and professionalization of the sex industry has been noted Christians, fundamentalist Islamists, abolitionist feminists, social activists of diverse stripes, a cadre of Hollywood celebrities and corporate officials of T-visas granted (p. 71).However, the production of these high numbers has been critiqued for a lack of methodological transparency and source documentation, for incorrect extrapolations, and for unacceptable broadening of the definition of what constitutes a victim exploitation in their many forms. Maybe Benoit et al. started"} +{"text": "Journal of Educational Evaluation for Health Professions (JEEHP) was included in Embase, the invaluable biomedical literature database maintained by Elsevier, which provides over 32 million records published in over 8,300 indexed peer-reviewed journals. This represents another opportunity for the journal to be disseminated and searched by biomedical researchers from all over the world. Although JEEHP has been indexed in MEDLINE since March 2016, it was included in Embase in May 2018. The rigorous review process for being indexed in Embase provides further evidence of the journal\u2019s high quality and brand.We are proud to announce that in May 2018, Fundaci\u00f3n Educacion M\u00e9dica, Medical Education, Medical Teacher, and South-East Asian Journal of Medical Education. The World Federation for Medical Education Conference 2019 will be held at the Grand Walkerhill Seoul in Seoul, Korea from April 7 to 10, 2019 (http://www.wfme2019.org/). I hope to invite the authors who present at this conference to publish their results in JEEHP.Although JEEHP has been an affiliated journal of the World Federation for Medical Education since September 2016 [In April 2016, we adopted an open data policy ; howeverIn January 2018, the third version of the \u2018Principles of transparency and best practice in scholarly publishing\u2019 was announced by the Committee on Publication Ethics, the Directory of Open Access Journals, the Open Access Scholarly Publishers Association, and the World Association of Medical Editors. It consists of 16 items that should be announced and adhered to by scholarly journal editors and publishers . A complThis year, I invited a number of reviewers to review submissions to JEEHP. Some of them accepted the review request and provided invaluable comments that contributed to the better presentation of study results. Without their help, it would not be possible to publish this small, but unique, journal. I understand very well that they were all very busy, but they nonetheless shared their time to contribute to advances in educational evaluation for health professions. I appreciate them from the bottom of my heart. The reviewers for the 2018 issue are listed below:Abdolghani Abdollahimohammad, Katharina Brandl, Su-Jin Chae, Lap Ki Chan, Cheol-Woon Chung, Derek Clewley, Fabrizi Consorti, Lionel Di Marco, Kyung (Chris) T. Han, Geum-Hee Jeong, Karen Huhn, Yera Hur, Oscar Jerez, Sun Hee Kang, Nayoung Kim, Yong Sung Kim, Na Jin Kim, Young-Min Kim, Sue Kim, A Ra Cho, Seock-Ho Kim, Kwang Hwan Kim, Sun Kim, Oh Young Kwon, Young Hwan Lee, Eun Young Lim, Nesreen El Mekawy, Younjae Oh, Cesar A. Orsini, Robin Parish, Janghee Park, Mee Young Park, Quan Pham, Amelia Richardson, Dong Gi Seo, Ji-Hyun Seo, Ravi Shankar, Luiz Troncon, Julie Youm, Hon Yuen, Pete Yunyongying, Gagani Athauda, Fabrizio Consorti, and Gregory RoseWe published 3 articles on computerized adaptive testing in this year\u2019s issue introduction piece of SimulCAT, a software program developed for conducting CAT simulation studies ; post-hoIn the New Year, I hope to receive and publish more manuscripts with complete adherence to the journal\u2019s style and format with interesting topics for instructors in the medical and health fields."} +{"text": "Abstracthttps://doi.org/10.15468/fdzzal).This paper describes the herbarium (COFC) dataset of vascular plants of the University of Cordoba (SW Spain). This dataset is made up of two collections, the General collection and the Historical collection . This study has focused mainly on the General collection, which contains the largest number of vascular plant specimens, predominantly angiosperms, mainly provincial and regional , but also with a good representation of other areas of the Iberian Peninsula and neighboring countries. The place of collection is specified in 99.7% of the labels, about 35% being georeferenced, and it is estimated that, currently, about 86% of the material housed in the herbarium has been databased using Elysia v1.0. software. With more than 178 families, 1,178 genera, and 3,750 species, this collection not only has educational importance, but is a valuable research tool that has been useful for the development of important works such as \"Flora Vascular de Andaluc\u00eda Occidental\" and the \"Flora iberica\". The dataset described in this paper is registered with GBIF (accessible at It includes three botanical collections: one of fungi and two of vascular plants, the Historical collection and the General collection , the latter being the most significant. To these will be added in the future the recently created collections of bryophytes and algae, in the initial phase and barely significant. So far, 98.7% of the specimens have been databased and they can be accessed through the GBIF network (http://data.gbif.org). Some interesting data from the Historical collection are provided, but the dataset described in this paper covers exclusively the General collection.The herbarium (COFC) of the University of Cordoba (Spain) is located in the Rabanales Campus, on the outskirts of the city of Cordoba. It was created in 1977 and is associated with the Department of Botany, Ecology and Plant Physiology . The herbarium, of which Prof. J.A. Devesa is currently the curator, is registered in the Index Herbariorum with the acronym COFC , contains a total of 1,614 specimens of vascular plants arranged in 22 classes according to the Linnaean system . Most ofCentaurea L. (Asteraceae) and Festuca L. (Poaceae), within the \"Flora iberica\" project. This is one of the Spanish herbaria with greater representation of these genera. The herbarium, therefore, includes an important sample of the vascular plant biodiversity of the Iberian Peninsula, especially that of Western Andalusia (SW Spain), so it is not only essential for the knowledge and study of local flora, but also has been very useful for \"Flora de Andaluc\u00eda Occidental\" (http://www.floraiberica.org/).The General collection has a total of 61,377 specimens that have been recorded with different herbarium number, and there are more than 12,000 duplicate specimens of the gatherings. This collection is the fourth largest among the Andalusian collections in terms of the number of specimens , except for the data related to the genus Festuca, which have not been uploaded yet since they are still under study.This collection regularly increases, by about 1,250 specimens per year, and the dataset is periodically uploaded to the GBIF portals. The data referring to this collection can be found at The collection of vascular plants has 61,377 specimens belonging to 178 families, 1,178 genera, and 3,750 species. Of the specimens in the collection, 97.8% are identified at the species level and the remaining 2.2% only at the level of the genus, awaiting their review by a specialist.Angiospermae) belonging to the classes Magnoliopsida and Liliopsida . These are followed, in terms of representation, by ferns and related groups, with 991 specimens (1.61%) and the following distribution: class Polypodiopsida (740 specimens), Equisetopsida (139 specimens), Lycopodiopsida (107 specimens), and Psilotopsida (5 specimens). Finally, for gymnosperms (Gymnospermae) there are 353 specimens (0.58%), with the following distribution: Cycadopsida (2 specimens), Ginkgoopsida (1 specimen), Gnetopsida (51 specimens), and Pinopsida (299 specimens). In terms of diversity, Magnoliopsida , Pinopsida , and Polypodiopsida are the most diverse classes within each large group of vascular plants , Fabaceae , Poaceae , Lamiaceae , Caryophyllaceae , Plantaginaceae , Brassicaceae , Apiaceae , Ranunculaceae , and Boraginaceae , Trifolium , Festuca (811 specimens), Euphorbia (768 specimens), Plantago (750 specimens), Ranunculus (739 specimens), Medicago (724 specimens), Silene (722 specimens), Quercus (675 specimens), and Bromus (610 specimens) and Festuca (59 spp.), followed by Trifolium (41 spp.), Silene (40 spp.), Euphorbia (37 spp.), Ononis (37 spp.), Genista (35 spp.), Ranunculus (34 spp.), Astragalus (28 spp.), and Teucrium (27 spp.).The ten families that contribute most, in percentage terms, to the plant specimens conserved in the herbarium are: Kingdom: PlantaePhylum: TracheophytaClass: Cycadopsida, Equisetopsida, Ginkgoopsida, Gnetopsida, Liliopsida, Lycopodiopsida, Magnoliopsida, Pinopsida, Polypodiopsida, Psilotopsida.Family: Acanthaceae, Adoxaceae, Aizoaceae, Alismataceae, Amaranthaceae, Amaryllidaceae, Anacardiaceae, Annonaceae, Apiaceae, Apocynaceae, Aquifoliaceae, Araceae, Araliaceae, Araucariaceae, Arecaceae, Aristolochiaceae, Asparagaceae, Asphodelaceae, Aspleniaceae, Asteraceae, Athyriaceae, Balsaminaceae, Begoniaceae, Berberidaceae, Betulaceae, Bignoniaceae, Blechnaceae, Boraginaceae, Brassicaceae, Bromeliaceae, Butomaceae, Buxaceae, Cactaceae, Campanulaceae, Cannabaceae, Capparaceae, Caprifoliaceae, Caryophyllaceae, Casuarinaceae, Celastraceae, Ceratophyllaceae, Cistaceae, Cleomaceae, Clusiaceae, Colchicaceae, Commelinaceae, Convolvulaceae, Coriariaceae, Cornaceae, Crassulaceae, Cucurbitaceae, Culcitaceae, Cupressaceae, Cycadaceae, Cymodoceaceae, Cynomoriaceae, Cyperaceae, Cystopteridaceae, Cytinaceae, Davalliaceae, Dennstaedtiaceae, Didiereaceae, Dioscoreaceae, Drosophyllaceae, Dryopteridaceae, Ebenaceae, Elaeagnaceae, Elatinaceae, Ephedraceae, Equisetaceae, Ericaceae, Escalloniaceae, Euphorbiaceae, Fabaceae, Fagaceae, Frankeniaceae, Garryaceae, Gentianaceae, Geraniaceae, Ginkgoaceae, Grossulariaceae, Haloragaceae, Heliotropiaceae, Hydrangeaceae, Hydrocharitaceae, Hypericaceae, Iridaceae, Isoetaceae, Juglandaceae, Juncaceae, Juncaginaceae, Lamiaceae, Lauraceae, Lentibulariaceae, Liliaceae, Linaceae, Linderniaceae, Lycopodiaceae, Lythraceae, Magnoliaceae, Malvaceae, Marantaceae, Marsileaceae, Martyniaceae, Melanthiaceae, Meliaceae, Menispermaceae, Menyanthaceae, Molluginaceae, Montiaceae, Moraceae, Musaceae, Myricaceae, Myrtaceae, Nephrolepidaceae, Nyctaginaceae, Nymphaeaceae, Oleaceae, Onagraceae, Ophioglossaceae, Orchidaceae, Orobanchaceae, Osmundaceae, Oxalidaceae, Paeoniaceae, Papaveraceae, Passifloraceae, Paulowniaceae, Phrymaceae, Phyllanthaceae, Phytolaccaceae, Pinaceae, Piperaceae, Pittosporaceae, Plantaginaceae, Platanaceae, Plumbaginaceae, Poaceae, Polemoniaceae, Polygalaceae, Polygonaceae, Polypodiaceae, Portulacaceae, Potamogetonaceae, Primulaceae, Proteaceae, Pteridaceae, Rafflesiaceae, Ranunculaceae, Resedaceae, Rhamnaceae, Rosaceae, Rubiaceae, Ruppiaceae, Rutaceae, Salicaceae, Salviniaceae, Santalaceae, Sapindaceae, Saxifragaceae, Scrophulariaceae, Selaginellaceae, Simaroubaceae, Smilacaceae, Solanaceae, Tamaricaceae, Taxaceae, Tetradiclidaceae, Thelypteridaceae, Thymelaeaceae, Tropaeolaceae, Typhaceae, Ulmaceae, Urticaceae, Verbenaceae, Violaceae, Vitaceae, Zygophyllaceae.Most of the specimens in the collection are from Spanish territory , with the peninsular area being the best represented is the region with the highest number of specimens; specifically, within Andalusia, the province of Cordoba has the greatest representation , followed by Seville , Jaen , Huelva , and Cadiz ; while the minor ones are December, January and November .The usual procedures for the processing and storage in the herbarium of the plant material have been employed. The fresh material is dried by pressing, sometimes with simultaneous drying using an oven or heater. When it is dry, and prior to storage, the rotary freezing technique (at -18 \u00b0C) is used for four days in order to conserve the material and prevent its destruction by fungi and insects, thus avoiding subsequent infestations. This procedure is repeated approximately every six months. The specimens are stored in boxes inside compactor cabinets located in an isolation unit with controlled temperature and humidity. The families are arranged alphabetically, as are the genera within each family and the species within each genus.Once processed, the specimens go along the assembly line, where they are assembled and labeled. Subsequently, they are assigned a COFC accession number and databased using Elysia v1.0. software . It is eThe care and control of the collection includes its monitoring through the management and registration of all incoming and outgoing botanical gatherings that are the responsibility of the Herbarium Service, with the curator\u2019s supervision. The process includes space planning, sample relocation, sample assembly and repair, freezing to minimize the potential for insect infestation, and general repairs. Periodic checks are made in the storage area of the collections to detect possible effects of insects and harmful fungi.The quality control is mainly performed at three levels:In the identification phase/taxonomic criteria: For their inclusion in the herbarium, the specimens must be identified at the level of the species and, if appropriate, the infraspecific category, although for many genera there is material without identification of the species that is waiting to be reviewed by specialists. The main works used to identify the material are: \"Flora Vascular de Andaluc\u00eda Occidental\" (http://www.theplantlist.org/), Tropicos (http://www.tropicos.org), IPNI , and Euro+Med PlantBase , as well as the valid name recognized in \"Flora iberica\" (http://www.floraiberica.es/).1. idental\" , \"Flora idental\" , \"Flora idental\" , and \"Flidental\" . In caseidental\" and IV of the place of origin, with greater or lesser precision. At present, the georeferencing of the collection is being done using MGRS coordinates (1 km2 of precision) based on the information contained in the original label, using the tools of Google Earth (http://www.google.com/earth/index.html) and Iberpix (http://www.ign.es/iberpix2/visor/). These coordinates are automatically transformed into geographic coordinates when the herbarium information is transferred to the GBIF portal.2. In the phase of databasing and data export to the GBIF/Data records network: The first stage of the databasing of the collection was carried out with Herbar v3.7.1 software (Festuca). The Darwin Core biodiversity standards were used , encoded in UTF-8, is generated regularly and is available for download on the GBIF data portal via the Integrated Publishing Toolkit (IPT) of the University of Cordoba , through the GBIF Spanish network. The list of elements in the Darwin Core standard published through the GBIF network as well as their definitions and other information of interest can be found at https://dwc.tdwg.org.3. software , but aftsoftware , which iCOFC herbarium does not yet have its own funding. Since its creation, it has been dependent on the personnel and resources of the Department of Botany, Ecology and Plant Physiology of the University of Cordoba. Only more recently has it received additional funding, fruit of the efforts made by the two Curators who have been in charge, Profs. E. Ruiz de Clavijo (1977\u22122010) and J. A. Devesa (2011\u2212present). It had two grants at the beginning of the databasing of the collection (Complementary Funding of the Ministry of Education and Science), and since 2011 it has benefitted from the work of technical personnel hired for the maintenance, databasing, and georeferencing of the collection, in some cases financed by the Government of Spain, and in others by the Junta de Andaluc\u00eda. These grants and contracts are summarized below.Funding body: Ministry of Education and ScienceReference: CGL2007-28813-ELead researcher: E. Ruiz de ClavijoDuration: January 2008 to December 2008Amount: 32,900 eurosFunding body: Ministry of Education and ScienceReference: CGL2008-02241-E/BOSLead researcher: E. Ruiz de ClavijoDuration: January 2009 to December 2009Amount: 23,000 eurosProgram: Adaptation of the Herbaria of the Faculty of Sciences of the University of Cordoba to the GBIF framework (Subprogram: Complementary Actions)Funding body: Ministry of Science, Innovation, and UniversitiesLead researcher: E. Ruiz de ClavijoDuration: July 2006 to April 2007Program: Adaptation of the Herbaria of the Faculty of Sciences of the University of Cordoba to the GBIF framework (Subprogram: Complementary Actions)Funding body: Ministry of Science, Innovation, and UniversitiesLead researcher: E. Ruiz de ClavijoDuration: January 2008 to December 2008Program: Adaptation of the Herbaria of the Faculty of Sciences of the University of Cordoba to the GBIF framework (Subprogram: Complementary Actions)Funding body: Ministry of Science, Innovation, and UniversitiesLead researcher: E. Ruiz de ClavijoDuration: March 2009 to December 2009 (extended until 30\u221210\u22122010)Contracts for technical staff member:Program: Technical Personnel to Assist ResearchFunding body: Ministry of Science and InnovationReference: PTA2010-3438-ILead researcher: J. A. DevesaDuration: February 2011 to January 2014Program: Technical Personnel to Assist ResearchFunding body: Ministry of Education and Vocational TrainingReference: PTA2017-13723-ILead researcher: J. A. DevesaDuration: 2019\u22122021Contracts from the Youth Employment Plan:Program: National Youth Guarantee SystemFunding body: Ministry of Employment and Social SecurityLead researcher: PEJ-2014-A-82677Researcher: J. A. DevesaDuration: 2016\u22122017Program: National youth guarantee system and the youth employment operational programFunding body: Junta de Andaluc\u00edaReference: EJ-17-HerbLead researcher: J. A. DevesaDuration: June 2017 to May 2018Program: National youth guarantee system and the youth employment operational programFunding body: Junta de Andaluc\u00edaReference: EJI-17-RNM-260Lead researcher: J. A. DevesaDuration: January 2018 to July 2019Program: National youth guarantee system and the youth employment operational programFunding body: Ministry of Economy, Industry, and Competitivity, and Junta de Andaluc\u00edaReference: EJI-17-RNM-260Lead researcher: J. A. DevesaDuration: March 2019 to February 2020The following activities are being prioritized by the technical staff.Mounting, databasing, and inclusion of specimens from old collections: About 10,000 sheets of unmounted and unfiled specimens that accumulated in the period 1977\u22121987 are pending allocation of a sheet number or accession number, as well as databasing and inclusion in the General collection. Also, some 4,000 sheets have been allocated an accession number, but their data have not been registered in the database, probably due to a lack of technical personnel during that period and/or the absence of standardized databases. All this material has been identified, and most of it has been mounted. It has been arranged by family in distinctive blue boxes; currently, it is being databased using Elysia v1.0.a) These data were not available and so these specimens were not included in the taxonomic analysis or geographical coverage of this paper.Update the software and publication of data in GBIF: First, the migration of the database to the new version 2.0 of the Elysia software (Festuca need to be uploaded. This will be done once the study of its taxonomy and nomenclature has been completed (estimated date: December 2019). However, this paper has taken into account these records (811 so far) for the description of the collection.b) software will be Centaurea (Festuca (taxonomic revision in progress), two of the most complex genera of the peninsular flora with an excellent representation in the collection. It is estimated that 16% of all the material preserved in the collection corresponds to duplicates, and these are especially common for the genera Centaurea of various described taxa of the Iberian Peninsula are preserved in COFC . Facultad de Ciencias. Universidad de C\u00f3rdobaCharacter encoding: UTF-8Format name: Darwin Core Archive formatFormat version: 1.0Distribution: https://doi.org/10.15468/fdzzalPublication date of data: 2019-07-19Language: SpanishLicences of use: Creative Commons Attribution Non Commercial (CC-BY-NC) 4.0 LicenseMetadata language: SpanishDate of metadata creation: 2019-06-18Hierarchy level: Dataset"} +{"text": "Graduate of the Institute of Medicine and Pharmacy in Bucharest in 1964, medical doctor, title obtained in 1974 with the doctoral thesis \u201cCurrent therapeutic aspects in pituitary adenomas\u201d, neurosurgeon since 1979, he was the Head of Neurosurgery I Department, \u201cBagdasar-Arseni\u201d Clinical Emergency Hospital, coordinator of the Neuroscience Research Department of \u201cBagdasar-Arseni\u201d Clinical Emergency Hospital and has been professor of Neurosurgery since 1997. He has held prestigious positions such as vice-president of the World Federation of Neurosurgical Societies (WFNS), corresponding member of the Brazilian Academy of Neurosurgery, corresponding member of the Romanian Academy of Sciences, vice-president of Academia Multidisciplinaria Neurotraumatologica (AMN), and corresponding member of Romanian Academy of Medical Sciences.st Grade Researcher since May 2009.He has been 1Pediatric neurosurgery pathology, Academia Publishing House, for which he received \u201cGh. Marinescu\u201d prize of the Romanian Academy. He is co-author of 21 neurosurgical and neurological treaties and monographs. He is member of many editorial boards of international journals such as Child\u2019s Nervous System, Springer-Verlag, Germany; Surgical Neurology, USA; Acta Neurochirurgica, Springer-Verlag, Vienna; Asian Journal of Neurosurgery, Nagoya, Japan; Journal of Medicine and Life, Romania; etc.His scientific activity includes many articles published in ISI (Clarivate) indexed journals such as Neurosurgical Review, Surgical Neurology, Neurosurgery, Acta Neurochirurgia, etc., as well as articles published in journals indexed in international databases (PubMed): Neurology Psychiatry Neurosurgery; Pediatrics; Neurology studies and research; Journal of Pediatrics, obstetrics and gynecology; etc. Moreover, he has also published over 100 articles in Romanian journals and is the main author of 35 treaties and monographs published in Romania and abroad, such as He founded the neuroscience research department of \u201cBagdasar-Arseni\u201d Clinical Hospital in Bucharest and has led and been involved in many research projects.He has collaborated with prestigious universities abroad such as the University of Virginia, USA, Karolinska University, Sweden, Marburg University, Germany, Messina University, Italy.He holds a patent for \u201cUnitub Drainage\u201d, which he obtained in 2005. He applied the technique of ventriculo-peritoneal shunt-unitub drainage for the first time in Romania in 1985, currently being a procedure used as surgical treatment in children with primary and secondary hydrocephalus.For his activity and remarkable results, he has been awarded many prizes such as the National Order \u201cFaithful Service\u201d as Commander. He was also awarded the Doctor Honoris Causa title by universities in Gala\u0163i, Oradea, Chi\u015fin\u0103u, Ia\u015fi, Pite\u015fti, Constan\u0163a and was Visiting Professor at 11 universities, such as Harvard University in Boston, INI in Hannover, Mercer University in Atlanta, etc.In one of his latest articles, Prof. Alexandru Vlad Ciurea, MD, PhD, affirmed: \u201cEven for the most gifted neurosurgeons and despite modern medical devices, or for psychologists and famous neurologists, the brain remains a command center that has its enigmas\u201d. In an impressive ceremony that took place in Bucharest, on January 31, 2019, with a select audience, the Eminent Professor was awarded the honorable title \u201cCommander of Order of Romania\u201d. This order is rarely awarded only to prominent personalities with a major activity in promoting our country.\u201cAs graduate of \u201cAndrei \u015eaguna\u201d National College in Bra\u015fov, I had the privilege of studying by following \u201cthe footsteps\u201d of real patriots, people who participated in the great event of the Union! I was a student of the famous high school and I walked through the same corridors, passed through the same classrooms, through which many of the Union\u2019s personalities stepped in\u201d, justified the distinguished professor on March, 10 2019, at the entrance in \u201cAtelier\u201d Hall of the National Theatre in Bucharest, his wearing the high school uniform to what was going to be another new and fascinating lesson on health, titled \u201cAlzheimer understood by everyone\u201c.The famous neurosurgeon stated, \u201cAlzheimer is considered incurable, with a long pre-clinical period and a progressive course of the affection, from minor to severe forms of the disease. Many political, artistic and sports personalities have died from this disorder, and the main therapeutic method is prevention \u201d.Undoubtedly, the overwhelming personality, the extraordinary power of work and especially his tenacity and will, doubled by a permanent opening to novelty and a continuous availability, have made Prof. Alexandru Vlad Ciurea, MD, PhD, a complete neurosurgeon.Thank you for being, Prof. Alexandru Vlad Ciurea, MD,\u00a0PhD!"} +{"text": "Nature Communications; 10.1038/s41467-018-06375-y; published online 28 Sept 2018Correction to: In the original version of this Article, the affiliation of the first author, Maria F. Torres, \u2018Department of Biological Sciences, University of Cincinnati, Cincinnati, 45221, OH, USA\u2019 was incorrectly assigned as a present address and should have been listed as a full affiliation. This error has been corrected in both the PDF and HTML versions of the Article."} +{"text": "Oenanthe javanica, popularly known as water dropwort, has long been used in various ethnomedical systems in Asia, especially in China, Korean, and Japan, for treating various chronic and acute hepatitis, jaundice, alcohol hangovers, abdominal pain, and inflammatory conditions. The present review aims to provide a general report of the available literature on traditional uses, phytochemical, pharmacological, nutritional, and toxicological data related to the O. javanica as a potential source of new compounds with biological activities. Considering phytochemical studies, coumarins, flavonoids and flavonoid glycosides, organic acids, and polyphenols were the main classes of compounds identified in the whole plant which were correlated with their biological activities such as hepatoprotective, anti-inflammatory, immune enhancement, ethanol elimination, antioxidant, antiviral, neuroprotective, anti-cancer, anticoagulant, anti-fatigue, hypoglycemic, cardiovascular protection, analgesic, and insecticidal activities. Before modern drugs began to take shape in the medical care industry, people were highly dependent on conventional or traditional medicine, which have been recognized by the World Health Organization as reliable medicinal sources for therapeutic activities , 2. MediOenanthe javanica (Blume) DC. (Apiaceae), which is a small perennial herb, has been cultivated in tropical and temperate regions of Asia for thousands of years and has long been used as a folk remedy for alleviating a wide spectrum of diseases. A variety of biological activities of O. javanica have been reported, including hepatoprotective . However, at the dose of 3000\u2009mg/kg, it showed a decreasing effect on weight gain and lymphocyte number, and an increasing effect on neutrophil, but no effect on other tested items. Furthermore, within a 4-week recovery period, the induced toxicity was basically recovered [for mice , 15, 83.ecovered . O. javanica was reported by Xia and Li [ O. javanica was applied. There was also burning-like epidermal exfoliation on the lesions. The patient felt strong burning pain but no itching and was cured by 7-day anti-inflammatory treatment.In addition, a rare case of irritant contact dermatitis owing toa and Li , in whic O. javanica and the available scientific reports on its phytochemistry, pharmacological activities, and toxicology. It is worth mentioning that although scientific studies of bioactivities of O. javanica might justify some of its ethnomedicinal claims, the data are insufficient and, to some extent, preliminary. In the future, further systemic studies in humans are necessary. Furthermore, a subchronic toxicology of O. javanica at high dose was observed in rats, but the potential toxic component and its possible mechanism have not been revealed. It would also be beneficial for in vivo and clinical studies to evaluate the toxicity effects on the target organ.The present review collectively discussed the ethnomedicinal uses of"} +{"text": "Constant efforts of elite professionals in this important field are more and more, more known and, of course, more beneficial.Integrative dimension of capitalizing the sanogenic resources from Techirghiol lake area\u201d National Conference with international participation, that took place at Techirghiol Balneary and Rehabilitation Sanatorium, at the beginning of this month, what should be mentioned is the marking of the 119 years of clinical research and maritime balneary management and especially the 45 years since the inauguration of Techirghiol Balneary and Rehabilitation Sanatorium.Thus, to highlight only two of the these remarkable actions, \u201cThe high scientific event, organized admirably and directed by the energetic and inspired \u201cwand\u201d of lawyer Elena Roxana Alm\u0103\u015fan, PhD student and manager of the Sanatorium, was held in collaboration with the local and county decision makers and, among others, with the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, \u201cGrigore Antipa\u201d National Institute for Marine Research and Development, Romanian Society of Physical Medicine, Rehabilitation and Balneoclimatology, Romanian Society for NeuroRehabilitation, under the aegis of Romanian Medical Association and under the auspices of Medical Sciences Academy, \u201cCarol Davila\u201d University of Medicine and Pharmacy in Bucharest, and \u201cOvidius\u201d University in Constanta.The rehabilitation function of the human brain\u201d.The inaugural conference was held by the famous neurologist and psychiatrist, Prof. Dumitru Constantin Dulcan, MD, PhD, with the theme \u201cA special moment of the Conference was the round table dedicated to the implementation of the main educational components belonging to the neurorehabilitation European curriculum in Romania, to which many important personalities in the field have participated: Prof. Dafin Mure\u015fanu, MD, PhD, Prof. Ovidiu B\u0103jenaru, MD, PhD, Prof. Bogdan Popescu, MD, PhD, Prof. Gelu Onose, MD, PhD, Prof. Cristina Daia, MD, PhD, Prof. Volker H\u00f6mberg, MD, PhD, Prof. Giorgio Sandrini, MD, PhD.Another moment, with a powerful emotional impact, was the one of offering diplomas and medals to the employees, still working or retired, who were hired at the foundation of the Sanatorium, on August 1, 1973, and the evoking and homage paid to Cornelia D\u0103r\u00e2ng\u0103, MD, the first director of the institution (1973-1986).Techirghiol magazine, Arc peste timp brochure and the anastatic edition of Biodinamica lacului Techirghiol by Ion \u021auculescu.Among the materials offered to the participants, the following should be mentioned: the Abstracts published in a Special Issue of the valuable magazine \u201cJournal of Medicine and Life\u201d, th National Conference of Balneology, and Medical Rehabilitation, organized by the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology.Another remarkable event in this field took place this year in Aula Magna, Romanian Patriarchal Palace, under the patronage of the Academy of Medical Sciences and \u201cCarol Davila\u201d University of Medicine and Pharmacy in Bucharest, this being the 15The dynamic and hearty manager of the Institute, Horia L\u0103z\u0103rescu, MD, PhD, managed to invite both the managers of the best spa resorts in Romania and the mayors of these resorts to this valuable scientific event.The Conference had 12 scientific sessions and round tables, in which 87 scientific communications were presented and elaborated by 115 specialists on the following themes: \u201cNovelties in balneology\u201d, \u201cMedical rehabilitation in neurological and cardiovascular diseases\u201c, \u201cMedical rehabilitation in rare diseases of children\u201d, \u201cMusculoskeletal ultrasound in monitoring the medical rehabilitation treatment\u201d.On this occasion, the National Institute of Rehabilitation, Physical Medicine, and Balneoclimatology organized a special festivity, during which 15 spa resorts were awarded prizes for the quality of natural therapeutic factors, treatment centers, and the involvement of local public administration, as well as the therapeutical mineral waters. The excellence diplomas and the medals of honor were offered to the mayors of the spa resorts and the managers of the sanatoriums or treatment centers.Recuperarea Medical\u0103 de faz\u0103 acut\u0103\u201d, edited by Prof. Adriana Sarah Nica, MD, PhD.\u201cCarol Davila\u201d University Press of \u201cCarol Davila\u201d University of Medicine and Pharmacy in Bucharest was very much appreciated at this remarkable event, being present with specialty bookstands, among which the Romanian version of \u201cExecutive Editor Professor Eng. Victor Lorin Purcarea, PhD"} +{"text": "Background: During the past few decades there has been a growing interest on the part of many governments in the creation of biobanks. Nevertheless, this would be impossible without participation of many donors who offer samples of their biological material for scientific research. Therefore, the aim of this paper is to provide an overview of the existing research on social attitudes towards biobanking. Material and Methods: A literature search was conducted in the database of MEDLINE (PubMed). 61 papers were included in the analysis. The retrieved articles were assessed using a thematic analysis. Results: Eight main themes were identified: (1) public knowledge about biobanks, (2) public views on biobanking, (3) willingness to donate, (4) donors\u2019 motivations, (5) perceived benefits and risks of biobanking, (6) preferred type of consent, (7) trust toward biobanks, and (8) demographic characteristics of potential donors. Conclusions: Although the public lacks knowledge about biobanking, many individuals declare willingness to donate. Their will is influenced by: their knowledge about biobanking, the type of donated tissue, research purpose, concerns over the safety of the data, preferred type of consent, and trust towards biobanks. During the past few decades there has been a dynamic development of biobanks . It was As each biobank exists in a unique geographical, social, and historical context , donatioThus, the aim of this review is to identify, categorize, and analyse the main themes appearing in the existing research on social attitudes toward biobanking of human samples and data. It also discusses ways to improve social perception of and trust toward biobanks.A literature search was conducted in the database of MEDLINE (PubMed) using a combination of key words: \u2018biobank\u2019, \u2018biobanking\u2019, \u2018tissue bank\u2019, \u2018donors\u2019, \u2018public opinion\u2019, \u2018social attitudes\u2019, and \u2018participation in the research\u2019. To ensure the systematic aspect of the search, it was carried out twice: in November 2018 by J.D. and in January 2019 by J.P., and was limited to the material published after the year 2000.The initial search identified 1161 publications, which were then selected on the basis of their titles and abstracts. Articles were included if they reported empirical studies on social attitudes toward biobanking, were written in English, and published in peer-reviewed journals. Papers were excluded if they focused on the theoretical aspects of biobanking or did not report on social attitudes toward biobanking. Comments, experts\u2019 opinions, and letters to the editors were also excluded. These inclusion/exclusion criteria and additional reviews of the references of the selected articles yielded 61 articles which were read and analysed.n = 37) [Most research involved quantitative studies n = 3 [7,9,10,n = 37) ,47,48,49n = 37) ,52,53,54n = 37) ,57,58,59n = 37) ,60,61,62n = 37) ,64,65,66Twenty-four studies were conducted in North America: 22 in the U.S. ,54,57,62The retrieved articles were analysed using a thematic analysis . The stuAlthough biobanks exist in many countries, a 2010 Eurobarometer study on biotechnology has demonstrated that two-thirds of Europeans have never heard about biobanks and less than 2% search for information about biobanking. A higher awareness was observed in Scandinavian countries, including Iceland 80%), Sweden (75%), and Norway (65%) 0%, Swede. InfinitSimilarly, up to 67% of Americans have not heard about biobanks and manyDespite the deficits in knowledge, most research showed that public opinion on biobanking is generally positive and supports the idea of creating local biobanks. In Finland, 77% of respondents felt positive about such a project, while only 11% were against it . In a ScBetter knowledge and positive opinions on biobanks correlate positively with respondents\u2019 willingness to donate. In a Pan-European study, only 10% of respondents who had never heard about biobanks would not donate . For insRespondents\u2019 willingness to donate was determined by the type of donated tissues, as the public were especially likely to donate blood, cancer, skin, and kidney tissues , but werRespondents\u2019 willingness to donate also depended on access to the information about the research, as many donors wanted to know who was conducting the research and where the research was being conducted, what was its purpose, who would have access to research results, and where and how the samples would be stored ,12,51. DIn contrast, the donors may be discouraged by inadequate knowledge on biobanking ,40,60, dMost donors are driven by altruistic motives ,45,58,59Although respondents propounded for the social benefits of biobanking over personal ones, they also believed that donation should benefit both parties . NeverthThe most expected benefit resulting from biobanking was an increase in knowledge about many diseases and the development of novel therapies ,58,59,62Nevertheless, for the majority of respondents, participation in a biobank was a risky enterprise as they were afraid of the possibility of linking biological samples with donors\u2019 personal data ,30,34,52Informed consent in the context of biobanking is a hotly discussed ethical and societal issue. Classic consent is not possible due to objective reasons\u2014biospecimens are used in much research, by many scientists, working at different places. Therefore, new models of consent are proposed, such as blanket consent , broad consent , dynamic consent , or tiered consent (research can be subdivided into tiers or categories and participants can specify the types of research for which their specimens will be used). Although, from a biobank\u2019s perspective, broad consent is preferable , it is nTrust toward biobanks correlates positively with the willingness to donate, preference for broad consent, and decreases perception of the risks related to the privacy and confidentiality of samples ,48,58,61Interestingly, lack of trust was significantly high among ethnic minorities: African-Americans, Mexican-Americans, Native Americans, Hawaii and Alaskan Natives, which resulted from their negative experiences with colonization, eugenics, and medical experiments ,25,54,57Some studies suggest that middle-aged persons and older are more favorable toward donation, trust biobanks, and accept broad consent more often ,29,30,43Positive attitudes toward donation were more common among respondents with higher economic status ,40, who Ethnic minorities were generally less eager to share their samples than people of European ancestry. They also expect re-consent more often ,23,48.While religious beliefs did not seem to influence donors\u2019 decisions ,28, in tThis review of the research confirms that, although a large part of respondents do not possess knowledge about biobanking ,61, manyIt should also be emphasized that different attitudes toward biobanking result from social, cultural, and religious variances, which determine what types of tissue people are ready to donate, the type of research they are eager to participate in, and the consent model they prefer. Thus, while planning a biobank, it is crucial to address these socio-cultural circumstances, as it warrants respect for the donors and ensures the success of the recruitment process .Thus, active engagement of the donors in a biobank\u2019s activity should not be viewed as an obstacle, but as a factor that enables their recruitment. Consequently, many authors argue that the organization of any biobank requires building a unique culture of trust, which should include: transparency of the biobank\u2019s activity, appreciation of the donors, active involvement of local communities in planning and control of biobank activity, strengthening of bioethical committees in the organization and supervision of biobanks, and mutual communication with individual donors. Thus, recommendations include that donors have to have a chance to express their expectations and fears, receive clear and communicable leaflets, and feel in control . Further strategies include using the media of mass communication, including the Internet and social media; communication with representatives of patients\u2019 organizations, local community and other stakeholders; promotion of active participation and engagement of the donors in promoting the idea of biobanking; access to up-to-date information on a biobank\u2019s research and its results; contact with researchers; access to research results; and references to common good and altruism, taking care of the cultural and religious diversity of the donors ,27,56. TAlthough this study brings new insight into the public attitudes toward biobanking of human biological material for research purposes, it also has some limitations. Searching was limited to one database and some studies could not be identified, but this limitation should not change the general view and conclusions. Moreover, as analysed studies were conducted with different populations, it is hard to make quantitative comparisons. However, qualitative analysis is still possible and justified. In the future one should strive for strict quantitative analysis of public attitudes towards biobanking.While some limitations may exist in this paper, some advantages should also be acknowledged. Our review indicates that, although the majority of respondents lack basic knowledge about biobanking, many are open to donation and support the idea of establishing biobanks. Willingness for donation is influenced by multiple socio-cultural factors, including: the knowledge about biobanking, the type of donated tissue, research purpose and ethical standards, concerns over the safety of the data, positive recommendation by the bioethical committee, and commercial or non-scientific use of their samples. What is equally important is that most of the donors are driven by altruistic motives. Another notable finding is that respondents fear linking biological samples with their personal data, and access to their sensitive data by the government, insurance companies, and employers, and, consequently, discrimination or stigmatization. In particular, they are afraid of using their samples in research contrary to their values. Thus, although many donors accept broad consent, if available, other options are preferable, i.e., dynamic consent. This review also shows that the public trust public and national biobanking institutions rather than commercial and foreign institutions; trust toward biobanks links positively with willingness to donate, preference for broad consent, and links negatively with concerns about privacy protection and being a member of ethnic minorities. Biobankers who establish and manage their biobanks should take into account socio-cultural circumstances and care about a culture of trust towards biobanks, research, and scientists."} +{"text": "Global 0.5- by 0.5-degree resolution estimates are presented on the fate of nitrogen (N) stemming from point and nonpoint sources, including plant uptake, denitrification, leaching from the rooting zone, rapid flow through shallow groundwater, and slow flow through deep groundwater to riverine systems. Historical N inputs are used to describe the N flows in groundwater. For nonpoint N sources , calculations are based on local hydrology, climate, geology, soils, climate and land use combined with data for 1995 on crop production, N inputs from N fertilizers and animal manure, and estimates for ammonia emissions, biological N fixation, and N deposition. For point sources, our estimates are based on population densities and human N emissions, sanitation, and treatment. The results provide a first insight into the magnitude of the N losses from soil-plant systems and point sources in various parts of the world, and the fate of N during transport in atmosphere, groundwater, and surface water. The contribution to the river N load by anthropogenic N pollution is dominant in many river basins in Europe, Asia, and North Africa. Our model results explain much of the variation in measured N export from different world river basins."} +{"text": "Norman JE, Marlow N, Messow C-M, et al, for the OPPTIMUM study group. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet 387: 2106\u2013162016; \u2014In this Article, ten neonatal deaths (eight in the progesterone and two in the control group) were incorrectly categorised as postneonatal deaths, with no effect on the primary outcome and study conclusions. These corrections have been made online as of Jan 17, 2019, and the supplementary appendix of this Article has also been corrected as of Jan 17, 2019."} +{"text": "We read with great interest the article in the JFirst, a significant alarming issue is the reference to \u201cchili peppers\u201d. The authors defined them as \u201cfresh and dried chili peppers, but not including sweet capsicum or black pepper\u201d. However, the authors failed to notice the difference in dried and processed chilis versus the fresh chili. Fresh chili is more nutrient-rich due to bioactive ingredients, including capsaicin, vitamin C, and other nutrients such as vitamins A, K, and B6, and potassium . SecondlAdditionally, there have been a lot of other confounding variables which would lead to the variation in cognitive decline, despite the adjustment in this research for intake of fat, smoking, alcohol drinking, income, urbanicity, education, physical activity, dietary patterns, BMI and hypertension. For example, the uptake of some medications , some cIn summary, the self-reported nature of the data and the missing confounding variables can hardly make this analysis comprehensive and reliable to underline an association between chili consumption and cognitive decline."} +{"text": "Low-histamine diets are currently used to reduce symptoms of histamine intolerance, a disorder in histamine homeostasis that increases plasma levels, mainly due to reduced diamine-oxidase (DAO) activity. These diets exclude foods, many of them of plant origin, which patients associate with the onset of the symptomatology. This study aimed to review the existing data on histamine and other biogenic amine contents in nonfermented plant-origin foods, as well as on their origin and evolution during the storage or culinary process. The only plant-origin products with significant levels of histamine were eggplant, spinach, tomato, and avocado, each showing a great variability in content. Putrescine has been found in practically all plant-origin foods, probably due to its physiological origin. The high contents of putrescine in certain products could also be related to the triggering of the symptomatology by enzymatic competition with histamine. Additionally, high spermidine contents found in some foods should also be taken into account in these diets, because it can also be metabolized by DAO, albeit with a lower affinity. It is recommended to consume plant-origin foods that are boiled or are of maximum freshness to reduce biogenic amine intake. In recent years, various diets have been proposed for the treatment of histamine intolerance ,5,6,7,8.As described in the literature and scientific reports issued by the European Food Safety Authority (EFSA) and a joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) committee, histamine intolerance is a disorder associated with increased plasma histamine levels and is recognized as clinically different from the more established histamine intoxication ,10. AlthAOC1 on chromosome 7) have been associated with lower DAO activity [Diamine oxidase (DAO) is the main enzyme responsible for the metabolism of histamine and other amines at the intestinal level, and impaired DAO activity is one of the main causes of histamine intolerance ,12,13. Tactivity ,15,16. Tactivity . Anotheractivity .The symptoms of histamine intolerance are numerous and highly variable, due to the effects and functions of histamine in multiple organs and systems of the body. They include gastrointestinal , dermatological , respiratory , cardiovascular (hypotonia and arrhythmias), and neurological (headaches) symptoms, and it is common for more than one disorder to occur simultaneously ,11,12. SIn order to carry out a correct dietary treatment of histamine intolerance, it is necessary to know what foods may contain this amine and what factors influence its accumulation. Likewise, it is also important to consider the occurrence of other amines that are also metabolized by the DAO enzyme. In contrast to plant-origin foods, there is more available information on the contents of histamine and other amines in fish and fish derivatives and all types of fermented products , in which their presence is attributed to the aminogenic activity of spoilage microorganisms and also to fermentative microorganisms ,10,29. TDue to the information available on the contents of biogenic amines in nonfermented plant-origin foods being scarce, the aim of this study was to review the existing data on the contents of histamine and other biogenic amines in these types of products, as well as their origin and evolution during storage or cooking.A selective search of scientific literature dealing with biogenic amine contents in nonfermented plant-origin foods, including vegetables, fruits, and cereals, was performed. The bibliographic search was carried out in the PubMed and Web of Science databases using the following keywords: \u201chistamine\u201d, \u201cbiogenic amines\u201d, \u201ctyramine\u201d, \u201cputrescine\u201d, \u201ccadaverine\u201d, \u201cplant-origin food\u201d, \u201cfood samples\u201d, \u201cstorage\u201d, \u201ccooking\u201d, \u201cfruit\u201d, \u201cvegetable\u201d, \u201clegume\u201d, \u201ccereal\u201d, \u201cspinach\u201d, \u201ceggplant\u201d, \u201ctomato\u201d, \u201ccitrus\u201d, \u201cmodified atmosphere packaging\u201d, and \u201cmicrobial decarboxylase activity\u201d. Original analytical studies, reviews, and table compilations of content in food were included. Articles published before 1990 were excluded from this review. Apart from data obtained from the literature, data on the biogenic amine content of plant-origin foods from our own database of Spanish market products were also used. Specifically, histamine, tyramine, putrescine, and cadaverine contents of 25 types of vegetables, 19 fruits, and 8 cereals were included.In this section, the contents of biogenic amines in different plant-origin foods are reviewed, using our own database and data from studies published by other authors. A total of 20 studies reporting data on biogenic amine contents in such foods were found. Most provided data on putrescine contents , and only a few included other amines, such as histamine, tyramine, and cadaverine.The only products found to contain significant levels of histamine were eggplant, spinach, and tomato, each showing a great variability in content, both in samples from the same study and among different studies. Histamine values ranged from 4.2 to 100.6 mg/kg in eggplant, from 9.5 to 69.7 mg/kg in spinach, and from not detected to 17.1 mg/kg in tomato. In the case of asparagus, pumpkin, and chard, histamine was found in only a few samples and at very low levels (<2 mg/kg).Histamine occurs naturally in certain foods ,32, whicEnterococcus isolated from plants and fruits, mainly E. faecium, E. mundtii, and E. casseliflavus [Tyramine has been found in more foods than histamine, although in lower concentrations, in no case exceeding 10 mg/kg. It should be noted that histamine-containing foods also contained tyramine . Although there is very little information about the origin of tyramine in nonfermented vegetables, its presence seems to be associated with microbial aminogenic activity. The ability to form tyramine has been reported for bacteria of the genus liflavus .Clostridium spp. [Putrescine has been detected in all the studied vegetables and legumes, although its content varied greatly among foods and sometimes also within the same product. In most vegetables and legumes, the average values ranged from 1 to 25 mg/kg. However, some samples of green pepper, eggplant, sweet corn, green and purple beans, spinach, tomato ketchup, soybeans, and peas had strikingly high putrescine contents, in some cases exceeding 200 mg/kg . The putium spp. . Accordiium spp. , the higium spp. have sugCadaverine, like tyramine, has been described in few vegetables and legumes and in relatively low concentrations, with average values that in no case exceeded 8 mg/kg. The values reported by Nishimura et al. in onionAvocado and kiwi, and grapefruit, orange, and pineapple juices, are the only products in this category for which the presence of histamine has been reported, but not in all studies. The 23 mg/kg of histamine in avocado reported by Jarisch et al. stands oSimilarly, very few fruits contained tyramine, and levels have always been low . AvocadoPutrescine has been found in practically all the fruits and nuts, with the highest levels in orange, orange juice, mandarin, grapefruit, grapefruit juice, banana, passion fruit, and pistachio. The range of contents of this amine in citrus fruits and their juices has been very broad, varying from not detected to as high as 200 mg/kg. Suggested explanations for this variability have included different origins, cultivation, and transport and storage conditions ,42,43,44The only fruits with a notable content of cadaverine were bananas and sunflower seeds, for which Nishimura et al. reportedPutrescine contents in wholemeal bread were slightly higher than in bread made with refined flour. In white bread, low contents of cadaverine have also been reported, although only in one study, and from the analysis of two samples.The variability of amine contents observed among samples of the same product can be attributed mainly to conditions of production, transport, and storage .The storage temperature is one of the most important factors in the formation of biogenic amines ,29. RefrA study conducted by Simon-Sarkadi et al. showed aLavizzari et al. also repModified atmosphere packaging, together with low storage temperatures, is commonly used to extend the life of fresh vegetables and fruits. This type of packaging can influence the capacity of microorganisms to form amines ,58,60. EAnother factor that can affect the content of biogenic amines in foods of plant origin, especially vegetables, is the culinary process. Again, the results reported in the literature were variable, depending on the type of cooking and the amine in question. Latorre-Moratalla et al. evaluateConversely, three recent studies have shown an increase in amine levels after a cooking process. According to Lo Scalzo et al. , boilingAmines are thermostable compounds, so in principle changes in contents can only be due to their transfer to the cooking water or by dilution or concentration effects of the culinary process, in which the food gains or loses water.At present, the main strategy to prevent the onset of histamine intolerance symptoms is to follow a low-histamine diet. Its efficacy has been demonstrated in different clinical studies, which have always described an improvement or remission of gastrointestinal, dermatological, and neurological symptoms ,65,66,67Current low-histamine diets exclude foods that patients associate with the onset of symptoms ,5,6,7,8,Putrescine, cadaverine, and tyramine are all substrates of the DAO enzyme, so if present in high amounts they may increase the adverse effects of histamine by competing as rival substrates or for binding sites in the intestinal mucosa ,9,68,69.The polyamines spermidine and spermine can also be metabolized by DAO, albeit with a lower affinity ,69, and Finally, the levels of biogenic amines and polyamines found in kiwi, papaya, strawberry, pineapple, and plum are too low to justify their exclusion. Some authors consider these foods, along with others such as milk, shellfish, and eggs, as endogenous histamine releasers, although by mechanisms still not well understood ,11,70.Biogenic amine data in nonfermented plant-origin foods from the different reviewed studies showed a great variability both within the same food item and among them. Putrescine was the most frequent biogenic amine found in fresh vegetables, legumes, fruits, and cereals, and only a limited number of products contained relevant levels of histamine . Tyramine and cadaverine were usually more scarcely found in plant-origin foods. Generally, low levels of histamine and putrescine may have a physiological origin. However, undesirable microbial enzymatic activity during production or storage may lead to the accumulation of high levels of these amines.No single trend has emerged in the evolution of amine contents during refrigerated storage, which might be at least partly due to the different experimental designs of the studies. In some cases, refrigeration seems to have prevented the formation of certain amines, but this remains a hypothesis, as no study performed a comparative analysis of samples stored under refrigeration and at room temperature. The increase in the biogenic amine content during refrigerated storage reported by other authors may be attributed to bacterial activity. Additionally, some studies have observed an influence of culinary process on the biogenic amine content, mainly derived from the transfer of these compounds to the boiling water or by dilution or concentration effects of the applied treatment.The exclusion of a high number of plant-origin foods from low-histamine diets cannot be accounted for by their histamine contents, but is more likely due to high levels of putrescine or spermidine. The plant-origin foods consumed by people with histamine intolerance should be of maximum freshness, since histamine and other amines may continue to form during refrigerated storage. The cooking of vegetables in water (boiling) is another relevant strategy for this population, since it can reduce the contents of histamine and other amines in the food."} +{"text": "R2 values from random-forest analyses and interpreted these values as the proportion of BMI variation explained by the early-life gut microbiota, concluding that over 50% of variation in BMI at 12\u2009years was explained by gut microbiota at 2\u2009years cohort, we observed that only 10.3% of variation in BMI at 1\u2009year was collectively explained by maternal BMI, race, socioeconomic status, smoking, delivery mode, parity, breastfeeding, infant sex, birth weight, and gestational age . However, other key risk factors of childhood obesity, including maternal BMI, smoking, child diet, and physical activity, were not accounted for . AlthougFinally, we applaud the authors for defining conceptual frameworks and causal pathways, where they conceive breastfeeding, mode of delivery, antibiotics, and gestational age as confounders and/or mediators of the association between gut microbiota and BMI, in accordance with previous observations from the CHILD cohort . We also"} +{"text": "Scientific Reports 10.1038/s41598-018-33875-0, published online 22 October 2018Correction to: In the original HTML version of this Article, Yun-Fang Jia was incorrectly affiliated with \u2018Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA\u2019.This error has now been corrected in the HTML version of the Article, the PDF version was correct at the time of publication."} +{"text": "AbstractNitzschia with 40 taxa is far the most important genus followed by Navicula s.l. and Pinnularia and with 15 and 13 taxa respectively. Particular attention was paid to the local research of students found in unpublished theses at bachelor, licentiate, master and PhD level. Diatom records in these works are almost all restricted to genus level, although in the last decade an attempt to delimit species can be observed. This accompanies the renewed taxonomic interest in the Congo basin during the last decade. Renewed taxonomic interest can also be seen in the genera: the first period being situated during the lumping period, while more recent works follow the current taxonomic classification, for example Navicula s.l. versus Navicula, Cavinula, Craticula, Diadesmis, Geissleria, Humidophila, Luticola, etc.An overview of the diatom research in the DR Congo is given based on literature data starting in 1938 with the work of Zanon and excluding the East African Lakes as these were already discussed in previous papers. For each literature record the diatom genera mentioned are presented as well as all diatom taxa described from the Congo as new. In total, 106 new taxa were documented, of which In the Democratic Republic of the Congo (DR Congo), research in the field of plant biology mostly concerned the study of terrestrial forest ecosystems , while tEarly publications on freshwater algae in tropical Africa focused on the great lakes of the Albertine rift: Malawi (Nyassa/Nyasa), Tanganyika (Tanganika) and Victoria (Victoria Nyanzae) e.g. . A revieThe present paper aims to give an overview of the research that has been conducted in the DR Congo or that has investigated Congolese material, not only found in international publications, but also by means of local publications as well as unpublished theses at different levels .Initially international publications on algae, and more specifically on the diatoms, of DR Congo were searched for on the Web of Science and in the available international literature. Subsequently, inquiries were made regarding papers that were published locally in journals of the different universities in DR Congo and in final reports of national and international projects. The last step was to retrieve all theses, PhD level and other dissertations from universities and scientific institutions in DR Congo. Licentiate is an academic degree below that of a PhD, used in Belgium (and the DR Congo), and obtained after a university study of 4 to 5 years. In the Bachelor-Master structure, it is the degree that corresponds to a Master.A brief overview follows on the diatom research conducted on materials collected in DR Congo, including the former Congo and the Republic of Zaire, as found in mainstream literature, thus taking into consideration only published work accessible to the international scientific community.Pinnularia Ehrenberg, the others belonging to the genera Cocconeis Ehrenberg, Cymbella C. Agardh, Eunotia Ehrenberg, Neidium Pfitzer and Synedra Ehrenberg with a drawing (fig. 27) from a puddle on the Karisimbi volcano in the region Lake Kivu and mentioned this taxon name also (on page 545) in his species list of the diatoms from the region of Lake Kivu. However, in the same publication Pinnulariaborealisvar.africana v. n. (on page 556) and Pinnulariacongolensis n. sp. (on page 571) and in the species list he mentioned sample nr 5 from a puddle on the Karisimbi volcano and sample nr 21 from a puddle from Nanindhja respectively. However, no description is given for these two taxa, consequently both names have to be considered nomina nuda and therefore invalidly published. Two decades later Pinnulariaborealisvar.congolensis to species level: Pinnulariacongolensis (Zanon) Cholnoky.th century by that of Nitzschia Hassall, 11 to Navicula Bory and 6 to Eunotia. The other taxa are from more than 10 other genera including Achnanthes Bory, Amphora Ehrenberg, Caloneis Cleve, Cymbella, Fragilaria Lyngbye, Gomphonema Ehrenberg, Pinnularia, Stauroneis Ehrenberg, Stephanodiscus Ehrenberg and Surirella Turpin W. Smith, Rhopalodia O. M\u00fcller, Rhoicosphenia Grunow and Synedra.Further studies which included diatoms, were carried out in the Kivu region in the 1950\u2019s by st century research on algae of Lake Kivu continued with the work of At the beginning of the 21We have not included the research conducted on diatoms of Lake Tanganyika because this ancient lake, located on the territory of four African countries , does not fall within the scope of this paper. Moreover, there are a number of reports regarding this lake which have been produced in the last decades e.g. , 2006.Coscinodiscus Ehrenberg, one Craspedodiscus Ehrenberg, one Melosira C. Agardh, nine Nitzschia and one Synedra. It should be noted that some marine species are included in the results of these surveys, which is not surprising as the two localities are close to the mouth of the Congo River into the Atlantic Ocean. In 1948, Kufferath reported on the plankton of the Congo River near Makanza, formerly called New Antwerp, halfway between Kisangani and Kinshasa in the Equateur province. Among the 25 taxa Nitzschia species in the vicinity of Yangambi. The dominant genera were Eunotia, Cocconeis and Achnanthes; the other genera mentioned are: Bacillaria Ehrenberg, Caloneis, Coscinodiscus Ehrenberg, Cyclotella K\u00fctzing ex Br\u00e9bisson, Diatoma Bory, Diploneis (Ehrenberg) Cleve, Epithemia K\u00fctzing, Frustulia Rabenhorst, Gomphonema, Gyrosigma Hassall, Cymbella, Navicula, Nitzschia, Pleurostaurum (Rabenhorst) C. Janisch, Pinnularia, Stauroneis, Surirella, Synedra and some other centric diatoms. Diatom research in the Tshopo province was started again at the end of the 20th century, as is shown in the publication record. The Congo River as well as localities downstream the Lindi River, a major tributary of the Congo river, the Tshopo River and several small rivers and ponds in Kisangani were studied by Gomphonema species, G.zairense Comp\u00e8re, was described from the Tshopo River (Comp\u00e8re 1995) J.C. Taylor and Cocquyt, E.leonardii J.C. Taylor & Cocquyt, E.rudis Cocquyt & M. de Haan and Geisslerialubiluensis Cocquyt & Lokele , Cylindrotheca Rabenhorst, Cymbella, Diatoma, Epithemia, Eunotia, Fragilaria, Frustulia, Gomphonema, Gyrosigma, Navicula, Nitzschia, Pinnularia, Rhopalodia, Surirella, Synedra, Tabellaria Ehrenberg ex K\u00fctzing , was also investigated. It is located 4.5 km from the old road to Buta in the north of the city. Mbuyu and only four were found in the benthos .A pond (\u00e9tang du Grand-s\u00e9minaire) in Kisangani, dominated by yu Table reportedka Table studied re Table reportedya Table studied Melosira was found to be dominant in the stomach contents of Citharinus sp., a tropical African lutefish, and Labeo sp., a genus of carp, while Cymbella and Navicula were found in Distichodus sp., an African ray-finned fish. In addition to diatoms belonging to these three genera, 15 other genera were reported: Amphora, Amphipleura, Arcella Ehrenberg, Cocconeis, Caloneis, Cymatopleura, Cylindrotheca, Diatoma, Fragilaria, Gomphonema, Gyrosigma, Nitzschia, Pinnularia, Surirella and Synedra.Asterionella, Aulacoseira Thwaites, Cyclotella, Cymbella, Encyonema K\u00fctzing, Eunotia, Fragilariforma D.M. Williams & Round, Frustulia, Gomphonema, Navicula, Nitzschia, Pinnularia, Sellaphora Mereschkowsky, Stenopterobia (Br\u00e9bisson) Van Heurck and Surirella. For the benthos and epiphyton a total of 13 taxa were reported . Most were the same genera as reported in the plankton, however Asterionella and Cymbella were not present in the periphytic samples while Cymatopleura was present but not in the plankton.The Boyekoli Ebale Congo 2010 expedition, together with initiatives taken by the VLIR\u2013UOS at the University of Kisangani and the FORETS project at Yangambi, encouraged a number of students to choose diatom related subjects for their theses. In 2013, two students investigated the diatoms of some fish ponds at NgeneNgene, about 20 km from the city center of Kisangani. One thesis concentrated on the diatoms in the phytoplankton (Mosunga), the other on the benthos and the epiphyton (Mukinzi) according to the classification of Robyns Krammer, Diploneis, Encyonema, Encyonopsis Krammer, Fragilaria, Fragilariforma, Frustulia, Gomphonema, Luticola D.G. Mann, Neidium, Nitzschia, Orthoseira Thwaites, Placoneis Mereschkowsky, Planothidium Round & Bukhtiyarova, Pinnularia, Sellaphora, Stauroneis, Stenopterobia, Surirella and Ulnaria (K\u00fctzing) Comp\u00e8re. A professional bachelor thesis at the Thomas More University of Applied Sciences, Geel, Belgium, was written by Madden on epiphytic diatoms growing on a restricted number of Nymphaealotus herbarium specimens from the same phytogeographic region (VI) Levkov, Humidophila Lowe, Kociolek, Johansen, Van de Vijver, Lange-Bertalot & Kopalov\u00e1, Iconella, Mayamaea Lange-Bertalot, Navicula, Nupela Vyverman & Comp\u00e8re, Staurosira Ehrenberg, Staurosirella D.M. Williams & Round.Okito studied diatoms present on herbarium material of aquatic plants collected during the 20f Robyns and keptDuring the academic year 2017\u20132018 several other students started studying diatoms in rivers in the Tshopo province. Although most are not finished at the time of publication of the present paper, the preliminary titles of these theses are included in Table Achnanthes, Actinella, Aulacoseira, Bacillaria, Cocconeis, Cyclotella, Diadesmis, Diatoma, Encyonopsis, Fragilaria, Fragilariforma, Melosira, Navicula, Nitzschia, Stephanodiscus, Synedra, Tabellaria and Thalassiosira Cleve) we can conclude that more recent literature , followed by Pinnularia (12) . Of interest are the similarities and differences with the neo-tropical (South America) diatom flora as evidenced by the presence of Eunotiaenigmatica L.F. Costa & C.E. Wetzel and Encyonopsisfrequentis Krammer have been described from DR Congo, with a peak (51 taxa) at the end of the 1940\u2019s Krammer in DR Cost century (Eunotiapseudoflexuosa Hustedt, Nitzschiaelliptica Hustedt and Pinnulariatropica Hustedt. All three aforementioned species were described in a publication in which Hustedt described a total of 50 new taxa from the \u201cParc national Albert\u201d (Nitzschiaepiphyticoides Hustedt was thoroughly studied (It is worth noting that almost all of the new diatoms (see Table century as well Albert\u201d . Althoug studied it still studied ."} +{"text": "PLOS ONE team want to sincerely thank all of our Editorial Board Members, Guest Editors, and Reviewers for the journal in 2018. Your contributions of time and expertise support your research community, advance scientific progress, and continue to make PLOS ONE a leader in its field. This past year, PLOS ONE received the assistance of more than 8,000 Editorial Board members, 900 Guest Editors, and 53,000 Reviewers, who handled more than 36,000 manuscripts that resulted in 17,000 publications (PLOS and the ications .PLOS ONE and Open Science. Thank you all for your work!We\u2019re deeply grateful to all of our volunteers whose dedicated efforts support"} +{"text": "Viola betonicifolia (Violaceae) is commonly recognized as \u201cBanafsha\u201d and widely distributed throughout the globe. This plant is of great interest because of its traditional, pharmacological uses. This review mainly emphases on morphology, nutritional composition, and several therapeutic uses, along with pharmacological properties of different parts of this multipurpose plant. Different vegetative parts of this plant contained a good profile of essential micro- and macronutrients and are rich source of fat, protein, carbohydrates, and vitamin C. The plant is well known for its pharmacological properties, e.g., antioxidant, antihelminthic, antidepressant, anti-inflammatory, analgesic, and has been reported in the treatment of various neurological diseases. This plant is of high economic value. The plant has potential role in cosmetic industry. This review suggests that V. betonicifolia is a promising source of pharmaceutical agents. This plant is also of significance as ornamental plant, however further studies needed to explore its phytoconstituents and their pharmacological potential. Furthermore, clinical studies are needed to use this plant for benefits of human beings. Demand of medicinal plants is increasing day by day around the globe for improved quality of life ,2. In reThe family Violaceae is also known by different names such as Retrosepalaceae, Leoniaceae, and Alsodeiaceae. This family includes ~20 genera as well as 800 species . Viola iSome of the species of this genus are used to treat appendicitis, acute nephritis, hepatitis, snake bites, and bronchitis. Many species of this genus are exploited as traditional remedies in Russia, Korea, Romania, and Iran for the treatment of trophic ulcers, shingles, and diuretics and, while as anti-inflammatory agents for skin eruptions, rheumatism, bronchitis, and dermatitis in traditional medicines. The plants of this genus are used in landscape beautification because of splendid colors of flowers . This geV. betonicifolia comprehensively. It is a nutritive plant, and due to widely exploitation in folk medicine, enthused us to write review on this medicinal plant. We have comprehensively described its distribution, nutritional, and medicinal properties, together with its phytochemicals.As part of our studies of documenting the indigenous flora of Pakistan ,19,20,21Viola betonicifolia, nutrients, viola, antioxidant, antimicrobial, volatile, etc., to search electronic databases such as PubMed, Web of Science, Scopus, Science Direct, Scifinder, Google, and Google Scholar for information. Different relevant abstracts and all full text articles and books were consulted.Extensive literature survey was carried out with different keyword as Viola betonicifolia is recognized as Banafsha or Banfosha in Pakistan. It may be found in different habitats, including woodland, forest, shrubland, and herb fields -oct-3-ene (10%) [Chemical composition of different subfractions of the ne (10%) .V. betonicifolia could be investigated as a potential source of higher added value compounds for the nutraceutical industry as well as the food industry. However, further studies needed to explore the chemical constituents and their pharmaceutical potential. Further experimentation required to explore uses of this multipurpose plant in cosmetic industry as well.Medicinal treatments through the exploitation of plant-based natural compounds are widely investigated and numerous plants as well as herbs have been proclaimed already for their employments as analeptic. The higher nutritive value and functional characteristics, e.g., antioxidant, analgesic, antidepressant, antipyretic, anticonvulsant, and anti-inflammatory, linked to this plant recommend its exploitation in nutraceutics, medicines, and pharmaceutics. Henceforth, we corroborated that"} +{"text": "Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article. The purpose of this paper is to provide a comprehensive review of the chemical constituents of Zingiber officinale Roscoe. The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further applications of Zingiber officinale Roscoe. Zingiber officinale Roscoe is a perennial herb from the Zingiberaceae family, native to the Pacific Islands. It can be found in the Chinese provinces of Shandong, Henan, Hubei, Yunnan, Guangdong, Sichuan, and Jiangsu. ZOR is the fresh root of ginger, which is not only an important condiment but also one of the most commonly used Chinese medicines in clinical practice. Traditional Chinese medicine believes that ZOR has effects of releasing exterior and dissipating cold, arresting vomiting, resolving phlegm, and relieving coughs and can be used to treat fish and crab poison, stomach colds and vomiting, and cold sputum cough [um cough . Modern um cough \u20135. Due tum cough , toothpaum cough , and heaum cough \u201310.All development and utilization of ZOR are based on its material composition. The chemical composition of ZOR is complex, includes more than 300 types of species, and can be broadly divided into three categories: volatile oils, gingerol, and diarylheptanoids \u201313. In tVolatile oils, also known as ginger essential oils, are generally composed of terpenoids . Ginger Gingerol is the spicy component of ZOR. It is a mixture of various substances, all of which contain the 3-methoxy-4-hydroxyphenyl functional group. Gingerols can be divided into gingerols, shogaols, paradols, zingerones, gingerdiones, and gingerdiols, according to the different fatty chains connected by this functional group , 29. TheDiarylheptanoid is a group of compounds with 1,7-disubstituted phenyl groups and heptane skeletons in its parent structure. Currently, it can be divided into linear diphenyl heptane and cyclic diphenyl heptane compounds with antioxidant activity . The strZOR contains a variety of amino acids, including glutamate, aspartic acid, serine, glycine, threonine, alanine, cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, proline , 60, andZOR also contains polysaccharides , celluloZOR contains oxalic acid, tartaric acid, lactic acid, acetic acid, citric acid, succinic acid, formic acid, and malonic acid .ZOR has been shown to contain more than 20 inorganic elements such as K, Mg, Ga, Mn, P, Al, Zn, Fe, and Ba .\u03b2-sesquiphellandrene (18.4%), which were quite different from those of ginger grown in other regions. Another study showed the volatile oil content of ginger grown in five different areas of China was 0.13%, 0.23%, 0.30%, 0.14%, and 0.17% [\u03b2-citronellal, citral, geraniol, geranyl acetate, and zingiberene in mature ginger are lower than those in fresh ginger. The relative content of \u03b1-curcumene in mature ginger was higher than that in fresh ginger. In spicy gingerol compounds, the relative content of gingerol in mature ginger is higher than that in fresh ginger, which may be the result of further synthesis and accumulation of gingerol components in the process of continued growth of mature ginger in the second year [Various gingers have different regions and chemical compositions. Jolad conductend 0.17% , respectnd 0.17% , 65. Thend 0.17% . Mature ond year . The varond year .Ginger, as a kind of food and medicine, has many functions, such as antioxidant, anti-inflammatory, antimicrobial, anticancer, antiobesity, antidiabetic, antinausea, antiemetic, antiallergic, neuroprotective, hepatoprotective, cardiovascular protective, and respiratory protective activities . CurrentZOR is a widely used drug and food in clinical and daily life and has been used in the prevention and treatment of the digestive, circulatory, respiratory, and central nervous system diseases and other diseases. In this paper, the chemical constituents found in ZOR in recent years are summarized, and the results show that more than 300 chemical constituents are identified from the extracts of ZOR, including 194 types of volatile oil, 85 types of gingerol, and 28 types of diarylheptanoids compounds. From this, it can be clearly observed that ZOR has a complex chemical composition. The interactions between the components provide the clinical effects; therefore, it is necessary to further study the chemical composition and pharmacological action of ginger, for further applications. Exploring the mechanism by which different components perform the same effects is a new way to develop drugs in the future; for example, 4-terpineol and beta-sitosterol can act on the two targets of the 5-hydroxytryptamine receptor 3A and the mu-type opioid receptor, respectively, and provide corresponding therapeutic effects on diarrhea and dysentery. This can provide ideas for the research and development of new drugs and lay a foundation for further applications of ZOR."} +{"text": "Opoku NO, Bakajika DK, Kanza EM, et al. Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial. Lancet 392: 1207\u201316\u20142018; In this Article , the number of people who received ivermectin in 2014 should have been more than 110 million, and George Olipoh and Asare Sampson should have been included as authors rather than listed in the Acknowledgments section. These corrections have been made to the online version as of Oct 4, 2018. The printed Article is correct."} +{"text": "Each September, CDC, along with 3,000 global, national, regional, and local governments, as well as private and public health institutions, supports emergency preparedness efforts and encourages U.S. residents to take action before, during, and after an emergency. Every community in the United States needs to be ready to respond to an infectious disease outbreak, a chemical or radiologic release, or a natural disaster personal preparedness, 2) pandemic planning, 3) policy and partnerships, and 4) public health response. Personal preparedness helps communities to be more resilient in the event of an emergency. Through pandemic planning, CDC works to protect the nation from seasonal and pandemic influenza, and through partnerships, CDC plays a pivotal role in state and local readiness. CDC\u2019s Emergency Operations Center and the Division of State and Local Readiness bring together experts and state-of-the-art technology to detect and respond to public health emergencies, such as the recent Zika virus outbreak featured in this issue of"} +{"text": "These topics have been prolific since 1990 and before. Polymer science was prolific before, but its publication share declined in the recent two decades. Brazil, China, India, and South Korea have emerged as upcoming major contributors besides USA. Most prolific journals were Food Chemistry, Journal of Agricultural and Food Chemistry, Free Radical Biology and Medicine, and PLOS One. Clinical conditions with high citations included Alzheimer's disease, cancer, cardiovascular disease, and Parkinson's disease. Chemical terms and structures with high citations included alpha-tocopherol, anthocyanin, ascorbate, beta-carotene, carotenoid, curcumin, cysteine, flavonoid, flavonol, hydrogen peroxide, kaempferol, N-acetylcysteine, nitric oxide, phenolic acid, uric acid, vitamin C, vitamin E, selenium, and resveratrol. Citation patterns temporal analysis revealed a transition of the scientific interest from research focused on antioxidant vitamins and minerals into stronger attention focus on antioxidant phytochemicals (plant secondary metabolites).Antioxidants are abundant in natural dietary sources, and the consumption of antioxidants has a lot of potential health benefits. However, there has been no literature analysis on this topic to evaluate its scientific impact in terms of citations. This study is aimed at identifying and analysing the antioxidant publications in the existing scientific literature. In this context, a literature search was performed with the Web of Science database. Full records and cited references of the 299,602 identified manuscripts were imported into VOSviewer for bibliometric analysis. Most of the manuscripts were published since 1991. The publications were mainly related to the categories Antioxidants existed in many dietary natural sources such as vegetables, fruits, and beverages and dietary antioxidants such as flavonoids may help reduce the risk of mortality from coronary heart disease and incidence of myocardial infarction , 2. FurtTo understand the relevant key research categories in antioxidant researchTo identify the countries and journals having a major contribution to this research and to evaluate their citation performances during different time periodsTo reveal which chemicals/pharmaceuticals have had high citation counts during different time periodsTo show the overall impact of the antioxidant research, a bibliometric analysis of the antioxidant research field may allow a deep understanding of the changes in the field in terms of contributors and hot topics and their citation performance \u201313. To tIn May 2018, a literature search was performed with the multidisciplinary Web of Science (WoS) online database to identify papers with the following search strategy: TOPIC\u2009=\u2009(\u201cantioxida\u2217\u201d OR \u201canti-oxida\u2217\u201d). This strategy searched for papers that contain the word antioxidant/antioxidant and its derivatives in their title, abstract, or keywords. No restrictions were imposed on the publication year, publication type , or publication language.The manuscripts resulted from the literature search were evaluated and recorded for (1) publication year, (2) journal title, (3) total citation count, (4) authorship, (5) WoS category, and (6) manuscript type. The full records and cited references of these manuscripts were imported into VOSviewer for bibliometric analyses, such as citation performances of institutions, countries/regions, and journals.https://www.wordfrequency.info/free.asp?s=y). Supplementary data sheets in an Excel file , food science technology , and pharmacology/pharmacy . Four most prolific institutions have each accounted for 1% or nearly 1% of total publications, namely, the University of California , Chinese Academy of Sciences , Spanish National Research Council , and Council of Scientific and Industrial Research . Consistently, USA , China , and India were the leading countries in publishing antioxidant-related papers. Meanwhile, the most prolific journals that have each accounted for 1% or nearly 1% of total publications were Food Chemistry , Journal of Agricultural and Food Chemistry , Free Radical Biology and Medicine , and PLOS One .In overall, there were 258,450 (86.3%) original articles and 20,616 (6.9%) reviews in the analysed literature set. The remaining 6.8% of the publications included meeting abstracts, proceedings paper, and editorial material. Most of the publications were written in English . The publications were mainly classified into the WoS categories of In order to perform a systematic analysis and to better evaluate the importance of the research area for the scientific community worldwide, all the 299,602 identified publications were divided into four time periods/decades depending on their publication year, as follows: (i) 1990 and before, (ii) 1991\u20132000, (iii) 2001\u20132010, and (iv) 2011\u20132018.biochemistry/molecular biology , food science technology , polymer science , pharmacology/pharmacy , and chemistry, applied . The five most prolific countries/regions were USA , USSR , Japan , England , and Canada . The five most prolific journals were Journal of the American Oil Chemists' Society , Bulletin of Experimental Biology and Medicine , Federation Proceedings , Abstracts of Papers of the American Chemical Society , and Polymer Degradation and Stability . There were 4176 publications. In this earliest survey period, the publications were more evenly distributed into different WoS categories, with the five major categories being the Topics with high citations included carcinogenesis and lipid peroxidation . The mosbiochemistry/molecular biology has accounted for a larger share of publications . The four other major categories were pharmacology/pharmacy , endocrinology/metabolism , food science technology , and cell biology . Polymer science and chemistry, applied had much reduced share. The five most prolific countries/regions were USA , Japan , Germany , England , and Italy . Russia has much reduced share whereas Canada retained its share. The five most prolific journals were Free Radical Biology and Medicine , Journal of Agricultural and Food Chemistry , FASEB Journal , Free Radical Research , and Biochemical Pharmacology . There were 30,530 publications. During this period, the WoS category of N-acetylcysteine , ascorbate , beta-carotene , vitamin E , and alpha-tocopherol and atherosclerosis . Some no5; 65.2) .biochemistry/molecular biology has accounted for a smaller share of publications . The four other major categories were food science technology , pharmacology/pharmacy , nutrition/dietetics , and chemistry, applied . Chemistry, applied has regained its share compared to the previous decade. Meanwhile, polymer science continued to have a reduced share. The five most prolific countries/regions were USA , China , Japan , India , and Italy . The five most prolific journals were Journal of Agricultural and Food Chemistry , Free Radical Biology and Medicine , Food Chemistry , Free Radical Research , and Food and Chemical Toxicology . Food Chemistry began to become comparable with Journal of Agricultural and Food Chemistry with regard to publication count and citations per publication.There were 95,627 publications. Compared to the 1990s, the WoS category of Topics with high citations included nuclear factor erythroid 2-related factor 2 , Alzheimfood science technology has overtaken biochemistry/molecular biology as the largest WoS category for antioxidant papers. Pharmacology/pharmacy and chemistry, applied had similar share relative to the 2000s. Plant sciences have an uprising trend to take up the fifth spot in terms of the largest share of publications during 2011\u20132018. On the other hand, polymer science, once one of the five most prolific categories in 1990 and before, has maintained a small share in recent decades .There were 169,269 publications. For the first time in history, Food Chemistry , PLOS One , Journal of Agricultural and Food Chemistry , Molecules , and Free Radical Biology and Medicine . Food Chemistry has finally overtaken Journal of Agricultural and Food Chemistry as the largest journal in terms of publication count of antioxidant papers. Also, notable is the rise of PLOS One and Scientific Reports , two multidisciplinary journals that have published considerable number of antioxidant papers during this decade.China has overtaken USA as the most prolific country. The rest of the five most prolific countries/regions were India , Brazil , and South Korea . The five most prolific journals were Topics with high citations included autophagy , Parkinson's disease , atherosclerosis , carcinogenesis , and Alzheimer's disease . The mosfood science technology journals, with a leading example being Food Chemistry, has reflected that the attention is shifting towards dietary antioxidants.In overall, we have analysed nearly 300,000 publications on antioxidants that spanned over half a century. The results presented above have highlighted two polyphenols, curcumin and resveratrol, with high citations in the recent two decades. The potential health benefits of dietary curcumin and resveratrol have been discussed by the literature with a relevance to the control of redox signalling, inflammation, and autophagy , 18 and Manuscript related to the nuclear factor erythroid 2-related factor 2 (Nrf2) also attracted high citations. Nrf2 is a transcription factor essential for regulating homeostasis, cytoprotection, and innate immunity and plays an important role in activating the protective genes that are antioxidant and anti-inflammatory .The antioxidant research field has witnessed the increased publication share from China, India, and South Korea since the 2000s. Similar to the recently analysed ethnopharmacology and natural products publication fields, the contributions from Asian countries have been large, which could be partially explained by the notion that antioxidant assays require relatively less sophisticated equipment so that emerging research powers can also contribute comparable research volumes as traditionally established top research countries , 28.biochemistry/molecular biology, food science technology, and pharmacology/pharmacy. Brazil, China, India, and South Korea have emerged as upcoming major contributors to antioxidant research besides USA, which has been dominating the field for half a century. Most prolific journals were Food Chemistry, Journal of Agricultural and Food Chemistry, Free Radical Biology and Medicine, and PLOS One. Clinical conditions with high citations included Alzheimer's disease, cancer, cardiovascular disease, and Parkinson's disease. Chemicals with high citations included alpha-tocopherol, anthocyanin, ascorbate, beta-carotene, carotenoid, curcumin, cysteine, flavonoid, flavonol, hydrogen peroxide, kaempferol, N-acetylcysteine, nitric oxide, phenolic acid, uric acid, vitamin C, vitamin E, selenium, and resveratrol were published after 1991. Article to review ratio was 12.5\u2009:\u20091. The publications were mainly related to the categories veratrol . In resp"} +{"text": "The authors of \u201cA Community-Based Short Message Service Intervention to Improve Mothers\u2019 Feeding Practices for Obesity Prevention: Quasi-Experimental Study\u201d :e13828) wish to change the order of the authors on the publication so that Xu Qian is listed last.The previous order of authorship was as follows:Hong Jiang, Mu Li, Li Ming Wen, Louise Baur, Gengsheng He, Xu Qian, Xiaoying MaThe correct order of authorship is as follows:Hong Jiang, Mu Li, Li Ming Wen, Louise Baur, Gengsheng He, Xiaoying Ma, Xu QianAdditionally, the affiliations listed for author Gengsheng He have also been updated. Previously, only affiliation 2 was listed for this author:2Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, ChinaThe revised listing identifies that Gengsheng He is associated with affiliations 1 and 2:1School of Public Health, Global Health Institute, Fudan University, Shanghai, China2Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai, ChinaThe corrections will appear in the online version of the paper on the JMIR website on July 18, 2019, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article also has been resubmitted to those repositories."} +{"text": "After publication of this article , concernThe first author noted that the primary data underlying the results in Fig 3 are no longer available.PLOS ONE Editors retract this article due to concerns about the reliability and integrity of the results.In light of these issues, the RC, MLDB did not respond. AC, FB, IS, SD, DI did not agree with retraction. LM, VZ, PG, could not be reached."} +{"text": "Leachate generation is a major problem for municipal solid waste (MSW) landfills and causes significant threat to surface and groundwater. Samples were collected from the landfills of Iranian metropolises , Isfahan, Tabriz, Hamedan, Rasht, Sanandaj and Qazvin) based on the standard sampling methods and transferred to the laboratory. Cr, Cd, Hg, Pb, Ni, As, Ca, Mg, Fe, Mn, Na, K, Zn, Al, Ba, Li, Sr, Ti and V were analyzed. The pH values for the ten leachate samples obtained from 4.57 to 8.95. The results showed the amount of some metals in Iranian landfill sites higher than the DOE standards for agricultural irrigation and surface water. Specifications tableValue of data\u2022Based on the data, the amount of some metals in landfill leachate in Iranian landfill sites higher than the DOE standards for agricultural irrigation and surface water.\u2022Obtained data were used for assessment of soil, surface and ground water pollutions around the landfill sites.\u2022The results can be useful for wide application on leachate treatment plant.1anions, cations, metals and heavy metals were analyzed The data obtained from the pH analysis of leachates in ten sites are summarized in 2The leachate samples were prepared with the coordination of the waste management organization of Iranian metropolises from different cities. The criterion for selecting cities was determined with the geographic location of these cities in Iran, having a landfill, having leachate drainage. Also, the selected city must have an acceptable population and should be the provincial capital. The basis on this criteria, ten point selected of Iran , Qazvin, Rasht, Mashhad, Sanandaj, and Ahvaz)"} +{"text": "The correct Author Contributions statement appears below:\u201cZA, SS, BB, DW, JB, RV, and BA conducted the experiments. ZA, SS, BB, DW, JB, MM, NG, RV, AB, and BA analyzed and interpreted the data. ZA, SS, DW, JB, NG, MM, RV, AB, and BA helped to write and review the manuscript. ZA agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-019-46696-6, published online 15 July 2019Correction to: The original version of this Article contained an error in the name of the author Tyler O. Hughes, which was incorrectly given as Tyler Hughes.Additionally, in the original version of this Article, Affiliation 3 was incorrectly given as \u2018Department of Biology, Penn State University, Philadelphia, PA, USA\u2019. The correct affiliation is listed below.Department of Biology, The Pennsylvania State University, University Park, PA 16802, USAThis has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Also, it found that high-income cities have a higher technology gap than upper middle\u2013income cities, and media reports efficiency have a high correlation with respiratory diseases and CO2.Over the past few decades, China\u2019s rapid economic, energy, and industrial developments have caused serious environmental damage. However, as there are large resource, energy use, economic, and environmental damage differences across Chinese regions, the Chinese government is seeking to reduce city pollution across the country. Most previous analyses have only looked at these issues on a single level; for example, the impact of environmental pollution on health, or energy and environmental efficiency analyses, but there have been few studies that have conducted overall analyses. Further, many of the methods that have been used in previous research have employed one-stage radial or non-radial analyses without considering regional differences. Therefore, this paper developed a meta undesirable two-stage EBM DEA model to analyze the energy, environment, health, and media communication efficiencies in 31 Chinese cities, from which it was found that the productivity efficiency in most cities was better than the health treatment efficiencies, the GDP and fixed asset efficiency improvements were small, the air quality index (AQI) and CO The World Health Organization claims tPast studies have focused on the relationship between economic growth and air pollution ,5, the c2 and air quality index (AQI) to the environment. The undesirable output CO2 and AQI\u2014intermediate output from the production stage (first stage)\u2014can be seen in second stage\u2014input resources\u2014to the production of new values in the health treatment stage (second stage). The government provides health expenditures to reduce diseases caused by environmental pollution. Media reports can objectively present air pollution information, identify the causes of pollution in a timely manner, and identify protective measures so as to prevent or control the risk of physical injury and reduce the incidence of diseases. Media reports can reduce the incidence of public diseases, improve the public\u2019s physical and mental health, and improve the health and ethics of the entire population. So, government health expenditures and media reports can reduce disease. Therefore, energy, environmental pollution, health, and media can be constructed by the two-stage model.However, in general, few studies have linked these energy, air pollution, health discussions and media discourse. This article will therefore discuss economics, environmental pollution, health, and media together. The relationship is shown in While several past studies have employed network data envelopment analysis (DEA) to examine production and pollution controls ,42,43,442 emissions and AQI. Health treatment was taken as the second stage based on health expenditure and media report inputs and birth rate and respiratory disease prevalence outputs.As this model not only includes existing production efficiencies but also considers the sustainability of human health, it has two main contributions. First, to avoid under- or over-estimation, the economic, environmental, media communication, and health efficiencies are jointly analyzed. Second, a meta undesirable two stage EBM DEA model is used to avoid the radial and non-radial biases. Sometimes, decision making units (DMUs) are not homogeneous and have different resource endowments, such as income and location, which affects the inputs and outputs of DMUs, so the concept of meta should therefore be adopted to avoid large regional difference by grouping DMUs. Data from 2013\u20132016 for 31 Chinese cities were extracted and analyzed, with production taken as the first stage based on labor, fixed assets, and energy consumption inputs and GDP output, with the link between the production stage and the health treatment stage variables being COPast research can be divided into discussions on the relationships between economic growth and air pollution and between air pollution and human health, examinations of preventative measures to reduce the effects of air pollution on societal health, and the effect of public awareness raising by the media on air pollution and environmental issues.3 over a 24-h average particulate matter PM2.5 increased the risk for wheezing bronchitis by 5%. In related studies, Chen et al. [2, PM10, and O3. In examinations on the effects of long-term exposure to air pollutants on human health, Loomis et al. [3 increase in PM10 and NO2 was significantly associated with non-accidental mortality. In other studies, Kelly and Fussel [With a focus on economic growth and air pollution, Georgiev and Mihaylo found thn et al. used GLMn et al. examineds et al. found a s et al. revieweds et al. studied d Fussel analyzedd Fussel found th3, the cardiovascular mortality increased by 0.47% and the respiratory mortality increased by 0.57%, when PM10 increased by 10\u03bcg/m3, cardiovascular mortality increases by 0.27% and respiratory mortality increased by 0.56%, and that short-term exposure to a particulate environment was associated with an increased incidence of cardiopulmonary disease and an increased mortality in low- and middle-income countries. Zigler et al. [Khafaie et al. used resr et al. exploredr et al. found thTo reduce the effects of air pollution on societal health, Torretta et al. proposedNew York Times, the Los Angeles Times, and the Washington Post over 20 years and found that air pollution was generally explained as being related to asthma. However, the newspapers avoid connecting respiratory disease with environmental problems that reduced the government\u2019s control on air pollution due to low public concern. Elliot et al. [In a study on the relationship between media promotion and air pollution, Dworkin and Pijwaka exploredt et al. studied t et al. investigt et al. studied t et al. studied t et al. examinedt et al. studied The theoretical framework for this study is based on previous study results and the following assumptions: public media reports positively impact public awareness of air pollution and its impact on the environment and human health.Based on the above literature analysis, this paper makes the following research hypotheses:H1: Public media reports have a correlation with CO2 and AQI.H2: Public media reports have a correlation with respiratory diseases.As can be seen from this brief literature review, much of the previous research has only been on a single level using radial and non-radial methods with little consideration for regional differences. Therefore, to overcome these issues, this paper used a meta undesirable two-stage EBM DEA model to explore the energy, environment, health, and media communication efficiencies in 31 mainland Chinese cities. Due to the difference in income between regions, this paper compares the 31 Chinese cities divided into high- and upper middle\u2013income cities. The hypotheses are as follows:H3: In the efficiencies, high-income cities are higher than upper middle\u2013income cities.H4: In the Technology gap, high-income cities are higher than upper middle\u2013income cities.After Farrell proposedIn 2007, F\u00e4re et al proposedWhile the EBM DEA resolved the radial and non-radial issues, it failed to deal with the two-stage problem, and while the NDEA model solved the multi-stage problems, it failed to deal with the radial and non-radial problems. As different countries have different social and cultural backgrounds, economic environments, management models, and production efficiencies, and as manufacturers from different countries have different production technologies, if a traditional DEA assumes that all DMUs have the same technical level in the efficiency evaluation, it may be inappropriate to analyze efficiencies using traditional efficiency evaluation models. This paper, therefore, proposes a model based on Tone and Tsutsui , O\u2019Donne2 emissions and AQI. In the second stage, health expenditure and media reports were the input, with the output being birth rate and respiratory diseases. As respiratory diseases were seen as undesirable output, Tone and Tsutsui\u2019s [This study collected data from 31 Chinese cities. In the first stage, labor, fixed assets, and energy consumption were the inputs, and GDP was the output, with the one-stage and two-stage links being COsutsui\u2019s EBM modeIn a traditional DEA efficiency evaluation, it is usually assumed that all producers have the same level of production technology; however, in reality, most decision-making units have different production technologies because of different geographical locations, national policies, or social and economic conditions. Battese and Rao and Battn DMU and K division, jDMU = , m input jX = , s output, jY = , DMU efficiency: Due to management, resource, regulatory, and environmental differences, all firms (N) are made up of DMU groups (1 + N2 +\u2026+ NGN = N), with Xij and Yrj denoting the input and with the final output being r for unit j . Under the meta-frontier, DMU k then chooses an optimal final output weight to attain the highest efficiency; therefore, under a non-oriented EBM, the efficiency of DMU k using the meta undesirable two stage EBM DEA can be determined using the following linear programming.Subject toY: DMU output,X: DMU input,From the above equations, the overall technological efficiency of the cities can be determined under the meta-frontier, and using Equation (1)\u2013(5), the overall technological efficiency of all high-income and upper middle\u2013income cities can be determined under the meta-frontier undesirable two-stage EBM group frontier modelThe high- and upper middle\u2013income cities were divided into g decision-making units, each of which was assigned an optimal output weight; therefore, the DMU efficiency under the group frontier was solved using the following equations.Subject toAs the production frontier for the g groups were included in the meta-frontier, the technical efficiency under the meta-frontier needed to be less than the technical efficiency under the group frontier. The ratio of the two frontiers is called the technology gap ratio (TGR):The Hu and Wang total-faIf the target fixed assets, labor, energy consumption, and health expenditure inputs equaled the actual inputs, then the fixed assets, labor, energy consumption, health expenditure, and media efficiencies equaled 1, indicating overall efficiency. If the target fixed assets, labor, energy consumption, health expenditure, and media inputs were less than the actual inputs, then the fixed assets, labor, energy consumption, health expenditure, and media efficiencies were less than 1, indicating overall inefficiency.If the target GDP and birth rate desirable outputs were equal to the actual GDP and birth rate desirable outputs, then the GDP and birth rate efficiencies equaled 1, indicating overall efficiency. If the actual GDP and birth rate desirable outputs were less than the target GDP and birth rate desirable outputs, then the GDP and birth rate efficiencies were less than 1, indicating overall inefficiency.2, and AQI undesirable outputs were equal to the actual respiratory disease, CO2, and AQI undesirable outputs, then the respiratory diseases, CO2 and AQI efficiencies equaled 1, indicating efficiency. If the target respiratory disease, CO2, and AQI undesirable outputs were less than the actual respiratory disease, CO2, and AQI undesirable outputs, then respiratory diseases, CO2, and AQI efficiencies were less than 1, indicating inefficiency.If the target respiratory diseases, COBased on the World Bank\u2019s classification for rich and poor countries, the 31 Chinese cities were divided into high- and upper middle\u2013income cities, with the upper middle\u2013income economies having a GNI per capita between $3896 and $12,055, and the high-income economies having a GNI per capita of $12,056 or more .Therefore, the 31 sample cities were divided into 14 high-income cities and 17 upper middle\u2013income cities .2 and AQI are undesirable outputs . In theh et al. , input ig et al. . The twoThe variables used in the study are explained in the following:First stage: production stageLabor input: Employees; this study used the number of employed people in each city at the end of each year; unit: person.Energy consumption was calculated from the total energy consumption in each city; unit: 100 million Tonnes.Fixed assets: the capital stock in each city was calculated using the fixed assets investment in each city; unit: 100 million CNY.Input variables:Output variables:Desirable output (GDP): the GDP in each city was used as each city\u2019s output; unit: 100 million CNY;2, a common greenhouse gas;Carbon dioxide: CO2), and nitrogen.AQI: the air quality index, which is a measured concentration of the pollutants such as PM2.5, PM10, sulfur dioxide , with the number of statistics being the total amount in the year. The official news websites were selected because of the amount of news published and their wide influence.Input variables:2. Karimi et al. [3, PM2.5, PM10, NO2, NOx, SO2, and CO) were associated with increased mortality and hospitalization rates, but PM2.5 and PM10 were more strongly affected.Respiratory Diseases: referring to the prevalence of respiratory diseases. In order to examine the effects of medical health inputs on diseases in various regions, only respiratory disease data can be collected, and data on specific respiratory diseases cannot be obtained. Therefore, in this study, the respiratory disease rate was used to measure the adverse effects of air pollutants and the effects of health management, mainly because a large amount of literature research has been proved. Some researchers had found that respiratory disease is significantly affected by air pollutants as PM10 . In some model specifications, ozone, another measure of pollution, is also found to affect respiratory illness. Furong et al. studied i et al. collecte2, had significant effects on female fertility and infant birth rate.Birth rate: this study used the infant birth rate as the second output indicator for medical input. Carr\u00e9 exploredOutput variables:The average value of the undesirable carbon dioxide emissions fell in 2016, the maximum dropped in 2015, and then rose again in 2016. The maximum and average AQI reached its highest point in 2013 and then continuously declined. The minimum value decreased in 2016 but was slightly smaller compared with the maximum.The maximum respiratory disease efficiency continued to rise, and the average value decreased in 2015 and increased slightly in 2016. The birth rate efficiency was the highest, with both the minimum and average showing a continuous slow rise. The standard deviation reached a high in 2015 and declined slightly in 2016.After reaching a peak in 2013, the maximum, minimum, and average news report efficiencies continued to decline and dropped significantly to the lowest point in 2014. From 2013, when mainland China began to disclose the annual AQI data in each region, the media attention on air pollution began to decline, and the reports decreased.In Chengdu and Shijiazhuang had efficiency fluctuations, with Chengdu\u2019s fluctuating below 0.6 for all four years, and with Shijiazhuang\u2019s being below 0.5 and having a downward trend.Five cities had efficiencies above 0.8 for three years, and four cities had efficiencies between 0.5 and 0.8 for four years. Nanning\u2019s efficiency was 1 in three years, which fell slightly in 2016 to around 0.9. Beijing achieved an efficiency of 1 in 2013, after which it began to decline, reaching its lowest value in 2015 at 0.8.In the production stage, there were annual efficiencies of 1 only in Guangzhou, Lhasa, and Shanghai in all four years, and in the treatment stage, there were annual efficiencies of 1 in Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai.Beijing, Changchun, Changsha, Chengdu, Harbin, Hangzhou, Hefei, Hohhot, Jinan, Nanchang, Nanjing, Shenyang, Tianjin, Wuhan, and Zhengzhou had higher efficiency scores in the production stage than the treatment stage, and Chongqing, Guiyang, Haikou, Kunming, Lanzhou, Nanning, Shijiazhuang, Taiyuan, Urumqi, Xi\u2019an, Xining, and Yinchuan had higher efficiency scores in the treatment stage than the production stage.Chongqing, Guiyang, Kunming, Lanzhou, Shijiazhuang, Taiyuan, Xining, and Yinchuan had four-year production stage efficiencies below 0.6, with the poorest being in Shijiazhuang, with four-year efficiencies of around 0.4. All other cities had efficiencies between 0.4 and 0.6.The worst performing cities in the treatment stage were Chengdu and Tianjin, with Chengdu having an efficiency of less than 0.4 in three years; therefore, there was a significant need for improvement.The declines in the production stage were much smaller than in the treatment stage, with the largest being in Nanchang, which fell from 0.85 in 2013 to 0.66 in 2016. Efficiency changes in the treatment stage were more volatile, with Beijing and Wuhan having the largest declines, from 1 in 2013 to 0.6 in 2016.The efficiency increases in both the production and treatment stages were much the same. Changsha, Hefei, Jinan had the largest increases, with Jinan rising from 0.47 in 2013 to 1 in 2016 and Hefei rising from 0.48 in 2013 to 1 in 2016.In In production stage, according to the Wilcoxon Test, the efficiency of the high-income and upper middle\u2013income countries from 2013 and 2015 is strong significant. The efficiency of the 2014 and 2016 production stages is not significant, but the efficiency of the 2013 and 2015 production stages is strongly significant. The efficiency values of high-income countries are higher than those of upper middle\u2013income countries, consistent with the H3 hypothesis in 2013 and 2015.In treatment stage, Wilcoxon Test shows that the efficiency of high-income and upper middle\u2013income countries from 2013 and 2015 is strongly significant. The efficiency of the treatment stage in 2014 and 2016 is not significant, but the efficiency of the treatment stage in 2013 and 2015 is strongly significant. The efficiency values of high-income countries are higher than those of upper middle\u2013income countries, consistant with the H3 hypothesis in 2013 and 2015.Only Guangzhou, Lhasa, and Shanghai had fixed assets efficiencies of 1 in all four years; however, Beijing, Haikou, Nanning, and Urumqi all had annual efficiencies higher than 0.8. The other 24 cities had a significant need for improvement. For example, Changsha, Chongqing, Guiyang, Hefei, Kunming, Nanchang, Nanning, Shijiazhuang, Tianjin, Xi\u2019an, and Yinchuan all had efficiencies under or around 0.6, with Tianjin requiring the most improvements at only 0.45 in 2013.Guangzhou, Lhasa, Nanning, and Shanghai had energy consumption efficiencies of 1 in all four years, and Beijing, Changchun, Fuzhou, Harbin, Haikou, Hefei, Nanchang, Urumqi, and Zhengzhou all had efficiencies higher than 0.8. However, Guiyang, Lanzhou, Shijiazhuang, Taiyuan, Xining, and Yinchuan had efficiencies lower that 0.6, with the worst performance being in Taiyuan, at below 0.2, followed by Shijiazhuang, Lanzhou, and Yinchuan at around 0.4.Only Guangzhou, Lhasa, and Shanghai had labor efficiencies of 1 for all four years, and the worst performing cities were Chongqing, Guiyang, Kunming, Lanzhou, Shijiazhuang, Taiyuan, and Xining at below 0.7 in most years. All other cities had labor efficiencies between 0.8 and 0.9.Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had carbon dioxide emissions efficiencies of 1 in all four years. However, Lanzhou, Taiyuan, and Yinchuan all scored less than 0.4, with all of Taiyuan\u2019s results below 0.2. Changchun, Harbin, Hefei, Nanchang, Urumqi, and Zhengzhou had carbon dioxide emissions efficiencies higher than 0.8, and the other cities had carbon dioxide emissions efficiencies between 0.6 and 0.8.There were also large differences in the AQI efficiencies. Beijing. Chongqing, Fuzhou, Guangzhou, Haikou, Kunming, Lhasa, Nanjing, Nanning, Shanghai, and Urumqi had AQI efficiencies of 1 in all four years, and many cities had two- or three-year efficiencies of 1, with the other years being above 0.9. However, the AQI efficiencies in Lanzhou, Taiyuan, Xining, and Yinchuan began to decline from 2013 and, by 2016, had fallen to around 0.4. The largest declines were in Lanzhou, Nanchang, Shijiazhuang, Taiyuan, Wuhan, Xi\u2019an, Xining, Yinchuan, and Zhengzhou, but there were AQI efficiency increases in Changchun, Chengdu, Harbin, Hefei, Jinan, Urumqi, and Shenyang.2 emissions and AQI efficiencies in most cities. Guangzhou, Lhasa, and Shanghai had GDP efficiencies of 1, and the GDP efficiencies in Beijing and Nanning in the first three years were all 1, but both declined slightly in 2016. Guiyang, Kunming, Lanzhou, Shijiazhuang, Taiyuan, and Xining had comparatively poor efficiencies at lower than 0.8, and all other cities had GDP efficiencies between 0.8 and 1.The GDP efficiencies were better than the COFuzhou, Guangzhou, Haikou, Lhasa, Nanning, Shanghai. Beijing, Changsha, Urumqi, Xining, and Yinchuan had health expenditure efficiencies of 1 or at least two years above 0.9. However, Zhengzhou\u2019s health expenditure efficiency in all four years was below 0.5, and Tianjin had a health expenditure efficiency less than 0.2 for three years. There were noticeable health expenditure efficiency volatilities. However, 13 cities had reduced efficiencies and needed improvements.Fuzhou, Guangzhou, Haikou, Lhasa, Nanjing, and Shanghai had birth rate and respiratory diseases efficiencies of 1, but Chengdu, Harbin, Shijiazhuang, and Tianjin had four-year efficiencies just above 0.7.Compared with the birth rate efficiency, the respiratory diseases efficiencies required significant improvements. Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had respiratory disease efficiencies of 1, Chengdu and Tianjin had respiratory disease efficiencies of around 0.6, and Harbin and Shenyang had three-year efficiencies between 0.7 and 0.8. Nine cities had reduced efficiencies, and 17 cities had rising efficiencies.2 and AQI efficiency exceeded 0.4 , and there is a high correlation, which is consistent with the H1 hypothesis. The correlation coefficient between Media efficiency and Respiratory Diseases efficiency is 0.5932 , which is correlated and conforms to the H2 hypothesis.According to 2 and AQI efficiency are 0.4275 and 0.3387 , and there is a high correlation, which is consistent with the H1 hypothesis. The correlation coefficient between Media efficiency and respiratory diseases efficiency is 0.4252 , which is correlated to and conforms to the H2 hypothesis.In 2014, the correlation coefficient between media efficiency and CO2 and AQI efficiency exceeded 0.4 , and there is a high correlation, which is consistent with the H1 hypothesis. The correlation coefficient between media efficiency and respiratory diseases efficiency is 0.5751 , which is correlated to and conforms to the H2 hypothesis.In 2015, the correlation coefficient between media efficiency and CO2 and AQI efficiency exceeded 0.4 , and there is a high correlation, which is consistent with the H1 hypothesis. The correlation coefficient between media efficiency and respiratory diseases efficiency is 0.3697 , which is correlated and conforms to the H2 hypothesis.In 2016, the correlation coefficient between media efficiency and COChengdu, Chongqing, Nanchang, Shijiazhuang, and Taiyuan had technology frontiers of 0.7, which fell in Nanchang, Shijiazhuang, and Taiyuan. However, the technology frontier in the other cities was mostly between 0.8 and 0.9.Changsha, Chengdu, Chongqing, Fuzhou, Hangzhou, Hefei, Jinan, Kunming, Nanjing, Shenyang, Wuhan, Urumqi, and Zhengzhou had rising technology frontiers, but they fell in the other 15 cities, indicating that the technology gap between the cities was expanding, which is in line with the economic development and technical level characteristics in mainland China.Fuzhou, Hefei, Jinan, Kunming, Shenyang, Wuhan, Urumqi, and Zhengzhou had rising technology frontiers during the production stage, but those of the other cities fell, further indicating that the technology gap between the regions was expanding. For example, while Harbin, Hohhot, Jinan, Nanchang, Shenyang, and Zhengzhou had higher technology gaps compared to cities in their regions, there was still a large gap compared with other cities in the country. Only Beijing and Shijiazhuang had declining technology gaps; however, the scores in the other 23 cities all rose, indicating that the technology gap between the regional cities in the treatment stage in most cities shrank.According to the Wilcoxon Test in In production stage, Wilcoxon Test shows that the technology gap of strong-income and upper middle\u2013income countries from 2013 to 2016 is strongly significant. In other word, the technology gap of high-income countries is higher than that of upper middle\u2013income countries, consists with the H4 hypothesis.In the treatment stage, the Wilcoxon Test shows that the technology gap of high-income and upper middle\u2013income countries is strongly significant from 2013 to 2016, where the technology gap of the 2014 treatment stage is weakly significant. The treatment stages in 2013, 2015, and 2016, technology gap is strongly significant. The technology gap of high-income countries is higher than that of upper middle\u2013income countries, consistent with the H4 hypothesis.This study used panel data and a meta undesirable two-stage EBM DEA to examine the production and health governance efficiencies in 31 Chinese provincial capital cities from 2013 to 2016 under the influence of media reports and the technology gap between high-income and middle-income cities.Guangzhou, Lhasa, and Shanghai had overall efficiencies of 1. Beijing\u2019s overall efficiency score was only 1 in 2013 but was lower in other years, and the other 20 cities had four-year efficiency scores between 0.5 and 0.8; therefore, most cities needed efficiency improvements.Guangzhou, Lhasa, and Shanghai had annual efficiencies of 1 in the production stage, and Fuzhou, Guangzhou, Haikou, Lhasa Nanning, and Shanghai had annual efficiencies of 1 in the treatment stage. Overall, 15 cities had higher efficiencies in the production stage than in the treatment stage, and 12 cities had higher efficiencies in the treatment stage than in the production stage. Chongqing, Guiyang, Kunming, Lanzhou, Shijiazhuang, Taiyuan, Xining, and Yinchuan had four-year production stage efficiencies below 0.6, with the poorest being Shijiazhuang, with a four-year efficiency of around 0.4. Chengdu and Tianjin had the poorest treatment efficiencies; however, in general, the treatment stage and production stage efficiencies were similar.Guangzhou, Lhasa and Shanghai had fixed assets efficiencies of 1 in all four years, but 11 cities had four-year fixed assets efficiencies of only about 0.6, with Tianjin, which had a four-year efficiency of below 0.45, requiring the most improvement. Guangzhou, Lhasa, Nanning, and Shanghai had energy consumption efficiencies of 1 in all four years, nine cities had efficiencies higher than 0.8, and the lowest efficiency was in Taiyuan, at below 0.2. Guangzhou, Lhasa, and Shanghai had labor efficiencies of 1, and only seven other cities had labor efficiencies below 0.7 in most years.Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had carbon dioxide emissions efficiencies of 1 in all four production stage years, but the other 25 cities had carbon dioxide emissions efficiencies of less than 0.4 in all four years, of which Taiyuan had the lowest, at less than 0.2. Only Beijing had an AQI efficiency of 1 in all four years, and Chongqing, Fuzhou, Guangzhou, Haikou, Kunming, Lhasa, Nanjing, Nanning, Shanghai, and Urumqi had two- or three-year efficiencies of 1, with the other years being higher than 0.9. However, in most cities, the AQI efficiencies had large fluctuations, with eight cities fluctuating upward. Even though only three cities achieved GDP efficiencies, the efficiencies were relatively good in most cities, at close to 0.8.Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had media report efficiencies of 1 in all four years, and the efficiencies in 17 cities ranged from 0.5 to 0.9 in most years. However, Lanzhou and Xining\u2019s highest annual efficiencies were only about 0.4. The media report efficiencies fluctuated significantly, and many cities experienced large declines, with the largest being in Beijing.Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had four-year health expenditure efficiencies of 1. However, Tianjin had the worst performance, with its health expenditure efficiency in three-years being below 0.2. The health expenditure efficiencies in the other cities fluctuated significantly, and many cities experienced large declines, with the largest being in Beijing. The urban birth rate efficiency improvements were small; however, Chengdu, Harbin, Shijiazhuang, and Tianjin had the lowest four-year efficiencies at above 0.7.The respiratory disease efficiencies required in most cities needed significant improvements, and the efficiency differences between the cities was wide. Fuzhou, Guangzhou, Haikou, Lhasa, Nanning, and Shanghai had four-year respiratory disease efficiencies of 1. Chengdu and Tianjin had low efficiencies of around 0.6 in most years. Nine cities had four-year efficiency fluctuations or declines, and the other 17 cities had upward fluctuations or continuous upward trends. Overall, the respiratory disease efficiencies improved.respiratory diseases, AQI, and CO2 efficiency.The media reports efficiency has a high correlation with Guangzhou, Lhasa, and Shanghai had technology frontiers of 1, but Chengdu, Chongqing, Nanchang, Shijiazhuang, and Taiyuan had large technology gaps. Changsha, Chengdu, Chongqing, Fuzhou, Hangzhou, Hefei, Jinan, Kunming, Nanjing, Shenyang, Wuhan, Urumqi, and Zhengzhou had rising technology frontiers, but the technology frontiers in the other 15 cities fell.Fuzhou, Guangzhou, Guiyang, Haikou, Lhasa, Nanjing, and Shanghai had treatment stage technology frontiers of 1. However, Harbin, Hohhot, Jinan, Nanchang, Shenyang, and Zhengzhou had backward technology frontiers. Beijing and Shijiazhuang had sustained fluctuating technology frontiers, and the technology frontiers in the other 23 cities all rose, indicating that the technological differences in the treatment stage shrank. Also, we found that high-income cities are higher technology gap than upper middle\u2013income cities.The main conclusions from this study were as follows:From these results, the following policy recommendations are given.As there were obvious differences between the cities, cooperation between regions should be actively promoted. The technology gap of high-income countries is higher than that of upper middle\u2013income countries. So, high-income cities have technological advantages and rich experience in air pollution and health management. High-income cities can use advanced technologies for air pollution treatment by combining regional characteristics, economic and social development levels, geographical characteristics of cities, and meteorological conditions.Industrial structure and energy structure adjustments need to be more rapidly implemented to improve the production and environmental efficiencies in the Beijing-Tianjin region. The Beijing-centered Beijing-Tianjin region had lower production and treatment stage efficiencies than the Pearl River Delta area with Guangzhou at the center and the Yangtze River Delta area with Shanghai at the center. Therefore, the energy consumption, fixed assets investment, human resource input, and environmental efficiencies need to be improved in Beijing. The economic and energy structures in the Beijing-Tianjin region are closely related, and the economic growth in the region has relied heavily on coal for its energy production. Therefore, there needs to be a greater focus on energy structure adjustments and clean energy and clean coal\u2013use technological developments to replace coal and maintain production. Developing and maintaining normal economic and social development is also an important treatment measure.The media is an important \u201clink\u201d and \u201cbridge\u201d for the dissemination of health information. It plays an irreplaceable role in reporting health knowledge, changing health concepts, and promoting healthy behavior. The media has strengthened coverage of air pollution, energy conservation and emission reduction, green development, and environmental protection in terms of content and channels. By continuously improving the scientific and professional reporting of the media, this can guide the public to rationally think about and interpret information and improve the accumulation of public health knowledge. On the other hand, it eliminates public fears and threats of air pollution and promotes public health awareness. Therefore, it is important to enhance the strategy of media coverage. In order to increase the effect of media reporting on public health, media organizations need to constantly improve and strengthen reporting strategies. The media needs to strengthen reports on air pollution, energy conservation, green development, and environmental protection in terms of content, channels, and forms of communication and needs to improve the science and professionalism of the reporting that guides the public to think about and interpret information rationally.Drawing on the advanced health management efficiency in the Pearl River Delta and the Yangtze River Delta, the government can enhance the health management efficiency in the Beijing-Tianjin region. Health management investment in the Beijing-Tianjin region needs to continue to increase in line with economic growth and social development. The Beijing-Tianjin region still needs to strengthen its overall management, improve governance, and design more effective systems to improve health management efficiency.The governance in the middle-income cities needs to adopt strategies and measures appropriate to the regional characteristics. Middle-income cities in the west, such as Lanzhou, Xining, and Yinchuan, need to strengthen their industrial and energy structure adjustments. The news reporting efficiencies in these cities also need significant improvement. Therefore, systems need to be developed that are more suitable to the energy, economic, social, environmental and news reporting characteristics in these cities.To improve their production efficiency and environmental efficiencies, middle-income cities in the midwest and some individual middle-income cities in the East need to learn from the advanced technologies in cities such as Guangzhou and Shanghai.Middle-income cities in the northeast and some central cities need to improve their news report and health governance efficiencies. Therefore, these cities could learn from the governance measures adopted in other cities to improve the effectiveness of their news reports to increase the environmental awareness of their residents."} +{"text": "Author Contributions statement misrepresents the contributions of TN-J, KN, TW, TA, WG, and UH.In the original article, there was an error. The Author Contributions:A correction has been made to \u201cTN-J contributed to the conception and design of the study, and supervised data acquisition, analysis, and interpretation, as well as manuscript proofreading. LM, MS, and AN conducted informed consent. WG arranged MRI settings. KN, TW, and VK performed analysis of the MRI data. KN contributed to data acquisition, analysis, interpretation, and wrote the manuscript. CH contributed to data acquisition. TW, TA, WG, and UH contributed to manuscript proofreading.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Swiss Journal of Economics and Statistics (SJES) is a peer-reviewed journal that targets an international audience, and publishes original theoretical and empirical work in any field of economics. SJES also welcomes work that surveys the state of knowledge on a particular topic, or makes other people\u2019s work accessible, and publishes keynote lectures given at conferences organized by the Swiss Society of Economics and Statistics (SSES) or its members. Founded in 1867, SJES is owned and supported by the SSES. The journal originally accepted articles in English, French, Italian, or German, but, since 2006, accepts submissions only in English. SJES particularly welcomes contributions from early-career researchers.The The journal\u2019s day-to-day operations are managed by a team of co-editors: Martin Brown, Volker Grossmann, Rafael Lalive, and C\u00e9dric Tille. A board of associate editors supports the co-editors in strategic questions related to the journal: Iwan Barankay, Iris Bohnet, Mike Burkart, Jean-Pierre Danthine, Jordi Gali, Simon G\u00e4chter, Urban Jermann, Guido Kursteiner, Andreas M\u00fcller, Ugo Panizza, Rene Stulz, and Beatrice Weder di Mauro.Articles submitted to the journal are assigned to a handling co-editor who screens the paper to ensure it fits with the journal\u2019s aims and scope. The co-editor desk-rejects articles which have very low chances of a positive outcome or suggests a transfer to other journals. Articles selected for peer-review are sent to two anonymous external referees, who assess the paper\u2019s novelty, importance, and validity. Based on the reviewer\u2019s reports, the handling co-editor takes a first round decision. SJES is committed to a high-quality, efficient review process with a first round response time of about 2\u00a0months.Starting in 2018, SJES publishes with SpringerOpen, the open access portfolio of Springer Nature, ensuring visibility of accepted work. The SSES fully subsidizes the processing charge for accepted papers. All articles are published online immediately after acceptance and production. SJES is indexed in RepEC and places in the top tier of all RepEC journals, based on the impact factor for the last 10\u00a0years. Articles of particular relevance for economic policy in Switzerland are selected and disseminated in Die Volkswirtschaft/La Vie \u00e9conomique, a German and French language journal.SJES publishes three invited articles this month, based on keynote lectures given at the 2017 annual conference of the SSES in June 2017. Marion Fourcade (UC Berkeley) dissects the superiority of economists in economic policy advice. Aymo Brunetti (University of Berne) outlines what it takes to give policy advice and where the challenges are. Monika B\u00fctler, the former president of the SSES, comments on the two keynote lectures and provides her own point of view.SJES publishes two regular contributions this month in Springer Open. Philippe Bachetta (University of Lausanne) provides a macroeconomic assessment of the Sovereign Money Initiative in Switzerland. Arun Advani (University of Warwick) provides a review of methods to identify Linear Network Models.Co-EditorsMartin Brown, University of St. Gallen, SwitzerlandVolker Grossmann, University of Fribourg, SwitzerlandRafael Lalive, University of Lausanne, SwitzerlandC\u00e9dric Tille, Graduate Institute Geneva, SwitzerlandAssociate EditorsWharton School of the University of Pennsylvania, USAIwan Barankay, Harvard University, USAIris Bohnet, London School of Economics, UKMike Burkart, Paris School of Economics, FranceJean-Pierre Danthine, CREI, SpainJordi Gali, University of Nottingham, UKSimon G\u00e4chter, Wharton School, USAUrban Jermann, University of Maryland, USAGuido Kursteiner, Columbia Business School, USAAndreas M\u00fcller, Graduate Institute Geneva, SwitzerlandUgo Panizza, Ohio State University, USARene Stulz, University of Mainz, GermanyBeatrice Weder di Mauro,"} +{"text": "Scientific Reports 10.1038/s41598-019-41019-1, published online 13 March 2019Correction to: The original version of this Article contained an error in the spelling of the author Nagayoshi Katsuta, which was incorrectly given as Katsuta Nagayoshi. In addition, the Article contained an error in Affiliation 3, which was incorrectly given as \u2018Department of Education, Gifu University, Gifu, Japan\u2019. The correct affiliation is listed below:Faculty of Education, Gifu University, Gifu, JapanThese errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Asthma is a chronic inflammatory disease characterized by recurrent airway obstruction, airway hyperresponsiveness (AHR), airway inflammation, and airway remodeling, which is often associated with allergy and allergic rhinitis. Many patients with asthma are poorly controlled by current drug treatment, particularly a subgroup of patients with difficult\u2010to\u2010treat severe asthma, characterized by chronic symptoms, severe exacerbations, progressive loss of lung function, and resistance to corticosteroids. New therapeutic options are therefore highly warranted.l\u2010arginine to l\u2010ornithine and urea. Arginase is also expressed in nonhepatic tissues, including the airways. Two isoforms have been identified, arginases 1 and 2, which are encoded by different genes and are differentially expressed in the body.Our patent covers arginase as a new drug target for the treatment of asthma and/or allergic rhinitis, making use of an arginase inhibitor.l\u2010arginine is also substrate for constitutive and inducible nitric oxide synthases (cNOS and iNOS) yielding l\u2010citrulline and NO, one biological function of extrahepatic arginase may be regulating NO levels through competition with NOS for their common substrate\u2212) by particularly inflammation\u2010induced iNOS, by reduced bioavailability of l\u2010arginine to these enzymes. Moreover, increased arginase activity increases the production of l\u2010ornithine and its downstream products polyamines and l\u2010proline, which may be involved in airway remodeling by inducing cell proliferation, and enhanced collagen production and fibrosis, respectivelySince S)\u2010amino\u20106\u2010boronohexanoic acid (ABH) considerably reduces the airway sensitivity to inhaled allergen and protects against allergen\u2010induced early and late asthmatic reactions, AHR after these reactions, and airway inflammation. Moreover, ABH acutely reversed AHR after the early and late asthmatic reaction.Supporting evidence for this mechanism and thus for a role of arginase in the pathophysiology of allergic asthma and, potentially, other allergic disorders like allergic rhinitis was found in a guinea pig model of allergic asthma. Using this model, we discovered that inhalation of the potent specific arginase inhibitor 2, we demonstrated that arginase inhibition reduces guinea pig airway responsiveness in vitro by increasing NO production ; Refs. ARG1 and ARG2 polymorphisms are associated with asthma, asthma severity , and reduced responsiveness to \u03b22\u2010agonists and glucocorticosteroids.There is growing evidence for an important role of arginase in patients with asthma. Arginase 1 and arginase 2 expression and/or arginase activity are enhanced in asthmatic airways and in serum, and there is an association between arginase expression in bronchial brushings, serum arginase activity, plasma Studies in animal models and in asthmatic patients indicate an important role for both arginase 1 and arginase 2 in the pathophysiology of, particularly severe, asthma and allergic rhinitis. Therefore, arginase inhibitors, having an unique anti\u2010allergic, bronchoprotective, anti\u2010inflammatory, and anti\u2010remodeling profile, may be effective in the treatment of these diseases, possibly guided by the arginine metabolome in blood. Potential drugs are presently under development, some in clinical trials. As no subtype\u2010selective arginase inhibitors are presently available, development of such selective inhibitors to address potential, as yet unknown, differential roles of arginases 1 and 2 may further benefit patients suffering from these diseases.Dr. Meurs reports grants from Lung Foundation Netherlands, grants from N.V. Organon, Oss, The Netherlands, grants from Schering\u2010Plough Research Institute, Oss, The Netherlands, grants from Merck Sharpe and Dohme, Oss, The Netherlands, during the conduct of the study; grants from Netherlands Organisation for Scientific Research (NWO), grants from Carmolex Inc., Pittsburgh, PA, USA, outside the submitted work; In addition, Dr. Meurs has a patent Use of arginase inhibitors in the treatment of asthma and allergic rhinitis licensed to Carmolex Inc., Pittsburgh, PA, USA. Dr. Zaagsma reports grants from Lung Foundation Netherlands, grants from N.V. Organon, Oss, The Netherlands, grants from Schering\u2010Plough Research Institute, Oss, The Netherlands, grants from Merck Sharpe and Dohme, Oss, The Netherlands, during the conduct of the study; In addition, Dr. Zaagsma has a patent Use of arginase inhibitors in the treatment of asthma and allergic rhinitis licensed to Carmolex Inc., Pittsburgh, PA, USA. Dr. Maarsingh reports grants from N.V. Organon, Oss, The Netherlands, grants from Schering\u2010Plough Research Institute, Oss, The Netherlands, personal fees from Schering\u2010Plough, Kenilworth, NJ, USA, grants from Merck Sharpe and Dohme, Oss, The Netherlands, during the conduct of the study; In addition, Dr. Maarsingh has a patent Use of arginase inhibitors in the treatment of asthma and allergic rhinitis licensed to Carmolex Inc., Pittsburgh, PA, USA. At the time of this work Dr. van Duin was an employee of Organon/Schering Plough/Merck MSD and involved in the scientific collaboration with the corresponding author, Dr. Meurs. In addition, Dr. van Duin has a patent Use of arginase inhibitors in the treatment of asthma and allergic rhinitis licensed to Carmolex Inc., Pittsburgh, PA, USA."} +{"text": "The authors of the paper \u201cEpidemiology of Surgical Site Infections With Staphylococcus aureus in Europe: Protocol for a Retrospective, Multicenter Study\u201d :e63) made a mistake in the final stage of proofreading. In the affiliations list, Dr Liss\u2019s affiliation was incorrectly listed as \u201cDepartment I of Internal Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany\u201d. Instead, his affiliation should read \u201cDepartment I of Internal Medicine, Helios University Hospital Wuppertal, Wuppertal, Germany\u201d.The correction will appear in the online version of the paper on the JMIR website on January 7, 2019, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article also has been resubmitted to those repositories."} +{"text": "This Editor-in-Chief felt satisfied when he browsed the last volume of the European Journal of General Practice (EJGP). In 2018, we published 39 articles, including as many as 25 reports of original research. In addition to five articles with multinational authors, authors came from various countries across Europe, including Spain, France, Ireland, the UK, Belgium, the Netherlands, Latvia, Estonia, Germany, Poland, Switzerland, Hungary, Slovenia, Croatia, Serbia, and Turkey. The topics were as varied as a GP\u2019s working day, reflecting many aspects of family medicine and primary care. Many papers were on clinical topics like cardiovascular diseases, mental health, gastrointestinal diseases, infections, or Parkinson\u2019s disease. Furthermore, interdisciplinary collaboration , palliative care and end-of-life medicine, quality and safety issues, including polypharmacy were important overarching themes. Healthcare reform was another relevant topic. We also published several papers on medical education. Our four-paper series on qualitative research methodology published in 2017 and 2018 apparently met a need: over 20\u00a0000 views altogether and 21 citations thus far [Of all these publications, like last year, the EJGP editors each picked three articles they found most valuable. The highest-ranking paper, mentioned by three editors, was the original research article by Katarina Vu\u010di\u0107evi\u0107 and her colleagues from Serbia . The papAs of now, we re-introduce the \u2018four-issues-in-one-volume\u2019 format. That way, we try to offer the visitors of the EJGP website a clear overview of our publications. In 2019, we hope to publish the first parts of a series on eHealth . If you https://www.nhg.org/national-general-practice-research-agenda.I want to highlight one publication in this first issue of Volume 25. I know an Editor-in-Chief should be reluctant in promoting articles written by colleagues from his home country. However, I should like to make an exception for the article on the Dutch research agenda for general practice . The papFinally, I wish you all have a good start in 2019 and I hope it will become a successful year with a lot to read, think, and write about.Department of Family Medicine,Care and Public Health Research Institute (CAPHRI),Maastricht University, Maastricht, The Netherlands,ejgp-jstoffers@maastrichtuniversity.nl.Jelle Stoffers, Editor-in-Chief, the European Journal of General Practice,"} +{"text": "The data on the specifics of synthesis of elemental silver nanoparticles (Ag-NP) having various geometric shapes , obtained by using various biological methods, and their use in biology and medicine have been systematized and generalized. The review covers mainly publications published in the current 21st century. Bibliography: 262 references. N\u00e4geli ), as well as organic . The process of reducing Ag(I) compounds to elemental silver according to the Ag(I)\u2192Ag scheme can occur in a variety of reaction media; at the same time, specific chemical reagents (most often polyvinylpyrrolidone) are used to stabilize the resulting nanoparticles (to prevent their aggregation). The formation of Ag-NP, according to data et al) immobilized in a gelatin mass acts as a silver-containing precursor. The reducing agent is an organic or inorganic substance with strongly pronounced electron-donor properties. One of the most suitable for this purpose is tin dichloride SnCl2, which was used to obtain gelatin-immobilized Ag-NP in , but Ag(I) complexes with the inorganic and organic compounds named above, were actually reduced. The size of the pseudospherical Ag-NP obtained in this variant of biosynthesis is in the range from 10 to 40 nm; this was first experimentally established in [The literature contains a number of data showing the possibility of using for the synthesis of Ag-NP various products of animal origin, in particular polypeptide high molecular weight compounds (proteins). Owing to the large size of their molecules, the molecular mass of which (M) is tens and hundreds of thousands of carbon units , their role in this process is reduced mainly to function (3), i.e. substrates that hinder the aggregation of already formed nanoparticles is not excluded); in that way, these nanoparticles are immobilized in masses of these substrates. An example of such a substrate is gelatin, which is the main component of various food jellies. As known ,193,194,Ag-NP in ,200,201.ished in . In thisished in , their aished in ,202,203.Gelatin is not the only polypeptide substrate that can be used for this purpose; so, the various albumins are known for the synthesis of Ag-NP ,205,206.3 precursor in solution of this biopolymer was studied by Apryatina et al. [max) is at 424 nm, at M = 127,000 c.u., at 412 nm, at M = 165,000 c.u., at 400 nm, at M = 240,000 c.u., at 383 nm. Herewith, Ag-NP formed in chitosan solutions with a higher molecular mass and having a size of 8 nm, exhibit much more pronounced bactericidal activity than Ag-NP with a size of 12 nm [Another suitable substrate for the synthesis of Ag-NP can be a natural biopolymer chitin and chitosan derived from it. Chitosan is characterized by so-called mucoadhesive properties (ability to adhere to various mucous membranes) , which sa et al. ,213. It a et al. ,213 wereof 12 nm ,213. In of 12 nm Uryupina60Co isotope contributed to the restoration of the AgNO3 precursor. As a result of the studies, new radiation-induced bactericidal metal-polymer nanosystems containing the above biopolymer and elemental silver nanoparticles, were created. Besides, by varying the dose of \u03b3-radiation, as well as the degree of filling of the biopolymer macromolecules with Ag+ ions, the authors of works [In ,218,219,of works ,216 weremax in the range of 410\u2013425 nm were received. However, according to the authors of this article, systematic research in this direction has not yet been undertaken.Thus, in principle, other high-molecular compounds belonging to the number of polysaccharides, for example, agar-agar, carrageenan and guar, can be used as substrates for the production of silver nanoparticles. In pseudo-s2 matrix exhibits catalytic properties in redox reactions involving benzene, carbon monoxide, some dyes, and, possibly, many other chemical compounds. In particular, benzene under these conditions is almost completely oxidized to phenol even when the Ag-NP content in the matrix is about 1 mass. %. Reactions between sodium borohydride and dyes such as methylene blue and eosin, in the presence of Ag-NP in the reaction system, proceed at a very high rate, whereas in their absence such reactions practically do not take place. Besides, the SiO2 substrate actually serves only to prevent the aggregation of Ag-NP in a colloidal solution [Currently, elemental silver nanoparticles obtained by various methods are used in a very diverse fields of science and technology. Thus, an important area of application of Ag-NP is catalysis, which can be implemented in two versions: with the influence on the reaction system of electromagnetic radiation and without it. For example, in ,222 it wsolution ,227,228.solution , as a bisolution , in biocsolution , for prosolution and for solution . A layersolution .The foregoing, however, relates mainly to those Ag-NP that were produced by chemical and physicochemical methods. And although Ag-NP obtained using \u201cgreen synthesis\u201d could also find their application in the above areas of science and technology, nevertheless, their modern practical application is related to the field of their production. As in this case biosynthesis of Ag-NP, as a rule, was carried out in laboratories of biological and/or biochemical section with participation of experts in the field of biochemistry and biotechnology; attention of researchers was focused on the application of Ag-NP in biology, first of all in medicine and pharmacology.Staphylococcus aureus, Streptococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa and Escherichia coli: from bacteriostatic to bactericidal (ability to destroy microbes) [Bacillus [Staphylococcus [Pseudomonas [Klebsiella [Escherichia [Salmonella [Enterococcus [Serratia [Bacillus [Staphylococcus [Pseudomonas [Klebsiella [Escherichia [Salmonella [Enterococcus [Streptococcus [Currently, significant factual material related to bioapplications of Ag-NP already exists ,237,238.Bacillus ,103,106,lococcus , Pseudomudomonas ,100,103,ebsiella ,100,106,herichia , Salmonelmonella ,77, Enterococcus and SerrSerratia , was notBacillus ,162,186,lococcus ,186, Pseudomonas ,146,155,ebsiella , Escheriherichia ,186, Sallmonella ,186, Entrococcus and Stretococcus was obsetococcus . Meanwhitococcus . In quantococcus the disctococcus ,126,139 An important fact is that clearly expressed anticancer activity of silver nanoparticles was identified ,156,162.Staphylococcus and Escherichia [Ag-NP seems to be characterized by a highly synergistic bactericidal action in combination with such well-known antibiotics as penicillin, ampicillin, erythromycin, clindamycin and vancomycin; such a phenomenon has been observed, for example, against bacteria of the genus herichia . It shouherichia ,247. Anopheles [Plasmodium falciparum [Aedes and Culex [Another possibility for the application Ag-NP is their use as part of larvicidal compositions. In particular, it was proposed to use biosynthesized Ag-NP against malaria mosquitoes of the genus nopheles ,252,253,lciparum , and mosnd Culex . . Finally, it is very important to improve existing methods and develop new methods of isolating nanoparticles from the parent systems in which they were formed ."} diff --git a/PMC_clustering_213.jsonl b/PMC_clustering_213.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..350345d2e681d8f8cc986a5250695c05d852df93 --- /dev/null +++ b/PMC_clustering_213.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:f28282214bd518cee8b008b3fae034037365726ce3b40cd8c3369707f7ec67aa +size 71434901 diff --git a/PMC_clustering_214.jsonl b/PMC_clustering_214.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..347c83ac6efead007d6e9f80acbb28ee27c802c1 --- /dev/null +++ b/PMC_clustering_214.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:ab0d7dbeec5b0455b55b2253a480e18d57f79fe0926869af3e1fef7edd2d62ab +size 52956579 diff --git a/PMC_clustering_215.jsonl b/PMC_clustering_215.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..55ac424fc6756ee75c817634f24116a71956b05f --- /dev/null +++ b/PMC_clustering_215.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:979046857497872b3cd5f1fa9565193f67bf2d06f0e1020c05f94a3c5bb47d7a +size 34272538 diff --git a/PMC_clustering_216.jsonl b/PMC_clustering_216.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..85e71ffff2eeb1f7b78e120752267182076b2105 --- /dev/null +++ b/PMC_clustering_216.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:1d985b159a74034e47751a50bd18f62155db427b533b033fae901c6c76c42b9a +size 44595038 diff --git a/PMC_clustering_217.jsonl b/PMC_clustering_217.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..42415d6a3a57a40237f74ceb8dbef5394ea3b46b --- /dev/null +++ b/PMC_clustering_217.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:508fb6f6af3bc5546585b493fe3e911d8c74998f16d010b0b5a5884f2c70cc85 +size 11141423 diff --git a/PMC_clustering_218.jsonl b/PMC_clustering_218.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..336c161e4a8674aa9a42279720a6e290c17acd2b --- /dev/null +++ b/PMC_clustering_218.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:c4bef901fed1d60a9511ff4f7f66638aabfc42d605da34c044ab8e3f473b25bb +size 47704326 diff --git a/PMC_clustering_219.jsonl b/PMC_clustering_219.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..afc23a598fd158c6386e1d22239ee7a1496ed1ca --- /dev/null +++ b/PMC_clustering_219.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:3b98373c58f25b54399bb2f3b224d11d48ff54fcafadecccc979874fbc9a9680 +size 20124322 diff --git a/PMC_clustering_220.jsonl b/PMC_clustering_220.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..a5ea0a45b13a9f4fd0ca3542f517324fd75d31dc --- /dev/null +++ b/PMC_clustering_220.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:16dab93dfaab128f108c49bed9805418921c4973801db2e9e98832feb779e766 +size 91082107 diff --git a/PMC_clustering_221.jsonl b/PMC_clustering_221.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..e9572dbd5df2d41b6b4d3a6bd25422b8eba53a1e --- /dev/null +++ b/PMC_clustering_221.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:250b834044e14b8d126e22beaec016483f11e4b0216d3bf16c552c2b11775ba3 +size 140713127 diff --git a/PMC_clustering_222.jsonl b/PMC_clustering_222.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..16f1d1013690a484e6455e409a671aace9939142 --- /dev/null +++ b/PMC_clustering_222.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:bb71392b4ce255fdcb06603e405f09e271d56bcb28a5ffc9f7420d2e2540fca1 +size 11956171 diff --git a/PMC_clustering_223.jsonl b/PMC_clustering_223.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..033e3257e7527669e480ed353afceb1dcb2a7996 --- /dev/null +++ b/PMC_clustering_223.jsonl @@ -0,0 +1,319 @@ +{"text": "In The original images underlying the updated PLOS ONE\u2019s Editorial Board confirmed that the revised version of A member of The authors apologize for the error in the published article.S1 File(PPT)Click here for additional data file.S2 File(ZIP)Click here for additional data file.S3 File(ZIP)Click here for additional data file.S4 File(ZIP)Click here for additional data file.S5 File(ZIP)Click here for additional data file.S6 File(XLSX)Click here for additional data file."} +{"text": "The raw data underlying the results of this paper are missing from the list of Supporting Information. The authors have provided the data as Supporting Information file S1 DataThis file includes supplementary data.(XLSX)Click here for additional data file."} +{"text": "This report describes the 2020 Competition on Software Testing (Test-Comp), the 2"} +{"text": "A grant number from the funder JSPS KAKENHI is missing from the Funding statement. The missing grant number is: 16H06279 (PAGS) (TT). The publisher apologizes for the error."} +{"text": "Attitudinal Acceptance of Intimate Partner Violence Among Adolescents and Young Adults in Nigeria and Tanzania: An Exploration Into Target Reference Groups Order and Affiliation of Authorship. J Adolesc Health 2020;66:S3\u2013S8. The title is incorrect. The correct title is, \u201cAttitudinal Acceptance of Intimate Partner Violence Among Adolescents and Young Adults in Nigeria and Tanzania: An Exploration Into Target Reference Groups.\u201d"} +{"text": "The following information is missing from the Funding statement: This study was also supported by the Engineering and Physical Sciences Research Council (grants GR/R99393/01 and EP/C015452/1) to GK."} +{"text": "There is an error in Please see the Supporting Information files below for the underlying blots for The authors indicate that underlying images for other figures are available upon request.S1 File(ZIP)Click here for additional data file.S2 File(ZIP)Click here for additional data file."} +{"text": "In S1 Appendixv.Appendix indicating calculation of the new metric (DOCX)Click here for additional data file."} +{"text": "There are errors in the Funding statement. The publisher apologizes for the errors. The correct Funding statement is as follows: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government under Grant NRF-2019R1A4A1029769 and Grant NRF-2019R1I1A3A01058959."} +{"text": "The following information is missing from the Funding statement: This project has received funding from an EPSRC Impact Acceleration Grant (Grant number: EP/R511717/1)."} +{"text": "The sample in Additionally, the \u00d720 magnification image for The primary data underlying the rest of the results reported in this article are no longer available.S1 File(ZIP)Click here for additional data file."} +{"text": "The following information is missing from the Funding statement: This study has been funded by Instituto de Salud Carlos III through the project \"PI16/00748\" awarded to MI."} +{"text": "Scientific Reports 10.1038/s41598-023-40348-6, published online 21 August 2023Correction to: The Acknowledgements section in the original version of this Article was incomplete.\u201cThis paper is supported by Zhejiang Provincial Philosophy and Social Sciences Planning Project and Hangzhou Philosophy and Social Sciences Planning Project [grant number Z23JC066].\u201dnow reads:\u201cThis paper is supported by Zhejiang Provincial Philosophy and Social Sciences Planning Project, National Natural Science Foundation of China [grant number 72304246] and Hangzhou Philosophy and Social Sciences Planning Project [grant number Z23JC066].\u201dThe original Article has been corrected."} +{"text": "There are errors in the Funding section. The correct Funding statement is: The study was funded by Kuwait University Research Sector\u2019s grants RM01/13 and SRUL02/13."} +{"text": "Correction to: Journal of Epidemiology and Global Health (2023) 10.1007/s44197-023-00097-1In the original version of this article, the middle name and ORCiD of Ramy Mohamed Ghazy were missing and the sentence \u2018The figures were built using Microsoft Office 2016 and ggplot2 package built under R version 4.2.\u2019 should have read \u2018The figures were built using Microsoft Office 2016.\u2019The original article has been corrected."} +{"text": "There is an error in The original data underlying the Fig 2A results are provided in S1 File(XLS)Click here for additional data file."} +{"text": "Authors declare no conflict of interests for this article.I read with great interest the paper by Sinha et al. about Takotsubo syndrome (TS) in subjects undergoing catheter ablation for atrial fibrillation (AF) based on multicenter retrospective database.I have two comments and questions for the author: (1) Have you taken into consideration coronary spastic angina (CSA)? It is well known that CSA can be caused by direct thermal damage resulting from radiofrequency (RF) energy or an autonomic nervous system imbalance."} +{"text": "The Acknowledgment should becorrected to include the following: Sevban Do\u011fan Ekici sincerelyacknowledges the Turkish Ministry of National Education for theirsponsorship of her PhD studies. Joana do Mar Machado would like toacknowledge funding from the EPSRC Centre for Doctoral Training inSmart Medical Imaging (EP/S022104/1)."} +{"text": "S1 FileContains descriptions of various methods used in the study.(DOCX)Click here for additional data file."} +{"text": "Scientific Reports 10.1038/s41598-022-13624-0, published online 09 June 2022Correction to: The original version of this Article contained an error in the Acknowledgments section.\"This work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C2007397 and 2017M3D9A1073784), the Ministry of Education (2018R1A6A1A03024940) through Basic Science Research Program and the Korea Ministry of Environment (MOE) (2020002960004). We are also thankful for the financial support by a grant of the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number HI17C1238030021).\"now reads:\"This work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C2007397 and 2017M3D9A1073784), the Ministry of Education (2018R1A6A1A03024940) through Basic Science Research Program and the Korea Ministry of Environment (MOE) (2020002960004). We are also thankful for the financial support by a grant of the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number HI17C1238).\"The original Article has been corrected."} +{"text": "In the following article,The correct Figure 3 is shown below:The Supplementary Figure 2 has been corrected online.The authors apologize for the errors."} +{"text": "There are errors in the Funding section. The correct Funding statement is: This study was supported by four different funds: 1) Community Service Fund (83CT), The Hong Kong Polytechnic University; 2) Chinese Mainland Affairs Office Fund, The Hong Kong Polytechnic University; 3) Lions Clubs International MD300 Taiwan Eye Care Network Committee; and 4) InnoHK, HKSAR Government."} +{"text": "This Correction addresses errors in Figs Specifically, the incorrect underlying data were used in In The corrected The authors apologize for any inconvenience and confusion these errors may have caused.S1 File(XLSX)Click here for additional data file.S2 File(XLSX)Click here for additional data file."} +{"text": "Scientific Reports 10.1038/s41598-023-40954-4, published online 23 August 2023Correction to: The original version of this Article contained an error in the Funding section.\u201cThis paper is supported by the National Social Science Foundation of China Project Number: 21JBY179.\u201dnow reads:\u201cThis paper is supported by the National Social Science Foundation of China Project Number: 21BJY179.\u201dThe original Article has been corrected."} +{"text": "The ponceau loading control panels in The authors provide an updated version of The raw data underlying The authors apologize for the error in the published article.S1 File(PPTX)Click here for additional data file.S2 File(XLSX)Click here for additional data file."} +{"text": "The second author\u2019s name is spelled incorrectly. The correct name is: Eun A. Park.The following information is missing from the Funding statement: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government [grant number 2021R1F1A1045993]"} +{"text": "BMC Medical Genomics in the supplement containing selected articles from the IEEE International Conference on Bioinformatics and Biomedicine 2012 (IEEE BIBM 2012) [Our original article was published in"} +{"text": "To the Editor: I read with great interest the article regarding lymphocytic choriomeningitis virus (LCMV) meningitis in a New York City resident ("} +{"text": "There were errors in the typesetting of Tables in the article. Correct versions of the Tables are available below.Table 1: Table 2: Table 3: Table 4: Table 5:"} +{"text": "A funding organization was incorrectly omitted from the Funding Statement. The following sentence should be included with the Funding Statement: \"Co-author Phillip Olsen was supported partially by the Research Experiences for Undergraduates (REU) Program of the National Science Foundation.\"In addition, the following sentence should be read with the Acknowledgments: \"Authors would like to acknowledge Mutant Mouse Regional Resource Center U42OD010918 for providing mouse strain 011981-MU [Nagy ES cell line R1 with EGFP (B5)].\""} +{"text": "Retrovirology for publishing these erroneous data.The authors would like to retract the article \"The cellular source for APOBEC3G's incorporation into HIV-1\" (cited a"} +{"text": "The following information is missing from the Funding section: This study was supported by NIH grants R01CA118708 and R01CA166825."} +{"text": "The Supporting Information files were erroneously supplied as LaTeX files. Please see Appendix S1 and Appendix S2 at the following links:Click here for additional data file.Click here for additional data file."} +{"text": "Sensors in 2011 [The coefficient of the expression of Equation (6) was not properly written. Equation (6) should be corrected as"} +{"text": "There is an error in the key for Figure 2. The correct key for Figure 2 is:black dots: iso1green dots: iso10blue dots: ctrred dots: ate"} +{"text": "There is an error in Text S1. The correct file can be found here: Click here for additional data file."} +{"text": "The island outline in Figure 1 is inaccurate. The following link contains the corrected Figure 1 file: ."} +{"text": "The authors would like to add the following grant to their funding information: \"Faculty of Engineering research grant (2010), Burapha University Thailand (Grant #33/2553).\""} +{"text": "In Supplementary Table 1, the last line of the control primer sequence should read GAPDH GGGAGCCAAAAGGGTCATCATC TGGCATGGACTGTGGTCATGAG instead of GAPDH GGGAGCCAAAAGGGTCTCATC TGGCATGGACTGTGGCCGAG. Please find the corrected Supplementary Table 1 here: Click here for additional data file."} +{"text": "A revised version of Table S1 with additional information can be viewed here: Click here for additional data file.[^]"} +{"text": "The graphs are missing from Supplementary Figures S3 and S5. Please see the correct version of the figures here:Figure S3: Click here for additional data file.Figure S5: Click here for additional data file."} +{"text": "The following information was missing from the funding section: Austrian Science Fund (P21667-B09)."} +{"text": "The authors wish to add the following to their Funding section: \"This initiative is funded by the CTSI (grant by number 1 UL1 RR029893).\""} +{"text": "A second grant given by the National Cancer Institute was incorrectly omitted from the Funding statement. The number of the second grant is: 1RO1 CA109478."} +{"text": "The Appendix S1 Maternal Severity Index Calculator is currently unavailable for reader use. The accessible file can be found here: Click here for additional data file."} +{"text": "There are multiple errors in the titles for Figure 3 and 4. The correct titles for the figures are:In figure 3D: the tile should be: Luminal A In figure 4A: the title should be: All patients In figure 4B: the title should be HER2 In figure 4C: the title should be Basal In figure 4D: the title should be Luminal-A In figure 4E: the title should be Luminal-B"} +{"text": "Figure S1 of the Supporting Information section is missing several parts. Please see the corrected Figure S1 here: Click here for additional data file."} +{"text": "The number of the grant from Kaohsiung Medical University Hospital is incorrect. The correct grant number is: KMUH100-0M08."} +{"text": "A funding organization and funding program were incorrectly omitted from the Funding Statement. The Funding Statement should read: \"This work was supported by NIH/NINDS 5P50NS037409 (XOB and NS) and by the Parkinson's and Movement Disorder's Foundation (PMDF 2011).\""} +{"text": "The Supporting Information files, Data S1 and Data S2, are corrupt. The correct files can be viewed here:Click here for additional data file.(Data S1)Click here for additional data file.(Data S2)"} +{"text": "Two additional grants from the National Eye Institute were incorrectly omitted from the Funding Statement. The numbers of the two grants are: R24EY022012 and R01EY017549."} +{"text": "The following funding source was omitted from the published article: The Multicenter AIDS Cohort Study is funded by the National Institutes of Health grant NIH 2 U01 AI035039-22."} +{"text": "The files for Figures S6 and S7 are incorrect. Please view the correct Figure S6 here: Click here for additional data file.and view the correct Figure S7 here: Click here for additional data file."} +{"text": "The authors with to add the following funding source to their financial disclosure information: The work was partly supported by Scott & White RGP Award (R8000 R3536) to SG."} +{"text": "A file was erroneously omitted from the list of Supporting Information. The full derivation of Equation 1 can be viewed here: Click here for additional data file."} +{"text": "The formatting of Table 5 contained an error. The correct version of Table 5 can be seen here: [^]"} +{"text": "There is an error in Figure S3. The correct mutations for Sample ISBLAC3803 are S571L TCG>TTG and S614* TCA>TGA. Please view the corrected Figure S3 here: Click here for additional data file."} +{"text": "The following information was missing from the Funding section: This work was also funded by Taipei Medical University (TMU100-AE3-Y15)."} +{"text": "An error in the file extension was introduced during the production process for Figure S1. Figure S1 can be viewed here: Click here for additional data file."} +{"text": "There were errors in Supporting Tables S6 and S7.Please see the corrected Table S6 here: Click here for additional data file.Please see the corrected Table S7 here: Click here for additional data file."} +{"text": "In Reply: The Croatian Medical Journal strictly follows the rule that manuscripts based on unregistered clinical trials are immediately rejected (rejected -3."} +{"text": "The Supporting Information Table 1 was incorrectly uploaded. Please view the correct Supporting Information Table 1 file here: Click here for additional data file."} +{"text": "A funding source was omitted from the published funding statement. The authors would like to add: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement n\u00b0 259679 (IDEAL)."} +{"text": "Errors occurred in the preparation of Figure S3. Please see the corrected Figure S3 here: Click here for additional data file."} +{"text": "Figure S6 is incorrect. Please see the correct version of Figure S6 here: Click here for additional data file."} +{"text": "Two additional grants from the NIH to the fifth author (ELB) were incorrectly omitted from the Funding Statement. The numbers of the two grants are: NIMH R01 MH096093 and NINDS R01 NS062184."} +{"text": "A funding organization for the seventh and eighth authors was incorrectly omitted from the Funding Statement. The Funding Statement should read: The work is supported by R33 grant from NCI (4R33CA126209) through Clinical Proteomic Technologies for Cancer(CPTC)to XG and XZ."} +{"text": "The following information is missing from the funding statement: LKJ was funded in part by the ARRA supplement grant to the CoBRE \u201cCenter for the Analysis of Cellular Mechanisms and Systems Biology\u201d (3P20RR024237-02S1). Support for the NMR Facility at MSU was provided by the NIH Shared Instrumentation Grant program (grants # 1S10RR13878 and 1S10RR026659)."} +{"text": "Video S1 and Video S3 have been switched in the Supporting Information. Please view the correct videos and their description below.Video S1First day culture of normal newborn ovary. A square indicates somatic cell invasion of oocyte cyst.(MP4)Click here for additional data file.Video S3First day culture of Figla null newborn ovary.(MP4)Click here for additional data file."} +{"text": "The Supporting Information files in the paper do not appear properly. The correct files can be found here:Figure S1: Click here for additional data file.Figure S2: Click here for additional data file."} +{"text": "The column headings in Dataset S3 are incorrect due to a formatting error. The Column headings in Columns K-P were originally presented in an incorrect order. Please view the correct Dataset S3 here: Click here for additional data file."} +{"text": "Table S4 does not correctly download from the article. Please view the correct file for Table S4 here: Click here for additional data file."} +{"text": "The supporting information file Figure S1 is the wrong file. Please view the correct Figure S1 file here: Click here for additional data file."} +{"text": "The correct name of the third author is: Kevin ThurleyThe correct version of Figure 5 available here:"} +{"text": "This article is missing the Supporting Information File \"Text S1\". Please use the following link to access Text S1: Click here for additional data file."} +{"text": "A figure file was erroneously omitted from the list of Supporting Information. The publisher apologizes for the error. The figure's description is \"Detection of a splenic IL-2 transcript after 2 h of TCR-2 stimulation,\" and it can be viewed here: Click here for additional data file."} +{"text": "The file Text S1 was published in an incorrect format. Please view the correct Text S1 file here: Click here for additional data file."} +{"text": "The three p-values in the far right column of Table 2 should align with the categories of Long term (%), Day hospital (%), and Out-patient visit (%). Please see the corrected Table 2 here:"} +{"text": "The most recent version of Table 4 was not included in the final manuscript. Please see the correct Table 4 here: The current Table S1 mistakenly contains all the markers of the RosBREED SNP array. Please find the corrected Table S1 which only includes markers used in the manuscript here: Click here for additional data file.The wrong version of Figure S2 was included in the final article. Please see the correct Figure S2 here: Click here for additional data file."} +{"text": "There was an error in the text \"B(i)B(i)\" in the third paragraph under the \"Sequence Centrality\" heading. The correct text is \"B(i)\"."} +{"text": "The Competing Interests statement is incorrect. The correct Competing Interests statement is: The University Medical Centre Hamburg-Eppendorf has filed patent US8101352B2 \u201cDetection of ESR1 Amplification in Breast Cancer\u201d and accordant patent applications in EU and CA for certain technology described in this paper."} +{"text": "Please see Figure 1 with the correct names here: The caption names for G"} +{"text": "There were errors in Table S1. The correct version of the file is available here: Click here for additional data file."} +{"text": "Scientific Reports6: Article number: 23351;10.1038/srep23351 published online: 03302016; updated: 04222016This Article contains typographical errors in a grant number in the Acknowledgements section.\u201cThis work was supported by grants National Natural Science Foundation of China ,\u201dshould read:\u201cThis work was supported by grants National Natural Science Foundation of China ,\u201d"} +{"text": "There is an error in the Supporting Information File S1Implementation of the SI algorithm in Matlab. The software includes a manual and user friendly interface Song_gui.(ZIP)Click here for additional data file."} +{"text": "In the Funding section, the grant number NNJ10ZSA001N from the funder National Aeronautic and Space Administration has been updated by the funder. The updated grant number is: NNX11AD22G."} +{"text": "The following information is missing from the Funding section: This study was supported by the S\u00e3o Paulo Research Foundation (FAPESP) grant: 2015/15699-5."} +{"text": "Additionally, there is a sentence missing from the caption for S1 Blot(PPTX)Click here for additional data file."} +{"text": "There are errors in the equations of file S1 Text(PDF)Click here for additional data file."} +{"text": "The authors have prepared a revised manuscript to address comments left by readers regarding the species examined in this article as well as the classification of pestiviruses. Please view a revised manuscript provided as Supporting Information , a revisS1 File(PDF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file."} +{"text": "There is an error in the Supporting Information where the incorrect database is linked. Please view the correct S1 Text(XLSX)Click here for additional data file."} +{"text": "A 27 year old patient presented with primary infertility of 3 years' duration and also a history of myomectomy (5 years ago) was referred to our infertility clinic for investigation of infertility. The latest Hysterosalpingography (HSG) revealed an obstructed left fallopian tube with apparently a unicornuate uterus with luminal contour irregularity and normal left fallopian tube . Signifi"} +{"text": "The legends for S1 FilePDF version of the questionnaire made of screenshots from the online survey tool.(PDF)Click here for additional data file.S2 FileA PDF file containing further screenshots from 3D PDF reports described in this article. This file also contains download links for complete 3D PDF reports.(PDF)Click here for additional data file."} +{"text": "The article has been correctedonline.In the article \u201cA Retrospective Study of the Impact of Intraoperative IntactParathyroid Hormone Monitoring During Total Parathyroidectomy for SecondaryHyperparathyroidism: STARD Study,"} +{"text": "The following information is missing from the Funding and Acknowledgments sections: This research was supported by a grant (NRF-2013R1A1A2058169) from the National Research Foundation."} +{"text": "S1 FileCharacteristics of the sample and individual responses to high-intensity interval exercise bout.(XLSX)Click here for additional data file."} +{"text": "After publication of this Research Article , we noteCorrected version of articleBMC Cancer14:503.(PDF 433 KB)Additional file 1:"} +{"text": "The following information is missing from the Funding section: This study was supported by grant EU-ERDF (PI12/00378) from the Instituto de Salud Carlos III."} +{"text": "There is an error in S1 TableThis table lists the genes included in the siRNA library alongside the gene accession number and the median Z scores from three replicate screens for each cell line.(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: Instituto de Salud Carlos III and Fondos Feder (PI12/00104) partially supported this research."} +{"text": "There are errors in the annotation column of S2 TableHT: genes were only found in the HT group; HC: genes were only found in the HC group; *: padj>0.05.(XLSX)Click here for additional data file."} +{"text": "The incorrect S1 File appears in the published paper. Please view the correct S1 TextThis file contains a list of the 36 questions included in the mSRS. Please view the correct S1 Text here.(DOCX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was funded by the Medical Research Council (grant number MR/J50032X/1)."} +{"text": "There is an error in Fig 2 of the published article. Panel (a) was replaced with a copy of Fig 1.The Supporting Information file S1 Equations contains the incorrect set of differential equations.Please see corrected S1 Equations(PDF)Click here for additional data file."} +{"text": "Due to a clerical error by the authors, S1 File(PPTX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: HR and BDL were funded by United States\u2019 Public Health Service Grant R01 AI089826."} +{"text": "The following information is missing from the Funding section: Funding was provided by NCI 1 R03CA162505-1 with an Administrative Supplement from the Office of Dietary Supplements."} +{"text": "The following information is missing from the Funding section: This work was funded by the Medical Research Council (grant number MR/J50032X/1)."} +{"text": "There is an error in the legend for Table S1Average binding energy and Rosetta energy obtained for each residue mutation of Vif complexed to EloBC-A3G N-CDA.(DOC)Click here for additional data file."} +{"text": "There are errors in the Supporting Information. In In Please view the corrected Datasets S1 Data(DOCX)Click here for additional data file.S2 Data(CSV)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was supported by National Institute of Health R01HD072848-01A1."} +{"text": "There are errors in the Funding section. The publisher apologizes for these errors. The correct funding information is as follows: This work is supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIP) GRANT numbers: 2015R1A5A001906 and 2013M3A9C4078158."} +{"text": "There is an error in the Supporting Information Analysis S1(DOCX)Click here for additional data file."} +{"text": "The authors would like to correct S1 Data and Images(ZIP)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: Support for this publication was obtained with Grant 2014/1898-7 from the Sao Paulo Research Foundation (FAPESP)."} +{"text": "The first concern was about Figure 2c ('middle right panel: The right 2 lanes look very similar') whilst the second was about Figure 3b ('PK-panel: A rectangle with a much lighter background than the rest of the blot appears to be visible in the first 4 lanes.').Concerns have been raised about two of the figures published in this article , who is satisfied with the authors' response to the concerns.Please find the original gels included below as supporting information files.S1 Gel(TIF)Click here for additional data file.S2 Gel(TIF)Click here for additional data file."} +{"text": "File S1 is an accidental duplicate of File S2. The correct File S1 can be viewed below.File S1Level assignments in the Lapakahi detailed study area for plotting with Google Earth.(ZIP)Click here for additional data file."} +{"text": "One line on each page of Figure S5Corrected FigurePDFClick here for additional data file."} +{"text": "The second group heading in column one of S2 Table(XLSX)Click here for additional data file."} +{"text": "The HIV-1 sequence data are missing from the published article. Please view these data as file S1 Data(DOCX)Click here for additional data file."} +{"text": "The authors would like to correct The authors have provided a corrected version of S1 File(PPT)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This study was supported by the Geophysical Fluid Dynamics Institute (GFDI) (Contribution Number 470). Both LG and CH were partially supported by GFDI."} +{"text": "Table S1 in the published article is missing three primers. Please view the corrected version of Table S1 here for the complete list of primers, with omissions highlighted in yellow.Table S1Primers used in this study, including specifications for the amplification PCR .(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This study was supported by a grant from the Deutsche Forschungsgemeinschaft (SCHE 307/7-1) to GSB. The publisher apologies for this error."} +{"text": "Please view the correct In There are a number of errors in tmlY, and the gene name at coordinate 79587..80669 should be tmuA. Please view the correct Table S1 here.In Table S1, the gene names at coordinates 78712..79242 and 79587..80669 are incorrectly switched. The gene name at coordinate 78712..79242 should be Table S1Predicted gene products of pTML1.(DOC)Click here for additional data file."} +{"text": "There are errors in the Supporting Information file S1 Text(DOC)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This study was supported by CNPq grant 485757/2007-9."} +{"text": "The following information is missing from the Funding section: This research is supported by UM Grant Challenge Grant GC003A-14HTM."} +{"text": "There is an error in There are formatting errors in the Supporting Information files Appendix S1Some properties of the proposed functional diversity measures.(PDF)Click here for additional data file.Appendix S2Decomposition of the proposed functional diversity measures.(PDF)Click here for additional data file.Appendix S3Four classes of functional similarity/differentiation measures.(PDF)Click here for additional data file.Appendix S4Functional beta diversity and functional diversity excess lead to the same classes of similarity and differentiation measures.(PDF)Click here for additional data file.Appendix S5Supplementary examples and comparisons.(PDF)Click here for additional data file."} +{"text": "S1 DataThe association of ICP with locus-specific Indigenous American ancestry was tested with logistic regression. S1 Data shows the admixture mapping results for all 109917 markers across the genome.(ZIP)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was also partially supported by the Worldwide Cancer Research grant (N\u00b014-0346 to S.T.)."} +{"text": "There are errors to the Accession and Code in Analyses columns of Table S1. Please view the correct Table S1 below.Table S1Sample Information including GenBank accession numbers for newly published sequences used in this study.(PDF)Click here for additional data file."} +{"text": "In The authors would like to correct Figs The authors confirm that these changes do not alter their findings. The authors have provided the underlying images for all figures in the original article as Supporting Information.S1 File(ZIP)Click here for additional data file.S2 File(ZIP)Click here for additional data file.S3 File(ZIP)Click here for additional data file."} +{"text": "There are a number of errors in S5 Table(XLSX)Click here for additional data file."} +{"text": "Scientific Reports6: Article number: 2642810.1038/srep26428; published online: 05262016; updated: 07072016This Article contains errors in the Acknowledgements section.\u201cThe authors acknowledge funding support from the National Health and Medical Council of Australia (1004926).\u201dshould read:\u201cThe authors acknowledge funding support from the National Health and Medical Research Council of Australia (1004926) and Diabetes Australia.\u201d"} +{"text": "Scientific Reports5: Article number: 1161710.1038/srep11617; published online: 07012015; updated: 06202016In this Article, there is an error in Figure 3 where the formation of the ATP molecule between the reaction steps 3PGA and 2 Pyruvate should be omitted. The correct Figure 3 appears below as"} +{"text": "The top panel of western blots in S1 Blots(ZIP)Click here for additional data file."} +{"text": "There are formatting errors in Table S1Proportions of Parkinson's Disease Patients Prescribed Anti-Parkinson Drugs According to Two Age Groups.(DOC)Click here for additional data file."} +{"text": "Table S2 contains track changes in both the XML and PDF versions of the article. Please see the corrected Table below.Table S2Annotation entry statistics for 1555 human transporter genes.(DOC)Click here for additional data file."} +{"text": "Scientific Reports6: Article number: 25035; 10.1038/srep25035 published online: 04282016; updated: 06102016The Acknowledgements section in this Article is incomplete.\u201cThanks very much for the contributions on statistical work by Dr Qian Zhou\u201d.should read:\u201cThanks very much for the contributions on statistical work by Dr Qian Zhou. This work was supported by grants from the National Natural Science Foundation of China (Grant 81370786)\u201d."} +{"text": "The original version of this article referredAdditional file 1:Plasmonic molecules via glass annealing in hydrogen: supplementary materials."} +{"text": "The following information is missing from the Funding section: BG is supported by NIH P30 AG10133."} +{"text": "There is an error in the layout of question 7 in S1 Reduced Model(PDF)Click here for additional data file."} +{"text": "The Supporting Information files S1 MOVIEResults from this data processed with MATtrack can be seen in Fig 6.(MOV)Click here for additional data file.S2 MOVIEResults from this data processed with MATtrack and AndorIQ2 can be seen in Fig 7.(MOV)Click here for additional data file.S1 FileInstallation and operation instructions for MATtrack.(PDF)Click here for additional data file.S2 File(ZIP)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: Caroline Brennan was supported by (UK) Medical Research Council grant G1000053."} +{"text": "The correct Data Availability Statement should read: Data are available from Dryad Digital Repository (doi:"} +{"text": "The following information is missing from the Funding section: This work was also supported by Czech Science Foundation no. P505/11/2387."} +{"text": "PLOS ONE editorial team would like to express our gratitude to all those individuals who participated in the peer review process of submissions to PLOS ONE over this past year. During 2015 PLOS ONE published over 28,000 research articles. This would not have been possible without the contribution of more than 76,000 reviewers from around the world and a wide range of disciplines.PLOS and the PLOS ONE reviewers are listed in PLOS ONE authors in the evaluation of their work. Your efforts are a key reason for PLOS ONE\u2019s success as an innovative and influential publication.The names of our 2015 S1 Reviewer List(PDF)Click here for additional data file.S2 Reviewer List(PDF)Click here for additional data file.S3 Reviewer List(PDF)Click here for additional data file.S4 Reviewer List(PDF)Click here for additional data file.S5 Reviewer List(PDF)Click here for additional data file."} +{"text": "The article has since been corrected online.In the article \u201cEvaluation of Safety and Efficacy of Salvage Therapy With Sunitinib, Docetaxel (Tyxane) and Cisplatinum Followed by Maintenance Vinorelbine for Unresectable/Metastatic Nonsmall Cell Lung Cancer Stage 1 of a Simon 2 Stage Clinical Trial\u201d,"} +{"text": "The following information is missing from the Funding section: this work is supported by the National Science & Technology Pillar Program (2014BAJ04B02)."} +{"text": "The following information is missing from the Funding section: This study was also supported by grant NIH P30 DK056341 from the Washington University Nutrition Obesity Research Center."} +{"text": "Scientific Reports 10.1038/s41598-023-29909-x, published online 27 February 2023Correction to: The Acknowledgments section in the original version of this Article was incomplete.\u201cThis research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1C1C2005307 and 2017R1A6A1A03015876).\u201dnow reads:\u201cThis research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1C1C2005307 and 2017R1A6A1A03015876). It was also supported by the grant of the Korea Health Industry Development Institute .\u201dThe original Article has been corrected."} +{"text": "DOI: 10.1039/D1RA04855D.Correction for \u2018An indenocarbazole-based host material for solution processable green phosphorescent organic light emitting diodes\u2019 by Eun Young Park The authors regret that an incorrect version of The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Journal of Healthcare Engineering has retracted the article titled \u201cClinical Study on the Relationship between the SNP rs8192675 (C/C) Site of SLC2A2 Gene and the Hypoglycemic Effect of Metformin in Type 2 Diabetes\u201d [Following an investigation conducted by the Hindawi Research Integrity team , signifiThe authors do not agree to the retraction."} +{"text": "The errors appear only in PDF versions downloaded on or before April 7, 2022."} +{"text": "The authors would like to make a correction in a recently published paper . There wOriginal Figure 1:We would like it to be corrected as shown below.New Figure 1:Original Figure 2:New Figure 2:Original Figure 4:New Figure 4:The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "The results of sensitivity analyses using the isometric log transformed activity variables were incorrect. The results have been corrected in In the fifth paragraph of the Results section, the third sentence is incorrect. The paragraph should read:Results of sensitivity analyses using \u201cother day\u201d imputed data were broadly consistent with the results of our main analyses using the complete days data . Results of sensitivity analyses excluding BMI and ill health as covariates were comparable to our main analyses (S4\u2013S6 Tables). Results using isometric log ratio transformed activity variables were largely consistent with our main analyses \u2013S12 FigsS10 Fig(PDF)Click here for additional data file.S11 Fig(PDF)Click here for additional data file.S12 Fig(PDF)Click here for additional data file."} +{"text": "The original version of this article unfortunately contained a mistake. The peptide sequence (R)ICSINSPGVRPFGAK(D) on pages 3 and 7 is incorrect. The correct sequence is: (R)GEKGEAGPPGAAGPPGAK(G). The authors state that this mistake in displaying the peptide sequence does not affect other results or interpretation of the data. The original article has been corrected."} +{"text": "S1 TextCriteria, thresholds, and levels used in model of impact and resource needs.(PDF)Click here for additional data file."} +{"text": "Since online publication of this article (1) The statistical graph of BrdU (+) cells number for C33A cells after LGALS1 overexpression in Figure (2) The flow cytometric image of Control-shRNA group for C33A cells in Figure (3) The statistical graph showing the relative level of Fascin protein for C33A cells in Figure The correction does not affect the original results and conclusions of this study. The authors apologize for any inconvenience or misunderstanding caused."} +{"text": "In the original article , there wThe Original Figure 1:The Correct Figure 1:"} +{"text": "The following information is missing from the Funding statement: This work was supported by NIH grant 1R01NS114007-01A1."} +{"text": "In the original publication of this article , the product OSOM Ultra Flu A&B Test was incorrectly referred to as OSOM Ultra Plus Flu A&B Test. This has been corrected in the version currently available online."} +{"text": "In our paper, the Western Blot bands #01 and #03 in Figure"} +{"text": "The following information is missing from the Funding statement: This article was supported by Gazi University Scientific Research Projects Unit with grant number 5959, code 64/2020-03."} +{"text": "There are errors in the Supporting Information. S1 TextRNA isolation using phase extraction and ETOH precipitation\u2014suitable for samples with high carbohydrate content.(DOCX)Click here for additional data file.S2 Text(PDF)Click here for additional data file."} +{"text": "Funding statement was erroneously omitted. The correct Funding statement appears below.In the published article, the \u201cThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2018R1D1A1B07050568).\u201dThe authors apologize for this error and state that this does not change the scientific conclusion of the article in any way. The original article has been updated."} +{"text": "An error was identified in the S1 Data(XLSX)Click here for additional data file."} +{"text": "The authors regret that some articles reporting probes for detecting human NAD(P)H:quinone oxidoreductase 1 were not cited in the original article. The missing references are listed below as 1\u20136Herein, we designed and synthesized a novel fluorescent probe 1 for detection of hNQO1 based on TCF-OH as a chromophore and quinone propionic acid (QPA) as a recognition group.The authors sincerely apologise for this oversight.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "DOI: 10.1039/D1RA01427G.Correction for \u2018Nano zero valent iron (nZVI) particles for the removal of heavy metals (Cd The correct reference is given below as reference 1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Funding/Support should have included grants R01AG038791 and U19AG063911 from the National Institutes of Health to Dr Boxer. This article has been corrected.1In the Original Investigation titled \u201cDiagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration,\u201d"} +{"text": "The following grant number is missing from the Funding statement: ES/P000681/1. The correct Funding statement is as follows: This study was carried out with PhD funding received by CDF from the Economic and Social Research Council (ESRC) under the grant reference numbers ES/R5009381/1 and ES/P000681/1."} +{"text": "The original version of this article unfortunIn recent research work, the mistake occurred on primer sequence of NR2B for RT-PCR shown in Table The corrected primer sequence of NR2B should be as followingsForward: GCTCATCGCCAAGGGTACATCReverse: TGCACTATTTCAAGTCACATGCCTAThe correct version of Table"} +{"text": "Pegasus species individuals in Plate B are incorrect. Please see the correct In Pegasus species individuals in The COI GenBank Accession Numbers for the S2 Table(XLSX)Click here for additional data file."} +{"text": "PLOS ONE\u2019s figure preparation guidelines, instead the lower bands should have been included in the published panel, and the text should have commented on the inconsistency.Following the publication of this article concernsThis Correction notice is issued to update the S1 File(BMP)Click here for additional data file.S2 File(TIF)Click here for additional data file.S3 File(BMP)Click here for additional data file.S4 File(TIF)Click here for additional data file."} +{"text": "The Funding/Support statement should have included the following sentence: \u201cMs Ricket was supported in part by BD2K T-32 Training Grant (T32 LM012204) from the National Institutes of Health.\u201d This addition does not affect the Role of the Funder/Sponsor information. This article has been corrected.1In the Original Investigation titled \u201cDevelopment of Electronic Health Record\u2013Based Prediction Models for 30-Day Readmission Risk Among Patients Hospitalized for Acute Myocardial Infarction,\u201d"} +{"text": "An error was made in preparing the Actin panel of The authors apologize for the S1 FileIndividual-level data for (XLSX)Click here for additional data file."} +{"text": "Advocate Aurora Health was incorrectly placed in Category 4 rather than Category 3 due to a typographical error. This has been fixed, and all other information in the Supplement remains correct.The Original Investigation titled \u201cFactors Associated With Overuse of Health Care Within US Health Systems: A Cross-sectional Analysis of Medicare Beneficiaries From 2016 to 2018,\u201d"} +{"text": "The following information is missing from the Funding statement: LD and EBP are supported by Medical Research Council (MRC) (MC/PC/19067). LL acknowledges funding from a QMUL\u2019s COVID Response Grant."} +{"text": "After this article was publThis article\u2019s Results section includes six statements that reference data not shown. The results underlying these statements are in The data underlying results reported in this article are available upon request from the first author.S1 File(ZIP)Click here for additional data file.S2 File(PPTX)Click here for additional data file.S3 File(ZIP)Click here for additional data file."} +{"text": "The Funding statement is incorrect. The correct Funding statement is as follows: HF was funded by a Medical Research Council Clinical Research Training Fellowship (grant reference number MR/T001585/1). The remaining authors received no specific funding for this work."} +{"text": "There are errors in the Funding statement. The correct Funding statement is as follows: This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (HI14C1851) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2018R1A2B6007648 and 2020R1I1A1A01072520)."} +{"text": "The following information is missing from the Funding statement: The publication of this article was supported by the Federal University of Par\u00e1 (UFPA) (PROPESP-PAPQ 01/2020\u2014QUALIFIED PUBLICATION SUPPORT PROGRAM)."} +{"text": "The following information is missing from the Funding statement: This work was supported by the National Research Foundation of Korea (NRF); the Korea government (MSIT) (No. NRF-2020R1C1C1007913)."} +{"text": "There are misleading errors in the mathematics deriving an algorithm in S2 TextMathematical process for deriving the PIPPET and PATIPPET filters from existing point process filtering equations.(PDF)Click here for additional data file."} +{"text": "The authors regret that:The EPSRC grant number currently stated in Funding Source section is `EP/K030957/1', which is incorrect. The correct funding source is `EP/N024818/1'.The authors would like to apologise for any inconvenience caused."} +{"text": "In Clark (2022)The updated Figure 2 is shown below:The online version has been updated to reflect this change."} +{"text": "Environ Health Perspect 113:1366\u20131372 (2005)], the authors noted errors in In the article by Rosenman et al. [3.The correct mean exposure levels for the DWA categories in"} +{"text": "Accession numbers for 8 assemblies included in this analysis are missing from These accession numbers are also missing from the Data Availability statement. The correct statement is: All complete genome assemblies are available from the NCBI Genbank database . All sequencing data is available from the NCBI Sequence Read Archive database .S2 Table(DOCX)Click here for additional data file."} +{"text": "One data point is inadvertently omitted from the upper left graph in Several data points were inadvertently omitted from the data set used for analysis . These dPlease see the complete, correct S1 Dataset(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: PB and MB were also funded by MRC grant MR/M02010X/1."} +{"text": "Scientific Reports6: Article number: 2775410.1038/srep27754; published online: 06132016; updated: 03232017The Acknowledgements section in this Article is incomplete.\u201cThis study was supported by grants from the Australian Research Council . The authors thank Petra C van den Bogert for help with data collection\u201d.should read:\u201cThis study was supported by grants from the Australian Research Council . The authors thank Petra C van den Bogert for help with data collection. This work was also supported by an International Research Staff Exchange Scheme (612681) of the EU 7th Framework Programme\u201d."} +{"text": "The following information is missing from the funding statement: PPAS was supported by an AXA Research Fellowship, British Ecological Society grant 4785/5824 and the National Socio-Environmental Synthesis Center (SESYNC)\u2014NSF award DBI-1052875.The \u03f5 labeling the key for Fig 1 should be replaced with the symbol r. The authors have provided a corrected Figure here."} +{"text": "There are two errors in Additionally, in S1 File(ZIP)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was supported by the Biotechnology and Biological Sciences Research Council (grant BB/J014508/1)."} +{"text": "Scientific Reports6: Article number: 2360910.1038/srep23609; published online: 03292016; updated: 10192016The original Supplementary Information published with this Article contained an error in the order of the Figures. Figures S9 and S10 were published as Figures S10 and S9 respectively. This error has now been corrected in the Supplementary Information that now accompanies the Article."} +{"text": "In In Supplementary Table A of S1 TablesSupplementary Table A: Patient Characteristics . Supplementary Table B: Patterns of Corticosteroid user characteristics among Veteran with and without corticosteroids for IBD only.(DOCX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: National Institute of Mental Health also provided funding under award number R01GM105045 ."} +{"text": "The figure legend for Fig 1 is incorrect. I5 in the figure legend is missing. The figure caption is also missing. Please see the complete and correct Additonally, the Supporting Information files S1 Fig(DOCX)Click here for additional data file.S2 Fig(DOCX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: Funding for this open access publication was provided by the FP7 Post-Grant Open Access Pilot."} +{"text": "The authors would like to correct The authors confirm that these changes do not alter their findings. The authors have provided raw, uncropped blots as Supporting Information.S1 File(TIF)Click here for additional data file.S2 File(TIF)Click here for additional data file."} +{"text": "An incorrect version of the Supporting Information file S1 Script appears with the paper. Please see the correct version here.S1 Script(ZIP)Click here for additional data file."} +{"text": "Additional file 2: Table S1 should indicate the list of differentially expressed WSD/Chow genes (instead of WSD/CR).The title for The correct title on the figure and within the article should therefore be:Additional file 2: Table S1. The list of differentially expressed WSD/CHOW genes identified in the present study.Additional file 2: Table S2 should indicate the list of differentially expressed CR/Chow genes (instead of CR/WSD).The title for The correct title on the figure and within the article should therefore be:Additional file 2: Table S2. The list of differentially expressed CR/CHOW genes identified in the present study.After the publication of this article the authThe original article has been corrected."} +{"text": "The correct version of Table S2 now appears online.The authors apologise to readers for this mistake."} +{"text": "The following information was missing from the Funding section: This study was supported by a Postdoctoral Award (#11POST5820019) from the American Heart Association (R.T.)."} +{"text": "S1 File. PRISMA 2009 Checklist.The caption for the PRISMA Checklist in the Supporting Information files is incorrect. The caption should read: S1 Fig(TIF)Click here for additional data file."} +{"text": "Scientific Reports5: Article number: 1409910.1038/srep14099; published online: 09152015; updated: 02062017The authors of Article made an error in preparation of the final version of Figure 2 and inadvertently used panel 2C as both panel 2Ab and panel 2C. A revised version of This correction does not affect the conclusions of the Article. The authors apologize for the error and any inconvenience caused by it."} +{"text": "Nature Communications8: Article number: 14357; DOI: 10.1038/ncomms14357 (2017); Published 02272017; Updated 04112017The original version of the Supplementary Information attached to this Article did not include Supplementary Note 1 The HTML has now been updated to include a corrected version of the Supplementary Information."} +{"text": "The reference for the origin of the strain WM210 is missing in S1 Table(DOCX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was supported by NIH grant R01/R37HD41900."} +{"text": "There are a number of errors in Tables S1 Table(XLSX)Click here for additional data file."} +{"text": "The uploaded S1 FileParameters measured for each subject of the database.(XLSX)Click here for additional data file."} +{"text": "In the Data Availability Statement, the GenBank ID is listed incorrectly. The correct statement is: The novel cDNA and protein sequence of the GTF2I-BRAF 19\u201310 fusion gene has been deposited to GenBank (BankIt) at NCBI under Accession Number KY884638."} +{"text": "The following information is missing from the Funding section: This study was supported by the UCLA CFAR Gene and Cellular Therapy Core Facility (UCLA Center for AIDS Research NIH/NIAID 5P30 AI028697)."} +{"text": "Elizabeth Blackwell Institute early career fellowship and by the Wellcome Trust International Strategic Fund ISSF2: 105612/Z/14/Z.The authors regret that the following funder acknowledgement was not clearly made: MJK was funded by an The authors would like to apologise for any inconvenience caused."} +{"text": "The following information is missing from the Funding section: This study was supported by the Italian \"Ministry of Health\" via CUP number H91J11000220001."} +{"text": "The member list of the REHAP Investigators is missing from the Acknowledgements section. The full member list has been included in the Supporting Information file S1 File(DOC)Click here for additional data file."} +{"text": "There is an error in the legend for Figure 9. \"(C)-(D) same as (A)-(B) for the model (mean only)\" should instead read \"(B),(D) same as (A),(C) for the model (mean only)\".The publisher apologizes for this error."} +{"text": "The files published for S1 Fig(TIF)Click here for additional data file.S2 FigOperations of municipalities aggregated at the state level. Considerable spatial hetegonenity in the number of loan pleas by federated entity can be observed.(TIF)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: DK is an Economic and Social Research Council (UK) postdoctoral fellow (ES/P009735/1)."} +{"text": "The following information is omitted from the Funding section: This research has been conducted using the UK Biobank Resource under Application Number 8256 and supported in part by Medical Research Council grant MR/N025083/1."} +{"text": "The graphical abstract is omitted from the list of Supporting Information. It can be viewed below.S1 File(DOCX)Click here for additional data file."} +{"text": "Due to a technical error during the production process the article was originally published with incorrect bibliographical information. The article has been updated with the following correct bibliographical information:Living Rev Relativ (2016) 19:3Received: 4 December 2015Accepted: 21 July 2016Published online: 17 February 2017The earlier version incorrectly identifying the article as Living Rev Relativ (2016) 19:1 should be disregarded."} +{"text": "In the original version of this article [1], published on 4 April 2018, there was 1 incorrect author family name. The redundant affiliation (5) has also been removed. The original article has been updated.Kari GalvinThe incorrect author name was published as:Kari GlavinThe correct author name are:The original publication of this article has been corrected."} +{"text": "The initially published PDF copies of the Supporting Information are provided below.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file."} +{"text": "The following information is missing from the funding section: This study was supported by NIH grant 5T32GM008203 to EP."} +{"text": "In S2 TextExplanation of methodology for inferring fragment-specific error parameters in the optional BAM mode of DICE.(PDF)Click here for additional data file."} +{"text": "The equation in the file S1 Appendix(DOC)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This study was supported by the project Instituto de Salud Carlos III (FIS PI15/01114)."} +{"text": "The following information is missing from the Funding section: SJD is supported by the Biotechnology and Biological Sciences Research Council (BBSRC grant number BB/K002260/1)."} +{"text": "The Data Availability statement for this paper is incorrect. The correct statement is: Data is available at NCBI sequence read archive (SRA) under accession number SRP125165."} +{"text": "The Supporting Information section is omitted. The publisher apologizes for the error. Please view the Supporting Information section here:S1 TextThis file includes supplementary data.(PDF)Click here for additional data file."} +{"text": "The authors wish to add the following acknowledgement to the article:\u201cThis research was conducted under the auspices of the Austrian National Election Study (AUTNES), a National Research Network (NFN) sponsored by the Austrian Science Fund (FWF) (S10902-G11)\u201d."} +{"text": "The affiliations for authors Liguo Zhang and Wei Li are incorrect. Liguo Zhang and Wei Ling are not affiliated with #1 but with #2 Heilongjiang Academy of Agricultural Sciences, Harbin, China."} +{"text": "The following information is missing from the Funding section: A mass spectrometer used in this study was purchased using NIH Shared Instrumentation Grant 1S10OD020062-01."} +{"text": "Part of the data are not included in the Supporting Information file S1 Table(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: This work was supported by Spanish MINECO and the European Regional Development Fund (ERDF) grant CONSOLIDER INGENIO 2010 CSD00065 (A.G.E)."} +{"text": "The following information is missing from the Funding section: The authors acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Fund of Charit\u00e9 \u2013Universit\u00e4tsmedizin Berlin."} +{"text": "Unfortunately, the original version of this article did not \u2018This research was supported by the Global Innovative Research Center (GiRC) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012K1A1A2A01056093).\u201d"} +{"text": "Nature Communications7: Article number: 13874 ; DOI: 10.1038/ncomms13874 (2016); Published 12222016; Updated 09062017The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the National Institutes of Health grants R01GM098749 and National Institutes of Health Transformative Research Award R01NS096786."} +{"text": "Scientific Data 4:170052 doi: 10.1038/sdata201752 (2017); Published 25 April 2017; Updated 1 August 2017The financial support for this Data Descriptor was not properly acknowledged. The Acknowledgements section should have recognised a grant from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning of the Government of South Korea (grant no. 2017R1A2B2006032)."} +{"text": "The graph B2 in S2 FigTornadoplot for estimated transmission parameter (1), percentage contribution to LTBI from TB transmission within the Netherlands (2), from immigration (3), or from travel to country of origin (4) for Moroccan (A), Turkish (B) and Indonesians (C). Percentage deviation from the estimate in main text (Table 2) is given for the minimum and maximum values for the parameters in Table 1 in the main text.(PDF)Click here for additional data file."} +{"text": "Table S3 is incomplete. Please view the complete file here: Click here for additional data file."} +{"text": "The first four columns in Table S1 were missing . The correct version of Table S1 can be viewed here: Click here for additional data file."} +{"text": "The bottommost graph in Figure S6 is labeled incorrectly. It should read: Input Signal (n=1). The file extension for the figure is also incorrect. Please view the correct figure here:"} +{"text": "In the Materials and Methods subsection \"Characterization of the stimulatory clone 52B7,\" the second sentence of the last paragraph was incorrect. The correct sentence should read: \"One hundred and ninety two transposed clones of 52B7 were picked and tested for a revertant phenotype toward NF-\u03baB activation.\""} +{"text": "A funding source was omitted from this article. Part of this work was financed by the ARC (Association pour la Recherche sur le Cancer), grant A08 / 5 / 1062 to MH."} +{"text": "An incorrect version of Table S1 was published. The correct Table S1 file can be found here:Click here for additional data file."} +{"text": "The following information was missing from the Funding section. This study was supported by NIH/NIAID grant 1UO1-AI062636."} +{"text": "To the Editor: Recent reports of cats positive for H5N1 type A influenza virus , a common antigen of type A influenza viruses, expressed by both avian and human strains (Serologic tests for antibodies to type A influenza virus were performed with a competitive ELISA to detect NPA antibodies (All cats were negative for type A influenza virus antibodies. The ELISA we used has been validated in several species, including humans ("} +{"text": "An incorrect version of Dataset S1 was presented. The full Dataset S1 file can be found here:Click here for additional data file."} +{"text": "The file for Table S2 is incorrect. Please view the correct file at: Click here for additional data file."} +{"text": "There was an error in Figure 1. Panel (B) was not included and panel (C) was incorrectly labeled as (B). The corrected figure is available here:"} +{"text": "The Table S3 link leads to an incorrect file. Please view the correct Table S3 here:Click here for additional data file."} +{"text": "The incorrect table was published in place of Table S2. The correct table can be viewed here: Click here for additional data file."} +{"text": "The published Table S2 is the incorrect version. Please view the correct table here:Click here for additional data file."} +{"text": "For patients 22 and 37 the clinical parameters are incorrect. Please view the corrected table here:Click here for additional data file."} +{"text": "The Supporting Information text file does not appear. It should be cited as \"Text S1\", with a caption \"Mathematical modeling and derivation of analytical expression, and supplementary figures legends\". Please view Text S1 here: Click here for additional data file."} +{"text": "In Text S1, some taxonomic names were incorrectly specified. The taxonomic corrections of Text S1 are based on the phylogeny of Figure S3. Please view the correct Text S1 here: Click here for additional data file."} +{"text": "The file for Dataset S4 is a duplicate of Dataset S3. Please view the correct file for Dataset S4 here:Click here for additional data file."} +{"text": "The following information was omitted from the Funding section: These studies were supported in part by the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement U01-HD060496 (to MMM)."} +{"text": "A file was unintentionally omitted from the Supporting Information section of the published article: \"Text S1. Training data.\" The file can be viewed here: Click here for additional data file."} +{"text": "The following information was missing from the Funding section: Additional funding was provided by NIH grant 5R01DK081587-01."} +{"text": "In Text S2, the references are missing. Please view the correct Text S2 here: Click here for additional data file."} +{"text": "Table S7 is incorrect. The correct version can be viewed here: Click here for additional data file."} +{"text": "In the Funding section, the second grant number from the NIH Models of Infectious Disease Agent Study program was incorrect. The correct grant number is: 1U54GM088558."} +{"text": "The hyperlink to Supplementary Figure S2 connects to the wrong document. Please view the correct Figure S2 here:Click here for additional data file."} +{"text": "The following information is missing from the Data Availability statement: Raw data supporting Fig 4 and S1 Fig are found in the S1 File(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Data Availability statement: NS5B sequences have also been deposited to GenBank under accession numbers LC484047-LC484058 and LC506601."} +{"text": "The authors regret that the published article contained an error in Eqs. (2) and (3). The correct equations should be:The authors would like to apologise for any inconvenience caused."} +{"text": "Following publication of this article , concernHere the authors provide a revised The original images and the nerve fiber density and length data underlying the panels in S1 Table of the original article reports a gene expression array experiment. The data from the microarray experiment have been deposited at GEO, accession number [GSE130393]. The data underlying the other figures are no longer available.S1 File(TIFF)Click here for additional data file.S2 File(TIFF)Click here for additional data file."} +{"text": "There is an error in The authors provide the following methodological clarification: Some Western blot \u03b2-actin loading control images are duplicated within the figures Click here for additional data file.S2 FileRaw data for (RAR)Click here for additional data file.S3 FileFurther raw data for (RAR)Click here for additional data file."} +{"text": "The macro included in the Supporting Information file, S1 Macro(XLS)Click here for additional data file."} +{"text": "HB40 gene are duplicated. The authors have provided the correct version of There is an error in S4 Table(XLSX)Click here for additional data file."} +{"text": "In Table 3, all the means (SEs) and medians (interquartile ranges) should have been labeled as adjusted. This article has been corrected.1In the Original Investigation titled \u201cEffect of Exposure to Gun Violence in Video Games on Children\u2019s Dangerous Behavior With Real Guns: A Randomized Clinical Trial,\u201d"} +{"text": "The correct email address for Sun-Joon Bai is: The underlying data for this study is omitted from the article. The authors have now provided the dataset. The underlying data can be viewed in S1 Dataset below.S1 Dataset(XLSX)Click here for additional data file."} +{"text": "The following information is missing from the Funding statement: This study was supported by the Social Science Korea (SSK) Project through the NRF funded by the Ministry of Education, Republic of Korea (Grant number: 2017S1A3A2067165 to Y. Youm)."} +{"text": "The units for the vertical axis for panels K and L should be: zmol PSII cell-1. Please see the correct In"} +{"text": "This system has been extensively tested in the lab and validated in field studies. Comparing measurements obtained with the use of the new passive sampling system with equivalent measurement with the use of an active filter pack H2S sampler yielded an accuracy of greater than 85%. The new H2S passive sampling system can be used to measure ambient H2S concentrations ranging from 0.02 to 7 ppb based on a 1-month exposure period. There is no significant interference found from other sulfur compounds in air. This system has been used in many air monitoring projects.A new Maxxam All-Season Passive Sampling system for monitoring H2S in air has been developed. This passive sampling system employs the same approaches as the Maxxam All-Season Passive Sampling Systems for monitoring SO"} +{"text": "Ahmed that was accidentally missed. The publisher apologizes for the error.This article was republished on April 11S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file."} +{"text": "Dr. Cui\u2019s email address is: There is an error in With this Correction, the authors provide the underlying image files for Figs S1 FileThis file contains underlying image data for Figs (ZIP)Click here for additional data file."} +{"text": "Nature Communications 10.1038/ncomms15700; published online 16 June 2017Correction to: The original version of this Article omitted the following from the Acknowledgements:\u2018This project was supported by CRC128/Project A03 of the Deutsche Forschungsgemeinschaft (DFG).\u2019This has not been corrected in either the PDF or HTML versions."} +{"text": "There are errors in the Funding statement. The correct Funding statement is as follows: This work was supported by the National Research Foundation (NRF) of Korea Grant funded by the Korean Government (MSIT) (2019R1G1A1006073)."} +{"text": "In the Funding section, one of the grant numbers from the funder Instituto de Salud Carlos III (ES)\u2014European Regional Development Fund is listed incorrectly. The correct grant numbers are: PI 12/01142 and PI 15/01311."} +{"text": "The supplementary dataset is omitted from the list of Supporting Information. It can be viewed below as S1 File(CSV)Click here for additional data file."} +{"text": "There is an error in the data presentation of Supporting Information file S2 TableDifferences regarding WHtR categories. Z test proportions. The differences are between the same gender groups.* p<0.05.(DOCX)Click here for additional data file."} +{"text": "Scientific Reports 10.1038/srep15204, published online 06 November 2015Correction to: The original version of this Article contained an error where Supplementary Data 10 was a duplication of Supplementary Data 11. This error has now been corrected in the Supplementary Data that accompanies this Article."} +{"text": "The Program for Medical Key Department of Shanghai (no: ZK 2015B17);2. The Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (no: PWZxq2017\u201311)."} +{"text": "Scientific Reports 10.1038/s41598-018-29363-0, published online 20 July 2018Correction to: This Article contains typographical errors in the Acknowledgements section.\u201cAuthors KHK and RSM are indebted to Global Frontier Program through the Global Frontier Hybrid Interface Materials (GFHIM) of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2013M3A6B1078869) for financial support.\u201dshould read:\u201cAuthors KHK and RSM are indebted to Global Frontier Program through the Global Frontier Hybrid Interface Materials (GFHIM) of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2013M3A6B1078874) for financial support.\u201d"} +{"text": "Following publication of this article , concernIn In In In The authors acknowledge that in Figs A revised A revised The underlying blots for Figs S1 File(ZIP)Click here for additional data file."} +{"text": "After this article was corrected and republished , 2 to adThe authors explained that these images were cropped incorrectly when the original figure was composed such that they included control lanes Click here for additional data file.S2 File(XLS)Click here for additional data file.S3 File(PDF)Click here for additional data file."} +{"text": "The graph for S4 FigMaster\u2013apprentice relations among Nobel laureates in Chemistry (North America). Underlined names are from other regions.(EPS)Click here for additional data file.S5 FigMaster\u2013apprentice relations among Nobel laureates in Physiology or Medicine (Europe). Underlined names are from other regions.(EPS)Click here for additional data file.S6 FigMaster\u2013apprentice relations among Nobel laureates in Physiology or Medicine (North America). Underlined names are from other regions.(EPS)Click here for additional data file."} +{"text": "The toxic threshold concentration values for Sunitinib and Imatinib are swapped in The toxic threshold concentration and safety margin values for Sunitinib and Imatinib are also incorrect in S1 Table(DOCX)Click here for additional data file."} +{"text": "There are a number of errors in the caption for The caption listed within Supporting Information file Note, there is an error in the caption for S1 Text(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file."} +{"text": "After publication of this article , concernThe authors provide a revised version of S1 File(TIF)Click here for additional data file.S2 File(TIF)Click here for additional data file."} +{"text": "The data underlying Table 2 are omitted from the list of Supporting Information. The data can be viewed below.S1 FileThis file includes the data underlying Table 2.(XLSX)Click here for additional data file."} +{"text": "The ninth author\u2019s name is spelled incorrectly. The correct name is: Jun Nyung Lee.In the Funding Statement, one of the grant numbers from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) is missing: 2019R1F1A1062343 for SS."} +{"text": "This article has been corrected.1In the Original Investigation titled \u201cAssessment of Health Care Utilization and Cost of Targeted Drug Delivery and Conventional Medical Management vs Conventional Medical Management Alone for Patients With Cancer-Related Pain,\u201d"} +{"text": "There are errors in the caption for S1 File(XLSX)Click here for additional data file."} +{"text": "There is an instance of data duplication in the Supporting Information item Please view the corrected version of S1 File(XLSX)Click here for additional data file."} +{"text": "The publisher apologizes for the errors.S1 Table(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file."} +{"text": "The supporting information item The final, peer-reviewed version of The publisher apologizes for this error.S1 Code(ZIP)Click here for additional data file."} +{"text": "Giardia and Cryptosporidium. In this correction article the updated additional file (Additional file In the original publication of this article the suppAdditional file 1: Table S1. Updated polymerase chain reaction conditions for detection of Giardia and Cryptosporidium."} +{"text": "The authors also provide raw data underlying The authors provide an updated PLOS ONE article [Antonie Van Leeuwenhoek article [PLOS ONE article [Antonie Van Leeuwenhoek article [Antonie Van Leeuwenhoek article [Moreover, the authors reused Fig 2A from the article in the A article in the A article . The autS7 FigPLOS ONE article as picl1 panel, these lanes represent experimental results for the pdnaA panel as reported in [Note that the data shown in the upper row (lanes 11\u201318) correspond to the data that were originally and mistakenly used in the orted in (this is(TIF)Click here for additional data file.S8 Fig(TIF)Click here for additional data file.S9 Fig(TIF)Click here for additional data file."} +{"text": "The following information is missing from the Funding statement: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1F1A1058719 and 2019R1G1A1006073). The publisher apologizes for the error."} +{"text": "The Data Availability statement is incorrect. The raw data underlying the study are not provided in the published paper and its Supporting Information files. The authors have provided the data as Supporting Information file S1 File(CSV)Click here for additional data file."} +{"text": "The Health Research Fund (FIS) grant number is missing. The correct grant number is PI18/00045."} +{"text": "The data in the S2 Data File(XLSX)Click here for additional data file."} +{"text": "Article ID: pez511Table 2 has been updated to remove first two rows showing r and P values of correlations for wheat vs wheat, and last two columns showing r and P of correlation for animal fat vs animal fat. All the r and P values between same ingredients are now removed where P values in the original Table were incorrect."} +{"text": "The correct name is Arpad Todor. The correct citation is: Todor A (2018) Willing to pay to save the planet? Evaluating support for increased spending on sustainable development and environmentally friendly policies in five countries. PLoS ONE 13(11): e0207862."} +{"text": "The following information is missing from the Funding statement: This study was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Charit\u00e9 \u2013Universit\u00e4tsmedizin Berlin."} +{"text": "The following information is missing from the Funding section: This study was funded by the National Evidence-based Healthcare Collaborating Agency (Grant Number: HC16C2299)."} +{"text": "The intervention type consisted of an experimental group (REDStory) and a control group (wait-list control group). The study participants were randomly assigned to either wait-list control group or experimental group by 3 of the researchers.The 2.5 Procedure should read: This study adopted a group randomized controlled trial design,"} +{"text": "The authors have provided an updated version of S2 Table(XLS)Click here for additional data file."} +{"text": "The following information is missing from the Funding section: The work was conducted using the facilities of the Roslin Institute funded by the BBSRC. NS is supported by BBSRC through the Institute Strategic Programme funding (BB/J004235/1 and BB/P013740/1)."} +{"text": "In the above named article [1] the details for the Financial Support section are incomplete. The complete details are as follows:This work was supported by the Spanish Health Research Fund (Fondo de Investigaci\u00f3n Sanitaria) (PI96/0201) and the \u2018Carlos III\u2019 Institute of Health (PI15CIII/00037).The authors apologise for this omission."} +{"text": "The following information is missing from the Funding statement: This study was supported by Deutsche Forschungsgemeinschaft and Universit\u00e4t Rostock within the funding programme Open Access Publishing (to RU)."} +{"text": "The data underlying this study were omitted from the original article. The authors have provided the complete dataset below as S1 File(XLSX)Click here for additional data file.S2 File(XLSX)Click here for additional data file."} +{"text": "The originally published, uncorrected article is provided here for reference.S1 File(PDF)Click here for additional data file."} diff --git a/PMC_clustering_224.jsonl b/PMC_clustering_224.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..dd6e16bd61fa96ada170aba74ac591c2e289a459 --- /dev/null +++ b/PMC_clustering_224.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:395b6ce992ce71fa610457d83f35909080a345799ffb38ed473a37e28cd086f8 +size 111339474 diff --git a/PMC_clustering_225.jsonl b/PMC_clustering_225.jsonl new file mode 100644 index 0000000000000000000000000000000000000000..277a84603cf97d275bf84e8a2d94a40e4df59cce --- /dev/null +++ b/PMC_clustering_225.jsonl @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid 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0000000000000000000000000000000000000000..ee5c3c81bfda701aa6de1cca193273d9bfffee0f --- /dev/null +++ b/PMC_clustering_253.jsonl @@ -0,0 +1,1292 @@ +{"text": "It was highlighted that in the original article the given and family name of the first author was interchanged and thus tagged incorrectly. This Correction article shows the correct name order. The original article has been updated."} +{"text": "The standard deviations in column 1 are incorrect due to a copy/paste error. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to this paper : The proTo the correct version, as follows:The authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "In the original article, there were several errors throughout the text. The corrections made are detailed in the table below.The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to their published paper . The secThe correct Figure 5B should be as below:Nutrients for this mistake. The change made does not affect the results. The published version will be updated on the article webpage with a reference to this Correction.The authors would like to apologize to the readers of"} +{"text": "Insects Editorial Office and in agreement with the authors, the paper will be removed from the public record and marked as retracted. We apologize for any inconvenience caused by the removal of this article.The published article has beenInsects is a member of the Committee on Publication Ethics (COPE) and strives to uphold the highest ethical standards. The article [ article is retra"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make a correction to their published paper .In The change does not affect the review results.The rest of the manuscript does not need to be changed. The authors would like to apologize for any inconvenience caused. The manuscript will be updated, and the original will remain available on the article webpage."} +{"text": "The authors regret that these errors were allowed to enter into the published version of this article, and apologize to the readership for the inconvenience caused."} +{"text": "The publisher apologizes to the authors and readers for the error. When citing this work, please refer to the original version."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Concerns have been raised about the integrity of the data reported in this article . This is"} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in the Data Availability Statement. The correct data accession number is PRJCA003775.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "It was highlighted that the original publication erroneously contained the galley proof instead of the final version of the article. The Publisher would like to apologize to the authors and readers for the inconvenience."} +{"text": "Furthermore, they apologize to the readership for any inconvenience caused.The authors regret the error that was made in the preparation of the published figure, and confirm that this error did not affect the conclusions reported in the study. The authors are grateful to the editor of"} +{"text": "The author wishes to make the following corrections to this paper . The reaThe correction does not change the conclusions of this manuscript. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "As elaborated in the excellent paper by Haahr et al. the POSEThe paper by Haahr et al. is preseVB prepared the manuscript. RF reviewed the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We apologize for any inconvenience caused to the readers by these errors. The manuscript will be updated, and the original will remain online on the webpage for the article including a reference to this Correction."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Natural Science Foundation of Hebei Province (No. H2018206310).In the original article, there was an error in the Funding statement. The correct name for the funder is The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper : In the The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The authors wish to make the following corrections to this paper : in the The authors apologize for any inconvenience caused and state that other scientific information is unaffected. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the legend for In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :The 33 references in And should be replaced with the following version:The authors would like to apologize for any inconvenience caused to the readers by these changes. The original article has been updated."} +{"text": "In the original article, there was a mistake in There was also a mistake in the legend for The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The publisher has been alerted to potential errors in the stated probiotic composition of the product used in this study. This statement will remain while an investigation is underway and will be updated and any necessary corrections made at the conclusion of the investigation."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in the order of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :The manuscript contains one mistake, namely, The correct The authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "The Editorial Office and the authors have taken the decision to retract the published article . The WesMDPI is a member of the Committee on Publication Ethics and takes seriously its responsibility to publish only high-quality research. We regret that this issue was not identified earlier and apologize to readers of the journal."} +{"text": "The corrected **** appears below.In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were four mistakes as published, respectively, letters for Duncan's multiple range test was assigned wrongly in The corrected The corrected The corrected The corrected We are deeply sorry for the trouble our mistake has caused readers. There is no effect on the paper except for the error in the letter marking of the original article.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the title. The correct title of the article is Molec"} +{"text": "The authors would like to correct an error in a recent published paper . Due to The authors apologize for any inconvenience caused to the readers by the change. The change does not affect the scientific results."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the legend for In the original article, there were also mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "These figures did not have any statistical markers or correct headings. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The originally published figure had a panel out of order. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : The authors would like to apologize for any inconvenience caused to the readers by these changes.The authors wish to make the following correction to this paper : Due to with"} +{"text": "The authors would like to retract this paper on the basis that the correct South African Department of Health protocols for communications relating to this body of work were not followed. Their full statement is as follows:We (the co-authors) have discussed the article with the Department of Health and a collective decision has been reached that we would like the entire article retracted on the basis that some of the information on MhINT that was divulged had overstated the scope covered through MhINT for Department of Health and should thus should not have been included \u2013 making aspects of the MhINT content of the editorial currently inaccurate and potentially misleading."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper .The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :There was a mistake in the original version of the article in should be replaced with the following version:Thus, the original Figure 2 listed below:The authors state that this correction does not modify the scientific results of the study. The authors would like to apologize for any inconvenience caused by this mistake."} +{"text": "This article is being retracted from Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the authors to common features in the FACS plots of Figure 1.The authors have been unable to replicate the results, hence felt it was necessary to retract the paper. The Editorial Board agrees to the retraction."} +{"text": "Here, in some cases the wrong numbers were entered. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the legend for Figure 4 as published. The legend contained an incorrect wrong reference which was added by mistake. The reference has been removed from the legend.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, we neglected to include the funder the Italian Ministry of Health .The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We wish to report an error in the title of article . The cor"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We show that this simpler setting yields a polynomial complexity of the learning process. Both of the algorithms are implemented and evaluated on a collection of randomly generated examples. We furthermore demonstrate the simpler algorithm on the functional specification of the TCP protocol.We present an algorithm for active learning of deterministic timed automata with a single clock. The algorithm is within the framework of Angluin\u2019s"} +{"text": "We apologize for the errors and for any confusion it may have caused.In the published article"} +{"text": "All the authors agree to this retraction. The authors apologize to the readership of the Journal for any inconvenience caused.The Editor has agreed to the authors' request, and therefore this article has been retracted from"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the labeling three sub-headers of the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. All the raw data is still available at the Supplementary Table S2."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in the Acknowledgments section. The selected icons used for Figure 1 with permission under the free license were sourced from two icon supply websites which have transferred ownership. As the current content on the websites have no relevance to our research, we have removed the respective links and the Acknowledgments section.The authors state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret that there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in In addition, the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors found that The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper in the tThe table should be replaced with the following We stress that these errors were purely due to human error and oversight, all corrections done do not change the written portion of the table, or the final conclusion of this manuscript. The manuscript will be updated. The authors would like to apologize for any inconvenience caused. All changes have been reviewed and approved by the Academic Editors."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The data for the tumor volume and survival results has also now been published as"} +{"text": "In addition, there were irregular clusters of dots between the two adjacent groups of LN in In the original article, there were errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The recovery measures announced by Europe in parallel with the Green Deal are the perfect opportunity to step up the effort to measure the impact of public expenditure, both in the short and in the long term. To that aim, it is essential to quickly stabilise benchmarks to measure the financial and non-financial impact of investments in the European recovery plan."} +{"text": "In the published article, there was an error in the order of the affiliations. Affiliation 1 and 2 have now been switched with the correct order appearing above.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "VIROPLANT project which has received funding from the European Union's Horizon 2020 Research and Innovation Program is 773567.There is an error in the Funding statement. The correct number for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make an erratum to the published version of his paper . In the"} +{"text": "Due to an oversight by the authors, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The first funding number should be The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, the figure legends were associated with the wrong figures. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected author list is shown above. The authors regret that the name of the seventh author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused."} +{"text": "There is an error in the title. The correct title of the paper is \u2018Blan"} +{"text": "In the original article, there was a mistake in the motility assay in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "As elaborated in the excellent paper by Haahr et al. the POSEThe paper by Haahr et al. is preseVB preparation of manuscript. RF revision and completion. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The correct one should be The authors apologize for the error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper . Due to withThe author would like to apologize for any inconvenience caused to the readers by these changes. This change will not affect the results of the article."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper . Due to with:The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Kaiqi Shao should not have been included as a corresponding author in the published article. Fei Lei was the sole corresponding author of this article.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Nanomaterials. The decision to retract has been taken in agreement with the authors.One of the contributors to the published paper did not MDPI is a member of the Committee on Publication Ethics and takes the responsibility to uphold strict ethical policies and standards very seriously."} +{"text": "After publication of the original article , the autThe original article has since been corrected with the complete version of the affiliation, and the complete affiliation can be found in this correction."} +{"text": "The dotThe manuscript will be updated, and the original will remain online on the article webpage, with a reference to this correction. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "PLOS ONE to clarify that they did not obtain prospective institutional review board approval to conduct their study. Upon editorial review and consultation with the Academic Editor, it was determined that the article meets the journal\u2019s standards for ethical oversight and that approval by an ethics committee was not necessary given that all data analyzed in the study were fully anonymized prior to access and analysis by the authors.After publication of this article , the autIn light of this update, the final two sentences of the second paragraph in the Study design and population subsection of the Materials and methods are incorrect. The correct sentence is: All data analyzed in the study were fully anonymized prior to access and analysis by the authors."} +{"text": "The authors are grateful to the Editor for allowing them the opportunity to publish this Corrigendum, and wish to apologize to the readership of the Journal for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and please note that the replaced images do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : in FiguFigure 4with the new The article conclusions and findings reported are not affected by this correction. All authors approve this correction. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "This article is being retracted from Bioscience Reports at the request of the authors.The authors have been unable to replicate the results produced in the study, in particular the quantity of podocytes undergoing apoptosis following treatment with Triptolide (TPL), causing the authors to doubt the original conclusion that TPL has no influence on the cell viability and apoptosis. The authors are still investigating the mechanism of TPL regulation on podocyte lesions and the reason for this discrepancy is currently unknown.The authors also note that there are errors in the units throughout the paper, as well as a \u201cGlucose treatment and cell culture\u201d section in the methods, which did not form part of this study. The Editorial Board agrees to the retraction."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In our recently published article we noticed that we presented incorrect information in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : in the We apologize for the original error. To correct this oversight, Schirmann et al., 2009 [The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated."} +{"text": "Introduction. It has now been removed.In the original article, the reference to the study by The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the legend for In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that these corrections do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper . Due to withThe authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "The authors wish to make the following changes to their paper . Due to to:Cells.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. All changes have been reviewed and approved by the Academic Editors of"} +{"text": "The authors wish to make the following corrections to this paper :The authors would like to replace Table 3 in . The corand should be replaced with the following The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Following the publication of this article , concernThe bands presented in Fig 6A appear to have been spliced from the underlying gel and arranged into Fig 6A as presented in the published article. The preparation and presentation of the bands raises concerns regarding the reliability of the data presented in the published figure. The authors have informed the journal that the uncropped blots for Fig 6A are no longer available.The authors have indicated that the original data underlying other results from this study are also not available. In light of this, the article is not in compliance with the journal\u2019s Data Availability policy in place at the time of the article\u2019s publication.PLOS ONE Editors issue this Expression of Concern to notify readers of the unresolved concerns pertaining to the reliability of the data presented in Fig 6A and the unavailability of underlying data to support the results presented in the article.The"} +{"text": "The authors replied to the Editorial Office to explain that errors were made during the process of uploading the images, and also to request a retraction of the paper.Oncology Letters has concurred that this article should be retracted, and all the authors agreed with the retraction. The Editor apologizes to the readership for any inconvenience caused.The Editor of"} +{"text": "In the original article, there was a mistake regarding references in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper . In TablwithThe conclusions continue to remain the same. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original Supporting Information, we missed The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to Figure 6B of this article : the merThe authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "The reason for this retraction is an inability to be able to replicate certain of their previous results, and also disagreements among the authors as to the interpretation of some of the data. Following further discussion, all authors and the Editor of"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to this paper . The reaThe correction does not change the conclusions of this manuscript. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The publisher regrets that the order of authors was incorrect at the time the article was published. This has now been corrected.The publisher would like to apologise for any inconvenience caused."} +{"text": "This has now been corrected in the HTML version of the Article. The PDF version of the Article was correct at the time of publication."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figure 3 as published. On The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : replaceThese changes have no material impact on the conclusions of the paper.The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, part of Figure 1 was included in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original version of the article , the sur"} +{"text": "In the published article it should have been indicated that Caroline Gabrysch was a corresponding author.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article there is an error in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to correct an error in the title paper . This erThe authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to correct the following erratum in this paper .The contributions for the second author (Costan G Magnussen) and the fifth author (Bo Xi) were not fully stated in \u201cAuthor Contributions\u201d section. Both authors have made substantial contributions to analysis and interpretation of data for the work; AND revising the work critically for important intellectual content; AND final approval of the version to be published; AND agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved."} +{"text": "There is an error in the Acknowledgment statement. The correct number for project number is 175042.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :y-axis. The version of The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Lei Yin and Huan Huang. The correct order is Huan Huang and Lei Yin.In the original article the author order was incorrectly given as The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :The authors would like to replace Figure 3b in . The corand should be replaced with the following Figure 3b:The authors would like to replace the first affiliation in . The oriThe authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The correspondence order was incorrect in the original article. The lead contact author should be Xinyuan Ding.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : the hemThe authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected versions of Oncology Letters and to the readership for any inconvenience caused.After the publication of the above article, the authors have realized that"} +{"text": "The chaThe authors and the Editorial Office would like to apologize for any inconvenience caused to the readers by these changes. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In the original article, there was a mistake in In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make the following correction to our recent publication . In the This study is a subset of a larger observational study. Initially, we determined the sample size for a correlation between DXA and QUS using a The authors would like to apologize for any inconvenience caused by this amendment. This amendment does not affect the results or conclusion of the manuscript in any way."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We omitted Natural Science Foundation of Guangdong Province from Acknowledgments, and we updated it as below. We apologize for the errors and for any confusion it may have caused.In the published article"} +{"text": "In our article In addition, the description of the whole section regarding all the supported grants originally stated in the acknowledgements in the initially published version of this article The corrections made in this erratum do not affect the original conclusions. The authors apologize for any inconvenience or misunderstanding that these errors may have caused."} +{"text": "In the original article, there were mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This is now corrected in a new deposition in the Protein Data Bank, The authors would like to apologize for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the original article, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper . Due to These changes have no material impact on the conclusions of our paper. The authors apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake. The incorrect The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "It has come to our attention that the majority of the content in the title paper was copiSensors for any inconvenience caused. MDPI is a member of the Committee on Publication Ethics and takes the responsibility to enforce strict ethical policies and standards very seriously. To ensure the addition of only high-quality scientific works to the field of scholarly publication, is retra"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Furthermore, they apologize to the readership for any inconvenience caused.The authors regret the error that was made in the preparation of the published figure, and confirm that this error did not affect the conclusions reported in the study. The authors are grateful to the editor of"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "It has been brought to our attention that the methods and results presented in are almoSensors.MDPI is a member of the Committee on Publication Ethics and takes seriously its responsibility to publish only high-quality research. We regret that this was not discovered prior to publication and offer our apologies to the readers of"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We apologize for the errors and for any confusion it may have caused.In the published article"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to the paper . Due to withThese changes have no material impact on the discussion and conclusions of the paper. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The authors would like to make the following corrections to this paper :We have found two typographical errors in Equation (1) and we wish to replaceWithPeff heading in Peff value for levofloxacin increases . For these reasons, the authors wish to replace We have found a typographical error in the WithThese changes do not affect the discussion and conclusions of the study. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make a correction to the published version of their paper . The wor"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the Funding statement. The correct number for National Nature Science Foundation of China is 31772547, 31702211.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected **** appears below.In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , it was The name has since been updated in the original article and the (correct) name may be found in this correction.The authors apologize for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the initially published version of this article, the IHC image of the Akt expression of the PMA group in Figure The corrections made in this erratum do not affect the original conclusions. The authors apologize for any inconvenience or misunderstanding that this error may have caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The correction reported in the following has to be applied to the paper .Due to an unexpected result of the conversion procedure, the old Figure 8a:needs to be replaced with the following:This change does not affect the results and conclusions of the paper. The authors would like to apologize for any inconvenience caused to the readers."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office never received a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to"} +{"text": "The authors would like to make the following corrections to this paper .In the original article, there was a mistake in Table 2. In the legend of Table 2, the indicators of a negative influence correspond to the number 1 and the indicators of a positive influence correspond to the number 2. The correct version of The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in the legend for In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original published version of this article, the authors did not mention the acknowledgements in the main manuscript. We have now added the acknowledgements. The authors apologize for the errors. Both the HTML and PDF versions of the article have been updated to correct the errors."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the Funding statement. Full information on the funding was not provided. The correct Funding statement appears below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article has been retracted due to concerns regarding the provenance of this article as well as the credibility of the case reported therein. Repeated attempts to contact the authors and their institutions were unsuccessful, leaving the journal with no choice but to retract the article in order to correct the academic record."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author. The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server."} +{"text": "However, the representative Western blot bands depicted at the bottom of the histograms are correct, as described in the original caption that is also reported below. The corrected In the published article, there was an error in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The original table is not shown in this corrigendum because the participant identifiers were changed to improve participant confidentiality. The only change is the values in the \u201cName\u201d column.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was a there was an error in There was also an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "Legend for In the published article, there was an error in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in Figure/TableIn the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corresponding author requested retraction of this article and statIn reviewing this matter, PLOS noted that the primary data were not provided with the published article , contrarPLOS ONE Editors issue this Expression of Concern to notify readers of the above issues which are unresolved as of the time of this notice.The"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The corrected The authors apologize for this error and state that this change has no impact on the results and conclusions of the article. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the caption for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were errors in The authors apologize for these errors and state that these mistakes do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were errors in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that some of the data in the above article were already under consideration for publication prior to its submission to"} +{"text": "The authors wish to make the following changes to their paper . In the The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the academic editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to"} +{"text": "Error in FigureIn the published article, there was an error in We apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in Figure 1 as published. In The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in We accidentally uploaded the wrong graphic during the production process after the proofing phase as we were trying to improve the resolution of the graphic. However, the legend and caption, as well as in the text explanations of the graph are based on the correct graph and the article was also reviewed and accepted with the correct graph.The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the Acknowledgments statement. Support from the University of Medicine and Pharmacy Carol Davila was not mentioned. The correct Acknowledgments statement appears below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was a typographical error in The author apologizes for this error and states that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the Funding statement as it was not specified that this research was funded by the Italian Ministry of Health Ricerca Corrente. The correct Funding statement appears below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way."} +{"text": "Due to a production error, there was a mistake in the legend for The original version of this article has been updated."} +{"text": "Due to a production error, there was an error in the published The publisher apologizes for this error. The original version of this article has been updated."} +{"text": "They also wish to apologize to the readership of the Journal for any inconvenience caused.After having re-examined their original data, the authors have realized that the data featured in"} +{"text": "In the original article The authors apologize for this error and state that it does not in any way change the scientific conclusions of the article. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in as publiThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "The Editorial Office identified that the figures and data provided in the articles original submission were correct, and that this error was introduced by the authors during the first revision. The authors state that this occurred due to copying and pasting the graphs when checking the alignment of the graphs in The requested correction and related raw data have been assessed and agreed by the Editorial Board. The authors declare that these corrections do not change the results or conclusions of their paper."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :In the original publication, there was a mistake in The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "This article has been retracted at the request of the authors. All authors consent to this retraction and together they have provided the following explanation:The members of the SAVE Program who were responsible for collecting and distributing the data used for Table 1 were not properly accredited. This also includes those involved in the execution of the program and the calling project. It is imperative that we maintain our integrity as members of the medical community, and allowing the article to remain accessible without properly crediting those essential to its creation would be an utmost violation of our values."} +{"text": "In the published article, there was an error in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We would like to thank for the comments of the letter to the editor about our article \u201cAbortion in Cases of Zika Virus Congenital Infection.\u201dWe agree with our colleagues about the statement that not all cases of maternal infection by the Zika virus have as a result a fetus with microcephaly. This was initially demonstrated by a series of cases of babies born with normal cephalic perimeter, despite the confirmation of infection of the mother.We believe that an early diagnosis provides the woman with a better understanding of the fetal situation, which empowers and enables her to decide what would be the best for her and the fetus, according to the law of each country."} +{"text": "In the published article, there was an error in The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The presentation will focus on elements of leadership that have been shown to be useful on local and more comprehensive levels. It will be based on experience gained in leadership positions in international and national organizations and during leadership and professional skills courses which were conducted in more than 40 countries over the past thirty years. Among the topics that will be addressed for discussion and further action will be the need to introduce leadership training in the course of postgraduate education and to provide career advice at the beginning and during early years of service.None Declared"} +{"text": "In the published article, there was an error in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in In the published article, there was an error in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The corrected Figure 1 and its caption appear below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in FigureIn the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in Figure/TableIn the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Table 2 was accidently provided for In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret that the title shown in the original article was incorrect. The correct title is as shown above.An independent expert has viewed the corrected title and has concluded that it is consistent with the discussions and conclusions presented.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article has been corrected at the request of the authors to add Jill David as first author. Due to some confusion among the authors, Jill David was originally omitted from the author list. She contacted the journal upon becoming aware of this and the authors agreed that this was an oversight."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were a few errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in Figure/TableIn the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make corrections to the reference citations in the original article . The autThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in the legend for \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Faiz Elfaki should appear as a corresponding author.In the published article, there was an error in the correspondence section. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, an error occurred in the representative immunoblot plot of TH in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to"} +{"text": "This article has been corrected to include a missing table and text that was accidentally deleted during the editing process. The journal greatly regrets that this error occurred and was not identified prior to publication. The erroneously removed section of the article consisted of the first three paragraphs of the Discussion section along with Table 1. This content has now been restored and can be found in the body of the article. Once again, the journal deeply regrets this error."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "After this article was publThe control panel is duplicated as the control + fingolimod panel in In the EAE panel in In response to queries about the experiments in In response to queries about the experiments in The original data underlying the control and control + fingolimod panels in The authors apologize for the errors in the published article.S1 File(ZIP)Click here for additional data file."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure\u00a06 was used as the image in In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in Figure/TableSR\u2019 was incorrectly positioned. The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figures. The figure for In the published article, there was an error in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, the order of the image files for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the author list. Fan Kangli and Zhao Hongguang are both equal and first authors.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original publication of the article, the last author name was misspelt. The correct name is given in this correction and the original article has been corrected."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, we would to like to add the merge relative to panel C1 and C2 of the Figure 2 as The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There was an error in the original publication . In all The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in Figs. 4 and 5 of the above article had already been published prior to its submission to"} +{"text": "In this third session of our motivational interviewing workshop, we address the art of persuasion and what to do and not do in the clinical setting. The change process in a motivational interviewing setting is based on collaborative principles between the patient and the therapist and is not imposed. We show examples of what to do and not to do with the previously learned techniques.None Declared"} +{"text": "In the published article, there was an error in The corrected In the published article, there was an error in The corrected In the published article, there was an error in The corrected The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in At the same time, the misused image is also used as part of the schematic diagram of the article. Therefore, corresponding correction have been made to the schematic diagram of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "This article has been retracted and removed due to a formal request from the family of the patients as formal consent was not obtained from the family prior to submission and publication.\u00a0The authors and hospital leadership have formally requested this retraction. Due to the privacy concerns of the family, the article contents have been removed as well."} +{"text": "Funding statement.In the published article, there was an error in the The article will no longer have a funding statement.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in Table 1 as published. The sequence of the LAMP internal backward and forward primers in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This is a peer review submitted for the paper \u201cA Framework for a Statistical Characterization of Epidemic Cycles: COVID-19 Case Study.\u201dIt seems that the aim of this submission is to reThe aim of the study should be stated in a precise statement with supportive ways to test the underlying hypothesis;Details of the analytical approach should be given with its assumptions and limitations;Sources of the data with overall reliability can be detailed;Use the appropriate and conventional terms of infectious diseases by checking the contents of the submission with reliable epidemiologists.I am satisfied with the modifications to the new version. Almost all of my concerns were addressed in the new version. I will let the readers decide about the validity of the model since the authors elaborated on the approach."} +{"text": "In the published article, there was an error in the legend for The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author of the manuscript is grate The author has added a correlation matrix to the supplemental materials.The author has added several examples of stepwise regression model use to the Introduction section to help ground readers in the validity of this approach in similar applications.The author has made the suggested points in the revised Limitations section of the Discussion. All data sets and regression model details have been added for each state to the Multimedia Appendices section. The author has changed the conditional formatting to red and blue in Figure 3."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper . In the The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in We apologize for this error and this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, an author name was incorrectly written as Turtuluci. The correct spelling is Turtulici.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the author list. Mengyu Li and Ning Li should share first authorship.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article has been corrected at the request of the authors to change Figure 1 to an updated version. In the initial published version of this article the data in the cholestyramine and placebo boxes were reversed. The authors deeply regret that this error was not identified and addressed prior to publication."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that some of the data in the above article had already been published prior to its submission to"} +{"text": "The authors would like to make the following correction to the published paper . The chaAdd this sentence to \u201cAcknowledgement\u201d section: The authors are grateful to the Deanship of Scientific Research and King Saud University for funding made available through the Vice Deanship of Scientific Research Chair.The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The reference appeared in the originally submitted version of the manuscript but was deleted in error during revision. It has now been restored in the article online."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We have now added O.D. as a corresponding author due to her role in providing resources and supervision for the study and her specialized contribution to the philosophical implications of our results. The change does not affect any of the other sections in the article or its conclusions. The authors apologize for any confusion caused to the readers."} +{"text": "The corrected order of Due to a production error, there was a mistake in The original version of this article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published prior to its submission to"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There was an error in the original publication in the dThe original equation was:The correct equation is:f0 used in the text were obtained using the equation and the correction does not change the claims or arguments of this paper.All The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the published article, there was an error in In the published article, an author name was incorrectly written as Sabbatini Roberto. The correct name is Roberto Sabbatini.The authors apologize for these errors and state that these do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The correct spelling is Kunling Song.In the published article, an The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in Figure/TableIn the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the Introduction, there is an error in the second sentence of the second paragraph. The correct sentence is: Cryptic exons contain parts of introns that are erroneously spliced into the mature mRNA."} +{"text": "The authors hypothesize that the phenotype may have been due to the variable nature of the filamentation assay.In addition, the authors have been unable to reproduce the finding that In light of these issues, the authors retract this article.All authors agreed with the retraction. We apologize that these issues were not identified before the article was published."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to"} +{"text": "The correct values should be for the fifth column and for the last one. In other words, the values from the fifth and last columns have been interchanged. The corrected In the original publication , there w"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The version of Figure 1 that appeared in the paper was incomplete. A complete and correct version of the the figure is available here:"} +{"text": "Neisseria Meningitidis is the greatest risk to young adults for fatal meningitis. It has been seen in other studies that smokers carry an increased amount of this bacteria and can be carriers for the infection. The aim of the study is to determine whether the smoking legislation brought into the UK has had an effect on the case numbers of meningococcal meningitis, as smoking in seen as a risk factor.Data was obtained from HPS and HPA to get national figures over a decade spanning the smoking ban legislation.Results show that there has not been a dramatic decline in cases of meningococcal meningitis since the introduction of the smoking ban.There should be continued surveillance in the future to see if a there is a long term trend with rates of meningococcocal meningitis cases."} +{"text": "Following the publication of this article, a number of concerns were brought to the attention of the Editors of PLoS ONE in relation to this research. In particular, the reliability of the data reported in Tables 1 and 2 has been questioned. The authors have indicated that they do not have access to the raw data on which the results are based, as a result, the authors retract the article given that it is currently not possible to verify the validity of the results.Details on the specific concerns raised on the article are outlined below:- The contents of the manuscript have been taken almost entirely from one of the chapters of the first author\u2019s PhD thesis, which was carried out under Dr Markus Noll\u2019s supervision at the University of Z\u00fcrich. However, the authors did not discuss the contents of the manuscript with him and he was not included as an author.- The references to Markus and Hans Noll under the Acknowledgements are inadequate as they were not shown a copy of the manuscript submitted for publication.- The work was carried out at the University of Z\u00fcrich; the funding information should have also acknowledged funding by Kanton Z\u00fcrich.- Work carried out by Noll\u2019s group in order to test the data reported in Tables 1 and 2 showed rescue efficiencies of survival and male fertility considerably lower than those reported in the article. The authors have indicated that they do not have access to the raw data on which the results are based, it is therefore currently not possible to verify the results or to carry out an adequate comparison of the data against those obtained by Noll\u2019s group.The authors would like to apologise to the readers and Dr Noll."} +{"text": "The version of Figure 1 that exists in the article is incorrect. The correct version can be found here:"} +{"text": "Due to an error in the production process, the version of Figure 2 that appeared in the article was incorrect. The correct version is available here:"} +{"text": "The following information was missing from the Funding section: The reported work was also supported in part by a research grant from the Natural Science Foundation of China (No. 81100309 to YB)."} +{"text": "The following was incorrectly appended to the Abstract, and should be read as the Acknowledgement Statement as is already indicated: \"The authors want to thank Jon Laurent and Kris McGary for some of the data used, and Li and Patra for making their code available. Most of Ambuj Tewari's contribution to this work happened while he was a postdoctoral fellow at the University of Texas at Austin.\""} +{"text": "On page 7 of the PDF there is a large section of text missing from the Discussion. The correct text can be seen in the online version of the manuscript."} +{"text": "This article was republished in order to correct an error in the Editor name."} +{"text": "We reported that the effect of vitamin C on asthma in Egyptian children was modified by age, exposure to dampness and the severity of asthma . After o"} +{"text": "In the Data and Methods section, there are errors in the first and second equations. Please view the correct equations here:"} +{"text": "The name of the seventh author is incorrect. The correct name is Anwar Anwar-Mohamed. The abbreviation of this name in the Author Contributions Statement is correct as it is."} +{"text": "Figure 15 is incorrect in the PDF. It is correct in the online version of the article."} +{"text": "Following the publication of this article, the editors were alerted to concerns over the accuracy and clarity of information reported regarding the source of the samples included in the study.The editors were contacted by representatives of the Borneo Orangutan Society who indicated that the samples included in this study were collected by the society for surveillance purposes as per the requirements under Indonesian law, and submitted to Airlangga University for routine tuberculosis tests. The Borneo Orangutan Society indicated that the samples originate from animals kept in rehabilitation camps and that they had no knowledge of the additional tests carried out for the purposes of this research.We have followed up with the authors in relation to these concerns and while we have received confirmation that the samples were collected for surveillance purposes, we have not received a satisfactory response to the request for specific details for the origin of each of the samples included in the analyses or the methodological steps involved in their collection.In the light of this, the editors are issuing this Expression of Concern to make readers aware of the concerns over the origin as well as the methodology followed for the collection of the samples tested in the study. The editors have also raised the concerns in relation to this matter to the attention of representatives of Airlangga University and the Indonesian government."} +{"text": "There is a grant number missing from the Funding Statement. The following is the missing information:This work was supported by Grant No. ZR2010HM046 from the Shandong Science and Technology Committee of China."} +{"text": "The abstract of the article cited consumption of uncooked poultry products as one of the most commonly identified factors associated with H5N1 virus infection. While this factor has been previously mentioned in the literature, it was not identified as such as part of the results of the systematic review reported in the article.Given that the consumption of uncooked poultry products was not identified as a risk factor associated with H5N1 virus infection as part of the Results reported in the article, the reference to this in the abstract may lead to confusion. The authors are therefore publishing this Correction in order to remove the statement related to consumption of uncooked poultry from the abstract."} +{"text": "There was an error in the name of the eighth author.The correct name of this author is: Jing Lu"} +{"text": "There was an error in the name of the second author. The correct name of this author is: Andreas Langousis."} +{"text": "The authors regret that in the production of The authors would like to apologise for any inconvenience this may have caused to the authors of this article and the readers of the journal."} +{"text": "The authors are sorry to report that the structure of rhizobitoxine in Figure 2 in their published paper was incoWe apologize for any inconvenience caused to the readers."} +{"text": "There was a error in the equal contributions designation and in the corresponding address of the second author in the online version of the article. Nico Posnien and Corinna Hopfen contributed equally to this work. The listed current address is for Corinna Hopfen. This information in the PDF version of the paper is correct."} +{"text": "After the article was published , we becaWe hope that you are able to make the necessary amendments to this error and apologize for any inconvenienced caused as the result of this misprint."} +{"text": "As a result of problems in the production process, there were errors in the version of Figure 2 that appears in the PDF version of the article. The version that appears in the online version of the article is correct."} +{"text": "There was an error in the name of the ninth author.The correct name of this author is: Ian McLennan"} +{"text": "There was an error in the first equation in the third paragraph of the Spread and Tracing on the IFTN section of Results. The correct equation can be viewed here:"} +{"text": "The core of the text as well as the legends remain the same as in our article since th"} +{"text": "Dear Editor,Mahboobi et al. should be commended for providing a clear and exhaustive review of the literature on the intriguing topic of the association of HCV infection with Lichen Planus . It is s"} +{"text": "After the publication of this work , we notiWe apologise to the readers and OncoGenex Technologies for this oversight and any negative effects that may have resulted from it."} +{"text": "After the publication of this article, concerns were raised about the inclusion of a figure which reported a map of the Nairobi CBD showing the location of the sex worker hot spots involved in the study and the number captured at each location during the enumeration.In light of the possible implications that the public availability of this information can have on the Nairobi sex workers, the authors have decided to withdraw this map from the publication. The article has therefore been republished without the original Figure 1. Any readers with an academic interest in the information originally displayed in the figure may contact the authors directly in relation to this information."} +{"text": "A reference is missing in our paper . Figure WBANs application in the medical field are composed of wearable and implantable sensors that can detect information from the human body and send it to a central unit as shown in"} +{"text": "I read with great interest the review by Falase and Ogah on cardiomyopathies and myocardial disorders in Africa.8The second issue relates to the following statement in the abstract and text of the review: \u2018there are no reports of \u2026 ion channelopathies in Africa\u2019. I would like to draw the authors to the discovery of impaired endocytosis of the ion channel TRPM4 as a cause of human progressive familial heart block type I in South Africans.The third issue is one of clarification. The authors refer to genotyping the \u2018Hb\u2019 gene in patients with cardiomyopathy. It is not clear what the \u2018Hb\u2019 gene is, or the rationale for postulating a linkage with cardiomyopathy. Information on the locus on the gene map and laboratory conditions used for typing the gene would assist other investigators in verifying the findings of the authors.The fourth issue from the review relates to the discussion of the classification of cardiomyopathies. The authors propose a new classification that is based on the proposal of the American Heart Association.I have found that the European Society of Cardiology classification lends itself well to the clinical evaluation of patients with unexplained heart failure in the African setting.Finally, the authors make a case for a new and unique classification of myocardial disorders for Africa. It is not clear why Africans should be an exception to other populations of the world. We have shown previously that while the burden of disease may be higher for certain forms of cardiomyopathy in Africa, the pathophysiological features of the cardiomyopathies are likely to be the same in all continental populations."} +{"text": "A previous version of the manuscript was mistakenly published. A note linking to a correct version of the article can be found on the article page. Text was removed from the Abstract. A sentence was removed from the first paragraph in the Results and three sentences were added to the fourth paragraph in the Results. Text was added to the second and fourth paragraphs in the Discussion and text was modified in the third paragraph in the Discussion. The text for the legend of Figure 3 was also modified. The figures themselves were published correctly."} +{"text": "Three of the authors were unaware that their names had been added to the author list. The three remaining authors were not involved with the treatment of the patient."} +{"text": "The quality of the version of Figure 6 that appears in the article does not allow for the reproduction of certain data.A correct version of the figure is available here:"} +{"text": "There was a formatting error in the last sentence of the first paragraph of the Haplotype Inference, LD Estimates and Variant Tagging section of Methods. The symbol that should appear in the parentheses can be viewed here:"} +{"text": "We thank the authors for their interest in our article and are interested to hear that our findings correlate well with that of their own experience. We did not intend to discount the effect of clinical judgement and indeed the study was not designed to assess this, as it did not include patients who never required CT, or those who had CTs but never required operative intervention.The accuracy of clinical judgement and the effects of CT on this have been well documented elsewhere."} +{"text": "As a result of errors in the production process, the version of Figure 6 that appeared in the article was incomplete. A correct version of the article is available here:"} +{"text": "There is an error in the first column of Additionally, there is an error in the title for"} +{"text": "Delivering the anvil of a circular stapling device into the pelvis during a laparoscopic anterior resection can be technically challenging. Once the anvil has been secured into the lumen of the proximal colon with a purse string suture, only the stem of the anvil can be used to manipulate it into the pelvis and the head of the stapling device. We report a simple and effective technique that assists in this task.The anvil is inserted into the proximal colonic lumen and secured with a purse string in the standard manner. After the knot has been tied on the purse string, a further loop is made on the suture and tied with a second knot . This loThis cost neutral and effective technique can be used to simplify the process of docking the anvil of the circular stapling device with the head of the gun during a laparoscopic left-sided colonic resection. It is particularly useful in a narrow pelvis."} +{"text": "The corresponding author requests the retraction of this article as the work was published without two key contributors. These contributors disagree with the publication of the article as it uses data that they had generated in part with the corresponding author but were not yet ready to publish themselves. The corresponding author sincerely apologises to the editor and readership for this misjudgement."} +{"text": "The authors informed the publisher that the term Democratic Republic of Congo was used instead of the correct name of the country \u2013 Republic of Congo in Figure 2, Tables 2 and 3 and the text. The author and the publisher apologise for this error. We have since corrected the online version of the article."} +{"text": "Reason for Erratum:Due to a typesetting error, a misalignment in Table The publisher apologizes for this error and the correct version of Table This error does not change the scientific conclusions of the article in any way."} +{"text": "In Figure The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in In addition, the legends of"} +{"text": "It has come to our attention that there is an error in one of the author names for this article . The aut"} +{"text": "Individuals with HIV in this study were 140 (and not 138 as previously reported), 135 cases with HIV were obtained from the MHBB (ant not 133 as reported). The percentage of men without HIV in the study was 63 (and not 73% as reported).The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "One of the funding sources was omitted from the Acknowledgments list. The corrected list is as follows. This research was supported by the National Institutes of Health (R01DC004263), the Army Research Office and the MSTP training grant .The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The publisher apologizes for the error.The Data Availability statement for this paper is incorrect. The correct statement is: All relevant data for the experiments described in the paper are available for download both at"} +{"text": "There are errors in the title and legend of Additionally, the following information is missing in the legend for There are two errors in the footnotes for Additionally, there is an error in the footnotes of Tables"} +{"text": "There is an error in the legend for There is an error in the image for"} +{"text": "We have become aware that the processing of image data in Figures On the basis of the original data obtained by SO, the figure was prepared. All authors approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After two years of study and conversation a group of 20 hydrocephalus investigators developed a consensus on a new classification of hydrocephalus based on point of obstruction. This new classification has proved useful in the diagnosis and treatment of patients with hydrocephalus of all types and is especially helpful in assessing the various treatment options for the individual patient.This is a retrospective review of a patient with a complex form of hydrocephalus related to a Dandy Walker Malformation who had had over 60 shunt revisions in the two years prior to first being seen at our insitution. She was evaluated as to potential points of obstruction and the best treatment for each point. The plan was to make certain that all compartments containing CSF were to be made to communicate with each other and that a maximum of one valve would be used if further treatment is needed.Using injections of Iohexal tracer for CT it was shown that there were very small lateral and third ventricles and obstruction to flow from through the aqueduct and from the cortical subarachnoid space into the encysted fourth ventricle. Treatment progressed in stages with fenestration of the cyst and replacing the shunt with a reservoir and \u201cButterfly needle.\u201d The lateral and third ventricle dilated and it was shown that now there was a fourth ventricle containing a floppy collapsed cyst within it. Following endoscopic third ventriculostomy she is now without a shunt and is back to school for the first time in 2 years. Follow up is 9 months.The vast majority of cases of hydrocephalus are due to distinct sites of obstruction to flow of CSF. Normal CSF dynamics demand that all CSF compartements communicate freely and that the intracranial pressures are normal. At this point if the ventricles are able to increase in size the patient is likely (>80%) to be able to be managed without a shunt with or without an endoscopic third ventriculostomy."} +{"text": "In Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the funding statement one source of funding was missing. This is now rectified as follows:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Reason for Erratum:Due to a technical error, the Supplementary Material for the article, containing the chemical structures was omitted from the published article. The publisher apologizes for this error and the correct Supplementary Material has been added to the original article.This error does not change the scientific conclusions of the article in any way."} +{"text": "Due to an error, there is an mistake in panel C of the original version of Figure The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is correctly included in full in this erratum."} +{"text": "Unfortunately, one of the affiliations included in the online published article is wrong. The complete and correct author's affiliation list is given here.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The total number of competencies mentioned in the Abstract and pages 4 and 5 of the paper are erroneously reported as 60. The actual number is 57. Apologies for the involuntary mistake and confusion created.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In their recent work, Ralser and colleagues (Keller Whether this was the case is not known at present, but these hypotheses are just a few of the many stimulating research avenues that will be spurred by this technically and conceptually stimulating work.The notion of the prebiotic Archean The author declares that he has no conflict of interest."} +{"text": "Frontiers in Pharmacology. The authors do not agree to the retraction or to the notice.The journal retracts the 11 June 2014 article cited above. Based on information discovered after publication and reported to Frontiers in November 2015, the article was examined, revealing that the complaint was valid and that the article should be retracted due to insufficient scientific quality. The retraction of the article was approved by the Field Chief Editor of"} +{"text": "Unfortunately, the original version of this article containeThe title has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "It has come to our attention that during the production of this article , the nam"} +{"text": "In the paper by Svoboda et al., a mistake was made in the Acknowledgment Section. The corrected Acknowledgments follow:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the third sentence of the second paragraph of the \u201cStatistical Analysis\u201d subsection of the Materials and Methods. The correct sentence is: The CI curves were estimated using the 1-Kaplan-Meier probability plots.There are a number of errors in the headings for Table 2. Please see the corrected There is an error in the legend for There is an error in the legend for"} +{"text": "There is an error in the legend for There is an error in the legend for"} +{"text": "The authors also wish to change the content of The authors wish to make two changes to their published paper . The worThe changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "Due to an oversight, in the original article Min Wu and Yuanyu Zhao were not included in the author list. They have now been added and the correct author list can be found above. We have also updated the Acknowledgements section to reflect the financial support received by these two authors.The correction does not affect the scientific validity of the results.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "It has come to our attention that there is an error in the methods section of this article . The sen"} +{"text": "Reason for Corrigendum:There was a mistake in the author's affiliation as published in the Opinion article. The correct affiliation is Department of Technology and Psychology and not Department of Technology and Technology as reported.The author apologizes for the mistake. This error does not change the content or opinions put forward in the opinion article as published.The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the author group affiliation. The correct sentence is: Membership of the COGNISEC Study Group is provided in the Acknowledgments."} +{"text": "In the HTML version of the manuscript there was an error in the title where the L of \u201clinc-RNA\u201d was replaced with an I. The first and last name of the corresponding author was also reversed. The pdf of the manuscript was unaffected. These errors are now corrected."} +{"text": "There are errors in the Funding section. The correct funding information is as follows: This project was supported by a grant from the Rheumatology Research Foundation."} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Reason for Corrigendum:x axis of Figure x axis only includes the range 20\u2013120\u2009ms. The new figure includes the appropriate axis values. The authors apologize for the mistake. This error does not change the scientific conclusions of the article in any way.There is a mistake in the values of the The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the third sentence of the second paragraph of the Discussion section. At the end of this sentence there should be a link to Reference 17 instead of reading (REF). The correct sentence is: Additional sequencing would be required to confirm whether other lineages or genotypes have been circulating in the Caribbean as has been the case in Brazil [17]."} +{"text": "The name of the second author should be read as Medicharla V. Jagannadham.The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in There is an error in the caption for There is an error in the caption for There is an error in the caption for"} +{"text": "There is an error in the Correction published on May 15, 2015. The corrected headings for There are a number of errors in the headings for"} +{"text": "Two additional papers that are featured in this Research Topic are published in Frontiers in Terrestrial Microbiology. Valentin et al. explore Both authors consulted on and drafted the commentary.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "It has been brought to the corresponding author\u2019s attention by the administration office that some of the authors present in this paper are contThe new version is published as ."} +{"text": "It has come to the publisher's attention that the original version of this article containe"} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "There are a number of errors in the axes labels for There is an error in the axis label for There is an error in the axis label for There is an error in the axis label for There are a number of errors in the axes labels for"} +{"text": "In the paper by Petrasek et al., a mistake was made in the Acknowledgments Section. The corrected Acknowledgments follow:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are errors in the presentation of There is an error in the equation in the Data section. There is an incorrect subscript denotation in the second line. Please view the complete, correct equation here:"} +{"text": "After publication of the original article , it was In addition to this error, it was noticed one of the references had been duplicated. Reference 23 and confThere were also edits made to the original article in the lA similar edit was also made to the last sentence of the \u2018Background\u2019 section in the original article . The sen"} +{"text": "Unfortunately, in the PDF of the original version of this article there waThe names have been also updated in the original article."} +{"text": "There are errors in the title for There is an error in the legend for There are errors in the title and the key for There are errors in the key for There are errors in the key for There is an error in the second sentence of the Discussion. The correct sentence is: We have demonstrated that, as a result of concussion, the brain has increased rCBF and consequently higher venous oxygenation."} +{"text": "In the XML version of the published article, the legend for"} +{"text": "Reason for Erratum:Due to a misunderstanding the Acknowledgment Section was missing from the published article. The publisher apologizes for this error and the original article has been updated.This error does not change the scientific conclusions of the article in any way."} +{"text": "Article was publThe Editorial Office takes full responsibility for this error. We apologize to the authors of the article and readers of the journal that this error was not fixed until now."} +{"text": "There is an error in the caption for There are errors in the caption for"} +{"text": "The publisher apologizes for the error.There is an error in the link displayed in the Data Availability statement. The correct link destination is"} +{"text": "Due to an error in the preparation of The authors would also like to provide a clarification in relation to The authors are supplying a corrected"} +{"text": "The authors wish to make the following corrections to this paper : Due to The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Figure The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the reference range of the first sentence of the Introduction in the XML version of the article. The sentence should read: Glial cells are proposed to be important players in seizure disorders because of their critical role in maintaining extracellular ionic homeostasis in the nervous system [1]-[5]."} +{"text": "Since tNilsson et al. discuss The series of articles included in the present collection is completed with a commentary by Khoury et al. on the pThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Children Editorial Office wishes to notify its readers of a correction in [The ction in . In prooThe The manuscript will be updated and the original will remain available on the article webpage. The authors would like to apologize for any inconvenience caused."} +{"text": "It has come to our attention that there is an error in one of the author names in this article . The aut"} +{"text": "In the original article, the caption of Figure 5 contained an error of acknowledgment for the figure source. It should be: (redrawn from von der Emde, The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "It has been brought to our attention that in Fig. two of the article , the imm"} +{"text": "The arrangement of the panels in Figure 4 of the article by Schulz et al. (2010) is incorrect. The order of the panels A and B in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was an error in the final printing of one of the author\u2019s names in the original article . It was"} +{"text": "Due to an error during production, the legend of We apologize for any inconvenience caused to readers or authors by these changes. The article will be updated and the original will remain available on the article webpage."} +{"text": "The authors are issuing a correction for the unintended oversight in attribution to this work. To that"} +{"text": "Early we described a local internal lateral fixation (LILF) of a dura mater spinalis to the wall of the vertebral channel as the main reason of the serious idiopathic scoliosis.There are a postmortal investigations of the serious scoliosis with a LILF of duramater. Early it was considered by other author that this a secondary phenomenon as a consequence of the vertebras edges pressure in the vertebral channel towards the dura mater. by overc"} +{"text": "Despite the fact that the population of is rapidly aging , Award Number R01AG044335.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "On the original article the acknowledgment section was missing a funding source. The correct and updated acknowledgments are below.The authors declare that the research was conducted in the absence of any commercial orfinancial relationships that could be construed as a potential conflict of interest."} +{"text": "Heymann .A correction is made to the article by et al. Heymann is corrected.The name of one of the authors in the article by"} +{"text": "The following information is missing from the Competing interests section: Jean Peccoud holds a financial interest in GenoCAD and serves as the company\u2019s CEO. This affiliation does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.GenoCAD did not provide any funding for this study and was not involved in the design of the research, the collection of data, or the preparation of the manuscript."} +{"text": "Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to correct some errors with the data that came to light after the publication of the article:Due to an error, the original There was a discrepancy in the handling of data for Supplemental The authors would like to apologize for these errors and confirm that these corrections do not affect the conclusions presented in the article.S4 Table(XLSX)Click here for additional data file."} +{"text": "The hippocampal formation contains the head direction cells, the grid cells and the place cells which work as an internal GPS for the brain. The head directions cells can sense the direction in which the animal is moving, based on which the entorhinal grid cells fire at regular intervals as the animal is at the corners of an equilateral triangle and the hippocampal place cells fire whe"} +{"text": "In the version of this article initially published online, there are two typos in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "We have recently been made aware by a reader of a typo in Equation (4a) of our recent paper . The equWe would like to make the following corrections:This sign correction does not affect the modeling work presented in the paper, since the mistake appears only in the text, and the correct sign was used in the model. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Concerns were raised by a reader about Fig PLOS Staff Editors contacted the authors for a response to these concerns and to request the original images for these figures. The authors acknowledged that some of the panels were derived from the same image, which they suggested was caused by errors when cropping and cutting the original images.The authors have declared that the figure errors have no effect on the results and conclusions of the study. They have provided the journal office with the original and corrected images for Figs Please view the corrected images for Figs S1 File(ZIP)Click here for additional data file."} +{"text": "We have noticed that during the revision process of the original manuscript a modification in the analysis script to enable the parallel processing of more data sets led to incorrect indices for the selection of active dipoles. This mistake in the analysis pipeline affected the results of SFPC, i.e., Figure 5 and the part of Table We corrected this mistake in the analysis script and reanalyzed the 5 Subjects. While this affected the individual frequency power time courses, it did not result in a more stable correlation with the RSN timelines. The corrected Figure 5 of this erratum depicts the corrected rank graphs for SFPC, which show only minor differences to the erroneous graphs in the original Figure 5 of the published manuscript. This reflects a similar inter subject and temporal variance independent of the change in dipole location.We also noted a lapse in the part of the original Table It is important to note that the corrected results did not impact on our original conclusions of the published manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "RABfarms, were there was an increase in MRSA prevalence from the beginning of the cycle to week 12 .There is an error in the fourth sentence of the \u201cMRSA prevalence in the human study population and effect of study arms\u201d section of the Results. The correct sentence is: The same was true for the second cycle except for There are errors in the captions for Figs"} +{"text": "In In There is an error in the first sentence of the \u201cQuestionnaires\u201d subsection of the Results. The correct sentence is: The BBQ Regularity item increased significantly over the months covered by the study .There is an error in the first sentence of the fifth paragraph of the Discussion. The correct sentence is: A steady CCR was established during the first year of life as well as a significant increase in regularity (as described in the BBQ Regularity item) developed ."} +{"text": "We noticed that some symbols were lacking in Table 5 and some of the Plant Family names were not currently accepted.We hereby present the Tables Apologies for any inconvenience this may have caused.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Due to a typesetting error, the labelling was changed and the figures in this article were pre"} +{"text": "AmendmentCurrent address of the author is Newomics Inc., Emeryville, CA.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The source of the funding of this work disclosed on the published paper was incoAcknowledgments: This work was funded by Suranaree University of Technology\u2019s research and development fund. The authors would like to apologize for any inconvenience this may have caused to the readers."} +{"text": "In the version of this article initially published, there was an error in This error has been corrected in the PDF version of the article."} +{"text": "The x axis in Figure DW is affiliated with NeuroBehavioral Systems, Inc., the developers of Presentation software used to create these experiments. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are multiple errors in the equations in the last sentence of the third paragraph of the \u201cStatistics\u201d subsection of the Materials and Methods. The correct equations are:There is an error in"} +{"text": "It has come to our attention that during the production of this article , the nam"} +{"text": "Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Grant information was missing on the original publication. The updated acknowledgment section is provided below.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the caption for There is an error in the caption for"} +{"text": "The publisher apologizes for the error.In the Abstract, the link to the trial registration is incorrect. The correct link is:"} +{"text": "Members of the 2015 ICEID Scientific Committee and a list of peer reviewers are provided at the end of the PDF document.Emerging Infectious Diseases is providing access to these abstracts on behalf of the ICEID 2015 program committee (Emerging Infectious Diseases has not edited or proofread these materials and is not responsible for inaccuracies or omissions. All information is subject to change. Comments and corrections should be brought to the attention of the authors."} +{"text": "Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Nutrients Editorial Office wishes to make the following correction to this paper. The correct Due to mistake during the conversion process, the We would like to apologize for any inconvenience caused to the readers by this mistake."} +{"text": "It has come to our attention that there is an error in one of the author names for this article . The nam"} +{"text": "It has come to our attention that there is an error in the author list of this article . In the"} +{"text": "The authors are retracting this article because The authors wish to emphasize that the in vitro and in vivo methods and results presented in this article were val"} +{"text": "Reason for Corrigendum:\u22121 DW\u201d as in the new version of Figure There was a mistake in the unit of the y-axis legend of Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After publication of the original article , it cameThe image duplication occurred when the images were used as a placeholder for forthcoming data. The choice of image was independent of data analysis and thus does not change the results of this study. The correct image for Fig.\u00a0The authors sincerely apologize for the inadvertent error and the inconvenience to the journal and the readers."} +{"text": "In the original article, the title of the article in the Supplementary Material was wrong. The correct Supplementary Material appears below. This mistake does not change the scientific conclusions of the article in any way.The author apologizes for this error.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors and the journal wish to retract the 19 October 2015 article cited above. The authors requested the retraction of this article in November 2015 as data was included in this article which had been released without the permission of all collaborators involved in the research project."} +{"text": "Unfortunately, the original version of this article containeWe would like to apologize for this error and for any inconvenience this may have caused."} +{"text": "The PFCThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Figure The original article was updated.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After publication of this article , the autThe correct presentations of the authors\u2019 names are included in the author list of this erratum and have also been updated in the original article ."} +{"text": "The authors wish to make the following correction to this paper . Due to We apologize for any inconvenience caused to the readers."} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "The authors and the journal wish to retract the 6 November 2012 article cited above.Based on information discovered after publication and reported to the journal in November 2014, this article was found to contain sections that were taken verbatim from other sources without giving proper reference to the source and without identifying the citation as a word-by-word citation from that source. In addition, credit was not given to all authors of the research reported in the article and copyright permissions were not obtained for the use of Figure 1. The authors agree with the retraction of the article and apologize to the readers, reviewers and editors of Frontiers in Microbiology.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear editors,We thank the authors of the Letter to the Editors for their thoughtful comments on our systematic review . They emThe authors refer to four papers not included in the review \u20135. ThreeWe would like to reiterate the point made by our colleagues in their letter; it is time for the research on pain in HIV/AIDS to move beyond identifying and describing the problem of pain in people living with HIV/AIDS and on to developing and testing interventions which will improve pain assessment and management."} +{"text": "The authors would like to acknowledge that the article contains overlap in text with that from our previous publication [1] and fragments in the text that overlap word-for-word with text from our previous publication [2] and a publication in Environ Toxicol Pharmacol [3] .The authors apologize for the overlap, for omitting to cite the publication [2] and for not properly quoting the text from . The overlap in text relates to some of the information described in the Introduction section and to the description of the methodology under the Materials and Methods section.However, it should be noted that the identified issues have no bearing on the results and conclusions of the study."} +{"text": "The Editorial Board has been informed by the authors of \u201cCo-receptor CD8-mediated modulation of T-cell receptor functional sensitivity and epitope recognition degeneracy\u201d that the parameter values as reported in the legends are mutually inconsistent and therefore the results of the simulations have to be reconfirmed. This is to notify readers that the data as published in the original article are not validated and that the authors have stated to the Editorial Board that a Corrigendum is in preparation."} +{"text": "There is an error in There is a typographical error in the last sentence of the paragraph following"} +{"text": "This study was supported by a grant to Lauren Stewart from the Economic and Social Research council .The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Unfortunately, the original version of this article containeThe name has been updated in the original article and is also correctly included in full in this erratum."} +{"text": "In Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Estimating the synaptic conductances impinging on a single neuron directly from its membrane potential is one of the open problems to be solved in order to understand the flow of information in the brain. Despite the existence of some computational strategies that give circumstantial solutions (-3 for in"} +{"text": "There is an error in The equation numbering is missing in the published article. Please see the equations and their associated numbers here."} +{"text": "To the EditorWith reference to the interesting paper by Algahtani et al,Reply from the AuthorNo reply was received from the author"} +{"text": "There was an error in the nomenclature in original Figure 1. Members of the genus Ruminococcus belong to the phylum Firmicutes, not Proteobacteria. This has now been corrected in this revised figure.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After publication of this article , it was We regret any inconvenience that this inaccuracy in the figures in the original manuscript might have caused."} +{"text": "There is an error in the last sentence of the penultimate paragraph of the Introduction. The correct sentence is: Further analysis of the enhancement of metastases in mCC11 cells revealed that this occurred in only one of three immunocompromised mouse strains, arguing that this is not a tumor cell intrinsic response."} +{"text": "The name should be indexed as Moita LF and not Ferreira Moita L. The publisher apologizes for the error.There is an error in the XML that is causing the 8"} +{"text": "The authors would like to add the following correction to the Opinion article to now include the acknowledgment of funding for their research.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "We wish to make the following correction to the published paper . The corWe apologize to the authors of the article and readers of the journal for any inconvenience."} +{"text": "There are a number of errors in the figure legends for this article. In the legends for"} +{"text": "After publication of the original article , it was The correct linking for the Additional Files is included in this erratum."} +{"text": "I would like to share my experience from nearly a decade of civil war between the Maoist rebels and the Royal Nepalese Army in Nepal in reference to the article by Zwi"} +{"text": "Might explanations for this be that there were no attempts to engage patients or carers who may not have been willing or able to be engaged or that the bureaucratic pressure and time involved in the recording process were experienced as barriers?"} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Note that all the authors agree with the decision to retract this article. The Editor and the authors regret any inconvenience that this retraction will cause to the readership of the Journal.The Editor of"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , it was The publisher apologises to the authors and readers for the inconvenience caused by the error."} +{"text": "The authors regret that the image used for Fig. 1e in the original manuscript was from an incorrect sample.The correct image is given here.The authors state that the findings and overall conclusions presented in the original article are unaffected by this change.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "In the published article, there was an error in the caption of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , it was The publisher apologises to the authors and readers for the inconvenience caused by the error."} +{"text": "There is a mistake in the top cells of Table 2 in the original publication of the article. The top cells should be shifted one column to the right to make it inline with the corresponding data. The correct Table The original article has been corrected."} +{"text": "In the published article, there was an error in In the published article, there was an error in In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "What is the European Public Health Week? What's it's impact and why do you want to be part of it?"} +{"text": "In the initially published version of our article, we recently realized that there are errors in several figures and Table 2 due to misplace of images and data. The corrections are provided below.Finally, the author list in the paper should be updated as above in this erratum.The correction does not change the overall conclusions of this paper. We apologize for the error and for any inconvenience that may cause to the readers and the editors of this journal."} +{"text": "The authors wish to make the following change to their paper . We realThe authors apologize for any inconvenience caused and state that the change does not affect the results of the study and the conclusions drawn from it. The original publication has also been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure 7 should be changed from: The authors wish to make the following changes to their paper . Due to to: The authors would like to apologize for any inconvenience caused to the readers by these changes. The changes do not affect the scientific results. The original publication has also been updated."} +{"text": "We did not catch this unfortunate error during the production process, and the manuscript published with the error included. We have now corrected the spelling, and the correct author list appears here and in the online version of our article. We apologize for the oversight."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The revised version of Experimental and Therapeutic Medicine for granting them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused.Note that this error did not have a major impact on either the overall results or on the conclusions reported in this study. The authors regret the errors that were made during the compilation of the data into"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure 3, and In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Had we been aware of this important prior work,we certainly would have referenced it. For this reason we are nowpublishing this minor correction so the prior article is properlycited and the two articles in the record (and on indexing services)are more transparent to the community.Near the time of the submissionof our now published manuscript"} +{"text": "The given name and family name of all the authors were reversed in the original version of the publication. It has been corrected with this erratum."} +{"text": "Following publication of the original article , it was The figure has been corrected in the published article and the correct figure is shown in this correction. This correction does not affect the results or conclusion of the article.The authors apologize for any inconvenience caused."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret the inclusion of an error in the title of their correspondence.When originally published, the title for this paper had the year of the article it responds to incorrectly stated as 2022. The correct year for this article should have been 2021.This has now been corrected."} +{"text": "In this article the statement in the Funding information section was incorrectly given as \u2018SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from AstraZeneca\u2019 and should have read \u2018SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from Merck\u2019."} +{"text": "The future of psychiatry as a discipline can best be grasped on the basis of an examination of the development of psychiatry over the past century in the light of current options for its functioning. Such an examination demonstrates that psychiatrists will have to expand their field of work to include the management of comorbidity of mental and physical disorders and public health approaches to the primary prevention of mental and other brain disorders. Their engagement in research will have to become restricted to psychopathology and participation in the formulation of hypotheses which will be tested in laboratory and field work;; and their involvement in teaching about mental health and illness will have to undergo a fundamental change in terms of content, methods and evaluation of effects of education which they will organize. The presentation will focus on the future tasks of psychiatrists in these areasNo significant relationships."} +{"text": "From the perspective of international economic governance, other than casting aspersions on the judgement of those that negotiated previous multilateral trade accords and the accession of China to the World Trade Organization, the deglobalisation narrative is silent on how to reform that organisation \u2014 or what to salvage from existing global trade rules."} +{"text": "The PDF version of this article reflected an older version of the article with an incorrect URL for reference 17, while the HTML version was correct. The PDF has been updated to the correct version."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The numbers 432 and 433 found in the 6th paragraph of the Discussion section is not included in this paper and should be removed.The Original article has been corrected."} +{"text": "In the original article, there were mistakes in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there is an error in .In the published article, there is an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the article titled \u201cSimulation of the Final Size of the Evolution Curve of Coronavirus Epidemic in Morocco using the SIR Model\u201d , the codIt is also noted that the use of a simple SIR model to predict the development of COVID-19 in its early stage was limited and did not account for parameters such as containment measures."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , the autThe problem is that 2 sequences of the primer list in Table 1 were wrong. In red are the ones that should be changed. The corrected version of Table"} +{"text": "In the published article, there was an error in The corrected In the published article, there was an error in 2O2 concentration under eLOS oxygen scavenging appear below.The corrected Error in Table carried over to the index figure.In the published article, there was an error in Index figure as published. This arose as a carry-over of the error in the formatting of the table that the publishers used as index figure A corrected index figure appears below corresponding to The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, an author name was incorrectly written as Trevaksis. The correct spelling is Trevaskis.main heading and in the citation information on page 1. It is also incorrect in the Copyright statement.Note this error is repeated in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :In the original publication, there was a mistake in"} +{"text": "In this first presentation of the workshop, Jon Txarramendieta, the Project Manager at the Coordination team of JADECARE will present the Joint Action and the challenges in transferring the good practices to the heterogeneous context of the Next Adopters. It will give context to the workshop and introduce good practices that are transferred into action."} +{"text": "Following publication of the original article , it was The correct name is given in the authorship panel of this correction, and the original article has been"} +{"text": "The authors would like to make corrections to the reference citations in the original article . The ordThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "The authors wish to make the following corrections to this paper : In the The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original article has been updated."} +{"text": "This article has been corrected at the request of the authors due to an error in the author order when originally published. The authors deeply regret that this error was not identified and corrected prior to publication. The correct author order is now shown."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : in the The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The first engagement in research in your career This presentation will argue that in addition to considering the scientific interest of a topic presented for research it is important to consider other criteria before engaging in a study. These include the place of the study, the team which will be engaged in the work, the ownership of the data which will be produced, the duration of the study and other matters. The presentation will also discuss the amount of time that should be given to scientific research early in one\u2019s career and the nature of the gain that engagement in research can offer for one\u2019s development and career.No significant relationships."} +{"text": "After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the data shown in one of the panels belonging to the flow cytometric experiments shown in Fig. 5C were strikingly similar to data appearing in different form in another article published by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to"} +{"text": "To evaluate whether the practice in the generic CAMHS team Winsford is in line with the guidelines recommended by NICE in identification and management of depression in CYP. To formulate an action plan that might be needed for the recommendations that are not met currently.Review of online case notes, protocols, pathway descriptions, screening forms and proformasRandom review of the last 12 months of practice with random five cases studied per case manager regarding identification and management of depression in the children and young people at the center. To assess this, a proforma will be prepared from the guidelines relevant to the team members. This proforma will be sent to all the clinical workers of the team who will be required to fill it and return it to the lead author.The population to be included will be all secondary school aged children residing in West Cheshire who are referred to and assessed and managed by the CAMHS community center, WinsfordTo collect the relevant information about the identification and management of depression in young people in our community center by following methods:I am working on this audit currently and will be obtaining the results in two months\u2019 time and hopefully will be able to submit the audit poster well before the International Congress.This audit will help the team to assess how diligently they are following the recommended NICE guidelines for the identification and management of depression in children and young people and to make appropriate changes in the process to meet the guidelines that are not currently met."} +{"text": "The authors regret their oversight in allowing these errors to be included in the paper, and also apologize to the readership for any inconvenience caused.The revised versions of"} +{"text": "Due to a mistake on the publisher\u2019s part, this article was originally published as a Systematic Review instead of Original Research.The publisher apologizes for this error and states that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Bioscience Reports at the request of several listed co-authors who claim to have had no involvement in the paper and that they were unaware of its submission and publication. The corresponding author has been contacted with regards to the retraction and has not responded to the Journal's queries or the concerns raised. Several listed co-authors wish to retract the article and the Editorial Board agree with the Retraction.This article is being retracted from"} +{"text": "This was due to the new LTCI applications that were not reflected in the LTCI system database at the time of reporting. Table In the original publication of this article,"} +{"text": "Figure 5B were accidentally repeated in In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Graphical Abstract as published. The Graphical Abstract incorrectly contained the text of the full abstract. The corrected Graphical Abstract appears below.In the original article, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the legends for Results part.In the published article, there was also an error with the figure citations. The figure citations in the text were not listed in sequential order in the Corrections have been made through out the article to correct the figure citations.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to apologize for any inconvenience caused to readers by this correction. Replacing this figure will not affect the results or conclusions of the paper. The manuscript will be updated and the original will remain online on the article webpage, with reference to this correction.After careful examination, we found that the structures of compo"} +{"text": "ChemComm paper.1 Although the ChemComm article was cited as ref. 15b, and here as ref. The authors regret that it was not clear in the original article that part of the graphical abstract image had been reproduced from the graphical abstract of an earlier The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Error in Figure/TableIn the published article, there was an error in In the published article, there was an error in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected figure and its caption appear below.In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors of the review discuss some of the findings by Singh et al. in the text and make reference to the work in Table 1 and Figure 2. Despite the retraction of this paper from the literature, the Editors at Immunotherapy Advances agree with Eberl et al. that there is a large body of complementary evidence in the literature demonstrating that the MEP pathway is an attractive target for the development of novel antibiotics and that manipulation of the MEP pathway has a direct effect on anti-microbial \u03b3\u03b4 T cell responses. As such we are confident that this retraction does not affect the validity of their article.We would like to alert readers to the recent retraction of one of the papers (Singh"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We wish to provide a correction of the colour representation of Fig.\u00a02 in order to harmonise the colours representing the Psilocybin and the Placebo condition with the corresponding figure caption and with the colour codes from all other figures across the manuscript. Fig.\u00a02 now depicts the Psilocybin condition in blue and the Placebo condition in yellow. The error occurred as a result of an oversight. This change does not affect the results presented in the paper and the figure legend remains unchanged."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in There was also an error in the caption for The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the article , the autThe affiliation has now been corrected in the original article and the updated affiliation can be seen in this correction."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "All the authors agree to the publication of this corrigendum, and are grateful to the Editor of"} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make a change to the published paper . In the The authors apologize for any inconvenience caused, and the change does not affect the scientific results. The manuscript will be updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "During the course of a review of our publication, we found two errors in All co-authors agree with the content of this correction and we would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the article XML that causes the PubMed citation to be indexed incorrectly. The publisher apologizes for the error."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Bioscience Reports at the request of several listed co-authors who claim to have had no involvement in the paper and that they were unaware of its submission and publication. The corresponding author has been contacted with regards to the retraction and has not responded to the Journal's queries or the concerns raised. Several listed co-authors wish to retract the article and the Editorial Board agree with the Retraction.This article is being retracted from"} +{"text": "This is due to the similar naming of the two images. The correct In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret that there was an error in one of the acknowledgements in the original article. The correct funding information for the National Basic Research Program of China is grant number 2016YFA0200800. Wenjie Liang\u2019s name was also spelled incorrectly in the original article. The correct author names are as presented above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "The authors apologize for this error.The original version is also corrected and can be found on the below link:"} +{"text": "In the published article, there were some errors in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article has been corrected with the consent of the authors to replace the term \"red man syndrome\" with \"vancomycin flushing syndrome\". In recent years, the term \"red man syndrome\" has fallen out of favor as it is now widely considered to be racist . The editorial office was alerted to this issue by a concerned reader, who we graciously thank for the insight. The authors are in full agreement regarding this change and together with the editorial office regret any harm caused by the use of the word."} +{"text": "The authors wish to make the following corrections to this paper :There are mistakes regarding the possibility for growth on several substrates shown in The correct version is as follows:The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "In the original article, there was an error in There was also an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We acknowledge the important points raised by the authors of the letter written With respect to the empirical implications raised in the letter , the BabWe also want to take the opportunity to clarify the distinction between \u201cincreased brain development\u201d as posited in the letter and our"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Due to a production error at the previous publisher, the The correct version of the The original version of this article has not been updated."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the Supplementary Tables file as published. An incorrect version of the Supplementary Tables file was uploaded, resulting in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Hence, the tests of these compounds were repeated twice again to confirm these results. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was a writing mistake in the schematic diagram of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to this paper . Due to with"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original version of our article, there was an error in Fig."} +{"text": "In the original article, there was a mistake in \u201c The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original publication , there wThe categories in the bar charts in In the original publication, there was a formatting error in The relevant section of the corrected The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there were two errors in The authors apologize for these errors and states that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret their oversight in allowing this error to be included in the published paper, and apologize to the readership for any inconvenience caused.The revised version of"} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original publication of this article the issue details of the references were not available. The article has been updated to correct this."} +{"text": "All the authors agree to the publication of this Corrigendum, are grateful to the Editor of"} +{"text": "The original version of our paper contained an error. In Figure All authors agree to the erratum and confirm that the corrections made in this erratum do not affect the original conclusions. The authors apologize for any inconvenience that the errors may have caused."} +{"text": "The authors wish to make the following correction to this paper :In the original publication, there was a mistake in The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "We thank Tsai and Liu for theiTo say that the study should be more quantitative negates that prospective sleep logging is both quantitative and the consensus tool for the field . What maThis seems a pertinent time to remind the authors of the letter that the"} +{"text": "In the published article, there was an error in The corrected Table and correct format appear below.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in In the original article, there was an error in the caption for The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "All the named authors agree to the publication of this Corrigendum, and apologize to the readership for any inconvenience caused.The authors have reassembled"} +{"text": "In the published article, there was an error in the legend for The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret that some of the affiliation details were incorrect in the original article. The address provided in the footnote for the first author in the original article should actually be the first author\u2019s current address (listed correctly here as affiliation a). The footnote for the second author in the original article should also have indicated that the address in the footnote is her current address .The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "This means the type 2 error in In the published article, there was an error in In the published article the same error was present in the The authors apologize for these errors and state that they does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected version of In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Due to a production error, there are two errors in the first column of The publisher apologizes for this mistake. The original version of this article has been updated."} +{"text": "In the original article, an incorrect representative image of immunofluorescent staining for cardiac fibroblasts was contained in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused.Given the multiple instances of overlapping data panels that have been identified in the compilation of the figures in this article, the Editor of"} +{"text": "In the original article, there was a mistake in \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The red arrows in the figure legends of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in The authors apologize for this error and state that this does not change the scientific conclusions of the manuscript in any way."} +{"text": "The Editors have chosen to retract this article on the grounds that there were significant procedural mistakes in the original paper, and a replacement paper is to be written. The errors are explained in detail in letters published in the journal."} +{"text": "There is an error in the special author designations; the publisher apologizes for the error. The correct designation is: \u2021 ME and CC are joint first authors on this work."} +{"text": "One of the responsibilities of academic publishers is to ensure that the publication record is maintained accurately. Therefore, Portland Press would like to inform the reader of the following.International Journal of Pharmaceutical Science Invention which reproduces significant content from this article without citation or attribution. We have attempted to contact the Editorial Office of the journal, the Editor-in-Chief and members of the Editorial Board and the Publisher in order to resolve this issue but despite repeated attempts no response has been received.We have been made aware of an article published in the We would like to inform the readers that we are aware that there is another version of the article available online and reassure you that this paper is the original and correct version of record."} +{"text": "Regarding the figure, the authors would like to highlight to the reader that the N values for hepcidin in Fig."} +{"text": "In the original article, there was an error. We neglected to state that the authors Qiankun Cai and Yuyou Zhu contributed equally to this work.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the initial article, the data in the"} +{"text": "In the original article, there were mistakes in the legends for In the first two sentences of the legend to The axis labels in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make a correction to their published paper .There was a mistake in the original version of the article in Figures 1 and 2. We found that Figures 1 and 2 were misplaced in the article.They should be replaced with the following The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "They also wish to emphasize that the errors made during the compilation of the figures did not substantially alter any of the major conclusions reported in the study, and apologize to the readership for any inconvenience caused.The corrected versions of"} +{"text": "This article was published in Psychological Medicine with an error in the author's affiliations. This has now been corrected online and in the article.The authors apologise for this error."} +{"text": "Following publication of the original article 1], it was reported that the names of all authors were published with their given name and family name in reverse order. The correct authorship list is given in this Correction and the original article [, it was"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following erratum to this paper :The addition of an author Ina L. Smith due to an omission.The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused."} +{"text": "After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in the legend for all of the figures as published. The source of the pictures cited in the article were not included. The correct legends appear below.The sources for the figures have been added to the reference list, and the reference numbering has been updated to accommodate this. The new references are appear below.The authors apologize for this error and state that authorization has been obtained from the author of each picture, and this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Taking everything into consideration, the Editor has decided that the article should be retracted from the publication due to a lack of confidence in the data presented in this article. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not received any reply. The Editor regrets any inconvenience that the retraction of the paper will cause."} +{"text": "Figure 3. The corrected In the original article, there was a mistake during production in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "All the authors agree to the publication of this corrigendum, and apologize to the readership for any inconvenience caused.The authors have re-examined their raw data and identified the data that should have been included in this figure. The revised version of"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , the autAuthors would like to confirm that this correction does not impact the conclusions of the study."} +{"text": "In the original article, there was a mistake in the artwork for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The name as it should have appeared in the author list is featured above.The authors regret that this error was not corrected prior to the publication of the above article, and apologize to the author concerned and to the readership for any inconvenience caused."} +{"text": "We are sorry to report that some images in to:This change has no impact on the caption of"} +{"text": "Error in FigureThe original image of the control group was incorrect. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This article was published in Psychological Medicine with an error in the name of the author Thomas Ward. This has now been corrected online and in the article.The authors apologise for this error."} +{"text": "The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already appeared in different form in another article prior to its submission to"} +{"text": "In the original article, there was a mistake in The author apologizes for this error and states that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure 4P as published. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way."} +{"text": "The authors wish to make the following correction to Figure 1 D in this paper [The authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "In the current version of the Table S13, we have listed the correct values. The correction of this error does not affect any of the reported results or conclusions of the paper but nevertheless should be stated correctly. The authors sincerely apologize to the readers for this unintended lack of thoroughness and any confusion that may have resulted from that."} +{"text": "In the original article, there was a mistake in In the original article, there was a mistake in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the article, the authors flagged that the article had published with incorrect affiliation details in the author list.The article has since been corrected and the updated author list can be found in this correction."} +{"text": "The published article has beenAdhering to our complaints procedure, an investigation was conducted and the article is therefore retracted.This retraction was approved by the Editor in Chief of the journal.The authors agreed to this retraction."} +{"text": "It was also drawn to the attention of the Office that certain of the tumor images shown in Fig. 6A were strikingly similar to data appearing in different form in other articles by different authors. Considering all these points, the Editor of The authors all agree with the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused."} +{"text": "In the original article , it was The authors apologize for this error and would like to reiterate that the scientific conclusions are unaffected."} +{"text": "The authors wish to make the following correction to their paper . In the The authors would like to apologize for any inconvenience to the readers caused by these errors."} +{"text": "Following the publication of the original article , the autThe new corresponding author Benjamin Terrier is shown in the authorship of this Correction as well as in that of the original article,\u00a0that has now been updated."} +{"text": "This article was published in Psychological Medicine with errors in the names of authors in a couple of references. This has now been updated and the correct names used.The authors apologise for this error."} +{"text": "In the original article, there was a mistake in \u201cThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , the autAll the changes that were requested are implemented in this correction and the original article has been"} +{"text": "Due to a clerical error, the values for the amount of technology use for business/school motives before the lockdown were reported incorrectly in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Conflict of Interest statement was inadvertently incomplete. The statement should include:In the original article, the \u201cSQ is a founder and shareholder of Mirvie, and Stanford University and the Chan Zuckerberg Biohub have filed patents based on the work of SQ and MM on the use of cfRNA in maternal and fetal health.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure 6. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the sixth sentence of the first paragraph of the Introduction which should not include reference to Intellia Therapeutics. The correct sentence is: These promising targeted therapies are the focus of synthetic biology companies such as Locus Biosciences and Eligo Bioscience, to name a few."} +{"text": "Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused."} +{"text": "The authors regret to declare that a figure that appears in the published article is not the correct one and may result to misunderstanding . The correct version of Fig. 8 is attached in this corrigendum. The authors would like to apologise for any inconvenience caused."} +{"text": "In the original article, there were mistakes in The authors deeply apologize for these errors and state that these corrections do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Error in FigureIn the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected Table 2 appears below.In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original publication, one of the grant numbers was published incorrectly in the Funding section. This has now been corrected in both the online PDF and HTML versions of this article. The authors apologise for this error."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Funding statement. The correct Funding statement appears below.There is an error in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Due to a production error, there was a mistake in The corrected The original version of this article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, the image of Bax in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The publisher regrets that the affiliations for the authors in this article were incorrect at the time the article was published. They are correct as presented within this erratum.The publisher would like to apologise for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The original version of the article unfortunThe other data and the conclusion in the publication are real and reliable.It has been corrected in this correction.The correct version of Fig."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the article by Reynolds et al.The article was developed from earlier versions that appeared in the following blogs:"} +{"text": "The authors would like to correct an error in the name of the condition in the recently published paper . The ter"} +{"text": "In the original article, the name of a company that did not formally collaborate with the authors of this study has been removed from the acknowledgements and supplementary materials to clear up misinterpretations.The correct acknowledgement and the supplementary information are provided in this article.The original article has been corrected.Supplementary file1 (PDF 772 kb)Below is the link to the electronic supplementary material."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article , there wThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to the affiliation and acknowledgments part . The affThe authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in the Figures as published. We accidentally deleted an important figure during the revision and resubmission process and did not catch this issue when proofreading. The correct The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the number labeling for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The published version of our article containsIn addition, structures that were shown in Figure We would like to thank the reader who brought the errors to our attention and apologize for any confusion that they might have caused."} +{"text": "To understand the possible trajectory of inflation in 2022 and beyond, it is helpful to understand why the United States and Europe had so much inflation in 2021."} +{"text": "The authors have requested that the following changes be made to their paper . Due to"} +{"text": "Supplementary Material appear below.In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , it was The table has since been corrected and the updated table is provided in this correction for reference.The authors apologize for any inconvenience caused."} +{"text": "Reviewers contribute greatly to shaping the quality of manuscripts published in our journal. Our reviewers give of their time and expertise to the service of science. We recognise those who reviewed for us in 2020. We hope that many more will respond to our invitation in the coming years."} +{"text": "Natural Science Foundation of China, 81802507.In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to"} +{"text": "The authors also requested either a corrigendum or a retraction of this paper on account of problems that has been identified with the antibodies used for the western blotting experiments. Upon consulting the authors, they agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already appeared in another article prior to its submission to"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "They also apologize to the readership for any inconvenience caused.The authors have examined their original data, and have been able to identify the GAPDH bands that should have been included in this figure. The corrected version of"} +{"text": "To the Editor,Thank you for providing us the opportunity to respond to the letter to the editor by Bo-Wen Zheng et al. We thank them for their interest in our study . The mai"} +{"text": "In thismponents and Subrmponents have assin vitro . In addiin vitro suggestein vitro recentlyMKH conceptualized the opinion and wrote the manuscript. The author also approved the final version of the submitted manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the published article, there was a mistake in the order of the listed authors. The correct authors list appears above.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : In the The correct version of Figure 2 is as follows:The correct version of Figure 4 is as follows:We stress that these errors were purely due to human error and oversight; the corrections made do not affect or change the written portion of the figure legend, the interpretation of the results, or the final conclusions of this manuscript. The manuscript will be updated. The authors would like to apologize for any inconvenience caused. All changes have been reviewed and verified by the Academic Editors."} +{"text": "In the original article, there was a mistake in In the original article, there was a mistake in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :y-axis is not labeled in the published figure.The authors note that The correct version of The authors would like to apologize for any inconvenience caused to readers by these changes."} +{"text": "In the original article, there was a mistake in the legend for In the original article, there was a mistake in the legend for In the original article, there was a mistake in The authors apologize for these errors and state that these do not change the scientific conclusions of the article in any way."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The correct legend appears below.In the original article, there was a mistake in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake: a duplication of one dot plot in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to this paper . Due to The correction does not change the scientific conclusions of the article in any way.The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author information has been updated to correct the errors. The errors do not affect the conclusions of this article. We apologize for the errors and for any confusion they may have caused.In the published paper"} +{"text": "The author wishes to make the following correction to this paper .In the original article, there was a mistake in the calculation of the antioxidant activity measured by ABTS assay for runs of the experimental design b. All vaThe authors apologise for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :In the original published article, there were mistakes in The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :In the original article, there was a mistake in The authors apologize for any inconvenience caused and state that the scientific conclusions remain unaffected. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper .In the original publication, there was a mistake in the legend for There was an error in the original article in There was an error in the original article in The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "In the original article, there were inconsistencies when comparing one by one the panels of Corrections have been made to The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following the publication of the original article , it was The table and caption have been included in this correction, and the original article has been corrected."} +{"text": "This has now been corrected in the article online, and the authors regret the error."} +{"text": "It has come to our attention that there has been an error in the previous work . Due to The data in"} +{"text": "The authors wish to make the following corrections to their paper .In the original publication, there was a mistake in"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the Funding statement. The correct number and name are as follows:This work was supported by the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy .The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following the publication of the original article , the autThe correct title is included in this Correction and has already been updated in the original article."} +{"text": "D is the dimensionality of the model (6 in our case).There was an error in the original article . The var"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologise for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The correct In the original article, there was a mistake in Additionally, there was a mistake in the caption for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "B are wrong. The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The Editor wishes to issue an expression of concern for this article .Contrary to the statement included in the article, ethics approval for the study was provided by Mekelle University, not Aksum UniversityContrary to the statement included in the article, the study was conducted between February 2016 and November 2016Contrary to the statement included in the article, the data used and analyzed during the current study are not availableThe authors have not been able to provide redacted consent forms to confirm that informed consent was obtained from the study participants.After publication of this article it was brought to the Editor's attention that:Neither of the authors provided a statement on whether they agree to this Expression of Concern or otherwise."} +{"text": "In the original article, there were two mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The second image of bottom panel of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :According to our previous researches , in a DLSC, detonation waves that propagate in the LE are no longer centered at the From the geometric relationship in In the subsequent research process, we found that there was no need to calculate the values of R is the curvature radius of the liner):For the calculation of the incident angle of the detonation wave, when When From the geometric relationship in Since this part only introduces the collapsing process of the liner in the figure, it has not been theoretically calculated and this part has no influence on the main research ideas and contents of the paper. The modification in this section does not affect the subsequent numerical simulation analysis and experimental results.We apologize for the inconvenience caused to the readers by our mistakes."} +{"text": "Since its introduction as a methodological tool to study social behavior under the Diamond Grant programme financed by the Ministry of Education and Science of Poland. The research has been supported by a grant from the Priority Research Area (FutureSoc) under the Strategic Programme Excellence Initiative at the Jagiellonian University.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The authors wish to make the following correction to . The heaThe authors would like to apologize for any inconveniences caused to the readers by these changes."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "After publication of this article , concernThe authors recognize the weaknesses present in the analytical approach used in this article that were uncovered after the paper was published; an inadvertent error led to results which were significant and specifically affects the results shown in Figs 2 and 6, and from which some of the conclusions of the article were derived.PLOS Genetics Editors retract this article.In light of the above issues with the analytic approach and the concern that a number of key conclusions are not fully supported by the published analyses in , the autAll authors agreed with the retraction."} +{"text": "In the original article, there was an inadvertent mistake in the preparation of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , the autAll the changes that were requested are implemented in this correction and the original article has been"} +{"text": "The authors wish to make the following corrections to this paper :Changes in figures due to mislabeling. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "After reviewing these requests, the Editors feel the findings of the manuscript can no longer be relied upon and have decided to retract the paper. The corresponding author has agreed to the retraction."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Figure 1 was accidentally duplicated in the proof stage. The correct In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors are in agreement that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused."} +{"text": "Subsequently to the comments raised by the reader, the authors themselves contacted the Editorial Office to request a retraction of the above paper on account of not being to reproduce the results shown in the Oncology Reports, and in line with the authors\u2019 own request, the Editor has decided that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "We acknowledge the points raised by Hodac and Wittekind and woulWe thank the authors for the opportunity to discuss our findings in more detail. A more in-depth comparison between our estimates and the one provided by is limit"} +{"text": "The authors wish to make the following correction to this paper : In the The original version of It should be replaced with the following We stress that these errors were purely due to human error and oversight; all corrections done do not affect or change the written proportion of the figure legend, interpretation of the results, or the final conclusions of this manuscript. The manuscript will be updated. The authors would like to apologize for any inconvenience caused. All changes have been reviewed and verified by the Academic Editors."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following the publication of the original article , the autThe correct title is included in this Correction and has already been updated in the original article."} +{"text": "The authors wish to make the following corrections to this paper :In the last row of In the last row of The new The authors would like to apologize for any inconvenience caused to the readers by these changes. The original manuscript has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "MW361337 and MW361342.There is an error in the Data Availability statement. The correct accession number for ALS and psbA sequences are The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there is an error in the Funding statement. The correct number for the National Institute of Health is R01GM141329. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there were mistakes in The authors apologize for the errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The author wishes to make the following correction to the above paper: . In the The author apologises for any inconvenience caused to the readers by these changes. These changes have no material impact on the conclusions of our paper. The original article has been updated."} +{"text": "The authors would like to update the The changes do not affect the scientific results. We apologize for any inconvenience caused to the readers by these errors. The manuscript will be updated with a reference to this Erratum."} +{"text": "The author wishes to make the following correction to this paper :In the original article, there was a mistake in The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper :In the original article, there was a mistake in"} +{"text": "Foods Editorial Office would like to update the error in the original published version [The version . The TabWe would like to apologize for any inconvenience caused to the authors and readers by this error. We will update the article, and the original version will remain available on the article webpage."} +{"text": "In the original article, there was a mistake in The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The original version of the article unfortunThe other data and the conclusion in the publication are real and reliable.It has been corrected in this correction.The correct version of Fig."} +{"text": "In the original article, there was a mistake in There was also a mistake in The authors apologize for these errors and state that these do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make a change to the published paper . In the The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "Following the publication of the original article , the autThe correct title is included in this Correction and has already been updated in the original article."} +{"text": "Since the publication of the original article , the fouThe correct name is included in the author list of this Correction and has already been updated in the original article."} +{"text": "Consequently, all estimates of Cohen's d in In the original article, there were errors in The author apologizes for these errors and states that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the figures and captions as published. The images were in the incorrect order and did not match the figure captions. The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a formatting issue in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following the publication of the original article , it was The errors and their respective corrections are shown in Table"} +{"text": "There is an error that needs to be corrected in the Funding and Acknowledgments statements of .The updated information is provided below:"} +{"text": "In spite of the strengths of the article, The potential that exposure to manganese contributed to or confounded theeffects of the four metals on serum prolactin levels in the cohortsstudied by"} +{"text": "We are grateful to Jusko et al. for addressing two concerns raised in our review relatingOf relevance to the area of confounding is a recent publication by We feel that the weight of evidence across a number of studies has come down in support of an effect of low-level lead exposure on children\u2019s intellectual and neurobehavioral function; as stressed by"} +{"text": "We read with interest the article by EHP (The Centers for Disease Control and Prevention (CDC) conducted a thorough investigation into the Fallon cancer cluster; in fact, it was the largest cancer cluster investigation ever undertaken in the United States. The scientists from the CDC and state health departments concluded that exposure to tungsten was not associated with the incidence of childhood leukemia in Fallon . The genEHP . BecauseWe are not questioning the quality of the work presented by"} +{"text": "Jill Gilmore. The correct spelling is Jill Gilmour. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.An author name was incorrectly spelled as The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Prunus persica sequence genome was incorrectly written as . It should be (Verde et al., In the original article, the reference for the The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, Figure 8 and Supplementary Table 2 showed the number for MdRIN to be MDP0000326906. This is a mistake. The correct number is MDP0000366022.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, we neglected to include the Acknowledgments section.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Reason for Erratum:Due to a typesetting error, in Table The publisher apologizes for this error and the correct version of the table appears below. This error does not change the scientific conclusions of the article in any way."} +{"text": "Due to an error during production, the project numbers of the National Natural Science Foundation of China projects in the Acknowledgments Section of the published paper were incWe apologize for any inconvenience caused to the readers or authors by this error. The article will be updated and the original will remain on the article webpage."} +{"text": "In the original article, there was a mistake in Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The American College of Medical Physics (ACMP) and the Journal of Applied Clinical Medical Physics (JACMP) are very pleased to announce that with this issue the JACMP is now an official journal of the International Organization for Medical Physics (IOMP). As an all\u2010electronic journal and with the current non\u2010subscription policy the journal is available and accessible to medical physicists world\u2010wide. From the beginning of publication over two years ago, it was clear that the journal was being accessed in many different parts of the world. About 20% of the manuscripts submitted are from outside the United States, and to date papers from over half\u2010a\u2010dozen countries have been published. It has been the editorial policy of the journal to encourage this participation, and this agreement to become an official journal of the IOMP will further strengthen our ties with the international community of medical physicists.This concept was initiated by the Board of Editors a year ago and was presented to the Board of Chancellors of the ACMP at the annual meeting in June of 2001. With their concurrence the Editor\u2010in\u2010Chief proceeded with discussions with Gino Fallone, Chairman of the IOMP Publications Committee. This resulted in the invitation by Oskar Chomicki, the President of the IOMP, for the JACMP to become an official journal of the IOMP. The ACMP and the JACMP wish to express their thanks to the IOMP and its officials for their constructive discussions that made this possible.Under the terms of the agreement the Editor\u2010in\u2010Chief of the JACMP will be an ex officio member of the IOMP Publications Committee and a representative of the IOMP will be invited to attend the Editorial Board meetings of the JACMP.The ACMP and the JACMP look forward to many years of fruitful cooperation with the IOMP.Peter R. Almond, Ph.D.Editor\u2010in\u2010Chief"} +{"text": "In the original article, there was a mistake in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Error in Figure/TableIn the original article, there was a mistake in Table The corrected Table The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was a mistake in the Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After publication of the original article , it cameThis error was present in the Methods section of the abstract and in Table"} +{"text": "In the version of this article that was published on PubMed the auth"} +{"text": "Unfortunately it was missed to state that the co-author Rafael Correa-Rocha is as well a Corresponding author of the Review article.The authors apologize for this. This error does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article it was not indicated that Ming Xu was a joint first author. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This mistaken duplication of the gut image has been replaced here and in the Supplemental Information PDF online with the correct image of the ovary from the same dataset. This correction does not change the conclusions of the paper, as both the gut and the ovary are GFP negative. The authors apologize for the error and any confusion it may have caused."} +{"text": "The calculations in the paper were not affected by this error, which has now been corrected in the article online. The authors apologize for any confusion that this error may have caused."} +{"text": "The authors wish to make the following change to their paper . In the The authors would like to apologize for any inconvenience caused. The change does not affect the scientific results. The manuscript will be updated, and the original will remain online on the article webpage."} +{"text": "The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the original article, we neglected to include the funder The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in the legends for Figures The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "It has come to the authors' attention that there is an error in Figure It is important to note that this error does not impact the conclusions of the article in any way, but may confuse readers as the direction of effects depicted in the original figure do not match the text.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, the same graph was used for Figures The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The original version of this article contained a typographical error in the spelling of the author Karolina Tandre, which was incorrectly given as Carolina Tandre. The authors apologize for the mistake. This error does not change the scientific conclusions of the article in any way.The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in the legend for Figure In the original article, there was a mistake in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AK and handling Editor declared their shared affiliation."} +{"text": "In the original article, we neglected to thank the funder National Natural Science Foundation of China, 81625014 to Hui Wang. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author wishes to make the following correction to this paper , and to The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the original article, there were mistakes in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The following changes have been made to the published paper . The pasThese changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In the original article, part of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "After publication of the original article it was bThe correct spelling of the name is included in the author list of this \u2018Correction\u2019 and updated in the original article."} +{"text": "Catharina Merchante was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in the legend for Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Figure 2B. In particular, we inadvertently drew the red oval in the opposite direction to the original data in the references (Tsukano et al., We noticed that there was an error in the illustration in The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Incorrect Funding NumberWellcome Trust is 095787/Z/11/Z to KH. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.There is an error in the Funding statement. The correct number for The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are errors in this article that the authors and publisher wish to correct. In"} +{"text": "National Commission for Science and Technology CONICYT, FONDECYT grant N\u00b0 1141029. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the original article, we neglected to include the funder The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "During submission of the final version of the manuscript for publication, a previous version of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the Funding statement. The correct number for the Russian Science Foundation is 16-15-00258. The corrected Funding statement appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there were mistakes in Figures The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following corrections to their paper :The first affiliation of authors was incorrect in our published paper in Sensors . TherefoThe authors would like to apologize for any inconvenience caused to the readers by this change. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In this published article, there was a labeling error in the graph-legend of Figure The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Gabriel Padilla Maldonado. The correct spelling is Gabriel Padilla. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.An author name was incorrectly spelled as The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "All authors' name were incorrectly spelled as . The correct spelling is . The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The names of two authors were misspelled in the original article as Anthos Chistofides and Kankana Barhdan. The correct spelling of these names is Anthos Christofides and Kankana Bardhan.The authors apologize for this. This error does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The publisher apologizes for the error.There is an error in the XML that is causing the designation of the Corresponding Author to be indexed incorrectly. Chengshui Chen should be designated as the Corresponding Author, and his email is:"} +{"text": "In the original article, the name of the author Rafal Farjo was misspelled as Rafal Fario.The correct spelling appears above. The authors apologize for this error. This does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is a mistake in the values of the y axis of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Missing Funding[Excellence Initiative of the German Research Foundation], to [Sushree Sangita Sahoo]. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the original article, we neglected to include the funder Addition of Affiliation[Sushree Sangita Sahoo]. As well as having Affiliation , she should also have . The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the published article, there was an error regarding the affiliation for The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the Funding statement. The correct number for 81372915 is 81371915. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "However, the percentages listed in the published table do not match up with the mean lifespans listed. The corrected Table In the original article, there was a mistake in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was an error in the first sentence of the last paragraph of this synopsis. The correct sentence is: This research demonstrates that at least a subset of the genes that cause head and brain formation in bilaterians are also differentially expressed in the aboral region of the sea anemone."} +{"text": "Biosensors Editorial Office wishes to report the following erratum to this paper [The is paper . In the The error was introduced during production. We apologize for any inconvenience caused to the readers by this mistake. The manuscript will be updated and the original will remain online on the article website."} +{"text": "In the original article, there was a mistake in the legend for Figure In the original article, there was a mistake in Figure The authors apologize for these errors and state that these do not change the scientific conclusions of the article in any way. The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, we neglected to include the patient consent statement.Written consent to publication was obtained from the patient.The Production office apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors regret to have made a mistake in publishing this paper with an The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Erratum."} +{"text": "In the original work, we reanalysed the data from 14 studies published in a special issue for Social Psychology. Even though we referred to each of these 14 studies in our figures, we failed to include all of them in the reference list. The references that were omitted from the original publication are listed [This correction is to expand the reference list of our publication e listed ."} +{"text": "Unfortunately, the original version of this article was missThe research for this article was funded by the Hamilton Community Foundation."} +{"text": "In the original article, there was a mistake in the legend for Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, older versions of Figures The correct version of the Figures appears below. This error does not change the scientific conclusions of the article in any way.The publisher apologizes for this mistake and the original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The original version had the position of an ethyl substituent and a carbonyl group switched. The figure has now been updated with the correct chemical structure and is shown here and in the article online. This transcriptional error does not affect the conclusions in the Perspective. The authors apologize for this error and any confusion that it may have caused."} +{"text": "The Authors regret that in the above manuscript an acknowledgement to Dr Navita Somaiah was omitted in error. The Authors would like it noted that the following acknowledgement should have been included in the paper:This is a modified version of Kevin Ray's Radiobiology MSc essay which was based on the topic of Dr. Navita Somaiah's lecture. We thank Dr. Somaiah for very helpful comments on the essay and discussion."} +{"text": "There was a mistake in the grant number of the funding as published. The correct version of funding appears below. \u201cThe study was supported by grants from the National Natural Science Foundation of China and the National Basic Research Program of China (2013CB127200).\u201d The authors apologize for the mistake. This error does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the Acknowledgments section. The correct number for National Natural Science Foundation of China is 31471905.In the original article, there was an omission in Figure In the original article, there was an omission and error in the legend for Figure The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Thin slabs of dielectric materials are often tested for their dielectric properties in plane parallel plate capacitors. When surface conductivity is present, as for instance in freshly split mica, losses not connected with the bulk of the material arise. The present paper deals with the general theory of such measurements. The system is reduced to an assembly of lumped elements superimposed on distributed transmission lines. The treatment includes the presence of possible airgaps underneath the plates of the test condenser. It is shown that such losses depend on the reciprocal square root of the frequency. Losses due to this effect cannot be eliminated by guard ring measurement and much of the published data on the losses in mica must be reexamined in the light of the present work. Similar considerations may apply in the case of other materials. The present paper had its origin in an attempt to interpret the results of some recent work on mica described in a paper by S. Ruthberg and L. FrenkelThe present paper is however a general contribution to the theory of dielectric measurement and the applicability of this theory is not limited to any particular dielectric. Furthermore some loss measurements in mica and other dielectrics should be reexamined in the light of the theory given here to sort out what part of the losses reported may be ascribed to the bulk of the dielectric and what part is in fact due to surface conduction.Before introducing a specific model for theoretical analysis we shall examine briefly the salient features of the results reported in (I).The experimental arrangement used is shown in Suppose now that a dielectric having one slightly conducting surface is placed in the capacitor with the conducting face resting on the smaller disk (arrangement 1).It is clear that current will flow away from the edge of the small disk via surface conduction thus giving rise to losses which are added to the losses incurred in the bulk of the material, and it is shown in (I) that these losses are inversely proportional to the square root of the capacitance of the capacitor formed in the manner described above.11 \u03a9 while the capacitance across a typical sample is 10 \u00b5f per cm2 thus the resistive component of the impedance along a square of 1 cm edge is in the order of 1011 \u03a9 while the shunting impedance across the sample to ground at 1000 c/s is of order 107 \u03a9. The edge current is therefore quickly attenuated. This fact, as is pointed out in (I) makes it impossible to exclude such losses by means of guardring methods.The depth of penetration of this edge effect is quite small. This may be seen as follows: A typical value of the surface resistance on freshly split micaSuppose now that the sample is reversed so that the conducting surface is resting on the large, grounded plate (arrangement 2). In this arrangement the field lines all cross the conducting surface at right angles and there are no losses due to surface currents. Since, however, the conductive layer on the surface will also have transverse conductivity one might expect some losses to occur in this case also. The value of the losses in the two arrangements as well as their dependence on the thickness of the dielectric and on the frequency used are subject to physical and instrumental interpretation.In attempting to explain the losses in the transverse field (arrangement 2) in terms of the physical properties of the surface layer one runs into difficulties. In particular the magnitude of the losses is such that one must assume either a dielectric constant smaller than 1 or a thickness of the layer of the order of millimeters. Neither of these conditions is reasonable.proportional to the capacitance of the piece when measured with the fresh side in contact with the large plate (arrangement 2).The loss induced by splitting is inversely proportional to the square root of the capacitance of the piece.If the fresh side is placed in contact with the smaller plate the losses increase due to the edge effect. This difference in loss is found to be All induced losses vary as the inverse square root of the frequency.The salient experimental features which any theory of this effect must explain are listed below.The order of magnitude of the losses with the two arrangements is the same.One further feature of the experiments must now be described since it provided the clue for the present solution of the problem. If one examines the capacitance of the test capacitor with progressively thinner pieces of the mica between the plates one finds upon plotting the inverse of the capacitance versus the thickness of the dielectric that the resulting straight line does not go through the origin but has, at zero thickness, a positive intercept. This indicates that in practice there is a fixed effective airgap between the plates of the test capacitor and the dielectric. Causes for the airgap may either be inherent in the mica surface or of an instrumental nature. Whatever its origin however the existence of the airgap suggests that surface currents will occur also when the lossy surface is exposed to the large plate since there will be currents along the surface wherever the surface contact with the plate is interrupted. In (I) the existence of the gap was taken into account by a correction applicable for measurements in uniform airgaps but no actual losses at the contact edges underneath the plates were assumed to occur.The magnitude of the correction is quite large and corresponds, for thin samples, to airgap thicknesses amounting to several percent of the thickness of the specimen under test. Consequently the losses associated with this type of contact current cannot be neglected.We are now ready to set up a model representative of the arrangement described above. In practice there may be many areas of contact under the plates and their shape and thickness may be quite varied. Remembering however that the attenuation is quite rapid and that the losses in the various gaps may be summed we need to treat only one typical case, i.e., the loss in a cavity under the plates. It will be easily seen that the edge loss is only a special case of the general model, namely the special case where the airgap capacitance has gone to zero.A represents the region beyond the edge of the smaller plate where the capacitance of the sample is in series with the resistance of the surface. The region B represents the area under the small plate where the resistive path is shunted by the effective airgap. C1 is the capacitance across unit area of the sample, R is the surface resistivity of a unit square of the surface and C2 is the capacitance across unit area of the airgap.The equivalent circuit with the airgap under the plates is indicated in Since the edge effects are confined to a small area near each contact edge one may regard the surface near the edge as forming a part of an infinite parallel plane transmission line, of width equal to the length of the respective edge. In the case of the edge of the upper plate this length is the circumference of the plate but under the airgap one cannot determine the length of the contact edges directly. The qualitative features of the model do not depend on the length of these edges however, and the actual lengths required to account for the phenomena described in (I) are of the order of the plate circumference which is entirely reasonable.V is suddenly applied to the upper plate. The potential V will be established across the entire upper plate with a speed close to the speed of light and the surface of the mica will assume a potential determined by the capacitance divider consisting of C1 and C2. After a time determined by the time, constant (C1R) the surface of the dielectric will however reach the potential V by conduction along the surface. Our assumption now implies that this time is long compared to the time required to establish initial equilibrium in the upper plate.Because the attenuation is very high we may assume that the characteristic inductance of the line is negligible and that the progress of the wave into the line is slow. The progress of the signal along the metal plates by contrast is infinitely fast. These assumptions may be made plausible as follows: Assume that a potential B.In practice a sinewave in a frequency range from 10 to 1000 c/s is used for this experiment and the upper plate is therefore at potential:sV and the surface current Is in order to find the current into the line, Is. To this we will add the current flowing at any time into the airgap. This current is determined for each point x on the surface by the potential difference (V(t) \u2014 sV.). The airgap current must therefore be obtained as an integral over the entire line. This transmission line is described by:Our plan of attack is the following. We shall establish transmission line equations for the surface potential sx, V must approach a fixed value.x=0\u03b1 + ik)The solution can easily be guessed. We note that for large values of C2 via the metal surface above the airgap. This current is given by:z is the extent of the line.We must next calculate the real part of the current entering the capacitance sV this becomes:Using our solution \u03b1 may be found from B consists of the real parts of We are however interested in the general case and particularly in the real amplitudeA, C1 is unchanged and C2 = 0 so that from In section C2 but since we can only measure an average value of C2 we proceed as if C2 were the same at all points, thena is the area of the capacitor, i.e., the area of the small plate.We must next determine the total current in the capacitor so as to form the loss factor. This current will arise from contributions of many sections of the capacitor having various values of A and B of We are now in a position to calculate separately the loss tangents due to sections C2A\u03d5 thus confirming the remainder of the observed dependence on capacitance.For large values of C1 and C2 are generally of the same order, but it must be remembered that the correction as used in (I) is now included in In practice the approximations It also follows from The final question arises whether the effective airgap is physical or instrumental. If it were physical we would have to suppose that the mica surface is uneven to a sufficient degree to cause the effective airgap. If the explanation were instrumental one would have to suppose that the mica sample, though smooth, did not make good contact with the plates perhaps because of a warping in the plates. In any case it is hoped that the theory presented here will be generally useful in the measurement of dielectric properties of thin samples.The present work indicates that whenever thin slabs of material are examined for loss characteristics, one must expect disturbing influences due to surface losses. These generally depend on the inverse square root of the frequency. Though the theory is developed specifically to account for a rather esoteric experiment with mica, its general significance for dielectric measurements is obvious."} +{"text": "Missing Funding NumberThere is an error in the Funding statement. In the original article, we neglected to include the number of the funder Italian Association for Cancer Research, AIRC IG 2014\u201415438. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The rubber hand illusion is a bodily illusion in which participants perceive a fake hand to be part of the body and 50 s (Exp. 2) hand as part of the own body.The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The correct period was the January\u2013September period. Third, the statement that there was a higher proportion of articles about suicide by charcoal burning than about suicide by hydrogen sulfide violating the elements of violation score was incorrect. The correct statement is that there was a higher proportion of articles about suicide by hydrogen sulfide than about suicide by charcoal burning following the implementation of guidelines on reporting suicides in the media; the exceptions concerned reporting the suicide method and not reporting the poor condition of the suicide survivor.We wish to make the following three corrections to the published paper . First, We apologize for any inconvenience caused to the readers by this error. The article will be updated and the original will remain on the article webpage."} +{"text": "There is an error in the caption for There is an error in the caption for"} +{"text": "It has come to our attention that Figure 3 of the title paper containsNanomaterials that this issue was not detected earlier and wish to thank the reader who brought this issue to our attention. Nanomaterials is a member of the Committee on Publication Ethics (COPE) and strives to uphold the highest ethical standards; extensive manipulation of images is not acceptable and we are committed to taking appropriate action when such cases are reported.We apologize to readers of"} +{"text": "Sequences of the primers to amplify 4 of the CpG sites were wrong. The corrected Table In the original article, there was a mistake in Table The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Due to an error during production, the duration of the data collection in the Abstract and Methods sections of the published paper were incWe apologize for any inconvenience caused to the readers by this error. The article will be updated and the original will remain on the article webpage."} +{"text": "The author apologizes for this error. This does not change the scientific conclusions of the article in any way.In the original article, I neglected to include the funder The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors would like to correct two errors in The authors have informed the publisher that they are not able to provide the original raw data for this figure because the lab closed January 2017.However, the authors confirm that the duplicate panels in The authors have provided a corrected"} +{"text": "Following the publication of this article , it was The above have been updated in the original version of the article."} +{"text": "In the original article, there was a mistake in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Concerns have been raised about the integrity of images presented in Figures 2 and S1 of this article. The original blot images from which the figures were made are not available and the first author has indicated that the images in the figures are not from the samples described in the article. At the corresponding author's request, the institutions involved are investigating this matter. The corresponding author and representatives from the institution have advised that the article should be retracted due to the concerns identified about the two figures and the reliability of the underlying data.PLOS ONE Editors retract this article.In light of the concerns raised, the authors and the"} +{"text": "In the original article, the information in the published Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was a mistake in the x-axis label in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The following table should be used.The authors wish to correct the oligonucleotide sequence of The changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Erratum."} +{"text": "Reason for Corrigendum:There is a mistake in the labeling of the two networks plotted in Figure In Figure The corrected Figures are below:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are many possible methods of histopathological audit. Most are expensive of both time and finance. We present an outline of one which is relatively cheap and is based on a meeting that has taken place in Bristol for many years. An analysis of the material reviewed in one year at these meetings indicates that they encompass a wide range of pathology. Furthermore it is possible to get some quantitative indication of the type of lesions that most frequently pose diagnostic problems, and which are thought to be potentially soluble by the opinion of other general histopathologists. The contribution of this type of meeting to histopathological audit is considered."} +{"text": "There was a mistake in the values of the first column of Table The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "We would like to add to the article:In the original article, we neglected to include the specific section The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was a mistake in the strain names of Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This is to inform the readers that the acknowledgement to BBSRC \u2018Open Access funded by Biotechnology and Biological Sciences Research Council\u2019 was captured in the online version and not in print.The publisher would like to apologise for any inconvenience caused."} +{"text": "Due to a typesetting error, Figure The publisher apologizes for this error and the original article has been updated to reflect this. This error does not change the scientific conclusions of the article in any way."} +{"text": "The authors wish to make the following changes to their paper . In the We apologize for any inconvenience caused to the readers by this change. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "The corrected Figure In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There was an error in the placement of some of the decimal points and the thousands separators of Table The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This research has been supported by the European ABBI project (FP7-ICT 611452). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.There is an error in the Funding statement. The correct Name for the Funder is The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author wishes to make a change to the published paper . The titThe change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "The authors wish to make a change to their published paper . The titThe change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "The corrected version of the table can be found below.After publication of the article it was b"} +{"text": "The authors wish to make the following correction to their paper . The autThe authors would like to apologize for any inconvenience caused. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "After the publication of this work , it was The original article has been corrected."} +{"text": "The authors wish to make the following change to their paper .The authors apologize for any inconvenience this may cause.The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "There was a mistake in the Intervention group values at Times 1 and 2 in Table PW was employed at the research site at the time of the study. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The biomedical paradigm is so convincing from a biochemical point of view, and highly efficient in many cases of acute medical problems and emergencies, but unfortunately most patients do not get much better only treated with drugs; they need to do something about their lives themselves. It is highly important for the modern physician to understand the strengths and weaknesses of the modern biomedical paradigm, to understand when and when not to administer drugs to their patients. Often a symptom can be eliminated for a while with drugs, but this is not always good as the patient might need to learn to study the imbalances in life that cause the disturbances and symptoms. For the elderly patient, sometimes life can be extended in spite of the subjective fact that life has come to its end. Sometimes treatment with a drug can teach the patient that quality of life is the responsibility of the physician and not the patient. This learned attitude can give the patient problems later or make them less active in helping themselves (responsibility transfer in the wrong direction).This paper gives a number of examples where medical drugs really are the treatment of choice in general practice and some more doubtful examples of using of the biomedical paradigm."} +{"text": "After the publication of the article , it was A corrected version of Fig."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The data have been removed, and the corrected version of the table now appears online with the paper.The authors apologize for any confusion caused by this error."} +{"text": "In the original article, we neglected to include the partial funding provided to RD by German Federal Ministry for Research and Education and the Egyptian Science and Technology Development Fund. Therefore, the following statement should be added to the acknowledgment:\u201cThis work has been supported by funds to RD by the German Federal Ministry for Research and Education and Egyptian Science and Technology Development Fund (01DH14013).\u201dThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, the online version of Table S1 in Supplementary Material was not the final one. The online version of Table S1 in Supplementary Material has been updated along with the present corrigendum.The authors apologize for this oversight. The updated information does not change the scientific conclusions of the article.The original article was updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the published article, there was an error regarding the affiliation for Jennifer Sartor. As well as having Affiliation 1 and 2 she also contributed equally.The corrected affiliation appears above.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "It was noticed that there was an error in the author list, upon publication of the original article . The nin"} +{"text": "In the originally published article, due to the author's misunderstanding of methods of RNA isolation, one of included studies in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "A widespread epidemic of Zika virus (ZIKV) infection was reported recently in South and Central America. The biggest concern to the ZIKV infection is the significant increase of microcephaly in the fetus born to the infected mother .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors would like to make a correction to their published paper .There was a mistake in the original version of the article in Figure 10A (page 10). The arrangements of bands between groups in the AnxA1 panel were scrambled. The authors have corrected the error as shown in the figure below. The rest of the manuscript and the figure legend do not need to be changed. The authors would like to apologize for any inconvenience caused.Please replace this figure:with the following:The changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "This paper reports on another way in which the outstanding Management problems of the 1990's have been addressed in one particular District in the South West. It indicates the experience of using a particular model over two years and indicates that this could be a useful way forward, both in the District and the Trust of Northern Devon, but also in other Districts facing similar difficulties."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BGH and handling Editor declared their shared affiliation."} +{"text": "The original article containeFurthermore, the error was mistakenly carried forward by the production team handling this article, and thus was not the fault of the authors."} +{"text": "It is well known that the Mathieu series has a wide application in mathematics science. In this paper, we use the elementary method and construct some new inequalities to study the computational problem of the partial reciprocal sums related to the Mathieu series and obtain an interesting inequality and a related identity."} +{"text": "These errors do not alter the findings in the published manuscript, as the correct data were used in all calculations and are displayed in the graphs in each figure. The corrected The authors regret that the original version of The online HTML and PDF versions of this paper have been corrected. The error remains only in the print version."} +{"text": "There was an unnecessary arrow in Figure 1 as published. The correct version of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Christina Warinner was named in the Acknowledgements, which stated that she gave advice with regard to the methodology used in this work. Because the inclusion of her name in the Acknowledgements was done without her knowledge and because she did not concur with the methodology used in this paper, her name was removed from the Acknowledgements at her own request."} +{"text": "It has come to our attention that there is an error in one of the author names for this article . The aut"} +{"text": "Download corrected itemMost of the in-text references in this article are missing from the body of the text.A corrected version with references in place can be found here:"} +{"text": "The correct number for the National Natural Science Foundation of China, 81430090 to LW.In the original article, we neglected to include the funder The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In our mini review article there was an error in the infected macrophage included in Figure The correct version of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "During resubmission of the version of the manuscript, a previous version of Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the published article, there was an error in affiliations 2 and 3. Instead of \u201cThe original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the version of this article that was published on PubMed Central the auth"} +{"text": "There is an error in the Funding statement. The correct number for National High Technology Research and Development Program 863 is No. 2014AA020904. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following change to their paper .The viral strains in the x axis were not ordered correctly in the original The authors apologize for any inconvenience this may cause.The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In the original article, the authors neglected to include the supplementary material. The original article has now been updated and the original data and relevant materials have been added to the section of supplementary material.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "An author name was incorrectly spelled as [Yan Jing]. The correct spelling is [Jing Yan]. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in the Supplementary Data (Data Sheet The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The corrected supplementary material has been updated on the original article page.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The images in There is an error in the caption for"} +{"text": "The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the original article, we neglected to include the funder The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The study by Richter et al. found siThe author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This research has been supported by the European ABBI project (FP7-ICT 611452). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.There is an error in the Funding statement, the name of the funder is incorrect. The correct funding statement is as follows. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, Roshchupkin et al. was not Voxel based morphometry (VBM) was performed according to an optimized VBM protocol (Good et al., The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Geobacter are recently evolved when we submitted our manuscript, which previously demonstrated that the electrically conductive pili of This error does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in the legend for Figure 3 group was missing in the Silybin structure). The corrected Figure In the original article, there was a mistake in Figure The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past co-authorship with the author SN."} +{"text": "An outdated version of Supplementary Table 1 was uploaded to the final version of the paper for publication. This table has not been under peer review and does not include the information described in the paper such as the similarity measurement column. The correct Supplementary Table 1 has now been published in the original article. The authors apologize for this oversight. This error does not change the scientific conclusion of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Nutrients would like to report an error in the published paper [The Editorial Office of ed paper . The affWe apologize for any inconvenience caused to the readers by this change. The change does not affect the scientific results. The manuscript will be updated and the original will remain available on the article webpage."} +{"text": "The authors of the original article mistakenAs such, the authors would like to acknowledge that the study was supported by a grant from the Swiss National Fund (100019_166010)."} +{"text": "Sir - while we have no issues with the data presented in the Letter to the Editor"} +{"text": "The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the published article, there was an error in affiliation . Instead of \u201cThe original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The correct spelling is [Sunderesan]. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.An author name was incorrectly spelled as The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This is now the third edition of a book first published in 1991. The book has grown to two volumes with 30% more information than the second edition. Additional chapters include: The Management of Breast Pain and the Risk of Breast Cancer After HRT. The evolution of Sentinel Lymph Node Biopsy has been addressed and the chapter on Legal Issues Relating to Management of Breast Disease has been expanded.One particularly welcome change has been to adopt an intemational perspective on the references rather than the usual United States-Centric list of references. The text is generally well written, readable and comprehensive, but I found the quality of the reproductions poor and the type face not the clearest to read. This is a shame as it detracts from what is otherwise a good book.All those treating breast disease will wish to have one of the major text books on their shelf. Whether they choose this or the alterative Diseases of the Breast will be a matter of personal choice and pocket. This book is certainly worth considering and had it not been for the poor quality of the illustrations, would be my first choice."} +{"text": "Sir,We congratulate the authors of Dand for theiThe \u2018U\u2019 shaped top of the leg rest which in a way resembles the top of Dand is mobile and can be adjusted in any direction. The height of the leg rest can also be adjusted by sliding it up or down through its fixator, which is attached to the handle along the side of the operating table. The top of the leg rest has a cushion which minimizes the pressure effect during long surgeries and two leg rests can be used if both the lower limbs require preparation simultaneously. We conclude that though Dand is innovative, the above factors make the leg rest more flexible than the Dand with all the advantages of Dand."} +{"text": "A new technique is presented for continuous measurements of hydrogen contamination by air in the upper explosive limit range. It is based on the application of a catalytic combustion sensor placed in a cell through which the tested sample passes. The air content is the function of the quantity of formed heat during catalytic combustion of hydrogen inside the sensor. There is the possibility of using the method in industrial installations by using hydrogen for cooling electric current generators."} +{"text": "It is clarified that the food frequency questionnaire (FFQ) used in the article published in Lipids in Health and Disease , as well"} +{"text": "We agree that the intramuscular route is superior to the subcutaneous in terms of better absorption and we would like to thank Dr. Gazlan for his comment."} +{"text": "The assessment of a screening procedure falls into two parts. The first is the development of a test and the establishment of criteria of specificity and sensitivity. The second stage is that of the application of the test to the general population, demanding attention to the natural history of the disease and to the usefulness and simplicity of the test itself. The decision to organize a screening programme has usually to be taken on the basis of incomplete information and in the setting of a population subjected to constant change. It is the hope of the Committee on Cancer Prevention and Detection of the UICC that the conclusions from the Symposium will prove helpful to all who face such decisions."} +{"text": "There was some discrimination between groups of patients with benign and malignant lesions but there was no clear separation between the groups. A trial of the Cardiff modification of the test failed to discriminate between groups of patients with benign and malignant chest disease. In the view of the authors the MEM test in its present form is not sufficiently reproducible to warrant more general clinical application as an"} +{"text": "The presence of antibody in patients with malignant melanoma is well established if one examines the serum. In this report we have attempted to identify antibody within solid tumours showing that they are rarely present in any appreciable quantity on the surface of tumour cells but can be seen frequently on a number of different types of host cell within the tumours. This is discussed in the light of the role of antibody in the circulation and the possibility of antibody behaving as a blocking factor in vivo."} +{"text": "An evaluation of iron metabolism has been carried out in 23 untreated patients with Hodgkin's disease and 6 patients with other lymphomata. The reduction in red cell life span is related to the stage of the disease. There is an almost universal impairment of iron release from the reticuloendothelial system with a consequent sideropenia and failure of iron delivery to the bone marrow for erythropoiesis. This defect is found in all stages of the disease and is not related to systemic symptoms."} +{"text": "We wish to correct a mistake in the abstract and conclusion of our published paper . In the"} +{"text": "The NCBI protein accession numbers for the sequences employed in the analysis, and the details of the publications describing each sequence, were omitted from the supplementary information in the published article. The authors would like to apologize for this omission and would like to replace the supplementary Table S3 by the one provided here which includes this information: Click here for additional data file.The authors would also like to acknowledge the work carried out by the different groups that described the sequences included in this study, and we have therefore included their relevant details in the revised table."} +{"text": "In a reAlthough Moreover, the symptoms most prominent in the patient described by There are several other limitations of the study by In conclusion,"} +{"text": "A wide range of liquids with different physical properties can be handled with the new dosing system. A detailed description of the new dosing system in terms of function and operation as well as the relevant features and potential benefitsis provided.We present a new automated dosing system developed by the Institute for Automation of the University of Rostock, Germany. The new system is designed for the dosing of chemical liquids in the range of 50 \u03bcL\u20132.5 mL. It is integrated into a miniaturized reactor system to be used in thefield of combinatorial synthesis. The reactor system can be pressurized up to 150 bar and tempered up to 200"} +{"text": "A case of primary squamous carcinoma of the body of the uterus in an 83 year old patient is reported. It is believed to be only the fourteenth adequately substantiated example. This condition apparently occurs at a average age of 5 or more years greater than that at which adenocarcinoma of the endometrium occurs. Our patient may have had generalized squamous metaplasia of the uterine surface epithelium preceding development of this tumour, but the aetiologh of the squamous metaplasia in this case is not clear. One possible factor was her menopause by irradiation 35 years before the tumour developed; an association between irradiation and uterine malignancy is reported but the significance of that association is not certain."} +{"text": "It has come to our attention that since publication of our article , in the"} +{"text": "I was still young and unmarried when Michael Alpers came into Waisa village in 1962 to live there and do research on kuru, which was taking the lives of the people at an alarming rate. I was among the young girls who cleaned up the land to build his house at Yagoenti. My late husband Mr Mabage was a single young man when Michael employed him. He helped in the house and whenever Michael wanted to go out on field patrol he went with him. He was a very handy man in doing fieldwork. He was also asked to go independently to check on kuru patients and report back whenever the symptoms of kuru had changed in the patients.When the medical scientists ran out of food they survived on local vegetables provided by staff members and village people. It was not an easy job in the early days of kuru research, when the people in every village they visited were so often mourning the dead. The staff were kept busy all the time collecting samples and helping the relatives in the funerals of patients. When the research officers left the country my late husband was retrenched and we lived a happy life in Waisa until he died of kuru in 1980."} +{"text": "The authors have withdrawn this article from the public domain because the conclusions drawn may not be supported by the data. In the light of this situation, BioMed Central regrets that this article is no longer available. The authors apologise to all parties for the inconvenience."} +{"text": "The last sentence of the second paragraph in the Discussion section was incorrect. The correct sentence is: \"Here we apply a model that has been described previously [5] to a local population and find that by the end of 2007 approximately half of the number of children predicted to need treatment had started HAART."} +{"text": "Journal of Biology [An error in the PDB code occurred in the article published in the Biology . In the"} +{"text": "This article has been withdrawn from the public domain because of significant plagiarism. In the light of this situation, BioMed Central regrets that this article is no longer available. The authors apologise to all affected parties for the inconvenience."} +{"text": "Dear Editor,This case report is not about the diagnosis of idiopathic central serous chorioretinopathy (ICSC) at the time of presentation as that is really not the objective of our case report.2 The repRegarding the question of the inability of raster line scan to pick up all the pigment epithelium detachment (PEDs) seen on the map, we would like to mention the very basic fact that the raster line scan shows the morphological alterations seen at one particular line scan through which the slice navigator is passing. The changes that are seen on the 3D retinal pigment epithelium (RPE) map are mapping the entire area of the cube and thus all the changes seen on the map cannot be seen in a single line scan. The OCT"} +{"text": "The cell population kinetics of 3 transplantable tumours has been studied under circumstances in which the tumour growth rate was modified by a disturbance of the immunological status of the host. In 2 cases a complete arrest of growth was achieved but in spite of this there was a barely significant change in the median intermitotic time of proliferating cells. The data indicate that growth retardation was associated with a reduction in the proportion of actively proliferating cells and the rate of cell production, with or without an increase in the absolute rate of cell loss."} +{"text": "Cells from the established line NHIK 3025 were exposed to haematoporphyrin derivative and light. After this photodynamic treatment the first interphase of surviving cells was prolonged. Furthermore, a pronounced effect on the progression through the first mitosis was observed. Mainly the duration of metaphase was increased. Some of the cells were irreversibly arrested in mitosis and the cells that were able to complete mitosis after treatment multiplied in the subsequent generations at the same rate as the control. Cells treated in the late stages of the mitosis went out of mitosis at the same rate as the control. This indicates that the treatment with porphyrins and light induces a block in a specific stage of mitosis."} +{"text": "Data are presented on the dermatoglyphics of a group of cancer patients showing that they differ from those of groups suffering from certain other diseases and from those of reported mixed English samples. The differences are much more marked in males than in females. It is suggested that the genes which produce these differences may predispose the cancer patients to their malignancy."} +{"text": "The ability of bacteria to catalyse the nitrosation of secondary amines has been investigated. It has been shown that this may be of importance in people with urinary tract infections living in areas where the concentration of nitrate in the drinking water is high."} +{"text": "This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described."} +{"text": "In the original article, we missed an affiliation for Yufeng Lin. The new affiliations have been added and reordered accordingly.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, the details for reference were incThe original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following correction to their paper . In PaneThe change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to readers by these changes."} +{"text": "In the original article, there was a mistake in Appendix The corrected The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original table in the article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to their paper . In FiguThe authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figures The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original version of our article , Figure The change has no material impact on the conclusions of our paper. The authors would like to apologize for any inconvenience caused to the readers by the change."} +{"text": "There is an error in the Funding statement. The correct number for the Cooperative Research Program for Agriculture Science and Technology Development by Rural Development Administration is PJ013985032018.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "An author's name was incorrectly spelled as Georgios Tschouchnikas. The correct spelling is Georgios Tsouchnikas. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Due to an error during production, the first author\u2019s name of the published paper was incoThe authors would like to apologize for any inconvenience to the readers caused by this error. The article will be updated and the original will remain on the webpage."} +{"text": "The corrected In the original article, there was a typo in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to their paper .There is a mistake in the drawing of the structures of iso-deoxynivalenol. The position of the double bond was drawn incorrectly. The correct position is between C8 and C9 as shown in the new The changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage. We apologize for any inconvenience caused to our readers."} +{"text": "In the Author Contributions statement, the individual contribution of SK was inadvertently missed. SK designed and supervised all the work.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following correction to their paper :We found that The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.There is an error in the Funding statement. The correct number for The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article the disclaimer was not included in the published article. The disclaimer appears below.The conclusions, findings and opinions expressed in this scientific paper reflect only the view of the authors and not the official position of the European Food Safety Authority.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original Supplementary Material has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to their paper . We founThe authors would like to apologize for any inconvenience caused to the readers by these changes which do not affect the scientific results. The manuscript will be updated and the original will remain on the article webpage, with a reference to this Correction."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "These problems with the data led to a dispute among the authors concerning the copyright of the article, leading later to the authors\u2019 unanimous decision to retract this article from the Journal. The authors apologize to the readership of the Journal for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the Funding statement. The correct number for National Science Centre in Poland is 2016/23/B/HS6/00312. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Micromachines would like to make the following change to the published paper [The editorial team of the journal ed paper : The autWe apologize for any inconvenience caused to the readers or authors by this error. The change does not affect the scientific results. The article will be updated and the original will remain on the article webpage."} +{"text": "In the publication of this article , the molThis has now been included in this erratum."} +{"text": "The authors wish to make the following correction to this paper . Due to withThese changes have no material impact on the conclusions of the paper. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Molecules was the subject of a law suit related to authorship. We previously published an Expression of Concern to highlight this fact to readers. A final judgment has now been made and no changes to the authorship are required.The article publisheMolecules and were responsible for all aspects of the reported work.We wish to reiterate that the published authors were found not to be at fault in choosing to publish the article in"} +{"text": "In the original article, there were mistakes in As a consequence of these mistakes, the legends reported in the manuscript for The authors apologize for the errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The Editor apologizes to the authors for this error, and for the inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors apologize for these errors and state that this does not change the results of the research in any way.One of the authors' names was incorrectly spelled. The correct spelling should be: Mingliang Wang. In addition, affiliations 1 and 2 should be changed to The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following correction to their paper . In FiguThese changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to readers by these changes."} +{"text": "It is a paradox if the knowledge produced in this field fails to reach the world of practice. For the practice of implementation to be furthered, we as researchers have an obligation to contribute to improved utilization and translation of the knowledge produced in the implementation science field."} +{"text": "JEM regrets that in the original version of this paper, the labels in"} +{"text": "This clarification does not change the scientific conclusions of the article in any way.The final sentence in the legend of Figure 3 has been reworded to explicitly state the significance of the symbols. The original version of the article has been updated following the highlighting of issues by a third party.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figures 5 and 6 as published. These two figures were inadvertently swapped. The corrected Figures The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. We thank Ruth Nahurira for bringing this to our attention. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following corrections to this paper :2pin2 was incorrectly displayed. The correct version of the table is as follows:In the graphic abstract, the dosage for the BGraphic Abstract:2 and preL3 were incorrectly displayed. The correct version of the scheme is as follows:In The changes do not affect the scientific outcome. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "To address this, we have now replaced the Supplemental Information with the correct version. We apologize for the oversight and for any resulting confusion."} +{"text": "In the original article, there was a mistake in Figure 6 as published. There was an unintentional error in the table composition of Figure 6C. The corrected Figure The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the last sentence of the Results section. The correct sentence is: In the adjusted analyses, political instability was also associated with not getting tested )."} +{"text": "In the original article, due to the authors' oversight, there were several mistakes in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, the name of one of the authors was incorrectly spelled in the reference Lemelle et al., 2008. It was spelled Lamelle et al., 2008 but should be Lemelle et al., 2008.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Raquel Sabino was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Molecules Editorial Office wishes to report the following erratum to this paper [The is paper . In the We apologize for any inconvenience caused to the readers by this mistake."} +{"text": "The original article containeFurthermore, this error was mistakenly introduced by the production team that handled this article and as such, was not the fault of the authors."} +{"text": "In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, Pia Knoeferle was not included as a corresponding author. This has now been rectified. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following correction to this paper : The autThe authors and the Editorial Office would like to apologize for any inconvenience caused to the readers by these changes. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "There are errors in the caption for There are errors in the caption for"} +{"text": "In the original article, all references for in In the original article, references in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Supplementary Figures S1\u2013S6 as published. None of the images for the figures appeared in the final publication. The missing images have been added to the original article's supplementary file.In the original article, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the version of this article that was originally published , some in"} +{"text": "The authors wish to make the following change in their paper . Due to The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "In the original article, there was a mistake in Figure as publiIt is further clarified that the authors reviewed and confirmed the integrity of the original data. Once integrity of these archived data was established, replicate images of leaves from the original samples were selected corresponding to the experimental set-up reported in the manuscript.The authors apologize for these error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Immediately after publication of the original article, the authors found that the incorrect versions of Figure Prasad Neerati was not included as an author in the published article. HPLC data in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "We would like to submit this correction to our published paper . The reaThe abovementioned error in the original article did not have a material impact on the final results and conclusions of our papers. We apologize to our readers for this inconvenience."} +{"text": "In the original article, there was an error in The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Additionally, there was a mistake in The authors apologize for this error and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "European Regional Development Fund: ERDF. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.In the original article, we neglected to include the co-funder The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the published article, there was an error regarding the contributions. Revathi Sekar and Lei Wang should be listed as equal contributors.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is no overlap in the Melilotus accessions used in the two studies.There is a previously published article by some of the same authors that was"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following change to their paper . The imaThe authors would like to apologize for any inconvenience caused. The change does not significantly affect the scientific results. The manuscript will be updated and the original will remain available on the article webpage."} +{"text": "In the original article, we neglected to acknowledge the University of Florida Open Access Publishing Fund in supporting the publication of this manuscript. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make an addendum to their published paper .There was a missing annotation and reference in the original version of the article in the caption of Figure 1 in [The authors wish to mention that some elements from Figure 1 are inspired from Salmi and Jalkanen and modiThe changes do not affect the scientific results.The rest of the manuscript does not need to be changed. The authors would like to apologize for any inconvenience caused."} +{"text": "The authors wish to inform readers that there is an error in the chemical structures shown in The authors apologize for any inconvenience caused to the readers by these changes. We will update the paper and the"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This error does not change the scientific conclusions of the article.The authors regret that there is an error in their code related to the DEMETER2 plots in The corrected plots for DEMETER2 are updated in the figures below (other subplots in The authors would like to apologize for this error."} +{"text": "Gapdh band image used in In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : There were some mistakes in These changes have no material impact on the conclusions of our paper. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "There is an error in the article XML that causes the PubMed citation to be indexed incorrectly. The publisher apologizes for the error."} +{"text": "The authors said it would take a long time to repeat the results and although they do not believe this affects the conclusions, the authors asked to retract the article to avoid misleading readers. They sincerely apologize for the mistake and inconvenience."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in the The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Following publication of the original article , the autThe consequence of this error was that there was a discrepancy between the implications of the Abstract conclusion and that of the main Conclusion of the article.As such, the article has now We apologize for this processing error."} +{"text": "In the original article, there was a mistake in Table The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following corrections to this paper .In After correction, The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The authors regret that there is an error in All other figures and results were accurate in the original paper and were not affected by this correction. The authors would like to apologise for any inconvenience caused."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this omission and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was an error in the Funding statement. The correct Name for the Funder is Bei Shan Tang Foundation. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was an error in the title.Vibrio cholerae.\u201dThe title has been corrected to: \u201cRevisiting the Global Epidemiology of Cholera in Conjunction With the Genomics of The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make the following correction to their published paper . We founThe authors would like to apologize for any inconvenience caused to the readers by this change. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "Mariana Figueiredo Rodrigues was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in Figure 4 as published. The labels on the x-axis were switched around and did not properly align with the plotted data. The corrected Figure The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following change in their paper . Due to The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Erratum."} +{"text": "The authors wish to make a correction to the published version of their paper .The authors apologize to the readers for any inconvenience caused by the change. This change does not impact on the text of the paper or on the overall results or scientific conclusions. The original manuscript will remain online on the article webpage, with a reference to this correction."} +{"text": "In the original article, there were mistakes in Table In all mentioned tables and figures, quantity of amino acids was described in mM instead of \u03bcM. The corrected tables and figures appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "During the course of a review of our publication, an error in the title paper has comeAll co-authors agree with the content of this Correction and wish to apologize for any inconvenience to the readers resulting from this error."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "It has come to our attention that the Western blot data shown in Figure 3 of had beenMDPI is a member of the Committee on Publication Ethics and takes seriously its responsibility to publish only high-quality research. We regret that these issues were not identified earlier and apologize to readers of the journal. We note that this action is not supported by the authors, who maintain that the original results still stand."} +{"text": "The authors wish to make the following correction to their paper . In TablThe change does not affect the scientific outcome. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "In the published article, there was an error in affiliations 1 and 4 as Yangzhou University was not included. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, Francesca Maria Alvino was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the Funding statement. The correct number for National Natural Science Foundation of China is 81673186. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The author wishes to make the following correction to this paper . Due to These changes have no material impact on the conclusions of our paper. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The authors regret that in the original version of this paper, the peptide sequence in"} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following corrections to this paper : We haveThe authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "An author name was incorrectly spelled as Zhengbing Lu. The correct spelling is Zengbing Lu. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors regret that the crop lines in the western blot in Figure\u00a06c were put in the wrong place when the figure was prepared. The corrected version of the figure is:Revising the figure does not alter the densitometry measurements we made or change the conclusions we draw from the data. The authors would like to apologise for any inconvenience caused."} +{"text": "In the original article, there was a mistake in Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This is how the author should be contacted: The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "During the course of a review of our publications, an error in the title paper has comeAll co-authors agree with the content of this Correction and wish to apologize for any inconvenience to the readers resulting from this error."} +{"text": "In the version of this article published earlier, the name of the river Nzhelele was incorrectly spelt as Njelele. The river name has been corrected in the article title and in the \u2018How to cite this article\u2019 section. The authors apologise for any inconvenience caused."} +{"text": "In the original article, there was a mistake in the legend for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was an error in the funding statement. The funding statement in the original article was not formatted according to the funder requirements. It appeared in the original version as: This research was supported by the Medical Research Council (grant number UKP4200 to SZ). It should have been formatted as: This work was supported by the Medical Research Council [grant number UKP4200] to SZ. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Micromachines would like to make the following changes to the published paper [The editorial team of the journal ed paper : The capWe apologize for any inconvenience caused to the readers or authors by this error. The change does not affect the scientific results. The article will be updated and the original will remain on the article webpage."} +{"text": "In the original article, there were two minor mistakes in The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors would like to make the following changes to the published paper : EquatioEquation (13) should be written as follows:The changes do not affect the scientific results. We apologize for any inconvenience caused to the readers by these errors. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The original article containeFurthermore, these errors were mistakenly introduced by the Production team managing this article and, as such were not the fault of the authors."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors have requested that the following changes be made to their paper .In The authors apologize to the readers for any inconvenience caused by the change. Although this typographical error may have misled the reader on the operational definition of the Mediterranean diet according to the PREDIMED screener score, it does not affect the scientific results. The original manuscript will remain online on the article webpage, with a reference to this Correction."} +{"text": "Following publication of the original article , one of The effect of this discrepancy is that the author group is not displayed in the version of the article on the iWe apologize for any inconvenience caused by this processing error."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in the Funding statement. The first funding number is incorrect and should be AICO/2018/123. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Therefore, this article is being retracted and all authors will be prohibited to publish in the Brazilian Journal of Medical and Biological Research in the future."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, a mistake was found in affiliation 1. The state should be CO (Colorado) instead of IL (Illinois). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Concerns have been raised that in Fig 5D of this article several The corresponding author noted that the original data supporting the results in this article are no longer available, and that the authors have been unable to replicate some of the reported results.PLOS ONE Editors retract this article.In light of these issues, the The authors did not reply to the retraction notification."} +{"text": "This has now been fixed in the html version of the paper, the PDF was correct at the time of publication."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a typographical error in Table The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The original Ponceau stain as well as corrected Figure In the original article, there was a mistake in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Unfortunately there was a production error in three of the illustrations of the published work that distorted several graphical elements. The correct versions of Figures The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an error in the Funding statement. The correct number for the Science Technology Department of Zhejiang Province is 2018C04011. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors regret that in their original paper, the Masson\u2019s image of the control group in The online HTML and PDF have been corrected. The error remains only in the print version."} +{"text": "An author name was incorrectly spelled as Madelyne Klugman. The correct spelling is Madelyn Klugman. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There are errors in the caption for There is an error in the last sentence of the second paragraph of the Discussion section. The correct sentence is: Notably, in our analysis, uninsured patients who do not have to go through a prior authorization process had a faster TTI for some cancers."} +{"text": "The manuscript will be updated and the original will remain online on the article webpage. The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way.The authors would like to make the following corrections to the published paper :(1)In t"} +{"text": "In the original article, there were some minor errors in Tables The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following change to their paper . The namWe apologize for any inconvenience caused to the readers by this mistake. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "The corrected In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the published article, there was an error in affiliation 3. The School of Medicine and Kyungpook National University were not mentioned. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "We would like to report an error in a previously published paper . The detPlease note that with the following:Please replace this figure:These changes have no material impact on the conclusions of our paper. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "The following source of funding was not reported in the original publication: National Research, Development and Innovation Office \u2013 NKFIH, Grant Number K 109009. The authors apologize for this error and declare that the amendment does not affect the scientific conclusions of the published studies in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Figure\u00a05 was published incorrectly in the original publication of the article . The corThe authors apologize for the unfortunate error in the figure during publication of the article. It should also be clarified that some of the solid grey graphs in Fig."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected Table 2 appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.In the original article, there was a mistake in Table The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Due to an error during production, the order of the first and last names of the authors are incorrect in the published paper . The corThese changes do not affect the scientific results. The manuscript will be updated and the original version will remain online on the article webpage, with a reference to this erratum. The authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to their paper : In FiguThe authors would like to apologize for any inconvenience caused to the readers by these changes. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "The original Appendix 3, which contained the four reading texts, was removed due to copyright concerns.The enumeration of the appendices has been updated accordingly. The author apologizes for this error and states that this does not change the scientific conclusions of the article in any way. The original article has been updated.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following corrections to their paper . The autThe authors wish to thank the European Union for funding a PhD grant to Federica Moccia.The authors would like to apologize for any inconvenience caused. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "He should have the affiliation The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Table The original article has been updated.Now one can read:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the version of this article initially published, the data and text entries in This correction does not alter the study\u2019s findings of significance or overall interpretation of the study results. The errors have been corrected in the PDF version of the article. The publisher apologises for any inconvenience caused."} +{"text": "The author wishes to make the following correction to this paper . Due to With this corrected table: The authors would like to apologize for any inconvenience caused to the readers by these changes. We will update the paper and the"} +{"text": "In the original article, there was a mistake in Figure The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The corrected In the original article, there was a mistake in The author apologizes for this error and states that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "All procedures were performed according to the guidelines outlined in the institutional Animal Care and Use Committee of the Yokohama City University, Yokohama Japan\u201d should be replaced with \u201cRabbit erythrocyte cells were purchased from a commercial supplier and used following the standard procedure.\u201d The conclusions of the article remain unchanged.The authors wish to make the following correction to their paper . In the The authors would like to apologize for any inconvenience caused to the readers by this change."} +{"text": "In the original published version of this article, the publisher accidentally published a file as a supplement. There should not have been any supplementary file. The publisher apologises for the error. Both the HTML and PDF versions of the article have been updated to correct the error."} +{"text": "It has come to our attention that in the Results and Discussion of the abovearticle, we neglected to cite"} +{"text": "In the original article, there was a mistake in Supplemental Table The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make a correction to the published version of their paper , having"} +{"text": "There is an error in the Funding statement. The correct name of the Funder is Institute of Health Carlos III of Spain . The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make the following correction to this paper : The autWe apologize for any inconvenience caused to the readers. The online version will be updated, and the original will remain available on the article webpage."} +{"text": "The authors wish to make a correction to their paper . The folThe authors would like to apologize for any inconvenience caused to the readers by these changes. The changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction."} +{"text": "There is an error in the Funding statement. The correct number for the National Natural Science Foundation of China is 81230085. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figure 1 as published. The contrast of the figures was too low to be resolved. The corrected Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors wish to make a correction to the published version of their paper .While responding to an editorial request to include additional labelling to The authors apologize to the readers for any inconvenience caused by the change. This change does not impact on the text of the paper or on the overall results or scientific conclusions. The original manuscript will remain online on the article webpage, with a reference to this correction."} +{"text": "The authors wish to make the following change to their paper . The symWe apologize for any inconvenience caused to the readers by this mistake. The manuscript will be updated and the original will remain online on the article webpage."} +{"text": "In the original article, there was a mistake in Figure TG and MP are current or former employees of Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The authors have expressed their concern about the choice of cell line selected for their original experiments, which may account for why their results are no longer reproducible. As a consequence, the authors have requested that this article be retracted from the publication.Both authors on the paper agree to the retraction, and regret the inconvenience that this retraction will cause to the Editor and to the readership of the Journal."} +{"text": "During the course of a review of our publications, an error in the title paper has comeAll co-authors agree with the content of this correction and wish to apologize for any inconvenience to the readers resulting from this error."} +{"text": "In the original article, there was a mistake in Additionally, there was a mistake in The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "While this mistake does not affect at all the interpretation and quality assessment of the experiment, the original image has been replaced by a corrected version in the online article. Both the original and the corrected version of the panel are also displayed below.The authors regret this error."} +{"text": "There is an error in the Funding statement. The correct number for the National Key Program on Transgenic Research is 2018ZX08020002. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Alexandra Granham. The correct spelling is Alexandra Garnham. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.An author name was incorrectly spelled as The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Anjel M. Helms was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in Figure Figure The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In the original article, there was a mistake in The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following correction to their paper . In PaneThe change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to readers by these changes."} +{"text": "The authors wish to make the following correction to this paper . Due to The change does not affect the scientific results. We apologize for the mistake."} +{"text": "The authors wish to make the following corrections to this paper : This change does not affect the scientific outcomes as described in the text. The manuscript will be updated and the original will remain online on the article webpage. The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Each Program of Merit Application goes through a process of review. It is the same regardless if the application is for a gerontology program or a health professions program. In this session, the reviewer perspective will be shared and tips for how to complete an application to provide information in a format that aids the review will be shared."} +{"text": "The authors wish to make the following modification to this paper . 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(NIHR) Oxford Biomedical Research Centre (A.G. and A.O.M.W.) and Newlife (A.G. and A.O.M.W.)."} +{"text": "Qualitative research and pain: Current controversies and future directions. Can J Pain. 2020. doi:Canadian Journal of Pain as it is a duplicate publication of:Please note that this article has been removed from 10.1080/24740527.2020.1809201.Tutelman PR, Webster F. Qualitative research and pain: Current controversies and future directions. Can J Pain. 2020;4(3): 1\u20135. doi:"} +{"text": "Acta Cryst. (2019), E75, 451\u2013455.Corrigendum to et al. , the affiliations were not given correctly.In the paper by Rajeswari"} +{"text": "Dothiorellaviticola, Lasiodiplodia theobromae, Neoscytalidiumhyalinum, Phaeoacremonium (P.) parasiticum, P. italicum, P. iranianum, P. rubrigenum, P. minimum, P. croatiense, P. fraxinopensylvanicum, Phaeoacremonium sp., Cadophora luteo-olivacea, Biscogniauxia (B.) mediterranea, Colletotrichum gloeosporioides, C. boninense, Peyronellaea (Pa.) pinodella, Stilbocrea (S.) walteri, and several isolates of Phoma, Pestalotiopsis, and Fusarium species were obtained from diseased trees. The pathogenicity tests were conducted by artificial inoculation of excised shoots of healthy acid lime trees (Citrus aurantifolia) under controlled conditions. Lasiodiplodia theobromae was the most virulent and caused the longest lesions within 40 days of inoculation. According to literature reviews, this is the first report of L. theobromae and N. hyalinum on citrus in Iran. Additionally, we report several Phaeoacremonium species, S. walteri, Pa. pinodella and C. luteo-olivacea on citrus trees for the first time in the world.Citrus trees with cankers and dieback symptoms were observed in Bushehr . Isolations were made from diseased cankers and branches. Recovered fungal isolates were identified using cultural and morphological characteristics, as well as comparisons of DNA sequence data of the nuclear ribosomal DNA-internal transcribed spacer region, translation elongation factor Citrus species are cultivated in Iran, including sweet orange (Citrus sinensis L.), acid lime (C. aurantifolia (Christm.) Swingle), sour orange (C. aurantium L.), mandarin (C. reticulata Blanco), lemon (C. limon (L.) Osbeck), and grapefruit (C. paradisi Macfad). The most important producing regions in Iran are Mazandaran, Fars, Hormozgan, Giroft, and Kahnouj. Iran is the sixth largest Citrus producer, accounting for 3.3% of the world\u2019s Citrus production, which yielded 4.1 million tons in 2016 [Eutypella have been previously isolated from citrus species, including Citrus limon, C. paradisi, C. maxima, and C. aurantium in Australia, Argentina, Brazil, Coted\u2019Ivoire, Philippines, and USA [Fungal trunk diseases have been studied in detail in grapevine, which are the main biotic factor limiting vineyard productivity and longevity . However and USA ,12,13,14 and USA .Lasiodiplodia [Diplodia, Dothiorella, Neofusicoccum [Neoscytalidium [Phaeoacremonium, is another family of fungi traditionally associated with dieback, canker, and yellowing of various fruit, forest, and ornamental trees, worldwide [Phaeoacremonium species have been identified from woody hosts [Phaeoacremonium species isolated from woody hosts are P. minimum, followed by P. parasiticum [Phaeoacremonium species onto several hosts such as Prunus spp., kiwifruit, oak, and grapevine [Phaeoacremonium species isolated from grapevine have been intensively studied because of their involvement in two trunk diseases, Petri disease in young vines and esca in mature vines [Phaeoacremonium species affecting Citrus spp.Species of Botryosphaeriaceae have a cosmopolitan distribution and have been associated with numerous plant species worldwide ,17,18. Mdiplodia ,21,22,23sicoccum , and Neotalidium ,20 have orldwide ,29,30,31dy hosts . The mosasiticum . Diebackrapevine ,34. Phaere vines ,35. To oIn spring 2014, a severe decline of citrus trees was noticed in some orchards in Bushehr . External disease symptoms included chlorosis of leaves, defoliation, branch and shoot cankers, and dieback. Internal wood symptoms ranged from brown to black wood streaking and black spots to wedge-shaped necrosis, irregular wood discoloration, central necrosis, and arch-shaped necrosis. Many fungi associated with trunk diseases have been isolated from several woody hosts in Iran, including grapevine ,37, pomeIn this study, wood samples were collected from lime (46 trees), sweet lemon (23 trees), sweet orange (22 trees), mandarin (eight trees), sour orange (four trees) and lemon (three trees). Citrus trees showed various external disease symptoms, including yellowing, canker, defoliation, dieback, cracking of the bark associated with gumming, and sooty cankers (form a black powder underneath the bark). Examination of infected branches from symptomatic trees revealed different types of wood discoloration in cross-sections, black to brown streaking in the wood, wedge-shaped necrosis, black spots, irregular wood discoloration, central necrosis, and arch-shaped necrosis .Phaeoacremonium spp., Botryosphaeriaceae spp. Cadophora sp., Colletotrichum spp., Peyronellaea sp., Phoma spp., and Biscogniauxia mediterranea. Thirty-nine isolates were identified as Phaeoacremonium species and characterized by beige to medium brown flat slow-growing cultures on potato dextrose agar and on malt extract agar . Septate hyphae were single or fasciculate, and three types of phialides, variable in shape and size , were recorded in these isolates [Lasiodiplodia, Neoscytalidium, and Dothiorella. Twelve isolates of the phialides fungus were identified as Cadophora sp. These isolates formed flat, felty, and black-olivaceous and white to gray colonies on PDA, and their conidia were ellipsoid or elongate. Cultural and morphological characteristics observed were similar with the description of the Cadophora spp. [Colletotrichum, Peyronellea, Pestalotiopsis, Fusarium, Microsphaeropsis, Alternaria, Trichoderma, Paecilomyces, Aspergillus, Penicillium, Phoma, Biscogniauxia, and Stilbocrea genera.In this survey, 326 fungal isolates were collected from citrus trees . Accordiisolates . Morpholisolates ,17,42. Tora spp. ,44. BasePhaeoacremonium parasiticum and P. italicum were isolated from one tree of C. aurantifolia; P. parasiticum, P. croatiense, and Do. viticola from one tree of C. sinensis, L. theobromae and Neoscytalidium hyalinum from one tree of C. aurantifolia, and C. luteo-olivacea and P. croatiense from one tree of C. limetta. In addition, some fungal species grew from an individual wood segment, such as Stilbocrea walteri and P. fraxinopennsylvanicum from C. limon.No association was found between wood symptoms and fungal species. Dual infections by trunk disease fungi in a single tree occurred. 1\u03b1 (tef1-\u03b1) sequences of Botryosphaeriaceae isolates had 99\u2013100% identity with isolates of Lasiodiplodia theobromae (strain CBS559.70), Neoscytalidium hyalinum (strain CBS 145.78), and Dothiorella viticola (strain CBS 117006). The ITS sequences of the Cadophora isolates had 99\u2013100 % identity with isolates previously identified as Cadophora luteo-olivacea in GenBank (strain CBS 855.69). ITS and \u03b2-tubulin (BT) sequences of Colletotrichum isolates were identical to isolates previously reported as Colletotrichum gloeosporioides and Colletotrichum boninense (ITS and BT: strain CBS:123755) in GenBank. ITS and BT sequences of Peyronellea isolates in our study showed 99\u2013100 % identity with those isolates previously submitted as Didymella pinodella (strain CBS 531.66) in GenBank. ITS and tef1-\u03b1 sequences of Stilbocrea isolates from citrus trees had 99\u2013100% identity with Stilbocrea walteri (strain NQI). Regarding the Biscogniauxia isolates, ITS of our isolates had 99\u2013100% identity with isolates previously identified as Biscogniauxia mediterranea (strain CBS 129072).BLASTn searches in GenBank showed that the nuclear ribosomal DNA-internal transcribed spacer region (ITS) and translation elongation factor Phaeoacremonium were congruent and could be combined (p = 0.225). The Hasegawa\u2013Kishino\u2013Yano model (HKY) with gamma distributed with invariant sites rates (G+I) was identified as the BIC best-fit nucleotide substitution model by the jModelTest for the Phaeoacremonium multi-locus analysis. Maximum likelihood (ML) of the combined ACT-BT regions provided a phylogeny with 98 to 100% ML bootstrap support for all species-level clades, with the exception of P. alvesii , P. griseorubrum , P. roseum (89% bootstrap support), and P. viticola (paraphyletic with regard to P. roseum and P. angustius) . The isolates of the clade 2 grouped together in a polyphyletic clade with 100% bootstrap support with the P. italicum as a closely related species. The BT and ACT sequences of the second clade of Phaeoacremonium isolates were 98% (BT) and 98.77% (ACT) identical to those of P. italicum CBS 137763 . Three nucleotides varied in the ACT region and ten nucleotides in the BT region between the second clade of Phaeoacremonium isolates and the P. italicum CBS 137763 sequences.Datasets of the BT and actin (ACT) alignments of gustius) . The 39 C. aurantifolia are shown in L. theobromae was the most aggressive fungal species and produced the longest necrotic lesions (57.67 mm) on the inoculated shoots followed by Do. viticola (38.17 mm) and P. parasiticum (34.33 mm) and P. rubrigenum (6.00 mm) produced the smallest wood lesions on the inoculated shoots, and no significant differences were observed between these species and the control treatments (3.67 mm).Mean lengths of wood discolorations caused by inoculated isolates obtained from Citrus species on the detached shoots of 4.33 mm) a. In conp < 0.05). L. theobromae also produced the longest wood lesion lengths both in upward (22.34 mm) and in downward (35.33) directions, while S. walteri and P. rubrigenum did not cause any significant necrotic lesion lengths both in the downward and in the upward directions compared to the control treatments on the inoculated shoots. Re-isolation percentages were between 40.0% (C. luteo-olivacea) and 100% on the inoculated lime shoots, and no fungal isolates were recovered from control treatments.All inoculated fungi caused longer basipetal than acropetal lesions on the lime shoots b. Of theCitrus species in Iran. During the last decade, extensive studies have been done on fungal trunk pathogens of fruit trees, including grapevine [Citrus also represents a rich catch host for fungi associated with trunk diseases in this country. Different trunk disease fungi often co-occurred in the same tree and even in the same type of symptom, thus showing the complexity of the etiology of wood symptoms observed. The co-infection of several trunk disease fungi on woody crops could lead to an increase in disease severity compared to the single occurrence of a fungal species, as it has been previously demonstrated on grapevine with Botryosphaeriaceae and Ilyonectria spp. [This study shows the high incidence and severity of fungal trunk pathogens associated with wood decay symptoms of six rapevine ,37, stonrapevine , and pomrapevine ,30, pistrapevine , almond rapevine ,47,48, wrapevine ,50, pomerapevine in Iran.ria spp. .Phaeoacremonium [Phaeoacremonium species, including P. parasiticum, P. minimum, P. rubrigenum, P. italicum, P. iranianum, P. croatiense, P. fraxinopennsylvanicum, and an unidentified species of Phaeoacremonium were recovered from Citrus spp. showing a decline in symptoms. All Phaeoacremonium species reported herein have been found associated with grapevine [P. parasiticum was the dominant Phaeoacremonium species in this study, with 12 isolates collected from C. sinensis and C. aurantifolia. This fungus has previously been reported from C. reticulata in Iran [Actinidia chinensis [Cydonia oblonga, Ficus carica [Olea europaea [Malus domestica [Prunus armeniaca [Prunus avium [Punica granatum [Pyrus communis [P. minimum, P. rubrigenum and P. italicum were isolated only from C. aurantifolia. Similar to P. parasiticum, P. minimum was also reported from a wide range of fruit trees, including A. chinensis [A. deliciosa [C. oblonga [M. domestica [O. europaea [P. armeniaca [Prunus dulcis [P. pennsylvanica [Prunus salicina [P. granatum [P. communis [P. rubrigenum has previously been reported from C. oblonga [O. europaea [P. communis [P. italicum have also been reported from South Africa and this fungus has been isolated from C. oblonga, Ficus carica, M. domestica, O. europaea, P. persica, and P. granatum in this country [P. croatiense was isolated from C. sinensis and C. limetta, while P. fraxinopennsylvanicum was isolated form C. aurantium. Related to fruit trees, P. fraxinopennsylvanicum was previously reported to affect A. deliciosa [M. domestica [P. salicina [Pyrus communis [P. croatiense was only reported from grapevine [Phaeoacremonium spp. affecting woody crops, and provides their first record on citrus trees in the world.Morphological comparisons of trunk disease fungi often reveal an overlap between species in several characters ,16,41. Irapevine ,54,55. P in Iran , and frohinensis , Cydonias carica , Olea eueuropaea ,59, Maluomestica ,58, Prunrmeniaca , Prunus us avium , Punica communis worlwidehinensis , A. delieliciosa , C. oblo oblonga ,58, M. domestica ,28,63, Oeuropaea , P. armermeniaca , Prunus s dulcis , P. pennylvanica , Prunus salicina , P. grancommunis ,28, in Ieliciosa , M. domesalicina , and Pyrcommunis , while PN. hyalinum, Do. viticola and L. theobromae were obtained from citrus trees in this study. Neoscytalidium hyalinum was isolated from C. aurantifolia and C. limetta, Do. viticola was recovered from C. sinensis, C. aurantifolia, and C. aurantium, and L. theobromae was associated with C. sinensis and C. aurantifolia. Several species of Botryosphaeriaceae are known to dieback and branch cankers in Citrus spp. worldwide [Dothiorella viticola has been previously reported to cause gummosis in citrus in California [C. sinensis and C. latifolia Tan. in California [C. sinensis in New Zealand [Citrus sp. in Guilan province of Iran [C. aurantifolia and C. aurantium.Three species of Botryosphaeriaceae, namely orldwide ,68,69,70lifornia and Tunilifornia . This fulifornia , and C. Zealand . Abdolla of Iran . Our stuNeoscytalidium hyalinum has been reported as the most prevalent Botryosphaeriaceae species associated with citrus branch cankers in the desert regions of southern California [C. paradise showing gummosis in California [C. sinensis in Italy [N. hyalinum from two Citrus species, C. aurantifolia and C. limetta. L. theobromae has been previously reported from some Citrus species, including C. limon in Chile [Citrus latifolia) trees in Mexico [C. sinensis and C. aurantifolia. lifornia . This fulifornia and alsoin Italy . Therefoin Chile and Persn Mexico . Our stuCadophora luteo-olivacea were obtained from C. reticulata and C. limetta. C. luteo-olivacea has previously been reported with black vascular streaking and a decline in the symptoms characteristic of Petri disease on grapevine [Cadophora species involved in trunk diseases of trees. This is the first time that C. luteo-olivacea has been found on Citrus spp.In the current study, 12 isolates of rapevine ,54,75,76rapevine , and frorapevine . Aside fBiscogniauxia are reported from forest trees, mainly from Quercus spp. [B. pruni and B. granmoi on Prunus padus [B. marginata on M. communis [B. rosacearum on P. communis, C. oblonga and Prunus domestica [B. capnodes on Averrhoa carambola [Biscogniauxia mediterranea is known to be the causal agent of charcoal cankers on a wide range of trees worldwide, in particular Quercus spp. [C. sinensis [Quercus castaneifolia [Zelkova carpinifolia [Q. brantii [Amygdalus scoparia [Most species of the genus cus spp. ,79,80. Sus padus ,82, B. mcommunis , B. rosaomestica , and B. arambola . Biscogncus spp. . In Iransinensis , along wneifolia , Zelkovainifolia , Q. bran brantii , and Amyscoparia .Stilbocrea walteri were isolated from C. aurantifolia, C. aurntium, and C. limon. This species was originally reported from dead corticated branches of Quercus ilex in Portugal [Citrus species worldwide.In the current study, eight isolates of Portugal , and to Peyronellea pinodella (Didymellaceae) is a destructive necrotrophic pathogen on some plant families, including Fabaceae, Amaranthaceae, Asteraceae, Amaryllidaceae, Appiaceae Rubiaceae, Malvaceae, Poaceae, and Polemoniaceae [P. pinodella on Citrus species and this is the first data on the occurrence of this species on C. sinensis and C. aurantifolia.oniaceae . To dateColletotrichum were found to be associated with trunk diseases of citrus trees in this work, C. gleoesporioides on C. sinensis and C. limetta and C. boninense on C. limetta. Several species of Colletotrichum are associated with fruit and leaf anthracnose diseases of Citrus species; however, other diseases such as twig and shoot dieback caused by Colletotrichum spp. have been documented on citrus trees [Colletotrichum gloeosporioides has been reported from a wide range of fruit trees such as strawberry, olive, almond, mango, apple, avocado, and citrus [C. boninense has been associated with fruit and leaf anthracnose on citrus trees [Colletotrichum species have been isolated and reported from stems of citrus trees in Iran. These included C. karstii from C. aurantifolia and C. sinensis and four species, C. gloeosporioides, C. novae\u2013zelandiae, C. siamense, and C. fructicola from C. sinensis [C. gleoesporioides and C. boninense from branches of C. limetta.Two species of us trees ,93. Colld citrus . This fuus trees ,96. Accosinensis . TherefoM. olivacea were obtained from sweet orange. This fungus has been reported from various plant species worldwide. This taxon has previously been isolated as an endophytic species from P. persica [Pinus sylvestris [Microsphaeropsis olivacea has also been isolated and reported from some woody plants, such as Prunus cerasus, P. avium [Quercus brantii) [M. olivacea on citrus trees. Several isolates of Fusarium, Pestalotiopsis, Phoma, Penicillium, Aspergillus, Trichoderma, and Alternaria species were also obtained from Citrus species in this study. Therefore, more studies are needed on these taxa in order to elucidate their potential impact on citrus trunk diseases.In our work, six isolates of persica , from xylvestris and Chillvestris . Carlucclvestris . MicrospP. avium , and Perbrantii) in Iran.L. theobromae was more virulent on lime shoots than other species. In contrast to our results, Bautista-Cruz et al. reported that L. theobromae was the least virulent species when inoculated in Persian lime branches [L. theobromae has been considered the most aggressive species on Eucalyptus [Lasiodiplodia theobromae was considered an important pathogen on greengage, sour cherry, peach, apricot, cherry [Citrus species showing a decline in symptoms. Further investigations are needed throughout the citrus orchards to determine the potential impact of these fungi on citrus decline.Pathogenicity of selected fungal species in detached shoots of lime tree were confirmed in the current study. Results revealed that branches . Severalcalyptus ,105, gracalyptus ,106, andcalyptus . Lasiodi, cherry , and wil, cherry in Iran.C. limetta), and lemon showing yellowing, defoliation, canker, dieback, and gummosis. In total, 325 wood samples were collected from branches of 106 symptomatic trees (15- to 35-year-old) in 27 orchards. A map with the point locations of the sampled orchards is shown in During 2014 and 2015, several field surveys were performed in important citrus-producing regions of Bushehr province, Tallhe and Tang Eram. This province is located in the south of Iran, within 28.7621\u00b0 N latitude and 51.5150\u00b0 E longitude. Symptomatic wood samples were collected from various species of citrus trees including, acid lime, sweet orange, mandarin, sour orange, sweet lemon and the main microscopic structures [Cadophora isolates was based on the colony and micro-morphological structures, such as conidiogenous cell size and shape, and conidia. The remaining fungal isolates were identified based on available identification keys and published papers [All fungal isolates were identified initially to the genus level based on colony morphology and main microscopic structures using published articles and descriptions. Botryosphaeriaceae isolates were identified based on colony appearance and conidial morphology ,108. To nd size) ,57,109. d papers ,113,114.\u00aeGenomic DNA Extraction Kit following the instructions of the manufacturer. Four primer sets, ITS1/ITS4 [tef1-\u03b1, BT and ACT genes, respectively. The identification of Botryosphaeriaceae isolates was confirmed by the sequencing of ITS and a partial sequence of tef-1a. For Phaeoacremonium isolates, a partial sequence of BT and ACT genes were amplified and sequenced. Molecular identifications of other isolates were confirmed by sequence analysis of ITS , BT (Colletotrichum and Peyronellea isolates), or tef1-\u03b1 (Stilbocrea isolates). The polymerase chain reaction (PCR) was performed in a Techne TC-312 Thermal Cycler , as described by Hashemi and Mohammadi [https://www.ncbi.nlm.nih.gov/) was initially used to identify fungal species.Identities of representative isolates were confirmed using molecular data. Fungi selected for molecular studies were grown on PDA for 10 to 15 days at 25 \u00b0C in the dark. DNA was extracted using an AccuPrepTS1/ITS4 , EF1-728TS1/ITS4 , T1/Bt2bTS1/ITS4 ,118, andTS1/ITS4 were useohammadi . For eacPhaeoacremonium spp. obtained in this study, a phylogenetic analysis was carried out for the Phaeoacremonium spp. isolates. Sequences from citrus in Iran were aligned with sequences available in GenBank/NCBI. These were compared using MAFFT sequence alignment program v. 6 [Pleurostoma richardsiae CBS 270.33 was included as an outgroup. Phaeoacremonium sequences obtained in this study were submitted to GenBank/NCBI (http://treebase.org).Due to the broad range of ram v. 6 with ex-ram v. 6 . PAUP veram v. 6 was usedram v. 6 was usedram v. 6 was usedram v. 6 . Pleurosank/NCBI and the C. aurantifolia under controlled conditions. These include Do. viticola, P. italicum, P. minimum, P. rubrigenum, and P. parasiticum isolated from C. aurantifolia, L. theobromae, and Col. gloeosporioides obtained from C. sinensis, C. luteo-olivacea, and N. hyalinum recovered from C. limetta, P. fraxinopensylvanicum from C. limon, P. iranianum from C. reticulata and S. walteri isolated from C. aurantium. The shoots (38\u201340 cm in length and 2\u20132.5 cm in diameter) were surface-disinfected with alcohol (96%) and then were wounded at the uppermost internode with a 4-mm cork borer. To assess pathogenicity, wounds were inoculated with a 4-mm colonized PDA agar from 14-days-old cultures. All inoculated sites first were covered by moist cotton and then were wrapped with a strip of Parafilm . Six shoots per fungal isolate were used, and an equal number of shoots were also inoculated with 4-mm non-colonized PDA agar plugs for negative controls. Inoculated shoots were arranged at random, including the six inoculated shoots per isolate. Inoculated shoots were placed in moist chambers and incubated at 25 \u00baC. The total, upward, and downward lesion length data were evaluated individually, 40 days after inoculation. Recorded data were checked for normality of distribution by means of the Shapiro\u2013Wilk and Kolmogorov\u2013Smirnov tests. The data were subjected to analysis of variance (one-way ANOVA) using SAS v 9.1 . The lea"} +{"text": "R. Soc. Open Sci.7, 191848. (Published online 18 March 2020) (doi:10.1098/rsos.191848)This correction refers to an error in the spelling of one of the authors' names. Ching-Shin Chou was given, in place of Ching-Shan Chou. This has now been corrected."} +{"text": "The authors wish to make a change to the published paper . We wishAuthor Contributions: Synthesis and laboratory work, A.O.B.; Writing\u2014original draft preparation, A.O.B. and M.A.A.; Supervision, M.M.H. and W.Z.W.Y.; Writing\u2014review and editing, Y.A.-D.; Formal analysis, M.M.H. All authors have read and agreed to the published version of the manuscript.https://www.mdpi.com/2073-4360/12/6/1305.The authors apologize for any inconvenience caused and the change does not affect the scientific results. The manuscript will be updated, and the original will remain online on the article webpage at"} +{"text": "The quantitative trait loci associated with the immune properties of chickens are of interest from thepoint of view of obtaining animals resistant to infectious agents using marker-assisted selection. In the processof selecting markers for genomic selection in broiler-type chickens, a non-standard genotype frequency of theRACK1 gene allele (SNP Gga_rs15788101) in the B5 line of broiler-type chicken cross Smena 8 was identified andit was suggested that this gene was involved in selection. Therefore, it was decided to investigate the availablepolymorphisms in the three genes responsible for the IgY titer . Molecular typing of singlenucleotide polymorphisms of three loci revealed an approach to fixation of the unfavorable allele of the DMA gene(SNP Gga_rs15788237), an approach to fixation of the unfavorable allele of the RACK1 gene and the prevalence ofthe favorable CD1B gene allele (SNP Gga_rs16057130). Analysis of the haplotypes revealed a strong linkage disequilibriumof these genes. This suggests that these genes experience selection pressure. Analysis of the protein-codingsequences of the CD1B and DMA genes of various breeds of chickens revealed a negative selection of these genes.In order to understand whether the fixation of the studied alleles is the result of artificial selection of the B5 line ofthe cross Smena 8, an analysis of similar loci in layer chickens Hisex White was carried out. The frequencies of thealleles at the loci of the CD1B gene (Gga_rs16057130) and the RACK1 gene (Gga_rs15788101) in the Hisex Whitechicken genome differ from the frequencies of the alleles obtained for chickens of the B5 line of the cross Smena 8.It can be assumed that the fixation of the allele in the DMA gene (SNP Gga_rs15723) is associated with artificial ornatural selection, consistent in broilers and layers. Changes in the loci Gga_rs16057130 and Gga_rs15788101 in theB5 line of the Smena 8 chickens are most likely associated with artificial selection of broiler productivity traits, whichcan subsequently lead to fixation of alleles at these loci. Artificial breeding of chickens leads to degradation of thevariability of genes encoding elements of the immune system, which can cause a decrease in resistance to variousdiseases. The study of the negative impact of selection of economic traits on immunity should provide means tomitigate negative consequences and help find ways to obtain disease-resistant animals. Selecting production traits in the broiler chicken has a negativeeffect on the breed\u2019s resistance to infectious diseases and harms their immune competence. On the otherhand, resistant chickens are poor producers, e.g. high leucosisresistance in layers reduces egg yield. The only exclusion tothis rule has been known so far is resistance to Marek\u2019s diseasethat stimulates egg laying . One of thestudies has demonstrated that broilers produce a short-termhumoral response, while layers \u2013 a long-term humoral andstrong cell-mediated response . Anotherstudy claims genetic selection to improve the broiler\u2019s growingtrait reduces the humoral and increases the cell-mediatedand inflammatory responses . Thereare studies proving intensive selection has no negative effecton poultry immune competence . At thesame time, there is a theory saying the resources necessaryfor physiologically normal immunity are taken to provide theproductivity trait in chicken .After it was found out that antibody titers are geneticallyinherited, the certain genes affecting this process were detected. The quantitativetrait loci associated with the immune properties in Gallusgallus belong to different chromosomes . A genome-wide search for associationsallowed one to detect in chromosomes 1, 3, 5, 12 and16 nine single-nucleotide polymorphisms (SNPs) in the lociassociated with total immunoglobulin Y (IgY) concentrationin sera. The most significant five of them are located withina narrow region covering 0.26 Mb of chromosome 16 in theMHC-B locus that determines resistance to viral, bacterial andparasitic infections in chickens. Locus\u2019s variability determinesa breed\u2019s resistance to different pathogens . Keeping in mind that the number of haplotypes in thelocus is almost one order lower in broilers than in their wildancestors, it partially may explain the difference in resistance. The genes of this region may playa crucial role in immune response modulation , so chickens produce IgY to provide their offspringswith an effective humoral response to the most wide-spread pathogens before their own immune system matures . While choosing genomic selectionmarkers in the parental lines of the B5 line / Smena 8 crossbroilers, a nonstandard allele genotype of the RACK1 genewas identified and a suggestion was made that it might beinvolved in the selection process. For that reason, a decisionwas made to study the polymorphisms of all the three genesresponsible for the IgY titer.To isolate the DNA, feather samples from the 100 broilersbelonging to the 79th generation of the B5 line / Smena 8 cross(Cornish breed) bred at Breeding and Genetic Center \u201cSmena\u201dwere collected. To isolate the DNA of layer chickens, thefeather samples of 48 the Hisex White layer chickens bred atthe Zagorskoe Experimental Farm of Federal Scientific Center\u201dAll-Russian Research and Technological Poultry Institute\u201dof the Russian Academy of Sciences were used. The DNAwas isolated from the animals\u2019 quill of 0.3\u20130.5 cm in lengthas it is required by the investigation protocol for the M-sorbkit . The PCR required1.5 \u03bcl of isolated DNA and was performed in real time usingan \u0410N\u041a-\u041c device . The SNPswere typed in two different ways: with the primers containinga modified LNA nucleoside on their 3\u2032 end ; and introducing two different LNA nucleosidesinto the 5\u2032 end of a probe in a position compliment to an SNPbeing studied. While the probe/target mismatch destabilizedthe interaction, the proper positioning facilitated it. This wasdue to the presence of LNA modification that significantlychanged the thermodynamic characteristics of the samples. Using two different channels to detect afluorescent signal enabled us to detect an SNP in a single testtube, increasing the assay\u2019s effectiveness and simplifying datainterpretation. The primer/probe sequences for SNP detectioncan be seen in Table 1.https://www.ensembl.org/index.html . Thelinkage disequilibrium was analyzed using the CubeX webtool and the DNASp v.6 software . The positive and negative selection wasanalyzedin the HyPhy software from the Datamonkey web server (http://datamonkey.org) using the following sequences from GenBank:AB268588.1, AY849318.1, NM_001024582.1, AB204802.1,AY375530.1 for the CD1B gene; AB268588.1, FJ770458.1,NM_001099353.2, HM545127.1, AB426148.1 for theDMA gene; and AY393848.1, M24193.1, NM_001004378.2,CR386189.1, AY694127.1 for the RACK1 gene. Protein secondarystructure errors due to mutations were analyzed onthe Dim-Pred (Disorder inducing mutation prediction) serverat http://www.iitm.ac.in/bioinfo/DIM_Pred/ . The protein 3D structures of corresponding genes weremodeled on the SWISS-MODEL web server at http://www.expasy.ch/swissmod/SWISS-MODEL.html .Such dyes as 6-carboxyfluorescein (6FAM) and 5-carboxyrhodamine6G (5R6G) were used as fluorescent markers,and the BHQ1 dye \u2013 as a quencher. The accumulated data were put through the Ensamble genome browser at SNP typing of the three loci responsible for enhanced IgYtiter in the B5 line / Smena 8 cross broilers was carried out.All the three SNPs were localized within their correspondinggenes. Fixation of the allele Gga_rs15788237 determining thelowest IgY titer in the locus was revealed, as well as that of anunfavorable allele Gga_rs15788101 and the predominance ofa favorable allele Gga_rs16057130. The results of SNP typingcan be seen in Table 2.CD1B gene. The CD1 proteins are a family that is similarto MHC class I glycoproteins that expose alien and nativeantigens, so they can be recognized by T-cells . The ratio of synonymous (dS) and nonsynonymous(dN) mutations in the 5\u2032 coding sequences of the CD1B gene inthe chickens of different origin demonstrated a negative selectionto present in two regions. The analysis performed usingthe HyPhy software showed the gene has two codon- alterationregions that result in amino acid replacement (Table 3).However, while replacing nonpolar valine by alanine may notaffect the protein\u2019s structure and functions, a replacement ofpolar serine by nonpolar glycine may significantly alter boththe structure and the way the protein interacts with ligands.Analyzing the two mutations on the DIM-Pred server demonstratedtheir destructive effect on the protein\u2019s secondarystructure in which the coding glycine occurred to bind thefavorable SNP Gga_rs16057130 allele. 3D modeling of theprotein\u2019s structure revealed no visible changes in case ofmutual replacements.DMA gene. The DMA gene encodes the alpha-chain ofglycoprotein being the receptor to expose alien antigens withspecialized T-cells . The gene\u2019s dN/dSratio suggests there is one negative selection site in this gene(see Table 3). The Ser27Leu replacement does not disrupt theprotein\u2019s secondary structure but can probably affect the wayit interacts with its surrounding and ligands. However, if thesite really presents in the DMA gene, a question rises why theunfavorable allele prevails for the IgY titer. A possible explanationcan be a balancing selection when a positive selection issubstituted by a negative one if the allele frequency becomeshigh. In this case allele fixation never occurs, so they cannotbe regarded either as favorable or unfavorable .In essence, the issue remains open.RACK1 gene. The gene encodes C1, an activated kinasereceptor subunit. Analysis of the gene\u2019s dN/dS ratio revealsno signs of the selection determined by the encoding part ofthe gene, which is hardly a surprise, for this protein is veryconservative and 100% match of that in humans. Thus, thehypothetic reason of RACK1 selection remains unidentifiedand can be predetermined as by the encoding as by theregulation sites in both encoding and non-encoding domains. Since structuralconservation can not be a strong selection factor of itsown , several suchfactors may probably exist.The allele fixation effect that produces extended runs ofhomozygosity as a response to environmental and artificialselection factors has recently been found in chickens . The runs are 3 millionbase pairs on average and contain a certain number of linkedhomozygous SNPs . Finding such runs allowsone to detect the genome regions and genes involvedin both natural and artificial selections. In tropical climate,adaptation of chickens to traditional poultry production leadsto natural selection of birds with favorable genotypes, so thefrequency of corresponding alleles increases in the next generations,affecting the homeostasis and immune system genes. For us to understand if the fixationof studied alleles was the result of artificial selection in theB5 line / Smena 8 cross broilers, analysis of similar loci in theHisex White layer chickens was carried out (Table 4).Similar to the results obtained from the B5 line / Smena 8chickens, the Hisex White layers had an allele Gga_rs15788237fixation in the locus. However, the allele frequencies Gga_rs16057130 and Gga_rs15788101 in the Hisex White genomeare different from the frequencies obtained for the B5 /Smena 8 chickens.Based on the data obtained, an assumption can be made thatthe allele fixation in DMA gene is related to either artificial ornatural selection that is similar for both layer and broiler chickens.The changes in Gga_rs16057130 and Gga_rs15788101loci observed in the B5 line / Smena 8 cross chickens are mostlikely related to artificial selection of the productivity traitstypical for broilers, which in the future may result in completeallele fixation in these loci. While the fixation, the so-calledgenetic hitchhiking can take place when an allele changes itsfrequency not because it is being selected but because it islocated next to a gene being selected . This phenomenon may involve both favorableand unfavorable alleles of the neighboring gene.Thus, the presented experiment has confirmed that artificialselection for productivity traits may possibly affect the immune system of chickens, the effect that was first studiedby J.J. Li et al. (2017). Typing of the IFIH1 and IFIT5 innateimmunity genes has demonstrated an interaction betweenthe production traits and the immune system. It can also beassumed that artificial selection of commercial traits mayresult in passive selection for immune traits. A study to identifyartificial selection regions in chickens detected two immunity genes: BCL2L14 (apoptosis mediator)and CDH13 (encoding protein enhancing immune resistivityto Campylobacter jejuni). Resequencing of the cockfightingchicken genome detected multiple immunitygenes involved in the selection process.All the authors mentioned above reported about the genesbeing involved in selection but not directly related to productivitytraits. However, they did not mention whether favorableor unfavorable alleles were selected. The fact that unfavorablealleles can be selected as well has long been known sinceboth artificial and natural selection increases the frequencyof the rare recessive alleles having a negative effect on viability. This can be exemplified by skeletonand muscle diseases in growing chickens and by multipleovulations in broilers\u2019 adult parents meaningthe corresponding diseased genes are a part of the parentlines. Other negative manifestations of artificial selectionsinclude reduced resistance to infectious disease, pulmonaryhypertension and osteoporosis that can be promoted by negativepleiotropic effect or genetic hitchhiking . A stark example of such unexpected selection resultscan be a 22% body mass increase in the chickens bred fromcrossing the Livorno White lines, which were selected for along term to produce two-yolk eggs .All these data prove that selection affects multiple genes. Inour study, selection of two unfavorable and one favorablealleles of a single trait was observed, which is importantbecause unfavorable alleles can be beneficial for artificialselection. Forecasting of the unfavourability is based on thevariants that greatly affect the phenotype but often turn out tobe unstable in nature. However, in artificial conditions, thesevariants may be quite viable .Artificial selection in chickens leads to degradation of the variabilityof the genes encoding the immune system elements thatmay worsen the birds\u2019 resistance to certain diseases. 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DOI10.1371/journal.pone.0117269."} +{"text": "Scientific Reports 10.1038/s41598-020-66761-9, published online 06 July 2020Correction to: Colletotrichum noveboracense was given as \u2018CBS 146410; AFKH109\u2019 rendering the name invalid due to Arts 40.7 and 40.81. The species is validated herein.In the original version of this Article, in the Taxonomy section, the typification of the name Colletotrichum noveboracense F. Khodadadi, P.L. Martin, V.P. Doyle, & J.B. Gonzalez & S.G. A\u0107imovi\u0107, sp. nov. MB 836581.Scientific Reports 10, no. 11043: 7 (2020).For a detailed description see this Article, Malus domestica cultivar Idared, July 2017, F. Khodadadi & S.G. A\u0107imovi\u0107, BPI 911227.Holotype: The United States of America: New York State, Hudson, from fruit lesion of Ex-holotype culture: CBS 146410; AFKH109.In Table 2, the GenBank accession numbers for GAPDH and GS of PMKnsl-1 in the manuscript, \u2018MN7741093\u2019 and \u2018MN7411007\u2019 now read \u2018MN741093\u2019 and \u2018MN741107\u2019 respectively.Furthermore, the version of this Article previously published contained lower resolution images for Fig.\u00a02. This has now been corrected in the PDF and HTML versions of the paper."} +{"text": "Melophus lathami) is the single species of the Melophus, which was mainly distributed to the south of Asia. The complete sequence of the mitochondrial DNA of M. lathami have been obtained, which consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes (12S rRNA and 16S rRNA), and one control region (D-loop). The nucleotide composition was 30.1% A, 33.0% C, 14.3% G, and 22.6% T. Besides, the phylogenetic tree based on 12S and 16S rRNA was divided into three clades. M. lathami was determined in the second lineage.Crested Bunting ( Melophus lathami) is a passerine bird with widespread in southern Asia . M. lathami is a large dark bunting (17\u2009cm in length) with elongated head crest . We sequenced data by MEGA 6.0 , and one control region. All the protein-coding genes in M. lathami are distributed on the H-strand, except the ND6 subunit gene, rep-origin, and eight tRNA genes , ProtRNA, GlutRNA), which are encoded on the L-strand. In 13 protein-coding genes, the shortest one is ATP8 gene (168\u2009bp) and the longest one is the ND5 gene (1818\u2009bp). For most protein-coding genes, they take ATG as start codons, while ND3 regard ATA as start codons. The control region (D-loop) of the M. lathami mtDNA was 1212\u2009bp in length.Circular complete mtDNA sequence of Emberiza, M. lathami and Passer montanus. Passer montanus was used as outgroup. As shown in E. elegans makes up the first lineage. The second lineage includes three species . The third lineage is composed by E. rutila, E. aureola, E. rustica, E. pusilla, E. tristrami, and E. chrysophrys. M. lathami lies in a separate small branch, in general, it presented a relative close relationship with Emberiza at the molecular level, especially E. jankowskii and E. cioides.We constructed the phylogenetic tree by Bayesian inference (BI) with MrBayes 3.2 (Ronquist et\u00a0al. Mitochondrial DNA, as a powerful and important way to explore genome evolution, helps to infer ancient evolutionary relationships Boore . We expe"} +{"text": "Scientific Reports 10.1038/s41598-019-55572-2, published online 23 December 2019Correction to: The Author Contributions section in this Article is incorrect.\u201cThe late S.-Y.L. conceived the original idea. J.-W.R., S.-Y.L., M.C. and I.K. formulated the method. J.-W.R., J.C., Y.K. and S.-J.P. performed numerical calculation. J.-W.R., J.C., S.R., M.C. and I.K. wrote the manuscript. All authors analyzed the data, discussed the results and provided feedback for the manuscript.\u201dshould read:\u201cThe late S.-Y.L. conceived the original idea for this BEM. J.-W.R., S.-Y.L., M.C. and I.K. formulated the method. J.-W.R., J.C., Y.K. and S.-J.P. performed numerical calculation. J.-W.R., J.C., S.R., M.C. and I.K. wrote the manuscript. All authors analyzed the data, discussed the results and provided feedback for the manuscript.\u201dAlso, this Article contains an error in the Conclusion section.\u201cIn order to obtain the resonant mode functions in TCs designed by conformal TO, we have developed a pure BEM based on the fact that the Green\u2019s functions of interior and exterior regions are known in the RV and the physical spaces, respectively, which are connected by a conformal mapping. For the verification of our BEM, we have respectively, which are connected by a conformal mapping. For the verification of our BEM, we have calculated resonant modes in lima\u00e7on-shaped TCs and compared those with the corresponding results from FEM.\u201dshould read:\u201cIn order to obtain the resonant mode functions in TCs designed by conformal TO, we have developed a pure BEM based on the fact that the Green\u2019s functions of interior and exterior regions are known in the RV space and the physical space, respectively, which are connected by a conformal mapping. For the verification of our BEM, we have calculated resonant modes in lima\u00e7on-shaped TCs and compared those with the corresponding results from FEM.\u201d"} +{"text": "Scientific Reports 10.1038/s41598-018-27279-3, published online 11 June 2018Correction to: This Article contains errors.In the Introduction section, the sentence,19 measured a large number of specimens and found that the key characters of two new species, T. tzvelevii sp. nova and T. joannis sp. nova20, were remarkably similar to T. laxmannii and T. orientalis, respectively.\u201d\u201cFor example, Zhushould read:19 measured a large number of specimens and found that the key characters of two new species, T. tzvelevii sp. nova and T. joannis sp. nova20, were remarkably similar to T. orientalis and, T. laxmannii respectively.\u201d\u201cFor example, ZhuIn addition, Reference 20 was incorrectly given as:Typha L. (Typhaceae JUSS.) from the Far East of Russia and from Mongolia. Feddes Repertorium113, 281\u2013288 (2002).Maveodiev, E. V. Two new species of The correct Reference is listed below:Typha L. (Typhaceae JUSS.) from the Far East of Russia and from Mongolia. Feddes Repertorium113, 281\u2013288 (2002).Mavrodiev, E. V. Two new species of"} +{"text": "Nature Communications 10.1038/s41467-020-18181-6, published online 28 August 2020.Correction to: In the original version of this Article, the DOI for Reference 21, describing protocols for sample preparation and imaging procedures used in this Article, is incorrectly cited as 10.1038/protex.2011.204. The DOI link should be 10.21203/rs.3.pex-1069/v1. This has been corrected in both the PDF and HTML versions of the Article."} +{"text": "Narrow-leaved lupine (Lupinus angustifolius L.), a valuable leguminous crop adapted to a wide range ofclimatic conditions, has a very short history of domestication. For many centuries it was used mainly as a greenmanure, since the success and prospects of the multi-purpose use of the species depend on its breeding improvement,in particular, on a particular concentration of alkaloids in seeds and green mass. The first varieties of scientificbreeding were created only in the 1930s after the appearance of low-alkaloid mutants. Despite wide prospectsfor use in various areas of the national economy, unstable productivity and susceptibility to diseases hinder theproduction of this crop. Obviously, breeders deal only with a small part of the gene pool of the species and limitedgenetic resources, using mainly low-alkaloid (sweet) genotypes to create new varieties. The genetic potential ofthe species can be used more efficiently. At the same time, it is rational to create highly alkaloid (bitter) varietiesfor green manure, while food and feed varietiesshould not lose their adaptive potential, in particular, resistance topathogens, due to the elimination of alkaloids. In this regard, it seems to be a productive idea to create \u2018bitter/sweet\u2019varieties combining a high content of alkaloids in the vegetative organs and low in seeds, which can be achievedby regulating the synthesis/transport of alkaloids in the plant. The paper discusses the current state of use of thespecies as a green manure, fodder, food plant. Information is given on the quantity and qualitative composition ofnarrow-leaved lupine alkaloids, their applied value, in particular, fungicidal, antibacterial, insecticidal, the use oflupine alkaloids as active principles of drugs. Along with promising breeding considerations, the possibility of usingtechnologies for processing raw high-alkaloid materials with the accompanying extraction of valuable ingredientsfor pharmaceuticals is discussed. Information is briefly presented about the genomic resources of the species andthe prospects for their use in marker-assistant selection and genome editing. The narrow-leaved lupine (Lupinus angustifolius L.), alsoknown as the blue lupine, is one of the three Lupinus spp.cultivated in Russia. Along with white andyellow (L. luteus L.) lupines, it is a valuable pulse crop,whose seeds contain 30\u201340 % of protein, up to 40 % ofcarbohydrates, 6 % of oil, numerous minerals, vitamins, andother beneficial ingredients, ranking this species among themost important crops of the present and the future.http://www.fao.org/faostat/en/#data/QC).Today, L. angustifolius is a leader among other cultivatedlupine species in the cropping area occupied worldwide.It is widely cultivated in Northern Europe, countries ofthe ex-USSR, the United States, and New Zealand. Theworld\u2019s leading producer and exporter of this crop is Australia,where the areas under narrow-leaved lupine reach0.6\u20130.7 million hectares, and large funds are invested inits research and breeding. In Russia, in 2018, its productionarea was 35,000 ha, which is not much consideringthe size of the country. However, the Russian Federation isstill among the top ten producers of this crop .Potential uses of narrow-leaved lupine have not yet beenpracticed to the fullest extent. Historically, this crop wasgrown for green manure and animal feed. These days, itsnutritional, pharmacological and phytoremedial propertiesare coming into the sphere of interest, as well as its useas a feed in aquaculture. The prospects of its utilization asa source of bioethanol and naturalfiber are discussed.The uses of narrow-leaved lupine depend on the presenceof secondary metabolites in its seeds and biomass,especially quinolizidine alkaloids responsible for bittertaste and toxic to both humans and animals. Polymorphismof the species\u2019 gene pool in the content of such compounds makes it possible to develop cultivars for a specific purpose.High-alkaloid genotypes are promising as green manureplants and producers of alkaloids for pharmaceutics andmedicine, while low-alkaloid ones may be used for foodand feed purposes.This review attempts to analyze different applicationsof narrow-leaved lupine genetic resources depending onthe content of alkaloids in the genotypes, describe lupinealkaloids and their practical worth, assess the need fortargetedbreeding of specialized cultivars, survey geneticand genomic resources promising for breeding, and discusspossible technologies capable of expanding the crop\u2019s economicpotential.The center of origin for narrow-leaved lupine is the Mediterraneanregion. L. angustifolius occurs as a wild plantmuch more frequently than other lupine species in the OldWorld and is still widespread across the entire Mediterraneanbasin. It has also naturalized in South Africa andSouth-Western Australia . Thespecies dispersed from the Mediterranean center to CentralEuropean countries, winning special recognition in Germanyand Poland. In Russia, narrow-leaved lupine becameknown only in the early 20th century.For thousands of years lupine has been used for greenmanure and animal feed. Before feeding the animals, lupineseeds were soaked in water, with several changes, in orderto remove alkaloids.The revolution in lupine breeding was observed in 1926\u20131928, when Reinhold von Sengbusch, a German botanist,discovered natural low-alkaloid mutants. It helped to reducethe alkaloid content in the seeds of L. albus, L. luteus andL. angustifolius from the traditional 1\u20133 % to 0.02 % andless . Since that time, the breeding oflow-alkaloid (sweet) lupine cultivars for animal feed hasbeen gaining progress. Initially, such cultivars emergedin Germany, then in Sweden, Denmark and Poland. Inthe USSR, the first natural low-alkaloid mutants weredevelopedby scientists at VIR and plant breeders of theNovozybkovand Minsk Experiment Stations . In Australia, where lupines were introduced inthe 1960s to improve crop rotations and reclaim sandy soils,the first sweet cultivar adapted to the local environmentswas released soon afterwards, in 1967, and large-scale lupine grain production started in 1973\u20131974 .Same as with most of the crops, the genetic diversity ofdomesticated narrow-leaved lupine forms is smaller thanthat of wild populations and landraces, and plant breedershave employed only a minor part of this diversity . Whole genome sequencing of 146 wildand 87 cultivated accessions from different genebanksover the world ascertained that the genomic diversity inmodern cultivars is thrice smaller than in wild populations . It should bementioned that 90 years that have passed since the development of the first low-alkaloid cultivars is quite a short timefor an agricultural crop, and the process of introducing thisspecies into cultivation cannot be regarded as finalized.http://reestr.gossortrf.ru/reestr.html).Russian breeding centers working with narrow-leavedlupine are the All-Russian Research Institute of Lupine,Nemchinovka Federal Research Center, Belogorka ResearchInstitute of Agriculture, Moscow Timiryazev AgriculturalAcademy, etc. Presently, there are 27 cultivarsof narrow-leaved lupine listed in the State Register forSelection Achievements Admitted for Usage . According to the standards acceptedby a number of European countries and Australia,the content of alkaloids in seeds intended to be used forfood or feed purposes (sweet) must not exceed 0.02 % oftheir dry weight . In Russia, fodder lupineseeds should have the percentage of alkaloids from 0.1 up to0.3 % of the seed dry weight ,and in those for human food their content is restricted to0.04 %, in line with the existing technical specificationsdeveloped at the All-Russian Research Institute of Lupine(TU-9716-004-0068502-2008).With the green biomass yield of 45\u201360 t/ha, lupine is able toaccumulate 100\u2013300 kg/ha of ecologically safe biologicalnitrogen in its biomass, which is comparable with animalmanure. Thus, the conditions are created for a stable orincreased supply of the soil with organic matter, so thatits physical and chemical properties improve, and thephytosanitary state of subsequent plantings is upgraded.Due to its deeply penetrating roots and high dissolvingcapacity of root excretions, lupine assimilates phosphorus,potassium, calcium, magnesium and other elements,contributing to their intensified circulation in the topsoiland subtopsoil horizons. On average, one hectare of lupineplants leaves to the next crop, in addition to nitrogen, 30 kgof phosphorus and 50 kg of potassium .The demand for narrow-leaved lupine as a green manureplant continues to grow. The yield of winter rye sown intogray forest soil on a green manure fallow after lupine,without fertilizers, increases by 0.5\u20131.0 t/ha . Besides, the alkaloids contained in the plowedgreen biomass produce a decontaminating effect on the soil,thus reducing the negative impact inflicted on subsequentcrops by their diseases and pests, such as various root rotsfor cereals or scab, Rhizoctonia rot and golden nematodefor potato . This phenomenon isundoubtedly interesting as a protective tool against fungaldisease agents, and calls for further research into themechanism of alkaloid activities . Hence, high alkaloid content becomesa preferable trait in green manure cultivars, which servesto simplify breeding schemes.Today, main requirements to lupine cultivars grown forgreen manure are high dry matter yield, rapid growth, andincreased nitrogen-fixing activity. The latest cultivars developedby Russian breeders \u2013 \u2018Oligarkh\u2019, \u2018Metsenat\u2019 and\u2018Akkord\u2019 (Belogorka Research Institute of Agriculture) \u2013contain 1.5 % of alkaloids in seeds and 0.7 % in the drymatter of green biomass, produce high yields of biomass(31\u201337 t/ha), demonstrate rapid initial growth and prolificfoliage, and are ready for plowing into the soil in the secondhalf of July, i. e., 50\u201360 days after sprout emergence.Lupine fodder is considered a good alternative to soybean:digestibility and feed energy coefficients of lupine proteinsare level with those of soybean and exceed those of pea,while the yield of lupine in the European part of Russia is1.5\u20132.0 times higher than soybean yield. Many Europeancountries do not produce soybean, so they are forced toexport it, mainly from South America, but the productionareas under lupine in Europe have good prospects forexpansion. According to the estimates by experts, the costprice of lupine grain production is twice lower than thatof soybean grain. Besides, narrow-leaved lupine produceshigher yields at lower energy costs than soybean: 840.7\u2013846.6 MJ/100 kg .The value of lupine as a fodder crop is all the more palpablein view of the fact that not only grain but also its greenbiomass, with 18\u201323 % of crude protein and up to 14 % ofsugar in dry matter, is readily consumed by all kinds of farmanimals. Lupine is used for feed as freshly cut plants, incrushed grain and compound feeds, as silage and haylage,as a component of cereal and legume haylage mixtures, etc.. Its green biomass is numberedamong highly nutritional succulent feeds, distinguished forits good digestibility and feed consumability. Lupine strawcontains up to 7 % of protein, which is the evidence of itshigher feeding value than the straw of cereal crops. It maybe added to silages made of the biomass of other crops. Lupineregrowth may be used for grazing, especially as far asswine and sheep are concerned. It is much more nourishingthan the stubble of cereals; it is even compared with grassylegume pastures. The practice of pasturing sheep and calveson harvested fields where grain and fodder lupine cultivarswere grown is widespread in Australia .It should be mentioned that the regrown lupine stubble isnot the only valuable grazing resource in a harvested field:leftover seeds are also a bonus \u2013 their losses at harvestingrange from 150 to 400 kg/ha .The lupine grain contains high enough amounts of tocopherol(3.9\u201316.2 mg%) and carotenoids (10\u201321 mg%),and 90 % of the latter is carotene. This is especially importantfor aquaculture, as many fish species cannot existwithout carotenoids .When eight crops were discussed in the context of theireligibility as major sources of plant protein for WesternEurope, considering their agronomic advantages, prospectsfor quick improvement, yield and quality of protein,technological aspects, functional and nutritional properties,lupine and pea were recognized as preferential over potato,triticale, alfalfa, etc. .Beginning from the late 20th century, lupine seeds havebeen widely used as ingredients by food industries ina number of European countries, Canada, the U.S., Chile,Australia, and to a much lesser extent in Russia and Belarus.Each year Europe consumes about 500,000 tons oflupine-containing food products, including lupine flour,lupine bran, lupine curd (tofu), etc. used as ingredients ofbread, pastry, pasta, dressings, milk substitutes, soybeansubstitutes in sausages, etc. Traditional for Southern Europeis a popular \u2018Lupini\u2019 snack, looking and tasting like popcornor cornflakes .Lupine products are regarded as functional food. Theycontain little fat and starch. Their glycemic index is low,which is taken into account by nutrition strategies to controlobesity, diabetes and cardiovascular diseases. Besides,they are gluten-free, which is important for celiac patients,so they are a valuable reserve to widen the range of foodstuffsfor this category of the population . Lupine proteins possessemulsifying and foaming capacities, which allow them tosubstitute butter and eggs in cookery . Lupine seeds are rich in ferritin, an iron-storingprotein .Besides, the grain of lupine owes its functional valuein human nutrition to dietary fibers whose content reach41.5 % . Favorableproperties to food products are rendered by lupineoil, with its well-balanced fatty acid composition and anoptimal ratio of omega-3 and omega-6 acids \u2013 from 1 : 1.7to 1 : 10.8 .Phenolic components and flavonoids in narrow-leavedlupine demonstrate antioxidant activity , reduce the risk of cardiovascular diseasesthrough their protective effect on blood vessels , and deter the development of some types of cancer,specifically the rectal cancer . Unlikesoybean, lupine contains small amounts of phytoestrogensand less antinutrients, such as phytic acid, oligosaccharides,trypsin inhibitors, lectins, tannins and saponins, than otherlegumes .Lupine seeds contain lutein and zeaxanthin \u2013 compoundsknown for their ability to hinder retinal degradation .The most popular lupine-based product with food industryis lupine flour. It is rich in lysine but poor in sulfurcontainingamino acids, such as methionine and cysteine,therefore it can serve as a good supplement to lysine-deficientwheat flour . Adding 10 % of lupine flour to bread, pasta or bakery products will notonly increase their functional value but also improve theirtexture, flavor and color, concurrently extending their shelflife .In Russia, technologies have been proposed to make pastasand fillings from lupine grain .Properties and effects of dietary fibers from lupine hullsare being studied in the context of their use as functionalingredients in some meat products, such as intermediateminced poultry meat , etc.Utilization of lupine for food purposes is growingworldwide.In Australia it is called the \u2018superfood\u2019 of the21st century. It is expected that in the nearest future majorinternational markets of nutriceutics will rise due to the onsetof chronic cardiovascular diseases, nervous disorders,and type 2 diabetes. A potentially huge market demandfor lupine-based products also exists among vegetarians,vegans, and people intolerant to gluten, soy, milk or eggsas well as in the growing sector of those who favor healthydiets .Composition, variability and toxicityAlkaloids are products of secondary metabolism. Unlikeprimary metabolites, their functional significance is not onthe level of a cell but on the level of a whole plant. Mostoften these compounds perform \u2018ecological\u2019 functions, i. e.,protect the plant from various pests and pathogens, ensureinteractions among plants and between plants and otherorganisms within an ecosystem, etc. .Different Lupinus species possess a unique alkaloid profile.Usually it consists of 4\u20135 major alkaloids and severalminor ones. The alkaloid composition of a plant is handyfor taxonomic purposes .Polymorphism of the narrow-leaved lupine gene poolin the content of alkaloids in seeds was uncovered byPolish researchers who studied 329 accessions from thelupine collection: 0.0005\u20132.8752 % .A common feature of all species is a high alkaloid contentin seeds (up to 4 %) and a lower content in green biomass(up to 1.5 %). In flowers up to 2.5 % is observed, while inroots their amount is minimal .Prevailing alkaloids in narrow-leaved lupine seeds arelupanine , angustifoline(10\u201315 %) and 13-hydroxylupanine (10\u201315 %).Minor levels are demonstrated by sparteine and lupinine. These values may vary dependingon the genotype and its locality. The concentration ofalkaloids in plant organs and their correlation can changeunder the effect of different growing conditions . Even in low-alkaloids cultivars their content isprone to variations within quite an extensive range, exceedingthreshold limit values .Lupines growing at high latitudes were found to contain lessalkaloids than those in southern areas .Accumulation of alkaloids in different plant organs is notsimultaneous. In the branching phase, when photosynthesisis especially active, the highest alkaloid content is observedin leaves. In the flowering phase, an intensive efflux ofalkaloids occurs from the vegetative organs of a plantto the generative ones, where their content reaches theirmaximum by the beginning of pod maturation. Each phaseof plant development is characterized by its own qualitativecomposition of secondary metabolites, including alkaloids.Hydroxylupanine dominates at the start of branching, andlupanine at the time of flowering and pod maturation. Bythe seed ripening period, the alkaloid content in seeds is5\u201310 times higher than in green biomass . Sparteine and lupanine are the most toxic, followedin descending order by lupinine, hydroxylupanine andangustifoline .Interestingly enough, when a plant has been mechanicallyinjured, the amount of alkaloids in it grows fourfold.The injury, in this case, mimics the bite of an insect, whichmay serve as an evidence of the protective functions performedby alkaloids. With this in view, lupanine inflictsthe strongest toxic effect on sucking insects .Metabolomic profiling may prove an effective approachto the assessment of alkaloid biosynthesis activity in thespecies\u2019 gene pool and the impact of diverse abiotic andbiotic environmental factors on this process. Studying metabolomicprofiles in wild lupine forms will help to identifyor specify the role of individual alkaloids in the species\u2019adaptation to changing environmental conditions .Practical importance of narrow-leaved lupine alkaloidsSince long ago alkaloids have been extensively applied inmedicine, pharmacology, veterinary and other sectors. Inthe first place, they are used as effective agents in pharmaceuticalsto provide complex treatment of many dangerousdiseases, cancer included . They prevent the onset of various degenerativepathologies, binding free radicals and metal ions thatactivate enzymes of oxidative reactions. They also inhibitthe growth and development of fungi, protozoa, bacteria,etc. .Sparteine has the widest application. It decreases thelevel of glucose in an organism and initiates insulin secretion, exerts a mild analgesic effect,and acts as an anticonvulsant and antiepileptic . Together with lupanine andhydroxylupanine, it is included in the composition of antiarrhythmicdrugs. Such antiarrhythmic effect weakens in thedescending order of sparteine\u2013lupanine\u2013hydroxylupanine. Among the Class IA medicamentsagainst tachyarrhythmia there is a combined drug, knownas Pulsonorma, which incorporates in its compositionajmaline,sparteine, antazoline and phenobarbital .Lupanine is a very active neurotransmitter for nAChR(nicotinic acetylcholine receptors) which play a decisiverole in neuron signal transmission. The data were obtainedon its ability to increase insulin secretion . It may be used as source material for the synthesisof other alkaloids which are very difficult to produceartificially .Angustifoline on the cell culture of a malignant tumor inthe human large intestine (line COLO-205) induced autophagyin tumor cells, apoptosis processes and interruptionof the cell cycle in the G2/M stage, so it may be regardedas an antineoplastic agent .Lupinine demonstrates moderate antiglycation activity,without any cytotoxic effect . It is alsocharacterized by strong insecticidal activity .Allelopathic effects of lupine alkaloids are confirmedagain and again , for example, by their antimicrobialactivity in the culture of Staphylococcus aureus,Escherichia coli, Pseudomonas aeruginosa Mig., Bacillussubtilis Cohn., Klebsiella pneumoniae Trevis., in concentrations3\u20134 orders lower than that of antibiotics .An in vivo trial on lupine-fed goats showed moderatebut credible activity of a lupine seed extract against thenematodes Haemonchus contortus and Teladorsagia circumcincta.There is a lot of evidence to the antifungal effect of alkaloids.Fusarium resistance of high-alkaloid lupine cultivarswas shown to be higher than that in low-alkaloid ones, and an increased alkaloid content in plant cells was reportedin response to the infection by causative agents. Purifiedlupine alkaloids may be used for pre-sowing treatment oflegume crop seeds to raise their resistance to anthracnose,Fusarium, and other fungal diseases. The advantage ofalkaloids over synthetic fungicides is their biodegradationand lesser toxicity .There are five known genes reducing alkaloid content innarrow-leaved lupine seeds: iuc (iucundus), es (esculentus), dep (depressus) , a1, a2, a3 (angustifolius) , andtant . The iuc gene determinesa reduction in alkaloid concentration approximately to0.06 % dry weight, dep is responsible for very low contentof alkaloids (ca. 0.01 %), while es governs their intermediateconcentration . Each stage inthe synthesis of alkaloids is controlled by certain alleles,capable of independent mutations and recombinations.Non-allelic mutations are possible: they have a similarphenotypic effect, leading to a low content or absence ofalkaloids . The discovery of complementarygene interactions made it possible to produce the firstabsolutely alkaloid-free forms by uniting the genes of twonon-allelic recessive mutants in one genotype . Thus, the absence or low content of alkaloids isa complex quantitative trait of polygenic nature with freecomplementation between its non-allelic complementarygenes , which is a serious obstacle forthe crop\u2019s breeding and seed production.It was observed in the process of breeding sweet cultivarsof narrow-leaved lupine that they were considerablyless resistant to diseases and pests than bitter ones: theirsusceptibility to insect attacks increased as well as, accordingly,vulnerability to virus diseases carried by, forexample, aphids .The end of the 20th century was marked by drastic onsetsof Fusarium and anthracnose in all countries producingnarrow-leaved lupine. The idea emerged to develop \u2018bitter/sweet\u2019 cultivars, combining the bitterness of green biomassas a means of defense against pests and low alkaloid contentin seeds to make them usable as feed or food . Such idea could not be implementedwithout the knowledge of the entire multistep way ofalkaloid biosynthesis which starts within the chloroplastsof young lupine leaves , from where they are transported through thephloem into the generative organs . Recentresearch on the expression of genes responsible foralkaloid biosynthesis has shown that such biosynthesis iscompletely or nearly absent in the seeds, which confirms thetransport of alkaloids from other tissues .Biosynthesis of quinolizidine alkaloids has been studiedto a much lesser extent than that of some economically important alkaloids in other plants that represent the modelspecies for better understanding of this process . That is why theattempts have been made to gain an insight into the waysof lupine alkaloid synthesis and transport, using the knowledgeof the synthesis of other alkaloids and the searchesfor homologous genes .Along with approaching these breeding tasks, whichprospectively can be solved through the use of new reversebreeding or genome editing technologies, they are tryingto modernize the centuries-old experience in the removalof bitterness from lupine seeds and green biomass. Theydevelop the techniques of alkaloid extraction from largeamounts of raw plant produce yielded by bitter cultivars,thus making it fit for animal feed. In 2013, for example,Russian researchers developed and patented the cost-effectivebiotechnology of profound lupine grain processingin a milk serum medium. Such line may be installed intothe technological process of any compound feed producingfactory . Thermal seedtreatment with alkaline solutions could reduce alkaloidconcentrations in seeds to 0.003 % . In Portugal, at the enterprises that extractalkaloids from large bulks of lupine and consume lots ofwater, a trial was conducted to test the technology of dischargedwater detoxification by nanofiltration and bindingof 99 % of lupanine contained in it, so that the latter couldbe used as raw material for the pharmaceutical industry.Thus, at present there are two ways to obtain alkaloidfreeraw produce of narrow-leaved lupine for food andfeed purposes: lengthy and intricate development oflow-alkaloid cultivars by conventional breeding techniques,and novel technological lines of alkaloid removal/extraction. The solution for lupine breeding is seen in thegenome-based biotechnologies, as their certain prospectsfor narrow-leaved lupine are quite obvious.Intensification of breeding practice requires rich and diversesource material. A number of the world\u2019s genebanksmaintain the global diversity of L. angustifolius. The largestcollections are in Australia, Poland, Portugal, and theRussian Federation. The Australian collection includesmostly wild lupine forms, recombinant inbred lines, mutantpopulations, and interspecies hybrids. These resources areused to study the genetic and molecular control over thekey traits, and this work is expected to be reinforced by theongoing research into L. angustifolius genome sequencing.The main objective of Australian researchers is to expandthe genetic base of the species, including the involvementof wild lupine forms. Marker-based introgressionof the desired traits is proposed . Themarker-assisted selection has already become an integral element of Australian breeding programs and acceleratedthe development of new cultivars .Genetic maps have been produced for narrow-leavedlupine as wellas vast libraries of genomic insertions .Genes responsible for the expression of economically usefultraits, alkaloid content included, have been discoveredand mapped .The only one recessive iuc gene, out of the five knownones that determine the alkaloid content in narrow-leavedlupine, is used in breeding programs. The gene\u2019s molecularfunctions have not yet been identified. Markers havebeen found for the locus iuc, and the denser cartographicresources and genome annotation have narrowed the regionof the iucundus candidate gene . The NGS (next generation sequence) technology isapplied for more rapid development of markers for breeding.The paths of alkaloid synthesis are partially known.However, their genetic base still remains poorly studied.Transcriptome sequencing (RNA-seq) and analysis ofdifferentially expressed genes in a sample containing bitterand sweet narrow-leaved lupine accessions helped todetect 13 genes presumably involved in the synthesis ofquinolizidine alkaloids . The identifiedalkaloid biosynthesis genes were mapped, but onlyone transcriptomic factor from the RAP2 family of factorsregulating secondary metabolism was closely linked withthe iuc gene . Investigating the mappingpopulations with the technique of massive analysisfor cDNA ends (MACE) confirmed the idea that theETHYLENE-RESPONSIVE TRANSCRIPTION RAC2-7gene factor could control the low-alkaloid phenotype innarrow-leaved lupine .The gene pool of narrow-leaved lupine should becomethe target of more intense research on the phenotypicand genotypic levels, so that its diversity would be moreobvious and available to plant breeders. This will help tooptimize the development of cultivars with the desiredproperties. With this in view, it seems rational to makegreen manure cultivars high-alkaloid, but those intendedfor food and feed must not lose their adaptability-relatedtraits, including pathogen resistance, at the expense ofeliminated alkaloids. In this regard, a productive idea is toproduce \u2018bitter/sweet\u2019 cultivars, combining high alkaloidcontent in their green biomass with a low alkaloid levelin seeds. Its implementation depends on the knowledgeof alkaloid biosynthesis and transport pathways in a plantand the possibility of their regulation, which seems a taskfor the nearest future, considering the currently availablegenomic resources. However, at the present moment it isnot expedient to discard routine technologies of raw plantproduce processing, using alkaloid extraction techniqueswith concurrent isolation of valuable ingredients for thepharmaceutical industry. Genetic resources\u2013phenotyping-metabolomics\u2013conventional breeding practice; genomicresources\u2013marker-assisted and genomic selection/genome editing; and cost-effective technologies of alkaloidextraction from the raw produce of bitter cultivars \u2013 theseapproaches are, in our opinion, the best to improve theeconomic potential of this valuable pulse crop and makeuse of it in the present-day situation and in future.The authors declare no conflict of interest.Abbas G., Al-Harrasi A.S., Hussain H., Sattar S.A., Choudhary M.I.Identification of natural products and their derivatives as promisinginhibitors of protein glycation with non-toxic nature againstmouse fibroblast 3T3 cells. Int. J. Phytomed. 2017;8(4):533-539.DOI 10.5138/09750185.1924.Adhikari K.N., Edwards O.R., Wang S., Ridsdill-Smith T.J., BuirchellB. The role of alkaloids in conferring aphid resistance inyellow lupin (Lupinus luteus L.). Crop Pasture Sci. 2012;63:444-451. 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The creation of new Lathyrus L. sorts with an improved nutrient composition of nutrientswill allow to obtain high-quality feed in areas with extremely unstable weather conditions. In this connection, westudied the patterns of variability in the parameters of the carbohydrate complex , polyols , phytosterols, free fatty acids (FFA) and acylglycerols in thegreen mass of 32 samples of Lathyrus sativus L., L. tuberosus L., L. sylvestris L., L. vernus (L.) Bernh., L. latifolius L.,L. linifolius (Reichard) Bassler. from the VIR collection, reproduced in the Leningrad region in contrasting conditions2012, 2013.The content of identified compounds varied depending on the genotype, species, and weatherconditions. High temperatures and high level of precipitation in 2013 contributed to the accumulation of monosaccharides,in more colder and drier conditions in 2012 \u2013 oligosaccharides, most of polyols and FFA. The cultivatedspecies (L. sativus) was distinguished by its high sugar content, and the wild species as follows: L. latifolius by FFA;L. linifolius by ononitol, myo-inositol, and glycerol 3-phosphate; L. vernus by MAG and methylpentofuranoside. Thespecies cultivated in culture (L. sativus) was distinguished by a high sugar content, wild species: L. latifolius \u2013 by FFA,L. linifolius \u2013 ononitol, myo-inositol and glycerol-3-phosphate, L. vernus \u2013 MAG and methylpentofuranoside. Accordingto our results, the studied samples are promising for the selection of Lathyrus varieties with high nutritionquality and stress-resistant. The changing climate leads to the expansion of areas withextremely unstable weather conditions, thus enhancing thedemand for stress-resistant crops grown for food and feed.Many species in the genus Lathyrus L. are used as sourcesof human food, animal feed, and medications. A majority ofwild peavines are exploited as pasture and fodder plants. Thebest-known species is the grass pea (Lathyrus sativus L.)with its millennia-long cultivation history, cultivated on allthe continents. This leguminous crop is considered one of themost resistant to drought, waterlogging, and cold . It is adapted to a diversity of soil types, includingsalinized soils, and would yield harvests in the environmentswhere other crops would die, so it was recognized as \u2018the foodfor survival\u2019 . The species is resistant todiseases and pests . The yield of grass pea seed reaches 2.9 t/ha, and thatof its green biomass is 5.2 t/ha.Grass pea seed and green biomass are notable for their highnutritional value. The grain contains, depending on growingconditions, from 18 to 34 % of protein , and the biomassfrom 10 to 27 % . Seeds of L. sativusand L. cicera L. are characterized by high concentrationsof essential amino acids (63\u201364 %) and polyunsaturatedfatty acids , predominantlylinoleic . The hay from grass pea matchesalfalfa in nutritiousness . The contentof organic acids in the Lathyrus green biomass varies from140.0 to 2140.0 mg/100 g, free amino acids from 11.8 to610.0 mg/100 g, and secondary metabolites from 4.4 to224.6 mg/100 g .In Russia, compared with other countries, Lathyrus spp. occupya minor niche in the national plant production. Breedingwork is conducted in a limited number of institutions, whichhas a negative effect on the crop\u2019s utilization in agriculture.Our previous investigations of the green biomass of wildand cultivated Lathyrus spp. exposed a wide range of compoundsin it . Accessions from the peavine collection wereidentified as promising sources for the development of highlynutritious, resistant and officinal cultivars .The present study is the next step in the research into metabolomicprofiles of peavine green biomass with a focus onthe content of saccharides, free fatty acids (FFA), polyols, andacylglycerols. The objective of the study was to assess theinterspecific and intraspecific polymorphisms of biochemicalcharacters in Lathyrus spp. and the effect of weather conditionson their variability. To solve this task, the technique currently widely known as profiling was used . This technique is one of the so-called metabolomicmethods of analysis, which, in addition to delivering informationon individual metabolites in a studied object, makes itpossible to evaluate the status of this object .Thus, our aim was gaining knowledge about variations inthe status of metabolic networks in the accessions of Lathyrusspp. in the context of their taxonomic characteristics andweather conditions.The experiment encompassed 32 accessions of six Lathyrusspp. from the collection of the Vavilov Institute (VIR):grass pea (L. sativus), flat pea (L. sylvestris L.), spring pea(L. vernus (L.) Bernh.), heath pea (L. linifolius (Reichard)Bassler), everlasting pea (L. latifolius L.), and tuberous pea(L. tuberosus L.), grown in the fields of Pushkin experimentallaboratories of VIR in 2012 and 2013 according tothe guidelines approved by VIR .Meteorological conditions during the growing seasons werecontrasting. In 2012, the sum of active temperatures was1885.0 \u00b0\u0421, and the precipitation amount 340.7 mm; in 2013,the sum of active temperatures increased to 2474.3 \u00b0\u0421, andrainfall to 646.4 mm.Plants were collected in the phase of first mature pods. Freshgreen biomass was analyzed from 5 plants of each accession. Gas chromatography/mass spectrometry (GC\u2013MS)profiling was performed using the protocol for the analysisof trimethylsilyl derivatives, developed at the Komarov BotanicalInstitute while working on the program task, theme\u0410\u0410\u0410\u0410-\u041018-118032390136-5 \u201cAssessment of changes in thecorrelational structure of metabolite networks in the processof growth and development of fungi and plants from theviewpoint of systemic biology\u201d, and adjusted for use on Agilent6850-MSD 5975 at the Research Park of St. PetersburgState University Center for Molecular and Cell Technologies.The plant material was examined by the GC\u2013MS technique:it was extracted with ethanol, and then evaporated dryon a CentriVap Concentrator . The solidresidue was dissolved in pyridine containing 1000 ppm oftricosane that served as an internal standard; then, 20 \u03bcl ofBSTFA was introduced. To ensure the silylation reaction sufficiency,the vials were kept for 15 min under +100 \u00b0\u0421 ina special thermal block. The samples were analyzed on anAgilent 6850 chromatographic mass spectrometer with theAgilent 5975 D mass selective detector (USA). Chromatographic separation was done on an Agilent HP-5MS column(USA), length: 30 m, internal diameter: 0.25 mm, stationaryphase film thickness:0.25 \u03bcm, linear temperature programmingmode: 70 to 325 \u00b0C, speed: 6\u00b0/min (50 min), carrier gas:helium. The analysis was performed with a constant gas flowvelocity through the column (1 mL/min) as follows: evaporatortemperature: +300 \u00b0\u0421; flow split ratio during sample injection:1: 20; mass spectra scanning range: 50 to 1050 amu; scanningspeed: 2 scans/sec. Total ion current (TIC) chromatogramswere recorded for the samples.The results were processed using UniChrom and AMDISsoftware resources, NIST 2010 mass spectra libraries, andin-house libraries of the Research Park of St. Petersburg StateUniversity and the Komarov Botanical Institute.The amount of trimethylsilyl (TMS) derivatives of theidentified compounds was calculated by the internal standardizationmethod for tricosane using UniChrom software. Withthe semiquantitation approach applied, the detector\u2019s sensitivitycoefficients for individual compounds need not be takeninto account . The data produced bythe analysis are presented in conventional units (c. u.) .2 \u2013 was calculated by the following formula :Statistical data processing was done with Statistica 7 andEx\u0441el 7.0 software for Windows, using the principal factoranalysis (PFA) and one-way analysis of variance (ANOVA).Statistical significance of the environmental effect on theexpression of biochemical characters was assessed usingFisher\u2019s criterion (LSD test), and the factor\u2019s effect size (percentage)\u2013 \u03b72, % is the effect size percentage of the factor\u2019s impact;SSfactor is the sum of squared deviations for the factor; SStotalis the total sum of squared deviations.where \u03b71.The GC\u2013MS profiling of the green biomass of Lathyrus L. spp.identified about 300 components. Organic acids, free aminoacids and phenol-containing compounds were discussed inan earlier publication . This studypresents analytical results of comparing the contents of over60 compounds in the peavine green biomass, including suchgroups as sugars, polyols, phytosterols, and FFA. The levels ofthe identified compounds are presented in c. u. http://www.bionet.nsc.ru/vogis/download/pict-2020-24/appx11.pdfSupplementary Materials are available in the online version of the paper:Carbohydrate composition. Sugars in the peavine greenbiomass consisted of mono- and oligosaccharides. Monosaccharideswere represented by pentoses and hexoses . Oligosaccharidesincluded disaccharides and atrisaccharide (raffinose). Fructose, glucose and mannose werethe main sugars in the hexose group, xylose in the pentosegroup, and sucrose in the group of disaccharides . Besides,metabolically active forms of saccharides were idenified: lactone , phosphate (fructose 6-phosphateand glucose 1-phosphate), and methyl sugars (methylpentofuranosideand methylglucofuranoside).The relative content of sugars varied across the years and the genotypes. A majority of sugars were monosaccharides represented mostly byhexoses . Pentoses amounted toslightly more than 1 %, and oligosaccharides to 32.6 %; of thelatter, disaccharides accounted for 32.3 %, and trisaccharidesfor 0.3 %. Sucrose had the highest percentage among disaccharides(31.9 %).The mean value for sugars in 2012 was 1442 c. u. (40 to4470). The greatest part of sugars was represented by disaccharides,their mean content equal to 903 c. u. (0 to 3983).The mean total amount of monosaccharides was 538 c. u. (40to 2085). They were represented mostly by hexoses, with themean level of 530 c. u. (29 to 2082). Pentoses averaged 8 c. u.(0 to 24). Identified among trisaccharides was raffinose whosemean content was 1 c. u. (0 to 14). The mean content of totaloligosaccharides was 904 c. u. (0 to 3984).In 2012, the highest saccharide levels were recorded forthe accessions of L. sativus (up to 4470 c. u.) and L. sylvestris(up to 1162). The remaining peavine species accumulated lessthan 600 c. u. of sugars. The lowest values were observed inthe accessions of L. tuberosus (144 c. u.).In 2013, the total content of sugars, including monosaccharides(hexoses and pentoses), increased on average to1830 and 1278 c. u., respectively, while the content of sucrosereduced to 551. Compared with 2012, the limits of the variationrange changed for total sugars from 144 to 2511 c. u., formonosaccharides from 63 to 1842 c. u. (for hexoses from 63to 1751 c. u.), and for oligosaccharides from 273 to 1060 c. u.The major part of sugars in 2013 was represented by monosaccharides(hexoses). Mean values for total oligosaccharides in2013 decreased to 532 c. u., while those for raffinose increasedto 11 c. u. The ranges of variability for pentoses and raffinose in 2013 became widerthan in the previous year.High levels of sugars (more than 2831 c. u.) during theentire period of studies were observed in the accessions ofL. sativus.Polyols and phytosterols. Most of the identified polyolswere hexatomic ; theirmean total amount was 476 c. u. . Theywere represented mainly by inositol, its isomers and derivatives; their total sum was 413 u. e. In addition to thealcohols mentioned above, glycerol, erythritol, threitol, xylitol,arabinitol and phytol were identified. Besides, phytosterols and phenolic alcohols were observed; their total sumswere 9 and 3 c. u., respectively. In the phytosterol group, \u03b2-sitosterolprevailed (8 c. u.). Phosphate forms of glycerol andinositol were also identified as well as metabolic products ofglycerophospholipids (glycerol 3-phosphate and myo-inositol2-phosphate). Phenol-containing alcohols were discussedearlier .The content of polyols significantly varied across theyears of the study . In 2012, their mean levelwas 744 c. u., with the limits of variation from 171 to 3184.In 2013, their amount reduced to 317 c. u., and the range oftheir variation narrowed (77 to 442). This value in L. sativusin 2012 (637 c. u.) was lower than the mean , but in 2013 it decreased to 322 c. u. The sametendency was observed in the accessions of L. sylvestris:437 c. u. in 2012, and 275 c. u. in 2013.The highest content of polyols was found in L. sativus(3152 c. u.), a lower one in the accessions L. linifolius (2307),L. vernus (1050), L. sylvestris (619) and L. latifolius (348),and the lowest in L. tuberosus (66).The highest amounts of erythritol and phytosterols were observed in the accessions of L. sativus,and the highest total polyols in L. sativus and L. linifolius.Free fatty acids and acylglycerols. Nineteen FFA wereidentified, including saturated and unsaturated ones ,hydroxy acids ,and monoacylglycerols (MAG-1 C16:0and MAG-1 C18:0) .In 2012, the total FFA content in the peavine green biomasswas 248 c. u. (limits of variation from 37 to 732), with 1 c. u.for MAG (0 to 21). In 2013, the values of FFA and MAG reducedto 52 and 0.5 c. u., and their variation limits narrowed .Hydroxyhexacosanoic, palmitic, linolenic and stearic acidsshowed the highest values: their shares in the total content ofFFA and hydroxy acids were 32, 22, 14 and 13 %, respectively.The mean percentage of linoleic acids was 7 %, with 5 % ofcapric, 3 % of oleic, 2 % of hydroxyoctacosanoic, and 1 %of undecylic acid. The percentage of minor FFA was lessthan 1 %.The highest mean content of FFA was observed in the accessionsof L. latifolius (up to 345 c. u.). Other species showedlower levels: 162 c. u. in L. sativus, 131 in L. sylvestris, 114 inL. linifolius, and 86 in L. tuberosus. The lowest FFA amountswere found in L. vernus (50 c. u.), but this species was distinguishedfor the contents of MAG-1 C16:0 (up to 11 c. u.)and MAG-1 C18:0 (up to 10). The levels of MAG in the otherspecies were much lower.Our experiment disclosed the presence of significant interspecificand intraspecific variability of the Lathyrus accessionsboth in the quantitative content and qualitative compositionof the identified compounds .The analysis of the resulting data showed a strong variationin the values under different weather conditions .High temperatures and intense rainfall (2013) contributed to the accumulation of sugars at the expense of an increasein the percentage of monosaccharides, while the colder anddrier conditions (2012) provoked a rise of polyols, FFA andoligosaccharides.A single factor analysis of variance was applied to ascertainthe statistical significance of the effect of weather on thestudied characters. Growing conditions were found to producea statistically significant impact on the variability ofthe total sugars, total FFA, ribose, arabinose, xylose, altrose,rhamnose, mannose, glucose, galactose, sucrose, maltose,rutinose, raffinose, certain acids ,stigmasterol, threitol, glycerol, xylitol,erythritol, ononitol, sorbitol, mannitol, phytol, \u03b2-sitosterol,campesterol, phosphate, glucose 1-phosphate, methylphosphate,threono-1,4-lactone, and glucono-1,4-lactone . Variations of other compounds were notsignificantly affected by weather. The strongest effect of growingconditions was observed in the accumulation of mannose(effect size \u03b72 = 62.9 %), rhamnose (62.3), glucose (56.7),raffinose (41.1) and altrose (40.9 %) in the peavine biomass.Variability of the total FFA levels was determined by meteorologicalconditions to the extent of 34.1 %; linolenic (51.1)and palmitic (46.9) acids were the most dependent on them.Among phytosterols, the highest values of \u03b72 were recordedfor campesterol (80.2 %) and stigmasterol (71.6); amongpolyols, for threitol (53.6 %) and mannitol (37.9). A significantweather impact was produced on the content of phosphoricacid derivatives (60.0 %), glucose 1-phosphate (36.7), andthreono-1,4-lactone (31.5). Thus, weather conditions werefound to have a significant effect on the accumulation ofa considerable number of identified compounds in the greenbiomass of Lathyrus spp.The principal factor analysis (PFA) was applied to revealthe interplay among biochemical characters and disclose regularitiesin their variations under the influence of weatherconditions, genotypes, and taxonomic (species-specific) attribution.As a result, 10 factors determining 65.8 % of thetotal variance in plant characters were identified. In the firstfactor , two large groups ofbiochemical characters demonstrated negatively correlatedconcurrent variations. The first group included rhamnose,xylose, altrose, glucose, maltose, rutinose, raffinose, erythritol,threitol, mannitol, campesterol, stigmasterol, phosphate andglucose 1-phosphate; the second one united palmitic, linoleic,linolenic and stearic acids, glycerol, sorbitol, \u03b2-sitosterol andthreono-1,4-lactone. This factor demonstrates that higheramounts of the compounds from the first group in peavinegreen biomass are accompanied by lower levels of those fromthe second group, and vice versa. The dominating charactersin F1 (determining variations of the others) are campesterol,stigmasterol, linolenic acid, and palmitic acid. The secondfactor proves the relationship between sorbose andfructose. The third ascertains the interactions ofmethyl-inositol, glyceraldehide, \u03b1-methylglucofuranoside, andmethylglucoside. The fourth shows correlationsbetween capric, oleic and hydroxytetracosanoic acids. Thefifth incorporates arachidic, behenic, hydroxyhexacosanoicand hydroxyoctacosanoic acids. The sixth factor includes melissic and hydroxyoctadecanoic acids, the seventh ononitol, the eighth glycerol 3-phosphate, the ninth lupeol and guanosine,and the tenth myo-inositol 2-phosphateand uridine.While studying the distribution of accessions in the spaceof the first two factors, it seems obvious that the plants aregrouped according to the years of observations . Theright-hand part of the graph contains cultivars with high levels of saccharides , phosphate,erythritol,threitol, mannitol, campesterol and stigmasterol,and low levels of FFA , glycerol, sorbitol, \u03b2-sitosterol, threono-1,4-lactone.The left-hand part harbors accessions with the opposite valuesof the above-listed compounds, the upper part with minimalamounts of sorbose and fructose, and the bottom part withthe highest levels of these two sugars. Thus, the accessionsreproduced in 2013 clustered in the section with high amountsof most of the sugars, while those of 2012 in the FFA section.Adverse growing condition (2012) provoked the accumulationof glycerol, sorbitol and \u03b2-sitosterol, whereas optimal conditionsfor plant growth and development (2013) favored erythritol,threitol, mannitol, campesterol and stigmasterol. Thewild species L. vernus, L. linifolius and L. tuberosus showedintermediate levels of most sugars, polyols and FFA, and lowvalues of fructose and sorbose. The accessions of L. sylvestrisdiffered from other wild forms in the higher fructose and sorbosecontent. Many indicators in L. latifolius were close tothose in L. sylvestris. The cultivated L. sativus demonstratedthe richest polymorphism of all the studied characters. Mostof the cultivars representing L. sativus concentrated in the sectionof intermediate and high levels of fructose and sorbose,but no species-specific groups were observed for the otherbiochemical characters: the accessions scattered across thegraph in accordance with individual features of their genotypesand their normal responses to weather conditions.Factors F3\u2013F10 highlighted heterogeneity of the accessionsin each of the principal components . Maximumsof factor loadings for most of the factors were recordedin the accessions of L. sativus (k-34 and k-900), L. linifolius(N-597422), and L. vernus (N-591179 and N-593953).According to Chavan (1998), the green biomass of peavinesis characterized by a fairy high content of sugars. Within theplant, sugars play the role of osmoprotectants and stabilizers ofmembranes and proteins, including the same under the impactof low temperatures. Therefore, accessions with high sugarcontent, especially as far as oligosaccharides and raffinoseare concerned, are more resistant to abiotic environmentalstressors.Oligosaccharides are accumulated by a plant as a responseto the cold stress . In our experiment, the growth of the oligosaccharidecontent was observed in the year with lower temperatures,which confirmed the above-mentioned. The highest levels ofraffinose were observed in L. sativus, so its accessions maybe recommended to breeders to develop stress-adaptable andcold-tolerant cultivars.Some researchers reported that if the raffinose content infood or feed exceeded 0.4 % dry weight it may cause dyspepticdisorders . In our experiment, itspercentage never exceeded this level, so the green biomassof all studied peavine species may be used as animal feed.Mannitol, arabinitol, sorbitol, galactinol, dulcitol, erythritoland other polyols improve adaptive properties of a plantagainst salt, water and temperature stresses. Accessions witha high content of these compounds may be identified aspotentially resistant to unfavorable environmental factors. According to our data, thecontent of glycerol and sorbitol in peavine green biomass washigher under cold and dry conditions in 2012 , which confirmed the results of the authorsreferred to above. The highest levels of glycerol and sorbitolwere observed in L. sativus.Inositol, its isomers and derivatives, including phosphateones participate in the cell membranebiosynthesis and plant growth regulation, are incorporatedinto the composition of the cell\u2019s phosphate \u2018depot\u2019,and appear among the antistress factors of plant protection(osmolites) . In this research, when theplants developed under cold dry conditions, their mean valuesof ononitol were higher than in an optimal environment . The same situation was observedwith the levels of mannitol, xylitol and erythritol in the greenbiomass of L. sativus: under unfavorable conditions theircontent increased. The maximums of methyl-inositol, chiroinositol,and myo-inositol 2-phosphate were identified in L. sativus, while myo-inositoland ononitol maximums in L. linifolius . On the whole, high values in the polyol contentwere recorded for all Lathyrus spp., which explains theirresistance to abiotic and biotic stressors.Phytosterols play an important role in plant growth anddevelopment, because they are precursors of phytohormones. According to published data, the main phytosterolin plants is \u03b2-sitosterol, which coincides with our results:\u03b2-sitosterol accounted for 86.5 % of the total content of identifiedsterols. In our experiment, the total phytosterol contentin the peavine biomass was 39 c. u.Among FFA on the surface of L. sativus seeds, palmitoleicand palmitic acids are prevailing, followed in descendingorder by stearic, myristic, oleic, arachidic, capric, behenic,linoleic and linolenic acids . In this study, the major share of identified FFA also went to palmitic,linoleic, linolenic, oleic and stearic acids. The presenceof the mentioned FFA in green biomass characterizespeavines as highly nutritional fodder plants promising forcultivation.Thus, over 300 compounds have been identified in the greenbiomass of Lathyrus spp. ; more than60 of them are described in this publication. The values ofa majority of the analyzed biochemical substances demonstrateda wide range of variability. Their amounts significantlyvaried across different genotypes, species, and years of testing.The studied accessions showed high intra- and interspecificpolymorphisms, both in the quantitative content and qualitativecomposition of the identified compounds.Wild species hadmedium values in the content of most sugars, polyols and FFA,and low levels of fructose and sorbose. As far as their sugarcontent is concerned, L. sylvestris and L. latifolius occupiedan intermediate position between the abovementioned wildspecies and L. sativus. The cultivated L. sativus stood out forthe highest amount of sugars in its green biomass, L. linifoliusfor ononitol, myo-inositol and glycerol 3-phosphate, whileL. vernus for MAG and methylpentofuranoside.The comparative analysis helped to identify accessions suitablefor further profound investigations into sugars, polyols,FFA, phytosterols, etc. It is especially valuable for futureresearching, because these compounds are indicators of greenbiomass quality and resistance to unfavorable environmentalfactors. The identified accessions can be used to produceboth highly nutritional and resistant cultivars of Lathyrusspp. Considering the latest achievements in genomics, suchaccessions may be regarded as quality and resistance sourcesnot only for peavines but for other crops as well.Considerable polymorphism of biochemical characters hasbeen disclosed in wild and cultivated Lathyrus spp. Theresults obtained attest to the high potential of the studiedspecies for contemporary agricultural production and newbreeding trends.Introducing L. sativus, L. sylvestris, L. vernus, L. linifolius,L. latifolius and L. tuberosus into animal feed productionwould expand the assortment of the exploited fodder crops.Due to their resistance to abiotic stressors and the disclosednutritional value, Lathyrus spp. could play an important rolein food security maintenance in areas with unpredictableweather conditions.The authors declare no conflict of interest.Adhikary P., Mukherjee A., Barik A. 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Multivariate analysis in metabolomics. Curr. Metabolomics.2012;1(1):92-107. DOI 10.2174/2213235X11301010092.Zhou J., Yang Y., Yu J., Wang L., Yu X., Ohtani M., Kusano M., Saito K.,Demura T., Zhuge Q. Responses of Populus trichocarpa galactinolsynthase genes to abiotic stresses. J. Plant Res. 2014;127(2):347-358. DOI 10.1007/s10265-013-0597-8."} +{"text": "Research is an essential component of Anesthesia, and the contributions of researchers and institutions can be appreciated from the analysis of scholarly outputs. Such analyses help identify major contributors and trends in publication. Little is known about the state of Anesthesia and Critical Care Medicine (A.C.C.M.) research in Africa. We aimed to describe African A.C.C.M. research\u2019s current landscape by determining its productivity per country and point towards possible ideas for improvement.P-value <\u20090.05 was considered statistically significant.The authors searched PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to May 4, 2020, for articles on or about A.C.C.M. in Africa. Studies were selected based on their titles and abstracts. Rayyan software was later on used for data management in the review selection process. Then, the full-text of eligible articles were screened. Data were extracted, and the number of articles per physician anesthesia providers and provider density were calculated. Kruskal Wallis test and Spearman\u2019s correlation were used, and a Of the 4690 articles, only 886 (18.9%) were included in the analysis. The articles were published between 1946 and 2020 in 278 target journals. 55 (6.2%) articles were published in the South African Journal of Surgery, 51 (5.8%) in Anesthesia and Analgesia, and 46 (5.2%) in Anaesthesia. 291 (32.8%) studies were cross-sectional. 195 (22.0%) first authors were from Nigeria, 118 (13.3%) from South Africa, and 88 (9.9%) from the U.S.A. Malawi (1.67), Togo (1.06), and Sierra Leone (1.00) had the highest number of articles per provider. Whereas Ethiopia (580.00), Nigeria (336.21), and Malawi (333.33) had the highest number of articles per provider density.We identified the most and least productive African countries in A.C.C.M. research and a low-quality hierarchy of evidence in these publications. Hence, the study\u2019s findings may aid in driving the A.C.C.M. research agenda and capacity building in Africa. African anesthesia and critical care medicine (A.C.C.M.) face numerous challenges: delayed patient presentations, lack of equipment, lack of an adequate specialist workforce, poor information management infrastructure, and lack of funding \u20133. TheseResearch can equally improve the career trajectory of individuals and the academic standing of institutions. Their colleagues respect high academic performers, get promoted, and be recruited to more prestigious institutions \u201311. SimiWe aimed to describe the landscape of AACM research in Africa, and we hypothesized that the most significant contributions to African A.C.C.M. were from South Africa and Western countries.http://www.proz.com, ProZ, Syracuse, New York, U.S.A.). After the database search, Google Scholar, ResearchGate, and ORCiD were searched. This hand search was informed using forward and backward citation analyses, i.e., the articles cited by the studies found during the database search and the articles that cited the studies found during the database search.A protocol was developed and can be accessed online (10.13140/RG.2.2.28999.32167). PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 4, 2020, using a systematic Boolean search strategy . First, duplicates were excluded, then each article was (title and abstract) screened by at least two reviewers . Next, conflicts were resolved by the authors concerned, and if the two authors could not agree, a third author (U.S.K.) was sought for arbitration.The citations were exported then uploaded on the free online review platform - Rayyan then imported into SPSS v26 . The publication trends, author contributions, and hierarchy of evidence frequencies were calculated and visualized using Tableau Public .The absolute number of published articles is a good measure of academic proficiency and research aptitude; however, it does not factor individual contributions at the level of a nation. Countries with more physician anesthesia providers (P.A.P.s) are expected to have higher research outputs. To account for this, the authors chose to calculate the number of articles per African P.A.P.s. This metric was calculated by dividing the number of first author articles by the number of P.A.P.s from each African country. A major barrier to A.C.C.M. research is the lack of protected research time . The P.AP-value <\u20090.05.The data on the P.A.P.s was obtained from a 2015/2016 survey of the World Federation of Societies Anaesthesiologists . Also, cThe search strategy returned 4690 articles: 4688 from databases and 22 from the supplementary hand search. We excluded 705 duplicates and reviewed 3985 non-duplicate articles. After the title and abstract screening, we excluded 2922 more articles because they were irrelevant. Most irrelevant articles returned articles from Papua New Guinea and animal research on guinea pigs in non-African countries Fig.\u00a0.Fig. 1FP\u2009=\u20090.48) , 1993 (14 articles), and 2018 (71 articles) , Anesthesia and Analgesia 51, 5.8%), and Anaesthesia were the top contributors. The top 50 journals are displayed in Table\u00a0, 5.8%, aMost 291, 32.8%) studies had a cross-sectional design. The next most common study designs were cohort studies and randomized controlled trials . There were a few animal studies and published guidelines countries were African, and the median number of first author articles by Africans was 8.5 (IQR\u2009=\u200916.25). The most productive first authors were affiliated with institutions from Nigeria , South Africa , U.S.A. , UK , and Ethiopia but not with the African P.A.P. density .The median number of articles per African P.A.P.s was 0.13 (IQR\u2009=\u20090.38), while the median number of articles per African P.A.P. density was 30.65 IQR\u2009=\u200988.29) articles. Malawi had the highest number of articles per African P.A.P.s (1.67), followed by Togo (1.06), and Sierra Leone (1.00). When taking into account the P.A.P. density, Ethiopia (580.00), Nigeria (336.21), and Malawi (333.33) were the most significant contributors (Table\u00a09 articleThere were 245 (27.5%) single-author articles. Similarly to the first authorship, Nigeria was a major contributor among second authors . South Africa and the U.S.A. were the second and third major contributors to second author positions.While Nigeria remained the major contributor among first authors , South Africa dropped to the third place 47, 5.3%) behind the U.S.A. 74 (8.4%) of African countries did not have first-author publications. This finding is not surprising because African researchers face numerous barriers to publication.Barriers faced by African A.C.C.M. researchers include lack of funding, institutional support, inexperience, and lack of mentorship . ResearcAfrican countries, without first author publications, should collaborate with higher-performing countries. The more experienced African researchers can mentor and build capacity among less experienced researchers in neighboring countries. The African Perioperative Research Collaborative is an excellent example of the potential of inter-African A.C.C.M. research collaboratives. The African Perioperative Research Collaborative is a group led by members of the South African Perioperative Research Collaborative that has facilitated A.C.C.M. clinical research among African researchers via technical support, mentorship, and capacity building , 17.A sizable proportion of the first authors were affiliated to non-African institutions, most of them from high-income countries. This might explain why some countries did not have first-author publications. African researchers often assume the role of middle authors when they collaborate with researchers from high-income countries . The lacThe most substantial increase in publications occurred during the early 2000s, and they can be explained by increased interest in Global Anesthesia. Global Anesthesia is a field at the crossroads between anesthesia and public health that focuses on access to safe, timely, and affordable anesthesia care in the world. The World Federation of Societies of Anesthesiologists (W.F.S.A.) and prominent specialty journals supported research on access to and safety in anesthesia care. For example, the W.F.S.A. was a founding member and a sponsor of LifeBox and the World Health Organization Safe Surgery checklist, respectively , 5, 7. MThere were few systematic reviews and guidelines among the African A.C.C.M. articles. These two forms of information synthesis are among the highest forms of scientific evidence and should inform practice . The intAlso, there were few animal studies among the African A.C.C.M. publications. Although animal studies generate lower-grade scientific evidence, they are essential to the development of A.C.C.M.. For example, animal research played an essential role in developing the Guedel cannula, curarisation, and motor blocks . Africa\u2019A significant proportion of the top 50 journals were specialty journals, and only one of the specialty journals was African. Unsustainable financial models can explain the dearth of African specialty journals, lack of editorial expertise, and low submissions quality . All theThe African Journal Partnership Program model should be supplemented by inter-African partnerships between more and less experienced journals. The top contributing journal was South African, and the only African specialty journal was equally South African and emphasized the critical role of South African journals in A.C.C.M. research. The prominence of South African journals is an opportunity for other journals to learn from a successful African editorial staff.A considerable number of articles were published in non-local high impact factor specialty journals. Similar trends have been observed in Europe and South Asia , 39. PubGoing forward, African A.C.C.M. research must adopt a \u201cno woman/man left behind\u201d approach. Continental-level professional groups like the Africa Regional Section of the World Federation of Societies of Anesthesiologists should oversee a continental research agenda focused on capacity-building, especially in countries without first author publications. The capacity-building could be organized online and in-person . These training sessions should be opened not only to specialist physicians but equally to nurse anesthetists, residents, and medical students. Nurse anesthetists, residents, and medical students can help decrease the research workload by contributing to data curation, project administration, and writing of original manuscript drafts. In the absence of protected research time, this strategy can \u201cbuy\u201d some time for specialist physicians and build capacity among non-physicians.We acknowledge the following limitations in our study: our definition of African research excluded Africans\u2019 research about A.C.C.M. in other continents. Next, we considered studies to be equal irrespective of their citation metrics or study design. Therefore, we did not factor the impact of the studies into the contributions. Hence, a letter to the editor with lower citation metrics was considered equal to a systematic review with higher citation metrics. Finally, we limited our analysis to prominent author positions. As such, we failed to capture a detailed picture of the contributors to African A.C.C.M. research. In addition, our search strategy could have been more explicit. We initially opted for a more comprehensive search strategy, but the results returned many irrelevant results. Given our limited resources, we opted for a less broad search. Despite these limitations, we believe our study adds value to existing research.This study analyzed the publication trends, study designs, target journals, and contributions to A.C.C.M. research in Africa. There has been an increase in article publication over the past two decades, and the greatest contributors are Nigeria and Malawi. This analysis helped to identify less productive countries, subspecialties, and study designs. As such, our findings can be used to set the A.C.C.M. research agenda in Africa.Additional file 1. Search Strategy.Additional file 2. African anesthesia and critical care medicine research output by study design."} +{"text": "A), the effectivenumber of alleles (NE ) based on the locus, the rarified allelic richness (AR), the observed (HO ) and expected (HE )heterozygosity,and the fixation index (FIS) were calculated. The degree of genetic differentiation of the breeds wasassessed based on the pairwise values of FST and D. The analysis of the allelic and genetic diversity parameters ofthe local breeds showed that the maximum and minimum levels of polymorphism were observed in pigs of theUkrainian White Steppe breed and in pigs of the Duroc breed , respectively. The highest level of genetic diversity was found in the Large White breedof the Republic of Belarus (HO = 0.707 and NE = 0.702). The minimum level of genetic diversity was found in pigs ofthe imported breeds \u2013 the Landrace and the Duroc \u2013 indicating ahigh selection pressure in these breeds. Based on the results of phylogenetic analysis, the genetic origin of LargeWhite pigs, the breeds, from which the Berkshire pigs originated, and the genetic detachment of the Landrace fromthe Mangalitsa breeds were revealed. The cluster analysis showed a genetic consolidation of the Black-and-White,the Berkshire, and the Mangalitsa pigs. Additionally, the imported breeds with clustering depending on the originwere characterised by a genetic structure different from that of the other breeds. The information obtained fromthese studies can serve as a guide for the management and breeding strategies of the pig breeds studied, to allowtheir better use and conservation.One of the main tasks of genetics and animal breeding is the assessment of genetic diversity and thestudy of genetic relationships between different breeds and populations using molecular genetic analysis methods.We analysed the polymorphism of microsatellites and the information on the state of genetic diversity andthe population structure of local breeds in Russia: the Kemerovo, the Berkshire, the Liven, the Mangalitsa, and theCivilian; in the Republic of Belarus: the Large White and the Black-and-White; and in Ukraine: the White Steppe, aswell as commercial breeds of imported origin of domestic reproduction: the Large White, the Landrace, and theDuroc. The materials used for this study were the tissue and DNA samples extracted from 1,194 pigs and DNA ofthe UNU \u201cGenetic material bank of domestic and wild animal species and birds\u201d of the L.K. Ernst Federal ResearchCenter for Animal Husbandry. Polymorphisms of 10 microsatellites were determined according to the previously developed technique using DNAanalyser ABI3130xl. To estimate the allele pool of each population, the average number of alleles (N Currently, the industrial production of pork is based on theuse of a limited number of commercial breeds of importedpigs. These breeds are well adapted for use in intensive productionsystems, aimed at maximising the genetic potentialof productivity . Along with breeds ofimported origin, there are local breeds that are carriers ofunique forms of variability and constitute the national geneticresources of agricultural animal species. Despite their smallsize, local breeds have not lost their importance in the modernconditions of the development of animal husbandry. Havinga lower productivity compared to commercial ones, suchbreeds are characterised by a greater individual variability,constitutional strength, stress resistance and good adaptationto local climatic conditions .Nowadays, local breeds are considered irreplaceable geneticresources for the creation of geographically oriented systemsfor organic production of livestock products. Accordingto Stolpovsky (2013), due to the inclusion of transnationallivestock industries in the agriculture world, there is a dangerof a reduction of the national genetic resources, dependenceon food imports, and breeding achievements, and there is athreat of globalisation of the spread of infections and hiddengenetic defects. This implies an increasing importance notonly to study the gene pool of species of foreign origin of theanimals but also the conservation of genetic resources of thelocal breeds.According to the guidelines for the development of nationalplans for the management of farm animal genetic resources, FAO proposes an integrated global managementof farm animal genetic resources using microsatellite referencemarkers . Todate, there are many publications that show the applied importanceof STR for characterising the genetic diversity andstructure of pig breeds for commercial and local breeding. However, comparative studies of the entire variety of local and commercialbreeds of pigs bred in Russia have not yet been carried out.The aim of this study was to characterise the genetic diversityand population structure of eight local and three commercialpig breeds based on the analysis of microsatellites.The object of research was biological material obtained from1,194 pigs, which was stored in the UNU \u201cGenetic materialbank of domestic and wild animal species and birds\u201d of theL.K. Ernst Federal Research Centre for Animal Husbandry.Tissue samples (ear pinch) were used as biological material.The presented sample included eight local breeds bred inRussia: the Kemerovo , theBerkshire , the Liven , the Mangalitsa , the Civilian ;The Republic of Belarus: the Large White andthe Black-and-White ; and Ukraine: the WhiteSteppe , as well as three commercial breeds ofimported origin of domestic reproduction, bred in the breedingand genetic centres of Oryol, Voronezh, and Lipetsk regions:the Large White , the Landrace ,and the Duroc .DNA isolation was performed using DNA-Extraction kitsfor genomic DNA isolation , in accordancewith the manufacturer\u2019s protocol. Analysis of polymorphismsof ten microsatellites wascarried out according to the previously described method. The results of the amplified fragmentswere visualised using fragment analysis by using GeneMapper v. 4 software .ST and D and the construction of phylogenetic trees using theNeighbor-Net algorithm were performed in GenAlEx 6.503 , SplitsTree 4.14.5 software and R package \u02bbdiveRsity\u02bc, with subsequentvisualisation using the package \u2018pophelper\u2019 .Analysis of population genetic parameters, the degree ofgenetic differentiation based on matrices of pairwise values ofFThe genetic structure of the studied pig breeds was assessedusing principal component analysis (PCA) in R package\u2018\u0430degenet\u2019 and was visualised using R package\u2018ggplot2\u2019 and through clustering usingSTRUCTURE 2.3.4 software , usinga mixed model . For each value of K,10 iterations were performed. Structure Harvester was used to determine the optimal number ofclusters (\u0394K), according to the method proposed by Evannoet al. (2005). Source files were generated in Microsoft Excelformat and R 3.5.0 software environment (R Core Team).O) and expected (HE) heterozygosity were noted at the SW951 locus: 0.437 \u00b1 0.067 and 0.482 \u00b1 0.071, respectively.Locus SW857 had the maximum values of indicators:HO = 0.868 \u00b1 0.018 and HE = 0.783 \u00b1 0.018.In the analysis of genotypes of ten microsatellites for the entiresample, 69 alleles were detected, which exceeded the numberof alleles detected in the molecular genetic analysisof the Chinese pig breed with a similar number of markers. Locus SW951 had the lowest number ofalleles . A similar trend for this locus was revealedin studies of pigs bred in Ukraine and Thailand .The greatest number of alleles (22) was found at the SO005 locus,which was consistent with the results of the studies byGuastella et al. (2010) and \u0160alamon et al. (2019), in whichthis locus exceeded the others in the number of alleles: 19 and17 alleles, respectively. The minimum mean values of bothobserved showed significant deviations from the state of geneticequilibrium at individual loci in all the breeds studied. InLandrace pigs, deviations from the genetic equilibrium werefound at all loci, in Duroc and Large White pigs, at nine andeight loci, respectively. It should be noted that local breedsof pigs were inferior to commercial breeds in terms of thenumber of loci with significant deviations from the state ofgenetic equilibrium. The number of such loci varied from threein the Liven breed to seven in the Ukrainian White Steppebreed. These findings can indicate greater selection pressuresin commercial pig breeds, compared to local breeds. Of theten studied loci, highly significant deviations from the geneticequilibrium were established for the SO005 locus, accordingto Hardy\u2013Weinberg ( p < 0.001).An interesting research result published by Kramarenko etal. (2018) showed that in pigs of the Duroc breed bred in theregions of Ukraine, eight out of twelve loci had insignificantdeviations from the state of genetic equilibrium.A = 4.875) were observed inthree breeds: CVL, MNG, and DUR, and the maximum values(more than 6.000) were observed in Landrace pigs and in the Large White breed bred in the territoriesof our country and in Ukraine . The values of the number of effective allelesper locus (NE) ranged from 2.119 (DUR) to 3.709 (LWUK).To assess the degree of genetic diversity of populationsand breeds, two main indicators are most often used \u2013 thelevel of polymorphism and the degree of homozygosity(heterozygosity) , whose results arepresented in Table 2. The minimum values of the averagenumber of alleles per locus (NR), which is considered as a strongindicator of the evolutionary potential of a population , and it hasbeen suggested that this indicator is of key importance for theconservation and management of the population . The minimum values of this indicator, whichwere corrected using the rarefaction method, were detected forDUR \u2013 AR = 3.821, and were maximal in LWUK \u2013 AR = 6.020.According to Greenbaum et al. (2014), a decrease in allelicdiversity may lead to a decrease in the population\u2019s ability toadapt to future environmental changes. Moreover, accordingto Wagner (2008), there is evidence that a high allelic diversity,even of simple neutral alleles, increases the evolutionarypotential by making less genotypic space available formutational events.Another measure that characterises the level of polymorphismis allelic diversity (AO) and expected (HE ) heterozygosity. The HO in the studied breeds ofpigs ranged from 0.459 \u00b1 0.095 for LDR to 0.707 \u00b1 0.052 forBLW. According to some authors, a decrease in HO can leadto a decrease in the average fitness of individuals, and, therefore,this indicator has clear ecological consequences . Moderate levels of HE(above 0.5) were observed in nine pig breeds, ranging from0.545 \u00b1 0.095 for MNG, to 0.709 \u00b1 0.028 for LWUK. Pigsof the Duroc and the Lansrace breeds were an exception, inwhich this indicator had minimum values: 0.469 \u00b1 0.070 and0.490 \u00b1 0.073, respectively.To date, the most commonly used indicators of the geneticcharacteristics of populations presented in most studiesare the observed with a variation ofpositive values of the indicator from 0.036 for LW, to 0.139for KEM. However, for these breeds, with the exception ofKEM and LWUK, the 95 % confidence interval (CI) of thefixation index included the zero value, which indicates nonsignificantdeviations in the number of heterozygotes fromthe theoretically expected, in these breeds. A slight shift inthe genetic balance towards an excess of heterozygotes wasnoted in four breeds: LIV, BLW, BBP, and DUR, in which thefixation index had negative values, which amounted to 0.060,0.002, 0.008 and 0.014, respectively.A = 6.500, NE = 3.709,AR = 6.020), and the maximum level of genetic diversity wasfound in BLW . At the same time, pigs of the Mangalitsa breed had minimum values for all theanalysed parameters: NA = 4.875, NE = 2.723, AR = 0.659,HO = 0.524, and HE = 0.545. However, in an study by Drumlet al. (2012), the values of genetic parameters characterisingthe level of genetic diversity of pigs of the Mangalitsa breed ofAustria and the National Reserve of Serbia were even lower:NA = 3.8, HO = 0.49, and HE = 0.54 and NA = 3.94, HO = 0.58,and HE = 0.54, respectively. When comparing the animals ofimported origin of domestic reproduction, the group of largewhite pigs exceeded the other two in all aspects: NA = 6.250,NE = 3.349, AR = 5.126, HO = 0.651, and HE = 0.672. Of all thestudied pig breeds, the minimum level of polymorphism andgenetic diversity was found in the Duroc breed: NA = 4.875,NE = 2.119, AR = 3.821, HO = 0.480, and HE = 0.469. A similartrend towards a relatively low level of genetic diversityof this breed was noted in the works of other authors. In acomparative analysis of local breeds of Brazil with pigs ofspecialised breeds , theminimum values of both the average number of alleles perlocus and the effective number of alleles were identified in theDuroc breed, which amounted to NA = 3.65 and NE = 3.01 . In his work, Szmato\u0142a et al. (2016), whilestudying the genetic diversity of four commercial breeds andone local breed of pigs in Poland using five microsatellites,he revealed the lowest values of the average number of allelesper locus (NA = 4.6), the number of effective alleles per locus(NE = 2.78) and allelic diversity (AR = 4.6). However, thestudies by Kim et al. (2005), which focused on the descriptionof the genetic diversity and population structure of fourEuropean, two Korean and three Chinese pig breeds, showedthat Duroc pigs outnumbered others in these parameters. Atthe same time, local Korean pigs showed consistently lowlevels of allelic diversity and heterozygosity, while Chinesepig breeds, except for the Wuzhishan breed, had a relativelyhigh degree of genetic diversity compared to commercialand local Korean pig breeds. The lower values of populationgenetic parameters detected in our work, both in pigs of theMangalitsa and the Duroc breeds, possibly indicates a highselection pressure and a minimal or no migration of newgenes in the breeds.Among the local breeds, the maximum level of polymorphismwas observed in LWUK , as well as coordination analysis, using PCA .Despite the fact that the algorithm based on the values of \u0394K revealed that the optimal number of clustersfor this sample is equal to 9, K = 9 (\u0394K = 136.79), the resultsat K = 11 were also presented.The breeds LIV, BLW, and LW are characterised by amixed genetic origin. In addition, a similar genetic patternwas observed in the CVL and LWUK breeds. A clear genetic structure has been identified in black-and-white, Berkshire,and Mangalitsa pigs. The formation of several clusters ofbreeds of imported origin is explained by both different originsand different strategies of selection and the breeding workused in the enterprises.Principal component analysis, the key feature that enablesthe projection of samples onto orthogonal coordination axes,each of which consisting of a linear combination of allelicor genotypic values , revealed a genetic mixing and enabled the visualisationof a slight differentiation for most of the studied breeds.Independent cluster formed by representatives of commercialbreeds ; at the same time,local breeds formed overlapping arrays. According to Jolliffeand Cadima (2016), the lack of clear clustering does not meanthe absence of differences but may indicate the similarity ofthe largest source of variability. In addition, this analysis madeit possible to characterise the range of variability in threecomponents. The first component was responsible for mostof the genetic variability of the entire data set (4.3 %), whilethe second and third components reflected 3.7 and 2.8 % ofgenetic variability, respectively.ST andNei\u2019s GST, and indicators of allelic differentiation, such asJost\u2019s D and differential entropy . One of themost commonly used indicators in population genetic studiesis the standard method for estimating the FST fixation index,described by Weir and Cockerham (1984). However, whencalculating the genetic distances based on the variability ofhighly polymorphic markers, the values of the indicator maybe shifted .Therefore, we additionally performed calculations of theD index proposed by Jost (2008) that takes into account theproportion of allelic variations in populations (Table 3).To assess the degree of differentiation of populations, twomain classes of indicators that determine the quantitativestructure of populations are used: fixation indices FST = 0.037, D = 0.064. However,regarding the maximum values of the indices, differenceswere detected: the greatest genetic distance, according to theFST fixation index, is characteristic of the LDR/CVL = 0.244group, and the LW/DUR = 0.291 group, according to theD index.The greatest genetic affinity for both indicators was foundfor pigs of the Russian and Belarusian populations of the LargeWhite breed: LW/BLW FST and D, were visualised using the Neighbor-Netalgorithm and are presented in Figure 3. A separate massif wasformed by groups of root pigs of a large white breed and adjacent branches of the Kemerovoand Liven breeds. A separate branch is a cluster of breedsin the creation of which pigs with the blood of the Berkshirebreed took part: BBP, BERK, and DUR. The Landrace andthe Mangalitsa animals are presented in a separate cluster.To visualise the genetic degree of closeness of the studiedpig breeds, the numerical matrices of the pairwise geneticdistances, FOur studies were aimed at analysing the genetic diversity andstudying the relationship between eight local pig breeds andthree pig breeds of imported origin of domestic reproduction.In general, the studied local breeds exceeded the groups ofimported pigs in both allelic and genetic diversity, whichis probably explained by the lack of a practical program ofcontinuous improvement of specific characteristics, to whichcommercial breeds are subject. On the contrary, the maximumpositive values of the fixation index were detected in localbreeds (Kemerovo and Ukrainian White Steppe), which canlead to a shift in the genetic equilibrium towards a lack ofheterozygotes. The analysis of the main components, carriedout on the basis of the allele frequencies of the studiedbreeds of pigs, made it possible to characterise the range ofvariability and trace the main patterns of population geneticdifferentiation of individuals of the studied breeds of pigs. The information obtained from these studies can guide themanagement and breeding strategies of the studied breeds inorder to better use and conserve them. At the same time, furtherstudies of pigs, both local and specialised breeds, with manymicrosatellites, using mitochondrial DNA and single nucleotidepolymorphism analysis, seem necessary. Future geneticprogress will mainly depend on the availability of sufficientgenetic variation, and a more holistic understanding of thestate of genetic diversity and the structure of pig breeds willbring tremendous benefits for the entire pig industry.The authors declare no conflict of interest.Allendorf F.W. 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Selskokhozyaystvennaya Biologiya = Agricultural Biology.2012;6:35-42. (in Russian)"} +{"text": "Petrocosmeananchuanensis Z.Y. Liu, Z.Y. Li & Z.J. Qiu from Mt. Jinfo at Banhe valley of Nanchuan District in Chongqing Municipality (China) is described and illustrated for the first time. Even though this new species is similar to Petrocosmeabarbata, it has several significant morphological differences, which includes smaller leaves, repand leaf margin, densely appressed longer pubescences on both surfaces of leaves, larger flower with length of its lower lips about three times longer than that of the upper lips, oblong lower lip lobes, shorter pistil, ovate anthers and styles that are shortly pubescent or approximately glabrous above the middle. The distinct features of P.nanchuanensis and four relative species namely, P.barbata, P.longipedicellata, P.cavaleriei and P.xanthomaculata were also represented in depth. However, P.nanchuanensis is most closely related to P.barbata, based on molecular studies.A new species, Petrocosmea Oliver, (1887) was established in 1887. At present, Petrocosmea genus consists of 50 species classified into five sections: sect. Petrocosmea Oliv., (1919), sect. Anisochilus Hemsl., (1899), sect. Minor Zhi J. Qiu, (2015), sect. Barbata Zhi J. Qiu, (2015) and sect. Deinanthera W.T. Wang, (1985) , 2015. HMeasurements and observations of morphological characters of the new species, based on living individuals and specimens, were carried out in the field or greenhouse and at the herbarium. Hairs and glandular hairs and other tiny morphological characters were observed and measured by using a stereomicroscope (Nikon SMZ18). Morphological comparisons with related species were measured, based on living individuals in the greenhouse and specimens from PE, SZBG and KUN herbaria.Taxon classificationPlantaeLamialesGesneriaceaeZ.Y. Liu, Z.Y. Li & Z.J. Qiusp. nov.8F24267E-FA0C-56A1-B357-61F8AFBDE16Curn:lsid:ipni.org:names:77211190-1Petrocosmeananchuanensis is morphologically similar to P.barbata Craib, but is distinguished from the latter by smaller leaves, a repand leaf margin, densely appressed longer pubescences on both surfaces of its leaves, larger flower with the length of its lower lips three times longer than that of the upper lips, oblong lower lip lobes, shorter pistil, ovate anthers and styles that are shortly pubescent or approximately glabrous above the middle.Z. Y. Li 2002016 .China. Chongqing Municipality: Nanchuan, Banhegou, Mt. Jinfo, 20 Sep 2002. Perennial herb, rosette-forming, with a short rhizome and crowded fibrous roots. Leaves 8 to 30, all basal, crowded, the inner leaves with short or absent petioles, the outer leaves with longer petioles; leaves orbicular-ovate, broad-ovate, cordate or almost circular, 0.5\u20132 \u00d7 0.7\u20132 cm, herbaceous, apex round, base cordate, margin undulate teeth, both surfaces with densely villous, lateral veins 3 on each side, not distinct; petioles 0.5\u20136 cm, densely pilose. Cymes 5 to 15, 1\u20133 flowers per cyme; peduncle 3\u201310 cm, densely pilose; bracts 2 at upper- or middle-peduncle, lanceolate, 0.5\u20131.2 cm, pubescent, pedicel 1\u20135 cm, densely hairy; sepals 5-divided to the base, narrow-lanceolate, ca. 4\u20135 mm, pubescent externally. Corolla light purple or white, outside and inside abaxial lip puberulent, inside adaxial lip and tube near mouth densely pubescent, 2 yellow spots inside abaxial lip base; tube ca. 3 mm, adaxial lip ca. 3\u20133.5 mm, bi-lobed near to base, lobes ovate, abaxial lip ca. 8\u20139 mm, deeply tri-lobed, lobes oblong; stamens 2, ca. 2.2 mm; filaments adnate to ca. 1 mm above the base of corolla tube, ca. 1.2 mm long, glabrous; anthers ovate, ca. 1 mm long, glabrous; staminodes 3, adnate to ca. 0.2\u20130.4 mm above the base of the corolla tube, ca. 0.3\u20130.8 mm long, glabrous; pistil ca. 4.5 mm; ovary densely villous, ovoid, oblique abaxially, ca. 1.5 mm long; style unfolded pilose and glandular hairs under the middle, shortly pubescent or approximately glabrous above the middle, ca. 3 mm long.Petrocosmeananchuanensis grows on moist shady limestone cliffs or along forest edges at an altitude of 600\u2013650 m on the Mt. Jinfo, Banhe valley, Nanchuan District, Chongqing Municipality, which is adjacent to Guizhou Province in south-western China.2 and 550 individuals were found at the other location with ca. 8 \u00d7 3 m2. Petrocosmeananchuanensis is only known from the type locality, i.e. Nanchuan District and their habitat has been threatened and damaged by deforestation and over-exploitation due to native tourism despite its protection in the Mt. Jinfo National Nature Reserve.The new species is determined to be Critically Endangered (CR A2c) according to the IUCN Red List of Threatened Species Categories and Criteria . About 8The new species was collected with flowers during September\u2013November; fruits were not seen.R. H. Liang 2007010 (PE), Z. J. Qiu 2011020, QZJ-20131082 (SZG), S.Z. Zhang 20121077 (SZG), Z. Y. Liu 500119-1582ly, 500119-1595ly (IMC).China. Chongqing: Mt. Jinfo, Nanchuan, 3 Sep 2007, Petrocosmea genus which includes P.nanchuanensis has been studied using six chloroplast DNA regions and two nuclear DNA regions (ITS and PeCYC1D) , P.longipedicellata W.T. Wang, (1985) and P.cavaleriei Levl., (1911), as shown in Fig. P.nanchuanensis, P.barbata, P.longipedicellata and P.cavaleriei, has some morphological synapomorphies, such as two yellow spots at the base of the lower lip lobes, densely villous on the ovary, villous inside corolla tube and glabrous filaments. The phylogenetic tree revealed that P.nanchuanensis is most closely related to P.barbata that also belongs to sect. Barbata.In our previous study, molecular phylogenetic analysis of PeCYC1D) . The molP.nanchuanensis and its related species namely, P.barbata, P.longipedicellata, P.cavaleriei and P.xanthomaculata G.Q. Gou & X.Y. Wang (2010). Herein, both morphological and our previous molecular studies support P.nanchuanensis as a new species and being most similar to P.barbata. The foremost morphological differences between P.nanchuanensis and P.barbata include that P.nanchuanensis has smaller leaves than P.barbata and P.nanchuanensis leaves have an undulate-toothed margin, whereas, P.barbata has a crenate margin. Moreover, P.nanchuanensis shows a densely appressed villous on both surfaces of leaves instead of the adaxially puberulent and abaxial slightly and densely puberulent pattern of P.barbata.Table P.nanchuanensis has larger flowers than P.barbata, in which P.nanchuanensis has flowers about three times longer in lower than in upper lips instead of about two times longer in lower than in upper lips in P.barbata. Additionally, lower lip lobes are oblong in P.nanchuanensis instead of broadly ovate in P.barbata, while P.nanchuanensis has a shorter pistil than P.barbata. Besides, P.nanchuanensis has styles that are shortly pubescent or approximately glabrous above the middle instead of styles with unfolded villous and short glandular hairs under the top and short glandular hairs on the top in P.barbata. The P.nanchuanensis has ovate instead of round-ovate anthers in P.barbata.Likewise, Petrocosmeananchuanensis belongs to sect. Barbata due to its floral structure, particularly anthers that are not constricted near the apex, the length of its abaxial corolla lip being twice as long as the adaxial and two yellow spots at the base of the lower lips lobes. Even though, this new species is similar to P.barbata and mostly varies through smaller leaves, a repand leaf margin, densely appressed longer pubescences on both surfaces of its leaves, larger flowers with their lower lips about three times longer than the upper lips, oblong lower lip lobes, shorter pistil, ovate anthers and shortly pubescent styles or approximately glabrous above the middle.We conclude that P.nanchuanensis and P.barbata has been supported by our previous molecular phylogenetic data (P.nanchuanensis is most closely related to P.barbata (Figure Morphological similarity between tic data . A phyloa Figure , which i"} +{"text": "Gnetumchinensesp. nov., a new lianoid species of Gnetaceae, is described from southwestern China. The new species is morphologically similar to G.montanum Markgr. in its oblong elliptic leaves and the ovoid to ellipsoid chlamydosperm, but differs from the latter by its shorter male spikes having fewer involucral collars (7\u201310 vs. 13\u201318 in G.montanum). We also did a new molecular analysis using one nuclear marker (i.e. nrITS) and four chloroplast markers . The result suggests that this specific clade is sister to a large clade consisting of all other known Chinese lianoid species of Gnetum except G.parvifolium (Warb.) W.C. Cheng. Gnetum L., belongs to the monotypic family Gnetaceae of gymnosperms, and contains ca. 40 extant species that are widely distributed in tropical and subtropical forests in Asia, Africa and South America fruiting material is poorly represented in herbaria, and ii) it is difficult to match male and female specimens to a certain species when studying a dioecious taxon like Gnetum.rn China . Cheng W.C. Cheng, and G.pendulum C.Y. Cheng.Molecular phylogeny was successfully applied to the delimitation of species of aracters . Kim andGnetum species was identified when we worked on a Gnetum genome project a few years ago. Further morphological and molecular studies on newly collected materials during field investigations in southern China allowed us to describe this species here as new to science.A new PE), State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences were targeted. Gnetum sequences generated in Total genomic DNA was extracted from the dried leaf materials using the CTAB method and purif Gnetum . We follG.africanum Welw. as the outgroup. Maximum likelihood (ML) analyses were conducted using the RAxM L-HPC2 on XSEDE (8.0.0) executed in the CIPRES portal for each node were summarized after 1,000 replicates of bootstrapping iterations. The obtained trees were viewed and edited using FigTree ver. 1.4.0 (http://tree.bio.ed.ac.uk/software/figtree/). Bayesian inference (BI) analyses were performed using MrBayes 3.2.6 (MCMC) algorithm was run for 3,000,000 generations with the sampling frequency 1,000. Bayesian posterior probabilities (PP) were calculated for the majority consensus tree of all sampled trees after discarding trees sampled within the burn-in (25%) phase in MrBayes v.3.2.1.Previous studies suggested that the African species are sister to all Asian species , as a rees 3.2.6 on XSEDEhttp://www.esri.com). The photos were taken using digital cameras (Nikon D700 and Olympus TG-3), manually edited and created using Adobe Photoshop CS2 ver. 9.0. Phylogenetic trees were viewed and adjusted using FigTree ver. 1.4.0 (http://tree.bio.ed.ac.uk/software/figtree/).The distribution map was generated using ArcGIS 9.3 . Ten samples of G.parvifolium constituted a sister group to a clade consisting of the rest of the lianoid congeners from China included in this study. The analyses revealed the 11 newly collected specimens as a monophyletic group sister to a clade composed of G.formosum, G.catasphaericum, G.luofuense, G.montanum and G.pendulum. Delimitations between G.montanum and G.pendulum were not resolved. The two samples of G.formosum formed a weakly supported group , which was followed by a split between the strongly supported G.catasphaericum and a large clade containing a subclade of Gnetummontanum, G.pendulum, G.giganteum H. Shao, and G.gracilipes , and another one of G.hainanense C.Y. Cheng ex L.K. Fu et al. and G.luofuense . Delimitations between the two species were not resolved.The ree Fig. , in generee Fig. . All ChiTaxon classificationPlantaeGnetalesGnetaceaeY. Yang, Bing Liu & S.Z. Zhangsp. nov.77DD1B45-1A13-5730-AD08-D0752659A11Furn:lsid:ipni.org:names:77209708-1st, 2015, B. Liu, Y. Yang & T.W. Xiao 2627 .China. Yunnan: Cang-yuan County, on the way from Ban-hong to Ban-lao Prefecture, forest margin, male cones, March 31G.montanum in its oblong elliptic leaves and subsessile chlamydosperm, but differs from the latter by its shorter male cones (1\u20131.5 cm long in the new species vs. 2\u20133 cm in G.montanum) having fewer involucral collars (7\u201310 in the new species vs. 13\u201318 in G.montanum), nearly sessile or extremely shortly stiped chlamydosperms .This species is similar to Lianas; twigs terete, dichasially branched having swollen nodes. Leaves opposite Fig. , oblong In Yunnan and Guizhou provinces of China Fig. .In evergreen tropical and subtropical forests.chinense\u2019 is derived from China.The specific epithet \u2018Blooming male cones and mature chlamydosperms were found in late May and early November, respectively.Gnetumchinense is common in evergreen forests in Yunnan and Guizhou. We consider this species to be of Least Concern (LC) under the IUCN Red List Categories and Criteria ver. 3.1 second edition ; Jiang-cheng County, Qu-shui Prefecture, Apr. 18, 2015, B. Liu 3045 (PE); Ma-li-po County, March 15\u201317, 2015, T. Wan MLP001, MLP002, MLP003, MLP 005 (PE); Ma-li-po County, Xia-jin-chang Prefecture, Li-jia-wan, May 27, 2011, B. Liu 1360 (PE); Ma-li-po County, Xia-jin-chang Prefecture, Li-jia-wan, Sept. 24, 2011, B. Liu 1441 (PE); Ma-li-po County, Xia-jin-chang Prefecture, Li-jia-wan, Nov. 2, 2012, B. Liu 1725 (PE). Guizhou: unknown collection date, C.Y. Deng CYD12466 (PE).Gnetum, including a South American clade, an African clade, and several Asian clades .Phylogenetic methods were successfully applied to discover and delimit species of Asian Gnetum . Our phyG.montanum in the shape of leaves and chlamydosperms, and to G.parvifolium in the length of the male spikes and number of involucral collars, but differ from G.montanum by their shorter male cones having fewer involucral whorls, and from G.parvifolium by their larger leaves 11\u201316 cm long and bigger chlamydosperms ca. 2.2 cm long .We did a morphological comparison between our new species and those known lianoid species from China Table , and fouA few morphological details of the new species are taxonomically important but not known to us, e.g. shape and the number of sterile ovules in male spike. As a result, further field investigations are encouraged."} +{"text": "The Editors-in-Chief have retracted this article (Palmblad et al. Dr. Karin Palmblad, Dr. Anna-Carin Horne, Dr. Helena Erlandsson Harris, Dr. Jan-Inge Henter and Dr. Ulf Andersson agree to this retraction. Dr. Hanna Schierbeck and Dr. Erik Sundberg have not responded to any correspondence from the editor/publisher about this retraction."} +{"text": "Tang F, Chen C, Zhu Y, et al. Comparison between flipped classroom and lecture-based classroom in ophthalmology clerkship. Med Educ Online. 2017;22(1):1395679.https://doi.org/10.1080/10872981.2017.1395679When the above article was first published online, the tables were published without footnotes. This has now been corrected in the online version as below."} +{"text": "Thesiumbrevibracteatum P.C.Tam was described, based on the specimen L.C.Chiu 5128 collected from Inner Mongolia, China. The name Thesiumbrevibracteatum Sumnev. is validly published and described for the type (Korotkova E. E. et Titov V. S. 1502) collected from Uzbekistan. T.brevibracteatum P.C.Tam is a later homonym of T.brevibracteatum Sumnev.T.longiperianthium as the replacemen name for T.brevibracteatum P.C. Tam.We propose Thesiumbrevibracteatum P.C.Tam was described, based on the specimen L.C.Chiu 5128 collected from Inner Mongolia, China. It is a sub-fruticose herb up to 30 cm tall and grows on the sunny side of dunes and hills and steppes collected from Uzbekistan . It grows on the northern slopes in the upper parts of mountains on fine-grained slopes in woody and shrubby thickets , the epithet \u201clongiperianthium\u201d has not previously been used for the genus Thesium. Thus, we propose the new name T.longiperianthium for T.brevibracteatum P.C.Tam.During the preparation of the checklist of vascular plants of Central Asia, we realised that the name ountries . In the X.H.Xu & W.Jun Linom. nov.C7836306-6696-4795-8A3B-Eea9609Cd7A9urn:lsid:ipni.org:names:77212687-1\u2261Thesiumbrevibracteatum P.C.Tam in P.C.Tam (1981) New materials on Santalaceae. Bulletin of Botanical Research 1: 73, nom. illeg.Thesiumlongiperianthium X.H.Xu & W.Jun Li, nom. nov.\u2261 Thesiumbrevibracteatum P.C.Tam, 1981., New materials on Santalaceae. Bulletin of Botanical Research 1: 73. nom. illeg.L.C.Chiu 5128 (HolotypeSHM 0009016!).Type:\u2014CHINA. Inner Mongolia: Xilin Gol Meng, Yikenao, 7 Sep 1965,"} +{"text": "Meiogynekwangtungensis is a rare species endemic to Hainan, China, known just from two fruiting collections made in the 1930s. Although it was published under the name Meiogyne in 1976, it was suggested that it might be better placed within Pseuduvaria or Mitrephora. For decades, this species was never collected again, thus its true generic affinity remained unresolved due to the lack of flowers. During a field exploration in Hainan, we re-discovered this species and collected a flowering specimen for the first time. The flower immediately confirmed its affinity with Pseuduvaria. Phylogenetic analyses of five chloroplast regions also unambiguously placed Meiogynekwangtungensis in the Pseuduvaria clade . Morphologically, it is most similar to P.multiovulata which is endemic to Myanmar and Thailand, both with often-paired flowers, long pedicels and short peduncles, and often 1\u20132 monocarps. However, it differs in having smaller flowers with kidney-shaped glands on the inner petals, fewer stamens and carpels, smaller ovoid monocarps with an apicule and fewer seeds. On the basis of the combined molecular phylogenetic and morphological data, we propose a new combination, Pseuduvariakwangtungensis (P.T.Li) Qing L.Wang & B.Xue. A full description including floral characters and a color plate are provided here for this species. A key to species in the genus Pseuduvaria in China is also provided. Meiogyne Miq. is a medium-sized genus in tribe Miliuseae Hook.f. & Thomson of Annonaceae from Hainan, China, in 1935 and 1933 respectively was extracted using a modified CTAB method were newly generated. For detailed information on PCR amplification and primer sequences we refer to Pseuduvaria species from Monocarpiaeuneura Miq. and 14 species in the tribe Miliuseae were selected as outgroups based on the phylogenetic framework reported in previous studies (http://www.ncbi.nlm.nih.gov). The final data matrix comprised a total of 70 species of Annonaceae. The information on sequence alignment can be found in Total DNA of the silica-gel dried material of B method . Five ch studies , 2020a. Detailed information about the samples, localities and GenBank accession numbers are all listed in the Appendix BI) and maximum likelihood (ML) methods. The information on model selection of the sequence matrix constructed could refer to matK and rbcL; and GTR + \u0393 selected for atpB-rbcL, psbA-trnH and trnL-F regions. Detailed methods for tree reconstruction could refer to Phylogenetic analyses were done using Bayesian Inference . The Bayesian analyses and ML resulted in similar topologies. The 50% majority-rule consensus tree resulting from the Bayesian analyses under five-partitioned model is shown as Fig. The concatenated alignment of the 70-taxon dataset consisted of 4,261 aligned positions Heusden, M.pannosa J. Sinclair, and M.virgata (Blume) Miq. form a well-supported clade J. Sinclair J.Sinclair in Thailand, both with 1\u20132 flowers per inflorescence, with long pedicels and short peduncles, and often with 1\u20132 monocarps whereas Pseuduvariamultiovulata has larger flowers Fig. . Morpholonocarps . Howeverals Fig. , wherease square . Meiogynwer Fig. , wherease flower . The monmonocarp .Pseuduvaria species is recorded in Yunnan Province, i.e. Pseuduvariatrimera (Craib) Y.C.F.Su & R.M.K.Saunders Pseuduvar0 m tall , whereasins Fig. , whereasins Fig. . The infers Fig. , whereasers Fig. . Pseuduvals Fig. , whereasals Fig. . Pseuduvrps Fig. , whereasarp Fig. .Meiogynekwangtungensis is different from all species in Pseuduvaria. Both the morphological and molecular phylogenetic data support the transfer of Meiogynekwangtungensis to Pseuduvaria, thus a new nomenclatural combination is proposed here. Additionally, as the name Meiogynekwangtungensis was published based on only two fruiting collections lacking flowers, we provide a detailed description of the flower morphology and an updated description for the fruit morphology. A key to the two Pseuduvaria species in China is also provided.Taxon classificationPlantaeMagnolialesAnnonaceae(P.T.Li) Qing L.Wang & B.Xuecomb. nov.4FA7CCE5-DDFC-58B9-857D-84DFAF7252C1urn:lsid:ipni.org:names:77214765-1hai nan jin gou hua (\u6d77\u5357\u91d1\u94a9\u82b1)Meiogynekwangtungensis P.T.Li, Acta Phytotax. Sin. 14(1): 104. 1976.F. C. How 73305 .China. Hainan: Bao-ting Hisen, Xing-long, 25 Jul. 1935, Shrubs to 3\u20134 m tall, d.b.h. ca. 5 cm. Monoecious. Branches black, densely villous when young, glabrescent .Flowering from March to June; fruiting from June to August.Z. Huang 33693 ; Bao-ting Hisen, Qi-xian Mountain, on mountain slopes under forest, alt. 549 m, 25 Apr. 2020, Q. L. Wang BT20200425001 ; alt. 584 m, 28 May 2020, Q. L. Wang BT20200528001, BT20200528002 .China. Hainan: San-ya, Bai-cha Mountain, 13 Aug. 1933, Pseuduvariakwangtungensis was assessed as CR D by P.kwangtungensis was only represented in herbaria by two collections from Hainan, China, collected in 1933 and 1935 respectively. One of the authors, Dr. Qing-Long Wang, has undertaken extensive field surveys in Hainan, and only found this species again in two localities in Qi-xian Mountain in Bao-ting, with three and four mature individuals respectively. Although it\u2019s possible more individuals may be discovered with more extensive field surveys, we intended to maintain the CR category.CR D . Pseuduv"} +{"text": "Angiopteris (Marattiaceae). Based on the analysis of morphology and DNA sequences of multiple chloroplast regions , we revised Angiopteristonkinensis (Hayata) J.M.Camus and proposed a new combination Angiopteristamdaoensis (Hayata) J.Y.Xiang & T.Wang, comb. nov., which was previously regarded as a synonym of A.tonkinensis. We found support for a monophyletic Angiopteris including Protomarattia. This discovery adds two new distribution sites of A.tonkinensis, one in China and one in Vietnam . We suggest A.tonkinensis should be categorised as Critically Endangered (CR) species according to the criteria of IUCN.The border area between south-eastern Yunnan, China and northern Vietnam is one of the regions with richest biological diversity including that of the fern genus AngiopterisAngiopteris. According to Angiopterisbipinnata (Ching) J.M.Camus (A.dianyuecola Z.R.He & W.M.Chu (A.latipinna (Ching) Z.R.He, W.M.Chu & Christenh. (A.sparsisora Ching (A.subrotundata (Ching) Z.R.He & Christenhusz on 18 May 2018 and Quan Ba (northern Vietnam) on 10 Oct 2019, two small populations of ferns caught our attention Protomarattia and Archangiopteris into Angiopteris and transferred Ar.tonkinensis to Angiopteris under the new combination Angiopteristonkinensis (Hayata) J.M.www.tropicos.org)).Protomarattiatonkinensis and Archangiopteristamdaoensis based on four chloroplast regions , then we revised their taxonomic status.In this study, we aimed to explore the identity of the materials collected from Malipo, Yunnan, China and Quan Ba, Ha Giang, Vietnam by means of morphological and phylogenetic studies. We inferred the phylogeny of SWFU), the herbarium of Institute of Ecology and Biological Resources, Hanoi, Vietnam (HN) and Shanghai Chenshan Botanical Garden Herbarium (CSH). For morphological comparisons, primary literature . Fourteen sequences of seven species were newly generated for this study and their voucher information and GenBank accession numbers are presented in Table We analysed 19 samples of trnL-F gene .Total genomic DNA was extracted from silica-gel dried leaves using the TSINGKE plant DNA extraction kit (generic). The sequences were amplified using the primers designed by previous studies: primers e and f for L-F gene , F1 and bcL gene , rps5\u2019 (bcL gene and trnS (trnS R for rps4 atpB-F1 and atpE atpB-F1 for atpBML) analysis with concatenated DNA datasets. PartitionFinder2 (BIC). The best-fit scheme proposed two subsets: and . The best-fit model for subset1 was GTR+G and for subset2 was GTR+I+G. Maximum Likelihood analyses were performed using IQ-TREE v.1.6.8 resolved eight accessions of Protomarattiatonkinensis in a clade clearly separated from Archangiopteristamdaoensis in Quan Ba. Before our study, the species had not been recorded since its publication about 100 years ago. The assessment result shows that P.tonkinensis should be assessed as Critically Endangered (CR). More fieldwork is needed in similar forest regions in south-western China, Myanmar and Vietnam to confirm its distribution and conservation status.In the field, the populations of Protomarattiatonkinensis since its publication. Some suggested that it should be treated as a synonym of Archangiopteristamdaoensis (P.tonkinensis as a \u201cgood\u201d species and argued that Protomarattia should be treated as a different genus (P.tonkinensis to Angiopteristonkinensis (Hayata) J.M.Camus. Protomarattiatonkinensis, however, is distinguishable from Ar.tamdaoensis, previously subsumed under Angiopteristonkinensis by Angiopteristamdaoensis (Hayata) J.Y.Xiang & T.Wang, comb. nov.There have been a number of controversies surrounding daoensis , while ont genus . Based oTaxon classificationPlantaeMarattialesMarattiaceae(Hayata) J.M.CamusD88F4384-A459-5480-B8FB-29A0480FF917ProtomarattiatonkinensisArchangiopteristonkinensis (Hayata) Ching, Ic. Fil. Sinic. V (1958) t. 209. Basionym Hayata, Bot. Gaz. 67: 88. 1919; s.n. Vietnam. Tonkin, 30 July 1917, Bunzo Hayata BX19001 (SWFU); Vietnam. Ha Giang: Quan Ba, Thai An Commune, Seo Lung, 925 m alt., 10 October 2019, L. Averyanov, Nguyen Sinh Khang, T. Maisak, AT1 .China. Yunnan: Zhuang-miao Autonomous Prefecture of Wenshan, Malipo, Hua mountain, Chouyang river, 850 m alt., 18 May 2018, J. Y. Xiang, T. Wang, M. F. Long, Yunnan, China and Northern Vietnam.Taxon classificationPlantaeMarattialesMarattiaceae(Hayata) J.Y.Xiang & T.Wangcomb. nov.43472D22-6939-5243-BBAB-297CFCB99DDAurn:lsid:ipni.org:names:77211596-1ArchangiopteristamdaoensisProtangiopteristamdaoensis (Hayata) Hayata, Bot. Mag. Tokyo 42(498): 309. 1928. Basionym Hayata, Bot. Gaz. 67: 88. 1919; Vietnam Tonkin, August 1917, Bunzo Hayata, s.n.Hainan, China and Northern Vietnam."} +{"text": "Nature Communications 10.1038/s41467-020-20340-8, published online 4 January 2021.Correction to: 1Department of Mathematics, Science for Life Laboratory, Stockholm University, 106 91 Stockholm, Sweden. 2Oxford Nanopore Technologies Ltd, Oxford, UK. 3Department of Computer Science and Engineering, The Pennsylvania State University, University Park, PA, USA. 4Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA. 5Center for Computational Biology and Bioinformatics, The Pennsylvania State University, University Park, PA, USA\u201d to read \u201c1Department of Mathematics, Science for Life Laboratory, Stockholm University, 106 91 Stockholm, Sweden. 2Department of Computer Science and Engineering, The Pennsylvania State University, University Park, PA, USA. 3Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA. 4Center for Computational Biology and Bioinformatics, The Pennsylvania State University, University Park, PA, USA\u201d. The following was added to the Acknowledgements: \u201cWe want to thank Botond Sipos for several substantially helpful discussions regarding data analysis, and Philip L. James for producing the biological sequencing data\u201d. The original version of the Author contribution statement\u201d, which read: \u201cK.S. and P.M. conceived the project. K.S. designed the algorithm with input from P.M. and B.S. K.S. implemented the algorithm. K.S. and P.M. designed the evaluation and experiments. K.S. implemented the evaluation. K.S. and P.M. analyzed the results with input from B.S. B.S. implemented the preprocessing tool pychopper with input from K.S. P.L.J. performed the wet-lab experiments. K.S. and P.M. drafted the paper with contributions from B.S. All authors critically revised the text\u201d, has been amended to read: \u201cK.S. and P.M. conceived the project, designed the evaluation and experiments, analyzed the results, and wrote the paper. K.S. designed the algorithm with input from P.M. K.S. implemented the algorithm and evaluation. All authors critically revised the text\u201d. The Competing interest statement, which originally read: \u201cData generation was funded by Oxford Nanopore Technologies (ONT). B.S. and P.J. are ONT employees and stock option holders. The remaining authors declare no competing interests\u201d, has been amended to read: \u201cData generation was funded by Oxford Nanopore Technologies (ONT). The remaining authors declare no additional competing interests\u201d.The original version of this Article included second and third authors who wish to be removed from authorship and instead mentioned in the Acknowledgements. Consequently, the author affiliation for these authors has been removed and the equal contributions statement has been removed. The author affiliations have changed from \u201cThis has been corrected in both the PDF and HTML versions of the Article."} +{"text": "Lobelia L. . Lobelia habitats in East Africa have been facing habitat fragmentation and loss, which are recognised as a major threat to biodiversity. However, previous plant conservation studies in East Africa only focused on protected areas and ignored unprotected areas. Future conservation strategies of plants, such as Lobelia, will depend on knowledge of their distribution patterns and habitat preference in East Africa. To understand the distribution pattern and the habitat preference of Lobelia in five countries of East Africa, we conducted a literature review in the seven major vegetation regions . We also employed meander and patterned searches, which allowed greater opportunities for recording Lobelia species. Our results showed that the genus is distributed in all of the seven regions of the five countries with 54 taxa. The afro-montane forest region, with 41 taxa, is the richest in species diversity, followed by the Zambezian woodland region with 18 taxa. The semi-desert and desert region has the lowest number with only four taxa. The afro-alpine region has 15 taxa, although the region is the smallest by area. The herbaceous type was found in all regions, while the giant type has a clear preference for the afro-alpine and afro-montane forest regions. Future conservation for Lobelia should consider its habitat preference by, for example, focusing on the afro-alpine and afro-montane forest regions. This study will facilitate the setting of future conservation strategies for Lobelia.East Africa is one of the centres of distribution and diversity for Arabisalpina has a preference for stream-banks and cliffs in an altitude of 2800\u20134800 m, while T.glabra has a preference for grasslands in an altitude of 920\u20132650 m includes about 437 species. The genus is cosmopolitan, distributed in both temperate and tropical regions of Africa, America, Australia, New Zealand, Hawaii, Asia and other regions (Lobelia species (lobelias), with 37% of all lobelias distributed in Africa , Tanzania (T1\u20138), Uganda (U1\u20134), Rwanda and Burundi Mabb., Lobeliaburtiisubsp.telmaticola E.B.Knox and Lobeliaburtiisubsp.meruensis E.B.Knox were only found in areas within the T2 region, specifically on Mt. Meru, Mt. Hanang and Mt. Loolmalassin in Tanzania on the distribution of the lobelias. Therefore, they were not included in this study. The study area ranged from coastal regions to the alpine zones of high mountains with changes in the elevation gradient. To obtain a clear understanding of the Lobelia habitats and distribution patterns, seven vegetation regions were used , Uganda (U1\u20134), Tanzania (T1\u20138), Rwanda and Burundi. The other three countries in \u20137, Ugandsed Fig. . The vegsed Fig. . HoweverFlora of Tropical East Africa and voucher specimens in the herbarium of Wuhan Botanical Garden (HIB) that had been collected from 2009 to 2019.All lobelias described in the t Africa , Knox ant Africa , voucherTo maximise recording lobelias in traversed habitats, meander and patterned searches were useThe lobelias in the seven regions of the five countries are represented by 54 taxa including herbs, shrubs and sub-shrubs Table .Helichrysum Mill., Hypericum L. and Erica Boehm. The afro-alpine region extends to over 4900 m and is dominated by giant species of Dendrosenecio (Hauman ex Hedberg) B.Nord. and Lobelia. The giant lobelias include Lobeliastuhlmannii Schweinf. & E.A.Bruce, Lobeliadeckenii Hemsl., Lobeliagregoriana Baker f., Lobeliagregorianasubsp.satimae (R.E.Fr. & T.C.E.Fr.) E.B.Knox, Lobeliaburtii E.A.Bruce, L.burtiisubsp.telmaticola E.B.Knox, L.burtiisubsp.meruensis E.B.Knox, Lobeliabequaertii (De Wild.) Mabb., Lobeliawollastonii Baker f. and L.telekii. These species are mainly distributed in the upper alpine zone , particularly in the upland grassland and moorland on Mt. Elgon (Kenya/Uganda), Aberdare Ranges and Mt. Kenya. Recurring fires on the ericaceous belt created a buffer zone between the lower afro-alpine and the upper afro-montane forest regions. This buffer zone was observed to provide regeneration habitats for the herbaceous species L.minutula, L.lindblomii and L.holstii Afro-alpine region. In this study, the afro-alpine region includes the sub-alpine ericaceous zone and the afro-alpine zone. The sub-alpine ericaceous zone ranges from about 3000 m to 3800 m and is d Afro-alpe Tables . Besidesr. Table , inhabitCeltisafricana Burm.f., Senegalia Raf. spps., Vachellia (wight & Arn.) Kuntze spps., Ilex L. spps., Haplocoelumfoliolosum (Hiern) Bullock and Ficus L. spp., amongst others. These lowlands were well inhabited by nine herbaceous lobelias, which include Lobeliaerinus L., Lobeliatrullifoliasubsp.minor Thulin, Lobeliawelwitschii Engl. & Diels ex Diels, Lobeliasapinii De Wild., Lobeliafervenssubsp.recurvata (E.Wimm.) Thulin, Lobeliachireensis A.Rich., Lobeliainconspicua A.Rich, Lobeliaadnexa E.Wimm. and Lobeliahartlaubi Buchenau. The giant lobelias distributed in this vegetation include Lobeliamorogoroensis E. B. Knox & P\u00f3cs, Lobelialongisepala Engl. and L.giberroa Afro-montane forest region. The afro-montane forest region currently occurs in anthropogenically-fragmented patches in East Africa and has an altitudinal range of 0\u20133000 m . The lowa Tables , 2 at al Afro-mona Tables . An inte m Table . This spOleaeuropaeasubsp.africana (Mill.) P.S. Green., Juniperusprocera Hockst ex Endl., Prunusafricana (Hook.) Kalkman., Oldeaniaalpina (K. Schum.) Stapleton and Hageniaabyssinica (Faber-Langendoen) J.F.Gmel. However, non-native species have become fully naturalised in disturbed areas for timber production. The species include Grevillearobusta A.Cunn. ex R.Br., Casuarinaequisetifolia L., Cupressuslusitanica Lindl. Ex Parl., Pinuspatula Schiede & Deppe ex Schltdl., Eucalyptusglobulus Labill., Eucalyptussaligna Sm., Corymbiacitriodora (Hook.) K.D.Hill & Johnson, Corymbiamaculata (Hook.) K.D.Hill & Johnson, Fraxinuspennsylvanica f.colorata B.Boivin, Araucariacunninghamii Sweet ex Courtois and Acrocarpusfraxinifolius Arn.The highlands of the afro-montane forest region extend from 1500 m to 3000 m. These forests have recently been highly fragmented. They are similar in species composition across the East African countries. Dominant native species from other families found in this region include Lobeliagilgii Engl., Lobeliagraniticola E.Wimm., Lobeliatrullifolia Hemsl., Lobeliauliginosa E.Wimm., Lobeliadissecta M.B.Moss, Lobelianeumannii T.C.E.Fr., Lobeliaflaccidasubsp.granvikii (T.C.E.Fr.) Thulin, Lobeliamolleri Henriques., Lobeliarubescens De Wild., Lobeliaheyniana Spreng., L.minutula, Lobeliacymbalarioides Engl., Lobeliaduriprati T.C.E.Fr., L.holstii, Lobeliagoetzei Diels, Lobeliaovina E.Wimm., Lobeliabaumannii Engl., Lobeliafervens Thunb. and Lobeliaangolensis Engl. & Diels Drier savannah region. The drier savannah region is found in Kenya, Ethiopia and Somalia, where EA, and is dominated by alternating grasses with thorny bush-land and thicket. Although habitats in this region are different from others, some lobelias in this region are the same as in the areas of highland, wet and dry savannah and some even from the woodland. However, lobelias in this region are mostly restricted to the wet ground after rainfall and at the edges of wetlands in the marshy areas, streams and river banks, as well as tops of grass hills. The species include L.fervens, L.molleri, L.holstii, L.flaccidasubsp.granvikii, L.baumannii, L.goetzei, L.erinus and L.welwitschii (Table (4) Grassland region. Grassland region is the most common habitat in the ii Table . No gianCombretaceae R.Br., and Fabaceae Lindl. families dominate this region. Lobelias in this region include the herbaceous L.fervenssubsp.fervens, L.baumannii, L.goetzei, L.inconspicua, L.molleri, L.holstii, L.flaccidasubsp.granvikii, L.sapinii, L.chireensis, L.erinus and L.welwitschii (Table (5) Wetter savannah region. This region is widely distributed in Kenya, Tanzania and Uganda with altitudes from 0 m to 1250 m. Both Fabaceae, such as species of the genera Brachystegia Benth., Julbernardia Pellegr., Isoberlinia Craib & Stapf ex Holland and Uapaca Baill. Lobelia inhabits wet deciduous woodland habitats in this region. Herbaceous lobelias include L.fervenssubsp.fervens, L.chireensis, L.trullifoliasubsp.trullifolia, L.gilgii, L.sapinii, L.duriprati, L.goetzei, L.inconspicua, L.uliginosa, L.rubescens, Lobeliaheyneana Schult., L.adnexa, L.cymbalarioides, L.baumannii, L.erinus, L.angolensis and L.welwitschii (Table L.morogoroensis ((6) Zambezian woodland region. This region occurs in the southern part of Tanzania at altitudes ranging from 700 m to 1500 m. It is dominated by members of the family oroensis , which iL.fervenssubsp.recurvata, L.trullifoliasubsp.minor, L.welwitschii and L.chireensis (Table (7) Semi-desert and desert region. The hostile climate of this region forms semi-desert and desert vegetations in northern Kenya and southern Ethiopia. This region is characterised by thorny scattered trees and shrubs. Lobelias are distributed in muddy ditches edges and seasonal river banks. However, they are exceedingly rare and only appear in the seasonally-flooded ground or marshy edges of the freshwater wetlands. Species that are distributed in this region include is Table , Uganda (19), Burundi (9) and Rwanda (8) and those without the alpine regions (lowlands and Eastern Arc Mountains). The upland giant lobelias, except habitat .L.undzungwensis, L.morogoroensis, L.stricklandiae, L.ritabeaniana, L.sancta, L.lukwangulensis and L.longisepala. The Arc Mountains have evolved their distinctive lobelias, which are different from those of the upland mountains. The Arc Mountain biome, therefore, is a hotspot for the East Africa branched lobelias. The regions inhabited by lobelias have moist and warm habitats somewhat differentiated from the regions occupied by the inland giant lobelias. The Arc Mountain giant lobelias demonstrated a clear preference for moist and warm conditions within the mountains along the East Africa Coast, which is known as one of the world\u2019s biodiversity hotspots (The Eastern Arc Mountains (lowlands) form the easternmost blocks of East Africa . Althoughotspots .L.morogoroensis) to the sub-montane rainforests openings and also extend further to the cloud-forest summits (L.ritabeaniana, L.stricklandiae, L.undzungwensis, L.sancta and L.lukwangulensis (Table L.giberroa, which is found in the inland afro-montane forest, also grows on these Arc Mountains. Lobeliagiberroa in the Arc Mountains occupies habitats with similar physiognomic characteristics and similar associated plant species found elsewhere in the highland afro-montane forests (The Eastern Arc Mountains are separated from each other by lowland woodlands and savannah . The Arcis Table . Surpris forests . The EasEA Mountains. Without the present anthropogenic activities, the afro-montane forest would probably have existed as a single connected habitat (L.giberroa (L.bambuseti has been reported as being under threat (Land-use changes associated with deforestation and land degradation are major causes of biodiversity loss in East Africa . Current habitat . The habgiberroa . Therefor threat .EA have become centres for ecotourism. To facilitate tourist activities, roads and paths within the mountain have been built. The invasive species could follow the roadsides to reach different altitudes (L.holstii has expanded its range to almost 3900+ m on Mt. Kenya and dominated the roadsides in rocky disturbed places. Additionally, non-native tree species established in the forest plantation for timber production may pose a considerable threat (Moreover, the afro-montane forest and its environment are also threatened by invasive plants . Most ofltitudes . Accordie threat to nativEA Mountain biomes. The habitat preference of lobelias\u2019 hotspots is also facing the risk of both anthropogenic and climate change (Mountain forests are major water towers, biodiversity hotspots, species evolution refugia, eco-tourism locations, sources of wild foods and centres of plant genetics . For exae change . Habitate change . Therefoe change .Our results showed that lobelias are distributed in all of the seven vegetation regions in five countries of East Africa. The afro-montane forest region is the richest in species diversity, although it is not the largest by area. The herbaceous type has a preference for the lowland regions, while the giant type has a clear preference for the afro-alpine and afro-montane forest. Future conservation for the genus should consider the habitat preferences of lobelias."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-020-68518-w, published online 15 July 2020Correction to: Yuanhong He was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:G.H. designed the study and supervised the field work. G.H., J.G., Y.X., L.C. and Y.H. conducted the archaeological investigations. Y.C. and Y.H. analyzed the stone artifacts. G.H., C.X. and Z.L. analyzed the data. G.H. drafted the initial manuscript, which was revised by G.H. and J.G. All authors approved the final version."} +{"text": "Myotisnesopolus currently comprises two subspecies. The nominate subspecies (M.n.nesopolus) occurs on the Caribbean islands of Cura\u00e7ao and Bonaire, Netherlands Antilles, whereas M.n.larensis is known from mainland South America in northeastern Colombia and northwestern Venezuela. Our Maximum Likelihood phylogenetic analyses of cytochrome-b gene sequences recovered M.nesopolus as a paraphyletic group, with M.n.nesopolus and M.n.larensis as non-sister lineages. The haplotype network indicates that these two subspecies do not share any haplotypes and are in different evolutionary trajectories. Additionally, these two subspecies can be distinguished on the basis of qualitative and quantitative morphological traits. This pattern supports the recognition of M.nesopolus and M.larensis as full species. Our results also reveal that the assemblage of Caribbean Myotis do not form a monophyletic group. Caribbean species are phylogenetically close to mainland species from northern South America and Central America, suggesting that colonization of Caribbean islands happened multiple times. Myotis Kaup, 1829 comprises more than 120 species distributed worldwide, and is the most speciose genus of bats , were misidentifications of M.nesopolus, which was confirmed by Two subspecies of enezuela . LaVal , Carnegie Museum of Natural History , Smithsonian\u2019s National Museum of Natural History , and Museum of Texas Tech University . We examined the holotype of M.n.nesopolus (USNM 101849), two topotypes from Cura\u00e7ao , and nine specimens from Bonaire (Appendix M.n.larensis includes the holotype (AMNH 130709), and fifteen additional specimens from mainland Venezuela.Specimens of lus USNM 01849, twcyt-b, 1,140 bp, no gaps) sequences were conducted for the Neotropical assemblage of Myotis. A total of 122 sequences, including outgroups, were retrieved from GenBank and Myotisgracilis Ognev, 1927 as outgroups because they are sister to the Neotropical clade (see cyt-b sequences were performed with MEGA X (BIC), as implemented in JModelTest2 method method . To asseer model .M.n.nesopolus, M.n.larensis and other phylogenetically related population groups, we built a haplotype network (distribution of haplotypes by previously defined population groups) using the median-joining algorithm in the Network 4.6.1.3 software (To understand the population structure of software .M.n.nesopolus (N = 10), M.n.larensis (N = 9) and 14 species of Neotropical Myotis deposited in 11 collections in Brazil, Canada and United States to identify general trends of cranial size and shape variation among samples, and a discriminant function analysis (DFA), with a priori identification of samples, to compare skull size and shape of M.n.nesopolus (N = 9) and M.n.larensis (N = 9). For these analyses, we selected a subset of 11 craniodental dimensions representing different axes of the length and width of skull, rostrum, and mandible, as follows: greatest length of skull, including incisors (GLS), condylo-incisive length (CIL), mastoid breadth (MAB), braincase breadth (BCB), interorbital breadth (IOB), postorbital breadth (POB), breadth across canines (BAC), breadth across molars (BAM), maxillary toothrow length (MTL), molariform toothrow length (M1\u2013M3), and mandibular toothrow length (MAN). PCA and DFA analyses were run in R software in a previous study and other mainland putative species. Nevertheless, the phylogenetic relationship of Caribbean Myotis clade is not fully resolved, since a polytomy was recovered among M. sp. 3 from Honduras and the ancestral lineage of M.n.nesopolus and M. sp. 2 from Peru, and of M.n.larensis and M. sp. 1 from Ecuador. Similarly, a polytomy was recovered among M.atacamensis, M.martiniquensis and an ancestral lineage of M.dominicensis, M.nyctor and M. sp. 4 from Suriname accounted for 87% of the total craniometric variation, and represents overall skull size which represents overall skull shape. The distribution of M.n.larensis and M.n.nesopolus samples across size and shape axes in the discriminant analysis and skull width (IOB) were the most useful to discriminate samples ; dorsal fur Dresden-Brown with little contrast between bases and tips slightly lighter tips; ventral fur with blackish bases and Light-Buff tips ; dorsal fur strongly bicolored, with blackish bases (2/3) and Tawny-Olive tips (1/3); ventral fur with blackish bases and whitish tips is aligned in the toothrow and visible in labial view, and the occipital region is always rounded , morphologically similar to several Neotropical congeners. Ears are moderate in size (length 10\u201313 mm), and when laid forward extend halfway from eye to nostril. Antitragal notch is barely evident. Membranes are Mummy-brown. Fur on dorsal surface of uropatagium extends slightly past the knees. Plagiopatagium is attached to the foot at toes level by a broad band of membrane. Third metacarpal, tibia, and skull are long in relation to forearm , presence of sagittal crest, and dorsal fur longer and strongly bicolored. Considering the Myotis species that occurs in the northern South America, M.larensis differs from M.albescens by the absence of a fringe of hairs along the trailing edge of the uropatagium; from M.keaysi J. A. Allen, 1914, M.pilosatibialis LaVal, 1973, M.riparius Handley, 1960, and M.simus Thomas, 1901 by the long silky dorsal fur strongly bicolored. Myotislarensis can also be distinguished from M.simus by the plagiopatagium broadly attached at base of the toes. Myotislarensis differs from M.diminutus Moratelli & Wilson, 2011 by its larger cranial dimensions and dorsal fur strongly contrasting; from M.handleyiM.oxyotus by having a smaller skull, less steeply sloping frontals and strongly contrasting dorsal fur. Myotislarensis differs from M.attenboroughiM.clydejonesiMyotislarensis differs from M.caucensis Allen, 1914 by its smaller skull and strongly contrasting dorsal fur. Myotislarensis can be distinguished from M.cf.nigricans from northern South America and Grenada (N = 1) in the same clade , M.ruber , M.nigricans , M.levis , M.chiloensis , M.oxyotus , M.atacamensis , M.nesopolus Miller, 1900, M.simus Thomas, 1901, M.dinellii Thomas, 1902, M.dominicensis Miller, 1902, M.caucensis Allen, 1914, M.keaysi J.A. Allen, 1914, M.riparius Handley, 1960, M.elegans Hall, 1962, M.larensis LaVal, 1973, M.martiniquensis LaVal, 1973, M.pilosatibialis LaVal, 1973, M.nyctor LaVal & Schwartz, 1974, M.diminutus Moratelli & Wilson, 2011, M.lavaliM.izecksohniM.handleyiM.midastactus Moratelli & Wilson, 2014, M.clydejonesiM.attenboroughiM.bakeri Moratelli et al., 2019, and M.armiensis Carri\u00f3n-Bonilla & Cook, 2020. However, our results indicate that there are at least four haplogroups that might correspond to undescribed species. This scenario confirms the Neotropical region as a highly diverse region for Myotis.With the recognition of is sensu are curr"} +{"text": "Polyommatus (Agrodiaetus) damone species complex comprises from 5 to 8 species distributed in southeastern Europe and southern Siberia. Here we used chromosomal and DNA-barcode markers in order to test the taxonomic hypotheses previously suggested for this complex. We revealed that all taxa within this group demonstrate chromosomal stasis and share the same or very similar haploid chromosome number (n = 66 or n = 67). This finding is unexpected since the karyotypes are known to be very diverse and species-specific within the other taxa of the subgenus Agrodiaetus H\u00fcbner, 1822. Analysis of the mitochondrial gene COI revealed six diverged clusters of individuals within the complex. Each cluster has a specific geographic distribution and is characterized by distinct morphological features in the wing pattern. The clusters mostly correlate with traditionally recognized species. As a result of our study, we describe a new subspecies P. (A.) iphigenideszarmitanussubsp. nov. from Uzbekistan and Tajikistan and show that the taxon originally described as Lycaenakindermannivar.melania Staudinger, 1886 represents a subspecies P. (A.) iphigenidesmelanius . Polyommatus (A.) samusi Korb, 2017 (syn. nov.) and P. (A.) melaniuskomarovi Korb, 2017 (syn. nov.) are considered here as junior subjective synonyms of P. (A.) iphigenidesiphigenides .The Polyommatus (Agrodiaetus) damone species complex is a monophyletic group damone complex in order to test the taxonomic hypotheses previously suggested for this group (see the references above).Here we analyzed karyotypes and mitochondrial DNA-barcodes of all species of the P. (A.) damonewalteri Dantchenko et Lukhtanov, 1993, P. (A.) damonefabiani B\u00e1lint, 1997 and P. (A.) damonebogdoolensis Dantchenko et Lukhtanov, 1997 are not considered in this paper since neither chromosomal nor molecular data are available. This also applies to P. (A.) carmonaltaiensis , recently treated by P. (A.) damone complex distributed in Mongolia, Altai and southwestern Siberia. Morphologically they are close to other populations of P.damone or to P.mediator Dantchenko et Churkin, 2003. Their study will become possible in the future as soon as the material suitable for molecular and chromosomal analyses becomes available.The taxa COI barcodes were studied. COI sequences were obtained from 44 specimens representing the P.damone species group and from two samples [P.damon and P.icarus ] which were selected as outgroup using protocols described in Lepidoptera and Biodiversity (MGCL), Florida Museum of Natural History, University of Florida, Gainesville, Florida, USA. Photographs of these specimens, as well as collecting data are available in the Barcode of Life Data System (BOLD), projects Butterflies of Palearctic (BPAL) and Butterflies of Palearctic Part B (BPALB) at http://www.boldsystems.org/.Standard COI sequences > 200] using the program tracer v1.7.1 (http://tree.bio.ed.ac.uk/software/figtree/).Sequences were aligned using the BioEdit software and editr v1.7.1 . The firMI) and metaphase II (MII) were examined using an original two-phase method of chromosome analysis (ca (circa) means that the count was made with an approximation due to an insufficient quality of preparation or overlapping of some chromosomes or bivalents.Karyotypes were studied in 16 adult males representing four species Table and wereanalysis , 2008. ALeica DM2500 light microscope equipped with HC PL APO 100\u00d7/1.44 Oil CORR CS lens and S1/1.4 oil condenser head was used for bright-field microscopy analysis. Leica DM2500 light microscope equipped with HC PL APO 100\u00d7/1.40 OIL PH3 lens was used for phase-contrast microscopy analysis.P. (A.) damone species complex damone (I) and P. (A.) karatavicus Lukhtanov, 1990 (V) were highly supported. The lineage of P. (A.) phyllides (VI) and the lineage (II) had medium support. The clusters III [P. (A.) iphigenidesiphigenides + P. (A.) iphigenidesmelanius ] and VI (P. (A.) iphigenideszarmitanus subsp. nov.) appeared on the tree as two distinct, not closely related paraphyletic taxa.Phylogenetic analysis revealed six clusters of closely related individuals within the lex Fig. . Of thesP. (A.) damonedamone, of a single male of P. (A.) damonetanais Dantchenko et Pljushtch, 1993, of two males of P. (A.) iphigenidesiphigenides, of three males of P. (A.) iphigenidesmelanius, of a single male of P. (A.) phyllidesphyllides, of two males of P. (A.) phyllidesaskhabadicus and four males of P. (A.) iphigenideszarmitanus subsp. nov. revealed the same haploid chromosome number n = 66 or n = 67 in all studied taxa damone species complex demonstrate chromosomal stasis and share the same or very similar haploid chromosomal number (n = 66 or n = 67). This result is unexpected since the karyotypes are known to be very diverse and species-specific in the subgenus Agrodiaetus.It has been found that all taxa within Agrodiaetus. Species of this subgenus exhibit one of the highest ranges in chromosome numbers in the animal kingdom (Agrodiaetus haploid chromosome numbers (n) range from n = 10 in P. (A.) caeruleus to n = 134 in P. (A.) shahrami . The gen n = 226 . Additioome size and variome size . These dome size , b.P. (A.) damone species complex represents an exception. In this group divergence in several phylogenetic lineages was not accompanied by changes in karyotypes, and the chromosome number n = 66-67 is the synapomorphic character for the species of the group.The P. (A.) damone. Cluster 2 includes specimens from NE Kyrgyzstan, SE Kazakhstan and SW Mongolia and corresponds to P. (A.) juldusus + P. (A.) mediator. Cluster 3 includes specimens from western and southern Kyrgyzstan, southern Kazakhstan and Tajikistan and corresponds to P. (A.) iphigenidesiphigenides + P. (A.) iphigenidesmelanius. Cluster 4 includes specimens from West Hissar in Uzbekistan and western Tajikistan and corresponds to P. (A.) iphigenideszarmitanus subsp. nov. which will be described below. Cluster 5 includes specimens from Karatau Mts in Kazakhstan and corresponds to P. (A.) karatavicus. Cluster 6 phyllides.The DNA-barcode clusters revealed in our study correspond well to traditionally recognized species and certain specific geographic areas Figs , 4. ClusP.phyllides) is sympatric with cluster 2 (=P.juldusus) in northern Kyrgyzstan and southeastern Kazakstan, with cluster 3 (=P.iphigenidesiphigenides+P.iphigenidesmelanius) in Kyrgyzstan and Tajikistan, with cluster 4 (=P.iphigenideszarmitanus) in Uzbekistan and western Tajikistan, with cluster 5 (=P.karatavicus) in Karatau Mts in Kazakhstan (Cluster 6 (=P.damone), 2 (P.juldusus and P.mediator) and 5 (P.karatavicus) (see Taxonomic conclusions below). P. (A.) mediator was described as a species which is intermediate between P. (A.) damone and P. (A.) juldusus, but more similar to P. (A.) juldusus due to specific white pubescence of the costal area of the forewings (P. (A.) juldususkasachstanus, and as a sister clade to P. (A.) juldususjuldusus + juldususkirgisorum.P. (A.) We follow previous research in interorewings . This coP. (A.) mediator and P. (A.) damone in Mongolia as it was reported or supposed earlier (Up to our knowledge there are no data on sympatry of earlier .Polyommatus (Agrodiaetus) iphigenides is highly polymorphic with regard to the black suffusion on the wing upperside and the marginal and submarginal part of the wing underside in males as well as the white streak on hindwings in both sexes. In extreme cases, the suffusion can be practically absent resembling the upperside in P.damone or may extend almost to the discal spot which is observed as a fixed feature in two other taxa, P.iphigenidesmelanius and P.juldususkirgisorum. The white streak is also very variable from clear visibility to complete absence. The taxa P. (A.) samusi Korb, 2017 (syn. nov.) and P. (A.) melaniuskomarovi Korb, 2017 (syn. nov.) are mainly described on the base of such extreme forms of the same population. Therefore, we consider these taxa as junior subjective synonyms of iphigenidesiphigenides.P. (A.) Lycaenakindermanni var. Melania Staudinger, 1886. For a long time, due to lack of material it had been considered to be a melanized form of P. (A.) iphigenidesiphigenides (e.g. P. (A.) melanius with a local, nearly dot-like distribution in the border area between southwestern Kyrgyzstan and eastern Tajikistan in the Kyzylsu/Surkhob River basin (P. (A.) iphigenides and P. (A.) melanius are identical or differ by non-fixed 1\u20132 nucleotide substitutions. The main feature of P. (A.) melanius, a wide dark marginal border on the fore- and hindwings, is quite stable for the diagnosis of the taxon; however, the tendency towards such a wide border is expressed in different populations of P. (A.) iphigenides, too. Therefore, this trait can be hardly considered a species-specific character. Here we argue that P. (A.) melanius is rather a subspecies P. (A.) iphigenides than a species. However, this is not a final conclusion. There is indirect evidence in favour of a possible species status of P. (A.) melanius, e.g. the distribution areas of P. (A.) iphigenidesiphigenides and P. (A.) iphigenidesmelanius almost touch each other, and an intergradation zone would be expected between them. However, such a zone is still unknown, and specimens of P. (A.) iphigenidesiphigenides and P. (A.) iphigenidesmelanius from very close localities are clearly differentiated. We suppose that genome-wide analysis may be useful to verify the taxonomic status of P. (A.) iphigenidesmelanius.Cluster 3 also includes the taxon described as des e.g. . But in er basin . We founP.ipigenidesiphigenides, whereas with regard to mitochondrial DNA it is close to sympatric species P.phyllides which is morphologically very different. In our opinion, two alternative evolutionary scenarios can explain this pattern.Morphologically this group is close to P.iphigenideszarmitanus) and the lineage 6 (P.phyllides) are sister species which recently evolved from a common ancestor by means of sympatric speciation.The cluster 4 (P.iphigenides) and cluster 4 (P.iphigenideszarmitanus) are sister taxa evolved in allopatry; therefore, they share an ancestral type of the wing pattern and coloration, although differentiated with respect to DNA barcodes. The similarity between completely sympatric cluster 4 (P.iphigenideszarmitanus) and lineage 6 (P.phyllides) is a result of ancient mitochondrial introgression.Cluster 3 (Polyommatus (Agrodiaetus) . TherefoP.phyllides) is a distinct species, since it is a monophyletic lineage iphigenidesiphigenides, P. (A.) iphigenidesmelanius, P. (A.) iphigenideszarmitanus, P. (A.) karatavicus and P. (A.) juldusus.There is no doubt that the cluster 6 .Fig. , male, BACATTATATTTTATTTTTGGAATTTGAGCAGGAATAGTAGGGACATCCCTAAGAATTTTAATCCGTATAGAATTGAGAACT CCTGGATCCTTAATTGGAGACGATCAAATTTATAATACTATTGTTACAGCCCATGCATTTATTATAATTTTTTTTATAGTTA TACCTATTATAATTGGGGGATTTGGTAATTGATTAGTTCCTTTAATATTAGGAGCACCTGATATAGCCTTCCCCCGATTAAA TAATATAAGATTCTGATTATTACCGCCATCATTAATACTACTAATTTCCAGAAGAATTGTAGAAAATGGAGCAGGAACAGGA TGAACAGTTTACCCCCCACTTTCATCTAATATTGCACATAGAGGATCATCTGTAGATTTAGCAATTTTCTCTCTTCATTTAG CAGGAATTTCTTCAATTTTAGGAGCAATTAATTTTATTACAACTATTATTAACATACGGGTAAATAATTTATCATTTGATCA AATATCATTATTTATTTGAGCAGTAGGAATTACAGCATTATTATTACTTTTATCTTTACCTGTATTAGCTGGAGCAATTACC ATATTATTAACAGATCGAAACCTTAATACCTCATTCTTTGACCCAGCTGGTGGGGGAGATCCAATTTTATATCAACATTTA.40.40\u00b0N, 66.69\u00b0E, 1300 m, 11\u201313 June 1994, V. Lukhtanov leg. 2 males: Uzbekistan, Qashqadaryo Region (old spelling: Kashkadarya Region), Hissar Range (west), near Tamshush village, 38.98\u00b0N, 67.35\u00b0E, 1800 m, 18\u201320 June 1994, V. Lukhtanov leg. 20 males: Uzbekistan, Qashqadaryo Region (old spelling: Kashkadarya Region), Hissar Range (west), near Tamshush village, 38.98\u00b0N, 67.35\u00b0E, 1800 m, 5\u20137 July 1994, V. Lukhtanov leg. 11 males, 2 females: Uzbekistan, Surxondaryo Region (old spelling: Surkhandarya Region), Hissar Range (west), Sangardak, 38.55\u00b0N, 67.50\u00b0E, 1600 m, 2 July 1994, V. Lukhtanov leg. 60 males, 21 females: Uzbekistan, Samarqand Region, Zeravshansky Range, Aman-Kutan, 1800 m, 39.27\u00b0N, 66.90\u00b0E, 7 July 1994, V. Lukhtanov leg. 13 males: Tajikistan, Sughd Region, Zeravshansky Range, Padzhrud village, 39.37\u00b0N, 68.03\u00b0E, 1300 m, 17 males, 13 males, 10 June 1994. All above paratypes are deposited in the Zoological Institute of the Russian Academy of Science (St. Petersburg). 5 males: Uzbekistan, [Jizzakh region], Usmat vic., 1700 m, 30.06.1988, V. Tshikolovets leg., in State Darwin Museum, Moscow. 15 males: [Uzbekistan], Aman-Kutan near Samarqand, 20 June 1938, A. Tsvetaev leg., in State Darwin Museum, Moscow. 26 males, 1 female: [Tajikistan], Hisar-Alai, Zeravshansky Range, Farob, 2000 m, 4 July 1998, G.D. Samodurov leg., in State Darwin Museum, Moscow. 1 female: Tajikistan, West Hissar, Nofin lake, 2400, 17 July 1993, S. Churkin leg., in State Darwin Museum, Moscow. 32 males: [Uzbekistan], Aman-Kutan near Samarqand, 15\u201325 June 1938, A. Tsvetaev leg., in Zoological Museum Moscow University, Moscow (ZMMU). 7 males: [Uzbekistan], Aman-Kutan near Samarqand, 20\u201323 June 1938, G.Pashin leg., in ZMMU. 2 males: [Uzbekistan], Aman-Kutan near Samarqand, 27 July and 5 August 1937, A. G. Pashin leg., in ZMMU. 3 females: [Uzbekistan], Aman-Kutan near Samarqand, 15\u201326 June 1938, A. Tsvetaev leg., in ZMMU. 8 males: Tajikistan, West Hissar, Khazorchashma lake, 2800, 26 July 1993, S. Churkin leg.; 1 female: Tajikistan, West Hissar, Nofin lake, 2400, 17 July 1993, S. Churkin leg., in coll. Churkin . 2 males, 1 female: Uzbekistan, West Hissar, Boysun Mts, Mochay, 1500 m, 26 June 1980, V. Tuzov leg., in coll. Tuzov (Moscow). 10 males, 1 female: [Uzbekistan], Aman-Kutan near Samarqand, 19\u201323 June 1938, A. Tsvetaev leg., in coll. Sochivko A. (Moscow). 10 males, 1 female: [Tajikistan], Hissar-Alai, Zeravshansky Range, Farob, 2000 m, 4 July 1998, L. Nikolaevsky leg., in coll. V. Kalinin, Moscow.39 males, 14 females: Uzbekistan, Samarqand Region, Nuratau Mts, near Zarmitan village, ForewingMales. length 15\u201317 mm.Upperside: Ground color bright glossy milky blue with narrow black marginal line, marginal part of forewings and hindwings dusted with black scales, discal strokes may be present or absent, veins darkened, costal area of the forewings white, hindwings with antemarginal spots, fringe white.Underside: Forewing ground color light grey, submarginal row blurred, but clear visible; discoidal strokes black, bordered with white; postdiscal rows of black spots bordered with white, basal black spots absent; hindwing ground color light grey, basal area with strong greenish blue suffusion between wing root and basal spots; basal spots small, bordered with white, discal stroke less prominent than on forewings; postdiscal row of black spots bordered with white, submarginal and antemarginal marking strong and clear visible; submarginal row bordered distally with reddish lunules, more pronounced to anal end of row; white streak not contrasting, often hardly noticeable or absent at all, fringes pale grayish.Genitalia. The male genitalia have a structure typical for other species of the subgenus Agrodiaetus . The new species always has black dots of the basal row , while in another species they are reduced.The new subspecies is distinguished phenotypically from the most similar des Figs , 6c, d bPolyommatusiphigenideszarmitanus can be distinguished from P.iphigenidesiphigenides by using molecular markers from the COI gene. These mitochondrial diagnostic characters are in the following positions in the COI barcode region: adenine (A) in position 22, cytosine (C) in position 132, guanine (G) in position 180, cytosine (C) in position 286, guanine (G) in position 468, guanine (G) in position 468, and guanine (G) in position 627.The main differences between the species are still in the molecular characters. P.phyllides by milky blue (not greenish blue) wing upperside and white pubescence of the costal area of the forewings in males and by light grey color of the wing underside (P.phyllides has specific warm pinkish grey color of the wing underside). It also differs from P.phyllides by diagnostic nucleotide guanine (G) in position 627 of the COI barcode region.The new subspecies differs from sympatric (syntopic and synchronous) Fig. . Uzbekistan: West part of the Hissar Range, Zeravshan Mts, Nuratau Mts, Boysun (= Baisuntau) Mts. Tajikistan: west part of the Zeravshan valley and Zeravshansky Range, West Hisar Range.P. (A.) phyllides, but on average about one decade earlier. Host plant is preliminary determined as Hedysarum sp. (Fabaceae).Stony steppe and dry meadows from 1200 up to 2800 m alt. Flight period from late May to first decade of August in a single generation. The new subspecies flies syntopically and synchronously with the second generation of zarmitanus is an adjective of the masculine gender. This name originates from Zarmitan, the village in Uzbekistan.The name P. (A.). altaiensis with subspecies P. (A.) altaiensisaltaiensis, P. (A.) altaiensisbogdoolensis Dantchenko et Lukhtanov, 1997, P. (A.). altaiensismediator and P. (A.) altaiensishabievi Yakovlev, 2004 damone P. (A.) damonepljushtchi P. (A.) damonetanais Dantchenko et Pljushtch, 1993P. (A.) damoneirinae Dantchenko, 1997P. (A.) damonedamone P. (A.) damonealtaicus P. (A.) damonewalteri Dantchenko et Lukhtanov, 1993P. (A.) damonebogdoolensis Dantchenko et Lukhtanov, 1997P. (A.) damonefabiani B\u00e1lint, 1997P. (A.) mediator Dantchenko et Churkin, 2003 P. (A.) juldusus P. (A.) juldususjuldusus P. (A.) juldususkirgisorum Lukhtanov et Dantchenko, 1994 P. (A.) juldususkasachstanus Lukhtanov et Dantchenko, 1994P. (A.) juldususrueckbeili Forster, 1960P. (A.) juldusustianchinensis Eckweiler, 2013P. (A.) iphigenides P. (A.) iphigenidesiphigenides P. (A.) iphigenidesmelanius P. (A.) iphigenideszarmitanus subsp. nov.P. (A.) karatavicus Lukhtanov, 1990P. (A.) phyllides P. (A.) phyllidesphyllides P. (A.) phyllidesaskhabadicus P. (A.) phyllideskentauensis Lukhtanov, 1990P. (A.) phyllidesurumbash Churkin et Zhdanko, 2008"} +{"text": "Leptobrachella is described from Guizhou Province, China. Molecular phylogenetic analyses support the new species as an independent lineage deeply nested in the Leptobrachella clade. The new species is distinguished from its congeners by a combination of the following morphological characters: body size medium ; dorsal skin shagreened, some of the granules forming longitudinal short skin ridges; tympanum distinctly discernible, slightly concave; supra-axillary, femoral, pectoral and ventrolateral glands distinctly visible; absence of webbing and lateral fringes on fingers; toes with narrow lateral fringes but without webbing; heels overlapping when thighs are positioned at right angles to the body; tibia-tarsal articulation reaching the middle of eye when leg stretched forward. The discovery highlighted the underestimated species diversity in the Leptobrachella toads in southwestern China.A new species of the Asian leaf litter toad genus Leptobrachella Smith, 1925 are widely distributed from southern China west to northeastern India and Myanmar, through mainland Indochina to peninsular Malaysia and the island of Borneo and L.bourreti from Yunnan and Guangxi; L.eos , L.nyx , L.pelodytoides , L.tengchongensis , L.yingjiangensis , L.feii , L.flaviglandulosa , and L.niveimontis from Yunnan; L.laui and L.yunkaiensis Wang, Li, Lyu & Wang, 2018 from Guangdong and Hong Kong; L.liui from Fujian, Jiangxi, Guangdong, Guangxi, Hunan, and Guizhou; L.oshanensis from Gansu, Sichuan, Chongqing, Guizhou, and Hubei; L.purpuraventra , L.bijie , L.chishuiensis , and L.suiyangensis from Guizhou; L.purpurus , L.ventripunctata from Guizhou and Yunnan; L.mangshanensis from Hunan; and L.sungi , L.maoershanensis , L.shangsiensis , and L.wuhuangmontis from Guangxi. Among them, ten Leptobrachella species occur in Guizhou Province, China, highlighting the high species diversity of the genus in this region.The Asian leaf litter toads of the genus f Borneo . Many sp83 e.g., , 2012, b species but a se species . To dateLeptobrachella from northwest Guizhou Province, China. Molecular phylogenetic analyses, morphological comparisons, and bioacoustics data consistently indicated these specimens as an undescribed species of Leptobrachella. We describe it herein as a new species.In recent years, we collected some specimens of Chengdu Institute of Biology, Chinese Academy of Sciences .Five adult males of the new species were collected on 16 May 2020 from Lengshuihe Nature Reserve, Jinsha County, Guizhou Province, China and Bayesian Inference (BI) methods, implemented in PhyML v. 3.0 ;FL foot length (distance from tarsus to the tip of the fourth toe);HDL head length (distance from the tip of the snout to the articulation of jaw);HDW head width (greatest width between the left and right articulations of jaw);HLL hindlimb length (distance from tip of fourth toe to vent);IND internasal distance ;IOD interorbital distance (minimum distance between the inner edges of the upper eyelids);LAL length of lower arm and hand ;LW lower arm width (maximum width of the lower arm);ML manus length ;SL snout length (distance from the tip of the snout to the anterior corner of the eye);SVL snout-vent length (distance from the tip of the snout to the posterior edge of the vent);TEY tympanum-eye distance (distance from anterior edge of tympanum to posterior corner of eye);TFL length of foot and tarsus ;THL thigh length (distance from vent to knee);TL tibia length (distance from knee to tarsus);TW maximal tibia width;TYD maximal tympanum diameter;UEW upper eyelid width (greatest width of the upper eyelid margins measured perpendicular to the anterior-posterior axis).SVL was calculated and then all of the data were log-transformed for the following morphometric analyses. Mann-Whitney U tests were conducted to test the significance of differences on morphometric characters between Leptobrachellajinshaensis sp. nov., L.bijie and L.chishuiensis. The significance level was set at 0.05. Furthermore, principal component analyses (PCA) were conducted to highlight whether the different species were separated in morphometric space. Due to only the measurements SVL, HDL, HDW, SL, IND, IOD, ED, TYD, TEY, LAL, ML, TL, HLL, and FL of male L.bijie being available from In order to reduce the impact of allometry, the correct value from the ratio of each character to Leptobrachellajinshaensis sp. nov. was also compared with all other congeners of Leptobrachella based on morphological characters. Comparative morphological data were obtained from literatures , being at the same level with or higher than that between some pairs of substantial species, such as L.bijie vs. L.chishuiensis (2.1%), and L.chishuiensis vs. L.alpina , the first principal component axis could separate L.jinshaensis sp. nov. from L.bijie and L.chishuiensis than L.bijie , and has lower dominant frequency (4525 \u00b1 0.065 Hz) than L.bijie (4780.4 \u00b1 76.5 Hz) and L.chishuiensis (6064\u20136284 H). Each call of L.jinshaensis sp. nov.has two kinds of notes, while each call of L.chishuiensis only has one kind of note.In total, 109 advertisement calls of Taxon classificationAnimaliaAnuraMegophryidae253F2320-A11B-512C-B8FF-90CC36AA0F70http://zoobank.org/C2982600-D9EF-46C1-A539-CC1151444B1827.536944\u00b0N, 105.999166\u00b0E, ca. 770 m a. s. l.), Guizhou Province, China by Shi-Ze Li on 16 May 2020.CIBJS20200516004, adult male , vomerine teeth absent, tubercles on eyelids, and the anterior tip of snout with a vertical white bar.Leptobrachellajinshaensis sp. nov. can be distinguished from its congeners by a combination of the following characters: body of medium size ; dorsal skin shagreened, some of the granules forming longitudinal short skin ridges; tympanum distinctly discernible, slightly concave; supra-axillary, femoral, pectoral, and ventrolateral glands distinctly visible; absence of webbing and lateral fringes on fingers; toes with narrow lateral fringes and without webbing; heels overlapping when thighs positioned at right angles to the body; tibia-tarsal articulation reaching the middle eye when leg stretched forward.Figs , 5. Adult male. SVL in 31.1 mm. Head length slightly longer than head width (HDL/HDW 1.02); snout slightly protruding, projecting slightly beyond margin of the lower jaw; nostril closer to snout than eye; canthus rostralis gently rounded; loreal region slightly concave; interorbital space \ufb02at, interorbital distance slightly longer than internarial distance; pineal ocellus absent; vertical pupil; eye diameter slightly shorter than snout length; tympanum distinct, rounded, and slightly concave, diameter smaller than that of the eye (TMP/ED 0.61); upper margin of tympanum in contact with supratympanic ridge; vomerine teeth absent; tongue notched behind; supratympanic ridge distinct, extending from posterior corner of eye to supra-axillary gland.Forelimbs slender, 48.9% of snout-vent length; tips of fingers rounded, slightly swollen; relative finger lengths I < II <= IV < III; absence of webbing; nuptial pad and subarticular tubercles absent; inner palmar tubercle large, rounded separated from the smaller, round outer palmar tubercle.Hindlimbs slender, tibia slightly longer than thigh length and 48.4% of snout-vent length; heels overlapping when thighs are positioned at right angles to the body, tibiotarsal articulation reaching middle eye when leg stretched forward; relative toe lengths I < II < V < III < IV; tips of toes round, slightly dilated; subarticular tubercle at the articulations of the toes absent; toes without webbing; lateral fringes narrow on all toes; inner metatarsal tubercle present, large, oval, outer metatarsal tubercle absent.Dorsal surface shagreened and granular, some of the granules forming short longitudinal folds dorsally on the flank; ventral skin smooth; dense tiny granules present on ventral surface of thigh and tibia; pectoral gland and femoral gland white, oval, distinctly visible. Ventrolateral gland distinctly visible and forming an incomplete line.Dorsum brown, with small, distinct darker brown markings and spots, and irregularly dispersed light orange speckles. A dark brown inverted triangular pattern between anterior corners of eyes. Tympanum brown, a dark brown bar above tympanum, and a dark brown bar under the eye, distinct black supratympanic line present; transverse dark brown bars on dorsal surface of limbs; distinct dark brown blotches on \ufb02anks from groin to axilla, longitudinally in two rows; elbow and upper arms with dark bars and distinct coppery orange colouration; fingers and toes with distinct dark bars. Ventral surface of throat cream white, chest, and belly cream yellow with purple speckling, and on \ufb02anks presence of distinct nebulous greyish speckling; ventral surface of limbs grey purple. Supra-axillary gland, femoral, pectoral, and ventrolateral glands white Fig. .Dorsum of body and limbs fade to brown copper; transverse bars on limbs become more distinct. Ventral surface of body and limbs fade to cream white. Supra-axillary, femoral, and pectoral glands fade to creamy yellow Fig. .Measurements of adult specimens were presented in Tables Leptobrachellajinshaensis sp. nov. were recorded in Lengshuihe Nature Reserve, Jinsa County, Guizhou Province, China on 16 May 2020 between 21:00\u201322:00. The call description is based on recordings of the holotype CIBJS20200516004 under a stone nearby a stream, and the ambient air temperature was 20 \u00b0C. The sonograms and waveforms of the new species are shown in Fig. In total, 109 advertisement calls of Adult males with a comparatively large single subgular vocal sac and nuptial pads and spines absent.SVL 29.7\u201331.2, n = 5), Leptobrachellajinshaensis sp. nov. is larger than L.aerea (25.1\u201328.9), L.alpina (24.0\u201326.4), L.applebyi (19.6\u201322.3), L.ardens (21.3\u201324.7), L.baluensis (14.9\u201315.9), L.bidoupensis (18.5\u201325.4), L.bondangensis (17.8), L.brevicrus (17.1\u201317.8), L.crocea (22.2\u201327.3), L.feii (21.5\u201322.8), L.flaviglandulosa (23.0\u201327.0), L.fusca (16.3), L.isos (23.7\u201327.9), L.itiokai (15.2\u201316.7), L.juliandringi (17.0\u201317.2), L.khasiorum (24.5\u201327.3), L.laui (24.8\u201326.7), L.maculosa (24.2\u201326.6), L.mangshanensis (22.22\u201327.76), L.maura (26.1), L.melica (19.5\u201322.8), L.mjobergi (15.7\u201319.0), L.natunae (17.6), L.niveimontis (22.5\u201323.6), L.parva (15.0\u201316.9), L.palmata (14.4\u201316.8), L.pallida (24.5\u201327.7), L.petrops (23.6\u201327.6), L.pluvialis (21.3\u201322.3), L.purpurus (25.0\u201327.5), L.rowleyae (23.4\u201325.4), L.serasanae (16.9), L.tengchongensis (23.9\u201326.0), L.ventripunctata (25.5\u201328.0), and L.yingjiangensis (25.7\u201327.6); and smaller than L.eos (33.1\u201334.7), L.gracilis (34.3\u201339.0), L.marmorata (32.3\u201338.0), L.nahangensis (40.8), L.platycephala (35.1), L.sungi (48.3\u201352.7), L.tamdil (32.0), and L.zhangyapingi (45.8\u201352.5).Measurements were given in mm. In male, by body size moderate in male .By the presence of supra-axillary and ventrolateral glands, Leptobrachellajinshaensis sp. nov. differs from L.crocea and L.tuberosa (vs. invisible in the latter).By tympanum distinctly visible, Leptobrachellajinshaensis sp. nov. differs from L.aerea, L.botsfordi, L.firthi, L.crocea, L.isos, L.pallida, L.petrops, and L.tuberosa (vs. lacking in the latter).By having black spots on \ufb02anks, Leptobrachellajinshaensis sp. nov. differs from L.aerea, L.alpina, L.applebyi, L.bidoupensis, L.bijie, L.botsfordi, L.bourreti, L.chishuiensis, L.crocea, L.eos, L.feii, L.firthi, L.fuliginosa, L.isos, L.khasiorum, L.lateralis, L.laui, L.liui, L.macrops, L.mangshanensis, L.maoershanensis, L.marmorata, L.melica, L.minima, L.nahangensis, namdongensisL , L.niveimontis, L.nokrekensis, L.nyx, L.pluvialis, L.pluvialis, L.puhoatensis, L.purpurus, L.purpuraventra, L.pyrrhops, L.sabahmontaus, L.shangsiensis, L.suiyangensis, L.tengchongensis, L.tuberosa, L.ventripunctata, L.wuhuangmontis, L.yingjiangensis, L.yunkaiensis, and L.zhangyapingi (vs. webbing rudimentary in the latter); and differs from L.flaviglandulosa and L.pelodytoides (vs. webbing present in the latter).By toes without webbing, Leptobrachellajinshaensis sp. nov. differs from L.aerea, alpinaL , L.firthi, L.laui, L.liui, L.khasiorum, and L.yunkaiensis (vs. wide in the latter); and differs from L.kalonensis, L.macrops, L.minima, L.marmorata, L.namdongensis, L.nyx, L.oshanensis, L.pyrrhops, L.rowleyae, and L.tuberosa (vs. lacking in the latter).By toes with narrow lateral fringes, Leptobrachellajinshaensis sp. nov. differs from L.applebyi, L.bidoupensis, L.kalonensis, L.melica, L.minima, L.nahangensis, L.shangsiensis, and L.tadungensis , and L.bourreti , L.fuliginosa (dorsum smooth with fine tubercles), L.liui (dorsum with round tubercles), L.macrops (dorsum roughly granular with large tubercles), L.maoershanensis (dorsum shagreened with tubercles), L.minima (dorsum smooth), L.nyx (dorsum with round tubercles), L.nokrekensis , L.pelodytoides , L.tamdil , L.tuberosa (dorsum very tuberculate), L.yunkaiensis (dorsum with raised warts), and L.wuhuangmontis .By dorsal surface shagreened and granular, lacking enlarge tubercles or warts, Leptobrachellajinshaensis sp. nov. differs from L.applebyi , L.ardens , L.bidoupensis , L.botsfordi , L.crocea , L.fuliginosa , L.heteropus , L.maculosa , L.melanoleuca , L.melica , L.pallida , L.pyrrhops , L.rowleyae , L.sola , L.tadungensis and L.tuberosa . The call of the new species appears to have lower frequency compared to the calls attributed to L.aerea , L.isos , L.marmorata , L.pelodytoides , L.ventripunctata and L.yingjiangensis .By having higher dominant frequency , Leptobrachellajinshaensis sp. nov. differs from L.aerea (16\u201328 ms), L.bidoupensis (308\u2013400), L.botsfordi (239\u2013303 ms), L.firthi (18\u201324 ms), L.fuliginosa (51\u201380 ms), L.isos (31\u201338 ms), L.maculosa (889\u2013907 ms), L.marmorata (1900\u20136700 ms), L.melanoleuca (40\u201363 ms) , L.pallida (627\u2013729 ms), L.petrops (44\u201357 ms), L.puhoatensis 6\u201314 ms, L.shangsiensis (64\u201369 ms), L.tadungensis (248\u2013353 ms) and L.yingjiangensis (28\u201342 ms).By call duration 117\u2013156 ms, L.liui, L.oshanensis, L.purpuraventra, L.bijie, L.suiyangensis, L.chishuiensis, and L.ventripunctata) of the genus occur in Guizhou Province, China , dorsal surface shagreened with small granules, and lacking enlarge tubercles or warts (vs. dorsum with round tubercles in the latter); differs from L.oshanensis by having narrow lateral fringes on toes (vs. lacking in the latter); differs from L.purpuraventra and L.suiyangensis by heels overlapping when thighs are positioned at right angles to the body (vs. just meeting in the latter); differs from L.purpuraventra by tibia-tarsal articulation reaches the middle eye when leg stretched forward (vs. only reaches the level between tympanum to eye in the latter).Seven species , heels overlapping when thighs are positioned at right angles to the body (vs. just meeting in the latter), having longer call interval , having lower dominant frequency of 4525 \u00b1 0.065 Hz vs. 4780.4 \u00b1 76.5 Hz in the latter, having significantly higher value of SVL in males, and having significantly higher value of TYD and TL to SVL in males. Leptobrachellajinshaensis sp. nov. differs from L.chishuiensis by webbing on toes absent (vs. webbing rudimentary in the latter), tibia-tarsal articulation reaches the middle of eye when leg stretched forward (vs. reaches the tympanum or the level between tympanum to eye in the latter), the lower dominant frequency of calls 4500\u20134688 Hz vs. 6064\u20136284 Hz in the latter, each call with two kinds of notes vs. only one kind of note in the latter, and having significantly higher value of HDW, SL, IOD, TYD, TEY and FL to SVL in males \u201d.The specific name L.bijie and L.chishuiensis. Although the relationships between the new species and other closely related species were not resolved, the new species appears to be phylogenetically closer to L.bijie and L.chishuiensis, corresponding to their high similarity on morphology. However, the new species appears to have lower dominant frequency on calling than the two closely related species. Moreover, they could be separated by morphometric analyses on contributions of some characters, for example, on PC1 of PCA, several characters of head, SVL and FL, which might be associated the calling behaviours, breeding behaviours, and jumping behaviours. We need future work to detect the function of the characters of these species to explore the ecological differences between them.Molecular phylogenetic analyses, detailed morphological comparisons, and advertisement call data all supported the new species distinctly separated from its congeners especially the superficially-morphological-similar species, Leptobrachella but did not included samples of Leptobrachellajinshaensis sp. nov. Similarly, this large phylogenetic framework likely included a few population samples in Guizhou Province, China. However, the phylogenetic framework indicated that Guizhou Province might be the biogeographical zone of transition for western-to-eastern or southwestern-to-northeastern clades obviously supply important supplemental materials for detecting detailed evolutionary and biogeographical models of the genus. Moreover, the findings of the new species also indicated a high degree of localised diversification and micro-endemism for the species in the genus Leptobrachella because in Guizhou Province, China, the five recent-described Leptobrachella species are just known only from their type localities or nearby areas. In addition, in recent years, large number of discoveries have been made from Guizhou, dramatically raising the number of frog species known from the region (The large-scale molecular phylogenetic analyses in n clades . The fine region . This fu"} +{"text": "Culex pipiens complex play a key role in the transmission and therefore epidemiology of a number of human and animal pathogens globally. These mosquitoes, and sympatric species of the genus Culex Linnaeus that are not within the Cx. pipiens complex, are often considered \u2018impossible\u2019 to distinguish by morphology in the adult female stage. In the United States, this is particularly true for Culex pipiens s.l. and Culex restuans Theobald, both of which are competent vectors of West Nile virus, but likely play different roles in the transmission cycle. Therefore, we undertook an in-depth morphological evaluation of matched larval exuviae and adult specimens that revealed five useful morphological characters that are informative to distinguish Cx. pipiens s.l. from Cx. restuans in the adult stage. Herein, we provide a comprehensive review of the literature on these species of interest, and four additional, morphologically similar, Culex species, and a proposed key to adult female specimens.Mosquitoes (Diptera: Culicidae) in the Culex pipiens Linnaeus is the namebearing taxon for the family Culicidae (Order Diptera) and is a member of one of the most taxonomically challenging complexes of species of mosquitoes. In the United States, the Culex pipiens complex is represented by Culex pipiens Linnaeus and Culex quinquefasciatus Say, as well as hybrid forms of those two . In particular, in Eastern and Midwestern states, members of the Cx. pipiens complex and Cx. restuans are key players in the transmission of WNV . Importantly, we also report that four other Culex species were poorly characterized in certain keys and other reference type literature, and specimens of these six species could be misidentified as one another if based only in said characters, so we included those extra four species in our analysis.Although it is possible to distinguish these species using a PCR diagnostic, morphological identification would facilitate rapid processing of field-collected mosquitoes. Therefore, we aimed to develop accurate morphological diagnostic criteria for these two Cx. pipiens s.l. and Cx. restuans adult females, and report five characters that may be useful in the differentiation of these two species. The utility of these characters for separating Cx. pipiens s.l. and Cx. restuans was validated using the PCR diagnostic for Cx. pipiens, Cx. restuans, and Culex salinarius Coquillett as described by Culex species, including both Cx. pipiens s.l. and Cx. restuans.We performed an in-depth analysis of distinct character states between Cx. restuans and Cx. pipiens s.l. from one another and other morphologically similar species are presented here for each of the published keys to mosquitoes of North America, i.e., The characters that are used in key couplets to separate adult female Cx. restuans from Cx. pipiens s.l. up until now has been the middorsocentral patches of pale scales on the scutum . Indeed this character separates Cx. pipiens from Cx. restuans according to The second most used character (and perhaps the one portrayed by keys as the most reliable choice) is the narrowing basal \u2018pale banding\u2019 towards the edges of the abdominal terga, which Ross used to separate Cx. erythrothorax Dyar, Cx. interrogator Dyar & Knab, Cx. chidesteri Dyar, Cx. salinarius Coquillett, and Cx. pipiens s.l. and Cx. restuans Theobald. In the analysis below key characters are presented that can be used to distinguish these species in the context of the body regions for which diagnostic characters have been reported.Morphological similarities similarly confound the identification of Cx. restuans from Cx. pipiens by the middorsocentral pale scaling on the scutum Cx. interrogator from Cx. restuans by the lack or usually presence of middorsocentral spots of pale scaling on the scutum, respectively. Means and Andreadis et al. also mentioned the existence of a patch of middorsocentral pale scales on the scutum of Cx. restuans as diagnostic for the species from the species that have narrow to nonexistent basal \u2018pale banding\u2019 . Means also separated Cx. salinarius from Cx. restuans + Cx. pipiens by the presence of the very narrow \u2018pale banding\u2019, often absent, adding that segments VII and VIII are mostly covered by pale yellow scales and uses the character of narrowing basal \u2018pale banding\u2019 of the tergites to separate Cx. pipiens from Cx. restuans the presence of short brown scales on the mid lobe of the scutellum of Cx. salinarius, in contrast to these scales long and pale in Cx. pipiens s.l. and Cx. restuans; 2) the sternites entirely covered by \u2018copper\u2019 scales in Cx. salinarius; 3) the \u2018dingy yellow to copper colored\u2019 scales forming the basal \u2018bands\u2019 of the tergites, these very narrow to absent on II and III, in contrast with the same character as yellow or \u2018cream\u2019 colored and appearing \u2018convex\u2019 for Cx. pipiens s.l. (narrowing towards edges), whereas those from Cx. restuans are white colored and appearing broad and connected with the basolateral patch. The authors noted that some character overlap exists with Cx. pipiens s.l. and Cx. restuans; 4) the \u2018dingy yellow to copper colored\u2019 scales covering tergites VII and VIII, presumably in contrast with the scaling pattern of tergites VII and VIII not different from other tergites in Cx. pipiens s.l. and Cx. restuans; 5) \u2018reddish-brown\u2019 coloring of the thoracic integument in Cx. restuans, in contrast with the \u2018tan to brown\u2019 coloring in Cx. pipiens s.l.; the scales of the scutum \u2018dark brown\u2019, short and not falcate in Cx. restuans, in contrast to \u2018light brown\u2019, long and falcate in Cx. pipiens s.l. The authors report a success rate of identification in using this combination of characters of 100% for Cx. pipiens, 100% of Cx. salinarius, and 80% for Cx. restuans, for which the remaining (20%) of misidentified specimens were Cx. pipiens , where the mosquito leg is placed in a tube with 50 \u00b5l of 25 mM NaOH + 0.2 mM EDTA at pH 12, which is heated to 95\u00b0C for 1 h then cooled down to 4\u00b0C and 50 \u00b5l of 40 mM EDTA at pH 5 is added.Genomic DNA was extracted from a single mosquito leg utilizing the protocol described by Johnston Cx. pipiens s.l. (PQ10) CCTATGTCCGCGTATACTA; forward primer for Cx. restuans (R6) CCAAACACCGGTACCCAA; forward primer for Cx. salinarius (S20) TGAGAATACATACCACTGCT. The PCR mixture for each tube consisted of 1 \u00b5l of extraction product, 1.5 \u00b5l of each primer at a concentration of 10 \u03bcM, 5 \u00b5l of GoTaq Flexi Buffer (5x), 2.5 \u00b5l of MgCl2, 0.5 \u00b5l of dNTPs, 0.125 \u00b5l of GoTaq DNA Polymerase, Promega, Madison, WI, in a total reaction volume of 25 \u00b5l. The thermocycler program was set to one cycle at 96\u00b0C for 4 min, 40 cycles at 96\u00b0C for 30 s, 51\u00b0C for 30 s, 72\u00b0C for 90 s, and one cycle at 72\u00b0C for 4 min. The PCR products were subject to electrophoresis in 2% agarose gel with ethidium bromide; a PCR product without DNA template was used as negative control. Culex pipiens s.l., Cx. restuans, and Cx. salinarius were identified according to the amplicon size as visualized on the gel, as described by In accordance with previous literature, the primers used for molecular identification were designed by Cx. pipiens s.l. and Cx. restuans) used for analysis of morphological characters were reared from eggs collected in standing water inside tires in Monona , DeForest [21.VI.2017], and Janesville [15.VI.2017], Wisconsin. Larvae were reared individually in tap water in plastic cups and fed dry yeast. The fourth-instar exuviae were collected and slide mounted in Canada Balsam for confirmation of taxonomic identity, whereas the adults were point mounted and stored dry.The mosquitoes (Cx. pipiens s.l. and Cx. restuans were determined utilizing these specimens (n = 14). The same specimens were used to confirm the mosquitoes of our region were correctly identified by the primers from Characters of interest for identification of n = 99). For each specimen, the taxonomic identity was determined using the morphological characters proposed here, and then a leg sample was removed and encoded to be subjected to a blinded molecular identification utilizing the molecular methods described. These additional mosquitoes were collected from All Saints Cemetery, Des Plaines, IL. and from Blaine , Anoka , Waconia , Mendota Heights , Minnetrista , Lauderdale , St. Paul , Shakopee , and Cedar Lake , Minnesota.Additional adult female mosquitoes from field collections were used to confirm the utility of the characters found by the previously discussed morphological analysis , distributed from occiput to vertex, were all dark colored in Cx. restuans were more numerous in Cx. restuans than in Cx. pipiens s.l. on the thorax, as viewed laterally, was useful for separation of Cx. pipiens s.l. (Cx. pipiens s.l. (Cx. restuans (The coloration of the setae of the postpronotum (PpS) and of the mid lobe of the scutellum (MSS) proved to be useful in our samples as well. For this character, some or all of the setae of the postpronotum were golden/pale in ens s.l. , as wellens s.l. ; in contrestuans and F. TCx. pipiens s.l. may be of some use in the separation of those species, as they appear to be lighter colored and thinner in appearance in ens s.l. and veryrestuans . FurtherCx. pipiens s.l. and 26 adult female specimens to Cx. restuans, from material collected from Des Plaines, Illinois, U.S.A. , and from Blaine, Anoka, Waconia, Mendota Heights, Minnetrista, Lauderdale, St. Paul, Shakopee, and Cedar Lake, Minnesota in 2017 and 2018. Each specimen was morphologically identified using the combination of characters described above, then subjected to PCR based identification using the method described in To confirm the molecular identification of laboratory reared adults, for which each morphological identification was confirmed with the larval exuvia, DNA was extracted from a single leg and subjected to PCR for the ITS segment using methods and primers from Cx. salinarius, as compared to long and pale scales in Cx. pipiens s.l. and Cx. restuans to distinguish these species and confirmed the presence of this character state, and PCR for the ITS sequence yielded a product with the correct band size using the primers and methods described by Cx. salinarius, the character described by per se, so we refer to it as \u2018copper-colored\u2019.In addition to these findings, we tested and found support for the utility of the presence of short brown scales on the mid lobe of the scutellum on Culex species if this is the character on which the observer is focused.In the process of assessing these specimens and character states, we also had the opportunity to assess the characters previously used to distinguish these species using existing dichotomous keys. Our experience with characters related to the coloration and shape of the abdominal tergite basal \u2018pale bands\u2019 corroborated that of Apperson et al. and Harrington and Poulson, who noted that the character state overlaps in specimens and is of little use for separation of said species , 2008. BCulex erythrothorax . The same can be said of the character of scutal scaling. We did find that the scutal scales are dark brown and short in Cx. restuans, as compared to bright yellow and rather long in Cx. pipiens s.l.; however, the shape of the scales is not well described as \u2018not falcate\u2019 in Cx. restuans, as reported by Cx. restuans in our sample seemed to be falcate, but not dorso-ventrally expanded by a significant amount, which gives them a more \u2018hair-like\u2019 appearance at a glance, rather than the more archetypal falcate scales present in Cx. pipiens s.l. This character may furthermore be misinterpreted as the \u2018hair-like\u2019 scales of Cx. erythrothorax as presented in the keys of Carpenter and LaCasse (1955/1974) and Darsie Jr and Ward , resulting in a misidentification. Additionally, Cx. salinarius observed herein from Wisconsin also presented the character of short brown scutal scales, with lack of significant dorsovental expansion, giving a more \u2018hair-like\u2019 appearance than the ones of Cx. pipiens s.l.Furthermore, we did not find that thoracic integument coloring was useful for identification of these mosquitoes from this region. The use of this character is not consistent in the literature, with most modern Nearctic keys attributing the \u2018reddish brown\u2019 character as exclusive to Cx. pipiens s.l. and Cx. restuans are morphologically differentiable, but existing keys do not sufficiently delineate the morphological differences between these two species to provide a reliable identification. The combination of characters described herein may be of use to ascertain the correct identification of a few Culex species that currently have equivocal characters in available keys. Should the user identify Cx. erythrothorax, Cx. interrogator, Cx. chidesteri, Cx. salinarius, Cx. pipiens s.l., or Cx. restuans using existing keys, the characters below should provide a degree of certainty to the identification. The following key was derived from characters present in the literature and those presented in this paper. The key should be taken as provisional until these characters have been thoroughly vetted for specimens of these species from different regions of the Nearctic or, preferably, the American continent as a whole. Additional research is needed to further increase our knowledge of the morphological traits of all these species, and also to improve and update reference material (both keys and descriptions) for the Nearctic mosquito fauna.In summary, Culex (Culex) species that have been mischaracterized in reference material or have not been adequately separated in previous keys. More specifically, we recommend the consultation of the following key if the reader arrives at the identification of Cx. erythrothorax, Cx. interrogator, Cx. chidesteri, Cx. salinarius, Cx. pipiens s.l., or Cx. restuans by utilizing current keys to Nearctic Culex species. We believe this provides a more accurate identification, at least within Midwestern states in the United States, with the limit of its usage confined to the Nearctic region, due to the likely variation in the character states of Neotropical Cx. restuans in relation to the Nearctic.The purpose of this key is to provide a way to confirm the identities of certain 1. Abdominal tergites VIII and most of VII pale scaled, other tergites bearing narrow basal pale bands, sometimes indistinct; abdominal sternites covered by pale scaling only; base of mid lobe of scutellum with short \u2018copper colored\u2019 scales or with long pale scales .................................................................... 2Abdominal tergites with basal pale bands, usually rather broad, rarely very narrow to indistinct; abdominal sternites mostly covered by pale scaling, usually with dark scales intermixed; base of mid lobe of scutellum with long pale scales .................................................................................................. 3Cx. erythrothorax2(1). base of mid lobe of scutellum with long pale scales .............................................................................. Cx. salinariusbase of mid lobe of scutellum with short \u201ccopper colored\u201d scales; tergites usually with a few pale scales scattered at apex ........................................................................... Cx. chidesteri3(1). Postspiracular patch of scales usually present; very narrow pale rings at joint of tasomeres usually present; erect scales of dorsum of head dark ...................................................................................................................... Postspiracular patch of scales absent; joints of tarsomeres usually without pale markings; erect scales of dorsum of head dark or pale ones medially .................................................... 42 + 3 about one third of the length of wing cell R2, erect scales of dorsum of head dark ......... Cx. interrogator4(3). Wing vein R2 + 3 about one sixth or about one fourth the length of wing cell R2, if one fourth, then erect scales of dorsum of head pale medially ............................................................ 5Wing vein RCx. restuans5(4). Middorsocentral patches of pale scaling present or absent; erect scales of dorsum of head dark ; upper pCx. pipiens s.l.Middorsocentral patches of pale scaling absent; erect scales of dorsum of head pale medially, others dark ; upper p"} +{"text": "Scientific Reports 10.1038/s41598-020-70839-9, published online 21 August 2020Correction to: The original version of the Article contained errors in the author names Maryam Ghaeidamini Harouni and Somayeh Rahimi Babasheikhali which were incorrectly given as Maryam Harouni Ghaeidamini and Somayeh Babasheikhali Rahimi.The Author Contributions section now reads:\u201cM.G.H. and S.R.B conceived the ideas and performed the experiments. M.G.H. and E.S.G. wrote the article. A.S. and E.S.G. did and wrote in silico studies. S.R. conceived the ideas, designed the study, wrote and reviewed the article.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Scientific Reports 10.1038/s41598-018-23109-8, published online 21 March 2018Correction to: The original version of this Article contained a typographical error in the spelling of the author Nassima Chouaki Benmansour, which was incorrectly given as Nassima Chouaki-Benmansour. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:\u201cY.H., N.C.B., K.R., A.-M.S., M.-C.P., A.S., E.B., A.W., G.C. designed the study, performed the experiments and analyzed the results. G.C., M.F., S.B., C.B., A.F., S.M. assisted with realization and interpretation of the experiments, and provided several reagents. B.P., D.M., S.B., Y.H. and H.-T.H. supervised and directed the research. Y.H., N.C.B. and H.-T.H. wrote the manuscript. All authors discussed the results and commented on the manuscript.\u201d"} +{"text": "Nature Communications 10.1038/ncomms12560, published online 30 August 2016.Correction to: The original version of this article included Seyed Reza Mahmoudi, who was\u00a0from \u201cDepartment of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts avenue, Cambridge, 02139, Massachusetts, USA\u201d,\u00a0as the second author in the author list. Subsequently this person stated that his contribution to the work was not sufficient to be included as an author. Consequently, this name has been removed from the author list. In addition, the sentence \u201cM.D., S.R.D, N.H. and K.K.V. conceived the project\u201d in the Author Contributions section has been corrected to \u201cM.D., N.H. and K.K.V. conceived the project\u201d. This has been corrected in both the PDF and HTML versions of the article."} +{"text": "Scientific Reports 10.1038/s41598-018-29602-4, published online 07 August 2018Correction to: In this Article, the authors neglected to include some potential conflicts of interest.The Competing Interests section should read:\u201cJ. L. is a founder of Glycan Therapeutics. D.F.T., Y.X., D.K., C.N., T.F., H.Q., L.W., K.W.M., R.J.W. declare no competing interests. J.D.E. is a co-founder of TEGA Therapeutics. J.D.E. and The Regents of the University of California have licensed a University invention to and have an equity interest in TEGA Therapeutics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.\u201d"} +{"text": "Trans. R. Soc. Trop. Med. Hyg. 97, 567\u2013569. doi: 10.1016/S0035-9203(03)80031-7.\u201d It should be \u201cKato, T. (2012). Development of the coping flexibility scale: evidence for the coping flexibility hypothesis. J. Couns. Psychol. 59, 262\u2013273. doi: 10.1037/a0027770.\u201dIn the original article, the reference for \u201cEl-On et al., 2003\u201d was incorrectly written as \u201cEl-On, J., Ben-Noun, L., Galitza, Z., and Ohana, N. (2003). Case report: clinical and serological evaluation of echinococcosis of the spine. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-020-64502-6, published online 04 May 2020Correction to: The Acknowledgements section in this Article is incomplete.\u201cWe sincerely thank J.Thevenot (UMS Patrinat), O. Lorvelec , B. Guillemot , H. Magnin and G. Van Laere , J. Chalifour , B. Angin (Ardops Environnement), A. Lenoble , M. Rutherford , and F. Catzeflis for sharing occurrence data. We thank the curators of the museums for providing access to specimens and data (see Table S1).\u201dShould read:\"We sincerely thank J.Thevenot (UMS Patrinat), O. Lorvelec , B. Guillemot , H. Magnin and G. Van Laere , J. Chalifour , B. Angin (Ardops Environnement), A. Lenoble , M. Rutherford , and F. Catzeflis for sharing occurrence data. We thank the curators of the museums for providing access to specimens and data (see Table S1). This project received funding from the region Ile de France (ARDoC) and from the Investissement d\u2019Avenir Project Labex BCDiv (ANR-10-LABX-0003).\u201d"} +{"text": "Lepus oiostolus is widely inhabited in the Qinghai-Tibet Plateau. So far, little mitochondrial genome information of this genus has been described. To grasp a better comprehension on the molecular basis of L. oiostolus, we obtained the complete mitochondrial DNA genome sequences of this species. The mitogenome was 17,320\u2009bp in length, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 noncoding regions. The complete mitochondrial genome of L. oiostolus would be of great utility in the phylogenetic analysis of the Lagomorpha and also provide meritorious insights into the deeper problems of the phylogenic analysis. Lepus oiostolus is an endemic species in the Qinghai-Tibet Plateau, also known as gray-tailed hare. It belongs to the genus Lepus . The genome DNA was extracted from the muscle tissue, using a modified method from the standard phenol/chloroform extraction process . It is a double-stranded closed loop structure composed of 13 protein-coding genes (PCGs), 2 rRNAs, 22 tRNAs and a D-Loop region. The overall base composition of the whole mitochondrial genome is 32% A, 29.4% T, 25.6% C, and 13.1% G, exhibiting obvious AT bias (61.4%).The mitochondrial genome of L. oiostolus with 15 species of Lepus from GenBank were resolved by means of Neighbor-joining (NJ) and an Oryctolagus cuniculus as outgroup. The NJ tree was built using MEGA 7 (Kumar et\u00a0al. L. oiostolus, L. tolai, L. capensis, L. corsicanus, L. timidus, L. othus, L. arcticus, L. townsendii, L. tibetanus subsp. pamirensis, and L. sinensis have a closer relationship compared with other species studied (L. oiostolus for the future research.Phylogenetic relationships of studied . Hares m studied . This st"} +{"text": "This article presents a general overview of the prevalence, genetic diversity and detection methods ofpicobirnaviruses (PBVs), which are small, non-enveloped icosahedral viruses with a segmented double-strandedRNA genome consisting of two segments taxonomically related to the genus Picobirnavirus of the family Picobirnaviridae.This review of scientific papers published in 1988\u20132019 provides data on the PBV distribution in the natureand a broad host range. PBV infection is characterized as opportunistic, the lack of understanding of the etiologicalrole of PBVs in diarrhea is emphasized, since these viruses are detected both in symptomatic and asymptomaticcases. The concept of PBV infection as a chronic disease caused by a long-lasting persistence of the virus in the hostis considered. Such factors as stress syndrome, physiological conditions, immune status and host age at the timeof primary PBV infection influence the virus detection rate in humans and animals. The possible zoonotic nature ofhuman PBV infection is noted due to the capacity for interspecies PBV transmission acquired during evolution asa result of the reassortment of the genome segments of different viruses infecting the same host. Data providingevidence that PBVs belong to eukaryotes and a challenging hypothesis stating that PBVs are bacterial viruses arepresented. The need to intensify work on PBV detection because of their wide distribution, despite the complexitydue to the lack of the cultivation system, is emphasized. Two strategies of RT-PCR as main PBV detection methodsare considered. The genomes of individual representatives of the genus isolated from different hosts are characterized.Emphasis is placed on the feasibility of developing primers with broader specificity for expanding the rangeof identifiable representatives of the genus PBV due to a huge variety of their genotypes. The importance of effectivemonitoring of PBV prevalence for studying the zoonotic and anthroponotic potential using metagenomicanalysis is highlighted, and so is the possibility of using PBV as a marker for environmental monitoring. In 1988 in Brazil when human fecal samples collected duringacute gastroenteritis outbreaks were subjected for detectionof segmented rotavirus genomes by polyacrylamide gelelectrophoresis (PAGE), two band profiles were revealed. Similar profiles were found whenexamining intestinal contents of rats .These segments were double stranded RNA (dsRNA). Theirlength was estimated by electrophoretic mobility at about2.6 and 1.5 kbp for the slow- and fast-migrating segments,respectively. This RNA was cosedimented in the caesiumchloride gradient at a density of 1.39\u20131.40 g/ml with uniformparticles ~35 nm in diameter with an indistinct surfacestructure, detected by electron microscopic examination ofsamples. The authors proposed the name \u201cpicobirnaviruses\u201d, bi (\u2018two\u2019), and rna (\u2018RNA\u2019)) for new,previously undescribed small viruses with a bisegmentedRNA genome, in contrast to the known larger birnavirusesthat infect birds, fish, insects, and mollusks.Follow-up studies showed a widespread prevalence ofpicobirnaviruses (PBVs) that were found in the feces ofterrestrial and marine mammals, reptiles, birds , in the respiratory tract of pigs and humans , in fish, invertebrates, fungi ,and, according to recent data, in bacteria . The chronology of PBV detection in humansand animals according to data from 1988 to 2018, inclusive,is presented in the Table.https://viralzone.expasy.org). This new viral family is composed of only oneviral genus, Picobirnavirus, uniting the viruses of five geneticallyvariable clusters (genogroups) Picobirnaviruses (family Picobirnaviridae) is a family ofnon-enveloped small spherical viruses, according to Baltimore\u2019sclassification, belonging to the class III of viruseswith a double-stranded RNA genome in 2008 . Picobirnavirusesfrom other hosts have not yet been approved astype species and are considered unclassified . In addition, it is not completely clear whether eukaryotes or bacteria are the natural hostsof PBVs . Information aboutthe taxonomy of Picobirnaviridae is available in the ICTVreport summary by reference at the link www.ictv.global/report/picobirnaviridae. Taxonomically, the closest relativesof PBVs are viruses of the family Partitiviridae, thathave a similar capsid structure and genome organization. Natural hosts of partitiviruses arefungi and plants .Morphologically PBV virions are small non-envelopedparticles 35\u201340 nm in diameter with indistinct surfacestructure . A capsid has acubic type of symmetry, has a 30-sided organization, and consists of 60 asymmetricsubunits that are homodimers . These subunits form60 protrusions on the surface of the capsid. Since eachof the subunits is a dimer, in total, the capsid consists of120 protein molecules, which makes it possible to attributePBVs to structures with a triangulation number \u201cT = 2\u201dwhen characterizing the virion symmetry. In the capsidthere are channels connecting the internal cavity with thevirion surface .Significantly different in capsid architecture from highereukaryotic viruses with dsRNA (Reoviridae), PBVs aresimilar to dsRNA viruses of the family Partitiviridae. However, according to recent data,in contrast to partitiviruses, PBVs can infect prokaryoticcells in addition to fungal host cells .PBV genome consists of two dsRNA segments whosesizes differ in viruses isolated from different animal species.In polyacrylamide gel electrophoresis (PAGE) these segmentsdiverge relative to each other at a certain distance. Inthis case, two types of electrophoregrams are formed: witha larger (segments higher) genome profile andwith a shorter genome profile .The larger segment 1 of the PBV genome can consist oftwo or three open reading frames (ORF). It should be notedthat in most studies, the segment 1 of the PBV genome isschematically represented as two ORFs, for example, inthe PBV genome schemes of human ,pig , bull , sealion , fox , turkey , horse , gorilla, marmot . Ina number of other works, the segment 1 consists of threeORFs, for example, in the genome schemes of rabbit, roedeer and chicken in studies of Green et al. (1999), Kuharet al. (2017) and Boros et al. (2018), respectively.In schemes where the segment 1 consists of three ORFs,the smallest ORF1 encodes a polypeptide comprising only afew tens of amino acids. For example, in the scheme of thehuman PBV genome (strain Hy005102) presented by Kinget al. (2012), ORF1, preceding two larger frames ORF2and ORF3 encoding peptides of 224 and 552 amino acids,consists of only 39 codons . In the PBV genomeschemes of rabbit, roe deer and chicken in the studies ofGreen et al. (1999), Kuhar et al. (2017) and Boros et al.(2018) ORF1 is slightly larger and comprises 55, 63 and188 codons, respectively. The functionality of ORF1 isunclear, and therefore its presence is not always mentionedby other researchers .ORF2 in schemes with the segment 1, consisting of threeORFs, encodes the so-called hydrophilic peptide containingconserved repeating sequences, which is one of the mainfeatures of the PBV genome . There isan assumption that two frame shifts occur during translationto generate one long protein .The third, the largest reading frame (ORF3) in the PBVsegment 1 encodes a virus capsid protein of 552\u2013591 aminoacids. Frames may overlap. In the scheme of King et al.(2012), the three ORFs overlap at eight (ORF1\u2013ORF2junction) and one (ORF2\u2013ORF3 junction) nucleotides.The shorter segment 2 of the PBV genome contains oneORF encoding the enzyme RNA-dependent RNA polymerase(RdRp) . Depending on differences inRdRp gene specificity in the segment 2 of the PBV genome,PBVs are divided into genogroups .In addition to the \u201ctypical\u201d PBVs described above,\u201catypical\u201d PBVs were detected using PAGE, first in thefeces of calves , and laterin the human feces . \u201cAtypical\u201d PBVs have a smaller genomethan \u201ctypical\u201d ones (RNA segment sizes range from 1.75to 1.79 kbp and from 1.37 to 1.55 kbp), and differ in thelocation of genes encoding functional proteins . If in \u201ctypical\u201d PBVs,the segment 2 encodes the viral RNA polymerase, and thesegment 1 encodes a capsid protein, then in \u201catypical\u201d onesit is the opposite.The PBV genome is usually segmented . However, several nonsegmentedPBV genomes belonging to different geneticclusters have recently been described, particularly PBVgenomes of horses , of Himalayan marmots, fish and invertebrates . It was found that there is an evolutionary relationshipbetween PBVs with a segmented and non-segmentedgenome, which is due to the possibility of transition fromone form to another. It turned out that the PBV genomeof marmots can be both segmented and non-segmented.A non-segmented genome contains three ORFs \u2013 ORF1,ORF2, ORF3 encoding a hydrophilic protein, a capsidprotein, and RdRp, respectively .Sequencing studies of PBVs have shown that PVBs areextremely variable . PBV genome variability is explained by characteristicgenetic variability, caused not so much by a change inthe primary structure as a result of mutations, but by thegenome segment reassortment .https://www.ncbi.nlm.nih.gov/nuccore), as of 17.07.2014 it was noted that 83.11 % of the sequencesbelong to the PBV genogroup I (GI), and only 2.52 % \u2013 tothe genogroup II (GII), which corresponds to the prevalenceof representatives of these genogroups in nature.Until 2014, researchers identified two main PBV genogroupsbased on the study of short incomplete RdRp genesequences . When analyzing the PBVsequences presented in the database GenBank and in the environment. The new human PBV showed lowsimilarity (19.4\u201326.1 %) in the sequence of amino acids inthe RdRp gene product with the human PBV genogroupsI and II, which allowed them to be assigned to the genogroupIII (PBV GIII/Homo sapiens/VS6600008/2008/NL/KJ206569 in GenBank). In 2015 picobirnaviruses wereidentified in horses, which formed separate clusters andwere assigned to two genogroups GIV and GV during phylogenetic analysis of 450 aa RdRp protein sequence.Thus, picobirnaviruses are currently classified into fivegenogroups GI\u2013GV based on RdRp sequences. At thesame time, the intra-genogroup amino acid identities rangefrom 44.8 to 97.1 %, whilst the inter-genogroup aminoacid identities range from 21.6 to 30.8 % .In humans, four PBV genogroups \u2013 GI, GII, GIII and GV were identified.All five PBV genogroups were identified in the marmot. Genogroup GIII PBVs were found indiatomsand invertebrates .According to the currently accepted nomenclature ofpicobirnaviruses proposed by Fregolente et al. (2009),the name of the strain begins with the genogroup name(GI\u2013GV), followed by the abbreviation PBV, the commonname of the host species, the three-letter country code, thename of the strain and the year of isolation, separated bya slash. Using this nomenclature, PBV strains detected inhumans and turkeys received the following designations \u2013GI/PBV/human/BRA/PBV_RVH275/2013 (human PBV)\u0438 GI/PBV/turkey/USA/MN-1/2011 (turkey PBV).In spite of the fact that PBVs are often detected from humansand animals with diarrhea separately and co-infectionwith other pathogens , the roleof PBVs as causative agents of intestinal disorders hasnot been established, since these viruses are detected inasymptomatic cases . For example, Verma etal. (2015) showed that the excretion of PBVs in turkeyswas not associated with the symptoms of diarrhea. Of the80 fecal samples from poultry with diarrhea and 40 withoutdiarrhea, 39 (48.8 %) and 23 (57.5 %) were positive forPBVs, respectively.It is not shown, that PBVs might have etiological relationwith diarrhea in humans and animals infected with otherpathogens that cause gastroenteritis. The adaption of thevirus to grow in the cell culture and experiments on gnotobioticanimals will be essential to establish the etiologicrole of PBVs .Since the end of the 90s of the last century, PBVs havebeen identified as opportunists for their ability to provokediarrhea in animals infected with the primary pathogen orhumans with weakened immunity and later to manifestthemselves as a chronic disease with or without signs ofdiarrhea . There is a concept about the opportunistic nature of PBV infection, whichis presented in the review published by Ganesh et al. (2014)and other reports based on the results of examination ofhealthy animals for the presence of PBVs . According to this concept, the chronic nature of PBV infectionis explained by the long-term persistence of the virus inthe host body . The persistent natureof PBV infection is manifested by periods of silence, inwhich the virus is not detected even using highly sensitivemethods, intermingled with periods of viral activity. In thiscase, adult animals infected with PBVs could be asymptomaticPBV carriers or may be persistently infected andserve as reservoirs of the infection. In particular, researchresults obtained by Carruyo et al. (2008) shown that PBVscan infect piglets 7 to 56 days of age .The virus excretion level by virus carriers is affected bya number of factors such as stress syndrome, physiologicalstatus, age of the primary infected individual, immunestatus of the hosts, and environmental conditions (biotic andabiotic factors). These factors contribute to an increase inthe viral load. When taking samples based on these factors,the detection of PBVs by the PAGE was observed with ahigher frequency.The dependence of the PBV excretion level on thestress caused by keeping animals captive was observedin African green monkeys from the Caribbean Islands in2014\u20132015 . 270 fecal sampleswere collected from wild and captive monkeys subjected to PAGE for PBVs.16 samples (14.5 %) from captive monkeys kept understressful conditions were indicative for PBVs. None of thefecal samples from wild monkeys was tested positive forPBVs .The dependence of the PBV excretion level on the physiologicalstatus of pigs, in particular during the reproductionperiod, was studied by researchers in Argentina. Observations showed that PBVspersisted in the host as a permanent infection, with periodsof low and high PBV excretion intermingled with periodsof silence. Low PBV excretion levels were detected byreverse transcription followed by polymerase chain reaction(RT-PCR) throughout the study period. In case of sharpincrease in the PBV excretion level in pigs, observed duringfarrowing and lactation periods, the virus was detectednot only by OTP-PCR, but also by PAGE. PBV detectionrate was highest in the group of sows sampled within thelactogenic period (38.02 % of samples collected from71 sows), followed by pregnant sows at the final stage ofgestation (15.09 % of samples collected from 53 pregnantsows) .The dependence of the PBV excretion level on the age ofthe animal is shown. From 289 fecal samples of individualcalves between 5 and 60 days of age analyzed by PAGE thePBVs were detected in 24 (8.3 %) In the study , a high PBV excretionlevel in pigs was observed in young animals 2\u20135 monthsof age (18.42 %), while no excretion was observed in adultmale pigs. Studies on turkeys also revealed a change in thefrequency of PBV excretion . 39 of 80(48.8 %) fecal samples from turkeys were PBV positive. The maximum number of samples was positive in turkeysat 2 weeks of age (20 of 20) followed by 3 weeks of age (15of 20). A sharp decrease in the number of positive samples(2/20 were positive at 8 weeks of age) indicated a decisiveinfluence of age on this process.The PBV excretion level is also affected by the host\u2019simmune status. It was found that in people with weakenedimmunity, PBVs are detected more often. For example,Giordano et al. (1998) when investigating 197 stool samplescollected from HIV-infected and noninfected patients withand without diarrhea for the presence of PBVs by PAGEdetected PBVs in 8.8 % of 57 HIV-infected patients withdiarrhea, but detected it in neither those without diarrheanor in the group of subjects uninfected with HIV.Further research by these authors reinforced their view ofthe relationship between PBV excretion levels and diarrhoeain HIV-infected individuals. In a study of 244 stoolsamples from HIV-infected and uninfected patients withand without diarrhea, PBVs were detected in 14.63 % of82 HIV-infected patients with diarrhea and it was detectedneither in those without diarrhea nor in the group of subjectsuninfected with HIV . At a certainPBV excretion level, PBVs are detected in HIV-infectedpatients without signs of diarrhea, for example, Gonz\u00e1lezet al. (1998) detected PBVs in 2.3 % of 125 HIV-infectedpatients without diarrhea .The PBV excretion level may be influenced by bioticenvironmental factors such as primary pathogens. In somestudies, for example, PBVs are most often isolated as coinfectedagents with a number of diarrheal causes, such asrotaviruses , or noroviruses . These studies indicated that PBVs might haveplayed synergistic effect in association with the primaryenteric causes .Climate factors such as sunlight , temperature, and humidity also affect the viral activity. These factors that affect thePBV excretion level should be taken into account whenidentifying them.Most human viral diseases are of zoonotic origin. Thezoonotic character of the PBV infection is indicated bythe detection of genetically related PBVs in humans andanimals. In particular, from pigs in Hungary, Venezuela andArgentina genogroup I PBVs were detected which, whensequencing the genome, showed genetic similarity to thehuman genogroup I PBVs . There have been reportsof PBV strains found in children in Calcutta that are geneticallyrelated to porcine PBV strains . Equine PBV strains isolated from the faeces offoals in Calcutta (India) showed a genetic relationship withhuman strains from the same city .The detection of genetically similar PBVs in humans andfoxes , in humans and bats has been reported. For example, the report notedthat the cause of zoonotic transmission of PBVs to humansfrom bats in Cameroon is the hunting and eating of bats.Zoonotic PBV transmission is one of the variants ofinterspecies transmission. The capacity for interspeciestransmission was acquired by PBVs in the course of evolutiondue to the reassortment of segments of their genomewhile simultaneously infecting a single cell by PBVs ofdifferent species . The geneticlability caused by reassortment could lead in the courseof evolution either to genetic convergence of PBV strainsbelonging to different hosts or, conversely, to genetic divergence\u2013 genetic distance of PBV belonging to hosts ofthe same species .The capacity for interspecies PBV transmission is confirmedboth in the cases of zoonotic infections, and in casesof infection of animals with human PBVs, for example,young pigs or horses . The genomes of some porcine PBV strains werefound to be identical to those of human genogroup I PBVs. In 2011, genetically similar PBVswere found in the respiratory tracts of pigs and humans.Genetic divergence of related PBV strains was demonstratedby Zhang B. et al. (2014). Thus, three of four porcinePBVs identified in the study were genetically closer tohuman PBVs than to previously revealed porcine PBVs.It is possible to transfer PBV strains from one host toanother through fecal-contaminated raw sewage . In an environmental study Symonds et al.(2009) showed that picobirnaviruses are potentially usefulviral indicators of fecal pollution of naturally impoundedbodies since they were found in 100 % of raw sewagesamples and 33 % of final effluent samples.PBVs commonly found in animal fecal samples are currentlythought to be animal viruses, but no animal modelor cell culture for PBV propagation has yet been found.Recently, some Indian scientists hypothesized that PBVsare prokaryotic RNA viruses .The hypothesis is based on the fact, that like prokaryoticviruses with the RNA-genome, in the PBV genome, thereare conserved ribosomal binding site (RBS) sequencescalled Shine\u2013Dalgarno sequences upstream of the threepresumed ORFs of the segment 1 and a single presumedORF of the segment 2. Such sites are 6-mers (AGGAGG)preceding codons that initiate the translation of the viralgenome sequences. In bacterial viruses, these 6-mers areribosomal binding sites and serve to enhance the translationefficiency of viral proteins. For example, such sitesare present in the genome of some bacteriophages of thefamily Cystoviridae with a segmented dsRNA genome.Findings obtained by Adriaenssens et al. (2018) supportthe hypothesis that PBVs are bacteriophages. The authors demonstrated a high incidence of 6-mer motif AGGAGGin the PBV genome. In contrast, the different families ofeukaryotic viruses analyzed in that study only showeda low incidence of SD-sequences, which were mostly4-mers . Findings supporting thebacteriophage-nature of PBVs were also obtained by Boroset al. (2018), who revealed in the chicken PBV genomethe presence of conserved prokaryotic Shine\u2013Dalgarnolike(SD-like) sequences upstream of the three presumedORFs of the segment 1 and a single presumed ORF of thesegment 2.If we assume that PBVs are prokaryotic viruses, we canexplain their widespread prevalence and a broad host range.Bacteriophages are widely distributed in nature. They arefound in water, soil, food products, various excretions ofhumans and animals, that is, where bacteria are found.The identification of PBV strains with genetically relatedgenome sequences in different animal species canbe explained by assuming that PBVs might actually infectbacteria that populate the enteric tract of vertebrates andinvertebrates. At the same time, the authors of the phagehypothesis believe that PBVsreplicate in bacteria of a certain type, in the genome ofwhich there is a prokaryotic SD-sequence in most genes(more than 10 %). Such bacteria are Firmicutes in thegenome of which there are more than 80 % of genes withprokaryotic SD-sequence .The authors point out, that, even viral families thatinclude species whose genomes are enriched for SDsequences,are exclusively prokaryotic viral families. Theacquisition of immunity against PBVs by infected animalsalso does not contradict the phage hypothesis, since it isestablished that immune responses can be raised againstbacterial viruses . It is possible that PBVs cause an immune responseto infection not of human cells, but of the bacterial cellsthat make up its microbiome, which again does not excludethe possibility that PBV are prokaryotic viruses.The possession of a capsid protein with perforation activity,which means the ability to translocate through thecell membrane , as proof that itcan infect animal cells, also does not contradict the phagehypothesis, since it is known that representatives of thebacterial RNA-virus family also have the ability to exitthe cell . The process of interaction ofhuman and animal PBVs with the host cell is similar to theprocess of interaction of a virulent phage with a bacterium,which proceeds in several stages \u2013 penetration into thebacterial cell, autonomous reproduction in it and lysis ofthe bacterium. Consequently, the perforation of liposomesby PBVs does not exclude that they may be prokaryoticRNA-viruses.Summing up the arguments in favor of the phage hypothesis,we can conclude that, perhaps, PBVs belong to a newfamily of RNA-viruses that infect a certain type of bacteriawith a genome with a high content of SD-sequences (morethan 80 %). These bacteria populate the intestinal tract of animals and humans and they can be bacteria Firmicutes,containing most genes with SD-sequences.These arguments strongly suggest that PBVs can actuallyinfect prokaryotes, not eukaryotes. And if PBVs actuallyinfect bacteria, then it is necessary to change the approachto their study \u2013 to direct efforts towards finding a host fortheir replication among prokaryotic cells, rather than eukaryoticones. Separation prokaryotic and eukaryotic virusfamilies by the frequency of the presence of SD-sequencesin the genome allows identifying new prokaryotic virusfamilies.Thus, the final proof of the phage nature of PBVs requiresthe selection of host cells for its replication. In alllikelihood, until successful cultivation of PBVs in specificbacterial cultures is achieved, the phage nature of PBVsremains hypothetical. Given the fact that gut microbiomeconsists of several hundreds of mostly uncultivable bacteriathe identification of true bacterial or archeal host(s) of PBVs(if any) will be challenging .Before the use of nucleic acid amplification methods, thedetection rate of PBVs remained extremely low, becauseof low sensitivity of the method of genomic RNA PAGE. In addition, PBVs are very labileagents. It is shown that samples tested PBV positive byPAGE, become negative after several freezing\u2013thawingprocedures .The low frequency of detection of PBVs by PAGE isevidenced by the work of Argentine virologists . These authors collected 2224 stool samples fromchildren with diarrhea over a 25-year period from January1977 to December 2002. Only two samples (0.09 %)were tested PBV positive by PAGE. Similar results wereobtained in our studies on the detection of rotaviruses byPAGE, in stool samples from children under 14 years ofage with acute intestinal infection, who were admitted toinfectious hospitals in the city of Nizhny Novgorod, NizhnyNovgorod region. For the period 1994\u20132001 PBVs werefound in only 3 of 4535 samples tested . Subsequently, from July 2006 to January 2010,PBVs were detected in 0.08 % of 3645 stool samples fromchildren with gastroenteritis .The use of PAGE limited the frequency of PBV detection,since at the low viral load virus excretion was undetectablein most clinical samples . A low frequency of PBV detectionby PAGE was reported by Cascio et al. (1996), Pereira et al.(1993) and Ludert, Liprandi (1993), in a study of sporadicgastroenteritis cases in children in Italy (0.43 %), Brazil(0.5 %) and Venezuela (0.5 %), respectively. However,in outbreaks of gastroenteritis, when the virus excretionlevel was high, the virus was detected by PAGE with asignificantly higher frequency. For example, Pereira et al.(1988a) reported a frequency of human PBV detection inoutbreaks of gastroenteritis in Brazil up to 20 %.The introduction of RT-PCR amplification and sequencingtechnologies has contributed to an increase in the PBVdetection rate in various wildlife objects. For example, a total60 % (87/144) of the fecal samples from newborn pigletstested were found to be PBV positive by RT-PCR (versus27 % by PAGE) . The informationpresented in the paper on the prevalence of porcine PBVsin Argentina also demonstrates thesignificantly greater capabilities of the RT-PCR methodcompared to PAGE. If the PAGE method in this studydetected PBVs only at high PBV excretion level conditionedby age (primary infection), and host physiologicalstatus, low PBV excretion levels were detected by RT-PCRthroughout the entire study period.The application of these methods allowed to establishthat PBVs are more widespread in nature than it was previouslydiscovered . In particular, a groupof researchers from the Netherlands when testing 83 stoolsamples from patients with diarrhea by RT-PCR confirmed17 samples positive for genogroup I PBV sequences (20 %). By the same method, a highproportion of PCR positive samples (23.4 %) was detectedin a total of 77 bovine fecal samples from different Brazilianregions analyzed . The highfrequency of infection in the sheep flock in Brazil evaluatedby RT- PCR was established where 62 % of the analyzedfecal samples were PBV-positive .Most researchers use two specific amplification strategiesto detect PBVs: the single and double primer PCRamplification strategies. The first amplification strategy isbased on the ligation of a viral RNA as a matrix with anoligonucleotide as an adapter, followed by the synthesisof cDNA on this matrix using a complementary adapterprimer. This method developed by Lambden et al. (1992)to carry out amplification of the viruses with segmenteddsRNA genomes was further used by researchers for theamplification of the PBV genome .In particular, Wakuda et al. (2005) applied the modifiedsingle primer strategy to prepare full-length cDNAs correspondingto RNA segments 1 and 2 of a human picobirnavirus(strain Hy005102).The single primer PCR amplification strategy is usuallyapplied to characterize full-length PBV genome segments.For PBV genotyping based on short genome specific fragmentsto characterize the strain with the definition of itsgenogroup, the second strategy of specific amplification isused, which involves the use of a pair of primers flankingthe selected viral genome fragment. Reverse transcription-PCR detection assays were developed with primers targetedto the genome segment of 2 PBV strains \u2013 4-GA-9 and1-CHN-97 isolated in the United States and China, respectively.In the case of human PBVs, the primers are targetedto specific conserved sites (motifs) in the PBV genomesegment 2 encoding RNA-dependent RNA polymerase.For detection of the genome group I, direct and reverse primers PicoB25 and PicoB43 are used, which flank the201 bp (in positions 665\u2013679 and 850\u2013865 of the segment2) fragment of the RdRp gene. To detect the genomegroup II, a pair of primers PicoB23 and PicoB24 flankingthe 369 bp (in positions 685\u2013699 and 1039\u20131053) fragmentof the RdRp gene is used.These primers can be used not only for human PBVgenotyping , but also for the geneticcharacterization of PBVs in some animals, in particularpigs . However, they are not able torecognize the full range of PBV strains circulating amonghumans, pigs, and other hosts due to their narrow specificity. In this regard,primers flanking other degenerated parts of the RdRp gene, as wellas primers with a wider range of detection of representativesof the genus Picobirnavirus, were later developed toexpand the specificity in detecting sequences of segmentsof the PBV genome .In particular, a RNA polymerase gene based RT-PCRdiagnostic assay was developed for detecting PBVs in earlystages of infection in a wide range of hosts including animalsand humans . Through RdRp genenucleotide sequences alignment analysis, the conservedregions of PBV were used for generating primers universalfor the genus. The best results for RT-PCR specificity andsensitivity were given by a primer set with sense primerPBV-7F (position 754\u2013771 of the segment 2), and antisenseprimer PBV-7R (position 1011\u20131028) flanking the275 bp amplicon. The developed assay made it possible toeffectively amplify this fragment of the RdRp gene in alltested PBVs infecting different host species, and did notgive false positive results when tested on other viruses.The use of primers with broad specificity, in additionto expanding the range of detection of representatives ofthe genus Picobirnavirus, allows amplifying sequencesof greater length. In particular, Ghosh et al. (2018) usinga wide-specific terminal primer, amplified a region of theRdRp gene overlapping several conserved sites and as aresult were able to characterize the complete genome segment2 of rat PBVs, providing important information ongenetic diversity and evolution of PBVs in rats.Recently, Kleymann et al. (2020) to detect PBVs fromdifferent mongoose species, have designed a pair of widelyspecific primers PBV 1.2FP and PBV 1.2RP that amplify asignificant part of the RdRp gene (1229 bp from ~1700 bp).This pair of primers allows detecting PBVs isolated fromdifferent hosts and having differences in primary structure. To identify genovariantsbelonging to the genogroup I among positive samples ofmongoose PBVs the authors used a combination of theknown reverse primer PicoB43 andthe forward primer PBV-7F, which allowed amplifying the390 bp fragment of the segment 2.In recent years, metagenomic analysis has become widelyused in the diagnosis of viral infections . The method of metagenomicanalysis is based on next-generation sequencing(NGS) technology that allows identifying all the geneticmaterial present in an environmental sample, consistingof the genomes of many individual organisms \u2013 metagenome.In contrast to PCR technologies that require referencesequences that can only detect known viruses, themetagenomic analysis method can detect viruses with anew genotype . Moreover, newgenotypes can be detected more often than known ones.The metagenomic analysis characterizes both the viraldiversity and the frequency of occurrence of individualmetagenome viruses. For example, according to Adriaenssenset al. (2018), the raw sewage metagenome containedrepresentatives of the genera Astroviridae, Caliciviridae,Picobirnaviridae, Picornaviridae, with only PBVs beingdetected in 100 % of raw sewage samples in this study. Inthe publication Boros et al. (2018) reported that using themethod of metagenomic analysis of the total number ofread sequences (13016) present in the metagenome, whichis a fecal sample of a chicken, in 516 reads were identifiedPBVs. In a study Yinda et al. (2019) using metagenomicanalysis of fecal samples from Cameroonian residents withand without signs of gastroenteritis (after contact withbats), found that up to 28 out of the 63 pools containedreads annotated as Picobirnaviridae with most of thepositive pools from individuals in age groups above 20.These facts indicate a fairly high level of PBV occurrencein wildlife.Summarizing the information presented in the review,obtained from publications on PBVs for the period understudy, we can conclude:PBVs are characterized by a broad host range and ubiquitousdistribution.The role of PBVs as causes of gastroenteritis is still notfully understood due to the lack of cell culture or animalmodels for their cultivation. This significantly impedesvirus isolation and clinical and pathological studies.The frequency of PBV detection varies in different studies,but it is found that it is associated with the physiologicalstatus and environmental conditions.There is a hypothetical explanation for the spread of PBVinfection based on the idea of PBVs as conditionallypathogenic viruses, according to which adult infectedhosts with normal immune status can be PBV carriersand serve as reservoirs of viruses without symptoms ofdiarrhea.The detection of PBV strains with genetically relatedgenome sequences in different animals indicates thepossible zoonotic nature of the infection for humans andthe ability of PBVs to transmit effectively.Being the most common in raw sewage, PBVs correlatebetter than other viruses with the presence of pathogenicviruses dangerous for humans in water bodies and arepotentially useful viral indicators of fecal pollution ofthese water bodies.PBVs are significantly different genetically. To date,5 PBV genogroups have been identified (GI\u2013GV).It has been suggested that PBVs can infect prokaryotes,being not mammalian viruses, but a new family of RNAbacteriophages. In support of this assumption, the authorsprovide convincing arguments showing that PBVs canactually infect prokaryotes, and not eukaryotes, in particular,bacteria Firmicutes. However, until a host isfound for PBV propagation, this assumption remainshypothetical.The presented information allows characterizing PBVsas viruses that are genetically variable with a broad hostrange, quickly evolving and easily spreading. However,for a more complete study of PBV biology, etiological rolein the occurrence of diseases, and pathogenic potential,experiments on gnotobiotic animals are required. 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Viral metagenomics analysisdemonstrates the diversity of viral flora in piglet diarrhoeic faecesin China. J. Gen. Virol. 2014;95(7):1603-1611. DOI 10.1099/vir.0.063743-0.Zhang S., Bai R., Feng R., Zhang H., Liu L. Detection and evolutionaryanalysis of picobirnaviruses in treated wastewater. Microb. Biotechnol.2015;8(3):474-482. DOI 10.1111/1751-7915.12239."} +{"text": "Correction to: Modern Pathology10.1038/s41379-019-0434-2th December 2019 without open access. With the authors\u2019 decision to opt for Open Choice the copyright of the article changed on\u00a03rd January 2020 to \u00a9 The Author(s) 2019 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.The article Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning, written by J. M. Bokhorst, A. Blank, A. Lugli, I. Zlobec, H. Dawson, M. Vieth, L. L. Rijstenberg, S. Brockmoeller, M. Urbanowicz, J. F. Flejou, R. Kirsch, F. Ciompi, J. A. W. M. van der Laak and I. D. Nagtegaal, was originally published electronically on the publisher\u2019s internet portal on 16"} +{"text": "Cytisus species. Cytisusaffinis, C.candidus, and C.spinescens nom. illeg., non Sieber ex Spreng. were described from Sicily by Karel Bo\u0159ivoj Presl, Cytisusspinescens was described from Apulia by Curt Polycarp Joachim Sprengel, and C.villosus was described from southern France by Pierre Andr\u00e9 C.villosus. The taxonomic revision of these five names confirmed that C.villosus Pourr. (= Cytisusaffinis C.Presl) is the name to be used for the species occurring in the large part of the Mediterranean countries. Cytisusspinescens Sieber ex Spreng. is the correct name for the amphi-adriatic species occurring in peninsular Italy, and along the NE coast of the Adriatic Sea. This species does not occur in Sicily and reference to this latter region in the protologues of both C.spinescens C.Presl and C.candidus C.Presl is a misinterpretation due, possibly, to exchange of labels.This paper deals with the typification and taxonomy of five Mediterranean Cytisus L. species and subspecies (C.striatus (Hill) Rothm., a naturalised alien in Liguria (C.hirsutus L. and C.villosus Pourr.); other taxa show a limited distribution and occur only in a few Italian regions , or are narrow endemics and PRC cited through the text follow We performed a survey of the original material in the herbaria Taxon classificationPlantaeFabalesFabaceaeC.Presl, Fl. Sicul.: XIX. 1826. [October 1826]3D593D16-2DA6-5713-9B35-42050A768163C.villosus Pourr., Hist. & M\u00e9m. Acad. Roy. Sci. Toulouse 3: 317. 1788. = \u201c[Sicilia]\u201d.Cytisusaffinis Presl. / In apricis regionis collinae Siciliae ad Panormum; in insula Capri ad Neapolim, etc., May 1817, s.coll. [C. Presl] s.n. : Italy. [The label written by K.B. Presl] 3!) Fig. .Taxon classificationPlantaeFabalesFabaceaeC.Presl, Fl. Sicul.: XIX. 1826. [October 1826]C9E338B3-A532-5346-B6CE-430BE7B50A63C.spinescens Sieber ex Spreng., Syst. Veg., ed. 16 3: 225. 1826. [January\u2013March 1826] \u2261 : \u201c[Sicilia]\u201d.Cytisuscandidus Presl. / Mons Garganus Apulia / collegit Sieber // [printed label of F.W. Sieber: PlantaeNeapolitanae et Apulae] Cytisusspinosus, Dec. Stachelicter Bohnenbaum. Auf felsigten nakten Stellen der S\u00fcdseite des Berges Gargano, May 1812, F.W. Sieber s.n. : Italy. [The label written by K.B. Presl] 17! Fig. , JE 000217! Fig. ).Taxon classificationPlantaeFabalesFabaceaeC.Presl, Fl. Sicul.: XIX. 1826. [October 1826] nom. illeg. (Art. 53.1. of the ICN)E4B17467-9873-5C11-BAE3-C2B4C62FBD2BCytisusspinescens Sieber ex Spreng. = Chamaecytisusspinescens Rothm., Feddes Repert. Spec. Nov. Regni Veg. 53(2): 143. 1944. [1 June 1944] \u2261 : \u201c[Sicilia]\u201d.Cytisusspinescens Presl non Spr. / Insula Capri et in Sicilia, a Schleichero et collegit Sieber. // [The label written by L. Thomas] Cytisusnanus Willd seu nova species / Calabre, s.d., s.coll. [L. Thomas] s.n. : Italy. [The label written by K.B. Presl] 71! Fig. , PRC 45282! Fig. , W 3339182! Fig. ).PR and PRC. After a detailed search for original material of the above mentioned names, we found seven specimens deposited in PR and PRC putatively belonging to different gatherings and identified as three distinct taxa. We found two specimens of C.affinis C.Presl , locality, collector and a short diagnosis against C.triflorus L\u2019H\u00e9r. In addition, there is attached a small label from Presl\u2019s exsiccata collection \u201cFlora sicula\u201d, suggesting that duplicates of this collection were distributed in the past and can be found elsewhere. Both specimens look very similar in respect of phenology and form of preparation and although they differ in the month of collection (May versus April), this likely originates from labelling of specimens in different times, and both specimens could be part of a single gathering. Both specimens are original material. They bear the name \u201cCytisusaffinis Presl\u201d written by himself, and in this case it seems unquestionable that the name C.affinis is based on specimens collected by Presl in Sicily. In any case, bearing two different dates, we prudentially consider them as two different gatherings. As the specimen in PRC , a species currently accepted under the name C.villosus Pourr. (see below), in his unpublished and undated second volume of Flora Sicula.During his professional life, K.B. Presl worked simultaneously as curator of Prague National Museum collections [at that time Patriotic Museum in Bohemia] (1823\u20131846) and in various positions in other Prague institutions . At the 903 Fig. , PR 3754413 Fig. ) collectPRC Fig. bears a PRC Fig. . The spe PR Fig. bears a PRC Fig. is more Cytisuscandidus and C.spinescens. We have found one specimen belonging to Cytisuscandidus in PR (PR 375660!) Thomas (1784\u20131823) in the region of Banat (currently in Romania and Serbia) .In addition, in W there is a sheet W333912 photo!) Fig. bearing a Sicula , and occurs , bearing the original label from Sieber\u2019s \u201cPlantaeNeapolitanae et Apulae\u201d collection, as the lectotype of C.candidus C.Presl. The specimen PRC 454917, as well as the duplicates in JE and W, are therefore isolectotypes of C.candidus C.Presl.In the case of 660 Fig. bears, i) occurs . Interes PRC 45497, Fig. 1PRC Fig. . We herePR 375417 ).Based on the morphology of the specimens of Presl\u2019s Spreng. , 1985, aDatabase and in Elantbase . ConcernTaxon classificationPlantaeFabalesFabaceaeSieber ex Spreng., Syst. Veg., ed. 16 3: 225. 1826. [January\u2013March 1826]786F91FA-28F7-5A11-B6A5-BC000F1AB011Spartiumspinescens (Sieber ex Spreng.) Bertol., Fl. Ital. 7(3): 345. 1850. [June 1850] \u2261 Cytisuscandidus C.Presl \u2261 [after typification] \u201cMons Garganus Apul.\u201d Puglia.Cytisuscandidus Presl. / Mons Garganus Apulia / collegit Sieber // [printed label of F.W. Sieber: PlantaeNeapolitanae et Apulae] Cytisusspinosus, Dec. Stachelicter Bohnenbaum. Auf felsigten nakten Stellen der S\u00fcdseite des Berges Gargano, May 1812, F.W. Sieber. s.n. : Italy. [The label written by K.B. Presl] 17! Fig. , JE 000217! Fig. ).PR, W and JE, and as shown above also in PRC, although incorrectly labelled later by Presl. It is interesting to note that Presl based his later homonym C.spinescens on a different gathering (Thomas\u2019 collection), while he described C.candidus on a F.W.Sieber\u2019s gathering. As the above designated lectotype of C.candidus belongs, without any doubt, also to the original material of C.spinescens Sieber ex Spreng, we designate it also as the lectotype of the latter name. Cytisuscandidus C.Presl thus becomes a homotypic synonym of the prioritary name C.spinescens Sieber ex Spreng.As Sprengel based his description on the exsiccata series collected and issued by F.W. Sieber, the best solution for typification would be to choose the specimen from Sieber\u2019s collection seen by Sprengel himself. Unfortunately, after the death of his son, Sprengel\u2019s rich herbarium was divided into many parts and sold in small portions to different specialists and institutions . The larC.spinescens Sieber ex Spreng. as a member of the separate genus Chamaecytisus Link, the correct name is Chamaecytisusspinescens Rothm. This is because This brings also another nomenclatural consequence: when treating Taxon classificationPlantaeFabalesFabaceaePourr., Hist. & M\u00e9m. Acad. Roy. Sci. Toulouse 3: 317. 1788.3CE5CA0F-7251-5287-9D00-BBCE1AE53847Cytisustriflorus L\u2019H\u00e9r., non Lam., nom. illeg. \u2261 [after typification] \u201cAux environs de Narbonne, \u00e0 Fontlaurier\u201d. Frances.d., R. L. Desfontaines, s.n. .: Algeria. In montibus prope Algeriam, Chlorisnarbonensis\u201d), where Pierre Andr\u00e9 Pourret\u2019s (1754\u20131818) collections are mainly kept as the lectotype of C.triflorus L\u2019H\u00e9r. [1791]; an illegitimate name (a later homonym of C.triflorus Lam. [1786]) being conspecific with C.villosus Pourr. , it becomes automatically a homotypic synonym of Cytisusvillosus Pourr. \u2013 which is the accepted name of the generitype of this genus.We did not find any original material for this name either in MAF (MAF-Pourret collection), and P (the general collection and the special Pourret\u2019s collection named \u201cnly kept , or in only kept : 368. Itnly kept , followenly kept : 368. Be"} +{"text": "Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999-2013.Wu B., Zhang, L., Liu Z., He H., Pan A., Wang F., Zhang M., Chen B., Lu Z., Chen S and Wang X. 2017. http://dx.doi.org/10.1080/16549716.2017.1293925The following line was omitted from the version originally published online:Joint first authors, B.W and L.Z, contributed equally to this article.This information has now been re-instated in the acknowledgements section and indicated as a footnote on the first page.Taylor and Francis apologizes for this error."} +{"text": "Generally, neuropsychiatric patients share different symptoms across nosological categories, such as, amongst other, psychological distress, mood alterations, anxiety, and self-regulation disturbances.ReAttach is a novel psychological intervention with its key elements being external affect and arousal regulation, stimulation of multiple sensory processing, conceptualization, affective mentalization, and associative memory processing. ReAttach has been hypothesized to be effective in reducing symptom severity in different psychiatric conditions. Given the limited information currently available, the present study aimed to investigate the effect of main ReAttach elements called \u201cWiring Affect with ReAttach\u201d (W.A.R.A.) on negative affect (N.A.), and to compare it with \u201cDistraction,\u201d another well-established affect-regulating strategy.We used a single-blind, randomized controlled crossover equivalence design to compare the efficacy on N.A. regulation of W.A.R.A. versus Distraction in 101 patients with different neuropsychiatric disorders.The results showed a significant difference (p < 0.001) in response to W.A.R.A. vs. Distraction, with W.A.R.A. being significantly more effective in regulating N.A., with a large effect size (dRMpooled = 2.38) and a high probability (95%) of success.The heterogeneity of the study population makes generalization and clear recommendations for specific patient groups difficult. The Numeric Rating Scale might have prevented detection of increased N.A. when the baseline scores were high. More in-depth research is needed to explore the W.A.R.A. technique and the extent of confounding variables such as the placebo effect.The findings suggest that W.A.R.A. may be an effective, accessible, and brief intervention reducing negative affect. Although premature, these first results are encouraging. Psychology; Clinical psychology; W.A.R.A.; Distraction; ReAttach; Affect regulation; Emotion regulation; Neuropsychiatric Disorders Affect During N.A. regulation, unpleasant internal and external sensory stimuli need to be integrated, identified, and conceptualized as emotion or pain . The rolReAttach is another psychological intervention, in which environmental affect and arousal regulation, multiple sensory stimulations, and social cognitive training are combined . PracticW.A.R.A. is a sub-element of ReAttach, explicitly aiming at wiring unpleasant feelings to a sizeable neural ensemble, actively composed by the therapist through simultaneous activation of multiple concepts under ReAttach conditions .This pilot study aimed to investigate the efficacy of W.A.R.A. on N.A. in a single-blinded randomized controlled setting versus Distraction in different neuropsychiatric conditions.22.1We used a single-blind, randomized controlled, crossover equivalence design, to compare the efficacy on N.A. regulation of W.A.R.A. versus Distraction in Dutch patients with different neuropsychiatric disorders. The group of patients experienced problems in daily life functioning, such as dealing with stressful events, self-regulation, and executive functioning. The data were sampled as part of care as usual in Dutch clinical therapeutic settings, and therefore permission from the medical ethics review committee was not required. The trial was carried out by the ReAttach Therapy International Foundation in the Netherlands.A priori power analysis was performed in G. Power to calcureattachregister.org). Fifty-six patients had been diagnosed by a psychiatrist, (neuro)psychologist, or neurologist, as shown in Patients were 101 adult patients with neuropsychiatric disorders recruited by 13 qualified Dutch ReAttach therapists with a private practice or B (first W.A.R.A. and secondly Distraction) with a random plan generator as followed: therapist 1, 5, 7, 8, 9 and 12 were assigned to group A, and 2, 3, 4, 6, 10, 11 and 13 to group B. Subjects could leave the study at any time for any reason without consequences.2.1.2Two self-administered questionnaires were designed including questions about demographics, therapist instructions, and questions about NA at different time points. One survey included instructions and measurements for group A (first Distraction and secondly W.A.R.A.) and another questionnaire for group B (first W.A.R.A. and secondly Distraction). All therapists received a personal hyperlink leading to the survey for either group A or B. The therapists and patients knew that Distraction and W.A.R.A. were offered as extra tools to regulate NA. They were blind to the sequence and comparison of both interventions. As a result of the randomization and anonymous data sampling, the researcher was blind to the assignment of patients. 2.2reattachregister.org) provided W.AR.A. and received online instructions on how to provide Distraction. Psychopharmacological treatment was allowed since medications remained stable during this study, which lasted only one therapy session.Qualified ReAttach therapists . Then the therapist changed the tapping speed again into fast tapping, to activate optimal arousal to process the next instruction: to remember the exercise so far. Immediately after this instruction, the therapist changed tapping speed again towards low arousal. During the low arousal, the therapist remained silent for 20 s. The therapist ended the W.A.R.A. exercise under fast tapping conditions by the instruction to open the eyes.2.3At the beginning of the therapy session (T0), patients of both groups were asked to focus on NA and rate the intensity of unpleasantness on an 11 points numerical rating scale, commonly used to evaluate the severity of pain . InsteadAfter the baseline rating, subjects from group A received Distraction, and patients from group B received W.A.R.A. Both interventions took approximately the same amount of time: between 60 and 90 s. Immediately after the first intervention (T1), the therapists asked the subjects if the unpleasant feeling was still present or gone. Descriptive statistics with percentage values of frequencies indicated that immediately after the intervention (T2), 20% of the subjects after Distraction, and 74% of the patients directly after W.A.R.A claimed that the unpleasant feeling was gone, as presented in After re-engagement with the feeling, 18.2% of the subjects who received Distraction as the first intervention and 26.1 % of the individuals who received W.A.R.A., stated that the unpleasantness was less intense or changed. As presented in Immediately after the second rating (T2), the remaining subjects from group A received W.A.R.A. as a second intervention, and the remaining subjects from group B received Distraction as a second intervention. After the second intervention, all subjects were asked to refocus on the negative feeling and to rate the intensity of unpleasantness for the third time (T3). The zero scores at T2 from subjects who partially dropped out were carried on to T3 due to the intention to treat procedure. 2.4Descriptive statistics and a Consort Flowchart were used to contextualize the demographic characteristics of the study population. We used the Mann Whitney U Test, Wilcoxon Signed Rank Test, and one-way ANOVA for comparison of demographic characteristics and outcome measures between the groups at baseline. Mann-Whitney U test was used for comparison of intervention outcome between groups. A Friedman test was run to compare intervention for the within-subjects design. Pairwise comparisons were performed . Effect-sizes for the intervention outcomes within-subjects were estimated by single group pre-test post-test design by taking the correlation between pre- and post-test into account . All sta33.1As shown in The Mann-Whitney U test indicated that there was no significant difference between group A (mean rank 49.50) and B (mean rank 52.79) at baseline NA rating.3.22(5) = 339.743, p < 0.005. Negative affect was significantly different at the different time points, X2(2) = 193.729, p < 0.001. The post-hoc analysis revealed that W.A.R.A. (Mdn = 7.00) was statistically significantly more effective than Distraction (Mdn = .00) (p < 0.001), with a large effect size for W.A.R.A. and a medium effect size for Distraction .The intervention outcome was statistically significantly different between the interventions, XIn group B only 13 subjects received Distraction. The NA had disappeared after W.A.R.A.; therefore, 33 out of 46 subjects could not bring the NA up again and did not receive Distraction as a second task. In the group A (N = 55) where Distraction was the first intervention, the mean difference between the pre-test and post-test was 0.72 and in group B (N = 46) where Distraction was offered as the second intervention the mean difference was 0.50 .The distribution of Distraction was similar in both groups, as assessed by visual inspection. The efficacy of Distraction was not significantly different between group A (Mdn = .00) and group B , with medium effect sizes for group A (dRMpooled = 0.42) and group B (dRMpooled = 0.36) The distribution W.A.R.A. was similar in both groups, as assessed by visual inspection. The efficacy of W.A.R.A. was not significantly different between group A (Mdn = 7.00) and group B with large effect sizes for group A (dRMpooled = 2.173) and group B (dRMpooled = 2.681). Evaluation of the intervention outcomes in terms of success (positive change) or failure (no change or negative change) resulted in a probability of success for W.A.R.A. of 95%. The likelihood of success for Distraction was 26.7%.4The present study aimed to investigate the efficacy of W.A.R.A., an affect regulation strategy, based on disengagement , throughThe results of this study revealed that W.A.R.A. was significantly more beneficial with a large effect size (dRMpooled = 2.38), as compared with Distraction with a medium effect size (dRMpooled = 0.38).After W.A.R.A., 89% of the subjects reported that the N.A. was less intense/had changed (26.1%) or was gone (67.4%). We found a carryover order effect after W.A.R.A. as the first intervention, but not after Distraction as the primary intervention. Therefore, a secondary outcome of the study was that, in contrast to W.A.R.A., the effect of Distraction was temporary. Re-engagement with the N.A. after the distractive task caused a revival of the unpleasant feeling in all patients. After re-engagement, no subject claimed that the negative feeling had disappeared after Distraction. A vast majority of the Distraction patients (82 %) reported that after re-engagement, the N.A. had not changed at all. The remaining Distraction patients (18.2%) indicated that the intensity or the feeling had changed in the meantime. Internal or external change in arousal might have caused these changes in intensity since arousal was co-regulated by the presence of the therapist.It is not taken for granted that patients agree to the tapping on the hands. W.A.R.A. requires proximity to the therapist and the patient's trust. Before any treatment can be offered, the ReAttach therapist will have to invest in a good working relationship with the patient. It is common practice and necessary to provide basic information about ReAttach and individually pay attention to the multiple sensory stimulations, the arousal regulation, and to the associative nature of ReAttach. Since W.A.R.A. consists of the essential elements of ReAttach, it makes the exercise particularly suitable as a first introduction of the ReAttach intervention. Therefore, W.A.R.A. is scheduled before the start of the first ReAttach session.In this study, all participants went along with the tactile stimulations, probably due to the explanation of the intervention, and the predictability of the touch. It is an interesting phenomenon that W.A.R.A. can be used to reduce tactile over-responsivity. Patients with resistance to the proximity of the therapist or to physical contact, receive self-regulation exercises. W.A.R.A. can be provided as a self-regulation tool. This study focuses exclusively on W.A.R.A. provided by the therapist. Another research is currently investigating the efficiency of W.A.R.A. provided as a self-regulation tool versus W.A.R.A. face to face by the therapist.The conceptualization of negative affect in unpleasant feelings may still be a point of discussion. During the W.A.R.A. instruction, language is essential. The therapist is instructed not to visualize or conceptualize the unpleasant feelings for the patient to be able to address pre-conceptual negative affect: it is only referred to as an unpleasant feeling. The grouped words needed to build a temporary ensemble of concepts may be randomly chosen. To make W.A.R.A. a pleasant intervention, the therapists are instructed to select positive concepts that fit the patient's world of experience.Besides W.A.R.A., that in the current study showed a superior outcome effect compared to Disengagement, Eye Movement Desensitization and Reprocessing (E.M.D.R.) therapy, which is similar to Disengagement in terms of taxing the working memory, also proved to be effective in terms of reducing N.A. . The taxThe present study suffers from several limitations that should be acknowledged. First, the heterogeneity of the research population makes it challenging to interpret the study outcomes and to give clear recommendations for specific patient groups. Second, we used a Numeric Rating Scale, initially designed for the evaluation of pain , to rate5Although carried out in a single-blinded, controlled design, the study must be considered to be a pilot. Nevertheless, the results would suggest that W.A.R.A. may be an effective, accessible, and short transdiagnostic intervention for the reduction of N.A. in different neuropsychiatric disorders. Again, W.A.R.A. seemed without short-term revival after re-engagement. As compared with Distraction, a self-regulation exercise with a temporarily medium effect, W.A.R.A. was found to be significantly more beneficial. However, our findings require to be replicated in larger samples of patients with specific neuropsychiatric conditions, and/or to be corroborated by follow-up data to explore how long W.A.R.A. effects might last. Our opinion is that W.A.R.A., and other psychological techniques if substantiated by further data gathered in controlled trials, would constitute accessible, gentle, and evidence-based transdiagnostic interventions for specific symptom clusters present in a wide range of different neuropsychiatric conditions.P. Weerkamp-Bartholomeus: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.E. Chan, A. Srivastava: Conceived and designed the experiments; Wrote the paper.D. Marazziti, T. Van Amelsvoort: Analyzed and interpreted the data; Wrote the paper.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors declare the following conflict of interests: P. Weerkamp-Bartholomeus designed both ReAttach and W.A.R.A.No additional information is available for this paper."} +{"text": "Aedes sierrensis (Diptera: Culicidae) J. Insect Sci.\u201dCorrection of \u201cChaves L. F., N. Reissen, G. S. White, S. Gordon, and A. Faraj. 2020. Trap Comparison for Surveillance of the Western Tree Hole Mosquito, DOI: 10.1093/jisesa/iez131During the processing of this article, a miscommunication between the author and the publishing team resulted in the title appearing incorrectly in the initial published version online. The title has been corrected."} +{"text": "Since the outbreak of the COVID-19 pandemic and its social restriction measures, online therapy is a life-saving possibility for patients with acute stress. Wiring Affect with ReAttach (W.A.R.A.) is a brief psychological intervention aiming to decrease negative affect, that can be offered online.We assessed the effect of remote W.A.R.A. on negative affect in 37 patients. Consequently, we compared the effect of remote W.A.R.A. versus face-to-face W.A.R.A on negative affect in a cross-sectional design.d = 3.08, p < 0.001). However, the reduction on negative affect was smaller than with W.A.R.A. face-to-face. We found a substantial difference between W.A.R.A. remote therapy and W.A.R.A. face-to-face in decrease of negative affect .W.A.R.A. remote therapy provoked a significant reduction of negative affect with a large effect size (The major limitation of the pilot-study is the sample size of 37 patients. Besides, we designed a numeric rating scale for evaluating negative affect. We investigated the impact on negative affect by assessing \u201cunpleasant feelings.\u201d This conceptualization of negative affect might still be a point of discussion.The study\u2019s findings indicated that W.A.R.A. remote therapy significantly reduced negative affect, but to a lesser extent than W.A.R.A. face-to-face. Nevertheless, W.A.R.A. remote therapy might offer a fast relief, especially when personal contact is difficult. The COVID-19 outbreak is an urgent concern for mental health around the world, in addition to the threat to physical health. The pandemic\u2019s impact on psychological and physical health will be devastating unless we provide our patients with a therapy or self-regulation strategy to dampen the acute stress response . Indeed,Accessible forms of psychotherapy that can help to alleviate the initial psychological distress may prevent the development of post-traumatic stress disorders, obsessive-compulsive disorders, depression, and social anxiety . Online By providing online self-regulation strategies, such as Wiring Affect with ReAttach (W.A.R.A.) remote therapy, psychologists might be able to guide patients into the downregulation of their psychological distress. Hence, as soon as the COVID-19 pandemic began, we started to give free online W.A.R.A. remote therapy courses to provide this potential first-aid psychological intervention to professionals worldwide .Wiring Affect with ReAttach is a brief psychological intervention, generally provided by trained ReAttach therapists for patients struggling with persistent complaints of negative feelings and sensory over-responsivity, aimed to decrease negative affect , 2020a. Wiring Affect with ReAttach refers to \u201cWiring Affect with ReAttach\u201d because the exercise is part of the extended ReAttach procedure, which we will briefly describe. ReAttach is an accessible, tailored, transdiagnostic intervention based on the activation of healthy development, aiming to help children and adults to become the best possible version of themselves and contWiring Affect with ReAttach is made up of essential elements of ReAttach, such as arousal regulation, sensory stimulation, multiple sensory processing, and associative memory formation . During Due to its accessibility and simplicity, W.A.R.A. might serve as a self-regulation tool provided by remote therapy.Although previous studies assessed the effectiveness of W.A.R.A. performed by a therapist through face-to-face contact, no research has yet been conducted into the application of W.A.R.A. delivered online. We examined the efficacy of remotely delivered W.A.R.A. in the reduction of negative affect and compared the results of the W.A.R.A. remotely provided with results of W.A.R.A. face-to-face by a therapist.In the period of lockdown, Dutch qualified ReAttach therapists, professionally educated in psychology, occupational or physical therapy, offered 37 patients with stress-related complaints online guidance. These ReAttach therapists all participated in the free online W.A.R.A remote therapy training. Since ReAttach therapy is not suitable for online treatment, they offered W.A.R.A. remote therapy as a guided self-regulation tool to decrease negative affect as part of online consultation. Reported suicidality risk and alcohol or drug abuse at the time of the online consultation were exclusion criteria for W.A.R.A. remote therapy according to the standard ReAttach procedures .The data were collected as part of routine clinical care, and therefore no research ethical committee approval was necessary. All the patients consented to data use for research purposes. Online assessment took place before and after W.A.R.A. remote therapy referring to one online video consultation.Information about patients\u2019 diagnoses and medication is listed in Qualified ReAttach therapists provided W.AR.A. conform trained protocol , 2020a. For the remote therapy we simplified the W.A.R.A. instruction. By remote instruction, the patient needs to adopt several skills that the therapist normally performs, such as sensory stimulations (tapping) and arousal regulation by change of tapping speed. Therefore, we chose to simplify the tapping technique which we normally use for the downregulation, to gently pressing on a surface. At first the patients learned how to optimize arousal for multiple sensory processing and dampen unpleasant feelings through tactile stimulation. The fast tactile stimulation at the beginning of W.A.R.A. and during the instruction of memory formation, remained the same. The students of the W.A.R.A. remote therapy course learned to tap fast as soon as they heard the word \u201ctap\u201d and downregulate as soon as they heard \u201cstop.\u201d During W.A.R.A. face-to-face, the therapist delivers a tailored intervention by adapting the voice and choice of positive concepts that appeal to the patient. During the W.A.R.A. remote therapy course, no such adjustment was made. We decided to offer every professional the same video instruction with similar positive concepts during low-frequency tapping . Also, we offered recorded voice instructions on-line as an aid for W.A.R.A. self-regulation.All patients received the same questionnaire to score negative affect before and after the intervention. We conceptualized negative affect as \u201cunpleasant feeling,\u201d rated on an 11-point numeric rating scale developed for by us. At baseline, the patients rated an unpleasant feeling on a scale of 0 to 10 (most unpleasant). After this baseline measurement, they received the intervention with was either W.A.R.A. face-to-face or W.A.R.A. remote therapy. After the intervention, we immediately asked the patients if they could still feel this unpleasant feeling: yes or no. Finally, we asked these patients to re-engage with the negative affect and again rate the unpleasantness.We used descriptive statistics and a Consort Flow-chart to contextualize the demographic characteristics and the flow of the patients. With the Wilcoxon Signed Rank Test, we compared the baseline and post-test negative affect ratings within-subjects. We used one-way ANOVA for comparison of demographic characteristics and mean affect rating at baseline between groups. To assess the differences in outcome between groups, we used the Mann\u2013Whitney U test. Pairwise comparisons were performed . The staF = 1.492, p = 0.225, gender F = 0.113, p = 0.737 or baseline sore F = 0.049, p = 0.825 between the W.A.R.A remote therapy group and the W.A.R.A. face-to-face group.As shown in z = \u22125.10, p < 0.001. The effect size was large, d = 3.08 after W.A.R.A. remote therapy (Mdn = 3.00), compared to the negative affect before the intervention (Mdn = 7.00), d = 3.08 . Evaluatz = \u22125.144, p < 0.001. The difference in reduction of negative affect was large d = 1.36 (p < 0.001).We compared the data from the W.A.R.A. remote therapy group versus the data from 46 patients from a previous W.A.R.A. face-to-face by therapist study . As showThis pilot study aimed to find out whether W.A.R.A remote therapy might represent a valuable first-aid psychological intervention. According to us, this is particularly relevant at this time of COVID-19 pandemic. During this uncertain and challenging time, stress, and anxiety increase because we are all concerned about the magnitude and effects of this crisis . In timeWe examined the effect of W.A.R.A. remote therapy on negative affect and compared the reduction of negative affect of W.A.R.A. remote therapy versus W.A.R.A. face-to-face. W.A.R.A. remote therapy resulted in a significant decrease in negative affect with a large effect size. However, we found a larger reduction of negative affect after W.A.R.A. face-to-face compared to W.A.R.A. remote therapy.We pose several potential explanations for the fact that W.A.R.A. remote therapy was less successful than the W.A.R.A. face-to-face. First of all, it is much easier for a therapist to influence complex transdiagnostic processes such as co-regulation of arousal and affect face-to-face than by online therapy. Furthermore, the timing, a crucial element during W.A.R.A., is more difficult to achieve by online guidance. We also think that the real proximity enhances the patient\u2019s trust and might induce more positive expectations about the intervention outcome; W.A.R.A. face-to-face might induce more placebo-effect. Moreover, we believe that it is not apparent for patients with stress-related complaints to have either neutral or positive expectations about their self-regulation abilities. Their elevated stress-levels will more likely induce negative expectations, which may lead to nocebo-effects, especially without the physical presence and re-assurance of a therapist.The results of this pilot study suggest that even for a brief and accessible self-regulation exercise as W.A.R.A., face-to-face interaction with a therapist is more effective. W.A.R.A. face-to-face is also more favorable, considering the various ethical arguments against engagement in online psychotherapy such as privacy, confidentiality, and emergency issues .The availability, rapid transferability, lightness of the intervention, and efficiency of W.A.R.A in decreasing negative affect should be strongly highlighted. The fact that the intervention can be used as a self-regulation tool also makes the application of W.A.R.A. remote therapy even more interesting. If we can actually train patients to use W.A.R.A. as a self-regulation technique, this will no doubt contribute to enhance their autonomy and self-control.Wiring Affect with ReAttach remote therapy can be compared with other short-term online self-help interventions, such as Compassion-Focused Therapy and otheSince W.A.R.A. can be trained as a self-regulation technique, W.A.R.A.\u2019s more frequent practice might improve stress-resilience in vulnerable patients. For more extended online therapies such as Online Group Schema Therapy Based Day-Treatment , W.A.R.AWe would acknowledge a criticism of the technique: W.A.R.A. remote therapy is beneficial as a strategy to deal with unpleasant feelings, sensory over-responsivity and psychological distress, but it cannot solve more severe mental health problems . ReAttacWiring Affect with ReAttach is an innovative non-invasive psychological intervention by which negative affect can be reduced effectively.This pilot study suffers from several limitations that should be mentioned, such as the small sample size and the design of the numeric rating scale, that was based on a numeric rating scale for the evaluation of pain . AlthougIn the near future, we would like to investigate the application of W.A.R.A. for specific patient groups. Since W.A.R.A. can be trained as a self-regulation technique, more frequent practice of W.A.R.A might improve stress-resilience in vulnerable patients. We think that it would be very interesting to investigate such W.A.R.A. training in a randomized controlled design with follow-up measurements.Wiring Affect with ReAttach, usually provide face-to-face by a ReAttach therapist, can successfully be provided as remote therapy and significantly reduce negative affect. Although W.A.R.A. face-to-face is more favorable and more effective, these first results of W.A.R.A. remote therapy are encouraging. Besides, W.A.R.A. is accessible, and online training for professionals is free. Furthermore, W.A.R.A. remote therapy can be learned as a self-regulation technique. Extended research with a larger sample size and with specific patient groups is needed to assess the full potential of W.A.R.A. face-to-face and W.A.R.A. remote therapy.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Since data were collected as part of routine clinical care, no research ethical committee approval was necessary. All patients consented to data use for research purposes.All authors contributed to the conception and design of the study. PW-B collected and analyzed the data and wrote the manuscript. All authors contributed to the manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GO declared a shared affiliation, with no collaboration, with one of the authors DM to the handling editor at the time of the review."} +{"text": "Asian-Australas J Anim Sci 2018. Vol 31, No. 5 : 748\u2013754.The followings are to be changed in"} +{"text": "Scientific Reports 10.1038/s41598-018-27131-8, published online 11 June 2018Correction to: Shin-ichi Koda was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:A.M. and S.A. designed the experiments. A.M. conducted biochemical and fluorescence experiments and analyzed the data with inputs from S.K. J.A. screened initial crystallization condition. Y.F., J.A. and S.A. collected the diffraction data and analyzed the structures with inputs from E.Y. Both A.M. and S.A. drafted the manuscript with input from all authors."} +{"text": "Stenhelmoides Grouvelle is a Neotropical genus of Elmidae and although it exhibits a wide distribution, until now no larvae had been associated with adults of this genus. Larvae, very likely belonging to this genus, were associated based on co-occurrence with adults. Eleven larvae and nine adults were examined from ten localities at altitudes between 30 and 682\u2009m a.s.l. in the Andean, Caribbean and Pacific regions in Colombia. Mature larvae of the Stenhelmoides rufulus (Hinton) are described and illustrated for the first time. A larval diagnosis for the genus is presented; body shape, distribution and form of setae and number of pleural sclerites are diagnostic characters for larvae of this genus. Comparative notes with similar larvae of other Elmidae genera are presented. The existing generic keys are updated to include larvae of Stenhelmoides. Comments on distribution and habitat of Stenhelmoides larvae are also provided. This work contributes to enhance the knowledge of Neotropical larvae, which have been described for only approximately 56% of genera and 8% of species of Elmidae. They are considered effective bioindicators of water quality and commonly used in ecological studies. Both larvae and adults are found in freshwater ecosystems; however, the immature stages of Elmidae are poorly known. Even though elmid larval knowledge is not complete, several improvements have been achieved in recent years. In the first place, several keys that allow identification of Elmidae larvae have been produced5. Description of larvae belonging to several genera and species have also been published: Austrelmis catamarcensis Manzo & Archangelsky, 20156, Austrelmis talampayensis Manzo & Archangelsky 20156, Austrelmis uaik Mart\u00ednez-Rom\u00e1n, Archangelsky & Manzo, 20177, Austrolimnius nyctelioides 8 and A. elatus Hinton, 19418, Luchoelmis kapenkemkensis Archangelsky & Brand, 20149, Macrelmis pubescens 10, Neblinagena mira \u010ciampor, \u010ciamporov\u00e1-Za\u0165ovi\u010dov\u00e1 & Kodada, 201711, Phanoceroides aquaticus Hinton, 193912, P. fernandesi La\u0161\u0161ov\u00e1, 201612, Stethelmis shepardi Mart\u00ednez-Rom\u00e1n, Manzo & Archangelsky, 201913, Typhloelmis caroline Barr, 201514, T. finegan Barr, 201514 and T. sanfelipe Barr, 201514. Finally, molecular techniques have been useful to perform larval and adult associations16, these were first used for assigning the larva of Hedyselmis opis Hinton, 197617Riffle beetles are common dwellers of running waters and constitute an important component of benthic macroinvertebrate communities18. Furthermore, larval characters in phylogenetic studies can successfully be used to solve relationships among taxa20.A better larval knowledge and a higher taxonomic resolution can support the use of riffle beetles in a wider range of fields such as biogeography, and significantly enhance their use as environmental bioindicators in ecological studies21. One of those Neotropical genera is Stenhelmoides Grouvelle, 1908, with 15 described species and a wide geographical distribution. It is recorded in 15 countries from southern Mexico to Brazil, at altitudes between 100 and 2900\u2009m a.s.l.22. However, the wide distribution of this genus is primarily a reflection of occurrence of a single species; Stenhelmoides rufulus . The remaining 14 species are present in South America, mainly in lowlands of the Amazon region23.The Neotropical region is characterized by a high-level of endemism and great diversity of Elmidae with around 50 genera and 500 speciesStenhelmoides are distinguished from other Elmidae by the following combination of characters: dorsal tomentum over pronotum and elytra, with an oval area without tomentum in the middle of pronotum, the lack of carinae or depressions on pronotum and the presence of granulose rows on elytra without forming carinae22.Adult Stenhelmoides was undescribed. The same can be said for several other genera of Neotropical riffle beetles, therefore a detailed revision of distributional data was performed in order to rule out the possibility that this larva could belong to another genus. In Colombia 29 genera of Elmidae have been reported , additionally these larvae and their adults are small and unlike Stenhelmoides, they are frequent and abundant in sampled streams, something that facilitated their association. On the other hand, Stenhelmoides is uncommon and the studied material comes from a few museum specimens, and no fresh material has been available to perform molecular associations, or even to try to rear them. We also considered all elmid genera found in the same locations where Stenhelmoides specimens were collected, and all of them had known larvae. Taking in account the co-occurrence of these larvae with adults of Stenhelmoides rufulus, the larvae here described can be assigned to this species with a good degree of confidence.Prior to this contribution, the larva of ed Table\u00a0, but onles Table\u00a0. Larvae Other genera with unknown larvae found in neighboring countries Table\u00a0 correspo24 and Helicon Focus\u00ae. The larval morphology nomenclature of Harris25, Shepard26, Borror et al.27, Lawrence28 and Kodada et al.1 were followed for the descriptions. Data on physical and chemical parameters of Stenhelmoides habitats were provided by the Water Laboratory of Institute for Research and Development in Water Supply, Environmental Sanitation and Water Resource Conservation - CINARA (by its acronym in Spanish) of Universidad del Valle .Specimens were captured with a Surber net, killed and preserved in a 75% ethyl alcohol solution. Larval specimens were cleared using warm lactic acid and dissected and mounted on glass slides with PVLG medium. Observations were made using a Leica S6D dissecting microscope and a Leica DMLB compound microscope, both equipped with photographic cameras. Drawings of setae were scanned and digitally edited. Additional photographs Fig.\u00a0 were takMUSENUV\u2009=\u2009Museo de Entomolog\u00eda de la Universidad del Valle, Cali, Colombia.CLCH\u2009=\u2009Colecci\u00f3n Limnol\u00f3gica de la Universidad Tecnol\u00f3gica del Choc\u00f3, Quibd\u00f3, Colombia.CMA-UCO\u2009=\u2009Colecci\u00f3n de Macroinvertebrados Acu\u00e1ticos de la Universidad Cat\u00f3lica de Oriente, Rionegro, Colombia.COMAC-SINCHI\u2009=\u2009Colecci\u00f3n de Macroinvertebrados Acu\u00e1ticos de la Amazon\u00eda Colombiana, Leticia, Colombia.IAvH-E = Colecci\u00f3n Entomol\u00f3gica del Instituto de Investigaci\u00f3n de Recursos Biol\u00f3gicos Alexander von Humboldt, Villa de Leyva, Colombia.. Head exposed or partially concealed by pronotum, capable of being retracted into prothorax; frontal lines Y-shaped, merging basally into a long coronal line, about 1/4 of head; stemmata absent; clypeus concave without anterolateral tooth; labrum oval, wider than long; antenna with three antennomeres, second antennomere longer than other two together, with antennal sensorium long, as long as or slightly longer than second antennomere; mandibles symmetrical, with three apical teeth; prostheca long; maxilla with stipes longer than palpus, with four palpomeres; galea entire; lacinia well-developed, fused to stipes; labium with postmentum three times longer than prementum, palpi with two palpomeres, inserted on a short palpiger. Prothorax with six ventral sclerites, one antero-lateral pair and two lateral pairs, procoxal cavities open and membranous; meso- and metathorax with seven ventral sclerites, three large anterior process-like sclerites and two lateral smaller pairs, coxal cavities open; meso- and metathoracic sternal sclerite strong and prominent between coxae. Abdomen with a single pair of pleural sclerites on first segment; sternopleural and tergopleural sutures incomplete on second abdominal segment; abdominal segments wider than long; segment IX ending in two spinous processes with an emargination in the middle. Ventral operculum on abdominal segment IX pentagonal. Abdominal hooks lacking teeth on inner margin.Body elongate, subcylindrical, parallel sided; color yellowish brown to reddish brown; tegument surface with several spatulate and scale-like setae as long as antennae (excluding sensorium), especially on head, sternal region of thorax, legs and first abdominal sternite Figs.\u00a0\u20135. Head Elongate, cylindrical, sides subparallel, thorax slightly wider than abdomen Fig.\u00a0. Color yCapable of retraction into the thorax. Head capsule subquadrangular Fig.\u00a0 ; 8\u00b01\u203226.29\u2033N, 76\u00b04\u203253.18\u2033W; 225\u2009m a.s.l.; 24 oct. 2014; J. Garc\u00e9s leg; MUSENUV \u2022 2 specimens; the same information except (E2); 8\u00b01\u203249.21\u2033N, 76\u00b05\u203211.30\u2033W; 204\u2009m a.s.l.; MUSENUV \u2022 1\u2640; La Guajira; Cerrej\u00f3n; 21 jun. 1981; Surber ned; IAvH-Code 140959 \u2022 1\u2640, 1\u2640; Magdalena; Aracataca; Tucurinca; Tucurinca river; 10\u00b041\u203216.3\u2033N, 74\u00b01\u203229.3\u2033W; 500\u2009m a.s.l.; 8 may. 2010; C. Tamaris; T. Sierra; G. R\u00faa legs; gravel; MUSENUV.Stenhelmoides were collected within rocky substrates and leafy litter situated in streams between 30 and 682 meters above sea level (m a.s.l.). The studied streams are located in three main natural geographic Colombian regions: the Pacific (two sites), the Caribbean (four sites), and the Andean portion along the foothill of the Amazon region (three sites) Figs.\u00a0.Figure 630.The Pacific region is located in the western portion of Colombia. The streams within this region belong to the macro-basins of the Atrato and Dagua rivers in the Choco Biogeographic ecoregion. This zone is recognized for its high biodiversity and profuse endemism. The predominant life zones are the tropical rain forest (bp-T) and the very humid tropical forest (bmh-T). In addition, this zone has an extensive hydric network due to intense rainfall, with some places reporting a multi-year average precipitation as high as 10,000 mmStenhelmoides were collected in this region, with sampling sites located in the foothills of different fronts of the Sierra Nevada de Santa Marta (SNSM) and in lowlands of the Valley of the Sin\u00fa River. The SNSM offers a rich hydric network with streams characterized by short lengths and significant altitudinal gradients due to the steep slopes and confined basins in the area. The predominant vegetation is associated with the humid subtropical forest (bh-BT), mostly present in forests along poorly preserved riverbanks. The deforestation in the zone has been favored to promote agricultural activities, which has generated great pressure on the hydrographic basins31.The Caribbean region is located in the northern portion of Colombia and South America. The largest number of larvae and adults of 32.The Andean-Amazonian transition is located in the southern portion of Colombia and the collection sites correspond to the Department of Caquet\u00e1. The foothills of this mountain range have the sub-Andean forest as the primary vegetation class, which gradually merges with the upper layer of the high-Andean forest and the lower layer of the humid forest of warm floors. These ecosystems have special ecological conditions associated with the transitional environment between the fauna of Andean origin and the fauna of the Amazon plains. Despite having their own characteristics, the vegetation layers gradually mix due to the changes in the altitudinal gradients. The sub-Andean forest has been fragmented over the last decades and has been affected by agricultural activities, which has resulted in the loss of large areas of forest and the deterioration of the quality of the water bodies3.sec\u22121, and with abundant areas of rapids and rocky beds. Other six sites are located in rivers with medium- to high-order magnitude flow rates. Specifically, the Tutunendo river is the water body with the highest flow rate in the study, reporting a medium 157.67 m3.sec\u22121, a minimum 57.58 m3.sec\u22121, and a maximum 257.58 m3.sec\u22121 monthly multi-year average flows. In addition, the Hacha river reported a medium 34.5 m3/sec, a minimum 19.33 m3.sec\u22121, and a maximum 156.92 m3.sec\u22121 monthly multi-year average flows, while the Rancheria river reported a medium 6.17 m3/sec, a minimum 3.24 m3.sec\u22121, and a maximum 35.71 m3.sec\u22121 monthly multi-year average flows33. Out of this group, the Tucurinca and Torib\u00edo rivers in the Sierra Nevada de Santa Marta are the water bodies with the lowest flow rate in the study, with point measurements between 1.5 to 2.1 m3.sec\u22121 at the sampling locations in the middle basins. The Paraiso river has no information available for the flow. These creeks and rivers belong to multiple hydrographic regions in Colombia that drain to the Atlantic and Pacific Oceans and the Amazon River macro-basin.The sampling events were carried out in a heterogeneous group of water currents with different flow rates Fig.\u00a0. Three o34 which correspond to a good environmental quality category. The oxygen saturation levels between 87% and 100%, along with biochemical oxygen demands between 0.5 and 1.5\u2009mg.LO2\u22121, indicate that organic contamination in the streams is low. The pH values between 6.8 and 7.9 units indicate the presence of a stable acid-buffer system, while the specific conductance levels between 25 and 140 \u03bc.cm\u22121, reveal low mineralization of the waters in the studied streams35 . Although the distribution and substrates of larvae and adults were similar for the specimens collected as part of this investigation, both stages do not seem to share the same microhabitat.In general, the sampled streams had relatively clear fresh waters (19 to 22\u2009\u00b0C), with dissolved oxygen levels close to saturation and with low residual organic loads. The perimeter areas of the riparian corridors exhibited a different type and magnitude of vegetation coverage, with a secondary forest condition in a relatively good conservation state. For those streams with available information, the water quality index values fluctuated between 50 and 74 units (ICA-FSN)Stenhelmoides was found co-occurring with larvae and adults of Austrolimnius formosus , Cylloepus Erichson, 1847, Disersus Sharp, 1882, Heterelmis Sharp, 1882, Hexanchorus Sharp, 1882, Huleechius Brown, 1981, Macrelmis Motschulsky, 1860, Microcylloepus Hinton, 1935, Neocylloepus chaparensis Manzo & Moya, 2010, Neoelmis Musgrave, 1935, Phanocerus congener Grouvelle, 1898, Pharceonus volcanus Spangler & Santiago-Fragoso, 1992 and Xenelmis Hinton, 1936.In this study, et al. diagnosed and illustrated \u201cElmidae larva D\u201d in figures 19a and 19b as probably belonging to the genus Stenhelmoides36. That description matches with larvae described herein in the following: body elongated and cylindrical; integument covered by thick setae; head without frontal tooth; procoxal cavities open; pronotal disc without tubercles; pro- meso- and meta- thoracic pleural sclerites divided into two parts; pleural sclerites only on abdominal segment I; apex of abdominal segment IX with a pair of spinous processes and a emargination in the middle.Passos S. rufulus is the first one described for the genus, no other species of genus could be compared; therefore, it is compared with larvae of other genera that feature some of the same diagnostics characters.Since the larva of Stenhelmoides share the presence of a very long antennal sensorium on the second antennomere with the larvae of Austrolimnius Carter & Zeck, 1929. However, Stenhelmoides is different because it has a cylindrical body with uniform tuberculation, pleural sclerites defined only on first abdominal segment by compete sutures, sternopleural and tergopleural sutures incomplete on second abdominal segment, ninth abdominal segment with large spinous processes, presence of spatulate and scale-like setae on head and thorax and stemmata reduced.Larvae of Stenhelmoides larvae are also similar to those of Cylloepus and Huleechius in body shape and tegument; however, they are easily distinguished because they have a long antennal sensorium, frontal teeth absent, only one pair of pleurites on first abdominal segment and a pair spinous processes on the last abdominal segment with an emargination in the middle.Typhloelmis Barr, 2015 appear to be the most similar to those of Stenhelmoides. Both genera share a cylindrical body form, stemmata absent, antennal sensorium very long, large membranous areas between the thoracic sternal sclerites, coxal cavities open, thoracic pleuron divided in two pairs of sclerites, pleural sclerites present only on the first abdominal segment, and tip of the ninth abdominal segment emarginated with two dorsal lateral spinous processes. Conversely, the two genera can be easily distinguished because the second abdominal segment is ring-shaped since it lacks sternopleural sutures in Typhloelmis, while the sternopleural sutures extend to the second abdominal segment in Stenhelmoides. In addition, Stenhelmoides has strong translucent spatulate setae on the anterior region of head, thoracic sternum, legs and first abdominal ventrite, rather than the pale spines present in Typhloelmis. In Stenhelmoides, the setiferous tubercles of the tegument are denser than those of Typhloelmis, about 0.5\u20131 times their diameter instead of 1\u20132 times. The larvae of Stenhelmoides also have a median conical sternal process bearing stout scale-like spatulate setae, while the sternum seems to be membranous in Typhloelmis. Adults of Typhloelmis and Stenhelmoides share some similarities, such as a dorsal plastron, an oblong shape and lack of carinas in pronotum and elitra14.Larvae of Stenhelmoides and Typhloelmis14 a similarity in the microhabitat of the larva is hypothesized. Consequently, larvae of Stenhelmoides with stemmata absent (or reduced to one ocular pigment lacking lens) and body coating of strong setae, could inhabit hyporheic zones or shelters formed between the rocks.Considering the similarities between adults and larvae of 37, Stenhelmoides does not key out because there is a conflict in couplet 4. The first option is Cylloepus, with cylindrical body and sternopleural suture reaching the abdominal segment IX. The second option includes several other body shapes, except cylindrical. Stenhelmoides does not match with any option; therefore, two new couplets are proposed in order to update the key:According to the larval key of South Americaa4Body shape cylindrical.....................................................................................................................................44\u2032Body shape not cylindrical................................................................................................................................5aSternopleural sutures reaching the ninth abdominal segment; anterior region of head with a pair of prominent teeth...................................................................................................................................Cylloepus4a\u2032Sternopleural sutures reaching the second abdominal segment; anterior region of head without teeth..............................................................................................................................................Stenhelmoides438, Stenhelmoides does not key out, because there is a conflict in couplet 5. The first option includes larvae with a short antennal sensorium, while the second option is Austrolimnius with a long antennal sensorium and pleural sclerites on abdominal segments I to VII. Stenhelmoides does not match with any character, therefore to update the key two new couplets are proposed:Similarly, in the larval key of Neotropics5(4)Second antennomere sensory appendage short, 0.05 indicated non-statistical (NS) difference.The results were replicated 3 times and represented as mean \u00b1 standard deviation. All experimental data were analyzed by Student\u2019s t test. P. urinaria, P. zeylanica, and S. dulcis were parallelly carried out as a control. A. niger, A. flavus, and F. oxysporum was suppressed by the presence of AgNPs in the nanoparticle concentration dependent manner, while the pure extracts were not influenced the proliferation of the fungus under the same concentration, which demonstrated the anti-fungal activities of P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs.P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs were tested for antifungal ability against A. niger, A. flavus, and F. oxysporum on various agar dishes were followed as a function of time interval until 96 h under mild conditions. Their formation and physicochemical properties were well characterized by UV-Vis, FTIR, EDX, TEM, and SEM. The results revealed that P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs were modified with variously organic compounds in biosynthesis process. So the formation and the coating procedure of these silver nanoparticles were performed at the same time. The plant species possessing the different phytoconstituents that lead to influence on the size and morphology of silver nanoparticles. P. urinaria and P. zeylanica leaf extract could form the silver nanoparticles about 28.3 and 26.7 nm, especially S. dulcis leaf extract could create almost 5 nm particles. Among the three AgNP types, only P.zey.AgNP showed a diversified morphology including spherical, triangle, plate-like polyshaped, pentagonal, and hexagonal shapes, while the others were in spherical morphology. In addition, the antifungal ability of P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs against A. niger, A. flavus, and F. oxysporum were validated. This green method is the simplest and most largely scalable method for the production of antifungal silver nanoparticles in biomedical and agricultural applications.In the study, three kinds of silver nanoparticles were successfully biosynthesized by simply adding silver (I) ions to herbal plant extracts"} +{"text": "Gesneriaceae, the biogeography and evolution of the Asian Gesneriaceae are outlined and discussed. Most of the Asian Gesneriaceae belongs to Didymocarpoideae, except Titanotrichum was recently moved into Gesnerioideae. Most basal taxa of the Asian Gesneriaceae are found in the Indian subcontinent and Indo-China Peninsula, suggesting Didymocarpoideae might originate in these regions. Four species diversification centers were recognized, i.e. Sino-Vietnam regions, Malay Peninsula, North Borneo and Northwest Yunnan (Hengduan Mountains). The first three regions are dominated by limestone landscapes, while the Northwest Yunnan is well-known for its numerous deep gorges and high mountains. The places with at least 25% species are neoendemics (newly evolved and narrowly endemic) which were determined as evolutionary hotspots, including Hengduan Mountains, boundary areas of Yunnan-Guizhou-Guangxi in Southwest China, North Borneo, Pahang and Terengganu in Malay Peninsula, and mountainous areas in North Thailand, North Sulawesi Island. Finally, the underlying mechanisms for biogeographical patterns and species diversification of the Asian Gesneriaceae are discussed.Based on an updated taxonomy of Gesneriaceae Rich. & Juss. ex. DC. is a middle-sized family, including about 150 genera and over 3400 species and subfamily Gesnerioideae Burnett ( species . Traditiyledons) .Sanangoideae Weber , Didymocarpoideae Arn. and Gesnerioideae Burnett. In this newest classification system, the monotype genus Titanotrichum Solereder in Asia (China and Japan) has been transferred to the subfamily Gesnerioideae, which was formerly treated as \u201cNew World Gesneriaceae\u201d Y.Z. Wang (Henckelia Spreng. (Paraboea (C. B. Clarke) Ridley Ridley and the Bentham . Furtheriddleton , Chayamaiddleton , Middletiddleton , Rachuniiddleton . Such siGBIF for all the species of the Asian Gesneraiceae. The species diversity and systematic positions of all genera were determined according to the newest literatures from res e.g. . We usedGesneriaceae, we identified the Asian Gesneriaceae as belonging to three areal types and 20 subtypes as below.Based on I. PantropicsRhynchoglossum Blume.I1. Tropic Asia and tropic America disjuncted: Boea Comm. ex Lam., Cyrtandra J. R. Forster & G. Forster, Stauranthera Bentham, Rhynchotechum Blume.I2. Tropic Asia to tropic Australia: Epithema Blume.I3. Tropic Asia to tropic Africa: II. Tropical and subtropical AsiaAeschynanthus Jack, Paraboea (C. B. Clarke) Ridley, Dorcoceras Bunge, Codonoboea Ridl., Didymostigma W. T. Wang, Henckelia Spreng., Didymocarpus Wallich.II1. Widespread in tropical and subtropical Asia: Boeica C. B. Clarke, Leptoboea Benth., Beccarinda Bentham, Microchirita, Middletonia D.J. Middleton.II2. East India to Java: Tetraphyllum C.B.Clarke, Deinostigma W.T.Wang & Z.Y.Li, Damrongia Kerr ex Craib, Kaisupeea B.L. Burtt, Tribounia D.J. Middleton ex M. M\u00f6ller, Billolivia, Chayamaritia, Rachunia D.J. Middleton.II3. Indo-China Peninsula: Pseudochirita W. T. Wang, Anna Pellegrin.II4. North of Indo-China Peninsula: Primulina Hance, Whytockia W. W. Smith, Hemiboea C. B. Clarke, Glabrella M. M\u00f6ller & W. H. Chen, Gyrocheilos W. T. Wang, Raphiocarpus Chun, Petrocodon Hance, Allostigma W. T. Wang, Allocheilos W. T. Wang, Gyrogyne W. T. Wang, Litostigma Y.G. Wei, Fang Wen & M. M\u00f6ller.II5. Subtropic Asia (Southwest and South China): Ornithoboea Parish ex C. B. Clarke.II6. Malay Peninsula to Southwest China: Cathayanthe W. Y. Chun, Metapetrocosmea W. T. Wang.II7. Hainan Island: Championia Gardn., Jerdonia Wight.II8. Sri Lanka and India: Orchadocarpa Ridl., Emarhendia R. Kiew, A. Weber & B.L. Burtt, Senyumia R. Kiew, A. Weber & B.L. Burtt, Somrania D.J. Middleton, Spelaeanthus R. Kiew, A. Weber & B.L. Burtt.II9. Malay Peninsula: Agalmyla Blume, Monophyllaea R. Br., Loxocarpus R. Br., Loxonia Jack, Didissandra C.B. Clarke, Liebigia, Ridleyandra A. Weber & B.L. Burtt.II10. Malay Archipelago: Hexatheca C.B. Clarke.II11. Borneo Island: III. North TemperateOreocharis Bentham.III1. Widespread in East Asia: Corallodiscus Batalin, Loxostigma C.B. Clarke.III2. Sino-Himalaya: Conandron Sieb. & Zucc., Titanotrichum Solereder.III3. Sino-Japan: Rhabdothamnopsis Hemsl.III4. Hengduan Mountains to Yunnan Plateau: Briggsiopsis K. Y. Pan, Petrocosmea Oliver.III5. Hengduan Mountains to Central China: Platystemma Wallich.III6. Himalaya: Didymocarpoideae, harbouring 85% genus and more than 90% species of Didymocarpoideae. Indo-China Peninsula and Southwest China , i.e. Sino-Vietnam Region including boundary areas of Guizhou-Yunnan-Guangxi in Southwest China, Northwest Yunnan (Hengduan Mountains), Malay Peninsula and North Borneo Fig. . In a stTribounia, Billolivia, Chayamaritia . Boea was no longer widespread in tropic Asia and its endemic center appeared in Papua New Guinea and the Solomon Islands TribouniaGesneriaceae.We determined places where at least 25% species are local endemics as \u2018evolutionary hotspots\u2019. Six evolutionary hotspots were identified, i.e. Northwest Yunnan (Hengduan Mountains), boundary areas of Yunnan-Guizhou-Guangxi in Southwest China, mountains in North Thailand, Malay Peninsula, North Borneo, and North Sulawesi Fig. . These eGesneriaceae, similar pattern found in Begonia origin, with the Gondwana broken down and dispersed all over the world. This hypothesis is based on Gesnerioideae spreading to South America via the Antarctic and Didymocarpoideae by migrating northwards, \u2018dropping\u2019 representatives in Africa and Madagascar and finally reaching the Eurasiatic continent and spreading from there to the Malay Archipelago and the Pacific. This hypothesis, however, faces difficulties both from the geological time scale and the molecular data. Jerdonia (mountains of SW India), Corallodiscus , Tetraphyllum, Leptoboea and Boeica . Only Rhynchotechum, about 18 species, which is widespread from Himalayas to Malay Archipelago, and one other species, even reaches New Guinea. Furthermore, Boea was the only endemic genus at the east side of the Huxley\u2019s Line. Therefore, the Asian Gesneriaceae may have originated from the Indian subcontinent and/or Indo-China Peninsula, then dispersed to the east and the north and finally reached Southeast Asia and East Asia.Didymocarpoideae and Gesnerioideae probably separated at about 74 Ma between tropical America, Africa and Asia.The alternative hypothesis is that the Asian Eurasia . HoweverGesneriaceae, like Monophyllaea and a section of Streptocarpus Lindl. in the Old World. Epiphytes and non-epiphytes have the same speciation rate, but epiphytism has a much lower extinction rate (Gesneriaceae only the New World Codonanthecrassifolia was confirmed to have some CAM-like characteristics (According to ion rate . This mey birds) . In orchy birds) , but in eristics .Streptocarpus shows the evolution of growth forms, especially rosulate and unifoliate growth and they believed this was an adaptation for deep shade and unifoliate growth increasing diversification rate fruits facilitate their colonisation throughout the Southeast Asia islands and nearby Pacific islands via bird dispersals , located at the eastern fringe of the Tibetan Plateau, is widely recognised as a globally important biodiversity hotspot and the red here . Such a on route .Gesneriaceae, along with underlying mechanisms of the family\u2019s dispersal, adaptation and evolution. The family is still undergoing quick diversification and is awaiting further detailed studies not only about ecological adaptations but also evo-devo examinations on relationships between micro- and macro-evolution. Molecular biogeographic studies on the typical pantropic taxa using updated techniques such as sequenced restriction-site associated DNA (In conclusion, we have discussed the biogeographic and diversification patterns of the Asian ated DNA are also"} +{"text": "Schizothorax plagiostomus and constructed phylogenetic association tree of S. plagiostomus with 23 schizothoracine fishes. We found S. plagiostomus to be closely associated with S. labiatus, S. richardsonii, S. progastus, and S. esocinus, with high-bootstraps values. Several conserved sequence blocks were identified within D-loop sequences. These are highly conserved within genus Schizothorax compared to other. This study reports the phylogenetic position of the S. plagiostomus among schizothoracines fishes and organization of D-loop region in S. plagiostomus from Pakistan.Cytochrome B (Cyt B) gene and control region of mitochondrial DNA are considered important for evaluating phylogenetic association of a species. In this study, we sequenced Cyt B and control region of Mitochondrial DNA is haploid, maternally inherited, lack recombination and has fourfold lower effective population size, hence useful for the identification of genetic diversity and population construction gene is a molecular marker, suitable for evolutionary analysis, phylogenetic studies and relationships due to its small size and the high nucleotide substitution rate at synonymous sites , Schizopyge niger (NC_022866.1), S. progastus (NC_023366.1), S. yunnanensis (KP892531.1), S. kozlovi (NC_027670.1), S. lantsangensis (NC_026294.1), S. chongi (NC_024621.1), S. biddulphi (NC_017873.1), S. nepalensis (NC_031537.1), S. davidi (NC_026205.1), S. nukiangensis (KT223584.1), S. prenanti (NC_023829.1), S. oconnori (NC_020781.1), S. waltoni (KC513574.1), S. wangchiachii (NC_020360.1), S. macropogon (NC_020339.1), S. graham (NC_029708.1), S. lissolabiatus (NC_027162.1) S. dolichonema (KJ577589.1), Schizopyge gongshanensis (NC_031803.1), S. richardsonii (NC_021448.1), S. labiatus (KT944287.1), and S. pseudoaksaiensis (NC_024833.1).In the present study, we used Cyt B gene and D-loop region of mitochondrial DNA of 23 closely related species to evaluate the S. plagiostomus was constructed using Cyt B gene and D-loop . The S. plagiostomus of Northern Pakistan in the current studies showed close relationship with Schizothorax spp from Kashmir, India. The possible explanation may be the same origin or river interconnection in the sub-Himalayan region. Tilak (S. labiatus and S. plagiostomus, the two species that specialize in hypertrophied lip structures. These specimens even shared faster running water and even spawning grounds where introgression seems impossible. Prolonged evolution of schizothoracine has been suggested by Das and Subla (S. plagiostomus is D-loop. It is 935\u2009bp in length and found to be highly variable showing microsatellite repeats at 3\u2032 end (The phylogeny of the schizothoracines is useful for taxonomy and the investigation of evolutionary pattern of this genus in Himalayan and sub-Himalayan region. The phylogenetic position of d D-loop . The S. n et\u00a0al. , 2017 whn. Tilak identifind Subla under set 3\u2032 end . The tRNt 3\u2032 end . Severalt 3\u2032 end which art 3\u2032 end . Conservt 3\u2032 end . D-loop t 3\u2032 end . The TASt 3\u2032 end . Althougt 3\u2032 end . The CSBt 3\u2032 end .Schizothorax fishes is very complex in continent and sub-continent with fascinating relationships. In few schizothoracines species like S. plagiostomus, S. esocinus, and S. labiatus, the mitochondrial sequences are so similar to classify these separately as species. This lack of variation in schizothoranice species might be described by introgressive hybridization, rapid radiation, incomplete lineage sorting, and homoplasy (Tsigenopoulos and Berredi Schizothorax species (Das and Subla S. plagiostomus with S. esocinus, S. labiatus, S. progastus, and S. richardsonii. The control region did not show any unusual sequence.Evolution of"} +{"text": "Scientific Reports 10.1038/s41598-018-35498-x, published online 28 November 2018.Correction to: The original version of this Article contained errors.The author R. Lawrence Edwards was omitted from the Supplementary Material author list and the Author Contributions Statement. The Author Contributions statement now reads:\u201cY.A.B. and J.A.W. prepared the manuscript. Y.A.B. and J.A.W. carried out \u03b418O analyses, Th/U dating and XRD analyses. F.W.C., H.C., D.S., R.L.E., and K.P.J. provided lab support. A.S., L.B., J.A.W., F.W.C and H.C. carried out the fieldwork. H.C. directed the project. E.P.D. and all authors provided comments on the manuscript and assisted with discussions.\u201dAdditionally, the following affiliation was omitted from the Supplementary Information file:\u201cDepartment of Earth Sciences, University of Minnesota, Minneapolis, MN 55455, USA.\u201dFurthermore, the Data Availability Statement has been updated from:\"After acceptance of the manuscript, the data produced here will be published in a public database such as NOAA or PANGAEA.\"to:https://www.ncdc.noaa.gov/paleo-search/study/25970)\u201d.\u201cThe data presented in this research article can be downloaded from the NOAA paleoclimate database In addition, Yassine Ait Brahim was omitted as being a corresponding author. Correspondence and request for materials can also be addressed to aitbrahim@xjtu.edu.cn.Lastly, in the original HTML version of this Article, R. Lawrence Edwards was incorrectly affiliated with \u2018Climate Geochemistry Department, Max Planck Institute for Chemistry, Mainz, Germany\u2019. The correct affiliation is listed below:\u201cDepartment of Earth Sciences, University of Minnesota, Minneapolis, MN 55455, USA.\u201dThese errors have been corrected in the HTML and PDF versions of the Article, as well as in the Supplementary Material."} +{"text": "Temporal variability in health-care processes or protocols is intrinsic to medicine. Such variability can potentially introduce dataset shifts, a data quality issue when reusing electronic health records (EHRs) for secondary purposes. Temporal data-set shifts can present as trends, as well as abrupt or seasonal changes in the statistical distributions of data over time. The latter are particularly complicated to address in multimodal and highly coded data. These changes, if not delineated, can harm population and data-driven research, such as machine learning. Given that biomedical research repositories are increasingly being populated with large sets of historical data from EHRs, there is a need for specific software methods to help delineate temporal data-set shifts to ensure reliable data reuse.EHRtemporalVariability is an open-source R package and Shiny app designed to explore and identify temporal data-set shifts. EHRtemporalVariability estimates the statistical distributions of coded and numerical data over time; projects their temporal evolution through non-parametric information geometric temporal plots; and enables the exploration of changes in variables through data temporal heat maps. We demonstrate the capability of EHRtemporalVariability to delineate data-set shifts in three impact case studies, one of which is available for reproducibility.EHRtemporalVariability enables the exploration and identification of data-set shifts, contributing to the broad examination and repurposing of large, longitudinal data sets. Our goal is to help ensure reliable data reuse for a wide range of biomedical data users. EHRtemporalVariability is designed for technical users who are programmatically utilizing the R package, as well as users who are not familiar with programming via the Shiny user interface.https://github.com/hms-dbmi/EHRtemporalVariability/Availability: https://cran.r-project.org/web/packages/EHRtemporalVariability/vignettes/EHRtemporalVariability.htmlReproducible vignette: http://ehrtemporalvariability.upv.es/Online demo: The widespread adoption of data-sharing technologies, health information standards, and open-data initiatives are inspiring the creation of research data repositories that contain large-scale historical data from electronic health records (EHRs) . These rMost recently, researchers from the machine-learning community have identified EHR data as an important source of labeled data with which diagnostic and prognostic models can by constructed . Among tTemporal variability artifacts\u2014in the form of data-set shifts\u2014can impact data quality and challenge the secondary use of data, particularly for population and data-driven research , 12\u201314, To circumvent these issues, researchers have traditionally deployed statistical process control\u2013based methods, which expose the time-points at which reference changes occur. Shewhart and Levey-Jennings charts, for example, have been employed in laboratory quality control efforts , 19. SimrEHR package focuses on querying and filtering, while the EHR and comoRbidity packages allow the performance of descriptive, Phenome-Wide Association Studies (PheWAS), and comorbidity analyses [MTS or qcc, allow the performance of time-series or statistical process control\u2013based analyses, which assist in detecting data-set shifts in EHRs [In the R programming language, there are distinct packages that can help in managing or describing EHRs. For example, the analyses . Other p in EHRs , 28.To our knowledge, EHRtemporalVariability is the first package that provides specific data-set shift delineation, which can be used on raw EHRs and other data sources. The key advantage is its suitability for multi-modal and highly coded information, which are common features of biomedical data.RRID:SCR_001905) and Shiny app (RRID:SCR_001626) with minimum effort. Data can flow through the pipeline from their initial raw, individual-level state to the final results.EHRtemporalVariability is designed to explore and identify the temporal variability of categorical and numerical data over time. The app provides the means to visually and analytically delineate data-set shifts in multi-modal and highly coded information. A key advantage is that no distributional assumptions are made. This enables straightforward use, as well as visual analytics on large EHR-coded and numerical variables with no loss of information. In addition, the tool's methodological and iterative use can identify and define reference changes that might otherwise impede further research. Analyses can proceed using both the R package trends, represented as continuously flowing time batches; (ii) abrupt changes, shown as gaps between groups of batches; (iii) temporal subgroups, depicted as clusters of batches; and (iv) seasonality, portrayed as temporal cycles. Batches are labeled by date and color-coded to distinguish seasonal effects. Additionally, IGT plots can include a smoothed trajectory of the information evolution over time. The IGT plot data also provides the means to identify those changes in order to model seasonal effects or apply clustering methods to depict temporal subgroups . ComplemOverall, the EHRtemporalVariability R package Fig.\u00a0 and ShinThe Shiny app provides a graphical user interface with two objectives. First, users unfamiliar with R programming can load .csv files and easily produce and visualize their results, which can be exported as an .Rdata file for further inspection in R. Second, we provide an exploratory, dynamic dashboard to improve the user experience, enabling a means to load results exported from the R package as an .RData file. We customized both the R package and Shiny app visualizations for users who are color-blind.A more detailed description of methods is available in the We validated the functionality of EHRtemporalVariability using 3 case studies. The first involved the i2b2 (Informatics for Integrating Biology & the Bedside) Boston Children's Hospital Autism Spectrum Disorders cohort (BCH-ASD), including 12,000 patients whose data were recorded from 1981 to 2016. This project was reviewed by the Boston Children's Institutional Review Board.2). Accordingly, we discovered an abrupt change in the relative frequencies of ICD-9-CM codes during that month. Specifically, the DTH of the ICD-9-CM codes .The second case study replicates a baseline experiment we previously performed using the mortality registry of Valencia, Spain . The reg3dhttp://ehrtemporalvariability.upv.es/ and in theGigaScience Database [Finally, we validated EHRtemporalVariability with the National Hospital Discharge Survey (NHDS)\u2014an open data set that includes 3.25\u00a0million inpatient discharges from US hospitals 2000\u20132010)\u2014and both demographic and ICD-9-CM\u2013coded data. Again, we uncovered several abrupt changes throughout multiple variables , 9, incl0\u2014and botDatabase , and a tIn light of the changes uncovered by EHRtemporalVariability, we argue that users of the package can more accurately repurpose their data analyses. For example, in the presence of abrupt changes, one can compare the performance of predictive modeling using only the most recent temporal subgroups versus full data inclusion.In addition, incremental learning approaches can also be adopted to deal with abrupt changes and continuous trends in machine learning, as can introducing seasonal or subgroup-related effects on models. Finally, in cases of descriptive analyses, such as those in PheWAS studies, we suggest evaluating the possible effects of temporal changes in results by making separate analyses at distinct temporal subgroups, as opposed to performing a more global analysis.In conclusion, EHRtemporalVariability is a data quality assessment tool that enables the broad exploration and repurposing of large data sets collected over time. We view the app as a key stepping stone toward the identification of data-set shifts for data reuse, specifically in machine learning. Target users are biomedical data scientists and bioinformaticians, as well as epidemiologists and hospital data managers. The tool can assist in exploring the effects of system, protocol, and environment-induced changes on data. We also encourage the use of EHRtemporalVariability to analyze the impact of the adoption of new coding systems, such as the ICD Tenth Revision . EHRtempProject name: EHRtemporalVariabilityhttps://github.com/hms-dbmi/EHRtemporalVariability/Project home page: Operating system(s): Platform independentProgramming language: ROther requirements: R 3.3.0, dplyr, plotly, shiny, zoo, xts, lubridate, RColorBrewer, viridis, scales, methods, MASSLicense: Apache License 2.0https://cran.r-project.org/package=EHRtemporalVariabilityCRAN repository: bio.tools ID: biotools: ehrtemporalvariabilityRRID:SCR_018663SciCrunch ID: https://github.com/hms-dbmi/EHRtemporalVariability-shinyShiny app repository: https://cran.r-project.org/web/packages/EHRtemporalVariability/vignettes/EHRtemporalVariability.htmlReproducible vignette: http://ehrtemporalvariability.upv.es/On-line Shiny app demo (for privacy reasons loading raw .csv data is disabled): https://www.cdc.gov/nchs/nhds/index.htm. A random subset of this data-set is available as a proxy for testing purposes within the EHRtemporalVariability package, and reproducible examples are available within the package help, its vignette, and the online demo . An archival snapshot of the code is available in theGigaScience GigaDB repository [The data of the National Hospital Discharge Survey case study are publicly available at pository . Access BCH-ASD: Boston Children's Hospital Autism Spectrum Disorders cohort; DTH: data temporal heat map; EHR: electronic health record; ICD: International Classification of Diseases; ICD-9-CM: ICD Ninth Revision, Clinical Modification; IGT: Information Geometric Temporal; NHDS: National Hospital Discharge Survey; PheWAS: Phenome-Wide Association StudiesThe authors declare that they have no competing interests.This work was supported by Universitat Polit\u00e8cnica de Val\u00e8ncia grant PAID-00\u201317, Generalitat Valenciana grant BEST/2018, and projects H2020-SC1\u20132016-CNECT No. 727560 and H2020-SC1-BHC-2018\u20132020 No. 825750.C.S., A.G.S., J.M.G.G. and P.A. conceived the R package. C.S., A.G.S., I.K. and P.A. conceived the BCH case study. C.S. and J.M.G.G. conceived the original methods and NHDS and Mortality case studies. C.S. programmed the R temporal variability analysis methods and plots. C.S. and A.G.S. programmed the R package wrapper, data loading and pre-processing functions, Shiny app, and wrote the documentation. C.S. and A.G.S. performed data collection, processing and analysis of the BCH case study. C.S. and J.M.G.G. performed data processing and analysis of the NHDS and Mortality case studies. C.S., A.G.S., I.K., J.M.G.G. and P.A. reviewed and interpreted the results. C.S. drafted the article. C.S. and A.G.S. drafted the figures. C.S., A.G.S., I.K., J.M.G.G. and P.A. provided critical revision of the article and approved the final version to be publishedC.S., A.G.S., J.M.G.G. and P.A. conceived the R package. C.S., A.G.S., I.K. and P.A. conceived the BCH case study. C.S. and J.M.G.G. conceived the original methods and NHDS and Mortality case studies. C.S. programmed the R temporal variability analysis methods and plots. C.S. and A.G.S. programmed the R package wrapper, data loading and pre-processing functions, Shiny app, and wrote the documentation. C.S. and A.G.S. performed data collection, processing and analysis of the BCH case study. C.S. and J.M.G.G. performed data processing and analysis of the NHDS and Mortality case studies. C.S., A.G.S., I.K., J.M.G.G. and P.A. reviewed and interpreted the results. C.S. drafted the article. C.S. and A.G.S. drafted the figures. C.S., A.G.S., I.K., J.M.G.G. and P.A. provided critical revision of the article and approved the final version to be published.giaa079_GIGA-D-19-00376_Original_SubmissionClick here for additional data file.giaa079_GIGA-D-19-00376_Revision_1Click here for additional data file.giaa079_Response_to_Reviewer_Comments_Original_SubmissionClick here for additional data file.giaa079_Reviewer_1_Report_Original_SubmissionJing Zhao -- 1/24/2020 ReviewedClick here for additional data file.giaa079_Reviewer_2_Report_Original_SubmissionEmre Guney -- 4/26/2020 ReviewedClick here for additional data file.giaa079_Reviewer_2_Report_Revision_1Emre Guney -- 6/12/2020 ReviewedClick here for additional data file.giaa079_Supplemental_FilesClick here for additional data file."} +{"text": "Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu is a popular ornamental species of Magnoliaceae. In the present study, the complete chloroplast genome (cpDNA) of L. coco was sequenced, assembled, and analyzed. The results indicated that the size of chloroplast genome of L. coco is 159,828\u2009bp, which exhibits a typical quadripartite structure including a large single-copy (LSC) region of 87,958\u2009bp and a small single-copy (SSC) region of 18,768\u2009bp separated by a pair of identical inverted repeat regions (IRs) of 26,551\u2009bp each. The genome contained 131 genes (113 unique), including 86 protein-coding genes (80 unique), 37 tRNA genes (29 unique), and 8 rRNA genes (4 unique). Phylogenetic analysis showed that L. coco is affinal to L. odoratissima and forms a nomophyletic group with the latter and L. delavayi. Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu is a species of the genus Lirianthe Spach within the family Magnoliaceae, native to Fujian, Guangdong, Guangxi, Taiwan, Yunnan, Zhejiang of China and Vietnam. It is grown as an ornamental shrub or tree in popular and widely used in gardening N. H. Xia & C. Y. Wu is cultivated as a plant for perfume and used medicinally N. H. Xia & C. Y. Wu.Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu. The GenBank accession number is MT225530. The leaf sample of a shrub of Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu was collected from Kunming Arboretum, Yunnan Academy of Forestry & Grassland Science, Yunnan Province of China . The sheets of vouchered specimen are deposited at the herbaria of YAF and YCP. Total DNA was extracted from the collected fresh leaves using DNA Plantzol Reagent .In the study, we reported the complete sequence of chloroplast genome of Pachylarnax sinica (Y. W. Law) N. H. Xia & C. Y. Wu (JX280400) served as the reference, NOVO Plasty software N. H. Xia & C. Y. Wu, the complete chloroplast genome sequences of other 26 species of the subfamily Magnolioideae from NCBI were aligned using MAFFT v. 7 (Sima and Lu Liriodendron chinense (Hemsley) Sargent (KU170538) and Liriodendron tulipifera Linnaeus (DQB99947) were served as the outgroup. The maximum likelihood (ML) tree was reconstructed with RAxML to construct the shotgun library. About 1.5\u2009G pair-end (150\u2009bp) raw sequence data were obtained and the low-quality sequences were filtered through CLC Genomics Workbench v8.0 to get high-quality clean reads. Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu is 159,828\u2009bp, which exhibits a typical characteristics in its general structure with a large single-copy (LSC) region of 87,958\u2009bp and a small single-copy (SSC) region of 18,768\u2009bp separated by a pair of identical inverted repeat regions (IRs) of 26,551\u2009bp each. A total of 113 genes were successfully annotated containing 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The result of phylogenetic analysis showed that Lirianthe coco (Loureiro) N. H. Xia & C. Y. Wu is affinal to Lirianthe odoratissima (Y. W. Law & R. Z. Zhou) N. H. Xia & C. Y. Wu (MH795108) and formed a nomophyletic group with the latter and Lirianthe delavayi (Franchet) N. H. Xia & C. Y. Wu , and thia and Lu . The stu"} +{"text": "Triatoma rosai sp. nov., a new species of Argentinian Chagas disease vector. Significant morphological and morphometric differences, associated with phylogenetic support and high mortality rate of the hybrids made it possible to confirm the specific status of T. rosai sp. nov., emphasizing the importance of integrative analyses for the taxonomy of triatomines.Although all triatomines are potential vectors of Chagas' disease, there are species with greater or lesser vectorial importance. Therefore, the correct identification of triatomines species is essential for the vector control programs. In general, triatomines are identified by external morphological characters. However, some species are very similar or even morphologically identical, being important the use of complementary analyses for the correct identification of species. For this reason, this study focused on the use of morphological, morphometric, molecular data, and experimental crosses to describe Triatoma is described based on specimens collected in the Department San Miguel, Province of Corrientes, Argentina. Triatoma rosai sp. nov. is closely related to T. sordida , and was characterized based on integrative taxonomy using morphological, morphometric, molecular data, and experimental crosses. These analyses, combined with data from the literature confirm the specific status of T. rosai sp. nov. Natural Trypanosoma cruzi infection, coupled with its presence mostly in peridomestic habitats, indicates that this species can be considered as an important Chagas disease vector from Argentina.Chagas disease is the most prevalent neglected tropical disease in the Americas and makes an important contribution to morbidity and mortality rates in countries where it is endemic since 30 to 40% of patients develop cardiac diseases, gastrointestinal disorders, or both. In this paper, a new species of the genus Trypanosoma cruzi (etiologic agent of Chagas disease) , one of the world\u2019s top authority on triatomine morphology, who has contributed for more than 30 years with taxonomic and systematic studies of these vectors.T. rosai sp. nov. as an independent lineage of T. sordida sensu stricto and T. sordida La Paz, as well as T. garciabesi and T. guasayana, and related it as a sister taxon to T. sordida (The crosses between barrier) . Howeverbarrier) .Triatoma sordida A,B.Conorhinus sordidus St\u00e5l, 1859,Triatoma sordida Chagas, 1912Eutriatoma sordida Pinto, 1931Triatoma sordida Lent and Wygodzinsky 1979Conorhinus sordidus St\u00e5l, 1859 and Eutriatoma Sordida Pinto, 1931 and T. sordida sensu stricto .The cytogenetic characterization of a et al. ,18 and Ba et al. (termed T. rosai sp. nov. (termed as T. sordida Argentina) was characterized by Panzera et al. .The electrophoretic profile of a et al. . The autT. sordida from Brazil and T. rosai sp. nov. (termed as T. sordida from Argentina) since the specimens from Argentina were closer to T. matogrossensis Leite and Barbosa, 1953 than to T. sordida from Brazil. Posteriorly, the phylogenetic analyses performed by Panzera et al. [T. rosai sp. nov. (termed as T. sordida Argentina) constituted a monophyletic clade with 88% bootstrap. The authors also observed a genetic distance between T. rosai sp. nov. and T. sordida sensu stricto of 5.3%. Belintani et al. [T. sordida populations were separated into two well-defined strains: T. sordida (Bolivia and Brazil) and T. rosai sp. nov. (termed as T. sordida Argentina). This division is corroborated by phylogenetic reconstruction, species delimitations based on Poisson Tree Process (PTP), and values of genetic distances. Finally, Madeira et al. [T. rosai sp. nov. (termed as T. sordida from Argentina) and T. sordida sensu stricto from different locations in Brazil .Garcia et al. , using ma et al. with thei et al. performea et al. , throughT. rosai sp. nov. (termed as T. sordida of Argentina) and T. sordida sensu stricto performed by Calder\u00f3n-Fern\u00e1ndez and Ju\u00e1rez [The cuticular hydrocarbons analyses of d Ju\u00e1rez compriseT. rosai sp. nov. (termed as T. sordida Argentina) and T. sordida sensu stricto by Nattero et al. [T. rosai sp. nov. and T. sordida sensu stricto [Morphometric analyses of the head, wings, and thorax performed in o et al. demonstr stricto .T. rosai sp. nov. (termed as T. sordida from Argentina) has an average development time of all nymph stages of approximately 303 days, while T. sordida sensu stricto has an average time of nymph development of approximately 170 days [. rosai sp. nov. is completed in about 10 months, unlike T. sordida sensu stricto that completes its cycle in just five months [According to Oscherov et al. , T. rosa170 days . Oschero170 days also repe months .T. rosai sp. nov. (termed as T. sordida Argentina) is present in Argentina, Bolivia, and Paraguay, and T. sordida sensu stricto is present in Brazil, Bolivia, and Paraguay. Although species may overlap in Bolivia and Paraguay, there are no reports of T. rosai sp. nov. in Brazil, as well as T. sordida sensu stricto in Argentina [T. guasayana and T. patagonica have an evolutionary relationship with the T. rubrovaria subcomplex [bcomplex ,76. Sevesordida) ,77,78. Gbcomplex ,76.T. rosai sp. nov., there are 16 species reported in Argentina: P. coreodes Bergroth, 1911, P. geniculatus , P. guentheri Berg, 1879, P. megistus, P. rufotuberculatus , T. breyeri Del Ponte, 1929, T. delpontei Roma\u00f1a and Abalos, 1947, T. eratyrusiformis Del Ponte, 1929, T. garciabesi, T. guasayana, T. infestans , T. limai Del Ponte, 1929, T. patagonica, T. platensis Neiva, 1913, T. rubrofasciata and T. rubrovaria [T. garciabesi shows great morphological similarity with T. sordida (which even led to a synonymization event) [T.guasayana and T. sordida and the fact that the geographic distribution of both species overlaps in northern Argentina [T. rosai sp. nov. is a distinct species.In addition to d, 1843) . Taking De Geer, 73 and T.De Geer, 73 and T.T. rosai sp. nov. (termed as T. sordida Argentina) differs from T. sordida (T. sordida sensu stricto and T. sordida La Paz) [T. rosai sp. nov. an independent strain of T. sordida. The last two species of Triatoma described were also based on integrative taxonomy, which provides greater reliability of the specific status of these new taxa [Several phylogenetic studies showed that La Paz) ,47,48,49 La Paz) ,18,19,20new taxa ,80.T. rosai sp. nov. and T. sordida sensu stricto demonstrates in turn that, in addition to the physical barriers that possibly prevent the meeting of these insects in nature ,37. The America ), there America ,86,87,88Triatoma rosai sp. nov. (referred in the article as T. sordida Argentina) is a wild species, k strategist, present between dry and fallen trunks, tree holes, bromeliads, palm trees, in opossum (Didelphis spp.) houses and in dry cacti, which was found naturally infected with T. cruzi and is considered responsible for the parasite's wild cycle (mainly associated with bird nests). This species has also been reported in rural peridomestic , as well as in domiciliary areas [n nests) ,67,69,70T. rosai sp. nov. (termed as T. sordida Argentina) has a high rate of infection with T. cruzi, since 38.5% of the specimens analyzed were infected \u2013 it is believed that prawns and rodents are the reservoirs of the parasite in palm trees [T. rosai sp. nov. probably is the vector of T. cruzi genotype I (TcI) among opossums and can act as a secondary vector of the TcVI and TcV genotypes in domestic and peridomestic cycles. These data are of great epidemiological importance since the infection rate of T. rosai sp. nov. is extremely high when compared to T. sordida sensu stricto (rates ranging from 0.5% to 16.2% [A survey carried out on palm trees in the province of Corrientes, Argentina showed that lm trees . Maffey lm trees also sugto 16.2% ,90,91,92to 16.2% .T. rosai sp. nov., highlight the importance of integrative taxonomy for the description of new species of triatomines, and, above all, demonstrate the need for the attention of vector control programs in Argentina for this new species of Chagas disease vector.Based on the above, we describe"} +{"text": "Paleontologists define global extinctions on Earth as a loss of about three-quarters of plant and animalspecies over a relatively short period of time. At least five global extinctions are documented in the Phanerozoicfossil record (~500-million-year period): ~65, 200, 260, 380, and 440 million years ago. In addition, there isevidence of global extinctions in earlier periods of life on Earth \u2013 during the Late Cambrian (~500 million yearsago) and Ediacaran periods (more than 540 million years ago). There is still no common opinion on the causesof their occurrence. The current study is a systematized review of the data on recorded extinctions of complexlife forms on Earth from the moment of their occurrence during the Ediacaran period to the modern period. Thereview discusses possible causes for mass extinctions in the light of the influence of abiogenic factors, planetaryor astronomical, and the consequences of their actions. We evaluate the pros and cons of the hypothesis onthe presence of periodicity in the extinction of Phanerozoic marine biota. Strong evidence that allows us tohypothesize that additional mechanisms associated with various internal biotic factors are responsible for theemergence of extinctions in the evolution of complex life forms is discussed. Developing the idea of the internalcauses of periodicity and discontinuity in evolution, we propose our own original hypothesis, according to whichthe bistability phenomenon underlies the complex dynamics of the biota development, which is manifested inthe form of global extinctions. The bistability phenomenonarises only in ecosystems with predominant sexualreproduction. Our hypothesis suggests that even in the absence of global abiotic catastrophes, extinctions ofbiota would occur anyway. However, our hypothesis does not exclude the possibility that in different periods ofthe Earth\u2019s history the biota was subjected to powerful external influences that had a significant impact on itsfurther development, which is reflected in the Earth\u2019s fossil record. Global extinctions on Earth are defined by paleontologists asa loss of about three-quarters of the existing biodiversity in arelatively short interval of geologic time. At least five globalextinctions are documented in the Phanerozoic fossil record(~500 million years). These are the Cretaceous-Paleogeneextinction event (~65 million years ago), the Triassic-Jurassicextinction event (~200 million years ago), extinction near thePermian-Triassic boundary (~260 million years ago), the lateDevonian extinction (~380 million years ago), and extinctionnear the Ordovician-Silurian boundary (~440 millionyears ago). These five extinction events were first describedas \u201cBig Five\u201d extinctions based on the analysis of more than36 thousand kinds of marine invertebrate fossils, which werecatalogued in the D.M. Raup and J.J. Sepkoski\u2019s database. Some researchers argue that a sixthmass extinction is currently underway on our planet. Thisopinion is based on the estimates of species extinction ratesin the current period, which were found to be comparable tothose during global extinctions estimated on the basis of paleontologicaldata .In the last decade, intensive analysis of fossil material hasrevealed new examples of mass extinctions of complex lifeforms on Earth. There is evidence that during the early periodsof life on Earth \u2013 in the Late Cambrian (~500 million yearsago) and during the Ediacaran period (> 540 million yearsago) , extinctions wereglobal. Extinction during the Ediacaran period is consideredto be the first mass extinction of complex life forms on Earth. Let us consider the facts and hypothesesconcerning the causes of global extinctions.A number of abiogenic factors has been described that couldpotentially cause most of the big extinctions detected in theEarth\u2019s fossil record. This does not apply to the biodiversityloss during the late Ediacaran period , the late Cambrianperiod , and the modern period .The most well-known abiogenic factors that have been associatedwith the environmental disasters are: the struck of amassive asteroid ~65 million years ago , volcanicactivity and global warming ~200 million years ago , trappean eruptions ~260 millionyears ago , as well as the major Gondwanan glaciation andclimate cooling ~440 million years ago . These phenomena and their consequences associatedwith climate change allow us to explain, at least to a certainextent, the extinction near the Cretaceous-Paleogene boundary, the Triassic-Jurassic extinction event , the Late Permian extinction ,and the extinction near the Ordovician-Silurian boundary.However, it should be noted that the described externalinfluences during these periods are quite diverse and thereis still no single opinion on the causes of known extinctions,especially regarding the Late Devonian extinction ~380 millionyears ago.Therefore, analysis of another dataset demonstrates thelink between the extinction near the Cretaceous-Paleogeneboundary ~65 million years ago and the sea-level changescaused by movements of the tectonic plates orvolcanic activity .Some researchers explain the Triassic-Jurassic extinctionevent ~200 million years ago by significant climate warmingas a result of abnormally high concentrations of atmosphericcarbon dioxide of magmatic origin , which could be accompaniedby storms, lightning strikes and, as a result, fires.The latter could directly cause the global extinction of the terrestrialbiota . Some authors denythe link between the global biodiversity loss and changes inatmospheric carbon dioxide concentration during that period. Other scientists attribute mass extinctionto the emission of large volumes of volcanic sulphurous gas or to frequent warming and cooling ofthe climate caused by volcanic emissions of large volumes ofsulphurous gas followed by carbon dioxide emission . Recent studies confirm the great impact of volcanicactivity on the climate change at the end of the Triassic periodand provide evidence that toxic effect of volcanic emissionscan be associated with mercury \u2013 the most genotoxic elementon Earth .Biodiversity loss during the Late Permian ~260 millionyears ago, when more than 90 % of marine invertebrates became extinct, has been explained by various reasons: lowoxygen concentration in the surface layer of the ocean , including in combination with warm climate whichis harmful to shallow-water organisms ;ocean acidification associated with carbon dioxide release intothe atmosphere and the accompanying rapid global warmingand acid rain ; climatecooling, combined with aridity, hypoxia, and acid rain . Mathematical modeling of the Late Permian climatesupports the hypothesis that reduced biodiversity during thatperiod could be due to hypoxia and ocean warming . Recently, additional data in favor of the volcanichypothesis of the biotic crisis in the Late Permian period havebeen obtained .Biodiversity loss near the Ordovician-Silurian boundary~440 million years ago, when ~85 % of marine organismsbecame extinct, has been traditionally associated with theglobal cooling of the tropical ocean , which was accompaniedby a drop of the sea level and the loss of shallowhabitats .According to some researchers, such cooling was triggeredby a significant increase in cosmic dust in the inner space ofthe solar system due to the decay of the L-chondrite parentbody in the asteroid belt ~466 million years ago , while others deny the connection between theasteroid destruction and the level of biodiversity .Some researcher believe that scenario of the Ordovician-Silurian extinction was more complicated, included three iceages and the cause of the initial extinction was not the seacooling, but the ice melt from glaciers due to the presenceof a large ice cover and a relatively warm ocean during thatperiod causing sea level to rise . Thecause of the second extinction has been considered to be thedecreased oxygen concentration in water that occurred whenthe sea level was high before the glaciation peak in the LateOrdovician period . Nowadays, volcanicactivity is considered to be the cause of the second extinction.There are many different hypotheses about the cause ofthe Late Devonian extinction ~380 million years ago , which mainly affected the marine biota, especiallyin shallow water . Some researchersassociate it with climate cooling , which was provoked by the burial of a large amountof organic carbon with a subsequent decrease in atmosphericcarbon dioxide concentration , and wasaccompanied by the sea-level decrease .Others attribute the Devonian extinction to global warmingcaused by a massive release of methane gas into the atmosphere,which could be caused by volcanic activity . And others link it to the frequent climatechange from warming to cooling , whichwas accompanied by sea level fluctuations and was provoked by various processes, includingthe burial of a large amount of organic carbon and the dissociation of gas hydrates . Devonianextinction has also been associated with the spread of fires,the cause of which is considered to be the high concentrationof atmospheric oxygen together with dry climate , trap eruptions , asteroid fall, etc. It is overall recognized that causesof Devonian extinction are still not clear .It is also worth noting the potential uniqueness of bioticcrises during the late Devonian period and near the end of theTriassic period, which were associated not with an increasedextinction rate, but with a decrease in the rate of speciation.As for the remaining documented extinctions: during lateCambrian period ~499 million years ago ,near the end of the Ediacaran period > 540 million years ago, as well as the loss of biodiversityobserved in the modern period , they have not been associated with globalcatastrophes of an abiotic nature.Recently, the lack of oxygen in water is more and moreoften considered one of the main causes of global extinctionsof biota, including during the Ediacaran period , during the Late Cambrian period ,near the Ordovician-Silurian boundary ,during the late Devonian period , at the end of the Permian period ,and during the early Jurassic period . However,if during the late Permian period the lack of dissolvedoxygen is believed to be a consequence of a global warming, and during the late Ordovician period \u2013a consequence of a climate cooling , whatcould cause it during other periods of mass extinctions is notyet clear. Moreover, there is evidence that contradicts the assertion of oxygendeficiency in the late Ediacaran ocean.It is important to note that episodes of mass extinctions onthe Earth are strongly believed to be cyclical, which was firstnoted when creating the first comprehensive database on thefossil record of marine families during the Phanerozoic period. Over a timespan of 250 million years, eight largest extinction-intensitypeaks with a periodic fluctuation in marine biodiversity of~26\u201327 million years have been detected. Since then, datafrom the Sepkoski\u2019s dataset have beenintensively analyzed using various methods; some authorsreport the presence of a slightly pronounced periodicity ofextinctions of ~27 million years ,whereas data obtained by other researchers indicate a strictperiodicity of ~62\u201363 million years , which appeared over an intervalof 500 million years .Similar studies were conducted using alternative databases:Paleobiology Database (PBDB) of marine invertebrate fossils and Fossil Record 2 databases for marine and terrestrial fossils . Data were obtained both infavor of the presence of periodicity and against strictcyclicality .In the study seven peaks of mass extinctionsof marine families were identified within the past 250 millionyears with a time interval between them varying from 20 to60 million years. As for the PBDB material, the results of thestudy did not reveal any evidence in favor ofperiodic extinctions. However, other results confirmed theexistence of a fairly strict periodicity of ~62\u201363 million yearsin the occurrence of major extinction events in the Phanerozoic, which was alsoshown in the analysis of the Sepkoski\u2019s dataset . Recent studies of thePaleobiology Database confirm theextinction periodicity of ~27 million years, but limit them tothe last 200 million years. The certainty and significance of thecyclical nature of extinctions with periods of ~27 and ~62 millionyears in the last 465 million years has been demonstratedin other studies .It is necessary to add that one more cycle of marine biodiversitychange with a period of 140 \u00b1 15 million yearswas found in the analyses based on the Sepkoski\u2019s dataset, but cyclicality of global extinctionsin Phanerozoic with ~62\u201363 million years period was morestrict.Hense, based on various databases, researchers have reportedat least three cycles of mass extinctions with periods of26\u201330, 62\u201363, and ~140 million years during the Phanerozoiceon .A cycle with a period of ~27 million years was most clearlymanifested during the last 200 million years .In this regard, the question arises \u2013 is there a connectionbetween the observed periodicity in the diversity of terrestrial biota and those processes that are considered above to becauses of global extinctions? In other words, is there a periodicabiotic process that could underlie the observed periodicityin the diversity of marine or terrestrial biota or even Earth\u2019sentire biota?Here it is important to emphasize once again that extinctionsdescribed above are global, that is, they affect almost theentire Earth\u2019s biota, which means that if observed periodicitywas associated with abiotic factors, it could reflect only thoseprocesses that affect the entire planet and are cyclical. Fromthis point of view, two types of processes that have similarcharacteristics can be distinguished. The first are \u201cinsideplanetary\u201d processes, that is, they are associated with dynamicprocesses involved in plate tectonic motion that lead tocontinental drift, volcanic activity, changes in sea level, etc.The second are associated with extra-planetary influences andare a reflection of processes associated with the dynamics ofthe planet itself being a space object interacting with otherobjects of the universe.Let us consider the existing hypotheses on the relationshipbetween the periodicity of global extinctions and global catastrophes,which could be caused by such cyclical processes.Nowadays, there is a number of hypotheses regarding possibleconnection between the periodicity of extinctions onEarth and astronomical processes. For example, a model oflarge-scale fluctuations in the magnetic field of the Sun showsan impressive periodicity of 66 million years , which is very close to the periodicity of mass extinctionsof ~62\u201363 million years identified by analyzing at leasttwo databases of marine invertebrate fossils . Other hypotheseshave been proposed linking frequency of extinctions withfluctuations of extragalactic cosmic-ray intensity as a result ofvertical oscillations of the solar system about the galactic plane ; with the periodicity of the solarsystem passage through the plane of the Milky Way galaxy; andwith the periodicity of the passage of comets near Earth andthe fall of asteroids, which can form different periodicitiesdepending on the size of celestial body .However, in recent years, new findings indicate that periodicitiesassociated with solar system oscillations about thegalactic plane are statistically unreliable and could not cause the periodicity of extinctions onEarth. And, although some researchers disagree, it is generallyrecognized that there is no direct evidence of astronomicalreasons for the periodicity of biota extinctions on the planetEarth .As for the planetary processes, there is also a wide varietyof opinions. Some researchers explain changes in the fossilizedorganisms by periodic changes in sea level or connect them with the dynamics oftectonic movement of continental plates and their fragmentation. One of theassumptions regarding the fact that tectonic processes on Earthcould cause periodicity of mass extinctions has been basedon the data on the 60-million-year periodicity of seawaterSr87/ Sr86 ratio in marine sediments .Other researchers detect a definite correlation between thebiodiversity dynamics and the temperature regime on Earth and consider periodic global climatechanges to be the cause of extinctions. It can be noted herethat glacial-interglacial cycles on Earth had a periodicity of~135 million years , which is statisticallyindistinguishable from the periodicity of 140 \u00b1 15 millionyears, which was revealed based on the Sepkoski\u2019s dataset.Of interest is the volcano crater dating over the past 260million years, which demonstrates the cyclicity close to 26\u201327million years characteristic of thisparticular period of time . However, in general,volcanic activity during the last 300 million years is characterizedby weakly manifested cycles with a period of 15, 30,and 60 million years .As for the rather strict ~62\u201363 million-years mass-extinctioncycle identified by different researchers using differentdatabases of marine invertebrate fossils , the existing data on 60-million-yearperiodicity associated with the dynamic processes involved inplate tectonic motion and modeling dataon the large-scale fluctuations of the solar magnetic field, bothshow periodicity of 66 million years , butdo not allow strong connection with the periodicity of globalextinctions on Earth.Several times in the history of biological life on Earth havewe detected serious external influences such as fall of asteroidsand meteorites without subsequent extinction , as well as extinctions without abiotic catastrophes,which leads us to an assumption that internal causes of a bioticnature could underlie mass extinctions of biota, which at different periods could coincide with global catastrophes orbe provoked by them. We believe that these internal causesmay be a reflection of a complex dynamic behavior of a livingsystem, such as terrestrial or marine biota, or even the biotaof the entire Earth.The idea that fossil biodiversity on Earth is a reflection of theinternal laws of functioning of a global ecosystem, which isthe Earth\u2019s biota, has arisen more than once. Mass extinctions,which have been observed in the Earth\u2019s fossil recordover the past 500 million years and lead to intermittent andirregular evolutionary pace, represent just one aspect of thecomplex dynamic behavior of a global ecosystem. To explainthe phenomenon of punctuated evolution, S.J. Gouldand N. Eldredge have formulated the \u201ctheory of punctuatedequilibrium\u201d back in 1972 .This theory is not strict. It is based on \u201cempirical generalizations\u201dof a number of facts that have long been noticed bypaleontologists, which indicate that long periods of evolutionarystability, when species remain almost unchanged,alternate with short intervals of rapid qualitative change,which are characterized by \u201csudden\u201d extinction of old speciesand subsequently replacement by new types. The authors ofthis theory and other researchers have found quite strikingexamples in the Earth\u2019s fossil record confirming such pattern. Although the interpretation of some studies has beenquestioned , in general, presence ofsuch pattern in the evolutionary process is not denied .Previously, the idea of internal biotic causes that determinethe evolutionary dynamics was formulated as \u201cself-organizingcriticality\u201d , which reflects interactions between differentecosystems and was used to explain mass extinctions and thehypothesis of punctuated evolution. It was assumed that theseinteractions, together with spontaneous mutations and geneticvariations that are always present in populations, could lead tolarge evolutionary rearrangements called the \u201cco-evolutionaryavalanches\u201d. Recently, the concept of \u201cself-organizing criticality\u201dhas again attracted the attention of researchers . However, already in the 1990s and later , arguments against this concept havebeen expressed, which were based on the demonstration of thepossibility of mass extinctions using simple models of speciesadaptation to existing conditions and nutrition resourceswithout involvement of co-evolution and critical processes,both with and without influence of the abiotic factors .There exist other ideas on the internal biotic causes of thebiodiversity on Earth that relate the Phanerozoic biodiversityto the intensity of predation in marine communities and suggest a certain role for predators inthe formation of marine biota diversity, although no correlationbetween predators and preys were found in other studies. Other researchers, seeing a definite relationshipbetween biodiversity and the age of the oceanic crust,connect the history of the seafloor with the biodiversity levelvia the availability of food resources .In the existing models of the diversity dynamics of thePhanerozoic marine biota that has clear signs of punctuatedevolution in its development, the periodicity of extinctionswas not examined and was introduced into the models as agiven . However,discussing the modeling results, the authors noted thatthe causes of \u201cstaging\u201d should be sought in the structure ofdeveloping communities . A.V. Markov andA.V. Korotaev (2007) paid special attention to those life formsthat have an increased adaptive capacity associated with sexualreproduction. In this regard, we should pay attention to thestudies of A.M. Bush et al. (2016) who believe that diversificationof marine predators starting from the Cretaceous-Cenozoic period (~200 million years ago) can be explainedby the peculiarities of sexual reproduction during the directedtransfer of sperm. However, given that internal fertilization hasprobably developed as early as in the late Neoproterozoic Era(> 500 million years), such delayed diversification requiresan explanation .A number of theoretical studies has connected discontinuityand staging in the Earth\u2019s fossil record with the negative andpositive feedback regulatory loops that a priori exist in nature,and the combination of which leads to system instability. This property of feedbackregulatory loops has long been noted and was demonstratedin models of biological systems at various levels of their organization. However, it turned out thatthis is not the only mechanism that can cause instability in anonlinear dynamic system.No one doubts today that models of mathematical physicsare a powerful tool for understanding the deepest laws ofthe Universe. Methods of mathematical modeling do not yetplay such a role in the science of living systems. However,living systems are part of dynamic systems. They are openand non-linear at all levels of their organization, so the methodof mathematical modeling is potentially able to help identifythe laws of their functioning. And, the more global the systemis, the more fundamental and, at the same time, simple in essence,but not in content, should be the laws that determinesystem\u2019s functioning.To develop the idea of the internal causes of the discontinuityin evolution, we studied the evolution of large ecosystemsusing methods of mathematical modeling. We define largeecosystem as a group of organisms (population) of one species,which we designated as \u201ctransit\u201d species. In our models, such population mimics the biota of an ecosystem large enoughto be correlated with terrestrial or marine biota. These aretraditional logistic models of a frame type, in which the efficiencyof reproduction and mortality of organisms dependson population density. According to A.V. Markov, hypothesisthat the dynamics of the Phanerozoic marine biota calculatedby traditional methods(without amendments) adequately reflectsreal changes in biodiversity has not been unproved andremains the most convenient and reliable basis for meaningfulbiological interpretations .Evolution is described in models as process of ecosystemself-development (population of a \u201ctransit\u201d type), duringwhich there is a local increase in the adaptability of its individualsto the conditions of existence due to mutationalvariability and natural selection.Analysis of the dynamics of functioning of such modelshave showed that living systems with different reproductionmethods implement different evolutionary laws of selfdevelopment:\u201casexual\u201d ecosystems showed stasis, whereas\u201csexual\u201d ecosystems evolved cyclically . That is, it turned outthat if natural selection in a population is directed towardsincreasing the adaptability of its individuals to the conditionsof existence, then, at a certain stage of its evolution , such selection can act asdestabilizing factor.Moreover, it turned out that these same factors can explainthe peculiarities of punctuated evolution observed in the fossilrecord, such as mass extinctions and phases of rapid diversityincrease, as well as phases of stasis diversity, the causes ofwhich are still not understood .Figure 2 shows evolutionary phases of the density parameterof a \u201ctransit\u201d population using one full cycle of the parametervalue fluctuation. In the model, phases of decrease andincrease in the parameter value repeat an unlimited numberof times with approximately the same time interval. The exactduration of each phase cannot be predicted, since the oscillatorydynamics observed in the model is chaotic.One full evolutionary cycle of a \u201ctransit\u201d population iscompleted over time interval t conv. units,which in the model is ~12,000 conv. units of time . Theconcept of fractal evolution , whichis based on the similarity of laws that regulate the dynamicsof population density, variety of species, genera and higherlevels of organization of living systems at different timescales, allows to transfer these data when changing the timescale according with a level of organization of living systemswith more than a single population. It is easy to verify that ifone conv. unit of time equals 50 years, then duration of oneevolutionary cycle is close to the species lifespan estimate,and if it equals 500 years, we receive an estimate of the genuslifetime, the durations of which are ~0.5 and ~5.9 millionyears, respectively, according to . These rough estimates do not prove anything, butsuggest that time scales characteristic of dynamic processesat the level of large ecosystems are one order of magnitudelarger, that is, such time scales range up to tens of millionsof years and cyclic changes in the diversity of Phanerozoicmarine biota with a period of 62\u201363 million years may represent their reflection .Thus, the modeling results have shown that if the efficiencyof reproduction and mortality in a population depends on itsdensity and the most adapted individuals, the genetic diversityof which is a result of genome replication errors duringself-reproduction, are being selected, then these conditionsare sufficient for the formation of cyclical intermittent dynamicsof biodiversity in a living system with sexual type ofreproduction.The question arises \u2013 what is the origin of cyclicality andintermittency observed in the evolution of life on Earth?The idea that the phenomenon of punctuated evolution canbe based on the bistability in biological systems has beenexpressed by V.A. Likhoshvai long ago in the work dedicatedto the modeling of the evolution of a simple self-developingliving system. It was expressed as an idea of a latent phenotypein a self-developing living system, which represents aninternal resource of its evolutionary development . Subsequently, when applied to globalecosystems, this idea was transformed into the hypothesis ofthe two \u201ctrees of life\u201d.Here it should be noted that Ch. Darwin defined the diversityof living things on Earth as the \u201ctree of life\u201d. Such comparisonvery accurately reflects the deepest essence of life, whichconstantly gives rise to new thin branches of species duringits continuous evolutionary development that can eventuallyform into new genera, types, classes, etc., but can also dry outand disappear .The most common characteristics of the \u201ctree of life\u201d arebiota density and species diversity. These characteristics arereflected in our model as the population density of a \u201ctransit\u201dspecies, which at each moment in time depends on the ratiobetween the rates of self-reproduction and mortality of itsindividuals. Analysis of the behaviour of functions that dedescribechanges in these parameters at different time momentsdepending on the density of a \u201ctransit\u201d population have shownthat evolving ecosystems with asexual type of reproductionhave only one stable state, while for ecosystems with sexualtype of reproduction the bistability is possible, that is, twostable stationary states, each of which can be interpreted asthe \u201ctree of life\u201d, one of which is being manifested and theother is not. Moreover, if evolution is directed towards improvingthe adaptability of individuals of a \u201ctransit\u201d speciesto habitat conditions, which should be accompanied by nicheexpansion and increased utilization of resources, then at somepoint in time the stability of the manifested state becomeslost and the system jumps into a new steady state that existedbefore, but was unmanifested. The result of such transitioncan be interpreted as sudden \u201cdisappearance\u201d of old speciesfollowed by explosive appearance of new types, that is, thechange of one \u201ctree of life\u201d to another. From a mathematicalpoint of view, such event is not unusual in dynamic nonlinearsystems. Figure 3 demonstrates the mechanism of local andglobal extinctions depending on the rates of change of functionsdescribing self-reproduction C (red curve) and mortalityD (blue curve) of individuals of a \u201ctransit\u201d population atdifferent moments of its evolution.The intersection of functions C and D corresponds to thestationary states of the system, which can be stable (xmin andxmax) or unstable (xmdl). If current value of density and biodiversityof biota \u0445(t) is located near the stable stationary state,it falls into the region of its attraction and will tend to eitherxmax or xmin . The fact that atthe same time moment there is one more stable stationary statedoes not affect the state of the system, since x(t) value fallsoutside the region of its attraction and the system cannot getinto it without external influence. Therefore, we can assumethat at the time moment described in Fig. 3, c, stationary statexmin is manifested and stationary state xmax is not. In Fig. 3,a, d, e, on the contrary, stationary state xmax is manifested,whereas stationary state xmin is not.Since the system evolves over time towards biota sizeand diversity increase, value of the x(t) parameter increases,while the attraction region of the manifested stationary statedecreases and approaches the stationary state xmdl, so that atsome point they merge and disappear. At this time moment weobserve only one stationary state in the system \u2013 either xmin or xmax , which passes from theunmanifested state to the manifested one. Since at this timemoment the x(t) value is significantly different from the valueof the manifested stationary state , an explosivechange in the x(t) value is observed. We believe that a rapidchange in system parameters during the transition from onestate to another can be a reflection of the uneven evolutionaryrates observed in phylogenetic studies .It also follows from these data that local extinctions (blueoutline) are associated with fluctuations in the current densityand diversity of biota \u0445(t) in the attraction region of the stablestationary state xmax , while global extinctionsare associated with the loss of stationary state stability and the\u0445(t) transition to the attraction region of the stationary statexmin, which at this time moment becomes single, similar tothat shown in Fig. 3, b. It is this transition that we interpretas the change of one \u201ctree of life\u201d to another.Thus, we came to the conclusion that adaptation of organismsto the habitat conditions as a result of gradual accumulationof mutations (the evolution) may by itself be one of thecauses of instability in a living system, which manifested itselfas periodically occurring mass extinctions of biota. However,this instability manifested itself only at a certain stage ofthe evolution of living systems and was associated with thedevelopment of sexual dimorphism. This does not contradictwith the fact that during certain periods of life on Earth massextinctions could coincide with planetary environmentaldisasters or be provoked by them.Analysis of the causes of global extinctions in the Earth\u2019shistory have shown that, although abiogenic factors arerecognized as prevailing and their various combinations canexplain most mass extinctions described in the Earth\u2019s fossilrecord, they do not explain such aspects of the evolutionaryprocess as periodic discontinuity and uneven evolution oflivingorganisms. However, these are evolutionary characteristicsthat are manifested at all known levels of organizationof living systems \u2013 from molecular level to biosphere as awhole. It has now been proven that \u201cspasmodicity\u201d of evolutionat the paleontological level is reflected on the molecularlevel .We believe that in addition to external factors, there areother, internal, reasons for the occurrence of global extinctionsof terrestrial biota. According to our hypothesis, theseinternal factors are associated with the phenomenon ofbistability, which occurs only in ecosystems with prevalentsexual reproduction. The fossil record of life on Earth overthe past 500 million years reflects the life history of just suchorganisms. Our hypothesis suggests that even with no globalcatastrophes of an abiotic nature, extinctions in the evolution of living organisms would happen anyway. The possibility ofthis is evidenced by the existence of extinctions that are notyet associated with global catastrophes of an abiotic nature,as well as the evidence of serious external influences thatwere not accompanied by extinctions .We believe that the bistability phenomenon should be manifestedin the evolution of a living system at all levels ofits organization. And at least at the cellular level, we havedemonstrated the contribution of bistability phenomenon tothe evolution of cellular complexity . Thereis no doubt that at the level of the entire Earth\u2019s biota thebistability phenomenon should interfere with the abiogenicfactors observed in the fossil record of life on Earth. This isevidenced by the extinction cycle with a period of ~140 millionyears, although it was dimly manifested , which can be associated with the frequency of glaciationspreceding extinctions ; as well asby the extinction cycle with a period close to 26\u201327 millionyears, which was manifested during the last 250 million years and coincided with the dating of volcano craters.As for the rather strict cyclicity of marine extinctions manifestedover the last 500 million years, the period of which was~63 million years ,both the empirical data on the ~60 million-years periodicity ofthe Sr87/Sr86 ratio change in marine sediments , which indicates the possibility of cyclicityassociatedwith motion of tectonic plates on Earth, as well as modelingdata on the fluctuations of the Sun\u2019s large-scale magneticfield with the periodicity of 66 million years , did not conclusively link them to the periodicity ofglobal extinctions.At this stage, the modeling results do not explain the existenceof such periodicity of extinctions. 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Adv. 2018b;4(6):eaan8983.DOI 10.1126/sciadv.aan8983.Zhu Z., Liu Y., Kuang H., Benton M.J., Newell A.J., Xu H., An W.,Ji S., Xu S., Peng N., Zhai Q. Altered fluvial patterns in North Chinaindicate rapid climate change linked to the Permian-Triassic massextinction. Sci. Rep. 2019;9(1):16818. DOI 10.1038/s41598-019-53321-z."} +{"text": "Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.Major advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10\u201312 years. These tools depend upon the de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250\u00d7 more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes . The new reference assembly is accessible in annotated form for public use.We present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a We demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species. Bos taurus) in the world, being raised primarily for meat and dairy in a diversity of climates and production schemes ) and AR \u22125 and 1.59\u00a0\u00d7\u00a010\u22124, respectively, or an order-of-magnitude improvement in accuracy. This was calculated from the number of non-matching base calls from FreeBayes [To assess the error profile of our assembly and compare it to the previous reference, UMD3.1.1 NCBI ac. The tot010761 ) as previAs a measure of the completeness of the assemblies and to define the chromosome ends, we identified centromeric and teloA key measure of improvement over the previous reference is the increase in the contiguity of the genome Fig.\u00a0. The 30 The ARS-UCD1.2 assembly annotation (AR 106) generated by NCBI was compared with the UMD3.1.1 annotation (AR 105). Approximately two-thirds of the genes (85% of protein-coding genes) are identical or nearly identical between the 2 datasets . More thThese improvements in the annotation are partly due to the availability of more and longer transcript evidence for gene prediction (Iso-Seq in particular), but it is clear that uncertainty of placement and orientation of sequence across gaps has a large impact on gene annotation. Of the 21,039 genes annotated in ARS-UCD1.2, 69 (0.3%) have gaps within introns compared to 6,949 (33%) of annotated UMD3.1.1 genes Fig.\u00a0. ConsideARS-UCD1.2 also represents an improvement in base accuracy over UMD3.1.1 that is measurable in the annotation. High rates of sequencing error can disrupt the prediction of open reading frames and lead to truncated gene models or the erroneous calling of non-coding genes or pseudogenes instead of protein-coding genes. The NCBI annotation process attempts to compensate for this problem by producing a \u201ccorrected\u201d model (with name prefixed with LOW QUALITY) containing a difference with the genome sequence, when protein alignments suggest that there is an erroneous indel in the genome. The number of such \u201ccorrected\u201d models decreased by 44% from 1,828 in UMD3.1.1/AR 105 to 1,027 in ARS-UCD1.2/AR 106.This assembly represents a 200-fold improvement in sequence continuity and a 10-fold improvement in per-base accuracy over previous cattle assemblies. The assignment of megabase-length contigs to full chromosome scaffolds provides additional certainty in gene and genetic marker positions, which will influence marker-assisted selection and basic research. The assembly was selected as the reference genome for taurine cattle by the US genomic evaluation system in December 2018 and the Accession numbers for raw sequencing reads and assemblies can be found in Table S1: Sequencing resourcesTable S2: UMCLK genetic mapTable S3: Centromeric and telomeric repeatsTable S4: RefSeq transcripts not aligning to assembliesTable S5: ARS-UCD1.2 vs UMD3.1.1 annotation comparisonFigure S1: Average centromeric repeat regions. Centromeric satellite regions identified by RepeatMasker in the ARS-UCD1.2 (ARSUCD) and UMD3.1.1 (UMD3) assemblies were merged if they overlapped by 1 bp. Histogram bars show the mean length of these regions that are within the first 500\u00a0kb of a chromosome scaffold's starting base (CHRSTART), within unplaced scaffolds (UNPLACED), or in the middle of the chromosome scaffolds (CHRSCAFF). Error bars represent the 95% confidence interval (2 standard errors from the mean) of centromere lengths in each category.Supplemental Note. UMCLK genetic mapAR: annotation release; BLASR: Basic Local Alignment with Successive Refinement; BLAST: Basic Local Alignment Search Tool; bp: base pairs; BWA: Burrows-Wheeler Aligner; cDNA: complementary DNA; dbSNP: Database of Single Nucleotide Polymorphisms; Gb: gigabase pairs; kb: kilobase pairs; Mb: megabase pairs; mRNA: mesenger RNA; NCBI: National Center for Biotechnology Information; PacBio: Pacific Biosciences; PE: paired end; RefSeq: NCBI Reference Sequence Database; RNA-seq: high-throughput short-read messenger RNA sequencing; SMRT: single-molecule real-time; SNP: single-nucleotide polymorphism; SRA: Sequence Read Archive; SV: structural variant; tRNA: transfer RNA; USDA: United States Department of Agriculture.R.H. and E.T. are employed by Pacific Biosciences; all other authors declare that they have no competing interests.https://hpc.nih.gov). Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.Sequence generation was supported by USDA/NRSP-8 Animal Genome, USDA-ARS Meat Animal Research Center, Neogen, and Zoetis. B.D.R., S.G.S., J.B.C., C.P.V.T., and G.L. were supported by USDA CRIS 8042-31000-001-00-D. J.B.C. was supported by USDA CRIS 8042-31000-002-00-D. D.M.B. and W.L. were supported in part by USDA CRIS 5090-31000-026-00-D. D.M.B. was also supported in part by USDA NIFA grant 5090-31000-026-06-I. W.M.S., T.G.M., T.P.L.S. were supported by USDA CRIS 3040-31000-100-00-D. R.D.S. and T.N.R. were supported in part by USDA NIFA 2016-68004-24827. R.D.S. was also supported in part by USDA NIFA 2013-67015-21202, 2015-67015-23183, NIH 1R01HD084353-01A1, and USDA Hatch MO-HAAS0001. J.H. and F.T.N. were supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health. J.A.H. and J.C.S. were supported by funding from the UKRI-BBSRC awards BB/M027155/1, BBS/E/I/00007035, BBS/E/I/00007038, and BBS/E/I/00007039. S.K., A.R., and A.M.P. were supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. A.R. was also supported by the Korean Visiting Scientist Training Award (KVSTA) through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (HI17C2098). This work utilized the computational resources of the NIH HPC Biowulf cluster (T.P.L.S., J.F.M., C.P.V.T., R.D.S., D.M.B., and B.D.R. conceived, initiated, and managed the project. T.P.L.S. and J.F.M. were responsible for DNA and RNA sequence data production. B.D.R., D.M.B., R.D.S., S.J.S., C.D., A.Z., R.H., J.G., A.R., S.K., and A.M.P. performed assembly and associated tasks. T.N.R., W.Y.L., C.C., W.L., S.D.M., B.M.M., W.M.S., J.A.H., J.C.S., W.N., S.G.S., J.B.C., G.L., and C.P.V.T. performed quality control and/or contributed additional analyses. C.G.E., T.G.M., and E.T. performed RNA analyses. F.T.N. and J.H. performed annotation and managed public presentation of the assembly files. All authors read and edited the manuscript.giaa021_GIGA-D-19-00331_Original_SubmissionClick here for additional data file.giaa021_GIGA-D-19-00331_Revision_1Click here for additional data file.giaa021_Response-to-Reviewer_Comments_Original_SubmissionClick here for additional data file.giaa021_Reviewer_1_Report_Original_SubmissionPaul Stothard -- 10/7/2019 ReviewedClick here for additional data file.giaa021_Reviewer_2_Report_Original_SubmissionAlan Archibald -- 10/22/2019 ReviewedClick here for additional data file.giaa021_Supplemental_DataClick here for additional data file."} +{"text": "Microbial culture collections are very important components of biological science. They provide researcherswith material for studies and preserve biological resources. One such collection is the Collection of RhizosphereMicroorganisms, kept at the Institute of Biochemistry and Physiology of Plants and Microorganisms ofthe Russian Academy of Sciences, Saratov (IBPPM). Its activity is primarily directed toward the isolation and preservationof microorganisms from the plant root zone. The international research interest in microorganisms fromthis ecological niche is not waning, because they are very important for plant growth and development and, consequently,for plant breeding. The group of bacteria with properties of significance for plants has been given thename \u201cplant-growth-promoting rhizobacteria\u201d (PGPR). This group includes nitrogen-fixing soil alpha-proteobacteriaof the genus Azospirillum, which form the core of the IBPPM collection. First discovered by Brazilian scientistsin the 1970s, azospirilla are now a universally recognized model object for studying the molecular mechanismsunderlying plant-bacterium interactions. The broad range of useful properties found in these microorganisms,including the fixation of atmospheric nitrogen, production of phytohormones, solubilization of phosphates, controlof pathogens, and formation of induced systemic resistance in the colonized plants, make these bacteria anall-purpose tool that has been used for several decades in basic and applied research. This article reviews thecurrent state of Azospirillum research, with emphasis on the results obtained at the IBPPM. Scientific expeditionsacross the Saratov region undertaken by IBPPM microbiologists in the early 1980s formed the basis for the uniquecollection of members of this bacterial taxon. Currently, the collection has more than 160 Azospirillum strains andis one of the largest collections in Europe. The research conducted at the IBPPM is centered mostly on the Azospirillumstructures involved in associative symbiosis with plants, primarily extracellular polysaccharide-containingcomplexes and lectins. The development of immunochemical methods contributed much to our understandingof the overall organization of the surface of rhizosphere bacteria. The extensive studies of the Azospirillum genomelargely deepened our understanding of the role of the aforesaid bacterial structures, motility, and biofilms in thecolonization of host plant roots. Of interest are also applied studies focusing on agricultural and environmentaltechnologies and on the \u201cgreen\u201d synthesis of Au, Ag, and Se nanoparticles. The Collection of Rhizosphere Microorganismscontinues to grow, being continually supplemented with newly isolated strains. The data presented inthis article show the great importance of specialized microbial culture repositories, such as the IBPPM collection,for the development and maintenance of the microbial research base and for the effective solution of basic andapplied tasks in microbiology. Untilrecently, a very large number of Russian collections wereon the verge of ceasing their activities owing to the lack offunding. In recent years, with the approval of the Plan for theDevelopment of Biotechnologies and Genetic Engineering,an attempt was made to provide targeted organizational andfinancial support to intensely working collections.The conservation and development of biological collectionsin the Russian Federation is part of the interdepartmental andinterdisciplinary priority problem of preserving biologicalresources and biodiversity, as well as the national biologicaland food security building. The solution of this problem is thebasis for the sustainable development of Russian science asa whole, modern science-intensive industries, and training ofqualified personnel . The currently existing collections (according to theWorld Federation for Culture Collections (WFCC), there are715 of them (http://www.genetika.ru/vkpm). Several large Russian collections may claim theBRC status. Most of the collections existing as specializedunits at scientific and educational organizations cannot meetthe criteria of such large structures, but they deserve attentionas well. As a rule, they possess both a significant panelof cultures and the most complete information about them,which is their significant advantage. One such specialized unitis the IBPPM Collection of Rhizospheric Microorganisms(CRM IBPPM).The above Plan includes the foundation of large bioresourcecenters (BRCs), which will be the most important elementfor the development of biotechnology in Russia , and integration into the European andglobal information networks of biological resources. It shouldbe noted that there are already many BRCs in the world, whichare represented by both departmental and private non-profitorganizations. One such BRC was established in 2014 on thebasis of a leading Russian collection , designed to becomethe basis of the infrastructure in the field of microbial geneticresources for biotechnological purposes necessary forsupporting research in living systems ,founded in Saratov in 1980, was focused on the tasks ofincreasing crop yields in the Volga region. One of them wasthe justification of the possibility of using microbial fertilizersand, in this regard, the clarification of the role of associativenitrogen-fixing microorganisms in the nitrogen nutrition ofcrops. To solve this problem, the diazotrophic bacteriumAzospirillum was chosen as a model research object, publicationsabout which had appeared shortly before . The Institute\u2019s microbiologists mastered the methods of isolationand identification of these microorganisms andworked out methods for their conservation. In the course ofexpeditions in the Saratov region, undertaken to obtain a representativecollection of Azospirillum strains associated withwild and cultivated cereals , the investigators laid the foundation for a unique setof members of the studied bacterial taxon ,becoming part of the IBPPM Collection of Non-PathogenicMicroorganisms.The key characteristics of azospirilla in the first stages ofisolation were: colony growth on a medium with Congo red and on potato agar , aswell as microscopy and Gram staining. Because the main featuresof the isolated bacteria were the fixation of atmosphericnitrogen and the promotion of plant growth, the isolates werescreened for nitrogenase and IAA-producing activities.Taxonomic studies were carried out with original strainsof azospirilla. In addition to interspecific differentiation bymethods based on DNA\u2013DNA hybridization, intraspecificdifferences were evaluated with two variants of genomicfingerprinting: RFLP and AFLP . The plasmid composition of thestrains was studied . The obtainedisolates were screened for restriction endonuclease activity. Storage methods were being optimizedfor four years. Long-term observations showed thatAzospirillum strains frozen in liquid nitrogen retained highviability and basic differential properties at \u201370 \u00b0C.http://ckp-rf.ru). It is a specialized scientific collectionfocused on the gathering and maintenance of nonpathogenicbacteria isolated mainly from the root zone ofplants. It is a member of the WFCC with the number 975 andis registered at the World Data Center for Microorganisms(WDCM), No. 1021.In 2014, the Collection of Non-Pathogenic Microorganismswas transformed into the CRM IBPPM includes about 500 cultures of rhizospheric bacteria belongingto 28 genera: Acidovorax, Aeromonas, Alcaligenes,Aquaspirillum, Arthrobacter, Azospirillum, Bacillus, Bradyrhizobium,Brevundimonas, Comamonas, Ensifer (Sinorhizobium),Enterobacter, Herbaspirillum, Kocuria, Micrococcus,Moraxella, Mycobacterium, Nitrospirillum, Niveispirillum,Nocardioides, Ochrobactrum, Paenibacillus, Pectobacterium,Pseudomonas, Rhizobium, Rhodococcus, Stenotrophomonas,and Xanthomonas. Among them are bacteria isolated fromthe rhizosphere and rhizoplane of various wild and cultivatedplants, endophyte strains, strains associated with aquatic plants(macrophytes), etc.Members of the genus Azospirillum constitute approximatelyhalf of the collection. In addition to the original strainsisolated in the Saratov region, the collection includes azospirillaof various geographical origins provided by researchers or otherculture collections. In addition, almost all the type strains ofknown Azospirillum species available in public depositoriesare maintained. Among the collection strains, there may bemembers of new species of this genus .Thus, the Azospirillum set in the CRM IBPPM is highlyrepresentative. For comparison, in DSMZ , the total bacterial stock of the genus Azospirillum is representedby 27 strains, of which 6 are type strains; at BCCM/LMG , 37 and 10; at JCM , 13 and 5; in ATCC, 14 and 3, respectively.This microorganism was first isolated by Beijerinck in 1923and described as a \u201cnitrogen-fixing Spirillum\u201d, but the researcherwas unable to confirm its ability to fix nitrogen inpure culture and called this microorganism Spirillum lipoferum. The genus Azospirillum was rediscoveredand described by Tarrand et al. (1978) but became widelyknown thanks to the scientific enthusiasm and competenceof Johanna D\u00f6bereiner, who made a significant contributionto the basic and applied research on azospirilla .The taxonomy of the genus Azospirillum, belonging to thefamily Rhodospirillaceae of the order Rhodospirillales in the class \u03b1-Proteobacteria, is developing fast. From the momentthe first two species, A. lipoferum and A. brasilense, weredescribed and until the end of the secondmillennium, only four more species were discovered: A. amazonense, A. halopraeferens , A. irakense and A. largimobile. However, since 2000, 16 newspecies have been described with valid published names:A. doebereinerae , A. oryzae , A. melinis , A. canadense , A. zeae , A. rugosum, A. picis , A. thiophilum, A. formosense ,A. humicireducens , A. fermentarium , A. soli , A. agricola , A. ramasamyi , A. griseum, and A. palustre .In 2014, Azospirillum irakense was reclassified as Niveispirillumirakense comb. nov. and Azospirillum amazonense,as Nitrospirillum amazonense gen. nov., sp. nov. . Thus, at the time of this writing, the genus Azospirillumincludes 20 species with valid published names. It is importantto note that two more species are recognized as members ofthe genus: A. palatum and A. himalayense, whose names were not validly publishedin conformity with the rules of the International Code of Nomenclatureof Bacteria.The onset of the era of genomic sequencing highlighted thedevelopment of reliable criteria for the comparative assessmentof the genomes of bacteria and archaea for taxonomy andsystematics. Recently, the first results of applying a set of phylogenetictests in the context of the development of microbegenomic taxonomy were obtained for the group of bacteriaof the genus Azospirillum whose genomes were present in theGenBank database . The author revealedthe dependence of the assessment of the taxonomic positionof strains on the type of full-genome data used related to thecore or core and variable components of the pangenome. It wasnoted that there was no unified system of assigning isolates toone or another species yet. Until the genomic databases arefilled to the necessary extent with high-quality material, theso-called \u201cpolyphase\u201d approach, based on a combination ofphenotypic, chemotaxonomic, and genotypic characteristics,remains the most correct in the taxonomy and systematics ofprokaryotes.Azospirilla, chosen as an object of research in the infancyof IBPPM, turned out to be an excellent model for studyingassociative plant-microbe interactions. Currently, Azospirillumis one of the universally recognized and widely studied plantgrowth-promoting rhizobacteria (PGPR) .Such bacteria play an important role in helping the plant adaptto external influences. In this case, a plant-microbial association(associative symbiosis) with new properties determinedby positive interactions between partners is often formed.The extreme diversity of colonizable plant species ischaracteristic of azospirilla, which indicates the multitude ofecological strategies implemented by these bacteria, as well as their wide adaptive capabilities . Bacteria adapt to theirenvironments through such abilities as fixation of atmosphericnitrogen; solubilization of phosphates; and production ofexopolysaccharides, lectins, phytohormones, siderophores,poly-\u03b2-hydroxybutyrate, etc. There is evidence that Azospirillum bacteria are involved in the formationof so-called induced systemic resistance (ISR) in partnerplants exposed to biotic stress, as well as induced systemictolerance (IST) to abiotic stress.Most Azospirillum species were isolated from the rhizosphereof land plants. So far, only three species were isolatedfrom aquatic biotopes: A. largimobile ,A. thiophilum , and A. griseum . Sequencing of the Azospirillum genome showedthat this bacterium shifted from aquatic to terrestrial existenceat the same time as vascular plants appeared on land: about400 million years ago . Almosthalf of the Azospirillum genome was acquired as a result ofhorizontal gene transfer from other terrestrial bacteria. Mosthorizontally acquired genes encode functions that are criticalto environmental adaptation.The possession of phytostimulation mechanisms makesazospirilla one of the best inoculants that are employed invarious countries to manufacture commercial biologicalproducts increasing crop yields: Azo-Green\u2122, Zea-Nit\u2122,Graminante\u2122, BioPower\u00ae, etc. .At the IBPPM RAS, the use of Azospirillum strains as modelobjects was focused mainly on the study of the structuresinvolved in the formation of associative symbiosisand/orhaving important taxonomic significance. First of all, theseare extracellular polysaccharide-containingcomplexes, whichplay very important and diverse roles in the formation and successfulfunctioning of plant\u2013microbe associations. Azospirillaproduce intricate highly aggregated compounds of polysaccharides(PSs), lipids and proteins, as well as free PSs withmolecular weights up to 20 kDa. These compounds are storedin the capsular material and released to the environment . The capsular PS-containing componentsof azospirilla are involved in the adsorption of the bacteria toplant roots. Their ability to induce deformations of root hairs ofwheat was shown for the first time .Novel information was obtained on the primary structures ofrepetitive PS units in surface lipopolysaccharides (LPSs) andcapsular PSs of more than 40 Azospirillum strains of variousorigins . In several strainsisolated from plant roots on different continents, molecularmimicry of bacterial surface glycopolymers owing to thepresence of identical or structurally similar repeating units inan O-specific PS (O-PS) was observed. It may be conjecturedthat this mimicry is associated with the implementation ofcertain strategies during the formation of associations withplants, possibly owing to the presence of several interaction mechanisms, for example, endo- and ectosymbiosis .Immunochemical methods are a good tool for the study ofbacterial surface structures. Scientists can examine structuraldetails of the main surface antigens of azospirilla to find outhow the surface of rhizosphere bacteria is generally organized.LPS is a major antigen on the surface of azospirilla;therefore, the O-PS structure determines the immunochemicalspecificity of these microorganisms .With account taken of the immunochemical characteristics ofthe carbohydrate antigens of Azospirillum bacteria, a biotestsystem for their serological identification has been developed.With the example of azospirilla, a fundamentally new typeof microbial R-S dissociation was described, owing to the redistributionof the contributions of two different (full-fledged)O-PSs to the architecture of the bacterial cell surface, dependingon the culture age . Carbohydratefragments of the glycosylated flagellin of the polar flagellumfrom A. brasilense type strain Sp7 were isolated and studied,and their chemical structures were determined . These fragments were immunochemically identicalto one of the two O-PS somatic antigens of strain Sp7.With account taken of the results obtained, which indicate theidentity of antigenic determinants in capsular PSs, exopolysaccharides,and LPSs of azospirilla, it is reasonable to suggest acommon pathway for thebiosynthesis of carbohydrate surface structures in Azospirillumbacteria.For the first time, a variant of enzyme-linked immunosorbentassay (ELISA) of microsediments of soil suspensionswas proposed that uses antibodies against Azospirillum LPSs.The assay allows the detection of the somatic bacterial antigenin soil. With the optimized ELISA variant, the dynamics ofin situ detection of the somatic antigen of A. brasilense associativebacteria introduced into soil was studied .A prominent direction in the progress of the immunochemicalmethodology at the IBPPM RAS is the study ofunique physicochemical and biochemical properties of goldnanoparticles and their bioconjugates. By using colloid goldas a carrier and an adjuvant, as well as the phage displaymethod, procedures have been developed to prepare antibodiesto various antigens and haptens . Gold and gold-silver nanoparticles were conjugatedwith antibodies to flagellin, LPS, and genus-specificsurface-protein determinants of A. brasilense type strain Sp7.Electron microscopic analysis of the A. brasilense Sp245 cellsurface involving antibodies labeled with metal nanoparticlesrevealed flagellin determinants of the polar flagellum, originallyshielded from their environment by an LPS sheath inthese bacteria .Significant progress has been made in the genetics of motility,plasmid biology, and the genome organization and dy-namics of Azospirillum bacteria . A newtype of social motility was revealed: spreading in a semiliquidmedium with the formation of microcolonies. It is such spreading that is of decisive importance when wheatroots are colonized by azospirilla, while swarming is thedominant mode of social motility under laboratory conditions. It was shown that external factors andspontaneous and induced changes in the genome, in particular,in the structure of megaplasmids, have a great influence onthe social behavior of the bacteria. The genome changes areaccompanied by phenotypic variations in the social motility ofazospirilla , andthey can lead to changes in the formation of biofilms and inthe early stages of plant-root colonization .Insertion elements responsible for the plasticity of A. brasilensemegaplasmids were described for the first time. Newknowledge was obtained on the primary structures and functionsof several such plasmids . Theinsertion elements ISAzba1 and ISAzba3, which mediate thefusion of the resident plasmid from A. brasilense Sp245 withforeign DNA, contribute to the enrichment of the Azospirillumgenome with genetic material. The genome dynamics ofA. brasilense has a significant effect on the structure of thebacterial LPSs and their antigenic properties, as well as on theresistance of these bacteria to heavy metals and nitrites . The Azospirillum genes that regulate motility,denitrification, and the production of LPSs and flagella havebeen identified. A collection of A. brasilense mutants, recombinantplasmids, and Escherichia coli strains containing clonedAzospirillum genes was established .Another component of the Azospirillum cell surface iscarbohydrate-binding proteins, lectins. These are importantstructures in the system of \u201crecognition\u201d and the establishmentof partnerships at the initial stages of associative bacterium\u2013plant relationships. Studies of Azospirillum lectins at theIBPPM RAS began in the second half of the 1980s . It was for the first time that lectins with interstraindifferences in carbohydrate specificity were found on the surfaceof azospirilla isolated from various sources (30 strains).It was revealed that lectins are distributed evenly on theouter membrane of the azospirilla and do not belong to anymorphological structures such as pili or flagella . The dependence of lectin activity in bacteria onculturing conditions was found. Conditions unfavorable forculture growth stimulated lectin activity and vice versa. Forthe first time, the role of Azospirillum lectins associated withthe outer membrane in the adhesion of the bacteria to wheatseedling roots was revealed. Bacterial lectins were found tointeract with exocomponents, components of the membranefraction, and root lectins of plant seedlings . Confocal laser scanning microscopy showed that thelocation of tritium-labeled Azospirillum lectins was confinedto the plasma membrane of wheat seedling root cells. At theinitial stages of interaction with the roots, lectins can elicit abroad range of biochemical responses that are part of plantsignaling systems .A dose-dependent effect (inhibiting or promoting) ofbacterial lectins on the germination of seeds of higher plantswas shown. The regulatory effect of Azospirillum lectins ona number of their own and plant hydrolytic enzymes was revealed. From the detected interactionof the polysaccharide-containing complexes of azospirilla withintrinsic lectins, as well as with surface-localized agglutinatingproteins of other soil microorganisms (bacilli and rhizobia),participation of these extracellular glycopolymers in Azospirillumaggregation and in interbacterial contacts during theformation of soil communities may be inferred.For the first time, the ability of azospirilla to reduce gold (III)(AuCl\u20134) and selenium (IV) (SeO2\u20133 ) to the elementary state with theformation of nanoparticles was described. A simple schemeof bacterial synthesis of selenium nanoparticles with extracellularlocalization was proposed .Various aspects of the azospirilla life are extensively studiedby modern instrumental methods, including various spectroscopyoptions: M\u00f6ssbauer, IR Fourier, and Raman scattering. Byusing glutamine synthetase isolated from A. brasilense Sp245cells as an example, the possibility of applying nuclear gammaresonance spectroscopy (57Co nuclei) to the examination ofthe structural organization of metal cation binding sites inactive centers of enzymes was shown . For the first time in relation to Azospirillum bacteria,the assimilation of iron and the composition and structure ofiron-containing cellular components were studied , and so were the interaction and metabolic transformationsof cobalt ions by A. brasilense cultures .The synthesis of poly-\u03b2-hydroxybutyrate (PHB) by azospirillais the most pronounced response to negative effectsin these bacteria. For the first time, changes in bacterial PHBaccumulation under prolonged exposure to stress and differencesbetween A. brasilense strains Sp7 (epiphyte) andSp245 (endophyte) in response to heavy metal stress wereshown . A reduced PHB content in 6-dayold biofilm formed by the flagella-free mutant A. brasilenseSp245.1610, as compared to the wild-type strain Sp245 wasshown by Tugarova et al. (2017). The decrease in PHB contentmay affect the formation and stability of Azospirillumbiofilms.It is known that under adverse living conditions plantsgain advantage if the protective rhizosphere associationscontain microorganisms that perform a wide range of functions,including plant nutrition, resistance to abiotic stresses,biocontrol (protection against pathogens), and the removal ofpollutants from soil . The lastfunction is performed by pollutant-degrading microorganisms.Azospirilla, possessing almost all the above properties, aretypical representatives of protective rhizosphere associations.Screening of Azospirillum strains from the CRM IBPPM allowedthe first detection of oil-oxidizing activity in some ofthem . Use of the A. brasilense SR80-wheat model showed that oil neither interferes with the plantgrowth-promoting activity of the micropartner nor affectsthe synthesis of bacterial IAA. A. brasilense SR80 showedchemotaxis not only toward root exudates of wheat but alsotoward crude oil . This strain wasalso resistant to the toxic effects of glyphosate and showeda consistently high level of IAA production in the presenceof the herbicide . On the basis ofthese results, a phytoremediation method was developed forhydrocarbon-contaminated soil in which A. brasilense SR80was used as one of the bacterial cultures for inoculatingplants (PatentRU 2403102). A. brasilense Sp245 associated with the rootsof wheat seedlings of cv. Saratovskaya 29 can transforminorganic forms of arsenic (arsenite to arsenate); owing tothis ability, the bacteria reduce the toxicity of the element.On the basis of A. zeae strain from the CRM IBPPM,employees of the Bionovatic group of companies developedand produced a biological product named Organit N, aimedat improving the nitrogen nutrition of plants (bionovatic.ru).According to the manufacturer\u2019s recommendations, the preparationis applicable to cereals, legumes, corn, and sugar beet.The high efficiency of artificial plant-microbial associationsestablished in vitro with the participation of azospirilla wasshown in the development of microclonal propagation technologiesfor plants to improve the quality of planting materialof crops and preserve rare plant species that are sources ofvaluable biologically active compounds .Despite the rather long period of studying Azospirillumbacteria, the interest of the world scientific community inthem does not wane; the number of publications dedicated toazospirilla has been steadily growing during the past decade,reaching 250 articles per year (according to www.scholar.google.com). The knowledge gained serves as a basis for expandingresearch on the variety of bacteria that form associationsand symbioses with plants. It is in this direction that theCRM IBPPM develops at present, and in this regard, the roleof such specialized collections can hardly be overestimated.As a result of IBPPM participation in the Russian-Europeanproject of the 7th Framework Program of the European Union\u201cBanking Rhizosphere Micro-Organisms\u201d , some strains of the Collection were included inthe pan-European database on rhizospheric microorganisms,designed to support both research on the rhizospheric microbiomeand practical biotechnology .It should be noted that the results described above wereobtained by modern methods, including those obtained in Russianand international projects: Russian Science Foundation,Russian Foundation for Basic Research, grants of the Presidentof Russia, state contracts within governmental programs,ISTC, INTAS, NATO, FP-7, etc. The obtained data formed thebasis for more than 80 candidate\u2019s and doctoral dissertationsdefended by researchers of the IBPPM. More than 600 articleswere published in Russian and international scientific journals. A scientific school was created under the guidance of ProfessorV.V. Ignatov, D. Sc. (Biol.), Honored Scientist of the RussianFederation. The school was repeatedly supported by grants ofthe President of the Russian Federation. Several inventions areprotected by patents of the Russian Federation. PGPR strainsand pollutant-degrading strains have become the subject ofintense interest from domestic small businesses.Thus, the example of the IBPPM Collection shows clearlythe significance of such special collections for the fundamentaland applied aspects of biological science.The authors declare no conflict of interest.Alen\u2019kina S.A., Bogatyrev V.A., Matora L.Yu., Sokolova M.K.,Chernysheva M.P., Trutneva K.A., Nikitina V.E. Signal effects ofthe lectin from the associative nitrogen-fixing bacterium Azospirillumbrasilense Sp7 in bacterial-plant root interactions. PlantSoil. 2014;381(1-2):337-349. 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Method of Phytoremediationof Soil Contaminated with Hydrocarbons (versions).Inventors: A.Ju. Muratova, A.D. Bondarenkova, S.N. Golubev,L.V. Panchenko, O.V. Turkovskaja. Appl. 15.05.2009. Publ.10.11.2010. Bull. No. 31. (in Russian)Peng G., Wang H., Zhang G., Hou W., Liu Y., Wang E.T., Tan Z.Azospirillum melinis sp. nov., a group of diazotrophs isolatedfrom tropical molasses grass. Int. J. Syst. Evol. Microbiol. 2006;56(6):1263-1271. DOI 10.1099/ijs.0.64025-0.Pereg L., de-Bashan L.E., Bashan Y. Assessment of affinity andspecificity of Azospirillum for plants. Plant Soil. 2016;399(1-2):389-414. DOI 10.1007/s11104-015-2778-9.Pozdnyakova L.I., Kanevskaya S.V., Levanova G.F., BaryshevaN.N., Pilipenko T.Yu., Bogatyrev V.A., Fedorova L.S. Taxonomicstudies of Azospirillum isolated from cereals in the Saratovregion. Mikrobiologiya= Microbiology (Moscow). 1988;57(2):275-278. (in Russian)Recommendations of the \u201cround table\u201d on the topic \u201cOn improvinglegislativesupport for the conservation of biological collectionsfor the development of the biotechnological industry of the RussianFederation\u201d. In: Issues of Legal Support for Scientific, Technicaland Innovative Activities: an informational and analyticalcompilation based on materials from an extended field sessionand a round table. Moscow: Publication of the State Duma,2011;176-180. (in Russian)Reinhold B., Hurek T., Fendrik I., Pot B., Gillis M., Kertsers K.,Thielemans D., De Ley J. Azospirillum halopraeferans sp. nov.,a nitrogen fixing organism associated with roots of kallar grass[Leptochloa fusca (L.) Kunth.]. Int. J. Syst. Bacteriol. 1987;37(1):43-51. DOI 10.1099/00207713-37-1-43.Shchyogolev S.Yu. On prokaryote taxonomy: topical problems andways out of the crisis. Vestnik Biotekhnologii i Fiziko-KhimicheskoyBiologii imeni Yu.A. Ovchinnikova = Yu.A. OvchinnikovBulletin of Biotechnology and Physical and ChemicalBiology. 2018;14(1):5-14. (in Russian)Schelud\u2019ko A.V., Makrushin K.V., Tugarova A.V., KrestinenkoV.A., Panasenko V.I., Antonyuk L.P., Katsy E.I. Changes inmotility of the rhizobacterium Azospirillum brasilense in thepresence of plant lectins. Microbiol. Res. 2009;164(2):149-156.DOI 10.1016/j.micres. 2006.11.008.Shelud\u2019ko A.V., Shirokov A.A., Sokolova M.K., Sokolov O.I., PetrovaL.P., Matora L.Yu., Katsy E.I. Wheat root colonizationby Azospirillum brasilense strains with different motility.Microbiology (Moscow). 2010;79(5):688-695. DOI 10.1134/S0026261710050140.Shirokov A.A., Budanova A.A., Burov A.M., Khlebtsov B.N., KrasovA.I., Shchyogolev S.Yu., Matora L.Yu. Immunoelectron microscopyinvestigation of the cell surface of Azospirillum brasilensestrains. Microbiology (Moscow). 2017;86(4):487-492.DOI 10.1134/S0026261717040142.Shirokov A.A., Krasov A.I., Selivanov N.Yu., Burygin G.L.,ShchegolevS.Yu., Matora L.Yu. Immunochemical detection ofazospirilla in soil with genus-specific antibodies. Microbiology(Moscow). 2015;84(2):263-267. DOI 10.1134/S0026261715020137.Tarrand J., Krieg N., D\u00f6bereiner J. A taxonomic study of the Spirillumlipoferum group with descriptions of a new genus Azospirillumgen. nov. two species, Azospirillum lipofeum (Beijerinck)comb. nov. and Azospirillum brasilense sp. nov. Can. J. Microbiol.1978;24(8):967-980. DOI 10.1139/m78-160.Tikhonova E.N., Grouzdev D.S., Kravchenko I.K. Azospirillumpalustre sp. nov., a methylotrophic nitrogen-fixing speciesisolated from raised bog. Int. J. Syst. Evol. Microbiol. 2019;69(9):2787-2793. DOI 10.1099/ijsem.0.003560.Tikhonovich I.A., Provorov N.A. Symbiosis of Plants and Microorganisms:The Molecular Genetics of the Agrosystems of theFuture. St. Petersburg, 2009. (in Russian)Tkachenko O.V., Evseeva N.V., Boikova N.V., Matora L.Yu., BuryginG.L., Lobachev Yu.V., Shchyogolev S.Yu. Improved potatomicroclonal reproduction with the plant-growth promoting rhizobacteriaAzospirillum. Agron. Sustain. Dev. 2015;35(3):1167-1174. DOI 10.1007/s13593-015-0304-3.Tugarova A., Mamchenkova P., Dyatlova Y., Kamnev A. Biochemicalstudy of selenite bioconversion by Azospirillum brasilense.FEBS Open Bio. 2018;8(S1):479-480. DOI 10.1002/2211-5463.12446.Tugarova A.V., Burov A.M., Burashnikova M.M., Kamnev A.A.Gold(III) reduction by the rhizobacterium Azospirillum brasilensewith the formation of gold nanoparticles. Microb. Ecol.2014a;67(1):155-160. DOI 10.1007/s00248-013-0329-6.Tugarova A.V., Shelud\u2019ko A.V., Dyatlova Yu.A., Filip\u2019echeva Yu.A.,Kamnev A.A. FTIR spectroscopic study of biofilms formedby the rhizobacterium Azospirillum brasilense Sp245 and itsmutant Azospirillum brasilense Sp245.1610. J. Mol. Struct.2017;1140:142-147. DOI 10.1016/j.molstruc.2016.12.063.Tugarova A.V., Vetchinkina E.P., Loshchinina E.A., Burov A.M.,Nikitina V.E., Kamnev A.A. Reduction of selenite by Azospirillumbrasilense with the formation of selenium nanoparticles.Microb. Ecol. 2014b;68(3):495-503. DOI 10.1007/s00248-014-0429-y.Tyagi S., Singh D.K. Azospirillum himalayense sp. nov., a nifHbacterium isolated from Himalayan valley soil, India. Ann. Microbiol.2014;64(1):259-266. DOI 10.1007/s13213-013-0658-1.Wisniewski-Dy\u00e9 F., Borziak K., Khalsa-Moyers G., Alexandre G.,Sukharnikov L.O., Wuichet K., Hurst G.B., McDonald W.H.,RobertsonJ.S., Barbe V., Calteau A., Rouy Z., Mangenot S.,Prigent-Combaret C., Normand Ph., Boyer M., Siguier P., DessauxY., ElmerichC., Condemine G., Krishnen G., Kennedy I.,Paterson A.H., Gonz\u00e1lez V., Mavingui P., Zhulin I.B. Azospirillumgenomes reveal transition of bacteria from aquatic to terrestrial environments. PLoS Genet. 2011;7(12):e1002430. DOI10.1371/journal.pgen.1002430.Xie C.-H., Yokota A. Azospirillum oryzae sp. nov., a nitrogen-fixingbacterium isolated from the roots of the rice plant Oryzasativa. Int. J. Syst. Evol. Microbiol. 2005;55(4):1435-1438. DOI10.1099/ijs.0.63503-0.Yang Y., Zhang R., Feng J., Wang C., Chen J. Azospirillum griseumsp. nov., isolated from lakewater. Int. J. Syst. Evol. Microbiol.2019;69:3676. DOI 10.1099/ijsem.0.003460.Yegorenkova I.V., Konnova S.A., Sachuk V.N., Ignatov V.V. Azospirillumbrasilense colonisation of wheat roots and the roleof lectin-carbohydrate interactions in bacterial adsorption androot-hair deformation. Plant Soil. 2001;231(2):275-282. DOI10.1023/A:1010340700694.Young C.C., Hupfer H., Siering C., Ho M.-J., Arun A.B., Lai W.-A.,Rekha P.D., Shen F.-T., Hung M.-H., Chen W.-M., Yassin A.F.Azospirillum rugosum sp. nov., isolated from oil-contaminatedsoil. Int. J. Syst. Evol. Microbiol. 2008;58(4):959-963. DOI10.1099/ijs.0.65065-0.Zhou S., Han L., Wang Y., Yang G., Zhuang L., Hu P. Azospirillumhumicireducens sp. nov., a nitrogen-fixing bacterium isolatedfrom amicrobial fuel cell. Int. J. Syst. Evol. Microbiol.2013;63(7):2618-2624. DOI 10.1099/ijs.0.046813-0.Zhou Y., Wei W., Wang X., Xu L., Lai R. Azospirillum palatumsp. nov., isolated from forest soil in Zhejiang province, China.J. Gen. Appl. Microbiol. 2009;55(1):1-7. DOI 10.2323/jgam.55.1."} +{"text": "Scientific Reports 10.1038/s41598-020-58551-0, published online 03 February 2020Correction to: This Article contains a typographical error in the Author Contributions section where,https://www.repository.naturalis.nl/record/707616. J.v.B. collected the tissue samples and performed the laboratory work in the laboratory of S. Steinfartz, Braunschweig. J.W.A. analyzed the data and wrote the manuscript with the help of J.v.B.\u201d\u201cJ.W.A. conceived and designed the study, and organized the species inventory. The files SI I and SI V are also available at should read:\u201cJ.W.A. conceived and designed the study, and organized the species inventory. J.v.B. collected the tissue samples and performed the laboratory work in the laboratory of S. Steinfartz, Braunschweig. J.W.A. analyzed the data and wrote the manuscript with the help of J.v.B.\u201dAs a result, the \u2018Data Availability\u2019 section,\u201cThe genotypic data for fire salamanders from Mayenne, France are presented in Supplementary Information II. The data for the Kottenforst, Germany are accessible at 10.5061/dryad.h0r6q.\u201dshould read:https://www.repository.naturalis.nl/record/707616\u201d\u201cThe genotypic data for fire salamanders from Mayenne, France are presented in Supplementary Information II. The data for the Kottenforst, Germany are accessible at 10.5061/dryad.h0r6q. The files SI I and SI V are also available at"} +{"text": "Luteovulum sphaeroides subsp. sphaeroides as the type species of Luteovulum gen. nov. This is because according to Rule 15 of the International Code of Nomenclature of Prokaryotes .a and carotenoids of the spheroidene series. Facultative aerobes and mesophilic. Phototrophic growth occurs on a number of organic substrates. The growth factors biotin, niacin and thiamine, alone or in combination, are required for growth. NaCl requirement is not required for growth; can tolerate up to 2\u20133% NaCl. C18:1\u03c97c/C18:1\u03c96C, C18:0, C16:0, C10:0 3OH, C16:1\u03c97C/C16:1 \u03c96c, C18;1\u03c97c11 methyl are the major fatty acids. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and an unidentified glycolipid are the major polar lipids. Hopanoids are not produced. Q10 is the major quinone. Delineation of the genus is based on 16S rRNA and rpoB gene-based phylogeny, phylogenomics, genome comparison and chemotaxonomic differences.Members can be isolated from freshwater ponds, paddy soils, wastewater treatment plants, alkaline ponds and lake sediments. Gram-stain negative, oval-to-rod shaped cells and have vesicular ICM architecture. Cells are mostly motile with a single polar flagellum and multiply by binary fission. Catalase and oxidase positive. Primarily phototrophic and contain BChl-sphaeroides.The type species is Luteovulum Description ofLuteovulum sphaeroides comb. nov.Luteovulum sphaeroides, resembling, similar; N.L. neut. adj. sphaeroides, spherical).Basonym:Rhodobacter sphaeroides (van Niel 1944) Imhoff et al. 1984Luteovulum sphaeroides is identical to that of Rba. sphaeroides .The type strain is ATH2.4.1Description ofLuteovulum sphaeroides subsp. sphaeroides subsp. nov.Luteovulum sphaeroides subsp. sphaeroides , resembling, similar; N.L. neut. adj. sphaeroides, spherical).Luteovulum sphaeroides subsp. sphaeroides is identical to that of Rba. sphaeroides . The 16S rRNA gene sequence GenBank/EMBL/DDBJ accession number of the type strain is X53853. The complete genome sequence accession numbers of the type strain are CP030271, CP030272, CP030273, CP030274, CP030275, and CP030276.The type strain is ATH 2.4.1Description ofLuteovulum sphaeroides subsp. megalophilum subsp. nov.Luteovulum megalophilum friend, loving; N.L. neut. adj. megalophilum, wide (temperature)-loving).Luteovulum sphaeroides subsp. megalophilum is identical to that of Rba. megalophilus . The 16S rRNA gene sequence GenBank/EMBL/DDBJ accession number of the type strain is AM421024 and that of the genome sequence is FZOV00000000.The type strain is JA194Description ofLuteovulum johrii comb. nov.Luteovulum johrii .Basonym: Rhodobacter johrii Girija et al. 2010Luteovulum johrii is identical to that of Rba. johrii and DSMZ (DSM 18678T). The 16S rRNA gene sequence GenBank/EMBL/DDBJ accession number of the type strain is AM398152 and that of the genome sequence is MABH00000000.The type strain, Description ofLuteovulum ovatum comb. nov.Luteovulum ovatum Basonym: Rhodobacter ovatus Srinivas et al. 2008Luteovulum ovatum is identical to that of Rba. ovatus . The GenBank/EMBL/DDBJ accession number of the 16S rRNA gene sequence of the type strain is AM690348 and that of the genome sequence is OAOQ00000000.The type strain is JA234Description ofLuteovulum azotoformans comb. nov.Luteovulum azotoformans ], nitrogen; N.L. pref. azo-, pertaining to nitrogen; L. part. adj. formans, forming; N.L. part. adj. azotoformans, nitrogen forming).Basonym: Rhodobacter azotoformans Hiraishi et al. 1997Luteovulum azotoformans is identical to that of Rba. azotofarmans . The GenBank/EMBL/DDBJ accession number of the 16S rRNA gene sequence of the type strain is D70846 and that of the genome sequence is QAOT00000000.The type strain is KA25Description ofLuteovulum alkalitolerans comb. nov.Luteovulum alkalitolerans .Basonym: Rhodobacter alkalitolerans Gandham et al. 2019Luteovulum alkalitolerans is identical to that of Rba. alkalitolerans . The 16S rRNA gene sequence GenBank/EMBL/DDBJ accession number of the type strain is LN810645.The type strain is JA916The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "There is an error in reference 18. The correct reference is: Sivan, D., Potasman, M., Almogi-Labin, A., Bar-Yosef Mayer, D.E., Spanier, E., Boaretto, E., 2006. The Glycymeris query along the coast and shallow shelf of Israel, southeast Mediterranean. Palaeogeogr. Palaeoclimatol. Palaeoecol. 233, 134\u2013148.There is an error in reference 31. The correct reference is: Braun, Y., Kagan, E., Bar-Matthews, M., Ayalon, A., Agnon, A., 2011. Dating speleoseismites near the Dead Sea Transform and the Carmel Fault: Clues to coupling of a plate boundary and its branch. Isr. J. of Earth Sci. 58, 257\u2013273.The sixth sentence of the fifth paragraph in the Results should have cited reference 36 instead of 35. As a result, all subsequent references are misnumbered. References 35\u201347 should be references 36\u201348.There is an error in the caption for"} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-020-59449-7, published online 13 February 2020Correction to: In the original version of this Article, Valeria Mezzano was omitted as a corresponding author. Correspondence about Immunophenotyping and Electron Microscopy should be addressed to Valeria.MezzanoRobinson@nyulangone.org.As a result, the Author Contributions statement:\u201cC.V. contributed to experimental design, data analysis and preparation of the manuscript and figures. V.M. contributed to experimental design, performed and supervised E.M. analysis, performed experiments, contributed to data analysis and preparation of manuscript and figures. N.K., F.S., D.E. and J.H. contributed to data analysis. V.M.M. performed experiments and contributed to data analysis. G.E.M. supervised the study, contributed to experimental design, performed experiments, contributed to data analysis and preparation of manuscript and figures.\u201dnow reads,\u201cC.V. contributed to experimental design, data analysis and preparation of the manuscript and figures. V.M. contributed to experimental design, performed and supervised E.M. analysis, performed experiments, contributed to data analysis and preparation of manuscript and figures. Queries regarding Immunophenotyping and Electron Microscopy should be addressed to V.M. N.K., F.S., D.E. and J.H. contributed to data analysis. V.M.M. performed experiments and contributed to data analysis. G.E.M. supervised the study, contributed to experimental design, performed experiments, contributed to data analysis and preparation of manuscript and figures.\u201dThese errors have now been corrected in the HTML and PDF versions of the original article."} +{"text": "Hyphalusshiyuensissp. nov. is described from Xisha Islands of China, which represents the ninth species and provides new distribution information for this unique intertidal genus. Brief comparisons between the new species and the known species are given. An updated key to the species of genus Hyphalus is provided. Hyphalus Britton, 1971 is a poorly known group of intertidal limnichid beetles and the sole genus in the subfamily Hyphalinae, which has a body shape more similar to Byrrhidae rather than Limnichidae. It was described by Limnichidae, Dryopidae, and Elmidae. The reason that Britton included it in Limnichidae as a subfamily was that \u201cI think it undesirable to add the number of families in the Dryopoidea where the family separation is already less marked than is usual\u201d . Specimens of described species examined in the study are deposited in the Australian National Insect Collection (ANIC). Specimens for dissection were prepared in 10% KOH for ca 12 hours, then dissected in glycerol on an open slide under a Leica Sapo stereomicroscope. Habitus was photographed using a Nikon DS-Ri2 mounted on a Nikon SMZ25; layers were captured and aligned in the NIS-Elements software. Individual structures in glycerol were photographed using a Zeiss AxioCam HRc mounted on a Zeiss AX10 microscope with the Axio Vision SE64 software. These images were then aligned in Helicon focus (v7.0.2). SEM images were taken using a Phenom Pro, then also aligned in Helicon focus. All the images were processed and plates were made in Photoshop CC 2019.All the studied specimens of the new species are deposited in the The terms used in morphological descriptions follow Hyphalus Britton, 1971: 88. Type species: Hyphalusinsularis Britton, 1971, by original designation.Hyphaluscrowsoni Hernando & Ribera, 2000: 240.Distribution: Seychelles, Aldabra Atoll.Hyphalusinsularis Britton, 1971: 90.Distribution: Australia, Queensland, Heron Island.Hyphaluskuscheli Britton, 1977: 82.Distribution: New Zealand, North Island.Hyphalusmadli Hernando & Ribera, 2004: 413.Distribution: Seychelles, Silhouette Island.Hyphalusprolixus Britton, 1977: 85.Distribution: New Zealand, North Island.Hyphalustaekoae Sat\u00f4, 1997: 110.Distribution: Japan, Ryukyus; China, Taiwan.Hyphalusultimus Britton, 1977: 85.Distribution: New Zealand, North Island.Hyphaluswisei Britton, 1973: 121.Distribution: New Zealand, North Island.Taxon classificationAnimaliaColeopteraLimnichidae17C22EC8-05B1-5718-A67B-5D415CEE3A1Dhttp://zoobank.org/B0F44404-362F-4045-A42C-177A595BE010Holotype: male, China, Hainan Province, Xisha, Shiyu Reef, in a small salty pool , 16\u00b032'42\"N, 111\u00b044'53\"E, alt. 0 m, 30.viii.2018, Qiang Xie leg. (SYSU). Paratypes: same data as holotype .Hyphalusinsularis Britton, 1971. Holotype: Herron I. Gt. Barrier Reef, Q. 24.xi.1968, beneath rocks below high-water mark. E. Britton, S. Misko (ANIC). Paratypes: same data as holotype .Hyphaluswisei Britton, 1973. Paratype: New Zealand Cape Rodney, North I. exposed rock platform opposite Goat I., N. of Leigh 5.xii.68, K.A.J. Wise . None types: Leigh, NZ G. Kuschel/ Hyphaluswisei Britton \u2642 .Hyphaluskuscheli Britton, 1977. Paratypes: In rock crevice at H. W. M. Napier Bay 6. III. 1945 J. M. GURR/ Bay of Islands Co. North I. ANIC); In rock crevice at H. W. M. below recent spring H. W. M. Napier Bay 6. III. 1948 J. M. GURR/ Bay of Islands Co. North I. (ANIC).Hyphalusprolixus Britton, 1977. Paratypes: In rock crevice below H. W. M. Otupoho Bay, Moturua, I. 26. III. 1945 J. M. GURR/ Bay of Islands Co. North I. .H.shiyuensis sp. nov. is the same length as the parameres (Fig. H.crowsoni and H.madli. It can also be distinguished from the Australian H.insularis and Japanese H.taekoae by the curved basal projection of the phallobase, which is similar to H.madli (The new species can be separated from the New Zealand species by the broadly ovate body shape. Additionally, the median lobe of aedeagus of res Fig. , thus diH.madli : fig. 1.Length 1.10\u20131.22 mm, width 0.62\u20130.69 mm. Body compact and nearly ovate (Fig. Head sub-rectangular, partly retracted in prothorax, not constricted behind eyes; lateral margins slightly curved, posterior margin slightly emarginated; vertex line and occipital incisions absent. Eyes small and very slightly protruding laterally, finely facetted. Antennae closely inserted in front of eyes; insertions concealed by small frontal expansions laterally. Antennae Fig. 11-segmePronotum transverse, ca 0.6 times as long as wide, widest just before posterior angles, lateral margins slightly curved, posterior margin bisinuate, anterior angles acute and extending forwardly, posterior angles acute and extending posteriorly; disc convex, with dense and fine punctations; lateral carinae complete, pronotal epipleuron wide. Prosternum with area before procoxae longer than prosternal process, anterior margin broadly curved; prosternal process broad and parallel sided, apex narrowed with truncate apical margin, extending into the cavities on mesoventrite Fig. . NotosteScutellum small and triangular. Elytra relatively broad, ca 1.1 times as long as wide, widest at about anterior third, lateral margins crenulate, apex with quadrangular projection that fits into incision of last ventrite. Dorsal surface weakly convex with fine punctations; epipleuron broad at base, extending to the apical projection. Hind wings absent. Mesoventrite short with pair of lateral depressions anteriorly and a large central concavity to receive the prosternal process, mesoventral process broad with posterior margin truncate; metaventrite short and nearly flattened, metanepisternum broad, meso-metaventral junction simple, of straight line; metendosternite with short and very broad strut, lateral arms slender, laminae and anterior tendons absent. Mesocoxae ovate and widely separated, trochantins exposed; mesocoxal cavities laterally open to mesepimeron, distance between cavities larger than width of cavities. Metacoxae ovate and widely separated, only a little wider than length. Legs all with brown enlarged femora, trochanters triangular and yellowish; tibiae flattened and expanded; tarsal formula 4-4-4, first three tarsomeres short and yellowish, last tarsomere elongate and enlarged apically with a pair of falciform claws, all with sparse long hairs underneath.Abdomen Figs , 12 withMale genitalia with aedeagus trilobate Fig. , phallobFemale unknown.Living in a small pool filled with sea water on a reef.The new species is named after Shiyu Reef, the type locality. The species name is an adjective.Only known from the type locality Fig. .Hyphalus, those from New Zealand are distinctly more elongated. After examining the specimens preserved in ANIC, we have found the antennae of H.insularis, H.wisei, H.kuscheli and H.prolixus are more or less asymmetrical rather than symmetrical (Hyphalus have asymmetrical antennal clubs and apical tubercles on elytra, although no specimen of H.ultimus was examined in this study. Hence, a more detailed study of the morphology of this genus is still needed.Among the nine described species of metrical and the Hyphalus is only known from Australia, New Zealand, Seychelles, Japan, and China with nine described species until now. The diversity of this genus, however, might be underestimated given the tiny body size and unique habitats of the species. More careful and comprehensive collection of beetles in the intertidal zones is needed to study the biogeography and dispersal methods of these interesting beetles."} +{"text": "Typhlocolenis Hoshina, 2008 in South Korea. Two new Korean species are described, under the names T.sillaensissp. nov. and T.jejudoensissp. nov. As a result of this study, the number of Typhlocolenis species is now five. A key to the species of the genus is provided.This is the first record of the genus Typhlocolenis belongs to the tribe Pseudoliodini Portevin, 1926 of the subfamily Leiodinae Fleming, 1812 of the family Leiodidae , Pseudcolenishilleri Reitter, 1885, and P.hoshinai Park & Ahn, 2007, have been recorded , Incheon, South Korea.All specimens used in this study were deposited in the National Institute of Biological Resources : KOREA, Gangwon-Prov. Pyeongchang-Gun, Mt. Odaesan, 22. vii. 2004, S.-J. Park leg. Paratypes, 2\u2642 1\u2640 (NIBR): 16. v. 2005, same data as holotype except for the date; 1\u2642 (NIBR): 21. ix. 2006, same data as holotype except for the date.Body length approximately 1.3\u20131.4 mm. Dorsum almost concolorous, brown, or dark brown. Head and pronotum strongly microreticulate, sparsely and very minutely punctate. Elytra almost smooth, sparsely and very minutely punctate, and densely and transversely strigose. The median lobe of aedeagus relatively thick and feebly curved at lateral margins and bearing a relatively small nipple at apex in dorsal view.Measurement of holotype. Body length: 1.39 mm; head length: 0.26 mm, width: 0.39 mm; pronotum length: 0.45 mm, width: 0.83 mm; elytron length: 0.81 mm, width: 0.83 mm.Coloration. Dorsum of body shiny and almost concolorous, brown or dark brown; antennae light brown; mesoventrite brown or dark reddish brown with a black median carina; metaventrite brown or dark reddish brown with a dark brown median carina; abdominal ventrites brown or dark reddish brown; legs brown with light brown tarsi.Body 1.31\u20131.39 mm in length, approximately 1.8 times as long as wide Fig. .Typhlocolenis is here first recorded in South Korea and is the only blind genus in the Korean Pseudoliodini. Therefore, T.sillaensis sp. nov. can be easily separated from Dermatohomoeus Hlisnikovsk\u00fd, 1963 and Pseudcolenis Reitter, 1885 of the tribe by the lack of eyes. Moreover, T.sillaensis sp. nov. can be distinguished from Dermatohomoeus and Pseudcolenis by having a metaventrite with a distinct median carina. In contrast, Dermatohomoeus and Pseudcolenis have no median carinae on the metaventrites.The genus Typhlocolenissillaensis sp. nov. is similar to T.fusca Hoshina, 2008 in appearance but can be distinguished by the relatively thick median lobe of aedeagus : KOREA, Jejudo Is., Jeju-City, Goepyeongioreum, 13. vi. 2005, S.-I. Lee leg. Paratypes, 3\u2640 (NIBR): same data as holotype; 1\u2642 5\u2640 (NIBR): Jejudo Is., Jeju-City, Bijarium, 12. vi. 2005, S.-J. Park leg.; 2\u2642 2\u2640 (NIBR): Jejudo Is., Jeju-City, Dongbaekdongsan, 13. vi. 2005, S.-I. Lee leg.; 2 exs. (NBIR): Jejudo Is., Jeju-City, Dongbaekdongsan, 22. v. 2006, S.-I. Lee & Y.-H. Kim leg.Typhlocolenissillaensis Hoshina & Park, sp. nov. Body length approximately 1.3\u20131.4 mm. Dorsum almost concolorous, brown to blackish brown. Head and pronotum strongly microreticulate, sparsely and very minutely punctate. Elytra almost smooth, sparsely and very minutely punctate, and densely and transversely strigose. The median lobe of aedeagus relatively thick, strongly expanded at about middle of lateral margins, and bearing a small nipple at apex in dorsal view.The present species very similar to Measurement of holotype. Body length: 1.30 mm; head length: 0.24 mm, width: 0.35 mm; pronotum length: 0.40 mm, width: 0.71 mm; elytron length: 0.73 mm, width: 0.73 mm.Coloration. Dorsum of body shiny and almost concolorous, brown to blackish brown; mesoventrite brown or dark reddish brown with a black median carina; metaventrite brown or dark reddish brown with a dark brown median carina; abdominal ventrites brown or dark reddish brown; legs brown with light brown tarsi.Body 1.28\u20131.42 mm in length, approximately 1.7 times as long as wide Fig. .Typhlocolenisjejudoensis sp. nov. is similar to T.sillaensis sp. nov. in appearance but can be distinguished by being strongly expanded at about middle of lateral margins in dorsal view (Fig. T.sillaensis sp. nov. has a very feebly curved median lobe in dorsal view (Fig. iew Fig. . In contiew Fig. .T.jejudoensis sp. nov. resembles T.furunoi Hoshina, 2008 in appearance but can be distinguished by median lobe of aedeagus with a small nipple at the apex in dorsal view (Fig. T.furunoi has a median lobe broadly rounded at the apex (Fig. Moreover, iew Fig. . In contpex Fig. .Typhlocolenisjejudoensis Hoshina & Park, sp. nov. is not known.The life history of Typhlocolenis is distributed only in East Asia (Fig. Typhlocolenis, T.uenoi Hoshina, 2008 has been collected only in caves (T.fusca specimens have sometimes been found in caves (Typhlocolenis have not been concurrently collected at one location. It is possible that the two Korean species, T.sillaensis sp. nov. and T.jejudoensis sp. nov. are endemic to the mainland of South Korea and Jejudo Island, respectively (Fig. The genus sia Fig. . Among ain caves . Others in caves . Currentely Fig. ."} +{"text": "The present review describes longitudinal studies of cognitive traits and functions determining the causes of their variations and their possible correction to prevent cognitive impairment. The present study reviews the involvement of such environmental factors as nutrition, prenatal maternal stress, social isolation and others in cognitive functioning. The role of epigenetic factors in the implementation of environmental effects in cognitive characteristics is revealed. Considering the epigenome significance, several studies were focused on the design of substances affecting methylation and histone modification, which can be used for the treatment of cognitive disorders. The appropriate correction of epigenetic factors related to environmental differences in cognitive abilities requires to determine the mechanisms of chromatin modifications and variations in DNA methylation. Transposons representing stress-sensitive DNA elements appeared to mediate the environmental influence on epigenetic modifications. They can explain the mechanism of transgenerational transfer of information on cognitive abilities. Recently, large-scale meta-analyses based on the results of studies, which identified genetic associations with various cognitive traits, were carried out. As a result, the role of genes actively expressed in the brain, such as BDNF, COMT, CADM2, CYP2D6, APBA1, CHRNA7, PDE1C, PDE4B, and PDE4D in cognitive abilities was revealed. The association between cognitive functioning and genes, which have been previously involved in developing psychiatric disorders , was revealed, thus indicating the role of the similar mechanisms of genetic and neural networks in both normal cognition and cognitive impairment. An important role in both processes belongs to common epigenetic factors. The genes involved in DNA methylation , histone modifications and chromatin remodeling are associated with increased risk of psychiatric diseases with cognitive deficiency together with normal cognitive functioning. The data on the correlation between transgenerational epigenetic inheritance of cognitive abilities and the insert of transposable elements in intergenic regions is discussed. Transposons regulate genes functioning in the brain due to the processing of their transcripts into non-coding RNAs. The content, quantity and arrangement of transposable elements in human genome, which do not affect changes in nucleotide sequences of protein encoding genes, but affect their expression, can be transmitted to the next generation. Recently, in addition to highly informative methods of molecularbiological research used for the identification of specificgenetic loci involved in cognitive functioning at the genomewidelevel, studies on the detection of genetic determinantsunder the longitudinal paradigm have become of great importance.Longitudinal studies make it possible to obtain specificobjective data on dynamics and to evaluate the contribution ofgenetic and environmental factors to the changes in cognitivedifferences in human ontogenesis. Cognitive abilities includeinformation perception (gnosis), speech, intelligence, memory,attention and praxis (motor skills) ,spatial perception ability, vocabulary, information processingspeed and executive functioning. Specific cognitive teststogether with multivariate genetic analysis were used to assessthem The results of meta-analyses of longitudinal studies demonstratedthat genetic factors , environmental influences , and age significantly affected cognitive development.The average changes in cognitive abilities during individualdevelopment were reported to increase significantly frominfancy to adolescence, and gradually decrease in adulthood. One of the first reports on a rapidincrease in the longitudinal stability of cognitive abilitiesfrom infancy to adolescence was reported by Bayley (1949).This study demonstrated a significant variability in generalintelligence in early childhood, which achieved relative stabilityby school age . The data presented wereconfirmed by a meta-analysis based on longitudinal studiesusing objective cognitive tests .This study examined the following cognitive abilities: generalintelligence, active vocabulary, verbal and nonverbal abilities(including IQ), selective and constant attention, working andspatial memory, visual attentiveness, and substitution of digitalsymbols. The results obtained in 15 independent longitudinalsamples revealed low to moderate correlations betweengenetic component and common (shared) environment andcognitive abilities in early childhood, while they increasedsharply and achieved a high level by adolescence until the lateadulthood. The correlations between individual environmentwere low in childhood and gradually increased to moderate inadulthood. Interestingly, an enhanced phenotypic stability ofcognitive abilities in child development was almost entirelymediated by genetic factors .A wide range of population and ontogenetic variability ofvarious cognitive abilities was demonstrated. For differentcognitive characteristics the average coefficient of geneticcorrelation was 0.6, while phenotypic correlation was 0.3.The highest level of heritability was reported for generalintelligence (factor \u201cg\u201d) \u2013 varying from 40 % in childhood to80 % in adults. The scholastic Assessment Test and AmericanCollege Test were used to measure these parameters . The changes in each of the cognitive abilitiesduring individual development are specific, with a uniquecontribution of environmental and genetic components. Forexample, the impact of common environment was 0.21 andof heritability coefficient was 0.51 for mathematical abilitiesmeasured by individual\u2019s ability to read and study mathematicsusing a combination of network tests. At the sametime, these values for reading ability (measured using theReading Efficiency Test (TOWRE), one of four tests from theTEDS analysis) were 0.14 and 0.66, respectively .Among all cognitive abilities, the study of intelligence ishighly significant, since validated tests estimating standardIQ indicators are used. For example, an individual withIQ < 50 is diagnosed with severe intellectual disability (ID),affecting 0.4 % of the population. About half of ID cases areobserved in chromosomal and monogenic diseases . Assortative mating accumulates genetic variancein the population in each generation, thus contributing to anadditive genetic variance of intelligence. Intelligence out ofmental psychopathology is normally distributed with a positiveresult of an exceptional characteristic representing a modelfor \u201cpositive genetics\u201d . Heritabilityof intelligence varies significantly depending on the studiedpopulation. For example, estimates of IQ heritability in twinstudies in Russia appeared to be higher than in comparablestudies from the USA. This observation is due to the similarity in living conditions of individuals from Russia. IQ heritabilityvaries depending on socio-economic status; it is significantlyhigher in high-income families. The difference in IQ amongAfrican Americans and European Americans in the UnitedStates was about one standard deviation (15 points of IQ) inthe 20th century, although recently it appeared to be decreased.Molecular genetic studies play an important role in assessingontogenetic variability in cognitive characteristics.In 2007, a meta-analysis of six longitudinal studies examiningthe role of hereditary factors in cognitive differences basedon two or more time intervals to minimize age variability wasconducted. An increasing contribution of heritability in cognitiveabilities was revealed from 13 (55 %) to 25 (70 %) years,which evidences a significance of interactions between thegenotype and the environment . In a2010, a meta-analysis involving 11,000 twin pairs demonstratedan enhanced heritable component in general cognitiveabilities from 41 % at 9 years to 55 % at 12 years and 66 %at 17 years. General cognitive abilities were assessed usingthe Stanford-Binet Intelligence Scale, including vocabularymeasurement, pattern analysis, memorizing sentences andnumbers, quantitative tests . The heritabilityof intelligence linearly increases from 20 % in theinfancy to 40 % in adolescence and 60 % in adulthood, withits maximum of 80 % in the elderly and further decreasing to60 % after 80 years. Genome-wide quantitative trait analysisand twin studies reported different levels of heritabilityfor certain cognitive abilities: 35 and 47 % for intelligence,respectively, 16 and 59 % for reading, 32 and 48 % for mathematicalabilities, 35 and 41 % for language skills .An increasing impact of the genetic component in cognitiveabilities from infancy to adolescence can be explainedby amplified and innovative effects in infancy. A large-scalemeta-analysis based on the results of 16 longitudinal studiesexamining the role of genetic and environmental componentsin cognitive functioning in 11,500 pairs of twins and siblingsassessed twice within the period from 6 months to 18 years,revealed that in early childhood innovative adaptation effectsprevail as a response to novel environmental stimuliand rapidly decrease by adolescence. The amplified effectscharacterizing the transfer of the influence of factors thatwere active in infancy to the subsequent stages in ontogenesisare amplified with further development. To measure cognitivecharacteristics in these studies, tests for intelligence andobjective knowledge were used .What are the mechanisms underlying individual differencesin cognitive abilities in ontogenesis? Some researchers suggestthat the stability in cognitive functioning over time is due tothe consistent exposure to the same exogenous environmentalfactors. Therefore, the stability of cognitive abilities reflectssocial, educational and economic stability. From anotherpoint of view, the stability of individual differences in cognitiveabilities in ontogenesis is due to the continuous effectof endogenous factors (genes), while exogenous influencesare irregular and have unstable effects. Thus, exogenous andendogenous factors, contributing to overall stability at differentdegrees differentially affect cognitive functions with age.The results of the genome-wide association study (GWAS)of cognitive abilities established several associations, andpolygenic estimates account for about 1 % of the variance incognitive functions. Different studies evidence a small effectof each genetic variant in cognitive development. However,polygenic score, which accumulates the effects of single DNAvariants to predict a genetic predisposition for each individual,can be estimated . Several studies reportedassociations of alleles with cognitive abilities, whichmay represent the basis for further experimental analysis onthe possible targeted effects on the products of these genes.From a clinical point of view, the study of neurotransmittersystems\u2019 genes in specific cognitive functions are of mostinterest, since it would help propose a pharmacotherapy ofcognitive impairment from the existing drugs.Genetic studies of individual cognitive abilities have beencarried out to identify the role of certain genes in cognitivedevelopment. The association analysis of SNPs with cognitiveabilities such as memory, educational background, and verbalnumericalabilities, revealed the involvement of genes thatplay an important role in brain development and functioning.These genes include CADM2 , CYP2D6 (encodes acytochrome metabolizing serotonin and neurosteroids) andAPBA1 (encodes a protein that interacts with the amyloid precursorin Alzheimer\u2019s disease). Verbal-numeric abilities weremeasured using a 13-point survey presented on a touch screencomputer. Memory was measured using the \u201cpair matching\u201dtask: participants observed a random grid of 12 cards withsix pairs of matching characters for 5 seconds. To measureeducational preparation, individuals were asked the question\u201cWhich of the following qualifications do you have?\u201d followedby a list of possible answers . In 2014,Das et al. observed significant main and interaction effectsof COMT and BDNF genotypes on reaction time . Alleles of the COMT gene are also associated withcognitive functions such as executive cognition and cognitivecontrol . The association ofalleles of the CHRNA7 gene with attention gating was detected \u2013 themeasurement was performed using H50 ERP . In 2019, a meta-analysis carried outwith the inclusion of 1.1 million mentally healthy individualsconfirmed the allelic association of the BDNF gene and phosphodiesterasesPDE1C, PDE4B, PDE4D with differences incognitive traits such as educational level and mathematicalabilities. The measurement was performed using normalizedcognitive test scores .In healthy individuals, associations of genes involved inthe development of psychiatric disorders with cognitive impairmentswere identified. GWAS was conducted involving78,308 people, and 336 SNPs were confirmed to be associatedwith cognitive functions. This study detected the involvementof genes associated with Alzheimer\u2019s disease (MEF2Cand EXOC4 genes) and schizophrenia . Themeasurement of fluid intelligence was carried out by variousquestionnaires (\u201ctouch screen\u201d or \u201cweb interface\u201d) with the number of correct answers of 13 questions . Cognitive impairment is comorbid to both mental andbehavioral disorders. For example, intelligence impairment isobserved in attention deficit hyperactivity disorder (ADHD). According to scientific data, ADHDis associated with genes responsible for the normal cognitivefunctioning. These genes include DRD4, SLC6A3 , and 5-HTTLPR .Their research is promising to clarify the mechanisms affectinggene networks involved in neurotransmitter systems functioningin normal and brain pathology cases. The commonality ofgenetic architecture of cognitive abilities and disabilities wasassumed. Hence, the data on cognitive pathology can possiblybe used for the study of cognitive abilities. It was also revealedthat genes involved in variations in normal intelligence areassociated with ID. According to the analysis of the OMIMdatabase, about half of all human genetic diseases have aneurological component, which frequently comprises ID.Molecular genetic studies of cognitive abilities and disabilities confirm the \u201cgeneralist geneshypothesis\u201d proposed by Professor Robert Plomin . According to this hypothesis, the same setof genes significantly affects different areas of cognitivefunctioning. In addition, individual variations and changesin general cognitive traits including reading and linguisticabilities tend to be mutually correlated, which indicates acommonality in their etiology .Cognitive impairments (CI) represent a heterogeneousgroup of diseases, which have been actively studied. Thegeneral mechanisms of these diseases together with the molecularprocesses underlying human cognition are identified.A significant role in these processes belongs to the genesencoding the proteins involved in epigenetic regulation. Theyparticipate in brain development and maintenance, necessaryfor adaptation to changing physical and social conditions.These genes were reported to be involved in both normal cognitivedevelopment and CIs with a pronounced genetic liabilityto autism spectrum disorders, ID, intellectual retardation, andschizophrenia. Fifty five genes with epigenetic influence wereidentified. They are divided into four categories: (1) writers,(2) erasers, (3) chromatin remodelers of the DEAD/H-ATPasefamily, and (4) other readers and chromatin remodelers.The writers include the genes involved in DNA methylation and involved in the addition ofamino acid residues to side groups of histones . Thelateral groups are molecules that attach to the central carbonatom of an amino acid residue, thus changing its biochemicalproperties. Therefore, the binding between histones and DNAmolecules is either enhanced or weakened. The erasers includethe HDAC4, HDAC8, KDM5C, KDM6A, and PHF8 genes.The products of these genes remove the lateral histone groups.Chromatin remodeling genes of the DEAD/H-ATPase familyinvolved in the regulation of the nucleosome position includethe ACTB, ARID1A, ARID1B, ATRX, CHD2, CHD7, CHD8,SMARCA2, SMARCA4, SMARCB1, SMARCE1, SRCAP, andSS18L1 genes. Other chromatin readers and remodulatorsinclude ASXL1, BCOR, CHMP1, CTCF, GATAD2B, HCFC1, KANSL1, MBD5, MECP2, PHF6, POGZ, SKI, MED12,MED17, MED23, NIPBL, RAD21, SALL1, SMC1A, andSMC3. The role of these genes in the etiology and pathogenesisof several CIs was revealed , whichcan represent the basis for future research into the possiblecorrection of ID using target therapy due to reversible natureof epigenetic modifications.Epigenetic mechanisms that are central in brain development,structure and functioning can affect changes in cognitivetraits in ontogenesis, since differences in gene expression areage- and cell-type specific . For example, aviolation of epigenetic regulation is observed in cognitive agingas a result of changes in DNA methylation, expression ofnon-coding RNAs (ncRNAs), and post-translational modificationof histones . Epigenetic mechanismsinclude DNA methylation, histone modifications, ATP-basedchromatin remodeling complexes, Polycomb-Tritorax proteincomplexes, ncRNAs, potential prions, transcription factorbinding and other mechanisms involved in the formationand maintenance of the inherited chromatin structure and itsattachment to the nuclear matrix . Epigeneticprocesses represent a reversible regulation of variousgenomic functions. They are necessary for tissue differentiationand long-term regulation of gene functions. Their dynamicchanges are caused by many factors including environmentalinfluences, variations in DNA sequences, and stochastic events.The study of the influence of hereditary and environmentalfactors on changes in DNA methylation is promising. Quantitativemeasurements of DNA methylation in the promoterregions of the dopamine D4 receptor (DRD4), serotonin transporter(SLC6A4) and monoamine oxidase A (MAOA) geneswere performed using DNA samples of 46 pairs of monozygoticand 45 dizygotic twins aged 5 to 10 years . The association of gene alleles and cognitive abilitieswas identified . It was found that differences in DNA methylation appearedeven in early childhood in genetically identical individualsand were unstable with time. The results of longitudinalstudies obtained suggest that environmental influences areimportant factors of individual changes in DNA methylationand differentially affect genomic structure. The observationof dynamic changes in DNA methylation over time underlinesthe importance of longitudinal studies of epigenetic factors. The analysis of DNA methylation of morethan 27,000 CpG sites in the genome of 387 individuals agedfrom 1 to 102 years showed a positive correlation between age andDNA methylation in different brain structures. Moreover, CpGislands, which demonstrated a pronounced constant correlationbetween DNA methylation and chronological age, wereidentified . These results evidence thatenvironmental factors have higher effects on DNA methylationin children compared to adults .During learning and memory formation, a dynamic regulationof the chromatin structure occurs in response to neuronalstimulation. Learning-induced chromatin changes includehistone modifications such as acetylation, phosphorylation and methylation. Moreover, non-histone proteins are involvedin chromatin modification, which play an important role inthe regulation of transcriptional activity of neurons duringmemory consolidation. These proteins include the subunitp65/ RelA of the NF-kB DNA binding complex, the transcriptionfactor p53, estrogen receptor alpha (ER\u03b1), DNA methyltransferase(DNMT1), tubulin, histone deacetylase (HDAC1),the glucocorticoid receptor, histone acetyltransferase p300/CBP Associated Protein .The role of environmental influences including nutrition,xenobiotics, stress in pre- and postnatal periods in cognitivedevelopment requires the involvement of epigenetic mechanismsin gene expression regulation during brain functioning. Nutrition can cause brain changes inontogenesis, comprising significant changes in cognitivefunctioning up to dementia. This effect is mediated by modifiedexpression of many genes, while individual nutritionalsensitivity depends on genetic variability. Thus, nutritionhas an immediate and lasting effects on the epigenome. Forexample, micronutrients such as folate, vitamins B6 and B12,choline and methionine are involved in DNA methylation.Other important environmental factors affecting the regulationof cognitive functions include exposure to opioids andother toxic substances in the prenatal period. A longitudinalstudy of children exposed to toxic substances demonstratedsignificant consequences even after 1, 2, 3, 41/2, 81/2 years,which represented a reduced IQ level compared to the controlgroup of children . The prenatal exposureto toxic substances affected cognitive development of childrendue to changes in epigenetic profile. In particular, the resultsfrom ADHD children indicate a correlation of paracetamolintake in pregnancy for more than 20 days with changesin the methylation profile at more than 1600 CpG islands. Maternal smoking during gestation isassociated with specific methylation of selected regions ofthe AHRR (aryl-hydrocarbon receptor repressor) and CYP1A1genes in their children with ADHD in the postnatal period.Longitudinal studies reported that children subjected toprenatal stress in the early stages of development were characterizedby a lower development rate and decreased cognitiveperformance in the first year of life . However, an elevated maternal cortisol levelat the end of pregnancy was associated with higher cognitivedevelopment and performance at the age of 12 months. Theseresults suggest that maternal cortisol and pregnancy-specificanxiety have a programmed effect on the developing fetus,which can be mediated by epigenetic factors . Social isolation in early childhood causes differentialcognitive development via an epigenetic effect on the expressionof genes involved in brain functioning, such as the BDNFgene .Thus, published findings indicate a crucial role of epigeneticfactors in cognitive development in ontogenesis.Each individual demonstrates a unique epigenetic responseto environmental stimuli, which manifests in an individuallevel of cognitive abilities. Therefore, the question as to the mechanisms of transgenerational transfer of epigenetic regulation of cognitive functions arises. It canbe assumed that transposable elements (TEs), which play animportant role in the regulation of epigenetic processes, canbe attributed to the structures involved in the transfer of thecognitive level to next generations . It was confirmed by transgenerational epigenetic programmingof individual personality traits from parents whoexperienced a severe environmental stress to their F3 andF4 generation . This observationcan be explained by TE stress-sensitivity, since novelgerminative insertions including stress reaction are transmittedto descendants . TE locationin the genome is reflected in their site-specific integrationsunder various factors, which specifically affect neurogenesis. It can be explained byTE influence on the expression of genes differentiating inhippocampal neuronal stem cells (NSC) . Indeed, high activity of TEs and their transfer under stress is cellspecific. These effects are associated withgenomic plasticity and cognition ,which are mediated by TE interaction with epigenetic factors,including ncRNAs .Changes in epigenetic regulation imply the absence of structuralrearrangements in the genome, since it mainly compriseshistone modifications, RNA interference, and DNA methylation.TEs can influence these mechanisms without modifyingnucleotide sequences in exons, but exerting their regulatoryeffect on gene expression via intergenic inserts . Ontogenetically,these properties contribute to tissue-specific differentiationof cells . With respect to hippocampalneurogenesis, the highest TE activity can be associated withepigenetic reprogramming of gene transcriptional activity forfunctional remodeling of differentiated neurons . Changesin the expression of the majority of LTR-containing TEs(endogenous retroviruses) were detected in mice by prenataladministration of valproic acid. It may explain a transgenerationaleffect of this drug on the delayed development of thenervous system and autism spectrum disorders . An important role in the regulatory effect of TEsbelongs to the processing of their transcripts to ncRNAs .A transgenerational transfer of epigenetic regulation ofmaternal cognitive abilities was based on stress and alcohol exposure of thedeveloping fetus .The changes are observed in F2 generation, since epigenetictransformation of the genome occurs in gametes in the prenatalperiod. The ncRNAs represent the most likely factors affectingtransgenerational transfer of cognitive abilities . At least 40 % ofall long ncRNAs are expressed in the human brain, of which,for example, KCN2AS, BC1/200, BDNF, GDNF, EPHB2,KCNA2, are involved in the regulation of synaptic plasticity. Changes in synaptic connections depending on individual experience areknown as synaptic plasticity, which plays an important role incognitive development . Transcriptsof long ncRNAs can be processed in miRNAs, whichplay an important role in the development of cognitive abilities. It was shown that dynamic changes in miRNAlevels affect the expression of genes involved in cognitivedevelopment such as memory and learning . The miRNAs interact with more than 90 % ofsynaptical proteins .The role of miRNAs in the transgenerational transmissionof cognitive abilities may be associated with their influenceon neuronal differentiation by changing the expressionprofile of certain genes . The miRNAlevels are specific in certain types of neurons . MiR-134 is involved in memory regulation byaffecting CREB expression . Prolongedexpression of miR-132 causes cognitive deficiency by inhibitingacetylcholinesterase activity ;miR-182 suppresses long-term memory by interacting withactin-regulatory proteins ; miR-124 affectslearning and memory by regulating mRNA expressionof GTPase-activating protein gene (IQGAP1) . MiR-2113 , miR-151a-3p, miR-212-3p, miR-1274b expressionlevels are associated with cognitive functioning. The studyof epigenetic factors in the transgenerational transmissionof cognitive abilities is promising for the development ofpreventive technologies of cognitive impairment in the nextgenerations. Empirical use of the natural resveratrol analoguephytoalexin by female mice prevented cognitive dysfunctionsin F1 and F2 generations due to changes in signaling pathwaysand epigenetic factors .To assess the ontogenetic variability in cognitive abilities, themolecular genetic studies with a longitudinal design of the obtaineddata have been conducted. Longitudinal studies provedthat an increasing phenotypic stability in cognitive abilities inhuman development was mediated by genetic factors. Higherimpact of the heritable component in cognitive developmentvaried from 41 % in children aged 9 years to 70 % in25-year-old individuals. In early childhood, the prevalence ofinnovative adaptation effects on environmental factors wasrevealed, whereas heritability level depends on the examinedcognitive ability. The association of CADM2, CYP2D6, andAPBA1 gene alleles with memory consolidation, educationalbackground, and verbal-numerical abilities was identified.Moreover, allelic variants of the BDNF and COMT genes areassociated with reaction time; CHRNA7, with attention gating;and BDNF, PDE1C, PDE4B, PDE4D, with educationallevel and mathematical abilities. In addition, an associationof the genes, previously demonstrated to be involved in thedevelopment of mental disorders , was determinedwith cognitive functioning in mentally healthy individuals.In the study of genes associated with cognitive impairment,the role of genes involved in epigenetic regulation was established.During the last years, the study of the effect of epigeneticfactors in cognitive differences appeared to be important, sincethey mediate the effect of environmental factors on cognitiondue to the chromatin regulation in dynamics. Epigeneticmodifications can demonstrate an immediate and a long-termeffect, both at the postnatal and prenatal periods. An importantrole in these effects is played by changes in DNA methylationat specific loci. It is assumed that transgenerational transmissionof cognitive abilities was caused by TEs. This is due totheir intergenic distribution and effect on the expression ofspecific ncRNAs. The importance of microRNAs for cognitivedevelopment suggests the possibility of their use as biomarkersand targets for potential therapeutic agents.The authors declare no conflict of interest.Abbott C.W., Rohac D.J., Bottom R.T., Patadia S., Huffman K.J.Prenatal ethanol exposure and neocortical development: a transgenerationalmodel of FASD. Cereb. Cortex. 2018;28(8):2908-2921.Aimone J.B., Li Y., Lee S.W., Clemenson G.D., Deng W., Gage F.H.Regulation and function of adult neurogenesis: from genes tocognition. Physiol. Rev. 2014;94(4):991-1026.Andrews S.J., Das D., Anstey K.J., Easteal S. 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Many Trichoderma species are the most prominent producers of SMs with antimicrobial activity against phytopathogenic fungi. Detailed information about these secondary metabolites, when grouped together, enhances the understanding of their efficient utilization and further exploration of new bioactive compounds for the management of plant pathogenic fungi. The current literature provides the information about SMs of Trichoderma spp. in a different context. In this review, we summarize and group different antifungal SMs of Trichoderma spp. against phytopathogenic fungi along with a comprehensive overview of some aspects related to their chemistry and biosynthesis. Moreover, a brief overview of the biosynthesis pathway, action mechanism, and different approaches for the analysis of SMs and the factors affecting the regulation of SMs in Trichoderma is also discussed.Phytopathogenic fungi, causing significant economic and production losses, are becoming a serious threat to global food security. Due to an increase in fungal resistance and the hazardous effects of chemical fungicides to human and environmental health, scientists are now engaged to explore alternate non-chemical and ecofriendly management strategies. The use of biocontrol agents and their secondary metabolites (SMs) is one of the potential approaches used today. Plant pathogens cause significant losses, which have obstructed efforts to increase agricultural production. In spite of remarkable achievements in the development of chemical pesticides, plant breeding technologies, and different cultural practices, as well as other management strategies for the control of plant pathogens, losses due to disease remain a limiting factor in agricultural production throughout the world, including many developed countries . Among pMagnaporthe oryzae) and soybean rust (Phakopsora pachyrhizi) in several Asian countries caused devastating yield losses and [U-14C] linoleic acid. It was suggested that the oxidization of linoleic acid to 13-hydroperoxide-diene, followed by 5-hydroxy-2,4-decenioc acid formation and finally esterification, resulted in the formation of pyrones [The pyrone 6-pentyl-2H-pyran-2-one (6-PP) ; 11 is a. viride , after warzianum ,57. It carzianum ,59. In sd fruits . In addidiseases and Fusaped soil . T. harzone 6-PP ; 12\u201315. umigatus ,63. In aa mellea . The ana species . Another96 mg/ml . Pyrone pyrones .T. harzianum [T. harzianum. Another butanolide, T39butenolide (18), was produced by a commercially available T. harzianum strain [Gaeumannomyces graminis var. tritici [G. graminis var. tritici at 200 mg/mL, while T39butenolide (18) inhibited the growth of G. graminis at 100 mg/mL. Additionally, harzianolide (16) and T39butenolide (18) caused growth inhibition in P. ultimum and R. solani [T. longibrachiatum Rifai aggr, 5-Hydroxyvertinolide (19) was isolated, which was antagonistic to the fungus Mycena citricolor, the agent responsible for American leaf spot disease of coffee [P. ultimum, R. solani, and B. cinerea [An antifungal butenolide compound, harzianolide ; 16, wasarzianum ,69,70. Tm strain . All of tritici ,71. Harzf coffee . In anot cinerea . The bio cinerea .T. harzianum in 1989. It contains a pyridine ring system with a 2,3-dimethoxy-4-pyridinol pattern [P. ultimum, G. graminis var. tritici [R. solani, and B. cinerea [T. harzianum exhibited weak antibacterial and antifungal activity and also showed high phytotoxicity in an etiolated wheat coleoptile bioassay analysis. The harzianopyridone (20) was also reported to cause necrosis in corn, bean, and tobacco in a concentration-dependent manner, which suggested that the two harzianopyridone (20) enantiomers may exhibit different activities [T. harzianum showed activity against Phytophthora cinnamomi, B. cinerea, and Leptosphaeria maculans [R. solani, F. oxysporum, and S. rolfsii [Antifungal harzianopyridone ; 20 was pattern . The rac tritici , R. sola cinerea . A laevotivities . In anotmaculans . This co rolfsii . The pyr rolfsii ,75.T. harzianum. These were isolated by the bioassay-guided fractionation of the butanol\u2013methanol extract of the fermentation broth of T. harzianum. T. harzianum was also found to produce another azaphilone, T22azaphilone (23). These compounds exhibited significant antifungal activity against P. ultimum, G. graminis var. tritici, and R. solani [B. cinerea, P. cinnamomi, and L. maculans at low doses [The azaphilones contain a chiral quaternary center and extremely high oxygenated bicyclic core, and hence form a structurally diverse group of SMs. Two azaphilone-type compounds, harziphilone ; 21 and . solani . T22azapow doses . Gene deow doses .Trichoderma produced a series of SMs, named koninginins A\u2013E and B (25) in their liquid cultures [T. koningii isolated from soil and fermented on a shredded wheat medium [T. harzianum and T. koningii [Trichoderma aureoviride [G. graminis var. tritici [F. oxysporum, Bipolaris sorokiniana, P. cinnamomi, and Pythium middletonii [Trichoderma koningiopsis YIM PH30002, exhibited antifungal activity against F. oxysporum, Fusarium solani, and Alternaria panax [Some species of nins A\u2013E ; 24\u201328 a species ,79. Two cultures . The totcultures ,81. Latecultures . The kont medium ,84. The koningii ,86 and keoviride . The tot tritici ,85, whilia panax . Koningiia panax .T. harzianum and T. koningii that showed antifungal activities against R. solani, S. rolfsii, M. phaseolina, and F. oxysporum [Trichoderma sp. YM 311505, exhibited strong antifungal activities against Pyricularia oryzae, C. albicans, Aspergillus niger, and Alternaria alternata with an MIC value of 32 \u00b5g/mL [Stigmasterol ; 30 was xysporum ,90. Two 32 \u00b5g/mL . T. harzianum strains that were active against R. solani, S. rolfsii, M. phaseolina, and F. oxysporum [G. graminis var. tritici and P. ultimum [Trichoderma against host resistance to other pathogens [Three anthraquinones, 1,8-dihydroxy-3-methylanthraquinone ; 33, 1-hxysporum . Compoun ultimum . It was athogens . T. cremeum. Along with the promotion of tomato seedling growth, this compound (36) also showed antifungal activities against R. solani, B. cinerea, and F. oxysporum [T. arundinaceum and showed an antibiotic effect against B. cinerea and Fusarium sporotrichioides. Beside its direct antibiotic effect, compound (37) also played an important role in the induction of plant resistance against phytopathogenic fungi. [T. cerinum [Rosellinia necatrix [The antifungal 10-member lactone cremenolide ; 36 was xysporum . Anotherc fungi. . Cerinol cerinum and shownecatrix .Fusarium and other fungal genera, like Trichoderma, Trichothecium, and Stachybotrys [T. brevicompactum and displayed significant inhibitory activity on R. solani, B. cinerea, and Colletotrichum lindemuthianum (EC50 = 25.60 g/mL) [T. harzianum and showed activities against several phytopathogenic fungi, such as Cochliobolus miyabeanus, R. solani, C. lindemuthianum, F. oxysporum, Thanatephorus cucumeris, Colletotrichum gloeosporioides, and B. cinerea [Trichothecenes are the sesquiterpenoid-derived SMs mainly produced by hybotrys ,98. The hybotrys . Trichothybotrys ,100. Trihybotrys ,100. It 60 g/mL) . It was cinerea ,102. Trichoderma spp. are briefly described here, and their structures are presented in T. harzianum [T. viride and showed antifungal activity against S. rolfsii [T. longibrachiatum and have been shown to have antifungal activities against C. albicans and P. oryzae [T. harzianum M10 strain, demonstrated remarkable biological properties, including plant growth promotion and antimicrobial activity against different plant pathogenic fungi, such as Pythium irregulare, Sclerotinia sclerotiorum, and R. solani [T. atroviride and showed activity against Phaeosphaerella theae with an MIC of 125 \u00b5g/disc [Other antifungal compounds belonging to different chemical classes isolated from arzianum and T. v rolfsii . Three a. oryzae . Harzian. solani . The cyc \u00b5g/disc . Trichoderma spp. for their antifungal activities against phytopathogenic fungi could be attributed to the combined action of SMs and hydrolytic enzymes [B. cinerea spore germination has been shown to be due to the synergetic effect of gliotoxin , terpene cyclases, non-ribosomal peptide synthetases (NRPSs), and hybrid PKS-NRPS enzymes, and are involved in the production of indole alkaloids, polyketides, terpenes, non-ribosomal peptides, and PKS-NRPS hybrids, respectively . The furresented .Trichoderma spp., different factors, such as pH signaling, velvet-complex proteins, and interactions with other organisms, are responsible for the expression of genes related to SMs [T. virens, T. reesei, and T. atroviride to the presence of R. solani were evaluated, and two PKSs were found among the genes induced in T. reesei\u2013R. solani and T. atroviride\u2013R. solani interactions, whereas all the genes in the biosynthesis cluster of gliotoxin were up-regulated [T. atroviride [T. arundinaceum and B. cinerea revealed an increase in the expression of tri biosynthetic genes [T. arundinaceum and B. cinerea, a secondary metabolite of B. cinerea, which is also a virulence factor of B. cinerea, reduced tri gene expression and harzianum A production in T. arundinaceum [Recent studies related to regulatory factors and the influence of environmental conditions on fungal SMs enhanced our understanding on the tightly regulated cellular process of SMs. Like other fungi, in d to SMs ,148,149.egulated . An up-rroviride . In anotic genes . Howeverdinaceum . Fusarium mycotoxin fusaric acid resulted in the suppression of 6-PP , and their associated intracellular signaling pathways. The pathway ,158,159.roviride .Trichoderma spp. has been used in plant protection as an environmentally friendly and efficient management tool against a variety of phytopathogens. This review presented the fungicidal SMs from Trichoderma spp. against phytopathogenic fungi. Some aspects of the structural overview of SMs and their biosynthesis were reviewed. Brief information on the biosynthesis pathway, action mechanism, different approaches for the analysis of SMs, and factors affecting the regulation of SMs in Trichoderma was also discussed. Fungi, being a most diverse group of phytopathogens, exert a huge impact on agriculture. High genetic flexibility and broad-spectrum lifecycles allow the pathogenic fungi to develop fungicide resistance and invade new hosts. Therefore, new management strategies are needed for fighting against pathogenic fungi. The utilization of SMs from"} +{"text": "Scientific Reports 10.1038/s41598-017-11351-5, published online 08 September 2017Correction to: The original version of this Article contained an error in the name of the author Jian Chen, which was incorrectly given as ChenJian Chen. In addition, in the Author Contribution statement and the supplementary material accompanying this Article, the first and last names of all the authors were inadvertently switched. The Author Contribution statement now reads:S.B.S. and Q.L.C. designed the research project. Y.M.L., M.W., Y.Q.L., J.C. and H.Z. performed all the experiments. Y.Y.L., Y.L.S., C.C.T. and Q.M.Z. conducted the bioinformatics analysis. Y.J.H. helped with the results analysis. Y.M.L. and Q.L.C. wrote the manuscript. All authors reviewed the manuscript.These errors have now been corrected in the HTML and PDF version of the Article, and in the accompanying supplementary material."} +{"text": "Nature Communications 10.1038/s41467-020-14709-y, published online 13 February 2020.Correction to: The original version of this article omitted from the author list the third author Sanja Sviben, who is from the \u201cDepartment of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany\u201d. Consequently, the new author list and affiliations are as follows:1, Elena Mac\u00edas-S\u00e1nchez1, Sanja Sviben1, Peter Fratzl1, Luca Bertinetti1*, Matthew J. Harrington1,2*\u201cFranziska Jehle1Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany. 2Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montr\u00e9al, QC H3A 0B8, Canada. email: luca.bertinetti@mpikg.mpg.de; matt.harrington@mcgill.ca\u201d.The Author contributions statement was changed to the following to add S.S.: \u201cM.J.H., L.B. and P.F. devised and oversaw the study. L.B., F.J., S.S. and E.M.-S. performed experiments and processed data. M.J.H. and F.J. wrote the paper. All authors contributed to editing the paper\u201d.This has been corrected in both the PDF and HTML versions of the article."} +{"text": "Hyperactive delirium is known to increase family distress and the burden on health care providers. We compared the prevalence and associated factors of agitated delirium in advanced cancer patients between inpatient palliative care and palliative home care on admission and at 3\u00a0days before death.This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients, which were performed at 23 palliative care units (PCUs) between Jan and Dec 2017, and on 45 palliative home care services between July and Dec 2017.p\u00a0<\u00a00.001) and 7.6% (6.4% \u2010 8.9%) vs. 5.4% (4.0% \u2010 7.0%) 3\u00a0days before death (p\u00a0<\u00a00.001). However, multivariate logistic regression analysis revealed that the place of care was not significantly associated with the prevalence of agitated delirium at 3\u00a0days before death after adjusting for prognostic factors, physical risk factors, and symptoms.In total, 2998 patients were enrolled and 2829 were analyzed in this study: 1883 patients in PCUs and 947 patients in palliative home care. The prevalence of agitated delirium between PCUs and palliative home care was 5.2% (95% CI: 4.2% \u2010 6.3%) vs. 1.4% (0.7% \u2010 2.3%) on admission (There was no significant difference in the prevalence of agitated delirium at 3\u00a0days before death between inpatient palliative care and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment. We enrolled 2998 patients in palliative care units and home care. A 169 patients were excluded due to the date of death is unknown. We analyzed 2829 patients: 1882 patients in palliative care units, and 947 patients in home care. Furthermore, pharmacotherapy and devices need to be developed to control agitated delirium at home, even if they cannot be used internally.To the best of our knowledge, no study has compared the prevalence of hyperactive delirium between PCUs and palliative home care at the same timing using the same assessment tool or explored associated factors considering the place of care and prognostic factors.Therefore, we compared the prevalence and associated factors of hyperactive delirium between advanced cancer patients admitted to PCUs and those in palliative home care in Japan on admission and at 3\u00a0days before death.2This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients who were receiving palliative care in PCUs or at home to addresses the dying process and end\u2010of\u2010life care in terminally ill cancer patients, especially to clarify the symptoms of and medical treatment for advanced cancer patients at the end of life. One study was performed at 23 PCUs between Jan 2017 and Dec 2017,The palliative care specialists in PCUs and the primary care physicians with expertise and experience in palliative care in home care were primarily responsible for each patient evaluated and recorded all measurements on the day of enrollment. The physician followed the patient until death or 6\u00a0months after enrollment, and the observation period ended when patients were discharged from PCUs or palliative home care either alive or dead. In general, physicians routinely assessed and recorded symptoms and treatments on a daily basis, but in some cases, they assessed and recorded them retrospectively after the observation period based on medical records and memory.Both studies were conducted in accordance with the ethical standards of the Declaration of Helsinki and the ethical guidelines for research presented by the Ministry of Health, Labour and Welfare of Japan. The institutional review boards of all participating services approved this study, and main institutional review boards approved the use of existing data for secondary analysis and their combination.3Eligible patients were enrolled consecutively when admitted to PCUs or starting palliative home care at the participating facilities. The eligibility criteria for the two studies were the same; (a) 18\u00a0years old or older, (b) locally advanced or metastatic cancer (including hematopoietic neoplasms), and (c) admitted to PCUs or started palliative home care at the participating facilities during the study period. Patients admitted to PCUs who were expected to be transferred or discharged within a week were excluded.4We used item 9 of the Memorial Delirium Assessment Scale (MDAS#9) to assess the subtypes and severity of delirium at the time of assessment.The physicians coded item 9 with \u201chyperactive features\u201d or \u201cmixed features\u201d based on the last few hours of observations. We assessed the presence of agitated delirium on admission and at 3\u00a0days before death. To adjust for background factors with a potential influence on the prevalence of agitated delirium at the time of assessment, we collected several other data on the day of enrollment based on previous studies and discussion among researchers,Similarly, we recorded several other data of symptoms and treatment before death, such as the dosage of opioids, fever, and parenteral hydration at 1\u00a0week before death, and symptom severity at 3\u00a0days before death.We also recorded the demographic and clinical characteristics of the participants, including the site of primary cancer, presence of bowel obstruction, and data to assess the Palliative Prognostic Index (PPI),5We analyzed patients with a known date of death. First, we conducted descriptive analyses of the demographic characteristics, and compared the prevalence of hyperactive delirium on admission and at 3\u00a0days before death between care settings using the chi\u2010square test or Fisher's exact test. Subsequently, we performed univariate logistic regression analysis of the prevalence of agitated delirium on admission and at 3\u00a0days before death between care settings.We next considered the impact of missing data. Although, the extent of missing data on admission was less than 1%, some data points before death were missing in more than 10%. Thus, we performed multiple imputation based on the missing data at random and the results for 20 imputations were pooled using normalizing transformations.Subsequently, we carried out multivariate logistic regression analysis to adjust for the patient background, symptoms, and treatment with a potential influence on the prevalence of agitated delirium on admission and at 3\u00a0days before death.As possible factors affecting the prevalence of agitated delirium on admission, we used the following independent variables based on previous studies and discussion among the authorsp\u00a0<\u00a0.05 and analyses were performed using SPSS\u2010J software .Significance was accepted at 6In total, 2998 patients were enrolled in both studies: 1896 patients in PCUs and 1102 patients in palliative home care. Among them, 169 patients were excluded due to an unknown date of death; 14 patients in PCUs and 155 patients in palliative home care. The remaining 2829 patients were analyzed. Two hundred and fifty\u2010seven patients in PCUs who were discharged survived and 293 patients in palliative home care discontinued their home care. . (Table\u00a0p\u00a0<\u00a00.001). among all patients, and there was significant difference between PCUs and palliative home care; 5.2% (95% CI: 4.2%\u20136.3%) vs. 1.4% (0.7%\u20132.3%) (6.2p\u00a0=\u00a00.006), but it was not significantly associated with the prevalence of hyperactive features at 3\u00a0days before death . , Male gender, central nervous system metastasis, and use of any catheter were significantly associated with the higher prevalence of agitated delirium on admission . . was one of the risk factors for delirium among cancer patients in PCUs.Of note, although a recent systematic review revealed the prevalence of hyperactive delirium in the palliative care setting to be 14% (0%\u201033%),Our results suggest that health care providers, especially in the home care setting, need to become proficient in dealing with agitated delirium before death. Furthermore, pharmacotherapy and devices need to be developed to control agitated delirium at home, even if they cannot be used internally.In terms of the direction for further studies to clarify the prevalence of hyperactive delirium in the palliative care setting, daily universal screening for delirium and analysis using a variety of adjustment factors is warranted.The current study had several limitations. First, we defined agitated delirium as being present when delirium was diagnosed using the DSM5 and classified into either the hyperactive or mixed type using item 9 of the MDAS on admission and 3\u00a0days before death. Therefore, we were unable to assess the presence of hyperactive delirium throughout the observation periods. In addition, we were unable to assess mixed\u2010type delirium patients who exhibited hypoactive features at the time of assessment. These reasons may explain the low prevalence of agitated delirium in our study. Second, we were unable to adjust for residual confounding factors affecting the development of agitated delirium at the time of assessment (e.g. use of corticosteroids and degree of cognitive impairment). The possibility that these factors affected the development of agitated delirium at the time of assessment cannot be excluded. For this reason, we were unable to conclude the definitive factors of agitated delirium at the time of assessment in advanced cancer patients in PCUs or palliative home care.Third, the symptoms and treatment during death were not always evaluated prospectively. Therefore, exploration of the potential effects of symptoms and treatment during death on the prevalence of agitated delirium at the time of assessment is required.Fourth, approximately one\u2010third of the palliative home care patients discontinued their home care, and most were hospitalized and died. The reasons for hospitalization were not assessed. Therefore, we were unable to assess the rate of home care patients admitted to the hospital due to agitated delirium at the time of assessment. However, we performed multiple imputation to minimize this limitation. Thus, the prevalence of agitated delirium at the time of assessment in palliative home care may be higher than reported. Future studies are needed to assess daily symptoms and clarify the prevalence of hyperactive delirium in palliative home care.Fifth, we defined agitated delirium at the time of assessment only based on item 9 of the MDAS, which has not been validated by the total MDAS score. A recent review noted MDAS as one of the best diagnostic tools8There was no significant difference in the prevalence of agitated delirium at 3\u00a0days before death between PCUs and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment.9This EASED study was supported in part by a Grant\u2010in\u2010Aid from the Japanese Hospice Palliative Care Foundation. The sponsor played no role in study design, collection, analysis, or interpretation of the data, writing of the report, or in the decision to submit the paper for publication.This study was performed in the Comparison of End\u2010of\u2010life trajectory in advanced cancer patient between inpatient hospice and home (Come Home study) and the East\u2010Asian collaborative cross\u2010cultural Study to Elucidate the Dying process (EASED).The participating investigators and study sites of Come Home study were as follows: Keijiro Miyake, M.D., Ph.D. (Keijiro Clinic), Manabu Tamura, M.D., Ph.D. , Junichiro Toya, M.D. (Sakura\u2010shinmachi Urban Clinic), Hiroto Shirayama, M.D. (Osaka Kita Home Care Clinic), Takamichi Matsuki, M.D., Ph.D. (Fujisawa\u2010Honmachi Family Clinic), Akihiro Ishikawa, M.D., (Ishikawa Rehabili Noushinkeigeka Clinic), Yasunori Muraoka, M.D. (Muraoka Home Clinic), Yasuhiro Saitou, M.D. (GP Clinic Jiyugaoka), Takahide Yamaguchi, M.D. (Yamaguchi Clinic), Tomohiro Nishi, M.D. , Nobuyuki Miyata, M.D. (Miyata Clinic), Masakatsu Shimizu, M.D., Ph.D. , Ryo Yamamoto, M.D. , Yousuke Kimura, M.D. (Yamato Clinic), Yoshiyuki Kamiyama, M.D. , Yasuyuki Arai, M.D., Ph.D. (Iki\u2010iki Clinic), Daishi Matsuo, M.D. (Margaret Clinic), Hideki Shishido, M.D. , Kazushi Nakano, M.D., Ph.D. (Nakano Zaitakuiryou Clinic), Kan Asahina, M.D. (Mutsumimachi Clinic), Maiko Haruki, M.D. (Orange Home\u2010Care Clinic), Keiko inoue, M.D. (Aisei clinic), Sen Otomo, M.D., (Seimeikan Clinic).The participating investigators and study sites of EASED were as follows: Satoshi Inoue, M.D. , Naosuke Yokomichi, M.D., Ph.D. , Hiroaki Tsukuura, M.D., Ph.D. , Toshihiro Yamauchi, M.D. , Akemi Shirado Naito, M.D. , Yu Uneno, M.D. , Akira Yoshioka, M.D., Ph.D. , Shuji Hiramoto, M.D. , Ayako Kikuchi, M.D. , Tetsuo Hori, M.D. , Yosuke Matsuda, M.D. , Hiroyuki Kohara, M.D., Ph.D. , Hiromi Funaki, M.D. , Keiko Tanaka, M.D., Ph.D. , Kozue Suzuki, M.D. , Tina Kamei, M.D. , Koji Amano, M.D. , Teruaki Uno, M.D. , Jiro Miyamoto, M.D. , Hirofumi Katayama, M.D. , Hideyuki Kashiwagi, M.D., MBA. , Eri Matsumoto, M.D. , Takeya Yamaguchi, M.D. , Tomonao Okamura, M.D., MBA. , Hoshu Hashimoto, M.D., MBA. , Shunsuke Kosugi, M.D. , Nao Ikuta, M.D. , Yaichiro Matsumoto, M.D. , Takashi Ohmori, M.D. , Takehiro Nakai, M.D. , Takashi Ikee, M.D. , Yuto Unoki, M.D. , Kazuki Kitade, M.D. , Shu Koito, M.D. , Nanao Ishibashi, M.D. , Masaya Ehara, M.D. (TOSHIBA), Kosuke Kuwahara, M.D. , Shohei Ueno, M.D. , Shunsuke Nakashima, M.D. (Oshima Clinic), Yuta Ishiyama, M.D. , Akihiro Sakashita, M.D., Ph.D. , Hana Takatsu, M.D. , Takashi Yamaguchi, M.D., Ph.D. , Satoko Ito, M.D. , Toru Terabayashi, M.D. , Jun Nakagawa, M.D. , Tetsuya Yamagiwa, M.D., Ph.D. , Akira Inoue, M.D., Ph.D. , Takuhiro Yamaguchi, Ph.D. , Mitsunori Miyashita, R.N., Ph.D. , Saran Yoshida, Ph.D. , Yusuke Hiratsuka, M.D., Ph.D. , Keita Tagami, M.D., Ph.D. , Hiroaki Watanabe, M.D. , Takuya Odagiri, M.D. , Tetsuya Ito, M.D.,Ph.D. , Masayuki Ikenaga, M.D. , Keiji Shimizu, M.D., Ph.D. , Akira Hayakawa, M.D., Ph.D. , Rena Kamura, M.D. , Takeru Okoshi, M.D., Ph.D. (Okoshi Nagominomori Clinic), Isseki Maeda M.D., Ph.D. , Tomohiro Nishi, M.D. , Kazuhiro Kosugi, M.D. , Yasuhiro Shibata, M.D. , Takayuki Hisanaga, M.D. , Takahiro Higashibata, M.D., Ph.D. , Ritsuko Yabuki, M.D. , Shingo Hagiwara, M.D., Ph.D. , Miho Shimokawa, M.D. , Satoshi Miyake, M.D., Ph.D. ), Junko Nozato, M.D. , Hiroto Ishiki, M.D. , Tetsuji Iriyama, M.D. , Keisuke Kaneishi, M.D., Ph.D. , Tomofumi Miura, M.D., Ph.D. , Yoshihisa Matsumoto, M.D., Ph.D. , Ayumi Okizaki, Ph.D. , Yuki Sumazaki Watanabe, M.D. , Yuko uehara, M.D. , Eriko Satomi, M.D. , Kaoru Nishijima, M.D. , Junichi Shimoinaba, M.D. , Ryoichi Nakahori, M.D. , Takeshi Hirohashi, M.D. , Jun Hamano, M.D., Ph.D. , Natsuki Kawashima, M.D. , Takashi Kawaguchi, Ph.D. , Megumi Uchida, M.D., Ph.D. , Ko Sato, M.D., Ph.D. , Yoichi Matsuda, M.D., Ph.D. (Department of Anesthesiology & Intensive Care Medicine / Osaka University Graduate School of Medicine), Yutaka Hatano, M.D., Ph.D. , Satoru Tsuneto, M.D., Ph.D. , Sayaka Maeda, M.D. , Yoshiyuki Kizawa M.D., Ph.D., FJSIM, DSBPMJ. , Hiroyuki Otani, M.D. .None of the authors have any financial or personal relationships to declare."} +{"text": "The genus Elymus L., together with wheat, rye, and barley, belongs to the tribe Triticeae. Apart from itseconomic value, this tribe is characterized by abundance of polyploid taxa formed in the course of remote hybridization.Single-copy nuclear genes are convenient markers for identification of source genomes incorporated intopolyploids. In the present work, a CAPS-marker is developed to distinguish basic St, H, and Y genomes comprisingpolyploid genomes of Asiatic species of the genus Elymus. The test is based on electrophoretic analysis of restrictionpatterns of a PCR-amplified fragment of the gene coding for beta-amylase. There are about 50 Elymus speciesin Russia, and most of them are supposed to possess one of three haplome combinations, StH, StY and StHY. BorealStH-genomic species endemic for Russia are the least studied. On the basis of nucleotide sequences from publicdatabases, TaqI restrictase was selected, as it produced patterns of restriction fragments specific for St, H, and Yhaplomes easily recognizable in agarose gel. A sample of 68 accessions belonging to 32 species was analyzed.In 15 species, the earlier known genomic constitutions were confirmed, but in E. kamoji this assay failed to revealthe presence of H genome. This unusual H genome was suggested to originate from a different Hordeum species.In 16 species, genomic constitutions were identified for the first time. Fifteen accessions from Asian Russiapossessed the genomic constitution StStHH, and E. amurensis, phylogenetically close to the StY-genomic speciesE. ciliaris, had the genomic constitution StStYY. It is inferred that the center of species diversity of the StH-genomicgroup is shifted to the north as compared to the center of origin of StY-genomic species, confined to China.Key words: Elymus; taxonomy; allopolyploids; genome constitution; CAPS markers. The genus Elymus L. is the largest in the tribe Triticeae Dum.and, according to different estimates, counts from 150 to 200species . It is representedonly by alloploid taxa with genome compositions includingseveral basic genomes (haplomes) in different combinations.The genetic basis of the genus Elymus is formed by five haplomesdescending from different genera of the tribe Triticeae:(St) Pseudoroegneria, (H) Hordeum, (P) Agropyron, (W)Astralopyrum, (Y) donor unknown. Genome constitution wasproposed as a stable genetic criterion for taxonomic classificationof Elymus species . Within a relatively shortspan of time, substantial changes occurred in the taxonomyof the tribe Triticeae on the basis of the genomic system ofclassification suggested by D.R. Dewey (1984). During thenext 20 years, six genera were identified according to variantsof genome constitution: Douglasdeweya C. Yen, J.L. Yang &B.R. Baum (PPStSt), Roegneria C. Koch (StStYY), AnthosachneSteudel (StStWWYY), Kengylia C. Yen & J.L. Yang(PPStStYY), Campeiostachys Drobow (HHStStYY), andElymus L. .However, departing from A. L\u00f6ve\u2019s principles, many botanistsstill attribute several genome combinations to the singlegenus Elymus s. l. With all this, genome constitutions are notyet determined in about 40 % of species .According to current evidence, 53 species of the genus Elymussubdivided into four sections occur in Russia . Two of the sections, Elymusand Goulardia (Husn.) Tzvelev, contain species with differentgenomic constitutions, which obviously contradicts thephylogenetic principle of their formulation. We suppose thatRussia is home to species with only three haplome combinations:StH, StY, and StHY . BorealStH-genomic endemics of Russia are less studied. Accordingto the taxonomic system based on the genome constitution, theElymus species should be attributed to three genera: Elymus,Roegneria, and Campeiostachys. However, in our view, thedivision of the species inhabiting Russia into three genera isimpractical due to the difficulties of morphologic identificationof these genera. With all this, taxonomic classification withinthe genus based on genome constitutions is indispensable forthe construction of a phylogenetically oriented taxonomy ofthe genus.Earlier, Cleaved Amplified Polymorphic Sequences (CAPS)markers were used to distinguish individual genomes in representativesof the tribe Triticeae . Some advantagesof CAPS markers are their codominance, moderate sensitivityto the amount of genomic DNA, and relatively low cost.We were first to use CAPS-markers to identify the genomicconstitutions of species of the genus Elymus . For this purpose, primers were designed based on theknown sequences of the gene coding for \u03b2 amylase , which included 38 sequences of haplome St, 23of haplome H, and 15 of haplome Y, belonging to 24 Elymusspecies. Of them, 14 species had the genomic compositionStStHH; 9, StStYY; and 1, StStHHUkUk (Elytrigia repens).Variable positions were sought that would discriminate representativesof an individual genome from the other two. Specialattention was paid to those genome-specific sequence variantsthat resulted in appearance/disappearance of recognition sitesfor restriction endonucleases. It was found that digestion ofthe PCR products with TaqI endonuclease resulted in the formationof genome-specific restriction patterns. In the presentwork, we apply CAPS analysis to a large sample of Elymusspecies from Asian Russia to reveal their genome constitutionsunknown hitherto.Plant material included 68 accessions of the species withknown (Table 1) and unknown (Table 2) genome constitutionsfound in Russia. The species nomenclature is given accordingto N.N. Tsvelyov and N.S. Probatova (2010). The accessionsanalyzed were received from the scientific collection of biologicalresources of the Central Siberian Botanic Garden SBRAS \u201cCollections of living plants indoors and outdoors\u201d; theiridentification numbers are given in Tables 1 and 2. Prefixescorrespond to the geographic origin of the accessions.2, 1 \u03bcM each of primers, 20 ng ofgenomic DNA, and 1 U of HS Taq DNA polymerase . The following settings were used: predenaturationat 94 \u00b0\u0421 for 4 min; 40 cycles: denaturation at 94 \u00b0\u0421 for 20 s,primer annealing at 60 \u00b0C for 25 s, elongation at 72 \u00b0\u0421 for90 s; postextension at 72 \u00b0\u0421 for 5 minutes. CAPS-analysis was made as follows: 8 \u03bcL ofthe PCR reaction mixture was mixed with MQ-H2O and TaqIbuffer up to 1\u00d7 concentration in a volume of 15 \u03bcL, and 1 unitof TaqI restrictase was added. Themixture was incubated at 65 \u00b0\u0421 for 1 hour and resolved in 1.7 % agarose gel in \u0422\u0410\u0415 buffer. Molecular weight marker:100+ bp DNA Ladder .Total DNA was extracted from 20 mg of dried green matterwith the use of NucleoSpin Plant II Kit according to manufacturer\u2019s recommendations. Amplificationof the \u03b2 amylase gene fragment was made in a C-1000thermocycler with the following primers:El_balg_F4 (5\u02b9-GGTACCATCGTGGACATTGAA- 3\u02b9) andEl_balg_R4 (5\u02b9-CTGTACCACCAGTGAATGCC-3\u02b9) . The PCR reaction mixture of 15 \u03bcL involume contained 1\u00d7 buffer for Taq polymerase, 0.2 mMeach dNTP, 1.5 mM MgClThe comparative analysis of sequences of the \u03b2 amylase genepublished in R. Mason-Gamer (2013) showed that the studiedfragment of Y genome of about 1100 bp in length did notcontain recognition sites for TaqI endonuclease, while St genomecontained one recognition site in the fragment of interestat a distance of about 170 bp from the primer El_balg_R4.The same site was present in some H genomes; besides, allH genomes contained a recognition site at a distance of about280 bp from the primer El_balg_F4. Visualized on gels, restrictionpatterns of the studied genomes were differentiatedaccording to the lengths of the longest fragments: \u041d genomewas distinguished by the presence of a band at about 650 bp;St genome, 930 bp; and Y genome, 1100 bp .Restriction patterns of the CAPS marker employed werestudied in 68 accessions . Electrophoretic patternsformed after TaqI digestion are shown in Fig. 2. Basedon the results of CAPS analysis, genomic constitutions of theaccessionsstudied were determined. Previously known genomicconstitutions were confirmed in 15 species of 16, E. kamojibeing the only exception. In 16 species, genomic compositionswere determined for the first time: 15 of them had thegenomic constitution StStHH, and one species, E. amurensis,had StStYY (Table 3). However, some limitations of the approachwere met. For example, in two accessions of E. kamojiCAPS-analysis revealed only two haplomes, St and Y , whereas it is known to be hexaploid accordingto the number of chromosomes, thus, it should contain threebasic genomes (haplomes). It is improbable that the absenceof restriction fragments corresponding to haplome H was dueto incomplete digestion. Since all representatives of the genuscontain St haplome, possessing a recognition site for TaqI endonuclease,the presence of St-specific fragments serves as an internal control for the completeness of hydrolysis. Accordingto the classification system based on genomic compositions,E. kamoji belongs to the genus Campeiostachys which embraces species with the genomic compositionStHY. In fact, we performed a cytological analysis, whichshowed that both accessions of E. kamoji possessed the chromosomenumber 2n = 42, corresponding to hexaploid. Thepresence of the H genome lacking two recognition sites forTaqI endonuclease in E. kamoji brings its origin into a question.It is not inconceivable that different representatives of the genus received their H genomes from different ancestorspecies, which agrees with the assumption of polyphyly of thedonors of basic haplomes .An interesting pattern of restriction fragments was observedin two accessions of E. confusus , with the genome constitution formerly determined asStStHH . In accession TAR-0730 , the longer fragment corresponding to the allele fromSt genome is truncated, possibly, as the result of a deletionor acquisition of an additional restriction site. The spectrumof restriction fragments in accession BUM-0505 lacks the fragment of about 930 bp characteristicof St genome, while the smaller fragment of about 170 bpcorresponding to this haplome is clearly seen. This phenomenonmight be attributed to a mutation in the St genome ofthe accession, for example, appearance of a recognition sitefor TaqI. Another possibility is a recombination and/or introgressionbetween genomes St and H in the course of intensemicroevolutionary processes indirectly confirmed by the highmorphologic variability within this species.According to the CAPS analysis undertaken in the presentwork, almost all newly studied accessions of the borealgroup of species from Siberia and Russian Far East have theStH genomic composition. One exception was E. amurensis,phylogenetically close to the StY-genomic species E. ciliarisand possessing the genome composition StY. This impliesthat the center of species diversity of the Asiatic StH-genomegroup is shifted to the north as compared to that of the StYgenomegroup, which is considered to be situated in China. In this context, it is worth noting that inNorth America, the genus Elymus is also represented mainlyby StH-genome species . Besides, in that territorya number of adventive Asiatic StHY- and StY-genomespecies were found .In general, the applied method showed a high accuracy: inthe present work earlier known genome constitutions wereconfirmed by CAPS analysis in 15 Elymus species of 16. For10 species, the genomic composition newly determined byCAPS analysis as StH, was independently corroborated bysequencing of a cloned fragment of the GBSS1 (waxy) gene. It should benoted that the sequencing of DNA from polyploid species hasa disadvantage, as it is rather laborious, requiring additionalgene cloning manipulations.The main advantage of CAPS markers is the ease of theirmethodic implementation, which permits one to analyzemany specimens with extensive morphologic and geneticvariability from broad ranges. The present work involvesCAPS analysis with the use of a fragment of the gene for \u03b2amylase and demonstrates rather good predictive power of themethod. However, it should be kept in mind that no molecularmarker taken by itself can unambiguously identify a genomeor species; it serves as a marker, not diagnostic. Therefore, thedevelopment of additional simple and accessible approachesfor genome identification in new and poorly studied biotypesfrom local habitats remains vital.The authors declare no conflict of interest.Agafonov A.V., Asbaganov S.V., Shabanova (Kobozeva) E.V., MorozovI.V., Bondar A.A. Genome constitution and differentiation ofsubgenomes in Siberian and Far Eastern endemic species of the genusElymus (Poaceae) according to the sequencing of the nucleargene waxy. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journalof Genetics and Breeding. 2019;23(7):817-826. DOI 10.18699/VJ19.555. (in Russian)Agafonov A.V., Kobozeva E.V., Asbaganov S.V., Shmakov N.A. Currentachievements and prospects of construction of a phylogeneticallyoriented taxonomy of the genus Elymus (Poaceae: Triticeae).Proceedings of the 14th International Scientific and Practical Conference\u201cProblems of Botany of Southern Siberia and Mongolia\u201d.Barnaul. 2015;314-322. (in Russian)Barkworth M.E. Changing perceptions of the Triticeae. In: JacobsS.W.L., Everett J. (Eds.). Grasses: Systematics and Evolution.Melbourne: CSIRO, 2000;110-120.Barkworth M.E., Cambell J.J.N., Salomon B. Elymus L. In: BarkworthM.E., Capels K.M., Long S., Anderton L.K., Piep M.B. (Eds.).Flora of North America. New York; Oxford: Oxford UniversityPress, 2007;24:288-343.Baum B.R., Yang J.-L., Yen C., Agafonov A.V. A taxonomic revision ofthe genus Campeiostachys Drobov. J. Syst. Evol. 2011;49(2):146-159.Dewey D.R. Synthetic Agropyron-Elymus hybrids. III. Elymus canadensis\u00d7 Agropyron caninum, A. trachycaulum and A. striatum.Amer. J. Bot. 1968;55:1133-1139.Dewey D.R. Cytogenetics of Elymus sibiricus and its hybrids withAgropyron tauri, Elymus canadensis and Agropyron caninum. Bot.Gaz. 1974;135:80-87.Dewey D.R. Cytogenetics of Agropyron ugamicum and six of its interspecifichybrids. Bot. Gaz. 1980;141:305-312.Dewey D.R. The genomic system of classification as a guide to intergenerichybridization with the perennial Triticeae. In: Gustafson J.P.(Ed.). Gene Manipulation in Plant Improvement. New York: PlenumPubl. Corp., 1984;209-279.Gostimsky S.A., Kokaeva Z.G., Konovalov F.A. Studying plant genomevariation using molecular markers. Russ. J. Genet. 2005;41(4):378-388. DOI 10.1007/s11177-005-0101-1.Hu C.Y., Tsai Y.Z., Lin S.F. Development of STS and CAPS markers forvariety identification and genetic diversity analysis of tea germplasmin Taiwan. Bot. Stud. 2014;55:12. DOI 10.1186/1999-3110-55-12.Jensen K.B. Cytology, fertility, and origin of Elymus abolinii (Drob.)Tzvelev and its F1 hybrids with Pseudoroegneria spicata, E. lanceolatus,E. dentatus ssp. ugamicus, and E. drobovii (Poaceae: Triticeae).Genome. 1989;32:468-474. DOI 10.1139/g89-470.Jensen K.B. Cytology and morphology of Elymus pendulinus, E. pendulinusssp. multiculmis, and E. parviglume (Poaceae: Triticeae).Bot. Gaz. 1990;151(2):245-251.Jensen K.B., Hatch S. Genome analysis, morphology, and taxonomyof Elymus gmelinii and E. strictus (Poaceae: Triticeae). Bot. Gaz.1989;150(1):84-92.Jensen K.B., Wang R.R.C. Cytogenetics of Elymus caucasicus andElymus longearistatus (Poaceae: Triticeae). Genome. 1991;34:860-867.Kobozeva E.V., Asbaganov S.V., Agafonov A.V. Genome compositionand assessment of the divergence between Russian boreal species inthe genus Elymus (Poaceae) detected on the basis of sequencingof the nuclear gene GBSSI. In: Prospects of Development and Challengesof Modern Botany. BIO Web Conf. 2018;11.00023. DOI10.1051/bioconf/20181100023.Kobozeva E.V., Mglinets A.V., Agafonov A.V. Identification of thegenomic composition in allopolyploid species of the genus Elymus(Poaceae: Triticeae) with CAPS-analysis. In: Proceedings ofthe 6th International Conference \u201cIssues in the Study of the VegetationCover in Siberia\u201d. Tomsk. 2017;155-157. DOI 10.17223/9785946216371/51. (in Russian)Konieczny A., Ausubel F.M. A procedure for mapping Arabidopsismutations using co-dominant ecotype-specific PCR-based markers.Plant J. 1993;4(2):403-410.Li X.-M., Lee B.S., Mammadov A.C., Koo B.-C., Mott I.W., Wang R.R.C.CAPS markers specific to Eb, Ee, and R genomes in the tribe Triticeae.Genome. 2007;50:400-411.Liu C.W., Dewey D.R. The genome constitution of Elymus fedtschenkoi.Acta Genet. Sinica. 1983;10:20-27.L\u00f6ve A. Conspectus of the Triticeae. Feddes Repert. 1984;95:425-521.Lu B.-R., Bothmer R. von. Interspecific hybridization with Elymushimalayanus and E. schrenkianus, and other Elymus species (Triticeae:Poaceae). Genome. 1992;35:230-237.Lu B.-R., Salomon B. Differentiation of the SY genomes in Asiatic Elymus.Hereditas. 1992;116:121-126.Lu B.-R., Salomon B., Bothmer R. von. Interspecific hybridization withElymus confusus and E. dolichaterus, and their genomic relationships(Poaceae: Triticeae). Plant Syst. Evol. 1995;197:1-17.Mason-Gamer R.J. Origin of North American Elymus (Poaceae: Triticeae)allotetraploids based on granule-bound starch synthase genesequences. Syst. Bot. 2001;26:757-768.Mason-Gamer R.J. Phylogeny of a genomically diverse group of Elymus(Poaceae) allopolyploids reveals multiple levels of reticulation.PLoS One. 2013;8(11):e78449. DOI 10.1371/journal.pone.0078449.Okito P., Mott I.W., Wu Y., Wang R.R. A Y genome specific STS markerin Pseudoroegneria and Elymus species (Triticeae: Gramineae). Genome.2009;52(4):391-400.Shavrukov Y.N. CAPS markers in plant biology. Russ. J. Genet.: Appl.Res. 2016;6(3):279-287. DOI 10.1134/S2079059716030114.Tsvelyov N.N. On the genus Elymus (Poaceae) in Russia. BotanicheskiyZhurnal = Botanical Journal. 2008;93(10):1587-1596. (in Russian)Tsvelyov N.N., Probatova N.S. The genera Elymus L., Elytrigia Desv.,Agropyron Gaertn., Psathyrostachys Nevski, and Leymus Hochst.(Poaceae: Triticeae) in the flora of Russia. In: V.L. Komarov MemorialLectures. Vladivostok: Dalnauka Publ., 2010;57:5-102. (inRussian)Zhou Y.-H., Wu B.-H., Fu T.-H., Zheng Y.-L. Morphology, fertility andcytogenetics of intergeneric hybrid between Roegneria kamoji Ohwiand Dasypyrum villosum (L.) Candargy (Poaceae: Triticeae). J. Syst.Evol. 1999;37(2):125-130."} +{"text": "Shivparvatia Pusalkar & D.K. Singh was described in 2015 and the specimen J.D. Hooker 11 deposited in K (K000742193) was designated as the lectotype of its type species S.glanduligera (Edgew.) Pusalkar & D.K. Singh (\u2261 Arenariaglanduligera Edgew.). Nevertheless, J.D. Hooker 11 (K000742193) is actually the type of S.ciliolata (Edgew.) Pusalkar & D.K. Singh (\u2261 Arenariaciliolata Edgew.). Thus the lectotypification of S.glanduligera was problematic and a re-lectotypification for this species is needed. One of the syntypes of S.glanduligera collected from Kashmir is selected here as its lectotype. Morphologically, S.ciliolata and S.glanduligera can be easily distinguished from each other by their different morphology of indumentum, disc gland and sepals, as well as the color of petals.The genus Arenaria L. s.l. includes over 300 species of herbs widely distributed from Northern Temperate to arctic regions Sadeghian & Zarre, with three species of subgenus Solitaria sampled in their study transferred to this new genus, viz. Solitariaciliolata (Edgew.) Sadeghian & Zarre, S.glanduligera (Edgew.) Sadeghian & Zarre, and S.stracheyi (Edgew.) Sadeghian & Zarre. They also lectotypified these species except S.glanduligera, but three syntypes of its basionym, viz. Arenariaglanduligera Edgew., were cited.Based on phylogenetic results, Solitaria to be a new genus and described it as Shivparvatia Pusalkar & D.K. Singh three months earlier than Shivparvatia has priority in taxonomy. Solitaria to their new genus, viz. Shivparvatiaciliolata (Edgew.) Pusalkar & D.K. Singh, S.glanduligera (Edgew.) Pusalkar & D.K. Singh, S.stracheyi (Edgew.) Pusalkar & D.K. Singh. They further designated the species S.glanduligera as the type of Shivparvatia and lectotypified S.glanduligera. However, they didn\u2019t lectotypify the other two species.On the other hand, J.D. Hooker 11 deposited in K , and the two specimens K000742194 and GH00353887 had been designated as the lectotype and isolectotype of S.ciliolata, respectively, by J.F. Duthie 2760, Fig. In 194 Fig. and K000194 Fig. were citShivparvatiaglanduligera by S.glanduligera, viz. Arenariaglanduligera, was published based on three specimens: H. Falconer s.n. , it is therefore selected.It is therefore obvious that the lectotypification of K, Fig. ; R. Stra K, Fig. . We therTaxon classificationPlantaeCaryophyllalesCaryophyllaceae(Edgew.) Pusalkar & D.K. Singh, J. Jpn. Bot. 90: 84. 201534818813-D3B8-589C-BAB6-E3155FF39213Arenariaglanduligera Edgew. in Edgew. & Hook. f., Fl. Brit. India 1: 240. 1874. \u2261 Lectotype (designated here): Kashmir, H. Falconer s.n. (K000742189, Fig. J.D. Hooker s.n. (K, Fig. R. Strachey & J.E. Winterbottom s.n. (K, Fig. K, Fig. ; Kumaon,S.glanduligera can be easily distinguished from S.ciliolata by its glandular pubescence, prominent disc gland, not pure white and usually violet petals, and scarious sepal margin. In contrast, the latter is characterized by its ciliate pubescence, small disc gland, entirely pure white petals, and thickened sepal margin (Morphologically, l margin ."} +{"text": "Scheffersomyces were identified during a diversity study of yeasts. All three are associated with insects and rotting wood in China. Phylogenetic analyses of a genomic dataset combining ITS and nrLSU revealed that these new collections are distinct from known species, thus three new species are introduced i.e. S.jinghongensis, S.paraergatensis, and S.anoplophorae. In our phylogenetic analyses, Scheffersomycesjinghongensis possesses a strong independent lineage and is closely related to S.titanus. S.paraergatensis is closely related to S.ergatensis, while S.anoplophorae is related to S.stambukii. Several differences in physiological traits and molecular data indicate that S.jinghongensis, S.paraergatensis, and S.anoplophorae are three newly identified species.Three species of Scheffersomyces Kurtzman. ex M. Suzuki. (2010) to include d-xylose-fermenting species in the Pichiastipitis clade, viz. P.segobiensis, P.spartinae, and P.stipitis. The genus Scheffersomyces was later expanded by including seven related Candida species as new combinations and by three novel species, S.illinoinensis, S.quercinus, and S.virginianus, which were discovered in rotting wood have been identified in wood-ingesting insects . Of the 19 valid species, five of them are known to form ascospores . This gecospores and 14 ocospores .Scheffersomyces are characterized by pseudohyphae formation, an inability to utilize nitrates, and the possession of the co-enzyme Q-9 agar plates and incubated at 25 \u00b0C for 3\u20134 days. Strains were isolated from the samples of rotting wood via the enrichment technique with YM broth, supplemented by 0.025% sodium propionate and 0.01% chloramphenicol (YM agar plates and preserved in 15% glycerol at -80 \u00b0C.Samples of insects and rotting wood were collected from Henan Province and Yunnan Province from 2015\u20132017. Strains of yeast were isolated from the insect guts according to the methods described by phenicol . All yeaCM) agar, YM agar, or 5% malt extract (ME) agar at 25 \u00b0C for 6 weeks . The nuc rDNA ITS1-5.8S-ITS2 (ITS) region was amplified using primer pairs ITS1/ITS4 . The D1/Saccharomycescerevisiae CBS 1171T was chosen as the outgroup after consulting The sequences obtained from this study and the reference sequences obtained from GenBank Table were aliPageBreakbootstrap replicates. The phylogenies from MP and ML analyses were displayed using Mega 7 and FigTree v1.4.3 branch swapping and 1,00e v1.4.3 , respectSaccharomycescerevisiae CBS 1171T), comprised of 1085 characters in the aligned matrix. Of these, 541 characters were constant, 356 variable characters were parsimony-uninformative, and 188 characters were parsimony-informative. The MP analysis resulted in three equally parsimonious trees; the first tree is shown in Fig. PageBreakPageBreakthree MP trees were identical, except for the species order within different clades. ML analyses revealed that tree topologies of the best tree were identical to those of the MP tree (not shown). The sequences of each three new species formed a well-supported monophyletic group . S.paraergatensis and S.anoplophorae were related to S.ergatensis and S.stambukii, respectively, while S.jinghongensis possessed a strongly independent lineage that is distinct from other species and included 26 in-group taxa and one out-group taxon refers to the geographical origin of the type strain of this species.The species name T.NYNU 17926China, Yunnan Province, Jinghong, in rotting wood, under a tropical rainforest, July 2017, K.F. Liu & Z.W. Xi .YM broth for 3 days at 25 \u00b0C and occur singly or in pairs after being placed in \u00b0C Fig. . Buddingnot Fig. . Asci orChina, Yunnan Province, Jinghong, in rotting wood, under a tropical rainforest, July 2017, K.F. Liu & Z.W. Xi, NYNU 17977.T ; additional isolate NYNU 17977 .holotype NYNU 17926S.jinghongensis were grouped in an independent lineage and are related to S.titanus and other Scheffersomyces species. The nucleotide differences between the new species and the close relative S.titanus refers to its phylogenetic similarity to S.ergatensis.The species name T.NYNU 16782China, Henan Province, Nanyang, in rotting wood, under a mixed forest, July 2016, K.F. Liu & Z.W. Xi .YM broth for 3 days at 25 \u00b0C and occur singly or in pairs after grown in a \u00b0C Fig. . Buddingres Fig. . GlucoseChina, Henan Province, Nanyang, in rotting wood, under a oak forest, August 2016, K.F. Liu & Z.W. Xi, NYNU 16969.T ; additional isolate NYNU 16969 .holotype NYNU 16782S.ergatensis and Candidabroadrunensis, which represent a new species, S.paraergatensis. The nucleotide differences between the new species and its closest relative, S.ergatensis, were 1.1% substitutions in the D1/D2 domain and 0.8% substitutions in ITS region, respectively. Similarly, PageBreakS.paraergatensis and C.broadrunensis displayed 0.9% substitutions in the D1/D2 domain and 2.4% substitutions in the ITS region, respectively. Physiologically, S.paraergatensis can be differentiated from its closest relative, S.ergatensis refers to the genus of the host beetle, Anoplophoraleechi.The species name T.NYNU 15730Anoplophoraleechi, in the People\u2019s Park, July 2015, R.C. Ren & K.F. Liu .China, Henan Province, Nanyang, in the gut of YM broth after 3 days at 25 \u00b0C. Budding is multilateral. After 3 days of growth on YM agar at 25 \u00b0C, the colonies are white to cream-colored, buttery, and smooth with entire margins. After 12 days at 25 \u00b0C on a Dalmau plate culture with CM agar, pseudohyphae were observed but true hyphae were not and occur singly or in pairs Fig. when planot Fig. . Asci orAnoplophoraleechi, in the People\u2019s Park, July 2015, R.C. Ren & K.F. Liu, NYNU 15733.China, Henan Province, Nanyang, in the gut of T ; additional isolate NYNU 15733 .holotype NYNU 15730PageBreakS.anoplophorae, were clustered in a well-supported clade and were phylogenetically related to S.stambukii , and determined that the genus Scheffersomyces is polyphyletic. S.spartinae was placed in a clade with Spathasporapassalidarum, distinct from the type species S.stipitis, although this placement was weakly supported by statistical PageBreakanalyses. However, COXII, and MtSm) with 14 described species. These results were later supported by S.stipitis (the type species), S.coipomoensis, S.shehatae, and their related species, (ii) S.stambukii and S.anoplophorae (described in this paper) and (iii) S.gosingicus, S.spartinae, and C.thasaenensis. These results suggest that the genus Scheffersomyces should be limited to species of the group comprising the type species S.stipitis. The remaining two groups, which have previously been considered members of Scheffersomyces, could become two novel genera, although their phylogenetic relationships with other genera were not fully examined by this study . Since iScheffersomyces have been found to occupy habitats rich in xylose, including rotting wood (Yeasts of the genus ing wood , wood-feing wood , and theing wood . We haveing wood , includiing wood . These ying wood . Surveyi"} +{"text": "Scientific Reports 10.1038/s41598-019-43934-9, published online 20 May 2019Correction to: The original version of this Article contained errors in the spelling of the authors Eva Poland, Tobias H. Donner, Kai-Markus M\u00fcller, David. A. Leopold & Melanie Wilke which were incorrectly given as E. Poland, T. H. Donner, K. \u2013M. M\u00fcller, D. A. Leopold & M. Wilke respectively.These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-020-59447-9, published online 14 February 2020Correction to: In the original version of this Article, Z. Song and Y. Bi were omitted as equally contributing authors.Additionally, the original version of this Article contained an error in the Author Contributions section.\u201cZ. Song and Y. Bi designed experiments; Z. Song, J. Zhang and H. Yang collect soil samples; Z. Song, J. Zhang and Y. Gong carried out experiments; Z. Song and J. Zhang analyzed experimental results. Z. Song and Y. Bi wrote the manuscript.\u201dnow reads:\u201cZ. Song and Y. Bi contributed equally to this work. Z. Song and Y. Bi designed experiments; Z. Song, J. Zhang and H. Yang collected soil samples; Z. Song, J. Zhang and Y. Gong carried out experiments; Z. Song and J. Zhang analyzed experimental results. Z. Song and Y. Bi wrote the manuscript.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Bacillus cereus in vacuum packed potato puree. Int. J. Food Sci. Technol. 41, 878\u2013884. doi: 10.1111/j.1365-2621.2005.01129.x\u201d It should be \u201cRajkovic, A., Uyttendaele, M., Courtens, T., Heyndrickx, M., and Debevere, J. (2006). Prevalence and characterisation of Bacillus cereus in vacuum packed potato puree. Int. J. Food Sci. Technol. 41, 878\u2013884. doi: 10.1111/j.1365-2621.2005.01129.x\u201d And the citation Andreja et al., 2010 in the INTRODUCTION Paragraph 1 should read: \u201c. Prevalence and characterisation of vere, J. . PrevaleBacillus cereus is common in the environment but emetic toxin producing isolates are rare. J. Appl. Microbiol. 100, 7\u201314. doi: 10.1111/j.1365-2672.2005.02764.x\u201d It should be \u201cAltayar, M., and Sutherland, A. D. (2006). Bacillus cereus is common in the environment but emetic toxin producing isolates are rare. J. Appl. Microbiol. 100, 7\u201314. doi: 10.1111/j.1365-2672.2005.02764.x\u201d And the citation Altayar and Sutherland, 2010 in the INTRODUCTION Paragraph 1 should read: \u201c. d, A. D. . BacilluFEMS Immunol. Med. Microbiol. 51, 8\u201313. doi: 10.1111/j.1574-695x.2007.00305.x\u201d It should be \u201cWang, S., Duan, H., Zhang, W., and Li, J. W. (2007). Analysis of bacterial foodborne disease outbreaks in China between 1994 and 2005. FEMS Immunol. Med. Microbiol. 51, 8\u201313. doi: 10.1111/j.1574-695X.2007.00305.x\u201d And the citation Wang and Zhang, 2013 in the INTRODUCTION Paragraph 1 should read: \u201c. Analysis of bacterial foodborne disease outbreaks in China between 1994 and 2005. Bacillus cereus food-borne isolates. Appl. Environ. Microbiol. 74, 850\u2013860. doi: 10.1128/AEM.01495-07\u201d It should be \u201cCardazzo, B., Negrisolo, E., Carraro, L., Alberghini, L., Patarnello, T., and Giaccone, V. (2008). Multiple-locus sequence typing and analysis of toxin genes in Bacillus cereus food-borne isolates. Appl. Environ. Microbiol. 74, 850\u2013860. doi: 10.1128/aem.01495-07\u201d And the citation Barbara et al., 2008 in the DISCUSSION Multilocus Sequence Typing and Genetic Diversity Paragraph 1 should be \u201c. Multiple-locus sequence typing and analysis of toxin genes in \u201c.In the original article B. cereus\u201d in the manuscript may lead to misunderstanding. Besides, we think that the references on the foodborne outbreaks and pathogenic concentration of Bacillus cereus were not specific enough, so we prefer to add two more references . The strains in the literatures we referenced to were not all isolated from food poisoning outbreaks, so our statement \u201cOutbreaks with vomiting and diarrheal syndromes caused by The corrections have been made to INTRODUCTION Paragraph 1:Bacillus cereus is a Gram-positive, spore-forming opportunistic pathogen that is widespread in different environments and known to cause foodborne outbreaks in humans of these cases, leading to six deaths (Wang et al., \u201cBottone, . B. cereThe authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The authors wish to make the following erratum to this paper .Request to exclude author Nestor Norio Oiwa from the authorship. The corrected list of authors should be: Emilia Longhi Bitencourt, Dora Fix Ventura and Marcelo Fernandes Costa.The change of authorship was caused by a lack of communication between the listed authors and Nestor Norio Oiwa after some changes within the team.Due to the authorship changes, the authors would like also to request Author Contribution section correction. A corrected Author Contribution section is provided below:Author Contributions: Conceptualization, E.L.B. and M.F.C.; methodology, D.F.V. and M.F.C.; investigation, E.L.B.; resources, D.F.V. and M.F.C.; data curation, E.L.B. and M.F.C.; writing\u2014original draft preparation, E.L.B. and M.F.C.; writing\u2014review and editing, M.F.C.; funding acquisition, D.F.V. and M.F.C. All authors have read and agreed to the published version of the manuscript.These changes do not influence the results, discussion, or conclusions. The authors would like to apologize for any inconvenience caused to the readers by this error."} +{"text": "This review presents the current progress in and approaches to in vitro conservation of reproductivecells of animals, including birds, such as cryopreservation and freeze-drying, as well as epigenetic conditions forrestoringviable spermatozoa and female gametes after conservation. Cryopreservation is an effective way to preservereproductive cells of various species of animals and birds. In vitro gene pool conservation is aimed primarilyto the restoration of extinct breeds and populations and to the support of genetic diversity in populations proneto genetic drift. It is the combination of ex situ in vivo and ex situ in vitro methods that can form the basic principlesof the strategy of animal genetic diversity preservation. Also, use of cryopreserved semen allows faster breedingin industrial poultry farming. Despite numerous advances in semen cryobiology, new methods that can more efficientlyrestore semen fertility after cryopreservation are being sought. The mechanisms underlying the effect ofcryopreservation on the semen parameters of cocks are insufficiently understood. The review reflects the resultsof recent research in the field of cryopreservation of female and male germ cells, embryonic cells, the search fornew ways in the field of genetic diversity in vitro (the development of new cryoprotective media and new conservationtechnologies: freeze-drying). Molecular aspects of cryopreservation and the mechanisms of cryopreservationinfluence on the epigenetic state of cells are highlighted. Data on the results of studies in the field of malereproductive cell lyophilization are presented. The freeze-drying of reproductive cells, as a technology for cheaperaccess to the genetic material of wild and domestic animals, compared to cryopreservation, attracts the attentionof scientists in Japan, Israel, Egypt, Spain, and France. There is growing interest in the use of lyophilized semenin genetic engineering technologies. Methods of freeze-drying are developed taking into account the species ofbirds. Organizational and legal ways of solving the problems of in vitro conservation of genetic resources of farmanimals, including birds, are proposed. The conservation of genetic resources of farm animals is aglobal challenge, and it attracts efforts of the world community.The Food and Agriculture Organization (FAO) ofthe United Nations and its specialized units coordinate theseefforts .Conservation programs for genetic resources include thefollowing tasks: economyc ;social and cultural issues; conservation of biodiversity; andthe maintenance of resources for academic or educationalpurposes, genetics, genomics, and adaptation to climate andother environmental changes.The method of ex situ in vitro gene pool preservationthrough cryogenic maintenance (cryobank) of cells or tissuesthat can be used for breed/population restoration is recognizeda necessary supplement to the in vivo method . It isthe combination of ex situ in vivo and ex situ in vitro methodsthat can form grounds for an effective strategy for preservinganimal genetic diversity.Methods developed to freeze reproductive cells of malefarm birds can be successfully applied to wild species to preservetheir genetic diversity: red jungle chicken , capercaillie , and pheasant. Due to the significant decrease ingenetic diversity in pure lines of industrial crosses , the use of cryopreserved semen of the best representativesof a line or breed in artificial insemination underconditions of poultry industry expands the range of variationand accelerates breeding.At present, cryopreservation of reproductive cells of males isthe most important, practically the only method of preservingthe gene pool of farm birds in vitro. Various protocols havebeen developed for the conservation of poultry semen, and theeffectiveness of their use depends on many factors . The problem of reduced functionalability of the semen after a freeze-thaw cycle has notyet been resolved; the level of the fertilizing abilityof thawedsemen is not satisfactory. According to different authors,depending on the freezing methods, individual and breedcharacteristics of chickens, egg fertilization varies from 2 to 85 % . The average level offertilization with cryopreserved semen is low, usually lessthan 30 % ; however, some recent publicationsshow 65 % average fertility of frozen-thawed semen . The reduced viability of embryos derivedfrom cryopreserved semen caused by DNA fragmentation alsocompromises the economic feasibility of its use for practicalbreeding purposes. Therefore, works aimed at the improvementof the composition of diluents for cryopreservation, theselection of cryoprotectant and freezing methods (in straws orpellets), the freezing protocols (low/fast), and so on are stillunder way .Most studies on cryopreservation of avian semen are conductedwith mixed ejaculates from several males, although itis known that the genetic contributions of males differ due tothe effect of selective fertilization ,and males have different quality indicators of sperm aftercryopreservation . Therefore,there are concerns that the use of cryopreserved sperm maylead to an increase in inbreeding when using mixed sperm.In order to avoid this problem, when preserving rare and endangeredbreeds of chickens, it is necessary that the cryobankstore individual ejaculates.In Russia, studies in this direction are being conducted atthe L.K. Ernst Federal Science Center for Animal Husbandryand its branch, the Russian Research Institute of Farm AnimalGenetics and Breeding Technologies. Many scientific publications describe differentprotocols for cryopreservation of semen of domesticatedand wild bird species. Technologies differ in the type ofcryoprotectant, the method of packaging ,the speed of freezing and thawing (fast/slow) and temperatureregimes. The effectiveness of the protocols can be assessedby analyzing the semen functional state in the laboratory and assessing the fertilizing capacity ofsperm in artificial insemination in vivo . It was found that highrates of avian semen freezing\u2013thawing were preferable in terms of improving its survival in contrast to the protocol formammalian semen . There is significant individual, intrabreed, and intraspecificvariation in bird semen cryostability, which demandsthat different cryopreservation strategies for different speciesand breeds be developed .Methods of semen quality assessment. Semen cryopreservationis very important for ex situ management ofavian genetic diversity, but the use of this method is limiteddue to the high variability of success rates. To calculate thenumber of sperm doses in the formation of the cryobank, it isnecessary to predict the fertilizing capacity of cryopreservedsemen. Unfortunately, in determining the effectiveness of theirdevelopment, many researchers are limited only to the assessmentof sperm motility. This test is not informative enough interms of predicting the fertilizing capacity of semen.A more effective prognosis for the fertilizing capacity ofthe semen is provided by assessment of morphological disordersincluding fluorescent staining of living and dead cells,flow cytometry, and evaluation of spermatozoon motilityparameters using computer-assisted sperm analysis (CASA).The CASA system permits one to estimate the percentage ofviable and morphologically normal cells (PVN), mass mobility(MMOT) and various parameters of movement, includingthe percentageof motile sperm (PMOT) and biophysical tests(resistance to osmotic stress (OSM), membrane permeability(FLUID)) .However, the set of these tests does not fully reflect the functionalityof semen.The functional capacity of thawed semen can be reliablydetermined in vitro by analyzing the interaction of the spermwith the inner layer of the perivitelline layer of the egg yolk. In evaluation ofthe functional state of spermatozoa in vitro in the laboratory,it is advisable to use the perivitelline membrane of egg yolk.The assessment is based on the number of hydrolysis points(spermatozoon penetrations) per unit area of the inner perivitellinelayer . This method, comparedto traditional quality assessment, is more informative forpredicting the fertilizing capacity of semen.Preservation of female gametes. By now, no method hasbeen developed to preserve germ cells of female birds. Thepresence of large amounts of yolk in the eggs of birds hampersthe use of existing cryopreservation methods .This is a serious issue in the preservation of a breed/population,as it cannot be fully preserved without the genetic contributionof individuals of both sexes: there is a loss of maternalhereditary material, including the mitochondrial genome.Currently existing methods of preservation of reproductivecells of birds (semen) allow restoration of endangered breeds/populations only by grading.A relatively new technology is the transplantation ofcryopreserved gonad cells from neonatal chickens to adultrecipients for reproduction of donor offspring. This methodof transplantation can contribute to the conservation of endangeredbird species and maintain their genetic variability. Cryopreservation of ovarian tissue isactually the only effective way to preserve in vitro female germplasma in birds. A method of vitrification of donor ovarian tissues in straw is proposed. Ovarian tissue fragments from1-week old females are transferred to a metal rod, then vitrifiedin liquid nitrogen using special media. By this method, theovarian tissue of birds can be stored and transported. Successfultransplant survival was demonstrated by Liu et al. (2012).In addition, ovarian transplantation can be used for research ingenetics and developmental biology . Since this technique involves significantsurgery and requires the use of immunosuppressants, today itappears to be costly and technologically challenging in routineimplementation.Preservation of embryonic cells. Chicken primary germcells (PGCs) can be isolated and cultured in vitro. PGCs actas a valuable source material for cellular genetic engineering,germ plasm production, and genetic conservation of speciesand populations . Indeed, bird PGCs canbe reproduced in culture and conserved without irreversiblealteration of their biological properties . Two mainmethods are commonly used for cryopreservation of PGCsin birds: slow freezing (SLF) and ultrafast freezing (Vitrif). These cells can be used to repair gonadaltissues with germ cells of the donor line. This method is notcurrently applicable for the preservation of entire embryos. Both methods require further research, butwe can now definitely state that in the future this approachto in vitro preservation of cells will provide grounds for thedevelopment of a practical gene bank and systematic genomicbank for birds.It has been established that semen cryostability is a geneticallydetermined trait , but the mechanismsof the effect of cryopreservation on the epigenetic state of cellshave not yet been fully investigated. Semen freezing\u2013thawingcan injure genes, including SNORD116/PWSAS and UBE3A,associated with fertility .The study of changes in boar semen after cryopreservationrevealed differences in 41 proteins . ProteinsSOD1, TPI1, ODF2, and AKAP3 have been proposedas markers affecting semen resistance to freezing. In Gallusgallus domesticus, ontology genes were found for SOD1,TPI1, and ODF2. Consider these genes in more detail. Theprotein encoded by the SOD1 gene (Superoxide dismutase 1)binds copper and zinc ions and promotes the breakdown ofsuperoxide radicals into molecular oxygen and hydrogenperoxide . Another isozyme ofthis protein is found in mitochondria, and its functions havenot yet been studied. The enzyme TPI1 (Triosephosphateisomerase 1), which consists of two identical proteins, catalyzesthe isomerization of glyceraldehyde 3-phosphate (G3P)and dihydroxyacetone phosphate (DHAP) in glycolysis andgluconeogenesis .It has been found that HSP90 (Heat shock protein 90)proteins are associated with sperm motility, and their pooldecreases significantly after freezing\u2013thawing .Significant protein changes in human sperm before and aftercryopreservation were detected by Wang et al. (2014): mitochondrial matrix proteins ACO2 (Aconitase 2) and OXCT1(3-oxoacid CoA-transferase 1); filamentous protein TEKT1(Tektin 1), which is necessary for the formation of ciliary andflagellar microtubules; glycolytic enzyme ENO1 (Enolase 1),the intermediate filament protein vimentin; and the amino acidtyrosine. These molecules are associated with sperm motility,viability, and acrosome integrity .As a result of semen freeze\u2013thawing, the amounts of antioxidantproteins such as SOD1, PRDX6 (Peroxiredoxin 6),TXNDC2 (Thioredoxin containing domain 2), GSTM3 (Glutathione-S-transferase mu 3), membrane proteins CYB5R2(Cytochrome b5 reductase 2), pellucid zone proteins ZPBP1and ZPBP2 (Zona pellucida binding protein), acrosomal proteinsACRBP (Acrosin binding protein), and SPACA3 (Spermacrosome associated 3) were found to decrease. Simultaneously,the amounts of other proteins whose accumulation isobserved in cells under stress \u2013 ANX1, ANX3, and ANX4 (AnnexinA); clusterin (CLU Clusterin); importin-1b (KPNB1);Karyopherin subunit beta 1, HIST1H4A (Histone cluster 1 H4family member a); TUBA1A ; and SPAG17(Sperm associated antigen 17) increased .A study of the effect of cryopreservation on Gallus gallusdomesticus spermatozoa has shown an increase in the amountsof 36 proteins and a decrease in 19 proteins after thawing.These proteins are linked to spermatozoa metabolism . Proteins such as ACRBP, FN1 (Fibronectin 1),HSP90AA1 (Heat shock protein 90), and VDAC2 (Voltagedependent anion channel 2) are biomarkers that predicttolerance of cryopreservation in boar semen .During fertilization, spermatozoa deliver the paternalmRNA to the egg and thus play an important role in the earlydevelopment of the embryo. During freezing, transcripts andmRNA\u2013protein interactions in spermatozoa may be lost, whichmay affect embryo development . Correlationsbetween sperm mRNA and early embryo developmentin humans and some animals were identified in . Studies by Valcarce et al. (2013) showed a decreasein the expression of the PRM1, PRM2, PEG1/MEST, andADD1 genes associated with human sperm fertility after cryopreservation.Some studies confirmed changes in transcriptsof some proteins and micro-RNA. Attempts are being madeto explain some epigenetic modifications that may occur inspermatozoa during freezing .Cryopreservation of semen is a very important method ofassisted reproduction, but the freezing\u2013thawing procedureis harmful, because it leads to a decrease in the motility andviability of spermatozoa, premature capacitation, and, as aconsequence, poorer effectiveness of artificial fertilization.Therefore, the addition of some proteins normalizes the processof condensation and accelerates fertilization in vitro. Forexample, use of TrxA-FNIIx4-His6 is a promising biotechnologicalapproach for cryopreservation of ram semen andmaintenance of spermatozoon viability .In addition to preserving genetic material by creating asperm bank, it is possible to create a cryobank of embryos. Incattle, the effect of resveratrol on embryos after cryopreservationwas evaluated. Its effects on mitochondrial functionpreservation, DNA integrity, SIRT1 (Sirtuin 1) expression and embryo development ability have been studied. Embryosurvival was significantly improved when embryos were incubatedin a medium containing 0.5 \u03bcM of resveratrol afterthawing. Besides, SIRT1 expression and cell-free mtDNAcontent in the medium were higher in the case of embryostreated with resveratrol. It should be noted that slow freezingaffects mitochondrial integrity and function in blastocysts. It is important to improve in vitromaturation (IVM) conditions for immature oocytes aftercryopreservation, especially if a limited number of oocytesare collected from specific donors. Culture systems with freshoocytes significantly accelerate the meiotic development ofvitrified oocytes and significantly increase the rate of blastocystformation after parthenogenetic activation and transferof somatic cell nuclei .The understanding of the molecular mechanisms that determineepigenetic processes occurring in reproductive cellsduring freezing\u2013thawing will improve the effectiveness of thetechnologies used to preserve species, breeds, and populationsof rare and endangered animals and birds.The preservation of semen by freeze-drying is an innovativemethod. The advantages of lyophilized semen are that it canbe (1) stored at 4 \u00b0C for a long time and (2) stored and transportedat room temperature without the use of liquid nitrogenor dry ice as cooling agents.It is expected that sperm lyophilization, rather than cryopreservation,can become a new simple method of preservinggenetic resources and be used, among other things, to producetransgenic animals . The state of research inthe field of freeze-drying of wild and domestic animal semenindicates an increasing interest in this method of preservinggenetic resources. Methods of lyophilization in relation tomicroorganisms and plant cells have been developed andsuccessfully applied. Interest in the lyophilization of reproductivecells, as a possibility of a cheaper way to preserveand transport (including space) genetic material of wild anddomestic animals, compared with cryopreservation, is growingrapidly in the world; research is underway in Japan, Israel,Egypt, Spain, and France. Methods of lyophilic drying aredeveloped with regard to species features. Promising resultshave been achieved in mice, rats, hamsters, cattle, sheep,rabbits, chimpanzees, giraffes, jaguars, etc., but it is tooearly to talk about the problem as solved, since the functionalcharacteristics of sperm are not fully preserved . The mainissues are associated with damage of the motility apparatus ofspermatozoa, membranes, and DNA. As for birds, includingpoultry, research on the freeze-drying of their semen has notbeen carried out, at least not published.Cryopreservation triggers damage processes not only at themechanical level of membrane damage, but also chemical andphysical processes of denaturation of proteins and lipids ofmembrane bilayers. These processes result in sublethal freezing and the launch of cryocapacitation, generation of reactiveoxygen species, and aberrations in sperm proteins, lipids, andsugars .It is well known that the tolerance of cold shock and cryostabilityin spermatozoa of different livestock species, includingfarm birds, varies greatly. Cryopreserved semen of anyanimal species has reduced fertility compared to fresh sperm.The causes of fertility loss include the susceptibility to coldshock, cooling rate, diluent composition, and osmotic stress.There are also factors that affect the functional state of frozen/thawed spermatozoa: membrane stability, oxidative damage,membrane receptor integrity, and nucleus structure . In the course of cryopreservationand thawing, sperm can experience both irreversible damage,expressed as the absence of motility and various morphologicaldisorders, and reversible, associated mainly with atemporary injury of the structure and membrane permeabilitydisturbance.It is believed that the high content of intracellular proteintogether with osmotic \u201cshrinkage\u201d of the sperm membraneassociated with the formation of extracellular ice leads tointracellular vitrification of sperm during cooling. At highcooling rates, sperm damage is the result of osmotic imbalanceoccurring during thawing, rather than intracellular iceformation during freezing. Osmotic imbalance occurs at highcooling rates due to limited diffusion of ice crystallization inthe extracellular fluid; that is, the amount of ice formed duringcooling is less than expected from the phase equilibrium diagram.A significant interbreeding variability in the cryostabilityof cock semen, estimated by the activity of thawed semen, isknown: the coefficient of variation (Cv ) can be up to 23\u201325 %.A greater individual variability in cock spermatozoon activityin the freeze/thaw cycle has been shown in . The coefficient of variation (Cv ) ofspermatozoon activity was 6.1 % in native sperm and 19.5 %in frozen/thawed, which points to a broad norm of spermresponse to low temperatures.The generally accepted parameters of ejaculate selectionfor cryopreservation are volume, concentration, and spermatozoonmotility. These criteria do not provide a complete predictionof the degree of reproductive cell, cryotolerance, which islargely due to the state of the membranes, as the membranesare first to be damaged in the freezing\u2013thawing process.One of the ways to assess the degree of cryopreservation ofspermatozoon membranes is staining with Sperm VitalStaindye , which allows assessmentof the degree of cryopreservation by changing the colorof damaged cells . Lipidfractions of membranes, such as glycolipids, phospholipids,sterols, cholesterol, the cholesterol/phospholipids ratio, etc.,affect the state of cell membranes; their permeability, microviscosity,and fluidity; molecular mobility of lipids in themembrane; the process of capacitation, the interaction of eggand spermatozoon membranes; and the result of fertilization.Recent studies of sperm cryostability have established theeffect of the amino acid profiles of seminal plasma in differentbreeds of chickens on DNA fragmentation . The composition of intracellular spermatozoonprotein has been found to be associated with indicators ofosmotic imbalance after thawing . Theresults of these studies open up new aspects of sperm cryobiology,which is a prerequisite for the development of newtechnologies for semen preservation, including vitrificationand lyophilization.Problems of early embryonic mortality. It is well knownthat the use of frozen/thawed semen reduces not only thepercentage of their fertility but also the viability of embryos.The mortality rate of embryos in the early stages of developmentcan reach 8\u201317 % .This research area is insufficiently studied, as it is technicallydifficult to investigate the causes of arrested development,since signs of early embryonic death are not determined.DNA damage is probably a major cause of early embryonicmortality caused by functional damage to sperm nuclearstructures . In addition,the influence of toxic endo/exocellular cryoprotectants usedin sperm freezing and their concentrations, which may alsocause embryo death at an early stage of development, shouldnot be ruled out .Thus, the genetic diversity of the preserved material is reducedat different stages of postsingamy due to the eliminationof individuals with reduced cryoresistance of reproductivecells.Cryoprotectants. A necessary condition for successfulcryopreservation of reproductive cells is the use of cryoprotectants.Cryoprotectants acting inside cells penetrate intocells and prevent the formation of intracellular ice, but athigh concentrations they exert a damaging effect. Exocellularcryoprotectants act outside the sperm in the extracellular spaceand protect cells by dehydrating the intracellular space andlimiting the action of osmotic shock during thawing.Glycerol, one of the best known cryoprotectants, is the mosteffective and less toxic to cock sperm, but unfortunately has acontraceptive effect after insemination of hens and requires removalbefore insemination. The most widely used penetratingcryoprotectants are dimethylsulfoxide, dimethylacetamide,dimethylformamide and ethyleneglycol. Semen samples canbe thawed without further processing, and high fertility levelsare obtained with these substances depending on the coolingrate and the type of semen packaging . Nonpenetrating cryoprotectants, also known as osmoprotectants,are low-molecular-weight hydrophilic nontoxicmolecules that stabilize internal solutes under osmotic stressin cells. These cryoprotectants are often used in combinationwith penetrators .Recent approaches to the development of cryoprotectantsof fundamentally different actions are based on antifreezeglycoproteins (AFGP) and antifreeze proteins (AFP), foundin the blood and tissues of poikilothermic organisms living infreezing environments (insects and marine fish). The obtainedsubstances inhibit the growth of ice crystals in a noncolligativemanner. The use of AFP opens up a promising direction for cryopreservation of living tissues and cells. The efficacyof some fish AFP or fish AFGP against hypothermic damagehas been reported while preserving swine and cattle oocytes,whole rat liver, and model membranes. To preserve sperm,attempts have been made to develop cryopreservation methodswith the addition of fish AFP in different species with differentefficiencies. AFP and AFGP of marine fish have recentlybeen found to improve buffalo sperm cryopreservation results.There are studies on the use of recombinant AFP-basedDendroides canadensis (DAFP) larvae for cryopreservation.Addition of DAFP to the diluent protects buffalo semen during freezing\u2013thawing and increases thefertility of cryopreserved semen .Collections of genetic banks are of paramount importance inpreventing the extinction of breeds due to extreme geneticconditions, such as small breed/population size and highincidence of genetic defects as a result of intensive breedingand genetic drift. Stored material from animals that do notcarry undesired or lethal mutations can be used to reduce thefrequency of defects to an acceptable level.Biobanks are a ready-to-use source of genetically diverseand specialized DNA. Conserved materials are used in studyinggenetic diversity, genomic associations, gene functions,and other issues. Importantly, over time, genetic banks canprovide samples from different generations, which contributesto the accuracy of genomic selection. These advantages will beeasier to implement if the information is catalogued taking intoaccount the phenotype and genotype and the stored sampleshave genomic certificates .The problem of in vitro preservation of genetic diversity,including farm birds, is being solved in many countries of theworld. One of the advantages of preserving genetic diversityin vitro in cryobanks is the economic component .Recently, a new approach to interaction between organizationspreserving the gene pool ex situ in vivo and ex situ in vitrohas been developed. The goal of the genetic bank is not onlyto obtain and preserve reserve biological material but also toclosely cooperate with collections in live breeding to expandgenetic diversity while preserving ex situ in vivo.Genetic banks for the conservation of farm birds can takeinto account the experience of the European Union, theEuropean Federation of Animal Science (EAAP), and FAO,which have established European and international consultativeforums to discuss and take practical measures for theconservation of genetic resources worldwide. However, theimplementation of this idea is a complex process, whichrequires interdisciplinary cooperation and clear definition ofgoals .The legislation of the Russian Federation provides for aregulatory framework (Strategy) for the conservation of rareand endangered species of animals, plants and fungi (OrderNo. 212-r of the Government of the Russian Federation of17.02.2014), including preservation in vitro. 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These have now been corrected in the article.In \u201cPredicting the Impact of Describing New Species on Phylogenetic Patterns\u201d ["} +{"text": "Scientific Reports 10.1038/s41598-019-52314-2, published online 06 November 2019Correction to: Gustavo F. Trindade was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:A.A. and R.P.-G. envisaged the work to use biodegradable and biocompatible polymers recently described by our group to be used as stabilizer of gold nanoparticles for potential biomedical devices. B.B., R.A.-V. and G.M. scaled up the synthesis to obtain enough amounts of polymers with minor changes considering the previous published synthesis, while A.J.-R. prepared and tested the stability of the AuNP systems to collect data to difference among the metallic nanoparticles, Y.H. designed, fulfilled and characterized all the parameters necessary for the inkjet printing strategy. G.F.T. characterized and analyzed the printed specimen through ToF-SIMS. M.-J.S. carried out the TEM microscopy characterization. B.B. and A.J.-R. were primarily in charge of compiling all the experimental data to write the manuscript. Besides, A.A., Y.H., R.W., M.-J.S. and R.P.-G. proofread it.The Acknowledgements section now reads:This work was supported by the Engineering and Physical Sciences Research Council , by the Spanish Ministerio de Econom\u00eda y Competitividad MinECo, (Grants Nos. CTQ2016-78703-P and MAT2016-78703-P), by the Junta de Andaluc\u00eda and the University of Seville (V y VI Plan Propio PP2016-5937 and OTRI 2010/00000762). The European Union through the CT-2011-1-REGPOT285895 AL-NANOFUN project for the microscopy facilities sited in Seville is also gratefully acknowledged. Authors would like to thank the Functional Characterization and NMR Services from CITIUS, University of Seville, for the support offered to develop this work and Dr. Manuel Pern\u00eda for reviewing the draft."} +{"text": "Scientific Reports 10.1038/s41598-019-53830-x, published online 26 November 2019Correction to: Jay-How Yang was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:K.E.R. performed most of the work; C.D.T. performed the negative stain with input from P.C.; J.Y.H. performed initial negative stain screening; F.M.C. developed the small scale screen and performed most of the cloning; K.E.R. and D.T.H. wrote the paper with input from P.F.; D.T.H. and P.F. directed the study."} +{"text": "August 26, 2019, the author contributions were incomplete. It should be listed that Stephanie E. Vargas Abonce and M\u00e9lanie Leboeuf contributed equally to this work. This correction does not affect the conclusions of the paper. The equal contributions of S.E.V.A. and M.L. have been corrected online.In the article \u201cHomeoprotein Neuroprotection of Embryonic Neuronal Cells,\u201d by Stephanie E. Vargas Abonce, M\u00e9lanie Leboeuf, Alain Prochiantz, and Kenneth L. Moya, which published online on"} +{"text": "Scientific Reports 10.1038/s41598-020-66409-8, published online 25 June 2020Correction to:Giselle Melendez was omitted from the author list in the original version of this Article. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:2O3, SiO2, TiO2, and WO3 thin films. U.K. took AFM images, collected in-situ SE data and designed the dynamic dual box model for in-situ SE data analysis. A.M. and G.M. contributed to the SE data analysis. S.V. and U.K. performed XRD analysis. S.G. and U.K. performed XPS analysis. N.I. and M.L. made contributions to the discussions over the experimental results. The manuscript was edited and approved by all authors. E.S. and M.S. supervised the project.U.K. and D.S. performed ALD depositions of Al"} +{"text": "Polyalthiopsis Chaowasku (Annonaceae) was a poorly known monotypic genus from Vietnam that was recently segregated from the highly polyphyletic genus Polyalthia s.l. The sister clade relationship between Polyalthiopsis and Miliusa was not well established in previous study. The phylogenetic position of two Polyalthia spp. from China, P.chinensis S.K.Wu ex P.T.Li and P.verrucipes C.Y.Wu ex P.T.Li, remains unresolved and is shown here to be phylogenetically affiliated with Polyalthiopsis. Phylogenetic analyses of six chloroplast regions unambiguously placed Polyalthiachinensis and P.verrucipes in the same clade with Polyalthiopsisfloribunda ; the entire clade is sister to Miliusa with weak to strong support . Polyalthiachinensis and P.verrucipes share several diagnostic characters with Polyalthiopsisfloribunda, including the raised midrib on the upper surface of the leaf in vivo, conspicuous foliar glands when dried, petiole with transverse striations when dried and axillary inflorescences. The two species differ from Polyalthiopsisfloribunda in having fewer flowers per inflorescence, longer linear petals and two ovules per carpel. On the basis of the combined molecular phylogenetic and morphological data, we propose two new combinations, Polyalthiopsischinensis (S.K.Wu ex P.T.Li) B.Xue & Y.H.Tan and Polyalthiopsisverrucipes (C.Y.Wu ex P.T.Li) B.Xue & Y.H.Tan. The protologue of Polyalthiaverrucipes did not include a description of the flowers, which we provide here. An updated description for the genus Polyalthiopsis and a key to species in the genus Polyalthiopsis is also provided.The genus Polyalthia Blume has historically been the source of considerable taxonomic confusion in Annonaceae due to its highly polyphyletic status Hook. f. & Thomson . The species was first collected in 1924 and described under the name Polyalthiafloribunda Jovet-Ast as sister to Miliusa, leading Polyalthiopsis Chaowasku, to accommodate it. With only one Polyalthiopsis species and limited DNA regions used in the phylogenetic study, the sister relationship between Polyalthiopsis and Miliusa was not well established. It is also difficult to identify important diagnostic characters for Polyalthiopsis with only one flowering collection and a single monocarp available for taxonomic comparison.Amongst the newly segregated genera, Vietnam . The typovet-Ast . I.M. TuPolyalthia and await assignment to specific genera from M\u00eadog, Xizang, China, in 1974 . Until now, the species was only represented by these two collections.The name in 1974 . A seconPolyalthiaverrucipes was published in 1976, based on a fruiting collection from Menghai, Yunnan, China, in 1936 . Although S. K. Wu 1345, 1375, KUN; X. L. Hou 112, CANT, IBSC; and T. X. Sun 200037, CANT), we failed to locate those specimens in the cited herbaria.The name in 1936 . A seconP.chinensis lacking fruiting specimens and P.verrucipes lacking flowering specimens, rendering morphological comparison problematic. Based on the foliar glands and leaf venation, P.chinensis as synonymous with P.verrucipes, although this treatment was rejected by Flora of China without explanation. P.verrucipes and P.chinensis, but with no clear indication of the source of this information, casting some doubt over the floral description of P.verrucipes.The relationship between these two species has been controversial. Both species are represented by very few collections, with P.verrucipes and the limited material available, the relationship between P.chinensis and P.verrucipes and their taxonomic placement has never been resolved. We therefore, carried out several field explorations to search for these two species. This resulted in new collections of Polyalthiaverrucipes, including flowers, enabling clarification of the relationship between P.chinensis and P.verrucipes, as well as their phylogenetic position. As a consequence, we were able to enlarge the poorly known genus Polyalthiopsis, supplementing available descriptions and providing better support for its sister relationship.With limited morphological characters, especially the lack of flowers in Polyalthiachinensis , as well as two accessions of Polyalthiaverrucipes were sampled and integrated with data of 56 Annonaceae accessions from previous datasets . For Miliuseae, representatives of all currently accepted genera were included.Two accessions of datasets , 2018. TmatK, ndhF, rbcL, psbA-trnH and trnL-F and ycf1) were sequenced for the above-mentioned four collections of Polyalthiachinensis and P.verrucipes. The samples, localities and GenBank accession numbers are listed in Appendix I.Six chloroplast DNA regions (CTAB) method analyses of the seven combined regions were conducted using PAUP ver. 4.0b10 (TBR) branch swapping with no limit to the number of trees saved. Bootstrap support (BS) was calculated following TBR branch swapping and no more than 10 trees saved per replicate.Maximum parsimony analyses were run. Each search used three incrementally heated and one cold Markov chain and was run for 10 million generations and sampled every 1,000th generation. The temperature parameter was set to 0.08. The mean branch length prior was set from the default mean (0.1) to 0.01 ) to reduce the likelihood of stochastic entrapment in local tree length optima (ESS) for each parameter (ESS > 200) were reached. The first 25% of samples were discarded as burn-in and the post-burn-in samples summarised as a 50% majority-rule consensus tree.Bayesian analysis was performed using NSF Extreme Science & Engineering Discovery Environment (XSEDE) application of MrBayes ver. 3.2.2 providedh optima . Convergh optima was usedComparative morphological data were obtained from specimens deposited in KUN, IBSC and PE herbaria and from published literature. Field surveys were carried out in Menghai County, Yunnan Province, with voucher specimens deposited in HITBC and IBSC.MP heuristic search retrieved four equally most parsimonious trees of 3,519 steps .The concatenated alignment of the 60-terminal dataset consisted of 7,334 characters. The MP and Bayesian analyses resulted in similar topologies. The 50% majority-rule consensus tree resulting from the Bayesian analyses under the six partitioned model is shown as Fig. The Polyalthiachinensis and P.verrucipes are not retrieved in the same clade as Polyalthiajohnsonii, but were strongly supported as members of the same clade as Polyalthiopsisfloribunda , with the entire clade sister to Miliusa with weak to strong support .Polyalthiachinensis was regarded as a synonym of P.verrucipes by Polyalthiaverrucipes, ) ) Fig. . Our fiePolyalthiachinensis have 1\u20132 flowers narrower than that of P.verrucipes (2.5\u20135 cm) and slightly thinner. The morphological data are therefore congruent with the phylogenetic topology and our phylogenetic and morphological analyses support the hypothesis that both species are not conspecific, as suggested by Although these two species resemble each other vegetatively Fig. , they diers Fig. , whereaswer Figs , 3F, G. re green , whereasite Fig. . The leaPolyalthiopsis Chaowasku was published in 2018, based on Polyalthiafloribunda collected in Vietnam , but strong support in the Bayesian analysis (PP = 1). This sister relationship was also well supported in BS = 86%, suppl. material 1: fig. S1). The relationship between Huberantha and the Polyalthiopsis-Miliusa collective clade is, however, not retrieved in this study. The long-recognised sister relationship between Miliusa and Huberantha in previous studies , with multiple transverse striations on the dried petiole per inflorescence per inflorescence. The shape of the petal also differs: the petals of Polyalthiachinensis and P.verrucipes are linear . The collective clade is strongly supported as sister to Polyalthiaverrucipes . The whole clade (comprising the three species) is weakly to strongly supported as sister to Miliusa. The morphological and molecular phylogenetic data therefore support the transfer of Polyalthiaverrucipes and P.chinensis to Polyalthiopsis and the new nomenclatural combinations are proposed here.The present phylogenetic study shows that Polyalthiaverrucipes was published based on fruiting material only Chaowasku \u2013 Polyalthiafloribunda Jovet-Ast, Notul. Syst. 9: 75. 1940. \u2013 Huberanthafloribunda (Jovet-Ast) I.M.Turner, Webbia 71: 229. 2016. \u2013 Type: Vietnam. Phanrang Prov., Tra Ca, 10 March 1924, Poilane 10052 , in flower.Medium-sized to large trees. Young twigs glabrous. Leaves petiolate, blade elliptic, with glandular dots observable when dry, base cuneate, apex acute to bluntly (caudate-)acuminate; petiole with transverse striations when dry; upper surface of midrib raised in living plants, becoming slightly sunken when dry, lower surface of midrib raised; secondary veins rather faint in living plants, becoming slightly raised on both sides when dry, leaf venation brochidodromous; tertiary veins reticulate. Flower(s) in 1- to 5-flowered inflorescences, bisexual, pedicellate; inflorescences axillary, peduncle inconspicuous, bracts present. Sepals broadly ovate-triangular. Petals membranous-papyraceous to leathery. Outer petals elliptic-ovate or linear-lanceolate. Inner petals (narrowly) elliptic-ovate or linear-lanceolate. Stamens numerous per flower, connective truncate, covering thecae. Carpels numerous per flower; ovaries with 1 or more line(s) of hairs; stigma terete; ovule(s) 1 or 2 per ovary, sub-basal or lateral. Monocarps oblong to rhomboidal or cylindrical, stipitate, glabrous. Seed(s) 1or 2 per monocarp, cylindrical, surface smooth, raphe broadly sunken and partially slightly raised in middle, endosperm ruminations lamelliform.Three species, known from Xizang, Yunnan Provinces of China and Th\u1eeba Thi\u00ean-Hu, Ninh Thu\u1eadn Provinces of Vietnam Fig. .Taxon classificationPlantaeMagnolialesAnnonaceae(S.K.Wu ex P.T.Li) B.Xue & Y.H.Tancomb. nov.B6164F55-50B2-53DF-9D9D-E7AC47339DDFurn:lsid:ipni.org:names:77209705-1Polyalthiachinensis S.K.Wu & P.T.Li in Acta Phytotax. Sin. 14 (1): 108, t. 4. 1976. BasionymQinghai-Xizang Exped. 74-4451 .China. Xizang: M\u00eadog, 20 Auguest 1974, Known from M\u00eadog in Xingzang Province Fig. , growingFlowering in August.B. S. Li & S. Z. Cheng 2668 (PE).DD . This spTaxon classificationPlantaeMagnolialesAnnonaceae(C.Y.Wu ex P.T.Li) B.Xue & Y.H.Tancomb. nov.682DD7C5-A379-546E-909A-FCE806978D83urn:lsid:ipni.org:names:77209706-1Polyalthiaverrucipes C.Y.Wu ex P.T.Li in Acta Phytotax. Sin. 14 (1): 110. 1976. BasionymLectotype (designated here). China. Yunnan: Menghai, July 1936, C. W. Wang 76321 .Trees to 15 m tall Fig. . BrancheKnown from several localities in Yunnan Province Fig. : Hei-lonFlowering in February to March; fruiting from April to July.Yunnan Exped. 9527 ; Man-xi, Menghai, 16 March 2016, Y.H. Tan MH1603 ; 5 March 2019, B. Xue & H.B. Ding 311, 312, 313 .China. Yunnan: Kun-man, Xiao-meng-yang, 27 April 1957, Polyalthiopsisverrucipes was assessed as EN A2c by the P.verrucipes was only represented in herbaria by two collections from Yunnan, China . Our field survey in 2016 identified one population with dozens of individuals of dbh ca. 10 cm and dozens of young treelets in Manxi village, Menghai County. We made a second visit to the location in 2019 and found only a few individuals with dbh larger than 10 cm and few treelets. Herbicide had been used in that location. The bark at the bottoms of the tree trunks was damaged. The local farmers appear to clear the forests in this way for tea plantation and it is anticipated that the trees with damaged bark could not survive. We hope additional undocumented sub-populations will be found and protected, although further field investigation is needed to better understand the current status of populations. At present, we recommend that this species be regarded as critically endangered (CR) based on current IUCN Red List Categories and Criteria (i) . PolyaltCriteria ."} +{"text": "Methylotrophic yeasts have been used as the platform for expression of heterologous proteins since the1980\u2019s. They are highly productive and allow producing eukaryotic proteins with an acceptable glycosylation level.The first Pichia pastoris-based system for expression of recombinant protein was developed on the basis of the treeexudate-derived strain obtained in the US southwest. Being distributed free of charge for scientific purposes, this systemhas become popular around the world. As methylotrophic yeasts were classified in accordance with biomolecularmarkers, strains used for production of recombinant protein were reclassified as Komagataella phaffii. Although patentlegislation suggests free access to these yeasts, they have been distributed on a contract basis. Whereas their statusfor commercial use is undetermined, the search for alternative stains for expression of recombinant protein continues.Strains of other species of methylotrophic yeasts have been adapted, among which the genus Ogataea representativesprevail. Despite the phylogenetic gap between the genus Ogataea and the genus Komagataella representatives,it turned out possible to use classic vectors and promoters for expression of recombinant protein in all cases. Thereexist expression systems based on other strains of the genus Komagataella as well as the genus Candida. The potentialof these microorganisms for genetic engineering is far from exhausted. Both improvement of existing expression systemsand development of new ones on the basis of strains obtained from nature are advantageous. Historically, strainsobtained on the southwest of the USA were used as expression systems up to 2009. Currently, expression systemsbased on strains obtained in Thailand are gaining popularity. Since this group of microorganisms is widely representedaround the world both in nature and in urban environments, it may reasonably be expected that new expression systemsfor recombinant proteins based on strains obtained in other regions of the globe will appear. Therequirementthat all C\u2013C bonds are formed enzymaticallyduring cellular metabolism poses a challenge for the cell. Onlysome microorganisms are capable of doing so, such as Gramnegativeproteobacteria and Gram-positive bacteria , as well as yeasts , which employmetabolic pathways for methanol oxidation to produceenergy and form C\u2013C bonds. Both in yeasts and bacteria,C\u2013C bonds are formed through the formation of formaldehyde, a toxic intermediate product that subsequentlyis either dissimilated into COMethylotrophic yeasts were discovered in the late 1960s,when methylotrophic bacteria had already been well known.The difference in times of their discovery was mainly causedby the challenges related to yeast isolation and significantbacterial contamination of samples . The habitats of methylotrophic yeasts are those wherethe biomass is degraded to give rise to methoxy groups . Methanol is produced naturallyduring methane oxidation and pectin or lignin degradation. Mostnatural isolates of methylotrophic yeasts were detected in treesap (exudates) or rotting wood .The interest in methylotrophic organisms for bioengineeringapplications arose in the early 1970s, when methanol wasan inexpensive raw material and was considered a virtuallyinexhaustible fossil feedstock. However, after the 1973 oilcrisis its price never dropped back to the pre-crisis level,and Western countries chose to lower their dependence onhydrocarbons. Plant-based proteins (and soybean protein inparticular) came to fore and replaces fodder protein derivedfrom unicellular methylotrophs.In the 1980s, methylotrophic yeasts became widely usedagain, although in new areas. Today, they are utilized as a platformfor genetic engineering and commercial-scale productionof recombinant proteins. Furthermore, methylotrophic yeastsare a convenient object for studying the features of eukaryoticcell organization. Methods for utilizing methylotrophic yeastsin applied areas are currently being elaborated .Pichia pastoris (Komagataella phaffii) is a methylotrophicyeast species that is most frequently used for scientific researchand commercial purposes. These yeasts can consume both sugars and methanol to produce proteins with a highyield. Initially, back in the 1970s, Phillips Petroleum suggestedusing P. pastoris as a single-cell protein producerdue to their ability to form high-density cultures both onglucose and methanol substrates .The maximum cell density achieved during fermentation ishigher than 100 g/L (dry basis) . In the 1980s,the P. pastoris-based heterologous expression system wasdeveloped with the use of a strong and strictly-regulatedalcohol oxidase 1 (AOX1) promoter . Incombination with the existing fermentation technologies foranimal feed protein manufacturing, AOX1 promoter was ensuringan exceptionally high recombinant proteins expressionlevel. An important benefit of using it in recombinant proteinmanufacturing is the high expression level in the presence ofmethanol and robust inhibition of the process in the absenceof methanol, which makes it possible to regulate the productionof target proteins, including the autotoxic ones . Production of biomass-derived hydroxynitrilelyase enzyme (the yield being 20 g of recombinant proteinper liter of the culture) was one of the first large-scale commercialmanufacturing processes established in the 1990s.Another advantage of P. pastoris is that it ensures the lowglycosylation level. Thus, the S. cerevisae yeast species isno longer used in production of recombinant proteins, sinceit often hyperglycosylates proteins (up to their completeinactivation) .The P. pastoris-based expression system has becomewidely used in basic research. Among methylotrophicyeasts, the P. pastoris species was the first to be developed.It turned out to be a convenient bioengineering system forproduction of eukaryotic proteins that are not properlyexpressed in bacteria. Phillips Petroleum made a forwardlookingdecision to make this expression system available tothe scientific community for research purposes, which wasa major driver for common application of this yeast speciesas a platform for recombinant protein expression. Histidineauxotrophicstrain GS115, reconstituted prototrophic strainX-33, aox1 knockout strains KM71 and KM71H, as well asprotease-deficient strains SMD1168 and SMD1168H, andade2 auxotrophic PichiaPink\u2122 strain, are the most frequentlyutilized commercially available strains. However, their usefor commercial purposes is restricted by material distributionpolicy. Therefore, searching for alternative options thatcould be used instead of the licensed P. pastoris strains isquite relevant today.Progress in molecular biology methods as well as mountingevidence on gene sequences for various species made it possibleto investigate into phylogeny of methylotrophic yeasts,which was accompanied by a number of surprises.First of all, gene sequence analysis revealed that yeastsknown as Pichia are not monophyletic despite the phenotypicsimilarity of the majority of species of this genus.First research works discovered that methanol-assimilatingspecies P. pastoris, P. angusta and Hansenula polymorphaare remotely related with one another as well as with Pichiamembranifaciens, the typical Pichia species. Yamada et al. suggested assigning P. pastoris to a new genusKomagataella and classifying P. angusta as Ogataea polymorphainto a freshly described genus Ogataea. New generawere suggested on the basis of analysis of divergence in partiallarge subunit (LSU) and small subunit (SSU) ribosomalRNA (rRNA) sequences. Since each analysis was limited to arelatively small number of species, it was unclear how closeP. pastoris and P. angusta (H. polymorpha) were related tonumerous unstudied species, and therefore suggestions werenot accepted . However, further analysis ofD1/D2 regions in the LSU of the rRNA gene sequences forall now-known ascomycetes confirmed that the Komagataella,Ogataea and Pichia classification is correct , while phylogenetic divergence demonstratedas a result of single-gene sequence analysis was confirmedduring the analysis of multi-gene sequences . Therefore, Komagataella, Ogataea and Pichia arethree separate genera. Thus, Komagataella pastoris is the mostcorrect name from the viewpoint of taxonomy. However, dueto historical reasons, P. pastoris remains most wide-spreadtoday.Secondly, it turned out that the name P. pastoris coversat least two yeast species, i. e. Komagataella phaffii andK. pastoris. The genesequence analysis also revealed that these are not the onlyKomagataella representatives. K. pseudopastoris initiallydescribed as P. pseudopastoris wasalso classified as part of Komagataella on the basis of LSUand SSU rRNA sequence analysis. Similarly, K. phaffii wasclassified as Komagataella on the basis of the analysis of theD1/D2 fragment in the LSU rRNA gene .Evolution of parallel sequencing methods helped to buildup the database on genome sequences of a great number ofmicroorganisms (including methylotrophic yeasts), whichallows for a more detailed phylogenetic analysis. 18S rRNAgene sequence is the most wide-spread and conservativemarker for analysis of phylogenetic relations among variousfungi representatives. Relevant genes were extracted fromgenomes of methylotrophic yeasts part of the NCBI databaseand used for the phylogenetic tree design .Nucleotide sequences were evened with the help of MAFFTalgorithm in MAFFT v7.312 program with \u2013localpair and \u2013maxiterate 1,000 parameters.Phylogenetic tree was designed on the basis of the maximumlikelihood method with the help of IQ-TREE program . \u2013Auto and +R (FreeRate heterogeneity)parameters were used to determine the best patternsof nucleotide replacement models, minimum value of theAkaike criterion (AICc) being the key parameter. Two ratios,i. e. SH-like aLRT and ultrafast bootstrap, were used for statistical supportof maximum likelihood in the IQ-TREE program.As one can see, methylotrophic yeast used for production ofrecombinant proteins split into three groups: Pichia, Ogataeaand Komagataella . Also, one can derive at aconclusion that Ogataea is phylogenetically more heterogeneousin comparison to Pichia and Komagataella.P. pastoris (K. \u0440haffii and K. kurtzmanii ). The P. \u0440astorisyeasts group, the majority of representatives of which havebeen reclassified as Komagataella representatives, is mostwell-studied among methylotrophic yeasts. Its typical habitatis tree sap (exudate) in regions from moderate to tropical.Initially, P. pastoris was isolated from chestnut exudates inFrance. Later, it was discovered to occur widely in Hungaryand USA . Besides, P. pastoris yeasts were discoveredin exudates of oil palm in Nigeria , sap ofwhite algarrobo in Argentina , and sapof red oak in Canada . The zoningof their occurrence is very curious: this is a predominantspecies of methylotrophic yeasts in the woods of the Pacificcoast of the American Northwest; they are present in Europe, Africa and South America, andare completely missing in Japan .Although the P. pastoris-based expression system patentedby Philips Petroleum is wide-spread, alternative strains of methylotrophic yeasts are being searched for. Those are requiredfor invention of new unlicensed and thus applicablefor commercial use platforms for recombinant proteins production.P. pastoris (K. phaffii) CBS7435 strain is the closest tothose previously suggested by Philips Petroleum. Strainsderived from it are unlicensed . At thesame time, this strain is a predecessor of patented strains mostwidely used for production of recombinant proteins thesedays. On the one hand, this paves the way for use of CBS7435compounds thanks to the vast knowledge base built up withtheir help, and on the other hand, not all genome modificationsfor this strain can be patented taking into considerationtheir description in academic literature and in patents.Strain K. kurtzmanii Y-727/KPB 2878/Starmer 75-208.2/CBS 12817/NRRL Y-63667 was patented in the RussianFederation.It was isolated by Prof. Starmer from fir sapin Arizona mountains, USA , and isone of the closest relatives of the P. pastoris (K. phaffii)CBS7435 strain.P. guilliermondii (Meyerozyma guilliermondii ). P. guilliermondiisporogenous species can be isolated from a varietyof sources, i. e. plants, lake water, cow rumen, or oilcontaminatedsoil. Besides, these yeasts were discoveredin elm-dwelling insects, in uncontaminated oil and water, in shrimp and other invertebrates,and in low-salinity sea water . Before,this yeast species was used in gene engineering as a source ofgenes that were among other things expressed in P. pastoris, rather thanas an expression system.Since the majority of methylotrophic yeasts have similarmethanol-inducible promoter in methanol utilization paths, the research group from Malaysiatested the assumption that expression constructs developedon the basis of K. phaffii could be used for expression of recombinantproteins in other methylotrophic yeasts . They isolated the strain called Pichia sp. strain SOfrom a rotten orange; its SSU sequence demonstrated its100 % similarity to P. guilliermondii. Then, authors discoveredthat zeocin can be used as a marker for strain SO , and conducted work on cloning the recombinantlipase expression construct. The work continued, and in 2017an article on optimization of expression of T1 lipase isolatedearlier from Geobacillus zalihae with use of P. guilliermondiiwas published. As the result of this work, T1 lipase yielded a3-fold increase over medium .P. (O.) methanolica was suggested by Invitrogen (USA)as a platform for production of recombinant proteins a littlelater than the same company suggested P. pastoris. Initially,it was isolated from soil sample in Japan in 1974; strains ofthis species were also isolated in the USA . In 2008, yeasts of this group (heterogeneousas P. pastoris) were also isolated on the territory ofRussia from willow galls created by slug . P. (O). methanolica didn\u2019t become popular as aplatform for production of recombinant proteins althoughthere are single messages about its use, e. g., for expression ofhuman glutamic acid decarboxylase .Probably, the popularity of P. (O). methanolica as a platform for recombinant proteins is low because Invitrogen has adifferent, P. pastoris-based platform (K. phaffii).Hansenula (O.) polymorpha is a thermotolerant methylotrophicyeast able to grow at temperatures below 50 \u00b0\u0421wide-spread in nature. Besides such media as rotting fruit andother plants typical for methylotrophic yeasts, one of typicalhabitats for H. polymorpha is organism of insects, includingDrosophila melanogaster typically used in research . Since H. polymorpha demonstratesgood growth at high temperatures, it could possibly be foundaround hot springs and in tropical areas.In science, these yeasts have been used as a model organismfor studying peroxisome biogenesis and degradationmechanisms, methanol metabolism control, assimilationof nitrates and reaction to stress .H. polymorpha turned out rather effective for production ofrecombinant proteins as well . Recombinantantigen of the hepatitis B virus (HBsAg), that was successfullycommercialized under HepaVax-Gene and AgB trademarks, is the most significant therapeuticprotein produced with the help of H. polymorpha. Producersof recombinant proteins with high potential for pharmaceuticalpurposes were developed on the basis of H. polymorpha:hirudin from leech Hirudinaria manillensis and some human proteins including \u03b11-antitrypsin, IFN\u03b1-2a , serumalbumin , epidermal growth factor and parathyroid hormone .Besides medical proteins, there were developed producersof food and commercial enzymes: hexose oxidases , phytases , levansucrasefrom Zymomonas mobilis , and glucoseoxydases from Aspergillus niger .P. (O.) thermomethanolica. Besides strains utilized byInvitrogen, there is O. thermomethanolica BCC16875 strainthat can be considered one of best-studied methylotrophicyeasts alternatives for production of recombinant proteins.Knowledge of occurrence of O. thermomethanolica isvery scarce as this yeast species was discovered only recently,in 2005, in soil samples in Thailand .For the first time, information about strain BCC16875was published by a research group from Thailand in 2012.The research focuses on testing the possibility of using biomoleculartools for accumulation of protein in this strain.Classical methanol-inducible alcohol oxidase (AOX1) promotersand constitutive glyceraldehyde 3-phosphate dehydrogenase(GAP) promoters utilized for working withP. pastoriswere shown to drive efficient gene expressionin this new strain. Recombinant phytase and xylanase wereexpressed from both promoters as secreted proteins, with theformer demonstrating different patterns of N-glycosylationdependent on the promoter and culture medium used. Themajor glycoprotein oligosaccharide species produced fromO. thermomethanolica BCC16875 is Man8-12GlcNAc2 thatis similar to that of other methylotrophs. Moreover, mannosylphosphateand \u03b1-1,6- and \u03b1-1,2-linked mannose modificationsof heterologous secreted protein were also detected. Thelevel of expression of recombinant protein turned out to beequal to the level of expression of commercial strains, which makes the suggested platform a good alternative to widelyused Invitrogen\u2019s strains .Studies of the suggested strain O. thermomethanolicaBCC16875 continued during next following years. Promoterstypical for this train were studied , as well as methods of highdensitycultivation for expression of recombinant proteins. Besides, work on optimization ofstrain\u2019s metabolism for increase of target products\u2019 outputwas started. Thus, the level of expression of auxiliary proteinsof endoplastic reticulum was increased for this purpose. Studies of the strain becameespecially active after 2016, and today there is a significantnumber of works on updating it to the present-day level as anexpression system. In 2018, the CRISPR-Cas9 system wasadapted for this strain ,a new sucrose-induction-based expression system was developed, andstudies of metabolism at proteomic and transcriptomic levelscontinued .Candida boidinii is the first described species of methylotrophicyeasts. It is also apparently most wide-spread innatural habitat . Mainly it\u2019s various plantsubstrates . These yeastsare also abundantly present in naturally fermented olives. Methylotrophic yeasts are also foundin cacti. Their spoiled parts happen to host both C. boidinii,and O. polymorpha, although these species do not prevailamong yeasts discovered in these yeast samples. In additionto regular occurrences of methylotrophic yeasts, \u0421. boidiniiis also an important marker of seashore contamination. Theirlines are predominant in many water and sand samples inBrazil .According to the phylogenetic tree of 18S rRNA genesequences presented in this review, C. boidinii could be classifiedas Ogataea . Up to 2009, C. boidiniiwas developed as a platform for production of recombinantproteins alternative to P. pastoris by a group of Japanesescientists . C. boidinii-based recombinantprotein expression system has some characteristicsthat can be useful in comparison to other methylotrophicyeasts. Level of expression in C. boidinii varies dependingon the source of carbon: AOD1 promoter demonstrates highlevel of expression in methanol-grown or methanol-glycerolgrowncells, medium level of expression in glycerol-growncells and zero expression in case glucose- or ethanol-growncells are used as source of carbon . The level of expression is significantlyhigher for C. boidinii than for O. polymorpha. Besides, highlevel of expression can be ensured in C. boidinii in case ofmethanol + glycerol medium, which allows shortening thetime for high-density cell cultivation. In case of P. pastoris,glycerol suppresses expression of methanol-induced genes,and therefore control over complete eating of glycerol in theculture prior to methanol induction is required. A strain withknocked-out vacuolar proteinase A (PEP4) and proteinase B(PRB1) is available for both P. pastoris and C. boidinii. During studies with use of C. boidiniigenes expression system, there were developed strains forproduction of toxic proteins, i. e. membrane-bound peroxisome allowing to cumulate toxic proteins , as well as effective secretionsystem for production of active transglutaminase .Yeasts are isolated from water, seawater, atmosphere andground habitats. They dwell in rotting vegetables and fruit, inmoulds, exudates of trees and their barks, in xylophage insects,pig\u2019s intestine, milk of cows suffering from mastitis, in forest,garden and swampy soils, especially drenched with sewagewaters, in sea weed and so on . These environmental preferencesare most likely due to discharge of methoxyl groups duringdegradation of lignin and pectin . Inaddition to fruit juices and soil samples, methylotrophic yeastsare also found in food .Many types of yeast are wide-spread while some are limitedonly to a certain narrow habitat. They rarely occur in naturein absence of micellar fungi and bacteria. Therefore, to obtainthem one must use selective methods allowing yeasts to haveadvantages in growth speed. When media for selective isolationof yeasts are developed, low \u0440\u041d is usually used as in themajority of cases yeasts prevail over bacteria in such conditions.Media could also include antibiotics for suppressionof bacteria and fungistatic agents for suppression of moulds.When yeasts are present in great amounts, they can beisolated by direct application of the material or its suspensionon sour agarized medium that can also be enriched withantibiotics or have other selecting properties. Agar hydrolyzesin low-\u0440\u041d medium during autoclaving. Therefore agar andmedium are sterilized separately, cooled to around 45 \u00b0\u0421,mixed and distributed among Petrie dishes. The majority ofyeast species can be isolated at 3.7 \u0440\u041d, but some species suchas Schizosaccharomyces species require higher \u0440\u041d rangingfrom 4.5 to 5.0. If yeasts are present in the sample in lowquantities, their population could be increased by preliminaryincubation of the sample in liquid medium at \u0440\u041d up to 3.8.To isolate specific physiological groups of yeasts, it\u2019s necessaryto find additional selecting parameters. Methylotrophicyeasts can be selected with use of methanol as the sole sourceof carbon and energy in the medium. Thus, when methylotrophicyeasts were isolated from grape leaves in Thailand,YNB medium with extra 0.5 % of methanol was used to getthe enrichment culture. Cultivation continued for 4\u20135 daysat 27 \u00b0\u0421, following which enrichment cultures were spreadon 0.5 % v/v methanol-YNB agar. As a result, 2 new specieswere isolated that classified as Ogataea .Methylotrophic yeasts are wide-spread as a platform forproduction of recombinant protein. Initially, they became ofinterest to biotech companies as single-cell protein producers.However, due to the 1973 oil crisis, methanol grew in priceand isolation of feed protein from it became irrelevant. At the same time, due to discovery of proteins key to molecularbiology such as thermotolerant polymerases, lygases andrestrictases, various microorganisms modification methodsstarted being developed, including those for production ofrecombinant proteins.Production of proteins with use of microorganisms for variouspurposes, in the first place, for food and animal feed aswell as technological purposes, has been actively developingsince 1940s. In the first place, this was connected with the useof natural producers, upgraded in many cases with the helpof undirected mutagenesis methods. As molecular biologymethods developed, it became possible to develop proteinproducers untypical for a specific organism (heterologous orrecombinant proteins), including with use of yeasts.Following this trend, Phillips Petroleum developed theirown P. pastoris-based expression system for productionof recombinant proteins (later renamed into Komagataellaphaffii). Thanks to its outstanding properties as well as PhillipsPetroleum\u2019s decision to allow its wide-spread utilization forscientific purposes around the world, it got widely popular asa recombinant protein production platform.Understanding of key properties that made P. pastorisbasedexpression systems popular is important for furtherdevelopment of protein-expressing platforms. Number one ishigh protein production level. It\u2019s lower than that of bacteriaand micellar fungi but higher than that of other systems, i. e.cells of mammals, plants and insects. Number two: yeasts areeukaryotes, and they have all cell compartments necessaryfor synthesis and assembly of eukaryotic proteins, which allowsthem to synthesize proteins that cannot be synthesizedwith use of bacterial expression systems. Number three isextracellular protein\u2019s ability to synthesize, which brings thecosts of the production process down. Number four is thelow level of glycosylation of proteins in comparison to manyother types of yeast.Other methylotrophic yeasts, except K. phaffii, have alsobeen tried out as a platform for expression of recombinantprotein. In the first place, it should be noted that P. pastorisstrain CBS7435 initial for the Invitrogen\u2019s system was suggestedto be used as a patent-independent platform. In Russia,Komagataella kurtzmanii strain of American origin waspatented. Alternative Ogataea-based expression platformswere developed in the USA: Hansenula (Ogataea) polymorphaand Pichia (Ogataea) methanolica, the latter belongs toInvitrogen. In Japan, there was developed an alternative platformon the basis of Candida boidinii. This system was beingdeveloped until 2009, but since then this organism has not beenmentioned as a platform used for production of recombinantprotein. In Malaysia, strain P. guilliermondii (Meyerozymaguilliermondii) was suggested for production of protein.One can notice that all yeast strains used for productionof heterologous proteins up to 2009 have American origin.This sets a question, whether or not American isolates haveunique properties allowing for production of protein in yeasts.More recent works witness that it\u2019s not accurate. First strainswere developed by American researchers working in onestate. Actually, rapid development of bioscience, includingdiscovery of new methods of molecular biology, took placein the US Southwest. It seems that this fact was the key reasonfor using strains of this region specifically. The Russian patent is actually the copy of known systems, which requiresutilization of the closest species that in the majority of caseshave geographically similar habitats.Overall, alternative methylotrophic-yeasts-based systemshaven\u2019t become popular. Reasons are multiple. Lack of intereston part of recombinant proteins market players and disabilityof new players to enter this market with a new system alongwith lack of acute need for it is the main reason. For example,Chinese manufacturers actively use strains obtained on thebasis of Invitrogen\u2019s strains. It shall also be noted that modernstrains may be significantly genetically modified to ensurehigher yields of recombinant proteins.The authors declare no conflict of interest.Abu M.L., Nooh H.M., Oslan S.N., Salleh A.B. Optimization of physicalconditions for the production of thermostable T1 lipase in Pichiaguilliermondii strain SO using response surface methodology. BMCBiotechnol. 2017;17:78. 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Ideally one should model all covariates in unison, but most existing analysis methods for genome-wide association studies (GWAS) perform only univariate regression.We extend and efficiently implement iterative hard thresholding (IHT) for multiple regression, treating all SNPs simultaneously. Our extensions accommodate generalized linear models, prior information on genetic variants, and grouping of variants. In our simulations, IHT recovers up to 30% more true predictors than SNP-by-SNP association testing and exhibits a 2\u20133 orders of magnitude decrease in false-positive rates compared with lasso regression. We also test IHT on the UK Biobank hypertension phenotypes and the Northern Finland Birth Cohort of 1966 cardiovascular phenotypes. We find that IHT scales to the large datasets of contemporary human genetics and recovers the plausible genetic variants identified by previous studies.Our real data analysis and simulation studies suggest that IHT can (i) recover highly correlated predictors, (ii) avoid over-fitting, (iii) deliver better true-positive and false-positive rates than either marginal testing or lasso regression, (iv) recover unbiased regression coefficients, (v) exploit prior information and group-sparsity, and (vi) be used with biobank-sized datasets. Although these advances are studied for genome-wide association studies inference, our extensions are pertinent to other regression problems with large numbers of predictors. This tactic allows one to fit biobank-scale data in less than one day, assuming enough storage space and computers are available. The latter tactic requires cycling through the training sets sequentially. Because intermediate data can be deleted, this tactic only requires enough disk space and RAM to store one copy of the training set. MendelIHT.jl uses one of Julia\u2019s [Distributed.jl, to achieve the aforementioned parallel strategies. Julia\u2019s standardMendelIHT.jl clamps values of In Poisson and negative binomial regressions, the inverse link argument For each proposed IHT step we check whether the objective Project name: MendelIHThttps://github.com/OpenMendel/MendelIHT.jlProject home page: Operating systems: Mac OS, Linux, WindowsProgramming language: Julia 1.0, 1.2License: MITRRID:SCR_018292bio.tools/mendeliht.jlbio.tools ID: MendelIHT.jl interfaces with the OpenMendel [SnpArrays.jl [Distribution.jl [GLM.jl [The code to generate simulated data, as well as their subsequent analysis, is available in our GitHub repository under the \"figures\" folder. Project.toml and Manifest.toml files can be used together to instantiate the same computing environment in our article. Notably, enMendel package rrays.jl and Juliution.jl and GLM. [GLM.jl .GigaScience Database, GigaDB [The Northern Finland Birth Cohort 1966 (NFBC1966) was down, GigaDB .Supplementary information: Supplementary data are available in GigaDB.giaa044_GIGA-D-19-00398_Original_SubmissionClick here for additional data file.giaa044_GIGA-D-19-00398_Revision_1Click here for additional data file.giaa044_GIGA-D-19-00398_Revision_2Click here for additional data file.giaa044_Response_to_Reviewer_Comments_Original_SubmissionClick here for additional data file.giaa044_Response_to_Reviewer_Comments_Revision_1Click here for additional data file.giaa044_Reviewer_1_Report_Original_SubmissionJian Zeng -- 12/15/2019 ReviewedClick here for additional data file.giaa044_Reviewer_1_Report_Revision_1Jian Zeng -- 3/4/2020 ReviewedClick here for additional data file.BLAS: Basic Linear Algebra Subprograms; BMI: body mass index; bp: base pairs; CPU: central processing unit; DBP: diastolic blood pressure; GLM: generalized linear models; GWAS: genome-wide association studies; HDL: high-density lipoprotein; HTP: hard thresholding pursuit; IHT: iterative hard threhsolding; LD: linkage disequilibrium; LDL: low-density lipoprotein; MAF: minor-allele frequency; MCP: minimax concave penalty; Neg Bin: negative binomial; NFBC: Northern Finland Birth Cohort; NHLBI: National Heart, Lung, and Blood Institute; NIH: National Institutes of Health; NIHT: normalized iterative hard threshold algorithm; RAM: random access memory; S2 Hyp: Stage 2 hypertension; SBP: systolic blood pressure; SNP: single-nucleotide polymorphism.The authors declare that they have no competing interests.As described in , informeB.B.C. was supported by NIH T32-HG002536 training grant and the 2018 Google Summer of Code. K.L.K. was supported by a diversity supplement to NHLBI grant R01HL135156, the UCSF Bakar Computational Health Sciences Institute, the Gordon and Betty Moore Foundation grant GBMF3834, and the Alfred P. Sloan Foundation grant 2013-10-27 to UC Berkeley through the Moore-Sloan Data Sciences Environment initiative at the Berkeley Institute for Data Science (BIDS). E.M.S, K.L., and H.Z. were supported by grants from the National Human Genome Research Institute (HG006139) and the National Institute of General Medical Sciences (GM053275). J.S.S. was supported by grants from the National Institute of General Medical Sciences (GM053275), the National Human Genome Research Institute (HG009120), and the National Science Foundation (DMS-1264153). C.A.G. was supported by the Burroughs Wellcome Fund Inter-school Training Program in Chronic Diseases (BWF-CHIP).B.B.C., K.L.K., E.M.S., J.S.S., and K.L. contributed to the design of the study, interpretation of results, and writing of the original draft manuscript. B.B.C. designed and implemented the simulations and conducted the data analyses. C.A.G., H.Z., and J.J.Z. contributed to the analysis of UK Biobank results. B.B.C. and K.L.K. developed the software. B.B.C. and K.L. developed the algorithms. E.M.S. assisted in the comparisons to marginal GWAS. All authors have read, made suggestions, and ultimately approved the final manuscript."} +{"text": "Bryumperspinidens, has been discovered in Guyana with erect capsules and a short inner peristome. The Guyana material is recognized as a new species, and both species are placed in the genus Brachymenium. The characteristics that distinquish the genus are discussed with reference to the Guyana specimens of Brachymeniumspeciosum.A relative of the African species described by Brotherus as Brachymenium Schwaegr., Spec. Musc. Suppl. 2(1): 131. 1824, with a leaf that superficially matches the illustration of Bryumperspinidens Broth. in the Brotherus treatments in the two editions (1904 and 1925) of Engler and Prantl. The only problems were that the Brotherus illustration was of an African species named as a Bryum. The spiniform teeth of the leaf margins were nevertheless similar, and a relationship seemed to be involved. As for the generic placement, the Bryum Hedw. lacked any real evidence. The relationship of Guyana Highland species to African species fits a pattern noted by Brachymenium, B.speciosum that is newly discussed and illustrated.Study of bryophyte collections obtained during the Smithsonian Biological Diversity of the Guianas project, has revealed a number of interesting species. Among these are two two collections of a bryaceous moss with capsules identifiable as a Specimens in this study were obtained during the Smithsonian Biological Diversity of the Guianas Program conducted over a period of years from 1985 to 2014 . The parA note with the specimens indicates that when they arrived in the US they were irradiated during the Anthrax scare of 2001.The South American material includes one species that seems to be distinct from others from the Western Hemisphere .Guyana. Region: Potaro\u2013Siparuni. Mt. Ayanganna, east face, plateau above second of four escarpments. 1380 m, Stems up to 3 cm tall, leaves not closely spaced, rather firm in structure but contorted when dry and resistant to wetting. Costa percurrent into a long slender acumination, median cells narrowly oval, with firm walls showing slight porosity, mostly 80\u2013100 \u03bcm long and ca. 30 \u03bcm wide, without shorter quadrate cells at base, margin with numerous rows of linear pale cells forming a strong border, border with numerous cells projecting as spiniform teeth, such spiniform teeth extending onto apical acumination. Synoicous? Seta pale yellowish-red, ca. 17 mm long, smooth. Capsules erect, ca. 2 mm long, with short hypophysis, operculum short-rostrate, higher than wide. Outer peristome teeth reddish, rudimentary, ca. 80 \u03bcm long, inner peristome a low pale membrane ca. 70 \u03bcm without projecting segments or cilia. Calyptra not seen. Spores ca. 10 \u03bcm in size.05\u00b023.083'N, 059\u00b058.550'W. Dense forest on sandstone and peat, with Euterpe, Clusia, and Brocchinia. Sporophytes green. On tree limb. H.D. Clarke 9551 with R. Williams, C. Perry, E. Tripp & J. Kelly (US).Guyana. Region: Potaro\u2013Siparuni. Mt. Ayanganna, east face, area near camp at base of fourth of four escarpments. Elev. 1545 m, The peristome teeth of the new species have proven extremely fragile, possibly because of the radiation treatment.The spiniform teeth of the leaf margin are distinctive, but the manner in which they occur on the acuminate apical extension is reminiscent of the illustration by Ochi (1972)Bryum only because there was no sporophyte to indicate otherwise. A important point derived from the Ochi study is that none of the species in typical Bryum have spinose marginal teeth, all with such teeth are in what is now in the Brachymenium, Rhodobryum relationship. On the basis of the evident relationship between the African and Guyana species, the following transfer of the African species is provided.The African species is well illustrated by Taxon classificationPlantaeBryalesBryaceae(Broth.) H.Rob. & G.K.Golinskicomb. nov.673E4191-B2F7-52F6-B9C3-CE439A8FCF10BryumperspinidensScott Elliot 266, Sterile. Rhodobryumperspinidens (Broth.) P\u00f3cs, in Bizot & P\u00f3cs, Acta Bot. Acad. Sci. Hungaricae 25: 257. 1979 [1980]. With record of species from Tanzania, also sterile. BryumHedw.subgenusRhodobryum Schimp. in which he placed it. Broth., Bot. Jahrb. Syst. 24: 246. 1897. Britische Ostafrika, Seengebiet: Ru\u2013 Nss\u00f3ro, 3300\u20133600 m , Brachymenium is based on the capsules being erect with an inner peristome being a low membrane lacking segments or cilia, the traditional distinctions of the genus. Recent DNA studies Hampe, Linnaea 38: 663. 1874, a later established genus and Osculatia De Not., Mem. Reale Accad. Sci. Torino, ser 2, 18: 445. 1859 Steere.17399882-F918-5D65-968F-86F1F8CCAEAAThe latter species has been collected on a mountain near Ayanganna as indicated below.5\u00b05'8\"N, 59\u00b050'32\"W. elev. 1525 m. Tepui scrub forest on sandstone and peat, with Schefflera, Clusia and Guadua. 5 July 2003, H.D. Clarke 10550, with R. Williams, C. Perry, J. Kelly, D. Gittens, S. Stern; Guiana. Mt. Wokomung, Little Ayanganna, upper slopes of highest point of Mount Wokomung massif. 5\u00b05'8\"N, 59\u00b050'32\"W. elev. 1525 m. Tepui scrub forest on sandstone and peat, with Schefflera, Clusia and Guadua, elev. 1525 m. 5 July 2003, H.D. Clarke 10575, with R. Williams, C. Perry, J. Kelly, D. Gittens, S. Stern. Guiana. Mt. Wokomung, Little Ayanganna, upper slopes of highest point of Mount Wokomung massif. 5\u00b04'53.1\"N, 59\u00b050'26.1\"W. elev. 1525 m. Tepui bog on sandstone and peat, with Brocchinia, Bonnetia and Rapatea, elev. 1660 m. 6 July 2003, H.D. Clarke 10576, with R. Williams, C. Perry, J. Kelly, D. Gittens, S. Stern. Mt. Wokomung, area above third of four escarpments, 1 km NE of Mt. Wokomung, 5\u00b04'30\"N, 59\u00b051'15\"W. elev. 1490 m. dense forest on laterite, with Clusia, Euterpe and Licania, elev. 1490 m. 8 July 2003, H.D. Clarke 10802, with R. Williams, C. Perry, J. Kelly, D. Gittens, S. Stern. The material shows the additional feature of the species, the multistratose leaf margin with teeth on the margin and upper and lower surfaces. The species is otherwise reported from Suriname, Ecuador, and supposedly described from Jamaica ."} +{"text": "Licania salicifolia (L.S) Cuatrec., Persea ferruginea (P.F) Kunth, Oreopanaxfloribundus (O.F), and Psychotria buchtienii (P.B) belong to the families Chrysobalanaceae, Lauraceae, Araliaceae, and Rubiaceae, respectively, which have been used as medicines by communities in the Andes. This study evaluated the leishmanicidal and cytotoxic activities of alcohol and non-alcohol extracts from four Andean plant extracts .in vitro to determine the leishmanicidal activity against amastigotes of Leishmania panamensis and cytotoxicity against U937 cells.Extracts were obtained by percolation with solvents of different polarities \u2014 hexane, dichloromethane, ethyl acetate, and ethanol. Phytochemical screening was conducted based on reported methods. All products were evaluated 50 <30 \u03bcg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 \u03bcg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extracts from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 \u03bcg/mL, respectively. Hexane and ethanol extracts from O.F, ethyl acetate, and ethanol extracts from L.S, and all extracts from P.F were not toxic. Alternatively, hexane and dichloromethane extracts from L.S and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high toxicity.Flavonoids, triterpenes, and tannins were the main secondary metabolites found. From the results, dichloromethane extracts from O.F and P.B, ethanol extract from P.B, and ethyl acetate extracts of all plants were active, with ECBased on the activity we observed, ethyl acetate extract can continue in its usage in the search for new antileishmanial drugs, mainly ethyl acetate extract from L.S showed activity comparable to meglumine antimoniate and was not cytotoxic. Leishmania, which infect and replicate inside macrophages of the vertebrate host. These diseases are considered a major health problem because of its presence in 98 countries, affecting mostly low-income people in rural areas of tropical and subtropical countries (1)50) determined by the probit method [The antileishmanial activity was determined according to the percentage of infected cells and parasite load obtained for each experimental condition using flow cytometry. The results of antileishmanial activity were expressed as the median effective concentration (ECt method using th% Parasitemia = 1 \u2013 [(MFI Exposed parasites) /(MFI Control parasites) \u00d7 100] (2)50 value . In turn, leishmanicidal activity was graded according to the EC50 or IC50 value .The cytotoxicity was graded according to the LCThe selectivity index (SI) was calculated by dividing the cytotoxic activity and the leishmanicidal activity using the following formula:50/EC50SI = LCExperiments were repeated at least 3 times for each concentration. Statgraphics Plus program version 5.0 was used for all regression calculations with a significance level of p<0.05., P.F, O.F, and P.B are reported in Extraction yield and phytochemical results for hexane, dichloromethane, ethyl acetate, and ethanol extracts for L.SL. (V) panamensis parasites. Alternatively, the antiparasitic activity of these extracts was tested on intracellular amastigotes of L. (V) panamensis according to their ability to reduce the number of parasites after exposure. The results are summarized in The effects of extracts on cell growth (viability) were assessed in human macrophages (U937 cells), which are the host cells for , P.F, and O.F with a percentage yield of 17.0, 6.2, and 8.5%, respectively, and hexane extract from P.B with a percentage yield of 15.1%. The preliminary phytochemical analysis of the extracts revealed triterpenes in hexane, dichloromethane, and ethyl acetate extracts, while, tannins, leucoanthocyanidins, and saponins were only present in ethanol extracts of all plants. Alkaloids were found only in the ethanol extract from P.F. The presence of coumarins was found in the ethanol extract from L.S, as well as in ethyl acetate and ethanol extracts from P.F and P.B.50 <30 \u03bcg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 \u03bcg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extract from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 \u03bcg/mL, respectively. The activity of these extracts was probably due to the presence of compounds such as terpenoids, flavonoids, and coumarins .Unfortunately, hexane extracts from L.S and P.F, dichloromethane extract from L.S, and ethanol extract from L.S, P.F, and O.F displayed leishmanicidal activity but at concentrations toxic to U937 cells, which serve as host cells of L. salicifolia and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high cytotoxicity in a manner similar to Amphotericin B.Hexane and ethanol extracts from O.F, ethyl acetate and ethanol extracts from L.S, ethanol extract from P.B, all extracts from P.F, and pentavalent antimonial (meglumine antimoniate) were not toxic. Alternatively, hexane, and dichloromethane extracts from L. (V) panamensis than U937 cells. Leishmanicidal activity displayed by these extracts against intracellular amastigotes of L. (V) panamensis suggests that they are promising candidates in the search for new antileishmanial compounds, mainly ethyl acetate extract from L.S, exhibited high SI and activity comparable to the conventional drug - meglumine antimoniate.Except for the hexane extract from P.B, all SIs suggest that these extracts are selective since they were more active against The antileishmanial and cytotoxic screening of 16 extracts from four species of Colombian plants were reported. Based on activities observed, ethyl acetate extracts from all plants can continue in its usage in the search for new antileishmanial drugs, although further studies are required.Different lineages of angiosperms produce useful metabolites for treating tropical diseases. In this study, it was shown that different species belonging to the Magnoliids \u2014 a basal group within the flowering plants \u2014 and the rest, which belongs to much more recent lineages, are endowed with molecules that can control tropical parasites. This is evident that the molecules of interest for controlling these diseases are widely distributed in the lineages of flowering plants.WC, FA, and SR conceived the study designed. FA collected plant material. CH, JC, and IDV performed the experiment. AY and IVT analyzed the data. WC and SR drafted and revised the manuscript. All authors read and approved the final manuscript."} +{"text": "Methanobacterium ruminantium in a pressureized atmosphere. Appl. Environ. Microbiol. 32, 781\u2013791. It should be Balch, W. E., Fox, G. E., Magrum, L. J., Woese, C. R., and Wolfe, R. S. (1979). Methanogens: reevaluation of a unique biological group. Microbiol. Rev. 43, 260\u2013296.In the original article, the reference for Balch et al. was incoThe 2 L steel anaerobic canister used in our study was a modified version of a pressure cylinder described in Figure 5 of the above-mentioned publication (Balch et al., The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports10.1038/s41598-020-57945-4, published online 22 January 2020Correction to: Xiuqian Mu was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:M.T., A.H., E.K., J.-L.B., J.C.G., N.D., F.T. and F.C. designed the experiments. M.H.-F., X.M. and A.G. provided mice and contributed to initial discussions. M.T., A.H., O.S., E.K., J.-L.B., N.D., S.D. and C.B. performed the experiments, M.T., A.H., O.S., E.K., and J.-L.B. contributed to data analyses and all the authors discussed the data for interpretation. M.T. and F.C. wrote the initial draft of the manuscript, and revisions were made by J.C.G., J.-L.B., E.K., A.G., M.T. and F.C.In addition, the Acknowledgements section now reads:We thank members of the NEDI lab for material, technical support and discussions. This work was supported by grants from the \"Fonds sp\u00e9ciaux de recherche\" (FSR) of the Universit\u00e9 catholique de Louvain, by the \"Actions de Recherche Concert\u00e9es (ARC)\" #17/22-079 of the \"Direction g\u00e9n\u00e9rale de l\u2019Enseignement non obligatoire et de la Recherche scientifique \u2013 Direction de la Recherche scientifique \u2013 Communaut\u00e9 fran\u00e7aise de Belgique\" and granted by the \"Acad\u00e9mie universitaire \u2018Louvain\u2019\", by a \"Projet de recherche (PDR)\" #T.0117.13 and an \"Equipement (EQP)\" funding #U.N027.14 of the Fonds de la Recherche Scientifique (F.R.S.-FNRS) and by the Association Belge contre les Maladies neuro-Musculaires to F.C., by South-East Norway Health Authority grant no. 2014119 to J.-L.B., by Norwegian Research Council grant no. 230000/F20 and EU-funded ERA-NET Neuron grant (CERMOD) to J.C.G., by a grant (R01EY029705) from the National Institutes of Health/National Eye Institute to X.M. and by NINDS in the National Institutes of Health, grant no. NS102678 to A.G. A.H., S.D. and C.B. held FRIA grants and M.H.-F. held a Research Associate grant from the F.R.S.-FNRS. F.C. and F.T. are Senior Research Associate and Research Director of the F.R.S.-FNRS, respectively."} +{"text": "Diaphorina citri (Hemiptera: Liviidae) on Valencia Orange Influenced by Sex, Color, and Size. J. Insect. Sci.\u201dCorrection of \u201cEbert T. A. and M. E. Rogers. 2020. Probing Behavior of 10.1093/jisesa/ieaa016DOI: In the original version of this article, the supplementary material was not available. This material now appears online. The journal regrets this error."} +{"text": "Scientific Reports 10.1038/s41598-020-71118-3, published online 25 August 2020Correction to: This Article contains errors.Mate Hidvegi was omitted from the author list in the original version of this Article.As a result, the Acknowledgements section,\u201cWe are grateful to Mate Hidvegi for the generous gift of the freeze-dried fermented wheat germ extract used as the control in the in vivo study and as starting material in the isolation process. We are also thankful to Geoffrey Girnun and Emily Montal for their expertise in metabolomics and Seahorse analysis and for the helpful discussions.\u201dnow reads:\u201cWe are thankful to Geoffrey Girnun and Emily Montal for their expertise in metabolomics and Seahorse analysis and for the helpful discussions.\u201dThe Author Contributions section now reads:G.B., S.B. and K.R. carried out the experiment. G.B. wrote the manuscript with support from S.B., J.D.W, L.O., N.K.T and D.P. K.R. fabricated the proteomics sample. J.D.W and N.K.T. helped supervise the project. H.M. is the originator of the research and provided the freeze-dried form of fermented wheat germ extract. G.B. and D.P. conceived the original idea. D.P. supervised the project.In addition, the authors neglected to include some potential conflicts of interest. The Competing Interests section now reads:G.B. is an employee of American Biosciences Inc., and co-founder of Mitomarin Inc. G.B performed this research while he was a Visiting Scientist at Cold Spring Harbor Laboratory with financial support from American Biosciences Inc. G.B., L.O., D.P., H.M., N.K.T., and J.W. are inventors of patent applications covering A250 H.M. has received travel compensation funds from American Biosciences, Inc. between 2009-2012. The rest of the authors declare no competing interests.Lastly, an affiliation for author Gyula Bencze was omitted. The correct affiliations for Gyula Bencze are listed below:Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USAAmerican Biosciences, Inc, Blauvelt, NY 10913, USAThese errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Front Neurosci. (2017) 11:353. doi: 10.3389/fnins.2017.00353 It should be Haghshomar M, Rahmani F, Hadi Aarabi M, Shahjouei S, Sobhani S, Rahmani M. White matter changes correlates of peripheral neuroinflammation in patients with Parkinson's disease. Neuroscience. (2019) 403:70\u20138. doi: 10.1016/j.neuroscience.2017.10.050.In the original article, reference 31 was incorrectly written as Haghshomar M, Rahmani F. Cognitive challenge to choose healthier food is reflected in heart rate variability. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "The color of the grain shell of cereals is an important feature that characterizes the pigments andmetabolites contained in it. The grain shell is the main barrier between the grain and the environment, so itscharacteristics are associated with a number of important biological functions: moisture absorption, grain viability, resistance to pre-harvest germination. The presence of pigments in the shell affects various technological properties of the grain. Color characteristics, as well as the appearance of the grain shell are an importantindicator of plant diseases. In addition, the color of the grains serves as a classifying feature of plants. Geneticcontrol of the color formation of both grains and other plant organs is exerted by genes encoding enzymesinvolved in the biosynthesis of pigments, as well as regulatory genes. For a number of pigments, these genesare well understood, but for some pigments, such as melanin, which causes the black color of grains in barley, the molecular mechanisms of biosynthesis are still poorly understood. When studying the mechanisms ofgenetic control of grain color, breeders and geneticists are constantly faced with the need to assess the colorcharacteristics of their shell. The technical means of addressing this problem include spectrophotometers,spectrometers, hyperspectral cameras. However, these cameras are expensive, especially with high resolution,both spatial and spectral. An alternative is to use digital cameras that allow you to get high-quality imageswith high spatial and color resolution. In this regard, recently, in the field of plant phenotyping, methods forevaluating the color and texture characteristics of cereals based on the analysis of two-dimensional imagesobtained by digital cameras have been intensively developed. This mini-review is devoted to the main tasksrelated to the analysis of color and texture characteristics of cereals, and to methods of their description basedon digital images. The coloration of cereal grain shell is an important traitthat characterizes the pigments and metabolites containedthere. Violet and blue grain color is determined by anthocyans; yellow color, by carotenoids; and red brownor dark brown, by flavonoids, such as proanthocyanidinsand phlobaphenes . The correlation between the shell color andcontent of the corresponding substances is experimentally demonstrated. Significant correlations of the kernelshell color and the content of phenols, flavonoids, andantioxidant capacity have been observed . The contents of phenols, flavonoids, anthocyans,\u03b2-carotenoids, and luteins significantly differ betweenthe maize grains with different colors .Flavonoids, anthocyans, and carotenoids possess severalvaluable properties. They are antioxidants, and influencethe nutritional value. For example, addition of the wheatseed coats with a purple pericarp or blue aleurone layerto flour improves the quality of bakery products owing toflavor, texture, and color characteristics . Correspondingly, the varieties and lines withdifferent grain coloration recently cause a strong interestof the food industry .The kernel shell is the main barrier between the grainand environment; correspondingly, a set of important biological functions are associated with the shell properties,including, water absorption, grain viability, and resistanceto pre-harvest sprouting .The pigments in the grain shell influence manifold graintechnological properties. In particular, phlobaphenes(condensed tannins), coloring the pericarp red, have apositive effect on the duration of grain dormancy, therebypreventing its pre-harvest sprouting . That is why the wheat genotypes with red-coloredkernels are used in breeding as a donor of the genes controlling the resistance to pre-harvest grain germination. Theshell color of rice kernels correlates with the grain quality characteristics, such as kernel transparency andthe share of broken kernels, in a statistically significantmanner .The color characteristics and the external appearance ofthe kernel shell are important indicators of plant diseases.For example, fusariosis manifests as a pinky or bluishcoloration on the wheat and barley kernel shell . Characteristic of another disease, kernelblack-point, is dark discoloration of the embryo side ofgrains .Grain coloration may also serve as a trait in plantclassification. As early as the late 19th century, F. K\u00f6rnicke suggested using the grain color for descriptionof wheat botanical varieties .The N.I. Vavilov All-Russian Institute of Plant GeneticResources classifies the wheat botanical varieties usingthe system in which the grain color is one of the majortraits .The coloration of both the kernels and other plantorgans is controlled by the genes coding for the enzymes involved in biosynthesis of pigments, as well asby regulatory genes . The corresponding genesare well studied for several pigments, including eventheir complete nucleotide sequences and their positionsin the genome. However, the molecular mechanisms ofbiosynthesis are still rather vague for some pigments,in particular, melanin, which determines black color ofbarley kernels . When studying the mechanisms underlying geneticcontrol of grain color, breeders and geneticists constantlyface the necessity of estimating the color characteristicsof their shells. Several technical tools allow this problemto be solved, first and foremost, spectrophotometers, ableto characterize both the chromatic and textural characteristics of kernels with a high accuracy. Spectrophotometers have been long and successfully used and serve asa standard for estimating the color of biological objects. Another approach is provided by spectrometerswith the wavelength range covering both visible and nearinfrared regions . However, these cameras are very expensive,especially, with a high spatial and spectral resolution.An alternative is digital cameras capturing high-qualityimages with a high spatial and color resolution. Theprice of digital cameras are constantly decreasing andthey are now widely available, while even an amateurcamera allows for capturing high-resolution and highquality images. In this regard, the methods for evaluating the color and texture characteristics of cereal grainsbased on analysis of two-dimensional digital images havebeen intensively developed recently in the field of plantphenotyping.This brief review focuses on the main problems relatedto the analysis of color and texture characteristics ofcereals and methods of their description utilizing digitalimages.One of the relevant problems in the analysis of digitalimages of grains is related to classification. The particulartasks of classification may be different. For example, it isnecessary to classify grains according to their color andsurface texture into several different genotypes . Frequently, the characteristics of size and shape are added to the color andtexture parameters .Another tightly associated problem is to assort thekernels according to color and surface texture ; in particular, sorters are designed for mass screening of a large number of grains to separate the soundgrains from waste and damaged grains. M. Huang et al.(2015) reviewed the current developments on the seedquality and safety tests based on image analysis, including hyperspectral ones, and Z. Gong et al. (2015) brieflydescribe the approaches, engineering included, to the seedquality inspection.Sometimes the grains are classified only by their color(red or white). In particular, M.S. Ram et al. (2002) usedspectrophotometer and spectrometer to design a procedure for determining the color of kernel shell in red andwhite wheats. T.N. McCaig et al. (1993) classified thewheat into red-grained and white-grained cultivars usingthe spectrophotometry data for 262 genotypes of bothsoft and hard wheats. Analysis of the color characteristicsalso makes it possible to identify the kernels affected bypathogens ormechanically damaged . Note thatmachine learning and artificial intelligence techniquesare also frequently used along with the image analysisin solving the relevant problems ; however, the description of these methods is beyond thearea of our review.The color of the surface is a characteristic of its spectralreflectivity, which is determined by many factors, suchas absorption of radiation of a light source at differentwavelengths, its reflection, and scattering . Spectrometers give the fullest estimate of the reflection and absorption characteristics in different rangesof wavelengths. As for the most of the digital cameras,their sensors respond to reflected radiation in the visiblewavelength range (400\u2013780 nm). Note that the colorperception by the human eye has its specific featuresassociated with its structure: there is no one-to-one correspondence between the surface color perception by theeye and the spectral characteristics of this surface; forexample, the same shade of gray can be reproduced bythe reflected radiation with completely different intensities for different wavelengths.When studying the human perception, it was found outthat three main colors \u2013 red, green, and blue \u2013 are sufficient to get the overall set of colors perceived by humansby mixing them in different proportions . This inference is confirmed by the structure ofthe human eye itself since the eye retina comprises threetypes of receptors responsible for colorvision.Different models (color spaces) have been elaboratedto digitally represent colors. Color model specifies thesystem of coordinates that unambiguously determinescolors. Several different color models have been developed to provide the best method of color descriptionfor TV, photo, video, and color printing. The followingsystems are most frequently used when analyzing digitalimages of plants.The RGB color model is the most well known colorspace, encoding a broad array of colors by relative intensities of its three components: red (R), green (G), andblue (B). These components are described by integers,most frequently from 0 to 256. The higher the values,the higher is the intensity of color (luminance). The colors with equal values of the components are the shadesof gray. This representation is used mainly in computerscreens and digital cameras.The HSV (HSB) model is a color space also using threecolor components, proposed in the mid-1970s. The huecomponent (H) varies from 0 to 360; the values close to 0and 360 correspond to red; close to 60, to yellow; 120, togreen; 180, to cyan; 240, to blue; and 300, to magenta.Saturation (S) is the larger, the more saturated is the colortone, while small values of this parameter correspond tothe shades of gray. Brightness takes on thesmaller values for the dark colors and larger, for bright ones. One of the shortcomings of the HSV and RGBconsists in that the number of saturation and color tintlevels perceptible to eye in these spaces decreases whenbrightness approaches zeroThe CIE L*a*b* space, proposed in 1976 by theInternational Commission on Illumination (CIE), wasdesigned to approximate the human vision and to provideperceptual uniformity. Similar to HSV, the brightnesscomponent in CIE L*a*b* (L* component) is separatedfrom the chromatic component of color and is an approximate estimate of brightness. Thea* parameter takes on the positive values for reddish tintsand negative values for greenish ones; the b* parameteris positive for the yellowish tints and negative for thebluish ones. This color model is widely used in softwaresolutions for image processing and color correction. TheCIE L*a*b* space is used for assessing the color characteristics in spectrophotometers.The characteristics of other color spaces with their description are available in specialized literature on imageanalysis . The components of the same color indifferent systems are linked by transformation rules, sothat knowing the values of the chromatic componentsfor a color tint in one space, the corresponding valuesfor another space are obtainable. For example, the valuesfor the RGB components make it possible to computethe values for the HSV components and vice versa. Thisallows the color representation for a particular image tobe selected depending on the particular taskWhen solving a problem of machine vision and analysisof chromatic characteristics, the HSV and L*a*b* colormodels are of the principal interest since these systemsrepresent colors in the same terms as a human does whendescribing a color, namely, hue, saturation, and brightness (lightness).The images used for analyzing kernels are as a rule captured by digital cameras in the RGB space shot underlaboratory conditions using a controlled illumination.The kernels in images are typically placed onto a contrastbackground at a distance from one another . This protocol makes itpossible to analyze not only the color and surface texturecharacteristics, but also the kernel shape and size. Moreover, bulk specimens are used in some studies in which the kernels lie ina dense grain touching one another. As a rule, the texturaland chromatic characteristics of the bulk specimen areassessed in this approach rather than individual kernels.In the case the individual kernels are analyzed, first,their local images are isolated in the integral image.For this purpose, the images are preprocessed andsegmented to identify the regions of the image that correspond to individual kernels. Then, the quantitative traitsavailable from images are extracted from these regions.Note that it is rather difficult to control the illuminationconditions, especially when the images are capturedoutside laboratory . Correspondingly,color correction procedure using color patterns (a set ofcards with cells of specified standard colors) is helpful.In an image, the regions corresponding to individualkernels comprise hundred of pixels, each displaying itsown color characteristics in a selected color space .That is why statistical characteristics of color componentsare most frequently used for description of the color ofthese objects. First and foremost, the histograms of pixeldistribution according to the intensity of each color component independently of the other components and thelocation of pixels in the image are computed. The histograms are used to calculate the other parameters, such asthe mean value, variance, asymmetry, and the kurtosis ofpixel intensities for each color component . These values are furtherutilized to describe the color properties of kernels.In particular, T. Pearson and D. Brabec (2008) developed a system of machine vision for an automatedestimation and sorting of the kernels of wheat and othercereals in a real-time mode. The images with a resolutionof 640\u00d7480 pixels were captured with a digital cameraand transferred to a PC, which, after classification, outputa signal to an air valve to correspondingly sort the kernels.The intensity histograms as well as the mean and standard deviations of the RGB channel intensities were used for classification by linear discriminant analysis. The accuracyof the system when classifying red and white kernels ofhard wheat was 94 to 99 % depending on the wheat cultivar, feeding rate, and number of classification characteristics.N.S. Visen et al. (2002) compared the accuracy ofdifferent architectures of simple and specialist neuralnetworks in the classification of cereals. Morphologicaland chromatic characteristics of wheat, barley, oat, andrye kernels calculated using color images captured witha CCD camera were used as the input data. The grayfeatures: mean, median, mode, and standard deviationof gray-level values of the objects in the image \u2013 wereextracted and used as the input data. The best mean classification accuracy of 98 % was obtained using specialistprobabilistic neural networks.K. Goriewa-Duba et al. (2018) used the digital imagesof the kernels of six wheat species acquired with a flatbed CCD scanner to analyze the shape and color. They assessed the effect of grain colonization by endophytic fungion the color of the seed coat as well as estimated the wheatsubspecies with a high genetic variation. The images wereanalyzed using the ImageJ software to assess the shapecharacteristics, such as area, perimeter, Feret diameter,circularity, aspect ratio, roundness, and solidity. The colordescriptors included the mean values for the RGB, HSI,and L*a*b* channels. The principal component analysisof the kernels with different genotypes has shown thattheir color characteristics significantly contribute to thefirst variance component and are among the most important when classifying wheats into different genotypes.A. Alemu et al. (2020) analyzed the genome-wideassociations of nucleotide substitutions (GWAS) in thepopulation of 192 hard wheat (Triticum durum) genotypesfrom Ethiopia with grain shape and color traits. Grainlength and width were used to describe the kernel shapeand the mean values of the L*a*b* components to describe the color. In total, 11 quantitative trait loci (QTLs)were detected for the color characteristics; the locus forthe a* component resides on chromosome 2A; five locifor the b* component, on chromosomes 1B, 3A, 4B, 5A,and 7B; and five for the L* component, on chromosomes1A, 2A, 7A, and 7B.Another characteristic of the surface is its texture, whichis the image component that reflects the visual propertiesof these surfaces or objects (bumpiness and the presenceof regular patterns). The concept of texture is difficult toformalize since it to a considerable degree depends on thescale and has not any limitations on the basis of whichit is formed. A leaf in an image is an object and the foliage is a texture. It is possible to separate simple texturesthat are formed of ordered patterns or textons . A distinctive feature of a simple texture is itsregularity and repeated or partially reproduced elementson a certain surface or object. Other textures may have aconsiderably more complex structure.1, which is a second order histogram . The second order means that the matrix describes the distribution of intensities for the pairs of pixelsof an image with specific values. Thus, the combinationsof intensities for these pairs are taken into account. SeeV.G. Astafurov et al. (2014) for an example of computation of a GLCM. The GLCM is then used to extractthe statistics for the distribution of its elements, such asuniformity, homogeneity, moments of inertia, correlation,different mean values, variance, and entropy .The approaches more intricate as compared with thecolor analysis are used to describe textures since thetexture is characterized by mutual spatial arrangementof pixels with different intensities of their color components. Both the color and texture characteristics canbe determined utilizing statistical methods to assess theparameters of the histograms of the initial image, suchas, the mean, variance, asymmetry, and kurtosis. Forsimplicity, the images are described in the gray scale, i. e.,the description is reduced from pixel color characteristics (three components) to its total intensity alone , where x and y are the coordinates ofpixel). The gray level co-occurrence matrix (GLCM) is used for this purpose )https://vavilov.elpub.ru/jour/manager/files/SupplKomyshev_engl.pdfSupplementary Materials are available in the online version of the paper:The gray level run length matrix ) is constructed basedon the information about the run length of the pixels withequal intensity . These run lengths canbe specified by different levels of intensities and the traversal direction from one pixel to another. GLRM allowsfor computation of the statistics, such as inhomogeneityof gray level, inhomogeneity of run lengths, coefficient ofruns, entropy, inverse moment of short runs, moment oflong runs, and other characteristics .The third approach relies on the model-based interpretation of texture, for example, a method based onautoregressive model parameters in which the intensityof a pixel is predicted as the weighted sum of four intensities of the neighboring pixels . Several methods for texture description utilizeFourier, Gabor, or wavelet transform to characterize thespatial arrangement of the pixels of different intensitiesin the image from its frequency characteristic or waveletcomponents . In general, theabove briefed characteristics make it possible to formover a hundred of digital traits of image textures. Asa rule, only part of these characteristics is used in therelevant literature.An example of the use of texture characteristics inkernel analysis is the study by A. Pourreza et al. (2012).Images of nine wheat cultivars in a container illuminatedwith a fluorescent lamp were analyzed. The matrices(GLCM and GLRM) were computed for the gray scaleimages. Three additional characteristics were used; thesecharacteristics are determined by the difference betweenthe intensity of the central pixel from the intensities of theneighboring pixels in a 3\u00d73 matrix. The local similaritypatterns ) are calculated from the difference in the intensities between the central and neighboring pixels. If thedifference is below the SRR threshold, the LSP of theneighboring pixel is set equal to unity; otherwise, zero.A clockwise traversal of eight pixels gives a vector ofzeros and unities, which characterizes the correspondence of the intensity of the central pixel and all its neighbors.Another parameter in this work is local binary patterns),which were computed taking into account the weight coefficients of the neighboring pixels multiplied by LSP vectorcomponents. Finally, one more texture characteristics wasthe local similarity number ), which is the number of pixelswith an intensity similar to that of the central pixel in thesquare of N\u00d7N.Then, different statistics were calculated for the abovetextural features . Some of them were based on thehistogram gray level quantification (25 histogram bands).As was demonstrated, the textural features were mosteffective in classifying the cultivars as compared withthe other characteristics. Six of the nine cultivars wereidentified with a 100 % accuracy; two of the remainedcultivars were identified with 96 % accuracy. The useof the characteristics obtained from the LBP, LSP, andLSN matrices improved the classification accuracy ascompared with the earlier studies. In total, 54 % of the 50main textural features were selected from LBP, LSP, andLSN groups. The authors also conclude that the characteristics of feature distribution considerably contributedto identification of wheat cultivars.K. Sabanci et al. (2017) describes a machine visionsystem for distinguishing of kernels between the durumand bread wheats. The used visual characteristics includesize , color , and texture ; in addition, nine characteristics werecalculated from the main ones. In tests, the simplifiedclassifier identifies the grain type with an accuracy of99.46 % and sorts the wheat kernels with an accuracy of100 %. For training and verification, images of 200 wheatkernels (100 of bread wheat and 100 of durum wheat)were captured by a high-resolution camera.Spectrophotometers, spectrometers, and hyperspectralcameras are efficient and reliable tools for analysis andestimation of cereal kernels. However, they are expensive,especially those with a high resolution, both spatial andspectral. An alternative is digital cameras capturing highquality images with a high spatial and color resolution.Although the precieved spectrum of the currently available digital cameras is limited, the studies have shownthat they can be effectively used as a reliable and precisetool for solving manifold applied problems. A high spatialand color resolution of such cameras makes it possibleto analyze the textural characteristics of cereal kernels indetail. The textural characteristics are supplemented withcolor characteristics represented in different color models.Thus, the use of color and textural characteristics inthe analysis of digital images of cereal kernels allowfor an efficient resolution of several important problemsin their classification, sorting, and identification of diseases.The authors declare no conflict of interest.Adzhieva V.F., Babak O.G., Shoeva O.Yu., Kilchevsky A.V., Khlestkina E.K. Molecular-genetic mechanisms underlying fruit andseed coloration in plants. 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Identifying barleyvarieties by computer vision. Comput. Electron. Agric. 2015;110:1-8. DOI 10.1016/j.compag.2014.09.016.Szczypi\u0144ski P.M., Strzelecki M., Materka A., Klepaczko A.MaZda \u2013 a software package for image texture analysis. Comput. Methods Prog. Biomed. 2009;94(1):66-76. DOI 10.1016/j.cmpb.2008.08.005.Visen N.S., Paliwal J., Jayas D.S., White N.D.G. Ae \u2013 automationand emerging technologies: specialist neural networks for cereal grain classification. Biosyst. Eng. 2002;82(2):151-159. DOI10.1006/bioe.2002.0064.\u017dili\u0107 S., Serpen A., Ak\u0131ll\u0131o\u011flu G., G\u00f6kmen V., Van\u010detovi\u0107 J. Phenolic compounds, carotenoids, anthocyanins, and antioxidantcapacity of colored maize (Zea mays L.) kernels. J. Agric. FoodChem. 2012;60(5):1224-1231. DOI 10.1021/jf204367z."} +{"text": "The authors would like to correct the names and surnames of both authors of their previous paper as follo1,2,* and Yuri A. Mazei 2Costas A. Varotsos Therefore, to cite this paper please use the correct reference as follows:Int. J. Environ. Res. Public Health2019, 16 (20), 4015.Varotsos, C.A.; Mazei, Y.A. Future Temperature Extremes Will Be More Harmful: A New Critical Factor for Improved Forecasts."} +{"text": "Francisella tularensis subsp. mediasiatica is the least studied among the four F. tularensis subspecies. We present here the genome data of F. tularensis subsp. mediasiatica 240, isolated in the southern region of Kazakhstan. Francisella tularensis subsp. mediasiatica is the least studied among the four F. tularensis subspecies. We present here the genome data of F. tularensis subsp. mediasiatica 240, isolated in the southern region of Kazakhstan. Francisella tularensis. Currently, four subspecies of F. tularensis are recognized, differing in virulence and geographical distribution. F. tularensis subsp. tularensis (type A) is common in North America. It is the most virulent subspecies for humans. The two subtypes A.I and A.II also differ in virulence , but it was recently recovered in southern Siberia (The genetic diversity of Russia) , 6, and de novo assembled with Skesa v2.3.0 . Preparation of the sequencing libraries was carried out using the Nextera XT DNA library prep kit . Sequencing was performed using the MiSeq system with the MiSeq reagent kit v3 . In total, 780,074 sequencing reads were obtained. The reads were trimmed using Seqtk v1.3 (a v2.3.0 . The draP v4.11) , 11. Totbspecies . Strain type M.I .JABWGW000000000. The version described in this paper is the first version, JABWGW010000000. The raw data from BioProject PRJNA639508 were submitted to the NCBI SRA under experiment accession no. SRR12015651.This whole-genome shotgun project has been deposited in DDBJ/EMBL/GenBank under the accession no."} +{"text": "Juglans sigillata, or iron walnut, belonging to the order Juglandales, is an economically important tree species in Asia, especially in the Yunnan province of China. However, little research has been conducted on J. sigillata at the molecular level, which hinders understanding of its evolution, speciation, and synthesis of secondary metabolites, as well as its wide adaptability to its plateau environment. To address these issues, a high-quality reference genome of J. sigillata would be useful.J. sigillata, we first generated 38.0 Gb short reads and 66.31 Gb long reads using Illumina and Nanopore sequencing platforms, respectively. The sequencing data were assembled into a 536.50-Mb genome assembly with a contig N50 length of 4.31 Mb. Additionally, we applied BioNano technology to identify contacts among contigs, which were then used to assemble contigs into scaffolds, resulting in a genome assembly with scaffold N50 length of 16.43 Mb and contig N50 length of 4.34 Mb. To obtain a chromosome-level genome assembly, we constructed 1 Hi-C library and sequenced 79.97 Gb raw reads using the Illumina HiSeq platform. We anchored \u223c93% of the scaffold sequences into 16 chromosomes and evaluated the quality of our assembly using the high contact frequency heat map. Repetitive elements account for 50.06% of the genome, and 30,387 protein-coding genes were predicted from the genome, of which 99.8% have been functionally annotated. The genome-wide phylogenetic tree indicated an estimated divergence time between J. sigillata and Juglans regia of 49 million years ago on the basis of single-copy orthologous genes.To construct a high-quality reference genome for J. sigillata. It will lay a valuable foundation for future research on the genetic improvement of J. sigillata.We provide the first chromosome-level genome for Juglans regia) and the iron walnut (Juglans sigillata). J. regia is the globally cultivated well-known species, but J. sigillata (NCBI:txid224355) is still mostly unknown in Western scientific research despite being grown for its nuts in Yunnan province, China ) and A. thaliana (53\u201382 Mya) were used for fossil calibrations. The phylogenetic analysis showed that J. sigillata, J. curcas, and B. pendula diverged from a common ancestor \u223c69.41 Mya. The estimated divergence time of J. sigillata and J. regia was 49.49 Mya , with anigillata . Phyloge_011811) and cura_015945) . Phylogev 8.2.11 with the_014932) to estimJ. sigillata is an important cultivated tree that can be found growing on mountain slopes in southern China and in the Yunnan-Guizhou Plateau cx01 and [2016]cx03).F.C., D.N., and T.W. designed the study and contributed to the project coordination.; L.X., T.W., T.M., W.F., and R.D. collected the sample and extracted the genomic DNA. T.W., L.X., and T.M. performed research and/or analyzed data. T.W. wrote the manuscript. All authors reviewed the manuscript."} +{"text": "Phaseolus lunatus L.) is a member of subfamily Phaseolinae belonging to the family Leguminosae and an important source of plant proteins for the human diet. As we all know, lima beans have important economic value and great diversity. However, our knowledge of the chloroplast genome level of lima beans is limited.Lima bean , a large single-copy (LSC 80218\u2009bp) and a small single-copy region (SSC 17598\u2009bp). In total, 124 unique genes including 82 protein-coding genes, 34 tRNA genes, and 8 rRNA genes were identified in the The characteristics of the lima bean Cp genome was identified for the first time, these results will provide useful insights for species identification, evolutionary studies and molecular biology research.The online version contains supplementary material available at 10.1186/s12864-021-07467-8. Phaseolus lunatus L.) is one of five species domesticated within Phaseolus, together with common bean (P. vulgaris L.), scarlet runner bean (P. coccineus L.), tepary bean (P. acutifolius A. Gray) and year bean (P. polyanthus Greenm) [Lima bean ( Greenm) . Lima be Greenm) . Wild li Greenm) . Lima be Greenm) , 5. The Greenm) .C. arietinum [G. gracilis [L. japonica [C. tetragonoloba [G. max [V. radiate [P. vulgaris [infA, rpl22 and accD genes to the nucleus [rps12 and clpP introns [Chloroplasts, a place for plant photosynthesis, starch, fatty acids and amino acids biosynthesis, play an important role in the transfer and expression of genetic material . Chloroprietinum , G. gracgracilis , L. japojaponica , C. tetrgonoloba , G. max [G. max , V. radi radiate , and P. vulgaris . Leguminvulgaris , includivulgaris , 24, invvulgaris , 21, 25, nucleus \u201328 and l introns .trnL, rbcL and matK [matk gene and combining the characteristics of morphology, chemistry and chromosome number, a new classification system of six subfamilies was proposed, and the most complete leguminous phylogeny tree was constructed so far [Chloroplast DNA has been extensively used to taxonomy, phylogenetics and evolution of plants, due to its low substitution rates of nucleotide and relatively conserved structural variation of genomic \u201331. Phyland matK \u201334. Based so far . Howeverd so far , 36. DueP. lunatus. Here, we not only described the whole Cp genome sequence of P. lunatus and the characteristics of long repeats and SSRs, but also compared and analysed the Cp genome with other members of Leguminosae. It is expected that the results will help us to understand of the Cp genome of lima bean and provide markers for phylogenetic and genetic studies.Currently, there are no published studies of the Cp genome of lima bean. In this study, we applied a combination of de novo and reference-guides to assemble complete Cp genome sequence of G. max, P. vulgaris, V. unguiculata, G. sojasieb, V. faba and P. sativum were selected to Compare with lima bean , a large single copy and a small single copy and largest intron (2562\u2009bp), respectively. In the P. lunatus Cp genome, rps16 and rpl133 gene was found to be present as a pseudogene.Overall, 22 intron-containing genes (14 protein-coding genes and 8 tRNA genes) were found /matK, trnK-UUU, trnV-UAC, trnG-UCC and trnI-GAU.Two hundred ninety SSRs were identified in des Fig.\u00a0. Among tA. thaliana as a reference , while the ycf1 gene was only at the IRb/SSC border of P. vulgaris, C. cajan, G. max, and G. soja and the size varies among them.A comparison of the boundaries of the lima bean Cp genome was performed among the other six Leguminosae species: oja Fig.\u00a0. At the rpl23 of V. faba vs P. lunatusis, ndhD of C. cajan, rps18 of M. truncatula vs P. lunatusis, ndhD of G. max vs P. lunatusis, accD/ ycf2/ ndhD of P. vulgaris vs P. lunatusis, ndhB/ rps15/ ndhB of C. arietinum vs P. lunatusis, petL/ ycf2/ ndhD of V radiata vs P. lunatusis, petL/ ycf2 of V. unguiculata vs P. lunatusis and synonymous (Ks) substitutions and their ratios (Ka/Ks) have been used to assess the rate of gene divergence. The ratio of Ka/Ks\u2009<\u20091 represents purifying selection, while the ratio\u2009>\u20091 represents positive selection . In mostQuercus, which provide strong support for the deep phylogenetic relationship between subfamily tribes [P. vulgaris and P. lunatus are sister species, P. lunatus is more closely related to P. vulgaris, V. unguiculata and V. radiata. Consistent with the gene order results, they are all of subtribe Phaseolinae. The result is consistent with other phylogenies constructed by Cp genome containing representatives Phaseolinae genus [Genetic analysis of lima bean was performed using cytogenetic and moley tribes .. In ourae genus \u201370.P.lunatus was first sequenced on IlluminaNextera XT platforms. The size of genome, structure and organization of gene were shown to be conservative, which is similar to those reported Cp genomes of Leguminosae species. Sixty-one repeats and 290 SSRs were present in P. lunatus. These results are very useful for developing barcoding molecular markers. In comparison with other legume species, the Cp genome of lima bean shares a similar gene order and IR region borders with P. vulgaris, V. unguiculata and V. radiata. Phylogenetic analysis of 48 Leguminosae species shows that P. lunatus are more closely related to P. vulgaris, V. unguiculata and V. radiata. These results provide important information for the complete Cp genome of P. lunatus, which might be useful for further studies of evolution and phylogenetic.In this study, the complete Cp genome of P. vulgaris (NCBI ACCESSION NC_009259.1). The Cp genome of lima bean was submitted into GenBank .Fresh leaves were collected from lima bean plants grown on Huiyuan Vegetable Gardening Farm at Chongming Island . GenomicThe annotation of the Lima bean Cp genome was performed by blast v2.2.2 was compared with P. vulgaris (NC_009259), V. radiate (NC_013843) and V. unguiculata (NC_018051) in the Leguminosae tribe by mVISTA with the shuffle-LAGAN mode [P. lunatus was set as a reference.MUMmer was used to pair sequence alignment of the chloroplast genome . The chlGAN mode , 83. TheArabidopsis thaliana (NC_000932), C. cajan (KU729879), G. max (NC_007942), P. vulgaris (NC_009259), C. arietinum (NC_011163), V. radiate (NC_013843), G. soja (NC_022868), V. unguiculata (NC_018051) and M. truncatula (NC_003119).The gene order comparison was performed by MAUVE between P. lunatus was compared with the ten other species in Leguminosae tribe: G. max, C. cajan, C. arietinum, V. radiate, P. vulgaris, G. soja, V. unguiculata, P. sativum, V. faba and M. truncatula. The ten sequences was separately aligned by MAFFT v7.427 [In order to analyze non-synonymous (Ka) and synonymous (Ks) substitution rates and Ka/Ks ratio, T v7.427 , then thT v7.427 with theArabidopsis thaliana, all of which were down loaded from the NCBI except those of P. lunatus. The complete Cp genomes were aligned using MAFFT v7.427 [The phylogenetic analysis was conducted for lima bean, another 47 Leguminosae species, and one outgroup T v7.427 . RAxML vT v7.427 and MrBaT v7.427 was usedP. lunatus were uploaded to the NCBI database (https://www.ncbi.nlm.nih.gov/) with GenBank accession numbers . Other data can be obtained by contacting the corresponding author.The Cp genome of Additional file 1: Table S1. The number of genes in the P. lunatus Cp genome.Additional file 2: Table S2. The relative synonymous codon usage of the P. lunatus chloroplast genome.Additional file 3: Table S3. Repeated sequences of the P. lunatus chloroplast genome.Additional file 4: Table S4. Simple sequence repeats (SSRs) in the P. lunatus chloroplast genome."} +{"text": "X.J. Ni, Z.Q. Xu, H. Jin, S.L. Zheng, Y. Cai, and J.J. WangTransplantation Center, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, Chinawangjinjun5566@126.com>Correspondence: J.J. Wang: 300\u00a0ms) remain inducible at the end of the procedure are more likely to experience recurrence than those in whom no VT is inducible . In a reThe predictive capacity of immediate postablation PES was recently challenged by Frankel et al. , who havFor focal arrhythmias , activation and/or pace mapping are generally adequate guides for ablation (assuming the arrhythmia was present spontaneously or inducible prior to ablation). Assessment of efficacy is termination of VT, or elimination of PVCs, and subsequent noninducibility of VT or PVCs by catecholamine infusion or electrical stimulation that had reliably provoked episodes prior to ablation.Elimination of electrical excitability : TargetiElimination of LPs : EliminaElimination of LAVAs : LAVAs aDechanneling: Using this method, EAM is used to identify sites with high-frequency delayed (not necessarily \u201clate\u201d) potentials inscribed after a far-field component in sinus rhythm and targets those with relatively short intervals from potential entry sites into channels within scars that can participate in reentry. Endpoints of this \u201cdechanneling\u201d approach are the elimination of delayed potentials or reversal of the activation sequence of delayed potentials when recorded with multipolar catheters. VT-free outcomes were better when complete dechanneling could be affected .Substrate homogenization : This stCore isolation , 688: ThImaging-guided lesion assessment: Estimating the acute extent (particularly depth) of ablation-related damage, particularly in normal ventricular tissue, has been shown to be feasible with intracardiac ultrasound , CMR 10, near-inIdentification of a largely anatomically fixed substrate during baseline rhythm by pace mapping and by lFor patients with SHD in whom reentry is the primary VT mechanism, the effectiveness of ablation has usually been assessed by PES , with or without an adjunctive catecholamine infusion. In addition to these mapping tools, a variety of substrate-based strategies are currently in use for ablation for VA, each with their own procedural endpoints . A short description of these strategies is provided below , 1083. IAs noted, most strategies also use PES to assess for VT inducibility at the end of the procedure. It is important to note that the assessment of efficacy of these ablation strategies is predicated on the assumption that ablation lesions have permanent effects, which cannot be known.Some method of assessing success (prespecified endpoints) should be employed at the end of any ablation procedure for treating VA, insofar as possible (constrained by patient safety considerations). Scar-based reentrant VT usually incorporates PES using 3 extrastimuli at 2 drive CLs from 1 or more RV stimulation sites or at least as vigorous a stimulation protocol as was required to initiate arrhythmia prior to ablation, as well as achieving endpoints particular to whichever substrate-based ablation strategy is used.If a \u201cclinical\u201d (spontaneously occurring) VT remains inducible at the end of the procedure, the likelihood of postprocedure recurrence is high.Nonclinical VTs induced at the end of an ablation procedure have a recurrence rate during follow-up lower than persistently inducible clinical VTs but higher than if no VT is induced at the end of the ablation procedure. Clinicians should carefully consider the risks and benefits of targeting these nonclinical VTs, which entail longer procedure time and potential risk.It is reasonable to consider using NIPS 2\u20133\u00a0days after ablation to refine the prognosis . Several observations can be made based on available data:Although little has been written on postprocedural management of access sites specifically after catheter VT ablation, practices have been adapted by extrapolating results from other procedures requiring femoral venous or arterial access. Manual compression has been the standard of care for achievement of hemostasis after venous sheath removal. In randomized studies of other electrophysiology procedures comparing manual compression with temporary suture closures or a vascular closure device, comparable high rates of hemostasis had been achieved \u20131091. ExThe use of a temporary purse-string or figure-of-8 suture that can be removed after achieving hemostasis has been studied after venous access in other ablation procedures, such as for AF, in which procedures are routinely performed on uninterrupted anticoagulation and/or with large-bore catheters \u20131096. CoP\u2009<\u2009.001).Vascular closure device-based methods for venous closure have not been specifically studied for electrophysiology procedures \u20131099. OnWhen the writing committee was surveyed regarding venous access hemostasis, all the respondents used manual compression, approximately half (53%) used temporary figure-of-8 or purse-string sutures some of the time, and only 1 (6%) had used a vascular closure device. Given that venous access complications are driven primarily by insertion difficulties or concomitant arterial access, reduction in venous access complication outcomes might be best achieved with methods such as use of ultrasound at insertion, rather than by device- or suture-based methods.Arterial access after VT ablation is typically closed by manual compression or use of vascular closure devices, with comparably high success rates in achieving hemostasis. Though not specifically studied for VT ablation access closure, manual compression and vascular closure device use have been extensively studied for coronary or structural intervention procedures. Several systematic reviews and randomized trials have demonstrated shorter time to hemostasis, with little need for compression, shorter time to mobilization, and lower hematoma rates with use of vascular closure devices for arterial closure compared with manual compression, with no differences in vascular injury, thrombosis, or infection , 1101. EUse of vascular closure devices is generally avoided if the arteriotomy site is at or distal to the common femoral bifurcation, if contamination of the sheath is suspected, or if the posterior wall of the artery is suspected to have been punctured.When the writing committee was surveyed regarding arterial access hemostasis, 42% of the respondents had used manual compression 100% of the time, 29% had used temporary figure-of-8 or purse-string sutures 1%\u201325% of the time, and 67% had used a vascular closure device at least some of the time .If pericardial bleeding or cardiac tamponade has occurred during the procedure, the pericardial drain should ideally be left in place until there is minimal drainage output. This often requires observation in an intensive care unit and follow-up echocardiograms to assess for residual or loculation of fluid.P\u2009=\u2009.006), but not with intravenous or oral steroids . No difference was found in the occurrence of ECG findings for pericarditis with steroid therapy , and a nonsignificant reduced incidence of chest pain with ECG changes was found with steroid use .Epicardial access for VT ablation can be associated with postprocedure pericarditic pain and acute pericarditis. The use of steroids can reduce the incidence of postprocedure pericardial chest pain. In an animal model, triamcinolone 2\u00a0mg/kg significantly attenuated inflammation and postprocedure inflammatory adhesion formation after epicardial mapping and ablation . Della BAmong the writing committee members, 75% reported instilling steroids in the pericardial space after epicardial mapping/ablation, with 2 reporting this practice only after extensive epicardial ablation. Methylprednisolone, triamcinolone, or triamcinolone acetate were used by 40%\u201350%, and 9% had used dexamethasone. Only 8% instilled lidocaine into the pericardial space after ablation. In the absence of bleeding or tamponade, 38% leave a pericardial drain in place after epicardial ablation, usually for 8\u201324\u00a0h (89%) or\u2009>\u200924\u00a0h (11%).P\u2009=\u2009.012); however, ECG changes were noted less frequently .Whether or not to leave a pericardial drain in place after epicardial ablation can be a difficult decision and is based on concerns for late cardiac tamponade. However, Della Bella et al. noted thIn deciding whether to remove the pericardial drain, leaving a guidewire in the pericardial space after pericardial sheath removal and observing several minutes with intracardiac or transthoracic echo might be useful. This can exclude a \u201cthrough and through\u201d puncture of the RV, which will present with early significant hemorrhage after sheath removal.A pericardial drain may be left in place after epicardial ablation based on concerns for late cardiac tamponade. Della Bella et al. noted thIf the drain is left in place, longer duration can be associated with pericarditic chest pain (see above), and removal of the drain within 24\u00a0h might reduce the incidence of pericarditic chest pain.P\u2009=\u2009.091). Mahapatra et al. [P\u2009<\u2009.001), longer epicardial mapping time , RV puncture , and pericarditis pain score at 24\u00a0h . Prolonged drainage >24\u00a0h was not associated with AF incidence (P\u2009=\u2009.28). The occurrence of pericarditis renders anticoagulation decisions challenging; however, the use of steroids was not associated with a lower incidence of AF after epicardial VT ablation in these studies [P\u2009<\u2009.001 in the study by Mahapatra et al.) [The use of amiodarone might be reasonable to lower the risk of new-onset AF after epicardial VT ablation in patients with evidence of acute pericarditis. AF is reported to occur in 4.1%\u201319.5% \u20131105 of studies , 1105. I et al.) , 1105. NAntiplatelet therapy for less extensive endocardial VT ablation appears to be safe, with no significant bleeding nor thromboembolism risks. The Multicenter Thermocool Ventricular Tachycardia Ablation Trial has recommended antiplatelet therapy with aspirin 325\u00a0mg/day or anticoagulation with warfarin for 3\u00a0months after ablation, if ablation has been performed over an area with >3\u00a0cm between ablation sites . No procP\u2009=\u2009.06) and a shorter time to ambulation , with no differences in vascular access complications or thromboembolic events [Anticoagulation during left-sided VT ablation procedures is generally reversed for sheath removal, typically with protamine. In a retrospective cohort study of 158 patients undergoing RF catheter ablation, including 11 for VAs, 116 received protamine and 42 did not . No signc events .After extensive endocardial VT ablation, use of anticoagulation for a period of time has frequently been included as part of postprocedural practice, although there are no comparison studies. In the Multicenter Thermocool Ventricular Tachycardia Ablation Trial, antiplatelet therapy with aspirin 325\u00a0mg/day or anticoagulation with warfarin was administered for 3\u00a0months after ablation if ablation was performed over an area with >3\u00a0cm between ablation sites . No procHeparin bridging to oral anticoagulation or ambulation has been practiced but can be associated with a small risk of periprocedural bleeding after VT ablation. Among patients bridged with low-molecular-weight heparin to oral anticoagulation after VT ablation, Siontis et al. reportedAfter completion of VT ablation, patients are generally monitored on telemetry in the hospital for at least one day, and often longer for VT ablation in cases of SHD or heart failure. Patients who are hemodynamically unstable, who require hemodynamic or ventilator support, or who have had pericardial bleeding, cardiac tamponade, or a pericardial drain left in place are usually monitored and stabilized in an intensive care unit prior to transfer to a regular telemetry floor. Selected right-sided ablation patients may be discharged the same day, if stable, but patients with significant comorbidities, any instability, or left-sided VA ablation are typically monitored >24\u00a0h. Transtelephonic or CIED remote monitoring is often used to facilitate follow-up by 35%, 2\u00a0days by 52%, 3\u00a0days by 9%, and\u2009>\u20093\u00a0days by 4% of the writing committee members.Ablation of VAs is an invasive procedure that can be performed in patients with or without SHD. Despite new technologies and progress in techniques in recent years, complications are expected, especially in patients with more severe disease. In fact, the incidence of complications related to VT ablation is higher in patients with SHD than in idiopathic VT , 1109.P\u2009<\u2009.0001) [For the purpose of this document, major complications are defined as those that result in prolongation of hospital stay or another hospitalization, those that require additional intervention for treatment, and/or those that result in significant injury or death. All other complications, such as small hematomas not requiring intervention, are defined as minor. A recent meta-analysis reported major complication rates of 8%\u201310% after VT ablations . Slightl<\u2009.0001) .Interpretation of mortality in the setting of VT ablations in patients with SHD is difficult, given mortality can be a consequence of procedure-related complications but can also be related to procedural failure (incessant or recurrent VT). Table Periprocedural AHD, defined as sustained systolic hypotension despite optimized doses of vasopressors or requiring mechanical HS and procedure discontinuation, can occur in up to 11% of VT ablations in patients with SHD . The occSome measures can help to prevent these complications: close monitoring of fluid balance and diuresis, careful attention to hemodynamic status, optimization of medical status before ablation, avoidance of VT induction in higher-risk patients, preferring substrate mapping ablation, and avoidance of general anesthesia and certain drugs that can result in myocardial depression, including propofol. Use of a pLVAD, as discussed in Section P\u2009=\u2009.02). Other studies have failed to demonstrate the benefit of pLVAD, although the fact that these devices are selected for patients with more severe disease is a bias that is not possible to rule out [The pLVAD has been used in two scenarios: prophylactic, when higher-risk patients are identified, and for rescue during an acute complication. When used prophylactically, the pLVAD has been shown to prevent AHD and has a lower 30-day mortality (4.2% vs 58%). Mathuria et al. showed arule out , 1112. FNeurological complication is a rare but devastating event due to cerebral emboli or intracerebral hemorrhage that can occur with VA ablation, with a reported incidence of 0% to 2.7% , 614. ItA possible neurological complication is asymptomatic microembolism that results from thrombus formation, gas, tissue and/or fat dislodgement, and/or air embolism . The lonPericardial complication is the second most common reported complication of VT ablation in patients with SHD, being reported in 0% to 4.5% of procedures, although it can be higher in the subgroup of procedures in which pLVAD is used , 611. InAnother pericardial complication that can be found after VT ablation is pericarditis. It can be the sole complication or it might follow pericardial drainage due to cardiac tamponade. Symptoms of chest pain and low-grade fever, leukocytosis, and elevated C-reactive protein levels are commonly observed; diagnosis can be confirmed with ECG or echocardiogram. Pericarditis is also typically more frequent when an epicardial approach is used. Steroid administration in the pericardial space might be useful to prevent pericarditis . The authors concluded that when patients with VT and SHD have no VT or have only inducible nonclinical VT at the end of ablation or if they are too unstable to undergo final programmed stimulation during ablation, NIPS can be useful in the subsequent several days to further define the risk of VT recurrence, and if clinical VT is inducible during NIPS, to consider repeating VT catheter ablation due to the high risk of recurrence during follow-up were performed an average of 6\u00a0days after ablation on beta-blocker therapy in 210 consecutive patients. The positive and negative predictive values of PES for VT recurrence over 1\u00a0year of follow-up were 53% and 88%, respectively, and the negative predictive value was highest among patients with IHD and those with an LVEF >35% [Some advocate for routine PES, largely NIPS, shortly after VT catheter ablation and before discharging patients. However, there are no data from RCTs on the clinical usefulness of such a practice. Data on NIPS after VT catheter ablation were generated by two observational studies. In one such study, 132 patients with SHD underwent NIPS an average of 3\u00a0days after VT catheter ablation; 59 (44.7%) patients had no inducible VT, 49 (37.1%) had inducible nonclinical VT, and 24 (18.2%) had inducible clinical VT. At 1\u00a0year, patients with inducible clinical VT had a significantly lower VT-free survival than patients with no inducible VT found that LVADs improved health status in patients with heart failure who had low self-reported quality of life, but not in those with acceptable quality of life at the time of LVAD implantation . The meaAlthough a number of validated tools are available, the interpretation of findings can also be challenging. The VANISH trial assessed quality of life using 4 validated instruments . Among 1Assessing mortality after ablation is important. Although mortality is relatively high in many VA ablation populations, and VA recurrence has been associated with increased mortality, no trial has yet shown a mortality benefit from catheter ablation. Efforts to enroll a sufficient number of patients will be key to conclusively establishing the impact of ablation on mortality in a randomized trial , 1136. RCatheter ablation of VAs requires advanced skills in clinical cardiac electrophysiology. Physicians performing these procedures should be trained at electrophysiology programs with expertise in complex VA ablations and should meet the general and advanced training requirements for clinical cardiac electrophysiologists during training or with an experienced mentor if novel procedures and approaches have developed after training.2015 ACC COCATS 4: Task Force 11: Training in Arrhythmia Diagnosis and Management, Cardiac Pacing, and Electrophysiology report, the 2015 ACC/AHA/HRS Advanced Training Statement on Clinical Cardiology Electrophysiology, and the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias [2015 SPCTD/ACC/AAP/AHA Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology and the 2013 Recommendations for Advanced Fellowship Training in Clinical Pediatric and Congenital Electrophysiology: A Report from the Training and Credentialing Committee of the Pediatric and Congenital Electrophysiology Society [For adult electrophysiologists in the United States, these training competencies are outlined in the hythmias , 1139. F Society , 1141. A Society . Trainin2017 ACC/HRS Lifelong Learning Statement of Clinical Cardiac Electrophysiology Specialists [As the field of catheter ablation for VAs continues to evolve with introduction of new approaches, technology, and application in higher-risk and more complex patients , trainees and practicing operators specializing in these ablations are expected to continue to maintain their core and specialized competencies as outlined in the cialists . These pPhysicians performing catheter ablation for VAs should achieve proficiency in 6 core competency domains promulgated by the Accreditation Council of Graduate Medical Education and American Board of Medical Specialties. These 6 core competency domains include Medical Knowledge, Patient Care and Procedural Skills, Systems-Based Practices, Practice-Based Learning and Improvement, Professionalism, and Interpersonal and Communications Skills .A detailed understanding of cardiac anatomy is required, including the conduction system, the coronary arterial and venous systems, and anatomical variations due to underlying heart disease. Knowledge is necessary of the mechanisms and pathophysiology of VAs, with a particular focus on the relationship between these arrhythmias and acquired, inherited, or SHD; sympathetic and parasympathetic tone; and drugs. This understanding, along with proficiency in electrocardiographic interpretation, helps guide appropriate mapping and ablation approaches. In addition, knowledge of patient-specific factors such as disease type, severity, and comorbidities; procedural risks; and alternative therapies such as AADs, surgery, or device therapy should be used to guide appropriate patient selection.A comprehensive and structured approach to the clinical evaluation and management of patients with VAs undergoing catheter ablation is necessary across all settings (inpatient and outpatient) and time points . Trainees should demonstrate and maintain these proficiencies as pertains to their practice area of focus. A clear understanding of the various approaches and systems used and proficient demonstration of the skills to perform VA ablations are required. Additional advanced technical skills are needed for those seeking to perform epicardial ablations or ablations in CHD. Given patients undergoing complex VA ablations often have underlying medical conditions and comorbidities, recognition of the potential need for a multidisciplinary approach and coordination with other specialists will ensure optimal procedural outcomes.Complications can occur in catheter ablation procedures for VAs that can range from minimal to fatal. These can include vascular injury, thromboembolic events, cardiac tamponade, malignant VA including electrical storm, acute MI, and hemodynamic instability or collapse. A careful understanding of the potential procedural complications that might arise from either the patient\u2019s underlying medical conditions or the electrophysiology procedure itself is necessary. When appropriate, the use of a multidisciplinary team for the management of high-risk patients should be in place for prevention, prompt detection, timely intervention, and optimal management of complications. Functional systems should be in place to promptly care for patients in case of unanticipated complications.All trainees should continue to participate in lifelong learning to maintain and enhance skills and knowledge through self-assessment, regular literature review, updated practice guidelines, consensus document and appropriate use criteria, and attending appropriate scholarly meetings with a focus on VAs.On the basis of personal expertise and technical skills, practicing clinical cardiac electrophysiologists and trainees should practice within their scope as pertains to the specialized field of catheter ablation for VAs.Catheter ablation for VAs can be challenging due to increased procedural risk and complexity necessitating additional technical expertise. Practicing clinical cardiac electrophysiologists and trainees should engage patients, families, and interprofessional teams in a shared decision-making approach. These physicians must develop the skills to communicate and counsel effectively regarding the diagnosis, risks, and benefits of catheter ablation, and alternative management options.Awareness is rising of the detrimental effects on patients, the electrophysiology staff, and the operator of ionizing radiation during imaging. The use of low-frame rate fluoroscopy equipment, pre- and intraprocedural imaging with ICE, as well as 3D EAM, all contribute to reduce radiation exposure. Appropriate education of all personnel involved in the procedure on the risks and benefits of radiation is key for safer imaging. Societal recommendations have emphasized the importance of awareness of the principles of radiation safety and their implementation on a day-by-day basis while using radiation for medical imaging , 1146.High-risk patients include those with advanced heart failure, severe ventricular dysfunction, severe valvular dysfunction, prosthetic heart valves, CHD, inherited arrhythmia disorders, recent MI, recent stroke, chronic kidney disease, severe obstructive pulmonary disease, pulmonary hypertension, severe/morbid obesity, active oral anticoagulation, and advanced or pediatric age groups. Due to the potential risks associated with catheter ablation in close proximity to the coronary arteries and epicardial ablation, these procedures should be performed in a hospital-based electrophysiology lab with immediate availability of interventional cardiology or cardiothoracic surgical support .Interventional procedures, including coronary angiography, aortography, and deployment of percutaneous HS devices , requires advanced skills and should be performed by appropriately trained personnel.Epicardial ablation and mapping requires pericardial access that carries the risk of ventricular laceration or perforation. Inadvertent injury to the ventricle can result in life-threatening tamponade and hemodynamic collapse, which might require emergent surgical intervention via sternotomy. Immediate surgical intervention is critical and dependent on designated surgical backup (in-room or onsite with a clear notification protocol in place) and immediate access to an emergency surgical tray .Due to procedural complexities and patient factors, including underlying medical conditions and comorbidities, the use of anesthesia services provides optimal periprocedural patient care and additional expertise in the setting of life-threatening complications .VT ablation is a domain of specialized centers with high operational expertise. Within these centers, logistics for optimizing patient flow and referral are crucial. Therefore, many tertiary referral centers for VT ablation have established their network of regional referring centers to improve patient admission and early VT ablation. Few studies have documented their experience with this concept , 359.Conceptionally, \u201cVT networks\u201d centralize around highly experienced centers capable of all techniques associated with VT and electrical storm ablation, including epicardial ablation and HS. Discussion with a multidisciplinary team and immediate transfer should be possible. Electrophysiology staff should be available on a 24/7 basis. Although acute ablation, defined as ablation for rhythm stabilization within 8\u00a0h after onset, is rare, there is a potential need for catheter ablation on a 24/7 basis , 1147. HDedicated VT units have been established in some tertiary referral centers to expedite the transfer and management of patients with VT in a specialized intensive care unit. The optimal technical set-up of a dedicated VT unit has not been defined, but 12-lead ECG monitoring, online device telemetry, and intensive care unit facilities are helpful. The organization of VT units and networks would likely vary substantially across different countries according to the local health care delivery organization and resources. The ability to provide 24/7 catheter ablation might be useful for effective early rhythm stabilization, specifically in unstable patients with recurrent VA; however, comparisons with standards of care, including pharmacological suppression, HS, and neuromodulation, have not been made , 359. LeThe development of high-quality randomized trial evidence to establish an optimal therapy for VT has been challenging, despite the clinical importance of the question. Relatively few RCTs have been published comparing catheter ablation with noninterventional therapies. Recent consensus and guideline documents have consistently stressed the importance of further research in the field , 4, 156,Several randomized trials comparing catheter ablation with medical therapy are ongoing. The PARTITA trial (NCT01547208) is enrolling and following 586 patients with ICD implantation, and randomly allocating 176 who present with first ICD shocks to early catheter ablation vs withholding ablation until electrical storm occurs, with a primary composite endpoint of heart failure hospitalization and death from any cause. The PAUSE-SCD trial (NCT02848781) is enrolling 120 patients with ICM or NICM and randomly allocating them to ICD implant followed by catheter ablation or medical therapy with a composite endpoint of recurrent VT, cardiovascular re-hospitalization, and all-cause mortality. The IMPRESS TRIAL (NCT03531502) is enrolling 75 patients with cardiomyopathy who experienced a first ICD shock and is performing a NIPS procedure with a noninvasive mapping system . If the NIPS procedure is positive, then patients will be randomized to catheter ablation guided by noninvasive mapping or standard medical therapy with a primary endpoint of ICD shocks. The PREVENTIVE VT Trial (NCT03421834) is a randomized trial of 60 patients with a subset of ICM . Patients will be randomized to ICD alone or ICD plus catheter ablation, with an endpoint of time to first ICD therapy or VT-related hospitalization. The VANISH2 trial (NCT02830360) is enrolling 366 patients with prior MI who present with sustained monomorphic VT and is randomizing them to receive either catheter ablation or AAD therapy, with a primary composite endpoint of death, appropriate shock, or VT storm.Although observational studies have demonstrated an association between recurrent VAs and mortality , 1148, nFurther research is required to identify optimal methods for arrhythmia suppression and to understand the influences of each method on arrhythmia outcomes, as well as on cardiac function, symptoms, quality of life , cost-efAwareness of the importance of VAs as a frequent and potentially modifiable cause of death has led to increased development of novel methods to improve VT mapping (both inside and outside the body), VT treatment (inside and outside the body), and identification of an individual patient\u2019s status, along the spectrum of cardiac illness.Cardiac mapping has made an important advance with the development of tools that employ multiple small, closely spaced electrodes. These tools provide higher resolution mapping during sustained VT and sinus rhythm"} +{"text": "The objectives of our study were to survey the prevalence of genetic markers for Rickettsia spp., Ehrlichia spp., Anaplasma spp., Babesia spp., and Theileria spp. in Hyalomma anatolicum ticks collected in southwestern Tajikistan and to perform sequencing and phylogenetic analysis of fragments of the 16S rRNA gene and groESL operon from Ehrlichia spp. and fragments of the 18S rRNA gene of Theileria spp. detected in H. anatolicum ticks. Hyalomma anatolicum ticks collected in the Tursunzade and Rudaki districts of Tajikistan were tested for DNA of Rickettsia spp., Ehrlichia spp., Anaplasma spp., Babesia spp., and Theileria spp. by PCR with specific primers. The amplified fragments were sequenced and analyzed. DNA of Ehrlichia spp. (3.3 %) and Theileria spp. (3.3 %) was detected only in H. anatolicum ticks collected from the Rudaki district, and DNA of Ehrlichia spp. (0.7 %) was found in H. anatolicum ticks from the Tursunzade district. Sequence analysis of fragments of the 16S rRNA gene and groESL operon from Ehrlichia spp. revealed high similarity to Ehrlichia spp. The Tajik isolates of Theileria spp. were genotyped as Theileria annulata based on the analysis of 18S rRNA gene sequences. The phylogenetic analysis demonstrates that Ehrlichia spp. isolates are highly similar to Ehrlichia spp. circulating in China and Brazil. The isolate Tajikistan-5 is closely related to the putative novel species Ehrlichia mineirensis. The Tajik isolates of Theileria spp. were clustered with T. annulata isolates from Turkey, Iran, Pakistan, and China by phylogenetic analyses. Ixodid ticks transmit various pathogens to both humans andanimals in Asia .Twenty-three species of ixodid ticks have been described inthis region of Central Asia, with the predominant ixodid tickspecies being Hyalomma anatolicum Koch, 1844 . The Crimean-Congo hemorrhagic fever, Sindbis, andWad Medani viruses were previously detected in ixodid ticksin Tajikistan and other Asian countries . Hyalomma anatolicumticks are also known to transmit bacterial and parasiteinfections such as Lyme disease, babesiosis, piroplasmosis,theileriosis, and anaplasmosis . Theileria annulata is the causative agent of theileriosis indomestic animals, which is transmitted by 15 species of ixodidticks of the genus Hyalomma . Ehrlichia spp. are intracellularGram-negative bacteria, ecologically associated with ixodidticks and their animal hosts . The pathogenicityto domestic and wild animals, as well as to humans,has been demonstrated in Ehrlichia canis, E. chaffeensis,E. ewingii, E. muris and E. ruminantium . Currently, there are no publishedstudies on genetic markers and genotyping of Rickettsia spp.,Ehrlichia spp., Anaplasma spp., Babesia spp., and Theileriaspp. in H. anatolicum ticks in Tajikistan.The objectives of this study were to survey the prevalenceof genetic markers for these tick-borne infections in H. anatolicumticks collected in southwestern Tajikistan, and toperform sequence and phylogenetic analysis of Ehrlichia spp.and Theileria spp. detected in the ticks.Tick harvesting. Adult ticks were collected from domesticanimals in several villages of the Rudaki district and the Tursunzade district in southwestern Tajikistanin July 2009 . The ticks were transported and samplesfor analysis were prepared as described in . Tick species were identified by morphological examinationwith subsequent confirmation by PCR and sequencingof PCR products of a 16S rRNA fragment of the mitochondrialgenome of the ticks.PCR detection of genetic markers. DNA was isolatedfrom tick homogenates by phenol/chloroform extractionusing a commercial kit followingmanufacturer\u2019s instructions. It was kept at \u221220 \u00b0C until use.The genetic markers of Rickettsia spp., Ehrlichia spp., Anaplasmaspp., Babesia spp. and Theileria spp. in ticks weredetected by PCR with specific primers (see the Table). ThePCR fragments were purified using Wizard SV Gel and a PCRClean-Up System kit according to manufacturer\u2019sinstructions. All PCR fragments were sequencedin a 3130 Genetic Analyzer automated capillary sequencer(Applied Biosystems Inc.). DNA sequencing reactions wereperformed with BigDyeTerminator v3.1 Cycle SequencingKits . Both strands of each genefragment were directly sequenced; each sample was sequencedtwice. Precautions were taken at all steps of analysis to avoidcross-contamination among samples.Nucleotide sequences and phylogenetic analyses. DNAsequences were compared with sequences available in Gen-Bank using the Basic Local Alignment Search Tool (BLAST)on http://blast.ncbi.nlm.nih.gov. Evolutionary analyses wereconducted with MEGA5 software .Multisequence alignments were performed using ClustalX.For each analyzed gene a phylogram was constructed by themaximum likelihood method. Phylogenetic distances betweenhomologous sequences were calculated using Kimura\u2019s twoparametermodel. Confidence levels for individual branchesof the resulting tree were determined by bootstrap analysiswith 1000 replicates.Tick harvestingAdult H. anatolicum ticks were collected and grouped in 137 pools. Tick species wereidentified by sequencing a fragment of 16S rRNA mitochondrialgene for all pools. Two original variants of 16S rRNAmitochondrial gene fragment sequences found in these tickswere submitted to GenBank (accession numbers KP059123and KP059124). The nucleotide fragments showed 99.9 %similarity to the corresponding H. anatolicum sequences fromGenBank. These tick pools were tested by PCR for geneticmarkers of Rickettsia spp., Ehrlichia spp., Anaplasma spp.,Babesia spp., and Theileria spp. and other ticks were used forgenotyping. Of those ticks, 290 were collected in the Tursunzade district and 92 from the Rudaki district. The PCR tests forEhrlichia spp. and Theileria spp. were positive in the range0.7\u20133.3 %. The PCR tests for Rickettsia spp., Anaplasma spp.,and Babesia spp. were negative in all tick samples.Theileria identificationTheileria spp. was detected in 3.3 % ticks from Rudaki butnot in ticks from Tursunzade. The amplified PCR fragmentsof 18S rRNA (1090\u20131092 bp) were isolated and sequenced(GenBank accessions KM288517\u2013KM288519). The sequenceswere 100 % identical to isolates of Theileria annulatacirculating in Turkey (AY508463) and Iran , similar by 99.9 % to isolated from Pakistan(JQ743630) and China (EU073963) and by 99.7 % to isolatesfrom Spain (DQ287944). Phylogenetic analysis confirmed thatTheileria spp. isolates from the Rudaki district of Tajikistanbelonged to Th. annulata . The analysis of 18S rRNAgene fragment for three isolates of Th. annulata from southwesternTajikistan showed that all isolates were geneticallyidentical (100 % similarity).Ehrlichia identificationThe presence of Ehrlichia spp. has not been previously documentedin ticks and animals in Tajikistan. DNA of Ehrlichiaspp. was detected in five pools of H. anatolicum tickscollected in the Rudaki and Tursunzade districts. The infectionrates for Ehrlichia spp. were 3.3 % in Rudaki and 0.7 % inTursunzade. The fragments of the 16S rRNA gene (1291\u20131352 bp) and groESL operon (1248\u20131315 bp) were sequenced.The nucleotide sequences of 16S rRNA gene fragments werehighly conserved (99.5\u2013100 %) among studied isolates.The similarity levels of the studied 16S rRNA fragments toE. chaffeensis (CP007478), E. canis (KJ513197), and E. muris(NR121714) were 99.2, 99.2, and 99.3 %, respectively.The phylogenetic tree generated using Ehrlichia spp.groESL operon fragment sequences was markedly different from the tree based on 16S rRNA sequences . The16S rRNA gene fragment analysis (1140 nucleotides) showedthat all isolated Ehrlichia spp. were genetically close . The studied isolates grouped in the same branch ofthe phylogenetic tree as isolates from the Fujian province inSoutheastern China (DQ324547) and the Tibet AutonomousRegion of China (AF414399). The Tibetan isolate was groupedwith the E. canis branch, which is genetically close to the speciesE. chaffeensis, pathogenic for humans .We note that the Tajik isolates were most similar to Chineseisolates from regions of China that do not border Tajikistan.The phylogenetic tree generated using Ehrlichia spp. groESLoperon fragment sequences was markedly different fromthe tree based on 16S rRNA sequences . Thenucleotide sequences of groESL operon Ehrlichia spp. foundin Tajikistan are separated into three groups. Tajikistan 1and 2 isolates were closest to two isolates Ehrlichia spp. fromdifferent regions of China , Tajikistan 3 and 4 clusterwith a different Chinese isolate .Tajikistan 5 showed high similarity to Ehrlichia spp.(JX629806) isolated in Brazil from a Rhipicephalus microplustick . Tajikistan 5 has 13 nucleotide and2 amino acid substitutions in comparison to the Brazilianisolate. The American isolate was previously identified as anew species of Ehrlichia spp. named E. mineirensis. It causesclinical manifestations associated with ehrlichiosis in experimentallyinfected calf .Tajikistan 1\u20134 isolates clustered with Chinese isolates fromXinjiang and Yunnan Provinces. Xinjiang Province sharesborders with Tajikistan in southwestern China, unlike Yunnan.Tajikistan 5 isolate was the most genetically distinct fromother Ehrlichia spp. grouping with UFMG-EV and UFMTBVisolates from Brazil and BOV2010 isolate from Canada. We infer that Tajikistan 5 isolate belongs to theputative novel species of Ehrlichia spp. previously namedE. mineirensis.Hyalomma anatolicum ticks collected in Tajikistan were testedby PCR for markers of tick-borne bacterial and protozoaninfections. DNA of Ehrlichia spp. and Theileria spp. wasdetected in ticks collected from the Rudaki and Tursunzadedistricts. The infection rates for Ehrlichia spp. and Theileriaspp. DNA markers ranged within 0.7\u20133.3 % according toPCR. Fragments of the 16S rRNA gene and groESL operonfrom Ehrlichia spp. and of the 18S rRNA gene from Theileriaspp. were isolated and sequenced from H. anatolicumticks. Phylogenetic analysis demonstrated that Ehrlichia spp.isolates were highly similar to Ehrlichia spp. circulating inChina and Brazil. Isolate Tajikistan 5 was closely related tothe putative novel species E. mineirensis. The Tajik isolatesof Theileria spp. were genotyped as Theileria annulate, andfragments of the 18S rRNA gene from these isolates werehighly similar to the 18S rRNA gene of T. annulata isolatesfrom Turkey, Iran, Pakistan and China.The authors of this study have no commercial associations that might create a conflict of interest to the present work. All authorsare working in non-profit federal organizations. No competing financial interests exist.Aguiar D.M., Ziliani T.F., Zhang X., Melo A.L., Braga I.A., Witter R.A novel Ehrlichia genotype strain distinguished by the TRP36 genenaturally infects cattle in Brazil and causes clinical manifestationsassociated with ehrlichiosis. Ticks Tick Borne Dis. 2014;5(5):537-544. DOI 10.1016/j.ttbdis.2014.03.010.Begum F., Wisseman C.J., Casals J. Tick-borne viruses of West Pakistan:IV. Viruses similar to or identical with, Crimean hemorrhagicfever (Congo-Semunya), Wad Medani and Pak Argas 461 isolatedfrom ticks of the Changa Manga Forest, Lahore District, and ofHunza, Gilgit Agency, W. Pakistan. Am. J. Epidemiol. 1970;92(3):197-202.Cabezas-Cruz A., Valdes J.J., de la Fuente J. The glycoprotein TRP36of Ehrlichia sp. UFMG-EV and related cattle pathogen Ehrlichia sp.UFMT-BV evolved from a highly variable clade of E. canis underadaptive diversifying selection. Parasit. Vectors. 2014;7:584. DOI10.1186/s13071-014-0584-5.Cruz A.C., Zweygarth E., Ribeiro M.F., da Silveira J.A., de la Fuente J.,Grubhoffer L., Valdes J.J., Passos L.M. New species of Ehrlichiaisolated from Rhipicephalus (Boophilus) microplus shows an orthologof the E. canis major immunogenic glycoprotein gp36 with anew sequence of tandem repeats. Parasit. Vectors. 2012;11(5):291.DOI 10.1186/1756-3305-5-291.Gajadhar A.A., Lobanov V., Scandrett W.B., Campbell J., Al-AdhamiB. A novel Ehrlichia genotype detected in naturally infectedcattle in North America. Vet. Parasitol. 2010;173(3-4):324-329. DOI10.1016/j.vetpar.2010.06.034.Gres\u00edkova M., Sekeyova M., Tempera G., Guglielmino S., Castro A.Identification of a Sindbis virus strain isolated from Hyaloma marginatumticks in Sicily. Acta Virol. 1978;22(3):231-232.Parola P., Inokuma H., Camicas J.L., Brouqui P., Raoult D. Detectionand identification of spotted fever group Rickettsiae and Ehrlichiaein African ticks. Emerg. Infect. Dis. 2001;7(6):1014-1017. DOI10.3201/eid0706.010616.Petrova I.D., Kononova Iu.V., Chausov E.V., Shestopalov A.M., TishkovaF.Kh. Genetic variants of the Crimean-Congo hemorrhagic fevervirus circulating in endemic areas of Southern Tajikistan in 2009.Molecular Genetics, Microbiology, and Virology. 2013;(3):29-36.DOI 10.3103/S0891416813030063.Rar V.A., Livanova N.N., Panov V.V., Doroschenko E.K., PukhovskayaN.M., Vysochina N.P., Ivanov L.I. Genetic diversity of Anaplasmaand Ehrlichia in the Asian part of Russia. Ticks Tick BorneDis. 2010;1(1):57-65. DOI 10.1016/j.ttbdis.2010.01.002.Rar V.A., Maksimova T.G., Zakharenko L.P., Bolykhina S.A., DobrotvorskyA.K., Morozova O.V. Babesia DNA detection in canineblood and Dermacentor reticulatus ticks in southwestern Siberia,Russia. Vector-Borne Zoonotic Dis. 2005;5(3):285-287. DOI10.1089/vbz.2005.5.285.Rasulov I. Ticks status in Central Asia with a special emphasis on Uzbekistan.Parasitol. Res. 2007;101(Suppl.2):183-186.Robinson P.M. Theileriosis annulata and its transmission \u2013 a review.Trop. Anim. Health Prod. 1982;14(1):3-12.Roux V., Rydkina E., Eremeeva M., Raoult D. Citrate synthase genecomparison, a new tool for phylogenetic analysis, and its applicationfor the Rickettsiae. Int. J. Syst. Bacteriol. 1997;47(2):252-261. DOI10.1099/00207713-47-2-252.Sumner J.W., Nicholson W.L., Massung R.F. PCR amplification andcomparison of nucleotide sequences from the groESL heat shock operonof Ehrlichia species. J. Clin. Microbiol. 1997;35(8):2087-2092.Tamura K., Peterson D., Peterson N., Stecher G., Nei M., Kumar S.MEGA5: Molecular Evolutionary Genetics Analysis using maximumlikelihood, evolutionary distance, and maximum parsimonymethods. Mol. Biol. Evol. 2011;28(10):2731-2739. DOI 10.1093/molbev/msr121.Tishkova F.H., Belobrova E.A., Valikhodzhaeva M., Atkinson B.,Hewson R., Mullojonova M. Crimean-Congo hemorrhagic fever inTajikistan. Vector-Borne Zoonotic Dis. 2012;12(9):722-726. DOI10.1089/vbz.2011.0769.Wen B., Jian R., Zhang Y., Chen R. Simultaneous detection of Anaplasmamarginale and a new Ehrlichia species closely related toEhrlichia chaffeensis by sequence analyses of 16S ribosomal DNAin Boophilus microplus ticks from Tibet. J. Clin. Microbiol. 2002;40(9):3286-3290. DOI 10.1128/jcm.40.9.3286-3290.2002.Wu X.B., Na R.H., Wei S.S., Zhu J.S., Peng H.J. Distribution of tickbornediseases in China. Parasit. Vectors. 2013;6:119. DOI 10.1186/1756-3305-6-119."} +{"text": "The Middle East and North Africa represent a hyper arid region of the world. Humans in these regions have historically kept domestic livestock usually under harsh environmental circumstances. With recent human development, especially in the Middle East, the livestock industry has increased. Livestock is affected by ticks and tick-borne diseases on which there has been relatively few studies in this region. This review paper aims to (i) examine the diversity of ticks infesting livestock, (ii) assess the variety of pathogens in animals and humans, and (iii) to identify gaps in our understanding of tick biology and tick-borne disease transmission in the region. We found 55 tick species on livestock including camels, cows, goats and sheep, belonging to eight genera. Fifteen tick-borne pathogens were reported from livestock in the region. We highlight the magnitude of the tick problem in the region and evaluate the control efforts currently in place. We suggest that disease control and prevention could be achieved effectively through collaborative work among all stakeholders such as funding international research projects and establishing joint control programs to combat cross-border movement of ticks.Ornithodoros, Otobius, Amblyomma, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, and Rhipicephalus. In addition, 15 pathogens were recorded causing diseases of significance, with Crimean\u2013Congo hemorrhagic fever, theileriosis, babesiosis and anaplasmosis being widely distributed diseases in the region. In recent decades, there has been increasing trends in disease occurrence and movement associated with global movement of humans and global trade of animals. We suggest that disease control and prevention could be achieved effectively through good integration between public health, veterinary medicine and animal management, and ecological approaches. We recommend further research in the areas of tick ecology and tick born-disease transmission. Furthermore, we suggest evaluation and improvement of disease control policies in the region.Ticks are important vectors of an array of viral, bacterial and protozoan pathogens resulting in a wide range of animal and human diseases. There is limited information in the literature about tick species in the Middle East and North Africa (MENA) countries, even though they have suitable climate and vegetation for ticks and their hosts. We reviewed the occurrence of tick species and the pathogens they transmit from the MENA on published papers from 1901\u20132020. We found taxonomic records of 55 tick species infesting livestock representing the following eight genera: Ticks play a major role in transmitting infectious diseases. Emerging or re-emerging infectious diseases are important global problems of great concern to humans as well as to animal health, with many pathogens being able to infect multiple species ,2,3,4. WHyalomma alone causes enormous losses to the products arising from camels and other livestock across MENA region [The Arabian Peninsula is globally important as a source of energy, with vast oil and gas reserves that supply the energy demands for the entire world. Consequently, this area went through a vast development and changes. One of the side effects of this development has been the expansion of farming, particularly in the Arabian Peninsula, primarily to support the demands of the rising population . Camels,A region ,12,13. TThe aim of this review is to determine the tick-borne diseases and tick fauna prevailing in the Arab countries. A clear understanding of the abundance of tick species, their role as reservoirs and vectors of pathogens, as well as their geographical distribution, is pivotal in assessing the threat of disease outbreaks and controlling tick-borne diseases in the future.Review the diversity of ticks of livestock in the MENA region;Review the variety of pathogens transmitted by ticks, with especial emphasis on emerging or re-emerging tick-borne diseases;Identify gaps in the science of tick biology and tick-borne disease transmission in the region and provide recommendations on the management of ticks and tick-borne diseases in the region.The objectives of our study were to:We used Google Scholar, Science Direct, Scopus, Web of science and PubMed to collect the available research papers about ticks, tick-borne diseases and pathogens in Arab countries. We also searched for resources like reports that include tick species and tick-borne diseases in MENA countries. Two hundred and ninty four references have been used in this review paper. For each Arab country, we searched relevant literature by using the following keywords: \u2018the name of the country\u2019, \u2018ticks\u2019, \u2018tick species\u2019, \u2018tick-borne diseases\u2019, \u2018tick-borne pathogens\u2019, \u2018tick distribution\u2019, and \u2018livestock\u2019. The list of the ticks presented here includes almost all species on livestock from Arab world reported in published papers and books.Boophilus is replaced by Rhipicephalus and the species Hyalomma detritum is replaced by Hyalomma scupense, Hyalomma erythraeum is replaced by Hyalomma impeltatum.For nomenclature, we presented tick species names according to Guglielmone et al. . In thisThe Arab World consists of 22 countries in the MENA region: Algeria, Bahrain, Comoros, Djibouti, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libya, Mauritania, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates, and Yemen Figure . These s2, which comprises approximately 10.2% of the world\u2019s land mass. Out of this, 72.45% is located in Africa and 27.55% is located in Asia. This region comprises of two distinct parts, eastern and western. Generally, the Asian part of the Arab World is the Arab East while the African part is the Arab West [The Arab countries occupy 14,291,469 kmrab West ,19.Ninety percent of the region consists of arid, semi-arid and dry sub-humid areas. The area is characterized by harsh environment, limited water resources and arable lands. Throughout its long history these lands were the main source of grain and animal production ,18.izbas or local farm enclosures), where livestock holding areas are accessed by small mammals [About 80% of the world\u2019s cattle are infested with ticks. As a result, ticks are economically important ectoparasites of livestock. Ticks have negative effect on their vertebrate hosts due to blood feeding causing irritation, allergic dermal reactions, severe paralysis and tick toxicosis ,21. The mammals ,26.Ornithodoros and Otobius. Ornithodoros savignyi appears to be the most widespread, being recorded from most of the Middle East and into parts of North Africa. The hard ticks (Ixodidae) are represented by six genera of which H. impeltatum, H. dromedarii, R. annulatus and R. sanguineus are widely distributed in the MENA region. Among these, Hyalomma dromedarii is the most common tick with high prevalence due to large-scale camel farming.A total of 55 species of ticks in eight genera have been documented from livestock in North Africa and the Arabian Peninsula . The sofHyalomma and Rhipicephalus are the most common genera reported from livestock in almost all Arab countries. Hyalomma genus serves as the vector and reservoir of CCHF virus [Arab countries have a suitable habitat for ticks, however, taxonomic studies on tick species in most countries are very limited. The majority of taxonomic studies on ticks of the Arab world were generally focused on hard ticks. The maximum numbers of tick species from livestock are documented in Egypt, Sudan and Jordan . HyalommHF virus . In seveO. savignyi was reported in Wargla as a parasite of camels [R. bursa, R. turanicus, R. sanguineus, R. annulatus, I. ricinus, H. punctata, D. marginatus, H. scupense, H. impeltatum, H. marginatum, H. excavatum and H. lusitanicum [R. sanguineus, H. marginatum, H. scupense, R. bursa and R. turanicus [I. ricinus ticks were collected on cattle and identified, in North-eastern Algeria from December 2005 to March 2006 [H. dromedarii, H. rufipes, H. impeltatum, and H. impressum from camels in four regions of Southern Algeria. Whereas 11 species of ticks were recorded on domestic animals including H. punctata, D. marginatus, R. sanguineus, R. bursa, H. lusitanicum, H. scupense, H. excavatum, H. marginatum and I. ricinus during a study conducted in 2012, 2013 in Algeria [Hyalomma, Rhipicephalus, Dermacentor, Ixodes, Haemaphysalis and sixteen species consist of O. savignyi, R. bursa, R. turanicus, R. sanguineus, R. annulatus, I. ricinus, H. punctata, D. marginatus, H. dromedarii, H. rufipes, H. impressum, H. scupense, H. impeltatum, H. marginatum, H. excavatum and H. lusitanicum have been reported in Algeria from livestock according to our review were recorded from 521 collected ticks from sheep and cattle, and 13 species were identified; H. anatolicum, H. excavatum, H. asiaticum, H. marginatum, H. turanicum, H. scupense, H. impeltatum, R. turanicus, R. bursa, R. sanguineus, R. annulatus, R. kohlsi, and Hyalomma spp. The most encountered tick species was H. anatolicum in Hyalomma genus, R. turanicus in Rhipicephalus genus [Rhipicephalus, Hyalomma and Haemaphysalis are the main genera infesting livestock in Iraq [Ticks and tick-borne diseases constitute a major challenge for livestock health and production in Iraq . Iraq ha in Iraq ,92,93,94 in Iraq and are in Iraq . Twelve reported . A study of July . However in Iraq ,95,96,97R. kohlsi infesting sheep and goats. To define the tick fauna associated with domestic ungulate animals, El-Rabie et al. [H. parva, H. sulcata, R. sanguineus, R. bursa, R. kohlsi, R. annulatus, H. anatolicum, H. excavatum, H. marginatum, H. turanicum, H. scupense, H. impeltatum, H. dromedarii, and H. schulzei, representing three genera from native sheep, goats, camels and cattle. Haemaphysalis parva was the most common species among the 9545 specimens examined. Although Saliba et al. [Argas sp., Ornithodoros coniceps, O. erraticus, Ornithodoros tholozani, O. salahi, O. lahorensis and 17 ixodid species comprising of H. marginatum, H. rhipicephaloides, H. anatolicum, H. dromedarii, H. impeltatum, H. schulzei, H. scupense; R. sanguineus, R. turanicus, R. camicasi, R. bursa, H. erinacei, H. sulcata, H. parva, R. annulatus, R. kohlsi, and Ixodes sp. from East Jordan and the West Bank. No major attention was given to the tick\u2019s role in transmission of tick-borne pathogens. Twenty nine tick species from six genera including Haemaphysalis, Hyalomma, Rhipicephalus, Ixodes, Ornithodoros and Argas have been reported in Jordan. However, we have not included ticks from genus Argas in Few studies have been carried out on tick fauna ,98,99 ane et al. collectea et al. reportedH. dromedarii, H. impeltatum, H. schulzei. Further, four tick species including R. annulatus, H. anatolicum, H. marginatum, and R. sanguineus have been reported in 1999 in Kuwait in Disease Vector Ecology Profiles (DVEPs) that summarize unclassified literature on medically important arthropods, vertebrates and plants that may adversely affect in regions around the world [R. annulatus, H. dromedarii, H. impeltatum, H. schulzei, H. anatolicum, H. marginatum, and R. sanguineus have been documented from Kuwait are identified from human hosts [D. marginatus, H. anatolicum, H. schulzei, H. excavatum, H. parva, H. punctata, R. bursa, R. annulatus, R. sanguineus, and R. turanicus have been documented in the literature [O. tholozani (vector of relapsing fever) [R. sanguineus (vector of boutonneuse fever) [R. bursa, R. microplus, and R. decoloratus during 4 years survey in Libya on cattle, goats, sheep and camels. Though, R. bursa was originally reported from Libya [R. annulatus, R. microplus, R. decoloratus, R. sanguineus, R. evertsi, R. bursa, H. anatolicum, H. excavatum H. dromedarii, H. franchinii, H. impeltatum, H. rufipes, H. turanicum, and O. foleyi. Hyalomma, Rhipicephalus, Argas and Ornithodoros were the main genera. H. dromedarii was found abundant on camels, H. impeltatum on sheep and H. excavatum on cattle. H. dromedarii was the most abundant tick found overall [R. annulatus, R. microplus, R. decoloratus, R. sanguineus, R. evertsi, R. bursa, H. anatolicum, H. excavatum H. dromedarii, H. franchinii, H. impeltatum, H. rufipes, H. turanicum, O. tholozani and O. foleyi , O. tholg fever) and R. se fever) . Hoogstre fever) providede fever) identifiom Libya , this idom Libya . In 1992 overall . Fifteen. foleyi .Hyalomma and Rhipicephalus) and six species of ticks . Members of the genus Hyalomma, the principal vector of CCHF virus, were found in the same proportion as genus Rhipicephalus [A. variegatum, R. decoloratus, R. geigyi, H. dromedarii, H. impeltatum, H. impressum, H. rufipes, H. truncatum, and R. guilhoni [Ornithodoros sonrai and O. savignyi, and seven hard ticks H. excavatum, H. dromedarii, H. impeltatum, H. impressum, H. rufipes, H. nitidum and H. truncatum to document the climate change effects and distribution of ticks (Acari: Ixodida) in Senegal and Mauritania [H. dromedarii, H. impeltatum, H. excavatum, H. rufipes, R. sanguineus, R. evertsi, A. variegatum, R. decoloratus, R. geigyi, H. impressum, H. nitidum, H. truncatum, R. guilhoni, O. sonrai and O. savignyi and 15 ixodid species [H. dromedarii is the most prevalent species in Saudi Arabia [H. dromedarii and R. annulatus. Both tick species were collected from infested camels and cattle in the animals resting house at Hail region [Amblyomma, Haemaphysalis, Hyalomma and Rhipicephalus are the major genera comprising of seventeen species infesting livestock in Saudi Arabia . H. dromi Arabia . Al-Shaml region . Literati Arabia .Hyalomma, Amblyomma, and Rhipicephalus) and various species of ticks were identified from cattle, sheep, goat and camels. These include A. lepidum, A. variegatum, H. anatolicum, H. dromedarii, H. impeltatum, H. rufipes, H. impressum, H. truncatum, H. scupense, R. annulatus, R. decoloratus, R. evertsi, R. guilhoni, R. muhsamae, R. praetextatus, R. appendiculatus, R. simus and R. sanguineus [R. evertsi, R. decoloratus, R. sanguineus, R. turanicus, R. camicasi, R. annulatus, H. dromedarii, H. impeltatum, H. rufipes, H. anatolicum, H. truncatum, H. excavatum, A. variegatum, and A. lepidum [Sudan includes tropical forest, various types of forested and un-forested grasslands, semi-desert, and extreme desert. A large proportion of the ticks of tropical Africa occurs in Sudan. Among the large numbers of specimens studied from a wide variety of hosts, 63 tick species were listed infesting variety of domestic and wild animals including reptiles and birds . Whereasnguineus ,69,132. lepidum . OverallR. annulatus, H. anatolicum, H. excavatum, H. impeltatum, H. marginatum and R. sanguineus [The livestock sector has a significant impact on the Syria\u2019s economy. The central region is ideal for livestock farming with ample grazing lands. Grazing dairy cattle in pasture may acquire the infection during tick infestation . Six ticnguineus from UAE [H. scupense and H. rufipes are reported from camels in annual report of Central Veterinary Research Laboratory in UAE [In the UAE, there are limited studies on the ticks and tick-borne diseases of domestic animals including camels, cattle, sheep and goats. However, ticks are reported round the year from camels in recent findings , which a994\u20131995 . In 2010ar basis . In addifrom UAE . Recently in UAE . FifteenA. variegatum was more abundant on camels than on cattle and while cattle were infected with R. annulatus. Below 1500 m, R. kohlsi was more abundant on goats than on sheep and H. sulcata was found on sheep. Whereas H. dromedarii Koch was prevalent on livestock and H. excavatum was on camels. H. anatolicum, H. impeltatum and H. rufipes, H. arabica, R. evertsi, R. simus, R. sanguineus and O. savignyi ticks were also reported from various domestic animals. However in 1987, ten species of ticks were collected in the survey from the five hosts : A. variegatum, R. annulatus, R. kohlsi, H. excavatum, H. dromedarii, H. arabica, H. rufipes, R. evertsi, R. sanguineus, and R. simus [R. sanguineus collected from camels, cattle, sheep and goats were examined. Adult ticks of three species in the group were identified: R. camicasi, R. turanicus, and R. sanguineus s.s. Host relationships and ecological affinities were also analyzed [A. variegatum, R. annulatus, H. anatolicum, H. excavatum, H. dromedarii, H. impeltatum, H. rufipes, H. truncatum and R. sanguineus . While Indigenous sheep were randomly selected and examined for presence of ticks from 2010 to 2011. Seven species of ixodid ticks were identified including R. sanguineus, R. decoloratus, R. evertsi, H. marginatum, A. variegatum, R. annulatus, and H. sulcata [A. variegatum, R. annulatus, R. kohlsi, H. excavatum, H. dromedarii, H. impeltatum, H. anatolicum, H. arabica, H. truncatum, H. rufipes, R. evertsi, R. sanguineus, R. simus, R. decoloratus, H. marginatum, H. sulcata, R. camicasi, R. turanicus and O. savignyi followed by Yemen, Iraq, and Saudi Arabia , respectively . These fVector-borne zoonotic diseases have emerged or re-emerged in many geographical regions causing global health and economic problems that involve humans, pathogens, vectors and wildlife ,149. ManFrom the medical and veterinarian perspective, most of arthropod-borne infections can be associated with 116 tick species (32 argasid species and 84 ixodids). In addition, tick-borne diseases are common in the medical and veterinary clinical settings and a good surveillance is essential for the management of zoonosis and communicable diseases that are common to humans and animals .Argas, Ornithodoros and Otobius), as well as the hard-tick family, Ixodidae [Rickettsioses, tick-borne relapsing fever and Tularemia), and viral diseases ,161,162.ephalus) . Howeverhalitis) . The disFlavivirus. Camels and sheep are thought to be the natural hosts of ALKV [O. savignyi tick collected near Jeddah, Saudi Arabia [This virus is a recently described member of the tick-borne hemorrhagic fever group of the genus of ALKV . ALKV wai Arabia . In the i Arabia and Saudi Arabia ,204,240 Hyalomma, act as both reservoir and vector for this pathogen. Humans become infected by tick bites or through close contact with infected animals and humans [Hyalomma ticks were responsible for outbreaks in humans with high fatalities in the UAE, Oman, and Saudi Arabia [H. marginatum, H. rufipes, D. marginatus and Rhipicephalus rossicus [CCHF has been reported from more than 30 countries in Africa, Asia, South-East Europe, and the Middle East. The majority of human cases are workers in livestock industry, agriculture, slaughterhouses, and veterinary practice ,242. Thei Arabia ,172. CCHrossicus . CCHF dirossicus ,189,193.Flavivirus genus, and has been a growing public health concern in Europe and other parts of the world for the past 20 years [I. ricinus or I. persulcatus). The vertebrate hosts of I. ricinus and I. persulcatus, which may have TBEV, are wild and domestic animals. The virus prevalence in ticks can vary substantially within and among risk areas [This vector-borne disease is caused by the tick-borne encephalitis virus (TBEV) which belongs to 20 years . Ticks a20 years , humans 20 years . TBEV, tsk areas . Varioussk areas . TBE cassk areas . To datesk areas . TherefoAnaplasma species including A. marginale, A. centrale, A. bovis, and A. ovis for ruminants, and A. phagocytophilum for human and domestic animals [Anaplasma species including A. marginale, A. centrale, and A. bovis, from Tunisian cattle. Whereas, Awad et al. [A. marginale in cattle in northern Sudan and R. annulatus was the vector. Anaplasmosis has also been reported from other countries including Libya, Egypt, Iraq and Palestine , Pacific Coast tick fever, and Rickettsial pox. The Rickettsial pathogens are categorized into order Rickettsiales, which includes the family Rickettsiaceae and Anaplasmataceae [Rickettsia sp. in H. dromedarii ticks in the UAE. In addition, Demoncheaux et al. [Rickettsia aeschlimannii in H. dromedarii ticks from Tunisia [R. aeschlimannii in Hyalomma sp. from Egypt [Spotted fever mataceae ,254. Mosmataceae ,255. Al-mataceae recordedx et al. reported Tunisia and Loft Tunisia detectedom Egypt .Ixodes [B. burgdorferi sensu lato (s.l.) species complex including B. burgdorferi sensu stricto in North America [Borrelia afzelii, B. garinii, B. burgdorferi, Borrelia spielmanii and Borrelia bavariensis [I. scapularis ticks transmit B. burgdorferi to humans far more frequently than adult ticks. Efficient transmission of this spirochete requires a minimum of 24 to 48 h of tick attachment, at which time the nymph obviously is engorged with blood [B. burgdorferi, B. lusitaniae, B. garinii were reported in I. ricinus from Tunisia [B. burgdorferi was detected in ixodid ticks and soft ticks (O. savignyi) from Egypt in 2010 and 2014 [I. ricinus from other Middle East and North African countries [This is a zoonotic disease transmitted by hard ticks of the genus Ixodes ,257 and Ixodes . Globall America and fiveariensis . Nymphs th blood . There ath blood . Developth blood . Various Tunisia . Howeverand 2014 ,220 and ountries transmitted by ixodid ticks , which yields severe and mild infections in their vertebrate hosts [Theileria spp.) has been described in all livestock species and can cause significant economic losses to farmers [Theileria sp. has been reported from most of countries in Arab region including Egypt, Sudan, UAE, Mauritania, Saudi Arabia, Oman, Libya, Tunisia and Iraq [This is one of the most common tick-borne diseases, which have been studied in a wide range of livestock such as cattle, sheep, and goats. Few people studied theileriosis infected camels ,43,267. farmers . Theilerand Iraq ,229,238 Ticks are presented with a unique set of challenges and opportunities in the Arab region. The natural environment is arid and inhospitable, with pockets of habitat that periodically become productive . This isWith the development of effective vaccines, antibiotics and improved sanitation, infectious diseases were significantly reduced in the developed world in 1970s. However, the emergence of a series of new diseases and global spread of HIV/AIDS, led to infectious diseases being considered with increasing priority in health policy and political agendas ,274. MorTravel, trade and an altered attitude towards domestic animals, wildlife and nature influence vectors and pathogens distribution worldwide. The Middle East imports mostly goats, sheep and cattle from as far as Australia, China and Argentina, often using mixed transportation systems . Mixed tHyalomma species being imported into the USA, most-commonly on animals and animal products. Mertins and Schlater [Hyalomma on ostriches imported from Africa and Europe. However, Keirans and Durden [H. marginatum found on a human with travel history to Greece. A detailed travel history may be important for identification of ticks, as well as to assess the risk of vector-borne diseases.There are some scattered reports in the literature of Schlater documentd Durden reportedHyalomma is one of the most medically-important tick genera in the region. Species in this genus have been reported to transmit a variety of viral, bacterial, and parasitic diseases of medical and veterinary importance [Hyalomma spp. is CCHF virus. Sexually and transovarial transmission of CCHF virus was observed experimentally in H. truncatum [H. marginatum transmitted the CCHF in Russia, Turkey, and Crimean Peninsulas, H. anatolicum in Iran, Pakistan, Turkmenistan, and Tajikistan, H. asiaticum from Central Asia to China, and H. rufipes in Africa [R. conorii in H. rufipes and H. truncatum, R. aeschlimannii in H. marginatum, H. truncatum, and H. scupense, R. sibirica in H. asiaticum, H. excavatum, and H. truncatum, A. phagocytophilum in H. lusitanicum, and C. burnetii in H. scupense [Hyalomma species have also been implicated in tick paralysis in humans [portance . One of runcatum . In factruncatum . For insn Africa ,286,287.scupense ,287,288.n humans .H. anatolicum, H. impeltatum, H. dromedarii, R. sanguineus, and R. turanicus, were reported in the UAE before CCHF outbreak in UAE 1994\u20131995 [Thousands of livestock are imported annually from Arabian countries such as Sudan, Somalia and others such as Turkey, Argentina, Pakistan, Australia Iran and Uruguay in Saudi Arabia and UAE. Camel, sheep, goat and cattle production plays an integral part in the agricultural sector and contribute significantly to the food security of the country . Prior t994\u20131995 . Ticks c994\u20131995 . Results994\u20131995 .Little efforts have been made to put in place the policies to reduce risk. Determining and preventing the importation of infected hosts is widely used to stop importation of many domestic animal diseases of economic or public health importance. Some countries even endorse this principle for the movement of people, whereby they conduct surveillance for infected persons arriving at their international borders, particularly during human pandemics. The World Health Organization (WHO) provides guidance and training through its international health regulations (IHR). Rules and regulations for international trade including animals and their products are created and enforced by the WHO, for smooth flow of trade .Like the rest of the world, Arab countries are affected by climate change. Climate change is considered one of the many factors that play a role in tick abundance and distribution. Climate change impact (positive or negative) on the biology of ticks . Other factors such as habitat fragmentations, demographic modifications and other environmental changes may also be involved and complicating the processes. These factors may also facilitate the survival and establishment of colonies in regions where tick species were not prevalent before . The knoThe distribution and abundance of tick populations also depend on the interaction of large-scale climate influences, local scale microclimates, habitat characteristics (including tick predators) and host densities . MicroclOne health approach is used to tackle the zoonotic diseases by considering all components including environmental and ecological/wildlife as well as domestic animal and human factors . The sucWe found no published research papers on ticks and tick-borne pathogens in some Arab countries, despite the presence of animals in them. This could be interpreted in two ways. One possibility is that there might be no tick infestations in the country, which is very unlikely, knowing how prevalent the ticks are in the region. The second possibility might be that there is no research done on ticks, which could be the result of having different problems that need to be investigated and fixed. Whatever the case might be concerned authorities in each country should encourage tick-related research and provide necessary resources especially financial support.According to published papers, some tick species were common in neighboring countries that share joint borders. This calls for mutual collaboration among such countries to study and stop tick cross-border movement. In addition, the success of any tick control program in one country is always going to be reliant on good collaboration from the country on the other side of the border. Otherwise, it will serve as a tick reservoir from which ticks continue to cross into the border and reestablish infestations.In order to enhance tick control efforts, inter-country research projects should be established and supported by inter-country funding. This is very important for the management of tick species that are common in more than one country. Moreover, establishing a central collection of tick specimens and a repository for DNA and RNA samples extracted from different tick species in each country can facilitate and enhance the research on ticks. Consequently, tick management will be more successful over time. In addition, the collaboration among research teams in different countries will be more successful and effective.It is important to organize awareness creation workshops to ensure that the reporting of ticks and tick-borne pathogens is going to be a routine practice for people dealing with animals and that this is always going to be done in a proper and timely manner. This is because some animal care providers do not fully appreciate the importance of publishing research results or reporting the presence of tick and tick-borne pathogens as long as proper medicine and treatment are given to affected animals.Animal trade (import and export) regulations concerning border inspections of animals for the presence of ticks and tick-borne pathogens should be standardized among all Arab countries. This practice can eliminate, or at least minimize, any infiltration of ticks into a new country as a result of lenient inspection on some points of entry.There is a need for conducting comprehensive tick surveillances in each Arab country in order to know tick species and hosts. The results should be coupled with tick species mapping to determine the geographical distribution of tick infestations and the hot spots in each country. Latest mapping software and global positioning system data should be utilized.It is vital to establish a standard reference laboratory in each Arab country to identify tick-borne pathogens and to serve as an information resource and point of contact at the national, regional, and international levels.There is a need to encourage the use of cutting-edge research protocols for studying and identifying ticks and tick-borne pathogens with an emphasis on the use of molecular tools and next generation sequencing.Because the ixodid tick species reported in this review infests both animals and humans, they have veterinary and medical importance. The increase in tick-borne diseases has been attributed to a range of factors that include habitat fragmentation, changes in host communities, human travel and trade, and climate change. The ending of critical gaps in tick-borne diseases ecology research would significantly improve our ability to forecast the location and timing of hot spots of these infectious diseases and to target control efforts at the most important phase of the transmission cycle. Efficient prevention and control require the understanding of the local ecology and human behavior."} +{"text": "Scientific Reports 10.1038/s41598-017-15539-7, published online 10 November 2017Correction to: In the original version of this Article, Martin C. J. Bootsma, Perry J. van Genderen, Abraham Goorhuis, Martin Grobusch, Nicky Molhoek, Astrid M. L. Oude Lashof, Ellen E. Stobberingh & Henri A. Verbrugh were incorrectly listed as the COMBAT consortium.This error has now been corrected in the HTML and PDF versions of the Article, and in the accompanying supplementary material."} +{"text": "Aphids are a diverse family of crop pests. Aphids formed a complex relationship with intracellular bacteria.Depending on the region of study, the species composition of both aphids and their facultative endosymbiontsvaries. The aim of the work was to determine the occurrence and genetic diversity of Wolbachia, Spiroplasma andRickettsia symbionts in aphids collected in 2018\u20132019 in Moscow. For these purposes, 578 aphids from 32 collectionsites were tested by PCR using specific primers. At least 21 species of aphids from 14 genera and four families wereidentified by barcoding method, of which 11 species were infected with endosymbionts. Rickettsia was found in sixspecies, Wolbachia in two species, Spiroplasma in one species. The presence of Rickettsia in Impatientinum asiaticum,Myzus cerasi, Hyalopterus pruni, Eucallipterus tiliae, Chaitophorus tremulae and Wolbachia in Aphis pomi and C. tremulaehas been described for the first time. A double infection with Rickettsia and Spiroplasma was detected in a half ofpea aphid (Acyrthosiphon pisum) individuals. For the first time was found that six species of aphids are infected withRickettsia that are genetically different from previously known. It was first discovered that A. pomi is infected with twoWolbachia strains, one of which belongs to supergroup B and is genetically close to Wolbachia from C. tremulae. Thesecond Wolbachia strain from A. pomi belongs to the supergroup M, recently described in aphid species. Spiroplasma,which we observed in A. pisum, is genetically close to male killing Spiroplasma from aphids, ladybirds and moths. Bothmaternal inheritance and horizontal transmission are the pathways for the distribution of facultative endosymbioticbacteria in aphids. Aphids (Aphidoidea) are an insect superfamily from the orderHemiptera, which includes about 10 families or subfamiliesand about 5000 species. Aphids are widespread sap-feedingplant pests and can transmit at least 30 % of plant viruses. A complex interplay with intracellularbacteria also known as endosymbionts is commonlyobserved in aphids. Obligate associations with Buchneraaphidicola in aphids provide insect hosts with essential aminoacids absent in sap . Apart from that, thereare nine species of facultative symbionts of aphids coexisting with Buchnera, havingboth positive and negative effects on the hosts.Depending on the species, facultative intracellular symbioticbacteria may increase the resistance of aphids againstheat stress, parasitoid wasps, and fungal infections, participatein the synthesis of essential nutrients for the host withthe obligate symbiont, and facilitate the interaction of aphidswith plants that they feed on . However, ithas been shown that the Rickettsia bacteria have a negativeeffect on the fitness of the pea aphid Acyrthosiphon pisumand suppress the activity of Buchnera aphidicola . Spiroplasma bacteria in A. pisum shorten the lifespan of aphids and inhibit their reproduction , albeit have a (minor) protective effect against theparasitoid wasp Aphidius ervi . Therole of Wolbachia in aphids is not yet fully understood , but Wolbachiaendosymbionts in the Asian citrus psyllid Diaphorina citrirepress holin promoter activity in the alpha-proteobacteria\u2018Candidatus Liberibacter asiaticus\u2019, a citrus disease agent,therebykilling the bacteria and preventing the disease fromspreading .The present paper is dedicated to studying facultative endosymbiontsWolbachia, Spiroplasma, and Rickettsia in aphids.Wolbachia is the most common genus of symbiotic bacteriain insects, aphids not being an exception. Wolbachia infectionhas been recorded in 82 aphid species . Two genera of symbionts, Rickettsia and Spiroplasma , were recordedin A. pisum. Both Spiroplasma and Rickettsia were recordedin the cowpea (Vigna sinensis) aphid Aphis craccivora and the bean aphid Aphis fabae . Spiroplasma were also recorded in tropical aphids,specifically the citrus aphid Aphis citricidus and polyphagousAphis aurantii . Rickettsia wererecorded in the blackberry aphid Amphorophora rubi and the cotton aphid Aphis gossypii . The symbiont composition varies in aphid populationsaround the world . For instance,Wolbachia, Spiroplasma, and Rickettsia were not recordedamong facultative aphid symbionts in the Saratov Region,Russia .Symbiont infection research in aphids is of practical valuesince such studies are instrumental in developing new strategiesof controlling pathogen transmission in plants . Depending on the symbiont type, the information oninfection may be used for symbiont elimination or transinfectionwith a specific strain of bacteria to inhibit the vector\u2019sability for pathogen transmission.The goal of the present study was to investigate the incidenceand genetic diversity of the Wolbachia, Spiroplasma,and Rickettsia symbionts in the samples of aphids collectedin Moscow and the cities of Zvenigorod and Lyubertsy in theMoscow Region. Thus, 578 aphids from 32 collection siteswere PCR-tested using specific primers for Wolbachia, Spiroplasma,and Rickettsia. The taxonomic positions of aphid hostsand their symbionts were identified based on the sequencesof aphid and bacterial genes.Aphids were collected in July\u2013September 2018 and inMay 2019 in Moscow, Zvenigorod, and Lyubertsy (Table 1).A total of 32 aphid samples were collected from 17 plantspecies. The collected adult aphids were preserved in 96 %ethanol.Phenol-chloroform extraction was used to isolate total DNAfrom individual specimens . Amplificationreactions were performed in a 25-\u03bcl volume using theuniversal Encyclo Plus PCR kit followingthe manufacturer\u2019s protocol. All the reactions were performedusing the MiniAmp Plus thermocycler (Applied Biosystems).Aphid species were identified based on PCR using universalprimers LCO1490 and HCO2198 complementary to the 5\u2032 endof the mitochondrial cytochrome c oxidase subunit I gene(COI ), as described earlier .Symbionts were identified using specific primers as follows:RicF141 and RicR548 for the Rickettsia gltA gene, spi_f1 and spi_r3 for Spiroplasma16S rRNA , ftsZ-F1 andftsZ-R1 for the Wolbachia ftsZ gene . Theamplification procedure consisted of initial denaturation for4 min 30 sec at 94 \u00b0C followed by 36 amplification cycles asfollows: denaturation for 30 sec at 94 \u00b0C, annealing for 30 secat 59 \u00b0C , andextension for 40 sec (1 min for spi_f1 and spi_r3) at 72 \u00b0C.The PCR was finalized by an extension for 5 min at 72 \u00b0C.The PCR results were visualized by agarose gel electrophoresis(1.5 %). DNA fragments were eluted from gel using the DNA isolation kit for agarose gels Cleanup Mini under the manufacturer\u2019s instructions. The purifiedPCR products were sequenced by Evrogen (Moscow). Thenewly acquired COI gene sequences were registered in theGenBank database under accession numbers \u041c\u0422302332\u2013\u041c\u0422302357; gltA Rickettsia, under MT302358\u2013MT302364;ftsZ Wolbachia, under MT302365\u2013MT302368; and 16SSpiroplasma, under MT302369.http://www.barcodinglife.com/) and GenBank databases(https://blast.ncbi.nlm.nih.gov/Blast.cgi). Dendrograms wereplotted using the neighbor-joining method, Kimura evolutionarymodel, and 1000 bootstrap replications in the MEGA 6.06software . DNA sequences in the dendrogramswere provided with the GenBank and PubMLST (in thecase of Wolbachia) registration numbers on the right from theisolate name. The divergence between nucleotide sequenceswas calculated based on p-distances (per-site differences)usingthe MEGA 6.06 software .Sequence chromatograms were analyzed using theDNASTARLasergene 6 software . The newly obtained sequences were compared to thepreviously available ones using the Barcode of Life and Anoecia fulviabdominalis (96 %), respectively.The aphids collected represent four families as follows:Anoeciidae, Callaphididae, Chaitophoridae, and Aphididae. Evolutionary divergence values amount to 6\u201316 %between the aphid genera, 0.8\u20136.6 % between the Dysaphisspecies and 6.3 % between Aphis species. Two mtDNA haplotypeswere recorded in three species, namely Aphis pomi,Chaitophorus tremulae, and A. pisum . The differencesbetween COI haplotypes were 0.2 % in A. pomi, 0.6 %in C. tremulae, and 0.16 % in A. pisum.The apple aphid A. pomi, bird cherry-oat aphid Rhopalosiphumpadi, black cherry aphid Myzus cerasi, and Asian balsamaphid Impatientinum asiaticum were found in two or morecollection sites (see Table 1). Two aphid species were foundin the same plant species in the following cases: Hyalopteruspruni and M. cerasi in cherry trees, A. pomi and Dysaphisdevecta in apple trees, Anuraphis subterranea and Dysaphisaffinis in pear trees, with the last aphid species coexisting onthe leaves of the same tree (see Table 1). One aphid specieswas observed in different plant species in the following twocases: R. padi in bird cherry trees and wheat and A. pomi inapple trees and cotoneaster.Symbiotic bacterial infectionThe presence of Wolbachia, Spiroplasma, and Rickettsiawas analysed in 578 specimens of 21 aphid species and theinfections were detected in A. pisum (Spiroplasma and Rickettsia),I. asiaticum, M. cerasi, H. pruni, Eucallipterus tiliae(Rickettsia), A. pomi (Wolbachia), and Chaitophorus tremulae(Rickettsiaand Wolbachia) (Table 2). The C. tremulae specimensinfected with Rickettsia and Wolbachia had differentmtDNA haplotypes .Rickettsia were found in 84 aphid specimens representingsix species; Wolbachia, in 75 specimens of two species; andSpiroplasma, in 24 specimens of one species (see Table 2).Individual aphid specimens are typically infected by only onetype of symbiotic bacteria out of three. However, Rickettsia/Spiroplasma coinfection was recorded in A. pisum in 13 of28 individual specimens. In adult A. pisum specimens, 100 %were infected with one or two types of endosymbionts. Thepresence of Rickettsia in I. asiaticum, M. cerasi, H. pruni,E. tiliae, and C. tremulae and Wolbachia in A. pomi andC. tremulae has been described for the first time.Bacteria of the genus Rickettsia. Aphid Rickettsia wereclustered with the R. bellii group . Rickettsia in E. tiliaeand C. tremulae had species-specific gltA alleles. Rickettsiain A. pisum had two alleles, gltA1 and gltA2 (GenBank entries MT302358 and MT302359), differing in one nucleotidesubstitution.The gltA1 allele was observed in one A. pisumspecimen, and gltA2, in seven. The gltA1 allele was also observedin Rickettsia from H. pruni, and gltA2, in Rickettsiafrom I. asiaticum and M. cerasi. The gltA1 allele was identicalto the Rickettsia DNA from A. pisum strain PAR (the USA)registered in GenBank as FJ666756 . The gltA2allele has been discovered for the first time. The newly obtainedRickettsia DNA sequences differed significantly frombacterial DNA in Sitobion miscanthi aphids (HQ645973)genetically close to R. bellii . The evolutionarydivergence value between the R. bellii group and Rickettsiagroup in the present paper amounted to 8.2 %, which greatlyexceeded the divergence between, for example, the R. typhiand R. prowazekii species (2 %).Bacteria of the genus Wolbachia. Within the genus Wolbachia,there are 16 phylogenetic supergroups . Wolbachia from Aphis pomi #1 (MT302366) and#3 (MT302367) were clustered with supergroup \u041c bacteria,and Wolbachia from Chaitophorus tremulae (MT302365)and A. pomi #2 (MT302368), with supergroup \u0412 . TheDNA differences in the ftsZ gene sequence of Wolbachia fromA. pomi #2 (MT302368) and #1 (MT302366) amounted to14.3 % (67 of 466 bp). At the same time, the ftsZ gene alleleof Wolbachia from A. pomi #2 (MT302368) had only threedifferent substitutions if compared tothe Wolbachia DNA from the Aspen leaf aphid Chaitophorustremulae (MT302365).The sample of A. pomi infected with group B Wolbachiawas collected from cotoneaster, and the samples of A. pomiinfected with group M Wolbachia, from cotoneaster and appletrees (see Table 1). The distance between the collection sites,where A. pomi were collected from the same plant species butinfected with different Wolbachia strains, was over 20 km.At the same time, the distance between the collection sites,where A. pomi were collected from different plant speciesbut infected with the same Wolbachia strain, did not exceed4 km (see Table 1).Bacteria of the genus Spiroplasma. Spiroplasma observedin A. pisum were clustered with the bacteria encounteredin A. pisum in Japan (AB048263), Britain , and A. craccivora from the USA (KF362032). Variation of 16S rRNA genes of Spiroplasma inaphids from A. pisum collected in geographically separatedsites amounted to 0.3\u20130.6 % (5\u20138 nucleotide substitutions per974 bp). All of them are included in the Spiroplasma ixodetisclade. The latter also had the symbionts of other insects, suchas lady beetles Anisosticta novemdecimpunctata (\u0410\u041c087471) and the moth Ostrinia zaguliaevi (\u0410\u0412542740). Nucleotidevariation within this clade did not exceed 0.6 %. However,nucleotide variation between the clades of the genus Spiroplasmareached 10\u201316 %.The study has demonstrated that at least 21 aphid species wererepresented in the 32 samples investigated. Most aphid speciesstudied (18 of 21) belong to the family Aphididae, whilethe families Anoeciidae, Callaphididae, and Chaitophoridaeare each represented by one species. Two species were notconfined to their plant hosts, whereas 19 aphid species wereencountered on particular plant species.For the first time, Rickettsia infection has been observed inI. asiaticum, M. cerasi, H. pruni, E. tiliae, and C. tremulae, andWolbachia infection, in A. pomi and C. tremulae. As opposedto other studies , aphid speciescollected in Moscow in the present research were mostlyinfected by Rickettsia rather than Wolbachia. The specimensof the Aspen leaf aphid C. tremulae infected with Rickettsiaand Wolbachia have different mtDNA haplotypes, althoughit has yet to be studied in a larger number of samples whethercytoplasmic components are inherited together in this particularaphid species. Rickettsia and Spiroplasma coinfectionwas recorded in half of the specimens of the green pea aphidA. pisum. Many authors have already noted the presence ofRickettsia and Spiroplasma among the A. pisum facultativesymbionts in Europe , the USA , and Japan . Among28 A. pisum specimens in the sample from Zvenigorod, infectionrates were 61 % (Rickettsia) and 86 % (Spiroplasma), which is several times as large as the previous figures, 8 and3 % in 119 isofemale lines from 81 populations in Japan , 48 and 9 % among 318 specimens in theUSA , 4 and 22 % in 30 lines , 23 and 27 % in samples collected from eightlegume species from England and Germany . It is possible that these high bacterial infection ratesonly existed for a short period, since both Spiroplasma andRickettsia reduce the life span of aphids and inhibit their fertility.According to our observations, prolonged laboratory cultivationof A. pisum previously resulted in a loss of Spiroplasmasymbiotic bacteria.Aphid Rickettsia in our collections form a separate cluster. Itwas shown earlier that Rickettsia from A. pisum were attributedto the R. bellii group based on a comparison of four bacterialgenes . Other bacterial genes in differentaphid species are to be studied to find out whether they forma separate species within the genus Rickettsia. The bacterialgroup R. bellii is the basal group of Rickettsia formed beforethe pathogenic spotted fever group and murine typhus group. Four genetically different alleles of theRickettsia gltA gene were discovered in the six aphid speciesstudied, two of them encountered in A. pisum. One allele(MT302359) was observed in specimens from three aphidgenera, another one (MT302358), in two genera, and the tworemaining species had unique allelic variants of symbionts(MT302363-64). Thus, we may assume that different aphidspecies were infected with Rickettsia independently.Spiroplasma discovered in A. pisum based on DNA analysisof the 16S rRNA gene is clustered with the bacteria previouslyobserved in A. pisum and A. craccivora. It has been shownthat Spiroplasma in A. pisum cause male offspring deathsat early larval stages, i. e. androcide or male-killing , and are genetically close to the Spiroplasmathat caused androcide in aphid predators, i. e. lady beetles and moths . Allthese bacteria are a part of the Spiroplasma ixodetis group.S. ixodetis is an endosymbiont described in ticks, but it is alsocommon in other arthropods. Phylogenetic studies have shownthat S. ixodetis strains are subjected to multiple horizontaltransfers between ticks and other arthropods including aphids.The present study has discovered Wolbachia infection inthe apple aphid A. pomi for the first time. Wolbachia wasfound in 100 % of A. pomi specimens in our collections, eventhough this symbiont had not been observed in this aphid speciesfrom Greece earlier . The appleaphid A. pomi from three collection sites in Moscow were infected with two Wolbachia strains,one attributed to supergroup \u0412 and another, to supergroup \u041c, which had been described as prevalent in theaphid species of Spain, Portugal, Greece, Israel, and Iran, China , and theAzores . Since the data shows the group\u2019slow genetic variation, one might assume that it emerged quiterecently and spread rapidly across aphid populations .The results allow us to assume that infection of A. pomi witha specific Wolbachia strain is not linked to the plant host spespecies,but rather to its habitat. The noteworthy fact of discoveringallelic variants of the Wolbachia ftsZ gene with only slightdifferences in various aphid species (A. pomi and C. tremulae)may imply the possibility of bacterial gene exchange duringhorizontal transfers of Wolbachia among insects, for example,through parasites or plants. This hypothesis is corroborated bythe discovery of closely related alleles of Wolbachia genes inother unrelated insects . Symbiont DNA diversity is persuasive evidenceof maternal inheritance and horizontal transfer being the keydistribution mechanisms of facultative bacteria in aphids.While laboratory research results provide an increasinglybetter understanding of the role of aphid symbionts, data onsymbiont distribution in aphid populations in natural ecosystemsare still insufficient. The present paper provides the firstreport on the genetic diversity of bacterial endosymbiontsin previously understudied aphid species. Aphid populationscreening in Moscow and the Moscow Region made it possibleto newly identify Rickettsia infection genetically differentfrom infection with R. bellii, to which aphid symbionts aretypically attributed, in six aphid species .Whether these bacteria should be considered a new species isto be decided by studying a larger number of Rickettsia alleles.An apple aphid A. pomi infection with two Wolbachia strainshas been discovered for the first time, one being in the supergroupB strain, which is genetically close to Wolbachia fromAspen leaf aphids. The second Wolbachia strain from A. pomibelongs to supergroup \u041c. Regardless of the strain, 100 % ofA. pomi specimens in the present study were infected withWolbachia, and we thus may assume that there is a selectionmechanism of infected specimens in place, which involves thereproductive manipulations discovered in Spiroplasma fromA. pisum . However, most aphid generationsare asexual, and if symbiont infections are maintainedin natural aphid populations by reproductive effects, then thisreproductive phenotype has to be of great value for the insecthost. The obvious advantage of androcide is that it preventsinbreeding in the aphid population . Asfor now, it is unclear whether these advantages outweigh thepossible side effects of symbiont infection during the asexualphase of the lifecycle. The positive effect, i. e. resistanceagainst natural enemies , seems to be the key driver of an increasingincidence of Wolbachia, Spiroplasma, and Rickettsia facultativeendosymbionts in aphid populations.The authors declare no conflict of interest.Augustinos A.A., Santos-Garcia D., Dionyssopoulou E., Moreira M.,Papapanagiotou A., Scarvelakis M., Doudoumis V., Ramos S.,Aguiar A.F., Borges P.A.V., Khadem M., Latorre A., Tsiamis G.,Bourtzis K. 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DOI10.1111/een.12281."} +{"text": "Dear Editor,n = 5) and gene panel sequencing (n = 35) results indicate that, most driver mutations associated with CRC, such as APC, KRAS, and PIK3CA, are mutated at lower rates in SRCC is a rare subtype of colorectal cancer (CRC) characterized histologically by the accumulation of mucins in the cytoplasm and displacement of nuclei to the cellular periphery, accounting for about 1% CRC of signet-ring cells. To gain a better understanding of genomic alterations in SRCC, we performed WES on these SRCCs and paired normal tissues (Tables S2 and S3). WES data of AC and MAC from the Cancer Genome Atlas (TCGA) were analyzed for comparison (Tables S4 and S5) TCGA, .POLE mutation or microsatellite instability-high) were considered as hypermutated , RNF43 (34.5%), MUC16 (31.0%), TTN (31.0%), PCDH17 (27.6%), KMT2D (24.1%), and SMAD4 (20.7%) as most frequently mutated genes and TGF-\u03b2 pathways were mutated at similar frequencies cross CRC subtypes, however the mutation burden in WNT, MAPK, and PI3K pathways were dramatically lower in SRCC, suggesting subtype-specific molecular signatures . The overall mutation rate of SRCC is 9.65/Mb (medium mutation rate is 3/Mb), and 3 cases and MAC (~70%) enriched at the N-terminus, regardless of mutation burden , whereas AC and MAC prefer APC mutation. In addition, DKK4 amplification and mutations on FZD10, AMER1, and AXIN2 were identified in SRCCs, which may also contribute to \u03b2-catenin activation in the absence of RNF43 and APC mutation .The WNT pathway is instrumental to intestinal homeostasis and the initiation of AC TCGA, , whereas%) TCGA, . Interesft) Fig.\u00a0. Both APft) Fig.\u00a0. Almost PIK3CA, PTEN, IRS2 were enriched in AC and MAC, whereas almost absent in SRCC; and KRAS mutation rate in SRCC was about 4-fold lower than that in AC or MAC (Table S13). The gene expression pattern of SRCC was drastically different from that of AC and MAC , the differentially expressed genes in SRCC (compared to AC) were negatively correlated with E2F signaling, MTOR signaling, and metabolism Figs.\u00a0.LGR5, SOX9, AXIN2, and MSI1, were expressed at lower levels in SRCC compared to those in AC (Table S14). The relatively lower expression of LGR5 and SOX9 in SRCC was further verified by quantitative PCR, in situ hybridization, or IHC , the National key R&D program of China (2018YFA0800304) to F.X. Y., Science and Technology Commission of Shanghai Municipality , Shanghai Municipal Commission of Health and Family Planning (2017BR018 to F.X. Y.) and Shanghai Sailing Program (19YF1409500 to Y. L.). We would like to thank Dr. Kang Chen for proofreading of this manuscript.G. H., J. P., and F.X. Y. designed the experiments. Specimens and clinical data collection: Y. Li, R. W., S. C., and J. P. prepared specimens and collected clinical data. H. W., and F.X. Y. performed WES. D. Z., D. D., and Y. Liu processed WES data. S. H., J. P., and F.X. Y. performed RNAseq and analysis. Y. Li, J. L., X. W., Y. W., G. F., C. F., X. M., M. P., Q. G., X. X., X. H., Y. Z., and S. M. performed experiments. Y. Li, J. L., J. G., L. Z., Q. H., and F.X. Y. analyzed data. Y. Li, J. L., L. Z., Q. H., and F.X. Y. wrote the manuscript.All authors declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by the any of the authors.Supplementary material 1 (PDF 3195 kb)Supplementary material 2 (XLSX 8494 kb)Below is the link to the electronic supplementary material."} +{"text": "Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.Antibiotic resistance is the major reason for Helicobacter pylori is a Gram-negative, flagellated, spiral-shaped bacterium that penetrates the mucosal layer of the upper gastrointestinal tract [H. pylori relieves peptic ulcer disease and reduces the risk of gastric cancer [H. pylori are gradually changing, and the indications are expanding [H. pylori eradication is increasing.al tract ,2. It isal tract ,4 and real tract . Eradicac cancer ,7. Globaxpanding ,9,10. InH. pylori infection and is now the standard worldwide [H. pylori treatment [H. pylori is particularly serious; clarithromycin-containing regimens are no longer appropriate because of the <80% eradication rate [H. pylori eradication are limited , an increase in antibiotic resistance is a major problem. Therefore, the exclusion of clarithromycin is not enough to prevent antibiotic resistance of H. pylori. In the 1990s, triple therapy, consisting of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin, was introduced for the eradication of orldwide ,12. Sincorldwide ,14. The orldwide . Antibioreatment ,16. Resiion rate . The ratH. pylori treatment regimen [H. pylori [H. pylori eradication strategy according to the results of antibacterial susceptibility testing (AST). However, the possibility of false negatives and applicability in all medical institutions are problems [H. pylori regimens, which overcome antibiotic resistance and strategies that can be applied in practice. Current guidelines emphasize the importance of the local prevalence of antibiotic resistance when selecting a suitable regimen ,9,10. In. pylori . However. pylori . In addi. pylori . Therefoproblems ,20. We rH. pylori culture is intricate and time-consuming. Examination of the clarithromycin sensitivity of H. pylori improves the eradication rate [H. pylori treatment based on AST, such as a diagnostic test for clarithromycin resistance is useful. However, in some cases, the eradication rate is < 100%. This is because the point mutations other than A2142G or A2143G lead to unreliable results, e.g., A2142C, A2115G, G2142T, A2142T, and T2182C [Bacterial culture is typically performed before selecting an antibiotic, but ion rate ,22. Gerrion rate . Therefod T2182C ,24. In ad T2182C ,26,27,28d T2182C . The difH. pylori therapy based on AST results significantly improves the eradication rate. However, unlike other regimens, few studies have evaluated AST-based first-line regimens. The intention-to-treat (ITT) eradication rate for a first-line regimen is >90% [H. pylori eradication rate (90.2% by ITT and 97.8% by per-protocol (PP) analyses) [H. pylori resistant to two antibiotics [H. pylori is increasing, this is an encouraging finding. Culture-based H. pylori first-line eradication regimens show an excellent therapeutic effect, even in regions with a high rate of antimicrobial resistance [H. pylori in a region with a high rate of antimicrobial resistance had a high eradication rate [ is >90% ,31,32. I is >90% ,31. In aibiotics . Becausesistance . The ovesistance . Chen etion rate . p = 0.170) [H. pylori infection.The success rate of AST-guided second-line/rescue regimens is lower than that of first-line regimens. The eradication rate is poor (68%) despite susceptibility testing for salvage treatment . Likewis= 0.170) . TherefoH. pylori eradication in a prospective study in Spain (94.4% (ITT) and 96.2% (PP)) [H. pylori eradication rate, but patient compliance may be reduced because of the large number of drugs. In addition, BQT is administered four times daily, which may also reduce patient compliance. To overcome this, twice daily BQT regimens have been introduced, and studies in South Korea have demonstrated their effectiveness [H. pylori eradication and well-tolerated (86.5% (ITT) and 94.6% (PP)) [p < 0.001) [Bismuth quadruple therapy (BQT) consists of bismuth, a PPI, metronidazole, and tetracycline. It is recommended as the first-line regimen by the Toronto Consensus, Maastricht V/Florence Consensus, and the American College of Gastroenterology (ACG) guidelines ,9,10. Th2% (PP)) . BQT hastiveness ,45. Kim tiveness . A singl6% (PP)) . In an I6% (PP)) . In a me6% (PP)) . A 7-day< 0.001) . H. pylori eradication. Resistance to metronidazole can be overcome by increasing the frequency, amount, and duration of administration, so treatment for \u226510 days is recommended in areas with a high rate of metronidazole resistance [Whether the eradication rate improves when the treatment period is extended from 7 to 14 days is unclear. The Maastricht V/Florence Consensus recommends administration for at least 10 days ,51. Thersistance . BQT has been reported to have excellent results in various studies, and the scope of its application is gradually expanding. In addition, BQT can be used relatively safely in patients with penicillin allergy . BQT repp = 0.02 and 92% vs. 74% (PP), p = 0.05), and the eradication rate of concomitant therapy was superior to that of sequential therapy for antibiotic-resistant strains [H. pylori eradication rates in PP and ITT analyses [Concomitant therapy, three antibiotics and PPI administered concomitantly, is recommended for 10 to 14 days ,10. Seve strains . In addianalyses . Moreoveanalyses ,60. p = 0.15; 91% vs. 86% (PP), p = 0.131) [Concomitant therapy is preferred over sequential therapy because it is simpler. There is controversy over whether concomitant therapy is superior to sequential therapy ,63,64,65= 0.131) ,67. H. pylori strains. Conversely, when H. pylori is susceptible to clarithromycin and resistant to metronidazole, sequential therapy shows a lower eradication rate than STT [H. pylori. The eradication rate of sequential therapy is low because the period of metronidazole administration is only 5 days.The Maastricht V/Florence consensus does not recommend sequential therapy, unlike previous guidelines . This isthan STT . IncreasH. pylori treatment [H. pylori, resistant to both clarithromycin and metronidazole [Concomitant therapy has several limitations, such as a higher rate of adverse events than sequential therapy . An incrreatment ,70. Althreatment . Finallynidazole . Hybrid therapy is a combination of sequential and concomitant therapy. Hybrid therapy comprises a PPI and amoxicillin for 7 days, followed by a PPI, amoxicillin, clarithromycin, and metronidazole for 7 days . AlthougH. pylori infection in areas with high rates of clarithromycin and metronidazole resistance; this is similar to the eradication rate of concomitant therapy [p = 0.05). However, the eradication rate of hybrid therapy is significantly lower for dual-resistant H. pylori. In a prospective study, the eradication rate in patients with dual antibiotic resistance (clarithromycin and metronidazole) was noticeably decreased (50%) compared to those with only clarithromycin resistance (91.4%) or metronidazole (90.5%) resistance [In a prospective multicenter study, hybrid therapy cured >90% of patients with therapy . In addisistance . H. pylori infection [H. pylori eradication rate of 97.2% of levofloxacin-susceptible cases and 84.0% of levofloxacin-resistant cases [H. pylori [H. pylori infection [p < 0.05) [Levofloxacin is active on a large spectrum of various bacteria, and some studies use levofloxacin as the first-line treatment of nfection . A prospnt cases . Howevernt cases . Gan et . pylori . The era. pylori . There anfection . The eranfection . The LOAnfection . Basu et < 0.05) . H. pylori. Therefore, many patients have a history of exposure to levofloxacin. Most guidelines recommend that levofloxacin-based regimens be applied as a rescue rather than a first-line therapy [Levofloxacin is a quinolone and is widely used worldwide for, for instance, pneumonia, urinary tract infection, tuberculosis, and therapy . The ACG therapy . gyrA mutation-positive H. pylori strains [H. pylori eradication (75.8% (ITT) and 83.3% (PP)) [H. pylori [gyrA mutation-positive H. pylori should be evaluated.Sitafloxacin is a fourth-generation fluoroquinolone and has potent activity against strains . Sitaflo. pylori ,85. Amon. pylori . The effMycobacterium avium-intracellulare and M. tuberculosis resistant to rifampicin [Helicobacter DNA-dependent RNA polymerase, which is encoded by rpoB. Therefore, mutation of rpoB confers resistance to rifabutin [H. pylori eradication [H. pylori eradication failed following treatment with conventional antibiotics [H. pylori is low because it is rarely used clinically [Rifabutin is a rifamycin derivative and structurally similar to rifampicin (anti-tuberculosis drug). It is mainly used for atypical tuberculosis, such as fampicin . Rifabutifabutin . All extdication . Accordidication . In an Iibiotics . Rifabutibiotics ,90. In ainically ,91. Therinically . As therH. pylori [rpoB and increases the minimum inhibitory concentration (MIC) of rifabutin, previous rifampicin treatment must be determined before administering rifabutin [To date, most studies on rifabutin-based regimens have focused on rescue therapy. Recently Graham et al. showed that a rifabutin-based triple regimen had a higher eradication rate than amoxicillin plus a PPI as the first-line empirical treatment of < 0.001) . This su< 0.001) . Moreoveifabutin . Finallyifabutin . H. pylori, gastric pH must be maintained above a certain level to enable antibiotic activity [+ and K+-ATPase-mediated gastric acid secretion and is acid-stable and less impaired by the CYP2C19 system than PPIs [H. pylori regimen containing PCAB has attracted attention [H. pylori treatment.Potassium-competitive acid blocker (P-CAB) is an inhibitor of gastric acid secretion, with a faster onset and longer-acting acid suppression, and is more potent than a PPI ,97. In aactivity . P-CAB ihan PPIs ,99. Becattention . Vonoprap < 0.0001) [p < 0.0001) [H. pylori eradication (97.4% vs. 95.7%) [H. pylori treatment, the eradication rates of dual (vonoprazan and low-dose amoxicillin) and triple therapies were 84.5% and 89.2% (p = 0.203) by ITT analysis, respectively, and 87.1% and 90.2% (p = 0.372) by PP analysis, respectively [H. pylori. According to a multicenter RCT in Japan, the first-line eradication rate of vonoprazan-based triple therapy was 92.6% vs. 75.9% for STT ( 0.0001) . A meta- 0.0001) . By cont. 95.7%) . In a stectively . In the H. pylori eradication. Murakami et al. demonstrated the efficacy of a P-CAB-based second-line triple regimen (success rate of 98.0%) [H. pylori (83.3% vs. 57.1% (PP), p = 0.043) [H. pylori eradication.In Japan, P-CAB-based regimens are licensed as first- and second-line treatment for f 98.0%) . AnotherH. pylori [All guidelines recommend avoiding antibiotics taken by a patient previously ,8,9,10. . pylori . Suscept. pylori . According to the Maastricht V/Florence Consensus, after the failure of BQT as first-line treatment, a quinolone-containing triple or quadruple therapy is recommended . After tThe Toronto Consensus and the ACG guidelines, like the Maastricht V/Florence Consensus, emphasize the importance of BQT and levofloxacin-containing regimens as second-line ,9. An imH. pylori. H. pylori treatment is an important global issue because it has been directly implicated as a cause of several gastrointestinal diseases. There is clear concern about increased rates of resistance over time, highlighting the necessity for suitable antibiotic use going forward to minimize further growth of antibiotic resistance. AST-based tailored therapy showed a good eradication rate when applied first-line. Because the rate of antibiotic resistance of H. pylori is increasing, the role of tailored therapies should be expanded. However, if tailored therapy cannot be applied to all patients due to realistic problems, using a locally highly effective empiric regimen is a reasonable alternative. In addition, when using such an empiric regimen, a simple and efficient H. pylori treatment strategy is needed. Therefore, we suggest BQT as first-line therapy when AST or regional resistance data are not available if resistance to clarithromycin has not been studied. Further work should focus on maximizing the therapeutic effects of tailored therapies based on the results of AST.Tailored therapy, according to the AST results, promotes"} +{"text": "Tick-borne diseases are of substantial concern worldwide in both humans and animals. Several hard tick species are of medical and veterinary interest in Europe, and changes in the range of tick species can affect the spread of zoonotic pathogens. The aim of the present study was to map the current prevalence and distribution pattern of ticks and related tick-borne pathogens in Latvia, a Baltic state in northern Europe.Ixodes ricinus, I. persulcatus and Dermacentor reticulatus tick samples were collected in all regions of Latvia during 2017\u20132019 and were screened by molecular methods to reveal the prevalence and distribution pattern of a wide spectrum of tick-borne pathogens.Nearly 4600 D. reticulatus occurrence were found in western and central Latvia, including the Riga region, indicating that the northern border of D. reticulatus in Europe has moved farther to the north. Among the analyzed ticks, 33.42% carried at least one tick-borne pathogen, and 5.55% of tick samples were positive for two or three pathogens. A higher overall prevalence of tick-borne pathogens was observed in I. ricinus (34.92%) and I. persulcatus (31.65%) than in D. reticulatus (24.2%). The molecular analysis revealed the presence of tick-borne encephalitis virus, Babesia spp., Borrelia spp., Anaplasma phagocytophilum and Rickettsia spp. Overall, 15 and 7 tick-borne pathogen species were detected in Ixodes spp. and D. reticulatus ticks, respectively. This is the first report of Borrelia miyamotoi in Latvian field-collected ticks.New localities of Ixodes and Dermacentor ticks in Latvia and gives us a reliable overview of tick-borne pathogens in Latvian field-collected ticks.This large-scale countrywide study provides a snapshot of the current distribution patterns of Ixodes ricinus; I. persulcatus; and Dermacentor reticulatus and 2.5\u00a0\u03bcl of proteinase K (20 mg/ml) were added to 100 \u03bcl of a tick suspension, and the mixture was incubated at 50\u00a0\u00b0C for 1 h. DNA was extracted Babesia spp., Borrelia spp., A. phagocytophilum and Rickettsia spp. using a nested polymerase chain reaction (PCR) targeting the 18S rRNA, 16S rRNA and gltA genes, respectively, as previously described [All samples were tested for the presence of escribed . The preescribed .Borrelia burgdorferi (sensu stricto) B31 strain ; A. phagocytophilum Webster strain ; Rickettsia helvetica-positive tick sample Lv-P44, which we acquired in a previous study [Babesia canis-positive clinical sample Lv-dog 2 (positive DNA sample from dog blood), which we also detected in a previous study [To prevent PCR amplicon contamination, sample DNA/RNA preparation, reaction preparation, PCR amplification, and amplicon detection were all performed in separate areas using filter tips. Both negative and positive controls were included in all PCR amplification steps. As a negative control, PCR mixtures without DNA were used. As positive controls for PCR, the following specimens were used: us study ; and Babus study . All prihttp://www.ncbi.nlm.nih.gov/genbank) and BLAST software [http://www.ncbi.nlm.nih.gov/BLAST). Pathogen genotypes were assigned based on sequence similarity (99\u2013100%) with the corresponding genes of the reference strains.Positive PCR amplicons were purified and analyzed by Sanger sequencing from both DNA strands using the BigDye Terminator v3.1 Cycle Sequencing Kit in an ABI Prism 3100 Genetic Analyzer . Sequence chromatograms were viewed and edited using Finch TV Version 1.4.0 software . Primer sequences were omitted in all sample sequences. Pathogens were identified using the NCBI GenBank database . P-values were adjusted for multiple testing by Holm correction in R using the R statistical package [P \u2264 0.05 were considered significant.All ticks were processed individually, and their prevalence was expressed as a percentage. The prevalence of pathogens was calculated with the 95% confidence intervals of a proportion by the \u201cexact\u201d method of Clopper and Pearson . A package . Values I. ricinus , I. persulcatus , and D. reticulatus . Based on geolocation data, the distribution of these species in Latvia was mapped. As expected, I. ricinus was present across the whole country, and the distribution of I. persulcatus was restricted to the eastern and northern-eastern Vidzeme and Latgale regions and the differences were statistically significant ; Bo. garinii; Bo. lusitaniae; and Bo. valaisiana. In D. reticulatus ticks, 7 pathogens were detected: TBEV; Ba. canis; R. helvetica; R. raoultii; Bo. afzelii; Bo. garinii; and A. phagocytophilum.The molecular analysis indicated the presence of 15 tick-borne pathogens in Rickettsia spp. were detected in the tick samples most frequently: 19.46% (894/4593) of the ticks were Rickettsia-positive. Ixodes persulcatus ticks were Rickettsia-positive significantly less frequently (7.59%) than I. ricinus (19.45%) and D. reticulatus (22.69%) than that in either I. persulcatus (6.33%) or D. reticulatus (5.21%) ticks . On the other hand, R. raoultii was associated mainly with D. reticulatus, in which this pathogen was detected in 17.82% of samples, in comparison with 2.11% of I. ricinus and 1.27% of I. persulcatus ticks . Rickettsia monacensis was detected only in 5 I. ricinus samples (0.13%) (Table\u00a0iculatus 2.69% (ORBabesia pathogens was significantly higher in I. ricinus ticks than in I. persulcatus and D. reticulatus (2.53% vs 0.63% and 0.34%) . Babesia microti and Ba. canis were the only Babesia species detected in I. persulcatus and D. reticulatus, respectively. Surprisingly, very similar proportions of field-collected I. ricinus and D. reticulatus ticks were Ba. canis-positive in this study (0.91% vs 0.34%) . However, Ba. canis-positive samples were found only in areas with the sympatric occurrence of I. ricinus and D. reticulatus and A. phagocytophilum, were all detected in tick samples in our study. Importantly, TBEV was detected in nearly identical proportions of I. ricinus, I. persulcatus and D. reticulatus samples Table\u00a0. The geoA. phagocytophilum, was found in 1.2, 0.63 and 0.5% of I. ricinus, I. persulcatus and D. reticulatus ticks, respectively; the differences were not statistically significant. This pathogen was detected mainly in ticks in the western, central and northern regions of Latvia group spirochaetes were detected in 15.99% and 23.42% of I. ricinus and I. persulcatus ticks, respectively, while only 1.01% (6/595) of D. reticulatus were Borrelia-positive in this study; this difference was statistically significant (Table\u00a0I. persulcatus ticks were Bo. burgdorferi (s.l.) positive significantly more frequently than I. ricinus . Within this pathogen group, the genotyping analysis revealed the presence of Bo. afzelii, Bo. burgdorferi (s.s.), Bo. garinii, Bo. lusitaniae and Bo. valaisiana. The most abundant species was Bo. afzelii, which was detected in 9.35 and 15.19% of I. ricinus and I. persulcatus ticks, respectively. Borrelia afzelii was also the only Lyme disease-causing spirochaete present in several D. reticulatus ticks were detected in 2.5%, 1.22% and 0.6% of I. ricinus ticks.The geolocation data showed that Lyme disease-causing pathogens were present in host-seeking ticks throughout the territory of Latvia Fig.\u00a0a. BorrelBo. miyamotoi was present solely in Ixodes ticks ; no Bo. miyamotoi-positive D. reticulatus samples were found in this study group, was detected in 6.3%, 3.16% and 1.34% of the I. ricinus, I. persulcatus and D. reticulatus samples, respectively, and the difference between I. ricinus and D. reticulatus was statistically significant (Table\u00a0Bo. burgdorferi (s.l.) and Rickettsia spp. (2.94%). Importantly, co-infection of Bo. burgdorferi (s.l.) with TBEV was found in 0.1% and 0.63% of I. ricinus and I. persulcatus ticks, and co-infection with three pathogens was detected in 0.55% (21/3840) of I. ricinus ticks in our study of the host-seeking tick samples were positive for more than one tick-borne infectious agent. Co-infection with two or three tick-borne pathogens, including two genotypes of the 55/4593 oI. ricinus, I. persulcatus and D. reticulatus, and the prevalence of tick-associated pathogens in Latvia was investigated. This is the most comprehensive countrywide study including host-seeking tick samples collected during 2017\u20132019.Here, the distribution of three tick species, I. persulcatus was in accord with previous observations, as this tick species was found in northern and eastern parts of the country. The geolocation data of the tick collection sites revealed new localities of D. reticulatus occurrence in western and central Latvia, in addition to the previously observed locations [D. reticulatus has efficiently expanded its range in Latvia, and the northern border of D. reticulatus in Europe has moved farther north. Moreover, D. reticulatus has been detected in geographically separate new localities in the Riga region, indicating the development of new foci outside of the major distribution area. Similar to these findings, we reported in a recent study that from 2011 to 2016, D. reticulatus ticks were removed from dogs in western, southern and central parts of Latvia and the Riga region [D. reticulatus during the last decade has been notable in other European countries such as neighboring Lithuania [As expected, all three epidemiologically important tick species were present in Latvia. The distribution of ocations . Thus, ta region . Outsideithuania , 11, 19.ithuania , 20.Ixodes ticks and only a few pathogens and/or geographical locations, and the most recent studies on the prevalence of the highly medically important Borrelia spp. and TBEV in host-seeking ticks were published in 2004 and 2013, respectively [Borrelia, Babesia, Anaplasma and Rickettsia pathogens was studied in all three medically important tick species.Increases in human travel, animal transport, and environmental changes, including the establishment of new tick foci, are responsible for the emergence and/or spread of numerous tick-borne pathogens . In Euroectively \u201329. TherRickettsia spp. were detected in nearly 20% of all ticks. Three Rickettsia species were identified: R. helvetica, R. monacensis and R. raoultii. Rickettsia helvetica has been detected in Ixodes ticks in many European and Asian countries, and there is evidence that it may cause disease in humans [R. monacensis infection in humans have been reported in Spain, Italy, the Netherlands and South Korea [R. helvetica and R. monacensis were mainly associated with I. ricinus ticks, and infection rates were similar to those reported earlier in eastern European countries [R. helvetica was found in D. reticulatus ticks in our study (5.21%), and 17.82% of the specimens of this tick species were R. raoultii-positive. Rickettsia raoultii is frequently detected in multiple tick species and, along with R. slovaca, is a causative agent of a syndrome in humans known as DEBONEL/TIBOLA (Dermacentor-borne necrosis erythema and lymphadenopathy/tick-borne lymphadenopathy), a newly recognized emerging disease [I. ricinus and I. persulcatus ticks were R. raoultii-positive in this study, and some of these samples were collected in Latvian regions where D. reticulatus ticks are absent. These findings indicate the involvement of other factors, such as the availability of suitable reservoir animals, in the spread of this emerging pathogen.Tick-borne rickettsiae are considered to be emerging; thus, it is important to obtain comprehensive data on the occurrence and prevalence of spotted fever group rickettsiae across Europe. In this study, n humans . On the th Korea . In our ountries . Additio disease , 34. ThuA. phagocytophilum is of both public health and veterinary importance. This pathogen is a generalist, has a very broad range of hosts and causes disease in many mammalian species, including humans [A. phagocytophilum in Europe is I. ricinus, but this pathogen has also been found in other tick species, including D. reticulatus [A. phagocytophilum is found in all European countries [A. phagocytophilum was identified at similar proportions in all three tick species, and its overall prevalence was 1.09%. This finding confirmed the risk to humans and animals.The tick-borne pathogen g humans . Human gg humans . The maiiculatus , 38. Theountries . In our Ixodes ticks, Bo. miyamotoi, a member of the relapsing fever group spirochaetes, as well as the Lyme-disease spirochaetes Bo. burgdorferi (s.s.), Bo. afzelii, Bo. garinii, Bo. valaisiana and Bo. lusitaniae were recorded, among which Bo. afzelii was the predominant species . The total prevalence of Bo. burgdorferi (s.l.) spirochaetes in I. persulcatus ticks was significantly higher than that in I. ricinus (23.42 vs 15.99%); this result is in accordance with previous studies conducted in regions of sympatric tick occurrence [Bo. burgdorferi (s.l.) in I. ricinus was 18.6% [Bo. miyamotoi in field-collected ticks in Latvia. This pathogen was found in both I. ricinus and I. persulcatus ticks, and the prevalence rates were in accordance with the results of studies conducted in the neighboring countries of Estonia, Sweden and Finland [D. reticulatus ticks, six (1.01%) were positive for Bo. burgdorferi (s.l.); both Bo. afzelii and Bo. garinii were detected. The presence of Lyme disease pathogens in D. reticulatus ticks has been previously reported in European countries [In Latvian currence , 40. Addas 18.6% . This is Finland , 42, 43.ountries ; thus, iD. reticulatus for TBEV is still unclear. A recent study reported the repeated isolation of TBEV from adult D. reticulatus ticks in Germany, and it was suggested that D. reticulatus plays an equal role to I. ricinus in TBEV circulation when the two tick species are sympatric [D. reticulatus tick, corresponding to an overall prevalence of 0.67% (4/595). Similar proportions of I. ricinus and I. persulcatus ticks were TBEV-positive. Previously, it was shown that from 1993 to 2002, the annual TBEV infection rate of field-collected adult ticks among I. ricinus adults varied between 1.7% and 26.6%, while for I. persulcatus, it varied between 0% and 37.3% [Ixodes species was not statistically significant (1.02% for I. persulcatus and 1.51% for I. ricinus) [Similar to the situation for Lyme disease pathogens, the vector competence of ympatric . In our nd 37.3% . Anotherricinus) . In the ricinus) . This fiBabesia, Ba. microti, Ba. venatorum, Ba. capreoli and Ba. canis were detected in this study. Both Ba. microti and Ba. venatorum are considered to pose a zoonotic risk to humans [I. ricinus ticks (0.55%) carried Ba. microti, and 41 (1.07%) carried Ba. venatorum. Additionally, a single I. persulcatus tick was Ba. microti-positive in this study (0.63%). Overall, these findings are similar to the results of our previous study in Ixodes ticks collected during 2005\u20132007, except that both Ba. microti and Ba. venatorum were detected in I. persulcatus ticks in the previous study [Babesia species were present in different regions of Latvia. On the other hand, 0.91% of I. ricinus ticks (35/3840) carried Ba. canis, the agent of canine babesiosis, which is usually strongly associated with D. reticulatus ticks. The presence of Ba. canis in I. ricinus observed here is in accordance with a study conducted by Cieniuch et al. [I. ricinus ticks were infected, and also agrees with our recent study on ticks collected from dogs [Ba. canis in field-collected D. reticulatus was very low, as only two samples out of 595 (0.34%) were positive for this species. In contrast, 14.8% of D. reticulatus ticks removed from Latvian dogs were Ba. canis-positive [Babesia in D. reticulatus ticks from southern Latvia was 2.8%; however, the prevalence of different species was not studied. Based on the molecular screening of field-collected ticks, the prevalence of Ba. canis in adult D. reticulatus ticks in Europe varies from 0% to 14.8% (see [Ba. canis was present in 0.9% of D. reticulatus ticks in north-western Europe [Ba. canis-positive samples (disregarding the tick species) revealed the presence of several compact, geographically separated foci, suggesting an uneven, mosaic-like distribution in nature. Similarly, in a recent study in England, most of D. reticulatus ticks at a collection site related to an outbreak of canine babesiosis were Ba. canis-positive, while in other locations, all but one of the ticks were Ba. canis negative [Within o humans . In totaus study . The geoh et al. in Polanrom dogs . Interespositive . In a stpositive , the ove study 0.3%. Overan Europe . Additionegative . The exiI. ricinus (6.3%) than in D. reticulatus (1.34%) ticks; 3.16% of I. persulcatus ticks were also positive for more than one pathogen. High variability of co-infections was observed. The coexistence of multiple pathogens in Ixodes ticks has been reported in the USA, Europe and Asia, and most co-infections involve two of the three major human pathogens, i.e. Bo. burgdorferi (s.l.), A. phagocytophilum and Babesia spp. (see [Ixodes ticks [Bo. burgdorferi (s.l.) with Rickettsia was observed most frequently; however, the total number of different pathogen combinations was as high as 57. Thus, awareness regarding possible co-infections in ticks should be increased, and further studies are needed, especially in the background of climate change and the emergence and spread of sympatric areas for Ixodes and Dermacentor tick species.Importantly, the presence of two or three pathogens was found in a considerable portion of host-seeking ticks in our study. The total co-infection rate was 5.55%; however, co-infections were found significantly more often in pp. ."} +{"text": "Scientific Reports 10.1038/s41598-020-74676-8, published online 19 October 2020Correction to: The original version of this Article contained errors in the spelling of the author Domagoj Cikes which was incorrectly given as Cikes Domagoj.The Author Contribution section now reads:C.S.O. and V.R. designed research; C.S.O. and L.M. performed cell culture experiments; D.C., E.K. and J.M.P. performed Biomechanical experiments; E.W., J.C.G. and V.R. generated muscle cell bundle; C.S.O. and B.M.K. generated the shPab proteome; I.L. and Y.C. generated the aging transcriptome; C.S.O. and V.R. wrote the paper; All authors commented on the manuscript.These errors have now been corrected in the PDF and HTML versions of the Article and the Supplementary Information file that accompanies the Article."} +{"text": "Scientific Reports 10.1038/s41598-020-70492-2, Published: 12 August 2020Correction to: The original version of this Article contained errors in the spelling of the authors\u00a0Marcelo B. Sztein and Andrea C. Bafford which were incorrectly given as M. B. Sztein and A. C. Bafford respectively.Furthermore, in the Author Contributions section the initials of the authors R.S.-G., A.C.B. and M.B.S. were incorrectly given as R.S., A.B. and M.S.Finally, the Supplementary Information file contained errors in the spelling of the authors\u00a0Marcelo B. Sztein, Andrea C. Bafford and Ros\u00e2ngela Salerno-Goncalves which were incorrectly given as M. B. Sztein, A. C. Bafford and R. Salerno\u2010Goncalves respectively.These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Scientific Reports 10.1038/s41598-020-58282-2, published online 27 January 2020Correction to: The original version of this Article contained errors.The spelling of the author \u2018Knut Rudi\u2019 was incorrectly given as \u2018Rudi Knut\u2019.As a result, in the Author Contributions,\u201cC.-A.R., S.B.-G., A.-\u0218.A., E.S., A.B., I.L., R.K. and C.C. carried out the experimental work.\u201dnow reads:\u201cC.-A.R., S.B.-G., A.-\u0218.A., E.S., A.B., I.L., K.R. and C.C. carried out the experimental work.\u201dIn addition, there was an error in Affiliation 6, which was incorrectly given as \u2018Norwegian University of Life Sciences, 3 Universitet Student, 1430, Aas, Norway.\u2019 The correct affiliation is listed below:\u2018Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, \u00c5s, Norway.\u2019These errors have now been corrected in the HTML and PDF versions of the Article."} +{"text": "Correction to: Scientific Reports 10.1038/s41598-019-44967-w, published 28 June 2019.In the original version of this Article, A. Kiani was incorrectly listed as the corresponding author. The correct corresponding author for this Article is F. Geran. Correspondence and request for materials should be addressed to f.geran@sru.ac.ir.This error has now been corrected in the HTML and PDF versions of the Article."} +{"text": "Morus alba is an essential species that is mainly considered to be economically important due to their potential use as silk production, medicine and food. In this work, we evaluated the data of effects of different concentration of Waste Tea Residue Carbon Dots (WTR-CDs) on the ex\u00a0vitro growth of morus. This dataset can be beneficial for researchers finding alternative eco-friendly, biodegradable and cost-friendly substitute for plant growth stimulator that are helpful for plant propagation during plant production program. Time consuming and low germination ratio of seeds are the most restricting triggers for commercial use for large-scale cultivation of plant species. Use of WTR-CDs in ex\u00a0vitro culture technology is an appropriate alternative approach for large-scale production of plants within a short period of time.The data article In M. alba.Dataset in figures , Fig.\u00a05 22.1M. alba) were taken from a single mother plant in the Shivaji University, Kolhapur (Maharashtra) campus. Around 60 healthy nodal explants cutting in the form of pencil size diameter and 5\u20136 cm length for plant propagation. Those nodal explants were cut near about 45\u00b0 angel from the base side of plant stick stem with one bud, Instead, 0.1% (w/v) mercury chloride was used for surface sterilized for 30 min after that treatment rinsing them with sterile distilled water for five times.Mulberry plants in six set, set II, III, IV, V and VI was dipped in 20 mL of 50, 100, 150, 200 and 250 mg/L WTR-CDs solutions respectively for 7 days in beaker where five cuttings of nodal explant were exposed to two treatments (control and optimized concentration of WTR-CDs) and five times replicate. After bud formation, some bud formed 2.5t-Test: Paired Two Sample for Means.The dataset collected was examined using Analysis of Variance (Single factor ANOVA) and the means were using Conceptualization, R.D.W., A.H.G. and G.B.K.; Methodology, R.D.W. and A.H.G.; Data curation, R.D.W.; Writing-original draft preparation, R.D.W. and A.H.G; Writing-review & editing, P.V.A., D.S., and G.B.K.; Visualization, R.D.W. and A.H.G.; Supervision, P.V.A. and G.B.K."} +{"text": "Scientific Reports 10.1038/srep39015, published online 16 December 2016Correction to: An institutional investigation at the JAXA Human Spaceflight Technology Directorate concluded that Ikuya Nonaka and Shin Yamada did not make contributions to writing the paper, analysing the data, or checking and confirming the contents of the paper. Ikuya Nonaka and Shin Yamada should not be listed as authors of the Article. The author list should read:\u201cHiroko P. Indo, Hideyuki J. Majima, Masahiro Terada, Shigeaki Suenaga, Kazuo Tomita, Akira Higashibata, Noriaki Ishioka, Takuro Kanekura, Clare L. Hawkins, Michael J. Davies, Daret K. St Clair & Chiaki Mukai\u201dThe Author Contribution statement should read:\u201cH.P.I., S.S., K.T. and T.K. contributed to the whole analyses and discussion of the results. M.T., C.L.H., M.D., D.K.S. and H.J.M. contributed to the experimental planning and discussion of the results. A.H., N.I., C.M., contributed to all of these aspects in this study, including drafting the manuscript and executing the final revisions. All authors approved the final manuscript prior to publication.\u201dThe Acknowledgements should read:\u201cThis study was supported in part by the JAXA-ISS Space Medicine Program Grant from the Japan Aerospace Exploration Agency. The authors gratefully thank the astronaut who took part in this study, Dr. Satoshi Furukawa and Dr. Shin Yamada of JAXA for their encouragement to complete this study, Dr. Ikuya Nonaka, National Center Hospital for Mental Nervous and Muscular Disorders, who contributed to start up this project, Professor John Tremarco of Kagoshima University for his help and guidance during the preparation of this manuscript.\u201d"} +{"text": "The article is about the role of transposons in the regulation of functioning of neuronal stem cellsand mature neurons of the human brain. Starting from the first division of the zygote, embryonic developmentis governed by regular activations of transposable elements, which are necessary for the sequential regulationof the expression of genes specific for each cell type. These processes include differentiation of neuronal stemcells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, inthe hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, whichcauses somatic mosaicismof cells during the formation of specific brain structures. Similar data were obtained instudies on experimental animals. Mobile genetic elements are the most important sources of long non-codingRNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-codingRNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function.MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating thedifferentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take anactive part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposonsin the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplicationand domestication. These genes are involved in an epigenetic regulatory network with the participationof transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNAformed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help ofthe Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism forthe implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into thegenome with a regulatory effect on the genes involved in the memory. Transposable elements (TE) make up 69 % of the human genome. In the course of evolution, manyprotein-coding genes , regulatorynucleotide sequences , and telomeres , non-coding RNAs(ncRNAs), including microRNAs and long humanncRNAs originating from TE. Overmillions of years of evolution, cells have developed variousdefense systems against TE insertion into their genomes,including DNA methylation, heterochromatin formation,and RNA interference (RNAi). These epigenetic mechanismshave made a significant contribution to the regulation of specificgene expression and cell differentiation .Transposable elements are divided into two main classes,in accordance with the mechanisms of their transposition.DNA-TEs are transposed by \u201ccut and paste\u201d or \u201crolling circle\u201d.Retroelements (REs) are integrated into new genome sitesusing \u201ccopy and paste\u201d. REs are classified into those containinglong terminal repeats (LTR REs) and those notcontaining them (non-LTR REs) . The latter are dividedinto autonomous and non-autonomous and SVA (SINE-VNTR-Alu) .The human genome contains more than 500,000 copies ofLINE1 (L1), which make up 17 % of all nucleotide sequences.Among them, only about 100 L1 are active, since they containthe full length of 6000 bp. Among non-autonomous REs,the human genome contains more than 2700 copies of SVA. One of the important factors forthe development of the human brain is considered the wavesof L1 retrotranspositions, as well as the birth of new TEs, suchas SINE, Alu and SVA in the evolution of primates .Human endogenous retroviruses (HERV) belong to LTRRE.They occupy about 8 % of the entire genome and serveas sources of a huge number of binding sites withspecific transcription factors (TFs), the activation of whichplays a role in embryogenesis. For example, in the mesoderm,LTRs interact with SOX17, FOXA1, GATA4; in pluripotentcells, with SOX2, NANOG, POU5F1; in hematopoietic cells,with TAL1, GATA1, PU1 . Mammalian-wideinterspersed repeats (MIRs), which belong to the ancient SINEfamily descended from tRNA, are also associated with tissuespecificgene expression .Transposable elements are characterized by nonrandomactivation, depending on the tissue and stage of development. High-throughput profiling of integration sites by nextgenerationsequencing, combined with large-scale genomicdata mining and cellular or biochemical approaches, hasrevealed that the insertions are usually non-random . Programmed activation of TE in individual cellsduring neurogenesis leads to a change in the expression ofcertain genes necessary for differentiation into specific types ofneurons for the formation and functioning of brain structures. In accordance with this,somatic mosaicism of neurons detected by insertions of TEs can reflect the programmed regulatory pattern of thegenome necessary for the maturation of specific structures ofthe central nervous system . Somatic mosaicism means the presence, in the sameorganism, of cells with different genomes as a result of de novoDNA changes. These structural variations may be due to CNV,insertions of REs, deletions under the influence of TEs, andSNV . This means that in different cellsof one organism, not only the genotype, but also the wholegenome changes. This is due to the occurrence of mutations inexons of protein-coding genes, intergenic regulatory regionsand introns, which is accompanied by a specific expressionof certain genes specific for each cell type.The human brain contains an average of 86.1 billion neurons.Moreover, each of the neurons forms from 5,000 to 20,000synaptic connections, creating a complex network with avariety of cell types and subtypes. The number of subtypesof neurons is so large that it does not lend itself to modernmethods for their description. There must be mechanisms toensure such a diversity of neurons with their specific temporaland spatial features of functioning .The sources of these mechanisms can be TEs, combinations ofmovements of which can become sources of countless variety.An example of this is the molecular mechanism for generatingantibodies by the mammalian immune system (V(D)Jrecombination), derived from TEs . TEsplayed a role in the development of the central nervous system.In evolution, they turned out to be sources of the formationof regulatory structures and genes involved in the formationof the brain. Non-autonomous TEs MER130 were preservedin the genomes during evolution due to their location nearthe neocortex genes as a necessary link for their regulation.The experiments showed the activation of MER130 in mouse embryos on the fourteenth day of development as gene enhancersfor the development of the neocortex . Among 11 sushi-ichi-specific placental animal genesderived from REs, the SIRH11/ZCCHC16 gene encodingzinc finger CCHC protein contributed to the evolution of thebrain. This domesticated gene is involved in the developmentof cognitive functions of placental animals .In 2009, in neuronal stem cells isolated from the brain ofa human embryo, L1s retrotranspositions were detected, aswell as an increase in the number of copies of endogenousL1s in the adult hippocampus . In additionto L1 (7743 insertions), a large number of somatic transpositionsAlu and SVA (1350 insertions) werefound in the hippocampus of adults . Thesede novo integrations can affect the expression of certain genes,creating unique transcriptomes of individual neurons . This may be due to the genome-programmed TE abilityfor their regular site-specific insertions .In 2009, of 19 retrotranspositions, 16 were found at a distanceof less than 100 kilobases from genes expressed in neurons. In 2015, in a study of the somatic mosaicismof the human hippocampus K.R. Upton et al. revealed,out of 20 identified L1 transpositions, 2 functionally significantinsertions into the introns of the ZFAND3 and USP33 genesfunctioning in the brain . A.A. Kurnosovet al., when studying human brain samples, showed that outof 3100 transpositions of L1 in neurons of the dentate gyrusof the hippocampus, 50.26 % of insertions are located in thegenes, and out of 2984 Alu, 49.1 % .In 2016, J.A. Erwin et al. revealed that in the brain of healthypeople 44\u201363 % of neurons undergo somatic mosaicism atthe loci of genes that are important for the functioning of thenervous system. For example, a high insertion frequency ofL1-RE is shown for the DLG2 gene, which affects cognitiveflexibility, attention, and learning. Mutations in DLG2 areassociated with the development of schizophrenia .Somatic retrotranspositions, unlike germinal ones, cannotbe inherited by future generations. However, the programmedability for specific insertions, depending on the compositionand location of TEs in the genome, can be inherited. An explanationof the ability of TEs to be inserted in a site-specificmanner in the region of genes expressed in the brain may bethe evolutionary relationship of protein-coding genes and theirregulatory sequences with TEs . The insertionsspecific for humans and chimpanzees were revealed nearthe promoters of the tachycin receptor genes TACR3, cationchannels TRPV1 and TRPV3, oxytocin OXT. These genes areassociated with the functioning of neuropeptides. Analysisof the genomes of various mammals showed that the neuralenhancer nPE2, which regulates the expression of the POMCgene in the hypothalamus, evolved from SINE in evolution.Transpositions and expression of TEs can vary dependingon the area of the brain and change under environmental influences,as they can perform a number of adaptive functions. More active are L1, which retainedthe ability to transpose, causing somatic mosaicism . In 2005, A.R. Muotri et al. suggested that L1using somatic transpositions can actively create mosaicism ofneuron genomes . In the brain, somaticmosaicism plays an important role in the regulation of cognitionand behavior. The consequences of somatic mosaicismencompass vast changes \u2013 from a variant at a single locus, togenes in neuronal networks . Moreover, the features of somatic mosaicismdiffer between neurons of various regions of the brain. Forexample, in the cerebral cortex, only 0.6 insertions of L1-REare observed, while in the hippocampus, from 80 to 800 insertsper neuron . Somatic mosaicism due toretrotranspositions is a source of phenotypic diversity betweenneurons during development. In the brain of an adult underthe influence of various environmental factors, L1 expressioncan affect the functioning of neurons during the formation oflong-term memory .The hippocampus is the center of human neurogenesis,where many insertions affect transcriptional expression, creatingunique transcriptomes in neurons. In addition, transcriptionalactivation of L1 is similar to that for the NeuroD1 gene.This may indicate the effect of L1 expression on neurogenesis,since stimulation of Wnt3a in neuronal stem cells increases L1expression 10-fold along the beta-catenin pathway, similarlyactivating transcription of the NeuroD1 gene. This gene encodesthe transcription factor that activates the genes involvedin neurogenesis. The NeuroD1 promoter region contains aSox/LEF site similar to the 5\u02b9UTR of the L1 element, andthe pattern of time expression of the NeuroD1 and L1 genesduring differentiation of neurons is similar .Genetic variations between neurons due to L1 retrotranspositionsmay be associated with specific enrichment of neuronalstem cell enhancers. It was shown that specific enhancersfor certain types of neurons (determined using FANTOM5)correspond to the coordinates in the genome for insertionsL1, which are within 100 bp from the enhancer. These patternshave not been identified for astrocytes and hepatocytes . When studying the features of L1 retrotranspositionsin more than 30 regions of the brain, a lot ofL1 insertion-specific cell lines were found . In experiments on mice, specific L1 expression wasalso shown depending on the area of the brain and the age ofthe animal .In addition to L1 elements, LTR-REs are also involved in theregulation of neurogenesis. For example, in mice, the regionwhere the full-length ERVmch8 on chromosome 8 was locatedwas comparatively less methylated in the cerebellum, due toits specific expression depending on the stage of development. In accordance with these data, it can be assumedthat the features of TEs activation observed in neuronalstem cells can naturally alter the expression of specific genesnecessary for differentiation of neurons during the formationof specific brain structures. The reason for the activation ofTEs in the neuronal stem cells of the hippocampus and thereason for their importance in memory consolidation may bethe sensitivity of TEs to stressful environmental influences. These mechanisms are aparticular reflection of the general pattern of epigenetic controlof the development of the whole organism, starting from thefirst division of the zygote, under the regulatory influenceof TEs . To understand therole of TEs in these processes, it is necessary to consider theirparticipation in embryogenesis.To initiate the development of the body after fertilization,gametes are reprogrammed to totipotency. During this reprogramming,TEs activation is observed. Previously, thisphenomenon was believed to be a side effect of extensivechromatin remodeling at the basis of epigenetic reprogrammingof gametes. However, a targeted epigenomic approachhas been performed to determine whether TEs directly affectchromatin organization and body development. It was foundthat silencing of L1 elements reduces the availability of chromatin,and prolonged activation of L1 prevents its gradualcompaction, which occurs naturally during development.That is, L1 activation is an integral part of the developmentprogram . In experiments on mice,the role of LTR-REs as a necessary control element for earlyembryogenesis was proved . For the cis-regulatory activity of the LTR retroelementsERVK, MERVL and GLN, a complex of RNA and proteinsis required, formed using the long ncRNA LincGET. Artificialsilencing of LincGET expression in the embryo at the bicellularstage leads to a complete halt to further developmentdue to disruption of cis-regulation of the genes necessaryfor proliferation under the influence of LTR-REs driven by LincGET. It has also been shown thatHERVs are activated in all types of human cells with characteristicfeatures for certain tissues and organs . In the study of the association of 112 TE families in24 human tissues, tissue-specific enrichment of active regionsof LTR-REs was noted, which indicates the involvement ofLTE-REs in the regulation of gene expression for differentiationof cells depending on their functional purpose in ontogenesis.This is due to the presence, in the TEs sequences, of transcription factors binding sites (TFBSs) that regulatethe development of the corresponding tissue. TE enrichmentcharacteristic of certain cells in intron enhancers correlateswith tissue-specific variations in the expression of nearbygenes .The genetic program in the 2-cell stage of embryogenesisin mice and humans is largely controlled by transcription factorsof the DUX family, which are key inducers of zygote genomeactivation in placental mammals .L1 transcripts in embryos are necessary for Dux silencing,rRNA synthesis and exit from the 2-cell stage. M. Perchardeet al. in their article showed that L1 expression is requiredfor preimplantation development .In embryonic cells, L1 transcripts act as a nuclear RNA scaffoldthat recruits Nucleolin and Kap1/Trim28 factors for Duxrepression. In parallel, L1 products mediate the binding ofNucleolin and Kap1 to rDNA, contributing to the synthesisof rRNA and self-renewal of embryonic stem cells . The role of L1 in the repression of the transcriptionalprogram of a 2-cell embryo indicates their participationin the development-specific regulation of gene expressionnecessary for cell differentiation and body development. It can be assumed that the activityof REs in neuronal stem cells indicates their use as switchesof transcription programs in the specific functionalizationof neurons. That is, TEs are involved in the management ofboth the differentiation of embryonic cells and postnatal stemcells. Regulation is carried out by implementing informationencoded in the features of the composition and distributionof TEs in the genome, through the sequential activation ofstrictly defined TEs in each new cell, specific for the tissueand stage of development. The greatest role is played by thisspecies-specific \u201ccoding\u201d in the brain, where neurons aredistinguished by higher activity of REs. This is reflected inthe structural and functional complexity of the brain comparedto other organs. The use of TEs as sources of ncRNAs playsan important role in these processes.According to recent data, from 75 to 85 % of the human genomeis transcribed into primary transcripts, while only 1.2 %of the genome is translated into proteins. Most transcripts areregistered as ncRNAs that are involved in the regulation ofthe genome . In humans, 13,000 genesof long ncRNAs have been identified, for the occurrence ofwhich HERVs are responsible by insertion of promoters.HERV-stimulated long ncRNAs are characterized by specifictranscription in different types of pluripotent cells, which isconsistent with the over-expression of these HERVs in humanembryonic stem cells . Transcriptionof most long ncRNAs is associated with the expression ofprotein coding genes according to the type of neurons and aspecific region of the brain. For example, according to AllenBrain Atlas in situ hybridization data, out of 1328 knownlong mouse ncRNAs, 849 are expressed in their brain andare associated with cell types and subcellular structures. Thebiological significance of these ncRNAs in the functioning ofneurons and their relationship with protein-coding genes hasbeen shown .Long ncRNAs expressed in the brain, such as Miat,Rmst, Gm17566, Gm14207, Gm16758, 2610307P16Rik,C230034O21Rik, 9930014A18Rik, share a similar expressionmodel with neurogenesis genes and overlap these genes, whichproves the role of long ncRNAs in neurogenesis . These data are consistent with the role of TEs in neurogenesis and regulation of brain function .This is because TEs are the main sources of the emergence andevolution of long ncRNAs, forming their functional domainsand making up more than 2/3 of their mature transcripts inhumans . REs can serve as genesfor long ncRNAs . L1s have a function similarto lncRNA in regulating the expression of genes necessary forself-renewal of stem cells and for preimplantation development.In a number of studies, the role of miRNAs in controllingthe differentiation of neurons, switching expression profiles ofgenes important for cell function in time and space has beenproved . About 40 % of all known humanmiRNAs are expressed in the human brain. The specificexpression of many of them differs in different types of cellsand is important in the regulation of differentiation, which isnecessary for a huge variety of phenotypes of neurons in thebrain . The accumulation of certainmiRNAs in various structures of neurons was revealed. For example, in experiments in mice,the role of miR-134 in the regulation of specific mRNAs of theLIMK1 gene for the growth of dendritic spins was shown, andthe accumulation of miR-99a, 124a1-3, 125b1, 125b2, 134,339 was noted in synaptosomes . The formationof neurites is promoted by miR-21 (the target is themRNA of the SPRY2 gene), miR-431 is involved in the regenerationof axons (the target is the Kremen-1 gene), differentiationof neurons occurs under the influence of miR- 34a andmiR-137 . Enhanced expressionof miR-9 promotes branching and reduced axongrowth by repressing microtubule-associated Map1b protein.Axon growth depends on the effect of miR-431, as well asmiR-17-92, which interacts with PTEN (phosphate tensinhomolog) in neurons of the cerebral cortex of the embryo.The regulatory role of differential expression of miR-221 andmiR-222 in neurogenesis has also been proven .In 2007, J. Piriyapongsa et al. found that in humans TEscan be sources of microRNAs ,which was confirmed by other researchers . The key role of TEs in the formationof microRNAsand long ncRNAs indicates that the maximum activityof TEs at the center of human neurogenesis as a natural phenomenon is necessary for epigeneticcontrol of differentiation of neuronal stem cells. Anothermechanism of TE participation in the regulation of gene expressionnecessary for the specific work of neurons is the cisandtrans-effects of TEs . This confirmsthe nonrandom activations of TEs as sources of heterogeneoussubpopulations of neurons .For the development and functioning of the brain, intercellularinteractions are necessary, the study of the regulationmechanisms of which is promising for therapeutic targetedexposure to the work of the brain. For this, it is important toidentify drivers for gene expression and post-transcriptionalepigenetic regulation of the structural components of neurons.Based on the analysis of the accumulated data on the role ofTEs in controlling the functioning of the genome in embryonicdevelopment and the physiological functioning of the humanbrain , it was concluded thatTEs are regulators of epigenetic control for gene function inontogenesis . Despitethe lack of mitotic activity of mature neurons, the specificexpression of TEs in them is important in controlling bothinterneuronal interactions and the structural and functionalcharacteristics of neurons . These properties may be dueto processing from transcripts of transposons of specific longncRNAs andmicroRNAs. Indeed, in experiments on laboratory animals,the enrichment of specific miRNAs in certain structures andregions of neurons was revealed. For example, an abundanceof miR-15b, miR-16, miR-204, miR-221 was found in thedistal axons compared to neuron bodies . Enrichment of specific miRNAs in synapses wasdetected. This suggests a local post-transcriptional regulationof the expression of neuron-specific genes .The role of miRNAs in intercellular interactions in the brainwas shown, as well as the value of the electrical activity ofneurons for the secretion of miR-124 and miR-9, which canpenetrate microglia and change the phenotype of its cells.Transposable elements regulate brain function throughexpression into specific microRNAs that regulate gene expressionin neurons and in intercellular interactions in the brain.The role of ERV in transferring information between neuronsfor memory consolidation has also been identified. In thehuman genome, the full-length HERV-K consists of the remains of ancient retroviruses and includesLTR-flanked regions, including three retroviral ORFs: pol-pro, env and gag . In thecourse of evolution, the specific ERV Ty3/gypsy has becomethe source of Arc protein. This protein is similar in biologicalproperties to the gag retroviral gene expression product.Since domestication and use for the needs of the host, theArc gene has become highly conserved for vertebrates, playinga role in the functioning of their brain. Expression of Arc ishighly dynamic in the brain in accordance with the encodingof information in neural networks. Arc gene transcript is transportedto dendrites and accumulates in areas of local synapticactivity, where translation into protein occurs . In neurons, the Arc protein forms spatial structuresresembling viral capsids that encapsulate cell mRNA. The resultingvirus-like elements in the composition of extracellularvesicles are transmitted to neighboring neurons, where theyare able to translate. This phenomenon is used to consolidate long-term memory , in the formationof which the hippocampus is involved, where the maximumactivity of TEs is detected .Based on the data listed above, it can be concluded that theobserved phenomenon of intercellular neuronal interconnectionusing Arc has developed in evolution as a reflection ofthe adaptive value of the TE transcript transfer phenomenonbetween postmitotic cells. It is possible that when neurons exchangevirus-like mRNA particles between neurons, the abilityof TEs to be integrated in a site-specific manner with a change in the expression of neuron-specificgenes is used to form long-term memory. As a result, thefunctioning of neurons and the storage of information in thebrain change .Transposable elements transpositions affect gene expressionin various ways. Insertions within a gene can cause frameshiftmutations, premature stop codons, or exon skipping. In thetranscribed portion of the gene, TEs can reduce mRNA levelsby slowing transcription due to the high A/T content in ORF2of TEs such as L1 RE . However,despite the potentially mutagenic effect TEs play a role in theevolution of the genomes of all eukaryotes through the use ofTE sequences to form host adaptive abilities . TEs are involved in controlling the expressionof protein-coding genes, many of which , including transcription factors ,originated from TEs. In addition to the direct domesticationof TEs, new protein-coding genes were formed due to exonizationand duplication of genes using TEs .Mechanisms derived from TEs are used by the mammalianimmune system to generate antibodies using the V(D)J recombinationsystem. TEs are the source of most steroid receptors,participating in the global regulation of cell function by thehormonal system . Regulatory sequences,silencers, and insulators evolved from TEs . If TEs are insertedinto non-coding regions of genomes, they are used as alternativepromoters, enhancers, and polyadenylation signals ofgenes. For example, L1s are found in non-coding regions of80 % of human genes, the expression pattern of which dependson the density of these REs .About 60 % of all SVAs in the human genome are locatedin the genes or flank them within 10 kb. These SVAs arecharacterized as mobile CpG islands capable of upstreamor downstream regulation of gene expression by recruitingtranscription factors. In addition, due to the high GC content,SVAs can form alternative DNA structures, such as the G- quadruplex(characteristic of promoters of 40 % of human genes),which affects transcription . Manytranscription factors are immediately directed to the relationshipwith TEs, forming and maintaining heterochromatin. TEs serve as sources of cis- and transregulatoryelements that coordinate the expression of groupsof genes. In addition to acting as promoters that control theexpression of alternative host gene isoforms, TFBS within TEs can act as enhancers in certain tissues and at certain stages ofdevelopment .In evolution, \u0422\u0415s were the sources of a significant part of the specific sequences of the genome, as well as transcripts andproteins interacting with them. This indicates a global regulatoryrole of TEs, necessary for both mitosis and meiosis, andfor controlling the work of cells in interphase. For example,not only spliceosomal introns ,but also the Prp8 spliceosome component originated fromTEs . Splicing enhancers and silencers are10-nucleotide-long ncRNAs that interact with SR proteinsand snRNAs. They are formed by processing transcripts ofAlu retroelements . TEs turned out to besources of satellites due to the capability of site-specific insertions and illegitimate recombination,followed by amplification by gene conversion . In evolution, TEs have become sources of telomeraseand telomeres , as well as centromeresand the protein CENP/CENH3 interacting with them . Small ncRNAs formedupon transcription of centromeric REs are involved in theregulation of these interactions .Less than 1.2 % of the human genome is responsible for thecoding of proteins. The remaining non-coding part of thegenome was largely formed due to TEs. The data on the participationof TEs in the regulation of gene switching during celldifferentiation in embryogenesis, starting with the first zygotedivision, suggest that somatic mosaicism observed in neuronsreflects the active role of TEs in neurogenesis. A number ofpapers have been published proving the participation of TEsin the control of differentiation of neurons. Transposableelements are sources of ncRNA, which are also importantin gene switching in brain cells. The revealed role of LTRcontainingREs in the exchange of transcripts between neuronsmay reflect the general principle of the participation of TEsin the regulation of gene expression for the development andmaintenance of brain function. The use of Arc protein for theformation of virus-like particles in the transfer of informationbetween cells indicates the evolutionary mechanismsof TE conversion into viruses for the formation of adaptivefunctions. This mechanism is associated with the use of TEsto ensure the dynamism of the genomes of postmitotic cellswith the possibility of their adaptive changes in response toenvironmental influences. The realization of this phenomenonis possible due to reverse transcription of mRNA transportedbetween cells with site-specific insertions, the formation ofsomatic mosaicism of mature neurons, and a change in geneexpression for memory consolidation.The authors declare no conflict of interest.Since somatic mosaicism cannot be inherited, the functionalrole of TE insertions in neurogenesis is difficult toprove. Moreover, these changes can be characterized asrandom events that are more important for the developmentof neurological disorders. However, the data presented inthe review prove the importance of TE transpositions intofunctionally significant regions of the genome, which arenecessary for differentiation of neuronal stem cells and theresponse to environmental influences. The explanation of this regular phenomenon is the capability of TEs to be insertedin a site-specific manner programmed by their own positionin the genome. These nonrandom events are selectedduring the evolution of multicellular organisms, promotingregulatory regulation of gene expression during cell differentiation.The results obtained on the importance of TE transpositionsin neurogenesis reflect one of the stages of regulation of geneexpression in successive cell divisions during differentiation oftissues and organs of the whole organism. Somatic mosaicismin neurons and stem cells is in favor of this assumption, sincethe brain is characterized by a pronounced variety of cell types,for the specific tuning of gene expression of which universalcombinatorial units, such as TEs, are required.Allen Brain Atlas. Available at: www.brain-map.orgAprea J., Prenninger S., Dori M., Ghosh T., Monasor L.S., WessendorfE., Zocher S., Massalini S., Alexopoulou D., Lesche M.,Dahl A., Groszer M., Hiller M., Calegari F. Transcriptome sequencingduring mouse brain development identifies long non-codingRNAs functionally involved in neurogenic commitment. 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C.S. conceived and was responsible for the study and R.C. developed and enhanced it, performing most of the experiments, including sample preparation for proteomics, and took the lead in writing the manuscript in consultation with C.S. The latter was reviewed by all authors with critical feedback with final revision and approval by C.S.\u201dnow reads:\u201cL.M.C. and Z.C. contributed to sample preparation and experiments. P.F-T. helped with, and C.R. was responsible for, the proteomic data analysis. C.S. conceived and was responsible for the study and R.C. developed and enhanced it, performing most of the experiments, including sample preparation for proteomics, and took the lead in writing the manuscript in consultation with C.S. The latter was reviewed by all authors with critical feedback with final revision and approval by C.S.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Broadening of the genetic diversity of donors of resistance to biotic environmental factors is a challengingproblem concerning Triticum L., which can be solved by using wild relatives of wheat, in particular, Aegilopstauschii Coss., in breeding programs. This species, believed to be the donor of D genome of common wheat(T. aestivum L.), is a source of some traits important for breeding. This greatly facilitates the possibility of crossingAe. tauschii with common wheat. Aegilops L. species are donors of effective genes for resistance to fungal diseasesin wheat. For instance, genes that determine resistance to rust agents in common wheat were successfullyintrogressed from Ae. tauschii into the genome of T. aestivum L. The aim of our study was to identify differencesin metabolomic profiles of Ae. tauschii forms (genotypes), resistant or susceptible to such fungal pathogens asPuccinia triticina f. sp. tritici and Erysiphe graminis f. sp. tritici. These indicators may be used as biochemical markersof resistance. A comparative analysis of groups of Ae. tauschii accessions showed that metabolomic profiles of theforms with or without resistance to fungal pathogens differed significantly in the contents of nonproteinogenicamino acids, polyols, phytosterols,acylglycerols, mono- and oligosaccharides, glycosides, phenolic compounds, etc. This fact was consistent with the previously obtained data on the relationshipbetween Fusarium resistance in oats (Avena sativa L.) and certain components of the metabolomic profile, such asacylglycerols, nonproteinogenic amino acids, galactinol, etc. Thus, our studies once again confirmed the possibilityand effectiveness of the use of metabolomic analysis for screening the genetic diversity of accessions in the VIRcollection, of Ae. tauschii in particular, in order to identify forms with a set of compounds in their metabolomicprofile, which characterize them as resistant. Ae. tauschii accessions with a high content of pipecolic acids, acylglycerols,galactinol, stigmasterol,glycerol, azelaic and pyrogallic acids, campesterol, hydroquinone, etc., can beused for creating wheat and triticale cultivars with high resistance to fungal pathogens causing powdery mildew,brown rust, and yellow rust. Wheat (Triticum L.) is one of the most significant crops inthe world, including the Russian Federation. For the majorityof the world\u2019s population, it is one of the staple foods. Theyield and quality of wheat largely depend on the resistanceof cultivars to environmental stress factors, including fungaldiseases. Most of the cultivated foreign and domestic cultivarsare susceptible to diseases caused by agents of stem rust(Puccinia graminis Pers. f. sp. tritici Erikss. et Henn), brownrust (Puccinia recondita Rob. ex Desm f. sp. triticina Eriks.),mildew (Blumeria graminis (DC.) Speer f. sp. tritici Marchal.)and septoria leaf blotch (Mycosphaerella graminicola (Fuckel)J. Schroet. (=Septoria tritici); Phaeosphaeria nodorum(E. Muell.) Hedjar. ). Crop losses can reach up to 40 %. The creation ofwheat cultivars resistant to the most harmful fungal pathogensis one of the effective ways to combat them.Wild relatives of cultivated forms of wheat, rye, barley,oats, etc. serve as an inexhaustible source of resistance genesfor creating cultivars combining high yields and resistanceto environmental factors. Evolutionary, Aegilops L. speciesare close to those of the genus Triticum L. . However, the donors used in breeding programs,in most cases are characterized by the same resistance genes.With time, it leads to the appearance of \u201cadapted\u201d forms ofpathogens that infect cultivars previously considered to be resistant.Many known resistance genes from Ae. tauschii Coss.are not used in practice to improve wheat cultivars, as theirprotective effect is considered low . Expansion of the genetic diversity of donorsof resistance to wheat fungal diseases will help breederssolve this problem, and the global collection of wheat wildrelatives at the N.I. Vavilov All-Russian Research Institute ofPlant Industry (VIR) plays a crucial role in this task .The VIR collection of the genus Aegilops L. contains over5,000 accessions of various ecological and geographical origins,and it includes thirteen diploid, ten tetraploid, and fivehexaploid species. Since 1956, species possessing compleximmunity to fungal diseases have been identified in the collection:diploid Ae. mutica Boiss., Ae. speltoides Tausch.,Ae. aucheri Boiss., Ae. bicornis (Forsk.) Jaub. et Spach.,Ae. comosa Sibth. & Sm., Ae. uniaristata Vis., Ae. heldreichiiHozm.; tetraploid Ae. ovata L., Ae. triaristata Wild., Ae. ventricosaTausch., Ae. variabilis Eig. Such a diversity of geneticmaterial makes it possible to select appropriate genotypes forthe subsequent production of wheat cultivars with improvedbiological characteristics. Ae. tauschii is a carrier of D genome,which is close to the polyploid wheat genome, andthis fact greatly facilitates the crossing of Ae. tauschii withcommon wheat when transmitting effective disease resistancegenes . Besides, flour of suchcultivars has high baking quality .By now, most of the effective genes that determine resistanceto rust and wheat spot blotch agents have been successfullyintrogressed into the genome of T. aestivum L. .Recently, nonspecific metabolomic analysis has found wideapplication for plant species phenotyping and resistance studies,which provides a unique opportunity to scan a wide rangeof compounds that make up the metabolomic profile in thesource material and give an objective assessment (using metabolomicmarkers) of the plant\u2019s response to environmentalfactors . This approach is increasinglyused to identify individual metabolites or their groups thatcan characterize the protective status of the studied object,which makes it possible to identify accessions resistant toenvironmental stressors .Currently, metabolomic profiles of various crops from theVIR collection are investigated. Wild and cultivated forms ofoats resistant and susceptible to Fusarium were studied, andsignificant differences among them were shown for a numberof compounds . Total screeningof wild forms of various crops will make it possible to shapea model \u201cmetabolomic profile of a resistant cultivar\u201d.The aim of this study was the identification of metabolomicmarkers to be used in screening the genetic diversity of wildrelatives for the forms with effective resistance genes, whichcan be efficiently introduced into the common wheat genome for the use in breeding programs. The research objectivesincluded the study of metabolomic profiles of Ae. tauschii accessionswith and without resistance to leaf rust and powderymildew pathogens, in order to detect metabolites marking thesusceptibility of Ae. tauschii to fungal pathogens. The resultsof the study can shorten and optimize the selection of sourcematerial when creating wheat cultivars highly resistant tofungal pathogens.Fifty Ae. tauschii accessions from the VIR collection (see theTable), grown at the Dagestan Experimental Station of VIR(DES VIR) in 2017 and harvested at full ripeness, were usedas the material for the study. The sample was composed fromthe main of Ae. tauschii botanical varieties in the VIR collection,taking into account the most complete ecogeographicalrepresentation.2 plots according to the methodaccepted in VIR . During the growingseason, the air temperature averaged +20.4 \u00b0C, the amount ofprecipitation was 15.4\u201316.3 mm, and the total of active temperaturesamounted to 3400\u20134500 \u00b0\u0421. Field assessment of theinfection of Ae. tauschii accessions by fungal pathogens wascarried out in fields of DES VIR, and the laboratory evaluationof the degree of infection was carried out at the VIR Departmentof Genetics in compliance with methods employed atVIR . Resistance was determined on a9-point scale, where 9 means the absence of disease symptomsor presence of small necrotic spots; 7, microscopic pustulessurrounded by necrotic zone; 5, small pustules surrounded bya wide necrotic zone; 3, medium-size pustules surrounded bychlorotic tissue; and 1, large pustules forming continuous lesionzones. Plants scoring 9\u20137 were classified as resistant, andthose with 5\u20131 points as susceptible. Plants were examinedat 5-day intervals throughout the growing season. For eachaccession, an integral score was derived from the highestinfection point (see the Table).Field studies of Ae. tauschii accessions were conductedat DES VIR on irrigated 1-Metabolomic profiles of grain from Ae. tauschii accessionswere studied at the Department of Biochemistry and MolecularBiology of VIR . The grains were cleaned of glumes andground; 50 mg of the flour of an accession were homogenizedwith 500 \u03bcL of methanol, and the sample was kept at 5\u20136 \u00b0Cfor 30 days. A 100-\u03bcL portion of the extract was evaporatedto dryness using a Labconco CentriVap Concentrator (USA).The dry residue was silylated using bis(trimethylsilyl)trifluoroacetamideat 100 \u00b0C for 40 minutes. The separationof trimethylsilyl ethers of metabolites was carried out usingan HP-5MS 5 % phenyl\u201395 % methylpolysiloxane capillarycolumn on an Agilent 6850gas chromatograph with an Agilent 5975B VL quadrupolemass selective detector MSD .The analysis was performed at 1.5 mL/min inert gas flowrate through a column. The column was heated from +70up to +320 \u00b0C at 4 \u00b0C/min heating rate. The temperature ofthe mass spectrometer\u2019s detector was +250 \u00b0C, and that ofthe injector was +300 \u00b0C. The injected sample volume was 1.2 \u03bcL. Pyridine solution of tricosan (1 \u03bcg/\u03bcL) served as theinternal standard.The results were processed using UniChrom and AMDISsoftware. The peaks were identified using the NIST 2010 massspectra library and as well as libraries of the St. PetersburgUniversity Research Park and of the V.L. Komarov BotanicalInstitute of the Russian Academy of Sciences . The biochemical parameter values are given inppm (\u03bcg/g).Statistical data were evaluated with the Statistica 7.0 softwarepackage. The initial set of characters was screened bythe method of one-way analysis of variance to identify thecharacters (metabolites) whose contents reliably discriminatedAe. tauschii accessions resistant and susceptible to thestudied pathogens. The discriminant analysis was used toassess informativeness of resistance characters (metabolites)of Ae. tauschii accessions.Metabolomic profiles of caryopses of Ae. tauschii accessionswith and without resistance to fungal pathogens differed inseveral indicators. Higher contents of organic acids wereobserved in the resistant forms of Ae. tauschii (1190 ppm)compared with the susceptible ones (1090 ppm). The dominatingorganic acids in the metabolomic profile of Ae. tauschiicaryopses were malic and methylmalonic acids . The caryopses of resistantand susceptible forms were found to contain, respectively, thefollowing contents of organic acids (ppm): 102 and 79 galacturonicacid, 78 and 76 lactic, 43 and 48 gulonic, 25 and44 gluconic, 30 and 47 azelaic, 32 and 38 succinic, 28 and27 oxalic, 42.8 and 41.0 fumaric, 19.9 and 13.0 ribonic, and11.5 and 10.0 glyceric. The sum of minor acids with concentrationsno higher than 10 ppm each was 24.0 ppm in bothresistant and susceptible forms of Ae. tauschii. All metabolicreactions in plants occur with the participation of phosphoricacid and its derivatives, which explains its rather high contentin the studied accessions (320.2 in resistant and 277.0 ppmin susceptible forms), the amounts of methylphosphate being64.0 and 56.0 ppm, respectively.Three nonproteinogenic amino acids constituted 60 %of free amino acids in resistant and susceptible Ae. tauschiiaccessions: 3-hydroxypipecolic (137.2 and 116.6), pipecolic(0.5 and 0.3), and 5-hydroxypipecolic .The remaining amino acids were representedby essential and non-essential ones . The dominating oneswere asparagine (18.7 and 13.4 ppm), valine (15.6 and 16.0),\u03b1-alanine (10.6 and 13.1), glutamine (12.3 and 9.0) and glutamicacid (5.7 and 5.5 ppm), respectively. The amounts ofthe remaining amino acids did not exceed 4.0 ppm. The sumsof free amino acids (except nonproteinogenic) did not differsignificantly between the studied forms of Aegilops resistantand susceptible to fungal pathogens: 88.4 and 85.3 ppm, respectively.Higher concentrations of polyols and phytosterols wererecorded in the susceptible forms of Ae. tauschii . Glycerol, xylitol, dulcitol, myo-inositoland inositol derivatives prevailed in caryopses of the susceptible forms,while galactinol (92.5 ppm) dominated in the resistant ones.Phytosterols were mainly represented by sitosterol, stigmasterol,and campesterol; their contents were 219.8, 85.8,and 30.9 ppm in the susceptible forms, and 160.3, 44.5, and22.7 ppm in the resistant ones, respectively.The dominating fatty acids in caryopses of both resistantand susceptible forms of Ae. tauschii were palmitic (584.7 and602.0), stearic (173.5 and 187.0), oleic (493.9 and 520.0), andlinoleic (1515.0 and 1545.0 ppm), respectively. No significantdifference in the contents of individual fatty acids or their totalvalues (2943.3 and 3064.0 ppm) was noted.The caryopses of resistant forms of Ae. tauschii were foundto have higher contents of acylglycerols (954.0 vs. 745.6 ppm),mainly due to diacylglycerol (DAG) amounting to 631.0 and464.0 ppm, respectively. The amounts of monoacylglycerols,i. e., MAG-2 C18:3 and MAG-1 C18:1, were also higher inresistant forms: 188.0 vs. 152.7, 54.0 vs. 34.2 ppm. \u041en thecontrary, the content of MAG-1 C16:0 was higher in the susceptibleforms: 94.7 vs. 81.0 ppm in resistant.Monosugars in Ae. tauschii caryopses were representedmainly by hexoses (over 80 %). These values were higher(1164.8 ppm) for resistant forms of Aegilops than for susceptibleones (1026.7 ppm). Of the hexoses, glucose (819.8)was predominant in resistant forms, while in the susceptibleones these were glucose (455.4) and fructose (318.1 ppm).The total pentose contents (ribose and xylose) did not exceed40 ppm. The contents of glycerol-3 phosphate did not differsignificantly between resistant and susceptible forms ofAegilops. They amounted to 42.8 and 37.4 ppm, respectively.Oligosaccharides in caryopses of resistant and susceptibleforms of Ae. tauschii amounted to 13480.6 and 14920.0 ppm,respectively. They were mainly represented by sucrose and raffinose.The content of sucrose was higher in susceptible forms(11604.9), while that of raffinose was higher (4882.0 ppm) inresistant ones.Derivative sugars, identified as methyl-D-galactopyranoside,were found in both resistant and susceptible forms ofAe. tauschii .In the group of phenolic compounds, the contents of hydroquinone(93.6 in resistant and 74.0 ppm in susceptibleaccessions) were found to be the highest. The values forkempferol; pyrogallic, 2,3-dihydroxybenzoic, salicylic, andcaffeic acids; and \u03b1-tocopherol were 29.1, 1.5, 0.2, 0.3, 0.4,0.4 ppm in resistant and 14.0, 1.3, 0.2, 0.2, 0.4 and 0.3 ppmin susceptible forms.The above data reflect the activity of metabolic processes inAe. tauschii caryopses. This activity characterizes primary andsecondary metabolism, i. e., exchange of nitrogen-containingcompounds, including amino acids; the Krebs cycle; carbohydratemetabolism; glycolysis; pentose phosphate cycle;exchange of signal (inositol) compounds; shikimate and glyoxylatepathways; etc.Statistical processing of the data showed that the metabolomeof susceptible forms of Ae. tauschii differs with varyingdegrees of significance from that of resistant ones in a numberof indicators. Resistant forms of Ae. tauschii were divided into three groups: the first comprised accessions resistant to all thepathogens tested, the second included those resistant to onlybrown and yellow leaf rust, while the third included mildewresistant accessions. The metabolomes of all resistant formsdiffered with a high degree of confidence ( p = 0.05) fromthose of susceptible ones in the contents of nonproteinogenicamino acids (pipecolic and 3-hydroxypipecolic), glycerol,ononitol, galactinol, sitosterol, stigmasterol, behenic acid,DAG, MAG-1 C16:1, ribose, sorbose, sucrose, maltose, andhydroquinone; and with confidence levels 0.1 > p > 0.05 forfumaric, galacturonic, gluconic acids, threonine, dulcitol,mannitol, chiro- and myo-inositol, pelargonic and arachinicfatty acids, MAG-1 C18:1, and fructose. At p = 0.05, metabolomesof accessions from the second group differed inthe content of the phosphoric, oxalic, pyrogallic, azelaic,5-hydroxypipecolic acids; dulcitol; campesterol; undecyl andbehenic fatty acids; and MAG-1 C18:1; while lower confidencelevels (0.1 > p > 0.05) characterized the differences inthe contents of 3-hydroxypipecolic acid, MAG-2 C18:3, andmethyl-D-galactopyranoside. The third group was noted forthe amounts of fumaric, pelargonic, pipecolic acids, ononitol,galactinol, and hydroquinone at p = 0.05, and for threonine,dulcitol, myoinositol, hydroxyoctacosenoic acid, and sucroseat 0.1 > p > 0.05.A significant correlation was found between indicatorsof resistance to fungal pathogens and the group of nonproteinogenicamino acids, polyols, phytosterols, acylglycerols,mono- and oligosaccharides, glycosides, and phenoliccompounds . No relationship wasfound between the sum of free amino acids and organic acids,on the one hand, and sensitivity to fungal pathogens, on theother hand.The discriminant analysis of metabolomic data on thestudied caryopses of Ae. tauschii accessions demonstratedseparation of the latter into two main groups \u2013 resistant andsusceptible to fungal pathogens \u2013 according to the canonicalvariable coefficient. The most \u201cinformationally important\u201dcharacters that confirmed the difference in metabolite profilesand determined the separation of Ae. tauschii accessionsbetween the group of resistant or susceptible ones with the98 % accuracy were the levels of stigmasterol, MAG, DAG;of pelargonic, galacturonic, and 3-hydroxypipecolic acids;and of galactinol, glycerol, sorbose, maltose, tyrosine andglycosides. Among the above characters, stigmasterol andmaltose values were the most statistically significant for thesusceptible forms, while for the resistant ones it was DAG.The \u201cinformationally important\u201d characters and the classificationfunction were used to analyze how the assumptionsas for the resistance or susceptibility of Ae. tauschii accessionsmatched the reality. As a result, the status was confirmed forall the studied accessions, except for k-527, an Ae. tauschiiaccession from Armenia. The canonical discriminant analysisof metabolomic characters made it possible to clarify the differentiationparameters of resistant and susceptible forms ofAe. tauschii. The histogram of the canonical variable eigenvaluesdistribution according to their magnitude shows thatthe values for resistant accessions fall within the 0 to +5 range,while for the susceptible ones these values are found in the 0to \u20135 range .The results of our work show that the metabolomic profiles ofresistant and susceptible forms of Ae. tauschii differ significantly.When using the metabolomic analysis data, there is ahigh probability (up to 98 %) of identifying forms resistant tofungal pathogens among the accessions taken into the studywithout additional tests. We recommend that this approach beused to optimize the breeding process.Analysis of metabolomic data for resistant and susceptibleforms of Ae. taushii allows for a substantiated conclusionabout the degree and nature of fungal pathogen influenceon the main stages of primary and secondary metabolism incaryopses of accessions differing in the degree of resistance.To a greater or lesser degree, almost all pathogens affectedmetabolic processes, i. e., the Krebs cycle; glycolysis; andmetabolism of fatty acids, acylglycerols, polyols, phytosterols,mono- and oligosaccharides. With all this, fungal pathogenshad practically no effect on the contents of free amino acids(except for threonine and tyrosine). Since tyrosine is a precursorin the synthesis of many bioactive compounds that performvarious functions \u2013 structural (lignin), protective , transport (electron transfer),and others \u2013 the effect of pathogens on the content of thisamino acid in a caryopsis may be due to activation of defensemechanisms in response to the penetration of the pathogeninto plant tissues, as confirmed by studies conducted outsideRussia . Changes in the content ofanother amino acid, threonine, are associated by a numberof authors with the influence of adverse biotic environmentalfactors, for example, insect pests. A plant reduces the concentrationof substances necessary for the nutrition of the parasite,thereby affecting its population. The same mechanism mayalso act in cases of leaf rust and powdery mildew pathogens. Azelaic acid, a product of oleicacid oxidation, and pipecolic acid (lysine catabolites) areintensely produced in response to the invasion of pathogens,in particular, fungi, into plant tissues; therefore, changes inthe concentration of these compounds are well justified and confirmed by other researchers .Among free phenolic compounds, a significant effect on theresistance to fungal pathogens was detected for hydroquinone(the dominant compound of this group) and pyrogallic acid.Phenolic compounds are known to be actively involved inthe formation of plant immunity. The presence of free formsof phenolic compounds most often indicates intensity ofglycoside synthesis, where they function as aglycones. Accordingto our data, mainly hydroquinone and pyrogallic acidaccumulate in the caryopsis of resistant forms of Ae. tauschii.Their presence in the free state is most likely associated withthe destruction of active forms, glycosides, exemplified byarbutin. As for pyrogallic acid, its accumulation may also bedue to the plant/fungal pathogen interaction .The data from the present study confirm those we obtainedearlier investigating the relationship between the resistance ofoat (Avena sativa L.) forms to the Fusarium agent and suchcomponents of the metabolomic profile as acylglycerols,nonproteinogenic amino acids, and galactinol .The results of our study confirm the pertinence and effectivenessof the use of nonspecific metabolomic analysis for thesearch for and identification of plant forms with a set of compoundsproposed as markers of resistance to certain pathogens.Ae. tauschii accessions with high contents of pipecolic acids,acylglycerols, galactinol, stigmasterol, maltose, tyrosine,sorbose, glycerol, azelaic and pyrogallic acids, methyl-Dgalactopyranoside,etc. can be included in breeding programsfor cultivars of main cereal crops with high resistance tomildew, brown rust, and yellow rust.The authors declare no conflict of interest.Adonina I.G., Petrash N.V., Timonova E.M., Christov Yu.A., SalinaE.A. Construction and study of leaf rust resistant commonwheat lines with translocations of Aegilops speltoides Tausch.geneticmaterial. Russ. J. Genet. 2012;48:404-409. DOI 10.1134/S1022795412020020.Afanasenko O.S. Problems of creating cultivars with long-term diseaseresistance. Zaschita i Karantin Rastenii = Plant Protectionand Quarantine.2010;3:4-10. (in Russian)Arora S., Singh N., Kaur S., Bains N.S., Uauy C., Poland J., ChhunejaP. Genome-wide association study of grain architecture inwild wheat Aegilops tauschii. Front. Plant Sci. 2017;8:886. DOI10.3389/fpls.2017.00886.Chakraborty S., Newton A.C. Climate change, plant diseases andfood security: an overview. Plant Pathol. 2011;60:2-14. DOI10.1111/ j.1365-3059.2010.02411.x.Dobrotvorskaia T.V., Martynov S.P., Chikida N.N., MitrofanovaO.P. Wheat cultivars and lines whose pedigrees includeAe. tauschii Coss. In: Catalogue of the VIR Global Collection.St. Petersburg, 2017;842:47. (in Russian)Dorofeev V.F. Remote Hybridization and the Origin of Wheat.Leningrad,1971. (in Russian)Gilbert K. Plant Secondary Metabolism. Seigler David S. PlantGrowth Regul. 2001;34(1):149-149. DOI 10.1023/A:1013354907356.Gonzales-Vigil E., Bianchetti Ch.M., Phillips G.N., Jr., Howe G.A.Adaptive evolution of threonine deaminase in plant defenseagainst insect herbivores. Proc. Natl. Acad. Sci. USA. 2011;108(14):5897-5902. DOI 10.1073/pnas.1016157108.Kolmer J.A., Anderson J.A. First detection in North America of virulencein wheat leaf rust (Puccinia triticina) to seedling plantsof wheat with Lr21. Plant Dis. 2011;95:1032. DOI 10.1094/PDIS-0411-0275.21.Kolomiets T.M., Pankratova L.F., Pakholkova E.V. Wheat (TriticumL.) cultivars from GRIN collection (USA) selected for durableresistance to Septoria tritici and Stagonospora nodorumblotch. SelskokhozyaystvennayaBiologiya = Agricultural Biology.2017;52(3):561-569. 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DOI 10.15389/agrobiology.2019.3.575eng.Loskutov I.G., Shelenga T.V., Konarev A.V., Shavarda A.L.,Blinova E.V., Dzubenko N.I. \u0422he metabolomic approach tothe comparative analysis of wild and cultivated species of oats(\u0410vena L.). Russ. J. Genet.: Appl. Res. 2017;7(5):501-508. DOI10.1134/S2079 059717050136.McIntosh R.A., Wellings C.R., Park R.F. Wheat Rust: An Atlas ofResistance Genes. Australia: CSIRO Publ., 1995.Merezhko A.F., Udachin R.A., Zuev E.V., Filatenko A.A., SerbinA.A., Liapunova O.A., Kosov V.I., Kurkiev U.K., OkhotnikovaT.V., Navruzbekov N.A., Boguslavskii R.L., Abdulaev A.K.,Chikida N.N., Mitrofanova O.P., Potokina S.A. Enriching, ConservingViable, and Studying the Global Collections of Wheat,Aegilops, and Triticale. St. Petersburg, 1999. (in Russian)Migushova E.F. On the origin of wheat genomes. Trudy po PrikladnoyBotanike, Genetike i Selektsii = Proceedings on AppliedBotany, Genetics, and Breeding. 1975;55(3):3-26. (in Russian)Mujeeb-Kazi A., Cano S., Rosas V., Cortes A., Delgado R. Registrationof five synthetic hexaploid wheat and seven bread wheatlines resistant to wheat spot blotch. Crop Sci. 2001;41(5):1653-1654. DOI 10.2135/cropsci2001.4151653x.Navarova H., Bernsdorff F., Doring A.C., Zeier J. Pipecolic acid,an endogenous mediator of defense amplification and priming,is a critical regulator of inducible plant immunity. Plant Cell.2012;24(12):5123-5141. DOI 10.1105/tpc.112.103564.Pretorius Z.A. Detection of virulence to Lr41 in a South Africanpathotypeof Puccinia recondita f. sp. tritici. Plant Dis. 1997;81(4):423. DOI 10.1094/PDIS.1997.81.4.423A.Puzanskiy R.K., Shavarda A.L., Tarakhovskaya E.R., Shishova M.F.Analysis of metabolic profile of Chlamydomonas reinhardtii cultivatedunder autotrophic conditions. Appl. Biochem. Microbiol.2015;51(1):83-94. DOI 10.1134/S0003683815010135.Schenck C.A., Maeda H.A. Tyrosine biosynthesis, metabolism, andcatabolism in plants. Phytochemistry. 2018;149:82-102. DOI10.1016/ j.phytochem.2018.02.003.Semenova L.V., Migushova E.F., Devjatkina E.P. Grain quality ofAegilopsgrain, ancestor of wheat. Trudy po Prikladnoy Botanike,Genetike i Selektsii= Proceedings on Applied Botany, Genetics,and Breeding. 1973;50(1):216-226. (in Russian)Taji T., Takahashi S., Shinozaki K. Inositol and their metabolism inabiotic and biotic stress responses. Subcell. Biochem. 2006;39:239-264. DOI 10.1007/0-387-27600-9_10.Tyryshkin L.G., Kolesova M.A., Chikida N.N. Aegilops tauschiiCoss. Characteristics of accessions for juvenile leaf disease resistance.In: Catalogue of the VIR Global Collection. St. Petersburg,2004;763:3-15. (in Russian)Valitova J.N., Sulkarnayeva A.G., Minibayeva F.V. Plant sterols:diversity, biosynthesis, and physiological functions. Biochemistry(Moscow). 2016;81(8):819-834. DOI 10.1134/S0006297916080046.Vavilov N.I. Plant Immunity to Infectious Diseases. Moscow, 1919.(in Russian)Yang W.-Y., Yu Y., Zhang Y., Hu X.-R., Wang Y., Zhou Y.-C.,Lu B.- R. Inheritance and expression of stripe rust resistance incommon wheat (Triticum aestivum) transferred from Aegilopstauschii and its utilization. Hereditas. 2003;139:49-55. DOI10.1111/j.1601-5223. 2003.01671.x.Zoeller M., Stingl N., Krischke M., Fekete A., Wallter F., BergerS.Lipid profiling of the Arabidopsis hypersensitive response revealsspecific lipid peroxidation and fragmentation processes:biogenesis of pimelic and azelaic acid. Plant Physiol. 2012;160(1):365-378. DOI 10.1104/pp.112.202846."} +{"text": "One of the key smart city visions is to bring smarter transport networks, specifically intelligent/smart transportation. It facilitates safe and effective physical movement and interaction of humans, animals, and goods. Typical global issues include sustainable energy, traffic accidents, traffic congestion, logistic management, data analysis, security, and privacy. In recent years, the internet-of-things (IoT) and artificial intelligence (AI) have taken a leading role in achieving this smart city vision. The former provides a solid infrastructure for scalable and robust data collection and transmission. The latter brings creative and innovative elements to machines for intelligent transportation applications. In this special issue, \u201cInternet of Things and Artificial Intelligence in Transportation Revolution\u201d, ten (10) research articles have been published. These articles generate a meaningful discussion around the impacts of AI and IoT in intelligent transportation. This editorial not only summarizes the special issue articles but also shares other hot research topics.Transportation plays an essential role in today\u2019s economic and social development. As daily road users, we need to ensure safe and effective travel. According to the World Health Organization (WHO), annual road traffic deaths and injuries reach 1.35 million and 50 million, respectively [The first article, \u201cDecision-making for the autonomous navigation of maritime autonomous surface ships based on scene division and deep reinforcement learning\u201d authored2. Results showed that half of the data points were perfect, whereas 90% of the data points were deviations by two cells.Y. Jiang, B. Liu, Z. Wang, and X. Yi presented an article \u201cStart from scratch: A crowdsourcing-based data fusion approach to support location-aware applications\u201d . Multi-dIn , G. BaldOptimization of vehicle arrival time and signal timings is vital for traffic signal control. W. Wu, L. Huang, R. Du, presented an article \u201cSimultaneous optimization of vehicle arrival time and signal timings within a connected vehicle environment\u201d . A time-In , S. Guo,Another work, \u201cA generic design of driver drowsiness and stress recognition using MOGA optimized deep MKL-SVM\u201d authored by K. T. Chui, M. D. Lytras, and R. W. Liu , presentY. Guo, B. Li, M. D. Christie, Z. Li, M. A. Sotelo, Y. Ma, and Z. Li published an article \u201cHybrid dynamic traffic model for freeway flow analysis using a switched reduced-order unknown-input state observer\u201d . DynamicIn , an artiThe article \u201cVision-Based Machine Learning Method for Barrier Access Control Using Vehicle License Plate Authentication\u201d published in this special issue is authored by K. T. Islam, R. G. Raj, S. M. Shamsul Islam, S. Wijewickrema, M. S. Hossain, T. Razmovski, S. A. O\u2019Leary . An artiFinally, G. Baldini, R. Giuliani, and F. Geib presented an article \u201cOn the application of time frequency convolutional neural networks to road anomalies identification with accelerometers and gyroscopes\u201d . It propIn 2015, all United Nations member states agreed to build strong partnerships to meet 17 sustainable development goals (SDGs) and 169 targets . Among aVarious emerging key applications are suggested for exploration. A study has applThe guest editors would like to thank the contributions of all colleagues and reviewers. We are grateful for your support."} +{"text": "Megophryssensu lato as a diverse group was proposed to contain dozens of cryptic species. Based on molecular phylogenetics, morphology, osteology, and bioacoustics data, the species profiles of Megophrys toads in the eastern corner of Himalayas in Medog County, Tibet Autonomous Region, China was investigated. The results indicated that this small area harbored at least four Megophrys species, i.e., M.medogensis, M.pachyproctus, Megophryszhouisp. nov., and Megophrysyeaesp. nov., the latter two being described in this study. Additionally, the mitochondrial DNA trees nested the low-middle-elevation and high-elevation groups of M.medogensis into a monophyletic group, being in discordance with the paraphyletic relationship between them revealed in the nuclear DNA trees. The findings highlighted the underestimated biodiversity in Himalayas, and further indicated that the Megophrys toads here have been probably experienced complicated evolutionary history, for example, introgression between clades or incomplete lineage sorting and niche divergences in microhabitats. Anyway, it is urgent for us to explore the problems because these toads are suffering from increasing threats from human activities and climatic changes.Multiple disciplines can help to discover cryptic species and resolve taxonomic confusions. The Asian horned toad genus Species are the basic units of biodiversity, and species taxonomy is central to biodiversity explorations, further contributing to evolutionary biology, conservation biology and other categories of biological studies . IncreasMegophryssensu lato Kuhl and Van Hasselt, 1822 widely inhabit mountain forests in the tropical and subtropical regions of Asia, ranging from India to south-central China and south to the Sundas and the Philippines based on morphology. Megophryscf.pachyproctus was defined because the specimens were collected from the type locality of M.pachyproctus , and they are morphologically similar to the holotype of M.pachyproctus although with some morphological differences. For caution, we regarded M.pachyproctus and M.cf.pachyproctus as two groups in the following analyses and descriptions. In addition, for comparison, we also divided M.medogensis specimens into two groups, i.e., high-elevation group (above ca. 2100 m a.s.l.) and low-middle-elevation group (500\u20131600 m). The high-elevation group contained five tadpoles collected from 80k and Gedang village, and the low-middle-elevation group contained five adult males, six adult females, and four tadpoles from the urban area of Medog town, Bari village, Beibeng village, Gelin village and Didong village . The Animal Care and Use Committee of Chengdu Institute of Biology, CAS provided full approval for this research (Number: CIB2016012301). Field work was approved by the Management Office of the Administration of Yarlung Zangbo Grand Canyon National Nature Reserve (YLZB000342).In the field, after taking photographs, the toads and tadpoles were euthanized using isoflurane, and then the specimens were fixed in 75% ethanol. Tissue samples were taken and preserved separately in 95% ethanol prior to fixation. Specimens collected in this work were deposited in Total genomic DNA was extracted from each specimen collected in this study using QIAamp DNA Mini Kit , following manufacturer instructions. Three mitochondrial genes and two nuclear protein-coding genes (RAG1 and CXCR-4) were amplified and sequenced. Primer sequences were retrieved from literatures for 12S , 16S Si, COI Ch, RAG1 M, and CXCMegophrys species were downloaded from GenBank especially for their holotypes and/or topotypes for which comparable sequences were available and Bayesian Inference (BI) methods, implemented in PhyML v. 3.0 (BIC) using jModelTest v. 2.1.3 were measured ;EN eye-nostril length (distance from front of eye to the center of nostril);FAL forearm length (distance from elbow to wrist);FIIIW finger III width (largest width of tip of finger III);FIVW finger IV width (largest width of tip of finger IV);FOL foot length ;HAL hand length (distance from wrist to tip of third digit);HL head length (distance from the rear of the mandible to the tip of the snout);HLL hindlimb length;HW head width (distance between the posterior angles of jaw);IBE internal back of eyes (the shortest distance between the posterior borders of the orbits);IFE internal front of eyes (shortest distance between the anterior borders of orbits);IMT ength of the inner metatarsal tubercle;IN internarial distance (shortest distance between two nostrils);IUE inter upper eyelid width (shortest distance between upper eyelids);SHL shank length (distance from knee to ankle);SL snout length (distance from tip of snout to anterior border of the orbit);SN nostril-snout length (distance from center of the nostril to tip of the snout);SVL snout-vent length (distance from the tip of the snout to the posterior edge of the vent);TFOL tarsal-foot length (distance from heel to the tip of the fourth digit);TL thigh length (distance from cloaca to knee);TYD largest tympanum diameter;TYE tympanum-eye distance ;UEW maximum upper eyelid width.Megophrysyeae sp. nov., M.cf.pachyproctus, and two elevation groups of M.medogensis) were measured ;BW maximum body width;ED maximum eye diameter;IND internasal distance (distance between center of two naris);LF maximum height of lower tail fin;NE naris-eye distance (distance from center of naris to anterior corner of eye);ODW oral disc width ;PP interpupilar distance;RN rostro-narial distance (distance from tip of snout to center of naris);SS snout-spiracle distance (distance from tip of snout to opening of spiracle);SU snout-upper fin distance (distance from snout to beginning of upper tail fin);TAL tail length (distance between posterior side of opening of cloaca to tip of tail);TMH maximum tail muscle width;TMW maximum tail muscle height;TOL total length;UF maximum height of upper tail fin.M.vegrandis were retrieved from M.pachyproctus from SVL was calculated and then log-transformed for the following morphometric analyses. Mann-Whitney U test was used to test the significance of difference on each character between different species in each gender group. In the analyses for male group, 13 characters of 28 individuals of five species were included, and for female, 26 characters of 13 individuals of four species were included. The significance level was set at 0.05. The analyses were carried out in R of M.cf.pachyproctus, and three unvouchered males of M.medogensis with fast-Fourier transform (FFT) of 512 points, 50% overlap, and 188 Hz grid-spacing using Hanning windows. Sonograms and spectrograms were presented in figures using Praat of ng Praat after deSkull scanning. The holotype CIB201706MT02 of Megophrysyeae sp. nov., holotype CIBMT171053 of Megophryszhoui sp. nov., and the adult male CIB022017061805 of M.cf.pachyproctus were scanned. For comparisons, the holotype NWIPB 770650 of M.pachyproctus and the adult male topotype CIB022017061406 of M.medogensis were also scanned. In the high-resolution X-ray scanner , the specimens were scanned along the coronal axis at an image resolution of 1024\u00d7 1024 pixels. Segmentation and three-dimensional reconstruction of the CT images were made using VG57 Studio Max 2.2 . Terminology of skull description follows Fei and Yei (2016).ML and BI analyses based on the mitochondrial DNA matrix resulted in essentially consistent topologies ), but in nuclear DNA trees, as ). This clade with the four species was phylogenetically far from the clade containing all samples of M.medogensis in all trees. As note, in nuclear DNA trees, M.medogensis was resolved as a monophyletic group because the high-elevation and low-middle-elevation groups of M.medogensis were nested into one clade, but in mitochondrial DNA trees, the low-middle-elevation group of M.medogensis was clustered as a clade sister to M.robusta, being paraphyly with the clade in comprising of the high-elevation group of M.medogensis.All samples of Megophrys , and that between Megophrysyeae sp. nov. and other congeners was at least 5.4% (Megophrysyeae sp. nov. vs. M.vegrandis). As note, genetic distance between the low-middle-elevation and high-elevation groups of M.medogensis was 5.0% on 16S gene. These values were much higher than interspecific genetic distance between many pairs of Megophrys species than the former two species , Xizang, China; altitude 1530 m, China. Huang, 1981Holotype: adult male NWIPB 770650.SVL 35.7; a large swollen arc-shaped protuberance present on vent beyond cloaca and visible on both dorsal and lateral view, its length 6.8 , width 4.7, and thickness 2.7.; snout blunt in dorsal view, obtusely protruding beyond mandible in lateral view; rostral appendage absent; canthus rostralis well developed, loreal region concave; dorsal surface of snout slightly concave; nostril oval, slightly closer to snout than eye (EN/SN 1.04); eyes lager than twice tympanum (EL/TYD 2.24); eye-tympanum distance smaller than tympanum diameter (TYE/TYD 0.86); tympanum oval, obliquely orientated, upper 1/3 concealed with supratympanic ridge; interorbital space flat, wider than upper eyelids (UEW/IUE 0.89); pineal ocellus not visible; vomerine ridges well developed, acutely angled, enlarged at ends where bearing several vomerine teeth; maxillary teeth present; tongue notched posteriorly, medial lingual process absent.Head wider than long (FIIIW 0.8), without pads.Forearm moderately long and wide; fingers long and thin, without webbing and lateral fringes; subarticular tubercles absent; inner and outer metacarpal tubercles small and oval, weakly connected at lower half; finger relative lengths I < II < IV < III; base of finger I strong, larger than base of finger II; tips of fingers slightly swollen and rounded and rounded, close to axilla on chest; femoral glands small (diameter 1.0) and rounded, closer to outer edge of knee than to cloaca.Fig. . Dorsal According to Fig. . DescripSee for morphometric variation within the three types in Suppl. material Male with gray nuptial pad on inner side of the first finger, spines on nuptial pad dense and small; single subgular vocal sac; vocal sac opening small, slit like; a distinct fatty swollen rounded projection present on the end of body beyond cloaca.According to Megophryspachyproctus differs from all other known congeners except M.koui and M.caudoprocta by having a distinct protuberance above vent, and further differs from the latter two species in protuberance above vent being swollen and arc-shaped (vs. not). For comparisons with subsequent undescribed species covered in this paper, refer to relevant morphological comparison sections for those species.Megophryspachyproctus was originally described by M.pachyproctus does not have these character), and not having a distinct swollen arc-shaped protuberance present above vent (while the holotype of M.pachyproctus possess). M.pachyproctus. The body length of these specimens ranges from 26.1 mm to 27.9 mm, and M.pachyproctus as 25.3 mm to 36.2 mm, which should be 35.3 mm to 36.2 mm (Megophrysyeae sp. nov. (see description of Megophrysyeae sp. nov.). We suggest reexamination of these specimens should be taken. M.pachyproctus from Southern Xizang , provided description, measurements (body length 37.8), and a photo of dorsal view of the single male voucher specimen V/A/NERC/1352. But the photo does not present an arc-shaped swelling above vent Five adult females and six adult males from Medog , male 65.3 mm . Males with brown nuptial pads on fingers I and II, spines on nuptial pad dense; single subgular vocal sac.M.medogensis, description was based on tadpole CIBMT20170621 (stage 35) which shared the same pond of sequenced tadpole CIBMT022017061808 in Bari village. They are similar on morphology. For coloration at stage 26, description based on sequenced specimen CIBMT1710101 from Yadong village. Measurements in mm. For stage 35, body 13.3, elongated; head slightly narrower than trunk, oral disk large, funnel like, 1.2\u00d7 body width; three rows of short oval submarginal papillae on lower lip; middle of lower lip protruding forward, with five rounded papillae longitudinal arranged from the tip middle lower lip to oral cavity; corner of mouth with six papillae arranged in a transverse row on both sides; three transverse rows of short oval papillae on upper lip; keratodonts absent; nares closer to eyes than tip of snout (RN/NE 1.6); eyes round, positioned dorsolaterally; internarial distance (IND 3.0) 61% of the interpupilar distance (PP 4.9); spiracle mostly in left side of body, in right-handed helix from ventral view; spiracular tube not protruding beyond body wall, positioned 60% of the distance between tip of the snout and trunk-tail junction, and below the horizontal mid trunk line; tail accounts 69% of total length; dorsal fin arise above trunk-tail junction, 35% of maximum body height; ventral fin connected to the trunk, with lesser height, 27% of maximum body height; anal siphon opens medially; maximum tail muscle height 72% of maximum body height, maximum tail muscle strong, width 53% of maximum body width; 12 small curves present on both lateral side of tail muscle. For stage 26, dorsal fin arises behind trunk-tail junction. For stage 43, clear \u201cX\u201d and \u201cl_l\u201d skin ridges have present on dorsum, limbs are well developed. For high-elevation tadpoles of M.medogensis, description mostly based on sequenced tadpole CIBMT171001 (at stage 27), coloration based on sequenced tadpoles CIBMT1710106 and CIBMT1710112, collected from Gedang, Medog, Tibet Autonomous Region, China . Body 9.5, elongated; head slightly narrower than trunk; oral disk moderate, funnel like, positioned anterior-dorsal, width equal with body width; 5 transverse rows of short oval papillae on upper lip; keratodonts absent; nares much closer to eyes than tip of snout (RN/NE 2.2); eyes round, positioned dorsolaterally; internarial distance (IND1.9) 61% of the interpupil distance (PP 3.2); spiracle barely visible from ventral view; the spiracular tube not protruding beyond body wall, positioned 63% of the distance between tip of the snout and trunk-tail junction, and below the horizontal mid trunk line; tail accounts 72% of total length; dorsal fin arise above anal siphon opens, 40% of maximum body height; ventral fin connected to the trunk, with lesser height than dorsal fin, 37% of maximum body height; anal siphon opens medially; tail muscle relatively weak, maximum height 72% of maximum body height, width only 44% of maximum body width; eleven small curves present on both lateral side of tail muscle., absence of large protuberance above vent (vs. present in the latter), skin relatively smooth (vs. rough in the latter), frontoparietal distinctly wider in front than rear , sagittal suture occlusive (vs. distinctly open in the latter), and columella auris long (vs. short in the latter). For comparisons with species studied in this paper, refer to relevant morphological comparison sections for those species.Refer to Taxon classificationAnimaliaAnuraMegophryidae636D8655-349B-50B5-B431-68A80A619A2EMegophryscf.pachyproctus*** Huang, 198129.32947\u00b0N, 95.36016\u00b0E, 1780 m) by SC Shi and L Ding, on 18 June 2017. One adult male (CIBMT171056), four adult females in gravidity , and one male toadlet (CIBMT171059) were collected from vicinity of Renqingbeng Temple by SC Shi on 26 October 2017.Four adult males, CIB022017061805 Figs , 7, CIB2SVL 34.8); protuberance beyond cloaca small, barely visible from ventral view, not swollen.Adult male, CIB022017061805 Figs , 7. MeasHW 12.3, HL 11.0, IFE 6.5, IBE 10.4); snout rounded in dorsal view, slightly projecting in profile, protruding beyond lower jaw; rostral appendage absent (SL 4.6); canthus rostralis blunt; loreal region concave, dorsal surface of snout slightly concave; nostril oval, nearly in the middle of distance from snout to eye , distance between nostrils almost equal to distance between upper eyelids ; tympanum smaller than half of eyes ; eye-tympanum distance subequal to tympanum diameter (TYE 1.7); tympanum irregular rounded, upper 1/3 conceal with supratympanic ridge; interorbital space flat, larger than upper eyelid (UEW 3.2); pineal ocellus not visible; vomerine ridges distinct, orientation of two ridges acutely angled, enlarged at ends where bearing several vomerine teeth; maxillary teeth present; tongue notched posteriorly, medial lingual process absent.Head moderately large, wider than long ; fingers long and thin, with rudimentary webbing; narrow lateral fringes present on finger III, indistinct on other fingers; subarticular tubercles absent; inner and outer metacarpal tubercles mostly fused, large, with the size of base of finger I; finger length formula I < II < IV < III; base of finger I strong, larger than base of finger II; tips of fingers slightly swollen, without pads (FIIIW 1.1).Forearm moderately long and wide, similar size of upper arms, shorter than hand ; toes long and thin, relative lengths I < II < V < III < IV, rudimentary webbed, with narrow lateral fringes, tips rounded, dermal ridges continuously present on ventral surface; subarticular tubercles absent; outer metatarsal tubercle tiny and rounded; inner metatarsal tubercle distinct (IMT 1.6), nearly oval, partially fused with toe I.Hindlimbs thin and long; tibio-tarsal articulation reaches middle eye; thighs shorter than shanks but longer than feet ; eyes round, positioned dorsolaterally; internarial distance (IND1.4) 85% of the interpupil distance (PP 1.63); spiracle mostly in left side of body, in right-handed helix from ventral view, the spiracular tube not protruding beyond body wall, positioned 63% of the distance between tip of the snout and trunk-tail junction, and below the horizontal mid trunk line; tail accounts 68% of total length; dorsal fin arise above trunk-tail junction, 38% of maximum body height; ventral fin connected to the trunk, with lesser height than dorsal fin, 31% of maximum body height; anal siphon opens medially; maximum tail muscle height 72% of maximum body height, maximum tail muscle width 53% of maximum body width; eleven small curves present on both lateral side of tail muscle., M.caudoprocta ; M.hoanglienensis , M.jingdongensis , M.liboensis , M.omeimontis , M.aceras ; M.ancrae , M.damrei , M.flavipunctata , M.glandulosa , M.himalayana , M.lekaguli , M.major , M.mangshanensis , M.maosonensis , M.megacephala , M.monticola , M.periosa , M.robusta , M.longipes , M.oreocrypta , M.serchhipii , and M.takensis .By having relative smaller body size , Megophryscf.pachyproctus differs from M.zunhebotoensis , M.rubrimera , and M.angka .By having relative larger body size , Megophryscf.pachyproctus differs from M.gigantica, M.nankiangensis, and M.shapingensis .By tympanum present distinctly, Megophryscf.pachyproctus differs from M.wawuensis (vs. absent in the latter).By vomerine ridge and teeth present, Megophryscf.pachyproctus differs from M.elfina, M.gerti, M.hansi, M.koui, M.microstoma, and M.synoria (vs. absent in the latter).By maxillary teeth present, Megophryscf.pachyproctus differs from M.carinense, M.chuannanensis, M.feae, M.intermedia, and M.popei (vs. hind limbs short and head flat wide in the latter).By hind limbs long and head not wide and flat, Megophryscf.pachyproctus differs from M.lancip, M.montana, M.parallela, M.baluensis, M.edwardinae, M.kobayashii, M.ligayae, M.nasuta, and M.kalimantanensis (vs. present in the latter).By lacking a single, wide and flat palpebral projection on the edge of the upper eyelid, Megophryscf.pachyproctus differs from M.stejnegeri .By lacking rostral appendage, Megophryscf.pachyproctus differs from M.dringi (vs. present in the latter).By lacking a distinct horn-like tubercle at edge of upper eyelid, Megophryscf.pachyproctus differ from M.vegrandis, M.baolongensis, M.binchuanensis, M.binlingensis, M.boettgeri, M.brachykolos, M.cheni, M.kuatunensis, M.lini, M.lishuiensis, M.minor, M.obesa, M.palpebralespinosa, M.sangzhiensis, M.shuichengensis, M.spinata, M.tuberogranulata, M.wuliangshanensis, M.wushanensis, M.ombrophila, M.leishanensis, M.wugongensis, M.mufumontana, M.feii, M.auralensis, and M.huangshanensis, M.angka, M.shunhuangensis, M.jiangi, and M.xianjuensis (vs. absent in the latter).By vomerine teeth present, Megophryscf.pachyproctus differs from M.nanlingensis .By relatively finger lengths I < II < IV < III and nuptial pads present only on finger I, Megophryscf.pachyproctus differs from M.serchhipii (vs. at least one fourth webbed in the latter).By toes with rudimentary webbing, Megophryscf.pachyproctus differs from M.binchuanensis, M.cheni, M.jingdongensis, M.lini, M.rubrimera, M.shuichengensis, M.spinata, M.feii, M.vegrandis, and M.glandulosa (vs. wide in the latter).By toes with narrow lateral fringes, Megophryscf.pachyproctus differs from the following species: M.vegrandis (vs. smooth); M.medogensis ; M.daweimontis (vs. smooth); M.fansipanensis ; M.oropedion ; M.parva (vs. smooth); M.zhangi (vs. smooth); and M.jiulianensis .By dorsal skin rough but without spines, Megophryscf.pachyproctus differs from M.dongguanensis .By snout rounded in dorsal view and nuptial pad only present only on finger I, Megophryscf.pachyproctus further differs from M.medogensis by the following characters: nuptial pads only present on finger I in males (vs. on the first two fingers in the latter); dorsal skin rough (vs. relatively smooth in the latter); vomerine ridge moderate, vomerine teeth weak (vs. both strong in the latter).Megophryscf.pachyproctus differs from M.medogensis: skull weakly ossified, opening of anterior fontanelle present, sagittal suture distinctly open ; frontoparietal front equals rear (vs. distinctly wider in the latter); sphenethmoid rough with curves and pits, middle front edge protruding ; exoccipitals posterior to the line connecting conjunctions of quadratojugal and mandible (vs. anterior in the latter); and columella auris short (vs. long in the latter).By having following characters of skull, Megophryscf.pachyproctus differs from M.medogensis ; inner metatarsal tubercle distinct partially fused with toe I . Megophryscf.pachyproctus further differs from M.pachyproctus by having the following characters on skull morphology: premaxillary and maxillary teeth weak, separated from others by gaps ; inner edge of nasal bones half contact with sphenethmoid (vs. mostly in the latter); sphenethmoid rough with curves and pits, middle front edge protruding ; and conjunction of parasphenoid anterior process meet with sphenethmoid narrow, width ca. half the constriction near its base .Elatostema species and ferns near small mountain streams. Distribution elevation overlap with M.medogensis at 1560 m, where a small stream pond was found to have tadpoles of three Megophrys species on 18 June, including M.medogensis (at stage 42), Megophryscf.pachyproctus (at stages 26\u201327), and Megophrysyeae sp. nov. (at stages 28\u201335). Theloderma sp. and Amolopsmedogensis Li and Rao, 2005 were recorded at the same habitat.This group is currently known at elevation from 1560 m to 2003 m in Medog County, Tibet Autonomous Region, China. It inhabits mountain streams of subtropical forests. During June, males call on branches and leaves of bushes near mountain stream with a distance at least three meters from others, where covered with dense broad leaf forests by SC Shi on 26 October 2017.Figs , 8. Adul, Zhou Shi Jiao Chan .Megophryszhoui sp. nov. is assigned to the genus Megophryssensu lato based upon molecular phylogenetic analyses and the following morphological characters: canthus rostralis well-developed; supratympanic fold distinct; axillary glands small and tit-like, on sides of the breast; head length more than 25% of body size; upper jaw protruding beyond the margin of the lower jaw; no skin fold on back of head; maxillary teeth present; tympanum distinct; hind legs long and thin.Megophryszhoui sp. nov. is distinguished from its congeners by a combination of following characters: body small ; vomerine ridge weak, vomerine teeth absent; tympanum present, moderate; base of finger I in similar size with finger II, relative finger lengths I < II < IV < III, fingertips not expanded into small pads; toes with narrow lateral fringes or absent; inner metatarsal tubercle long oval, positioned on base of toe I; dorsal skin relatively smooth; protuberance beyond cloaca indistinct, barely visible from ventral view, not swollen; skull weakly ossified, premaxillary and maxillary teeth weak; skull wider slightly than long; nasal bones not contact with sphenethmoid.SVL 23.0); protuberance beyond cloaca small, not visible from ventral view, not swollen.Figs , 8. MeasHW 7.8, HL 8.3, IFE 4.5, IBE 7.2); snout near rounded in dorsal view, slightly protruding beyond lower jaw; rostral appendage absent (SL 3.6); canthus rostralis blunt; loreal region slightly concave, dorsal surface of snout slightly concave; nostril oval, closer to eye than tip of snout ; distance between nostrils approximate distance between upper eyelids ; eyes twice size of tympanum ; pupils diamond, inferior angle slightly concave; eye-tympanum distance subequal with tympanum diameter (TYE 1.1); tympanum rounded, upper 1/3 conceal with supratympanic ridge; interorbital space flat, wider than upper eyelids (UEW 2.3); pineal ocellus not visible; two arcuate vomerine ridges present, orientation of two ridges acutely angled, not enlarged at posterior ends, shortest distance between two ridges equal to length of vomerine ridges; vomerine teeth absent; maxillary teeth present; tongue weakly notched behind, medial lingual process absent.Head moderate, longer than wide ; fingers thin, without rudimentary webbing; subarticular tubercles absent; inner and outer metacarpal tubercles indistinct; base of finger I equal wide with base of finger II; finger relative length I < II < IV < III; tips of fingers slightly swollen, without pads (FIIIW 0.5).Forearm slender, not wider than upper arms, shorter than hand ; toes slender, relative length I < II < V < III < IV, rudimentary webbed, without lateral fringes, tips slightly swollen, no dermal ridges on ventral surface; subarticular tubercles absent; outer metatarsal tubercle absent; inner metatarsal tubercle long oval (IMT 1.1), positioned on base of toe I.Hindlimbs thin and long, tibio-tarsal articulation reaches middle eye; thighs shorter than shanks but longer than feet , Megophryscf.pachyproctus , M.medogensis , M.acuta , M.baolongensis , M.binchuanensis , M.binlingensis , M.boettgeri , M.brachykolos , M.caudoprocta , M.cheni , M.daweimontis , M.fansipanensis , M.hoanglienensis , M.insularis , M.jingdongensis , M.jinggangensis , M.kuatunensis , M.liboensis , M.lini , M.lishuiensis , M.minor , M.obesa , M.omeimontis , M.palpebralespinosa , M.rubrimera , M.sangzhiensis , M.shuichengensis , M.spinata , M.tuberogranulata , M.wuliangshanensis , M.wushanensis , M.ombrophila , M.leishanensis , M.dongguanensis , M.nankunensis , M.jiulianensis , M.nanlingensis , M.wugongensis , M.mufumontana , M.feii , M.vegrandis , M.aceras ; M.ancrae , M.auralensis , M.damrei , M.flavipunctata , M.glandulosa , M.himalayana , M.huangshanensis , M.katabhako , M.lekaguli , M.longipes , M.major , M.mangshanensis , M.maosonensis , M.megacephala , M.monticola , M.periosa , M.robusta , M.longipes , M.oreocrypta , M.oropedion , M.parva , M.periosa , M.robusta , M.sanu , M.serchhipii , M.takensis , M.zhangi , M.zunhebotoensis , M.angka , M.shunhuangensis , M.jiangi , and M.xianjuensis .By body relatively smaller , Megophryszhoui sp. nov. differs from M.gigantica, M.nankiangensis, M.shapingensis, and M.wawuensis .By tympanum distinct moderate, larger than half eye diameter, Megophryszhoui sp. nov. differs from M.elfina, M.gerti, M.hansi, M.koui, M.microstoma, and M.synoria (vs. absent in the latter).By maxillary teeth present, Megophryszhoui sp. nov. differs from M.carinense, M.chuannanensis, M.feae, M.intermedia, and M.popei (vs. head wide flat and hind limbs short in the latter).By hind limbs long and head not wide and flat, Megophryszhoui sp. nov. differs from M.lancip, M.montana, M.parallela, M.baluensis, M.edwardinae, M.kobayashii, M.ligayae, M.nasuta, and M.kalimantanensis (vs. present in the latter).By lacking a single, wide and flat palpebral projection on the edge of the upper eyelid, Megophryszhoui sp. nov. differs from M.stejnegeri .By lacking rostral appendage, Megophryszhoui sp. nov. differs from M.dringi (vs. present in the latter).By lacking a distinct horn-like tubercle at edge of upper eyelid, Megophryszhoui sp. nov. differs from M.pachyproctus, M.medogensis, and Megophryscf.pachyproctus (vs. vomerine ridge stronger in the latter); differs from M.vegrandis, M.baolongensis, M.binchuanensis, M.boettgeri, M.kuatunensis, M.lishuiensis, M.wuliangshanensis, M.wushanensis, M.ombrophila, M.leishanensis, M.feii, M.huangshanensis, M.shunhuangensis, and M.jiangi (vs. absent in the latter).By vomerine ridge weak, Megophryszhoui sp. nov. differs from Megophryscf.pachyproctus, M.pachyproctus, M.medogensis, M.caudoprocta, M.daweimontis, M.fansipanensis, M.hoanglienensis, M.insularis, M.jingdongensis, M.jinggangensis, M.liboensis, M.omeimontis, M.rubrimera, M.dongguanensis, M.nankunensis, M.jiulianensis, M.nanlingensis, M.aceras, M.ancrae, M.damrei, M.flavipunctata, M.glandulosa, M.himalayana, M.katabhako, M.lekaguli, M.longipes, M.major, M.mangshanensis, M.maosonensis, M.megacephala, M.monticola, M.oreocrypta, M.oropedion, M.parva, M.periosa, M.serchhipii, M.takensis, M.zhangi, and M.zunhebotoensis (vs. present in the latter).By vomerine teeth absent, Megophryszhoui sp. nov. differs from M.binchuanensis, M.cheni, M.jingdongensis, M.lini, M.rubrimera, M.shuichengensis, M.spinata, M.feii, M.vegrandis, and M.glandulosa (vs. wide in the latter).By toes with narrow lateral fringes or absent, Megophryszhoui sp. nov. differs from M.pachyproctus, Megophryscf.pachyproctus, M.insularis, M.jinggangensis, M.tuberogranulata, M.wuliangshanensis, M.leishanensis, M.dongguanensis, M.jiulianensis, M.nanlingensis, M.wugongensis, M.mufumontana, and M.feii (vs. rough in the latter).By dorsal skin relatively smooth, TYD/EL 0.40\u20130.60, n = 9), Megophryszhoui sp. nov. differs from species with large tympanum: M.brachykolos ; M.jinggangensis , and M.takensis .By tympanum moderate .By fingertips not expanded into small pads, Megophryszhoui sp. nov. differs from M.pachyproctus: protuberance beyond cloaca small, not visible from ventral view, not swollen ; and inner metatarsal tubercle long oval, positioned on base of toe I .By the following characters, Megophryszhoui sp. nov. differs from M.pachyproctus: premaxillary and maxillary teeth weak, barely visible or separated from others by gaps ; nasal bones not contact with sphenethmoid (vs. mostly in the latter); and middle front edge of sphenethmoid protruding (vs. truncate in the latter).By having following differences on skull morphology, Megophryszhoui sp. nov. differs from M.medogensis .By base of finger I in similar size with finger II, relative finger lengths I < II < IV < III, Megophryszhoui sp. nov. differs from M.medogensis: skull weakly ossified, opening of anterior fontanelle present, sagittal suture narrowly or wide open ; premaxillary and maxillary teeth weak, barely visible or separated from others by gaps ; frontoparietal front equals rear (vs. distinctly wider in the latter); exoccipitals posterior to the line connecting conjunctions of quadratojugal and mandible (vs. anterior); and columella auris short (vs. long in the latter).By having following differences on skull, Megophryszhoui sp. nov. differs from Megophryscf.pachyproctus .By base of finger I similar in size with finger II, nasal bones not in contact with sphenethmoid, and texture of sphenethmoid relatively smooth with several small pits, Taxon classificationAnimaliaAnuraMegophryidaeA1D67614-55C0-5A09-A338-9B41D1E1934Fhttp://zoobank.org/983FA221-7721-49AE-B8F7-568383A19D1829.24292\u00b0N, 95.18561\u00b0E, 870 m), at 1:40 h on 15 June 2017 by SC Shi and L Ding.Figs , 9. CIB229.22508\u00b0N, 95.12463\u00b0E, 670 m) on 11 June 2017 by SC Shi and L Ding. One adult female (CIB201706MT03) collected on 13 June 2017 in Medog urban neighborhood by SC Shi and L Ding. One adult female (CIBMTXC-201701-043) and one adult male (CIBMTXC-201701-044) collected on 28 May 2017 in Medog City neighborhood by F Xie and DW Yang. Two adult males (CIB022017061606 and CIB022017061407) collected in the same location of holotype by SC Shi and L Ding. One male (CIB022017061804) collected in Bari village at 21:01 18 June 2017 by S.C. Shi. Two adult males (CIBMT171065 and CIBMT171066) collected on 10 and 24 October 2017 in Yarang village by F Xie and DW Yang. One adult male (CIBMT171064) collected at 23:54, 25 October 2017 in Yadong village in the vicinity of Medog city suburb by SC Shi and B Wang.Thirteen specimens from Medog County, Tibet Autonomous Region, China. Four adult males collected in Didong village , Ye Shi Jiao Chan .Megophrysyeae sp. nov. is assigned to the genus Megophryssensu lato based on molecular phylogenetic analyses and the following morphological characters: canthus rostralis well-developed; a tiny horn\u2019-like tubercle at edge of upper eyelid present; supratympanic fold distinct; axillary glands small and tit-like, on sides of the breast; oral disc of tadpoles funnel-like; mouth of tadpoles lacking transverse rows of teeth; head length more than 25% of body size; upper jaw protruding beyond the margin of the lower jaw; no skin fold on back of head; maxillary teeth present; tympanum distinct; hind legs long and thin.Megophrysyeae sp. nov. is distinguished from its congeners by a combination of following characters: body relatively small ; vomerine ridge weak, vomerine teeth absent; base of first finger weak, size equal to the base of second finger, tips of fingers II-IV flat, expand to small pad; foot of males shorter ; dorsal skin being relatively smooth; protuberance beyond cloaca small, not visible from ventral view, not swollen; nuptial pad absent; skull weakly ossified, wider than long; premaxillary and maxillary teeth weak, separated from others by gaps; texture of sphenethmoid smooth, without curves and pits; anterior fontanelle opening large, sagittal suture occlusive; advertisement call short and fast , and dominant frequency high .SVL 27.5); protuberance beyond cloaca small, not visible from ventral view, not swollen.Figs , 9. MeasHW 9.8, HL 9.0, IFE 5.1, IBE 8.7); snout rounded in dorsal view, slightly projecting in profile, protruding beyond lower jaw, rostral appendage absent (SL 3.6); loreal region vertical and concave; canthus rostralis blunt; dorsal surface of snout slight concave; nostrils oval, nearly in the middle of distance from snout to eye; distance between nostrils (IN 3.2) almost equal with the shortest distance between upper eyelids (IUE 3.1); tympanum small, rounded, diameter (TYD 1.6) less than half of eye length (EL 3.8 mm), upper one third of tympanum anulus merge with supratympanic fold equal to tympanum diameter; pupil near oval, with a gap at lower edge; visible pineal ocellus absent; vomerine ridges weak, interval longer than its length, vomerine teeth absent; tongue feebly notched behind, hardly visible, with no medial lingual process.Head moderate, wider slightly than long 25% of body length, slightly shorter than hand (HAL 8.3), not enlarged relative to the upper arm; relative finger lengths I < II < IV < III; base of first finger weak, size equal to the base of second finger; tips of finger I rounded, slightly swollen, tips of fingers II-IV flat and expanded, forming small oval pads , pads without grooves and distinctively larger than terminal phalanges; fingers rudimentary webbed, with ventral callous ridges and narrow lateral fringes; subarticular and supernumerary tubercles absent, palmar tubercles indistinct.Forearm long and slim, forearm length (SHL 14.1) slightly longer than thigh (TL 12.3) and feet ; toes thin, rudimentary webbed, with ventral callous ridges and narrow fringes; relatively toes lengths I < II < V < III < IV; tips of toes flat and slightly dilated, without grooves, slightly larger than terminal phalanges; inner metatarsal tubercle weak (IMT 1.9) and elliptical, outer metatarsal tubercle, subarticular and supernumerary tubercles absent.Hindlimbs long and thin, tibio-tarsal articulation reaches area between nostril and eye; heels meet when thighs are positioned at right angles to the body, shank . Calls frequent, average calls per seconds 3.0, vary from 1.9 to 4.1; average intercall interval 218 ms, vary from 649 ms to 119 ms when ambient temperatures vary from 17 \u00b0C to 25 \u00b0C. The number of calls in each call group average 68.9, range from 5 to 187. Calls short, duration average 139 ms, range from 89 ms to 246 ms. Pules per call average 9.2, vary from 7 to 12. To human ears, sound like cricket.; internarial distance average 69% (64\u201378%) of the interorbital distance; eyes positioned dorsolaterally, the pupils rounded; spiracle in right-handed helix from ventral view, spiracular tube not protruding beyond body wall, positioned 53% (47\u201357%) of the distance between tip of the snout and trunk-tail junction, and opens laterally; the tail makes up average 69% (67\u201372%) of the total body length; dorsal fin arise behind trunk-tail junction, average 35% (30\u201341%) of maximum body height; the basal tail width average 60% (48\u201365%) of the maximal trunk width; keratodonts absent. were calling in the same stream where one male (CIB022017061804) of the new species was calling together at nearest distance ca. 3 meters in Bari Village . From its habitat, other amphibians like Megophrysmedogensis, Megophryscf.pachyproctus, Odorranazhaoi Li, Lu, and Rao, 2008, Amolopsmedogensis, and Huangixalustranslineatus Wu, 1977 were also recorded.This species is currently known from five localities in Medog County, Tibet Autonomous Region, China Fig. . All calMegophrysyeae sp. nov. differs from M.pachyproctus , Megophryscf.pachyproctus , M.medogensis , M.baolongensis , M.binchuanensis , M.binlingensis , M.boettgeri , M.brachykolos , M.caudoprocta , M.daweimontis , M.fansipanensis , M.hoanglienensis , M.insularis , M.jingdongensis , M.jinggangensis , M.liboensis , M.lini , M.lishuiensis , M.minor , M.obesa , M.omeimontis , M.palpebralespinosa , M.sangzhiensis , M.shuichengensis , M.spinata , M.tuberogranulata , M.wushanensis , M.leishanensis , M.dongguanensis , M.nankunensis , M.jiulianensis , M.nanlingensis , M.wugongensis , M.mufumontana , M.aceras ; M.ancrae , M.auralensis , M.damrei , M.flavipunctata , M.glandulosa , M.himalayana , M.huangshanensis , M.katabhako , M.lekaguli , M.longipes , M.major , M.mangshanensis , M.maosonensis , M.megacephala , M.monticola , M.periosa , M.robusta , M.longipes , M.oreocrypta , M.oropedion , M.parva , M.periosa , M.robusta , M.sanu , M.serchhipii , M.takensis , M.zhangi , M.zunhebotoensis , M.angka , M.shunhuangensis , M.jiangi , and M.xianjuensis .By body relatively smaller , Megophrysyeae sp. nov. differs from M.gigantica, M.nankiangensis, M.shapingensis, and M.wawuensis .By tympanum distinct moderate, Megophrysyeae sp. nov. differs from M.elfina, M.gerti, M.hansi, M.koui, M.microstoma, and M.synoria (vs. absent in the latter).By maxillary teeth present, Megophrysyeae sp. nov. differs from M.carinense, M.chuannanensis, M.feae, M.intermedia, and M.popei (vs. head wide flat and hind limbs short in the latter).By hind limbs long and head not wide and flat, Megophrysyeae sp. nov. differs from M.lancip, M.montana, M.parallela, M.baluensis, M.edwardinae, M.kobayashii, M.ligayae, M.nasuta, and M.kalimantanensis (vs. present in the latter).By lacking a single, wide and flat palpebral projection on the edge of the upper eyelid, Megophrysyeae sp. nov. differs from M.stejnegeri .By lacking rostral appendage, Megophrysyeae sp. nov. differs from M.dringi (vs. present in the latter).By lacking a distinct horn-like tubercle at edge of upper eyelid, Megophrysyeae sp. nov. differs from M.pachyproctus, M.medogensis, and Megophryscf.pachyproctus (vs. stronger in the latter); differs from M.vegrandis, M.baolongensis, M.binchuanensis, M.boettgeri, M.kuatunensis, M.lishuiensis, M.wuliangshanensis, M.wushanensis, M.ombrophila, M.leishanensis, M.feii, M.huangshanensis, M.shunhuangensis, M.jiangi, and M.xianjuensis (vs. absent in the latter).By vomerine ridge weak, Megophrysyeae sp. nov. differs from Megophryscf.pachyproctus, M.pachyproctus, M.medogensis, M.caudoprocta, M.daweimontis, M.fansipanensis, M.hoanglienensis, M.insularis, M.jingdongensis, M.jinggangensis, M.liboensis, M.omeimontis, M.rubrimera, M.dongguanensis, M.nankunensis, M.jiulianensis, M.nanlingensis, M.aceras, M.ancrae, M.damrei, M.flavipunctata, M.glandulosa, M.himalayana, M.katabhako, M.lekaguli, M.longipes, M.major, M.mangshanensis, M.maosonensis, M.megacephala, M.monticola, M.oreocrypta, M.oropedion, M.parva, M.periosa, M.serchhipii, M.takensis, M.zhangi, and M.zunhebotoensis (vs. present in the latter).By vomerine teeth absent, Megophrysyeae sp. nov. differs from Megophryscf.pachyproctus, Megophryszhoui sp. nov., M.pachyproctus, M.acuta, M.binlingensis, M.brachykolos, M.cheni, M.lini, M.minor, M.obesa, M.palpebralespinosa, M.sangzhiensis, M.shuichengensis, M.spinata, M.tuberogranulata, M.wugongensis, M.mufumontana, M.auralensis, and M.robusta (vs. expanded pads on fingertips absent in the latter).By tips of fingers II-IV flat, expand to small pad, FOL 10.8\u201312.6 mm, n = 12), tympanum relatively smaller , and toes with narrow lateral fringes, Megophrysyeae sp. nov. further differs from M.vegrandis .By foot of males shorter .By dorsal skin being relatively smooth, Megophrysyeae sp. nov. differs from M.medogensis by the following characters: nuptial pad absent (vs. present in the latter); and base of first finger weak, size equal to the base of second finger, relative finger lengths I < II < IV < III .Megophrysyeae sp. nov. differs from M.medogensis: skull weakly ossified, opening of anterior fontanelle large ; premaxillary and maxillary teeth weak, separated from others by gaps ; texture of sphenethmoid smooth, without curves and pits ; frontoparietal front equals rear (vs. distinctly wider in the latter); exoccipitals posterior to the line connecting conjunctions of quadratojugal and mandible (vs. anterior); and columella auris short (vs. long in the latter).By having following differences on skull morphology, Megophrysyeae sp. nov. differs from M.medogensis: dominant frequency significantly higher ; call significantly faster ; and call intervals significantly longer .By having following differences on bioacoustics, Megophrysyeae sp. nov. differs from M.pachyproctus: lacking a swollen protruding beyond cloaca (vs. present in the latter); nuptial pad absent (vs. present in the latter); and base of first finger weak, size equal to the base of second finger .By having the following characters, Megophrysyeae sp. nov. differs from M.pachyproctus: premaxillary and maxillary teeth weak, separated from others by gaps ; texture of sphenethmoid smooth, without curves and pits ; anterior fontanelle opening large (vs. occlusive in the latter); and sagittal suture occlusive (vs. distinctly open in the latter).By having the following characters on skull morphology, Megophrysyeae sp. nov. differs from Megophryscf.pachyproctus: nuptial pad absent (vs. present on finger I in the latter); and base of first finger weak, size equal to the base of second finger .By having the following characters, Megophrysyeae sp. nov. differs from Megophryscf.pachyproctus: texture of sphenethmoid smooth, without curves and pits ; anterior fontanelle opening large ; and sagittal suture occlusive (vs. distinctly open in the latter).By having following characters on skull morphology, Megophrysyeae sp. nov. differs from Megophryscf.pachyproctus: call significantly shorter ; dominant frequency much higher ; call intervals significantly shorter ; and calls significantly faster .By having the following acoustical characters, Megophrysyeae sp. nov. differs from Megophryszhoui sp. nov.: texture of sphenethmoid smooth, without curves and pits ; and sagittal suture occlusive (vs. narrowly or wide open in the latter).By having following characters on skull morphology, Megophrys species described here. First, in this region, M.medogensis, especially its tadpoles, are almost sympatric with all other related species\u2019 tadpoles at extensive elevations even in the microhabitats, probably arousing the judgement of \u201cone population with one species\u201d. Moreover, the related species were superficially similar morphologically, easily misleading the identifications if made without detailed examination, especially for the first identification in the field. Of course, the third was insufficient expeditions. M.pachyproctus without reporting their morphological information. But in our phylogenetic trees, these two specimens were deeply nested into the Megophrysyeae sp. nov. clade , the specimens of Megophrys (Ophryophyne) from the type locality of M.koui vary in the presence of protruding vent while they share other morphological characters . Furthermore, M.pachyproctus was described based only on two males and one female. All these observations increase the uncertainty of whether the swelling protrusion can be used as a diagnostic character of M.pachyproctus. Our specimens M.cf.pachyproctus from Renqinbeng and Bari differ from the holotype of M.pachyproctus from Gelin mostly in the following characters: protuberance beyond cloaca small, barely visible from ventral view, not swollen ; and inner metatarsal tubercle distinct partially fused with toe I (vs. separate from base of toe I at a distance nearly twice its diameter in the latter). But M.cf.pachyproctus is similar to M.pachyproctus on many other morphological characters and high-elevation group (> 2100 m), because these samples phylogenetically clustered into two lineages based on mitochondrial DNA dataset but formed a single lineage when based on nuclear DNA dataset. The discordance indicates introgression between these two groups. The tadpoles of high-elevation group are morphologically different from the low-middle-elevation group: body coloration deep brown with copper pigmentation vs. body yellow-brown without copper pigmentation; tail muscle weaker (TMW/BW 44%) than the latter (TMW/BW 53\u201357%); lateral tail without dark patches vs. present. The morphological comparisons between adults of the two groups were not applicable in this work because no adults of the high-elevation groups were collected. The scenario of phylogenetical discordance between different gene datasets was also found in M.monticola (Megophrys in this region (i.e., Megophrysyeae sp. nov., Megophryszhoui sp. nov., and M.vegrandis being genetically closer; Fig. Megophryszhoui sp. nov. just lives above 2000 m near the Renqingbeng Temple in Medog County, Megophrysyeae sp. nov. has a larger range but in some other sites at elevations between 500\u20131800 m (Figs M.vegrandis has been just found at 1110 m in a southwestern locality away from the type localities of the first two relatives (Megophryscf.pachyproctus and Megophrysyeae sp. nov. in the same pond, and M.medogensis with Megophryscf.pachyproctus, Megophryszhoui sp. nov., and Megophrysyeae sp. nov. in the same stream, indicating the \u201csympatric but phylogenetically distant\u201d model. These biogeographical patterns have often been found in Megophrys (In this work, we classified samples of onticola . The mec group 68\u20131560 m agroup > 20 m, becaelatives . This caM.medogensis prefers tropical and subtropical forest floor (Fig. Megophrysyeae sp. nov. is typically found calling on the leaves of tall dense plants (Fig. Megophryscf.pachyproctus calls on the branches of bushes (Fig. Megophryscf.pachyproctus possess unique long calls, making a distinctly contrast with Megophrysyeae sp. nov. in the same stream which emit short calls (Fig. M.medogensis presents bigger body size, while the two \u201cstanding-on-plants or leaves\u201d species have a pale body. Probably for further isolations, Megophryscf.pachyproctus with relatively moderate body size prefers relative harder branches, vines, or stem of plants (Fig. Megophrysyeae sp. nov. and Megophryszhoui sp. nov. often stand on soft leaves and/or grass by their lighter body (Fig. Separations of the horned toad species in Medog are also likely reflected on their different behaviors. Although being sympatric even in the same stream at elevations between 1500\u20131800 m in Bari village (Fig. oor Fig. , while Mnts Fig. , and Meghes Fig. . It is ills Fig. ; Table 3nts Fig. , while tody Fig. , even deody Fig. . It is fThe discoveries of the new species indicate a much-underestimated biodiversity in the Himalayan Mountains. Yet, the amphibians in the region are suffering from obvious threats in their habitats, for example, the ongoing construction of roads, towns, and houses, the use of pesticide chemicals for farming, and increasing activities of tourists. And, we also still have a poor understanding of the influences of local and/or global climatic changes. Undoubtedly, it is urgent to investigate their population status for the conservation of these extraordinary toads."} +{"text": "Arbuscular mycorrhiza (AM) is an ancient mutualistic symbiosis formed by 80\u201390 % of land plant species withthe obligatorily biotrophic fungi that belong to the phylum Glomeromycota. This symbiosis is mutually beneficial, asAM fungi feed on plant photosynthesis products, in turn improving the efficiency of nutrient uptake from the environment. The garden pea (Pisum sativum L.), a widely cultivated crop and an important model for genetics, is capable offorming triple symbiotic systems consisting of the plant, AM fungi and nodule bacteria. As transcriptomic and proteomic approaches are being implemented for studying the mutualistic symbioses of pea, a need for a reference transcriptome of genes expressed under these specific conditions for increasing the resolution and the accuracy of othermethods arose. Numerous transcriptome assemblies constructed for pea did not include mycorrhizal roots, hence theaim of the study to construct a reference transcriptome assembly of pea mycorrhizal roots. The combined transcriptome of mycorrhizal roots of Pisum sativum cv. Frisson inoculated with Rhizophagus irregularis BEG144 was investigated,and for both the organisms independent transcriptomes were assembled (coverage 177x for pea and 45x for fungus).Genes specific to mycorrhizal roots were found in the assembly, their expression patterns were examined with qPCR ontwo pea cultivars, Frisson and Finale. The gene expression depended on the inoculation stage and on the pea cultivar.The investigated genes may serve as markers for early stages of inoculation in genetically diverse pea cultivars. Plants are able to establish mutualistic association with thearbuscular mycorrhizal (AM) fungi that improve the efficiencyof nutrient uptake from the environment. About 80\u201390 % ofall land plant species may form mutually beneficial symbiosiswith the obligatorily biotrophic AM fungi that belong to thephylum Glomeromycota . The AM facilitates plant nutritionand increases plant tolerance to biotic and abiotic stresses,when AM fungi feed on photosynthesis products and utilizea considerable proportion of the assimilated carbon .The garden pea (Pisum sativum L.) is a widely cultivatedcrop plant and the first model object of genetics. Similarlyto other legume plants belonging to the Fabaceae family, itis capable of forming triple symbiotic systems consistingof plant, AM fungi and nodule bacteria . The formation of symbioses increases yield and plantfitness in general , although the effect ofinoculation is often dependent on experimental conditions andplant genotype . During the last decade, transcriptomicand proteomic approaches had been implemented for studyingthe mutualistic symbioses of pea, which implied the need fora reference genomic or transcriptomic sequences required forproper annotation of transcripts/proteins under analysis. Although numerous transcriptome assemblies were constructed, no samplescontaining mycorrhizal roots had been analysed. Moreover,the only available genomic sequence isfar from ideal and lacks sequences of many important genes.Thus, the present work aimed at obtaining the referencetranscriptome assembly of pea mycorrhizal roots using RNAseq. In order to validate the constructed assembly, which isdestined for further analysis of the mycorrhization in pea withuse of transcriptomics and/or proteomics, we designed theset of primers for qPCR expression analysis and successfullyquantitated the expression level of 10 AM-specific genes inmycorrhizal roots of two pea cultivars.Plants and microorganisms used. The wild-type Pisum sativum L. cultivars Frisson )and Finale ) were used in this study.The fungal isolate Rhizophagus irregularis BEG144 wasprovided by the International Bank for the Glomeromycota as a substrate-root based inoculum for leek(Allium porrum L.) pot cultures. It was used to obtain nursepots of chives (Allium schoenoprasum L.) for the R. irregularis-inoculated pea plants )Plant growth conditions and root sampling. In order toprovide an efficient inoculation of P.sativum plants, nurse potswith established mycorrhiza were used. These were 300-mlceramic flower pots filled with opoka-rock mineral substrate,which is silica rich marl , supplementedwith 1 g .L\u20131 calcium orthophosphate. Prior to nurse pots preparation, pots with substrate were sterilized by autoclavingfor 60 min at 134 \u00b0C and 0.22 MPa. Procedures for the chivebased nurse pots are described by .Seeds of P. sativum were surface-sterilised for 10 minuteswith 98 % sulphuric acid, rinsed with sterile deionised waterfive times, and then germinated for 3 days at 27 \u00b0C in thedark on sterile vermiculite in Petri dishes with 30 ml of water added to each one. Three P. sativum seedlings of similarsize were planted into each nurse pot around a mycorrhizalchive plant. Plants were grown in a growth chamber under the following conditions:day/night, 16/8 h; temperature, 24/22 \u00b0C; relative humidity, 75; irradiation 10000 lux and were supplemented once aweek with 1/2-x Hoagland\u2019s solution without phosphate (50 mL per pot), and watered as needed.After several days of co-cultivation with chives in nursepots P.sativum root samples were collected for transcriptomeanalyses and RT-qPCR (see relevant sections) and immediatelyfrozen in liquid nitrogen and stored at \u201380 \u00b0C. Frozen rootsamples were ground in liquid nitrogen using pestle and mortar. Before collecting plant material for those analyses, severallateral roots (15 cm length) from each pea root system wererandomly selected and frozen at \u201320 \u00b0C and then subjectedto analysis of AM development as described by Shtark andcolleagues . The parameters of root colonization of these pea plants estimated according to were: M % , and a % For transcriptome sequencing root samples were collectedafter 25 days of co-cultivation with chives. Three plants ofcv. Frisson with M % = 68.6\u00b12.6, and a % = 50.9\u00b11.2 ), were chosen forthe transcriptome analysis. The whole root systems were cutoff directly below the cotyledons and frozen in liquid nitrogenin 50 mL Falcon tubes.For RT-qPCR assays root samples were collected after 7,14 or 28 days of co-cultivation with chives. Root samples ofuninoculated plants grown under the same conditions duringthe same time periods were used as a control. Lateral rootswere used, in which tips 1 cm long were removed. The collected samples were frozen in 2 mL Eppendorf\u2122 tubes. TheAM development was analysed at two time points (after 14 and28 days of co-cultivation with chives). The parameters of cv.Finale root colonization were: M % = 17.5\u00b12.3, and 35.0\u00b14.7,respectively; a % = 29.4\u00b15.7, and 36.5\u00b15.7, respectively. Thislevel of colonization is common with cv. Finale . The parameters of cv. Frissonroot colonization were: M % = 44.6\u00b14.7, and 68.1\u00b15.4, respectively; a % = 62.6\u00b13.5, and 65.3\u00b14.4, respectively. Thisis also consistent with previous investigations; in particular itwas shown that internal AM colonization and arbuscule development reaches higher values in cv. Frisson than in cv. FinaleTranscriptome sequencing. The RNA extraction, libraryconstruction and the sequencing on an Illumina 2500 HiSeqplatform was carried out by GenXPro GmbH Read preparation. In order to remove possible human andbacterial contaminants from the raw data we used the method,devised by dr. Brian Bushnell and described in removeHumantool from the BBTools suite . Additionally,reads belonging to bacteria and viruses were discarded usingthe databases provided by the author of the package. In orderto separate fungal reads from those of pea, we first preparedthe genome assembly of Rhizophagus irregularis strainDAOM197198 from as described bythe author of the bbmap package. The areas of genome, containing multiple tandem short k-mers, as well as windows oflow entropy sequences, which were calculated using pentamerfrequencies, were masked using the bbmask.sh script. In orderto exclude the sequences, common between the R. irregularisgenome and plant genomes, all the available non-draft plantgenomes from the Phytozome V12 were masked for repetitive sequences, and then used to exclude all the non-specific parts of the DAOM197198 genomeas described for the bbmask.sh script. The resulting maskedassembly was used for read mapping using the bbmap.shscript. All the mapped reads were considered to belong tothe fungus, all the non-mapped reads were considered plantreads. The transcriptome completeness and assembly qualitywere assessed using BUSCO algorithm .Blast search was used for the comparison of the varioustranscriptomes.Transcriptome assembly. The reads belonging to Pisumwere then assembled using Trinity assembler (v2.6.6) with default parameters, rnaSPAdes (v3.11.1). Corset/Lace pipeline was used toassemble the SuperTranscriptome .The transcriptome shotgun assemblies (TSAs) from thefollowing bioprojects were downloaded from the NCBI forcomparison to current assembly: PRJNA277074 \u2013 cv. Kaspa, PRJNA277076 \u2013 cv. Parafield , PRJNA308776 \u2013 cv. Torsdag . The assembly of the nodule transcriptome of cv. SGE(accession GDTM00000000.1) and the assembly of roots ofcv. SGE (accession GDTL00000000.1) were also downloadedfrom the NCBI . Additionally, the assemblies from cv. Cam\u00e9or andcv. Little Marvel were downloadedfrom supplementary files for the respective articles. The CDSsequences from the M. truncatula v4.0v2 genome were usedfor benchmarking the assembled transcriptomes .The following accessions were downloaded from the NCBIin order to identify the R. irregularis strain closest to BEG144:GCA_000439145.3, GCA_000597565.1, GCA_000597585.1,GCA_000597605.1, GCA_000597625.1, GCA_000597645.1,GCA_000597665.1, GCA_000597685.1, GCA_001593125.1,GCA_001593145.1, GCA_001593155.1, GCA_001593205.1,GCA_002897155.1, GCA_003833045.1, GCA_003833115.1.The reads binned as belonging to the fungi were assembled denovo using the Trinity assembler. Cufflinks (v2.2.1) was used to build a genome-guided assemblyAnnotation. CDS discovery for both the organisms wasperformed using the transdecoder (v5.2.0) algorithm (https://github.com/TransDecoder/TransDecoder/). Both the hmm andthe blast homology search options were used, according to the manual. The annotation was performed using the EggNOG 5.0database using the eggNOG-mapper (v2.0.1) In order to determine the best overall assembly, the threetranscriptomes were evaluated using the BUSCO tool RT-qPCR. Total RNA was isolated using the TriZol reagent. cDNA synthesis was performedwith reverse transcriptase and oligodT primers . RT-qPCRwas performed on the CFX-96 C1000 thermocycler with the double-stranded DNAdye SYBR Green . The datawas analysed using the 2-\u0394\u0394Ct method . PCR amplification was confirmed with the dissociationcurve method (55 to 95 \u00b0C). mRNA levels were normalisedin relation to the ubiquitin and actin reference genes. Threebiological replicates were analysed. The primers were constructed using the Vector NTI suite (Table 1). Theexpression levels of the genes of interest (GOI) relative to thereference genes Ubiquitin and Actin were calculated for eachcDNA sample using the CFX Manager\u2122 software version 2.1. The expression levels of GOIwere calculated as ratio of treated samples to control samples.Statistical analysis was conducted by SIGMAPLOT13 .In order to obtain a reference transcriptome of the mycorrhizalroots of P. sativum, the RNA from this tissue was sequencedon an Illumina 2500 sequencing platformA total of 120 mln pairs of reads with average length of150 bp were obtained. After quality trimming 119 mln readsremained. Since we knew, that R. irregularis transcripts arepresent in the tissues, we decided to remove all possible contaminants .Additionally, we masked low complexity regions and repetitive elements from R. irregularis genome. Of the 119 mlnremaining reads 6.7 mln (approximately 5 %) of the paired reads were mapped onto the masked Rhizophagus genome. The resulting reads belonging to P. sativum were then assembled using two assemblers: Trinity with default parametersand rnaSPAdes with default parameters. Afterwards, with useof Corset/Lace pipeline, a SuperTranscripts assembly wasconstructed using these two assemblies comprising 94360 supertranscripts (Table 2).In order to determine the best overall assembly, the three transcriptomes were evaluated using the BUSCO tool. Results ofthe analysis are presented in the Table 3.As BUSCO tends to favor the number of transcripts, theTrinity assembly scored higher than the SuperTranscriptsassembly, despite the latter containing the former. The othercomparisons, such as N50 and the duplication numbers speakin favor of the SuperTranscripts assemblyhttps://cloud.arriam.ru/s/RKD67CZak58BzzN)The resulting SuperTranscripts assembly, as well as theother two assemblies, the table of relation between the assemblies and the full results of are available at the , the results are presented inthe Table 4.Since the SuperTranscript assembly contains the twoother assemblies, it was used to compare to all available peatranscriptome assemblies. The comparison was performedusing the BLASTN algorithm . Our assembly had an almostidentical number of transcripts, homologous to those ofM. truncatula as the more diverse transcriptomes of cv. Kaspa,cv. Parafield, and cv. Cam\u00e9or, and also showed a large numberof previously undiscovered transcriptsIn order to check for possible rhizobial contamination andformation of nodules possibly missed during sample preparation we decided to search for nodule specific proteins. Sincethe expression counts for a single RNAseq analysis cannotbe considered statistically significant, we chose instead tosearch for contigs, encoding proteins, specific to nodules \u2013NCR peptides . Using the approach fromthat article, we found only 28 genes of the NCR gene familyin the newly assembled transcriptome, compared to 40 in thecv. SGE root tips and 425 in the cv. SGE nodules. Therefore,it is reasonable to assume that the plants were not accidentallyinfected with rhizobia, and thus are representative of a fungalmonoinoculation. Novel transcripts of Rhizophagus irregularishttps://www.ncbi.nlm.nih.gov/bioproject/PRJNA299202/). This genomewas used for a genome-guided Cufflinks assembly. The mapping results are presented in the Table 6.Since for now there is no published genome available for thestrain BEG144 used in this study, we decided to determinethe closest related strain in the NCBI database. To do this,we downloaded all the available R. irregularis genomes andmapped the filtered transcripts using bbmap.sh to the genomes.The best overall mapping was to the strainA1 of R. irregularisGCA_001593125.1 . The Cufflinks assembly contained 12036 (77.8 %) protein-coding genes, whereas the Trinity assembly contained17909 (63.7 %). After comparing the assemblies with theblast algorithm we discovered that 8301 (68 %) of CufflinksCDS-containing transcripts corresponded to 12036 (60.1 %)of CDS-containing transcripts of Trinity. The rest of thetranscripts, unique to the Trinity assembly may represent theparts of genome different between the strain BEG144 andthe strain used as the reference. The low coverage and theunavailability of the genome of the strain BEG144 make itharder to distinguish the real transcripts from the chimeric.The results, however, show the usability of proposed methodsto assemble the transcriptomes of mixed samples, even in theabsence of high-quality reference genomes.In order to study the inoculation effects in detail and to monitorthe AM development during the experiments, the set of markergenes with AM-specific expression pattern was required. Inprevious work by Grunwald et al. (2004), a set of 25 geneswhich were upregulated more than in 2.5 times in responseto inoculation with AM fungus in roots of pea cultivar Finalewas identified using suppressive subtractive hybridization. Weselected eight of them for the present study and supplementedthis list with the well-characterized mycorrhiza-related genesencoding the transcription factor RAD1 and the VAPYRINprotein for analysis . In order to find the sequences of 10 AMspecific genes of cv. Frisson, a BLASTN search of corresponding genes was performed against the newly createdSuperTranscripts transcriptome assembly. The accessions arepresented in Table 8. We compared the RT-PCR expression patterns for chosen genes in cv. Finale as well as cv. Frissonpea plants . The used primers are presented in the Table 1.This allowed the identification of predicted full-lengthsequences for genes of interest. The expression of 10 geneswas investigated by RT-PCR using RNA from control andinoculated roots of cv. Finale and cv. Frisson on several daysafter inoculation (dai) . The cv. Finale was chosento compare the results with previously obtained data for thisgenotype, while cv. Frisson was used for analysis, because thenewly created transcriptome was assembled for this cultivar.Indeed up-regulation of a number of genes was confirmed byRT-PCR using RNA from controls and mycorrhiza-inoculatedpea roots of cv. Frisson and cv. Finale. The expression ofRAD1 and VAPYRIN genes was mainly enhanced at stagesof symbiosis development related to AM fungal colonizationof root cells and arbuscules formation (14\u201328 dai). The similar results were previously obtained for model legume plantM. truncatula The highest levels of expression were found for four genesencoding GDSL-motif lipase/acylhydrolase (147\u200a), MAP kinase (MAPK\u200a), trypsin inhibitor (TI\u200a) and putative lipid-transfer protein (164\u200a) in both genotypes . It isin a good agreement with previous results . It is interesting to note that activation of TI and 164 wasconnected with early stages of AM symbiosis developmentsuch as 7 dai. These markers may be helpful to estimate theinoculation effect, because usually visible signs of inoculationseem to be connected with later stages of symbiosis betweenpea plants and AM fungi like 14 dai. At the same time somecultivar-specific mycorrhiza-related pattern of expression wasfound in our experiments. It was shown for gene 170 withhigh level of expression in cv. Finale, but not in cv. Frisson. Moderate level of expression was shown forthe stress-related genes like 129 and PR6 in our experimentsthat may be due to differences in experimental conditions ascompared to previous study .Studies on model legume plants M. truncatula and Lotusjaponicus (Regel.) K. Larsen resulted in the description ofthe molecular mechanisms underlying the formation andfunctioning of the symbioses . However, for the agriculturally important legume plants, the information regardingthe molecular bases of AM and root nodule symbiosis (RNS)is still limited. As for the garden pea, about 40 regulatorysymbiotic genes are known , of whichabout a half are attributed to the \u2018common\u2019 symbiotic genesneeded for both AM and RNS . The recent development of transcriptome sequencing technologieshas made it possible to analyze the molecular machinery ofsymbiotic nodules and, in particular, to pinpoint the singlenucleotide deletion mutation in important symbiotic geneSym33 (IPD3) . Our first assembledtranscriptome of mycorrhizal pea roots will help in characterization of the key plant genes involved in the regulation ofmycorrhizal symbiosis and, therefore, will be a basis for thefuture advances in our understanding of plant-microbe interactions. 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It consisted of an extremely small population with less than 100 wild individuals. In this study, the complete chloroplast genome of T. parvifolia was assembled using the Illumina data. The complete chloroplast genome of T. parvifolia is 137,106\u2009bp in length. The genome consists of 119 genes in total, including 82 protein-coding genes (PCGs), 4 ribosomal RNA (rRNA) genes, and 33 transfer RNA (tRNA) genes. Phylogenetic analysis indicated that T. parvifolia was closely related to T. fargesii, T. nucifera, and T. fargesii var. yunnanensis with strong support. Torreya parvifolia T.P. Yi, Lin Yang & T.L. Long, belonging to Torreya in Taxaceae family, is a species with extremely small population . Voucher specimen of the species was deposited in the Ecological Security and Protection Key Laboratory of Sichuan Province, China under the accession number: MNU-PHO-0160. The total DNA was extracted with the CTAB method , 4 ribosomal RNA (rRNA) genes, and 33 transfer RNA (tRNA) genes.The complete chloroplast genome of T. parvifolia, we reconstructed a phylogenetic tree using the concatenated 64 PCGs sequences of T. parvifolia and 11 other species. The sequences of each gene were aligned by PRANK (L\u00f6ytynoja T. parvifolia was closely related to T. fargesii, T. nucifera, and T. fargesii var. yunnanensis with strong support (T. parvifolia had 50, 187, and 162 varied sites with T. fargesii, T. nucifera, and T. fargesii var. yunnanensis, respectively. The genetic relationships of other Torreya species were identical with the previous study (Zhang et\u00a0al. T. fargesii did not cluster with T. fargesii var. yunnanensis. T. grandis and T. grandis var. jiulongshanensis were also not clustered together. It was possible because of the mis-identification of materials for sequencing, or the inaccurate published new varieties, which were only based on the characteristics of morphology in past years. In summary, the chloroplast genome of T. parvifolia could help us facilitate the identification and protection for T. parvifolia.To infer the phylogenetic position of support . Within"} +{"text": "The authors wish to make the following erratum in this paper .Research Center for Eco-Environment Sciences, Chinese Academy of Sciences, Beijing 100085, China; ljbao_st@rcees.ac.cn (L.B.); dretfr456@gmail.com (W.C.); chenhao@rcees.ac.cn (H.C.); yswei@rcees.ac.cn (Y.W.)College of Resources and Environment, University of Chinese Academy of Science, Beijing, 100049, ChinaThere are mistakes in the spelling of the first and second institute names of the authors:Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; ljbao_st@rcees.ac.cn (L.B.); dretfr456@gmail.com (W.C.); chenhao@rcees.ac.cn (H.C.); yswei@rcees.ac.cn (Y.W.)College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, ChinaThe corrected spelling should be:The authors apologize for any inconvenience this may have caused."} +{"text": "Dendrocalamus latiflorus Munro), which is a hexaploid species with three subgenomes . One major bamboo species in Asia is Ma bamboo /Cas9 provides straightforward ways for genome editing in many plants were selected to express the sgRNA cassettes containing an additional \u2018guanine\u2019 thereby produces no fluorescence signal was simultaneously cotransformed with CRISPR/Cas9 plasmids in bamboo, whose homolog in maize functions in carotenoid biosynthesis were identified and cloned by a homology cloning strategy contained putative homozygote/biallelic mutations in all subgenomes at the sgRNA1 target site. In some lines, putative homozygote/biallelic mutations exist in one subgenome, while heterozygote or chimeric mutations appear in other subgenomes with homozygote/biallelic mutations in all subgenomes at the sgRNA1 site exhibited albino phenotypes that potentially acts in controlling bamboo height in Ma bamboo were produced using our optimized CRISPR/Cas9 technology. Mutation in GRG1 increased plant height , Fujian Innovative Center for Germplasm Resources and Cultivation of Woody plants (No. 125/KLA15001E), Program for scientific and technological innovation team in university of Fujian province (No. 118/KLA18069A) to Q.Z. The funding bodies were not involved in the design of the study or in any aspect of the data collection, analysis and interpretation of data and in paper writing.The authors declare that they have no conflict of interests.Q.Z. conceived this project. L.F.G., Y.S.Z., X.Q.M. C.T.L. and Q.Z. designed experiments and interpreted the results. S.W.Y., G.C. and M.V.K. performed the experiments and analysed the data. W.J.W., C.Y.C., C.W. and D.W.S. helped to perform the experiments and collect the data. All authors read and approved the submission of this manuscript."} +{"text": "Lobelioideae, the largest subfamily within Campanulaceae, includes 33 genera and approximately1200 species. It is characterized by resupinate flowers with zygomorphic corollas and connate anthers and is widely distributed across the world. The systematics of Lobelioideae has been quite challenging over the years, with different scholars postulating varying theories. To outline major progress and highlight the existing systematic problems in Lobelioideae, we conducted a literature review on this subfamily. Additionally, we conducted phylogenetic and biogeographic analyses for Lobelioideae using plastids and internal transcribed spacer regions. We found that former studies have reached agreement on the southern African origin of Lobelioideae, herbaceous habit and Asian origin of giant lobelioids, the convergent evolution of giant rosette lobelioids, and lastly, the multiple cosmopolitan and independent radiation of lobelioids in Africa, Pacific Basin, and the Hawaiian Islands. Also, Apetahia Baill., Sclerotheca A.DC., and Cyanea Gaudich. are paraphyletic, while Lobelia L., Pratia Gaudich., Centropogon C.Presl, Siphocampylus Pohl, and Isotoma Lindl. are polyphyletic. The taxonomy of these genera, especially Lobelia, is particularly quite frustrating. This calls for further reappraisals using both morphological and molecular data. Lobelioideae, the largest subfamily within Campanulaceae, includes 31 genera and approximately 1200 species with their classification and one nuclear gene, internal transcribed spacer (ITS). These sequences were generated using the NCBI ENTREZ UTILITY (ST April 2020) and double-checked manually at the GenBank database. Additionally, almost all available Campanulaceae complete plastid genomes were manually accessed from the GenBank. The respective plastid regions were extracted using NCBI BLASTN v. 2.9.0+ (Campanulaceae (Abrophyllumornans (F.Muell.) Benth. (Carpodetusserratus J.R.Forst. & G.Forst. (Corokiacotoneaster Raoul (Cuttsiaviburnea F.Muell. (Pentaphragmaellipticum Poulsen (Phellinelucida Vieill. ex Bail. (Rousseasimplex Sm. (Scaevola sp. L. (Stylidiumadnatum R.Br. (Lobelioideae data matrix.We aimed to include as many of the UTILITY program . 2.9.0+ with defnulaceae . The out) Benth. , CarpodeG.Forst. , Corokiaer Raoul , CuttsiaF.Muell. , Pentaph Poulsen , Phellinex Bail. , Rousseaplex Sm. , Scaevola sp. L. and Stylum R.Br. . Taxa votrnF-trnL spacer region had the highest number of sequences while atpF recorded the least dataset and used for ML analyses with the best-selected model. The selection of the best substitution model of the combined dataset did not employ the use of partitioning in this analysis. ITS region was also subjected to ML analyses separately since it formed a tree with a poor resolution when combined with the plastid regions.All the gene regions were aligned separately using MAFFT v. 7.429 with an st Table . Each dast Table to deterst Table . Maximumst Table . DatasetCampanulaceae sp. and Lobelia sp. were unclear and therefore were not assigned any value (region), however, the reconstruction method employed was set to consider missing and inapplicable data.Biogeographic analyses were conducted in MESQUITE v. 3.61 using thhttps://doi.org/10.5061/dryad.3xsj3txfw.The data underpinning the analysis reported in this paper are deposited in the Dryad Data Repository at Campanulaceae species, out of which, nine plastid regions were selected for the combined plastid region datasets. The combined plastid (cp) region dataset included 981 Campanulaceae species, with 298 species from Lobelioideae, which covered almost all Lobelioideae species available in GenBank (Accessed on 1st April 2020) values were quite distinct. The BS value for the Clermontia, Centropogon, Burmeistera, and Siphocampylus clades recorded the least BS values. The combined plastid (cp) dataset showcased a better phylogram with a higher sampled taxon and a clearer resolution Benth. (Trematolobelia) and Brazil Benth. Benth. ), Hawaii) Benth. ). He addLobelia \u00a7 Rhynchopetalum and Lobelia \u00a7 Tylomium). He added that the herbaceous habit of lobelioids is an advanced character. Lobelianicotianifolia Roth have the giant rosette growth form adapted to alpine or mountain conditions, with non-rosette species forming the remainder of the clade. These \u2018rosette-species\u2019 are embedded within the non-rosette species Theeps L.f. . (3) Theeps L.f. . The cir E.Wimm. Sucis Druce , is sistis Druce , and disis Druce .Lobelioideae consisted of up to 31 genera (Lobelioideae genera in our combined plastid (cp) dataset plastid tree J.Murata as the sister to Lobelioideae would not interfere with the African origin of this subfamily, and this corroborated with our biogeographic results. Besides, it is also evident that multiple dispersal events occurred in this subfamily. The basal group consisted of species with their ancestral region in Australasia and Africa. The African group nested some species from Asia, America, and the Pacific Islands. This depicted possibilities of long-distance dispersal and diversification events in some species.eae Fig. . Knox etLobelioideae subfamily. The order of the discussion is according to the positioning of the genera in the phylogram, starting from the basal position to a clade formed by Lobeliaphysaloides, Lheterophyllasubsp.heterophylla and seven members from the Lobelia \u00a7 Delostemon. Pratiaangulata Hook.f. E.Wimm. A.Heller TrematoloA.Heller , with a Apetahia and Sclerotheca form a clade with a BS value of 64. This result confirms that of Apetahia and eight Sclerotheca species. The low BS value might have been a result of incomplete sampling in these two genera. Sclerothecamargaretae F.Br. E.Wimm. Fig. . Clermon a clade with a B 90 Fig. . More branea see , with thSolenopsis is monophyletic with a BS=100. Lobeliaurens L. (Lobelia \u00a7 Stenotium (C.Presl) Lammers formed Downingia formed a monophyletic clade with a BS value of 96. Porterella is sister to Downingia with a BS value of 98. This result corroborates Legenerelimosa (Greene) McVaugh E.Wimm. (BS=100), which is a sister to Downingia and Porterella. Palmerella forms a sister to Downingia, Porterella, and Legenere with a BS of 90 possess the same characteristics e.g. Lobeliaxalapensis Kunth Lammers Lammers (Isotomatridens (E.Wimm.) Lammers E.Wimm. McVaugh (Centropogonluteynii Wilbur (Centropogoncostaricae (Vatke) McVaugh Fig. . Centrop Lammers , Siphoca E.Wimm. , Centrop Zahlbr. , Centrop Zahlbr. , Centrop Lammers , Centrop McVaugh , Centropi Wilbur , Centrop McVaugh , and Sipus Hook. forms an Zahlbr. is sisteade Fig. . Burmeis43) Fig. . The lowsampling . Biogeog America . Our ana America .Lobelia is the \u2018core genus\u2019 among members of the Lobelioideae group (Speirema (Hook.f. and Thomson) Lammers (Trimeris (C.Presl) A.DC. A.DC. , and Pla Lammers , J.Murata with a bootstrap value of 92 C.Presl E.Wimm. Lammers Fig. . This reion Fig. .Lobelia \u00a7 Stenotium. We sampled ten species out of a hundred and forty-four proposed by Lobelialaxa McOwan is sister to a clade of Wimmerellapygmaea (Thunb.) Serra M.B. Crespo and Lammers (Wimmerellahederacea (Sond.) Serra and Lammers (Lobeliamuscoides Cham. (Lobeliajasionoides (A.DC.) E.Wimm. with a BS value of 100 and geographically (both in S. Africa), suggest a biphyletic nature of this section and/or the inclusion of L.jasionoides in Lobelia \u00a7 Stenotium. Lammers . Only on100 Fig. which coLobelia \u00a7 Rhynchopetalum (Giant Lobelioids/Rosettes). We sampled forty-eight out of the sixty-one species J.Murata G.Don G.Don is nestesis Urb. , Lobeliai Graham , Lobelia Hitchc. , Lobeliaicta Sw. , and Lobade Fig. . Biogeogrgens L. , L.portl region . Chen etLobelia \u00a7 Hypsela. Thirteen out of forty-three species within this section were sampled. This section is polyphyletic. It is intercalated with Isotoma, Hypsela, Pratia, and Lithotoma species. Lobeliafugax Heenan, Courtney & P.N.Johnson Lammers Benth. . Biogeography: The ancestral area of this section is Chile Benth. . We samp. & Arn. , Lobelia. & Arn. , Lobeliatupa L. , and Loba Bonpl. , and for 99 Fig. . So far,is Chile . Chen etLobelioideae. We found that previous studies have currently reached an agreement on the southern African origin of Lobelioideae, herbaceous habit, and Asian origin of giant lobelioids, and lastly, the convergent evolution of giant rosette lobelioids. We also found that several genera, such as Lobelia, are polyphyletic and their systematics is particularly frustrating, which calls for further reappraisals using both morphological and molecular data. More so, taxon sampling and sequencing of some genera such as Centropogon, Burmeistera, Siphocampylus, and Clermontia are quite minimal. The phylogenetic analyses in this paper were based primarily on 18 plastid loci; the resolution and support provided by ITS were weak. Future advances in Lobelioideae phylogenetics should include phylogenomic approaches based on hundreds of single-copy nuclear genes and flanking regions, and direct assessment of possible hybridization, incomplete lineage sorting, or other forms of reticulate evolution, to investigate extensively the classification of Lobelioideae.In this study, we conducted a literature review and phylogenetic analyses on"} +{"text": "The global outbreak caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization. As the number of imported SARS-CoV-2 cases is on the rise in Brazil, we use incidence and historical air travel data to estimate the most important routes of importation into the country. Self-declared travel history and subsequent genetic analyses confirmed that the first detected infection was acquired via importation of the virus from Northern Italy.n\u2009=\u200934, as of 10 March 2020). SARS-CoV-2 has been now detected in 7 (26%) of the 27 federal states of Brazil. So far, the transmission of SARS-CoV-2 appears to be primarily sporadic . Here, we analyze data on airline travellers to Brazil in 2019, who departed from countries that had reported local cases of COVID-19 transmission by 5 March 2020. This information provides insights into which Brazilian cities are most at risk for SARS-CoV-2 importation.Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) was first detected in Wuhan, Hubei province, China, on 8 December 2019. SARS-CoV-2 infection can cause coronavirus disease (COVID-19) and can lead to acute respiratory syndrome, hospitalization and death.We used travel data on all air journeys that had a Brazilian city as their final destination during February and March 2019 as a proxy for flight density during the 2020 COVID-2019 outbreak see . We focuBetween February and March 2019, Brazil received 841\u2009302 international passengers in a total of 84 cities across the country . S\u00e3o Paun\u2009=\u200914/29) of the reported imported cases in Brazil have a history of travelling to Italy prior to onset of symptoms, as of 9 March 2020. Six (23.1%) of the confirmed cases that acquired the virus in Italy have been identified in S\u00e3o Paulo and a John Fell Research Fund (grant 005166). N.R.F. is supported by a Sir Henry Dale Fellowship (204311/Z/16/Z). D.D.S.C. is supported by the Clarendon Fund and by the Oxford University Zoology Department.K.K. is the Founder of BlueDot, a social enterprise that develops digital technologies for public health. K.K. and A.W. are employed at BlueDot. D.S.C., L.A., M.K., W.O., J.C., E.C.S., O.G.P. and N.R.F. have no conflicts of interest to declare.D.S.C., L.A. and N.R.F. conceived the idea and wrote the manuscript. D.S.C., L.A., N.R.F., K.K. and A.W. conducted data analysis. D.S.C., N.R.F., L.A., M.U.G.K., W.O., J.C., E.C.S., O.G.P., A.W. and K.K. interpreted data and contributed to writing.Candido_SM_taaa042Click here for additional data file."} +{"text": "Olea europaea L.) is a very important woody tree and favored by consumers because of the fruit\u2019s high-quality olive oil. Chloroplast genome analysis will provide insights into the chloroplast variation and genetic evolution of olives. The complete chloroplast genomes of three accessions were obtained by next-generation sequencing technology. A total of 133 coding regions were identified in the three chloroplast genomes without rearrangement. O. europaea subsp. europaea var. sylvestris and O. europaea subsp. europaea var. frantoio had the same sequences , while O. europaea subsp. cuspidata isolate Yunnan presented a large gap between rps16 and trnQ-UUG genes with six small gaps and fewer microsatellites. The whole chloroplast genomes of 11 O. europaea were divided into two main groups by a phylogenetic tree and O. europaea subsp. cuspidata formed a separate group (Cuspidata group) with the other subspecies (Mediterranean/North African group). Identification of consistency and diversity among O. europaea subspecies will benefit the exploration of domestication events and facilitate molecular-assisted breeding for O. europaea.Olive ( Olea europaea L.) is a famous woody tree in the world and has been cultivated for about five to six thousand years in Mediterranean countries [O. europaea species, which comprises of six subspecies, including O. europaea subsp. europaea (Mediterranean basin), O. europaea subsp. maroccana (Macaronesia), O. europaea subsp. cerasiformis (Macaronesia), O. europaea subsp. guanchica (Macaronesia), O. europaea subsp. laperrinei (Saharan mountains), and O. europaea subsp. cuspidata (from South Africa to South Asia) [O. europaea subsp. europaea, the cultivated olive (O. europaea subsp. europaea var. europaea) and wild olive (O. europaea. subsp. europaea var. sylvestris) are differentiated. There are currently more than 2600 cultivars grown for oil extraction after a long period of domestication with biogeographic conditions and human influence [Olive ,7. For Onfluence . Olive tnfluence .http://www.oleadb.it). The phenomenon of synonyms, homonyms, and unclear genetic relationship still exists among olive germplasms [O. europaea subsp. europaea cv. leccino, O. europaea subsp. europaea cv. farga, and O. europaea subsp. europaea var. sylvestris, were available [Until now, more than 2000 olive accessions have been collected in the Olea databases were classified into five clades with only 15 chlorotypes [europaea subspecies with more variation between different subspecies [O. europaea subsp. cuspidata isolate Yunnan, O. europaea subsp. europaea var. sylvestris, which displayed significant differences from most olive cultivars in tree characteristics, fruit traits, and resistance. As a control, the cultivated olive O. europaea subsp. europaea var. frantoio was also employed to analyze genome variation and genetic association among olive chloroplasts. Through the analysis of structure comparison and evolution relation among all the O. europaea species, this study provides a better understanding of chloroplast variation and genetic evolution of olive at the whole-genome level.Organelle DNA genomes mtDNA and cpDNA are maternally inherited and provide scientists simple and fast methods to study the different genetic backgrounds of olive germplasms . Moleculorotypes . Mariottorotypes and Besnorotypes conductebspecies . Here, wO. europaea subsp. europaea var. frantoio, O. europaea subsp. europaea var. sylvestris, and O. europaea subsp. cuspidata isolate Yunnan. The first two accessions were collected from Italy and Spain, respectively, while O. europaea subsp. cuspidata isolate Yunnan was collected from China. Fresh young leaves (~100 mg) were sampled from the new shoots and frozen in liquid nitrogen for further analysis.Three olive accessions were collected and analyzed in this study including Total DNA was isolated with modified cetyltrimethylammonium bromide (CTAB) method as described by Murray et al. . AgaroseComplete DNA sequencing was done using Illumina\u2019s next-generation sequencing technology. The genome sequencing was performed on the Illumina MiSeq 2000 with paired-end methods (150 bp). The raw sequence reads were filtered using the NGSQC Tool Kit v2.3.3 as follows: (1) remove adapter sequence in the reads; (2) remove the reads whose 5\u2019-end base was unknown; (3) remove the reads with the quality value \u2264 Q20; (4) remove reads whose unknown bases \u2265 10%; (5) remove reads whose length was less than 50 bp.O. europaea subsp. europaea var. manzanilla (FN996972.1) as a reference. Sequence extension, hole filling, and splicing were performed with paired-read iterative contig extension (PRICE) and MITObim (https://github.com/chrishah/MITObim). The chloroplast genes were annotated using the DOGMA and UGENE ORFs finder tool [The quality of the raw reads was assessed by FastQC and carrder tool and visuder tool .O. europaea subsp. europaea var. frantoio and O. europaea subsp. europaea var. sylvestris, and MT182985 for O. europaea subsp. cuspidata isolate Yunnan.Each of the assembled cpDNA sequences has been submitted to GenBank and acquired the following accession numbers: MT182984 and MT182986 for O. europaea chloroplast genomes sequenced here, the other three subspecies genomes, including O. europaea subsp. laperrinei (MG255765.1), O. europaea subsp. guanchica (MG255764.1), O. europaea subsp. maroccana (FN998900.2), were used for comparative genomic analysis. Sequence identity and rearrangement were performed using the mVISTA program with LAGAN mode [Except for the three GAN mode and MauvGAN mode .http://pgrc.ipk-gatersleben.de/misa/). Four types of repeat sequences, including forward, reverse, complement, and palindrome sequences, were determined by REPuter software with a minimum repeat size of 20 bp as described by Liu et al. [Repetitive simple sequence repeat (SSR) sequences were analyzed with MISA software as the outgroup. In addition to the three O. europaea chloroplast genomes sequenced here, the other eight genomes included O. europaea subsp. laperrinei (MG255765.1), O. europaea subsp. guanchica (MG255764.1), O. europaea subsp. maroccana (FN998900.2), O. europaea subsp. europaea var. bianchera (NC_013707.2), O. europaea subsp. europaea var. manzanilla (FN996972.1), O. europaea subsp. cuspidata isolate Maui 1 (FN650747.2), O. europaea subsp. cuspidata isolate Guangzhou 1 (FN996944.1), and O. europaea subsp. cuspidata isolate Almihwit 5.1 (FN996943.2). These were obtained from the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov). MAFFT 7.427 (https://www.ebi.ac.uk/Tools/msa/mafft/) and Gblocks were used for multi-sequence alignment and editing. The phylogenetic tree was built using IQTREE 1.6.10 software (http://www.iqtree.org) with maximum likelihood method (GTR + I + G) and edited with Figtree 1.4.3 software (http://tree.bio.ed.ac.uk/software/figtree/).All of the nucleic acid sequences of 11 O. europaea subsp. europaea var. frantoio, O. europaea subsp. europaea var. sylvestris, and O. europaea subsp. cuspidata isolate Yunnan were 155,886, 155,886, and 155,531 bp with 42512X, 35953X, and 48376X depth, respectively. After performing the de novo and reference-guided assembly with minor modifications, the complete chloroplast genome sequences of three O. europaea accessions were obtained (O. europaea subsp. europaea var. frantoio and O. europaea subsp. europaea var. sylvestris shared the completely same sequence (O. europaea subsp. europaea var. manzanilla (FN996972.1) [O. europaea had two copies of inverted repeat separated by large single-copy and small single-copy regions . The gen regions ; Table 2O. europaea chloroplast genomes, the gene structures of O. europaea subsp. europaea var. frantoio, O. europaea subsp. europaea var. sylvestris, and O. europaea subsp. cuspidata isolate Yunnan were drafted with the other three O. europaea subspecies, including O. europaea subsp. laperrinei (MG255765.1), O. europaea subsp. guanchica (MG255764.1), and O. europaea subsp. maroccana (FN998900.2) obtained from NCBI (https://www.ncbi.nlm.nih.gov). The six O. europaea chloroplast genomes showed collinear gene organization with no rearrangement that occurred were right at the border of IRa and SSC, while in O. europaea subsp. guanchica and O. europaea subsp. maroccana, the ycf1 gene was located across both IRa and SSC regions.We also found that the ycf1 gene at the boundary between IRa and SSC had different expansion and contraction. As in O. europaea chloroplast genomes were also studied. There were 68, 68, and 59 microsatellites identified in O. europaea subsp. europaea var. frantoio, O. europaea subsp. europaea var. sylvestris, and O. europaea subsp. cuspidata isolate Yunnan, respectively as the outgroup and wild (O. europaea subsp. europaea var. sylvestris) olive [O. europaea subsp. europaea var. sylvestris was first sequenced and showed exactly the same as O. europaea subsp. europaea var. frantoio. They also displayed a high similarity with cultivated olives, indicating that few differentiation events were present in O. europaea subsp. europaea chloroplasts. More exploration of domestication events should be conducted to study the genome sequences.Six olive subspecies are recognized as before ,6,7. Amos) olive ,35. The s) olive ,35,36,37s) olive . Here, tO. europaea occupied two main groups, the Mediterranean/North African and the Cuspidata groups, which confirmed previous research using polymorphic sites [cuspidata and other subspecies. Although O. europaea subsp. cuspidata isolate Yunnan had the same number of coding regions without rearrangement, a large gap exists between rps16 and trnQ-UUG with six small gaps was present. Moreover, 59 microsatellites were identified from O. europaea subsp. cuspidata isolate Yunnan, compared to 68 found in O. europaea subsp. europaea. The results indicate high diversity between Cuspidata and Mediterranean/North African groups and further benefit the development of molecular markers.The phylogenetic analysis based on the whole chloroplast sequences showed that ic sites ,24,39. TOlea, only the cultivars of O. europaea are economically valuable, and O. europaea shows low genetic variation and obvious regionalization. O. europaea subsp. cuspidata has no economic value other than as an ornamental. The diversity of O. europaea subsp. europaea with other subspecies identified here could be used as an important gene resource to broaden the genetic background of olive cultivars through conventional or molecular breeding methods. They appear to be compatible using the conventional breeding methods. Ma et al. [O. europaea subsp. europaea var. frantoio and O. europaea subsp. cuspidata isolate Yunnan, had stronger abiotic stress-resistance tolerance, more vigorous vegetative growth, and a later flowering stage compared to the female parent. Our findings will provide more information on O. europaea subsp. cuspidata isolate Yunnan for molecular assisted breeding.In the genus a et al. ,41 repor"} +{"text": "The authors make the following correction to this paper after the final publication of the work : The autThe Author Contributions section has been updated as follows: B.H. and M.B. designed the experiments. Experimental work and ADMET Predictor simulations were performed by B.H. and M.B. performed the modeling experiments. P.A. conceptualized the research subject. G.L.A and G.E.A. supervised and co-financed the project. R.C. reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript."} +{"text": "This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contribution section now reads:\u201cConceptualization, R.N.B., B.P. Execution of Experiments, A.A., M.L., N.V., S.N., M.S., B.O.R.; Data Analysis and Review, A.A., M.L., N.V., S.N., M.S., P.I., B.O.R., B.P., R.N.B., A.T., B.L.K.M.; Manuscript Preparation, A.A., M.L., N.V., S.N., M.S., P.I., B.O.R., B.P., R.N.B.; Funding Acquisition, B.P., B.M.\u201dIn addition, the original Acknowledgements statement contained information that should have been given in the Competing Interests section. This Competing Interests section has been updated to include information about the omitted author and now appears in the Article as below:\u201cA.A., N.V., S.N., P.I., A.T., B.O.R., B.L.K.M. and R.N.B. are employees and equity shareholders of Sentien Biotechnologies. B.P. and B.L.K.M. are also equity shareholders and B.P. is an inventor of the technology with licensed patents to Sentien for commercialization. M.S. is a former employee of Sentien Biotechnologies and is at present an employee at Mitobridge, Inc. with no other competing financial interests. M.L. is an inventor of this technology and at present time an employee of Vor BioPharmaceuticals with no other competing financial interests.\u201dFinally, the Acknowledgements,\u201cA.A., N.V., S.N., P.I., A.T., B.O.R., B.L.K.M. and R.N.B. are employees and equity shareholders of Sentien Biotechnologies. B.P. and B.L.K.M. are also equity shareholders and B.P. is an inventor of the technology with licensed patents to Sentien for commercialization. M.L. is an inventor of this technology and at present time an employee of Vor BioPharmaceuticals with no other competing financial interests. This research was conducted with private funding and support under SBIR Grant No. R44DK085766 and R44HL128659 awarded by the National Institutes of Health as well as R01EB012521 and R21AI134116.\u201dnow reads:\u201cThis research was conducted with private funding and support under SBIR Grant No. R44DK085766 and R44HL128659 awarded by the National Institutes of Health as well as R01EB012521 and R21AI134116.\u201d"} +{"text": "AlCl3 \u00b7 6\u041d2\u041e at a concentration of 99 mM allowed us to identify the most tolerant small radish and radishaccessions that originate from countries with a wide distribution of acidic soils. In a result, it was possible to determinethe intraspecific variability of small radish and radish plants in the early stages of vegetation and to identifygenotypes that are contrasting in their resistance to aluminum. We recommend the AlCl3 \u00b7 6\u041d2\u041e concentration of83 mM for screening the aluminum resistance of small radish and 99 mM for radish. The modified method that wedeveloped is proposed as a rapid diagnosis of aluminum tolerance for the screening of a wide range of R. sativusgenotypes and a subsequent study of contrasting forms during a longer cultivation of plants in hydroponic culture as well as reactions ofplants in soil conditions.Radish and small radish (Raphanus sativus L.) are popular and widely cultivated root vegetables in theworld, which occupy an important place in human nutrition. Edaphic stressors have a significant impact on theirproductivity and quality. The main factor determining the phytotoxicity of acidic soils is the increased concentrationof mobile aluminum ions in the soil solution. The accumulation of aluminum in root tissues disrupts the processesof cell division, initiation and growth of the lateral roots, the supply of plants with minerals and water. The study ofintraspecific variation in aluminum resistance of R. sativus is an important stage for the breeding of these crops. Thepurpose of this work was to study the genetic diversity of R. sativus crops including 109 accessions of small radishand radish of various ecological and geographical origin, belonging to 23 types, 14 varieties of European, Chineseand Japanese subspecies on aluminum tolerance. In the absence of a rapid assessment methodology specialized forthe species studied, a method is used to assess the aluminum resistance of cereals using an eriochrome cyanine Rdye, which is based on the recovery or absence of restoration of mitotic activity of the seedlings roots subjectedto shock exposure to aluminum. The effect of various concentrations on the vital activity of plants was revealed:a 66-mM concentration of AlCl Acidic soilsin the world make up 30\u201340 % of arable ground and upto 70 % of ground that can potentially be used as arable. In Russia in 2019, out of 50 millionhectares of excessively acidic soils, strongly and moderatelyacidic ones occupy from 25 to 35 million hectares, whichis about 30 % of all arable ground .Aluminum is one of the most abundant metals in the earth\u2019crust and is considerednon-toxic to plants when the soil solution is neutralor slightly alkaline. Natural processes or human activitiescan lead to an increase acidity in soil, in result of whichthe solubility of aluminum increases, and the content ofits mobile forms . So, aluminumaffects on a series of cellular processes, including the rateof cell division, and disrupts the properties of protoplasmand cell walls.The toxicity of AlPlants are subdivided into resistant and sensitive byalumotoxicity, varietal differences may be stronger thanspecies .Plants have developed several mechanisms of resistance toaluminum during the evolutionary process . In recent years, themolecular mechanism of aluminum tolerance in agriculturalcrops, primarily in cereals, has been actively studied.Significant progress has been achieved in understanding the physiological and molecular mechanisms of aluminumtolerance in Arabidopsis , rapeseed, maize , soybean, rice , sorghum ,rye and wheat.At present, aluminum resistance is considered as a complexphytoecological problem, from the solution of whichan obtaining of guaranteed productivity crops on acidicsoils depends. The identification of genes and mechanismsof aluminum tolerance makes possible Al-tolerant speciesand cultivars of agricultural crops breeding using molecularand transgenic approaches .The basic critical parameter for the successful creationof stress tolerant cultivars is the genetic diversity of theinitial material for this indicator as a material for selection. The successful creationof aluminum-resistant cultivars of agricultural plants isbased on a significant variability in the trait of aluminumtolerance and relatively simple methods of screening andbreeding . Thesearch for genotypes with a high tolerance to Al is of greatimportance for agriculture on acidic soils.Radish and small radish belong to the species Raphanussativus L., for which two primary geographical centers oforigin are known \u2013 Mediterranean and Asian , herewith the Asian center was divided into secondarycenters in the classification of M.A. Shebalina andL.V. Sazonova (1985): South West Asian, East Asian,South Asian tropical. Small radish is a mutant form ofradish; artificial selection was carried out on the featureof dwarfishness of plants in the vegetative period of ontogenesis,while the plants of the reproductive period practicallydo not differ in habitus from the radish plants. The processes of mutagenesis in R. sativus are determined bythe climatic conditions of the places of origin of culturalforms. Cultivation of radish began 4\u20133 thousand BC, smallradish was introduced into culture much later \u2013 the firstinformation about it appeared in Italy at the beginning ofthe 16th century.Small radish cultivars are assigned to 6 botanical varietiesand 16 types, radish \u2013 14 varieties and 20 types, whichdiffer in a complex of morphological, phenological, physiological,biochemical and economically valuable traits.Small radish and radish are popular and widely cultivatedroot vegetable crops around the world that play an importantrole in human nutrition. They are valued for their highproductivity, manufacturability, good taste and valuablebiochemical composition.For the growth and development of small radish and radish,the neutral reaction of the soil solution (pH 6.0\u20138.0) isthe favorable. Plants are especially sensitive to low acidityin the initial periods of growth. Most of the spaces undersmall radish and radish in the world are located on theterritory occupied by acidic soils; alumotoxicity makes anegative contribution to the decrease of the productivityand quality of these crops. Therefore, modern cultivarshave to be tolerant to Al, alongside with signs of high productivity,resistance to pathogens, manufacturability, etc.The first stage in such studies should be the search in thegene pool of R. sativus for forms resistant to aluminum inan acidic environment.Several diagnostic methods have been used to assessthe degree of plant resistance to aluminum . Often used laboratory screening techniques arebased on various modifications of methods for germinatingseeds in an aquatic culture in the presence of toxic aluminumconcentrations . The advantage of such techniques is thesimplicity of execution, low time spent, high throughput,and the ability to diagnose genotypes at the early stages ofontogenesis. A series of studies revealed a quite high correlation(r = 0.71\u20260.85) between the results of laboratoryassessments of resistance at the early stages of developmentwith the data of field and vegetation tests of adult plants.Plant resistance can be assessed in laboratory tests bythe degree of damage of the seedlings roots by aluminumusing hematoxylin and eriochromecyanine R . This method was successfullyapplied to assess the intraspecific variability of aluminumtolerance in rice , peas, maize,wheat, and sorghum with hematoxylin, andwith wheat, rye, triticale , aegilops, oats, maize and peas witheriochrome cyanine R.Researches of R. sativus root crops resistance to damageof aluminum have practically not been conducted.The toxicological effect of aluminum-based coagulantson various crops, including individual radish genotypes,was studied in the work of K. Zhang and Q. Zhou (2005).Oil radish (Raphanus sativus var. oleifera Metzg.) hasthe greatest potential for phytoextraction of fluoridesfrom contaminated soils . J. Rajand L.R. Jeyanthi (2014) studied the effect of aluminumchloride on the germination of R. sativus seeds, and it wasfound that the maximum allowable limit for Al to maintainviability is 10 mM. The study of intraspecific variation ofR. sativus aluminum resistance is an important stage forthe breeding of these crops.3 \u00b7 6H2O),which differentiates small radish and radish accessions accordingto the degree of aluminum resistance, to identify themost resistant genotypes, and to determine their botanical,agrobiological, and geographic confinedness.The purpose of this work was to study the genetic diversityof the VIR world wide R. sativus collection on thealuminum tolerance trait. The tasks were to determine thetoxic concentration of aluminum chloride .In the absence of a rapid assessment methodology specializedfor the studied species, the method of the aluminumresistance evaluation of cereals using an eriochromecyanine R dye is used , which is based on therecovery or absence of restoration of the seedlings rootsmitotic activity subjected to shock exposure to aluminum.2, 0.4 KNO3, 0.25 MgCl2,0.01 (NH4)2SO4, 0.04 NH4NO3; pH 4.2 . After germinating the seeds for 3 days, the not viableones were rejected. Then, the cuvettes with seedlings wereplaced in a freshly prepared nutrient solution supplementedwith aluminum chloride (AlCl3 \u00b7 6H2O) and incubated for24 h.The experiments were carried out in a climatic chamberwith an illumination 7000 Lx, a temperature 19\u201321 \u00b0C anda photoperiod 16 h. Seeds (50 pieces of each accession)were placed in special cells for seeds and a mesh bottom,which were placed in 6-liter containers, placing them onthe surface of the nutrient solution. The nutrient solutioncontained (mM): 0.4 CaCl3 \u00b7 6H2O concentrationsof 66, 83, and 99 mM, which had a toxic effect onplants and inhibited root growth in degrees under the usedconditions. After that, the cuvettes were placed in a freshnutrient solution without aluminum and incubated for 48 h.During the indicated time, reparation processes took placein the roots (restoration of the mitotic activity of cells)and the roots grew. The seedlings were washed with cleanwater and the roots were stained by immersing the cuvettesin a 0.1 % solution of eriochrome cyanine R for 10 min.The excess dye was washed off with clean water, and theroots were dried with filter paper. The zone of root tissuedamagewith aluminum was colored violet after stainingwith eriochrome cyanine R. Plant resistance to aluminumwas determined by the length of root tip regrowth. For eachaccession two independent experiments were carried outin two-fold repetition.Thus there are no descriptions of the R. sativus cropsaluminum resistance in the publications, based on the preliminary experiments, we used AlClStatistical data processing was performed by the methodof analysis of variance using the STATISTICA v.12.0program , by the method of clusteranalysis (Ward\u2019s method) using the PAST program .3 \u00b7 6H2O (see the Table).At the first stage, we investigated the effect of differentaluminum concentrations on small radish and radish. Ingeneral, the results of our research have shown that anexcess of aluminum and hydrogen (low pH) in the nutrientsolution negatively affects the growth and development ofthe embryonic roots of small radish and radish seedlings.We observed significant differences between R. sativusaccessions in root regrowth at all tested concentrations ofAlClThe aluminum chloride concentration of 66 mM had aweak toxic effect on R. sativus accessions. In most of thesmall radish and radish accessions, the mitotic activity ofseedling root cells was restored after the shock exposureto aluminum. In 70.4 % of the small radish accessions and92.7 % of the radish, the root growth was rather high (morethan 1.0 cm), that indicates a normal further development.22.2 % of the small radish accessions and 5.5 % of the radishshowed an average root growth (0.5\u20131.0 cm); in foursmall radish accessions and one radish, the root growthwas less than 0.5 cm.3 \u00b7 6H2O of 83 mM, a largedifferentiation of the accessions was observed. In 29.6 %of the small radish accessions and 70.9 % of the radish, theroot growth was more than 1.0 cm, the average regrowth(0.5\u20131.0 cm) was observed in 51.9 % of the small radishand 25.5 % of the radish. Root growth of less than 0.5 cmwas observed in 18.5 % small radish and 3.6 % radishaccessions.At a concentration of AlClAt an aluminum chloride concentration of 99 mM, therewas no further root growth in 13.0 % of the small radishand in 7.3 % of the radish accessions. A slight root growth(up to 0.5 cm) was observed in 46.3 % of small radish and 14.5 % of radish. Root regrowth by 0.5\u20131.0 cm wasobserved in 33.3 % of small radish and 41.8 % of radish.Normal root growth after exposure of this concentration ofthe toxicant was observed in only 7.4 % of the small radishand 36.4 % of the radish accessions.So, the differences were most clearly manifested betweensmall radish accessions at Al concentration of 83 mM, andbetween radish accessions at a 99 mM concentration at differentstressor intensity. These concentrations were used forfurther evaluation of polymorphism because their negativeimpact showed the maximum differentiating ability.The accessions with the minimum length of root regrowthhad an intense violet coloration of the root areasthat grew upon the addition of mobile aluminum, and theaccessions with the maximum length of the root regrowthhad a weak but detectable staining .The accessions of small radish and radish were dividedinto several statistically significant groups according to thelength of root regrowth, depending on the concentration ofaluminum . The accessions were characterized by awide range of root growth at a concentration of 66 mM \u20130.15\u20132.65 cm and 0.38\u20133.05 cm (radish),this variability divided the samples into seven and eightgroups, respectively.Small radish accessions were divided at a concentrationof 83 mM into four groups with a range of variability from0.20 to 1.50 cm. The first group consisted of five accessionswith root growth less than 0.40 cm; these accessions areof var. rubescens Sinsk. from Canada and Hungary. Thesecond group included the largest number of accessions(24 accessions) from the countries of Minor Asia andCentral Asia and Africa. The third group was representedby accessions of various types from Europe and SouthAmerica. The fourth group included nine accessions withroot regrowth more than 1.20 cm; these accessions are fromRussia, China, Turkey, Hungary, Iceland, and Tanzania.Radish accessions were divided at a given concentrationinto five groups with a range of 0.46\u20132.25 cm. Accessionswere absent with root regrowth after exposure to thisconcentration less than 0.40 cm. The first group included8 accessions with root growth from 0.41 to 0.80 cm fromJapan, Russia, China and Uzbekistan. The second groupwas represented by accessions from Central Asia, Vietnam,South Korea, Egypt and Japan. The third and fourthgroups were the largest and included 31 accessions withroot growth more than 1.20 cm from Japan, South Korea,countries of Europe and Central Asia, as well as from theUSA, Chile and Russia. The fifth group was representedby 3 accessions from Japan and Belarus with root regrowthof more than 2.0 cm.The small radish and radish accessions were divided ata concentration of 99 mM into four groups in the rangefrom 0.00 to 1.45 cm. The first group consisted of 26 smallradish accessions, of which 7 accessions did not have rootregrowth; these accessions had different geographic origin,but most accessions were from Canada, Russia, China, and Central Asia. The first group of radish included only7 accessions, of which four did not grow roots; this groupincluded accessions from China, Ukraine, Belarus, andRussia. The second group of small radish was formed byaccessions from Europe and South America, as well assome accessions from Azerbaijan, Tajikistan and Libya.This group of radish includes accessions from Russia, thecountries of Central Asia, China and South Korea. Thethird group of small radish included 6 accessions fromChile, Russia and Syria, radish \u2013 25 accessions mainlyfrom Japan, South Korea, as well as from Chile, Turkey,Russia, Germany and the USA. The fourth group in smallradish was formed by only one accession from Russia(k- 1666), in radish \u2013 6 accessions from Japan, South Koreaand Kazakhstan.3 \u00b7 6H2O.Accordingto the screening results using the Ward\u2019s method,the small radish and radish accessions were divided intotwo big groups, each of the groups was divided into clustersaccording to the degree of aluminum resistance, the totalnumber of which was five. The first group is representedby two clusters, the second \u2013 by three.Figure 3 shows a dendrogram based on the results ofcluster analysis of root growth in R. sativus accessionsafter exposure to toxic concentrations of AlCl3 \u00b7 6H2O andrelatively high at concentrations of 83 and 99 mM. Thesecond cluster combined accessions of small radish andradish with root growth more than 1.0 cm after exposureto all three toxic concentrations of Al. The cluster is dividedinto two subclusters. The first subcluster contains anaccession of small radish from Russia , accessions of Japanese radish from Japan and SouthKorea, two accessions of European winter radish fromGermany and the USA (var. niger (L.) Sinsk.) and anaccession of Chinese radish from Chile (var. lobo). Thesecond subcluster includes accessions of small radish fromHungary (var. chloris Alef.), Syria (var. rubescens Sinsk.), Argentina (var. striatus Sinsk.) and Russia (var. roseusSazon.), accessions of Chinese radish from Kazakhstan,China and South Korea (var. virens Sazon.), Japan, Russia,Iraq and Afghanistan (var. rubidus Sazon.) and accessionsof Japanese radish from Japan, South Korea andVietnam.The first small cluster included accessions of Japaneseradish from Japan and South Korea and Belarus and an accessionof Chinese radish from Egypt; they showed a largeroot growth at a concentration of 66 mM AlClThe third small cluster unites small radish accessions,which showed little or no root regrowth at all concentrationsused. The cluster included accessions from France,Pakistan (var. striatus Sinsk.), Canada, Hungary, Ethiopia,Lebanon , China andIndia (var. roseus Sazon.).The fourth cluster is represented by accessions of smallradish and radish, in which root regrowth after exposureto toxic concentrations of 83 and 99 mM was average (upto 1.0 cm). The cluster is divided into three subclusters.The first subcluster included small radish accessions ofvar. striatus and var. rubescens, one accession each ofvar. radicula and var. roseus, Chinese radish from Kazakhstan(var. lobo) and China (var. roseus Sazon.) and Japaneseradish from Japan. The second subcluster unites accessionsof small radish from Chile, the Netherlands, Hungary(var. rubescens Sinsk.), accessions of European radish fromRussia, Egypt (var. niger (L.) Sinsk.) and Chinese radishfrom South Korea (var. lobo), China (var. roseus Sazon.).The third subcluster includes accessions of small radishvar. rubescens from Chile, Turkey and Hungary, accessionsof European winter radish from Ukraine (var. hybernus),and an accession of pink Chinese radish from China.The fifth cluster includes accessions of small radish andradish, with partial or complete inhibition of root growth ata concentration of 99 mM and an average root regrowth atother concentrations. The cluster is divided into three subclusters.The first subcluster unites accessions of Chineseradish of Central Asian origin, Japanese radish from Japanand South Korea, and an accession of small radish fromChile. The second subcluster mainly includes accessionsof small radish from Russia, China and Tanzania and twoaccessions of radish from Belarus and China. The thirdsubcluster is mainly represented by accessions of smallradish of Central Asian origin and several accessions ofradish from Russia and Ukraine.Genetic processes were of great importance in the phylogenesisof radish and small radish: recombination, mutationsat the chromosomal level, expression of inactive genesand changes in the frequencies of alleles that control traitsand determine the phenotype of the plant; they occurredunder natural and artificial selection in various ecologicaland geographical conditions . Thelarge intraspecific diversity of forms of R. sativus at thediploid level of development is explained by spontaneousgene and inherited somatic mutations . In our previous studies, we found that the limits ofvariability of quantitative traits insmall radish and radish are very large . For example, theamplitude of variation of the most important features: theduration of the period of vegetation is 18\u201395 days; rootweight is 2\u201375 and 150\u20131100 g (radish); thediameter of the leaf rosette is 8\u201345 cm; root shape: roundflat,round, round-oval, oval, cylindrical, fusiform, conical;content of ascorbic acid 18\u201355 mg/100 g, etc.According to the literature data, it is known that, ingeneral, small radish and radish are resistant to the actionof heavy metals and have a high accumulating ability ofheavy metals in the root . Japanese radish accumulatesless toxic elements in roots; it is more resistant to pollutionby such heavy metals as lead, cadmium, nickel, zinc,vanadium, chromium, arsenic. The response of Japaneseradish to soil pollution is varietal specific . Crops of R. sativus are accumulatorsof heavy metals; they have been proposed for phytoremediation. Also, radish is a vegetablecrop moderately sensitive to salt stress .The study of R. sativus crops revealed high intraspecificvariability in aluminum resistance. In general, radish wasmore resistant to alumo stress than small radish regardlessof concentration, which is probably related to the processesof morphogenesis.As a result of grouping accessions according to the lengthof root regrowth after exposure to various toxic concentrationsof aluminum chloride , it was found thatthe accessions of both crops form four groups with a rootregrowth range from 0 to 1.6 cm at a concentration of 83 and99 mM. Accessions of R. sativus reacted weakly to low concentrationsof AlCl3 \u00b7 6H2O, the mitotic activity of seedlingroot cells was restored after the shock effect of aluminum.With an increase of concentration, intraspecific differencesin the crops begin to appear. The intensity of staining witheriochrome cyanine R characterizes the concentrationofmobile forms of aluminum, which in turn correlateswithaluminum tolerance . If, aftertreatment with aluminum, the concentration of its activeforms is low, then the mitotic activity of cells is restored atthe root, the root grows back, and after the staining zone,an unstained growth appears . So, theintensity of the staining can serve as an additional indicatorof the degree of aluminum tolerance associated with theconcentration of the toxicant in the root tissues.Based on the obtained results, we propose a resistancescale for R. sativus crops based on aluminum tolerance: rootgrowth up to 0.40 cm \u2013 sensitive, from 0.41 to 0.80 cm \u2013weakly resistant, from 0.81 to 1.20 cm \u2013 medium resistant,more than 1.21 cm \u2013 highly resistant.3 \u00b7 6H2O concentration of 99 mM made possibleto identify the most tolerant small radish samples (in descendingorder): Virovsky bely , Janosnapi , Local , and radish:Hakata haruwaka , Akasuji ,Hariou , Jangsu .The AlClAccording to the results of cluster analysis, it was revealedthat the first and second clusters combine highlyresistant and medium-resistant radish accessions and highlyresistant small radish accessions, the third cluster containssensitive and low-resistant small radish accessions, and thefourth and fifth clusters mainly contain medium-resistantsmall radish accessions and low-resistant and unresistantradish accessions. It was revealed that accessions of R. sativusof Central Asian origin , as well as from African countries were found to be weak resistant and sensitive toalumostress. The soils of these countries are characterizedby a neutral or slightly alkaline reaction of the soil solution,what, probably, determines the low resistance of the accessionsto low acidity and alumostress. Medium-resistantaccessions were mainly of European origin , as well as from the USA and Chile.In these countries, there is an active breeding of thesecrops in various directions. Accessions of small radish andradish from Russia, Hungary, Turkey, China, Japan, SouthKorea, and Kazakhstan had varying degrees of resistance;accessions of the same geographic origin could be both aluminumtolerant and sensitive to aluminum. Perhaps this isdue to the presence of both acidic and neutral/alkaline soilsin these countries, as well as to the direction of breedingwork with these crops. The most aluminum-tolerant wereaccessions of Japanese radishfrom Japan of Kameido typeand Shiroagiri type from South Korea, local accessions ofgreen Chinese radish from Kazakhstan and accessions ofChinese small radish of the Russian breeding, which wereobtained by selection and hybridization from the populationof Asian radishes.So, the Raphanus sativus species is polymorphic notonly in phenotypic and biochemical characteristics, butalso in the degree of resistance to various abiotic stresses.3 \u00b7 6H2O for assessing the aluminum tolerance of smallradish, and a concentration of 99 mM for assessing radish.The method developed by us is proposed as an expressdiagnostics of aluminum tolerance for rapid screening of a wide range of R. sativus genotypes and subsequent studyof contrasting forms during longer plant cultivation inhydroponic culture , aswell as plant reactions in soil conditions.As a result of this study, we found that excess concentrationsof mobile aluminum and hydrogen (elements of acidicsoils) in the root zone lead to a negative effect on the growthand development of embryonic roots of small radish andradish accessions. 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Repeat variants forthe SbMATE transporter protect sorghum roots from aluminumtoxicity by transcriptional interplay in cis and trans. Proc.Natl. Acad. Sci. USA. 2019;116(1):313-318. DOI 10.1073/pnas.1808400115.Ngo L.K., Pinch B.M., Bennett W.W., Teasdale P.R., Jolley D.F.Assessing the uptake of arsenic and antimony from contaminatedsoil by radish (Raphanus sativus) using DGT and selectiveextractions. Environ. Pollut. 2016;216:104-114. DOI 10.1016/j.envpol.2016.05.027.Peng W., Wu W., Peng J., Li J., Lin Y., Wang Y., Tian J., Sun L.,Liang C., Liao H. Characterization of the soybean GmALMTfamily genes and the function of GmALMT5 in response to phosphatestarvation. J. Integr. Plant Biol. 2018;60:216-231. DOI10.1111/jipb. 12604.Pereira J.F., Zhou G., Delhaize E., Richardson T., Zhou M.,Ryan P.R. Engineering greater aluminium resistance in wheatby over-expressing TaALMT1. Ann. Bot. 2010;106(1):205-214.DOI 10.1093/aob/mcq058.Raj J., Jeyanthi L.R. Phytoremediation of aluminium and lead usingRaphanus sativus, Vigna radiata and Cicer arietinum. J. Chem.Pharm. Res. 2014;6(5):1148-1152.Roy A.K., Sharma A., Talukder G. Some aspects of aluminum toxicityin plants. Bot. Rev. 1988;54(2):145-178.Shebalina M.A., Sazonova L.V. The \u0421ultural Flora of the USSR.Vol. 18. Root Plants. Leningrad: Agropromizdat Publ., 1985. (inRussian)Sokolova L.G., Zorina S.Y., Belousova E.N. Zonal cultivars offield crops as a reserve for the phytoremediation of fluorides pollutedsoils. Int. J. Phytoremediation. 2019;21(6):577-582. DOI10.1080/ 15226514.2018.1540545.Suhoverkova V.E. Soil acidity: trends and control. Zhurnal Agrobizness= Journal Agribusiness. 2015;6(34):60-62. (in Russian)Sun X., Xu L., Wang Y., Luo X., Zhu X., Kinuthia K.B., Nie Sh.,Feng H., Li Ch., Liu L. Transcriptome-based gene expressionprofiling identifies differentially expressed genes critical for saltstress response in radish (Raphanus sativus L.). Plant Cell Rep.2016;35(2):329-346. DOI 10.1007/s00299-015-1887-5.Vavilov N.I. The Doctrine of the Origin of Cultivated Plants afterDarwin. Selected Works. Vol. 5. Moscow; Leningrad, 1965. (inRussian)Vishnyakova M.A., Semenova E.V., Kosareva I.A., KravchukN.D., Loskutov S.I., Puhal\u2019skii I.V., Shaposhnikov A.I.,Sazonova A.L., Belimov A.A. Method for rapid assessment ofaluminum tolerance of pea (Pisum sativum L.). SelskokhozyaystvennayaBiologiya = Agricultural Biology. 2015;50(3):353-360.DOI 10.15389/agrobiology.2015.3.353eng.Vorob\u2019ev M. Liming of acidic soils in Russia: problems and currentapproaches. 2019. Available at: https://glavagronom.ru/articles/Izvestkovanie-kislyh-pochv-v-Rossii-problemy-i-aktualnye-podhody(in Russian)Wang D., Wen F., Xu Ch., Tang Y., Luo X. The uptake of Cs andSr from soil to radish (Raphanus sativus L.) \u2013 potential for phytoextractionand remediation of contaminated soils. J. Environ.Radioact. 2012;110:78-83. DOI 10.1016/j.jenvrad.2012.01.028.Wang H., Chen R.F., Iwashita T., Shen R.F., Ma J.F. Physiologicalcharacterization of aluminum tolerance and accumulation intartary and wild buckwheat. New Phytol. 2015;205(1):273-279.DOI 10.1111/nph.13011.Xu L., Wang Y., Zhang F., Tang M., Chen Y., Wang J., Karanja B.K.,Luo X., Zhang W., Liu L. Dissecting root proteome changes revealsnew insight into cadmium stress response in radish (Raphanussativus L.). Plant Cell Physiol. 2017;58(11):1901-1913. DOI10.1093/pcp/pcx131.Yokosho K., Yamaji N., Ma J.F. Isolation and characterisation oftwo MATE genes in rye. Funct. Plant Biol. 2010;37(4):296-303.DOI 10.1071/FP09265.Zhang K., Zhou Q. Ecological toxicity of aluminum-based coagulanton representative corps in neutral environment. J. Appl.Ecol. 2005; 16(11):2173-2177."} +{"text": "Scientific Reports 10.1038/s41598-020-65784-6, published online 01 June 2020Correction to: This Article contains errors. The Acknowledgements section in this Article is incomplete.\u201cWe would like to thank Matthew Smith for providing the Green Castle, Jamaica specimen; Kitty Emery and the Environmental Archaeology Program Laboratory at the Florida Museum of Natural History for facilitating access to guinea pig specimens from Finca Valencia, Puerto Rico ; William Keegan and Corinne Hofman for analysis of specimens from Giraudy, Saint Lucia; Daniel S. Sandweiss for permission to analyze the Lo Dem\u00e1s specimens housed at the Florida Museum of Natural History and site information; Ana Maria Boada for providing samples from El Venado, Colombia; and Martha Zierden and Elizabeth Reitz for providing the Charleston sample, site information and comments on the manuscript. Kuelap samples were selected and exported legally according to the Ministry of Culture of Peru Resoluci\u00f3n Viceministerial no. 095-2015-VMPCIC-MC (August 2015). We thank Susan Duser for assistance in creating Figs. 1A and 2. We acknowledge Peter Stahl for his review of the manuscript prior to publication. Funding for this research was provided to EM-S by the Department of Anatomy, University of Otago. Open access funding provided by Stockholm University.\u201dshould read:\u201cWe would like to thank Matthew Smith for providing the Green Castle, Jamaica specimen; Kitty Emery and the Environmental Archaeology Program Laboratory at the Florida Museum of Natural History for facilitating access to guinea pig specimens from Finca Valencia, Puerto Rico ; William Keegan and Corinne Hofman for analysis of specimens from Giraudy, Saint Lucia; Daniel S. Sandweiss for permission to analyze the Lo Dem\u00e1s specimens housed at the Florida Museum of Natural History and site information; Ana Maria Boada for providing samples from El Venado, Colombia; and Martha Zierden and Elizabeth Reitz for providing the Charleston sample, site information and comments on the manuscript. Kuelap samples were selected and exported legally according to the Ministry of Culture of Peru Resoluci\u00f3n Viceministerial no. 095-2015-VMPCIC-MC (August 2015). We thank Susan Duser for assistance in creating Figs. 1A and 2. We acknowledge Peter Stahl for his review of the manuscript prior to publication. Funding for this research was provided to EM-S by the Department of Anatomy, University of Otago. Open access funding provided by Stockholm University. We would like to thank Marceline Denis and C\u00e9cile Ansieau for providing the specimen from Mons, Belgium.\u201dAdditionally, there are typographical errors. In the legend of Figure\u00a02,\u201cThe routes depicted are purely hypothetical; people may have translocating guinea pigs using routes other than those depicted.\u201dshould read:\u201cThe routes depicted are purely hypothetical; people may have translocated guinea pigs using routes other than those depicted.\u201dIn the Author Contributions section,\u201cE.L., E.M.-S., S.d.F., M.J.L. conceived the study. E.L. carried out the laboratory work and analyses with assistance from C.C., S.dF., M.J.L., F.P., P.E., C.E., S.M.F., P.F.H., M.F.M.-P., J.L.G., E.R.R., M.D., A.S.U., G.A.P.L., J.M.T., A.D., K.M.M., C.LD., and C.Z. provided samples.\u201dshould read:\u201cE.L., E.M.-S., S.d.F., M.J.L. conceived the study. E.L. carried out the laboratory work and analyses with assistance from C.C.. S.dF., M.J.L., F.P., P.E., C.E., S.M.F., P.F.H., M.F.M.-P., J.L.G., E.R.R., M.D., A.S.U., G.A.P.L., J.M.T., A.D., K.M.M., C.LD., and C.Z. provided samples.\u201d"} +{"text": "The affiliation for Dr. Paniskaki was shown wrongly. The affiliation should appear as shown above. The article has been updated online.Volume 11, no. 5, e02243-20, 2020,"} +{"text": "Alloplasmic lines are a suitable model for studying molecular coevolution and interrelations between genetic systems of plant cells. Whole chloroplast (cp) and mitochondrial (mt) genome sequences were obtained by the MiSeq System (Illumina). Organelle DNA samples were prepared from a set of 12 alloplasmic barley lines with different cytoplasms of Hordeum vulgare ssp. spontaneum and H. vulgare ssp. vulgare, as well as from their paternal varieties. A bioinformatic approach for analysis of NGS data obtained on an organellar DNA mix has been developed and verified. A comparative study of Hordeum organelle genomes\u2019 variability and disposition of polymorphic loci was conducted. Eight types of chloroplast DNA and 5 types of mitochondrial DNA were distinguished for the barley sample set examined. These results were compared with the previous data of a restriction fragment length polymorphism (RFLP) study of organelle DNAs for the same material. Formerly established data about a field evaluation of alloplasmic barley lines were revised in the light of information about organelle genomes gained after NGS. Totally 17 polymorphic loci were found at exons of chloroplast genomes. Seven of the SNPs were located in the genes of the Ndh complex. The nonsynonymous changes of nucleotides were detected in the matK, rpoC1, ndhK, ndhG and infA genes. Some of the SNPs detected are very similar in codon position and in the type of amino acid substitution to the places where RNA editing can occur. Thus, these results outline new perspectives for the future study of nuclear-cytoplasmic interactions in alloplasmic lines. Barley is one of the most important cereals in the world, afterwheat and rice. The history of its cultivation stretches fromancient times . Peculiar distributionof different nuclear and cytoplasmic gene loci of barley acrosslocalities occurred together with the process of migration ofhumans . In parallel with the processof barley spreading from the centers of origin to differentclimatic zones, definite changes in nuclear and cytoplasmicgenes have happened. This led to change in the interactions ofthe nucleus and cytoplasm, the establishment of new nuclearcytoplasmicrelations.Chloroplasts and mitochondria are essential organelles inplant cells and play an important role in sustaining life. Thegenomes of organelles have a number of properties that makethem indispensable for studying in various areas of modernbiology: a large number of copies per cell; relatively conservativesequences; lack of recombination; maternal inheritance;coding the proteins for photosynthesis and respiration; endosymbioticorigin .The efficiency of photosynthesis (the cooperative workof chloroplast and nuclear genes) and the functioning of themitochondrial respiratory chain complexes basically determine the productivity of plants.Among the suitable models for study of nuclear-cytoplasmicinteractions are allo- and isoplasmic plant lines. Alloplasmiclines are usually created via hybridization when the nucleusfrom one plant (species or subspecies) are placed into thecytoplasmof another plant through substitution backcrossing.Evolutionarily established relations between nucleus andcytoplasm are disrupted at this case, and various consequenciescould arise as the result. There is the big set of data aboutdifferent effects of nuclear-cytoplasmic interactions. Wheatalloplasmic lines with the nucleus from Triticum aestivumand cytoplasm from different Aegilops and Triticum specieswere studied . Barley alloplasmiclines were also created and thoroughly studied . Different manifestationsof nuclear-cytoplasmic interactions were investigated withthe help of the alloplasmic lines collections: the influence ofplasmon on morphogenesis, photosynthesis and respiration,fertility, different stress conditions, transmission and recombinationof nuclear genes of plants .NGS of the whole chloroplast (cp) and mitochondrial (mt)genomes from different matrices allows to explore large number of samples simultaneously,to obtain qualitatively new comparative data about thevariability of cytoplasmic genomes . Especially the sequencing of pure organelleDNA templates \u2013 chloroplast or mitochondrial (or mixture oforganelle DNAs), gained after organelle lysis appears to bethe most promising for organelle genome studies. In this casenumerous genomic and organelle DNA-like sequences fromnucleus are drawn away from analysis facilitating the processof organelle genomes assembly.Complete chloroplast and mitochondrial genome sequencesare essential for realizing and reshaping the phylogeneticrelationships between closely related taxa and for improvingour understanding of the evolution of plant species .The comparative study of the plastid genomes variability inalloplasmic barley lines (differing in origin of the cytoplasmdonor) and their euplasmic analogues were performed.Study material. Three barley varieties Vezha, Roland, Visitas well as twelve alloplasmic lines created and maintainedin the Lab of Cytoplasmic Inheritance were used for organelle DNAisolation (Table 1).We explored alloplasmic barley lines with cytoplasm ofH. spontaneum and H. vulgare, as unfortunately we lack theoriginal seeds of H. spontaneum and H. vulgare donors ofcytoplasm . This plant material was createdin 1990th and then maintained by self pollinating.The maternal inheritance of organelle genomes is welldocumented in angiosperms, and considered as one of the lawsof cytoplasmic inheritance , though very seldomoccasional paternal transmission can occur . We considered the plasmon of definite alloplasmicline is equivalent to the original plasmon of correspondingwild H. spontaneum, H. vulgare. Moreover, one of the recentstudies of alloplasmic lines in Triticum-Aegilops complexdemonstrated the stability of organellar DNA characteristicsbetween native euplasmic plants and alloplasmic line, indicatinggenerally the usefulness of organellar genome in tracingthe maternal lineage of species .The whole sequences of H. vulgare chloroplast and mitochondrial genomes accessible in NCBI nucleotide database(GenBank) were used as references for assembly of new barleyorganelle genomes.DNA extraction. Organelles were extracted from 7 daysseedlings. The fraction of organelles was obtained by differentialcentrifugation . Chloroplastand mitochondrial DNA were obtained by lysis of isolatedorganelles with subsequent phenol-chloroform deproteinization.This approach allowed simultaneous sequencing of bothgenomes from each sample. The quality and concentration ofDNA was evaluated after 0.8 % agarose gel electrophoresisand at NanoDrop 8000 spectophotometer (Thermo FisherScientific).NGS. The NGS was perfomed on the MiSeq System , library preparation kitNexteraXT, MiSeq Reagent Kit v3, read lengths 300 bp.NGS data processing. The raw data were exported forthe primary analysis. The algorithm of sequencing data processingincluded the following steps: trimming of raw reads; aligning reads to the\u201cdouble\u201d reference, containing full sequences of chloroplastand mitochondrial barley genomes ; obtaining mappingstatistics ; alignment visualization ; generating VCF files ;filtering VCF files . Thealgorithm was tested on artificial Illumina reads synthesizedusing the ART program. Ultimately, VCF files containingall polymorphic loci of the chloroplast and mitochondrialgenomes were obtained .Comparative analysis of cp genomes. The VCF filesfor cp genomes of all studied samples as well as accessiblecomplete cp genome sequences of H. vulgare ssp. vulgare(NC_008590) and H. vulgare ssp. spontaneum taken from the NCBI GenBank database wereinvolved in whole-genome comparison analysis. To visuallydisplay the phylogenetic relationships between the studiedsamples and divide them into groups by the types of chloroplastgenomes, the maximum parsimony-cladogram wasconstructed on the base of all founded SNPs and INDELs.Complete chloroplast genome sequences of H. jubatum(KM974741) and H. bulbosum (KY636105) available in NCBIGenBank acted as outgroups. The cladogram was built in Excel(Version 14.0.6112.5000) with searching for homologousregions in the outgroup genomes using the SnapGene V.4.3.10.15 chloroplast and 15 mitochondrial genome sequences wereobtained after NGS of organelle DNAsamples . Bioinformatics\u2019approaches have been optimized for the processing of the\u201craw\u201d data after sequencing the mixture of cp and mtDNA. The comparative analysis of the obtained sequences as wellas available in NCBI nucleotide database (GenBank) wascarried out, that promoted the assessment of the total levelof sequence variation between samples of the same species,defined the regions, where changes more often occur.Generally, 103 polymorphic loci of cpDNA were revealedafter comparison analysis of 15 obtained new full organellesequences and 4 sequences from GenBank . Among them 78 differences for the alloplasmic linesand barley paternal varieties were detected: 56 SNP ),14 SSR loci and 8 indels.The cladogram for the complete chloroplast genomes ofbarley was constructed on the base of polymorphic loci found,except for the SSR regions . It displays thediversity of chloroplast genomes of H. vulgare and H. spontaneum,which allows to subdivide the plasmotypes in thestudy set of barley (see below Table 2).20 loci of mtDNA variability were identified. The level ofsequence variation was much lower compared to chloroplastDNA. Only two types of changes were detected \u2013 point nucleotidesubstitutions (19) and insertion (1). All the indels and themost significant SNP were checked by Sanger sequencing toverify the assembly of both genomes.Qualitatively new data about the variability of Hordeumorganelle genomes and disposition of polymorphic loci wereobtained after NGS. It turned out to be higher than describedin earlier reports based on RFLP data or SSR analysis ofrelatively few loci .Differentiation of the alloplasmic lines collectionaccording various molecular methodsAs a result of NGS study, eight types of chloroplast DNAand five types of mitochondrial DNA were distinguished forthe examined barley sample set (Table 2). We were able tohighlight eight plasmotypes totally.Earlier in 1984 the same set of cytoplasms as well as someothers: W1, W3, W4, W5, W7, W8, W9, W10, Atlas, Himalaya,L1, L2 \u2013 were studied via restriction of cpDNA with 4 endonucleases BamHI, BclI, EcoRI, HindIII . Five different chloroplast RFLP patterns weredetected. Afterwards mtDNA endonuclease digestion wasperformed for 12 alloplasmic lines with the above mentionedcytoplasmsand nucleus from barley variety Vezha.Four groups of mtDNA types were detected . Combining these results, 9 specific plasmotypes weredistinguished (Table 3).NGS data for chloroplast genome (this work) and earlierobtained RFLP data were compared.RFLP analysis having quite low resolution was not able toshow all the differences between samples. So, we expectedthat sequencing of full chloroplast and mitochondrial genomesof alloplasmic lines will shed light on the organelle genomevariability of this collection.Specific motifs for BamHI, BclI, EcoRI, HindIII endonucleaseswere determined in obtained full chloroplast genomes(SnapGene V.4.3.10). Despite many variability positions betweensamples detected by NGS , they mainlydidn\u2019t affect the enzyme cutting sites (c. s.). All samples bearthe same endonuclease digestion points for BamHI (54 c. s.),BclI (53 c. s.), EcoRI (97 c. s.), HindIII (40 c. s.). Just onlyG33315A substitution led to appearance the new cutting sitefor BclI in W1, W3, W4, W8 and Vezha cytoplasm . All together they bear 54 BclI sites.The Roland (W9) appeared to be especially unique, becauseonly this line had four new SNP: A1888G (created the newdigestion site for HindII ), T25067C, T79838G and T79839A (that promote the emergence of two new EcoRI cutting points).Thus Roland (W9) bears 41 HindIII and 99 EcoRI cleavagepoints.We tried to collate the types of cytoplasms obtained bytwo different methodological approaches \u2013 RFLP and NGSsequencing .Roland (Atlas) and Roland refer to the sameplasmotype according to RFLP data, but NGS differentiated it.According to Clegg , W3 and W4 belongto different RFLP because of different cpDNA types and onecommon mitochondrial. However, the NGS study combinedthem in one group, with one exeption \u2013 Vizit (W3). Note aninteresting fact \u2013 W3 and W4 lines originated from one localityAtlit at Israel and they are most likely closer genetically thanother lines studied. Sequencing data put alloplasmic lines withW3 and W4 cytoplasm at one subcluster. So, Vezha (W3),Roland (W3), Roland (W4), Vezha (W4) are identical for allpolymorphic loci and Vizit (W3) is very similar to other alloplasmiclines with W3 cytoplasm, bearing variability onlyat 7 polymorphic loci.Alloplasmic lines with W8 cytoplasm formed separategroup according to both methods.Roland (W9) line was placed into the special RFLP group;according to NGS data, this line has more than 20 specificSNP, thus it appears to be remote from all other lines studied.SNP detected at chloroplast genome sequences,their possible importance for plantsOnly single nucleotide substitutions were revealed at exons ofchloroplast genes, 12 of them were synonymous: rpoA, rpoC1,rpoC2, ndhA, ndhD, ndhG, ndhH, ndhK, atpA, psaA genes.The 5 nonsynonymous changes of nucleotides were detectedin matK, rpoC1, ndhK, ndhG and infA genes (Table 4).Some of SNP detected are very similar to the places where RNA editing can occur. Editing usually appearedto be C-U replacement at the mRNA level, it corrects the\u201cwrong\u201d nucleotide at the DNA level. It leads to restorationof phylogenetically conservative amino acid sequences of theproteins .Editing is the important posttranscriptional control of thegene expression. It is necessary for plastids functioning andplants survival . Nucleotide substitutionsin matK 2634 \u0421 > T , ndhK 40894 C > T(p.Lys233Asn), infA 76884 G > A (p.Ser87Leu), ndhG111390 C > T (p.Gly16Glu), ndhA exon2 112780 A > G(p.Gly213=), ndhA exon1 114148 G > A (p.Pro101=), ndhAexon1 114340 C > T (p.Leu37=) possibly mark positionswhere editing could take place.According to Table 4, SNP at cpDNA 76884 nucleotideposition resulted in amino acid substitution p.Ser87Leu at infAgene for lines Hordeum vulgare subsp. spontaneum with W3and W4 cytoplasm. infA is the factor 1 of translation initiation(IF1) encoded in chloroplast. It is highly conserved anduniversal in all living organisms .Remarkably we found polymorphic loci at infA gene, position76884 G > A of cpDNA. This SNP occurred at the secondposition of codon, usual position for editing . The barley with cytoplasms W3, W4, and W1bear A (or T at opposite DNA strand) and they needn\u2019t correctionC > T at the RNA level (editing), but all the other samplesstudied possess C and it can be corrected by editing machinery.This substitution will lead to Ser>Leu change \u2013 most commonconversion during editing . Somefurther work to support this idea and to determine functionalpeculiarities of this event is needed.About half of SNP (7 out of 17) are located at the genes ofNADH complex. Chloroplast DNA of barley encodes 11 Ndhgenes. Of note that these genes are quite variable in differenttaxons and still remain between the relatively few numberof genes retained at cpDNA of higher plants in comparisonwith genome of prokaryotic Cyanobacteria ancestor. Theyhave been lost in Gnetales, pines, Erodium species, someparasitic plants, endowing their characteristic cpDNA features. Nevertheless, most landphotosynthetic plants contain these genes. It is considered,that they are important for adaptation of plants to photosynthesis. Ndh complexfunction is necessary to optimize photophosphorylation ratesunder different stress conditions .Nearly 50 % of editing sites of flowering plants concentrateat the ndh group of genes . We foundloci of variability at five of them. Possibly nucleotide substitutionC > T at 111390 position of cpDNA resulted in aminoacid change Gly16Glu, can be the place of editing event whichneeds future verification.The productivity characters of substituted barley lines withfive different nuclear genomes and six plasmotypes were thoroughlytested in field conditions for several years . The direct correlation between productivity and differencesin the structure of organelle genomes was not found.The effects of cytoplasm substitution on the economicallyvaluable traits of plants varied greatly depending on nuclear genome, significant impact for various traits was revealed fordefinite nuclear-cytoplasmic combinations. Nevertheless, twogroups of cytoplasms with minimal \u2013 W4, W8, and highestinfluence on productivity \u2013 A, L1, W3, W5 were defined onthe basis of comparative analysis.We have got detailed information about sequences of barleyorganelle genomes of set of alloplasmic lines. At present wecannot precisely foresee which cytoplasm type gives definitephenotypic effect. The results prove that interaction of definitenucleus with specific organelle genome in every case can beunique. Nevertheless, each line was marked and its peculiarfeatures were defined. It represents the new type of startingmaterial for prospective studies in breeding and moleculargenetics in Poaceae.Furthermore, alloplasmic lines appeared to be the promisingmaterial for the study of molecular coevolution betweengenetic systems of plant cell. If editing really occurs atsome loci of organelle genes of definite barley cytoplasmsit needs special transfactors, at least PLS-type PPR proteins(encoded in nucleus). These proteins are highly specificfor their RNA targets. If we combine in alloplasmic linescpDNA which needs editing and nucleus where transfactorfor this event is not encoded, how could plants overcomethis inconsistency? Another case \u2013 the cytoplasm loci needno editing, but transfactor is encoded in nucleus. Amazingly,phylogenetic comparison of editing sites and correspondingPPR proteins leads to the very interesting fact: if conversionC to T at the DNA level takes place, no need in editing existsand PPR protein can gradually disappear from the nucleus ofthis taxon. Moreover, as revealed for DOT4 PPR protein \u2013 theloss of editing target site through C to T conversion allowedDOT4 in Poaceae to adapt for new function. Also some caseswere described where the target sequences for editing exist,but no corresponding PPR is encoded by nucleus .Thus, the field for further studies of nuclear-cytoplasmic cooperationis quite large. Possibly editing (PLS-PPRs) or otherprocesses and their players both from nucleus and cytoplasmare involved, that bring us to discovery of fine mechanismsof different cell genetic systems interaction.The authors declare no conflict of interest.Batura F.N., Davydenko O.G., Kadyrov M.A. The substitution of cytoplasmin barley varieties and it breeding impact. 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Strategies for complete plastid genome sequencing.Mol. Ecol. Resour. 2017;17(5):858-868. DOI 10.1111/1755-0998.12626."} +{"text": "Scientific Reports 10.1038/s41598-020-58482-w, published online 31 January 2020Correction to: James W. Wilson was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:This project was conceived by R.C. and C.J.S. The experiments in this paper were designed and performed by A.S., J.W.W. and R.C. The HIF PHD inhibitors were generated by C.J.S. Data were analysed and interpreted by A.S., J.W.W. and R.C. The manuscript was prepared by A.S and J.W.W. and commented by R.C and C.J.S. All authors have read and approved the final copy of the manuscript."} +{"text": "Dear Editor, To date, there are no effective and specific treatments available against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the medical protocols include isolation measures of the patients and treatment of symptoms. Instead of developing new compounds against SARS-CoV-2 that could take years to be approved, researchers have sought to redirect safety drugs already approved for other diseases. Controversially, a chasm has opened up between scientific information about drugs to coronavirus disease (COVID-19) outbreak and the speed that physicians need more information thereupon, thus entering in the use of medications that are more doubtful than certain. Moreover, if new compounds are discovered, geopolitical and economic characteristics will determine their use to communities. Therefore, it would be ideal to find a low-cost and accessible drug for COVID\u201019. In this context, the ivermectin emerges as a potential treatment option for SARS-CoV-2 infection to help\u2212 channels, leading to hyperpolarization and consequently blocking neurotransmission in neurons and myocytes, resulting in paralysis and death of the infesting organism . It cauary, 2005). Regardghi, 2020) includighi, 2020), HIV-1,ghi, 2020), yellowghi, 2020), Chikunghi, 2020) and Venghi, 2020) and Zikghi, 2020), respecin vitro, with a single dose able to control viral replication within 24-48 hours. Some authors proposed that the inhibition of NS in the early course of infection induced by ivermectin could attenuate the severity, duration and spread of the infection heterodimer-mediated nuclear import of viral proteins, which is a crucial transporter in nucleocytoplasmic shuttling (NS) of the SARS-CoV nucleocapsid protein and indispensable for viral replication and decin vitro, several clinical trial protocols have been registered in the ClinicalTrials.gov evaluating the effects of this drug in combination with others treatment protocols in the COVID-19 therapy. A prospective, multi-center, randomized, double-blind trial study enrolling 102 participants was designed to assess the efficacy and safety of ivermectin (600 \u03bcg/Kg or 1200 \u03bcg/Kg) for the treatment of initial infection with SARS-CoV2 in mild and moderate patients . Finallin vitro, the spread use of this drug become a panacea in South America, especially stimulated by a scientific denialism or even by the current chasm to a gold standard treatment for COVID-19. On May, ivermectin was included as a COVID-19 treatment in Peru and Bolivia and on June 2020, at least one municipality in Brazil had approved the use of ivermectin as a preventive drug for COVID-19 . in vitro evidence showed that ivermectin is able to control SARS-CoV-2 virus replication . MoreoAuthors thank FAPITEC-SE, CAPES and CNPq. This study is part of EpiSERGIPE project.No conflicts of interest, financial or otherwise, are declared by the authors.P.R.M.F, V.S.S, L.H, A.A.S.A and L.J.Q.J drafted manuscript; P.R.M.F, V.S.S, L.H, A.A.S.A and L.J.Q.J edited and revised the manuscript; P.R.M.F, V.S.S, L.H, A.A.S.A and L.J.Q.J approved the final version of manuscript."} +{"text": "Nature Communications 10.1038/s41467-018-08256-w, published online 21 January 2019.Correction to: The original version of this Article omitted from the author list the 8th author Isabelle M. Mansuy who is from the \u2018Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Z\u00fcrich, Institute for Neuroscience, Department of Health Science and Technology of ETH Z\u00fcrich, Irchel Campus Room Y55H66, Winterthurerstrasse 190, CH-8057, Z\u00fcrich, Switzerland\u2019.Consequently, the following was added to the Acknowledgements: \u2018and funding from University Z\u00fcrich, ETH Z\u00fcrich and the Swiss National Science Foundation (grant 31003A-135715) awarded to I.M.M.\u2019 The following text was added to the \u201cMethods\u201d section \u2018ZH150/11 given to I.M.M. and \u2018. The following text was added to the Author Contributions: \u2018B.J.S. and A.C. performed some experiments reported in this article while supervised by I.M.M\u2019. This has been corrected in both the PDF and HTML versions of the Article.B.J.S. disagrees with the addition of Isabelle Mansuy as an author."} +{"text": "Scientific Reports, 10.1038/s41598-021-81165-z, published online 22 January 2021.Correction to:In the original version of this Article, the author William W. Ja was incorrectly indexed. This error has now been corrected."} +{"text": "Festucacaprina complex from southern Africa that includes description and illustration of the new species F.drakensbergensis from the Drakensberg Mountain Centre of Floristic Endemism of South Africa and Lesotho. Festucadrakensbergensis can be differentiated from F.caprina s.l. by forming lax short tufts with extravaginally-branching tillers and lateral-tending cataphyllous shoots or rhizomes present, basal foliage reaching < \u00bd the length of the culms, with generally shorter leaves and shorter anthers, 0.8\u22121.6(\u22121.8) mm long. The species also differs from the overlooked species F.exaristata \u2013 currently known from two collections from Lesotho \u2212 by its fibrous basal sheaths, usually sharp, keel-like leaf blade midrib, drooping panicle with lightly to densely scabrous pendent panicle branches, longer lemmas, 4.5\u22125.8 mm long, with awns usually present, 0.5\u20133 mm long, ovary apices sparsely to densely hairy and anthers 0.8\u22121.6(\u22121.8) mm long. Taxonomic notes on the different taxa of the F.caprina complex in southern Africa are also provided, including images, key, and lectotypification of F.caprinavar.curvula. This research adds a further two endemic species (F.drakensbergensis and F.exaristata) and two endemic varieties (F.caprinavar.irrasa and F.caprinavar.macra) to the Drakensberg Mountain Centre of Floristic Endemism.We present taxonomic notes on the DMC) includes the only alpine region in mainland Africa south of Mount Kilimanjaro , totalling ca. 680 species (NLC) of Festuca s.s., ca. 600 species Link, Narduroides Rouy, Vulpia C.C.Gmel. and Wangenheimia Moench), and the Broad Leaf Clade (BLC), ca. 82 species , including Drymochloa Holub, Leucopoa Griseb., Lojaconoa Gand., Lolium , Patzkea G.H. Loos, Pseudobromus K. Schum. and Xanthochloa (Krivot.) Tzvelev.The genus species : the NarFestuca s.l. as present in the Flora of Southern Africa (FSA) region . Generic limits of Festuca s.l. are still being resolved, particularly in the BLC Darbysh.), F.africana (Hack.) Clayton (= Pseudobromussilvaticus K. Schum.), F.costata Nees, F.killickii Kenn.-O\u2019Byrne, F.longipes Stapf and F.scabra Vahl belong to the BLC. Although it generally holds true, not all NLC and BLC taxa have narrow and broad leaves, respectively, for example, F.vulpioides being placed in the NLC (Festucadracomontana H.P. Linder (predicted to be BLC), F.exaristata E.B. Alexeev (not accounted for by NLC) and our new species (predicted to be NLC) have not been tested. the BLC . Of the examined , F.caprFestuca s.l. is one of the prominent genera present in the montane-alpine ecotone and alpine sub-centre of the DMC and was considered to be a complex of species by F.claytonii E.B. Alexeev from Kenya and F.exaristata E.B. Alexeev from the DMC, and raised F.caprinavar.macra to species rank. F.caprina accepted in previous treatments were not upheld in their treatment because of \u201cthe variability in the species and leaf anatomy, which are constant throughout\u201d. Although Festuca for the FSA region , glabrous or scabrous ; ligules < 1 mm long ; collars non-auriculate ; blades narrow, 0.2\u20131.5 mm wide in diameter, involute ; panicles loose or contracted ; spikelets 2 to several flowered (vs. 1-flowered in F.africana), awns 0\u20135.5 mm long (vs. 10\u201320 mm long in F.africana).Taxa in the DMC area , followed by herbarium research at PRE, clear differences were noted between specimens that were treated under F.caprina by Festuca taxa in other parts of the World Describe and illustrate the new F.caprina present in the DMC and the overlooked species, F.exaristata.(ii) Provide taxonomic notes on the distinct varieties of F.caprina complex in the FSA region.(iii) Provide a revised key for the DMC between 1 Feb and 9 Mar 2020, with 42 specimens belonging to the F.caprina complex collected, which are deposited in the PRE, NU and US (pending export permits) herbaria , 24 Mar 1975, P.C.V. du Toit 698 (PRE0240733); KwaZulu-Natal: Sentinel Trail, ca. 1.2 km from the chain ladders, 28.740834S, 28.886806E, 2867 m alt., Afro-montane grassland grading into Afro-alpine grassland, damp soil, infrequently grazed, 6 Mar 2020, S.P. Sylvester et al. 3714 ; KwaZulu-Natal: Sani Pass area, below southwest facing cliffs to the southeast of Sani Mountain Lodge, 29.585365S, 29.290839E, 2866 m alt., short Afro-alpine grassland, frequently to heavily grazed, 26 Feb 2020, S.P. Sylvester et al. 3637 ; [KwaZulu-Natal?:] Probably from Mont-aux-Sources [Sentinel Peak?], E.A.C.L.E. Schelpe 1394A (PRE0024522).Taxon classificationPlantaePoalesPoaceaeNees, Fl. Afr. Austral. Ill. 443. 1841. Festuca nubigena subsp. caprina (Nees) St.-Yves, Rev. Bretonne Bot. Pure Appl. 2: 79. 1927.DD93F5FD-94F7-58D4-A874-531194B095E3South Africa. [Eastern Cape:] Table mountain, Queenstown Dev., Los-Tafelberg, 5000\u22126000 ft [1524\u22121829 m alt.], [1840], [flowering in December], D.F. Dr\u00e9ge s.n. ; syntype: South Africa. Plantes du Cap, D.F. Dr\u00e9ge 8.e.3920? (P (P00434764 [image!])).= Festucacostatavar.longiseta Nees, Fl. Afr. Austral. Ill. 1: 447. 1841. Type: South Africa. [Eastern Cape:] Stockenstrom Division, Katberg, , 1840, D.F. Dr\u00e9ge s.n. based, in part, on the basal sheaths being fibrous. However, all type or original material of F.caprina, including the lectotype of F.caprinavar.caprina designated by var.irrasa, which were obviously fibrous. The protologue mentions basal sheaths to be fibrous and, as such, irrasa, which was designated by caprina. If we treat F.caprinavar.caprina based on the K lectotype and isolectotype designated by caprina should be considered as having entire basal sheaths that do not split into fibres. Oddly, the inflorescences of all var. caprina specimens studied had a distinct butter-like smell upon the opening of specimen press papers, which then quickly dissipated. This odour was barely to sometimes slightly susceptible in specimens of F.caprinavar.macra or var. irrasa or F.drakensbergensis. It remains to be seen whether this character is diagnostic and what phytochemical compounds are involved.Festucacaprinavar.caprina is more common at lower elevations in the Drakensberg Mountain Centre , F.caprina var. caprina was rarely encountered, being found in only 13 plots from the Eastern Cape and Free State. The species was usually encountered in lower elevation Afro-montane transitioning to Afro-alpine grasslands at ca. 2500\u22122700 m alt. or exceptionally at higher elevations to 2981 m alt. in damper shaded sites, highlighting its very low frequency and commonality in the high-elevation xeric Afro-alpine zone of the DMC.n Centre and surrFestucacaprinavar.curvula is also herein lectotypified. In the protologue, caprina that was found in Los-Tafelberg of the Eastern Cape Province, near Queenstown. caprina and var. curvula \u2018a\u2019 and \u2018b\u2019, respectively, with the S-G-6704 right hand plant chosen as lectotype based on this matching the protologue information and being the only specimen sheet amongst the original material to be annotated with an \u2018a\u2019 and \u2018b\u2019 in Nees von Esenbeck\u2019s cursive handwriting. The right-hand plant annotated with \u2018b\u2019 fitted the protologue description of var. curvula, with Nees differentiating the variety based on its shorter height, curved blades and subsecund panicle branches with few purplish spikelets. One specimen amongst the original material, D.F. Dr\u00e9ge 8.e.3920? (P00434764), also had \u2018Curvula\u2019 written on the label but limited locality information aside from \u2018Plantes du Cap\u2019 and is here considered a syntype of var. curvula as it also fits the description given in the protologue. While the differentiating characters of F.caprinavar.curvula are also found in F.drakensbergensis, we deduce that var. curvula is a slight variation from the norm in F.caprina as neither the type specimens designated herein, nor any of the other original material from the type locality, can be attributed to F.drakensbergensis based on their lacking extravaginal branching and cataphyllous shoots as well as having entire lustrous basal sheaths.South Africa. Eastern Cape: Naudes Nek pass, near Rhodes, 30.764792S, 28.105164E, 2588 m alt., Afro-alpine tussock grassland, low rock outcrop, 13 Feb 2020, S.P. Sylvester et al. 3492 ; Free State: Witsieshoek, at beginning of Sentinel trail by parking lot, path-side, 28.733181S, 28.893296E, 2607 m alt., 5 Feb 2020, S.P. Sylvester et al. 3418 (US); Free State: Witsieshoek, Sentinel trail, along beginning of trail that leads to the chain ladders that take you up to Amphitheatre, path-side, 28.736207S, 28.894084E, 2693 m alt., 5 Feb 2020, S.P. Sylvester et al. 3416 (US); Free State: Golden Gate National Park, summit of Wodehouse Peak, 14 Jan 1975, R.P. Ellis 2383 (PRE0464133); KwaZulu-Natal: Amphitheatre, slopes near the Tugela waterfall, Afro-alpine grassland, 28.750810S, 28.888942E, 2981 m alt., 5 Feb 2020, S.P. Sylvester et al. 3409a (US); KwaZulu-Natal: Sentinel Trail, off the main trail at the top of an east facing gully ca. 1 km from the chain ladders, 28.743162S, 28.888205E, 2953 m alt., shaded Afro-montane grassland grading into Afro-alpine grassland, damp soil, rarely grazed, 6 Mar 2020, S.P. Sylvester et al. 3713 .Taxon classificationPlantaePoalesPoaceaeStapf, Fl. Cap. 7: 720. 1900.B82713AF-70DA-5358-80C9-FE653AF53E30South Africa. [Eastern Cape: Grahamstown], Howison Poort, Nov 1894, H.G. Flanagan s.n. by the obviously fibrous basal sheaths and usually short-hispid or long-scabrous (prickles hair-like) lemmas, paleas and rachillas. The character of lemma, palea and rachilla pubescence sometimes varies with hispid hairs sometimes only found at the apex of some lemmas in the inflorescence. The panicle branches and pedicels are also usually densely short-hispid or long-scabrous with hooks elongating to become almost hair-like, a character not seen in the other members of the F.caprina complex, although this character also appears to vary. The variation may be due to introgressive hybridisation or lateral gene transfer between taxa, which possibly occur frequently in grasses and var. irrasa had inflorescence characteristics of var. irrasa, but antrorsely scabrous abaxial leaf-blade surfaces like var.macra. Further work is needed to clarify the circumscription and taxonomic position of var. irrasa. Festucadrakensbergensis, described herein, also usually has fibrous basal sheaths and, although not as conspicuous as F.caprinavar.irrasa, can be readily distinguished based on its extravaginal tiller branching, presence of rhizomes and smaller anther size, amongst other characters. grasses . This coFestucacaprinavar.irrasa is endemic to the DMC of southern Africa, being found in Lesotho and the South African Eastern Cape and KwaZulu-Natal Provinces and possibly the Free State Province . The species appears to be more common in the KwaZulu-Natal Province. During our ecological plot-based study across the Afro-alpine DMC , F.caprina var. irrasa was only encountered as locally abundant ([0.5\u2013]5\u201335% of 2 m \u00d7 2 m plot cover) populations in the damper southern sites of the DMC, i.e. Sehlabathebe National Park (Lesotho) and Barclays Pass . The species was found in only 11 plots ranging from the lower elevation Afro-montane to Afro-alpine grassland transition at ca. 2250 m alt. to wet Afro-alpine tussock grasslands at ca. 2750 m alt.Lesotho. Sehlabathebe National Park, lower end of the Park on the border, 29.877593S, 29.086461E, 2606 m alt., wet Afro-alpine tussock grassland, soil damp, not grazed recently, 20 Feb 2020, S.P. Sylvester et al. 3542 ; Sehlabathebe National Park, lower end of the Park on the border, 29.876061S, 29.086150E, 2645 m alt., gravelly slopes below basalt rock escarpment with grasses intermixed with forbs, soil damp, burned and grazed recently, 20 Feb 2020, S.P. Sylvester et al. 3547 . South Africa. Eastern Cape: Bastervoetpad Pass area, ca. 12 km east of Mountain Shadow Hotel on Barclay Pass, 31.172568S, 27.964747E, 2259 m alt., Afro-montane transitioning to Afro-alpine grassland under moderately-heavy grazing, 14 Feb 2020, S.P. Sylvester et al. 3512 (US); KwaZulu-Natal: Giants Castle, 10,000 ft [3048 m alt.], 8 Jan 1915, R.E. Symons 352 (PRE0023182); KwaZulu-Natal: Weenen county, top of Griffins Hill, ca. 5000 ft [1524 m alt.], sedgy banks of streamlet in highland sourveld, fairly frequent, 29 Oct 1944, J.P.H. Acocks 10740 (PRE0023178).Taxon classificationPlantaePoalesPoaceaeStapf, Fl. Cap. 7: 720. 1900. Festuca macra (Stapf) E.B. Alexeev, Bot. Zhurn. (Moscow & Leningrad) 71(8): 1116. 1986.33F5A787-825A-5407-B4AB-EBE4EF42A792South Africa. [Kalahari Region: Orange Free State:] Wittebergen, near Harrismith, Comm. O. MacOwan, Feb 1877, Buchanan 262 (holotype: K (K000345247 [image!]); isotype: PRE! fragm. ex K).macra to species level and differentiated it from F.caprina based on: a) sheaths of old leaves not falling apart into parallel thin threads into parallel thin threads in F.caprina, although this is now considered erroneous; see comments under F.caprina above); b) leaf blades more or less glaucous (vs. green in F.caprina); c) abaxial leaf-blade surfaces scabrous (vs. smooth or scaberulous in F.caprina); d) adaxial leaf-blade surfaces shortly hairy (vs. scabrous or shortly hairy in F.caprina); e) lemmas 4.5\u22125 mm long (vs. 5\u22127[9] mm long in F.caprina); f) awns 1.5\u22123.5 mm long (vs. [0.5]1\u22124 m long in F.caprina); g) anthers 1.6\u22122.2 mm long (vs. [2\u2212]2.5\u22124 mm long in F.caprina); h) spikelets straw-coloured-violet . However, only the holotype of F.caprinavar.macra was seen by Alexeev, as well as original material (from which a lectotype was selected) and a limited number of other specimens of F.caprinavar.caprina at the K herbarium.F.caprinavar.caprina and var. macra during extensive fieldwork in the DMC and herbarium study at PRE, it became apparent that the above-mentioned differentiating characters overlap. Both F.caprinavar.caprina and F.caprinavar.macra share most characteristics, such as intravaginal tillers forming dense, often large, tussocks, with entire, often lustrous, basal sheaths, narrow involute blades and similar inflorescence and spikelet morphology, with anthers usually > 2 mm long. The F.caprinavar.macra holotype is on the shorter side with regards most inflorescence characters when compared with F.caprinavar.caprina, with shorter spikelets, lemmas, awns and anthers according to the protologue. Nevertheless, most of these characters have also been found in specimens of F.caprinavar.caprina, with variability in lengths of the spikelet parts possibly being related to ecological conditions, including seasonal variations in rainfall . The anther length of 1.6 mm, mentioned in the protologue for F.macra . Indumentum of the adaxial leaf-blade surface was also found to vary between scabrous, long-scabrous with prickles becoming elongated and hair-like and shortly hispid in all the taxa of the F.caprina complex from southern Africa, with this character seen to have no diagnostic value.Upon study of numerous specimens that belong to F.macra : table 2Festucacaprinavar.macra was not included in the treatment of southern African grasses by F.caprina stating that the species was too variable. Nevertheless, we consider F.caprinavar.macra to be distinct from var. caprina based on the character of notably antrorsely scabrous abaxial leaf-blade surfaces that is not known outside of the DMC, with all other F.caprina specimens across their range being smooth or exceptionally scaberulous towards their apices. Specimens with notably scabrous leaf blades were also found to be geographically and ecologically distinct during fieldwork in the DMC, these being predominantly found in drier alpine areas of the DMC, while var. caprina was found in more mesic environments often at lower elevations in the montane belt.F.macra as a distinct species. While we currently disagree with this assessment, more exhaustive research may result in var. macra being raised to subspecies level, with certain characters still needing to be assessed such as lemma micromorphology, which has been proven to be taxonomically informative in Festuca by F.caprinavar.macra , with a total of 42 collections of the species being made. It is more palatable than Merxmuellera Conert species and so is less common in grazed areas . the DMC , being fFestucaobturbans St.-Yves and its allies F.gilbertiana Alexeev ex S.M. Phillipps and F.macrophylla A. Rich., described from Afro-alpine vegetation of Kenya or Ethiopia, also bear superficial similarity to F.caprinavar.macra in their intravaginally branched large tussocks with entire basal sheaths and fine, involute and usually scabrid leaf blades . Festucagilbertiana can be further differentiated by its smooth leaf blades, culms 30\u201335 cm tall, and sparse racemose inflorescence 60\u2013110(\u2013120+) cm tall, inflorescence usually a large loosely-contracted panicle in F.caprinavar.macra). Festucaobturbans can be further differentiated by having sheaths open to almost their base and ovary apices glabrous .f blades , b. Theser sizes , b. ThesF.caprinavar.macra, which was collected alongside them , such as tussock-forming habit with intravaginal branching and entire basal sheaths not splitting into fibres. However, they differed by their smooth abaxial leaf blade surfaces, placing them closer to F.caprinavar.caprina, unawned lemmas, which is unusual for both var. caprina and var. macra, and short spikelets with lowermost lemmas 4.5\u22125.8 mm long anthers measuring ca. 1.6\u22121.8 mm long, placing them closer to F.drakensbergensis. As F.drakensbergensis was also collected at the same localities , it is plausible that these could be hybrids between F.caprinavar.macra and F.drakensbergensis. More study, including further collections, is required to ascertain the identity of these specimens.Two specimens found near the Tiffindell Ski Resort of the Eastern Cape, South Africa and Bokong Nature Reserve, Lesotho , bore characteristics of Lesotho. AfriSki area, in valley adjoining and northwest of the valley of the AfriSki resort, on the north side of the A1 highway, 28.808394S, 28.708658E, 3104 m alt., dry upper slopes above valley, 27 Feb 2020, S.P. Sylvester et al. 3652 ; AfriSki resort, in valley just west of the resort centre, 28.822906S, 28.724602E, 3046 m alt., relatively undisturbed damp Afro-alpine grassland, 28 Feb 2020, S.P. Sylvester et al. 3663 ; Bokong Nature Reserve, ca. 350 m north from the information centre, 29.067203S, 28.421496E, 2972 m alt., Afro-alpine grassland dominated by Lachnagrostisbarbuligeravar.barbuligera with moderately-controlled grazing and burning, 2 Mar 2020, S.P. Sylvester et al. 3687b (US); S.P. Sylvester et al. 3687c (US); Matebeng Pass, below highest summit close to the pass, 29.870708S, 28.976534E, 3094 m alt., \u201cLesotho Highland Basalt Grassland\u201d with clear elements of \u201cDrakensberg Afro-alpine Heathland\u201d with Erica and Helichrysum shrubs dominating the landscape, 22 Feb 2020, S.P. Sylvester et al. 3576 (US); Matebeng Pass, below highest summit close to the pass, 29.868524S, 28.976439E, 3125 m alt., Afro-alpine vegetation with Ericaceous shrubs dominating the landscape, heavy grazing, 22 Feb 2020, S.P. Sylvester et al. 3580 (US); Matebeng Pass, below highest summit close to the pass, 29.873765S, 28.976929E, 2947 m alt., Afro-alpine vegetation with Ericaceous shrubs dominating the landscape, heavy grazing, 22 Feb 2020, S.P. Sylvester et al. 3588 ; Menoaneng Pass, on road between Rafolatsane and Thaba-Tseka, 29.427317S, 28.950617E, 3039 m alt., Afro-alpine grassland, windy ridge, grazed, 24 Feb 2020, S.P. Sylvester et al. 3601 (US); Sani Pass area, ca. 800 m east of Sani Mountain Lodge, 29.585198S, 29.292011E, 2896 m alt., short Afro-alpine grassland, frequently to heavily grazed, 25 Feb 2020, S.P. Sylvester et al. 3619 ; S.P. Sylvester et al. 3620 (US); Sehlabathebe National Park, lower end of the Park on the border, 29.859882S, 29.095598E, 2779 m alt., wet Afro-alpine tussock grassland, soil damp, under dripping crag, heavily grazed, close to livestock paths, 19 Feb 2020, S.P. Sylvester et al. 3523 ; Sehlabathebe National Park, lower end of the Park on the border, 29.860180S, 29.095586E, 2733 m alt., wet Afro-alpine tussock grassland, soil damp, under dripping crag, heavily grazed, close to livestock paths, 19 Feb 2020, S.P. Sylvester et al. 3538 . South Africa. Eastern Cape: between Carlisleshoekspruit Pass and Tiffindell Ski Area, 30.6852485S, 27.963802E, 2565 m alt., Afro-alpine grassland, 10 Feb 2020, S.P. Sylvester et al. 3428a ; Eastern Cape: between Carlisleshoekspruit Pass and Tiffindell Ski Area, 30.6852485S, 27.963802E, 2565 m alt., Afro-alpine grassland, 10 Feb 2020, S.P. Sylvester et al. 3428b ; Eastern Cape: Tiffindell Ski Area, 30.649239S, 27.928720E, 2845 m alt., Afro-alpine grassland, 10 Feb 2020, S.P. Sylvester et al. 3446 ; Eastern Cape: Tiffindell Ski Area, 30.676006S, 27.958567E, 2527 m alt., Afro-alpine tussock grassland, 12 Feb 2020, S.P. Sylvester et al. 3480 ; Eastern Cape: Tiffindell Ski Area, Ben Macdhui summit, 30.648172S, 27.935507E, 2998 m alt., Afro-alpine grassland, 11 Feb 2020, S.P. Sylvester et al. 3462b ; Eastern Cape: Tiffindell Ski Area, next to ski lift, 30.651034S, 27.925149E, 2778 m alt., Afro-alpine grassland, annually burnt, appears to be seeded with exotic species, 11 Feb 2020, S.P. Sylvester et al. 3463 ; KwaZulu-Natal: Amphitheatre, slopes near the Tugela waterfall, 28.754008S, 28.893853E, 2983 m alt., Afro-alpine grassland, 5 Feb 2020, S.P. Sylvester et al. 3403 ; KwaZulu-Natal: Amphitheatre, slopes near the Tugela waterfall, 28.753989S, 28.893563E, 2979 m alt., Afro-alpine grassland, 5 Feb 2020, S.P. Sylvester et al. 3406 (US); KwaZulu-Natal: Amphitheatre, slopes near the Tugela waterfall, 28.750810S, 28.888942E, 2981 m alt., Afro-alpine grassland, 5 Feb 2020, S.P. Sylvester et al. 3409b (US).Taxon classificationPlantaePoalesPoaceaeE.B. Alexeev, Bot. Zhurn. (Moscow & Leningrad) 71(8): 1116. 1986.9F19FFA2-8871-5D06-8F2F-8B20EA3E6BA1[Lesotho] Basutoland. Above the Sani Pass, among stones, 9800 ft [2987 m alt.], 3 Feb 1959, M. McCallum Webster 483b (holotype: K (K000345250 [image!])).F.exaristata and did not cover all the habitats present. The holotype label states \u2018Above the Sani Pass\u2019 probably referring to the mountain slopes and ridge immediately above the Sani Pass, which were not explored by us. Our exploration largely focused on the valley bottom, which experienced very heavy grazing, with it being possible that the species may have been grazed out in these areas. As the species exhibits certain characters of both F.caprina s.l. and F.drakensbergensis, as well as other characters not found on any of these , there is also the possibility that the species is a hybrid which failed to survive into subsequent generations. However, the paratype, which was not seen by us, but was collected in 1977, 18 years after and ca. 130 km southwest of the type collection, raises doubt over this.This species was not included in the treatments to southern African grasses , nor in F.macra (= F.caprinavar.macra) and F.caprina in part by: a) leaf blade mid-vein blunt and rounded; b) panicle branches smooth; c) lemmas 4\u22124.2 mm long; d) lemmas unawned; e) ovary apex glabrous; f) anthers 1.5\u22121.8 mm long. It can be further differentiated from F.caprinavar.irrasa by the basal sheaths being entire, and from F.caprinavar.macra by the leaf blade abaxial surfaces being smooth. Furthermore, although not mentioned by F.caprina s.l. The species does bear some resemblance to F.drakensbergensis (see notes under F.drakensbergensis)."} +{"text": "Amphicteis, A.hwanghaiensissp. nov., is described based on material from the Yellow Sea. The new species is characterized by the possession of long, stout, golden paleae with blunt tips, digitiform rudimentary notopodia on the abdominal uncinigers, uncini with a subrostral process, and a narrow rectangular hump separating branchial groups. Amphicteisdalmatica was redescribed from type materials at the Australian Museum, Sydney, and the differences between A.dalmatica and A.hwanghaiensissp. nov. are discussed. A key to distinguish Amphicteis species described or reported in Western Pacific waters is provided.A new species of the ampharetid genus Amphicteis Grube, 1850 is one of the most widely distributed and species-rich genera of the family Ampharetidae to the rank of species, the genus Amphicteis encompasses a total of 33 valid species according to WoRMS from China. Amphicteis is characterized by the presence of a prostomium with paired longitudinal glandular ridges and transverse or oblique nuchal ridges, four pairs of cirriform branchiae usually arranged in two transverse rows, the presence of paleae, smooth buccal tentacles, 17 thoracic chaetigers with tuberculate ventral cirri on the notopodia, and 13\u201319 abdominal segments with uncinigerous pinnules and rudimentary notopodia , and examined and photographed using compound microscopes. For SEM examination, another paratype was dehydrated in an ethanol series, then critical-point dried, sputter coated with gold, and examined at the SEM Laboratory, AM. Photos using stereo and compound microscopes were also taken at the SEM Laboratory, AM. All photos were edited with Adobe Photoshop CC software.The type material of Taxon classificationAnimaliaTerebellidaAmpharetidaeGenusGrube, 18500F1B06FF-1903-527F-81CC-F788AFE13FCBAmphitritegunneri Sars, 1835Prostomium with middle lobes as paired longitudinal glandular ridges and nuchal organs as transverse or oblique nuchal ridges. Buccal tentacles usually smooth. Four pairs of cirriform branchiae usually arranged in two transverse rows. Notochaetae in segment II present and usually developed as strong paleae. Seventeen thoracic chaetigers from segment III with notopodia bearing tuberculate ventral cirri. Modi\ufb01ed notopodia and intermediate uncinigers absent. Fourteen thoracic uncinigers with uncini-bearing neuropodial tori from segment VI. Usually 15 abdominal uncinigers present. Abdominal uncinigers with rudimentary notopodia and uncini-bearing pinnules with digitiform or cirriform dorsal cirri. Usually one pair of anal cirri present, inserted laterally on pygidium. Thoracic and abdominal uncini with a single row of teeth.Taxon classificationAnimaliaTerebellidaAmpharetidae51D640FC-6489-59EF-BD70-6B7A5F1F6EF9http://zoobank.org/9AF8951F-61CE-406C-982F-9095865B8D04Type material. Yellow Sea, China , subtidal in mud, collected 28 November 2019. Holotype: MBM286623; Paratype: MBM286624, 1 specimen.Holotype Complete, length 27.8 mm, thoracic width 5.5 mm. Dorsum of thoracic segments and branchiae with red pigmentation , only five species have this type of paleae: A.mederi, A.midas , A.taurus Reuscher, Fiege & Imajima, 2015, A.ninonae Jirkov, 1985, and A.teresae Schiaparelli & Jirkov, 2016. According to A.dalmatica Hutchings & Rainer, 1979 and A.philippinarum Grube, 1878 also have short and poorly developed paleae. The latter species differs from A.hwanghaiensis sp. nov. by having foliose branchiae and uncini without a subrostral process, while A.hwanghaiensis sp. nov. only have cirriform branchiae and uncini with a subrostral process. To make clear the distinction between members of A.dalmatica and our new species, the type material of A.dalmatica was examined, redescribed, and compared with the new species (below).The presence of stout paleae with blunt tips is characteristic for Amphicteis species have paleae with fine filamentous tips; the difference between fine-tipped and stout-tipped paleae is easy to distinguish. According to A.mederi and A.hwanghaiensis sp. nov. is that A.mederi has abdominal pinnules with a cirriform dorsal cirrus, while the new species has a tuberculate dorsal cirrus; the thoracic and abdominal uncini of A.hwanghaiensis sp. nov. have five or six teeth in a single row over the basal prow while the uncini in A.mederi have six teeth of A.taurus and the shorter cephalic region of the new species . Amphicteishwanghaiensis sp. nov. has a lower lip with a narrow, distinct, and white middle transversal band which is absent in A.teresae. Uncini of A.hwanghaiensis sp. nov. have \ufb01ve or six teeth besides the subrostral tooth, while uncini of A.teresae usually have \ufb01ve. As for eyespots, which are absent in new species, Amphicteisteresae sp. n. that distinguishes it from the other related ones having blunt paleal chaetae is the presence of an eyespot\u201d. Furthermore, A.teresae is found in Antarctica.According to original description, Amphicteisninonae, recorded from Norwegian Sea and Arctic Seas, is most similar to the new species; however, members of this species are distinguished because, according to A.hwanghaiensis sp. nov. are golden. Amphicteishwanghaiensis sp. nov. also has a narrow rectangular hump between the branchial groups, while the area between the branchial groups of A.ninonae is flat and unmodified. A.ninonae seems to be restricted to the north and east coasts of Iceland.Amphicteis, A.glabra, A.gunneri, A.scaphobranchiata, and A.chinensis, have been recorded from Chinese seas, according to Amphicteis species with tips of paleae sharply tapering into fine \ufb01laments.Four species of Amphicteismalayensis Caullery, 1944 differ from those of A.hwanghaiensis sp. nov. by the possession of prostomial eyespots and a wide median gap between glandular ridges. Members of A.theeli Caullery, 1944 and A.quadridentata Caullery, 1944 have 14 and 16 abdominal uncinigers, respectively. The branchiae of individuals of A.spinosa Reuscher, Fiege & Imajima, 2015 have four rows of pointed protuberances, while branchiae are smooth among specimens belonging to our new species. Finally, specimens belonging to A.uncopalea Chamberlin, 1919, found in the North-western Paci\ufb01c, have well-developed paleae with curly and fine tips, and a distinct rounded lobe behind the paleae originating from segment III.Among the species from the Western Paci\ufb01c, specimens belonging to Taxon classificationAnimaliaTerebellidaAmpharetidaeHutchings & Rainier, 1979EE2CA4DF-4617-52B4-BA3E-A0954A891380AmphicteisdalmaticaType material. Australia, New South Wales, Pittwater, found in Zostera or Posidonia beds, 1\u20134 m deep. Holotype: AM W.8672, incomplete, 7 mm long, 2 mm wide anteriorly. Paratypes: AM W.8230, W.8242, W.8243, W.8249, W.8251, W.8252, W.8253, W.11667, W.11668, all incomplete; complete paratypes W.8243, W.8252, W.11667; W.8230 mounted for SEM examination.Types with dorsum of anterior segments speckled with pigmented spots, pigmentation decreasing posteriorly. Pigmentation still visible after decades of storage in alcohol, although paler than when originally described (compare our Fig. New South Wales, Australia.A.dalmatica are clearly distinct and differ from our new species in the following features. In A.dalmatica, the paleae are poorly developed, prostomial lateral lobes each have a cluster of eyespots basally, uncini have barely conspicuous subrostral process, and a distinct spotted pigmentation pattern is present on the dorsum of thoracic segments and branchiae. Members of Amphicteishwanghaiensis sp. nov. have well-developed paleae that are twice as long as the prostomium. Uncini of A.hwanghaiensis sp. nov. have a much larger subrostral process. Furthermore, the type locality of A.dalmatica is New South Wales, Australia, in seagrass beds.Members of"} +{"text": "Nature Communications 10.1038/s41467-023-38278-y, published online 6 May 2023Correction to: Climate and Environmental Change in the Mediterranean Basin\u2014Current Situation and Risks for the Future. First Mediterranean Assessment Report Ch. 1 .\u2019 The correct version states \u2018Lange, M.A. et al. Introduction. In: Climate and Environmental Change in the Mediterranean Basin\u2014Current Situation and Risks for the Future. First Mediterranean Assessment Report Union for the Mediterranean, Plan Bleu, UNEP/MAP, Marseille, France, 41\u201358, 10.5281/zenodo.7100592 (2020)\u2019. This has been corrected in both the PDF and HTML versions of the Article.The original version of this Article contained an error in reference 52, which incorrectly read \u2018Lange, M. A. et al. in"} +{"text": "ISME Communications 10.1038/s43705-022-00201-9, published online 16 December 2022Corrigendum to: Vulcanimicrobium alpinus (sic) gen. nov. sp. nov. along with higher-rank taxonomic names: the family , order , class (Eremiobacteriia), and phylum (Eremiobacterota). Vulcanimicrobium alpinum corrig. Yabe et al. 2023 was subsequently validated with a correction to the species name by Oren and G\u00f6ker [International Code of Nomenclature of Prokaryotes [Vulcanimicrobiaceae fam. nov., Vulcanimicrobiales ord. nov., Vulcanimicrobiia class. nov., and Vulcanimicrobiota phyl. nov. with following taxonomic descriptions.In the original version of the paper page 12-13), the authors described the bacterial name 2-13, theActinomycetota, which includes known photosynthetic lineages. However, the correct classification should have been Acidobacteriota.Furthermore, in the Introduction of the original paper , the authors inadvertently included The authors apologize for any confusion caused.Description ofVulcanimicrobiaceaefam. nov.Vulcanimicrobium, a bacterial genus; -aceae, ending to denote a family; N.L. fem. pl. n. Vulcanimicrobiaceae, the Vulcanimicrobium family)....(Vul.ca.ni.mi.cro.bi.o\u2019ta. N.L. neut. n. Candidatus Eremiobacteraeota\", \"Candidatus Eremiobacterota\" [Not validly published synonyms: \"cterota\" , 5\u20137.Vulcanimicrobium. Type genus is Vulcanimicrobium.The description is the same as for the genus"} +{"text": "Mycobacterium abscessus complex, a part of the nontuberculous mycobacteria (NTM) group, comprises three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. boletii,-M. abscessus subsp. abscessus was identified through partial sequencing of the rpoB gene and further analyzed by the GenBank international database. After maintaining the azithromycin for 6 months, the lesions resolved leaving scars (The ng scars . The gro"} +{"text": "Adv. Sci. 2019, 6, 180198210.1002/advs.201801982DOI: https://doi.org/10.1002/advs.201801982), has been retracted by agreement between the authors, the journal Editor\u2010in\u2010Chief Kirsten Severing, and Wiley\u2010VCH GmbH. The retraction has been agreed on following concerns raised by a third party and a subsequent investigation by the corresponding authors. Data depicted in Figure 4 and Figure 5 could not be reproduced in follow\u2010up experiments. Therefore, the conclusions associated with those figures in the article are considered invalid.The above article, published online on May 3, 2019, in Wiley Online Library (E.S.K. participated in the study design, performed measurements, analyzed the data, compiled the figures and participated in manuscript writing. A.d.C. and S.S. participated in the study design, research supervision, and manuscript writing. J.I.P. participated in the study design. M.K.L.H. participated in research supervision and manuscript revision. C.M. assisted with the experimental procedures and data collection. Adv. Sci. 2019, 6, 180198210.1002/advs.201801982DOI: https://doi.org/10.1002/advs.201801982), has been retracted by agreement between the authors, the journal Editor\u2010in\u2010Chief Kirsten Severing, and Wiley\u2010VCH GmbH. The retraction has been agreed on following concerns raised by a third party and a subsequent investigation by the corresponding authors. Data depicted in Figure 4 and Figure 5 could not be reproduced in follow\u2010up experiments. Therefore, the conclusions associated with those figures in the article are considered invalid.The above article, published online on May 3, 2019, in Wiley Online Library (E.S.K. participated in the study design, performed measurements, analyzed the data, compiled the figures and participated in manuscript writing. A.d.C. and S.S. participated in the study design, research supervision, and manuscript writing. J.I.P. participated in the study design. M.K.L.H. participated in research supervision and manuscript revision. C.M. assisted with the experimental procedures and data collection."} +{"text": "Systematic review and meta-analysis of screening tools for language disorder By So KKH and To CKS (2022). Front. Pediatr. 10:801220. doi: 10.3389/fped.2022.801220A Corrigendum on In the published article, the name of one of the authors was incorrectly spelled in the reference 87, the author name has been changed from Lagerbere D. to Lagerberg D. The corrected reference appears below.Acta Paediatrica. (2019) 108:1642\u20138. doi: 10.1111/apa.14790\u201d\u201cNayeb L, Lagerberg D, Westerlund M, Sarkadi A, Lucas S, Eriksson M. Modifying a language screening tool for three-year-old children identified severe language disorders six months earlier. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Necrotizing pneumonia in children: Chest computed tomography vs. lung ultrasound By Carrard J, Bacher S, Rochat-Guignard I, Knebel J-F, Alamo L, Meuwly J-Y and Tenisch E. (2022) Front. Pediatr. 10:898402. doi: 10.3389/fped.2022.898402An Erratum on An omission to the funding section of the original article was made in error. The following sentence has been added: \u201cOpen access funding was provided by the University of Lausanne\u201d.The original version of this article has been updated."} +{"text": "The development of new biomarkers for prediction and early detection of human diseases, as well as for monitoring the response to therapy is one of the most relevant areas of modern human genetics and genomics. Until recently, it was believed that the function of human Y chromosome genes was limited to determining sex and controlling spermatogenesis. Thanks to occurance of large databases of the genome-wide association study (GWAS), there has been a transition to the use of large samples for analyzing genetic changes in both normal and pathological conditions. This has made it possible to assess the association of mosaic aneuploidy of the Y chromosome in somatic cells with a shorter lifespan in men compared to women. Based on data from the UK Biobank, an association was found between mosaic loss of the Y chromosome (mLOY) in peripheral blood leukocytes and the age of men over 70, as well as a number of oncological, cardiac, metabolic, neurodegenerative, and psychiatric diseases. As a result, mLOY in peripheral blood cells has been considered a potential marker of biological age in men and as a marker of certain age-related diseases. Currently, numerous associations have been identified between mLOY and genes based on GWAS and transcriptomes in affected tissues. However, the exact cause of mLOY and the impact and consequences of this phenomenon at the whole organism level have not been established. In particular, it is unclear whether aneuploidy of the Y chromosome in blood cells may affect the development of pathologies that manifest in other organs, such as the brain in Alzheimer\u2019s disease, or whether it is a neutral biomarker of general genomic instability. This review examines the main pathologies and genetic factors associated with mLOY, as well as the hypotheses regarding their interplay. Special attention is given to recent studies on mLOY in brain cells in Alzheimer\u2019s disease. Y-chromosome aneuploidy in somatic cells that occurring withage was first identified 60 years ago by karyotyping bloodcells and was attributed to the commonage-related phenomenon of accumulation of post-zygoticgenetic aberrations of both sex chromosomes and autosomes,unrelated to diseases . Somewhatlater karyotyping of bone marrow cells from male patientswith acute myeloid leukemia, myelodysplastic syndrome(MDS), myeloproliferative disorders (MPD), and healthydonors was performed to evaluate the contribution of LOY tothe malignancy of the diseases .Although aneuploidy is characteristic of many types oftumors, the incidence and level of mLOY both in patients withhematological cancers and healthy donors depend on maleage and not on the malignancy of the disease and thereforemLOY cannot be considered a marker of a malignant clone. Asa consequence, scientists did not classify mLOY to be a vitalfactor for several decades, because women survive withoutthe Y chromosomeMore recently the hypothesis of the absence of a connectionbetween mLOY and diseases has been challenged in severalstudies that used the fluorescent in situ hybridization (FISH)method. It was established that the frequency of mLOY isincreased in various solid tumors ,autoimmune thyroiditis, hematological cancers , and primary biliary cirrhosis .In recent years, with the advent of next-generation sequencingmethods and large GWAS databases, including the UKBiobank, with detailed clinical descriptions of donors, it becamepossible to accurately estimate the frequency of mLOYthrough statistical analysis. It has been established that 40 %of men over 70 years lack the Y chromosome in more than5 % of peripheral immune blood cells, and that mLOY in peripheralblood is associated with an increased risk of all-causemortality .Over the past decade, stable associations were found betweenmLOY in the blood and various age-related diseases,including hematological and non-hematological types of cancer , where the frequency ofmLOY varies from 15 to 80 % , maculardegeneration , cardiovascular diseases , andneurodegenerative diseases . In addition, the impact of external factors suchas smoking and environmental pollution on mLOY levels inblood cells was revealed .Based on these results, it was hypothesized that thebiological significance of the Y chromosome goes beyonddefining sex and ensuring normal spermatogenesis, and itmay contribute to pathological processes, whose molecularmechanisms are yet to be studied. The majority of mLOYstudies in pathologies are related to cancer and Alzheimer\u2019sdisease, which we will examine in more detail.LOY in solid tumor cellsmLOY has been detected by FISH in various types of stomachcancer, where the frequency of mLOY varied 61\u201369 %, 33\u201336 % of casespancreatic cancer , and 23\u201334 % of cases of bladder cancer , and in 12.7 % of breast cancerin men . LOY in various types of renalcell carcinoma has been well studied using FISH, where thefrequency of LOY varies from 77 % in papillary renal cellcarcinoma to 39 % in the most common type \u2013 clear cell renalcell carcinoma .It has been suggested that aberrations of the Y chromosomemay be responsible for the higher incidence of clear cell renalcell carcinoma in men compared to women. Indeed, in additionto the previously known association of copy number variationsin autosomes and this disease, analysis of whole-genome dataand multiplex PCR have shown that LOY is detected in tumorcells of more than 30 % of male patients . Surprisingly, the frequency of LOY in prostate cancertumor samples was found to be very low. For example, in astudy involving of 2053 specimens from patients who underwentprostatectomy, only 12 cases of Y chromosome aneuploidywere detected . This low frequencyof LOY may be explained by the fact that mLOY reflects theoverall chromosomal instability of tumor cells, which is lowerin prostate cancer compared to many other types of cancer .Due to the prevalence of LOY in blood, it was expectedto detect an increased frequency of LOY in bone marrowsamples from patients with various hematological disorders.In the study of 237 patient samples, including those with MDS,MPN, acute myeloid leukemia, chronic myeloid leukemia,multiple myeloma, and lymphoma, LOY was detected in only10 % of cases .Unfortunately, the prognostic potential of LOY in tumorsis not entirely clear. In head and neck cancer, LOY in tumorcells may be an indicator of therapy resistance . In invasive urothelial carcinomas, LOY intumors was not associated with survival, increased risk ofrecurrence, or increased risk of progression . For example, in prostate cancer, no significant associationswere found between loss of the Y chromosome intumor cells and patient age, tumor stage, or risk of recurrence.However, it was significantly associated with a highGleason score, which is associated with a poor prognosis.In summary, the absence of the Y chromosome is a commonevent in tumors, but it significantly differs in frequency fordifferent types of cancer, and not enough data have yet beenaccumulated to understand the reasons for these differences.In other words, the presence and level of mLOY in tumorscannot yet be considered as a marker of malignancy or importantinformation for predicting treatment and recurrence.A study of a large cohort from the Uppsala LongitudinalStudy of Adult Men (ULSAM) database showed that menwith mLOY in blood had an increased risk of cancer diagnosisand mortality from various non-hematological types ofcancer . An analysis including data forall solid tumor cases submitted to the UK Biobank was alsoconducted, with results confirming an association betweenmLOY frequency and tumor presence .The association of mLOY in blood with the risk of cancer inother organs has been described in several independent studieson a smaller cohort, for example, an increased frequency ofmLOY compared to age norms was shown for prostate cancerand colorectal cancer .Loss of the Y chromosome in leukocytes can also act asa marker of a tumor clone in hematological diseases. Forexample, associations of mLOY with a worse prognosis inleukemias such as AML , chronic myeloidleukemia , and chronic lymphocyticleukemia . However, in the case of MDSthat has not progressed to AML, the presence of mLOY maybe a favorable factor for recovery .Another identified condition for a stable association with MDSand the ability to predict its course is the presence of mLOYin a very high proportion (more than 75 %) of blood cells.An attempt to narrow the search area to specific types ofcells in the case of MDS was undertaken in the work , where the ratio of the level of mLOY in CD34+cells associated with MDS and mLOY in CD3+ cells notassociated with MDS was analyzed. The results showed thatthe level of mLOY in both CD34+ and CD3+ cells were agedependentin men without hematological diseases, and inthe case of CD34+ cells, it was significantly higher in MDSpatients compared to elderly control men without hematologicalpathologies. These data indicate that the level of LOYin the blood has an age-related basis, but is also associatedwith MDS. In addition, the authors determined the thresholdlevel of LOY in CD34+ cells in peripheral blood to distinguishage-related changes from increased mLOY in MDS, whichwas 21.5 %.Interesting data on a Chinese cohort were obtained in a studyof mLOY in lung cancer, where it is a protective factor againstthe development of lung cancer, but only in non-smokingpatients , which is the only report on a possibleprotective factor of mLOY, and is difficult to interpret.Additionally, it is worth noting the results of data analysisfrom the UK Biobank, contradicting the above, whichconcluded that mLOY is primarily associated with age andsmoking, but not with common types of cancer . This conclusion was criticized, as the study used datanot only from leukocytes but also from buccal epithelial cells. Later, it was shown that the additionof buccal epithelial cell data to mLOY analysis negated theresult obtained for mLOY in leukocytes .Thus, despite some disagreements in the results of the studies,it could be concluded that mLOY in human blood has significantpotential as one of the biomarkers of malignant diseases,especially when the level of mosaicism is above 20 %.The results of cytological studies suggest that the loss of theY chromosome in somatic cells occurs during cell division.The most common theory is that mLOY is associated witha mechanism involving the formation of micronuclei withisolated Y chromosomes after improper chromosome segregationduring mitosis, followed by the destruction of themicronucleus through autophagy, leading to the appearanceof 45,X0 cells in older men . Age-related factors, such as telomereshortening and centromere dysfunction, may increase chromosomalsegregation errors. Compared to mosaic aneuploidy ofautosomes and the X chromosome, mLOY is a more frequentevent, presumably due to its overall high heterochromatinizedstatus and small size . Inaddition, the human Y chromosome is enriched in repetitivesequences, which may play a role in chromosome segregationerrors during mitosis .It remains unclear at what stage of human leukocyte differentiationthe loss of the Y chromosome occurs and theclone having a 45,X0 karyotype is formed. One hypothesis isrelated to primary loss of the Y chromosome in hematopoieticprecursors. This process can be associated with clonal hematopoiesisof indeterminate potential (CHIP), which is definedas the detection of somatic mutations in genes typically associatedwith myeloid neoplasms in individuals without signsof hematologic malignancy. CHIP occurs due to aging ofhematopoietic stem cells that have accumulated mutations,leading to proliferative advantage over their peers, and as aresult, to clonal expansion .CHIP is an age-related phenomenon, regularly observed inhealthy elderly individuals with a frequency of up to 10 % atthe age of 70, and CHIP is also associated with an increasedrisk of hematologic malignancies and cardiovascular disease. WhethermLOY is one of the manifestations associated with CHIP hasbeen considered in the work of V. Ljungstr\u00f6m et al. (2022),where the frequency of mutations and mLOY in monocytes of men aged 65\u201390 was analyzed. The results of the study indicatea frequent coexistence of mLOY and CHIP in monocytes.Another study also revealed the co-occurrence of LOY andCHIP in bone marrow cells obtained from patients referredfor clinical bone marrow examination . Itshould be noted that in the case of the monocyte study, casesof LOY without CHIP, and vice versa, were also detected.However, the sample size of both studies was very limited(24 and 73 participants), and the obtained result requiresconfirmation in further studies. It should also be taken intoaccount that CHIP is observed in 10 % of 70-year-old men,and mLOY \u2013 in 40 %.We should also note that mLOY stands out among aneuploidiesin leukocytes by a higher frequency of occurrencein compared to other chromosomes, and may apparently bea biomarker of overall chromosomal instability, which ischaracteristic of general aging of the organism and many humandiseases. However, the use of mLOY for diagnostic andprognostic purposes is premature due to the lack of precisemechanistic data on the nature of this phenomenon. It is alsoyet to be determined whether the observed level of mLOYdepends on de novo events or high clonality, and how bothpossible mechanisms are related to stages of different diseases.The human Y chromosome, according to the latest version of the human genomeassembly is over 62 million base pairs long .The Y chromosome consists of three main regions: the ends ofthe chromosome contain pseudoautosomal regions (PAR1 andPAR2) that are homologous to the ends of the X chromosome,and the remainder (about 95 %) is the male-specific region ofthe Y chromosome (MSY), which does not undergo recombination, resulting in the accumulationof repetitive sequences in the MSY.According to the T2T-Y assembly, the Y chromosomecontains 693 annotated genes and 888 transcripts, of which107 (493 transcripts) are protein-coding. In addition to all thegenes annotated in GRCh38-Y, the T2T-Y assembly contains110 genes, of which 42 are predicted to be protein-coding.Y genes constantly degrade, which may be due to the lack ofrecombination on this chromosome. The presence of a largenumber of repeats, in turn, contributes to chromosomal rearrangementsand intrachromosomal recombination . Unfortunately, with theadvent of the GWAS era, Y chromosome variants have notbeen included in most GWAS due to the lack of recombinationand high repeat content , making the Y chromosome much less characterizedin molecular genetic terms than other human chromosomes.To identify the molecular genetic factors underlying the occurrenceof mLOY in a certain proportion of men, GWAS datafor autosomes are primarily used. The first genetic associationdiscovered with mLOY was linked to a single nucleotidevariation rs2887399 near the TCL1A gene .The product of this gene, the TCL1A protein, is involved incarcinogenesis, mainly through chromosomal rearrangements. A strong association between rs2887399and mLOY has been replicated in subsequent studies on othercohorts . In total,over 150 genetic variants in autosomes associated with mLOYhave been found , including variants ingenes involved in the regulation of cell cycle , chromatin structureduring mitosis , and kinetochore structureand function .Associations with cancer susceptibility genes, as well assomatic tumor growth factors and anti-tumor therapy targets,have also been identified. Such genes include those encodingproteins involved in DNA damage response and in apoptotic processes. These associations were confirmed in Japaneseand European populations, collectively containing data forover 750,000 men , and these variantshave later been successfully used to predict mLOY usingpolygenic risk score estimates .The identified genetic variations in key cell cycle genesprovide evidence that cells without a Y chromosome mayavoid molecular processes that destroy aneuploid cells, resultingin their proliferation and accumulation in the tissues.Moreover, there are no genes on the Y chromosome associatedwith somatic cell survival or mitosis, so its absence shouldnot be associated with limitation on cell division . On the other hand, many of the most commonly observedmutations associated with LOY are linked to general genomicinstability. Indeed, based on data from a large-scale cohortGWAS, it has been shown that mosaicisms across autosomesare more common in men with LOY .Most of the mLOY-related genetic variants are often locatednear genes known as tumor growth encoding factors,targets for cancer treatment, or those that contribute to cancersusceptibility. This is one of the explanations for the associationbetween mLOY and non-hematological cancers and theidentified loci are associated not only with various types ofmale-specific cancers (prostate cancer and germ cell tumors),but also with gender-independent types of cancer ,as well as with an increased risk of developing specific nonhematologicaltypes of cancer in women . Based on theseresults, it can be concluded that mLOY reflects a certain commonautosomally determined state of the organism.In addition to elucidating the root cause of mLOY, the challengeof genetic research on this phenomenon is to identifythe consequences of mosaic absence of all genes on the sexchromosome in leukocytes in an elderly man. One hypothesisis that the loss of certain genes in connection with clonalabsence of the Y chromosome can be considered as a triggerof molecular and biological processes that lead to age-relatedpathologies. In particular, it can be assumed that the loss ofgenes in the PAR1 and PAR2 regions may affect the level ofexpression of these genes.One example is the CD99 gene, located in the PAR1 regionof the Y and X chromosomes, which is not subject toX-inactivation in women , which mayindicate the importance of its balanced expression. TheCD99 gene, most highly expressed in blood cells, encodesthe transmembrane glycoprotein CD99, playing an importantrole in the functioning of the immune system and affects the key properties of leukocytes . Indeed,CITESeq analysis uncovered a reduced surface expressionof CD99 in individual leukocytes lacking a Y chromosome,which may be indicative of a link between LOY and immunefunctions of leukocytes that is dependent on the homologousregions of sex chromosomes .Another Y chromosome gene that can directly affect thedevelopment of malignant tumors is KDM6C, located in theMSY region and encoding histone demethylase. KDM6C hasa functionally similar X-linked homolog, KDM6A, whosedeficiency is particularly associated with the progression ofclear cell renal cell carcinoma . Otherinteresting Y chromosome genes functionally correspondingto tumor suppressors are KDM5B and KDM5D (histonedemethylases), DDX3Y (RNA helicase), EIF1AY (translationinitiation factor), RPS4Y1 (ribosome subunit), ZFY (transcriptionfactor) .The development of omics technologies has also made itpossible to consider in more detail the potential additionalfunctions of Y chromosome genes. Thus, based on proteomicstudies, it was found that the DDX3Y gene, located in theMSY region of the Y chromosome, can modulate neuronaldifferentiation , and the Y chromosomehaplogroup may be a risk factor for prostate cancer . It has been discovered that SRY (theMSY region that determines sex) may be an oncogenic factor, and furthermore, SRY is involvedin the molecular genetic pathway associated with pulmonaryarterial hypertension .There are initial indications of a possible effect of mLOY onautosomal gene expression. In particular, increased expressionof the known oncogene TCL1A was detected based on singlecell transcript sequencing (scRNAseq) data. The product ofthis gene, the TCL1 protein, is a stimulator of cell proliferation. Tumors with mLOY show increasedexpression of genes involved in resistance to both radiationtherapy and platinum-based chemotherapy drugs , which partly explains the association of mLOYwith treatment prognosis.Thus, genetic studies suggest that mLOY is determined asa highly polygenic phenomenon. Unfortunately, it is difficultto trace from GWAS data whether single-nucleotide andstructural variations in the Y chromosome itself influence therisk of mLOY. In particular, it will be relevant for populationstudies to determine the relationship between Y chromosomehaplogroups and various mLOY indicators. Based on thegenetic factors identified through association analysis, itcan be concluded that mLOY is influenced by an increasein the frequency of errors during mitosis and a disruption ofchromosomal balance recognition and apoptotic regulation.Alzheimer\u2019s disease is a progressive and irreversible neurodegenerativedisorder of the central nervous system, responsiblefor approximately 70 % of all dementia cases. Mutations inthe PSEN1, PSEN2, and APP genes were found as the maincause of familial AD .Many variations in genes that are risk factors for sporadicAD are also known. Among these, the apolipopro-teinE4 (ApoE4) allele is the greatest genetic risk factor,with homozygous ApoE4 carriers having a 14-fold increasedsusceptibility to AD . Although theaverage lifespan of men is shorter than that of women, thisage-related fatal disease develops less frequently in men.Therefore, the influence of the male sex chromosome on ADpathogenesis was unexpected. However, the results of thefirst case-control study of mLOY in AD patients using theEuropean Alzheimer\u2019s Disease Initiative stage 1, ULSAM,and the Prospective Study of the Vasculature in UppsalaSeniors (PIVUS) database showed that mLOY is statisticallysignificantly 2.8 times more common in leukocytes of menwith AD compared to a control group without brain pathologies. These results were based onthe analysis of high-quality sequencing data from 606 bloodDNA samples from AD patients and 1005 control samples ofall ages. To minimize the influence of age component on bothAD and mLOY (risk), separate confirmation of the associationbetween AD and mLOY was obtained for two sub-sampleswith narrow age ranges: men aged 70\u201375 and 75\u201380 years. The identified association persistedeven after taking into account the influence of other agerelateddiseases , as well asunhealthy habits . Longitudinal studies,in which participants were tested several times at an intervalof about 10 years, allowed the evaluation of mLOY as a riskfactor for AD. Thus, during the observation period of ULSAMand PIVUS, 140 individual cases of AD were registered. Theresults of the data analysis for these individuals, adjusted forthe age of the patient at the moment of blood sampling andage-related diseases, showed that mLOY is a significant riskfactor for AD, increasing the likelihood of its diagnosis by6.8-foldSince the ApoE4 haplotype is one of the most importantrisk factors for the development of AD and currently the onlyconfirmed genetic factor that affects lifespan on multipleindependent samples , its contribution isincreasingly being evaluated in studies related to age-relateddiseases. It is known that the presence of the ApoE2/3/4 haplotypecan affect the phenotypic expression of other geneticvariants . In the case of mLOY, ithas been shown that, firstly, the ApoE2/3/4 haplotype doesnot affect the level of mLOY in leukocytes . Also, the assessment of the joint effect of ApoE4and mLOY gave a negative result, from which the authorsconcluded that the risk of developing AD from these factorsmanifests independentlyHowever, some studies suggest that an integrative effectof mLOY and genes related to the development of AD ispossible. Thus, the influence of the ApoE4 haplotype on thepresence of mLOY in dorsolateral prefrontal cortex cells wasrevealed , and in a study using neuronsobtained from induced pluripotent stem cells from a patientwith familial AD with a mutation in the PSEN1 gene, it wasdemonstrated that LOY enhances the toxic effects of A\u03b242,leading to impared neuron differentiation and premature celldeath . In addition, a statisticallysignificant correlation between mLOY and variation locatedin proximity to the SPON1 gene, which is associated with the severity of dementia, was demonstrated in the Japanesepopulation .An attempt to answer the key question of whether LOY isa cause or consequence of age-related diseases has also beenundertaken for Alzheimer\u2019s disease. Quantitative comparisonsof LOY frequency showed that the percentage of mLOY ishigher in leukocytes than in neurons ,and is also associated with age. Studies using cell lines haveshown that the absence of the Y chromosome is more commonlyobserved in fibroblasts than in neuron-like iPS cells.However, considering that LOY may depend on the proliferativecapacity of cells, microglia and oligodendrocyte precursorcells may be more prone to LOY accumulation than terminallydifferentiated neuronal cells.Based on scRNAseq data and single-nucleus RNA sequencingby , LOY enrichment was shownin microglia, as opposed to neurons, astrocytes, and oligodendrocytes,in non-demented patients significantly higher mLOYlevels in observed microglia in case of Alzheimer\u2019s disease.Comparative analysis of microglia in different brain regionsrevealed that in the somatosensory cortex of male AD patients21 % of microglia classified as LOY compared to 1.81 % incontrols, while in the entorhinal cortex, the frequency of LOYwas 32.7 % in patients and 3.27 % in controls. According tothe authors, the elevated level of LOY in the entorhinal cortexof AD patients is of particular interest because this part of thebrain is the first to be affected in AD .Thus, based on several studies, it is becoming increasinglyevident that the frequency of mLOY is elevated in AD andcancer, and is also a risk factor for these conditions .A dual pathway of development for certain triggers leading toeither cancer or AD has been noted in several works . Indeed, it has been shown thatmLOY in blood is a competing risk factor between the onsetof AD and solid cancers .Summing up these results, it could be concluded that mLOYin blood, being a male-specific risk factor for both AD andcancer, may at least partially explain why men on average liveshorter lives than women.Recent studies have provided the first insights into changesin gene expression in brain cells associated with mLOY. Analysis using a population sampleof differentially expressed genes in microglial cells with andwithout the Y chromosome revealed 193 genes with dysregulatedexpression upon Y chromosome loss, including genesinvolved in aging, basic glioma biology, and inflammation. Through the intersection of the listof autosomal genes with dysregulated expression influencedby mLOY in leukocytes and microglia, genes TMEM176B,S100Z, TMEM71, CD226, B2M, SCMH1, LITAF, and IL15,predominantly related to immune response and inflammation,were identified.For genes located in the PARs of the sex chromosomes, acorrelation was found between mLOY and the expression ofCD99, previously identified in leukocytes, supporting the hypothesisof a possible disruption in immune system functioningdirectly associated with Y chromosome loss. In addition tothe CD99 gene, dysregulation of the genes GTPBP6, IL3RA,SLC25A6, P2RY8, AKAP17A, DHRSX, and CSF2RA, locatedin the PAR1 region of the Y chromosome, was observed inmicroglia. In particular, the CSF2RA gene, which is involvedin a molecular pathway associated with neurodegeneration, isexpressed only in microglia and macrophages associated withthe brain. As this study was conducted by a single researchgroup, these findings require confirmation in independentstudies.The association of mLOY in brain cells with AD promptedinvestigations into the link between this phenomenon andpsychiatric disorders. Data have been obtained indicatingeither no association or weak association with schizophrenia, as well as strong association of mLOYwith suicidal tendencies, with blood mLOY levels beingalmost three times higher in the latter case. Interestingly, nochanges in mLOY levels were detected in the dorsolateralprefrontal cortex of postmortem brains of individuals whodied by suicide, but these data are limited in reliability due tothe small sample size .Numerous studies in large cohorts have shown that the LOY inblood cells is a significant risk factor for mortality and variousdiseases in men. From the accumulated data on associationsof mLOY with various pathologies, it becomes increasinglylikely that analysis of LOY may become a sensitive biomarkerfor AD, solid tumors, hematological malignancies, and overallgenomic instability. However, it should be kept in mind thatno study has provided direct evidence on how mLOY arises,how it affects cells, and what consequences it has. In termsof a predictive potential perspective, it is necessary to understandwhether mLOY is a barometer reflecting the presenceof pathologies or, conversely, whether mLOY arises de novoand participates in the pathogenesis. In this regard, there areseveral questions that need to be answered, such as whether thepathogenic effect of LOY manifests in untransformed bloodcells or in transformed clones in the case of hematologicalmalignancies.Another question that needs to be resolved is how LOY innormal blood cells can be linked to pathological processes inother organs, leading to tumors in other organs or neurodegenerationin the brain. Currently, the most attractive hypothesisis the immune surveillance hypothesis, explaining the mechanismsunderlying associations between LOY in blood cellsand enhanced neoplastic cell proliferation in tumors in otherparts of the body or the development of Alzheimer\u2019s disease.Comparisons of data for mLOY in different populations arelimited by a small number of studies to date and differencesin methods. Most of the obtained data are ethnically limitedand may not be confirmed in poorly represented populationsin databases, such as African or Middle Eastern populations.Based on two studies from the same research group, it can bepreliminarily concluded that the prevalence of mLOY in menis higher in European populations than in African populations. However, it should be noted thatsuch comparisons are currently limited.Despite the many questions that are likely to be activelyaddressed in connection with the popularity of this topic, it canalready be concluded that mLOY plays a role in determiningthe health of elderly men.The authors declare no conflict of interest.Agahozo M.C., Timmermans M.A.M., Sleddens H.F.B.M., Foekens R.,Trapman-Jansen A.M.A.C., Schr\u00f6der C.P., van Leeuwen-Stok E.,Martens J.W.M., Dinjens W.N.M., van Deurzen C.H.M. Loss ofY-chromosome during male breast carcinogenesis. Cancers. 2020;12(3):631. 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J. 2007;120(22):2002-2005.Zhou W., Machiela M.J., Freedman N.D., Rothman N., Malats N., DagnallC., Caporaso N., Teras L.T., Gaudet M.M., Gapstur S.M., StevensV.L., Jacobs K.B., Sampson J., Albanes D., Weinstein S., VirtamoJ., Berndt S., Hoover R.N., Black A., Silverman D., Figueroa J.,Garcia-Closas M., Real F.X., Earl J., Marenne G., Rodriguez-SantiagoB., Karagas M., Johnson A., Schwenn M., Wu X., Gu J., Ye Y.,Hutchinson A., Tucker M., Perez-Jurado L.A., Dean M., Yeager M.,Chanock S.J. Mosaic loss of chromosome Y is associated with commonvariation near TCL1A. Nat. Genet. 2016;48(5):563-568. DOI10.1038/ng.3545."} +{"text": "Sparasion, endoparasitoids of Tettigoniidae, occur in the Nearctic, Palearctic, Afrotropical and Oriental regions. It is absent in the Neotropics and Australasia. Of the thirteen species found in the Oriental region only a single species is from India.The genus\u00a0Sparasion bilahari species group and Sparasion manavati species group - are proposed for species from the Oriental region. Thirty-six species are described and illustrated of which twenty-four are new: Sparasion albopilosellus Cameron, 1906 (Pakistan); S. bhairavi Veenakumari, sp. n. (India); S. bhupali Veenakumari, sp. n. (India); S. bihagi Veenakumari, sp. n. (India); S. bilahari Veenakumari, sp. n. (India); S. cellularis Strand, 1913 (Taiwan); S. coconcus Kozlov and L\u00ea, 2000 (Vietnam); S. coeruleus Kieffer, 1905 (Sumatra); S. cullaris Kozlov and L\u00ea, 2000 (Vietnam); S. darbari Veenakumari, sp. n. (India); S. deepaki Veenakumari, sp. n. (India); S. domes Kozlov and L\u00ea, 2000 (Vietnam); S. elbakyanae Veenakumari, sp. n. (India); S. formosus Kieffer, 1910 (Taiwan); S. hindoli Veenakumari, sp. n. (India); S. kalyani Veenakumari, sp. n. (India); S. kanakangi Veenakumari, sp. n. (India); S. karivadana Veenakumari, sp. n. (India); S. lividus Johnson, Masner & Musetti, 2008 (Philippines); S. manavati Veenakumari, sp. n. (India); S. meghmalhari Veenakumari, sp. n. (India); S. micromerus Kozlov and L\u00ea, 2000 (Vietnam); S. pahadi Veenakumari, sp. n. (India); S. philippinensis Kieffer, 1913 (Philippines); S. ratnangi Veenakumari, sp. n. (India); S. rupavati Veenakumari, sp. n. (India); S. salagami Veenakumari, sp. n. (India); S. shulini Veenakumari, sp. n. (India); S. sinensis Walker, 1852 (China); S. sivaranjini Veenakumari, sp. n. (India); S. syamalangi Veenakumari, sp. n. (India); S. todi Veenakumari, sp. n. (India); S. travancoricus Mani and Sharma, 1981 (India); S. vanaspati Veenakumari, sp. n. (India); S. visvambari Veenakumari, sp. n. (India) and S. zeelafi Veenakumari, sp. n. (India). Keys to Oriental species of Sparasion are furnished. Intrasexual colour morphs among females of Sparasion is reported. Lectotype is designated for Sparasion cellularis Strand.Two new species groups - Sparasion. Previously described species of Oriental Sparasion are redescribed and illustrated. Keys are furnished for all Oriental species.Twenty-four new species are added to the Indian fauna of Hymenoptera, the most speciose order of insects constituting ten per cent of all known species on earth consists of three groups: aculeate wasps, sawflies, and parasitic Hymenoptera. Platygastroidea, the third largest of the parasitic hymenopteran superfamilies after Ichneumonoidea and Chalcidoidea, are found in almost all habitats except the polar regions. They are relatively more speciose in wet tropical and subtropical forests than in other habitats . The sheSparasion of the Oriental region. Our collections over many years from across India revealed the presence of a surprisingly rich and undocumented fauna of this genus. Of the thirteen species of Sparasion currently known from the Oriental region, only one is from India. The remaining are from Southeast Asia, with one each from Pakistan, China and Taiwan. Most were scantily described and poorly illustrated, and some specimens are in such poor condition that even the \u2018photographic catalogues of the primary types of the species are of limited use in their recognition\u2019 .The distribution maps of Oriental and Indian species were made using open source software DIVA-GIS based on topographic grids retrieved from the DIVA-GIS database . The new species described in this paper have been assigned Zoobank registration numbers and mentioned under the respective species."} +{"text": "The Lived Experience of Professional Identity; The World Around Me; Belonging; Me; and Learning and Qualifications. Descriptions of professional identity are broad, varied, rich and multi-layered however the literature is under theorised with current theories potentially inadequate to capture its complexity and make meaningful contributions to the allied health professions.Professional identity impacts the workforce at personal, interpersonal and profession levels however there is a lack of reviews of professional identity research across practising health professionals. To summarise professional identity research in the health professions literature and explore how professional identity is described a scoping review was conducted by searching Medline, Psycinfo, Embase, Scopus, CINAHL, and Business Source Complete using \u201cprofessional identity\u201d and related terms for 32 health professions. Empirical studies of professional identity in post-registration health professionals were examined with health profession, career stage, background to research, theoretical underpinnings and constructs of professional identity being extracted, charted and analysed using content analysis where relevant. From 9941 studies, 160 studies across 17 health professions were identified, with nursing and medicine most common. Twenty studies focussed on professional identity in the five years post-entry to the workforce and 56 studies did not state career stage. The most common background for the research was the impact of political, social and healthcare reforms and advances. Thirty five percent of studies (n\u2009=\u200957) stated the use of a theory or framework of identity, the most common being classified as social theories. Individual constructs of professional identity across the research were categorised into five themes\u2014 Professional identity impacts the workforce at personal, interpersonal and profession levels, yet our understanding of this phenomenon is still developing. In the health professions, literature reviews of professional identity involve single professions, are focussed on students or involve multidisciplinary teams and do not address the range of health professions or their specific issues post registration ; career stage; terminology and focus of the paper. In line with scoping review guidelines search parameters were formulated and Medline; Psycinfo; Embase; Scopus; CINAHL; Business Source Complete were searched on 5 April 2020 by MC. An example of search strategies used is described in \u201cAppendix Studies from the search of the six databases were downloaded into Endnote (X9) and exported to Covidence for screening and assessment. Duplicates were removed and remaining titles and abstracts were screened for eligibility against exclusion and inclusion criteria Table . EligiblHand searching of reference lists of final included studies did not reveal any further studies.Version 1808, 2019). All studies were sorted and counted with respect to study characteristics.To comprehensively explore descriptions of professional identity in the health professions literature to address the research questions, key information from the included research studies such as author, year and title data and so on were imported from Covidence to directly pre-populate the charting table. Information was noted and charted in a uniform and systematic way using Microsoft Excel were identified and theories classified. As described above, research into identity and professional identity originates from a range of traditions and encompasses multiple and varied paradigms and broad classification of theory can help with conceptualisations of these theories and their relationships. Three broad categories of identity theory; y Hauge, . Where aTo ensure the rigour of this part of the coding process, a small number of studies (n\u2009=\u200910) were randomly chosen for comparison coding early in the process by selecting every 15th study of an alphabetical list of studies included in the review. These studies were coded against final categories of identity frameworks by two of the other authors (CP and SA) and resulted in strong agreement between the three coders. In instances where no author could agree on the use of a theory this study was classified as having no overt theory or framework.constructs of professional identity described across all studies were identified and classified using conventional content analysis. , United Kingdom 26) and Australia (21) with the majority of studies focusing on the disciplines of nursing (59) and medicine (38) . Sub-themes included supporting the development and maintenance of professional identity generally (5) utilised qualitative methods, with the remaining using quantitative (20 or 12%) and mixed methods (9 or 6%) Table . A wide individual, social, and poststructural and critical. Combinations of theories and theories developed through the research were also categorised. As described above, the categories narrative, spanning all three main categories of the studies.Five major themes containing 37 categories of constructs of professional identify were determined from the health professions literature Table . Note thAs previously discussed, constructs of professional identity were not discrete but rather intertwined, reciprocal and changing dependent on the individual and circumstances Fig.\u00a0.Fig. 2ThThe Lived Experience of Professional Identity comprised three categories, Becoming from Performing, Knowing from Practising and Practising. Becoming from Performing was referred to in 83 or 52% of studies. This category reflects performative aspects of professional identity development with individuals described as learning to identify as health professionals through observation and role modelling which was consolidated through repetition, practice, feedback and validation, and a growing sense of confidence as a health professional. This was not always experienced in a positive way as \u201cthe inhibiting culture of nursing was perpetuated through socialisation processes\u201d , describes health professionals\u2019 experience with patients, clients, communities and students over years of practice giving meaning to and shaping professional identities.Witnessing the experiences of others through relationships (30) and Personal experiences impacting interactions with clients (7).Knowing from practising included two subcategories\u2014Practising was described as intrinsic to professional identity in 23 or 14% of studies and was\u00a0identified as a locus of professional identity in the health professions. Clinical practice was also described as important in the development of leadership and management identity, giving meaning to leadership and a contributing to maintenance of professional collective identity. Three subcategories of Practicing were identified in the literature as impacting professional identity development\u2014Philosophy of practice, Visibility of practice and Autonomy in practice.Role was identified as an important component of professional identity across a number of themes and was referenced specifically in 86 or 54% of studies.Workplace was described as contributing to professional identity in 62 or 39% or studies. Workplace is described as influencing professional identity by dictating practice of health professionals, through perceived inadequacy of workplace conditions and through changing role, changing work, changing work environment and changing practice. Workplace influences on professional identity described above capture influences of political, social and healthcare reforms and advances, however these influences were discussed specifically in 21 or 13% of studies.Professional hierarchies between professions and within professions was described as impacting professional identity in 44 studies. Between-profession power hierarchies described the medical profession at the top of the hierarchy with community midwifery and school nursing literature describing themselves as being low in the hierarchy of professions. Other hierarchies of health professions/specialties were described by academics and by complementary and alternative medicine practitioners who described themselves as professions on the periphery. Within-profession hierarchies were described in the literature in relation to seniority, further training, expanded practice, higher or different qualifications, type of work, place of work , prototypical behaviour in relation to the profession and married vs unmarried female doctors. These dynamics of hierarchy between and within professions were also noted as being important with respect to validation of value and competence of professionals. Hierarchies were noted to exist within an organisational context.ominant paradigms and discourses of health and practice with its impact on professional identity described in 44 studies. The biomedical model of healthcare was the paradigm most often cited (in 28 of 44 studies) as being the dominant in models of care influencing development of professional identity.Dnowledge claims was described as influencing professional identity development in 22 studies. This included the privileging of evidence-based knowledge over experience-based knowledge, and benchmarked, marketable and externally levied \u2018quality\u2019 criteria being valued over immeasurable dimensions of practice such as the relational and experiential aspects of healthcare.Khealth professional-client relationship was also discussed in 14 studies as a component of professional identity underpinning identities such \u2018expert\u2019 and \u2018fixer\u2019.The ocietal expectations of the health professions, were also identified as influencing professional identity formation in 13 or 8% of studies.SThe Group) as an important aspect of professional identity was identified in 52 or 33% of studies with group collective identity being seen as important in 15 studies. The profession in relation to other professions, was another aspect of collective professional identity in seven studies. \u201cThinking of oneself as a \u2026..\u201d and doing, being, becoming, belonging to a discipline were identified as important in nine and three studies respectively. Identification with the organisation was seen as an important aspect in professional identity in 12 studies.Group identification , undertaking more training or qualifications, as well expanded or specialist practice. Transition from clinician roles were also documented as influences\u2014from clinician to educator, from clinician to academic and from clinician to manager/leader. Changes in clinical professions or working in novel areas of practice were also identified as boundary crossing as were dual roles such as clinician-scientists and clinician-manager and working across multiple boundaries, all of which were identified as influencing professional identity. The creation or existence of boundary closure between professions or specialties to consolidate professional identity development was discussed in 17 studies.Boundaries in the professions were identified as influencing professional identity in 75 papers and described in two ways\u2014through BSelf as a component of professional identity was discussed in 38 (24%) studies. Self reflected the foundations of personal identity such as personal characteristics, values, feelings, as well as personal life with strong interrelationships between self, personal and professional identities described. Social work and nursing describe their professions as being intrinsic to self. Another aspect of self relating to professional identity described in nine studies The stories I tell about myself and described/included the dominant stories professionals tell about themselves on the basis of their lived experience in the world. These stories, through a reflexive practice, were described as providing opportunities for identification and deconstruction of discourses at play in the narratives with which we construct our professional identity, facilitating professional growth and transformation.Gender, Race and Culture, Age, and Socioeconomic Status were described in 18, 5, 2 and 1 study respectively in relation to professional identity. Self in relation to others was identified as a category within this theme in five studies with narratives of oneself being described as always being in relation to, and constituted by, \u2018other\u2019\u2014supervisors, colleagues, students and family. Relation to others was also described in conceptualisations of professional identity related to the caring aspects of nursing/nursing education interactions\u2014including representing, advocating for and providing for others.Self & Fit was described in a total of 54 or 34% of studies as being important in professional identity. For example, Self & Fit was described as impacting professional identity in relation to fit, or not, between self and work, role or practice expectations, as related to fit with members of the professional group as well as fit with the profession.Tensions exist between the self and developing professional identity and professional identity construction is partially triggered by work-identity integrity violations. acquiring knowledge and skills was discussed in 39 or 24% of studies. Further learning and qualifications was described as important in the differentiation of self from others within the profession with lack of further training and learning opportunities described as hampering professional identity development. Qualifications or credentialing as enhancing professional capital or improving the status of the health professional was discussed in 16 or 10% of papers. Qualifications or credentialling as shaping or controlling the profession were discussed as an influence on professional identity in 10 or 6% or studies.Learning through the This scoping review sought to explore and interrogate the literature on professional identity for practising health professionals in order\u00a0to understand on what disciplines and career stage the evidence is focussed, why the research was undertaken, which theory or framework was used to guide the research and what constructs are used to discuss professional identity. The findings provide insight into professional identity across 17 health professions of 32 investigated. Overall, the majority of studies were in nursing and medicine early in careers with the allied health professions poorly represented. Novel to this review, we identified\u00a0the role of learning and qualifications as contributing to professional identity through increased knowledge and skills and social capital of the profession. Despite the number of studies and the demonstration of commonalities across the professions, this review demonstrates gaps in the research, both in the number of health professions that are represented in the literature as well as issues with theoretical perspectives and critical aspects of the research. Highlighted as well is the imperative for researcher reflexivity including an interrogation of how the agenda for the research into professional identity is set. Future research must further refine theoretical frameworks to develop questions and guide data collection and its analysis or an Identity Approach (role).This scoping review makes an important contribution to the literature by comprehensively examining the rationale and theoretical underpinnings of professional identity research across the health professions as well as exploring the multi-faceted and nuanced nature of professional identity. 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This sentence previously stated:zhangychmd@126.csomzhangychmd@126.comThe corrected sentence appears below: The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Fragaria vesca, commonly known as wild or woodland strawberry, is the most widely distributed diploid Fragaria species and is native to Europe and Asia. Because of its small plant size, low heterozygosity, and relative ease of genetic transformation, F. vesca has been a model plant for fruit research since the publication of its Illumina-based genome in 2011. However, its genomic contribution to octoploid cultivated strawberry remains a long-standing question. Here, we de novo assembled and annotated a telomere-to-telomere, gap-free genome of F. vesca \u2018Hawaii\u00a04\u2019, with all seven chromosomes assembled into single contigs, providing the highest completeness and assembly quality to date. The gap-free genome is 220\u2009785\u2009082\u00a0bp in length and encodes 36\u2009173 protein-coding gene models, including 1153 newly annotated genes. All 14 telomeres and seven centromeres were annotated within the seven chromosomes. Among the three previously recognized wild diploid strawberry ancestors, F. vesca, F. iinumae, and F. viridis, phylogenomic analysis showed that F. vesca and F. viridis are the ancestors of the cultivated octoploid strawberry F. \u00d7 ananassa, and F. vesca is its closest relative. Three subgenomes of F. \u00d7 ananassa belong to the F. vesca group, and one is sister to F. viridis. We anticipate that this high-quality, telomere-to-telomere, gap-free F. vesca genome, combined with our phylogenomic inference of the origin of cultivated strawberry, will provide insight into the genomic evolution of Fragaria and facilitate strawberry genetics and molecular breeding. Arabidopsis thaliana) , and the matter appeared to be settled was used to predict gene models using the transcriptome datasets. Maker (version 2.31.10) [Protein-coding gene structures in the v6.0 genome were predicted using ion 3.3) and Glimion 3.3) , BUSCO (ion 3.3) was used2.31.10) was usedProtein-coding genes were predicted using three methods. KEGG (Kyoto Encyclopedia of Genes and Genomes) annotations were obthttps://orthovenn2.bioinfotoolkits.net/) was used to generate a Venn diagram between v6.0 and v4.0 using an e-value of 1e\u221210. To annotate genes that were newly identified in v6.0, we performed GO analysis with InterProScan 5 (v5.47) to characterize gene functions according to biological process, cellular component, and molecular function terms (http://geneontology.org). We used the R package clusterProfiler to perform and visualize the GO enrichment analysis. We used jcvi [https://github.com/steuernb/NLR-Annotator) to find out the NLR loci. To identify NLR genes in v6.0, we searched the predicted proteome of v6.0 using hmmsearch in HMMER based on the seed NLR (PF00319) from the Pfam database.The complete v6.0 genome assembly was aligned pair-wise to the v4 genome using SyRI (version 1.63) to identify syntenic regions and structural variations . Orthovenn2 ( python) to find F. iinumae genome v1.0, F. viridis YNU genome v1.0, F. nipponica genome v1.0, and F. \u00d7 ananassa FL15.89\u201325 genome v1.0 were obtained from the Genome Database for Rosaceae , and that for R. rugosa was obtained from our established database, http://eplantftp.njau.edu.cn/ [R. rugosa. Finally, according to the four subgenomes of F. \u00d7 ananassa, we used the -a and -at parameters (https://wgdi.readthedocs.io/en/latest/index.html), and we used ASTRAL (v5.7.1) [Protein sets for the .edu.cn/ . We cons.edu.cn/ and then(v5.7.1) to constFragaria species and R. rugosa. The alignment was used as input to IQ-TREE (v1.6.12) [http://timetree.org/).OrthoFinder (v2.4.0) was usedv1.6.12) to generv1.6.12) was usedFei Chen acknowledges funding from the National Natural Science Foundation of China (32172614), a startup fund from Hainan University and a Hainan Province Science and Technology Special Fund (ZDYF2023XDNY050).Z.C. and F.C. designed and led this project. Y.Z., Z.S., Z.X., and M.J. assembled and annotated the genome. Y.Z., C.D., T.G., P.S., S.H., K.W., and J.X. analyzed the data. Y.Z. and F.C. wrote the draft manuscript. Z.C., J.X., and F.C. discussed and revised the draft. All authors have read and agreed to the published version of the manuscript.https://www.ncbi.nlm.nih.gov/) under BioProject accession number PRJNA905123. The genome assembly and annotation data are available at our GDS database: http://eplant.njau.edu.cn/strawberry/.All raw sequencing data generated in this project, including HiFi, Hi-C, Illumina, and ONT data, have been deposited at NCBI (The authors declare that they have no conflicts of interest.Horticulture Research online.Web_Material_uhad027Click here for additional data file."} +{"text": "Spider mites (Acari: Tetranychidae) are dangerous pests of agricultural and ornamental crops, the most economically significant of them belonging to the genera Tetranychus, Eutetranychus, Oligonychus and Panonychus. The expansion of the distribution areas, the increased harmfulness and dangerous status of certain species in the family Tetranychidae and their invasion of new regions pose a serious threat to the phytosanitary status of agro- and biocenoses. Various approaches to acarofauna species diagnosis determine a rather diverse range of currently existing methods generally described in this review. Identification of spider mites by morphological traits, which is currently considered the main method, is complicated due to the complexity of preparing biomaterials for diagnosis and a limited number of diagnostic signs. In this regard, biochemical and molecular genetic methods such as allozyme analysis, DNA barcoding, restriction fragment length polymorphism (PCR-RFLP), selection of species-specific primers and real-time PCR are becoming important. In the review, close attention is paid to the successful use of these methods for species discrimination in the mites of the subfamily Tetranychinae. For some species, e. g., the two-spotted spider mite (Tetranychus urticae), a range of identification methods has been developed \u2013 from allozyme analysis to loop isothermal amplification (LAMP), while for many other species a much smaller variety of approaches is available. The greatest accuracy in the identification of spider mites can be achieved using a combination of several methods, e. g., examination of morphological features and one of the molecular approaches . This review may be useful to specialists who are in search of an effective system for spider mite species identification as well as when developing new test systems relevant to specific plant crops or a specific region Herbivorous mites cause significant damage to agriculturaland ornamental crops. The harmfulness of the mites ismanifested in a decrease in yield and deterioration in thequality of crop production; leads to a decrease in droughtresistance and winter hardiness as well as to the loss ofdecorative properties of cultivated plants . Changes in weather and climateconditions in almost all regions of the world, including theRussian Federation, contribute to a wider spread and massreproduction of pests, transformation of their geographicalhabitats, changes in the population dynamics and trophicrelationships with the host plants , which fully appliesto herbivorous acarofauna , e. g., expansion of habitats, increasedharmfulness, and the emergence of populationsresistant to acaricides have recently been observed in spidermites (Acari: Tetranychidae), one of the main groupsof phytophagous mites . The phytosanitary situation is complicatedby the high risk of introducing quarantine species withthe plant material imported as part of international tradefor the purpose of growing, propagating and selling flowerand other plant products .The Tetranychidae family is subdivided into two subfamilies,Bryobiinae and Tetranychinae, and includes atleast 71 genera and more than 1250 described species,100 of which are dangerous pests .The most common species of the Tetranychidae familybelong to genera Tetranychus, Eutetranychus, Oligonychus,and Panonychus . Amongthem, the two-spotted spider mite (Tetranychus urticaeKoch.) and European red mite (Panonychus ulmi Koch.)are regarded as the most harmful species . T. urticae is ubiquitous and damages a wide rangeof crops as well as ornamental woody and herbaceousplants from various botanical families. The habitats of thetwo-spotted spider mite and other representatives of thisfamily in open-ground agro- and biocenoses have beengradually expanding, covering more and more territoriesof Russia .The harmfulness of the spider mites that damage coniferousplants has been increasing as well. Thus in the southof Western Siberia, the spruce spider mite (Oligonychusununguis Jacobi) damaging the European and Siberianspruces and Siberian fir used for planting greenery in urbanareas has become a threat . The riskof importing quarantine pests with planting material hasalso increased, e. g., the sugi spider mite (Oligonychushondoensis Ehara), invasive for this territory, was found inthe Krasnodar Region .Correct identification of spider mite species is of greatscientific and practical importance for the study of theirpopulation dynamics and timely control of their numbersin agro- and biocenoses as well as for the elimination ofinternational plant quarantine-based trade barriers . Currently, several methods are in use to diagnosethe members of the Tetranychidae family, including identificationby the morphological characteristics of adult aswell as biochemical (protein-based) and molecular (DNAbased)methods. The objective of this review is to considerthe modern methods and approaches used to identify themost common species of spider mites (Tetranychidae:Tetranychinae).At present, the identification of herbivorous mites is carriedout mainly by the traditional methods based on visualexamination of morphological features. The foundationsof the morphological method in determining spider mitewere laid in the former USSR by prominent scientistsV.I. Mitrofanov, I.Z. Livshits and Z.I. Strunkova whohugely contributed to the establishment of a whole area ofscientific research devoted to species Tetranychidae familydiagnosis . The approach wasfurther developed in the research and applied works byS.Ya. Popov et al. , A.K. Akhatov (2016) etal., many of which still remain relevantDetermination of the mite\u2019s genus and species is usuallybased on the shape and size of male genitalia . However, their microscopicsize, slight differences in diagnostic features in the speciesbelonging to the same genus, and the laboriousness of preparingthe biomaterial for analysis significantly complicatetheir morphological identification .Another drawback of this approach is the impossibilityof determining the species based on other stages of theirdevelopment , since diagnostic differencesexist only in adults. Moreover, for some closelyrelated species, morphological identification is almost impossible, e. g., genus Amphitetranychus includes threespecies and only one of them, A. viennensis, can be recognizedby the shape of the aedeagus, while A. quercivorusand A. savenkoae are difficult to separate based on this trait.The slides are prepared using modified Faure\u2013Berlesemedia, of which Hoyer\u2019s medium isthe most common for fixing herbivorous mites and consistsof 50 ml of distilled water, 30 ml of gum arabic, 200 mlof chloral hydrate, 20 ml of glycerin. Mites are placed ina drop of medium on a glass slide and covered with a coverslip.The slide is heated at temperatures of 40\u201360 \u00b0\u0421 withexposure time varying from 24 hours to 5\u201310 days, or3 hours at 70\u201385 \u00b0\u0421 , which contributes tothe clarification and straightening of the mite, so its properdiagnosis can be performed. If slides are to be stored fora long time, one is recommended to dry them additionallyin a thermostat at a temperature of 40\u201345 \u00b0\u0421 for 5\u20137 days.After drying, the edges of the coverslips are filled withvarnish, so the slides can be stored indefinitely. Mite speciesare diagnosed in transmitted light using a phase-contrastmicroscope at a 10 to 1000-time magnification.In general, the morphological method requires considerabletime and is very demanding in terms of qualificationand experience of those who apply it. In some cases, morphologicalidentification is supplemented by ecological andbehavioral responses of the species, as well as by informationon the host plant on which the species has been found,which can facilitate species identification .Some features of the life cycle, such as the diapausingphase, wintering sites, diapause exit time, concentrationon certain organs of host plants, and the specificity ofdamage symptoms, can also play an important role in thespecies diagnosisGenetic incompatibility when crossing closely related speciesof tetranychid mites is considered one of the best criteriafor their discrimination. The reproductive barriers can becaused either by the morphological features orby the death of zygotes, which affects the viability of eggsor manifests itself in a different sex ratio in the offspring.For instance, the experiments of Russian researchers oncrossing between species Tetranychus atlanticus, T. urticae,and T. sawzdargi showed their complete genetic isolation. The reproductive isolation of twomorphologically related species of Amphitetranychus spp.,manifesting itself in the absence of female offspring, wasconfirmed in the reciprocal crossing of A. savenkoae andA. quercivorus .According to a number of scientists , a combination of the morphologicalmethod with the crossing results for closely related ordistant species is a reliable criterion for spider mite speciesdiagnosis. Unfortunately, this method is only applicablefor scientific purposes, and cannot be used for practicalapplications.One of the biochemical methods for identifying speciesof spider mites is allozyme analysis that is protein electrophoresisenabling for efficient detection of enzymepolymorphisms . To perform theanalysis, a single individual is homogenized, its proteinextract is isolated and subjected to electrophoresis. In theelectric field, proteins are separated according to theirsize and net electrical charge. After electrophoresis, thegel is histochemically stained to detect specific enzymes.Based on the number and arrangement of the stained fractions,one can make judgments about the alleles encodinga given enzyme in each individual . For correct identification, it is important to choosethe enzyme system in which there will be no variability instripe patterns within a species andcommon stripes across species .The analysis has been widely used to identify insects and ixodid ticks .It has also been applied for spider mite identification, usingsuch enzymes as esterase, phosphoglucosemerase, andmalate dehydrogenase . Such spider mite species as Panonychus citri andP. mori were first identified using allozyme analysis of esterases. Later it was shown that the samemethod could be used to identify three more species of thePanonychus mites endemic for Japan (seethe Table). Using esterase zymograms, Gotoh et al. (2007)were able to distinguish females of four Tetranychusspecies,and based on the analysis of phosphoglucomutaseisoenzymes \u2013 all 13 Japanese species of genus Tetranychus(see the Table). The allozyme analysis of esterases was alsoused for species diagnosis of the representatives of genusAmphitetranychus . The obtainedzymograms were species-specific and made it possible toconfidentially distinguish all three species (see the Table).Thus, allozyme analysis is an effective tool for identifyingspider mite species and has a much higher resolutionthan the morphological method. However, it does notevaluate all possible allele variants present in populations.Another biochemical method proposed for the identificationof spider mites is matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) that has beena well-established method for identifying microbial species. In recent years, this methodhas also been used to investigate plant pests and insects,such as nematodes, Drosophila fruit flies, mosquitoes, etc..In this method, species identification is achieved viacomparingthe spectra of the studied samples with thesamples from the spectral database of previously identifiedorganisms. The databases provided by instrumentmanufacturers currently do not contain reference spectrafor plant pests and parasites, but the instrument softwareusually provides an option to integrate your own referencespectra into existing databases and subsequently performautomated comparisons .To create the reference spectra, it is necessary to use thesamples whose species have been identified by, e. g., morphologicalmethodsOne of the method\u2019s important advantages if comparedto other identification techniques is the fast sample preparationand short testing time .For diagnosis, it is sufficient having just one individual,whose protein extract must first be isolated using 70 %formic acid and acetonitrile, or the mite can be directlylocated on the metal target of the device, where formic acidand acetonitrile are added, followed by a matrix solution. The method\u2019s main disadvantageis the high cost of the device, but the price of one analysisis very low and includes just the cost of the matrix solutionand the calibration standard (provided that there is areusable steel plate for samples).Kajiwara et al. (2016) showed that closely related speciesof Tetranychus spider mites (see the Table) had differentmass spectra allowing for their identification. Theidentification was performed by comparing the three mainspectral peaks within a m/z range from 2000 to 10 000 correspondingto ribosomal proteins. In adults of both sexes,all three peaks were differentiated, which made it possibleto attribute them to the same species. In the case of nymphs,only two of the three main peaks could be identified. Minorpeaks were either sex- or developmental stage-specific andwere not used for identification .In general, MALDI-TOF MS is a promising method forthe identification of spider mites, but its application is stilllimited and requires further research. In particular, theremay be spectral differences between geographically differentpopulations, which has been shown for some insects,and it is also assumed that the spectra of one speciescan be influenced by its host plant .For the purposes of mite species diagnosis, the molecularmethods based on DNA sequencing are used along withbiochemical ones. In these methods, the DNA fragmentsamplified by PCR serve as biological barcodes to identifythe species a sample belongs to .Both nuclear and mitochondrial genome sequences canbe used as such barcodes. Since more and less conservedregions alternate within a ribosomal DNA cluster , respectively), it becomes possible to selectdifferent marker sequences to separate taxa of differentranks. The 18S and 28S rDNA gene sequences can be usedto compare phylogenetically distant taxa , and the ITS regions are effective for distinguishingbetween species and even populations . Among the mitochondrial genes,the cytochrome c oxidase subunit I (COI ) gene sequenceis used to identify species and analyze phylogenetic relationships.In addition to the Folmer fragment (Barcode ofLife (BOLD), Folmer et al., 1994) being the 5\u2032-terminalsequence of the COI gene, other gene sequences are usedfor barcoding spider mites .In , the authors used the ITS2sequence as a barcode to distinguish 16 species of spidermites of the Tetranychidae family endemic for Israel (seethe Table), and the barcode sequence of each type wasuniquely distinguishable from all others. The effectivenessof the DNA barcoding for species identification was alsoconfirmed by COI gene fragment-based identification ofthe spider mite species collected from agricultural fields inVietnam (see the Table).The results also demonstrated the method\u2019s limitations,e. g., some samples could not be classified due to lack ofsequence information in the databases. Other species, suchas T. urticae and T. turkestani, T. neocaledonicus andT. glovery, could not be uniquely identified by their DNAsequences. The impossibility to distinguish between T. urticaeand T. turkestani based on the COI gene sequence wasalso confirmed in the mites collected in different regions ofRussia and Turkey ,which can be overcome by further accumulation of data onthe sequences of different DNA regions from morphologicallyidentified samples. Matsuda et al. (2013) identifiedthe mite species of genus Tetranychus by sequencing theITS and COI genes. The authors concluded that 10 outof 13 species of the Japanese mites of genus Tetranychuscan be identified using the ITS sequence, while the COIgene sequence made it possible to identify all 13 species(see the Table).In contrast to genus Tetranychus, where some speciescannot be distinguished based on DNA sequences, thismethod proved to be effective for genus Oligonychus, so all 17 Japanese species weresuccessfully distinguished based on any of the sequences, including those that were difficultto differentiate by morphological characters, suchas O. castaneae and O. coffeae (see the Table). Molecularanalysis of the COI gene sequence of the mites of genusAmphitetranychus showed that the sequence is effectivefor the identification of all three species (see the Table).Thus, the DNA barcoding is an effective tool for theidentification of individual genera of spider mites (such as Oligonychus and Amphitetranychus). However, someclosely related species maybe indistinguishable from each other by their barcodesequences,as it has been shown for T. kanzawai, T. parakanzawai,and T. ezoensis having similar ITS sequences; and T. urticae and T. turkestanihaving similar COI gene sequences . For these species, other markergenes should be selected.The desire to reduce the time spent for analysis has ledto the development of faster methods for identifying spidermites, one of these being PCR-restriction fragmentlength polymorphism (PCR-RFLP). In this method,fragments of genomic DNA ,amplified by PCR, are subjected to hydrolysis by restrictionendonucleases. The restriction products are subjectedto gel electrophoresis, so a conclusion can be made aboutthe presence or absence of a restriction site in this sampleand, as a result, a species can be identified.PCR-RFLP is widely used for species identificationof various organisms . In spider mites, the method wasfirst applied to distinguish between three species of genusPanonychus and T. urticae (seethe Table). Later, Gotoh et al. (1998) were able to differentiateT. urticae and T. pueraricola by applying PCR-RFLPto the ITS2 region. In , the authorsapplied the method to the ITS fragment to identify five species of spider mites that inhabitedSpanish citrus orchards (see the Table). The most harmfulwas the common spider mite (T. urticae) that made it necessaryto quickly distinguish it among the others, which wasachieved through the RsaI enzyme patterning the restrictionfragments, while hydrolysis with two other enzymes madeit possible to identify the other four species . The PCR-RFLP applied to ITS regions is usedin the Japanese Imported Plant Quarantine Department and enables one todetect all 14 spider mite species found in Japan, includingfive exotic ones (see the Table). Meanwhile, the PCR-RFLP appliedto the COI region was successfully used to identifyfour spider mite species thriving on cassava in Colombia (see the Table).PCR-RFLP is a relatively inexpensive and effectivemethod for spider mite identification, used in many countriesaround the world . However, it can only beapplied to those species it has been developed for, e. g., toidentify mites in an area whose species composition is wellestablished. When new species are added to the system,their RFLP pattern should be analyzed and, if the patternmatches the existing ones, the system should be modifiedby selecting other diagnostic restrictases. The RFLP patterncan also vary in different populations of the same speciesdue to nucleotide substitutions at the restriction site .Another approach for rapid mite identification has beenselection of species-specific primers. The DNA regionswhere such primers are defined should be common for thespecies being determined, but the sequences themselvesshould differ between species of the same genus . In this case, both whole pairs of species-specificprimers can be used, as well as a combination of oneuniversal primer and the second primer being unique fora particular species. Such primers increase the accuracyand speed of PCR-based identification of spider mite species,but their development is not a trivial task. Khaing etal. (2014) succeeded in selecting pairs of species-specificprimers for the ITS2 region for four species of spider mitesbelonging to genus Panonychus (see the Table). Later, species-specific primers were developed for the spider mitesof genus Tetranychus (see the Table) common in Korea andvery similar morphologically .Combining several species-specific primers in a singletube allows applying the multiplex approach to identifyseveral species at once. In this case, the melting temperatureof the primers should be high, and the resulting amplicons \u2013short, but different in length. Additionally, multiplex PCRrequires selecting amplification conditions, such as the ratioof primer pairs and the elongation time .Z\u00e9l\u00e9 et al. (2018) designed and successfully multiplexedprimers complementary to the ribosomal locus in a singlereaction to identify the most common spider mites foundin southwestern Europe (see the Table). Multiplex PCRhas also been used to discriminate between the two mainspider mite species, T. urticae and T. turkestani found inIranian greenhouses .Using real-time PCR for species identification significantlyreduces the time for analysis because this methoddoes not require gel electrophoresis since the accumulationof the PCR product is monitored directly during the reactionusing optical sensors built into the cycler. Two typesof labels are used to detect a PCR product: intercalatingagents or modified oligonucleotidescontaining fluorophores (DNA probes) . In addition, real-time PCR analysis combines primerannealing and elongation steps, resulting in a shorter reactiontime than conventional PCR .Li et al. (2015) developed the TaqMan PCR detectionsystem to distinguish T. urticae among other closely relatedspecies that has proved to be highly specific and reliable.TaqMan is one of hybridization DNA probes \u2013 an oligonucleotidecomplementary to the amplified internal regionof the DNA fragment, labeled at the ends with fluorophores\u2013 being a reporter and a quencher, respectively.When they are on the same probe, the quencher absorbsthe signal from the reporter. During amplification, the polymerasemoving along the DNA destroys the probe, so thereporter and quencher move away from each other, and the reporter\u2019s fluorescence becomes noticeable . The species-specific primers and probe weredesigned for T. urticae\u2019s ITS1 sequence, since it containedmore intraspecific polymorphisms than the ITS2 sequencewidely used for Tetranychus species phylogeny and identification.Another team developed TaqManspecies-specific probes for the identification of spider mitesthriving in the cotton fields of Australia (see the Table),and selected the conditions for their use in one test tube(multiplex approach). An important feature of this approachwas the possibility of extending it to other types of spidermites with minor modification. Since it used a pair ofprimers universal for spider mites for amplification, it wasnecessary, when adding another species to the test system,to develop and add a species-specific probe for it and selectreaction conditions . The authors usedDNA probes for three species of mites in one reaction andconsidered it was possible to increase their number to five(add or replace with DNA probes for the required species)to diagnose up to five different mite species with one PCR.Another method that can be used for species identificationpurposes is loop mediated isothermal amplification(LAMP) . Unlike the classical PCR,LAMP uses a different thermostable polymerase with highdisplacement capacity that can itself displace the secondstrand without thermal denaturation. That is why LAMPreaction takes place at the same temperature (60\u201365 \u00b0C)and does not require an DNA amplifier. Another featureof LAMP is that not two, but four or six primers are usedduring the reaction, which determines its high specificity. On the other hand, selecting suchprimers for LAMP is a rather laborious task. The reaction\u2019sproduct can be detected in several ways, includingthe naked eye after adding a fluorescent dye to confirm thereaction has taken place . Thus, thismethod not only does not require special equipment orspecially trained specialists, but is also suitable for largescalefield studies .As a well-established technique, LAMP has been usedin a wide range of applications, including the identificationof plant pathogens and insect species . For the identification of thecommon spider mite, a highly sensitive method combiningPCR and LAMP (PCR-LAMP) has been developed . It includes the standard PCR performed priorto isothermal amplification to reduce the false negatives andincrease the sensitivity of the LAMP assay. The authorshave shown that PCR-LAMP is a fast and reliable methodfor T. urticae biomaterial detectionOur review of currently available methods for diagnosingthe most significant species of herbivorous mites (Tetranychidae:Tetranychinae) has demonstrated that a widevariety of approaches have been accumulated that can beused by choice, depending on the goals of species identification.The morphological methods, despite the complexityof required preliminary operations to prepare mitesfor analysis, still remain the main ones in determiningthis group of phytophages. However, the new approachesdeveloped in recent decades and based on biochemicaland molecular markers open up even greater opportunitiesfor faster and more accurate identification of species. Forinstance, some species of spider mites such as T. urticaecan be properly diagnosed using one of the molecularapproaches . At the same time, some other species have not yetbeen diagnosed based on their DNA sequences. In suchcases, the use of several identification methods at onceis justified. Such an integrated approach was applied tothe diagnosis of the species of genus Amphitetranychus whose morphological characteristicswere supplemented by biochemical, and molecular onesand verified in crossing experiments. It is important tonote that several approaches can be implemented on thesame individual, provided that DNA extraction methods areused without destroying the sample or a whole mite is used as a PCR matrix(direct PCR) , and for subsequentmorphological characterization. It has been shown that,after such manipulations, specimens retain their morphologicalfeatures intact, including dorsal setae and aedeagus.The authors declare no conflict of interest.Ahmad F., Babalola O.O., Tak H.I. Potential of MALDI-TOF massspectrometry as a rapid detection technique in plant pathology: identificationof plant-associated microorganisms. Anal. Bioanal. Chem.2012;40(4):1247-1255. 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Exp. Appl. Acarol.2007;42(4):239-262. DOI 10.1007/s10493-007-9092-z.Sakamoto H., Gotoh T. Non-destructive direct polymerase chain reaction(direct PCR) greatly facilitates molecular identification ofspider mites (Acari: Tetranychidae). Appl. Entomol. Zool. 2017;52:661-665. DOI 10.1007/s13355-017-0512-1.Shim J.-K., Khaing T.M., Seo H.-E., Ahn J.-Y., Jung D.-O., Lee J.-H.,Lee K.-Y. Development of species-specific primers for rapid diagnosisof Tetranychus urticae, T. kanzawai, T. phaselus and T. truncatus(Acari: Tetranychidae). Entomol. Res. 2016;46(2):162-169. DOI10.1111/1748-5967.12154.Sinaie S., Sadeghi Namaghi H., Fekrat L. A multiplex PCR assay forsimultaneous discrimination of two predominant spider mites of thegenus Tetranychus (Acari: Tetranychidae) in greenhouses of Iran.J. Agr. Sci. Tech. 2018;20(4):733-744.Sinaie S., Sadeghi-Namaghi H., Fekrat L. Loop-mediated isothermalamplification combined with PCR for specific identification of injuriousmite, Tetranychus urticae (Trombidiformes: Tetranychidae).Biologia. 2019;74(5):477-485. DOI 10.2478/s11756-018-00187-7.Singhal N., Kumar M., Kanaujia P.K., Virdi J.S. MALDI-TOF massspectrometry: an emerging technology for microbial identificationand diagnosis. Front. Microbiol. 2015;6:791. DOI 10.3389/fmicb.2015.00791.Tomita N., Mori Y., Kanda H., Notomi T. Loop-mediated isothermalamplification (LAMP) of gene sequences and simple visual detectionof products. Nat. Protoc. 2008;3(5):877-882. DOI 10.1038/nprot.2008.57.Turak E., Hales D.F. An allozyme method for identifying individualaphids of morphologically similar taxa (Hemiptera: Aphididae).J. Aust. Ent. Soc. 1994;33(1):57-59. DOI 10.1111/j.1440-6055.1994.tb00920.x.Ulyanova E., Andreeva I., Shatalova E. The species composition ofherbivorous acarofauna in the south of Western Siberia. Persian J.Acarol. 2022;11(2):365-370. DOI 10.22073/pja.v11i2.72456.V\u00e1squez C., Colmen\u00e1rez Y. Invasive mite species in the Americas:bioecology and impact. In: Haouas D., Hufnagel L. (Eds.) PestsControl and Acarology. London: IntechOpen, 2020. DOI 10.5772/intechopen.86127.Volkova M.V., Matveikina E.A. Structural changes in the phytophagousmite complex in the commercial vineyards of the Crimea. Plodovodstvoi Vinogradarstvo Yuga Rossii = Fruit Growing and Viticultureof South Russia. 2016;38(2):130-139. (in Russian)Walter D.E., Krantz G.W. Collecting, rearing and preparing specimens.In: Krantz G.W., Walter D.E. (Eds.) A Manual of Acarology. TexasTech Univ. Press, 2009;91-92Zeynalov A.S. Ecological and phytosanitary consequences of climatechange in the plantings of fruit cultures. Uspekhi SovremennoyNauki= Modern Science Success. 2017;2(9):94-100. (in Russian)Zeynalov A.S., Orel D.S. Change in species composition, bioecologyand harmfulness of main applian phytophages in the Central Regionof the Non-Black Earth Zone of Russia under the influence of climatefactors. Vestnik Kazanskogo GAU = Vestnik of the Kazan StateAgrarian University. 2021;16(1):15-21. DOI 10.12737/2073-0462-2021-15-21. (in Russian)Z\u00e9l\u00e9 F., Weill M., Magalh\u00e3es S. Identification of spider-mite speciesand their endosymbionts using multiplex PCR. Exp. Appl. Acarol.2018;74(2):123-138. DOI 10.1007/s10493-018-0224-4."} +{"text": "In the published article, the reference for Pollard and Verstraete (2008) was incorrectly written as:Vet Surg. (2008) 37:294\u20139. doi: 10.1111/j.1532-950X.2008.00380.x\u201d\u201cPollard RE, Verstraete FJM. The diagnostic yield of conventional radiographs and computed tomography in dogs and cats with maxillofacial trauma. It should be:Vet Surg. (2008) 37:294\u20139. doi: 10.1111/j.1532-950X.2008.00380.x\u201d\u201cBar-am Y, Pollard RE, Verstraete FJM. The diagnostic yield of conventional radiographs and computed tomography in dogs and cats with maxillofacial trauma. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "This is the authors\u2019 response to peer-review reports for \u201cThe Exchange of Informational Support in Online Health Communities at the Onset of the COVID-19 Pandemic: Content Analysis\u201d.M. Addressed .Q. Addressed.U. Addressed.1. Addressed.2. Addressed.3. Addressed.4. Addressed.5. Addressed. What we were trying to convey is that people who offered information were more likely to post more than once judging by their action of responding to others\u2019 information requests.6. Emotional support is an interesting topic, but it is out of the scope of this study.7. We are unable to address this comment at this moment, as studies on other public health emergencies with comparable findings are limited.8. Addressed.9. Addressed.10. Addressed.11. Addressed.12. Addressed.1. Addressed.2. We are unable to address this comment at this moment.Methodology section, where previous studies on which our coding ontology is based are cited.3. Please refer to the"} +{"text": "Furthermore, we document the presence of three native species that, despite being repeatedly observed in Sicily and reported in the literature, are inexplicably omitted by the most recent authoritative checklists regarding the flora of Italy. Finally, fifteen alien species new to Sicily are reported and seven poorly documented allochthonous taxa are confirmed for the island, and for two of them, a status change is proposed. These new or confirmed records allow us to better define the European and national distribution of the targeted taxa and offer new insights on the native and alien flora of Sicily.In this paper, based on fieldwork and herbaria surveys, new data concerning the presence of 32 native and alien vascular species for Sicily are provided. Among the native species, the occurrence of the following Moreover, the examination of environments that are still less investigated, such as the numerous artificial basins and tanks found in Sicily, can lead to the discovery of new, mostly alien taxa. A systematic exploration of these environments was recently carried out through the MedIsWet project [During floristic and vegetational research carried out by the authors throughout the whole territory of Sicily, some taxa that were previously never reported or whose presence in Sicily was doubtful were recorded. After the latest checklists of the Sicilian ,2 and It project . At the project ,63,64. Itaxa are recorded for the first time in Sicily, while 13 other species, whose status was doubtful at the regional level, are here confirmed.The aim of this paper is to inform the scientific community about several unpublished new records, partly retrieved from social networks and validated by experts, related both to the native and alien flora of Sicily. In particular, 17 Nerio-Tamaricetea africanae, Phragmito-Magnocaricetea, Potametea pectinati, Saginetea maritimae, Isoeto-Nanojuncetea and Salici-Populetea nigrae.The results bring to light new floristic data concerning 32 taxa for Sicily , of whicAira multiculmis Dumort.Poaceae\u2014T (scap)\u2014Subtrop.\u2014Native.Confirmation for SicilyExsiccatum. Bosco di Santo Pietro , contrada Ogliastro, sandy soils, 200\u2013250 m a.s.l., 18.04.2022, leg. and det. D. Azzaro, s.n. (CAT!).Aira caryophyllea L., which, in Italy, is known for its presence in Tuscany, Campania, Calabria and Sardinia [Helianthemetea guttate Rivas Goday & Rivas-Mart. 1963. In the same area, there are two other species of Aira, from which A. multiculmis is distinguished by certain morphological characteristics. In particular, A. caryophyllea L. is characterized by spikelets, generally > 2.6 mm, and by the inferior glume diverging from the peduncle by less than 80\u00b0 and by a smaller number of culms. A. cupaniana Guss. differs instead with its decidedly rough sheaths, smaller spikelets, sharply enlarged peduncles at the apex and its 2\u20132.5 mm glumes [This is a species related to Sardinia . Its occSardinia , while mSardinia or consiSardinia . The spem glumes . The popAlbuca canadensis (L.) F.M. Leight (. Leight GAsparagaceae\u2014G (rhiz)\u2014S-Afric.\u2014Alien.Confirmation for Sicily and ItalyExsiccatum. Tangenziale di Catania, vicino all\u2019uscita per Misterbianco, roadsides, 100 m a.s.l., 12.04.2022, leg. and det. S. Cambria, s.n. (CAT!).Albuca altissima Dryand.), who reported its naturalization from a ruderal stand inside Catania. This author claims that the species was introduced from the local botanical garden and from there it spread to other areas of the city. Afterwards, the species was no longer recollected and was reported as dubious for Sicily and Italy by various authors [A. canadensis growing on the roadside of the Catania ring road, consisting of almost 100 individuals. It is often found in dry grasslands with Hyparrhenia hirta (L.) Stapf., Isatis tinctoria L., Ferula communis L. and other typical species of the Lygeo sparti-Stipetea tenacissimae Rivas-Mart\u00ednez 1978 class. Here, the presence of this taxon is confirmed for Italy and Sicily. We can state that the species does not represent a threat to the natural habitat 6220* \u201cPseudo-steppe with grasses and annuals of the Thero-Brachypodietea\u201d. The population is circumscribed and does not show an increasing trend to expand into natural environments.This South African species was recorded for the first time in Italy by Nicolosi-Roncati \u2014Asia\u2014Alien.New casual alien species for SicilyObservatum. Roadsides, Augusta (Syracuse), 10 m a.s.l., 09.10.2020, obs. R. Romano, det. F. Luchino.A small population of this species was found in the suburb pavements of Augusta (SE Sicily), probably having escaped from nearby gardens. This species was already known in several regions in Northern and Central Italy .Ambrosia artemisifolia L.Asteraceae\u2014T (scap)\u2014N. Amer.\u2014Alien.New alien species for SicilyObservatum. Castelluzzo, San Vito Lo Capo (Trapani), 150 m a.s.l., 15.07.2020, obs. S. Montoleone, det. R. Guarino.This North American species was observed in very anthropized environments near San Vito Lo Capo (western Sicily). Although it is still very rare in Sicily, its potential for further spread should be monitored, as it also represents one of the main causes of seasonal respiratory allergy in many European countries and in some areas of northern Italy . In ItalAmorpha fruticosa L.Fabaceae\u2014P (caesp)\u2014N. Amer.\u2014Alien.New alien species for SicilyObservatum. Valle del Timeto, San Piero Patti-Librizzi, 450 m a.s.l., 23.05.2013, obs. and det. G. Torre.Salici purpureae-Populetea nigrae Rivas-Mart\u00ednez & Cant\u00f3 ex Rivas-Mart\u00ednez, B\u00e1scones, T.E. D\u00edaz, Fern\u00e1ndez-Gonz\u00e1lez & Loidi 2001. The plant community in which A. fruticosa grows is referable to habitat 92A0 \u201cSalix alba and Populus alba galleries\u201d.This species was already known in all Italian regions as invasive or naturalized, except for Sicily . Our finArum maculatum L. (latum L. AAraceae\u2014G (rhiz)\u2014Europ.\u2014Native.New record for SicilyExsiccatum. Piano Caterineci , orophilous vegetation with Juniperus communis subsp. hemisphaerica, 1590 m a.s.l., 31.05.2016, leg. V. Ilardi and S. Cambria, det. S. Brullo, s.n. (CAT!).Observatum. Bosco della Tassita , Mesophilous woods, 1600 m a.s.l., 23.05.2013, obs. and det. A. La Rosa.Arum maculatum occurs in almost all Italian regions, while it is absent in Sicily and doubtful for Sardinia. Giardina et al. [Arum cylindraceum Gasparr., occurring in nearby localities. However, the two species are distinguished quite easily by the morphology of the underground organs, as A. maculatum has an ovoid tuberous rhizome, longer than broad and horizontally developing, while A. cylindraceum is characterized by a circular \u201cbulb\u201d, from the center of which the scape develops [A. maculatum for Sicily, named nigro-maculatum Fiori and indicated it for Caltanissetta. However, according to Sortino [Arum italicum. Even the bioclimatic features of the aforementioned locality seem to be favorable to this arrangement, since A. italicum is widespread in Sicily at low elevations, while A. maculatum was observed by us only within the supra-Mediterranean bioclimatic belt of the Madonie and Nebrodi mountains in the mesophilous beech forests belonging to Querco roboris-Fagetea sylvaticae Br.-Bl. & Vlieger in Vlieger 1937 or orophilous shrublands dominated by Juniperus communis L. subsp. hemisphaerica (J. Presl & C. Presl) Nyman (Pino sylvestris-Juniperetea sabinae Rivas-Mart\u00ednez 1965 class). The two populations fall within protected areas, such as the Madonie regional park and the Nebrodi regional park, as well as in the SAC Pizzo Fau, Monte Pomiere, Pizzo Bidi and Serra della Testa (ITA030014) and Parco delle Madonie (ITA020050).According to Bartolucci et al. , Arum maa et al. report tdevelops . Pignattdevelops and Pigndevelops ,72,73,74 Sortino , it fallBergenia crassifolia (L.) Fritsch. (Fritsch. FSaxifragaceae\u2014G (rhiz)\u2014Asia\u2014Alien.New alien species for SicilyObservatum. Monacella di Santa Venerina (Catania), 450 m a.s.l., 01.02.2022, obs. M. Pappalardo, det. O. Caldarella.A few individuals of this ornamental species, quite frequent in the gardens of Sicily, were found as casual aliens near the small village of Monacella (Catania), on the eastern flank of Mt. Etna. Previously in Italy, it was reported only in some northern regions .Carex flacca Schreb. subsp. flacca (. flacca ECyperaceae\u2014G (rhiz)\u2014Europ.\u2014Native.New record for SicilyExsiccatum. Serra della Testa, hygrophilous vegetation with Thelypteris palustris, 1050 m a.s.l., 17.06.2021, leg. and det. S. Sciandrello, P. Minissale, D. Azzaro, S. Cambria, s.n. (CAT!).Carex flacca subsp. erythrostachys (Hoppe) Holub is a common species in Sicily; however, as regards the subsp. flacca, there are only a few doubtful records mentioned by Lojacono Pojero [Thelypteris palustris Schott. , recently surveyed by Sciandrello et al. [o Pojero for vario Pojero for Piano Pojero and abseo Pojero . Our fieo et al. .Cornus mas L.Cornaceae\u2014P (caesp/scap)\u2014Eurimedit.\u2014Native.Confirmation for SicilyExsiccatum. Valley below Monte Canalotto, Piazza Armerina, riparian woods, 750 m a.s.l., 22.10.2021, leg. D. Azzaro, S. Cambria and det. S. Cambria, G. Tavilla, s.n. (CAT!).Cornus mas in Sicily had already been reported by Giardina et al. [Cornus sanguinea L., though much less frequently. From a phytosociological point of view, it grows in the riparian forest of Salici purpureae-Populetea nigrae Rivas-Mart\u00ednez & Cant\u00f3 ex Rivas-Mart\u00ednez, B\u00e1scones, T.E. D\u00edaz, Fern\u00e1ndez-Gonz\u00e1lez & Loidi 2001. The surveyed population falls within the SAC \u201cVallone Rossomanno\u201d (ITA060010) and in the regional Nature Reserve \u201cRiserva Rossomanno-Grottascura-Bellia\u201d.The presence of a et al. in certaa et al. ,72,73,74Cydonia oblonga Mill.Rosaceae\u2014P (scap)\u2014W Asia\u2014Alien.Confirmation for Sicily as a casual alienExsiccatum. Valley below Monte Canalotto, Piazza Armerina, riparian woods, 750 m a.s.l., 22.10.2021, leg. D. Azzaro, S. Cambria and det. S. Cambria, G. Tavilla, s.n. (CAT!).Salici purpureae-Populetea nigrae class , protected in the regional Nature Reserve \u201cRiserva Rossomanno-Grottascura-Bellia\u201d and in the SAC \u201cVallone Rossomanno\u201d (ITA060010). However, the few C. oblonga individuals do not currently represent a real threat to this habitat.The naturalization of this species in Sicily had already been reported by Terp\u00f2 , GiardinFagopyrum esculentum MoenchPolygonaceae\u2014T (scap)\u2014Central Asia\u2014Alien.Confirmation for SicilyObservatum. Augusta, ex Saline Regina (Siracusa), Roadsides, 10 m a.s.l., 15.10.2021, obs. and det. R. Romano, A. La Rosa.Fagopyrum esculentum is not reported for Sicily in any recent work concerning the vascular flora of Sicily [f Sicily ,72,73,74f Sicily , withoutGrevillea robusta A. Cunn. ex R. Br.Proteaceae\u2014P (scap)\u2014Australia\u2014Alien.New casual alien species for SicilyObservatum. Catania, 10 m a.s.l., 24.10.2020, obs. and det. F. Gambilonghi.This Australian species, commonly used for road tree planting over the last three decades, was found on the sidewalks and retaining walls of Catania. In Italy, it was already recorded as a casual alien in Lazio and Campania .Honorius nutans (L.) Gray (L.) Gray CAsparagaceae\u2014G (bulb)\u2014W Asia\u2014Alien.Confirmation for SicilyObservatum. C.da Serra Pantano, Caltanissetta, olive groves, 470 m a.s.l., 02.04.2018, obs. and det. A. Cristaudo.The naturalization of this taxon in Sicily was observed only once by Lojacono Pojero near EnnHylotelephium spectabile (Boreau) H. OhbaCrassulaceae\u2014H (scap)\u2014Eurosiber.\u2014Alien.New casual alien species for SicilyObservatum. Oak wood near San Basilio, Novara di Sicilia (Messina) 670 m a.s.l., 08.04.2018, obs. A. Ferrara Curr\u00f2, det. O. Caldarella.Querco-Fagetea class) in the territory of Novara di Sicilia (NW Sicily). In Italy it was already observed as a casual alien in Lombardy, Marche and Umbria [This species, commonly cultivated as an ornamental plant, was found in a deciduous oak wood \u2014Asia\u2014Alien.New record for SicilyObservatum. C.da Campolato, Augusta (Syracuse), dry grasslands, 10 m a.s.l., 02.10.2018, obs. C. Arcidiacono, det. O. Caldarella.Hyparrhenia hirta (L.) Stapf (Lygeo-Stipetea class) on calcarenitic substrates near Augusta (SE Sicily). It was reported as a casual alien by Galasso et al. [This species, often cultivated in gardens as a summer annual, was observed in a coastal grassland dominated by o et al. for mostJuncus foliosus Desf.Juncaceae\u2014T (scap)\u2014Stenomedit.\u2014Native.Confirmation for SicilyExsiccatum. Oxena river, near Militello Val di Catania (eastern Sicily), annual hygrophilous vegetation, 310 m a.s.l., 04.07.2021, leg. and det. D. Azzaro, s.n. (CAT!).Iso\u00ebto-Nanojuncetea Br.-Bl. & T\u00fcxen ex Westhoff, Dijk & Passchier 1946 and Saginetea maritimae Westhoff, Leeuwen & Adriani 1962.Bartolucci et al. and GiarKalanchoe laxiflora BakerCrassulaceae\u2014T (scap)\u2014S.-Afric., Madagascar\u2014Alien.Confirmation as casual alien for SicilyObservatum. Via Fortino, Torre Faro, Messina, 10 m a.s.l., 23.10.2022, obs. and det. V.L.A. Laface.K. laxiflora doubtfully for Toscana and Sicily. Our findings confirm the presence of the species in this region, where it is occasionally cultivated. In fact, the observed population, consisting of a few individuals that probably escaped from nearby gardens, colonize wall cracks near the road, within the SPA \u201cMonti Peloritani, Dorsale Curcuraci, Antennamare e area marina dello Stretto di Messina\u201d (ITA030042).The occurrence of this species as a casual neophyte in Europe and Italy has recently been confirmed by Stinca et al. and SpamLimonium avei (De Not.) Brullo & Erben ( & Erben CPlumbaginaceae\u2014T (scap)\u2014W-Medit.\u2014Native.Confirmation for SicilyExsiccatum. Saline di Nubia presso Paceco (Trapani), 10 m a.s.l., 30.04.2022, leg. and det. M. Aleo (CAT!).Observatum. Isola Grande dello Stagnone , wet clay soils, 5 m a.s.l., 02.03.2022, obs. and det. S. Cambria and G. Tavilla.Limonion avei alliance (Saginetea maritimae).The presence of this species has not been recorded in Sicily by Bartolucci et al. , despiteMentha longifolia (L.) L. ( (L.) L. ALamiaceae\u2014H (scap)\u2014Paleotemp.\u2014Native.New record for SicilyExsiccatum. Serra della Testa (Nebrodi), hygrophilous vegetation, 1000 m a.s.l., 17.06.2021, leg. and det. S. Sciandrello, P. Minissale, D. Azzaro, S. Cambria, s.n. (CAT!).M. spicata L., from which it is mainly distinguished by the presence of only simple straight hairs and lanceolate leaves, with maximum width towards the median part [Phragmito australis-Magnocaricetea elatae Klika in Klika & Nov\u00e1k 1941 communities and the surveyed population falls within the Nebrodi Regional Park.The species is not mentioned by Giardina et al. , while iian part ,72,73,74Morus alba L.Moraceae\u2014P (scap)\u2014E Asia\u2014Alien.New record for Sicily as casual alienExsiccatum. Valley below Monte Canalotto, Piazza Armerina, riparian woods, 750 m a.s.l., 22.10.2021, leg. D. Azzaro, S. Cambria and det. S. Cambria, G. Tavilla, s.n. (CAT!).Populus nigra and P. alba colonizing a narrow valley in central Sicily, we report for the first time Morus alba as a casual alien for the Sicilian flora. This location is protected in the regional Nature Reserve \u201cRiserva Rossomanno-Grottascura-Bellia\u201d and in the SAC \u201cVallone Rossomanno\u201d (ITA060010).Despite being commonly cultivated, this species has never been ascribed to the allochthonous flora of Sicily. Based on the observation of some young individuals in the riparian vegetation dominated by Najas minor All. (nor All. BHydrocharitaceae\u2014I (rad)\u2014Paleotemp.\u2014Native.New record for SicilyExsiccatum. Artificial basin of Cozzo Ogliastri, 381 m a.s.l., 30.07.2021, leg. and det. L. Tosetto, F. Luchino, S. Cambria, s.n. (CAT!).Observatum. Artificial basin near Roccamena, 470 m a.s.l., 02.04.2018, obs. and det. S. Costa, O. Caldarella and A. La Rosa.Najas minor partly retain their vitality after digestion and can germinate in polluted waters. In Italy, Najas minor is recorded only in northern and central regions, as well as in Sardinia [Conspicuous populations of this species were found in two artificial ponds near Roccamena and in a small water reservoir near Melilli (Syracuse). It constitutes a dense, monophytic aquatic vegetation with a summer optimum. Considering that the species has never been reported for Sicily and its presence seems so far restricted to man-made habitats, it is possible to hypothesize its relatively recent arrival on the island. According to Volk , the sprSardinia .Nymphaea x marliacea Lat.-Marl. (t.-Marl. DNymphaeaceae\u2014I (rad)\u2014horticultural origin\u2014Alien.New record for Sicily as casual alienExsiccatum. Artificial pond in Contrada Cella di Fico near Isnello , 742 m a.s.l., 14.08.2019, leg. and det. S. Cambria, s.n. (CAT!).Potamogeton pusillus, Scirpoides holoschoenus, Juncus inflexus, Juncus effusus and Epilobium hirsutum, characterizing an aquatic community of Potametea pectinati Klika in the Klika & Nov\u00e1k 1941 class. The origin of this Nymphaea population is somewhat uncertain, since the site has been abandoned for many years and the distance from the inhabited centers and gardens is quite significant. In any case, the taxon at issue belongs to a complex of horticultural hybrids, whose putative parental species are N. alba L., N. mexicana Zucc. and N. odorata Aiton [N. x marliacea has been so far reported as a casual alien only in northern regions, such as Lombardia and Trentino-Alto Adige [This horticultural hybrid was observed in an artificial pond, built as a water reservoir for the irrigation of nearby agricultural lands in the 1970s and today is in disuse, located within private property occupied by a livestock farm. Over the years, the basin became naturalized and has been colonized by various aquatic and hygrophilous species, such as ta Aiton . Based oto Adige ,93. It mOenothera lindheimeri (Engelm. & A. Gray) W.L. Wagner & Hoch \u2014N. Amer.\u2014Alien.Change of status from casual alien to naturalizedObservatum. Lido Fiori beach near Menfi (Agrigento), 10.08.2022, obs. and det. O. Caldarella.Oenothera lindheimeri was reported for the first time in Sicily as a casual species by Galasso et al. [Euphorbio paraliae-Ammophiletea australis G\u00e9hu & Rivas-Mart\u00ednez in Rivas-Mart\u00ednez, Asensi, D\u00edaz-Garretas, Molero, Valle, Cano, Costa & D\u00edaz 2011 \u201d).o et al. . FollowiOxybasis chenopodioides (L.) S. Fuentes, Uotila & Borsch.Chenopodiaceae\u2013 T (scap)\u2014Subcosmop.\u2014Native.Confirmation for Sicily.Exsiccatum. Biviere di Gela (southern Sicily), lakeshores, 10 m a.s.l., 07.08.2002, leg. and det. S. Sciandrello and S. Brullo, s.n. (CAT!).Chenopodium botryoides Sm.) by Brullo and Sciandrello [Oxybasis chenopodioides but hypothesized its regional extinction due to the age of the collected specimen and the current dense urbanization of this locality. Therefore, based on our data, it is possible to confirm the current presence of this species in Sicily, where the species is linked to thero-hygrophilous vegetation with the summer\u2013autumn development of Nanocyperetalia flavescentis Klika 1935.This species was reported for the first time in Sicily \u2014S. Amer.\u2013 Alien.New naturalized alien species for SicilyExsiccatum. Milazzo, presso l\u2019Istituto Professionale Agrario (IPSAA), 10 m a.s.l., 03.07.2010, leg. and det. A. Cristaudo, s.n. (CAT!).Observatum. Piana di Milazzo, nelle vicinanze dei Vivai Torre, 40 m a.s.l., 22.06.2022, obs. and det. G. Torre.This species, native to tropical America, is cultivated in gardens for its ornamental qualities. Its ability to disseminate itself is well known among gardening enthusiasts and, in fact, the presence of the species as a casual alien has been already reported in Sardinia by Galasso et al. . AccordiPhacelia tanacetifolia Benth.Hydrophyllaceae\u2014T (scap)\u2014N. Amer.\u2013 Alien.New casual alien species for SicilyObservatum. Marina di Modica (Ragusa), 5 m a.s.l., 16.04.2020, obs. C. Spadaro, det. R. Guarino.This North American species, adventitious in almost all regions of central-northern Italy, including Sardinia , is somePontederia crassipes Mart. (es Mart. BPontederiaceae\u2014I (rad)\u2014S. Amer.\u2014Alien.Change of status from casual alien to invasiveExsiccatum. Canalizzazioni del Fiume Ciane (Siracusa), 5 m a.s.l., 21.09.2006, leg. and det. R. Guarino, s.n. (PAL!).P. crassipes has been repeatedly reported as a casual alien in Sicily [Ranunculion fluitantis and Callitricho-Batrachion vegetation\u201d.This species was recorded for the first time in Sicily by Bartolo et al. , who obsn Sicily ,72,73,74Pyrus betulifolia Bunge (ia Bunge FRosaceae\u2014P (caesp/scap)\u2014E Asia\u2014Alien.New record for Sicily and Europe as a casual alienExsiccatum. Patern\u00f2 (Catania), near Pietralunga bridge, scrublands, 89 m a.s.l., 15.10.2019, leg. and det. A. Cristaudo, F. Carruggio, s.n. (CAT!).Pyrus betulifolia is a wild pear native to eastern Asia and, in particular, to north-central and south-east China, Laos, Manchuria and Tibet [P. betulifolia is listed in the Invasive Plant Atlas of the US, but it does not appear to be a species with significant invasive potential [P. betulifolia occurs within very scattered thermo-hygrophilous vegetation with Tamarix africana Poir. and T. gallica L. \u201d), which occurs also in the nearby areas next to the Simeto river. The origin of this population can almost certainly be related to the use of this species as rootstock for \u2018Coscia\u2019 pear (Pyrus communis), as reported by Stern et al. [nd Tibet . Accordind Tibet . Moreoveotential . Accordiotential , seeds cn et al. for IsraSecale cereale L. subsp. cerealePoaceae\u2014H bienn\u2014Asiat.\u2014Alien.New record for Sicily as a casual alienObservatum. Loc. Contrada San Leo, Belpasso, 1000 m a.s.l.; loc. Caldera, Contrada Simita e Tarderia, Pedara, 830\u2013870 m a.s.l.; Contrada Mompilieri, Nicolosi, 640 m a.s.l. (Catania), 27.07.2021, obs. F. Mascia and N. Serafica, det. F. Mascia.Secale cereale has been reported since the end of the XVIII century [Irmana, had a substantial increase during the Second World War and was later almost completely abandoned [Lupinus albus L. and Vicia faba L. fields.In Sicily, the traditional cultivation of century , mainly bandoned and was bandoned . In the bandoned . In Italbandoned ,106. In Solidago gigantea AitonAsteraceae\u2014H (scap)\u2014N. Amer.\u2014Alien.New record for Sicily as a casual alienObservatum. Pace del Mela (Messina), 100 m a.s.l., 2.10.2022, obs. and det. F. Berenato.Scrophulario-Helichrysetea italici Brullo, Scelsi & Spampinato 1998 near Pace del Mela (Messina), colonizing the edges of ditches and canals. This species was observed within the habitat 3250 \u201cConstantly flowing Mediterranean rivers with Glaucium flavum\u201d.This North American species is reported as casual or naturalized in the regions of central-northern Italy, Abruzzo and Calabria . In SiciSymphyotrichum x salignum (Willd.) G.L. NesomAsteraceae\u2014NP\u2014N. Amer.\u2014Alien.New record for Sicily as a casual alienObservatum. Pace del Mela (Messina), 100 m a.s.l., 2.10.2022, obs. and det. F. Berenato.Symphyotrichum x salignum, probably a natural hybrid between S. novi-belgii and S. lanceolatum, was surveyed in disturbed aspects of Scrophulario-Helichrysetea vegetation (habitat 3250 \u201cConstantly flowing Mediterranean rivers with Glaucium flavum\u201d) near Pace del Mela (Messina). In Italy, it was reported in most of the northern and central regions and Sardinia [Xiphion junceum (Poir.) Parl. (.) Parl. EIridaceae\u2014G (bulb)\u2014W-Stenomedit.\u2014Native.Confirmation for SicilyObservatum. Olive Groves, Spadafora (Messina), 200 m a.s.l., 14.04.2015, obs. A. Scoglio, det. A. La Rosa.This species, native to Iberian Peninsula, Northern Africa and Sicily , was recWith a surface of 25.711 km\u00b2, Sicily represents the largest island in the Mediterranean Sea, located immediately south of the Italian Peninsula . Sicily\u2019According to the phytogeographic classification proposed by Brullo et al. and subshttp://dryades.units.it/floritaly/index.php, accessed on 27 August 2022) and \u201cActa Plantarum\u201d . Syntaxonomic classification follows Mucina et al. [The floristic data are based on field investigations carried out from 2015 to 2022, herbaria surveys and bibliographic analysis. The collected or examined plant materials are preserved mainly in CAT herbarium or private herbaria. Nomenclatures, taxonomic concepts and notes on the regional distribution are based mainly on the checklists published by Giardina et al. and Galaa et al. .taxa are arranged in alphabetical order. For each taxon, according to Pignatti et al. [Specimens were identified according to Pignatti et al. ,72,73,74i et al. ,72,73,74i et al. . DetailsAira multiculmis, Arum maculatum and Najas minor are recorded for the first time in the native flora of Sicily, while Carex flacca subsp. flacca, Cornus mas, Juncus foliosus, Limonium avei, Mentha longifolia, Oxyasis chenopodioides and Xiphion junceum are confirmed for the island, since their presence on the island, as indicated by some authors, was considered doubtful in the recent literature, mainly due to very old or vague reports. In regard to non-native species, the occurrence of Albuca canadensis, Honorius nutans, Fagopyrum esculentum, Kalanchoe laxiflora and Cydonia oblonga are confirmed after some decades. Finally, Pontederia crassipes is recorded as invasive and Morus alba, Nymphaea x merlata, Allium tuberosum, Grevillea robusta, Ambrosia artemisifolia, Impatiens balsamina, Hylotelephium spectabile, Bergenia crassifolia, Secale cereale, Symphyotrichum x salignum, Solidago gigantea, Phacelia tanacetifolia, Passiflora morifolia, Pyrus betulifolia and Amorpha fruticosa are recorded as casual aliens for the first time in the region. The new findings for the native flora confirm the remarkable floristic richness of the island, which, in spite of what can be hypothesized on the basis of the numerous floristic studies recently published on the Sicilian territory, is still worthy of further study. Furthermore, the results obtained in this research confirm the rapid increase in exotic species even in natural environments; thus, in some cases, the careful monitoring of species with greater invasive potential is advised. Particular attention must be paid to protected areas, such as the sites of the Natura 2000 network, mentioned several times here in the new records, where alien species can cause damage or alteration to the habitats of conservation importance [This paper presents new data concerning 32 taxa of native and non-native vascular species for Sicily . In partportance .Thus, having a continuous account of new records allows the planning of early preventive actions for their further diffusion, saving on future high management costs . In conc"} +{"text": "J Am Heart Assoc. 2023;12:e028424. DOI: 10.1161/JAHA.122.028424) and was included in the April 4, 2023 issue of the journal, a correction was needed.In the article by Camilla H. B. Jespersen et al, \u201cUse of Nonrecommended Drugs in Patients With Brugada Syndrome: A Danish Nationwide Cohort Study,\u201d which published online March 21, 2023 (The name of the 16th author, Jacob Tfelt\u2010Hansen, was incorrectly written in the published article as Jacob Tfelt Hansen. This error has now been corrected.The authors regret the error.https://www.ahajournals.org/doi/10.1161/JAHA.122.028424.The online version of the article has been updated and is available here:"} +{"text": "Scientific Reports 10.1038/s41598-021-03392-8, published online 15 December 2021Retraction of: The Editors have retracted this Article.3. The Editors therefore consider this article to be redundant.After publication concerns were raised about the originality of the work presented. Investigation has shown significant overlap with other sources, notablyWasim Jamshed and Kottakkaran Sooppy Nisar disagree with the retraction. S. Suriya Uma Devi, Rabha W. Ibrahim, Faisal Shahzad, Mohamed R. Eid, Abdel-Haleem Abdel-Aty, M. Motawi Khashan, and I. S. Yahia did not reply to the correspondence about the retraction. The Editors were not able to obtain a current email address for M. Prakash."} +{"text": "Siphlonurusdongxi Li & Tong, sp. nov. from Shangri-La City, Yunnan Province, China, is described based on egg, nymph, and winged stages. The new species is closely related to S.davidi , and can be distinguished by the colour of the imago, the forking point of MP, the penis, posterolateral spines of tergum IX of imagoes, and first abdominal terga nymph, as well as the structure of the egg. The new species and S.davidi have the same morphological and structural characteristics, such as the long cubital area with many intercalaries, cross veins between C, Sc, RA, and RSa1 surrounded with distinct pigments, the strong curvature of vein CuP in the forewing, the broad expansion of the hindwing, the membranous penis lobes fused without teeth, supporting the proposition of a new species complex, the Siphlonurusdavidi group. The structures of the penis and the egg of the new species could help understand the origin and evolution of the genus Siphlonurus. Siphlonurus Eaton, 1868 is characterized by many plesiomorphies is distributed in China. It was initially described from a single male subimago , eggs were dried, coated with gold, and observed with a VEGA3 SBU SEM . Measurements were taken using ImageJ image processing software. The final plates were prepared with Adobe Photoshop CC 2018.MBDU).All examined materials were deposited at the Museum of Biology, Institute of Eastern-Himalaya Biodiversity Research, Dali University, Dali, Yunnan, China , China, Yunnan Province, Shangri-La City, Jiantang Town, Dugang river, 27\u00b047\u203250.4\u2033N, 99\u00b048\u203243.3\u2033E, 3361 m a.s.l., 12.VI.2022, coll. Xian-Fu Li. Paratypes: 13 nymphs, 30 imagoes and 8 subimagoes reared from nymphs with same data as holotype. 5 nymphs from same location as holotype, but 1.VI.2021, coll. Yi-Hao Fang.S.davidi. It can be distinguished from S.davidi by the colour of the imago, the morphological structure of egg, the forking point of MP, the transversal sclerite of the penis with two dorsal elongations, the dorsal elongation of the penis basally expanded, the elongations of the ventral sclerite, the posterolateral spines of tergum IX of imagoes and the first abdominal terga of the nymph, as well as the structure of the egg.The new species is similar to Male imago (in ethanol). Body length 18.4\u201320.5 mm (excluding cerci), head width 3.3\u20133.5 mm, forewing length 17.3\u201318.6 mm, hindwing length 7.8\u20138.1 mm, antennae 1.4\u20131.6 mm. Ratio of hindwing: forewing length about 0.43.Head: compound eyes contiguous Fig. similar ol) Fig. ; forewinol) Fig. and hindol) Fig. subhyalileg Fig. = 1.4:1.leg Fig. = 1.5: 1leg Fig. = 1.5: 1leg Fig. . The sclleg Fig. . Styligeleg Fig. . Forewinleg Fig. .Female imago (in ethanol). Colour pattern similar to male; body length 19.6\u201322.2 mm, head width 3.1\u20133.4 mm, caudal filaments 20.7\u201324.4 mm, forewing 18.5\u201321.3 mm, hindwing 9.0\u20139.4 mm . Similar to male subimago except the tarsal segments of foreleg with more spines and usual sexual differences are shown in Fig. Winged stages of Eggs. Oval with irregular flat areas light yellow with red and dark markings Fig. , body lelar Fig. , surfacelar Fig. . Abdomenlar Fig. , posterolar Fig. . Abdominlar Fig. light yelar Fig. ; posterilar Fig. . Middle lar Fig. . Caudal lar Fig. . Gills dlar Fig. trianglelar Fig. leaf-shalar Fig. and II . We hope that the Institute of Eastern-Himalaya Biodiversity Research can become an important platform for biodiversity research in the world. At the same time, we hope to cooperate with scientists from all countries through the International Centre of Biodiversity and Primate Conservation (http://www.icbpc.org/index.html).The specific epithet China (Yunnan).Nymphs of this new species prefer to live in pools or slow current areas with aquatic plants close to the bank in clear, high-altitude, wide streams Fig. . The lasSiphlonurus species, S.binotatus Eaton, 1892 : fig. 3 Siphlonurusdongxi Li & Tong, sp. nov. is closely related to S.davidi, whose adults share the markings of the wings, the strong curvature of vein CuP, the broad expansion of the hind wing, the longer cubital area in the forewing, and the membranous penis lobes fused without teeth. Siphlonurusdongxi Li & Tong, sp. nov. and S.davidi differ from all other described Siphlonurus species in these characters (Siphlonurusdavidi group, should be distinguished.aracters , which oSiphlonurusdavidi group, such as the following characters:There are significant differences within the S.davidi are reddish brown, whileS.dongxi Li & Tong, sp. nov. are light yellow and dark brown.Imagoes ofS.davidi is subequal to the fusion point of MA and RS, then MP2 bends backwards strongly near to CuA. This condition is common in Ephemeridae and Potamanthidae, and is similar toSiphlonuruschinensis (Ulmer, 1920; S.dongxi Li & Tong, sp. nov..Forking point of MP in forewing ofS.davidi has only membranous lobe, but the penis lobe ofS.dongxi Li & Tong, sp. nov. has long elongations of ventral sclerite.Penis ofS.dongxi Li & Tong, sp. nov. imagoes are well developed. While, the ones ofS.davidi are poorly developed.Posterolateral spines of tergum IX ofS.davidi nymph have distinct posterolateral spines, while the spines ofS.dongxi Li & Tong, sp. nov. are only on segments 2\u20139.All abdominal terga ofS.dongxi Li & Tong, sp. nov. has micropyle, but inS.davidi the egg exochorionic surface is without micropyle (The egg exochorionic surface oficropyle : fig. 7.S.dongxi Li & Tong, sp. nov. and S.davidi suggest that the existence of a species bridging the gap between them is possible.These numerous and significant differences between S.davidi and other ones. The discovery of this new species bridges the gap between S.davidi and other Siphlonurus species, and could help reveal the origin and evolution of the genus Siphlonurus.Obviously, the new species shows characteristics that fall somewhere between"} +{"text": "Communications Biology 10.1038/s42003-022-04157-3, published online 17 November 2022.Correction to: In the Acknowledgements section, the National Institutes of Health grant to authors D.A.C. and T.J.B. should have read \u201cR01GM138411\u201d. The original article has been corrected."} +{"text": "Prognostic impact of physical activity patterns after percutaneous coronary intervention. Protocol for a prospective longitudinal cohort. The PIPAP study By Gonzalez-Jaramillo N, Eser P, Casanova F, Bano A, Franco OH, Windecker S, R\u00e4ber L and Wilhelm M. (2022) Front. Cardiovasc. Med. 9:976539. doi: 10.3389/fcvm.2022.976539An Erratum on An omission to the funding section of the original article was made in error. The following sentence has been added: \u201cOpen access funding was provided by the University Of Bern\u201d.The original version of this article has been updated."} +{"text": "Dear Editor,Marburgvirus. It is closely related to the Ebola virus. Marburg marburgvirus, only species causing a zoonotic disease called Marburg virus disease (MVD) in humans, manifests as skin rash, nausea, vomiting, malaise, hemorrhage, and feverRousettus aegyptiacus. Since African fruit bats reside in caves and are extensively distributed across Africa; these might have infected humans, although the exact mechanism of transmission from fruit bats to humans is still unknownMarburg virus (MARV) is a rare yet deadly pathogen, an RNA virus belonging to the order: Mononegavirales, family: Filoviridae, genus: MVD is a fatal infection with a significant potential to become an epidemicDue to ongoing COVID-19 pandemic and overlapping features between COVID-19 and MVD, it becomes difficult for a physician to accurately differentiate COVID-19 and MVD. Table No antiviral has been accepted as the appropriate treatment for MVD, neither is any approved vaccine for itWorld is already afflicted with multiple outbreaksNot commissioned, externally peer reviewed.Not applicable.None.Conceptualization and editing: A.N. Writing: A.N., S.T., S.M.H.Z., Q.M., F.N., S.G., A.A.W. Review with critical comments: A.N. and S.T.The authors declare that they have no financial conflict of interest with regard to the content of this report.Not applicable.All authors."} +{"text": "Nature Communications; 10.1038/s41467-022-35060-4;published online 26 November 2022Correction to: The original version of this Article omitted from the author list the author Manisha Jalan, who is from the Department of Biochemistry, University of Oxford. Consequently, the following was added to the Author Contributions: A.K., S.T., M.O.N., J.O., and M.J.: conceived and performed experiments. E.B. and C.A. performed experiments; C.A.M. and F.O. provided reagents, expertise, and feedback; M.C.W. conceived experiments, wrote the paper, and secured funding\u2019. This has been corrected in both the PDF and HTML versions of the Article."} +{"text": "The response of 250 common winter wheat breeding lines was investigated for resistance to the causative agent of Puccinia triticina under conditions of an infected field on the territory of Dobrudzha Agricultural Institute \u2013 General Toshevo, Bulgaria, during three successive seasons. Twenty lines with different degrees of resistance under field conditions were selected. Multi-pathotype testing was used to study the response of these lines at seedling stage under greenhouse conditions to individual pathotypes of P. triticina. Based on the response of the lines at seedling and adult stages, we found out that 20 % of them carried race-specific resistance. One of the lines (99/08-52) reacted with full resistance to the pathotypes used under greenhouse conditions. The reaction demonstrated by this line coincided with the response of isogenic lines carrying the genes Lr9, Lr19, Lr22a, Lr22b and Lr25. The other three lines showed a resistant reaction to 6 or 5 of the pathotypes used in the study. Their response partially coincided with the reaction of 5 isogenic lines, and the presence of some of these genes in the above lines is quite possible. Lines carrying this type of resistance are to be subjected to further genetic and breeding investigations to prove the presence of a race-specific gene. Twenty-five percent of the lines combined partial race-specific resistance at seedling stage with the resistance of race non-specific nature at adult stage. Forty percent of all studied lines carried race non-specific resistance, and 15 % of the lines possessed resistance of the \u201cslow rusting\u201d type. As a result of the study we carried out, the lines that demonstrated stable resistance to leaf rust can provide sufficient protection of the host and can be included in the breeding programs for developing varieties resistant to P. triticina. Leaf rust is one of the most widespread diseases on wheatin Bulgaria and one of the most important diseases in thoseparts of the world, where wheat is the main cereal crop. Thedevelopment and growing of resistant cultivars is an important,efficient, environmentally friendly and cost-effective methodfor control of the disease . In order to avoid the danger of epiphytotic occurrence,it is necessary to have at our disposal a large numberof sources \u2013 carriers of different genes or types of resistance,which should be properly alternated in the production fields. According to Van der Plank (1963),the resistance can be categorized into two classes based onthe genetic control and the phenotypic effect \u2013 race specific and race non-specific .The specific resistance is determined by one or several genesacting independently of one another and is efficient to individualraces of the pathogen . Each geneensures resistance to all races that do not have a respectivegene for virulence, but not to races that do not possess sucha gene. When this resistance is realized in a widely distributedcultivar, high selection pressure on the pathogen occurs, leadingto the formation of new races with new genes for virulence,i. e. this type of resistance quickly loses its efficiency, becausethe pathogen population evolves .The non-specific resistance ensures protectionof the plants against all races of the pathogen and the genes,which determine it, have additive effect. The polygenic natureof this type of resistance is the reason for its durability. It is expressedat adult stage and its mechanism consists in reduction in theamount and rate of the disease . The impact of the qualitative resistance of the host onthe evolution of the pathogen populations is less documentedin the literature . It has been shown thatthe fungal pathogens may evolve and adapt to qualitative resistancethrough breeding for higher aggressiveness .Especially interesting is the resistance of a non-specificnature \u2013 the \u201cslow rusting\u201d type, or the retarded developmentof the pathogen. The cultivars possessing this type ofresistance allow the pathogen to sporulate on them, to attackthem to a moderate degree, without forcing the pathogen todevelop new more aggressive races . The genes determining this type ofresistance are related to such factors as pustule size, infectionfrequency, latent period, and are most often defined as \u201cslowrusting genes\u201d . Although the genes determining adult stage resistanceare considered to determine durable resistance, some authorspoint out that the occurrence of new and aggressive races ofthe pathogen may make these genes inefficient . This is the reason why it is necessary to search forand develop new sources of resistance . Hussain et al. (1999) concluded that durable rustresistance mechanism in wheat is achieved through incorporationof partially resistant minor genes, which seems to be moreappropriate for sustainable wheat production.The method based on the \u201cgene for gene\u201d relation is oneof the fundamental concepts of the relationship between theplants and the pathogens . Based on this hypothesis,Person (1959) developed a method for identificationof genes for resistance with the help of testing races of thepathogen, which carry certain virulence. The multipathotypetest used for determining the sources of resistance at seedlingstage by comparing the response of the tested sources to thereaction of the isogenic lines allows investigating a large numberof sources and the obtained information can be used forthe development of resistant cultivars. The gene postulation,determined through the multipathotype test, is the most widelyapplied method worldwide for proving the presence of racespecificity and for identification of certain Lr genes in differentwheat populations . The multipathotype test, however,has certain shortcomings. Kadkhodaei et al. (2012) pointedout that the identification of Lr genes is rather labor and timeconsuming. Furthermore, there may be no available pathotypessuitable for identification of the genes for resistance presentin the genotypes, or the pathotype may not be able to detectthe genes for resistance to rust.Starting from these premises and estimating the difficultiesand disadvantages of the use of the multipathotype test, ourinvestigation, too, could not achieve complete and thoroughidentification of a gene, but only a suggestion; on the basisof the response of these lines at seedling and adult stages,however, the nature of the resistance was determined, whichalso provides valuable data that can aid the breeding andimprovementwork for development of cultivars resistant tothe disease.The aim of this investigation was to study the response ofcommon winter wheat lines both at seeding and adult stagesand to use the obtained data on stable resistance present inthese lines to aid the breeding for development of cultivarsresistant to Puccinia triticinaIn the infection field of Dobrudzha Agricultural Institute \u2013General Toshevo, Bulgaria, the reaction to leaf rust (P. triticina)of 250 lines of common winter wheat involved ina competitive varietal trial was studied. From the investigatedbreeding material, 20 lines were selected, which respondedwith a certain degree of resistance from moderate to high(MR\u2013VR), and which demonstrated resistant reaction to someof the used pathotypes of P. triticina at seedling stage undergreenhouse conditionsSeedling test. The selected 20 lines were tested for resistanceto single pathotypes of P. triticina and their responsewas compared to the reaction of a set of 34 differential lines accordingto the 7 pathotypes used in the study, which possessed differentvirulence . The pathotypes used in the test were identified on thebasis of the reaction of 15 monogenic lines, Lr1, Lr2a, Lr2b,Lr2c, Lr3, Lr9, Lr11, Lr15, Lr17, Lr19, Lr21, Lr23, Lr24, Lr26and Lr28, coded for by the method of Limpert and M\u00fcller(1994). Avirulence/virulence profiles of P. triticina pathotypesare present in Table 1.The inoculated plants were placed in the dark in a moistchamber at temperature 18\u201320 \u00b0\u0421 and 100 % relative airhumidity. After 24 hours at these conditions, they were transferredto a greenhouse for further growing under controlledconditions: 20\u201325 \u00b0C (day) and 15 \u00b0C (night), more than75 % relative air humidity and 30,000 lx light intensity, forelongation of the photo period \u2013 16 h (day) and 8 h (night)In order to improve sporulation, the plants were treatedwith maleic hydrazide 97 % solution (1 g in 3 l water). Onthe 9\u201312th day after inoculation, the type of reaction (R) wasread according to the scale of Stakman et al. (1962).Infection types 0, 0;, 1 and 2 were considered expression ofa resistant type of reaction (R), while infection types 3, 4 and Xwere considered susceptible (S) while estimating the disease.Adult plant test. The investigation was carried out underconditions of a maximum infection created in the field, wherethe full set of pathotypes identified for the respective year weretaken out. The lines were planted manually in 1.5 m widerows with 0.25 m interspacing, in two replications. CultivarMichigan amber was used as a multiplier and distributor ofleaf rust. Spreader rows of M. amber were planted perpendicularand adjacent to the test rows. The artificial inoculationwith the pathogen was done according to the methodology forworking with rusts adopted at the Plant Pathology Laboratoryof Dobrudzha Agricultural Institute . Nine-dayold seedlings from the standard susceptible cultivar M. amberinoculated with different pathotypes of P. triticina were plantedin the rows of the spreader cultivar in March and April till thefinal accumulation of inoculum in June, when the maximumwas reached. The type of infection and the attacking rate wereread according to the scale of Cobb, modified by Peterson at milk maturity stage. The averagecoefficient of infection (ACI), or the so called corrected relativeattack rate (P0), was calculated by introducing a coefficientfor the respective infection types . Depending on the values of ACI,the studied lines were divided into several groups: immune(ACI = 0); very resistant, VR (ACI = 0\u20135.99); resistant, R(ACI = 6\u201325.99); moderately resistant, MR (ACI = 26\u201345.99);moderately susceptible, MS (ACI = 46\u201365.99); susceptible, S(ACI = 66\u2013100). The lines with susceptible reaction were ofno interest to us.The experiment was carried out in three successive vegetativegrowth seasons. Out of the investigated 250 commonwinter wheat lines, 20 lines were selected, which respondedwith high to moderate resistance over the years of study. Thelines responding with MR probably carry slow-rusting genes.According to Morgunov et al. (2010), some genes with slowrustingeffect have a moderately susceptible type of infectionbut their attack rate does not exceed 50 %. The response ofthe lines investigated under field conditions is presented in Table 2, and the reaction of the lines at seedling stage toseven separate P. triticina pathotypes of different virulenceis given in Table 3. The results of the investigation revealedthe following.Line 60/05-49 at seedling stage exhibited a resistant reactionto four phenotypically different pathotypes (see Table 3), andthe field evaluation showed that this line had a resistant to veryresistant reaction (see Table 2). This allows us to commentthat the line is a carrier of partial race-specific resistance incombination with resistance of non-specific nature, but therace-specific resistance has to be checked at a later stage.Line 15/05-82 demonstrated a susceptible reaction to allpathotypes of the pathogen used under greenhouse conditions,and the field evaluation showed that the line responded witha very resistant to resistant reaction. According to this reactionexhibited at seedling and adult stages, the line can be definedas a carrier of adult or field resistanceLine 60/05-68, also at seedling stage, responded witha susceptible reaction to all pathotypes used in the study, andthe field evaluation showed a resistant to moderately resistantreaction. The response of the line allowed referring it to thegroup of the carriers of the slow rusting type of resistanceLine 20/05-120 at seedling stage responded with a susceptiblereaction to all used pathotypes, and in the field itexhibited resistance of the type (VR\u2013R\u2013MR), but judgingby the reaction, this line can be referred to the group of linescarrying resistance of race non-specific nature.Line 98/05-95 at seedling stage demonstrated a resistantreaction to two pathotypes (33762 and 53762), and the fieldevaluation was not constant; in 2014, when the attack oncultivar M. amber was even higher in comparison to the othertwo years, the lines responded as moderately susceptible. In2015 and 2016, the line demonstrated a resistant to moderatelyresistant reaction. This line carried resistance of race nonspecificnatureLine 223/05-2 responded with a resistant reaction to threepathotypes under greenhouse conditions and with completeresistance at adult stage. The line was a carrier of partial racespecificresistance in combination with race non-specific oneLine 13/08-87 at seedling stage responded with a resistantreaction to only one pathotype (53762), and its field resistancewas of the VR\u2013R type. The line was a carrier of resistance ofrace non-specific nature.Line 44/08-66 responded with a resistant reaction at seedlingstage to two pathotypes (43773 and 73763), and duringtwo of the years it demonstrated field resistance of theMR type. Based on the response of the line, it was referredto the group of lines of the slow rusting type.Line 18/08-16 as well as line 19/08-28 responded witha resistant reaction at seedling stage to three of the pathotypesand demonstrated R to VR under field conditions, allowingus to refer them to the group of lines combining partial racespecificresistance with race non-specific one. The combinationof these two types of resistance in a single genotype isa good solution for breeding since the host is protected againstdiseases during the entire vegetative growth season.Line 14/08-57 demonstrated stable field resistance and a resistantreaction to two of the pathotypes under greenhouse conditions.The line was a carrier of race non-specific resistance.Line 46/08-27 reacted with stable resistance in the fieldduring the three years of testing, and at seedling stage, itdemonstrated a resistant reaction to only one pathotype. Theline carries resistance of race non-specific nature.Line 79/08-10 responded at seedling stage with a resistantreaction to two pathotypes (33762 and 53723), and in the fieldit demonstrated a resistant to very resistant reaction. The lineis a carrier of race non-specific resistance.Line 72/08-23 showed a resistant to very resistant reactionin the field, and under greenhouse conditions, a resistant reactionto four pathotypes was registered. The line is a carrierof partial race-specific resistance in combination with racenon-specific one.Line 90/08-22 exhibited a resistant to very resistant reactionin the field, while responding with a resistant reaction toonly one pathotype at seedling stage. This line is probablya carrier of adult race specific resistance or resistance of racenon-specific natureLine 99/08-52 responded with a resistant reaction to all7 pathotypes used in this study, and the field evaluation waswithin the range of R\u2013MR. The presence of full resistance atseedling stage was a proof that the line possessed race-specificresistance. Its reaction coincided entirely with the reactionof the isogenic lines carrying genes Lr9, Lr19, Lr22a, Lr22band Lr25 (Table 4).As a result of this study, we identified the following types ofresistance in the investigated lines:Lines with race-specific resistance, which are to be subjectedto breeding and genetic studies to prove the presenceof the race-specific gene \u2013 four of the lines probably carriedthis type of resistance: 19/06-108, 99/08-52, 82/08-35 and82/08-43. They constituted 20 % of all investigated lines\u2022 Lines combining partial race-specific resistance at seedling stage with resistance of race non-specific nature at adultstage. The combination of race-specific with race nonspecificresistance is a good possibility to protect the hostagainst the disease during the entire vegetative growth.The lines that fall in this group are 60/05-49, 223/05-2,19/08-28, 18/08-16, 72/08-23. They constituted 25 % ofthe investigated lines.\u2022 Lines-carriers of race non-specific resistance. The nonspecificnature of resistance is determined by the fact thatat adult age, the host is resistant to all races and in thiscase the resistance is determined by 4 or 5 small geneswith additive effect. Lines 15/05-82, 98/05-95, 14/08-57,46/08- 27, 79/08-10, 90/08-22, 44/08-88 and 13/08-87fell in this group. They constituted 40 % of all studiedlines.\u2022 Lines-carriers of the slow rusting type of resistance: lines20/05-120, 44/08-66 and 60/05-68 belonged to this groupand they constituted 15 % of the investigated material.The partial resistance is more durable than the resistanceconditioned by single main genes since it is inherited polygenically.The lines studied in this investigation are carriers of certaintypes of resistance. According to Volkova et al. (2020), thecultivars with race-specific resistance are applied as a mosaicof varieties with subsequent alternation over time and space,and the cultivars that carry non-specific resistance can be usedon large areas for a longer period of time in combination withcultivars from different groups, including their own.In this relation, the studied lines carrying race-specific orrace non-specific resistance can be included in the breedingprograms for developing resistant cultivars in order to avoidlarge yield losses caused by the disease.The authors declare no conflict of interest.Bariana H.S. Breeding for disease resistance. In: Thomas B., MurphyD.J., Murray B.G. (Eds.) Encyclopedia of Applied Plant Sciences.Harcourt, Acad. Press, 2003;244-253.Bariana H.S., Brown G.N., Bansal U.K., Miah H., Standen G.E., Lu M.Breeding triple rust resistant wheat cultivars for Australia using conventionaland marker-assisted selection technologies. Aust. J. Agric.Res. 2007;58(6):576-587. 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Agric.2019;18(5):1014-1023. DOI 10.1016/S2095-3119(19)62575-X."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-018-31143-9, published online 24 August 2018Correction to: This Article contains errors in the author list, where Swaranjit Singh Cameotra is inadvertently omitted.As a result, the Author Contributions section should read:P.R. conceived, organized and finalised the study. U.J.K. performed the experiments, collected the data. S.P. and U.J.K. carried out the macrophage intracellular survival assay. U.J.K and S.S.C carried out the FAAS related studies. U.J.K., P.R., S.P. interpreted the data and drafted the manuscript. All authors have critically reviewed and approved the final manuscript.In addition, the Acknowledgements should read:The authors acknowledge the help provided by the Instrumentation laboratory, IMTECH, Chandigarh for carrying out FAAS studies. The authors express their gratitude to Dr. Kanthi Kiran Kondepudi, Scientist-C, National Agri-Food Biotechnology Institute, Mohali, for providing assistance to carry out proteomics related work. The consumables were procured through funds provided by the ICMR project grant [No. 5/3/3/9/2013-ECD-I] provided to Professor Praveen Rishi.The corrected Supplementary Information file is linked to this correction notice.Supplementary Information."} +{"text": "Goniaderini Lacordaire, 1859 and Lupropini Lesne, 1926 within the tenebrionid subfamily Lagriinae Latreille, 1825 have previously been shown to be non-monophyletic by molecular phylogenetic analyses. The tribes and constituent genera are here reviewed and redefined morphologically. As part of tribal redefinitions, we establish PrateiniNew Tribe with type genus Prateus LeConte, 1862. We reestablish the subtribe Phobeliina Ardoin, 1961 Revised Status, which is transferred from Goniaderini and placed as a subtribe of Lagriini Latreille, 1825 where it is comprised of Phobelius Blanchard, 1842, and Rhosaces Champion, 1889 . The fossil tribe Archaeolupropini Nabozhenko, Perkovsky, & Nazarenko, 2023 is transferred from Lagriinae to Tetratomidae: Tetratominae Billberg, 1820. Keys to extant tribes and subtribes of Lagriinae and genera of Goniaderini, Lupropini, and Prateini are provided. Generic and species-level changes from this work are as follows:The tribes Prateini is comprised of the following 15 genera: Antennoluprops Schawaller, 2007, Ardoiniellus Schawaller, 2013, Bolitrium Gebien, 1914, Enicmosoma Gebien, 1922, Indenicmosoma Ardoin, 1964, Iscanus Fauvel, 1904, Kuschelus Kaszab, 1982, Lorelopsis Champion, 1896, Mesotretis Bates, 1872, Microcalcar Pic, 1925, Micropedinus Lewis, 1894, Paratenetus Spinola, 1845, Prateus, Terametus Motschulsky, 1869, and Tithassa Pascoe, 1860. Lorelus Sharp, 1876 is Returned to Synonymy with Prateus, resulting in the following 49 New Combinations: Prateusangulatus , P.angustulus , P.armatus , P.biroi , P.blairi , P.brevicornis , P.breviusculus , P.caledonicus , P.carolinensis , P.chinensis , P.clarkei , P.crassicornis , P.crassepunctatus , P.cribricollis , P.curvipes , P.dybasi , P.fijianus , P.fumatus , P.glabriventris , P.greensladei , P.guadeloupensis , P.hirtus , P.ivoirensis , P.kanak , P.kaszabi , P.laticornis , P.latulus , P.longicornis , P.mareensis , P.marginalis , P.niger , P.norfolkianus , P.obtusus , P.ocularis , P.opacus , P.palauensis , P.politus , P.priscus , P.prosternalis , P.pubescens , P.pubipennis , P.punctatus , P.quadricollis , P.queenslandicus , P.rugifrons , P.solomonis , P.tarsalis , P.unicornis , and P.watti . Microlyprops Kaszab, 1939 is placed as a New Synonym of Micropedinus resulting in the following New Combinations: Micropedinusceylonicus and M.maderi . LorelopsisRevised Status is revalidated as a genus and eight species formerly in Lorelus are transferred to it resulting in the following six New Combinations: Lorelopsisbicolor , L.glabrata , L.exilis , L.foraminosa , L.minutulis , L.trapezidera , and L.wolcotti . Lorelopsispilosa Champion, 1896 becomes a Restored Combination.Goniaderini, Aemymone Bates, 1868 Revised Status and Opatresthes Gebien, 1928 Revised Status, which were recently considered as subgenera of Goniadera Perty, 1832, are restored as valid genera based on new character analysis resulting in the following New Combinations: Aemymonehansfranzi , A.simplex , A.striatipennis and Restored Combinations: Aemymonecariosa , A.crenata Champion, 1893, and A.semirufa Pic, 1917. Gamaxus Bates, 1868 is Returned to Synonymy with Phymatestes Pascoe, 1866, and the type species Gamaxushauxwelli Bates, 1868 is placed as a New Synonym of Phymatestesbrevicornis . The following seven genera are placed as New Synonyms of Anaedus Blanchard, 1842: Microanaedus Pic, 1923, Pengaleganus Pic, 1917, Pseudanaedus Gebien, 1921, Pseudolyprops Fairmaire, 1882, Spinolyprops Pic, 1917, Spinadaenus Pic, 1921, and Sphingocorse Gebien, 1921. Fourteen species described by Pic in Aspisoma Duponchel & Chevrolat, 1841 are returned to Tenebrionidae as valid species of Anaedus. These synonymies necessitate the following 51 New Combinations: Anaedusalbipes , A.amboinensis , A.amplicollis , A.anaedoides , A.angulicollis , A.angustatus , A.australiae , A.bartolozzii , A.beloni Fairmaire, 1888), A.biangulatus , A.borneensis , A.carinicollis , A.conradti , A.cribricollis , A.gabonicus , A.himalayicus , A.inaequalis , A.jacobsoni , A.lateralis , A.latus , A.longeplicatus , A.maculipennis , A.major , A.nepalicus , A.nigrita , A.notatus , A.pakistanicus , A.pinguis , A.punctatus , A.raffrayi , A.rufithorax , A.rufus , A.serrimargo , A.sumatrensis , A.terminatus , A.testaceicornis , A.testaceipes , A.thailandicus , A.trautneri ; and 13 restored combinations: Anaedusboliviensis , A.claveri , A.diversicollis , A.elongatus , A.guyanensis , A.holtzi , A.inangulatus , A.inhumeralis , A.mendesensis , A.minutus , A.rufimembris , A.rufipennis , A.subelongatus . The new synonymies with Anaedus necessitate the following six New Replacement NamesAnaedusmaculipennis , A.grimmi , A.minimus , A.merkli , A.ottomerkli , A.schawalleri .In Capeluprops Schawaller, 2011 is removed from Lupropini and provisionally placed in Laenini Seidlitz, 1895. Plastica Waterhouse, 1903 is transferred from Apocryphini Lacordaire, 1859 to Laenini. Paralorelopsis Marcuzzi, 1994 is removed from Lupropini and provisionally placed in Lagriinae incertae sedis. Pseudesarcus Champion, 1913 is transferred from Lagriinae incertae sedis to Diaperinae incertae sedis. Falsotithassa Pic, 1934 is transferred from Lupropini to Leiochrinini Lewis, 1894 (Diaperinae). Mimocellus Wasmann, 1904 is transferred from Lupropini to Tenebrionidae incertae sedis, and likely belongs in either Diaperinae or Stenochiinae. DedicationDuring the preparation of this publication, one of us, our respected colleague and friend Ott\u00f3 Merkl (1957\u20132021), passed away suddenly on his way to work. In his honor and in recognition of his help with this and other papers, we have named two species ofAnaedusafter him.Tenebrionidae Latreille, 1802 presently contains 2,307 valid genera placed in 12 subfamilies are recovered outside of the clade containing Goniadera Perty, 1832 and related genera. Phobelius was recovered in Lagriini Latreille, 1825, and the remaining genera were recovered in a clade with two genera currently classified in Lupropini . A second clade of Lupropini was also recovered containing Luprops Hope, 1833 and Coxelinus Fairmaire, 1869. Although these issues were evident in the phylogenetic tree, the authors refrained from making taxonomic changes until a more detailed study of morphological characters could be conducted.In the previously described studies, neither ers Fig. . Both arPrateus and Lorelus, by Theodore J. Spilman (1925\u20131996) and John T. Doyen , clearly a problem. The resulting conclusion that Prateus was morphologically mischaracterized in its tribal placement caused a cascade of taxonomic and nomenclatural discoveries and an ever-widening set of issues, eventually with global implications. This fits with the problems of tribal definitions exposed by the molecular work, and this paper and two smaller taxonomic works , United States National Museum of Natural History, Washington D.C., USA (USNM), Natural History Museum, London, UK (NHMUK), Hungarian Natural History Museum, Budapest, Hungary (HNHM), and Montana State University\u2019s Michael A. Ivie collection (MAIC) and the West Indian Beetle Fauna Project, Montana State University (WIBF), as well as personal collections of Rolf Aalbu (RLAC), Kojun Kanda (KKIC), and Andrew Johnston (MAJC). Dissections and study of defensive glands were performed using protocols described by Specimens used in this study are deposited in the Specimens were examined with various stereomicroscopes. Photographs were made by use of the following systems: (1) Macropod Pro (Macroscopic Solutions), with a Canon EOS 5dsr camera body and 65mm lens. Images were stacked using Zerene Stacker v. 1.04. (2) A Nikon D5600 camera body mounted on a Stackshot rail system (Cognisys Inc.) equipped with a Laowa 60 mm or 25 mm macro lens. Images were stacked using Zerene Stacker v. 1.04. (3) A Zeiss Discovery.V20 Stereomicroscope with a Zeiss Axiocam 305 Color camera. Images were stacked using Zerene Stacker v. 1.04.Lagriinae and absence of abdominal defensive glands.Lagriinae, this character combination is only shared with Cossyphini Latreille, 1802. These two tribes can easily be distinguished from each other by the general habitus; all species of Cossyphini have prominent pronotal and elytral flanges, and the pronotal flange covers the head. In Prateini, the pronotum never covers the head. Cossyphini also has medial hinging between abdominal sternites V\u2013VII and intersegmental membranes are not visible, while Prateini has lateral hinging between abdominal sternite V\u2013VII and intersegmental membranes are visible.In Antennoluprops Schawaller, 2007a, Ardoiniellus* Schawaller, 2013, Bolitrium Gebien, 1914, Enicmosoma Gebien, 1922, Indenicmosoma Ardoin, 1964, Iscanus Fauvel, 1904, Kuschelus* Kaszab, 1982a, Lorelopsis Champion, 1896, Mesotretis Bates, 1872, Microcalcar Pic, 1925, Micropedinus Lewis, 1894, Paratenetus Spinola, 1845, Prateus LeConte, 1862, Terametus* Motschulsky, 1869 and Tithassa Pascoe, 1860.Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusLeConte, 1862AFC0D311-07E6-5709-9E13-1251603A6D28PrateusPrateusfusculus Leconte, 1862. LeConte, 1862: 238. Type species: =LorelusLoreluspriscus Sharp, 1876. syn. rest. , comb. nov.Prateusangustulus , comb. nov.Prateusarmatus [Trogosita], comb. nov.Prateusbiroi , comb. nov.Prateusblairi , comb. nov.Prateusbrevicornis , comb. nov.Prateusbreviusculus , comb. nov.Prateuscaledonicus , comb. nov.Prateuscarolinensis , comb. nov.Prateuschinensis , comb. nov.Prateusclarkei , comb. nov.Prateuscrassicornis , comb. nov.Lorelussternalis Broun, 1910. Synonymy by = Prateuscrassepunctatus , comb. nov.Prateuscribricollis , comb. nov.Prateuscurvipes , comb. nov.Prateusdybasi , comb. nov.Prateusfijianus , comb. nov.Prateusfumatus [Mesotretis], comb. nov.Prateusglabriventris , comb. nov.Prateusgreensladei , comb. nov.Prateusguadeloupensis , comb. nov.Prateushirtus , comb. nov.Prateusivoirensis , comb. nov.Prateuskanak , comb. nov.Prateuskaszabi , comb. nov.Prateuslaticornis , comb. nov.Prateuslatulus , comb. nov.Prateuslongicornis , comb. nov.Prateusmareensis , comb. nov.Prateusmarginalis , comb. nov.Prateusniger , comb. nov.Prateusnorfolkianus , comb. nov.Prateusobtusus , comb. nov.Prateusocularis , comb. nov.Prateusopacus , comb. nov.Prateuspalauensis , comb. nov.Prateuspolitus , comb. nov.Prateuspriscus , comb. nov.Prateusprosternalis , comb. nov.Prateuspubescens , comb. nov.Prateuspubipennis [Mesotretis], comb. nov.Prateuspunctatus , comb. nov.Prateusquadricollis , comb. nov.Prateusqueenslandicus , comb. nov.Prateusrugifrons , comb. nov.Prateussolomonis , comb. nov.Prateustarsalis , comb. nov.Lorelusnigrescens Broun, 1910. Synonymy by = Prateusunicornis , comb. nov.Prateuswatti , comb. nov.Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusLewis, 18940392DDF4-A1C6-53B6-8F90-54E38C7341E8MicropedinusMicropedinusalgae Lewis, 1894. Lewis, 1894: 370. Type species: =NotoprataeusNotoprataeuslitoralis Carter, 1924. Synonymy by Carter, 1924:37. Type species: =MicrolypropsMicrolypropsceylonicus Kaszab, 1939. syn. nov. Kaszab, 1939: 108. Type species: Microlyprops was first suggested by Kaszab in his unpublished annotations within his physical copy of Gebien\u2019s Catalog , p. 497\u201d. Moreover, he placed the Microlyprops specimens in the material of Micropedinus in the collection of the Hungarian Natural History Museum, Budapest. One of the co-authors, Otto Merkl, studied this material and confirmed the synonymy, but had not yet taken images before his passing. This synonymy results in the following species-group changes: Micropedinusceylonicus , comb. nov. and Micropedinusmaderi , comb. nov.This genus is known from littoral habitats in the Australasian, Indomalayan, and eastern Palearctic regions. The synonymy of Catalog complemeTaxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusChampion, 1896stat. rev.81801DC3-91BD-5ECB-A88C-AD662C4C7354LorelopsisLorelopsispilosa Champion, 1896. Champion, 1896: 15. Type species: Lorelopsispilosa, from St. Vincent in the Lesser Antilles, comparing it to Lorelus. He mentioned the lobe beneath the fourth tarsomere; pronotum narrower than elytra; erect, fine dorsal pubescence; and closed mesocoxal cavities as distinguishing generic characters. The only other species ever placed in Lorelopsis was when Loreluswolcotti Doyen, 1993 and listed Wolcott\u2019s citation as a synonym but did not mention having actually seen the specimens cited by Wolcott. Lorelopsis is probably not distinct from Lorelus.\u201d Lorelopsis as a valid genus in Prateini based upon several characters mentioned in the key and discussion below. Further, we move several species described in Lorelus by Lorelopsis. The new concept of this genus includes the species given in the checklist below, though a number of undescribed species are also known from the West Indies. Note that us and this was followed by all subsequent workers through We reestablish Lorelopsisbicolor , comb. nov.Lorelopsisglabrata , comb. nov.Lorelopsisexilis , comb. nov.Lorelopsisforaminosa\u2020 , comb. nov.Lorelopsisminutulis\u2020 , comb. nov.Lorelopsispilosa Champion, 1896, comb. rest.Lorelopsistrapezidera , comb. nov.Lorelopsiswolcotti , comb. nov.Prateini, Lorelopsis species are small, elongate, parallel-sided, and covered in fine, silky, erect to suberect setae. The pronotum is slightly to distinctly narrower than the base of the elytra and microspiculate on the lateral margin, each spicule with an associated projecting seta forming a fringing row of projecting setae. A distinct and newly observed character is a long, stout projecting seta on the dorsum of the head close to the hind edge of the eye. This seta is clearly visible in species with relatively sparse and short setae on the head or have patterned elytra.Head: Eyes reniform, anteriorly notched by canthus, rarely completely divided. Antennae moderately long, usually reaching past base of pronotum; antennomeres obconical to filiform.Thorax: Pronotum shape variable, usually cordate, constricted at base, sometimes quadrate to rectangular. Lateral margins complete. Procoxae clearly separated by prosternal process. Mesocoxal cavity laterally closed, at least partially, by mesepimeron. Elytra striate or not. Metathoracic wings well developed . Legs slender, not fossorial, penultimate tarsomeres lobed or cupuliform.Abdomen: Intersegmental membranes visible between sternites V\u2013VII, abdominal hinging tenebrionoid. Defensive glands absent. Ovipositor either stout with four distinct gonocoxites and terminal gonocoxite digitate or greatly reduced with gonocoxites fused see Goniaderini can be distinguished from Lupropini and Prateini by having the mesocoxal cavities laterally open and abdominal defensive glands absent.Lagriinae, this combination of characters is shared with Belopini Reitter, 1917, Chaerodini Doyen, Matthews & Lawrence, 1990, Eschatoporini, and Laenini , and no intersegmental membrane is visible between the sternites; the aedeagus is oriented so the tegmen is ventral, as in the majority of Pimeliinae; penultimate tarsomeres are not lobed or cupuliform. Goniaderini has lateral abdominal hinging between sternites V\u2013VII (tenebrionoid hinging), and the intersegmental membranes between these segments are visible; aedeagus is oriented so the tegmen is dorsal; penultimate tarsomere is either lobed or cupuliform.In Chaerodini contains just two genera found on sandy shores in Australia and New Zealand. They exhibit features typical of psammophiles, including having a globose body, fossorial protibiae, and shortened antennae. Chaerodini also has an antennal club composed of five antennomeres and very reduced ovipositors that lack apical gonostyli. Goniaderini is not globose, at most only the elytra are inflated; protibiae are not fossorial; and antennae extend past the anterior margin of the pronotum and are not clubbed. The ovipositor is shortened and reduced in some groups , but gonostyli are always present.Eschatoporini contains just one genus with two species restricted to Northern California. These species inhabit caves with natural water and are sometimes found at entrances to underground springs. The eyes are completely absent. Goniaderini possesses well-developed reniform eyes. Although Eschatoporini and Goniaderini both lack sternal defensive glands, the former possesses a pair of cuticular sac-like reservoirs between tergites VII and VIII. This character seems to be unique within Tenebrionidae, and their function is unknown , are larger than most Aemymone. Aemymone differs from Anaedus by (1) having clearly defined, punctate elytral striae, (2) lacking posterior pointing denticles on the lateral margin of elytra near the base, and (3) by having a slight metallic sheen in some species.analyses . In factone Fig. is likelGoniadera and Opatresthes, as subgenera in their work, based upon the presence of setae (we find that both genera have setae), color of the integument (we find this character unreliable), and the sides of pronotum . Both Goniadera and Opatresthes, unlike Aemymone, have the basal tarsomere of the hind tarsi equal or subequal to the terminal tarsomere. These two genera can be further separated from each other by (1), the strongly explanate anterior two-thirds of the pronotum in Opatresthes (only at most slightly explanate sides of the pronotum in Goniadera), (2) the lateral aspect of both the pronotum and elytra being strongly dentate/tuberculate in Opatresthes , (3) the metaventrite is equal to or shorter than the first visible abdominal ventrite in Opatresthes , and (4) general shape, Goniadera being narrower and more elongate than Opatresthes.Aemymone and Opatresthes is summarized in the following checklists. Note that many authorship and year attributions of The reinstatement of Taxon classificationAnimaliaColeopteraTenebrionidaeGenusBates, 1868stat. rev.14C9E077-1B5C-5D3C-A6F9-355F7401F975AemymoneGoniaderacariosa Bates, 1868. Bates, 1868: 314. Type species: Aemymonecariosa [Goniadera], comb. rest. Note: Goniaderiacariosa Bates, 1868, for an unavailable Dejean species of the same name, and later in the same paper designated this species as the type species for Aemymone. cariosa\u201d, but the only species with that epithet he included within the genus was one described by Aemymonestriatipennis below.Aemymonecrenata Champion, 1893, comb. rest.Goniaderachampioni Ferrer & Delatour, 2007. Replacement name due to secondary homonym. Note: When Aemymone as a subgenus of Goniadera, this resulted in Goniaderacrenata [Aemymone] becoming a secondary homonym of Goniaderacrenata Perty, 1832. Goniaderachampioni Ferrer & Delatour, 2007 was proposed as a replacement name for G.crenata .= Aemymonehansfranzi [Goniadera], comb. nov.Aemymonesemirufa Pic, 1917a, comb. rest.Aemymonesimplex [Goniadera], comb. nov.Aemymonebordoni Marcuzzi, 1994. Synonymy by = Aemymonestriatipennis [Anaedus], comb. nov. Synonymy with A.cariosa Fairmaire, 1873 by Goniaderacariosa Fairmaire, 1873. Junior primary homonym (in Goniadera) and secondary homonym (in Aemymone) of Goniaderacariosa Bates, 1868.= Aemymonesilvanae Marcuzzi, 1994. Synonymy by = Goniaderacariosa Fairmaire, 1873 is a primary homonym of Goniaderiacariosa Bates, 1868, and now that both species are included in Aemymone, it is also a secondary homonym. Although both species may have been described to accommodate an unavailable Dejean species by the same name , which was synonymized by Aemymonecariosa is considered the valid name. Type specimens of both species must be examined before a decision can be made about whether Fairmaire\u2019s A.cariosa is a subjective synonym of Bates\u2019.As noted above, Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusGebien, 1928stat. rev.6A970DCD-0061-5723-AB58-FDFF92646381OpatresthesOpatresthesbinodosa Gebien, 1928. Gebien, 1928: 192. Type species: Opatresthesbinodosa Gebien, 1928, comb. rest.Opatresthesquadrinodosa Gebien, 1928, comb. rest.Opatresthesmaesi [Goniadera], comb. nov.Opatresthestuberculifera [Goniadera], comb. nov.Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusPascoe, 18668910DDAD-787A-5B9D-A091-95BEE7E48EC5PhymatestesLagriatuberculata Fabricius, 1787. Pascoe, 1866: 142. Type species: =GamaxusGamaxushauxwellii Bates, 1868. syn. rest. and thus G.hauxwelli Bates, 1868 is considered a new synonym of P.brevicornis .During this study, the holotype of 868 Fig. was examTaxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusBlanchard, 18428F8310BC-E759-514A-9D24-80853B48CCC7AnaedusAnaeduspunctatissimus Blanchard, 1842 . Duponchel & Chevrolat, 1841: 240. Type species: =AnaedesAnaeduspunctatissimus Blanchard, 1842. Unjustified emendation, not in prevailing usage eyes reniform, not completely divided; (2) pronotum transverse, always wider than long, never divided by narrow waist; (3) femora lacking teeth and spines; (4) tarsal formula 5-5-4; (5) elytra with basal lateral margin distinctly serrate; (6) elytral striae in most species, at least confused basally, usually confused throughout entire length.Anaedus is most similar to Aemymone, Lyprochelyda, and Ancylopoma. From Aemymone, it can be distinguished by the setae on the lateral margin of the elytra placed on the lateral carina . In most species of Anaedus, elytral punctures are nearly always confused . In Anaedus, the basal lateral margin of the elytron is distinctly serrate and the structure of the prothorax, which is described as transverse, laterally crenulate, regularly arched, with posterior corners prominent , comb. nov. and Anaedusbartolozzii , comb. nov.dus Fig. , known frominent . Both thPengalenganus, known from the Indomalayan region, was also distinguished from Anaedus by the structure of the pronotum, which was described as short, strongly incised anteriorly in the middle, with anterior angles prominent, very constricted posteriorly to the middle, laterally margined and flattened, and laterally posteriorly incised , comb. nov., Anaedusangustatus , comb. nov., and Anaedustestaceicornis , comb. nov. incised . AlthougPseudanaedus , and is not diagnostic. Therefore, Pseudanaedus Gebien, 1921 is placed as a synonym of Anaedus resulting in: Anaedusbiangulatus , comb. nov. and Anaedusconradti , comb. nov.dus Fig. , with twPseudolyprops , comb. nov.Anaedusalbipes , comb. nov.Anaedusamboinensis , comb. nov.Anaedusamplicollis , comb. nov.Anaedusaustraliae , comb. nov.Anaedusbeloni , comb. nov.Anaedusborneensis , comb. nov.Anaeduscarinicollis , comb. nov.Anaedusgabonicus , comb. nov.Anaedusjacobsoni , comb. nov.Anaeduslatus , comb. nov.Anaeduslongeplicatus , comb. nov.Anaedusmajor , comb. nov.Anaedusnigrita , comb. nov.Anaeduspinguis , comb. nov.Anaeduspunctatus , comb. nov.Anaedusraffrayi , comb. nov.Anaedusrufus , comb. nov.Anaedussumatrensis , comb. nov.Anaedusterminatus , comb. nov.Anaedustestaceipes , comb. nov.Spinolyprops , comb. nov.Anaedusmaculipennis nom. nov. for Spinolypropsmaculatus Kulzer, 1954: 21. Distribution: Sri Lanka. Secondary homonym of Anaedusmaculatus Champion, 1886: 25. Distribution: Nicaragua and Panama.Anaeduscribricollis , comb. nov.Anaedushimalayicus , comb. nov.Anaeduslateralis , comb. nov.Anaedusottomerkli nom. nov., for Anaeduslateralis Pic, 1923: 16. Distribution: Vietnam. Secondary homonym of Anaeduslateralis [Spinolyprops]. Distribution: Myanmar, Thailand, Laos, Malaysia, and Indonesia.Anaeduspakistanicus , comb. nov.Anaedusthailandicus , comb. nov.Anaedustrautneri , comb. nov.Spinadaenus , comb. nov. Note that the type species Spinadaenussingularis Pic, 1921 is considered a junior subjective synonym of Lyprops [sic] serrimargo Gebien, 1914 , Sphingocorse and Pseudanaedus are distinguished from Anaedus by the shape of the pronotum. Again, the shape of the pronotum is not distinct and falls within the diversity of forms seen In Anaedus. We place Sphingocorse in synonymy with Anaedus, resulting in the following new combinations, and necessitating one new replacement name.rse Fig. , known f the eye . In his Anaedusangulicollis , comb. nov.Anaedusnepalicus , comb. nov.Anaedusmaculipennis , comb. nov.Anaedusschawalleri nom. nov. for Anaedusnepalicus Schawaller, 1994: 267. Distribution: Nepal. Secondary homonym of Anaedusnepalicus [Sphingocorse]. Distribution: Nepal.Aspisoma Duponchel & Chevrolat, 1841 (Coleoptera: Tenebrionidae) has a complicated taxonomic history, and although its synonymy with Anaedus was established by Aspisoma\u2019 was published in Aspisomafulvipenne Duponchel & Chevrolat, 1841. However, the authors failed to realize that the name \u201cAspisoma\u201d had already been published by Laporte (1833) for a genus of Lampyridae (Coleoptera), and thus Aspisoma Duponchel & Chevrolat, 1841 is a junior homonym of Aspisoma Laporte, 1833.Aspisoma\u201d which have long been confused in catalogs and checklists. Aspisoma Duponchel & Chevrolat (Tenebrionidae) and therefore included them within the genus Anaedus following Lacordaire\u2019s synonymy. However, Aspisoma Laporte (Lampyridae) where they have continued to be listed was included as a member of Anaedus by Several papers by e listed . One of Tenebrionidae. In each paper, the species are described between Anaedus and other genera which we here treat as synonyms . Furthermore, Anaedus. We have not seen any of these types but from the descriptions and arrangement in his works we are confident that Pic meant to place these species in Aspisoma Duponchel & Chevrolat (Tenebrionidae), though it is not clear if he merely missed Lacordaire\u2019s synonymy or truly intended to return the group to genus rank.All four of Pic\u2019s works indicate that the species were meant to be placed in Tenebrionidae: Lagriinae which leaves no western hemisphere species described by Pic remaining in Aspisoma Laporte (Lampyridae). The combinations are restored to Anaedus and results in the following nomenclatural acts:We recognize the following species as members of Anaedusboliviensis , comb. rest.Anaedusclaveri , comb. rest.Anaedusdiversicollis , comb. rest.Anaeduselongatus , comb. rest.Anaedusgrimmi nom. nov. for Aspisomaforticornis Pic, 1917b: 23. Distribution: Brazil. Secondary homonym of Anaedusforticornis [Lyprops]. Distribution: Indonesia. See Anaedusguyanensis , comb. rest.Anaedusholtzi , comb. rest.Anaedusinangulatus , comb. rest.Anaedusinhumeralis , comb. rest.Anaedusmendesensis , comb. rest.Anaedusminutus , comb. rest.Anaedusrufimembris , comb. rest.Anaedusrufipennis , comb. rest.Anaedussubelongatus , comb. rest.Anaedusminutus , comb. rest.Anaedusminimus nom. nov. for Anaedusminutus Pic, 1938: 16. Distribution: Vietnam. Secondary homonym of Anaedusminutus [Aspisoma] Distribution: Brazil.Anaedusmerkli nom. nov. for Anaedusdiversicollis Pic, 1938: 17. Distribution: Vietnam. Secondary homonym of Anaedusdiversicollis [Aspisoma]. Distribution: Guyana.Acropachia M\u00e4klin, 1875 [Tropical America] One species, pronotum with lateral pits. We would have to see type to confirm tribe and key placement.*Microgoniadera Pic, 1917a [Tropical America] One species, possibly another striate form of Anaedus.*Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffTribeLesne, 192632B08D71-F681-5B3D-A4C9-12C39B03C30ALuprops Hope, 1833.Body length: 5.2\u201311.2 mm; stout to elongate, glabrous or setose. Most species are unicolored but some are bicolored .Head: Eyes reniform, anteriorly notched by canthus, rarely completely divided. Antennae moderately long, usually reaching or slightly extending past base of pronotum; antennomeres obconical to moniliform.Thorax: Pronotum shape variable, quadrate to cordate, usually narrower than width of elytra. Lateral margins complete. Procoxae clearly separated by prosternal process. Mesocoxal cavity laterally closed, at least partially, by mesepimeron. Elytra striate. Metathoracic wings well developed or absent. Legs slender, not fossorial, penultimate tarsomeres lobed or cupuliform.Abdomen: Intersegmental membranes visible between sternites V\u2013VII, abdominal hinging tenebrionoid. Defensive glands present . The subtribes can be distinguished from Lupropini as follows. Lagriina is characterized by the terminal antennomere elongate in most species; prosternal process greatly reduced, resulting in the procoxae appearing to be nearly contiguous; pronotum lacks lateral carinae. Statirina is characterized by the terminal antennomere elongate in all species; prosternal process narrow or wide, clearly separating procoxae; pronotum has complete lateral carinae. Phobeliina is characterized by the terminal antennomere subequal to penultimate antennomere; prosternal process wide, clearly separating procoxae; pronotum lacks lateral carina. In contrast, Lupropini has terminal antennomere subequal to penultimate antennomere; prosternal process wide, clearly separating procoxae, pronotum with lateral carinae clearly developed, at least in anterior fourth.III Figs . This trCoxelinus Fairmaire, 1869, Curtolyprops Pic, 1917d, Dichastops Gerstaecker, 1871 and Luprops Hope, 1833.Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffGenusSchawaller, 20112D13EC55-F5C3-5CD5-96F9-510AE386E613CapelupropsCapeluproprslaenoides Schawaller, 2011. Schawaller, 2011: 271. Type species: Capeluprops Schawaller, 2011 is provisionally moved from Lupropini to Laenini. Capeluprops contains six species of small, litter-inhabiting, flightless tenebrionids restricted to southern South Africa to Laenini (Lagriinae). This genus contains a single species which occurs in high elevation arid regions around Lake Titicaca in Bolivia. Plastica in Apocryphini based on its apparent similarity to species in the genus Apocrypha Eschscholtz, 1831, but separated the two genera based on differences in the femora and tarsi. Apocrypha, as with all other members of Tenebrioninae, possess abdominal defensive glands that open between abdominal sternites VII and VIII.NHMUK provided by Dmitry Telnov and dissection of specimens matched with the holotype clearly place Plastica in Laenini. Plasticapolita does not possess abdominal defensive glands, excluding it from any lineages of Tenebrioninae. The following characters support its placement in Laenini: eyes small and round, not emarginate anteriorly in Lagriini. However, subsequent catalogus did not follow Matthews\u2019 assessment, and Phobelius is currently included within Goniaderini with Phobeliina similarly synonymized under this tribe . A third specimen from Costa Rica and seems to fall within the circumscription of Diaperinae to Leiochrinini Lewis, 1894 (Diaperinae). Falsotithassa contains ten species of small Tenebrionidae distributed across the Indo-Malayan biogeographic region. In the original description of this genus, Pic noted its similarity to Tithassa, which in this present paper is classified in Prateini. Based on the ordering of the descriptions in Falsotithassa between species of Anaedus (Goniaderini) and Tithassa, it can be inferred that Pic considered this genus to be closely related to these taxa, and therefore included in Lagriinae. Falsotithassa, providing a detailed diagnosis for this genus, and synonymized Derispiolina Kaszab, 1979 which was originally described as a tentative member of the tribe Leiochrinini , but in a later paper , a character that is only known to occur in Diaperini and Nilionini antennae with complex sensoria on antennomeres 4\u201311; (2) abdominal defensive gland reservoirs joined by lateral commissure; (3) female internal reproductive tract with large thin-walled spermathecae. Further support of this conclusion is provided by characters mentioned by Falsotithassa departs from the coccinellid-like appearance of all other current members of Leiochrinini and indeed is externally similar to members of Scaphidemini Reitter, 1922. The latter is presently defined by a strongly sclerotized T-shaped spermatheca and the defensive glands lacking a commissure and Cnodalonini (Stenochiini) . Due to Taxon classificationAnimaliaColeopteraTenebrionidae\ufeffTribeNabozhenko, Perkovsky & Nazarenko, 202310E3DC69-541C-508A-9A3D-BDE6546936F7Archaeoluprops Nabozhenko, Perkovsky & Nazarenko, 2023.Archaeolupropini Nabozhenko, Perkovsky & Nazarenko, 2023 is transferred from Lagriinae to Tetratomidae: Tetratominae Billberg, 1820. This tribe was recently described for a single beetle preserved in Eocene amber (Lagriinae where it was found to not belong to any of them, and therefore was placed into a new tribe in the subfamily. Examination of the descriptions and excellent photographs in that paper demonstrate that this taxon clearly belongs within the family Tetratomidae.The tribe ne amber . This beArchaeolupropsgroehni Nabozhenko, Perkovsky & Nazarenko, 2023 possesses the following characters consistent with Tetratomidae: the basal two ventrites connate with 3\u20135 articulated; antennal insertions visible from above; elongate and linear terminal maxillary palpomeres; vertical lateral aspect of the abdominal ventrites which fit beneath the elytra; paired depressions near the posterior pronotal margin; hind coxae elongate, not bounded laterally by the sides of the first abdominal ventrite. The images do not clearly show the procoxal closure, but it appears they could be open externally. The lack of elytral striae, shape of the scutellar shield, and general facies indicate that this species belongs in the nominate subfamily Tetratominae, though the available specimen does not allow for examination of antennal clubs or male genitalia which are the primary features currently used to separate tetratomid subfamilies (Archaeolupropini to Tetratomidae: Tetratominae and leave it there as a valid tribe in that subfamily pending further revision.families . Based uLagriinae are summarized in Table A list of the proposed changes from the current positions of pertinent genera within"} +{"text": "Cibotium barometz is the original plant of cibotii rhizoma (\u201cGouji\u201d), a traditional Chinese medicine used in the therapy of pain, weakness, and numbness in the lower extremities. Long-history medicinal use has caused serious wild population decline in China. Without sufficient understanding of the species and lineage diversity of Cibotium, it is difficult to propose a targeted conservation scheme at present, let alone select high-quality germplasm resources. In order to fill such a knowledge gap, this study sampled C. barometz and relative species throughout their distribution in China, performed genome skimming to obtain plastome data, and conducted phylogenomic analyses. We constructed a well-supported plastome phylogeny of Chinese Cibotium, which showed that three species with significant genetic differences are distributed in China, namely C. barometz, C. cumingii, and C. sino-burmaense sp. nov., a cryptic species endemic to NW Yunnan and adjacent regions of NE Myanmar. Moreover, our results revealed two differentiated lineages of C. barometz distributed on the east and west sides of a classic phylogeographic boundary that was probably shaped by monsoons and landforms. We also evaluated the resolution of nine traditional barcode loci and designed five new DNA barcodes based on the plastome sequence that can distinguish all these species and lineages of Chinese Cibotium accurately. These novel findings on a genetic basis will guide conservation planners and medicinal plant breeders to build systematic conservation plans and exploit the germplasm resources of Cibotium in China.Germplasm resources are the source of herbal medicine production. The cultivation of superior germplasm resources helps to resolve the conflict between long-term population persistence and growing market demand by consistently producing materials with high quality. The fern species Artemisia annua L. C. Y. Yang Trevis in many studies, Panax notoginseng (Burk.) F. H. Chen J. Sm. is the original species . Phytochsurvival .C. barometz is listed in Appendix II of CITES (https://cites.org/eng/app/appendices.php), and the genus Cibotium is listed in the Grade II Category of the List of National Key Protected Wild Plants of China comprises ca. 9\u201312 species distributed in tropical and subtropical regions of Asia, Central America, and the Hawaiian Islands has been widely utilized for phylogenetic reconstruction at different levels as well as species delimitation of closely related species in recent years fragments have been applied to the phylogenetic construction of the tree fern clade, including Cibotium . Howeverrs e.g., . Therefobarcodes , which lbarcodes .C. barometz and relatives throughout the distribution range in China and adjacent areas. We aimed to 1) compare structure and composition variations of plastomes among Chinese Cibotium species; 2) propose a phylogeny-based species delimitation; 3) investigate the geographical pattern of variation of C. barometz based on plastome data; and 4) suggest candidate barcodes for specific species and lineage identification of Chinese Cibotium. We believed that our findings would benefit the conservation and breeding of this important medicinal plant taxon and provide insights into the systematics and evolution of ferns.In this study, we performed genome skimming and assembled complete plastomes of representative samples of Cibotium individuals were collected for genome skimming sequencing throughout the distribution range of China and adjacent regions . Total genomic DNA was extracted with a modified CTAB procedure . Libraride novo assembled plastomes of all our samples with clean reads using the GetOrganelle toolkit , as well as three outgroup species from the tree fern clade, i.e., Alsophila spinulosa (NC_012818), Sphaeropteris brunoniana (NC_051561), and Plagiogyris euphlebia (NC_046784), were aligned with MAFFT v.7.313 and concatenated all these single gene alignments to build a protein-coding gene dataset for phylogenetic analyses. The best-fitting nucleotide substitution models of the full-length and protein-coding gene alignments were determined as TVM + F + G4 and GTR + F + G4, respectively, based on the Bayesian information criterion (BIC) by ModelFinder applied in previous studies and lower GC content (41.4%). The length of LSC and SSC is rather stable among all accessions, whereas IR size varies among samples of C. cumingii , most C. barometz , and those Yunnan\u2013Myanmar samples with clearly no difference. The boundaries of IRs are the same among all samples, without any expansion or contraction. In comparison, the intergeneric region between rrn16 and rps12 varies greatly among species because of an early termination resulting from the missing one or two nucleotides due to a codon shift mutation in the reference plastome of C. barometz , and three protein-coding genes are totally duplicated, whereas ndhB and rps12 have only one incomplete duplication.All the plastomes encode a total of 117 unique genes in identical order, including 85 protein-coding genes, 28 tRNA genes, and four rRNA genes . In mostC. cumingii, most C. barometz, as well as the five \u201cC. barometz\u201d samples from NW Yunnan and NE Myanmar. The clade formed by the five Yunnan\u2013Myanmar samples and the Ryukyu Islands, and Subclade W, including samples from SW China . The Hainan sample clustered within Subclade E based on the protein-coding gene dataset with low support value of the nine traditional cpDNA loci are effective in the identification of C. cumingii, while only the first two of the four could further discriminate Yunnan\u2013Myanmar Cibotium correctly. None of them accurately depicted the intraspecies divergence within C. barometz. We also tested the concatenated dataset of trnL-trnF, trnG-trnR, rps4-trnS, and rbcL-accD and found poor resolution among all C. barometz, including those Yunnan\u2013Myanmar samples . We checked the spores of C. sino-burmaense and found they shared similar perine features with the two known Chinese species photographed by C. barometz from S. China (30\u201345 \u03bcm). Because larger spore size is an indicator of higher ploidy levels in some fern taxa , which may lead to inbreeding, affect adaptive potential, facilitate the accumulation of deleterious mutations, and finally hinder the long-term survival of species than those on the acroscopic side; apex of pinnule segments acute; sori oblong to spherical, usually 4\u20138 and sometimes over 10 pairs per pinnule segment; average exospore equatorial diameter more than 45 \u03bcm...............................................................2.\u00a0C. cumingii1b. Pinnules on basiscopic side of lower pinnae usually three lacking; sori usually one or two per pinnule segment...................................................................3.\u00a0Cibotium barometz (L.) J. Sm., London J. Bot. 1 (1842) 437.(1) Polypodium barometz L., Sp. Pl. 2 (1753) 1092.\u2261 Aspidium barometz (L.) Willd., Sp. Pl., ed. 4 [Willdenow] 5 (1810) 268.\u2261 Nephrodium barometz (L.) Sweet, Hort. Brit. [Sweet], ed. 2. (1830) 580.\u2261 Dicksonia barometz (L.) Link, Fil. Spec. (1841) 166.\u2261 W.T. Tsang 22473 (S No. S14-33459 [image!])Neotype (designated by Mazumdar in Nordic J. Bot. 34(4): 465. 2016): \u2014China. Guangxi, SE of Shang-sze (Shangsi) District, Shap Man Taai Shan (Shiwandashan), near Hoh Lung village, 16 Jun 1933, Balantium glaucescens Link, Fil. Spec. (1841) 40.= Type: \u2014Not designated.Cibotium glaucescens Kunze, Farnkr\u00e4uter 1 (1841) 63, t.31.= Type: \u2014Not designated.= Cibotium assamicum Hook., Sp. Fil. [W. J. Hooker] 1 (1844) 83, t.29B.Mrs. Mack s.n. (not traced).Holotype: \u2014India. Assam, Dicksonia assamicum Griff., Notul. 2 (1849) 607.= Griffith s.n. (K barcode K001090393 [image!]).Lectotype (designated here): \u2014India. Assam, Cibotium djambianum Hassk., Fil. Jav. 1 (1856) 61.= Type: \u2014Not designated.Distribution: \u2014China , Japan (Ryukyu Islands), Indonesia (Java to Sumatra), Malaysia, Myanmar, Thailand, Vietnam.Cibotium sino-burmaense X.C. Zhang & S.Q. Liang, sp. nov. ((2) C. barometz and C. cumingii, differing from the former in the significantly shortened pinnule length on basiscopic side, as well as acute apex and more sori of pinnule segments, and from the latter in the denser sori per pinnule segment and presence of the second and third pinnules on the basiscopic side of lower pinnae.Diagnosis: \u2014This new species resembles X.C. Zhang 12880 (PE!).Holotype: \u2014China. Yunnan: Gongshan county, Dulongjiang Township, 2 May 2022, Note: \u2014The holotype consists of a single large frond mounted on fifteen herbarium sheets, labeled \u201csheet 1\u201d to \u201csheet 15\u201d.Description: \u2014Rhizome prostrate, stout, densely covered with shiny yellowish brown long hairs. Stipes thick, up to 80\u00a0cm or more, dark brown to purplish black at base and becoming green upwards, covered with long hairs similar to those on rhizome at base, upper part covered with small, appressed flaccid hairs. Lamina ovate, 2-pinnate-pinnatifid, up to 3\u00a0m, subleathery, adaxial surface deep green, abaxial surface glaucous, with small flaccid hairs on midrib; pinna 8\u201310 pairs, alternate, stalked, medial pinnae 60\u201380 \u00d7 20\u201330 cm, basal pinna pairs reduced slightly; pinnules more than 30 pairs per lower pinna, shortly stalked, up to 20\u00a0cm on the acroscopic side, 10-14\u00a0cm on the basiscopic side; pinnule segments, alternate, slightly falcate, with acute apex, margins crenulate to serrulate-serrate. Sori oblong to spherical, usually 4\u20138 and sometime over 10 pairs at base of lower pairs of pinnule segments; indusia bivalvate, outer indusia larger, orbicular, inner significantly smaller, oblong. Spores pale yellowish, with strongly developed equatorial and distal ridges.Sino-burmaense is derived from the known distribution of this species along China\u2013Myanmar border.Etymology: \u2014X.C. Zhang & al. 8134; Fugong County, 26 April 2022, X.C. Zhang 12831. Myanmar. Kachin: Htawgaw, April 1925, G. Forrest 26496 .Additional Specimens Examined: \u2014China. Yunnan: Gongshan county, Dulongjiang Township, 23 Jan 2017, Distribution and habitat: \u2014China (NW Yunnan), Myanmar (Kachin). On cliff with open canopy.Cibotium cumingii Kunze, Farrnkr\u00e4uter 1 (1841) 64, 65.(3) Cibotium barometz var. cumingii (Kunze) C. Chr., Index Filic. 3 (1905) 183.\u2261 H. Cuming 123 .Lectotype (designated here): \u2014Philippines. Luzon, Cibotium crassinerve Rosenst., Meded. Rijks-Herb. 31 (1917) 4.= H. M. Curran & M. L. Merritt 15800 .Lectotype (designated here): \u2014Philippines. Luzon, Benguet, Dec 1908, Cibotium taiwanense C. M. Kuo, Taiwania 30 (1985) 56, 57.= C. M. Kuo 1703 .Lectotype (designated here): \u2014China. Taiwan, Hsinchu, Chu-tong, August 1972, Distribution: \u2014China (Taiwan), Japan (Ryukyu Islands), Philippines.Cibotium from China. Based on phylogenomic analyses, we constructed a well-supported phylogeny of Chinese Cibotium and indicated that there are three species distributed in China, namely C. barometz, C. cumingii, and C. sino-burmaense, an overlooked cryptic species from NW Yunnan and NE Myanmar. Moreover, our results uncovered the east-west lineage divergence in C. barometz. We also evaluated the species resolution of nine old cpDNA loci and suggested five new cpDNA barcodes that are capable of identifying all the above-mentioned species and lineages of Chinese Cibotium accurately. In conclusion, our findings will improve people\u2019s understanding of the germplasm resource diversity of this endangered medicinal plant group and play a guiding role in its wild population conservation and medical value exploitation.This study presents the conserved structure and gene composition of the chloroplast genome within https://www.ncbi.nlm.nih.gov/genbank/, OQ721080-OQ721104.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: X-CZ, K-XL and R-HJ designed this study. FW, L-MT, BQ, Y-YC and Y-HH collected and cultivated plant materials of this study. S-QL performed experiments, analyzed the data, and wrote the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "Potamonautesamatholesp. nov., is described from the Winterberg-Amathole mountain range in the Eastern Cape Province, South Africa. Morphologically, P.amathole Peer & Gouws, sp. nov. most closely resembles P.tuerkayi but can be distinguished by key morphological characters including the variation in the shape of the subterminal segment of gonopod 2 between both species. Genetically, P.amathole Peer & Gouws, sp. nov. is placed within the clade of small-bodied, mountain-dwelling crabs including P.parvispina, P.parvicorpus, P.brincki, P.tuerkayi, P.baziya, and P.depressus. The new species is found in slow-moving mountain streams and pools at high altitudes. The continued discovery and description of new freshwater crab species reinforces the need for ongoing research, especially in under-sampled regions.A new species of freshwater crab, Potamonautes and Maritimonautes represent the freshwater crabs with a total of 26 described species since the last published descriptions , following the manufacturer\u2019s protocol.2, 0.2 mM deoxynucleotide triphosphate (dNTP), 0.2 \u00b5M of each primer, and 0.5 U Taq polymerase. The thermocycling profile included an initial denaturing at 95 \u00b0C for 5 min, 30 cycles of 95 \u00b0C for 45 s, 45 \u00b0C for 45 s and 72 \u00b0C for 1.5 min, followed by a final extension of 72 \u00b0C for 5 min. Amplification was confirmed by gel electrophoresis in a 0.5% agarose gel stained with SYBR Green and viewed with a UV-transilluminator. PCR products were purified with an Invisorb PCRapace Quick purification kit (Invitek Molecular). Purified products were cycle-sequenced in both forward and reverse directions using the ABI Big Dye Sequencing kit v. 3.1. . Cycle-sequencing products were precipitated using a NaAc-ethanol procedure gene was amplified and sequenced using the approach described by In the second study, DNA was extracted from specimens collected from Hogsback during 2018, using a PureLink Miniprep kit . A fragment of the protein-coding mtDNA cytochrome Potamonautes species, as compiled previously was included for P.brincki; unfortunately, no other 16S sequence was available. The P.lividus specimen from Eswatini (formerly Swaziland) included in the study by P.valles , P.mariepskoppie , P.ngoyensis , P.ntendekaensis and P.mhlophe . In a recent systematic revision, Potamonautes species included by Arcopotamonautes , Maritimonautes and Rotundopotamonautes (R.ohdneri and R.subukia). The representatives of Maritimonautes were used as outgroups in the present study, due to their basal placement relative to Potamonautes analyses, as implemented in PAUP*4.0a168 , with values above 0.95 being regarded as evidence of support. These were generated through Bayesian inferences as described in ClustalX2 was used*4.0a168 . Prior t*4.0a168 , with moMorphological variables were measured using a pair of Vernier callipers. A Canon Powershot G12 digital camera was used to photograph carapaces and appendages, while a Nikon SMZ25 microscope fitted with a Nikon Digital Sight DS-Fi2 camera was used for macro-examination and to take photos of gonopods and mouthparts.ISAMIziko South African Museum, Cape Town, South Africa;EC Eastern Cape;WC Western Cape;KZN KwaZulu\u2013Natal.Abbreviations for all morphological and morphometric characters ;s3/s4 Second sternal groove (suture between the third and fourth sulci).OQ559329\u2013OQ559337; COI: OQ558909\u2013OQ558911). The 16S alignment was 549 nucleotides in length. The ML analysis, using the parameters of the optimal model , produced the topology (-lnL = 3754.743) presented in Fig. New sequences generated in the present study were lodged in GenBank and a gamma distribution of rate variation (\u03b1 = 1.280). The tree produced by the ML analysis is shown as Fig. The COI alignment was 660 nucleotides in length. The optimal model had base frequencies of A = 0.292, C = 0.184, G = 0.154 and T = 0.371, a rate matrix of RPotamonautes radiation , P.clarus Gouws, Stewart & Coke, 2000, P.depressus , P.parvicorpus Daniels, Stewart & Burmeister, 2001, P.parvispina Stewart, 1997 and P.tuerkayi Wood & Daniels, 2016; a clade of robust, large-bodied riverine species i.e. P.barbarai Phiri & Daniels, 2014, P.barnardi Phiri & Daniels, 2014, P.bayonianus , P.dentatus Stewart, Coke & Cook, 1995, P.granularis Daniels, Stewart & Gibbons, 1998, P.perlatus , P.sidneyi Rathbun, 1904, P.unispinus Stewart & Cook, 1998 and P.warreni Calman, 1918); a clade of species largely inhabiting forests in the Indian Ocean Coastal Belt (IOCB) ; and a clade of mostly burrowing IOCB or tropical highland species with P.flavusjo Daniels, Phiri & Bayliss, 2014, P.mariepskoppie Daniels, Barnes, Marais & Gouws, 2021, P.mulanjeensis Daniels & Bayliss, 2012, P.mutareensis Phiri & Daniels, 2013, P.ngoyensis Daniels, Busschau & Cumberlidge, 2019 and P.ntendekaensis Daniels, Busschau & Cumberlidge, 2019. Discrepancies between the two topologies concerned the placement of P.dentatus and P.mhlophe Daniels, 2017 of mountain-dwelling species from the Western Cape , which was sister to a clade containing those from the Drakensberg in the Eastern Cape and KwaZulu-Natal. Other samples from Hogsback, including one collected sympatrically with the aforementioned at the Hogsback Arboretum, were allied to P.danielsi within the clade of IOCB forest-dwelling species with high support (BPP 1.00). In the COI topology, where only samples from Hogsback were included, these were placed similarly within the clade of mountain-dwelling species. These results suggest the presence of two distinct species among the crabs sampled from Hogsback and Katberg.Of relevance to the current study, the crabs sampled from Hogsback and Katberg were placed in two separate clades. In the 16S topology, samples from Hogsback and Katberg were placed within the clade of small-bodied, mountain-dwelling species, sister to P.danielsi. Given their close affinity and the general trends in terms of sequence divergence, and the strong support (BPP = 1.00) for the clade formed by these specimens and P.danielsi, it is considered that these are conspecific. The Hogsback and Katberg specimens within the mountain-dwelling clade were 5.4 to 8.9% divergent from the other species in this clade and were 5.8 to 8.3% divergent from their sister-taxon (P.parvispina). In the context of the above divergences among known species, the Hogsback and Katberg specimens in this clade are considered to be a distinct species, described below. The Hogsback specimens were also 7.6\u20138.0% divergent from those collected in sympatry or near-sympatry but belonging to the IOCB clade.Uncorrected sequence divergences among individuals are presented in Suppl. material P.barbarai and P.granularis (0.5%), previously described species were 2.4 to 18.4% divergent. Comparatively, these divergences again support the taxonomic distinctiveness of the Hogsback specimens.For the COI data, where the only specimens included from Hogsback belonged to the clade of mountain-dwelling species, uncorrected sequence divergences between these specimens and other species in that clade ranged from 7.4 to 10.9%. With the exception of the comparison between Potamonautes\ufeffGenus Taxon classificationAnimaliaDecapodaPotamonautidae\ufeffPeer & Gouwssp. nov.0FDA1948-A61F-5785-B804-4500713FA65Bhttps://zoobank.org/E47B3AFA-479B-496E-B7E3-F1F13849CEC2Holotype: male, CL = 25.3 mm , 25 October 2018, L. Maliwa, N. Miranda and N. Peer legit (MB-A094813). Allotype: female, CL = 24.9 mm ; 32\u00b036'24.4\"S, 26\u00b057'48.2\"E, elevation 1092 m, 24 October 2018, L. Maliwa, N. Miranda and N. Peer legit.Potamonautesamathole sp. nov. exhibits a smooth carapace, flank and epibranchial region, with a rounded anterolateral margin and a narrow posterior end. Postfrontal crest complete. Dactyl of major cheliped highly arched. Pereopod 4 is longest. Bi-lobed maxillary palp with no flange.Carapace . Branchial region rounded. Anterior margin straight, lying on same horizontal plane as anterolateral margin; anterolateral margin slightly granulated. Urogastric grooves well-defined; cardiac and cervical grooves well-defined where attached to urogastric groove, becoming poorly defined and shallow towards edge of carapace. Epigastric lobes well-defined by two indentations forked from midpoint of postfrontal crest. Postfrontal crest complete, straight, and distinct, curving down at epibranchial region, sloping backwards to join anterolateral margin. Exorbital teeth present. Epibranchial teeth absent. Carapace brown with orange-brown to purple-brown limbs when alive.ace Fig. . CephaloSternites prominent across sternum and third sulcus (s3/s4) complete, deep, projecting down medially towards abdomen.tes Fig. . SternitThird maxilliped . Dactyl of major chela highly arched, large interspace formed in major cheliped when fingers closed, slim interspace formed when minor cheliped closed. Propodus fairly slim (CRPW/CRPL = 0.41), exhibiting 17 cutting teeth on major dactyl and 15 cutting teeth on pollex, some larger and more prominent. Carpi on either side with one prominent tooth and two rudimentary teeth. Meri granulated with spine on anterior surface. Slender pereopods , pereopod 4 longest, pereopod 5 shortest. Ventral margins of propodi smooth, dorsal margins bearing fine serration, dactyli serrated, ending in sharp points.ods Figs , 5a, b. Pleon , P.parvispina Stewart, 1997, P.parvicorpus Daniels, Stewart & Burmeister, 2001, and P.tuerkayi Wood & Daniels, 2016. Morphologically, the species can be most easily distinguished from P.parvispina by the latter\u2019s small but pronounced epibranchial tooth. Potamonautesparvicorpus bears slightly arched chelipeds, an arched carapace, and a poorly developed postfrontal crest, while the new species has highly arched major chelipeds, a flattened carapace and a distinct postfrontal crest. Potamonautesbrincki also has an arched carapace as well as a partitioned terminal segment of the mandibular palp with a setae-covered flange. Potamonautesamathole sp. nov. has a unilobed terminal segment of the mandibular palp with no flange. Of all the Western Cape montane freshwater crabs, P.tuerkayi is the most similar to P.amathole sp. nov. However, P.tuerkayi has a sharply tapering subterminal segment of gonopod 2, forming a rounded subterminal base, while in P.amathole sp. nov. this tapering is gradual, forming a sloping instead of a rounded base. Geographically, the above-mentioned species are all confined to the Cape Fold Mountain region, with P.amathole sp. nov. being the first described small-bodied montane freshwater crab from the Eastern Cape part of the Great Escarpment.Potamonautesdepressus and P.clarus are two species of highland river crabs in the Drakensberg Mountain range. Although superficially similar to P.amathole sp. nov. in terms of a flattened carapace and slender limbs, morphological differences do exist in the structure of the mandibular palp and carapace depression. In P.clarus, a bright orange species, the mandibular palp has a flange on the terminal segment, while this is absent in P.amathole. Potamonautesdepressus has an extremely flattened carapace, with CH/CL ranging from 0.38\u20130.43. In P.amathole sp. nov., this depression of the carapace is less extreme with a ratio ranging from 0.43\u20130.51. Both of these species are confined to fast-flowing rivers in the Drakensberg highlands. In most other Potamonautes spp., pereopod 3 is the longest. However, in P.amathole sp. nov., pereopod 4 appears to be the longest.Afrocarpusfalcatus, Celtisafricana, Calodendrumcapense, Veprislanceolata, and Zanthoxylumdavyi (Hogsback and Katberg are both situated in the Keiskamma River catchment. Both sites consist of Southern Mistbelt Forest (FoZ 3), known to be tall, multi-layered, species-rich forests dominated by lumdavyi . Within lumdavyi .Ephemeroptera, Coleoptera, Hemiptera, Diptera, Trichoptera, Odonata, and Plecoptera Waterfall site is situated inside the Hogsback State Forest. The habitat is represented by a tall, high-flowing stream with different biotopes and pools rich in macro-invertebrate diversity, i.e., ecoptera . The subPseudoschoenusinanis) with tree canopy cover and burrows . The indication of the P.danielsi Hogsback population, alongside the morphological identification of the specimen used in a study by P.danielsi . In KZN, two montane freshwater crabs, i.e., P.clarus and P.depressus, together with P.baziya represent the Drakensberg Escarpment species, with all three being closely related. In the Western Cape, P.parvispina, sister species to P.amathole sp. nov., is located within the Cederberg region. P.brincki, P.tuerkayi, and P.parvicorpus, and found an east/west separation defined by the Cape Fold Mountains. The results from this study and that of P.amathole sp. nov. diverged before the separation of the Cape Fold montane species. Several routes of palaeo- and current connectivity along the Great Escarpment have been demonstrated for floristic species (Although South African freshwater crabs have been extensively researched, we continue to find and describe new species , 2022. T species with Gal species and ephe species , althoug"} +{"text": "Following publication of the original article [1], in this article ref. 5 and 13 was incorrect and should have been read as follow:5. Alexander D, Eustace-Cook J, Brenner M. Approaches to the initiation of life-sustaining technology in children: a scoping review of changes over time. J Child Health Care. 2021;25(4):509\u201322. 10.1177/1367493520961884.13. Alexander D, Quirke M, Berry J et al. Initiating technology dependence to sustain a child\u2019s life: a systematic review of reasons. J Med Ethics. 2021. 10.1136/medethics-2020-107099.The original article has been corrected."} +{"text": "Glycosylation is an important protein modification, which influences the physical and chemical properties as well as biological function of these proteins. Large-scale population studies have shown that the levels of various plasma protein N-glycans are associated with many multifactorial human diseases. Observed associations between protein glycosylation levels and human diseases have led to the conclusion that N-glycans can be considered a potential source of biomarkers and therapeutic targets. Although biochemical pathways of glycosylation are well studied, the understanding of the mechanisms underlying general and tissue-specific regulation of these biochemical reactions in vivo is limited. This complicates both the interpretation of the observed associations between protein glycosylation levels and human diseases, and the development of glycan-based biomarkers and therapeutics. By the beginning of the 2010s, high-throughput methods of N-glycome profiling had become available, allowing research into the genetic control of N-glycosylation using quantitative genetics methods, including genome-wide association studies (GWAS). Application of these methods has made it possible to find previously unknown regulators of N-glycosylation and expanded the understanding of the role of N-glycans in the control of multifactorial diseases and human complex traits. The present review considers the current knowledge of the genetic control of variability in the levels of N-glycosylation of plasma proteins in human populations. It briefly describes the most popular physical-chemical methods of N-glycome profiling and the databases that contain genes involved in the biosynthesis of N-glycans. It also reviews the results of studies of environmental and genetic factors contributing to the variability of N-glycans as well as the mapping results of the genomic loci of N-glycans by GWAS. The results of functional in vitro and in silico studies are described. The review summarizes the current progress in human glycogenomics and suggests possible directions for further research. Glycans, also known as poly- or oligosaccharides, are polymersconsisting of monosaccharides joined together byglycosidic linkages. Glycans may covalently bind to proteinsand lipids by glycosidic bonds to produce glycoproteins andglycolipids, respectively. Glycosylation is one of the mostcommon post- and co-translationalprotein modifications. It is found that about 20 % of allproteins in nature are glycosylated .Meanwhile, over 40 % (by weight) of all proteins in humanblood plasma are N-glycosylated . Glycosylationaffects not only physical and chemical propertiesof proteins, such as solubility, spatial configuration, folding,etc. ,but their biological function as well. Glycoconjugates, i. e.glycoproteins and glycolipids with covalently bound glycans,are present in cells of all multicellular organisms.Glycoproteins and glycolipids at the surfaces of cell membranesare involved in various cellular interactions, includingcell-cell, cell-extracellular matrix, and cell-macromoleculeinteractions, as well as interactions between organisms ,which plays a major part in development and functioning ofmulticellular organisms .Numerous studies into the chemical structure of glycansand their metabolism have been carried out in the early 20thcentury. At the time, however, glycans were primarily consideredas structural elements and energy sources for livingsystems. An explosive development of chemical, physical,and molecular biological methods in glycan research hasgiven birth to a new branch of molecular biology calledglycobiology. This domain includes studies of chemicaland physical properties of glycans, enzymology of glycansynthesis and degradation, their evolution, mechanisms ofglycan recognition by proteins, and the role of glycans infunctioning of biological systems, development of humandiseases and biological traits, as well as development ofnew methods for management, prophylaxis, diagnostics, andprediction of diseases . Today, glycobiologyis a rapidly developing science, and its findings are of greatsignificance for many related fields, including biomedicineand biotechnology .Similarly to genomics, transcriptomics, proteomics, andmetabolomics, glycomics is a systematic investigation intoglycome, i. e. a variety of all glycans and their contents in agiven specimen, whether it be a cell culture, tissue, organ,or the whole organism. The diversity of possible glycoconjugatesis beyond imagination. Although the number of monomersincorporated into glycan structure is relatively small,monomers may form various glycosidic bonds to create anabundance of possible glycans. The diversity of glycoconjugatesis further increased due to the possibility of a proteinhaving not one, but several glycosylation sites.In the early XXI century, high-throughput physical andchemical methods were developed, which made it possible tocarry out large-scale cohort studies to discover the associationsbetween N-glycome and human diseases and biologicaltraits. Currently, the associations of N-glycans with manymultifactorial diseases in humans , including type 2diabetes and monogenic forms of diabetes , rheumatoid arthritis, the Parkinson\u2019s disease , inflammatory bowel disease , as well as cardiovascular and oncologicaldiseases , have been identified.The results of observational studies of the associationsbetween protein glycosylation and human diseases do notshed a light on cause-and-effect relationships between themand molecular biological mechanisms underlying these relationships.From 1983 onward, there have been a numberof studies into the functional consequences of changes inprotein glycosylation .Glycosylation of immunoglobulin G (IgG) appears to bethe most deeply studied in this regard, due to its importancefor adaptive immunity. The IgG molecule has a conservedglycosylation site Asn297, located in the conserved domainCH2 of the heavy chain. This domain plays a major partin binding to Fc\u03b3 receptors, which in turn affects the effectorfunction of IgG. It was shown that a decrease in IgGfucosylation level intensified antibody-dependent cellularcytotoxicity . The further crystallographyinvestigation demonstrated that the lack of IgG fucosylationled to higher affinity between the Fc domain of IgGand the receptor Fc\u03b3RIIIA, while the presence of fucose inIgG glycanresulted in steric hindrances during the interactions.Given the above, a conclusion can be made about thefundamental importance of glycosylation research for theproblems of diagnostics, prediction, prophylaxis, and managementof human diseases. In 2012, the National Academy of Sciences of the United States presented a report onthe necessity of a large-scale glycome study, the reasoningbeing that glycans are directly involved in pathogenesis ofalmost all the known diseases .Carbohydrates are among the main groups of macromoleculesidentified in biology, along with proteins, lipids, andnucleic acids. The polymerization ability and a large numberof chiral atoms allow monosaccharides to form a largevariety of stereo- and regioisomers. Four main groups ofcarbohydrates are determined based on the degree of polymerizationas follows: monosaccharides , disaccharides , polysaccharideswith repeating units forming linear or branching compounds, andglycans, i. e. complex oligosaccharides with non-repetitiveunits, which can be free or bound to proteins or lipids .Protein-bound glycans are in turn divided into N-, O-,and C-glycans. N-glycans form a glycosidic bond to thenitrogenatoms (N) of asparagine amino acid; O-glycans \u2013 tothe hydroxyl groups of serine and threonine amino acids,and C-glycans \u2013 to carbon atoms of the tryptophan aminoacid. C-glycosylation is rarely observed compared to N- andO- glycosylation .An important difference between N- and O-glycosylationis that the N-glycosydic bond only forms with the asparagineof the Asn-X-Ser/Thr motif, where \u201c\u0425\u201d may representany amino acid, except for proline, whereas no such motifis known for O-glycans. In addition, there is a PNGaseF enzyme that specifically cleaves the N-glycosydicbond between a glycan and a protein, which leads to the releaseof N-glycans into solution for further analysis . As opposed to N-glycosylation, O-glycosylation sitedoes not have a consensus sequence, and the available methodsfor O-glycan isolation (beta elimination) show lowerspecificity compared to that for N-glycans . It is part of the reason why technologies and protocolsof glycan structure identification and high-throughputanalysis are currently more refined for N-glycans, which are thesubject matter of this survey.The most common monomers in N-glycans include monosaccharides,such as mannose, fucose, galactose, N- acetylglucosamine(GlcNAc), and N-acetylneuraminic acid. N-glycan structure always includes a backbone(Man\u03b11-3(Man\u03b11-6)Man\u03b21-4GlcNAc\u03b21-4GlcNAc\u03b21-Asn-X-Ser/Thr) the other monomers bind to by glycosidiclinkages. Glycans may have a branching structure withone or more branches called antennae. Monomers, such asgalactose, N-acetylneuraminic acid, or fucose, can bind toany of the antennae. Fucose can also bind directly to thebackbone. Negatively charged N-acetylneuraminic acid isthe only monomer in N-glycans that carries a charge. Theglycansnot containing N-acetylneuraminic acid are neutrally charged. N-acetylneuraminic acid in N-glycans is alwaysbound to a galactose residueThe Oxford glycan notation, one of the most commonlyused glycan nomenclatures , operatesas follows:1. The letter \u201cF\u201d at the very beginning of the name indicatesthe presence of fucose bound to the backbone2. It is followed by the \u201cAN\u201d sequence, where N is thenumberof antennae (branches) in the glycan structure.3. Then, if the sugar backbone is bisected, the letter \u201cB\u201d(bisecting) is added.4. If antennary branches are fucosylated, the letter \u201cF\u201d isadded.5. If the glycan structure includes galactose bound to one orseveral antennae, then the sequence GN follows,where N is the number of galactose residues in a glycan,and n1 indicates the carbon atom of galactose, with whichglycosidic bond is formed.6. If the glycan structure includes N-acetylneuraminic acidbound to one or several antennae, then the sequenceSN follows, where N is the number of N-acetylneuraminicacid residues in a glycan, and n1 indicatesthe carbon atom of N-acetylneuraminic acid, with whichglycosidic bond is formed.For example, the designation FA2 shows the presence of afucose residue bound to the backbone and two antennae in theglycan structure. The designation A3BG3S1 shows that glycanstructure includes three antennae, sugar backbone bisection,three-antenna galactosylation, and one-antenna sialylationAs opposed to mRNA and proteins encoded in the genomicDNA sequence and synthesized as a result of matrix processes,a glycan structure is not encoded in the genomedirectly, and its biosynthesis is a branching network ofbiochemical reactions . The finalstructure of a glycan is determined by the interaction of amultitude of molecules and factors, including substratesand their accessibility, the enzyme activity associated withglycan biosynthesis and degradation, their localization andcompetition for substrate, and transport proteins . It was also shown that structure and diversity ofN-glycans present in specific cells and tissues is partiallyregulated at the level of gene transcription encoding theproteins involved in glycan synthesis and degradation .Glycan biosynthesis occurs in the endoplasmic reticulum(ER) and Golgi apparatus (GA). The KEGG databasecurrently includes the data on over 300 enzymes involvedin glycan synthesis and degradation processes . Glycosyltransferases transporting activatedmonosaccharides to growing glycans are among the keyenzymes directly involved in N-glycan biosynthesis. Thededicated CAZy database providesannotation and classification for over 200 glycosyltransferases,at least 40 of them associated with the proteinN-glycosylation pathway.In addition, K.S. Egorova et al.developed the CSDB_GT database including the experimentally confirmed CAZy activities.N-glycan biosynthesis stages and the respective glycosyltransferasegenes are described in detail in surveys .Rapid development of glycobiology combined with the hugesuccess of epidemiological population studies boosted thedevelopment of high-throughput glycome profiling methodsfor blood plasma proteins. In the recent decade, several highthroughputN-glycome profiling methods have been developed, specifically high and ultra-highperformance liquid chromatography (HPLC and UHPLC),multiplex capillary gel electrophoresis with laser-inducedfluorescence detection, (xCGE-LIF), liquid chromatographyelectrospray mass spectrometry (LC-MS), matrix-assistedlaser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS). Representative N-glycosylation profilesof human blood plasma proteins obtained using threedifferent methods are presented in Fig. 2.A detailed comparison of the five most common N-glycomeprofiling methods for human blood plasma proteinsis presented in the review . Despitethe differences in technologies, all these methods includeseveral key stages, such as sample preparation , N-glycan isolation (for exampleby cleaving from glycoconjugates), separation of N-glycansand content measurement .Each of these glycan analysis methods has its advantagesand shortcomings. UHPLC and xCGE-LIF are used to analyzeglycans cleaved from proteins, while MALDI-TOF-MSand LC-MS based on mass spectrometry make it possible toanalyze glycopeptides with the protein regions containingcovalently bound glycans, which provides valuable informationon glycosylation of specific proteins. Compared toUHPLCand xCGE-LIF, MALDI-TOF-MS and LC-MSperform better with regard to distinguishing glycans withdifferent molecular weights, but are unable to distinguishglycan stereoisomers. UHPLC and xCGE-LIF provide moreaccurate quantitative estimates due to their high resolution.In addition, they are characterizedby high performance andlower initial costs compared to the methods based on massspectrometry.UHPLC has turned out to be the most popular highthroughputN-glycome profiling method for blood plasmaproteins among the listed above dueto its relative cheapness, improved resolution (compared toHPLC), and high performance. By the time this review wascomposed (October 2022), human blood plasma glycomehad been studied in about 200,000 samples all over theworld, with about 80 % of the samples studied using UHPLC.By the early 2010s, the development of high-throughputglycomeprofiling and genetic analysis methods had made itpossible to carry out the first research efforts in genetic controlof glycosylation based on the findings of cohort studies.There were a number of reasons why N-glycome of bloodplasma became the main research focus: first, comparedto other human tissues, blood plasma is a more accessiblesubject matter; second, as said above, the technologies forN-glycan level measurement and structure identificationwere more refined. The most common glycoproteins studiedin human blood plasma were immunoglobulins G, A, and M,fibrinogen, transferrin, haptoglobin, etc. ,while liver cells and antibody-producing cells were the mainglycoprotein source .Population variability of human blood plasma glycans,their heritability (trait dispersion due to genetic differences),as well as the effects of various environmental factors onglycan levels were studied in . Glycanlevels were measured using HPLC. The authors of the papermade several major conclusions. First, high population variabilityof glycosylation levels was discovered. Second, theauthors discovered the significant effect biological sex andage had on glycan levels. Third, heritability of glycan levelsvaried (the average heritability index h2 = 34.7 % and thestandard deviation of 15.5 %), which implies that glycanswere controlled by both genetic and environmental factors.In , the authors assessed the heritabilityof 39 N-glycan traits measured using UHPLC. It wasshown that the heritability was over 50 % (average heritabilityindex h2 = 48.0 % and the standard deviation of 17.7 %)for 24 out of 39 traits, which confirmed the hypothesis onthe significant effect both environmental and genetic factorshad on blood plasma glycome. In , the authors pointed out the highest heritability(> 50 %) in biantennary glycans with backbone fucosylationand reduced sialylation of antennary chains included inimmunoglobulins, primarily IgG being the most commonglycoprotein among all human blood plasma proteins.Average and high heritability (30\u201362 %) was observed inbi- and triantennary glycans with high sialylation of antennarychains. In , the authors assumed thathigh heritability in this case might be explained by the presence of these structures in a large number of glycoproteins causing errors in estimating genetic factors foreach of them in isolation, and by the fact that these glycanswere primarily contained in glycoproteins synthesized byliver cells, specifically acute-phase proteins, the glycosylationof which was significantly affected by the environmentDespite the fact that heritability studies have made it possibleto estimate the portion of trait variability controlled bygenome, they have not revealed specific genomic regionsaffecting the manifestation of traits. The latter may be foundusing quantitative trait gene mapping methods, in particulargenome-wide association studiesGenome-wide association study (GWAS) is the most commonmethod for mapping loci of human diseases and complextraits. This method implies the analysis of associationsbetween a large number (hundreds of thousands to tens ofmillions) of genetic markers distributed across the whole genomeand the studied trait. Typically, large samples of species or individuals are analyzed.The availability of these data makes it possible to essentiallytest the whole genome for associations with the studied traitand find new previously undiscovered associations betweenloci and traits. GWAS studies are usually designed aroundseveral samples. The findings from samples are combinedusing genome-wide meta-analysis techniques , which increases the total sample size and thestatistical power of the association analysisThe presence of the association between a genomic locusand the studied trait does not by itself clarify the molecularbiological mechanism underlying the discovered association.The discovered loci may contain from one to tens of genes,but they can also include none . There is a multitude of reasons why an association canoccur, i. e. the presence of encoding substitutions in the locusaffecting the structure and functioning of the gene product(protein or RNA) or the presence of substitutions affectingthe specificity of binding between transcription factors andregulatory regions. The number of functional variants mayvary from one to many .Identification of functional genes in the discovered lociand the mechanisms of their effect on the studied traits isthe critical problem of functional studies performed usingmolecular and cellular biology methods. Here, the numberof possible hypotheses to be tested grows geometrically (intheory) depending on the number of possible molecular associationmechanisms. Taking into account the complexity,expensiveness, and labor intensity of molecular and cellularbiological methods, primary bioinformatic prioritizationof hypotheses on the association mechanisms becomesextremely important. Numerous methods for in silico functionalannotation have been developed making it possible to prioritize thehypotheses on association mechanisms, thereby increasingthe efficiency of future molecular and biological research.The subject matter in the available studies of genetic controlof glycosylation using the GWAS approach was as follows:the total N-glycome of human blood plasma proteins(the subject matter of this review) , N-glycomeof immunoglobulin G, i. e. the most common N-glycoproteinin blood plasma , and N-glycome of transferrin secreted by liver.At present, the results of five GWAS studies of the totalN-glycome of human blood plasma proteins are available.The first GWAS studies into N-glycosylation levels of humanproteins were performed in 2010\u20132011 . The authors used HPLC toanalyze glycosylation levels, and the marker density of thegenetic data was relatively low by today\u2019s standards at upto 2.5 million SNPs per genome. Six loci associatedwith N-glycosylation of human blood plasma proteins wereidentified in these GWAS studies. It should be noted thatnone of the studies used independent samples to confirmthe results.The study published in 2019 usedthe data from the TwinsUK Registry . The genome-wide genotypingdata and the primary UHPLC data on the N-glycomeof blood plasma proteins were available for 2763 participants.The SNP number was increased from 2.5 to 8.5 millionby means of imputation using the data of the 1000 GenomesProject and the appropriate quality control. As aresult, the association was confirmed for 5 out of 6 previouslyidentified loci (except for SLC9A9), and 10 new loci werediscovered.Based on four studies , associations with 16 lociwere found, with 15 of them confirmed later in (see the Table) using the largest (at the timeof the study) collection of genomic and glycomic data for4802 specimens from four samples, namely EPIC-Potsdam,PainOmics, SOCCS, and SABRE, described in detail inthe appendices . To put it briefly,the participants of the aforementioned studies were genotypedusing the following DNA chips: EPIC-Potsdam , PainOmics, SOCCS , SABRE .EPIC-Potsdam cohort study included 27,000 participantsat the ages from 35 to 65, who were selected randomly fromthe population of the city of Potsdam (Germany) in the yearsfrom 1994 to 1998 . PainOmics was the case-control study aimed at findingpotential biomarkers for dorsalgia and therapeutic targets forits management. The sample of 3400 participants includingthe residents of Italy, Belgium, England, and Croatia wascomposed in the years from 2014 to 2016.The Scottish project SOCCS was the case-control study aimed atinvestigating the risk factors of colorectal cancer. The dataon 2000 colorectal cancer patients and 2100 control subjectswere collected in the research. SABRE is the populationstudy initiated in 1988 . Overall, the dataon 4800 participants aged from 40 to 69 residing in WestLondon (Great Britain) were collected.To prioritize new protein glycosylation regulator genesin the confirmed loci and pose hypotheses on potentialmechanisms at work in these loci, the authors of used a combination of quantitative genetics andbioinformatics methods and approaches as follows1. Gene prioritization based on the results of eQTL colocalizationanalysis. Colocalization methods, particularlythe SMR/HEIDI method used by theauthors, made it possible to identify genes, the changesin the expression of which (at the mRNA level) mediatedthe association between SNPs and the studied trait.2. Gene prioritization based on the determination of possiblefunctional consequences of nucleotide substitutionswith high SNP linkage disequilibrium associatedwith N-glycome traits. The VEP ,FATHMM-XF , and FATHMM-InDel methods were used to select SNPs,where substitutions changed the primary amino acid sequenceof a protein and/or were recognized as pathogenic.Genes with sequences affected by said substitutions wereprioritized as candidate genes.3. Gene prioritization based on their involvement in variousbiological pathways. The DEPICT method prioritized genes and biological pathways basedon the results of enrichment analysis , which in turn was performedbased on the pre-calculated probability of involvementof a specific locus in a particular gene network and/orbiological pathway.If the methods above failed to achieve gene prioritizationfor a certain locus, then the gene closest to the SNP withthe most significant association in the locus was selected.As a result of in silico studies within the investigation of thetotal N-glycome of blood plasma ,20 candidate genes were prioritized for 15 loci .The detailed description of these genes and the hypotheseson their possible roles in N-glycosylation regulation ofhuman blood plasma proteins are presented in this section.The genes coding for glycosyltransferase enzymes involvedin N-glycan biosynthesis emerge as candidate genesin 8 loci out of 15.MGAT5 coding for GnT-V enzyme, i. e. alpha-1,6-mannosylglycoprotein6-beta-N-acetylglucosaminyltransferase, isthe candidate gene in the locus on the second chromosome,125 Mbp. This enzyme transports the N-acetylglucosamineresidue to the mannose of N-glycan, which produces a tri- ortetraantennary N-glycan. The locus with MGAT5 showed anassociation with glycomic traits reflecting tri- and tetraantennaryglycan levels .MGAT3 coding for N-acetylglucosaminyltransferaseGnT-III, i. e. beta-1,4-mannosylglycoprotein 4-beta-N- acetylglucosaminyltransferase,is the candidate gene in the locuson the 22nd chromosome, 39 Mbp. This enzyme transportsthe N-acetyl glucosamine residue to the mannose of N-gly-canso as to produce backbone bisection. The pleiotropiceffect of this locus on both N-glycan levels and MGAT3 expressionin CD19+ cells (B-lymphocytes) was demonstrated.FUT8 coding for Fuc-TVIII enzyme, i. e. alpha--fucosyltransferase,is the candidate gene in the locus on the14th chromosome, 66 Mbp. This enzyme transports fucoseresidue to N-acetylglucosamine of the N-glycan backbone,and through that is responsible for N-glycan backbone fucosylation.It is worth noting that loci FUT8 and MGAT3showed association with traits FBS2/(FS2+FBS2) and FBS2/FS2 reflecting the presence of backbone bisection in biantennaryglycans with backbone fucosylation , which is consistent with the known phenomenonof interference of Fuc-TVIII and GnT-III enzyme activities.FUT6, FUT5, FUT3, and NRTN are candidate genes in thelocus on the 19th chromosome, 5.8 Mbp. NRTN codes for aneurotrophic factor regulating neuron survival and functioning.FUT6 and FUT3/FUT5 code for Fuc-TVI and Fuc-TIIIenzymes, i. e. fucosyltransferase 6 and 3, respectively, transportingfucose residue from the GDP-fucose to the N-acetylglucosamineby forming an alpha-1,3(4)-glycosydic bond.These enzymes are responsible for antennary fucosylation ofN-glycans. In , it was shown that thislocus is associated with antennary fucosylation in tri- andtetraantennary glycans. It is of note that rs17855739 SNPis located in FUT6. This SNP codes for G>A substitution, which leads to thereplacement of negatively charged glutamic acid with positivelycharged lysine at position 247 (p.Glu247Lys). Thissubstitution is located in the catalytic domain of Fuc- TVIenzyme and causes enzyme inactivation, and thereforethis variant may have functional effect on glycosylation ofhuman blood plasma proteins. It should be mentioned thatFUT3, FUT5, and FUT6 descend from a common ancestralgene as a result of two duplications . Inaddition, FUT5 expression at the transcription and translationlevel in a human organism is much weaker comparedto FUT3 and FUT6 .ST6GAL1 is the candidate gene in the locus on the thirdchromosome, 186 Mbp. ST6GAL1 codes for alpha-2,6-sialyltransferase1. This enzyme catalyzes the formation of thealpha-2,6-glycosydic bond between N-acetylneuraminic acidand N-acetylglucosamine bound to galactose of N-glycan.The ST6GAL1 locus showed the association with the levelsof mono- and disialylated N-glycans and their precursors.ST3GAL4 is the candidate gene in the locus on the 11thchromosome, 126 Mbp. ST3GAL4 codes for alpha-2,3-sialyltransferaseenzyme transporting the N-acetylneuraminicacid residue. This locus showed an association with the levelsof various sialylated N-glycans .B4GALT1 is the candidate gene in the locus on the 9thchromosome, 33 Mbp. B4GALT1 codes for galactosyltransferaseenzyme binding galactose to various substrates,includingN-acetyl glucosamine. The B4GALT1 locus wasassociated with the levels of galactosylated biantennaryN-glycans and their precursors . Itis also known that a series of mutations in B4GATL1 leadsto a congenital disorder of glycosylation .B3GAT1 coding for galactosylgalactosylxylosylprotein-3-beta-glucuronosyltransferase 1 enzyme is the candidategene in the locus on the 11th chromosome, 134 Mbp. Thisenzyme catalyzes the transport of glucuronic acid in HNK-1epitope biosynthesis. This epitope is expressed on lymphocytes,but its presence on blood plasma proteins remainedundiscovered for some time. The association of this locuswith N-glycan levels in blood plasma proteins was firstshown in . The presence of glucuronicacid in N-glycome of blood plasma, which can explain theassociation of the locus, was discovered in .Candidate genes in seven other loci are not glycosyltransferasegenes. Three genes, SMARCB1, DERL3, andCHCHD10, were prioritized in the locus on the 22nd chromosome,39 Mbp. The strongest association signal in thelocus is observed in the coding sequence of SMARCB1 gene.SMARCB1 codes for the protein of hSWI/SNF complex actingas a chromatin remodeler. SMARCB1 gene product playsa major part in carcinogenesis inhibition, cell proliferationand differentiation .DERL3 codes for the enzyme involved in the degradationof luminal glycoproteins with incorrect tertiary structure inthe endoplasmic reticulum . The pathogenicvariant rs3177243 is also found in this locus, in the codingsequence of DERL3 geneCHCHD10 codes for mitochondrial protein observed infibrils of mitochondrial cristae. It was shown that geneticassociation of this locus with N-glycan levels in proteinsmay be mediated by the effect of nucleotide substitutions onCHCHD10 expression in blood cells .The direct involvement of mitochondrial proteins in glycosylationprocesses remained undiscovered before 2017,when the paper showing the role of mitochondrial fragmentationand the number of ER-mitochondria contacts in representationof sialylated glycans on the surface of glioblastomacells, which in turn affected glioblastoma cell recognitionby lymphocytes, was published .The locus on the 14th chromosome, 105 Mbp, containsthe IGH gene cluster coding for heavy chains of immunoglobulins.IgG is the most common N-glycoprotein in humanblood plasma , and its constitutiveN-glycosylation site is located in the heavy chainSLC9A9 is the candidate gene in the locus on the thirdchromosome, 142 Mbp. SLC9A9 codes for the Na+/H pump,presumably regulating the pH level in the Golgi apparatus(GA). Protein glycosylation occurs in the GA, and, accordingto the available data, it is a pH-sensitive process . The processes in the GA affect the synthesisof heterodimeric complexes responsible for glycosylation. It was shown in that a pH increase in the GA may disrupt terminalN-glycosylation due to incorrectlocalization of glycosyltransferases. In accordance with thishypothesis, the SLC9A9 locus showed an association withtetra-sialylated N-glycan levels in and with sialylated N-glycan levels in .HNF1A is the candidate gene in the locus on the 12thchromosome, 121 Mbp. A detailed functional study into thislocus in showed that HNF1A coding forthe hepatocyte transcription factor regulates the expressionof most fucosyltransferase encoding genes, FUT3, FUT5,FUT6, FUT8, FUT10, and FUT11, in the HepG2 cell lineobtained from liver cells. The same study demonstrated thatHNF1A regulates the expression of genes encoding the keyGDP-fucose synthesys enzymes, and GDP-fucose acts as asubstrate for fucosyltransferases. This implies that HNF1Aplays a major part in glycan fucosylation processes.IKZF1 is the candidate gene for the locus on the 7th chromosome,50 Mbp. It was shown earlier that this locus was associated with IgG glycosylation, andIKZF1 was suggested as the candidate gene for the locus.IKZF1 encodes the DNA-binding protein Ikaros, a transcriptionregulator involved in chromatin remodeling. It isof note that the IKZF1 locus showed the association withlevels of N-glycans with backbone fucosylation in bloodplasma proteins, with which the FUT8 locus was associated. IKZF1 is considered as an importantlymphocyte differentiation regulator .Since IgG-secreting cells are lymphocyte derivatives,IKZF1 gene was selected as the candidate gene in the locus,and the hypothesis on its role in regulation of backbonefucosylation in IgG N-glycans through FUT8 expressionregulation was posed . In addition, itwas experimentally shown in that IKZF1knockdown in MATAT6 IgG-secreting cells leads to morethan tripled FUT8 expression and increased fucosylationlevel in the secreted IgG.RUNX3 is the candidate gene in the locus on the firstchromosome, 25 Mbp. This gene codes for Runt domaincontainingprotein, a transcription factor, which, similarlyto IKZF1 , plays a major part in B-lymphocytematuration and differentiation.The candidate genes for the HLA locus (human majorhistocompatibilitycomplex) on the sixth chromosome,25\u201332 Mbp, are not presented due to a high chance of falsepositive. The HLA locus is unique in terms of quantitativegeneticsof multifactorial human traits . This locus shows the highest gene density in thehuman genome; it also demonstrates the highest degree ofpolymorphismat the nucleotide level; locus alleles showhigh linkage disequilibrium throughout the whole locusspanning 8 Mbp.The recent studies into N-glycome of blood plasma have demonstrated a significantassociation of 15 loci with 116 out of 117 glycan traits. Intotal, significant association has been shown by 214 locustraitpairs. These data were used in toreconstruct the gene regulatory network of N-glycan levelsin blood plasma proteins . This network visualizesthe association between the discovered loci and N-glycanlevels in blood plasma proteins.To build the network, glycomic traits were classified intofour groups based on the tissue secreting N-glycoproteinsinto blood plasma. The first group included the traits reflectingN-glycan levels in immunoglobulins secreted by lymphocytic series cells, i. e.B-lymphocytes, plasmoblasts, and plasmocytes. The secondgroup were the traits reflecting N-glycan levels inproteins primarily secretedby hepatocytes, i. e. liver cells. The third group were the traits reflecting N-glycan levels in proteins secreted by bothB-lymphocytes and their descendants and hepatocytes. Thefourth group included the traits that were not classified. Theclassification was based on the data on glycoprotein presencepublished in , where the authors evaluatedthe contribution of each N-glycoprotein into the N-glycomeof human blood plasmaThe loci and the associated traits in the network maybe visually divided into two partially overlapping subnetworks.The first subnetwork is formed by loci containingST3GAL4, B3GAT1, MGAT5, HNF1A, FUT3/FUT6, FUT8,and SLC9A9genes. This subnetwork is associated withN- glycans linked to N-glycoproteins secreted into the bloodstream by liver cells. Most of these traits reflect levels of triortetraantennaryN-glycans absent in immunoglobulins.This networkincludes the HNF1A locus encoding a hepatocytetranscription factor. The HNF1A locus, is associatedwith the same traits as the FUT3/FUT6 locus, which agreeswith the role of HNF1A in fucosyltransferase expressionregulation proved earlier . The resultsobtained make it possible to pose a hypothesis that this genesubnetwork regulates glycosylation processes in hepatocytes.The role of candidate genes from this network is tobe tested in liver cells, e. g., hepatocytes, or cells close tothem, e. g., HepG2 cell line.The second subnetwork is formed by loci containingFUT8, FUT6/FUT3, SLC9A9, IKZF1, MGAT3, RUNX3,SMARCB1/DERL3/CHCHD10, B4GALT1, ST6GAL1, and IGH/TMEM121 genes. These loci are associated withN-glycanslinked to immunoglobulins secreted into bloodstream by lymphocytary series cells. In addition, it wasshown in GWAS studies of N-glycan levels in IgG that theseloci are associated with IgG N-glycosylation . Since IgG is the most commonglycoprotein in blood plasma, it can be hypothesized thatcandidate genes from this network regulate N-glycosylationprocesses in B-lymphocytes and their descendants. The roleof candidate genes from this network should likely be testedin antibody-producing cells and cells close to them.The role of transcription factor IKZF1 in FUT8 expressionregulation in the lymphoid line GM12878 was provedin . Furthermore, IKZF1 knockdown resultedin increased fucosylated protein level, which provesthe role of transcription factor IKZF1 in protein fucosylationregulation as a result of in vitro experiment.The GWAS approach was used to identify a total of16 loci, and associations of 15 of them were confirmed inindependent samples. An in silico study was performed for15 confirmed loci, and 20 candidate genes were suggested.As a result of in vitro experiments, the role of transcriptionfactor IKZF1 in protein fucosylation regulation andthe role of HNF1A in fucosyltransferase expression regulationwere proved. The role of transcription factor RUNX3 inN-glycosylation regulation was confirmed by targeted genomeediting (using CRISPR-dCas9 system) in cell linesVPR-dCas9 and KRAB-dCas9 HEK-293F secreting IgGinto the environment. Comparison of the IgG N-glycosylationprofile with the non-modified control cell line showedthat increased RUNX3 gene expression leads to a significantreduction of galactosylated structures with a further increasein agalactosylated structures .The results of GWAS studies of N-glycan levels in bloodplasma proteins confirm the understanding of N-glycosylationof human blood plasma proteins as a complex processcontrolled by genes involved in various biological pathwaysand expressed in various tissues. The candidate genes suggestedas a result of a large-scale in silico investigation of the confirmed loci make it possibleto pose functional hypotheses on the mechanisms underlyingthe effect of the discovered loci on N-glycosylationof blood plasma proteins. These hypotheses will be of usein the planning of in vitro and in vivo molecular geneticstudies of glycome and its role in pathogenesis of sociallyand economically important human diseases. The resultsof the performed in vitro experiments solidify the scientificcredence of functional hypotheses with regard to candidategenes suggested using the GWAS approach.There are several development trends for human populationglycogenomics. Larger-scale GWAS studies intoN-glycanlevels using larger samples will be performed.New functional genomic data applicable to studying N-glycosylationprocesses will be available, which, combined withthe GWAS results, will make it possible to identify more lociand potential N-glycosylation regulators. The application ofthe GWAS approach in glycosylation regulation studies iscurrently restricted to the analysis of the total N-glycome ofblood plasma and N-glycome of IgG and transferrin. Thedevelopment of N-glycome profiling technologies will expandthe variety of proteins, the individual N-glycosylationprofiles of which will be studied. On the other hand, highthroughputtechnologies for N-glycome profiling in otherhuman tissues are likely to emerge. The advancementslisted above will make it possible to better understandN-glycosylationregulation in human proteins and throughthat determine the role of glycosylation in pathogenesis ofglycome-associated diseases and boost the development ofnew methods for prediction, prophylaxis, diagnostics andmanagement of these diseases.The authors declare no conflict of interest.Akma\u010di\u0107 I.T., Ugrina I., \u0160tambuk J., Gudelj I., Vu\u010dkovi\u0107 F., Lauc G.,Pu\u010di\u0107-Bakovi\u0107 M. 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DOI10.1021/acs.jproteome.9b00348.Zhu Z., Zhang F., Hu H., Bakshi A., Robinson M.R., Powell J.E., MontgomeryG.W., Goddard M.E., Wray N.R., Visscher P.M., Yang J. Integrationof summary data from GWAS and eQTL studies predictscomplex trait gene targets. Nat. Genet. 2016;48(5):481-487. DOI10.1038/ng.3538."} +{"text": "Paraclostridium bifermentans (P.b) is an emerging human pathogen that is phylogenomically close to Paeniclostridium sordellii (P.s), while their populational genomic features and virulence capacity remain understudied. Here, we performed comparative genomic analyses of P.b and compared their pan-genomic features and virulence coding profiles to those of P.s. Our results revealed that P.b has a more plastic pangenome, a larger genome size, and a higher GC content than P.s. Interestingly, the P.b and P.s share similar core-genomic functions, but P.b encodes more functions in nutrient metabolism and energy conversion and fewer functions in host defense in their accessory-genomes. The P.b may initiate extracellular infection processes similar to those of P.s and Clostridium perfringens by encoding three toxin homologs in their core-genomes. However, P.b is less toxic than the P.s by encoding fewer secretion toxins in the core-genome and fewer lethal toxins in the accessory-genome. Notably, P.b carries more toxins genes in their accessory-genomes, particularly those of plasmid origin. Moreover, three within-species and highly conserved plasmid groups, encoding virulence, gene acquisition, and adaptation, were carried by 25\u201333% of P.b strains and clustered by isolation source rather than geography. This study characterized the pan-genomic virulence features of P.b for the first time, and revealed that P. bifermentans is an emerging pathogen that can threaten human health in many aspects, emphasizing the importance of phenotypic and genomic characterizations of in situ clinical isolates. It is wfections . In addifections . Up to dP. bifermentans and P. sordellii from the NCBI genome database. We analyzed the phylogenetic relationship between the two species by constructing a phylogenomic tree and performing whole-genome-sequence-based average nucleotide identity (ANI) analysis. Furthermore, we annotated and compared the pangenome and coregenome features of the two species, including general genomic characteristics such as genomic size, GC content, and coding density, as well as global gene functions and virulence factor coding profiles. Additionally, we explored the extrachromosomal toxin coding capacity of P. bifermentans for the first time by predicting, annotating, and grouping the virulence plasmid sequences based on sequence identity. The toxicity potential and pathogenesis of P. bifermentans were then proposed and discussed in detail.In this study, we obtained the whole genome sequences of Paraclostridium spp. and P. sordellii were downloaded from the NCBI genome Refseq database. The isolation sources of each strain were collected from the metadata table downloaded from the Refseq database or by searching the literature. The genomic sequences were evaluated for completeness and contamination using CheckM v1.0.12 circular contigs with no dnaA gene and no rRNA coding sequences although not predicted as plasmids based on the sequence homology methods. Pangenome features of either P. bifermentans or P. sordellii were extracted using the Roary v3.11.2 pangenome pipeline from the gff files produced by Prokka v1.14.5. Subsequently, the extracted pangenome features were analyzed and visualized using the R package Pagoo v0.3.12 (Plasmid sequences in the genome sets were predicted using (1) PlasForest v1.2, v0.3.12 . The cor v0.3.12 . Virulen v0.3.12 .P. sordellii strains in the environment, none of the strains that had genomes sequenced are isolated from the environment, while 15 originated from animal sources and 45 from human sources. In contrast, strain P. benzoelyticum JC272 was isolated from the environment, and 6, 6, and 13 out of the 26 P. bifermentans strains were isolated from environmental, animal, and human sources, respectively (P. bifermentans (P.b) and P. sordellii (P.s) did not reveal any correlation between isolation source and within-species phylogeny, indicating that isolation source did not impact the phylogenetic relationships within these species (P. benzoelyticum); (3) they were identified as outliers in both genome size and GC content .P. bifermentans is significantly divergent from P. sordellii . Moreoveb>yP.s) ,C, whichb>yP.s) . As the b>yP.s) , the comb>yP.s) \u2013D. The cb>yP.s) ,C. The cb>yP.s) . P.b\u2019s ab>yP.s) .We further explored the virulence factor coding capacity of P.b and P.s to compare their pathogenic potentials. The virulence gene profiles between P.b and P.s were divergent, enabling effective discrimination between the two species . SpecifiWe further compared the toxin gene counts derived from different sequence types to estimate the virulence coding capacity of P.b and P.s. The results showed no significant difference in the pangenome-coded toxin gene counts between P.b and P.s. However, the coregenome-coded toxin genes in P.s were higher than those in P.b \u2013C. MoreocolA, pfo, plc, toxB/tcsL, and iap, were shared by both species. The former three genes were core genes in both species that coded for proteins involved in host cell surface attachment and cell membrane damage, indicating that P.b and P.s may share similar mechanisms for initiating infections are core genes in P.b , 5,6-dimethylbenzimidazole synthesis (nox_2), styrene degradation (gatA), aminoacyl-tRNA biosynthesis , etc. and one novel neurotoxin, which are flanked by Tn3 and IS1182 family transposases, respectively , etc. . Additioectively . Notablyectively ,C. Whileynthesis , surfaceynthesis , and salynthesis . Conversynthesis . Interesynthesis , which mynthesis . Furtherynthesis .As a species that is phylogenomically close to the pathogen P.s in clostridial XI, P.b is being recognized as an emerging human pathogen. Despite this, the strain-level diversity, toxicity, and genomic virulence capacity of P.b strains are yet understudied. This study reveals that P.b possesses a larger genome size with a higher GC content than P.s. Additionally, both P.b and P.s possess an open pangenome, with that of P.b being more plastic. While the gene function profiles of P.b and P.s are similar in the core-genomes, they differ significantly in the accessory genomes. P.s is more toxic than P.b, as it carries more toxin genes and encodes more secretion toxins in the core-genome and carries lethal toxin genes in the accessory genome. However, plasmid-originated toxin genes are more abundant in the pangenome or core-genome of P.b. Notably, plasmids were discovered to be species-conserved among P.b., P.s., and C.p. Furthermore, these plasmids were discovered to be clustered not by geographic location but by isolation source in P.b. This study also identified conserved Tn3 and IS1182 family transposase coding genes flanked by toxin coding genes in P.b, which may facilitate the acquisition and spread of virulence genes for P.b strains.Previous studies have revealed that a larger genome and higher GC content elicit bacteria adaptation in more complex and varied environments . In the C. difficile and P. s, and phylogenomically closer to the latter (iap), encoding actin cytoskeleton destroying functions, is present in 12.5% of the P.b strains compared to 100% present in P.s strains , phagosomal escaping (L. monocytogenes), and macrophage escaping (C.p) , which hand plc) . Studiesand plc) . Neverth strains . Additio strains . Further strains . Previou strains . Moreovetococcus , contribng (C.p) . HoweversrtB)). Other plasmid families, such as pCS2, have also been identified in P.s, but they are poorly characterized . The mobile nature of these virulence genes facilitates their wide dissemination within the clostridial genera . The letcterized . Our stucterized , and eigcterized . Interesumstance . Unlike umstance . For inst efflux ; tlyC col escape ; asrABC-l cancer . Of notel cancer . A simill cancer . Moreovel cancer . Up to dP. bifermentans carries a highly plastic pangenome as an emerging human pathogen. The core-genome of this species encodes at least three clostridial toxin homologs that are associated with extracellular matrix degradation and cell membrane damage, which can initiate extracellular infections. MGEs, particularly plasmids, have greatly contributed to the broadening of virulence, adaptation, and metabolism gene pools of this species. Although no lethally toxic strains in this species have been reported, the high prevalence of plasmids and transposons in the genomes highlights the potential risk for the emergence of lethal strains. Of note, this species may trigger colorectal cancer by producing genotoxic hydrogen sulfide in the gut tract. Inherent limitations arise in this study due to the absence of validation for specific clinically-related results through wet-bench experiments, and the scarcity of clinically-derived P. bifermentans genomes in public databases hampers extensive large-scale analyses. Nevertheless, this study significantly contributes to our understanding of the population genomics insights on phylogeny and pathogenesis associated with the emerging human pathogen P. bifermentans. The findings underscore the imperative for enhanced efforts in the isolation and sequencing of clinically-relevant P. bifermentans strains. Such endeavors are crucial to proactively mitigate the potential threats posed by these strains to human health.In conclusion, this study revealed that The original contributions presented in the study are included in the article/XC: Data curation, Funding acquisition, Writing \u2013 original draft. YP: Data curation, Writing \u2013 original draft. GY: Investigation, Methodology, Writing \u2013 review & editing. LF: Resources, Writing \u2013 review & editing. XT: Validation, Writing \u2013 review & editing. PH: Investigation, Writing \u2013 review & editing. YM: Conceptualization, Funding acquisition, Supervision, Writing \u2013 review & editing. LX: Conceptualization, Funding acquisition, Supervision, Writing \u2013 review & editing."} +{"text": "Nature Communications 10.1038/s41467-023-37385-0, published online 18 April 2023Correction to: https://www.nespmarinecoastal.edu.au/project-1-9-final-report-2/\u2019and \u2018Zimmerhackel et al. 2023 - Zimmerhackel, J. S., Pineiro-Corbeira, C., Norderhaug, K. M., Filbee-Dexter, K., & Wernberg, T. (2023) Dependency of commercial fisheries on kelp forests for valuation of ecosystem services. Working Paper 2302, Agricultural and Resource Economics, The University of Western Australia, Crawley, Australia. 10.22004/ag.econ.334183\u2019.The original version of this article omitted a reference to previous work in \u2018Eger et al. 2022 - Eger, A. M, Bennett, S., Zimmerhackel, J., Rogers, A., Burton, M., Filbee-Dexter, K., Wernberg, T., Gacutan, J., Milligan, B., Verg\u00e9s, A. (2022) Quantifying the ecosystem services of the Great Southern Reef. Report to the National Environmental Science Program. University of New South Wales. Available at: 110,111\u2019. These references have been added to the reference list.These have been added as references 110, 111 at: \u2018We accounted for this fact by creating dependency classes for 187 genera of fish and invertebrates, adapted from refs. The original version of this article contained an error in the \u201cAcknowledgements\u201d, which incorrectly omitted the following: \u2018A.E., A.V., D.S., and P.M. would also like to acknowledge our continued collaboration with the GEAK network and our valued discussions on how to value ecosystem services in kelp forests. In particular, we thank Johanna Zimmerhackel, Cristina Pineiro-Corbeira, Kjell-Magnus Norderhaug, Karen Filbee-Dexter, and Thomas Wernberg for their thinking and work on fisheries dependencies in kelp forest ecosystems.\u2019This has been corrected in both the PDF and HTML versions of the article."} +{"text": "Psocoptera from 15 families and three suborders from Georgia, of which 31 species are recorded for the first time, increasing the known fauna of the country by more than 65%. Of these, 37 species have been barcoded, representing 210 Barcode Identification Numbers (BINs). An additional 14 species are expected to occur in Georgia but remain undiscovered, meaning that only \u2248 77% of the fauna is currently documented. Barcodes, comments on distributions, and images of voucher specimens are given followed by a map of the sampling sites.This checklist reports 47 species of Psocoptera, known as the booklice and barklice, is an order of hemimetabolous insects having approximately 6000 described species worldwide (Trogiomorpha (booklice), Troctomorpha (booklice), and Psocomorpha (barklice). While most of them (mainly species belonging to the suborder Psocomorpha) are bark- or leaf-dwellers found outdoors, there are domiciliary species exhibiting excellent powers of dispersal and readily spread by humans all over the world. For some species, this makes it difficult to reconstruct the original distribution or to distinguish between native and introduced once have evolved within the Troctomorpha suborder and, based on both morphological and molecular data, are probably sister group to Liposcelididae, or, various lines of Phthiraptera may have budded off independently in the infraorder Nanopsocetae within Troctomorpha.Although Psocoptera and Phthiraptera are now placed in the order Psocodea project, being the most ambitious arthropod inventories ever performed in Georgia by the members of the GGBC (Georgian-German Biodiversity Center) and the CaBOL team of the Institute of Ecology, Ilia State University (https://ggbc.eu/). Most of the samples were collected using 18 Malaise traps installed in various habitats of the Kintrishi National Park from 20 April to 3 November 2018 at altitudes ranging from 403 m up to 2465 m were amplified by polymerase chain reaction (PCR) using the primer pair LCOI490-JJ and HCO2198-JJ by using the amplification primers. Sequence analysis was performed using Geneious Prime 2022.1.1 (http://www.geneious.com). Extracted DNA was deposited in the scientific collections of Ilia State University, Tbilisi, Georgia and aliquots will be deposited at LIB Biobank at Museum Koenig, Bonn, Germany, while the sequences have been submitted to Barcode of Life Data System (BOLD) databases. The newly obtained DNA barcodes of COI sequences were checked out against the BOLD systems database (http://www.boldsystems.org/index.php). Barcode Index Number (BIN) (BOLD systems (if they had a BIN) are also given. For the calculation of sequence differentiation, we used p distance as performed in the BOLD system.DNA was extracted from whole samples using the Quick-DNA Magbead Plus Kit (Zymo Research). Partial sequences of cytochrome oxidase subunit I for the In total 2353 specimens were collected representing 45 species comprising 15 families , 1027571, 1027572, 1012880, 1012881, 1012882, 1012883, 1012884 and 1012885 (BOLD:AFC5936) (maximum p-distance 1.52%) with the nearest neighbor in BOLD systems being K.quisquiliarum from Finland . Examined specimens perfectly matched the description provided by COI distance (over 5%) between the populations of K.quisquiliarum might indicate the existence of a cryptic species complex in western Palaearctic, and further study is needed to solve this puzzle.Remarks. The species is characterized by micropterous females.Caeciliusidae Kolbe, 1880Family Note. Five species are recorded from Georgia.C.fuscopterus * Fig. 3BMaterial examined. 74 \u2640\u2640, 60 \u2642\u2642.Distribution in Georgia. Kintrishi National Park, Lagodekhi National Park, Shilda.Distribution in Caucasus. Karachay-Cherkessia originating from two populations, with the nearest neighbor in BOLD systems being C.fuscopterus from Finland . Examined specimens perfectly matched the description provided by COI distance (over 5%) between the populations of C.fuscopterus might indicate the existence of a cryptic species complex in western Palaearctic, and further study is needed to solve this puzzle.V.atricornis * Material examined. 42 \u2640\u2640, 64 \u2642\u2642.Distribution in Georgia. Churia, Kintrishi National Park, Meore Moidanakhe, Shilda.Distribution in Caucasus. Georgia.Global distribution. Holarctic that were identical to V.atricornis from Finland (BOLD:ACG3154).Remarks. Originally V.atricornis is a species with Palaearctic distribution, introduced to North America from Hungary Material examined. 20 \u2640\u2640, 9 \u2642\u2642.Distribution in Georgia. Sokhumi Botanical Garden with the nearest neighbor in BOLD systems being V.burmeisteri from Germany .V.flavidus Material examined. 152 \u2640\u2640.Distribution in Georgia. Batumi Botanical Garden .erkessia , Armeniaerkessia , GeorgiaGlobal distribution. Holarctic , with the nearest neighbor in BOLD systems being V.flavidus from Canada .Remarks. The species is known to have asexual parthenogenetic populations in Europe, consisting of triploid females, but is believed to have sexual and asexual populations in North America as well (de Moya 2022).V.piceus Material examined. 1 \u2640.Distribution in Georgia. Batumi Botanical Garden .erkessia , GeorgiaGlobal distribution. European part of Western Palaearctic * Material examined. 258 \u2640\u2640, 168 \u2642\u2642.Distribution in Georgia. Chkhorotsku, Dedoplistskaro, Kintrishi National Park, Mandaeti, Shilda, Tbilisi.Distribution in Caucasus. North Caucasus: Krasnodar Krai with the nearest neighbor in BOLD systems being E.cryptomeriae from Canada .Remarks.Ectopsocopsiscryptomeriae is a species of an Asian origin identical to COI of E.briggsi from United States and Canada (BOLD:AAN8452) in BOLD systems.E.meridionalis Ribaga, 1904* Material examined. 11 \u2640\u2640.Distribution in Georgia. Patara Dmanisi, Tbilisi.Global distribution. Subcosmopolitan - has not been recorded from Australia , 1032232, 1032233, 1032234, 1032235 (BOLD:AAM8931) (mean p-distance 2.53%) identical to COI of E.meridionalis from Costa Rica, Germany (BOLD:ADB3092) and Canada (BOLD:AAM8931) in BOLD systems.Remarks. Cryptogenic species of unknown origin , 1 \u2640 (brachypterous).Distribution in Georgia. Dighomi village, Tbilisi.Distribution in Caucasus. Armenia . There are no barcodes of the species available in BOLD systems as we submit the first ones.Remark. This is by far the northernmost record of the species after it was reported from Armenia as E.brunneus Vishnyakova, 1963 * Material examined. 17 \u2640\u2640.Distribution in Georgia. Kintrishi National Park, Mukhura, Tbilisi.Distribution in Caucasus. Georgia.Global distribution. Palaearctic (aearctic .Genetics. We obtained a single barcode from the specimen with CaBOL-ID 1032265 (BOLD:AFD9323). There are no barcodes of the species available in BOLD systems as we submit the first one.E.moebiusi Tetens, 1891* Material examined. 12 \u2640\u2640, 12 \u2642\u2642.Distribution in Georgia. Kintrishi National Park.Distribution in Caucasus. Karachay-Cherkessia with the nearest neighbor in BOLD systems being E.moebiusi from Canada .H.hispanica * Material examined. 1 \u2640.Distribution in Georgia. Pia (Samtskhe-Javakheti).Distribution in Caucasus. Armenia . There are no barcodes of the species available in BOLD systems as we submit the first one.Epipsocidae Karny, 1930Family *Note. The representatives of the family have not previously been known to occur in Georgia. One species has been recorded within the current study.B.lucifuga * Material examined. 2 \u2640\u2640.Distribution in Georgia. Tekhuri River gorge (Martvili).Distribution in Caucasus. Georgia.Global distribution. Western Palaearctic .L.pedicularia * Fig. 3DMaterial examined. 30 \u2640\u2640, 32 \u2642\u2642.Distribution in Georgia. Kintrishi National Park, Mandaeti, Mukhura, Shilda, Tbilisi.Distribution in Caucasus. Armenia with the nearest neighbor in BOLD systems being L.pedicularia from Canada .L.quercus Fig. 3BMaterial examined. 26 \u2640\u2640, 64 \u2642\u2642.Distribution in Georgia.Distribution in Caucasus. Armenia with the nearest neighbor in BOLD systems being L.quercus from Finland .Mesopsocidae Enderlein, 1901Family Note. Two species are recorded from Georgia.M.laticeps * Material examined. 1 \u2642.Distribution in Georgia. Gori.Distribution in Caucasus. Georgia.Global distribution. Holarctic Fig. 4AMaterial examined. 5 \u2640\u2640, 7 \u2642\u2642.Distribution in Georgia. Batumi Botanical Garden , with the nearest neighbor in BOLD systems P.alboguttatus from Bulgaria .P.didymus Roesler, 1939* Material examined. 2 \u2640\u2640, 5 \u2642\u2642.Distribution in Georgia. Churia, Kintrishi National Park.Distribution in Caucasus. Georgia.Global distribution. Palaearctic are the first ones of the species that we submit in BOLD systems.Remarks. Described from southern Russia (Krasnodar Krai) this is the first time the species is reported from South Caucasus, extending its known range south by 190 km.P.phaeopterus Material examined. 3 \u2640\u2640, 2 \u2642\u2642.Distribution in Georgia. Batumi Botanical Garden Material examined. 62 \u2640\u2640.Distribution in Georgia. Sokhumi Botanical Garden , all identical to each other and to COI of P.subfasciatus from Germany (BOLD:AAN8450).Philotarsidae Pearman, 1936Family Note. Two species are recorded from Georgia.A.badonneli Fig. 4BMaterial examined. 22 \u2640\u2640.Distribution in Georgia. Sokhumi Botanical Garden , North Caucasus: Krasnodar Krai with the nearest neighbor in BOLD systems being Aaroniella sp. from United States .Remarks.Aaroniellabadonneli is the only psocid species originally described from Georgia Material examined. 1 \u2640.Distribution in Georgia. Sokhumi Botanical Garden identical to the COI of the P.picicornis from Canada (BOLD:ACB7137) in BOLD systems.Psocidae Roesler, 1940Family Note. Nine species are recorded from Georgia.A.contaminata Material examined. 16 \u2640\u2640, 19 \u2642\u2642.Distribution in Georgia. Sokhumi Botanical Garden with the nearest neighbor in BOLD systems being A.contaminata from Germany with a private status (mean p-distance 1.14%).L.fasciata * Material examined. 1\u2640, 1\u2642, 2 nymphsDistribution in Georgia. Kintrishi National Park.Distribution in Caucasus. Georgia.Global distribution. Holarctic with the nearest neighbor in BOLD systems being L.fasciata from Norway .L.variegata * Material examined. 2 nymphsDistribution in Georgia. Lebarde.Distribution in Caucasus. Karachay-Cherkessia with the nearest neighbor in BOLD systems being L.variegata from Finland .N.rhenanus Kolbe, 1882* Material examined. 3 \u2640\u2640 (brachypterous), 3 \u2642\u2642.Distribution in Georgia. Gori, Vardzia.Distribution in Caucasus. Georgia.Global distribution. European part of Western Palaearctic are the first ones of the species submitted in BOLD systems.Remarks. The species is characterized by brachypterous (short-winged) females and winged males.M.nebulosus * Material examined. 10 \u2640\u2640, 3 \u2642\u2642.Distribution in Georgia. Chkhorotsku, Churia, Kintrishi National Park.Distribution in Caucasus. North Caucasus: Karachay-Cherkessia with the nearest neighbor in BOLD systems being Metylophorus sp. from Russia .P.gibbosa * Material examined. 10 \u2640\u2640, 18 \u2642\u2642.Distribution in Georgia. Kintrishi National Park.Distribution in Caucasus. North Caucasus: Karachay-Cherkessia . The newly obtained barcodes were nearly identical (maximum p-distance 0.15%) with the nearest neighbor in BOLD systems being P.gibbosa from Finland .P.bipunctatus * Material examined. 3 \u2642\u2642.Distribution in Georgia. Kintrishi National Park, Mukhura.Distribution in Caucasus. Georgia.Global distribution. Palaearctic with the nearest neighbor in BOLD systems being P.bipunctatus from Finland .T.alexanderae Sommerman, 1948* Material examined. 6 \u2640\u2640, 2 \u2642\u2642.Distribution in Georgia. Kintrishi National Park, Torsa.Distribution in Caucasus. Georgia.Global distribution. Nearctic . The newly obtained barcodes were identical to each other as well as the nearest neighbor in BOLD systems T.alexanderae complex from Canada (BOLD:ACE6318).Remarks. The only species from T.alexanderae complex known to occur in the Western Palaearctic is T.innuptum Betz, 1983 * Fig. 4CMaterial examined. 5 \u2640\u2640, 4 \u2642\u2642.Distribution in Georgia. Telovani.Distribution in Caucasus. North Caucasus: Karachay-Cherkessia with the nearest neighbor in BOLD systems T.sexpunctatum from Finland with a private status (p-distance 1.53%).Stenopsocidae Kolbe, 1880Family Note. Three species are recorded from Georgia.E.obsoleta * Material examined. 2 \u2640\u2640, 8 \u2642\u2642.Distribution in Georgia. Kintrishi National Park.Distribution in Caucasus. Georgia.Global distribution. European part of Western Palaearctic were identical to COI of E.obsoleta from Germany (BOLD:ACC7281).G.cruciatus Fig. 4DMaterial examined. 42 \u2640\u2640, 212 \u2642\u2642.Distribution in Georgia. Batumi Botanical Garden . The nearest neighbors in BOLD systems are as follows: 1012644, 1012645 (BOLD:ACA2933) to COI of G.cruciatus from Georgia ; 1012646 (BOLD:ACA2933) to COI of G.cruciatus from Canada ; 1012647 (BOLD:ACA2933) to COI of G.cruciatus from Belarus ; 1012899, 1026995, 1030869, 1030880 (BOLD:ACA2933) to COI of G.cruciatus from Norway .S.immaculatus Material examined. 87 \u2640\u2640, 60 \u2642\u2642.Distribution in Georgia. Batumi Botanical Garden with the nearest neighbor in BOLD systems being S.immaculatus from Finland .Trichopsocidae Pearman, 1936Family Note. One species is recorded from Georgia.T.dalii Material examined. 38 \u2640\u2640, 74 \u2642\u2642.Distribution in Georgia. Sokhumi Botanical Garden , North Caucasus: Krasnodar KraaGlobal distribution. Holarctic with the nearest neighbor in BOLD systems being T.dalii from Canada .Troctomorpha Roesler, 1940Suborder Liposcelididae Enderlein, 1911Family Note. Four species are recorded from Georgia.E.enderleini * Material examined. 1 \u2640.Distribution in Georgia. Shilda.Distribution in Caucasus. Georgia.Global distribution. Argentina; Austria; Bahrein; Belgium; France; Great Britain; Italy; Madeira; South Africa , E.enderleini belongs to the genus, which is most diversified in the South American-African region .Distribution in Caucasus. Georgia.Global distribution. Cosmopolitan.Genetics. We obtained three virtually identical barcodes from the specimens with CaBOL-IDs 1027271, 1027272 and 1027275 (BOLD:ACW0584). The newly obtained barcodes were identical to the nearest neighbor in BOLD systems L.rufa from unknown place of origin (BOLD:ACW0584) mined from GenBank.Remarks. This is a species with originally a Mediterranean native range * Material examined. 28 specimens.Distribution in Georgia. Pia, Tbilisi, Vardzia.Distribution in Caucasus. Armenia , 1030815 (BOLD:AFB9104) (maximum p-distance 0.76%). There are no barcodes of the species available in BOLD systems as we submit the first ones.Remarks. Species with bisexual reproduction mainly occurring in the Mediterranean region, living in the litter, under the bark of trees, sometimes under stones * Material examined. 1 \u2640.Distribution in Georgia. Batsara Strict Nature Reserve.Distribution in Caucasus. Georgia.Global distribution. Western Palaearctic; Zimbabwe (Zimbabwe .Genetics. A single barcode obtained from the specimen with CaBOL-ID 1027292 (BOLD:ACV6564) was identical to the nearest neighbor in BOLD systems D.domestica from Canada, France, and United States (BOLD:ACV6564).Remarks.Dorypteryxdomestica originates from Africa * Material examined. 4 \u2640\u2640.Distribution in Georgia. Grigoleti, Qvabiskhevi.Distribution in Caucasus. Georgia.Global distribution. Cosmopolitan * Material examined. 25 \u2640\u2640.Distribution in Georgia. Dighomi village, Gori, Pia, Tbilisi, Vardzia.Distribution in Caucasus. Armenia with the nearest neighbor in BOLD systems being L.reticulatus from Canada .Remarks. Cryptogenic species of unknown origin males have been reported and one suborder (Trogiomorpha) that have never been previously reported from the country. Of 31 species reported for the first time from Georgia, 24 have been known to occur in the adjacent countries, 37 from the European part of the post-Soviet space and six have never been reported from the territories mentioned above (Table Danka laid a profound basis with her research on the ve Table and otheThis study, originally conceived as a small addition to the fauna of Georgian psocopterans, eventually turned into a large-scale exciting journey through the study of a new group of arthropods for the corresponding author. In the end, we hope that our study inspires the readership to spend more time in nature observing and unveiling the hidden gems, reminding them that science begins with subsiding the mind\u2019s curiosity."} +{"text": "Rep. 7, 16878 (2017). 10.1038/s41598-017-17204-5.In this article, the QuPath software was not properly cited and should have included the following citation: Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. https://qupath.github.io/97.The Code Availability sentence should have read, 'The QuPath software used for bioimage analysis is available at The original article has been corrected."} +{"text": "Candida auris is a multidrug-resistant pathogen with improved transmission dynamicsand resistance traits. During the worldwide spread of COVID-19, cases or outbreaks of C. auris colonization or infection have been reported.Resistance to antifungal drugs has been observed in the causative agents of the majority of such cases. The focus in this review is on COVID-19-associated C. auris infections(case studies/outbreaks) and the pandemic's potential effect on antifungal drug resistance.Since its first emergence in December 2019, due to its fast distribution throughout the world, SARS-COV-2 become a global concern. With the extremely increased number of hospitalized patients,this situation provided a potential basis for the transmission of nosocomial infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most significant global health event since Spanish influenza in the early 20th century, is alarmingly on the rising and threatens human health and public safety , 2. UnCandida auris, due to its persistence on hospital surfaces and high resistance to antifungal drugs, are of significant value, and COVID-19 has provided a potential bed for these infections [ The hospital mortality of COVID-19 is estimated to range from 15% to 20% and increases to 40% among patients requiring intensive care unit (ICU) admission , 7. Paections , 12. Pections , 13 . Antimicrobial resistance (AMR) as another threat to global health and the economy is likely to be overshadowed by the COVID-19 pandemic . CurrenC. auris infection/colonization among COVID-19 patients have been reported [ C. auris infection/colonization in patients with COVID-19 and the potential impact of this viral pandemic on antifungal drug resistance.So far, cases or outbreaks of eported - 18. IC. auris, first isolated in Japan in 2009, is an emerging member of the Metschnikowiaceae family within the Candida/Clavispora clade [ C. auris has been reported from at least 40 countries; therefore, it has a global distribution [ C. auris has been isolated as an infecting or colonizing agent from various specimens or parts of the human body including blood, urine, wounds, bile, the nares,the skin, the axilla, and the rectum of patients [ C. auris, leading to outbreaks [ C. auris has led to several outbreaks in hospitals worldwide and become a global health threat [ a clade . To datibution . C. auratients , 23. Fatients - 26. Ttbreaks , 28. I threat . Invasi threat .C. auris infection/colonization [ C. auris in COVID-19 patients. [ C. auris infections were extractable in 14 studies than females .The mean\u00b1SD age of patients was 63.8\u00b112.09 years [ COVID-19-associated 9 years - 45. AC. auris infections (cases/outbreaks) are not limited to a specific geographical region. As shown in COVID-19-associated C. auris is classified in five clades [ According to genetic traits, clades with di clades , 45. C clades .C. auris is reported in some studies [ C. auris isolates in different studies would be beneficial in this regard and is recommended. Inter-clade difference in susceptibility pattern of studies . ResultC. auris is more likely to cause a hospital outbreak than other Candida species [ C. auris [ C. auris outbreaks have been reported [ Due to some features, species , 50. Bspecies . Elongaspecies , 52. D. auris , 38. Beported , 53. Ieported , 38. DOne of the unforeseen and unavoidable consequences of the COVID-19 pandemic is the appearance of antimicrobial resistance . It is C. auris [ Candida species with high minimum inhibitory concentration and/or intrinsic resistance to fluconazole has been reported [ Candida species, such as C. auris [ C. auris outbreaks, drug-resistant isolates play a key role,and it makes the management more complicated. In the current pandemic, hospitalized patients with COVID-19 are more predisposed to superinfections with bacterial and/or fungal pathogens which is likely to impact the mortality rates . This p. auris . An asseported , 57. Aeported , 59, w. auris . In our. auris . As shoC. auris infections.Regarding the specific features of this fungus, it can circulate within clinical settings and cause outbreaks. Moreover, due to the different conditions in COVID-19 patientswhich are in favor of the selection of drug-resistant organisms, these patients are at risk for coinfections by single or multi-drug resistant C. auris. Accordingly,attempts for timely diagnosis and targeted treatment of such infections in COVID-19 patients should be made.With the increased hospital stay and the higher need for intensive care, COVID-19 patients are at risk for None. Conceptualization: S.K., M.A., and S.M. Literature search: J.J., S.A.H, and I.H. Draft preparation: S.K., S.A.G, and S.M. Critical review: H.T., S.A.G, M.A, and S.M. All authors read and approved the final manuscript. The authors declare no competing interests.This research received no specific grant from any funding agency, commercial or not-for-profit sectors."} +{"text": "Cranichisbeckii Kolan., Baranow, S. Nowak & A. Fuentes, sp. nov. Instead of the newly described species, the figure of Cranichisbadia was presented twice. Here, we present the correct illustration of C.beckii.In our recent work , a wrong"} +{"text": "Scientific Reports 10.1038/s41598-023-41604-5, published online 07 September 2023Correction to: Natasa Ganea was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cJ.Y. and A.J.B. developed the study concept. All authors contributed to the study design. The testing and data collection were performed by J.Y. and N.G. J.Y. performed the data analysis and interpretation under the supervision of J.B. and A.J.B. J.Y. drafted the manuscript, and N.G., S.K., M.K.Y., J.B., and A.J.B. provided critical revisions. All authors approved the final version of the manuscript for submission.\u201dThe original Article has been corrected."} +{"text": "The incidence of autistic spectrum disorders (ASD) constantly increases in the world. Studying the mechanisms underlying ASD as well as searching for new therapeutic targets are crucial tasks. Many researchers agree that autism is a neurodevelopmental disorder. Clstn2-KO mouse strain with a knockout of calsyntenin 2 gene (Clstn2) is model for investigating ASD. This study aims to evaluate the social-conditioned place preference as well as density of dopaminergic (DA) neurons in the ventral tegmental area (VTA), which belongs to the brain reward system, in the males of the Clstn2-KO strain using wild type C57BL/6J males as controls. Social-conditioned place preference test evaluates a reward-dependent component of social behavior. The results of this test revealed differences between the Clstn2-KO and the control males, as the former did not value socializing with the familiar partner, spending equal time in the isolation- and socializing-associated compartments. The Clstn2-KO group entered both compartments more frequently, but spent less time in the socializing-associated compartment compared to the controls. By contrast, the control males of the C57BL/6J strain spent more time in socializing-associated compartment and less time in the compartment that was associated with loneness. At the same time, an increased number of DA and possibly GABA neurons labeled with antibodies against the type 2 dopamine receptor as well as against tyrosine hydroxylase were detected in the VTA of the Clstn2-KO mice. Thus, a change in social-conditioned place preference in Clstn2-KO mice as well as a higher number of neurons expressing type 2 dopamine receptors and tyrosine hydroxylase in the VTA, the key structure of the mesolimbic dopaminergic pathway, were observed. Autism Spectrum Disorders (ASD) in children are characterizedby impaired social interaction, low interest in peers, anddifficulties in maintaining social contacts . Many researchers agree that the ASD aredevelopmental disorders of the nervous system .An imbalance between excitation and inhibition processes invarious brain structures is characteristic for ASD , which is caused by abnormal interactions betweenneurons and by impaired synaptic plasticity .Mutations in the adhesion proteins genes, which play a keyrole in intercellular connections, including interneuronal andneuroglial contacts, have been identified in a number of ASDstudies . In particular,impaired synthesis of neurexins, neuroligins, contactins, andcadherins may be associated with the development of ASDin humans . Also, in themouse strains modeling these disorders, the expression ofgenes responsible for the formation of these proteins may beimpaired .Calcintenin-1, -2 and -3 , belongingto the cadherin family, are synaptic adhesion proteinsthat are able to bind Ca2+ ions and regulate their intracellularconcentration. Of particular interest is Clstn2, which is specificallyexpressed in inhibitory interneurons and is associated with verbal memory in adolescents, as well as with semantic and cognitivecharacteristics in the elderly . Moreover,genetic analysis of gene copy number variation in autistic patientsrevealed a deletion of the 2nd intron of the Clstn2 gene. According to The Human Protein Atlas(https://www.proteinatlas.org/), Clstn2 in mice is expressed inthe hippocampus and some other brain structures, includingthe midbrain. To study the function of this protein, a Clstn2knockout (Clstn2-KO) mouse strain based on C57BL/6J wasestablished . As we have shown earlier, theabsence of Clstn2 in mice causes a selective deficit of inhibitoryinterneurons in the prefrontal cortex and hippocampus. This is accompanied by the manifestationof ASD-like conditions, including stereotypy, insufficientsocial motivation, abnormal ultrasonic vocalization , as well as morphologicalchanges in synapses .Previously, structural and functional disorders in the mesolimbicdopaminergic pathway, which includes the ventraltegmental area (VTA) and nucleus accumbens, were found inchildren with ASD, and these changes in the reward systemwere demonstrated to be associated with underdevelopmentof social skills . Studies demonstratethat synaptic proteins associated with the development ofASD play an important role in thefunctioning of the mesolimbic pathway of the dopaminergic(DS) and GABAergic brain systems , one of the key midbrain components ofwhich is the VTA . The VTA is a key structure of the reward brain system and regulates behavioral response toreward/ punishment,including social reinforcement . The VTA containsthe bodies of dopaminergic (DA) neurons, as well asthe glutamatergic and GABAergic neurons . Terminals of DA neurons of the dopamine mesolimbicpathway are characterized by co-transmission, i. e. the abilityto release various neurotransmitters, in particular, dopamine,glutamate, and GABA .One of the theories of autism is based on the notion thatsocial motivation is reduced in autistic persons due to thealterations in the brain reward system .Although the development of subcortical neuronal mechanismsof the brain is critical within the first months of life,the brain structures involved in the reward processes, that is,in the formation and correction of behavior through positivereactions to various stimuli, are functioning during the lifespan. The imbalance between socialand non-social motivation is the peculiar characteristic of thereward system in autistic persons . Thistheory assumes that the reward system in ASD subjects ishyperactive in response to interests unrelated to socialization,while disruption of social behavior associates underactivityof the brain reward system in response to socially significantstimuli .The neurobiological reward system includes DA neuronsof the VTA, which have projections mainly to the nucleus accumbens and to the prefrontal cortex, and regulates socialmotivation . It was demonstrated thatDA neurons of the reward system increase their activity duringthe interaction of a mouse with a relative .A characteristic feature of DA neurons is that they releasedopamine as a neurotransmitter and also contain the enzymetyrosine hydroxylase (TH), which is necessary for its synthesis. The study of Lammel et al. (2008)considers two types of DA neurons in the VTA . Type 1 DA neurons express TH and a dopamine receptortype 2 (D2R), and their terminals end up within the shell ofthe nucleus accumbens and in the dorsolateral striatum. Type 2DA neurons express TH, but not D2R, and their endings spreadto the prefrontal cortex, the core and the medial zone of theshell of the nucleus accumbens, as well as the basolateral partsof the amygdala nuclei. The D2R, which can be expressednot only on DA but also on GABAergic neurons , isassociated with addictive behavior in which the brain rewardsystem, the VTA in particular, is involved .Mice express social behavior in a variety of contexts,including interactions with peers of the same and the oppositesex, it is also involved in early play behavior and inmother-offspring interactions . The socialconditionedplace preference test evaluates social reward inyoung and adult mice when a certain context is associated withpositive social interaction with a familiar partner . Based onthis, we hypothesized that ASD-like social behavior may beassociated with impaired functioning of one or more elementsof the mesolimbic dopaminergic pathway, which plays an importantrole in the regulation of social preference .The aim of this work was to study social reward in Clstn2knockout mice (Clstn2-KO), as well as to study the densityof neurons containing D2R and TH in the VTA.Experimental animals. Seven Clstn2-KO males, and fivewild-type (C57BL/6J) males at the age of three months wereused in this study. Animals were kept in the same-sex groupsof 3\u20135 individuals in 36 \u00d7 25 \u00d7 14 cm (length \u00d7 width \u00d7 height)cages, in a conventional vivarium at the Institute of Neurosciencesand Medicine (Novosibirsk) with sawdust bedding;12D:12L cycle, at 20\u201322 \u00b0C, with free access to dry granulatedfood for laboratory rodents and to purified water. All studieswere done in accordance with the European Convention forthe Protection of Vertebrate Animals used for Experimentaland Other Scientific Purposes (ETS No. 123).Social-conditioned place preference test. The study wascarried out as described previously , with minor modifications.Briefly, on the eve of the experiment, the animals werekept individually for 24 hours. The experimental chamberconsisted of three compartments. Two outer compartments(between which there was a third \u2013 an intermediate compartment)were separated by removable partitions. The floor, madeof polypropylene, was of a different texture in the two outercompartments: rough and smooth. Before testing, the micewere adapted to the experimental cage and the selection ofthe floor texture by the tested mouse was evaluated to excludethe possibility of the preference for one or another surfacenon-related with social interaction (session \u201cadaptation\u201d).The assessment was carried out visually using a stopwatch:the time spent (in seconds) in each of the compartmentsduring 20 minutes. After adaptation, the test animals werehoused in separate cages for 24 hours. Thereafter, the mainexperiment started.The compartment with a rough surface was associated withsocial interaction, as the studied mouse was there in contactwith its familiar relative of the same sex, age, and genotype,while the compartment with a smooth surface was associatedwith isolation, as the mouse was alone there. The procedurefor establishing an \u201cassociation\u201d of the surface type with thecompartment context took three days. On the first day of theexperiment, the tested mouse was placed for 20 minutes in acompartment with a rough floor for socialization with a familiarpartner. Three hours later, the animal was transferred to acompartment with a smooth floor, where it was left alone for20 minutes. On the second day, the test mouse was first placedin the smooth surface compartment, where it was alone for20 minutes, and after three hours, it was placed in the roughsurface compartment with a partner for 20 minutes. On thethird day of the experiment, the conditions were repeatedas described for the first day. It is important to note that thefamiliar partner during the 20-minute socialization remainedthe same for each experimental animal during the three daysof social reward formation. After each 20-minute session,surfaces were cleaned up with 70 % alcohol to remove odorsand the surfaces were thoroughly dried. On the fourth day, themice explored the set for 15 minutes (basic behavior session).On the fifth day of the experiment , eachmouse was placed in the central compartment of an emptysetup, the partitions were removed to allow free movement,and the time spent in the compartments with a smooth andrough floor texture was recorded for 20 minutes. The evaluationwas carried out visually using a stopwatch. The criterionfor the presence of a mouse in a particular compartment wasthe presence of the entire body of the animal inthe compartment, either with a rough or smooth floor covering.Intracardiac perfusion. All animals used in the behavioralexperiment were perfused the day after its completionthrough the circulatory system to fix the brain. Mice wereanesthetized by intramuscular injection of 75 \u03bcL (per 10 g ofweight) medetomidine hydrochloride and 60 \u03bcL (per 10 g of weight) zoletil . Thereafter, mice were injected through the circulatorysystem with 30\u201350 mL of phosphate-buffered saline (PBS),and then 10 % formalin solution based on PBS. After that, thebrain was removed and placed in a 30 % sucrose solution inPBS at +4 \u00b0C for dehydration and further fixation for the next3\u20134 weeks until the fixed material sank to the bottom of theflask. The fixed brain samples were frozen using Tissue-TekO.C.T. and stored at \u201370 \u00b0C.Preparation of frozen brain slices. Three animals wererandomly chosen for each group for the histological analysis.Frozen brain sections from each of the animals were madeat a distance of \u20132.92 to \u20133.28 mm from the bregma, which corresponds to the area of the VTA. Sections 10 \u03bcm thickwere obtained on an HM550 OP Cryotome at \u201325 \u00b0C and placed on Superfrost Plus,Menzel-Glaser glass slides (Thermo Fisher Scientific).Immunohistochemical staining. Sample staining wasperformed according to the manufacturer\u2019s protocols withminor modifications. Briefly, after washing and exposureto Protein Block ab64226 , 50 \u03bcL of the correspondingantibody was added and left in a humid darkchamber overnight at +4 \u00b0C. The concentration of antibodieswas: 1:400, 1:800 \u2013 anti-D2R-AF647 sc-5303 and anti-TH-AF488 MAB318-AF488, respectively. Thereafter, the sampleswere washed in PBS-Tween, excess liquid was removed andplaced in ProLong, Glass Antifade Mountant, Thermo P36982(Thermo Fisher Scientific).Analysis of the density of neurons. Images were obtainedusing a confocal laser scanning microscope LSM 780 equipped with a Plan-Apochromat20x/0.8 M27 objective (Carl Zeiss) at the research facilitiesof the Center for Collective Use of Microscopic Analysis ofBiological Objects of the Siberian Branch of the Russian Academyof Sciences (https://ckp.icgen.ru/ckpmabo/) to estimatethe density of antibodies labeled neurons. The number of cellswas counted manually: without the use of special programsfor counting, in at least three sections per animal, in a fieldof view of 10 000 \u03bcm2 (one field of view per section). Sincethe VTA is a heterogeneous structure , we took sections throughout the entire area, whichcorrespond to a certain distance from the bregma, i. e., therostral part of the VTA \u20132.92 mm, the central part \u20133.16 mmand caudal part \u20133.28 mm according to the atlas . The ImageJ program was used to restrictthe field of view (10 000 \u03bcm2). The average number of cellsfrom three sections for each animal and the average volumedensity (mm3) were calculated.Statistical analysis. The analysis of the results was carriedout using the STATISTICA v. 12.0 software package. All data were tested for normality using theShapiro\u2013Wilk W-test. Data on the behavioral parameters arepresented as mean \u00b1 standard error of the mean (M \u00b1 SEM).Comparison between groups was performed using Student\u2019st-test. Data on neuron density are presented as a medianwith the first and third quartiles \u2013 Me . The densityof labeled neurons between groups was compared using theMann\u2013Whitney U-test. The significance level was taken atp <0.05.The preliminary testing of the control (C57BL/6J) andClstn2- KO mice before the start of the main experiment didnot reveal significant differences on the time spent in thecompartments with smooth and rough floor; thus the preference for a certain compartmentby mice of both studied groups was excluded. The results ofthe main test are presented in the Table. Mice of the controlgroup spent more time ( p < 0.05) in the socially associatedcompartment, where there was interaction with the conspecifics,compared with the compartment in which the individualwas previously alone. Meanwhile, Clstn2-KO mice spent thesame amount of time in both compartments. At the same time,animals from the Clstn2-KO group entered both parts of thechamber much more often ( p < 0.001), but spent less time( p < 0.05) in the socially associated compartment comparedto mice of the control group.Data on the density of VTA neurons labeled with D2R andTH antibodies are presented in Figures 1 and 2. Statisticalanalysis revealed a higher ( p < 0.001) density of neuronslabeled with anti-D2R and anti-TH in Clstn2-KO knockoutmice in the studied area as compared to controls.Previously, the social-conditioned place preference test wasalready used on mice of different strains . It was shown that normally theanimals spend more time in the compartment where they hadpreviously contacted conspecifics; these findings are consistentwith the notion that socially conditioned place preferencereflects social rewards . In our study,we examined social place preference as well as the density ofanti-D2R and anti-TH antibody-labeled neurons in the VTA ofClstn2-KO males and wild-type control (C57BL/6J) mice. Inthe social-conditioned place preference test, Clstn2-KO miceentered both compartments significantly more often, whichis apparently due to their higher level of locomotor activitycompared to the controls, which is consistent with the hyperactivityof these animals described in an earlier work . It is possible that Clstn2-KO mice, due to theirhyperactivity, were unable to form a reward caused by dailysocialization with a familiar partner, and as a result, wereunable to express their preference for the \u201csocial\u201d compartment.The observed impairment of social place preference inClstn2- KO mice is in good agreement with the previously reported impairment of social behavior for these mice .In our work, we focused on the study of neurons expressingD2R and TH in the VTA. In both Clstn2-KO and C57BL/6Jmice, the number of neurons labeled with anti-TH antibodieswas slightly higher than the number of neurons labeled againstD2R. This is apparently due to the fact that not only the DAneurons in which TH is found but also GABAergic neurons ofthe VTA express D2R . Meanwhile, we found more neurons with both D2Rand TH in the VTA of Clstn2-KO mice compared to controls.It was found that Clstn2-KO mice have more neurons containingD2R, as well as TH in the VTA compared to C57BLmice. Our data, as well as the results obtained on other strainsof mice modeling ASD ,indicate changes in the mesolimbic dopaminergic pathway,which also plays an important role in human ASD . In particular, in the work on mice of the BTBRstrain, despite the fact that they did not reveal functionalchanges in D1R in the striatum, a sharp decrease in D2R functionswas observed upon activation of DA neurons . Also, in Shank3 and Nlgn3-KO mice, a decreasein the activity of DA neurons in the VTA was revealed, whichcaused a behavioral deficit, including alterations of socialpreferences compared to C57BL controls . In another study, two strains of mice modelingdifferent forms of ASD were studied: BTBR and Fmr1-KO. A general decrease in tyrosine hydroxylaseexpression was found in the substantia nigra, VTA and striatumand in BTBR mice compared to C57BL mice, but not in theFmr1-KO strain . In a study of TKO mice,which is another model of autism, no changes were found inthe VTA DA neurons .Thus, ASD is often, but not always, associated with disturbancesin the DS in the VTA. A rather unexpected result isthat in Clstn2-KO mice the DS in the VTA is changed, but inthe direction of an increase in the number of neurons containingD2R and TH. The previously described hyperactivity ofClstn2-KO mice , which was corroboratedin the current work by the increased frequency of entering ofthe compartments in the social-conditioned place preferencetest, may be associated with an increased density of neuronsexpressing D2R. It has been shown in the hyperactive Colobomamice, that knockout of the D2R dopamine receptor generesulted in a decrease in locomotor activity compared to controls. Based on this, one may assume that theincrease in neurons with D2R in the VTA of Clstn2-KO micereported herein may be associated with an increased locomotoractivity of these animals. It is also interesting to note thathuman studies have shown that nucleotide polymorphism inthe D2R gene can be considered as a potential risk factor forthe development of not only ASD, but also attention deficithyperactivity disorder .It was previously shown that male Disc1-Q31L mice withdepression-like behavior, which were studied in the socialconditionedplace preference test, unlike Clstn2-KO mice,preferred the compartment associated with isolation . It can be assumed that this test adequately assessesthe alterations of social behavior different models ofmental disorders. Indeed, a depressive-like state caused bya deficiency of monoamines, including DA, is characterizedby a complete avoidance of social contacts, which was demonstratedfor the Disc1-Q31L strain .However, in our study on Clstn2-KO mice, which are a modelof ASD, results of this test were different. Nevertheless, wecannot completely exclude the effect of impaired spatial longtermmemory observed in the Morris test in Clstn2-KO mice on social preference, which needs to beconsidered in future studies.The data obtained may indicate a decrease in motivation forinteracting with conspecifics in mice with a knockout for theClstn2 gene, as the mice of this strain have not demonstratedpreferences to social-associated compartment. Also, changeswere found in the VTA, which plays an important role insocial preference ; in this brainstructure, an increased number of neurons expressing D2R andTH was found in Clstn2-KO mice. Thus, it can be assumed thatthe Clstn2 gene plays a certain role in dopamine-dependentprocesses of reward and motor activity, which may be associatedwith changes in the density of DA neurons in the VTA.The results of this study suggest that Clstn2 knockout mice,which can be considered as a model for studying autismspectrum disorders, demonstrate a change in the perception ofsocial reward and an increased number of neurons expressingdopamine type 2 receptors and tyrosine hydroxylase in oneof the important structures of the mesolimbic dopaminergicpathway \u2013 the ventral tegmental area, which is part of thereward system.The authors declare no conflict of interest.AlAyadhi L.Y., Hashmi J.A., Iqbal M., Albalawi A.M., Samman M.I.,Elamin N.E., Bashir S., Basit S. High-resolution SNP genotypingplatform identified recurrent and novel CNVs in autism multiplexfamilies. Neuroscience. 2016;339:561-570. DOI 10.1016/j.neuroscience.2016.10.030.Autism spectrum disorder. 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In addition, Hi-C can be used to detect chromosomal rearrangements, including balanced translocations and inversions. The use of the Hi-C method for the detection of chromosomal rearrangements is becoming more widespread. Modern high-throughput methods of genome analysis can effectively reveal point mutations and unbalanced chromosomal rearrangements. However, their sensitivity for determining translocations and inversions remains rather low. The storage of whole blood samples can affect the amount and integrity of genomic DNA, and it can distort the results of subsequent analyses if the storage was not under proper conditions. The Hi-C method is extremely demanding on the input material. The necessary condition for successfully applying Hi-C and obtaining high-quality data is the preservation of the spatial chromatin organization within the nucleus. The purpose of this study was to determine the optimal storage conditions of blood samples for subsequent Hi-C analysis. We selected 10 different conditions for blood storage and sample processing. For each condition, we prepared and sequenced Hi-C libraries. The quality of the obtained data was compared. As a result of the work, we formulated the requirements for the storage and processing of samples to obtain high-quality Hi-C data. We have established the minimum volume of blood sufficient for conducting Hi-C analysis. In addition, we have identified the most suitable methods for isolation of peripheral blood mononuclear cells and their long-term storage. The main requirement we have formulated is not to freeze whole blood. The combination of chromatin conformation capture methodswith whole genome sequencing led to the development ofa simple and efficient Hi-C protocol that allows genome-widestudying of chromatin architecture . In addition to the data concerning theorganization and dynamics of chromatin in the nucleus, theHi-C results showed that the relationship between three-dimensionaldistance in nuclear space and \u201cnucleotide\u201d distancein genomic coordinates can be described by a power functionfor all cell types. This means that chromosomal rearrangementshave effects not only on the contacts frequency of regionsdirectly located at the points of chromosome breaks, butalso change the pattern of three-dimensional contacts of a widearea around the rearrangement boundary . Chromosomal rearrangements detecting methodsbased on the analysis of the chromatine three-dimensionalorganization have recently been proposed . These methods detect various typesof rearrangements, including balanced ones, which are stilldifficult to detect by other methods . In addition, information about single nucleotidevariations can be obtained from Hi-C data , which is important for medical geneticsWhole blood is a common biological starting sample formedical genetics. Proper blood samples handling is criticalfor genome-wide studies. Long-term storage and inadequatestorage conditions lead to a decrease in the amount of isolatedDNA and its degradation . A high degree of DNA degradationis a serious problem for subsequent molecular biologicalanalyses .For example, an increase in the storage time of a blood sampleleads to an overestimation of the level of DNA methylation,which may be due to the different stability of methylated andunmethylated DNA .The key steps of the Hi-C protocol are chromatin fragmentationand ligation. To obtain high-quality datasets, it isnecessary that both of these steps take place in nucleus, underconditions of maximum preservation of the nucleus integrity.Thus, unlike DNA sequence analysis methods, the Hi-Cmethod imposes additional requirements on the quality of theinput material. In this regard, it seems relevant to determinethe appropriate storage conditions for blood samples intendedfor Hi-C analysis.Peripheral human blood was collected from the antecubitalvein into Vacutainer EDTA Blood Collection Tubes. Bloodsamples storage conditions and preprocessing steps are specifiedin the Table and Figure 1.The isolation of peripheral blood mononuclear cells(PBMC) from 3 ml of whole blood was performed using oneof the following methods:\u2022 Red Blood Cell Lysis Buffer was usedfor lysis of erythrocytes according to the manufacturer\u2019sinstructions. Then the cells were washed once with phosphatebuffer saline (PBS).\u2022 centrifugation 300 g for 10 minutes. Serum, including interphase,was transferred into PBS and centrifuged 300 gfor 10 minutes.sedimentation method on the density gradient Histopaque-1077 Hybri-max (Sigma) according to the manufacturer\u2019sinstructions.Cryopreservation of PBMC was performed in a cell freezingmedium: 10 % DMSO, 90 % KSR (Thermo Fisher Scientific).Cells were frozen at \u201380 \u00b0C and stored in liquid nitrogen. Afterthawing, the cells were washed once with PBS.Cells were counted and resuspended in PBS at a concentrationof 1 million cells/ml. Cell fixation, Hi-C library preparation,and data analysis were performed as described inGridina et al. (2021) using DNase I (Thermo Fisher Scientific)or S1 nuclease (Thermo Fisher Scientific) for chromatin fragmentation. HAPA Hyper prep and QIAseq\u00ae FX DNA LibraryKit (Qiagen) were used for NGS libraries preparation, accordingto the manufacturer\u2019s instructions. The DNA concentrationwas measured using a Qubit 3.0 fluorimeter (Thermo FisherScientific). NGS libraries were sequenced on HiSeq XTen(Illumina) with 150 bp paired reads.The first Hi-C step is cells fixation with paraformaldehyde,which is necessary to preserve the native spatial organizationof chromatin within the nucleus. Unfortunately, it is not alwayspossible to deliver the sample to the laboratory for fixation onthe blood collection day. We decided to systematically estimatethe impact of blood storage and preprocessing conditions onthe quality of the obtained Hi-C data. Ten conditions werechosen, which included: different methods of PBMC isolationfrom whole blood; different time and temperature of samplestorage; the possibility of freezing PBMC before fixing forlong-term storage .Although blood sampling is a minimally invasive procedurefor biomedical diagnostics, it is clear that there are certainlimits on the amount of blood that can be obtained from a patient.Especially if the patient is a small child, or has certainproblems with the blood coagulation system. Hi-C analysisrequires 1.5\u20132.5 million cells. Normally, 1 ml of blood contains(4\u201311) \u00d7 106 cells. To test each condition, 3 ml of wholeblood was taken in two replicates. The PBMC were counted after erythrocytes lysis but before cells fixation.A significantly higher number of cells were in the samplesprocessed according to condition #3 (isolation of nuclearelements without RBCL treatment). We did not determine theproportion of living cells during counting. It is possible thatdying cells were preserved in samples #3, whereas they werelysed in other cases using RBCL buffer orfreezing. Supporting the assumption, there were significantlyless cells in samples #4 and #10 that were not treated withRBCL but were frozen than in #2.There were no signs of hemolysis before the start of theisolation of PBMC for all samples except #6, and it was notpossible to evaluate this parameter for samples #6. Hemolysisshould be avoided, as it is one of the main factors negativelyaffecting the amount of DNA isolated from blood , which may be associated with DNA degradationby nucleases released from degrading cells.Cell conglomerates were formed in some samples duringerythrocyte lysis and subsequent washings. The conglomerateswere in both replicates in samples #6, #8, #9 and #10.For these samples, it was not possible to accurately count cellsand aliquot them uniformly.2.5 million fixed cells were taken to prepare Hi-C libraries.To assess the quality of Hi-C libraries ,the following controls were made: genomic DNA, DNA afterchromatin fragmentation and after ligation. All controls lookedaccepted .We sequenced the Hi-C libraries using paired-end reads witha length of 150 bp, mapped the paired-end reads to the humanhg19 genome (GRCh_37) and estimated quality metrics ofHi-C datasets. All libraries had a high proportion of alignedreads .Previously, we have shown that themost important quality metric of Hi-C datasets is the proportionof cis interactions ) . It reflects the proportion of Hi-C reads that mappedon the same chromosome among all Hi-C reads. The percentageof cis interactions was comparable for all libraries exceptsamples #6 where it was 40.3 and 35.7 %. It means that theseHi-C data are not informative as most fragments ligated randomly.Blood samples #6 were frozen without a cryoprotectantand stored for 4 days at \u201320 \u00b0C. The observed low percentageof cis interactions might be due to random DNA strandbreaks occurring when cells are frozen without cryoprotectants. On the other hand, this method of freezing leads toice crystals formation inside the cell and, as a result, to thebreaking of cellular and nuclear structures . Therelease of DNA fragments from the nucleus and their ligationin solution can occur in any way, which leads to the formationof non-informative DNA fragments.We systematically evaluated various blood samples storageand preprocessing conditions in this work.As a result, we formulated the following recommendationsfor the storage and preprocessing of blood samples for Hi-Canalysis:\u2022 If it is not possible to deliver the sample on the blood collectionday, the samples can be stored at +4 \u00b0C for a minimumof 7 days.\u2022 It is better to lyse red blood cells with RBCL buffer beforecryopreservation.\u2022 1\u20132 ml of whole blood is sufficient (in a person withoutsigns of leukopenia), but if the sample is going to be storedfor more than 48 hours, the volume should be increasedup to 4\u20136 ml.\u2022 Never freeze whole blood.The authors declare no conflict of interest.Al-Salmani K., Abbas H.H., Schulpen S., Karbaschi M., Abdalla I.,Bowman K.J., So K.K., Evans M.D., Jones G.D., Godschalk R.W.,Cooke M.S. 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(https://doi.org/10.1098/rspb.2020.2577)While conducting additional research on a similar topic, we discovered an error in the computation of relative fat content in the original article. In short, in the methods section, we describe the correct formula to calculate this: relative fat content = (dry weight \u2013 fat-free dry weight)/fat-free dry weight. However, we erroneously used fresh weight instead of dry weight to compute the relative fat content for our analyses, resulting in lower fat content values. We have repeated the analyses with the correct values for relative fat content and the mistake does not affect the results or conclusions of the article. Here, we present a new version of ReferenceProc. R. Soc. B287, 20202577 Issue: 1941. (doi:10.1098/rspb.2020.2577)1. Verspagen N, Ikonen S, Saastamoinen M, van Bergen E. 2020 Multidimensional plasticity in the Glanville fritillary butterfly: larval performance is temperature, host and family specific."} +{"text": "Scientific Reports 10.1038/s41598-022-24691-8, published online 22 November 2022Correction to: Aliza Fida was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cM.A., O.S. and F.A.T. conceived the idea of anti-reflecting metasurface for absorption. M.A. and O.S. analyze the results and wrote the manuscript. A.F, A.R. and F.A.T. performed simulations, fabrication and measurements. F.A.T. also contributed to the manuscript writeup and supervised the whole research.\u201dThe original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-023-33633-x, published online 20 April 2023Correction to: The Author Contributions section in the original version of this article contained an error, where the author Oliver Nelle was incorrectly identified as \u2018O.L.\u2019\u201cJ.S., S.M. and I.S. designed, analysed and interpreted the data and wrote the manuscript. O.L. and J.B. supported the analysis of the data as well as contributed to the manuscript writing. All authors read and approved the final manuscript.\u201dnow reads:\u201cJ.S., S.M. and I.S. designed, analysed and interpreted the data and wrote the manuscript. O.N. and J.B. supported the analysis of the data as well as contributed to the manuscript writing. All authors read and approved the final manuscript.\u201dThe original Article has been corrected."} +{"text": "Mage\u2009=\u200910.66\u00a0years; 55% female). The mean quality of the studies was rated as below average, although there were considerable differences between the studies. Overall, positive within-person changes during the treatment phase in comparison to the baseline phase were found. In addition, positive changes in the diagnostic status were observed at post- and follow-up treatment. Yet high variability in treatment effects was found between cases and studies. This meta-analysis harvests the knowledge from published single-case research in youth-internalizing disorders and illustrates how within-person information from single-case studies can be summarized to explore the generalizability of the results from this type of research. The results emphasize the importance of keeping account of individual variability in providing and investigating youth interventions.The effectiveness of interventions for internalizing disorders in children and adolescents was studied using a review and meta-analysis of published single-case research. Databases and other resources were searched for quantitative single-case studies in youth with anxiety, depressive, and posttraumatic stress disorders. Raw data from individual cases were aggregated and analyzed by means of multilevel meta-analytic models. Outcome variables were symptom severity assessed across baseline and treatment phases of the studies, and diagnostic status at post- and follow-up treatment. Single-case studies were rated for quality. We identified 71 studies including 321 cases (The online version contains supplementary material available at 10.1007/s10567-023-00432-9. Internalizing disorders such as anxiety, depressive, and posttraumatic stress disorders , are among the most common mental health problems in children and adolescents RCTs. As, to our knowledge, no meta-analysis on this topic has been conducted, the overall within-person treatments effects, its heterogeneity, and moderators that could potentially explain the heterogeneity are unknown for treatments of internalizing disorders in youth.This meta-analysis was driven by the fact that evidence of treatments for youth-internalizing disorders is mainly based on information on between-person effects from RCTs and the urge for information on within-person treatment effects and methods to study these. Further, while single-case studies are an acknowledged phenomenon in youth-internalizing intervention research, it is high time to start harvesting results of quantitative single-case research by systematically and quantitavely integrating its findings. Recent methodological developments, and collaborations between clinical researchers and methodologists make this endeavor possible. The aim of this meta-analysis is to provide a broad overview of the field and assess the overall within-person treatment effects, its heterogeneity and moderators that could explain this heterogeneity. As the single-case literature on internalizing disorders has not even been systematically reviewed yet, this study is exploratory in nature.https://osf.io/zjswg/?view_only=2b14c0d282e94a849f9d741a5cf759a1. Due to the unkown number and nature of potentially included studies, the analysis plan was pre-registered after the search and during data extraction. The meta-analysis was conducted according to the PRISMA guidelines , as a sufficient number of studies could be found on internalizing disorders in order to do a meta-analysis. This focus also made that we could limit the heterogenity between the studies to some extent. To include all current studies, a search was done in PsycInfo, Medline, and Web of Science with refined search criteria only including internalizing disorders in May 2021 for the period January 2020 to May 2021 and in February 2023 for the period May 2021 to February 2023. A full list of the original and refined search terms can be found in Supp1. In addition, Google scholar was checked for articles that were potentially missed and the references of all included studies were screened for possibly relevant studies. PsycArxiv and OSF were searched for gray literature in January 2021 and in February 2023.For the current meta-analysis, inclusion criteria were as follows: a quantitative Single-Case Design [SC(E)D] was used; participants were children (4 through 17\u00a0years old) who at the start of the study met DSM criteria for anxiety, depression or posttraumatic stress disorder; who received treatment aimed at reduction of internalizing symptoms; and results on symptom severity or diagnostic status were reported at least at one assessment point before and one assessment point after the treatment. We included studies involving both experimental, quasi-experimental, and non-experimental single-case designs as we wanted to safeguard power of these analyses and provide a complete overview of SC(E)D research on internalizing disorders in youth. Cases with an intellectual disability or an IQ below 70 and cases with a medical condition were excluded.The abstracts and the full texts of the studies were screened with the inclusion criteria by two independent raters. 20% of all abstracts and all full texts were double screened. Disagreement was resolved during discussion, through thorough checking of the inclusion criteria.The repeatedly assessed symptom severity across phases as depicted in individual graph data was the main outcome variable in this study. In most studies, only one main outcome variable was present. In studies where several variables were presented as outcome variables in graph data, one outcome variable was selected for the purpose of this meta-analysis, using the following criteria: (a) variable was related to the primary diagnosis ; and (b) the same variables were assessed across different studies . In most studies, main outcome variable was self-reported by the child . Parent-reported child symptoms were present in 42% of AD studies, 15% of MDD studies, and 12% of PTSD studies. The remainder of the outcome variables was rated by teachers or independent raters. Overall, behavioral outcome variables were parent and other reported . An overview of variables indicating symptom severity included in the analyses can be found in Supp3.Primary diagnosis , according to DSM III, IV, or 5, of the cases, on pre-, post-, and follow-up treatment was included as a categorical outcome variable (yes/no).Five potential moderators identified as important in previous studies on youth interventions coded for the analysis of the repeated assessments of symptom severity. First, the phase variable was coded into baseline and treatment phase. For studies which included a baseline and two different treatment phases referring to the same therapies with, e.g., different intensity or different techniques from CBT , the two treatment phases were taken together. Due to a lack of available data across studies, it was decided to not include data from follow-up phases in this analysis.Second, the time variable was coded such that it started at 0 at the beginning of the treatment and increased with 1 for each additional week. Third, the scores indicating the symptom severity were reverse coded for some studies so that a score decrease implies improvement for each study. Finally, to be able to combine and compare scores between studies and cases, symptom severity scores were standardized as proposed by Van den Noortgate and Onghena . This waTo meta-analyze the (standardized) data from all cases, a three-level linear regression model with symptom severity as the dependent variable and phase , time, and their interaction as predictors was estimated. Here, the intercept and the effect of the time can be interpreted as the expected level at the end of the baseline phase, and the time trend in the baseline phase, whereas the effects of the phase and the interaction term can be interpreted as the immediate treatment effect at the start of the intervention, and the effect the treatment has on time trend at the respective time point as the outcome variable. First, an intercept model was estimated to evaluate the overall probability of a diagnosis, separately for post-treatment and for follow-up. Subsequently, for moderator analysis, three models were estimated with age, disorder category, and target group as respective predictors, again in separate analyses for diagnostic status at post-treatment and at follow-up. Due to limited amount of data for diagnosis data, we limited this analysis to the three most important moderators. For all models, the intercept was allowed to vary between studies.102 studies matched the inclusion criteria. 27 studies were excluded due to unclarity about diagnostic procedures or absence of information about treatment outcomes on the case level. Four additional studies were excluded as the data in these studies could not be standardized for the purposes of multilevel meta-analysis. Thus, a total of 71 studies were included. From these 71 included studies, we still had to exclude 14 individual cases as they did not fit inclusion criteria, leaving a total number of cases of 321. A detailed overview of the study inclusion process is presented in PRISMA flow chart . Total number of dropouts was 12 and ranged from 0 (48 studies) to 6 (1 study); 7 studies did not report on drop out. Mean age of the cases was 10.66\u00a0years ; 55% of the cases were female (for about 50 cases gender was not reported or only on a sample level). For about 30% of the cases, no information regarding ethnicity or cultural background of participants was reported (Supp3). In 22% of the cases, no information about comorbidity was reported. In 18% of the cases, no comorbidity was observed. Comorbidity with another internalizing disorder was present in almost 40% of the cases, with an externalizing disorder in 4%, and with ADHD and ASS in 18% and 4% of the cases, respectively. 4% of the cases had other comorbid disorder .A summary of study characteristics is presented in Supp3 wherein case-level information on all variables can be found. Number of cases per study ranged from 1 to 17 , 3.17 , and 8.89 , respectively. In Supp3, quality scores of (sub)scale(s) for each study can be found.Length of the treatment in weeks ranged between 0.02 (3-h treatment) and 68\u00a0weeks. On average, the treatments consisted of 10.47 sessions, ranging from 1 to 36 sessions. Overall, average scores for the total RoBiNT scale, and internal and external validity subscales were 12.06 a significant immediate reduction of the symptom severity at the start of the treatment phase; b\u2009=\u2009\u2212\u00a00.67, 95% CI\u2009=\u2009, p\u2009=\u20090.002. The symptom severity significantly reduced with 0.14 standard deviation per week during the baseline phase; b\u2009=\u2009\u2212\u00a00.14, 95% CI\u2009=\u2009, p\u2009=\u20090.031. The linear decrease in symptoms became more pronounced during the treatment phase when compared to the baseline phase as indicated by the interaction between phase and time; b\u2009=\u2009\u2212\u00a00.27, 95% CI\u2009=\u2009[\u2212 0.47\u20130.07], p\u2009=\u20090.005, resulting in a reduction of 0.41 (=\u2009\u2212\u00a00.14\u20130.27) standard deviation per week during the treatment phase. These analyses were re-done excluding three studies that were concerned with medication treatment and one study concerned with animal-assisted therapy, respectively , there was much variation for the intercept between the studies (the estimated standard deviation \u03c4 \u2009=\u20093.17) and cases (\u03c4\u2009=\u20092.19). This shows that the symptom severity was very different between cases and studies at treatment start. Also the treatment effects varied considerably between studies and cases. Between the studies, the effect of phase varied with \u03c4\u2009=\u20091.14 and the effect of phase*time varied with \u03c4\u2009=\u20090.59. Given the assumption that effects are normally distributed across studies, this would mean that for 95% of the studies, the immediate treatment effect ranges between \u2212\u00a02.90 and 1.56, and that the effect is negative for 72% of the studies. For the effect on the time trend (phase*time), the 95% prediction interval is with a negative effect for 68% of the studies. Between cases, the effect of phase varied with an estimated standard deviation \u03c4\u2009=\u20091.49 and the effect of phase*time with \u03c4\u2009=\u20090.36. These results suggest that for 95% of the cases and a typical study, the immediate effect varies between \u2212\u00a03.59 and 2.25 (with 67% of the effects being negative), and the effect of phase*time varies between -0.98 and 0.44, and that the effect is negative for about 77% of the cases. Figure\u00a0r\u2009=\u2009\u2212\u00a00.75. This indicates that the larger the symptom severity at the end of the baseline, the more pronounced is the symptom severity reduction in the treatment phase compared to the baseline phase.Moderators The results for the three-level regressions which include the moderator variables are displayed in Supp6. Almost none of the variables showed a significant effect on the baseline level or trend in symptom severity, nor on the immediate effect of time trend (interaction with phase and time respectively). Only the immediate symptom reduction during the treatment phase seems to be more pronounced for cases with PTSD when compared to cases with AD or MDD; b\u2009=\u2009\u2212\u00a01.16 , p\u2009=\u20090.027.n\u2009=\u200976) cases still met diagnostic criteria for AD, MDD, or PTSD. At follow-up, 21.99% (n\u2009=\u200942) cases still met diagnostic criteria for AD, MDD, or PTSD. Results of all multilevel logistic regressions can be found in Table Data on diagnostic status were available for 268 cases from 62 studies at post-treatment and 191 cases from 44 studies at follow-up. At post-treatment, 28.46% and disorder category (p\u2009=\u20090.08 for post-treatment and p\u2009=\u20090.85 for follow-up). Still, the average likelihood of a diagnosis at post-treatment and follow-up is indicated to be below chance also when age, target group, or disorder category is taken into account, see Table Age does not seem to have an effect on the diagnosis probability, both for post-treatment and follow-up of RCTs as they are based on within-person comparisons and tested in a wide range of individuals. These positive results are informative from the clinical point of view as the majority of the sample concerned referred cases that are in general characterized by high severity and comorbidity and harder to be treated. This hypothesis was not quantitatively tested in this meta-analysis, but our impression of the treatments utilized in included studies is that at least in the half of the studies treatments were tailored to some client characteristic. For example, in some studies, treatments were tailored to a specific age group , condition , or symptom . Potentially, this may have impacted the positive results. In addition, this might have also perhaps influenced rather low dropout rates of cases in the studies included in our meta-analysis.One of the most important findings concerns the \u2018variability\u2019 of case characteristics and individual treatment effects. Our results showed that cases and studies are very heterogeneous; there are differences between the cases (within the same study) in demographics, and differences between the studies in designs, type of treatments, number of sessions, and length of treatment Supp3). In line with this, although overall positive, treatment effects largely varied between cases and studies Figs.\u00a0 and 3. T. In lineNext to the limited amount of studies, a notable limitation of our study is that, in graph data analysis, both child and other report of the outcome variable were included, based on the availability in the studies. It seems that more behavioral symptoms were always rated by others in the included studies. Despite different reporters, the current meta-analysis offers the first overview of quantitative single-case research on internalizing youth and provides empirical evidence for an overall positive within-person treatment effect and considerate heterogeneity between studies and cases for this treatment effects. With the surge of single-case research in internalizing youth, future meta-analyzes will be able to better evaluate moderators explaining the variability of individual treatment effects.were fulfilled , but this information was not explicitly reported in the specific article. While high-quality guidelines exist for conducting . Our general impression was that at least in some studies criteria In sum, this is, as far as we know, the first study that explored the generalizability of treatment effects found in single-case research in youth treatment outcome studies by meta-analyzing during-treatment within-person changes. Overall, a positive impact of treatments was found for youth-internalizing disorders and symptoms, and the estimated effect was positive for the majority of cases and studies. Yet we also found a large variability between studies and cases in their characteristics and treatment effects. 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Supplementary file1 (DOCX 13 kb)Below is the link to the electronic supplementary material."} +{"text": "Dear Editor,The high diagnostic potential of urinary extracellular vesicles (uEVs) for urogenital disease has been recognized for more than a decade. This is emphasized by the identification of different molecular biomarkers in uEV preparations that may assist the clinical management of prostate, bladder, and renal cancer published a position paper summarizing the current state of the art and listing detailed recommendations for improved rigor, reproducibility and inter\u2010operability in uEV research position paper (Thery et\u00a0al., positionSTORAGE of urinary EVs (Figures\u00a0To support the implementation of the published recommendations, and enhance their application in daily research practices, here we provide a Quick Reference Card on Figures\u00a0. The Qui Figures\u00a0. The Car Figures\u00a0 and acco Figures\u00a0. The CarTo conclude, we present a novel format of communication for EV study guidelines and recommendations that can also be applied to other topics within, but importantly also outside the field of urinary EVs. Ultimately, by using this format, we endeavor to enhance adherence to pre\u2010analytical best practice guidelines in order to promote reproducibility and, above all, the translational potential of uEV studies.The authors report no conflict of interest.Conceptualization: M.v.R., C.S., C.G., J.W., T.T., M.D., A.B., B.G., A.L., C.B., D.B., U.E., E.M.U. Writing, original draft preparation: M.v.R., E.M.U.; Writing, review and editing: M.v.R., C.S., C.G., J.W., T.T., M.D., A.B., B.G., A.L., C.B., D.B., U.E., E.M.U.All authors have read and agreed to the published version of the manuscript.Supplementary File 1. Quick Reference Card: Storage of Urinary EVsClick here for additional data file."} +{"text": "Dipteran parasitoids of Embioptera (webspinners) are few and extremely rare but known from all biogeographical regions except Australasia/Oceania. All belong to the fly family Tachinidae, a hyperdiverse and widespread clade of parasitoids attacking a variety of arthropod orders.Embiophoneus rossi gen. et sp. nov. The genus Perumyia Arnaud is reviewed and a new species, Perumyia arnaudi sp. nov., is described from Central America while P. embiaphaga Arnaud is redescribed and new host records are given. A new species of Phytomyptera Rondani, P. woodi sp. nov., is described from Myanmar, representing the first report of a member of this genus obtained from webspinners. The genus Rossimyiops Mesnil is reviewed, R. longicornis (Kugler) is redescribed and R. aeratus sp. nov., R. fuscus sp. nov. and R. rutilans sp. nov. are newly described from the Oriental Region, and an updated key to species is given.The webspinner-parasitizing Diptera are reviewed based mostly on records from the collecting and rearing by Edward S. Ross. A new genus is erected to accommodate a new Afrotropical species, Webspinners were probably colonized independently at least four times by tachinids shifting from other hosts, most likely Lepidoptera.The online version contains supplementary material available at 10.1186/s40850-022-00116-x. Webspinners\u2014Embioptera, Embiodea or Embiidina \u2014are an aWebspinners are among the least collected insects largely because of their cryptic lifestyle. As their common name implies, these insects\u2014adults as well as nymphs\u2014produce silk using glands in their protarsi and spin retreats or, in some species, elaborate maze-like galleries in which they spend virtually their entire lives. They are herbivorous, lichenophagous or detritivorous and construct their galleries on the bark of trees, under stones, in leaf litter, and in other places that afford them access to such food sources as lichens, moss, bark and dead leaves , 11. TheA major contributor to our knowledge of the Embioptera was Edward S. Ross (1915\u20132016), who published on this group over a period of approximately 70\u2009years. He was an avid collector who travelled the world in search of webspinners. He eventually amassed a collection of about 350,000 specimens housed in the California Academy of Sciences in San Francisco (CAS) . On veryPerumyia embiaphaga Arnaud in Peru / Liberia: 10\u2009mi. N. / Gbanka 25.XI. / 1966 E. S. Ross // Collection of the California Academy of Sciences, San Francisco, Calif. based on the combination of setulose prosternum, strong first postsutural supra-alar seta, convex facial ridge with a row of strong setae above vibrissa and cerci not fused medially. The dissected female had no eggs stored in uterus; thus, it is not possible to ascertain whether Embiophoneus is micro- or macro-ovolarviparous .Remarks The male shows all diagnostic characters of Perumyia embiaphaga, except for vein R4\u2009+\u20095 bearing two setae at base instead of six, which likely represents intraspecific variability.Perumyia arnaudisp. nov.LSID urn:lsid:zoobank.org:act:4DB1244A-179C-4D28-85CA-FDE3188F7B2D.Diagnosis Body length about 4\u20135\u2009mm. Frons at its narrowest point as wide as compound eye in dorsal view (both sexes). Second aristomere 3.5\u20134.0 times as long as its diameter. Apical scutellar setae absent. Vein R4\u2009+\u20095 with short setae from base approximately halfway to crossvein r-m. Bend of vein M1 with a stub longer than crossvein r-m. Abdomen brown and partly reddish laterally, tergites 3 and 4 with pruinosity on anterior 1/3.Description Body length: 4.7\u2009mm. Color or yellowish . Postpedicel mostly dark brown shading into yellowish at junction with pedicel. Palpus yellowish. Thorax dark brown. Presutural area with whitish pruinosity except on four dark vittae. Upper and lower calypters whitish. Wing veins brown or yellowish. Tegula black and basicosta yellow. Legs brown in ground color. Scutellum mainly brown with pruinosity. Abdomen brown and partly reddish laterally. Tergites 3 and 4 with pruinosity on anterior 1/3. Terminalia brown. Head Fig. c; apicaling Fig. e, f. Cosing Fig. f. Vein Rmen Fig. a, b. TerDistribution Mexico, Nicaragua.Hosts Embioptera: unidentified species of Mesembia Ross (Anisembiidae) (Mexico) and Neorhagadochir Ross (subgenus Drepanembia Ross) (Scelembiidae) (Nicaragua).Etymology The species is dedicated to the entomologist Paul H. Arnaud in recognition of his contribution to our knowledge of Tachinidae.Type material Holotype \u2642: HOLOTYPUS \u2642 / Perumyia / arnaudi sp. nov. / Badano et al. det. 2021 // Nicaragua: 31 mi. / NW Esteli, 2000\u2009ft. / 29-Nov-1976 / Host: Drepanembia // Fly matured 18-Nov- / 1976 / Ex Drepanembia, / Edward S. Ross. // Collection of the California Academy of Sciences, San Francisco, Calif. , strong rows of both reclinate orbital setae and proclinate setae on facial ridge. Distichona includes 8 species , by monotypy.Diagnosis Small to medium-sized flies, body length 2\u20135\u2009mm. Frons of equal width or slightly wider than compound eye width in dorsal view (both sexes). Arista thickened at least on basal 2/3. Second aristomere 3\u201310 times as long as wide. Upper part of head with several rows of black setae behind postocular row . Prosternum setulose. Three postsutural intra-alar setae. Proepimeral seta curved downward. Scutellum with strong, convergent, subparallel or slightly diverging, subapical setae, apical setae present but very small. Vein R4\u2009+\u20095 with a single large seta at base. Vein M1 with bend evenly curved or with apical section obliterated. Cell r4\u2009+\u20095 not petiolate.Distribution All biogeographic regions except Australasia/Oceania.Hosts Lepidoptera Apodytrisia . Embioptera (new record).Included species See O\u2019Hara et al. n. sp. // Collection of the California Academy of Sciences, San Francisco, Calif. // Phytomyptera sp. / det: D. M. Wood, 2012 [CAS] , as follows: wing vein M1 reaching wing margin (M1 not reaching wing margin in P. minuta), crossvein dm-m present (absent in P. minuta) and black palpus (yellow in P. minuta). species . However species \u201329. Despevidence . The relTachininae, MinthoiniRossimyiops Mesnil, 1953Rossimyiops Mesnil, 1953: 145. Type species: Rossimyiops whiteheadi Mesnil, 1953, by monotypy.Diagnosis Small tDistribution Palaearctic: Southeastern Europe n. / sp. // Collection of the California Academy of Sciences, San Francisco, Calif. [CAS] Persedea exquisita Richter, 2001: 28. Type locality: Tehran (Iran).Mesnilomyia rufipes Zeegers 2007: 411. Type locality: 12\u2009km NW of Manakhah (Yemen).References Cerretti et al. n. / sp. // Collection of the California Academy of Sciences, San Francisco, Calif. [CAS] Mesnilomyia longicornis Kugler, 1972: 108. Type locality: \u1e94efat (Israel).References Cerretti et al. Rossimyiops magnificus Mesnilomyia magnifica Kugler, 1972: 105. Type locality: 'Arad (Israel).References Cerretti et al. n. sp. / Edward S. Ross // Collection of the California Academy of Sciences, San Francisco, Calif. means \u201cthat shines in red\u201d. It should be treated as a Latin adjective.Rossimyiops subapertus Mesnilomyia subaperta Herting 1983: 5. Type locality: Anbar-Abad (Iran).References Cerretti et al. ........................................10Parafacial at its narrowest point about 3\u20134 times as wide as maximum diameter of arista. Thorax (including scutellum) and femora black, coxae varied from black to reddish, palpus basally yellowish-brown, shading into black distally. Abdomen black. Wing slightly smoky anteromedially and along veins. Ventral seta of mid tibia weak and shorter than maximum diameter of mid tibia ...................Modified from Cerretti et al. .Wing veiR. austrinus unknown]10.1 between crossveins r-m and dm-m distinctly shorter than section between dm-m and bend of vein M1. Cell r4\u2009+\u20095 with petiole more than 0.5 times as long as postangular section of vein M1 .......................R. longicornis (Kugler)Face flat, ventral facial margin not visible in lateral view. Prementum about 2\u20133 times as long as its diameter. Postpedicel 2.5\u20133.0 times as long as pedicel. Wing hyaline. Section of vein MFrons at least as wide as compound eye in dorsal view , with two or more proclinate orbital setae, frontal vitta not as above [females] ..................121. Cell r4\u2009+\u20095 with petiole 0.3\u20130.5 (rarely more) times as long as postangular section of vein M1 ..................1111.R. achilleae (Kugler)Wing anteriorly brownish. Postpedicel 1.9\u20132.2 times as long as pedicel. Body length: 2.5\u20133.5\u2009mm ...........................................................................Ventral facial margin well visible in lateral view, anterior to vibrissal angle. Prementum about 4\u20135 times as long as its diameter. Postpedicel 1.7\u20132.2 times as long as pedicel. Wing hyaline or brownish anteriorly. Section between crossvein r-m and dm-m approximately as long as section between dm-m and bend of vein MR. magnificus (Kugler)12.Postpedicel 1.0\u20133.1 times as long as its diameter. Wing from hyaline to brown ........................................13Wing hyaline. Postpedicel 1.7\u20131.9 times as long as pedicel. Body length: 4.5\u20136.0\u2009mm ........13.Postpedicel as long as pedicel. Fronto-orbital plate with dark vitta really wide on medial margin, between row of proclinate orbital setae and compound eye. Calypter whitish. Wing hyaline, slightly yellowish .........................................................................undescribed species #3 from Nigeria (CNC)Postpedicel 5 times as long as its diameter. Wing hyaline .........undescribed species #2 from Nigeria (CNC)14.R. longicornis (Kugler)Face flat, ventral facial margin not visible in lateral view. Postpedicel 2.7\u20133.1 times as long as pedicel. Prementum about 2\u20133 times as long as its diameter. Wing from white to smoky anterodistally. Calypter varied from brownish with a slightly darker rim to evenly dark brown. Halter yellow to light brown .........................Postpedicel 1.7\u20133.1 times as long as pedicel. Wing from hyaline to brown. Fronto-orbital plate not as above. Calypter from white to dark brown ................1415.R. austrinus CerrettiFrons about 0.5 times as wide as compound eye in dorsal view. Parafacial, in lateral view about 0.5\u20130.6 as wide as postpedicel. Fronto-orbital plate with dark stripe on its medial margin, between the row of proclinate orbital setae and setae and the frontal vitta. Ventral facial margin well visible in lateral view, anterior to vibrissal angle, protruding by about the distal width of antennal pedicel. Halter black. Wing membrane slightly infuscate anteriorly. Coxae black. Abdomen shiny black, without whitish pruinosity. Postpedicel 2.0\u20132.5 times as long as pedicel\u00a0......................................................Ventral facial margin visible in lateral view, anterior to vibrissal angle. Postpedicel about 1.7\u20132.5 times as long as pedicel. Prementum about 4\u20135 times as long as its diameter. Wing not as above. Calypters white to yellowish. Halter yellow to black ..................................1516.R. achilleae (Kugler)Postpedicel 1.7\u20132.5 times as long as pedicel. Body length: 2.5\u20133.5\u2009mm .........................Frons at least 0.6 times as wide as compound eye in dorsal view. Parafacial, in lateral view, 0.7\u20131.0 times as wide as postpedicel. Fronto-orbital plate entirely and evenly covered with whitish pruinosity. Ventral facial margin not so strongly protruding. Halter yellow to dark brown. Coxae light brown, red to yellowish. Abdomen shiny black to entirely covered with microtrichia. Postpedicel 1.68\u20132.47 times as long as pedicel .....................................16R. magnificus (Kugler)Postpedicel 1.7\u20131.9 times as long as pedicel. Body length: 4.5\u20136.0\u2009mm .....................[male of Remarks The three new species described here, R. aeratussp. nov., R. fuscussp. nov. and R. rutilanssp. nov., represent the first records of Rossimyiops from the Oriental Region. The new species differ from their congeners by the presence of one strong seta on the posterior margin of the hind coxa and inner vertical setae crossed.R. longicornis (Kugler) that emerged from webspinners reared by Ross confirm the association of Rossimyiops with webspinners, an interaction previously known only for R. exquisitus and R. whiteheadi [R. longicornis and we also observed this in the specimens we examined.Our report of five specimens of iteheadi . Cerrettiteheadi and Kugliteheadi remarkedSericobracon Shaw (Braconidae), in which one species (and possibly another) is an endoparasitoid of the clothodid Antipaluria urichi (Saussure) [Embidobia Ashmead, Palaeogryon Masner and Embioctonus Masner), which include egg endoparasitoids of webspinners [Only two insect orders include parasitoids of webspinners: Diptera and Hymenoptera. These two hyperdiverse clades account for the vast majority of insect parasitoids, with the latter much more diverse in this respect. The parasitism of webspinners by Hymenoptera has evolved independently at least three times: once in the small chrysidoid family Sclerogibbidae, the members of which are obligate ectoparasitoids of embiopteran nymphs , 42; oncaussure) ; and at spinners \u201346. The spinners hypothesspinners .Loewia Egger (and relatives) and Spilochaetosoma Smith apparently switched to chilopods and scorpions from lepidopteran-associated ancestors [Phytomyptera species often attack concealed larvae of micromoths [Phytomyptera woodi is the only known species of its genus with a non-lepidopteran host. Minthoini also include species developing on concealed larvae of Lepidoptera, however hosts are unknown for most of the species, hinting at possibly unusual hosts for many of them. Graphogastrines and minthoines lay membranous eggs ready to hatch, and the planidial larvae actively seek for hosts. Members of the Goniini reach their hosts in a different way. They lay tiny \u201cmicrotype\u201d eggs on the food of their hosts that are ingested by the feeding host. The eggs hatch in the gut and the first instar larvae migrate into the host haemocoel to complete development. As a rule, goniines parasitize phyllophagous caterpillars and, more rarely, sawfly larvae by laying their eggs along leaf margins, in particular those which have been chewed by hosts. To our knowledge, only a few goniines have switched to non-leaf feeders. These include several species of the genera Pexopsis Brauer & Bergenstamm and Erythrocera Robineau-Desvoidy, and the species Manola xenocera Richter and Masistyloides kononenkoi Richter, which all develop in adult beetles, Arama gobica Richter which develops in cockroaches [Ocytata pallipes which is a parasitoid of earwigs, and several species of Allophorocera Hendel which develop in crane fly larvae [Pseudalsomyia Mesnil [Perumyia and Embiophoneus, which also attack concealed, non-phyllophagous hosts that usually do not leave their shelters. The discovery of the trophic strategies of any of these aberrant goniines may shed light on the evolutionary path that has led to these bizarre host shifts in this megadiverse tribe.Parasitoids of webspinners within Diptera evolved only in the Tachinidae, the largest and most successful of all dipteran lineages of endoparasitoids. Recent reconstructions of the evolution of host preferences in this family suggest that the last common ancestor of tachinids likely developed on soil-dwelling invertebrates, and the clade later radiated and diversified on various phytophagous insect lineages through a series of host shifts , 49. Somncestors . A suddencestors , 50. Thencestors . This huricidae) , 29. Phyy larvae . Despitea Mesnil because Embiophoneus and Perumyia), probably once in the graphogastrine genus Phytomyptera, and once in the minthoine genus Rossimyiops. This specialization likely evolved in each lineage from ancestors sharing similar habits such as attacking silk-protected or concealed hosts or searching microhabitats like those occupied by webspinners.Tachinids shifted to webspinners at least four times: twice in the huge tribe Goniini (The dissection of male terminalia was carried out following the protocol described in detail by O\u2019Hara . DigitalTerminology of external morphology follows Cumming & Wood , measurehttp://zoobank.org/\u201d, LSID: urn:lsid:zoobank.org:pub:62FDC19C-3D03-48F9-B92F-C8CDCFB71D3B.This publication and its nomenclatural acts have been registered in ZooBank \u201cAbbreviations for depositories cited in this work are as follows: CAS \u2013 California Academy of Sciences, San Francisco, California, USA; CNC \u2013 Canadian National Collection of insects, arachnids and nematodes, Ottawa, Canada; MZUR \u2013 zoological museum, Sapienza University, Rome, ItalyData labels of the holotype specimens are shown as Additional file Additional file 1:\u00a0Figure S1 Holotypes labels."} +{"text": "Diagnostic and therapeutic management of the thoracic outlet syndrome. Review of the literature and report of an Italian experience By Camporese G, Bernardi E, Venturin A, Pellizzaro A, Schiavon A, Caneva F, Strullato A, Toninato D, Forcato B, Zuin A, Squizzato F, Piazza M, Stramare R, Tonello C, Di Micco P, Masiero S, Rea F, Grego F, Simioni P (2022). Front. Cardiovasc. Med. 9:802183. doi: 10.3389/fcvm.2022.802183A Corrigendum on In the published article, there was a mistake in the caption of Figure\u00a01. The correct caption is as follows:Figure 1. Anatomical spaces involved in TOS. Originally published in \u201cThe human spring approach to thoracic outlet syndrome\u201d. Author: Dr. James Stoxen DC FSSEMM (hon); illustrated and copyrighted by Body Scientific International, LLC \u2013 www.BodyScientific.com. Permission of the Author with agreement signed in February 2022.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-023-28552-w, published online 24 January 2023Correction to: The original version of this Article contained errors in the spelling of the author Vajira H.W. Dissanayake, which was incorrectly given as Vajira H.W. Dissnayake.The original Article has been corrected."} +{"text": "Epidermolysis bullosa (EB) is an inherited disorder of skin fragility, caused by mutations in a large number of genes associated with skin integrity and dermal-epidermal adhesion. Skin fragility is manifested by a decrease in resistance to external mechanical influences, the clinical signs of which are the formation of blisters, erosions and wounds on the skin and mucous membranes. EB is a multisystemic disease and characterized by a wide phenotypic spectrum with extracutaneous complications in severe types, besides the skin and mucous membranes, with high mortality. More than 30 clinical subtypes have been identified, which are grouped into four main types: simplex EB, junctional EB, dystrophic EB and Kindler syndrome. To date, pathogenic variants in 16 different genes are associated with EB and encode proteins that are part of the skin anchoring structures or are signaling proteins. Genetic mutations cause dysfunction of cellular structures, differentiation, proliferation and apoptosis of cells, leading to mechanical instability of the skin. The formation of reduced proteins or decrease in their level leads mainly to functional disorders, forming mild or intermediate severe phenotypes. Absent protein expression is a result of null genetic variants and leads to structural abnormalities, causing a severe clinical phenotype. For most of the genes involved in the pathogenesis of EB, certain relationships have been established between the type and position of genetic variant and the severity of the clinical manifestations of the disease. Establishing an accurate diagnosis depends on the correlation of clinical, genealogical and immunohistological data in combination with molecular genetic testing. In general, the study of clinical, genetic and ultrastructural changes in EB has significantly expanded the understanding of the natural history of the disease and supplemented the data on genotype-phenotype correlations, promotes the search and study of epigenetic and non-genetic disease modifier factors, and also allows developing approaches to radical treatment of the disease. New advances of sequencing technologies have made it possible to describe new phenotypes and study their genetic and molecular mechanisms. This article describes the pathogenetic aspects and genes that cause main and rare syndromic subtypes of EB. Epidermolysis bullosa (EB) is a group of rare and currentlyincurable genetically determined hereditary skin diseases. Thedisease is characterized by fragility of the skin and mucousmembranes that occurs with mechanical trauma, seeminglyinsignificant in terms of shear force, often accompanied bydamage to nails, teeth and hair . Thespectrum of characteristic skin manifestations is wide andincludes blisters, erosions, wounds that can become chronic,scarring, crusting, milia, skin atrophy, and dyspigmentation.In rare subtypes, it is possible not only to damage the skin, butalso muscles, the gastrointestinal tract, kidneys, etc., which isdue to the nature of the expression of the defective protein.The severity of the disease varies from phenotypically mildto severe disabling or lethal variants, which determines theexpected prognosis of life expectancy. Severe EB subtypesdevelop as systemic diseases with secondary multiple organdamage and developmental delay, anemia, affect heart andbones, movement disorders, early susceptibility to skin cancer,and premature death. The treatment of EB is exclusivelysymptomatic and is aimed at the prevention of mechanicalinjuries, wound care, treatment of infectious complicationsand extracutaneous manifestations of the disease. To date,no therapeutic approaches have been able to cure EB patients.Epidermolysis bullosa is a demonstrative model of mechanobullousdisease, and the study of the underlying mechanismshas made it possible to make significant progress in understandingthe fundamentals of the physiology and pathophysiologyof the skin. The gained knowledge about EB was reflectedin the classification, which was revised several times overthe past decade by an international consensus group . Epidermolysis bullosa is divided into four maintypes \u2013 simplex EB (EBS), junctional EB (JEB), dystrophicBE (DEB) and Kindler\u2019s syndrome (KS), which is based onthe ultrastructural changes and the level of blisters in the skinand reflects the consequences of genetic defects on the proteinfunction. Epidermolysis bullosa is clinically and geneticallyvery heterogeneous, inherited in an autosomal dominant (AD)or autosomal recessive (AR) pattern of inheritance . Advances in understanding the pathogenesis of EBcontribute to the development of potentially effective protein,cell and gene therapies .The epidermal basal layer, basement membrane zone (BMZ)and extracellular matrix are key subregions that take centralplace in the pathophysiology of EB andgenetic changes disturb the structure or function of their proteins. Pathogenic variantsin 16 differentgenes determine the genetic and allelic heterogeneityof EB and the grouping of four main types of EB, includingmore than 30 clinical subtypes. EB-associated genes encodeintracellular, transmembrane or extracellular proteins,mainly structural components of the cytoskeleton (keratin 5and 14), BMZ orintercellular adhesion proteins (see the Table) .Table presents the key processes of pathogenesisleading toa certain phenotype.Simplex EB (EBS) is the most common type, accounting forabout 70 % of all patients with EB , andincludes 14 clinical subtypes according to the latest classification.Simplex EB has a wide range of severity, from mildwith blistering of the palms and feet to generalized forms withextracutaneous lesions, sometimes fatal . SimplexEB is most often caused by defects in the keratin filaments ofbasal keratinocytes, has a different genetic basis: it is associatedwith changes in at least seven genes and represents thegreatest clinical diversity.Most subtypes of EBS are inherited in the AD pattern,although AR inheritance occurs in some regions of the world. The mostcommon EBS subtypes observed in clinical practice arecaused by mutations in the keratin 5 or 14 genes (70\u201380 % ofcases), while according to the literature data, at least 17 % ofpatients with EBS had mutations de novo . In addition, EBS with ADinheritance may be associated with heterozygous variants inthe PLEC or KLHL24 genes . Rare digenic inheritance caused by mutations in theKRT5 and KRT14 genes have also been described in patientswith EBS .Keratin 5 and keratin 14 have a similar protein structureconsisting of a central \u03b1-helical rod domain that is responsiblefor the polymerization of these proteins to form keratin tonofilaments.The core domain is subdivided into segments 1A,1B, 2A and 2B by flexible linkers L1, L12 and L2, flanked byvariable domains V1 and V2 in both proteins. Also, keratin 5 has a conserved H1 and H2 homology domain. The KRT5and KRT14 genes are expressed in the basal keratinocytes ofthe epidermis, where their protein products combine to formheterodimeric molecules. The K5 and K14 dimers are themain components of the keratinocyte intermediate filamentsystem, which assemble into an intracellular network .Among the pathogenic variants in the KRT5 and KRT14genes predominate dominant missense variants that affectthe ability of keratins to interact with their partner. The locationsof the pathogenic variant in the functional domains ofthe KRT5 or KRT14 genes are of key importance . Dominant-negative pathogenic variants are grouped atthe beginning of 1A or the end of 2B segments of the helicalrod domain of KRT5 and KRT14 and are typical of severegeneralized EBS, because these domains are highly conservedand are considered critical for filament assembly.The most common pathogenic variants are: p.Glu477Lys inthe KRT5 gene and p.Arg125Cys, p.Arg125His, p.Asn123Serin the KRT14 gene . In moderate EBS, pathogenic variants are located inthe second part of segments 1A or 2B of the core domainof KRT5 and KRT14. In this subtype, they do not alter theprocess of keratin elongation during filament assembly, but impair their function . In thelocalized EBS subtype, pathogenic variants are clustered inboth KRT5 and KRT14, usually outside the highly conservedcore domain boundary motifs, as well as in L12 linkers, inaddition, in the KRT5 gene in the H1 domain, causing structuralinstability of the filaments . Moredistinct correlations with the genotype were found in the EBSsubtype with spotted pigmentation, which is associated withpathogenic variants in the V1 domain of the KRT5 gene, sothe p.Pro25Leu variant accounts for 90\u201395 % of mutations inthis subtype .Severe and moderate EBS with AR inheritance is associatedwith rare pathogenic biallelic variants in KRT14 and KRT5,which are found in consanguineous families . Homozygous mutations in the KRT5 gene result ina severe phenotype, extracutaneous manifestations, and earlymortality .The latest revision of the EB classification characterizedrare syndromic EBS subtypes associated with mutations inthe PLEC, KLHL24, DST, EXPH5, and CD151 genes (seethe Table); we will consider them below.The plectin protein encoded by the PLEC gene is a cytoskeletalprotein that links the network of intermediate filamentsto HD and thus acts as a mediator of the mechanical stabilityof keratinocytes in the skin . A large numberof alternatively spliced first exons of the plectin gene formmultiple protein isoforms and determine different expressionin tissues, which ensures clinical diversity and leads to fourrare EBS phenotypesPathogenic variants in the PLEC gene were mainly foundin exons 31 and 32, loss-of-function variants leading to moresevere phenotypes such as EBS with pyloric atresia (EBS-AP)and, as a result of null variants of the PLEC gene, EBS withmuscular dystrophy (EBS-MD), where skeletal muscle fiberslose their structural integrity due to defects in desmin filaments. Moderate EBS with AR inheritance is causedby a specific homozygous nonsense mutation p.Arg16X inthe first exon encoding the plectin 1a isoform, resulting inthe absence of only this specific isoform . Also, in exon 31 of the PLEC gene, a dominant aminoacid substitution p.Arg2110Trp was described, which leadsto a partial loss of protein function and causes HD fragmentation, which is clinically manifested asmoderate EBS.The KLHL24 protein belongs to a family of highly conservedproteins with BTB/kelch domains; pathogenic variantsin the KLHL24 gene lead to dysregulation of autoubiquitinationand change the regulation of degradation of keratin 14 mo-leculesand cause its fragmentation . Inthe EBS subtype caused by mutations in the KLHL24 gene, inall described cases, a heterozygous variant was observed in thestart codon, the most common being c.1A-G with a dominantnegative effect . Also, 85 % of patientswith this subtype of EBS at a young age develop dilatedcardiomyopathycaused by KLHL24-mediated degradationof desmin, the main protein of cardiomyocyte intermediatefilaments .Dystonin (BPAG1) is a member of the plakin protein family. The DST gene encodes the epithelialBPAG1-e isoform, which is a structural component of internalHD plaques and consists of a helical-helical rod domain andflanking N- and C-termini. The N-terminus of the BPAG1-eprotein is involved in its integration into HD and has bindingsites for type XVII collagen and \u03b24 integrin, while theC-terminus is the key point of attachment of keratin intermediatefilaments . Mutations in BPAG1-ehave been shown to be associated with impaired adhesion ofkeratinocytes, increased cell migration with reduced expressionof \u03b24-integrins on the cell surface .Clinically, it leads to a mild phenotype.The exophilin-5 protein, a RAB27b GTPase effector proteinencoded by the EXPH5 gene, is not a structural componentof intermediate filaments, desmosomes, or PD. Although itsrole is not fully known, it is assumed that it contributes tothe regulation of intracellular transport of vesicles, includingthe control of their formation and movement along the actinand tubulin networks, as well as the secretion of exosomes. Single families are described with homozygousvariants in the EXPH5 gene, leading to a frameshift,as well as in combination with nonsense variants. Mild clinicalmanifestations have been described.In the epidermis, the expression of the transmembraneprotein CD151 is localized in HD, binding to \u03b16\u03b24 integrinand stabilizing its interaction with laminin-332, and playsa critical role in the formation of the \u041dD complex. CD151mediates cell adhesion and intracellular vesicular transportof integrins. In the kidneys, it forms complexes with \u03b13\u03b21and \u03b16\u03b21 integrins and is required for the correct assemblyof glomerular and tubular basement membranes . A defect in the CD151 protein determines theclinical manifestations in individuals with CD151-associatedEBS, including nephropathy with proteinuria .Junctional EB (JEB) is also a clinically and geneticallyheterogeneous group of skin fragility disorders, includes nineclinical subtypes, and is a rare type of EB .JEB subtypes have pathognomonic signs, for example, in severegeneralized subtype, granulation tissue is rapidly formedin typical places, and mortality is high .Phenotypic variability in JEB is extremely wide \u2013 from onlynail dystrophy to death in the first year of life. Pathogenic variantsin seven different genes lead to the development of JEB,all subtypes are inherited in the AR type. Pathogenic variantsin the LAMA3, LAMB3, and LAMC2 genes encoding the \u03b13,\u03b23, and \u03b32 chains of laminin-332, as well as in the COL17A1gene, encoding type XVII collagen, lead to the most commonJEB subtypes . Rare JEB phenotypes areassociated with deficiency of a6\u03b24 integrin, leading to thedevelopment of JEB with pyloric atresia and deficiency ofthe \u03b13 subunit of a3\u03b21 integrin, causing EBS with respiratoryand renal involvement .The laminin-332 protein is a heterotrimer consisting of \u03b13,\u03b23, and \u03b32 chains, which are encoded by the LAMA3, LAMB3,and LAMC2 genes, respectively. Together with the extracellulardomain of type XVII collagen, they form anchor filaments.The laminin-332 protein binds at its \u03b1-chain C-terminusto \u03b13\u03b21 integrins in focal adhesion sites and \u03b16\u03b24 integrinsin HD, connecting the surface of basal keratinocytes to the dermal-epidermal BM . In the dermis, theN-terminus of laminin-332 chains bind to type VII collagen,so that anchor filaments and anchor fibrils connect directly. Loss of laminin-332 expressioncauses extreme skin fragility and excess granulation tissue ingeneralized severe JEB. In laminin-332-deficient JEB subtypes,the LAMB3 gene is altered in 70 % of cases. Approximately9 % of patients with JEB have mutations in the LAMA3and LAMC2 genes, respectively . The most common pathogenic variant is p.R635X,as a \u201chot\u201d mutation point, which accounts for 45\u201363 % of allpathogenic alleles of the LAMB3 gene in generalized severeJEB, resulting in the absence of one of the three proteins thatare assembled in laminin-332.Mild manifestations of EB are caused by missense mutations,splicing site mutations, and deletions with preservationof the reading frame, which, leading to a change in the keypositions of protein subunits, affect the ability of laminin \u03b13,\u03b23, and \u03b32 to assemble into a trimeric molecule, its secondarystructure, and its ability to form intracellular anchor fibrils.A special phenotype, laryngo-onycho-cutaneous syndrome(LOC syndrome), manifests pathogenic variants that forma stop codon in exon 39, specific for the alpha-3 subunit ofthe LAMA3 gene, where three causative variants have beendescribed so far: p.V51fs; p.Gln157Ter; p.Trp16Ter . Recently, C. Prodinger et al. (2021) reportedthree new mutations in the LAMA3 gene outside of exon 39.Type XVII collagen protein is a homotrimer consistingof three identical subunits, is a transmembrane protein andthe main structural component of PD, has both intracellularand extracellular domains. Type XVII collagen acts as a cellsurface receptor for extracellular matrix proteins . The extracellular domain of typeXVII collagen is associated with laminin-332; in this regard,it takes part in the creation of anchor filaments, can controlcell motility, determines the spatial orientation of laminin-332and its location in the collagen-IV-containing lamina BM.This protein also regulates the differentiation of ameloblasts,epithelial cells involved in the formation of tooth enamel. Enamel defects, ranging from punctateto generalized hypoplasia, occur in all subtypes of JEB,arising from impaired adhesion of the odontogenic epitheliumfrom which ameloblasts originate .Also, type XVII collagen plays a central role in regulatingthe proliferation of the interfollicular epidermis, participatingin the maintenance of hair follicle stem cells, where it controlstheir aging program, which may explain the irreversible hairloss in people with type XVII collagen deficiency .Pathogenic variants in the COL17A1 gene usually resultin moderate JEB , although a fewfatal cases have been described with the presence of pathogenicCOL17A1 variants . Accordingto D. Kiritsi et al. (2011) 69 % of the COL17A1 gene variantswere nonsense variants, insertions or deletions, 19 %were missense variants, and 12 % were splice site variants.Pathogenic variantsleading to exon skipping in the COL17A1gene have a mitigating effect on the phenotype, allowing theproductionof a sufficiently functional protein .In some cases, nonsense mutations can cause mild manifestationsof moderate generalized JEB due to alternative splicingmechanisms. It was shown that in patients with a homozygousnonsense mutation p.R795X in exon 33, COL17A1 mRNA isformed as a result of alternative splicing, which allows theproduction of a small amount of type XVII collagen.Integrins are heterodimeric transmembrane receptors consistingof \u03b1- and \u03b2-subunits that form a functional receptor. In the epidermis, \u03b13\u03b21, \u03b16\u03b24, and\u03b12\u03b21 integrins are the most abundant. The \u03b16\u03b24 integrin bindsto laminin-332 and to keratin filaments within the cell, whichallows it to coordinate the cellular response and regulate adhesion,migration, and proliferation of keratinocytes. The \u03b16\u03b24integrin is also involved in the formation of HD integrity andstability and interacts with type XVII collagen, plectin, anddystonin . The group of \u03b21-integrinsis associated mainly with the basal surface of keratinocytesand is involved in the formation of focal contacts. The \u03b13\u03b21integrin is found both on the basal and lateral surfaces ofbasal keratinocytes, where it can participate in intercellularcontacts.The ITGA6 gene encodes the \u03b16 subunit, the ITGB4 geneencodes the \u03b24 subunit of the \u03b16\u03b24 integrin. Pathogenic variantsin these genes, leading to premature termination oftranslation, form a severe phenotype that can be fatal in theneonatal period. Most of the mutations are in the ITGB4 gene;splicing site variants, small deletions and insertions, aminoacid substitutions that lead to a rare subtype, JEB with pyloricatresia, have been described . Studiesof genotype and phenotype correlations indicate that variantslocated in the extracellular domain of ITGB4 are usually associatedwith a more severe phenotype compared to thoselocated in the cytoplasmic tail . In theITGA6 gene, single variants with loss of function in patientsfrom consanguineous families are described, which are clinicallymanifested by early manifestation and often with a fataloutcome .The ITGA3 gene encodes the \u03b13 integrin subunit, which isassociated with the \u03b21 subunit and forms the \u03b13\u03b21 integrininvolved in interactions with extracellular matrix proteins, includinglaminins. The \u03b13 integrin subunit is expressed in basalkeratinocytes, podocytes, tubular epithelial cells, alveolarepithelial cells, and many other tissues .Several cases of JEB with interstitial lung disease and renalabnormalities have been reported, associated with pathogenicvariants in the ITGA3 gene, the expression of which in differenttissues explains the multiple organ damage observed inpatients. In addition, the relationship between the \u03b13 integrinsubunit and the cell membrane is complex, including posttranslationalmodifications, cleavage, heterodimerization withthe \u03b21 integrin subunit, and association with CD151. Aminoacid substitutions can interfere with these events and act asnull mutations, leading to severe disease ;variants that express a residual, truncated, or dysfunctionalprotein may result in a milder phenotype and improved survival.Dystrophic EB (DEB) is divided into two main groups:dominant DEB (DDEB) and recessive DEB (RDEB). Clinical diversity includes 11 subtypes, with all subtypes havingcutaneous and extracutaneous manifestations of varying severity.In general, RDEB is more severe than DDEB, rangingfrom severe skin manifestations with scarring and fibrosis,secondary complications, extracutaneous manifestations, anda high risk of squamous cell carcinoma, to mild skin fragilityon the extremities or only nail dystrophy. However, there is asignificant phenotypic overlap between AD and AR subtypes,which often makes it clinically difficult to establish the typeof inheritance of DEB in a patient, especially if the probandis the only patient in the family.DEB develops as a result of mutations in only one gene,the COL7A1 gene, which encodes type VII collagen, the mainprotein of anchor fibrils that provide BM attachment to theunderlying dermis. Pathogenic variants in the COL7A1 genelead to a disruption in the production and molecular structureof collagen, causing splitting of the upper layers of the dermisand destruction of anchor fibrils. The nature and location ofpathogenic variants are important determinants of the phenotype, which is determined by theexpression and residual function of collagen VII .Type VII collagen is a non-fibrillar collagen synthesizedby both epidermal keratinocytes and dermal fibroblasts andis localized in the BM zone below the epithelial layers, representinga homotrimer consisting of three identical \u03b11 polypeptidechains . Each \u03b11 polypeptide chaincontains a central collagen triple helix domain and terminalnon-collagen NC-1 and NC-2 domains .The triple helical domain consists of a repeating Gly-X-Ysequence interrupted by non-collagenous regions, the largestof which consists of 39 amino acid residues and is known asthe \u201chinge\u201d region.The NC-1 domain mediates the attachment of anchorfibrils to the basement membrane and islets of collagen IVin the dermis . The NC-2domain contains conserved cysteines involved in the formationof disulfide bonds, which provide a link between type VIIcollagen homotrimers. In addition, loops formed by anchorfibrils in the papillary dermis capture and mechanically holdinterstitial collagen fibers, which are mainly represented bycollagen types I, III and V.Also, type VII collagen promotes the migration of keratinocytes,which is one of the stages of wound healing, providingtheir re-epithelialization . It has beenshown that in DEB the size or number of anchor fibrils isreduced, or they are absent , whichdetermines the main mechanism and severity of the developmentof clinical manifestations. Impaired function of type VIIcollagen leads to deep skin defects, scarring of the mucousmembranes, the formation of milia and fibrosis.Hundreds of mutations in the COL7A1 gene associatedwith DEB are known . Thus, most cases of DDEB are the result of dominantnegativemutations. Approximately 75 % of DDEB patientshave glycine substitution variants in the Gly-X-Y triple helicaldomain, especially in exons 73, 74, and 75 . At this hotspot, glycine residue substitutions can leadto greater protein destabilization than glycine residue substitutionswithin a long, continuous collagen segment, and variantsnear the hinge region cause protein misfolding and accumulationwithin cells . It is also suggested thatexon 73 may encode amino acid residues important for theability of type VII collagen to provide keratinocyte motility.Glycine as well as other amino acid substitutions and splicingvariants outside the Gly-X-Y region are also found inDDEB, and intrafamilial phenotypic variability suggests thatother factors may influence cell resistance to friction .Severe generalized RDEB usually results from the absenceof a COL7A1 gene product resulting in null genetic variantson both alleles, about 30 % of which are nonsense stop codonor splicing variants resulting in large deletions, determiningdisease severity . Many patientswith moderate RDEB are compound heterozygous for a prematurestop codon and glycine substitution in the collagendomain, another missense variant or variants that disruptsplicing, resulting in destabilization of the triple helix or conformationalchanges in the protein that affect its functionality.This variety of combinations of genetic variants explainsthe wide range of clinical manifestations. So, for example,p.Gly2049Glu and p.Arg2063Trp variants, adjacent to the\u201chinge\u201d region, reduce the ability to maintain fibroblast adhesionand lead to a significantly reduced ability to supportkeratinocyte migration, which slows down the healing oferosions in RDEB patients . Milder formsof RDEB are often caused by a combination of splicingand missense variants. Glycine substitutions may also occurin RDEB.Kindler syndrome (KS) is a rare type of EB characterizedby skin fragility and acral blistering from birth, developmentof skin atrophy, photosensitivity, poikiloderma, diffuse palmoplantarhyperkeratosis, and pseudosyndactyly . Morphologically, KS differs from other typesof EB in that blistering is variable and can occur at differentlevels of the dermal-epidermal junction. KS develops as aresult of pathogenic variants in the FERMT1 gene. The diseaseis inherited according to the AR type.The FERMT1 gene encodes the Kindlin-1 protein, which isa multidomain focal adhesion protein. Kindlin-1 is involvedin the connection between the actin cytoskeleton and theextracellular matrix through focal adhesion, as well as inintegrin-associated signaling pathways . Theabsence of Kindlin-1 leads to disorganization of keratinocytesas a result of incorrect integrin-mediated cell adhesion andmigration . More than 90 pathogenicloss-of-function variants have been registered in the FERMT1gene, including: missense, nonsense, and splicing variants;insertions; and Alu-mediated gene rearrangements that resultin the absence of the Kindlin-1 protein or the production ofa non-functional protein . Environmentalfactors play an important role in the phenotypicdiversity of KS and determine the severity. X. Zhang et al.suggested that homologue 1 of the fermitin family is importantfor the suppression of UV-induced inflammation and DNArepair .The multisystem manifestations of EB and the involvementof a significant number of proteins that provide mechanicalstability of the skin in the pathogenesis are due to its geneticheterogeneity. Pathogenic variants in the genes encodingproteins of the epidermal and dermal anchoring complexes,as well as signal proteins that determine the integrity of theskin, lead to their structural and functional defects. EB ischaracterized by pronounced clinical variability and, at thesame time, similar manifestations in different genotypes. Researchand accumulation of the data of the natural history ofdisease and the genotype-phenotype correlations contribute tounderstanding the EB pathogenesis and determine the developmentof approaches for symptomatic and etiopathogenetic, inparticular, gene therapy.The authors declare no conflict of interest.Arin M.J., Grimberg G., Schumann H., de Almeida H. Jr., Chang Y.- R.,Tadini G., Kohlhase J., Krieg T., Bruckner-Tuderman L., Has C.Identification of novel and known KRT5 and KRT14 mutations in53 patients with epidermolysis bullosa simplex: correlation betweengenotype and phenotype. Br. J. Dermatol. 2010;162(6):1365-1369.DOI 10.1111/j.1365-2133.2010.09657.x.Asaka T., Akiyama M., Domon T., Nishie W., Natsuga K., Fujita Y.,Abe R., Kitagawa Y., Shimizu H. Type XVII collagen is a key playerin tooth enamel formation. Am. J. Pathol. 2009;174(1):91-100. 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DOI 10.1074/JBC.M709452200.Wright J.T., Carrion I.A., Morris C. The molecular basis of hereditaryenamel defects in humans. J. Dent. Res. 2015;94(1):52-61. DOI10.1177/0022034514556708.Zhang X., Luo S., Wu J., Zhang L., Wang W.-hui, Degan S., ErdmannD., Hall R., Zhang J.Y. KIND1 loss sensitizes keratinocytesto UV-induced inflammatory response and DNA damage. J. Invest.Dermatol. 2017;137(2):475-483. DOI 10.1016/J.JID.2016.09.023."} +{"text": "Martin et al., RSC Chem. Biol., 2023, https://doi.org/10.1039/D3CB00020F.Correction for \u2018Radiolabeling and The authors regret the omission of a funding body associated with the work. J. A. M. and J. A. C. acknowledge funding from the US Department of Energy (DE-SC-0021007 to J. A. C.).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "It is known that different species of animals, when living in the same environmental conditions, can form similar phenotypes. The study of the convergent evolution of several species under the influence of the same environmental factor makes it possible to identify common mechanisms of genetic adaptation. Local cattle and sheep breeds have been formed over thousands of years under the influence of domestication, as well as selection aimed at adaptation to the local environment and meeting human needs. Previously, we identified a number of candidate genes in genome regions potentially selected during domestication and adaptation to the climatic conditions of Russia, in local breeds of cattle and sheep using whole genome genotyping data. However, these data are of low resolution and do not reveal most nucleotide substitutions. The aim of the work was to create, using the whole genome sequencing data, a list of genes associated with domestication, selection and adaptation in Russian cattle and sheep breeds, as well as to identify candidate genes and metabolic pathways for selection for cold adaptation. We used our original data on the search for signatures of selection in the genomes of Russian cattle and sheep breeds. We used the HapFLK, DCMS, FST and PBS methods to identify DNA regions with signatures of selection. The number of candidate genes in potentially selective regions was 946 in cattle and 151 in sheep. We showed that the studied Russian cattle and sheep breeds have at least 10 genes in common, apparently involved in the processes of adaptation/selection, including adaptation to a cold climate, including the ASTN2, PM20D1, TMEM176A, and GLIS1 genes. Based on the intersection with the list of selected genes in at least two Arctic/Antarctic mammal species, 20 and 8 genes, have been identified in cattle and sheep, respectively, that are potentially involved in cold adaptation. Among them, the most promising for further research are the ASPH, NCKAP5L,SERPINF1, and SND1 genes. Gene ontology analysis indicated the existence of possible common biochemical pathways for adaptation to cold in domestic and wild mammals associated with cytoskeleton disassembly and apoptosis. The impact of extreme environmental factors can lead to eitherthe extinction of a species or its adaptation to new environmentalconditions . It is known that differentanimal species, inhabiting similar conditions, can developsimilar phenotypes using similar biochemical pathways . Studying convergent evolution of several species underthe influence of the same environmental factor allows for theidentification of common genetic adaptation mechanisms.For example, the same non-synonymous mutation in therhodopsin gene independently arose and was subjected toselection in at least 20 species of fish in response to changesin water light conditions . The convergentamino acid substitutions also occurred in the prestin gene ofwhales and bats during the evolution of echolocation . The non-synonymous substitution His207Arg in themelanocortin 1 receptor gene is associated with light feathercoloration in red-footed boobies and ruffs . Our recent work on the northernmost cattle, the Yakutcattle from Siberia, revealed the phenomenon of convergentnucleotide evolution among domestic breeds and wild speciesliving in similar harsh conditions and/or exhibiting similarphenotypes. We found the same amino acid substitution in theNRAP protein in Yakut cattle and 16 species of cold-adapted,hibernating or deep-diving mammals, which was absent inall other breeds of cattle and other Bovinae species in the\u201c1000 Bull Genomes\u201d dataset . Accordingto our data, this amino acid substitution presumablyarose 500\u2013800 years ago and is almost fixed in the modernYakut cattle population.It is known that the domestication of animals of differentspecies is accompanied by a number of similar morphophysiologicaland behavioral changes . For example, one of the typical morphological featuresof domestication is the disruption of melanin synthesis, aswell as a slowing down of melanocyte development, leadingto the appearance of white spots on the body, up to theemergence of a uniform white color .Such phenotypic parallelism is observed in cattle, horses,pigs, dogs, cats, minks, chickens, pigeons, etc. . Indeed, when studying the genomes of populations ofdomestic animals, strong selection signals have been foundin melanin metabolic pathway genes .Local breeds of cattle and sheep have been formed overthousands of years under the influence of domestication, aswell as natural and artificial selection directed towards adaptationto the factors of the local environment and meetinghuman needs .Studying the genomes of local breeds of cattle allows for theidentification of genetic mechanisms of adaptation, includingto low temperatures of the surrounding environment . Earlier, we identified a number of candidate genesin genome regions that were potentially subject to selectionduring domestication and adaptation to harsh climatic conditionsin Russia, in local breeds of cattle (Bos taurus) and sheep(Ovis aries) using data from whole-genome genotyping onstandard SNP arrays . Based onthese results, we also identified 31 common candidate genesrelated to adaptation to the environment, including cold climate,in animals of the studied breeds .For example, the NEB gene, probably associated with heatproduction through shivering thermogenesis, was identifiedby us in genome regions subject to positive selection both innative Russian breeds of cattle and sheep, as well as in thegenomes of the mammoth, polar bear, and minke whale.However, whole-genome genotyping data have low resolutionand do not allow the detection of most nucleotide substitutionsin the genomes of different agricultural animal species.The aim of this study was to create a list of common genesassociated with environmental adaptation in Russian breedsof cattle and sheep, as well as to identify promising geneticvariants/candidate genes/metabolic pathways for further experiments,marker-assisted and genomic selection aimed atcold adaptation in agricultural animals, using whole-genomesequencing data. Previously, we analyzed selection signaturesin the DNA samples from Yakut, Kholmogory, and Buryatcattle using GeneSeek Genomic Profiler High-Density SNParray containing approximately 139,000 SNPs , and from Baikal and Tuva sheep using OvineInfinium HD SNP BeadChip .In the study, we used our own published data on the searchfor selection signatures using whole-genome sequencing inthe genomes of Russian or bred in Russia cattle breeds and sheep . High-throughput sequencing was performed inpaired-end mode (150 bp + 150 bp) on the Illumina platformat Novogene Co., Ltd. for 20 animalsper breed. The average coverage depth was at least 11x forcattle and 15x for sheep.To identify regions potentially under selection pressurein the genomes of Buryat and Wagyu cattle, we used fourcomplementary methods . The hapFLKmethod is based on statistics that consider haplotype structurein populations . The DCMS methodcombines five whole-genome statistics: Fisher\u2019s fixation index(FST), haplotype homozygosity (H1), modified haplotypehomozygosity (H12), Tajima\u2019s D index (D), and nucleotidediversity index (Pi) . The FST method identifiesgenome regions subject to selection by identifying DNAsegments with high allelic frequency variability betweencompared populations . The PBSstatistic uses pairwise FST values between three populationsto quantitatively assess sequence differentiation . It is considered that genes with high differentiationbetween sequences may potentially be under positive selection.Candidate gene lists for further analysis of Buryat andWagyu cattle were compiled by combining lists obtained bydifferent methods. Potential selection regions in the genomesof Yakut and Kholmogory cattle breeds were identified usinghapFLK statistics . For the search forselection signatures in the genomes of Baikal and Tuva sheep,a computational pipeline based on the DCMS method wasused .Gene identifiers in the Ensembl database were convertedinto gene symbols using the db2db tool ). Intersections between gene listswere analyzed using the Venn program (http://bioinformatics.psb.ugent.be/webtools/Venn/).Biological functions of the shared genes that were underselection in Russian cattle and sheep breeds, and Arctic/Antarcticmammals were analyzed using the DAVID web tool. We identified enriched GO terms fromthe category of biological processes (GOTERM_BP_ALL)associated with four or more genes, compared to the controllist of all human genes. We used a significance thresholdcriterion, characterized by the statistical significance of theobserved number of genes with a specific GO term comparedto the expected number of genes from the control list, andaccepted p < 0.05 as the threshold value.The number of candidate genes in regions potentially subjectedto selection was 946 for four Russian cattle breeds 1 and 151 for two Russian sheepbreeds (see the Table). The difference in the number of candidate genes between speciesis likely due to differences in the number of breeds includedin the analysis, as well as the number of statistical methodsused to detect signatures of selection . Analysis of theintersection of the lists showed that 10 genes could potentiallyhave been under selection in both species .http://vavilov.elpub.ru/jour/manager/files/Suppl_Yudin_Engl_27_5.pdfSupplementary Materials are available in the online version of the paper:Previously, by intersecting the lists of genes potentiallysubjected to selection in six Arctic and Antarctic mammalspecies, we compiled a list of genes that may be involvedin cold adaptation . The list contained416 genes that were likely under selection in at least twomammal species .To identify common genes that may be associated withadaptation to cold climate in Russian cattle and sheep breeds,we compared the lists of List_Mammals, List_Cattle, andList_Sheep. As a result, we found 20 and 8 genes that were potentially under selection in at least two wildmammal species adapted to cold climate as well as in cattleand sheep, respectively .To test the hypothesis that these lists were enriched infunctional categories of genes related to cold adaptation, weperformed gene ontology (GO) analysis on a list of 38 genesobtained by merging the Cattle_Sheep, Cattle_Mammals,and Sheep_Mammals lists . As a result, we found significant enrichment ineight GO terms that were associated with 4 or more genes.Our study aimed to identify common candidate genes in thegenomes of domestic cattle and sheep breeds in Russia thatmay have undergone selection and played a role in adaptationto extreme climates, as well as to identify promising geneticvariants/candidate genes/metabolic pathways for further coldadaptation research. We identified a total of 10 genes thatpotentially could have been under selection simultaneouslyin both Russian cattle and sheep breeds . These genes were likely subjected toselection during domestication and/or subsequent selectionfor economically important traits, as well as during adaptationto cold climates.According to the theory of D.K. Belyaev, numerous morphophysiologicaltransformations in domestic animals arecaused by destabilizing selection for the absence of aggressivebehavior towards humans . Indeed, wehave previously shown that a list of 1262 common genesthat underwent selection in Russian cattle and sheep breedsthrough whole-genome genotyping was enriched in genespredominantly expressed in the brain .Several common genes identified in our study are expressed in nervous tissue and are involved innormal neuron function. For example, the protein astrotactin 2(ASTN2) modulates synaptic activity in neurons by regulatingthe expression of synaptic proteins in post-migratory neuronsvia endocytosis . Genetic variants in theASTN2 gene are associated with Alzheimer\u2019s disease , schizophrenia ,autism , and other psychiatric disorders.The gene encoding the protein containing a peptidase domainM20 1 (PM20D1) is associated with Alzheimer\u2019s disease and Parkinson\u2019s disease . The transmembrane protein TMEM176A gene isassociated with schizophrenia .At the same time, deletion in the ASTN2 gene results ina reversal of normal orientation of hair follicles in adult mice to the opposite direction . In humans,the ASTN2 gene is associated with the level of triglycerides inthe blood and the development of obesity. Signatures of selection in this gene havebeen found in ethnic groups of southern Ethiopia, who havelived in high-altitude conditions for over a thousand years. Interestingly, adaptive introgressionof a large number of ancient Neanderthal alleles has beenidentified in the ASTN2 gene in the population of South Asia. The biochemical pathway of PM20D1 modulates the accumulation of brown fat and thus participatesin the process of heat production through non-shiveringthermogenesis . The pro-adipogenicfactor GLIS1 may play a critical role in the differentiationof mesodermal cells during fetal development and affectfat distribution in the tail of sheep . SNPpolymorphism in the NSG1 gene is associated with the fatcontent in milk of Holstein cows .We investigated promising genetic variants and candidategenes for cold adaptation by intersecting the lists List_Cattleand List_Sheep with the List_Mammals of 416 genes that werepositively selected in at least two species of Arctic/Antarcticmammals . When all three lists of commongenes and genetic variants were intersected, none were found, but we identified 20 and 8 genes , respectively, that were potentially subjectedto selection during adaptation to the climate of both Arcticmammals and cattle or sheep, respectively.Thus, genetic variants in the ASPH gene, which encodesa protein that regulates the process of excitation\u2013contractionin muscles, are associated with heat stroke and malignanthyperthermia in humans . Accordingto whole-genome association analysis, single nucleotidepolymorphisms in this gene are associated with intramuscularfat distribution in beef cattle .Genetic variants in the NCKAP5L andSERPINF1 genes are associated withthe development of obesity in humans. The human geneFAM184B is associated with body composition and fattyacid profile . The protein product of thePADI3 gene controls hair shape on the human scalp . The mRNA expression of the gene of the proteincontaining the staphylococcal nuclease domain 1 (SND1) inthe New Zealand alpine stick insect significantly increases inresponse to cold exposure . In mammals,SND1 plays an important role in regulating lipid metabolismthrough the activation of the SREBP2 protein .The gene ontology terms identified by the DAVID programwhen analyzing the list of potentially selected genes in Russiancattle, sheep, as well as Arctic/Antarctic mammals can be divided into three groups:(1) terms related to the disassembly of cell parts and proteincomplexes ; (2) terms related to DNA disintegration(\u201chydrolysis of phosphodiester bonds in nucleic acids\u201d);(3) uninformative terms of the top hierarchy describing generalbiological processes .Enrichment of gene ontology terms related to thedisassembly of cell parts, proteins, and DNA may be theresult of natural selection for genes encoding cytoskeletalproteins and/or participating in programmed cell death(apoptosis). Studies on hibernating mammals have shown thattheir cells respond to low temperatures by disassembling thecytoskeleton and delaying apoptosis . It is believed that cytoskeletal disassembly may be thecause of protein synthesis suppression in mammalian cellsduring cold stress . Hypothermiacauses disassembly of microtubules by activating p38 MAPkinase in human retinal cells . In in vivoand in vitro experiments, it has been shown that microtubulesin peripheral axons of Xenopus are sensitive to cold, and theirdensity varies depending on the season .It has been shown that cold stress induces apoptosis of neuronsin the hippocampus of mice .In our study, the term \u201cdisassembly of cellular components\u201dwas associated with seven genes .Among them, the gene SPTBN5 encodes one of the spectrinfamily proteins, which are common components of thecytoskeleton, interacting with elements of the cell scaffoldand plasma membrane, providing proper localization ofmajor membrane proteins, signal transmission into the cell,and other processes . The proteinNCKAP5L, interacting with the protein CDK5RAP2,regulates microtubule stability in HeLa cells . The protein stathmin-3, encoded by the STMN3 gene,regulates the rapid reorganization of the cytoskeleton inresponse to environmental factors by affecting the balanceof microtubule assembly and disassembly . With the term \u201chydrolysis of phosphodiester bondsof nucleic acids\u201d, genes RCL1, CECR2, SND1, and DCP1Bwere associated . It has been shownthat the SND1 protein suppresses apoptosis in hepatocellularcarcinoma cells by interacting with the long non-coding RNAUCA1 . The CECR2 protein is localized inthe DNA condensation regions of apoptotic human liver cellsand interacts with the chromatin-associated protein TAFII30.Thus, using whole-genome sequencing data, we have shownthat the studied Russian cattle and sheep breeds have atleast 10 common genes, presumably involved in adaptation/selection processes, including adaptation to cold climate,such as ASTN2, PM20D1, TMEM176A, GLIS1. Based on theoverlap with the list of genes subjected to selection in at leasttwo species of Arctic/Antarctic mammals, 20 and 8 genespotentially involved in adaptation to cold were identifiedin cattle and sheep, respectively. Among them, the mostpromising for further research are the genes ASPH, NCKAP5L,SERPINF1, and SND1. 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High-densitygenotyping reveals signatures of selection related to acclimationand economically important traits in 15 local sheep breeds fromRussia. BMC Genomics.2019;20(Suppl.3):294. DOI 10.1186/s12864-019-5537-0."} +{"text": "Crocus, series Verni, were discovered. The species was compared to the morphologically related C. veluchensis, and presented with diagnostic morphological and anatomical features. Despite the high degree of morphological similarity, the molecular analysis, which included sequences from all related species , distinguished the Pirin Mountains\u2019 populations, and revealed the closest relationship to C. heuffelianus. Despite the C. heuffelianus/C. verni complex\u2019s uncertain taxonomic status, our findings on the local population, based on morphometric, anatomical, molecular, and geographic analyses, indicate its belonging to the putative allotetraploid C. heuffelianus of south-eastern Europe and the Balkans, and an expansion of its range to the southeast. Given the taxonomic uncertainty and unclear phylogenetic relationships of the taxa in the Crocus vernus complex, we considered it appropriate to accept our taxon as Crocus heuffelianus. So far, only C. tommasinianus Herb. has been found in Bulgarian flora from the Crocus series Verni, but in terms of altitude and morphological features, the species from our collection is close to the Balkan endemic C. veluchensis, which belongs to the C. sieberi aggregate. Morphologically, it differs by the dark, heart-shaped spots on the tip of the tepals, and the presence of one bract. A detailed comparative anatomical analysis between the three species of crocuses from the series Verni in Bulgaria shows discrete differences: the width of the white stripe and lacunar area are good distinguishing features, as are the number of conducting vessels.In the Pirin Mountains, at an elevation of around 1000 m, three populations of a new species of Bulgarian flora from the genus Crocus contains over 235 species worldwide [Crocus Mathew and Nudiscapus Mathew [Verni series, with mostly spring-flowering crocuses from central and southern Europe, some of which are important ornamentals [C. tommasinianus Herb is the only known Bulgarian flora from the series Verni. In February 2023, a large population of a species unknown to our flora, with a V-shaped to heart-shaped spot on the tips of their purple tepals, was discovered above the town of Bansko. The species was determined to be the closest in comparative morphological characters to Crocus heuffelianus Herb., which belongs to the series Verni. During field surveys in the Pirin region, distant from the first population, two more populations of the same taxon were observed. In terms of altitude, ecological conditions, and morphological features, our species is close to the Balkan endemic C. veluchensis Herb., which belongs to the C. sieberi aggregate [Crocus vernus (L.) Hill. is a European alpine species with a general distribution west to the Pyrenees and Alps, east to Ukraine, and south to Sicily and Albania [Crocus heuffelianus in the synonymy of C. vernus ssp. Vernus, and has also included C. scepusiensis (Rehm. et Wol.) Borb., C. napolitanus Mord. Laun et Lois, and C. purpureus Weston within it. [C. heuffelianus as a distinct taxon [The genus orldwide . One of ggregate ,5. Crocu Albania . Mathew ct taxon ,9,10,11.Crocus heuffelianus is distributed east to Austria, throughout the Balkan Peninsula, with the southern border in Albania [Crocus heuffelianus is closely related to several taxa with ambiguous taxonomic ranks accepted by different authors, e.g., C. scepusiensis (Rehmer & Wol.) Borb\u00e1s ex Kulcz., C. vittatus Schloss. & Vuk., nom. illeg. Crocus vernus is a European alpine species, with a general distribution in the Pyrenees and Alps, east to Ukraine, and south to Sicily and Albania [C. heuffelianus [C. heuffelianus and C. vernus. Albania . It exte Albania , with th Albania ,9,10. Cr Albania ,6. Recenfelianus testify Verni series with different geographical origins have been carried out [A good taxonomic marker in crocuses can be found in the literature at the level of leaf micromorphology ,16,17,18ried out .Verni by morphology, anatomy, karyology, and molecular genetic markers proves allopolyploidy as a result of introgression between C. heuffelianus and C. vernus. The range of C. heuffelianus s.str. is in the Carpathians, and the western Balkans have occurred only tetraploids of C. cf. heuffelianus [The phylogenetic relationships in the group are unclear. There are difficulties related to species differentiation, nomenclature, synonymy, and taxonomic affiliation ,18. A stfelianus .C. veluchensis and the closely related C. tommasinianus. On the other hand, morphological differences do not always reflect kinship relationships. For this reason, we undertook sequencing of the internal transcribed spacer region (ITS: ITS1 + 5.8S rDNA + ITS2), which has already been successfully used in phylogenetic studies in the genus Crocus [Due to taxonomic difficulties and unclear species status, a comparative morphological and anatomical study of the newly discovered taxon was made with the morphologically similar species s Crocus ,21.Crocus heuffellianus is a spring synanthous geophyte floristic region , Scila bifolia L., Ficaria verna Huds., Alchemilla sp., Achillea sp., Erythronium dens-canis, Viola sp., Sanicula europaea L., Corydalis sp., Oxalis acetosella L., Gagea reticulata Schult. & Schult. f. mosses, and grasses of Poaceae in an early phase.Three localities of c region . The pop3 and 5% . The firC. heuffelianus occurred were outside the territory of the Pirin National Park, on unprotected land. The population in Bansko was on the territory of the town, on one of the former meadows still without building activities. The other two localities were on the bank of the Desilitsa River, under slight anthropogenic pressure (namely roads and extensive tourism). The localities where C. heuffelianus from the evaluated populations are presented in The anatomical features of C. heuffelianus, C. tommasinianus, and C. veluchensis showed distinguishable bifacial profiles (Crocus (lacuna area) has a different ratio to leaf width. The ratio between the white stripe and the section width is 1/5 in C. tommasinianus and 1/4 in C. heuffelianus and C. veluchensis. The cross-sections of the leaves of profiles . The typC. heuffelianus is almost rectangular. The widest vascular bundles are concentrated on the keel base. The keel base has almost straight angles, without ribs and two at the keel (the largest). Crocus veluchensis has six larger vascular bundles: two terminal bundles, two on the bottom of the keel, and two at the blade near the lacuna area (the corner bundles). Similar is the ratio of the vascular bundles in C. tommasinianus, but not as clearly visible, and sometimes with larger bundles in the blade. According to the broadest bundles in the cross-section, C. veluchensis has the largest terminal vascular bundles, and this size is due to the larger cap of sclerenchyma. Crocus heuffelianus has the smallest terminal vascular bundles, according to the maximum size in the cross-section. The corner vascular bundle is 20% of the maximum in C. heuffelianus, as the other species have a higher value of this characteristic . The rest of the sequences are grouped in the clade of C. sieberii, which also contains C. rujanensis, C. atticus, C. dalmaticus, and C. robertianus.The phylogenetic tree follows C. heuffelianus [C. cf. heuffelianus [The morphological features of the Bulgarian specimens coincide with the morphological data for felianus , except felianus .C. heuffelianus. The quantitative differences between the tepal sizes are not discrete, but the largest tepals are those of C. heuffelianus (33\u201358 \u00d7 7\u20138 mm), followed by C. veluchensis (18\u201355 \u00d7 6\u20137 mm), and C. tommasinianus (22\u201343 \u00d7 6\u20137 mm).The corm tunics of the three species are fibrous, without detaching rings, and with unclear interweaving at the tips. The heart-shaped purple spot on the tepal tips is a key morphological feature of Verni, as well as the fact that C. veluchensis has bracteoles but no bracts. The tinted tepal tip is a constant feature in the observed populations. Despite the data for a smooth perigone throat in C. heuffelianus [C. heuffelianus have pubescent throats [C. heuffelianus and C. tommasinianus of the width of the keel. A commonly used characteristic is the width of the white stripe running axillary along the central part of the leaf as a ratio to the diameter of the leaf . This raC. heuffelianus is almost rectangular. In comparison, the keel of C. tommasinianus has two thin ribs on the bottom. The two species above have keels with a straight base. In contrast, the keel of C. veluchensis is widely arcuate, with a central vascular bundle placed in the curve. The keel angles of C. heuffelianus and C. tommasinianus are covered with papillae, which can be seen on the whole surface of the leaf, just as the keel angles of C. veluchensis look without papillae.Another important difference is the shape of the keel . The keeC. heuffelianus varies more (19\u201342) than in C. tommasinianus (20\u201325) and C. veluchensis (21\u201328). Despite the wider variation in C. heuffelianus, this parameter could not be used as a single criterion. Combined with ratios of the major vascular bundles , it could set a usable way to recognize C. heuffelianus , C. tommasinianus , and C. veluchensis . This fact demonstrates the close relationship between both taxa. According to the literature [C. heuffelianus between Ser. C. heuffelianus sensu lato in the flora of Bulgaria. Following the reason above, the members of Ser. Verni are grouped in a single branch, as are the samples of C. veluchensis. All samples of C. veluchensis from Bulgaria have almost identical ITS1/2 sequences with that of a referent specimen from Hungary. The other samples, annotated as C. veluchensis, stand in another branch. The phylogenetic tree confirmsC. heuffelianus sensu lato. The species have been neglected because of the visual similarity with C. veluchensis, and the insufficient investigations in the genus Crocus in Bulgaria.The evaluated taxon is new to the country, and is morphologically close to the description of Verni, further studies of Bulgarian representatives should be focused on karyological aspects, namely chromosome number and genome size.Given the presence of polyploidy in ser. C. heuffelianis, one of C. tommasinianus, and eight of C. veluchensis. Crocus tommasinianus is protected by Bulgarian environmental law. In this case, the plants were collected after permission from the Bulgarian Ministry of Environment and Water (authorization 871/24.04.2021). For comparative specimens, plant materials were used from the herbaria SOA and SOM , as well as high-resolution images from foreign herbaria downloaded from GBIF.org [http://openstreetmap.org (accessed on 8 November 2022).The study was based on fresh individuals collected from Bulgaria: three populations of GBIF.org ,30,31,32GBIF.org on a layC. heuffelianus, compared with fresh and dry specimens of C. tommasinianus and C. veluchensis. The metric values were measured using a calliper. The images of seeds and small parts were photographed using a stereomicroscope (Leica EZ4W). The morphological analysis was made on 30 fresh individuals of The fresh specimens collected in this study are represented below by floristic region (subregion in brackets), MGRS square, locality description, decimal coordinates (if available), altitude, date (collectors), herbarium acronym , and speCrocus heuffelianusBULGARIA: Pirin (North): 34TGM03: Bansko, 1020 m, N41.821668 E23.476085, 2023-03-06 (G. Gerdjikov) SOA 063340; 1018 m, N41.82177 E23.47616, 2023-03-16 (coll. T.Raycheva and K.Stoyanov) SOA 063342 (GenBank OQ918262); 34TGM13: Between Dobrinishte and the hut Goce Delchev, on the bank of Desilitsa River, 1000 m, N41.796684 E23.567387, 2023-03-17 (coll. Ts. Raycheva and K. Stoyanov) SOA 063351 (GenBank OQ918261); 34TGM12: Between Dobrinishte and the hut Goce Delchev, under Mogilata Peak, 1015 m, N41.78486 E23.55544, 2023-03-17 (coll. T.Raycheva and K.Stoyanov) SOA 063348 (GenBank OQ918260).Crocus veluchensisBULGARIA: Stara Planina : 35TLH03: Beklemeto Narrow, 1440 m, N42.767 E24.611, 2022-04-12 (coll. T. Raycheva and K. Stoyanov) SOA 063262;35TLH04: Beklemeto Narrow, 1270 m, N42.79673 E24.62651; 2019-04-04 (coll. N. Trifonov) SOA 062631; 35TLH53: Ispolin Peak, 1523 m, N42.7386111 E25.2522222, 2018-04-05 (coll. Y. Marinov) SOA 062486; Vitosha region: 34TFN81: above Akademika sport base, under Skoparnika Peak, 1905 m, N42.54838 E23.31165, 2018-04-21 (coll. K. Stoyanov) SOA 062475; under Trite Komini peak, 2223 m, N42.55867 E23.28389, 2019-06-10 (coll. K. Stoyanov) SOA 063121; 34TFN91: above the panoramic path, 1080 m, N42.60176 E23.3234, 2019-04-11 (coll. K. Stoyanov) SOA 062632; Pirin (North): 34TFM92: 34TFM93: Betolovoto locality, on the bank of Byala Reka, 1112 m, N41.84798 E23.39011, 2021-06-26 (coll. T. Raycheva and K. Stoyanov) SOA 063230, 2022-03-29 (coll. Ts. Raycheva and K. Stoyanov) SOA 063259; 34TFM94: Predela Narrow, 1054 m, N41.892357 E23.330803, 2023-03-17 (coll. T. Raycheva and K. Stoyanov) SOA 063350; 34TGM12: Between Dobrinishte and the hut Goce Delchev, under Mogilata Peak, 1015 m, N41.781837 E23.549747, 2023-03-17 (coll. T.Raycheva and K. Stoyanov) SOA 063356 (GenBank OQ920186); Rhodopi Mts. (West): 34TGM35: Artificial pine forest between Sveta Petka and Yundola, 1327 m, N42.046604 E23.869862, 2022-03-27 (coll. T. Raycheva and K. Stoyanov) SOA 063260; Open places over Avramovo Railway Station, 1270 m, N42.03593 E23.81844, 2023-03-16 (coll. T. Raycheva and K. Stoyanov) SOA 063341, 063343; 34TGM36. Meadows around Yundola, 1091 m, N42.0638889 E23.8475, 2022-04-22 (coll. T.Raycheva and K. Stoyanov) SOA 063228 (GenBank OQ920187); 35TKG84: Wet meadow between Ravnogor and Atolouka localities, 1354 m, N41.9578778 E24.3486111, 2020-06-19 (coll. T. Raycheva and K. Stoyanov) SOA 063208; Rhodopi Mts. : 35TKG94: Around Vurkhovrukh Hut, 1980-04-26 (coll. M. Popova) SOA 041385; 1982-04-17 (coll. M. Popova) SOA 039223, 039833; 1488 m, N41.9611667 E24.5338889, 2019-03-24 (coll. T. Raycheva) SOA 062589 (GenBank OQ920183); 35TKG95: Between Peroushtitsa and Skobelevo, 960 m, N42.0162778 E24.5505833, 2019-03-24 (coll. T. Raycheva) SOA 062584 (GenBank OQ920184); 812 m, N42.02534 E24.54629, 2019-03-24 (coll. T. Raycheva) SOA 062588; 2020-04-19 (coll. T. Raycheva) SOA 062784; 35TLG04: the road to Stoudenets, N41.96896 E24.68819, 1420 m, 2019-04-11 (coll. G. Karaycheva and T. Raycheva) SOA 062634, 062635; 35TLG05: Boykovo, in the village, N42.00169 E24.62325, 1086 m, 2018-04-01 (coll. K. Stoyanov) SOA 062482; Around the Zdravets hut, 1185 m, N42.0041667 E24.6930556, 2018-03-10 (coll. Ts. Raycheva) SOA 062485 (GenBank OQ920185); 35TLG11: Rozhen narrow, 1425 m, N41.67148 E24.72673, 2021-06-11 (coll. T. Raycheva and K. Stoyanov) SOA 063158; Momchilovtsi 2022-04-06 (coll. V. Trifonov) SOA 063257.Crocus tommasinianusBULGARIA: Forebalkan (West): 34TFP14: Darkov-Dol locality, 378 m, N43.78833 E22.41325, 2020-03-13 SOA 062847; 34TFP34: Yonov-Bair hill, 348 m, N43.76794 E22.72396, 2020-03-13 SOA 062849; 34TFP15: Vagleshtarnika locality, 377 m, N43.80896 E22.39386, 2020-02-29 SOA 062848.Quantitative measurements and observations of qualitative features of fresh samples for the morphological analyses were conducted. To examine the leaf anatomy, 10 individuals per population, from 3 populations in total, were collected during the flowering time and conserved in 75% ethanol. Transverse cross-sections and epidermal areas of leaves from each individual were manually constructed from the middle part. The epidermis was peeled using a surgical scalpel. The microscopic slides were fixed with glycerine. The snapshots of the microscope slides were taken using the Leica 750 and Motic Panthera digital microscopes, while the measurements of the characters were completed using Micam 2.4 software . The 24 The plant genomic DNA was purified as described using the DNeasy Plant Mini Kit , as described earlier . The quality of the resulting DNA was assessed spectrophotometrically, using the Epoch\u2122 Microplate Spectrophotometer, Agilent Technologies, Santa Clara, CA, USA, and DNA integrity was evaluated by 1% agarose gel electrophoresis.Crocus heuffelianus, C. veluchensis and other referent species are described in The DNA fragment encoding for the ITS1\u20135.8S rDNA\u2013ITS2 cluster was amplified using the following primers: ITS-A (5\u2032\u2013GGAAGGA-GAAGTCGTAACAAGG\u20133\u2032) and ITS-B (5\u2032\u2013CTTTTCCTCCGCTTATTGATATG\u20133\u2032) ,38. The Crocus for the outgroup. The obtained nucleotide sequences were blasted against those from the NCBI Nucleotide database ,40. The"} +{"text": "Correction to: BMC Health Services Research(2023) 23:547.10.1186/s12913-023-09349-zFollowing publication of the original article , the autThe incorrect author name is: C. P. Blauveldt.The correct author name is: C. P. Blauvelt.The author group has been updated above and the original article has been"} +{"text": "The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands.A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018\u20132019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates.P < 0.001). For cancer-related procedures, duration of hospital stay decreased . Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased .Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018\u20132019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay. During the COVID-19 pandemic, a 13.6 per cent reduction in the number of surgical procedures performed was observed in 2020. Despite great pressure on healthcare, the COVID-19 pandemic did not cause an increase in adverse surgical outcomes, and oncological surgery-related duration of hospital and ICU stay were significantly shorter. Moreover, an estimated 180 000 healthcare workers have been reported to have died from COVID-19 between January 2020 and May 20212. With these large numbers, COVID-19 has caused major disruption to regular healthcare, with serious consequences for patients both with and without COVID-19.Since the onset of the COVID-19 pandemic in December 2019, 505 million infections and 6.2 million deaths have been reported worldwide4.To meet the increased demand for COVID-19-related healthcare and ICU capacity, hospitals were forced to reduce and adjust the level of regular healthcare. For example, most health institutions adopted a crisis strategy that involved the reallocation of personnel, repurposing surgical theatres and postoperative recovery areas as ICUs, and reducing hospital attendances by postponing outpatient clinic appointments. Furthermore, temporary cancellation of cancer screening programmes was observed on a national scale5. However, the impact of the deprioritization and cancellation of elective surgical care is still relatively unknown. It has been hypothesized that, because of this strategy, surgical waiting lists have expanded, leading to more patients visiting emergency departments or presenting with an advanced stage of disease, compared with the pre-COVID-19 era. Hypothetically, this may have resulted in dismal surgical outcomes and an inferior prognosis5.Although the COVID-19 pandemic affected multiple facets of healthcare, elective planned surgery is one of the fields that witnessed the greatest curtailment by many institutions, resulting in a weekly decrease of 2.4 million elective surgical procedures globally6. Therefore, data from several Dutch surgical audits, covering different surgical specialties, were analysed to gain insights into the true impact of the pandemic on elective surgical procedures in the Netherlands in 2020. The aim of this study was to determine the impact of COVID-19 on surgical care in the Netherlands, expressed as the number of procedures performed, altered treatment plans, and surgical outcomes, during 2020.To date, limited data have been available regarding the broad consequences of COVID-19 in terms of general surgical care on a national basis8.This nationwide prospective cohort study was performed in collaboration with the Dutch Institute for Clinical Auditing (DICA), an organization that facilitates clinical auditing using a validated process of systematic analysis of the quality of careFrom August 2020, surgical audits for lung cancer surgery (Dutch Lung Cancer Audit - Surgery - DLCA-S), upper gastrointestinal cancer surgery (Dutch Upper-GI Cancer Audit - DUCA), pancreatic cancer surgery (Dutch Pancreatic Cancer Audit - DPCA), hepatobiliary surgery (Dutch Hepato Biliary Audit - DHBA), colorectal cancer surgery , hip fracture surgery (Dutch Hip Fracture Audit - DHFA), aortic aneurysm surgery , and bariatric surgery (Dutch Audit for Treatment of Obesity - DATO) were expanded with an additional COVID-19 survey. This survey focused on alterations or delays in treatment and diagnosis, and perioperative outcomes during the pandemic.All hospitals in the Netherlands performing pulmonary, upper gastrointestinal, pancreatic, hepatobiliary, colorectal, hip fracture, aneurysmal or bariatric procedures were approached to participate in the Dutch COVIDSurg II Snapshot Study. Participating hospitals provided written consent to participate. Under Dutch law, no ethical approval was required as only fully anonymized data were available for the purpose of this study.All patients who underwent pulmonary, upper gastrointestinal, pancreatic, hepatobiliary, colorectal, hip fracture, aneurysm or bariatric surgery in one of the participating hospitals were included. Patients who underwent surgery between 1 January 2018 and 31 December 2019 were included in the historical cohort, and those who underwent a surgical procedure between 1 January 2020 and 31 December 2020 were included in the study group.Appendix S1).Local investigators in each participating hospital were responsible for data collection from electronic patient records in prospectively maintained web-based audit databases , duration of ICU stay, and mortality rate, which was based on postoperative deaths within 30 or 90 days after surgery or in-hospital mortality, depending on availability of data in specific audits (Table S1 and Appendix S2). Numbers of acute and elective surgical procedures were compared with those in the historical cohort. Acute surgical procedures were defined as procedures planned within 72\u2005h of first surgical presentation.It was hypothesized that the total number of surgical procedures decreased in 2020, and that the possible expansion of surgical waiting lists might have led to increased emergency department visits, diseases at more advanced stages, and so dismal surgical outcomes. Therefore, the primary endpoints included the total number of surgical procedures performed in comparison with the mean for the historical cohort treated in 2018\u20132019, as well as the number of altered treatment plans noted during the COVID-19 pandemic. Secondary endpoints were changes in postoperative outcomes, including duration of hospital stay , readmissions to hospital within 30 days of discharge, severe complications (defined as need for reintervention or ICU admission and/or causing death (Clavien\u2013Dindo grade IIIa or higher))Altered treatment plans were defined by a difference in time to surgery appointment at the outpatient clinic and the surgical procedure ), delay to surgery perceived by the surgeon , or COVID-19-related changes in surgical approach or neoadjuvant treatment plan. Data on changes in treatment plans were collected through the additional COVID-19 survey.Table S1 and Appendix S2.Variables registered in all the included audits were demographics, such as age and sex, and presence of co-morbidities. An overview of variables that were available in only a selection of audits are outlined in 10. The interval between the two COVID-19 waves is referred to as the interim period.A COVID-19 wave was defined as a time interval with a high incidence rate of SARS-CoV-2 viral infections in the Netherlands. According to the National Institute for Public Health and the Environment, the first COVID-19 wave in this study occurred between 16 March and 24 May 2020, and the second wave between 21 September 2020 and 14 July 2021. However, because this study included only patients who underwent surgical procedures in 2020, the second COVID-19 wave was considered to have ended on 31 December 2020 in this studyDescriptive statistics were used to compare demographics, surgical details, and surgical outcomes of 2020 with mean values for 2018 and 2019. The number of procedures carried out and the surgical outcomes of 2020 were analysed separately for both COVID-19 waves and the interim period, and were compared with a historical cohort in equivalent time intervals (2018\u20132019). Analyses were performed on data from all surgical audits combined and on audit-specific data.2 test. Normally distributed variables are presented as mean (s.d.), and those with a skewed distribution as median (i.q.r.); they were analysed using Student\u2019s t test or the Mann\u2013Whitney U test depending on the distribution. Missing data up to 15 per cent were excluded from the statistical analyses. When missing data exceeded 15 per cent of the total group, the missing data were analysed as a separate group. Non-registered data were excluded from the analyses. Both missing and non-registered data are presented separately in the tables. Given the major differences between the different clinical audits, subanalyses were undertaken to assess the differences between oncological and non-oncological procedures as well as acute and elective procedures. All statistical analyses were done using R version 4.0.0 .Categorical variables are presented as numbers with percentages, and were compared using Pearson\u2019s \u03c7Fig. S1, Appendices S3 and S4). Of these 40 296 patients, 13 985 (34.7 per cent) were treated surgically in 2018, 14 157 (35.1 per cent) in 2019, and 12 154 (30.2 per cent) in 2020. Of patients treated in 2020, 2133 (17.5 per cent) had surgical treatment for lung cancer, 931 (7.7 per cent) for upper gastrointestinal cancer, 663 (5.5 per cent) for pancreatic cancer, 1215 (10.0 per cent) for hepatobiliary diseases, 1933 (15.9 per cent) for colorectal diseases, 2138 (17.6 per cent) for hip fractures, 1595 (13.1 per cent) for abdominal aneurysms, and 1543 (12.7 per cent) underwent a bariatric procedure. Of all the patients included in 2020, 5494 (45.2 per cent) underwent surgery because of a malignancy.Some 40 296 patients from eight surgical audits, covering the interval from 2018 to 2020, in 50 Dutch hospitals, were included in this study (P < 0.001), and 53.5 per cent of the patients were men (Table 1). Compared with the historical cohort, a smaller proportion of patients had a BMI above 30 kg/m2 . Of those operated on in 2020, co-morbidities were present in 45.2 per cent and 42.3 per cent had an ASA grade of III or higher . Moreover, in 2020, 75 surgically treated patients (0.6 per cent) had a confirmed COVID-19 infection. Audit-specific demographics can be found in Tables S2a\u2013h and Appendix S2.In 2020, the median age was 69 (i.q.r. 57\u201377) years, which was higher than that reported for the 2018 and 2019 cohorts (67 (55\u201376) years for both; Fig. 1a). A graphical representation of the procedures performed each week by audit is shown in Fig. S2a\u2013h.During 2020, a total of 12 154 surgical procedures were carried out in the participating hospitals, representing a decrease of 14.1 and 13.1 per cent compared with 2019 and 2018 respectively. The largest decrease in the number of procedures performed in 2020 was observed during the first and second COVID-19 waves . A decrease in the number of elective procedures was observed during the first and second COVID-19 waves , whereas the absolute number of acute procedures remained stable .Most of the procedures were done in an elective setting from 2018 to 2020. However, in 2020, a larger proportion of procedures was performed in an acute setting than in 2018 and 2019 (29.4 versus 6216 in 2018\u20132019), the proportion of oncological surgical procedures performed in 2020 was higher than in the historical cohorts . The largest decrease, in absolute numbers, in oncological procedures occurred during the interim period . Moreover, compared with oncological surgical care, a larger reduction in the number of non-oncological procedures was observed in 2020 versus the historical cohort of 2018\u20132019; there was an 18 per cent decrease in the absolute numbers (6442 procedures in 2020 versus 7855 in 2018\u20132019) and a reduced proportion of procedures . Notably, the largest differences were observed during the first (90 procedures per week in 2020 versus 161 in 2018\u20132019) and second (131 procedures per week in 2020 versus 154 in 2018\u20132019) COVID-19 waves . A graphical representation of the total number of surgical procedures performed in each audit is shown in Fig. S2a\u2013h.Although there was an 8.1 per cent decrease in the absolute number of oncological surgical procedures in 2020 compared with the combined cohort of 2018\u20132019 (5712 in 2020 P < 0.001) (Table 2). The number of delayed surgical procedures reported in the additional COVID-19 survey was 839 (9.6 per cent), and the delay was most often due to reduced hospital capacity . A delay to surgical procedures was more common for non-oncological than for oncological procedures (92 versus 8 per cent) (Table 2). For colorectal, upper gastrointestinal, and hepatobiliary procedures, the time to surgery was significantly shorter in 2020 than in the historical cohorts, whereas for pancreatic and bariatric procedures it was significantly longer (S3a\u2013h and Appendix S2).In 2020, the median time to surgery was 28 (i.q.r. 2\u2013104) days, which was shorter than the 34 (6\u2013109) days in 2019 and 36 (8\u2013120) days in 2018 , no change in the use of minimally invasive surgical techniques was noted when compared with the historical reference cohort together . In 1.7 per cent of the surgical procedures undertaken in 2020 (149 patients), a change in the surgical approach was reported in the additional COVID-19 survey. The main reason for the change was lack of capacity (96.6 per cent). Regarding neoadjuvant treatment plans, a change in the neoadjuvant treatment plan was reported for 26 patients (0.6 per cent), mainly leading to the cancellation of neoadjuvant treatment (11 of 26) (Table 2).Overall, minimally invasive techniques (such as laparoscopic or robot-assisted techniques) remained the dominant surgical approach. With regard to oncological surgical care, although it appears that a significant change in the use of minimally invasive surgical techniques was noted (61.1 per cent in 2020 versus 6 (4\u201310 days) respectively (P < 0.001) (Table 3). With regard to the different time intervals in 2020 compared with 2018\u20132019, this reduction in duration of hospital stay for oncological procedures occurred during both the COVID-19 waves and the interim period (Table 4). A significant audit-specific decrease in duration of hospital stay compared with the historical cohort was observed in one or more intervals in 2020 for patients who underwent colorectal, hepatobiliary, pulmonary, upper gastrointestinal, aneurysm, and hip fracture procedures. Audit-specific data on postoperative surgical outcomes are available in Tables S4a\u2013h and Appendix S2.Median duration of hospital stay for oncological procedures was significantly shorter during 2020 than in the historical reference group: 5 (i.q.r. 3\u20139) Table S1a,b and Appendix S2), severe complications were documented more frequently during 2020 than for the historical reference cohort . This increase in complication rate was present during both COVID-19 waves in 2020 compared with historical reference group (Table 4). However, when surgery-specific audit data were reviewed, a significant difference in severe complication rate was not observed for oncological surgical care or for any of the individual audits (Tables S4a\u2013h and Appendix S2).For the cohort for which complications, reinterventions, ICU admissions, and mortality were registered (Table 3). However, the audit-specific data showed a significantly higher rate of readmissions within 30 days for upper gastrointestinal procedures during the second COVID-19 wave (Tables S4a\u2013h and Appendix S2).For both oncological and non-oncological procedures, rates of readmission within 30 days in 2020 were similar to those in 2018\u20132019 . During the first COVID-19 wave, a higher percentage of ICU admissions was observed than in the historical reference cohort , in contrast to the second COVID-19 wave and the interim period, during which there was a lower proportion of ICU admissions (Table 4). Audit-specific ICU admission rates were also found to decrease for colorectal, pulmonary, upper gastrointestinal, and abdominal aneurysm procedures (Tables S4a\u2013h and Appendix S2). Median duration of ICU stay was shorter in 2020 than in 2018\u20132019 in the specific audits of pulmonary, upper gastrointestinal, and abdominal aneurysm procedures.During 2020, the proportion of ICU admissions decreased significantly compared with that in the historical cohort (16.5 P = 0.373). In total, 11 surgical patients (0.1 per cent) in this study cohort died after surgery because of a COVID-19 infection. Postoperative mortality rates increased during the second COVID-19 wave for the total cohort . The highest rate of COVID-19-positive mortality was observed during the second COVID-19 wave (8 patients). For patients who underwent colorectal surgery, increased audit-specific mortality rates were documented during the second COVID-19 wave .During 2020, postoperative mortality rates remained unchanged compared with those in the historical reference cohort as opposed to procedures for malignant diseases (37.7 per cent). These findings, predominantly indicating the cancellation of non-oncological elective healthcare during the first COVID-19 wave, are in line with the present results and some other recent studies, which described a decrease in procedures performed19, especially in March\u2013April 202024. One of these, a neurosurgical study23 undertaken in a large centre, also reported an increase in procedures performed in July 2020, with a decrease in operating capacity of between 30 and 55 per cent. The authors found that emergency procedures were not affected by decreased operating room capacity, which is in line with the results of the present study. Moreover, the fact that oncological surgical care seemed to be less affected by the COVID-19 pandemic is supported by the findings of Foo et al.25, who noted that, even with precautionary measures, oncological colorectal procedures were still performed according to the standard of care in three Asian hospitals. Rottoli et al.20, who looked at stage migration and worse postoperative outcomes after colorectal surgery owing to COVID-19 in 20 hospitals in northern Italy in 2020 compared to 2019, found that undergoing surgery in 2020 was not a predictor of advanced oncological stage and more surgical complications.The reduction in elective surgical care in this study is consistent with the findings of an analysis by the Global COVIDSurg Collaborative27, and a longer stay after elective orthopaedic hip surgery28. Shorter hospital stay might be explained by the endeavour of healthcare personnel to discharge patients earlier than usual, to minimize the risk of admission-related COVID-19 infections, or to achieve a higher hospital capacity because of staffing problems and fear of potentially high volumes of patients with COVID-19 being expected to arrive30. Another factor that may have influenced duration of hospital stay after hip fracture repairs could have been the institutional outflow mechanisms to rehabilitation facilities. At first, transferring patients to other healthcare facilities after surgery was more cumbersome as a result of mandatory testing policies and limited access owing to COVID-19 outbreaks in rehabilitation facilities4. However, high COVID-related mortality rates among people aged 60 years and above, and faster outflow to rehabilitation facilities or nursing homes could have led to a shorter hospital stay during later stages of the COVID-19 pandemic4. There was no evidence in the present study to suggest that more rapid discharge from hospital was associated with higher complication and readmission rates.Concerning the impact of COVID-19 on duration of postoperative hospital stay, the published literature remains ambiguous, with a shorter stay reported after hip fracture and colorectal cancer surgery31, regardless of the COVID-19 pandemic. Another limitation lies in the fact that only patients who underwent surgery in 2018\u20132020 were registered, and so conclusions could not be drawn regarding those who did not receive surgical care. Changes in surgical therapy plans for procedures that were postponed from 2020 to 2021 or surgical procedures that were cancelled because of COVID-19 were not captured here. Furthermore, because this study only included data from patients who underwent surgery up to December 2020, no assessment of long-term consequences, such as increased waiting lists or possible stage migration, was possible. Finally, for logistical reasons, inclusion for this study was started on 1 January 2020. However, the first COVID wave started later that year and the first patients would not have been affected by the pandemic. This was addressed by showing figures for the COVID waves and comparing these with historical data, not only using data for the whole year.This study has certain limitations. One limitation concerns the variability in registration of data by the different audits. Differences exist in the way variables are registered, which results in missing data for variables that were not registered in specific audits. For example, not all audits register reinterventions or ICU admissions, or use the Clavien\u2013Dindo classification for complications. Second, overall data from combined audits should always be interpreted with caution, as they cover a broad spectrum of diverse procedures with their own indications and treatment patterns. These general data and the overall trends deduced from them might not do justice to audit-specific trends that could be present. For example, no information was available about changes in planned anastomoses/stoma formation as a result of the COVID-19 pandemic. Furthermore, increased time to pancreatic surgery could, for example, be explained by alterations in neoadjuvant treatment strategies advised in guidelines32. Another possible explanation for the relatively small decline in most urgent surgical care might be the observed shortening of hospital stay, which potentially led to a higher hospital capacity as a result of a higher turnover rate.From a clinical perspective, the decrease in number of non-oncological procedures compared with the number of elective oncological and acute procedures reflects the general thought that the most urgent healthcare was prioritized and that, by postponing less urgent surgical care, capacity was preserved to maintain oncological and acute surgical careThe findings of this study suggest that the aftermath of the pandemic, reflected by increased waiting lists, will soon become apparent for patients undergoing elective non-oncological surgery. With the current shortage of ICU capacity and trained staff, the observed decrease in ICU admissions for oncological procedures may represent an important lead to reinvestigate the indications for standardized postoperative ICU admission for each procedure.Although the downscaling of healthcare was inevitable, it did not result in an increased volume of acute surgical care compared with the pre-COVID-19 era. Moreover, the decline in healthcare did not lead to dismal surgical outcomes in patients who did undergo surgery, because the duration of hospital stay and ICU admission rates decreased, and, most importantly, there was no increase in complication or mortality rates. However, from a patient perspective, the aftermath of the pandemic in terms of increased waiting lists and insecurity felt will probably become apparent in the coming years. Nonetheless, although this has been a tour de force for all healthcare workers and patients whose operations were cancelled or delayed, this study has shown the potential for even more efficient surgical care, which is greatly needed in order to catch up with all postponed surgical care.Dutch CovidSurg Collaborative Study Group: J.N. Helleman, C.L. Koningswoud-Terhoeve , E. Belt, J.A.B. van der Hoeven, G.M.H. Marres, F. Tozzi, E.M. von Meyenfeldt . R.R.J. Coebergh - van den Braak, S. Huisman, A.M. Rijken , R. Balm, F. Daams, C. Dickhoff, W.J. Eshuis, S.S. Gisbertz, H.R. Zandbergen , K.J. Hartemink, S.A. Keessen, N.F.M. Kok, K.F.D. Kuhlmann, J.W. van Sandick, A.A. Veenhof. A. Wals , Amsterdam, the Netherlands), M.S. van Diepen, L. Schoonderwoerd, C.T. Stevens , D. Susa , B.L.W. Bendermacher, N. Olofsen , M. van Himbeeck, I.H.J.T. de Hingh, H.J.B. Janssen, M.D.P. Luyer, G.A.P. Nieuwenhuijzen, M. Ramaekers, R. Stacie , A.K. Talsma, M.W. Tissink , D. Dolmans , R. Berendsen, J. Heisterkamp, W.A. Jansen, M. de Kort-van Oudheusden, R.M. Matthijsen , D.J. Gr\u00fcnhagen, S.M. Lagarde, A.P.W.M. Maat, P.C. van der Sluis, R.B. Waalboer , V. Brehm, J.P. van Brussel, M. Morak , E.D. Ponfoort, J.E.M. Sybrandy , P.L. Klemm, W. Lastdrager, H.W. Palamba , S.M. van Aalten, L.N.L. Tseng , K.E.A. van der Bogt, W.J. de Jong, J.W.A Oosterhuis, Q. Tummers, G.M. van der Wilden , S. Ooms, E.H. Pasveer, H.T.C. Veger , M.J. Molegraafb, V.B. Nieuwenhuijs, G.A. Patijn, M.E.V. van der Veldt , D. Boersma, S.T.W. van Haelst, I.D. van Koeverden, M.L. Rots , B.A. Bonsing, N. Michiels, O.D. Bijlstra, J. Braun, D. Broekhuis, H.W. Brummelaar, H.H. Hartgrink, A. Metselaar, J.S.D Mieog, I.B. Schipper, W.O. de Steur, , B. Fioole, E.C. Terlouw , C. Biesmans, J.W.A.M. Bosmans, S.A.W. Bouwense, S.H.E.M. Clermonts, M.M.E. Coolsen, B.M.E. Mees, G.W.H. Schurink , J.W. Duijff, T. van Gent, L.C.F. de Nes, D. Toonen , M.J. Beverwijk, E. van den Hoed, B. Keizers, W. Kelder, B.P.J.A Keller, B.B. Pultrum, E. van Rosum, A.G. Wijma , F. van den Broek, W.K.G. Leclercq, M.J.A. Loos, J.M.L. Sijmons, R.H.D. Vaes, P.J. Vancoillie , E.C.J. Consten, J.M.J. Jongen, P.M. Verheijen, V. van Weel , C.H.P. Arts, J. Jonker, G. Murrmann-Boonstra, J.P.E.N. Pierie, J. Swart , E.B. van Duyn, R.H. Geelkerken, R. de Groot, N.L. Moekotte, A. Stam, A. Voshaar , G.J.D. van Acker, R.M.A. Bulder, D.J. Swank , I.T.A. Pereboom , W.H. Hoffmann, M. Orsini , J.J. Blok, J.H.P. Lardenoije, M.M.P.J. Reijne, P. van Schaik, L. Smeets, S.M.M. van Sterkenburg , N.J. Harlaar, S. Mekke, T. Verhaakt , E. Cancrinus , G.W. van Lammeren, I.Q. Molenaar, H.C. van Santvoort, A.W.F. Vos , A.P. Schouten- van der Velden, K. Woensdregt , S.P. Mooy-Vermaat, D.M. Scharn , H.A. Marsman, F. Rassam , F.R. Halfwerk , A.J. Andela, C.I. Buis, G.M. van Dam, K. ten Duis, B. van Etten, L. Lases, M. Meerdink, V.E. de Meijer, B. Pranger, S. Ruiter, M. Rurenga, A. Wiersma, A.R. Wijsmuller , K.I. Albers, P.B. van den Boezem, B. Klarenbeek, B.M. van der Kolk, C.J.H.M. van Laarhoven, E. Matth\u00e9e, N. Peters, C. Rosman, A.M.A. Schroen, M.W.J. Stommel, A.F.T.M. Verhagen, R. van der Vijver, M.C. Warl\u00e9, J.H.W. de Wilt , J.W. van den Berg, T. Bloemert, G.J. de Borst, E.H. van Hattum, C.E.V.B. Hazenberg, J.A. van Herwaarden, R. van Hillegerberg, T.E. Kroese, B.J. Petri, R.J. Toorop , F. Aarts, R.J.L. Janssen, S.H.P. Janssen-Maessen, M. Kool, H. Verberght , D.E. Moes, J.W. Smit, A.M. Wiersema, Westfriesgasthuis / Dijklander hospital, Hoorn, the Netherlands), B.P. Vierhout, B. de Vos , F.C. den Boer, N.A.M. Dekker , J.M.J. Botman, M.J. van Det, E.C. Folbert, E. de Jong, J.C. Koenen, E.A. Kouwenhoven, I. Masselink, L.H. Navis , H.J. Belgers, M.N. Sosef, J.H.M.B. Stoot .Appendix S4 and S5.Dutch CovidSurg Collaborative study group: see znac301_Supplementary_DataClick here for additional data file."} +{"text": "Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases.Here, we investigated the epidemiological, clinical, and mycological features of candidemia in Tehran, Iran.Candida isolates were molecularly identified by sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). The antifungal susceptibility testing for fluconazole,itraconazole, voriconazole, posaconazole, amphotericin B, caspofungin, micafungin, and anidulafungin against the isolates was performed using CLSI broth microdilution reference method (M27-A3). A prospective observational study of all patients diagnosed with candidemia was performed at two referral teaching hospitals in Tehran, Iran, from February to December 2018.Demographic characteristics, underlying diseases, risk factors, clinical symptoms, and laboratory analyses of candidemic patients with positive culturewere mined. C. albicans (44%) was the most frequent causative agent, followed by C. glabrata (21%), C. parapsilosis complex(15%), C. tropicalis (11%), and C. lusitaniae (3.5%). All the isolates were susceptible to amphotericin B. The activity of all four azoles waslow against non-albicans Candida species, especially C. tropicalis. A total of 89 episodes were identified, with an incidence of 2.1 episodes/1000 admissions. The common underling disease were malignancy (46%), renal failure/dialysis (44%), and hypertension (40%).The overall crude mortality was 47%. albicans Candida species with reduced susceptibility to antifungal drugs might be alarming in high-risk patients.Therefore, accurate knowledge of predisposing factors and epidemiological patterns in candidemia are effective steps for managing and decreasing the mortality rate in candidemia. The increase in non- Candida species remain the most commonly encountered pathogens isolated from bloodstream infections (BSIs) globally and are associated with significant morbidity and mortality, particularly among hospitalized patients receiving immune-suppressive therapy or diagnosed with a serious underlying health condition were more frequently isolated from ICU. Based on Candida species, fever and cough were moreprevalent in C. albicans infections, while diarrhea was more prevalent in C. glabrata and C. parapsilosis complex ,and pleural effusion was more observed in C. parapsilosis infections . The most common underlying disease in C. glabrata, C. parapsilosis complex,and C. tropicalis infections were renal failure/dialysis , malignancy and sepsis , as well as malignancy , respectively.CVC was the most common risk factor of candidemia due to C. albicans , C. glabrata , C. parapsilosis ,and C. tropicalis .C. albicans andNAC species. This analysis revealed that malignancy was an independent risk factor for candidemia (P=0.013).In the study, 89 C. albicans and C. glabrata ,but lower in patients with C. parapsilosis than other species. In the multivariate analyses of risk factors for BSIs mortality, intubation (P=0.001) and urinary catheterization (P=0.03)were independent risk factors for mortality received antifungal therapy. Initial treatment was with fluconazole in 33 patients ,caspofungin in 29 patients , liposomal amphotericin B in 22 patients , and 14 patients received other antifungal agents . Meanwhiortality .50, MIC90, geometric means (GM) MIC, and MIC modes of eight antifungal drugs against 89 Candida isolatesrecovered from candidemic patients. In terms of MIC50 and MIC90, echinocandins demonstrated the highest MIC against C. parapsilosis which was higher than other NAC species. However, we did not detect resistance toechinocandins in any of the C. tropicalis, C. guilliermondii, C. lusitaniae, C. krusei,and C. kefyr isolates. Among common species, C. albicans showed highsusceptibilities to fluconazole (97.4%), while fluconazole susceptibility was lower in NAC species, particularly in C. tropicalis (S=40%). C. glabrata exhibited the highest MIC50 for fluconazole (16\u03bcg/ml). The activity of all four azoles was low against\u00a0NAC species;however, C. albicans has a lower MIC50 and MIC90 for fluconazole, itraconazole, voriconazole, and posaconazole, respectively.Accordingly, C. albicans was the most prevalent of the candidemia episodes (43.8%).Among the NAC species, C. glabrata was the predominant species, followed by C. parapsilosis, C. tropicalis,and C. lusitaniae. In most previous studies across the world, C. albicans was the most common species isolated from candidemia,which is consistent with the results of our study [ C. parapsilosis (30.8%) was the leading agent of candidemia in Iran [ C. glabrata is the most common NAC species in this study [ C. parapsilosis has been the most prevalent NAC species [ C. glabrata BSI. However, the increasing reports on refractory BSI caused by fluconazole and echinocandins resistant C. glabrata isolates are alarming.It has been shown that C. lusitaniae can rapidly acquire multidrug resistance traits (MDR) during the course of antifungal treatment with fluconazole, amphotericin B,and caspofungin [ C. kefyr can cause serious infection in patients with hematologic malignancies and recently has shown resistance to amphotericin B [ C. norvegensis is also shown to be azole-resistant [ C. albicans species were resistant to fluconazole.Our study confirmed that primary fluconazole resistance is uncommon in C. albicans. The majority of C. albicans are sensitive to amphotericin B, fluconazole,itraconazole, voriconazole, posaconazole, and echinocandins in vitro, especially in patients without a history of exposure to antifungal agents [ C. albicans, C. tropicalis, and C. parapsilosis [ C. tropicalis has been previously reported as 5.0%\u20137.2% from two reports from the ARTEMIS study over 12 years [ C. tropicalis in this study was similar to other studies from Asia [ C. tropicalis isolates in our study, six were resistant to voriconazole. Many candidemia studies revealed a significant increasein azole-resistant C. tropicalis blood isolates and some reported pan-azole and amphotericin B-resistant isolates [ C. tropicalis and C. auris isolates also carry the MDR traits [ C. glabrata isolate is defined as fluconazole MIC \u2264 32 mg/l since 2012. Overall, 94.7% of C. glabrata isolates werecategorized as SDD that is consistent with the findings of studies from the Asian-Pacific region [ C. guilliermondii, C. lusitaniae, C. kefyr,\u00a0and\u00a0C. krusei (except for the intrinsic fluconazole resistance in\u00a0C. krusei). Furthermore, resistance to echinocandins was very low,except for C. parapsilosis, which exhibited higher MICs than those of other Candida species. We focused on candidemia patients and found that r study . Despitin Iran . Similas study - 26. Hspecies - 30. Mofungin . C. kefricin B . C. norsistant . While agents . A recesilosis . The oc2 years , 37. Tom Asia , 39. Msolates . An ext traits . The su region . As demCandida isolates were identified using the DNA sequencing method to assess the exact epidemiological pattern of species distribution.The mean age of the patients in this study was 49.6 years. Most of these patients were over 40years old (68.5%). The mean age in other studies varies from 40 to 65 years.Candidemia patients mostly are admitted to ICUs. The overall crude mortality of 47.2% in our study is similar to that reported by other investigators from Iran [ et al. [ C. albicans and NAC species showed that malignancy was an independent risk factor for candidemia (P=0.013).In the multivariate analyses of risk factors for BSIs mortality, intubation (P=0.001) and urinary catheterization (P=0.03) were independent risk factors for mortality.In a prospective study performed in the ICU of a tertiary care hospital in Athens, the authors noted that the administration of glucocorticoids, presence of CVCs,and candiduria were independent risk factors for candidemia caused by NAC species [ The increased frequency of NAC may also be attributable to the improved diagnostic technique, allowing NAC species to be characterized with methods that are more sensitive.In this study, all om Iran - 45 bu et al. .Totally et al. , China species . Althouspecies , no sigCandida species in patients with candidemia in Tehran, the capital of Iran, for which there is a paucity of data regarding the epidemiology, risk factors, and antifungal susceptibility patterns of these species. Accurate knowledge of predisposing factors and epidemiological patterns can be an effective step in disease management.In this study, C. albicans is reported to be the most common species causing candidemia; however, an increasing frequency of NAC species could pose a serious therapeuticchallenge due to different antifungal susceptibility patterns. This report shows that candidemia is a significant source of morbidity in Tehran.Candidemia with a shift in species distribution towards NAC species remains a lethal disease. The results of this study provide important information regarding thedistribution of Ethical approvalBefore the collection of samples, the Ethics Committee of Tehran University of Medical Science, Tehran, Iran (IR.TUMS.SPH.REC.1396.4195) approved the procedures to be used in this study. In addition, in line with the principles of research ethics, written informed consent was obtained from individual patients.The authors express their gratitude to their colleagues, Mohammad Reza Safari and Mahsa Domanlo, for their assistance in conducting this study.S.KH., M.K., S.J.H., and M.R.S. designed the study. Material preparation, data collection, and analysis were performed by S.K.H., M.K., S.R., K.A., M.A., SH.M., A.M., M.M., N.P., K.A., N.A., and SH.S.H. The first draft of the manuscript was written by M.K., A.A., L.A.F, and S.R., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors have no conflicts of interest to declare that are relevant to the content of this article.This study has been funded and supported by Tehran University of Medical Sciences, Tehran, Iran (Grant no. 99-2-99-48944)."} +{"text": "Iris maackii (Iridaceae) has been considered a synonym of I. laevigata, a synonym of I. pseudacorus, or an accepted species. The current concept of I. maackii in the literature and databases is often applied to yellow-flowered plants with prominently veined rosette leaves, which are diagnostic features of I. pseudacorus growing in Northeast Asia. Therefore, the objective was to clarify the taxonomic identity of I. maackii. This study is based on a critical examination of the literature, on the observed morphological characters in the holotype of I. maackii, and on a morphological comparison of I. maackii with living plants of I. laevigata and I. pseudacorus. Additionally, a morphometric comparison of the seed characters was carried out to clarify the morphological distinction among I. maackii, I. laevigata, and I. pseudacorus. A careful study demonstrated that the rosette leaf texture and the morphology of the flowering stem, fruit, and seeds of I. maackii are identical to or within the variation range of I. laevigata. Thus, I. maackii is morphologically non-distinct from I. laevigata and should be recognized as a taxonomic synonym of the latter. An image of the holotype of I. maackii is provided along with detailed illustrations of I. laevigata and I. pseudacorus.Since the early 20th century, Iris pseudacorus L. However, Carl Johann Maximowicz described I. maackii Maxim. on the basis of Maack\u2019s specimen s.n. Herb. C.F. Ledebour (LE01010777!).\u2014http://rr.herbariumle.ru/01010777 (accessed on 13 August 2023).Alexeeva (p. 417)Iris maackii Maxim., Bull. Acad. Imp. Sci. Saint-P\u00e9tersbourg 26(3): 541, 1880.\u2014Holotype: (note handwritten by E. Regel): Iris Pseud-Acorus L. teste Rgl. Legit Maack; (note handwritten by C.J. Maximowicz): Iris maackii Maxim. Gegen\u00fcber d. [der] Ima M\u00fcndung linkes Ussuri uter, [fr.], (15 (27) July 1859); (note handwritten by V.L. Komarov): \u0423\u0441\u0441\u0443\u0440\u0438, \u043b\u0435\u0432\u044b\u0439 \u0431\u0435\u0440\u0435\u0433 \u043f\u0440o\u0442\u0438\u0432 \u0443\u0441\u0442\u044c\u044f \u0418\u043c\u0430\u043d\u0430 (LE01010783!).\u2014=Iris pseudacorus auct. non L. [=. non L. ,60.Iris pseudacorus L., Sp. Pl. 1: 38, 1753.\u2014\u201cI. pseudacorus var. mandshurica L.H.Bailey\u201d, Man. Cult. Pl., ed. 2: 273, 1949, nom. inval. (Art. 38.1 of the ICN).\u2014Lectotype .\u2014https://www.linnean-online.org/805/ (accessed on 13 August 2023).y Crespo (p. 56))Iris maackii auct. non Maxim. [=n Maxim. ,73,74,75Iris maackii (Iridaceae) has been unclear, and there have been various speculations as to whether it is an independent species or not. Currently, in most databases, it is regarded as a distinct species native to northeastern China and the Russian Far East [I. maackii based on a morphological study. In addition, an overview of the taxonomic history of I. maackii, based on numerous publications of scientists from 1861 to the present time, was conducted to establish its true identity. Since I. maackii is known on the basis of a single specimen indicated in the literature a,44 aI. me (e.g., ,37,38,39"} +{"text": "Miscarriage is an important problem in human reproduction, affecting 10\u201315 % of clinically recognized pregnancies. The cases of embryonic death can be divided into missed abortion (MA), for which the ultrasound sign of the embryo death is the absence of cardiac activity, and anembryonic pregnancy (AP) without an embryo in the gestational sac. The aim of this study was to compare the frequency of chromosomal abnormalities in extraembryonic tissues detected by conventional cytogenetic analysis of spontaneous abortions depending on the presence or absence of an embryo. This is a retrospective study of 1551 spontaneous abortions analyzed using GTG-banding from 1990 to 2022 (266 cases of AP and 1285 cases of MA). A comparative analysis of the frequency of chromosomal abnormalities and the distribution of karyotype frequencies depending on the presence of an embryo in the gestational sac was carried out. Statistical analysis was performed using a chi-square test with a p <0.05 significance level. The total frequency of chromosomal abnormalities in the study was 53.6 % (832/1551). The proportion of abnormal karyotypes in the AP and MA groups did not differ significantly and amounted to 57.1 % (152/266) and 52.9 % (680/1285) for AP and MA, respectively (p = 0.209). Sex chromosome aneuploidies and triploidies were significantly less common in the AP group than in the MA group (2.3 % (6/266) vs 6.8 % (88/1285), p = 0.005 and 4.9 % (13/266) vs 8.9 % (114/1285), p = 0.031, respectively). Tetraploidies were registered more frequently in AP compared to MA (12.4 % (33/266) vs. 8.2 % (106/1285), p = 0.031). The sex ratio among abortions with a normal karyotype was 0.54 and 0.74 for AP and MA, respectively. Thus, although the frequencies of some types of chromosomal pathology differ between AP and MA, the total frequency of chromosomal abnormalities in AP is not increased compared to MA, which indicates the need to search for the causes of AP at other levels of the genome organization, including microstructural chromosomal rearrangements, monogenic mutations, imprinting disorders, and epigenetic abnormalities. Miscarriage is one of the most common issues in humanreproduction that results in embryonic or fetal death in 10 to15 % of all clinically recognized pregnancies . Cytogenetic studies reveal chromosomal abnormalitiesin 50\u201360 % of first trimester abortions , and in recent years, therehas been an increasing amount of data about the associationof miscarriage with copy number variations (CNV), genemutations, methylation abnormalities and other epigeneticaberrations . Identification of embryo death causes isnecessary to assess the miscarriage risk in subsequent pregnancies;in addition, uncovering a pathogenic factor is importantfor psychological condition of the couples.Anembryonic pregnancy is the absence of an embryo in thegestational sac, and it is one of the earliest forms of miscarriage.In anembryonic pregnancy, a blastocyst is implanted intothe uterine wall, a gestational sac is formed, but the embryoitself either does not develop initially, or its formation arrestsat the earliest stages (no later than the 5th week of gestation),and then only extra-embryonic components of the conceptuscontinue to proliferate and grow.As a rule, at around 6 weeks of gestation, the secondaryyolk sac and the primary germ layers could be detected withinthe gestational sac by transvaginal ultrasound, and primitivecardiac tube could be detected during the 7th week. In earlypregnancy loss there are several ultrasonography features: theabsence of embryonic cardiac activity with a diameter of thegestational sac \u226525 mm, crown\u2013rump length (CRL) \u22657 mmfor a period of 6 weeks or more; the absence of an embryoand its cardiac activity 14 days after the detection of a gestationalsac without a yolk sac; the absence of an embryo andits cardiac activity 11 days after the detection of a gestationalsac with a yolk sac . Thus, ultrasoundscanning makes it possible to differentiate two forms of earlyembryonic death: anembryonic pregnancy (AP) and missedabortion (MA). AP is diagnosed in the absence of an embryoand a secondary yolk sac in the cavity of the gestational sac,for a period of more than 7 weeks ; inaddition, ultrasound criteria for AP are a gestational sac morethan 13 mm without a yolk sac or more than 18 mm withoutan embryo. The absence of cardiac activity in the presence ofan embryo is a sign of \u041c\u0410There are terminological inconsistencies, which make itdifficult to compare the results of studies implemented in differentcenters. The ICD-10 uses the terms \u2018blighted ovum\u2019 and\u2018missed abortion\u2019, accepted many years ago ,which do not quite represent the clinical features found usingthe ultrasound examination . TheEuropean Society of Human Reproduction and Embryology(ESHRE) special group has proposed the terms \u2018anembryonic(empty sac) miscarriage\u2019 for a gestational sac \u22658 mm in diameterand without a yolk sac or embryo; \u2018yolk sac miscarriage\u2019for a gestational sac with a yolk sac, but without an embryo;\u2018embryonic miscarriage\u2019 with an embryonic CRL of at least7 mm without cardiac activity . Thus,the diagnosis of AP includes both an empty gestational sac(empty sac) and a gestational sac with a yolk sac and withoutan embryo (yolk sac only).The estimated frequency of AP among the first trimesterpregnancy losses differs: from 16 % in early studies , 22.6 % after IVF , and up to 30\u201340 %in most studies . Despite the prevalence ofAP, data on the frequency of chromosomal abnormalities inthis pathology are contradictory. Intuitively, it seems that suchearly and pronounced violations, which lead to the developmentalarrest of the embryo per se at the initial stages of itsformation, should be associated with a significantly increasedfrequency and severity of chromosomal abnormalities. In somestudies such association was found .At the same time, most recent studies demonstrate either theabsence of significant differences in the frequency of chromosomalabnormalities between the AP and MA groups , or even a lower frequency of abnormal karyotypesin AP compared to MA .Therefore, we consider it of current interest to study largesamples of AP and MA cases in comparison with the publisheddata. In this work, we studied the frequency and spectrum ofchromosomal anomalies detected by cytogenetic analysis of1551 cases of early miscarriage, depending on the presenceor absence of an embryo.The object of this study was 1551 spontaneous abortions,karyotyped in the Cytogenetic Laboratory of the ResearchInstitute of Medical Genetics of the Tomsk National ResearchMedical Center. Products of conception (POC) were obtainedfrom gynecological clinics of Tomsk and Seversk, along withinformation regarding the patient\u2019s age, woman\u2019s obstetric and gynecological history, and the number and outcomes ofher previous pregnancies. The study was approved by theBiomedicalEthics Committee of the Research Institute ofMedical Genetics of the Tomsk National Research MedicalCenter, Protocol 10, Feb. 15, 2021. Informed consents wereobtained from all patients.In most cases, abortion karyotypes were established usingconventional GTG banding after long-term extra-embryonicfibroblast culture or direct preparationsof the chorionic villi . Conventional comparativegenomic hybridization (CGH) and interphase fluorescence in situ hybridization (FISH) withcentromere-enumeration probes were performedin cases where traditional cytogenetic analysis failed.AP were diagnosed by ultrasound examination and included266 (17.2 %) abortions . The other 1285 abortions (82.8 %) with anembryo were assigned to the MA group (where an embryonicpole was identified without cardiac activity).The POC material, usually represented by the fragments ofthe gestational sac, was delivered to the laboratory in sterilesaline, thoroughly washed from blood, and separated fromdecidual tissues. Methods of embryonic cells culture, chromosomepreparations, cytogenetic techniques, FISH and CGHwere performed as described previously .The calculation of the statistical significance of differencesbetween frequencies was performed using the \u03c72 analyses;the normality of the distribution for quantitative indicatorswas checked using the Kolmogorov\u2013Smirnov test; due tothe differences from the normal distribution, comparisonsbetween groups were performed using the nonparametricMann\u2013Whitney test. A significance level of p < 0.05 wasapplied for all tests. The sex ratio (SR) was calculated asthe ratio of karyotypes 46,XY : 46,XX. Recurrent pregnancyloss (RPL) was defined as two or more consecutive miscarriagesin a woman\u2019s obstetric history.The study was performed at the Core Medical GenomicsFacility of the Tomsk National Research Medical Center(NRMC) of the Russian Academy of Sciences using theresourcesof the bio-collection \u201cBiobank of the populationof Northern Eurasia\u201d of the Research Institute of MedicalGenetics, Tomsk NRMC.Table 1 shows the comparison of the demographic characteristicsof the studied groups of abortions. The age of mothersand fathers, the number of woman\u2019s pregnancies and spontaneousabortions, and the proportion of couples with RPL ina woman\u2019s history did not differ significantly in the samples.However, the gestational age in the AP groupwas significantly less than in the MA group.In total, abnormal karyotypes were found in 53.6 % (832/1551) of abortions. Table 2 shows the karyotype frequencies.The rates of the different types of chromosomal abnormalitiesamong pregnancy losses with and without an embryo were52.9 % (680/1285) and 57.1 % (152/266) respectively, anddid not differ significantly ( p = 0.209). We found similarfrequencies of chromosomal abnormalities between AP andMA in the autosomal trisomies (27.8 and 22.5 %), autosomalmonosomies (1.5 and 0.6 %), structural aberrations (2.3 and1.0 %) and combined anomalies that include combinations ofdifferent types of chromosomal aberrations in one abortion(4.9 and 4.2 %) (see Table 2). At the same time, numericalabnormalities of sex chromosomes in AP were three timesless common than in MA . This differencewas even more pronounced for monosomy X: 0.8 %(2/266) and 5.0 % (64/1285), p < 0.001.Triploidies occurred significantly less frequently, and tetraploidiesoccurred significantly more frequently in abortionswithout embryo in comparison with embryonic miscarriages . Since some of the tetraploid karyotypes inmosaic form may represent cultural artifacts, we reexaminedsome tetraploid samples using FISH in non-cultured tissues.The frequency of FISH-confirmed tetraploidies showed evenmore statistically significant differences: 14/266 (5.3 %) at APvs 22/1285 (1.7 %) in MA ( p < 0.001).Among the abortions with normal karyotype, the SR was0.54 for AP and 0.74 for MA; there were no significant differencesin the distribution of 46,XX and 46,XY karyotypes(p = 0.142).The aim of this study was to compare the frequency of chromosomalabnormalities in pregnancy losses with and withoutan embryo (MA and AP). In this study, we analyzed a largesample of miscarriages (1551 abortions) and did not findsignificant differences in the chromosomal abnormality ratesbetween the AP and MA groups . An analysis of previously published comparativestudies showed conflicting results regarding the correlationbetween the karyotype and the presence of an embryo in thegestational sac (Table 3).The presence of a yolk sac in a gestational sac without anembryo means that the disorders appear after the segregationof the hypoblast and epiblast, which occurs 6\u20137 days afterfertilization. The hypoblast, which gives rise to the endodermof the yolk sac, continues to develop, while the epiblast, which gives rise to the three germ layers of the embryo itself, is blocked. An emptygestational sac means that the abnormalities appeared beforethe separation of the inner cell mass into hypoblast and epiblast,i. e. during implantation . At such anearly stage, the influence of non-genetic factors is unlikely tobe significant. The lower frequency of chromosomal abnormalitiesin such embryos may be due to the fact that at suchearly stages of development, damage of the activity of genesimportant in early embryogenesis due to point mutations,CNV, or epigenetic anomalies is more critical than a changein the gene dosage due to aneuploidy.Considering the predominant contribution of genetic causes to a veryearly arrest of embryonic development, the lower frequencyof chromosomal abnormalities in the absence of an embryoin the gestational sac makes it promising to search for geneticaberrations of the sub-chromosomal level and epigeneticanomalies in AP cases . Thus, chromosomalmicroarray analysis revealed a greater number ofCNV in AP compared to MA , andin AP among pathogenic rearrangements 54.3 % deletionsand 45.7 % duplications were found, whereas in MA onlyduplications were found . Interestingly,the set of genes in CNV also differed: in AP, the genesresponsible for basic biological processes, such as migration,cell contacts, and adhesion, were more often affected, while inMA, the genes responsible for morphogenesis were affected.We found different frequencies of some types of chromosomalabnormalities between abortions with and without anembryo. In our sample, sex chromosome aneuploidies were less common in AP than in MA (seeTable 2). Frequency of the 45,X karyotype has been found tobe significantly higher in miscarriages with an embryo in mostpublished comparative studies . These results indicate that monosomy X does not have a noticeable negative effect on the early development of theembryo per se, and such embryos die at later stages, possiblydue to a failure of trophoblast function .Triploidy is another type of chromosomal abnormality,which is more common in embryonic miscarriages than inanembryonic ones. Previous studies suggested that the majorityof triploidies are the result of fertilization errors leadingto either diandry or digyny . Due to the phenomenon of chromosomal imprinting,paternal chromosomes contribute to the preferential proliferationof trophoblast tissues. Perhaps it is diandric triploidythat leads to the AP phenotype, but this assumption needs tobe verified.Common feature for both of the above mentioned types ofchromosomal abnormalities is that the mechanism of theirorigin is not associated with meiotic nondisjunction in oocytes.It is known that cases of X-chromosome monosomy are mostoften caused by errors in paternal meiosis , and triploidies are caused mostlyby fertilization errors. Therefore, the rate of these types ofkaryotype abnormalities is increased among abortions fromyoung mothers in comparison with older mothers . Since the mother\u2019sage was similar in our AP and MA samples, the higher rateof monosomy X and triploidy in MA in comparison with APsupports the assumption that embryos with these karyotypeabnormalities survive better.We found a higher frequency of tetraploidy in the AP group,which is consistent with the data of and implies an unfavorable influenceof the tetraploid karyotype, leading to an earlier terminationof embryo development.We found that sex ratio (SR) in abortions with normalkaryotype deviates from the expected SR and constitutes0.74 for MA and 0.54 for AP. Although the differencesbetween the groups did not reach a statistically significantlevel ( p = 0.142), they are consistent with the data obtainedearlier in our laboratory using significantly smaller samples.In the study it was shown that theproportion of 46,XY embryos inversely correlates with theseverity of developmentaldisorders: the SR was 0.77 forspontaneous abortions without significant intrauterine delayof development; 0.60 for MA and 0.31 for AP (compared to1.10 for control group of induced abortion). One of the reasonsfor the biased SR may be maternal cell contamination (MCC)of extra-embryonic cell cultures. But since both AP and MAsamples were analyzed concomitantly, and the frequency ofMCC was low , this equalizesthe possibleeffect of maternal contamination on SR in our study.Interestingly, a large-scale study of SR in early human development(from conception to birth) showed that SR decreasesin the first week after conception and then increases for at least 10\u201315 weeks . Thus, the excess offemale embryo loss in the first trimester of pregnancy probablyrepresents a real phenomenon.The development of cell-based technologies offers a uniqueopportunity to study the biological mechanisms that lead toembryogenesis failure. Thus, induced pluripotent stem cells(iPSCs) reproduce the characteristics of embryonic stem cells,including unlimited proliferative capacity and the ability to differentiateinto derivatives of three germ layers (pluripotency).It has been shown that iPSCs can be derived from trophoblasttissues not only from embryos with a normal karyotype, butalso from embryos with some chromosomal aneuploidies . If it is possible to reprogram trophoblastcells and obtain iPSC lines from anembryonic cases, this willopen up the possibility to study the processes in the derivativesof various germ layers leading to an early developmentalarrest of the embryo.We found that the pattern of chromosomal abnormalities partlydiffers between AP and MA, and the presence of an embryois positively correlated with sex chromosome aneuploidy andtriploidy, while the absence of an embryo is positively correlatedwith tetraploidy. At the same time, the total frequencyof chromosomal abnormalities in AP and MA did not differ,which indicates the need to search for the causes of AP atother levels of genome organization, including microstructuralchromosomal rearrangements, monogenic mutations, imprintingdisorders, and other aberrant epigenetic modifications ofthe genome.The authors declare no conflict of interest.Ahern D.T., Bansal P., Faustino I., Kondaveeti Y., Glatt-Deeley H.R.,Banda E.C., Pinter S.F. Monosomy X in isogenic human iPSCderivedtrophoblast model impacts expression modules preservedin human placenta. Proc. Natl. Acad. Sci. USA. 2022;119(40):e2211073119. DOI 10.1073/pnas.2211073119.Angiolucci M., Murru R., Melis G., Carcassi C., Mais V. Associationbetween different morphological types and abnormal karyotypes inearly pregnancy loss. Ultrasound Obstet. Gynecol. 2011;37(2):219-225. DOI 10.1002/uog.7681.Boss A.L., Chamley L.W., James J.L. 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Steril. 2005;83(4):964-972. DOI 10.1016/j.fertnstert.2004.12.009.Orzack S.H., Stubblefield J.W., Akmaev V.R., Colls P., Munn\u00e9 S.,Scholl T., Steinsaltz D., Zuckerman J.E. The human sex ratio fromconception to birth. Proc. Natl. Acad. Sci. USA. 2015;112(16):E2102-E2111. DOI 10.1073/pnas.1416546112.Ouyang Y., Tan Y., Yi Y., Gong F., Lin G., Li X., Lu G. Correlationbetween chromosomal distribution and embryonic findings on ultrasoundin early pregnancy loss after IVF-embryo transfer. Hum. Reprod.2016;31(10):2212-2218. DOI 10.1093/humrep/dew201Ozawa N., Ogawa K., Sasaki A., Mitsui M., Wada S., Sago H. Maternalage, history of miscarriage, and embryonic/fetal size are associatedwith cytogenetic results of spontaneous early miscarriages. J. Assist.Reprod. Genet. 2019;36(4):749-757. DOI 10.1007/s10815-019-01415-y.Parveen S., Panicker M.M., Gupta P.K. Generation of an induced pluripotentstem cell line from chorionic villi of a Turner syndromespontaneous abortion. Stem Cell Res. 2017;19:12-16. DOI 10.1016/j.scr.2016.12.016.Radzinsky V.E., Makletsova S.A., Aleev I.A., Rudneva O.D., RyabinkinaT.S. Missed miscarriage. Guidelines by MARS ReproductiveHealth Professional Medical Association. Moscow: StatusPraesensEditorial Office, 2015. (in Russian)Robinson H.P. The diagnosis of early pregnancy failure by sonar.Br. J. Obstet. Gynaecol. 1975;82(11):849-857. DOI 10.1111/j.1471-0528.1975.tb00588.x.Romanova O.A. Endometrium immunoreactivity in missed miscarriageassociated with chromosome aberrations in the chorion. Cand. Med.Sci. Diss. St. Petersburg, 2022. (in Russian)Savchenko R.R., Kashevarova A.A., Skryabin N.A., Zhigalina D.I.,Lopatkina M.E., Nikitina T.V., Vasiliev S.A., Lebedev I.N. Analysisof CNVs in anembryonic pregnancy and missed abortions. MeditsinskayaGenetika = Medical Genetics. 2018;17(3):49-54. DOI10.25557/2073-7998.2018.03.49-54. (in Russian)Segawa T., Kuroda T., Kato K., Kuroda M., Omi K., Miyauchi O.,Watanabe Y., Okubo T., Osada H., Teramoto S. Cytogenetic analysisof the retained products of conception after missed abortion followingblastocyst transfer: a retrospective, large-scale, single-centrestudy. Reprod. Biomed. Online. 2017;34(2):203-210. DOI 10.1016/j.rbmo.2016.11.005Soler A., Morales C., Mademont-Soler I., Margarit E., Borrell A., BorobioV., Mu\u00f1oz M., S\u00e1nchez A. Overview of chromosome abnormalitiesin first trimester miscarriages: a series of 1,011 consecutivechorionic villi sample karyotypes. Cytogenet. Genome Res. 2017;152(2):81-89. DOI 10.1159/000477707Thaker H.M. The partly molar pregnancy that is not a partial mole.Pediatr. Dev. Pathol. 2005;8(2):146-147. DOI 10.1007/s10024-005-2164-3.van den Berg M.M., van Maarle M.C., van Wely M., Goddijn M. Geneticsof early miscarriage. Biochim. Biophys. Acta. 2012;1822(12):1951-1959. DOI 10.1016/j.bbadis.2012.07.001.Veropotvelyan N.P., Kodunov L.O. The features ratio of chromosomalabnormalities and terms of persistence of gestational sacs amongundevelopingpregnancies in cases without embryo (anembrioniya)and with the existing embryo: analysis of 1328 cases. Zdorov\u2019eZhenshchiny = Health of Woman. 2015;5(101):74-80. DOI 10.15574/HW.2015.101.74. (in Russian)Wang H., Yuan D., Wang S., Luo L., Zhang Y., Ye J., Zhu K. Cytogeneticand genetic investigation of miscarriage cases in Eastern China.J. Matern. Fetal. Neonatal. Med. 2020;33(20):3385-3390. DOI10.1080/14767058.2019.1572738.Wu X., Su L., Xie X., He D., Chen X., Wang M., Wang L., Zheng L.,Xu L. Comprehensive analysis of early pregnancy loss based oncytogenetic findings from a tertiary referral center. Mol. Cytogenet.2021;14(1):56. DOI 10.1186/s13039-021-00577-8.Yoneda S., Shiozaki A., Yoneda N., Sameshima A., Ito M., Shima T., NakashimaA., Yoshino O., Kigawa M., Takamori R., Shinagawa Y., SaitoS. A yolk sac larger than 5 mm suggests an abnormal fetal karyotype,whereas an absent embryo indicates a normal fetal karyotype.J. Ultrasound Med. 2018;37(5):1233-1241. DOI 10.1002/jum.14467"} +{"text": "Arcobacter butzleri, Listeria monocytogenes, Staphylococcus aureus, and Campylobacterjejuni are significant foodborne pathogens regarding the consumption of raw poultry meat. An existing survey was conducted to assess the occurrence of S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in raw poultry meat samples.Staphylococcus aureus, C. jejuni, A. butzleri, and L. monocytogenes isolates were confirmed by standard biochemical techniques.Ninety-four raw ostrich, turkey, chicken, and quail meat samples were collected and subjected to culture-based analysis. A. butzleri, C. jejuni, L. monocytogenes, and S. aureus in poultry meat samples was 11.45%, 17.70%, 1.04%, and 16.66%, respectively. L. monocytogenes was absent in chicken, turkey, and ostrich meat samples. Only one quail meat (4.16%) was positive for L. monocytogenes. The uppermost contamination rate with A. butzleri, C. jejuni, and S. aureus was found in chicken (25%), turkey (25%), and turkey (25%) meat samples, respectively. The concurrent occurrence of A. butzleri + C. jejuni + S. aureus bacteria amid the examined poultry meat samples was 2.08%.The occurrence of A. butzleri, S. aureus,C. jejuni, and L. monocytogenes in poultry meat samples. Adequate cooking of poultry meat can diminish foodborne diseases due to A. butzleri, S. aureus, L. monocytogenes, and C. jejuni bacteria, and these species may constitute a public health problem.This is an initial report of Poultry meat is an excellent source of many minerals and vitamins. The human contribution to poultry meat inspection and purchase increased the probability of bacterial contamination and complicated foodborne diseases .Campylobacter, Salmonella, Escherichia, Arcobacter, Listeria, and others [Staphylococcus aureus (S. aureus) is a Gram-positive bacterium that originates from the respiratory tract and on the skin and handles unadorned nosocomial and community-acquired infections and foodborne diseases [S. aureus .Some pathogens source the greatest cases of foodborne infection, e.g., d others \u20135. Staphdiseases . Many gaListeria monocytogenes (L. monocytogenes) is a Gram-positive bacterium that can cause severe diseases, including meningoencephalitis, septicemia, mastitis, metritis, keratoconjunctivitis, iritis, and abortion in humans and animals, principally distressing newborn, pregnant, and immunocompromised persons [ persons . It is a persons .Campylobacter species are Gram-negative bacteria and are considered the most common gastroenteritis. Campylobacter jejuni (C. jejuni) is this genus\u2019s most significant bacterium, accompanied by human diseases [diseases . Clinicadiseases .Arcobacter species are Gram-negative bacteria of the Campylobacteraceae family. Arcobacter butzleri (A. butzleri) is one of the most important species in the genus Arcobacter. Arcobacter butzleri has developed as a significant foodborne zoonotic bacterium responsible for diverse clinical syndromes [yndromes .S. aureus, C. jejuni, A. butzleri, and L. monocytogenes [S. aureus, C. jejuni, A. butzleri, and L. monocytogenes [Poultry meat and its products are measured as reservoirs of ytogenes ,8. Poultytogenes ,8. Thus,S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in poultry meat in Iran. There is inadequate data to rule out the occurrence of S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in poultry meat in Iran. Thus, a current survey was done to measure the occurrence of S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in ostrich, turkey, chicken, and quail meat samples collected from Shahrekord, Iran.Alterations in recovery rates of food contamination between some studies on poultry products from different countries have been reported ,2,7\u20139. TThe survey rendered the procedure accepted by Islamic Azad University, Shahrekord Branch, Shahrekord, Iran.n = 24), turkey (n = 24), chicken (n = 24), and quail (n = 24), were collected from the retail centers of Shahrekord, Iran. Sampling was done from the femur muscles of poultry. The 40 gm of samples in sterile glass bottles) were rapidly transferred to the laboratory at 4\u00b0C.From May to August 2019, 94 raw poultry meat samples, including ostrich using Stomacher . Afterward, samples (5 ml) were added to Trypticase Soy Broth (50 ml) containing NaCl 10%) and sodium pyruvate (1%). Incubation was done at 35\u00b0C for 18 h. Afterward, a loopful of culture was transferred into Baird-Parker agar containing egg yolk tellurite emulsion. Incubation was carried out for 24 h at 37\u00b0C. % and sodListeria enrichment broth . Incubation was carried out for 24 h at 37\u00b0C. Afterward, a milliliter of samples was transferred to Frazer broth (9 ml) . Incubation was carried out for 24 h at 37\u00b0C. PALCAM agar and Oxford agar media were used for other enrichment. Incubation was done for 48 h at 35\u00b0C. Three black colonies with black sunken were cultured on Tryptone Soy agar containing yeast extract (0.6%). Incubation was carried out for 24 h at 37\u00b0C. Listeria monocytogenes was identified by biochemical tests [A similar volume of samples was primarily homogenized with 225 ml of al tests .Campylobacter selective supplement IV . Microaerophilic incubation was done for 24 h at 42\u00b0C. Afterward, the enrichment (0.1 ml) was added to Campylobacter selective agar , which contained a specific antibiotic and sheep blood (5%) [A similar volume of samples was primarily homogenized with 225 ml of Preston enrichment broth containing sheep blood (5%) and ood (5%) .Arcobacter broth containing trimethoprim (64 mg/l), amphotericin B, novobiocin (32 mg/l), cefoperazone, 5-fluorouracil (100 mg/l), and teicoplanin . Incubation was done for 48 h at 30\u00b0C. Afterward, bacteria were transferred to Arcobacter agar containing the same ingredients as above and sheep blood. Incubation was done for 48 h at 30\u00b0C. Acobacter butzleri was identified by biochemical tests [A similar volume of samples was primarily homogenized with 225 ml of al tests .p < 0.05 was determined as a numerically significant level.A numerical examination was performed using SPSS 21.0 . The chi-square and Fisher\u2019s exact two-tailed tests were performed to analyze the data. S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in ostrich, turkey, chicken, and quail meat samples. A. butzleri, C. jejuni, L. monocytogenes, and S. aureus in examined poultry meat samples was 11.45%, 17.70%, 1.04%, and 16.66%, respectively. The technique failed to detect any L. monocytogenes bacteria in the ostrich, turkey, and chicken meat samples. Additionally, only one quail sample (4.16%) was positive for L. monocytogenes. The highest A. butzleri was found in chicken meat samples (25%). The highest occurrence of C. jejuni was found in turkey meat samples (25%). The highest occurrence of S. aureus was found in turkey meat samples (25%). A statistically significant difference was obtained between the type of poultry meat samples and bacteria (p < 0.05).The current research assessed the occurrence of A. butzleri + C. jejuni, A. butzleri + S. aureus, C. jejuni + L. monocytogenes, C. jejuni + S. aureus, L. monocytogenes + S. aureus, and A. butzleri + C. jejuni + S. aureus bacteria amid the examined poultry meat samples was 4.16%, 4.16%, 1.04%, 4.16%, 1.04%, and 2.08%, respectively. The applied method failed to detect A. butzleri + L. monocytogenes bacteria in all poultry meat samples. Chicken meat samples had the uppermost occurrence of A. butzleri + C. jejuni (12.50%). Chicken meat samples had the highest A. butzleri + S. aureus (8.33%). Turkey meat samples had the highest C. jejuni + S. aureus (8.33%). A statistically significant difference was obtained between poultry meat samples and the combined occurrence of bacteria (p < 0.05).Staphylococcus aureus, C. jejuni, A. butzleri, and L. monocytogenes are essential pathogens in gastrointestinal, foodborne, and nosocomial infections [Staphylococcus aureus is a significant cause of foodborne diseases, causing an estimated 240,000 diseases in the United States [Campylobacter species in the European Union was 225,000 in 2011. However, it could be as high as 10 million a year [L. monocytogenes is an imperative foodborne pathogen contributing to 1,700 foodborne diseases, 1,500 hospitalizations, and 250 deaths [Arcobacter species, especially A. butzleri, is associated with several outbreaks of foodborne diseases globally [Foodborne diseases in the United States cause yearly, about 75 million diseases, 300,000 hospitalizations, and 6,000 deaths . Staphylfections . Staphyld States ,15. The n a year . In the 0 deaths . Arcobacglobally .S. aureus, C. jejuni, A. butzleri, and L. monocytogenes bacteria amid the raw ostrich, turkey, chicken, and quail meat samples collected from Shahrekord, Iran. Outcomes revealed that the bacteria of S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in the examined raw poultry meat samples were 16.66%, 17.70%, 11.45%, and 1.04%, respectively. Thus, C. jejuni had the highest occurrence. Additionally, the uppermost occurrence of A. butzleri, C. jejuni, L. monocytogenes, and S. aureus was found in chicken meat (25%), chicken meat (33.33%), quail meat (4.16%), and turkey meat (25%). The high occurrence of bacteria in examined poultry meat samples may be due to the primary presence of bacteria in studied poultry, the occurrence of cross-contamination through diverse stages of the slaughter, the transmission of bacteria from infected staff and workers to poultry carcasses, and finally, the transmission of bacteria from contaminated water used in the washing of poultry carcasses. Diverse research has been conducted in this field.The current investigation assessed the occurrence of S. aureus was conveyed in foodstuff from Italy [S. aureus in meat in Brazil [S. aureus bacteria was also recognized in samples collected from Australia [S. aureus bacteria. The subordinate occurrence of om Italy and the om Italy . The occn Brazil , Egypt [n Brazil , Germanyn Brazil , and Denn Brazil were 21.ustralia , the Uniustralia , and theustralia . Our finA. butzleri [Arcobacter and contaminate the slaughterhouses throughout carcass processing, thereby preventing additional contamination. The occurrence of Arcobacter in chicken meat samples collected from Iran [Arcobacter strains amid raw chicken, turkey, quail, partridge, duck, ostrich, and geese meat samples were 28.00%, 11.00%, 12.00%, 7.50%, 11.40%, 3.30%, and 8.00%, respectively. He revealed that 90.10% of Arcobacter isolates were related to A. butzleri. de Oliveira et al. [Arcobacter spp. in chicken meat samples was 18.30%, in which 63.60% of isolates were related to A. butzleri. Molva and Atabay [Arcobacter species amid the chicken meat samples was 55%, in which 80% of isolates were A. butzleri.Poultry is an imperative reservoir of butzleri \u201330. It ibutzleri ,29. Poulrom Iran , Nigeriarom Iran , Malaysirom Iran , The Netrom Iran , Korea [rom Iran , and Sparom Iran was 37.5a et al. conveyedListeria monocytogenes has a lower occurrence in comparison with other tested bacteria. Perkovi\u0107 et al. [L. monocytogenes among the poultry meat samples was 1%. Turkey meat was the most commonly contaminated (2%). Osaili et al. [L. monocytogenes was recovered from 9.40% of raw broiler samples, higher than our findings. Meyer et al. [Listeria species were isolated from 6% of poultry meat product samples, which was also higher than our findings. In keeping with this, various occurrence rates of L. monocytogenes have been reported worldwide, ranging from 8% to 99% [L. monocytogenes in turkey meat samples was 12.70% [\u0107 et al. specifiei et al. specifie% to 99% ,41,42. S% to 99% describe% to 99% conveyeds 12.70% .Campylobacter jejuni is well adapted to growth and survival in poultry meat and dependent products. Mezher et al. [Campylobacter species in chicken meat samples were 6.80%, and 27.27% of isolates were identified as C. jejuni. The whole occurrence of C. jejuni amid the poultry meat samples collected from Iraq [Campylobacter species was also conveyed in poultry meat samples collected from European countries (29%\u201341%) [r et al. found throm Iraq , Iran [4rom Iraq , Pakistarom Iraq , India [rom Iraq , Korea [rom Iraq , and Chirom Iraq was 10%,29%\u201341%) \u201355.As observed, diverse research reveals various occurrence rates of bacteria. The variance in data suggests that season, time and place of sampling, method of sampling, types of samples, and even laboratory methods applied in research may affect the outcomes of an occurrence rate. Different hygienic levels of poultry flocks and shopping centers may affect bacteria in diverse investigations.S. aureus, C. jejuni, A. butzleri, and L. monocytogenes foodborne bacteria in raw ostrich, turkey, chicken, and quail meat samples. The occurrence of A. butzleri, C. jejuni, L. monocytogenes, and S. aureus in examined poultry meat samples was 11.45%, 17.70%, 1.04%, and 16.66%, respectively, which was notable. Furthermore, chicken and turkey had a higher contamination rate. Some samples were simultaneously contaminated with two or three foodborne bacteria, demonstrating the boosted importance of poultry meat as a reservoir of pathogenic bacteria. An existing survey is an initial report of A. butzleri, C. jejuni, L. monocytogenes, and S. aureus in ostrich, turkey, chicken, and quail meat samples. Our findings revealed that only quail meat was a reservoir for L. monocytogenes. Appropriate timing and adequate temperature for poultry meat samples can reduce the risk of transmission of A. butzleri, C. jejuni, L. monocytogenes, and S. aureus bacteria to humans. Nevertheless, supplementary surveys can determine additional information regarding A. butzleri, C. jejuni, L. monocytogenes, and S. aureus bacteria in poultry meat.An existing survey assessed the occurrence of"} +{"text": "Aphis (Toxoptera) fafuensis Cheng & Huang, sp. nov., feeding on Adinandramillettii (Pentaphylacaceae) from Fujian, China, and Aphis (Toxoptera) sennae Cheng & Huang, sp. nov., feeding on Sennabicapsularis (Fabaceae) from Yunnan, China, were described. Morphological characters and molecular data supported the taxonomic position of the new species within the subgenus Aphis (Toxoptera). A key for identifying species of apterous viviparous females in this subgenus is provided.Two new aphid species, Toxoptera was first proposed by T.aurantiae Koch, 1856 designated as the type species. However, the name was considered as a synonym and the type species was revised as T.aurantii Boyer de Fonscolombe, 1841 by Toxoptera as having alate with once-branched media of the forewing. Schizaphis to include species characterized by the once-branched media of the forewing, Toxoptera had been distinguished from allied genera by the presence of the stridulatory apparatus.The aphid genus Aphidini using several gene markers including tRNA/COII, 12S/16S and EF1-\u03b1, and their results showed that Toxoptera may be non-monophyletic. Based on COI sequences, T.odinae was phylogenetically distinct from other Toxoptera species and should be reverted to Aphis (Aphis) odinae van der Goot, 1917 has been represented by five species (A. (T.) aurantii Boyer de Fonscolombe, 1841, A. (T.) celtis Shinji, 1922, A. (T.) citricidus Kirkaldy, 1907, A. (T.) victoriae Martin, 1991 and A. (T.) chaetosiphon Qiao, Wang & Zhang, 2008. However, it should be noted that A. (T.) celtis is considered a possible synonym of A. (T.) aurantii aurantii feeding on Ficus showed great genetic difference from those feeding on other host plant groups, indicating that A. (T.) aurantii has been undergoing the evolution of host specialization on Ficus.Thus far, the subgenus species : A. (T.)aurantii . The hoseciation . Based oAdinandramillettii (Hook. & Arn.) Benth. & Hook. f. ex Hance (Pentaphylacaceae) and Sennabicapsularis (L.) Roxb. (Fabaceae), respectively. By integrating morphological and molecular data, this paper describes the new species and confirms their taxonomic positions within Aphis (Toxoptera).In recent years, while collecting aphid samples in southern China, we obtained some samples that may represent two undescribed species from A. (T.) fafuensis Cheng & Huang, sp. nov. were collected in Fujian, China on Adinandramillettii and the samples of A. (T.) sennae Cheng & Huang, sp. nov. were collected in Yunnan, China on Sennabicapsularis. The detailed collection information is provided in Suppl. material The specimens of A. (T.) fafuensis Cheng & Huang, sp. nov. and eight apterous viviparous females of A. (T.) sennae Cheng & Huang, sp. nov. were slide-mounted in Canada Balsam. Aphid terminology and the morphological measurements used in this paper followed Six apterous viviparous females of BL, body length;BW, body width;URS, ultimate rostral segment;URS_BW, basal width of URS;WR, whole length of rostral;WA, whole length of antenna;Ant. I, Ant. II, Ant. III, Ant. IV, Ant. V, Ant. VIb, for antennal segments I, II, III, IV, V and the base of Ant. IV, respectively;Ant. III_WD, the widest diameter of Ant. III;PT, processus terminalis;PT_WD, the widest diameter of PT;HF, hind femur;HF_WD, the widest diameter of HF;HT, hind tibia;HT_WD, the widest diameter of HT;2HT, second hind tarsal segment;SIPH, siphunculus;SIPH_BW, basal width of siphunculus;SIPH_DW, distal width of siphunculus;Cauda_BW, basal width of cauda;AP, anal plate;GP, genital plate; gona, gonapophyses.The following abbreviations have been used:A. (T.) aurantii, a one-way analysis of variance (ANOVA) was conducted. Furthermore, to identify pairwise differences of the morphological characters of specimens, post hoc multiple comparisons were performed using the Least Significant Difference (LSD) test was amplified with primer LepF (5\u2019-ATTCAACCAATCATAAAGATATTGG-3\u2019) and LepR (5\u2019-TAAACTTCTGGATGTCCAAAAAATCA-3\u2019) and 2 min at 72 \u00b0C, and 10 min of final extension at 72 \u00b0C. The products of PCR were visualized by electrophoresis on a 1% agarose gel and then bidirectionally sequenced at Beijing Tsingke Biotech Co., Ltd. .The whole genomic DNA of each sample was extracted from the single individual preserved in 95% ethanol using the DNeasy Blood & Tissue Kit . The standard DNA barcode gene of aphids, cytochrome c oxidase subunit I (ATCA-3\u2019) . PCR ampCOI sequences includes thirty-six samples representing the two new species and three Aphis (Toxoptera) species including A. (T.) aurantii, A. (T.) citricidus and A. (T.) chaetosiphon were reconstructed. A. (T.) celtis and A. (T.) victoriae were excluded from the phylogenetic analysis, as A. (T.) celtis did not have any available COI sequence and the sequences of A. (T.) victoriae in GenBank did not provide enough sites for analysis after alignment with other sequences. Aphis (Aphis) gossypii Glover, 1877 and Aphis (Aphis) odinae were used as outgroups model model .The holotypes and paratypes of the new species and all the other specimens examined here are deposited in the Insect Systematics and Diversity Lab, Fujian Agriculture and Forestry University, Fuzhou, China.Taxon classificationAnimaliaHemipteraAphididae\ufeffCheng & Huangsp. nov.340608E9-F6AF-5482-AAEC-05C2EAFEDA6Chttps://zoobank.org/13AFFC64-CF53-4E58-8953-6FA9067D43A5Apterous viviparous females: Body elliptical Fig. , dark brHead.Mounted specimens: Vertex convex, antennal tubercles slightly developed. Head with one pair of cephalic hairs, one pair of antennal tubercular hairs. Dorsum of head smooth with 4\u20137 hairs. Dorsal hairs of head fine, and with developed small tubercles at bases. Antennae six-segmented, segments I and II dark brown, segments III\u2013VIb and PT dark at distal end and with spinulose imbrications; 0.8\u20131.0 times as long as body. Length in proportion of segments I\u2013VI: 21\u201333, 21\u201328, 100, 61\u201376, 65\u201372, 26\u201333 + 107\u2013138. Processus terminalis 3.8\u20134.6 times as long as basal part of the segment. Antennal hairs acute, segments I\u2013VI each with 5\u20136, 3\u20134, 4\u20138, 3\u20135, 2\u20134, 3 + 5\u20136 hairs, respectively, apical part of processus terminalis with 0\u20134 hairs. Length of hairs on segment III 0.01 mm, 0.5 times as long as the widest diameter of segment III. Rostrum long, apical part dark brown, reaching hind coxae or abdominal segment I. Ultimate rostral segment wedge-shaped, 2.2\u20132.8 times as long as basal width, 1.4\u20131.8 times as long as second hind tarsal segment. Ultimate rostral segment with four pairs of hairs, including one pair of accessory hairs.Thorax. Dorsal and ventral cuticle with polygon reticulations. Mesosternal furca with separated arms. Length of single arms 0.09\u20130.11 mm, 0.4\u20130.5 times as long as antennal segment III. Spiracles elliptical, spiracular plates dark brown. Prothorax with one pair of small marginal tubercles. Dorsal setae on thorax short and pointed, with small tuberculate bases. Legs normal. Distal part of femora, basal and distal part of tibiae dark brown, others brown. Hind femur 1.3\u20131.6 times as long as antennal segment III, hind tibia 0.5\u20130.6 times as long as body. Hind tibia with 7\u20138 peg-shaped spines, on basal two-thirds of inner side. Length of hairs on hind tibia 0.02\u20130.03 mm, 1.0\u20131.5 times as long as the widest diameter of antennal segment III. First tarsal chaetotaxy: 3, 3, 2. Second tarsal segments with transverse imbrications.Abdomen. Abdominal segments IV\u2013VI with ventro-lateral spinulose ridges, forming a stridulatory surface. Marginal tubercles on abdominal segments I and VII. Abdominal dorsal hair sparse, fine, with tuberculate bases. Abdominal tergite VIII with two hairs. Siphunculi dark brown, cylindrical, with broad base, tapering towards the apex, with spinulose transverse imbrications, without flange or hairs. Siphunculi 0.12\u20130.17 mm, 1.9\u20132.8 times as long as its basal diameter, 0.9\u20131.2 times as long as cauda. Cauda short tongue-shaped, constricted in middle, 1.4\u20132.3 times as long as its basal diameter, with 14\u201321 hairs. Anal plate broad and round, with 18\u201321 hairs. Genital plate transversely oval, with 11\u201318 hairs. Cauda, anal plate and genital plate dark brown with dense spinules. Gonapophyses three, each with 3\u20135 hairs.Holotype: apterous viviparous female, China: Fujian , 27 June 2016, No. HL_20160627_3_A, on Adinandramillettii, coll. X. L. Huang and X. L. Lin (FAFU). Paratypes: 4 apterous viviparous females , China: Fujian , 17 May 2015, on Adinandramillettii, coll. X. L. Huang and X. L. Lin (FAFU).Aphis.The new species is named after FAFU, the abbreviation for Fujian Agriculture and Forestry University, where the samples of this species were first discovered and collected. And \u2018fafuensis\u2019 is an adjective of feminine gender in accord with the feminine Adinandramillettii (Hook. & Arn.) Benth. & Hook.f. ex Hance (Pentaphylacaceae).China: Fujian Province .Crematogaster fafuensis Cheng & Huang, sp. nov. has black-and-white banded antennae. Siphunculi and cauda are dark. Most part of femora, basal and distal parts of tibiae are dark brown. The peg-like spines on the hind tibiae and roughened ventro-lateral cuticle on the posterior part of the abdomen form a typical stridulatory apparatus. Compared with A.aurantii, the new species has a smaller body size and stubbier siphunculi: body length 0.91\u20131.19 mm (A.aurantii: 1.14\u20131.71 mm), siphunculi length 1.9\u20132.8 times of siphunculi basal width (A.aurantii: 2.0\u20133.8 times). The results of ANOVA analysis showed that there were significant differences between A. (T.) fafuensis Cheng & Huang, sp. nov. and A. (T.) sennae Cheng & Huang, sp. nov. and A. (T.) aurantii in some characters, such as the length of URS_BW, and the ratios of Ant. I and Ant. II to WA , 11 Nov. 2017, No. HL_zld20171111_7_A, on Sennabicapsularis coll. L. D. Zeng (FAFU). Paratypes: 7 apterous viviparous females , with the same collection date as holotype (FAFU).Sennabicapsularis. The word \u2018sennae\u2019 is a noun, and does not change spelling based on gender.The new species is named after the genus name of the host plant, Sennabicapsularis (L.) Roxb. (Fabaceae).China: Yunnan Province (Kunming).It seems the species feeds on seed pods of the host plant.Aphis (T.) sennae Cheng & Huang, sp. nov. has black-and-white banded antennae, and processus terminalis are dark, different from A.aurantii whose processus terminalis are dark basally and distally. Siphunculi length 1.9\u20132.7 times of siphunculi basal width (A.aurantii: 2.0\u20133.8 times). The body length of A. (T.) sennae Cheng & Huang, sp. nov. is 1.50\u20131.89 mm, which is significantly larger than A. (T.) fafuensis Cheng & Huang, sp. nov. (0.91\u20131.19 mm). Body color of A. (T.) sennae Cheng & Huang, sp. nov. is reddish brown, the head is slightly darker, and immatures are almost the same color as adult apterae. Adult apterae of A.aurantii and A. (T.) fafuensis Cheng & Huang, sp. nov. are brownish-black, the nymphs of these two species are lighter in body color, or reddish brown. The results of ANOVA analysis and the LSD test revealed significant differences between A. (T.) sennae Cheng & Huang, sp. nov. and A. (T.) fafuensis Cheng & Huang, sp. nov., as well as between A. (T.) sennae Cheng & Huang, sp. nov. and A. (T.) aurantii, in a number of characters, including the measured length, ratio, and number of hairs on various body parts fafuensis and A. (T.) aurantii was 2.8%, and the K2P distances between A. (T.) fafuensis and other species from Aphis (Toxoptera) ranged from 5.6% to 9.2%. Meanwhile, the mean interspecific distance between A. (T.) sennae and A. (T.) aurantii was 2.7%, and the K2P distances between A. (T.) sennae and other species within Aphis (Toxoptera) ranged from 4.5% to 8.2%. The averages of pairwise sequence divergences of the COI genes among thirty-six samples are presented in Table The mean interspecific distance between A. (T.) fafuensis Cheng & Huang, sp. nov. and A. (T.) sennae Cheng & Huang, sp. nov. clustered together with the known species of Aphis (Toxoptera). Both the two new species showed morphologically and phylogenetically closer relationships with A. (T.) aurantii and A. (T.) fafuensis had a sister relation with A. (T.) aurantii, probably due to closer relationship of their host plants.The phylogenetic results showed that"} +{"text": "Iris sect. Psammiris comprises rhizomatous perennials distributed in the north temperate zone of Eurasia. The systematics of the section are currently based on morphology, and the phylogenetic relationships within it still remain unclear. In the framework of Iris systematics, we conducted molecular and morphological analyses of the currently recognized I. sect. Psammiris species to elucidate the taxonomic composition and relationships within the section. The phylogenetic reconstructions based on sequence variation of four noncoding chloroplast DNA regions support the monophyly of I. sect. Psammiris, which includes I. tigridia, while I. potaninii var. ionantha belongs to I. sect. Pseudoregelia. The proposed novel classification of I. sect. Psammiris recognizes three series: an autonymic series with I. humilis, I. bloudowii, and I. vorobievii and two unispecific series (I. ser. Potaninia with I. potaninii and I. ser. Tigridiae with I. tigridia). In addition, the taxonomic statuses of I. arenaria, I. ivanovae, I. kamelinii, I. mandshurica, I. pineticola, I. psammocola, and I. schmakovii are clarified herein. We provide a revised taxonomic treatment for I. sect. Psammiris, including notes on the types; updated information on species synonymy, distributions, habitats, and chromosome numbers; and a new identification key to the species. Three lectotypes are designated here. Iris L. (Iridaceae) that comprises rhizomatous perennials distributed exclusively in the north temperate zone of Eurasia and found in sandy soils of steppes, open meadows, and hillsides. As the most cold-resistant among I. subgen. Iris (bearded irises), psammirises have always attracted attention as garden plants ad Baikal, [fl.], 1772, [Georgi] s.n. Herb. C.B. Trinius .\u2014https://plant.depo.msu.ru/open/public/en/item/MW0021793 (accessed on 20 December 2022).(1) Iris flavissima Pall., Reise Russ. Reich. 3(2): 715, 1776.\u2014Lectotype .\u2014https://data.nhm.ac.uk/dataset/collection-specimens/resource/05ff2255-c38a-40c9-b657-4ccb55ab2feb?q=BM000832584 (accessed on 20 December 2022).= Alexeeva (p. 917)Iris mandshurica Maxim., Bull. Acad. Imp. Sci. Saint-P\u00e9tersbourg 26(3): 530, 1880.\u2014Lectotype .\u2014http://re.herbariumle.ru/01025688 (accessed on 20 December 2022).= Alexeeva (p. 417)Iris arenaria Waldst. et Kit., Descr. Icon. Pl. Hung. 1: 57, 1802 \u2261 I. humilis subsp. arenaria \u00c1.L\u00f6ve et D.L\u00f6ve, Bot. Not. 114(1): 51, 1961.\u2014Lectotype .= Alexeeva (p. 207)Kitaibel (t. 57).Iris flavissima subsp. stolonifera f. orientalis Ugr., Trudy Obsc. Isp. Prir. Imp. Har\u2019kovsk. Univ. 44: 305, 1911 \u2261 I. pineticola Klokov, Fl. URSR 3: 407, 1950.\u2014Lectotype (designated here by E.V. Boltenkov): [illustration] \u201cIris flavissima Pall. I. B. orientalis Ugr.\u201d in Ougrinsky , 6 July 2007, R.V. Kamelin et al. 23 [originally in Russian] (LE01042608!).\u2014http://re.herbariumle.ru/01042608 (accessed on 20 December 2022).= Iris humilis is the most widely distributed and northernmost of I. subgen. Iris and is the only arillate iris native to Europe. Its range stretches along the Eurasian steppe belt from Europe to the Pacific coast, including the steppe patches of southern Siberia and the Russian Far East. It is found from Central and Eastern Europe , including the Central Black Earth Economic Region and eastern oblasts of the Volga region and Pre-Urals, to southern Siberia, Russia, and northern Kazakhstan, as well as in northern Mongolia, northeastern China , North Korea , southern Russian Far East, and eastwards to the Pacific coast, where it has been recorded from dunes near the Kievka River estuary . The northernmost wild locality of I. humilis has been found in vicinities of Kochegarovo Village . Iris humilis is characterized by good adaptation to sandy, stony, clayey, limestone, and humus-rich soils. It grows commonly in open places in steppes and meadows, on slopes, at edges of pine forests, and along river banks at elevations of 350\u20131850 m.Distribution and habitat: n = 22, 24, 26, and 28 (see below).Chromosome numbers: 2Iris\u00a0bloudowii Ledeb., Icon. Pl. [Ledebour] 2: 5, 1830 \u2261 I. flavissima \u03b1 [var.] umbrosa Bunge, Fl. Altaic. [Ledebour] 1: 60, 1829, excl. syn. \u2261 I. flavissima var. bloudowii (Ledeb.) Baker, Handb. Irid.: 29, 1892.\u2014Lectotype .\u2014http://re.herbariumle.ru/01010770 (accessed on 20 December 2022).(2) v et al. (p. 31))Distribution and habitat: This species is found in the Altai-Sayan region, Northern Tian Shan (Dzhungraian Alatau and Kungey Alatau) and Inner Tian Shan (Terskey Ala-Too) and is distributed in northern Kyrgyzstan (Issyk-Kul Region), eastern Kazakhstan , Russia , and northwestern China (Xinjiang). It grows on grassy subalpine and alpine meadows, among shrubs and in shady places, on hillsides or at forest edges, and along mountain streams at elevations of 850\u20132200 m.n = 16 Primorsky Krai, Khasansky District, on the way to Kraskino Village, hill slopes, [fl.], 2 June 1964, Stepanova et al. s.n. [originally in Russian] .\u2014(3) Distribution and habitat: This species is known only from a limited area in southern Russian Far East (southern Khasansky District), northern North Korea, and northeastern China (northeastern Jilin Province). It is found growing in open places with good drainage, on loamy sand soil with gravel on grassy slopes, and on shingly meadow terraces near sea coasts at elevations up to 10 m.n = 14 (sub I. mandshurica) Transbaikalia, near Troitskosavsk [Kyakhta], shtab-lekarskaya zaimka, at 10 versts from the city, [fl.], 21 May 1915, P. Mikhno s.n. [originally in Russian] .\u2014= Iris psammocola Y.T. Zhao, Acta Phytotax. Sin. 30(2): 181, 1992, syn. nov.\u2014Holotype: [China] , [fl.], 10 April 1959, s.coll. s.n. [originally in Chinese] (NENU00014009!).\u2014= Iris kamelinii Alexeeva, Novosti Sist. Vyssh. Rast. 38: 116, 2006, syn. nov.\u2014Holotype: [Russia] Altai Republic, Kosh-Agachsky District, Chikhachev Range, Boguty Lake, the northern gravelly macroslope, 2500 m a.s.l., 6 July 2001, N.B. Alexeeva et al. 11 [originally in Russian] (LE01010775!).\u2014http://re.herbariumle.ru/01010775 (accessed on 20 December 2022).= I. potaninii known to us has been recorded from the upper Barguzin Depression in the Republic of Buryatia, Russia . As reported in 1: 60, 1829.\u2014Lectotype (designated here by E.V. Boltenkov): Altai, in schistosis ad fluvium Tscharysch, [fl.], [4 May] 1826, Bunge 50, Herb. C.A. Meyer .\u2014http://re.herbariumle.ru/01010797 (accessed on 20 December 2022).(5) Iris ivanovae Doronkin, Fl. Sibir. (Arac.-Orchidac.) 4: 117, 1987.\u2014Holotype: Chita Oblast, Borzinskiy District, Kharanor, feather-grass steppe, [fl.], 7 June 1965, A. Zarubin s.n. [originally in Russian] .\u2014https://www.jacq.org/detail.php?ID=525145 (accessed on 20 December 2022).= Distribution and habitat: This species is distributed in southern Siberia, Russia , eastern Kazakhstan (East Kazakhstan Region), northern Mongolia, and China . It grows in gravelly, stony, or sandy places in steppes among grasses, as well as on dunes, rocky slopes, and often on hilltops at elevations of 400\u20131200 m.n = 38 [n = 20, 24, 32, and 40 [Chromosome numbers: 2n = 38 ,59. The , and 40 ,60, thouI. sect. Psammiris species recognized in the present study.Below is a key to the Iris tigridia1. Stem > 2.5 cm tall, 1-flowered; perianth tube < 2.5 cm long; flowers of various shades of violet, blue, purple, and lilac . . . 1\u2032. Flowers yellow . . . 2Iris potaninii2. Stem < 2.5 cm tall, 1-flowered; perianth tube > 3.5 cm long . . . 2\u2032. Stem > 3.5 cm tall, several-flowered, simple or branched; perianth tube < 1.8 cm long . . . 3Iris vorobievii3. Stem simple (2-flowered), or with 1\u20132 1-flowered branches; rhizome shortened; roots obconical, storage-like . . . 3\u2032. Stem simple; rhizome creeping; roots gradually tapering to apex . . . 4Iris humilis4. Stem with 2\u20133 flowers and 0\u20133 bracteoles . . . Iris bloudowii4\u2032. Stem with 2 flowers and 1 bracteole . . . Iris sect. Psammiris, a number of taxonomic problems in this section remain unresolved. Here, we present the first comprehensive molecular phylogeny of the section, with a large set of samples covering most of the distribution ranges and type localities of the species and almost all of its previously recognized taxa. The results obtained in the present study confirm that all previous data, based solely on morphological characters, do not fully clarify the taxonomic composition and phylogenetic relationships among the I. sect. Psammiris species. Our results based on cpDNA data provide a number of novel insights. The important finding is that the phylogenetic results strongly support the monophyly of I. sect. Psammiris and the placement of I. potaninii var. ionantha in the I. sect. Pseudoregelia clade, which is sister to I. sect. Psammiris. It should also be emphasized that the taxonomy of I. potaninii var. ionantha requires further research. Furthermore, the molecular studies confirm the placement of I. tigridia in I. sect. Psammiris rather than in I. sect. Pseudoregelia.Although many specialists have carried out extensive studies of I. arenaria, I. humilis, I. mandshurica, I. pineticola, and I. schmakovii) should be treated as a single species, i.e., I. humilis; (2) the specimen listed in reference [I. psammocola from Russia and other studied samples from the Tsugeer-Els area , also referred to as I. psammocola, belong to I. potaninii; (3) a critical evaluation of the original material and literature showed that I. psammocola and I. potaninii are the same taxon; (4) the specimens of I. kamelinii from the type locality and from Mongolia [I. potaninii; (5) the molecular data and a critical examination of the type material and living plants from the type locality confirm that I. ivanovae, which has been recognized on the basis of morphology, is a synonym of I. tigridia. In view of the findings reported above, we provide an updated classification of I. sect. Psammiris. The section is unambiguously subdivided into an autonymic series with three species and two unispecific series: I. ser. Potaninia with I. potaninii and I. ser. Tigridiae with I. tigridia. Thus, here, we present a new taxonomic treatment for I. sect. Psammiris and an identification key for all of its species. The members of this section are distributed from southeastern Europe through southern Siberia, northern Kazakhstan, China, and Mongolia to the Russian Far East. The results presented herein will undoubtedly contribute to our understanding of the phylogenetic relationships within Iris s.l. and the taxonomic composition of the genus in Russia and adjacent areas.Other our results are, in general, as follows: (1) five species (eference as I. psMongolia also bel"} +{"text": "Adv. Sci. 2022, 9, 210431710.1002/advs.202104317DOI: In the original published article the structure of the chemical compound reported in Figure"} +{"text": "Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships. Human longevity is a complex trait that is influenced by environmentalfactors, lifestyle, random events, and individualgenetic traits. Studies have shown that genetics plays a significantrole in longevity, with individuals from families of longlivershaving a higher chance of living longer . However, identifying specific genetic determinantsassociated with longevity has been challenging. Currently,only two genes, APOE and FOXO3A, have been shown to beimportant for human longevity across different samples andresearch groups . Other results have beeninconsistent, possibly due to population differences and theeffect of multiple comparisons.Despite the difficulty in identifying specific genetic determinants,maintaining body health is crucial for longevity.Aging of the brain and the development of cerebrovascularand neurodegenerative diseases are major causes of disabilityand death in older adults . However, thegenetic basis of age-related brain diseases is complex andinconsistent. In contrast to qualitative characteristics of thegenome, quantitative traits such as telomere length, the numberof mitochondrial DNA copies, the frequency of heterozygousvariants of mitochondrial DNA, and the frequency of somaticmutations are less affected by population and statistical factors.Despite their importance, little attention has been paidto these quantitative traits in the study of the genetic basis oflongevityThis review aims to analyze existing information on quantitativegenetic traits affecting aging and human longevity.In recent years, there has been much interest in the role ofmtDNA as a determinant of aging, lifespan processes, and agerelateddiseases. Mitochondrial dysfunction is considered oneof the key aging biomarkers , and changesin quantitative and qualitative characteristics of mtDNA aredirectly associated with longevity. Given the spatial proximityof mtDNA to the electron transport chain, it is exposed to thedamaging effects of free radicals, which, along with a limitedability to repair, due to the fact that mtDNA is not protected byhistones and is in a single-stranded form for a considerable partof its replication time, determines the vulnerability of mtDNAstructure to damage and degradation. All of these factorslead to a higher rate of chemical modifications and mutationaccumulation in mtDNA compared to the cell nucleus DNA.Damage and deletion of mtDNA sites can lead tomitochondrial dysfunction due to an increased proportionof molecules containing an extensive deletion (mtDNAdel),since mtDNA with an extensive deletion has a replicativeadvantage over wild-type mtDNA . The replicative advantage is probably determined bythe smaller size of the replicating molecule, which leads toa higher replication rate , and at the same time,a lower chance of damage to the molecule by active oxygenspecies. This results in less active mitophagy of mtDNAdelrichorganelles compared to normal organelles . Moreover, whereas in actively proliferating tissues,cells containing dysfunctional mitochondria are subject toelimination and replacement, tissues characterized by a highnumber of postmitotic cells accumulate a burden of suchmutations, which probably leads to a decrease in the functionalparameters of the tissue .The proportion of mtDNAdel in muscle tissue has beenshown to increase approximately 19-fold, from 0.008to 0.15 %, from 50 to 86 years . A similarphenomenon has been observed in nerve tissue . It has also been noted that significant accumulation ofmtDNAdel is observed in patients with Parkinson\u2019s diseasein substantia nigra neurons and the striatum . Moreover,there is an opinion that accumulation of mtDNAdel can triggerneuroprotective mechanisms .The state of mtDNA heterogeneity in which severalclones of mtDNA with different nucleotide sequences existin mitochondria is called heteroplasmy. It is known thatheteroplasmy can occur either de novo during ontogenesis orby maternal inheritance . Heteroplasmicmutations also appear to be associated with macroinflammation. For example, R. Zhang and colleagues notedthat, on average, individuals over the age of 70 had 58.5 %more mtDNA heteroplasmic mutations than individuals underthe age of 40 . This fact becomes of greatsignificance when we consider that there is substantial evidencelinking mtDNA heteroplasmy with neurodegenerative diseasesdirectly associated with longevity: Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD) . At the same time, there are reports showing apositive role of heteroplasmy for longevity , which is probably because mtDNAheteroplasmy is a reservoir of genetic variability that canintroduce new functions and increase the ability of cells to cope with environmental and physiological stressors duringlife. It can be assumed that both of these phenomena takeplace and their importance for longevity is determined by thelocalization of somatic mtDNA mutation accumulation andby the fact that congenital heteroplasmy can have a positiveeffect to a greater extent, while acquired one has a greaterchance to carry negative properties.Another mitochondrial marker likely associated withlongevity may be the frequency of accumulation of mitochondrialsomatic mtDNA (mtSNV) A>G mutations in themtDNA heavy chain. In a recent study , the authors determined a positive correlation betweenthe frequency of AH>GH (H \u2013 heavy chain) substitutionsand the lifespan of different mammalian species: the morelong-lived a species is, the higher the frequency of AH>GHsubstitutions is observed in it. At the same time, the authorssuggest that the observed accumulation of GH nucleotides isa consequence of oxidative mutagenesis and aging processesrather than a cause.The half-life of mtDNA also seems to be an importantfactor determining the rate of tissue dysfunction onset. It hasbeen suggested that cell lifespan depends on mtDNA half-life. In modeling theeffect of half-life on cell survival time, it has been determinedthat a moderate increase in mtDNA half-life has a profoundeffect on increasing cell survival time, thereby reducing thereplicative advantage of mtDNA with extensive deletions. Equally importantly, a decrease inmtDNA half-life significantly affects the process of mtSNVaccumulation in tissues characterized by a high number ofpostmitotic cells. It has been shown that if the half-life is threemonths, pathogenic mtSNV acquired in a neuronal progenitorcell early in development and present in the postmitoticneuronal population at an average frequency of 1 %, by70 years of human life, will be contained in most neurons witha frequency of ~14 % . Accordingly, changingthe half-life rate downward acts to inhibit mitochondrialheteroplasmy levels and vice versa.In addition to mutational events, the mtDNA copy number(mtDNAcn) is an important quantitative trait. Changes inmtDNAcn are usually a reflection of the mitochondrialresponse to oxidative stress and are also associated withgeneral dysfunction. Various studies have reported resultsshowing a decrease in mtDNAcn as humans age . A decrease in mtDNA copies in wholeblood has been found to occur with age, and a lower numberof mtDNA copies is associated with poorer health . High mtDNAcn levels areprobably generally associated with better health outcomesin older individuals, including higher levels of cognitivefunction and lower mortality . It has been noted that a decreased mtDNAcnscore is strongly associated with the risk of age-relatedneurodegenerative diseases such as dementia, PD, AD, etc..It should be noted that both systemic trends toward adecrease in mtDNAcn in individuals with AD and a localdecrease in mtDNAcn by 30\u201350 % in the frontal lobe of thelarge hemisphere cortex and hippocampus compared to healthycontrols have been observed . At the same time, there is a publication that describesan increase in mtDNAcn in patients of African descent withParkinson\u2019s disease .In studies examining changes in mtDNAcn in the bloodleukocytes of long-livers as a model of healthy aging,contradictory results have been obtained. Y.H. He et al. (2014)showed a significant increase in the amount of mtDNAcn incentenarians compared to elderly people ,but van Leeuwen et al. did not observe such a pattern, which may be due to differentmethodological approaches. It should be noted that differenttissues may show different age dynamics of mtDNAcn. Forexample, while an inverse correlation was observed in skeletalmuscle samples, a positive correlation was observed in liveror substantia nigra samples .The mtDNAcn index seems to be related to the telomerelength (TL) parameter . It is assumed that this relationship isbased on the negative correlation between mtDNAcn levelsand levels of reactive oxygen species (ROS) and furthernegative effects of ROS on telomere length .Telomere length is a well-known biomarker of aging . Although the relationship between TL andcellular aging is undeniable in model cell cultures , the conclusions for multicellular organismsare not so unambiguous . It has beensuggested that telomere shortening dynamics, rather thantotal telomere length, can serve as a quantitative biomarker ofmacroorganism lifespan . For example, incross-sectional studies on five bird species, it was shown thatshort-lived bird species lose more telomere repeats with agethan species with longer lifespans . Asimilar correlation has been observed in mammals, suggestingthat long-lived animals have more effective mechanisms ofprotection against replicative aging, such as higher telomeraseactivity throughout life .In humans, shorter telomere length is associated with highermortality rates from various age-related pathologies, includingsome neurodegenerative diseases such as dementia . However, reports on the role of telomere lengthin the risk of AD are ambiguous. Some studies noted that TLlength is lower in people with AD than in control samples, while P. Thomas et al.noted an inverse relationship in some tissues such as thehippocampus. Interestingly, longer telomeres have a negativeeffect on disease dynamics and severity . Short TL is a good prognosticmarker for determining the long-term risk of AD in APOE4-negative individuals . Moreover,TL is associated with cognitive function in both elderly andmiddle-aged individuals .It has been estimated that leukocyte telomeres in adultsshorten at an average rate of 24.7 bp per year . A number of different factors can influence TL and the rate of telomere depletion. For example, TL hasbeen shown to be higher in older women compared to men and in African Americans compared toCaucasians . First of all, it should be notedthat in addition to the large number of studies that have noteda negative correlation of TL with age and the association ofthis parameter with mortality in the older age group, thereare also studies in which these patterns were not confirmed.Initially, it was assumed that such discrepancies areassociated with the peculiarities of specific studies, such as themethodology of sample formation, the presence of populationstratification, the type of tissue studied, and the methods ofstudying the index. For example, in an extensive study of TLin various tissues, it was determined that in 21 types of tissue,there is a negative correlation of TL with age (the strongestcorrelations for whole blood and gastric tissue), while nocorrelation was observed for testes, ovaries, cerebellum,vagina, skeletal muscle, thyroid gland, and gastroesophagealjunction tissue .When studying long-livers as a model of healthy aging,it was hypothesized that TL primarily depends on thephysiological state of the organism rather than age. It wasshown that in \u201chigh-performing\u201d long-livers , TL wassignificantly higher than TL in \u201clow-performing\u201d long-livers.Therefore, it has been suggested that it is probably not thetelomere length factor that affects the ability to live to onehundred years, but the health condition associated withtelomere length . Thistheory is also supported by a study of TL in same-sex twinsover the age of 70, which noted a clear association betweenblood white cell TL and physical health, including betweentwins . Thus, the study of telomeredynamics in long-lived individuals is of particular importancebecause they may have developed mechanisms that activelypostpone aging and provide effective protection against thenegative effects of aging processes.The current theory of aging suggests that the accumulationof DNA mutations in somatic cells with age leads to a decrease in cell function due tothe inactivation or disruption of important genes . Indeed, it has been shown that the accumulation ofsomatic mutations occurs with age and at a differential rate fordifferent tissues. For example, in human proximal bronchialbasal cells, the rate of mutation accumulation is approximately29 CNVs per cell per year (CNVs/pcpy) ;in prefrontal cortex and hippocampal neurons, it is 16\u201321CNVs/pcpy ; insubcutaneous preadipocytes, it is 18 CNVs/pcpy; in visceraladipose tissue preadipocytes, it is 27 CNVs/pcpy ; in memory T cells, it is approximately 25 CNVs/pcpy;in naive B-lymphocytes, it is approximately 15 CNVs/pcpy;in hematopoietic stem cells and progenitor cells, it isapproximately 16 CNVs/pcpy ; and inspermatogonia, it is approximately 2 CNVs/pcpy .A vivid illustration of the significance of CNVs for lifespanis provided by studies of the rate of mutation accumulationin the crypts of the large intestine in mammals with differentlifespans . While the rate for humans isapproximately 47 CNVs/pcpy, for giraffes at 25\u201335 years oflife, it is approximately 99 CNVs/pcpy; for ferrets at 14 yearsof life, it is approximately 496 CNVs/pcpy; and for mice at2 years of life, it is approximately 796 CNVs/pcpy. Thus, thedependence of lifespan and the rate of mutation accumulationis well established.At the same time, it has been shown that the frequency ofsomatic mutations in humans in old age is much lower thanthat required for the loss of gene function in a significantnumber of cells, indicating an indirect relationship betweenthe indices . In a study of a large sample ofChinese centenarians compared to controls, it was observedthat CNV levels were significantly higher in the sample ofcentenarians than in the control sample, indicating that thefrequency of CNVs does not directly affect the probabilityof living beyond the population norm .On the other hand, a study of centenarians from Italy obtaineddifferent data, observing that centenarians had significantlylower levels of CNVs than controls .Given the contradictory results obtained in these two studies,more research on this issue is needed.Thus, there are reasons to suggest that there is a significantassociation between aging dynamics, life expectancy, healthyaging, the risk of neurodegenerative diseases, and variousquantitative genomic characteristics. 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The results revealed parasitism by the following species: Rickettsia amblyommatis in Amblyomma cajennense s.s., A. cajennense s.l., Amblyomma coelebs, Amblyomma humerale, Amblyomma longirostre, Amblyomma nodosum, Amblyomma scalpturatum, Amblyomma sculptum, and Amblyomma romitii; Rickettsia parkeri in Amblyomma nodosum, Amblyomma ovale, Amblyomma scalpturatum, and Amblyomma triste; Rickettsia rhipicephali in Haemaphysalis juxtakochi; Rickettsia sp. in A. cajennense s.s., A. nodosum, and A. sculptum, and lastly, \u2018Candidatus Rickettsia andeanae\u2019 in Amblyomma parvum and Rhipicephalus microplus. This study expands the body of knowledge about tick parasitism among wild animals, including new data concerning tick-host associations, and provides information about the epidemiology of tick-borne pathogens in the Center-West region of Brazil.Ticks parasitizing 102 wild animals in the states of Mato Grosso and Goi\u00e1s, Brazil were collected between 2015 and 2018. A total of 2338 ticks belonging to four genera ( Ticks (Acari: Argasidae and Ixodidae) are ectoparasitic arthropods of numerous animal species, while humans are accidental hosts, and one of the most important arthropod vectors of infectious diseases around the world . SeveralRickettsia has been classified in the Spotted Fever Group (SFG), the Typhus Group (TG), the Transitional Group (TRG), the Bellii Group (BG), the Canadensis Group (CG), and several other basal groups are small obligate intracellular gram-negative bacteria that infect invertebrate and vertebrate hosts worldwide with transmission related to ectoparasitic arthropods, mainly ticks . Currentl groups .Rickettsia rickettsii, which is responsible for a high mortality rate among infected humans , caused by the bacterium d humans . This zon Brazil in many n domain . Furtherinforest , transmile ticks , has beele ticks , Bahia , where domestic animals and humans also inhabit, considering the importance of ticks and rickettsial diseases for public health, reinforces the need for research focused on this subject. In view of the importance of the tick-host association and research on rickettsial infection in ticks, this investigation focused on the molecular detection of rickettsiae in ticks collected from free-living or captive wild animals in the Central-West region of Brazil.Amblyomma and Haemaphysalis nymphs were identified morphologically as specified by Amblyomma could not be morphologically identified to the species level because there is insufficient literature available, then the larvae were retained as Amblyomma sp. according to Dermacentor was identified morphologically as described by Dermacentor was considered to be D. nitens. Finally, adults of Rhipicephalus linnaei were identified based on Cole\u00e7\u00e3o de Carrapatos da Universidade Federal de Mato Grosso at the Federal University of Mato Grosso, in Cuiab\u00e1, MT, under the following accession numbers: LDPP-UFMT/N.124-127; 129; 133; 135-137; 139-140; 142-144; 148-150; 155; 157-158; 160-163; 165-174; 176-179; 181; 185; 187-188; 190-195; 199-200; 203; 210; 214-217; 220; 224-227; 229; 231-239; 242; 244-247; 255-256; 260-266; 270-277; 283; 287-291; 294; 296-297 and 303-306.Ticks were collected between 2015 and 2018 from free-living and captive wild animals in the states of Mato Grosso (MT) in part of the Amazon, Cerrado, and Pantanal biomes, and Goi\u00e1s (GO) in the Cerrado biome, both located in the Central-West region of Brazil . SamplesgltA) gene common to all Rickettsia species, according to ompA) found only in Rickettsia of the SFG (R. rickettsii DNA) were included in each of these reactions.In the molecular screening for the detection of rickettsial agents, we attempted to choose all tick species identified, which had more than one specimen per host, including the largest number of vertebrate hosts among each order of animals sampled. Therefore, some whole ticks were subjected to DNA extraction using the guanidine isothiocyanate protocol, being placed in a 1.5-mL microtube containing 150 \u00b5L of TE buffer and homogenized by using a sterile pipette tip as described by the SFG . NegativRickettsia amplicons of the expected size were purified using the Illustra GFX PCR DNA and Gel Band Purification Kit and sent for sequencing at the company ACTGene with the same primers used in the cPCR. To evaluate the quality of the sequences, electropherograms were verified with CLC Genomics Workbench software (Qiagen\u00ae). All the sequences obtained were then analyzed using the Basic Local Alignment Search Tool , Amblyomma cajennense s.s. , A. cajennense s.l. ], 394 Amblyomma dissimile , 142 Amblyomma nodosum , 81 Rhipicephalus microplus , 77 Amblyomma scalpturatum , 68 Amblyomma coelebs , 57 Amblyomma dubitatum , 37 Amblyomma rotundatum , 24 Amblyomma romitii , 23 Amblyomma calcaratum , 22 R. linnaei , 19 A. ovale , 17 Amblyomma triste , 11 Amblyomma humerale , 11 Amblyomma oblongoguttatum , 9 Amblyomma longirostre , 6 Amblyomma parvum , 3 Amblyomma naponense , and 4 Haemaphysalis juxtakochi . In addition, one larva of D. nitens was identified, but 93 larvae could not be identified at the species level and were therefore classified as Amblyomma sp. belonging to four genera and at least 21 species: 1239 ticks of the omma sp. .gltA gene. These samples were as follows: Amblyomma spp. (20 larvae), A. cajennense s.s. , A. cajennense s.l. , A. calcaratum , A. coelebs , A. dissimile , A. dubitatum , A. humerale , A. longirostre , A. naponense , A. nodosum , A. oblongoguttatum , A. ovale , A. parvum , A. romitii , A. rotundatum , A. scalpturatum , A. sculptum , A. triste , H. juxtakochi , and R. microplus , as detailed in A total of 650 DNA-extracted random samples were tested individually (430 adults) and in pools (40 pools of 5 nymphs and two pools of 10 larvae) to screen for rickettsial agents by cPCR targeting the rickettsial gltA gene, at least 54 (8.30%) were found to contain rickettsial DNA through the gltA-cPCR , A. coelebs , A. cajennense s.l. , A. humerale , A. longirostre , A. nodosum , A. ovale , A. parvum , A. romitii , A. scalpturatum , A. sculptum , A. triste , H. juxtakochi and R. microplus .Among the 650 DNA-extracted samples from ticks evaluated by cPCR targeting the ltA-cPCR . FurtherA. cajennense s.s. , A. cajennense s.l. , A. coelebs , A. humerale , A. longirostre , A. nodosum , A. scalpturatum , and A. sculptum showed five different haplotypes corresponding to sequences of R. amblyommatis , with a similarity of 99% (487/488 bp) to 100% (440/440 bp - 488/488 bp). Furthermore, partial sequences showed a 100% (447bp - 491bp) match to R. parkeri strains obtained from A. scalpturatum , A. nodosum , A. ovale , and A. triste ticks. Lastly, a partial sequence of the ompA gene 100% (442/442 bp) identical to R. rhipicephali (KX434736) was found in H. juxtakochi , A. nodosum and A. sculptum showed a 100% match (348/348 bp) to other SFG rickettsiae . In addition, we obtained partial gltA sequence 100% (326/326 bp) identical to R. amblyommatis (MH257786) in A. sculptum and A. romitii . Lastly, sequences of the gltA gene found in A. parvum and R. microplus ticks were identical to each other and a 100% match (350/350 bp) to \u2018Candidatus Rickettsia andeanae\u2019 (MG887826), as shown in Molecular screening for rickettsial agents and sequences obtained from ividual) . PartialompA gene of R. amblyommatis, OP823395 and OP823396 of R. parkeri, OP823394 of R. rhipicephali; and OP823399 for partial sequences of the gltA gene of Rickettsia sp., OP823397 of R. amblyommatis, and OP484958 of \u2018Ca. Rickettsia andeanae\u2019.The GenBank nucleotide sequence accession numbers for the partial sequences generated in the present study are: OP823389, OP823390, OP823391, OP823392, and OP823393 for partial sequences of the A. cajennense complex, followed by A. dissimile, A. nodosum, R. microplus, A. scalpturatum, A. coelebs, A. dubitatum, A. rotundatum, A. romitii, A. calcaratum, R. linnaei, A. ovale, A. triste, A. humerale, A. oblongogutattum, A. longirostre, A. parvum, A. naponense, H. juxtakochi, and D. nitens.This study revealed the presence of at least 21 tick species parasitizing wild animals in the states of Mato Grosso and Goi\u00e1s, in the Central-West region of Brazil, between 2015 and 2018. The most abundant species among the collected ticks was the A. dissimile and A. rotundatum ticks , reported to be the main hosts of adult stages of A. nodosum was expesculptum , 2023. Bn Brazil , as repo nodosum . Althougnteaters , this paRhipicephalus microplus is strongly associated with cattle was expected, since this Rickettsia species has been reported in 34 tick species worldwide infecting A. triste. Phylogenetic analysis of R. parkeri indicated the existence of different strains: R. parkeri s.s., R. parkeri strain Atlantic rainforest, R. parkeri strain NOD, and R. parkeri strain Parvitarsum (R. parkeri strain Atlantic rainforest is responsible for mild cases of human rickettsiosis, transmitted mainly by adult A. ovale ticks and occurring widely throughout the Brazilian Atlantic Forest (Finally, molecular analyses revealed the presence of vitarsum . In Brazc Forest .R. parkeri s.s. has also been described infecting A. triste in southeastern and midwestern Brazil (A. tigrinum (A. dubitatum (R. parkeri s.s. has never been confirmed in the laboratory in Brazil, although A. tigrinum in this country.n Brazil , and A. tigrinum and A. dubitatum in the PA. rotundatum parasitizing R. diptycha, adult A. dissimile ticks on E. notaeus and P. palpebrosus, and adult A. sculptum on P. geoffroanus. As for mammals, new associations were described for adults and nymphs of A. cajennense s.s. on M. americana and nymphs on M. tridactyla, larva of D. nitens on C. brachyurus, nymphal stages of A. cajennense s.s. and A. oblongoguttatum on P. concolor and L. pardalis, respectively, and lastly, the occurrence of A. cajennense s.s. nymphs on E. sexcinctus.This paper offers new information on tick-host associations with amphibians and reptiles, including nymphs of R. parkeri, demonstrating the importance of the study in the epidemiological context of One Health.In addition, we have shown a wide diversity of rickettsiae infecting the tick fauna recorded, including a potentially human pathogen species,"} +{"text": "IA (invasive aspergillosis) caused by azole-resistant strains has been associated with higher clinical burden and mortality rates. We review the current epidemiology, diagnostic, and therapeutic strategies of this clinical entity, with a special focus on patients with hematologic malignancies.Aspergillus spp. worldwide, probably due to environmental pressure and the increase of long-term azole prophylaxis and treatment in immunocompromised patients . The therapeutic approaches are challenging, due to multidrug-resistant strains, drug interactions, side effects, and patient-related conditions.There is an increase of azole resistance in Aspergillus spp. strains is fundamental to initiate an appropriate antifungal regimen, above all for allogeneic hematopoietic cell transplantation recipients. Clearly, more studies are needed in order to better understand the resistance mechanisms and optimize the diagnostic methods to identify Aspergillus spp. resistance to the existing antifungal agents/classes. More data on the susceptibility profile of Aspergillus spp. against the new classes of antifungal agents may allow for better treatment options and improved clinical outcomes in the coming years. In the meantime, continuous surveillance studies to monitor the prevalence of environmental and patient prevalence of azole resistance among Aspergillus spp. is absolutely crucial.Rapid recognition of resistant Aspergillus spp. was identified by an Italian priest Micheli in 1729, who named it after the shape of an Aspergillum (sprinkler of holy water) [A. fumigatus, followed by A. flavus, A. terreus, and A. niger. [The mold y water) ,\u00a04. Inva. niger. Prolonge. niger. . In the . niger. ,\u00a09. Amon. niger. , 11Furthermore, patients in the intensive care unit patients or infected with SARS-CoV-2 and patients with advanced liver cirrhosis or under long systemic corticosteroid therapy are also at risk for IA. , 13,\u00a014Aspergillus strains have been associated with therapeutic failure and mortality rates as high as 90% [Aspergillus spp.Considering the increasing number of patient populations at risk for IA, higher numbers of patients are exposed to broad-spectrum azoles, such as voriconazole, posaconazole, or isavuconazole, either as prophylaxis or treatment , 18,\u00a019.h as 90% . In thisA. fumigatus (ARAF) strains caused by the mutations TR34/L98H or TR46/Y121F/T289A have been reported worldwide [A. fumigatus in cystic fibrosis patients, as well as in patients with hematological malignancies, 5.3\u20139 and 1.1\u20131.3%, respectively. [A. fumigatus strains initially, and later in two patients with cystic fibrosis [Azole-resistant orldwide . The firorldwide . Due to orldwide . This coorldwide . The SCAorldwide . The Netorldwide , 28. In orldwide . A Belgiorldwide . In Spaiorldwide , 32. Stuctively. ,\u00a036 Lazzctively. . Similarctively. , 39. In ctively. , 41,\u00a042 ctively. , 44. In fibrosis . Based oA. fumigatus were reported to be azole resistant [In the USA, the first reported TR34/L98H mutation was reported in 2016 . Betweenesistant . In Soutesistant A. fumigatus includes \u201ccryptic\u201d species causing IA, albeit associated with higher mortality rates [A. fumigatus. [A. fumigatus species is A. lentulus, first described in 2004 in allogeneic HCT recipients [A. lentulus represents\u2009<\u20093% of all A. fumigatus spp. in clinical specimens, it could account for 10\u201330% of misidentified/sub-categorized ARAF [A. fumigatus) are probably responsible for the development of azole resistance in A. lentulus. [A. (Neosartorya)udagawae, isolated for the first time in 1995, accounts only for a small percentage of IA cases but, as A. lentulus, is often resistant to voriconazole and amphotericin B [fumigatus include A. viridinutans/felis and A. fischeri/thermomutatus. [The section ty rates . \u201cCryptimigatus. The mostcipients . It is mcipients . Althougzed ARAF , 68. Mutentulus. Since thericin B , 70. Othmutatus. fumigatus species in clinical samples (A. fumigatus accounted for less than 50%) [A. flavus, A. terreus, A. tubigensis, A. niger, and A. nidulans represented 8.4, 8.1, 6.8, 6.5, and 2.5%, respectively, of all clinical samples in this population-based survey [A. flavus (13.3%), followed by A. niger (6.0%) and A. terreus (5.0%) [Aspergillus sections was of 10% and 12% in the two previously cited studies, respectively. [A. flavus is worldwide the second cause of IA after A. fumigatus, with higher prevalence reported in sub- and tropical countries like India, Pakistan, and Sudan [A. flavus (39.4% A. fumigatus) [A. flavus strains [A. terreus accounts for a minority of IA infections, but with a prevalence as high as 30% among IA cases in specific geographical regions such as Houston, Texas (USA) and Innsbruck, Tyrol (Austria) [A. terreus in hematological patients of 4.8% [A. terreus isolates in Germany, 12.5% in the UK, and 10% in Austria, worldwide. A total of 5.4% of all section Terrei isolates were posaconazole-resistant; voriconazole and itraconazole resistance was rare and mostly found in the \u201ccryptic\u201d species of this section such as A. citrinoterreus and A. alabamensis. [A. terreus, considering the amphotericin-B resistance, which is likely related to drug uptake reduction and higher catalase activity [A. citrinoterreus is reported to be the most common \u00ab\u00a0cryptic\u00bb species in the section Terreus (8.4%), followed by A. hortai (2.6%) and A. alabamensis (1.6%) [A. niger is considered to be of lower virulence in comparison to other Aspergillus spp. with incidence in transplant recipients between 0.048 and 0.16%, as reported by the TRANSNET group [A. niger complex over a 7-year period [A. tubingensis was responsible for 5 of these cases [A. tubingensis as A. awamori/welwitschiaceae is known to have higher triazole MICs limiting the available treatment options [A. ustus with the \u201ccryptic\u201d species A. calidoustus and A. pseudodeflectus are rare causes of IA, with a recent literature review showing 67 reported cases of probable/proven IA worldwide due to A. ustus complex [A. nidulans with the \u201ccryptic\u201dspecies A. sublatus, A. quadrilineatus is a very rare cause of IA, described mostly in patients with the chronic granulomatous disease , observed in osteomyelitis and in patients receiving itraconazole prophylaxis [A. nidulans. [A large Spanish study showed a high prevalence of non-han 50%) . Overalld survey . On the s (5.0%) . The prectively. , 71 A. fnd Sudan , 74,\u00a075. strains . A. terrAustria) , 77. Rec of 4.8% . Posaconamensis. Since thactivity . A. citrs (1.6%) . Azole rs (1.6%) A. nigerET group , 81. A Br period . The \u201ccrse cases . A. tubi options . A. ustu complex . Half of complex , 85. Sin complex . Also, Aphylaxis , 87,\u00a088.A. fumigatus, and data are missing for other species. More studies are needed, considering the important clinical burden of these infections [A. flavus. [A. lentulus azole-resistance [A. fumigatus cyp51A or other type of mutations in different genes could possibly induce an overexpression of cyp51, which increases the azole concentrations needed to inhibit fungal growth (since azoles are binding to cyp51 protein in order to block the formation of ergosterol) [The pathogenesis of azole resistance is complex and multi-factorial. Moreover, most of the studies have been conducted in fections . First, fections , 91,\u00a092.fections . For ins flavus. , 94 Furtsistance . Second,osterol) , 96,\u00a097.osterol) ,\u00a098. Sucosterol) . Finallyosterol) , 101. Otosterol) A. fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus, while CLSI has proposed only voriconazole CBPs for A. fumigatus. [The diagnosis of azole resistance is based on the phenotypic measurement of MIC, which is the threshold to differentiate a resistant from a susceptible strain. MICs are used together with pharmacokinetic/pharmacodynamic (PK/PD) data to determine the clinical breakpoints (CBPs), which are susceptibility predictors ,\u00a0105. Thmigatus. . Overallmigatus. . Other cmigatus. A. fumigatus-related mutations [A. fumigatus and could be used for different other species. Due to high costs, long turn-around time, and high-level expertise needed, its utility remains very limited. [Genotypic testing for azole resistance is based mostly on PCR methods, targeting directly the most frequent point mutations in the cyp51A gene and its promoter and the tandem repeat insertions , 108. Cuutations . MALDI-Tutations . Eventualimited. The incidence of IA in patients with acute myeloid leukemia or allogeneic HCT recipients has ranged between 5 and 15%. , 114Aspergillus spp. present clinically similar to patients infected with non-resistant strains, usually with a pulmonary infection, followed by sinusonasal and cerebral IA [Aspergillus spp. in IA showed a 21\u201331% higher mortality in the azole resistant group [Aspergillus spp. should be rapidly raised in the context of a lack of clinical and biological response to the administered therapy.Allogeneic HCT recipients with IA due to azole-resistant ebral IA . Rapid debral IA ,\u00a0118. Cont group , 119. Asnt group , 121. ClAspergillus strains, there are no controlled clinical trial data; hence treatment recommendations are based mostly on expert opinion [MIC\u2009>\u20092\u00a0mg/ml) IA amphotericin-B lipid formulation monotherapy or a combination of voriconazole or isavuconazole with an echinocandin [The cornerstone of IA treatment is broad-spectrum triazoles, including voriconazole, isavuconazole, and posaconazole ,\u00a0125. Di opinion . Latest opinion ,\u00a0129. Ho opinion . The rignocandin . Even ifnocandin ,\u00a0132A. fumigatus, such as A. udagawae, A. thermomutatus, and A. lentulus, show high MICs for all azole drugs, and A. lentulus and A. udagawae have higher MICs also for amphotericine-B products [A. lentulus and A. udagawae, although data are very limited. [As mentioned above, resistance testing may not always be feasible, because of the lack of culture growth and isolation difficulties for cryptic species in specific patient subgroups. In these cases, diagnosis of possible resistance is predominately based on clinical suspicion and treatment should always be discussed with the local infectious disease team. The \u201ccryptic\u201d species for the section products , 134. Islimited. fumigatus Aspergillus spp., voriconazole is the first-line therapy for A. flavus. [A. terreus and his \u201ccryptic\u201d species, voriconazole and itraconazole are the preferred antifungal molecules [A. niger section (example given A. tubigensis) are often resistant to the triazoles; for this reason, liposomal amphotericine B is preferred [A. ustus is still not elucidated due to the absence of clinical trials. ESCMID recommend the use of amphotericin-B products, since often these infections are breakthrough IA under posaconazole or voriconazole prophylaxis [Concerning the therapy for non- flavus. Echinoca flavus. . Since polecules , 135. Lireferred . The optphylaxis . Isavucophylaxis A. calidoustus and A. terreus, if used in combination with liposomal amphotericin-B or azole [Aspergillus spp. in animal models [Aspergillus spp., the thus far reported MIC data of some of them suggest that they may represent an important tool in the management of those infections.New antifungal molecules could play a role in the treatment of azole-resistant IA in the future. For example, ibrexagungerp shows an activity against azole-resistant isolates of or azole . Rezafunl models . FosmanoAspergillus spp. strains is fundamental to initiate an appropriate antifungal regimen in allogeneic HCT recipients and patients with hematologic malignancies. Clearly, more studies are needed in order to better understand the resistance mechanisms and to optimize the diagnostic methods to identify Aspergillus spp. resistance to the existing antifungal agents/classes. Currently, therapeutic approaches are challenging, due to multidrug-resistance strains, drug interactions, side effects, and patient-related conditions. More data on the susceptibility profile of Aspergillus spp. against the new classes of antifungal agents, which are in phase I\u2013III clinical trials, may allow for better treatment options and improved clinical outcomes in the coming years. In the meantime, continuous surveillance studies to monitor the prevalence of environmental and patient prevalence of azole resistance among Aspergillus spp. is absolutely crucial.There is an increase in azole resistance worldwide probably due to environmental phenomena (massive use of azole-containing fungicide in agriculture) and due to the increase of long-term azole prophylaxis and treatment in immunocompromised patients. IA caused by those strains has been associated with higher clinical burden and mortality rates. Rapid recognition of resistant"} +{"text": "A 26-month-old boy presented with recurrent hematochezia. Abdominal examination was normal. Laboratory findings showed hemoglobin of 7.5\u2009g/dL. Abdominal ultrasound (US) for intussusception revealed a short (0.3\u2009cm) segment of wall thickening in the distal ileum and Meckel\u2019s scan was negative. The patient underwent two additional Meckel\u2019s scans, tagged red blood cell scan, CT-angiography, upper endoscopy and colonoscopy, and video capsule endoscopy, but had normal results. Superior mesenteric angiography was performed revealing an area of abnormal vasculature in the terminal ileum Fig. . SubsequMD is the most common congenital malformation of the gastrointestinal tract, occurring in approximately 2% of the population . The golA.P. was involved in conception and design, acquisition of data, drafting the work, final approval of the version to be published. M.R.A., P.M., T.R.B., and C.M.S. were involved in conception and design, critical revision of work, final approval of version to be published. L.A. was involved in conception and design, acquisition of data, critical revision of work, final approval of version to be published."} +{"text": "Bacterial species of the genus Rhodococcus are known to be efficient degraders of hydrocarbons in contaminated soil. They are also employed for bioremediation of polluted environments. These bacteria are widely met in soil, water and living organisms. Previously, we have isolated the Rhodococcus qingshengii strain VKM Ac-2784D from the rhizosphere of couch grass growing on oil-contaminated soil. This strain can effectively degrade oil and some model compounds . The results of phylogenetic analysis show that this strain belongs to the species R. qingshengii. To understand the catabolic properties of this strain, we have studied its gene clusters possessing such properties. The alkane destruction genes are represented by two clusters and five separate alkB genes. The destruction of aromatic compounds involves two stages, namely central and peripheral. The R. qingshengii VKM Ac-2784D genome contains four out of eight known central metabolic pathways for the destruction of aromatic compounds. The structure of the gene clusters is similar to that of the known strains R. jostii RHA1 and R. ruber Chol-4. The peripheral pathways include the genes encoding proteins for benzoic acid destruction. The presence of biphenyl 2,3-dioxygeneses as well as gene clusters of benzoate and 2-hydroxypentandienoate pathways suggests that R. qingshengii VKM Ac-2784D could degrade polychlorinated biphenyls. The biodegradation ability can be enhanced by biosurfactants, which are known to be synthesized by Rhodococcus. The R. qingshengii VKM Ac-2784D genome contains the otsA, otsB, treY, treZ genes. The bioinformatics data are supported by the previous biochemical experiments that allow a mixture of species with a wide variation of metabolic pathways to be obtained. Rhodococcus is a genus of Gram-positive bacteria of theActinobacteriaphylum, which are widespread in nature.These bacteria have been isolated from soil, water and livingorganisms.Some species of Rhodococcus are known tobe pathogens, e. g. R. hoagii (former R. equi), which causeszoonotic infection, and R. fascians phytopathogen .Over the last decade, rhodococci have attracted considerableinterest owing to their high catabolic properties. Thesebacteria are able to degrade various pollutants and, therefore, can be employed for bioremediationof soils .The application of rhodococci in bioactive mixtures requiresan understanding of which pollutants are capable ofdestroying a microorganism. This goal can be achieved bythe joint use of bioinformatic and biochemical approaches.Currently, most of the genes and pathways of pollutants degradationare known.To date, numerous gene clusters of rhodococci genomes,which encode oil-degrading enzymes, have been reported. The key components of alkanedegradation are alkane-monooxigenase and cytochrome . Enzymes AlkB and CYP153are usually involved in the oxidation of liquid alkanes, whileSDIMO exerts an action on short-chain alkanes (A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype. One of the most common congenital metabolic disordersis familial hypercholesterolemia (FH) .Familial hypercholesterolemia is a condition caused by atype of genetic defects leading to a decreased rate of removalof low-density lipoproteins from the bloodstream anda pronounced increase in the blood level of total cholesterol. This illness leads to early developmentof cardiovascular diseases of atherosclerotic origin . Familialhypercholesterolemia is a monogenic disease with predominantlyautosomal dominant inheritance .The prevalence of the heterozygous type of FH in white populationsis 1 per 250 people . Rare pathogenicvariants in the LDLR gene are present in 75\u201385 % ofcases with an identified molecular genetic cause of the disease,and variants in other genes occur in this group of patientswith a frequency of less than 5 % . Patients can behomozygous or heterozygous carriers of pathogenic variants,and this status determines the severity of the disease and onsetage of manifestations of cardiovascular complications . A negative result of genetic screening for pathogenicvariants does not rule out familial hypercholesterolemia.In 20\u201340 % of cases, changes in the above genes are absentaccording to molecular genetic analysis. The risk of coronaryheart disease among patients with FH is 20 times higher inthe absence of treatment ; therefore, itis important and relevant to search for new approaches toidentifying patients at early disease stages and to assessingpredisposition to this disease in patients\u2019 familiesTo search for new cases, some authors have proposed aclassifier to identify potential patients with FH by means ofelectronic medical records. Using data from patients withconfirmed FH (n = 197) and cases without FH (n = 6590), adecision tree classifier was trained in that study. The classifiershowed a positive predictive value (PPV) of 0.88 and a sensitivityof 0.75 for long-term testing. This classifier proved to beeffective at finding candidate patients for further screening forfamilial hypercholesterolemia. Such machine-learning-basedstrategies can result in efficient identification of patients havingthe highest risk of the disease .For the diagnosis of FH, clinicians use the principle ofcascade genetic screening. The latter is a step-by-step identificationof patients with familial hypercholesterolemia. Whenelevated blood levels of total cholesterol and low-densitylipoprotein cholesterol (LDL-C) are detected in a patient,his/her family history of health problems is collected andclinical manifestations are analyzed. In case of a diagnosisof \u201cprobable\u201d or \u201cdefinite\u201d FH according to the Dutch LipidClinic Network Criteria ,the patient is referred for molecular genetic testing.The cascade screening includes quantitation of blood lipidsin all first-degree relatives of the proband. If the FH diagnosisis confirmed by the molecular genetic methods, then geneticscreening is performed on his/her relatives. As new patientswith FH are identified, their relatives are examined too.The cascade screening is the most effective way to detectpreviously undiagnosed FH The aim of the present work was to search for new genesassociated with the FH phenotype using modern high-techmethods of sequencing and machine learning.A group of patients with FH ,was recruited from a clinical diagnostic department at the Instituteof Internal and Preventive Medicine (IIPM) \u2013 a branchof the Institute of Cytology and Genetics, the Siberian Branchof the Russian Academy of Sciences (ICG SB RAS). The studyprotocol was approved by the Ethics Committee at the IIPM \u2013 abranch of the ICG SB RAS, decision No. 68 of June 4, 2019.Informed consent was obtained from each study participant.The diagnosis of FH was made in accordance with the clinicallipid criteria of the Dutch Lipid Clinic Network (DLCN). According to thecriteria, a score was computed (see the Supplementary)1 forpatients with familial hypercholesterolemia. The patients underwenta medical examination, ultrasonographic diagnostics,and blood sampling for biochemical assays and moleculargenetic assays.http://vavilov.elpub.ru/jour/manager/files/Suppl_Ivanoshchuk_Engl_27_5.pdfSupplementary Materials are available in the online version of the paper:Blood samples for the biochemical analyses were collectedonce from the cubital vein in the morning on an empty stomachat 12 h after a meal. Serum levels of total cholesterol,triglycerides, LDL-C, high-density lipoprotein cholesterol(HDL-C), and glucose were determined by enzymatic methodson a KoneLab300i automatic biochemical analyzer (Finland)with reagents from TermoFisher (Finland). The LDL-C levelwas calculated via the Friedewald formula; at the LDL-Cconcentration of > 4.5 mmol/L, the method of direct quantificationof LDL-C was used. Statistical analysis of the data wasperformed in the SPSS software for Windows, version 23.0.Phenol-chloroform extraction was carried out to isolateDNA from blood . The quality ofthe extracted DNA was assessed with the help of an Agilent2100 Bioanalyzer capillary electrophoresis system .Targeted DNA sequencing in patients with FH was performedon the MiSeq platform (Illumina) using a customdesignedpanel of 43 genes: LDLR, APOB, PCSK9, LDLRAP1,CETP, LPL, HMGCR, NPC1L1, PPARA, MTTP, LMF1,SAR1B, ABCA1, ABCG5, ABCG8, CYP7A1, STAP1, LIPA,PNPLA5, APOA1, APOA5, APOC2, APOE, LCAT, ANGPTL3,LIPC, APOA4, APOC3, SREBF1, LMNA, PPARG, PLIN1,POLD1, LPA, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5,SMAD6, SMAD7, SMAD9, and LIPG .At the next stage of this work, from the study population,42 patients with FH were chosen who did not show pathogenicvariants in the tested genes during the targeted sequencinganalysis. These patients were subjected to multiplex ligationdependentprobe amplification (MLPA) analysis to identifypossible sequence alterations (deletions or duplications) in theLDLR gene promoter and exons by means of SALSA MLPAKIT P062 .Using the group of patients with FH , decision trees wereconstructed, which enabled us to identify cases in this groupthat require additional molecular genetic analysis. Softwarewas written in Python 3.9 for building a set of decision rulesfor predicting FH on the basis of machine learning with alimited training set. The decision rules were stored as datarepresentation in the Predictive Model Markup Language.The decision rules were built by means of a labeled databaseof patients with a diagnosis of FH .By machine learning methods, five probands with the severestFH without pathogenic variants in the tested genes were identified for subsequent whole-genome sequencing on theHiSeq 1500 platform (Illumina). Automated processing andannotation of the obtained sequencing data were conductedon the NGS Wizard platform . The sequencereads were mapped to the reference human genome (GRCh38/hg38). A potential effect of novel missense variants on proteinfunction/structure was assessed using data from in silicoprediction tools (CADD (https://cadd.gs.washington.edu/snv),PolyPhen2 (http://genetics.bwh.harvard.edu/pph2/), and MutationTaster(https://www.mutationtaster.org/)) and data fromgnomAD on the frequency of these variants in populations. Inthis way, variants (in genes associated with lipid metabolism)leading to a loss of protein function and missense variants witha frequency of less than 0.01 % were selected. Pathogenicityof new variants was evaluated according to the guidelines ofthe American College of Medical Genetics and Genomics(ACMG) and the Association for Molecular Pathology. Analysis of protein-protein interactionnetworks was performed in STRING .By targeted sequencing and MLPA, \u201cpathogenic\u201d and \u201clikelypathogenic\u201d variants were detected in 47.5 % of the examinedprobands and in 85.7 % of the probands\u2019 children. Variantsin the LDLR gene that were identified in patients with the FHphenotype in our study are presented in Table 1. All missensevariants were found to be in a heterozygous state. VariantsCys352Tyr, Cys340Phe, and Leu401His have been previouslydescribed in patients with FH in Russia and in other countries .In the study population, the heterozygous type of thedisease was due to rare variants in the LDLR gene in 73 %of the cases. Two new variants \u2013 NM_000527.5:c.266G>C,NP_000518.1:p.Cys89Ser and NM_000527.5:c.1123T>G,NP_000518.1:p.Tyr375Asp \u2013 were identified in the LDLRgene. Two unrelated probands turned out to be carriersof compound heterozygous variants of the LDLR gene,whereas the clinical course of the disease in these patientscorresponded to the homozygous type of familial hypercholesterolemia.In the first case, in a 28-year-old female patientwith a diagnosis of definite FH, we detected rare variantsNM_000527.5:c.796G>A, NP_000518.1:p.Asp266Asn, andNM_000527.5:c.1054T>A, NP_000518.1:p.Cys352Ser inexons 5 and 7 of LDLR (see Table 1). In the second case, a35-year-old female patient with a diagnosis of definite FH hastwo missense variants in exons 3 and 8 of LDLR. One substitutionis located in LDLR exon 3 , in which at this position, rare likelypathogenic variant rs875989894 NM_000527.5:c.266G>A,NP_000518.1:p.Cys89Tyr has been previously describedin patients with FH .The pathogenicity of the identified variant was confirmedby in silico analysis . The other new missense variantis situated in exon 8 of LDLR: NM_000527.5:c.1123T>G,NP_000518.1:p.Tyr375Asp (see Table 1). This missensevariant causes an amino acid substitution at the same positionwhere other missense variants have been described before as likely pathogenic in patients with FH . The pathogenicity of the variant was also confirmedby in silico analysis . Both detected variants arenot annotated in the gnomAD database (v2.1.1). Accordingto this evidence, both were assumed to be likely pathogenicvariants.Patients without functionally significant substitutions inlipid metabolism genes were analyzed by MLPA to determinesequence changes (deletions or duplications) in the promoterand exons of the LDLR gene. This assay revealed a deletionof a coding region in the LDLR gene [NM_000527.4:c.(2140+1_2141-1)_(2311+1_2312-1)del] in DNA samplesfrom two unrelated patients.In the molecular genetic analysis, in three patients fromtwo unrelated families (a proband and a son of the probandfrom one family and a proband from another family), weidentified variant rs5742904 (ClinVar Variation ID:17890)in the APOB gene (see Table 1).Rare substitutions in the APOB gene region encoding theLDL receptor-inding site are associated with hypercholesterolemia.One of the variants in this region, NP_000375.3:p.Arg3527Gln, leads to hypercholesterolemia with reducedclearance of LDL-C owing to a defect in the structural motifof LDL that is responsible for affinity for LDL receptor .Analysis of our data of targeted high-throughput sequencingrevealed rare pathogenic variant rs118204077 inthe LPL gene in a heterozygous state (ClinVar Variation ID:1548) (see Table 1). This variant was found in a 45-year-oldmale patient with hypercholesterolemia (12.4 mmol/L) andhypertriglyceridemia . Earlier,variants associated with hypertriglyceridemia have been describedat this locus in patients with lipoprotein lipase deficiency .According to the results of the molecular genetic analyses,52.5 % of our patients are not carriers of pathogenic variants inthe studied lipid metabolism genes. Among these patients, bya machine learning algorithm, five subjects with the severestFH were chosen for whole-genome sequencing. As a result,in three patients, four variants with a minor allele frequencyof less than 0.01 % were identified in genes related to lipidmetabolism. Among these variants, two are single-nucleotidedeletions, one affects a splicing acceptor site, and one is a missensevariant. The findings are presented in Table 2.In the SIDT1 gene , a new previously undescribedvariant was detected that yields a frameshift starting with codon 809 . The gene consists of 30 exons and is locatedin chromosomal region 3q13.2 (https://www.ncbi.nlm.nih.gov/gene/54847). According to gnomAD, loss-of-functionvariants in this gene have been documented, but according toClinVar and the literature, none of them have been annotatedas pathogenic or likely pathogenic. For this gene, the pLI scorewas found to be 0, indicating that the gene is resistant to lossof-function variants. The weight of evidence suggested thatthis variant has uncertain clinical significance (pathogenicitycriterion PM2)A new missense variant was found in the LRP1B gene (LDLreceptor-related protein 1B): c.10313C>G p.Pro3438Arg in aheterozygous state. The gene is located in chromosomal region2q22.1-q22.2, consists of 92 exons, and encodes one of thereceptors of the LDL receptor family (https://www.ncbi.nlm.nih.gov/gene/53353). In gnomAD, there are no data on thefrequency of this variant. The pathogenicity of this variantwas also corroborated by in silico analysis . Mostvariants in this gene either are benign or have uncertain clinical significance.The totality of the data indicated that this variant hasuncertain clinical significance .One of our patients proved to be a carrier of a rare heterozygousvariant at a splicing acceptor site in the phospholipase D1 (PLD1) gene. This variantis registered in a control sample in gnomAD: five mutant alleleson 282,768 chromosomes (no homozygotes have beendetected). The PLD1 gene codes for a phosphatidylcholinespecificphospholipase that catalyzes the hydrolysis of phosphatidylcholine,thus yielding phosphatidic acid and choline(https://www.ncbi.nlm.nih.gov/gene/5337). The gene is situatedin chromosomal region 3q26.31 and contains 35 exons.Phospholipase D (PLD) and its enzymatic reaction product,phosphatidic acid, regulate adhesion of immune cells (macrophagesand neutrophils) to collagen .It is known that biallelic variants with loss of function ofthe PLD1 gene cause neonatal cardiomyopathy and congenitalmalformations of the pulmonary valve and tricuspid valve, ofthe right ventricle of the heart, and of the outflow tract of theright ventricle .The weight of evidence suggested that this substitution is alikely pathogenic variant in relation to congenital heart malformations(pathogenicity criteria PM2 and PVS1). Withrespect to FH, we categorized the detected substitution asa variant of unknown clinical significance (pathogenicitycriterion PM2).One of the examined patients was found to have a heterozygoussingle-nucleotide deletion in CETP: rs753876598(NM_000078.3:c.165del) (https://www.ncbi.nlm.nih.gov/gene/1071). The variant is annotated in the ClinVar database(ID1675625) and is registered in a control sample of gnomAD:four mutant alleles on 282,774 chromosomes (no homozygoteshave been found). It is known that variants causing loss offunction of this gene affect the HDL-C level . According to the totality of criteriafor pathogenicity evaluation (PM2 and PVS1), we designatedthis variant as likely pathogenic. The CETP gene codes fora plasma protein that catalyzes the exchange of triglyceridesand cholesterol esters between lipoprotein particles .High-throughput sequencing is employed not only for moleculargenetic diagnosis of FH but also as a tool for identifyingi) variants that may be involved in lipid metabolism and ii)their effects on the phenotype of patients with FH . In the current study, 16 variants wereidentified in an FH population (15 single-nucleotide substitu-tions and one deletion) that have previously been classifiedas pathogenic or likely pathogenic in the ClinVar or LOVDdatabase as well as two new missense variants in the LDLRgene that we classified as pathogenic. In our genome-wideanalysis, in lipid metabolism-associated genes, we detectedfour additional variants that met our search criteria. Twoof these four variants have been described before, and twoare new.One of the genes in which rare variants were found inpatients with FH is PLD1, encoding phospholipase D1. Thisenzyme hydrolyzes membrane lipid phosphatidylcholinethereby generating phosphatidic acid .Phosphatidic acid is an intermediate metabolite in the synthesisof all membrane glycerophospholipids and plays animportant structural role in live cells by promoting membrane biogenesis ; furthermore, its involvementand phospholipase D1\u2019s participation in exocytosis have beendemonstrated .Alternative splicing of PLD1 mRNA results in manydifferent transcripts having both catalytic and regulatoryfunctions . It has been shown thatrecessive variants in the PLD1 gene are associated with severeright-sided congenital heart malformations in two families. In Pld1 knockout mice, moderatedysfunction of pulmonary and tricuspid valves is observed. Recessive PLD1 variants also correlatewith isolated neonatal cardiomyopathies . In humans, missense variants of PLD1 are reported tobe concentrated in regions of the protein critical for catalyticactivity, thus resulting in low enzymatic activity in most ofsuch mutant proteins . It has also beendemonstrated in cell lines that PLD1 overexpression promotesthe formation of lipid droplets, whereas an siRNA PLD1knockdown inhibits this process .The variant that wedetected in a proband with FH without signs of congenitalheart disease is in a heterozygous state. Considering the lowprevalence of this variant and its possible role in subcellulartransport and in the formation of lipid droplets, this substitutionis of interest for further investigation in individuals withlipid metabolism disorders.Another rare variant was found by us in the LRP1B gene(LDL receptor-related protein 1B). The LRP1B protein is amember of the LDL receptor family .LRP1B takes part in lipoprotein catabolism; accordingly,research on rare variants of the LRP1B gene in individualswith FH is promising. Most of the recently identified ligandsof LRP1B are well-known factors of blood coagulation and oflipoprotein metabolism, suggesting that LRP1B is implicatedin atherosclerosis .SIDT1 is a multispan transmembrane protein belonging tothe SID1 transmembrane family and shares some sequencehomology with Caenorhabditis elegans ChUP-1, which is acholesterol-binding protein located in intracellular vesicles. SIDT1 expression in endolysosomeshas been documented . SIDT1 has beenshown to participate in cholesterol transport but has not been investigated in the context ofthe FH phenotype. Most likely, the variant that we found inthis gene does not take part in the formation of the clinicalphenotype of FH because our assessment using the AmericanCollege of Medical Genetics and Genomics criteria classifiesit as a variant of uncertain clinical significance; however, forunambiguous evaluation of its association with the FH phenotype,additional data are needed.The CETP gene codes for the CETP protein, which carriescholesterol esters. This protein regulates the concentration andparticle size of HDL-C in the blood and plays an importantrole in reverse cholesterol transport .It has been shown that elevated activity of CETP reducesHDL-C concentration and correlates with a higher risk ofcardiovascular disease .Variants in the CETP gene can alter the blood lipid profile. In our previous study on one of the CETPvariants, we reported its association with changes in the bloodlipid profile and with the risk of myocardial infarction in apopulation of Western Siberia . When amap of functional and physical associations was constructedin the present study, the APOB protein turned out to be a predictedfunctional partner of the CETP protein, and mutationsin APOB represent some of FH etiologies.Additional segregational and functional analyses are necessaryto evaluate pathogenic effects of the identified variantson the formation of the clinical FH phenotype. Identificationof new pathogenic variants will facilitate risk assessment ofFH and of its complications among patients and members oftheir families.A combination of machine learning and whole-genome sequencingin probands with a clinical diagnosis of FH revealedrare variants in genes SIDT1, LRP1B, PLD1, and CETP; thesevariants may influence the disease phenotype.The authors declare no conflict of interest.Andersson L., Bostr\u00f6m P., Ericson J., Rutberg M., Magnusson B.,Marchesan D., Ruiz M., Asp L., Huang P., Frohman M.A., Bor\u00e9n J.,Olofsson S.O. 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DOI 10.1371/journal.pone.0033962.Vasilyev V., Zakharova F., Bogoslovskaya T., Mandelshtam M. Familialhypercholesterolemia in Russia: three decades of genetic studies.Front. Genet. 2020;11:550591. DOI 10.3389/fgene.2020.550591.Wiegman A., Gidding S.S., Watts G.F., Chapman M.J., Ginsberg H.N.,Cuchel M., Ose L., \u2026 Santos R.D., Stalenhoef A.F., Steinhagen-Thiessen E., Stroes E.S., Taskinen M.R., Tybj\u00e6rg-Hansen A., WiklundO., European Atherosclerosis Society Consensus Panel. Familialhypercholesterolaemia in children and adolescents: gainingdecades of life by optimizing detection and treatment. Eur. Heart J.2015;36(36):2425-2437. DOI 10.1093/eurheartj/ehv157.World Health Organization-Human genetics DoNDP. Familial hypercholesterolaemia:report of a second World Health Organizationconsultation, Geneva: WHO; 1999. URL: https://apps.who.int/iris/handle/10665/66346 (Application: 14.11.2022).Wuni R., Kuhnle G.G.C., Wynn-Jones A.A., Vimaleswaran K.S. A nutrigeneticupdate on CETP gene-diet interactions on lipid-related outcomes.Curr. Atheroscler. Rep. 2022;24(2):119-132. DOI 10.1007/s11883-022-00987-y.Zakharova F.M., Damgaard D., Mandelshtam M.Y., Golubkov V.I.,Nissen P.H., Nilsen G.G., Stenderup A., Lipovetsky B.M., KonstantinovV.O., Denisenko A.D., Vasilyev V.B., Faergeman O. Familialhypercholesterolemia in St.-Petersburg: the known and novel mutationsfound in the low density lipoprotein receptor gene in Russia.BMC Med. Genet. 2005;6:6. DOI 10.1186/1471-2350-6-6."} +{"text": "In the original publication , there wAuthor Contributions: Conceptualization, K.D. and T.L.; investigation, K.D. (reviewed 78 articles), K.E. (reviewed 7 articles) and T.L.; methodology, K.D.; visualization, K.D.; supervision, T.L.; writing\u2014original draft, K.D. and K.E. (Sections 4.2.2 and 5); writing\u2014review and editing, K.D., K.E., T.L. and C.L. All authors have read and agreed to the published version of the manuscript.Khang Dang was not included as an author in the original publication. The corrected Author Contributions statement appears here.The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Epilobium\u00a0angustifolium extracts. A literature search of Scopus, PubMed/Medline, and Google Scholar for peer-reviewed articles published between January 2000 and June 2023 was undertaken. A total of 23 studies were eligible for inclusion in this review. Significant variation of antimicrobial activity depending on the tested species and strains, type of extract solvent, or plant organs utilized for the extract preparation was found. E. angustifolium extracts were active against both Gram-positive and Gram-negative bacteria and showed antimycotic effects against the fungi of Microsporum canis and Trichophyton tonsurans and the dermatophytes Arthroderma spp. Greater susceptibility of Gram-positive than Gram-negative bacteria to fireweed extracts was found. A strong antibacterial effect was recorded for Staphylococcus aureus, Bacillus cereus, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii including multi-drug resistant strains. E. angustifolium extract might find practical application as an antimicrobial in wound healing, components of cosmetic products for human and animals, or as food preservatives.The aim of this work was to provide an overview of available information on the antibacterial and antifungal properties of Epilobium angustifolium and related species have been studied intensively [Recently, the expansion of drug-resistant pathogens has created demand for novel antimicrobials and stimulated the search for natural plant-based compounds as alternatives to synthetics ,2,3. Plaensively ,5,6,7,8.Epilobium angustifolium L. (fireweed or rosebay willow herb) is a well-known medicinal plant from the Onagraceae family (Epilobii angustifolii herba (herb) is often used as a component of nutraceuticals, diet supplements, and cosmetic products. Herb and extracts are commercially available for various indications including BPH, skin irritations, gastrointestinal disorders, or even prostate cancer [E. angustifolium and E. parviflorum stated that herbs of these species meet the requirements for \u201ctraditional use\u201d as teas and infusions with indications for lower urinary tract symptoms related to BPH [E. angustifolium in treatment of BPH has not been sufficiently proven. To date, only one clinical trial has been published [E. angustifolium extract. It should be stressed that a number of preclinical studies have documented anti-cancer [E. angustifolium extracts. Analgesics [e family . The spee cancer . The EMEd to BPH . Efficacublished . The resi-cancer ,13,14, ai-cancer ,16, antii-cancer ,19,20,21i-cancer ,23,24, ai-cancer ,26,27 pralgesics , antichoalgesics . Recentlalgesics and cosmalgesics ,32,33.E. angustifolium extracts results from their complex and diverse chemical composition. More than 250 compounds have been identified, including: ellagitannins (hydrolysable tannins), flavonoids, phenolic acids, lignans, steroids, triterpenoids, fatty acids, essential oil, and alkaloids [E. angustifolium were attributed to the synergic interactions of polyphenols and the high concentration of oenothein B\u2014a macrocyclic (dimer) ellagitannin. Therefore, oenothein B and quercetin-3-O-glucuronide (flavonoid) have been proposed as marker compounds for standardization of the raw material [E. angustifolium plants [The wide spectrum of biological activity of lkaloids . Medicinmaterial . Oenothematerial ,36,37,38material ,40,41. Am plants . Tanninsm plants . SeveralE. angustifolium herb. Flavonoids usually represent about 1\u20132% of the dry mass of plants, but in the mountains, their concentration can be higher, up to 4% [O-glucuronide is a dominant compound [O-rhamnoside and a new compound, 1-(5-(hydroxymethyl) furan-2-yl)-6-methoxyisochroman-7-ol, have been identified as the most active contributors of anti-inflammatory activity of this species [Diverse flavonoids, particularly flavonol aglycones\u2014quercetin, kaempferol, and myricetin\u2014were identified in up to 4% . Among fcompound ,46,47. Tcompound . Flowers species .E. angustifolium extracts. Gallic, caffeic, ellagic, ferulic, and protocatechuic acids as well as caffeoylquinic acid isomers and others have been found [Phenolic acids are significant components of therapeutic activity of en found ,37. Gallen found ,26. Phenen found ,49. TherE. angustifolium has not been thoroughly studied, but antioxidant, antibacterial, and antimycotic properties have been documented [\u03b2-sitosterol, cholesterol, and their derivatives) have also been identified [Essential oil constituents are known for their antimicrobial activity. The biological activity of the essential oil of cumented ,51,52. Oentified ,53,54E. angustifolium extracts have been tested in the treatment of BPH, in wound healing or as ingredients of cosmetic products, nano-bactericides [To date, ericides , and as ericides . AntimicE. angustifolium extracts. This work reviews the current state of knowledge and discusses antimicrobial activity and the relationship between the phytochemical composition of extracts.The aim of this study was to provide an overview of available information on the antibacterial and antifungal properties of E. angustifolium antibacterial and antifungal activity is scarce. Usually, fireweed among other rich-polyphenol species was tested to determine antimicrobial activity . The literature on activity . The gataporator , by maceaporator , by evapaporator , or by uaporator . Phytochaporator ,74,75,76E. coli, S. aureus, P. aeruginosa, and C. albicans were the most often tested. Standard strains, MDR [Chromobacterium violaceum [E. angustifolium extracts are summarized in Different methods and assays such as the disc diffusion test, well diffusion method, cylinder diffusion method, broth dilution method, or quorum sensing assay were appins, MDR ,64, and ins, MDR ,59,62,63iolaceum . The effiolaceum ,75. The S. aureus, E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa strains treated with nanoparticles synthesized with aqueous extract of E. angustifolium [B. cereus [E. coli [P. aeruginosa [K. pneumoniae [E. coli (from 0.625 \u00b5g/mL to 16.2 mg/mL), S. aureus (from 0.625 \u00b5g/mL to 7.6 mg/mL), and P. aeruginosa (from 1.25 \u00b5g/mL to 9.1 mg/mL). Regarding the disc diffusion method, the best bactericidal effect (>20 mm) was recorded for B. cereus [S. aureus [E. coli [K. pneumoniae, and P. aeruginosa [Enterococcus sp., Bacillus pseudomycoides, Staphylococcus sp. (except some S. aureus strains), or P. vulgaris. Weak or no activity against L. monocytogenes, S. enteritidis, Salmonella sp., Shigella flexneri, or Serratia sp. was detected. Alcoholic (methanolic and ethanolic) and water extracts were the most active. Less effective were hexanoic [Screening of the activity of fireweed extracts revealed strong variation in the antimicrobial properties depending on the microbial species and strains. The MIC values ranged from 0.625 \u00b5g/mL to 16.2 mg/mL . The lowtifolium . Very lo. cereus , E. coli[E. coli ,74,75, Pruginosa , and K. eumoniae . Signifi. cereus , S. aure. aureus ,72, E. cruginosa . Moderathexanoic and dichhexanoic . Seed exhexanoic .C. glabrata, C. lusitaniae [M. gypseum [M. gypseum and comparable to berberine (positive control) [M. canis [T. tonsurans [Arthroderma genus, and the most sensitive species was Arthrodermacrocatum (MIC = 19.68 \u00b5g/mL) [T. rubrum (MIC = 16\u2013125 \u00b5g/mL), though the effect was strain-dependent [Candida sp., but the effect was strongly dependent on species and strain. C. tropicalis, C. maltosa, and C. glabrata were more sensitive [Aspergillus niger, A. flavum, A. fumigatus, and Fusarium sp. [Root extracts demonstrated significant antifungal activity against sitaniae , and M. gypseum . The effcontrol) . Strong M. canis and T. tonsurans . The rec8 \u00b5g/mL) . Signifiependent . The extensitive ,67,75. Nrium sp. ,58,62.E. angustifolium extracts have shown strong variation in the biological activity depending on the bacterial species and strain. A strain-dependent antimicrobial effect is well documented, e.g., laurel activity against three Salmonella Typhimurium strains [Listeria monocytogenes [B. subtilis ATCC 6633 [E. faecalis ATCC 29212 [S. aureus ATCC 25923 [50 methods [, FS115) or the aytogenes . Varied TCC 6633 ,64,75, ECC 29212 ,73,76, oCC 25923 ,66,69,71CC 25923 . For the methods ,37,38,80 methods ,63,67,74 methods ,71,73. I methods ,72,75, T methods ,66,69,70 methods , Finland methods , USA [61E. coli and P. aeruginosa, but a flower extract showed a stronger inhibitory effect against S. aureus (11 mm vs. 17 mm) and C. albicans (15 mm vs. 20 mm) [C. albicans strain. The differences in the extracts\u2019 activity might have resulted from their different chemical compositions. Diversity in the organ distribution of the main phenolic compounds in flowers and leaves of E. angustifolium was found by Baert et al. 2017 [O-rhamnoside, myricetin-3-O-rhamnoside, and kaempferol-3-O-rhamnoside were specific to flower tissue and were absent from leaves. Therefore, the different compositions of ellagitannins and flavonoids in flowers and leaves might be responsible for the varied antimicrobial effect. Generally, a weak or moderate effect of seed extract was found . Compara. 20 mm) . Kosalec. 20 mm) . Both exal. 2017 . HexamerE. coli, S. aureus, K. pneumoniae, P. aeruginosa was reported by G\u00fcven at al. 2020 [The other crucial factor is the solvent used for extraction ,82,83. Pal. 2020 . In anotal. 2020 . Alcoholal. 2020 ,86 and sal. 2020 . E. angustifolium extracts were active against both Gram-positive and Gram-negative bacteria. Lower activity against Gram-negative than Gram-positive bacteria was found [Artemisia vulgaris [Eucalyptus grandis [as found ,70,71,73as found , Artemisvulgaris , Eucalyp grandis , etc., a grandis ,91.S. aureus [B. cereus [S. aureus [M. luteus [Staphylococcus aureus (MRSA) strains cause serious and mortal infections in the elderly and in immunocompromised patients [Polyalthia longifolia [Xylopia pancheri [Cistus salviifolius, and Punica granatum [S. aureus including MRSA. Interestingly, punicalagin (ellagitannin) and ellagitannin-rich extracts from C. salviifolius and P. granatum were the most active against 100 S. aureus (50 MRSA) clinical isolates [S. aureus [E. angustifolium ethanolic and aqueous extracts, this group of secondary metabolites might be responsible for the anti-staphylococci effect. However, detailed phytochemical studies are needed to make definitive conclusions.Among Gram-positive bacteria, a high antibacterial effect expressed as a low MIC value (<300 \u00b5g/mL) or as the inhibition zone (>20 mm) was recorded for . aureus ,67,69,72. cereus . It is w. aureus includin. aureus and M. l. luteus . Methicipatients ,93. Therpatients . Accordingifolia , Xylopiapancheri , Cistus granatum , and othisolates . In anot. aureus . RegardiMicrococcus luteus, was sensitive to fireweed extracts [E. angustifolium extract inhibited the growth of M. luteus more effectively than vancomycin or tetracycline (250 \u00b5g/mL). Unfortunately, the extract was not chemically studied, and no pure compounds were comparatively evaluated. Therefore, it is difficult to claim what active compound or class of secondary metabolite was responsible for this antibacterial effect in this case. It is worth noting that the digested extracts tested on probiotic bacteria (Lactobacillus and Bifidobacterium strains) did not inhibit the growth of these beneficial intestinal bacteria [Another Gram-positive bacterial species, extracts . E. angubacteria . This isE. coli [K. pneumoniae [P. aeruginosa [A. baumannii [S. Typhi [E. coli strains showed varying sensitivity to E. angustifolium extracts. Generally, the fireweed extracts showed moderate activity against E. coli. The best effect was observed for the crude whole plant extract [Among Gram-negative bacteria, the best results were recorded for E. coli ,72,74,75eumoniae ,59,66, Pruginosa ,59,66,67aumannii , and S. extract , which iE. angustifolium also showed significant activity against P. aeruginosa and K. pneumoniae with a 23\u201325 mm inhibition zone mainly due to the properties of the solvent [A methanolic extract of solvent . AqueousA. baumannii and P. aeruginosa are pathogens with an urgent need for new antimicrobials, and their carbapenem-resistant strains are included in the WHO list of global priority pathogens classified as critical priority [E. angustifolium [S. aureus, K. pneumoniae, and E. coli strains were most sensitive (MIC = 0.625 \u00b5g/mL). The lowest activity was observed against A. baumannii strains (MIC = 1.25 \u00b5g/mL). The literature provides evidence of the effectiveness of biocidal nanomaterials against resistant bacteria [E. coli and S. aureus [S. aureus and P. aeruginosa [Plantago major [Prunus africana, Camelia sinensis [Tradescantia pallida extracts showed significant antimicrobial effects against S. aureus, E. coli, and P. aeruginosa [S. typhimurium and Y. enterocolitica were 6.2 \u03bcg/mL and 3.1 \u03bcg/mL, respectively [priority . High actifolium . Among tbacteria ,100. Nan. aureus , or S. aruginosa . Green sgo major , Prunus sinensis , and Traruginosa . In anotectively . It is wectively seemed tectively . E. angustifolium extracts showed strong antifungal properties against the dermatophytes M. canis [T. tonsurans [M. canis or T. rubrum in humans [T. rubrum, T. mentagrophytes, and Arthroderma spp., with A. crocatum being the most sensitive species [E. angustifolium extracts were inactive or moderately active against Candida spp. with the exception of C. tropicalis [C. maltose [M. canis and T. tonsurans with then humans . Signifi species . In contopicalis and C. m maltose . Aspergillus and Candida spp., is well documented [T. rubrum, T. mentagrophytes [M. canis [Epilobium parviflorum, the average MIC values against the eight tested strains of T. mentagrophytes isolated from patients was 9.25 mg/mL [E. angustifolium extracts demonstrated much stronger activity, expressed in the MIC value range of 62.3\u2013125 \u00b5g/mL [The resistance of fungal species, i.e., cumented , whereasrophytes ,111, andM. canis ,113,114.25 mg/mL . In this25 \u00b5g/mL . Cymbopogon spp., Eucalyptus robusta, Punica granatum, and S. baicalensis are plant species with strong antifungal properties with an MIC value range of 12.5\u2013100 \u03bcg/mL [E. angustifolium extracts and contribute to the antifungal and antibacterial activities. However, the exact antifungal components of E. angustifolium extracts and their mechanism of action are still unknown. 00 \u03bcg/mL . The mai00 \u03bcg/mL ,117,118.E. angustifolium extracts [E. angustifolium on different lines of cancer cells using bacterial cellulose membranes as the matrix for the controlled delivery of the plant extract. The SEM analysis confirmed the deposition of active compounds inside the membranes and the cytotoxicity effect of the extract was dose and time-dependent. In other words, they confirmed that E. angustifolium extract was able to efficiently penetrate the bacterial membranes and induce apoptosis in the cancer cells.Most authors have attributed the antimicrobial activity of fireweed extracts to their rich polyphenol composition ,69,71,76extracts ,14,119 aextracts . RecentlE. angustifolium leaf extract, rich in tannins (10.41%) and flavonoids (1.9%), was the most active against yeast and S. aureus. In this study, the anti-biofilm effect of plant extracts against MDR E. coli strains was also investigated. Polygonum bistorta extract was most active (MIC 10 \u00b5g/mL), whereas E. angustifolium extract showed moderate activity (50\u2013100 \u00b5g/mL). The result of correlation analysis of anti-biofilm activity and tannin content was moderate but statistically significant, but no correlation between flavonoids and anti-biofilm activity was found. This was surprising, because flavonoids are biofilm-inhibiting compounds. The authors explained that the assay used to evaluate biofilm inhibition did not reflect the full potential of the flavonoids and in the applied method, flavonoid content was calculated as hyperoside, which has comparatively low anti-biofilm activity. Regardless of this study, tannins and flavonoids are considered as the main contributors of antimicrobial activity [Neumann et al. 2022 tested 1activity ,121,122.Tannins might inhibit bacterial growth using different mechanisms such as inhibition of cell wall synthesis, iron chelation, disruption of the cell membrane, or inhibition of the fatty acid biosynthetic pathway . The bioStaphylococcus aureus, Escherichia coli, and Clostridium perfringens was documented [S. aureus and the weakest for C. perfringens. Salicarinin A and rugosin D inhibited the growth of S. aureus completely at a 0.5 mM concentration. Tellimagrandin II, rugosin D, agrimoniin, sanguiin H-6, and lambertianin C were the most efficient compounds against E. coli. The antibacterial effect against S. aureus was not clearly related to the molecular size or flexibility of ellagitannins; however, rugosins E and D and pentagalloylglucose with four or five free galloyl groups demonstrated stronger activity than the other ellagitannins with glucopyranose cores. The oligomeric linkage of ellagitannin and the number of free galloyl groups in pentagalloylglucoses were suggested as crucial factors in activity against E. coli. In turn, the antimicrobial effect against C. perfringens was attributed to the molecular size of ellagitannins. It should be added that macrocyclic ellagitannins such as oenothein B or A were not tested in this study. Oenothein B demonstrated antimicrobial properties against Helicobacter pylori, Staphylococcus aureus as well as fluconazole-sensitive and -resistant Candida albicans, C. tropicalis, and C. glabrata strains [S. aureus lactoferrin, whereas the phenolic hydroxyl groups were not associated with lactoferrin [The antibacterial effect of ellagitannins against cumented . The eff strains ,127,128.The antimicrobial activity of fireweed extracts was also related to the presence of flavonoids, particularly to quercetin and kaempferol ,71,74. SE. angustifolium flavonoids, are known to have antibacterial and antiviral properties [O-rhamnoside (myricitrin) was effective against B. cereus, E. coli, S. aureus, and K. pneumoniae [Quercetin and its derivatives, which are the predominant compounds among operties ,130. In eumoniae ,132. Flaeumoniae ,133,134.S. aureus [E. coli strains [H. pylori [O-caffeolyqunic, neochlorogenic, and chlorogenic acids were identified as the most potent anti-inflammatory constituents of E. angustifolium extract [Significant antimycotic properties of gallic, ellagic, and chlorogenic acids have been mentioned above. However, antibacterial activity against methicillin-resistant . aureus , MDR E. strains , and H. . pylori has also. pylori . 4-O-caf extract . Chlorog extract ,139,140. extract ,142. A mC. salviifolius extract was more effective against MRSA isolates, whereas P. granatum extract was more active against methicillin-sensitive S. aureus (MSSA) isolates [C. salviifolius extract contained more flavonoids (myricetin and quercetin derivates), phenolic acids and coumarins. E. angustifolium plants are a rich source of hydrolysable tannins and flavonoids. Considering the chemical composition of E. angustifolium extracts and the antimicrobial potential of their constituents, the synergistic mechanism of action should be suggested rather than the activity of a certain compound at high concentration.The antibacterial activity of extracts might also be modulated and affected by the presence of other compounds. Notably, isolates . Both exEpilobium angustifolium L. extracts. The time range was set between January 2000 and June 2023. In all searches, the following terms were used: \u201cEpilobium angustifolium\u201d/\u201cChamerion angustifolium\u201d/\u201cChamaenerion angustifolium\u201d and \u201cantibacterial\u201d/\u201cantifungal\u201d/\u201cmedicinal plants with antibacterial properties\u201d. The search was not limited to title, keywords, and abstract, but the text of the articles was also explored. The obtained records of databases were further explored for articles that may match the search criteria. Studies were considered if they met the following criteria: (1) plant species\u2014Epilobium angustifolium, (2) extracts prepared from plant material , (3) antibacterial or antifungal studies, (4) article written in English. Essential oils, honey, food supplements, and cosmetic products were excluded. The literature search yielded the following number of records: Scopus (29), PubMed/Medline (79), and Google Scholar (123). Reviews, conference proceedings, and articles concerning biological activities of E. angustifolium extracts without antimicrobial activities were not included. After rigorous selection, removing duplicates and irrelevant articles, only 23 articles were considered for this review or as in inhibition zones (>20 mm) was recorded for S. aureus, B. cereus, E. coli, K. pneumoniae, P. aeruginosa, E. coli, S. Typhi, and A. baumannii including methicillin-resistant strains. The antimicrobial activity of fireweed is attributed more to the rich polyphenol composition of extracts and their synergic interactions than the activity of a certain compound at a high concentration. Although the standardization of antimicrobial studies and the methods of chemical analysis of extracts have improved over the last decade, there is still a need for further improvement of methodological quality and comparative studies including isolated substances. Another challenge is the lack of adequate knowledge on the compositions and mechanisms of action of extracts. Nevertheless, the interesting results of the cited studies suggest potential utilization of fireweed extracts as antimicrobials in wound healing, components of cosmetic products for humans and animals, or a food preservative.The reviewed literature showed a broad spectrum of antimicrobial activity of"} +{"text": "Corentin Warnier, Thibault Gendron, Muhammad Otabashi, Charles Vriamont and Alex Jackson were not included as authors in the original publication . The corAuthor Contributions: A.P.: conceptualisation, investigation, original draft; F.Z.: review, conceptualization; C.W.: methodology, conceptualization; T.G.: methodology, conceptualization; M.O.: methodology, conceptualization, validation; C.V.: methodology, conceptualization; A.J.: funding acquisition, resources, conceptualisation; W.P.F.: funding acquisition, review; K.H.: funding acquisition, review; M.N.: review. All authors have read and agreed to the published version of the manuscript.In the published publication, the following two affiliations are missing:2 Trasis, Rue Gilles Magnee 90, 4430 Ans, Belgium3 Theragnostics Ltd., 1 Sans Walk, London EC1R 0LT, UKIn the original publication, there was a mistake in Funding. The correct version should be:Funding: This research was funded by Theragnostics Ltd.A correction has been made to Conflicts of Interest. The updated text appears below.Conflicts of Interest: Alex Jackson is an employee of Theragnostics Ltd. Charles Vriamont, Corentin Warnier, Thibault Gendron and Muhammad Otabashi are employees of Trasis.The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models \u2013 inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds \u2013 amino acids, lipids, carbohydrates, nucleic acids fragments \u2013 in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism , of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes , all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease. Hypertension is a complex multifactorial disease determinedby both genetic and environmental factors, as well as the effectsof genotype-environment interactions. Currently, a wideselection of antihypertensive drugs and their combinationsis available for clinical medicine . However,only a few of them are actually used : they affectthe final links in the pathogenesis of arterial hypertension andusually do not address the initial etiological mechanisms ofthe disease. This can partly explain the fact that only 30 % ofhypertensive patients successfully achieve and control bloodpressure (BP) targets .To improve the effectiveness of assigned therapy, objectivecriteria that enable positive identification of the individualetiological and pathogenetic characteristics of the diseaseare needed. First of all, of interest are genetic markers. Genesassociated with arterial hypertension have been identified innumerous studies, including genome-wide analysis of a hugenumber of polymorphisms. However, these polymorphic lociaccount for only a small percentage (2\u20133 %) of BP variabilityin the tested populations . Obviously,the contribution of environmental factors, as well as the effectsof genotype-environment interaction, dominates. Non-additiveintergenic interactions and epigenetic influences may alsobe of great importance .In recent decades, along with the analysis of the genomeand transcriptome, metabolomic and proteomic studies havebeen developed. Metabolic profiles of biological tissues representthe influence on the metabolism of both genes and theenvironment, which makes it possible to obtain an integralassessment of multifactorial influences. Therefore, the searchfor metabolic markers, along with genetic ones, provides amore comprehensive picture of pathogenetic processes occurringin a particular person, and also allows clustering patientsaccording to various forms of hypertensive conditions. Awarenessof the metabolic pathways underlying a particular typeof arterial hypertension would make the treatment protocolsmore efficient .Comprehensive metabolomic studies of arterial hypertensionpathogenesis are still few in number. However, hypertensivepatients were found to have specific changes in thelipid profile of blood serum , changesin carbohydrate metabolism \u2013 an increase in glucose andgalactose levels and a decrease in fructose concentration , an increase in the concentration of alpha-1-acidglycoprotein, a marker of inflammatory processes . Some data were also obtained on the metabolicprofile in the strain of rats with spontaneous hypertension \u2013SHR: an age-related decrease in the concentrations of certainamino acids and an increase in the content of free fatty acids in bloodplasma , reduced in comparison with normotensivecontrol rats urinary citrate and alpha-ketoglutaratelevels at 8 weeks of age , increased urinarytaurine and creatine at 12 and 26 weeks of age .In the present study, for the first time, we analyzed themetabolic profile of blood serum in experimental animals withhereditary stress-sensitive arterial hypertension \u2013 ISIAH rats.Experimental animals. Male ISIAH rats with inheritedstress-induced arterial hypertension (n = 10), control normotensivemale WAG rats (Wistar Albino Glaxo) (n = 10),all aged 3\u20134 months. The experimental animals were keptunder standard conditions in the conventional vivarium ofthe Institute of Cytology and Genetics (Siberian Branch ofthe Russian Academy of Sciences \u2013 SB RAS), receivingstandard chow and drinking water ad libitum.All procedures involving animals complied with the ethicalstandards approved by the legal acts of the Russian Federation,the principles of the Basel Declaration and the recommendationsof the Inter-Institute Committee on Biological Ethics atthe Institute of Cytology and Genetics (SB RAS) .Blood pressure monitoring. Performed on a device fornon-invasive blood pressure measurement using the tail-cuff method, after preliminary adaptation ofanimals to this procedure for 3\u20134 days.Blood serum sampling. Carried out during the euthanasiaof experimental animals by decapitation. Collected peripheralblood was kept for an hour to form a primary clot, then centrifuged , the obtained blood serumwas stored at \u201370 \u00b0C.Extraction of metabolites from blood serum samples.Performed at the Research Equipment Sharing Center\u201cMass-spectrometric Studies\u201d of the International TomographyCenter (SB RAS), at the Laboratory of Proteomics andMetabolomics. Metabolites were extracted using a mixtureof methanol-chloroform-water in the ratio of 1:1:1, accordingto a previously developed protocol . The volume of serum for the studywas 300 \u03bcl. The lyophilized extracts were diluted in 600 \u03bclof deuterated phosphate buffer with the additionof internal standard DSS (2 \u00d7 10\u20135 M 3-(trimethylsilyl)propane-1-sulfonate sodium).NMR spectra. Obtained on the AVANCE III HD 700 MHzNMR spectrometer equippedwith an Ascend cryomagnet with a field strength of 16.44Tesla. The survey parameters are described in earlier articles. MestReNovav12.0 software was used to process the spectra and integratethe signals.Identification of metabolites in the studied samples.Carried out using the Human Metabolome Database (https://hmdb.ca/) and our own data on the metabolic profiles of humanand animal biological fluids .Statistical processing of metabolomic data. Performedusing the Statistica 8 software package (http://statsoft.ru/) andthe MetaboAnalyst 5.0 web platform , applying multivariate statistics and non-parametric methodfor assessing intergroup differences (Mann\u2013Whitney U-test).Values at p < 0.05 were considered statistically significant.As a result of the NMR spectra analysis, the concentrations of56 metabolites were determined in the blood serum of ISIAH(BP = 205.6 \u00b1 7.3 mm Hg) and WAG (BP = 136.6 \u00b1 3.1 mm Hg)rats. Significant interstrain differences in serum concentrationsof 18 metabolites were observed (see theTable).In ISIAH rats, the concentrations of leucine, isoleucine,valine, isobutyrate, glutamate, glutamine, asparagine, creatinephosphate, ornithine, myo-inositol, histidine, 1-methylhistidine,methionine sulfoxide in blood serum were significantlyhigher than in WAG rats, whereas the concentrations of 2-hydroxyisobutyrate,2\u2032-deoxyuridine, betaine, tryptophan, andtyrosine in ISIAH rats were decreased compared to normotensivecontrols.In order to isolate metabolites that are associated with elevatedblood pressure in ISIAH rats, a multivariate analysiswas performed. Principal component analysis revealed twomain factors (two axes) that together account for 47.2 % ofthe total variation in serum concentrations of the studiedmetabolitesAs can be seen from Fig. 1, the experimental animals wereclustered in the space of two principal components on thebasis of belonging to a hyper- or normotensive strain. Theprojections of these clusters on the axis of the first component practically do not overlap, while their projections onthe axis of the second component coincide. Thus, the firstprincipal component can be defined as the axis of presence/absence of hypertensive status. In order to establish a relationshipbetween the concentrations of the detected metabolitesand the hypertensive status, it is necessary to consider theirdistribution against the first principal component. This isdetermined by the \u201cloadings\u201d that metabolites make on thefirst component.Positive loadings on the axis of the first component weremade by 2-hydroxyisobutyrate, tryptophan, tyrosine, betaine,2\u2032-deoxyuridine; ornithine, valine, isoleucine, leucine, isobutyrate,glutamate, glutamine, asparagine, creatine phosphate,myo-inositol, histidine, 1-methylhistidine, methionine sulfoxidemade negative loadings . Thus, the listed metabolitesare largely responsible for the clustering of groupsof experimental animals according to the level of their bloodpressure.\u0412\u0421\u0410\u0410, branched-chain amino acidsAmino acids of the BCAA group \u2013 leucine, isoleucine andvaline \u2013 are essential, and participate in the protein synthesisand degradation. They are also signal molecules in glucosemetabolism, activating the mTORC1 complex, which phosphorylatesthe insulin receptor substrate IRS-1 . Elevated plasma concentrations of BCAAamino acids have been associated with obesity, insulin resistance,decreased glucose tolerance, and type 2 diabetes,according to a number of studies . It has also beenfound that leucine, isoleucine, and valine are involved in thehypothalamic regulation of glucose metabolism in the liver.Prospective cohort studies involving a large number ofpatients and 27,041 ) show that elevated plasma concentrations of BCAAamino acids positively correlate with the risk of developingcardiovascular diseases . In ISIAH rats, a decrease in the level ofimmunoreactive insulin in the blood and glucose tolerancehas been previously found, probably due to a geneticallydetermined increased activity of the sympathoadrenal andthyroid systems .Activation of the pancreas sympathetic innervation reducesinsulin production by \u03b2-cells, acting through \u03b12-adrenergicreceptors , and thyroid hormones affect insulin production through the regulation of insulin-likegrowth factor 1 secretion . These dataare consistent with the results of the present study: the concentrationsof leucine, isoleucine, and valine in blood serumare significantly increased in ISIAH rats compared to controls(see the Table), which suggests that amino acids of the BCAAgroup can be considered as metabolic markers of hereditarystress-induced arterial hypertensionMyo-inositolSome inositol isomers (particularly myo-inositol) have insulinlikeproperties and may reduce insulin resistance in patientswith metabolic syndrome . It has been shown that myo-inositol plasmalevel is associated with BP level in patients with hypertension, and the use of myo-inositol as part ofa dietary supplement for six months reduced the concentrationof cardiovascular diseases biomarkers in menopausalwomen and in women with a history of metabolic syndrome. It is assumed that inositol derivativesaffect the IP3 receptor, which regulates the contractility of thesmooth muscle walls of blood vessels through L-type calciumchannels . An increased level ofmyo-inositol in the blood serum of ISIAH rats with hereditarystress-induced hypertension may indicate its involvement inthe pathogenesis of the hypertensive status of rats of this strain.SCFA, short-chain fatty acidsShort-chain fatty acids \u2013 formic, acetic, propionic, butyric,isobutyric, valeric, isovaleric and others \u2013 are produced in thelarge intestine during fiber fermentation, being an importantsource of energy for colonocytes, and having anti-inflammatoryand antitumor properties . Short-chain fatty acids entering into acylationreactions can modify histones, thus regulating the expressionof genes involved in the mechanisms of development of themetabolic syndrome, type 2 diabetes, and ischemic tissuedamage . Decreasedproduction of short-chain fatty acids produced by gut bacterialeads to intestinal dysfunction, inflammation, kidney failure,and, as a result, to increased blood pressure . In SHR rats with spontaneous hypertension,elevated BP has been associated with a reduced contentof acetate and butyrate-producing bacteria in the intestinalmicrobiota .The relationship between BP levels and various acids of theSCFA group in salt-sensitive Dahl rats has also been studied:a high salt load resulted in an increase in the concentrationof acetate, propionate and isobutyrate in fecal samples . Mechanisms of this relationship have not yetbeen studied in detail, but there is evidence that short-chainfatty acids can affect vessels and kidneys through endothelialreceptors associated with G-proteins, which leads to a changein BP levels . In hypertensive ISIAHrats, a change in the ratio of SCFAs and their derivativeswas also observed when compared with the normotensivecontrol: isobutyrate blood concentration was significantlyincreased, while 2-hydroxyisobutyrate levels were decreased(see the Table).Glutamate, glutamineAssociations of glutamate and glutamine concentrations, aswell as hepatic aspartate aminotransferase activity, with insulinresistance and the development of the metabolic syndromehave been shown . There is also evidencethat plasma glutamate is positively correlated with bloodpressure, body mass index, insulin and triglyceride levels.The glutamine/glutamate ratio is inversely related to theseparameters . Considering that ISIAH ratsin this study have increased serum levels of both glutamateand glutamine when compared to control WAG rats, but theglutamine concentration (894.53 nmol/ml) is several timeshigher than the glutamate content (208.58 nmol/ml), interpretationof observed interstrain differences in glutamate andglutamine concentrations requires more research.Glutamate and glutamine also contribute to the metabolismof arginine and ornithine, which are involved in the urea andnitric oxide cycle . Ornithine concentrationin the serum of ISIAH rats is also increased comparedto the control. It is established that \u03b1-difluoromethylornithineadministration resulted in the restoration of endothelial functionand prevented an increase in blood pressure in spontaneouslyhypertensive SHR rats . In anearlier SHR study, \u03b1-difluoromethylornithine reduced the rateof aortic and caudal artery contraction in response to electricalstimulation and norepinephrine administration, while adecrease in arterial wall thickness and a decrease in the contentof polyamines in vessels was also observed .Metabolites associated with inflammationIn a study involving healthy volunteers (323 people) andischemic stroke patients (323 people), choline, like its metabolitebetaine, was found to reduce the risk of cardiovascularcomplications . Long-term use of cholineand betaine as a dietary supplement was also shown to lowerblood pressure in hypertensive patients . Intragastric administration of betaine to rats modelingpulmonary hypertension resulted in a decrease in rightventricular and pulmonary artery blood pressure, in a decreasein the degree of ventricular hypertrophy and in remodeling ofthe arterial wall, presumably due to anti-inflammatory action \u2013betaine also reduced the levels of MCP-1, ET-1, NF-\u03baB,TNF-\u03b1, IL-1\u03b2 .Tryptophan is an essential aromatic amino acid. In mammals,tryptophan is metabolized in three partially overlappingpathways. The main pathway \u2013 kynurenine pathway \u2013 includesoxidation and destruction of the indole ring, producing derivatives:kynurenic and anthranilic acids. One of the 60 tryptophanmolecules is converted into nicotinic acid . The second pathway is the serotonin pathway, wheretryptophan is converted to serotonin and melatonin. Thethird pathway is the indole pathway, the formation of indolederivatives, which are then excreted in the urine . It has been shown that disorders in the links of thekynurenine pathway facilitate development of cardiovasculardiseases, including an increase in blood pressure . It is possible that tryptophanand kynurenine promote vasodilation through participationin the adenylate cyclase and guanylate cyclase systems ofsecondary intracellular messengers, triggering a cascade of reactions leading to the activation of nitric oxide receptors andto a decrease in the concentration of Ca2+ ions in the smoothmuscle walls of blood vessels .Betaine and tryptophan concentrations were significantlyreduced in the blood serum of hypertensive ISIAH rats compa-red with normotensive control, which may indicate that inflammatoryprocesses play a role in establishing and maintainingthe hypertensive status of ISIAH rats. Recently, there hasbeen even more evidence of the important role of vascularwall inflammation in the pathogenesis of hypertensive conditions,including those involving interleukins IL-1\u03b2 and IL-18.Metabolites associated with energy processesCreatine phosphate is a source of rapidly mobilized energyin tissues where energy metabolism is most intense \u2013 skeletalmuscles, myocardium, brain. Due to the fact that direct transportof ATP across the mitochondrial membrane is difficult, creatinephosphate serves as a \u201cshuttle\u201d, participating in the transport ofchemical energy between mitochondria and energy-consumingareas. ATP with mitochondrial creatine kinase phosphorylatescreatine to creatine phosphate, which goes, for example, to myofibrils.Myofibrillic creatine kinase forces creatine phosphateto phosphorylate ADP to ATP, producing creatine, which againreturns to the mitochondria, and the cycle repeats .Changes in the content and ratio of creatine and phosphocreatinein tissues can be a signal of various pathologies. It has been shown that a decrease in theratio of creatine phosphate/ATP correlates with the severityof heart failure and with the severityof myocardial hypertrophy . It is also knownthat exogenous creatine phosphate administration has a cardioprotectiveeffect on the ischemic myocardium . In our study,in ISIAH rats, serum creatine phosphate concentration wasincreased nearly three-fold compared with the normotensivecontrol. To explain this difference in peripheral concentrationsof creatine phosphate, additional studies are required,including an assessment of creatine phosphate concentrationand the ratio of creatine phosphate/ATP in the myocardiumof hypertensive ISIAH rats.Metabolites associated with the synthesis of catecholaminesTyrosine is an aromatic amino acid from which, via enzymetyrosine hydroxylase, catecholamines are synthesized: dopamine,adrenaline, norepinephrine. Catecholamines arethe main effectors of the sympathoadrenal system, affectingcardiac output and vascular resistance . Themain indicators of the sympathoadrenal system functionsare catecholamine concentrations and tyrosine hydroxylaseactivity , but tyrosineconcentration may also be considered as a marker ofcatecholamine synthesis disorders: for example, in a metabolomicstudy of urine samples from patients with hypertensivenephrosclerosis, a decrease in tyrosine and dopamine levelshas been found .It has previously been shown that the production of epinephrineby the adrenal glands and norepinephrine in the brainis increased in ISIAH rats compared with WAG , which allows to suggest thatthe reduced serum tyrosine level in ISIAH rats is a marker ofchanges in catecholamine synthesis.Thus, we conclude that the metabolic profile of blood serum,which indicates the presence of a stress-dependent formof arterial hypertension, can be described as follows: anincrease in the concentrations of leucine, isoleucine, valine,myo-inositol, isobutyrate, glutamate, glutamine, ornithine,creatine phosphate, and a decrease in the concentrations of2-hydroxyisobutyrate, betaine, tryptophan, tyrosine. Elevatedconcentrations of leucine, isoleucine, valine, and myo-inositolare associated with glucose metabolism and insulin resistanceobserved in ISIAH rats . Ornithine plays an important role in the urea synthesis,and is also associated with the metabolism of arginine and theproduction of vasoactive factor \u2013 nitric oxide; therefore, itsconsideration as a metabolic marker of hypertension pathogenesisseems to be quite reasonable. 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DOI 10.1093/ajcn/nqab199."} +{"text": "Communications Biology 10.1038/s42003-023-05210-5, published online 23 August 2023.Correction to: In the original version of the Article, two authors and their affiliations were omitted.In the original version of the Article, author first names were not provided for all authors.The corrected author list and affiliations are provided below. This has now been corrected in the HTML and PDF versions of the article.1, David R. Begun2, Alper Yavuz3, Erhan Tarhan4, \u00c7ilem S\u00f6nmez S\u00f6zer1, Serdar Mayda5, Lars W. van den Hoek Ostende6, Robert M. G. Martin2 & M. Cihat Al\u00e7i\u00e7ek7Ayla Sevim-Erol1 Ankara University, Faculty of Languages History and Geography, Department of Anthropology, Ankara, T\u00fcrkiye2 Department of Anthropology, University of Toronto, Toronto, ON, Canada3 Mehmet Akif Ersoy University of Science and Letters, Department of Anthropology, Burdur, T\u00fcrkiye4 Hitit University Faculty of Science and Letters, Department of Anthropology, \u00c7orum, T\u00fcrkiye5 Ege University Fakulty of Science, Department of Biology, \u0130zmir, T\u00fcrkiye6 Naturalis Biodiversity Center, Leiden, The Netherlands7 Pamukkale University, Department of Geology, 20070 Denizli, T\u00fcrkiyeThe Author Contributions section should read \u201cA.S.E. is the PR of the project, secured funding for excavations and lab analysis and directed excavations. A.S.E. and D.R.B. are responsible for data curation, acquired funding and supervised research. D.R.B. conceptualized the analysis, conducted the investigation, developed the methodology, prepared the original draft and all subsequent versions. C.S.S., S.M., L.W.vdH. and C.A. contributed their analysis of geological and paleontological results. R.M.G.M. was responsible for the segmentation and analysis of the scans of the mandible. A.Y and E.T. participated in the excavations.\u201d This has now been corrected in the HTML and PDF versions of the article."} +{"text": "Neottialihengiae, Neottiachawalongensis, Papilionanthemotuoensis, Gastrochiluslihengiae, and Gastrochilusbernhardtianus, are described and illustrated. To confirm their identities, and to resolve phylogenetic relationships, we sequenced the complete plastomes of these taxa with their congeneric species, adding new plastomes of three Neottia species, two Papilionanthe species and nine Gastrochilus species. Combined with published plastid sequences, our well-resolved phylogeny supported the alliance of N.lihengiae with the the N.grandiflora + N.pinetorum clade. Neottiachawalongensis is now sister to N.alternifolia, while P.motuoensis is closely related to P.subulata + P.teres. Conversely, phylogenetic analyses based on complete plastomes and plastid sequences showed inconsistent relationships among taxa in the genus Gastrochilus, but the two new species, G.lihengiae and G.bernhardtianus were supported by all datasets.Five new orchid species from southwestern China\u2019s Yunnan Province and the Tibetan Autonomous Region, Orchidaceae as an example, early floristic accounts of Tibet (Xizang) in the \u201cFlora Xizangica\u201d included only 64 genera totaling 191 species or it is leafless. Each resupinate flower contains a curved column containing two sectile but naked pollinia .The genus orchids . Recent hidaceae . There aern Asia . MorpholPapilionanthe Schltr., a member of Vandeae (subtribe Aeridinae), was first described by Schlechter in 1915 based on Vandateres (Roxb.) Lindl. published previously in genus Vanda R.Br. The genus Papilionanthes.s. is distinguished from other genera in subtribe Aeridinae by multiple characters. It has fleshy and terete leaves, and a short inflorescence arising from a node opposite the leaf. The trilobate labellum is spurred. Its mid-lobe is often dilated and 2- or 3-lobed at its apex. The subterete and short column has a short foot. Pollinia are attached to a broadly triangular or subquadrate stipe which, in turn, is attached to a large and cellular viscidium , Papilionanthe and Gastrochilus respectively. These species are analyzed and described below.We collected specimens of five previously unidentified species during our field surveys in Yunnan and Tibet from 2016\u20132023. Following a review of the literature see , morpholHerbarium of the Kunming Institute of Botany, Chinese Academy of Sciences (KUN) and the Herbarium of the Yunnan Academy of Forestry and Grassland (YAF).Living plants and herbarium specimens were collected in the field in the Hengduan Mountains of northwestern Yunnan and the Himalaya of southeastern Tibet. Morphological characters and measurements of the specimens described here were based on at least 5 living specimens first observed in the field then cultivated plants in the greenhouse. Voucher specimens are deposited in the Neottia species, two Papilionanthe species and nine Gastrochilus species. Including those retrieved from the National Centre for Biotechnology Information (NCBI) database, our dataset comprises 412 plastid genes of a total of 83 accessions.To clarify the phylogenetic relationships of five potentially new species with closely related species, we sampled and sequenced plastomes of 17 accessions representing three Neottiaovata (L.) Hartm. (NC_030712) and Gastrochilusformosanus (Hayata) Hayata (MN124435) were used as references for the assembling of the clean reads (ITS) assembly were conducted using the Getorganelle toolkit Christenson (NC_041511.1) and Gastrochilusformosanus . Libraries for pair-end 150 bp sequencing with 200\u2013400 bp insert size were conducted on a BGISEQ-T7 platform at BGI Shenzhen (China) for genome skimming, producing approximately 2Gbp high-quality reads per sample. The plastomes of an reads . Complet toolkit . The parrmosanus .Neottia, a total of 22 taxa were included in the analysis of the data set comprising two plastid DNA and nuclear ribosomal (nr) ITS sequences, Cephalantheralongifolia (L.) Fritsch was used as the outgroup based on Papilionanthe, phylogenomic analysis was implemented based on nrITS and six plastid markers from 6 Papilionanthe species, including two newly sequenced species, and a total of 12 accessions representing four genera. They were all analyzed with Ascocentrumampullaceum (Roxb.) Schltr. as the outgroup . Therefore, a total of 17 Gastrochilus plastomes were included in this study with Pomatocalpaspicatum Breda as the outgroup model was selected in JModelTest v2.1.10 (ML) in RaxML v8.2.11 (BI) methods in Mrbayes v3.2.6 (MCMC) chains were run for 200,000 generations with mixed nucleotide substitution models and 25% of the trees were deleted as burn-in, and the results of two independently run computations were merged to produce a Bayesian consistent tree and a posterior probability value (PP) for each branch.For outgroup . For Gasoutgroup . DNA seqocks 0.91. Before v2.1.10 . Phyloge v8.2.11 with 1,0s v3.2.6 . For BayNeottia) and 29\u201330 tRNA genes and 4 rRNA genes. While, all three newly sequenced Neottia plastome sizes ranged from 155,447\u2013156,082 bp, their genomes were composed of an LSC region , SSC region and two IR copies , with 74\u201380 unique genes. Their overall G/C content was almost identical (37.5\u201337.6%). The total plastome lengths of Papilionantheteres (Roxb.) Schltr. and the putative new species, P.motuoensis ranged from 147,829\u2013148,619 bp. Among all Gastrochilus plastomes, plastome sizes ranged from 146,615 to 148,552 bp. The genomes were composed of a large single repeat region (LSC) , a small single repeat region (SSC), region and two inverted repeat (IR) copies . Their overall G/C content was nearly identical (36.6\u201336.8%).All newly sequenced plastomes were assembled completely and can be accessed from GenBank Table . Their gmatK, rbcL) data indicated that Neottia s.l. is monophyletic with moderate support . Within the sampled species, the widespread and temperate N.ovata diverged initially, which is consistent with the previous study by N.cordata (L.) Rich. and N.smallii (Wiegand) Szlach. The newly discovered species N.chawalongensis Szlach. . Together, they constitute the sister clade of N.meifongensis (H.J.Su & C.Y.Hu) T. C. Hsu & S. W. Chung. The second new species, N.lihengiae Szlach. the unidentified Neottia sp. and N.wardii (Rolfe) Szlach. .Phylogenetic relationships based on combined nrITS and plastid DNA , and the combined dataset of 7 markers comprised 8558 aligned nucleotides, 790 bp from nrITS and 7768 bp from plastid regions, respectively.In the overall matrix of Papilionanthe is monophyletic. The main clade of Papilionanthe is divided into two subclades Garay and P.hookeriana (Rchb.f.) Schltr. are sister species. In the second subclade, P.uniflora (Lindl.) Garay diverged first while the newly sequenced P.teres is well supported as sister to P.subulata (Willd.) Garay . Collectively it is sister to the new species P.motuoensis (see below) . The BI and maximum likelihood (ML) trees yield the same topology. The posterior probabilities and bootstrap probabilities values are high, indicating a high degree of confidence for the result. However, this topology is inconsistent with the previous study by P.hookeriana and P.biswasiana, now consisting of a sister group in this study.The concatenated tree of nrITS and its plastid data show that des Fig. . In the Gastrochilus species were included in this study to represent all six sections, 12 accessions representing nine species were newly generated in this study. Their relationships were confirmed using a combined dataset of nrITS and plastid matK, trnL-trnF, psbA-trnH, psbM-trnD sequences analyses of the concatenated sequence supermatrix produced similar topologies for the Gastrochilus species. Gastrochilus s.l. is strongly supported as monophyletic with high posterior probabilities (PP) and bootstrap probabilities (BP) , successively followed by clade B (G.sect.Brachycaules) , clade C (G.sect.Gastrochilus) and clade D (G.sect.Acinacifolii) . Clades E and F are sister to each other and they together comprise a clade sisiter to clade D. Our two new species, G.lihengiae (see below) and G.bernhardtianus (see below) are resolved as distinct species in clade E (G.sect.Microphylli) in all data sets. Gastrochilusdistichus (Lindl.) Kuntze + G.prionophyllus H. Jiang, D. P. Ye & Q. Liu is sister to G.lihengiae while G.heminii M. Liao, B. Xu & Yue.H. Cheng is sister to G.bernhardtianus and they consisting a sister group to G.alatus. Within clade F, two samples of G.gongshanensis Z.H.Tsi and two unidentified species from the Dali, Yunnan form a distinct subclade, which is sister to G.yunlongensis W. H. Rao, L. J. Chen & Z. J. Liu.A total of 41 ces Fig. . The detBP) Fig. . The genGastrochilus specimens provide a wealth of information to determine phylogenetic relationships within this genus, including a fully resolved phylogenetic tree with almost 100% bootstrap values and 1.00 posterior probabilities, and are better supported than in the studies of G.fargesii . In contrast, the remaining four species, are known only from type localities and adjacent areas. For each of these species, only one or two populations with few individuals were detected during our two to three field surveys. More extensive fieldwork is needed to objectively assess their conservation status.. Therefore, the status of all remaining species are temporarily rated as Data Deficient (DD).We preliminarly assesed the conservation status of the five new species using the IUCN Red List Categories and Criteria . NeottiaTaxon classificationPlantaeAsparagalesOrchidaceae\ufeff1.J.D.Ya, H.Jiang & D.Z.Lisp. nov.9E91EFA0-BE0D-5065-8D5D-2192327335FCurn:lsid:ipni.org:names:77331171-1Neottialihengiae is morphologically similar to N.biflora (Schltr.) Szlach., but can be distinguished by its smaller plant size, ca. 5.5\u20139.0 cm tall , its lax rachis of 2\u20135\u2013flowered (vs. 1- or 2-flowered), floral bracts and sepals longer than their pedicel (vs. shorter than pedicel), smaller flowers with sepals and petals connivant and ca. 3.0 mm long (vs. spreading and ca. 6.0\u20137.0 mm long). The outer surfaces of the sepals are not carinate (vs. carinate). The labeullum is ligulate and its midvein is not thickened (vs. cuneate and midvein slightly thickened). The rostellum is almost equal to the anther (vs. distinctly shorter than the anther).KUN! isotype: KUN!)China. Yunnan Province, Diqing Prefecture, Shangri-La County, Tianbao mountain, 3800 m, under shrubs of a scree slope, 4 July 2020, J.-D. Ya et al. 20CS19095 ; Yunnan Province, Diqing Prefecture, Shangri-La County, Tianbao mountain, 3719 m, under the shrub of scree slope, 15 Aug. 2018, C. Liu et al. 18CS17401 (paratypes: KUN!). N.biflora: China. Sichuan, Dongrergo, K. A. H. Smith 3656 . N.tianschanica: China. Xinjiang Uygur Autonomous Region, Tian-Shan, 18 July 1957, K.-Z. Guan 172 ; China. Xinjiang Uygur Autonomous Region, Urumqi, Houxia Zhen, 2161 m, J.D. Ya et al. 17CS16209 (KUN1437961!).China. Yunnan Province, Lijiang City, Gucheng District, Dadong Xiang, 3192 m, in the scree slope area under the forest dominated by Taxon classificationPlantaeAsparagalesOrchidaceae\ufeff2.J.D.Ya & D.Z.Lisp. nov.FECD1EEB-3A25-50F9-8986-C156B026525Durn:lsid:ipni.org:names:77331172-1Neottiachawalongensis is similar to N.pinetorum (Lindl.) Szlach., but differs in having floral bracts longer than its pedicel (vs. shorter or as long as pedicel), a reduced pedicel ca. 1.9 mm (vs. 4\u20136 mm), and a shorter but pubescent ovary, ca. 2.8 mm . The labellum is lanceolate , densely papillate (vs. slightly papillate), with labellum lobes narrowly lanceolate and apices acuminate (oblong-ovate and apices obtuse-rounded) while its sinus usually lacks a short tooth between the lobes.KUN!)China. Tibetan Autonomous Region, Linzhi City, Chayu County, Chawalong Township, 3757 m, under the shrub of scree slope, 21 July 2022, J.-D. Ya et al. 22CS22851 Township.Abies and Picea at an elevation of 3757 m a.s.l. It appears to be locally abundant with other orchid species including Ponerorchischusua (D. Don) So\u00f3, Galearisspathulate (Lindl.) P. F. Hunt, Cypripediumwardii Rolfe, C.bardolphianum W.W.Sm. & Farrer and C.flavum P. F. Hunt & Summerh.At present, this new species is only found in Chawalong, Chayu, Tibet (Xizang), China. It is a predominantly terrestrial species growing on the scree slopes under the forest of N.pinetorum: India. Sikkim, 10\u201311000 feet., J. D. Hooker 355 ; China. Yunnan, upper Kiukiang valley, 2500 m, T.T.Yu 19644 (PE00027188!). N.bambusetorum: China, Yunnan, Prope fines Tibeto-Birmanicas inter fluvios Lu-djiang et Djiou-djiang (Irrawadi or. sup.), in jugi Tschiangschel, 27\u00b052', lateris orientalis regione (frigide) temperata in bambusetis, 3275\u20133350 m, Hand.-Mazz.9238 Taxon classificationPlantaeAsparagalesOrchidaceae\ufeff3.J.D.Ya & D.Z.Lisp. nov.5F97E7EB-BF0A-5454-835B-65DEA37917A4urn:lsid:ipni.org:names:77331173-1Papilionanthemotuoensis is similar to P.uniflora (Lindl.) Garay but differs in having a glabrous pedicel and ovary (vs. glandular-pubescent). Its lateral petals are oblong-ovate (vs. oblong) with irregularly denticulate margins (vs. with undulating margins), truncate apices (vs. obtuse apices). Its labellum is white tinged with yellow (vs. uniformly white), with a subflabellate mid-lobe and a labellum base with an apically dilate to reniform claw, its apex is emarginated with an irregularly denticulate margin .KUN!), plants originally collected from Tibet (Xizang), Linzhi City, Motuo County, 1625 m, at the edge of a subtropical, evergreen, broadleaved forest.China. Yunnan, Kunming, voucher from cultivated plants at Kunming Institute of Botany, CAS, 20 Oct. 2020 (flowering), J.-D. Ya BC201015 County.The specific epithet \u201cP.uniflora: Nepal. Gosain Than, N. Wallich no. 1993 (K001114863!); India, Mao, C.B. Clarke 41790 (K000891405!)Tibet (Xizang), Linzhi City, Motuo County, Bangxin Xiang, 1330 m, from subtropical, evergreen, broadleaved forest. Oct. 2019, M.-K. Li and W. Wang 2019343 . The new epiphytic species was found only in Motuo County, Tibet (Xizang), China, growing on limbs in a subtropical, evergreen, broadleaved forest at elevations of 1300\u20131650 m.Taxon classificationPlantaeAsparagalesOrchidaceae\ufeff4.J.D.Ya, Ting Zhang & Z.D.Hansp. nov.A3D99443-4319-5347-91CF-EE5EC5E27F20urn:lsid:ipni.org:names:77331174-1Gastrochiluslihengiae is similar to G.distichus (Lindl.) O. Kuntze and G.prionophyllus H. Jiang, D. P.Ye & Q. Liu, but can be distinguished from the former by its narrower leaves, blades 0.25\u20130.35 cm wide (vs. 0.4\u20130.6 cm), and distinctly serrate leaf margins (vs. entire), with acuminate and mucronate apices (vs. apex acute bearing 2 or 3 awns). The lateral petals are narrowly oblong (vs. subobovate). The labellum with a hypochile, ca 7.0 mm (vs. 4.0 mm). The outside of the hypochile with three ridges (vs. glabrous), and from the latter by its falcate-lanceolate (vs. ovate) leaves with mucronate apices , the lateral petals are narrowly oblong (vs. subobovate), the central cushion on the epichile of the labellum is not thickened (vs. thickened), while the outer surface of its hypochile has three ridges (vs. glabrous).The floral morphology of KUN! isotype: KUN!)China. Yunnan Province, Nujiang Prefecture, Gongshan County, Cikai Township, 1935 m, in the montane moist evergreen broad-leaved forest, 24 Apr. 2020, J.-D. Ya et al. 22CS21828 . G.distichus: India. Skimm, J.D. Hooker 206. (holotype: K000873754!). G.prionophyllus: China. Yunnan, Malipo County, Xia jinchang town, limestone forest, 1550\u20131650 m a.s.l., epiphytic on tree trunks or on rocks, 15 Mar. 2016, Qiang Liu 359 . G.fargesii: China. Sichuan, Tschen-keou-tin, P.G. Farges 1236 .China. Yunnan Province, Nujiang Prefecture, Gongshan County, Dulongjiang Xiang, 2051 m, in the mixed evergreen broad-leaved forest, 4 Mar. 2023, Ting Zhang et al. 23CS24145 Schltr. in floral morphology, but can be distinguished by its shorter peduncle, ca. 0.3 cm (vs. 1.5\u20132.0 cm), pedicel and ovary ca. 4.5 mm (vs.0.6\u20131.3 cm). Sepals and lateral petals dark yellowish-green with densely purplish-red marks or spots flushed brown to purplish brown (vs. green flushed with brown to purplish brown). The dorsal sepal elliptic, ca 3.4 mm wide , lateral sepals narrowly ovate, ca. 5.5 \u00d7 2.8 mm . Lateral petals narrowly oblong, ca. 5.2 \u00d7 2.7 mm . Labellum with purplish-red spots (vs. yellowish to greenish-yellow marks) and yellowish-green calli (vs. brown to purplish brown) with a transversely oblong epichile (vs. broadly subtriangular) and a green center (vs. deep purple to purplish-brown).KUN!)China. Yunnan Province: Lijiang Prefecture, Yulong County, Yunshanping, 3308 m, in cold-temperate, evergreen conifer forest, 20 May 2020, J.-D. Ya et al. 20CS19022 E.Pritz. and Abiesforrestii Coltm.-Rog. at an elevation of 3300 m a.s.l.The new species is found only in Yulong County, Yunnan, China, and epiphytic on trees of the cold-temperate, evergreen needleleaved forest dominated by G.affinis: India. Sikkim, Lachong Valey, R. Pantling 444 (K000891609!); China. Yunnan, Fugong, Jiakedi, east slope of Gaoligongshan, epiphyticon trunk, alt., 2555 m,16 May 2005, X. H. Jin6984 (PE!); Yunnan, Tengchong, 2828 m, 31 Mar 2007, X.H. Jin 8936 (PE!). G.alatus: China: Yunnan, Fugong, Zhuminglin, 2758 m, 16 May 2005, H.X. Jin 6998 ."} +{"text": "Scientific Reports 10.1038/s41598-023-32484-w, published online 07 April 2023Correction to: Alice\u00a0Dinu was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cS.C.M., C.B, A.D., H.P., and C.S. designed the research. C.D. and A.D. provided the data. S.C.M, C.B. and H.P. analyzed the data. S.C.M and C.B. wrote the manuscript. All authors reviewed the manuscript. Earlier versions of this research were part of the C.B.\u2019s masters thesis which was supervised by S.C.M. and C.S.\u201dAdditionally, in the Data availability section, the OSF repository link was incorrect.https://osf.io/bhaqp/?view_only=629696d6b2854aa9834d5745425cdbbc) to facilitate reproducibility of our work. Data were analyzed using R, version 4.0.0 .\u201d\u201cThe pre-processed data and all analyses codes are available on OSF (now reads:https://osf.io/bhaqp/) to facilitate reproducibility of our work. Data were analyzed using R, version 4.0.0 .\u201d\u201cThe pre-processed data and all analyses codes are available on OSF = Elastic Net. (RF) = Random Forest\"The original Article and Supplementary Information files have been corrected."} +{"text": "Nature Structural & Molecular Biology 10.1038/s41594-022-00769-9. Published online 16 May 2022.Correction to: Proc. Natl Acad. Sci. USA100, 137\u2013142 (2003)); the reference cited twice as 74 in the caption for Extended Data Fig. 10 should have been Leung, M. R. et al. EMBO J. 40, e107410 (2021). The citations and reference list have been corrected in the HTML and PDF versions of the article.In the version of this article initially published, reference 74 was a duplicate of reference 34 (Wargo, M. J. & Smith, E. F."} +{"text": "Juglans) species are used as nut crops worldwide. Eastern black walnut , a diploid, horticultural important woody species is native to much of eastern North America. Although it is highly valued for its wood and nut, there are few resources for understanding EBW genetics. Here, we present a high-quality genome assembly of J. nigra based on Illumina, Pacbio, and Hi-C technologies. The genome size was 540.8\u00a0Mb, with a scaffold N50 size of 35.1\u00a0Mb, and 99.0% of the assembly was anchored to 16 chromosomes. Using this genome as a reference, the resequencing of 74 accessions revealed the effective population size of J. nigra declined during the glacial maximum. A single whole-genome duplication event was identified in the J. nigra genome. Large syntenic blocks among J. nigra, Juglans regia, and Juglans microcarpa predominated, but inversions of more than 600\u00a0kb were identified. By comparing the EBW genome with those of J. regia and J. microcarpa, we detected InDel sizes of 34.9\u00a0Mb in J. regia and 18.3\u00a0Mb in J. microcarpa, respectively. Transcriptomic analysis of differentially expressed genes identified five presumed NBS-LRR (NUCLEOTIDE BINDING SITE-LEUCINE-RICH REPEAT) genes were upregulated during the development of walnut husks and shells compared to developing embryos. We also identified candidate genes with essential roles in seed oil synthesis, including FAD (FATTY ACID DESATURASE) and OLE (OLEOSIN). Our work advances the understanding of fatty acid bioaccumulation and disease resistance in nut crops, and also provides an essential resource for conducting genomics-enabled breeding in walnut.Walnut ( J. nigra L., 2n\u2009=\u200932) is an ecologically important, wind pollinated, fine hardwood , HAD , FATB , and SAD in plastid, and the members of the OLE (OLEOSIN) family , ENR , and FAD in endoplasmic reticulum and KAS I , while genes that were expressed more highly in the third stages of EBW embryo development included OLE , HAD , ENR , and ABCD . We iden14.1280) . The J. s in EBW .J. nigra, J. regia, and J. microcarpa genomes were highly syntenic along each chromosome (J. nigra) with Persian walnut (J. regia) demonstrated eight inversions of more than 600\u00a0kb on chromosomes 1, 3, 4, 8, 10, and 16 (J. nigra) compared to Persian walnut (R genes), including NBS-LRR, myb DNA-binding domain (MYB), and pentatricopeptide repeat (PPR) gene families , while J. regia, V. vinifera, and A. thaliana contain one homolog, i.e. JrNBS-LRR88, located within a 1.2\u00a0Mb region on chromosome 4 , JnNBS-LRR157 (Chr6), JnNBS-LRR221 (Chr7), and JnNBS-LRR303 (Chr11) showed high homology with NBS-LRR gene clusters on the same-numbered chromosomes of J. regia on chromosome 3 is best known as a timber species, although humans have also selected nut varieties of EBW for over 100\u00a0years ,750\u00a0Mb) , C. illi 650\u00a0Mb) , and C. \u00a0Mb , C. 40\u00a0Mb , aJ. nigra) genome were associated with plant hormone signal transduction, vitamin B6 metabolism, pathogenesis , and CYP450 , and PPR gene families among families . Some diR genes) in plants may be involved in the regulation of lipid biosynthesis in J. mandshurica , Chineselissima) , Manchurshurica) , Persianshurica) , little rocarpa) , and Irogillata) . We sele v.2.0.9 . We then v.2.0.9 with a t v.2.0.9 . Species v.2.0.9 . We drewJ. regia , J. manddshurica , J. micrcrocarya ), as weloinensis , using toinensis and Genooinensis . We alsoSparrow\u2019 and ASM2J. nigra genome assembly. We calculated the WGD events using software KaKs_Calculator v2.0 [J. nigra), Persian walnut (J. regia), and V. vinifera. The Ks distributions of orthologues among J. nigra, J. regia, and J. mandshurica, and J. microcarpa, and between walnut genomes and V. vinifera and walnut genomes were determined using the ggplot2 package [Both synteny and synonymous substitution rate (Ks) were used to investigate the timing of whole-genome duplication (WGD) events in the tor v2.0 . We appl package . We iden package .J. nigra versus Persian walnut (J. regia), and EBW (J. nigra) versus J. microcarpa genome assemblies using the online Assemblytics analysis pipeline [J. nigra assembly as reference genome against the J. regia and J. microcarpa genomes using the software Mummer 4.0.0beta2 [J. nigra versus Persian walnut (J. regia), and J. nigra versus J. microcarpa genome assemblies with an E-value cutoff setting of 1e\u22125, and synteny blocks containing at least five gene pairs were identified using MCScanX [J. nigra versus J. regia, and J. nigra versus J. microcarpa was processed by MCScan [We identified the InDels (deletion and insertion) and structure variations (SVs) distinguishing pipeline . We alig0.0beta2 . All-vs-0.0beta2 was perf MCScanX with defy MCScan .J. nigra genotype NWAFU168 , PPR repeat (PPR), Glutamyl-tRNA amidotransferase, subunit A (GATA), cytochrome P450 (CYP450), and NBS-LRR, and identified their members of gene family in 18 species . The sequences of putative PR, PPR, GATA, CYP450, and NBS-LRR genes were used as queries in a BLASTP search against nine protein databases to identify candidate orthologs with parameters E-value <1e-5, identity\u226550% and coverage\u226550% [NBS-LRR genes of J. nigra and J. regia were determined using TBtools software [NBS-LRR members in EBW (J. nigra) and Persian walnut (J. regia) using MEGA software [NBS-LRR126 members in J. nigra and J. regia, we downloaded a total of 20 PR126 members from NCBI , MCScanX . We perflantCARE with theThis work was supported by the National Natural Science Foundation of China , the Operating Services of Qinling National Forest Ecosystem Research Station financed by Ministry of Science and Technology of China, Natural Science Basis Research Plan in Shaanxi Province of China (2019JQ-641), Shaanxi Academy of Science Research Funding Project (2019\u00a0K-06), and Science Foundation for Distinguished Young Scholars of Shaanxi Province (2023-JC-JQ-22). This work was also supported in part by the United States Department of Agriculture Forest Service. Mention of a trademark, proprietary product, or vendor does not constitute a guarantee or warranty of the product by the US Department of Agriculture and does not imply its approval to the exclusion of other products or vendors that also may be suitable.P.Z. and S.Z. conceived and designed the study. F.Y., F.H., and P.Z. collected the samples. F.H., H.Z., and F.Y. took the morphology picture and collected the transcriptome materials of black walnut. H.Z., F.Y., F.H., and P.Z. assembled the genome, and performed gene annotation, gene family, and expression profiles. H.Z., F.Y., M.Y., K.W., H.Y., P.Z., and S.Z. supported the software. F.Y., H.Z., and P.Z. performed the comparative genome analysis. H.Y., H.Z., F.H., and P.Z. performed the population genomic analysis, F.Y. and H.Z. performed the whole-genome duplication and LTRs analysis. H.Z. and P.Z. wrote the draft manuscript and then P.Z., K.W., and S.Z. edited and revised the English writing of this manuscript. All authors contributed to and approved the final manuscript.J. nigra in this study have been deposited in China National GeneBank (CNGB) Nucleotide Sequence Archive database under project accession number CNP0001209 (https://db.cngb.org/search/project/CNP0001209/). The transcriptome data of six tissues and organs and husk, shell, and embryo have been deposited in the NCBI, under accession numbers: PRJNA799697 .The whole genome sequence data including Illumina short reads, Nanopore long reads, Hi-C interaction reads, and transcriptome data have been deposited in the NCBI, under accession numbers: PRJNA801766 (SRR17842367 and SRR17841629). The Illumina whole-genome resequencing data of None declared.Horticulture Research online.Web_Material_uhad015Click here for additional data file."} +{"text": "To the Editor,We thank Vir\u00fa-Loza and Ch\u00e1vez-Nomberto for highlighting some of the limitations and concerns raised in the discussion section of our paper, \u201cSafety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort\u201d , and agrM.M. has received research support from Merck Serono and Pfizer, and has consulted for Ascendis, BioMarin, Ferring, Merck Serono, Novo Nordisk, Pfizer, and Sandoz. M.B.R. has received speaker fees from Mediagnost, Merck, Pfizer, and Sandoz. M.E.G. has a research contract from Novo Nordisk; serves as a consultant for and/or on advisory boards for Adrenas, Eton Pharmaceuticals, Neurocrine Biosciences, Novo Nordisk, and Pfizer; is a member of a data safety monitoring board for Aeterna Zentaris and Ascendis; and receives royalties from McGraw-Hill and UpToDate. E.V. has received research support from Ascendis, OPKO, and Pfizer. W.C. has received research support from Pfizer. R.R. is a past member of the KIGS Strategic Advisory Board and serves as a consultant for Pfizer. A.L. has received speaker fees from Alexion, Kyowa Kirin, Novo Nordisk, Pfizer, and Sandoz. A.C.S.H.-K. is a past member of the KIGS Strategic Advisory Board; recipient of investigator-initiated independent research grants from Novo Nordisk and Pfizer; and has received lecture fees from Merck-Serono, Novo Nordisk, and Pfizer. T.T. has consulted for JCR Pharmaceuticals. H.G.D. has received honoraria for lectures from Ferring, Ipsen, Novo Nordisk, and Pfizer. M.P. is on the advisory board for IPSEN Increlex Registry, Novo Nordisk, and Pfizer France; has received grants from Ipsen, Merck, Novo Nordisk, Pfizer, Sandoz, and Sanofi; and has French institutional public grants from ANR PHRC. A.G. has consulted for Pfizer and received an investigator-initiated independent research grant from Pfizer. R.S. has received independent research support from OPKO, Pfizer, and Sandoz. M.C., R.G., and M.P.W. are employees and stockholders/stock grant holders of Pfizer. L.I., P.E.C., F.D., R.H., and K.A.-W. have nothing to disclose."} +{"text": "SNAC9 affects tomato ripening, and SNAC9 is involved in ethylene and abscisic acid (ABA) metabolic pathways. However, the function of SNAC9 in pigment metabolism in tomatoes remains unclear. This work seeks to discover the mechanism of SNAC9 involvement in pigment metabolism during tomato ripening by establishing a SNAC9 knockout model using CRISPR/Cas9 technology. The results indicated that fruit ripening was delayed in knockout (KO) mutants, and SNAC9 mutation significantly affected carotenoid metabolism. The chlorophyll (Chl) degradation rate, total carotenoid content, and lycopene content decreased significantly in the mutants. The transformation rate of chloroplasts to chromoplasts in mutants was slower, which was related to the carotenoid content. Furthermore, SNAC9 changed the expression of critical genes involved in pigment metabolism in tomato ripening. SNAC9 knockout also altered the expression levels of critical genes involved in the biosynthesis of ethylene and ABA. Accordingly, SNAC9 regulated carotenoid metabolism by directly regulating PSY1, DXS2, SGR1, and CrtR-b2. This research provides a foundation for developing the tomato ripening network and precise tomato ripening regulation.NAC transcriptional regulators are crucial for tomato ripening. Virus-induced gene silencing (VIGS) of Solanum lycopersicum). The complex physiological and biochemical process of tomato ripening includes pigment accumulation, fruit softening, aroma, and flavor development . We thank Yaoguang Liu and Hongliang Zhu for helping with pYLgRNA and pYLCRISPR/Cas9Pubi-H vector.All the authors contributed to the discussion. Y.F. and H.X.K. conceived and designed the experiment; Y.F. performed experiments and data analyses and wrote the manuscript; H.X.K., H.Z.X., and E.C.W. were involved in revising the manuscript; S.Y. and Y.X.Z. collected the literature and revised the manuscript; X.Q.L. measured ethylene release; Y.Z.H. and J.Y.S. checked the language. All authors read and approved the final manuscript.All data related to this manuscript are available in this paper and its supporting materials.None declared.Horticulture Research online.Web_Material_uhad019Click here for additional data file."} +{"text": "The monkeypox epidemic, which became unusually widespread among humans in 2022, has brought awareness about the necessity of smallpox vaccination of patients in the risk groups. The modern smallpox vaccine variants are introduced either intramuscularly or by skin scarification. Intramuscular vaccination cannot elicit an active immune response, since tissues at the vaccination site are immunologically poor. Skin has evolved into an immunologically important organ in mammals; therefore, intradermal delivery of a vaccine can ensure reliable protective immunity. Historically, vaccine inoculation into scarified skin (the s.s. route) was the first immunization method. However, it does not allow accurate vaccine dosing, and high-dose vaccines need to be used to successfully complete this procedure. Intradermal (i.d.) vaccine injection, especially low-dose one, can be an alternative to the s.s. route. This study aimed to compare the s.s. and i.d. smallpox immunization routes in a mouse model when using prototypic second- and fourth-generation low-dose vaccines (104 pfu). Experiments were conducted using BALB/c mice; the LIVP or LIVP-GFP strains of the vaccinia virus (VACV) were administered into the tail skin via the s.s. or i.d. routes. After vaccination ), blood samples were collected from the retro-orbital venous sinus; titers of VACV-specific IgM and IgG in the resulting sera were determined by ELISA. Both VACV strains caused more profound antibody production when injected via the i.d. route compared to s.s. inoculation. In order to assess the level of the elicited protective immunity, mice were intranasally infected with a highly lethal dose of the cowpox virus on 62 dpi. The results demonstrated that i.d. injection ensures a stronger protective immunity in mice compared to s.s. inoculation for both VACV variants. Smallpox (lat. variola) is an especially dangerous infectiousdisease that has claimed lives of many hundreds of millionsof people over the past centuries. During smallpox epidemics,the death toll among the infected people could be as high as30\u201340 %. The variola virus (VARV) is an infectious agent ofthis disease .The VARV was mostly transmitted amongst humans via theairborne or aerosol route during close personal contacts. Theincubation period lasting one or two weeks was followed byabrupt onset of fever, headache, and sacral pain. Several dayslater, rash lesions appeared on the tongue as well as oral andoropharyngeal mucosa; maculopapular rash then developedon the face and hands, subsequently spreading over the entirebody and progressing to pustules. By day 10\u201313 of illness,the pustules reached their maximum size, and then graduallyflattened, dried, and evolved into scabs. By day 30\u201340 of thedisease, the scabs fell off to leave reddish spots. These scabssubsequently left typical deep scars known as pockmarksin some body areas, mostly on the face (the pock-pittedface). Hence, smallpox survivors could be easily phenotypicallydifferentiated from people who had not had this disease.It turned out that smallpox survivors were not susceptibleto it during the later epidemics. Many centuries ago, thisfact apparently gave an idea to Indian and Chinese doctorsto develop a procedure that subsequently became known asvariolation (variola inoculation). According to this method,the infectious material obtained by rubbing scabs taken fromepidemic patients was placed (inoculated) into skin incisions.People infected intradermally typically had a milder form ofsmallpox compared to the naturally occurring smallpox. Afterthe infectious process, a characteristic scar was formed at thesite of VARV inoculation into the skin. This procedure madepeople resistant to smallpox. However, 0.5\u20132.0 % of variolatedindividuals died, so this smallpox protection method has notbecome common .In the XVIII century, a smallpox-like disease in cattle andhorses, which became known as cowpox, was reported in England.This disease was clinically characterized by developmentof skin rashes on animal bodies, most frequently on the udderand teats. The skin elements underwent typical evolutionarytransformation stages (papules to vesicles to pustules); scabsand ulcers were subsequently formed. This infection waseasily transmitted to people who had contacted the infectedanimals. In most cases, cowpox in humans had a mild courseand was characterized by isolated topical lesions, mostly onhands and forearms, at skin microtrauma sites. After infectionresolution, cicatrices resembling variolation scars were formedat former skin lesion sites. Furthermore, people who recoveredfrom cowpox did not get infected during smallpox epidemicsHaving gained this knowledge, an English physicianEd. Jenner inferred that people can be protected against smallpoxby being preliminarily infected with cowpox. Startingwith 1796, he conducted several experimental inoculationsof the infectious material collected from pustules of cowpoxinfectedhumans into skin incisions (the skin scarificationroute) in people and, after some time, infected them withsmallpox using the variolation procedure. In all the cases,people infected with the cowpox were resistant to smallpoxinfection. Ed. Jenner called the developed smallpox protectionprocedure \u201cvaccination\u201d .It is noteworthy that it was not until one century after theinvention of the smallpox vaccination method that the kingdomof viruses was discovered. However, it has only recentlybeen found that different vaccinia virus (VACV) strains thathave been used for immunization for a long time are closestto the horsepox virus rather than the cowpox virus in termsof their genomic organization .Smallpox was completely eradicated by 1977 using masssmallpox vaccination and strict epidemiologic surveillanceunder the World Health Organization\u2019s Global SmallpoxEradication Program .In the overwhelming majority of cases, the VACV wasinoculated for smallpox vaccination by the skin scarification(s.s.) route. This procedure is relatively easy to perform butdoes not allow accurate dosing of the vaccine preparation;therefore, high-dose viral preparation needs to be used toensure reliable immunization .Intradermal (i.d.) injection of the vaccine preparation canbe a modern alternative to the s.s. route. This approach allowsaccurate vaccine dosing and ensures higher immunization reliability,so the dose of the administered vaccine can be reduced,which is especially important in the case of mass vaccination.This study aimed to compare the effectiveness of i.d. ands.s. smallpox vaccination with low-dose VACV in a modelof BALB/c mice. For correct comparison, the VACV wasintroduced by both routes within the same region of mouse tailskin for both procedures. The clonal variant of the LIVP strainand the constructed recombinant LIVP-GFP , which can be regarded asprototypic second- and fourth-generation smallpox vaccines,respectively, were used as study objects.Viruses and cell culture. Clonal variant 14 of the VACVLIVP strain produced by limiting dilution and triple plaquepurification using agarose overlay ,the mutant LIVP-GFP, with inactivated virus thymidine kinasegene, generated based on it , and the cowpoxvirus (CPXV) strain GRI-90 were used in this study. The viruses were grown and titratedusing the African green monkey kidney cells line CV-1 fromthe collection of the State Research Center of Virology andBiotechnology \u201cVector\u201d, Federal Service for Surveillance onConsumer Rights Protection and Human WellbeingAnimals. BALB/c mice were procured from the LaboratoryAnimals Farm of the SRC VB Vector. The experimentalanimals were fed a standard diet with a sufficient amount ofwater, in compliance with the veterinary laws and the requirementsfor the humane care and use of laboratory animals.Animal manipulations were approved by the Bioethics Committeeof SRC VB Vector .Pathogenicity assessment of VACV strains. Three-weekoldBALB/c mice weighing 10\u201312 g were used in the studies to assess the pathogenicity of theVACV LIVP and LIVP-GFP strains upon intranasal (i.n.)infection. Mice preliminarily subjected to inhaled anesthesiawith diethyl ester received 50 \u03bcL of virus-containing fluidat a dose of 107 plaque-forming units (pfu) or normal salineinoculated into the nasal cavity. The animals were followedup for 14 days; clinical signs of infection and animal deathswere documented.The score grading system for assessing the revealed symptomswas as follows: 0 \u2013 no signs of the disease; 1 \u2013 slightlyruffled hair coat; 2 \u2013 significantly ruffled hair coat; 3 \u2013 significantlyruffled hair coat and hunched posture or conjunctivitis;4 \u2013 labored breathing or remaining immobile; and 5 \u2013 death.Each mouse was weighed every two days. The arithmeticmean mouse body weight in each group at each time point wascalculated and expressed as a percentage from the baselinevalue. Data diffusion with respect to the mean value was presentedas standard deviation of the mean and also expressedas a percentage.Immunization of mice. Female BALB/c mice starting withage of 6\u20137 weeks were immunizedby intradermal (i.d.) injection or skin scarification (s.s.) usingVACV LIVP or LIVP-GFP at a dose of 104 pfu.When performing an i.d. injection or s.s. inoculation, theinoculation site was pretreated with 70 % ethanol. Inthe case of i.d. injection, 20 \u03bcL of viral material (104 pfu) ornormal saline (control group) was inoculated according to theprocedure described earlier . Fors.s. immunization, 10 skin incisions were made using a 26Gneedle (0.45 \u00d7 16 mm) within the uppermost layer of epidermis.Viral material (104 pfu) or normal saline (control group)(5 \u03bcL) was immediately applied onto the damaged skin andallowed to be absorbed into the skin.On days 7, 14, 21, 28, 42, and 56 post inoculation (dpi) withthe LIVP or LIVP-GFP viruses, blood samples were collectedfrom the retro-orbital venous sinus in mice according to the procedure described previously.Serum preparations were obtained from individual bloodsamples of mice by centrifuging blood cells. Serum samplesobtained from mouse blood were stored at \u201320 \u00b0\u0421.Enzyme-linked immunosorbent assay of serum samples.Enzyme-linked immunosorbent assay of individual serumsamples of mice was carried out according to the proceduredescribed previously . PurifiedVACV LIVP preparation was used as an antigen. The geometricmeans of log reciprocal titer of VACV-specific IgM andIgG were determined for the study groups, and the confidenceintervals were calculated for the 95 % matching between eachsample and the total population.Assessment of protectivity in immunized mice. On62 dpi, the groups of animals immunized with the LIVP orLIVP-GFP viruses and control animals were i.n. inoculatedwith CPXV GRI-90 at a dose of 46 LD50 (9.4 \u00d7 105 pfu/mouse).The animals were followed up for 14 days, and their deathswere documentedThe data were obtained for groups consisting of six animalsimmunized, either i.d. or by s.s., with VACV LIVP orLIVP-GFP, as well as groups of non-immunized mice andnon-infected animals (the negative control) or animals infectedwith CPXV GRI-90 (the positive control).Statistical analysis. Statistical analysis and comparison ofthe results was carried out with standard methods using theStatistica 13.0 software package .The 50 % lethal dose (LD50) was calculated using the Spearman\u2013Karber method according to the number of animals thathad died . The p-value < 0.05 was consideredstatistically significant.Comparison of the pathogenic propertiesof LIVP and LIVP-GFP strains intranasallyinoculated to miceThree-week-old BALB/c mice were used to assess the pathogenicityof the VACV LIVP and LIVP-GFP strains in thisstudy. The mice were i.n. inoculated with the viruses at a doseof 107 pfu. For VACV LIVP, pronounced clinical manifestationsof the infection were observed starting with 4 dpi; theirmaximum intensity was detected on 8 dpi; and the animalsrecovered after 10 dpi . The disease was accompaniedby significant body weight loss of mice .Under the same conditions, the LIVP-GFP virus withthe mutant thymidine kinase gene caused minimal clinicalmanifestations of infection 6\u20138 dpi and aninsignificant body weight loss in infected animals comparedto those in the control group . I.n. inoculationof mice with the LIVP strain resulted in the death of 50 %animals, whereas all the animals survived the inoculation withthe LIVP-GFP strain .The results demonstrate that VACV LIVP was significantlyattenuated in the case of inactivation of the thymidine kinasegene that had occurred when producing the recombinantLIVP-GFP strain.Comparison of changes in the developmentof humoral immune response to vaccinationof mice with the LIVP and LIVP-GFP viruses over timeAdult BALB/c mice, starting with the age of 6\u20137 weeks, werevaccinated by i.d. injection or s.s. inoculation with low-doseVACV LIVP or LIVP-GFP (104 pfu).Upon i.d. injection of the LIVP virus, significant productionof VACV-specific IgM was observed as early as on 7 dpi; itsmaximum level was reached by 21 dpi, while the IgM titerdropped to the level observed for the negative control groupby 28 dpi and later. Therefore, the results of testing IgM inmouse serum samples are shown in Fig. 3 only for the timepoints of 7, 14, 21, and 28 dpi. Immunization of mice withthe LIVP virus by s.s. inoculation resulted in later and lessmarked IgM production .Both in the case of i.d. and s.s. vaccination of mice withthe LIVP-GFP virus (104 pfu), IgM production was minimal;there were no significant differences compared to the IgMlevel in the control serum samples of non-immunized animals.Much higher titers of VACV-specific immunoglobulins IgGwere produced compared to those of IgM .After i.d. vaccination with the LIVP virus, significant IgGproduction was observed as early as on 7 dpi, reaching its maximum on 21 dpi and remaining at virtually the same leveluntil 28 dpi. The titer of VACV-specific IgG then graduallydecreased by 42 and 56 dpi . For s.s. inoculationof the LIVP virus to mice, synthesis of specific IgG wasdelayed and had lower intensity compared to i.d. immunization.When mice were i.d. inoculated with the LIVP-GFP virus,the IgG production level was considerably lower comparedto that observed after vaccination with LIVP; the productionof these antibodies was maximal on 28 dpi .S.s. inoculation of the LIVP-GFP virus resulted in lowerintensityproduction of analyzed IgG .Assessment of protection against the lethalorthopoxvirus infection in immunized miceIn order to assess how the VACV strains under study, aswell as the i.d. and s.s. vaccine administration routes,affect the development of protective immunity againstorthopoxvirus reinfection in mice, groups of mice immunizedwith the LIVP or LIVP-GFP, as well as control(non-immunized) animals, were i.n. inoculated with CPXVGRI-90 at a dose of 46 LD50 on 62 dpi. The results of theseexperiments demonstrate that only the group of micei.d. immunized with the LIVP virus were fully protected. Inthe group of mice vaccinated with the same virus throughthe s.s. route, 83 % of animals died after being infected withCPXV-GRI .I.d. injection of the LIVP-GFP virus protected 80 % ofmice against reinfection with CPXV-GRI under the sameconditions, while all the mice s.s. inoculated with LIVP-GFPdied . The level of protection against the lethalCPXV infection in mice correlated with the intensity of clinicalmanifestations of this infection .Hence, i.d. low-dose immunization with VACV (104 pfu)used in this study for mice is obviously more effective comparedto s.s. inoculation in the development of protectiveimmunity against heterologous orthopoxvirus infection (thecowpox virus).The large-scale epidemic of monkeypox among humansthat spread to all continents in 2022 has put the question aboutmass vaccination against this infection in the risk groups onthe agenda. Important issues were the need to properly choosethe type of vaccine and the optimal route of smallpox vaccineadministration.The first-generation live smallpox vaccine is a VACVpreparation produced by viral replication in skin of calves orother animals. Recent studies have shown that these vaccinesconsist of a mixture of different VACV variants .In present-day conditions, the VACV vaccine strainsobtained by isolating clonal variants from first-generationvaccines are produced on mammalian cell cultures, and thesepreparations are known to be second-generation smallpoxvaccines . Application of firstandsecond-generation smallpox vaccines for mass vaccinationis currently limited because of the relatively high risk of severecomplications , since the number of compromised people, includingthose infected with HIV, has recently increased.Third-generation attenuated smallpox viruses (havingreduced pathogenicity) are produced by multiple passagesof a certain VACV strain in the cell culture of a heterologoushost. This process is accompanied by emergence of VACVvariants carrying spontaneous deletions and mutations in theviral genome .The novel approach to producing fourth-generationsmallpox vaccines consists in introducing targeted deletions/insertions that disrupt selected viral genes and lead to VACV attenuation by genetic engineering .First-generation live smallpox vaccine based on the VACVLIVP strain is used for smallpox immunization in Russia. TheLIVP strain was produced by epicutaneous passaging of theLister vaccine strain provided by the Lister Institute in rabbits and calves. A preparation of this vaccine is thevirus grown in scarified calf skin . Thepatients receive this vaccine via s.s. inoculation.We used the LIVP strain to produce and characterize theclonal variant of LIVP that can beviewed as a prototype of second-generation smallpox vaccine.The recombinant LIVP-GFP strain with inactivated thymidinekinase gene generated based on it is aprototype variant of fourth-generation smallpox vaccine.At the first stage of this study, we compared the pathogenicitiesof the LIVP and LIVP-GFP strains. The sensitivityof mice to orthopoxviruses significantly depends on their age; therefore, young (3-week-old)BALB/c mice were used in the experiments. The animals werei.n. inoculated with the viruses, since this route imitates thenatural route of infection and ensures the highest sensitivityof mice to this infection .It turned out that after i.n. inoculation of young mice withthe LIVP strain (107 pfu), it induced clinically apparent infection resulting in death of 50 % of animals . Meanwhile, the LIVP-GFP strain led only to mild signsof the disease in mice and complete recovery . Therefore, inactivation of the thymidine kinase gene inLIVP-GFP resulted in its substantial attenuation compared tothe parental LIVP strain, which is consistent with the resultsobtained for other VACV strains .Numerous studies have previously demonstrated that s.s.immunization with second- and fourth-generation VACVbasedvaccines at doses of at least 105\u2013106 pfu fully protectedmice against repeated lethal orthopoxvirus infection .In this work, we studied the feasibility of reducing the doseof prototypic smallpox vaccines to 104 pfu when performings.s. inoculation or i.d. injection to mice. For correct comparison,the VACV was introduced by the s.s. and i.d. routes withinthe same region of mouse tail skin.Adult mice (aged 6\u20137 weeks) with a mature immune systemwere used for studying the immunogenicity of VACV LIVPand LIVP-GFP. The antibody response is known to make themost significant contribution to the development of adaptiveimmune response to VACV vaccination . Therefore, we studied changes in the synthesisof VACV-specific IgM and IgG after i.d. or s.s. vaccinationof mice with the LIVP or LIVP-GFP strains. The results ofthese experiments demonstrated that bothVACV strains ensured more profound antibody productionupon i.d. injection compared to s.s. inoculation. Meanwhile,statistically significant differences in the results between thecompared groups were revealed only for IgG values on 21 dpifor LIVP and 14 dpi for LIVP-GFP. No statistically significant differences in theresults were observed for IgM .In order to assess the level of protective immunity that developedin mice in response to s.s. or i.d. immunization withthe LIVP or LIVP-GFP viruses, these animals were subjectedto i.n. infection with a highly lethal dose of CPXV. It wasconsidered to be the most adequate approach to assessingthe effectiveness of VACV vaccination on the mouse model. Theresults demonstrated that i.d. injection ensured amuch stronger protective immunity compared to s.s. inoculationof the VACV. Only i.d. low-dose immunization with theLIVP strain fully protected mice against the lethal CPXVinfection. The attenuated LIVP-GFP strain did not form asufficiently strong protective immunity under the same conditions.S.s. inoculation with VACV LIVP or LIVP-GFP at theselected low dose did not protect animals against reinfectionwith CPXV .These findings give grounds for inferring that i.d. injection ofboth studied VACV variants induces a much stronger protectiveimmunity in mice compared to s.s. inoculation of theseviruses at the same dose. In addition to more accurate vaccinedosing for i.d. immunization compared to the s.s. route, theformer one is associated with less significant skin damage, thussubstantially reducing the intensity of inflammation reactionthat impedes efficient VACV replication and lowering the riskof bacterial infection at the vaccination site . When using an attenuated fourth-generation vaccinewith reduced specific immunogenicity for smallpox immunization,a higher dose of VACV needs to be used as comparedto that of the second-generation vaccine.The authors declare no conflict of interest.Albarnaz J.D., Torres A.A., Smith G.L. Modulating vaccinia virus immunomodulatorsto improve immunological memory. Viruses. 2018;10(3):101. DOI 10.3390/v10030101.Belyakov I.M., Earl P., Dzutsev A., Kuznetsov V.A., Lemon M.,Wyatt L.S., Snyder J.T., Ahlers J.D., Franchini G., Moss B., BerzofskyJ.A. Shared models of protection against poxvirus infectionby attenuated and conventional smallpox vaccine viruses. Proc.Natl. 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Acta Naturae. 2015;7(4):113-121.DOI 10.32607/20758251-2015-7-4-113-121."} +{"text": "Hyalomma\u00a0detritum, H. excavatum, Rhipicephalus bursa, R. sanguineus, and R. turanicus were identified in this study. Among the five tick species identified here, R. turanicus exhibited the highest infestation rate in both goats and sheep. The presence of Babesia ovis and Theileria ovis based on 18S rRNA was confirmed using molecular assay. The overall MLE of infection rates for B. ovis and T. ovis was 2.49% (CI 1.72\u20133.46) and 1.46% (CI 0.87\u20132.23), respectively. The MLE of B. ovis and T. ovis infection rates in R. bursa was 10.80% (CI 7.43\u201314.90) and 0.33% (CI 0.02\u20131.42), respectively, while that in R. turanicus was 0.12% (CI 0.01\u20130.51) and 2.08% (CI 1.25\u20133.22). This study further confirms that R. turanicus and R. sanguineus can act as vectors for B. ovis, thus advancing our comprehension of tick-borne piroplasmids epidemiology and providing valuable insights for the development of effective control strategies for ticks and tick-borne diseases in Turkey.Ticks play a pivotal role in propagating a diverse spectrum of infectious agents that detrimentally affect the health of both humans and animals. In the present study, a molecular survey was executed of piroplasmids in ticks collected from small ruminants in four districts within Konya province, Turkey. Microscopic examination identified 1281 adult ticks, which were categorized into 357 pools based on their species, sexes, host animals, and collection site before DNA extraction. The infection rates were calculated by using a maximum likelihood estimate (MLE) with 95% confidence intervals (CI). Babesia spp., and Theileria spp., which are conveyed by ticks, serve as the etiologic agents of piroplasmosis that significantly impact the economy of the livestock industry, resulting in production losses, treatment and prevention costs, and increased morbidity and mortality [T. parva and T. annulata cause bovine clinical theileriosis, while T. buffeli, T. orientalis, and T. sergenti are associated with benign theileriosis [B. bovis, B. bigemina, B. divergens, B. major, B. occultans, and B. ovata are confirmed to infect cattle; however, only B. bovis, B. bigemina, and B. divergens are known to cause clinical babesiosis [B. naoakii (Babesia sp. Mymensingh) can cause acute clinical babesiosis in cattle [T. lestoquardi, T. luwenshuni, and T. uilenbergi are considered the pathogenic Theileria spp. causing malignant theileriosis [B. ovis, B. motasi, B. crassa, and Babesia sp. Xinjiang are the causative agents that can induce severe babesiosis [Piroplasms, ortality ,2,3. Babortality . T. parvleriosis . B. bovibesiosis . Moreoven cattle . In smalleriosis ,9. On thbesiosis ,11.Nuttalliella namaqua [Ticks are essential hematophagous arachnid external parasites affiliated with the Ixodida suborder, deemed inferior only to mosquitoes in relevance as carriers of pathogenic entities significantly impacting animal and human health ,13,14,15 namaqua . The pre namaqua ,20. Whil namaqua .Hyalomma, Ixodes, Haemaphysalis, Dermacentor, and Rhipicephalus [Babesia spp. and Theileria spp. in small ruminants in different regions of Turkey [Theileria and Babesia species in ixodid ticks collected from sheep and goats to enhance the understanding of their distribution in Turkey for their effective control.Owing to the unique climatic conditions of Turkey, diverse vegetation, and fertile soil, the country possesses a substantial livestock resource, with small ruminants representing the primary asset and their total population exceeding 56 million in animal numbers ,23. Thescephalus ,30,31,32f Turkey ,34,35,36The sheep and goat owners were duly informed about the research goals, and their consent was obtained before the tick samples collection. All procedures related to tick sampling and subsequent processing were as per the ethical guidelines established by Obihiro University of Agriculture and Veterinary Medicine. .2 (excluding lakes). The average elevation is 1.016 m. Konya\u2019s provincial territory has 60% cultivated and planted areas, 17% forests and heathlands, and 15% meadows and pastures. Konya resembles a big steppe. There is little forest. Konya province has harsh, cold, snowy winters and hot and dry summers. The average annual temperature is 11.5 \u00b0C, and the average relative humidity is 60. The average annual precipitation in Konya is 326 mm. Although only a few districts of Konya close to the Mediterranean region have a slightly Mediterranean climate, the districts of Kad\u0131nhan\u0131, Karatay, Saray\u00f6n\u00fc, and Sel\u00e7uklu , following the guidelines of standard taxonomic keys .Upon microscopic identification, the tick specimens were grouped based on species, sexes, and site of collection, culminating in the formation of 357 pools, with each pool containing 1 to 10 ticks, guided by the sample size. The tick DNA was extracted following the methodology previously described by , using aBabesia and Theileria [AMA-1) of B. naoakii, the 18S rRNA of B. ovis, the merozoite surface antigen (Tlms) of T. lestoquardi, the 18S rRNA of T. luwenshuni, the 18S rRNA of T. ovis, and the 18S rRNA of T. uilenbergi. The PCR cycling conditions for species-specific piroplasmids screening mirrored those previously described, with the only variation being the annealing temperatures, which were adopted from the referenced publications and are elaborated upon in All tick pool specimens underwent initial screening with a universal primer target at the 18S rRNA genes of both heileria , with a \u00ae-T Easy Vector System . Recombinant clones resulting from this transformation were selected for sequencing. The plasmid was extracted from this culture using the Nucleospin\u00ae Plasmid QuickPure Kit (Macherey-Nagel-German), and the sequencing of samples was performed with the Big Dye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems) on an ABI PRISM 3130xl Genetic Analyzer (Applied Biosystems).Selected partial positive PCR amplicons, based on the presence of piroplasmids detected from various tick species, were chosen for sequencing. To ensure adequate concentrations for sequencing, PCR was conducted in larger volumes. PCR amplicons were purified employing a gel extraction kit. . The concentration of eluted DNA was measured using a NanoDrop 2000 spectrophotometer. All PCR amplicons with an adequate DNA concentration were directly sequenced, and samples of low concentration were first cloned into a pGEM vector as per the commercial protocol of pGEMB. ovis (18S rRNA) and Babesia/Theileria (18S rRNA) were prepared using the maximum likelihood method facilitated using MEGA version X software. Bootstrap analysis with 1000 replications was employed to ascertain the confidence of the nodes and branches within the trees. Finally, sequences derived from the current study were submitted to the GenBank of the National Center for Biotechnology Information via BankIt. Statistical analysis was performed in R software, version 4.3.1 . The maximum-likelihood estimate (MLE) of pooled prevalence was calculated using the \u201cPoolTestR\u201d package [Nucleotide sequences garnered in this investigation were aligned with those previously submitted to GenBank via the BLASTn algorithm, facilitating the determination of identities and similarities. Phylogenetic trees for package .B. ovis: OR394130, OR395165, OR395166, OR395167, OR395168, OR395169, and OR395170; for T. ovis: OR395235, OR395236, OR395237, OR395238, OR395239, OR395240, OR395241, OR395242, OR395243, OR395244, OR395245, OR395246, OR395247, OR395248, OR395249, OR395250, OR395251, and OR395252.Sequences derived from this research have been submitted to GenBank and can be accessed using the following accession numbers: for Hyalomma and Rhipicephalus; among these, five species, H. detritum (n = 7), H. excavatum (n = 94), R. bursa (n = 308), R. sanguineus (n = 3), and R. turanicus (n = 869) were from the four districts of Konya province. The heaviest tick infestation in sheep and goats was observed in the Sel\u00e7uklu district, followed by the Kad\u0131nhan\u0131 district. In this study, morphological identification showed that the 1281 ixodid adult ticks gathered from 76 sheep and 29 goats belonged to two genera, H. detritum, H. excavatum, R. bursa, R. sanguineus, and R. turanicus were 0.55, 0.23, 10.69, 0, and 40.59% in goats, and 0, 7.10, 13.35, 0.23, and 27.24% in sheep, respectively , while for T. ovis, it was 1.46% (CI 0.87\u20132.23).Among the 357 tick pools analyzed in this study, 49 pools had piroplasms. R. bursa, R. sanguineus, and R. turanicus were detected that carried Babesia or Theileria in which B. ovis was present in all three species; in contrast, T. ovis was identified only in R. bursa and R. turanicus. The MLE of B. ovis in R. bursa (29/118 pools) and R. turanicus (1/169 pools) were 10.80% (CI 7.43\u201314.90) and 0.12% (CI 0.01\u20130.51), respectively. Due to significant variation in the number of pools for R. sanguineus compared to that of the other two species, the MLE for B. ovis in R. sanguineus pools was not estimated. Furthermore, the estimated MLE for T. ovis in R. bursa (1/118 pools) and R. turanicus (17/169 pools) was 0.33% (CI 0.02\u20131.42) and 2.08% (CI 1.25\u20133.22), respectively.Three tick species, B. ovis was absent in the Kad\u0131nhan\u0131 district but was identified in the other three districts. T. ovis was found in the Kad\u0131nhan\u0131 and Sel\u00e7uklu districts. A detailed distribution of piroplasma detection rates, based on district and tick species, is presented in The presence of piroplasma was noted across all four examined districts. B. ovis 18S rRNA (BoSSUrRNA) gene sequence were constructed. The BoSSUrRNA sequences of B. ovis from R. bursa, R. sanguineus, and R. turanicus, identified in this study, were phylogenetically clustered within the same clade as sheep and tick isolates from Turkey, and sheep and goat isolates from various other countries, including Bosnia and Herzegovina, Iran, Iraq, Spain, Tunisia, and Uganda. However, three sequences exhibited divergent clustering from R. sanguineus and R. bursa in Palestine and Turkey, which formed a separate clade , Egypt (OP389065), India (OM666861), and Turkey . This clade was distinct from T. luwenshuni, T. annulata, B. naoakii, B. ovis, and B. bovis sequences from samples of other countries . A previous study identified R. turanicus, Ha. parva, and R. bursa as the predominant species of sheep and goats in the Black Sea Region of Turkey [R. turanicus as the most prevalent tick species among sheep in Turkey, consistent with our finding. Interestingly, H. excavatum demonstrated a relatively higher infestation rate (7.10%) in our study compared to those conducted earlier [Ha. parva was not detected, possibly attributable to geographical and seasonal variations. Of note, despite the comparable climatic conditions across the four selected districts, the presence of R. turanicus was solely identified in the Kad\u0131nhan\u0131 district. To comprehensively understand the influence of geographical disparities across the remaining districts, in-depth investigations are warranted. Such studies would contribute valuable insights into vector distribution patterns and potential ramifications for disease transmission dynamics.Climatic factors like rainfall, vegetation, altitude, and temperature, along with host availability, influence the distribution trends of ixodid ticks and the spread of tick-borne diseases. . Tick inf Turkey . Ceylan f Turkey reported earlier ,48 and HBabesia species associated with babesiosis in small ruminants are considered B. ovis, B. crassa, B. motasi, and Babesia sp. Xinjiang [B. ovis is particularly pathogenic in sheep and goats [B. ovis in sheep and goats has been reported in various provinces of Turkey [R. bursa, R. sanguineus, and R. turanicus can serve as vectors for B. ovis in this region. This parasite is documented to be carried by R. bursa, R. sanguineus, R. turanicus, Ha. parva, H. marginatum, and H. excavatum [B. ovis was detected in 29 out of 118 R. bursa pools , 1 out of 169 R. turanicus pools , and 1 out of 3 R. sanguineus pools. This observation particularly of B. ovis in R. bursa, is consistent with that of prior studies [B. ovis in R. turanicus and R. sanguineus in Turkey [R. turanicus and R. sanguineus may act as vectors for B. ovis in this country. Moreover, phylogenetic analyses using 18S rRNA gene sequences formed two diverged clades of B. ovis. Further investigation into the genetic diversity of B. ovis is warranted. Molecular diagnostic techniques employed in the study of Babesia species have facilitated the identification of previously unrecognized species, including B. naoakii, implicated in cases of acute babesiosis [B. naoakii was detected in Ha. bispinosa [Ha. bispinosa in Turkey, the transmission of pathogens might be mediated by another tick vector, especially given the absence of the primary vector in the region [The most important Xinjiang ,49,50. And goats , and ovind goats . Althougf Turkey ,35,53,54xcavatum ,55,56,57 studies ,55. Therispinosa . At the e region . ConsequTheileria species have long been a focus of research. T. lestoquardi, T. luwenshuni, and T. uilenbergi are known to cause severe theileriosis, which can harm the health and production of these animals. In contrast, T. ovis is generally considered a non-pathogenic species of Theileria [T. ovis can switch from a benign to a pathogenic state under certain predisposing factors, primarily stressful situations or physiological states, leading to severe theileriosis. [T. ovis, T. luwenshuni, T. uilenbergi, and certain Theileria isolates, such as Theileria sp. MK, Theileria sp. OT1, and Theileria sp. OT3 in small ruminants [T. ovis was identified in the Rhipicephalus ticks, possibly because the primary transmission vector was not collected in this study [T. ovis in R. bursa and R. turanicus pools were 0.33% and 2.08% , respectively. In a prior study from the same province as our tick sampling site, T. ovis was detected in sheep with an infection rate of 21.05% [Rhipicephalus ticks are the vectors for T. ovis transmission in Turkey [Theileria spp., which were not detected in this study, should be explored in future studies to provide more comprehensive information for controlling theileriosis.Due to their varied pathogenic effects on small ruminants, heileria . Howevereriosis. . Therefouminants ,33,61. Cis study . The pref 21.05% , which in Turkey , consistB. ovis has been detected in all developmental stages of R. bursa, demonstrating both transovarial and transstadial transmission capabilities, as previously documented [T. ovis is acquired by the immature stages of R. bursa and transmitted by the subsequent adults [B. ovis and T. ovis in R. turanicus and R. sanguineus. As a result, further research is warranted to delve into the intricate dynamics of B. ovis and T. ovis development and transmission in these tick species.cumented . In contt adults . Hence, B. ovis and T. ovis was confirmed in tick vectors in this province. Furthermore, this study corroborates that R. turanicus and R. sanguineus can serve as potential vectors for B. ovis transmission in this region. This research augments our comprehension of the epidemiology of piroplasmids in tick vectors. This research augments our comprehension of the epidemiology of piroplasmids in tick vectors and is expected to contribute valuable insights toward the development of effective strategies for the control of ticks and tick-borne diseases.In conclusion, we investigated the distribution and prevalence of tick-borne piroplasmids in ticks infesting sheep and goats within the Konya province of Turkey, a region where no previous reports identified tick vectors for such piroplasmids. The presence of"} +{"text": "The results of studies in Quaternary geology, archeology, paleoanthropology and human genetics demonstrate that the ancestors of Native Americans arrived in mid-latitude North America mainly along the Pacific Northwest Coast, but had previously inhabited the Arctic and during the last glacial maximum were in a refugium in Beringia, a land bridge connecting Eurasia and North America. The gene pool of Native Americans is represented by unique haplogroups of mitochondrial DNA and the Y chromosome, the evolutionary age of which rangesfrom 13 to 22 thousand years. The results of a paleogenomic analysis also show that during the last glacial maximum Beringia was populated by human groups that had arisen as a result of interaction between the most ancient Upper Paleolithic populations of Northern Eurasia and newcomer groups from East Asia. Approximately 20 thousand years ago the Beringian populations began to form, and the duration of their existence in relative isolation is estimated at about 5 thousand years. Thus, the adaptation of the Beringians to the Arctic conditions could have taken several millennia. The adaptation of Amerindian ancestors to high latitudes and cold climates is supported by genomic data showing that adaptive genetic variants in Native Americans are associated with various metabolic pathways: melanin production processes in the skin, hair and eyes, the functioning of the cardiovascular system, energy metabolism and immune response characteristics. Meanwhile, the analysis of the existing hypotheses about the selection of some genetic variants in the Beringian ancestors of the Amerindians in connection with adaptation to the Arctic conditions shows the ambiguity of the testing results, which may be due to the loss of some traces of the \u201cBeringian\u201d adaptation in the gene pools of modern Native Americans. The most optimal strategy for further research seems to be the search for adaptive variant Interdisciplinary research is important in examining issues relatedto the role of Beringia as an Arctic land bridge in the settlementof the Western Hemisphere. Unfortunately, the floodingof the lowlands of Beringia by rising sea levels 12,000 yearsago led to the loss of a large number of archaeological sites,including possible human settlements. As a result, the mainhypotheses associated with the history of the peopling of theAmericas are based primarily on a synthesis of archaeological,geological, and biological data from the more accessibleregions of Asia and the Americas . According to one model ofAmerican settlement, ancient people from Northeast Asiamigrated to the Americas via Beringia along an ice-freecorridor in what is now Western Canada, which was createdby melting glaciers at the end of the Pleistocene. Accordingto another scenario, Native American ancestors activelydeveloped the coastal zone and migrated to northwest NorthAmerica along the southern coast of Beringia .However, both of these scenarios appear to underestimatethe more complex role that Beringia played in the settlementof the Americas by human populations .Results of new geochronological studies suggest that the\u201cCanadian Corridor\u201d was blocked by ice during presumedhuman migrations ~15\u201316 thousand years ago and was onlyfreed ~13.8 thousand years ago . Therefore,it seems more likely that the migration route is the northwestcoast of America . Since the melting ofthe glaciers in these territories could have occurred as earlyas 18,000 years ago, the coastal migration route could havebeen developed by the first Americans ~17,000 years ago.At the same time, the results of genomic studies indicate thatthe ancestors of the Native Americans appear to have lived inthe Beringian Arctic for quite a long time and survived the lastglacial maximum there, which terminated ~19,000 years ago. It is assumed that thesepopulations adapted to the harsh conditions of the Far Northwhile living in Beringia, and as the climate warmed, Beringiandescendants migrated to Northwest AmericaDue to the rapid development of DNA sequencing techniques,the genomic approach is widely used in modern research inarchaeology and paleoanthropology. Genetic studies of theindigenous populations of Siberia have shown that the mostancient genetic components, which were present as early as30\u201340 thousand years ago in the most ancient inhabitantsof both southern and northern Siberia, were later lost as aresult of genetic drift and population replacement periods.Thus, genomic analysis of the ancient populations of Siberia hasshown that in Siberia there were several periods of almostcomplete population replacements . Themost ancient Late Paleolithic population of Siberia was replaced20\u201311 thousand years ago by newcomers from EastAsia, resulting in the formation of Siberian populations thatgave rise to the ancestors of both Paleosiberians and NativeAmericans. In the time interval from 11 to 4 thousand yearsago, this population was partially replaced by other groups ofEast Asian origin, which gave rise to the modern populationsof Siberia. Additional gene flows in both directions alongthe Bering Strait were also reported at this time. These flowsaffected the genetic structure of Eskimo and Na-Dene populations.The results of paleogenomic studies have shown that theformation of ancestral populations to ancient peoples ofnorthern Siberia and America could have occurred in a widearea from the Trans-Baikal region to Beringia . Paleogenomic dataindicate that during the Holocene the populations of NortheastAsia werevery dynamic in contrast to the Trans-Baikal populations,which demonstrate genetic continuity from the Mesolithicto the Bronze Age . Evidence was alsoobtained that bearers of the Belkachin archaeological culturein Yakutia can be considered ancestors of the Paleo-Eskimos,who migrated to the Americas about 5\u20136 thousand years ago.Population studies of polymorphism of mitochondrial DNA(mtDNA) and Y-chromosome, which are inherited through thematernal and paternal lineages, respectively, have developed greatly over the past 40 years. The results of molecular datingof the evolutionary age of the mtDNA and Y-chromosomehaplogroups distributed among the modern indigenous populationsof Siberia demonstrate that the most ancient geneticlineages in the south of Siberia belong to the postglacialperiod , while in the northeast ofSiberia their evolutionary age does not exceed 10,000 years.Genetic data for the present-day populations of Siberia arethus inconsistent with archaeological and paleoanthropologicaldata showing the presence of Homo sapiens both in thesouth and in the north of Siberia as far back as 40\u201345 thousandyears ago ,but suggest that due to genetic drift, the most ancient geneticlineages were lost in the modern Siberian population . This assumptionwas completely confirmed by the results of the paleogenomicstudy of the Siberians, which showed, as noted above, that inSiberia there have been several periods of almost completereplacements of the earlier inhabitants .The genetic data obtained thus do not contradict the hypothesisthat, during the last glacial maximum, the Arctic partof Asia and America could have beeninhabited by humansBased on the mtDNA variability data, it has been establishedthat the divergence between the ancestors of the Siberian andNative American populations occurred ~25,000 years ago,the evolutionary age of Native American founding mtDNAlineages is approximately 18.5 thousand years, and theirspread across Americas began ~16,000 years ago . The mitochondrial gene pool of Native Americansis represented by only seven mtDNA haplogroups , the evolutionary age of whichranges from 13 to 20 thousand years ago . All of the Native AmericanmtDNA haplogroups are unique, and for six of them (exceptD4h3a) there are still no analogues found anywhere else inthe world, which means that these haplogroups were formedin deep isolation and, apparently, while living in BeringiaFor the haplogroup D4h3a, a related D4h3b-haplotype wasfound in modern Chinese, which diverged from the commonD4h3 ancestor by ~18.3 thousand years, and the evolutionaryage of D4h3a itself is ~13 thousand years .It is also noteworthy that in all cases (except X2a) the NativeAmerican mtDNA haplogroups are derived from East Asianancestors within haplogroups A, B, C, and D, predominantlydistributed in East Asia. Meanwhile, the area of haplogroup Xis located in Western Eurasia, and therefore the appearance ofhaplogroup X2a in the Beringians (and thus in the ancestorsof the Amerindians) could have happened on the basis of thegene pool of their Upper Paleolithic ancestors, related to thepopulation of Western Eurasia. This follows from paleogenomicdata showing that the Upper Paleolithic populationsof Siberia and Eastern Europe (in the time range from 18 to45.5 thousand years ago) were characterized by approximatelythe same set of mtDNA haplogroups of West Eurasian origin . Thus, it is notexcluded that the mtDNA X-haplotypes, which emerged onthe basis of haplogroup X2a, were also common in the genepool of this ancient population. The age of haplogroup X2ais approximately 13,000 years , and itsrange is limited to northwestern North America only .Haplogroup C4c has a similar geographic distribution andevolutionary age (~14 thousand years) . This appears to indicate thatthe carriers of haplogroups X2a and C4c were among thelast Beringians who populated North America. Around thesame time, but along the Pacific coast, haplogroup D4h3apresumably spread to the south of America . Thus, the results of mtDNA polymorphism studiesindicate that both pathways (both the \u201cCanadian Corridor\u201dand the Pacific Coast of America) may have been used in thesettlement of the Americas.The results of studies of Y-chromosome variability alsoshowed that the male gene pool of Native Americans is characterizedby a small set of genetic lineages \u2013 these are haplogroupsQ-M3, Q-M848 and Q-Z780, widespread among NativeAmericans, as well as the more rare haplogroups C-P39and Q-Y4276, typical of Native North Americans, and haplogroupC-MPB373, found in Native South Americans . The evolutionary age ofthese Y-haplogroups ranges from 15.0 to 21.6 thousand years,indicating that they originated in Beringia. This hypothesis issupported by the discovery of the rare haplogroup Q-L804,related to the Native American haplogroup Q-M3, in populationsof Northwestern Europe . Since the divergence time between these haplogroupsis ~17.3 thousand years, it is assumed that migrations fromBeringia took place not only in the direction of America, butalso in the opposite direction to Europe .In addition, it should be noted that according to mtDNAstudies, very rare haplogroups C1e and C1f, related to NativeAmerican C1 haplogroups , were found inIcelanders as well as in the Mesolithic population of Karelia(Yuzhnyi Oleniy Island) . Thus, these data allow us to believethat in Beringia there was not a brief stop of human populationsthat migrated from the south, but indeed the Beringianpopulations, with their own genetic characteristics and uniquemtDNA and Y-chromosome haplogroups, were formed thereover a long time.The question about the duration of the Beringian Standstillis also of great interest and is regularly studied. One ofthe first genetic studies of this problem concluded that theBeringian Standstill can be estimated at ~15,000 years, if westart from the first discoveries of Homo sapiens remains inthe Asian part of the Arctic ~30,000 years ago and until themoment when the Beringian expansion to America took place,i. e. ~15,000 years ago according to genetic data . M. Raghavan et al. (2015) showed based on theresults of a paleogenomic study that the upper boundary ofdivergence between the ancestors of the Native Americansand East Asians should be considered as ~23 thousand years In that case, the isolation period in Beringia was ~8,000 years. Estimatesof the duration of the Beringian Standstill obtained by usingthe analysis of ancient mitogenomes demonstrated that, givenvarious kinds of uncertainties, the isolation period of the Beringianpopulation could have ranged from 2.4 to 9.0 thousandyears .Such a long stay in Beringia suggests that its population wasquite large in number and subdivided within Beringia . It is assumedthat the western part of Beringia (Chukotka) was inhabited byPaleosiberian populations, while the eastern part of Beringia(Alaska and Yukon) was inhabited in the south by the NativeAmerican ancestors and in the north by a separate group ofancient Beringians who disappeared or were assimilated bynorthern Native American tribes . Both of thesegroups of the ancient Eastern Beringians were very closelyrelated, since they showed the C1b and B2 mitochondrialhaplogroups typical of the Native Americans . Moreover, at present thesehaplogroups are more characteristic of the southern NativeAmerican populations, but in the past they were present inthe north of Eastern Beringia, thus confirming the BeringianStandstill hypothesis .It is likely that during the glacial maximum, the southernpart of Beringia was a refugium, characterized by a fairly mildclimate, rich biota, and therefore quite suitable for settlementof ancient people .According to the results of paleogenomic data modeling,the divergence between the Paleosiberians and the populationthat gave rise to the Beringians occurred approximately24 thousand years ago, but the Upper Paleolithic geneticcomponent was obtained by both populations approximately20 thousand years ago (in the ancient Beringians its fractionwas ~18 %) . Thus, it is assumed thatthe most ancient Upper Paleolithic peoples were actuallypresent in Beringia during the last glacial maximum, andthat the formation of Beringians, including Native Americanancestors, began through interaction with the newcomer EastAsia-related peoples ~20 thousand years ago . In this scenario, the time of existence of the relativelyisolated Beringian population is estimated to be ~5,000 years.A study of Y-chromosome polymorphism in Native Americanpopulations also showed that the duration of the BeringianStandstill may not have exceeded 4,600 years . Thus, the results of genomic studies suggest that theadaptation to the Arctic conditions of the ancient populationsthat took refuge in Beringia may have taken several millennia.According to some genetic studies, it is proposed that the genomesof the Native Americans may contain signals of adaptationto the Arctic conditions, which emerged during theBeringian stage of the Native American ancestors formation,which, as noted above, may have taken a fairly long period oftime . A recentstudy of genomic polymorphism in various contemporarycontinental groups showed that Native Americans harbor atleast 20,424 genetic variants suspected to have originated inBeringia . This is comparable tothe number of genetic variants that distinguish Africans fromnon-Africans. However, there are tens of times less specificgenetic variants in Eurasia. At the same time, group-specificpolymorphisms have not been found at all in Europeans, thusindicating rather intensive inter-ethnic contacts within Eurasia.A study of the influence of adaptive selection on the geneticprofile of Native Americans has shown that the appearance ofAmerican-specific genetic variants is associated with variousmetabolic pathways, but the most important ones are associatedwith the production of melanin in the skin, hair and eyes,as well as cardiovascular function .It should be noted, however, that the most distinct traces ofadaptation to the severe conditions of the Far North have beenrevealed in the gene pools of the Eskimo and Paleo-Asiaticpeoples rather than in those of the Native Americans. Eskimoand Paleo-Asiatic populations also originated in the Asian andNorth American Arctic during the last 5\u20136 thousand years and thus,their periods of adaptation are quite comparable in time to theBeringian population. However, in the next 15 thousand yearsafter their isolation, the Beringians began to occupy moresouthern American territories, and therefore it is unknownto what extent the traces of their ancestors\u2019 adaptation tothe Arctic are preserved in the gene pools of modern NativeAmericans .A number of studies of modern and ancient populations ofthe Far North of Asia and America have found evidence ofgenetic and physiological adaptation of Eskimo and Paleo-Asiatic ancestors to low temperatures and an \u201cArctic\u201d dietbased primarily on the consumption of seafood rich in polyunsaturatedfatty acids (PUFAs) .One of the most striking examples of diet-related geneticmarkers is the \u201cArctic\u201d variant of the CPT1A gene(rs80356779-A) .It is known that the \u201cArctic\u201d variant is widely spread in modernpopulations of the Eskimos, Chukchi, Koryaks, andother peoples of the Sea of Okhotsk region, whose economicstyle is connected with sea hunting .According to paleogenomic data, the earliest records of the\u201cArctic\u201d variant of the CPT1A gene were found among theGreenland and Canadian Paleo-Eskimos ,representatives of the Tokarev culture of the North of the Seaof Okhotsk region and carriers of the LateJomon culture of Hokkaido Island .The appearance of the \u201cArctic\u201d variant of the CPT1A geneis most likely associated with the adaptive response of theFar North indigenous peoples to the \u201cArctic\u201d diet, which ischaracterized by a marked excess of lipids and proteins anda deficit of carbohydratesIn addition, genetic variants associated with carbohydratemetabolism are very frequent in indigenous populations of Northeast Asia. For example, the maximum frequency (52 %)of deletion of the pancreatic amylase gene AMY2A, necessaryfor starch digestion, was found in the Eskimo, Chukchi, andKoryak populations; ~30 % of the indigenous peoples ofNortheast Asia lack this gene . The highfrequency of AMY2A gene deletion in Northeast Asia may beexplained by the deficiency of starch and disaccharides in thetraditional diet of indigenous peoples in the past. A deficiencyin oligosaccharides can also explain the high incidence ofthe inactive sucrose-isomaltase gene (gene SI ) among theindigenous populations of the Far North of Asia and America. In GreenlandicEskimos, glucose homeostasis-related mutations in theTBC1D4 and ADCY3 genes have also been identified, whichincrease the risk of obesity and type 2 diabetes .Thus, genetic changes that occurred in the past due toadaptationto extreme environments, in the current conditions(when there is no carbohydrate deficiency in the diets of theFar North indigenous populations) become harmful, becausethey increase the risk of metabolic and other diseases.Interestingly, in a number of cases, adaptive changes inthe gene pools of Eskimo and Paleo-Asiatic populations arecaused by nonsynonymous substitutions with high pathogenicityindices , nonsense mutationsleading to stop codons or splicing disruption , and whole gene deletions (as inthe case of the AMY2A gene) . It seems likely thatthis kind of fairly profound genetic changes could have beenpreserved in the gene pools of Native Americans if they hadadapted to the Arctic environment in a similar way, involvinga very specific \u201cArctic\u201d diet.There is a suggestion that since the ancient inhabitants ofBeringia migrated first to the sub-Arctic Pacific coast and thenon to Northwest America, they may have practiced a maritimetype of economy at the sub-Arctic stage . But,apparently, this stage of migration history was not reflectedin the gene pools of the Native Americans, or their ancestorsdid not hunt sea mammals, but hunted mainly megafauna:mammoths, bison, horses and other terrestrial animals of theGreat Arctic Plain . In that case, it is assumed that Amerindianancestors had to adapt primarily to vitamin D deficiency,because at high latitudes UV radiation levels are insufficientfor annual synthesis of cholecalciferol D3 in the skin, and theintake of ergocalciferol D2 depends on dietGenetic adaptation to vitamin D deficiency suggests thatthe dietary sources of this substance that are available toArctic peoples were scarceor absent in the Beringian steppe-tundra biome. Vitamin Ddeficiency affects the health of children to a greater extent,and so L.J. Hlusko et al. (2018) suggested that Beringiansadapted to UV deficiency through a V370A substitution inthe ectodyslasin receptor encoded by the EDAR gene. Thismutation is widespread in populations of East and North Asia,as well as in Native Americans. One manifestation of this mutationis associated with an increase in the branching densityof mammary gland ducts, which leads to higher amounts ofvitamin D in breast milk .A recent study of Latin American populations also showedthat genes related to energy metabolism played a crucialrole in population adaptation to the environment of America. The great importance of immuneresponse genes, primarily HLA genes, in adaptive processeshas also been highlighted. Moreover, positive selectionin these genes is recorded in Native Americans at differentperiods of their history, both after the European colonizationof America, which introduced new pathogens, and during theinitial settlement of America at the first contact with endemicpathogens .The hypothesis suggesting the influence of high-latitude UVdeficiency on the genetic features of the ancient Beringiansis based on an additional argument involving the adaptiveselection of the FADS genes variants in Native Americans. The fatty acid desaturase genes FADS1and FADS2 encode enzymes involved in PUFA biosynthesisfrom shorter precursors . It is assumedthat the ancestral A-variants of the FADS genes gave advantagesto human populations that consumed food rich in lipidsand proteins , but later in the Neolithic, after the emergence ofagricultural technology, the D-variants became more common,allowing for a higher rate of synthesis of PUFAs from plantlipids .Studies have shown that FADS genes have been affectedby positive selection for a long time \u2013 for example, in Europethere has been an increase in the frequency of haplotype Dfrom less than 10 % 10,000 years ago to 60\u201375 % at present. However, the exact reasons for theincreased frequencies of the FADS genes variants in certainregions of the world have not yet been established. This is dueto the fact that FADS genes are highly pleiotropic. Associationswere found for FADS1 and FADS2 genetic variants with bloodlipids and other metabolites, various blood cell phenotypes,suggesting a link with cardiovascular function . Besides, metabolic balance with respect to PUFAs andother lipids is very important for brain function, in which theFADS1 gene is actively expressed It has been suggested that the emergence of the D haplotypemay have been due not only to the need to increase theefficiency of PUFA synthesis when there is a deficiency inthe diet , but also contributed to an increasein the brain size . In addition, it was foundthat in Greenlandic Eskimos, FADS genes are involved in theprocesses of adaptation to the cold, as there are links betweengenetic variants and the distribution of body fat and height;and the participation of FADS genes in the regulation of growthhormones is also suggested .Population genetic studies have shown that the ancestralhaplotype A is much more common among the indigenouspopulations of Siberia and America . It has also been found that in Greenlandic Eskimosand Native Americans, the FADS1 and FADS2 genes are underpositive selection, which contributed to an almost completefixation of haplotype A in these populations . Meanwhile, a number of otherstudies on Arctic populations of Siberia and North America (Eskimos)have not revealed the effect of selection on the FADS1 andFADS2 genes .Nevertheless, there is a hypothesis that the original positiveselection signal in the FADS1 and FADS2 genes arose inthe ancient population of Beringia due to the need to adaptto the cold and limited food resources provided by the Arctic. It is assumed that these adaptive geneticvariants have been preserved in the gene pools of the NativeAmericans and Eskimos. However, different combinationsof the FADS genes variants are responsible for the effect ofselection in Arctic and Native American aborigines and inEuropeans . This can be due to differentreasons for the selection of the FADS genes variants in populations.In Europeans it was a shift towards a plant-based diet inthe Neolithic, due to which the D-haplotypes with increaseddesaturase activity were more favorable, and in Eskimos ancestorsit was the emergence of a specific \u201cArctic\u201d diet withvery high PUFA content, due to which maintaining the maximumfrequency of A-haplotypes was more preferable. It ispossible that these FADS variants in Eskimos possess evenlower desaturase activity .Meanwhile, a recent analysis of the FADS genes polymorphismin modern and ancient populations has shown that thewidespread distribution of haplotype A occurred under theinfluence of selection already in the Upper Paleolithic populationsof Eurasia, and therefore in the gene pool of theancient Beringians this haplotype could be fixed quite accidentallyunder the effects of genetic drift . Thus, the adaptive changes of FADSgenes in the Native American ancestors are questioned, andthe hypothesis that the FADS haplotypes inherited from theUpper Paleolithic Eurasians are preserved in the gene poolsof Native Americans looks more likelyAccording to the published data, another example of selectiveadvantages obtained by Native Americans from the ancientinhabitants of Beringia may be related to adaptive changesin the ACTN3 gene . This gene encodesthe protein \u03b1-actinin-3, which is expressed exclusively infast-twitch skeletal muscle fibers. Of the polymorphic loci ofthe ACTN3 gene, the most studied is rs1815739, a mutationin which leads to termination of protein synthesis at aminoacid position 577 of exon 16 (R577X substitution) . This causes a deficiency of \u03b1-actinin-3 in fasttwitchskeletal muscle fibers, which, in turn, can result in adecrease in the speed and power indicators of human physicalperformance . Genetic studies have shownthat the frequency of the 577X allele increases with distancefrom Africa to the north of Eurasia and reaches a maximumin the Native American populations .It is suggested that the advantages of the 577X allele, suchas increased endurance and improved protection against thecold, have contributed to the spread of this mutation .Recent physiological and metabolomic studies have shownthat carriers of the 577XX genotype tolerate cold much betterthan 577RR individuals , which maysupport the hypothesis of selection of the X allele at the initialstage of human expansion into Eurasia .According to this hypothesis, the elevated frequency of the577X allele in some human populations could be related toselection to improve metabolic efficiency and promote dynamicactivities .The high frequency of the 577X allele in Native Americanssuggests that this allele was also widespread in ancient Beringians,ancestral to Native Americans. However, the resultsof analysis of the distribution of the rs1815739 polymorphicvariants in the indigenous populations of northeastern Siberia have shown that thefrequencies of the 577X allele and 577XX genotype werenot the highest in Eurasia . Whilethe frequency of the 577X allele in Northeast Siberia is approximately36 % , the maximumfrequencies of this genetic variant are registered in South Asianand Native American populations \u2013 over 60 % according todbSNP database (www.ncbi.nlm.nih.gov/snp).A recent analysis of geographic distribution of rs1815739variants in modern and ancient populations has shown thatpopulation frequencies of the 577X allele correlate neitherwith geographic latitude nor with temperature . None of the statistical tests used in this study foundevidence of the effect of positive selection for the 577X alleleat high latitudes. Thus, the high frequency of this geneticvariant in Native Americans is most consistent with the effectof genetic drift, possibly occurring in Beringia at the stage oflow size of ancestral population. It is possible, however, thatsome advantages of this genetic variant, namely increasedendurance and resistance to cold, contributed to the increasedfrequency of the 577X allele in Native American ancestors.The results of genetic studies of modern and ancient populationsof Eurasia and America have demonstrated quite convincinglythat the role of Beringia in the settlement of theAmericas is very high. To date, sufficiently reliable estimatesof divergence times between the ancestral genetic lineages thatled to the formation of the various populations of NortheastAsia and the Americas have been obtained. The most probablescenario seems to be that during the last glacial maximum, thepopulation that gave rise to the Native Americans ancestors persistedin Beringia for several millennia . It is assumed that this was a relatively small ) group of people well adapted to high latitudes and cold environments, which is confirmed by the results of genomicstudies of modern Native American populations.Possible traces of adaptation to Arctic environments at thegenomic level are associated with various metabolic pathways\u2013 with melanin synthesis processes, cardiovascular systemfunctioning, energy metabolism, and immune responsegenes .It has also been suggested that the relaxation of negative selectionin a number of protein-coding genes observed in NativeAmericans is also associated with the Beringian stage of populationadaptation . 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Cell. 2020;181(6):1232-1245.e20.DOI 10.1016/j.cell.2020.04.037."} +{"text": "Deep brain stimulation (DBS) has profoundly changed the treatment of Parkinson's Disease (PD). Although the selection of patients for DBS is currently driven by validated criteria,After more than two decades of DBS in PD, the correct identification of the most suitable patients for surgery is still a matter of debate. Any new information aimed at filling the knowledge gap on which PD features are most critical in predicting DBS outcome is of utmost importance,(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.A.R.: 1A, 1B, 1C, 3A.M.F.: 1A, 3B.C.A.A.: 1A, 3B.M.Z.: 1A, 3B.L.L.: 1A, 3B.E.M.: 1A, 1B, 1C, 3B.Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. The authors confirm that informed patient consent was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.Founding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.Financial Disclosures for the Previous 12\u2009Months: A.R. speaking honoraria from Bial and Zambon; travel grants from Chiesi Farmaceutici. M.F. speaking honoraria from AbbVie, Bial, and Orkyn; consultancies for Bial and LVL m\u00e9dical. C.A.A. speaking honoraria from Bial, Zambon, and Lusofarmaco. M.Z. speaking honoraria from AbbVie, Bial, and Medtronic. L.L. speaking honoraria from AbbVie and Bial. E.M. no disclosures to report."} +{"text": "Walsh from the London Tubular Centre, UCL Department of Renal Medicine, University College London, London, UK.Consequently, the following was originally omitted from the Acknowledgements: \u2018K.S. is supported by the Wellcome Trust [110282/Z/15/Z]. K.S. and S.B.W. are supported by the UK Space Agency [ST/X000036/1]\u2019.Additionally, the following was originally omitted from the Author Contributions: \u2018T.W., K.T., S.B., K.S., S.W., G.V., A.C., P.B., M.H., J.J. and N.G. critically revised the manuscript. All authors reviewed and approved the final version of the manuscript.\u2019This has been corrected in both the PDF and HTML versions of the article."} +{"text": "Arenga or forms close to it were distributed in the Eocene of North America and Europe. Records of Metrioxenini (Belidae), which are monophages on these palms, confirm this assumption. A new species, Succinometrioxena andrushchenkoi Legalov, sp. n. from Baltic amber is described. The new species differs from S. poinari Legalov, 2012 in the smaller body sizes, elytral punctation larger than the distances between them, and a rostrum weakly curved in females. It is distinguished from S. bachofeni Legalov, 2013 and S.\u00a0attenuata Legalov et Poinar, 2020 by the forehead lacking horn-like tubercles on either side of the eyes. A description of male of S. poinari was herein compiled for the first time. A list and key to fossil Metrioxenini were given. The modern and fossil distribution of the tribe Metrioxenini and Arenga palms was shown.It has been suggested that palms of the genus In the study of fossil fauna and flora, the situation occurs when either plants or insects are poorly represented in the locality. A striking example is late Eocene amber of Europe, where a huge number of inclusions of various insects were found , while tColeoptera are an important component of both modern and fossil ecosystems. Many of these insects have a well-defined food specialization. Herbivorous insects are divided into poly-, oligo-, and monophages . In paleTrichapion simile indicate the presence of Betula, that of Phytobius leucogaster the presence of Myriophyllum, that of Aizobius sedi the presence of Sedum, and finally that of Hylobius excavatus and of Pissodes insignatus the presence of Larix [Obtaining results from Quaternary studies is the simplest study since these are modern species whose trophic relationships are known. The presence of these species in sediments allows us to confirm the presence of its host plants in that locality. For example, finds of of Larix ,6,7.Ceutorhynchus Germar, 1823 in Baltic and Rovno amber show the presence of Brassicaceae [Oxycraspedus Kuschel, 1955 indicates the presence of Araucaria [Modern species of beetles, as a rule, are absent in the Paleogene and Neogene. Therefore, the reconstruction of vegetation has to be carried out based on the trophic relationships of weevil genera or tribes, which can also be associated with certain plants. For example, the records of some species of sicaceae ,10,11, araucaria in the aArenga Labill. ex DC. palms in the Eocene are discussed based on weevils of the tribe Metrioxenini Voss, 1953 which are obligate herbivores of these palms [Succinometrioxena Legalov, 2012 is described from Baltic amber.In the presented study, the possible presence of se palms ; additioThe studied specimens are deposited in Kaliningrad Regional Amber Museum, Kaliningrad, Russia (KRAM); the Institute of Systematics and Ecology of Animals, Siberian Branch, Russian Academy of Sciences, Novosibirsk (ISEA); Harvard University, Museum of Comparative Zoology, Cambridge, MA, USA (MCZ); the Poinar amber collection maintained at Oregon State University, Corvallis, OR, USA (PACO); Andrzej G\u00f3rski private collection (CAG); Center of Natural History (GPIH); Borissiak Paleontological Institute of the Russian Academy of Sciences (PIN).Succinometrioxena andrushchenkoi Legalov, sp. n., Archimetrioxena zherikhini, Succinometrioxena bachofeni, and S. poinari were taken using a Zeiss Stemi 2000-C dissecting stereomicroscope, and photos of Paltorhynchus narwhal were taken using a Leica M165C binocular microscope. Photographs of Archimetrioxena electrica were received from Ulrich Kotthoff and Eva Vinx (Germany: Hamburg).Photographs of I used previous reports from the literature ,30,31,32The morphological terminology used in this paper follows Lawrence et al. .Fossil Metrioxenini has been described from the three localities: Roan Mountain\u2014USA: Colorado, Garfield County, Green River Formation; lower Eocene, Ypresian, 50.6\u201348 Ma; Baltic amber\u2014Russia: Kaliningrad Oblast, Baltic Sea coast and Yantarnyi quarry near Kaliningrad, Poland: Gda\u2019nsk city area, at the Wisla River estuary, Prussian Formation, upper Eocene, Priabonian, 36.8\u201336.4 Ma; Florissant\u2014USA: Colorado, Rocky Mountains near Pike\u2019s Peak, Florissant Formation; uppermost Eocene, Priabonian, 34.07 \u00b1 0.10 Ma.www.zoobank.org) under LSID urn:lsid:zoobank.org:pub: D03B44CD-D357-4AEE-B982-028E75FE1625Nomenclatural acts introduced in the present work are registered in ZooBank , is 3.6 mm, rostrum length, and 1.1 mm. The body is black, with short, sparse, adpressed setae, appearing silvery-shiny from the presence of a cavity between the specimen and the internal surface of its impression. Rostrum is subcylindrical, quite long, about 1.1 times as long as the pronotum, 7.7 times as long as wide at the apex and in middle, 5.9 times as long as wide at the base, weakly curved, and finely punctate. Head about 0.2 times as long as the rostrum. Forehead wide, about 1.1 times as wide as rostrum base width, depressed, coarsely punctate, with horn-like tubercles on either side. Eyes quite small, rounded, distinctly convex, finely faceted. Vertex is weakly flattened, and densely punctate. Temples about 1.6 times as long as the eye, punctate. Antennae inserted near base of rostrum ventrally, under small convexities. Antennae long, almost reaching the base of the pronotum. The scape and second antennomere are almost teardrop-shaped. Scape 1.6 times as long as wide at apex. The second antennomere is 1.7 times as long as it is wide at the apex, slightly shorter than and about 0.9 times as narrow as the scape. The third\u2013ninth antennomeres are subconical. The third\u2013seventh antennomeres are subequal in width. Third antennomere is about 1.8 times as long as it is wide at the apex, slightly shorter, and about 0.8 times as narrow as the secooonnnd antennomere. The fourth antennomere is about 2.2 times as long as it is wide at the apex, slightly longer than the third antennomere. The fifth antennomere is about 1.6 times as long as it is wide at the apex, about 0.8 times as long as the fourth antennomere. The sixth and seventh antennomeres are subequal to the fifth antennomere. The eighth antennomere is about 1.1 times as long as it is wide at the apex, slightly shorter, and about 1.3 times as wide as the seventh antennomere. The ninth antennomere (first club article) is similar to the eighth antennomere (last article of the flagellum), about 1.6 times as long as it is wide at the apex, about 1.4 times as long, as subequal in width to eight antennomere. The tenth and eleventh antennomeres (second and third club articles) are fused, about 2.0 times as long as the ninth antennomeres. The tenth antennomere is about 1.1 times as long as wide at the apex, about 1.1 times as long, as and about 1.6 times as wide as the ninth antennomere. The eleventh antennomere is slightly shorter than its length, about 0.7 times as long, as and slightly narrower than the tenth antennomere, and weakly acuminate. The pronotum is almost bell-shaped, with a wide apical constriction, 1.4 times as long as it is wide at the apex and the base, about 1.3 times as long as it is wide in the middle, and narrower than the elytral base. The disk is densely and coarsely punctate, with two longitudinal carinae. The distance between the punctures are smaller than their diameter. The sides of pronotum with carinae consisting of obtuse convexities. The scutellum is small and triangular. The elytra are elongated and distinctly convex, about 2.3 times as long as the pronotum, about 2.4 times as long as wide at the base, and at the apical fourth about 1.8 times as long as wide in middle, with two long carinae. The humeri are weakly flattened. Scutellar striole indistinct. Punctate striae regular and distinct near elytral suture, irregular and indistinct in other elytral parts. The punctures are rounded and dense. The distance between the punctures are smaller than their diameter. The interstriae are almost flat. The epipleuron is distinct. The apex of the elytra is separately rounded, obtuse, and without elongated teeth. The margin of the elytra is sharp and carinate. The prosternum is coarsely punctate. The precoxal portion of the prosternum is elongated, 2.7 times as long as the length of the procoxa. The procoxal cavity is round and narrowly separated. The postcoxal portion of the prosternum is short. The metaventrite is about 2.2 times as long as the mesocoxal length, weakly convex, and densely punctate. The abdomen is flattened. The first ventrite is weakly elongated, about 1.4 times as long as the mesocoxal length. The second ventrite is about 0.7 times as long as the first ventrite. The third ventrite is equal to the second ventrite. The fourth ventrite is slightly shorter than the third ventrite. The fifth ventrite is about 1.7 times as long as the fourth ventrite. The legs are long. The metacoxa is transverse. The femora are weakly clavate, rugose-punctate. The trochanter is triangular. The tibiae are almost straight, weakly flattened, and weakly oblique at the apex, with apical dark setose fringes. The tarsi are long, with thick and light setae dorsally. The first tarsomere is triangular. The second tarsomere is widely bilobed. The third tarsomere elongate-bilobed. The fifth tarsomere is elongated. The claws are large, contiguous, and without teeth.Material examined. Holotype, female, KRAM, no. BX 12-23, Baltic amber, late Eocene.Derivation of name. The species is named in honor of K.V. Andrushchenko , who provided the type specimen for description.Diagnosis. The new species differs from S. poinari in the smaller body sizes (3.6 mm), the elytral punctation is larger than the distances between them, and the rostrum is weakly curved in the females. It is distinguished from S. bachofeni and S. attenuata in the forehead without horn-like tubercles on either side of the eyes.Remarks. I saw a specimen of the new species on eBay.Succinometrioxena\u00a0poinari Legalov, 2012 is 3.9\u20134.1 mm, rostrum length 1.1\u20131.2 mm. The rostrum is weakly curved, 1.3 times as long as the pronotum, about 6.7 times as long as wide at the apex and in the middle, densely punctate, with small granulations dorsally. The forehead is wide, flattened, coarsely punctate, and with horn-like tubercles on either side. The eyes are small, rounded, and convex. The vertex is weakly flattened and coarsely and densely punctate. The temples are short, slightly shorter than the eyes, and punctate. The antennae are inserted near the base of the rostrum ventrally, under small convexities, quite long, and almost reaching the base of the pronotum. The first antennomere is almost teardrop-shaped. The second antennomere is oval. The third\u2013eighth antennomeres are subconical. The eighth antennomere is about 1.3 times as long as it is wide at the apex. The ninth antennomere is about 1.1 times as long as it is wide at the apex, about 1.1 times as long as and about 1.3 times as wide as the eighth antennomere. The tenth and eleventh antennomeres are fused. The tenth antennomere is about 1.4 times as long as it is wide at the apex, about 1.6 times as long as, and about 1.3 times as wide as the ninth antennomere. The eleventh antennomere is about 0.7 times as long as wide at the base, about 0.4 times as long as, and about 0.8 times as narrow as the tenth antennomere. The pronotum is bell-shaped. The disk narrowed at the apex and at the base, densely punctate, and with two longitudinal carinae. The elytra are elongated and weakly flattened, 2.6 times as long as the pronotum, and with two long and two short carinae. The carinae and seam have semierect, short, brown setae. The humeri are weakly flattened. The punctate striae are irregular and indistinct. The punctures are rounded, small, and dense. The distance between punctures subequal or smaller than their diameter. The interstriae between the punctures are weakly convex. The prosternum is coarsely punctate. The precoxal portion of the prosternum and elongated, about 1.9 times as long as the procoxal length. The procoxal cavity is round and narrowly separated by the prosternal process. The postcoxal part of the prosternum is short, about 0.6 times as long as the procoxal length. The mesocoxal cavities are rounded, and widely separated. The metaventrite is about 1.7 times as long as the mesocoxal cavity length, weakly convex, and densely punctate. Mesocoxal cavities transverse, narrowly separated. The abdomen is weakly convex, and impressed in the middle. The first ventrite is about 0.8 times as long as the metacoxal length. The second\u2013fourth ventrites are subequal in length. The second ventrite is about 0.8 times as long as the first ventrite. The fifth ventrite is about 1.1 times as long as the fourth ventrite. The legs are long and the femora are weakly clavate, and rugose-punctate. The profemur is thicker than the meso- and metafemora. The tibiae are almost straight, weakly flattened, and weakly oblique at the apex, with an apical dark setose fringe. The tarsi is long, with thick, light, erect setae dorsally. The first tarsomere is conical. The second tarsomere is widely bilobed. The third tarsomere is elongate\u2013bilobed. The fifth tarsomere is elongated. The claws are large, contiguous, and without teeth.Material examined. Holotype, female, ISEA \u2116 2011/1, Baltic amber, late Eocene. Specimens: male, ISEA, \u2116 2023/1, Baltic amber, late Eocene; female, ISEA, \u2116 2016/3, Baltic amber, late Eocene; male, CAG, 4696, Baltic amber, late Eocene.Remarks. This species is fairly common in Baltic amber. I have seen at least 10 specimens on eBay and online stores.Succinometrioxena\u00a0bachofeni Legalov, 2013 .........................................................................21. The first ventrite is strongly elongated B,C. Body\u2013The first ventrite is a little longer than the second ventrite . The bodA. electrica2. The forehead has small horn-like tubercles on either side of the eyes. The pronotum is densely punctated, almost matte .........A. zherikhini\u2013The forehead is simple. The pronotum is sparsely punctated and lustrous .........Succinometrioxena).......................................................43. The sides of the pronotum have obtuse teeth. The forehead usually has horn-like tubercles on either side . ....................................................................7\u2013The sides of the pronotum have no teeth. The forehead is always without horn-like tubercles on either side . . The body (without rostrum) is smaller (3.6 mm).......................................................................................................................S. poinari\u2013The elytral punctation is smaller than the distances between them . The rosS. bachofeni6. The body (without rostrum) is smaller (3.5 mm). The elytra are wider, with small punctation.....................................................................................................................S. attenuata\u2013The body (without rostrum) is larger (6.3 mm). The elytra are narrower, with large punctation......................................................................................................................\u201cP.\u201d bisculcatus7. The body (without rostrum) smaller (3.7 mm) has a subdued sculpture............................................................................................................................P. narwhal\u2013The body (without rostrum) is larger (7.5\u20138.3 mm) with a coarse sculpture .........List of fossil MetrioxeniniPseudometrioxenina Legalov, 2023Archimetrioxena Voss, 1953Palaeometrioxena Legalov, 2012= A. electrica Voss, 1953\u2014Baltic amber [ic amber A. zherikhini \u2014Baltic amber [ic amber Zherichinixenina Legalov, 2009Succinometrioxena Legalov, 2012S. andrushchenkoi Legalov, sp. n.\u2014Baltic amberS. attenuata Legalov et Poinar, 2020\u2014Baltic amber [ic amber S. bachofeni Legalov, 2013\u2014Baltic amber [ic amber S. poinari Legalov, 2012\u2014Baltic amber [ic amber Paltorhynchus Scudder, 1893P. narwhal Scudder, 1893\u2014Florissant [orissant were found in the Albian of the Russian Far East [Pleurambus strongylus Poinar et Legalov, 2014 from the modern tribe Allocorynini Sharp, 1890 was described from early Miocene Dominican amber [The family Belidae Schoenherr, 1826 is a small relict group of primitive weevils ,35,36,37Far East . The triFar East amber haFar East of the fFar East . The triFar East ,27. Pleuan amber . There aArenga [The weevils of the tribe Metrioxenini are confined to the palms of the genus Arenga . Their lArenga , but it Arenga include more than 20 species distributed , Indochina , the Sunda Islands , and the Philippines . Thus, tArenga are not known [Arenga or Iriartea Ruiz & Pav. [Arenga is from the early Eocene of India [Caryota were described from the early Eocene London Clay [Caryota was recorded from the Oligocene of the Isle of Wight [Phoenix eichleri Conwentz, 1886, Palmophyllum kuenowi (Casp. 1872), Bembergia pentatrias Caspary 1881) are known from Baltic amber [Phoenix eichleri belongs to the subfamily Coryphoideae of the tribe Phoeniceae. Palmophyllum kuenowi and Bembergia pentatrias have an unclear taxonomic position. Palms are known from the Green River, including the modern genus Phoenix L. [The earliest finds of the subfamily Coryphoideae Burnett are from the Aptian of North Africa . Reliablot known . Seed frz & Pav. . The earof India and the of India . Seeds pdon Clay . Pollen of Wight . Three pCasp. 187, Bembergoenix L. . Indeteroenix L. .Arenga palms, it can be assumed that fossil representatives developed on the same food plant or genera close to it. Fossil records of Metrioxenini are from the early Eocene of Roan Mountain, Colorado (USA), the late Eocene of Europe , and the terminal Eocene of Florissant, Colorado (USA) . These fArenga in the Eocene was very wide and its species overlapped with Metrioxenini weevil localities. Hopefully, the palm species can be identified during further paleobotanical research.It can be assumed that the range of the genus"} +{"text": "Previously, it was incorrectly identified as A.crassifolia auct. non C.A.Mey. belonging to a distant C3-group of the genus. A phylogenetic analysis based on nrITS and nrETS revealed its position as sister to A.schugnanica (sect. Obionopsis). Both species share aphyllous inflorescence and smooth bract-like cover, but differ in life form, leaves, seed colour, and geographical distribution. We revised native Indian Atriplex species and excluded some of them from the flora of the country. An improved checklist of the native Atriplex species in India with their corrected synonymy and nomenclature is given, and a new diagnostic key is provided.A new subshrubby C Atriplex L. is the largest genus in the Amaranthaceae clade encompassing ca. 260 species distributed mostly in arid regions of the world (Atriplex species in the Indian subcontinent. The latest treatments for the flora of Pakistan (Ali and Qaiser 2001) and India Reichenb., and A.schugnanica is a member of A.sect.Obionopsis (Lange) Dumort. (he world . There ind India counted n region . Subsequ Dumort. . In compAtriplex plants were noted in the year 2021 in Haryana State (India) by one of the authors (NS) of the present paper. Further in situ studies have confirmed an assumption that the specimens cannot be assigned to any known species or their synonyms, and should be described as a new species.Unusual http://www.simplemappr.net).Field studies were carried out in the Haryana State (India). Taxonomic revision of the herbarium material was undertaken in the herbaria BM, CAL , DD, K, LE, MHA, and MW. Distribution map is based on the specimens cited in the text and was prepared using SimpleMappr online tool , 15 accessions were represented by ITS and ETS loci (see below) . Following Halimionepedunculata (L.) Aellen as an outgroup for ITS- and ETS-based molecular phylogenetic analyses. In short, we analyzed 37 ITS and ETS sequences of 19 taxa was extracted from 5\u201310 mg of dried leaves employing the DNeasy Plant Mini Kit , as described in the manual.The DNA from a sample of PCRs were carried out in Thermal Cycler T100 using the primers and cycling protocols summarized in Table The PCR cocktail (20 \u03bcL) contained 1.5\u20132 ng of the total DNA, 5 pmol of each primer, 4 \u03bcL of Ready-to-Use PCR Master mix 5\u00d7 MasDDTaqMIX-2025 containing a \u201chot-start\u201d SmarTaq DNA polymerase .PCR products were purified with the Cleanup Mini BC023S Kit following the manufactured instructions. Sanger sequencing was performed at Evrogen JSC employing PCR primers using the Maximum Likelihood approach . Ten percent of the samples were removed as burn-in. A maximum clade credibility tree was generated using TREE ANNOTATOR v.2.4.5 .India. Haryana, surroundings of Panipat town, near Asan Kalan village, Monoecious subshrub up to 1.5 m high, branched in upper half; leaves alternate, shortly petiolate; petioles up to 1.0 cm long; blades greyish-silvery on both sides, 1.0\u20134.0 \u00d7 0.5\u20131.0 cm , oblong or narrowly oblong, entire or shallowly sinuate, with Kranz-anatomy; inflorescences branched, up to 15 cm long, with pseudopposite bracts or with a few small leaves forming pseudowhorls , aphyllous in other parts; glomerules condensed or slightly interrupted, of both male and female flowers, the latter are also located at the axils of uppermost leaves below the main inflorescence; male flowers stipitate at base, with 5 free perianth segments, anthers 0.25 mm long; bract-like cover of female flowers Fig. rhombic,Flowering: July\u2013November; fruiting: November\u2013December.Atriplexpseudotatarica was observed together with Bassiaindica (Wight) A.J.Scott, Suaedafruticosa Forssk. , and some grasses.Saline soils, sands, wasteland, roadsides, 0\u20132200 m a.s.l. In the natural landscapes in Haryana, A.tatarica L., which also has long aphyllous inflorescences.The specific epithet is chosen due to the resemblance of the new species to Atriplexpseudotatarica, this species is clearly more overlooked than rare. Given that it is often found in disturbed habitats, produces a large number of seeds and is naturally adapted to saline substrates, we propose that the species should be assigned to the IUCN Red List category \u201cLeast Concern\u201d .Afghanistan. [Laghman province] Alingar valley, 6000 ft, 1 Sep 1956, anonymous 23395 (K); [Himachal Pradesh] Kimawar [Kinnaur], 1884, J.R. Drummond 535 (DD-29978); [Haryana], Karnal, 1885, J.R. Drummond 26479 (K); Haryana, surroundings of Panipat town, nr Asan Khurd village, 29\u00b018.1584'N, 76\u00b031.8779'E, 15 Nov 2022, N. Singh & A. Sukhorukov 7 .India. Delhi, 23 Oct 1874, T.T. Thomson s.n. (K); [Punjab] Rawalpindi, 1872, J.E.T. Aitchinson 224 (K); [Gilgit-Baltistan prov.] Skardu, 7000\u20138000 ft, 15 Jul [18]92 [early flowering], without collector\u2019s name 12060 (DD!); Shohdara, 11 Nov 1935 [in fruiting stage], R.R. Stewart 15362 (DD-77925); Lahore, common in weedy places, 17 Oct 1938 [in flowering stage], Parker s3436 ; [Punjab province], nr Attock, 15 Nov 1956, R.R. Stewart 27830 (K).Pakistan. Lahore, 1846, A.pseudotatarica are represented by upper twigs of the plants. They were mostly incorrectly identified as A.crassifolia, or rarely left without identification, as Atriplex sp. To date, the name A.crassifolia may be found misapplied to some other species attributable to different groups of the genus. Atriplexcrassifolia is an annual C3-species belonging to A.sect.Teutliopsis Dumort. (A.crassifolia reported from Europe are erroneous (A.patens (Litv.) Iljin, another species from A.sect.Teutliopsis Dumort.: A.crassifolia has also been widely used for the plants growing in lowlands of India and Pakistan and high mountains. Nevertheless, all records of A.crassifolia from the Himalayas refer to C4-species from A.sect.Obione (Gaertn.) Reichenb.: A.pamirica Iljin and A.schugnanica Iljin , and those from the lowlands and foothills belong to A.pseudotatarica.All examined herbarium specimens of Dumort. with a r Dumort. , penetra Dumort. . All othrroneous . Aellen tliopsis . The spean e.g., , and it an e.g., . Hooker A.pseudotatarica, of which some specimens were misidentified as A.leucoclada Boiss. A.pseudotatarica.Some of the plants growing in the lowlands of Pakistan also belong to Fig. . Based on the combined nrITS and nrETS analyses, A.pseudotatarica was found sister to A.schugnanica, and both form a subclade within the Eurasian clade, A.sect.Obionopsis (Lange) Dumort., which comprises ~ 15 C4-species predominantly distributed in Irano-Turanian floristic region , but have several conspicuous morphological differences 2600\u20134800 m a.s.l. are present in the lowlands of Pakistan, and only one (A.pseudotatarica) is reaching India. Atriplextatarica, widely distributed in many parts of the \u201cFlora Iranica\u201d area, as well as A.kalafganica Aellen has been provided by A.amnicola Paul G.Wilson, A.nummularia Lindl., A.lentiformis (Torr.) S.Watson Boiss. Boiss. and annusifolia\u201d . Atriple4 leaf anatomy. No C3Atriplex species were recorded in India. The alien species are not included in the key because their taxonomy and alien status have not been fully evaluated.All native species have the CAtriplexcentralasiatica Iljin, Act. Inst. Bot. Ac. Sci. USSR, ser. 1, 2: 124 (1936).1. Holotype. [KAZAKHSTAN] Lac. Balchasch, prope Aczie , 19 Sep 1930, E. Czerniakowska 819 (LE!).This species was reported from India for the first time by Atriplexpamirica Iljin, Acta Inst. Bot. Ac. Sc. USSR, ser. 1, 2: 124 (1936).2. Atriplextataricavar.pamirica (Iljin) G.L.Chu in Kung & Tsien, Fl. Reipubl. Pop. Sin. 25(2): 46 (1979), nom. inval. (Art. 41.5).\u2261 Holotype. [TAJIKISTAN] Khargosh, in ripa lac. Kara-kul [bank of Kara-kul Lake], 30 Jul 1878, Yu. Ashurbaev s.n. (LE!).A.tatarica and A.pamirica occupy distant positions on the molecular tree (A.sect.Obionopsis (Lange) Dumort. and A.sect.Obione (Gaertn.) Reichenb., respectively .3. Atriplexrepens Roth, Nov. Pl. Sp.: 377 (1821).4. Obionerepens (Roth) G.L. Chu, Gen. New Evol. Syst. World Chenopod.: 165 (2017). Neotype .\u2261 Obionenummularia Moq., Chenop. Monogr. Enum.: 72 (1840).= Obionekoenigii Moq. in DC., Prodr. 13(2): 109 (1849), nom. illeg. superfl. Holotype: INDIA. \u201cEx India orientali\u201d, J.P. Rottler s.n. .\u2261 Atriplexkoenigii Wall., Numer. List: no. 6951 (1832), nom. nud.\u2013 Atriplexrepens B.Heyne in herb.\u2013 Note. The name Obionenummularia Moq. was validly published on the basis of the only specimen (holotype) originating from India, J.P. Rottler s.n. collected in the late 18th century and received by A. de Candolle under the name \u201cAtriplexcristata Koenig\u201d from M.N. Puerari (now at G-DC).A.repens on Hainan Island (southern China); however, the latter species is distributed in the coastal areas in southern India and Sri Lanka. The correct name for the plants growing in Hainan and other parts of tropical China as well as in southern Japan is A.maximowicziana Makino.Atriplexschugnanica Iljin, Acta Inst. Bot. Acad. Sc. URSS, ser. 1, 2: 123 (1936).5. Chenopodiumpallidum Moq., Chenop. Monogr. Enum.: 30 (1840), nom. rejic. prop.= Atriplexpallida (Moq.) Sukhor., Phytotaxa 226(3): 288 (2015). Lectotype . Image of the lectotype available at: https://science.mnhn.fr/institution/mnhn/collection/p/item/p04993339\u2261 Lectotype. .Note. The name Chenopodiumpallidum Moq. was proposed for rejection by Atriplexstocksii Boiss., Diagn. Pl. Orient., ser. 2, 4: 73 (1859).6. Atriplexgriffithiivar.stocksii (Boiss.) Boiss., Fl. Orient. 4: 916 (1879).\u2261 Atriplexgriffithiisubsp.stocksii (Boiss.) Boulos, Nordic J. Bot. 11(3): 310 (1991). Lectotype .\u2261 Obionestocksii Wight, Icon. Pl. Ind. Orient. 5(2): 5, tab. 1789 (1852). Lectotype (designated here): [PAKISTAN] Scinde [Sindh prov.], J.E. Stocks 452 .= Notes. The species was originally described as Obionestocksii Wight based on a single specimen, J.E. Stocks 452, collected in present-day Sindh Province of Pakistan. Atriplexstocksii based on two collections by Stocks from Pakistan and one from southern Iran, Aucher-Eloy 5268. In the protologue of A.stocksii, Boissier cited the type collection used by Wight but employed the same species epithet. For this reason, the protologue of his species name included the type of Wight\u2019s species but Boissier\u2019s species name cannot be treated as illegitimate. Boissier explicitly described his species as new and validly published its name in its own right, without any presumed basionym; for this reason, this species name has no basionym even though the potential basionym exists. As Boissier\u2019s species name is not superfluous, it cannot be automatically typified by the type of Wight\u2019s species name.A.stocksii Boiss. is the specimen kept at G-DC, which belongs to the same gathering as the type of O.stocksii Wight. The later type designation with the specimen at K, which was made by The species is reported from Gujarat and Tamil Nadu States , but in Atriplexcrassifolia C.A.Mey. Occurs only in Kazakhstan, Russia (South-West Siberia), and western China (Xinjang). Reported by many old and recent authors (see above).1. Atriplexlaciniata L. European coastal plant. Previously reported by 2. Atriplexsagittata Borkh. (= A.nitens Schkuhr). Species native to temperate regions of Eurasia. Previously reported by A.nitens).3. Atriplexrosea L. Reported by 4."} +{"text": "R. gallica in comparison with R. subcanina. R. gallica was chosen because it is still unexplored in terms of various bioactive substances and is strongly present in Slovenia. Given that roses are generally very variable and unstudied, our research will contribute to greater transparency and knowledge of the bioactive composition of rosehips and petals. We found a strong positive correlation between the total content of phenolics and ascorbic acid, between the total content of organic acids and the total content of carotenoids, and between the total content of sugars and the total content of organic acids. Hips of R. gallica contained higher amounts of sugars, ascorbic acid, and carotenoids than R. subcanina. Based on the composition of phenolic compounds in the petals, it is possible to distinguish between the two species. Among all the phenolic compounds in the petals, both genotypes are richest in gallotannins, followed by flavonols. Among anthocyanins, cyanidin-3-glucoside was determined, the content of which was also higher in R. gallica. It can be concluded that the studied hips had an extremely low sugar content and, consequently, an extremely high organic acid content. The content of carotenoids in hips was in the lower range of the average content compared to data from the literature. By optimizing the harvesting time, we could obtain a higher content of carotenoids, which could potentially be used for industrial purposes. However, we found that the analyzed petals were a rich source of phenolic compounds, which benefit the human body and could be potentially used in the food and cosmetic industries.Our research aimed to investigate the primary and secondary metabolites of rosehips and petals of Rosa, where considerable diversity exists within and between species. They are characterized by their ability to germinate everywhere and are perfectly adapted to pioneer conditions, where there are almost always extreme growing conditions. They also grow in climatic vegetation communities, except they occupy different places and may not be as lush there. As an ornamental plant, roses have been common throughout the world since time immemorial. Rosehips, a rich source of bioactive compounds beneficial to humans, are becoming increasingly prominent [Roses belong to the genus rominent ,2.R. gallica is very interesting since it is the most widespread European species and the parent species for several cultivars [Functional foods or dietary supplements that protect humans from oxidative stress and many diseases have recently become increasingly popular. Roses are used for various purposes, including protecting health and treating influenza, infections, inflammatory diseases, and chronic pain. In addition, they have beneficial effects on skincare and healing ulcers. They are also used in foods and beverages, such as tea, jams, and jellies. They have recently been used as an ingredient in probiotic drinks, yoghurts and soups as dietary supplements. They are known to be antioxidant, anti-inflammatory and antibacterial, to improve the immune system, and assist against respiratory, gastric, and intestinal problems. In relation to these properties, several main species of roses are essential. Among them, ultivars ,4.R. gallica petal extract promoted skin whitening and anti-wrinkle effects by regulating intracellular signaling, supporting its usefulness in cosmetic products for skin whitening. In addition, Jo et al. [R. gallica is promising for use as a functional ingredient in developing antiaging nutraceuticals. Ueno et al. [R. gallica in male mice exposed to chronic stress and those under normal conditions. When the mice were exposed to stress, R. gallica had an anti-stress effect. They concluded that R. gallica has the potential as a medicinal plant that prevents stress. The medicinal effects of R. subcanina are also widely known and confirmed. Their effects are similar to those of R. canina, about which we found several studies and which is accepted as a control species in the Rosa genus. Tumbas \u0160aponjac et al. [R. canina extract positively affects the respiratory activity of neutrophils. Ashtiyani et al. [R. canina fruit extract protects against renal dysfunction, oxidative stress and histological damage.Song et al. demonstro et al. concludeo et al. studied c et al. confirmec et al. reportedi et al. concludeR. dumalis and R. rubiginosa were glucose and fructose. Demir et al. [R. gallica, R. canina, R. dumalis, R. gallica, R. dumalis subsp. boissieri and R. hirtissima. They also determined glucose and fructose as the main sugars. The highest content was determined in R. canina and R. gallica. They concluded that there were no great differences in the content of analyzed sugars. Rosus et al. [R. subcanina. They found great qualitative and quantitative variability among the analyzed genotypes. Adamczak et al. [R. canina, R. dumalis, R. glauca, R. inodora, R. jundzillii, R. rubiginosa, R. sherardii, R. tomentosa, R. villosa and R. zalana. They found that the citric acid content was, on average higher than the ascorbic acid content. They also confirmed that there is great variability among genotypes. Javanmard et al. [R. canina species from Iran. Demir et al. [Uggla et al. found thr et al. studied s et al. reportedk et al. studied d et al. reportedr et al. determinr et al. , who lisr et al. ,17. Olssr et al. concludeR. pendulina, R. spinosissima and their hybrid R. pendulina \u00d7 spinosissima (R. reversa). They found that out of 28 different phenolic compounds identified, quercetin-3-glucuronide was only present in the petals of the hybrid. The highest content of total phenolics was found in R. spinosissima. Cunja et al. [Rosa canina, Rosa glauca, Rosa rubuginosa and Rosa sempervirens, as well as three modern cultivars \u2018Rosarium Uetersen\u2019, \u2018Ulrich Brunner Fils\u2019 and \u2018Schwansse\u2019. They found seven different anthocyanins and thirty-one flavonols, as well as 14 phenolic acids and their derivatives, 15 flavonols and 20 tannins. Cendrovski et al. [R. rugosa petals are a rich source of phenolic compounds, which determine their antioxidant properties. The main polyphenolics were ellagitannins, accounting for 69 to 74% of all petal polyphenolics. Four other anthocyanins were identified: cyanidin 3,5-di-O-glucoside, peonidin 3-O-sophoroside, peonidin 3,5-di-O-glucoside and peonidin 3-O-glucoside, of which peonidin 3,5-di-O-glucoside accounted for approximately 85% of all anthocyanin compounds identified. Cunja et al. [Rosa species. They listed gallic acid, caffeic acid, chlorogenic acid, p-coumaric acid, rutin, apigenin, cinnamic acid and quercetin.Kunc et al. studied a et al. reportedi et al. reporteda et al. reportedR. gallica compared to R. subcanina, which, although not as common as some other wild roses, is also found in Slovenia. R. gallica was chosen because it is still unexplored in various bioactive substances and is strongly present in Slovenia. Our analyses are based on the research of Kunc et al. [R. gallica, compared to R. subcanina, are a rich source of bioactive compounds that could potentially be used in the food industry, alternative treatments, and cosmetic preparations.Our research aimed to investigate the primary and secondary metabolites of rosehips and petals of c et al. , who anaR. gallica and that of R. subcanina. The dominant sugar was fructose, followed by sucrose in R. gallica and glucose in R. subcanina. Sorbitol was present only in R. gallica. The differences between the individual sugars were also not significant.The total sugar content is shown in R. subcanina than in the hips of R. gallica. The hips of both genotypes had the highest content of quinic acid, the hips of R. gallica 44.07 g/kg FW and the hips of R. subcanina 55.11 g/kg FW. The second highest content in the observed hips was citric acid. Shikimic acid and fumaric acid were present in lower amounts. The fumaric acid content was slightly higher in R. subcanina than in R. gallica.The total organic acids content was signR. gallica (5.39 g/kg FW) than in the hips of R. subcanina (1.17 g/kg FW).The content of ascorbic acid was signR. gallica, with 32.39 mg/100 g FW and in those of R. subcanina, with 28.27 mg/100 g FW than in the hips of R. subcanina (5305.45 mg/kg FW) of phenolic compounds than those of R. subcanina (1263.08 mg/kg FW). The main phenolic groups determined in the pulp with skin and in the seeds of hips of the studied rose genotypes were hydroxybenzoic acid derivatives (HBA), hydroxycinnamic acid derivatives (HCA), gallotannins, ellagitannins, flavanols and flavonols. Flavones were present only in the pulp with skin. Dihydrochalcones were detected only in the seeds. In R. subcanina, flavanols predominated in the pulp with skin (3608.40 mg/kg FW) and the seeds (483.07 mg/kg FW). In R. gallica, flavanols were the dominant group in the pulp with skin, with 12,293.14 mg/kg FW, while dihydrochalcone was predominant in the seeds, with 1098.45 mg/kg FW. Cyanidin-3-glucoside was also identified in the pulp with skin of R. subcanina and in the seeds of R. gallica.The total content of phenolic compounds in the pulp with skin was significantly higher in the hips of g/kg FW) . HoweverBased on the correlation test, a strong positive correlation was found between total phenolics content (TPC) and ascorbic acid (AC), between total organic acids content (TOC) and total carotenoids content (TCC) and between total sugar content (TSC) and TOC .R. gallica and R. subcanina. The first and second components of the PCA model for the total data accounted for 81.7% of the total variance. It can be seen that the samples belonging to the same genotype are close to each other. This means the substances used to distinguish between the two species were appropriately used. The TPC and AC analyses significantly describe the samples of R. gallica, while the TCC and TOC analyses better describe the samples of R. subcanina. TSC analyses are not significant for either R. gallica or R. subcanina samples.Principal component analysis (PCA) of all samples and metabolites was performed to provide a comprehensive picture of the analyses of rosehips (pulp with peel) in our study . PCA shoR. gallica than in R. subcanina .The total content of phenolic compounds in rose petals was highR. gallica (73.87 mg/kg FW) than in R. subcanina (19.56 mg/kg FW). Caffeoylquinic acid was present only in the petals of R. gallica. There was a statistically significant difference between the samples studied. The content of gallotannins was higher in R. subcanina, 28,519.34 mg/kg FW. In R. gallica, the content of gallotannins reached 18,838.37 mg/kg FW. The predominant gallotanin was trigalloyl hexoside 1. There was a statistically significant difference between the total content of gallotonins. There is also a statistically significant difference between the content of ellagitannins in our samples. Their content in R. gallica was 884.29 mg/kg FW and in R. subcanina 165.23 mg/kg FW.The content of hydroxycinnamic acid (HCA) derivatives was highR. gallica and 1160.07 mg/kg FW in the petals of R. subcanina. The flavanol with the highest content in both studied roses was the dimer PA monogallate 1. The lowest value was found for epicatechin. The content of flavonols was significantly higher in the petals of R. gallica, 22,260.95 mg/kg FW, while in R. subcanina, it was only 5609.20 mg/kg FW. Petals of R. gallica had the highest content of quercetin dihexoside 2 (6624.44 mg/kg FW), which was not present in the petals of R. subcanina\u2014in petals of R. subcanina, quercetin-3-arabinofuranoside dominated, with a content of 2541.73 mg/kg FW. Dihydrochalcone phloridzin was found only in the petals of R. gallica, in which its value reached 1084.44 mg/kg FW.There was a statistically significant difference between the total content of flavanols and flavonols in the rose petals . The conR. gallica and R. subcanina , which is 37% FW in our case. The total sugar content was thus 2.26 and 3.5 g/kg DW. Cunja et al. [R. canina were between 0.26 and 0.48 g/kg DW. Our samples thus had higher sugar contents. The increase in sugar content may be due to higher altitude and greater drought stress than the samples studied by Cunja et al. [We determined the content of primary and secondary metabolites in the hips and petals of the not yet well-studied rose genotype k et al. determink et al. . The suck et al. . It was k et al. noted, sk et al. . Similark et al. , who stuk et al. and Aback et al. were grok et al. and are k et al. , where tk et al. and RosuR. canina and R. rubiginosa ranged from 46.2 g/kg to 73.2 g/kg FW. Okatan et al. [R. canina was between 15.9 and 22 g/kg FW. Quinic acid, the most available acid in our experiment (44.07 and 55.11 g/kg FW), ranged from 48 to 72 g/kg FW in their samples. Quinic acid was also the most available organic acid in the hybrid R. pendulina \u00d7 spinosissima (48.8 g/kg FW), while the content of this acid in the original species R. pendulina was only 0.29 g/kg FW in the experiment mentioned by Kunc et al. [Organic acids were citric, malic, quinic, shikimic and fumaric. It can be seen that the total acid content in our samples was higher than that in the literature. Cunja et al. reportedn et al. reportedc et al. , the maic et al. reportedc et al. . Namely,c et al. reportedc et al. .R. gallica and 1.17 g/kg FW for R. subcanina. Comparing our results with the results of an experiment conducted by Rosus et al. [R. rubiginosa to 6.2 g/kg FW in R. caesia. Alp et al. [R. dumalis genotypes. The content ranged from 4.02 to 5.11 g/kg FW. In previous studies, the ascorbic acid content in rosehip fruits has been quite variable, with a range of 1.80 to 9.65 g/kg FW [R. canina from Transylvania. They found that the ascorbic acid content of frozen samples grown at 1250 m above sea level was 3.6 g/kg, and of those grown at 440 m was 1.12 g/kg of frozen pulp. They found a good correlation between ascorbic acid content in rosehips and altitude. The site\u2019s altitude in our experiment is about 500 m above sea level, and the ascorbic acid content is even lower than that found by Roman et al. [R. pendulina \u00d7 spinosissima was 10.45 g/kg FW, which is almost twice that in R. penduline, with 5.30 g/kg FW. Our experiment found that the ascorbic acid content of the two genotypes we studied was very similar to the content measured in R. pendulina in an experiment described by Kunc et al. [R. canina, and found that the content of the above acid was 3.85 g/kg FW, the lowest of all the rosehips studied. The highest content (7.4 g/kg FW) was determined in R. rugosa \u2018Rubra\u2019.The content of ascorbic acid Is highly dependent on a variety of factors. The most Important are cultivar, stage of ripeness, altitude etc. The content of ascorbic acid in our samples was 5.39 g/kg FW for s et al. , we notep et al. determin g/kg FW ,38,39,40 g/kg FW reportedn et al. reportedc et al. . Medveckc et al. studied R. gallica and R. subcanina samples. Total carotenoid content was higher in R. gallica than in R. subcanina. Alp et al. [R. dumalis genotypes ranged from 47 to 85 mg/100 g FW. Rosus et al. [R. subcanina was 34.95 mg/100 g FW. In our samples, \u1e9e-carotene was present in the largest proportions (23.37 and 27.56 mg/100 g FW). Zhong et al. [R. rubiginosa, R. multiflora, R. virginiana and R. rugosa. They found a large difference in carotenoid composition among the roses. R. virginiana had the most diverse carotenoid composition and the highest carotenoid content. It was found that the group of lycopene together with \u1e9e-carotene accounted for 28 to 54% of the content of all carotenoids. Medveckiene et al. [Five carotenoids were determined in p et al. found ths et al. reportedg et al. studied e et al. reportede et al. , 0.23 toe et al. . BecauseR. gallica (15.8 g/kg FW) compared to R. subcanina (5.31 g/kg FW). The total content of phenolic compounds in seeds was 1.27 g/kg FW in R. subcanina and 1.71 g/kg FW in R. gallica. Considering how low the sugar content determined in the samples was, the lower content of phenolic substances in the samples of R. subcanina, compared to R. gallica, is also logical. Flavones were determined only in the fruit pulp with skin and dihydrochalcones in the seeds. Najda and Buczkowska [Rosa spp. Varied between 0.3 g/kg and 14 g/kg. Unlike the aforementioned studies, much higher values are reported by Demir et al. [R. dumalis subs. Boissieri was 52.94 g/kg and in R. canina 31.08 g/kg.Total phenolics content in pulp with skin was extremely high in czkowska investigr et al. , who fouR. gallica compared to only 31 in R. subcanina. Cunja et al. [R. canina, also determined 31 different phenolic compounds in this species, morphologically very similar to R. subcanina. Cendrowski et al. [R. rugosa petals identified by UPLC-ESI-MS. Ellagitannins represented the major fraction, accounting for 69 to 74% of petal polyphenolics. In our samples, gallotannins dominated in R. subcanina, accounting for up to 81% of the phenolic compounds identified. In R. gallica, flavonols dominated, with a proportion of 47%, immediately followed by gallotannins with 40%. In contrast to Cendrowski et al. [R. subcanina and 46.9 g/kg FW for R. gallica. In comparison with the research results of Kunc et al. [R. pendulina, R. spinosissima and their hybrids, we found that the petals of R. gallica and R. subcanina had much lower values than those of the aforementioned roses. Of the flavonols, Cunja et al. [R. gallica that we analyzed. In R. subcanina, we could not determine catechin and procyanidin dimer 3 and procyanidin trimer 1. Cunja et al. [R. gallica, they accounted for 82% and in R. subcanina, 73% of the total flavonols. Schieber et al. [R. damascena. In our samples, it was the most abundant of the flavonols. Its contents were 0.36 g/kg FW in R. gallica and 0.25 g/kg FW in R. subcanina. Wan et al. [R. damascena cultivars. Comparing the results of our two genotypes, it can be seen that we also identified the mentioned compound in our samples, but its content was not dominant. The content of the anthocyanin cyanidin-3-glucoside in our two genotypes was 0.18 g/kg FW and 0.04 g/kg FW (R. subcanina). Considering the flower color, the low anthocyanin content in the petals of R. subcanina was expected. Kunc et al. [Echium amoenum), an annual herb native to the Mediterranean region, an excellent source of anthocyanins and used in various forms because of its biological activity. The dominant anthocyanin was cyanidin-3-glucoside, ranging from 0.03 to 1.13 g/kg. Li et al. [Lilium brownii, with a cyanidin-3-glucoside content of 0.106 mg/100 g, and Ipomoea cairica 0.109 g/kg, were highlighted as those with lower contents. The highest contents were recorded for Jatropha integerrima 6.41 g/kg and Pelargonium hortorum 4.97 g/kg.We determined 53 phenolic compounds in the petals of a et al. , who stui et al. determini et al. , Kumar ei et al. , Veliogli et al. , we detei et al. . In our c et al. , who stua et al. determina et al. found thr et al. describen et al. showed tc et al. reportedc et al. , for exai et al. investigR. gallica and R. subcanina . The supernatant was filtered into a labeled vial through a syringe filter . Until further analysis, the samples were stored in a freezer at \u221220 \u00b0C. The extraction was performed in triplicate. We used a UV detector set to 210 nm for separating organic acids, a Rezex ROA column heated to 65 \u00b0C, and a mobile phase containing 4 mM sulfuric acid at a flow rate of 0.6 mL/min. Sugars were also separated at 65 \u00b0C on a Rezex RCM monosaccharide Ca + (2%) column (300 mm \u00d7 7.8 mm). The flow rate was 0.6 mL/min continuously, 30 min total run time, and bidistilled water as the mobile phase. Carbohydrates were detected using a refractive index (RI) detector.The extraction of organic acids and sugars was performed and analyzed according to the method described by Mikulic-Petkovsek et al. . Frozen g for 5 min at 4 \u00b0C . Samples were then filtered into vials through a Cromafil A-20/25 cellulose mixed ester filter . The vials containing the extracts were stored at \u221220 \u00b0C until further analysis. Samples were analyzed using an HPLC system and a UV detector set to 245 nm. The chromatographic conditions for determining ascorbic acid were previously described by Mikulic-Petkovsek et al. [Ascorbic acid extraction was performed on rosehips, pulp with skin (without seeds), as described by Kunc et al. . Fifteenk et al. . A Rezexv/v/v) and the second solvent B: acetone/ethyl acetate . The flow rate was 1 mL/min with the following gradient: from 10 to 70% B in the first 18 min, then linearly at 70% B up to 22 min and back to the initial conditions until the end of the run.Carotenoids were extracted according to the method described by Mikulic-Petkovsek et al. . Brieflyg for 7 min at 4 \u00b0C with an Eppen-Dorf 5810 R centrifuge. The supernatant was filtered through a 0.20 mm polyamide/nylon filter . Vials with extracts were stored at \u221220 \u00b0C until further analysis of phenolic compounds.Phenolic compounds were studied from the petals of the investigated genotypes. Extractions were performed according to the extraction method previously described by Kunc et al. . All anaAnalysis of phenolic constituents was performed using the Thermo Scientific Dionex HPLC system with a diode detector connected to Chromeleon workstation (software Launch Chromeleon 7). The chromatographic method for phenol analysis was previously described by Mikulic-Petkovsek et al. . The detPhenolic compounds were identified using electrospray ionization (ESI) mass spectrometer . It works in positive (anthocyanins) or negative ionization mode. All mass spectrometer conditions were identical to those described by Mikulic-Petkovsek et al. . SpectraFor statistical data processing, data were collected using Microsoft Excel 2016 and R Commander (R i386 4.1.2) using one-way analysis of variance (ANOVA) with species as a factor. Duncan\u2019s test was used to compare treatments when ANOVA showed significant differences between values. Results were expressed as mean \u00b1 standard error (SE). When p-values were less than 0.05, differences between genotypes were statistically significant. Principal component analysis (PCA) was performed for all rosehip data (pulp with skin). We also checked the correlation of each metabolite with the Pearson correlation with the corresponding matrix.We found a strong positive correlation between the total content of phenolic compounds and ascorbic acid, the total content of organic acids and the total content of carotenoids, and the total content of sugars and organic acids. The studied rosehips had an extremely low sugar content and, consequently, an extremely high organic acid content. The carotenoid content of the rosehips was in the lower range of the average content previously reported in the literature. However, since the carotenoid content depends, among other things, on the harvesting time, it would be necessary to study different harvesting dates in more detail to check whether the carotenoid content is higher on a specific date. Rose hips with higher carotenoid content, by optimizing the harvesting time, could potentially be used for industrial purposes. In addition, how the content of \u1e9e-carotene in rosehips changes, which is necessary for the formation of vitamin A, would also be interesting to analyze in the future. However, we found that the analyzed flowers are a rich source of phenolic compounds that benefit humans and could potentially be used in the food and cosmetic industries."} +{"text": "Alzheimer\u2019s disease is the most common form of dementia, affecting millions of people worldwide. Despite intensive work by many researchers, the mechanisms underlying Alzheimer\u2019s disease development have not yet been elucidated. Recently, more studies have been directed to the investigation of the processes leading to the formation of neurofibrillary tangles consisting of hyperphosphorylated microtubule-associated Tau proteins. Pathological aggregation of this protein leads to the development of neurodegeneration associated with impaired neurogenesis and apoptosis. In the present study, the effects of central administration of aggregating human Tau protein on the expression of the Bdnf, Ntrk2, Ngfr, Mapt, Bax and Bcl-2 genes in the brain of C57Bl/6J mice were explored. It was found that five days after administration of the protein into the fourth lateral ventricle, significant changes occurred in the expression of the genes involved in apoptosis and neurogenesis regulation, e. g., a notable decrease in the mRNA level of the gene encoding the most important neurotrophic factor BDNF (brain-derived neurotrophic factor) was observed in the frontal cortex which could play an important role in neurodegeneration caused by pathological Tau protein aggregation. Central administration of the Tau protein did not affect the expression of the Ntrk2, Ngfr, Mapt, Bax and Bcl-2 genes in the frontal cortex and hippocampus. Concurrently, a significant decrease in the expression of the Mapt gene encoding endogenous mouse Tau protein was found in the cerebellum. However, no changes in the level or phosphorylation of the endogenous Tau protein were observed. Thus, central administration of aggregating human Tau protein decreases the expression of the Bdnf gene in the frontal cortex and the Mapt gene encoding endogenous mouse Tau protein in the cerebellum of C57Bl/6J mice. Alzheimer\u2019s disease (AD) is the most common cause of dementiawith a prevalence of 24 million and an incidence ofup to 5 million cases per year . Russia isamong the nine countries with the highest number of peoplesuffering from AD .The annual death rate from AD and other forms of dementia inRussia in 2016 reached 35.7 per 100,000 inhabitants , however, since many cases of AD remain unreported,this number is likely to be greatly underestimatedAD is characterized by two main histopathological features:(1) extracellular amyloid plaques formed by insoluble aggregatesof hydrophobic beta-amyloid peptides and (2) intracellularneurofibrillary tangles composed of hyperphosphorylatedmicrotubule-associated Tau proteins. The accumulationof these two major types of aggregates leads to irreversibleneurodegeneration that slowly spreads throughout the brainand causes progressive memory loss, cognitive decline, severedementia and, finally, death . Althoughmany generations of researchers have tried to unravelthe mechanisms underlying this disease, they are still far frombeing fully understood. In recent years, the attention of anincreasing number of scientists has been directed to studyingthe mechanisms leading to Tau pathology developmentTau protein is a member of the microtubule-associated protein(MAP) family. Physiologically, this protein is involved inthe formation and stabilization of microtubules in neurons andin the regulation of axonal transport and axon growth . The protein\u2019s main function is the regulation oftubulin polymerization, but it has also been shown to haveDNA/RNA protection and signaling functions as well as toplay a role in transcription regulation . Under pathological conditions,the accumulation of the protein\u2019s insoluble aggregatesleads to the development of neurodegeneration, which isobviously leads to deteriorated neurogenesis and apoptosis,e. g., it has been shown that the level of Tau protein expressionnegatively correlates with the expression of BDNF playing an important role in neuron developmentand support . A similar correlation has been demonstrated for pathologicalTau protein hyperphosphorylation .Increased Tau protein expression also leads to a decrease in theBDNF level of blood plasma . Variousactions that increase BDNF expression suppress the expressionand pathological hyperphosphorylation of Tau protein . Medications, including those ofplant origin, that improve the performance of cognitive tasksin various models, reduce the expression of Tau protein andthe proapoptotic BAX protein gene, which is accompaniedby an increase in the expression of the antiapoptotic BCL- 2protein , an increase in BDNF expression, as well as an increasein the expression and phosphorylation of the TrkB receptorsmediating the positive effects of BDNF . TrkB receptor activation has led to a decreasein Tau protein phosphorylation both in vitro, in cell culture,and in animal models .The association between the nonspecific p75 receptormediatingthe proapoptotic effects of the BDNF precursor and Tau pathology isless clear. Some studies have demonstrated that the adverseeffects of agingand inflammation may be mediated at leastpartially by increased expression of the p75 receptor . At the same time, p75 receptor blockade suppressesproNGF (nerve growth factor precursor)-induced Tau proteinphosphorylation . LM11A-31, a p75 re-ceptorantagonist, also suppresses hyperphosphorylation andpathological aggregation of Tau protein in a mouse AD model.However, it remains unclear what effect exerts introductionof aggregating human Tau proteins on the expression patternsof the genes involved in the processes of neurogenesis andapoptosis in the mouse brain. The aim of this study was toinvestigate the possibility of using standard C57Bl/6J miceafter administration of aggregating human Tau protein into theleft lateral ventricle as a model for studying Tau pathologymechanisms. In particular, we planned to evaluate the effectsof the Tau protein administration on the expression patternsof the Bdnf, Ntrk2 (encodes the TrkB receptor), Ngfr (encodesthe p75 receptor), Mapt (encodes endogenous Tau), Bax, andBcl-2 genes in the mouse brain as well as on the level andphosphorylation of endogenous mouse Tau protein.Experimental animals. The investigation was carried outon C57Bl/6J inbred male mice of 10\u201312 weeks old weighing27 \u00b1 0.3 g at Center for Genetic Resources of Laboratory Animalsof the Institute of Cytology and Genetics, Siberian Branchof the Russian Academy of Sciences (RFMEFI62119X0023).In all experimental series, the animals were kept under thestandard conditions of the vivarium that included artificial14-hour lighting, 60 % humidity, temperature of 23 \u00b0C anda free access to balanced food and water. All the proceduresinvolving experimental animals were performed in accordancewith the international rules for the treatment of animals (Directive 2010/63/EU) and Order of the Ministry of Healthof the Russian Federation on Approval of the Rules of GoodLaboratory Practice of 04/01/2016 No. 199n (registered on08/15/2016 No. 43232).Intraventricular administration of Tau protein. The humanTau protein was synthesized at Convergence ResearchCenter for Diagnosis, Treatment and Care System of Dementia,Brain Science Institute, Korea Institute of Science andTechnology (KIST) and kindly provided by the Director ofthe Institute, Dr. Yun Kyung Kim.The protein was diluted in DMSO to a concentration of2 mg/ml and then diluted with saline to a concentration of0.2 \u03bcg/\u03bcl to be microinjected into the left lateral ventricle ofthe mice\u2019s brain (i.c.v.), AP: \u20130.5, L: \u20131.6 mm, DV: 2 mm under stereotaxic control . Before the injection, the mice had been narcotizedfor 20\u201330 sec with diethyl ether .Mice in the control group received an injection of the solventof the same composition. The volume of centrally injectedfluids was 5 \u03bcl. Three days after the injection, the animalswere placed in individual cages to remove group effects. After46\u201348 hours, the mice were decapitated, their frontal cortex,hippocampus and cerebellum (as a control brain structure thatis less involved in the implementation of the hyperphosphorylationand aggregation effects of Tau protein on cognition)were frozen in liquid nitrogen and stored at \u201380 \u00b0C prior totalRNA isolation and western blotting.RT-PCR. Total RNA was isolated using the TRIzol reagent and 1 \u03bcg of mRNA was used forsynthesizing cDNA with random hexanucleotide primer. PCRwas performed as in our previous studies . Real-time quantitativePCR was performed using the primers described in the Table.Gene expression was presented as the number of cDNA copiesrelative to 100 copies of Polr2a cDNA .Western blotting. The analysis was performed in the way ithad been done in our previous works . In brief, the total protein fraction wasisolated from brain samples. The samples were then separatedby 10 % SDS-PAGE and transferred to a nitrocellulose membrane.The membrane was then blocked with 5 % skimmedmilk powder or 5 % BSA (for Phospho-Tau Thr18) for 1 hourand then incubated with primary antibodies to Tau proteins and GAPDH in 5 % milk powder withTBS-T or in 5 % FBS with TBS-T for Phospho-Tau Thr181 for 16 hoursat 4 \u00b0C. For protein detection, the membranes were incubatedwith horseradish peroxidase conjugated with secondary antibodies in 5 % FBS with TBS-T for 1 hour at roomtemperature. Protein bands were visualized in a C-DiGit chemiluminescentblot scanner using the ClarityWestern ECL substrate . The bands werequantified using the Image Studio software .Target protein levels were normalized to that of GAPDHexpression, which is constitutive of brain cells, and presentedas a percentage of control animals. The number of analyzedsamples was n \u2265 8.Statistical analysis. The results were presented asm \u00b1 SEM, where m is the mean and SEM is the standarderror of the mean. The samples were compared using a onewayANOVA. The differences were considered significant atp < 0.05. The normality of the variances was tested using theKolmogorov\u2013Smirnov and Shapiro\u2013Wilk tests. Dixon\u2019s testwas applied to identify and exclude extreme deviations fromthe analysis.Central administration of the human Tau protein resulted ina change in Bdnf gene expression. A significant decrease inthe expression of this gene was found in the frontal cortexof the mice of the experimental group .At the same time, no changes were found in the expressionof genes encoding BDNF receptors . Also, the Tauprotein had no effect on the expression of the genes encodingproapoptotic factor BAX and antiapoptotic factorBCL-2 . Tau protein administrationdid not lead to significant changes in the expressionof endogenous Tau protein both at the mRNA and protein levels . The phosphorylationof endogenous Tau protein also did not change.In hippocampus, Tau protein administration did not causeany significant changes in the expression pattern of thestudied genes .Also, no significant changes were found in the expressionof the endogenous Tau protein both at the mRNA and protein levels . Thephosphorylation of endogenous Tau protein did not change as well .In the cerebellum, the human Tau protein also did not affectthe expression of Bdnf , Ntrk2 , Ngfr, and Bax genes. At the same time, a trend towards a decreasein the anti-apoptotic Bcl-2 gene was found . Interestingly, Tau protein administrationhad a significant effect on the expression of the gene encodingendogenous Tau protein in the cerebellum . However, no significant changes werefound in the level of endogenous Tau protein as well as in the level of its phosphorylation .AD is one of the most common causes of dementia that affectsmillions of people. It also leads to a large burden for the healthand care systems. Despite intensive research worldwide, ADmechanisms remain unclear and only symptomatic treatmentis available to dateAD is characterized by the formation of two types of proteinaggregates leading to the development of neurodegeneration.These are accumulations of extracellular amyloid plaques andintracellular neurofibrillary tangles, consisting of hyperphosphorylatedmicrotubule-associated Tau proteins. Since longtermstudies of the amyloid pathology have not brought thedesired results, in recent years more and more research groupshave directed their attention to investigating the mechanismsunderlying the Tau pathology.In this study, we investigated how central administration ofhuman Tau protein in mice affects the expression patterns ofthe genes involved in the processes of neurogenesis and apoptosis, as well as the level and phosphorylation of endogenousTau protein. It was shown that Tau protein administrationinto the lateral ventricle led to a significant decrease in theexpression of the gene encoding BDNF in the frontal cortex.Considering the critical role of this factor in neurons developmentand support , it can be assumed that a decrease in Bdnfgene expression can lead to the development of neurodegeneration.Here, it has to be emphasized that the most pronouncedneurodegenerative changes, as well as cell function changesin AD, have been observed precisely in the frontal cortex andhippocampus . This isdue, among other things, to the enhanced accumulation ofTau protein aggregates in these brain structures and the role of these brain structures in cognitivefunction regulationIt is noteworthy that Tau protein administration also hadits effect on the cerebellum that is not that much involved incognitive processes. Our study demonstrated that the expressionof the Mapt gene encoding the endogenous Tau proteinwas reduced in the cerebellum of the mice of the experimentalgroup. In part, these results are consistent with the data onaccumulation of Tau protein aggregates in this brain structure. However, the detected changes in theTau protein mRNA level in the cerebellum did not lead tosignificant changes in the level of endogenous Tau proteinand its phosphorylation. Also, no changes were observed inthe levels of mRNA, protein, and phosphorylation of the endogenousTau protein in all structures studied. The centraladministration of Tau protein did not significantly affect theexpression of other studied genes.In general, our data agree with those on a negative correlationbetween Tau protein expression and hyperphosphorylation with BDNF expression.However, despite the well-documented relationship betweenTau protein expression and that of pro- and anti-apoptoticgenes ,as well as the gene encoding the TrkB receptor , the administration of Tau protein did notaffect the expression patterns of these genes. An assumptioncan be made that the exogenous Tau protein introduced intothe intercellular space penetrates poorly inside the neuronsor is quickly catabolized there, not having the time to initiatea process of cells degeneration. Probably, for a more thoroughinvestigation of the effects of Tau protein aggregation on thebrain function, it is necessary to ensure endogenous expressionof the pathologically phosphorylated Tau proteins in neuronsThe results obtained in this study indicate that central administrationof human Tau protein to C57Bl/6J mice has a veryweak effect on the expression of the investigated genes involvedin neurogenesis and apoptosis. Nevertheless, Tau proteinadministrationhas led to a decrease in the expression ofBdnf gene in the frontal cortex and endogenous Tau proteinencodinggene in the cerebellum of C57Bl/6J mice withoutaffecting the level and phosphorylation of endogenous Tauprotein in the studied brain structures.The authors declare no conflict of interest.Alvarez X.A., Winston C.N., Barlow J.W., Sarsoza F.M., Alvarez I.,Aleixandre M., Linares C., Garcia-Fantini M., Kastberger B., WinterS., Rissman R.A. 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Cap\u2010independent translation of GPLD1 enhances markers of brain health in long\u2010lived mutant mice. In the original published version of the above article, the authors\u2019 would like to expand the acknowledgement section. The corrected Acknowledgments are provided below:"} +{"text": "In the original publication , there w1,\u2020, Piergiorgio Capaci 1,\u2020, Fabrizio Barozzi 1,\u2020, Danilo Migoni 1, Makarena Rojas 1, Egidio Stigliano 2, Francesco Paolo Fanizzi 1, Gian Pietro Di Sansebastiano 1,*, Paride Papadia 1,*.Chiara Anglana A correction has been made to the Author Contributions (Page 11):Author Contributions: C.A., P.C., F.B., P.P. and G.P.D.S.: equally contributed to the study design and implementation. Material preparation and data collection were performed by C.A., P.C., F.B., M.R. and F.P.F. provided the reagents and the facilities used for all the chemical analysis. Chemical analysis were performed by F.B. and D.M. The first draft of the manuscript was written by P.P. and G.P.D.S. The manuscript was critically reviewed by F.P.F., C.A., P.C., F.B., and E.S. All authors have read and agreed to the published version of the manuscript.The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Staphylococcus species was relatively high, and only coagulase-negative staphylococci (CoNS) were isolated. In sheep, S. vitulinus was the most common species, followed by S. equorum , S. lentus , S. sciuri , S. xylosus , S. warneri , S. simulans , and S. nepalensis . In the goats, the most common species was S. sciuri, which was detected in 13 (29.5%) animals. The goat skin was also inhabited by S. equorum , S. vitulinus , S. cohnii , S. lentus , S. suscinus , S. caprae, , S. auricularis , S. warneri , and S. xylosus . Only one S. xylosus strain of goat origin carried the enterotoxin gene (sea). Antimicrobial resistance was not common among the isolated staphylococci. Only 31 (37.3%) strains were resistant to at least one antimicrobial agent, with the highest frequency of resistance to penicillin (16.8%), followed by clindamycin (9.6%), erythromycin (8.4%), moxifloxacin (8.4%), and tetracycline (7.2%). All isolates were susceptible to eight antibiotics , representing six different classes. Three isolates displayed a multi-resistance phenotype (MDR): the goat isolates S. cohnii and S. sciuri, as well as the ewe isolate S. xylosus. The MDR S. cohnii isolate was found to be methicillin-resistant and carried the mecA gene. Moreover, the staphylococci isolated from the healthy animals carried genes conferring resistance to \u03b2-lactams , tetracyclines , macrolides , lincosamides (lnu), and fluoroquinolones (grlA). However, the prevalence of these genes was low.Staphylococci colonize the skin and mucous membranes of different animals. The purpose of this study was to determine the staphylococcal composition of the skin microbiota of healthy, non-vet visiting, and antimicrobially non-treated sheep and goats. In total, 83 strains (44 from goats and 39 from sheep) were isolated and identified using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The diversity of the isolated Staphylococcus epidermidis is the most abundant species on human skin. The coagulase-positive staphylococci (CoPS) S. intermedius and S. pseudintermedius are the most prevalent bacteria in the skin microbiota of domestic animals (dogs and cats), whereas S. lentus is the most common species in healthy pigeons [Staphylococcus strains associated with skin infections [S. aureus, although other bacteria, e.g., S. hyicus, S. haemolyticus, S. warneri, S. epidermidis, S. chromogenes, S. caprae, S. simulans, and S. xylosus, have also been isolated from some cases of disease [S. aureus and other coagulase-positive staphylococcal species: S. hyicus, S. intermedius, and S. schleiferi are associated with clinical mastitis in ewes [S. epidermidis, S. saprophyticus, S. simulans, S. xylosus, S. warneri, and S. chromogenes, have been isolated from cases of clinical mastitis [Staphylococci are commonly found on the skin of humans, other mammals, and birds. There are differences in the composition of staphylococci in the skin microbiota between animals and humans. The coagulase-negative staphylococci (CoNS) pigeons ,2,3. Litfections . Follicufections . Staphylfections . In shee disease . Further in ewes . Also, cmastitis , enabling horizontal transmission between isolates. Notably, methicillin-resistant staphylococci (MRS) are often multi-drug-resistant , which extremely limits therapeutic options [Recent studies have reported increased resistance to \u03b2-lactams, tetracyclines, clindamycin, and less frequently, fluoroquinolones. The major threat to human and animal health associated with staphylococci is their methicillin resistance. Methicillin resistance associated with carriage of the options ,11. Rece options . This as options .Staphylococcus sp. (MRS).This study was focused on commensal staphylococci in the skin microbiota of healthy sheep and goats. Moreover, another aim was to determine whether the animal skin was colonized by methicillin-resistant Staphylococcus species was relatively high. In total, 18 different species, all belonging to the CNS, were identified. In sheep, S. vitulinus was the most common species, followed by S. equorum , S. lentus , S. sciuri , S. xylosus , S. warneri , S. simulans , and S. nepalensis . In the goats, the most common was S. sciuri, which was detected in 13 (29.5%) animals. The goat skin was also inhabited by S. equorum , S. vitulinus , S. cohnii , S. lentus , S. suscinus , S. caprae, , S. auricularis , S. warneri , and S. xylosus .blaZ gene. Only one strain (S. cohnii isolated from the goats) presented a methicillin resistance phenotype. The strain was resistant to cefoxitin in the disk diffusion method and the harbored mecA gene. Three strains were multidrug resistant (MDR): S. cohnii was resistant to cefoxitin, penicillin, tetracycline, and tobramycin; S. sciuri was resistant to moxifloxacin, erythromycin, and clindamycin; and S. xylosus was resistant to penicillin, erythromycin, and clindamycin. The profiles of antimicrobial resistance and resistance genes detected in each strain are presented in S. equorum strain with the ermB gene detected) and clindamycin (2 S. sciuri strains with the lnu gene detected).Overall, 37.3% of the isolated strains were resistant to at least one antibiotic. The highest resistance rate was detected for penicillin (16.8%), clindamycin (9.6%), erythromycin (8.4%), moxifloxacin (8.4%), and tetracycline (7.2%) . The detStaphylococcus strains tested negative for enterotoxin-coding genes except for one S. xylosus strain isolated from sheep where the sea gene was detected.All the Staphylococcus species isolated from the skin microbiota of these animals was relatively high. Ten different staphylococcal species were detected in the goats, while eight species were identified in the sheep. A previous study reported only two species, i.e., S. aureus and S. epidermidis, isolated from the body sides of healthy sheep and goats [S. lentus, S. aureus, S. epidermidis, S. xylosus, and S. caprae were isolated from the nasal cavity, vagina, udder, and anus of dairy goats. However, these animals suffered from mastitis. The most prevalent species was S. lentus [S. sciuri was the dominant bacterial skin colonizer of goats, whereas S. vitulinus was the most frequently isolated from the ewe skin microbiota. Of note, the phylogenomic analyses of the Staphylococcaceae family suggest the taxonomic reassignment of five Staphylococcus species, i.e., S. sciuri, S. fleurettii, S. lentus, S. stepanovicii, and S. vitulinus, to the novel genus Mammaliicoccus, with Mammaliicoccus sciuri as the type species [S. sciuri, S. vitulinus, and S. lentus were common species of the animal skin microbiota. Additionally, S. equorum were isolated frequently from the ewe and goat skin. We observed differences in the staphylococcal composition between sheep and goat. S. cohnii, S. suscinus, S. caprae and S. auricularis were present only on the goat skin. In contrast, S. simulans and S. nepalensis were found only in the ewe\u2019s skin. Noteworthy, the healthy skin was not colonized by CPS. It is well known that S. aureus and other CPS, particularly S. schleiferi and S. pseudintermedius, as well as coagulase-variable S. hyicus, are important veterinary pathogens responsible for infections in a number of different animal species [S. aureus was documented among sheep and goats treated at the University of Veterinary Medicine in Austria [S. aureus in their nares [This is the first study incorporating MALDI-TOF-MS to successfully characterize commensal staphylococcal populations in healthy sheep and goats. It should be emphasized that these were no-vet visiting and antimicrobially non-treated animals. We isolated 83 staphylococci and were able to assign all the isolates to 18 different species. The diversity of the nd goats . In anot. lentus . In this species . As ment species . Nasal c Austria . Also, asea) in staphylococci colonizing non-hospitalized animals. We found the enterotoxin gene only in one S xylosus strain, isolated from the goats. In a previous study, no enterotoxin genes were detected in any CNS strains isolated from goats with mastitis; however, sec and see were identified in S. aureus [see gene was found in a single S. lentus strain isolated from goats\u2019 milk [S. aureus strains recovered from clinical mastitis and subclinical mastitis cases in goats, sheep, and bovines.Another focus of this study was the identification of enterotoxin genes , representing six different classes. Overall, we found that 41% of the isolates were susceptible to all the tested antimicrobials, and only 3.6% of the isolates exhibited multi-resistance. Among all the isolates, 26 (37.34%) were found to be resistant to at least one antimicrobial agent, with the highest frequency of resistance to penicillin, followed by clindamycin, erythromycin, moxifloxacin, and tetracycline. A single n Greece , but thery goats . These sdic acid .tek(K) gene encoding membrane-associated efflux proteins conferring resistance to tetracycline was detected in two S. lentus strains. The tetL gene was present in a single S. cohnii isolate from the goats. Moreover, the erm (B) and erm (C) genes, which code for methylases that modify the target site in 23S rRNA and inhibit the binding of macrolides, lincosamides, and streptogramin B MLSB to the bacterial ribosome, were present in the goat S. equorum and S. sciuri isolates. The presence of the ermC gene in a S. sciuri isolate from sheep has previously been reported [mphC-coding macrolide phosphotransferase was found in a S. lentus isolate of ewers origin [lnu(A) encoding a lincosamide nucleotidyltransferase was detected in two S. lentus isolates from goats. Only one S. vitulinus isolate carried grlA, which codes for resistance to phenicols. The blaZ gene encoded \u03b2-lactamases were identified in three strains of goat\u2019s origin, i.e., S. cohnii, S. sciuri, and S. warneri and in ten strains of ewe\u2019s origin, i.e., S. equorum, S. lentus, S. sciuri, S. vitulinus, and S. xylosus. Gharsa et al. [blaZ as well as tet(K) genes in Staphylococcus aureus isolated from nasal swabs of healthy sheep. Importantly, methicillin resistance conferred by the gene mec A was found in one S. cohnii isolate colonizing the goats. A study focused on S. aureus reported the presence of the mecA gene in five strains isolated from healthy sheep [mecA gene in 12 strains isolated from hospitalized goats [S. aureus and two methicillin-resistant S. epidermidis strains.Screening for genes encoding resistance to many classes of antimicrobial agents, such as penicillin, cephalosporins, tetracyclines, macrolides, lincosamides, and aminoglycosides, indicated their presence in only 11 staphylococcal strains. Among sheep isolates, reported . In anota et al. reporteded goats . More reTo summarize, resistance to tetracyclines and penicillin was found among the staphylococci isolated from healthy sheep and goats. It is important because these antibiotics are used as first-line treatments in veterinary medicine. However, no resistance to trimethoprim-sulfamethoxazole, which is commonly used in veterinary practice, was detected. Also, all staphylococci strains were susceptible to gentamycin, amikacin, and ciprofloxacin, i.e., antibiotics that are clinically effective in veterinary medicine. Moreover, the majority of stains were susceptible to erythromycin, which is used to treat staphylococcal infections in animals.In the One Health concept, the health of humans is closely connected to the health of animals. In addition to direct contact between animals and humans, antimicrobial-resistant bacteria and resistance genes may be transmitted via the food chain. The probability of transferring staphylococci to milk is high. Moreover, farm animals can be a source of microorganisms moving into their environment, which may lead to significant changes in the farm dust microbiome. The present study indicated that non-vet visiting goats and sheep from small farms are colonized by antibiotic-resistant staphylococci, including multidrug-resistant strains. However, the prevalence of antibiotic resistance genes among these strains was low. This study showed that healthy sheep and goats are colonized by a variety of CoNS staphylococci.\u00ae, Bruker, Billerica, MA, USA).Samples were collected from animals bred on small farms by private owners. The animals were not exposed to antimicrobial treatment prior to this study. Swabs were taken from the skin in the perianal area using Amies transport medium swabs . One swab was collected from each animal. The samples were inoculated on Chapman Agar . After 24 h of incubation at 37 \u00b0C, bacterial colonies with proper morphological features were isolated on Columbia Agar and then cultivated according to standard microbiological procedures. Staphylococcal strains were identified to the species level using MALDI TOF-MS (Matrix-assisted laser desorption/ionization\u2013time of flight mass spectrometry) following the manufacturer\u2019s procedure in the research mode guidelines, with the exception of amikacin, tobramycin, and tigecycline, which followed EUCAST guidelines. The following antimicrobial agents were tested: cefoxitin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, chloramphenicol, erythromycin, gentamicin, penicillin, rifampicin, tetracycline, trimethoprim/sulfamethoxazole, amikacin, tobramycin, and tigecycline.Staphylococcus strains was isolated and purified using the Genomic Mini DNA kit . The presence of se genes and antibiotic resistance genes blaZ, mecA, tetK, tetM, tetL, tetO, aac(6\u055b)/aph(2\u055b\u055b), aph(30)-IIIa, ant(40)-Ia, erm(A), erm(B), erm(C), msr(A), lun(A), gyrA, gyrB, and grlA was assessed using PCR assays as described previously [DNA from eviously ,27,28,29"} +{"text": "Reynoutriajaponica) is native to East Asia, but has been introduced to the West where it is a noxious invasive weed. Taxonomically, Japanese knotweed is placed within subtribe Reynoutriinae (Polygonaceae), which also contains the austral genus Muehlenbeckia and north temperate Fallopia. In the current study, we conducted a phylogenetic analysis using sequence data from six markers, two nuclear and four plastid to further resolve the evolutionary relationships within this group, using the widest sampling of in-group taxa to date. The results of this analysis confirmed that subtribe Reynoutriinae is a monophyletic group, characterised by the presence of extra-floral, nectariferous glands at the base of leaf petioles. Within the subtribe, four main clades were identified: Reynoutria, Fallopiasect.Parogonum, Fallopia s.s. and Muehlenbeckia. The Fallopia s.s. and Muehlenbeckia clades are sister to one another, while the Fallopiasect.Parogonum clade is immediately basal to them and Reynoutria basal to all three. Fallopia, as currently circumscribed, is paraphyletic as Muehlenbeckia is nested within it. To resolve this, we propose that species of Fallopiasect.Parogonum should be treated as a new genus, Parogonum Desjardins & J.P.Bailey, gen. et stat. nov. Within Reynoutria, the allied specific and infraspecific taxa that fall under the name Japanese knotweed s.l. form a monophyletic group and their taxonomic status is discussed.Japanese knotweed ( Reynout) Nakai) . Introdu) Nakai) . This isted taxa .Polygonaceae, Japanese knotweed s.l. is placed in subtribe Reynoutriinae (Tiniaria-type pollen (Reynoutria), the subtribe contains the austral genus Muehlenbeckia Meisn. L.H.Bailey) and the north-temperate genus Fallopia Adans.; all of which are segregates of Polygonum L. s.l. Rchb., by Reynoutria, by Fallopia and by Reynoutriinae. Muehlenbeckia, however, has traditionally been considered distinct from Fallopia and Reynoutria, primarily on the basis of its succulent mature perianth and southern biogeographical distribution. Muehlenbeckia from Polygonum s.l. and the rest of the tribe Polygoneae and placing it in tribe Coccolobeae alongside Coccoloba P.Browne, which also has inflated tepals in fruit. This classification persisted until relatively recently, being adopted as late as Muehlenbeckia may be derived from Polygonumsect.Pleuropterus (Turcz.) Benth. & Hook.f. (= Reynoutria), due to similarities in secondary chemistry and endosperm morphology. Furthermore, Fallopia and Reynoutria was probably with Muehlenbeckia, amongst other genera, as a number of morphological traits, such as fimbriate stigmas and twining habit, are found within both groups. To indicate this relationship, she transferred Fallopia and Reynoutria into the Coccolobeae to be alongside Muehlenbeckia. A summary of the historical treatments of Fallopia, Reynoutria and Muehlenbeckia is presented in Table Reynoutria, Muehlenbeckia and Fallopia in a strongly supported monophyletic group, known as the RMF clade PolygonumsectPleuropterus, containing both the erect, strongly rhizomatous knotweeds , as well as weakly rhizomatous climbers (R.multiflora (Thunb.) Moldenke and R.ciliinervis (Nakai) Moldenke). Within Reynoutria s.l., the erect, strongly rhizomatous knotweeds form an in-group, with R.multiflora as a basal lineage and have been taken to support amalgamation Ronse Decr., while R.multiflora is grouped with other perennial climbers Holub) in Fallopiasect.Sarmentosae (I.Grin\u021b.) Holub. However, the latest phylogenetic schemes have shown that Fallopia sensu Muehlenbeckia are nested within it and the dwarf, montane form var.compacta (= R.compacta), as well as East Asian endemics, such as var.uzenensis Honda (= R.uzenensis (Honda) Honda), var.terminalis (Honda) Kitag., R.elliptica (Koidz.) Migo ex Nakai and R.forbesii (Hance) T.Yamaz .Fallopia is a heterogeneous genus divided into three sections: sect. Fallopia, sect. Sarmentosae and sect. Parogonum Haraldson \u00c1.L\u00f6ve, F.cristata (Engelm. & A.Gray) Holub, F.dentatoalata (F.Schmidt) Holub, F.dumetorum (L.) Holub, F.filipes (H.Hara) Holub, F.pterocarpa Holub, F.scandens (L.) Holub (the type species) and F.schischkinii Tzvelev , spike-like to racemose inflorescences, capitate stigmas and perfect flowers Holub and F.baldschuanica, which may be conspecific with dry winged mature perianths, paniculate inflorescences, capitate stigmas, and perfect flowers Holub (the type species) and F.cynanchoides (Hemsl.) Haraldson. Species of sect. Parogonum are herbaceous perennial climbers, distinguished by their unique trichome type, a stiff unicellular hair with a papillate surface (F.convolvulus), paniculate inflorescences, mildly-fimbriate stigmas and perfect flowers , but not within Fallopia s.s., while the inclusion of a nuclear dataset placed it outside of the RMF clade and weakly supported as sister to a DAP clade (subtribe Polygoninae), including: Duma T.M.Schust, Atraphaxis L. and Polygonums.s. The separation ofsect.Parogonum from Fallopia s.s. is supported by an examination of secondary chemistry, which found that the flavonoid profile of F.ciliinodis to be substantially different from the rest of Fallopia, most closely resembling the climbing Reynoutria taxa, R.multiflora and R.ciliinervis Meisn. as the type. The genus, as currently understood, contains approximately twenty-seven species, eighteen from Australia, New Zealand and the Pacific Islands and nine from Central and South America Meisn., M.ephedroides Hook.f. and M.axillaris (Hook.f.) Endl., as well as M.tuggeranong Mallinson, an Australian endemic F.Muell., M.rhyticarya F.Muell. ex Benth. and M.zippelii (Meisn.) Danser with strong support, as well as M.adpressa (Labill.) Meisn., M.gracillima Meisn., M.costata K.L.Wilson & R.O.Makinson and M.gunnii (Hook.f.) Endl. with weaker support. Clade z is a predominantly Central/South American clade, containing: M.urubambensis Brandbyge, M.volcanica (Benth.) Endl., M.tiliifolia Wedd., M.tamnifolia (Kunth) Meisn. and, somewhat surprisingly, M.australis, a native of New Zealand and Norfolk Island, whose inclusion in this clade was hypothesised to be the result of long-distance dispersal Meisn. L.H.Bailey), an evergreen shrub with phylloclades, native to New Guinea and the Solomon Islands h endemic . Clade yispersal . The phynds e.g. ,b).Reynoutria, Fallopia and Muehlenbeckia within subtribe Reynoutriinae by including the widest sampling of ingroup taxa for the clade to date, in particular being the first to include infraspecific taxa and allies of R.japonica, as well as both taxa of Fallopiasect.Parogonum. A phylogenetic analysis was conducted on sequence data from six markers: two nuclear, the second intron of LEAFY (LEAFYi2) and the internal transcribed spacer (ITS) of the 17S-5.8S-26S rDNA region; and four plastid, matK, rbcL, rps16-trnK and trnL-trnF.In the current study, we further resolved the evolutionary relationships of LTR).An accession list for the current study is presented in Suppl. material Reynoutria, nineteen Muehlenbeckia and nine Fallopia taxa were included. Published taxa that are missing from the current study include: F.filipes, F.koreana, F.pterocarpa, F.schischkinii, M.andina Brandbyge, M.fruticulosa Standl., M.hastulata (Sm.) I.M.Johnst., M.monticola Pulle, M.nummularia H.Gross, M.polybotrya Meisn., M.sagittifolia (Ortega) Meisn. and M.triloba Danser.The accessions, collected for the current study, represent the widest sampling of in-group taxa for any phylogenetic study in this subtribe to date cf. , 2015). matK, rbcL, rps16-trnK and trnL-trnF and two nuclear: ITS and LEAFYi2, were amplified by PCR. The primer sequences and cycling conditions are presented in Suppl. material LEAFYi2 was also sequenced from clones. Cloning was conducted using the pGEM-T Easy Vector System (Promega) and \u03b1-Select Competent Cells taken from E. coli (Bioline). Recombinant plasmids were selected by blue-white screening and the size of the insert determined by colony PCR with M13 primers. Plasmid DNA was isolated from cell cultures using the E.Z.N.A. Plasmid Mini Kit (Omega Bio-tek) and a minimum of five colonies were sequenced per accession.Total genomic DNA was isolated from dried leaf material using the DNeasy Plant Mini Kit (Qiagen). Six markers, four plastid: http://www.geneious.com/). The sequences were then blasted against the NCBI GenBank database to ensure taxon and gene matches. In total, 259 sequences were used, 107 (41%) of these were newly generated for the current study and 152 (59%) were downloaded from the NCBI GenBank database , LEAFYi2 and the ITS were analysed separately and then concatenated to produce a total evidence dataset. Not all gene regions were available for all taxa and some taxa had incomplete datasets and Maximum Parsimony (MP). ML analysis was conducted using PhyML 3.0 (NNI) search strategy. Maximum Parsimony (MP) analysis was conducted using PAUP* 4.0 - 1000 replicates , combined chloroplast and total evidence datasets. Congruence between trees was determined by comparison of BS values.Two methods were used to infer the evolutionary relationships of the taxa from the datasets, Maximum Likelihood (hyML 3.0 . The moshyML 3.0 and the AUP* 4.0 . Topologplicates . Two speablished . They coAll sequences generated for this study have been deposited on GenBank (NCBI). Sequence alignments are available in the Suppl. materials ML and MP. The two analyses were largely congruent, although bootstrap support (BS) values for ML were generally higher. The trees presented are displayed above and below branches for ML and MP, respectively. Hyphens (-) indicate nodes where MP trees differ from ML in branching order. BS values from ML analysis are cited in the main text, unless otherwise stated.Phylogenetic trees were generated by LEAFYi2 and combined chloroplast datasets were analysed separately produced poorly-resolved trees and branches with strong support were largely confined to termini In the combined chloroplast tree, R.japonicavar.compacta was sister to R.sachalinensis with strong support (84% BS), while in the total evidence tree, it was placed in a weakly-supported R.japonica s.l. clade (55%), to which R.sachalinensis was basal; 2) In the combined chloroplast analyses M.ephedroides fell within a clade with M.axillaris and M.tuggeranong (78% BS), while in the total evidence analysis, it was sister to M.australis (97% BS).The ITS, The results of the total evidence analysis gave greater resolution and a higher number of strongly-supported nodes than the individual nuclear and combined chloroplast trees alone. In our view, the total evidence tree is the best estimate of the phylogenetic relationships in this study; hereafter, this is the tree described (unless otherwise stated) and forms the basis of our discussions.Reynoutriinae formed a well-supported (93% BS) clade within the Polygonaceae; sister to a subtribe Polygoninae clade (100% BS). Within subtribe Reynoutriinae, there were four well-supported subclades: A) a Reynoutria clade (77% BS with R.multiflora and 99% BS without); B) a Fallopiasect.Parogonum clade (100% BS); C) a Fallopia s.s. clade (100% BS) and D) a Muehlenbeckia clade (100% BS). The Fallopia s.s. and Muehlenbeckia clades were sister to one another with the Fallopiasect.Parogonum clade immediately basal to them (100% BS) and the Reynoutria clade basal to all three (55% BS).Subtribe Reynoutria clade contained R.multiflora, R.ciliinervis, R.sachalinensis, R.japonicavar.compacta, R.elliptica, R.forbesii, R.japonicavar.terminalis, R.japonicavar.uzenensis and R.japonicavar.japonica. Within the clade, the erect Reynoutria taxa formed a strongly-supported subclade (100% BS), with R.ciliinervis (99% BS) and R.multiflora (77% BS) as independent basal lineages. However, relationships within the erect subclade were poorly resolved with only weakly-supported internal nodes. Nevertheless, there were two clear subclades within it, a strongly-supported one containing R.elliptica + R.forbesii (94% BS) and a moderately-supported one containing R.japonicavar.terminalis, R.japonicavar.japonica + R.japonicavar.uzenensis (71% BS).The Fallopiasect.Parogonum clade contained the sister taxa F.cynanchoides and F.ciliinodis with strong support (100% BS). The Fallopia s.s. clade contained two strongly-supported subclades, C1) a sect. Fallopia clade (100% BS) and C2) a sect. Sarmentosae clade (100% BS). The sect. Fallopia clade contained F.convolvulus, F.dentatoalata, F.dumetorum, F.cristata and F.scandens. All relationships within the clade there were strongly supported. Within this clade, F.cristata and F.scandens were almost identical and were placed as sister taxa (100% BS). The sect. Sarmentosae clade contained the sister taxa F.baldschuanica and F.aubertii with strong support (100% BS).The Muehlenbeckia clade contained three subclades with moderate to strong support, although the relationships between them were entirely unresolved: D1) a Central/South American clade (100% BS); D2) an Australian clade (64% BS) and D3) a predominantly New Zealand clade (86% BS). The American clade contained M.tiliifolia, M.tamnifolia, M.volcanica and M.urubambensis. All relationships within the clade were strongly supported. Within this clade, there were two pairs of sister taxa, M.tiliifolia + M.tamnifolia (99% BS) and M.volcanica + M.urubambensis (77% BS). The Australian clade contained M.gracillima, M.costata, M.gunnii, M.arnhemica, M.zippelii, M.diclina and M.rhyticarya. All relationships within the clade were moderately/strongly supported. Within this clade, there were two subclades, one containing M.gracillima, M.costata and M.gunnii (70% BS) and another containing M.zippelii, M.arnhemica, M.diclina and M.rhyticarya (74% BS). The predominantly New Zealand clade contained M.australis, M.ephedroides, M.astonii, M.complexa, M.axillaris, as well as the Australian endemic M.tuggeranong. All relationships within the clade were moderately/strongly supported. In this clade, there were two subclades, one containing M.australis + M.ephedroides (97% BS) and another containing M.astonii, M.complexa, M.axillaris + M.tuggeranong (58% BS). Within this second subclade, M.axillaris and M.tuggeranong were sister taxa with strong support (100% BS). The placement of M.platyclada and M.adpressa within the genus was unresolved.The LEAFYi2 was single-copy in all diploid taxa and was sequenced directly, but in two polyploid taxa, R.japonicavar.japonica and F.convolvulus, two amplicons of different size were observed and these were sequenced from clones , while in F.convolvulus, the two copies were separate on the tree. Copy 1 was sister to F.dumetorum (100% BS), while the position of copy 2 was unresolved in the ML analysis (< 50% BS), but placed in a clade with F.scandens and F.cristata in the MP analysis (70% BS).Reynoutriinae form a strongly-supported monophyletic clade within the Polygonaceae. This clade is characterised by the presence of extra-floral nectaries at the base of leaf petioles and a Muehlenbeckia clade. Fallopia s.s. and Muehlenbeckia are sister to one another, while Fallopiasect.Parogonum is basal to them and Reynoutria is basal to all three.The species of petioles and Tinilen type . The sublen type . Within Reynoutria taxa form a strongly-supported monophyletic clade within subtribe Reynoutriinae, which confirms the findings of previous molecular studies . Indeed, previous authors (e.g. R.multiflora & R.ciliinervis) and retain the climbers in their own genus, Pleuropterus. However, this is not supported by the current study as R.multiflora and R.ciliinervis do not form a reciprocally monophyletic subclade, but rather they form separate basal lineages within the Reynoutria clade. We, therefore, continue to treat both the climbing and erect taxa as Reynoutria s.l. are discontinuously distributed between East Asia and Eastern North America and is supported by seven further collections of M.australis from around New Zealand, which form a monophyletic group within the New Zealand clade . M.astonii within Muehlenbeckia, while, in the current analysis M.astonii was placed in the predominantly New Zealand clade with strong support. An examination of the sequence data used by EF635479) is likely a pseudogene, which inflated sequence divergence and resulted in the artificial separation of M.astonii from the rest of New Zealand Muehlenbeckia. This pseudogene was identified by its relatively low GC content (60.1% versus 65.5%) and the high number of SNPs in the conserved 5.8S region from Muehlenbeckia and Fallopia (x = 10). However, the inclusion of Fallopiasect.Parogonum (x = 11) in a clade with Muehlenbeckia and Fallopia s.s. breaks down this distinction. Furthermore, intrageneric variation in basic chromosome number is not uncommon in the Polygonaceae, for example, Persicaria, x = 10, 11, 12 The morphological characters used to separate perianth , but, as, 11, 12 ; 2) Therlen type ; 3) Hybrenbeckia , 2013.Muehlenbeckia has been treated as a distinct entity since its formation, while Fallopia and Reynoutria have often been treated as separate genera Muehlenbeckia is a well-established genus and in widespread usage amongst botanists in the Southern Hemisphere; 4) Muehlenbeckia has been conserved against previous priority challenges e genera ; 2) It wallenges ; 5) MuehReynoutriinae are better treated as multiple genera to limit nomenclatural upheaval, preserve names in widespread use and to better distinguish the clades. Fallopiasect.Parogonum has, therefore, been treated as a genus in its own right and the relevant binomial changes have been made below.On balance, we are of the opinion that, despite compelling arguments in favour of amalgamation, species of subtribe Fallopiaconvolvulus is tetraploid (2n = 40), but it is not known if it arose by autopolyploidy or allopolyploidy and F.scandens/F.cristata (2n = 20), followed by chromosomal doubling. F.convolvulus is derived from F.scandens and diversified relatively recently to become a weed of cereal crops. An allopolyploid origin of F.convolvulus is in line with this, as it would provide a mechanism for reproductive isolation and near-instantaneous speciation. Indeed, modern hybrids between F.convolvulus and F.dumetorum, F.\u00d7convolvuloides (Br\u00fcgger) Holub, are triploid and sterile Desjardins & J.P.Bailey, gen. et stat. nov., north temperate Fallopia and austral Muehlenbeckia. Within the subtribe, Reynoutria can be identified by the presence of rhizomes, Parogonum by stiff papillate hairs, Fallopia by capitate stigmas and Muehlenbeckia by succulent mature perianths.Subtribe Taxon classificationPlantaeCaryophyllalesPolygonaceae\ufeff Desjardins & J.P.Bailey, gen. etstat. nov.E31836CE-ABAA-556A-8412-68D814CB5217urn:lsid:ipni.org:names:77315139-1Fallopiasect.ParogonumSymb. Bot. Upsal. 22: 78 (1978). Basionym. Haraldson, Taxon classificationPlantaeCaryophyllalesPolygonaceae\ufeff1)(Michx.) Desjardins & J.P.Baileycomb. nov.F541B2F7-1C2D-531B-9F3E-4248EE7C6ED0urn:lsid:ipni.org:names:77315140-1Polygonumciliinodecilinode\u2019) Michx., Fl. Bor.-Amer. (Michaux) 1: 241 (1803). Basionym. (\u2018Tiniariaciliinodiscilinodis\u2019) (Michx.) Small, Fl. S.E. U.S. [Small].: 382 (1903). Bilderdykiaciliinodis (\u2018cilinodis\u2019) (Michx.) Greene, Leafl. Bot. Observ. Crit. 1: 23 (1904). Reynoutriaciliinodis (\u2018cilinodis\u2019) (Michx.) Shinners, Sida 3: 117 (1967). Fallopiaciliinodis (\u2018cilinodis\u2019) (Michx.) Holub, Folia Geobot. Phytotax. 6: 176 (1970). Homotypic synonyms. (Hemsl.) Desjardins & J.P.Baileycomb. nov.0BA1DE33-6D0E-525B-BD1D-DA4ED82539F0urn:lsid:ipni.org:names:77315141-1PolygonumcynanchoidesJ. Linn. Soc., Bot. 26: 338 (1891). Basionym. Hemsl., FallopiacynanchoidesSymb. Bot. Upsal. 22: 78 (1978). Homotypic synonym. (Hemsl.) Haraldson, Taxon classificationPlantaeCaryophyllalesPolygonaceae\ufeff3)(A.J.Li) Desjardins & J.P.Bailey, comb. etstat. nov.583A4EAB-4D58-54D6-8DE5-7D616C7DBD41urn:lsid:ipni.org:names:77315142-1Polygonumcynanchoidesvar.glabriusculumF. Xizang 1: 608 (1983). Basionym. A.J.Li, Fallopiacynanchoidesvar.glabriusculaFl. Reipubl. Popularis Sin. 25: 104 (1998). Homotypic synonym. (A.J.Li) A.J.Li,"} +{"text": "Germline-restricted chromosomes (GRCs) are present in the genomes of germline cells and absent from somatic cells. A GRC is found in all species of the songbirds (Passeri) and in none of the other bird orders studied to date. This indicates that GRC originated in the common ancestor of the songbirds. The germline-restricted chromosome is permanently absent from somatic cells of the songbird, while female germline cells usually contain two copies of GRC and male ones have one copy. In females, GRCs undergo synapsis and restricted recombination in their terminal regions during meiotic prophase. In males, it is almost always eliminated from spermatocytes. Thus, GRC is inherited almost exclusively through the maternal lineage. The germline-restricted chromosome is a necessary genomic element in the germline cells of songbirds. To date, the GRC genetic composition has been studied in four species only. Some GRC genes are actively expressed in female and male gonads, controlling the development of germline cells and synthesis of the proteins involved in the organization of meiotic chromosomes. Songbird species vary in GRC size and genetic composition. The GRC of each bird species consists of amplified and modified copies of genes from the basic genome of that species. The level of homology between GRCs of different species is relatively low, indicating a high rate of genetic evolution of this chromosome. Transmission through the maternal lineage and suppression of the recombination contribute significantly to the accelerated evolution of GRCs. One may suggest that the rapid coordinated evolution between the GRC genes and the genes of the basic genome in the songbirds might be responsible for the explosive speciation and adaptive radiation of this most species-rich and diverse infraorder of birds. In the late 19th century, A. Weismann proposed one of themost influential ideas in modern biology. He suggested afundamental distinction between somatic cells and germ linecells . According to A. Weismann,germline cells possess a complete set of hereditary material(germ plasm), while somatic cells undergo unequal divisionsduring their differentiation and specialization, which leads toa fragmentation of the germ plasm, with different daughtersomatic cells acquiring its different fragments.The former part of Weismann\u2019s hypothesis becamethe basis of modern evolutionary biology, genetics,and developmental biology. The latter part underwentsignificant modifications. Unequal division of somaticcells during early development in the vast majority ofmodern multicellular organisms does not lead to genomefragmentation (as suggested by Weismann), but rather tothe uneven distribution of its products (proteins and RNAs)among the daughter cells. This, in turn, leads to progressivedifferentiation of their gene activity and, ultimately, to theirspecialization .However, somatic cells in some species behave accordingto Weismann\u2019s hypothesis: they lose a portion of theirgenomes during the differentiation. This phenomenon waspreviously referred to as \u201cchromatin diminution\u201d. Theprevailing term now is \u201cprogrammed DNA elimination\u201d. The first example of chromatindiminution was discovered by T. Boveri in the nematodeAscaris megalocephala . During the earlystages of its development, the nuclei of certain cellsprogressively lose a portion of their chromosomal material.T. Boveri suggested that chromatin diminution is part of anormal developmental program necessary for the formationof specific tissues and organs in the worm .Programmed DNA elimination is observed in various taxaof multicellular organisms. It plays a key role in regulatinggene expression and maintaining genomic stability. Variousmolecular pathways involved in selective DNA removalduring chromatin diminution have been identified . It has been shown that the regions of thegenome that are eliminated are the homologous counterpartsof those undergoing silencing in other multicellularorganisms, such as oncogenes and other early developmentalgenes .Thus, programmed DNA elimination can be considereda radical form of silencing, a specific way to resolve theproblem of antagonistic pleiotropy between early andlate genetic programs. Apparently, this mechanism ofdevelopmental regulation through programmed DNAelimination has emerged repeatedly in evolution and hasproven to be an evolutionary dead end. Its erratic distributionacross the phylogenetic tree of multicellular animalssupports this hypothesis .Elimination in somatic cells usually affects chromosomefragments rather than entire chromosomes. Cases ofwhole chromosome elimination are less frequent . In several species of mammals andinvertebrates from different taxa, chromosome eliminationserves as a mechanism of sex determination and/or dosagecompensation of genes on heterogametic sex chromosomes.Conflict between host genomes and their genomicparasites sometimes leads to the emergence of additional chromosomes. They arecalled B-chromosomes, in contrast to A-chromosomesof the basic karyotype. B-chromosomes vary in size,morphology, and genetic content between species, amongindividuals within a species, and even among individualcells of an organism .Several studies detected a tendency for B-chromosomesto accumulate in germ cells and be lost in somatic cells.B-chromosomes may not be present in all populationsof a particular species. Species with B-chromosomes alsoexhibit erratic phylogenetic distribution . For example, B-chromosomes are present inonly 16 species from 11 rather species-rich genera outof 1130 species described in the \u201cAtlas of MammalianChromosomes\u201d . This suggeststhat B-chromosomes are typical genomic parasites thatoccasionally arise in some species, sometimes gain pyrrhicvictories and spread in populations, but ultimately eitherbecome completely eliminated from the genomes of thesespecies or go extinct along with their hosts .In some cases, however, such parasitic chromosomes mayachieve evolutionary success and become an indispensable partof the genome in germ cells of all or most species within largertaxa. Such germline-restricted chromosomes (GRCs) have beendiscovered in almost all studied species from three dipteranfamilies: fungus gnats (Sciaridae), gall midges (Cecidomyiidae),and non-biting midges (Chironomidae) , as well as in all studied species of passerine birds(Passeriformes) \u2013 the most species-rich and diverse orderof birds .A comprehensive review of current knowledge on GRCsin Diptera was provided by C.N. Hodson and L. Ross (2021).A recent review of GRCs in passerines was published by agroup of authors, including nearly all European researchersof this chromosome and the author of this article , in a special issue dedicated to non-Mendelianinheritance and meiotic drive . It paid special attention to hypotheses regarding themechanisms of GRC transmission in the germline and itselimination from somatic cells. Another review analyzingGRC in the context of genomic conflicts appeared online inSeptember 2023 .This review will address issues related to the structure,function, and evolution of this enigmatic chromosome.GRC in birds was first identified by Argentine cytogeneticistsM.I. Pigozzi and A.J. Solari in the zebra finch (Taeniopygiaguttata) . They stumbled uponit entirely by chance during a comparative study ofchromosome synapsis and recombination in bird meiosis.Among the numerous bird species they examined , the zebra finch wasthe first representative of Passeriformes. In the meiotic cellsof this species, they observed something that had not beenseen in any previously studied species.The germline cells of both male and female zebra finchescontained an additional chromosome that was not presentin bone marrow and other somatic cells. This additionalchromosome was larger than all other chromosomes.It was euchromatic in oocytes and heterochromatic inspermatocytes . Furthermore, infemale germline cells, it was usually present in two copies,whereas in males, it was present in a single copy .Another unexpected feature of this chromosome was itsabsence not only in somatic cells but also in spermatozoa.During pachytene, diplotene, and metaphase I of meiosis,the GRC was localized at the periphery of chromosomalplates. However, it was absent in metaphase II of malemeiosis. Additionally, round dense DAPI-positive bodieswere observed adjacent to some spermatocytes. Electronmicroscopy revealed that these round bodies weresurrounded by a double membrane. M.I. Pigozzi and hercolleagues hypothesized that these micronuclei containedGRCs eliminated after the first meiotic division .Subsequently, A.A. Torgasheva et al. (2019) confirmedthis hypothesis in a direct experiment. They microdissectedthese micronuclei, prepared DNA probes from them, andhybridized these probes to preparations of pachytenespermatocytes and oocytes. In all cases, they observeda strong, specific hybridization signal on the GRCs. Since the GRC was absent fromspermatozoa, M.I. Pigozzi and A.J. Solari (2005) and Y. Itohet al. (2009) suggested that it must be inherited exclusivelythrough the maternal lineage.Initially, M.I. Pigozzi and A.J. Solari (1998) classifiedthe zebra finch GRC as a B-chromosome. However, theynoted its unique characteristics. B-chromosomes usuallyvary in number in somatic cells and tend to accumulateingermline cells. The zebra finch GRC was absent in somaticcells and always present in every germline cell. From theoutset of the GRC investigation, it became clear that thischromosome was not a facultative but an obligate elementof the germline cell genome, essential for gametogenesis.The zebra finch GRC has long been considered an intriguinggenetic curiosity, the sole instance of the B-chromosomein birds. The discovery of GRC in germline cells of theBengalese finch (Lonchura striata domestica) did not alter this opinion. However, thesituation changed dramatically in 2018\u20132019, when threeindependent research groups published data indicating thepresence of GRC in the germline of many species of birds.A.A. Torgasheva et al. (2019) obtained direct evidenceof the antiquity of GRC in birds and its wide distributionamong songbirds. They conducted cytogenetic screening of15 songbird species and 8 bird species outside this suborder.They used immunolocalization of SYCP3, the major proteinof the synaptonemal complex , centromeric proteins, and MLH1, themismatch repair protein, which marks sites of homologousrecombination .A.A. Torgasheva et al. (2019) demonstrated that GRC ispresent in all pachytene cells of all investigated individualsof songbird species, including the rook (Corvus frugilegus),a representative of the Corvida infraorder, the sistergroup to the Passerida infraorder, which includes all othersongbird families . The size of GRC varies widely,with some species having macrochromosomal GRC of sizerank 1 to 3, and others having micro-GRC. No phylogeneticclustering has been observed for this trait: closely relatedspecies differ greatly in the size of their GRC .However, GRC exhibits considerable conservatism in termsof its morphology; in nearly all investigated species, GRCis an acrocentric chromosome. The exception is the piedflycatcher, whose GRC is metacentric .GRC has not been detected in any bird species outsidethe order Passeriformes, including the budgerigar (Melopsittacusundulatus), a representative of the order Psittaciformes,which is the sister group to the order Passeriformes. The list of species examined forthe presence of GRC now includes 27 songbird species withGRC and 9 bird species without GRC outside this suborder .Based on cytogenetic screening, A.A. Torgasheva et al.(2019) concluded that GRC is likely present in the germlinecell genomes of all songbirds and absent in all other birds.They suggested that GRC originated in the common ancestorof the Passeri suborder, which includes approximately5000 species. The germline cells of representatives of theTyranni suborder, consisting of approximately 1200 species,and the Acanthisitti suborder, which includes two species ofNew Zealand wrens, have not been analyzed yet. Therefore,it is still unknown whether they have GRC. If they have it,this would indicate that GRC emerged much earlier, in thecommon ancestor of all passerine birds.Independent evidence of the evolutionary antiquity of theGRC has been obtained by comparing the results of sequencingthe generative and somatic tissues of the zebra finch and subtractive transcriptomic analysis. Over a hundred GRC-specificgenes (gametologs) and their somatic paralogs (somatologs)have been identified on at least 19 A-chromosomes.The results of phylogenetic analysis enabled the categorizationof GRC-specific genes into five evolutionarystrata based on the degree of divergence from their somaticparalogs .The level of divergence between gametologs of theyoungest stratum 5 and their somatic counterparts is comparableto the level of divergence among the subspecies ofthe zebra finch. Gametologs of stratum 4 emerged duringthe divergence of the zebra finch from the long-tailed finch(Poephila acuticauda) and the diamond firetail (Stizopterabichenovii). Stratum 3 comprises gametologs that originatedfrom a common ancestor of estrildid species (Estrildidae),stratum 2 corresponds to the ancestor of the Passerida infraorder.The most ancient stratum 1 arose in the commonancestor of the suborder Passeri.Thus, both cytological and molecular genetic dataunambiguously indicate the monophyletic origin of the GRCWhat does GRC contain that makes it an obligate element ofthe germline genome of all songbirds? At the time of writingthis article, the results of genomic analysis of GRC have beenpublished for only four species of songbirds: the zebra finch, two species of nightingales: western,Luscinia megarhynchos and eastern, L. luscinia , and the Eurasian blue tit, Cyanistes caeruleus.The most extensively studied zebra finch GRC containsa set of genes crucial for the development of the reproductivesystem. Contrary to expectations, mobile elements andsatellite DNA are not more abundant in GRC compared toA-chromosomes; in fact, they are less abundant . Transcriptomic analysisrevealed the transcription of at least six GRC-specific genesin the testes and 32 genes in the ovaries. Mass spectrometryanalysis confirmed the translation of mRNA from some ofthese genes in the gonads of both sexes. Gene categoriesrelated to gonad formation in females and reproduction areoverrepresented in the list of GRC-specific genes. Orthologsof many zebra finch GRC-specific genes are predominantlyexpressed in the chicken gonads of both sexes . Both the macro-GRC of the zebra finch and themicro-GRC of the blue tit contain a functional paralog ofthe BMP15 transcription factor, which plays an importantrole in follicle maturation in the ovaries of birds and othervertebrates . In the GRC of the bluetit, J.C. Mueller et al. (2023) revealed the genes controllingthe formation of the synaptonemal complex and other genescontrolling chromosome synapsis and recombination.Some of the gametologs found in the zebra finch GRC,including the most ancient ones (bicc1 and trim71), aresubjected to purifying selection .The products of their orthologs play an important role in the differentiation of mammalian embryonic cells . The bicc1 gene encodes an RNA-bindingprotein that modulates protein translation during embryonicdevelopment. The product of the trim71 gene binds tomicroRNAs and supports the growth and proliferation ofembryonic stem cells. It is also involved in cell cycle control.The gametolog of the puf60 gene shows signs of recent positiveselection. It encodes a protein playing an important rolein multiple nuclear processes, including pre-mRNA splicingand transcriptional regulation . Thesedata clearly indicate the functional significance of at leastsome of the gametologs. However, some genes in the GRCof the blue tit and many genes in both species of nightingaleshave undergone pseudogenization and presumably lost theirfunctional significance .Interestingly, the duplication of genes from the somaticgenome into GRC did not lead to the loss of their \u201coriginal\u201dcopies. Moreover, in the blue tit, a positive correlation in the number of copies was found between gametologs and theirsomatologs .Thus, GRCs of all four investigated species contain copiesof A-chromosome genes, many of which control thedevelopment and functioning of germ cells.In almost all male pachytene cells , at least one GRC is present. Itappears as a univalent with a twisted, sometimes fragmented,single axial element of the synaptonemal complex surroundedby chromatin, intensely labeled with anticentromereantibodies. The univalent does not undergo synapsis andrecombination neither with itself nor with A-chromosomes.In almost all female pachytene cells , two GRCs are present. Theysynapse along their entire length, forming bivalents, andundergo recombination. The only difference between GRCbivalents and A-chromosome bivalents is the distribution ofthe recombination sites. There are fewer recombination citeson GRC bivalents compared to A-chromosome bivalents ofsimilar size, and they occupy more distal positions on theGRC bivalents .With an increase in the number of species and individualsstudied, and the use of molecular probes, many exceptionswere identified. Five females (one zebra finch and four sandmartins) out of 50 individuals of seven species examinedhad one GRC (instead of two) in all their pachytene cells. Four females of the great tit out ofseven examined were mosaic for the number of GRCs: oneGRC was observed in a small fraction of their cells (from 2to 26 %), while the rest contained two GRCs .Among 76 males of 26 investigated species, no individualswith more than one GRC in all germ cells have beenfound so far. However, nine males exhibited mosaicism in the number of GRCs . Some germ cells of mosaic males contained twoor even three GRCs . The maleblack-headed munia was mosaic not only in the number butalso in the size of GRCs. Some of its cells contained onemacro-GRC and one micro-GRC .Sexual dimorphism in the meiotic behavior of GRC ismaintained even in the germ cells, which contain atypicalnumbers of GRC for their respective sexes. The two axialelements of GRC in male pachytene cells show incompletesynapsis and extremely rare recombination . However, even in the case of such recombinationoccurring in male meiosis, it would not play a role inthe evolution of the genetic composition of the GRC dueto the extremely low chance of GRC transmission throughmales .The almost exclusive transmission of the GRC throughthe maternal lineage, coupled with the fact that recombina-tion in most regions of the GRC is suppressed, suggeststhat the GRC in songbirds represents a new genomic elementsubject to the action of the Meller\u2019s ratchet, in additionto the sufficiently gene-rich W chromosome and themitochondrialgenome. Non-recombining genomic elementsare characterized by an exceptionally high rate of fixationof point and structural mutations . Itcan be hypothesized that the GRC should evolve at a highrate and accelerate the evolution of the entire suborder ofsongbirds.The rate of GRC evolution can be assessed by the degree ofdivergence in the genetic composition of the GRC amongdifferent bird species. A rough estimation of the degreeof homology between GRCs of several bird species wasobtained using reciprocal fluorescent in situ hybridization(FISH). This method revealed an astonishingly low degree ofhomology between GRCs of different species, which couldindicate a rapid evolution of the genetic composition of theGRC .The initial results of the genomic analysis of GRCs fromdifferent species confirm the assumption of an exceptionallyhigh rate of GRC evolution. The GRCs of the westernnightingale (L. megarhynchos) and the common nightingale(L. luscinia), which have undergone independent evolutionfor only 1.8 million years, show considerable divergence.Among the 585 gametologs of the western nightingale andthe 406 gametologs of the common nightingale, only 192of them are shared. Among them, only 25 are shared withthe GRC of the zebra finch. In other words, only one-thirdof the identified gametologs is inherited from a commonancestor of the closely related nightingale species. For example,nearly half of the GRC of the common nightingaleconsists of a large, albeit fragmented, segment homologousto the undivided segment of A-chromosome 2. This geneticmaterial has not been identified in the western nightingaleat all .Segmental copying of A-chromosome regions into theGRC, followed by the dispersal of these regions within theGRC, is observed in all species that have been sufficientlystudied. For example, a major portion of the GRC of thezebra finch consists of dispersed sequences homologousto a segment from the short arm of chromosome 3 . The fragments fromthe long arm of the same chromosome and from one of themicrochromosomes were found to be homologous to theGRC sequences of the siskin. The GRC of the sand martincontains material from chromosomes 4 and W, while theGRC of the great tit is partly homologous to one of themicrochromosomes .The mechanisms of copying and dispersing fragmentsof A-chromosomes in the GRC remain unknown. Recombinationbetween the GRC and A-chromosomes is unlikely A.A. Torgasheva et al. and L.P. Malinovskayaet al. (2020) did not observe in females of four studiedsongbird species any ectopic contacts between GRC andA-chromosomes, which could lead to recombinationand/or conversion. They did not detect a self-synapsis ofthe GRC synaptonemal complexes, which could lead todeletions, duplications, and dispersal of sequences withinthe GRC, either.The remarkable range of inter-species variability in sizeand heterogeneity in the genetic composition of GRC indicatean extraordinary evolutionary fluidity of this remarkablechromosome. Gametologs constantly accumulate pointmutations, gradually diverging from their somatologs andgametologs of other species. At the same time, differentgametologs constantly emerge within the GRCs of differentspecies by copying from different regions of differentA-chromosomes. Some gametologs amplify in the GRC,increasing its size, while the deletion of others (or the sameones?) results in its reduction. These processes of growth andcontraction of the GRC affect different regions in differentspecies, enhancing the divergence of their GRCs.The distribution of GRC among birds and the estimates of the divergence time betweengametologs and somatologs of the zebra finch unequivocally indicate amonophyletic origin of GRC in the songbirds.A.A. Torgasheva et al. (2019) hypothesized that the firstGRC could have arisen in the genome of ancestral songbirdsthrough a trisomy of one of the microchromosomes. Theancient nature of GRC in songbirds and its extraordinarygenetic fluidity leave no hope of finding A-chromosomeparalogs, which would be the last common ancestor of GRCin all songbirds.An analysis of B-chromosomes in different speciessuggests that they are derived from fragments of A-chromosomescontaining the centromere, which arise duringchromosomal rearrangements in the germ line .Interchromosomal rearrangements are fixed in bird evolutionmuch less frequently than in other vertebrate taxa.The diploid number (2n) of the absolute majority of birdspecies varies within a very narrow limit: 80 \u00b1 2, and mostof the chromosomes in modern birds are syntenic to thereptilian chromosomes . Intrachromosomal rearrangements,particularly inversions, play a significant role in theevolution of bird karyotypes, sometimes acting as one ofthe mechanisms of speciation . Recombination within the inversion loops inheterozygotes for inversion may lead to the formation ofchromosome fragments containing functional centromeres.One of such fragments could have become the ancestor ofGRC in songbirdsIt can be hypothesized that the proto-GRC became achromosome restricted to germ cells at the earliest stagesof its evolution. Many B-chromosomes exhibit genotaxis,accumulating in generative tissue and being deficient in somaticcells . The evolutionary significanceof this phenomenon is evident: it reduces the pressure ofnatural selection on genes localized on these chromosomes.However, the mechanisms underlying this phenomenonremain unknown.A.A. Torgasheva et al. (2019) suggested that the proto-GRC might already contain multiple copies of somatic genescontrolling the development and functioning of reproductiveorgans. Therefore, it could be selected for because it provideda higher dosage of these genes. This suggestion appearsplausible given the extreme economy of the avian genome. However, it is more likely that at thetime of its origin, the GRC was a typical B chromosome,i. e., an efficient parasite that ensured its transmission withoutconsidering the host\u2019s interests. Useful genes were probablycopied into the GRC at later stages of its evolution. The fewB-chromosome variants that persist in host genomes forextended periods and are widespread in populations becomegradually \u201cdomesticated\u201d acquiring properties beneficial tothe hosts .The question is what these properties are. By analogywith other examples of programmed DNA eliminationdiscussed above, it can be hypothesized that the GRC maycontain unique or amplified copies of the genes controllingearly development that exhibit antagonistic pleiotropy. Suchgenes may be necessary for early development, but theirexpression in later stages of life can be dangerous. In thatcase, the GRC can be considered the genetic equivalent ofa startup disk or a boot drive. Supporting this hypothesisis the discovery of the evolutionarily ancient gametologsbicc1, trim71, and puf60, the products of which may playimportant roles in embryonic cell differentiation and cellcycle control .Another class of genes that could have been evolutionarilyadvantageous when additional copies were created withinthe GRC are genes involved in the control of developmentand proliferation of germ cells , as well as in the regulationof synapsis and chromosome recombination .It has been suggested that the GRC may participate in sexdetermination and serve as the basis for a new system , whichhas already emerged or is emerging in the songbirds on topof the typical ZZ-ZW system found in all birds . However, I find this proposal highly questionable. AsI showed above, females with a single GRC exist and appearto develop normally, while certain males possess two GRCsin a significant portion of their germ cells.The suppression of recombination between the GRCs,along with the extensive trafficking between the GRCs andA-chromosomes, should lead to rapid incompatibilitiesbetween the genomes of closely related species. Followingthe Dobzhansky\u2013Muller model , it can be hypothesized that within each species, the emergingGRC variants are tested for compatibility with A-chromosomes,which already exhibit considerable homology dueto constant trafficking. We have already discussed that themechanisms underlying the massive trafficking of genesfrom A-chromosomes to the GRC remain unknown.Furthermore, we do not know the extent to which thistrafficking is unidirectional or if there is a reverse movementfrom the GRC to A-chromosomes. If the trafficking occursin both directions, the GRC may serve as a generator andincubator of new A-genes. 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Sex-chromosomeelimination in the bandicoot Isoodon macrourus usingY-linked markers. Cytogenet. Genome Res. 1998;81(1):54-59.DOI 10.1159/000015008.Weissman A. Prof. Weismann\u2019s theory of heredity. Nature.1890; 41(1058):317-323. DOI 10.1038/041317g0.Weissman A. The Germ-Plasm: A Theory of Heredity. NewYork: Charles Scribner\u2019s Sons, 1893."} +{"text": "The structure of diseases in humans is heterogeneous, which is manifested by various combinations of diseases, including comorbidities associated with a common pathogenetic mechanism, as well as diseases that rarely manifest together. Recently, there has been a growing interest in studying the patterns of development of not individual diseases, but entire families associated with common pathogenetic mechanisms and common genes involved in their development. Studies of this problem make it possible to isolate an essential genetic component that controls the formation of disease conglomerates in a complex way through functionally interacting modules of individual genes in gene networks. An analytical review of studies on the problems of various aspects of the combination of diseases is the purpose of this study. The review uses the metaphor of a hermeneutic circle to understand the structure of regular relationships between diseases, and provides a conceptual framework related to the study of multiple diseases in an individual. The existing terminology is considered in relation to them, including multimorbidity, polypathies, comorbidity, conglomerates, families, \u201csecond diseases\u201d, syntropy and others. Here we summarize the key results that are extremely useful, primarily for describing the genetic architecture of diseases of a multifactorial nature. Summaries of the research problem of the disease connection phenomenon allow us to approach the systematization and natural classification of diseases. From practical healthcare perspective, the description of the disease connection phenomenon is crucial for expanding the clinician\u2019s interpretive horizon and moving beyond narrow, disease-specific therapeutic decisions. We live in the \u201cMany Worlds in One\u201d and thisOne World amazes us with the mystery and the universalityof the connections of phenomena, the variety of evolutionaryand historical events. These events take place both on a cosmicscale and on a planetary scale and the Earthlings (humanity)are the same universality of connections between themselvesand the surrounding world. These connections are formednaturally or randomly, they have a long phylogenetic history of4 billion years and only a hundred-year ontogenetic history ofeach individual. The structure of \u201chuman\u201d connections, whichappears in metabolic and morphophysiological variability,forms the basis of medical assessments \u2013 the norm or thedisease. Since the beginning of the century, a new approach tothe study of these issues \u2013 the network analysis \u2013 has emergedin biology and medicine. The network analysis is an attemptto understand the laws governing all kinds of networks, fromthe social to the complex gene networks that rule over all cellsand traits, determining health or disease .The human genome, as the assemblage of all genes of theHomo sapiens species, is in a complex and not fully understoodrelationship with the environment and society. The peculiarityof such a relationship between genome and phenome is a differenceoften noted now: the genome is limited (approximately3 billion base pairs in humans), the phenome is not limited (itslimit depends on how far we want to go) .A century before the \u201cgenomic revolution\u201d took place, in the1930s, the outstanding Russian geneticist Alexander S. Serebrovskiy,discussing the problem of organic evolution, definedthis problem as an \u201cinfinite-finite contradiction\u201d in the \u201cunityof an infinite number of traits and a finite number of genes\u201d.In such an infinite world with an infinite number of traits,it is always possible to observe andidentify traits connected to each other, including those relatedto pathology. In the clinic, this phenomenon forms the basisfor diagnosis and healing, and stable combinations of certaindisease traits represent an independent subject of research \u2013the phenomenon of connection of diseases or the diseasesconnection phenomenon (DCP).In 1970, the American physician and specialist in the fieldof epidemiology of non-communicable diseases, Alvan R.Feinstein, proposed the term \u201ccomorbidity\u201d for combinationsof diseases in individuals. Comorbidity means the manifestationof an additional clinical condition that exists or occurs inaddition to the index disease under consideration . Such a clinical condition may be a disease, a pathologicalsyndrome, pregnancy, a long-term \u201cstrict\u201d diet, ora complication of drug therapy. Comorbidity is a complex ofseveral diseases that exist simultaneouslyin individual patients and are observed much morefrequently than would be expected in a random distribution.The popularity of the term \u201ccomorbidity\u201d is striking, especiallyamong clinicians: there is the International ResearchCommunity on Multimorbidity (IRCMo), the Journal of Multimorbidityand Comorbidity has been published since 2010, and thereis an online medical platform for discussing the diagnosisand treatment of patients with comorbid diagnoses (https://nexusacademy.ru/about). The author of the term \u201ccomorbidity\u201dis credited with the discovery that \u201cclarified\u201d the interpretationof comorbid pathology . And yet, there is stilla feeling of overestimation of \u201cclarity\u201d in the understandingof the phenomenon and the term. It is similar to the situationdescribed in the novel of the famous Nobel laureate WilliamFaulkner: \u201cThey all talked at once, their voices insistent andcontradictory and impatient, making of unreality a possibility,then a probability, then an incontrovertible fact, as people willwhen their desires become words\u201d(William Faulkner. The Sound and the Fury. 1929.)And yet, we must agree that the term \u201ccomorbidity\u201d hasproved especially successful for clinicians. It became an umbrellaterm for numerous names of combinations of diseases,variants of two or more forms of pathology in patients and,often, in their closest relatives. Sometimes such diseases arecalled background or concomitant diseases. In general, accordingto our calculations, the pool of names for such combinationsof diseases includes more than 30 terms. Among them:multimorbidity, polypathies, comorbidity, conglomerates,families, \u201csecond diseases\u201d and others. Most often there arediseases that have a \u201ccommon root\u201d , although other combinationsof diseases show nothing in common in pathogenesis . Note that specific terminologicalstudies are limited, and as a result we see no consensus . However, in the currentsituation the object of the study is defined, it is \u201ccomorbidpatient\u201d . Good quality clinical and epide-miologicaldata is accumulated, which came in time to becomethe basis for implementation of \u201comics\u201d approachesto research on the DCP problem. And there is very seriouscontent and a rather serious genetic aspect. This is the subjectof this article.Here we present a set (assemblage) of views connected with each other and forming a unified system,that is useful, in our opinion, for understanding of the DCP. Let us use a metaphor \u2013 the\u201chermeneutic circle\u201d \u2013 which describes the mutual agreementbetween the individual (part) and the whole, like a hermeneuticalrule: we must understand the whole in terms of the detail,and the detail in terms of the whole . If weconsider the DCP as a \u201cwhole\u201d, it would be reasonable toinclude as \u201cthe details\u201d (the components of the hermeneuticcircle) the fragments of concepts ofoutstanding clinical geneticists, such as the Soviet neurologistSergey N. Davidenkov (1880\u20131961), the American geneticistVictor A. McKusick (1921\u20132008), the German pediatricianMeinhard von Pfaundler (1872\u20131947) and the now livingGerman-American clinician John M. Opitz. All of them are,at the same time, geneticists and, most importantly, practicingphysicians who investigated the polymorphism of diseasemanifestation and the mysterious phenomenon of a combinationof several pathologies in one patient.Without keeping the chronological order of their publications,we follow the intended logic in presenting the structureof the hermeneutic circle, i. e., those \u201cdetails\u201d that can be usefulin interpreting the DCP as a \u201cwhole\u201d.\u201cLumpers\u201d and \u201csplitters\u201d . In the1960s, a discussion was opened in the medical genetics community\u2013 what is the \u201cnosology\u201d of genetic diseases? MainlyMendelian diseases were discussed, but also diseases withan inherited predisposition .Phenotypically, patients represent a huge clinical diversity, andpossibilities of clarifying the etiology of diseases by moleculargenetic or cytogenetic methods were limited in those years.So, physicians-researchers were quite free to classify the patientsby combining or separating them. However, during thediscussion of this problem, an important generalization wasproposed and it was the principles of medical genetics: pleiotropism,variability (polymorphism) and genetic heterogeneity. These principles, above all, can be consideredstabilizing the semantic context of understanding theDCP. Today\u2019s systematists of human pathology also rely onthese principles .Moreover, with the advances in genomic medicine, it becamepossible to describe the genetic architecture of multifactorialdiseases, which is understood as the number of genetic polymorphismsthat affect the risk of disease, the distribution oftheir allelic frequencies and their effect sizes, as well as theirgenetic mode of action .Syndrome as pleiotropy, conditional tropism hypothesis. The word \u201csyndrome\u201dwas first used in English in 1541, as noted by , and is still used to indicate a common cause rather thansimply a set of symptoms. The same authors also evaluateanother dictionary definition \u2013 the syndrome, as a concurrenceof manifestations \u201ccharacterizing a specific disease\u201d,a greater-than-chance concurrence of identical or very similarsets of manifestations in two or more individuals suggestingsimilar pathogenesis, subject to causal verification throughthe discovery of physical, infectious, toxicological, or geneticfactors .Today, biochemical and refined molecular/cytogenetic methodsidentify genetic causes, epigenetic modifications incombined phenotypes or syndromes with high accuracy. Theexplanation of such combinations, their persistence or \u201cdividing\u201din descendants, the severity of manifestations of similarcombinations, as well as the interpretation of the relationshipbetween multiple variations of the norm or minor anomalieswith their advanced forms of pathology was suggested bySergey N. Davidenkov in the conditional tropism hypothesis(1947). He used the evolutionary-genetic approach to analyzemore than one hundred nosological forms of human nervousdiseases. The frequency of combined appearance of the diseasesof the nervous system in one patient or in one familyis explained by conditional tropism: in addition to its owninfluence on the nervous system development, the pathologicalproperty (gene) also has the ability to dramatically enhancethe phenotypic expression of other genotype features \u201cmovinginto the same direction\u201d and including numerous variants. So,for example, a mild excavation of the foot can take the formof a severe Friedreich\u2019s deformity.Associations, syntropies and dystropies, the transitiveassociation hypothesis . The renowned textbook for the diagnosis of congenitaldiseases defines associations as combinationsof congenital anomalies that have no well-defined etiologyand occur together more often than expected by chancealone. Since its inception, the concept of \u201cassociations\u201d hasengendered feelings of unease and vagueness, as noted . They agreed on two variants in the definitionof the term: coincidental concurrence (simple rencontre orsimple juxtaposition) and combination of anomalies . In the 1900s,new designations of essentially the same associations appeared:but the term \u201cmultiple abarts\u201d was proposed for hereditary diseasesand congenital malformations, and \u201csyntropy\u201d (Syntropie inGerman) was proposed for commonmultifactorial diseases occurring in one patient at the sametime. They not only termed the \u201cmutual disposition, attraction\u201dof the two diseases by the term \u201csyntropy\u201d; in addition, on thebasis of abundant clinical data and tens of thousands autopsiesPfaundler and Seht recorded another pathological conditionopposite to syntropy \u2013 \u201cmutual repulsion\u201d, incompatibility and named it \u201cdystropy\u201d (Dystropiein German). At the same time, intermediate, to a certain extentrandom and \u201cneutral states\u201d also got their name, \u201cneutropy\u201d(Neutrotropie in German). According to these researchers, theterm \u201csyndrome\u201d can also be regarded as syntropy, becauseit means a \u201cselective relationship\u201d of its constituent traits.Another property of the unity of pathologicalconditions isthe appearance of at least two diseases in one patient at thesame time (synchrony). Thus, syntropy, syndrome, synchrony(\u201c3S\u201d) are related concepts and the main factor uniting themis a similar pathogenesis. For example, in relation to atherosclerosis,diabetes and obesity is a \u201ccommon root\u201d .In our current definition, syntropy is a natural-speciesphenomenon of a combination of two or more pathologicalconditions (nosologies or syndromes) in an individual andhis closest relatives, non-random and having an evolutionarygenetic basis; it is a part (an extract) of the human phenome,comprised of a landscape of interacting traits and diseases,reflecting continual molecular-genetic causality . The genes involved in the developmentof syntropies are called syntropic genes. More precisely,syntropic genes are a set of functionally interacting geneslocalized throughout the genome, coregulated and involved ina metabolic pathway common to a given syntropy . In the case when regulatoryrelationships lead to the mutual exclusion of certain phenotypesat the clinical level (dystropy), such genes are termeddystropic in relation to the relevant phenotypes. There is somesemantic similarity of the concepts of \u201csyntropic and dystropicgenes\u201d with the term \u201ccore genes\u201d, which were discussed inthe recently proposed omnigenic model of complex disease.Finally, let us talk about the transitive genetic associationhypothesis. The transitive associations are another form ofassociation from the described above, syntropy anddystropy (dissociation). David R. Blair et al. (2013) hypothesizedthat statistically significant comorbidities betweencomplex (MFDs) and Mendelian diseases represent a type ofgenetic association, in which a non-Mendelian phenotype ismapped to the genetic loci that cause the Mendelian disease.In fact, transitive associations are a kind of syntropy, butthe phenotype is the result of a combination of complex andMendelian disease. According to the authors of the hypothesis,such conditions represent about half (54 %) of all comorbiddiseases .Classification of variants of diseases connection in humans.There is no generally accepted classification of the DCP.Moreover, the tasks of systematization, understanding of thegeneral properties that fix regular connections, in all the varietyof such combinations, have not been formulated; the existingattempts to classify such pathological phenomena are stillfragmented and conditional. Most often, they are descriptivein nature. This is especially true for the clinical classificationof connections designated by the term \u201ccomorbidity\u201d,and carriers of such pathological features are referred to as\u201ccomorbidpatients\u201d . Now we can alsoconfirmthe attempts to systematize the concept of \u201csyntropy\u201d: by the mechanisms of formation , by the time ofoccurrence and by clinical significance .Previously, we proposed the identificationof the following forms of diseases connection in individualpatients . The proposed systematization of the DCPforms is also descriptive, but the elements of intrinsic classificationscan also be seen in it. This is associated, among otherthings, with the designation of the key terms of connectioncharacteristics: association and syntropy. There are severalsubject areas in scientific research (besides medicine), inwhich the term \u201csyntropy\u201d is used. Viktor B. Vyatkin (2016)designates three fields of science in which the concept of\u201csyntropy\u201d takes an important place, proposing a classificationof syntropy (in order of the beginning of their use)into: medical (Pfaundler \u2013 von Seht syntropy), biophysical(Fantappi\u00e8 \u2013 Szent-Gy\u00f6rgyi \u2013 Fuller syntropy), informational(Vyatkin syntropy). In our opinion, these two additional typesof syntropy not only have an independent significance, butare also important for the essential understanding of biologicalprocesses, including both in general pathology and in theparticular pathogenesis of the DCP.Note that the multiplicity of diseases in an individual is along-standing problem that had attracted the attention of researchersbefore the widespread use of the \u201ccomorbidity\u201d term.The commonality of the mechanisms of development of nonrandompathological connections is reflected in the names ofrelevant concepts: \u201cthe sum of homeostasis diseases\u201d , \u201cdiseases of adaptation\u201d , \u201ccardiovasculardisease continuum\u201d , \u201cmetabolicsyndrome\u201d . It is important to consider thisproblem from the genetic perspective, the concepts of diseasome and network medicine .Generalizations on the problem of studying the DCP allowus to approach the intrinsic classifications of the phenomenon.It is important. As Mikhail D. Golubovsky (2006) noted, agood system is an event in science, a conceptual discovery,a new vision of harmony in the chaos of facts. That is whythe inclusion of classifications in the hermeneutic circle seemsuseful.Syntropies (comorbidity)Syntropy is widespread and more common than we imagine.For example, the 438 common diseases registered in theUK Biobank patient histories (https://www.ukbiobank.ac.uk/)form more than 11,000 possible combinations . The global nature of the problem has initiated a hugenumber of studies, mainly of an epidemiological kind. In 2021alone, the query \u2018comorbidity\u2019 found 34,185 medical andbiological articles in the US National Center for BiotechnologyInformation database (https://pubmed.ncbi.nlm.nih.gov/).Currently, more than 50 million people aged 65 and older \u2013nearly half of Europe\u2019s population \u2013 have two or more diseasesat the same time . The number of comorbidpatients is predicted to continually increase, affecting up to68 % of the population by 2035 .Molecular causes of phenotypic connections remain largelyunknown, despite active research in this field . Through these studies, it became evidentthat a significant proportion (46 %) of comorbid conditions iscaused by a common component at the level of genes, SNPs,and gene networks interactions , that ingeneral reflects their pathogenetic relationship. For example,the HLA-DQB1, TLR1, WDR36, LRRC32, IL1RL1, GSDMA,TSLP, IL33, SMAD3 genes involved in the pathogenesis ofcertain allergic diseases are critical for the development ofphenotype according to the \u201catopic march\u201d scenario . Meanwhile, in terms of pathogenesis, seeminglynon-obvious connections between diseases are revealed. Theexistence of many of these connections was not previouslyeven assumed. Varicose veins disease, according to genetic correlations analysis, is associated with fluid intelligence,prospective memory and educational attainment , and autism is positively correlated with allergicrhinitis and autoimmune disorders .A significant addition to the identification of common genesfor comorbid conditions is the study of the biological processesin which these genes are involved .The use of such approaches provides a more complete pictureof the connections of diseases and common pathogeneticpathways. Knowledge of these connections can be widelyapplied, including treatment of comorbid patients.Based on our own research findings on the genetic componentof allergic diseases on the onehand, we established the molecular connection of most allergicdiseases. On the other hand, with regard to the molecular relationshipsof allergic diseases with other diseases, we notedtheir proximity to infectious diseases and a marked distancefrom autoimmune diseases .The TLR4, CAT, ANG/RNASE4 genes can make the greatestcontribution to the comorbidity of bronchial asthma andhypertension, indicating the importance of inflammation,neovascularization and oxidative stress for the pathogenesisof both diseases . The development ofbronchial asthma phenotypes in combination with cardiovascular/metabolic disorders is associated with certain geneticvariants that affect gene expression, including CAT, TLR4,ELF5, ABTB2, UTP25, TRAF3IP3, NFKB1, LOC105377347,C1orf74, IRF6 and others, in the target organs of the studieddisease profile .Syntropic genes are involved in pathogenesis through complexinteractions with other genes, proteins, and environmentalfactors, which collectively affect the clinical manifestationsof comorbidities. In most cases, abnormalities in syntropicgenes are localized mainly in non-coding RNAs and intergenicregions functionally associated with the regulation ofgene transcription . In turn, the transcriptionof syntropic genes depends on epigenetic mechanisms,in particular DNA methylation , whichindicates a modifying role of environmental influences oncomplex phenotype development.Many syntropic genes are known drug targets for therapy,in particular allergic ,bronchopulmonary and cardiovascular diseases .More than eight thousand drugs target genes involved in thedevelopment of comorbid conditions .Theoretically, such results not only highlight the importantcontribution of genes to phenotypic correlations, but alsoprovide an opportunity for drug repurposing to target commongenetic components of syntropic diseases.Dystropies The contrast for syntropy is the diseases that manifest bythe phenotypic conflict of one pathological condition withanother (dystropy). Dystropy affects various diseases includingimmune, oncological, neurodegenerative, cardiovascular,autoimmune and others. The spectrum of molecularmechanisms underlying this phenomenon also seems to bevery diverse. Research on dystropy focuses on the search formolecular and genetic differences between the diseases. As aresult of these studies, differences in the transcription of thesame genes in different diseases have been established. Usingthe example of oncological and neurodegenerative diseasesdystropy , it was revealed that differentiallyexpressed genes are mainly associated with DNArepair, mitochondrial function, stabilization of p53, regulationof angiogenesis, cell cycle, metal ion transport, glucosetransport, regulation of apoptotic processes, myeloid leukocyteactivation and phagocytosis, mTORC1 and KRAS signaling. Transcriptionalchanges in oncogenesis are highly variable; some genes maybe activated in some forms of cancer, but suppressed in others,which is probably associated with the features of complexgenetic and epigenetic disorders . At thesame time, common patterns are recorded. In particular, Ib\u00e1\u00f1ezet al. (2014) identified the genes MT2A, MT1X, NFKBIA,AC009469.1, DHRS3, CDKN1A, TNFRSF1A, CRYBG3, IL4R,MT1M, FAM107A, ITPKC, MID1, IL11RA, AHNAK, KAT2B,BCL2, PTH1R, NFASC that are simultaneously activated inseveral disorders of the central nervous system but are suppressedin oncological diseases.The examples above indicate that phenotypic suppression ismediated by genetic factors. In some cases, potentially \u201charmful\u201dalleles can be beneficial, creating some kind of trade-offbetween an increased risk of developing certain diseases anda low risk of developing others. Trade-offs are inevitable, because the complex integrated functioning of the wholeorganism needs several interacting parts to work togetherto perform certain functions. Such integration can lead toa dilemma often called the \u201ccost of complexity\u201d , resulting from multiple interacting parts workingtogether to successfully perform a function. Alteration of anypart will inevitably negatively affect other features, alteringfunction and reducing overall performance or fitness. Thus,the mechanistic basis for the trade-offs may be focused onpleiotropic genes involved in the biological pathways sharedbetween different traits . In accordancewith this suggestion, the observed divergent natureof the transcription of some genes thought to be importantfor dystropy can be expected. Diametrical disorders havethe intrinsically bidirectional nature of biological processes,whereby expression or activation of genes can be increasedor decreased from some optimal value .Dystropy is significantly formed by drug therapy, becausedrugs can be connected with the regulation of common molecularprocesses of phenotypically polar diseases. For example,the use of anticholinesterase agent galantamine and the selectivemonoamine oxidase inhibitor selegiline in neurodegenerativediseases has anticancer effects . Two drugs for breast cancer therapy(exemestane and estradiol) reduce the risk of Alzheimer\u2019sdisease and other dementias .Transitive genetic associationsGenes that can harbor mutations underlying rare and highlypenetrant Mendelian diseases affect the development of morecommon forms of diseases. The effect of mutations can beeither a predisposing factor for disease development or viceversa, a suppressor of phenotype manifestations. There arevarious estimates of the involvement of Mendelian genes inthe phenotypic expansion of multifactorial pathology. About300 genes associated with common diseases in genome-widestudies underlie a number of Mendelian diseases . By some estimates, the proportion of Mendelian genesin the structure of multifactorial diseases is approximately23 % , but with the growth of genomewidesequencing data, this amount is likely to increase significantly.In terms of specific pathology, 11 out of 30 genes associated with serum lipoproteinconcentrations are involved in monogenic disorders of lipidmetabolism . These genes, whichare causative variants of both Mendelian disorders and therisk of multifactorial diseases, tend to have higher functionalsignificance and higher expression levels than genes only associatedwith common diseases. Furthermore, genetic variantsin conditionally \u201cMendelian\u201d genes tend to present higherodds ratios than variants on genes with no link to Mendeliandisorders .The idea of a mutational burden materialization in commonpathology is not new. The experimental basis for thisphenomenon was the publication of Michael S. Brown andJoseph L. Goldstein , which showedthat patients with heterozygous mutations in the low-densitylipoprotein receptor (LDLR) gene, along with familial hypercholesterolemia,have coronary atherosclerosis and myocardialinfarction. In 2013, David R. Blair formulated a hypothesis about the transitivity of rare Mendelianvariants into a pathological \u201callelic continuum\u201d in a widerange of final phenotypic effects from monogenic to complexmultifactorial diseases. To date, extensive factual materialhas been accumulated to support this hypothesis. Carriers ofFLG gene mutations associated with loss of filaggrin functionhave an increased risk of developing atopic dermatitis and bronchial asthma in the contextof atopic dermatitis, while at the same time the risk of asthmawithout atopic dermatitis is reduced . Thisfinding suggests that FLG gene mutations are an importantrisk factor for atopy in general, but with different chances fora particular phenotype. Carriers of Gaucher disease mutations,mainly L444P and N370S in the glucocerebrosidase(GBA) gene, have an increased risk of Parkinson\u2019s disease. Heterozygous carriers of mutationsin the cystic fibrosis transmembrane regulator (CFTR) geneare predisposed to idiopathic chronic pancreatitis and chronic obstructive pulmonary disease .Various approaches are used to gain knowledge about theactive contribution of Mendelian disease genes as causativegenes for multifactorial diseases. For example, based on theprioritization of data from genome-wide associative studiesof various forms of cardiomyopathies, it was found that 70 %of the hypertrophic and 56 % of the dilated cardiomyopathygenes are associated with various Mendelian diseases. Thisfinding suggests that the existing dichotomous classificationof diseases \u2013 monogenic and multifactorial \u2013 has becomeirrelevant and requires rethinking taking into account newknowledge about the genetic structure of susceptibility .The potential of separate gene mutations is evaluated as protectivefactors in relation to oncological diseases. In particular,activation of apoptosis and autophagy by mutant huntingtin, as well as the oncotoxic function ofCAG repeats , the expansion of whichcauses the Huntington\u2019s disease, may prevent the developmentof most types of cancer in patients with this hereditary disease. The molecular oncoprotective mechanismof the Laron dwarfism mutation (OMIM #262500)(NM_000163.5(GHR):c.594A>G (p.Glu198=)) in the growthhormone receptor gene is mediated by effects on the activityof genes involved in the control of the cell cycle, mobility,growth and oncogenic transformation .Loss of function of individual proteins due to loss-offunctionmutations provides specific resistance against somecommon phenotypes. Protection against type 2 diabetes isassociated with carrying a mutation in the zinc transportertype 8 gene (SLC30A8) that leads to the synthesis of a truncatedprotein . As a consequence ofthe resulting deficiency of SLC30A8 gene function throughthe mechanism of haploinsufficiency, carriers of mutant alleleshave better insulin secretion due to increased glucose sensitivity and proinsulin conversion in the pancreatic betacells. Another example relates to nonsense mutations in the proprotein convertase subtilisinkexintype 9 (PCSK9) gene underlying familial hypercholesterolemia(OMIM #603776); these mutations result inlower low-density lipoprotein cholesterol level . Heterozygous carriers of F508del in the cystic fibrosistransmembrane regulator (CFTR) gene, which causes cysticfibrosis, are more resistant to infectious diseases such as cholera,typhoid fever and tuberculosis. Therefore, some authorsattribute the high prevalence of cystic fibrosis in the modernhuman population to the adaptive advantage of mutation carriers.The results of the classification of some multifactorial andMendelian diseases based on the genes associated with themhave identified a large common genetic component of multifactorialdiseases . Monogenic diseases are expectedlydistant from them, with the exception of Huntington\u2019s disease,which is not only close to other neurodegenerative diseasesin the degree of gene commonality, but also has molecularsimilarities with infectious, autoimmune, and cardiometabolicdiseases . Overall, in terms of the degree ofgenetic \u201ccommonality\u201d and clustering, most of the diseasesstudied reflect the generally accepted classification of diseases.However, such modeling has a limitation, since it depends onthe extent to which genes are studied, so we should expecta shift in the location of monogenic diseases. At present, theamount of genomic information is rapidly expanding, whichbrings us closer to filling the gap in the knowledge aboutdisease-associated genes. But even after this gap is filled, amore difficult task remains: to understand the mechanismsof manifestation of the mutation effect and to map the geneticinteractions of mutations in different genes, which arecombined in a certain way due to structural and molecularinteraction , contributing to phenotypicdiversity.The last decades have been an important milestone for genomicresearch due to the possibilities of high-throughputtechnology and the enormous amount of data obtained. It isexpected that between 100 million and 2 billion human genomescould be sequenced by 2025, far exceeding growth inother dynamically developing fields that generate Big Data:astronomy, YouTube and Twitter .The authors of the aforementioned paper compare genomicresearch to a \u201cfour-headed beast\u201d based on four main demandsin genomics throughout the life cycle of the datasetsgenerated by sequencing \u2013 acquisition, storage, distribution,and analysis . Of these four demands,the greatest effort is required to analyze and comprehend theresults obtained, to unravel the complex relationship betweengenetic variants and phenotypes. This relationship is to a largeextent a stochastic process, limited by the genome on the onehand and environmental factors on the other. Consequently,rational ways to comprehend biologically complex objects inthe world of Big Data are still relevant.The results of the study of the diseases connection phenomenon accumulated in thescientific literature lead to the necessity and possibility of approachingsuch a vision of generalization, which was outlinedby the outstanding Carl R. Woese in his paper: \u201c...the essenceof biology lies not in things as they are, but in things cominginto existence\u201d . In this context,our article attempts to consider the diseases connection phenomenonwithin the framework of the \u201chermeneutic circle\u201dmetaphor. It is important to note the historical continuity ofscientific knowledge on the issue, which was originally basedon a holistic view of the development of living organisms,ranging from \u2018Geoffroyism\u2019 (named after \u00c9tienne GeoffroySaint-Hilaire), reflected in the principles of connexion, theunity of elementarity and integrity , tothe manifestation of the complex tropism of hereditary factors and the principles of systematization inmedical genetics , and finally to the frameworkof modern concepts of network biology and medicine.The progress of research on comorbidities has shown theinsufficiently comprehensive nature of the existing terminology.For example, in contrast to the term \u201ccomorbidity\u201d,which has become familiar in medical practice, the geneticdiscourse of the proximity of concomitant diseases is mostfully interpreted by the terms \u201csyntropy\u201d and \u201cdystropy\u201d, reflectingthe peculiarities of pathogenetic relationships betweendiseases. The pathogenetic principle of gene involvement inthe development of comorbid diseases allowed to classify themas syntropic and dystropic genes . Important inthis context is the classification of genes on a mechanistic basisinto nuclear/core and peripheral genes, that have omnigeniceffects on the development of the pathological phenotypethrough trans- and cis-regulation . It is obvious that, along with nuclear genes, peripheralgenes are important objects for MFDs comorbidity studies,because their global activity in specific cell types determinescellular function and disease risk.The molecular nature of comorbidities, which allows themto be connected in many, often non-fatal and even beneficialcombinations, remains difficult to explain due to some \u201clibertiesof genome\u201d determined by the dynamic and non-linearnature of the functioning of the system, regulated by feedbacksthat can be disrupted in predictable but individual way. Thedegree of benefit or harm of such combinations of diseases ofthe conditional \u201cadaptive phenotype\u201d depends on the tradeoffsthat are most obvious due to competition for the limitedresources of the organism. Probably, vulnerability to somediseases with a relatively low risk of developing others isreduced to the establishment of some \u201cprice of complexity\u201d,based on the pleiotropic action of genes.Thus, the diseases connection phenomenon, described inclinical practice for a long time, is of independent interest forfundamental research. The DCP also becomes an additionalway to elucidate the etiology and pathogenesis of complexdiseases, in the study of which modern methodological andconceptual approaches are involved. On the other hand, thediseases connection phenomenon is important for practicalhealthcare, since its description is crucial for expanding theclinician\u2019s interpretative horizon and moving beyond narrow,disease-specific therapeutic decisions. 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Conv-Former: A Novel Network Combining Convolution and Self-Attetion for Image Quality Assessment. The original [29] becomes the current [31]:29.IEEE Signal Process. Lett.2013, 20, 209\u2013212.Mittal, A.; Soundararajan, R.; Bovik, A.C. Making a \u201cCompletely Blind\u201d Image Quality Analyzer. The original [30] becomes the current [29]:30.IEEE Trans. Neural Netw.2011, 22, 793\u2013799.Li, C.; Bovik, A.C.;Wu, X. Blind Image Quality Assessment Using a General Regression Neural Network. The original [31] becomes the current [30]:34.Sensors2022, 22, 9696.Varga, D. No-Reference Video Quality Assessment Using the Temporal Statistics of Global and Local Image Features. The original [32] becomes the current [34]:32.Netw. Comput. Neural Syst.1994, 5, 517\u2013548.Ruderman, D.L. The Statistics of Natural Images. The original [33] becomes the current [32]:33.IEEE Trans. Inf. Theory1992, 38, 587\u2013607.Simoncelli, E.P.; Freeman, W.T.; Adelson, E.H.; Heeger, D.J. Shiftable Multiscale Transforms. The original [34] becomes the current [33]:A correction has been made to \u201cOrder of references\u201dRuderman et al. found that the luminance of natural image normalization tends to follow a normal (Gaussian) distribution [32]. They posit that the distortion of an image changes the statistical characteristics of the normalization coefficient. By measuring the changes in the statistical characteristics, the distortion type can be predicted and the image visual quality can be evaluated [33]. Based on this theory, Mr. Mittal put forward the BRISQUE algorithm [28], which is based on the image spatial statistical characteristics. Ronin Institute et al. apply a broad spectrum of statistics of local and global features to characterize the variety of possible video distortions [34].The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Single nucleotide polymorphisms (SNPs) are the most common type of variation in the human genome. The vast majority of SNPs identified in the human genome do not have any effect on the phenotype; however, some can lead to changes in the function of a gene or the level of its expression. Most SNPs associated with certain traits or pathologies are mapped to regulatory regions of the genome and affect gene expression by changing transcription factor binding sites. In recent decades, substantial effort has been invested in searching for such regulatory SNPs (rSNPs) and understanding the mechanisms by which they lead to phenotypic differences, primarily to individual differences in susceptibility to diseases and in sensitivity to drugs. The development of the NGS (next-generation sequencing) technology has contributed not only to the identification of a huge number of SNPs and to the search for their association with certain diseases or phenotypic manifestations, but also to the development of more productive approaches to their functional annotation. It should be noted that the presence of an association does not allow one to identify a functional, truly disease-associated DNA sequence variant among multiple marker SNPs that are detected due to linkage disequilibrium. Moreover, determination of associations of genetic variants with a disease does not provide information about the functionality of these variants, which is necessary to elucidate the molecular mechanisms of the development of pathology and to design effective methods for its treatment and prevention. In this regard, the functional analysis of SNPs annotated in the GWAS catalog, both at the genome-wide level and at the level of individual SNPs, became especially relevant in recent years. A genome-wide search for potential rSNPs is possible without any prior knowledge of their association with a trait. Thus, mapping expression quantitative trait loci (eQTLs) makes it possible to identify an SNP for which \u2013 among transcriptomes of homozygotes and heterozygotes for its various alleles \u2013 there are differences in the expression level of certain genes, which can be located at various distances from the SNP. To predict rSNPs, approaches based on searches for allele-specific events in RNA-seq, ChIP-seq, DNase-seq, ATAC-seq, MPRA, and other data are also used. Nonetheless, for a more complete functional annotation of such rSNPs, it is necessary to establish their association with a trait, in particular, with a predisposition to a certain pathology or sensitivity to drugs. Thus, approaches to finding SNPs important for the development of a trait can be categorized into two groups: (1) starting from data on an association of SNPs with a certain trait, (2) starting from the determination of allele-specific changes at the molecular level (in a transcriptome or regulome). Only comprehensive use of strategically different approaches can considerably enrich our knowledge about the role of genetic determinants in the molecular mechanisms of trait formation, including predisposition to multifactorial diseases. One of the main tasks of human genetics is to clarify themechanisms by which genome variations lead to phenotypicdifferences, primarily to individual differences in susceptibilityto diseases and in sensitivity to drugs. Single-nucleotidepolymorphisms (SNPs) are the most common type of genomevariation . Currently, due to the developmentof next-generation sequencing (NGS) technologies, morethan 950 million SNPs of the human genome are registeredin database dbSNP (https://www.ncbi.nlm.nih.gov/projects/SNP/snp_summary.cgi) ; furthermore,rare SNPs with a frequency ofless than 1 % constitute more than 90 % of the total numberof SNPs. It seems unlikely that the vast majority of identifiedvariations can be important for the phenotype, but some ofthem certainly form the genetic basis of phenotypic traits,including predisposition to various diseases. In recent decades,major efforts have been applied to the search for such SNPs.The most popular approach (which started back in the1980s) to the identification of trait-related SNPs has been thedetermination of associations with diseases for SNPs foundin candidate genes , and in this context, only SNPs affecting the proteincodingpart of a gene have been investigated .Somewhat later, there has been some interest in elucidatingthe functionalityof variants located in noncoding regions ofgenes, i. e., in determining an effect of such variants on a certainmolecular phenotype. In particular, it has been shown thatsuch SNPs affect transcription factor-binding sites (TFBSs),thereby leading to changes in the expression of the respectivegenes . Nonetheless, these fewfunctional studies have remained almost invisible against thebackdrop of a huge wave of research aimed at identifying associations.The productivity of detection of disease-associated SNPsincreased dramatically with the advent of the genome-wideassociation study (GWAS) technology in the mid-2000s, which is based on an unbiased \u2013 not based on anyideas about the formation of a trait \u2013 principle of a genomewidesearch for SNPs associated with the trait . To date, more than 72 thousandassociations of genetic variants with traits have been foundby GWASs ,thus allowing to find many new genes and systems of genesassociated with predisposition to various diseases .Nevertheless, GWAS technology does not provide any informationabout the functionality of the detected variants,thereby making it very difficult to elucidate the molecularmechanisms underlying the development of a pathologyand hence to develop effective methods for its treatment andprevention. Additionally, based on results of GWASs, it isalmost impossible to distinguish a truly disease-associatedvariant from the many marker variants that are detected due tolinkage disequilibrium . It is also known that most SNPs identifiedby GWASs are located in the noncoding part of the genomeand, as a rule, in its regulatory regions ; these data implyan influence of such SNPs on the binding of transcription factors(TFs) and on gene expression. Thus, a need for researchon functional interpretation of data from GWASs \u2013 both at the level of individual potentially regulatory SNPs (rSNPs)and at the level of all such variants collectively \u2013 has becomeobvious. In addition, because the GWAS technology greatlyunderestimates the actual number of associations owing tothe required strict thresholds in statistical processing , investigators have recognized the need to developGWAS-unrelated large-scale function-based approaches tothe search for rSNPs .timing of emergence is analysis ofexpression quantitative trait loci (eQTLs) . Thisanalysis, by means of transcriptome data , determinesfor each SNP a difference in the level of expression of individualgenes among homozygotes and heterozygotes fordifferent alleles of this SNP . Somewhat later, techniques were devisedfor finding allele-specific events both in data from RNA-seq and in data from ChIP-seq,DNase-seq, and ATAC-seq . Massivefunction-based approaches also include massively parallelreporter assay (MPRA), SNP-seq, and SNP-SELEX .At the beginning of this review, using the latest studies asexamples, we examine rSNPs that are (i) associated with thedevelopment of pathologies according to results of GWASsand are (ii) characterized in detail in terms of their influenceon an interaction with a TF and on the expression of nearbyor distant genes. Next, the review describes the application offunctional genomics methods to interpretation of data fromGWASs and to the search for new regulatory variants withoutGWASs. In the course of the presentation, strengths and weaknessesof these approaches are shown, as is the importanceof comprehensive use of GWASs and functional genomicsmethods to reveal the role of SNPs in molecular aberrationsunderlying the development of a pathology.A wide range of experimental methods are utilized to functionallystudy individual possible rSNPs. At initial stages,classical methods are usually used: analysis of DNA-proberetardationin a gel by nuclear extract proteins and a reporter assay , which allow a researcher to detect aninfluence of an SNP on the binding of some TF or on reportergene expression, respectively . To identify the TFs the binding sites of which areaffected by nucleotide substitution, scientists perform EMSAusing appropriate antibodies or purified TFs , chromatin immunoprecipitation with detection of alleleasymmetry in a PCR product (ChIP-AS-qPCR) , and mass-spectrometric analysis of proteins isolatedfrom complexes with oligonucleotides containing minor alleles.An impact of a nucleotide substitution in the identifiedTFBSs on their potential target genes is confirmed by experimentswith downregulation or artificial upregulation ofgenes of the corresponding TFs or by studying the effect ofpoint mutations introduced into the TFBS using CRISPR/Cas9 technology . Lately, an increasingly popularapproach in this field of research on SNPs has also been thedetermination of allelic imbalance of the expression for SNPslocated in transcribed regions of genes. Nonetheless, it is worthnoting that such an SNP can be either an rSNP proper or a marker SNP in a linkagegroup with an rSNP located in a nontranscribed region .Various combinations of these techniques are employed inmodern research, as illustrated by the examples below.A textbook example of a well-studied rSNP is rs36115365(G/C), which is situated at a locus associated with varioustypes of cancer according to data from GWASs (chr5p15.33:region 2). At this locus, a correlation analysis has revealednine SNPs associated withpancreatic cancer, testicular germ cell tumor, lung cancer, andmelanoma. To screen all nine SNPs for regulatory activity,EMSA and reporter assay were performed by means of eighthuman cell lines . The use of several celllines is a common practice in such studies and is aimed at the highest possiblecoverage of events of interaction of TFs with their bindingsites; the reason is substantial differences in the sets of TFs expressedin different cell types . The screeninganalyses identified only SNP rs36115365 as potentiallyregulatory, and its C allele showed both much better binding toa certain protein in the EMSA and greater activation of reportergene expression as compared to the G allele .rs36115365 is located ~18 kilobase pairs (kbp) upstreamof the start of the TERT gene (encoding reverse transcriptaseof the telomerase complex) and approximately 5 kbpdownstream of the end of the CLPTM1L gene. Accordingto the results of ChIP-seq (chromatin immunoprecipitationfollowed by sequencing of DNA from the precipitates) fromproject ENCODE , this SNP\u2019s locationoverlaps with many TFBSs, and this region is enriched withactive chromatin histone marks, which is typical for enhancerregions. Inactivation of this region by small-interfering-RNAmediatedtranscriptional silencing results in downregulation of only the TERT gene. To identifythe TF the binding site of which changes as a consequenceof the substitution of G with C, the binding of proteins fromnuclear extracts to oligonucleotides containing minor alleleswas implemented, followed by mass-spectrometric analysis ofthe bound proteins. After an analysis of the obtained peptides,four TF candidates that prefer the C allele were proposed:ZNF148, VEZF1/ZNF161, ZNF281, and ZNF740. In EMSAinvolving specific antibodies to these TFs, only ZNF148 wasconfirmed, which was subsequently verified by means ofthe purified ZNF148 protein in an experiment. A small-interfering-RNA-mediated knockdown of ZNF148 gave a de-finitiveanswer because it reduced TERT expression and telomeraseactivity and shortened telomere length. Thus, theC allele corrects the binding site of ZNF148, enhances theexpression of TERT and, as a consequence, increases the riskof carcinogenesis .According to GWASs, rs174575 (C/G) correlates with anelevated risk of colorectal cancer . ThisSNP is located in the first intron of the delta-6-desaturasegene (FADS2) at a distance of +41.5 kbp from its transcriptionstart site and at a distance of \u2013178.8 kbp from the transcriptionstart site of the gene of long noncoding RNA AP002754.2.The rs174575 region in chromatin is enriched with histonemodifications characteristic of active regulatory regions, and judging by DNaseseqdata (identification of sites of hypersensitivity to DNase I)and findings of ATAC-seq (assay for transposase-accessiblechromatin), corresponds to open chromatin (ENCODE). Thehypothesis of a regulatory role of rs174575 is supported byeQTL analysis data, which show an association of the G allelewith overexpression of FADS2 and AP002754.2.Computer analysis of DNA motifs using Web services Cistrome and JASPAR has revealed that in the case of rs174575, the replacement ofG with C damages the binding site of TF E2F1, and the dataof ChIP-seq from ENCODE, obtained on colorectal cancerLoVo cells, indicate that E2F1 is mapped to the location ofthis SNP. A cross-competitive EMSA has confirmed betterbinding of a certain nuclear extract protein to the G allele,and that this protein is E2F1 has been demonstrated by ChIPqPCRwith appropriate antibodies. For instance, in cell lineswith different genotypes \u2013 HCT116 (CG), SNU-C1 (CG), andHT115 (CC) \u2013 a stronger binding of E2F1 is observed in cellscarrying the G allele. A study involving reporter constructs hasalso confirmed a higher enhancer activity of a DNA fragmentcontaining the G allele .Direct contact between the region containing rs174575 andpromoters of FADS2 and AP002754.2 has been detected by thechromosome conformation capture (3C) method, and it turnedout that the interaction was much more pronounced in cell linescarrying the G allele. Further experiments indicated that overexpressionof AP002754.2 sharply raises the level of FADS2expression in HCT116 and LoVo cells, and a knockdown ofAP002754.2 by microRNA causes a decrease in the expressionof this gene, indicating a stimulatory role of AP002754.2 inthe regulation of the FADS2 gene. On the other hand, overexpressionof FADS2 or AP002754.2 significantly increasesthe proliferation rate of HCT116 and LoVo cells, whereas aknockdown of FADS2 or AP002754.2 significantly reducesit. It has also been shown that overexpression of FADS2 andAP002754.2 accelerates tumor growth in in vivo experimentsin mice. It is known that the product of the FADS2 gene is a keyenzyme in the biosynthesis of polyunsaturated fatty acids,including arachidonic acid, which in turn is a precursor ofprostaglandin E2 (PGE2), which promotes tumor growth andmetastasis. Thus, rs174575 acts as an allele-specific enhancerthat stimulates the transcription of FADS2 and AP002754.2,leading to an elevated risk of colorectal cancer in the case ofthe G allele .According to GWASs, rs4903064 (T/C) is associated withrenal cell carcinoma, the most common type of kidney cancer. rs4903064 is located in the third intronof the DPF3 gene, which encodes a protein of the BAF subfamilyof the SWI/SNF chromatin-remodeling complex. Thepredominance of the C allele of rs4903064 in tumor tissuesamples from patients with clear-cell renal carcinoma hasbeen demonstrated, in contrast to both normal kidney tissuesand tumor tissue from individuals with papillary renal cellcarcinoma and individuals with chromophobe renal cell carcinoma.In this context, a measurement of the ratio of alleles inDPF3 pre-mRNA in patients with clear-cell renal carcinomaheterozygous for rs4903064 has confirmed a skew toward theC allele .According to ATAC-seq data obtained on primary renalcancer cells, rs4903064 is located in an open chromatinregion, in a putative enhancer. Given that the substitution ofT with C (rs4903064) creates a potential binding site for TFHIF, a reporter analysis has been performed on HeLa andMCF-7 cell lines, showing that an increase in reporter geneexpression takes place only in the case of the C allele andonly when cells are treated with a specific stabilizer of HIF:dimethyloxalylglycine. Knockouts of various isoforms ofHIF have revealed that the increase in reporter activity uponstimulation with dimethyloxalylglycine depends on HIF-1\u03b1.By means of ChIP-qPCR in primary renal tubular cells withdifferent genotypes of rs4903064 , enhancedbinding of HIF-1\u03b1 and HIF-1\u03b2 to risk allele C has been confirmed.To elucidate the role of overexpression of DPF3 inthe development of clear-cell renal carcinoma, a knockout ofDPF3 has been performed in cells of proximal renal tubulesusing CRISPR/Cas9 technology. It was demonstrated in thatreport that cells with defective expression of DPF3 grow moreslowly than control clones of the corresponding cells, suggestingthat increased expression of DPF3 in proximal tubule cellsstimulates proliferation .rs17114036 (T/C) is associated with coronary heart diseaseand ischemic stroke according to GWASs . This SNP is located in the 5th intron of the PLPP3gene, encoding phospholipid phosphatase 3, which inhibitsinflammation of endothelium and contributes to the integrityof its monolayer.Experiments with ATAC-seq and ChIP-seq (H3K27ac andH3K4me2)performed on human aortic endothelial cells(HAECs) have identified the region containing rs17114036 asa potential enhancer. The enhancer activity of this region wasconfirmed by reporter analysis, whereas protective allele C significantly increased the activity ofluciferase upon transfection of vector constructs into HAECs.A deletion of a 66-bp region containing rs17114036 by meansof CRISPR/Cas9 significantly reduced the expression ofPLPP3 as compared to the unedited genome and enhanced thepermeability of the monolayer of edited HAECs. As a result ofmodeling hemodynamic processes, an increase in the activityof the studied enhancer in HAECs wasshown with an 18-hour \u201catheroprotective\u201d flow as comparedto an \u201catherogenic\u201d flow, while no effect of the T allele wasfound. It turned out that the substitution of the T nucleotidewith C creates a binding site (CACC) for the KLF2 protein,as confirmed by ChIP-AS-qPCR analysis in HAECs heterozygousfor rs17114036. Cotransfection experiments with aplasmid causing overexpression of KLF2 also showed higherluciferase activity in the case of the tested enhancer carryingthe C allele .rs4407214 (T/G) is associated with estrogen receptor-negativebreast cancer. In the HMEC cell line, an analysis of ChIP-seqdata from the ENCODE project regarding locations of marksof active chromatin has helped to find in the rs4407214 region a regulatorylocus in intron 1 of the WDR43 gene .By EMSA, the researchers showed ASB of nuclear proteinsfrom MCF10A and CAL-51 cells to DNA probes mimickingthe region of this SNP\u2019s location in the genome. Reporter geneexpression under the control of the identified regulatory regionon the same cell lines was also found to be allele-dependent.Bioinformatic analysis was then performed using theJASPARdatabase and available ChIP-seq data for this regionfrom the ENCODE project to identify the TFs the bindingsitesof which are altered by the G-to-T substitution (rs4407214).As a result, USF1 was identified as such a TF. A competitiveEMSA with nuclear proteins isolated from CAL-51 andMCF10A cells confirmed the ASB of USF1 in the case ofthe G allele. It was also demonstrated that CRISPR/Cas9-mediated removal of the presumed regulatory region containingrs4407214 results in underexpression of PLB1 (phospholipaseB1), which is located at a distance of ~400 kbp fromWDR43.Because results of GWASs tend to associate a trait (disease)with multiple loci , mostof which in turn contain many often coinherited SNPs , it is very difficult tochoose among them the potential rSNPs involved in a disease\u2019spathogenesis. To date, several effective experimental solutionsto this problem have been developed. First of all, these arescaled up versions of the approaches utilized to investigateindividual rSNPs: a reporter assay (MPRA) and methods forstudying protein\u2013nucleic acid interactions .In particular, MPRA has been successfully used to find therSNPs that play a key role in the genetic predisposition tolupus erythematosus . According to GWASfindings, 3,073 SNPs in 91 loci are associated with this disease.Those researchers constructed a barcoded library containing12,396 170-bp oligonucleotides containing in the middle allknown variants of these 3,073 SNPs; these oligos were insertedupstream of a minimal promoter placed before the eGFP gene.An influence of a minor allele on enhancer activity of insertsfor 51 SNPs from 27 loci was demonstrated in the GM12878cell line. The small number of identified rSNPs can most likelybe explained by transfection of only one cell line; if severalcell lines had been tested, the number of rSNPs would havebeen much larger due to expansion of the set of TFs involvedin the study. Similarly, in MPRA, 30 out of 832 SNPs (associatedwith melanoma risk according to GWASs) showeda significant difference in the impact of minor alleles on reportergene expression in the UACC903 melanoma cell line. For one of these 30 SNPs (rs398206),which is located in intron 1 of the MX2 gene, the differencewas the largest. It turned out that risk allele A of rs398206significantly enhances the binding of TF YY1 in vitro (inEMSA) and in vivo (according to ChIP-AS-qPCR), therebyupregulating MX2 and thus contributing to the initiation ofmelanoma . Other examples can be foundin refs .By methodically similar Reel-seq and SNP-seq, which arebased on a comparative analysis of the binding of a TF tooligonucleotides containing minor alleles, 521 potential rSNPshave been selected out of 4,316 SNPs correlating with breastcancer according to GWASs as well as403 possible rSNPs out of 903 SNPs associated with prostatecancer . The largest study involving theapproach from this research group was published in 2021. The approach was named SNP-SELEX. Toimplement it, those authors used a library of 383,544 40-bpoligonucleotides containing in the middle all possible allelesof 95,886 SNPs. SNPs were chosen based on either their associationwith type 2 diabetes mellitus in GWASs or localizationwithin a 500-kbp window containing a variant associatedwith this pathology. By means of 270 recombinant TFs, thoseauthors conducted a multiplex analysis of their binding tothe oligonucleotides and identified 11,079 SNPs having anappreciable allele effect on binding to at least one TF.For mass interpretation of the results of GWASs, functionalgenomics data from available databases are also widely used,such as data on genome-wide profiles (ChIP-seq) of TFs\u2019 binding and of histone modifications , on open-chromatin genome-wide profiles (ATACseq), on three-dimensional chromatincontacts , and on locations of enhancerand superenhancer regions as well as data from eQTL analysis.For example, 8,005 SNPs \u2013 either directly associated byGWASs with major depressive disorder or present in the samelinkage group \u2013 have been mapped to ChIP-seq peaks obtainedfrom a brain tissue or cells of neuronal origin by means ofantibodies to 34 various TFs . After that,a search was performed for binding sites of the correspondingTFs in the regions of the SNPs using a database containing7,699 position weight matrices ,and it was revealed that 34 SNPs disrupt the binding sites of15 TFs. A reporter assay confirmed the effect of an allele ongene expression for 29 SNPs. One of them, rs3101339, provedto be located at a potential binding site of TF REST in thepromoter region of the NEGR1 gene, whereas the substitutionof A with C considerably damaged the structure of this site,as evidenced by a decrease in reporter gene expression underthe control of an insert carrying the C allele. The influence ofrs3101339 on NEGR1 gene expression in vivo was confirmedby elimination of an appropriate DNA fragment via CRISPRCas9genomic editing. Since the product of NEGR1 playsan important part in the maintenance of required density ofdendritic spines, its underexpression when A is replaced by Cmay substantially contribute to the development of a depressivestate .Data on genome-wide profiles of active-chromatin histonemarks are also turning out to be very informative for thefunctional interpretation of GWAS results. For example, toanalyze many SNPs correlating with epithelial ovarian cancer,they have been mapped in the region of ChIP-seq peaks forH3K27Ac; these peaks were obtained by the researchers ina study on 26 tissue samples of this type of cancer . Then, using the motifbreakR tool , among the mapped SNPs, 469 SNPs were selected inwhich the nucleotide substitution substantially altered a bindingsite of some TF. The most frequent was the change in thesequence of the binding site of TF REST, for which there aredata on its tumor-suppressive and oncogenic functions . Besides, the use of ChIP-seq datasets on varioushistone modifications from relevant databases in combinationwith data and tools from a database of potential regulatoryvariants (rVarBase) has made it possible todetect in superenhancers 286 and 366 possible rSNPs associatedwith type 2 diabetes mellitus andcoronary heart disease , respectively, thatalter the predicted TFBSs.Modern massive function-based approaches to the identificationof potential rSNPs are mainly based on the registrationof an effect of a nucleotide substitution on some molecularphenotype. This may be (i) determination (in transcriptomes)of a difference in the expression level of individual genesamong homozygotes and heterozygotes for different alleles ofeach SNP , (ii) identification of SNPs showingasymmetry of enrichment within transcriptome data (RNAseq:ASE events) or within epigenomic data , or (iii) determinationof an influence of an allele on reporter gene expressionby MPRA.The term \u201ceQTL\u201d either means that there is a correlationbetween a variant (eVariant) and the expression level ofa certain gene(s) (eGene[s]) or refers directly to an SNP the alleles of which show sucha correlation; the term is used much more frequently in thelatter sense . Transcriptomic data obtainedusingeither microarrays or RNA-seq are suitablefor finding eQTLs. These data are quite sufficient for thedetection of eQTLs located in transcribed regions , whereas the identification of their entire set alsorequires genome sequencing data . In contrast to GWASs, which requirebiological samples from many thousands of individuals , several hundred participants are sufficient foreQTL analysis . Nonetheless, just as in GWASs, in eQTLanalyses, the problem of distinguishing an SNP that is indeedrelevant to the formation of a trait \u2013 among marker variantsdetected through linkage disequilibrium \u2013 is still relevant .The largest-scale project on obtaining transcriptomic dataand identifying eQTLs is international consortium GTEx,within which RNA-seq data on 15,201 postmortem samplesof 49 tissues collected from 838 donors have been collected,allowing to identify 4,278,636 eQTLs associated with changesin the expression of 18,262 and 5,006 genes encoding proteinsand long intergenic noncoding RNAs, respectively .There are other datasets of eQTLs, including those obtainednot on postmortem but on biopsy materials . For example, in a study by Stolzeet al., in an analysis of transcriptomes (RNA-seq) of the aorticendothelium of 157 donors, the investigators identifiedthousands of eQTLs not registered in the GTEx Consortiumdata . Fairfax et al. have employed CD14+monocytes treated in vitrowith either interferon gamma orbacterial cell wall lipopolysaccharide (LPS) . CD14+ monocytes from414 people served as controls there. Through microarrayRNA profiling and genotyping, 609,704 SNPs were examined and 21,516 eQTLs weredetected, 24.6 % of which manifested themselves in controlcells, 21.6 % of which manifested themselves after 2 h oftreatment with LPS, and 25.4 and 28.3 % after 24 h treatmentwith LPS and IFN-\u03b3, respectively. The results of this workpoint to an important role of genomic variants in the natureof transcriptomic response to a drug . Inconclusion, it should be noted that any dataset of transcriptomicdata obtained from hundreds or more individuals can beused to search for eQTLs, as, for example, has been done byus with the help of data from RNAseqanalysis of postmortem brain samples from 96 individuals.At present, quantitative expression trait loci analysis ismainly utilized to identify groups of genes participating intrait formation . Additionally, its results are often used to prioritizeGWAS-identified SNPs for their subsequent rigorous experimentalinvestigation. An example is rs13239597, which islocated in the TNPO3 gene promoter and associated with lupuserythematosus and multiple sclerosis according to GWASs.eQTL analysis of transcriptomes of lymphoblastoid cell linesderived from 373 individuals has not revealed any impact ofrs13239597 on TNPO3 expression but uncovered a significantassociation of the A allele of this SNP with overexpression ofthe IRF5 gene [which is located 118 kbp away ], in agreement with findings of the GTEx Consortium. Next, an analysis of availableHi-C data showed that IRF5 is one of 12 genes that are indirect contact with the rs13239597 region. A computationalanalysis of motifs that potentially change affinity for a TF asa result of a nucleotide substitution hasrevealed four such TFs: EVI1, ERF, GATA1, and TAL1. ByChIP-AS-qPCR, it has been demonstrated that EVI1 bindsmuch better to the rs13239597 region in the case of the A alleleas compared to the C allele . Similarexamples can also be found in refs .The development of next-generation-sequencing-based methodsof transcriptomic analysis (RNA-seq) and epigenomicanalysis has opened upa unique opportunity for quantifying a difference in the enrichmentof two alleles of each heterozygouspolymorphic site of a diploid organism within the respectivedataset . An important feature of these approaches to theidentification of potential rSNPs \u2013 in contrast to eQTL analysis \u2013 is that allele-asymmetric events are recordedfor each individual and the backgrounds are identical. Thisarrangement enables researchers to obtain reliable data whenstudying a very small number of individuals, down to one. An increase in sample size is requiredonly for involving in the analysis a larger number of SNPs thatare in a heterozygous state. For instance, calculations showthat data from 20 individuals theoretically allow to determineASE or ASB events for 65\u201370 % of SNPs that have a populationfrequency of \u22655 % .For this reason, possibilities of pharmacogenetic and pharmacogenomicprojects become much more abundant. Themost striking example of such a project is a simultaneousanalysis of allele-specific effects of 50 substances in primary cultures offive cell types ,each of which is represented by cell samples fromthree individuals . An analysisof the resultant transcriptomic data helped to identify morethan 300 SNPs, an imbalance in the enrichment of the allelesof which within transcriptomes emerged or increasedsignificantly in response to treatment with one or anotherdrug. Via the same approach, inducer -dependent ASE events have been identified in19 immuneresponse genes by an analysis of transcriptomesof blood mononuclear cells from eight individuals as well as 561 ASE events responsive to treatmentof CD4+ T cells withimmobilized anti-CD3/CD28 antibodies . These results open up a new \u2013 unrelated to anya priori hypothesis \u2013 way to elucidate mechanisms of individualsensitivity to drugsThe largest dataset of ASE events at present, containing431 million such events, is derived from data on RNA-seq andwhole-genome sequencing from the GTEx Consortium and is published in a paper by Castel et al. . This dataset can serve as a source formass discovery of rSNPs, for example, in a comparison withdata from GWASs or from eQTL analysis. It is worth notingthat in the absence of whole-genome sequencing data, relevantinformation can be acquired by more sophisticated methodsof bioinformatic search for allele-specific events directly inRNA-seq data .ChIP-seq experiments based on antibodies to various TFsmake it possible to directly register events of allele-asymmetricinteraction of these proteins with their binding sitesin the case of a heterozygous state of SNPs at these sites.In a pioneering work in the laboratory of Claus Wadelius,they analyzed all the then-available data from the ENCODEproject on binding profiles of TFs in cell lines GM12878(B cells), H1-hESC, K562, and SK-N-SH, thereby revealing9,962 SNPs featuring an allelic imbalance in the binding ofa TF (ASB) . By the same approach,3,713 SNPs have been found showing an allelic imbalancein the binding of TFs in HepG2 and HeLa-S3 cells; testing39 of them in a luciferase reporter system has confirmed theeffect of an allele on reporter gene expression for 27 SNPs. A detailed analysis of one of them,rs953413, indicates that the A allele disrupts the binding siteof TF FOXA, resulting in reduced binding of not only thisTF but also of TF HNF4\u03b1 cooperatively interacting with it,thereby ultimately leading to underexpression of ELOVL2and possibly serving as a factor in the pathogenesis of non-alcoholicfatty liver disease .Because allele-asymmetric alterations in profiles of histonemodifications and of open chromatin can reflect SNP-inducedchanges in the binding of TFs , these dataare also widely utilized to find ASB events. For instance, Mauranoet al. have examined 493 openchromatinprofiles (DNase-seq) obtained in various celllines, where 64,599 SNPs with ASB have been found. Theirbioinformatic analysis using position weight matrices for2,203 motifs of TFBSs from different sources indicates thatmost of the identified SNPs can affect the binding of TFsand hence the accessibility of the respective DNA regionsto DNase I . A newer technique fordetecting open chromatin, ATAC-seq, is based on the abilityof a hyperactive mutant of Tn5 transposase to detect openDNA regions in chromatin and isalso used to search for ASB events. In particular, it has beenemployed to identify 53 rSNPs in breast cancer MCF-7 cellsand 125 rSNPs in a line of human mesenchymal stem cells(MSCs); in total, 30 % of the rSNPs found in MCF-7 cells and43 % of those found in MSCs have been identified as eQTLsin GTEx data, indicating their influence on gene expression. Examples of use of data from ChIP-seq(involving antibodies to histone marks) for registering ASBevents can be found in refs .The combination of searches for ASE events and ASBevents can be considered the most productive approach toidentifying rSNPs. For example, in our work , at first, ASB events were identified in ChIP-seqdata from the ENCODE project for histone modificationsH3K27ac, H3K4me1, H3K4me2, H3K4me3, and H3K27me3as well as for 456 TFs and their associated proteins in humancell lines K562, MCF-7, and HCT-116. Then, by means ofRNA-seq data obtained from the same cell lines, SNPs (rSNPs)that are associated with changes in gene expression levels wereidentified. According to GWASs, out of 1,633 rSNPs found inthis way, 27 have shown associations with cancers , and 14, with cognitive disorders . Another 30 rSNPs have been implicated in colorectalcancer with the help of data from the International Cancer GenomeConsortium (ICGC) . Genotypingof patients with colorectal cancer and healthy individuals forsix of these SNPs has revealed an association of rs590352,rs4796672, and rs2072580 with this disease . A correlation with breast cancer has been found forrs2072580 . Later, the same approachhas allowed to identify 14,266 rSNPs during the processingof data obtained in a study by Reyes-Palomares et al. on H3K4me3 histone marker profiling(ChIP-seq) and RNA-seq data on pulmonary-artery epithelialsamples from 19 individuals .Research into the effect of polymorphic-site alleles on reportergene expression via simultaneous transfection of hundredsand thousands of barcoded plasmid constructs into eukaryoticcells with subsequent transcriptome sequencing is also aninformativeapproach to finding rSNPs . The largest-scalestudy based on this approach has been conducted in the laboratoryof Bas van Steensel . Usinga promoterless plasmid and fragmented genomes (fragmentlength 150\u2013500 bp) of four individuals belonging to differentethnic groups, two barcoded libraries were constructedfor each individual, where inserts were expected to play therole of a promoter. At the same time, on the basis of data ontranscription initiation in enhancer regions , those authors expectedto detect not only promoters but also enhancers. The use ofDNA from humans of genetically distant ethnic groups allowedthose investigators to hope for an analysis of the largestpossible number of polymorphic sites that are homozygousfor different alleles in at least two of those people.After transfection of K562 and HepG2 cells with the resultinglibraries, 19 and 14 thousand potential rSNPs, respectively,were found, most of which did not overlap, once again indicatingtissue specificity of the supragenomic (protein) regulatorymachine. The identified SNPs showed significant enrichmentwithin regulatory regions of the genome. In this case, theenrichment (approximately 15-fold) was three times higherin promoter regions than in enhancer regions (approximately5-fold); this outcome is obviously due to the design of thereporter constructs. For several rSNPs, by mass-spectrometricanalysis of proteins interacting with oligonucleotides containingminor alleles, those authors were able to identify TFs thebinding sites of which are altered by a nucleotide substitution.In particular, the A allele of rs623853 was found to disruptthe binding of TFs of the ELF family, whereas the C allele ofrs554591 weakens the binding of ZNF787 while enhancingthe binding of KLF and SP .Programs \u2013 of coordinated switching on, switching off, andchanges of the expression of various genes \u2013 that underlie(1) ontogenesis events, (2) the existence of many types ofdifferentiated cells, and (3) the abilities of cells to respond tovarious factors of the external and internal environment areimplemented by the regulatory part of the genome of multicellularorganisms. The information encoded in the regulatoryregions is converted into a desired pattern of gene expressionprimarily via the binding of TFs to specific sequences in theregulatory regions . Accordingto present-day concepts, the SNPs located in regulatoryregions of genes, affecting binding sites of TFs, and changingthe level of gene expression play a central part in the variationof phenotypic traits, including predisposition/resistanceto multifactorial diseases . In this regard, thereis a strong interest both in functional interpretation of SNPshavingan association with various diseases (primarily accordingto GWAS data) and in the development of massivefunction-based approaches to the discovery of rSNPs. Interpretationof data from GWASs is carried out either at the levelof individual SNPs or for all SNPs collectively by a varietyof functional genomics techniques . Meanwhile, thesame methods of functional genomics are used for personalsearches for rSNPs, but at the same time, it is necessary tosolve the inverse problem: determining a relation between thefound rSNPs and a trait (disease). The most popular solutionto this problem is to compare the obtained data with availableinformation from GWASs . On the other hand, inthis way, usually only 1.5\u20133.0 % of found rSNPs are implicatedin various traits . In this regard, it seems very promising to takeadvantage of results of eQTL analysis, enabling an investigatorto determine an influence of many specific rSNPs on theexpression of fairly large groups of genes, the subsequentanalysis of which by modern functional annotation tools allows to get an idea about a possible affected trait.To sum up, there are two approaches \u2013 based on oppositeprinciples \u2013 to finding SNPs that are important for the developmentof a trait (pathology): on the one hand, starting from dataon an association of an SNP with some trait, and on the otherhand, starting from determination of allele-specific changes atthe molecular level (in the transcriptome or regulome). 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DOI 10.1093/nar/gky1094.Zou J., Hormozdiari F., Jew B., Castel S.E., Lappalainen T., Ernst J.,Sul J.H., Eskin E. Leveraging allelic imbalance to refine fine-mappingfor eQTL studies. PLoS Genet. 2019;15(12):e1008481. DOI10.1371/journal.pgen.1008481."} +{"text": "The corrected Acknowledgments are as follows.B.S. acknowledgesSRA MERGE for creating a stimulating scientificcommunity. B.S. and J.R. acknowledge FORMAS for financial support.C.P. acknowledges the Lund Institute of Technology for postdoc funding.J.R. and A.C.E. further acknowledge financial support via Grant AEROMETII 19ENV08. N.L.P. and J.J.L. acknowledge funding from the Academyof Finland andthe European Research Council (ERC) under the European Union\u2019sHorizon 2020 Research and Innovation program ."} +{"text": "Earthworms are an important ecological group that has a significant impact on soil fauna as well as plant communities. Despite their importance, genetic diversity and phylogeny of earthworms are still insufficiently studied. Most studies on earthworm genetic diversity are currently based on a few mitochondrial and nuclear genes. Mitochondrial genomes are becoming a promising target for phylogeny reconstruction in earthworms. However, most studies on earthworm mitochondrial genomes were made on West European and East Asian species, with much less sampling from other regions. In this study, we performed sequencing, assembly, and analysis of the mitochondrial genome of Dendrobaena tellermanica Perel, 1966 from the Northern Caucasus. This species was earlier included into D. schmidti , a polytypic species with many subspecies. The genome was assembled as a single contig 15,298 bp long which contained a typical gene set: 13 protein-coding genes , 12S and 16S ribosomal RNA genes, and 22 tRNA genes. All genes were located on one DNA strand. The assembled part of the control region, located between the tRNA-Arg and tRNA-His genes, was 727 bp long. The control region contained multiple hairpins, as well as tandem repeats of the AACGCTT monomer. Phylogenetic analysis based on the complete mitochondrial genomes indicated that the genus Dendrobaena occupied the basal position within Lumbricidae. D. tellermanica was a rather distant relative of the cosmopolitan D. octaedra, suggesting high genetic diversity in this genus. D. schmidti turned out to be paraphyletic with respect to D. tellermanica. Since D. schmidti is known to contain very high genetic diversity, these results may indicate that it may be split into several species. Earthworms are an important ecological group that accountsfor the highest biomass among the soil fauna in many habitats. Its representatives process plant detritusto soil humus and return organic matter to the global cycles. Earthworms also form soil structure,which has high impact on both soil fauna composition andvegetation . Therefore, this group definesecosystem productivity in many respects.Genetic diversity and phylogeny of earthworms remaininsufficiently studied . Currently, mostworks on earthworm genetic diversity are based on singlemitochondrial and nuclear genes . Construction of multigene nucleardatasetsis impededby frequent polyploidy characteristic forthis group , which makes it hard to detectsuitable orthologs and amplify them by PCR.Mitochondrial genomes are thus a promising tool forreconstruction of phylogenetic relationships in earthworms.A lot of mitochondrial genomes were sequenced and publishedin recent years , and studieson phylogenetic relationships of certain groups were alsoconducted . However,almost all of these studies were made on species fromWest Europe and East Asia, with almost no representativesof other regions.In this study, we performed sequencing, assembly, andanalysis of the mitochondrial genome of Dendrobaena tellermanicaPerel, 1966. This species was earlier included intoD. schmidti , a polytypic species that wasconsidered to contain multiple subspecies . D. tellermanica was believed to be a parthenogeneticform of D. schmidti . T.S. Vsevolodova-Perel (2003) demonstrated that many populations ofD. tellermanica are amphimictic and so isolated itinto a separate species. D. tellermanica differs from D. schmidtiby the lack of pigmentation, different position of the clitellumand the form of tuberculae pubertatis .Currently, there is only one complete mitochondrial genomeof the genus Dendrobaena in GenBank belonging to thecosmopolitan D. octaedra . The mitochondrialgenome of D. tellermanica will be the first sequencedmitochondrial genome of a Caucasian earthworm and will beimportant for studying the phylogeny of lumbricidsSpecimens of D. tellermanica were collected in the Karachay-Cherkess Republic .Worms were fixed in ethanol. Morphological identificationwas performed according to the key of T.S. Vsevolodova-Perel (1997).DNA was extracted using the standard phenol-chloroformmethod and sonicated on Covaris M220 to the target fragmentlength of 350 bp. The fragments were purified by 1.2 volumeof AMPureXP and quantified usingfluorometry on a Qubit device. Genomic libraries were obtainedfrom 100 ng of DNA using Roche KAPA Hyper Prepaccording to the manufacturer\u2019s protocol using KAPA UDIAdapter double barcodes. Quality and molarity of the obtainedgenomic library was assessed on a BA2100 bioanalyzerusingthe Agilent DNA High Sensitivity Kit and sequencedon an Illumina NextSeq550 with the Mid Output Kit v. 2.5(300 Cycles) for 2\u00d7150 bp paired readsThe obtained data were processed by TrimmomaticPE with the ILLUMINACLIP:TruSeq3-SE:2:30:10 SLIDINGWINDOW:4:15 MINLEN:36 options.SPAdes v. 3.14.1 was used for contig assembly with the --isolate option. The assembled contigswere aligned with mitochondrial earthworm genomes fromthe NCBI database with blastn (https://blast.ncbi.nlm.nih.gov)in order to search for mitochondrial sequences.Preliminary annotation was done by MITOS 2 with subsequent manual comparison with annotatedearthworm genomes. The mitochondrial genome of D. tellermanicawas deposited in GenBank under accession numberON960857. Map of the genome was constructed using Benchling(https://www.benchling.com/).Secondary structures of tRNAs were visualized usingMITOS 2 ; of the control region, usingRNAfold Web Server (http://rna.tbi.univie.ac.at/cgi-bin/RNAWebSuite/RNAfold.cgi) and forna (http://rna.tbi.univie.ac.at/forna/forna.html) . Search for tandemrepeats was done by Tandem Repeats Finder . For phylogenetic reconstructions, mitochondrial genomeswere aligned with Clustal Omega ; control regions were not includedinto the alignments. Ambiguously aligned regions were removedwith gblocks 0.91b . Earthwormmitochondrial genomes and sequences of the COX1 gene ofrepresentatives of the Dendrobaena genus were extractedfrom GenBank. Phylogenetic trees were built using the MaximumLikelihood approach in RAxML v. 8.2.12 (Stamatakis 2014) with the GTRCAT substitution model;1000 bootstrap replicates were performed.We obtained 4.2 million paired reads for theD. tellermanica genomic library; 3.4 mil-lion remained after processing. Mediancoverage of genome contigs longer than500 bp was estimated at 6 (average \u2013 20),median coverage for the mitochondrialcontig was 20 (average \u2013 30).The assembled mitochondrial contigwas 15,298 bp long and contained the typicalset of genes: 13 protein-coding genes, 12S and 16S ribosomalRNA genes, and 22 tRNA genes. All geneswere located on one DNA strand .AT- contentwas 65.3 %. The leading strandcontained 31.1 % \u0410, 34.2 % \u0422, 13.9 % G,and 20.8 % C. The ND4 and ND4L genesoverlapped by 7 bp. ATG was the only startcodon used. Three protein coding genes had an abbreviatedstop codon. Transport RNA genes were 60to 69 bp long, their predicted structures areshown on Fig. 2.The region between the tRNA-Arg andtRNA-His genes is known as the controlregion. A total of 727 bp were assignedto it. The control region could not be assembled,so the final sequence containeda gap. Its \u0410\u0422-content (63.5 %) was closeto the genome average, and its sequencecontained multiple hairpins .It also included 11 tandem repeats of theAACGCTT monomer.Organization of mitochondrial genomein earthwormsFor a long time, the study of J.L. Booreand W.M. Brown (1995) on Lumbricusterrestriswas the only description of anearthworm mitochondrial genome. It was14,998 bp long and contained a set ofgenes usual for animal mitochondria. Thehallmark of earthworm mitochondrial genomes,as well of Annelida as a whole, withfew exceptions, is that all genes are locatedon a single strand .All mitochondrial genes in earthworms arepresumably expressed as a single transcript. In this case, anyinversions and most of the translocationswill be non-viable, which leads to fixed gene positions in the genome. Indeed,mitochondrial gene order in annelids is highly conserved, and all Clitellata haveidentical gene order. We also failed to find any deviations from this rule.While mtDNA gene order in earthworms is conserved, its sequence is highlyvariable, which is especially pronounced for the control region . The control region acts as the replication origin, promotor, andthe regulatory region for the mitochondrial gene expression .Organization of the control region varies in different earthworm taxa. Amongthe representatives of Glossoscolecidae and Megascolecidae they are short,usually less than 500 bp , while in two species of Drawida(Moniligastridae) these sequences were completely absent . In Lumbricidae, the length of the control region varies from 400 bp inL. terrestristo 2000 bp in Eisenia fetida. For many species, control regionscould not be amplified or even recovered using NGSmethods . Here, we also failed to amplify the lacking partof the control region of D. tellermanica. This could be caused by its length orcomplex secondary structure: Fig. 2 demonstrates that almost all of the controlregion forms hairpins.The phylogeny of earthworms based on mitochondrial genomesand the position of D. tellermanicaPhylogenetic analysis based on complete mitochondrial genomes suggests that Moniligastridae is distantly related to other earthworm families.Glossoscolecidae, represented here by a single species Pontoscolex corethrurus,occupied the basal position within the order Crassiclitellata. Megascolecidaeand Lumbricidae, which were the most densely sampled, turned out as sistergroups.Within the family Lumbricidae, which includes D. tellermanica,the genus Dendrobaena was the sister group toall other genera of the family. There are only two knownmitochondrial sequences for the genus Dendrobaena, thecosmopolitan D. octaedra and D. tellermanica obtained inthis study. Expectedly, D. tellermanica forms a clade withD. octaedra, but they are rather distantly related.We can conclude that this work is a first step in the studyof the basal branches of Lumbricidae. Representatives ofthe genus Dendrobaena from the Caucasus are particularlyinteresting in this respect, because they account for a largepart of its species diversity.Earlier we performed a genetic analysis of morphologicalforms of D. schmidti , demonstratingthat it represents at least two separate species. On thephylogenetic tree constructed using the COX1 gene ,D. tellermanica was inside one of the branches of D. schmidti.We should note that single mitochondrial genes, includingCOX1, are unsuitable for phylogenetic reconstruction on thefamily level , since they demonstrate poor resolution of the relationshipsbetween species and do not support the monophylyof most genera. COX1 is however of much use in the searchfor closely related species or genetic lineages. Moreover, thereare thousands of COX1 sequences in the public databasesand only a few mitochondrial genomes; e. g., mtDNA ofD. schmidtihas not been sequenced yet. Therefore, the treeon Fig. 4 is given only to demonstrate the close relationshipof D. tellermanica and D. schmidti.The obtained preliminary results indicate that D. tellermanicacould be treated as a subspecies of D. schmidti, as was believedearlier, or split D. schmidti into several species. 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DOI 10.3390/d14090714."} +{"text": "Journal of Applied Research in Memory and Cognition, 2022, Vol. 11, No. 1, pp. 120\u2013134, https://doi.org/10.1016/j.jarmac.2021.07.010), should have been published under the terms of the Creative Commons Attribution License (CC BY 3.0). Therefore, the article was amended to list the authors as copyright holders, and information about the terms of the CC BY 3.0 was added to the author note. In addition, the article is now open access. The online version of this article has been corrected.The article \u201cFace Identification in the Laboratory and in Virtual Worlds,\u201d by Markus Bindemann, Matthew C. Fysh, Iliyana V. Trifonova, John Allen, Cade McCall, and A. Mike Burton ("} +{"text": "Sergei Krivonogov was not included as an author in the original publication . The corAuthor Contributions: Conceptualization S.K., A.S. and A.M.; methodology, A.M. and A.S.; software, D.Z.; validation, D.Z., A.M. and A.S.; formal analysis, A.S.; investigation, A.M. and D.Z.; resources, S.K. and A.M.; data curation, D.Z.; writing\u2014original draft preparation, D.Z., A.S. and A.M.; writing\u2014review and editing, S.K., D.Z. and A.S.; visualization, D.Z. and A.M.; supervision, S.K. and A.S.; project administration, S.K.; funding acquisition, S.K. All authors have read and agreed to the published version of the manuscript.In the published publication , there wIn the original publication , the funFunding: This research was funded by RFBR-NSFC grant 21-55-53037 and state assignments from The Ministry of Science and Higher Education of the Russian Federation (#AAAA-A16-11611091001 and 0330-2016-0011) and performed using the equipment of the Core Facilities Center of IPCE RAS (CKP FMI IPCE RAS) and the Analytical Center for Multi-element and Isotope Studies of the V.S. Sobolev Institute of Geology and Mineralogy (Novosibirsk). Work was done on state assignment of V.S. Sobolev Institute of Geology and Mineralogy Siberian Branch Russian Academy of Sciences, Project N 122041400193-7.We changed the acknowledgements accordingly:Acknowledgments: The authors are grateful to Rysbek Satylkanov, of the Tien Shan High Mountain Scientific Centre National Academy of Sciences of the Kyrgyz Republic, for hosting our field work. We thank Nadezhda Popova and Denis Sobolev for their laboratory assistance.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Nature Communications 10.1038/s41467-023-37470-4, published online 22 April 2023Correction to: In this article the author name David J. Jackson was incorrectly written as J. David Jackson, the author name Michael R. Edwards was incorrectly written as R. Michael Edwards, the author name Sebastian L. Johnston was incorrectly written as L. Sebastian Johnston and the author name Cezmi A. Akdis was incorrectly written as A. Cezmi Akdis. The original article has been corrected."} +{"text": "Salvia genus comprises about 1000 species endowed with medicinal, aromatic, cosmetic, and ornamental applications. Even though the genus is one of the most-studied taxa of the Lamiaceae family, data on the chemical composition and biological properties of certain locally used Salvia species are still scarce. The present work aimed to evaluate the phytochemical profile and antimicrobial, antioxidant, and cytotoxic potential of ten Salvia species that grow in Eastern Europe . LC-HRMS/MS metabolite profiling allowed for the annotation of 15 phenolic and organic acids, 18 flavonoids, 19 diterpenes, 5 sesterpenes, and 2 triterpenes. Multivariate analysis revealed that S. austriaca, S. nutans, and S. officinalis formed individual clusters, whereas the remaining species had a similar composition. S. officinalis showed the highest activity against Staphylococcus aureus and Streptococcus pneumoniae (MIC = 0.625 mg/mL). As evaluated in DPPH, ABTS, and FRAP assays, S. officinalis was one of the most potent radical scavenging and metal-reducing agents , followed by S. verticillata, S. sclarea, S. kopetdaghensis, S. aethiopis, and S. tesquicola. Pearson correlation analysis revealed strong correlations with rosmarinic acid, luteolin-O-glucuronide, and hydroxybenzoic acid. When the cytotoxic activity was evaluated in human breast carcinoma MCF-7 and MDA-MB-231 cells, no significant reduction in cell viability was observed over the concentrations ranging from 25 and 100 \u03bcg/mL. The results confirm the potential use of understudied Salvia species as promising sources of antioxidant compounds for developing novel pharmaceutical, nutraceutical, or cosmeceutical products. The Salvia is one of the largest genera of the Lamiaceae family, consisting of about 1000 species. It includes medicinal, aromatic, culinary, and ornamental plants with many pharmaceutical, food, and cosmetic applications. Although Salvia plants are distributed worldwide, they are predominantly found in temperate and tropical areas DPPH scavenging activity (%) = 100 \u00d7 ABTS scavenging activity (%) = 100 \u00d7 \u00d7 100% cell viability = [Absorbance.The cell viability was evaluated using the MTT assay . Brieflyp < 0.05 was considered statistically significant. After Pareto scaling, the phytochemical data (peak areas from the base chromatograms) were imported into SPSS 20.0 software and used to perform principal component analysis, hierarchical cluster analysis, and Pearson correlation analysis. For antioxidant tests, the EC50 values were calculated by linear interpolation between values above and below 50% activity. In the FRAP assay, the EC50 value represents the concentration of extract/positive control that leads to an absorbance of 0.5.Data are presented as mean \u00b1 standard deviation of the respective number of replicates. One-way analysis of variance with Tukey\u2019s post hoc test was conducted; S. officinalis (126.91 mg GAE/g extract), followed by S. sclarea (110.90 mg GAE/g extract), S. kopetdaghensis (107.63 mg GAE/g extract), and S. verticillata (107.62 mg GAE/g extract). S. nutans and S. austriaca had the lowest contents of phenolic compounds among the investigated Salvia species . Our results align with the findings of other studies on Salvia phenolics. S. verticillata, S. nemorosa, and S. aethiopis from Turkey contained 167.1, 63.9, and 82.1 mg GAE/g extract, respectively [S. verticillata from Serbia and S. sclarea from Iran contained outstanding amounts of total polyphenols [S. officinalis from Romania. Hanganu et al. [Salvia species from spontaneous Moldavian flora . The provenience of plant material, the geographical and pedo-climatic factors that influence the growing and harvesting time, and the mode of results expression could explain the different outcomes. In our study, the plants were collected from field crops, while in the mentioned research, the plants were harvested from spontaneous flora. Mocan et al. [S. transsylvanica from Romania and pointed out that cultivated plants could produce higher levels of polyphenols than wild plants. In addition, abiotic factors such as rainfall, temperature, and cloud cover play significant roles in sage phenolics biosynthesis [The values of TPC are shown in ectively . Furtherctively) ,21. A prctively) showed Tn et al. reportedynthesis . Salvia species. Previously, the comprehensive phytochemical characterization of S. officinalis revealed the presence of more than 40 compounds, such as phenolic acids, flavonoids, diterpenes, and triterpenes [S. miltiorrhiza Bunge was profiled using LC-MS, evidencing two main structural groups, namely, phenolic acids and diterpenes (tanshinones) [O-glucoside, apigenin-7-O-glucoside, cirsimaritin, eupatorin), phenolic acids , and diterpenes in 50 Salvia species collected from different regions of Iran, including S. indica L., S. grossheimii Sosn., S nemorosa, S. palaestina Benth., S. spinosa L., S. syriaca L., and S. verticillata. Zengin et al. [Salvia species endemic to Turkey, namely, S. blepharochlaena Hedge and Hub.-Mor., S. euphratica var. leiocalycina (Rech.f.) Hedge, and S. verticillata subsp. amasiaca (Freyn and Bornm.) Bornm. Salvia species from Pakistan [S. veneris Hedge, S. poculata, S. eriophora Boiss. and Kotschy, S. ceratophylla L., S. sclarea, S. absconditiflora Greuter and Burdet) [S. pomifera L., S. fruticosa Mill.) [S. przewalskii Maxim., S. cadmica Boiss., S. yangii B.T. Drew, S. abrotanoides Kar.) [LC-MS platforms are extensively used to perform metabolite profiling, not only of common sage species but also of less-investigated or endemic terpenes . S. milthinones) ,26. Shojhinones) documentn et al. reportedebeiana) , Turkey Burdet) ,31,32,33a Mill.) ,35, and es Kar.) ,36,37 weSalvia species allowed for the annotation of 73 compounds belonging to 8 phytochemical classes. Total identification was performed by matching the spectro-chromatographic data with those obtained by standard injection, whereas partial identification was conducted by comparing the acquired data with those from databases , followed by S. sclarea (55 compounds) and S. verticillata (52 compounds). Next, 48 compounds were assigned in S. austriaca and S. kopetdaghensis, 46 compounds in S. nutans, 44 compounds in S. tesquicola and S. pratensis, 41 compounds in S. officinalis, and 39 compounds in S. nemorosa. To our knowledge, the LC-HRMS/MS-based phytochemical profiling of S. nutans and S. kopetdaghensis was performed herein for the first time, whereas a few studies have profiled S. sclarea [S. aethiopis [S. verticillata [S. nemorosa [S. pratensis [S. austriaca [In the current study, the LC-HRMS/MS-based metabolite profiling of the ten KNApSACK ) or rele species ,41,42,43 sclarea , S. aethicillata ,45, S. nnemorosa , S. pratratensis , and S. 5 and 6), hydroxycinnamic acids , and hydroxycinnamic acid oligomers . Dihydroxybenzoic acid (5) was present only in S. nemorosa, whereas feruloylmalic acid (18) was identified only in S. aethiopis. Furthermore, salvianolic acid H was annotated only in S. pratensis, while caffeoylthreonic acid (9) was distributed specifically in S nemorosa and S. pratensis. Caffeic acid-O-hexoside (14), a phenolic glycoside, was characteristic of S. nutans and S. officinalis. Interestingly, caffeic acid (8) and rosmarinic acid (23) were ubiquitously found in all species, while hydroxybenzoic acid (6) was absent only in S. austriaca. In a previous study [S. fruticosa. Salvianolic acid B, salvianolic acid K, and chlorogenic, caffeic, ferulic, coumaric, and rosmarinic acids were documented in S. officinalis [O-hexoside, protocatechuic acid, coutaric acid, coumaric acid) in S. blepharochlaena, S. euphratica var. leiocalycina, and S. verticillata subsp. amasiaca. Thirteen phenolic acids were labeled in the ten sage species, classified as hydroxybenzoic acids , flavones aglycons , flavone glycosides , and flavonol glycosides . Apigenin-O-pentoside-O-hexoside (10), chrysoeriol-O-acetylglucuronides I (30), and II (33) were observed only in S. nutans. Luteolin-O-hexoside-O-glucuronide (11) was characteristic of S. tesquicola, whereas quercetin-O-hexoside (13) was found only in S. officinalis. Interestingly, luteolin-7-O-glucoside (17) and luteolin-O-glucuronide I (20) were retrieved in all ten sage species. Luteolin-O-acetylglucuronide (28) was found only in S. nutans and S. verticillata, while apigenin was distributed specifically in S. sclarea and S. austriaca. Luteolin-O-hexoside-O-rhamnoside (15) was present in S. tesquicola, S. nutans, and S. officinalis, whereas apigenin-7-O-glucoside (21) was specific to S. sclarea, S. nemora, and S. austriaca. Genkwanin (48), a methoxylated flavone, was distributed in S. sclarea, S. pratensis, and S. austriaca. Previously, flavonoids with similar structures were found in sage species [A series of 18 flavonoids was next labeled as flavanol aglycons or carnosol . S. officinalis was the only species that contained rosmanol II (42), methoxycarnosol (54), acetylhorminone II (64), and rosmaridiphenol (65). Salvipiliferol (58), hydroxysalviol (62), and salviol (70) were characteristic of S. nemorosa. Acetylhorminone I (51) was shown only in S. verticillata, whereas dihydroxycarnosic acid (55) was specifically found in S. tesquicola and S. kopetdaghensis. S. sclarea and S. tesquicola were the only species containing hydroxcarnosic acid I (37), whereas carnosol (59) was present only in S. officinalis and S. kopetdaghensis. Diterpenes are widely reported in the Salvia genus. For instance, Koutsoulas et al. [S. fruticosa and two diterpenes in S. pomifera. Rosmanol, rosmaridiphenol, epirosmanol, epiisorosmanol, and methoxycarnosol were found in S. veneris [S. officinalis [With 19 congeners, diterpenes were the largest phytochemical class in s et al. retrieve veneris , whereasicinalis . 43), C\u2019 (46), and A (50) in S. nutans; and salvimirzacolides I (44) and II (57) in S. aethiopis. Previously, lachnocalyxolides were identified in S. lachnocalyx Hedge [S. mirzayanii Rech. f. and Esfand. [72) and ursolic acid (73) were labeled as triterpenes in almost all Salvia species. Oleanolic acid (72) was absent in S. sclarea, S. aethiopis, S. officinalis, and S. kopetdaghensis, whereas ursolic acid (73) was not present in S. sclarea, S. aethiopis, S. austriaca, and S. kopetdaghensis. These triterpenes were previously reported in S. pomifera. and S. fruticosa [2), quinic acid (3), and one sugar derivative, sucrose (1), were identified as non-specific metabolites in the polar region of the chromatograms Esfand. . Nonetheruticosa . Further23) was the most predominant compound in S. sclarea, S. tesquicola, S. aethiopis, S. verticillata, S. officinalis, S. nemorosa, S. pratensis, and S. kopetdaghensis. Gallocatechin (22) was dominant in S. nutans, while salvianolic acid B (35) was abundant in S. kopetdaghensis. Luteolin-7-O-glucoside (15) was the major constituent in S. aethiopis, S. nemorosa, and S. austriaca. Caffeic acid (8) was found in relatively high levels in S. aethiopis and S. nutans. Luteolin (31), cirsimaritin (41), and apigenin (36) were significant in S. sclarea and S. austriaca. Carnosol (59), methylcarnosic acid (68), and rosmanol (45) were predominant in S. officinalis, whereas carnosic acid (52) and hydroxycarnosic acid (47) were found in high amounts in S. tesquicola. In an attempt to point out more objectively the chemotaxonomic differences between the ten sage species, a multivariate analytical approach based on principal component analysis and hierarchical cluster analysis was subsequently applied. The semi-quantitative data were used as input information. As shown in the component plot , Gram\u2212 bacteria (E. coli and P. aeruginosa), and yeasts . The results when tested against S. aureus and S. pneumoniae. Furthermore, Salvia sclarea behaved more actively on the same bacteria (MIC = 1.25 mg/mL). Among the analyzed Salvia species, S. nemorosa and S. pratensis were the most active against Candida albicans (MIC = 1.25 mg/mL).Screening plant sources to determine their antimicrobial properties is an important strategy to find new therapeutic anti-infective solutions and combat the multidrug-resistance phenomenon. It is estimated that about 75% of the pharmaceuticals used in anti-infective therapy are obtained from natural sources . The ext results showed tSalvia species. For instance, extracts from S. pratensis showed MIC values between 5 and 20 mg/mL against S. aureus, P. aeruginosa, E. coli, and C. albicans [S. verticillata displayed MIC values between 1.25 and 20 mg/mL against a panel of eight bacterial and eight fungal strains [S. aethiopis, S. nemorosa, and S. sclarea also showed MIC values between 1.25 and 20 mg/mL against E. coli, K. pneumoniae, S. typhi, B. subtilis, S. epidermidis, and S. aureus [S. officinalis exhibited MIC values between 0.01 and 0.18 mg/mL against E. coli, P. aeruginosa, S. typhimurium, L. monocytogenes, E. cloacae, M. flavus, B. cereus, and S. aureus. Gram-positive bacteria are more susceptible to Salvia extracts. The resistance of Gram-negative bacteria can be related to their multi-layered highly complex cell structure consisting of inner and outer membranes [Salvia species are capable of inhibiting the growth of different pathogens affecting multiple targets of microbial cells. Flavonoids, such as apigenin, luteolin, and quercetin derivatives, may cause cell-membrane damage, and inhibition of nucleic-acid synthesis and of the bacterial respiratory chain [Previous literature reports revealed comparable antimicrobial properties of strains . S. aeth. aureus . Mocan e. aureus showed tembranes . The outembranes . Althougry chain . Antimicry chain ,53. Sagery chain . Salvia species was assessed in three in vitro tests, namely, DPPH, ABTS, and FRAP. The results, presented as EC50 values . On the contrary, S. nutans and S. austriaca showed the weakest anti-radical activity. A similar trend was found in the ABTS assay when the EC50 values varied from 8.13 and 59.16 \u00b5g/mL. The following decreasing activity order can be concluded: S. officinalis > S. verticilata > S. kopetdaghensis > S. pratensis > S. nemorasa > S. aethiopis ~ S. sclarea > S. tesquicola >> S. nutans > S. austriaca. Lastly, the reducing power revealed that S. kopetdaghensis (EC50 = 19.75 \u00b5g/mL), S. verticillata (EC50 = 19.75 \u00b5g/mL), and S. officinalis (EC50 = 19.75 \u00b5g/mL) were the most active samples. Reactive oxygen species and oxidative stress are involved in many pathologies . The antioxidant abilities of plant products may be an important strategy to improve cell responses to injuries, counteract noxious and pathogenic stimuli, and preserve cell health status. The antioxidant capacity of the ten Moldavian 0 values , show th50 values between 80.09 and 158.76 \u00b5g/mL in DPPH and 1.39 and 8.04 mol Trolox equivalents (TE)/mg in FRAP were reported for the extracts obtained from S. aethiopis, S. austriaca, S. sclarea, S. nutans, S. verticillata, and S. nemorosa [S. officinalis, S. sclarea, S. pratensis, S. austriaca, S. nemorosa, and S. verticillata displayed potent DPPH radical scavenging (53.44\u2013189.94 \u03bcg TE/mL) and FRAP (1.19\u20135.89 \u03bcmol TE/100 mL) activities [S. verticillata showed good antioxidant activity, as assessed in DPPH (EC50 = 33.04 \u03bcg/mL), ABTS (EC50 = 67.01 \u03bcg/mL), and NO (EC50 = 73.12 \u03bcg/mL) radical scavenging assays [50 = 19.84 \u03bcg/mL), reducing power , and Trolox equivalent antioxidant capacity (13.30 mg TE/g) for S. verticillata. Similarly, the aerial parts extract of S. pratensis revealed EC50 values of 50.17 and 90.65 \u03bcg/mL in DPPH and ABTS radical scavenging tests, respectively [S. aethiopis in DPPH, FRAP, and cupric-ion-reducing antioxidant (CUPRAC) assays. Extracts from S. sclarea were shown to scavenge DPPH (85.08 mg TE/g) and ABTS (33 mg TE/g) radicals, reduce ferric (77.06 mg TE/g) and cupric (144.75 mg TE/g) ions, and chelate ferrous ions (37.27 mg EDTAE/g) [Salvia species are also documented in the literature [Our results are comparable with those from the existing literature. For instance, CEnemorosa . Similartivities . S. vertg assays . In addig assays reportedectively . Tohma eEDTAE/g) . The antH EC50 = .04 \u03bcg/mLterature ,49,57,58O-glucuronide correlated well with the DPPH-radical-scavenging, ABTS-radical-scavenging, and metal-reducing activity. Rosmarinic acid and luteolin derivatives are particularly known to exert potent antioxidant effects, as revealed by numerous studies [In an attempt to correlate the observed antioxidant activity with the studies ,60. Salvia species are a rich reservoir of many compounds with multiple bioactivities and have attracted great interest in screening cytotoxic agents. This section presents the influence of five selected sage species on the viability of human breast carcinoma MCF-7 and MDA-MB-231 cell lines. The MCF-7 cell line retains estrogen and progesterone receptors and is highly responsive to chemotherapy. MDA-MB-231 is a highly invasive and aggressive triple-negative breast cancer cell line [Salvia species were chosen according to their use in Moldavian traditional medicine for different kinds of tumors [Salvia species and their metabolites. Plant-derived products are highly valuable resources for developing chemopreventive and anticancer agents. Over 60% of anticancer drugs are obtained from natural products . Salvia ell line ,63. The f tumors . Breast f tumors , is alsoSalvia extracts. A similar effect was reported by Mocan et al. [S. glutinosa and S. transsylvanica at intermediary doses on MCF-7 and HepG2 cells. Furthermore, some previous studies revealed low cytotoxicity of the Salvia genus. For example, extracts derived from S. verticillata showed no viability reduction in epidermoid carcinoma A431, liver cancer HepG2, and colon carcinoma LoVo cells at concentrations of 5 to 50 \u03bcg/mL [S. pratensis, with IC50 values for aerial part extracts >200 \u03bcg/mL in A431 cells [S. verticillata subsp. amasiaca, S. euphratica var. leiocalycina, and S. blepharochlaena in human alveolar lung epithelial carcinoma A549 and human breast adenocarcinoma MCF-7 cells. The cytotoxicity of eleven Salvia species was tested in MCF-7, acute promyelocytic leukemia HL60, and chronic myelogenous leukemia K562 cells, revealing IC50 values generally higher than 50 \u03bcg/mL [S. glutinosa and S. transsylvanica against HepG2, A549, and MCF-7 cell lines with IC50 values greater than 100 \u03bcg/mL. Furthermore, Nicolescu et al. [50 values between 131.68 and 293.79 \u03bcg/mL for various extracts of S. glutinosa in MCF-7, HepG2, non-small cell lung carcinoma NCI H460, and cervical carcinoma HeLa cells. In our study, no sample showed a significant reduction in cell viability over the concentration domain ranging from 25 to 100 \u03bcg/mL . On the n et al. in the c50 \u03bcg/mL . Similar31 cells confirme50 \u03bcg/mL showed au et al. evidenceS. hispanica, S. pilifera, S. macrosiphon), prostate , colon (S. fruticosa), and breast cancer [Although many studies have revealed good cytotoxic potential of certain sage species in lung (roleuca) ,65,66 thSalvia species from ex situ crop cultures . To the best of our knowledge, this is the first study on Moldavian sage plants from field crops regarding non-volatile chemical composition and biological activity. Moreover, data about LC-HRMS/MS-based phytochemical profiling of S. kopetdaghensis and S. nutans are reported herein for the first time. S. officinalis, S. sclarea, S. kopetdaghensis, and S. verticillata are valuable sources of polyphenols. LC-HRMS/MS metabolite profiling indicated a rich composition of sage plants, including eight chemical classes . S. aethiopis presented the most complex profile. Hydroxybenzoic acids, hydroxycinnamic acids, and their oligomers were identified in sage species having a specific distribution. Caffeic and rosmarinic acids were ubiquitously distributed in all Salvia species. Salvianolic acids were primarily found in S. officinalis, S. tesquicola, S. nemorosa, S. kopetdaghensis, and S. pratensis. Luteolin, apigenin, and quercetin derivatives were the main flavonoids identified, but the composition varied between the tested sages. Luteolin derivatives were present in all species, with luteolin-7-O-glucuronide being the most common flavonoid. Rosmanol and carnosol derivatives were the main diterpenes in the investigated Moldavian sage plants. Among the triterpenes, oleanolic and ursolic acids were present in S. nemorosa, S. nutans, S. verticillata, and S. tesquicola. Multivariate analysis showed that Moldavian S. officinalis, S. austriaca, and S. nutans formed individual clusters. All analyzed sages scavenged free radicals and acted as reducing agents, with S. officinalis, S. verticillata, and S. kopetdaghensis being the most effective antioxidants. The highest antimicrobial activity was found for S. officinalis. The tested Salvia species did not show cytotoxic properties on breast cancer cell lines (MCF-7 and MDA-MB-231) On the contrary, the extracts seemed to show proliferative activity on tested cell lines. In this regard, for a substantiated statement, it is necessary to investigate a broader range of doses and variations of the exposure period.Our study provides data on the chemical profile and potential bioactivities of ten Moldavian Salvia species, providing evidence for future studies that can lead to developing sage-based health-promoting agents in oxidative stress-related disturbances and redox medicine.Our research contributes to knowledge about the chemistry and biological potential of understudied Moldavian"} +{"text": "Lately, comparative transcriptome analysis has demonstrated that bovine horns and cervid antlers most likely share the same cellular origin, namely from neural crest stem cells [16].Previous studies have demonstrated that sheep horn formation is initiated during the embryonic period .RNA sequencing (RNA-seq) is a high-throughput technology that provides a comprehensive view of the entire transcriptome, which contributes to a better understanding of embryonic development and the role of genes .The shape of sheep horn buds is similar to that of cattle horn buds [20].The featureCounts program in Subread (v2.0.3) was used to calculate the gene expression of horn buds and skin tissues [21].The package DESeq2 v1.36.0 of R software [22] was used to examine DEGs in horn buds and skin tissues.https://biit.cs.ut.ee/gprofiler/gost (accessed on 15 September 2022)) and KEGG Mapper (https://www.genome.jp/kegg/mapper/color.html (accessed on 15 September 2022)) tools.This was carried out on the g: Profiler and compared them with the DEGs identified in this study; these sets included the horn-related genes and proteins of sheep, goats, and cattle horns identified in previous studies .The embryonic period is crucial for the differentiation and formation of sheep horn [17].In this study, the histological results showed that the horn buds were significantly different from the forehead skin, having a thicker epidermis and more layers of epithelial cells, both of which findings have been previously reported . However, the vacuolated keratinocytes previously found reported in the horn buds of cow fetuses were not observed in the present study [20]. Meanwhile, in a previous study of Merino sheep, the vacuolated keratinocytes were not found in the development of horn buds from 75 days of gestation to adulthood [17].FOXL2 gene is involved in horn bud differentiation [36], and is associated with horn growth in goats [33]. Previous proteomic analysis has suggested that TNN is associated with the formation of horn deformity in sheep [27].It is also related to horn size, length, and shape in sheep , indicating that it plays a vital role in horn development during the embryonic period. The Venn diagram of DEGs and horn-related genes. A: DEGs; B: Horn-associated genes in transcriptome studies by Wang, Y. et al., Pannetier, M. et al., and Boulanger, L. et al.; C: Horn-associated genes in proteome studies by He, X. et al.; D: Horn-associated genes in genome studies by Li, Y. et al., Montgomery, G.W. et al., Kijas, J.W. et al., Wiedemar, N. et al., Luhken, G. et al., He, X. et al., Ren, X. et al., Pailhoux, E. et al., and Medugorac, I. et al.Protein Sci.2022, 31, 47\u201353. https://doi.org/10.1002/pro.4172.23. Kanehisa, M.; Sato, Y.; Kawashima, M. KEGG mapping tools for uncovering hidden features in biological data. Nucleic Acids Res.2023, 51, D587\u2013D592. https://doi.org/10.1093/nar/gkac963.24. Kanehisa, M.; Furumichi, M.; Sato, Y.; Kawashima, M.; Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Bioinformatics2014, 30, 923\u2013930. https://doi.org/10.1093/bioinformatics/btt656.25. Liao, Y.; Smyth, G.K.; Shi, W. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Genome Biol.2014, 15, 1\u201321. https://doi.org/10.1186/s13059-014-0550-8.26. Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. In the original publication , there wLately, comparative transcriptome analysis has demonstrated that bovine horns and cervid antlers most likely share the same cellular origin, namely from neural crest stem cells [18].Previous studies have demonstrated that sheep horn formation is initiated during the embryonic period .RNA sequencing (RNA-seq) is a high-throughput technology that provides a comprehensive view of the entire transcriptome, which contributes to a better understanding of embryonic development and the role of genes .The shape of sheep horn buds is similar to that of cattle horn buds [22].The featureCounts program in Subread (v2.0.3) was used to calculate the gene expression of horn buds and skin tissues [23].The package DESeq2 v1.36.0 of R software [24] was used to examine DEGs in horn buds and skin tissues.https://biit.cs.ut.ee/gprofiler/gost (accessed on 15 September 2022)) and KEGG Mapper (https://www.genome.jp/kegg/mapper/color.html (accessed on 15 September 2022)) tools.This was carried out on the g: Profiler and compared them with the DEGs identified in this study; these sets included the horn-related genes and proteins of sheep, goats, and cattle horns identified in previous studies .The embryonic period is crucial for the differentiation and formation of sheep horn [19].In this study, the histological results showed that the horn buds were significantly different from the forehead skin, having a thicker epidermis and more layers of epithelial cells, both of which findings have been previously reported . However, the vacuolated keratinocytes previously found reported in the horn buds of cow fetuses were not observed in the present study [22]. Meanwhile, in a previous study of Merino sheep, the vacuolated keratinocytes were not found in the development of horn buds from 75 days of gestation to adulthood [19].FOXL2 gene is involved in horn bud differentiation [36], and is associated with horn growth in goats [34]. Previous proteomic analysis has suggested that TNN is associated with the formation of horn deformity in sheep [17].It is also related to horn size, length, and shape in sheep , indicating that it plays a vital role in horn development during the embryonic period. The Venn diagram of DEGs and horn-related genes. A: DEGs; B: Horn-associated genes in transcriptome studies by Wang, Y. et al. [3], Pannetier, M. et al. [33], and Boulanger, L. et al. [34]; C: Horn-associated genes in proteome studies by He, X. et al. [17]; D: Horn-associated genes in genome studies by Li, X. et al. [1], Montgomery, G.W. et al. [10], Kijas, J.W. et al. , Wiedemar, N. et al. [13], L\u00fchken, G. et al. [14], He, X. et al. [15], Wang, X. et al. [29], Ren, X. et al. [30], Pailhoux, E. et al. [32], and Medugorac, I. et al. [35].Bioinformatics2014, 30, 923\u2013930. https://doi.org/10.1093/bioinformatics/btt656.23. Liao, Y.; Smyth, G.K.; Shi, W. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Genome Biol.2014, 15, 1\u201321. https://doi.org/10.1186/s13059-014-0550-8.24. Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Protein Sci.2022, 31, 47\u201353. https://doi.org/10.1002/pro.4172.25. Kanehisa, M.; Sato, Y.; Kawashima, M. KEGG mapping tools for uncovering hidden features in biological data. Nucleic Acids Res.2023, 51, D587\u2013D592. https://doi.org/10.1093/nar/gkac963.26. Kanehisa, M.; Furumichi, M.; Sato, Y.; Kawashima, M.; Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. The corrected order of the references is as below:The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Huynh et al., RSC Adv., 2020, 10, 18423\u201318433, https://doi.org/10.1039/D0RA01750G.Retraction of \u2018New synthesis of 2-aroylbenzothiazoles RSC Advances article due to irreproducibility of the reaction yields.Tien V. Huynh, Ngoc T. K. Luong, Duyen T. P. Nguyen, Tung T. Nguyen and Nam T. S. Phan hereby wholly retract this Khang V. Doan and Son H. Doan were informed about the retraction of the article, but have not responded to any correspondence regarding the retraction.3aa\u20133df) could not be reproduced when freshly opened reagents and solvents were used. It could be reasoned that the reported reagents were contaminated with unknown impurities, which have facilitated the reaction.The results shown in Table 2 (the synthesis of compounds The corresponding authors regret this carelessness and apologise for any inconvenience to readers.Signed: Tien V. Huynh, Khang V. Doan, Ngoc T. K. Luong, Duyen T. P. Nguyen, Son H. Doan, Tung T. Nguyen and Nam T. S. Phan.Date: 16th March 2023RSC AdvancesRetraction endorsed by Laura Fisher, Executive Editor,"} +{"text": "Nature Chemistry 10.1038/s41557-023-01136-x. Published online 16 February 2023.Correction to: Tetrahedron Lett. 59, 3926\u20133929 (2018) and Thavornpradit, S., Malinski, T. J. & Bergbreiter, D. E. Applications of poly(\u03b1-olefins) as solvents in organometallic chemistry. J. Organomet. Chem. 962, 122261 (2022). They have now been inserted as refs. 33 and 34 and the subsequent references renumbered. The new references and explanatory text have been included in the third-to-last paragraph of the Introduction, reading \u201cBergbreiter and co-workers reported that organolithium reagents could be used in poly(\u03b1-olefin) solvents, which have branched hydrocarbon structures, demonstrating enhanced stability and lower flammability33,34\u201d in the HTML and PDF versions of the article.In the version of this article initially published, two relevant articles were not cited: Malinski, J. & Bergbreiter, D. E. Safer solvents for organolithium reagents."} +{"text": "Surveillance of adverse events, healthcare-associated infections (HAI), and notifiable diseases is the foundation for controlling and preventing these occurrences. Typically, surveillance is carried out by trained professionals who manually review patient records and other data sources, using defined criteria for target events. The objective of this study is to present A.R.G.U.S. , a datamart that is part of the Datawarehouse for the Hospital Epidemiological Surveillance Unit (NUVEH) and the Hospital Infection Control Service (SCIH) project, from the Brazilian public hospital.A.R.G.U.S. is a cloud-based platform (AWS) that connects with the hospital system (MV), laboratory system (MATRIX and GAL), and utilizes automatic detection algorithms for HAI, Influenza-Like Illness (ILI), Severe Acute Respiratory Infection (SARI), and other notifiable diseases, generated through logistic regression models based on text mining of justifications for antimicrobial prescriptions, patient demographic data, and lists of patient ICD-10 codes. In addition to logistic regression, tests were conducted with probabilistic, naive Bayesian classifier.Text mining yielded 273 original terms, which were subsequently reduced to 173 root keywords for use in the modeling. Logistic regressions demonstrated an area under the ROC curve slightly below 0.8, while Na\u00efve Bayes classifiers showed an area below 0.7. As a result, Na\u00efve Bayes was excluded from A.R.G.U.S., which incorporates regression models along with algorithms utilizing ICD-10 codes for notifiable diseases. In parallel with the detection of HAI and notifiable diseases , an automated algorithm for antimicrobial auditing was implemented, optimizing the Antimicrobial Stewardship Program . Currently, access to the A.R.G.U.S. system is available only in Portuguese and can be obtained at https://www.risoleta.sacihweb.com/#/login.A.R.G.U.S. has significantly improved surveillance of healthcare-associated infections (HAI) and notifiable diseases. The Antimicrobial Stewardship Program was automated and optimized, enabling total control over antimicrobial use.All Authors: No reported disclosures"} +{"text": "Nature Communications 10.1038/s41467-023-36514-z, published online 02 March 2023Correction to: The original version of this Article contained an error in the captions of Figures 2, 3, and 4, in which the major tectonic boundaries incorrectly referred to reference 47. The correct version refers to reference 48 in place of 47. Reference 48 has been added asOre Geol. Rev.76, 212\u2013228 (2016).48. Korsch, R. J. & Doublier, M. P. Major crustal boundaries of Australia, and their significance for mineral systems targeting. http://pid.geoscience.gov.au/dataset/ga/133033 ) has been updated to reference 49.Original reference 48 (Hughes, A. Australian Operating Mines Map 2019. This has been corrected in both the PDF and HTML versions of the Article."} +{"text": "It presents clinically as impairment of intestinal motility, characterized by abdominal pain, vomiting, and delayed recovery of defaecatory function. For patients, this increases the risk of serious complications, such as pneumonia, venous thromboembolic events, and malnutrition2. For healthcare systems, it leads to a substantial economic burden associated with increased medical, nursing, dietitian, and laboratory costs3. Accordingly, postoperative ileus is now recognized as a research priority by expert and public stakeholder groups4.Postoperative ileus is a common and distressing complication after intestinal surgery5. A key challenge for researchers is the absence of a standardized and agreed framework to describe the effectiveness of new interventions in clinical studies6. Common outcomes include the time taken until first passage of flatus/stool, time until tolerance of oral diet, and the return of bowel sounds. It remains unclear, however, whether these are sufficiently relevant to patients and healthcare professionals when evaluating new treatments and implementing them in clinical practice7.Numerous clinical interventions have been evaluated in efforts to prevent postoperative ileus, but few have led to meaningful patient benefit8. The present report describes the international development and final content of an agreed core outcome set for postoperative ileus relevant to patients undergoing intestinal surgery.A solution to this problem is the development of an agreed core outcome set developed through patient\u2013clinician consensus. Core outcome sets provide a minimum set of outcomes that should be reported in all studies of a defined clinical condition and are supported by the Core Outcome Measures in Effective Trials (COMET) Initiative10. An extended description of the methods and results is provided in Appendix S1. An abridged summary is reported here.Research ethics approval was confirmed by the University of Sheffield Ethics Committee on 27 September 2019. A collaborative steering committee was convened with representation from Asia, Australasia, Europe, and North America, and included medical, allied healthcare professional, and patient investigators. The study was registered with the COMET Initiative and the protocol was reported previously11. The health condition was postoperative ileus; the population was adult patients undergoing intestinal surgery for any indication; and the setting was clinical studies assessing the effectiveness of a clinical intervention to reduce ileus. Intestinal surgery was considered to represent any intra-abdominal procedure via any surgical approach on the intestinal tract with or without formation of a stoma.The scope of the core outcome set was defined according to the Core Outcome Set\u2014Standards for Development recommendationsStakeholder representation was designed to reflect the multidisciplinary management of postoperative ileus as well as the challenge it presents on an international scale. Three key stakeholder panels were defined: patients with previous experience of intestinal surgery, allied healthcare professionals (including nurses and dietitians), and medical professionals . Medical and allied healthcare professionals were considered as two separate panels throughout the study to ensure that potentially diverging perspectives were captured. During each phase of the study, participants were recruited via national and international organizations as well as through social media.10. In phase 1, a long list of candidate outcomes was generated from a systematic review of previous literature, a series of four international patient and clinician focus groups, and consultation within the steering committee12. In phase 2, candidate outcomes were presented to stakeholders via a three-round Delphi survey with between-round feedback. Suggestions for additional outcomes were invited during round 1. During each round, participants voted on the importance of each outcome using a numerical rating scale (1\u20139), and those that fulfilled a predefined threshold of consensus were carried forward iteratively to the consensus meeting (Table 1). In phase 3, an online consensus meeting was convened to ratify the final outcome set. This was chaired by an independent chairperson and participants were sampled purposively to represent key stakeholder groups across an international setting. Final anonymized voting took place on the final composition and presentation of the set.The study consisted of three phases, in accordance with Delphi methodology, and was conducted between 17 January 2020 and 6 March 2021Table S1), analysis, and decision-making throughout. They encouraged patient engagement during the Delphi process and ensured that the patient voice remained central.Two patient representatives joined the steering committee, and contributed to the design, delivery .A total of 155 participants took part in round 1 of the Delphi survey . After completing round 1, 123 of 155 (79.4 per cent) took part in round 2, and 112 of 123 (91.1 per cent) in round 3. There were 15 participants in the final consensus meeting, including five patients, two allied healthcare professionals (1 nurse and 1 dietitian), and eight medical professionals 12. Six unique outcomes were added from stakeholder focus groups and 12 by the steering committee, resulting in 75 unique outcomes used to populate round 1 of the Delphi process.Seventy-three outcomes were identified from a systematic review of previous evidence which was refined by the steering committee to eliminate duplication (Box S1). During round 2, 70 outcomes (including those generated in the earlier round) were presented and nine reached the meeting threshold. The remaining 61 outcomes were re-presented during round 3 and one more reached the threshold. After consideration by the steering committee, six outcomes were considered to have \u2018borderline\u2019 consensus, and it was agreed to re-present these for a final decision at the meeting. The full Delphi results are shown in Tables S2 and S3.During round 1, a total of 75 outcomes were presented to participants and 13 reached the threshold to be considered at the consensus meeting. Eight unique outcomes were generated via free-text responses and were carried forward to round 2 (Table 1).Twenty-nine outcomes were considered by participants during the consensus meeting. Following detailed discussion, 23 outcomes that had achieved consensus during the Delphi process were ratified and two of six borderline outcomes reached consensus to be added according to the predefined threshold for consensus . It was also noted that four agreed outcomes were akin to risk factors rather than conventional outcomes of ileus. Consensus was reached to retain these to reflect essential contextual information required alongside other outcomes in the set .Table 3). Consensus was achieved to group outcomes into domains to reflect the patient journey and to rationalize the presentation of the set. Clustering of outcomes was achieved wholly through consensus, with the final wording of domains finalized by the steering committee. This produced a total of six domains along with three outcomes that remained ungrouped.A final core outcome set comprising 24 outcomes was agreed , M.J. Lee , S. Blackwell (Public Representative), R. Arnott , R.P.G. ten Broek , C.P. Delaney , N.N. Dudi-Venkata , R. Fish , D. Hind , D.G. Jayne , K. Mellor , A. Mishra , G. O\u2019Grady, , T. Sammour , G. Thorpe , C.I. Wells , A.M. Wolthuis , N.S. Fearnhead , S. Adegbola, G. Bagaglini, M. Bath, N. Bibby, C. Bisset, N. Blefari, N.S. Blencowe, W. Bolton, J.P. Bulte, J. Burch, M. Campanelli, O. Cano-Valderrama, J. Carver, C. Challand, S. Chan, S. Chandler, D. Clerc, P. Coe, D. Cox, K.L.R. Cross, A. Culkin, V. Cuthill, S. Daniels, A. Dawson, L. Dawson, F. Dixon, C. Downey, T. Drake, S. Duff, G. Dunning, E. Espin-Basany, M.D. Evans, M. Fakhrul-Aldeen, N. Fisher, S. Fleetwood-Beresford, G. Gallo, Z. Garoufalia, R. George, J. Han, D. Harji, R. Harmston, D.A. Harris, M. Mohammed, J. Helliwell, J. Hepburn, P. Herrod, N. Horwood, C. Keane, S. Kelly, H.M. Kroon, M.D.S. Lonsdale, G. Major, J. Mattison, A. Lawson McLean, M. Millan, S. Limbert, F. McDermott, A. Mehraj, C. Moriarty, S. Moug, E. Murray, M. Naylor, D. Nepogodiev, J. Oliver, D. Pandey, F. Pata, H.M. Paterson, A. Peckham-Cooper, G. Pellino, P. Pockney, V.K. Proctor, D. Proud, V. Rew, M. Ruteg\u00e5rd, K. Sahnan, A. Sayers, L. Siragusa, R.W. Smillie, J. Spratt, D. Swain, S. Taylor, P. Tejedor, O. Thomas, J. Thompson, K. Tsimogiannis, D. Tuohey, R. Vissapragada, M.U. Younis, P.G. Vaughan-Shaw, K. Whyte, K. Wheelband, A. Williams, A. Yates, R. Young.znac052_Supplementary_DataClick here for additional data file."} +{"text": "Polygonaceae, the phylogenetic positions of most genera and their relationships have been resolved. However, the monotypic genus Harpagocarpus has never been included in any published molecular phylogenetic studies. In the present study, we adopt a two-step approach to confirm the phylogenetic placement of Harpagocarpus using two datasets: (1) a concatenated dataset of three chloroplast DNA (cpDNA) regions for Polygonaceae and (2) a combined cpDNA dataset of five sequences for Fagopyrum. Our analyses confirm the previous hypothesis based on morphological, anatomical and palynological investigations that Harpagocarpus is congeneric with Fagopyrum and further reveal that H.snowdenii (\u2261 F.snowdenii) is sister to the woody buckwheat F.tibeticum. Within Fagopyrum, three highly supported clades were discovered and the first sectional classification was proposed to accommodate them: sect. Fagopyrum comprises the two domesticated common buckwheat (F.esculentum and F.tataricum) and their wild relatives which are characterised by having large corymbose inflorescences and achenes greatly exceeding the perianth; sect. Tibeticum, including F.snowdenii and F.tibeticum, is characterised by the achene having appurtenances along the ribs, greatly exceeding the perianth and the perianth accrescent in fruit; sect. Urophyllum contains all other species of which the achenes were completely enclosed in the perianth. This study is very helpful to understand the phylogeny of the Fagopyrum and sheds light on the future study of taxonomy, biogeography, diversification and character evolution of the genus.In the context of the molecular phylogeny of Polygonaceae, a family of the flowering plants known as the buckwheat family, can be easily distinguished by its ocrea, orthotropous ovules, trigonal achenes and quincuncial aestivation Rchb., Rubrivena M.Kr\u00e1l and Emex Neck. ex Campd. S.P.Hong for H.snowdenii after concluding from additional palynological research. Though this treatment has been followed in some literature , which provided us an invaluable opportunity to investigate the phylogenetic position of Harpagocarpus, based on additional molecular data. We adopted two steps of phylogenetic analyses to infer the generic and specific affinities of H.snowdenii. Firstly, we used three chloroplast DNA (cpDNA) markers to present the backbone phylogeny of Polygonaceae and affirmed the position of Harpagocarpus in Fagopyrum. Subsequently, based on five cpDNA regions , we further reconstructed the phylogeny of Fagopyrum and clarified the accurate specific relationships of F.snowdenii within Fagopyrum.In the present study, we obtained a few precious pieces of leaf materials of matK, rbcL and trnL-F sequences, which have been extensively used in previous studies (e.g. cpDNA dataset (D1) for reconstructing the backbone phylogeny of Polygonaceae. The ingroup taxa were selected from the entire family to cover all recognised tribal clades using five cpDNA regions , with an expanded sampling of Fagopyrum aiming for a more accurate placement of H.snowdenii (= F.snowdenii). The ingroups of D2 dataset included 33 taxa of Fagopyrum covering most of the recognised species in the genus and the outgroup taxon was set as Pteroxygonumgiraldii Damm. et Diels according to the results presented in As the analyses of the D1 dataset demonstrated that PCR). The PCR reactions and amplification protocol followed PCR Product Purification Kit . Sequencing reactions were conducted with the forward and reverse PCR primers using the DYEnamic ET Terminator Cycle Sequencing Kit with an ABI PRISM 3730 automatic DNA sequencer . Both strands of the DNA were sequenced with overlapping regions to ensure that each base was unambiguous. Electropherograms were assembled and consensus sequences were generated with Geneious Prime 2022.0.2 platform.Total genomic DNA was extracted from fresh or silica gel dried leaves following the manufacturer\u2019s specifications of the DNEasy Plant Mini Kit . After extraction, the DNA was resuspended in double-distilled water and kept at -40 \u00b0C for polymerase chain reaction and Bayesian Inference (BI).Phylogenetic analyses were conducted, based on the combined analyses because analyses . The datML and BI analyses were carried out using RAxML-HPC2 version 8.2.9 set to 1000. The BI analysis was executed with most of the default parameters, but manually setting the following: the best substitution types (Nst) and rate distribution models (rates) that were determined by the jModelTest version 2.1.7 , of which 1756 are variable (42.14%) and 1181 are parsimony-informative (28.34%). The ML and BI analyses, based on dataset D1, generated nearly identical topologies and posterior probabilities (PP) values marked on each branch, respectively is well supported as monophyletic . Within Polygonaceae, the first branch, represented by Symmeriapaniculata Benth., is Symmerioideae which is sister to a large clade comprising Eriogonoideae and Polygonoideae. Within Eriogonoideae, six tribes are recovered with Brunnichieae emerging as the first divergent clade and then subsequently followed by Leptogoneae, Coccobobeae, Triplarideae, Gymnopodieae and Eriogoneae+Pterostegieae. Pterostegiadrymarioides Fisch. & C.A.Mey. of Pterostegieae is shown to be nested within Eriogoneae in our analyses. In Polygonoideae, all seven tribes are fully supported as monophyletic , of which 735 are variable (11.52%) and 428 are parsimony-informative (6.71%). ML and BI trees generated from the D2 dataset yielded similar topologies Gaertn. and F.dibotrys (D.Don) H.Hara , the second one is formed by F.snowdenii (\u2261 Harpagocarpussnowdenii) and F.tibeticum (A.J.Li) Adr.Sanchez & Jan.M.Burke and the third includes the remaining taxa of the genus.The combined dataset D2 has 31 aligned sequences and comprises 6378 characters rum Figs . The addigations .H.snowdenii has sagittate to ovate-triangular leaf blades, seven palmate veins, large and clearly exerted fruits from the persistent tepals and broad cotyledons, which are very similar to those traits presented in Fagopyrum species Meisn. (= F.dibotrys), F.esculentum and F.tataricum and characterised by having corymbose inflorescences with many branching and dense flowers and the achene greatly exceeding the perianth, while the other group is composed of other species (including F.urophyllum (Bureau & Franch.) H.Gross) having raceme-like inflorescences with sparse flowers and the achene completely enclosed in perianth (cymosum group and the urophyllum group defined by nrITS) and cpDNA region rbcL-accD. Other molecular studies, no matter using isozyme variability and RFLP Fagopyrumand RFLP , cpDNA sequences , nuclearequences and compequences , all cleF.snowdenii and F.tibeticum, was discovered, which is sister to the \u2018Urophyllum\u2019 clade growing along the fruit ribs and smaller pollen grains than the other Fagopyrum species Meisn., Monogr. Polyg. 43, 61. 1826.] \u2013 Type: Fagopyrumesculentum Moench (\u2261 Polygonumfagopyrum L.). Mill., Gard. Dict. Abr., ed. 4, 495. 1754 . = Parapteropyrum A.J.Li, Acta Phytotax. Sin. 19: 330. 1981 \u2013 Type: Parapteropyrumtibeticum A.J.Li [\u2261 Fagopyrumtibeticum (A.J.Li) Adr.Sanchez & Jan.Burke]. = Taxon classificationPlantaeCaryophyllalesPolygonaceae\ufeff850B40D3-92E3-59CF-91DB-28396A7F7AA5Fagopyrumesculentum Moench. (\u2261 Polygonumfagopyrum L.).This section is characterised by having large corymbose inflorescences with many branches and dense flowers and large achenes greatly exceeding the persistent perianth.F.dibotrys, F.esculentumsubsp.esculentum, F.esculentumsubsp.ancestrale, F.homotropicum and F.tataricum.Bhutan, India, Myanmar, Nepal, Pakistan, Thailand and Vietnam of southern and south-eastern Asia and southern and south-western China.Taxon classificationPlantaeCaryophyllalesPolygonaceae\ufeffBo Li & M.L.Zhousect.nov.F19BE93D-AD33-51E9-8E0E-E79D27778999urn:lsid:ipni.org:names:77315008-1Fagopyrumtibeticum (A.J.Li) Adr. Sanchez & Jan. Burke (\u2261 Parapteropyrumtibeticum A.J.Li).The new section is characterised by having raceme-like inflorescences with sparse flowers, large achenes with appurtenances (wings or setae) along the ribs and greatly exceeding the perianth and persistent perianth accrescent in fruit.F.snowdenii and F.tibeticum.F.snowdenii) and Tibet of south-western China (F.tibeticum).Cameroon, Kenya, Rwanda, Tanzania and Uganda of Africa H.Gross (\u2261 Polygonumurophyllum Bureau & Franch.).This new section is characterised by having raceme-like, spicate, capitate or paniculate inflorescences with mostly sparse or rarely dense flowers and achenes completely enclosed in the persistent perianth.F.callianthum Ohnishi, F.capillatum Ohnishi, F.caudatum (Sam.) A.J.Li, F.crispatifolium J.L.Liu, F.densovillosum J.L.Liu, F.gilesii (Hemsl.) Hedberg, F.gracilipedoides Ohsako & Ohnishi, F.gracilipes (Hemsl.) Dammer, F.jinshaense Ohsako & Ohnishi, F.leptopodum(Diels)Hedbergvar.leptopodum, F.leptopodumvar.grossii (L\u00e9vl.) Lauener & D.K.Ferguson, F.lineare (Sam.) Haraldson, F.longistylum M.L.Zhou & Y.Tang, F.longzhoushanense J.R.Shao, F.luojishanense J.R.Shao, F.macrocarpum Ohsako & Ohnishi, F.pleioramosum Ohnishi, F.pugense Y.Tang, F.qiangcai D.Q.Bai, F.rubifolium Ohsako & Ohnishi, F.statice H.Gross, F.urophyllum (Bureau & Franch.) H.Gross, F.wenchuanense J.R.Shao.Guizhou, Sichuan and Yunnan Provinces of southwest China."} +{"text": "Author Contributions: A.K.K. conceptualized, designed, performed, and analyzed the results and wrote the manuscript. P.A., A.B., T.K., S.B., S.S., N.K.P., R.N., A.G., N.K., D.G.M.J., L.S., B.B., K.M.-K. and T.C.D. performed part of the experimental work and/or analyzed the results T.K., designed, performed, analyzed and wrote AFM experiments. S.B. conceptualized and revised AFM experimental outcome. M.S. conceptualized the study, wrote, and revised the manuscript. Y.L. designed, performed, and wrote up the immunocytochemistry experiment and also revised the manuscript. All authors have read and agreed to the published version of the manuscript.\u201cYan Li\u201d was not included as an author in the original publication . Dr. YanThe authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Amaranthus caudatus and the related taxa are presented. Types are designated for names A. caudatus var. albiflorus (neotype at RO), A. caudatus var. atropurpureus (neotype at GH), A. caudatus var. gibbosus (neotype at RO), A. dussi (neotype at NAP), and A. edulis (lectotype at LP). Holotypes are indicated for the names A. caudatus var. pseudopaniculatus f. oblongipetalus (EA), A. caudatus var. pseudopaniculatus f. pseudopaniculatus (EA), A. caudatus subsp. saueri (PR), and Amaranthus edulis var. spadiceus (CORD). The names A. caudatus var. albiflorus, A. caudatus var. atropurpureus, A. caudatus subsp. saueri, A. dussi, and Amaranthus edulis var. spadiceus are considered as hererotypic synonyms of A. caudatus. On the basis of morphological, cytological, and molecular data, the taxa caudatus, mantegazzianus, and gibbosus are here proposed to be treated as different species. A new name\u2014Amaranthus baileyanus\u2014is proposed for A. caudatus var. gibbosus because of a previous and validly published Amaranthus gibbosus.Nomenclatural and taxonomic issues concerning Amaranthus L. (Amaranthaceae Juss.) is a genus comprising 70\u201375 species, of which approximately half are native to the Americas red, clustered in more or less separated fascicles or heads\u201d (var. gibbosus). The word \u201cHort.\u201d (= Hortorum) is reported just after each varietal name and it indicates that the plants were cultivated. Note that Bailey, in his previous (year 1909) Cyclopedia of American Horticulture |Trade Name Amaranthus gibbosus|Nich Rochester\u2026 July 22 1890 [handwritten] | L. H. BAILEY [printed]\u201d. Two further annotations, directly occurring on the sheet, are \u201cA. caudatus mna\u201d , which was probably added by Mabel W. Allen who was here at Cornell in the 1930s or so , and \u201cCYCLOPEDIA OF AMERICAN HORTICULTURE [printed] | A. paniculatus\u201d , where A. paniculatus L. . As a consequence, it cannot be considered for the lectotypification purpose of the var. gibbosus. No further original material was traced for Bayley taxa and, as a consequence, neotypifications are required under Art. 9.8 of ICN as follows:(1)Amaranthus atropurpureus: since the colour of the leaves often change after exsiccation of amaranths and the diagnostic character of this variety is \u201cFoliage blood-red\u201d which are now subject of living interest or likely to be introduced\u2026\u201d [oduced\u2026\u201d (p. vi).Current distribution area. No data about Amaranthus baileyanus appear to be published. On the basis of my proposed neotypification, this species occurs in Eastern Europe (Serbia), where I directly saw a population in the field (collection was here designated as the neotype of A. baileyanus). Moreover, I traced two specimens from France collected more than 80 years ago (see the following \u201cSelected specimens examined\u201d). The species is here considered as a casual alien for Europe. Further investigations will be necessary to provide data on the chorology of A. baileyanus.Selected specimens examined. France: Puy-de-D\u00f4me, September 1936, Ch. D\u2019Alleizette s.n. ; Val-d\u2019Oise, Maffliers, 27 October 1940, M. P. Jovet s.n. .Amaranthus mantegazzianus Passer., Hor. Parm.: 4. 1865 \u2261 Amaranthus caudatus L. subsp. mantegazzianus (Passer.) Hanelt, Kulturpflanze 16: 128 1968.A.T. Hunziker 2555 (CORD00002607 (image!), Hunziker [Neotype (designated by Hunziker (p. 105)Hunziker (p. 105)Amaranthus edulis Speg., Physis (Buoenos Aires) 3: 163. 1917.= s.d., C. Spegazzini s.n. (LP002715 (image!), Lectotype (designated here): Argentina, cultivado en la Plata, Amaranthus edulis Speg. Var. spadiceus Hunz., Revista Argent. Agron. 10: 330. 1943.= Holotype. Argentina, Tafi, Tucuman, \u201cCultivado por su semillias alimenticias. De + 1.50 m de altura\u201d, s.d., A.T. Hunziker 2552 (CORD00009356 (image!); Amaranthus edulis Speg. Var. pseudopaniculatus f. pseudopaniculatus Suessenguth in Suessenguth & Merxm\u00fcller 1951: 71, Mitt. Bot. Staats., Munchen 1: 71. 1951.= Holotype. Tanzania, Amani, 2900 ft., 24 March 1941, P.J. Greenway 993 (EA no. 6154 (image!); Amaranthus edulis Speg. Var. pseudopaniculatus f. oblongipetalus Suessenguth in Suessenguth & Merxm\u00fcller 1951: 71, Mitt. Bot. Staats., Munchen 1: 71. 1951 .= Holotype. Tanzania, Amani, 2900 ft., 24 March 1941, P.J. Greenway 995 (EA no. 6155 (image!); Native distribution area. Unknown, but likely South America (Argentina).Current distribution area. The holotypes of Amaranthus edulis var. pseudopaniculatus came from Tanzania, whereas the specimens below listed were from Ethiopia ). I here consider A. mantegazzianum as a probably alien species for Africa. Further investigations will be necessary to give a distribution of Amaranthus mantegazzianus out of its native range.Iamonico as a synSelected specimen examined. Ethiopia: In ruderatis prope Adoam, 1 November 1844, Schimper 1535 (P00482809); ibidem ."} +{"text": "Jirun Sun was not included as an author in the original publication . The corAuthor Contributions: Conceptualization, X.W., S.Y. and J.S.; methodology, S.Y. and J.S.; validation, X.W.; formal analysis, X.W.; investigation, X.W.; resources, X.W. and J.S.; data curation, X.W.; writing\u2014original draft preparation, X.W.; writing\u2014review and editing, X.W. and S.Y.; visualization, X.W. All authors have read and agreed to the published version of the manuscript.In the original publication, the funder, NIH, grant number DE023752 to Jirun Sun, was not included. The updated funding section appears here. Funding: This research was funded by NIH, grant number DE023752.In addition to affiliations 1 and 2, the updated affiliations should include the following:3 The Forsyth Institute, Cambridge, MA 02142, USA4 Harvard School of Dental Medicine, Boston, MA 02115, USAThe authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "M., Varela, S., Mart\u00ednez Cortizas, A. M., & Fragoso, J. M. V. (2023). Mammal traits and soil biogeochemistry: Functional diversity relates to composition of soil organic matter. Ecology and Evolution, 13, e10392. sobral.bernal.mar@gmail.com\u201d was incorrect. This should have read: \u201cmar.sobral.bernal@usc.es\u201d.In the correspondence data of the \u201cAuthors' list\u201d section, the email address \u201cWe apologize for this error."} +{"text": "Aongstroemia and Dicranella as polyphyletic, indicated the need for changes in their circumscription and provided new morphological evidence to support the formal description of newly recognized lineages. Following up on these results, the present study adds another molecular marker, the highly informative trnK\u2013psbA region, to a subset of previously analyzed taxa and presents molecular data from newly analyzed austral representatives of Dicranella and collections of Dicranella-like plants from North Asia. The molecular data are linked with morphological traits, particularly the leaf shape, tuber morphology, and capsule and peristome characters. Based on this multi-proxy evidence, we propose three new families and six new genera to accommodate the described species according to the revealed phylogenetic affinities. Additionally, we amend the circumscriptions of the families Aongstroemiaceae and Dicranellaceae, as well as the genera Aongstroemia and Dicranella. In addition to the monotypic Protoaongstroemia that contains the newly described dicranelloid plant with a 2\u20133-layered distal leaf portion from Pacific Russia, P. sachalinensis, Dicranella thermalis is described for a D. heteromalla-like plant from the same region. Fourteen new combinations, including one new status change, are proposed.The recent molecular phylogenetic study of the families Aongstroemiaceae and Dicranellaceae, which resolved the genera Entosthodon Schw\u00e4gr. ex Hornsch., Physcomitrium (Brid.) Brid. ,,trnL\u2013trntions in that we y Mitten , accessiluded in . We alsoThe concatenated matrix consisted of 6381 aligned sites, of which 563 belonged to L partition, 975 to T partition, 728 to R, 2899 to K, and 1216 to N. Indels scored for the L, R, and N partitions yielded an additional 193 binary sites, and 251 indels were scored for the T and 218 for the K partition. The partitions corresponding to the dataset used by Bonfim-Santos et al. , i.e., LChrysoblastella chilensis, Neodicranella hamulosa, and Archidium + Leucobryaceae and Grimmiales clades. Hence, we present here the results representing the total evidence of the fully concatenated dataset (LTRKN) in The trees inferred from the combined L, R, and N data, and those with an added T region dataset, had essentially identical topology, with generally higher support values from the expanded dataset. The addition of indel data generally further improved the support values, without changes in topology at the supported nodes, however only when T indel data were not considered. At the same time, the trees estimated from the separate analysis of K data, which again had generally higher support node values in the version with SIC-coded indels included, yielded a topological incongruence compared to the trees derived from LTRN data, with respect to the estimated affinities of Pseudoditrichum mirabile was newly assessed as unresolved among the basal protohaplolepidous clades and the clade containing all other analyzed taxa, i.e., Bryoxiphium + rest of Dicranales incl. Grimmiales), rather than being found in the basal grade of Dicranales. This position was shared by the analyses resulting from the LTRN and K datasets were found in the maximally supported clade with European accessions, although three accessions collected in the heart of the permafrost zone of northeast Asia differed in several substitutions, despite the absence of notable morphological differences, except for the slightly more robust habit. European accessions of the previously unanalyzed D. humilis from the Czech Republic and Russian Leningrad Province proved identical and distinct from the rest of the analyzed accessions of D. rufescens and Far Eastern accessions earlier referred to D. humilis based on their seemingly inclined capsules . Additionally, the accession FDt119 from plants morphologically approaching D. humilis collected in Sakhalin Island was found to be molecularly distinct, in a sister position to the maximally supported D. rufescens clade. The topology between the maximally supported D. rufescens + humilis clade, D. crispa + subulata clade, and the crown clade of Dicranales has not been resolved, even with our deeper molecular sampling, yet the analysis of trnK data alone (D. rufescens + humilis plus D. crispa + subulata lineages. Stronger support (BI PP 1 but without support from ML) was found for the clade containing these two lineages and the clade containing the core Dicranales. The ambiguous affinities of these two lineages might partly result from the ambiguous affinities of the Archidiaceae + Leucobryaceae clade, which was resolved in the sister position to the clade containing Grimmiales based on the LTRN data (now with BS 94/PP 1 support), as opposed to the unsupported (BS < 50/PP 0.79) sister position of the Archidiaceae + Leucobryaceae clade to the rest of the Dicranales, excluding D. rufescens + humilis and D. crispa + subulata lineages, in the analysis of K data alone. The signal from LTRN data was stronger than that of K data, weakening the support for Archidiaceae/Leucobryaceae plus Grimmiales clade to BS 67/PP 0.94 in the combined LTRKN analysis.In contrast to this study, after reconsidering the reading of several bases in the raw chromatograms, the position of datasets . Additiota alone yielded Amphidium and the rest of the core Dicranales clade. The same is true for the three larger clades within the core Dicranales, the first one including Schistostega, Rhabdoweisiaceae, Ditrichaceae, Pottiaceae, Bruchiaceae, and a maximally supported clade containing accessions of Rhamphidium, Symblepharis krausei, and Dicranella vaginata; the second containing Dicranaceae, Fissidentaceae, Chrysoblastella, Bryowijkia, and Dicranellaceae; and the third containing Aongstroemiaceae.Support for the core Dicranales clade has grown substantially in both ML (BS 85\u2013100 according to the dataset) and BI (PP 1), and similar support was obtained for the sister relationship between Dicranella s.l., except for the genus in its amended delimitation itself, and the newly analyzed accession of Dicranella polii from Madagascar appeared in a poorly supported clade with two accessions of the genus Garckea, which itself appeared nested within a maximally supported clade containing accessions of Microcampylopus, Campylopodium, and Leptotrichella flaccidula. This clade is resolved in sister position to the clade containing Aongstroemia filiformis s.lat. accessions. The Madagascan and Reunion accessions of that species appear molecularly distinct from the Neotropical accessions, which earlier were recognized as A. jamaicensis M\u00fcll. Hal. Within the Dicranella s.str. clade, accessions of D. cerviculata formed a clade sister to the remaining accessions of the genus. Within the latter, two molecularly identical accessions of D. heteromalla/Campylopus pyriformis-like plants from Southern Kuril Islands are separated in a maximally supported clade and are described below as Dicranella thermalis. The maximally supported sister clade to the D. thermalis clade consists of (1) the nearly maximally supported clade containing accessions of D. curvipes and (2) the unsupported clade containing the accessions of D. heteromalla. Within this clade, two smaller clades can be recognized, one with high support containing both European and non-European plants referable to this species, and the other unsupported clade containing only accessions from the Russian Far East, which might in the future receive formal status upon a detailed account of their molecular and morphological variability.The nearly maximally supported (BS 98\u2013100/PP 1) Dicranellaceae clade does not contain northern representatives of Dicranella varia s.lat. + D. howei + D. pacifica clade and the rest of the taxa was confirmed, yet the clade containing Aongstroemiaceae without the D. varia group now only has weak support (BS 63\u201378 only from K data and PP 0.67\u20130.97 according to dataset and indel scoring), with respect to the inclusion of the newly analyzed basalmost lineage containing the plants described below as a new genus, Protoangstroemia. Within the D. varia group, four maximally or nearly so supported lineages could be recognized. Apart from D. varia and D. howei, the newly analyzed D. pacifica appeared sister to D. varia + howei clade, and four accessions, containing the RF42, which earlier was assigned to D. varia but now is referred to Dicranella varia var. obtusifolia Berggren raised to the species rank below, form a lineage sister to the rest of the entire D. varia group. Within the Aongstroemiaceae s.str. clade, the basal grade consists of Protoangstroemia and the maximally supported lineages of Diobelonella, Dichodontium, and Neodicranella. However, the clade containing accessions of Neodicranella appears in a different position in the analysis of LTRN and K data contains the Dicranella grevilleana + Aongstroemia longipes, Dicranella schreberiana var. robusta, D. schreberiana var. schreberiana, Hygrodicranum bolivianum, H. herrerae, and Dicranella campylophylla + D. hookeri + Polymerodon andinus clades. Additional accessions of Aongstroemia longipes, Dicranella grevilleana, D. schreberiana var. schreberiana, D. campylophylla, and D. hookeri support the distinctness of Aongstroemia longipes from Dicranella grevilleana, Dicranella schreberiana var. robusta from var. schreberiana, and of D. campylophylla from D. hookeri, yet a more detailed study of taxa in this group needs to be performed in the future with respect to one isolated accession of Dicranella schreberiana s.lat. from Russia (RF40), the similarly isolated accession of D. hookeri RF65, and the nested position of D. campylophylla TJH13 within the clade, which otherwise contained specimens referable to D. hookeri.Within the now maximally (except for ML BS 87 in the LTRN-based tree) supported Aongstroemiaceae sensu , the sisdata cf. , essentiOur trees are largely congruent with those published by ,23, yet Dicranella staphylina. The totally orphaned position of Dicranella staphylina within the system of haplolepidous mosses came as one the most surprising results of the phylogenetic reconstruction by In locis paucis prope B\u00e4rwalde Neomarchicae. \u2261 Anisothecium humile (R. Ruthe) Lindb., Meddeland. Soc. Fauna Fl. Fenn. 14: 74. 1887 \u2261 Aongstroemia humilis (R. Ruthe) M\u00fcll. Hal., Gen. Musc. Frond. 323. 1900. \u2261 Dicranella rufescens subsp. humilis (R. Ruthe) Kindb., Eur. N. Amer. Bryin. 2: 209. 1897.Dicranellopsidaceae Bonfim Santos, Siebel & Fedosov, fam. nov.\u2013Type: Dicranellopsis Bonfim Santos, Siebel & FedosovDiagnosis: This family differs from the other families of haplolepideous mosses in possessing the following combination of characters: plants small to medium-sized; stems with central strand; leaves with widened to vaginate leaf bases, abruptly narrowed to subulate leaf acumina; leaf margins plane; costae with two stereid bands and guide cells; leaf lamina bistratose distally; laminal cells elongate, smooth; sexual condition dioicous; red setae; ribbed capsules; Dicranoid peristome and revoluble annulus.The family is currently considered monogeneric.Dicranellopsis Bonfim Santos, Siebel & Fedosov, gen. nov.\u2013Type: Dicranellopsis subulata (Hedw.) Bonfim Santos, Siebel & FedosovEtymology: The generic name originates from Dicranella, the genus to which the species of Dicranellopsis had been assigned previously, and the suffix -opsis , referring to the morphological similarity between the genera.Diagnosis: Species combined in the newly established genus differ from other dicranelloid mosses in possessing a combination of widened to vaginate leaf bases and subulate leaf tips, plane leaf margins, costae with two stereid bands and guide cells, bistratose upper leaf lamina, red setae, ribbed capsules and revoluble annulus.Description: Plants yellowish green to dark green, lacking red pigmentation. Stems with central strand. Leaves with oblong bases abruptly tapering into a long, channeled, subulate acumina, upper stem leaves sheathing, erect to squarrose-flexuose, patent or secund, crispate or not when dry; margins entire or very slightly denticulate at leaf tip, plane, unistratose; costae percurrent to short excurrent, sharply delimited from leaf lamina, with dorsal and ventral epidermis, guide cells and dorsal and ventral or only dorsal stereid band; distal leaf lamina bistratose, median leaf cells linear. Rhizoidal tubers, when present, dark brown, irregularly shaped without protruding cells, curved. Perichaetial leaves resemble upper stem leaves. Capsules erect to slightly inclined, symmetric or distinctly curved, not strumose, strongly longitudinally ribbed, with more or less differentiated exothecial bands and quadrate to short rectangular, rather thin-walled cells between them. Annulus differentiated in 2\u20133 rows of widened cells, revoluble. Peristome dicranoid.Accepted species:Dicranellopsis crispa (Hedw.) Bonfim Santos, Siebel & Fedosov, comb. nov. \u2261 Dicranum crispum Hedw. in Sp. Musc. Frond. 132. 1801\u2013Lectotype: Sweden, J.F. Ehrhart s.n. M\u00fcll. Hal. in Syn. Musc. Frond. 1: 439. 1848 \u2261 Dicranella crispa (Hedw.) Schimp. in Coroll. Bryol. Eur. 13. 1856 \u2261 Leptotrichum crispum (Hedw.) Mitt. in J. Proc. Linn. Soc., Bot., Supplementary 1: 158. 1859 \u2261 Cynodontium crispum (Hedw.) Mitt. in J. Proc. Linn. Soc., Bot. 8: 15. 1864 \u2261 Anisothecium crispum (Hedw.) C.E.O. Jensen in Skand. Bladmossfl. 314. 1939, nom. illeg., non Lindb. in Utkast Eur. Bladmoss. 33. 1878.0040017, : Figure 0040017, : Figure Dicranellopsis subulata (Hedw.) Bonfim Santos, Siebel & Fedosov, comb. nov. \u2261 Dicranum subulatum Hedw. in Sp. Musc. Frond. 128. T. 34. f. 1\u20135. 1801\u2013Lectotype: Sweden, Swartz s.n. B\u00e9h\u00e9r\u00e9 in Muscol. Rothom. 29. 1826 \u2261 Dicranum heteromallum var. subulatum (Hedw.) Wallr. in Fl. Crypt. Germ. 1: 160. 1831 nom. illeg. \u2261 Aongstroemia subulata (Hedw.) M\u00fcl. Hal. in Syn. Musc. Frond. 1: 433. 1848 \u2261 Dicranella subulata (Hedw.) Schimp. in Coroll. Bryol. Eur. 13: 1856 \u2261 Leptotrichum subulatum (Hedw.) Mitt., in J. Proc. Linn. Soc., Bot., Supplementary 1: 9. 1859 \u2261 Cynodontium subulatum (Hedw.) Mitt. in J. Proc. Linn. Soc., Bot. 8: 15. 1864.0040102, : Figure 0040102, : Figure Dicranellaceae Stech in Nova Hedwigia 86: 14. 2008\u2013Type: Dicranella Schimp.Campylopodium Besch. (only C. medium studied), Cladophascum Dixon, Dicranella Schimp. Eccremidium Wilson (only E. floridanum studied), Garckea M\u00fcll. Hal., Leptotrichella Lindb. (only L. flaccidula studied), Microcampylopus Fleisch., Bryopalisotia Bonfim Santos & Fedosov.Accepted genera: Bryotestua Th\u00e9r. & P. de la Varde. As for Trichodontium (Dixon) Fife, see the Discussion.Tentatively included genus (pending molecular confirmation): Description: Plants small to medium-sized, growing in turfs. Acrocarpous or cladocarpous. Central strand present. Leaves appressed or erect-spreading, often flexuose or falcate-secund, narrowly lanceolate, often subulate. Lamina cells rectangular, smooth, not porose. Alar cells not differentiated. Costa single, strong, (sub-)percurrent to (long) excurrent, with guide cells, dorsal and ventral stereid bands and differentiated ventral and dorsal epidermis. Dioicous or autoicous. Seta elongate, erect, sinuose or arcuate, or short, erect or curved. Capsule erect to horizontal or pendulous, symmetric or gibbous, occasionally strumose, smooth or plicate, ovoid to short-cylindric with operculum conic to long-rostrate, or globose with operculum dome-shaped to hemispheric with a blunt apiculus. Stomata present or absent. Peristome dicranoid or absent. Spores usually papillose, sometimes warty. Calyptra cucullate or mitrate.The following synopsis only includes the genera where taxonomic novelties are proposed.Dicranella Schimp. in Coroll. Bryol. Eur. 13. 1856\u2013Type: Dicranella heteromalla (Hedw.) Schimp.Dicranella cerviculata (Hedw.) Schimp., D. curvipes (Lindb.) Ignatov, D. heteromalla (Hedw.) Schimp., D. thermalis Fedosov & Ignatova (see below).Accepted species: Dicranella campylophylla (Taylor) A. Jaeger, D. crispa (Hedw.) Schimp., D. grevilleana (Brid.) Schimp., D. hookeri Cardot, D. howei Renauld & Cardot, D. humilis Ruthe, D. pacifica W.B. Schofield, D. riparia (H. Lindb.) M\u00e5rtensson & Nyholm, D. rufescens (With.) Schimp., D. schreberiana (Hedw.) Hilf. ex H.A. Crum & L.E. Anderson, D. staphylina H. Whitehouse, D. subulata (Hedw.) Schimp., D. varia (Hedw.) Schimp.Excluded species: Dicranella polii Renauld & Cardot and D. vaginata (Hook.) Cardot, for which our molecular phylogenetic data suggest placement outside Dicranella as recognized here, but additional sampling is needed to assign the generic affinities, as discussed above.Species with uncertain placement: all other accepted species (cf. ), pendinDicranella thermalis Fedosov, Ignatova & Jan Ku\u010dera, sp. nov. . .Etymology: The species name refers to the typical habitat of the species at the type locality.Description: Plants medium-sized, stems up to 3 cm, single, with well-developed central strand, evenly foliate, tomentose in lower part. Leaves more or less appressed when dry, spreading when wet, gently falcate-secund, 2.5\u20133.2 \u00d7 0.25\u20130.35 mm, widest at base, from lanceolate base gradually tapering into canaliculate subulate acumen; margins plane, unistratose, weakly and bluntly toothed throughout or only in upper half, near apex with double teeth: costae strong, occupying 1/3\u20131/2 of leaf base, rather indistinctly delimited from the leaf lamina, with one row of guide cells, two stereid bands, and differentiated dorsal and ventral epidermis; sometimes ventral epidermis immediately covering guide cells or guide cells forming surface of costa ventrally; leaf lamina partly or completely bistratose distally, upper leaf cells 24\u201338 \u00d7 5\u20136 \u00b5m, elongate-rectangular, smooth, moderately thick-walled; basal leaf cells of the same length and 8\u201311 \u00b5m wide. Sexual condition and sporophytes unknown.Differentiation: We did not find more characteristics to differentiate this molecularly distinct species from Dicranella heteromalla than those specified in the diagnosis. D. thermalis resembles Campylopus pyriformis (Schultz) Brid. in having wide costae, undifferentiated alar regions, and thin-walled cells with wide lumen on a ventral surface in the basal portion of leaf. In contrast to most Campylopus species, D. thermalis possesses two stereid bands.Ecology and distribution: The species is known from numerous collections (held mostly in MW) on the slope of Baranskogo volcano in Iturup Island , where it grows along the hot stream banks under Sasa understory at altitudinal range of 220\u2013280 m a.s.l. Similar non-sporulating Dicranella plants were frequently encountered in thermal habitats of Kamchatka Peninsula and northern part of Kunashir Island, but they were mostly not collected and therefore their identity remains uncertain.Paratypes : Accession numbers MW9073555-MW9073558, MW9007288-MW9007292, MW9073559.Bryopalisotia Bonfim Santos & Fedosov, gen. nov.\u2013Type: Bryopalisotia filiformis (P. Beauv.) Bonfim Santos & FedosovEtymology: The name was chosen as a tribute to A.M.F.J. Palisot, Baron de Beauvois (1752\u20131820), a French naturalist and author of Prodrome des cinqui\u00e8me et sixi\u00e8me familles de l\u2019\u00c6th\u00e9ogamie, les mousses, les lycopodes , Bory s.n. \u2261 Thysanomitrion filiforme (P. Beauv.) Arn. In M\u00e9m. Soc. Linn. Paris 5: 263. 1827 \u2261 Aongstroemia filiformis (P. Beauv.) Wijk & Margad. in Taxon 9: 50. 1960 = Aongstroemia jamaicensis M\u00fcll. Hal., Bull. Herb. Boissier 5: 554, 1897 fide , Cal. [=California], M.A. Howe.Calcidicranella varia (Hedw.) Bonfim Santos, Fedosov & Jan Ku\u010dera, comb. nov. \u2261 Dicranum varium Hedw. in Sp. Musc. Frond.: 133. 1801\u2013Lectotype: , [Hedwig?] s.n. B\u00e9h\u00e9r\u00e9 in Muscol. Rothom. 29. 1826 \u2261 Aongstroemia varia (Hedw.) M\u00fcll. Hal. in Syn. Musc. Frond. 1: 435. 1848 \u2261 Dicranella varia (Hedw.) Schimp. Coroll. Bryol. Eur. 13: 1856 \u2261 Anisothecium varium (Hedw.) Mitt. in J. Linn. Soc., Bot. 12: 40. 1869.0040364, : Figure Calcidicranella pacifica (W.B. Schofield) Jan Ku\u010dera & Fedosov, comb. nov. \u2261 Dicranella pacifica W.B. Schofield, Bryologist 73: 703, 1970.\u2013Holotype: Canada. British Columbia: Vancouver, Spanish Banks, 49\u00b016\u2032 N, 123\u00b014\u2032 W, seepy silt cliffs and cliff base, Schofield 40,422 (UBC).Calcidicranella obtusifolia (Berggren) Fedosov, Ignatova & Jan Ku\u010dera, comb. et stat. nov. \u2261 Dicranella varia var. obtusifolia Berggren, Kongl. Svenska Vetensk. Acad. Handl., n.s. 13(7): 36. 1875\u2013Type: Musci Spetsbergens. Exsicc. No. 9. Anisothecium varium var. obtusifolium (Berggr.) Podp., Consp. Musc. Eur. 118. 1954.Anisothecium rubrum var. obtusiusculum Lindb. & Arnell, Kongl. Svenska Vetensk. Acad. Handl., 23(10): 85. 1890, syn. nov.\u2013Type: \u2018Fl. Jen., T. subarct., Polovinka fr.\u2019 \u2261 Dicranella varia var. obtusiuscula (Lindb. & Arnell) Paris, Index Bryol. 336. 1896 \u2261 Anisothecium varium var. obtusiusculum (Lindb. & Arnell) Podp., Consp. Musc. Eur. 118. 1954.=Description: Plants small, gregarious, light green or yellowish. Stems simple, ca. 0.1\u20130.2 cm, with strong round central strand and weak sclerodermis, evenly foliated. Leaves appressed, straight or slightly curved when dry, spreading when moist, 1.0\u20131.8(\u20132.2) mm, with wide, ovate bases and more or less distinct shoulders, above shoulders gradually narrowed towards blunt acumen, concave, lower leaves not widened, triangular; margins plane at base, narrowly recurved at shoulders and just above and below them or almost to the leaf tip, unistratose proximally and partly bistratose distally, uneven above, rarely throughout the margin; costae ending just below apices, rarely percurrent, rather strong, occupying ca. 1/7\u20131/5 of leaf base, distinctly delimited from leaf lamina, in transverse section with 2\u20134(\u20135) large ventral guide cells, differentiated dorsal epidermis and single weak stereid band; leaf lamina unistratose with occasional bistratose strands distally; upper leaf cells short rectangular to subquadrate, 12\u201320 \u00d7 7\u201312 \u00b5m, smooth, not bulging, proximally longer and wider, 44\u201390 \u00d7 10\u201317 \u00b5m, elongate-rectangular, 2\u20133 rows of cells along margins narrower, ca. 4\u20136 \u00b5m wide. Dioicous. Perichaetial leaves of the same length, but with wider and longer base, more abruptly narrowed to lanceolate or short subulate acumen. Setae 3\u20135 mm red to brownish. Capsules ca. 1 mm, asymmetric, curved, ovate, with short neck, strumose, brownish-red, distinctly furrowed, red rimmed distally, exothecial cells irregular in shape, thick-walled with equally thickened walls, longer and narrower along furrows, with few stomata proximally. Annulus not differentiated. Operculum conic. Peristome teeth red to brownish, 450\u2013500 \u00b5m long, unequally split for nearly half of their length, longitudinally striolate proximally, papillose distally. Spores 14\u201317 \u00b5m, smooth, yellowish-brown, mature in summer. Rhizoidal tubers not seen.Differentiation: C. obtusifolia resembles C. varia or C. howei in habit but differs in smaller plants with stems up to 5 mm, while stems of C. varia often extend to 1 cm. Leaf margins in C. obtusifolia are plane below shoulders, while C. varia has leaf margins recurved from the basal leaf portion and C. howei has leaf margins recurved mostly in the lower leaf part only, often only on one side. Leaf tips in C. obtusifolia are typically blunt, with costae ending a few cells below tips to being percurrent, while in C. varia/howei leaf tips are sharp and costae excurrent. Capsules of C. obtusifolia are strumose and distinctly longitudinally furrowed, while in C. varia/howei capsules are not strumose, smooth or rarely indistinctly furrowed. Exothecial cells in C. obtusifolia approach C. howei, they are irregular in shape, with equally thickened walls, while in C. varia longitudinal walls of exothecial cells typically are thicker than transverse ones. Although in many formal characters C. obtusifolia resembles North American C. pacifica, the latter species is much larger; moreover, with its contorted to crisped leaves and smooth capsules it is quite distinct from C. obtusifolia.Distribution and ecology: A predominantly Arctic species, described from Svalbard and also known from a single locality in Nenets Autonomous District (European Russia), suite of localities along Yenisey River, in Taimyr Peninsula, Anabar Plateau and from a single locality in Yakutia. According to the protologue of Anisothecium rubrum var. obtusiusculum Glazialt\u00fcmpel am Cerro Incachacca, ca. 4600 m, No. 2599; an Steinen im Bach, oberes Llavetal, ca. 4200 m, No. 4832; in einem Quellbach des Pajonaltales, ca. 4000 m, No. 3264; in einem Quellbach der Cerros de Malaga, ca. 4000 m, No. 4359.Aongstroemia campylophylla (Taylor) M\u00fcll.Hal. in Syn. Musc. Frond. 2: 608. 1851. \u2261 Dicranum campylophyllum Taylor in London J. Bot. 7: 281. 1848\u2013Lectotype (designated in British N. America (probably from the Rocky Mountains) T. Drummond, no 101 in part, (probable holotype NY325565) \u2261 Dicranella canadensis (Mitt.) Austin in Bot. Gaz. 2: 96. 1877 \u2261 Dichodontium canadense (Mitt.) Lesq. & James in Man. Mosses N. America 62. 1884.Dicranella schreberi var. robusta Schimp. ex Braithw. in J. Bot. 9: 289. 1871, syn. nov.\u2013Type: , at various places in Cheshire, at Milnthorpe (Barnes) and near Melnrose .==Anisothecium schreberianum var. elatum (Schimp.) Wijk & Margad. in Taxon 7: 288. 1958, fide In humidis argillaceis Scotiae. Greville, Hooker, Arnott s.n. \u2261 Dicranum grevilleanum (Brid.) Bruch & Schimp. in Bryol. Eur. 1: 123. 54 (fasc. 37-40. Mon. 19. 7.). 1847 \u2261 Dicranella grevilleana (Brid.) Schimp. in Coroll. Bryol. Eur. 13. 1856 \u2261 Anisothecium grevilleanum (Brid.) Arnell & C.E.O. Jensen in Bih. Kongl. Svenska Vetensk.-Akad. Handl. 21 Afd. 3(10): 49. 1896 \u2261 Dicranella schreberi var. grevilleana (Brid.) M\u00f6nk. in Laubm. Eur. 179. 1927.Aongstroemia herrerae (R.S. Williams) Bonfim Santos & Fedosov, comb. nov. \u2261 Hygrodicranum herrerae R.S. Williams in Bryologist 29: 37. pl. 3: f. 1\u20139. 1926 \u2013Type: \u201cGrowing about waterfalls, R\u00edo Tapfi, province of Cuzco, Peru, at 3600 m.\u201d F.L. Herrera No. 792, Sept. 1925, same locality, F.L. Herrera No. 798a\u201d.Aongstroemia hookeri M\u00fcll.Hal., Syn. Musc. Frond. 2: 607. 1851.\u2013Type: Insula Eremitae ad Cap. Horn: J.D. Hooker. \u2261 Anisothecium hookeri Broth., Nat. Pflanzenfam. (ed. 2) 10: 178. 1924. \u2261 Dicranella hookeri Cardot, Bull. Herb. Boissier, s\u00e9r. 2, 6: 4. 1906.Anisothecium perpusillum Dus\u00e9n fide , sin. coll. s.n. Dixon in Rev. Bryol. Lich\u00e9nol. 6: 104. 1934 \u2261 Dicranella schreberiana (Hedw.) Hilf. ex H.A. Crum & L.E. Anderson in Mosses E. N. Amer. 1: 169. 1981 = Bryum crispum Schreber, nom. inval., Spic. Fl. Lips. 79 (no. 1038). 1771 = Dicranum schreberi Sw. nom. illeg., Monthly Rev. 34: 538. 1801.0040018, : Figure 0040018, : Figure Dicranella and Aongstroemia [Pseudoditrichum, Flexitrichum, Scouleria, Drummondia, Hymenoloma, and Bryoxiphium, and we further substantially reduced the representation of Leucobryaceae, Rhabdoweisiaceae, Dicranaceae, and related families , and also Ditrichaceae including Aongstroemia orientalis and A. julacea, which will be treated in a dedicated future article. On the other hand, we added accessions of Dicranella staphylina, D. humilis, D. varia incl. its neglected var. obtusifolia, D. pacifica, D. grevilleana, D. schreberiana incl. its var. robusta, D. campylophylla, D. hookeri, D. heteromalla, D. curvipes, D. polii, D. vaginata, Aongstroemia longipes, A. filiformis, Neodicranella hamulosa, and unassigned dicranelloid plants from Pacific Russia, which were found to be related to Dicranella s.str. and to Diobelonella/Dichodontium/Neodicranella grade. Newly generated trnK\u2013psbA data were added for at least one representative of each major lineage left. Laboratory protocols for isolation of DNA, amplification and sequencing followed the protocols described in [The matrix of molecular data was largely based on that used for the backbone phylogeny of Dicranidae, with a focus on stroemia . With reribed in ,10,56,57http://purl.org/phylo/treebase/phylows/study/TB2:S30163, accessed on 28 January 2023) was tentatively partitioned according to the sequenced regions , rps4\u2013trnS (R), trnK\u2013psbA (K), nad5 (N) with respect to their significantly differing coverage, rather than according to coding and non-coding regions. The best-fit partitioning scheme and models of nucleotide evolution were searched for in PartitionFinder2 [trnF\u2013trnL partition and GTR + I+G for the remaining ones. Indel data were scored for individual partitions using the simple indel coding (SIC) approach [trnT between trnL and rps4 (T) and (b) trnK\u2013psbA (K) data, which were successively added to the working pilot analyses. Given the amount of phylogenetic signal, the K data were also analyzed separately from the 52 accessions for which these data were available.Sequences were aligned using MAFFT v. 7 with thenFinder2 . The resapproach in SeqStapproach and addeapproach , we did Phylogenetic reconstructions were performed using Bayesian inference (BI) and maximum likelihood (ML). BI was run in MrBayes v.3.2.7 in two pIn addition to standard microscopic observations during the revision of herbarium specimens, preparation of taxon descriptions, and illustrations, images of peristomes were obtained by scanning electron microscopy (SEM) with a JSM-6380 (JEOL) at the User Facilities Center of M.V. Lomonosov Moscow State University. Peristomes mounted on stubs were coated with gold without any additional preparation, and light microscope illustrations were made under a stereomicroscope Olympus SZX-7 with a digital camera Infinity 8, with Z-stacking in Helicon Software ."} +{"text": "Arterial wave reflection and aortic valve stenosis: diagnostic challenges and prognostic significance by Pagoulatou S, Adamopoulos D, Rovas G, Bikia V, M\u00fcller H, Giannakopoulos G, Mauler-Wittwer S, Licker M-J, Stergiopulos N and Noble S. (2022) Front. Cardiovasc. Med. 9:863968. doi: 10.3389/fcvm.2022.863968An Erratum on An omission to the funding section of the original article was made in error. The following sentence has been added: \u201cOpen access funding was provided by the University of Geneva\u201d.The original version of this article has been updated."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-023-40223-4, published online 14 August 2023Correction to: The original version of this Article contained errors.In the Author Contributions section,\u201cA.S.T. and S.V.: conceptualization, supervision, investigation, data curation, methodology. R.B., M.H.S., A.S.T. and S.V.: data curation, formal analysis, writing\u2014original draft. M.H.S., M.S.K, G.H.: provided sugarcane commercial hybrids, species clones and resources required for experiments. M.H.S., M.S.K, K.S.R., R.B., P.G., S.A., R.A.K. and V.K.: validation, Writing\u2014review and editing. All authors have read and agreed to the published version of the manuscript.\u201dnow reads:\u201cA.S.T. and S.V.: conceptualization, supervision, investigation, data curation, methodology. R.B. and M.H.S., A.S.T. and S.V.: data curation, formal analysis, writing\u2014original draft. G.H.: provided sugarcane commercial hybrids, species clones and resources required for experiments. M.H.S., M.S.K, K.S.R., R.B., P.G., S.A., R.A.K. and V.K.: validation, Writing\u2014review and editing. All authors have read and agreed to the published version of the manuscript.\u201dIn addition, the Funding section was incomplete.\u201cICAR-Sugarcane Breeding Institute, Coimbatore is a Govt. Institute working under the umbrella of the Indian Council of Agricultural Research, New Delhi. ICAR-SBI is involved in the sugarcane germplasm collections, maintenance, screening for drought/salinity/disease tolerance and its further utilization in breeding programme. The research work has been taken up at the Institute as a regular activity under the mandate of Institute. No extra funding from other sources has been received for conducting the presented work. This study was supported by the Researchers Supporting Project number (RSP2023R347), King Saud University, Riyadh, Saudi Arabia.\u201dnow reads:The research work has been taken up at the Institute as a regular activity under the mandate of Institute. No extra funding from other sources has been received for conducting the presented work. This study was supported by the Researchers Supporting Project number (RSP2023R347), King Saud University, Riyadh, Saudi Arabia for extending funding support for this publication. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u201dThe original Article has been corrected."} +{"text": "This Special Issue (S.I.) focuses on natural products (N.P.s) as an inspiring resource for new bioactive molecules. Biologically active molecules have been discovered due to technological advances in medicinal chemistry and N.P. research . The N.PThis S.I. focuses on the antimicrobial, antioxidant, antiphotoaging, and anti-inflammatory properties of N.P.s. Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, Alternaria alternata\u2014and bacteria\u2014Bacillus sp. and Pseudomonas aeruginosa pyridine derivatives are extracted from various sources; all are described as critical sources of new molecular motifs that are essential in novel drug development strategies ,10. One review presented in this S.I. shows that pyrrole-2-carboxaldehydes show potential for use in various physiological fields, including in the treatment of diabetes mellitus. These molecules can be used in academic, industrial, or medicinal chemistry . In addition, some sources of N.P.s, such as insects, are not ignored in this S.I. Insect-derived N.P.s are unique in their structures and great activities. Furthermore, this type of N.P. is widely used to expand the chemical space. A review presented in this S.I. provides meaningful and valuable relevant information for researchers, promoting the further development of lead compounds .Marine-derived fungi are crucial resources of novel compounds that are widely used by the pharmaceutical industry to expand its compound libraries. In a review in this S.I., 237 diterpenes are summarized. Derived from fungi, the compound with the most significant cytotoxicity is conidiogenone C, and the compound with the most promising antimicrobial activity is, notably, aspewentin D ,14,15. While proteins are essential macronutrients, a review in this S.I. demonstrates that several amino acid\u2013natural compound conjugates have optimal absorption\u2013distribution\u2013metabolism\u2013excretion (ADME) properties that can be further used for conjugating other desirable compounds. Remarkably, a conjugate of piperine and valine revealed a high level of efficiency against amastigotes ,17.Monoterpene pyridine alkaloids (MPTAs) or cyclopenta[c]pyridines have shown potential antibacterial, insecticidal, antiviral, and anti-inflammatory activities. Like other N.P.s, motifs are a vast source of chemical exploration in areas related to therapeutic chemistry=. The further exploration of MTPAs and cyclopenta[c]pyridines in chemical and drug contexts is to be expected .The research articles and reviews presented in this SI offer distinct perspectives regarding some crucial N.P.s. Furthermore, the manuscripts within this S.I. offer a vast amount of N.P. chemical formulas of N.P.s that can be further used computationally or experimentally to create compound libraries the in search for new drugs."} +{"text": "Mycobacterium abscessus was first isolated from gluteal abscesses in a 62-year-old patient who had injured her knee as a child and had a disseminated infection 48 years later. The species M. bolletii, named after the late microbiologist and taxonomist Claude Bollet, was described in 2006. In current taxonomy, M. bolletii and M.massiliense have been incorporated into M. abscessus subsp. bolletii. From the Latin"} +{"text": "The third author's name is misspelled. The correct spelling is Federica Pezzimenti. The correct citation is: Bernardi E, Deflorian G, Pezzimenti F, Diaz VM, Mione M, et al. (2010) Characterization of the Regulatory Region of the Zebrafish Prep1.1 Gene: Analogies to the Promoter of the Human PREP1. PLoS ONE 5(12): e15047. doi:10.1371/journal.pone.0015047"} +{"text": "AbstractBuprestidae; Agrilus bilineatus (Weber), Agrilus crinicornis Horn, Agrilus obsoletoguttatus Gory, Agrilus putillus putillus Say, Brachys ovatus (Weber), Buprestis sulcicollis (LeConte), Chalcophora liberta (Germar), Phaenops aeneola (Melsheimer), and Taphrocerus gracilis (Say) are newly recorded for New Brunswick, Canada. Agrilus bilineatus, A. crinicornis, A. obsoletoguttatus,and B. ovatus are also newly reported for the Maritime provinces. Lindgren 12-funnel traps do not appear to be an effective tool for sampling the Bupresidae. Collection, habitat notes, and distribution maps are presented for each species.Nine species of Buprestidae of North America. This species-rich family of beetles is popular with collectors due to their often bright and metallic coloration. Larvae of many of the wood-boring species bore into roots and logs or within bark or cambium layers of trunks or branches of dead or dying trees and shrubs were dissected to confirm their identity. The genital structures were dehydrated in absolute alcohol and mounted in Canada balsam on celluloid microslides or glued on cards and pinned with the specimens from which they originated.Males of some species of PageBreakDistribution maps, created using ArcMap and ArcGIS, are presented for each species in New Brunswick. Every species is cited with current distribution in Canada and Alaska, using abbreviations for the state, provinces, and territories. New records for New Brunswick are indicated in bold under Distribution in Canada and Alaska. The following abbreviations are used in the text:Acronyms of collections examined or where specimens reside referred to in this study are as follows:AFC Atlantic Forestry Centre, Natural Resources Canada, Canadian Forest Service, Fredericton, New Brunswick, CanadaCNC Canadian National Collection of Insects, Arachnids and Nematodes, Agriculture and Agri-Food Canada, Ottawa, Ontario, CanadaNBM New Brunswick Museum, Saint John, New Brunswick, CanadaRWC Reginald Webster Collection, Charters Settlement, New Brunswick, CanadaAll records below are species newly recorded for New Brunswick, Canada. Species followed by ** are newly recorded from the Maritime provinces of Canada.Buprestidae follows The classification of the Buprestidae are newly recorded for New Brunswick, Canada. Among these, Agrilus bilineatus (Weber), Agrilus crinicornis Horn, Agrilus obsoletoguttatus Gory, and Brachys ovatus (Weber) are also new for the Maritime provinces . Only six specimens of two of the nine species reported here were captured in Lindgren 12-funnel traps during a study to develop a general attractant for the detection of invasive species of Cerambycidae. These traps mimic tree trunks and are often effective for sampling species of Coleoptera that live in microhabitats associated with standing trees . Agrilus planipennis Fairmaire, in Lindgren funnel traps was significantly increased by changing the color from standard black to either purple or green, and by treating the trap surface with Rain-X , a product normally used to reduce friction and water build-up on windshields. It is possible that use of funnel traps with other colors may enhance the catch of other buprestid species.PageBreakNine species of ng trees . HoweverChrysochroini Laporte, 1835Tribe http://species-id.net/wiki/Chalcophora_libertaNew Brunswick, York Co., Fredericton, 16.VIII.1988, G. J. Crain .Pinus resinosa Ait.) and white pine (Pinus strobus L.) (No habitat data were associated with this specimen. Larvae of this species have been reported from red pine (obus L.) .NB, PE http://species-id.net/wiki/Buprestis_sulcicollisNew Brunswick, York Co., 3.5 km S jct. Hwy 3 & 4 near Davis Brook, 11.VI.1998, R. P. Webster, on white pine log ; 15 km W of Tracy off Rt. 645, 45.6837\u00b0N, 66.8809\u00b0W, 10.VI.2007, R. P. Webster, clear-cut (old red pine forest), on red pine stump .Pinus rigida Mill.) and white pine http://species-id.net/wiki/Phaenops_aeneolaNew Brunswick, York Co., 15 km W of Tracy off Rt. 645, 45.6848\u00b0N, 66.8821\u00b0W, 4\u201311.VIII.2009, R. Webster & M.-A. Gigu\u00e8re, old red pine PageBreakforest, Lindgren funnel trap ; same locality and forest type, emgd. 3\u20137.V.2010, C. Hughes, reared from small branches of fallen red pine ; same locality and forest type but 27.VII\u201310.VIII.2010, R. Webster & C. Hughes, Lindgren funnel trap .Pinus virginiana Mill.) (Pinus banksiana), shortleaf pine (Pinus echinata P. Mill.), and spruce (Picea sp.) (Larvae of this species have been reported from red pine and Virginia pine (a Mill.) . Adults cea sp.) . In New NB, PE **http://species-id.net/wiki/Agrilus_bilineatusNew Brunswick, Queens Co., Cranberry Lake P.N.A. 46.1125\u00b0N, 65.6075\u00b0W, 14.VIII.2009, M.-A. Gigu\u00e8re & R. Webster, red oak forest, on foliage of red oak sapling ; same locality data and forest type, 29.VI\u20137.VII.2011, M. Roy & V. Webster, Lindgren forest trap in forest canopy .A. bilineatus have been reported from a variety of Quercus sp., including our native red oak (Quercus rubra L.) (Larvae of ubra L.) . Adults NB . Sunbury Co., Burton near SunpokePageBreak Lake, 45.7658\u00b0N, 66.5546\u00b0W, 20.VI.2007, R. P. Webster, red oak and red maple forest, on foliage of Quercus rubra .Diospyros virginiana L., American beech (Fagus grandifolia Ehrh.), honey locust (Gleditsia triacanthos L.), and white oak occur in the province. Adults from New Brunswick were collected from foliage of Q. rubra, a probable host of A. crinicornis in the province.Larval hosts include alba L.) . Fagus gNB , on red oak, 58-0795 . .A. obsoletoguttatus reported by Ostrya virginiana (Mill.) K. Koch)), and Fagus sp. The specimens from New Brunswick were collected from foliage of red oak during July.Larval hosts of NB .Acer saccharum Marsh.), Norway maple (A. platanoides L.), and honey locust (Fraxinus americana L.), and other hardwood species.Larval hosts include sugar maple **http://species-id.net/wiki/Brachys_ovatusNew Brunswick, Sunbury Co., Burton near Sunpoke Lake, 45.7659\u00b0N, 66.5563\u00b0W, 28.VII.2007, R. P. Webster, margin of red oak stand near lakeshore, on foliage of Quercus rubra .Quercus sp., including red oak http://species-id.net/wiki/Taphrocerus_gracilisNew Brunswick, York Co., Charters Settlement, 45.8428\u00b0N, 66.7279\u00b0W, 20.IV.2005, R. P. Webster, mixed forest, small sedge marsh, in moist grass litter & sphagnum ; same locality and collector but 45.8430\u00b0N, 66.6275\u00b0W, 17.VI.2007, regenerating mixed forest, sweeping foliage of Carex species in small marshy area ; 17 km W of Tracy off Rt. 645, 45.6816\u00b0N, 66.9060\u00b0W, 2.VII.2008, R. P. Webster, red pine forest, marshy area in roadside ditch, sweeping .Rhynchospora corniculata (Lam.)) and bulrush (Schoenoplectus fluviatilis (Torr.)) , and dock (Rumex verticillatus L.). Adults from New Brunswick were collected from Carex sp., swept from foliage in a marshy area in a roadside ditch, and sifted from moist grass litter and sphagnum in a small Carex marsh. Adults were captured during April, June, and July.Larval hosts include beak-rush ((Torr.)) . Althoug(Torr.)) . Adults NB, NS (AB, SK, MB, ON, QC, NB, NS ."} +{"text": "Rhodiola rosea (R. rosea) is grown at high altitudes and northern latitudes. Due to its purported adaptogenic properties, it has been studied for its performance-enhancing capabilities in healthy populations and its therapeutic properties in a number of clinical populations. To systematically review evidence of efficacy and safety of R. rosea for physical and mental fatigue.R. rosea for physical and mental fatigue. Two reviewers independently screened the identified literature, extracted data and assessed risk of bias for included studies.Six electronic databases were searched to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs), evaluating efficacy and safety of R. rosea to be effective as did three of five RCTs evaluating R. rosea for mental fatigue. All of the included studies exhibit either a high risk of bias or have reporting flaws that hinder assessment of their true validity (unclear risk of bias).Of 206 articles identified in the search, 11 met inclusion criteria for this review. Ten were described as RCTs and one as a CCT. Two of six trials examining physical fatigue in healthy populations report R. rosea efficacy is contradictory. While some evidence suggests that the herb may be helpful for enhancing physical performance and alleviating mental fatigue, methodological flaws limit accurate assessment of efficacy. A rigorously-designed well reported RCT that minimizes bias is needed to determine true efficacy of R. rosea for fatigue.Research regarding Rhodiola rosea (R. rosea) is a flowering biennial grown in high latitude and altitude regions of the world. It has been a part of traditional medicine systems in parts of Europe, Asia and Russia for centuries. It has been prescribed for cancer and tuberculosis in Mongolia natural herbal products which are non-toxic in normal doses, produce a non-specific response, and have a normalizing physiologic influence\u201d to deteR. rosea over a 4-week period each experienced a minor and serious headache3. (king's crown or rosenroot or rodia riza or lignum rodium or lignum rhodium or sedum rhodiola or sedum rosea or hong jing tian).mp. 4. 1 or 2 or 35. humans/6. 4 and 51. exp Rhodiola/2. rhodiola rosea.mp.3. roseroot.mp.4. golden root.mp.5. arctic root.mp. 6. king's crown.mp. 7. rhodiola.mp. 8. rosenroot.mp. 9. rodia riza.mp. 10. lignum rhodium.mp. 11. sedum rhodiola.mp. 12. sedum rosea.mp. 13. hong jing tian.mp. IPA14. 4 or 1 or 3 or 7 or 12 or 21. rhodiola.mp. 2. roseroot.mp. 3. golden root.mp. 4. arctic root.mp. 5. king's crown.mp. 6. rosenroot.mp. 7. rosen root.mp. 8. rodia riza.mp. 9. lignum rhodium.mp. 10. sedum rhodiola.mp. 11. sedum rosea.mp. 12. hong jing tian.mp. 13. or/1-1214. limit 13 to human1. exp Rhodiola Extract/or exp Rhodiola/or exp Rhodiola Rosea Extract/2. exp rhodiola rosea/or rhodiola rosea.mp.3. roseroot.mp.4. golden root.mp.5. arctic root.mp.6. king's crown.mp.7. rosenroot.mp. 8. rosen root.mp. 9. rodia riza.mp. 10. lignum rhodium.mp. 11. sedum rhodiola.mp. 12. sedum rosea.mp. 13. hong jing tian.mp. 14. or/1-1315. limit 14 to humanSV receives salary support from Alberta Innovates-Health Solutions. None of the authors have a personal or financial competing interest.All authors read and approved the final manuscript. Author contributions were as follows: SV conceived of the review, LS, CB and SV designed the review, LS, CB and SI conducted the review ; LS analysed dated; SI, LS and CB contributed to the writing of the review; SV provided guidance and supervision and has primary responsibility for final content. All authors critically revised the manuscript for important intellectual content.This project was funded by Canadian Foundation for Innovation (New Initiatives fund 2004/2005), Alberta Value-Added Corporation (AVAC), Alberta Crop Industry Development Fund (ACIDF), Alberta Agriculture and Rural Development (AARD). Funders did not play any role in the concept and design of the study.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/12/70/prepub"} +{"text": "Phlebotomus (nine species) and the genus Sergentomyia (12 species). The following 14 species were reported for the first time in Khash County: P. papatasi, P. bergeroti, P. eleanorae, P. halepensis, P. major, P. mesghali, S. hodgsoni, S. mervynae, S. dreyfussi, S. iranica, S. theodori, S. africana, S. clydei, and S. christophersi. The composition of species in Khash County is similar to other parts of Iran. However, the dominance of P. kazeruni in Khash County may suggest that this species should be considered as a potential vector in the region of Khash.Sand flies (Diptera: Psychodidae: Phlebotominae) are the biological vectors of leishmaniasis all around the world. In 1997, sand flies were collected in 14 cities and villages of Khash County in southeastern Iran, using 848 sticky traps (castor oil-coated white papers 20 \u00d7 30 cm). In this study, a total of 4673 sand flies, with 25.23% females and 74.77% males, were collected and identified to species mainly from mountainous areas. The 21 species of sand flies belonged to the genus Three forms of leishmaniasis including zoonotic cutaneous leishmaniasis, anthroponotic cutaneous leishmaniasis, and visceral leishmaniasis are public health problems in Iran and its neighboring countries such as Afghanistan and Pakistan. Zoonotic cutaneous leishmaniasis is the most abundant and endemic form of the disease in Iran, particularly in the East and Southeast foci. The city of Khash is near Chabahar, Mirjaveh, and Zahedan, which are the South and Southeast leishmaniasis foci in Iran reported 42 species of Phlebotomine sand flies in Iran. More recently, Rassi et al. (P. papatasi is recognized as the main vector of leishmaniasis to humans (Sand flies (Diptera: Psychodidae: Phlebotominae) are the biological vectors of leishmaniasis. The first comprehensive entomological study on sand flies of Iran was done by Mesgali (1960), who reported 12 species belonging to the genus i et al. showed ti et al. . Finallyi et al. have proo humans .The objectives of the present study were to determine sand fly species diversity, relative population abundance, and sex ratio. These data provide basic epidemiologic information for vector population control programs to reduce the incidence of zoonotic cutaneous leishmaniasis in the region.The investigation was carried out in 1997 in Khash County, which is located in Sistan-Baluchistan Province, Southeast Iran . Khash County has a dry climate with a total rainfall of 154 mm per year. Diurnal and seasonal temperature variations range from 44 \u00b0C in summer to 18.40 \u00b0C in winter. The relative humidity ranges from 11.9% in September to 73.4% in January. Khash County has a population of about 130,000 people .Sand fly collections were conducted in 14 cities and villages of Khash County: Khash, Nookabad, Eskalabad, Baluchabad, Sabzgaz, Gezo, Irandegan, Dadkan, Reeis, Pawel, Sangan, Karvandar, Gunich, and Tamin. The sand flies were collected using 848 sticky traps (castor oil-coated 20 \u00d7 30 cm strips of white paper), mainly in mountains and plains areas during the early summer of 1997. The traps were installed after sunset and were collected before the following sunrise. Only one replicate (14 samplings) was performed during the early summer per location because of local problems in the area of the study.Sand flies were removed from the traps, rinsed in acetone, and preserved in 70% ethanol. All specimens were sexed and the head capsule, ventral side facing up, mouth parts and end parts of male and females, including male and female genitalia, were separated. They were placed in Puri's clearing medium for one week, which is sufficient to clear, and were dry mounted on microscope slides, including male terminalia, spermatheca, pharynx armature, and buccal armature. Finally, they were mounted on microscope slides, using Puri's medium . The spePhlebotomus and 12 belonged to the genus Sergentomyia. The results are summarized in Tables 1 and 2. The most abundant species were P. kazeruni and S. tiberiadis, representing 39.3% of Phlebotomus spp. and 62.5% of Sergentomyia spp., respectively. The 21 species that were reported for the first time from Khash County can be seen in Table 3.A total of 4673 sand flies, of which 25.23% were females and 74.77% were males, were collected from the outdoor locations. Of the 21 species of sand flies identified, nine belonged to the genus P. kazeruni, P. sergenti, P. alexandri, P. papatasi, and S. tiberiadis (Table 1). All details of data are presented in the Tables 1 and 2.The sex ratios showed that the traps were more attractive for males, in particular for Phlebotomus and 12 species of Sergentomyia were collected. Phlebotomus kazeruni was the most abundant sand fly species. This result is different from similar surveys that found P. papatasi to be the predominant species. However, the Khash area is a mountainous region and P. kazeruni is mostly found in mountains. Nevertheless, regarding species composition, the results of this study are similar to other studies carried out in nearby areas. The results of Kakarsulemankhel and four species of Sergentomyia , the method of sand fly collections were different. In the current study, the sand flies were collected outdoors with sticky traps from cracks, crevices, and holes of mountains, and in the Arsanjan study the sand flies were collected from rodent nests using sticky traps.Another study carried out in Arsanjan County, south of Iran, collected eight species of clydei) . Among tP. papatasi, P. caucasicus, and S. sintoni, with P. papatasi being the predominant species. The species P. caucasicus was not collected in our survey. Sex ratios for P. papatasi and S. sintoni in Ahmad Abad and Bekran villagesshowed a greater attraction of the traps for females may be Phlebotomus species: P. papatasi, P. major, P. sergenti, P. mongolensis, P. caucasicus, P. keshishiani, P. ansarii, P. longiductus, and P. halepensis, and three Sergentomyia species: S. Sintoni, S. dentata, and S. pawlowskyi. The same species, except P. keshishiani, P. ansarii, P. longiductus, and S. pawlowskyi, were all collected in the present study.In Shahreza County, central Iran, Motovali Emamia and Yazdi collecteP. papatasi, P. sergenti, and P. caucasicus, with P. papatasi being dominant in Abardejeh.In South of Tehran, Iran, Nekouie et al. reportedP. papatasi, P. sergenti, P. caucasicus, P. mongolensis, P. alexandri, P. ansarii, P. major, P. kandelakii, S. sintoni, S. dentata, and S. pawlowskyi, with P. sergenti as the dominant species. The species P. papatasi, P. sergenti, P. alexandri, P. major, S. sintoni, and S. dentata were also reported in our study.In Kuhpayeh district, central Iran, the following species were found in the study of Abdoli et al. : P. papaP. sergenti, P. major, P. alexandri, P. kandelakii, P. tobbi, P. brevis, P.(Adlerius) sp., P. halepensis, S. pawlowskyi, and S. theodori. The absence of P. papatasi in the Qom survey was puzzling , Azni et al. reportedn et al. collectePhlebotomus: P. papatasi, P. major, and P. salehi, and five species from the genus Sergentomyia: S. sintoni, S. theodori, S. clydei, S. tiberiadis, and S. dentata. All these species with the exception of P. salehi were reported in the current study.In Jask, Southern Iran, Azizi and Fekri identifiPhlebotomus: P. papatasi, P. tobbi, and P. sergenti, and seven species of Sergentomyia: S. sintoni, S. theodori, S. clydei, S. dentata, S. palestinensis, S. mervynae, and S. sogdiana (Grassomyia of Sergentomyia. Most of the species found in Shiraz were also found in the current study.In another study in Shiraz, in South Iran, 10 sand flies species were included on the list, three species of sogdiana . The autP. kazeruni, has never been found as the dominant species in any other study. The most abundant species in the other parts of Iran is P. papatasi. The abundance of P. kazeruni is an important finding that may have epidemiological consequences. This variation may be due to several factors such as the attractiveness of the traps, the environment, and the climatic conditions of capture. In addition, the sex ratio not only varies among the different species, but also between the different areas. Finally, the species diversity found in the current study is in an agreement with the results previously found in Chabahar region (The sand flies species reported from Khash County have already been reported from other regions of Iran. However, our results show that the abundance of species varies greatly in the different areas. The most abundant species in the current study, r region , 2011.Phlebotomus and Sergentomyia. However, the dominance of P. kazeruni in Khash County is a new finding and may have epidemiological consequences if this species appears to be a potential vector in the region of Khash (The sand fly species distribution reported by our survey in Khash County is comparable to what was found in other parts of Iran, and included species from the two genera of Khash . Consequ"} +{"text": "Knowles himself attributed the finding of P. knowlesi to 2 colleagues (L.E. Napier and H.G.M. Campbell) at the School of Tropical Medicine and Hygiene in Calcutta who found the protozoan while investigating kala-azar transmission. \u201cKnowing that we should be interested in the strain from a protozoological point of view,\u201d Knowles wrote, \u201c[Napier] handed over the original monkey to my assistant, Dr. B.M. Das Gupta.\u201d Das Gupta maintained the strain in monkeys until he and Knowles were able to carry out human infection experiments, which they reported in 1932.Sources: Centers for Disease Control and Prevention. The history of malaria, an ancient disease [cited 2011 Jul 22]. http://www.cdc.gov/malaria/about/history; Dorland\u2019s illustrated medical dictionary. 31st ed. Philadelphia: Saunders; 2007; Knowles R. Monkey malaria. BMJ. 1935;2:1020. doi:10.1136/bmj.2.3907.1020; Knowles R, Das Gupta BM. A study of monkey-malaria, and its experimental transmission to man. Ind Med Gaz. 1932;67:301\u201321.From the Greek,"} +{"text": "Dis. Model. Mech. 6, 905\u2013914 (2013). There is inappropriate paraphrasing/close copying of five unattributed review papers.There was an error published in The authors agree that they were greatly influenced by the clarity and insight of the excellent reviews listed below and sincerely apologise for omitting to cite them, which was an unintentional mistake.The references are listed below together with a description of the sections in which they should have been cited:Browning, J. D. and Horton, J. D. (2004). Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest. 114, 147\u2013152. Citation missing from section on NASH pathogenesis: a \u2018two-hit\u2019 model.Dowman, J. K., Tomlinson, J. W. and Newsome, P. N. (2010). Pathogenesis of non-alcoholic fatty liver disease. Q. J. Med. 103, 71\u201383. Citation missing from section on NASH pathogenesis: a \u2018two-hit\u2019 model.Nivala, A. M. (2011). Novel therapies for NAFLD. PhD thesis, Colorado State University. Citation missing from section on NASH pathogenesis: a \u2018two-hit\u2019 model.Schlegel, A. (2012). Studying non-alcoholic fatty liver disease with zebrafish: a confluence of optics, genetics, and physiology. Cell. Mol. Life Sci. 69, 3953\u20133961. Citation missing from Introduction and section on Mutant fish models of NAFLD and NASH.Stern, H. M. and Zon, L. I. (2003). Cancer genetics and drug discovery in the zebrafish. Nat. Rev. Cancer3, 533\u2013539. Citation missing from Figure 2 legend.Disease Models & Mechanisms (DMM) recognises the difficulties that non-native writers face in correctly describing other authors\u2019 work, but review articles are expected to provide an original synthesis of and commentary on previously published work: the words should be the authors\u2019 own and all publications from whom they borrow ideas and words should be referenced.In accordance with COPE (Committee on Publication Ethics) guidelines, DMM has carried out a thorough investigation into this matter and believe that the majority of the paper is original and appropriately referenced.http://dmm.biologists.org/site/policies/publishing_ethics.xhtml#origin.DMM is a member of COPE and is committed to maintaining the integrity of the published record and to publishing the most objective and unbiased scientific information possible. As such, DMM takes any claims of plagiarism very seriously and has a duty to its authors, editors and readers to investigate any such concerns. We list our publishing ethics policies clearly on our website and our policy on Originality and Plagiarism can be found at"} +{"text": "AbstractRhyparochromidae and especially Drymini is briefly reviewed. Two new species level synonyms are proposed: Taphropeltus javanus Bergroth, 1916, syn. n. = Taphropeltus australis Bergroth, 1916, syn. n. = Brentiscerus putoni . A monotypic new genus, Malipatiliusgen. n. is established.The history of the taxonomic research of Hemiptera: Heteroptera) and among them the family Rhyparochromidae developed unevenly during the past more than 250 years . Between the first and second World Wars the research intensity decreased globally except of the Nearctic region where important works were published by H. G. Barber and others. In the 1960\u2019s\u20131980\u2019s the research underwent an active period, and a high number of new taxa was described especially from the Afrotropical and Australian (+\u00a0Pacific) Regions, but also from other regions; the activity of J. A. Slater and G. G. E. Scudder, furthermore A. C. Eyles, R. E. Linnavuori, M. Malipatil and T. E. Woodward was especially significant. In the last twenty years the descriptive activity slackened again.The knowledge on the taxonomy of the true bugs . A good characterization of the world distribution of the Drymini (and of the other Rhyparochromidae) was given by The situation in respect of the tribe PageBreakMembers of Drymini are usually moderately vagile. This might partly explain the fact that only a few species are distributed in more than one zoogeographical area. Most of these species occur in China where they center the Oriental areas but more or less broadly extend to the neighbouring Palaearctic territories or vice versa. Therefore the species numbers described from the each region are only slightly lower than the actual number of the species known in the respective areas .Drymini, the following things can be observed . Before World War II the Nearctic species were most intensively studied. The knowledge of the Drymini of the Australian Region was developed extremely thanks to Examining the history of the genus and species description in observed : during PageBreakLygaeus Fabricius, 1794, Pachymerus Lepeletier & Serville, 1825, or Rhyparochromus Hahn, 1826. Fieber proposed six genera in the Palaearctic Drymini. For the coming few decades the European genera were used to accommodate several new extrapalaearctic species; since most species occurring in the Nearctic Region belong to shared genera it was justified in many cases. Bergroth and Distant were the first to describe several extrapalaearctic genera in the beginning of the 20th century. As a result of their activity, the use of the Palaearctic genera became more restricted. Currently several of these have already been transferred to other genera, but some species have remained \u201cforgotten\u201d or are of uncertain status.The species described before the activity of F. X. Fieber were placed in large \u201cgeneral\u201d genera as The aim of this paper is to correct some of these incorrect combinations.Drymini of the following institutions were examined: Natural History Museum, LondonBMNH; Finnish Museum of Natural History, HelsinkiFMNH; Hungarian Natural History Museum, Budapest, HungaryHNHM; Moravian Museum, Brno, Czech RepublicMMBC; National Museum of Natural History , Leiden, the NederlandsRMNH; Natural History Museum, ViennaNHMW; Tirolese Regional Museum (Ferdinandeum), InnsbruckTLMF; Zoological Museum, AmsterdamZMAN, and Natural History Museum, BerlinMFNB.Type and non-type specimens of Drymini are restricted to a single zoogeographical region. Similarly, most of the genera are also restricted to a single region. As an example, Ischnocoris Fieber, 1860, Notochilus Fieber, 1864, Orsillodes Puton, 1884, and Thaumastopus Fieber, 1870 are of exclusively Palaearctic distribution.As it was pointed out before, most species of Hidakacoris Tomokuni, 1998 is currently known only from Japan, but there are some undescribed Oriental species which belong to this genus too.Gastrodes Westwood, 1840, Lamproplax Douglas & Scott, 1868, and Trichodrymus Lindberg, 1927. It is also frequent that an Oriental or pantropical genus has some species inhabiting marginal areas of the Palaearctic Region, most frequently China and Japan. Such genera are Appolonius Distant, 1901, Mizaldus Distant, 1901 , Paradieuches Distant, 1883, Potamiaena Distant, 1910, and Retoka China, 1935.All more widely distributed Palaearctic genera (13) extend to the Oriental region; 7 of them are found only in these two regions. Palaearctic genera containing species extending to Oriental areas are Drymus Fieber, 1860, is a genus centered in the Holarctic but also having some described and a few undescribed Oriental species.PageBreakTaphropeltus is a predominantly Palaearctic genus which currently contains one exotic species, too . The Australian Taphropeltus australis Bergroth, 1916, was originally included in this genus .is genus . Gross , the two species are considered as conspecific.Both Taphropeltus javanus is dated to 12 September 1916, while the article describing Taphropeltus australis was published during October of the same year.Both species were described in 1916. Both of the two journal issues contain explicit information about the date of the publication: the description of Brentiscerus putoni , which is described from New Zealand, with the mentioned species. They are virtually identical. As a conclusion, the following nomenclatural changes are required:Furthermore, I compared the lectotype and additional non-type specimens of http://species-id.net/wiki/Brentiscerus_putoniScolopostethus putoni Buchanan White, 1878: 75. Syntypes : New Zealand; BMNH!Taphropeltus javanussyn. n. Bergroth, 1906a [12 Sep.]: 220. Syntype (s): [Indonesia:] Java, Mt. Tengger; lost? Taphropeltus australissyn. n. Bergroth, 1906b [Oct.]: 13. Syntype (s): Australia: Victoria; lost? PageBreakScolopostethus putoni. Lectotype .Taphropeltus australis and Taphropeltus javanus are probably lost, no references mentioning them could be traced and they could not be found in FMNH where most of Bergroth\u2019s collection is deposited. Taxonomic decisions were made based by examination of non-type specimens from Australia, New Guinea and Indonesia, respectively.The types of INDONESIA. Dammerman / O. Soemba / 700 m 249 / Kananggar / v. 1925 ; Dammerman / Idjen 1850 m / Ongop-ongop / 19. V. 1924 / No. 17 (RMNH); Banjoewangi / JAVA 1909 / MacGillavry ; INDONESIA: centr. Java / Pokalongan Reg., Bandar / 1050 m / 2.1998., leg. S. Jakl ; IDN-Bali Isl. / Bedugul reg. 1300m / Tamblingan lak.N.R. / S. Jakl lg., 3.2005 ; Sunda Exp. Rensch / W.-Flores / Rana M\u00eas\u00e9 / 20.\u201330.6.1927 ; Sumba (E) / Luku-Melolo N. R. / 550 m, VII. 2005 / leg. S. Jakl . PAPUA NEW GUINEA. New Guinea / Mt. Kaindi / 2400 m / 15-16. IV. 1965 // Nr. 34 / Coll. Balogh et / Szent-Iv\u00e1ny ; Austr. New Guinea / Wau 1250 m / 10.-20. XI. 1972 / J. v. d. Vecht ; Museum Leiden / Neth. New Guinea Exp. / Star Range 1260 m / Sibil / 15. VI. 1959 // Taphropeltus 3 (handwriting) ; AUSTRALIA. N.S.W. / Cassilis \u201cKuloo\u201d / Station 710 m / 31\u00b050'9\"S, 150\u00b08'E // 25.X.2000 / Hung. Entom. Exped. / leg. A. Podluss\u00e1ny, G. Hangay & I. Rozner ; N.S.W. / Karai State Forest / Kookaburra, 943 m / 31\u00b01'4\"S, 152\u00b020'2\"E // 27\u201328.X.2000 / Hung. Entom. Exped. / leg. A. Podluss\u00e1ny, G. Hangay & I. Rozner ; N.S.W., Putty / Road, Cases Courvert / 10\u201311.I.2006 leg. G. Hangay, I. Rozner & A. Podluss\u00e1ny ; N.S.W. / Milton, 21.I.2006 / leg. A. Podluss\u00e1ny, G. Hangay & I. Rozner ; New South Wales / J.P. Duffels // Eucalyptus / forest // 48 km N of Singleton / 15 I 1983 . NEW ZEALAND. C. Darwin / 85\u2013119. ; (handwriting): Kaitaia NZ / 1 VIII 23 / JG Myers // Base of prairie grass // (printed): J. G. Myers Coll. B.M. 1937-789. .Brentiscerus putoni in New Zealand possibly originates from Australia, where all congeners are native. There are no autochthonous Drymini species in New Zealand, only some introduced species occur, as Brentiscerus putoni, Grossander major and Paradrymus exilirostris Bergroth, 1916 and Taphropeltus ornatus Linnavuori, 1978. Both of these species are morphologically rather distinct from the type species, Taphropeltus hamulatus Thomson, 1870, and the other known Palaearctic members of the genus. It is sure that at least Taphropeltus ornatus belongs to another genus, as it also was suggested by Eremocoris and Scolopostethus are morphologically very close to each other. Some of the described species and also certain undescribed species from the Afrotropical and Oriental Regions are morphologically transitional between Eremocoris and Scolopostethus. E.g., the African Scolopostethus maumus Scudder, 1962, is apparently very closely related to Eremocoris africanus Slater, 1964. The possible synonymy of them was already suggested by Although the West Palaearctic species of this complex are easy to classify into one of the two genera, Scolopostethus live in all major zoogeographic regions, with many undescribed Oriental species. The Australian Scolopostethus forticornis Gross, 1965, belongs to a different, so far undescribed genus which is described below as new. Each of the African Scolopostethus daulias Linnavuori, 1978 and Scolopostethus kilimandjariensis Scudder, 1962 represent another undescribed genus. Scolopostethus daulias seems to be related with Taphropeltus ornatus Linnavuori, 1978, but their relationship needs further investigation. Scolopostethus kilimandjariensis belongs to a new genus but its description must be done in frames of a comprehensive study on all other Afrotropical members of the Scolopostethus\u2013Eremocoris complex.Species currently placed to urn:lsid:zoobank.org:act:1B42F8DE-6D15-4B14-BE9B-BD02DEAF79FChttp://species-id.net/wiki/MalipatiliusScolopostethus forticornis Gross, 1965, by present designation.Body elongate oval, dull, extensively punctate, dorsally glabrous (glabrous .Head pentagonal, with dense fine punctures. Eyes small, very prominent. Ocelli well developed, located very far from each other, near the eyes. Antenniferous tubercle curved laterally. Antenna very robust, subclavate.PageBreakPronotum without anterior collar, transversal furrow deep, disk densely punctured. Anterior and posterior margins straight, lateral margin concave, explanate but not widened at transversal furrow. Anterior lobe more globose in male, lateral margin partially parallel here. Scutellum elevated at middle. Fore wing. Clavus with 3 regular rows of punctures. Corium evenly and densely punctate, nearly parallel, costal margin only slightly concave subbasally, apical margin straight. Thoracic sternum punctate except submedian parts of mesosternum. Legs robust, fore femur strongly incrassate, especially in male, with two rows of spines and a very large spine in inner row.Abdomen with dense decumbent pilosity, lateral portion of intersegmental suture between sternites IV\u2013V curved anteriorly, not reaching lateral margin and sublateral furrow; trichobothrial pattern as typical in Drymini.The genus is apparently not monotypic, because besides of the type species very probably congeneric specimens were seen at least from Java, Kalimantan and the New Hebrides.PageBreakMalipatilius gen. n. was originally placed into the genus Scolopostethus. The diagnostic characters of the two genera are presented in Scolopostethus species, Scolopostethus ornandus Distant, 1904 is imaged for comparison on Faelicianus Bergroth, 1918, is perhaps the sister genus of Malipatilius gen. n. This genus has a pale wide lateral carina on pronotum, which is broadened PageBreakat transversal impression, therefore the pronotum is evenly convex laterally. The antenna is also slender, much more than even in Scolopostethus. Another known genera of Drymini, e.g. the superficially similar Salaciola Bergroth, 1893, which sometimes has similar colour and explanate pronotal carina, are certainly not closely related.The type species of Etymology. Patronymic, named after and dedicated to Mallik B. Malipatil, recognizing his excellent contributions to various groups of Australian Heteroptera, particularly Rhyparochromidae. Gender masculine."} +{"text": "Tigecycline was the most active agent against Gram-negative pathogens (except P. aeruginosa), with MIC90s ranging from 0.25\u20132 mg/L (16 mg/L for P. aeruginosa). Amikacin and the carbapenems also possessed good activity against many Gram-negative pathogens here. ESBL-positive E. coli increased in prevalence from 2004 to 2011, while ESBL-positive Klebsiella spp., vancomycin-resistant enterococci and MRSA decreased in prevalence. Linezolid, tigecycline and vancomycin susceptibility were very stable over the course of this study, while susceptibility to ampicillin, piperacillin-tazobactam, ceftriaxone and levofloxacin varied over time according to pathogen; minocycline and cefepime susceptibility among several pathogens decreased during this study.The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was initiated in 2004 to longitudinally monitor the activity of the broad-spectrum glycylcycline antimicrobial tigecycline, and a suite of comparator agents, against an array of clinically important bacterial pathogens worldwide. In this report, we examine the activity of tigecycline and comparators against a collection of 13,245 clinical isolates, both Gram-positive , collected from 27 centres in Italy between 2004 and 2011. Susceptibility was established according to Clinical Laboratory Standards Institute guidelines. Tigecycline and linezolid exhibited very good activity against Gram-positive pathogens, with MIC Enterococcus faecium and reduced penicillin non-susceptibility in Streptococcus pneumoniae between 2007 and 2011. There were also stable proportions of methicillin-resistant Staphylococcus aureus (MRSA) (33\u201340%), high-level aminoglycoside-resistant Enterococcus faecalis (36\u201350%) and a sudden increase of carbapenem-resistant Klebsiella pneumoniae (from 1% in 2006 to 27% in 2011) in Italy during this time.The resistance of Gram-negative and Gram-positive organisms to antimicrobial agents has been widely documented in Europe. The recent report of the European Centre for Disease Prevention and Control (ECDC) included data from 35 Italian hospitals, most of whom used the Clinical and Standards Institute (CLSI) guidelines , and it in vitro and in vivo [Among the different surveillance studies run globally, the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), which has been ongoing since 2004, was initiated to monitor continuously the antibacterial activity of tigecycline and to compare its potency with those of other antimicrobials used in therapy. Tigecycline is the first member of the glycylcycline family of antimicrobials to be administered for bacterial infections. This agent has demonstrated activity against key resistant Gram-negative and Gram-positive phenotypes, both Acinetobacter spp., 25 Enterobacter spp., 25 Escherichia coli, 15 Haemophilus influenzae, 25 Klebsiella spp. (K. oxytoca and K. pneumoniae), 20 Pseudomonas aeruginosa, and 10 Serratia spp. All isolates were drawn from samples collected for diagnosis purposes. Isolates of Enterobacter spp., E. coli and Klebsiella spp. were tested for extended-spectrum \u03b2-lactamase (ESBL) production. Isolates of H. influenzae were tested for \u03b2-lactamase (BL) production. Each centre in Italy was also obliged to collect a minimum of 65 Gram-positive isolates, consisting of 15 Enterococcus spp. , 25 S. aureus, 10 Streptococcus agalactiae, and 15 S. pneumoniae. All body sites were accepted sources of clinical isolates, however, no more than 25% of isolates could be urinary. Only one isolate from each patient could be included in the study, and the participant\u2019s medical history, antimicrobial use, age and gender were not considered.A total of 27 centres in Italy collected isolates for T.E.S.T. between 2004 and 2011 . A minimum of 135 Gram-negative isolates were required to be submitted by each centre, including 15 \u00ae panels or Sensititre\u00ae plates , both of which are compatible with CLSI methodology [\u00ae plates containing imipenem, their use was discontinued in 2006 in favour of Sensititre\u00ae plates containing meropenem.Each participating T.E.S.T. centre was responsible for the initial identification and susceptibility testing of all isolates collected. The minimum inhibitory concentrations (MICs) for each T.E.S.T. agent and pathogen were determined using CLSI broth microdilution methodology and eithhodology . The antA. baumannii and P. aeruginosa were also tested against ceftazidime (CAZ). Gram-positive isolates were tested against linezolid (LZD), penicillin (PEN) and vancomycin (VAN) in addition to the core panel of agents. As well as these, S. pneumoniae isolates were tested against the macrolides plus clindamycin (CLI). The following quality control Gram-negative and Gram-positive strains were tested on each day of isolate testing: E. coli ATCC 25922, H. influenzae ATCC 49247 and ATCC 49766, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212, S. aureus ATCC 29213, and S. pneumoniae ATCC 49619. MIC90 data were included in this manuscript only if the daily quality control (QC) test results were within the acceptable range published by the CLSI [Gram-negative pathogens were tested against the core T.E.S.T. agents, plus amikacin (AMK) and cefepime (FEP). Isolates of After identification and determination of antimicrobial MICs at each T.E.S.T. centre, isolates were sent to a central laboratory, Laboratories International for Microbiology Studies, which is a division of International Health Management Associates, Inc. . The central laboratory organised the transport of isolates from all centres, as well as the storage of isolates. IHMA also performed QC checks on approximately 10% of isolates, which included verification of identification as well as susceptibility testing.Enterobacter spp., the carbapenem breakpoints were revised in 2010 [Acinetobacter and Pseudomonas are not among the organisms listed under the approved clinical indications in the tigecycline prescribing information, no tigecycline breakpoints are available for these organisms [P. aeruginosa and A. baumannii; in the current study, as in previous T.E.S.T. reports, MDR is defined as resistance to three or more classes of agents on the T.E.S.T. panel. The class definitions and corresponding agents used in this analysis were aminoglycosides (amikacin), \u03b2-lactams , carbapenems (imipenem or meropenem), fluoroquinolones (levofloxacin), and tetracyclines (minocycline). Intermediate resistant isolates were not included in the resistant category in this report.Antimicrobial susceptibility was reported using CLSI breakpoints . For Ent in 2010 . For tig in 2010 . As Acinrganisms . Multidrrganisms ,9,10, paA total of 13,245 isolates were submitted from Italian medical centres for T.E.S.T. between 2004 and 2011. Of these, 9,167 (69.2%) isolates were Gram-negative and 4,07E. coli (21.1%), followed by Enterobacter spp. (18.9%), P. aeruginosa (16.0%), K. pneumoniae (15.2%), A. baumannii (9.6%), H. influenzae (8.1%), S. marcescens (7.1%), and K. oxytoca to most of the remaining T.E.S.T. panel agents: amikacin, cefepime, ceftazidime, ceftriaxone, levofloxacin, meropenem and piperacillin-tazobactam. The susceptibility of isolates to amikacin, cefepime, ceftazidime, ceftriaxone and levofloxacin all increased in 2005 before declining again from 2006 to 2011. From 2006 onwards, there was an overall increase in the resistance of A. baumannii isolates to amikacin, cefepime, ceftazidime, ceftriaxone, levofloxacin, and piperacillin-tazobactam (A. baumannii isolates (<1%) were resistant to minocycline between 2004 and 2007, but this percentage rose to 7.9% and 7.6%, respectively, in 2009 and 2010 before decreasing to 2.5% in 2011. A total of 526 MDR A. baumannii isolates were collected in Italy during T.E.S.T. . Among A. baumannii, 79.7% were susceptible to imipenem , but were notably higher between 2008 and 2011 in this study to all T.E.S.T. agents for which breakpoints were available (90 8 mg/L). The resistance of H. influenzae to ampicillin fluctuated during T.E.S.T., ranging from 2.6% in 2009 to 15.0% in 2010. The frequency of \u03b2-lactamase-producing H. influenzae peaked in Italy in 2005 (15.5%), and was lowest in 2009 and 2008 (12.3%), but was low (<5%) in all other years, giving an overall value of 5.0% (K. oxytoca (K. oxytoca isolates were susceptible to imipenem (2004\u20132006) .K. pneumoniae were less susceptible than K. oxytoca to most agents, apart from tigecycline for which 95.8% susceptibility was noted over all years to 35.1% (2004), giving an overall value of 24.1% from 2004\u20132011 (K. pneumoniae were tigecycline (92.9% susceptible) and meropenem (81.2%) . Among aand 2006 while 86and 2006 .P. aeruginosa had lower susceptibility than other Gram-negative pathogens to most T.E.S.T. agents (P. aeruginosa isolates showed the highest levels of resistance to levofloxacin (39.1%) and the lowest levels to amikacin (6.6%) over all T.E.S.T. years. Breakpoints were not available for tigecycline and the activity of this agent was low against P. aeruginosa . Two hundred and eighty MDR P. aeruginosa isolates were collected in Italy over all years of surveillance to cefepime, ceftazidime, levofloxacin, meropenem and piperacillin-tazobactam; the lowest level of resistance was for amikacin (27.1%). A resistance rate of 25.1% to imipenem was reported among all P. aeruginosa; 100% of MDR P. aeruginosa isolates were resistant to imipenem . Ceftriaxone susceptibility was lowest in 2004 (64.3%) and peaked at 94.0% in 2007. Imipenem susceptibility was observed among 85.7% of S. marcescens isolates , E. faecalis (18.1%), S. pneumoniae (16.5%), S. agalactiae (15.0%) and E. faecium , after which time the proportions of resistant isolates decreased, down to 0% in 2011 and most resistant (83.0%) to levofloxacin. Resistance to ampicillin, penicillin and vancomycin increased from 2004 to 2006 to a maximum of 90.0%, 92.5% and 47.5%, respectively. From 2006 onwards, however, resistance to these three antimicrobials decreased, giving overall resistance values of 79.8%, 70.5% and 16.4%, respectively. The frequency of vancomycin-resistant isolates of E. faecium increased from 18.2% in 2004 to a maximum of 47.5% in 2006 but then decreased to 0.0% in 2011 in every T.E.S.T. year . Methicillin resistance was noted in 33.8% of isolates overall, with the annual frequencies of MRSA ranging from 27.8% in 2007 to 45.1% in 2004 . Susceptibility to minocycline decreased from approximately 70\u201375% in 2004\u20132007 to between 26.7% and 55.2% annually over the period 2008 to 2011. Penicillin susceptibility ranged from 67.4% to 80.0% between 2004 and 2011. Azithromycin, clarithromycin and erythromycin had similar overall susceptibility (56\u201357%) and resistance (42.5\u201343.5%) values for S. pneumoniae (S. pneumoniae was more susceptible (67%) and less resistant (32.9%) to clindamycin than to the macrolides between 2004\u20132011. Penicillin-resistant S. pneumoniae (PRSP) increased in prevalence from 4.9% in 2004 to 14.1% in 2010, but decreased to 3.4% in 2011 (S. pneumoniae isolates (2004\u20132006) .et al. [Tigecycline is licensed in Italy to treat complicated intra-abdominal and skin and soft tissue infections. Good clinical results for tigecycline have been demonstrated previously: for example, Bassetti et al. showed aA. baumannii and P. aeruginosa. Against A. baumannii, tigecycline had the lowest overall MIC90 (2 mg/L) of all T.E.S.T. agents in Italy. A previously published Italian surveillance study comprising nine hospitals also determined an MIC90 of 2 mg/L for tigecycline against A. baumannii isolates collected between 2003 and 2004 [A. baumannii isolates had low (\u226451%) susceptibility to amikacin, cefepime, ceftazidime, meropenem and piperacillin-tazobactam. The proportion of A. baumannii resistant to piperacillin-tazobactam in the 2003\u20132004 study (44%) was lower than to the overall value in this T.E.S.T. paper . However, the 2003\u20132004 frequency of imipenem-resistant isolates (50%) was around 36% higher than T.E.S.T. . Both studies used CLSI methodologies to determine imipenem susceptibility, but there were 27 countrywide centres collecting isolates for T.E.S.T., compared with nine centres in the central-south region of Italy for the 2003\u20132004 study. The high incidence of imipenem resistance in the one-year study could, therefore, be due to a localised outbreak of imipenem-resistant A. baumannii infections in this region of Italy during 2003\u20132004. A. baumannii gained resistance to most antimicrobials on the panel over the course of the T.E.S.T. study in Italy as described in this report, and the greatest increase in resistance was to piperacillin-tazobactam (49.1% from 2004 to 2011). There were also >40% increases in resistance to amikacin and levofloxacin.The two Gram-negative organisms in this study for which tigecycline breakpoints were not available were and 2004 . As in tA. baumannii in Italy have focussed mostly on carbapenem-resistant or MDR isolates. Lambiase et al. [A. baumannii isolates from an ICU in Naples between 2007 and 2010, and found that all isolates were MDR, including carbapenems; these isolates were clonal in nature, all possessing the blaOXA-51-like and blaOXA-58-like genes. D\u2019Arezzo et al. [A. baumannii isolates, associated with blaOXA-58-like (22.8%) or blaOXA-51-like (71.1%) genes. Most of these isolates (95.6%) were related to international clonal lineage II. In a study of six hospitals in Florence, Donnarumma et al. [A. baumannii, A1, A2 and A3; A1 was genetically related to the European EU II clone. All isolates possesses the blaOXA-51-like gene, and 65% of these isolates were resistant to imipenem. As reported globally [A. baumannii isolates in Italy, although there may be variation between different geographical areas.Epidemiological studies of e et al. examinedo et al. reporteda et al. showed tglobally , clonal et al. [A. baumannii isolates tested were resistant to three antimicrobial classes . This was only slightly lower than the proportion of MDR A. baumannii collected over the T.E.S.T. surveillance period in Italy (60%). In a separate study of seven centres in Rome carried out from 2004 to 2005, antimicrobial susceptibility was determined for 22 MDR A. baumannii patient isolates [A. baumannii isolates collected in T.E.S.T. were highly resistant to levofloxacin (98.1%), piperacillin-tazobactam (93.7%) and amikacin (87.5%) over all years of surveillance. In the seven-centre study by Principe et al. [A. baumannii isolates (13.6%) were resistant to tigecycline . A single Italian hospital also determined drug resistance among 50 MDR A. baumannii isolates collected between 2008 and 2009 [A. baumannii isolates were resistant to tigecycline . All isolates, however, were 100% resistant to imipenem, levofloxacin and piperacillin-tazobactam, and more than 90% resistant to amikacin, cefepime and ceftazidime. In this T.E.S.T. study, MDR A. baumannii isolates were highly resistant (>79%) to the same antimicrobials, excluding imipenem (38.8%) and minocycline (5.1%).In the 2003\u20132004 Italian study by Mezzatesta et al. , 49.5% oisolates . Of these et al. , three Mand 2009 . Only 4%A. baumannii, a lower overall proportion of MDR P. aeruginosa (19.1%) was recorded in Italy during T.E.S.T. In 2010, a similar percentage of invasive P. aeruginosa isolates from Italy (20.8%) was reported to have resistance to three or more antibiotic classes among aminoglycosides, carbapenems, ceftazidime, fluoroquinolones, and piperacillin-tazobactam [Compared with ruginosa .1% was rE. coli (24.8% from 2004\u20132011). This is a dramatic increase compared to the 10.8% occurrence of ESBL-positive E. coli isolates nationally in 1999 [E. coli as ESBL producers [E. coli [The highest proportion of resistant Gram-negative pathogens in the current Italian study was observed among ESBL-producing roducers . A more solates) . These dE. coli to ceftriaxone in Italy increased more than two-fold between 2007 and 2008, during which time the prevalence of ESBL-producing E. coli isolates almost doubled. In 2010, the ECDC annual report found that in one Italian centre, all 23 of the invasive E. coli isolates resistant to third-generation cephalosporins were ESBL-producers [E. coli bloodstream infections [E. coli resistance in Italy is increasing, possibly due to the spread of ESBL-positive strains.ESBL production has been linked with third-generation cephalosporin resistance . The T.Eroducers . In a 20fections . These fK. pneumoniae were also measured during T.E.S.T. . ESBL production has been associated with reduced carbapenem susceptibility in K. pneumoniae due to a loss of bacterial membrane permeability in some ESBL-producing isolates [K. pneumoniae, from 1% in 2006 to 27% in 2011 [K. pneumoniae, from 2.2% to 19.4% between 2009 and 2012, respectively [K. pneumoniae resistance to meropenem increased in Italy from 1.4% in 2006 to 14.4% in 2011.High proportions of ESBL-producing isolates . The recectively . These rE. faecium, for example, showed 79.8% resistance to ampicillin over all years of Italian surveillance. Similarly, an earlier report documented 70% ampicillin resistance among 913 E. faecium isolates from 20 Italian centres between 1993 and 1995 [E. faecium (7.5%-18.5% susceptibility in 175 isolates from 2004\u20132007). Vancomycin resistance in E. faecium, however, appears to be declining in Italy, as the ECDC reported 21% vancomycin-resistant isolates in 2004 but 4% in 2010 [E. faecium may be related to increased use of infection-control strategies in hospitals, which have been shown to reduce the incidence of vancomycin-resistant enterococci [Although Gram-positive organisms were wholly susceptible to tigecycline, certain pathogens had low susceptibility to other antimicrobials during this T.E.S.T. study. and 1995 . The morand 1995 also fouerococci .S. aureus isolates in Italy were resistant to methicillin, increasing in prevalence between 2007 (27.8%) and 2011 (32.9%) . Similarly, the ECDC reported a small increase in the proportion of MRSA between 2007 and 2010, from 33% to 37% [The current T.E.S.T. data showed that 33.8% of % to 37% . The dis% to 37% , while i% to 37% . An exam% to 37% . Italy tand 2011 .9% through the T.E.S.T. study in 2004\u20132011. Vancomycin \u201cMIC creep\u201d appears to be a regional occurrence and not yet a generalized trend; medical institutions should thus regularly monitor local vancomycin susceptibility among MRSA isolates [S. aureus (and MRSA) in the current study, with 100% susceptibility reported over all study years. Linezolid has previously been shown to be active against vancomycin-intermediate isolates of MRSA collected in Italy, so is an important clinical tool in the fight against resistant infections [Two key antimicrobials in the treatment of infections caused by MRSA are vancomycin and linezolid. There have been numerous reports of increasing non-susceptibility to vancomycin among MRSA isolates in recent years . Howeverisolates . Similarfections .A. baumannii resistance to most antimicrobial agents is higher in Italy by approximately 15%, with the exceptions of amikacin and levofloxacin as well as imipenem and minocycline (resistance is similar). E. coli resistance is also high in Italy: ampicillin and cefepime resistance are around 7% higher, while ceftriaxone and levofloxacin resistance are approximately 12% higher than globally. Among Enterobacter spp., resistance was roughly 10% higher in Italy to ceftriaxone, levofloxacin and piperacillin-tazobactam. Amoxicillin-clavulanate, cefepime, ceftriaxone, levofloxacin and piperacillin-tazobactam resistance among Italian isolates of K. pneumoniae are approximately 6\u20138% higher than isolates globally. Resistance is roughly 6\u201310% higher among isolates of P. aeruginosa from Italy to all antimicrobial agents . Among S. pneumoniae, macrolide, minocycline and clindamycin resistance are about 10%, 12% and 14% higher in Italy, respectively, while penicillin resistance is approximately 7% lower than the global average. Implementation of and strict adherence to resistance control measures, such as ongoing resistance surveillance, improved hand hygiene/increased glove use and/or the use of antimicrobial stewardship programs [Some important differences are observed when resistance rates in Italy are compared to global rates, as reported in Pfizer\u2019s online T.E.S.T. database . In geneprograms ,38, woulThe T.E.S.T. study, like all surveillance studies, suffers from inherent limitations. Although several centres participated in the T.E.S.T. study in Italy over 2004\u20132011, some contributed isolates over several years while others participated in a few years or even just one, causing fluctuations in isolate contribution both geographically and over time. Thus, regional variations in resistance in a given study year may have had a disproportionate influence on apparent national resistance levels.H. influenzae, ESBL-producing K. oxytoca, vancomycin-resistant E. faecalis and PRSP were \u226411.4% in Italy. Another encouraging result of this study was the identification of no vancomycin-resistant Enterococci in Italy in 2011. The above findings may indicate that these drug-resistant organisms are becoming less prevalent in Italian hospitals, and therefore, less of a threat to the welfare of patients. Other pathogens in Italy, including E. coli and K. pneumoniae, have shown increased resistance in recent years, due largely to the spread of ESBL-positive strains. Thus, these organisms must continue to be monitored for further changes in susceptibility in the future. The results of surveillance studies such as T.E.S.T. help members of the healthcare industry to monitor rates of in vitro susceptibility among important pathogens to widely used antimicrobial agents, both globally and regionally.Over all T.E.S.T. years, rates of \u03b2-lactamase-producing 90s ranging from 0.06 to 0.25 mg/L and 1\u20134 mg/L, respectively. Vancomycin and the carbapenems also showed good activity against select Gram-positive pathogens. Tigecycline was the most active agent against Gram-negative pathogens (with the exception of P. aeruginosa), with MIC90s between 0.25 and 2 mg/L (but 16 mg/L for P. aeruginosa), while amikacin and the carbapenems also possessed good activity against many Gram-negative pathogens. Linezolid, tigecycline and vancomycin susceptibility were stable over the course of this study, but ampicillin, piperacillin-tazobactam, ceftriaxone and levofloxacin susceptibility varied by pathogen; minocycline and cefepime susceptibility decreased among several pathogens. ESBL-positive E. coli increased while ESBL-positive Klebsiella spp., vancomycin-resistant enterococci and MRSA decreased in prevalence during this study.Tigecycline and linezolid exhibited very good activity against Gram-positive pathogens in Italy, with MIC"} +{"text": "The second and fifth authors' names were spelled incorrectly. The correct name for the second author is Liza A. McConnell, and the correct name for the fifth author is Ronald L. Koder. The correct citation is: Punnoose A, McConnell LA, Liu W, Mutter AC, Koder RL (2012) Fundamental Limits on Wavelength, Efficiency and Yield of the Charge Separation Triad. PLoS ONE 7(6): e36065. doi:10.1371/journal.pone.0036065"} +{"text": "Itsummarizes the numerous responses of cells with an osteoblastic phenotype and osteogenicprecursor cells and especially their responses to the alteration of their mechanic orgravitational surroundings. The review also discusses the osteogenic cell\u2019s pathways ofsignal transduction and the mechanisms of gravitational sensitivity. It was shown that theearliest multipotent stromal precursor cells of an adult organism\u2019s bone marrow can sensechanges of intensity in a gravitational or mechanic field in model conditions, which may play acertain role in the development of osteopenia in microgravity.This report is a detailed review of the current data on the mechanic and gravitationalsensitivity of osteoblasts and osteogenic precursor cells During the evolution, the skeletal system of land vertebrates adapted itself to an environmentin which one of the most prominent and constant factors is gravity. This factor has determinedthe morphogenesis and structure of all land animals. Certain elements of the skeleton haveevolved for maintaining posture and achieving active locomotion and thus are constantlyexperiencing static and dynamic strain as a result of \u201cdefying the gravitationalforce.\u201d Since humans have started exploring the outer space, the effect of microgravityon the skeletal system has become an important issue, as a lack of mechanic stress can lead to the loss of bone masscaused by insufficient mechanic impulses and gravity\u2013induced deformations, which are notcapable of supporting the integrity of the skeletal remodeling processes , 2.Studies conducted in the last decade have conclusively demonstrated that cultured cells ofosteoblast phenotype are sensitive to microgravity \u20138. Howevth century by A.Y. Friedenstein andhis collegues. Later, MMSC were found and extracted from human bone marrow. A large number ofstudies showed that in vitro MMSC can differentiate into the cellularelements of bone, cartilage and fatty tissues, as well as support and regulate hematopoiesis[During post\u2013natal development the main source of precursor cells is the bone marrow,which is closely connected with bone tissue both in formation and in functioning. Among thenumerous components of the bone marrow stroma, there is a minor population of cells which islocalized in the perivascular region of the marrow but differs from endothelial or smoothmuscle cell populations by the expression of several surface antigens and by the cell\u2019sability to differentiate into tissue cells of mesenchymal origin. So these cells posses all thecharacterstics of multipotent mesenchymal stem/stromal cells (MMSC) , 10. MMSopoiesis\u201313. Itiopoiesis, 15, how in vitro experiments, with thechanges that take place in a human organism under the influence of microgravity, provides anopportunity to differentiate and establish the role of cellular reactions in formingphysiological responses, since it allows to factor out the effects of the integral regulatingsystems of the human organism. The development of the views on cellular gravitationalsensitivity per se can be seen in a series of reports [ in vitro single cell or a cell population can sense changes in thegravitational field are still very heated. Despite this, an enormous body of experimental dataundoubtedly indicates that several types of cultured cells are sensitive to gravity. Inparticular, it was demonstrated that microgravity causes multiple and often reversiblemorpho\u2013functional alterations, including remodeling of the cytoskeleton, change of geneexpression and a mosaic rearrangement of the intracellular regulatory machinery. Thesealterations are reviewed in detail in [Comparison of the results obtained in reports \u201320. Discetail in , 21, 22.It seems that undifferentiated mammalian cells do indeed have structural elements that mayplay the role of \u201cgravitational sensor\u201d and \u201csense\u201d the intensity of amechanical tension, and that many intracellular processes can depend on the value of thegravitational force. The most probable candidates for the role of these structures are variouselements of the cytoskeleton, the nucleus, intracellular organelles and also certain cellsurface receptors (integrins), which interact both with cytoskeletal structures and theextracellular matrix. These structures are able to sense strains and deformations in the matrixwhich are caused either by a gravitational or mechanical field and transfer this signal tointracellular messengers, which then cause a cellular response to the gravity changes , 23, 24.For a long time, osteocytes and the mature inactive osteoblasts were widely accepted to be themost likely candidates for a mechanosensor in the bone tissue , 15. It 2, PGI2), which were involved in the increase of theintracellular calcium concentration, in the activation of the inositol\u20133\u2013phosphatesignal cascade [ in situ bonetissue, as well as by the differences in their maturity and their functions.It was demonstrated on bone cell cultures that certain types of mechanic stimulation, such aspulsatile fluid flow or mechanic strain, can trigger a cascade of regulatory reactions. Thelatter included a transient increase in the production of low molecular weight messengers, suchas NO, expression of the inducible prostaglandin synthase (Cox\u20132) and secretion ofporstaglandins , but more likely by a change in the signaltransduction system caused by microgravity , 40. ThiThe question of whether the immunophenotype of precursor cells remains intact under conditionsof altered gravity may be of much importance for several reasons. First, the mainCD\u2013clusters, which are expressed on the MMSC membrane, regulate various aspects ofprecursor cell functioning. Since they are surface receptors for growth factors and thusmediate the interactions between MMSC and hemopoetic precursors and lymphocytes, they modulatethe maturation and activity of the latter and take part in the interaction of cells withmolecules of the extracellular matrix , 13, 44.Perhaps the most interesting aspect of the biological peculiarities related to osteogenicprecursor cell immunophenotype is the potential role of certain antigens in the mechanisms ofmechanic and gravitational sensitivity. The mechanochemical hypothesis proposes that integrinsand other receptors on the cell surface play an important role in the physical interactionbetween the extracellular matrix and the cytoskeleton and in sensing gravitational signals, 24. Ac \u03b2 1\u2013integrin gene introduced into their genome. Adult mice at2 months of age exhibited an osteopenic phenotype, displayed a characteristic decrease in thebone tissue mass of the hind limbs, and also decreased durability and robustness of the tissue,despite a normal level of bone remodeling [ OPN gene exhibit resistance to unloading by tail\u2013suspension and loseless bone tissue mass than the wild\u2013type mice. Bone marrow MMSC from suspended OPN \u2013negative mice, cultivated ex vivo , are characterizedby a normal ability to form mineralized nodules, as compared to decreased mineralization incultures extracted from wild\u2013type mice after they were suspended [The potential role of several mentioned antigens in the response of bone cells to a rapiddecrease in the mechanical stress level is very intriguing. Proof of the fact that integrins play a role in osteoblast mechanical signalsensitivity was obtained in a study conducted on mice, which expressed \u03b2 1\u2013integrinin the normal amount, and transgenic animals, which had a dominant negative modeling . Anothermodeling . Recent modeling . Mice lauspended . In connuspended .It is known that CD44 plays a role in binding and regulating matrix metalloproteinases (MPPs). MMSC exStudies that focus on the various parameters of collagen biosynthesis of the so\u2013calledmechanocytes (fore mostly fibroblasts and bone cells) under conditions of elevated or decreasedgravity are of especial interest. Hypergravity usually results in increased type I collagenbiosynthesis , while mMAPKphosphorylation, as opposed to p38MAPK phosphorylation levels, which were elevated[A correlation has been found between the level of collagen synthesis and the activation ofMAPK\u2013family kinases, and ERK1/2 in particular, since inhibition of this signaling pathwaycaused decreased gene expression levels and decreased protein production levels of one of thechains of type I collagen . MMSC ceelevated, 49.It was shown that during the course of induced osteogenesis in normal cells of osteoblasticphenotype the activation of type I collagen expression begins after 5\u20136 days of cellcultivation in osteogenic medium, and the peak of protein expression was usually reached ondays 9\u201314, which was the end of the proliferative phase and the beginning of theso\u2013called matrix maturation period . Thisin osteocalcin incells under micrigravity is often accompanied by lowered expression of a key transcriptionfactor, which regulates osteogenic differentiation of osteogenic cells. This factor is Runx2(runt\u2013related transcription factor 2), and it may be one of the primary \u201ctargets\u201dof microgravitational effects on the osteoblastic phenotype.Another important aspect of the effects of microgravity on osteogenic cell differentiation isthe decrease of expression and activity levels of the alkaline phosphatase (APL), and theexpression inhibition of the late mineralized bone matrix marker proteins, such as osteopontinand osteocalcin, which indicate slowing effects on both the early and the late phases ofosteogenic precursor cells\u2019 differentiation into osteoblasts , 55, 58.Runx2 led to the osteogenic differentiation of non\u2013osteogenic cells [Runx2/PEBP2aA/Cbfa1, the main regulator of mesenchymal cell osteogenic differentiation, whichcan respond to the effect of osteogenic growth factors, was first identified in the course ofstudies connected with osteogenic differentiation of pluripotent mesenchymalprecursor\u2013cells of the C2C12 mouse line .Full\u2013flic cells . BMP\u20132, Runx2 \u0438 Smad5 expression, and this effect is later followed byincreases of the expression of genes needed for the formation and maturation of the matrix: ALP, COL1a1 and OC, OPN [ Runx2 being one of them[ Runx2 [ in vivo models alsoshowed that deactivation or lowering of the expression level of Runx2 wereamong the main mechanisms by which hypokinesia affected the osteoblastic phenotype. Partial Runx2 heterozygous knockout mice were particularly sensitive to unloading,which provoked a more noticeable loss of bone tissue mass than in wild\u2013type mice with anormal level of Runx2 expression [It is currently accepted that Runx2 is an essential, but not the only, needed, osteogenesistranscription factor. It cooperates in the postnatal development of osteoblasts with othertranscription factors and also plays a key role in the regulation ofosteogenic differentiation of mesenchymal cells ,65. PreOC, OPN . \u201cMechan of them. It was [ Runx2 . Notablypression .The organism possess a highly surprising connection between osteogenesis and adipogenesis,which is preserved in the cultured precursor cells as well. Probably, these unusual reciprocalinteractions between the two differentiation lineages of MMSC are determined by sharedsignaling pathways and regulating mechanisms, which prioritize the development of onedifferentiation path at the expense the other one, basing this choice on the signals receivedby the cells. At least some of these mechanisms have recently been elucidated. Runx2 \u0438 Dlx5 , and also decreased production of collagen and osteocalcin [PPAR \u03b3 2 is a key adipogenic transcription factor and it functions asa negative dominant regulator of osteogenesis .Specifieocalcin . C/EBP \u03b1 and PPAR \u03b3 2 expression and activating theexpression of osteogenetic transcription factors Runx2, Dlx5 and Osterix [ Sfrp2 and Wisp2, which may indicate,albeit indirectly, the activation of an adipogenic program under microgravity [ ex vivo exhibited lowered levels of cbfa1/Runx2 expression during the activation of osteogenic differentiation.On the other hand, these cells demonstrated an increased expression of PPAR \u03b3 2 during activation of adipogenic differentiationand generally differentiated more easily into the adipogenic lineage [Recently, the role of mechanical signals in determining and realizing various MMSCdifferentiation programs has been a highly discussed topic . It was Osterix . Other sOsterix and inseOsterix .Interesogravity . It was lineage . Similar lineage .However lineage .MAPK during the process of MMSC osteogenic differentiation in a rotationalbioreactor [\u041c\u0410\u0420\u041a during osteogenic ostoeblast differentiation in a3D\u2013clinostat [Microgravity can modify the differentiation potential of precursor cells through changes inthe activity of the major kinase signal transduction cascades . It was oreactor , 38 or dlinostat have alsThe reciprocal suppression of the two differentiation pathways of MMSC may be attributed tothe existence of other regulatory mechanisms, including those of autocrine and paracrinenature. For instance, the products of one of the differentiation pathways may inhibit theproduction of compunds which are needed for the formation of the other phenotype. Studies haveshown that the lipoprotein lipase produced by adipocytes could bind sortilin, the expression ofwhich was induced during osteogenic differentiation of MMSC, since this receptor protein wasneeded for the normal mineralization of the bone matrix. Moreover, sortilin itself was able tomediate the endocytosis of lipoprotein lipase . Ithas The functional role of most cytokines in the regulation of the MMSC lifecycle and in theadaptation of these and other osteogenic cells to microgravity has not been studied very deeplyand requires further investigations. During recent years, researchers have paid much attentionto the role of IL\u20138. It is known that the expression of the neutrophil\u2013activatingfactor is regulated by IL\u20131 \u03b2 and TNF\u2013a, and also by glucocorticoid hormones.Notably, IL\u20138 can regulate the expression of cell adhesion molecules, and also theexcretion of several enzymes which can degrade the extracellular matrix . These p RhoA caused differentiation into adipocytes, while overexpression of the wild\u2013typegene led to osteogenesis. The authors found that normal actin\u2013myosin tension was requiredfor the correct activation of Rho\u2013kinases by RhoA and suggested that the cytoskeleton andthe regulatory proteins coupled to it could act as an integral regulatory system thatcontrolled cell differentiation decisions, which were mainly defined through mechanical signals[ RhoA , prevented the describedcytoskeleton alterations and neutralized the development of adipogenic features in the cells[MAPKwith the integrin\u2013mediated signaling pathway and also with the activity of severalcytoskeletal effector proteins was demonstrated by switching\u2013off of one of the actincytoskeleton remodeling proteins (Rho), which caused the inactivation of the MAP\u2013kinasecascade [Recently, there are more and more observations giving strength to the idea that cytoskeletalstructures and cell surface receptors connected to them play an imporatant role in theregulation of the differentiation potential of stem cells, which is affected by signals from an\u201cexternal mechanical field\u201d . Also,c signals. Intereshe cells. Direct cascade .Studying all the complex factors that control the commitment of MMSC cell differentiation canhelp elucidate the mechanisms which are required for maintaining the delicate equilibriumbetween the two stem cell differentiation pathways. Deregulation of this equilibrium duringhypokinesia or microgravity can lead to severe medical conditions, such as osteopenia orosteoporosis. In conclusion, it is worth repeating that multipotent mesenchymal stromal cellsof the human bone marrow are the population of cells with low\u2013level commitment which aresensitive to gravitational changes. Despite the growing number of reports on the effect of realor microgravity on the morpho\u2013functional state of various types of cultured osteogeniccells, the precise molecular and intracellular mechanisms of the observed effects are still notfully understood. However, the overall phenomenology of responses from osteogenic cells ofvarious levels of commitment indicates that common mechanisms for sensing and responding toalterations in the gravitation field do exist. Further comprehensive studies in this field willfacilitate fundamental understanding of the mechanisms of gravitational and mechanicalsensitivity of adult precursor cells and their possible involvement in the local cellreactions, which take place in the bone tissue in microgravity.1Grigoriev A.I.Egorov A.D. Human in space flightSpace biology and medicineNaukaMoscow199435495492Oganov V.S. SlovoMoscow20032602603Akiyama H.Kanai S.Hirano M. Mol.Cell Biochem.1999202163714Carmeliet G.Nys G.Bouillon R. J. Bone Miner Res.199712578679491443455Hughes-Fulford M. Cell biology and biotechnology in space Ed by A Cogoli.Advances in space biology and medicine20028129157129516956Hughes-Fulford M.Rodenacker K.J\u00fctting U. J. Cell Biochem.2006992435449166192677Kumei Y.Morita S.Katano H. Ann. 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Res.20052010185818661616074493SordellaR.JiangW.ChenG.C.Cell200311321471581270586494McBeathR.PironeD.M.NelsonC.M.Dev. Cell.2004644834951506878995RenshawM.W.ToksozD.SchwartzM.A.J. Biol. Chem.19962713621691216948702960"} +{"text": "Francisella tularensis subsp. tularensis are associated with unique biotic and abiotic factors that maintain disease foci.Subpopulations A.I and A.II. of Francisella tularensis, is a formidable biologic agent that occurs naturally throughout North America. We examined genetic and spatial diversity patterns among 161 US F. tularensis isolates by using a 24-marker multiple-locus variable-number tandem repeat analysis (MLVA) system. MLVA identified 126 unique genotypes. Phylogenetic analyses showed patterns similar to recently reported global-scale analyses. We observed clustering by subspecies, low genetic diversity within F. tularensis subsp. holarctica, and division of F. tularensis subsp. tularensis into 2 distinct subpopulations: A.I. and A.II. The 2 F. tularensis subsp. tularensis subpopulations also represent geographically distinct groups; A.I. occurs primarily in the central United States, and A.II. occurs primarily in the western United States. These spatial distributions are correlated with geographic ranges of particular vectors, hosts of tularemia, and abiotic factors. These correlates provide testable hypotheses regarding ecologic factors associated with maintaining tularemia foci.The causative agent of tularemia, Francisella tularensis , which is found only in North America, and the moderately virulent F. tularensis subsp. holarctica (type B), which is endemic throughout the Northern Hemisphere and biting flies (Tabanidae) (Dermacentor variabilis), the Rocky Mountain wood tick (D. andersoni), and the Lone Star tick (Amblyomma americanum) was the first tularemia vector to be identified and is often associated with human disease in the western United States and Lepus spp. (hares), are important hosts and biotic and abiotic variables.In this study, we examined genetic-spatial patterns among North American F. tularensis isolates, 158 from the United States and 3 from Canada. Subspecies analyzed included 83 F. tularensis subsp. tularensis, 72 F. tularensis subsp. holarctica, and 6 F. tularensis subsp. novicida. The originating laboratories for a subset of these isolates (n = 80) is reported elsewhere was used to calculate mean elevation in each county of occurrence.A neighbor-joining dendrogram was generated by using PAUP . Distribution maps were generated with ArcView 3.3 ; host and vector distributions were based on previously published data and 1 isolate from California, the other 4 F. tularensis subsp. novicida isolates were collected in southeastern states . No significant correlation was found between genetic and geographic distances within F. tularensis subsp. tularensis subpopulation A.I. or F. tularensis subsp. holarctica .Only within F. tularensis subsp. tularensis A.I. isolates from California (n = 5) are genetically distinct from A.I. isolates found in the other 47 contiguous states (n = 23).Based on ANOSIM, A.I. and A.II. isolates form 2 distinct groups in geographic space . We found no evidence that A. americanum and D. variabilis; both D. variabilis and the A.I. isolates occur primarily in the central and eastern United States but also in California than the mean elevation in counties where A.II. subpopulation genotypes were isolated . The geographic distribution of A.I. isolates is closely associated with the distribution of the vectors lifornia . The maidiscalis . Finallyectively .F. tularensis in the United States and contributes new insights into this human health threat and potential biologic weapon. Our analyses categorized North American F. tularensis isolates into 4 previously recognized groups (13) and provided good genetic resolution within those groups (F. tularensis. We focus here on a more detailed discussion of F. tularensis population structure on a continentwide scale and the ecologic correlates and associations of specific groups.This study provides an ecogenetic analysis of e groups \u20135. TheseF. tularensis subsp. holarctica (F. tularensis subsp. holarctica in the United States, is consistent with rapid transmission of a recently emerged pathogen across great distances.We observed relatively little genetic diversity within larctica despite larctica . The genF. tularensis subsp. holarctica, the A.I. and A.II. subpopulations within F. tularensis subsp. tularensis are genetically distinct and geographically differentiated. The spatial distributions of these 2 subpopulations are associated with large differences in elevation, with A.I. occurring at lower elevations than A.II. Elevation alone is unlikely to influence the distribution of different groups within F. tularensis subsp. tularensis. We examined elevation because it is a single measurement that is highly correlated with other, more biologically relevant factors that may influence host and vector distributions, such as temperature, rainfall, and distribution of major vegetation types (S. floridanus may be an important host for the A.I. subpopulation and S. nuttallii for the A.II. subpopulation (Unlike on types . The A.Ion types . Our respulation .F. tularensis subsp. tularensis are associated with specific vector species, and movement of these vectors may have dispersed the pathogen across the United States. The distribution of the A.I. subpopulation is spatially correlated with A. americanum and the American dog tick D. variabilis (F. tularensis\u2013infected D. variabilis may explain the lack of genetic-spatial correlation within this group, as well as the occurrence in California of both D. variabilis and the A.I. subpopulation of F. tularensis subsp. tularensis. Tularemia-infected D. variabilis could have been introduced into California through dogs during human westward migration in the 19th or 20th centuries. This hypothesis is consistent with the urban distribution of D. variabilis in California (F. tularensis subsp. tularensis A.II. subpopulation is in the western United States and that this focus is associated with the vectors D. andersoni and C. discalis.The A.I. and A.II. subpopulations within riabilis . The traF. tularensis subsp. tularensis may be ancient (F. tularensis subspecies (,The evolutionary linkage of the A.I. and A.II. subpopulations within ancient . Large Mbspecies . The curF. tularensis subsp. tularensis A.I. may have been relatively isolated until European colonists dispersed this pathogen throughout the continent. The rapid and long-range dispersal of infected animals or vectors would be similar to an evolutionary radiation with little correlation to spatial parameters.The lower Midwest tularemia focus , contine,F. tularensis (Such rapid dispersal also may be a function of the recent introduction of lagomorph species into these areas. In the first half of the 20th century, hundreds of thousands of rabbits and hares were shipped from central states to eastern states (F. tularensis subsp. tularensis. Some of the main human incidence hotspots in the United States, Arkansas, Kansas, Massachusetts, Missouri, Oklahoma, and South Dakota (F. tularensis subsp. tularensis A.I. subpopulation or favorable ecologic conditions that promote disease maintenance and transmission in this region.The overall incidence of human tularemia infections in the United States appears to arise from areas where we showed the prevalence of the A.I. subpopulation of h Dakota and 6. TF. tularensis subsp. tularensis and indicate that these groups are geographically distinct and associated with unique biotic and abiotic factors. These findings are important because F. tularensis subsp. tularensis is most often associated with human tularemia in the United States. The ecologic correlates identified here provide a framework for developing testable hypotheses regarding niche separation between the A.I. and A.II. subpopulations and should inform future studies addressing the transmission dynamics and persistence of F. tularensis in North America.Our results confirm the presence of 2 distinct subpopulations within"} +{"text": "There are errors in the Funding section. The correct Funding information is as follows:http://www.onr.navy.mil/en/Science-Technology/Departments/Code-32/All-Programs/Atmosphere-Research-322/Marine-Mammals-Biology.aspx), United States Navy Living Marine Resources, B. Gisiner and F. Stone (http://www.lmr.navy.mil), United States Pacific Fleet, C. Johnson , Pacific Life Foundation, B. Haskell (http://www.pacificlife.com/PL/FoundationCommunity/Overview/Corp_PLF_Home.htm), Ocean Foundation, M. Spaulding (http://www.oceanfdn.org), Naval Postgraduate School, C. Collins and J. Joseph (http://www.nps.edu), National Oceanographic Partnership Program (http://www.nopp.org), the Bureau of Ocean Energy Management, J. Lewandowski and J. Price (http://www.boem.gov), Pacific Islands Fisheries Science Center (PIFSC), National Oceanic and Atmospheric Administration (http://www.pifsc.noaa.gov/cetacean). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Funding provided by United States Office of Naval Research, M. Weise ("} +{"text": "In Vietnam, O. tsutsugamushi was among the most common causes of fever in soldiers.Etiologic agent of scrub typhus, transmitted by the bite of thrombiculid mite larvae. From the Latin Sources: Dorland's illustrated medical dictionary. 30th ed. Philadelphia: Saunders; 2003; Merriam-Webster's collegiate dictionary. 11th ed. Springfield (MA): Merriam-Webster Incorporated; 2003; and Raoult D. Scrub typhus. In: Mandel GL, Bennett JE, Dolin R, editors. Principles & Practice of Infectious Diseases. 6th ed. Churchill Livingstone; 2004. p. 2309-10."} +{"text": "AbstractAll 8237 species-group taxa of Coleoptera known to occur in Canada and Alaska are recorded by province/territory or state, along with their author(s) and year of publication, in a classification framework. Only presence of taxa in each Canadian province or territory and Alaska is noted. Labrador is considered a distinct geographical entity. Adventive and Holarctic species-group taxa are indicated. References to pertinent identification keys are given under the corresponding supraspecific taxa in the data archive. PageBreakChecklist of beetles of Canada and Alaska (Histeridae (Curculionidae subfamily Entiminae (Checklist of beetles of Canada and Alaska will help those interested in beetles of the Canadian fauna.More than twenty years have passed since the publication of the d Alaska . During ionidae) , one on steridae and one ntiminae . FinallyChecklist, this publication is intended to provide the correct names of the beetles that occur in Canada and Alaska, give a brief survey of the distribution of the species in the area covered, and lead the users to useful publications for the identification of the taxa.As for the first edition of the Checklist, or the taxa were described after the publication of the first edition of the Checklist and reported from Canada and/or neighboring states, or the names have been used in recent important works dealing with the Nearctic fauna.The classification of family-group taxa used in this checklist follows The authors of all scientific names are listed along with the date of publication of the taxa. To avoid confusion, initials are included for several authors, such as H.P. Brown, W.J. Brown, H. Clark, W.E. Clark, G. Dellacasa, M. Dellacasa, D.C. Miller, K.B. Miller, W.V. Miller, P.W.J. M\u00fcller, O.F. M\u00fcller, C.R. Sahlberg, R.F. Sahlberg, J.R. Sahlberg, C. Schaeffer, J.C. Schaeffer, E.H. Smith, J.B. Smith, R.F. Smith, S.G. Smith, C.G. Thomson, J. Thomson, A. Zimmermann, C.C.A. Zimmermann as well as W. Horn, and J.E. LeConte. LeConte and Horn stand for J.L. LeConte and G. Horn respectively.PageBreakAn asterisk [*] placed after a species-group name indicates that the taxon is Holarctic, a dagger [\u2020] that it is adventive in North America, and a double dagger [\u2021] that its status is uncertain and the taxon could be Holarctic or adventive on this continent. Species that have been intercepted at ports of entry but are not established in Canada or Alaska are not included in the list.American Beetles . Labrador is considered a distinct geographic entity. The distributional records are based mostly on published records and on specimens in the Canadian National Collection of Insects, Arachnids and Nematodes, in Ottawa although other Canadian and Alaskan collections were surveyed for some groups. Only records considered to be reliable are listed. The absence of a geographic entry after a species-group name indicates that the taxon was recorded from Canada but no province was specified. AlbertaAB New BrunswickNB OntarioON AlaskaAK NewfoundlandNF Prince Edward IslandPE British ColumbiaBC Nova ScotiaNS QuebecQC LabradorLB Northwest TerritoriesNT SaskatchewanSK Manitoba MB NunavutNU Yukon TerritoryYTColeoptera known to occur in Canada and Alaska are included. For a summary of the number of species recorded in each beetle family see All extant described species in the order This checklist includes records from all provinces and territories of Canada as well as the American state of Alaska.PageBreakPageBreakPageBreakPageBreakPageBreakPageBreak1758\u20132013.Object name: Darwin Core Archive Checklist of the beetles (Coleoptera) of Canada and Alaska. Second editionCharacter encoding: UTF-8Format name: Darwin Core Archive formatFormat version: 1.0Distribution: http://dx.doi.org/10.5886/998dbs2aPublication date of the data: 2013-12-06Language: EnglishLicence of use: Open Government License \u2013 Canada, version 2.0 (http://data.gc.ca/eng/open-government-licence-canada#)Metadata language: EnglishDate of metadata creation: 2013-09-06Hierarchy level: DatasetA book which includes a formatted version of the checklist, as well as an index to supraspecific taxa, is also available from Pensoft Publishers."} +{"text": "AbstractTermitinae species Genuotermes spinifer Emerson are redescribed. The gut anatomy of the worker is described in detail for the first time, and morphological variations in the soldier are noted and illustrated. The known geographical distribution of Genuotermes spinifer is greatly expanded.The imago and soldier castes of the Neotropical Termitinae is represented in the Neotropical region by 18 genera and 96 species . All examinated material are from Brazil and listed under the species redescription, arranged by state , and the corresponding lot number from the MZUSP (in parentheses). An asterisk after the lot number indicates the samples that contain imagoes. The GPS coordinates are indicated in decimal degrees, and only in the cases that have been registered by the own collectors. The records of samples deposited in the Museu Paraense Em\u00edlio Goeldi (MPEG), the Instituto Nacional de Pesquisas da Amaz\u00f4nia (INPA) and the Universidade de Bras\u00edlia (UnB) were also included to compose a comprehensive species distribution map. The line drawings were made with a camera lucida, and the photographs were taken with a digital camera coupled to a stereomicroscope at different focal points and merged with software. The enteric valve and crop of a worker were mounted on a slide with glycerin and photographed under an optical microscope.The material examined is deposited in the cross length of mandible, CLM (39); width of head capsule, WH (18); length of head capsule, LH (9); maximum width of pronotum, MWP (68); length of left hind tibia, LT (85). The \u201cdistance from the first marginal teeth to the apex\u201d (DMA) is also included, as explained in The terminology adopted for the worker digestive tube follows Emersonhttp://species-id.net/wiki/GenuotermesGenuotermes spinifer Emerson, by monotypy PageBreakImago. Eyes semispherical, oval in profile, close to but not touching lower margin of head and ocellus elongated, of uniform width, covering half length of mesenteric arch and facing anterodorsal region of body and the interval between the M3 and molar plate is narrow. Other unusual characteristics of this species are the thorax and abdomen covered only with decumbent bristles, without any erect setae or bristle.Soldiers. Genuotermes soldiers have a combination of characters that make it easily distinguishable from other Neotropical Termitinae genera. Genuotermes and OrthognathotermesIsoptera; however, there are some clear differences between the two genera. Genuotermes has a projection on the anterior dorsal region of the head, which is absent in Orthognathotermes. The frontal gland aperture is recognizable at the apex of projection, whereas in Orthognathotermes the aperture is inconspicuous. In the remaining Termitinae genera with similar head structures the gland opening is situated on the base of their respective projections. In the Genuotermes soldier the molar plate and prominence are visible at the base of the mandibles insertion is situated on the right side of the body; and the armature is composed of cushions with projections to the P3 lumen , from Brazil, Mato Grosso do Sul state, Serra do Urucum , 14.viii.1926, K.P. Schmidt coll. (not examined).vide supra). Measurements. See As for the genus (vide supra). Measurements (mm): DMA: 1.05\u20131.40; CLM: 1.65\u20131.95; WH: 1.05\u20131.25; LH: 1.50\u20131.75; MWP: 0.68\u20130.93; LT: 0.85\u20131.00.As for the genus (vide supra).As for the genus . They probably feed on humus in subterranean galleries. The morphology of the worker mandibles (humivorous type) and the finding of sand particles in the gut concord with this hypothesis.Information about the life habits of Genuotermes spinifer presented here represent a significant extension of the previously known distribution. The species\u2019 occurrence now includes different vegetation zones, the Brazilian Cerrado and the Amazon Forest.The records of PageBreakAmazonas: Itacoatiara, 04.xi.1977, A. Bandeira (7479); 23.v.1977 (8353). Goi\u00e1s: Cana Brava (Faz. Ita\u00fana), 07.v.1975, K. Kitayama (7310). Mato Grosso: Cuiab\u00e1 (14 Km NW), 15.ii.1976, R.L. Araujo (6526); Cuiab\u00e1 , 06-10.viii.2009, S.P. Rosa (12643); Chapada dos Guimar\u00e3es, 10.ii.1976, R.L. Araujo ; Cotrigua\u00e7u , 29.xi.2011, R.C. Paula (16352); Coxip\u00f3, 14.ii.1976, R.L. Araujo (6703); 18.ii.1976 (7217); 17.ii.1976 (6857); Serra do Roncador, ix\u2013x.1968, A.G.A. Mathews . Par\u00e1: Belterra, 31.i.1949, C.R. Gonl\u00e7alvez (4306); Fordl\u00e2ndia, ii.1957, A.M. Almeida (8383). Piau\u00ed: Floriano, 5\u201312.xi.1991, E.M. Cancello and M.T. Ponte (10188); Sete Cidades, 14.xii.1976, R.L. Araujo (7194). Rond\u00f4nia: Porto Velho , 26.ii\u201313.iii.2010, T. Carrijo and R. Santos (13009); Porto Velho , 08.iv.2011, R. Santos and C. Mandai (16355); 09.ix.2011, R. Santos and J. Cabral (16253); 06.iii.2012, T. Carrijo and J. Cabral (16356); Porto Velho , 18.ix.2010, T. Carrijo and R. Santos (16354*).BRAZIL. PageBreak"} +{"text": "AbstractCamptochaeta prolixa sp. n. is described from caves in Nevada, and three other congeneric species are recorded from caves in Nevada and Arkansas, United States. The new species shows some indication to a subterranean mode of life, including long antenna and legs, and in some specimens, reduction of the eye bridge. Camptochaeta Hippa & Vilkamaa, 1994 includes three species which have been found in caves: Camptochaeta ofenkaulis and Camptochaeta scanica Hippa & Vilkamaa, 1994 and Camptochaeta subcamptochaeta see . Of thesSciaridae, only specimens of \u2018Corynoptera sp.' have been recorded from a cave in Arkansas . Paratypes, dissected and mounted as the holotype: 1 male, same data but dry calcite floor, G.M. Baker, S.J. Taylor & J.K. Krejca (in USNM); 1 male, Nevada, White Pine County, Lehman Cave, 25.vi.2006, G.M. Baker, M.A. Horner & B. O'Doan (in INHS); 1 male, same locality but dry calcite wall, hand collection, 26.v.2006, S.J. Taylor, J.K. Krejca, M.E. Slay & G.M. Baker (in MZH); 2PageBreak males, Lehman Cave Annex, under rocks, hand collection, 25.v.2006, S.J. Taylor, J.K. Krejca, M.E. Slay B. Roberts, & M. Horner (in MZH); 1 male, Nevada, White Pine County, Cave 24, hand collection, 17.vii.2007, G.M. Baker & S.J. Taylor (in MZH). Other material. 1 female, Nevada, White Pine County, Lehman Cave, PageBreakunder rocks, hand collection, 25.v.2006, S.J. Taylor, J.K. Krejca, M.E. Slay, B. Roberts, & M. Horner (in MZH).Head. Brown, maxillary palpus very pale brown, antenna concolorous with face at base but paler towards apex. Eye bridge 1\u20132 facets wide, medially lacking ommatidia, sometimes narrowed into stripe. Face with 5\u20138 scattered setae. Clypeus with 1 seta. Maxillary palpus with 3 palpomeres; palpomere 3 longer than palpomere 1, palpomere 2 shortest; palpomere 1 with one (rarely 2) long sharp seta, with a dorsal pit with long sensilla; palpomere 2 with 3 (rarely 4) long sharp setae, 7\u20139 shorter truncate setae, palpomere 3 with 8\u201312 short truncate setae. Antenna long, antennal flagellomere 4, Thorax. Concolorous brown, setae pale. Anterior pronotum with 3\u20136 setae. Episternum 1 with 5\u20138 setae. Wings. Length 2.4\u20132.8 mm. Width/length 0.35\u20130.40. R1/R 0.85\u20131.05. c/w 0.65\u20130.70. r-m with 2\u20135 setae, bM non-setose. Halter pale brown. Legs. Yellowish, long. Metatarsus long, probasitarsomere as long as profemur; the modified vestiture of protibia pale, in patch in shallow depression. Protibial spur slightly longer than tibial width. Abdomen. Pale brown. Setae pale and long. Hypopygium, Male. Female. Slightly larger than male, wing length 3.0 mm, without diagnostic characters. Camptochaeta prolixa isvery similar to Camptochaeta subcamptochaeta found in central European caves, and the very similar Camptochaeta pentacantha found in the Altay, Russia. Camptochaeta prolixa differs from both by having a more slender gonostylus and by having the antennal flagellomeres longer, in most specimens more than five times as long as wide, with longer setosity; and by having a narrower eye bridge. Camptochaeta prolixa and resembles the European cave-dwelling Camptochaeta ofenkaulis by having long antenna and legs, but the gonostylus is remarkably different. Some specimens of C. prolixa show a tendency to a reduced eye bridge, which in addition to the long legs and antenna may be an accommodation to the subterranean mode of life.Camptochaeta prolixa were collected in the dark zones of caves, and one in the twilight zone. Based on microhabitat-specific data for ten specimens: air temperature ranged from 6.6 to 13.0 C, average 10.9 C; relative humidity ranged from 82.6 to 92.4 %, average 87.7 %; light ranged from 0 to <1 lux, average 0.0 lux; and elevation ranged from 2089 to 2013 m, average 2228 m. All Camptochaeta prolixa specimens were collected in May (9 specimens) and July (2 specimens), even though sampling was carried out monthly in Lehman Caves. Most specimens were associated with bedrock or calcite walls or ceilings.Ten of the 11 specimens of prolixa, streched out, referring to the very long extremities of the fly.PageBreak The name is Latin (adjective), Camptochaeta mutua 9 males, USA, Arkansas, Stone County, Blanchard Springs Caverns, 27.iv.2002, M. Slay, G. Graening & K. Tinkle (in MZH).Camptochaeta mutua was described from Ithaca, New York ; 1 male, White Pine County, Root Cave, calcite wall, hand collection, 25.v.2006, S.J. Taylor, G.M. Baker & B. Roberts (in INHS).Camptochaeta pellax were collected from the dark zone of caves, with the following microhabitat-specific data: air temperature ranged from 10.9 to 13.0 C, average 11.95 C; relative humidity ranged from 84.4 to 88.6 %, average 86.5 %; light 0 lux; elevation ranged from 2089 to 2235 m, average 2162 m. Camptochaeta pellax is earlier known only from the type material from Colorado .Camptochaeta spicigera was collected in the entrance zone of a mine on wet rocks above water on the mine floor, with the following microhabitat-specific data: air temperature 9.7 C; relative humidity 52.5%; light 1755 lux; elevation 2621 m. Camptochaeta spicigera is earlier known only from the type material from Colorado (The Nevada specimen of Colorado .The distributions of temperature and humidity data for the new species are consistent with the morphological evidence that this species is a troglobite. Only one specimen was found in the twilight zone, and with the exception of that specimen, the species was always associated with elevated relative humidity and stable temperatures consistent with deep-cave habitats.Camptochaeta brings the number of recently described cave organisms from Great Basin National Park to five. The sampled caves span a range of 1724 to 3413 meters in elevation, crossing a variety of vegetation zones from to above timberline. Within the caves, there are a variety of microhabitats with varying levels of nutrient input and habitat stability. In addition, the Park is located in a relatively sparsely populated area, with few entomologists. A combination of these factors may account for the relatively high number of new species recently described from this area.Our description of a new"} +{"text": "G.J.D. is a member of the scientific advisory board of Alectos Therapeutics. D.J.V. is a founder, shareholder, consultant, and member of the scientific advisory board of Alectos Therapeutics.Chemistry & Biology apologizes for this omission."} +{"text": "Current Genomics. Their efforts have contributed greatly to the high quality and continuous growth of the journal. Given below is the list of reviewers who reviewed articles for the Journal during 2012: A. CarvalhoAl. GjumrakchB. TaylorC. PagniniE. CornerE. ReszkaJ. ParkJ. BadanoJ. DuranJ. ZhuaJun QinA. ListonM. SzaumkesselM. HaqueM. HarperM. Kauffman.M. XiongP. AdlerP. HerrR. ChahwanR. KohliS. JohnsenU. StelzlBentham Science Publishers would like to thank and appreciate the co-operation from all reviewers for their constructive comments and feedback on the manuscripts submitted to"} +{"text": "Triticum aestivum L.) chromosome 3B, it has been estimated that 90% of the cross over events occur in distal sub-telomeric regions representing 40% of the chromosome. Radiation hybrid (RH) mapping which does not rely on recombination is a strategy to map genomes and has been widely employed in animal species and more recently in some plants. RH maps have been proposed to provide i) higher and ii) more uniform resolution than genetic maps, and iii) to be independent of the distribution patterns observed for meiotic recombination. An in vivo RH panel was generated for mapping chromosome 3B of wheat in an attempt to provide a complete scaffold for this ~1 Gb segment of the genome and compare the resolution to previous genetic maps.The uneven distribution of recombination across the length of chromosomes results in inaccurate estimates of genetic to physical distances. In wheat (i) the overall resolution of the RH map was 10.5 fold higher and ii) six fold more uniform. A significant interaction (r\u2009=\u20090.879 at p\u2009=\u20090.01) was observed between the DNA repair mechanism and the distribution of crossing-over events. This observation could be explained by accepting the possibility that the DNA repair mechanism in somatic cells is affected by the chromatin state in a way similar to the effect that chromatin state has on recombination frequencies in gametic cells.A high density RH map with 541 marker loci anchored to chromosome 3B spanning a total distance of 1871.9 cR was generated. Detailed comparisons with a genetic map of similar quality confirmed that in vivo the hypothesis of non-casual interaction between recombination hot-spots and DNA repair. Further, two major hypotheses are presented on how chromatin compactness could affect the DNA repair mechanism. Since the initial RH application 37\u2009years ago, we were able to show for the first time that the iii) third hypothesis of RH mapping might not be entirely correct.The RH data presented here support for the first time Triticum aestivum L.), recombination events are not evenly distributed along the length of the chromosomes . All PCR protocols have been described previously [Genotyping was conducted with three classes of markers: cfp are PCR-based ISBP ,57; barcrra, AU) . To guareviously ,39,56,57eviously . The deleviously was modiAll correlation analyses were performed using the SAS 9.3 environment and the correlation significance was determined on the basis of the Pearson product\u2013moment correlation coefficient for a two-tail test with N-2 degrees of freedom, where N is the number of deletion bins considered .RH: Radiation hybrid; DSB: Double strand break; HR: Homology-directed repair; NHEJ: Non-homologous end-joining; BAC: Bacterial artificial chromosome; cR: centi Rays; Gy: Gray; ISBP: Insertion site based polymorphism; SSR: Simple sequence repeat; DArT: Diversity Array Technology; BR: Break/repair; CO: Crossing over; LDN: \u2018Langdon\u2019; LDN 3D(3B): \u2018Langdon\u2019 with chromosome 3B substituted by chromosome 3D; DEASY: Duplexing EASY.The authors declare that they have no competing interests.A.Kumar, F.M.B., E.P., M.M. de J., Y.Q.G., C.F., and S.F.K designed research; A.Kumar, F.M.B., M.M. de J. S.K., A.G., V.T. and M.D. performed the research; E.P., E.H., A.Kilian, and C.F. provided access to advanced analytical tools and unpublished data; O.Al-A. and A.M.D. developed iterative framework mapping script; H.S.B., H.S.D., P.K.G., and G.S.R. provided support for student interns A.Kumar, S.K., A.G., and V.T.; F.M.B., A. Kumar, E.P., M.M. de J., W.P.P and E.H. analyzed the data; F.M.B, A.Kumar, E.P.,W.P.P., S.F.K. wrote the paper, M.J.I. and S.F.K. managed the project. All authors read and approved the final manuscript.Supplementary text, tables and figures. The file contains supplementary text, Table S1, Figure S1, S2 and S3. Suppl. Text describes the rational of radiation hybrid mapping, the algorithm developed to exploit the specific characteristics of this type of mapping, and its proof of concept. Table S1 presents the statistical details of the iterative frame work mapping approach applied to the radiation hybrid map of chromosome 3B. Figure S1 shows the superior marker order conservation between 3B-radiation hybrid (3B-RH) map and the 3B genetic map when employing iterative frame work mapping algorithm, instead of a non-iterative approach. Figure S2 shows how the error in marker order conservation between the 3B-RH map and the 3B genetic map is lower than the error that exists between published genetic maps. Figure S3 shows that marker loci have non significantly different deletion frequencies throughout the 3B chromosome [romosome ,41,59.Click here for file"} +{"text": "There is an update to the fifth author's affiliation. Stephen S.-T. Yau's affiliation is: \"Department of mathematical sciences, Tsinghua University, Beijing, P.R. China\""} +{"text": "After the publication of this manuscript we observed mistakes in Figures 3A, 4A, and 6A. The representative images related to pAkt , mTOR total , and MuRF-1 total have been revised. Please note the original raw blots are now provided with the revised Figures as part of this Correction.In Figure 3A, pAkt panel, the C and CS bands had been duplicated.In Figure 4A, the bands were re-arranged compared to the original blot.In Figure 6A, the band for group D was incorrect.The remaining Figures, results and conclusions are the same as originally reported in the article. The authors apologize for these errors and refer readers to the corrected Figures 3A, 4A, and 6A provided in this Correction.http://www.plosone.org/corrections/pone.0050390.g003a.cn.tifFigure 3A: http://www.plosone.org/corrections/pone.0050390.g003a_blot.cn.tifFigure 3A blot: http://www.plosone.org/corrections/pone.0050390.g004a.cn.tifFigure 4A: http://www.plosone.org/corrections/pone.0050390.g004a_blot.cn.tifFigure 4A blot: http://www.plosone.org/corrections/pone.0050390.g006a.cn.tifFigure 6A: http://www.plosone.org/corrections/pone.0050390.g006a_blot.cn.tifFigure 6A blot:"} +{"text": "Importantly, as the loop continues to execute, more rules can be extracted from the evolutionary algorithm itself by simply identifying the changes across the generations that produced improvement, and mapping that information onto the fuzzy logic domain.As of late, automated methods for generation and tuning of neuronal models have been gaining popularity (e.g. ). Severa.g. [e.g.) or parte.g.[e.g.), have be.g.[e.g.,5). Multe.g.[e.g.,7). The e.g.[e.g.. Fuzzy I"} +{"text": "Resina ferulae were analyzed for essential oil composition, Ferula sinkiangensis K. M. Shen, Ferula fukangensis K. M. Shen, and Ferula ovina, investigated differences among different genera of medicinal R. ferulae.Three cultivars seeds of The essential oils were extracted by the method of hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), using normalization method to calculate relative amount.F. sinkiangensis K. M. Shen, comprised 99.001% of total essential oil; 21 compounds were identified in F. fukangensis K. M. Shen, comprised 100% of total essential oil; 25 compounds were identified in F. ovina, comprised 99.459% of total essential oil. n-Propyl sec-butyl disulfide is the main component in three cultivars seeds of R. ferulae, accounting for 55.875%, 49.797%, 53.781%, respectively.Twenty-six compounds were identified in R. ferulae from Xinjiang.Little diversity among three cultivars seeds of Ferula sinkiangensis K. M. Shen is a genus of the Umbelliferae that used in TCM for a long time by China, and grow in Xinjiang of China. The resin from F. sinkiangensis K. M. Shen and Ferula fukangensis K. M. Shen are recorded in \u201cPharmacopoeia of People\u2019s Republic of China\u201d in F ovina, which pharmacological effects need further research.At the same time, three cultivars seeds of R. ferulae needs further research.The category of chemical compounds in the essential oil of the three cultivars seeds are showed in R. ferulae. Also is reliable evidence of clinical utilization of the three cultivars seeds from R. ferulae. At the same time, provide further research foundation and methods of exploring which composition play an important role in its effects among the three cultivars seeds from R. ferulae, according to the analysis of composition."} +{"text": "There were two errors in the byline. The equal contributions designation was missing. Authors Sellamuthu S. Gounder and Sankaranarayanan Kannan contributed equally to this work. Also, the fifth author's name was incorrect. Kevin J. Whitehead is the correct name. The correct citation is:Gounder SS, Kannan S, Devadoss D, Miller CJ, Whitehead KJ, et al. (2012) Impaired Transcriptional Activity of Nrf2 in Age-Related Myocardial Oxidative Stress Is Reversible by Moderate Exercise Training. PLoS ONE 7(9): e45697. doi:10.1371/journal.pone.0045697"} +{"text": "There is an error in the name of the fourth author. The first name should be \"S.W. Steven\", and the last name should be \"Shaw\". The correct citation is:Lin S-Y, Hsieh C-J, Chen Y-L, Shaw SWS, Lin M-W, et al. (2013) The Impact of Down Syndrome Screening on Taiwanese Down Syndrome Births: A Nationwide Retrospective Study and a Screening Result from a Single Medical Centre. PLoS ONE 8(9): e75428. doi:10.1371/journal.pone.0075428"} +{"text": "In Smallpox Research Activities: U.S. Interagency Collaboration, 2001 by James LeDuc et al., an error occurred in the text on Page 744, left column, under Diagnostic Tests, line 25. The information provided between lines 10 and 25 should be attributed to S. Ibrahim, U.S. Medical Research Institute of Infectious Diseases as unpublished data.http://wwwnc.cdc.gov/eid/article/8/7/02-0032_article.htmThe corrected article appears online at We regret the omission."} +{"text": "Health as the product of a combination of many factors, including biological, psychological, spiritual and social conditions. (Recent improvements in psychological, medical, and physiological researches have led to a new way of thinking about health and illness. This conceptualization, which has been known as the bio- psycho-social model, interprets. Recent improvements in psychological, medical, and physiological researches have led to a new way of thinking about health and illness. This conceptualization, which has been known as the bio- psycho-social model, interprets ditions. . Health ditions. . It is cditions. . Interacditions. . it has ditions. . By traiditions. . While tditions. . Technolditions. . As mediditions. . In the ditions. . At the ditions. . Studiesditions. , these vditions. . This imditions. . I'd sug"} +{"text": "Icosta malagasii (one), Ornithoica podicipis (ten) and Ornithoctona laticornis (six). The two former species were previously only known from single specimens in museum collections; the later species is distributed across much of the Afrotropical region and the records presented herein are the first for Madagascar. All the seven bird species are new hosts for hippoboscids. We present the first description of the male of Icosta malagasii. An illustrated dichotomous determination key of the 14 Malagasy species, based on morphological criteria only, is presented.The Hippoboscidae or \u201clouse-flies\u201d is a family of pupiparous Diptera, which in their adult stage are ectoparasites of mammals and birds. This paper presents a comprehensive review of Malagasy Hippoboscidae. In total, amongst the 213 species of this family known worldwide, 14 have been reported in Madagascar, among which six are considered as endemic to the Malagasy region. In addition, data are presented from a collection of 17 Hippoboscidae obtained from seven species of forest-dwelling birds in the \u201cParc National de Midongy Befotaka\u201d, southeastern Madagascar, in 2003. The flies in this collection belong to three different species: The members of the family Hippoboscidae, known as \u201clouse flies\u201d or \u201ckeds\u201d, are obligate ectoparasites of mammals and birds. Members of this Diptera family consist of winged species, some of which have considerable flight capacity, while other species are flightless and highly apomorphic, having vestigial or no wings. Hippoboscidae belong to Pupipara \u201cpupa-bearers\u201d, in reference to the fact that, unlike virtually all other insects, most of the larval development takes place within the mother\u2019s abdomen and pupation occurs almost immediately after pre-pupae laying . The Hipsensu stricto.Caution must be taken with the name Hippoboscidae. In old taxonomic treatments, it was used to encompass the Hippoboscidae as defined today, as well as the bat-flies (Nycteribiidae and Streblidae). Megatrypanum (Haemoproteus (an apicomplexan parasite of birds). Melophagus ovinus louse flies play a role in the transmission of Bartonella among ruminants . In addition, we propose the first illustrated dichotomous determination key for the genera and species currently known from Madagascar. Recent specimens of hippoboscids have been collected from Malagasy vertebrates and remain unstudied by fly specialists , while the identity of the male remains unknown.Information on Malagasy Hippoboscidae is rather limited and notably dispersed in the scientific literature. We found published records of 13 species recorded at least once on Madagascar. The host species (when known) and/or the context for Madagascar are presented in Allobosca is composed by only one known species, A. crassipes. This species, considered endemic to Madagascar, has rudimentary wings and is known from several species of lemurs .The genus f lemurs . Proparanal Park . Most ofIcosta malagasii is only known by one female. It was collected as a \u201cparasite sur l\u2019aile d\u2019un Coezach/ Sahafanjana/N: 115/R. M./ Inst. Sci. Madagascar\u201d (Coua (subfamily Couinae). In certain Malagasy dialects, the last syllable of the vernacular name is accented and harshly pronounced. In the Parc Botanique et Zoologique de Tsimbazaza, Antananarivo (previously known as \u201cInstitut de Recherche Scientifique de Madagascar\u201d) there is a male specimen of C. caerulea, collected on 12 April 1955 by \u201cR.M.\u201d at Sahafanjana. This information gives credence to the identity of the \u201cCoezach\u201d as a Coua.agascar\u201d . SahafanOrnithoctona idonea is only known by one male and two females with two of these specimens, including the male holotype, being from Madagascar , collected in \u201cAfrica\u201d and designed as a paratype by Ornithoctona laticornis, but subsequently (1969a) retained O. idonea as a dubious species waiting for the rediscovery of the holotype or the availability of new material from Madagascar.dagascar . Theses Pseudolynchia canariensis, the pigeon louse fly, is found in most parts of the tropical and sub-tropical areas of the world and associated with domestic pigeons and doves. Pseudolynchia canariensis is the vector for the Apicomplexa protozoan Haemoproteus columbae, a parasite that can be fatal to young pigeons.Hippobosca variegata, a species distributed in sub- Saharan Africa and Asia, has also been observed in the Comoros Archipelago, specifically on Grande Comore and Mayotte . Following O. idonea \u201cwould be separable from O. laticornis in having antennal appendage relatively more acute at apex, palpus longer, mesosternal processes closer to each other and posterior marginal bristles on laterite two much shorter.\u201dThe determination of these Hippoboscidae flies used Icosta malagasii, Ornithoica podicipis, and Ornithoctona laticornis. The two former species were previously only known from single museum specimens and are here represented in the Midongy Befotaka collection by an additional one and ten individuals, respectively. Further, based on this material, the male of I. malagasii can now be described (see below) and for the first time O. laticornis is documented on Madagascar.In total, 17 Hippoboscidae specimens were collected from 11 individual birds belonging to seven different bird species . They beI. malagasii had been collected from Accipiter francesii; Ornithoica podicipis from Atelornis pittoides, Accipiter francesii, Otus rutilus, Brachypteracias leptosomus, and Streptopelia picturata; and O. laticornis from Atelornis crossleyi, Atelornis pittoides, and Monticola sharpei.New records include collection of O. laticornis because they perfectly match Maa\u2019s description , with the identification of five new host birds for this hippoboscid. Given the high level of endemicity of Malagasy birds at different taxonomic levels, including 51% of the 209 nesting bird species as cription . However species , it is ries e.g.. PerhapsThe male is very similar to the female, as described by \u2022 Key to Genera of HippoboscidaeAllobosca 1- Wing abnormal in size, frons longer than wide, hind femur almost as long as thick and fore tarsus with spatulate setae ........- Wing fully developed and functional .................... 2r-m, im) ............................................................................... 32- Wing with 2 or-m, im, mcu). Ocelli present ...................................................................................... 5- Wing with 3 crossveins )3- Wing with only - Wing with two crossveins ....................................... 4Hippobosca4- Wing with 2 delineated crossveins, wing membrane of all open cells distinctly wrinkled. Pronotum large and forming an observable neck-like segment between head and mesonotum. Ocelli always absent ...... im with a transparent whitish spot ........- Tarsal claws bidentate but seemingly trifid ........Ornithoica6- Wing densely ciliate along apical and anal margins and setulose at apical area. Vertical bristles each arising from nipple-like tubercle . HumeralM1+2, M3+4 and anal vein ending a short distance before wing margin ardeae ardeae - Venter of all femora bare besides few marginal setae ...................................................................................... 21m et 2m, cell 1m fully covered except a basal bare spot very close to M3+4; cell 2m almost entirely bare except at apex where setulae projecting anterally in a sharp process malagasii Maa, 1969- Tarsus 1 not apically asymmetrical. Lateral fence of \u2640 urogenital area composed of 5\u00a0\u00b1\u00a0robust setae which are hardly longer than width of infra anal plate. Setae around \u2642 abdominal spiracles 3-5 almost uniformly fine. Mesosternal process hardly visible. Metabasisternum never produced into posterolateral process .Icosta (Ornithoponus) minor Bigot, 1858Ornithoctona Speiser, 1902\u2022 Key to species of the genus 1- Wing membrane entirely bare, at most with a very narrow setulose line on costal margin near apex; anterior mesosternal process distinctly shorter than interdistance of their apices; posterior ocelli hardly farther from each other than from anterior ocellus. Female abdomen lacking median tergal plates. Wing not less than 7\u00a0mm long.Ornithoctona plicata von Olfers, 1816- Wing membrane setulose ........................................ 23r and 1m sometimes even apex of 2r as well. Anterior mesosternal process narrow, distinctly longer than wide at base. Anterior ocellus situated on or slightly above level of posterior eye-margins. Female abdomen with 3 median tergal plates. Wing not more than 7.5\u00a0mm long - Wings partially setulose. Para-anal laterite bearing 3 to 4 long setae. First sternite rectangular and narrow with many rows of spine-like setae of unequal length on the posterior edge. Ocelli area equilateral triangle shaped. Female abdomen with 3 median tergal plates .Plate 6.Ornithoctona idoneaOrnithoica Rondani, 1878\u2022 Key to species of the genus 2m and extending to apical 1/2 or more of 2r and to apical margin of r-m. Mesoscutum except small areas at its anterolateral corners, as densely setose as prescutum and scutellum. Bare area at base of cell 3r much less than 2\u00a0\u00d7\u00a0as that of 1m.1- Wing size 3.2-3.5\u00a0mm. Wing-setulae covering more than 1/2 of cell Ornithoica (Ornithoica) podicipis von R\u00f6der, 18922m, generally forming very small patch near its antero-apical corner; cell 2r at most setulose at extreme apex. Cell r-m entirely bare, setulose area in cell 2m small confined to antero-apical corner (- Wing size 2.5-2.8\u00a0mm. Wing-setulae covering much less than 1/2 of cell l corner .Ornithoica (Ornithoica) hovana"} +{"text": "Vibrio vulnificus is a virulent, gram-negative, comma-shaped, motile bacterium that belongs to the family Vibrionaceae. In 1976, researchers at the Centers for Disease Control identified it as a Vibrio sp. and possible emerging pathogen. Because of its association with blistering skin infections, the bacterium was named Vibrio vulnificus in 1979. From the Latin PubMed;Hollis DG, Weaver RE, Baker CN, Thornsberry C. Halophilic Vibrio species isolated from blood cultures. J Clin Microbiol. 1976;3:425\u201331. PubMed;Todar K. Todar\u2019s online textbook of bacteriology. Vibrio vulnificus. [cited 2010 Nov 24]. http://textbookofbacteriology.net/v.vulnificus.html; Dorland\u2019s illustrated medical dictionary. 31st ed. Philadelphia: Saunders Elsevier; 2007.Sources: Farmer JJ III. Vibrio (\u201cBeneckea\u201d) vulnificus, the bacterium associated with sepsis, septicaemia and the sea. Lancet. 1979;2:903."} +{"text": "Arthrobacter sp. W1.The word \"Biotransformation\" is misspelled in the article title. The correct title is: Characterization of a Novel Phenol Hydroxylase in Indoles Biotransformation from a Strain Arthrobacter sp. W1. PLoS ONE 7(9): e44313. doi:10.1371/journal.pone.0044313 The correct citation is: Qu Y, Shi S, Zhou H, Ma Q, Li X, et al. (2012) Characterization of a Novel Phenol Hydroxylase in Indoles Biotransformation from a Strain"} +{"text": "There is an error in the names of the second and third authors. The corrected names are Molly F. Franke and Jessica E. Teng, respectively. The citation should read as follows:Aibana O, Franke MF, Teng JE, Hilaire J, Raymond M, et al. (2013) Cholera Vaccination Campaign Contributes to Improved Knowledge Regarding Cholera and Improved Practice Relevant to Waterborne Disease in Rural Haiti. PLoS Negl Trop Dis 7(11): e2576. doi:10.1371/journal.pntd.0002576"} +{"text": "There were multiple omissions of multiple authors' additional contributions to the article in the Author Contributions Statement. The following should be included in the Author Contributions Statement: \"Conceived research: A.D., F.C.Z.Discussed the conceptual and practical implications of the method at all stages: F.C.Z., A.D., Z.L., M.F., L.F.\""} +{"text": "AbstractCarica papaya L. is sister to a Mexican/Guatemalan clade of two genera, Jarilla Rusby with three species and Horovitzia V.M. Badillo with one. These species are herbs or thin-stemmed trees and may be of interest for future genomics-enabled papaya breeding. Here we clarify the correct names of Jarilla heterophylla (Cerv. ex La Llave) Rusby and Jarilla caudata (Brandegee) Standl., which were confused in a recent systematic treatment of Jarilla (Jarilla and Horovitzia, and notes on their habitats and distribution.Using molecular data, we recently showed that Jarilla . We desi Caricaceae Dumort. comprises 34 species and one formally named hybrid in currently six genera. A molecular phylogeny that included all species revealed that Carica papaya L. (the only species in the genus Carica) is sister to a clade of four species endemic to Mexico and Guatemala V. M. Badillo, has implications for plant breeders, who have so far tried in vain to cross papaya with tree species in the genus Vasconcellea A. St.-Hil., known as the highlands papayas. To facilitate communication among researchers from different fields, and since full-genome sequencing of the species of Jarilla and Horovitzia is ongoing , we here provide a conspectus of the four species that are the closest relatives of papaya and clean up a nomenclatural confusion involving two names in the genus Jarilla.The family uatemala . The disWe start with the nomenclatural issues, then provide a key to the four species, and end with brief comments on the range and habitat of each species.Caricaceae that are today placed in Jarilla. He had access to fruiting specimens only and based his description of the flowers on notes made by Vicent Cervantes, a professor of botany in Mexico City and one of the founders of that city\u2019s botanical garden in 1788. La Lave gave his new species the epithet \u201cheterophilla\u201d [sic] to refer to its variably shaped leaves. To mark the distinctness of the new species, he placed it in a separate genus, Mocinna, honoring the Mexican naturalist Jos\u00e9 Mariano Moci\u00f1o. Unfortunately, this overlooked that Lagasca in 1816 had already described an Asteraceae genus by that name. Soon thereafter, George Carica nana, based on an unnumbered Hartweg specimen , probably due to a misreading of 288 for 255.Pablo de specimen collectespecimen bears thCaricaceae species was named in March 1894 by Townshend S. Brandegee, who described Carica caudata from the Cape region of Baja California, Mexico, based on a plant he collected the year before Rusby. We agree with Diaz-Luna and Lomeli-Senci\u00f3n (1992)PageBreak and Jarilla meets the requirement for valid publication and that Ivan M. Jarrilla (the correct Spanish spelling) to replace Mocinna is a superfluous name. At around the same time, Carica caudata Brandegee belonged in Jarilla and was in fact an older name for Jarilla heterophylla var. sesseana Ram\u00edrez (= Jarilla sesseana (Ram\u00edrez) Rusby), and he accordingly changed the name to Jarilla caudata. He also described a third herbaceous species of Caricaceae, Jarilla chocola Standley, based on two collections made in 1935 from Sonora, Mexico leaves, c. 1 cm (rarely longer) male flowers, and 10 cm long fruits that are narrowed at the base with five horn-like appendages, each 3\u20136 cm long PageBreakPageBreakPageBreakStandl.) are in MEXU and NY. Isoepitypes of Mocinna heterophylla Cerv. ex La Llave (= Jarilla heterophylla (Cerv. ex La Llave) Rusby) are in MEXU, NY and K.To fix the usage of the two names more reliably, we below designate epitypes to serve as interpretative specimens for plates II and V of Jarilla/Horovitzia clade can be distinguished from all other Caricaceae and from each other, using a combination of the plastid markers trnL-trnF and psbA-trnH (The four species in the (Lorence & R. Torres) V.M. Badillo, Rev. Fac. Agron. (Maracay) 43: 104. 1993.http://species-id.net/wiki/Horovitzia_cnidoscoloidesCarica cnidoscoloides Lorence & R. Torres, Syst. Bot. 13(1): 107\u2013109, f.1. 1988.R. Torres & P. Teonorio 8168 . Mexico. Oaxaca. Type locality, 25 May 1883, T. Cedillo & Lorence 2347 ; 4 Ago 1985, Lorence et al. 4733 ; 9 Mar 1985, C. Torres & L. Tenorio 8167 (paratype: MEXU); 27 Ago 1986, C. Torres & L. Tenorio 8760 (paratype: MEXU).Mexico. Oaxaca: Ixtlan, Sierra de Ju\u00e1rez, 9 March 1986, Horovitzia cnidoscoloides is a small tree, 0.5\u20134 m tall endemic to Sierra de Juarez in Oaxaca, Mexico. It occurs in cloud forests from 800 to 1600 m above sea level. Unusual features are subcapitate stigma, and stinging hairs covering the entire plant.Standl. Publ. Field Mus. Nat. Hist., Bot. Ser. 17: 200. 1937.http://species-id.net/wiki/Jarilla_chocolaH. S. Gentry 2366 . Mexico. Sonora: San Bernardo, Rio Mayo, 14 August 1935, H. S. Gentry 1624 .Mexico. Sonora: Chihuahua, Guasarema, Rio Mayo, 10 August 1936, PageBreakPageBreakJarilla chocola is an erect herb, with mostly lobate leaves and fruits with 5 longitudinal wings. The species occurs at low altitudes (100\u20131300 m) along the Pacific Coast from Sonora to El Salvador.(Brandegee) Standl., Contr. U.S. Natl. Herb. 23(4): 853. 1924.http://species-id.net/wiki/Jarilla_caudataCarica caudataBrandegee s.n. (holotype: UC[UC108333]). Brandegee, Zoe 4: 401. 1894. Type: Mexico. Baja California Sur: Corral de Piedra, September 1893, Mocinna heterophyllasesseana Ram\u00edrez, Anales Inst. Med.-Nac. Mexico 1: 207. 1894. Type: Plate II of Ram\u00edrez, 1894 . var. Jarilla sesseana (Ram\u00edrez) Rusby, Torreya 21: 47. 1921.Jarilla caudata is morphologically and phylogenetically closely related to Jarilla heterophylla. Their main distinguishing features are the fruits, which in Jarilla caudata can attain a length of 30 cm, having a smooth surface and 5 long, horn-like appendages (3\u20136 cm long). Other differences are given in the key. The species occurs in deciduous forests and fields of Baja California and central Mexico from 1500 to 1800 m above sea level.(Cerv. ex La Llave) Rusby, Torreya 21(3): 50. 1921.http://species-id.net/wiki/Jarilla_heterophyllaMocinna heterophyllaF. A. Carvalho 2240 . Cerv. ex La Llave, Reg. Trim. 1(3): 351. 1832. Type: Plate V of Ram\u00edrez, 1894 . Benth., Pl. Hartw. 288. 1849. Type: Mexico. Guanajuato, Leon, Papaya nana (Benth.) A. DC., Prodr. 15(1): 415. 1864.Jarilla nana (Benth.) McVaugh, Fl. Novo-Galiciana 3: 475. 2001.Jarilla caudata see under that species and in the key. Jarilla heterophylla occurs in oak forests, deciduous forests, and abandoned fields of central Mexico at 1500 to 2700 m above sea level.For differences from PageBreakPageBreakCarica caudata Brandegee, holotype:http://ucjeps.berkeley.edu/new_images/UC108333.jpg [accessed 30.07.2013]Carica cnidoscoloides Lorence & R. Torres, isotypes:http://www.tropicos.org/Image/11116 [accessed 11.08.2013]http://sweetgum.nybg.org/vh/specimen.php?irn=707429 [accessed 11.08.2013]Carica nana Benth., holotype: http://www.kew.org/herbcatimg/202388.jpg [accessed 30.07.2013]Jarilla chocola Standl., isotypes:http://apps.kew.org/herbcat/getImage.do?imageBarcode=K000500520 [accessed 11.08.2013]http://andor.nrm.se/kryptos/fbo/kryptobase/large/S-G-003001/S-G-3434.jpg [accessed 11.08.2013]Mocinna heterophylla Cerv. ex La Llave, epitype:http://herbaria.plants.ox.ac.uk/bol/caricaceae [accessed 11.10.2013]Mocinna heterophylla var. sesseana Ram\u00edrez, epitype:http://herbaria.plants.ox.ac.uk/bol/caricaceae [accessed 11.10.2013]"} +{"text": "Figures 1, 2, and 3 have been updated for better readability. Please see the correct figures here:http://plosone.org/corrections/pone.0064303.g001.cn.tifFigure 1: http://plosone.org/corrections/pone.0064303.g002.cn.tifFigure 2: http://plosone.org/corrections/pone.0064303.g003.cn.tifFigure 3: The affiliation for author Bruce Lee has been updated. The updated affiliation is: Public Health Computational and Operational Research (PHICOR) Group, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of AmericaThe affiliation for Leila A. Haidari, Diana L. Connor, Leslie E. Mueller, and Michelle M. Schmitz has been updated. The correct affiliation is:Public Health Computational and Operational Research (PHICOR) Group, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America"} +{"text": "AbstractOenothera fruticosa L. subsp. glauca (Michx.) Straley for one of the two recognized subspecies of O. fruticosa it was the correct name for this taxon; however, since that time the botanical code has changed so that now an autonym is treated as having priority over the name or names of the same date and rank that established it. This change means that since 1981 O. fruticosa subsp. glauca was no longer the correct name. The appropriate combination for it is made here as O. fruticosa L. subsp. tetragona (Roth) W.L. Wagner. Original material for the basionym, O. tetragona, is no longer extant so a neotype is designated.In 1978 when Straley adopted the name Oenothera fruticosa subsp. glauca (Michx.) Oenothera in the Flora of North America.The superfluous nature of the combination PageBreakOenothera sect. Kneiffia Munz and Oenothera tetragona Roth. In 1978 Straley\u2019s new combination was the correct name for the taxon; however, since that time the botanical code of nomenclature has changed so that an autonym is treated as having priority over the name or names of the same date and rank that established it. This change means that since 1981, when this rule was added , was definitely included by Straley in the synonymy of Oenothera fruticosa subsp. glauca, the correct name for this taxon must be the combination Oenothera fruticosa subsp. tetragona, which has not been previously made. The name Oenothera fruticosa subsp. glauca, although nomenclaturally superfluous (Art. 52.1), is not illegitimate and is here placed into synonymy.This rule is now Art. 11.6 of the current code of nomenclature , and it (Roth) W.L. Wagnercomb. nov.urn:lsid:ipni.org:names:77135763-1http://species-id.net/wiki/Oenothera_fruticosa_tetragonaOenothera tetragona Roth, Catal. Bot. 2: 39. 1800.Type. Grown in the garden of Wilhelm Koch, at Gnadau, near Barby, Germany, of American origin; no extant material located. Pennsylvania. Lancaster Co.: between Churchtown Rd. and Beartown, 6 September 1892, A.A. Heller 549 . Oe, tetragona, Herb. A. W. Roth.\u201d I contacted Robert Vogt at Berlin and there is currently no extant original material; however, he located a specimen grown from seeds provided by A. W. Roth \u201ce semin. Rothianis in h. bot. Wratislav. colui 1823,\u201c but there is no way to clearly connect this material with the original material used when Roth described the species. I have here selected a neotype that fits Roth\u2019s description and was considered to represent this entity in its narrowest interpretation. It was annotated by Munz for his 1937 revision and also by Straley for his 1978 revision.PageBreakOenothera glauca Michx., Fl. Bor.-Amer. (Michaux) 1: 224. 1803. Kneiffia glauca (Michx.) Spach, Hist. Nat. Veg. Phan. 4: 374. 1835. Oenothera fruticosa L. var. glauca (Michx.) H. L\u00e9v., Monogr. Onothera 107. 1902. Oenothera tetragona Roth subsp. glauca (Michx.) Munz, N. Amer. Fl., ser. 2, 5: 91. 1965. Oenothera fruticosa L. subsp. glauca (Michx.) Straley, Ann. Missouri Bot. Gard. 64: 403. 1978 .Type. Hab. in sylvis remotis et occidentalibus flumini Mississippi confinibus, versus regionem Illinoensium, 1787 or 1789, A. Michaux s.n. . According to"} +{"text": "AbstractMiconia densiflora Cogn. (1886) is a later homonym of Miconia densiflora (Gardner) Naudin (1851), but since we propose it as a taxonomic synonym of Miconia caudata (Bonpl.) DC. (1828), we do not provide a new name. The name Miconia longicuspis Miconia longicuspis Cogn. (1891) and we here propose its replacement by Miconia longicuspidata S.S. Renner & R. Goldenb.The name Melastomataceae, a pan-tropical family of about 3500 species. Among the databases that can be accessed at this site is \u201cMEL names,\u201d which deals with the ca. 13,278 names of Melastomataceae and Memecylaceae (= Melastomataceae subfamily Olisbeoideae) and provides information on recognized species, synonyms, and relevant literature. In the course of dealing with the 1497 names available for Miconia Ruiz & Pav., a genus of at least 1061 accepted species, we discovered two homonymy problems, resolved here. Since one of the homonyms is actually a heterotypic synonym of another species, a replacement name is only needed for one of these species. A comprehensive taxonomic treatment of Miconia is currently in preparation, as part of the PBI Miconieae project (sweetgum.nybg.org/melastomataceae/ ).The site S.S.Renner & R.Goldenb. nom. nov.urn:lsid:ipni.org:names:77111574-1http://species-id.net/wiki/Miconia_longicuspidataMiconia longicuspisMiconia longicuspis Cogn. in A.DC. & C.DC, Monog. Phan. 7: 850. 1891. (Replaced name) Herzog, Feddes Repert. Nov. Sp. 7: 64. 1909. Type: Bolivia. Cordillera de Santa Cruz: Cerro Ambor\u00f3, Cu\u00f1uc\u00fa, 600-1400 m, Oct 1907, T.Herzog 326 (holotype: Z!). Not Miconia longicuspis Herzog is a later homonym of Miconia longicuspis Cogn., a treelet from eastern Brazil in the mountains of Cu\u00f1uc\u00fa, Bolivia, in 1907. We have found no isotypes or type photos in G, JE, L, U, W, or WAG. This species most closely matches Miconia abbreviata Markgr., a widespread shrub that ranges from Bolivia throughout the Amazon basin to the Guianas, but differs in the much denser secondary venation. In Miconia abbreviata the secondaries are spaced at about 0.5\u20130.7 mm apart, in Miconia longicuspidata, only 2\u20133 mm apart. Theodor Herzog was an expert mountaineer and collector, who explored widely in Bolivia. During his two expeditions to that country in 1907/08 and 1910/11, he collected about 600 species of vascular plants. In 1910, Herzog not only explored the Cordillera Santa Cruz, where Miconia longicuspidata appears to be endemic, but also surveyed the Cordillera de Cocapata, a range of peaks near Cochabamba extending northwest for about 100 kilometers. A description of the flora of the Cordillera de Santa Cruz is given in n Brazil . Miconia(Bonpl.) DC., Prodr. 3: 187. 1828.http://species-id.net/wiki/Miconia_caudataMelastoma caudata Bonpl., Monogr. Melast. 1: 13. t. 7. 1807.(Basionym)Miconia densiflorasyn. nov. Type: COLOMBIA. Cauca: Popayan, Apr 1883, Lehmann 2798 (Isotype: US!). Non Miconia densiflora (Gardner) Naudin, Ann. Sc. Nat. Ser. 3, 16: 245, 1851, basionym Chaenopleura densiflora Gardner, Hook. Lond. Journ. Bot. 2: 349, 1843. (New synonym) Cogn., Bot. Jahrb. 8(1): 22, 1887 [1886]; et in A. DC. & C. DC. Monog. Phan. 7: 744, 1891, Miconia densiflora Cogn. is a later homonym of Miconia densiflora (Gardner) Naudin, which in turn is a taxonomic synonym of Miconia pusilliflora (DC.) Triana, a shrub from eastern Brazil DC. Miconia caudata has glandular-pubescent filaments, while Miconia densiflora has glabrous ones. However, all 15 specimens of Miconia caudata that we checked had completely glabrous filaments. A color photograph of Miconia densiflora\u2019s type is available at http://www.botany.si.edu/types.n Brazil . By cont"} +{"text": "A funding organization and two grants were incorrectly omitted from the Funding Statement. The Funding Statement should read: \"T.O.G. Tytgat and N.M. van Dam were partly funded by a VIDI grant, no. 864.02.001, of the Netherlands Organisation for Scientific Research (NWO) to N.M. van Dam. K.J.F. Verhoeven was funded by a VENI grant, no. 863.05.006, of the Netherlands Organisation for Scientific Research (NWO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\""} +{"text": "AbstractColeoptera: Carabidae) were sampled along rice field banks and in restored habitats, by means of pitfall traps. The area appeared as species-rich, compared to other anthropogenic habitats in the Po river pain. Most of the collected Carabids were species with a wide distribution in the Paleartic region, eurytopic and common in European agroecosystems. The assemblages were dominated by small-medium, macropterous species, with summer larvae. No endemic species were found. Species with southern distribution, rarely found north of the Po river, were also sampled. Amaralittorea is recorded for the first time in Italy.An entomological investigation was carried out in an agricultural area, mainly rice fields, of the Po river plain, located in the municipalities of Lacchiarella (MI) and Giussago (PV) . In 2009 and 2010, ground beetles ( In the last decades, intensification and mechanization of agricultural practices, introduced in order to maximise productivity, led to a decrease in habitat quality and landscape heterogeneity throughout European agroecosystems. Diffusion of monoculture, increased use of chemicals (i.e. pesticides and fertilizers) and removal of non-cropped areas, like small woodlots and hedges, caused a wide-scale loss of biodiversity .http://www.agricoltura.regione.lombardia.it).Recently, environmentally-friendly agronomic practices and creation of non-cropped habitats have been recognized as a potential solution to this dramatic decline of biodiversity and have become key aims of European Union\u2019s Common Agricultural Policy (CAP) and, as a consequence, of national and regional ones . In LombEven if agri-environment schemes (AESs) benefit some farmland species e.g., , gaps inThe aim of this research was to investigate the Carabid assemblages of an intensive agricultural area (mainly rice fields) subjected to environmental improvements since 1996, in particular the creation of buffer strips along paddy fields and the restoration of an area of \u200b\u200b150 ha.2 agricultural area, mainly cultivated with rice, located in north-western Italy, in the middle of the Po plain, approximately 13 km north from the city of Pavia, in the municipalities of Lacchiarella (MI) and Giussago (PV); barycentre 45\u00b017'38.63\"N, 09\u00b008'52.08\"E , sporadically with a row of poplar trees (Populuscanadensis);nks Fig. : charactbuffer strips . The first stands were planted in 2003 and, during the study period, strips were fully-developed into arboreal habitats . The last stands were planted in 2009 and, during the study period, strips were mostly covered by herbaceous vegetation ;ips Fig. : perimetrestored area , was divided from that of the forested areas and hedges .Ground beetles were sampled using plastic pitfall traps (62 mm in diameter and 70 mm deep) buried in the soil and filled with 50 ml of wine vinegar and a drop of detergent . PitfallAlong rice field banks, we placed a total of 60 traps from April to November 2009 and 68 traps from May to November 2010; along buffer strips, we positioned 56 traps from May to November 2009 and 2010; in the restored area, we placed 66 traps from July to November 2009 and from April to November 2010.Fauna Europaea was reported in brackets.A synthetic description of habitat preference, derived from aAD; totn) divided by sampling effort (US) for each sampling station:As for rice field banks and enhanced habitats, ground beetle abundances were expressed both as absolute frequency and as annual Activity Density aAD; , that istot / USDAa = nUS = \u03a3 us and us = trap * (gg/10), where trap is number of traps and gg is the number of days during which the traps were active in each sampling session and in the collection of the University of Pavia.Turanic-European. Open habitats, thermophilous. Macropterous, with winter larvae. Medium size. Spermatophagous.n = 2); recorded in arboreal restored habitats only.Uncommon north of the Po river. Rare in the study area Turanic-European-Mediterranean. Open habitats, halophilous. Macropterous, with summer larvae. Very small size. Spermatophagous.n = 1); recorded in herbaceous restored habitats only.Rare in the study area European. Paludicolous, ripicolous. Macropterous, with summer larvae. Very small size. Spermatophagous.n = 1); recorded in arboreal restored habitats only.Rare in the study area European-Mediterranean. Paludicolous, ripicolous. Macropterous, with summer larvae. Very small size. Spermatophagous.n = 18).Rare in the study area ; recorded in arboreal restored habitats only.Rare in the study area European. Paludicolous, ripicolous. Macropterous, with summer larvae. Small size.n = 107). Recorded in all habitat categories.Common in the study area Siberic-European (Holoartic). Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Predator.n = 8).Rare in the study area Siberic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Predator.n = 1); recorded in rice field banks only.Rare in the study area ; recorded in arboreal restored habitats only.Rare in the study area Siberic-European. Paludicolous, silvi-ripicolous. Macropterous, with summer larvae. Small size.n = 8); recorded in arboreal restored habitats only.Rare in the study area Paleartic (Holoartic). Open habitats, eurytopic. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 1180). Recorded in all habitat categories.Common in the study area Central Asiatic-European. Open habitats. Macropterous, with winter larvae. Small size. Zoospermatophagous.n = 2).Rare in the study area Asiatic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 7).Rare in the study area Siberic-European. Open habitats, eurytopic. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 10).Rare in the study area European. Open habitats, xerophilous. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 4).Rare in the study area ; recorded in herbaceous buffer strips only.Recorded with certainty for the first time in Italy . Rare inTuranic-European. Open habitats, xerophilous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 31).Rare in the study area ; recorded in rice field banks only.Rare in the study area Asiatic-European. Open habitats, eurytopic. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 203).Common in the study area European-Mediterranean. Open habitats, thermophilous. Macropterous, with summer larvae. Very small size.n = 7).Uncommon north of the Po river. Rare in the study area Paleartic. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Predator.n = 234). Recorded in all habitat categories.Common in the study area Asiatic-European. Open habitats, eurytopic. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 761). Recorded in all habitat categories.Common in the study area Asiatic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 798). Recorded in all habitat categories.Common in the study area Holoartic. Open habitats. Macropterous, with summer larvae. Small size. Predator.n = 11).Rare in the study area Turanic-European. Paludicolous, silvi-ripicolous. Macropterous, with summer larvae. Very small size. Predator.n = 1); recorded in arboreal buffer strips only.Rare in the study area Holoartic. Open habitats, hygrophilous. Macropterous, with summer larvae. Very small size. Zoospermatophagous.n = 866). Recorded in all habitat categories.Common in the study area ; recorded in herbaceous buffer strips only.Rare in the study area . Recorded in all habitat categories.Common in the study area .Rare in the study area .Rare in the study area .Rare in the study area European-Mediterranean. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Predator.n = 372).Common in the study area Turanic-European. Open habitats, xerophilous. Macropterous, with winter larvae. Very small size. Spermatophagous.n = 2); recorded in herbaceous buffer strips only.Rare in the study area European-Mediterranean. Open habitats, xerophilous. Pteridimorphic, with winter larvae. Medium size. Predator.n = 8).Rare in the study area Paleartic. Open habitats, xerophilous. Pteridimorphic, with winter larvae. Small size. Predator.n = 177).Common in the study area Central Asiatic-European. Open habitats, xerophilous. Macropterous, with summer larvae. Large size. Predator.n = 115).Common in the study area . Paludicolous, silvi-ripicolous. Pteridimorphic, with summer larvae. Large size. Predator.n = 64).Common in the study area Central Asiatic-European. Paludicolous. Macropterous, with summer larvae. Medium size.n = 123). Recorded in all habitat categories.Common in the study area Paleartic. Paludicolous. Macropterous, with summer larvae. Medium size. Predator.n = 4).Rare in the study area Paleartic. Paludicolous. Macropterous, with summer larvae. Large size. Predator.n = 62). Recorded in all habitat categories.Common in the study area ; recorded in rice field banks only.Rare in the study area Turanic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size.n = 1); recorded in rice field banks only.Rare in the study area Asiatic-European (Holoartic). Open habitats, hygrophilous. Pteridimophic, with summer larvae. Small size. Predator.n = 28). Recorded in all habitat categories.Rare in the study area Turanic-European-Mediterranean. Open habitats. Macropterous, with summer larvae. Small size.n = 161).Common in the study area European-Mediterranean. Open habitats, xerophilous. Macropterous, with summer larvae. Medium size.n = 3).Uncommon north of the Po river. Rare in the study area Asiatic-European. Open habitats. Macropterous, with winter larvae. Large size.n = 5); recorded in herbaceous buffer strips only.Rare in the study area Afrotropical and Paleartic. Paludicolous. Macropterous, with summer larvae. Small size. Predator.n = 1); recorded in arboreal buffer strips only.Rare in the study area Asiatic-European (Holoartic). Open habitats. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 372).Common in the study area ; recorded in rice field banks only.Rare in the study area Paleartic. Open habitats. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 331). Recorded in all habitat categories.Common in the study area .Uncommon north of the Po river. Rare in the study area European. Open habitats, xerophilous. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 15).Rare in the study area Paleartic. Open habitats. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 1396). Recorded in all habitat categories.Common in the study area European. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 80). Recorded in all habitat categories.Common in the study area .Uncommon north of the Po river. Common in the study area ; recorded in rice field banks only.Rare in the study area .Common in the study area Asiatic-European. Open habitats. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 180). Recorded in all habitat categories.Common in the study area Paleartic. Open habitats, xerophilous. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 177).Common in the study area Asiatic-European. Open habitats, eurytopic. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 97).Common in the study area Siberic-European. Paludicolous, silvi-ripicolous. Macropterous, with summer larvae. Medium size. Predator.n = 263); recorded in arboreal restored habitats only.Common in the study area Siberic-European. Paludicolous, silvi-ripicolous. Macropterous, with summer larvae. Medium size.n = 50); recorded in arboreal restored habitats only.Common in the study area Paleartic (Holoartic). Open habitats, eurytopic. Pteridimorphic, with summer larvae. Very small size. Predator.n = 49).Common in the study area Siberic-European. Open habitats, eurytopic. Pteridimorphic, with summer larvae. Very small size.n = 225). Recorded in all habitat categories.Common in the study area Turanic-Mediterranean. Open habitats. Macropterous, with summer larvae. Very small size.n = 2).Rare in the study area Holoartic. Open habitats, eurytopic. Pteridimorphic, with summer larvae. Very small size.n = 111).Common in the study area Turanic-European. Open habitats, hygrophilous. Macropterous, with winter larvae. Medium size. Predator.n = 1); recorded in arboreal restored habitats only.Rare in the study area Siberic-European. Paludicolous. Macropterous, with summer larvae. Small size. Predator.n = 15).Rare in the study area Central Asiatic-European-Mediterranean. Open habitats, xerophilous. Pteridimorphic, with winter larvae. Small size. Spermatophagous.n = 1); recorded in herbaceous buffer strips only.Rare in the study area Turanic-European. Open habitats, xerophilous. Macropterous, with winter larvae. Small size. Spermatophagous.n = 2); recorded in rice field banks only.Rare in the study area European. Open habitats. Macropterous, with winter larvae. Medium size. Spermatophagous.n = 1); recorded in herbaceous restored habitats only.Rare in the study area European. Open habitats. Macropterous, with winter larvae. Small size. Spermatophagous.n = 3); recorded in arboreal restored habitats only.Rare in the study area Siberic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size.n = 1); recorded in herbaceous buffer strips only.Rare in the study area European-Mediterranean (Holoartic). Ripicolous. Macropterous, with summer larvae. Small size.n = 1); recorded in arboreal restored habitats only.Rare in the study area Turanic-Mediterranean. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size.n = 190). Recorded in all habitat categories.Common in the study area S-European. Open habitats, thermophilous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 65).Common in the study area S-European. Open habitats, thermophilous. Macropterous, with summer larvae. Small size.n = 18).Uncommon north of the Po river. Rare in the study area E-Mediterranean. Open habitats, thermophilous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 11).Uncommon north of the Po river. Rare in the study area Siberic-European. Silvi-ripicolous. Ptedirimorphic, with winter larvae. Small size. Predator.n = 314).Common in the study area European-Mediterranean. Open habitats, hygrophilous. Macropterous, with summer larvae. Very small size. Predator.n = 28). Recorded in all habitat categories.Rare in the study area Asiatic-European. Open habitats, eurytopic. Macropterous, with summer larvae. Medium size. Zoospermatophagous.n = 6127). Recorded in all habitat categories.Dominant in the study area Asiatic-European. Open habitats, hygrophilous. Macropterous, with summer larvae. Medium size. Predator.n = 1025). Recorded in all habitat categories.Common in the study area Paleartic. Open habitats, eurytopic. Macropterous, with winter larvae. Medium size.n = 286). Recorded in all habitat categories.Common in the study area Paleartic (Holoartic). Open habitats, eurytopic. Macropterous, with winter larvae. Medium size. Zoospermatophagous.n = 12 626). Recorded in all habitat categories.Dominant in the study area W-Paleartic. Paludicolous, silvi-ripicolous. Macropterous, with summer larvae. Medium size.n = 25). Recorded in all habitat categories.Rare in the study area Asiatic-European. Open habitats, xerophilous. Macropterous, with summer larvae. Medium size. Predator.n = 1); recorded in rice field banks only.Uncommon north of the Po river. Rare in the study area Holoartic. Eurytopic. Pteridimorphic, with winter larvae. Large size. Predator.n = 869). Recorded in all habitat categories.Common in the study area Asiatic-European. Silvicolous, hygrophilous. Pteridimorphic, with winter larvae. Large size. Predator.n = 1292). Recorded in all habitat categories.Common in the study area Paleartic. Eurytopic, hygrophilus. Pteridimorphic, with summer larvae. Medium size. Predator.n = 34).Rare in the study area Asiatic-European. Silvi-ripicolous. Pteridimorphic, with summer larvae. Small size. Predator.n = 263). Recorded in all habitat categories.Common in the study area Paleartic. Eurytopic, hygrophilous. Macropterous, with summer larvae. Small size. Predator.n = 160). Recorded in all habitat categories.Common in the study area Afrotropical-Mediterranean. Open habitats, hygrophilous. Macropterous, with summer larvae. Very small size.n = 4).Rare in the study area Paleartic. Paludicolous. Macropterous, with summer larvae. Small size. Zoospermatophagous.n = 5).Rare in the study area Turanic-European-Mediterranean. Open habitats, hygrophilous. Macropterous, with summer larvae. Small size.n = 605). Recorded in all habitat categories.Common in the study area European-Mediterranean. Eurytopic. Macropterous, with summer larvae. Very small size. Predator.n = 190).Common in the study area Siberic-European. Silvicolous. Pteridimorphic, with summer larvae. Very small size. Predator.n = 8).Rare in the study area Asiatic-European. Silvicolous, hygrophilous. Pteridimorphic, with winter larvae. Small size. Zoospermatophagous.n = 1); recorded in arboreal restored habitats only.Rare in the study area Turanic-European-Mediterranean. Eurytopic. Pteridimorphic, with winter larvae. Very small size. Predator.n = 7).Rare in the study area , 6 species only in herbaceous buffer strips , 2 species only in arboreal buffer strips , 2 species only in herbaceous restored habitats and 11 species only in arboreal restored habitats . Poeciluscupreus and Pseudoophonusrufipes consituted about 55% of the capture with 18 753 individuals.Overall, we collected 34,108 individuals belonging to 98 carabid species. We recorded 65 species in rice field banks, 73 species in buffer strips and 78 in restored habitats. Eight species were found only in rice field banks . About 80% of the collected species had larvae that develop during summer, without dormancy (i.e. were spring breeders) and 18.4% were species with winter larvae, that grow slowly with compulsory dormancy (i.e. were autumn breeders). Cicindelacampestris was the only species with poliennal larvae. Macropterous and pteridimorphic species were 82.7% and 17.3% respectively; we didn\u2019t find any strictly brachypterous species.The collected species belonged to 17 chorotypes Fig. , groupedAlso rice field banks, buffer strips and restored habitats, analyzed separately, were dominated by Holoartic, medium-small, winged species, with summer larvae Table ; speciesLebiinae and Bembidinae. Nevertheless, the area resulted species-rich, especially when you consider that it is not placed inside a riverine corridor and when you compare the species number with that recorded in other anthropogenic habitats of the Po plain: 60-70 species in rye, oat and fallow fields . Species number could be slightly underestimated because of the sampling method which is not very well suited for some taxa as w fields ; 48 specw fields ; 55 specw fields ; 60 specw fields ; 60 specw fields .Most of the collected carabids, both in the whole area and in each habitat categories, were species with a wide distribution in the Paleartic region, eurytopic and common in European agroecosystems. The assemblages were dominated by small-medium, macropterous species, with summer larvae; we didn\u2019t find any endemism.Abaxcontinuus Ganglbauer 1891, very common in woods of the Lombardy plain), because of the absence of ecological corridors connecting woodlots with forest remnants . In fact, species unable to disperse by flight were prevented to colonize these stands . They are not reported in the historical catalogue of The most interesting aspect of this Carabid coenosis is the presence of several species with southern distribution, quite common in clay soil on the right bank of the Po river, and known only in few stations north of the Po river. Among these species, we list Brachinusplagiatus, an uncommon halophilous species. Moreover Amaralittorea, an Asiatic-European distribution species, has been recorded with certainty for the first time in Italy (We underline also the presence of in Italy ."} +{"text": "Produced in collaboration with the International Council of Ophthalmology (ICO).Test your understanding of the concepts covered in this issue and discuss any points of interest with your manager or a colleague. 1a. True. b. False. Governments must cover some of the costs or organise health insurance, as in Ghana. c. False. Some patients will pay more for value-added services. d. True.2a. False. Bulk buy medicines and consumables yearly or quarterly. b. True. c. True. You can start on paper. d. True."} +{"text": "Pseudomonas spp. sensu Gardan et alii, and their phylogenetic relationships using maximum likelihood and Bayesian approaches. The results demonstrate the existence of a well demarcated genomic cluster that includes strains classified as P. avellanae, P. syringae pv. theae, P. s. pv. actinidiae and one P. s. pv. morsprunorum strain all belonging to the single species P. avellanae. In addition, when compared with P. avellanae, five strains of P. s. pv. tomato, including the model strain DC3000, and one P. s. pv. lachrymans strain, appear as very closely related to P. avellanae, with ANI values of nearly 96% as confirmed by the TETRA analysis. Conversely, one representative strain, previously classified as P. avellanae and isolated in central Italy, is a genuine member of the P. syringae species complex and can be defined as P. s. pv. avellanae. Currently. The core and pan genomes of P. avellanae species consist of 3,995 and 5,410 putative protein-coding genes, respectively.The circumscription of bacterial species is a complex task. So far, DNA-DNA hybridization (DDH), 16S rRNA gene sequencing, and multiocus sequence typing analysis (MLSA) are currently the preferred techniques for their genetic determination. However, the average nucleotide identity (ANI) analysis of conserved and shared genes between two bacterial strains based on the pair-wise genome comparisons, with support of the tetranucleotide frequency correlation coefficients (TETRA) value, has recently been proposed as a reliable substitute for DDH. The species demarcation boundary has been set to a value of 95-96% of the ANI identity, with further confirmation through the assessment of the corresponding TETRA value. In this study, we performed a genome-wide MLSA of 14 phytopathogenic pseudomonads genomes, and assessed the ANI and TETRA values of 27 genomes, representing seven out of the nine genomospecies of Corylusavellana L.) was first observed in northern Greece during the 1970s. Based on biochemical and nutritional tests, and a host range pathogenicity test, the bacterium responsible for the decline was named Pseudomonas syringae pv. avellanae and the disease was defined as bacterial canker of hazelnut [P. s. pv. avellanae [P. avellanae [P. avellanae as a distinct genomospecies, namely genomospecies 8, within the P. syringae species complex and some other phytopathogenic pseudomonads [P. s. pv. theae [P. s. pv. actinidiae, as subsequently pointed out [P. avellanae populations found in Greece and Italy, and these differences were considered to be representative of the variability of the species. Therefore, two different lineages belonging to the same species were recognized and retained as originating separately [A rapid and destructive decline of cultivated hazelnut analysis (MLSA), based on fragments of the housekeeping genes ogroup 2 . This re species ,13,14,15 species and refelogroups ,18,19,20The circumscription of bacterial species is indeed a difficult task ,22,23. TPseudomonas spp. representing seven out of nine genomospecies sensu Gardan et al. [Pseudomonas lineages associated with hazelnut bacterial canker in Greece and Italy , and b) to verify their genomic relationship within the genomospecies 8 and other genomospecies of phytopathogenic pseudomonads.In this study, in addition to an MLSA based on seven housekeeping genes and maximum likelihood and Bayesian approaches, a genome wide phylogenetic analysis and consensus networks were performed with 14 genomes of phytopathogenic pseudomonads. Moreover, we analyzed the genome of 29 strains belonging to n et al. using thP. avellanae species that also includes strains classified as P. syringae pv. theae, P. s. pv. actinidiae and one P. s. pv. morsprunorum strain. As the TETRA values confirmed the findings all such strains could putatively belong to P. avellanae. In addition, when compared to P. avellanae, five strains of P. s. pv. tomato, including the model strain DC3000, and one P. s. pv. lachrymans strain, showed ANI values very close to 96% which was confirmed by the TETRA analysis. Finally, one representative strain, previously classified as P. avellanae sensu Janse et al. [P. syringae species complex and can be identified as P. s. pv. avellanae.We revealed the existence of a well-demarcated e et al. and isolPseudomonas strains, namely P. avellanae BPIC631 (type-strain of the species), P. avellanae CRAFRUEC1, P. syringae pv. theae NCPPB2598 (type-strain of the pathovar) and P. s. pv. syringae CRAFRU11 and CRAFRU12 (isolated from Cavellana. ). The genome size of the five strains was within the range of the previously sequenced and published P. syringae draft genomes . The main genomic features of the draft genomes are shown in P. avellanae BPIC631=ATDK00000000; P. avellanae CRAFRUEC1=ATLL00000000; P. s. pv. theae NCPPB2598=ATDJ00000000; P. s. pv. syringae CRAFRU11=ATSU00000000 and P. s. pv. syringae CRFRU12=ATSV00000000. The bacterial strains and the respective accession numbers of their genomes utilized in this study are shown in We generated second generation sequence data from five argS, dnaQ, gltA, gyrB, recA, rpoB and rpoD of 27 phytopathogenic pseudomonads representative of seven genomospecies sensu Gardan et al. [Pseudomonas spp. used as outgroups are shown in Pseudomonas members of genomospecies 2 and 3 and 8 in addition to P. s. pv. morsprunorum M302280 putatively belonging to genomospecies 3. The significance of such clustering is very high in both trees. The strains representative of the species P. s. pv. oryzae, Pviridiflava. and Pcannabina. pv. alisalensis resulted well distinct from the above described clusters ; b) members of genomospecies 2 (P. s. pv. lachrymans) and 3 (P. s. pv. tomato); and c) members of genomospecies 3 (P. s. morsprunorum) and 8 . Pcannabina. pv. alisalensis BS91 (genomospecies 9) clustered separately. The relatively long distances between the clusters and the high bootstrap values support the notion that the above-described clusters represent distinct evolutionary lineages.The ML tree of the concatenated protein sequences of 1,920 genes in 14 phytopathogenic pseudomonads representative of five genomospecies sensu Gardan et al. [This concatenation includes a large fraction of the genome thus providing sequences that are long enough to overcome sampling error. Nonetheless, the robustness of the phylogenetic reconstruction might not be easily evaluated even with 100% non parametric bootstrap support , as the P. s. pv. morsprunorum, P. avellanae and P. s. pv. actinidiae/P. s. pv. theae is different from that displayed in the ML tree of With reference to the strain composition of the individual clusters, we observed a limited, yet detectable presence of contradictory phylogenetic signals associated with complex evolutionary histories of the individual strains. The lack of full congruence of the individual gene phylogenies, likely due to the role that horizontal DNA transfer from other relatives had in shaping the evolution of the individual strains, was additionally highlighted by a consensus network. Pseudomonas spp. representative of seven of the nine genomospecies described by Gardan et al. after DDH assessment [Pseudomonas spp., namely P. fluorescens A506 and Pputida. UW4 used as outgroups, were cross-compared to reveal their total similarities in terms of the amount of sequence identity. The ANI value calculations, based on the MUMmer alignment of each sequence pair, are reported in The five newly sequenced genomes, together with those of another 22 phytopathogenic sessment , and twoPseudomonas avellanae species , with P. s. pv. tomato , P. s. pv. lachrymans (M302278) and P. s. pv. avellanae (CRAPAV013). The figure shows the ANI analysis values of P. avellanae, P. s. pv. theae, and P. s. pv. actinidiae (genomospecies 8) displayed ANI values that were consistently higher than 97.5% in any reciprocal comparison. The four P. s. pv. actinidiae strains showed ANI values that were always higher than 99% in intrapathovar comparison. Remarkably, P. s. pv. morsprunorum M302280 showed ANI values that were consistently higher than 97.8% when compared to the strains of genomospecies 8. In addition, P. s. pv. tomato strains DC3000, NCPPB1108, T1, Max13 and K40 and P. s. pv. lachrymans M302278 showed ANI values comprised between 95 and 96% in any reciprocal comparison with strains of genomospecies 8 and P. s. pv. morsprunorum M302280 to 98.6% (P. s. pv. aceris M302273 versus P. s. pv. syringae B728a) for strains belonging to genomospecies 1. The strains representative of genomospecies 4, 6, and 9, namely P. s. pv. oryzae 1.6, Pviridiflava. UASWS0038 and P. c. pv. alisalensis BS91, respectively and the outgroups P. fluorescens A506 and Pputida. UW4 showed ANI values lower than 88.2% when reciprocally compared to the other genomospecies strains to 11.9% (P. s. pv. morsprunorum 302280). The pan genome of the species, based on the seven strains here assessed, would seem similar, in terms of CDSs number, to that of the P. syringae species complex which was inferred with 19 strains infecting a vast array of plant species and consisting of 12,829 CDSs [The core genome consists of the number of genes found in all the sequenced strain genomes of a species, whereas the pan genome comprises the sum of the core genome and genes of the \u201cflexible\u201d genome ,30. We ang genes . Each stng genes . The ove829 CDSs .P. avellanae species based on the complete dataset of effector proteins identified in 19 P. syringae as assessed by Baltrus et al. [hopM1, present in all seven strains of P. avellanae, provides evidence for the pathogenic differentiation of the strains of the P. avellanae species complex from P. s. pv. tomato and P. s. pv. lachrymans. In fact, Baltrus et al. [hopM1 locus that split the strains of clade I into two clearly separated groups: P. s. pv. actinidiae M302091-P. s. pv. morsprunorum M302280 and P. s. pv. tomato DC3000-P. s. pv. lachrymans 106.A comparison of the effector repertoires of the seven strains of s et al. , reveales et al. found a m [P. syringae pathovars, delineated a robust classification based on nine discrete genomospecies. However, according to the international taxonomic rules, a genomospecies should be named formally only when phenotypic characters are available to differentiate them [Pseudomonascannabina, Ptremae. ). Consequently, most of such genomospecies still have to formally be described.The technical and conceptual definition of bacterial species continues to be uncertain representing a challenging task ,33. Currm . Howeverm . A technm . Within m , by perfate them . Since Gate them did not However, several studies have shown that the sequencing of a single, highly conserved gene, such as the 16S rRNA gene, fails to intercept the true genome-wide divergence between two strains ,37,38. MThe advent of genomic has begun to provide complete or draft bacterial genomes that can easily be retrieved from public databases. Based on the opportunity offered by the availability of large gene datasets, MLSA could be extended to a relevant part of the genome, minimizing the gene selection bias and sampling error ,40. In tP. avellanae, BPIC631 (type-strain), the causal agent of hazelnut bacterial canker in Greece, P. syringae pv. theae NCPPB2598, (type-strain) the causal agent of bacterial tea shoot blight in Japan and P. syringae pv. actinidiae (type-strain and other three strains), the causal agents of Actinidia spp. bacterial canker worldwide, are included in the boundary of the species. According to a DDH study performed by Gardan et al. on P. syringae pathovars and on a subsequent molecular and genomic typing, these phytopathogens all belong to genomospecies 8 [P. s. pv. morsprunorum strain, namely M302280, included in our analysis, showed ANI and TETRA values and phylogenetic grouping that consistently suggested its inclusion within the species P. avellanae. However, this pathovar shows an evident genetic variability and two races of the pathogen (race 1 and 2) are clearly distinguishable by means of classical biochemical tests and repetitive-sequence PCR and MLSA [P. s. pv. morsprunorum strains, namely CFBP2116 (race 1) and NCPPB2995 (race 2 and the pathotype strain of the pathovar), into genomospecies 2 and 3, respectively. Unfortunately, we do not know whether M302280 corresponds to one of these strains. In addition, the transfer of P. s. pv. morsprunorum as a whole into P. avellanae requires further studies using a larger number of representative strains.We clarified the taxonomic position of a group of strains that are genomically very closely related to each other, constructing a tight and coherent phylogenetic cluster showed ANI values higher than 97.5% and high TETRA scores in all reciprocal comparisons; therefore these strains should belong to the same species. The presence of more than one single and well-characterized biological entity within the species revealed the existence of a complex and phytopathologically diversified species. In fact, we found that pecies 8 . Of noteand MLSA ,45,46. TPseudomonas strain, isolated from a hazelnut tree showing bacterial canker disease in central Italy, which was originally identified as P. syringae pv. avellanae [P. avellanae [P. avellanae species as outlined in this paper but rather to the genomospecie 1 sensu Gardan et al. [P. syringae species complex. In fact, genome analyses indicated that this strain is phylogenetically strictly related to other P. s. pv. syringae strains, with ANI values higher than 95% resulting from the comparison with P. syringae pvs syringae B728a, aceris M302273 and pisi 704B. Thus, our study also partly reconciles previous investigations based on MLSA that actually treated the two P. avellanae lineages as belonging to separate phylogroups of the P. syringae species complex [P. avellanae, whereas CRAPAV013=ISPaVe013 and, most probably the related strains isolated from hazelnut trees in central Italy, are genuine P. syringae pv. avellanae strains. It should be stressed that in central Italy have been repeatedly isolated, from hazelnut trees showing symptoms of bacterial canker, both P. avellanae and P. s. pv. avellanae as revealed in the present study and in previous paper [Our study also clearly noted that one ellanae , and latvellanae does notn et al. of the P complex . Based o complex should nus paper .rpoD, or on MLSA of concatenated nucleotide or protein sequences, recently noted the close relationships between P. avellanae BPIC631, P. s. pv. theae NCPPB2598, different strains of P. s. pv. actinidiae, and P. s. pv. morsprunorum NCPPB2995 and M302280 [The phylogenetic analysis performed using with wide-genome data of 1,920 proteins and using ML and a Bayesian approaches with the assessment of both concatenated nucleotide and amino acid sequences belonging to seven housekeeping genes, were all congruent with the ANI and TETRA analysis and with the discussed results. Additionally, recent studies, based on a single housekeeping gene, namely M302280 ,20,47.P. avellanae cluster. The effector hopM1, which is present in all seven strains differentiated the P. s. pv. actinidiae-P. s. pv. morsprunorum strains from the P. s. pv. tomato-P. s. pv. lachrymans strains due to a putative recombination event occurred in the effector locus [Within this context, the assessment of type III effector protein repertoires provided interesting perspectives. In fact, we found both a putative core repertoire of 14 effector proteins and unique effectors for each of the four pathovars in the or locus . It is tP. s. pv. tomato (genomospecies 3), including DC3000, and one strain of P. s. pv. lacrhymans (genomospecies 2) with the strains of the P. avellanae In fact, all these strains showed ANI values very close to 96%. Richter and Rossell\u00f3-M\u00f3ra [P. s. pv. tomato and P. s. pv. lachrymans strains are embedded within the strains of the P. avellanae species. In this regard, other studies have outlined the close phylogenetic relationships between such strains with the strains of P. avellanae species [P. avellanae species and strains of genomospecies 3 and P. s. pv. lachrymans can be inferred through the comparison of the core/pan genomes of 19 P. syringae strains by Baltrus et al. [P. s. pv. actinidiae 302091, P. s. pv. morsprunorum 302280, P. s. pv. tomato DC3000 and T1, and P. s. pv. lachrymans 106 clustered apart from the other two P. syringae clades. In addition, this clade, composed by a few strains, contained the highest number of core genes in comparison to the core genomes of the wo larger clades. Whether P. s. pv. tomato and P. s. pv. lachrymans are divergent members of P. avellanae or whether they represent a closely related species deserve further evaluation.The ANI and TETRA analyses, in strict agreement with the phylogenetic analyses, also indicated the close relationships of the five strains of ll\u00f3-M\u00f3ra establis species ,20,47. As et al. . These aP. avellanae. A nomenclatural revision of this taxon should be postponed for the availability of further genomic data that could clarify the position of the strains currently classified as P. s. pv. morsprunorum. The revision should be also elaborated within the overall context of the nomenclatural revision of the P. syringae species complex, to coherently address the issued posed by the strict relationships between the strain clusters. Due to the priority rules according to the International Code of Nomenclatura of Bacteria [P. syringae species complex may result in the need for name changes that may be confounding and should, therefore, be attempted with caution [In conclusion, this study demonstrated the existence of a distinct cluster of strains that represent the nucleus of the species Bacteria ,49, the caution .P. avellanae BPIC631 and CRAFRU EC1, P. s. pv. theae NCPPB2598, P. s. pv. syringae CRAFRU11 and CRAFRU12 cultures grown in KB broth DNA using a Wizard DNA purification kit following the manufacturer\u2019s instructions. The identification of P. avellanae CRAFRUEC1 and P. s. pv. syringae CRAFRU 11 and 12 was achieved using well established techniques [Bacterial genomic DNA was extracted from 1 ml of overnight chniques . DNA wasde novo (i.e. without using a reference genome) assembly option of the CLC genomic workbench by setting the default parameters. Contigs sequences were scanned for ORFs by GLIMMER, version 3.02[P. s. pv. tomato DC3000 , P. s. pv. phaseolicola 1448A , and P. s. pv. syringae B728a . The putative proteins were annotated against the RefSeq database using a PERL script for recursive BLASTX searches. Additional genome sequence analyses was performed with the aid of the software packages MUMmer 3.0 [ad hoc PERL scripts were developed to assist the comparison of genome sequence drafts and their putative protein complement with respect to P. avellanae, P. s. pv. theae and P. s. pv. syringae strains, and P. s. pv. tomato DC3000, P. s. pv. phaseolicola 1449A and P. s. pv. syringae B728a.Paired reads were assembled into contigs using the sion 3.02. which hMmer 3.0 and MAUVMmer 3.0 . SeveralP. fluorescens A506 and Pputida. UW4 were included into the assessment as outgroups and tetranucleotide frequency correlation coefficients (TETRA) were performed with the software JSpecies . The anasee also . ANI wassoftware .Pseudomonas spp strains, we built five phylogenetic trees. P. fluorescens A506 and Pputida. UW4 strains were used as outgroups. Maximum Likelihood (ML) and the Bayesian method analysis were performed with both nucleotide and amino acids sequences using seven housekeeping genes , for a total of 6,579 nt and 2,193 aa, respectively. ML analysis was inferred with with PhyML version 3.0 [http://tree.bio.ed.ac.uk/software/figtree/). In addition, a split network tree, based on concatenation of 6,579 nucleotides from 27 phytopathogenic pseudomonads and P. fluorescens A506 and Pputida. UW4 strains as outgroups, was built using the neighbor-joining (NJ) algorithm with the Hamming distance method, obtained using the Splits-Tree software [In order to evaluate the evolutionary relationships of the 27 phytopathogenic sion 3.0 , with 1,sion 3.0 and Protsion 3.0 . GTR + Iad hocPerl scripts. First, the predicted protein sequences of all genomes were analyzed for the identification superfamilies of homologs by a procedure based on reciprocal smallest distance algorithm [P. avellanae species. The trees from each individual DNA sequence alignments were obtained by recursively running PhyML [SplitTree4, using a mean network construction [A data set containing ortholog alignment was prepared using a multistep procedure based on several lgorithm . Subsequlgorithm , allowedng PhyML using LCtruction . These ntruction .PhyML [SplitTree4 [taxa is equal to the length of the shortest path connecting them. It is therefore capable of highlighting taxa relationships that are not tree-like.The putatively coded protein sequences were also concatenated to obtain a single large alignment that was submitted to ML analysis with PhyML using LClitTree4 . Split nlitTree4 was complitTree4 and is dP. avellanae. Concerning the pan genome, for the ORFs assembly we have selected the families as obtained from the genome wide analysis and additionally showing > 60% length hit.The data set containing ortholog alignments, prepared as described above in the section \u201cgenome wide phylogenetic analysis\u201d, was used for the selection of shared versus specific genes among the seven strains here described as Figure S1Pseudomonas species and P. syringae pathovars.Bayesian phylogenetic tree showing relationships among representative strains of phytopathogenic The phylogenetic tree was constructed using 6,579 concatenated nucleotides of seven housekeeping genes with bootstrap values shown at the nodes. Strain members of genomospecies 8 (P. avellanae) sensu Gardan et al. [P. s. pv. morsprunorum M302280, are shown in red, whereas strain members of genomospecies 2 (P. s. pv. lachrymans M302278) and 3 (P. s. pv. tomato) are in blue. P. fluorescens A506 and Pputida. UW4 were included as outgroups. The interior node values of the tree are clade credibility values based on the posterior credibility values produced by MrBayes.(TIF)Click here for additional data file.Figure S2Pseudomonas species and P. syringae pathovars.Phylogenetic relationships among representative strains of phytopathogenic The phylogenetic tree was constructed using 2,193 concatenated amino acid sequences with bootstrap values greater than 65 per cent (1000 replicates) shown at the nodes. The phylogenetic relationships were inferred using the maximum likelihood (ML) method and the Dayoff + G + F as the best model with the PHYLIP package. Strain members of genomospecies 8 (P. avellanae) sensu Gardan et al. [P. s. pv. morsprunorum M302280, are shown in red, whereas strain members of genomospecies 2 (P. s. pv. lachrymans M302278) and 3 (P. s. pv. tomato) are in blue. P. fluorescens A506 and Pputida. UW4 were included as outgroups.(TIF)Click here for additional data file.Table S1Pseudomonas strains belonging to genomospecies 1, 2, 3, 4, 6, 8 and 9 sensu Gardan et al. [P. fluorescens A506 and Pputida. UW4 as outgroups.Average nucleotide identity (ANI) values calculated between genomes of 20 representative n et al. , and P. Values higher than 95% are in boldface. The ANI values of P. avellanae species strains and P. s. pv. tomato DC3000 and P. s. pv. lachrymans M32278 are also pointed out in grey.(DOCX)Click here for additional data file."} +{"text": "The Reference for the image used in Figure 1A was incorrectly omitted. The reference is: \"Kingdon, J. 1971. East African Mammals: An Atlas of Evolution in Africa. Vol. I: Primates. Academic Press, London, 446 pp.\""} +{"text": "PLoS ONE 5(8): e12221. doi:10.1371/journal.pone.0012221The name of the first author is incorrectly given in the author byline. The correct name is: Sangeetha V.M. In addition, the first author\u2019s name is incorrectly represented in the Citation. The correct Citation is: V.M. S, Kale VP, Limaye LS (2010) Expansion of Cord Blood CD34"} +{"text": "In the Materials and Methods, the paragraph after Equation 3 contains several errors that were introduced during production. The third sentence of that paragraph should read \"the nearby voxels include , , , , , , , and .\"http://plosone.org/corrections/pone.0080713.e000.cn.tifIn the fifth sentence of that paragraph, half of the equation is missing. Please see the full equation here: http://plosone.org/corrections/pone.0080713.t001.cn.tifThere are also errors in Table 1. Please refer to the corrected Table 1 here:"} +{"text": "Polypterus retropinnis and P. mokelembembe, were misidentified in our original study [P. retropinnis demonstrated that it consisted of both P. retropinnis and P. mokelembembe [After re-evaluation, we have determined that two species, al study . The ovelembembe . TherefoP. retropinnis is in fact referring to P. mokelembembe, and vice versa.We note that any reference in the original text to P. endlicheri congicus and P. e. endlicheri were switched. We have corrected this below , the symbols for low Fig. . Because"} +{"text": "Amalaki Rasayana is a unique formulation mentioned in Charaka Samhita . The main aim of the present study was to undertake comparative evaluation of three different preparations of Amalaki (Phyllanthus emblica), to find out which of the three forms provides good anti-ulcer effect and what would be the probable mechanism of action.Amalaki Rasayana samples were tested for their anti-ulcer effect in Charles Foster\u2019s strain albino rats and divided into 4 groups: Control and Ordinary Amalaki Rasayana (O.A.R.), Freeze Dried Amalaki Rasayana (F.D.A.R.), Freeze Dried Amalaki Churna (F.D.A.C.) . Gastric ulcer was induced by oral administration of aspirin (400 mg/kg) and with ligation of the pyloric end of the stomach . After collection of the gastric juice, the stomach was opened along the greater curvature and the inner surface was carefully observed. A subjective score was assigned (S. K. Kulkarni & R. K. Goel 1996). The volume of gastric juice was measured, and the total and free acid , total carbohydrate , total protein , and peptic activity in the gastric juice were estimated .All three samples of Amalaki Rasayana did not exhibit significant anti-ulcer activity at the dose levels studied. F.D.A.R. had no effect, but a 12.05% decrease was observed in the F.D.A.C. administered group, suggesting that among the three samples only F.D.A.C. had moderate anti-ulcer activity. The drug, at the dose level, does not seem to be acting by enhancing gastric mucosal secretion. However, it produced a moderate decrease in the total acidity (54.26%), suggesting that at least part of the observed weak anti-ulcer activity is mediated through anti-acid activity of the test drug. However, F.D.A.R. produced higher anti-acid activity (61.2%).O.A.R., F.D.A.R. and F.D.A.C. had mild to moderate anti-acid, anti-secretory and anti-ulcer activity."} +{"text": "AbstractHippia packardii (Morrison) and Hippia insularis (Grote) are moved to the genus Elasmia M\u00f6schler as comb. n.Elasmia cave Metzler,sp. n. is described from New Mexico and Texas, and Elasmia mandela santaana Metzler & Knudson,ssp. n. is described from Texas and Oklahoma. A key to the species of Elasmia of southwestern U.S. is provided. Adult male and female moths of Elasmia from southwestern U.S. and their genitalia are illustrated. Hippia M\u00f6schler, 1878 for North America north of Mexico: Hippia packardii , described from Texas; and Hippia insularis , described from Cuba. They listed no species of Elasmia M\u00f6schler, 1886 . Our investigations show that Hippia packardii and Hippia insularis belong in the genus Elasmia, and that Hippia insularis, reported from Texas from the United States. Elasmia mandela santaana is described here from Texas and Oklahoma.om Texas , is an eAdult moths were collected in U.S.D.A. type black-light traps and at black light and sheet as described in Genitalia were examined following procedures outlined in Elasmia is held firmly in place by membranes within the genital capsule, and the aedeagus is nearly always broken into two pieces during the process of removal. The anterior portion is short and abruptly flared out. The posterior portion with the everted vesica is illustrated in this paper Washington, DCUSNMElasmia (not identified to species)feed on Ungnadia speciosa Endl. (Mexican buckeye) and Sapindus saponaria var. drummondii (Hook. & Arn.) L. Benson (soapberry tree) (both Sapindaceae) .In south central Texas, larvae of the genus M\u00f6schler, 1878Hippia mumetes comb. n.Elasmia insularis were illustrated in Elasmia insularis from Cuba. Elasmia insularis is not known to occur in Florida comb. n.http://species-id.net/wiki/Elasmia_packardiiPageBreak pocket appressed to corpus bursae dorsally. Deciduous cornuti from male vesica may be found in corpus bursae.Overall color light gray blue to gray with obscure transverse forewing markings, sometimes showing slight brownish shadings over reniform spot and in postmedial and subterminal areas. Males and females similar in appearance; male antenna narrowly bipectinate in basal \u00be, with dense setae on ventral surface. Female antenna filiform for entire length, with sparse setae. Apex of forewing marked with a diagonal white and dark shade. Forewing length in males 12\u201315 mm , and in females 13\u201316 mm . Male genitalia distinguElasmia packardii from Waco, Bosque County, Texas and Sapindus saponaria var. drummondii (Hook. & Arn.) L. Benson (soapberry tree) (both Sapindaceae) .d Kansas ; it is cMetzlersp. n.urn:lsid:zoobank.org:act:93E887C7-757F-4EC6-B5B5-5E4012D9822Ahttp://species-id.net/wiki/Elasmia_caveElasmia cave Metzler\u201d [red handwritten label] (USNM). Paratypes: 19 males; 14 females: NEW MEXICO: USA: NM: Eddy Co. Carlsbad Caverns NP, arroyo habitat 32\u00b005.98'N 104\u00b033.57'W, 5 September 2010, Eric H. Metzler, CCNP2 uv trp Accssn #: CAVE - 02263. TEXAS: Alpine, Tex., 1\u20137 May 1926, 8\u201314 May 1926, 1\u20137 July 1926, 8\u201314 July 1926, 15\u201321 July 1926, 1\u20137 Aug. 1926, 15\u201321 Aug. 1926, O.C. Poling, Coll[ector]. Barnes Collection (USNM), Texas, Uvalde Co. Concan, 12-V-90, leg. E.C. Knudson. 14-X-93, Concan, Uvalde Co., TX, Coll C. Bordelon. TX: Brewster Co., Big Bend N.P., Green Gulch/5400' 5\u20137-V-97/ECK. Big Bend, Tex. Brewster Co., 6\u20137000 ft., Poling, F. Johnson donor, 8-1-26. USA: Texas: Jeff Davis Co. Davis Mountains, Limpia Canyon, elev: 4920', 30\u00b030.0'N 103\u00b052.5'W, 8 August 1991, Eric H. Metzler. TEXAS: Jeff Davis Co., 25-VI-81, Davis Mt. St. Pk., Jeff Davis Co. TX: Ft. Davis, 3-x-94, leg. E. Knudson. 24 Aug 1995. Jeff Davis Co. Texas, 5-V-78, Kokernaut Creek, leg. E.C. Knudson.PageBreakPageBreak Jeff Davis Co., TX, Ft. Davis, 10,11-IX-10 Bordelon & Knudson coll. Jeff Davis Co., TX, Ft. Davis, 24\u201326-V-07 Bordelon & Knudson coll. TX: Culberson Co., Guadalupe Mts. N.P., Lamar Cyn., Coll. C. Bordelon. TEXAS: Culberson Co., Guadalupe Mts. N.P., Pine Spring, 6\u20138-IX-91, leg. E.C. Knudson. Green Gulch 5400' Big Bend Natl. Park Brewster Co., Texas 4 May 1972 J. G. Franclemont \u2642 Genitalia slide 6419 J. G. Franclemont. Alpine, Brewster Co. Texas 15\u201321 Aug. 1926 O.C. Poling \u2642 Genitalia slide 2535 J. G. Franclemont. .Holotype male: \u201cUSA: NM: Eddy Co. Carlsbad Caverns N[ational] P[ark], riparian habitat, 32\u00b006.566' N 104\u00b028.257' W, 29 August 2006, Eric H. Metzler, CCNP4, uv trp Accsn #: CAVE - 02263\", \u201cHOLOTYPE USNM cave, treated as a noun in apposition, refers to the type locality, Carlsbad Caverns National Park.CAVE is the acronym, used by the U.S. National Park Service, for Carlsbad Caverns National Park. The specific name of this species, Elasmia cave is a dark brown-gray moth with obscure transverse markings. Elasmia cave looks like brown example of Elasmia mandela; Elasmia mandela is dark PageBreakgray brown. The brown color of the imago and its genitalia will separate Elasmia cave from Elasmia packardii, whichis gray blue to gray. The uncus of Elasmia packardii stellate (like a starfish) spicule-shaped cornuti; basal diverticula lightly sclerotized, with two finger-like subbasal diverticulae.Adult male : Head: senitalia : Uncus benitalia , valve senitalia straightGenitalia http://species-id.net/wiki/Elasmia_mandelaOverall color dark gray brown with obscure transverse forewing markings. Males and females similar in appearance. Male antenna narrowly bipectinate in basal \u00be, with dense setae on ventral surface. Female antenna filiform for entire length, with sparse setae. Apex of forewing with a diagonal white mark. Reniform spot outlined with pale-orange scales, not contrasting. Forewing length in males 17.0\u201318.0 mm , and in females 18.0\u201320.0 mm . Male genitalia distinguished by uncus with abruptly widening sides, like a manta ray, and robust saccular area (Barth\u2019s Organ). Female genitalia with membranous papilla anales that are partially hidden from view. Ductus bursae broad and short, dorso-ventrally compressed; corpus bursae round in profile, with a single shark tooth shaped signum, also with a heavily-sclerotized, perpendicular, thumb-like projection ventrally and a sclerotized finger-like pocket appressed to corpus bursae dorsally.Elasmia mandela from Presidio, Mexico, based on a single female specimen. We examined a photograph of the type and it\u2019s genitalia. We also examined specimens from Vera Cruz and Yucatan, Mexico (AMNH), and from Costa Rica (JBS).Elasmia mandela occurs in Mexico and Costa Rica. Its distribution in other Central American countries is unknown. The larval hosts in Costa Rica are one species of Rhamnaceae and 22 species of Sapindaceae (indaceae .Metzler & Knudsonsubsp. n.urn:lsid:zoobank.org:act:9B30138B-9B92-4B81-9797-82B59ABE417Fhttp://species-id.net/wiki/Elasmia_mandela_santaanaElasmia mandela santaana Metzler & Knudson\u201d [red handwritten label] (USNM). Paratypes: 13 males; 10 females: TEXAS: Harris Co: TX. Houston, Leg. E.C. Knudson, 9-VIII-75. Hidalgo Co. TX. Santa Ana NWR, 6-IX-92, leg. E.C. Knudson. Texas: Uvalde Co. Concan, 15-V-10, B/K. Tarrant Co. Texas Benbrook, 30-IV-78, leg. E.C. Knudson. Terrel Co. Tex. Sanderson, 25-IV-81, leg. E.C. Knudson. Kerrville. Texas, Barnes Collection. Kerrville, Texas. VIII 1904. Kerrville, TX. H. Lacy Collector. Kerrville, 4-23-08, TX. F.C. Pratt Collector. Texas, San Patricio Co. Welder Wildlife Refuge near Sinton, Texas, 14-16-VI-85, leg. E.C. Knudson. Hidalgo Co., TX, Bentsen State Park, 6-VIII-94, E. Knudson coll. Montgomery Co. Tex. Sawdust Rd. & I.S. 45, leg. E.C. Knudson, 20-VI-75. Brownsville, Tex III-10-29, F.H. Benjamin collr, Barnes Collection. Alpine, TX. 8\u201314 May, 8\u201314 July, 15\u201321 Aug. 1926, O.C. Poling, Coll[ector]. TEXAS: Smith Cany., Guadalupe Mountains, Culberson Co., 5750\u2019 May 22, 1973, Douglas C. Ferguson. OK: Caddo Co. Methodist Youth Camp 1 October 1994 J.M. Nelson Coll. OK: Tulsa Co. Sand Springs 145th & W. 19th St. Aug 27 - Sept 1, 2008 J.F. Fisher, Collr. at black light. OK: Tulsa Co. Sand Springs 145th & W. 19th St. September 12, 2008 J.F. Fisher, Collr. at black light. .Holotype male: \u201cHidalgo Co. Texas 31-X-83 Santa Ana Refuge leg. E.C. Knudson\u201d \u201cHOLOTYPE USNM santaana,refers to its type locality, Santa Ana National Wildlife Refuge in Texas. The name is treated as a noun in apposition.The name of this subspecies, Elasmia mandela santaana is gray overall. The adult resembles a large example of Elasmia packardii; Elasmia mandela santaana has a contrasting dark scale patch in the reniform/subreniform area. Elasmia mandela santaana (mean forewing length = 16 mm) is larger than Elasmia packardii (mean forewing length = 14 mm) and Elasmia mandela santaana\u2019s Barth\u2019s Organ is relatively larger. The lateral margin of the uncus in Elasmia packardii has a slight shoulder immediately below the apex, whereas in Elasmia mandela santaana the lateral margin of the uncus is flared outward. Elasmia mandela santaana is a gray moth, and Elasmia cave is aPageBreak brown moth. The male and female genitalia of Elasmia mandela santaana are similar to those of Elasmia cave. The costulae of Elasmia cave are abruptly bent and swollen apically is Unganadia speciosa Endl. (Mexican buckeye) (Sapindaceae). The type locality was selected because the U.S. Fish and Wildlife Service will protect it into perpetuity.PageBreakPageBreakIn the U.S., For all characters, except those we noted in the key and diagnoses, the species are closely similar in appearance.The details of the shape of the costulae, in combination with the color and size of the adults, is important in defining the species. The costulae can be slightly variable within a species, thus all the characters should be consulted in making an identification.Elasmia mandela mandela, Elasmia mandela santaana, Elasmia insularis, Elasmia packardii, and Elasmia cave are nearly identical. The male genitalia of Elasmia packardii are distinct. The differences between the male genitalia of Elasmia mandela, Elasmia insularis, and Elasmia cave are more subtle; the most reliable character we found was the shape of the terminal portion of the costulae (Elasmia insularis and Elasmia mandela are closely similar; the superficial appearance of the adults are different. The costulae of Elasmia mandela santaana and Elasmia cave are similar (see the key and The female genitalia of costulae . The cosLepidoptera of the Park initiated by the Park in 2006. This is the second in a series of papers (The specimens from Carlsbad Caverns National Park were collected by Metzler as part of a 10-year study of the f papers detailin"} +{"text": "D.J.V. is a founder, shareholder, consultant, and member of the scientific advisory board of Alectos Therapeutics.Chemistry & Biology apologizes for this omission."} +{"text": "There was an error in the citation. The correct version is available below.Drosophila Brain by Monoclonal Antibodies of the W\u00fcrzburg Hybridoma Library. PLoS ONE 8(9): e75420.Blanco Redondo B, Bunz M, Halder P, Sadanandappa MK, M\u00fchlbauer B, et al. (2013) Identification and Structural Characterization of Interneurons of the doi:10.1371/journal.pone.0075420"} +{"text": "There was an error in the name of the first author. The correct name is: David G. Westcott.The correct citation is: Westcott DG, Mildenberg Z, Bellaiche M, McGowan SL, Grierson SS, et al. (2013) Evidence for the Circulation of Equine Encephalosis Virus in Israel since 2001. PLoS ONE 8(8): e70532. doi:10.1371/journal.pone.0070532"} +{"text": "Eutetranychus banksi (McGregor); Mononychellus tanajoa (Bondar); Oligonychus anonae Paschoal; O. mangiferus (Rahman and Sapra); Tetranychus bastosi Tuttle, Baker and Sales; T. desertorumT. evansi Baker and Pritchard; T. ludeni Zacher; T. mexicanus (McGregor); T. neocaledonicus Andr\u00e9; and T. urticae Koch. Four new localities in Brazil were reported for Eotetranychus tremae De Leon; O. anonae; Panonychus ulmi (Koch); and T. gloveri Baker and Pritchard.In order to contribute to taxonomic information on Tetranychid mites (Acari: Tetranychidae) in South America, surveys were conducted in Brazil and Uruguay (one Department); 550 samples of 120 plant species were collected. Tetranychid mite infestations were confirmed in 204 samples, and 22 species belonging to seven genera of the Bryobiinae and Tetranychinae subfamilies were identified on 58 different host plants. Thirty-six new plant hosts were found in Brazil, South America, and worldwide for the following species: The Tetranychidae Donnadieu family includes a large number of strictly phytophagous mites; a few species are significant agricultural crop pests worldwide .The number of described tetranychids remained stable for 75 years and then increased when their economic incidence for agriculture became more significant . In 1950Tetranychus gloveriMononychellus tanajoa . A permit was requested and permit number 231/2006 CGFAU/IBAMA was issued.A legal permit to collect zoological material for scientific purposes is required by the www.esri.com).Mites were collected between October 2004 and July 2008. A total of 550 samples were collected from several host plants found in five regions in Brazil that include the states of Acre, Bahia, Cear\u00e1, Esp\u00edrito Santo, Goi\u00e1s, Minas Gerais, Mato Grosso do Sul, Paran\u00e1, Pernambuco, Rio Grande do Norte, Rio Grande do Sul, Roraima, Santa Catarina, S\u00e3o Paulo, Sergipe, and the Federal District (www.zeiss.com) and Olympus SZX 122 (www.olympus.com) stereomicroscopes connected to a Highlight 3000\u20131 transilluminator at 50\u00d7 magnification. Finally, Tetranychidae mites were directly mounted on microscopic slide preparations in Hoyer's medium. From each population, 25 females were mounted in dorso-ventral position and ten isolated males were mounted in lateral position to identify the species by morphological analysis. When only a few males were present in a sample, all of them were slide-mounted.Mites were collected from the plants using a washing/sieving extraction method . The reswww.leica-microsystems.com) and interference microscopes in 40\u00d7 and 100\u00d7 objectives and. Morphological identification was conducted by examining relevant taxonomic characteristics of male and female Tetranychidae systematics. The shape of the aedeagus, or male genitalia, was used to classify the species of the 550 plant material samples that were collected (Appendix 1). Twenty-one species of Tetranychinae and one of Bryobiinae were identified on the 204 samples from different localities and inspected hosts .T. urticae and Eutetranychus banksi; T. urticae and M. planki; T. urticae, T. ludeni, and T. desertorum; T. desertorum and M. planki; T. ludeni and M. planki), soybean , cotton , okra , and eggplant (T. urticae and M. tanajoa). T. mexicanus, P. ulmi, Oligonychus aff. mangiferus, and O. fileno were found on grapes in the municipality of Pirapora. Foott , Universidade Federal Rural de Pernambuco, UFRPE, Recife, Pernambuco, 11.VIII.2006.Mucuna aterrima Holland (black mucuna), Institute Agron\u00f4mico de Campinas, ICA, Campinas, S\u00e3o Paulo, 10.I.2006.Phaseolus lunatus L. (lima beans), Embrapa Hortali\u00e7as, Gama, Distrito Federal, 07.XII.2005.E. banksi on Acacia sp. was previously reported in Colombia , Faculdade da Terra, Recanto das Emas, Federal District, 28.XI.2005.Passiflora edulis Sims (sour passion fruit), Lagoa Grande, Minas Gerais, 07.IV.2006.Solanum gilo Raddi (scarlet eggplant), Pipiripau, Planaltina, Distrito Federal, 22.XI.2005 and Caturra farm, Vale do Ribeira, Miracatu, S\u00e3o Paulo, 16.I.2006. Caturra farm, Miracatu, Vale do Ribeira, S\u00e3o Paulo, 16.I.2006.Solanum melongena L. (eggplant), Faculdade da Terra, Recanto das Emas, Federal District, 28.XI.2005.Michelia champaca, P. edulis, S. gilo and S. melongena are new hosts for E. banksi in the world.Tetranychinae Berlese, Tetranychini ReckTetranychus tanajoaManihot ultilissima and M. aipim. Type-locality: Bahia, Brazil.Phaseolus vulgaris L. (beans), Vargem Bonita, N\u00facleo Bandeirantes, Distrito Federal, 23.XI.2005.M. tanajoa infesting beans (P. vulgaris) under field conditions. This mite mainly infests species from the Manihot genus (Euphorbiaceae) and is also reported on plants from the Asteraceae, Caesalpiniaceae, Curcubitaceae, Passifloraceae, Malvaceae, Rubiaceae, and Solanaceae families in the northeastern region of Brazil (Gliricidia sepium (Jacq.) Kunth))] (This is the first report of f Brazil . Plants i Benth) , in Centa Kunth) , and MexKunth))] .Passiflora edulis Sims (yellow passion fruit), Faculdades Integradas da Uni\u00e3o Pioneira de Integra\u00e7\u00e3o Social, UPIS, Planaltina, Distrito Federal, 06.XII.2005.Passiflora edulis is a new host for M. tanajoa. This mite was previously reported on P. cincinnata Mart. by Moraes et al. (P. edulis) and the bean plants (P. vulgaris) were near a cassava plantation (Manihot esculenta Crantz) that was highly infested with M. tanajoa. According to Moraes et al. , in the Ja\u00edba, Mucambinho Project, Minas Gerais, 08.IV.2006.A. muricata) (Annonaceae) and was collected from Lauraceae plants and Vitaceae (Vitis vinifera L.) in Brazil (Annona squamosa (sweetsop) is a new host for the O. anonae.This species was reported in S\u00e3o Paulo on soursop , BR 040, km 40, Luzi\u00e2nia, Goi\u00e1s, 19.XII.2005.Punica granatum L. (pomegranate), Recanto Novo, Minas Gerais, 13.V.2006.Mussaenda sp. (pink mussaenda), Recanto Novo, Minas Gerais 13.V.2006.O. mangiferus on castor oil plants and pomegranates in the Neotropics. This mite was previously found on these host plants in India (Mussaenda L. is reported for the first time as a host for O. mangiferus.This is the first report of in India . MussaenTetranychus (Tetranychus) bastosiMorus rubra L. Type-locality: Crato, Brazil.Gossypium barbadense L. (wild cotton), Empresa de Pesquisa Agropecu\u00e1ria de Minas Gerais \u2014 EPAMIG, Nova Porteirinha, Minas Gerais, 10.IV.2006.T. bastosi on cotton (G. barbadense). This species was observed previously on Malva rotundifolia L. , Institute Agron\u00f4mico de Campinas, ICA, Campinas, S\u00e3o Paulo, 10.1.2006.T. desertorum on M. pruriens in Central America. Therefore, M. aterrima is a new registered host in the Fabaceae family for the T. desertorum in South America.Baker and Pritchard reportedMichelia champaca L. (yellow magnolia), Faculdade da Terra de Brasilia, Recanto das Emas, Distrito Federal, 28.XI.2005 and the Universidade Federal de Lavras, Lavras, Minas Gerais, 06.V.2006.Michelia champaca is a new host for T. desertorum.Solanum melongena L. (eggplant), Faculdade da Terra, Recanto das Emas, Distrito Federal, 28.XI.2005.Solanum gilo Raddi (scarlet eggplant), Pipiripau, Planaltina, Distrito Federal, 22.XI.2005 and Caturra farm, Vale do Ribeira, Miracatu, S\u00e3o Paulo, 16.1.2006. Caturra farm, Miracatu, Vale do Ribeira, S\u00e3o Paulo, 16.I.2006.T. desertorum on eggplant (S. Melongena) in South America previously registered in Japan by Ehara .Carica papaya L. (papaya), Mumbecas farm, Recife, Pernambuco, 11.VIII.2006.Tetranychus evansi was originally described using samples collected from tomato plants , , France.Citrullus lanatus (Thunb.) Matsum and Nakai (watermelon), Embrapa Roraima, Boa Vista, Roraima, 29.III.2005, 12.III.2005 e 30.III.2005.Pelargonium hortorum L. H. Bailey (geranium), Patos de Minas, Minas Gerais, 19.XII.2005.Prunus domestica L. (plumb), Universidade Federal de Lavras, Lavras, Minas Gerais, 09.V.2006.Tetranychus ludeni was previously found on C.lanatus, P. hortorum and P. domestica in Africa, Central America, , Australia, and India (nd India . This isCitrus limonia L. (mandarin-lime), Universidade Federal de Lavras, Lavras, Minas Gerais, 09.V.2006.Citrus limonia as a host for T. ludeni.This is the first report of Tetranychus mexicanus , Tr\u00eas Marias, Minas Gerais, 09.IV.2006.T. mexicanus infesting the E. indica ornamental plant in South America. According to Migeon and Dorkeld , Pirapora, Minas Gerais, 12.IV.2006.T. mexicanus on plants of the Vitaceae family.This is the first report of Eotetranychus neocaledonicusGossypium sp. Type-locality: New Caledonia (Southwest Pacific Ocean).Ocimum basilicum L. (basil), Embrapa Recursos Gen\u00e9ticos e Biotecnologia Cenargen, Bras\u00edlia, Distrito Federal, 23.VII.2006.Morus rubra L. (mulberry), SQS 202 Sul, Bras\u00edlia, Distrito Federal, 23.VI.2008Cestrum intermedium Sendtn. (night blooming jasmine), Recanto Novo, Minas Gerais, 13.V.2006Cestrum intermedium, O. basilicum, and M. rubra are new hosts for T. neocaledonicus in the world. However, the presence of T. neocaledonicus on Cestrum sp. has been registered in the state of Rio de Janeiro were registered as hosts for T. neocaledonicus in Cuba, India, Japan, and Thailand , Itaqui, Rio Grande do Sul, 29.IX.2007.Parthenium sp. (parthenium), Universidade Federal de Santa Maria, Rio Grande do Sul, 26.IX.2007.T. urticae on A. trifida L. in the state of S\u00e3o Paulo. Ambrosia polystachya is a new host for T. urticae in Brazil and in the world.Paschoal first coTetranychus urticae on Parthenium sp. were made in India (Parthenium sp. occurred in Rio Grande do Sul.Reports of in India . In the Pyrostegia venusta Miers (flame vine), Universidade Federal de Lavras, Lavras, Minas Gerais, 09.V.2006.T. urticae infestations on P. ignea C. Presl. in Costa Rica. This was the first report of T. urticae infesting P. venusta in the world.Vargas et al. describePhaseolus lunatus L. (lima beans), Embrapa Hortali\u00e7as, Gama, Distrito Federal, 07.XII.2005.Macroptilium atropurpureum (L.) (siratro), Caliman farm, Cruz das Almas, Bahia.T. urticae on P. lunatus were reported in the United States, India, and Thailand (M. atropurpureum in Greece (Phaseolus lunatus and M. atropurpureum are new hosts for T. urticae in South America.Infestations of Thailand and on Mn Greece . PhaseolPassiflora edulis Sims (yellow passion fruit), Embrapa Roraima, Boa Vista, Roraima, 17.V.2007.Tetranychus urticae on passion fruit (P. caerulea L. and P. edulis) was reported in Venezuela (Passiflora sp.) (T. urticae on passion fruit (P. edulis) in Brazil.enezuela and Austora sp.) . This isTriticum aestivum L. (wheat), Embrapa Trigo, Passo Fundo, Rio Grande do Sul, 27.IX.2006.T. urticae infestation of wheat crops (Triticum sp.) was registered in Greece , Faculdade da Terra de Bras\u00edlia, Recanto das Emas, Distrito Federal, 28.XI.2005.Tetranychus urticae on Zingiberaceae (Curcuma longa L.) were reported in India in the world.Cases of in India . This isT. urticae).The single sample collected in Uruguay revealed a new host for the two-spotted spider mite (Lantana camara L. (wild sage), Rio Negro, San Javier, Uruguay, 06.VI.2007. .Tetranychus urticae infesting L. camara was first observed in the United States and in India in the state of S\u00e3o Paulo. Its presence on A. squamosa in the municipality of Mocambinho, in northern Minas Gerais, indicates a new locality for this species in Brazil.Paschoal , 1970b dTetranychus gloveriGossypium hirsutum L. Type-locality: Baton Rouge, United StatesTetranychus gloveri was reported on beans in Bahia (Carica. papaya L.) in the state of Rio Grande do Norte indicate a new locality for this species.in Bahia and on pin Bahia . ReportsTetranychus ulmiUlmus sp. Type-locality: Regensburg, Germany.P. ulmi) on grape vines (Vitis vinifera L.) were registered for the first time in Brazil in 2008 when damages caused by these mites were first noticed on crops in Rio Grande do Sul growing in orchards in the south of the country. However, European countries such as France, Austria, Portugal, Italy, and Greece consider the P. ulmi a grape vine pest to Minas Gerais (2006) state could be the result of the two states trading plant propagation material. The hypothesis that European mites were introduced into Brazil cannot be discarded considering that P. ulmi were discovered approximately 40 years ago and have only recently been causing damage to grape vines. Ferla and Botton was collected from citrus in the municipality of Boa Vista, State of Roraima , M. tanajoa (2), O. anonae (1), O. mangiferus (3), T. bastosi (1), T. desertorum (4), T. evansi (1), T. ludeni (4), T. mexicanus (2), T. neocaledonicus (3), and T. urticae (8), as well as one in Uruguay for T. urticae. New localities were registered in Brazil for E. tremae, O. anonae, T. gloveri and P. ulmi.Thirty-five new hosts were registered for 11 tetranychid species already known in Brazil:"} +{"text": "The molecular history of animal evolution from single-celled ancestors remains a major question in biology, and little is known regarding the evolution of cell cycle regulation during animal emergence. In this study, we conducted a comprehensive evolutionary analysis of CDK and cyclin proteins in metazoans and their unicellular relatives.Dictyostelium discoideum. In contrast, cyclin subfamilies B, A, E, and D, which are cell cycle-related, have distinct evolutionary histories. The cyclin B subfamily is generally conserved in D. discoideum, fungi, and animals, whereas cyclin A and E subfamilies are both present in animals and their unicellular relatives such as choanoflagellate Monosiga brevicollis and filasterean Capsaspora owczarzaki, but are absent in fungi and D. discoideum. Although absent in fungi and D. discoideum, cyclin D subfamily orthologs can be found in the early-emerging, non-opisthokont apusozoan Thecamonas trahens. Within opisthokonta, the cyclin D subfamily is conserved only in eumetazoans, and is absent in fungi, choanoflagellates, and the basal metazoan Amphimedon queenslandica.Our analysis divided the CDK family into eight subfamilies. Seven subfamilies are conserved in metazoans and fungi, with the remaining subfamily, CDK4/6, found only in eumetazoans. With respect to cyclins, cyclin C, H, L, Y subfamilies, and cyclin K and T as a whole subfamily, are generally conserved in animal, fungi, and amoeba Our data indicate that the CDK4/6 subfamily and eumetazoans emerged simultaneously, with the evolutionary conservation of the cyclin D subfamily also tightly linked with eumetazoan appearance. Establishment of the CDK4/6-cyclin D complex may have been the key step in the evolution of cell cycle control during eumetazoan emergence. Cyclin-dependent kinases (CDKs) are serine and threonine kinases whose actions are dependent on the binding of regulatory subunits known as cyclins ,2. Vario2+ signaling \u2018Toolkit\u2019 ) [The evolution of metazoans from protozoans is a major milestone in the history of life. This transition has been generally marked by increases in the number of genes involved in cell differentiation, cell-cell communication, and cell adhesion -12. The olkit\u2019 ) -21, and olkit\u2019 ) -27 durinAmphimedon queenslandica proteins, it has been proposed that the emergence of metazoan multicellularity may have been related to the evolution of various genes functioning in cell cycling and growth, programmed cell death, cell-cell and cell-matrix adhesion, developmental signaling and gene regulation, allorecognition and innate immunity, and cell type specialization [In addition to cell communication and cell adhesion proteins, other proteins may be linked with metazoan emergence. Based on a comprehensive phylogenetic analysis of sponge lization .As implied by the aforementioned study, investigation of the evolutionary history of cell cycle control genes could enhance our understanding of metazoan emergence from single-celled ancestors. At present, however, comprehensive evolutionary analyses have been carried out only for a few cell cycle control genes, such as P53, RB, and E2F families ,30.The core machinery of the animal cell cycle can generally be traced back to early eukaryotes -33. It wAccording to recent reports, 20 CDK and approximately 30 cyclin genes are present in humans ,36,37. TMonosiga brevicollis[Amphimedon queenslandica[Trichoplax adhaerens[Nematostella vectensis[Salpingoeca rosetta and the filasterean Capsaspora owczarzaki, that are recognized as close relatives of metazoans based on data from the Origins of Multicellularity project [Taking advantage of the increasing number of sequenced genomes, in this study we conducted a comprehensive evolutionary analysis of 176 CDK and 226 cyclin genes from 18 representative organisms. Our analysis incorporated several organisms important to the study of metazoan emergence, such as the closest known metazoan relative, the choanoflagellate evicollis; the oldnslandica; the earadhaerens; and thevectensis. We also project . Our reshttp://www.ncbi.nlm.nih.gov/) for 15 organisms: Homo sapiens, Ciona intestinalis , Strongylocentrotus purpuratus (S. purpuratus), Branchiostoma floridae, Drosophila melanogaster (D. melanogaster), N. vectensis, T. adhaerens, A. queenslandica, Monosiga brevicollis, S. rosetta, C. owczarzaki, Schizosaccharomyces pombe (S. pombe), Saccharomyces cerevisiae (S. cerevisiae), Coprinopsis cinerea (C. cinerea), and Dictyostelium discoideum (D. discoideum). The search results were used as new queries in a second round of BLAST searching, which was continued until no new sequences were returned. We also performed a similar BlastP search against the Broad Institute database [http://www.broadinstitute.org/annotation/genome/multicellularity_project/MultiHome.html) to collect CDK sequences from three unicellular organisms: Sphaeroforma arctica (S. arctica), Spizellomyces punctatus (S. punctatus), and Thecamonas trahens (T. trahens), as these sequences are not available in the NCBI database. For CDK genes, only the longest protein sequence encoded by each gene was retained. We also carried out a preliminary phylogenetic analysis on all putative CDK family proteins collected from Blast searching. Proteins clustering with human CDKs were used in subsequent analyses, whereas those clustering with other human protein kinases, such as MAP kinases, were discarded.For CDK proteins, we performed PSI-Blast searches using human CDK1 and CDK7 protein sequences as queries against database against non-redundant proteins from GenBank was also carried out [S. arctica, S. punctatus, and T. trahens), Cyclin-N domain-containing proteins were also collected from the Broad Institute database [http://pfam.sanger.ac.uk/search) and SMART (http://smart.embl-heidelberg.de/) databases [Using human cyclin B, cyclin C, and cyclin Y proteins as queries, similar Blast searches were carried out to identify cyclin proteins from related organisms in the NCBI and Broad Institute databases. Because cyclin proteins are greatly diverged, an HMM search . Tree files were viewed using the Dendroscope program [After evaluating several multiple alignment programs, we used MSAProbs for mult PROMALS , a progr PROMALS . Poorly PROMALS . ML tree PROMALS as imple PROMALS with 100 PROMALS , with Ma program , and phy program .E-values returned for members of a representative CDK or cyclin subfamily were five orders of magnitude better than those of the next best-scoring CDK or cyclin subfamily were considered to be orthologs of that subfamily. Such a \u201cfive-orders criterion\u201d has recently been described and used to identify Arf GAP orthologs [As suggested in a recent review , ortholorthologs . Cyclin As summarized in Table\u00a0H. sapiens, N. vectensis, T. adhaerens, A. queenslandica, M. brevicollis, and S. rosetta7 as one group , CDK9 , CDK10/11 (including CDK10 and CDK11), CDK1 , CDK4/6 (including CDK4 and CDK6), and CDK5 , but is absent in S. cerevisiae, S. pombe, T. trahens, and D. discoideum and N. vectensis (gi:156374066), and is absent in the basal metazoan A. queenslandica, choanoflagellates, and other investigated unicellular organisms are present in basal metazoans sis gi:1574066, anH. sapiens, N. vectensis, T. adhaerens, A. queenslandica, M. brevicollis, and S. rosetta and CDK11 (gi:167538010). In further analysis, we found that one S. punctatus protein (SPPG_05640) was classified into the CDK10 clade, and that one S. pombe protein (Ppk23/gi:19112531) and one C. cinerea protein (gi:299755758) were placed in the CDK11 clade and T. trahens (AMSG_04682) were only grouped into the CDK10/11 subfamily, and were not found in clades CDK10 and CDK11. In addition to their roles in regulating transcription, CDK10 and CDK11 display distinct functions during the G2/M transition [The CDK10/11 subfamily comprises clades CDK10 and CDK11 and T. adhaerens (gi:196003954), and similarly CDK2/3 clade members are present in A. queenslandica (gi:340379293) and T. adhaerens (gi:196013348) , S. rosetta, fungi, T. trahens, and D. discoideum, however, are not placed into CDK1 or CDK2/3 clades , CDK16/17/18 (gi:195996637), and CDK14/15 (gi:196001193) clades is clustered into CDK5, whereas another (gi:167522415) is placed into CDK16/17/18 was identified as an ortholog of cyclin Y and N. vectensis (gi:156350442), but are absent in M. brevicollis, S. rosetta, and A. queenslandica , plant D-type cyclin did not cluster together with animal cyclin D in a previous phylogenetic analysis [T. trahens. The Blast E-value for this protein against human cyclin D is approximately 1\u2009\u00d7\u200910\u221215. This result indicates that the cyclin D subfamily arose in early eukaryotes, and that the absence of cyclin D in fungi and many other unicellular organisms may be due to lineage-specific gene loss in these organisms. Similar to plant organisms, the non-opisthokont T. trahens does not possess an ortholog of the CDK4/6 subfamily. Our alignment of representative cyclin D subfamily proteins from H. sapiens, N. vectensis, T. adhaerens, and T. trahens is displayed in Figure\u00a0We found that orthologs of cyclin D are present in is gi:15650442, buanalysis . Our phyC. owczarzaki, S. arctica, A. queenslandica, and N. vectensis , but have generally been lost in fungi and most other unicellular opisthokonts, such as M. brevicollis, S. rosetta, C. owczarzaki, and S. arctica. Our analysis also found that cyclin E is not restricted to animals, but is present in several unicellular organisms.Our analysis has provided detailed evolutionary information on CDK and cyclin subfamilies in metazoans and related organisms. Our data are the first to reveal that cyclin D orthologs are present in a non-opisthokont and yeasts (S. cerevisiae and S. pombe). In animals, CDK4/6 and cyclin D have been determined to function in the G1 phase, human CDK2 and cyclin A/E in S and G2 phases, and CDK1 and cyclin B in the M phase [S. cerevisiae CDK1 (Sce-CDC28/gi:6319636) functions in G1, S, G2, and M phases with different cyclins [M. brevicollis[, A. queenslandica[, and T. adhaerens[, which occupy key positions for metazoans origination from their single-celled ancestors organisms may function throughout the cell cycle with different cyclins, similar to S. cerevisiae CDK1 (Sce-cdc28/gi:6319636) are conserved in metazoans and fungi, with CDK4/6 subfamily found only in eumetazoans. As to cyclins, cyclin C, H, L, Y subfamilies, and cyclin K and T as a whole subfamily, are conserved in animal, fungi, and amoeba Our data indicate that the CDK4/6 subfamily and eumetazoans emerged simultaneously, with the evolutionary conservation of the cyclin D subfamily also tightly linked with eumetazoan appearance. We speculated that establishment of the CDK4/6-cyclin D complex may have been the key step in the evolution of cell cycle control during eumetazoan emergence.H. sapiens: Homo sapiens; C. intestinalis: Ciona intestinalis; S. purpuratus: Strongylocentrotus purpuratus; B. floridae: Branchiostoma floridae; D. melanogaster: Drosophila melanogaster; N. vectensis: Nematostella vectensis; T. adhaerens: Trichoplax adhaerens; A. queenslandica: Amphimedon queenslandica; M. brevicollis: Monosiga brevicollis; S. rosetta: Salpingoeca rosetta; C. owczarzaki: Capsaspora owczarzaki; S. arctica: Sphaeroforma arctica; S. pombe: Schizosaccharomyces pombe; S. cerevisiae: Saccharomyces cerevisiae; C. cinerea: Coprinopsis cinerea; S. punctatus: Spizellomyces punctatus; T. trahens: Thecamonas trahens; D. discoideum: Dictyostelium discoideum.The authors declare that they have no competing interests.LC and LY conceived the study. LC, FC, JC, and JX collected the data. LC and FC performed the phylogenetic analyses, and JX conducted the reciprocal blast analysis. LC and XY wrote the manuscript. All authors read and approved the final manuscript.T. trahens and D. discoideum was carried out using PROMALS program [All Multiple alignments of CDK or cyclin proteins which were used for phylogenetic analysis. Multiple alignments of full-length proteins were mainly carried out using MSAProbs program , however program , Then thClick here for fileCDK sequences from 18 organisms.Click here for fileCyclin sequences from 18 organisms.Click here for fileT. adhaerens, C. intestinalis, B. floridae, S. purpuratus and D. melanogaster. Maximum likelihood analysis was conducted using RAxML program, and Bayesian analysis was carried out using PHYLOBAYES 3.3. Both methods produced trees with nearly identical topologies. The first numbers above branches indicate Bayesian posterior probabilities (only these key branches are labeled), and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-GSK3alpha, Hsa-MAK, and Hsa-HCDKL1 were used as outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Cin: C. intestinalis; Bfl: B. floridae; Spu: S. purpuratus; Dme: D. melanogaster.Phylogenetic analysis of CDK family proteins in H. sapiens, Click here for fileT. adhaerens, C.owczarzaki , S. arctica, S.cerevisiae, S.pombe, C. cinerea, S. punctatus, T. trahens and D. discoideum. Maximum likelihood analysis was conducted using RAxML program, and Bayesian analysis was carried out using PHYLOBAYES 3.3. Both methods produced trees with nearly identical topologies. The first numbers above branches indicate Bayesian posterior probabilities (only these key branches are labeled), and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-GSK3alpha, Hsa-MAK, and Hsa-HCDKL1 were used as outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Cow: C.owczarzaki; Sar: S. arctica; Sce:S.cerevisiae; Spo:S.pombe; Cci:C. cinerea; Spu:S. punctatus; Ttr:T. trahens; Ddi:D. discoideum.Phylogenetic analysis of CDK family proteins in H. sapiens, Click here for fileEvolutionary relationship of CDK family proteins from 18 representative organisms. Summary of the evolutionary relationship of CDK family proteins based on the results of phylogenetic analyses of CDK family proteins , and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-Cables1 and Hsa-Cables2 were used as the outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Cin: C. intestinalis; Bfl: B. floridae; Spu: S. purpuratus; Dme: D. melanogaster.Phylogenetic analysis of cyclin family proteins in H. sapiens, T. Click here for fileT. adhaerens, C.owczarzaki , and S. arctica. Maximum likelihood analysis was conducted using RAxML program, and Bayesian analyses were carried out using PHYLOBAYES 3.3. Both methods produced trees with nearly identical topologies. The first numbers above branches indicate Bayesian posterior probabilities (only these key branches are labeled), and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-Cables1 and Hsa-Cables2 were used as the outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Cow: C.owczarzaki; Sar: S. arctica.Phylogenetic analysis of cyclin family proteins in H. sapiens, Click here for fileT. adhaerens, S.cerevisiae, S.pombe, C. cinerea, and punctatus. Maximum likelihood analysis was conducted using RAxML program, and Bayesian analyses were carried out using PHYLOBAYES 3.3. Both methods produced trees with nearly identical topologies. The first numbers above branches indicate Bayesian posterior probabilities (only these key branches are labeled), and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-Cables1 and Hsa-Cables2 were used as the outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Sce: S.cerevisiae; Spo: S.pombe; Cci: C. cinerea; Spu: S. punctatus.Phylogenetic analysis of cyclin family proteins in H. sapiens, Click here for fileT. adhaerens, T. trahens and D. discoideum. Maximum likelihood analysis was conducted using RAxML program, and Bayesian analyses were carried out using PHYLOBAYES 3.3. Both methods produced trees with nearly identical topologies. The first numbers above branches indicate Bayesian posterior probabilities (only these key branches are labeled), and the second numbers above branches indicate ML bootstrap percentages. The scale bar shows the number of substitutions per site. The sequences of Hsa-Cables1 and Hsa-Cables2 were used as the outgroup. All proteins are labeled with their accession numbers and their specie name as prefix. Abbreviations: Hsa: H. sapiens; Tad: T. adhaerens; Ttr:T. trahens; Ddi:D. discoideum.Phylogenetic analysis of cyclin family proteins in H. sapiens, Click here for fileEvolutionary relationship of cyclin family proteins from 18 representative organisms. Summary of the evolutionary relationship of cyclin family proteins based on the results of phylogenetic analyses of cyclin family proteins(Figure\u00a0Click here for fileH. sapiens, N. vectensis, T. adhaerens, A. queenslandica, M. brevicollis, and S. rosetta. Neighbor-Net analysis was conducted using SplitsTree v.4 program [H. sapiens; Nve, N. vectensis; Tad, T. adhaerens; Aqe, A. queenslandica; MBr, M. brevicollis. The alignment used for this analysis is found in Additional file phylogenetic network analysis for Cyclin B like group proteins from program with 100Click here for file"} +{"text": "Equal contribution was unassigned. Margaret C. W. Ho and Benjamin J. Schiller contributed equally to this work."} +{"text": "AbstractStenolophus thoracicus Casey is revalidated. The species is redescribed based on a study of the syntypes and of several conspecific specimens from eastern North America. The species differs from the other eastern species of the subgenus Agonoleptus in having the metasternum shorter and the wings reduced to tiny stubs. The dorsal habitus and median lobe of the aedeagus, along with the structures of the internal sac, are illustrated. Stenolophus thoracicus Casey with Stenolophus conjunctus (Say) pointing out, however, that the microsculpture on the pronotum of the female \u201ctype\u201d was considerably stronger than normal. A study of Casey\u2019s syntypes revealed that the specimens are in fact specifically distinct from those of Stenolophus conjunctus. The purpose of this paper is to redescribe Stenolophus thoracicus and to discuss the structural differences between Stenolophus thoracicus and the other eastern species of the subgenus Agonoleptus Casey.Stenolophus thoracicus were observed in material from University of California at Berkely, Milwaukee Public Museum, Mississippi State University, and Washington State University.The holdings of the following collections were studied: Buffalo Museum of Science, New York (BMSC), California Academy of Sciences (CAS), National Collection of Insects, Arachnids and Nematodes (CNC), Field Museum of Natural History, Chicago (FMNH), Los Angeles County Museum of Natural History (LACM), Museum of Comparative Zoology (MCZ), Michigan State University Collection (MSUC), North Dakota State University (NDSU), National Museum of Natural History (USNM), University of Wisconsin-Madison Insect Research Collection (WIRC), and the collection of Peter W. Messer (PWM). No examples of Casey, 1914Stenolophus thoracicus Stenolophus thoracicus , each labelled later as \u201cparatype.\u201d The unit tray bears a label \u201ctype missing Lindroth 73.\u201d It seems that the Casey\u2019s collection included another female specimen, labelled as \u201ctype,\u201d that Lindroth studied before 1968.Lectotype (\u2642), designated by Coloration. Clypeus and labrum reddish; frons reddish-brown to reddish-black; antennomeres 1 and 2 yellow, antennomeres 3\u201311 slightly darker, brownish-yellow; pronotum entirely yellow to reddish-yellow; elytra reddish-brown to reddish-black, with base, intervals 1 and lateral margins paler, more or less yellowish to reddish; elytral epipleura yellow; legs entirely yellow. Microsculpture. Frons with isodiametric meshes, meshes indistinct or almost so in the male, faint but distinct in the female; pronotum with linear microlines, microlines indistinct or almost so in the male, distinct in the female; elytra with markedly transverse meshes, meshes well impressed in both sexes. Head. Clypeo-ocular line evident, complete . Pronotum. Proportionally wide, LP/WP = 0.73\u20130.79 ; maximum width clearly anterior to middle; anterior angle markedly protruding; basal impression shallow, almost indistinct in some specimens; basal bead reaching just beyond level of basal impression. Elytra. Striae impressed, shallow but deeper toward apex, impunctate; intervals flat. Thorax . Metasternum, short, length behind mesocoxa about 0.7 that of metacoxa along same line. Male genitalia. Median lobe with apex hooked; internal sac with two large U-shaped sclerotized structures and a small \u201cscaly body\u201d near middle.Apparent body length: 3.5\u20134.1 mm.PageBreakIowa City, Johnson Co., 1.X.1917, L. Buchanan . Okoboji, Dickinson Co., VIII . Kansas. Atchison, Atchison Co., 25.IV. . Kentucky. Frankfort, Franklin Co., 16.IV.1892 . Maryland. Baltimore, 16.V.1909, F.E. Blaisdell . Massachusetts. Cambridge, Middlesex Co., 18.III.1974 . Waverly, Middlesex Co. . Springfield, Hampden Co., G. Dimmock . Dover, Norfolk Co., 19.IV.1904, F.C. Bowditch . Dover, Norfolk Co., 4.VI.1908, A. P. Morse . Wachusett, Worcester Co., 19.IV.1906, Perry Gardner Bolster . Bolton, Worcester Co., 13.IV.2010, T. Murray . Michigan. Rose Lake Wildlife Experiment Station, Clinton Co., 18.XII.1971, D.K. Young . Detroit, Wayne Co. . Missouri. \u201cMo\u201d . Kansas City, 26.IV.1898 . New Jersey. \u201cN.J.,\u201d R. Hopping . Tenafly, Bergen Co., 17.III.1917, F.M. Schott . New York. \u201cN.Y.\u201d Schaupp . Ithaca, Tompkins Co., 25.VIII.1911, Van Dyke . North Dakota. Mirror Pool, Richland Co., T135N-R52W-Sec 8, NE \u00bc, 27.V.1966, Gordon & Aarhus . Ohio. Wayne Co., 1.V.1938 . W\u2019 Loo Twn., Athens Co., 6.V.1936, W. Stehr . Canaan Twn., Athens Co., 24.III.1939, W.C. Stehr . Carbondale, Athens Co., 21.V.1938, 8.IV.1948, W.C. Stehr . Columbus, Franklin Co., 23.IV.1929, R.T. Everly . Pennsylvania. 6 km SW Buck Valley at Sideling Hill Creek, 39\u00b044'N, 78\u00b021'W, 10.X.1992, W.E. Steiner & J.M. Swearingen [shale barren slope]. Frankford, Philadelphia Co., A. Schmidt . South Dakota. [East] Sioux Falls, Minnehaha Co., 25.IV.1967, V.M. Kirk . Tennessee. Nashville, Davidson Co. . Vermont. Topsham, Orange Co., 27.X.2008, T. Murray . Virginia. \u201cVa\u201d, 29.V.1881 . Great Falls, Fairfax Co., 29.X., Banks . Vienna, Fairfax Co., 2.X.1932 . Fairfax Co., 21.IX.1930, A. Nicolay . Fairfax Co., 4.VI.1972, R. Gordon & A. Cushman . 9 km N Mountain Lake, Wind Rocks, Giles Co., 19.VIII.1984, W. Steiner & J. Hill . Wisconsin. \u201cWis\u201d E. Chope . Mud Lake Nat. Site, Columbia Co., 21\u201327.V.1996 . Madison, Dane Co., 27.IV.1910, J.G. Sanders . Nevin Marsh, Dane Co., 12.VI.1974, D.T. Bach . Green Lake Co., 22.IV.2000, C. Buss . Hemlock Draw, Sauk Co., 6.V.2007, J.P. Gruber . Springfield Nat. Site, Walworth Co., 8\u201315.VII.1996 .This species ranges from east-central Vermont to southeastern North Dakota, southwardly to northeastern Kansas, Tennessee, and northeastern Virginia . We haveNo information is available about the habitat requirements of the species.Nine specimens were dissected and their wings were reduced to tiny stubs. Considering the size of the metasternum, the species is very likely constantly brachypterous.Stenolophus thoracicus belongs to the subgenus Agonoleptus Casey which includes six other species-group taxa: Stenolophus conjunctus (Say), Stenolophus rotundicollis , Stenolophus rotundatus LeConte, Stenolophus parviceps (Casey), Stenolophus unicolor Dejean, and Stenolophus unicolor dolosus Casey. The last three-named taxa are found in southwestern United States and are not further dealt with. The other taxa occur sympatrically with Stenolophus thoracicus east of the Rocky Mountains, although one of them, Stenolophus conjunctus, also extends to the West Coast.PageBreakStenolophus thoracicus differ most notably from those of the three other eastern species of the subgenus in having the metasternum shorter and the wings highly reduced. For comparative purpose, the ratio of the metasternal length behind the mesocoxa and the metacoxal length measured along the same line varies between 1.0 and 1.2 in Stenolophus conjunctus, Stenolophus rotundicollis, and Stenolophus rotundatus. In addition, the pronotum is more narrowed posteriorly on average.Adults of Stenolophus conjunctus differ from those of Stenolophus thoracicus also in having the microsculpture on pronotum indistinct in both sexes and the elytral microsculpture less impressed. The apex of the median lobe of the aedeagus is proportionally longer, not hooked, and the internal sac has two slightly curved sclerotized structures and the microsculpture on pronotum and elytra more deeply impressed. The apex of the median lobe is hooked but the internal sac contains two small U-shaped and one slender, straight sclerotized structures , and more convex, the clypeo-ocular line clearly more deeply impressed, the anterior angles of the pronotum less protruding, the medial elytral striae deeper, and the pronotum and elytra without microsculpture. The apex of the median lobe is hooked, more bluntly so than in Stenolophus thoracicus and Stenolophus rotundicollis, and the internal sac has one large U-shaped and one straight sclerotized structures (see Adults of ures see ."} +{"text": "As a result of errors in the typesetting process, the citation was incorrect. The correct version of the citation is available below.Drosophila melanogaster Acetylcholinesterase for Detection of Organic Phosphorus and Carbamate Pesticides. PLoS ONE 8(9): e72986. doi:10.1371/journal.pone.0072986 Li J, Ba Q, Yin J, Wu S, Zhuan F, et al. (2013) Surface Display of Recombinant"} +{"text": "The affiliation for David R. Spring was listed incorrectly, but appears correctly, above. Panel B in"} +{"text": "There are several errors in the author information.The Corresponding Author should be Martina Hedenius. The email address, martina.hedenius@neuro.uu.se, is correct.The third author's name is spelled incorrectly. The correct name is Per A. Alm.Three authors, Michael T. Ullman, Margareta Jennische and Jonas Persson, should be noted as joint senior authors of this work."} +{"text": "Bacterium tularense after Tulare County, California, location of their study. In 1928, Edward Francis, a US Public Health Service bacteriologist, linked B. tularense with deer fly fever\u2015tularemia transmitted by deer flies from infected wild rabbits to humans. In 1974, B. tularense was renamed Francisella tularensis in recognition of Dr. Francis\u2019 many contributions to our knowledge of tularemia.While studying plague in ground squirrels in 1911, George McCoy and Charles Chapin discovered a bacterium that caused a different disease. They named the pathogen http://history.nih.gov/research/downloads/Notable_Cont_Med_Research.pdf; Francis E. Sources of infection and seasonal incidence of tularemia in man. Public Health Rep. 1937;52:103\u201313; McCoy GW, Chapin CW. Further observations on a plague-like disease of rodents with a preliminary note on the causative agent, Bacterium tularensis. J Infect Dis. 1912;10:61\u201372; Sj\u00f6stedt A. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. 2007;1105:1\u201329. PubMeddoi:10.1196/annals.1409.009Sources: Barry, J. Notable contributions to medical research by public health scientists. Public Health Service Publication No. 752. 1960 [cited 2011 Feb 25]."} +{"text": "Cyprinus carpio), the grass carp (Ctenopharyngodon idella), and the silver carp as well as from three freshwater fish species which were found in some fish farms of the same province. The parasitic fauna included one mastigophoran, three apicomplexans, 13 ciliophorans, five myxozoans, five trematodes, 45 monogeneans, five cestodes, three nematodes, two acanthocephalans, nine arthropods, and one mollusc. The common carp was found to harbour 81 species of parasites, the grass carp 30 species, the silver carp 28 species, L. abu 13 species, C. auratus one species, and H. fossilis one species. A host-parasite list for each fish species was also provided. Literature reviews of all references concerning the parasitic fauna of fishes in fish farms of Babylon province, middle of Iraq, showed that a total of 92 valid parasite species are so far known from the common carp ( Although fish farming in Iraq started in 1955 with a small pond in Al-Zaafaraniya, south of Baghdad city . HoweverUnder extensive fish culture and inadequate administrative and control measures, fish farms are vulnerable to great hazards due to the infection with parasites and other disease agents , 4, 5. MIn connection with the parasites of cultured fishes of Babylon province, Mhaisen et al. surveyedA total of 50 references dealing with the parasites of farm fishes of Babylon province were used to prepare the present paper. Data from such references was gathered to provide host-parasite and parasite-host lists. The systematic account of these parasites is based on some electronic sites \u201312 as weThe index-catalogue of parasites and disease agents of fishes of Iraq was usedFew fish farms in Babylon province were surveyed for some parasitic infections. Fishes from Al-Furat Fish Farm received the greatest attention in this respect. So far 25 chronologically arranged references \u201342 were L. abu 13 species, C. auratus one species, and H. fossilis one species. The layout and names of the major taxonomic groups (phyla and classes) followed a checklist of an FAO Fisheries Technical Paper [Surveying the literature concerning the parasites so far recorded from fish farms of Babylon province showed the presence of 92 parasite species. These parasites included one mastigophoran, three apicomplexans, 13 ciliophorans, five myxozoans, five trematodes, 45 monogeneans, five cestodes, three nematodes, two acanthocephalans, nine arthropods, and one mollusc. The common carp was found to harbour 81 species of parasites, the grass carp 30 species, the silver carp 28 species,al Paper . These mThe parasite-host list is arranged in the major groups (phyla or classes) of parasitic fauna according to Kirju\u0161ina and Vismanis . For eac Ichthyobodo. The systematic account of this parasite, followed by parasite-host list, is given here.The phylum Mastigophora is represented in farm fishes of Babylon province with only one parasite species of the genus\u2009Class Kinetoplastidea\u2009Order Kinetoplastida\u2009Family Bodonidae\u2009Ichthyobodo necator Pinto, 1928 Phylum MastigophoraIchthyobodo necator Pinto, 1928, was erroneously reported as Costia necatrix from the skin and gills of C. carpio [ C. necatrix in Iraq was from body surface of H. fossilis from Al-Ashar Canal at Basrah [ C. necatrix) in Iraq [. carpio . The firt Basrah . Seven f in Iraq . Eimeria and one unspecified species to the genus Haemogregarina. The phylum Apicomplexa, which is known as phylum Myzozoa according to WoRMS , is repr\u2009Class Sporozoa\u2009Order Eucoccidiorida\u2009Family Eimeriidae\u2009Eimeria dogieli Pellerdy, 1963\u2009Eimeria mylopharyngodoni Chen, 1956\u2009Family Haemogregarinidae\u2009Haemogregarina sp. Phylum Apicomplexa Eimeria dogieli Pellerdy, 1963, was recorded from the intestine of C. carpio [ E. dogieli from fishes of Iraq [. carpio . So far, of Iraq .Eimeria mylopharyngodoni Chen, 1956, was recorded from C. carpio [ mylopharyngodon and no authority, site of infection, parasite description, and illustration were given for this parasite by Hussain et al. [ C. carpio externally while E. mylopharyngodoni is known to infect intestine, kidneys, and liver of fishes [ E. mylopharyngodoni from fishes of Iraq [. carpio . The spen et al. . So thisn et al. examinedf fishes . This is of Iraq .Haemogregarina sp. was found on gills of C. carpio [ Haemogregarina were so far recorded from blood of three fish species in Basrah province only [ Haemogregarina sp. from gills of C. carpio by Hussain et al. [. carpio . In Iraqnce only . So we tn et al. with nei Chilodonella, Ichthyophthirius, and Tripartiella, five to the genus Apiosoma, and four to the genus Trichodina in addition to unspecified species of the genus Trichodina. The phylum Ciliophora is represented in farm fishes of Babylon province with 13 species, three of which belonged to the genera\u2009Class Kinetophragminophorea\u2009Order Cyrtophorida\u2009Family Chilodonellidae\u2009Chilodonella cyprini Strand, 1928\u2009Class Oligohymenophorea\u2009Order Hymenostomatida\u2009Family Ichthyophthiriidae\u2009Ichthyophthirius multifiliis Fouquet, 1876\u2009Order Petrichida\u2009Family Epistylididae\u2009Apiosoma amoebae Lom, 1966\u2009Apiosoma cylindriformis \u2009Apiosoma minuta Lom, 1966\u2009Apiosoma piscicola Blanchard, 1885\u2009Apiosoma poteriformis Lom, 1966\u2009Order Mobilida\u2009Family Trichodinidae\u2009Trichodina cottidarum Dogiel, 1948\u2009Trichodina domerguei \u2009Trichodina gracilis Polyanskii, 1955\u2009Trichodina nigra Lom, 1960\u2009Trichodina sp.\u2009Tripartiella amurensis Phylum CiliophoraChilodonella cyprini Strand, 1928, was recorded from skin, buccal cavity, and gills of C. idella [ C. carpio [ H. molitrix [ C. cyprini in Iraq was from skin, buccal cavity, and gills of Mystus pelusius from Tigris River at Baghdad [. idella , 43, 51,. carpio , and skimolitrix , 43, 51. Baghdad . So far Baghdad .Ichthyophthirius multifiliis Fouquet, 1876, was recorded from skin and gills of C. idella [ C. carpio [ H. molitrix [ I. multifiliis in Iraq was from the skin and gills of Chelon subviridis (reported as Mugil dussumieri) from Tigris River near Baghdad [. idella , 51, 56,. carpio , 60, 65,molitrix , 47, 51. Baghdad . So far Baghdad .Apiosoma amoebae Lom, 1966, was reported from skin, buccal cavity, and gills of C. idella [ C. carpio [ H. molitrix [ A. amoebae was reported as Glossatella amoebae [ A. amoebae in Iraq was from the skin, buccal cavity, and gills of C. idella from Babylon Fish Farm [. idella , 24, 27,. carpio , and gilmolitrix , 27. It amoebae . The firish Farm . So far ish Farm .Apiosoma cylindriformis was reported from gills of C. idella [ C. carpio [ H. molitrix [ A. cylindriformis as Glossatella cylindriformis. The first record of A. cylindriformis in Iraq was from gills of C. idella and H. molitrix from Babylon Fish Farm [ A. cylindriformis has seven fish host species in Iraq [. idella , 24, 27,molitrix , 21, 27.ish Farm . So far, in Iraq .Apiosoma minuta Lom, 1966, was recorded from skin of C. carpio [ A. minuta has two fish host species in Iraq as it was recently recorded from Luciobarbus xanthopterus by Al-Salmany [. carpio , 47. Thi-Salmany .Apiosoma piscicola Blanchard, 1885, was recorded from skin, buccal cavity, and gills of C. idella [ C. carpio [ H. molitrix [ A. piscicola was reported as Glossatella piscicola [ A. piscicola was recorded for the first time in Iraq from skin, buccal cavity, and gills of C. idella, C. carpio and H. molitrix from Al-Suwaira and Al-Latifiya Fish Farms [. idella , 51, ski. carpio , 51, 55,molitrix , 29, 51.iscicola . A. piscsh Farms .Apiosoma poteriformis Lom, 1966, was recorded from skin and gills of C. idella [ C. carpio [ A. poteriformis was reported as Glossatella poteriformis by Al-Zubaidy [ A. poteriformis was recorded for the first time in Iraq from gills of C. idella from Babylon Fish Farm [. idella , 24, 27 ish Farm . So far,ish Farm .Trichodina cottidarum Dogiel, 1948, was recorded from skin and gills of C. carpio [ H. molitrix [ T. cottidarum was recorded for the first time in Iraq from gills of C. carpio from a manmade lake at Baghdad city [. carpio , 59, 60 molitrix , 47. T. dad city . So far,dad city .Trichodina domerguei was recorded from skin, fins, buccal cavity, and gills of C. idella [ C. carpio [ H. molitrix [ L. abu [ T. domerguei in Iraq was from skin, fins, and gills of eight freshwater fish species from Tigris River, Al-Tharthar Lake, and fish markets in Baghdad city [ T. domerguei has 39 host species in Iraq [. idella , 51, 56,. carpio , 56, 59,molitrix , 27, 51,[ L. abu , 56. Thedad city . So far, in Iraq and, theTrichodina gracilis Polyanskii, 1955, was recorded from skin of C. carpio [. carpio , 47. Thi. carpio .Trichodina nigra Lom, 1960, was recorded from skin and gills of the three carp species: C. idella [ C. carpio [ H. molitrix [ T. nigra in Iraq was from skin and gills of C. carpio and gills of H. molitrix from Babylon Fish Farm [ T. nigra has nine host species in Iraq [. idella , C. carp. carpio , 59, 60,molitrix , 29. Theish Farm . So far, in Iraq . Trichodina was recorded from L. abu [ Trichodina species so far recorded from fishes of Iraq, some unidentified species of Trichodina were so far recorded from six fish species [Unidentified specimen ofm L. abu with no species .Tripartiella amurensis was recorded from skin of C. carpio [ T. amurensis in Iraq [. carpio , 47. Thi in Iraq . Myxobilatus and four species to the genus Myxobolus. The phylum Myxozoa is represented in farm fishes of Babylon province with five species: one species belonged to the genus\u2009Class Myxosporea\u2009Order Bivalvulida\u2009Family Sphaerosporidae\u2009Myxobilatus legeri \u2009Family Myxobolidae\u2009Myxobolus dogieli Bykhovskaya-Pavlovskaya & Bykhovski, 1940\u2009Myxobolus muelleri B\u00fctschli, 1882\u2009Myxobolus oviformis Th\u00e9lohan, 1892\u2009Myxobolus pfeifferi Th\u00e9lohan, 1895 Phylum Myxozoa Myxobilatus legeri , erroneously reported as Myxobllatus legerl, with no given authority, description, and illustration, was recorded from skin and gills of C. carpio [ M. legeri in Iraq [. carpio . This wa in Iraq .Myxobolus dogieli Bykhovskaya-Pavlovskaya & Bykhovski, 1940, was recorded from kidneys and gallbladder of L. abu [ M. dogieli in Iraq was mainly from the external surface of heart, liver, and ovaries of L. abu from Tigris River at Baiji town [ M. dogieli has nine host species in Iraq [f L. abu . The firiji town . So far, in Iraq .Myxobolus muelleri B\u00fctschli, 1882, was recorded from intestine and liver of C. carpio [ m\u00fclleri. The first record of M. muelleri in Iraq was from gills of Luciobarbus xanthopterus, reported as B. xanthopterus [ M. muelleri has eight host species in Iraq [. carpio with thehopterus . So far, in Iraq .Myxobolus oviformis Th\u00e9lohan, 1892, was recorded from skin, intestine, and kidneys of C. carpio [ M. oviformis in Iraq was from gill arches and heart of four fish species [ M. oviformis has 20 fish host species in Iraq [. carpio , 54, 59. species . So far, in Iraq .Myxobolus pfeifferi Th\u00e9lohan, 1895, was recorded from gills, intestine, liver, kidneys, and gallbladder of C. idella [ C. carpio [ H. molitrix [ L. abu [ M. pfeifferi in Iraq was from gills of Acanthobrama marmid from Tigris River at Mosul city [ M. pfeifferi is the prevalent myxozoan among fishes of Iraq as it has 35 fish host species [. idella , gills, . carpio , 53, 59,molitrix , 29, and[ L. abu . The firsul city . So far, species . Apharyngostrigea and Ascocotyle and three species to the genus Diplostomum.The class Trematoda of the phylum Platyhelminthes is represented in farm fishes of Babylon province with five species; two species belonged to the genera\u2009Class Trematoda\u2009Order Diplostomida\u2009Family Strigeidae\u2009Apharyngostrigea cornu \u2009Family Diplostomidae\u2009Diplostomum indistinctum Hughes, 1929\u2009Diplostomum paraspathaceum Schigin, 1965\u2009Diplostomum spathaceum Olsson, 1876\u2009Order Plagiorchiida\u2009Family Heterophyidae\u2009Ascocotyle coleostoma Looss, 1899 Phylum Platyhelminthes Apharyngostrigea cornu was recorded as metacercaria from mesentery, coelom and liver of C. carpio [ A. cornu from fishes of Iraq [ Ardea purpurea in Bahr Al-Najaf Depression [. carpio . This wa of Iraq . The adupression .Ascocotyle coleostoma Looss, 1899, was recorded as metacercaria from gills of H. fossilis [ H. fossilis and L. abu from Diyala River [ A. coleostoma has so far 34 fish host species in Iraq [ A. coleostoma was detected from the grey heron A. cinerea in Babylon (now Al-Furat) Fish Farm [fossilis . This pala River . A. cole in Iraq . The aduish Farm .Diplostomum indistinctum Hughes, 1929, was recorded as metacercaria from eyes of H. molitrix [ D. indistinctum was from eyes of Luciobarbus esocinus, reported as B. esocinus from fish market in Mosul city [molitrix . The firsul city . No moresul city .Diplostomum paraspathaceum Schigin, 1965, was recorded as metacercaria from eyes of both C. idella [ C. carpio [. idella and C. c. carpio . This wa. carpio .Diplostomum spathaceum Olsson, 1876, was recorded as metacercaria from eyes of the three carp species: C. idella [ C. carpio [ H. molitrix [ D. spathaceum was from eyes of C. luteus, reported as B. luteus, Cyprinion macrostomum, and C. carpio from Dokan Lake [ Diplostomum spp. are responsible for worm cataract which causes fish blindness [ Larus argentatus in Bahr Al-Najaf Depression [. idella , 56, C. . carpio , 43, andkan Lake . Thirty-kan Lake . Metacer Gyrodactylus, 26 species of Dactylogyrus, and one species of each of the genera Pseudacolpenteron, Diplozoon, Eudiplozoon, Paradiplozoon, and Microcotyle in addition to some unidentified species of Dactylogyrus and Diplozoon. It is appropriate to mention here that this group is considered as Monogenea by some electronic sites [The class Monogenea of the phylum Platyhelminthes is represented in farm fishes of Babylon province with 45 species: 12 species of the genusic sites \u201312 but aic sites , 66. \u2009Class Monogenea\u2009Order Gyrodactylidea\u2009Family Gyrodactylidae\u2009Gyrodactylus baicalensis Bogolepova, 1950\u2009Gyrodactylus ctenopharngodontis Ling in Gusev, 1952\u2009Gyrodactylus elegans von Nordmann, 1832\u2009Gyrodactylus kherulensis Ergens, 1974\u2009Gyrodactylus macracanthus Hukuda, 1940\u2009Gyrodactylus malmbergi Ergens, 1961\u2009Gyrodactylus markevitschi Kulakovskaya, 1952\u2009Gyrodactylus medius Kathariner, 1895\u2009Gyrodactylus menschikowi Gvosdev, 1950\u2009Gyrodactylus salaris Malmberg, 1957\u2009Gyrodactylus sprostonae Ling, 1962\u2009Gyrodactylus vicinus Bychowsky, 1957\u2009Order Dactylogyridea\u2009Family Dactylogyridae\u2009Dactylogyrus achmerowi Gusev, 1955\u2009Dactylogyrus amurensis Akhmerov, 1952\u2009Dactylogyrus anchoratus Wagener, 1857\u2009Dactylogyrus arcuatus Yamaguti, 1942\u2009Dactylogyrus barbioides Gusev, Ali, Abdul-Ameer, Amin & Moln\u00e1r, 1993\u2009Dactylogyrus cornu Linstow, 1878\u2009Dactylogyrus crassus Kulwiec, 1927\u2009Dactylogyrus ctenopharyngodonis Achmerow, 1952\u2009Dactylogyrus dogieli Gusev, 1953\u2009Dactylogyrus ergensi Moln\u00e1r, 1964\u2009Dactylogyrus extensus Mueller & Van Cleave, 1932\u2009Dactylogyrus gobii Gvosdev, 1950\u2009Dactylogyrus hypophthalmichthys Akhmerov, 1952\u2009Dactylogyrus inexpectatus Izjumova, in Gusev, 1955\u2009Dactylogyrus jamansajensis Osmanov, 1958\u2009Dactylogyrus lamellatus Akhmerov, 1952\u2009Dactylogyrus latituba Gusev, 1955\u2009Dactylogyrus lopuchinae Jukhimenko, 1981\u2009Dactylogyrus minutus Kulwiec, 1927\u2009Dactylogyrus navicularis A. Gusev, 1955\u2009Dactylogyrus phoxini Malevitskaia, 1949\u2009Dactylogyrus propinquus Bychowsky, 1931\u2009Dactylogyrus sahuensis Ling in Chen et al., 1973\u2009Dactylogyrus simplex Bychowsky, 1936\u2009Dactylogyrus skrjabini Akhmerov, 1954\u2009Dactylogyrus vastator Nybelin, 1924\u2009Dactylogyrus spp.\u2009Pseudacolpenteron pavlovskii Bychowsky & Gussev, 1955\u2009Order Mazocraeidea\u2009Family Diplozoidae\u2009Diplozoon paradoxum Nordmann, 1832\u2009Diplozoon sp.\u2009Eudiplozoon nipponicum \u2009Paradiplozoon barbi \u2009Family Microcotylidae\u2009Microcotyle donavini van Beneden & Hesse, 1863 Phylum PlatyhelminthesGyrodactylus baicalensis Bogolepova, 1950, was recorded from skin, fins, and gills of C. carpio [ G. baicalensis in Iraq was from skin, buccal cavity, and gills of C. carpio from Al-Suwaira and Al-Latifiya Fish Farms [ G. baicalensis has eight fish host species in Iraq [. carpio , 29, 52. in Iraq .Gyrodactylus ctenopharngodontis Ling in Gusev, 1952, was recorded from skin, fins, buccal cavity, and gills of C. idella [ G. ctenopharngodontis in Iraq was from gills of C. idella from Babylon Fish Farm [. idella , 27. Theish Farm . No moreish Farm .Gyrodactylus elegans von Nordmann, 1832, was recorded from skin, fins, buccal cavity, and gills of both C. idella [ C. carpio [ H. molitrix [ L. abu [ G. elegans in Iraq was from C. carpio from Al-Zaafaraniya Fish Farm and L. abu from Al-Latifiya Fish Farm [ G. elegans has 23 fish host species in Iraq [. idella , 29, 52 . carpio , 56, 60 [ L. abu with no ish Farm . So far, in Iraq .Gyrodactylus kherulensis Ergens, 1974, was recorded from skin and gills of C. idella [ C. carpio [ G. kherulensis in Iraq was from gills of C. carpio from Babylon Fish Farm [ G. kherulensis has four fish host species in Iraq [. idella and skin. carpio , 27. Theish Farm . So far, in Iraq .Gyrodactylus macracanthus Hukuda, 1940 , was recorded from skin and gills of C. carpio [ H. molitrix [ G. paralatus also. According to Gussev [ G. paralatus is a synonym of G. macracanthus. No more hosts are so far known for G. macracanthus or its synonym G. paralatus from fishes of Iraq [. carpio and skinmolitrix . This wamolitrix as G. pao Gussev and Pugao Gussev , G. para of Iraq .Gyrodactylus malmbergi Ergens, 1961, was recorded from skin, fins, and gills of C. carpio [ H. molitrix [ G. malmbergi from fishes of Iraq [. carpio and frommolitrix . This wa of Iraq .Gyrodactylus markevitschi Kulakovskaya, 1952, was recorded from skin and gills of C. carpio [ Capoeta trutta (reported as Varicorhinus trutta) from Tigris River at Baiji town [ G. markevitschi has six host species in Iraq [. carpio , 47, 60.iji town . So far, in Iraq .Gyrodactylus medius Kathariner, 1895, was recorded from skin and fins of C. carpio [. carpio . This wa. carpio as well . carpio . Also th. carpio . Now, th. carpio .Gyrodactylus menschikowi Gvosdev, 1950, was recorded from skin and gills of C. carpio [ C. carpio and skin, fins, and gills of L. abu both from Hilla River [. carpio . The firla River . So far,la River .Gyrodactylus salaris Malmberg, 1957, was recorded from skin and gills of C. carpio [ C. carpio from Al-Furat Fish Farm [. carpio , 29. Theish Farm . The yeaish Farm and Al-Jish Farm .Gyrodactylus sprostonae Ling, 1962, was recorded fromskin and fins of C. carpio [. carpio . This wa. carpio .Gyrodactylus vicinus Bychowsky, 1957, was recorded from skin, fins, and gills of C. carpio [ C. carpio from Al-Furat Fish Farm [. carpio , 35. Theish Farm . Now, itish Farm . Gyrodactylus species reported from C. carpio [ Gyrodactylus species [Finally, the unidentified. carpio , 38 were. carpio . In Iraq species .Dactylogyrus achmerowi Gusev, 1955, was recorded from gills of C. carpio [ D. achmerowi in Iraq was from gills of C. carpio from Al-Wahda Fish Hatchery at Al-Suwaira and Babylon Fish Farm [. carpio , 55, 60.ish Farm .Dactylogyrus amurensis Akhmerov, 1952, was recorded from gills of C. carpio [. carpio . This wa. carpio .Dactylogyrus anchoratus Wagener, 1857, was recorded from gills of C. carpio [ D. anchoratus in Iraq were from gills of C. carpio from Tigris River at Al-Zaafaraniya [. carpio . The firfaraniya . Now, itfaraniya .Dactylogyrus arcuatus Yamaguti, 1942, was recorded from gills of C. idella [ C. carpio [ D. arcuatus in Iraq was from skin, buccal cavity, and gills of C. carpio from Al-Suwaira and Al-Latifiya Fish Farms [. idella and skin. carpio , 59, 60.sh Farms . Now, itsh Farms .Dactylogyrus barbioides Gusev, Ali, Abdul-Ameer, Amin & Moln\u00e1r, 1993, was recorded from gills of C. carpio [ D. barbioides was described as a new species from gills of Barbus grypus from Tigris River near Baiji town [. carpio . D. barbiji town . Now, itiji town .Dactylogyrus cornu Linstow, 1878, was recorded from gills of C. carpio [ D. cornu was recorded for the first time in Iraq from gills of five fish species from Diyala River [. carpio , 59. D. la River . So far,la River .Dactylogyrus crassus Kulwiec, 1927, was recorded from gills of C. carpio [ D. crassus was recorded for the first time in Iraq from gills of C. carpio from Al-Shark Al-Awsat Fish Farm [ crassus was misspelled as carassus by Al-Rubaie et al. [. carpio , 55, 60.ish Farm . It is ae et al. .Dactylogyrus ctenopharyngodonis Achmerow, 1952, was recorded from gills of C. idella from Al-Shark Al-Awsat Fish Farm [ D. ctenopharyngodonis in fishes of Iraq [ish Farm . This is of Iraq .Dactylogyrus dogieli Gusev, 1953, was recorded from gills of C. carpio in fish cages and an earthen pond in Sadat Al-Hindiya [ D. dogieli was from five fish species from Euphrates River at Al-Musaib city [ D. dogieli in Iraq [-Hindiya . The firaib city and its aib city . Six hos in Iraq .Dactylogyrus ergensi Moln\u00e1r, 1964, was recorded from gills of C. carpio from Al-Furat Fish Farm [ D. ergensi in Iraq [ish Farm . This wa in Iraq .Dactylogyrus extensus Mueller & Van Cleave, 1932, was recorded from gills of C. idella [ C. carpio [ H. molitrix [ D. extensus in Iraq was from the buccal cavity and gills of C. carpio from Al-Suwaira and Al-Latifiya Fish Farms [ D. solidus which was also recorded from the same host by Salih et al. [ D. extensus according to Gibson et al. [ D. extensus and its synonym D. solidus have so far 17 fish host species in Iraq [. idella , buccal . carpio , 59, 60,molitrix , 45, 47.sh Farms . D. solih et al. as well h et al. and Al-Rh et al. is consin et al. . D. exteDactylogyrus gobii Gvosdev, 1950, was recorded from skin and gills of C. carpio [ D. gobii was recorded for the first time in Iraq from gills of C. carpio from Al-Shark Al-Awsat Fish Farm [. carpio , 47, 60.ish Farm . Now, itish Farm .Dactylogyrus hypophthalmichthys Akhmerov, 1952, was recorded from skin, buccal cavity, and gills of H. molitrix [ D. hypophthalmichthys was reported as Neodactylogyrus hypophthalmichthys by Asmar et al. [ D. hypophthalmichthys in Iraq was from the buccal cavity and gills of H. molitrix from Al-Suwaira and Al-Latifiya Fish Farms [ H. molitrix is the only host so far known for D. hypophthalmichthys in Iraq [molitrix , 52, 56. in Iraq .Dactylogyrus inexpectatus Izjumova, in Gusev, 1955, was recorded from skin and gills of C. idella [ C. carpio [ H. molitrix [ D. inexpectatus in Iraq was from skin and gills of C. idella from Al-Suwaira and Al-Latifiya Fish Farms [. idella , 29, 52,. carpio , 29, andsh Farms .Dactylogyrus jamansajensis Osmanov, 1958, was recorded from gills of C. carpio [ D. jamansajensis in Iraq was from gills of C. luteus from manmade lakes, north of Baghdad [. carpio , 47. The Baghdad . Now, it Baghdad .Dactylogyrus lamellatus Akhmerov, 1952, was recorded from skin, fins, buccal cavity, and gills of C. idella [ C. carpio [ D. lamellatus in Iraq was from the skin, buccal cavity, and gills of C. idella from Al-Suwaira and Al-Latifiya Fish Farms [. idella , 52, 56 . carpio . The firsh Farms .Dactylogyrus latituba Gusev, 1955, was recorded from gills of both C. idella [ C. carpio [ H. molitrix [ D. latituba in Iraq was from gills of C. luteus from manmade lakes, north of Baghdad [. idella and C. c. carpio , 27 as w Baghdad . Now, it Baghdad .Dactylogyrus lopuchinae Jukhimenko, 1981, was recorded from gills of C. carpio [ D. lopuchinae was recorded for the first time in Iraq from gills of C. carpio from Al-Shark Al-Awsat Fish Farm [. carpio , 47, 54.ish Farm . No moreish Farm .Dactylogyrus minutus Kulwiec, 1927, was recorded from skin, fins, and gills of C. carpio [ C. carpio from Tigris River at Al-Zaafaraniya, south of Baghdad, and Al-Qadisia Dam Lake [ D. minutus has 12 fish species in Iraq [. carpio , 59, 60.Dam Lake , while iDam Lake . So far, in Iraq .Dactylogyrus navicularis A. Gusev, 1955, was recorded from fins, buccal cavity, and gills of C. carpio [ D. navicularis in Iraq was from the buccal cavity, fins, and gills of C. carpio from Al-Furat Fish Farm [ C. carpio is the only host so far known for D. navicularis in Iraq [. carpio , 35, 60.ish Farm . C. carp in Iraq .Dactylogyrus phoxini Malevitskaia, 1949, was recorded from skin and gills of C. carpio [ D. phoxini in Iraq was in June 1995 from gills of C. carpio from Tigris River at Al-Zaafaraniya but the report was published later by Balasem et al. [. carpio , 47, 60.m et al. . This pam et al. .Dactylogyrus propinquus Bychowsky, 1931, was recorded from gills of C. carpio [ D. propinquus in Iraq was from gills of C. carpio from Al-Furat Fish Farm [ C. carpio is the only host so far known for D. propinquus in Iraq [. carpio , 35, 49.ish Farm . C. carp in Iraq .Dactylogyrus sahuensis Ling in Chen et al., 1973, was recorded from fins and gills of C. carpio [ D. sahuensis in Iraq was from fins and gills of C. carpio from Al-Furat Fish Farm [ C. carpio is the only host so far known for D. sahuensis in Iraq [. carpio . The firish Farm . C. carp in Iraq .Dactylogyrus simplex Bychowsky, 1936, was recorded from C. carpio [ D. simplex in Iraq was from gills of C. carpio from the new fish farm of the Fish Research Center at Al-Zaafaraniya [ D. simplex has so far three host species in Iraq [. carpio with no in Iraq .Dactylogyrus skrjabini Akhmerov, 1954, was recorded from buccal cavity and gills of C. carpio [ H. molitrix [ D. skrjabini in Iraq was from buccal cavity and gills of H. molitrix from Al-Suwaira and Al-Latifiya Fish Farms [ D. skrjabini has six host species in Iraq [. carpio , 45, 47 molitrix , 27, 52. in Iraq .Dactylogyrus vastator Nybelin, 1924, was recorded from gills of C. idella [ C. carpio [ D. vastator from Iraq was from skin and gills of C. macrostomum from Tigris River at Baghdad [ D. vastator was reported from 33 fish host species from north, middle, and south of Iraq [. idella and skin. carpio , 60, 64. Baghdad . So far, of Iraq . Dactylogyrus species were recorded from skin and gills of C. idella [ C. carpio [ Dactylogyrus species of Al-Zubaidy et al. [ Dactylogyrus species [Unidentified. idella and from. carpio , 38, 56.y et al. , 38 werey et al. . In Iraq species .Pseudacolpenteron pavlovskii Bychowsky & Gussev, 1955, was recorded from fins and gills of C. carpio [ H. molitrix [ P. pavlovskii from Iraq was from skin and gills of C. carpio from Babylon Fish Farm [. carpio , 45, 47 molitrix . The firish Farm . This spish Farm .Diplozoon paradoxum Nordmann, 1832, was recorded from gills of C. carpio [ Carasobarbus luteus, reported as Barbus luteus, from Al-Husainia creek, Karbala province [. carpio . This paprovince . Now, itprovince . Diplozoon species were recorded from gills of C. carpio [ Diplozoon species occurred as larvae in 12 fish host species in Iraq [Unidentified. carpio . Some ot in Iraq .Eudiplozoon nipponicum was recorded from gills of C. carpio [ C. carpio from a manmade lake in Baghdad [ Diplozoon nipponicum but then it was reported by its valid name E. nipponicum by all subsequent researchers. So far, three host species are known for E. nipponicum in Iraq [. carpio . This pa Baghdad as Diplo in Iraq .Paradiplozoon barbi was recorded from gills of C. carpio [ Diplozoon barbi. This parasite was reported for the first time in Iraq from gills of Chondrostoma nasus, C. regium, and C. carpio from Tigris River at Baghdad\u2009\u2009[ Diplozoon barbi. Also, all the subsequent records in the Iraqi literature, except the checklists of Mhaisen and Abdul-Ameer [ D. barbi. According to Khotenovsky [ D. barbi is a synonym of P. barbi. Eight host species are so far known for this parasite in Iraq [. carpio as DiploBaghdad\u2009\u2009 as Diploul-Ameer , referretenovsky , D. barb in Iraq .Microcotyle donavini van Beneden & Hesse, 1863, was recorded from gills of L. abu from Babylon Fish Farm [ M. donavini in Iraq [ish Farm . This wa in Iraq . Bothriocephalus, Ligula, and Neogryporhynchus as well as two species of Proteocephalus. The class Cestoda of the phylum Platyhelminthes is represented in farm fishes of Babylon province with five species: one species of each of the genera\u2009Class Cestoda\u2009Order Bothriocephalidea\u2009Family Bothriocephalidae\u2009Bothriocephalus acheilognathi Yamaguti, 1934\u2009Order Diphyllobothriidea\u2009Family Diphyllobothriidae\u2009Ligula intestinalis Bloch, 1782\u2009Order Proteocephalidea\u2009Family Proteocephalidae\u2009Proteocephalus osculatus Nybelin, 1942\u2009Proteocephalus torulosus Nufer, 1905\u2009Order Cyclophyllidea\u2009Family Dilepididae\u2009Neogryporhynchus cheilancristrotus Baer & Bona, 1960 Phylum PlatyhelminthesBothriocephalus acheilognathi Yamaguti, 1934, was recorded from the intestine of both C. idella [ C. carpio [ B. opsariichthydis by Salih et al. [ B. acheilognathi in Iraq was from the intestine of C. carpio from different fish farms near Baghdad [ Bothriocephalus, B. gowkongensis Yeh, 1955, and B. opsariichthydis Yamaguti, 1934, were also reported from Iraq [ B. acheilognathi. At the present time, B. acheilognathi and both of its above-named synonyms has so far a total of 21 host species in Iraq [. idella , 56 and . carpio , 53, 62.h et al. and Al-Zh et al. . The fir Baghdad . Two othrom Iraq . Accordirom Iraq , both th in Iraq .Ligula intestinalis Bloch, 1782, was recorded from the body cavity of both C. idella [ C. carpio [ L. intestinalis was reported for the first time in Iraq as a plerocercoid from the body cavity of Leuciscus vorax (reported as A. vorax) from Shatt Al-Arab River [ L. intestinalis was reported from the intestine of the moorhen Gallinula chloropus chloropus from around Baghdad [. idella , 27, 29 ab River . So far,alis L., 58 Bloch, Baghdad .Proteocephalus osculatus Nybelin, 1942, was recorded from the intestine of C. carpio [ L. vorax (reported as A. vorax) from Al-Tharthar Lake [. carpio . The firhar Lake . So far,s Goeze, 82 NybeliProteocephalus torulosus Nufer, 1905, was recorded from intestine of C. carpio [ C. carpio from a fish farm near Baghdad city [. carpio . The firdad city . So far, Batsch, 86 Nufer,Neogryporhynchus cheilancristrotus Baer & Bona, 1960, was recorded from the intestine of C. carpio by Al-Zubaidy [ Gryporhynchus cheilancristrotus. The first report of N. cheilancristrotus in Iraq was from the intestine of L. abu from Diyala River [-Zubaidy as Grypola River . So far,la River . Contracaecum as well as one species of each of the genera Cucullanus and Rhabdochona.The phylum Nematoda is represented in farm fishes of Babylon province with three species: unidentified larval species of the genus\u2009Class Secernentea\u2009Order Ascaridida\u2009Family Anisakidae\u2009Contracaecum spp.\u2009Family Cucullanidae\u2009Cucullanus cyprini Yamaguti, 1941\u2009Order Spirurida\u2009Family Rhabdochonidae\u2009Rhabdochona hellichi Phylum Nematoda Contracaecum was recorded from the intestinal wall, body cavity, liver, spleen, heart, and gonads of C. carpio [ L. abu [ Contracaecum spp. larvae in Iraq was from the body cavity and different viscera of 10 fish species from different inland waters of Iraq [ Contracaecum spp. larvae have so far 40 fish host species in Iraq [ Contracaecum spp. were detected from six species of aquatic birds in Iraq, Egretta alba, E. garzetta, Ardeola ralloides, Botaurus stellaris, Ardea purpurea, and Ceryle rudis, from Bahr Al-Najaf Depression [Unidentified larval species of. carpio , 29 and [ L. abu , 37, 42. of Iraq . Contrac in Iraq . Adult wpression .Cucullanus cyprini Yamaguti, 1941, was recorded from the intestine of C. carpio [ Alburnus caeruleus and Luciobarbus xanthopterus (reported as B. xanthopterus) from Al-Tharthar Lake [. carpio . The firhar Lake . So far,har Lake .Rhabdochona hellichi , erroneously reported as R. bellichi, was recorded from intestine of the three carp species: C. idella [ C. carpio [ H. molitrix [ R. bellichi) from the intestine and coelom of L. xanthopterus (reported as B. xanthopterus), H. fossilis, and Mystus pelusius . Eight fish species are so far known for this parasite in Iraq [. idella , C. carp. carpio , and H. molitrix . Ali et molitrix reported in Iraq . Neoechinorhynchus. The phylum Acanthocephala is represented in farm fishes of Babylon province with two valid species of the genus\u2009Class Eoacanthocephala\u2009Order Neoechinorhynchida\u2009Family Neoechinorhynchidae\u2009Neoechinorhynchus iraqensis Amin, Al-Sady, Mhaisen & Bassat, 2001\u2009Neoechinorhynchus rutili Hamann, 1892 Phylum AcanthocephalaNeoechinorhynchus iraqensis Amin, Al-Sady, Mhaisen & Bassat, 2001, was recorded from intestine of both C. carpio [ L. abu [ N. agilis from C. carpio and L. abu by Al-Zubaidy [ N. agilis is a misidentification of N. iraqensis [ N. iraqensis was as species de novo from the intestine of L. abu from the Euphrates River at Al-Fallujah region [ N. iraqensis and the misidentified N. agilis have so far 24 fish host species in Iraq [. carpio and L. a[ L. abu , 50. It -Zubaidy and Ali -Zubaidy , respectraqensis . The firh region , while ih region . N. iraq in Iraq .Neoechinorhynchus rutili Hamann, 1892, was recorded from the intestine of the three carp species: C. idella [ C. carpio [ H. molitrix [ N. rutili was firstly recorded by Herzog [ L. xanthopterus (reported as B. xanthopterus) from Tigris and Diyala rivers near Baghdad and from L. abu (reported as Mugil abu) from Citscher Oasis near Al-Fallujah. N. rutili has so far 16 fish host species in Iraq [. idella , C. carp. carpio , 29, andy Herzog from L. M\u00fcller, 80 Hamann Argulus, Dermoergasilus, Paraergasilus, Lamproglena, and Lernaea and three species of Ergasilus in addition to unidentified species of Ergasilus.\u2009\u2009The subphylum Crustacea of the phylum Arthropoda is represented in farm fishes of Babylon province with nine species: one species of each of the genera\u2009Subphylum Crustacea\u2009Class Maxillopoda\u2009Order Arguloida\u2009Family Argulidae\u2009 Argulus foliaceus \u2009Order Cyclopoida\u2009Family Ergasilidae\u2009 Dermoergasilus varicoleus Ho, Jayarajan & Radhakrishnan, 1992\u2009 Ergasilus barbi Rahemo, 1982\u2009 Ergasilus mosulensis Rahemo, 1982\u2009 Ergasilus sieboldi von Nordmann, 1832\u2009 Ergasilus sp.\u2009 Paraergasilus inflatus Ho, Khamees & Mhaisen, 1996\u2009Family Lernaeidae\u2009Lamproglena pulchella von Nordmann, 1832\u2009 Lernaea cyprinacea L., 1758 Phylum ArthropodaArgulus foliaceus was recorded from gills of the three carp species: C. idella [ C. carpio [ H. molitrix [ C. auratus [ A. foliaceus was reported for the first time in Iraq [ C. carpio from Al-Zaafaraniya Fish-Culture Station and C. luteus (reported as B. luteus) from Al-Habbaniyah Lake [ A. foliaceus has so far 16 fish host species in Iraq [. idella , C. carp. carpio , 27, andus L., 17 was reco in Iraq from skiyah Lake . A. foliDermoergasilus varicoleus Ho, Jayarajan & Radhakrishnan, 1992, was recorded from gills of L. abu [ L. abu from Shatt Al-Arab River [ D. varicoleus has so far nine fish host species in Iraq [f L. abu , 40. Thiab River . D. vari in Iraq .Ergasilus barbi Rahemo, 1982, was recorded from gills of L. abu [ B. grypus from Tigris River at Mosul city by Fattohy [ E. barbi has so far 13 fish host species in Iraq [f L. abu . This cr Fattohy and its Fattohy . E. barb in Iraq .Ergasilus mosulensis Rahemo, 1982, was recorded from gills of the three carp species, C. idella [ C. carpio [ H. molitrix [ L. abu [ L. abu from Tigris River at Mosul city by Fattohy [ E. mosulensis has so far 23 fish host species in Iraq [. idella , C. carp. carpio , and H. molitrix as well [ L. abu . This cr Fattohy and its Fattohy . E. mosu in Iraq .Ergasilus sieboldi von Nordmann, 1832, was recorded from gills, buccal cavity, and skin of the three carp species: C. idella [ C. carpio [ H. molitrix [ E. sieboldi in Iraq was from gills of L. vorax (reported as A. vorax) from Al-Habbaniyah Lake [ E. sieboldi has so far 26 fish host species in Iraq [. idella , 29, C. . carpio , 55, andmolitrix , 29, 56.yah Lake . E. sieb in Iraq .Ergasilus sp. was recorded from L. abu [ Ergasilus so far recorded from fishes of Iraq, some specimens of unidentified Ergasilus species were also reported from 12 fish species in Iraq [m L. abu with no in Iraq .Paraergasilus inflatus Ho, Khamees & Mhaisen, 1996, was recorded from gills of H. molitrix [ L. abu from Shatt Al-Arab River [ D. varicoleus has so far seven fish host species in Iraq [molitrix . This crab River . D. vari in Iraq .Lamproglena pulchella von Nordmann, 1832, was recorded from gills of C. carpio [ L. pulchella in Iraq was from gills of Chondrostoma regium and Capoeta trutta (reported as Varicorhinus trutta) from Tigris River at Mosul city [ L. pulchella has so far 19 fish host species in Iraq [. carpio . The firsul city . L. pulc in Iraq .Lernaea cyprinacea L., 1758, was recorded from skin, fins, and gills of the three carp species, C. idella [ C. carpio [ H. molitrix [ L. abu [ L. cyprinacea in Iraq was from skin, fins, buccal cavity, pharyngeal cavity, gills, and anus of seven freshwater fish species from Al-Zaafaraniya Fish-Culture Station [ L. cyprinacea is the commonest crustacean among fishes of Iraq as it has so far 30 fish host species in Iraq [. idella , 43, 51,. carpio , 61, 63,molitrix \u201329, 43, [ L. abu . The fir Station . L. cypr Unio. The systematic account of this parasite, followed by parasite-host list, is given here. The phylum Mollusca is represented in farm fishes of Babylon province with only one parasite species of the genus\u2009Class Bivalvia\u2009Order Unionoida\u2009Family Unionidae\u2009Unio pictorum Phylum MolluscaUnio pictorum was recorded from gills of both C. carpio [ H. molitrix [ U. pictorum in Iraq was from gills of eight freshwater fish species from Diyala River [ U. pictorum was erroneously stated as Zhadin, 1938, in all the Iraqi literature except Al-Salmany [ U. pictorum has so far 24 fish host species in Iraq [. carpio , 29 and molitrix . The firla River . It is a-Salmany . U. pictThe following host-parasite list for fish parasites in fish farms of Babylon province is compiled. For each host, the scientific names of all recorded parasites are alphabetically enlisted under their major parasitic groups. To economize space, references of previous records for each parasite species are not given here. These can be obtained from the account of each concerned parasite species in the part of major groups of parasitic fauna within the results and discussion part.\u2009 Ichthyobodo necator.Mastigophora:\u2009 Eimeria dogieli, E. mylopharyngodoni, and Haemogregarina sp.Apicomplexa:\u2009 Apiosoma amoebae, A. cylindriformis, A. minuta, A. piscicola, A. poteriformis, Chilodonella cyprini, Ichthyophthirius multifiliis, Trichodina cottidarum, T. domerguei, T. gracilis, T. nigra, and Tripartiella amurensis.Ciliophora:\u2009 Myxobilatus legeri, Myxobolus muelleri, M. oviformis, and M. pfeifferi.Myxozoa:\u2009 Apharyngostrigea cornu, Diplostomum paraspathaceum, and D. spathaceum.Trematoda:\u2009 Dactylogyrus achmerowi, D. amurensis, D. anchoratus, D. arcuatus, D. barbioides, D. cornu, D. crassus, D. dogieli, D. ergensi, D. extensus, D. gobii, D. inexpectatus, D. jamansajensis, D. lamellatus, D. latituba, D. lopuchinae, D. minutus, D. navicularis, D. phoxini, D. propinquus, D. sahuensis, D. simplex, D. skrjabini, D. vastator, Dactylogyrus spp., Diplozoon paradoxum, Diplozoon sp., Eudiplozoon nipponicum, Gyrodactylus baicalensis, G. elegans, G. kherulensis, G. macracanthus, G. malmbergi, G. markewitschi, G. medius, G. menschikowi, G. salaris, G. sprostonae, G. vicinus, Paradiplozoon barbi, and Pseudacolpenteron pavlovskii.Monogenea:\u2009 Bothriocephalus acheilognathi, Ligula intestinalis, Neogryporhynchus cheilancristrotus, Proteocephalus osculatus, and P. torulosus.Cestoda:\u2009 Contracaecum sp., Cucullanus cyprini, and Rhabdochona hellichi.Nematoda:\u2009 Neoechinorhynchus iraqensis and N. rutili.Acanthocephala:\u2009 Argulus foliaceus, Ergasilus mosulensis, E. sieboldi, Lamproglena pulchella, and Lernaea cyprinacea.Crustacea:\u2009 Unio pictorum.Mollusca:\u2009 Apiosoma amoebae, A. cylindriformis, A. piscicola, A. poteriformis, Chilodonella cyprini, Ichthyophthirius multifiliis, Trichodina domerguei, and T. nigra.Ciliophora:\u2009 Myxobolus pfeifferi.Myxozoa:\u2009 Diplostomum paraspathaceum and D. spathaceum.Trematoda:\u2009 Dactylogyrus arcuatus, D. ctenopharyngodonis, D. extensus, D. inexpectatus, D. lamellatus, D. latituba, D. vastator, Dactylogyrus sp., Gyrodactylus ctenopharyngodontis, G. elegans, and G. kherulensis.Monogenea:\u2009 Bothriocephalus acheilognathi and Ligula intestinalis.Cestoda:\u2009 Rhabdochona hellichi.Nematoda:\u2009 Neoechinorhynchus rutili.Acanthocephala:\u2009 Argulus foliaceus, Ergasilus mosulensis, E. sieboldi, and Lernaea cyprinacea.Crustacea:\u2009 Apiosoma amoebae, A. cylindriformis, A. piscicola, Chilodonella cyprini, Ichthyophthirius multifiliis, Trichodina cottidarum, T. domerguei, and T. nigra.Ciliophora:\u2009 Myxobolus pfeifferi.Myxozoa:\u2009 Diplostomum indistinctum and D. spathaceum.Trematoda:\u2009 Dactylogyrus extensus, D. hypophthalmichthys, D. inexpectatus, D. latituba, D. skrjabini, Gyrodactylus elegans, G. macracanthus, G. malmbergi, and Pseudacolpenteron pavlovskii.Monogenea:\u2009 Rhabdochona hellichi.Nematoda:\u2009 Neoechinorhynchus rutili.Acanthocephala:\u2009 Argulus foliaceus, Ergasilus mosulensis, E. sieboldi, Lernaea cyprinacea, and Paraergasilus inflatus.Crustacea:\u2009 Unio pictorum.Mollusca:\u2009 Argulus foliaceus.Crustacea:\u2009 Ascocotyle coleostoma.Trematoda:\u2009 Trichodina domerguei and Trichodina sp.Ciliophora:\u2009 Myxobolus dogieli and M. pfeifferi.Myxozoa:\u2009 Gyrodactylus elegans and Microcotyle donavini.Monogenea:\u2009 Contracaecum sp.Nematoda:\u2009 Neoechinorhynchus iraqensis.Acanthocephala:\u2009 Dermoergasilus varicoleus, Ergasilus barbi, E. mosulensis, Ergasilus sp., and Lernaea cyprinacea.Crustacea:"} +{"text": "The following conflict of interest statement should be added:Volume 7, no. 2, doi:All authors except K.C.H. are or have been employees of bioM\u00e9rieux, Inc. (L.B. has since retired). We have no other conflicts of interest to declare."} +{"text": "The sixth author, Pamela R. Hall, should not have been attributed equal contribution with John P. O\u2019Rourke and Seth M. Daly."} +{"text": "The third author is listed incorrectly in the citation for this article. The correct citation is given below.10.1371/journal.pone.0116926Sendlhofer G, Mosbacher N, Leitgeb K, Kober B, Jantscher L, Berghold A, et al. (2015) Implementation of a Surgical Safety Checklist: Interventions to Optimize the Process and Hints to Increase Compliance. PLoS ONE 10(2): e0116926. doi:"} +{"text": "There was an error in the Biology Open article doi:10.1242/bio.017400 published ahead of print on 23 March 2016.The author list was incomplete, and the text highlighted in bold below has been changed in the author list, the author affiliations and the author contribution sections:1,*, Marcel Westenberg1,\u2021, Paul T. Seed2, 1,\u00a7Mark I.R. Petalcorin and Colin T. Dolphin1,\u00b6Nisha Hirani1Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. 2Division of Women's Health, King's College London, St Thomas\u2019 Hospital, London SE1 7EH, UK. *Present address: The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. \u2021Present address: Dutch National Plant Protection Organization (NPPO-NL), National Reference Centre, P.O. Box\u00a09102, Wageningen 6700 HC, The Netherlands. \u00a7Present address: PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Jalan Tungku Link, BE1410, Brunei Darussalam.\u00b6Author for correspondence (colin.dolphin@kcl.ac.uk)Author contributionsN.H., M.W. and M.I.R.P. undertook the generation of constructs, C. elegans husbandry, molecular genetic and phenotype analysis studies and microscopy. P.T.S. performed the statistical analysis. C.T.D. designed the experiments, participated in the experimental work and wrote the manuscript.Biology Open and the authors apologise to the readers for any confusion that this omission might have caused."} +{"text": "Scientific Reports6: Article number: 23092; 10.1038/srep23092 published online: 03152016; updated: 05202016.Mark Ellis was omitted from the author list in the original version of this Article. In addition, there was a typographical error in the spelling of the author Kai Sonder which was incorrectly given as Kai Sonders. These errors have been corrected in the PDF and HTML versions of the Article.The Acknowledgements section now reads:The authors duly acknowledge the financial support received from Mexico\u2019s Secretariat of Agriculture, Livestock, Rural Development, Fisheries and Food (SAGARPA) through the Seeds of Discovery-Sustainable Modernization of Traditional Agriculture project (Mas-Agro). We acknowledge Diversity Array Technology (DArT), Canberra, Australia, for the genotyping service provided. Authors extend sincere thanks to Drs Kanwarpal Singh Dhugga, Julio Huerta-Espino, Ky Mathews, Dave Marshall. The direct and indirect support of research technicians is duly acknowledged. We extend our special thanks to Seeds of Discovery project leader and Director of the Genetic Resources Program, Dr. Kevin Pixley, for his valuable support and encouragement to the team.The Author Contributions section now reads:S.S. and P.V. conceived and designed the experiments; J.F., J.B., H.L., P.V., D.S. and C.S. performed the diversity, statistical and association analyses; C.S.P., M.R. and M.T. carried out large scale evaluation for heat-drought; C.G. evaluated landraces for grain quality; S.S., C.O., C.P.S. M.E and P.W. contributed to Genotyping; K.S. performed climate data analysis and prepared maps; G.F.D., P.S., A.S., N.S.B., G.P.S., P.V. and S.S. screened core set for diseases; T.P. provided seed material from gene bank; J.C. and S.S. were in-charge to oversee the data collection and analyses; P.V. and S.S. wrote the manuscript and other authors contributed later on; and all authors reviewed the manuscript."} +{"text": "In Table S2, column #13 (\u2018BETA') is incorrect. A corrected version of Table S2 can be viewed below.Table S2eQTL SNP replication table. Summary of eQTL findings and replication across all included studies. eQTL SNPs were included in the table if, from a given study, they were the most highly associated cis-linked SNP within an LD block and if their 1. REF STUDY. eQTL discovery study.2. GENE. RefSeq gene identifier.3. CHR. Chromosome of the eQTL SNP and associated gene expression trait.4. STRAND. Annotated strand of the associated transcript.5. TSS. Genomic coordinate of the transcription start site.6. TES. Genomic coordinate of the transcription end site.7. RSID. Identity of the eQTL SNP.8. HS INDEX. Identity of the LD block containing the SNP.9. RSCOORD. Genomic coordinate of the SNP.10. TIER. Tier of the SNP with respect the associated gene.11. UBF. Univariate 12. MBF. Multivariate 13. BETA. Estimate of the effect size per minor allele of the SNP.14. GEX. Mean gene expression level across all samples in the discovery study.15. PROBE MAF. Maximum minor allele frequency of SNPs overlapping the coordinates of the gene expression probe.16. NALN. Number of high quality alignments between the gene expression probe and hg18.17. STL, MBR, CLI, CPL, HVC, GCT, GCF, HCE, HPC, MLI, GCL. Each subsequent column denotes the measure of univariate replication between the SNP and gene expression trait in the study set indicated by the TLA, where:Click here for additional data file."} +{"text": "Scientific Reports6: Article number: 1983410.1038/srep19834; published online: 01252016; updated: 02252016.B\u00e1lint N\u00e1fr\u00e1di was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article.The Author Contributions section now reads:L.F. initiated the research. E.H. synthesized the perovskite solutions and discovered the graphoepitaxial nanowire growth. M.S. and E.B. prepared the microfabricated devices. M.S., E.B. and B.N. performed the photocurrent measurements and analyzed the data. A.S. performed and analyzed the fluorescence measurements. E.H., A.S., M.S., E.B., B.N. and L.F. discussed the results and implications and commented on the manuscript at all stages."} +{"text": "Xanthomonas oryzae pv. oryzae virulence identified in West Africa,\u201d authored by Onasanya Amos, M. M. Ekperigin, A. Afolabi, R. O. Onasanya, Abiodun A. Ojo and I. Ingelbrecht, published in International Journal of Genetics and Molecular Biology, August 2013 (DOI: 10.5897/IJGMB2013.0070) (see [This article has been retracted as it is essentially identical in content with the published article titled \u201cTwo genotypes of"} +{"text": "Respiratory dysfunction is prevalent in critically ill patients and can lead to adverse clinical outcomes, including respiratory failure and increased mortality. Respiratory muscles, which normally sustain respiration through inspiratory muscle contractions, become weakened during critical illness, and recent studies suggest that respiratory muscle weakness is related to systemic inflammation. Here, we investigate the pathophysiological role of the inflammatory JAK1/3 signaling pathway in diaphragm weakness in two distinct experimental models of critical illness. In the first experiment, mice received subcutaneous injections of PBS or C26 cancer cells and were fed chow formulated with or without the JAK1/3 inhibitor R548 for 26 days. Diaphragm specific force was significantly reduced in tumor-bearing mice receiving standard chow; however, treatment with the JAK1/3 inhibitor completely prevented diaphragm weakness. Diaphragm cross-sectional area was diminished by \u223c25% in tumor-bearing mice but was similar to healthy mice in tumor-bearing animals treated with R548. In the second study, mice received sham surgery or coronary artery ligation, leading to myocardial infarction (MI), and were treated with R548 or vehicle 1 h postsurgery, and once daily for 3 days. Diaphragm specific force was comparable between sham surgery/vehicle, sham surgery/R548 and MI/R548 groups, but significantly decreased in the MI/vehicle group. Markers of oxidative damage and activated caspase-3, mechanisms previously identified to reduce muscle contractility, were not elevated in diaphragm extracts. These experiments implicate JAK1/3 signaling in cancer- and MI-mediated diaphragm weakness in mice, and provide a compelling case for further investigation. Approximately one-third of critically ill patients develop respiratory failure, and the mortality rate of patients with respiratory failure is twice the rate of patients without respiratory failure but did not prevent gastrocnemius or soleus wasting (data not shown). JAK 1/3 inhibition also significantly reduced mRNA levels of the STAT3 downstream transcriptional target SOCS3, and the atrophy-related genes atrogin-1 and MuRF1 in TA muscle of cachectic mice (P < 0.05). Importantly, JAK 1/3 inhibition was well tolerated in tumor-bearing mice and did not exacerbate tumor growth or whole body cachexia. These data identify JAK 1/3 signaling as a key mediator of diaphragm muscle weakness during cancer cachexia in mice and establish inhibition of JAK 1/3 signaling as a promising therapeutic strategy worthy of additional investigation.In the first set of experiments, male CD2F1 mice received subcutaneous injections with either PBS or C26 colon carcinoma cells and were further subdivided into groups receiving either the JAK 1/3 inhibitor R548 or vehicle. R548 was formulated into chow (0.3 g R548/kg chow) and was provided to the animals upon PBS or C26 cell delivery, and throughout the study. The R548 dose was based on pharmacokinetic studies demonstrating that 0.3 g R548/kg chow maintained blood exposure levels above the levels associated with recovery of diaphragm muscle-specific force during mechanical ventilation , 14. Cho1) sham surgery/vehicle treatment, 2) sham surgery/R548 treatment, 3) myocardial infarction/vehicle (MI/vehicle), and 4) MI/R548. MI was initiated by ligation of the left anterior descending coronary artery, and the JAK 1/3 inhibitor was delivered 1 h post-MI (75 mg/kg body weight sc) and continued once daily for 3 days. Pharmacokinetic studies were conducted to determine the subcutaneous dose required to maintain plasma levels of the active drug above the efficacious level identified during mechanical ventilation (P < 0.05), and therapeutic administration of R548 completely prevented this loss leads to phosphorylation and activation of the intercellular JAKs and their downstream target STAT3 . ActivatIn conclusion, our findings highlight the important role of JAK 1/3 signaling in diaphragm muscle dysfunction in both cancer cachexia and acute MI in mice and provide a promising therapeutic target to preserve diaphragm function in these circumstances. These findings may have relevance to respiratory muscle dysfunction in critical illness in humans and warrant further study.I. J. Smith, G. L. Godinez, D. G. Payan, and T. M. Kinsella are employees and/or stockholders of Rigel Pharmaceuticals.Author contributions: I.J.S., D.G.P., T.M.K., A.R.J., and L.F.F. conception and design of research; I.J.S., B.R., A.B., G.L.G., A.R.J., and L.F.F. performed experiments; I.J.S., G.L.G., A.R.J., and L.F.F. analyzed data; I.J.S., T.M.K., A.R.J., and L.F.F. interpreted results of experiments; I.J.S., B.R., A.B., A.R.J., and L.F.F. prepared figures; I.J.S. drafted manuscript; I.J.S., D.G.P., T.M.K., A.R.J., and L.F.F. edited and revised manuscript; I.J.S., T.M.K., A.R.J., and L.F.F. approved final version of manuscript."} +{"text": "Ranunculus sieboldii, Mazus japonicus, Clinopodium confine and Plantago asiatica) on growth and Cd accumulation of Galinsoga parviflora in Cd-contaminated soil. In the pot experiment, mulching with M. japonicus straw increased the root biomass, stem biomass, leaf biomass, shoot biomass, plant height and activities of antioxidant enzymes of G. parviflora compared with the control, whereas mulching with straws of R. sieboldii, C. confine and P. asiatica decreased these parameters. Straws of the four Cd-tolerant plants increased the Cd content in roots of G. parviflora compared with the control. However, only straws of M. japonicus and P. asiatica increased the Cd content in shoots of G. parviflora, reduced the soil pH, and increased the soil exchangeable Cd concentration. Straw of M. japonicus increased the amount of Cd extraction in stems, leaves and shoots of G. parviflora by 21.11%, 29.43% and 24.22%, respectively, compared with the control, whereas straws of the other three Cd-tolerant plants decreased these parameters. In the field experiment, the M. japonicus straw also increased shoot biomass, Cd content in shoots, and amount of Cd extraction in shoots of G. parviflora compared with the control. Therefore, straw of M. japonicus can be used to improve the Cd extraction ability of G. parviflora from Cd-contaminated soil.Pot and field experiments were conducted to study the effects of mulching with straw of cadmium (Cd) tolerant plants ( This site was on the Ya'an campus of Sichuan Agricultural University Farm , Ya\u2019an City, Sichuan Province, China. The experimental field belongs to Sichuan Agricultural University, which is authorized by the government of Ya'an City. The field is not privately owned or protected. No specific permits were required for the described field studies. During the experiment, no other specific permissions were required because we conducted normal agricultural activities and no endangered or protected species were involved.The field study was conducted in an area where Ranunculus sieboldii, Clinopodium confine, Mazus japonicus and Plantago asiatica were collected from the Ya\u2019an campus farm of the Sichuan Agricultural University , China, at sites where the soil was not contaminated by heavy metals. The shoots were dried at 80\u00b0C to constant weight, then finely ground and sieved through a 5-mm-mesh nylon sieve. Galinsoga parviflora seedlings with two pairs of euphyllas were collected from the Ya\u2019an campus farm at a site not contaminated by heavy metals in September 2013.In August 2013, shoots of \u22121, total nitrogen (N) 3.05 g kg\u22121, total phosphorus (P) 0.31 g kg\u22121, total potassium (K) 15.22 g kg\u22121, alkali soluble N 165.30 mg kg\u22121, available P 5.87 mg kg\u22121, and available K 187.03 mg kg\u22121. The total Cd content was 0.101 mg kg\u22121 and the available Cd content was 0.021 mg kg\u22121. The basic soil properties and heavy metal concentrations were determined according to Bao (2000) Inceptisol soil samples (purple soil in the Genetic Soil Classification of China) were collected from the Ya\u2019an campus farm in August 2013. The basic chemical properties of the soil were pH 7.02, organic matter 41.38 g kg2\u00b72.5 H2O at 10 mg kg\u22121G. parviflora were transplanted into each pot, and 6 g shoots \u22122). Five treatments were applied: not mulched with straw (control), mulched with R. sieboldii straw, mulched with C. confine straw, mulched with M. japonicus straw, and mulched with P. asiatica straw. Each treatment was repeated three times with a completely randomized design with 10-cm spacing between pots. The soil moisture was maintained at 80% of field capacity from when the G. parviflora plants were transplanted until the plants were harvested.The experiment was conducted at the Ya\u2019an campus farm in August\u2013October 2013. The soil samples were air-dried and passed through a 5-mm sieve in August 2013, and then 4.0 kg of the air-dried soil was weighed into each polyethylene pot . Cadmium was added to the soil samples as CdClG. parviflora plants was measured, and the uppermost young leaves of 2 cm in length were collected to determine the activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) \u22121 HCl for 10 min to remove Cd adhering to the root surface. The roots, stems, and leaves were further washed with deionized water and dried at 80\u00b0C to constant weight for dry weight and Cd content determination. The dried plant samples were finely ground and sieved through a 0.149-mm-mesh nylon sieve for chemical analysis. Samples (0.5 g) were digested in HNO3/HClO4 , and then the volume was diluted to 50 ml with deionized water. The Cd concentrations in roots, stems, and leaves were determined using an iCAP 6300 ICP spectrometer \u22121 DTPA-TEA and analyzed with an iCAP 6300 ICP spectrometer At maturity (after 50 d), the height of the \u22121, total N 1.14 g kg\u22121, total P 0.66 g kg\u22121, total K 21.54 g kg\u22121, alkali solution N 78.55 mg kg\u22121, available P 33.67 mg kg\u22121, available K 111.07 mg kg\u22121, and total Cd 1.80 mg kg\u22121. The basic soil properties and heavy metal concentrations were determined according to Bao (2000) 2 (1.0 m\u00d71.0 m). Seedlings of G. parviflora were planted directly in the soil at a density of 100 plants m\u22122 (in a 10 cm\u00d710 cm grid) in February 2014. Shoots of the four Cd-tolerant species were applied as mulches (density 225 g m\u22122) on the soil surface in each plot. The five treatments in the experiment were identical to those of the pot experiment. Each treatment was repeated three times (three plots). The cultivation and management of G. parviflora seedlings were as previously described for the pot experiment. At maturity (after 50 d), the G. parviflora shoots were harvested to determine shoot biomass and Cd content as described for the pot experiment.The field experiment was conducted at the Ya\u2019an campus farm in February\u2013March 2014. Inceptisol soil samples were collected from the Cd-contaminated area of the farm. The basic chemical properties of the soil were as follows: pH 6.96, organic matter 34.33 g kgStatistical analyses were performed using SPSS 13.0 statistical software . Data were analyzed by one-way ANOVA with least significant difference (LSD) at the 5% confidence level.The following ratios were calculated: root/shoot ratio\u200a=\u200aroot biomass/shoot biomass M. japonicus straw mulch significantly (P<0.05) increased the root, stem, leaf, and shoot biomasses of G. parviflora by 18.75%, 9.35%, 33.33%, and 16.11%, respectively, compared with those of the control, whereas mulching with R. sieboldii, C. confine, and P. asiatica straws decreased these biomasses compared with the control , whereas R. sieboldii, C. confine, and P. asiatica straws decreased the plant height by 15.23% (P<0.05), 14.66% (P<0.05), and 14.94% (P<0.05), respectively, compared with the control , 9.42% (P<0.05), and 6.68% (P<0.05), respectively, compared with the control, whereas R. sieboldii, C. confine, and P. asiatica straws decreased activities of these enzymes and 4.64% (P>0.05), respectively, compared with that of the control, whereas the straws of R. sieboldii and C. confine decreased the stem Cd content. The treatments affected Cd content in leaves of G. parviflora in the rank order P. asiatica straw > R. sieboldii straw > C. confine straw > M. japonicus straw > control. The treatments had a similar effect on Cd content in shoots of G. parviflora to that on stem Cd content. The straws of M. japonicus and P. asiatica increased shoot Cd content by 8.34% (P<0.05) and 13.67% (P<0.05), respectively, compared with the control. The shoot BCF of G. parviflora was enhanced by the straws of M. japonicus and P. asiatica, but was decreased by the straws of R. sieboldii and C. confine, compared with the control and 16.68% (P<0.05), respectively, compared with that of the control, whereas the R. sieboldii and C. confine straws decreased root Cd extraction , 29.43% (P<0.05), and 24.22% (P<0.05), respectively, compared with the control, whereas the other three straw types decreased Cd extraction in these organs compared with that of the control, whereas straws of M. japonicus (P>0.05) and P. asiatica (P<0.05) decreased soil pH in the pot experiment (C. confine straw > R. sieboldii straw > control > M. japonicus straw >P. asiatica straw. The effects on soil exchangeable Cd concentration were ranked as P. asiatica straw > M. japonicus straw > control > R. sieboldii straw > C. confine straw in the pot experiment (R. sieboldii and C. confine decreased the soil exchangeable Cd concentration by 0.27% (P>0.05) and 1.37% (P<0.05), respectively, whereas the straws of M. japonicus and P. asiatica increased soil exchangeable Cd concentration by 1.09% (P<0.05) and 1.50% (P<0.05), respectively, compared with that of the control.The straws of periment . The treperiment . The strM. japonicus straw increased the shoot biomass of G. parviflora compared with that of the control (P<0.05), whereas the other three treatments decreased the shoot biomass , but was decreased by the other three treatments (In the field experiment, biomass , which weatments .M. japonicus straw increased the root, stem, leaf, and shoot biomasses of G. parviflora compared with those of the control, whereas the straws of R. sieboldii, C. confine, and P. asiatica decreased these biomasses. An identical effect on shoot biomass of G. parviflora was observed in the field experiment. There might be two reasons for this phenomenon. First, the promotive effect of nutrients from M. japonica straw on growth of G. parviflora exceeded the inhibitory effect of organic acids from M. japonica straw, whereas the promotive effect of nutrients from R. sieboldii, C. confine, and P. asiatica straws on growth of G. parviflora was weaker than the inhibitory effect of organic acids from these straws. Second, allelochemicals from M. japonica straw might promote growth of G. parviflora, whereas allelochemicals from R. sieboldii, C. confine, and P. asiatica straws might inhibit growth of G. parviflora. Ultimately, in the pot experiment, M. japonicus straw enhanced, whereas R. sieboldii, C. confine, and P. asiatica straws decreased the plant height of G. parviflora compared with that of the control.Plant straw contains many nutrients and allelochemicals, which are released during the process of straw decay and decomposition and can be absorbed by living plants \u22122\u00b7 in their organs, leading to cellular peroxide poisoning and damage, which inhibits plant growth and reduces plant biomass M. japonicus enhanced SOD, POD, and CAT activities of G. parviflora compared with that of the control, whereas the straws of R. sieboldii, C. confine, and P. asiatica reduced activities of these enzymes. This finding might be related to allelochemicals from M. japonica straw, which could enhance the tolerance of G. parviflora to Cd stress, whereas allelochemicals from R. sieboldii, C. confine, and P. asiatica straws might reduce the Cd stress tolerance of G. parviflora.Under stress conditions, plants produce OR. sieboldii and C. confine, but decreased by the straws of M. japonicus and P. asiatica compared with that of the control. It may be that allelochemicals from R. sieboldii and C. confine straws promote the secretion of organic acids from the roots of G. parviflora during plant growth. In addition, in the pot experiment, the soil exchangeable Cd concentration was decreased by the straws of R. sieboldii and C. confine, and increased by the straws of M. japonicus and P. asiatica.Under heavy metal contamination of the soil, studies on the effects of heavy metal absorption by plants have focused mainly on the rhizosphere environment R. sieboldii, C. confine, M. japonicus, and P. asiatica increased the Cd content in roots of G. parviflora compared with that of the control in the pot experiment, but only the straws of M. japonicus and P. asiatica increased the Cd content in shoots of G. parviflora in both the pot and field experiments. This result indicates that the organic acids and other organic matter derived from the straw by decay and decomposition can lead to increased Cd content in roots of G. parviflora, and only allelochemicals from M. japonica straw may increase the Cd content in shoots of G. parviflora. Thus, allelochemicals from different plant species may play different roles in Cd absorption and translocation by G. parviflora. The straws of M. japonicus and P. asiatica increased, whereas R. sieboldii and C. confine straws decreased, the amount of Cd extraction in roots of G. parviflora in the pot experiment compared with the control. Only M. japonicus straw increased the amount of Cd extraction in stems, leaves and shoots of G. parviflora compared with those of the control, whereas the other three straw types decreased Cd extraction in these organs, in both the pot and field experiments. Thus, the present results showed that the straw of M. japonicus can improve the phytoremediation ability of G. parviflora and can be used to improve the Cd extraction ability of G. parviflora from Cd-contaminated soil.The straws of"} +{"text": "Health Psychology and Behavioral Medicine, 2(1), 296\u2013313. http://dx.doi.org/10.1080/21642850.2014.892429Paulsson Do, U., Edlund, B., Stenhammar, C., & Westerling, R. (2014). Vulnerability to unhealthy behaviours across different age groups in Swedish Adolescents: a cross-sectional study. When the above article was first published online, the following Acknowledgement Section was omitted in error. This has now been amended in the online version of this article."} +{"text": "AedesMeigen (Diptera: Culicidae) mosquito species populations in the western region of Saudi Arabia, especially in and around Jeddah, are increasing, therefore increasing susceptibility of humans to the dengue virus. An extensive survey was carried out for one year, and four species were identified with the help of different pictorial keys available. The identification was based on morphological characteristics of adult femaleAedesmosquitoes.The AedesMeigen (Diptera: Culicidae) species are becoming the most important from a medical point of view all over the world.Aedesspecies are vectors of arbo-viruses that infect various vertebrates, including humans. The most common arbo- viruses spread byAedesspecies and infecting humans are the dengue fever virus, yellow fever virus, and chikungunya virus. TheAedesspecies of Saudi Arabia have been studied by several people, such asSeveral mosquito species are of medical importance, butAedes aegypti, Aedes arabiensisandAedes caspius.Aedesspecies from this region.Aedes caspiusfrom the eastern part of the country.Aedes caspius, from the southwestern region, excluding Jeddah. Al Zaharani (2001) reported onlyAedes vittatusfrom the southern region.Aedes vexans arabiensis, Aedes vittatus, Aedes caspiusandAedes caballus. Godsy Jr.et al. (2003) reportedAedes unilineatusfrom Makkah region. Al Kherji (2005) only collectedAedes caspiusfrom Riyadh. Azzam (2006),Aedes caspiusandAedes aegyptifrom Jeddah.Aedesmosquito fauna in the western region of Saudi Arabia. In an effort to better understand the fauna, we performed a comprehensive study of the aedine mosquitoes of the western region. The present work is the result of intensive surveillance for almost one year, from January 2010 to December 2010. The study revealed the presence of four species ofAedesin this region. Some of them have been reported in earlier studies from different parts of Saudi Arabia.There is no authentic record ofAedesspecies bite during the day and sometimes early night, and dawn and dusk are the peak biting times (WHO 2008). A thorough sampling was carried out by installing the light traps in various habitats in the western region of the country. Black Hole light traps were used to attract the adult mosquitoes during the entire period of surveillance. Powered aspira- tors and flash torches were also used to collect mosquitoes from their different resting places.Aedesspecies, which were sorted out species wise and sex wise to determine the male:female ratio. Identification was done on the basis of adult female morphological characters with the help of different standard taxonomic keys and catalogues aegypti(L.) was most commonly collected from almost all the locations of Jeddah and other towns.Aedes (Ochlerotatus) caspius was restricted in the regions that are close to sea. The highest number ofAedes (Ochlerotatus) caspiuswere collected from Bariman and South of Jeddah, and a few specimens were also collected from Rabiq and Al Qooz.Aedes (Ochlerotatus) vexansvar.arabiensis(Meigen) was mainly concentrated in Al-Qunfudha and Al-Qooz, but a few specimens were also collected from Jeddah and other areas.Aedes vittatusBigot was abundantly found in Al- Qooz and Al-Qunfudha. From the city of Jeddah, two female specimens ofAe. vittatuswere collected from Um-Salam region only , followed byAedes vexans(28.576%),Ae. vittatus(11.90%), andAe. caspius(2.477%).Aedes vittatusandAe. vexans arabiensishave not been reported previously from Jeddah city..The most abundant species recorded in the western region wasAedesmosquitoes is necessary for effective control of Dengue fever and other arbo-viral diseases prevalent in this region. A simple guide with the diagnostic features is prepared to identify theAedesmosquitoes of Western region of Saudi Arabia.Correct identification of1. Silvery white scales on the head, especially on the vertex.2. Clypeus with white silvery scales.3. Palpi silvery white at tips.4. Scutum with lyre-shaped silvery scale ornamentation.5. Mid-femur with white longitudinal stripe from base to tip.6. Hind tarsi with conspicuous white basal rings on 1\u20134 segments.7. 5th segment of hind tarsi entirely white.1. White upright scales on the vertex.2. Clypeus pale brown.3. Palpi with light and dark scales.4. Proboscis dark at the tip but light in the middle and at the base.5. Scutum golden or fawn colored scales with narrow dorsocentral stripes of white scales.6. Tarsomeres with rings of pale scales.7. Hind tarsomeres with both basal and apical pale rings.8. Wings with white and dark scales. Base of costa mostly dark scales, vein 'R' with dark and pale white scales.9. Abdominal terga with median pale stripes, sometimes entirely pale scales.1. Vertex with yellowish scales.2. Palpi brown with pale scales at tips.3. Plurae with many white or creamy scales.4. Wings with dark scales.5. Tarsi speckled with narrow basal pale rings.1. Silvery white scales on the narrow vertex.2. Clypeus with white silvery scales.3. Palpi with silvery white tips.4. Wings with mainly narrow scales on all veins.5. Scutum with three pairs of small round silvery white spots.6. Tibiae are dark in color each with white spots and white sub basal white band.7. Tarsomeres 1\u20134 with white bands; fifth tarsomere is fully white.aegypti- Clypeus without scales (exceptA. vit-tatus), scutum with other mark- mark- ings......................................................21. Clypeus with white scales, mid femur with an anterior white stripe from base to tip; scutum with lyre-shaped silvery scale\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026...vittatus- Otherwise marked\u2026\u2026\u2026\u2026\u2026\u2026.......32. Scutum with three pairs of small, round, white spots; each femora with preapical white ring. Tibiae dark in color, each with white subbasal band...........................................caspius- Scutum with out darso-central white stripes..................................................43. Scutum with golden or fawn color scales with narrow darso-central stripes of white scales. Hind tarsomeres with both basal and apical rings, fifth hind tarsal segment pale, wings with white and dark scales.........................................vaxansvr.arabiensis4. Hind tarsi with pale rings confind to bases of segments, fifth hind tarsal segment wholly dark. Abdominal terga without median pale stripes.................."} +{"text": "AbstractCissusfrutescens and Cissusarborea have a long history of confusion. Cissusfrutescens Blanco belongs to the genus Melicope (Rutaceae) and we herein correct a nomenclatural mistake made by T.G. Hartley in the revision of Melicope. The name Melicopeconfusa (Merr.) P.S. Liu was accepted for this taxon by Hartley. However, Cissusfrutescens Blanco represents the earliest name for this entity and a new combination, Melicopefrutescens (Blanco) Appelhans & J.Wen is herein proposed. Neotypification of Cissusarborea Blanco is also provided.The names Cissusfrutescens Blanco was published in 1837 in the first edition of Francisco Manuel Blanco\u2019s Flora de Filipinas Benth. [Evodia =EuodiaRutaceae] . Euodiaroxburghiana is currently known as Melicopelunu-ankenda (Gaertn.) T.G.Hartley, and interestingly, only a single specimen of this widespread species was cited from the Philippines in the latest revision of Melicope and Euodia , suggesting that it might be rare in the Philippines. This was highlighted by Merrill, who stated that the species was \u201cnot definitely known from the Philippines\u201d was lost and therefore he chose Borden 3045 (NY) among the paratypes, as its lectotype. He also designated Merrill 904 as the neotype of Cissusfrutescens, which he placed as a synonym of Melicopeconfusa Mez. (Cissusarborea (L.) Des Moul. is a synonym of Nekemiasarborea (L.) J.Wen & Boggan Mez. ; and Cis& Boggan , so the Taxon classificationPlantaeSapindalesRutaceae(Blanco) Appelhans & J.Wencomb. nov.urn:lsid:ipni.org:names:77151881-1Cissusfrutescens Blanco, Flora de Filipinas, ed. 1: 70. 1837. Type: Philippines. Luzon: Rizal, Mar 1915, Merrill: Species Blancoanae No. 904 .Cissusarborea Blanco, nom. illeg., Flora de Filipinas, ed. 2: 51. 1845 . Type: Philippines. Luzon: Rizal, Mar 1915, Merrill: Species Blancoanae No. 904 .Euodiaconfusa Merr., Philipp. J. Sci. 20: 391. 1922. Melicopeconfusa (Merr.) P.S. Liu, III. Native Introd. Lign. Pl. Taiwan 2: 876. 1962. Type: Philippines. Luzon: Bataan, FB 3045Borden .Melicopefrutescens is known to occur in Borneo, Sulawesi and the Moluccas. It typically grows in the lowlands but reached elevations of up to 1800 m in the Philippines. The species occurs in primary, secondary, and disturbed rainforests.In addition to its distribution in the Philippines,"} +{"text": "The Thai-Myanmar border is a remaining hotspot for malaria transmission. Malaria transmission in this region continues year-round, with a major peak season in July-August, and a minor peak in October-November. Malaria elimination requires better knowledge of the mosquito community structure, dynamics and vectorial status to support effective vector control.Anopheles mosquitoes were collected using CDC light traps and cow bait in 7 villages along the Thai-Myanmar border in January 2011 - March 2013. Mosquitoes were determined to species by morphological characters. Plasmodium-positivity was determined by circumsporozoite protein ELISA.Adult Anopheles mosquitoes collected were assigned to 26 species, with Anopheles minimus sensu lato (s.l.) (40.32\u00a0%), An. maculatus s.l. (21.43\u00a0%), An. annularis s.l. (14.43\u00a0%), An. kochi (5.39\u00a0%), An. tessellatus (5.26\u00a0%), and An. barbirostris s.l. (3.52\u00a0%) being the top six most abundant species. Plasmodium-infected mosquitoes were found in 22 positive samples from 2906 pooled samples of abdomens and heads/thoraxes. Four mosquito species were found infected with Plasmodium: An. minimus s.l., An. maculatus s.l., An. annularis s.l. and An. barbirostris s.l. The infectivity rates of these mosquitoes were 0.76, 0.37, 0.72, and 1.74\u00a0%, respectively. Consistent with a change in malaria epidemiology to the predominance of P. vivax in this area, 20 of the 22 infected mosquito samples were P. vivax-positive. The four potential vector species all displayed apparent seasonality in relative abundance. While An. minimus s.l. was collected through the entire year, its abundance peaked in the season immediately after the wet season. In comparison, An. maculatus s.l. numbers showed a major peak during the wet season. The two potential vector species, An. annularis s.l. and An. barbirostris s.l., both showed peak abundance during the transition from wet to dry season. Moreover, An. minimus s.l. was more abundant in indoor collections, whereas An. annularis s.l. and An. barbirostris s.l. were more abundant in outdoor collections, suggesting their potential role in outdoor malaria transmission.The 2986 An. minimus s.l. and An. maculatus s.l. and identified An. annularis s.l. and An. barbirostris s.l. as additional vectors with potential importance in malaria transmission after the wet season.This survey confirmed the major vector status of Plasmodium vivax, a parasite more resistant to control measures and this species was collected only in the wet season with a peak density occurring in August and September.Mosquito collection was done in three roughly divided seasons based on rainfall and the temperature variation: hot, wet and dry. All major ity Fig.\u00a0. An. miner) Fig.\u00a0. It alsoer) Fig.\u00a0. In compons Fig.\u00a0. This spAnopheles mosquitoes were also illustrated by the cumulative abundance of major species, when the three seasons were compared . The mean number of An. maculatus s.l. collected per season was significantly different between the three seasons . Except for An. minimus s.l. which was prevalent in all seasons, the other three species were scarce in the hot season. During the wet season, indoor collection was more efficient than outdoor collection for all four species. This was particularly true of An. maculatus s.l., the dominant species collected with indoor traps and co-dominant with An. minimus s.l. (n\u2009=\u2009108). Plasmodium infections were both detected in these two species, pointing to their roles in malaria transmission during the wet-dry season transition.To explore the potential vectorial status of the In addition, all four mosquito species were found malaria parasite positive during the minor peak of malaria incidence, suggesting that they all might be involved in malaria transmission.Effective vector control as an integrative component of malaria control relies heavily on our understanding of the community structure, seasonal abundance, and infection status of the vector species. Anthropogenic land use activities and insecticide-based control measures have resulted in major shifts of mosquito species abundance and changes in biting behavior, which require continued monitoring of vectors . In thisAnopheles species from a collection of ~3000 adult Anopheles mosquitoes. An. minimus s.l., An. maculatus s.l. and An. annularis s.l. are the top three most abundant species, making up more than 75\u00a0% of all Anopheles species. This finding further supports An. minimus s.l. and An. maculatus s.l. as the most important malaria vectors in this area [An. minimus s.l. as the principal vector in Tak Province is reflected in its absolute abundance (>40\u00a0%), which is consistent with observations made 10\u00a0years ago [P. vivax CS proteins in both species further demonstrated their competence in transmitting P. vivax malaria. In contrast, another important vector An. dirus s.l., a forest fringe mosquito, was relatively rare, which is likely due to deforestation.Our survey identified 26 his area , 12. Theears ago . The detAn. annularis s.l. as a potentially important malaria vector. Normally, An. annularis s.l. is considered as zoophagic and predominates in rice fields [P. vivax infections in Indonesia [An. annularis s.l. in western Thailand, resulting in increased abundance of this species (>14\u00a0%) [P. falciparum and P. vivax CS proteins in this species demonstrated its competence in transmitting both parasite species. Moreover, its high density in outdoor traps indicates its potential role in outdoor transmission in the late wet to dry season in this area.This study identified e fields . It was ndonesia . In Balindonesia . Climatispecies >4\u00a0% [1, 1 (>14\u00a0%) , 16. TheAnopheles barbirostris s.l. was recognized as a potential vector for P. falciparum in Bangladesh and Sri Lanka [An. campestris-like mosquitoes were found to be experimentally susceptible to P. vivax infection, only one previous report found naturally-caught An. barbirostris s.l. to be P. vivax positive in Thailand [An. barbirostris s.l. as a relatively abundant species throughout the seasons in both indoor and outdoor collections. Its anthropophilic behavior and PV210 positivity further suggest it as an increasingly important vector for, at least, P. vivax. The abundance of newly identified vectors for P. vivax, such as An. barbirostris s.l., and fewer numbers of other major vectors for malaria in the region, such as An. dirus s.l., may contribute to the shift of the prevalence ratio of P. vivax/P. falciparum in this area.The Barbirostris group is considered a suspected vector of malaria and filariasis in Thailand , 17, 18.ri Lanka , 20. WheThailand . This stAn. minimus s.l. was most abundant during the transition from wet to dry season. In addition, this mosquito species was more abundant in indoor than outdoor collections. In comparison, An. maculatus s.l. was the most abundant species in the wet season in both indoor and outdoor collections, consistent with a previous study [Plasmodium-positivity in this mosquito highlights its role in malaria transmission during the wet season. An. annularis s.l. was detected at a similar season as An. minimus s.l., suggesting its importance in malaria transmission immediately after the wet season. Further information on each vector\u2019s susceptibility to malaria parasites and their seasonality would be useful for vector control intervention planning which is an important tool to support malaria elimination in the region.Most mosquito species in our study were found seasonally. us study . FurtherPlasmodium positivity, and the seasonal dynamics of malaria incidence in the study area are compatible. The region\u2019s apparent transition to P. vivax predominance in malaria incidence is also reflected in our detection of mostly P. vivax CS proteins in infected vectors. Based on the picture presented in Fig.\u00a0An. minimus s.l., which is subsequently replaced by An. maculatus s.l. in the wet season. After the wet season, the second peak of malaria incidence is likely transmitted by a mixture of competent vector species that prefer either indoor (An. minimus s.l.) or outdoor biting (An. annularis s.l. and An. barbirostris s.l.). While this survey confirmed the major vector status of An. minimus s.l. and An. maculatus s.l., it revealed two additional species, An. annularis s.l. and An. barbirostris s.l., as potential vectors after the rainy season. This complex vectorial system of malaria transmission, including seasonality and preferences for either indoor or outdoor feeding, needs to be taken into account when planning for malaria elimination in this region.The overall seasonal fluctuation of potential vectors, their An. minimus s.l. and An. maculatus s.l. still are the major malaria vectors in the northwestern Thailand. We also identified An. annularis s.l. and An. barbirostris s.l. as additional vectors which may be important for outdoor malaria transmission after the wet season. The current information can be used to guide vector control program which is an essential tool to support malaria elimination in the region.The present study has confirmed that"} +{"text": "P. angelicae group from China was studied, and six new species are described: P. hanmiensis, n. sp., P. nanlingensis, n. sp., P. reduncicauda, n. sp., P. spargocerca, n. sp., P. subincana, n. sp., and P. varimargina, n. sp. A key to the identification of males of the 40 Chinese species is given.The Phaonia (Diptera: Muscidae), with P. viarum as the type species. The genus and species from the Palaearctic Region were first divided into 16 groups established 6 groups , then 186 groups , and lat6 groups . Followia et al. divided Ringdahl and diviRingdahl . Now theause Xue revised The type specimens of six new species are all deposited at the Institute of Entomology, Shenyang Normal University, Shenyang, China.ors, orbital setae; fr, frontal setae; prst acr, presutural acrostichal setae; acr, acrostichal setae; prst dc, presutural dorsocentral setae; dc, dorsocentral setae; post dc, postsutural dorsocentral setae; ial, intraalar setae; pra, prealar setae; av, anteroventral setae; a, anterior seta; ad, anterodorsal setae; pd, posterodorsal setae; p, posterior setae; pv, posteroventral setae; v, ventral setae; r-m, radio-medial cross-vein; dm-cu, medio-cubital cross-vein; 4+5R, branch of radius; and M, medial vein. Other abbreviations used are: collect., collector; loc., locality; and IESNU, Institute of Entomology, Shenyang Normal University, China.The morphological terminology follows that of McAlpine (1981). Absolute measurements are used for the body length in millimeters (mm). The following abbreviations are used for characters: -- Epistoma situated in front of the anterior margin of frons or at the same vertical line in profile; thorax without presutural acr; basisternum of prosternum bare; mid tibia with p and pv; abdomen black; distal part of cerci with inboard processus and outboard processus.Diagnosis. P. angelicae group are mainly distributed in Sichuan Province, China.Distribution. -- The 40 Chinese species of Bionomics. -- Relevant records are lacking.1. Fore tibia dense with long, brush-like hairs on the ventral surface2\u2014 Fore tibia without above mentioned hairs on the ventral surface72. Prementum about 6.0 times as long as Broad3\u2014 Prementum about 4.0 times as long as Broad4pv3. Basal part of wing and haltere blackish brown; hind femur without P. kunjirapensisXue pv in basal half\u2014 Basal part of wing light brown and haltere yellow; hind femur with short P. paederocercaFeng ad; hind femur without pv; outboard processus of cercus broad and big4. Mid tibia with 1\u20132 P. biastostylaXue, 1998ad\u2014 Mid tibia without 55. Scape yellow, pedicel black, postpedicel blackish brownP. subhybridaFeng \u2014 Antenna black6pd6. Gena about 1/3 of eye in height; hind tibia with 1 sub-basal P. labidocercaFeng pd\u2014 Gena about 1/2 of eye in height; hind tibia without additional P. mengiFeng, 2000post dc7. Scutum with 3 P. longirostrisXue post dc\u2014 Scutum with 4 8pd8. Hind tibia without additional 9pd in sub-basal\u2014 Hind tibia with 1\u20133 short and weak 249. Tibiae yellow or reddish brown, sometimes basal parts black10\u2014 Tibiae black, sometimes basal parts reddish Brown12pv; each tergite with median black vita10. Parafacial slightly wider than the postpedicel; the anterior margin of gena with 2 rows of upcurved subvibrissal setulae; mid tibia with 1 P. sunwuensisXue pv; each tergite without median black vita\u2014 Parafacial narrower than the postpedicel; the anterior margin of gena without above mentioned setulae; mid tibia with 2\u20133 11fr row, extending to both sides of anterior ocellus, lower 2/5 strong and long; tibiae yellow; hind tibia with 3 av, 2 ad11. Frons with P. subemarginataFang, Li fr in lower half; tibiae black in basal, yellow in apical; hind tibia with 2 av, 1 ad\u2014 Frons only with 5 pairs of P. daxiongiFeng, 2001ad12. Mid tibia with 1\u20132 13ad\u2014 Mid tibia without 1513. Katepimeron bareP. incana , Jilin Province; Benxi City, Liaoning Province.P. curvicercalis2. Distribution. -- China: Pan County (type loc.), Guizhou Province.P. daxiongi3. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. fusciantenna4. Distribution. -- China: Mt. Zhougong (type loc.), Yaan City, Sichuan Province.P. fuscitibia5. Distribution. -- Japan: Sapporo (type loc.). China: Jiagedaqi, Heilongjiang Province; Mt. Changbai, Jilin Province. Mongolia. Russia.P. hamiloba Ma, 1992: 4436. Distribution. -- China: Yushu County (type loc.), Qinghai Province; Kangding County, Sichuan Province; Mt. Houding, Zhangjiakou City, Hebei Province.P. hanmiensis Xue et Zhang, n. sp. ; mid tibia with 2 p, 2 pv, without ad; hind femur with av in the apical half, without pv; hind tibia with 3\u20134 av, 2 ad, 1 pd in apical quarter, without additional sub-basal pd and apical pv; all tarsi longer than tibiae; claws and pulvilli short and small.Abdomen. Black in ground color, nearly rounded in dorsal view, covered with gray pruinosity; tergites 4 and 5 slightly shiny, each tergite with median narrow black vitta, without shining patches; sternite 1 bare, the posterior part of every sternite 2\u20135 with a pair of long setae; cercus with many thin hairs on inner margin, with inconspicuous inboard processus.Female. -- Unknown.HolotypeType material. -- . China, Tibet, Motuo County, Hanmi, 2150-3200 m a.s.l., 9 August 2003, Mingfu Wang Collect., \u2642 (IESNU). Paratype. Same data as holotype. \u2642 (IESNU).Remarks. -- This new species is similar to P. zhougongshana Ma etpra long and strong, about 1.5 times as long as posterior notopleural seta; katepimeron with hairs; legs all black; hind tibia with 2 ad; cersus with many thin hairs on inner margin, without distinct inboard processus.Etymology. \u2014 The species name is based on the place of collection, Hanmi.Distribution. -- China: Tibet.P. hunyuanensis Ma et Wang, 1998: 12218. Distribution. -- China: Hunyuan County (type loc.), Shanxi Province.P. incana (9. . incana : 81Distribution. -- Germany: Kiel (type loc.). China: Mt. Changbai, Jilin Province; Haiyan County, Maqin County, Qinghai Province. Mongolia. Russia.P. jiagedaqiensis Ma et Cui, 1992: 92410. Distribution. -- China: Jiagedaqi (type loc.), Heilongjiang Province.P. kunjirapensis11. Distribution. -- China: Kunjirap (type loc.), Tashikuergantajike Autonomous County, Xinjiang Uygur Autonomous Region.P. labidocerca12. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. latimargina13. Distribution. -- China: Mt. Galongla (type loc.), Motuo County, Tibet.P. longipalpis14. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. longirostris15. Distribution. -- China: Mt. Xiaowutai (type loc.), Hebei Province.P. maowenensis16. Distribution. -- China: Sanlong (type loc.), Maowen County, Sichuan Province.P. megacerca17. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. megistogenysa18. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. mengi19. Distribution. -- China: Mt. Jiaoding (type loc.), Hanyuan County, Sichuan Province.P. mimoincana20. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. nanlingensis Xue et Zhang, n. sp. . Paratype. Same data as holotype. 5 \u2642\u2642 (IESNU).Remarks. -- This new species is similar to P. zhougongshana Ma etav, without a, p; surstylus slender, but distal part enlarged.Etymology. \u2014 The species name is based on the place of collection, Nanling, where Mount Xiaohuangshan lies.Distribution. -- China: Guangdong Province.P. nigeritegula22. Distribution. -- China: Taiziping (type loc.), Mt. Emei, Sichuan Province.P. ningxiaensis Ma et Zhao, 1992: 92423. Distribution. -- China: Xixia (type loc.), Jingyuan County, Ningxia Hui Autonomous Region.P. paederocerca24. Distribution. -- China: Wanfoding (type loc.), Mt. Emei, Sichuan Province; Mt. Jiaoding, Hanyuan County, Sichuan Province.P. paomashanica25. Distribution. -- China: Mt. Paoma (type loc.), Kangding County, Sichuan Province.P. papillaria26. Distribution. -- China: Qingtiange (type loc.), Weixi Lisu Autonomous County, Yunnan Province.P. planeta27. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. reduncicauda Xue et Zhang, n. sp. . Paratype. Same data as holotype. 2 \u2640\u2640 (IESNU).Remarks. -- This new species is similar to P. mimoincanapv row, which was stronger in the basal half; posterior margin of tergite 3 and 4 with stripes; tergite 5 with a pair of shining lateral patches.Etymology. -- The species name is derived from the Latin words \u201creduncus\u201d meaning curved backward and \u201ccauda\u201d meaning tail, referring to the inner processus of the cersus being curved backward.Distribution. --China: Tibet.P. scrofigena Ma et29. Distribution. -- China: Barkam County (type loc.), Sichuan Province.P. spargocerca Xue et Zhang, n. sp. . Paratype. Same data as holotype, \u2640 (IESNU).Remarks. -- This new species is similar to P. wanfodingapra slightly longer than or subequal to posterior notopleural seta; anterior spiracle light yellow to white.Etymology. -- The species name is derived from the Greek words \u201cspargosis\u201d meaning enlarged and \u201ccercus\u201d meaning cercus, referring to male cerci being broad in the apical part.Distribution. -- China: Yunnan Province.P. subconsobrina Ma, 1992: 92331. Distribution. -- China: Mt. Changbai (type loc.), Jilin Province.P. subemarginata32. Distribution. -- China: Mt. Emei (type loc.), Sichuan Province.P. subhybrida33. Distribution. -- China: Mt. Erlang (type loc.), Yaan City, Sichuan Province.P. subincana Xue et Zhang, n. sp. . Paratype. Same data as holotype. 2 \u2642\u2642 (IESNU).Remarks. -- This new species is similar to P. mimoincanaad; hind femur without pv; hind tibia with 1 short and weak pd in the middle; cerci nearly quadrate in the posterior view, outboard processus broad, and longer than the inboard processus.Etymology. -- The species name is based on the new species being similar to P. mimoincanaDistribution. -- China: Tibet.P. sunwuensis35. Distribution. -- China: Heilongjiang Province (type loc.).P. varimargina Xue et Zhang, n. sp. . Paratype. Same data as holotype. 2 \u2642\u2642 (IESNU).Remarks. -- This new species is similar to P. latimarginapv that are long and strong in the basal twothirds; mid tibia with 3\u20134 p, 1 pv; hind femur without pv in the basal half; hind tibia with 3 ad; abdomen nearly rounded in dorsal view.Etymology. -- The species name is derived from the Latin words \u201cvariatus,\u201d meaning shifting and \u201cmarginis,\u201d meaning margin, referring to the posterior margins of tergites 3\u20135 having broad shifting stripes.Distribution. -- China: Tibet.P. wanfodinga37. Distribution. -- China: Wanfoding (type loc.), Mt. Emei, Sichuan Province; Mt. Erlang, Yaan City, Sichuan Province.P. wulinga38. Distribution. -- China: Mt. Leigong (type loc.), Leishan County, Guizhou Province.P. zhangyeensis Ma et Wu, 1992: 92439. Distribution. -- China: Zhangye City (type loc.), Gansu Province.P. zhougongshana Ma et40. Distribution. -- China: Mt. Zhougong (type loc.), Yaan City, Sichuan Province."} +{"text": "Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A.\u00a0thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes. \u2022Arabidopsis thaliana are presentedThe genomes of 1,135 naturally inbred lines of \u2022Relict populations that continue to inhabit ancestral habitats were discovered\u2022The last glacial maximum was important in structuring the distribution of relicts\u2022This collection will connect genotypes and phenotypes on a species-wide level Arabidopsis thaliana reveals its global population structure, migration patterns, and evolutionary history and provides a rich genetic resource for studying phenotypic variation and adaptation.Genomic sequencing analysis of over 1,000 natural inbred lines of Arabidopsis thaliana remains at the forefront of modern genetics. Decades of work have not only established much of what we know about the physiology and development of plants but also provided insight into how wild populations adapt to biotic and abiotic environments. Few systems share the key advantage of A.\u00a0thaliana for GWAS or complementary forward genetics approaches: the ready availability of a large collection of naturally inbred lines (accessions) that are products of natural selection under diverse ecological conditions. This makes it possible to link genotypes and phenotypes to fitness effects in the laboratory and the field , we retained sequences of 413\u00a0RegMap and 722 new lines, for a total of 1,135 accessions with whole-genome information (see the Data Release section). These 1,135 lines are the focus of this paper; the imputed RegMap set will be described in another paper. Together, the RegMap and 1001 Genomes samples include 2,029 natural ism data B.www.1001genomes.org for information on how to contribute).The genomes presented here integrate previously published subsets B. All acA range of Illumina platforms were used across several sequencing centers and over several years, so we instituted stringent quality controls to pare an initial set of over 1,200 sequenced genomes to a final set of 1,135 (see Data Release section). The data are the intersection of the MPI (SHORE) and GMI (GATK) pipelines, independently validated in our pilot studies . An averAfter filtering, the nuclear genomes contained 10,707,430 biallelic SNPs and 1,424,879 small-scale indels (up to 40\u00a0bp). This represents one variant on average every 10\u00a0bp of the single copy genome, which is the densest variant map for any organism, including the most recent release of the 1000 Genomes Project for humans . 2,842 bVIN3 in our collection and performed GWAS. We note first that there is little reason not to use full genome data, as permutation-based multiple-comparison thresholds can be uVIN3 . In contFT, SVP, FLC, all previously linked to flowering time variation , under which the genetic distance between individuals reflects only geographic distance. This model does not fit, as the peaks of pairwise differences do not reflect geography and two further Tanzanian accessions, Tanz-1 and Tanz-2, are relicts. Their sequences will be available in the next data release.The geographic distribution of relicts and non-relicts B confirmTo examine population structure in greater detail, we used ADMIXTURE to clustThe ADMIXTURE groups do not correspond to idealized randomly mating populations. There is a regional and variable pattern of IBD E. SimilaTo elucidate the historical processes that have shaped extant diversity, we estimated the distribution of coalescence times for the different populations using MSMC . The resA.\u00a0thaliana, with ADH, noted already the presence of surprisingly\u00a0diverged haplotypes, and interpreted it as evidence for balancing selection , many genes supported the alternative topology of a non-relict being closest to a relict.It is important not to exaggerate the divergence between relicts and non-relicts. In a survey of four-sample gene genealogies between the Col-0, Ler-0, and two random Iberian relicts, 26% place Col-0 closer to one relict than to Ler-0, rather than the two non-relicts together . Two addA.\u00a0thaliana population. It is therefore natural to search for footprints of selection related to adaptation to new environments, especially to climate, which varies considerably across the species range , suggesting that life-history differences contributed to the spread of non-relicts.In addition to these global patterns, we identified loci that may contribute to adaptive differences between Iberian relicts and non-relicts. We paired each relict with the geographically closest non-relict . Over 10egulator , and AP2elopment . Additiowith AP2 . Finallyand SOC1 . As expeand SOC1 . ConsistA.\u00a0thaliana, especially in marginal populations . We are releasing the following files at http://1001genomes.org/data/GMI-MPI/releases/v3.1: full VCF variant files for each accession, VCF files with quality reference calls, a combined Full Genome VCF file for all genomes, a standard merged group VCF file without invariant positions, a variant annotated\u00a0SnpEff VCF file, and individual pseudogenome files. Several tools to facilitate the use of this data are available under http://tools.1001genomes.org, including a strain ID web application, a viewer pf ADMIXTURE group membership, and a tool to retrieve specific regions of pseudogenomes in FASTA. Accession metadata, including group membership, are available under http://1001genomes.org/tables/1001genomes-accessions.html. See supplemental data release for additional tools and datasets.Data and tools are available at The members of The 1001 Genomes Consortium for this project are Carlos Alonso-Blanco, Jorge Andrade, Claude Becker, Felix Bemm, Joy Bergelson, Karsten M. Borgwardt, Jun Cao, Eunyoung Chae, Todd M. Dezwaan, Wei Ding, Joseph R. Ecker, Moises Exposito-Alonso, Ashley Farlow, Joffrey Fitz, Xiangchao Gan, Dominik G. Grimm, Angela M. Hancock, Stefan R. Henz, Svante Holm, Matthew Horton, Mike Jarsulic, Randall A. Kerstetter, Arthur Korte, Pamela Korte, Christa Lanz, Cheng-Ruei Lee, Dazhe Meng, Todd P. Michael, Richard Mott, Ni Wayan Muliyati, Thomas N\u00e4gele, Matthias Nagler, Viktoria Nizhynska, Magnus Nordborg, Polina Yu. Novikova, F. Xavier Pic\u00f3, Alexander Platzer, Fernando A. Rabanal, Alex Rodriguez, Beth A. Rowan, Patrice A. Salom\u00e9, Karl J. Schmid, Robert J. Schmitz, \u00dcmit Seren, Felice Gianluca Sperone, Mitchell Sudkamp, Hannes Svardal, Matt M. Tanzer, Donald Todd, Samuel L. Volchenboum, Congmao Wang, George Wang, Xi Wang, Wolfram Weckwerth, Detlef Weigel, Xuefeng Zhou.J.B., J.R.E., M.No., M.S., and D.W. coordinated the project. C.A.-B., C.B., J.B., J.C., E.C., T.M.D., J.R.E., A.M.H., S.H., M.H., A.K., P.K., N.W.M., M.Na., T.N., M.No., P.N., F.X.P., B.A.R., K.J.S., F.G.S., M.M.T., D.T., W.W., and D.W. selected and generated the samples. C.B., J.B., J.C., X.G., C.L., B.A.R., M.J., R.A.K., T.P.M., R.M., V.N., R.J.S., F.G.S., M.S., S.L.V., and X.Z. generated and handled sequence data. J.A., F.B., A.F., D.G.G., D.M., P.Y.N., A.P., F.A.R., A.R., C.W., and X.W. performed primary sequence analyses and variant annotation. M.E.-A., W.D., A.F., A.M.H., S.R.H., M.H., A.K., C.-R.L., M.No., H.S., and G.W. performed population genetic analyses. J.F., P.K., A.K., A.P., \u00dc.S., and C.W. curated the online resources and databases. K.M.B., D.G.G., A.K., M.No., and P.A.S. performed GWAS. M.E.-A., A.F., F.B., A.M.H., M.H., A.K., C.-R.L., M.No., A.P., H.S., C.W., G.W., and D.W. wrote the manuscript."} +{"text": "The co-author, Dr. Joanne A. Young\u2019s name has been changed to Dr. Jay A. Young."} +{"text": "This explains both the inability of Juno to bind vitamin B9/folic acid 9-binding pocket of an ancestral folate receptor molecule.The interaction between egg and sperm is the first necessary step of fertilization in all sexually reproducing organisms. A decade-long search for a protein pair mediating this event in mammals culminated in the identification of the glycosylphosphatidylinositol (GPI)-anchored glycoprotein Juno as the egg plasma membrane receptor of sperm Izumo1 et al. report the crystal structure of Juno and find that its overall fold is similar to that of folate receptors but with important differences in the ligand-binding site.Recent studies have shown that the GPI-anchored glycoprotein Juno is the egg plasma membrane receptor of sperm Izumo1. Here, Han FollowiJuno consists of nine \u03b1-helices and six short \u03b2-strands A, which 9 binding because they are also visible in the unbound forms of FR\u03b1 and FR\u03b2 9. These amino acids include FR\u03b1 F84 and G159\u2013W162, whose counterparts in loops 1 and 3 of Juno are completely disordered (Despite their overall similarity, there are striking local differences between the structure of Juno and that of FRs and RfBP. Whereas in the latter proteins three highly ordered loops generate a deep binding pocket for the respective ligands sordered A, as welsordered B.Although the Juno\u2013Izumo1 interaction is conserved in mammals Although the structure of Izumo1 is unknown, its amino-terminal Juno-binding region has been shown to be helical 9, but gained the ability to recognize Izumo1.Whereas FR homologues are found in all vertebrate classes, Juno appears restricted to mammals. Together with this observation, our studies suggest that the molecular basis of mammalian gamete recognition evolved from an ancestral FR that lost the ability to bind vitamin BConceptualization, K.N., G.J.W. and L.J.; methodology, L.H., K.N., L.J.; validation, E.B.; formal analysis, K.N., L.J.; investigation, L.H., K.N., H.S.A.H, E.B.; data curation, K.N., L.J.; writing \u2013 original draft, L.H., K.N., L.J.; writing \u2013 review and editing, L.H., K.N., H.S.A.H, E.B., G.J.W., L.J.; visualization, K.N., E.B., L.J.; supervision, G.J.W., L.J.; project administration, L.H., K.N., L.J.; funding acquisition, G.J.W., L.J."} +{"text": "Scientific Reports5: Article number: 1804310.1038/srep18043; published online: 12082015; updated: 08262016The original version of this Article contained errors in the spelling of the authors Dina N. Abd-Elshafy, Thomas Pietschmann, Ulf M\u00fcller-Ladner, Elena Neumann, Mahmoud M. Bahgat, Frank Pessler and Patrick Behrendt which were incorrectly given as Abd-Elshafy D. Nadeem, Pietschmann Thomas, M\u00fcller-Ladner Ulf, Neumann Elena, Bahgat M. Mohamed, Pessler Frank & Behrendt Patrick respectively.The \u2018How to cite this article\u2019 section quoted an incorrect abbreviation for Dina N. Abd-Elshafy.In addition, there were errors in the Author Contributions Statement,\u201cA.D. wrote the initial draft of the manuscript and modified by P.B. Experiments were planned and performed by A.D. and P.B. Initial figure drafts were created mainly by BM and A.K. and modified by P.B., M.U. and N.E. generated the primary cells and carefully reviewed and edited the manuscript. P.T. and P.F. substantial contributed to the experimental set-up, the manuscript and figure structure. All authors reviewed the manuscript before submission.\u201dnow reads:\u201cD.A. and M.B. wrote the initial draft of the manuscript and this was modified by P.B. Experiments were planned and performed by D.A. and P.B. Initial figure drafts were created mainly by M.B. and A.K. and modified by P.B., U.M. and E.N. generated the primary cells and carefully reviewed and edited the manuscript. M.B., T.P. and F.P. substantially contributed to the initial idea, the experimental set-up, the manuscript and figure structure. All authors reviewed the manuscript before submission.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Scientific Reports6: Article number: 25066; 10.1038/srep25066 published online: 04262016; updated: 06102016This Article contains errors.Marzena Ciechomska is incorrectly affiliated with \u2018Institute of Cellular Medicine Faculty of Medical Sciences, MRG 4th Floor Cookson Building Framlington Place, Newcastle Upon Tyne, NE2 4HH\u2019 and \u2018Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland\u2019. The correct affiliation is listed below:National Institute of geriatrics rheumatology and rehabilitation, Warsaw, Poland.In the Author Contributions statement,\u201cS.O.R. performed experiments and wrote the manuscript. M.C. performed some experiments and helped draft the manuscript. N.F. and S.P. performed some experiments. J.M.v.L. drafted and commented on the manuscript and had oversight of the project\u201d.should read:\u201cS.O.R. performed experiments and wrote the manuscript. MC, NF and SP performed some experiments and helped draft the manuscript. J.M.v.L. drafted and commented on the manuscript and had oversight of the project\u201d."} +{"text": "AbstractOenotheraxenogaura W.L.Wagner & Hoch for the species then known as Gauradrummondii (Spach) Torrey & A. Gray . However, the authors overlooked the availability of Gaurahispida Bentham (1840) for this species. Accordingly, we herewith make the appropriate new combination for this species, Oenotherahispida (Bentham) W.L.Wagner, Hoch & Zarucchi, and place Oenotheraxenogaura in synonymy.In 2007, Wagner and Hoch proposed the new name PageBreakOenotherasect.Gaurasubsect.Xenogaura is a distinctive allopolyploid species that occurs from eastern Texas south through Mexico as far south as Oaxaca. When the genus Gaura L. is recognized, the correct name for this species is Gauradrummondii (Spach) Torrey & A. Gray, which was used in the revision of the group by Oenothera is strongly supported as monophyletic only with the inclusion of Calylophus Spach, Gaura, and Stenosiphon Spach. These four groups also have in common a stigma that either is peltate to discoid, or is deeply to shallowly 4-lobed and then subtended by a more or less conspicuous peltate indusium. These data led Oenothera by including within it Calylophus, Gaura, and Stenosiphon. The new name Oenotheraxenogaura W.L.Wagner & Hoch was proposed in 2007 for this species when Gauradrummondii was transferred to Oenothera because use of Gauradrummondii is blocked by Oenotheradrummondii Hooker of sect. Oenothera. Within the protologue of their new combination, Wagner and Hoch did not cite any other taxonomic synonym. However, at that time, they failed to take into account Gaurahispida Bentham (1840), one of the synonyms included for Gauradrummondii by Gaurahispida to Oenothera and making the new combination. We herewith correct the mistake and make the appropriate new combination namely Oenotherahispida W.L.Wagner, Hoch & Zarucchi. Additionally, along with other synonyms cited by Raven and Gregory, Oenotheraxenogaura, a legitimate replacement name, is here placed into synonymy. Since Wagner and Hoch did not cite any taxonomic synonym, their Oenotheraxenogaura was not superfluous when published . Gauradrummondii (Spach) Torrey & A. Gray, Fl. N. Amer. 1: 519. 1838. Oenotheraxenogaura W.L.Wagner & Hoch, Syst. Bot. Monogr. 83: 213. 2007.Type. U.S.A. Texas: Travis Co., Austin, 1833\u20131834, T. Drummond III.36 . Note: the BM isotype is mounted on a sheet with two non-type collections of the same species: Purpus 3387 and Purpus 5383.Gauraroemeriana Scheele, Linnaea 21: 579. 1848.Type. U.S.A. Texas: Comal Co., New Braunfels, 1846, Ferdinand Roemer s.n. . The holotype at B was destroyed in World War II.Schizocaryacrispa Spach, Nouv. Ann. Mus. Paris 4: 384. 1835. Gauracrispa (Spach) D.Dietr., Syn. PI. 2: 1298. 1840.Type. Mexico: Tamaulipas, Matamoros, April 1831, J. L. Berlandier 2313 .PageBreakPageBreakstem but usually somewhat decumbent with several branches from the base and usually irregular branching above. Leaves in a basal rosette and cauline, 0.5\u20137.5 (-9.5) \u00d7 0.1\u20132.2 cm; subsessile; blade narrowly lanceolate to elliptic, margin subentire to shallowly sinuate-dentate. Inflorescence a spike. Flowers 4-merous, zygomorphic, opening near sunset; floral tube 4\u201314 mm; sepals 7\u201311(-14) mm; petals white, fading red, 6-10 mm; staminal filaments 4\u20138.5 mm, anthers 3-6 mm; style 12\u201326 mm. Capsule 7\u201313 \u00d7 3\u20135 mm, erect, the body ellipsoid or ovoid, 4-angled, distal half pyramidal, the base of the pyramidal portion distinctly bulging, then immediately and sharply constricted to the terete proximal part. Seeds (2-)3-4(-8), 2\u20132.5 \u00d7 1\u20131.25 mm, ovoid, usually flattened on one or several sides by crowding in the fruit, reddish brown. 2n = 28.Plant rhizomatous, perennial, forming extensive colonies, strigillose and often also villous. Stems 20\u201360(-120) cm tall, sometimes strict with a single unbranched main Oenotherahispida grows in sandy loam soils from the eastern half of Texas south through Mexico as far south Oaxaca. It is naturalized in Arkansas (Sevier Co.), coastal southern California, Georgia (Glynn Co.); its current status in both Arkansas and Georgia should be verified. It is considered an invasive species in California.Flowering from May through July, but sporadically as late as November. Oenotherahispida is the sole member of Oenotherasect.GaurasubsectionXenogaura. Oenotherahispida arose following interspecific hybridization between Oenotherasuffrutescens (Ser.) W.L.Wagner & Hoch (subsect. Campogaura (P. H. Raven & D. P. Gregory) W.L.Wagner & Hoch) and a species in subsect. Stipogaura (P. H. Raven & D. P. Gregory) W.L.Wagner & Hoch, possibly near Oenotheramckelveyae (Munz) W.L.Wagner & Hoch. Oenotherahispida was indeed Oenotheramckelveyae or a close relative, but that the staminate parent probably came from a lineage related to Oenotheradodgeniana Krakos & W.L.Wagner or Oenotheralindheimeri (Engelm. & A.Gray) W.L.Wagner & Hoch in subsect. Gaura (L.) W.L.Wagner & Hoch. Oenotherahispida is not easily distinguished morphologically from Oenotherasuffrutescens (subsect. Campogaura), with which it shares the character of a thick stipe, and occasionally hydridizes in Texas. Oenotherahispida is an aggressively rhizomatous perennial with fruits conspicuously bulging on the distal half (Oenotherahispida and Oenotherasuffrutescens can be difficult to distinguish we have included a capsule of the latter in the figure (Fig. Gauracoccinea Pursh. The label information corresponds to the published locality given and is marked as in the Bentham herbarium.tal half . Since Oure Fig. -F for coure Fig. . There a"} +{"text": "Asteliabanksii A.Cunn. was incorrectly stated as present in New Caledonia within the \u201cIncluded species and distribution\u201d section for Asteliasect.Isoneuron Skottsb. (page 112). The correct distribution of Asteliabanksii A.Cunn. is New Zealand. The Asteliasect.Isoneuron Skottsb. \u201cIncluded species and distribution\u201d section should read: Included species and distribution. New Caledonia: Astelianeocaledonica Schltr. New Zealand: Asteliabanksii A.Cunn.In Asteliamicrosperma Colenso pro parte type was incorrectly stated (page 113) as being made by Skottsberg on page 81 (1934). This type designation was made by Skottsberg on page 87 (1934). The designation of the Asteliamicrosperma type should correctly read:Additionally, the designation of the Asteliamicrosperma Colenso pro parte, Trans. & Proc. New Zealand Inst. 17: 251. 1885 (description of fruit only). Type: NEW ZEALAND. North Island. Seventy-mile Bush, between Norsewood and Dannevirke, County of Waipawa. 1884, W. Colenso s.n. (Lectotype: K , fruiting material in packet, designated by"} +{"text": "Biotechnology & Biotechnological Equipment, 27(4), pp. 3977\u20133981. http://dx.doi.org/10.5504/BBEQ.2013.0045Petranova, T., Sheytanov, I., Monov, S., Rashkov, R. and Kinov, P. (2013). Efficacy of Denosumab for Control of Bone Mineral Density and Microarchitecture in Postmenopausal Women with Osteoporosis: A One-Year Experience. When the above article was first published online, there was a discrepancy between the figures and the figure captions. This is now corrected as follows.Diagnosis Press and Taylor & Francis apologize for this error."} +{"text": "Protein and Cell.This article has been retracted. Although the article \u201cJames, T.Y., andBerbee, M.L. (2011). No jacket required new fungal lineage defies dress code.Bioessays. doi:10.1002/bies.201100110\u201d was cited, Bolla K unintentionallycopied smaller parts of the text. The authors apologize to the authors of theBioEssays paper and the readers of"} +{"text": "In pulsductance . This haductance . Agreeinductance , and thiductance . These eductance . As the"} +{"text": "The publisher apologizes for the following errors that were introduced during production.h.ohkura@ed.ac.uk) is the corresponding author.Sara M. R. Clohisey should not have been designated as the corresponding author. Hiroyuki Ohkura (There are errors in the current addresses for Sara M. R. Clohisey and Hiroyuki Ohkura. Sara M. R. Clohisey's current address is The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, United Kingdom. Hiroyuki Ohkura is not affiliated with The Roslin Institute."} +{"text": "Scientific Reports6: Article number: 25030; 10.1038/srep25030published online: 04292016; updated: 08252016Jean-\u00c9tienne Bassard was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article.The Acknowledgements section now reads:Brian C. King and Henrik Toft Simonsen were supported by SpotLight, a grant from the Danish Council for Strategic Research. Brian C. King, Konstantinos Vavitsas, Jean-\u00c9tienne Bassard and Bj\u00f6rn Hamberger were supported by the VILLUM research center of Excellence \u201cPlant Plasticity\u201d, the UCPH Excellence Programme for Interdisciplinary Research \u201cbioSYNergy\u201d, and by the Innovation Fund Denmark (previously the Danish Council for Strategic Research) grant \u201cPlant Power: Light-Driven Synthesis of Complex Terpenoids Using Cytochromes P450\u201d (12-131834). Nur Kusaira Binti Khairul Ikram was supported by a grant from Ministry of Higher Education, Malaysia and University of Malaya. Imaging data were collected at the Center for Advanced Bioimaging Denmark, University of Copenhagen. The authors would like to thank Drs. Mark Estelle and Dae-Kyun Ro for the ZmUBI1 and AaADS templates, respectively.The Author Contributions section now reads:B.C.K., K.V. and N.K.B.K.I. planned and performed the experiments, analyzed the data, and wrote the manuscript. J.S., L.B.S. and J-E.A.B. performed the experiments, analyzed the data, and reviewed the manuscript. B.H., P.E.J. and H.T.S. planned the experiments, analyzed the data, and reviewed the manuscript."} +{"text": "Nephrometric scoring systems aim to improve the manner in which tumoral complexity is measured and reported. Each system provides a way to objectively measure specific tumor features that influence technical feasibility. In this study we aimed to determine how nephrometric scoring systems tailored our approach to the surgical treatment of localised renal masses.Charts of the patients with localised renal tumors, who were managed by either open or robot-assisted nephron-sparing surgery between May 2010 and June 2012, were retrospectively reviewed. Nephrometric scores were calculated based on preoperative imaging findings. Perioperative data were recorded. Morphometric characteristics of the renal masses were compared. Additionally, the difference between surgical alternative subgroups in terms of morphometric variables and the predictive power of each scoring system in determining the details of the surgical plan were investigated. Furthermore, surgical preferences in different nephrometric categories were compared.Mean R.E.N.A.L. and P.A.D.U.A. scores of the tumors treated with robotic surgery were significantly lower than those managed by open surgery. R.E.N.A.L. nephrometry score showed significant differences between most of the surgical alternative subgroups. P.A.D.U.A. and C-index differences were significant only between robotic off-clamp and open clamped cases. Tumors that required open conversion had significantly higher mean R.E.N.A.L. and P.A.D.U.A. score. High R.E.N.A.L. score (cut-off: 6.5) and high P.A.D.U.A. score (cut-off: 7.5) were found to be significant predictors of the surgical route. Significantly more tumors with moderate R.E.N.A.L. score were managed through the open approach, while the significant majority of those with low R.E.N.A.L. and low P.A.D.U.A. score were operated by robotic assistance.R.E.N.A.L. and P.A.D.U.A. scores influenced our surgical treatment strategy for localized renal masses. High R.E.N.A.L. and P.A.D.U.A. scores increased the likelihood of an open NSS. With recent advances in imaging modalities, the incidental detection of localised renal cell carcinoma (RCC) has increased by almost 3.7% per year over the past several decades . Over 60Tumoral complexity remains the primary parameter according to which urologists determine the surgical approach and treatment strategy regarding renal masses. Technical details such as the route and the decision to cease renal blood flow temporarily during mass excision (warm ischemia vs. no ischemia) are under the influence of tumor characteristics. Morphometric scoring systems have been developed in an effort to standardize the nomenclature while discussing how \u201cchallenging\u201d the tumor is -8. In thRobotic technology has been installed at our hospital in May 2010 after which we have performed both open and robot-assisted NSSs. After IRB approval (IRB protocol no: 2013.189.IRB2.58), we reviewed the charts of the patients who have undergone NSS (open and robot-assisted) between May 2010 and June 2012 in our clinic. Data were retrospectively collected from a prospectively structured database. All operations were carried out by a single surgeon (TE), who is highly experienced in open NSS but has never performed pure laparoscopic surgery. He has accomplished a direct transition from open to robot-assisted laparoscopic surgery. Patient characteristics were analyzed, including demographic data, past medical history, mode of presentation, comorbidities and American Society of Anesthesiologists (ASA) score.Radiologic characteristics of the renal masses were scored retrospectively by a senior radiologist and urologist according to C-index method , R.E.N.AA total of 32 and 23 patients underwent robot-assisted and open NSS, respectively after the introduction of robotic technology in our clinic. Coexisting systemic medical problems were present in 38% (n\u2009=\u200921/55) of the patients, while 1 patient in the robotic group and 3 patients in the open surgery group had a solitary kidney.th and 12th ribs) extraperitoneal flank approach, as previously described [Open nephron-sparing surgery (ONSS) was performed using the intercostal (between 11escribed . Brieflyescribed . BleedinAll robot-assisted nephron-sparing surgeries (RANSS) were performed using the da Vinci surgical system with a 5-port approach, including two 8\u00a0mm ports for robotic instruments, one 12\u00a0mm port for the robotic scope, and 2 ports for the bedside assistant. RANSS\u2019s were carried out through the transperitoneal route with the patient in flank position. After colonic mobilization, Gerota\u2019s fascia was opened and tumor was adequately exposed. The decision to clamp renal pedicle was given during the operation, based on CT and/or MR images and intraoperative findings. If there was such a need, the renal artery was occluded with an external vessel loop secured with a hem-o-lok clip over a silicone tube . After dOperative data consisted of total operative time, estimated blood loss (EBL), warm-ischemia time (WIT) and adverse events. Final pathology reports were analyzed and thirty-day Clavien grade 2 and higher complications were recorded .We compared the morphometric characteristics of the renal masses managed by open and robot-assisted NSS. In addition, we investigated if nephrometric scores differed significantly between surgical alternative subgroups . Furthermore, surgical preferences in different nephrometric categories were compared. We also tested the predictive power of each scoring system in determining the details of the surgical plan.t test, Fisher\u2019s exact test and univariate linear models which were provided by the commercially available software (SPSS version 20).Statistical calculations were performed with the Demographic data of the patients enrolled to the study is shown in Table\u00a0Tumor size ranged between 0.5 \u2013 15\u00a0cm and the mean diameter did not differ significantly between two groups. Mean R.E.N.A.L. and P.A.D.U.A. scores were significantly higher in the open surgery group , double-j catheter insertion because of urinary extravasation (n\u2009=\u20091) and nasogastric tube insertion due to ileus (n\u2009=\u20092) were the recorded Clavien grade\u2009\u2265\u20092 complications in the robotic group. One patient in the ONSS group, who had a 9\u00a0cm solid mass bearing solitary kidney, suffered from a total of 3 Clavien grade\u2009\u2265\u20092 complications postoperatively. Blood transfusion in another patient was the remaining Clavien grade\u2009\u2265\u20092 complication in the open surgery group.Open conversion was necessary because of tumor size in 2, difficulty in dissection in 1 and uncontrollable bleeding in 2 cases. Converted cases had significantly higher mean R.E.N.A.L. and P.A.D.U.A. scores than the cases, which were accomplished with robotic assistance. However, the difference was insignificant in terms of mean C-index value .Histopathologic diagnosis was renal cell carcinoma (RCC) in 42 patients, (76%) with clear cell variant being the most common subtype. Angiomyolipoma (n\u2009=\u20095) represented the most frequently diagnosed benign lesion. Surgical margins were free of tumoral infiltration in all patients.The relationship between surgical alternatives and nephrometric data is schematized in Figure\u00a0After investigating the management strategy of the tumors in each R.E.N.A.L. and P.A.D.U.A. category , it was found out that, significantly more patients with low R.E.N.A.L. score and low P.A.D.U.A. score were managed with robot-assisted surgery whereas the majority of those with moderate R.E.N.A.L. score were treated with open NSS Table\u00a0.On univariate analyses, R.E.N.A.L. and P.A.D.U.A. scores were found to be significant predictors of the operative route (open vs. robot-assisted). R.E.N.A.L. score predicted the likelihood of open route with a sensitivity of 82.6% and specificity of 62.5% Figure\u00a0. None ofNephron-sparing surgery has been accepted as the ideal treatment of localised RCC, given the similar oncological outcomes to that of radical surgery -17. HoweRecently, three different scoring systems were developed to serve as a common vocabulary when discussing anatomic geometry and complexity of renal masses. Preoperative aspects and dimensions used for anatomic (P.A.D.U.A.) classification and R.E.N.A.L. scoring systems involve similar components and methodology, enabling a comprehensive description of the tumor size, polarity, anterior/posterior location and proximity to the collecting system ,8. The cNephrometric scoring systems have also been associated with certain measures of operative complexity such as ischemia time and complication rates. Waldert et al. reported a significant association between high P.A.D.U.A. scores (\u2265 10) and increased WIT (22 vs. 34\u00a0minutes) . SimilarApart from the documented power in predicting perioperative outcomes, these scoring systems also have the potential to influence surgical preferences, which covered the scope of this article. According to our results, mean R.E.N.A.L. and P.A.D.U.A. scores of the tumors managed by robotic assistance were significantly lower than those treated by open surgery. Although being lower in tumors managed by open approach, C-index values did not exhibit a statistically significant difference between open and robotic groups Table\u00a0. These dTumor size, estimated blood loss amounts and transfusion rates, which would be considered among the factors indirectly reflecting how \u201ctough\u201d the tumor was, did not differ significantly between open and robotic groups. Robot-assisted nephron-sparing surgeries lasted significantly longer than their open counterparts. However, this difference may not be regarded as a sign of tumoral complexity since recorded time in robotic surgeries included the \u201cdocking\u201d maneuvers.In our practice, the decision to occlude renal pedicle is given during the operation. Therefore, it might be regarded as an \u201cin-vivo\u201d validation of the preoperative morphometric information. Moreover, interrupting renal perfusion temporarily constitutes a major clinical concern since longer warm ischemia time has been associated with acute renal failure, decreased glomerular filtration rate and de-novo chronic kidney disease . In ordeOpen conversion during minimally invasive surgery might be regarded as another way of expressing the challenging nature of the tumor being handled. In our series, those tumors, for which open conversion was inevitable, had significantly higher mean R.E.N.A.L. and P.A.D.U.A. scores than those who were successfully treated in a minimally invasive fashion.On univariate analyses, P.A.D.U.A. and R.E.N.A.L. scores demonstrated sufficient predictive power in determining the route by which tumor was enucleoresected. High R.E.N.A.L. score and high P.A.D.U.A. score predicted the likelihood of an open NSS, with adequate statistical power. This finding was complemented by the significant difference between the number of patients in low, moderate R.E.N.A.L. and low P.A.D.U.A. categories with regard to the route that has been preferred for NSS Table\u00a0. In a siHowever, our findings do not mean that we preferentially use the R.E.N.A.L. or the P.A.D.U.A. system for preoperative morphometric assessment. Based on the available literature, there is no clear advantage of one scoring system over the others regarding surgical preferences and perioperative outcome. As the number of patients in each sub-category increase, the C-index differences that were stated as insignificant might gain statistical significance. Therefore, it is hard to draw strict conclusions about the superiority of R.E.N.A.L. or P.A.D.U.A. scoring systems based on our results.Our study is unique in that it focuses on the utility of morphometric scoring systems in tailoring the surgical approach rather than perioperative outcomes or oncologic results. Moreover, only nephron-sparing surgeries performed by a single surgeon through the open or robot-assisted laparoscopic route were taken into consideration. At last but not the least, we tested the discriminative power of all three scoring systems that are currently being utilized across the globe. However, this data reflects the experience of a single surgeon, who is proficient in open NSS and currently in the initial phase of the learning curve for robotic NSS, which may limit the reproducibility of our findings. Our statistical findings are also handicapped by the retrospective study design and small sample size. Another criticism is the lack of strictly defined indications about the details of the surgical strategy. Route of access and the decision to clamp the renal hilum during enucleoresection depended on a variety of factors such as patient profile , tumor characteristics and surgeon preference. In the early days of the robotic era in our hospital, smaller (cT1a), cortical and exophytic tumors that were located anteriorly, below or above the hilar plane were scheduled for robot-assisted NSS while more complicated tumors were managed by open NSS in order to ensure a reasonable warm ischemia time. However, as our experience grew, we started doing robot-assisted NSS for more challenging tumors. This selection bias, which can be understandable within the context of the learning curve, should be considered while interpreting our results. Future prospective studies enrolling higher number of patients will more precisely highlight the importance of adapting preoperative morphometric evaluation into routine clinical practice.R.E.N.A.L. and P.A.D.U.A. systems influenced the way we handled localised renal masses. High R.E.N.A.L. and P.A.D.U.A. scores increased the likelihood of an open NSS. Although R.E.N.A.L. score differed significantly between surgical alternative subgroups, it did not exhibit sufficient statistical power to be a significant predictor of pedicle clamping during NSS. Morphometric evaluation, especially R.E.N.A.L. and P.A.D.U.A. systems, seem to have a clear impact on the decision-making process for the surgical treatment of localised renal tumors. Further prospective studies enrolling higher number of patients may establish the actual predictive power of morphometric scoring systems in the surgical planning of renal masses.RCC: Renal cell carcinoma; NSS: Nephron-sparing surgery; RENAL: Radius, exophytic/endophytic, nearness, anterior/posterior, location; PADUA: Preoperative aspects and dimensions used for anatomic classification; C-index: Centrality index; ASA: American Society of Anesthesiologists; ONSS: Open nephron-sparing surgery; RANSS: Robot-assisted nephron-sparing surgery; EBL: Estimated blood loss; WIT: Warm-ischemia time.The authors declare that they have no conflict of interests.TE: Conception and design, acquisition of data, analysis and interpretation of data, carried out morphometric scoring, critical revision of the manuscript for scientific and factual content, supervision. \u00d6A: Conception and design, acquisition of data, analysis and interpretation of data, statistical analysis, drafting the manuscript, critical revision of the manuscript for scientific and factual content. AM: Conception and design, acquisition of data, helped to draft the manuscript. MV: Conception and design, acquisition of data, analysis and interpretation of data, carried out morphometric scoring. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2490/13/63/prepub"} +{"text": "Dr. Els Louagie is not included in the author byline. She should be listed as the seventh author and affiliated with Department of Rheumatology, Ghent University, Ghent, Belgium. The contributions of this author are as follows: Performed the experiments, analyzed the data, and contributed reagents/materials/analysis tools.http://www.kanker.be/grants) (G.L.), by the Fund for Scientific Research (FWO) (G.0187.13) (http://www.fwo.be/en/fellowships-funding/research-projects/research-project/) (G.L.) and by the BOF of Ghent University (BOF11/GOA/005) (http://www.ugent.be/nl/onderzoek/financiering/bof/goa/overzicht.htm) . A.V.A, J.F., M.V. are supported by the Institute for the Promotion of Innovation through Science and Technology Flanders (IWT-Vlaanderen) (http://www.iwt.be/subsidies/sb). S.T. is supported by the BOF of Ghent University. T.K. is supported by the FWO. E.L. is supported by the Interuniversity Attraction Poles Programme of the Belgian Science Policy Office (IAP project DevRepair). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The Funding section should read: This work was supported by grants from the Foundation against Cancer, a foundation of public interest (2010\u2013166) ("} +{"text": "The RO1 HL113178 grant is missing from the Funding section.The complete, correct Funding section is: This work is supported by grants from the NIH/NHLBI RO1 HL090829 (V.P.K.), 2RO1 HL071106 (V.P.K.), RO1 HL114085 (V.P.K.),and RO1 HL113178 (E.A.G.), DOD IDEA TS030012 (V.P.K.), the LAM Foundation (V.P.K. and E.A.G.), and the American Thoracic Society (E.A.G.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."} +{"text": "The Research Associateship program of the Joint Committee on Powder Diffraction-International Centre for Diffraction Data at NBS/NIST was a long standing (over 35 years) successful industry-government cooperation. The main mission of the Associateship was to publish high quality x-ray reference patterns to be included in the Powder Diffraction File (PDF). The PDF is a continuing compilation of patterns gathered from many sources, compiled and published by the ICDD. As a result of this collaboration, more than 1500 high quality powder diffraction patterns, which have had a significant impact on the scientific community, were reported. In addition, various research collaborations with NBS/NIST also led to the development of several standard reference materials (SRMs) for instrument calibration and quantitative analyses, and computer software for data collection, calibration, reduction, for the editorial process of powder pattern publication, analysis of powder data, and for quantitative analyses. This article summarizes information concerning the JCPDS-ICDD organization, the Powder Diffraction File (PDF), history and accomplishments of the JCPDS-ICDD Research Associateship. In the late thirties, the powder x-ray diffraction technique was recognized as a powerful technique for phase identification/chemical analysis. In 1938, Hanawalt, Rinn, and Frevel . Hull stIn the late 1930s, a meeting was held at Gibson Island, MD to discuss the formation of an ongoing file of x-ray powder diffraction patterns of chemical phases for use in identifying materials. This meeting was arranged by Wheeler P. Davey of Pennsylvania State College. Herbert Insley and Howard McMurdie were invited to the meeting as NBS was known to have a growing interest in the subject. In 1941, the Joint Committee on Chemical Analysis by X-Ray Diffraction Methods, part of the American Society for Testing and Materials (ASTM), was founded. This committee, which was also sponsored by the British Institute of Physics, asked Davey to direct an extensive project to coordinate research and publication activity of the diffraction patterns worldwide [ASTM published the first set of data, consisting of 4000 cards in 1941, covering some 1300 compounds. An extensive set of some 4500 supplement cards was completed around 1945. These cards contained data for inorganic, organic and mineral crystalline phases and included interplanar spacings, relative intensities, and, when available, indexing, unit cell, specific gravity, and optical property data.The purpose of this committee was to collect, edit, publish, and distribute primary references for x-ray powder diffraction analysis/identification of crystalline materials. This compilation is now commonly known as the Powder Diffraction File\u2122 (PDF). Many scientific associations and societies, including the ASTM, supported the initial effort. Continued additions and regular publication of \u201csets\u201d followed. By 1969, the committee was constituted as a Pennsylvania nonprofit corporation under the title of the Joint Committee on Powder Diffraction Standards (JCPDS). In 1978, the current name\u2014International Centre for Diffraction Data\u2014was adopted. The ICDD Mission Statement is \u201cThe International Centre for Diffraction Data will continue as the world center for quality diffraction data to meet the needs of the technical community, ICDD promotes the applications of materials characterization methods in science and technology by providing a forum for the exchange of ideas and information.\u201dToday, nearly 300 international scientists from industrial, academic and governmental laboratories comprise the active membership from which the organization draws its Board of Directors, committees, and subcommittees. The members, who are volunteers, are actively engaged in developing the field of x-ray powder diffraction and related disciplines. They gather twice annually to discuss various technical issues related to powder diffraction methods, and editorial issues related to the PDF, and to organize, plan, and review policies and procedures within the ICDD organization. The Technical Committee consists of three categories of subcommittees, namely, Materials Subcommittee , Characterization Methods & Tools Subcommittee , and ICDD Activities Subcommittee . A paid scientific and administrative staff, located at the headquarters in Pennsylvania, is responsible for the production of the various databases offered by the ICDD.The ICDD financially supports scientific activities worldwide. Amongst these activities, it maintains a Grants-in-Aid program in order to provide high quality data and develop search techniques for the identification of materials by powder diffraction methods. In the area of education, the ICDD \u201chas established a Crystallography Scholarship Fund, now known as the Ludo Frevel Crystallography Scholarship Fund.\u201d The function of this fund is \u201cto encourage promising graduate students to pursue crystallographically oriented research.\u201dIn the late forties, there was considerable criticism about duplicate patterns on some phases which were not always consistent as they were made by different methods, and there was always a call for coverage of more compounds. For example, at a meeting of the American Crystallographic Society in 1948 a prominent crystallographer called for the whole file to be redone. It was recognized that there was a need for an organized scientific group to undertake a systematic review of the file, and to prepare quality powder diffraction reference standards. Although many of the patterns obtained from the literature and other sources were adequate, there was a need was to prepare data using reproducible, controlled conditions of specimen preparation and the best recording instrumentation available. Under the sponsorship of the ASTM, the Joint Committee on Chemical Analysis by X-Ray Diffraction Methods of the ASTM, A.S.X.-R.E.D., and British Institute of Physics, a Research Associateship was established at NBS, effective July 18, 1949 [The Research Associateship was under the direct supervision of H. F. McMurdie, then Chief of the Constitution and Microstructure Section of the Division of Mineral products, and members of this special group were appointed by the JCPDS-ICDD, consisting of Chairman W. L. Fink (Aluminum Company of America), L. L. Wyman , W. P. Davey, and L. K. Frevel . Eleanor Tatge was named to the Associateship. Her primary responsibility was to review conflicting data in the card file issued by the Joint Committee and undertake the selection of correct patterns or to make new patterns of standard material After McMurdie\u2019s retirement, he was appointed by the JCPDS-ICDD to be the main contact with ICDD and H. Swanson became the principal scientist. In 1976 Marlene Morris became the contact and principal scientist. In the early seventies, Camden Hubbard of NBS was appointed as the liaison officer between the Associateship and NBS. He provided distinguished leadership in ensuring the quality of the patterns, as well as keeping abreast with the state-of-the-art computer technology and x-ray diffraction instrumentation and techniques.The members of the Associateship from the beginning to its conclusion in 1986, included : Simon J. Carmel, Eloise H. Evans, Ruth K. Fuyat, Nancy T. Gilfrich, Donna M. Gladhill, Johan H. de Groot, Kimberly Hill, Camden R. Hubbard, Howard F. McMurdie, Marlene C. Morris (Cook), Boris Paretzkin, Harry S. Parker, Nikos P. Pyrros, Eleanor Tatge, Roger P. Stinchfield, Howard E. Swanson, George M. Ugrinic, Linda Ulmer, and Winnie Wong-Ng. A few photographs of these members and outside colleagues are shown in In the early days, the PDF databasePowder diffraction patterns are compiled from journals, the ICDD Grant-in-aid Program, other grants and scientific contributions. The patterns are edited for correctness, and reviewed for quality and uniqueness by various experts of the field. Subfile mark assignment was also conducted by the editors. The careful editorial process assures that the ICDD maintains the highest standards for accuracy and quality of its database .The PDF currently (2001 release) consists of 51 sets of data and 136 895 patterns in Karlsruhe and NIST). The file covers ceramic mineral, metal/alloy, organic and other inorganic crystalline materials. The PDF is subdivided into various subfiles, such as inorganic, mineral, organic, metal/alloy, common phases, ICSD, forensic, education, zeolite, explosive, superconductors, cement, corrosion, polymer, detergent, pigment, pharmaceutical, ceramics, and a separate subfile for the NBS patterns.The primary mission of the JCPDS-ICDD Research Associateship was to produce standard reference x-ray powder diffraction patterns for phase identification. Several additional research projects which were important for improvement of the quality of patterns and methodology were also identified and conducted under the supervision of the NBS scientific staff. These projects included the development of computer software for data collection and reduction, software to aid the powder pattern evaluation and editorial process, and quantitative phase analysis. Another area of important research area was the development of standard reference materials (SRM\u2122) for instrument calibration and quantitative phase analysis.These NBS standard patterns were produced using reproducible, controlled conditions of specimen preparation, and the best recording methods and instrumentation available. The method of producing these patterns has been described in detail by McMurdie et al. . The con2 (quartz), Al2O3 (corundum) etc., and to compare them against the reference patterns produced by the Associateship. In later years, with the introduction of computer-controlled experimental systems, and with the computer-based search-match procedures, this testing became more intensive. During the development of computer unit cell indexing routines, it was further recognized that only high quality data such as the Associateship patterns would consistently yield correct results.The patterns prepared by the NBS Associateship were used for various applications. For example, they have often been singled out for reference when testing new methods involving x-ray diffraction. Also, as a final step in the alignment of any x-ray powder diffraction instrument, it is a common practice to record the pattern of some common materials, e.g., SiOBecause of the extraordinary quality of the patterns produced by the Associateship, they have been collected under a single cover known as the NBS Patterns. This collection contains patterns for many compounds commonly encountered in scientific and industrial studies. Although these patterns have appeared in Circulars and Monographs published by the NBS, several of these publications were out of print at the time the NBS Patterns Book appeared. Also, earlier patterns have been revised as new techniques became available. A minifile called \u2018NBS\u2019 subfile was created in the PDF database, and these patterns also served as a minisearch file along with a specific search manual. The NBS patterns have also been used as an excellent teaching tool in the use of powder diffraction methods for compound identification. (The full PDF with a large number of patterns often led the beginners into many confusing pattern similarities.) These data cover many common laboratory chemicals and minerals so that in some cases identifications of common materials can be made quickly without a search through the full data collection. Teachers in classrooms often have found this minifile useful because most of the materials reported are readily available for classroom experiments.d-spacings, intensity values of the diffraction peaks, references, sample preparation procedure, another piece of information which is reported for a large number of patterns prepared by the Associateship is the reference intensity ratio (RIR). RIR is an instrument-independent constant for use in the quantitative phase analysis by the internal standard method [\u03b1-Al2O3, was chosen as the internal standard for preparing the reference intensity ratio (RIR). When the reference standard is corundum, RIR is known as the I/Ic. Recommended methods for accurate measurement of RIR constants were discussed by Hubbard and Snyder [In order to obtain a basis for an approximate quantitative analysis of mixtures, a comparative strength of peak height intensities from different materials is necessary. In addition to the crystallographic data, d method ,10. Thes\u03b8 values using internal and/or external calibration parameters), PLOT (perform both hardcopy and interactive plots), and PROFILE REFINEMENT (refined peak positions and their intensities). This software suite was critical for the Associateship members to generate high quality x-ray diffraction patterns. Many requests have been received from outside laboratories concerning the availability of these software products.The production of standard x-ray diffraction patterns at NBS imposed special requirements and specific demands in the automated data collection and data processing. The data collection system AUTO and the Fundamental Parameter Approach convolution algorithm [\u03b8 than those from Si [d-spacing) standard and is best used as pressed samples having a high degree of preferred orientation in which the 00l reflections have significant intensity. Both these SRMs were d-spacing standards which can be used as external or internal calibrants and are in high demand. External and internal standard calibration are important procedures for achieving high accuracy in x-ray powder diffraction studies. The theoretical basis as well as procedures for obtaining calibration curves, methods and examples of selecting SRMs, and procedures of sample preparation with these standards are described by McMurdie et al. [6) for profile calibration, SRM 674 , and SRM 1878 (respirable quartz).Based on the NBS/JCPDS collaborations, several standard reference materials (SRMs) were developed for powder x-ray diffraction measurements \u201315. Amonlgorithm . SRM 675 from Si . They wee et al. and Wonge et al. . Other shttp://www.nist.gov/srm).Today a large collection of SRMs is available for powder x-ray diffractometry. Further development of new SRMs as well as recertification of existing ones continues under the leadership of J. P. Cline. He has developed a new SRM 1976 and recertified three whose stock was exhausted. Their purpose, cost, and further information on these SRMs are available in the SRM office of NIST. Further information can be obtained via the Website . A proposal which entailed a five year plan of creating computer code, designing and testing a prototype database, and reevaluating the historical data of Sets 1\u201332 was submitted by this subcommittee and was approved by the ICDD Board of Directors. The computerization was carried out cooperatively by both the ICDD and NBS staff. The NBS staff provided the technical guidance for the entry process and wrote the key computer programs which were necessary for the creation and critical evaluation of the computer database. Members of the ICDD staff performed the critical review, developed editorial procedures, and provided additional data entry. Work on the proposal began at NBS with the design of the database format (structure of the database), selection of data items to be included, and development of a computer program to evaluate the data entries. The format selected for the PDF database was that of NBS CRYSTAL DATA developeIf NBS*AIDS80 finds a data or format inconsistency (\u201cerror\u201d), then the data must be corrected and reprocessed. Patterns with unresolvable errors were added to a list of questionable phases for remeasurement. The program also gives warnings of possible errors in the data, each of which are reviewed, and, if necessary, editorial changes are made. Throughout the years, this program has been updated extensively to meet the need of a variety of new classes of material, and the state-of-the-art computer database and file structure. It still remains as the key editorial program for producing the PDF. Because of this sophisticated computer program, the review process utilized today is considerably more stringent than in former years [http://www.icdd.com.The full-scale project of computerization and critical evaluation of PDF data Sets 1\u201332 was initiated in the beginning of 1982. All data entering the PDF beginning with data for Set 33 were not part of the historical review but were evaluated and computerized during the editorial and publication process. Since 1984, products such as data books and data cards (discontinued to date) have been produced directly from the PDF database. Today, all PDF products are generated directly from the database, including a recently released relational database product. Further information about the ICDD products can be located at the WEBSITE: d-spacings, etc. By use of optimum packing and access algorithms, the various searches operated at speeds highly convenient to the user. Currently, the CD-ROM products are the most popular products by ICDD.Another development of the ICDD database concerns data storage using a CD-ROM disk. In the mid-eighties, there was increasing use of the PDF in computer readable form, but the limited amount of disk space available on most commercial powder diffractometer systems limited the use to a small subset of the total PDF. A product proposal was submitted by W. Wong-Ng and C. Hubbard to the JCPDS-ICDD Board of Director in the early eighties, followed by several presentations concerning the advantages and various product opportunities of using the state-of-the-art CD-ROM technology. The availability of low-cost CD-ROM systems offered an attractive alternative to conventional disk media . Under tWith the development of standards, software, automated systems and numerous publications of data and methods, more and more laboratories became capable of measuring and analyzing high quality reference patterns. Thus, the mission of the ICDD Research Associate Program was believed to be accomplished in 1986, and part of the staff of the ICDD Associateship was transferred to the ICDD Headquarters. Following this success, a 3-year program at NBS to produce high quality x-ray patterns of important ceramic phases was established. This program was administered by C. R. Hubbard and A. L. Dragoo, with W. Wong-Ng was in charge of the day-to-day operation. The project was directed toward the production of x-ray diffraction data for important ceramic phases, which might find applications in engine components, cutting tools, etc. This project which was an integral part of the program at NBS to develop measurement methods and data to further the manufacture and use of ceramic materials, included a comprehensive review and upgrade of data for selected borides, carbides, silicides, nitrides, oxynitrides, selenides, tellurides and oxides. Samples for x-ray characterization were obtained through collaboration with other research laboratories, and by synthesis at NBS. For example, cooperation with the Phase Diagram Project, jointly sponsored by the American Ceramic Society and NBS, was initiated to identify new phases of interest, to synthesize selected new phases, and to develop improved editorial procedures for both the PDF and the Phase Diagram Database .Tc materials has been an important activity of the superconductor community in the past 15 years. Many high Tc superconductor phases were reported in the literature, including new structure types as well as single phases and solid solutions isomorphous to known structures. The development of microwave materials for wireless communications has been steadfast. There has also been intense development of magnetic and ferroelectric materials for thin film applications. All of these fields are developing rapidly. The availability of high-quality powder patterns of carefully-prepared and well-characterized materials will meet the expressed needs of researchers in these fields.At the conclusion of the Advanced Ceramics Program, further collaborations continued through the ICDD Grants-in-Aid Program. This ongoing project compliments the NIST existing program of phase equilibria of electronic materials. In recent years, several important classes of electronic materials have had a large impact on the relevant industries. The characterization of high In collaboration with J. Kaduk of BP-Amoco Research Center, patterns were analyzed using the Rietveld refinement technique . Data prFruitful collaborations between NIST and ICDD will continue for many years to come. In addition to the Grants-in-aid projects for the preparation of standard reference x-ray patterns for inclusion in the PDF, several NIST staff members are currently actively involved in the ICDD Scientific Subcommittee activities. Howard McMurdie continues to be the editor for the patterns of inorganic materials. He also works on the American Ceramic Society\u2019s (ACS) compilation of phase diagrams. Collaborations between the NIST, ICDD and Ceramics Society database efforts have also been planned. For example, linkage of their respective databases would provide the user with the ability to search multiple databases in an integrated fashion. This cross-search capability will have an important impact on material characterization and material design.46 (4), 318 (1951), Data on 8 phases.H. E. Swanson and E. Tatge, J. Res. Natl. Bur. Stand. (U.S.) H. E. Swanson and E. Tatge, NBS Circular 539, Vol. 1 (1953), data for 54 inorganic substances.H. E. Swanson and R. K. Fuyat, NBS Circular 539, Vol. 2 (1953), data for 30 inorganic substances.H. E. Swanson, R. K. Fuyat, and G. M. Ugrinic, NBS Circular 539, Vol. 3 (1954), data for 34 inorganic substances.H. E. Swanson, R. K. Fuyat, and G. M. Ugrinic, NBS Circular 539, Vol. 4 (1955), data for 42 inorganic substances.H. E. Swanson, N. T. Gilfrich, and G. M. Ugrinic, NBS Circular 539, Vol. 5 (1955), data for 45 inorganic substances.H. E. Swanson, N. T. Gilfrich, and M. I. Cook, NBS Circular 539, Vol. 6 (1956), data for 44 inorganic substances.H. E. Swanson, N. T. Gilfrich, and M. I. Cook, NBS Circular 539, Vol. 7 (1957), data on 53 substances.H. E. Swanson, N. T. Gilfrich, M. I. Cook, R. Stinchfield, and P. C. Parks, NBS Circular 539, Vol. 8 (1959), data for 61 substances.H. E. Swanson, M. I. Cook, T. Isaacs, and E. H. Evans, NBS Circular 539, Vol. 9 (1960), data for 43 substances.H. E. Swanson, M. I. Cook, E. H. Evans, and J. H. deGroot, NBS Circular 539, Vol. 10 (1960), data for 40 substances.H. E. Swanson, M. C. Morris, R. P. Stinchfield, and E. H. Evans, NBS Monograph 25, Sec. 1 (1962), data for 46 substances.H. E. Swanson, M. C. Morris, R. P. Stinchfield, and E. H. Evans, NBS Monograph 25, Sec. 2 (1963), data for 37 substances.H. E. Swanson, M. C. Morris, E. H. Evans, and L. Ulmer, NBS Monograph 25, Sec. 3 (1964), data for 51 substances.H. E. Swanson, M. C. Morris, and E. H. Evans, NBS Monograph 25, Sec. 4 (1966), data for 103 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, and E. H. Evans, NBS Monograph 25, Sec. 5 (1967), data for 80 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, and E. H. Evans, NBS Monograph 25, Sec. 6 (1968), data for 60 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, and E. H. Evans, NBS Monograph 25, Sec.7 (1969), data for 81 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, and E. H. Evans, NBS Monograph 25, Sec. 8 (1970), data for 81 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, E. H. Evans, and B. Paretzkin, NBS Monograph 25, Sec. 9 (1971), data for 63 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, E. H. Evans, and B. Paretzkin, NBS Monograph 25, Sec. 10 (1972), data for 84 substances.H. E. Swanson, H. F. McMurdie, M. C. Morris, E. H. Evans, and B. Paretzkin, NBS Monograph 25, Sec. 11 (1974), data for 70 substances.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, J. H. deGroot, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 12 (1975), data for 57 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, J. H. deGroot, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 13 (1976), data for 58 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, J. H. deGroot, R. Newberry, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 14 (1977), data for 68 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, J. H. deGroot, B. S. Weeks, R. J. Newberry, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 15 (1978), data for 112 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, J. H. deGroot, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 16 (1979), data for 86 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, C. R. Hubbard, and S. J. Carmel, NBS Monograph 25, Sec. 17 (1980), data for 54 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, H. S. Parker, N. C. Panagiotopoulos, and C. R. Hubbard, NBS Monograph 25, Sec. 18 (1981), data for 58 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, H. Parker, N. P. Pyrros, and C. R. Hubbard, NBS Monograph 25, Sec. 19 (1982), data for 51 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, H. S. Parker, N. P. Pyrros, and C. R. Hubbard, NBS Monograph 25, Sec. 20 (1984), data for 71 substances.M. C. Morris, H. F. McMurdie, E. H. Evans, B. Paretzkin, H. S. Parker, W. Wong-Ng, D. M. Gladhill, and C. R. Hubbard, NBS Monograph 25, Sec. 21 (1985), data for 92 substances.1 (1), 77 (1986), data on 20 phases.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, W. Wong-Ng, L. Ettlinger, and C. R. Hubbard, Powder Diffraction 1 (2), 64 (1986), data on 20 phases.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, W. Wong-Ng, L. Ettlinger, and C. R. Hubbard, Powder Diffraction 1 (3), 265 (1986), data on 15 phases.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, W. Wong-Ng, and C. R. Hubbard, Powder Diffraction 1 (4), 334 (1986), data on 17 phases.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, W. Wong-Ng, Y. Zhang, and C. R. Hubbard, Powder Diffraction 2 (1), 41 (1987), data on 17 phases.H. F. McMurdie, M. C. Morris, E. H. Evans, B. Paretzkin, W. Wong-Ng, Y. Zhang, and C. R. Hubbard, Powder Diffraction 2 (2), 106 (1987), data on 15 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, C. R. Hubbard, A. L. Dragoo, and J. M. Stewart, Powder Diffraction 2 (3), 191 (1987), data on 16 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, Y. Zhang, K. L. Davis, C. R. Hubbard, A. L. Dragoo, and J. M. Stewart, Powder Diffraction 2 (4), 257 (1987), data on 15 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, Y. Zhang, K. L. Davis, C. R. Hubbard, A. L. Dragoo, and J. M. Stewart, Powder Diffraction 3 (1), 47 (1988), data on 15 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, Y. Zhang, C. R. Hubbard, A. L. Dragoo, and J. M. Stewart, Powder Diffraction 3 (2), 113 (1988), date on 14 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, C. R. Hubbard, and A. L. Dragoo, Powder Diffraction 3 (3), 179 (1988), data on 14 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, M. A. Kuchinski, and A. L. Dragoo, Powder Diffraction 3 (4), 247 (1988), data on 14 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, M. A. Kuchinski, and A. L. Dragoo, Powder Diffraction 4 (1), 40 (1989), data on 14 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, M. A. Kuchinski, and A. L. Dragoo, Powder Diffraction 4 (2), 106 (1989), data on 15 phases.W. Wong-Ng, H. F. McMurdie, B. Paretzkin, M. A. Kuchinski, and A.L. Dragoo, Powder Diffraction Since the 1950s when the Research Associateship was established, it has produced nearly 2000 high quality standard reference patterns. The NBS patterns were published in NBS Circular 539 (10 volumes) and NBS Monographs , PDF database, NBS circulars, as well as the early issues of the journal Powder Diffraction. The following is a list of the principal publications from the Research Associateship program."} +{"text": "AbstractCynoglossum sensu lato and its segregate genera: Adelocaryum, Afrotysonia, Kuschakewiczia, Lindelofia, Mattiastrum, Paracaryum, Rindera, Solenanthus, Trachelanthus, and their synonyms. Names and designations that were not validly published in the cited place, and later isonyms, are accounted for when they have been included in the International Plant Name Index (IPNI). Problems with IPNI entries, including errors and omissions, are discussed, and the hope is expressed that the present inventory may be of use for fixing them.An inventory is presented of all names so far validly published in green) pertaining to Cynoglossum sensu lato, for which complete synonymies are provided; and names (in orange) pertaining to other genera but published under Cynoglossum or its segregates. They are listed together with their basionym and the corresponding correct name (if it exists), but without complete synonymy. Acceptable, potentially correct names appear in bold-face type, both under a broadly defined Cynoglossum and under one or more of its segregates. When a name was published for a new taxon, original material is indicated, usually by direct quotation from the protologue. New type designations are exceptional (two cases), whereas former type designations are cited whenever known. Furthermore, types and original specimens, especially when their digital images are available online, are mentioned with their locations and accession numbers. Comments are added whenever appropriate, especially to explain nomenclatural assessments that are not self-evident.The inventory, generated from a list of structured data, is presented in two Supplements, as a searchable HTML document comprising a sequence of entries with internal cross-links and links to external sources, in particular to protologues accessible online or, copyright restrictions permitting, made available as scanned documents via DOIs, and as machine-readible file. With minor exceptions, all names have been verified in their original place of publication, and all were nomenclaturally assessed. Colour coding is used to distinguish between names (in Cynoglossum (Boraginaceae sensu stricto) consists of more or less short-lived, predominantly biennial herbs. Anthers and stigma are usually included in the corolla tube, which at the throat is closed by hollow scales or folds called fornices. The fruit separates at maturity into more or less roundish, mostly glochid-bearing dry mericarpids .The cosmopolitan genus Cynoglossum (and thus of the main part of the Cynoglosseae) is controversial. Based on an unresolved relationship of taxa traditionally defined by morphological traits, mainly of the fruit, authors such as Greuter & Burdet ; at the other extreme, authors such as Mattiastrum and Paracaryum.Delimitation of the genus urdet in plead foCynoglossum sensu stricto, as traditionally defined (mainly by fruit characters), is clearly polyphyletic. Even when some discordant elements currently assigned to Cynoglossum are removed, Cynoglossum sensu stricto remains paraphyletic, as morphologically deviating genera such as Paracaryum, Paracynoglossum, Pardoglossum and Solenanthus are nested within it. This means that the characters traditionally used for delimiting genera are insufficient to define monophyletic groups. Only if and when additional, phylogenetically meaningful features are found will it be possible to define natural units, potentially of generic rank, within Cynoglossum sensu lato. This has not happened as yet but is an important task for the future, combined with DNA sequence analyses of those species that have not so far been investigated.In recent years, DNA sequencing studies have tenCynoglossum sensu lato. We decided to include into that inventory any and all combinations published under either Cynoglossum itself or the name of a genus pertaining to Cynoglossum sensu lato, with their respective basionyms, even when \u2013 on the basis of current phylogenetic understanding \u2013 we do not consider that the corresponding taxon belongs to the latter. In order to assess the nomenclatural status of every name, we had to verify the original publication of each, i.e. its protologue. Therefore,it appeared logical to include into our inventory the protologue information relating to the respective original material. As a corollary, we endeavoured to find and put on record as many subsequent type designations as possible. Needless to say, the tracing and incorporation of this additional information increased our self-set task manifold \u2013 but we believe that the added value conferred to the inventory justifies our effort.To facilitate future research, it appeared to be a worth-while task to establish a complete inventory of taxa so far described and validly named, at any rank, within Cynoglossum sensu lato we give a complete synonymy. For other, non-Cynoglossum taxa we only list names published under genera that pertain to Cynoglossum sensu lato, plus their basionym, if any. This distinction forced us to assess the appropriate placement of the named taxa, whether within or outside of Cynoglossum sensu lato, which is a taxonomic decision \u2013 and, as it turned out, not always a trivial one. Once we realised that we had lost our taxonomically virgin status we decided that we might just as well abandon our self-imposed restraint and introduce taxonomic assessment throughout, appreciating that users are keen to be given that kind of guidance. Since the present authors disagree as to the appropriate generic classification, we are in many cases, for the same taxon, listing more than one name as being potentially correct, i.e., as expressing possible generic placements.Our initial approach was to establish a purely nomenclatural inventory, with cross-links between entries of homotypic names. However, we established two levels with different coverage. For all taxa falling within the unit that we call http://www.ipni.org) provided an ideal starting point and first basis for our inventory. Our task then consisted in a literature search for additional names, verification of the source of each and every entry found in IPNI, and nomenclatural (plus ultimately taxonomic) assessment of all names. Especially with respect to taxonomic assessment we made frequent use of the excellent facilities now provided by the Catalogue of Life dynamic checklist . By the way of feedback, our inventory will hopefully be used to improve the completeness and accuracy of the data in both IPNI and CoL.The International Plant Name Index clade is here included.Microparacaryum and Bothriospermum, even though close to Cynoglossum sensu lato according to DNA-based phylogeny, are considered sufficiently distinct to be left outside. The same applies to the not yet sequenced Brandella, a likely synonym of Microparacaryum.Conversely, the genera Cynoglossum but, according not only to sequence data, but at least to some extent morphology, do not belong here. One comprises the indigenous New-World \u201cCynoglossum\u201d species, the second a group of mainly African species, some of which had been erroneously placed in Paracynoglossum. These groups are here considered as non-Cynoglossum and must await their description as separate genera to be correctly placed. A similar case is that of Afrotysonia, a small African genus morphologically very close to Cynoglossum, but which on account of recent, unpublished sequence data is akin to the afore-mentioned African group.Finally, there are two groups of species, or clades, that have not so far been challenged as members of Cynoglossum sensu lato appears in green type, and that for a non- Cynoglossum taxon, in orange type. Furthermore a taxonomic distinction is made: for names that are potentially acceptable under either Cynoglossum in the wide sense or one of its constituent segregate genera the headline is set in bold-face type; for those of non- Cynoglossum taxa that are currently accepted it also appears in bold-face print; for all other names (whether legitimate or illegitimate) that we consider as synonyms under any currently acceptable option the headline is left in normal type.To make the above taxonomic distinction immediately clear for the reader, in the inventory the headline with a name of a taxon belonging to Cynoglossum sensu lato, at least with respect to their nomenclatural type (mentioned in parenthesis) is as follows :The list of names of genera belonging in Adelocaryum Brand (A.coelestinum (Lindl.) Brand, Cynoglossumcoelestinum Lindl.)Anchusopsis Bisch. (A.longiflora (DC.) Bisch., Cynoglossumlongiflorum Benth. (non Lehm.), Omphalodeslongiflora DC. [= C.grandiflorum Benth.] (\u2261 Lindelofia Lehm.)Bilegnum Brand (B.bungei (Boiss.) Brand, Mattiabungei Boiss., Cynoglossumbungei (Boiss.) Greuter & Stier)Cerinthopsis Kotschy ex Paine Greuter & Burdet)Cynoglossum L. Cyphomattia Boiss. (C.lanata (Lam.) Boiss., Cynoglossumlanatum Lam.)Kuschakewiczia Regel & Smirn. Greuter & Stier)Lindelofia Lehm. , Omphalodeslongiflora DC., L.longiflora (DC.) Baill.) [= C.grandiflorum Benth.]Mattia Schult., nom. illeg. Greuter & Burdet)Mattia Roem. & Schult., nom. illeg. (non Mattia Schult.) (Paracaryumaucheri (A. DC.) Boiss., M.aucheri A. DC., Mattiastrumaucheri (A. DC.) Brand, Cynoglossumaucheri (A. DC.) Greuter & Burdet)Mattiastrum (Boiss.) Brand (Paracaryumsect.Mattiastrum Boiss.) (type not designated)Paracaryopsis (Riedl) R. R. Mill R. R. Mill, A.coelestinum (Lindl.) Brand)Paracaryum (A. DC.) Boiss. Boiss., Cynoglossumrugulosum (DC.) Greuter & Burdet)Paracynoglossum Popov (P.denticulatum (A. DC.) Popov, Cynoglossumdenticulatum A. DC.)Pardoglossum Barbier & Mathez (P.atlanticum (Pit.) Barbier & Mathez, Solenanthusatlanticus Pit., Cynoglossumpitardianum Greuter & Burdet)Rindera Pall. Greuter & Burdet)Solenanthus Ledeb. Greuter & Burdet)Trachelanthus Kunze (T.cerinthoides (Boiss.) Kunze, Solenanthuscerinthoides Boiss., Cynoglossumcerinthoides (Boiss.) Greuter & BurdetCynoglossum sensu lato. However, each of them (except Afrotysonia) once included taxa that are currently placed, or still includes taxa that were at one time placed, in a genus belonging to Cynoglossum sensu lato :None of the following genera, with respect to their nomenclatural type (mentioned in parenthesis), is assigned by us to Afrotysonia Rauschert (A.africana (Bolus) Rauschert, Tysoniaafricana Bolus)Anchusa L. Antiotrema Hand.-Mazz. (A.dunnianum (Diels) Hand.-Mazz., Cynoglossumdunnianum Diels)Austrocynoglossum Popov ex R. R. Mill (A.latifolium (R. Br.) R. R. Mill, Cynoglossumlatifolium R. Br.)Bothriospermum Bunge (B.chinense Bunge)Brandella R. R. Mill (B.erythraea (Brand) R. R. Mill, Adelocaryumerythraeum Brand, Cynoglossumerythraeum (Brand) Riedl) [= Microparacaryum]Cynoglossopsis Brand (C.latifolia (Hochst. ex A. Rich.) Brand, Echinospermumlatifolium Hochst. ex A. Rich., Cynoglossumhochstetteri Vatke)Cynoglossospermum Siegesb. ex Kuntze, nom. illeg. (\u2261 Lappula Moench) (C.lappula (L.) Kuntze, Myosotislappula L.) [= L.squarrosa (Retz.) Dumort.]Echinospermum Lehm., nom. illeg. (\u2261 Lappula Moench) (E.lappula (L.) Lehm., Myosotislappula L.) [= L.squarrosa (Retz.) Dumort.]Echium L. (E.vulgare L.)Eritrichium Schrad. ex Gaudin (E.nanum (Vill.) Schrad. ex Gaudin, Myosotisnana Vill.)Hackelia Opiz (H.deflexa (Wahlenb.) Opiz, Myosotisdeflexa Wahlenb., Cynoglossumdeflexum (Wahlenb.) Roth)Lappula Moench Scop.) [= L.squarrosa (Retz.) Dumort.]Lepechiniella Popov [type not designated]Lobostemon Lehm. (L.echioides Lehm.)Microparacaryum (Popov ex Riedl) Hilger & Podlech (Paracaryumsect.Microparacaryum Popov ex Riedl) (P.intermedium (Fresen.) Lipsky, Cynoglossumintermedium Fresen., M.intermedium (Fresen.) Hilger & PodlechMoltkia Lehm. (M.coerulea (Willd.) Lehm., Onosmacoerulea Willd.)Myosotidium Hook. (M.nobile (Hook. f.) Hook., Cynoglossumnobile Hook. f.) [M.hortensia (Decne.) Baill.]Myosotis L. (M.scorpioides L.)Omphalium Roth s. prop. , OmphaliOmphalodes Mill. Voss, nom. rej. prop., Oncaglossum Sutor\u00fd (O. pringlei (Greenm.) Sutor\u00fd, Cynoglossumpringlei Greenm.)Onosma L. (O.echioides L.)Oreocarya Greene (O.suffruticosa (Torrey) Greene, Myosotissuffruticosa Torrey)Pectocarya DC. ex Meisn. (P.lateriflora (Lam.) DC., Cynoglossumlateriflorum Lam.)Picotia Roem. & Schult., nom. illeg. Voss, nom. rej. prop.Pseudomertensia Riedl Lindl., nom. rej.) (P.elongata (Decne.) Riedl, L.elongatum Decne.)Rochelia Rchb., nom. cons. Wettst.)Selkirkia Hemsl. (S.berteroi (Colla) Hemsl. (Cynoglossumberteroi Colla)Suchtelenia Kar. ex Meisn. A. DC.)Symphytum L. Tysonia Bolus, nom. illeg. (non Tysonia Fontaine) (\u2261 Afrotysonia Rauschert) Rauschert)grey type. No attempt at a complete coverage of such designations has been made. By and large, only those have been retained that have been registered in IPNI, the purpose being to document their actual status of non-names. Most often, they are junior isonyms without nomenclatural status of their own; or in some cases, phantom entries of names not appearing at all in their alleged place of publication. Several were deliberately proposed as new but failed to meet the requirements for valid publication; they were sometimes validly published subsequently \u2013 perhaps unnoticed by others, including ourselves, in which case they will have to be added in the future, with their proper source.Designations resembling names but that have not been validly published, being no names in the sense of the ICN , have noCynoglossum sensu lato are shown in the electronic appendices Suppl. materials The contents of the nomenclatural database for bold-face or normal) used in the headline are those explained above and show taxonomic placement, acceptability, and nomenclatural status (or absence thereof). With minor exceptions, all places of publication cited here have been verified by us. Abbreviation of name authors and publication titles follows the standards of IPNI. Correctable orthographical errors, when they appear in the original publication, are cited parenthetically between single quotes.1. Headline (mandatory), showing the name with author citation and reference to the place and year of valid publication. Colour and type : a direct copy of the current (November 2014) entry in the International Plant Name Index, underlain by a link to the entry itself (which may and hopefully in many cases will have been modified since that date). When IPNI shows more than one entry, a choice has been made as follows: When a recent entry without stated source exists, it is preferred; otherwise, when the type or original material of the name is from the Americas the Gray Card Index (GCI) entry has been selected; when it is from Australia, the Australian Plant Name Index (APNI) entry shows up; when it is from elsewhere, the Index Kewensis (IK) entry has been chosen; in case of more than one entry from the same source, the more recent, more accurate or more complete was given preference. Names not listed in IPNI at all are marked \u201cabsent\u201d.Cynoglossum sensu lato being treated as a single genus. The name in the headline is either declared \u201caccepted\u201d or referred to the name considered as correct, if it exists; if none exists , the existing combination is used but with \u201cCynoglossum\u201d placed between quotation marks. Names in the rank of variety or below are not normally accepted but assigned to a species or subspecies. In case of heterotypic synonymy, i.e., when the accepted name has a type different from that of the name in the headline, the former is placed between square brackets. Names appearing in the ASSESSMENT field are cross-linked to their own entry. Names that are not validly published remain unassessed, as they have no type hence no taxonomic identity.3. Field ASSESSMENT : In this field, each name is taxonomically referred to the name considered as correct under the option of sect. nov., spec. nov., var. nov. \u2013 or taxon nov.). A legitimate name with a basionym, which results from transfer of a former name to a new rank (both ranks being mentioned) and/or from its use in a new combination, is termed comb. nov., stat. nov., comb. & stat. nov., comb. in stat. nov., as the case may be. A replacement name, based on a replaced synonym, is designated as nom. nov. An illegitimate name (nom. illeg.) is qualified as nomenclaturally superfluous [superfl.] and/or as a junior homonym [homonym] to show the cause of illegitimacy. A name or designation that had been validly published earlier than in the place cited in the headline is termed isonym; when it was not validly published in that place, as inval. [with mention of the requirements it failed to comply with]; and when it does not appear there at all, as no name4. Field STATUS (mandatory): The nomenclatural status of each name is indicated as follows. A legitimate name published as a name of a new taxon is defined by its rank, if any , to which limited free access is granted to individual scientists, or to items offered by journal or book publishers only upon subscription or against payment of a fee, are also provided \u2013 but only to the generally accessible level .For protologues in publications not (not yet) available online, ad-hoc scans (\u201cclippings\u201d in pdf format) were uploaded to the Biodiversity Literature Repository (https://zenodo.org/collection/user-biosyslit). This solution potentially makes all the treatments of all the taxa citable and the digital representation directly accessible, while not violating the copyright, if any, of the publication (https://www.datacite.org/) allow the treatments to be easily cited and retrieved using a familiar, standard, and persistent identifier, and discoverable through search tools such as Refindit (http://refindit.org).5. Field REFERENCE : In this field a link to the protologue is included whenever that text is freely available online. Open-access sources are preferred whenever they exist. Links to journals available through JSTOR (lication . BLR pro6. Field SYNONYMY (not mandatory): Synonymy is given once for every group of names based on the same type. The synonyms, chronologically arranged, appear either in the entry of the accepted name, or its basionym if it has one, or a replaced synonym if that is older. For each entry with one or more homotypic synonyms, a clickable cross-link to the entry including the synonymy is provided in the field BASIS, under \u201cbasionym\u201d or \u201creplaced synonym\u201d. Names appearing in a SYNONYMY field are cross-linked to their own entry. For technical reasons, heterotypic synonyms (if any) are not included in these synonymies; they can be found with the help of the taxonomic equivalences given in the ASSESSMENT field in square brackets, when appropriate.Originalmaterial, comprising the verbatim citation [from protologue] of any indication, in the protologue itself, relevant for establishing what elements have been used by the author of the validating description or diagnosis; when no original material is mentioned in the protologue, this citation is replaced by an explanatory statement. Thereafter, whenever possible, concrete type specimens , or original specimens or illustrations, are enumerated, with their herbarium of deposit and accession number, followed by an asterisk (*) when a digital image of the specimen can be consulted online via the Internet. Whenever traced, places of lectotype designation are mentioned. \u2013 For new combinations, names at new rank and replacement names, the BASIS field mentions the basionym and/or replaced synonym, cross-linked to their own entry. \u2013 Names that are not validly published lack a nomenclatural basis.7. Field BASIS : For names of new taxa, this field includes information on the nomenclatural type, or relevant for its establishment if it has not been designated so far. It starts with the indication of 8. Field COMMENTS : Free text in which any particular circumstances related to the listed name are mentioned, e.g. those relevant for their status, adopted spelling and authorship, taxonomic assessment and typification, in particular in (but not limited to) those cases in which our conclusions differ from those currently prevailing in the literature and/or indexes.http://www.ipni.org). However, it soon appeared that IPNI is neither complete nor consistently accurate \u2013 which is not really a surprise but does not detract from the general usefulness and value of IPNI as a first-rate means of information on names and nomenclatural data. Yet, IPNI\u2019s shortcomings must be mentioned here as a positive fact, as they were our initial trigger. They encouraged us to embark on our self-set task: to complete and refine the inventory of names relevant in the taxonomic context of Cynoglossum sensu lato. Had we guessed beforehand the amount of work involved we might well have desisted, but when it dawned upon us it was too late to back out.As mentioned before, our main initial source of names was the International Plant Name Index was in sight.http://www.worldcat.org) and the Karlsruhe Virtual Catalogue for books, and for journals the German Zeitschriftendatenbank , are invaluable tools, registering both physical publications with their location and virtual, digitised media with their access links. Other directories, concerned with online-accessible publications only, were also regularly consulted, in particular Biological Heritage Library , Botanicus (http://www.botanicus.org/), Biblioteca digital del Real Jard\u00edn Bot\u00e1nico [Madrid] , Gallica, biblioth\u00e8que num\u00e9rique de la Biblioth\u00e8que Nationale de France , Europeana (http://www.europeana.eu/), and several others. During the implementation of our plans, when tracking down every reference found within and outside the IPNI dataset, we were greatly assisted by the modern search mechanisms now available online. Literature directories such as WorldCat (http://plants.jstor.org), which unfortunately is not accessible for free. Other important (and free) sources of images are institute-based and must be accessed individually, as there is no global portal to that information yet. Many important herbarium holdings are presently accessible online, at least in part, including Virtual Herbaria , Mus\u00e9um national d\u2019histoire naturelle , Botanical Museum Berlin-Dahlem , Conservatoire botanique de la Ville de Gen\u00e8ve , Linnean Society of London , Botany Portal of Field Museum , Harvard University Herbaria , Smithsonian Institution Washington , Herbarium Centrale Italicum, Museo di Storia Naturale dell'Universit\u00e0 die Firenze etc.The ever increasing presence in the Internet of digitised images of herbarium specimens, particularly types, has enabled us to add a feature to our data that would have been unthinkable a few years back: direct reference to type specimens and elements of the original material, usually with herbarium location and accession numbers, plus an indication by means of an asterisk (*) that an image has been consulted by us. The most complete and useful gateway to type specimen illustrations is JSTOR\u2019s Global Plants . While less complete than IPNI as an inventory of names, it has one quality that is absent from the latter: it advises on synonymy. During the last stage of editing our inventory, when we introduced taxonomic assessment of names into it, we have repeatedly consulted CoL\u2019s dynamic checklist and found it a useful and usually, though not invariably, accurate guide in matters of taxonomic synonymy. Especially when the correct identity of non-Cynoglossum names had to be assessed, we mostly found ourselves in full agreement with the choices in CoL.Finally, mention must be made of Species 2000 and ITIS\u2019 Catalogue of Life of names not validly published in the place cited ; 268 (in orange) of names of which the types do not belong to our core or target group but have been nomenclaturally or taxonomically associated with it in the past, in some way or other; and 861 (in green) that do really pertain. The statistical digest in Table The nomenclatural database for From the very beginning, one of our self-set targets was a comparison of the information found by us with what is currently in the IPNI database. We wanted, for one, to get an idea of how reliable IPNI is and to which extent, and in which respect, it might be inaccurate and/or incomplete. Also, we had and keep the hope that, subsequent to their publication, our data will be of use for updating the IPNI record, as we know and appreciate the hard work of the IPNI staff, both at Kew and Harvard, to continually improve their entries.Index Kewensis volumes were scanned; nor on the failure to adopt IPNI\u2019s own standards in many of the old entries, as we know that standardising them is among the ongoing concerns of the IPNI staff. Apart from such minor, trivial aspects, we found that IPNI currently has shortcomings principally in three fields.We will not dwell on minor errors, including wrong numbers, some of which may well go back to weaknesses of the optical character recognition (OCR) software used when the original Index Kewensis, from which the bulk of IPNI entries originates, did not cover these ranks (contrary to the Gray Card Index). Only in recent years have infraspecific names and those of subdivisions of genera been registered consistently, and if it is judged worth while to fill that gap retroactively, this will constitute a gigantic task that will take decades to complete. Currently, for infraspecific names in particular, information in IPNI is fragmentary only. On the other hand, at the level of genera (94.4 %) and species (95.8 %) the coverage is reasonably good.1. Missing names. These are in their great majority found in ranks between genus and species and below species, which is explained by the fact that Index Kewensis are full of records of what appear to be junior homonyms, but are in fact mere misapplications of earlier names \u2013 a distinction that, while nomenclaturally relevant now, was not made at that time. This ballast, of what in terms of current nomenclature are junior isonyms without standing, lost whatever relevance it may once have had when it was decided to eliminate from the IPNI database the original reason of being of such entries: the sense in which the names had been misapplied, carefully recorded in Index Kewensis. As they are listed now, devoid of their rationale, all these isonyms are just only confusing, and a real nuisance. We hope that sooner or later they will be thrown over board.2. Inclusion of non-names. In a nomenclatural database, designations that are not validly published should be either eliminated or \u2013 if maintained to avoid loss of information \u2013 prominently flagged. Current IPNI policy is to record them when they are intended as a nomenclatural novelty, but the author fails to comply with the conditions for valid publication, a fact that is then duly noted. But of old, such \u201cnames\u201d were accepted at face value, and if and when validation finally occurred no note was taken. Worse, the early volumes of Index Kewensis did not cite basionyms nor mention parenthetical authors, and illegitimacy at that time was an unheard-of concept. Updating such imperfect information is a big, demanding task for the future, requiring verification of the original source if it is to be properly done; we hope that the present inventory will be used for that purpose. Verification of author citations is a particular aspect of status assessment and is also necessary for former entries, because the relevant rules have changed substantially after the Tokyo Congress in 1993.3. Wrong assessment of the status of names, wrong author citations. For newly added names, IPNI is careful to distinguish legitimate from illegitimate ones, and new combinations or replacement names are referred to their basionym or replaced synonym \u2013 additionally, with increasing frequence, they are linked to outside sources available online. Old entries, however, have been updated only in part. The early volumes of The problems just highlighted with respect to IPNI, the main existing nomenclatural data source for vascular plants, strengthen our belief in the usefulness of improved nomenclatural inventories such as the present one. We are conscious of the fact that no such list will ever be perfect, but we also believe that, beyond a certain point, aiming at an ever greater level of reliability becomes a futile exercise, an investment of time and money for little if any useful return. Once an inventory of this kind exists, it should be possible to confer official sanction to its basic contents, meaning certain parameters of the listed names . We strongly advocate the creation of such a stabilising option under the rules governing nomenclature.Cynoglossum sensu lato. This is no disadvantage. On the contrary, it permits us to present our readers with a dual approach, allowing them to choose between alternative classifications.As stated in the introduction, the authors of this paper are divided as to their preferred generic concept for The problem with narrowly defined genera, the option endorsed by HHH, is that it would be premature to present them in a firm classificatory frame. Traditional generic definitions, based mainly on fruit morphology, are clearly unnatural in some cases. A reassessment leading to the establishment of natural segregate units requires further in-depth morphological and expanded molecular studies. The solution presented here \u2013 the best that is currently feasible \u2013 is to declare as acceptable, or potentially correct, names that exist under any of the currently adopted genera. This does not of course preclude the treatment of some names as synonyms when they belong to a taxon (species or subspecies) for which an older name exists, but for the time being it prevents the validation of new, potentially correct combinations in cases when they are likely needed under the segregate-genera concept.Cynoglossum sensu lato as a single genus, favoured by WG and VS, is less prone to future change. It is certainly possible, indeed likely, that some species currently assigned to that genus will have to be excluded from it in the future, but in general terms the unit that has emerged as monophyletic Greuter & Stier, comb. nov. \u2261 Rinderaalaica Lazkov in Bot. Zhurn. (Moskva & Leningrad) 85(8): 116. 2000. (IPNI urn:lsid:ipni.org:names:77146588-1)Cynoglossumalbiflorum (Czukav. & Meling) Greuter & Stier, comb. nov. \u2261 Solenanthusalbiflorus Czukav. & Meling in Novosti Sist. Vyssh. Rast. 19: 161. 1982. (IPNI urn:lsid:ipni.org:names:77146589-1)Cynoglossumanchusoides subsp. asperum (Rech. f.) Greuter & Stier, comb. nov. \u2261 Lindelofiaaspera Rech. f. in Ann. Naturhist. Mus. Wien 58: 48. 1951 \u2261 Lindelofiaanchusoidessubsp.aspera (Rech. f.) Sadat in Mitt. Bot. Staatssamml. M\u00fcnchen 28: 104. 1989. (IPNI urn:lsid:ipni.org:names:77146590-1)Cynoglossumasperum (Stocks) Greuter & Stier, comb. nov. \u2261 Paracaryumasperum Stocks in Hooker\u2019s J. Bot. Kew Gard. Misc. 4: 175. 1852. (IPNI urn:lsid:ipni.org:names:77146591-1)Cynoglossumaustroechinatum (Popov) Greuter & Stier, comb. nov. \u2261 Rinderaaustroechinata Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 222. 1950. (IPNI urn:lsid:ipni.org:names:77146592-1)Cynoglossumbadghysii (Sadat) Greuter & Stier, comb. nov. \u2261 Mattiastrumbadghysii Sadat in Mitt. Bot. Staatssamml. M\u00fcnchen 28: 67. 1989. (IPNI urn:lsid:ipni.org:names:77146593-1)Cynoglossumbakhtiaricum (Khat.) Greuter & Stier, comb. nov. \u2261Solenanthusbakhtiaricus Khat. in Iranian J. Bot. 8: 6. 1999. (IPNI urn:lsid:ipni.org:names:77146594-1)Cynoglossumbrachystemon (Fisch. & C. A. Mey.) Greuter & Stier, comb. nov. \u2261Solenanthusbrachystemon Fisch. & C. A. Mey. in Bull. Soc. Imp. Naturalistes Moscou 11: 306. 1838. (IPNI urn:lsid:ipni.org:names:77146595-1)Cynoglossumbungei (Boiss.) Greuter & Stier, comb. nov. \u2261Mattiabungei Boiss., Fl. Orient. 4: 274. 1875. (IPNI urn:lsid:ipni.org:names:77146596-1)Cynoglossumcampanulatum (Riedl) Greuter & Stier, comb. nov. \u2261Lindelofiacampanulata Riedl in Biol. Skr. 13: 198. 1963. (IPNI urn:lsid:ipni.org:names:77146597-1)Cynoglossumcoechinatum (Popov) Greuter & Stier, comb. nov. \u2261Rinderacoechinata Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 223. 1950. (IPNI urn:lsid:ipni.org:names:77146598-1)Cynoglossumcrista-galli (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261Mattiastrumcrista-galli Rech. f. & Riedl in Biol. Skr. 13: 207. 1963. (IPNI urn:lsid:ipni.org:names:77146599-1)Cynoglossumcristulatum (Lipsky) Greuter & Stier, comb. nov. \u2261Rinderacristulata Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 26: 570. 1910. (IPNI urn:lsid:ipni.org:names:77146600-1)Cynoglossumcyclhymenium (Boiss.) Greuter & Stier, comb. nov. \u2261Paracaryumrugulosumvar.cyclhymenium Boiss., Fl. Orient. 4: 256. 1875 \u2261 Paracaryumcyclhymenium (Boiss.) Riedl in Rechinger, Fl. Iranica 48: 102. 1967. (IPNI urn:lsid:ipni.org:names:77146602-1)Cynoglossumcynoglossoides (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261Mattiastrumcynoglossoides Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 123. 1967. (IPNI urn:lsid:ipni.org:names:77146603-1)Cynoglossumdensum (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261Mattiastrumdensum Rech. f. & Riedl in Oesterr. Bot. Z. 110: 519. 1963. (IPNI urn:lsid:ipni.org:names:77146604-1)Cynoglossumdielsii (Bornm.) Greuter & Stier, comb. nov. \u2261 Mattiastrumdielsii Bornm. in Bot. Jahrb. Syst. 66: 236. 1934. (IPNI urn:lsid:ipni.org:names:77146607-1)Cynoglossumdieterlei (Sadat) Greuter & Stier, comb. nov. \u2261 Mattiastrumdieterlei Sadat in Mitt. Bot. Staatssamml. M\u00fcnchen 28: 88. 1989. (IPNI urn:lsid:ipni.org:names:77146611-1)Cynoglossumdubium (Fisch. & C. A. Mey.) Greuter & Stier, comb. nov. \u2261 Solenanthusdubius Fisch. & C. A. Mey. in Bull. Soc. Imp. Naturalistes Moscou 11: 306. 1838. (IPNI urn:lsid:ipni.org:names:77146616-1)Cynoglossumdumanii (Ayta\u00e7 & R. R. Mill) Greuter & Stier, comb. nov. \u2261 Rinderadumanii Ayta\u00e7 & R. R. Mill in Edinburgh J. Bot. 61: 113. 2005. (IPNI urn:lsid:ipni.org:names:77146617-1)Cynoglossumeriocalycinum (Boiss. & Buhse) Greuter & Stier, comb. nov. \u2261 Solenanthuseriocalycinus Boiss. & Buhse in Nouv. M\u00e9m. Soc. Imp. Naturalistes Moscou 12: 156. 1860. (IPNI urn:lsid:ipni.org:names:77146618-1)Cynoglossumferganicum (Popov) Greuter & Stier, comb. nov. \u2261Rinderaferganica Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 219. 1950. (IPNI urn:lsid:ipni.org:names:77146619-1)Cynoglossumflaviflorum (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261Mattiastrumflaviflorum Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 122. 1967. (IPNI urn:lsid:ipni.org:names:77146620-1)Cynoglossumfornicatum (Pazij) Greuter & Stier, comb. nov. \u2261Rinderafornicata Pazij in Bot. Mater. Gerb. Inst. Bot. Akad. Nauk Uzbeksk. S.S.R. 15: 24. 1959. (IPNI urn:lsid:ipni.org:names:77146621-1)Cynoglossumglabratum (Pazij) Greuter & Stier, comb. nov. \u2261Rinderaglabrata Pazij in Bot. Mater. Gerb. Inst. Bot. Akad. Nauk Uzbeksk. S.S.R. 15: 26. 1959. (IPNI urn:lsid:ipni.org:names:77146622-1)Cynoglossumglandulosum (Khat.) Greuter & Stier, comb. nov. \u2261Paracaryumglandulosum Khat. in Iranian J. Bot. 6: 228. 1994. (IPNI urn:lsid:ipni.org:names:77146623-1)Cynoglossumhedgei (Ayta\u00e7 & R. R. Mill) Greuter & Stier, comb. nov. \u2261Paracaryumhedgei Ayta\u00e7 & R. R. Mill in Edinburgh J. Bot. 61: 109. 2005. (IPNI urn:lsid:ipni.org:names:77146624-1)Cynoglossumheratense (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261Mattiastrumheratense Rech. f. & Riedl in Biol. Skr. 13: 210. 1963. (IPNI urn:lsid:ipni.org:names:77146625-1)Cynoglossumhimalayense (Klotzsch) Greuter & Stier, comb. nov. \u2261Mattiahimalayensis Klotzsch in Klotzsch & Garcke, Bot. Ergebn. Reise Waldemar: 94. 1862. (IPNI urn:lsid:ipni.org:names:77146627-1)Cynoglossumhissaricum (Lipsky) Greuter & Stier, comb. nov. \u2261Trachelanthushissaricus Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 23: 202. 1904. (IPNI urn:lsid:ipni.org:names:77146629-1)Cynoglossumholochiton (Popov) Greuter & Stier, comb. nov. \u2261 Rinderaholochiton Popov in Komarov, Fl. SSSR 19: 716. 1953. (IPNI urn:lsid:ipni.org:names:77146631-1)Cynoglossumhupehense (R. R. Mill) Greuter & Stier, comb. nov. \u2261 Solenanthushupehensis R. R. Mill in Notes Roy. Bot. Gard. Edinburgh 44: 271. 1987. (IPNI urn:lsid:ipni.org:names:77146633-1)Cynoglossumhystrix Greuter & Stier, nom. nov. \u2261 Rinderaechinata Regel in Bull. Soc. Imp. Naturalistes Moscou 41(1): 92. 1868 (non Cynoglossumechinatum Thunb.). (IPNI urn:lsid:ipni.org:names:77146637-1)Cynoglossumindecorum Greuter & Stier, nom. nov. \u2261 Solenanthusmicranthus Riedl in Ann. Naturhist. Mus. Wien 76: 635. 1972 (non Cynoglossummicranthum Poir.). (IPNI urn:lsid:ipni.org:names:77146640-1)Cynoglossumintegerrimum (P. Myrzakulov) Greuter & Stier, comb. nov. \u2261 Paracaryumintegerrimum P. Myrzakulov in Bot. Mater. Gerb. Bot. Inst. Bot. Acad. Nauk Kazakhsk. S.S.R. 9: 30. 1975. (IPNI urn:lsid:ipni.org:names:77146641-1)Cynoglossumkarakoricum (Podlech & Sadat) Greuter & Stier, comb. nov. \u2261 Mattiastrumkarakoricum Podlech & Sadat in Mitt. Bot. Staatssamml. M\u00fcnchen 27: 65. 1988. (IPNI urn:lsid:ipni.org:names:77146647-1)Cynoglossumkarataviense (Pavlov ex Popov) Greuter & Stier, comb. nov. \u2261 Paracaryumkarataviense Pavlov ex Popov in Komarov, Fl. URSS 19: 715. 1953. (IPNI urn:lsid:ipni.org:names:77146648-1)Cynoglossumkarateginum (Lipsky) Greuter & Stier, comb. nov. \u2261 Solenanthuskarateginus Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 23: 196. 1904. (IPNI urn:lsid:ipni.org:names:77146649-1)Cynoglossumkhorassanicum (Khat.) Greuter & Stier, comb. nov. \u2261 Paracaryumkhorassanicum Khat. in Iranian J. Bot. 8: 4. 1999. (IPNI urn:lsid:ipni.org:names:77146650-1)Cynoglossumkokanicum (Regel) Greuter & Stier, comb. nov. \u2261 Solenanthuskokanicus Regel in Izv. Imp. Obshch. Lyubit. Estestv. Moskovsk. Univ. 34(2) [Putesh. Turkest. 3(18)]: 60 (\u2018olgae\u2019), 89. 1882. (IPNI urn:lsid:ipni.org:names:77146651-1)Cynoglossumkorolkowii (Lipsky) Greuter & Stier, comb. nov. \u2261 Trachelanthuskorolkowii Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 23: 199. 1904. (IPNI urn:lsid:ipni.org:names:77146652-1)Cynoglossumkorshinskyi (Lipsky) Greuter & Stier, comb. nov. \u2261 Cyphomattiakorshinskyi Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 26: 511. 1910. (IPNI urn:lsid:ipni.org:names:77146653-1)Cynoglossumkrasniqii Wraber, spec. nov. \u2013 Descr.: Wraber in Candollea 41: 145. 1986. \u2013 Holotype: Srbija, Kosovo: Pa\u0161trik supra vicum Goro\u017eup prope oppidum Prizren, 1520 m s.m., 30.4.1983 (flor.), T. Wraber (BEO). (IPNI urn:lsid:ipni.org:names:77146654-1)Cynoglossumkuhitangicum (Raenko) Greuter & Stier, comb. nov. \u2261 Rinderakuhitangica Raenko in Novosti Sist. Vyssh. Rast. 34: 151. 2002. (IPNI urn:lsid:ipni.org:names:77146655-1)Cynoglossumkuramense (Turak.) Greuter & Stier, comb. nov. \u2261 Rinderakuramensis Turak. in Novosti Sist. Vyssh. Rast. 28: 131. 1991. (IPNI urn:lsid:ipni.org:names:77146656-1)Cynoglossumlambertianum (C. B. Clarke) Greuter & Stier, comb. nov. \u2261 Paracaryumlambertianum C. B. Clarke in Hooker, Fl. Brit. India 4: 161. 1883. (IPNI urn:lsid:ipni.org:names:77146657-1)Cynoglossumlongifolium (Leichtlin ex Beck & F. Abel) Greuter & Stier, comb. nov. \u2261 Lindelofialongifolia Leichtlin ex Beck & F. Abel in Wiener Ill. Gart.-Zeitung 13: 326. 1888. (IPNI urn:lsid:ipni.org:names:77146658-1)Cynoglossumlongipedicellatum (Riedl) Greuter & Stier, comb. nov. \u2261 Lindelofialongipedicellata Riedl in Biol. Skr. 13: 199. 1963. (IPNI urn:lsid:ipni.org:names:77146659-1)Cynoglossumluristanicum (N\u00e1b\u011blek) Greuter & Stier, comb. nov. \u2261 Paracaryumluristanicum N\u00e1b\u011blek in Spisy P\u0159\u00edr. Fak. Masarykovy Univ. 70: 23. 1926. (IPNI urn:lsid:ipni.org:names:77146660-1)Cynoglossummedium (Turrill) Greuter & Stier, comb. nov. \u2261 Bilegnummedium Turrill in Bull. Misc. Inform. Kew 1929: 232. 1929. (IPNI urn:lsid:ipni.org:names:77146661-1)Cynoglossumminimum (Brand) Greuter & Stier, comb. nov. \u2261 Solenanthusminimus Brand in Repert. Spec. Nov. Regni Veg. 13: 547. 1915. (IPNI urn:lsid:ipni.org:names:77146662-1)Cynoglossumminutiflorum Greuter & Stier, nom. nov. \u2261 Lindelofiamicrantha Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 139. 1967 (non Cynoglossummicranthum Poir.). (IPNI urn:lsid:ipni.org:names:77146663-1)Cynoglossummodestum (Boiss. & Hausskn.) Greuter & Stier, comb. nov. \u2261 Paracaryummodestum Boiss. & Hausskn. in Boissier, Pl. Or. Nov. Dec. 2: 5. 1875. (IPNI urn:lsid:ipni.org:names:77146664-1)Cynoglossummulticaule (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261 Mattiastrummulticaule Rech. f. & Riedl in Biol. Skr. 13: 216. 1963. (IPNI urn:lsid:ipni.org:names:77146665-1)Cynoglossumnebulicola (R. R. Mill) Greuter & Stier, comb. nov. \u2261 Adelocaryumnebulicola R. R. Mill in Edinburgh J. Bot. 67: 148. 2010. (IPNI urn:lsid:ipni.org:names:77146666-1)Cynoglossumneubaueri (Rech. f.) Greuter & Stier, comb. nov. \u2261 Moltkianeubaueri Rech. f. in Ann. Naturhist. Mus. Wien 58: 57. 1951. (IPNI urn:lsid:ipni.org:names:77146667-1)Cynoglossumnigrum (Riedl) Greuter & Stier, comb. nov. \u2261 Mattiastrumnigrum Riedl in Rechinger, Fl. Iranica 48: 118. 1967. (IPNI urn:lsid:ipni.org:names:77146668-1)Cynoglossumoblongifolium (Popov) Greuter & Stier, comb. nov. \u2261 Rinderaoblongifolia Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 224. 1950. (IPNI urn:lsid:ipni.org:names:77146669-1)Cynoglossumochroleucum (Kar. & Kir.) Greuter & Stier, comb. nov. \u2261 Rinderaochroleuca Kar. & Kir. in Bull. Soc. Imp. Naturalistes Moscou 15: 408. 1842. (IPNI urn:lsid:ipni.org:names:77146670-1)Cynoglossumolgae (Regel & Smirn.) Greuter & Stier, comb. nov. \u2261 Solenanthusolgae Regel & Smirn. in Izv. Imp. Obshch. Lyubit. Estestv. Moskovsk. Univ. 34(2) [Putesh. Turkest. 3(18)]: 59. 1882. (IPNI urn:lsid:ipni.org:names:77146671-1)Cynoglossumoschense (Popov) Greuter & Stier, comb. nov. \u2261 Rinderaoschensis Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 220. 1950. (IPNI urn:lsid:ipni.org:names:77146672-1)Cynoglossumpersicum (Boiss.) Greuter & Stier, comb. nov. \u2261 Omphalodespersica Boiss., Diagn. Pl. Orient., ser. 1, 7: 30. 1846. (IPNI urn:lsid:ipni.org:names:77146673-1)Cynoglossumphardycalyx Greuter & Stier, nom. nov. \u2261 Paracaryumplatycalyx Riedl in Oesterr. Bot. Z. 110: 535. 1963 Greuter & Stier). (IPNI urn:lsid:ipni.org:names:77146674-1)Cynoglossumplantaginifolium (Lipsky) Greuter & Stier, comb. nov. \u2261 Solenanthusplantaginifolius Lipsky in Trudy Imp. S.-Peterburgsk. Bot. Sada 23: 198. 1904. (IPNI urn:lsid:ipni.org:names:77146675-1)Cynoglossumplatycalyx (Riedl) Greuter & Stier, comb. nov. \u2261 Lindelofiaplatycalyx Riedl in Biol. Skr. 13: 202. 1963. (IPNI urn:lsid:ipni.org:names:77146676-1)Cynoglossumpolyanthum (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261 Mattiastrumpolyanthum Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 123. 1967. (IPNI urn:lsid:ipni.org:names:77146677-1)Cynoglossumpygmaeum (Rech. f.) Greuter & Stier, comb. nov. \u2261 Mattiastrumpygmaeum Rech. f. in Ann. Naturhist. Mus. Wien 58: 52. 1951. (IPNI urn:lsid:ipni.org:names:77146678-1)Cynoglossumrechingeri Greuter & Stier, nom. nov. \u2261 Mattiastrumformosum Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 119. 1967 (non Cynoglossumformosum (R. R. Mill) Greuter & Burdet). (IPNI urn:lsid:ipni.org:names:77146679-1)Cynoglossumregelii Greuter & Stier, nom. nov. \u2261 Solenanthushirsutus Regel in Izv. Imp. Obshch. Lyubit. Estestv. Moskovsk. Univ. 34(2) [Putesh. Turkest. 3(18)]: 60. 1882 (non Cynoglossumhirsutum Thunb.). (IPNI urn:lsid:ipni.org:names:77146680-1)Cynoglossumregium (S. G. Gmel.) Greuter & Stier, comb. nov. \u2261 Symphytumregium S. G. Gmel., Reise Russland 3: 363, t. 36. f. 1. 1774. (IPNI urn:lsid:ipni.org:names:77146684-1)Cynoglossumsessiliflorum (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261 Mattiastrumsessiliflorum Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 125. 1967. (IPNI urn:lsid:ipni.org:names:77146685-1)Cynoglossumstrictissimum (Brand) Greuter & Stier, comb. nov. \u2261 Solenanthusstrictissimus Brand in Repert. Spec. Nov. Regni Veg. 13: 546. 1915. (IPNI urn:lsid:ipni.org:names:77146686-1)Cynoglossumstylosum subsp. pterocarpum (Rupr.) Greuter & Stier, comb. nov. \u2261 Solenanthusnigricansvar.pterocarpus Rupr. in M\u00e9m. Acad. Imp. Sci. St.-P\u00e9tersbourg, ser. 7, 14: 62. 1869 \u2261 Lindelofiastylosasubsp.pterocarpa (Rupr.) Kamelin in Novon 3: 263. 1993. (IPNI urn:lsid:ipni.org:names:77146687-1)Cynoglossumsubscaposum (Rech. f. & Riedl) Greuter & Stier, comb. nov. \u2261 Mattiastrumsubscaposum Rech. f. & Riedl in Rechinger, Fl. Iranica 48: 120. 1967. (IPNI urn:lsid:ipni.org:names:77146688-1)Cynoglossumtenerum (Bornm.) Greuter & Stier, comb. nov. \u2261 Paracaryumtenerum Bornm. in Beih. Bot. Centralbl., Abt. 2, 33: 175. 1915. (IPNI urn:lsid:ipni.org:names:77146689-1)Cynoglossumtrinervium (Duthie) Greuter & Stier, comb. nov. \u2261 Paracaryumtrinervium Duthie in Bull. Misc. Inform. Kew 1912: 39. 1912. (IPNI urn:lsid:ipni.org:names:77146690-1)Cynoglossumtschotkalense (Popov) Greuter & Stier, comb. nov. \u2261 Rinderatschotkalensis Popov in Bot. Mater. Gerb. Bot. Inst. Komarova Akad. Nauk S.S.S.R. 13: 217. 1950. (IPNI urn:lsid:ipni.org:names:77146691-1)Cynoglossumturcomanicum (Bornm. & Sint.) Greuter & Stier, comb. nov. \u2261 Paracaryumturcomanicum Bornm. & Sint. in Beih. Bot. Centralbl., Abt. 2, 20: 193. 1906. (IPNI urn:lsid:ipni.org:names:77146692-1)Cynoglossumturkestanicum (Regel) Greuter & Stier, comb. nov. \u2261 Kuschakewicziaturkestanica Regel in Trudy Imp. S.-Peterburgsk. Bot. Sada 5: 626. 1877. (IPNI urn:lsid:ipni.org:names:77146693-1)Concerning nomenclatural types, we have as a rule limited ourselves to (a) record lectotype designations that we noted during our searches (well aware of the fact that such a search can never be complete and fully reliable), or (b), when no such designation is known, to provide data on which future specialists may base their choice. In the following exceptional cases, new type designations are being effected here:Cynoglossumofficinale var. corsicum E. Rev. ex Brand \u2013 Lectotype (designated here): Fl. Corsica: Evisa, [6 July] 1885, Reverchon in Baenitz, Herbarium europaeum, FR (FR00360781!).Paracaryum sect. Mattiastrum Boiss. \u2013 Type (designated here): P.aucheri (A. DC.) Boiss. Brand, Cynoglossumaucheri (A. DC.) Greuter & Burdet).Additionally we correct an erroneous name:Microparacaryumintermedium f. stellatum (Riedl) Hilger & Podlech, stat. nov. \u2261 Paracaryumstellatum Riedl in Rechinger, Fl. Iranica 48: 104. 1967 \u2261 Microparacaryumintermediumvar.stellatum (Riedl) Hilger & Podlech in Pl. Syst. Evol. 148: 304. 1985 \u2261 Microparacaryumintermediumf.paracaryoides Hilger & Podlech in Pl. Syst. Evol. 148: 305. 1985 (non Microparacaryumintermediumf.paracaryoides Hilger & Podlech in Pl. Syst. Evol. 148: 303. 1985). (IPNI urn:lsid:ipni.org:names:77146694-1)Supplementary material 1Nomenclatural database for Cynoglossum s.l.Data type: listCynoglossum sensu lato - a structured, fully searchable Hypertext Markup Language (HTML) file with names connected by internal links and, where appropriate, linked to external sources.Brief description: Nomenclatural database for File: oo_42064.htmlHilger, H.H.; Greuter, W.; Stier, V.Supplementary material 2Machine readable nomenclatural database for Cynoglossum s.l.Data type: listCynoglossum sensu lato - a structured text file for import, e.g., in MS Excel.Brief description: Nomenclatural database for File: oo_42065.txtHilger, H.H.; Greuter, W.; Stier, V."} +{"text": "The authors have requested the retraction of their paper because they mistakenly analyzed the wrong backcross lines. This mistake was only recently discovered and they are now in the process of repeating the experiment using the correct Backcross Introgression Lines. The authors apologize for this mistake.The above article, published online on 15 October 2015 in Wiley Online Library (Oryza sativa L.) under drought stress. Ecology and Evolution 5(21):5007\u20135015. doi: 10.1002/ece3.1786.Nie, Y. Y., L. Zhang, Y. H. Wu, H. J. Liu, W. W. Mao, J. Du, et\u00a0al. 2015. Screening of candidate genes and fine mapping of drought tolerance quantitative trait loci on chromosome 4 in rice ("} +{"text": "Reason for Erratum:In the original article 2 of the references were cited incorrectly for the name of Teixeira da Silva, J. A. Below are the correct citations:Plant Cell Tissue Organ Cult. 109, 525\u2013533. doi: 10.1007/s11240-012-0119-8Ahmadi, B., Alizadeh, K., and Teixeira da Silva, J. A. (2012). Enhanced regeneration of haploid plantlets from microspores of Brassica napus L. using bleomycin, PCIB, and phytohormones. Brassica napus L. Plant Cell Tissue Organ Cult. 116, 343\u2013351. doi: 10.1007/s11240-013-0408-xAhmadi, B., Shariatpanahi, M. E., and Teixeira da Silva, J. A. (2014). Efficient induction of microspore embryogenesis using abscisic acid, jasmonic acid and salicylic acid in This error does not change the scientific conclusions of the article in any way.The original article has been updated."} +{"text": "Most of what is known regarding the epidemiology of mortality from heart failure (HF) comes from studies within Western populations with few data available from the Asia-Pacific region where the burden of heart failure is increasing.Individual level data from 543694 participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality from HF were estimated separately for Asians and non-Asians for a quintet of cardiovascular risk factors: systolic blood pressure, diabetes, body mass index, cigarette smoking and total cholesterol. All analyses were stratified by sex and study.During 3,793,229 person years of follow-up there were 614 HF deaths (80% Asian). The positive associations between elevated blood pressure, obesity, and cigarette smoking were consistent for Asians and non-Asians. There was evidence to indicate that diabetes was a weaker risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95% CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction\u2009=\u20090.022. Additional adjustment for covariates did not materially change the overall associations. There was no good evidence to indicate that total cholesterol was a risk factor for HF mortality in either population.Most traditional cardiovascular risk factors including elevated blood pressure, obesity and cigarette smoking appear to operate similarly to increase the risk of death from HF in Asians and non-Asians populations alike. Heart failure (HF) is a complex syndrome with a multifactorial aetiology and is a major cause of death and disability in higher-income countries where it is estimated that 2% of adults are affected . The incOur knowledge regarding the causes of HF has chiefly been derived from studies from the US and EuroAll of the individual studies that participated in APCSC obtained ethics approval from their own ethics approval boards. All participants were aged 18 or over and provided informed consent in accordance with the principles of the Declaration of Helsinki.Details of the APCSC have been described elsewhere ,15. In b2) [In most studies, blood pressure was measured at rest in the seated position using a standard mercury sphygmomanometer . TC was 2) . The dia2) . Cigaret2) .Most studies used database linkage to identify deaths, while others also included scheduled follow-up visits or examined hospital records Information on fatal events was classified according to the Ninth Revision of the International Classification of Diseases (ICD-9). The end point considered in this analysis was fatal HF (ICD-9 428). Data quality of the individual cohorts was centrally checked and, if needed, data were recoded for comparability across studies. Where necessary, further details were sought from the principal investigators of each individual study.2[All analyses used individual participant data, restricted to participants aged \u226520\u00a0years at the time of the baseline survey. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for HF for each risk factor, after adjustment for age. All analyses were stratified by sex and study. For linear associations HRs for a unit increase were derived. BMI and HF exhibited a non-linear relationship so the HRs across quarters were reported. In addition, the HR\u2019s across five sequential categories of BMI were reported: <18.5, 18.5\u201321.9, 22\u201324.9, 25\u201329.9 and \u226530\u00a0kg/m2. The anaA total of 543694 participants from 32 cohorts were included in this analysis Table\u00a0. Due to interaction with history of CVD\u2009=\u20090.024). This may have been a chance finding due to the small number (<100) of events that occurred in those with a history of CVD.Overall, 3,793,229 person years of follow-up data contributed to the analysis of SBP with HF during which time 614 deaths (80% Asian) from HF were recorded. In the Asian cohorts, 56% of HF deaths were from Japan, 42% from China and the remainder from Hong Kong, Taiwan, Japan and Korea. There was a significant and linear positive association between SBP and the risk of mortality from HF (p\u2009=\u20090.0003). Every 10\u00a0mmHg increment in SBP increased the risk by 13% (95% CI: 6-21%) with no evidence that the effect varied by sex (p\u2009=\u20090.28) or region as the reference group the U-shaped relation was more evident greater risk of death from HF compared with those without the condition, with no evidence to suggest that the relationship differed significantly by sex (p\u2009=\u20090.59) or by age (p\u2009=\u20090.21) . A 1\u00a0mmol/L increment in TC was associated with a non-significant reduction in HF mortality with no significant evidence of a regional interaction: HR 0.90 (95% CI: 0.77-1.07); p\u2009=\u20090.059; Figure\u00a0This study comprises the largest amount of prospective data to date on the relationship between major cardiovascular risk factors with HF mortality in populations from the Asia-Pacific region. The key findings from this individual participant data meta-analysis indicate positive and independent relationships between elevated blood pressure, obesity, diabetes and cigarette smoking with death from HF in Asians and non-Asians, but no evidence of an association with TC. With the possible exception for blood pressure, the relationships were consistent in those with and without a history of CVD at study baseline. Overall, these current findings are broadly consistent with those reported from Western population-based studies, including Framingham ,25 and NThat diabetes may also be an independent risk factor for incident HF was first shown by the Framingham study where a clinical history of diabetes was associated with a two-fold increased risk in men and a five-fold increased risk for women . Since tIn the current study, a U-shaped association between BMI and mortality from HF was observed such that individuals who were either underweight or obese were at similarly greater risk of dying from HF compared with those of normal weight. This remained unaffected by adjustment for smoking, which may have operated as a confounder of the association given that smokers tend to be relatively leaner than their non-smoking counterparts. Efforts to reduce the impact of reverse causality by excluding the first two years of follow-up also had little impact on the relationship. Our observation that underweight is a risk factor for mortality from HF is tangentially supported by previous hospital-based studies that have shown patients with chronic HF who are underweight have a lower survival than those of normal weight or who are overweight or obese . The incThe epidemiological literature describing the relationship between TC and mortality from HF is inconsistent; some studies have reported a positive or inverThere are some important limitations of this analysis. The lack of a universal definition of HF, and between study differences in its diagnosis and reporting, may have introduced bias. For example, misdiagnosis of HF as stroke, myocardial infarction or IHD in the early 1990\u2019s has been suggested to account for the observed increase in IHD mortality between 1990\u20131995 in Japan . In the In summary, findings from this current study indicate that several traditional and modifiable cardiovascular risk factors, namely elevated blood pressure, diabetes, obesity and cigarette smoking, are independently associated with mortality from HF for Asian and non-Asian populations alike in a broadly consistent manner.APCSC Executive CommitteeM. Woodward (Chair), X. Fang, D.F. Gu, R. Huxley, Y. Imai, H.C. Kim, T.H. Lam, W.H. Pan, A. Rodgers, I. Suh, H. UeshimaParticipating Studies and Principal Collaborators in APCSCAito Town: A. Okayama, H. Ueshima, H. Maegawa; Akabane: M. Nakamura, N. Aoki; Anzhen02: Z.S. Wu; Anzhen: C.H. Yao, Z.S. Wu; Australian Longitudinal Study of Aging: Mary Luszcz; Australian National Heart Foundation: T.A. Welborn; Beijing Aging: Z. Tang; Beijing Steelworkers: L.S. Liu, J.X. Xie; Blood Donors\u2019 Health: R. Norton, S. Ameratunga, S. MacMahon, G. Whitlock; Busselton: M.W. Knuiman; Canberra-Queanbeyan: H. Christensen; Capital Iron and Steel Company: X.G. Wu; CISCH: J. Zhou, X.H. Yu; Civil Service Workers: A. Tamakoshi; CVDFACTS: W.H. Pan; East Beijing: Z.L. Wu, L.Q. Chen, G.L. Shan; Electricity Generating Authority of Thailand: P. Sritara; Fangshan: D.F. Gu, X.F. Duan; Fletcher Challenge: S. MacMahon, R. Norton, G. Whitlock, R. Jackson; Guangzhou: Y.H. Li; Guangzhou Occupational: T.H. Lam, C.Q. Jiang; Hisayama: Y. Kiyohara, H. Arima, M. Iida; Hong Kong: J. Woo, S.C. Ho; Huashan: Z. Hong, M.S. Huang, B. Zhou; Kinmen: J.L. Fuh; Konan: H. Ueshima, Y. Kita, S.R. Choudhury; KMIC: I. Suh, S.H. Jee, I.S. Kim; Melbourne: G.G. Giles; Miyama: T. Hashimoto, K. Sakata; Newcastle: A. Dobson; Ohasama: Y. Imai, T. Ohkubo, A. Hozawa; Perth: the late K. Jamrozik, M. Hobbs, R. Broadhurst; Saitama: K. Nakachi; Seven Cities: X.H. Fang, S.C. Li, Q.D. Yang; Shanghai Factory Workers: Z.M. Chen; Shibata: H. Tanaka; Shigaraki Town: Y. Kita, A. Nozaki, H. Ueshima; Shirakawa: H. Horibe, Y. Matsutani, M. Kagaya; Singapore Heart: K. Hughes, J. Lee; Singapore NHS92: D. Heng, S.K. Chew; Six Cohorts: B.F. Zhou, H.Y. Zhang; Tanno/Soubetsu: K. Shimamoto, S. Saitoh; Tianjin: Z.Z. Li, H.Y. Zhang; Western Australia AAA Screenees: P. Norman, the late K. Jamrozik; Xi\u2019an: Y. He, T.H. Lam; Yunnan: S.X. Yao.The authors declare that they have no competing interests.; FB analyzed the data; JW, GG, THL, TO, SHJ, XF acquired the data and provided critical revision of the manuscript; KZ, SK provided critical revision of the manuscript and MW oversaw the statistical analysis and provided critical revision of the manuscript. All authors read and approved the final manuscript.RH conceived the manuscript, interpreted the data and wrote the manuscriptThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/61/prepubWebFigure 2. Hazard ratios for fatal heart failure associated with cigarette smoking (ever versus never) adjusted for age, systolic blood pressure, body mass index and stratified by sex and study in the Asia Pacific Cohort Studies Collaboration. Conventions as in WebFigure 1.WebFigure 3. Hazard ratios for fatal heart failure associated with diabetes (yes versus no) adjusted for age, systolic blood pressure, body mass index, cigarette smoking, regression dilution bias and stratified by sex and study in the Asia Pacific Cohort Studies Collaboration. Conventions as in WebFigure 1.WebFigure 4. Hazard ratios for fatal heart failure associated with 1 mmol/L increment in total cholesterol (multiply by 38.7 to obtain mg/dL) adjusted for age, systolic blood pressure, body mass index, cigarette smoking, regression dilution bias and stratified by sex and study in the Asia Pacific Cohort Studies Collaboration. Conventions as in WebFigure 1.WebTable 1. Associations between risk factors and mortality from heart failure in those with and without a history of cardiovascular disease at study baseline. Hazard ratios for fatal heart failure associated with a 10 mmHg increment in systolic blood pressure, adjusted for age, smoking, body mass index, diabetes, and regression dilution bias and stratified by sex and study in the Asia Pacific Cohort Studies Collaboration, both by subgroup and overall. Bars show 95% confidence intervals. The vertical dimension of the diamond indicates the overall estimate and the horizontal dimension indicates the 95% confidence interval. Click here for file"} +{"text": "De novo point mutations in patients diagnosed with ataxic cerebral palsy. Brain 2015; 138: 1817\u201332; 10.1093/brain/awv117.Ricardo Parolin Schnekenberg, Emma M. Perkins, Jack W. Miller, Wayne I. L. Davies, Maria Cristina D\u2019Adamo, Mauro Pessia, Katherine A. Fawcett, David Sims, Elodie Gillard, Karl Hudspith, Paul Skehel, Jonathan Williams, Mary O\u2019Regan, Sandeep Jayawant, Rosalind Jefferson, Sarah Hughes, Andrea Lustenberger, Jiannis Ragoussis, Mandy Jackson, Stephen J. Tucker, Andrea H. N\u00e9meth. The authors apologize for an incorrect Funding statement, which should read as follows:This work was supported by CNPq , Brazil, to R.P.S.; by the Wellcome Trust (093077) to M.J. and E.P., part of an Australian Research Council (ARC) grants awarded to W.I.L.D. ; grants awarded by Telethon Italy, MIUR-PRIN, Ministry of Health to M.P.; K.F. and D.S. are funded by the Medical Research Council (UK) Computational Genomics Analysis and Training programme (G1000902). Wellcome Trust Grant 075491/Z/04 to J.R.; grants from the Wellcome Trust to S.J.T. (WT084655MA); and awards to A.H.N. from Ataxia UK, Action Medical Research, The Henry Smith Charity, the Oxford Partnership Comprehensive Biomedical Research Centre funded by the Department of Health National Institute of Health Research (NIHR) Biomedical Research Centre Programme and the Thames Valley Dementias and Neurodegenerative Diseases Research Network (DeNDRoN), UK."} +{"text": "H. pylori infection and possible correlation with clinicopathological parameters.To determine the risk factors associated with in situ hybridization.Gastroduodenal biopsies were examined by rapid urease test and Gram staining. Cag A cytotoxin was detected by H. pylori acquisition reported as following: Males have 1.38 fold, rural residents have 0.63 fold, Nonsmokers have 0.39 fold, mild smokers have 18 fold, and moderate smokers have 1.4 fold while heavy smokers have 1 fold. A person who\u2019s in contact with animals has 1.52 fold risks. Illiterates and patients with primary education have 5.36 & 3 fold risk respectively. Patients under proton pump inhibitor (PPI) therapy have 1.02 fold. Patients under NSAID therapy have 3.48 fold while nonalcoholic Patients have 0.75 fold. Patients using tap water have 0.45 fold risk. H. pylori infection positively correlated with age, weight loss, and heartburn. H. pylori inversely correlated with endoscopic diagnosis, Cag A positivity, and education level. Cag A positivity correlated with animal contact and NSAID usage.Risk of H. pylori infection. Weight loss and heartburn cardinal signs for H. pylori infection. Endoscopic diagnosis and clinicopathological parameters not strictly associated with Cag A positivity.Several life style factors, education, animal contact, using of PPI, and NSAIDs increase the risk of Helicobacter pylori infection is conventional chronic bacterial infection around the world . The patH. pylori . O. OH. pyldication . No corrine with . Currental study . In Iranal study . No corrh others and in cH. pylori infection , and Cag A positive H. pylori . This comes in line with . Si. SiH. pyth other . No corrH. pylori infections without correlation between H. pylori infection and anatomical location of lesions whether in antrum, body and antrum or multiple sites , which comes in line with [H. pylori associated pathology and infection with Cag A positive H. pylori which comes in contrary with others found significant correlation between CagA and gastric and duodenal ulcers [H. pylori which comes in contrary with [H. Pylori, mucosal pathology, anatomical location in gut, and the infection with H. pylori can be estimated via clinical features of infected mucosal lining [H. pylori Infections . A correlation was reported between endoscopic diagnosis and infection with Cag A positive H. pylori which comes in line with [In current study, significant difference between groups in ine with . No corrl ulcers . No corrary with , found sl lining . Inverseine with , 47.H. pylori infection. Weight loss and heartburn considered as a cardinal signs for H. pylori infection. Endoscopic diagnosis and clinicopa-thological parameters not strictly associated with CagA positivity.In conclusion, several life style factors, education, animal contact, using of PPI, and NSAIDs increase the risk of"} +{"text": "Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations. \u2022We integrate heterogeneous molecular data of 11,289 tumors and 1,001 cell lines\u2022We measure the response of 1,001 cancer cell lines to 265 anti-cancer drugs\u2022We uncover numerous oncogenic aberrations that sensitize to an anti-cancer drug\u2022Our study forms a resource to identify therapeutic options for cancer sub-populations A look at the pharmacogenomic landscape of 1,001 human cancer cell lines points to new treatment applications for hundreds of known anti-cancer drugs. Cancers arise because of the acquisition of somatic alterations in their genomes that alter the function of key cancer genes . A numbeClinical trials are complex and expensive, and pre-clinical data that helps stratify patients can dramatically increase the likelihood of success during clinical development . Thus, pHere, we analyzed somatic mutations, copy number alterations, and hypermethylation across a total of 11,289 tumor samples from 29 tumor types to define a clinically relevant catalog of recurrent mutated cancer genes, focal amplifications/deletions,\u00a0and methylated gene promoters A\u2013S1D. ThWe built a comprehensive map of the oncogenic alterations in human tumors using data from TCGA, ICGC, and other studies C. The maThe WES dataset consisted of somatic variant calls from 48 studies of matched tumor-normal samples, comprising 6,815 samples and spanning 28 cancer types A\u2013S1D. CGEGFR, ERBB2, MET, and MYC) and homozygous deletions were captured, with 320 RACSs (38%) containing at least one known putative cancer driver gene, in addition to 531 RACSs (62%) without known driver genes. A smaller pan-cancer set (due to overlap in RACSs across cancer types) was constructed by pooling these results, comprising 425 RACSs (117 amplified and 308 deleted) D\u2013S2F.iCpGs were identified using DNA methylation array data for 6,166 tumor samples spanning 21 cancer types D. We defIn total, our multidimensional analysis of >11,000 patient tumor samples identified 1,699 cancer-specific CFEs, which were further merged into 1,273 unique pan-cancer CFEs A.http://cancer.sanger.ac.uk/cell_lines) , copy number (n\u00a0= 996), gene expression (n\u00a0=\u00a0968), and DNA methylation (n\u00a0= 957) (l_lines) B and whil_lines) A and S1El_lines) C.Of the 1,273 pan-cancer CFEs identified in patient tumors, 1,063 (84%) occurred in at least one cell line, and 1,002 (79%) occurred in at least three A. This cThe correlation between the frequency of CFEs in cell lines and patient tumors was high for the majority of the cancer types and for all three classes of CFEs . Using aR\u00a0= 0.75 across all 13 pathways) A.A previous hierarchical classification of \u223c3,000 tumors identified two major subclasses: M and C class . We expaTaken together, these results show that a sufficiently large panel of cell lines is able to capture individual clinically relevant genomic alterations, in addition to pathway alterations and global signatures of driver events.50 (drug concentration that reduces viability by 50%) or AUC (area under the dose-response curve) values values A and S4B50 values with a median Pearson correlation (R)\u00a0= 0.65 and consistent classification of cell lines as sensitive or resistant to a compound (Screened compounds included cytotoxics (n\u00a0= 19) and targeted agents (n\u00a0= 242) selected against 20 key pathways and cellular processes in cancer biology F. These e\u00a0= \u221226) . Clustere\u00a0= \u221226) .50 values. We carried out a pan-cancer, as well as a cancer-specific, analysis .We used three distinct analytical frameworks to define the contribution of CFEs to the prediction of drug sensitivity E. ANOVA BCR-ABL, EWSR1-FLI1, and EWSR1-X). Overall, for the 265 compounds, we identified 688 statistically significant interactions between unique CFE-drug pairs , with few overlapping interactions C. The efOverall, 233 of 674 (34%) CFEs were significantly associated with the response to at least one compound, and more RACSs (62%) were associated with response than were CGs (38%). The importance of these two classes of CFEs varied by cancer type and was related to their prevalence C and S4G10 p value 3.68 vs. 4.56).We identified significant associations for the majority of compounds . When compounds were classified by their nominal target into 20 specific biological processes F, CFEs bWe performed ANOVA on randomly downsampled subsets of cell lines and evaluated our ability to retain the set of statistically significant associations. The number of associations exponentially decreased as the number of cell lines was reduced, with a loss of \u223c80% of pan-cancer associations when using 500 cell lines . This hiBRAF, ERBB2, EGFR, and the BCR-ABL fusion gene and sensitivity to clinically approved drugs in defined tumor types, as well as associations between KRAS, PDGFR, PIK3CA, PTEN, CDKN2A, NRAS, TP53, and FLT3 with drugs that target their respective protein products or pathways (EGFR mutation in lung adenocarcinoma (LUAD) and resistance to EGFR-targeted therapies (Gefitinib and Afatinib) D, as welnhibitor C and drugs targeting those CFEs I. For ex\u22123, FDR\u00a0< 25%, and \u0394 > 1, for both the cell line populations included in the test) , Sorafenib , Sunitinib , and XL-184 ; PTEN mutations associate with sensitivity to an AKT inhibitor in COAD/READ . The chemotherapeutic Mitomycin C is widely used to treat BLCA, and here, we detect, in the BLCA specific analysis, a sensitizing interaction with mutations in TP53 that are highly prevalent in this cancer type. In LUSC cells, loss-of-function mutations in the DNA methyltransferase MLL2 are associated with sensitivity to the clinical anti-androgen Bicalutamide ; the BCL-2 inhibitor, ABT-263, shows activity in COAD/READ cells that harbor focal amplifications of MET or FOXA1/CRNKL1 , events found in almost 60% of colorectal tumors; and truncating mutations in the co-repressor of BCL6, BCOR, statistically interact with sensitivity to a PKC beta inhibitor in STAD C. For ex in STAD D, and deInterestingly, 24 of the 262 associations are driven by RACSs that do not contain known cancer genes C and S2D50 values for a drug, for example, \u201cif RAS or RAF mutated, then sensitive to MEK inhibition\u201d . Across the cancer-specific datasets, on average, 24% of the drugs were explained by the inferred logic models (In the pan-cancer dataset we found that for 69% (182 of 265) of the drugs, the ICc models A. We terc models B. Althouc models B. This ic models C.We observed that CGs had the largest role in explaining drug response, followed by RACSs and the pathway activities derived from gene expression . The smaKRAS or BRAF improved the precision and recall compared to single predictor models to explain cell line sensitivity to a number of MEK and RAF inhibitors of cell lines sensitive to the ERRB2/EGFR inhibitor Afatinib, whereas considering only the EGFR amplified cell lines accounts for only 32% (7 out of 22) of the sensitive cell lines (FAT1/IRF2 locus and are TP53 mutant show increased sensitivity to the ERRB2/EGFR inhibitor Lapatinib. This is achieved at higher precision (57% instead of 45% for the single predictor model), but at a lower recall (80% instead of 100%) F. Collec50 values from the GDSC and CCLE studies and AUC values from the CTRP study .We sought to validate our pharmacogenomic models using independent drug sensitivity datasets from the Cancer Cell Line Encyclopedia (CCLE) and the \u22129; CCLE: p\u00a0= 0.01; We performed ANOVA on the overlapping set of cell lines/compounds. We validated 53% (19 of 36 on CTRP) and 86% (6 of 7 on CCLE) of the testable sensitivity associations identified in the GDSC, and 21% (6 of 29 on CTRP) and 0% (0\u00a0of 7 on CCLE) of testable resistance associations . As inp50 values (R) of observed versus predicted IC50 values. For each of the 265 compounds, we built pan-cancer and cancer-specific models (for 18\u00a0cancer types) and considered a model with a corresponding Here, we refer to EN models using IC0 values A, but ve0 values A. We assedictive .In a pan-cancer analysis, the most predictive data type was gene expression, closely followed by the tissue of origin of the cell lines A. By comNext, we compared the most predictive data types in pan-cancer versus cancer-specific analyses B and 6C.In a cancer-specific analysis, the majority of lead models are based solely on genomics features D and 6E.http://www.cancerrxgene.org). To the best of our knowledge, this is the largest and most extensively characterized panel of cancer cell lines and should enable a broad range of studies linking genotypes with cellular phenotypes.Cancer cell lines are important tools for drug development. Here, we have extended previous efforts with the systematic expansion of the pharmacological, genomic, transcriptomic, and epigenetic characterization of 1,001 human cancer cell lines. These datasets can be investigated through the COSMIC and Genomics of Drug Sensitivity in Cancer Web portal are represented by a single cell line or not at all, and coverage by cancer type is variable. As we enter an era of precision cancer medicine, where many drugs are active in small molecularly defined subgroups of patients , the scPharmacogenomic screens in cancer cell lines are an unbiased discovery approach for putative markers of drug sensitivity. We identified a wealth of molecular markers of drug sensitivity, including completely novel associations not easily explained with our current knowledge. With appropriate validation and follow-up studies, these putative biomarkers may aid patient stratification and help to explain the heterogeneity of clinical responses.BRAF mutant melanoma patients treated with BRAF inhibitors show heterogeneity of response that may be explained by the presence of additional molecular alterations A. Overal tumors) . This suUsing machine learning, we determined that within each specific cancer type, genomic features generated the most predictive models, with the addition of methylation data further improving our models. While informative in the pan-cancer setting, baseline gene expression data was less informative in the more clinically relevant tissue-specific setting. Prioritizing the design of diagnostics that deliver driver mutations, copy number alterations, and DNA methylation profiles might be the most cost effective means in the short-term to stratify patients for cancer treatment.The clinical development of molecularly targeted cancer therapies remains a formidable challenge. Our current analysis is restricted by the availability of patient genomic datasets, the cell lines and compounds screened, and methodological and biological variables, as well as the inherent limitation associated with the use of in\u00a0vitro cancer cell lines. Nonetheless, our results represent a comprehensive attempt to describe the landscape of clinically relevant pharmacogenomics interactions in cellular models of cancer, complementing previous efforts . The datGenomic data for a panel of 1,025 genetically unique human cell lines were assembled from the COSMIC database. 1,001 cell lines were included in this study E. Varianhttps://zenodo.org/record/16732#.VbeVY2RViko).Variant data from sequencing of 6,815 tumor normal sample pairs derived from 48 different sequencing studies were compiled . To\u00a0aid For primary tumors, raw data for 6,035 methylation samples, covering 18 tumor types, were downloaded from the TCGA data portal. For the cell lines, data were generated in-house as described in the The selection of cancer-driver genes (together with the variant recurrence filter) of the recurrently copy-number-altered chromosomal regions and the\u00a0informative CpG islands is detailed in the Cell line pellets collected during exponential growth in RPMI or DMEM/F12 were lysed with TRIzol (Life Technologies) and stored at \u221270\u00b0C. Following chloroform extraction, total RNA was isolated using the RNeasy Mini Kit (QIAGEN). DNase digestion was followed by the RNAClean Kit (Agencourt Bioscience). RNA integrity was confirmed on a Bioanalyzer 2100 (Agilent Technologies) prior to labeling using 3\u2032 IVT Express (Affymetrix). Microarray analysis was performed as described in the All analyses evaluating the extent to which cell lines resemble primary tumors are detailed in the 50),and area under the curve [AUC]) through a multilevel mixed model and detailed in the the For each drug an ANOVA model was fitted to correlate drug response with the status of Cancer Functional Events (CFEs), as described in Conceptualization, F.I., T.A.K., D.J.V., G.R.B., M.P.M., M.Sc., L.F.A.W., J.S.-R., U.M., and M.J.G.; Methodology, F.I., T.A.K., D.J.V., G.R.B., M.P.M., M.Sc., S.B., U.M., and M.J.G.; Software, F.I., T.A.K., D.J.V., M.P.M., M.Sc., T.C., H.L., and E.v.D.; Validation, F.I., T.A.K., D.J.V., M.P.M., N.A., S.B., H.L., P.G., and M.J.G.; Formal Analysis, F.I., T.A.K., D.J.V., M.P.M., and M.Sc.; Investigation, G.R.B., S.B., P.G., T.M., and L.R.; Resources, D.J.V., G.R.B., M.Sc., E.G., S.B., H.L., P.G., E.v.D., H.C., H.d.S., H.H., T.M., S.M., L.R., X.D., R.K.E., Q.L., X.M., J.W., T.Z., N.S.G., S.S., D.T., N.L.-B., P.R.-M., M.E., D.A.H., C.H.B., U.M., and M.J.G.; Data Curation, F.I., D.J.V., G.R.B., M.Sc., E.G., H.L., P.G., H.C., H.d.S., H.H., S.M., S.S., M.So., D.T., N.L.B., P.R.-M., L.F.A.W., J.S.-R., U.M., and M.J.G.; Writing \u2013 Original Draft, F.I., T.A.K., D.J.V., G.R.B., M.P.M., U.M., and M.J.G.; Writing \u2013 Review & Editing, F.I., T.A.K., D.J.V., G.R.B., M.P.M., M.Sc., N.A., L.F.A.W., J.S.-R., U.M., and M.J.G.; Visualization, F.I., T.A.K., M.P.M., M.Sc., and E.G.; Supervision, D.A.H., M.R.S., C.H.B., L.F.A.W., J.S.-R., U.M., and M.J.G.; Project Administration, F.I., U.M., and M.J.G.; Funding Acquisition, D.A.H., C.H.B., M.R.S., L.F.A.W., J.S.-R., U.M., and M.J.G."} +{"text": "Scientific Reports5: Article number: 1287910.1038/srep12879; published online: 08142015; updated: 09212015The Competing financial interests statement in this Article should read:\u201cThe University of Bergen has pending patent applications on the screening technology. Family members of the European patent, Application No. 13194536.2 \u2013 1408 are pending. The six authors T.K., H.-H.G., E.H., D.M.F., A.B. and I.R.M. are named as inventors in these applications\u201d."} +{"text": "The citation of:J. Vis. 14, 1\u201315. doi: 10.1167/14.12.10Weech, S., McAdam, M., and Troje, N. F. (2014). What causes the facing-the-viewer bias in biological motion? should be corrected as:J. Vis. 14, 1\u201315. doi: 10.1167/14.12.10Weech, S., McAdam, M., Kenny, S., and Troje, N. F. (2014). What causes the facing-the-viewer bias in biological motion? The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "While not members of the Board of Editors, Invited Editors serve an important role in the review process. Invited Editors are experts in their fields of research who add an additional level of quality to the review process. An Editor may assign a paper to an Invited Editor when he/she would like to have an additional expert opinion of the reviews or when the subject area falls outside the Editor\u2019s primary area of expertise.On behalf of the Editors of The time and effort expended by the following experts in handling articles have been essential to ensuring the high quality of our publications, and their help is greatly appreciated.Eric AlmJ. Andrew AlspaughLisa Alvarez-CohenRama Rao AmaraDavid AndesGustavo ArrizabalagaJimmy D. BallardJames BannJoseph T. BarbieriDennis A. BazylinskiThomas BernhardtMelanie BlokeschElhanan BorensteinJon P. BoyleRoland BroschHarlan D. CaldwellAndrew CamilliEmmanuelle CharpentierCarton W. ChenJose C. ClementeFevzi DaldalFrank van de VeerdonkWillem M. de VosThomas DickDirk P. DittmerTamara L. DoeringPaul DunmanGary M. DunnyRoselyn J. EisenbergSean ElliottFrancis EnnisJose A. EsteEdward J. FeilReinhard FischerVance G. FowlerDara W. FrankJames A. FraserPhilippe GerardGustavo H. GoldmanAndrew GoodmanHeidi Goodrich-BlairBill HanageSimon R. HarrisAnton HartmannXiaosong HeDavid R. HendrixsonJoseph M. HyserIvan JunierSheryl JusticeJoerg KaemperFatah KashanchiDaniel B. KearnsDamian J. KrysanMichael T. LaubWayne LencerBruce R. LevinPetra Anne LevinSusan LiebmanXiaorong LinPeter N. LipkeVictor de LorenzoStephen LoryAna MaldonadoAnthony W. MaressoAnthony T. MaurelliHoura MerrikhSamuel I. MillerCesare MontecuccoDonald A. MorrisonSamuel M. MoskowitzTarek MsadekMihai G. NeteaMark NitzGeorge O'TooleR. Thane PapkeEleftherios T. PapoutsakisJohn S. ParkerMatthew R. ParsekVicente PlanellesLaurent PoirelMaria I. PozoRajendra PrasadVenigalla RaoDavid A. RaskoFederico ReyEleanor M. RileyJason W. RoschErica Ollmann SaphireThomas Mitchell SchmidtThamarai SchneidersJulia A. SegreAngela SessitschAnita SilEric P. SkaarDavid SkurnikThomas E. SmithgallAlfred Michael SpormannChristina L. StallingsBoris StriepenCurtis SuttleJohn M. TaylorTeresa ThielJustin Adam ThorntonJan TommassenBruce E. TorbettVictor J. TorresMark TravassosAna TravenElaine I. TuomanenGilles P. van WezelFabrice VavreAlan W. WalkerGary P. WangDavid WangRoy D. WelchMarvin WhiteleyKelly WrightonOtto O. Yang"} +{"text": "Scientific Reports6: Article number: 2288110.1038/srep22881; published online: 03112016; updated: 04222016The original version of this Article contained an error in the title of the paper, where the word \u201cOccurring\u201d was incorrectly given as \u201cOccuring\u201d.In addition, the Acknowledgements section was incomplete.\u201cWe are grateful to J. Britton-Davidian, T. J. Robinson, and J. Watson for their contributions in collecting the founder animals, J. Perez and M. Perriat-Sanguinet for their help in maintaining the breeding colony, P.-A. Crochet for advice on statistical analyses and C.M.-S. Dufour and Y. Latour for helpful discussions. This is a publication ISEM no. 2016-45.\u201dnow reads:\u201cWe are grateful to J. Britton-Davidian, T. J. Robinson, and J. Watson for their contributions in collecting the founder animals, J. Perez and M. Perriat-Sanguinet for their help in maintaining the breeding colony, P.-A. Crochet for advice on statistical analyses and C.M.-S. Dufour and Y. Latour for helpful discussions. This work was supported by the French National Research Agency , and the Del Duca Foundation . This is a publication ISEM no. 2016-45.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "We wish to make the following correction to the published paper . In the 1 Department of Epidemiology and Biostatistics, Jilin University School of Public Health, Changchun 130021, China; beyond.hehe@163.com (Z.L.); yaoyan@jlu.edu.cn (Yan.Y.); hanwq1987@foxmail.com (W.H.); yuyaqin5540@163.com (Yaq.Y.); ywliu@jlu.edu.cn (Y.L.); taoyuchun@163.com (Y.T.); koucg@jlu.edu.cn (C.K.); jianglingling.2008@163.com (L.J.); Yinyt13@mails.jlu.edu.cn (Yut.Y.)2 Department of Food and Nutrition, Jilin University School of Public Health, Changchun 130021, China; qingbao7@126.com3 Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA; huiping.zhang@yale.edu* Correspondence: li_bo@jlu.edu.cn; Tel./Fax: +86-431-8561-9451We apologize to the authors of the article and readers of the journal for any inconvenience."} +{"text": "The age-adjusted cancer death rates increased significantly from 1970 to 1990 in each census region in the United States. The rate increased an average of 0.16% per year in the Northeast, 0.38% in the Midwest, 0.71% in the South, and 0.27% in the West. Since 1990, the rates have decreased at an ever faster rate, down on average by 1.41% in the Northeast, 1.02% in the Midwest, 1.15% in the South, and 1.30% in the West each year. At the beginning of the period, rates were highest in the Northeast, but since the late 1990s, rates in the South and Midwest have been higher. Throughout the period, the rates were lowest in the West census region.Source: National Vital Statistics System. Mortality public use data files, 1970\u20132013. Available at http://www.cdc.gov/nchs/data_access/vitalstatsonline.htm.Reported by: Jiaquan Xu, MD, jax4@cdc.gov, 301-458-4086."} +{"text": "This new calibration atlas is based on frequency rather than wavelength calibration techniques for absolute references. Since a limited number of absolute frequency measurements is possible, additional data from alternate methodology are used for difference frequency measurements within each band investigated by the frequency measurements techniques. Data from these complementary techniques include the best Fourier transform measurements available. Included in the text relating to the atlas are a description of the heterodyne frequency measurement techniques and details of the analysis, including the Hamiltonians and least-squares-fitting and calculation. Also included are other relevant considerations such as intensities and lincshape parameters. A 390-entry bibliography which contains all data sources used and a subsequent section on errors conclude the text portion.\u22121. Some gaps in the coverage afforded by OCS and N2O are partially covered by NO, CO, and CS2. An additional region from 4000 to 4400 cm\u22121 is also included.The primary calibration molecules are the linear triatomics, carbonyl sulfide and nitrous oxide, which cover portions of the infrared spectrum ranging from 488 to 3120 cm#39, Wavelength Calibration Tables.The tabular portion of the atlas is too lengthy to include in an archival journal. Furthermore, different users have different requirements for such an atlas. In an effort to satisfy most users, we have made two different options available. The first is NIST Special Publication 821, which has a spectral map/facing table format. The spectral maps (as well as the facing tables) are calculated from molecular constants derived for the work. A complete list of all of the molecular transitions that went into making the maps is too long (perhaps by a factor of 4 or 5) to include in the facing tables. The second option for those not interested in maps is the complete list (tables-only) which is available in computerized format as NIST Standard Reference Database The primary purpose of this work is to provide an atlas of molecular spectra and associated tables of wavenumbers to be used for the calibration of infrared spectrometers. A secondary purpose is to furnish a detailed description of the infrared heterodyne frequency measurement techniques developed for this work. Additionally, we provide a bibliography of all the measurements used in producing these tables, as well as to provide a description of how those measurements were combined to calculate energy levels, transitions, and uncertainties. We also provide useful related information such as line intensities, pressure broadening coefficients, and estimates of pressure shifts of spectral lines. This book does not include an exhaustive list of all the weaker transition frequencies currently available, especially for the less abundant molecular species. Such a list, containing over 10 000 transitions for OCS, is available, however, in computerized format as NIST Standard Reference Database 39. To put this work in proper perspective, some background, philosophy, and the status of existing atlases are discussed in the following sections.\u22121) instruments. Other compilations [1.4\u20131.7] and other sections of the IUPAC compilations were devoted to data intended for the calibration of high resolution instruments (resolution better than 0.5 cm\u22121). This book falls into the latter category. Of the earlier compilations, only the work of Guelachvili and Rao [1.7] provides calibration data that are consistently more accurate than \u00b10.01 cm\u22121.Over the last 35 years could use even more accurate calibration data.A number of commercially available infrared spectrometers are capable of recording spectra with a resolution of 0.06 cm\u22121, while for a Fourier transform spectrometer (FTS) a high resolution scan may cover hundreds of wavenumbers. This means that for many purposes calibration standards should be no more than 100 cm\u22121 apart, while for other purposes standards no more than 0.5 cm\u22121 apart are required throughout the infrared region of interest. Our work here presents a compromise between these two requirements.Most high resolution spectrometers are not capable of broad frequency scans. For the most accurate measurements the calibration should be applied to each spectral scan. This requires that at least one and preferably several calibration points be available within the scanning range of the spectrometer. For tunable diode laser spectrometers, a single scan may cover only 0.5 cmIn our opinion, all previous compilations of infrared wavenumber standards have suffered from the lack of a consistent effort to draw together a number of experimental measurements to arrive at a well determined set of molecular energy levels which could be used to determine frequency (or wavenumber) standards for a number of bands throughout the infrared spectral region. The present compilation provides a model for producing such frequency or wavenumber calibration data.It is appropriate at this point to define some of the terminology used in this book clarifying an important distinction: in some places emphasis is placed on the difference between frequency measurements and wavelength measurements. All measurements that can be reduced to counting frequencies or frequency differences are frequency measurements, while all measurements that are really comparisons of wavelengths (or wavenumbers), including counting fringes, are wavelength measurements. Fourier transform measurements, for instance are truly wavelength measurements even though counting may be involved.7. One of the most insidious problems with wavelength measurements is the risk (or ease) of incurring systematic errors and the virtual impossibility of detecting them.Most measurements of infrared absorption spectra are made using grating or Fourier transform spectrometers. These measurements are truly wavelength measurements. They rely for calibration on measuring the difference in wavelength of some calibration feature and the feature of the spectrum to be determined. For FTS instruments, the position of the moveable mirror must be determined, while for grating instruments one is essentially calibrating the grating angle and the spacing of the grooves of the grating. Very often these instruments use more than one beam and compare the wavelength of a calibration beam with the beam carrying the spectra of interest. With FTS instruments a helium-neon laser beam is often used to monitor the mirror position. In other cases a single beam is used, but one cannot be certain that the beam properties are independent of wavelength. With all wavelength measuring instruments, it is extremely important that the calibration light beam follow precisely the same path through the spectrometer as the beam of light being measured. Problems of wavelength-dependent diffraction effects become very important for measurements intended to approach or exceed one part in 10The great advantage of frequency measurements is that they simply depend on frequency counting techniques. Over the years considerable attention has been given to electronic techniques of frequency counting, and simple, accurate, well calibrated devices are readily available. The accuracy of frequency techniques does not depend on whether or not the beams are perfectly collinear or have parallel wavefronts. If a countable signal is obtained, it will be correct. The frequency of light does not depend on the medium, nor does it depend on the angle from which it is viewed.2O were chosen because they are stable, safe to handle, easily obtainable, and well documented in terms of good measurements reported in existing literature. Furthermore, they are particularly amenable to the accurate calculation of energy levels from a relatively simple Hamiltonian.Over the past decade we have striven to provide infrared heterodyne frequency measurements on the transitions and energy levels of several simple molecules, which are good candidates for frequency calibration standards. OCS, CO, and NFor these molecules a least-squares fit of many transitions (over 3000 OCS lines for example) has permitted the determination of all of the lower energy separations, using frequency differences referred to the primary cesium frequency standard. Due to statistical improvements from a large data base, transition frequencies between these energy levels can be calculated with greater accuracy than any single measurement with its attendant random errors.frequency measurements because they are less susceptible to unknown systematic errors than are wavelength measurements. Particular importance was attached to estimating the uncertainties in the transition wavenumbers; see the discussion in the chapter on errors (Sec. 4).Although we have had to use some FTS (wavelength) measurements to help define certain higher order rotational constants, for the most part the energy levels were determined from As with any good calibration standard, a number of different measurements were used in determining the energy levels and transition frequencies. However, only a few laboratories have used frequency measurement techniques in the infrared region and very few of the more accurate sub-Doppler frequency measurements have been made, so it is somewhat premature to claim the level of accuracy that we desire for infrared standards. Nevertheless we are encouraged by the convergence of different FTS measurements on the same values for the band centers as frequency measurements. Our publication of this atlas at this time is dictated by the need to provide good calibration data now, rather than await the arrival of a perfect atlas.2O gases is insufficient to provide calibration data everywhere within the infrared, so we have had to provide heterodyne measurements on other molecular species, such as CS2 and NO in order to fill some of the gaps. The user will still note that many gaps remain in the coverage of these tables. To some extent these gaps may be filled by using the data provided by the compilation of Guelachvili and Rao [1.7]. We also expect that future measurements will provide calibration data where none are currently available.Of course the combination of OCS, CO, and N\u22121) even though the values were primarily determined from frequency measurements. The conversion from frequency units to wavenumber units was made by using the defined value of the velocity of light, c = 299 792 458 m/s. Since the tables are given in wavenumbers, we often use the terms wavenumber and frequency interchangeably in the text, but the term wavelength is reserved for quantities determined by wavelength measurements and must not be confused with frequency measurements.Since most workers are more comfortable with calibration data given in wavenumber units, the tables in this book are given in wavenumbers .[1.1] A. R. Downie, M. C. Magoon, T. Purcell, and B. Crawford, Jr., The calibration of infrared prism spectrometers, J. Opt. Soc. Am. [1.2] Tables of Wavenumbers for the Calibration of Infrared Spectrometers, prepared by the Commission on Molecular Structure and Spectroscopy of IUPAC, Butterworths, Washington (1961).[1.3] A. R. H Cole, Tables of Wavenumbers for the Calibration of Infrared Spectrometers, 2nd edition, prepared by the Commission on Molecular Structure and Spectroscopy of IUPAC, Pergamon Press, New York (1977).64A, 29\u201348 (1960).[1.4] E. K. Plyler, A. Danti, L. R. Blaine, and E. D. Tidwell, Vibration-rotation structure in absorption bands for the calibration of spectrometers from 2 to 16 microns, J. Res. Natl. Bur. Stand. (U.S.) 67A, 351\u2013358 (1963).[1.5] K. Narahari Rao, R. V. deVore, and Earle K. Plyler, Wavelength Calculations in the Far infrared (30 to 1000 microns), J. Res. Natl. Bur. Stand. (U.S.) [1.6] K. Narahari Rao, C. J. Humphreys, and D. H. Rank, Wavelength Standards in the Infrared, Academic Press, New York (1966).[1.7] G. Guelachvili, and K. Narahari Rao, Handbook of Infrared Standards, Academic Press, Inc., San Diego (1986).2O laser transition frequencies made at the National Research Council of Canada [5.183] were also used here. This chapter describes the techniques that have been used in the NIST Boulder frequency measurements in order to familiarize the reader with the techniques that have evolved. We hope that such familiarity will give greater confidence in the accuracy of the results.At the present time the only frequency measurements that have been made on infrared absorption spectra of molecules treated in this book are those made in the NIST Boulder Laboratories [5.73],2 laser served as the local oscillator for these heterodyne measurements. For this chapter, the term local oscillator is reserved for the fixed-frequency oscillator which carries the reference frequency information (near the frequency of the molecular transition to be measured) to the mixer or heterodyne detector. For each OCS measurement, the frequency of a tunable diode laser (TDL) was locked to the peak of a selected (OCS) absorption line with an assigned uncertainty, \u03b4vlock, given by \u00b1 1/2\u0394vDopp/SNR, where \u0394vDopp is the full Doppler width at half maximum and SNR is the signal-to-noise ratio of the first derivative lock signal. The frequency of the locked TDL was compared with the frequency of the CO2 laser frequency standard by mixing the TDL and CO2 laser radiation in a fast HgCdTe detector. The resulting difference-frequency beatnote was measured with the aid of a spectrum analyzer and a marker oscillator . The frequency of the OCS transition was the sum of the CO2 laser frequency and the appropriately signed beatnote frequency.The first heterodyne frequency measurements on carbonyl sulfide (OCS) were made in the NIST Boulder Labs. A frequency-stabilized CO2 laser standard frequencies [5.94]. In a third type of measurement, a tunable color center laser (CCL) was the local oscillator. In this case, the CCL (which was locked to the transition of interest) was heterodyned directly with a frequency synthesized from CO2 laser standards [5.304]. All three techniques are discussed in detail later in this chapter.Similar sets of measurements have also been made in which the TDL was heterodyned against a CO laser local oscillator (or transfer oscillator). In these cases the frequency of the CO laser was simultaneously measured relative to a frequency synthesized from combinations of CO2 laser or a CO laser transition frequency. Those transitions which were blended with nearby transitions from other bands or isotopic species of the molecule of interest were deleted from this subset. An attempt was then made to select (from the candidates available at this point) and measure those transitions which permitted the best determination of the constants. As a minimal set, these included low-J transitions in both the P- and R-branches in order to determine the band center, intermediate-J transitions for determining the B -value, and high-J (60 to 100 depending on the particular band strength) transitions for the centrifugal distortion constants. If possible, additional measurements were made in order to cover the entire band with the smallest gaps possible. This served to increase the redundancy and to minimize extrapolated values in the calculated frequencies.The determination of the spectroscopic constants for a particular band of a selected molecule was based on a number of measurements such as those described above. Some preliminary considerations for selection of the particular transitions to be measured were as follows. A review of the set of transitions of a particular band of interest served as a starting point. This set was reduced immediately to those transitions whose frequencies were within 10 GHz (the approximate combined bandpass limit of the HgCdTe detector-rf-amplifier that was used) of the frequency of a CO\u22121 or so and typical TDL frequency coverage (guaranteed by the vendor) was 15 cm\u22121, although many times the coverage turned out to be larger. Within the 15 cm\u22121 region, there were usually holes in coverage and it was necessary to buy the TDLs in pairs. An additional factor which was not within the experimenter\u2019s control concerned frequency holes (regions where the beatnote was not discernible) in the bandpass of the combination of the HgCdTe detector and the rf amplifiers which follow it. These two factors were the final restrictions on the set of measurements which were used to determine the spectroscopic constants for the band.In some instances, it was not possible to realize the above goals. The region of interest often covered 100 cm2 lasers used in these measurements were constructed by the late F. R. Petersen [2.1]. These had gratings for line selection and output mirrors typically coated for 85% transmission. In order to render the output beams nearly parallel, compensated output coupling mirrors were utilized. By compensated, we mean that the anti-reflection coated surface of the mirror was formed with a smaller radius of curvature than the reflecting concave surface. Irises at both ends were available for mode discrimination and control of the power output, which was 1 to 3 W. These lasers were equipped with internal absorption cells (filled to a pressure of 5.3 Pa (40 mTorr) of carbon dioxide) to provide frequency stabilization by the Freed-Javan technique [2.2]. Although some seven isotopic combinations of CO2 have been the object of extensive frequency measurements, only three isotopes have been used for the NIST heterodyne frequency measurements. These were 12C16O2 (626), 13C16O2 (636) and 12C18O2 (828). .) In addition to the 1.25 m lasers, a 2 m laser with a similar grating and compensated output mirror was used for high-J and hot band transitions. This longer laser has been operated with the three different isotopic gases.The 1.25 m long CO2 transitions were initially related to the cesium standard in an NBS experiment published in 1973 . This was an experiment in which the frequency of the methane stabilized HeNe laser was measured. A new wavelength measurement of the same methane transition was concurrently completed. The combination of these two quantities led to a new (at that time) value for the speed of light, 299 792 456.2(1.1) m/s [2.4].The frequencies of the COSince 1973 several different international laboratories have repeated this frequency measurement experiment with minor variations and confirmative measurements have led to a new value for the speed of light which is now defined to be 299 792 458 m/s [2.6]. The proposal and expected acceptance of this new definition provided impetus to extend frequency measurements to the visible portion of the spectrum. Major efforts at NIST-Boulder accomplished this objective and experiments were published in 1983 by Pollock et al. [2.7], and by Jennings et al. [2.8].\u03bcm. A best value for this transition was determined from the most accurate results of the international measurements. The P1(50) transition of a stabilized 13CO2 laser was measured relative to the stabilized HeNe laser, which was assumed to oscillate at the frequency 88 376 181.609\u00b10.009 MHz. The frequency resettability of the CO2 laser was reported to be within 5 parts in 1011, which is better than the 1 part in 1010 uncertainty in the frequency of the HeNe laser. transition to measure other CO2 transitions and to generate improved calibration tables.)13CO2 transition P1(52) was phase-locked to P1(50) by means of a stabilized 62 GHz klystron. The synthesis scheme used to arrive at the CCL frequency is indicated in \u03bcm HeNe laser frequency was locked to the frequency of the dye laser, which was in turn locked to the frequency of the o hyperfine component of the visible (576 nm) 127I2 17-1 P(62) transition. The CCL was in turn locked to the frequency of the 1.15 \u03bcm HeNe laser. Both the HeNe and the CCL served as transfer oscillators in this scheme. The comparison was made at the CCL-CO2 laser point of the chain. In a separate experiment, the HeNe laser was locked to its Lamb dip and that frequency was determined. The 13CO2 frequency listed in 2 laser to remove the dither) and is not the frequency of the center of the transition. The values for the two higher frequencies are given in To continue with the sketch, we note that a second 12C16O2 isotope are based on the most recent values (which made use of the above results) which were published in 1983 by Petersen et al. [2.9]. The stated 1 \u03c3 uncertainties for the calculated tables based on these measurements are smaller than 5 kHz for the CO2 transitions (J < 40) which were used in the infrared heterodyne measurements. Subsequent CO2 measurements relative to the values of Petersen were made by Freed and coworkers at MIT [2.10]. The uncertainties in the MIT values are also less than 5 kHz for the 13C16O2 transitions (and less than 10 kHz for the 12C18O2 transitions) used here. Note that the 1.25 m CO2 lasers used in the TDL measurements were first generation lasers and that the numbers given in The frequencies currently used for the 13CO2 hot band which extend the useful range of standard reference frequencies. These frequencies were determined from NIST measurements in which the 2 m CO2 laser and an external reference cell were used. While measurements were made on both the 636 and 626 isotopes , only the 636 frequencies were used for subsequent TDL measurements. The 2 \u03c3 uncertainties for the transitions used for OCS measurements were less than 80 kHz.Listed in 2 laser region, the CO2 frequencies given in some of our papers were rounded to the nearest 0.1 MHz. However, the full accuracy of the CO2 frequencies was retained for calculating or synthesizing the CO frequencies and the CO frequency was then rounded to the nearest 0.1 MHz.For the measurements in the CO2O measurements [5.243].The measurement procedure has evolved over the course of this work . A brief history of the TDL refrigeration evolution and the details of the apparatus and procedure currently in use will be described here. For considerations involving the TDL, refer to The first commercially available TDL spectrometers featured liquid helium Dewars as the refrigeration system. Our initial system used a 4 L helium Dewar. It was necessary to use an assortment of stainless steel shims between the Dewar\u2019s OFHC (oxygen free high conductivity) copper cold surface and the TDL in order to vary the temperature (and operating wavenumber) of the TDL. The use of liquid helium was inconvenient, changing shims was cumbersome, and the resulting temperature cycling of the TDLs was reputed to shorten their lifetime; nevertheless a narrow TDL linewidth was generally observed.As the demand for TDLs increased, vendors began experiencing difficulties in growing semiconductors that would meet the customers\u2019 specified frequency region while operating in the 4 to 10 K range. The materials problem became more tractable as the temperature constraint was removed by selling to the customers closed-cycle coolers with 10 to 70 K operating capabilities. Soon it became nearly impossible to obtain TDLs operable at helium temperatures. Most of our measurements were made using a closed-cycle cooler. This was an improvement in many areas, however in spite of an isolation scheme, some residual vibrations from the cooler\u2019s piston were transmitted to the TDL, resulting in the famous jitter linewidth which is familiar to all TDL users. The vendor has made two additional isolation improvement schemes available and while these appear worthwhile, they are still not the ultimate solution.Currently, the NIST liquid helium Dewar has been modified to accommodate a four-laser mounting platform (including the heater coils and temperature sensing diodes) from a closed-cycle cooler. While helium consumption is too high for most of the TDLs available to us, this does offer promise with the recent advent of the higher temperature MBE (molecular beam epitaxy) TDLs. A few of these are now available and operate in the temperature range accessible with liquid nitrogen (70 to 120 K if a heater is available).Both the Dewar and closed-cycle refrigerator are interchangeable in that they were compatible with the laser control module (current controller) and temperature control system. Both the control module and temperature controller have also been upgraded to reduce current noise and temperature instabilities; these upgrades have proved worthwhile. The particular type of refrigeration is not specified in f/1 lens and directed with a flat mirror and off-axis parabolic mirror into a 0.8 m Ebert-Fastie monochromator. A second off-axis parabolic mirror recollimated the TDL beam after it emerged from the monochromator. A portion of the beam was split off and passed through an absorption cell to a detector which was used initially in recording the spectra and later for the TDL locking procedure. The monochromator and a solid 3 in germanium etalon were used to help identify the particular molecular transition of interest. Once the transition had been identified, the kinematic mirror mount directing the TDL beam through the etalon was removed and the TDL beam was then focused on the HgCdTe mixer element. At this time, both the entrance and exit slits were removed from the monochromator, in order to eliminate the fringes or channel spectra which the slits may cause via feedback to the laser.After passing through the AR-coated ZnSe window of the refrigeration stage, the TDL radiation was collimated with an AR-coated 2 laser (or CO laser as described in the next section). TDL linewidths of several hundred megahertz are not uncommon at higher currents (higher gains) when viewed for integration times of several seconds. Next, the current was reduced (while increasing the temperature to maintain frequency) until an acceptable (10 to 30 MHz), or at least the narrowest attainable, linewidth was achieved for a measurement.At this point in the procedure, it was useful to measure the TDL linewidth by heterodyning its output with that from a COAssuming the best conditions, that is, a strong TDL (0.5 mW for example) with a single mode that has a flat power versus wavelength curve, a narrow TDL linewidth, and a well isolated and intense line for a locking reference, we could likely make a measurement with an uncertainty of less than 1 MHz. While these conditions sometimes prevail, more often, they do not.It is germane to discuss here the TDL locking procedure and some of the ways we have minimized errors that can creep into a measurement. After the chopper was removed from the TDL beam path, the TDL was frequency-modulated at 4.5 kHz and a first derivative scheme was used to lock the TDL frequency. In this procedure, the frequency of the radiation output of the TDL was tuned from well below the molecular transition to well above it, and the resulting derivative signal (including the baseline and the absorption line) was traced by the recorder. were all employed. Cells of absorbing gases (for isolation) were placed in the TDL beam path in a few instances although it was not possible for most spectral regions.2. The 3 dB bandwidth of this detector was 1 GHz. Power from the gas laser was focused with a 40 cm focal length lens and then reflected off the beam splitter in such manner as to make the gas laser beam collinear with the TDL beam and to make the beam waists coincide.The portion of the TDL beam passing through the first beam splitter in After initial observation of the beatnote, the amplitude was maximized by fine adjustment of the focusing lenses. It was also necessary to ascertain that the beatnote observed on the spectrum analyzer was the one of interest. This was particularly relevant when using the CO laser. On some occasions, the first beatnote observed was due to the TDL radiation mixing with that from a nearby unintended CO transition which could not be prevented from lasing along with the CO transition of interest. Mul timode TDLs are also the source of extraneous beatnotes.Once we determined that the observed beatnote was the one of interest, the TDL frequency was scanned by changing the current and the beatnote was followed on the spectrum analyzer from zero frequency up (or down) to the molecular feature to be measured. The scan rate was reduced to a lower value and the progress of the beatnote carefully monitored relative to the derivative signal. The TDL frequency was then locked to the desired point on the derivative signal which was displayed on the recorder. The beatnote was then averaged with the persistent screen averaging feature of the spectrum analyzer, and a marker oscillator was adjusted to the center of this averaged display. of the beatnote and the frequency modulation associated with the cold head and compressor generally precluded this approach. The next best approach is that described in the preceding paragraph.\u03bcm TDLs in a liquid helium Dewar) to 60 to 100 MHz (6 \u03bcm TDLs in a closed-cycle cooler) were observed during the measurements. However the larger values (in the 5 to 6 \u03bcm region) were observed prior to the currently implemented improvements in the vibration isolation system. The most recent approach was to adjust the current modulation for the derivative lock such that the beatnote linewidth was not broadened beyond the jitter linewidth. The best measurements were those made with a liquid helium Dewar; the beatnote was essentially stationary on the spectrum analyzer. However, the rapid He consumption rates for higher temperature TDLs made this choice impractical as well as inconvenient. When the compressor was used, the beatnote had a jitter linewidth associated with it and its frequency fluctuations made determination of the beatnote center more difficult. A wide variation of jitter linewidths from many different TDLs has been observed over an extended period. The current tuning rates (60 to 1600 MHz/ma) and linewidths due to current noise vary widely from one TDL to another. In a similar fashion the jitter linewidth varies greatly from one laser to the next, due to varying sensitivity to vibrations associated with the compressor/coldhead. Sometimes an apparent jitter linewidth was due to feedback, however this was generally recognized and steps were taken to minimize it. Beatnotes ranging in width from a few megahertz momentarily. The jitter-free beatnote was observed for a few seconds in this configuration. To date no appreciable deviation of the jitter-free beatnote from the marker oscillator has been observed.On some occasions, the beatnote envelope was slightly asymmetric. Generally, two different operators have determined the center value and some subjective disagreement was apparent. In a recent set of measurements of 20 transitions the average value of 10 measurements each from two operators varied by 2.5 MHz. This was well within the assigned uncertainty of 7 MHz for the measurement. More often, the average values from different operators agree within a fraction of 1 MHz.Another difficulty in these measurements was the presence of holes in the frequency coverage of the detector-rf-amplifier combination. In some instances, these frequency holes were associated with connector lengths and their effect could be minimized (by moving the hole to another frequency) by using line stretchers or by changing cables. Some holes were associated with lengths of connecting elements in the detector, and for practical purposes could not be eliminated. In other cases, holes were associated with amplifiers themselves; sometimes they precluded making measurements. In a few instances shallow holes have led to systematic errors. This occurred when only very weak TDL modes were available and the S/N for the beatnote was small (3 to 4 dB for example). Often the beatnote envelope was fairly wide (50 MHz or greater). In cases like these, one side of the beat-note envelope can overlap a hole and the apparent line center will be shifted. This has happened in a few instances but the error was apparent in the fitting process. In these cases, a repetition of the measurement with a different TDL and a much stronger beatnote gave a different and better fitting result. Such holes generally remain at the same frequency and experience has shown which frequency regions to avoid.2O and OCS transitions. This process required the use of the CO laser as a transfer oscillator, and the CO laser frequency was measured relative to a frequency generated by a CO2 laser synthesizer .Near the inception of this program, a CO laser stabilization scheme on low pressure CO laser discharges had been demonstrated by Freed [2.13]. More recently, a stabilization scheme using opto-galvanic detection has been reported by Schneider et al. [2.14]; neither of these schemes was operable over the entire range required for our measurements. Some values of CO frequencies in the literature (available when the measurements in this region began) were in error by over 50 MHz. Since the goal of this measurement program was to be able to make measurements with a 3 MHz uncertainty, it was necessary to measure the frequency of the CO laser at the same time that the CO laser-TDL difference frequency measurements were made on N\u22121 . The second CO laser was a flowing gas laser which was cooled by liquid-nitrogen and operated from 1220 to 1600 cm\u22121 (v = 36 to v = 20). After installation of a shorter wavelength grating and an appropriate output mirror, operation was extended to the 1900 to 2080 cm\u22121 region (v = 6 to v = 1). Additional details regarding the liquid-nitrogen cooled CO laser may be found in the literature .Two different CO lasers were used in this manner. One was a sealed-off laser which was cooled by flowing alcohol through dry ice and then through a jacket around the discharge tube. This operated over the frequency range from 1600 to 1900 cm1, in position for measuring the CO laser frequency relative to the CO2 synthesizer, which is shown enclosed in the large dashed box. The synthesizer consists of two stabilized CO2 lasers, a phase-locked microwave oscillator and frequency counter, a metal-insulator-metal (MIM) diode, and a combination of an rf amplifier, rf spectrum analyzer, and a 0 to 1.0 GHz rf frequency synthesizer. When radiation from the two CO2 lasers and the microwave oscillator were coupled to the MIM diode, currents were generated at a synthesized frequency, vs, given byv1 and v2 were the frequencies of the CO2 laser frequency standards, and vM was a microwave frequency. The quantities l, m, and n are integers which are allowed both positive and negative values. The quantity (l + |l| + |m| + |n|) is called the mixing order; the synthesized currents generally become weaker as the mixing order is increased. Mixing orders vary from 3 or 4 near 50 THz to 7 or 8 near 38 THz, the frequency at the longest wavelength operation of the CO laser used in these measurements. Typical values might be l = 3 or 4, m = \u2212 2 or \u22123, and (with the use of an X-band klystron) n was restricted to 0, \u00b11, or \u00b12.vCO, was generated in the diode and it combined with the synthesized frequency, vs, to produce a difference frequency beatnote at a frequency, vB1. The beatnote was amplified, displayed on the spectrum analyzer, and its excursion was noted as the CO laser was tuned through its gain bandwidth. The beatnote was positioned at the center of this excursion (a determination of the frequency of the CO transition was a secondary objective) and a marker signal from the rf synthesizer was used to mark this frequency point on the spectrum analyzer. The rf synthesizer reading was then used as the value for vB1 and the CO laser (which was not locked) was periodically readjusted to return the beatnote to the assigned frequency.When the CO laser radiation was focused on the MIM diode, an additional current at the CO laser frequency, 2 frequencies was used for the vs calculation. An uncertainty of 0.3 MHz in the transfer oscillator was included in the measurement uncertainty of the molecular transition, which was given byvB2 was the beatnote between the TDL and the transfer oscillator. The transfer oscillator frequency and beatnote frequency are both rounded to the nearest 0.1 MHz. The main uncertainty was again due to the TDL linewidth which was discussed in the early part of the chapter.The frequency of the CO laser (transfer oscillator) was thenv/dP, the pressure-induced frequency shifts, in the rovibrational spectrum of OCS. The potential for better absolute frequency measurements was also demonstrated.The most recent advance in making heterodyne frequency measurements with TDLs involves a computer-controlled, frequency offset-locking (CC-FOL) scheme. Freed et al. [2.16] demonstrated the use of a frequency offset lock combined with a frequency synthesizer to control the output frequency of the TDL. We have combined that technique with the scanning and data-logging technology used in this laboratory for other measurements [2.17\u20132.19] to obtain accurate data on d2 laser frequency standard were focused with separate lenses and then combined with a ZnSe beam splitter and directed to a HgCdTe heterodyne mixer/detector which produced a beatnote at the difference frequency, vB, between the two lasers. The beatnote was amplified in an rf amplifier and displayed on an rf spectrum analyzer. A balanced mixer was used to down-convert the beatnote at frequency vB to a nominal 160 MHz, the region of operation of the IF amplifier and discriminator. The beatnote was fed to one input arm of the balanced mixer, and the output of the sweepable frequency generator, at frequency vsw, was fed to the other input arm . The frequency vsw was adjusted such that |vsw\u2212vB| was nominally 160 MHz, and this resulting output signal was fed to the discriminator which had a sensitivity of 0.1 V/MHz and an 80 MHz bandwidth.vB was locked at a frequency vDO away from vsw That is,vDO is close but (due to the presence of various zero offsets in the locking loop) not necessarily equal to 160 MHz. For frequency shift and lineshape measurements, the important point is that the frequency vDO must remain fixed, whatever value it assumes. If a frequency measurement is the objective, it becomes necessary to measure vDO. Frequency of the CCFOL TDL is then given byvDO and make measurements with uncertainties the order of 0.2 MHz.After the switch in the loop filter was closed, the discriminator-based locking loop adjusted the TDL frequency to insure that the beatnote 2 laser transition because the lock loop requires a beatnote with a good S/N and the beatnote signal decreases with increasing frequency. This is also the band limit of our most convenient rf amplifier. We chose from the available TDLs those with sufficient power to give a beatnote with a S/N of about 30 dB. For the present measurements a 400 ms integration time was used and 640 points were recorded in each direction. Recording in both directions is a good way to cancel certain types of systematic errors. Generally only one round trip pass was made per measurement but as many passes could be made as required to give a good S/N.We have restricted our initial experiments to those OCS transitions which lie within 2000 MHz of a COA large number of measurements have been made with the older technique and these have been combined with FTS measurements, particularly the high quality measurements made recently. As the situation stands now good molecular constants exist, with the band centers currently having the largest uncertainties. The number of measurements left to be made is a relatively small number of high quality. The best approach is to make sub-Doppler or saturated measurements, however, the accidental overlaps required are rather infrequent. We believe the CCFOL approach is the next best option and several strategic overlaps occur in the 2 GHz range.2O. A brief description of their work and some related work concludes the summary of heterodyne techniques. It is of interest to compare and contrast some of the salient features of the TDL and the CCL. The tuning range of a TDL mode was 15 to 30 GHz; that of the CCL was less than 1 GHz. The linewidth of the TDL in the best instances was a few MHz, that of the CCL was 10 kHz. Perhaps the most important feature of the CCL was a large power output (in excess of 10 mW), which along with its beam quality permitted a direct coupling of the CCL output to the MIM diode, and subsequent synthesis measurements without a transfer oscillator. This relatively large power and narrow linewidth made it an ideal tool to use for some saturated absorption measurements by Pollock et al. on CO [5.304]. Sub-Doppler measurements could not be made on the N2O band studied, and uncertainties of 4 to 8 MHz (at 130 to 140 THz) were reported. This uncertainty was due to the uncertainty in locating the center of the transition and was due in part to the small free spectral range of the tuning element of the CCL, which frequently prevented us from sweeping over the entire line and was also insufficient to sweep far enough on either side of an absorption line to determine a background slope.Pollock et al. [5.219] used a color center laser (CCL) to perform a set of experiments on N+2)A center. The centers were optically pumped with the 3 W power output from an Nd:YAG laser operating in a TEM00 mode at 1.3 \u03bcm. These color centers were continuously replenished by uv radiation from an Hg lamp.Shown in Two Brewster\u2019s angle sapphire prisms, a single plate birefringent filter and one etalon comprised the tuning elements. The ring was constrained to operate in a unidirectional manner by an optical diode consisting of an AR-coated YIG plate in a 0.1 T magnetic field and a Brewster-cut quartz plate reciprocal rotator. One portion of the output radiation was used for stabilization to the side of a fringe in a passively stabilized optical cavity. The cavity was scanned by tuning a Galvo plate inside this reference cavity. Corrections were applied to the Galvo plate (slow) and to the PZT driving the tuning mirror (fast) in the laser resonator; this narrowed the CCL linewidth to 10 kHz. A second portion of the beam was split off and sent through a cell containing CO. The Galvo plate in the reference cavity was modulated at 7 kHz and slowly scanned to observe the first derivative signal, which was used to lock the CCL to the CO lines of interest.2 synthesizer for a simultaneous measurement of the CO frequency. Typical synthesis schemes used 5v1, 4v1 + v2, or 3v1+ v2, where v1 and v2 are different CO2 laser frequencies. No microwave oscillators were required, and the vB1 type beatnotes fell within 2 GHz. In contrast to the TDL measurements, the measurement uncertainty was entirely the uncertainty in locating the center of the absorption line.A third portion of the CCL radiation was directed to the CO4 and the 9.33- and 10.18-\u03bcm transitions in CO2, Appl. Phys. Lett. 22, 192\u2013196 (1973).[2.1] K. M. Evenson, J. S. Wells, F. R. Petersen, B. L. Danielson, and G. W. Day, Accurate frequencies of molecular transitions used in laser stabilization: the 3.39-\u03bcm transition in CH2 10.6-\u03bc transitions observed in a low pressure room temperature absorber gas, Appl. Phys. Lett. 17, 53\u201356 (1970).[2.2] C. Freed and A. Javan, Standing-wave saturation resonances in the CO22, 196\u2013199 (1973).[2.3] R. L. Barger and J. L. Hall, Wavelength of the 3.39-\u03bcm laser saturated absorption line of methane, Appl. Phys. Lett. 29, 1346\u20131349 (1972).[2.4] K. M. Evenson, J. S. Wells, F. R. Petersen, B. L. Danielson, G. W. Day, R. L. Barger, and J. L. Hall, Speed of light from direct frequency and wavelength measurements of the methane-stabilized laser, Phys. Rev. Lett. 12C16O2 lasers stabilized by saturated absorption, Laser Spectroscopy, (ed. Brewer and Mooradian) Plenum Press, pp. 555\u2013569 (1974).[2.5] F. R. Petersen, D. G. McDonald, J. D. Cupp, and B. L. Danielson, Accurate rotational constants, frequencies and wavelengths from 92, 11\u201316 (1987).[2.6] D. A. Jennings, R. E. Drullinger, K. M. Evenson, C. R. Pollock, and J. S. Wells, The continuity of the meter: the redefinition of the meter and the speed of light, J. Res. Natl. Bur. Stand. (U.S.) [2.7] C. R. Pollock, D. A. Jennings, F. R. Petersen, J. S. Wells, R. E. Drullinger, E. C. Beaty, and K. M. Evenson, Direct frequency measurements of transitions at 520 THz (576 nm) in iodine and 260 THz (1.15 \u03bcm) in neon, Opt. Lett. 3, 133\u2013135 (1983).2 stabilized He-Ne 473 THz (633 nm) laser, Opt. Lett. 3, 136\u2013138 (1983).[2.8] D. A. Jennings, C. R. Pollock, F. R. Petersen, R. E. Drullinger, K. M. Evenson, J. S. Wells, J. L. Hall, and H. P. Layer, Direct measurement of the I12C16O2, J. Mol. Spectrosc. 102, 112\u2013122 (1983).[2.9] F. R. Petersen, E. C. Beaty, and C. R. Pollock, Improved rovibrational constants and frequency tables for the normal laser bands of 2 isotopic species, IEEE J. Quant. Elect. QE-22, 234\u2013267 (1986).[2.10] L. C. Bradley, K. L. Soohoo, and C. Freed, Absolute frequencies of lasing transitions in nine CO13CO2 laser hot band transitions, Appl. Opt. 20, 3635\u20133640 (1981).[2.11] F. R. Petersen, J. S. Wells, A. G. Maki, and K. J. Siemsen, Heterodyne frequency measurements of 12C16O2 laser hot band transitions, J. Mol. Spectrosc. 105, 324\u2013330 (1984).[2.12] F. R. Petersen, J. S. Wells, K. J. Sicmsen, A. M. Robinson, and A. G. Maki, Heterodyne frequency measurements and analysis of QE-9, 219\u2013226 (1973).[2.13] C. Freed and H. A. Haus, Lamb dip in CO lasers, IEEE J. Quant. Elect. B44, 241\u2013245 (1987).[2.14] M. Schneider, A. Hinz, A. Groh, K. M. Evenson, and W. Urban, CO laser stabilization using the optogalvanic Lamb-dip, Appl. Phys. 107, 48\u201361 (1984).[2.15] J. S. Wells, D. A. Jennings, and A. G. Maki, Improved deuterium bromide 1-0 band molecular constants from heterodyne frequency measurements, J. Mol. Spectrosc. 438, 119\u2013124 (1984).[2.16] C. Freed, J. W. Bielinski, and W. Lo, Programable secondary frequency standard based infrared synthesizer using tunable lead-salt lasers, Proc. SPIE 44, 576\u2013578 (1984).[2.17] K. M. Evenson, D. A. Jennings, and F. R. Petersen, Tunable far-infrared spectroscopy, Appl. Phys. Lett. B48, 311\u2013313 (1989).[2.18] D. A. Jennings, The generation of coherent tunable far infrared radiation, Appl. Phys. 2 rotational line at 60.46 cm\u22121, Geophys. Res. Lett. 14, 722\u2013725 (1987) and \u201cCorrection: Air- and oxygen-broadening coefficients for the O2 rotational line at 60.46 cm\u22121, Geophys. Res. Lett. 14, 981 (1987).[2.19] D. A. Jennings, K. M. Evenson, M. D. Vanek, I. G. Nolt, J. V. Radostitz, and K. V. Chance, Air- and oxygen-broadening coefficients for the O+2)A Color Centers, Appl. Phys. B28, 308\u2013309 (1982).[2.20] C. R. Pollock and D. A. Jennings, High Power cw Laser Operation Using and J = 0 is not allowed and for J < 3 only the central two-by-two matrix is allowed. Higher order terms coupling l and l \u00b1 4 levels are sometimes important but were not necessary for the present calculations.For l-type resonance calculation requires the use of a matrix of dimension v2 +1 by v2 + l. Since this is a nonlinear system, a nonlinear least-squares fitting technique was needed to fit the experimental data to determine the best constants, as explained later.In general the 2O. That has the effect of absorbing the l-type resonance into the effective Bv, Dv, and Hv values. While such a treatment is quite reasonable, the effective values of the higher order constants are quite different from the ground state values, and the level at which l-type resonance explicitly, we bring the effective values for Dv and Hv much closer to the ground state values. This model gives a better approximation to the true Hamiltonian than the model that only uses Most other workers have only used l| (except l = 0) the states with v2 > 0 are split into e and f components. For OCS and N2O the l = 0 states (1+\u2211 states) always have the same symmetry (or parity) as the e states. These e and f components have been assigned in accordance with the convention established by Brown et al. [3.3]. That convention leads to the selection rules:\u0394l = 0, \u00b1 1, is broken because perturbations always connect e to e and f to f.For each value of |l-type resonance energy matrices, like f levels in the other case. We have used the full matrix, as indicated by All of the v1, v2 + 2,l, v3 \u2212 1,J) and of OCS and N2O. In OCS the unperturbed Fermi resonance levels are far apart, so there is very little change in the resonance across a band. This results in only small changes in the effective values of Dv, Hv, and Lv. Such small changes can be accommodated by 2O the Fermi resonance is expected to be more important but again the effective values of Dv, Hv, and Lv are only slightly changed from the unperturbed values.The present analysis ignores the Fermi resonance that couples the levels was then determined by the double summation,ijV is a particular element of the variance-covariance matrix and \u2202v/i\u2202c and \u2202v/j\u2202c are the derivatives of the transition frequency with respect to the rovibrational constants ic, and jc respectively.In order to calculate the statistical uncertainties in the calculated wavenumbers given in these tables it was necessary to use the variance-covariance matrix, given by the least-squares analysis, and the derivative of the transition frequency with respect to each constant. The uncertainty, or estimated standard error, given by All of the OCS transitions to be used for calibration (shown with an asterisk in the atlas) were calculated by means of constants and a variance-covariance matrix given by a single least-squares fit that included all of the frequency measurements given in the literature. The equations used in this fit were described in the preceding section. In this section we indicate what references provided the data that went into that fit and give a few more details about the fit and the selection of data.The rotational spectrum of OCS has been extensively studied by microwave and sub-millimeter wave techniques. These measurements use frequency techniques for calibration and have uncertainties on the order of \u00b1 0.05 MHz and in some cases even smaller uncertainties. Such measurements are blessed with small line widths and are made at low pressures which contribute to the accuracy of the measurements. The three most abundant isotopic species of OCS have no fine structure due to quadrupole effects.J values so they are able to give accurate values for Bv and Dv. In addition, the heterodyne measurements made by Vanek et al. [5.124] on high-J transitions were used in the analysis. Although there are a great many measurements of rotational transitions for the lower vibrational states, Bogey and Bauer [5.78] and Tanaka et al. [5.98] have given measurements of rotational transitions for fairly high vibrational states, up to 4100 cm\u22121. Some transitions show the splitting due to 1-type resonance and for a few vibrational states, 0110 , 0220 [5.54], and 0310 [5.54], the transitions between split levels have been observed.Some microwave measurements extend to fairly high Altogether 333 frequency measurements of rotational transitions, taken from the above references as well as from Refs. , were included in the least-squares fit that determined the rovibrational constants given in 00-0000 band and accompanying hot bands made in the Harry Diamond Laboratory by Sattler et al. [5.88], the measurements in the same frequency region made at the University of Lille by Fayt et al. [5.126], and the preliminary measurements from the University of Bonn [5.137a]. From the root-mean-square (rms) deviations of the NIST measurements it was obvious that their assigned uncertainties were too large by approximately a factor of two. This reflected caution in allowing for systematic errors which would not be revealed by the least-squares analysis.With three exceptions, all of the infrared heterodyne frequency measurements came from a series of papers from the same laboratory at the National Institute of Standards and Technology in Boulder, Colorado . The exceptions are the measurements on the 02An extensive set of laser-Stark resonance measurements have been made by Fayt and others and by Tanaka et al. . This is a type of frequency measurement that should be quite accurate but we have not included those data in this least-squares fit as they would introduce the additional complications of determining dipole-moment functions and assessing the accuracy of the electric field measurements. In the case of measurements using CO laser transitions there is an additional uncertainty in the laser frequency.In order to determine the most accurate centrifugal distortion constants, some of the better diode laser and FTS measurements were included in the least-squares fits. For the most part the diode laser measurements given in Refs. were calibrated with the heterodyne measurements and probably had systematic errors much smaller than the dispersion shown by the least-squares fit.Except for the weakest transitions, the FTS measurements were more precise than any of the other infrared measurements. The high precision, however, does not necessarily imply high accuracy. The FTS data used in the analysis for these tables were taken from Refs. or from private communication with the authors of those papers in the cases where the original data were not published.The FTS measurements were given uncertainties equal to the rms deviations of the fits on a band-by-band basis. In order to keep the FTS measurements from affecting the determination of the vibrational energy levels, they were fitted to the same rotational constants as the other data, but to different band centers. All of the recommended calibration data were based on vibrational energy levels determined only from frequency measurements, not from FTS or ordinary diode-laser measurements.16O13C32S and 16O12C34S have enough frequency measurements to warrant being considered as possible calibration transitions. In most cases, however, transitions of the rarer isotopomers are only included in the atlas to help in identifying the other, more useful transitions.For the less abundant isotopomers of OCS many of the above papers plus a few additional papers give microwave and sub-millimeter wave measurements of rotational transitions. Some of the infrared heterodyne measurements also included transitions for the less abundant isotopomers of OCS . A few transitions of A good many wavelength measurements have been made on the less abundant isotopomers, and they can be found in the bibliography, Sec. 5. The most important sources of information on infrared measurements of the less abundant species are Refs. .2O are not so extensive as for OCS but a great many measurements are still available. The early work of Pearson et al. [5.161] and of Lafferty and Lide [5.156] were very useful as were other early measurements given in the review by Lovas [5.5], namely the data given in Refs. . The v1 rotational transitions given by Bogey [5.186] and the high-J transitions given by Andreev et al. [5.194], by Burenin et al. [5.179], and by Vanek et al. [5.242] were of particular value for better determining the centrifugal distortion contribution to the line positions.The microwave data on N2O have come from two laboratories, NRC in Canada, and NIST in the United States. The only saturated absorption measurements were those of Whitford et al. [5.183] on the laser transitions, 1000-0001, near 930 cm\u22121. The other infrared heterodyne measurements were made by Wells and co-workers in a series of papers, Refs. .All of the heterodyne measurements involving N2O using either grating instruments or, more recently, FTS instruments. Some of the more important measurements which were used in the least squares refinement of the constants, but did not contribute to the band centers for the recommended calibration lines, were given in Refs. .There have been a great many measurements on infrared bands of NAll these data were fit in the same way as was done for OCS. The constants given by the least-squares fit are given in 2O the Fermi resonance is much more important than for OCS; nevertheless, the Fermi resonance was ignored in the fits and only the l-type resonance was included in the analysis. For some levels the Fermi resonance causes an effective centrifugal distortion quite different from that of the ground state.For NIn order to show the position of some of the hot band lines in the spectra, it was necessary to use constants for some levels not included in 15N14N16O and 14N15N16O [5.231]. For the most part the data for the rarer isotopic species were taken from Refs. .For the less abundant isotopic species, the microwave data given in Refs. were used in preparing these tables. One paper has reported heterodyne frequency measurements in the infrared for 2) is a symmetric linear molecule, it is nonpolar and has no microwave spectrum. There are, however, several high resolution infrared studies of its spectrum in the 1450 to 1550 cm\u22121 region in addition to the heterodyne measurements made by Wells et al. [5.390]. A number of other measurements have been made on CS2 so that the ground state constants, B0 and D0, are quite well determined for both the 12C32S2 and 13C32S2 isotopic species.Since carbon disulfide calibration. There are a few frequency measurements for the other isotopomers, but not enough to provide good calibration.The carbon monoxide (CO) wavenumbers for the calibration lines given in the atlas were calculated from the constants given in 12C16O molecule the ground state constants are primarily based on the sub-millimeter wave measurements given by Gordy and Cowan [5.250], Rosenblum et al. [5.253], and Helminger et al. [5.266] and on the far-infrared heterodyne measurements of Nolt et al. [5.309] and Varberg and Evenson [5.320]. Also included in the fit were microwave measurements of the J = 1\u21900 transitions in the first two vibrationally excited states as reported by Dixon [5.288]. Aside from these two measurements the upper state constants are based primarily on the heterodyne measurements of the 1-0 band given by Schneider et al. [5.314] and by Maki et al. [5.316] and the 2-0 band given by Pollock et al. [5.304]. Also used was one sub-Doppler measurement of the 1-0 band communicated to us by Urban [5.321].For the v = 1, 2, and 3 states. Only heterodyne frequency measurements were used to determine the vibrational frequencies.Other data included in the analysis to determine the best constants were some heterodyne laser measurements given by Schneider et al. [5.313] and some FTS measurements from Guelachvili et al. and Brown and Toth [5.306]. The FTS measurements were used to help determine the best centrifugal distortion constants for the Y10, Y20, Y01, Y11, Y21, Y02, Y12, and Y03 were fit to data for only the v = 0, 1, and 2 states. The other constants were constrained to values given by earlier fits which included data for higher vibrational states, as described by Schneider et al. [5.314].The analysis of the CO data was carried out in the same way as described by Maki et al. [5.316] except that new data have been included . In order to avoid the possibility of problems with the potential function model, the lowest order constants, The uncertainties given for the calibration wavenumbers are based on the variance-covariance matrix given by the least-squares fit with the higher order constants constrained.12C16O species. The wavenumbers for the rarer isotopic species are given to help in correctly identifying the calibration lines.The wavenumbers for the other isotopic species of CO were calculated from constants given by Guelachvili et al. [5.301], but corrected to agree with the offset observed in the wavenumbers for the 14N16O species. The constants given by Amiot and Guelachvili [5.355] were used for 15N16O and those given by Amiot et al. [5.350] were used for 14N18O Those were the only transitions strong enough to show on the spectral plots. The uncertainties given in the tables are only estimates based on the accuracy of other heterodyne measurements and an estimate of the accuracy of the Hamiltonian used to fit the data.The wavenumbers of the line positions used to produce the NO atlas were calculated using the constants given by Hinz et al. [5.371] for the 14N16O. Because only one paper [5.371] reports infrared frequency measurements for NO, the NO lines are not recommended for calibration in those regions where either OCS or N2O transitions are available for calibration. For many spectrometers most of the NO transitions are unresolved doublets. At low pressures the doublets will have equal intensities and widths so that no appreciable errors will be incurred by using the average frequency of the doublet. A few of the low-J transitions, especially for the Q-branch lines, will have additional structure due to the interaction of the nuclear electric quadrupole moment of the nitrogen atom with the surrounding charge distribution. Such small splittings will be no larger than a few megahertz and the average line positions given in the tables will not be affected.The tables only give the wavenumber values for lines of This section is intended to show how the transition intensities were calculated and how the intensity was defined. This will enable users to determine the intensity to be expected for conditions other than those used to prepare the atlas. In order to estimate the appearance of the spectrum under conditions of pressure broadening and spectrometer resolution different from that used to produce the atlas figures, it is also necessary to consider the line shapes and the effect of finite slit functions. Such effects are discussed in Sec. 4.S, to meank(v) is the absorption coefficient at frequency v, p is the partial pressure of the gas, l is the length of the absorption path, I0 is the intensity of radiation without absorption from the line in question, and I is the intensity of radiation after absorption by the line. Note that The integrated intensity of an individual line representing a single rovibrational transition is independent of the line shape. For this atlas we take the integrated line intensity, C is a proportionality constant that includes the factors 8\u03c03/3hc and other factors, such as the Loschmidt constant (2.686 763 \u00d7 1025 molecules/m3), required to give S in appropriate units. If S is in units of cm/molecule at STP, C is 4.162 38 \u00d7 10\u221219 cm2 D\u22122/molecule. If S is in units of cm\u22122 atm\u22121 at temperature T, C would be 3054.7262/T cm\u22121 D\u22122 atm\u22121. In \u221230C m), v is the transition wavenumber in units of cm\u22121, T is the temperature in kelvin, Ni is the concentration of the isotopic species under consideration, Qv and QR are the vibrational and rotational partition functions respectively, and Sv and SR are vibrational and rotational strength factors that should be included in the intensity. Some workers prefer to include SV in the transition moment but we prefer to express it separately so the transition moment can be seen to be nearly the same for the ground state transitions and the accompanying hot bands. SR is also called the direction cosine matrix element. The intensities given in these tables were calculated for a temperature of 296 K.The integrated intensities, as given in this atlas, were calculated by using the equationNi/QvQR compensates for the fact that the pressure used in Ni were calculated from the isotopic abundances given in In The rotational partition functions were calculated from the equations given by McDowell [3.7]. A different rotational partition function was calculated for each vibrational energy level and for each isotopomer.S0 = S/Ni for 5 because S0 seems to be a more appropriate molecular property. On the other hand, S is more useful for analytical purposes, such as the determination of the amount of CO in the atmosphere. Actually, it is |R| or |R|2, rather than S, that is the true molecular property in R|, or |R|2. Unfortunately, some authors have left out the Ni term and report values of |R| that are not true molecular properties relatable to the electron distribution in the molecule.Some workers like to use In the infancy of infrared spectroscopy the instrumentation was unable to resolve individual rovibrational transitions, so many early papers measured the intensity of entire vibrational bands. Those papers measured band intensities by using a modification of Ni/QVQR are all omitted and v is set equal to the center of the band. This band intensity will generally be within a few percent of the intensity obtained by adding all the line intensities for the band. To be faithful to the original meaning, the true band intensity should be the sum of the intensities of all the lines in the band, including all isotopes and all hot bands.From those early measurements the term band intensity came to mean the intensity of all the lines in a band including all isotopes present in a normal sample and all hot bands. As a first approximation such a band intensity can be calculated from \u0394v2. For simplicity the strength factor was broken into two factors such that\u0394v2 even (or zero)\u0394v2 oddS2 = 0 if |\u0394l| > 1. In v\u2032 and v\u2033 is used for v, \u0394v = |v\u2032 \u2212 v\u2033|, l = l\u2033, and \u0394l = l\u2032 \u2013 l\u2033. For the present calculations, S2 can be taken as the positive square-root of The vibrational strength factors were slightly different for even and odd values of v1 \u2212 v1, v1 \u2212 v1, SV in the transition moment, |R|, in which case the transition moment for certain hot bands will be very different from the transition moment for the ground state transitions.Note that v2 = 0 (and l = 0) the rotational strength factors are given bym has the usual meaning of \u2212J\u2033 for \u0394J = \u22121 and J\u2033 + l for \u0394J = +1.For transitions for which v2 \u2260 0, the l-type resonance energy matrix was used and the intensity was obtained by multiplying each term of the eigenvector, for the appropriate eigenvalue, by the appropriate intensity factor given by SVSR where SR was determined from Table 2.1 of Gordy and Cook [3.11], or Table 4-4 of Townes and Schawlow [3.12]. Di Lauro and Mills [3.13] describe a similar procedure for determining intensities of transitions in Coriolis coupled levels of a symmetric rotor. For the specific cases of l-type resonance, this procedure was described by Maki et al. [3.14] although they dealt with the symmetry factored matrix whereas the present calculations used the unfactored matrix, such as If v1, v2, l, v3, J) to an upper state that is involved in l-type resonance, = . The upper state energy is given by a particular eigenvalue, E1. The eigenvector for this eigenvalue gives the mixing coefficients \u03b111, \u03b112, \u03b113, etc. that measure the contribution of each unperturbed state to the perturbed state. The transition intensity is given byl\u2032 values. The l-type resonance mixes levels that differ only in the value of l.To understand this intensity calculation let us consider a transition from an unperturbed lower state as determined from adding all the line intensities including hot bands and different isotopes. This may be compared to the value 9.55 \u00d7 10\u221217 cm/molecule given by McKean et al. [5.378], 9.38 \u00d7 10\u221217 cm/molecule given by Robinson [5.375], 9.23 \u00d7 10\u221217 cm/molecule given by Kiyama and Ozawa [5.377], and 9.13 \u00d7 10\u221217 cm/molecule given by Person and Hall [5.379].Only a few intensity measurements have been made on the \u22121 it is difficult to determine which measurements are best but most of the recent measurements give integrated band intensities close to 1.027 \u00d7 10\u221217 cm/molecule (276 cm\u22122 atm\u22121 at 273.15 K). For this atlas we have used a dipole transition moment of 0.1073 D which gives a total band intensity of 1.03 \u00d7 10\u221217 cm/molecule (276 cm\u22122 atm\u22121 at 273.15 K or 255 cm\u22122 atm\u22121 at 296 K). The changes in the matrix elements for the less abundant isotopic species were taken from the theoretical calculations of Chackerian and Tipping [5.305]. The isotopic abundance was taken from \u221217 cm/molecule) are in agreement with other recent measurements for the main isotopic species and they also have studied the intensity of the weaker isotopic transitions. They gave transition intensities calculated from the electric dipole moment function given by Chackerian and Tipping [5.305]. Their calculated intensities seem to include a weak Herman-Wallis effect but they do not give any explicit constants for easily calculating that effect. A calculation that duplicates their temperature and dipole derivative agrees with their values to within one percent (for J < 35) even without including a Herman-Wallis effect.Because of the large spacing between lines, CO was one of the first molecules for which individual line intensities were measured [5.255]. More recent measurements are tabulated in the review article by Smith et al. [5.2]. For the fundamental band near 2143 cmIn an earlier paper [5.282] Tipping gave calculated values for the Herman-Wallis constants but they were small enough to ignore for this atlas. Bouanich [5.310] has also given calculated values for the Herman-Wallis constants. Apparently there are only two experimental determinations of Herman-Wallis constants that have been reported for the fundamental band of CO . The earlier work is subject to question because of the sensitivity to temperature errors. The most recent measurement was reported after this work was done and would change the intensities by no more than one percent. The intensity calculations used for the atlas did not include a Herman-Wallis effect for the fundamental band.\u22121. A good average of the more recent values seems to give an integrated band intensity of 7.78 \u00d7 10\u221220 cm/molecule (2.09 cm\u22122 atm\u22121 at 273.15 K) with an uncertainty of about 6 percent. This is equivalent to a transition dipole matrix element of 0.0066 D.Fewer intensity measurements have been made on individual lines of the overtone band near 4260 cmC1 = 0.005 and C2 = 0.000 034 [see The Herman-Wallis effect is significant for the first overtone band and has been included in the intensity calculation for the atlas. The constants given by Tipping [5.282], 034 see , were us\u221218 cm/molecule (125 cm\u22122 atm\u22121 at 296 K) which agrees with the measurements of King and Crawford [5.330], Mandin et al. [5.359], and Holland et al. [5.368]. Some earlier measurements and even some recent measurements [5.374] indicate that the intensity might be more like 4.44 to 4.64 \u00d7 10\u221218 cm/molecule (110 to 115 cm\u22122 atm\u22121 at 296 K) so the intensities given in the tables may be too large by about 10 percent. We have taken the higher intensity value because NO is prone to having impurities that are hard to remove, thus giving low intensity readings.A transition moment of 0.00412 D was used to calculate the line intensities given in the tables. This gives an integrated band intensity of about 5.04 \u00d7 10Smith et al. [5.2] have given a good discussion of lineshapes and the determination of pressure broadening coefficients. We shall give here only a brief description to ensure that the reader understands the principal equations describing these effects. For a more complete understanding of the subject one should refer to the work of Smith et al. [5.2] and the papers to which they refer.For a static gas in a field-free environment at pressures below one atmosphere, there are four major factors that might contribute to the shapes of infrared absorption lines, 1) lifetime broadening, 2) Doppler broadening, 3) pressure broadening, and 4) collisional narrowing.n is given byn\u03b3 is the half-width of the state and \u03c4n is the lifetime of that state. For a transition i \u2192 j between two states, i and J, the transition linewidth will be given by the lifetime of both upper and lower states,\u22128 cm\u22121 (0.16 kHz) or less. This is much smaller than the Doppler width even at temperatures on the order of 5 K. For Doppler-free measurements the effect of lifetime broadening could be important even for stable molecules although various instrumental effects, such as beam width or beam collimation, usually limit the effective linewidth. Transit time broadening is a variation of lifetime broadening where the lifetime is the time that the molecule is in the light-beam.The lifetime broadening of a state v is the wavenumber or frequency of the transition, T is the temperature of the gas in kelvin, M is the relative molecular mass of the molecule in atomic mass units, and \u03b3D is half the width of the transition at half the intensity . Since spectrometer resolution is often expressed in terms of the full width at half the line height (FWHH), the Doppler width is sometimes given by 2\u03b3D.The Doppler width is the result of the random motion of the molecules in a gas sample and is given byv0 is the frequency (or wavenumber) of the center of the line.For most gases at ambient temperatures and pressures below 2 kPa (15 Torr), the true lineshape is dominated by the Doppler effect. For some molecules the effect of collisional narrowing, see below, is also important in that pressure regime. The Doppler effect gives a Gaussian lineshape which is described by the functionf(v) has been normalized so thatk(v) is the absorption coefficient at frequency v and S is the integrated line intensity given earlier in In One important characteristic of the Gaussian lineshape is the small wing absorption due to the exponential reduction in absorption as one gets farther from the center of the line. As pointed out by Korb et al. [5.263], accurate intensity measurements are more easily made when the wing absorption is small. Another characteristic of the Gaussian shape is the bluntness at the center of the line.\u03b3L is half the width of the line at the half intensity point. When pressure broadening is the dominant effect determining the lineshape, then Pressure broadening gives rise to lines with a Lorentzian lineshape for which the normalized shape function has the formxP, of that gas. The total broadening in a mixture is the sum of the broadening of each gas. Thus, for gases a and b with broadening coefficients ca and Cb, the total pressure broadened width will be \u03b3L = caPa + cbPb. The broadening coefficient is unique to each absorbing molecule and to each collision partner. The broadening coefficient is a function of the temperature as one might expect since the average collision velocity changes with temperature. The broadening coefficient is also different for each rotational transition although the changes are systematic with the rotational quantum numbers.Pressure broadening is an additive effect, therefore, the broadening of each gas in a mixture depends only on the partial pressure, The pressure broadening coefficients generally have values in the range of 400 to 1300 MHz/Pa (3 to 10 MHz/Torr) and are greatest for molecules that have large dipole moments. The pressure broadening coefficients are generally smallest for those rotational energy levels that are at relatively high energy.In contrast to Gaussian shaped lines, the Lorentzian shaped lines are sharper at the line center but have very extensive wings. For very strong lines it is possible to have significant absorption intensity twenty half-widths from the line center. This is noticeable in the CO atlas where there is only a small amount of pressure broadening and yet the strong lines have very noticeable wings. If there were no pressure broadening, the wings of the strong lines would not be so prominent.In many cases the lineshape is determined both by the Doppler effect and by the effects of pressure broadening. In such cases the lineshape is more accurately given by a Voigt profile which is a convolution of the Gaussian and Lorentzian profiles. There is no good single closed-form expression for the Voigt profile. Rather, the Voigt shape function is given by the integral expression\u03b3D. In other words, it makes the line appear to have a Doppler width that is smaller than that calculated by Collisional narrowing or Dicke narrowing [3.19\u20133.21] has only recently been measured for a few molecules, but its effects have been observed for NO [5.370]. Collisional narrowing has the effect of reducing the size of the Gaussian linewidth From tables of line intensities, such as are given in this atlas, it is possible to estimate the pressure-pathlength product needed to obtain a spectrum with adequate intensity. For this purpose we consider the two limiting cases of Doppler (or Gaussian) shaped lines at low pressures and the pressure broadened Lorentzian lines for high pressures.C is 1.1494 \u00d7 1014 if S is the intensity given in the tables (in units of cm/molecule), \u03b3 is the Doppler width found a pressure shift (due to CO) on the order of \u22122\u00b11.5 kHz/Pa (\u22120.3 \u00b1 0.2 MHz/Torr). Bouanich [5.302] found pressure shifts on the order of \u22121.2 \u00b1 0.3 kHz/Pa (\u22120.16 \u00b1 0.04 MHz/Torr). He seems to have observed a significant rotational dependence, but we only quote an average value. For the overtone of NO, Pine et al. [5.370] found a self-induced pressure shift of \u22121.1 \u00b1 0.3 kHz/Pa (\u22120.15 \u00b1 0.04 MHz/Torr). They found that there may be a weak rotational dependence but it was obscured by experimental error.2O an attempt to measure the self-induced pressure shift in the rotational spectrum resulted in an estimate of an upper limit of 0.75 kHz/Pa [5.201]. The pressure shift of several lines of N2O were measured near 4500 cm\u22121 and an average value of \u22121.2 \u00b1 0.3 kHz/Pa (\u22120.16 \u00b1 0.04 MHz/Torr) was found [5.219]. The pressure shift caused by N2 and O2 on the v3 band of N2O near 1280 cm\u22121 was measured by Varanasi and Chudamani [5.238]. Their diode laser measurements gave an average value of about \u22120.6 \u00b1 0.15 kHz/Pa (\u22120.08 MHz/Torr) for several lines between 1250 and 1300 cm\u22121.For N\u22121 [5.133] indicate that the self-shift is \u22120.37 \u00b1 0.04 kHz/Pa (\u22120.049 + 0.005 MHz/Torr). Recent measurements of the self-shift of microwave transitions [5.119] found that the shift was too small to measure, 0.000 \u00b1 0.04 kHz/Pa or 0.000 \u00b10.006 MHz/Torr.More pressure shift measurements seem to have been made on OCS than on any of the other molecules in this atlas. The earlier measurements indicated that the pressure shift was on the order of 4.0 kHz/Pa (0.5 MHz/Torr) or less [5.94]. Later this estimate was improved by new measurements that gave an average value of \u22120.4 \u00b1 1.5 kHz/Pa (\u22120.05 \u00b1 0.20 MHz/Torr) [5.120]. The most recent measurements at about 1000 cm2 laser lines near 1000 cm\u22121. They found the shift to be on the order of \u22121.05 \u00b1 0.2 kHz/Pa (\u22120.14 \u00b1 0.03 MHz/Torr) with no evidence of a J-dependence. One might expect that the self-induced pressure-shift of CO2 would be similar to that of the molecules used in the present compilation.Kou and Guelachvili [3.23] have recently measured the self-induced pressure shift for the COSince the pressure shift is a shift in the energy levels, it is likely to be greater as one goes to higher energy levels. As a first approximation one can probably assume that the shift is proportional to the frequency. It is also possible that for polyatomic molecules, the pressure shift may depend, to a large extent, on the vibrational mode involved.2O, NO, CO, and CS2 should be increased by 0.3 MHz unless the pressure shift is added to the frequencies given in these tables or unless more accurate values for the pressure shift become available. For OCS the uncertainty should be increased by about 0.1 MHz/Torr. Note that the pressure shift seems to be negative for all the molecules in this atlas.For purposes of estimating the maximum error that could be introduced in a calibration measurement using any of the data given in this atlas, one should treat the frequencies given in this work as applying for a pressure below 130 Pa (1 Torr). For each increase in pressure of 130 Pa (1 Torr) the uncertainty in the frequency for N41, 721\u2013731 (1932).[3.1] J. L. Dunham, The energy levels of a rotating vibrator, Phys. Rev. l-type resonance doublets, J. Chem. Phys. 47, 3206\u20133210 (1967).[3.2] A. G. Maki and D. R. Lide, Microwave and infrared measurements on HCN and DCN: observations on 55, 500\u2013503 (1975).[3.3] J. M. Brown, J. T. Hougen, K.-P. Huber, J. W. C. Johns, I. Kopp. H. Lefebvre-Brion, A. M. Merer, D. A. Ramsay, J. Rostas, and R. N. Zare, The labeling of parity doublet levels in linear molecules, J. Mol. Spectrosc. 56, 163\u2013165 (1975).[3.4] W. F. Rowe and E. B. Wilson, An Application of the Hellmann-Feynman Theorem to vibration-rotation interactions, J. Mol. Spectrosc. 56, 696\u2013768 (1984).[3.5] H. S. Peiser, N. E. Holden, P. De Bievre, I. L. Barnes, R. Hagemann, J. R. DeLaeter, T. J. Murphy, E. Roth, M. Shima, and H. G. Thode, Element by element review of their atomic weights, Pure Appl. Chem. 13, 809\u2013891 (1984).[3.6] P. De Bievre, M. Gallet, N. E. Holden, and I. L. Barnes, Isotopic abundances and atomic weights of the elements, J. Phys. Chem. Ref. Data 88, 356\u2013361 (1988).[3.7] R. S. McDowell, Rotational partition functions for linear molecules, J. Chem. Phys. [3.8] E. B. Wilson, J. C. Decius, and P. C. Cross, Molecular Vibrations\u2014The Theory of Infrared and Raman Vibrational Spectra, McGraw-Hill Book Co, Inc., New York, 1955.106, 1195\u20131200 (1957).[3.9] W. Moffitt and A. D. Liehr, Configurational instability of degenerate electronic states, Phys. Rev. 61, 272\u2013281 (1976).[3.10] R. H. Tipping, Vibration-rotation intensities for Hot bands, J. Mol. Spectrosc. [3.11] W. Gordy and R. L. Cook, Microwave Molecular Spectra, John Wiley and Sons, New York, 1970.[3.12] C. H. Townes and A. L. Schawlow, Microwave Spectroscopy, McGraw-Hill Book Co., New York, 1955.21, 386\u2013413 (1966).[3.13] C. Di Lauro and I. M. Mills, Coriolis interactions about X-Y axes in symmetric tops, J. Mol. Spectrosc. 36, 433\u2013447 (1970).[3.14] A. G. Maki, W. B. Olson, and R. L. Sams, HCN rotational-vibrational energy levels and intensity anomalies determined from infrared measurements, J. Mol. Spectrosc. 23, 637\u2013646 (1955).[3.15] R. Herman and R. F. Wallis, Influence of vibration-rotation interaction on line intensities in vibration-rotation bands of diatomic molecules, J. Chem. Phys. 36, 404\u2013413 (1970).[3.16] R. H. Tipping and R. M. Herman, Line intensities in HBr vibration-rotation spectra, J. Mol. Spectrosc. 5, 549\u2013552 (1965).[3.17] C. Young, Calibration of the absorption coefficient for lines with combined Doppler and Lorentz broadening, J. Quant. Spectrosc. Radiat. Transfer 16, 611\u2013614 (1976).[3.18] S. R. Drayson, Rapid computation of the Voigt profile, J. Quant. Spectrosc. Radiat. Transfer 89, 472\u2013473 (1953); J. P. Wittke and R. H. Dicke, Redetermination of the hyperfine splitting in the ground state of atomic hydrogen, Phys. Rev. 103, 620\u2013631 (1956).[3.19] R. H. Dicke, The effect of collisions upon the Doppler width of spectral lines, Phys. Rev. 122, 1218\u20131223 (1961).[3.20] L. Galatry, Simultaneous effect of Doppler and foreign gas broadening on spectral lines, Phys. Rev. 9, 701\u2013716 (1967).[3.21] S. G. Rautian and I. I. Sobclman, The effect of collisions on the Doppler broadening of spectral lines, Sov. Phys. Usp. 2 and air broadening in the fundamental bands of HF and HCl, J. Mol. Spectrosc. 122, 41\u201355 (1987).[3.22] A. S. Pine and J. P. Looncy, N2 by Fourier transform spectroscopy, J. Mol. Spectrosc. 148, 324\u2013328 (1991).[3.23] Q. Kou and G. Guelachvili, Self-induced pressure shifts in the 9.4- and 10.4-\u03bcm bands of COThe accuracy of the calibration source.The uncertainty in locating the center of the absorption line.The accuracy of transferring the calibration to the line center measurement.Errors caused by environmental effects.Model errors, or uncertainties in the application of least-squares techniques to obtain the best estimate of the correct line frequency.The standards presented in this book are based on data derived in large part from frequency measurements because such measurements are less prone to systematic errors. In assessing the uncertainties that should be assigned to the recommended calibration frequencies, we must consider five major factors that may contribute to error in the determination of the line frequencies.In succeeding paragraphs of this section each of these factors will be examined in relation to the calibration frequencies recommended in this book.v2 band of OCS, . The most important of these were two saturated absorption measurements made by Fayt et al. [5.126] which considerably reduce the uncertainty in the frequencies for 2v2. The measurement of the laser transitions of N2O by Whitford et al. [5.183] gave accurate frequencies for the separation of the v1 and v3 states which were useful for the tables between 880 and 980 cm\u22121. Recently frequency measurements have been made by Urban and coworkers .Much of the primary infrared data used for these tables originated at the NIST laboratory in Boulder, Colorado. Two other laboratories have reported heterodyne frequency measurements on the 22 lasers that were virtually identical to the lasers used by Petersen et al. in the last major determination of the CO2 laser frequencies. Since much of the laser technology that went into the determination of the CO2 laser frequencies was developed in the same laboratory where the heterodyne measurements were made, one can be sure of the accuracy of the calibration source. These lasers have been described in Sec. 2. The CO2 laser frequencies are good to at least \u00b10.05 MHz and are not a significant source of error for the Doppler limited heterodyne measurements.The NIST measurements used well characterized COTwo major factors contribute to errors in the location or determination of absorption line centers: the signal-to-noise ratio, and the slope or other irregularities in the background.For the infrared measurements the slope or irregular background in the radiation being absorbed was only a minor contributor to error since its effect could be practically eliminated, as described in Sec. 2.2O is not as good because all of its transitions have a small quadrupole splitting. Since the splitting for N2O is never greater than 4 MHz and diminishes rapidly with increasing J-values and since the Doppler fullwidth of N2O at 500 cm\u22121 is 28 MHz, the splitting should not affect the use of N2O for most infrared calibration purposes.In some cases imperfectly resolved or overlapping lines were measured. In cases where the lines are close doublets, the measurement represents the center of gravity of the doublets, and the least-squares analysis took that into account. If the lines were partially resolved, that was taken into account in assigning the uncertainty for the measurement. In most cases partially resolved lines that have unequal intensities should not be used unless a very generous allowance is made for the uncertainty since the resulting error is not random, but is in a particular direction. OCS, CO, and CS2 are good molecules to use for standards because they have no quadrupole fine structure. NFor each infrared heterodyne frequency measurement two line centers must be measured: the absorption line center, and the center of the difference frequency . The location of the absorption line center is determined by the technique used to lock the TDL to the absorption line as described in Sec. 2. The uncertainty assigned to the line-center lock is given by half the Doppler-width of the line divided by the signal-to-noise ratio of the derivative signal for the line. Because of modulation broadening the linewidth is slightly greater than the Doppler-width but this approximation to the lock uncertainty is adequate. The lock error is random and is reflected in the statistical analysis of the least-squares fit of many measurements.More important than the uncertainty in locking to the line center is the uncertainty in the difference frequency measurements. That uncertainty is given by one-tenth the beat note linewidth, or by half the beat note width divided by the signal-to-noise ratio, whichever is larger. We believe this covers both random and residual systematic errors for a single measurement. In most of our measurements, this has been the predominant uncertainty and the lock uncertainty has been negligible by comparison.One source of error in the heterodyne measurements that has no direct counterpart in wavelength measurements is due to frequency-dependent differences in the transmission or amplification components involved in the heterodyne frequency measurements. This frequency dependence sometimes presented an additional distortion to the heterodyne frequency lineshape as displayed by the spectrum analyzer. Fortunately this error, which would be systematic for all measurements of the same heterodyne frequency, becomes randomized if enough different lines are measured. In most cases this problem was recognized and was taken into account in estimating the uncertainty of each measurement.Examination of our results over the past decade indicates that the procedure outlined above for assigning the uncertainty produced values which turned out to be close to a 2 \u03c3 uncertainty.For the microwave and sub-millimeter wave measurements used to prepare these tables, the uncertainties given in the literature are generally accurate enough although we have increased the uncertainties slightly in a few cases. There may be some systematic error due to incomplete modulation when Stark modulation was used, but this is compensated by the much smaller linewidths, and the smaller frequency dependent irregularities, compared to the infrared measurements.The primary difference in the reliability of wavelength and frequency measurements is in the accuracy of transferring the calibration to the measurement. In frequency measurements the accuracy of the measurements is not affected by beam dimensions, by wavefront mismatch or other misalignments, or by refractive index effects. The frequency of the radiation is always the same no matter what the medium may be, or how it is measured. Modern electronics excel at counting, and that is how frequency is determined. With frequency measurements, if a measurement can be made at all, the uncertainty must come from the four other sources of error discussed in this chapter.On the other hand, wavelength comparisons are susceptible to many different wavelength-dependent errors, errors due to misalignment, errors due to differences in the ratio of the dimensions of the optical elements , to the wavelength. The best wavelength measurements use a calibration that is nearly the same wavelength and intensity as the feature to be calibrated. Each type of wavelength measurement has its own peculiarities.\u22121 band-pass of the FTS measurements. For the FTS measurements there may be a phase error which is different for weak features and for strong features and that is one reason why greater emphasis was placed on the use of frequency measurements of pure rotational transitions to determine the rotational constants wherever possible. In no case were FTS measurements used to determine the band centers or vibrational levels for the lines recommended as frequency standards.The present tables are based in part on higher order centrifugal distortion constants determined to some extent by FTS measurements which are essentially wavelength measurements. These measurements were all internally calibrated by means of lines whose frequency could be determined by heterodyne frequency measurements. These calibration features were always within the approximately 120 cmFor closed shell molecules the only significant environmental effects are due to pressure shifts and electric field effects such as either the ac or dc Stark effects. As long as the radiation field (for absorption spectra) is too low to give saturated absorption effects, the ac Stark effect can be ignored in its effect on the absorption line center. Even the dc Stark effect can be ignored for most work since stray electric fields are generally too small to give noticeable Stark shifts.We believe that even in the case of the saturated absorption measurements on the 2-0 band of CO, the shift due to the ac Stark effect will be smaller than a tenth of the linewidth, or less than 0.2 MHz.2 lasers but, since those lasers have the same characteristics as the lasers used in the original measurements against the cesium frequency standard, the effect of the shift will already be included in the frequency assigned to the laser lines. In the case of the CO transfer oscillators, the CO frequencies are measured at the same time as the beat note frequency measurement and any ac shift is included in the measurement.The ac Stark effect may have a small effect on the frequency of the COv2 band of OCS. Since neither the frequency dependence nor the rotational or vibrational dependence of the pressure shift is known, this remains one of the most important uncertainties in the application of these tables to real measurements.On the other hand, the effect of pressure induced shifts is potentially significant and deserves serious consideration. Pressure-induced shifts in infrared spectra have not been extensively studied, so there is no experimentally confirmed theory that one can use to calculate the pressure shifts to be expected for much of the data given in the present tables. All of the pressure shift measurements seem to indicate that the shift for the transitions given in these tables may be on the order of \u22122.2kHz/Pa (\u22120.3 MHz/Torr) or less. Only in the case of the measurements given by Vanek et al. [9.133] is the shift of \u22120.37 \u00b10.04 kHz/Pa (\u221249 \u00b15 kHz/Torr) reliably given for the 2l-type resonance was included because it represents the largest resonance effect and it can be reliably estimated, thereby giving the correct functional form to the centrifugal distortion constants. The details of the fitting procedure and Hamiltonian are given in Sec. 3.Because individual measurements of infrared absorption lines by heterodyne measurement techniques are not very precise (uncertainties of the order of 5 to 10 MHz for some regions) and only a small number of transitions can be measured, it is necessary to use least-squares techniques to combine all available measurements to yield calculated transitions that are considerably more accurate than any one measurement. Such fitting techniques can be no more accurate than the equations used to describe the transitions (the Hamiltonian). The molecules and the particular transitions in these tables were chosen in part because of the reliability of the Hamiltonian as shown by extensive studies reported in the literature. Although certain interactions, such as Fermi resonance, affect the constants used in the effective Hamiltonian, such resonances can be ignored, provided that measurements are available for a wide range of rotational levels for each vibrational state. In the analysis used in this book the effect of J-value for which there are good measurements. Higher transitions are given in the tables but their accuracy is less certain.The variance-covariance matrix determined by the least-squares fit gives a reliable estimate of the uncertainties of the transitions in the range of rotational levels for which there are good measurements. The calculated uncertainties get large quite rapidly for transitions extrapolated beyond the range of measured energy levels, but the reliability of those calculated uncertainties deteriorates even more quickly. For that reason we have terminated the recommended calibration standard indication at the highest Of the five sources of error identified above, the first does not contribute significantly to the uncertainties in the calibration frequencies given in these tables. For frequency measurements the second and third source will appear as random errors and so will be given by the statistical analysis of the least-squares fit of the measurements. For the molecules and bands represented in these tables the uncertainties contributed by model errors are small and likely to show as deviations that are included in the statistical analysis.In conclusion we think that the uncertainties given by the statistical analysis are adequate to describe the errors in the frequency measurements that might arise from all causes except errors due to pressure-induced frequency shifts. Most of the heterodyne measurements were made at low pressures but some measurements of weaker transitions were made at pressures as great as 1200 Pa (9 Torr). To allow an extra margin of error due to pressure shifts, the uncertainties assigned to the heterodyne frequency measurement data used in the fit were about twice as large as the rms deviation. Primarily, this had the effect of increasing the uncertainty in the vibrational energy levels.F \u2014 frequency measurements,FB \u2014 foreign gas broadening measurements,I \u2014 intensity measurements,LS \u2014 laser-Stark measurements,PS \u2014 pressure shift measurements,SB \u2014 self-broadening measurements,T \u2014 theory, andW \u2014wavenumber or wavelength measurements.We attempt here to list all references to papers giving infrared or microwave frequency (or wave-number) measurements, as well as lineshape and intensity measurements that are relevant to this atlas. Papers involving bands not included in this atlas may be missing from this bibliography. Some papers are not included if they involve foreign gas broadening measurements only. For a more complete listing of pressure broadening papers see the review given by Smith et al. [5.2]. When completely superseded, some of the older papers may not appear in this bibliography but they can be found referenced in the more recent papers. The references are grouped by molecule and arranged in chronological order for each molecule. At the end of each reference is a list of initials that indicate the subject matter covered by the reference as follows:[5.1] L. A. Pugh and K. Narahari Rao, in Molecular Spectroscopy: Modern Research, Vol. II , pp. 165\u2013227 Academic Press, New York (1976) I.[5.2] M. A. H. Smith, C. P. Rinsland, B. Fridovich, and K. Narahari Rao, in Molecular Spectroscopy: Modern Research, Vol. III , pp. 111\u2013248. Academic Press, San Diego (1985) I.FB.SB.3, 221\u2013244 (1974) F.[5.3] A. G. Maki, Microwave spectra of molecules of astrophysical interest VI. Carbonyl sulfide and hydrogen cyanide, J. Phys. Chem. Ref. Data 3, 609\u2013770 (1974) F.[5.4] F. J. Lovas, Microwave spectral tables. I. Diatomic molecules, J. Phys. Chem. Ref. Data 7, 1445\u20131750 (1978) F.[5.5] F. J. Lovas, Microwave spectral tables. II. Triatomic molecules, J. Phys. Chem. Ref. Data 14S and the nuclear spin of C14, Phys. Rev. 73, 1405 (1948) F.[5.6] A. Roberts, Rotational spectrum of OC74, 1113\u20131133 (1948) F.[5.7] C. H. Townes, A. N. Holden, and F. R. Merritt, Microwave spectra of some linear XYZ molecules, Phys. Rev. 75, 270\u2013278 (1949) F.[5.8] M. W. P. Strandberg, T. Wentink, and R. L. Kyhl, Rotational absorption spectrum of OCS, Phys. Rev. 17 and S36 in the rotational spectrum of OCS, Phys. Rev. 75, 529\u2013530 (1949) F.[5.9] W. Low and C. H. Townes, O35 from microwave spectroscopy, Phys. Rev. 81, 948\u2013951 (1951) F.[5.10] T. Wentink, W. S. Koski, and V. W. Cohen, The Mass of S84, 1178\u20131180 (1951) F.[5.11] C. M. Johnson, R. Trambarulo, and W. Gordy, Microwave spectroscopy in the region from two to three millimeters, part II, Phys. Rev. 2, J. Chem. Phys. 19, 881\u2013886 (1951) I.[5.12] D. Z. Robinson, The experimental determination of the intensities of infrared absorption bands. IV. Measurements of the stretching vibrations of OCS and CSA208, 341\u2013351 (1951) I.[5.13] H. J. Callomon, D. C. McKean, and H. W. Thompson, Intensities of vibration bands. IV. Carbonyl sulphide and acetylene, Proc. Roy. Soc. (London) 20, 520 (1951) I.[5.14] D. C. McKean, H. J. Callomon, and H. W. Thompson, Intensities of vibration bands of carbonyl sulfide and carbon disulfide, J. Chem. Phys. 17, Phys. Rev. 85, 474\u2013477 (1952) F.[5.15] S. Geschwind, G. R. Gunther-Mohr, and G. Silvey, The spin and quadrupole moment of O33 from microwave spectroscopy, Phys. Rev. 85, 532\u2013539 (1952) F.[5.16] J. R. Eshbach, R. E. Hillger, and M. W. P. Strandberg, The nuclear magnetic moment of S2O, Phys. Rev. 88, 772\u2013774 (1952) F.[5.17] S. J. Tetenbaum, Six-millimeter spectra of OCS and N35 by microwave spectroscopy, Phys. Rev. 93, 193\u2013194 (1954) F.[5.18] B. F. Burke, M. W. P. Strandberg, V. W. Cohen, and W. S. Koski, The nuclear magnetic moment of S3F, and H2O, Phys. Rev. 93, 407\u2013412 (1954) F.[5.19] W. C. King and W. Gordy, One-to-two millimeter wave spectroscopy. IV. Experimental methods and results for OCS, CH93, 897\u2013898 (1954) F.[5.20] C. A. Burrus and W. Gordy, Submillimeter wave spectroscopy, Phys. Rev. 22, 1949\u20131950 (1954) I.[5.21] E. C. Wingfield and J. W. Straley, Intensity of the bending mode in carbonyl sulfide, J. Chem. Phys. 97, 1664\u20131667 (1955) F.[5.22] W. Low, Fermi resonance in the microwave spectrum of linear XYZ molecules, Phys. Rev. 26, 400\u2013403 (1957) W.[5.23] H. C. Allen, E. K. Plyler, and L. R. Blaine, Infrared spectrum of carbonyl sulfide, J. Chem. Phys. 66A, 163\u2013167 (1962) W.[5.24] A. G Maki, E. K. Plyler, and E. D. Tidwell, Vibration-rotation bands of carbonyl sulfide, J. Res. Natl. Bur. Stand. (U.S.) 16O13C32S entre 3650 cm\u22121 et 7000 cm\u22121, Ann. Soc. Scient. Bruxelles 79, 193\u2013221 (1965) W.[5.25] E. A. Triaille, Spectres de vibration-rotation a haute resolution du 18, 118\u2013128 (1965) W.[5.26] E. A. Triaille and C. P. Courtoy, Further evidence for perturbations in the infrared spectra of carbonyl sulfide, J. Mol. Spectrosc. 8, 334\u2013335 (1966) W.[5.27] T. F. Deutsch, OCS molecular laser, Appl. Phys. Lett. 45, 1861\u20131865 (1966) I.[5.28] H. Yamada and W. B. Person, Absolute infrared intensities of some linear triatomic molecules in the gas phase, J. Chem. Phys. 40, 1095\u20131100 (1967) F.[5.29] Y. Morino and C. Matsumura, Microwave spectra and equilibrium structure of carbonyl sulfide, Bull. Chem. Soc. Japan 18, 105\u2013107 (1967) F.[5.30] R. 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An interpretation of the bond moments of CO2 and CS2, Spectrochimica Acta 20, 771\u2013779 (1964) I.[5.379] W. B. Person and L. C. Hall, Absolute infrared intensities of CS45, 1861\u20131865 (1966) I.[5.380] H. Yamada and W. B. Person, Absolute infrared intensities of some linear triatomic molecules in the gas phase, J. Chem. Phys. 12CS2 and 13CS2 and the v3 \u2013 v1, v3\u2013 2v2 and v3 + 4v2 bands, Spectrochim. Acta A 27, 1979\u20131987 (1970) W.[5.381] D. F. Smith, T. Chao, J. Lin, and J. Ovcrcnd, High resolution of 2 in the region of the bending fundamental v2, J. Mol. Spectrosc. 82, 214\u2013219 (1980) W.[5.382] K. Jolma and J. Kauppinen, High-resolution infrared spectrum of CSv3 du disulfure de carbone 12C34S2 et 13C34S2, Ann. Soc. Scient. Bruxelles 94, 129\u2013139 (1980) W.[5.383] G. Blanquet, J. Walrand, and C. P. Courtoy, La bande 12C32S2 et 12C34S2 la bande v3 \u2013 v1, Ann. Soc. Scient. Bruxelles 97, 229\u2013241 (1984) W.[5.384] E. Baeten, G. Blanquet, J. Walrand, and C. P. Courtoy, Spectres infrarouges a haute resolution du disulfure de carbone v3 \u2013 v1 region of CS2, Can. J. Phys. 62, 1286\u20131292 (1984) W.[5.385] E. Baeten, G. Blanquet, J. Walrand, and C. P. Courtoy, Tunable diode laser spectra of the v3 band region of four isotopic forms of CS2, J. Mol. Spectrosc. 110, 65\u201373 (1985) W.[5.386] J. Lindenmayer and H. Jones, Diode laser spectroscopy of the 112, 55\u201370 (1985) W.[5.387] G. Blanquet, E. Baeten, I. Cauuct, J. Walrand, and C. P. Courtoy, Diode-laser Measurements of carbon disulfide and general rovibrational analysis, J. Mol. Spectrosc. v3 \u2013 v1 band of CS2, Mol. Phys. 58, 995\u20131000 (1986) I.[5.388] M. Dang-Nhu, G. Blanquet, J. Walrand, and C. P. Courtoy, Spectral intensities in the 2 in the v3 band region, Z. Naturforsch. 43a, 215\u2013218 (1988) W.[5.389] F. Winther, U. Heyne, and A. Guarnieri, The infrared spectrum of CS\u22121 region from heterodyne frequency measurements on the v3 bands of 12CS2 and 13CS2, J. Mol. Spectrosc. 132, 422\u2013428 (1988) F.[5.390] J. S. Wells, M. Schneider, and A. G. Maki, Calibration tables covering the 1460-1550-cm\u22121 and 4071 to 4352 cm\u22121CO Atlas\u20131948 to 2275 cm\u22121OCS Atlas\u2013486 to 567 cm\u22121OCS Atlas\u2013812 to 890 cm\u22121OCS Atlas\u20131000 to 1095 cm\u22121OCS Atlas\u20131650 to 1739 cm\u22121OCS Atlas\u20131832 to 1934 cm\u22121OCS Atlas\u20131970 to 2141 cm\u22121OCS Atlas\u20132510 to 2600 cm\u22121OCS Atlas\u22122693 to 2763 cm\u22121OCS Atlas\u20132862 to 2970 cm\u22121OCS Atlas\u20133065 to 3120 cm2O Atlas\u2013523 to 659 cm\u22121N2O Atlas\u2013880 to 1087 cm\u22121N2O Atlas\u20131105 to 1345 cm\u22121N2O Atlas\u20131820 to 1925 cm\u22121N2O Atlas\u20132140 to 2269 cm\u22121N2O Atlas\u20132400 to 2607 cm\u22121N2O Atlas\u20132725 to 2842 cm\u22121N2 Atlas\u20131460 to 1551 cm\u22121CS\u22121NO Atlas\u20131741 to 1940 cmThe range of wavenumber coverage of the molecular bands is indicated below for the five molecules selected for use.Throughout the wavenumber tables the lines that are suitable for use as wavenumber standards are indicated by an asterisk (*) following the wavenumber and its uncertainty. In assigning the asterisks no consideration was given to problems related to overlapping with other transitions. The tables list nearby lines that may cause problems with overlapping. The user must exercise judgment in determining if such overlapping will impair the accuracy of the measurement. The asterisk only certifies the accuracy of the line position in the hypothetical absence of any other nearby lines. Obviously, the resolution of the instrumentation being used will determine if a nearby line might invalidate the accuracy of a calibration line.The uncertainties of the wavenumbers are given in parentheses after the wavenumbers in those cases where there is reason to believe that a good estimate of the uncertainty can be made. Even so, the uncertainty in the lines not designated as calibration lines should be taken with some degree of skepticism.The uncertainties given in the tables are twice the estimated standard error as calculated from the variance-covariance matrix given by the least-squares fit that determined the constants used to calculate the wavenumbers. The uncertainties refer to the accuracy of each individual transition. In general, the wavenumber separation of two nearby lines for the same vibrational transition of the same molecular species will be given more accurately than the uncertainty given in parentheses might lead one to believe. That is because the relative differences between the rotational energy levels are usually known more accurately than the differences in the vibrational energy levels.On the other hand, the separation of two lines that are due to absorption from two different isotopic species is probably known no more accurately than the uncertainty (given in parentheses) would lead us to believe.The wavenumbers given in the tables are calculated wavenumbers because they are more reliable than individual line measurements and the uncertainties in the calculated wavenumbers can be accurately estimated.S in The wavenumber tables also contain a column for the intensity estimated for each transition at a temperature of 296 K. The format for the intensity values is the standard computer format consisting of a decimal value followed by the exponent . The intensities given in the wavenumber tables are represented by 2O also contain a column giving the separation (in cm\u22121) of the lower state energy level from the ground state. The units given in the tables can be converted to the more common units of cm\u22122 atm\u22121 at 296 K by multiplying by 2.479 \u00d7 1019. To convert to intensities at some other temperature one should refer to In the sections giving discussions and equations on intensity calculations and on pressure broadening (Sec. 3), equations are given for estimating the appearance of the spectrum for different experimental conditions. In particular, The intensity values given in this work are only given as an aid in estimating the appearance of the spectrum, they should not be treated as well determined values. The intensities given for weak lines and especially for the rarer isotopes may be in error by 50 percent or more.\u22121. Close doublets that should have the same intensity may show slight intensity differences because of this digitizing effect.The spectral illustrations were actually calculated spectra rather than reproductions of real measurements. This gave us more flexibility in choosing effective pressures and pathlengths that seemed most appropriate to illustrate even the weak lines. As with any digitized spectrum, regardless of whether it is calculated or measured, the peak intensity of sharp lines may show some irregularity depending on whether the true peak falls on a digitized point or slightly misses it. The spectra were plotted with a digitizing interval of about 0.0005 to 0.001 cm2O or CO2 will not be found in these spectra.Comparison with real spectra measured in our own laboratory or illustrated in published works showed that the spectra given in this work are adequate for identifying the calibration lines. Some weak transitions may be absent from the calculated spectrum even though they might be found in a real spectrum of comparable pressure and pathlength. Certainly, absorption due to common impurities such as H\u22121 (FWHH) at 2000 cm\u22121 and 0.0093 cm\u22121 at 4000 cm\u22121. For the conditions chosen for the atlas illustrations, the strong CO lines are much broader than the weak ones and show pronounced shoulders due to the effect of even a very small pressure broadening.The spectra used in the illustrations for CO were calculated for infinite resolution but the lines were given widths dictated by the Doppler width of the line convolved with the pressure broadened width. For the CO spectra the shape of the weak lines is dominated by the Doppler width which is 0.0047 cm2O spectra were calculated for spectrometer resolutions on the order of 0.003 cm\u22121. Again the expected Doppler and pressure-broadened lineshapes were used in calculating the spectra. The atlas for OCS and N2O is divided into sections according to the vibrational transitions involved. At the beginning of each section the parameters used in calculating the spectra are given as well as a key to the abbreviations used for the vibrational transitions in the atlas.The figures used for illustrating the OCS and NIn calculating the pressure-broadened width, a single value for the pressure broadening was used for all lines in a spectrum. It is well known that such an assumption is incorrect and therein lies one reason for the illustration to depart slightly from a true spectrum.The spectra overlap slightly in order to show the relationship of the lines near the ends of each panel. At the top of each spectrum fiducial marks indicate which lines are given in the accompanying wavenumber tables. Every fifth line is indicated with a darker and longer mark. In the tables, every fifth line is set apart by a following blank line. Even though the panels overlap, each line is identified by a fiducial mark only once. The next section gives a key to symbols in the atlas, followed by a sample spectral map with facing table.e or f designation is not specified (for l \u2260 0), then the transition is to either level, depending on the selection rules and the change in the rotational quantum number, J. Spectra are given for a slitwidth of 0.002 cm\u22121 and a temperature of 296 K. For the A, X, D, P, and T bands a transition moment of 0.0333 D was used and no Herman-Wallis constant was included in the intensity calculation. For the other bands a transition moment of 0.032 D was used with a Herman-Wallis constant of C1 = 0.0019.If the"} +{"text": "Scientific Reports6: Article number: 2549110.1038/srep25491; published online: 05062016; updated: 08262016The original version of this Article contained an error in the spelling of Dan Jia which was incorrectly given as Jia Dan. As a result, the Author Contribution statement now reads:\"X.F.C., Y.D. and L.Z. conceived and designed the experiments; X.X.W., D.J., Y.C., Z.Y.G. and S.H.G. performed the experiments; X.X.W., X.F.C. analyzed the data; X.X.W., X.F.C. wrote the manuscript; Y.F.C., P.Z. and Y.D. reviewed the manuscript.\"In Figure 5c, the labels for the CDK1 panels were inverted, where \u2018siSrc\u2019 and \u2018siNC\u2019 were incorrectly given as \u2018siNC\u2019 and \u2018siSrc\u2019 respectively. The correct Figure 5 appears below as These errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition. Glaucoma is the most common cause of irreversible blindness worldwide. Here, the authors carry out a large meta-analysis of genetic data from individuals of European and Asian ancestry and identify 10 new loci associated with vertical cup-disc ratio, a key factor in the clinical assessment of patients with glaucoma. The aim of the study is to identify loci associated with VCDR, and to determine whether these variants are also associated with glaucoma.We perform the meta-analysis in four stages. In the first stage, we meta-analyse summary data from 10 populations of European ancestry comprising 21,094 individuals. In the second stage, we test the cross-ancestry transferability of the statistically genome-wide-significant associations from the first stage in 6,784 individuals from four Asian cohorts. In the third stage, we examine whether the associations are independent of disc area and/or spherical equivalent. We also combine the genome-wide-significant effects into a genetic risk score and associate this score with the POAG risk in five populations. Finally, we perform gene-based tests and pathway analysis.We find 10 new loci associated with VCDR, which together increase the risk on POAG 2.5 times. Our findings will help us to unravel the pathogenesis of glaucoma.\u03bb) varied between 0.98 and 1.12, implying adequate within-study control of population substructure located across 15 chromosomal regions (P<0.05) with an effect in the same direction and generally the same order of magnitude \u2014either directly genotyped or imputed in 21,094 subjects of European ancestry . The inftructure . The ove regions . In stagagnitude . Five ofagnitude ; Fig. 1. CARD10) . There w CARD10) . The eff CARD10) .CDC7/TGFBR3, ATOH7, SALL1 and CARD10)10P=3.48 \u00d7 10\u221211 to P=9.00 \u00d7 10\u22123) at the CDC7\u2013TGFBR3 locus, suggesting the VCDR association at this locus is explained primarily by its known association with disc area . There was no change in association significance for any of the 10 new loci reported here, suggesting they do not act primarily on disc area.Four of the 18 genome-wide-significant loci have been previously associated with optic disc area (isc area . A similSIX6 and BMP2) overlap with those implicated in myopiaMIR612-SSSCA1 region) was not consistent with the European populations associations with POAG for six newly identified genetic variants , of which 1.6\u20131.8% is explained by the new loci. The phenotypic variability explained by all common SNPs is 41\u201353% in these cohorts, which is in line with the heritability estimates from family-based studies. In addition to confirming the previously published 6 tests) , with od6 tests) for thosPgene-based<0.05/17,872=2.80 \u00d7 10\u22126. In addition to the SNPs identified as significant (P<5 \u00d7 10\u22128) in a SNP-based test, we also found two new genes significantly associated with VCDR using the VEGAS gene-based test (REEP5 (P=7.48 \u00d7 10\u22127) and PITPNB (P=4.89 \u00d7 10\u22127). PITPNB is ~800\u2009kb from another gene with a significant SNP association ) to the CHEK2 peak. The results we obtained using the specified definition of the gene unit were substantially the same when alternative cutoff points from the transcription initiation and end sites were used (P=0.03) in the gene-based test, with a best single SNP P value of 0.003, but this was not confirmed in two other studies.To identify new loci not previously found through individual SNP-based tests, we performed gene-based tests using VEGAS softwaresed test . These w1547014) . Althougere used . The REEith POAG . The PIT\u22125 . The only pathway exceeding the pathway-wide significance level was \u2018negative regulation of cyclin-dependent protein kinase activity\u2019 also contributes to the pathway result. The APC gene has previously been reported to be a critical gene regulating retinal pigment epithelium proliferation and developmentBMP2 (bone morphogenetic protein 2) gene on chromosome 20 belongs to the TGFB super-family. Two other new genes regulate apoptosis: RPAP3 (RNA polymerase II-associated protein 3) on chromosome 12CARD10, a gene that was previously found to be associated with disc areaSALL1This study reports 10 novel loci associated with VCDR, with an additional two loci identified using gene-based testing. Pathway analysis suggests retardation of cell growth as a major biological mechanism. The results for the most associated pathways \u2018negative regulation of cyclin-dependent protein kinase activity\u2019 and \u2018negative regulation of epithelial cell proliferation\u2019 are primarily driven by the COL8A1 is part of a collagen pathway recently implicated in corneal thicknessCOL8A2 were found in POAG patients with a very thin central corneal thickness (CCT)\u03b2=\u22120.044, P=0.19; in Asians: \u03b2=0.007, P=0.89) or intraocular pressure in largely the same cohorts18DUSP1 is the nearest gene to the most strongly associated SNP on chromosome 5. This gene, inducible by oxidative stress and heat shock, may play a role in environmental stress responseHSF2 (heat shock transcription factor 2), one of the genes at the chromosome 6 locus, also is part of the cellular stress response pathway. Deficiency of this factor causes various central nervous system defects in mice24EXOC2 (exocyst complex component 2). The encoded protein is one of the eight proteins of the exocyst complexPLCE1 , belongs to the phospholipase C family, which plays a role in the generation of second messengersADAMTS8 are of interest. ADAMTS enzymes have different functions, including the formation and turnover of the extracellular matrixADAMTS10 has been linked to a form of glaucoma in dogs30Our findings offer new insights in the aetiology of optic nerve degeneration. In summary, we have now identified 10 novel loci associated with cupping of the optic nerve, a key determinant of glaucoma. Together, these genetic risk variants increased the risk of POAG in case-control validation studies. Pathway analysis implicated negative regulation of cell growth and cellular response to environmental stress as key pathological pathways in glaucoma, and that novel therapies targeting these pathways may be neuro-protective in glaucoma.We performed a meta-analysis on directly genotyped and imputed SNPs from individuals of European ancestry in 10 studies, with a total of 21,094 individuals. Subsequently, we evaluated significantly associated SNPs in 6,784 subjects of Asian origin including four different studies and performed a meta-analysis on all studies combined.All studies included in this meta-analysis are part of the International Glaucoma Genetics Consortium. The ophthalmological examination of each study included an assessment of the optic nerve head to measure the VCDR . UnreliaThe meta-analysis of stage 1 was based on 10 studies of European ancestry: Brisbane Adolescent Twin Study, Blue Mountains Eye Study, Erasmus Rucphen Family Study, Gutenberg Health Study (GHS I/GHS II), Glaucoma Genes and Environment (controls only), National Eye Institute Glaucoma Human Genetics Collaboration , Raine Study, Rotterdam Study (RS-I/RS-II/RS-III), Twins Eye Study in Tasmania and TwinsUK. Stage 2 comprised four Asian studies: Beijing Eye Study, Singapore Chinese Eye Study, Singapore Malay Eye Study and Singapore Indian Eye Study. For each SNP with the strongest association at each locus the association with POAG was tested in five case-control studies: ANZRAG, deCODE, Massachusetts Eye and Ear Infirmary, NEIGHBOR and Southampton.Information on general methods, demographics, phenotyping and genotyping methods of the study cohorts can be found in Information on genotyping in each cohort and the particular platforms used to perform genotyping can be found in more detail in Each study applied stringent quality control procedures before imputation, including minor allele frequency cutoffs, Hardy\u2013Weinberg equilibrium, genotypic success rate, mendelian inconsistencies, exclusion of individuals with >5% shared ancestry (exception made for family-based cohorts in which due adjustment for family relationship was made) and removal of all individuals whose ancestry as determined through genetic analysis did not match the prevailing ancestry group of the corresponding cohort . SNPs wiIn subjects drawn from their respective populations in which the prevalence of glaucomatous changes is relatively low, the correlation between left and right eye is high35P values for the association results were calculated by using the z-statistic. P values for heterogeneity were calculated by using the Cochran\u2019s Q-test for heterogeneity. In addition to this, I2 values were calculated to assess heterogeneityFst values were calculated to assess the genetic variation due to subdivision of populations. All study effect estimates were corrected using genomic control and were oriented to the positive strand of the NCBI Build 36 reference sequence of the human genome, which was the genomic build on which most available genotyping platforms were based. Coordinates and further annotations for the SNPs were converted into Build 37, the most recent version of the available builds at the time of this study.We performed an inverse variance weighted fixed-effect meta-analysis. This was performed with METAL softwareP value <5.0 \u00d7 10\u22128 (the genome-wide threshold of association) was considered significant. In stage 2, a P value <0.05 was considered significant. Manhattan, regional and forest plots were made using RIn stage 1, a In five case-control studies, a weighted genetic risk score per individual was calculated. Standardized regression coefficients were used as weighting factor. The weighted risk scores were divided into quintiles. Odds ratios were calculated for each quintile, using the first quintile as a reference.P values. VEGAS was applied to the summary data from the full VCDR analysis of randomly drawn \u03c72-test statistics was summed. To ensure clusters of genes did not adversely affect results, within each pathway, gene sets were pruned such that each gene was >500\u2009kb from all other genes in the pathway. Where required, all but one of the clustered genes was dropped at random when genes were clustered. Pathway-VEGAS was performed separately for European and Asian ancestry data sets. Meta-analysis was conducted using Fisher\u2019s method for combining P values.Pre-specified pathways from the Gene Ontology database with size ranging in 5\u2013500 genes were used to perform pathway analysis. Pathway-VEGAS combines VEGAS gene-based test statistics based on pre-specified biological pathwaysWe used the ENCyclopedia Of DNA ElementsWe examined the expression of genes that reached significance in the individual SNP-based test or gene-based test. We used published literature or human ocular gene expression databases .H.S., R.H., A.Mishra, P.G.H., C.-C.K. and S.J.L. contributed equally to this work. N.P., T.-Y.W., L.R.P., A.W.H., C.M.v.D. and C.J.H. jointly supervised this work. H.S., R.H., P.G.H., T.-Y.W., L.R.P., A.W.H., C.M.v.D. and C.J.H. performed analyses and drafted the manuscript. J.B.J., A.C.V., C.C.W.K., J.E.C., S.M., D.A.M., A.J.L., J.L.W., N.P., T.-Y.W., L.R.P., A.W.H., C.M.v.D. and C.J.H. jointly conceived the project and supervised the work. W.D.R., E.V., M.E.N., G.W.M., L.X., J.E.M., Y.L., N.A., L.C.K., K.-S.S., E.M.v.L., A.I.I., V.J.M.V., M.A.H., S.-C.L., D.D.G.D., A.N., C.V., P.G.S., A.S., J.H.K., J.L., F.J., A.J.C., L.M.E.v.K., F.R., E.S., V.J., G.M., R.N.W., P.T.V.M.d.J., B.A.O., A.G.U., A.H., S.E., T.D.S., A.Mirshahi, S.-M.S., J.R.V., Y.-Y.T., R.C.W.W., H.G.L., E.-S.T., N.M.J., C.-Y.C., T.A., Blue Mountains Eye Study-GWAS Group, NEIGHBORHOOD Consortium, and Wellcome Trust Case Control Consortium 2 (WTCCC 2) were responsible for study-specific data. H.S., S.J.L., J.N.C.B., J.G., G.T., P.G., U.T., K.P.B., J.L.H., J.E.C., A.J.L., K.S. and J.L.W. were involved in the genetic risk-score analysis. S.F.J., X.L., A.A.B.B. and T.L.Y. performed the data expression experiments. A.Mishra and S.M. were involved in pathway analyses. A.Mishra, C.-C.K., W.D.R., P.T.V.M.d.J., H.G.L., N.M.J., J.B.J., A.C.V., C.C.W.K., J.E.C., S.M., D.A.M., A.J.L. and J.L.W. critically reviewed the manuscript.How to cite this article: Springelkamp, H. et al. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat. Commun. 5:4883 doi: 10.1038/ncomms5883 (2014).Supplementary Figures 1-7, Supplementary Tables 1-17, Supplementary Note, Supplementary Methods and Supplementary References"} +{"text": "Borrelia burgdorferi sensu lato species in Europe shows very dynamic spatial and temporal variations. Since different Borrelia species usually correlate with different clinical manifestation of Lyme borreliosis, knowledge of the geographic distribution of the pathogen is very important for understanding the ecology and epidemiology of the disease. Our previous studies, based on direct molecular methods, revealed high diversity of species of the B. burgdorferi s.l. complex and unexpected high prevalence of B. lusitaniae in Ixodes ricinus ticks from Serbia. The aim of the present study was further isolation and typization of viable B. burgdorferi s.l. strains from vectors in Serbia as a basis for studies of biological, genetic and ecological variations.The geographic distribution of I. ricinus ticks collected from 24 localities were processed for cultivation. Prior to cultivation, all ticks were disinfected, then triturated in BSK H medium. The culture tubes were incubated at 33\u00b0C for 3 months. Cultures were periodically examined by dark field microscopy. For confirmation of isolated strains, \"seminested\" PCR for the flaB gene was performed. Determination of B. burgdorferi s.l. species was carried out by the RFLP technique, using restriction enzymes MseI and DraI on the previously amplified 5-23S rDNA intergenic spacer . For Borrelia identification by RT-PCR targeting, the hbb gene protocol of Portno\u00ef et al. (2006) was followed. Sequencing of the 5-23S rDNA intergenic spacer and flaB gene was performed for phylogenetic analysis.A total of 248 adult B. lusitaniae, B. afzelii, B. burgdorferi s.s., B. garinii and B. valaisiana. For all strains identified as B. lusitaniae, B. garinii, B. afzelii and B. valaisiana according to the MseI-RFLP method, results of RT-PCR were in absolute agreement. However, Tm values for all strains identified as B. burgdorferi s.s. according to RFLP patterns were in the range for B. lusitaniae strains (64.17 to 64.58 \u00b0C). Thus, it was impossible to distinguish B. burgdorferi s.s. and B. lusitaniae strains by this method. Sequencing analysis for strains identified as B. lusitaniae, B. garinii, B. afzelii and B. valaisiana was in agreement with MseI-RFLP and RT-PCR results. In cases of uncoordinated MseI-RFLP and RT-PCR results, sequencing analysis confirmed unclear strains as B. lusitaniae. The results of this study showed B. lusitaniae to be the species with highest prevalence in I. ricinus ticks from Serbia.Thirty-four spirochete cultures were isolated and subjected to further genotyping analyses. According to the RFLP patterns of the 5S-23S rDNA intergenic spacer, specimens were determined as:"} +{"text": "Scientific Reports5: Article number: 1813710.1038/srep18137; published online: 12172015; updated: 02052016This Article contains errors in the Author Contributions Statement.in vivo experiments; R.F. provided clinical samples; F.B. designed in vivo research and edited the manuscript; S.A. conceived of the research, provided clinical samples and edited the manuscript; A.T. conceived the research and edited the manuscript. All authors reviewed and approved the manuscript.\u201d\u201cM.A. designed and performed the research, analyzed data and wrote the manuscript; M.R.R. designed the research, analyzed data and edited the manuscript; S.M. performed metabolic experiments R.L. performed functional assays; S.O., F.R. and G.T. performed should read:in vivo experiments; R.F. provided clinical samples; F.B. designed in vivo research and edited the manuscript; S.A. conceived the research, provided clinical samples and edited the manuscript; M.R.T. edited the manuscript; A.T. conceived the research and edited the manuscript. All authors reviewed and approved the manuscript.\u201d\u201cM.A. designed and performed the research, analyzed data and wrote the manuscript; M.R.R. designed the research, analyzed the data and edited the manuscript; R.L. performed functional assay; S.M. performed metabolic experiments; S.O., F.R. and G.T. performed"} +{"text": "In 2011, the overall age-adjusted death rate for the United States was 741.3 per 100,000 population. Among states, Mississippi had the highest death rate (956.1), followed by West Virginia (953.2), Alabama (933.6), and Oklahoma (910.9). Hawaii had the lowest death rate (584.9), followed by California (641.3), Minnesota (659.2), and Connecticut (660.6). The rates for 27 states and the District of Columbia were higher than the overall U.S. rate.Source: National Vital Statistics System. Mortality public use data files, 2011. Available at http://www.cdc.gov/nchs/data_access/vitalstatsonline.htm.Reported by: Jiaquan Xu, MD, jax4@cdc.gov, 301-458-4086."} +{"text": "In \u201cNeurodevelopmental Disorders and Prenatal Residential Proximity toAgricultural Pesticides: The CHARGE Study\u201d by Shelton et al. , the following disclaimerwas inadvertently omitted from the Competing Financial Interest Declaration:D.J.T., R.J.S., R.L.H., and I.H.-P. have received travel reimbursements and grant supportfrom Autism Speaks, an autism advocacy group. Further, the authors state that theirfreedom to design, conduct, interpret, and publish research is not compromised by anycontrolling sponsor as a condition of review and publication.The authors regret the error."} +{"text": "There is an error in the citation for Dr. Alejandro P. Ugalde. His name should be written Ugalde AP. Please view the correct citation below. The publisher apologizes for the error.10.1371/journal.pgen.1005879Hoffman Y, Bublik DR, Ugalde AP, Elkon R, Biniashvili T, Agami R, et al. (2016) 3\u2019UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells. PLoS Genet 12(2): e1005879. doi:"} +{"text": "Scientific Reports6: Article number: 23034; 10.1038/srep23034 published online: 03142016; updated: 05202016.The Acknowledgements section and Author Contributions statement were omitted from this Article.The Acknowledgements section should read:\u201cFloxed PTEN mice and LysMCre recombinase transgenic mice were kind gifts from T.W. Mak and R. Johnson , respectively. We want to thank Sophie Walter, Susanne Humpeler and Angela Kn\u00f6bl for their great technical assistance and Michael Grusch and Elisabeth Lang for kindly providing us pSMAD2/3 and SMAD2/3 antibodies.Financial support was provided by the Austrian Science Found (FWF) with the projects P24802 to GS and P24973 to AA and GS.\u201dThe Author Contributions statement should read:\u201cJ.B.K. , M.K., W.C.S. , B.B. , J.W. (helped in designing the study and performed experiments), C.W., H.P., M.S., E.S. and J.S.B. , C.\u00d6. (helped in planning and performing experiments), S.K., A.A. , G.S. . All authors critically read and approved the manuscript.\u201d"} +{"text": "Unfortunately, we noticed that the reference list of our published paper containsTheileria annae as Babesia vulpes sp. nov. Parasit Vectors. 2015;8:207.8. Baneth G, Florin-Christensen M, Cardoso L, Schnittger L. Reclassification of We would like to apologize for this error and for any inconvenience this may have caused."} +{"text": "Leishmania in 165 samples collected from patients with CL in 16 provinces of Ecuador were examined at the species level based on the cytochrome b gene sequence analysis. Of these, 125 samples were successfully identified as Leishmania (Viannia) guyanensis, L. (V.) braziliensis, L. (V.) naiffi, L. (V.) lainsoni, and L. (Leishmania) mexicana. Two dominant species, L. (V.) guyanensis and L. (V.) braziliensis, were widely distributed in Pacific coast subtropical and Amazonian tropical areas, respectively. Recently reported L. (V.) naiffi and L. (V.) lainsoni were identified in Amazonian areas, and L. (L.) mexicana was identified in an Andean highland area. Importantly, the present study demonstrated that cases of L. (V.) braziliensis infection are increasing in Pacific coast areas.A countrywide epidemiological study was performed to elucidate the current geographic distribution of causative species of cutaneous leishmaniasis (CL) in Ecuador by using FTA card-spotted samples and smear slides as DNA sources. Putative Leishmania species, Leishmania (Leishmania) mexicana, L. (L.) amazonensis, L. (L.) major-like, L. (Viannia) guyanensis, L. (V.) panamensis, L. (V.) braziliensis, L. (V.) naiffi, and L. (V.) lainsoni, have been identified as causative agents of human cutaneous (CL) and mucocutaneous leishmaniases (MCL). Causative parasite species for CL have been identified as L. (V.) guyanensis, L. (V.) panamensis, L. (V.) braziliensis, and L. (L.) amazonensis in Pacific coast areas, L. (L.) mexicana and L. (L.) major-like in Andean highland areas, and L. (V.) guyanensis, L. (V.) braziliensis, L. (V.) naiffi, and L. (V.) lainsoni in Amazonian areas. In the present study, a countrywide epidemiological survey was performed to elucidate the current geographic distribution of causative species of CL in Ecuador, by using FTA card-spotted samples and smear slides as DNA sources. Putative Leishmania in 165 samples collected from patients with CL in 16 provinces of Ecuador were examined based on the cytochrome b gene sequence analysis. From these, 125 samples were identified, of which two dominant species, L. (V.) guyanensis and L. (V.) braziliensis, were widely distributed in Pacific coast subtropical and Amazonian tropical areas, respectively. Importantly, the present study demonstrated that cases of L. (V.) braziliensis infection are increasing in Pacific coast areas.In Ecuador, leishmaniasis is a major public health concern reported in 21 of 24 provinces of the country, and eight Leishmania, which is further divided into two subgenera, Leishmania (Leishmania) and Leishmania (Viannia). The disease is widely distributed around the world, especially in tropical and subtropical areas, affecting at least 12 million people in 98 countries , 19cyt bectively .Leishmania species, L. (V.) guyanensis, L. (V.) panamensis, L. (V.) braziliensis, and L. (L.) amazonensis have been reported as causative agents in subtropical areas in Ecuador, all the Leishmania samples from such areas in this study were identified as L. (V.) guyanensis and L. (V.) braziliensis, of which L. (V.) guyanensis was dominant (Leishmania (V.) braziliensis was identified in northern and central provinces (L. (L.) mexicana. In Amazonian tropical provinces , L. (V.) braziliensis was identified as the dominant species as reported previously [L. (V.) guyanensis, L. (V.) naiffi, and L. (V.) lainsoni were identified in this study; all were reported previously in Ecuador, the latter two rather recently [L. (V.) naiffi infection were identified in the previously reported area (Shangrila) in Orellana province, and L. (V.) lainsoni infections were identified in Sucumb\u00edos province. In the southern Amazonian province (Zamora-Chinchipe), only L. (V.) braziliensis was identified.In Pacific coast subtropical provinces , 61 of 101 samples (60.4%) were collected from Pichincha province. Although four dominant , Fig 1. \u00e1chilas) , Fig 1. eviously , 8, 9. Irecently , 8 (TablLeishmania (L.) mexicana infection in an Andean area caused a typical small ulcerative lesion (0.5cm), the so-called \u201cAndean-type CL\u201d [Leishmania species were observed.In the present study, all patients had typical ulcerative and/or nodular cutaneous lesions; none had mucosal or mucocutaneous lesions. The number of cutaneous lesions per patient ranged from one to six, and the diameter of lesions ranged from 0.5 to 5cm. The one type CL\u201d . No markcyt b gene analysis. Using minimally invasive sampling methods such as FTA card collections and smear slides, causative agents were successfully identified in 125 patients from 41 areas of 16 provinces in Ecuador. The results indicate that L. (V.) guyanensis and L. (V.) braziliensis are widely distributed in Pacific coast subtropical and Amazonian tropical areas, respectively. The data obtained also suggest that CL cases caused by L. (V.) braziliensis are increasing in Pacific coast areas. Distributions of L. (V.) naiffi and L. (V.) lainsoni, both of which have been identified recently in the Ecuadorian Amazon, were confirmed, and L. (L.) mexicana was identified in an Andean area.A countrywide survey was conducted to elucidate the current geographic distribution of causative species of CL in Ecuador on the basis of Leishmania species were identified in this study, previous studies reported distribution of three other species, L. (V.) panamensis and L. (L.) amazonensis in Pacific coast subtropical areas, and L. (L.) major-like in Andean highland areas in Ecuador [L. (V.) panamensis was identified by multilocus enzyme electrophoresis (MLEE) in Pacific coast areas [L. (L.) amazonensis, for which samples were not examined in this study, was identified from only a few areas [Leishmania (V.) panamensis is very closely-related to L. (V.) guyanensis, and a previous study questioned the distinctness of the two species by MLEE and genetic analyses of Leishmania isolates in Ecuador [L. (V.) panamensis and L. (V.) guyanensis were separated in distinct clades by phylogenetic analysis targeting the cyt b gene [L. (V.) panamensis or L. (V.) guyanensis by MLEE revealed discordant results among targeted genes, which is in agreement with a previous enzymatic and genetic analyses of the two species [L. (V.) guyanensis identified in this study includes Leishmania species previously identified as L. (V.) guyanensis and L. (V.) panamensis by MLEE. Since the present classification of Leishmania species has been defined by MLEE and genetic analyses of Leishmania suggested that the number of species could be very large, reclassification of Leishmania species including L. (V.) panamensis and L. (V.) guyanensis may be needed using extensive multiple genetic analyses [Leishmania (L.) major-like has been reported in Andean areas as a minor species causing CL [L. (L.) mexicana, the major causative species in Andean highland areas [cyt b gene sequence, which composes a separate clade from other L. (L.) mexicana strains including reference strains by a phylogenetic analysis [L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) naiffi, and L. (V.) lainsoni, were identified, of which distributions of the latter two species have been reported recently [L. (V.) lainsoni, the most recently reported species in Ecuador [L. (V.) naiffi were identified only in a military training camp at Shangrila, Orellana province, as reported previously [L. (V.) naiffi has been identified as Lutzomyia (Lu.) tortura in the same area [Lu. tortura by L. (V.) naiffi has also been detected in Arajuno, Pastaza province [L. (V.) naiffi have been reported in this area. It may be interesting to compare its transmission cycle, including reservoir animals and the vector\u2019s host preferences in the two areas to understand different occurrences of CL caused by L. (V.) naiffi.Although five Ecuador \u20135. Of thst areas , 5, wherew areas , 5. Leis Ecuador . Previout b gene , 25; how species . Therefoanalyses , 27. Leiusing CL ; howevernd areas \u20135. The canalysis , was conrecently . Distrib Ecuador , was recprovince , no humaL. (V.) guyanensis and L. (V.) braziliensis in Pacific coast and Amazonian areas. Wide distribution of the two species has been reported in other South American countries [Leishmania species. One of the most important findings of this study is that cases of L. (V.) braziliensis infection seem to be increasing in Pacific coast areas of Ecuador when compared to past studies [L. (V.) braziliensis and its sand fly vectors may be expanding in these areas. Alternatively, parasite isolation, which is required for MLEE, may be inefficient in L. (V.) braziliensis when compared to other species, resulting in fewer identifications of this species in past studies. The procedures for isolation of L. (V.) braziliensis parasites from patient\u2019s lesions and its maintenance/culture in vitro are very difficult compared to other Leishmania species because of the extremely limited presence of amastigotes in the lesions and/or maladaptation of the species to an artificial culture medium. Genetic analysis of directly sampled materials as conducted in this study can overcome this issue. Since infection by L. (V.) braziliensis is associated with destructive mucocutaneous lesions [The present study revealed wide distribution of ountries , reflect studies , 5. Dist lesions , continuLeishmania species. Together with prevalent parasite species, vector and reservoir research will be needed since this information is limited in Ecuador despite its importance for control of leishmaniasis.The present countrywide surveillance revealed the current geographic distribution of causative species of CL in Ecuador. The less-invasive and easy-to-use FTA card will be a useful tool for further continuous monitoring of prevalent S1 FigThe dark gray areas show the Andean plateau , and the light gray areas show highland jungle or Andean slopes . 1. Mataje, 2. Pampanal de Bol\u00edvar, 3. San Lorenzo, 4. Esmeraldas, 5. Atacames, and 6. Sabalito, Province of Esmeraldas; 7. Pedernales, 8. San Isidro, 9. Junin, 10. Jipijapa, and 11. Montalvo, Province of Manabi; 12. Manglaralto, Province of Santa Elena; 13. Cielo Verde, Province of Imbabura; 14. Puerto Quito, 15. Pedro Vicente Maldonado, 16. Los Bancos, 17. Nanegalito, 18. Pachijal, and 19. Quinche, Province of Pichincha; 20. Valle Hermoso, and 21. Chiguilpe, Province of Santo Domingo; 22. Balsapamba, Province of Bolivar; 23. Quevedo, Province of Los Rios; 24. Huigra, Province of Chimborazo; 25. La Troncal, Province of Ca\u00f1ar; 26. El Triunfo, 27. Naranjal, and 28. Balao, Province of Guayas; 29. Santa Rosa, Province of El Oro; 30. Cascales, 31. Lago Agrio, 32. Putumayo, and 33. Palma Roja, Province of Scumbios; 34. Coca, 35. Shangrila, 36. La Joya de los Sachas, and 37. Dayuma, Province of Orellana; 38. Puyo, and 39. Arajuno, Province of Pastaza; 40. Palanda, and 41. Zumba, Province of Zamora-Chinchipe.(TIF)Click here for additional data file.S2 Figcyt b genes were amplified and sequenced from patients with cutaneous leishmaniasis, and a phylogenetic analysis of cyt b gene sequences was performed by the neighbor-joining method together with sequences from 12 Leishmania species. The scale bar represents 0.01% divergence. Bootstrap values are shown above or below branches.Leishmanial (TIF)Click here for additional data file.S1 Checklist(DOC)Click here for additional data file."} +{"text": "P value<6.61 \u00d7 10\u22124), including a rare missensevariant in ABCA6, which is predicted to be deleterious.The frequency of this ABCA6variant is 3.65-fold increased in the Dutch and its effect is estimated to be very similar to thoseobserved for single variants in well-known lipid genes, such as LDLR.Variants associated with blood lipid levels may be population-specific. To identifylow-frequency variants associated with this phenotype, population-specific referencepanels may be used. Here we impute nine large Dutch biobanks with the population-specific reference panel created by the Genome of theNetherlands Project and perform association testing with blood lipid levels. Wereport the discovery of five novel associations at four loci ( Frequencies of rare variants fluctuate over populations, hamperinggene discovery. Here the authors use a population-specific reference panel, the Genomeof the Netherlands, to discover four novel loci involved in lipid metabolism, includingan exonic variant in ABCA6. Genome-wide association studies (GWAS) have identified a large number of loci associatedwith blood lipid levels and analysis suggest there are additional susceptibility locithat have not yet been discovered12123578http://www.nlgenome.nl/), in whichthe whole genomes of 250 parent\u2013offspring trios were sequenced at~13 \u00d7 coverage5Here we describe an imputation-based GWAS for circulating lipid levels using acustom-built reference panel for the Dutch population wereimputed with the GoNL reference panel (~19.5 million single-nucleotidepolymorphisms (SNPs)) on an identical protocol6N=60 variants), LDL-C (N=142 variants), TC (N=134variants) and TG (N=16 variants) in both known and novel loci to those reported in refs P value <3.18 \u00d710\u22124 despite a sample size of ~20% of the other studies.Both rare <0.01), low(0.010.05) were associatedwith HDL-C ,member 6). The frequency of this variant is 1.31-fold higher inthe discovery cohorts than in the replication cohorts and even 3.65-fold higher inthe GoNL population than in the 1-kG population. This missense variant changes theamino acid cysteine into arginine at position 1359 (Cys1359Arg) and is predicted tobe damaging for the structure and function of the protein by Polyphen2 (ref.\u03b2LDL-C=0.135 and \u03b2TC=0.140)is very similar to those observed for other single variants in well-known lipidgenes, such as LDLR andCETP, as reported inref. ABCA6 is clustered with four other ABC1 family memberson chromosome 17q24 and appears to play a role in macrophage lipid homeostasis.Of the replicated variants, rs77542162 is the most interesting variant. This missensevariant is associated with both LDL-C and TC and is len2 ref., Mutatiocis-eQTL effect, is located between theprotein-coding genes C17orf105 (chromosome 17open reading frame 105) and MPP3 . Two replicated variants have similarfrequencies in the GoNL and 1-kG reference sets: rs4752801 (MYO1F)-codinggene. C17orf15, MPP3 andMYO1F have no knownimpact on lipid levels. As the imputation quality of rs117162033 is lower than theother variants, we validated the imputation of this variant using the same approachas published in ref. MYO1F gene isremarkable because of the low frequency of the variant. This confirms theconclusions as published before about the GoNL reference panel, that the trio-basedphasing contributed significantly to the imputation quality of rare variantsOne other replicated variant, rs149580368, is also enriched with a 1.92-fold increasein frequency in the Dutch population compared with the 1-kG population. Thisintergenic variant , withouts4752801 , an new s4752801 , an intrIn this current study, the GoNL reference panel was used for imputations of thediscovery cohorts and the 1-kG reference panel for the imputation of the replicationcohorts. Although it would be interesting to impute with a combined reference panelof both the GoNL data, the 1-kG data and other sequence data, this effort isongoing.ABCA6, which hasincreased frequency 3.65 times larger in the Dutch population. The effect of thisvariant is comparable to that of variants in the LDLR gene, a gene for which severalpopulation-based screening programmes have been initiated. Our findings suggest thatnext-generation-sequencing effort may yield clinically relevant findings. Our paperfurther shows that next-generation-sequencing efforts in specific homogeneouspopulations as the Dutch may yield clinically relevant findingsworldwide.This study shows that the imputation of a population-specific reference panel intolarge epidemiological cohorts can reveal both low-frequency and rare variantsassociated with blood lipid levels using classical association testing approaches.The three variants with increased frequency in the Dutch population as compared withthe 1-kG population include a rare, predicted to be deleterious missense variant inThe descriptions of the including cohorts can be found in the A summary of the details of both the discovery and replication cohortsparticipating in this study can be found in Only samples of Dutch ancestry were used in the discovery cohorts; the samples inthe replication cohorts are from various ancestries see . In all The lipid measurements were adjusted for sex, age and ageDetailed information about genotyping and imputations per cohort can be found inthe \u03bb per trait per cohort and \u03bb per MAF bin per trait per cohort. We therefore used onlythe SNPs with a R2>0.3,R2<1.1 and expected minor allele count (expMAC=2\u00d7 MAF \u00d7 R2\u00b7sample size)>10. Most inflations are observed within the ERF study, especially in thelowest-frequency variants, which is probably caused by the family structure inthis cohort.All nine discovery cohorts ran separate the genome-wide association study foreach of the four traits: HDL-C, LDL-C, TC and TG. R2<1.1 and expMAC>10.The association results of all studies were combined and the s.e.-based weightswere calculated using METALP value less than 5\u00d7 10\u22128 for HDL-C, 2,626 SNPs for LDL-C, 3,133SNPs for TC and 1,310 for TG.After meta-analyses of all available variants, we excluded the variants that arenot present in at least six of the nine cohorts. We also excluded all variantsthat are labelled as being in the inaccessible genome, since the quality ofthose SNPs cannot be guaranteedet alet alet al\u22121, whereas in this studywe use mmol\u2009l\u22121. We therefore multipliedthe effect size for the loci associated with TG with 0.0259 and the other lociwith 0.011. Previously, Teslovich In order to select only associated variants that were independent of previousfindings, we used the GCTA toolR2<0.14).To identify potential novel variants, we first excluded all variants within1\u2009Mb of a known loci from refs \u22123. This resulted in the significantreplication of five out of the six variants, see The six potential novel loci were replicated in 11 cohorts: CHS, Croatia-Korcula,Croatia-Split, Croatia-Vis, FamHS, FHS, Generation Scotland, MESA Whites,ORCADES, PROSPER-Scottish and PROSPER-Irish. The association results of allcohorts were combined and the s.e.-based weights were calculated usingMETALWithin the discovery cohorts we performed a conditional analysis to see whetherthe novel variants are independent of the known loci from refs E.M.v.L. organized the study and designed the study with substantial input of L.C.K.,A.I., P.I.W.d.B. and C.M.v.D. E.M.v.L. drafted the manuscript with substantial inputof L.A.C., A.Me, B.M.P., C.W., G.M.P., J.F.W., J.E.H., L.C.F., L.C.K., J.D., P.E.S.,D.I.B., J.E.H., H.M., P.M.K., P.I.W.d.B., S.L.P., S.T., C.M.v.D. and G.-J.B.v.O. Allauthors had the opportunity to comment on the manuscript. Data collection, GWAS andstatistical analysis were performed by T.M.B., J.A.B., J.C.B., B.M.P. (CHS); J.E.H.,C.H., O.P., V.V., I.R., A.F.W. (CROATIA); E.M.v.L., B.A.O., C.M.v.D. (ERF); C.C.W.,L.A.C. (FHS), M.F.F., I.B.B. (FamHS); J.E.H., H.T., L.J.H., D.J.P. (GenerationScotland); G.M.P., Q.D., L.A.L. (JHS); A.Ma., J.I.R., J.C.M., S.S.R. (MESA); A.K.,P.D., F.v.D., M.A.S., C.W. (Lifelines); J.D., M.B., A.J.M.C., H.-W.U., P.E.S. (LLS);H.M., G.W., E.J.d.G., Y.M., B.W.J.H.P., J.-J.H., D.I.B. (NTR-NESDA); N.V., I.M.L.,P.v.H. (PREVEND); S.T., I.P., N.S., C.J.P., B.M.B., P.M.K., D.J.S., J.W.J.(PROSPER); P.K.J., H.C., J.F.W. (ORCADES); E.M.v.L., C.M.-G., F.R., A.H., O.H.F.,E.J.S., A.G.U., C.M.v.D. (Rotterdam Study). D.J.v.E. recruited cohorts. Creation ofthe GoNL reference panel was carried out by L.C.F., A.Me., S.L.P. and P.D. Design ofthe GoNL project was made by C.W., M.A.S., C.M.v.D., D.I.B., P.E.S., G.-J.B.O.,P.I.W.d.B. E.M.v.L. performed the meta-analysis. Biological association of loci andbioinformatics were carried out by E.M.v.L. and C.M.v.D.How to cite this article: van Leeuwen, E. M. et al Genome of theNetherlands population-specific imputations identify a ABCA6 variant associated with cholesterollevels. Nat. Commun. 6:6065 doi: 10.1038/ncomms7065 (2015).Supplementary Figures 1-19, Supplementary Tables 1-14, Supplementary Note 1,Supplementary Methods and Supplementary References"} +{"text": "Correct an error in the reference list. The correction does not affect the scientific validity of the results.Reference 14 in our paper is wrong:Refrence 14: Bussiere M., Vance J. E., Campenot R. B., Vance D. E. (2001). Compartmentalization of choline and acetylcholine metabolism in cultured sympathetic neurons. J. Biochem. (Tokyo) 130, 561\u2013568 10.1093/oxfordjournals.jbchem.a003019 is not correctCorrect one citation is:Cell Microbiol. 12, 1124\u20131133. doi: 10.1111/j.1462-5822.2010.01457.xBussi\u00e8re, F. I., Michel, V., M\u00e9met, S., Av\u00e9, P., Vivas, J. R., Huerre, M., et al. (2010). H. pylori-induced promoter hypermethylation downregulates USF1 and USF2 transcription factor gene expression. All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "During 2007\u20132010, on average, 4.7% of the daily calories consumed by U.S. adults aged \u226520 years came from alcoholic beverages. The percentage of daily calories from alcohol ranged from 6.5% for men aged 20\u201339 years to 2.1% for women aged \u226560 years. Across age groups, the percentage of calories from alcohol was higher among men; among both men and women, the percentage declined with age.Sources: National Health and Nutrition Examination Survey, 2007\u20132010. Available at http://www.cdc.gov/nchs/nhanes.htm.http://www.cdc.gov/nchs/data/databriefs/db110.htm.Nielsen SJ, Kit BK, Fakhouri T, Ogden CL. Calories consumed from alcoholic beverages by U.S. adults, 2007\u20132010. NCHS data brief, no. 110. Hyattsville, MD: US Department of Health and Human Services, CDC, National Center for Health Statistics; 2012. Available at"} +{"text": "There is an error in the citation only within the PDF of the published article. The last author in the citation should be Natale P. The correct citation is:Pazos M, Casanova M, Palacios P, Margolin W, Natale P, et al. (2014) FtsZ Placement in Nucleoid-Free Bacteria. PLoS ONE 9(3): e91984. doi:10.1371/journal.pone.0091984"} +{"text": "Tunga, complementing the previously published data on the phylogeny, ecology, and pathogenic role. Neosomes are structures formed after penetration of adult females into the skin of hosts resulting in significant enlargement, being the most characteristic and most frequently observed form in hosts. Neosomes can be differentiated by shape, measurements, and sites of attachment to principal hosts. The taxonomic value and morphometric data of the most widely used characteristics to separate species \u2013 such as frontal curvature, head chaetotaxy, preoral internal sclerotization, ventral and dorsal genal lobes, eyes, maxillary palps, fusion of pronotum and mesonotum, metacoxae, metatarsi chaetotaxy, spermatheca , manubrium, basimere, telomere, and phallosome \u2013 are comparatively analyzed. The sexes, individual variations, undescribed species, higher taxa, as well as a proposal for division of the genus into two subgenera (Tunga and Brevidigita) are presented (as previously given by Wang). A key for females, males, and gravid females (neosomes) also is included for identifying the 13 known species. Data on host specificity and geographical distribution may also support the identification of Tunga species because some sand fleas and their hosts may have co-evolved.This review focuses on the neosomes, morphology, and taxonomy of adult species of the genus Tunga comprises 13 species, representing less than 0.5% of the world flea fauna, which consists of approximately 3,000 known species [T. penetrans [T. caecigena Jordan and Rothschild, 1921 [T. callida Li and Chin, 1957 [T. monositus Barnes and Radovsky, 1969 [T. caecata [T. libis Smit, 1962 [T. bossii De Avelar, Linhares, and Linardi, 2012 [T. bonneti Beaucournu and Gonz\u00e1lez-Acu\u00f1a, 2012 [T. travassosi Pinto and Dreyfus, 1927 [T. bondari Wagner, 1932 [T. terasma Jordan, 1937 [T. trimamillata Pampiglione, Trentini, Fioravanti, Onori, and Rivasi, 2002 [T. hexalobulata De Avelar, Facury Filho and Linardi, 2013 [Currently, the genus species . One spe., 1758) , present., 1758) , Europe ., 1758) , and New., 1758) in whom ld, 1921 and T. cin, 1957 , parasitky, 1969 , 37: T. n, 1901) ; T. libiit, 1962 ; T. boss\u00f1a, 2012 , 34: T. us, 1927 ; T. bonder, 1932 and T. tan, 1937 ; and twoan, 1937 , 39, 41:si, 2002 ; and T. di, 2013 . It is iTunga is the most specialized genus because the adult females penetrate into the skin of their hosts. Similar to other fleas, both males and females are blood-feeding [T. monositus do not feed [Among the Siphonaptera, -feeding , 53, hownot feed .Tunga concerning taxonomy, phylogeny, ecology and pathogenic role was presented by Beaucournu et al. [T. hexalobulata, which was described subsequently. Similarly, De Avelar et al. [T. bossii for the first time, presented a widely used dichotomous key for identifying the known species and their neosomes and excluded T. bonnetti and T. hexalobulata, which were discovered later.Recently, a review of the genus u et al. , althougr et al. , when deTunga species, including a more classical vision and emphasizing neosomal characteristics.The present study complements this review with regard to the neosomes, morphology, classification, and other taxonomic notes. The taxonomic value and morphometric data of several characteristics are comparatively analyzed. Although the morphological aspects are often not known for many taxa, here we present a new key for identifying the 13 known Neosomes are altered organisms resulting from a process characterized by the growth of new tissue and the formation of a new morphological structure accompanied by significant enlargement after adult eclosion . This phTunga (Tungidae) and Neotunga (Pulicidae); (ii) an external, sessile female, permanently attached as soon as it is on its host (ectoparasites): Echidnophaga (Pulicidae), Hectopsylla (Tungidae); or (iii) an external, non-sessile female, temporarily attached when on its host: Chaetopsylla pro parte, Dorcadia, Vermipsylla (Vermipsyllidae), Parapsyllus pro parte , Glaciopsyllus (Ceratophyllidae), Ancistropsylla (Ancistropsyllidae), Malacopsylla and Phthiropsylla .Approximately 90 species of fleas have sessile or semi-sessile females that, after eclosion, remain more or less permanently attached to the integument of the host . ConsideTunga have concentrated on the description of the neosomes because they are the most characteristic and most frequently observed form in hosts. Females and males measure approximately 1\u00a0mm, but after penetration, the gravid females increase considerably in size, reaching approximately 10\u00a0mm conical, as in T. caecata, T. travassosi, T. trimamillata, and T. hexalobulata; or (iii) cylindrical, as in T. terasma, T. bondari, T. caecigena, and T. callida. Otherwise, the caudal disk can be (i) as wide as long, or almost as wide as long, as in T. caecata, T. travassosi, and T. callida; (ii) wider than long, as in T. penetrans, T. monositus, T. trimamillata, T. bossii, and T. hexalobulata; or (iii) longer than wide, as in T. terasma, T. bondari, and T. caecigena. Neosomes can live more than three months attaching to different sites of their respective hosts [Tunga.Morphological studies of the genus ly 10\u00a0mm , and expenetrans , T. monove hosts , 26. ConA review solely on the neosomes of tungid fleas that infest wild and domestic animals and concentrated mainly on hosts, infestation, sites of attachment, and impact on the hosts was recently presented by Linardi and Avelar .Tunga species with their respective geographic distributions, sexes, stages, neosomes, and sites of attachment to principal hosts. Excepting neosomes, in which the size is indicated in millimeters, all measurements included in other tables are in micrometers.Tunga are discussed as follows:Excepting neosomes, the classical structures more frequently used to separate or group the species of cephalic capsule includes the majority of the characteristics used for identifying these species. Members of the genera Tunga, Hectopsylla , Echidnophaga, Phacopsylla, and Neotunga euloidea are always characterized by an angular profile and a well-pronounced frontal tubercle, as in T. caecigena or with the posterior arm subequal to or shorter than the anterior arm , or much shorter than the anterior arm . A dorsal genal lobe either covers part of the antennal segment III or not, as in other species. The number of bristles on the postantennal region, posterior region to the frontal tubercle, antennal segment II, and base of the maxilla may be a differential characteristic. Inside the cephalic capsule, the eyes are the most characteristic structures for species identification. They may be absent in caecigena and callida or present in other species, or they may be pigmented or without black pigment . When present, the eyes can be small , or large, in the case of other species. In some species such as penetrans, bondari, trimamillata, the eyes also have a recess into their internal margins. The greatest eye diameters and the numeric variations of bristles on some structures of Tunga species are presented in The aecigena , T. travavassosi , T. bond bondari , T. trimamillata , T. boss. bossii , and T. lobulata . The froaecigena or almosT. libis . Generalcaecigena, callida, and bonneti, segment IV is longer than segment I, though the reverse is true in T. trimamillata and T. hexalobulata. In other species, the palps are approximately the same length. In T. bossii, segment I was described as very small and segments III and IV as being incompletely divided; however, a new observation showed that, in fact, what was thought to be \u201csegment I\u201d was a strengthened area at the base of the palp and an incomplete division occurred between segments II and III and between segments III and IV.Maxillary palps with segT. bossii, laciniae and preoral internal sclerotization are indicated in Morphometric data regarding the maxillary palps, including new measurements for fusion of the pronotum and mesonotum can be dorsally complete, a characteristic of the penetrans group or incomplete, as in the caecata group. Currently, the penetrans group includes T. penetrans, T. travassosi, T. bondari, T. terasma, T. trimamillata, and T. hexalobulata [caecata group, the following species are included: T. caecata, T. caecigena, T. callida, T. libis, T. monositus, T. bossii, and T. bonneti. The chaetotaxy is generally sparse, consisting of 1\u20137 bristles on the prothorax. Legs III show the classical increase in length, compared to the first two pairs, typical of Siphonaptera. However, these legs are slender, and members of the Tunga genus are poor jumpers despite the existence of a pleural arch. At this leg, Beaucournu et al. [coxae are always preserved regardless of the autotomy of the legs. The metacoxae or thick . The measurements of the bulga and hilla of the spermathecae are presented in segment IX (clasper) and the phallosome are the most striking features for differentiating species. Similar to other fleas, segment IX is divided into two processes, the basimere and the telomere which are connected to another structure, the manubrium. phallosome consists of proximal and distal arms articulated in the middle, just before the ductus ejaculatorius and is almost as long as the penis-plate.In males, T. penetrans and T. monositus, the two arms are angled at approximately 90\u00b0, whereas in T. callida and T. caecigena, they are connected in a nearly straight line. The size ratio and the angle between the two arms are differential features for the species, as seen in The principal synonymies, sexes, individual variations, undescribed species, subgenera, higher taxa and a key for adult species and neosomes are included and discussed below.T. penetrans presents seven major synonyms followed by T. caecata with two of them. All the synonymies for the genus were already cited by Beaucournu et al. [It is interesting to note that the older the description of the species, the greater the number of existing synonymies. Thus, u et al. .caecata, travassosi, bondari, bossii, and hexalobulata are known only through their hypertrophied females. T. penetrans, T. callida, T. monositus, T. trimamillata, and T. bonneti are species in which the holotype and the allotype were described simultaneously. In caecigena and libis, the allotype males were described 37 (1958) and 6 (1968) years, respectively, after the holotype females. The males of T. terasma were described incorrectly by Fonseca [T. travassosi. Interestingly, the holotype female of T. terasma was described the following year by Jordan. It is possible that this is the only case in the entire order of Siphonaptera in which the allotype was known before the holotype.As shown in Fonseca as malesT. penetrans and T. terasma. The illustrations of the male of T. caecigena presented by Chen and Ku [T. caecigena. Similarly, when describing T. monositus, Barnes and Radovsky [Regardless of sexual dimorphism , most of the individual variations are found in the modified segments, especially among the males. Hopkins and Rothschild illustran and Ku also shon and Ku stress vRadovsky illustracaecata group were observed by Linardi and Botelho [Oryzomys nigripes (currently Oligoryzomys nigripes) and Nectomys squamipes from Caratinga, Minas Gerais State, Brazil, with the neosomes located near the base of the dorsal surface of the ears. The neosomes of O. nigripes are spherical and 8\u20139\u00a0mm in diameter, in contrast to those observed in N. squamipes that present three anterior humps and measure 8\u00a0mm in diameter eine Hausmaus (= Mus musculus), die 13 solcher Fl\u00f6he an einem und 12 am anderen Ohr hatte\u201d (He showed me a house mouse (Mus musculus) in Lagoa Santa that had 13 of these fleas on one ear and 12 on the other). Burmeister and Reinhardt apparently caught sight of the two Tunga parasites of rodents in Brazil, caecata and bossii!Beaucournu et al. commente by Smit , who wroT. bonneti. Subsequently, Frank Radovsky, one of the authors of this work , reported that \u201cIncidentally, I have preserved material of Tunga in Phyllotis from Peru which I hope to describe. There are 2 undescribed species, one on the ear pinna as in T. monositus and your Tunga and one in the tail!\u201d However, these two species were ultimately not described by Radovsky. Given the morphological similarities, the hosts, and geographical distribution, it is possible that these two species were, in reality, T. libis and T. bonneti!When defining neosomy, Audy et al. includedTunga and belonging to the \u201cpenetrans group\u201d was found in Argentina [e-mail, May 30, 2014 addressed to P.M. Linardi) reported that this species is now being described and that it forms a discoid neosome in the carapace of Zaedyus pichiy perforating the osteoderms.A new species of rgentina . SubsequTunga into two groups of species, he considered morphological characteristics such as the dorsal fusion of the pronotum and the mesonotum, the chaetotaxy of the fifth tarsal segment and the presence or the size of spiracular fossae on terga II\u2013IV of the females, in addition to the parasitized host groups. At that time, only eight species were known. Four were included in the penetrans group and four others in the caecata group . Later, another proposal by Wang [caecigena and callida, in a distinct subgenus (Brevidigita). When presenting the supraspecific classification for the genus Tunga, Lewis [Tunga species that parasitize commensal rats for inclusion in Brevidigita because only T. caecata was added, though two other species, T. monositus and T. libis, were already known and were improperly left in the subgenus Tunga. Currently, with 13 known species, we consider the genus divided into two subgenera, Tunga and Brevidigita, though this division may be debatable:Tunga: T. (T.) penetrans, T. (T.) travassosi, T. (T.) bondari, T. (T.) terasma, T. (T.) trimamillata, and T. (T.) hexalobulata.Subgenus Brevidigita: T. (B.) caecata, T. (B.) caecigena, T. (B.) callida, T. (B.) libis, T. (B.) monositus, T. (B.) bossii, and T. (B.) bonneti.Subgenus When Smit divided by Wang , based sa, Lewis acceptedTunga, these rules are not respected. As has been done in the genus Pulex , further divisions may be required when the puzzle of taxa known as Tunga is complemented by a comparative study of all males.The vast majority of the Siphonaptera show a certain consistency for certain wildcard characteristics; for example, the profile of the cephalic capsule, development of the eye (unless a host to a different ecology), the proportions of the various articles of the palp, or the form of the spermatheca. However, in the genus in Aberlenc) [insect holometabolous, wingless larvae apoda detritiphages but with mandatory addition of blood in their diet in adulthood latero-lateral, flattened to hind legs longer than the 2 prior to biting mouthparts (hematophagous regime), size ranging, fasting and/or before fertilization, from 0.75 to 8 mm. Now, we are also including \u201cbristles directed backward and brownish colour\u201d.\u201c- During copulation, the male is always under the female. The phallosome has no middle joint, except in Hectopsylla. The female is vagile, more rarely sessile, and never cystic in the dermis of the host ; the female\u2019s spermatheca is completely visible before any meal or copulation; the male\u2019s abdomen may become neosomic, but it will always remain outside the host (except in N. euloidea); the abdominal spiracles do not change in shape, size or location during the life of the imago even in the case of neosomy\u2026 Pulicoidea, Vermipsylloidea, Malacopsylloidea, Ceratophylloidea and Hystrichopsylloidea- During copulation, the male is always on the female. The phallosome presents a middle joint. The female is vagile only while searching for a host, and upon finding one it becomes completely encapsulated; the female\u2019s spermatheca is visible in its entirety, only when encapsulated (bulga and hilla); female neosomy is very important and compulsory; abdominal stigma in the neosomes, are very enlarged and displaced and form on the terminal tergites\u2026 TungoideaBeaucournu (berlenc) ) recogniTunga. Hectopsylla remains in the Pulicoidea. Linardi asserts that Heanalysis .allida, libis, monositus, trimamillata, bossii, bonneti, and hexalobulata). While it is no longer usable, it proposed to differentiate Tungidae, but using characteristics that have proved worthless, for example, the indentation of the eye. This same key, excluding the two Chinese Tunga, was later reproduced by Johnson [T. monositus, presented a key exclusively for the caecata group species known at that time.The first dichotomous key for this genus was that of Hopkins and Rothschild and did Johnson to ident Johnson , when deTunga bossii, proposed a new key, including all known taxa in which the appearance of the neosome is widely used. Although often the morphological aspects of many taxa that we would like to use in classification are not known , we attempt to provide a more classical vision of differentiation, with emphasis on independent characteristics of neosomes. Thus, this new key also includes the means to differentiate known male characteristics.Recently, De Avelar et al. , when deTunga) ..............................................................................2Pronotum and mesonotum fused dorsally. Fifth tarsomere of the metatarsus with chaetotaxy reduced and exhibiting only two pairs of lateral plantar bristles . Males hBrevidigita)........................................................................7Pronotum and mesonotum not completely fused dorsally. Fifth tarsomere of the metatarsus with chaetotaxy not reduced and exhibiting more than three pairs of lateral plantar bristles . Males hT. (T.) travassosi Pinto and Dreyfus.Eye without black pigment . Base ofEye pigmented . Base of maxilla with two or more bristles. Neosome with head not invaginated within abdomen or laterally visible........................................................................3T. (T.) bondari Wagner.Eye small, its greatest diameter only slightly exceeding half the distance from eye to dorsal margin of head . Dorsal Eye large, its greatest diameter nearly equal to the distance from eye to dorsal margin of head. Dorsal genal lobe not covering the antennal segment III. Segment I of maxillary palp longer than segment IV. Spermatheca with a bulga longer than wide. Neosome globular or with prominent lobes.................................................................................................................................................4T. (T.) terasma Jordan.Frontal tubercle slightly pronounced . AntennaFrontal tubercle conspicuous . AntennaT. (T.) penetrans (L.).Head with pronounced ventral genal lobe . AnterioHead with no evidence of ventral genal lobe . AnterioT. (T.) trimamillata Pampiglione, Trentini, Fioravanti, Onore, and Rivasi.Head with the postantennal region exhibiting 17\u201319 bristles . AntennaT. (T.) hexalobulata De Avelar, Facury Filho, and Linardi.Head with the postantennal region exhibiting nine bristles . AntennaEye absent. Males with the basal and apical tubes of the phallosome articulated almost in a straight line .........Eye present. Males with the basal and apical tubes of the phallosome forming a right angle .........T. (B.) caecigena Jordan and Rothschild.Occipital region with 8\u201310 bristles . PreoralT. (B.) callida Li and Chin.Occipital region with 3\u20135 bristles . PreoralEye pigmented. Head with the frontal curvature almost straight . ManubriEye without black pigment. Head with the frontal curvature gently convex . ManubriT. (B.) libis Smit.Fifth metatarsomere with numerous minute plantar bristles . SegmentT. (B.) bonneti Beaucournu and Gonz\u00e1lez-Acu\u00f1a.Fifth metatarsomere of the metatarsus with few minute plantar bristles . SegmentT. (B.) monositus Barnes and Radovsky.Posterodorsal lobe of proepimeron large, strongly projecting. Base of maxilla with no bristles. Metacoxa with basal portion much wider than apical and with anterior basal corners dilated . SpermatPosterodorsal lobe of proepimeron small, rounded. Base of maxilla with one or two bristles. Metacoxa with basal portion a little wider than apical and without dilatation in the anterior basal corners . SpermatT. (B.) caecata (Enderlein).Preoral internal sclerotization with posterior arm more than eight times the length of anterior arm . FrontalT. (B.) bossii De Avelar, Linhares, and Linardi.Preoral internal sclerotization with posterior arm less than four times the length of anterior arm . ConspicTunga is concentrated in South America, including 77% of the species that most likely originated there. Because approximately 23% of the species were described in the last 2\u00a0years from Ecuador, Brazil, and Chile, the biomes and regions contained in these countries offer great opportunities for new findings. There are at least three or four undescribed species, with one of them awaiting description and another two or three remaining confused with species that are already known.The geographical center of the distribution of the genus Thirty-nine percent of the species are known only by the characteristics of the embedded females (neosomes). Only two out of the 13 described species of sand fleas have known larvae, although several larvae of the 1st instar of an undescribed species were obtained in the laboratory by Linardi and Botelho from hypBecause larval development occurs in fine-grained soils and the sand fleas are univoltine, the best results can be obtained in the dry-cool season.T. penetrans and T. trimamillata, which infest both domestic animals and humans, the correct identification of species is indispensable. T. penetrans has been found parasitizing at least 28 genera of hosts [Given the epidemiological and economic importance of of hosts , althougof hosts , 33. Morof hosts the MultRodents and edentates are the main hosts of Siphonaptera, housing approximately 85% of the known species.Tunga species because some sand fleas and their hosts may have co-evolved. According to Traub [Tunga at the base of flea phylogeny and its association with basal mammal hosts suggests that the origin and diversification of Siphonaptera coincided with basal mammal diversification. Sloths (Pilosa) and armadillos (Cingulata) belong to an ancient stock of mammalians and constitute the majority of the natural mammalian hosts of the genus Tunga [Data on host specificity and geographical distribution may support the identification of to Traub , most flto Traub . Mammalsto Traub placed Tus Tunga .No conflict of interest."} +{"text": "AbstractHoffmannanthus with one species and with Vernonia brachycalyx O. Hoffm. as type, and Jeffreycia with five known species, with Vernonia zanzibarensis Less. as type. Vernonia abbotiana O. Hoffm. is neotypified and is an older name for V. brachycalyx.Two genera of Vernonieae subtribe Erlangeinae with Type A pollen, 5-ribbed achenes, and blunt-tipped sweeping hairs on the styles are described as new, PageBreakVernonia Schreb. in the Old World was begun by Vernonia native to the Eastern Hemisphere. The genus Vernonia is almost entirely North American and Hoffmannanthus also share an unusual type of glaucolide derivative that has otherwise been reported only from Bothriocline (as Bothriocline amplifolia), all three genera evidently members of the Erlangeinae in the strict sense.The genera equenced . The ava H. Rob. , and som H. Rob. , 2009. OErlangeinae with the genera PageBreakErlangea Sch. Bip., Bothriocline Oliv. ex Benth., and Cyanthillium Blume consists of herbaceous plants with mostly lophate, triporate pollen, symmetrically T-shaped hairs, and sharply pointed sweeping hairs on the styles. In contrast, the two genera described herein are shrubbier or weakly arborescent with sublophate, tricolporate pollen having a continuous perforated tectum between the colpi, simple or asymmetrical non-T-shaped hairs, and blunt tips on the sweeping hairs.The typical element of the subtribe Hoffmannanthus and Jeffreycia H. Rob., S. Keeley & Skvarla have short petioles and blades with auricles projecting laterally at the base Spach. Vernonia brachycalyx was not treated in the first effort to resolve palaeotropical Vernonieae by Hoffmannanthus are considered to be particularly close to Jeffreycia which was placed by Vernonieae, the sweeping hairs in Hoffmannanthus are lacking on the upper shaft of the style, but unlike most Jeffreycia, are not lacking on the bases of the style branches. Both genera are most common in east Africa. It is concluded that the two genera described here as new are closely related to each other but distinct.PageBreakPageBreakPageBreakJeffreycia, includes three of the species mistakenly placed in Gymnanthemum in the subtribe Gymnantheminae by Gymnanthemum of a broad abaxial shield in the involucral bracts and the tendency for the inner involucral bracts to be deciduous in Gymnanthemum, instead of persistent as in Jeffreycia.The second genus treated here, PageBreakJeffreycia is the recently described Uniyala H. Rob. & Skvarla of India and Sri Lanka .Scrambling shrubs; stems slender with solid pith, somewhat deflected at nodes in upper part of vegetative plant and in inflorescence; hairs of stems L-shaped, with long, multicellular, uniseriate stalk and elongate, horizontal cap cell mounted near one end. Leaves alternate, petioles slender and 7\u201315 mm long below basal acumination of blade; blades ovate, 6\u20137 times longer than petiole, 5\u201310 cm long, 1.5\u20135.0 cm wide, base broadly obtuse to short-acute, narrowly acuminate at petiole, margins remotely denticulate to nearly entire, apex scarcely to gradually acuminate, surfaces pilosulous and Hoffmannanthus is considered appropriate, since both of the older species names featured here were published by The name The genus contains the single species.Taxon classificationPlantaeAsteralesAsteraceae(O. Hoffm.) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140772-1Vernonia abbotianaAbbot 1890 (holotype B destroyed). Neotype (selected here): Tanzania, Kwa Mshusa, May 1893, Holst 9096 . O. Hoffm., Bot. Jahrb. Syst. 20: 221. 1894. Type: Tanzania, Kilimandjaro, Vernonia brachycalyxHolst 9096 . O. Hoffm. in Engler, Pflanzenw. Ost-Afr. C: 405. 1895. Type: Tanzania Kwa Mshusa, Vernonia meiocalyxDelamere s.n. (syntypes BM). S. Moore, J. Bot. 38: 155. 1900. Type: Kenya, Vernonia hoffmanniana S. Moore, J. Bot. 38: 156. 1900, nom. nud.Vernonia jodopappaVernonia jodopapposa Lanza, Miss. Biol. Borana, Racc. Bot. Angiosp.-Gymnosp.: 244. 1939. Type: Kenya, Nyeri, Balbo 428 . Chiov., Racc. Bot. Miss. Concol.: 60. 1935, nom. illeg., non Sch. Bip. 1845. The species occurs from Ethiopia, Congo and Uganda in the north to Angola, Malawi and Zambia to the south.PageBreakVernonia abbotiana O. Hoffm. was destroyed in Berlin during the Second World War, and the species was treated by A. Peter OI 119, from Tanzania, Usambara, collected May 25, 1914, identified as Vernonia abbotiana, was deposited in the US. National Herbarium. Although not a type, the specimen led to a careful comparison with the original description of the species H. Rob. The latter species is not a close relative, but the reference to it in the original description indicates the kind of dense inflorescence. Such a dense inflorescence is unlike that in the Peter specimen, but it is very like typical material of Vernonia brachycalyx with which the Peter specimen is now identified. The identification might never have been made without the advent of the Peter specimen, but names such as Vernonia abbotiana, dating from comparatively early in the study of tropical Africa, do need to have their identity resolved by some means, in this case by neotypification. Personally, there is no doubt of the identification provided here, and a neotype, that is an isolectotype of Vernonia brachycalyx at the US National Herbarium is selected and Vernonia stuhlmannii O. Hoffm. (1898) are described with leaf bases truncate to subcordate, and both species are probably members of Jeffreycia, distinguished from the others by the appendages on the tips of their involucral bracts. However, Vernonia brucaea is described with \u201cfoliis ellipticis vel lanceolatis basi late cuneatis vel rotundatis\u201c. Not stated is whether that leaf base is as abrupt at the insertion on the petiole as in all the species of Jeffreycia recognized here, and any close relationship to Jeffreycia is doubtful.In addition to the species listed below, Vernonia zanzibarensis Less. that have longer petioles. Some specimens combine long hairs at the apices of the corolla lobes as in Vernonia zanzibarensis with panduriform bases on short-petiolate leaves, and it is apparently plants like these that have been interpreted by Vernonia hildebrandtii Vatke. However, it is possible that such leaf blades are just a variant of Vernonia zanzibarensis that has reverted to or retained the leaf form that is characteristic of all the other members of the genus.Regarding the shape of the leaf base, while it is similar to cordate, Taxon classificationPlantaeAsteralesAsteraceae(Muschl.) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140773-1Vernonia amaniensisZimmerman & Warnecke 90 . Muschl., Bot. Jahrb. Syst. 46: 78. 1911. Type: Tanzania, Amani, Tanzania.PageBreakTaxon classificationPlantaeAsteralesAsteraceae(Vatke) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140774-1Vernonia hildebrandtiiGymnanthemum hildebrandtii (Vatke) H. Rob., Proc. Biol. Soc. Washington 112(1): 241. 1999. Type: Tanzania, Zanzibar, Hildebrandt 1020 . Vatke, Oesterr. Bot. Z. 25: 323. 1875. Vernonia tayloriiTaylor s.n. (holotype BM). S. Moore, J. Bot. 38: 154. 1900. Type: Kenya, Rabai Hill, Kenya, Somalia, Tanzania.Taxon classificationPlantaeAsteralesAsteraceae(O. Hoffm.) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140775-1Vernonia usambarensisHolst 9146 & Tanzania, Mlalo, Holst 129, 203 (syntypes B destroyed). O. Hoffm., Bot. Jahrb. Syst. 20: 220. 1894. Type: Tanzania, Kwa Mshusa, Tanzania.Taxon classificationPlantaeAsteralesAsteraceae(Less.) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140776-1Vernonia zanzibarensisGymnanthemum zanzibarensis (Less.) H. Rob., Proc. Biol. Soc. Washington 112(1): 243. 1999. Type: \u201cBojer in insula Zanzebar (v. sp. in hrb. Horn.)\u201d \u201d .Kenya, Tanzania.Taxon classificationPlantaeAsteralesAsteraceae(L.) H. Rob., S.C. Keeley & Skvarlacomb. nov.urn:lsid:ipni.org:names:77140777-1Eupatorium zeylanicumVernonia zeylanica (L.) Less., Linnaea 4: 344. 1829. Gymnanthemum zeylanicum (L.) H. Rob., Proc. Biol. Soc. Washington 112(1): 243. 1999. Type: Herb. Hermann 4: 22 . The previous lectotype designation ( L., Sp. Pl.: 837. 1753. ignation : 131 refSri Lanka.PageBreakHoffmannanthus and Jeffreycia. We also thank Ingrid Pol-yin Lin of the Department of Botany for the scan of the isolectotype of Vernonia brachycalyx O. Hoffm. designated here as the neotype of Vernonia abbotiana O. Hoffm. Thanks also to the editor, Alexander Sennikov, for many careful observations and corrections.We wish to thank Alice Tangerini, Staff illustrator of the Department of Botany, National Museum of Natural History for the line drawings of the leaves and corollas of"} +{"text": "AbstractPiptochaetium fuscum, is provided for a taxon hitherto known as Piptochaetium setosum (Trin.) Arechav. Morphological, anatomical, and molecular studies that argue against including Piptochaetium in Stipa, and hence use of S. purpurata (Phil.) Columbus & J.P. Sm., are cited.A new name, PageBreakPiptochaetium setosum (Trin.) Arechav. was superfluous and illegitimate at the time of publication because its basionym, Urachne setosa Trin., was itself superfluous and illegitimate at the time of publication, Trinius having included in it two older and validly published names, Stipa panicoides Lam. and Oryzopsis setacea Rich. Stipa panicoides is the basionym of Piptochaetium panicoides (Lam.) Desv., a taxon that is now considered distinct from Piptochaetium setosum Columbus & J.P. Sm. , Piptochaetium purpuratum Phil. Barkworth, Ciald., & Gandhicomb. nov.urn:lsid:ipni.org:names:77136235-1http://species-id.net/wiki/Piptochaetium_fuscumUrachne fusca Nees ex Steud., Syn. Pl. Glumac. 1(2): 123. 1854 [1855 publ. 2\u20133 Mar 1854]. Lectotypus: K000433539, Herbarium Hookerianum 1867 (http://specimens.kew.org/herbarium/K000433539), imaginem videmus; Isolectotypi K000433540, Herbarium Benthianum 1854 (http://specimens.kew.org/herbarium/K000433540), imaginem videmus; CGE, Herb. J. Lindley, purchased 1866 ; \u201cprope Valparaiso, Chili; H. Cuming 453, 1831; Imagines videmus.PageBreakPageBreakPiptochaetium purpuratum Phil. because the name Stipa fusca had already been used for an Australian taxon by The three specimens are from the same gathering and conform to the protologue. We chose K000433539 as the lectotype because it has more material, both reproductive and vegetative, than the other specimens. Piptochaetium fuscum grew in central Chile, extending from Valparaiso and Santiago to Valdivia. This statement was confirmed by 37.41S, 72.01W [SI 268952]; 36.48S, 72.71W [BAA 416344], and 36.56S, 72.49W [BAA 416345]. Piptochaetium fuscum, a search should be made for specimens in Chilean herbaria and field work conducted to locate natural populations. Such activities were beyond the scope of our study.To determine the conservation status of PageBreak"} +{"text": "R. Soc. open. sci.3, 150526. . (doi:10.1098/rsos.150526)Amendment to table 2The first few rows are amended so that the table is now in line with figure\u00a04 and corresponds to the text. Additionally, it highlights that Nottingham, Cardiff, Sheffield, Bristol and Manchester are alike cities."} +{"text": "N. espei, N. limatus, and line 17 incorrectly contains the name N. rubrotaniatus instead of N. rubrocaudatus. The authors have provided a correct version of"} +{"text": "Scientific Reports6: Article number: 2707410.1038/srep27074; published online: 06012016; updated: 07252016This Article contains errors in the Author Contributions Statement.\u201cConceived and designed the experiments: W.Y.Z. and W.T.Q. Performed the experiments, analyzed the data and wrote the paper: W.T.Q. Revised and approved the final version of the paper: W.Y.Z\u201d.should read:\u201cConceived and designed the experiments: W.Y.Z. Performed the experiments, analyzed the data and wrote the paper: W.T.Q. Revised the manuscript and approved the final version of the paper: W.Y.Z\u201d."} +{"text": "In the above editorial the following reference:Front. Hum. Neurosci. 9:176. doi:10.3389/fnhum.2015.00176Breiter, H. C., Viswanathan, V., Lee, S., Gilman, J. M., Kim, B. W., Lee, N., et al. (2015a). Age-related striatal BOLD changes without changes in behavioral loss aversion. Was incorrectly cited and should have been reported as:Front. Hum. Neurosci. 9:176. doi:10.3389/fnhum.2015.00176Viswanathan, V., Lee, S., Gilman, J. M., Kim, B. W., Lee, N., Chamberlain, L., et al. (2015). Age-related striatal BOLD changes without changes in behavioral loss aversion. Accordingly, the citation Breiter et al. (2015a) in paragraph 10 should read Viswanathan et al. (2015), and, as a consequence, the citation (same paragraph) Breiter et al. (2015b) should read Breiter et al. (2015). This error occurred due to the fact that an outdated author list on this respective citation was originally processed and this Corrigendum serves to correct this.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The age-adjusted death rates for stroke in all U.S. Census regions in the United States generally decreased from 1970 to 2013, although the rates in all regions were relatively stable from 1992 to 1999. From 1970 to 2013, the rate decreased an average of 3.3% per year in the South, 3.2% in the Midwest, 3.3% in the West, and 3.4% in the Northeast. Throughout the period, the rate was the highest in the South and lowest in the Northeast region.Source: National Vital Statistics System. Mortality public use data files, 1970\u20132013. Available at http://www.cdc.gov/nchs/data_access/vitalstatsonline.htm.Reported by: Jiaquan Xu, MD, jax4@cdc.gov, 301-458-4086."} +{"text": "Please refer to the complete funding statement below:This work was supported in part by DFG grant SPP 1230 (A.E.), the E-rare project Transposmart (A.E. and Z.I.), the Wilhelm Sander-Foundation (A.E.), EU Framework Programme 7 (Persistent Transgenesis) (A.E), and the Friedrich-Baur-Foundation (A.E.). W.Z. was supported by a fellowship from the Chinese Scholarship Council (CSC) in cooperation with Northwest A&F University, Yangling, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."} +{"text": "AbstractWoodsia is presented, as a part of a taxonomic revision of the genus in South America. Lectotypes are selected for Cheilanthescrenata, Woodsiacrenatavar.pallidipes, Woodsiaincisa, Woodsiamontevidensisvar.fuscipes and the second step lectotypification for Dicksoniamontevidensis and Woodsiaperuviana, based on the analysis of their protologues and original herbarium material. All names are currently synonyms of Woodsiamontevidensis. Physematiumincisum (Gillies ex Hook. & Grev.) Kunze constitutes an illegitimate name and Physematiumcumingianum is considered as nomen inquirendum.A revision of the nomenclature of six South American taxa related to Woodsia (Polypodiidae: Woodsiaceae) is a genus comprising about 35-40 taxa of small and tufted ferns growing on or in the vicinity of cliffs and rocks (PageBreakin the Rocky Mountains of western North America (ca. 10 spp.) and the Himalayas in south Asia (ca. 19 spp.); absent from Australia, New Zealand, SE Asia, and the Pacific (WoodsiasubgenusPhysematium (Kaulf.) Hook. emend. X.C. Zhang & R. Wei Hieron., with a distribution ranging from Venezuela and Colombia to central Argentina and Southern Brazil (nd rocks . They ma Pacific . The Neo& R. Wei . South An Brazil .http://www.floraargentina.edu.ar) and the Flora of Brazil and conssee ICN) .Woodsia in alphabetical order by the names under Woodsia, as all of them are current synonyms of Woodsiamontevidensis (Spreng.) Hieron., following In this paper we have arranged the South American taxa related to Woodsiacrenata (Kunze) Hieron. Bot. Jahrb. Syst. 34(4): 440. 1904. \u2261 Cheilanthescrenata Kunze, Linnaea 9: 84. 1834. Type: Peru. \u201cPeruv.(ia) Rupestribus ad Huanuco Martio 1830 lectae\u201d E.F. Poeppig, s.n. .1. Cheilanthescrenata from Huanuco, Peru collected by Poeppig at B, BM, K, L, LE, MO, NY, OXF, P, PCR, US and W. We were able to find original material at W that agrees well with Kunze`s original description, which we here select as lectotype, in order to avoid the misapplication of the name.Since Kunze\u2019s own herbarium in Leipzig is destroyed, we looked for further original material of PageBreakWoodsiacrenata var. pallidipes Hieron., Bot. Jahrb. Syst. 34(4): 440. 1904. Type: Colombia. \u201cAd muros et rupes prope Purac\u00e9\u201d, 2680-2800 m, 1 Feb 1884, F.C. Lehmann 3478. Lectotype (designated here): B [B-200170834!]; isolectotypes: B [B-200170833!], K [K-000632733!], US [US-00066996!].2. Woodsiacrenatavar.pallidipes, he cited four collections, three from Colombia and two from Bolivia. Bolivia: \u201csine loco, 1863\u201d, Mandon 19 B and Mandon 35 B . Colombia: \u201cad muros urbis Pasto\u201d, 2500 m, 11 Feb 1881, F.C. Lehmann 656 B [B-20170836!], \u201cad muros et rupes prope Purace\u201d, 2680-2800 m., 1 Feb 1884, F.C. Lehmann 3478 B , K [K-000632733!], US [US-00066996!], \u201cad muros et rupes prope Yermal, in provincia Antioquia\u201d, 1800-2400 m, Nov 1891, F.C. Lehmann 7411 B [B-20170835!], K [K-000632732!]. We selected a specimen from the F.C. Lehmann 3478 collection as lectotype because it corresponds with all characters used to describe the variety, furthermore the B specimen has a handwritten label by Hieronymus with the inscription \u201cWoodsiacrenatavar.pallidipes Hieron.\u201d and there are duplicates in three herbaria.When Woodsiaincisa Gillies ex Hook. & Grev., Icon. Filic. 2. t. 191. 1831 \u2261 Physematiumincisum (Gillies ex Hook. & Grev.) C. Presl, Tent.: 66. 1836. Type: Argentina. Mendoza: near San Luis, J. Gillies s.n. Lectotype (designated here): BM [BM-000937851!]; isolectotypes BM [BM-000937850!]; K [K-000229420!].3. BM consists of four fronds with two different barcodes on the same sheet: BM [BM-000937850 and BM-000937851], both with separate labels with the same information. We selected the material affiliated with BM [BM-000937851] as lectotype because it is more complete.The type material at J. Gillies 8 housed at K [K-000229420!] is not part of the original material because it was collected at \u201cSierras de Tandil\u201d, located in Buenos Aires province, Argentina, far away from the type locality.The specimen Physematiumincisum (Gillies ex Hook. & Grev.) Kunze (The combination .) Kunze is an ilWoodsiamontevidensis (Spreng.) Hieron., Bot. Jahrb. Syst. 22: 363. 1896. \u2261 Dicksoniamontevidensis Spreng., Syst. Veg. 4(1): 122. 1827. Type: Uruguay. (\u201cBrasilia\u201d) [Montevideo], Pan d\u2019A\u00e7ucar, F. Sellow d 517. Lectotype (first step designated by Tryon & Stolze [1991: 94]), second step (designated here): B [B-200094654!]; isolectotype B [B-200120343!].4. Sello\u201d. There are seven specimens of Sellow from Montevideo, five of them are kept in B, one in BM and another in K. Woodsiamontevidensis with a specimen at B. From all specimens deposited in B, two of them are numbered Sellow d 517 B [B-200094654! and B-200120343!] from Montevideo, as well quoted by Hieronymus when he made the combination under Woodsia \u201d on a third: \u201cPan d\u2019A\u00e7ucar\u201d, and on the fourth: \u201cd.517\u201d. The specimen B [B-200120343!] is considered isolectotype.The protologue only expresses \u201cMonte Video. Woodsia . The speBM [BM-000937849!], although probably being original material, are preferably excluded from lectotypification because the data of the label are not complete.The remaining specimens: B [B-200170837a], Montevideo, ex reliquiis Sellowianis, s.n., ded. Humboldt 1836, ex herb. Kunth, [the two fronds on the left], B [B-200170837b], Montevideo, Pan d\u2019 A\u00e7ucar, ex reliquiis Sellowianis, s.n., ded. Humboldt 1836 [the two fronds on the right], B [B-200120342 and B-200120344] bear the only annotation \u201cBrasilia\u201d without specific locality : B [B-200171577!]; isolectotypes: B , CORD!.5. fuscipes, he mentioned five collections in the protologue. Two collections from Bolivia: Illimani between Pongo and Apachate. alt.: 4350 m, 24 March 1873, collected by A. St\u00fcbel 1239 (B [B-200171573!]) and La Paz, Murillo, Zongo (\u201cprope Songo\u201d), Nov 1890, collected by M. Bang 878 . From Argentina, three additional collections were considered by Hieronymus as belonging to this variety: F. Schickendantz 68 , F. Schickendantz 360 (B [B-200171576!]), and P.G. Lorentz & G.H.E.W. Hieronymus 138 . Specimens of all five collections are present at B. In order to avoid any ambiguity regarding the application of the name, the specimen Lorentz & Hieronymus 138 (B [B-200171577!]) is selected as lectotype, while the three duplicates are regarded as isolectotypes in accordance to Art. 9.12 of the Code Trevis., Nuovo Giorn. Bot. Ital.7: 160. 1875. Type: Peru. \u201cHuamantanga, shady places\u201d, 1834-1835, A. Mathews 602. Lectotype (first step designated by Tryon & Stolze (1991: 94), second step (designated here): K [K-000632731!]; isolectotypes B , BM [BM-000937848 digital image!], GH [GH-00022287 digital image!], and K [K-000632730 digital image!].6. Woodsiaperuviana with a specimen at K as holotype, but K holds two sheets of Mathews 602 [K-000632730 and K-000632731], PageBreakthe last one is here designated as lectotype because the material is more complete, has a handwritten annotation \u201cPeru, Mathews\u201d and \u201cWoodsiaperuviana Hook. Spec. Fil. Tab. XXI\u201d on the sheet, and the label contains the locality data.A. Mathews s.n. (US [US-00067001!]), according with Taylor\u2019s annotation in the label of the specimen, could probably be part of the type collection, but we prefer to exclude it of lectotypification because the locality is not clear (only \u201cPeru\u201d is written in the label) and it is not originally numbered by Mathews.The specimen Woodsiacumingiana (Kunze) Hook., Sp. Fil. [W. J. Hooker] 1: 61. 1844. \u2261 Physematiumcumingianum Kunze, Analecta Pteridogr.: 43. 1837. Type: \u201cHabitat probabiliter in Chile, misit H. Cuming\u201d .LZ, was destroyed. As BM; however, no syntypes were found in this herbarium, nor in the Herbarium Hookerianum (K). Additionally, no material of this species from Chile was in B, BR, BM, E, GH, L, LE, OXF, P, W and Z, where duplicates of H. Cuming are deposited. Also, as consigned by Hooker (1844), most probably the type locality is mistaken, because he had the opportunity to revise the collections of Cuming immediately after his return and he was not able not find any specimen gathered by Cuming from either Chile or Peru. As the protologue expresses, the species is characterized by last segments oblong rounded, glanduloso-dentate decurrent, sori solitary upon the teeth, involucres glabrous, rachis and stipe subglabrous purple. With such description, the species is hardly to differenciate from many species of Woodsia, hence, the name is considered here as nomen inquirendum.The original material of this species, deposited in"} +{"text": "Scientific Reports5: Article number: 1262910.1038/srep12629; Published online: 07302015; Updated: 04292016The original version of this Article contained errors in the spelling of the authors Federico Vita, Cosimo Taiti, Antonio Pompeiano, Nadia Bazihizina, Valentina Lucarotti, Stefano Mancuso and Amedeo Alpi which were incorrectly given as Vita Federico, Taiti Cosimo, Pompeiano Antonio, Bazihizina Nadia, Lucarotti Valentina, Mancuso Stefano & Alpi Amedeo respectively. The Author Contributions Statement,V.F., A.A. and L.V. designed the research. V.F., T.C. and P.A. performed the experiments and analysed the data. V.F., A.A., M.S. and B.N. organized and drafted the paper with all authors contributing to the discussion of the data and to the writing.now reads:F.V., A.A. and V.L. designed the research. F.V., C.T. and A.P. performed the experiments and analysed the data. F.V., A.A., S.M. and N.B. organized and drafted the paper with all authors contributing to the discussion of the data and to the writing.In addition, the \u2018How to cite this article\u2019 section quoted an incorrect abbreviation for Federico Vita.These errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "During 2011\u20132012, an estimated 26.4% of U.S. adult males and 9.0% of females aged \u226520 years had low levels of HDL cholesterol . In all age groups, a higher percentage of men had low levels of HDL cholesterol than women. A higher percentage of men aged 40\u201359 years had low levels of HDL cholesterol than men aged \u226560 years.Source: Carroll MD, Kit BK, Lacher DA, Yoon SS. Total and high-density lipoprotein cholesterol in adults: National Health and Nutrition Examination Survey, 2011\u20132012. NCHS data brief no. 132. Hyattsville, MD: US Department of Health and Human Services, CDC; 2013. Available at http://www.cdc.gov/nchs/data/databriefs/db132.htm.Reported by: Margaret D. Carroll, MSPH, mdc3@cdc.gov, 301-458-4136; Steven M. Frenk, PhD."} +{"text": "Elephantomyia Osten Sacken (Diptera: Limoniidae) from Baltic amber (Eocene) is presented. Four species\u2014E. baltica Alexander, E. brevipalpa Loew, E. longirostris Loew, and E. pulchella Loew\u2014are redescribed and documented with photographs and drawings. In addition, two new species of the genus are described: Elephantomyia bozenae sp. nov., and Elephantomyia irinae sp. nov. All these fossil species are placed within the subgenus Elephantomyia. A key to the extinct species of Elephantomyia is provided, and the genus\u2019 ecological pattern and evolutionary aspects are discussed.A revision of the genus Elephantomyia . Th. ThElephntomyia) , occur mtomyina) , and E. ntomyia) . A similtomyina) . In the omyodes) is the mElephantomyia are known from amber inclusions, mainly from Eocene Baltic amber, but none were assigned to a subgenus. Four species of Elephantomyia are known from the Baltic amber: E. baltica .The electronic edition of this article conforms to the requirements of the amended International Code of Zoological Nomenclature, and hence the new names contained herein are available under that Code from the electronic edition of this article. This published work and the nomenclatural acts it contains have been registered in ZooBank, the online registration system for the ICZN. The ZooBank LSIDs (Life Science Identifiers) can be resolved and the associated information viewed through any standard web browser by appending the LSID to the prefix \u201cOrder: Diptera Linnaeus, 1758Family: Limoniidae Speiser, 1909Subfamily: Limoniinae Speiser, 1909Type species. Limnobiorhynchus canadensis : Evenhuis, p. 69.1994 Material examined. Holotype: No. 282 , Coll. University of G\u00f6ttingen (GMUG).E. (E.) baltica clearly differs from the other Baltic amber species of the genus Elephantomyia in its relatively short Rs vein. The length of vein Rs is only slightly longer than twice the length of the basal section of R5, in other species of this genus, the length of Rs is at least three times that of the basal section of R5. E. (E.) baltica also differs distinctly in the ratio between the wing, rostrum, and abdomen lengths: in E. (E.) baltica, the wing is as long as the rostrum, whereas in other species, the wing is distinctly longer than the rostrum. In E. (E.) baltica, the rostrum is longer than abdomen, whereas in E. (E.) brevipalpa, E. (E.) irinae sp. nov., and E. (E.) pulchella, the rostrum is shorter than, or as long as, the abdomen. Additionally, vein Rs in E. (E.) baltica is shorter than R2+3+4, in contrast to E. (E.) brevipalpa, where Rs is as long as or longer than R2+3+4. Moreover, E. (E.) baltica has an elongate palpus, much like the other Baltic amber species of the genus Elephantomyia, whereas the palpus in E. (E.) brevipalpa is very short, being less than half the length of the rostrum\u2019s glossal lobes. In E. (E.) baltica, cross-vein m-cu is situated just after the fork of Mb into M1+2 and M3+4, whereas in E. (E.) pulchella, m-cu is situated at exactly half the length of the d-cell.Body: brown, 9.5 mm long (without rostrum).Head: rostrum elongate, 8.5 mm long, as long as the wing, longer than abdomen . antenna5, shorter than the length of R2+3+4; R1 ending approximately two-fifths length of R2+3+4; r-r (R2) atrophied; M3 one and half times longer than d-cell; cross-vein m-cu before d-cell mid-length, just after of fork of Mb; A1 and A2 almost straight.Wing : 8.5 mm Leg: tibial spurs not visible.Hypopygium: not clearly visible.Ovipositor: only male specimens known.Remarks. The specimen is well preserved, but the number of segments of antenna is probably 14, but the flagellomeres are very crowded and the boundaries between individual flagellomeres is not clear.Material examined. Holotype: No. MP/3338 , Coll. Institute of Systematic and Evolution of Animals, Polish Academy of Sciences (ISEA PAS).Etymology. The specific name is dedicated to the eminent biologist Bo\u017cena Szala, MSc.E. (E.) bozenae sp. nov. is characterized by its elongate and narrow d-cell, which is approximately twice as long as wide; in E. (E.) baltica, E. (E.) irinae sp. nov., E. (E.) longirostris, and E. (E.) pulchela, the d-cell is shorter, being approximately 1.5 times longer than wide. In E. (E.) bozenae sp. nov., vein M3 is almost the same length as the d-cell, whereas M3 is longer than the d-cell in E. (E.) baltica, E. (E.) irinae sp. nov., E. (E.) longirostris, and E. (E.) pulchella sp. nov. Moreover, E. (E.) bozenae sp. nov. differs from other Baltic amber Elephantomyia species in the ratio of wing, rostrum, and abdomen lengths. In E. (E.) bozenae sp. nov., the rostrum is shorter than the wing, being slightly longer than half wing length, and longer than the abdomen. In contrast to E. (E.) pulchella, where m-cu is situated at exactly half of d-cell length, in E. (E.) bozenae sp. nov., m-cu is just before of half d-cell length. In E. (E.) bozenae sp. nov., Rs length is at least three times that of the basal section of R5, whereas in E. (E.) baltica the wing is as long as the rostrum, vein Rs is relatively short, and the length of vein Rs is only about twice the length of the basal section of R5. In E. (E.) bozenae sp. nov., Rs is shorter than R2+3+4, which contrasts to E. (E.) brevipalpa, where Rs is as long as R2+3+4 or longer. Moreover, the palpus in E. (E.) bozenae sp. nov. is elongate, unlike E. (E.) brevipalpa, where the palpus is very short, being shorter than half the length of the rostrum\u2019s glossal lobes.Body: brown, distal part of abdomen darker than rest of body, body 3.16 mm long (without rostrum).Head: rostrum elongate, 2.14 mm long, shorter than wing, ending just after half wing length, rostrum longer than abdomen . Antenna5, shorter than length of R2+3+4; R1 ending approximately half length of R2+3+4; r-r (R2) atrophied; M3 almost equal to d-cell length; cross-vein m-cu just before of d-cell mid-length; A1 almost straight, A2 slightly waved.Wing Figs. , 3A: 3.5Leg: tibial spurs not visible.Elephantomyia species, approximately twice as long as wide, with elongate, narrow, lobe-shaped interbase; outer gonostylus narrow, distinctly bifid at end, distal part curved externally; inner gonostylus slightly widened, strongly narrowed in apical part; directed into hypopygium.Hypopygium Figs. , 3C: 0.3Ovipositor: only male specimens known.Toxorhina brevipalpa Loew, p. 37. (nomen nudum).1850 Toxorhina brevipalpa Loew, p. 400.*. 1851 Limnobiorhynchus [brevipalpa] Osten Sacken, p. 221.1860 (1859) Elephantomyia [brevipalpa]: Osten Sacken, p. 106.1869 Elephantomyia brevipalpa Osten Sacken [sic!] (Toxorhina): Scudder, p. 180.1894 Elephantomyia brevipalpa : Meunier, p. 366.1906 Toxorhina brevipalpa Handlirsch, p. 991.1907 Elephantomyia brevipalpa : Alexander, p. 90.1931 Elephantomyia brevipalpa Evenhuis, p. 69.1994 Material examined. Holotype: No. MB.J. 337 , Coll. Berendt (NHMB); No. MP/3323 , Institute of Systematic and Evolution of Animals, Polish Academy of Sciences (ISEA PAS); No. 161 , Coll. Kutscher, University of G\u00f6ttingen (GMUG).E. (E.) brevipalpa differs distinctly from other Baltic amber species of this genus in the characteristic morphology of its palpus. In E. (E.) brevipalpa, the palpus is very short, being less than half the length of the rostrum\u2019s glossal lobes, whereas in other species, the palpus is relatively long. E. (E.) brevipalpa also differ from the other species redescribed and described here in the ratio between wing, rostrum, and abdomen lengths. In E. (E.) brevipalpa, the rostrum is shorter than the wing, being only slightly longer than half wing length, and shorter than abdomen. Moreover, in E. (E.) brevipalpa, vein Rs is as long as, or longer than, vein R2+3+4, in contrast to other species of this genus where Rs is distinctly shorter than R2+3+4. In E. (E.) brevipalpa Rs is more than three times the basal section of R5; in comparison, E. (E.) baltica has a relatively short Rs, only about twice the length of the basal section of R5. Cross-vein m-cu in E. (E.) brevipalpa is situated just after the fork of Mb into M1+2 and M3+4, whereas in E. (E.) pulchella, vein m-cu is half d-cell length. In E. (E.) brevipalpa, the d-cell is comparatively short and wide, being approximately one and half longer than wide, unlike E. (E.) bozenae sp. nov., where the d-cell is elongate and narrow, twice as long as wide. Moreover, vein M3 in E. (E.) brevipalpa is approximately one and half times longer than the d-cell, whereas in E. (E.) bozenae sp. nov., M3 is almost the same length as the d-cell.Body: brown, 5.1 mm long (without rostrum) .Head: rostrum elongate, 2.86 mm long , 2.86 mm long , shorter than wing, ending just longer than half wing length, longer than abdomen Figs. , 5A. Ant5 basal section, almost as long as, or longer than, R2+3+4; R1 short, ending approximately one-third length of R2+3+4; pterostigma base just after of Sc tip and before the bifurcation of Rs into R1, R2+3+4, and R5 ; r-r (R2) atrophied; M3 approximately one and half times longer than d-cell; cross-vein m-cu just before d-cell mid-length; A1 almost straight, A2 slightly waved.Wing Figs. , 5A, E: Leg: tibial spurs presented.Hypopygium Figs. , 5D: 0.4Ovipositor : 1.09 mmRemarks. In contrast to other Baltic amber species of Elephantomyia, the pterostigma base in E. brevipalpa is distinctly shifted towards the base of wing, being just distal to the tip of Sc and proximal of the bifurcation of Rs into R1, R2+3+4, and R5 . Additional material: No. MP/3330 , MP/3331 , No. MP/3337 , Coll. Institute of Systematic and Evolution of Animals, Polish Academy of Sciences (ISEA PAS); No. 250 , Coll. K\u00fcnow, University of G\u00f6ttingen (GMUG).Etymology. The specific name is dedicated to the eminent palaeoentomologist Dr. Irina D. Sukatsheva.E. (E.) irinae sp. nov. differs from E. (E.) longirostris, E. (E.) pulchella, E. (E.) bozenae sp. nov., and E. (E.) baltica in the ratio of rostrum and wing lengths. In E. (E.) irinae sp. nov., the rostrum is distinctly shorter than wing, ending just after half wing length; in E (E.) baltica, the rostrum is as long as the wing, whereas in. E. (E.) longirostris, the wing is only one-fifth longer than the rostrum, and in E. (E.) pulchella the wing is one-third longer than the rostrum. In contrast to E. bozenae sp. nov., where the rostrum is longer than the abdomen, the rostrum in E. (E.) irinae sp. nov. is distinctly shorter than the abdomen. From E. (E.) brevipalpa, E. (E.) irinae sp. nov. differs in the length of palpus: where in E. irinae (E.) sp. nov. the palpus is elongate, in E. (E.) brevipalpa the palpus is very short, less than half the length of the rostrum\u2019s glossal lobes. Moreover, in E. (E.) irinae sp. nov., the length of Rs is at least three times that of the basal section of R5, whereas in E. (E.) baltica, Rs is only about twice the length of the basal section of R5. Vein Rs in E. (E.) irinae sp. nov. is shorter than R2+3+4, in contrast to E. (E.) brevipalpa, where it is as long as, or longer than, R2+3+4. Cross-vein m-cu in E. (E.) irinae sp. nov. is situated after the fork of Mb into M1+2 and M3+4, but before half d-cell length; this is different from E. (E.) pulchella, where vein m-cu is situated at half d-cell length. In E. (E.) irinae sp. nov., the d-cell is rather short and wide, being one and half times as long as wide, whereas in E. (E.) bozenae sp. nov., the d-cell is elongate and narrow, and twice as long as wide. Moreover, vein M3 in E. (E.) irinae sp. nov. is approximately one and half times longer than the d-cell, but in E. (E.) bozenae sp. nov., M3 is almost the same length as the d-cell.Body: dark, 9.5 mm long (without rostrum).Head: rostrum not very elongate, 2.41\u20132.82 mm long, only slightly longer than half wing length, shorter than abdomen . Antenna5 basal section, shorter than half length of R2+3+4; R1 ending approximately half length of R2+3+4; r-r (R2) atrophied; M3 approximately one and half longer than d-cell; cross-vein m-cu before d-cell mid-length, about one-fourth its length beyond fork of Mb; A1 and A2 almost straight.Wing Figs. , 8A, C: Leg: tibial spurs invisible.Hypopygium Figs. , 8B: 0.5Ovipositor: only male specimens known.Toxorhina longirostris Loew, p. 37 (nomen nudum).1850 Toxorhina longirostris Loew, p. 400.* 1851 Limnobiorhynchus [longirostris] Osten Sacken, p. 221.1860 (1859) Elephantomyia [longirostris] Osten Sacken, p. 106.1869 Elephantomyia longirostris Osten Sacken [sic!] (Toxorhina): Scudder: 180.1894 Elephantomyia longirostris : Meunier, pp. 365\u2013366.1906 Toxorhina longirostris Handlirsch, p. 991.1907 Elephantomyia longiostris : Alexander, p. 90.p. 1931 Elephantomyia longirostris Evenhuis, p. 69.1994 Material examined. Holotype: No. MB.J. 338 , Coll. Berendt (NHMB); No. 1089\u20136 , Coll. Ch. and H. Hoffeins; No. MP/1627 ; No. MP/3319 , No. MP/3322 , No. MP/3325 , No. MP/3328 , No. MP/3329 , No. MP/3333 , No. MP/3334 , Coll. Institute of Systematic and Evolution of Animals, Polish Academy of Sciences (ISEA PAS); No. 19946 , Coll. Museum of the Earth, Polish Academy of Sciences, Warsaw (MEPAS).E. (E.) longirostris differs from other Baltic amber species of this genus in its very elongate rostrum, which is longer than the abdomen, and almost as long as the body length, being only one-fifth shorter than wing length. In E. (E.) baltica, the rostrum is longer than the abdomen and is equal in length to the wing; in E. (E.) bozenae sp. nov. and E. (E.) brevipalpa, the rostrum is longer than the abdomen but ends only slightly distal of half wing length; in E. (E.) irinae sp. nov., the rostrum is shorter than the abdomen; and in E. (E.) pulchella the rostrum is one-third shorter than the wing, whereas in E. (E.) irinae sp. nov., the rostrum ends just distal of half wing length. Although in E. (E.) baltica the length of vein Rs is only about twice the length of the basal section of R5, in E. (E.) longirostris, Rs is at least three times the length of the basal section of R5. In E. (E.) longirostris sp. nov. vein Rs is shorter than R2+3+4, which contrasts to E. (E.) brevipalpa, where Rs is as long as, or longer than, R2+3+4. Moreover, E. (E.) longirostris differs from E. (E.) brevipalpa in palpus morphology: in E. (E.) longirostris, the palpus is elongate, whereas in E. (E.) brevipalpa the palpus is very short, being shorter than half the length of the rostrum\u2019s glossal lobes. Cross-vein m-cu in E. (E.) longirostris is positioned shortly after of the fork of Mb into M1+2 and M3+4, different from in E. (E.) pulchella, where m-cu is at exactly half d-cell length. In E. (E.) longirostris, the d-cell is comparatively short and wide, being approximately one and half times longer than wide, whereas in E. (E.) bozenae sp. nov., the d-cell is elongate and narrow, being twice as long as wide. Moreover, vein M3 in E. (E.) longirostris is one and half times longer than the d-cell, but in E. (E.) bozenae sp. nov. M3 is almost the same length as the d-cell.Body: brown with elongate rostrum, 3.00\u20134.91 mm long (without rostrum).Head: rostrum 2.66\u20134.20 mm long, approximately equal to body length, longer than abdomen length, only one-fifth shorter than wing . Antenna5, shorter than length of R2+3+4; R1 ending at approximately half length of R2+3+4; r-r (R2) atrophied; M3 approximately 1.5 times longer than d-cell length; cross-vein m-cu situated just after fork of Mb into M1+2 and M3+4; A1 almost straight, A2 slightly waved.Wing Figs. , 10B, D:Leg: tibial spurs present.Hypopygium Figs. , 10C: 0.Ovipositor: only male specimens known.Remarks. The specimens No. K5100Z4080 (GMUG) and No. 87 (GMUG), reported as E. longirostris by Alexander Osten Sacken, p. 221.1860 (1859) Elephantomyia [pulchella] Osten Sacken, p. 106.1869 Elephantomyia pulchella Osten Sacken [sic!] (Toxorhina): Scudder, p. 180.1894 Elephantomyia pulchella : Meunier, p. 365.1906 Toxorhina pulchella Handlirsch, p. 991.1907 Elephantomyia pulchella : Alexander, p. 91.1931 Elephantomyia pulchella Loew, 1851: Evenhuis, p. 69.1994 Material examined. Holotype: No. MB.J. 336 , Coll. Berendt (NHMB); No. 1195\u20135 , Coll. Ch. and H. W. Hoffeins; No. MP/3336 Institute of Systematic and Evolution of Animals, Polish Academy of Sciences (ISEA PAS).E. (E.) pulchella differs from all other species of the genus Elephantomyia known from the Baltic amber in the position of cross-vein m-cu, which in this species is located at exactly half d-cell length, whereas in other species of this genus, this cross-vein is situated just after the fork of Mb into M1+2 and M3+4 or just before the d-cell mid-length. E. (E.) pulchella also differs from the other fossil Elephantomyia species in the ratio of wing, rostrum, and abdomen length. In E. (E.) pulchella, the rostrum is one-third shorter than the wing, but is the same length, or slightly longer than, the abdomen. Moreover, in E. (E.) pulchella the length of Rs is at least three times that of the basal section of R5, whereas in E. (E.) baltica, vein Rs is relatively short, being only about twice the length of the basal section of R5. Additionally, Rs in E. (E.) puchella is shorter than R2+3+4, in contrast to E. (E.) brevipalpa where Rs is as long as, or longer than, R2+3+4. Moreover, the palpus is elongate in E. (E.) pulchella, much like other fossil species of the genus Elephantomyia, which differs from E. (E.) brevipalpa, where the palpus is very short, being less than half the length of the rostrum\u2019s glossal lobes. In E. (E.) pulchella, the d-cell is comparatively short and wide, being approximately one and half times longer than wide; in E. (E.) bozenae sp. nov., the d-cell is elongate and narrow at twice as long as wide. Moreover, vein M3 in E. (E.) pulchella is approximately one and half times longer than the d-cell, whereas M3 is almost the same length as d-cell in E. (E.) bozenae sp. nov.Body: brown, 3.42\u20133.63 mm long (without rostrum).Head Figs. , 13B: he5, shorter than length of R2+3+4; R1 ending at approximately half length of R2+3+4; r-r (R2) atrophied; M3 approximately one and half times longer than d-cell; cross-vein m-cu at exactly half d-cell length; A1 almost straight, A2 slightly waved.Wing Figs. : 3.8\u20134.5Leg: tibial spurs present.Hypopygium Figs. , 13C: 0.Ovipositor: only male specimens known.Elephantomyia appeared in the Eocene, ~100 million years after the earliest representatives of the closely related genus Helius supernumeraria in inElephaHelius ewa . T. THeliusne-flies . TherefoTA-grade which belization . These clization , 31], [, [Heliuslization . However"} +{"text": "SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response. The 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are widely prescribed and are highly effective in the management and prevention of cardiovascular disease. Statin therapy results in a lowering of low-density lipoprotein cholesterol (LDL-C) levels by up to 55%45ABCG2 (rs2199936), LPA (rs10455872) and APOE (rs7412), that were associated with percentage LDL-C reduction following rosuvastatin therapyLPA (rs10455872) and APOE (rs445925 and rs4420638) were associated with LDL-C response to atorvastatin treatmentCLMN (rs8014194) that is associated with the magnitude of statin-induced reduction in plasma cholesterol6A small number of genome-wide association studies (GWAS) have previously identified loci associated with statin response on a genome-wide level. A GWAS in the JUPITER trial identified three genetic loci, rs1045582 and APOBCG2 rs219936, LPAAPOE and LPA. To determine whether additional loci may influence LDL-C response to statins, we formed the Genomic Investigation of Statin Therapy (GIST) consortium and conducted a pharmacogenetic meta-analysis using GWAS data sets from randomized controlled trials (RCTs) and observational studies. We identify two loci not previously identified in GWAS, SORT1/CELSR2/PSRC1 and SLCO1B1. In addition, we confirm the associations within the APOE and LPA genes. These findings will extend the knowledge of the pharmacogenetic architecture of statin response.On the basis of these studies, as well as previous candidate gene studies4n=8,421 statin recipients) and 10 observational studies that participated in the first stage for association with LDL-C response to statin treatment =0.098, \u03b2=\u22120.043, s.e.=0.005, P=1.58 \u00d7 10\u221218; LPA on chromosome 6 , although genotypes for this SNP were only available in two studies within the first stage .The first-stage meta-analysis identified three loci, including 13 SNPs, that attained genome-wide significance , were selected for additional genotyping in the Scandinavian ASCOT participants (see Methods). None of these six SNPs reached genome-wide significance after this additional genotyping from two of the trials in GIST, CAP and PRINCE showed a small and nonsignificant association with change in very small LDL (SLCO1B1), the borderline significant association with smaller magnitude of LDL-C reduction showed a trend for preferential association with larger versus smaller LDL subfractions. The lack of association of rs10455872 (LPA) with changes in LDL subfractions is consistent with evidence discussed below that this locus affects levels of lipoprotein(a) (Lp(a)) and not LDL particles. Using generalized estimating equations, we tested the association of log change in each of the LDL subfractions with interactions of the four SNPs. For very small LDL, the association with the rs646776 minor allele was significantly different from that of the other minor alleles (P=0.03 after adjustment for multiple testing).To extend our results for the novel GWAS finding mall LDL . In contmall LDL . For theP<1 \u00d7 10\u22128), which were available in the CARDS data set. Correcting our effect size estimate further and modelling measurement noise at baseline reduced the apparent effect only slightly for all the markers, suggesting that there is little effect of measurement noise. Next, within the JUPITER trial, additional analyses were performed to determine whether there was an interaction between LDL-C change and statin or placebo allocation. P values for interaction for SNPs at the four genome-wide significant loci in the GIST meta-analysis, also suggesting that genetic effects on baseline LDL-C as manifested in the placebo group contribute at most only in part to genetic effects on LDL-C response in the statin group.To demonstrate that our findings for LDL-C response to statin treatment are unlikely to be explained through associations with baseline LDL-C levels, we performed a number of additional analyses (see Methods). First, To investigate whether there were multiple SNPs within any gene and multiple loci associated with differential LDL-C lowering to statin therapy, we performed a conditional analysis across the genome using the summary statistics of the combined meta-analysis. The results of the Genome-Wide Conditional Analysis with LDL-C response-associated variants, resulting in a list of 185 candidate gene loci, defined by 2,681 SNPs showed convincing evidence of statin responsiveness on the basis of greater than twofold differential expression in response to statin treatment. Eight genes showed suggestive evidence . A total of 420 expression quantitative trait loci (eQTL) associations were identified across a wide range of tissues , which c681 SNPs . To idenAPOE/TOMM40/PVRL2 and SORT1/CELSR2/PSRC2.Finally, involvement in statin response was investigated at a pathway level using GeneGo Metacore 8Nine SNPs in the 412 ref. 14, was aLPA were significantly associated with LDL-C response to statins. The minor G allele of the lead SNP rs10455872 was associated with smaller LDL-C reduction than the major allele. This result was similar to the previous GWAS findings for this SNP in the JUPITER trial and the combined ASCOT and CARDS study786LPA variant are characterized by higher Lp(a) levels and a larger proportion of their measured LDL-C resides in Lp(a) particles8Three independent SNPs at SORT1/CELSR2/PSRC1 (rs646776 and rs12740374) on chromosome 1p were associated with an enhanced statin LDL-C response. A similar association was previously observed in a large candidate gene study in HPSSORT1, CELSR2 and PSRC1 with rs4149056, which represents the Val174Ala substitution resulting in complete loss of function. In the HPS trial, which used simvastatin, this candidate gene SNP was associated with a 1% lower LDL-C reduction per alleleSLCO1B1 showed the strongest associationSLCO1B1 variant had a 16.9 times higher risk for myopathy compared with non-carriers. This might have led to a decrease in study medication adherence, and consequently a decreased effect on LDL-C in carriers of this SNP. In addition, previous analysis in the GoDARTS study showed that the effect of the SLCO1B1 gene on statin efficacy was abolished after removal of individuals who showed signs of intoleranceThe APOE gene region and two loci in the LPA gene region . These findings will require replication in independent, larger data sets. The significant SNPs in the GWCA analysis explained ~5% of the variation in LDL-C response to statin treatment. Whether this 5% is clinically relevant should be investigated by other studies. For example, it would be of interest to investigate whether this differential LDL-C lowering is also associated with differential event reduction by statin treatment.GWCA identified three independent loci in the e region . GWCA alSLCO1B1 variant on statin pharmacogenetics is known to be highly dependent on statin type and dose24SLCO1B1 gene was genome-wide significantly associated with LDL lowering, this highlights the thoroughness of our analytical approach, in which the analyses were correctly adjusted for the type and dose of statins used and 11 prospective, population-based studies. The initial analysis (first stage) was performed in 8,421 statin-treated subjects from 6 RCTs and 10,175 statin-treated subjects from 10 observational studies . Further investigation (second stage) was performed in 21,975 statin-treated subjects from two randomized trials (HPS and JUPITER) and one observational study (Rotterdam Study). Six SNPs were additionally genotyped in the Scandinavian participants of the ASCOT study. The details of the first- and second-stage studies can be found in the Response to statin treatment was studied in statin-treated subjects only and not in those treated with placebo. Subjects included in the observational studies\u2019 analysis should be treated with statins and have LDL-C measurements before and after start of statin treatment. Subjects of reported or suspected non-European ancestry were excluded. All participants gave written informed consent and the study was approved by all institutional ethics committees.The response to statin treatment was defined as the difference between the natural log-transformed on- and off-treatment LDL-C levels. The beta of the corresponding regression thus reflects the fraction of differential LDL lowering in carriers versus non-carriers of the SNP. For observational studies, the on-treatment LDL-C levels were taken into account for all kinds of prescribed statins, at any dosage, for any indication and for at least 4 weeks before measurement. Characteristics of on- and off-treatment LDL-C levels and statins used in each study are shown in Genotyping, quality control, data cleaning and imputation were performed independently in each study using different genetic platforms and software as outlined in Each study independently performed the GWAS on the difference between natural log-transformed on- and off-treatment LDL-C levels. To control for possible associations with off-treatment LDL-C levels, analyses were adjusted for the natural log-transformed off-treatment LDL-C level. An additive genetic model was assumed and tested using a linear regression model. For imputed SNPs, regression analysis was performed onto expected allele dosage. Analyses were additionally adjusted for age-, sex- and study-specific covariates . Analyses in the observational studies were, if available, additionally adjusted for the statin dose by the natural logarithm of the dose equivalent as defined in http://www.sph.umich.edu/csg/abecasis/Metal/index.html). A fixed effects, inverse variance weighted approach was used. Using an inverse variance weighted meta-analysis will give smaller weights to studies with large s.e.. To correct for possible population stratification, genomic control was performed by adjusting the within-study findings and the meta-analysis results for the genomic inflation factor.Centrally, within each study, SNPs with MAF <1% or imputation quality <0.3 were excluded from the analysis. QQ-plots were assessed for each study to identify between-study differences . The sofP values <5 \u00d7 10\u22124 in the first-stage meta-analysis were selected for further investigation in a second stage. A maximum of two SNPs per locus were selected, based on statistical significance, except for the APOE locus, for which all genome-wide significant associated SNPs were selected for validation. A total of 246 SNPs, within 158 independent loci, were selected for the second stage, which was performed in the JUPITER trial, HPS study and the Rotterdam Study, which all had GWAS data and response to statin treatment available. For 2 of the 246 SNPs, a proxy was used in the JUPITER trial, and 31 SNPs were not available, nor was a proxy SNP. HPS provided data on 151 directly genotyped SNPs from GWAS and IPLEX experiments, including 48 of the requested SNPs and 103 proxy SNPs (r2>0.8). Analysis in HPS was not adjusted for ln baseline LDL-C levels. In addition, the number of subjects with data varied from SNP-to-SNP and ranges from ~4,000 for variants with GWAS data to ~18,000 for some candidate genes. Results of the first and second stage were combined using fixed effects, inverse variance weighted meta-analysis and analysed by METAL. As a third stage, six SNPs with P values 5 \u00d7 10\u221280.8)) were reviewed for evidence of involvement in statin response at a pathway level using GeneGo Metacore ). A statin response network was constructed in two stages. First, all genes with a literature-reported involvement in statin response ) were identified using GeneGo MetaCore across four HapMap builds in European ancestry samples (CEU) using the SNAP tool ( http://www.broadinstitute.org/mpg/snap/). The primary index SNPs and LD proxies were searched against a collected database of expression SNP (eSNP) results, including the following tissues: fresh lymphocytes333435374142et al., unpublished), CD19+ B cells44Mycobacterium tuberculosis infection3343465254535349584943LDL-C-associated index SNPs 246 SNPs) were used to identify 1,443 LD proxy SNPs displaying complete LD ( SNPs werwww.broadinstitute.org/cmap) and contains more than 7,000 expression profiles representing 1,309 compounds used on five different cultured human cancer cell lines . We selected (prostate tumour-derived) PC3 cells as they showed the most responsiveness to statins at a genome-wide level. Four statins were included in our analysis, including pravastatin, atorvastatin, simvastatin and rosuvastatin. PC3 Instance reference files for each statin treatment were extracted data set is available at the Broad Institute ( r2>0.8) with associated variants were explored for impact on coding gene function using AnnovarGenes and variants across all LDL-C-associated loci were investigated for evidence of functional perturbation using a range of bioinformatics tools and databases. Variants showing LD J.W.J., D.J.S., B.M.B., I.F., N.S. and R.G.J.W.; (ASCOT) M.J.C., P.S., N.P., A.S., D.C.S. and E.O.; (CARDS) H.A.D., H.M.C., P.M.M., J.B., P.N.D., A.D. and G.H.; (PARC) X.L., Y.-D.I.C., J.I.R. and R.M.K.; (TNT) J.J.P.K.; (AGES) L.J.L., T.B.H. and V.G.; (ARIC) C.L.A., E.A.W., T.S., E.B. and C.M.B.; (BioVU) Q.F., W.-Q.W., R.A.W. and J.C.D.; N.S., K.R., T.L., J.I.R., B.M.P. and S.R.H.; (FHS) L.A.C. and V.R.; (GoDARTS) C.N.A.P. and H.M.C.; (HABC) Y.L.; (MESA) X.G., S.R.H., W.P. and J.I.R.; (Rotterdam Study) C.E.d.K., B.H.S., A.G.U., A.H. and F.R.; and (JUPITER) D.I.C., B.J.B., F.N. and P.M.R.Phenotype data acquisition of contributing studies by (PROSPER) J.W.J., D.J.S., B.M.B., I.F., A.J.M.d.C., N.S. and R.G.J.W.; (ASCOT) M.J.C., P.B.M., P.S., N.P., A.S., D.C.S., E.O. and S.S.H.; (CARDS) H.A.D., H.M.C., P.M.M., J.B., P.N.D., A.D. and G.H.; (PARC) X.L., Y.-D.I.C., J.I.R. and R.M.K.; (TNT) J.J.P.K.; (AGES) G.E.; (ARIC) C.M.B.; (BioVU) W.W.; K.L.W., J.C.B., A.M.A., N.L.S., B.M.P. and S.R.H.; (FHS) L.A.C., C.J.O., V.R.; (GoDARTS) C.N.A.P., L.A.D., K.Z., A.D., A.M. and H.M.C.; (HABC) D.M.H. and S.B.K.; (MESA) W.P. and J.I.R.; (Rotterdam Study) C.E.K., B.H.S., A.H. and O.H.F.; (JUPITER) D.I.C., F.G., J.G.M. and P.M.R.Genotype data acquisition of contributing studies by (PROSPER) S.T., J.W.J., A.J.M.C. and P.E.S.; (ASCOT) M.J.C., P.B.M., P.S., A.S. and S.S.H.; (CARDS) H.A.D., H.M.C., P.M.M., P.N.D., A.D. and G.H.; (PARC) Y.-D.I.C., J.I.R., D.A.N. and J.D.S.; (TNT) B.J.A., M.P.D., S.M.B., G.K.H. and J.-C.T.; (AGES) A.V.S.; (ARIC) E.B.; (BioVU) Q.F., J.C.D., C.T.L. and F.S.; G.L., J.C.B., K.D.T., J.I.R., K.R., T.L. and S.R.H.; (FHS) C.J.O.; (GoDARTS) C.N.A.P., K.Z., A.D., F.C., H.M.C., M.I.M., L.G., E.A. and WTCCC2; (HABC) Y.L.; (MESA) K.D.T. and J.I.R.; (Rotterdam Study) A.G.U. and F.R.; and (JUPITER) D.I.C., F.G., B.J.B., F.N. and P.M.R.Primary analysis from contributing studies by (PROSPER) I.P., S.T., A.J.M.C. and P.E.S.; (ASCOT) M.J.C., M.R.B. and H.R.W.; (CARDS) H.A.D., H.M.C. and P.M.M.; (PARC) X.L., Y.-D.I.C. and J.I.R.; (TNT) B.J.A., M.P.D., S.M.B., G.K.H. and J.-C.T.; (AGES) A.V.S.; (ARIC) C.L.A., E.A.W. and T.S.; (BioVU) Q.F., W.W., C.T.L. and F.S.; K.L.W. and G.L.; (FHS) L.A.C., P.G. and J.S.N.; (GoDARTS) C.N.A.P., L.A.D., K.Z. and H.M.C.; (HABC) D.S.E., J.M.S. and J.D.; (MESA) K.D.T., X.G., X.L. and J.I.R.; (Rotterdam Study) C.E.K. and B.H.S.; and (JUPITER) D.I.C., A.Y.C., F.G., J.G.M. and P.M.R.How to cite this article: Postmus, I. et al. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat. Commun. 5:5068 doi: 10.1038/ncomms6068 (2014).Supplementary Figures 1-4, Supplementary Tables 1-10, Supplementary Notes 1-3 and Supplementary ReferencesExpression Quantitative trait loci (eQTLs) linked to LDL-C associated SNPSFunctional characterization of all variants showing LD with with LDL-C associated SNPsCandidate loci defined by association and eQTLs identified in this studyGeneGo custom network of known statin interacting genes"} +{"text": "The first two authors, Keith K.W. Chan and Regina W.S. Sit, should be noted as contributing equally to this work."} +{"text": "There are errors in the current addresses for authors Uma. K. Aryal and Andrew R. S. Ross. The correct current address for Uma. K. Aryal is Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA. The correct current address for Andrew R. S. Ross is Fisheries and Oceans Canada, Institute of Ocean Sciences, Sidney, BC, V8L 4B2, Canada. The publisher apologizes for the errors."} +{"text": "Borrelia in Zhejiang Province, we performed a survey in nine sites. A total of 447 adult ticks of 11 species were captured and the dominant tick species were Haemaphysalis longicornis and Ixodes sinensis and the abundance of tick species in different areas varied significantly. Overall, 4.70% of the ticks were polymerase chain reaction (PCR) positive for Borrelia. The average PCR positive rates were 5.19% for H. longicornis, 3.45% for Amblyomma testudinarium, 1.06% for I. sinensis, 5.00% for Rhipicephalus (Boophilus) microplus, and 19.44% for Ixodes granulatus, respectively. No Borrelia DNA was detected in Rhiphicephalus haemaphysaloides, Haemaphysalis yeni, Dermacentor taiwanensis, Haemaphysalis hystricis, Hyalomna asiaticum, and Ixodes ovatus. The prevalence of Borrelia was significantly different among tick species and the prevalence in I. granulatus was significantly higher than that in other tick species. Of note, experimentally confirmed vectors for B. burgdorferi s.l. including I. sinensis and I. granulatus were found in Zhejiang Province. Two species of B. burgdorferi s.l. exist in Zhejiang Province of which 12 sequences were most similar to the sequence of Borrelia garinii and nine sequences were most similar to the sequence of Borrelia valaisiana or Borrelia yangtze sp. nov.To explore the tick distribution and prevalence of Borrelia burgdorferi s.l., was first identified from the hard tick Ixodes scapularis in the autumn of 1981.Borellia burgdorferi s.l. have been described: B. burgdorferi sensu stricto, B. garinii, B. afzelii, B. japonica, B. valaisiana, B. lusitaniae, B. andersonii, B. tanukii, B. turdi, B. bissettii, B. sinica, B. spielmanii, B. californiensis, B. carolinensis sp. nov., B. americana, B. bavariensis, B. finlandensis, B. kurtenbachii, and B. yangzte.13Ticks are important vectors for human and animal pathogens of viral, bacterial, and protozoan nature worldwide. Lyme disease is a tick-borne disease that is common in all temperate regions of the Northern Hemisphere and it is the most common tick-borne disease in the United States. Most infections occur during the months of May through August, when both the nymph ticks' activity and human outdoor activity are at their peak. The causative agent for Lyme disease, B. burgdorferi s.l. genotyping studies have been conducted.B. burgdorferi s.l. in serum of humans from different areas in Zhejiang Province.Borrelia are essential to describe and understand the risk of acquiring Borrelia infections. To explore the tick distribution and prevalence of Borrelia, we performed a survey in nine locations in Zhejiang Province in Eastern China.In China, the first case of Lyme disease was reported in Hailin county Heilongjiang province in 1987.Sus scrofa trapped by local hunters or sold at markets. The other ticks were collected from wild mammals including Erinaceus amurensis, Apodemus agrarius, Rattus niviventer, and Suncus murinus, which were trapped with mousetraps. Collections of tick samples were conducted during January 2010 to December 2011. Only adult ticks were collected and no questing ticks were collected. All ticks were identified to the species level by standard guides and were stored at \u221220\u00b0C before DNA extraction.The investigated sites included Daishan, Xinchang, Jindong, Tiantai, Xianju Yongjia, Wencheng, Taishun, and Anji and were randomly chosen based on their geographical and administrative locations . Some tiEach adult tick was subjected individually to DNA extraction. Ticks were washed using 70% ethanol once; they were then washed three times with sterile deionized water to decontaminate the surface. Individual ticks were placed into different sterilized mortars and crushed with corresponding sterile pestles with liquid nitrogen. The DNA was prepared from the crushed ticks using the QIAamp Tissue Kit according to the manufacturer's instructions.Borrelia infection through testing them individually by nested PCR amplification, which was performed using a MyCyclerThermal Cycler with the primers , 200 mM each dNTP, 1.25 U Taq polymerase, and 0.5 mM each respective primer. Nested PCR was performed using 1 uL of the primary PCR product as the template. The PCR products were run in a 1.5% agarose gel, stained with gold view, and visualized using UV light. To avoid cross-contamination, all steps were performed in separate rooms; mastermix was prepared under a laminar air flow bench. In each PCR, at least two negative controls contained mastermix and sterile water instead of DNA template.After electrophoresis, all positive DNA amplicons were purified using the Promega Wizard PCR Preps Kit and then cloned into the PGEM-T Easy vector system (Promega) following the manufacturer's protocol. The white recombinant clones were selected for sequencing. Bidirectional sequencing of positive PCR products were commercially conducted by Shanghai Sangon Biotechnology Co. .http://blast.ncbi.nlm.nih.gov/Blast.cgi).Our sequences were compared with published sequences using the Basic Local Alignment Tool (BLAST) program from the National Center for Biotechnology Information Website .Logistic regression analysis, \u03c7Haemaphysalis longicornis (47.43%) and Ixodes sinensis (21.03%) in Zhejiang Province. However, the abundance of tick species varied significantly in different areas. Haemaphysalis longicornis was dominant in Daishan (91.38%), Xinchang (80.00%), Taishun (76.67%), and Yongjia (94.29%); H. longicornis (21.43%), Rhiphicephalus haemaphysaloides (21.43%), and I. sinensis (22.86%) in Jindong; I. sinensis (100%) in Tiantai; H. longicornis (58.14%) and Rhipicephalus microplus (41.86%) in Xianju; Amblyomma testudinarium (23.96%) and I. sinensis (65.63%) in Anji; Ixodes granulatus (100%) in Wencheng , cattle (54.72%), and Sus scrofa (6.60%). Ixodes sinensis ticks were from sheep (63.83%) and cattle (36.17%). Ixodes granulatus ticks were from Apodemus agrarius (41.67%), Rattus niviventer (27.78%), and Suncus murinus (30.55%). Additionally, R. haemaphysaloides and A. testudinarium were all from domestic dogs, all B. microplus were from cattle, H. yeni, H. hystricis, and H. asiaticum from S. scrofa, D. taiwanensis and I. ovatus were from Eragrotis amurensis.A total of 447 adult ticks of 11 species were captured . The domWencheng . HaemaphH. longicornis, 3.45% (1 of 29) for A. testudinarium, 1.06% (1 of 94) for I. sinensis, 5.00% (1 of 20) for R. microplus, and 19.44% (7 of 36) for I. granulatus, respectively and the prevalence in I. granulatus was significantly higher than that in other species of ticks of the ticks were PCR positive. The average PCR-positive rates were 5.19% (11 of 212) for ectively . No Borr2 = 69.385, P = 0.000 < 0.05).The prevalences in Daishan, Xinchang, Jindong, Tiantai, Xianju, Anji, Wencheng, Taishun, and Yongjia were 0, 0, 2.86%, 6.67%, 23.26%, 1.04%, 23.33%, 0, and 0, respectively . The pre2 value in omnibus tests of model coefficients was determined as 28.835 (P = 0.000). Furthermore, the overall correct percentage was found to be 95.3%. Variables in the equation below included tick species and sampling site\u00d7host species and place of residence and the Wald values were determined to be 11.465 (P = 0.001) and 16.443 (P = 0.000). The equation wasAccording to results of logistic analysis, the \u03c7B. garinii , which were all B. garinii 5S-23S rRNA partial sequences detected from I. ricinus in Russia, Turkey, and Czech Republic, respectively. The sequences of samples 145, 168, 344, and 345 were identical to B. valaisiana 5S-23S rRNA partial sequence (GenBank accession no. HM100120), which was detected in I. granulatus ticks from Taiwan. Moreover, the sequences of samples 349, 350 were identical to another B. valaisiana 5S-23S rRNA partial sequence (GenBank accession no. HM100125), which was detected in I. granulatus ticks from Taiwan and the sequence of 354 had the highest sequence similarity (99%) to this sequence. The sequence of sample 348 was most similar (96%) to B. valaisiana 5S-23S rRNA partial sequence (GenBank accession no. JX888445), which was detected from human blood in Heilongjiang Province, China. The sequence of sample 360 was identical to B. yantze strain QSYSP3 5S-23S ribosomal RNA partial sequence detected in H. longicornis from southwestern China.As shown in B. garinii were detected in H. longicornis except for one sequence that was detected in A. testudinarium (KJ398184). The majority of sequences that were most similar to B. valaisiana were detected in I. granulatus except for two sequences, one sequence was from I. sinensis and the other was from B. microplus and the sequences that were most similar to B. valaisiana came from three additional areas . Moreover, H. longicornis and A. testudinarium ticks, Borreia sequences detected in them were most similar to B. garinii, were collected from cattle and dogs, respectively. Ixodes granulatus, I. sinensis, and B. microplus, Borrelia sequences detected in them were most similar to B. valaisiana, were collected from S. scrofa, cattle, A. agrarius, and R. niviventer.All sequences that were most similar to icroplus . The seqB. burgdorferi s.l. in ticks collected from different sites in Eastern China. A total of 11 species of ticks were found in nine areas of Eastern China. The distribution of tick species varied considerably in the different areas. This variability may have been caused by different hosts from which ticks were collected and different habitats in sampling sites. The dominant tick species of Zhejiang Province are H. longicornis and I. sinensis.Previous studies in China reported the prevalence and genetic characteristics of B. burgdorferi s.l. was found to be 4.70% among ticks as detected using nested PCR. Previous studies reported that Borrelia spp. were detected in 22 of 55 (40.00%) ticks,I. persulcatus ticks,I. granulatus ticks,Borrelia detection.In our study, the overall infection rate with I. granulatus and H. longicornis were higher than that in other species of ticks. The findings indicate that I. granulatus and H. longicornis may play roles as vector or carrier of Borrelia in Eastern China. However, we cannot exclude that other ticks might act as carriers for B. burgdorferi s.l. because of small sample sizes. Additionally, former studies have shown that I. granulatus ticks are vector of Borrelia, but H. longicornis only carry Borrelia and cannot transmit it.H. longicornis ticks are not the main vector of Borrelia, although they were dominant in Zhejiang Province. Similarly, I. sinensis ticks were experimentally confirmed vector and H. yeni ticks were confirmed as being incapable of serving as a vector for B. burgdorferi s.l. Other tick species collected in our study have unknown vector status (B. burgdorferi s.l. complex spirochetes, B. afzelii, B. bavariensis, B. garinii, B. spielmanii and B. burgdorferi sensu stricto are known to be pathogenic for humans, and B. valaisiana, and B. lusitaniae are considered potentially pathogenic.B. garinii and B. valaisiana or B. yangtze sp. nov. in ticks that were LD vectors indicate that transmission of LD via tick bite in Zhejiang Province is possible.Our data showed that the prevalences in r status . Of B. bB. burgdorferi s.l. in China shows that B. garinii was the main genotype in China and distributed mainly in northern China, B. afzelii was the second most frequently found species and distributed in both northern and southern China, and all B. valaisiana strains were isolated from southern China.B. burgdorferi s.l. might exist in Zhejiang Province of which 12 sequences were most similar to the sequence of B. garinii and the other sequences were most similar to the sequence of B. valaisiana or B. yangtze sp. nov. The reason might be that Zhejiang Province is located in east-central China. The sequences, which were found in our study, are similar to sequences that have been designated B. yangtze sp. nov. or B. valaisiana in different studies. To determine the proper species designation further studies are required using multilocus sequence typing.A report on distribution of B. garinii were detected in H. longicornis and the majority of sequences that were most similar to B. valaisiana or B. yangtze sp. nov. were detected in I. granulatus suggesting a relation between tick species and Borrelia species. Furthermore, B. garinii and B. valaisiana were detected from ticks collected from different host species indicating a relation between host species and Borrelia species. Cattle and dogs might be reservoirs for B. garinii and S.scrofa, cattle, A. agrarius, and R. niviventer might be reservoirs for B. valaisiana. The difference in Borrelia species distribution may be also relative to different tick species. Borrelia garinii is considered to be transmitted by birds, but hosts from which ticks were collected did not include birds in our study. As all ticks were adult, it is likely that Borrelia infections of these ticks were acquired during a previous blood meal.The majority of sequences that were most similar to B. burgdorferi s.l. spirochetes would survive the molt, especially for non-Ixodes ticks. Finally, tick species from different sites varied significantly, which might influence infection rates of different sites.There were several limitations to our study. First, the low numbers of ticks of each species in each region collected in different times and from different animals reduced the probabilities of getting useful information from this study. Second, the examined ticks were collected from animals rather than as questing specimens, which brings into question whether H. longicornis and I. sinensis in Zhejiang Province. We detected B. burgdorferi s.l. in diverse species of ticks from different areas. Borrelia burgdorferi s.l. detected were similar to B. garinii, B. valaisiana, or B. yangtze sp. nov., which can cause human infections, indicating that B. burgdorferi s.l. infections might be largely unrecognized and these infections may be frequent in Zhejiang Province.In conclusion, the dominant tick species were"} +{"text": "Int. J. Environ. Res. Public Health addressing the so-called \u201cTriangle of Death\u201d linked to waste crisis in the Southern Italy [A recent paper was published on rn Italy . Three drn Italy ,3, chararn Italy , to defirn Italy . The app"} +{"text": "Diurnal preference (chronotype) is a useful instrument for studying circadian biology in humans. It harbours trait-like dimensions relating to circadian period and sleep homeostasis, but also has ontogenetic components (morningness increases with age). We used the Morningness-Eveningness questionnaire (MEQ) in the Baependi study, a family-based cohort study based in a small town in Minas Gerais, Brazil. The population is highly admixed and has a cohesive and conservative lifestyle. 825 individuals aged 18\u201389 years (average \u00b1 SD = 46.4 \u00b1 16.3) and belonging to 112 different families participated in this study. The average MEQ score was 63.5 \u00b1 11.2 with a significant (P < 0.0001) linear increase with age. Morningness was significantly (P < 0.0001) higher in the rural (70.2 \u00b1 9.8) than in the municipal zone (62.6 \u00b1 11.1), and was also significantly (P = 0.025) higher in male (64.6 \u00b1 10.9) than in female (62.8 \u00b1 11.2) participants. Thus, in spite of universal access to electricity, the Baependi population was strongly shifted towards morningness, particularly in the rural zone. Heritability of MEQ score was 0.48 when adjusted for sex and age, or 0.38 when adjusted for sex, age, and residential zone. The reported MEQ score heritability is more akin to those of previous twin studies than previous family studies. Circadian period is viewed as a stable and reproducible quantitative trait in humans23910In addition to its endophenotypic qualities, chronotype is also influenced by state-like variables, some of them of considerable interest to our understanding of the interaction between the circadian oscillator and the sleep homeostat and our external environmentThe Morningness-Eveningness Questionnaire (MEQ) designed by Horne and \u00d6stberg16The general shift towards morningness in the Baependi population as compared to urban ones is shown in 142 \u00b1 standard error) are shown in The estimates of heritability . The variance component model, a well-known tool for heritability estimates in family studies, was used to calculate polygenic heritability estimates for MEQ score using the approach implemented in the kinship2 package in the R software environment.The basic descriptive statistical including means and standard deviations, were estimated using the R program adjusted by age, gender and place of residence . The results are described in In the most narrow sense, the heritability of a trait represents the proportion of the phenotypic variance attributable to addictive genetic effects and is given by hM.v.S., J.E.K., M.P., H.V., A.B.N. and A.C.P. designed the research, M.v.S., T.P.T., A.R.V.R.H., N.E.D. and A.B.N. performed it, M.v.S., A.R.V.R.H. and N.E.D. analysed the data, M.v.S., T.P.T., A.R.V.R.H., N.E.D., M.P., A.B.N. and A.C.P. wrote the main manuscript text. M.v.S. prepared Figures 1\u20133 and N.E.D. prepared Figure 4. All authors reviewed the manuscript."} +{"text": "Scientific Reports5: Article number: 12341; 10.1038/srep12341 published online: 07242015; updated: 10202015.In this Article, the Figure labels were omitted from Figure 1. The correct In addition, there is a typographical error in the Acknowledgements section.\u201cHT also thanks Prof. S. Qiao of Fudan University, China, and Prof. K. F. Kelly of Rice University, USA, for fruitful discussions and Profs. K. Maeda and Y. Horibe of Kyutech, Japan, for support with the experiments.\u201dshould read:\u201cHT also thanks Prof. S. Qiao of Fudan University, China, and Prof. K. F. Kelly of Rice University, USA, for fruitful discussions and Profs. T. Maeda and Y. Horibe of Kyutech, Japan, for support with the experiments.\u201d"} +{"text": "Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.A comparative analysis of the genomes of primates, including species in the genus Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.Our results highlight the importance of changes in miRNA gene sequences in the course of Using improved versions of the H. s. d. and H. s. n. genomes, we performed computer-assisted comparisons of the H. s. n., H. s. d. and H. s. s. genomes to reveal the structural and functional organization of microRNAs (miRNAs) as well as the mRNAs targeted by these miRNAs. In both the Neanderthal and Denisovan genomes, we found miRNA genes with fixed substitutions in mature miRNAs and multiple substitutions in pre-miRNA regions involved in pre-miRNA processing.Early in the 21 in 2010 . The Homulations . It was H. s. d. -10, we aOur analysis of spatiotemporal gene expression in human tissues demonstrated that the miRNAs bearing new genetic variants fixed in the Denisovan genome regulated target mRNAs with the highest levels of expression in the postnatal human brain.H. s. s. miRNAs from the miRBase database rel. 19 [H. s. d. and H. s. n. pre-miRNAs with highly confident sequences that are orthologous to H. s. s. pre-miRNAs. Using the selection procedure described in the Methods section (Selection of miRNA genes in H. s. d. and H. s. n. with no match in H. s. s.), we identified 1298 H. s. d. and 1329 H. s. n. pre-miRNAs perfectly matched to H. s. s. pre-miRNA gene sequences. In addition, we identified and selected for further study 106 H. s. d. and 102 H. s. n. diverged genes for pre-miRNA sequences, which were different from H. s. s. pre-miRNA genes by at least a single nucleotide. The other 191 H. s. d. and 164 H. s. n. pre-miRNAs did not pass quality sequence control in the selection procedureTo identify miRNA genes that evolved divergently in the genus Homo, we first used the map and pre-miRNA gene sequence data for 1595 experimentally confirmed rel. 19 . We seleH. s. d. and H. s. n. pre-miRNA genes non-identical to H. s. s. orthologs had at least one ortholog in another primate. This result indicated that these pre-miRNA coding genes were present in the genome of the common ancestor of H. s. s., H. s. d. and H. s. n. long before the evolutionary split between these hominines. In following up this analysis, we confirmed the existence of orthologs for all selected H. s. d. and H. s. n. miRNA genes except one H. s. d. miRNA gene.Further, we explored the alignment of the genomes of six primates available in Ensembl rel. 69 . Each ofH. s. d. and H. s. n. (see Methods section). Then, we mapped the remaining genetic variants found in the pre-miRNA genes of H. s. d. and H. s. n. onto the secondary structures of the corresponding pre-miRNAs in H. s. s. available at the miRBase rel. 19 [H. s. d. and H. s. n. pre-miRNAs with (i) nucleotide substitutions in the regions corresponding to the sequences of mature miRNAs (and/or miRNAs*) responsible for binding to target mRNAs or (ii) multiple (two or more) densely spaced substitutions within a pre-miRNA region involved in pre-miRNA processing. From these pre-miRNA groups, we excluded the pre-miRNAs that occur in the H. s. s. genome in more than one copy. The aim of this exclusion was to select pre-miRNAs with unique functions. The selection yielded H. s. d. and H. s. n. pre-miRNAs with nucleotide substitutions that might contribute to significant functional differences from the H. s. s. pre-miRNAs.Next, we analyzed all substitutions found in the archaic hominine miRNA genes selected as described above. First, we excluded a few doubtful nucleotide substitutions observed in the sequencing data for the pre-miRNA genes of rel. 19 . We seler\u2264-0.9 [The functional annotation of the diverged pre-miRNA genes in archaic hominines was performed as follows. First, we selected the miRNAs expressed in the central nervous system (CNS) using the miRGator 3.0 and ChIPr\u2264-0.9 . We usedr\u2264-0.9 , and manr\u2264-0.9 . Howeverr\u2264-0.9 . Third, r\u2264-0.9 and the r\u2264-0.9 . We emplr\u2264-0.9 .H. s. d. lineage. The second group includes 5 miRNAs with fixed mutations unique to the H. s. n. lineage. Two other miRNA gene groups were compiled of 14 H. s. d. and 18 H. s. n. miRNA genes bearing variants that match to one of the polymorphic alleles in H. s. s. Most polymorphisms in these miRNAs are SNPs (single nucleotide polymorphisms). Several substitutions are observed in the seed region . For this purpose, we used data in (1) the BrainSpan Exon microarray (BrainSpan) and (2) H. s. d. are enriched in the postnatal stage of brain development, whereas mRNAs targeted by miRNAs bearing fixed mutations specific for H. s. n. are most abundant in the prenatal brain : 1260 target genes for H. s. n. and 1547 for H. s. d. (excluding targets of hsa-mir-671-3p miRNA that possess specific variants common for H. s. d. and H. s. n.). In addition, the number of targeted genes is similar between H. s. n. and H. s. d. miRNAs matched to polymorphic variants in H. s. s. (Ensembl gene IDs): 4072 target genes for H. s. n. and 3653 for H. s. d. It is interesting that the highest expression of transcripts targeted by miRNAs with polymorphisms unique for H. s. d. is confined to the broad thalamus regions and the prefrontal cortex ). Given that the largest number of gene targets was found for the polymorphic hsa-mir-149 (5p) miRNA for all fine brain structures except two: the fusiform gyrus for H. s. d. miRNAs and the precentral gyrus for H. s. n. miRNAs. The picture obtained based on the target mRNAs for miRNAs expressed in the central nervous system tissues with known human polymorphisms enriched in target genes of H. s. d. and the developmental category enriched in target genes of such H. s. n. miRNAs. It would be reasonable to speculate that that the evolutionary changes in miRNA-transregulators might contribute to alterations in functional activities in specific brain regions in Denisovans, whereas in Neanderthals, the mutations in miRNAs could promote alterations in brain development and structure.In addition to the identification of target brain structures for n system and the H. s. d. and 31 genes for H. s. n. Almost one-third of those genes contain variations specific for archaic humans (11 genes for H. s. d. and 9 for H. s. n.). The analysis of human gene expression data resulted in 9 H. s. d. and 5 H. s. n. genes with specific archaic variations and the expression of their human orthologs in the central nervous system.In this work, we identified miRNA genes of archaic humans bearing sequence variations in comparison with the modern human genome sequence: 29 genes for H. s. d. miRNAs with fixed mutations are confined to the thalamus and the prefrontal cortex , no large brain regions are targeted by H. s. n. miRNAs with specific mutations. The only small brain regions targeted by H. s. n. miRNAs with such mutations are the superior lateral aspect and the central sulcus of the precentral gyrus.The detailed analysis of the human brain gene expression data demonstrated that the brain regions with the most abundant expression of mRNAs targeted by the H. s. d. were expressed predominantly in the later prenatal and early postnatal development stages. Targets for miRNAs with mutations specific for H. s. n. were expressed predominantly in early prenatal brain development stages. These results may reflect a potential association between the changes in the Denisovan miRNA genes reported in this study and the brain development of H. s. d., which likely allowed them to reach their high level of craftsmanship.We identified differences in gene expression pattern during human brain development for the targets of human orthologs for the selected miRNAs. Targets for miRNA genes with mutations specific for H. s. s. pre-miRNAs in the miRBase database rel. 19 [H. s. d. and H. s. n. pre-miRNAs orthologous to H. s. s. pre-miRNA genes. The H. s. d. and H. s. n. genomes appear as short nucleotide sequences (reads) mapped onto the human genome [H. s. d. and H. s. n. pre-miRNAs would remain, we used filtering methods.We used data on the chromosomal localization of 1595 experimentally confirmed rel. 19 and selen genome . To ensuH. s. d. and H. s. n. pre-miRNAs were combined from reads with a quality of mapping onto H. s. s. pre-miRNA genes not less than 15 [(I) The consensus sequences of than 15 .H. s. d. and H. s. n. pre-miRNAs included only those read nucleotides (a) for which the Phred sequence quality [(II) The consensus sequences of quality was not quality and (b) quality .(III) Any position in the consensus with coverage of less than 5 was assumed to be undetermined .H. s. d. and H. s. n. pre-miRNAs with undetermined positions were discarded.(IV) The consensus sequences of H. s. d. and H. s. n. pre-miRNAs that (a) had nucleotide substitutions that H. s. s. lacked and (b) were combined from reads mapped onto the human genome with a quality of less than 30 were discarded [(V) The consensus sequences of iscarded ,3.H. s. d. and H. s. n. pre-miRNAs, only those alternative states that (a) had comparable frequencies (the difference between the frequencies would not exceed 1.3) and (b) passed filtering stages I-V were considered.(VI) If there were two or more polymorphic states at a consensus position in H. s. d. and H. s. n. pre-miRNAs for the presence of PCR artifacts. We did not find any PCR artifacts in the positions of selected H. s. d. and H. s. n. pre-miRNAs.(VII) Additionally, we manually analyzed all mapped reads of selected H. s. s., H. s. d. and H. s. n. we analyzed the multiple genome alignment of six primates from Ensembl rel. 69 [H. s. s. pre-miRNA.To select pre-miRNA coding genes that were present in the genome of the common ancestor of rel. 69 . The minH. s. s./H. s. d. and H. s. s./H. s. n. pairs onto the secondary structures of the corresponding pre-miRNAs in H. s. s. contained in the miRBase database rel. 19 [We mapped all the nucleotide substitutions found by comparing the pre-miRNA orthologs in the rel. 19 .H. s. d. and H. s. n. pre-miRNA genes with (i) nucleotide substitutions in the regions corresponding to the sequences of mature miRNAs (and/or miRNAs*) or (ii) multiple substitutions within a region not larger than 1/20 of the pre-miRNA length. In the first case (i), the altered mature miRNAs are of special interest because they change the pattern of complementary interactions between miRNAs and their target mRNAs in H. s. d. or H. s. n. and make it different from H. s. s. In the second case (ii), the probability of observing multiple changes within a small region of H. s. d. or H. s. n. pre-miRNA by random chance is extremely low. For instance, the estimate of the total number of differences between H. s. d. and H. s. s. is approximately 1,650,000 [We selected ,650,000 . Under tH. s. d. and H. s. n. DNA (see steps V and VI of the filtering protocol), considering their tetranucleotide context. Thus, we used data in the UCSC Genome Browser phyloP46way to select evolutionarily conserved regions of the human genome . The occurrence of the polymorphic variants of the consensuses in the H. s. d. and H. s. n. genomes was then assessed considering their tetranucleotide context. We selected pre-miRNAs with mutations that either do not occur in the 454,775,413-strong selection of evolutionary conservative positions analyzed (p \u2264 2\u00b710-9) or are single occurrences (p = 2\u00b710-9).To ensure that the mutations in our selection of miRNAs were not DNA sequencing errors, we analyzed the frequencies of all polymorphic consensuses of H. s. d. and H. s. n. short reads alignment on a reference H. s. s. genome (hg19). We found no traces of the PCR amplification of short reads in miRNA genome positions: any single read in these positions started and stopped at unique genome locations.To ensure that the mutations in the set of selected miRNAs were not a result of PCR amplification in DNA sequencing (see step VII of the filtering protocol), we performed a manual analysis of H. s. s. genome .Using the blastn program in BLAST 2.2.26+ [H. s. s. miRNA, we identified the genes encoding its target mRNAs. This identification was performed using miRGator 3.0 [r<-0.9) and the ChIP-seq data for H3K4me3 histones marking active promoters in primate cortical neurons [For each orthologous ator 3.0 denote the set of human mRNAs expressed in the k-th tissue and targeted by all known human miRNAs. It should be noted that the overwhelming majority of genes in the human genome (~20000) [W(k) as the set of all human mRNAs expressed in the k-th tissue. W(Qk) denotes the subset of target mRNAs regulated in the k-th tissue by the miRNA pool, Q, and J(Qk) denotes the size of this subset.Let (~20000) can be t(~20000) ,30,34. TQ, on mRNAs with expression in the k-th tissue was estimated using the following formula:The regulatory potential, j-th target mRNA in the subset W(Qk) in the k-th tissue, and k-th tissue (or brain structure) by mature miRNAs in the pool Q and characterizes its post-transcriptional regulatory potential in that tissue.Here, rainSpan or AHBA[rainSpan . The LkQQ, we selected the ones with the highest regulatory potential k-th tissue, W(k). To estimate the significance of the difference between the pool's Q regulatory potential and the background, we used a resampling test /2 mRNAs from the set W(Qk) of human mRNAs targeted by miRNAs in the pool Q (the W(Qrandk) subset). For the W(Qrandk) subset, we calculated 5 times. We estimated the mean and standard deviation of the W(Qk) subset allowed us to account for uncertainties in miRNA annotation .First, we performed random sampling without replacement of W(k) set of all miRNA targets expressed in the k-th tissue. For this purpose, we selected J(Qk)/2 mRNAs from the W(k) randomly without replacement. We termed this subset W(randk). We calculatedSecond, we performed sampling of mRNAs from the background distribution, using the j-th target mRNA in the subset W(randk). This procedure was repeated 105 times and allowed us to estimate the mean and standard deviation of krandL.as the estimate of the background miRNA regulatory potential; here, krand Land d statistic [p-value of t-statistic. The difference between the krand Land p-value less or equal to 0.01, implying that the k-th tissue was targeted by the miRNAs from the pool Q. It is important to note that the data resampling approach described above does not rely on distributional assumptions and simultaneously allowed us to control Type I error, and corrects for any hidden data correlation [p-value threshold directly.We calculated the difference between the e value) ,36. The relation -39. TherThe authors have declared that no competing interests exist.K.V.G., A.D.A. and E.I.R. conceived the project. K.V.G. performed all data analysis. N.A.K., E.I.R. and A.P.D. coordinated the project. All authors contributed to the final manuscript preparation, discussed the results and their implications, and have read and approved the final manuscript."} +{"text": "Human Behavior and Environment and Advances in Environment, Behavior and Design\u2014the field of environmental psychology suffered a loss. Scholars could go to one of the edited Plenum books to find state-of-the-art reviews on existing and emerging areas of research. When Behavioral Sciences approached me to guest edit a Special Issue on Advances in Environmental Psychology, I saw it as a chance to revive the lost resource. I checked with Behavioral Sciences to ensure that I would have complete control over the editing process and the range of human responses addressed in the field. These connections and related responses include, but are not limited to, environmental perception and cognition; environmental attitudes and appraisals; environmental stress, noise, and crowding; responses to disasters, settings, personal space, territoriality, and privacy; crime and fear of crime; behavioral change; home, neighborhood, work, and educational environments; and facility planning and evaluation. Articles appropriate for the Special Issue include historical perspectives, theoretical articles, and reviews of research in a topic area, or discussions of a program of empirical research in an area. Papers that examine the relations between humans and their surroundings with planning, design or policy implications would represent excellent fits. This Special Issue aims to explore the state of knowledge in the field and the application of that knowledge to creating better places for people.\u201dBehav. Sci. 5(2), 190\u2013202.Rollings, A. K., Wells, N. M. and Evans, G. 2015. Measuring neighborhood quality related to health. Behav. Sci., 5(1), 121\u2013153.N. L. Mihavlov and D. D. Perkins. 2015. Local environmental grassroots activism: Contributions from environmental psychology, sociology and politics. Behav. Sci, 5(1), 1\u201326.Reybrouck, M. 2015. Music as environment: An ecological and biosemiotic approach. Behav. Sci., 4(4), 448\u2013470.Stamps, A. A. 2014. Protocol for evaluating contextual design principles. Behav. Sci., 4(4), 423\u2013436.Devlin, A. S. 2014. Wayfinding in healthcare facilities: contributions from environmental psychology. Behav. Sci. 4(4), 394\u2013409.Berto, R. 2014. 2014. The role of nature in coping with psycho-physiological stress: a literature review on restorativeness. Behav. Sci., 4(4), 371\u2013393.Heft, H., Hoch, J. Edmunds, T. and Weeks, J. 2014. Can the identity of a behavior setting be perceived through patterns of joint action? An investigation of place perception. Behav. Sci., 4(4), 341\u2013351.Terzano, K. 2014. Commodification of transitioning ethnic enclaves. Each of the eight published manuscripts went through a rigorous review process (with two or more expert reviewers). As an urban planner/urban designer, I am interested in neighborhood and urban issues. Some papers touch on such issues, but others deal with smaller scale building and setting issues. Some center more on theory and others more on practical applications. The accepted papers include:"} +{"text": "The authors wish to make the following changes to their paper .Author ListOriginal:1, Ming-Jen Cheng 1,*, Jih-Jung Chen 2,3,*, Nanthaphong Khamthong 4, Wen-Wei Lin 5 and Yueh-Hsiung Kuo 3,5,6,7Ming-Der Wu 1 Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan 2 Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University (NYCU), Taipei 112, Taiwan3 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; yhkuo800@gmail.com4 College of Oriental Medicine, Rangsit University, Pathum Thani 12000, Thailand; nanthaphong.k@rsu.ac.th5 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; yang341203@gmail.com6 Department of Biotechnology, Asia University, Taichung 413, Taiwan7 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan* Correspondence: chengfirdi@gmail.com (M.-J.C.); jjungchen@nycu.edu.tw (J.-J.C.)To be replaced with:1,\u2020, Ming-Jen Cheng 1, Jih-Jung Chen 2,3, Nanthaphong Khamthong 4, Wen-Wei Lin 5,\u2020 and Yueh-Hsiung Kuo 6,7,8,*Ming-Der Wu 1 Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan; wmd@firdi.org.tw (M.-D.W.); chengfirdi@gmail.com (M.-J.C.)2 Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University (NYCU), Taipei 112, Taiwan; jjungchen@nycu.edu.tw3 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan4 College of Oriental Medicine, Rangsit University, Pathum Thani 12000, Thailand; nanthaphong.k@rsu.ac.th5 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; yang341203@gmail.com6 Department of Biotechnology, Asia University, Taichung 413, Taiwan7 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan8 Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan* Correspondence: kuoyh@mail.cmu.edu.tw\u2020 These authors contributed equally to this work.Author ContributionOriginal:Y.-H.K., J.-J.C. and M.-J.C. designed the research; N.K., M.-D.W.,W.-W.L. and M.-J.C. performed the research; N.K. conducted biological assays, J.-J.C., Y.-H.K. and M.-J.C. helped with structure elucidation; M.-J.C. organized the data and wrote the paper. All authors have read and agreed to the published version of the manuscript.To be replaced with:Y.-H.K. is responsible for the main research framework; Y.-H.K. and M.-J.C. designed the research; W.-W.L. performed the chemical research; N.K. and M.-D.W. conducted antimicrobial assays, J.-J.C., Y.-H.K. and M.-J.C. helped with structure elucidation; Y.-H.K. and M.-J.C. organized the data and M.-J.C. wrote the paper. All authors have read and agreed to the published version of the manuscript.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "CRISPR/Cas systems have been widely used for genome engineering in many plant species. However, their potentials have remained largely untapped in fruit crops, particularly in pear, due to the high levels of genomic heterozygosity and difficulties in tissue culture and stable transformation. To date, only a few reports on the application of the CRISPR/Cas9 system in pear have been documented, and have shown very low editing efficiency. Here we report a highly efficient CRISPR toolbox for loss-of-function and gain-of-function research in pear. We compared four different CRISPR/Cas9 expression systems for loss-of-function analysis and identified a potent system that showed nearly 100% editing efficiency for multi-site mutagenesis. To expand the targeting scope, we further tested different CRISPR/Cas12a and Cas12b systems in pear for the first time, albeit with low editing efficiency. In addition, we established a CRISPR activation (CRISPRa) system for multiplexed gene activation in pear calli for gain-of-function analysis. Furthermore, we successfully engineered the anthocyanin and lignin biosynthesis pathways using both CRISPR/Cas9 and CRISPRa systems in pear calli. Taking these results together, we have built a highly efficient CRISPR toolbox for genome editing and gene regulation, paving the way for functional genomics studies as well as molecular breeding in pear. CRISPR/YAO, andthe egg-cell specific promoter 453. This work was also supported by the National Science Foundation Plant Genome Research Program grant (IOS-1758745) to Y.Q. H.L, J.C., and R.T. were supported by a scholarship from the National Training Program of Innovation and Entrepreneurship for Undergraduates (202110307017). We thank the Centre of Pear Engineering Technology Research, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University for supporting this project.J.W. and M.M. designed the experiments. J.W. and Y.Q. supervised the research. M.M, C.P., and Y.Z. generated all the vectors. M.M., H.L., Z.Y., J.C., R.T., and J.L. performed the stable transformation of pear calli and plants. M.M. did all genotyping and phenotyping analysis with the help of C.S. and Y.X. J.W., Y.Q., and M.M. wrote the paper with input from other authors. All authors read and approved the final manuscript.The high-throughput sequencing data sets have been submitted to the National Center for Biotechnology information (NCBI) database under Sequence Read Archive (SRA) BioProject ID PRJNA787753.The authors declare that they have no conflicts of interest.Horticulture Research online.Web_Material_uhac148Click here for additional data file."} +{"text": "Apis mellifera iberiensis), the dark honey bee (Apis mellifera\u00a0mellifera), both belonging to the M lineage, and the Carniolan honey bee (Apis mellifera carnica), belonging to the C lineage. DeepWings\u00a9 classification of these colonies largely matched the endemic M and C lineages, with proportions of 71.4% and 97.6%, respectively. At the subspecies-level the matching proportions were 89.7% for the Iberian honey bee, 41.1% for the dark honey bee and 88.3% for the Carniolan honey bee, which can be explained by DeepWings\u00a9 sometimes confounding closely related subspecies and, more importantly, by genetic pollution. A comparison between DeepWings\u00a9 data and molecular data revealed that the agreement between the two is weaker when there is genetic pollution. Our results suggest that DeepWings\u00a9 is a valuable tool for honey bee identification, which can be used not only for breeding and conservation but also for research purposes.Wing venation traits are used to identify honey bee subspecies. While several wing-based tools are available, they suffer from weaknesses that were addressed by the recently developed software DeepWings\u00a9. This software allows fully automated identification of wing images in a friendly, free, and rapid manner. Here, we sought to test DeepWings\u00a9 on 14,816 wing images representing 2601 colonies sampled in the native areas of three widespread subspecies in Europe: the Iberian honey bee of DeepWings\u00a9 on 14,816 wing images with variable quality and acquired by different beekeepers and researchers. These images represented 2601 colonies from the native ranges of the M-lineage A. m. iberiensis and A. m. mellifera, and the C-lineage A. m. carnica. In the A. m. iberiensis range, 92.6% of the colonies matched this subspecies, with a high median probability (0.919). In the Azores, where the Iberian subspecies was historically introduced, a lower proportion (85.7%) and probability (0.842) were observed. In the A. m mellifera range, only 41.1 % of the colonies matched this subspecies, which is compatible with a history of C-derived introgression. Yet, these colonies were classified with the highest probability (0.994) of the three subspecies. In the A. m. carnica range, 88.3% of the colonies matched this subspecies, with a probability of 0.984. The association between wing and molecular markers, assessed for 1214 colonies from the M-lineage range, was highly significant but not strong . The agreement between the markers was influenced by C-derived introgression, with the best results obtained for colonies with high genetic integrity. This study indicates the good performance of DeepWings\u00a9 on a realistic wing image dataset.DeepWings\u00a9 is a software that uses machine learning to automatically classify honey bee subspecies by wing geometric morphometrics. Here, we tested the five subspecies classifier ( Apis mellifera L. (Hymenoptera: Apidae), differentiated into over 30 subspecies [A. m. mellifera and A. m. iberiensis, it spreads across a wider geographical and climatically more diverse area than the other six subspecies of C-lineage ancestry. This area extends from the Iberian Peninsula to southern Scandinavia and from Britain and Ireland to the Ural Mountains [A. m. carnica and A. m. ligustica. These, together with the O-lineage A. m. caucasia, were introduced worldwide due to their perceived gentle behavior and high productivity [A. m. mellifera was threatened by gene flow from those foreign subspecies [A. m. mellifera gene pool, conservation efforts sprouted in Europe [Apis melliferae melliferae) for its protection was founded in 1994. These efforts require tools to identify colonies before they can be moved to conservation areas or to monitor the efficiency of isolated mating stations. On the other hand, identification tools may also be useful to C-lineage queen breeders in Eastern and Southeastern Europe.The honey bee, bspecies ,2,3,4,5,uctivity ,7,8,9,10bspecies ,12,13,14n Europe and an aThe molecular tool kit for honey bee identification includes different markers of the mitochondrial and nuclear DNA ,23,24,25A. m. mellifera [http://www.hockerley.plus.com/ accessed on 1 July 2022 ) or CBeeWings (http://www.cybis.se/cbeewing/ accessed on 1 July 2022). The problem is that these software packages provide a less reliable identification than that obtained from character-intensive methods. In addition, they require manual annotation of the vein junctions from which the indexes are calculated, which is time-consuming and prone to error. Subspecies identification by classical morphometry comprises 42 characters, including the size of anatomical structures, such as proboscis, femur, tergite, and sternites; discrete classes of pigmentation; length and width of wings, and angles in wing venation . Howeverellifera as they https://deepwings.ipb.pt. (accessed on 1 November 2022)Another way of assessing wing shape variation is through wing geometric morphometrics (WGM). This method is recognized as robust and reliable in insect taxonomy and is widely used in honey bee subspecies identification for varying purposes, including conservation ,40,41,42A. m. iberiensis, A. m. mellifera and A. m. carnica. In addition, we compared the wing shape data with molecular data for a subset of A. m. iberiensis and A. m. mellifera colonies. Our objectives were (i) to evaluate the functionality of DeepWings\u00a9 when processing a massive number of wing images of varying quality and produced by different persons; (ii) to assess how closely the colonies identified by DeepWings\u00a9 matched the endemic subspecies distribution, with an emphasis on M-lineage subspecies; and (iii) to assess the association between the identification produced by DeepWings\u00a9 and that inferred from molecular markers.Herein, we employed DeepWings\u00a9 to identify 2601 colonies from the analysis of 14,816 wings. These colonies were located in 15 countries, covering the native ranges of A. m. iberiensis , A. m. mellifera , and (ii) C-lineage subspecies A. m. carnica . Samples were collected from hives, except for Hungary and Poland, where the great majority were collected from flowers. However, these samples most likely represent independent colonies, given the > 3 km distance between sampling locations. Some of the samples of A. m. mellifera were collected from protected apiaries and A. m. mellifera . For each colony, the highest prediction probability of belonging to M lineage, as inferred from the 19 landmark coordinates using DeepWings\u00a9, was compared against the corresponding M-lineage membership proportion, as inferred from different sets of microsatellites or SNPs (The association between DeepWings\u00a9 classification and that obtained from molecular markers (microsatellites and SNPs) was assessed for 1214 colonies sampled from the native ranges of or SNPs using th or SNPs . p) adjusted by Bonferroni. The association between the probability of belonging to the M lineage, as inferred by DeepWings\u00a9 from wing shape data, and the membership proportion in the M lineage, as inferred from microsatellite or SNP data, was assessed using the Spearman\u2019s rank-order correlation coefficient (r). All statistical tests were conducted on Graph Pad Prism version 5.01 for Windows, GraphPad Software, San Diego, CA, USA.The probability data obtained from the average wing for the subspecies identified by DeepWings\u00a9 did not follow a normal distribution, as per the Kolmogorov\u2013Smirnov test. Accordingly, the summary statistics were presented for each location as medians and interquartile ranges were rejected by the software as the 19 landmarks could not be annotated due to different image problems . The rejA. m. mellifera and the lowest for wings identified as A. m. caucasia . Analysis of the 2488 colonies further confirmed this pattern, with A. m. mellifera reaching a median of 0.994 (0.075) and A. m. caucasia 0.636 (0.334). This result makes sense, as colonies were not sampled in the native distribution of the Caucasian subspecies.The final sample sizes identified by the five-subspecies classifier of DeepWings\u00a9 were 13,960 for wings and 2488 for colonies. Each wing was classified into the subspecies that showed the highest prediction probability, ranging from as low as 0.300 to 1.000, with a median of 0.968. The classification results at the colony level (inferred from the average wing) were similar, as the highest probability ranged from 0.309 to 1.000, with a median of 0.944. The highest median probability was obtained for wings identified as A. m. iberiensis, A. m. mellifera, and A. m. carnica, for the top two probabilities and for an arbitrary 0.950 probability threshold. For the sake of this table presentation, all the colonies from the Azores were included in the range of A. m. iberiensis, as this subspecies was originally introduced by the Portuguese settlers in historical times [A. m. mellifera, as the great majority of them originated from elsewhere. Finally, all the colonies from Romania were included in the range of A. m. carnica, as the other native subspecies of Romania, A. m. macedonica [A. m. carnica native range. As shown in A. m. iberiensis for both wings (77.2%) and colonies (89.7%) and the lowest for A. m. mellifera . However, when the 0.950 threshold was applied, the highest proportions of wings (86.7%) and colonies (97.3%) assigned to the expected subspecies were obtained for A. m. carnica in its native range.al times . DespiteA. m. carnica (17 wings) and A. m. caucasia (13 wings) were only identified at the individual wing level. When the classification was conducted at the colony level, these two subspecies were no longer detected. Because colony-level classification is more meaningful for apiculture than individual-level classification, the following results will be presented only for colonies. Furthermore, the common practice of wing-based identification is to average out intra-colony variation through analysis of multiple wings per colony [The classification proportions of wings and colonies calculated using the highest prediction probability are shown by country in r colony .A. m. iberiensis native range, 603 (92.6%) were classified as A. m. iberiensis, with a median probability of 0.919 (0.225). A higher proportion was found in Portugal (95.7%) than in Spain (91.8%), with median probabilities of 0.935 (0.210) and 0.918 (0.226), respectively and 38 (7.4%) colonies in Portugal and Spain, with median probabilities of 0.976 (0.141) and 0.998 (0.005), respectively. While in Portugal, no differences were found in the distribution of the classification probabilities between the two M-lineage subspecies , in Spain, A. m. mellifera showed an unexpectedly higher median probability . A. m. ligustica was also detected in Iberia, although with a residual proportion (0.5%) and a low median probability . A. m. carnica and A. m. caucasia colonies were detected exclusively in Spain, with the former representing only one colony (0.2%), with a probability of 0.994, and the latter representing two colonies (0.4%), with a median probability of 0.520 (0.172). When analyzed at the lineage level, nearly all colonies (99.1%) were assigned to the expected M-lineage.Of the 651 colonies sampled in the ectively . The secA. m. iberiensis was also the most frequently identified subspecies on six of the eight sampled islands than for Terceira , but these were not significantly different from the median probabilities obtained for A. m. iberiensis in both islands . A low proportion of A. m. ligustica was also detected on Pico, although with a significantly lower median probability than that obtained for A. m. iberiensis .In the Azores, islands , althoug islands . The higA. m. mellifera native range, 414 (41.1%) were classified as A. m. mellifera, with a median probability of 0.994 (0.082). Except for Avignon (France), Wales (UK), and Poland, the remaining locations had a high proportion of colonies classified as A. m. mellifera . In Russia, 50 (96.2%) colonies showed high classification probabilities for A. m. mellifera , and only two were classified as A. m. iberiensis and A. m. ligustica, but with low probabilities: 0.571 and 0.537, respectively. A lower proportion of colonies from Ouessant , Groix , Ireland , Switzerland , and Sweden were classified as A. m. mellifera, despite their high probabilities . In these locations, A. m. iberiensis was the second most frequently identified subspecies, with a lower median probability in Ireland and Groix . Therefore, when classified at the lineage level, most colonies (>93.0%) matched the expected M lineage (Of the 1008 colonies sampled in the ellifera . The two lineage . A. m. mellifera (A. m. carnica (44.5%) more frequently than as A. m. ligustica (14.1%) or A. m. caucasia (5.5%), with a significantly higher median probability of 0.983 (0.148) vs. 0.855 (0.268) or 0.641 (0.316), respectively. In contrast, in Wales, colonies classified as A. m. caucasia (23.5%) were more frequent than A. m. ligustica (11.8%) or A. m. carnica (5.9%).A high proportion of colonies from Avignon (63.2%), Wales (41.2%), and Poland (64.1%) had average wings more similar to subspecies of C- and O-lineage ancestries than to ellifera . In PolaA. m. carnica native range, 325 (88.3%) were classified as A. m. carnica, with a median probability of 0.984 (0.089). The highest proportion was found in Slovenia (95.2%), with a median probability of 0.993 (0.040), followed by Romania (91.1%), with a median probability of 0.989 (0.117), Croatia (90.6%), with a median probability of 0.983 (0.058), Hungary (84.1%), with a median probability of 0.982, (0.121), and finally Moldova (50.0%), with the lowest median probability , as shown in A. m. ligustica were also found in these five countries, but with lower proportions and significantly lower probabilities in Croatia and Romania . In Hungary, the probabilities of colonies classified as A. m. ligustica and A. m. mellifera were similar to those of A. m. carnica (H(2) = 5.245, p = 0.072). Colonies classified as A. m. mellifera (1.9%) and A. m. caucasia (0.5%) were rare (A. m. caucasia in Moldova) and 0.790 .The association between the probability of belonging to the M lineage, as inferred by DeepWings\u00a9 from wing shape data, and the membership proportion in the M lineage, as inferred from microsatellite or SNP data, is shown for all samples and locations in A. m. iberiensis, A. m. mellifera, and A. m. carnica were analyzed using the WGM approach implemented by DeepWings\u00a9. This large and diverse dataset of wing images, originating from such a wide geographical range and acquired using varied image acquisition systems, offered a unique opportunity to test the performance of DeepWings\u00a9 under real conditions. Moreover, the interaction with the numerous wing image contributors (beekeepers and researchers), who have different experiences and needs, allowed us to introduce several improvements in the software. These included (i) estimation of CI, HI, and DSA; (ii) display of the landmark-annotated wing images; (iii) production of a table with the landmark coordinates; (iv) inference of an average wing from a batch of wings, allowing classification of a colony from multiple wings; and (v) display of the three best classifications for the analyzed wings. DeepWings\u00a9 successfully classified 94.2% of the wings, consistent with the rate predicted by the software developers [In this study, 14,816 wings representing 2601 colonies from 15 countries and covering the native ranges of velopers .A. m. mellifera range were often classified as A. m. iberiensis (the reverse was less frequent) and samples collected in the A. m. carnica range were often classified as A. m. ligustica. These findings are not surprising given that subspecies belonging to the same evolutionary lineage share a recent ancestor and are, therefore, genetically closely related [The classification of the European colonies largely matched the endemic M and C-lineages, with proportions of 71.5% and 97.6%, respectively, as the top two probabilities were typically assigned to subspecies sharing lineage ancestry. However, when analyzed at the subspecies level, the matching proportions decreased, as samples collected in the related . Further related ,30,49. M related ,51,52,53 related . Therefo related .A. m. ligustica and A. m. carnica in France, Switzerland, the UK, Ireland, Poland, and Russia, therefore mismatching the expected M lineage, can be explained by beekeeper-mediated gene flow and is consistent with molecular surveys reporting variable C-derived introgression in A. m. mellifera across Europe [A. m. iberiensis detected with high probabilities (> 0.950) in colonies located far from the native range in Iberia was likely confounded by DeepWings\u00a9 with its close relative A. m. mellifera, as international trading of Iberian queens is very uncommon. If this is true, Switzerland and Groix showed a particularly high rate of misclassification, with 33.3% and 30.6% of the colonies labeled as A. m. iberiensis, respectively. In the other locations, the rates were lower (1.9%\u201320.0%), but still higher than expected, considering that DeepWings\u00a9 classification accuracy reported for A. m. mellifera was 0.950% [The detection of wing venation patterns corresponding to the divergent s Europe ,57,58,59s 0.950% . This fis 0.950% .A. m. iberiensis native range were recognized as A. m. mellifera with probabilities above 0.950, indicating that DeepWings\u00a9 performed relatively well. While misclassification of these colonies cannot be ruled out, the detection of wing shapes matching A. m. mellifera can also be explained by the clinal patterns of variation that were recurrently reported for Iberian populations, with populations from northern Spain being genetically closer to A. m. mellifera than populations from southern Spain and Portugal [A. m. iberiensis, it is possible that the probability data reflects genuine variation in the wing venation [In contrast to the findings north of the Pyrenees, only a small proportion of the colonies examined in the Portugal ,31,60,61venation .A. m. iberiensis was introduced in the XVI century [In the Azores, where century , a highe century . Recurre century . RemarkaA. m. carnica and A. m. ligustica, to the O-lineage A. m. caucasia, and to the M-lineage A. m. iberiensis than to A. m. mellifera. While A. m. iberiensis could be confounded with A. m. mellifera, detection of the other three subspecies is compatible with the existence of a natural hybrid zone in southern Poland, where the three lineages come together [A. m. ligustica was unexpected, as molecular studies largely reported in Poland the presence of A. m. carnica, but not of the Italian bee [A. m. mellifera and A. m. iberiensis. Alternatively, but not mutually exclusive, A. m. ligustica genes can were introduced in Poland by undocumented importations of Italian queens and/or by the documented and steadily increasing importations of the artificial strain Buckfast [A. m. ligustica were low, as would be expected in a territory where A. m. carnica is endemic and favored by local beekeepers [A. m. ligustica ancestry [A. m. cecropia and A. m. macedonica) were identified as A. m. ligustica. This could very well be the case of several colonies sampled east and south of the Carpathian mountain ridge in Romania and Moldova, where A. m. macedonica and A. m. carpatica occurs naturally [A. m. ligustica, A. m. caucasia, and even to the other Romania-native subspecies A. m. carnica.Similar to the Iberian wings, most Polish wings classified by DeepWings\u00a9 originate from north\u2013south sampling transects . Yet, thtogether , as welltogether ,63. Howelian bee ,58. Givelian bee , it is pancestry ,66,67,68aturally ,67, thatThe association between wing and molecular data, assessed for the colonies sampled in the M-lineage native range, was highly significant but not very strong. Convergence of the two markers was variable and dependent on the integrity of the gene pools. They largely agreed in Iberia, Groix, Ouessant, Santa Maria, S\u00e3o Miguel, Ireland, and Russia, which are known for harboring honey bee populations with high genetic integrity ,72,73,74While the genetic basis of wing venation is unknown, it is possible that wing traits are encoded by a few genes. Hence, wing markers likely cover a limited portion of the genome variation. In contrast, molecular markers, such as microsatellites and especially SNPs, are widespread across the honey bee genome ,78, and"} +{"text": "Potato spindle tuber viroid (PSTVd) is a naked, circular, single-stranded RNA (356\u2013363 nucleotides in length) which lacks any protein-coding sequences. It is an economically important pathogen and is classified as a high-risk plant quarantine disease. Moreover, it is known that PSTVd is mechanically transmitted by vegetative plant propagation through infected pollen, and by aphids. The aim of this study is to determine the possibility of viroid transmission by potato pathogen Phytophthora infestans (Mont.) de Bary. PSTVd-infected (strain VP87) potato cultivars Gala, Colomba, and Riviera were inoculated with P. infestans isolate PiVZR18, and in 7 days, after the appearance of symptoms, re-isolation of P. infestans on rye agar was conducted. RT-PCR diagnostics of PSTVd in a mixture of mycelia and sporangia were positive after 14 days of cultivation on rye agar. The PSTVd-infected P. infestans isolate PiVZR18v+ was used to inoculate the healthy, viroid-free plants of potato cv. Gala and tomato cv. Zagadka. After 60 days, an amplification fragment of PSTVd was detected in the tissues of one plant of tomato cv. Zagadka by RT-PCR with the primer set P3/P4, indicating successful transmission of PSTVd by P. infestans isolate PiVZR18v+. This result was confirmed by sequencing of the RT-PCR amplicon with primers P3/P4. The partial sequence of this amplicon was identical (99.5 %) to PSTVd strain VP87. RT-PCR showed the possibility of viroid stability in a pure culture of P. infestans isolate PiVZR18v+ after three consecutive passages on rye agar. PSTVd was not detected after the eighth passage on rye agar in P. infestans subculture. These results are initial evidence of potato viroid PSTVd being bidirectionally transferred between P. infestans and host plants Potato spindle tuber viroid (PSTVd) is an economically importantpathogen, classified as a high-risk plant quarantinedisease. According to the European Plant Protection Organization(EPPO), the disease has been reported in 37 countrieson all continents (https://gd.eppo.int/taxon/PSTVD0/distribution). In Russia, and other former Soviet Union regions,PSTVd was detected in about 50\u201370 % of in vitro potatoplants .Natural infections of PSTVd have been found in the field,mainly in solanaceous crops, such as pepino , potato , and tomato . Potato plants infected with PSTVd becomesmaller and show leaf yellowing, and infected tubers becomesmaller and cracked. The reduction in tuber weight dependson the viroid strain, potato cultivar, and length of time theyhave been infected with PSTVd .Furthermore, a reduction in tuber yield of up to 24 % hasbeen reported in cultivar Saco infected with mild strains ofPSTVd, however, severe strain reduced the yield by up to 64 %. In addition to direct losses, it is importantto take into account indirect losses that can be significant dueto the quarantine status.PSTVd belongs to Family Pospiviroidae (1POSPF), GenusPospiviroid (1POSPG) and consists of a naked, circular,single-stranded RNA (356\u2013363 nucleotides in length) \u2013 thesmallest among plant pathogens lacking a protein-codingability \u2013 therefore, it is a parasite of the host transcriptionmechanism .PSTVd has a wide host range of at least 138 species across10 families . The main hosts are from theSolanaceae family . PSTVd is transmitted mechanically, by aphids .Moreover, it was found to be vertically transmitted throughpollen to progeny seeds on potato (Solanum tuberosum) andtomato (S. lycopersicum) and horizontally transmitted throughinfected pollen to other potato and tomato plants .Viruses are common in fungi and oomycetes and someof these viruses share sequence identities with plant virusesbelonging to different families and genera . There are several examples of plant\u2013virus transmissionby phytopathogenic fungi and oomycetes. It was shown thatsoil-inhabiting fungi Olpidium brassicae and O. radicale belongingto Chytridiales and Polymyxa graminis, Spongosporasubterranean, and Synchytrium endobioticum \u2013 belonging tothe order Plasmodiophorales \u2013 transmit plant viruses . Replications of the tobacco mosaic virus weredemonstrated in the phytopathogenic fungi Colletotrichumacutatum, C. clavatum, and C. theobromicola , cucumber mosaic virus was reported in Rhizoctoniasolani , artichoke Italian latent virus, artichoke mottled crinkle virus, potato virus X, potato virus Y,tobacco mosaic virus and cucumber mosaic virus plus its satelliteRNA can replicate and persist in Phytophthora infestansat least through the first subculture .Wei et al. (2019) obtained preliminary data on the possibilitiesof replicating hop stunt viroid (HSVd), iresine 1viroid belonging to the Pospiviroidae and avocado sunblotchviroid (Avsunviroidae) in at least one of phytopathogenicascomycete fungi Cryphonectria parasitica, Valsa mali, andFusarium graminearum\u041eomycete P. infestans causes significant losses to potatoand tomato crops on a global scale. Despite intensive use offungicides, the pathogen is constantly and ubiquitously presentin potato crops. P. infestans is also the most harmful andwidespread tomato pathogen, both in field and greenhouseconditions. This oomycete has a high adaptive potential to thehost plants, which may indicate the formation of competitiverelationships with other potato and tomato pathogens. In thisregard, it is of interest to identify a possible role of P. infestansin transmission of PSTVd to potato and tomato plants.Plant materials. Potato cultivars that, according to our data,were susceptible to both PSTVd strain VP87 and P. infestans \u2013Gala, Riviera, and Colomba and tomato cultivars Zagadka,Moskvich, and Damskiy Palchik were included in the study.These potato and tomato cultivars were registered in theRussian State Register of Breeding Achievements.PSTVd strains. Two intermediate PSTVd strains, VP35(GenBank accession no. LC523658) and VP87 (LC523667),and severe strain FP10-13 (LC523676) deposited in theinternational information database DDBJ (DNA Data Bank ofJapan), Data set \u201cViruses\u201d (http://blast.ddbj.nig.ac.jp/) wereused in the study. These strains were isolated from infectedpotato leaves from the Volga Federal District (VP87 and VP35)and tubers from the Far Eastern Federal District (FP10-13) in2019 .The PSTVd strains were supported on living tomato plantsof Russian cultivars Zagadka, Moskvich, and DamskiyPalchik.Isolate of P. infestans. Isolate PiVZR18 of P. infestans wasused in the experiments on viroid transmission. PiVZR18was isolated from the natural population of P. infestans in theLeningrad Region (northwest of the European part of Russia)in 2018. Eight virulence genes were identified in this isolate on a set of Black\u2019s differentials.Viroid inoculation of plants. Potato and tomato plantswere grown in a growth room at a temperature of 25 \u00b0C witha photoperiod of 16h/8h (day/night) in 2l pots filled with \u201cTerravita\u201d soil. Seven-day germination potato plants and 14-daytomato plants were used for inoculation by PSTVd.To prepare the inoculum, 0.1 g of fresh tomato leaf tissue \u201360 days post inoculation (dpi) with PSTVd strain VP87 \u2013 was ground in 1 ml sodium phosphate buffer (pH 7.0) and filteredthrough cheeseclothFor mechanical inoculation, the cotyledons of tomatowere dusted with carborundum and gently rubbed over thesurface of the leaves with a plastic pestle. Ten microliters ofinoculum was placed on the injured leaf surface and rubbedseveral times with a sterile plastic pestle. The inoculated plantswere incubated for two months at 25 \u00b0C with light intensity.At 60 dpi, the presence of viroid in the inoculated tomatoplants was determined by RT-PCR.To inoculate 7-day potato plants of the cultivars Gala,Riviera, and Colomba, a 0.5\u20131.0 cm longitudinal stemincision was performed with a sterile razor on a stemapex 1, and 10 \u03bcl of the PSTVd VP87 strainsuspension \u2013 obtained as described above \u2013 was applied. Threeplants of each potato cultivar were inoculated and the assaywas repeated three times. In 60 dpi, the presence of PSTVdin the inoculated plants of potato cultivars was determinedby RT-PCR.http://www.bionet.nsc.ru/vogis/download/pict-2022-26/appx5.pdf/Supplementary Materials are available in the online version of the paper:P. infestans inoculation of plants. Isolate PiVZR18 ofP. infestans was cultured on rye agar medium , 20.0 g sucrose,15.0 g agar) for 30 days in the dark at 15 \u00b0C for propagationand morphological observation .Before inoculating the plants, the suspension was incubatedat 12 \u00b0C for 2.5\u20133 h to release zoospores. Upon RT-PCRdetection for viroid infection, both healthy and viroid-infectedtomato and potato plants were inoculated with a suspension ofP. infestans at a concentration of 50.000 zoosporangia in 1 ml.After inoculation, the plants were placed in humid chamberswith a 14 h light period, at 23 \u00b0C during the day and 15 \u00b0Cat night for a period of 13 dpi. To study PSTVd transmissionfrom P. infestans to host plants, when typical symptoms oflate blight appeared, the humid chamber was removed andthe development of P. infestans slowed down. The affectedleaves were removed and the plants continued to grow. Forthe purposes of PSTVd diagnostics, the upper leaves of theplants without late blight symptoms were cut off.Viroid inoculation of P. infestans. Inoculum of PSTVd wasobtained from the infected tomato plants as described aboveand applied to the 14-day P. infestans culture by transferring10 \u03bcl per Petri dish (in the dish center). After inoculation, theculture was left to grow for 15 days at 10 \u00b0C. Then, myceliafrom the periphery and from the center of the colony weretransferred separately to a fresh medium. The culture wasleft in the same conditions for 30 days, after which RT-PCRanalysis was conducted.Isolation of P. infestans from infected potato andtomato plants. Seven days post inoculation (dpi) after thesymptoms of late blight appeared, P. infestans was isolatedfrom the plants. Sections of the infected leaves were placedbetween tuber slices of the healthy cv. Colomba, and at 6 days,mycelium was transferred with a needle to the surface of ryeagar. The isolates were cultured for 30 days at 15 \u00b0C in thedark and then transferred to a fresh medium.Viroid detection and sequencing. We collected theuppermost leaves from the inoculated potato or tomato plants at 60 dpi. PSTVd detection in pure culture of P. infestans wascarried out after 30 days of growing on rye agar. Approximately0.1 g of tissue from leaves or mycelium was used for RNAextraction. Total RNA was extracted using the RNeasy PlantMini Kit as per the manufacturer\u2019sinstructions (http://www.genome.duke.edu/cores/microarray/services/rna-qc/documents/RNeasy_Mini_Handbook.pdf) andsubsequently used for one-step RT-PCR. Primer sets P3/P4 and P1/P2 or68PV-R+87PV-F were used todetect PSTVd. RT-PCR was prepared with the PrimerScriptOne-Step RT-PCR Kit ver 2 reagents in 10 ml following the manufacturer\u2019s instructions.The primer set ITS4/ITS5 was used to detect the ITS region of P. infestans as aninternal control.RT-PCR was carried out on a MyCycler Thermal Cycler at 50 \u00b0C for 30 min, 94 \u00b0C for2 min, followed by 35 cycles of 94 \u00b0C for 30 sec, 60 \u00b0C for30 sec and 72 \u00b0C for 30 sec. An additional elongation step wasperformed at 72 \u00b0C for 5 min followed by storage at 12 \u00b0C.The sizes of the diagnostic fragments of PSTVd and the ITSregion were 360 and 946 bp, respectively.The PSTVd amplicons were sequenced at the BeagleCompany . Alignment and manualediting of nucleotide sequences were performed usingVector NTI Advance 10 software (Thermo Fisher Scientific).The obtained nucleotide sequences were tested for similaritywith PSTVd strain VP87 (LC523667), used in this study,deposited in the international information database DDBJ(DNA Data Bank of Japan), data set \u201cViruses\u201d (http://blast.ddbj.nig.ac.jp/).There is an absence of data on the possibility of replicatingPSTVd in P. infestans and bidirectionally transferring it betweenhost plants and P. infestans. In this study, we investigatedthe possibility of PSTVd transmission (1) from host plants toP. infestans, (2) from P. infestans to host plants, and (3) thepossibility of PSTVd stability in pure cultures of P. infestans.Transmission of PSTVd from host plants to P. infestansFrom potato plants. Upon confirming PSTVd infection intomato plants of cv. Zagadka by RT-PCR, inoculation of threepotato cultivars , using as aninoculum source extracted-sap of tomato infected with PSTVdstrain VP87, was conducted . After 60 days,detection of PSTVd presence in plants of these cultivars wascarried out by RT-PCR with the P3/P4 primer set .The brightest amplicons indicating a high accumulation ofthe viroid were found for cv. Gala and cv. Colomba. Theviroid accumulation was lower in three plants of cv. Riviera.PSTVd-infected and uninfected (control) potato plants wereinoculated with P. infestans isolate PiVZR18. Seven days afterthe appearance of symptoms caused by P. infestans,the pathogen was first re-isolated from these cultivars on tuberslices of healthy cv. Colomba and then transferred to pureculture on rye agar .After culturing of P. infestans isolates on rye agar, PSTVddetection by RT-PCR was conducted with the primer set P3/P4. Amplicons of ~360 bp \u2013 indicating the presenceof PSTVd \u2013 were detected in a mixture of mycelium andsporangia of pure culture of P. infestans isolates aftercolonization on the cultivars Gala, Riviera, and Colomba. To control for the negative results of viroiddetection that are not due to the quality of RNA extractedfrom P. infestans samples, we used PCR with universalprimers ITS4/ITS5 on rDNAs, which are species specific forP. infestans and displayed an amplicon of 946 bp .From tomato plants. The 15 plants of the two tomatocultivars infected with threePSTVd strains were inoculatedwith the P. infestans isolate PiVZR18 to confirm the resultsobtained. Seven days after the appearance of the symptomscaused by P. infestans, 15 cultures of the pathogen werere-isolated from these plants, first on tuber slices of healthycv. Colomba. After mycelial overgrowth on the surface of tuberslices, the first detection of viroid presence in the myceliumwas performed. Out of 15 isolates, the brightest fragmentindicating viroid infection of mycelium was detected with theprimer set P3/P4 in the P. infestans isolate from cv. Moskvichinfected with PSTVd strain VP87 . PositivePSTVd detection was also obtained for cv. Damskiy Palchik,infected by PSTVd strain VP87 (line 4) and for the isolatesfrom cv. Moskvich infected by PSTVd strain FP10-13(lines 6\u20138) and by strain VP35 (lines 10\u201313). Weak ampliconswere obtained in lines 3, 5, 9, 14, which indicates a low initialconcentration of PSTVd in P. infestans mycelium obtainedfrom the host plant .PSTVd transmission from P. infestans to host plantsThe PSTVd-infected P. infestans isolate PiVZR18v+ was usedto inoculate the healthy, viroid-free plants of potato cv. Galaand tomato cv. Zagadka.After 60 days, an amplification fragment of PSTVd wasdetected in the tissues of one plant of tomato cv. Zagadkaby RT-PCR with the primer set P3/P4, indicating successfultransmission of PSTVd by P. infestans isolate PiVZR18v+.The detection of PSTVd in the RNA of cv. Zagadkainoculated with the P. infestans isolate PiVZR18v+ was confirmed by sequencing of the RT-PCR amplicon withprimers P3/P4 . The partial sequence(204 bp) of this amplicon was identical (99.5 %) to PSTVdstrain VP87 (LC523667) .Stability of PSTVd in pure culture of P. infestansThe stability of strain VP87 in pure culture of P. infestansisolate PiVZR18v+ after consecutive passages on rye agarwas studied. RT-PCR with primer sets P3/P4 and 68PV/87PV revealed amplification products indicating the presence of PSTVd after the second and thirdpassages on rye agar of P. infestans isolates from viroidinfectedcv. Colomba . PSTVd stability inP. infestans isolates after three passages on rye agar was shownby sequencing of the RT-PCR amplicon with primers P3/P4.The partial sequence of RT-PCR amplicon (near 232 bp) ofviroid in P. infestans isolate PiVZRv+ after the third passageon rye agar received with the primer set P3/P4 is identical(98.3 %) to PSTVd strain VP87 (LC523667). Another partialsequence of RT-PCR amplicon (270 bp) received with theprimer set 68PV/87PV of the same RNA sample is identicalto PSTVd strain VP87 (LC523667) \u2013 99.3 % .On the other hand, PSTVd was not detected after the eighthpassage on rye agar in P. infestans subculture (see the Table).P. infestans isolates infected with viroid strain VP87 werecharacterized by more abundant, but also more compactmycelium, forming an almost felt-like colony .Virulence testing on a set of Black\u2019s potato differentials(11 lines with different resistance genes) of the PSTVd-infected PiVZR18v+ and the initial uninfectedPiVZR18 isolates showed the same types of reactions ondetached leaves of 11 lines after 7 dpi .For both isolates, eight virulence genes were identified. The PSTVd-infected P. infestansisolate seems to be less aggressive in comparison tothe uninfected isolate; however, this observation requiresfurther study.Potato (Solanum tuberosum) is one of the most importantstaple crops worldwide. According to the FAO, over 390 milliontons are produced on over 19 million ha of farmlandworldwide (http://www.fao.org/faostat/en/#data/QCL). Thequarantine status of potato tuber spindle viroids and possiblesignificant losses of potato yield determine the importance ofstudying various aspects of pathogen epidemiology.PSTVd replication is accompanied by the accumulation ofviroid-derived small RNAs (vd-siRNAs) suggested to playa central role in disease symptom developmentPotatoes were domesticated in the Andes in Southern Peruaround 10,000 years ago. Nevertheless, the introduction of thepotato to Europe, along with all its associated diseases, datesback to the 16\u201317th centuries . Late blight ofpotato and tomato is a devastating disease caused by funguslikeoomycete P. infestans. Despite many efforts, the severityof this disease has increased dramatically in recent years.It is known that the mode and speed of spreading plantpathogens are the major factors in the development of epiphytotics.Early studies showed that PSTVd is spread primarilythrough the use of infected plant material produced vegetativelyor as botanical seeds , throughmechanical spreading across the growing crop, particularlybetween plants of different species of the Solanaceae family. Thesuccess of mechanical transmission depends on infected hostplant species or cultivars, as well as the frequency and severityof the disease and the temperature . Importantly, transmission to potato and othertest plants by aphids (Myzus persicae) was successful only ifPSTVd RNA was encapsidated by potato leafroll virus (PLRV)particles .Some viruses are spread by vectors, which can includepathogenic fungi ,oomycetes , and nematodes . Bidirectional transfer betweenFusarium graminearum and tobacco plants of hop stunt viroid(HSVd) during infection was shown by Wei et al. (2019).However, Nicotiana benthamiana is not a natural host foreither HSVd or F. graminearum. Given this fact , more evidence is needed to validate the possibility ofviroid transmission by phytopathogenic fungi. We showed thepresence of PSTVd in P. infestans isolates after colonizationon plants of three potato cultivars infected with viroid. Afterthree passages on rye agar (30 days each), RT-PCR analysisshowed the presence of viroid in pure cultures of P. infestans.The partial RT-PCR amplicon sequence of viroid in P. infestansisolate PiVZRv+ after the third passage on rye agar isidentical (98.3\u201399.3 %) to PSTVd strain VP87 that was usedfor the initial inoculation.Sixty days after inoculation of healthy tomato plantswith P. infestans isolate carrying PSTVd, RT-PCR revealeda 360 bp amplification product, indicating successful infectionof the plants. This is the first report of horizontal transfer ofpotato viroid PSTVd between P. infestans and host plants.Moreover, there is evidence that small RNAs can horizontally transfer from microbesto plants and spread silencing information toward the targetedgenes . Small RNAs were also found in fungi and fungal-like Oomycota . In addition, sRNAs of 19\u201340 nt were found fromP. infestans . There are numerous reportsof sRNA cross-transfer between plants and pathogens . sRNAs can be transportedwithin an organism through the inner side of the plasmamembrane (symplast), or cell wall (apoplast) . It is suggested that sRNAs are translocated by extracellularvesicles (EVs) from Arabidopsis to P. capsica and B. cinerea . Furthermore,it is possible that interaction between oomycete and potatoinvolves not only sRNA exchange but also the movementof larger viroid RNA molecules from mycelium into a plantand vice versa.PSTVd replicates in the nucleus, traffics long distancesin the phloem, and moves cell-to-cell via plasmodesmatain plants . After the third subculture,PSTVd was detected from P. infestans, suggesting that PSTVdcan replicate in the nucleus and locate to non-septate hypha\u0435of P. infestans (see the Table). On the other hand, after theeighth subculture, PSTVd accumulation in P. infestans wasnot detected by RT-PCR. The same results were obtained byWei et al. (2019), in which PSTVd was eliminated from Cryphonectriaparasitica, Valsa mali, and Fusarium graminearumafter eight subcultures. This disappearance could be causedby a defense mechanism against viroid, namely, the RNAsilencing system. Viroids are the target of the RNA silencingsystem and become elicitors of the host defense system viaRNA silencing . Thus,PSTVd could have been degraded by the silencing system,resulting in the elimination of PSTVd from P. infestansPhytophthora infestans produce sporangia on the surfaceof potato leaves, and then zoospores, released from sporangia,form walled cysts on the plant surface . The cysts germinate and extend a germ tube into theleaves and stems of the host plants. PSTVd transferred fromP. infestans to plants, suggesting that PSTVd was present notonly in mycelium but also in sporangia and zoospores. Maturesporangia were dispersed by wind or water . Thus, there is a possibility that PSTVd can spreadlong distances via infected sporangia. In contrast, there is stillno evidence of viroid infection in isolates of P. infestans fromfield populations and the possibility of viroid stability in themycelium of P. infestans in tubers is unclear.Concerning mycoviruses, there are two hypotheses oftheir origin: the first states that they are of an unknown butancient origin and have coevolved along with their hosts,the second one suggests they have relatively recently movedfrom a fungal plant host into fungus .Both hypotheses are also applicable to PSTVd. Prolonged coexistenceof viroid\u2013P. infestans\u2013host plants can lead to viroidtransition from a host plant to an oomycete.Potato spindle tuber viroid is known as autonomouslyreplicating pathogen only of plants and mainly of solanaceouscrops, that lacks any protein-coding sequences. Herein, wedemonstrate the possibility of viroid transmission from hostplants (potato and tomato) to Phytophthora infestans, fromP. infestans to host plants, and the possibility of PSTVd stability in pure cultures of P. infestans after three consecutivepassages on rye agar. These results are initial evidence ofbidirectionally transferred potato viroid PSTVd betweenP. infestans and host plants.The authors declare no conflict of interest.Andika I.B., Weia Sh., Cao Ch., Salaipetha L., Kondo H., Suna L.Phytopathogenic fungus hosts a plant virus: a naturally occurringcross-kingdom viral infection. Proc. Natl. Acad. Sci. USA.2017;114(46):12267-12272. DOI 10.1073/pnas.1714916114.Behjatnia A., Dry I., Krake L., Cond\u00e9 B.D., Connelly M.I., Randles J.,Rezaian M.A. New potato spindle tuber viroid and tomato leafcurl geminivirus strains from a wild Solanum sp. Phytopathology.1996;86:880-886. DOI 10.1094/Phyto-86-880.Bhat Al.I., Rao G.P. Characterization of Plant Viruses. Methods andProtocols. 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Pardy et al. 2021 was cited in the text, however, it was missing from the references. This source has now been added. Drosophila melanogasterandD. simulans. Heredity (Edinb)122, 93-109. PMID:29777168Pardy, J.A., Rundle, H.D., Bernards, M.A., and Moehring, A.J. (2019). The genetic basis of female pheromone differences between"} +{"text": "Albiziacarbonaria Britton as the sister-group of the two currently known species of Pseudosamanea Harms, clearly outside AlbiziasectionArthrosamanea (Britton & Rose) Barneby & J.W. Grimes where it has until now been included. Its morphological similarities to Pseudosamanea are discussed, including characteristics of the polyad, and it is concluded that the species is compatible with the generic description of that genus except for its much more finely divided leaves with smaller leaflets, and its smaller flowers and fruits. Since these are merely quantitative differences, the species can readily be accommodated in Pseudosamanea. The new combination Pseudosamaneacarbonaria (Britton) E.J.M. Koenen is made, and a diagnosis distinguishing it from the other two species of Pseudosamanea is presented.Recent phylogenomic analyses placed Albiziacarbonaria Britton as the sister-group to Pseudosamenea Harms, separate from other Neotropical species of Albizia Durazz. that Arthrosamanea (Britton & Rose) Barneby & J.W. Grimes. Given the finely divided microphyllidious foliage and slender inflorescences of A.carbonaria, with much smaller flowers than those of the macrophyllidious species of Pseudosamanea, this may at first sight seem an unexpected phylogenetic relationship. However, on closer inspection, the similarities between A.carbonaria and Pseudosamanea are immediately apparent Harms Barneby & J.W. Grimes in having more numerous and smaller leaflets smaller relative to Ps.guachapele and cubanaPs .G.P. Lewis 3862), A.carbonaria was previously excluded from Albizia by Albizia to those species with 16-celled polyads. They placed A.carbonaria in Pithecellobium Mart., generating the only homotypic synonym of the species that I am aware of, which is somewhat remarkable for a species of the ingoid clade that was first described nearly a century ago, but all other authors 32-celled polyads now a synonym of Albiziapistaciifolia (Willd.) Barneby & J.W. Grimes, with 16-celled polyads of Albiziaretusa Benth. However, no voucher is cited for the P.daulense polyad in that publication, but in Maguire 56150 which has since been re-identified as Enterolobiumgummiferum J.F. Macbr. in NY . Further reason to doubt that A.pistaciifolia has 32-celled polyads is that in mimosoid species with polyads the fruit is usually pollinated by a single polyad all taxa whose pollen has been studied in the genera Hydrochorea Barneby & J.W. Grimes Barneby & J.W. Grimes, which accordingly appears to have 16(-20?)-celled polyads, see A.carbonaria that has 20\u201326-seeded fruits alld fruits .Pseudosamaneaguachapele has 32-celled polyads . The inflorescences of A.carbonaria appear somewhat similar to those typically found in Albiziasect.Arthrosamanea and many other mimosoid genera where the capitula form a compound inflorescence resembling a pseudo-raceme or a complex panicle of pseudo-racemes with suppression or early shedding of leaves. However, it is questionable whether the description of the inflorescences of Pseudosamanea by S.C. Sant\u2019Ana 1023 and C.E. Hughes 753) have short compound pseudo-racemose inflorescences, comprising multiple umbellate capitula arising from a leaf axil (rather than only singly as described for Ps.guachapele by Pseudosamanea is that the meristem at the apex of reproductive branches continues to grow (i.e. is indeterminate), producing new leaves below which the fruits develop. Unlike in other species of Neotropical Albizia, this is clearly also the case in A.carbonaria, see e.g. E. Suclli & J. Farf\u00e1n 1258 \u2013 NY, Barcode 1300235; J. Leon 4372 \u2013 F, https://collections-botany.fieldmuseum.org/, Catalog number 1578909), providing evidence that the inflorescences of A.carbonaria are not qualitatively different from Pseudosamanea, while being unlike the efoliate pseudoracemes typically found in Albiziasect.Arthrosamanea where the meristem is not continuous.An important character used by A.carbonaria is notable for the dorsally pallid leaflets, the dense golden indumentum of the inflorescence, the distinctly pediceled flowers, and the papery tomentulose pod.\u201d All these characters distinguishing it from other Albiziasect.Arthrosamanea, are in agreement with the generic description of Pseudosamanea E.J.M. Koenencomb.nov.E90DBB00-EE9D-5141-972F-338B7B0E23DCurn:lsid:ipni.org:names:77303801-1Albiziacarbonaria Britton, Sci. Surv. Porto Rico & Virgin Islands 6: 348. 1926. BasionymAlbiziamalacocarpaCalder\u00f3n 2024 ; Williams 952 . Standl. ex Britton & Rose, N. Amer. Fl. 23: 44. 1928. - Types: AlbiziasumatranaKeuchenius s.n. . Steenis, in Encycl. Ned.-Ind. ed. 2, Suppl. Vol. vi. 864. 1931. - Type: Pithecellobiumcarbonarium (Britton) Niezgoda & Nevling, Phytologia 44: 310. 1979.Albiziafilicina Standl. & L.O. Williams ex L. Holdridge & Poveda, Arboles de Costa Rica 1: 134. 1975. nomen nudum.C.L. Bates s.n. .Pseudosamaneacarbonaria can easily be distinguished from the other two currently known species of Pseudosamanea by having 8\u201313 pairs of pinnae and (18\u2013)20\u201330 leaflet pairs, compared to 3\u20136 pairs of pinnae and 5\u20138 leaflet pairs, as well as leaflet size (the larger ones 4.5\u20138 mm long vs. 23\u201350 mm) and flower size 4.4\u20136.4 mm long vs 9.5\u201311 mm in Ps.guachapele and 11\u201313 mm in Ps.cubana; the stamen filaments 13\u201316.5 mm vs. 41\u201345 mm in Ps.guachapele and 25\u201327 mm in Ps.cubana) and fruit size 7\u201312 \u00d7 1.5\u20132.35 cm long (excluding the stipe) vs. c. 12\u201322 \u00d7 2\u20134.5 cm in the other two species. [All measurements taken from Ps.carbonaria: Colombia: G.P. Lewis 3862 , R.T. Pennington 694 , H.P. Fuchs & L. Zanella 22388 ; Peru: A. Daza & T.D. Pennington 16353 , E. Suclli & J. Farf\u00e1n 1258 .Ps.guachapele: Mexico: C.E. Hughes 665 , E.A. P\u00e9rez-Garc\u00eda 1035 ; Honduras: C.E. Hughes & B.T. Styles 117 , C.E. Hughes 753 . Guatemala: D.J. Macqueen 68 , C.E. Hughes 1103 .Pseudosamanea, the following identification key, based on that of Ps.carbonaria, can be used:To identify the species of the genus Pseudosamaneacarbonaria, the genus now comprises three species with native distribution from S Mexico to N Peru and in Cuba , occurring in seasonally dry deciduous forest and gallery forest up to 1000 m (Ps.guachapele), moist upland forest up to 1800 m (Ps.carbonaria), and palm savannas and along watercourses below 50 m (Ps.cubana). Two species, Ps.carbonaria and Ps.guachapele, are cultivated including outside their native range on the Atlantic coast of Brazil, Cameroon (Ps.guachapele) and Indonesia (Ps.carbonaria). While Ps.guachapele is naturally widespread across the range of the genus (except for Cuba), the native range of Ps.carbonaria is not known with certainty, but is presumed to be from Colombia to Panama and Venezuela, and it is introduced as a shade tree in coffee plantations in Central America, the Caribbean, Peru and SE Brazil (With the addition of E Brazil ."} +{"text": "Nature Communications 10.1038/s41467-021-21955-1, published online 19 March 2021.Correction to: The original version of this Article omitted from the author list the 27th author Sara A. Healy, who is from the \u2018Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA\u2019. Consequently, \u2018S.A.H.\u2019 was added to the Author Contributions: \u2018I.S., S.A.H., J.J.T., J.V.R., J.T., J.H., M.B.S., J.R., N.H.T., and P.E.D. supervised the experiments and interpreted the data.\u2019 This has been corrected in both the PDF and HTML versions of the Article."} +{"text": "Bacillus anthracis is the anthrax causative agent. For its epidemiology, it is important not only to identify the etiological agent but also to determine the patterns of its evolution and spread. Modern methods of molecular biology make it possible to detect a number of genetic markers suitable for indicating and differentiating the strains of B. anthracis, including the loci arranged as variable number tandem repeats (VNTRs) and SNPs, one nucleotide-sized differences in the DNA sequence of the loci being compared. The objective of the present study was to examine the effectiveness of SNP analysis and PCR amplif ication of VNTR loci combined with the high-resolution amplicon melting analysis for identif ication and differentiation of the anthrax agent strains. In the study, seven strains of B. anthracis obtained from soil samples and animal carcasses were investigated using vaccine strain STI-1 as a reference. For molecular genetic characterization of these bacteria, analysis of 12 SNPs and variability analysis of eight VNTR loci were carried out. To detect the differences between the strains, their PCR product melting points were measured in the presence of the EvaGreen intercalating dye. For SNP detection, a PCR assay with double TaqMan probes was applied. It was found that the studied virulent strains, except for B. anthracis No. 1 and 3, could not be attributed to any phylogenetic subgroup of the anthrax agents. The proposed method made it possible to differentiate four out of the seven investigated strains. Strains No. 5\u20137 had identical SNP and HRM prof iles and, as a result, formed a single cluster. Our investigation has conf irmed that the proposed method can be successfully used for preliminary analysis of an epizootic situation in the case of anthrax. Bacillus anthracis is the causative agent of anthrax, a particularlyhazardous zoonotic infection. Although effectivemeasures to prevent the occurrence and spread of the diseasehave been developed and rather widely implemented, from2000 to 20,000 anthrax cases are registered around the worldevery year , mostly in Africa, CentralAsia, and Latin America . In Russia, anthrax commonly occurs inSiberia and North Caucasus .All the B. anthracis populations known to researchers areextremely monomorphic and have clonal structure . This high genetic similarity posesa significant hindrance for strain differentiation of anthraxagents using bacteriological and serological methods. Theproblem, however, may be solved using molecular geneticapproaches. The methods detecting sites with variable numbertandem repeats (VNTR) and single nucleotide polymorphisms(SNP) in the agent\u2019s genome have turned out to be the mostpromising for B. anthracis strain indication and differentiation.Compared to VNTR loci, SNPs are more stable in evolutionaryperspective and have low mutation frequency, whichcomes at a cost of lower resolution. That is why polymorphismdetection in SNP loci of the anthrax agent is a rather commonfirst stage in the genotyping systems using a combination ofSNP and VNTR markers , in which aset of 14 diagnostically significant canonical SNPs (canSNPs)is widely used. The systems make it possible to attribute themicroorganism under study to a particular phylogenetic lineand, as a result, make an assumption about its geographicorigin . Three phylogenetic lines are commonly identified in today\u2019s research, whichin turn form 14 phylogenetic groups as follows: A.Br.Ames,A.Br.Australia 94, A.Br.003/004, A.Br.Vollum, A.Br.005/006,A.Br.001/002, A.Br.Western, A.Br.WNA, A.Br.008/009,A.Br.011/009, B.Br.001/002, B.Br.KrugerB, B.Br.CNEVA,and C.Br.A1055 . According to theliterature, the strains isolated in the Russian Federation belongpredominantly to group B.Br.001/002 of line B and groupsA.Br.001/002 and A.Br.008/009 of line A, and less often toA.BrAust94 .Multilocus variable number tandem repeat analysis (MLVA)is used for further strain differentiation within each SNP cluster. PCR analysis with further separationof amplification products in agarose or polyacrylamide gel,often combined with capillary electrophoresis, is the mostcommon MLVA strategy . The mostaccurate results may be obtained from amplicon sequencing,but the duration of the procedure tendsto be a major downside of the approach.In the present study, differences in VNTR loci, specificallytandem repeat numbers, were determined using HRM (highresolution melting), i. e. real-time analysis of amplicon meltingpoints. The EvaGreen intercalating dye usedfor HRM analysis inserts itself between two complementarynucleotides in a double-stranded DNA molecule. The dye\u2019sfluorescence under light of 490-nm wavelength is registeredin FAM detection channel. When DNA denaturation occurs,there is no fluorescence and hydrogen bonds break. Thus, ifwe gradually increase the temperature in the thermocycler,continuous detection will enable us to determine the repeatnumber based on amplicon melting point. The latter approachoutperforms the classical MLVA methods since it does notrequire sequencing or fluorescence-labeled probes, and, as aresult, makes it possible to detect differences in VNTR loci ofB. anthracis strains at a lower financial and time cost. HRManalysis of PCR amplification products had been previouslysuggested for SNP genotyping but hadnever been described for analyzing VNTR loci.The objective of the present study was to evaluate the efficiencyof SNP analysis and PCR amplification of VNTRloci in combination with high-resolution amplicon meltingpoint analysis for identification and differentiation of anthraxagent strains.In the study, seven B. anthracis strains obtained from soilsamples and animal carcasses were used (Table 1). B. anthracisvaccine strain STI-1 from the microorganism strain collectionof the Federal Center for Toxicological, Radiation andBiological Safety was used as a reference.The strain samples were prepared for further molecular geneticresearch in compliance with the MUK 4.2.2941-11 methodologicalprotocol (2011).The genomic DNA was isolated using the DNA-sorb-B kit as per manufacturer\u2019s instructions.The SNP analysis was performed using real-time polymerasechain reaction (qPCR) with the double TaqMan probesand primers described earlier . Themaster mix volume of 15 \u03bcl included 125 \u03bcM of each dNTP,2.5 \u043c\u041c MgCl2, 5 pM of each primer and probe, 10 ng DNAmatrix, 1.0 U Taq polymerase , ddH2O (upto 15 \u03bcl). The qPCR procedure was run on a Real-Time \u04211000thermocycler with CFX96 optical reaction module under the following protocol: initial DNA denaturationat 95 \u00b0C for 3 minutes followed by 39 cycles as follows: denaturation at 95 \u00b0C for 10 s, annealing oligonucleotides at50 \u00b0C for 30 s (detection in R6G/ROX channel), extensionat 72 \u00b0C for 5 s. Point nucleotide changes in each locus wereidentified based on fluorescence intensity in each channel.Variability of SNP loci was numerically estimated based onallelic polymorphism index (h) .MLVA amplicon melting points were determined using theEvaGreen intercalating dye. The primer set for amplificationof VNTR loci is presented in Table 2.The qPCR master mix volume of 15 \u03bcl included 1.5 \u03bcl10 \u00d7 PCR-buffer with the EvaGreen dye (Syntol), 2.5 \u043c\u041c MgCl2solution (Syntol), 1.0 U Taq polymerase (Syntol), 125 \u03bcM ofeach dNTP, 5 pM forward and reverse primers, 10 ng DNAmatrix, ddH2O (up to 15 \u03bcl). DNA amplification with furtherHRM analysis was run on a Real-Time \u04211000 thermocyclerwith CFX96 optical reaction module (Bio-Rad) under the followingprotocol: initial DNA denaturation at 95 \u00b0C for 3 minfollowed by 39 cycles as follows: denaturation at 95 \u00b0C for10 s, annealing oligonucleotides at 60 \u00b0C for 30 s (detectionin FAM channel), extension at 72 \u00b0C for 10 s. Melting parameterswere as follows: temperature range from 65 to 95 \u00b0Cwith 0.2 \u00b0C increments, 5 s dwell time. Melting curves foramplification products were graphically analyzed using CFXManagerTM (Bio-Rad). The amplicons were separated in native8 % polyacrylamide gel (PAAG) .Bioinformation analysis of B. anthracis genomes was performedusing the Vector NTI 9.1 software and NCBI databases(https://www.ncbi.gov).Design and validationMolecular typing of the strains was performed using theextended protocol including the detection of 12 SNP loci referredto as A.Br.001, A.Br.003, A.Br.004, A.Br.006, A.Br.007,A.Br.008, A.Br.009, B.Br.001, B.Br.002, B.Br.003, B.Br.004,and A/B.Br.001 and analysis of eightVNTR loci . The genotyping was validatedusing B. anthracis vaccine strain STI-1.The results of SNP analysis presented in Table 3 allowed usto draw conclusions on the configuration of point nucleotidechanges in the 12 investigated loci of B. anthracis STI-1. Itwas found that, except for two loci (ABr003 and ABr008), the SNP profile obtained matched the data on single nucleotidepolymorphisms available in the literature for the same strain. It should benoted that canSNPs are rather conservative and known for lowmutation rate . Therefore, the validityof atypical single nucleotide changes in loci ABr003 andABr008 detected for B. anthracis STI-1 required furtherconfirmation,particularly by sequencing. Thus, ABr003 andABr008 loci were discarded from the canSNP panel applicablefor strain differentiation at the current research stageMLVA was performed using classical PCR with furtheramplicon separation in PAAG that only allowed us to determinethe approximate sizes of seven investigated VNTR lociof B. anthracis STI-1 as follows: VrrA \u2013 300 bp, VrrB1 \u2013250 bp, VrrB2 \u2013 190 bp, VrrC1 \u2013 700 bp, VrrC2 \u2013 600 bp,CG3 \u2013 160 bp, pX01 \u2013 160 bp. Amplification products for thelocus localized in capsule-encoding plasmid pX02 were notdetected. The absence of plasmid pXO2 is characteristic forB. anthracis STI-1 .The accurate size of the amplified VNTR fragments of theB. anthracis STI-1 DNA as well as nucleotide repeat sizeswere determined in silico. Chromosomal DNA nucleotidesequence of B. anthracis STI-1 (GenBank CP066168) waslimited by the respective primers (see Table 2) using the VectorNTI 9.1 software. The results obtained after bioinformationanalysis of the B. anthracis STI-1 genome are presented inTable 4. The complete nucleotide sequence of plasmid pX01for the investigated strain is not available in the GenBankdatabase. As a result, the tandem repeat number in the locusof interest was determined as a difference between the ampliconmolecular mass and the repeat-free size of the amplifiedfragment divided by the number of nucleotides in the variablesite. Electrophoresis showed that CG3 and pX01 locus sizesfor B. anthracis STI-1 were identical. Thus, to calculate therepeat number for plasmid pX01, the molecular mass of theCG3 locus was used.The melting curve peaks for qPCR amplification productsfor MLVA loci of B. anthracis STI-1 were also identified(see Table 4). The qPCR procedure was performed using theEvaGreen dye in eight replicas. It was found that the differencebetween replicas for most loci under study was 0.2 \u00b0\u0421. Thus,the values of at least 0.2 \u00b0\u0421 were considered an acceptableparameter difference for the further differentiation of anthraxstrains based on VNTR loci melting point differences.Single nucleotide polymorphism analysisThe results of molecular genetic analysis of SNP loci for thestudied virulent strains of B. anthracis are shown in Table 2.It turned out that SNP analysis did not show differences infive loci including A.Br001, A.Br005, A.Br009, B.Br001, A/B.Br001. The values of variability index (h) for the remainingseven SNP loci ranged from 0.12 to 0.4.The results obtained allowed us to divide the investigatedstrains into four clusters. The largest cluster was formed by thethree strains isolated in the Republic of Tatarstan (B. anthracisNo. 6 and 7) in 2008 and 2014 and in Ulyanovsk (B. anthracisNo. 5) in 2004. The second cluster included strains No. 2 and 4collected in the Tajik SSR in 1972 and Ulyanovsk in 2004,respectively. Two remaining clusters were formed by strainsNo. 1 and 3 found in the Checheno-Ingush ASSR in 1971 andin the Kurgan region in 1972, respectivelyThe results of SNP typing allowed us to attribute strainNo. 1 to the phylogenetic subgroup A.Br.003/004. It was foundthat B. anthracis bacteria of strain No. 3 could be attributedto the phylogenetic line A.Br.011/009, similarly to the STI-1reference strain. The SNP profiles obtained for the rest of theinvestigated microorganisms were not characteristic for anyof the previously identified phylogenetic subgroups of B. anthracisstrains.Multilocus variable number tandem repeat analysisThe obtained amplicon melting point values were used toperform VNTR strain differentiation (Table 5). The meltingpoints of the obtained PCR fragments after variable-locusamplification depended on their nucleotide compositions,specifically the tandem repeat numbers, i. e., the higher thelatter, the higher the melting point.It was found that the melting curves of strains No. 1 and 2obtained after amplification in the VrrA1 locus were identicalto the melting curve obtained for the reference strain atthe same locus and probably included four tandem repeats inVrrA1. Four strains (No. 4\u20137) showed higher melting pointscompared to the reference strain, which implies a highertandem repeat number in the VrrA1 locus. On top of that,strain No. 3 showed the lowest melting point in the VrrA1locus among the investigated strains, and as a result it wascharacterized by the lowest repeat number in the VrrA1 locus.Strains No. 5\u20137 and STI-1 showed identical amplicon meltingcurves at VrrB2 and, thus, included three tandem repeatsin the VrrB2 locus, similarly to B. anthracis STI-1. The datafrom Table 5 demonstrate that the rest of the investigatedstrains had lower repeat numbers in this locus, i. e., probablytwo in strains No. 1, 3, 4, 6 and one \u2013 in strain No. 2.The amplicon melting curves in the CG3 locus indicatethat all the strains of interest, except for No. 1, included onetandem repeat, similarly to STI-1, so strain No. 1 probablycarries several repeats in this locus.It was observed that strains No. 2 and 3 were characterizedby amplicon temperatures in pX01 identical to those ofthe reference strain. Thus, a conclusion was made that thesebacteria had 16 tandem repeats in plasmid pX01, whereas theremaining strains had over 16 repeats.The melting points of PCR products obtained after amplificationin loci VrrB1, VrrC1, and VrrC2 were the same forall investigated strains, and, as a result, their repeat numbersfragments were the same in these DNAs as well. STI-1 hadtwo tandem repeats in these loci. The investigated strainsshowed lower amplicon melting points in VrrB1 and VrrC2compared to the reference strain and probably carried one tandemrepeat in these loci. With regards to the VrrC1 locus, themelting points of PCR products obtained after amplificationfor all the investigated strains exceeded the respective valueof the reference strain. Thus, a conclusion can be made thatthe investigated strains carry three or more tandem repeatsin the VrrC1 locus. The number of repeats in the pX02 locuscould not be determined due to the lack of this marker in thereference strain.Thus, it was found that strain No. 1 had a different tandemrepeat number in the CG3 locus, strain No. 2 \u2013 in the VrrB2and pXO2 loci, and strain No. 3 \u2013 in the VrrA1 locus. A uniquemelting point profile of PCR amplification products in VNTRloci was identified for strains No. 1\u20133, making it possibleto differentiate between them. The remaining three strains(No. 5\u20137) showed the same melting point profiles and couldtherefore be combined into one cluster. A similar melting point profile was detected for strain No. 4, its only differencefrom strains No. 5\u20137 being the tandem repeat number in theVrrB2 locus.In recent years, Russian and foreign authors have publisheda substantial number of papers on the design of viable approachesto genotyping anthrax agent strains .Most of the available B. anthracis genotyping methods arebased on polymorphism of tandem repeats or point mutationsin their genome. Some authors believe that the test systemsbased on a combination of genetic markers with different discriminatingpower and stability are the most efficient way todifferentiate between B. anthracis strains . SNP loci are morestable but have a low variability index compared to VNTRones. That is why, when these loci are used in combination,it is recommended to first use canSNPs to attribute the investigatedstrains to a specific phylogenetic group, and then useMLVA to differentiate the strains within each canSNP cluster.PCR amplification followed by visualization of the obtainedamplicons in agarose or polyacrylamide gel is still considereda universal approach to the analysis of VNTR loci . This method may beeffective for differentiation of nucleotide repeats of over 10 bpin size butis not suited for differentiation of repeats of 2\u20133 nucleotidesin size . In our study, the sizes of most repeats did notexceed 10 bp, which made electrophoresis unviable for straindifferentiation, so HRM analysis was applied to differentiatebetween the allelic variants of the VNTR loci based on tandemrepeat numbers. This method is widely used in genotyping,specifically to detect mutations, polymorphisms, and epigeneticdifferences in double-stranded DNA samples . According to the literature,HRM analysis is also applicable for indication and differentiationof Brucella strains According to the literature, the B. anthracis strains circulatingin the Russian territories of high anthrax risk arepredominantly attributed to the A.Br.001/002, A.Br.008/009,B.Br.001/002, and A.BrAust94 genotypes . In particular,the strains isolated in North Caucasus generally fall intocanSNP clusters A.Br.008/009 and A.BrAust94. GenotypeB.Br.001/002 also occurs in the Republic of Dagestan . The strains attributed to phylogenetic groupsA.Br.001/002, A.Br.008/009, and B.Br.001/002 are the mostcommon in Siberia and the Russian Far East .It should be noted that, according to some authors, the varietyof canSNP genotypes is probably not restricted to the 14that are currently described . For example, M.V. Afanas\u2019ev et al. (2014) haveidentified three additional phylogenetic subgroups. Indeed,the results of genetic typing of the seven B. anthracis culturesperformed in the present study using SNP and MLVA analysisshowed that all the studied microorganisms, except for strainsNo. 1 and 3, could not be attributed to the main phylogeneticcanSNP subgroups based on their SNP profiles. Phylogeneticline A.Br.003/004, to which strain No. 1 was attributed, mostlyincludes strains from the American continents . Among all the investigated strains, strain No. 3isolated in the Kurgan region showed the most characteristicSNP profile for Russian isolates.The studied anthrax agent strains are typically organizedinto SNP clusters based on their geographic origin, the exceptionbeing strains No. 2 and 4 isolated in the former Tajik SSRin 1972 and Ulyanovsk in 2004 sharing the same SNP profile.HRM analysis showed that these bacteria had different repeatnumbers in loci VrrA1, VrrA2, pXO1, and pXO2 and, as aresult, may be differentiated from one another. A reasonableassumption would be that these microorganisms had a commongeographic origin but diverged with time affected bytrade and migration flows. According to the literature, VNTRloci are characterized by a high mutation rate (10\u20135 to 10\u20134 pergeneration) and, compared to SNP loci, are in fact the markersof the later evolution of B. anthracis strains.The HRM profiles obtained for the remaining strains ofinterest had the patterns matching well with the SNP profiles.Thus, the extended protocol combining SNP and VNTR analysesmakes it possible to differentiate between four B. anthracisstrains. Strains No. 5\u20137 demonstrated the same SNP and HRM profiles and were therefore combined into the same clusterThe use of HRM analysis has made it possible to differentiatethe strains of interest from one another and attribute themto the respective clusters. We have also determined repeat sizesin the loci, the PCR-product melting points of which wereidentical to amplicon melting points in the same VNTR locifor the reference strain. The state of the art is that the tandemrepeat size may only be accurately determined by sequencing,which means VNTR locus sequencing is to be performed forthe strains of interest in the future. We believe that combiningthe two methods may allow us to create a database of meltingcurves for VNTR loci, in which the curves will be related tothe locus size.Applying HRM to analyze PCR products in VNTR loci hasa high application value. In particular, this approach may beused for a rapid preliminary differentiation of B. anthracisstrains within the same outbreak. 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Genotyping and population diversity ofBacillus anthracis in China based on MLVA and canSNP analysis.Microbiol.Res. 2020;233:126414. DOI 10.1016/j.micres.2020.126414.Winchell J.M., Wolff B.J., Tiller R., Bowen M.D., Hoffmaster A.R.Rapid identification and discrimination of Brucella isolates by use ofreal-time PCR and high-resolution melt analysis. J. Clin. Microbiol.2010;48(3):697-702. DOI 10.1128/JCM.02021-09."} +{"text": "The authors wish to make the following correction to this paper :In the original article, there was a mistake in the method used for heart rate analysis. The correct fragment appears below. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated.On page 6, the last paragraph of 2.4. Hand-Leading Test:The variables were analysed using Kubios HRV software [22], as was described by Tarvainen et al. [23]. For artefact correction in RR analysis, the custom filter of the program was set at the maximal level.should be revised to:The variables were analysed using Polar ProTrainer5 software. No filter level was applied since clear, almost artefact-free RR curves were recorded .22. Kubios HRV Software; version 2.1; Biomedical Signal Analysis Group, Department of Applied Physics, University of Kuopio: Kuopio, Finland, 2012.should be revised to:Physiol. Behav.\u00a02007, 92, 293\u2013316.22. Von Borell, E.; Langbein, J.; Despr\u00e9s, G.; Hansen, S.; Letterier, C.; Marchant-Forde, J.; Marchant-Forde, R.; Minero, M.; Mohr, E.; Prunier, A.; et al. Heart rate variability as a measure of autonomic regulation of cardiac activity for assessing stress and welfare in farm animals\u2014A review. Comput. Methods Programs Biomed.\u00a02014, 113, 210\u2013220, https://doi.org/10.1016/j.cmpb.2013.07.024.23. Tarvainen, M.P.; Niskanen, J.P.; Lipponen, J.A.; Ranta-Aho, P.O.; Karjalainen, P.A. Kubios HRV\u2014Heart rate variability analysis software. should be revised to:Ann. Noninvasive Electrocardiol.\u00a01996, 1, 151\u2013181, https://doi.org/10.1111/j.1542-474X.1996.tb00275.x.23. Malik, M. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use: Task force of the European Society of Cardiology and the North American Society for Pacing and Electrophysiology."} +{"text": "Sci., 2022, https://doi.org/10.1039/d2sc04846a.Correction for \u2018ThC The authors regret that incorrect details were given for ref. 53 and 54 in the original article. The correct version of ref. 53 and 54 is given below.Phys. Rev. Lett., 1996, 77, 3865\u20133868.53. J. P. Perdew, K. Burke and M. Ernzerhof, Phys. Rev. Lett., 1998, 80, 891.54. J. P. Perdew, K. Burke and M. Ernzerhof, The authors also regret that there was an error in the sentence in lines 12\u201313 in the left column on page 5 of the original article. The text originally read, \u201cThe carbon lone pairs are even stronger donating, with 13% weight at thorium.\u201d This sentence should read, \u201cThe carbon lone pairs are even stronger donating, with 14% weight at thorium.\u201dThe Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "The authors would like to make corrections to a recently published paper .In consideration of the contributions to this work, the following authors are removed from the publication: Feng-Ming Lee, Yu-Yu Lin, Chih-Hsiung Lee, Wei-Chen Chen, Che-Kai Shu, and Chih-Yuan Lu. Their support is acknowledged as indicated in the Acknowledgements. The corrected authors are Yi-Yueh Chen, Su-Jien Lin, and Shou-Yi Chang.According to the change in authorship, the corrected affiliation appears below: sjlin@mx.nthu.edu.tw (S.-J.L.); changsy@mx.nthu.edu.tw (S.-Y.C.).Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan; According to the change in authorship, the corrected Author Contributions statement appears below:Conceptualization, Y.-Y.C.; methodology, Y.-Y.C.; formal analysis, Y.-Y.C.; investigation, Y.-Y.C.; resources, Y.-Y.C.; data curation, Y.-Y.C.; writing\u2014original draft, Y.-Y.C. and S.-Y.C.; writing\u2014review & editing, Y.-Y.C. and S.-Y.C.; supervision, S.-J.L. and S.-Y.C.; project administration, Y.-Y.C.; funding acquisition, S.-J.L. All authors have read and agreed to the published version of the manuscript.The corrected Acknowledgments statement appears below:The authors gratefully acknowledge Macronix International Co., Ltd. for their support and technical discussions about this work.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Paediatr Neonatal Pain. (2022) 4:110\u201324. doi: 10.1002/pne2.12071\u201d. It should be \u201cFriederici AD. The brain basis of language processing: from structure to function. Physiol Rev. (2011) 91:1357\u201392. doi: 10.1152/physrev.00006.2011\u201d.In the published article, the reference for [35] was incorrectly written as \u201cJones A, Caes L, Eccleston C, Noel M, Gauntlett-Gilbert J, Jordan A. The sands of time: adolescents' temporal perceptions of peer relationships and autonomy in the context of living with chronic pain. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-022-17184-1, published online 27 July 2022Correction to: In the original version of this Article, Jason T. C. Tzen was omitted as a co-corresponding author. Correspondence and requests for materials should also be addressed to TCTZEN@dragon.nchu.edu.tw.The original Article has been corrected."} +{"text": "After the Black Death: Economy, Society, and the Law in Fourteenth-Century England. The Ford Lectures for 2019. Oxford: Oxford University Press, 2021. Pp. 384. ISBN 9780192599735.Mark Bailey, By Daniel R. CurtisSocial History of Medicine. doi:10.1093/shm/hkab058\u201cDue to a copyediting error, \u201cUK\u201d was erroneously used instead of \u201cEngland\u201d throughout the paper. This has now been corrected online. The publisher apologises for the error\""} +{"text": "Saguinus mystax group. The most geographically broadly distributed and phenotypically diverse species in this group is S. mystax, and its phenotypic diversity has been recognized as three subspecies\u2014S. mystax mystax, S. mystax pileatus and S. mystax pluto\u2014with non-overlapping geographic distributions. In this sense, we carried out an extensive field survey in their distribution areas and used a framework of taxonomic hypothesis testing of genomic data combined with an integrative taxonomic decision-making framework to carry out a taxonomic revision of S. mystax. Our tests supported the existence of three lineages/species. The first species corresponds to Saguinus mystax mystax from the left bank of the Juru\u00e1 River, which was raised to the species level, and we also discovered and described animals from the Juru\u00e1\u2013Tef\u00e9 interfluve previously attributed to S. mystax mystax as a new species. The subspecies S. m. pileatus and S. m. pluto are recognized as a single species, under a new nomenclatural combination. However, given their phenotypic distinction and allopatric distribution, they potentially are a manifestation of an early stage of speciation, and therefore we maintain their subspecific designations.Although the Amazon has the greatest diversity of primates, there are still taxonomic uncertainties for many taxa, such as the species of the Leontopithecus Lesson, 1840, Callimico Miranda-Ribeiro, 1911, Saguinus Hoffmannsegg, 1807, Cebuella Gray, 1866, Callithrix Erxleben, 1777, Leontocebus Wagner, 1839, Mico Lesson, 1840, and CallibellaMarmosets and tamarins\u2014species of the family Callitrichidae , 2016\u2014arSaguinus are distributed in forests of South and Central America , Saguinus niger , Saguinus ursulus Hoffmannsegg, 1807; the bicolor group: Saguinus bicolor , Saguinus martinsi martinsi , Saguinus martinsi ochraceus Hershkovitz, 1966; the oedipus group: Saguinus oedipus , Saguinus geoffroyi , and Saguinus leucopus ; and the mystax group: Saguinus mystax mystax , Saguinus mystax pileatus , Saguinus mystax pluto , Saguinus labiatus labiatus , Saguinus labiatus thomasi , Saguinus labiatus rufiventer , Saguinus imperator imperator , Saguinus imperator subgrisescens , and Saguinus inustus .Tamarins of the genus America ; Fig. 1.s groups : the midbicolor, midas and oedipus groups have been subject to taxonomic revisions , Resolution 301 .S. m. mystax, S. m. pluto, S. m. pileatus, and Saguinus sp. Chromogenetic fields are defined as consistently distinct areas of the body identifiable by hair color and color patterns of the coat . We generated data for 25 specimens of the Saguinus mystax species, including representatives of all described subspecies and spanning the known geographic distribution of the taxa within Brazil. We also generated data for three specimens of Saguinus inustus, an outgroup taxon. We used the SdaI and Csp6I restriction enzymes , and size selected fragments in the range of 320\u2013400 bp using PippinPrep . Samples were sequenced on the IonTorrent PGM using the manufacturer\u2019s recommended protocol.We extracted DNA from tissues deposited at INPA, IDSM, and the Universidade Federal do Amazonas (UFAM). We extracted whole genomic DNA from tissue samples using the standard phenol-chloroform extraction protocol . We thende novo assembly, we used a minimum coverage of 6x per locus, assembling all fragments in the 300\u2013400 bp range. Nucleotides with PHRED scores <30 were excluded, and loci with more than six low quality nucleotides were excluded. Subsequently we clustered alleles within loci and loci across individuals, both at a minimum of 88% similarity. Finally, we generated the final dataset by filtering the clusters such that all loci with more than 50% heterozygotes were excluded-likely paralogs, and the locus had to have been present in at least 19 of the 28 specimens. The resulting dataset contained 556 loci and 196,771 nucleotides. We subsequently statistically reduced the 556 loci into 163 partitions using PartitionFinder2 was filtered to retain all loci with 2\u20135 SNPs per locus following We also processed our raw reads using DiscoSnp-RAD , which uAn initial population structure analysis was performed using fineRADstructure Fig. S2Fig. S2. We used ASTRAL-III for phylSaguinus inustus were used as outgroup. We opted to use both methods since although both are fully coalescent methods of phylogenetic reconstruction, they have slightly different premises and use data in a different form (sequences vs SNPs).We also estimated a phylogeny using SVDquartets implemenS. m. mystax, S. m. pileatus, S. m. pluto and Saguinus sp. The taxonomic hypotheses were: (1) one species\u2014(S. m. mystax + S. m. pileatus + S. m. pluto + Saguinus sp.); (2) two species\u2014; (3) three species\u2014; (4) three species\u2014; (5) four species\u2014. Marginal probabilities of the competing taxonomic hypotheses were then compared by Bayes factors was strongly rejected (BF = 100.92), as was the three species hypothesis compatible with current subspecific classification (BF = 116.64). All other taxonomic hypotheses were strongly rejected as well Common name: Spix\u2019s Mustached TamarinDescription. Head light-black, skin of circumnarial and circumbucal area except at symphysis unpigmented and covered with comparatively long white hairs, whiskers well-developed, remainder of face pigmented or unpigmented and covered with black hairs. Mantle blackish brown with orange subterminal band, terminal band is black, basal one-fourth to one-half of hairs white and showing through irregularly at surface. Arms black, hairs of saddle, rump, and outer side of thighs light black with orange or ochraceus orange subterminal band. Lateral fringe like saddle, but basal portion of hairs drab or withish, and upper surface of hands and feet black. Underparts from middle of lower lip to belly and inner sides of limbs black to blackish brown. The tail is black, except the base that is like the rump. External genitalia mostly or entirely unpigmented and sparsely covered white hairs. We observed tonal variation in saddle, rump and hindlimbs in some individuals of S. mystax. This variation was attributed to individual variation.Type locality: Near S\u00e3o Paulo de Oliven\u00e7a, south bank of the Solim\u00f5es/Amazonas River, Amazonas, Brazil.SynonymsMidas mystax Spix, J.B. von. 1823. Sim. Vespert. Brasil., p. 29. pl. 22.Jacchus labiatus Poeppig, E.F. 1831. Froriep Not. 32: 148.H[apale] mystax Wagner, J.A. 1855. Schreber\u2019s S\u00e4ugth. Suppl. 5: 129.Jacchus mystax Gerrard, 1862. Cat. Bones Brit. Mus., p. 29.M[idas] labiatus Reichenbach, H.G.L. 1862. Vollst. Naturg. Affen, p.11, pl. 3.L[eontocebus] mystax Cabrera, A. 1912. Trab. Mus. Cienc. Nat., Madrid (11): 29.Hapale (Leontocebus) mystax Lampert, H. 1926. Morph Jahrb., 55: 611.Mystax] mystax Pocock, R.I. 1917. Ann. Mag. Nat. Hist., ser. 8, 20: 117. mystax. Hill, W.C.O. 1961. Proc. Zool. Soc. Lond. 137(2): 321.Saguinus mystax Anderson, E.T., Lewis, J.P., Passovoy, M. & Trobaugh, F.E. 1967. Lab. Anim. Care. 17(1): 37.Saguinus mystax mystax Hershkovitz, P. 1968. Evolution 22(3): 563.Saguinus (Tamarinus) mystax mystax Garbino, G.S.T. & Martins-Junior, A.M.G. 2018. Mol. Phylogenet. Evol. 118: 169.Distribution.Saguinus mystax occurs in Peru and Brazil : Brazil: JT021 (IDSM00039), JT025 (IDSM00004), JT027 (IDSM00045), JT052 (IDSM00067), JT055 (IDSM00067), JT084 (IDSM00776), JT094 (IDSM00778), MNFS1027 (INPA), MNFS1532 (INPA), FES98 (IDSM03681), FR210 (INPA), JLP15902 (INPA).Saguinus pileatuspileatus comb. nov.Common name: Red-capped Mustached TamarinDescription. Forehead and crown with broad posteriorly bifurcated reddish orange cap, the color extending forward as a thin line between orbits. Superciliary region, cheeks, temples, and interorbital space black. Hairs of midline of muzzle forming a low crest, black anteriorly, light red posteriorly, the color continuous with that of mid-frontal region. Skin of circumnarial and circumbucal areas except at symphysis unpigmented and covered with comparatively long white hairs forming whiskers, remainder of facial skin more or less pigmented and covered with black hair. Mantle blackish brown with fine light brownish yellow or orange, the basal one-fourth to one-half of the hairs drab to brownish black along midline. Saddle and rump light brownish yellow subterminal band. Dark brown hairs of lateral fringe faintly or not at all banded subterminally, pale brown, drab, or white basally. Outer sides of hindlimbs brown, upper surface of hands and feet is light black. Ventral surface from middle of lower lip to be belly and inner sides of limbs, blackish brown. The tail is black, except the base that is like the rump.Type locality: Lago de Tef\u00e9, near its mouth at Solim\u00f5es/Amazonas River, Amazonas Brazil . Edinburgh Univ. Press, Edinburgh, p. 218.T[amarinus] p[ileatus] juruanus Hill, W.C.O. 1957. Primates. Comp. Anat. Taxon. III. Pithecoidea Platyrrhini . Edinburgh Univ. Press, Edinburgh, p. 235.Saguinus mystax pileatus Hill, W.C.O 1957. Primates. Comp. Anat. Taxon. III. Pithecoidea Platyrrhini . Edinburgh Univ. Press, Edinburgh, p. 235.Saguinus mystax pileatus Hershkovitz, P. 1968. Evolution 22(3): 563.Saguinus pileatus Groves, C.P. 2001. Primate Taxonomy. Smithson. Inst. Press, Washington, DC, p.143.Saguinus (Tamarinus) mystax pileatus. Garbino, G.S.T. & Martins-Junior, A.M.G. 2018. Mol. Phylogenet. Evol. 118: 169.Distribution.Saguinus pileatus pileatus is endemic to Brazil. Its distribution occurs south of the Solim\u00f5es/Amazonas River. The northern portion of its distribution is limited by the Tef\u00e9 River to the west and the Coari River to the east : Brazil: AAM9 (INPA), FR55 (INPA5684), FR68 (INPA5687), FR204 (INPA), MTEFE02 (IDSM03511), MTEFE05 (IDSM03680), TFM01 (IDSM03384), TFM03 (IDSM02229), TFM06 (IDSM03384), TFM09 (IDSM03654), TFM13 (IDSM03657).Saguinus pileatuspluto comb. nov.Common name: White-rumped Mustached TamarinDescription. Head black, skin of circumnarial and circumbucal area except at symphysis unpigmented and covered with hair forming proeminent whiskers, remainder of face covered with black hairs. Mantle black with light brownish yellow, basal portions of hairs drab. Arms black, rump and outer sides of thighs like mantle but with a more even mixture or vermiculation of light black and light brownish yellow. Lateral fringe like back, but hairs drab to grayish basally. Upper surface of the hands and feet black. Underparts from midline of lower lips to anterior part of belly and inner sides of limbs black to blackish brown, lower belly, hairs of inguinal, genital and circumanal region and contiguous portions of the ventral base of the tail is white. Tail is black, except the dorsal portion of the base that is like the rump.Type locality: Brazil: Lago Ayapu\u00e1, Purus River, Amazonas : 1.Tamarin pluto Elliot, D.G. 1913. A Review of the Primates 1: 230.Marikina pluto Hershkovitz, P. 1949. Proc. U. S. Nat. Mus. 98: 413.Marikina (Tamarin) pluto Vieira, C.O.C. 1955. Arq. Zool. S\u00e3o Paulo 8: 396.Tamarinus pluto Hill, W.C.O. 1957. Primates. Comp. Anat. Taxon. III. Pithecoidea Platyrrhini . Edinburgh Univ. Press, Edinburgh, p. 218.Leontocebus (Leontocebus) pluto Cabrera, A. 1958. Rev. Mus. Argentino Cienc. Nat. \u201cBernardino Rivadavia\u201d 4(1): 197.Saguinus mystax pluto Hershkovitz, P. 1968. Evolution 22(3): 563. Also, Groves, C. P. 2001. Primate Taxonomy. Smithson. Inst. Press, Washington, DC, p.143.Saguinus (Tamarinus) mystax pluto Garbino, G.S.T. & Martins-Junior, A.M.G. 2018. Mol. Phylogenet. Evol. 118: 169.Distribution.Saguinus pileatus pluto is endemic to Brazil. It occurs south of the Solim\u00f5es/Amazonas River, from the right bank of the Coari River to the left bank of the Purus River. The southern limit is the Tapau\u00e1 River : Brazil: CTGA-M163 (UFAM), FR226 (INPA), FR228 (INPA).Saguinus kulina sp. n. Lopes, Rohe, Bertuol, Polo, Lima, Valsecchi, Santos, Nash, Silva, Boubli, Farias & Hrbek, 2022.urn:lsid:zoobank.org:act:41E33066-C337-4EA2-AF60-AF75F032E5C.Common name: Kulinas\u2019 tamarin (English), sauim-dos-kulinas (Portuguese), pishi (Kulina).Holotype. IDSM03594, field number BJ015, adult male, skin, skull, skeleton. Specimen collected on July 18th, 2018, in terra firme forest, on the right bank of Andir\u00e1 River, right bank affluent of the Juru\u00e1 River, Juru\u00e1 Municipality, Amazonas State, Brazil.Paratopotype. IDSM03595, field number BJ016, adult female, skin, skull, skeleton. Specimen collected on July 18th, 2018, in terra firme forest, on the right bank of Andir\u00e1 River, right bank affluent of the Juru\u00e1 River, Juru\u00e1 Municipality, Amazonas State, Brazil.Paratypes. IDSM03602, field number BJ023, adult female, skin, skull, skeleton. Specimen collected on July 27th, 2018, in terra firme forest, at Cumaru community, on the left bank of Andir\u00e1 River, right bank affluent of the Juru\u00e1 River, Juru\u00e1 Municipality, Amazonas State, Brazil. IDSM03652, field number TFM07, adult female, skin, skull, skeleton. Specimen collected on August 15th, 2018, in terra firme forest, at Nogueira community, on the left bank of Tef\u00e9 River, Alvar\u00e3es Municipality, Amazonas State, Brazil. IDSM03659, field number TFM15, adult female, skin, skull, skeleton. Specimen collected on July 30th, 2019, in terra firme forest, at Nogueira community, on the left bank of Tef\u00e9 River, Alvar\u00e3es Municipality, Amazonas State, Brazil.Type locality. Reserva Extrativista do Baixo Juru\u00e1 , right bank of Andir\u00e1 River, Amazonas, Brazil.Diagnostic characters . The new species is diagnosable from all other species of Saguinus by mantle and forelimbs light black brown subterminal band yellow, saddle, rump and hindlimbs light black with brown : 29.Hapale (Leontocebus) mystax Lampert, H. 1926. Morph Jahrb., 55: 611.Mystax] mystax Pocock, R. I. 1917. Ann. Mag. Nat. Hist., ser. 8, 20: 117. mystax. Hill, W.C.O. 1961. Proc. Zool. Soc. Lond. 137(2): 321.Saguinus mystax Anderson, E.T., Lewis, J.P., Passovoy, M. & Trobaugh, F.E. 1967. Lab. Anim. Care. 17(1): 37.Saguinus mystax mystax Hershkovitz, P. 1968. Evolution 22(3): 563.Saguinus (Tamarinus) mystax mystax Garbino, G.S.T. & Martins-Junior, A.M.G. 2018. Mol. Phylogenet. Evol. 118: 169.Specimens examined (N = 9): Brazil: BJ015 (IDSM03594), BJ016 (IDSM03595), BJ023 (IDSM03602), FR229 (INPA), FR233 (INPA), FR234 (INPA), FR237 (INPA), TFM07 (IDSM03652), TFM15 (IDSM03659).http://zoobank.org/. The LSID for this publication is: urn:lsid:zoobank.org:pub:64332121-FA59-4102-9487-C586912500FD. The online version of this work is archived and available from the following digital repositories: PeerJ, PubMed Central, and CLOCKSS.The electronic version of this article in portable document format will represent a published work according to the International Commission on Zoological Nomenclature (ICZN), and hence the new name contained in the electronic version is effectively published under that Code from the electronic edition alone. This published work and the nomenclatural acts it contains have been registered in ZooBank, the online registration system for the ICZN. The ZooBank Life Science Identifiers (LSIDs) can be resolved, and the associated information viewed through any standard web browser by appending the LSID to the prefix e.g., via comparisons on the marginal likelihoods of different taxonomic hypotheses. We can ask, for example, what is the likelihood of an observed pattern of evolution\u2014utilizing our knowledge of patterns of intra- and interspecific coalescence embodied in the coalescent theory\u2014given the existence of one taxon vs two taxa. The likelihoods of these two alternate hypotheses can then be compared using the Bayes Factor framework, and the most likely taxonomic hypothesis can be chosen in a non-arbitrary statistically rigorous framework.Recent advances in the collection of genomic data and in the analyses of these data have resulted in renewed interest in taxonomically challenging groups. These advances have resulted in the discovery of new species within not just taxonomically neglected groups, but also of large charismatic mammals such as giraffes and oranSaguinus mystax species. Our analyses overwhelmingly support the existence of three species: Saguinus mystax, Saguinus pileatus, and a third species new to science (Saguinus kulina sp. n.). This taxonomic hypothesis is congruent with phenotypic, phylogenetic and distributional data. In recognition of phenotypic differences and for the purpose of nomenclatorial stability, we also maintain the two subspecies S. p. pileatus and S. p. pluto.Using this conceptual framework, we revised the taxonomy of the Saguinus mystax was a taxonomic complex with one of the largest distributions of any callitrichid primate, designating subspecies to accommodate this taxonomic diversity, and proposing distributional limits of these taxa. Although S. mystax, he did not examine any specimens from the Juru\u00e1\u2013Tef\u00e9 interfluve; this is evidenced by his proposal of occurrence of S. p. pileatus in this area. This is not surprising given that specimens of the Saguinus mystax species were never collected in the Juru\u00e1\u2013Tef\u00e9 interfluve until this study, and therefore could never have been analyzed. Once collected, the inclusion of these specimens resulted in the discovery of a species previously unknown to science.These results in part confirm but also contradict the seminal study of S. p. pileatus and S. p. pluto are not subspecies of S. mystax, but rather a separate species, a result that is partially in agreement with S. p. pileatus should be elevated to a species level since it is phenotypically divergent from S. mystax. Our analyses rejected species-level divergence of the taxa S. p. pileatus and S. p. pluto in favor of one species-level taxon Saguinus pileatus. This taxonomic conclusion is supported by the SVDquartet phylogeny (S. p. pileatus and S. p. pluto are distributed allopatrically and separated by the Coari River, and also differ in pelage color and patterns. These taxa may be at an early stage of speciation, and therefore we recognized this divergence by maintaining these taxa as subspecies of Saguinus pileatus. A better understanding of the evolutionary dynamics and the potential incipient speciation within Saguinus pileatus will require additional sampling and field observations, particularly at the southern end of the geographic distribution of S. p. pluto where, at the headwaters of the Coari River, S. p. pileatus and S. p. pluto are hypothesized to come into geographic contact.Our results also differ in important aspects from hylogeny , it is nhylogeny , howeverSaguinus mystax species group is not the only one in need of taxonomic revision. Much of the taxonomy of Amazonian primates is based on the seminal work of e.g., The Saguinus from the Juru\u00e1\u2013Tef\u00e9 interfluve based on robust genomic evidence, pelage characters and geographic distribution. We also elevate Saguinus mystax to the species level, but we find no conclusive evidence for species level differentiation of Saguinus p. pileatus and Saguinus p. pluto. Finally, we emphasize that field surveys and scientific collection of specimens are essential for the continued advancement of knowledge of primate diversity specifically, and all Amazon biodiversity in general.We describe a new species of 10.7717/peerj.14526/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.14526/supp-2Supplemental Information 2Saguinus mystax, Sk = Saguinus kulina, Sppl = Saguinus pileatus pluto, Sppi = Saguinus pileatus pileatus.Individuals within the same species/subspecies share more coancestry with each other than other species/subspecies, indicated by colors. Sm = Click here for additional data file.10.7717/peerj.14526/supp-3Supplemental Information 3Click here for additional data file."} +{"text": "Dipturus intermedius (Parnell 1837) and the longnose skate Dipturus oxyrinchus (Linnaeus 1758), which have been obtained by Sanger sequencing. We report the length of the sequences to be 16,906 and 16,911\u2009bp, respectively. The length and structure of gene regions, containing 13 protein-coding regions, 22 tRNA genes, two rRNA genes, and two non-coding areas, resemble those of related skate species. Despite D. intermedius being considered a cryptic species with D. batis, the full mitogenomes confirm that D. intermedius and D. oxyrinchus are more genetically similar. In comparison to other Dipturus species, D. intermedius is missing a whole codon in its cytochrome oxidase subunit 2 gene. These mitogenomes will be a useful resource furthering investigation of the population genetic differences and evolutionary history of skate species.We describe the complete mitochondrial genomes of the flapper skate Dipturus batis was shown to be two distinct species, now called the blue skate Dipturus batis (previously D. cf. flossada) and the flapper skate Dipturus intermedius (previously D. batis and D. cf. intermedia) play an important role in fisheries. They make up more than 40% of elasmobranch landings, most from the North Sea and Celtic Sea during a Marine Scotland Science survey under UK Home Office License, and of D. oxyrinchus, Norway during a University of Bergen research cruise, which are now deposited in the Natural History Museum London . No further ethical permissions were required for this study. Species identifications were based on morphological characteristics in Geneious V. 11.1.5 and 16,911\u2009bp in D. oxyrinchus (MT890691), the mitogenomes resembling those of other Dipturus species in size and gene order . Nucleotide frequencies in both species were very similar, with the mitogenome of D. intermedius consisting of 29.9% A, 26.8% C, 14.4% G, and 28.9% T (G\u2009+\u2009C composition of 41.2%) and that of D. oxyrinchus 29.9% A, 26.9% C, 14.5% G, and 28.8% T (G\u2009+\u2009C composition of 41.3%). D. intermedius has the shortest mitochondrial genome among published sequences of Dipturus skates, missing one codon in the cytochrome oxidase subunit 2 gene compared with other species in the genus, while all other genes are of the same length as in other skate species. Phylogenetic reconstruction based on the maximum-likelihood method by RAxML V. 8.2.11 (Stamatakis D. intermedius and D. oxyrinchus as sister taxa (D. intermedius shows a slightly higher pairwise similarity (98.45%) to D. oxyrinchus than to D. batis (96.39%). These new sequences will complement available mitogenomes of batoid species, furthering investigation of population genetic differences and diversity, taxon identification, and phylogenetics of Rajiformes, thereby supporting their conservation.The assembled products produced a consensus sequence of 16,906\u2009bp in ter taxa , confirmter taxa . CorrespTanja N. Schwanck, Aurelien N. Delaval, Leslie R. Noble, Peter J. Wright, David W. Donnan, and Catherine S. Jones contributed to the study conception and design. Primer design, molecular work and analysis were performed by Tanja N. Schwanck under the supervision of Catherine S. Jones. Findings were interpreted and discussed among Tanja N. Schwanck, Aurelien N. Delaval, Leslie R. Noble, Peter J. Wright, David W. Donnan, and Catherine S. Jones. The first draft of the manuscript was written by Tanja N. Schwanck. Aurelien N. Delaval, Leslie R. Noble, Peter J. Wright, David W. Donnan, and Catherine S. Jones commented on previous versions of the manuscript, and together with Tanja N. Schwanck approved the final manuscript and agree to be accountable for all aspects of the work."} +{"text": "The authors wish to make a change to the author names for this paper . Daskala1,*, Pierre-Christian Violet 2, Gustavo Vasquez 1, Katherine Belden 1, Michael Foster 3, Bret Mullin 3, Devon Magee 3, Isabelle Mikell 4, Lokesh Shah 4, Victoria Powers 4, Brian Curcio 5, Daniel Monti 6 and Mark Levine 2,*Dagan Coppock Author Contributions: P.-C.V., D.M. (Daniel Monti) and M.L. conceived the study; D.C., D.M. (Daniel Monti), M.L. and M.F. developed the trial methodology; D.C., G.V., K.B. and B.M. reviewed and enrolled subjects; D.C., D.M. (Daniel Monti), G.V. and K.B. provided clinical oversight and monitored safety; B.M., D.M. (Devon Magee), I.M., L.S. and V.P. were responsible for preparing and curating data; B.C. and D.C. performed formal analyses; D.C. and M.L. prepared the original manuscript draft; all authors reviewed and edited the manuscript; D.M. (Daniel Monti) acquired funding; D.C., D.M. (Daniel Monti) and M.L. supervised overall efforts. All authors have read and agreed to the published version of the manuscript.The \u201cAuthor Contributions\u201d statement thus should be updated to the following version:The second correction was the inclusion of the words \u201cstudy-related\u201d to the sentence: \u201cThere were no reported deaths in either arm.\u201d This sentence has been changed to now read: \u201cThere were no reported study-related deaths in either arm.\u201dThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "Scientific Reports 10.1038/s41598-022-23752-2, published online 15 November 2022Correction to: Martina Sollini and Paola Anna Erba were omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cL.C. conceived the pipeline, set up the case study, analysed the results, prepared the figures, and wrote the manuscript. M.P. formulated and tuned the pruned tree edit distance, provided the mathematical proofs and the simulation study, and wrote the manuscript. A.R. contributed to implement the patient representation pipeline. M.S. segmented the Prostate Cancer lesions and extracted the radiomic features for all patients in the case study. P.A.E collected the data and enrolled the patients in the clinical study. F.I. supervised the analyses and the conception of the pipeline. L.C., M.P., A.R. and F.I. reviewed and approved the manuscript.\u201dThe original Article and accompanying Supplementary Information file have been corrected."} +{"text": "Cissus is the largest genus in Vitaceae and is mainly distributed in the tropics and subtropics. Crassulacean acid metabolism (CAM), a photosynthetic adaptation to the occurrence of succulent leaves or stems, indicates that convergent evolution occurred in response to drought stress during species radiation. Here we provide the chromosomal level assembly of Cissus rotundifolia (an endemic species in Eastern Africa) and a genome-wide comparison with grape to understand genome divergence within an ancient eudicot family. Extensive transcriptome data were produced to illustrate the genetics underpinning C. rotundifolia\u2019s ecological adaption to seasonal aridity. The modern karyotype and smaller genome of C. rotundifolia , which lack further whole-genome duplication, were mainly derived from gross chromosomal rearrangements such as fusions and segmental duplications, and were sculpted by a very recent burst of retrotransposon activity. Bias in local gene amplification contributed to its remarkable functional divergence from grape, and the specific proliferated genes associated with abiotic and biotic responses enabled C. rotundifolia to survive in a hostile environment. Reorganization of existing enzymes of CAM characterized as diurnal expression patterns of relevant genes further confer the ability to thrive in dry savannas. Vitis vinifera). It comprises 16 genera with >950 species and is classified into five tribes . The. TheCissvailable \u201314. Comp . Sp. SpCissuf Cissus . This mabination , 74. Beyichopoda region t7 genes) . Likewisosperms) . Moreove , su, sucis eighttime . AdditioC. rotundifolia genome based on their homologs in Arabidopsis , which plays a vital role in abscisic acid (ABA)-triggered stomatal closure . H. HCissusreferred . Moreovef Cissus , 74. Nevf Cissus , 103.C. rotundifolia are succulent, which exemplifies a convergent evolution with plants from dry habitats, like agave , with minor modifications. Woody plant buffer was used instead of Tris\u2013MgCl2 buffer to isolate the nuclei .About 28.31\u00a0Gb of Illumina reads were used to evaluate the genome size of (v2.2.6) with thee (v2.0) . Flow cye nuclei . Raphanuet al. .The genomes of Database , the Phyal.html) , the Ricsu.edu/) , MaizeGDdb.org/) , and NCBs genome . The lisfrom PGD . All givgov/cdd) and PFAMam.org/) were use C3 leaf and pinepression . On the 2-transformed. Modules were constructed using the following parameters: power \u200a =16, networkType = \u2018signe\u2019, mergeCutHeight = 0.18, corType = \u2018bicor\u2019, minModuleSize =30. All the nine time-point transcripts with three replicates were used to perform cluster analysis with the maSigPro package. The parameters were as following: degree\u2009=\u20093, counts\u2009=\u2009F, MT.adjust\u2009=\u2009\u2018BH\u2019. Transcripts were marked as influential by the T.fit function. Genes with \u2018non-flat\u2019 significantly changed across the nine time points. Nine clusters were displayed using the \u2018see.genes\u2019 function with cluster.method\u2009=\u2009\u2018hclust\u2019, k\u2009=\u20099 in maSigPro. The network of each cluster was constructed by the ARACNE algorithm with \u2018Discovery\u2019 mode and \u2018Na\u00efve Bayes\u2019 mutual information (MI) algorithm type in Cytoscape software. The P-value was calculated based on MI, in which <.05 was selected in each cluster. One percent of genes with at least 10 edges in each network were selected by cytoHubba, and CAM genes also were chosen based on a minimum of 10 directed edges.Transcripts with average FPKM >1 in at least one of the nine samples were used to construct a weighted gene co-expression network by the R package WGCNA. The transcript expression was logC. rotundifolia genome. Of all the promoter sequences, the cis-element enrichment of light, circadian, temperature, and drought in CAM-related and stomatal movement-related promoters were implemented by the FIMO [P-value <.0002 in MEME. Enrichment analysis of about five known cis-elements, including the morning element (CCACAC), the evening element (AAAATATCT), the CCA1-binding site (AAAAATCT), the TCP15 element (NGGNCCCAC), and the G-box element [Promoter sequences in 2\u00a0kb upstream of genes involved in CAM were extracted from the the FIMO program CACGTG) , was per CACGTG) .R. sativus cv. \u2018Saxa\u2019 as the standard for flow cytometry.This work was supported by the National Science Foundation of China (31961143026) and the Scientific Research Program of Sino-Africa Joint Research Center (SAJC201614 and SAJL201607). We would like to thank the Institute of Experimental Botany, Czech Republic, for kindly providing the seeds of C. rotundifolia genome sequencing project. H.P.X., Y.W., Q.Y.L., and T.W. are joint first authors. D.K.G. and Z.F.Z. confirmed the genome size and chromosome numbers with help of B.L. D.K.G. and H.M.Z. isolated DNA. Y.W. and Q.Y.L. carried out the genome assembly, annotation, and transcriptome analysis with the help of J.S.Z. Y.W. carried out the phylogenomic analyses with the help of Y.D.Z., B.L., T.W., and Z.D.C. Y.J.H., Y.S.L., and C.X. detected the diel acid fluctuation in the leaves of C. rotundifolia. Y.S.L., R.J.L, Z.M.L., and Q.Y.L. identified the CAM pathway-related genes. Y.J.H. isolated the total RNAs, and Q.Y.L. performed the expression pattern analysis of CAM pathway related genes with the help of H.S.J. H.P.X., Y.W., Q.Y.L., J.W. and Q.F.W. wrote the initial manuscript. J.W., J.N.W., Z.D.C., Z.C.L., L.M.L., G.W.H., R.J.L., R.A. and R.W.G. contributed to the discussion of project at different stages. All authors revised and contributed to the final version of the text.H.P.X. and Q.F.W. initiated the study of the https://ngdc.cncb.ac.cn/) with the project number PRJCA005006. The final assembled genome and annotation files were also deposited in www.grapeworld.cn/ggh/cis.html. All data is available from the corresponding author upon reasonable request.All data used and generated in this study have been deposited in the National Genomics Data Center (NGDC, The authors declare no competing interests.Horticulture Research online.Web_Material_uhac208Click here for additional data file."} +{"text": "Golding, and William M. Bement. \"Cell healing: Calcium, repair and regeneration.\" Seminars in cell & developmental biology. Vol. 45. Academic Press, 2015. Following publication of the original article , the aut"} +{"text": "The authors regret the inclusion of an error in the above article.The original order of the author list and number of joint first authors was incorrect, published as follows:Xiaomin Xu*, Jiajun Xu*, Chuanwei Li*, Gang Wang*, Wenzhe Wang, Yujian Ye, Yong Chen, Tieqiao Liu, Min Zhao, Xuyi Wang, Na Zhong and Haifeng Jiang*Joint first authorsThe updated author list is as follows:Xiaomin Xu*, Xuyi Wang*, Na Zhong*, Jiajun Xu*, Chuanwei Li*, Gang Wang*, Wenzhe Wang, Yujian Ye, Yong Chen, Tieqiao Liu, Min Zhao and Haifeng Jiang*Joint first authorsThe Author contribution statement has also been amended as follows:X.X., X.W., N.Z., J.X., G.W. and C.L. are co-first authors and contributed equally to writing the manuscript. H.J., N.Z. and X.W. are the principal investigators who conceived the original idea, implemented and analysed the data for the study and X.W., J.X., G.W., C.L. and Y.Y. are co-principal investigators who made contributions to the trial design and implementation. M.Z. and T.L. supervised the study design and data analysis. X.X. and W.W. did the coding for data cleaning and data analysis. Y.C. contributed to the revision of the manuscript and suggestions for data analysis. All authors contributed to the interpretation of the data, and critically reviewed the content and approved the final version for publication.The article has been corrected."} +{"text": "Open Biology13, 220325. (Published online 11 January 2023.) (https://doi.org/10.1098/rsob.220325)The conflict of interest disclosures should have read as follows:Open Biology Editorial Board and is the spouse of Magdalena Zernicka-Goetz. As an author of the above Commentary article, D.M.G. had no involvement in the peer review or editorial decision-making, which was handled by Subject Editor Marek Mlodzik. G.A. declares no conflicts of interest.Conflict of interest declaration. D.M.G. is a member of the This has been corrected on the publisher's website."} +{"text": "Cattle are a reservoir of pathogenic and potentially pathogenic Escherichia coli (E. coli) strains, which can pose a threat to human and animal health. The aim of the study was to evaluate the occurrence of 22 virulence-associated genes (VAGs), as well as the prevalence of antimicrobial drug resistance and three different bla-genes among 49 E. coli strains isolated from healthy cattle. The presence of VAGs that are common among diarrheagenic E. coli (DEC) strains and/or extraintestinal pathogenic E. coli (ExPEC) strains was determined by amplifying specific gene sequences by PCR. The following VAGs associated with DEC were found: east1 in 24.5 % of the studied E. coli strains, estI in 10.2 %, ehxA in 8.2 %, stx2 in 6.1 %, eltA in 4.1 %, estII and stx1 in 2.0 % of the studied strains. The prevalence of ExPEC VAGs was: fimH \u2013 91.8 %, afa/draBC \u2013 61.2 %, iutA \u2013 44.9 %, flu \u2013 32.7 %, sfaDE and hlyF \u2013 30.6 %, iroN \u2013 22.4 %, ompT and papC \u2013 20.4 %, kpsMTII and hlyA \u2013 18.4 %, iss \u2013 14.3 %, usp \u2013 2.0 %, cnf1 and iha were not detected among the studied strains. Based on the found co-occurrence of VAGs \u201cclassical\u201d, hetero-pathogenic and hybrid-pathogenic E. coli strains were found. E. coli strains isolated from cows had a higher diarrheagenic potential, whereas E. coli strains isolated from calves more frequently contained genes associated with the ExPEC pathotype. Among the studied E. coli strains, 77.6 % were resistant to ampicillin, 49.0 % to tetracycline, 20.4 % to chloramphenicol, 16.3 % to cefoperazone, 16.3 % to ceftriaxone, 16.3 % to aztreonam, 14.3 % to cefepime, 10.2 % to norfloxacin, 10.2 % to ciprofloxacin, 6.1 % to levofloxacin and 2.0 % to gentamicin. All strains were sensitive to meropenem and amikacin. 32.7 % of the studied E. coli strains were found to be multidrug resistant, as they were resistant to at least three groups of antibiotics. With PCR, the blaTEM, blaSHV, and blaCTX-M genes were detected in 100, 31.6, and 26.3 %, respectively, of strains resistant to at least one of the beta-lactam antibiotics. Thus, it was shown that the studied faecal E. coli of healthy cows and calves had a high hetero-pathogenic potential, therefore in the future molecular genetic characterization of these bacteria shall be an important part of the epizootic monitoring Representatives of the commensal microbiota, includingEscherichia coli, being obligate residents of the intestinal tractof farm animals, support physiological homeostasis and colonizationresistance of the organism. At the same time, cattle,including healthy animals, present a reservoir of pathogenicand opportunistic E. coli . DiarrheagenicE. coli (DEC) causing outbreaks of intestinal diseases includevarious pathotypes: enteropathogenic E. coli (EPEC), enteroinvasiveE. coli (EIEC), enteroaggregative E. coli (EAEC),enterotoxigenic E. coli (ETEC) and enterohemorrhagic E. coli(EHEC), which include also Shiga toxin-producing E. coli(STEC) .Extraintestinal pathogenic E. coli (ExPEC) are usuallydivided according the infected organ system, e. g. uropathogenicE. coli (UPEC), neonatal meningitis-associated E. coli(NMEC), and sepsis-causing E. coli (SePEC). Intestinal andextraintestinal E. coli strains circulating in agricultural enterprisescan pose a significant health risk to animals and humans.Due to horizontal gene transfer, the E. coli genome is highlyheterogeneous, and strains possessing genes characteristic ofdifferent pathotypes, so called hybrid-pathogenic and heteropathogenicE. coli, are known . Along withthis, the pathogenic potential of intestinal E. coli is formed,which become sources of virulence-associated genes (VAGs)for other microorganisms, or, subsequently, themselves causeintestinal or extraintestinal infections .The widespread use of antibiotics in agriculture leads tothe formation of E. coli strains with a multidrug resistance(MDR) phenotype . The relationshipbetween pathogenicity determinants and antimicrobial resistancecontroversial: in a number of studies, a correlationbetween phenotypic antibiotic resistance and the presence ofcertain VAGs was revealed , in other studies this relationship was absent. In Russia, studies on the occurrence ofhybrid-pathogenic and hetero-pathogenic strains of E. colicirculating among healthy animals of agricultural enterpriseshave not been conducted. In this regard, the analysis of thegenetic profiles of pathogenicity and antibiotic resistance ofE. coli strains, obligate representatives of the intestinal microbiotaof cattle, is important in relation to both epizootic andepidemiological control of colibacillosis in livestock farms.The aim of the study was to evaluate the occurrence of 22VAGs, as well as the prevalence of antibiotic resistance andthree different types of bla-genes among E. coli strains isolatedfrom faeces of healthy cattle.Studied strains. In the study, 49 different strains of E. coli,isolated in 2019\u20132021 at agricultural enterprises (n = 3) andprivate farms (n = 5) in Perm Krai from the faeces of cows(n = 31) and calves from 3 to 13 days of age (n = 18) wereincluded. The strains were obtained from different animalsof the Holstein black-and-white breed. The agricultural enterprisesLLC \u201c\u041arasava\u201d, LLC \u201cSerginskoe\u201d and LLC \u201cRus\u201dspecialize in dairy cattle breeding and raw milk production.The economic diet of feeding and the conditions of keepinganimals (loose method) are the same and typical for theseenterprises.Detection of virulence-associated genes. To obtain matrixDNA for PCR amplification, a loop of bacterial biomass wasresuspended into 100 \u03bcL of ultrapure water, heated for 15min at 97 \u00b0C in a solid-state thermostat with a timer \u0422\u0422-2\u201cTermite\u201d (Russia), centrifuged for 5 min at 13,000 rpm.The supernatants were transferred to fresh Eppendorf tubesand stored at \u201320 \u00b0C until usage. Twenty-two genes encodingeither toxins , adhesins , protectins , proteins of iron uptakesystems or the UPEC-specific protein (usp)were detected by PCR. Primers andprograms according to the recommendations of the authors wereused. Amplifications were carried out in PCR mixtures withTaq-polymerase (LLC \u201cSintol\u201d) in a thermal cycler DNAEngine Dyad Thermal Cycler . Band visualizationand data documentation were performed using a geldocumentation system Gel-DocXR (Bio-Rad).Antimicrobial susceptibility testing. The determination ofthe sensitivity of E. coli strains to antibiotics was carried out inaccordance with the methodical instructions MUK 4.2.1890-04 and the clinical guidelines \u201cDetermination ofthe Sensitivity of Microorganisms to Antimicrobial Drugs\u201d of the Interregional Association for Clinical Microbiology andAntimicrobial Chemotherapy .The strains were tested by the disk-diffusion method usingMuller\u2013Hinton agar and disks for sensitivity to penicillins, cephalosporins , carbapenems , monobactams , aminoglycosides, fluoroquinolones,tetracyclines , phenicols . Resistance of E. coli strains to at least one drug ofthree or more groups of antibiotics was defined as multidrugresistance .Identification of beta-lactamase genes. Detection of genesencoding TEM, SHV, and CTX-M beta-lactamase types wascarried out with PCR using primers and amplification modes,according to the recommendations of the authors with the same PCR mixturesand machines as stated above for detection of virulenceassociatedgenesStatistical analysis. Qualitative features were comparedusing \u03c72 (with Yates correction) or Fisher\u2019s exact test. Dataprocessing was carried out using computer programs MicrosoftOffice XP Excel and Statistica 10.0.Molecular characteristics of the E. coli strainsEvaluation of the prevalence of genes associated with DEC and ExPEC showed that they occurred with different frequencies.The iha and cnf1 genes were not detected (Table 1).All strains contained at least one VAG. The most E. coli wereharbouring three (20.4 %), four (14.3 %), five (20.4 %) andsix (16.3 %) genes, while the proportion of E. coli havingseven or more genes did not exceed 10 %. In total, forty-fivevariants of VAGs combinations were identified.Prevalence of genes associated with DEC pathogenicity.Seventeen strains (34.7 %) contained genes associated withDEC pathotypes. Among the toxin-coding genes, the mostcommon was the enteroaggregative thermostable enterotoxineast1 gene (24.5 %), which is usually, but not exclusively,associated with EAEC. Seven strains (14.3 %) carried genesassociated with ETEC , four cultures containedSTEC-marker genes stx1 (2.0 %) and stx2 (6.1 %).In four cases, ehxA was found, encoding enterohemolysin,which is the main virulence factor of EHEC, but also occursamong other diarrheal E. coli pathotypes .A hetero-pathogenic strain that simultaneously containsmarker genes for STEC and ETEC pathotypes was found.It should be noted that the east1 gene was detected in someE. coli strains identified as STEC and ETEC. The distributionof determinants associated with DEC pathotypes in the studiedE. coli population is shown in Fig. 1.Prevalence of genes associated with ExPEC pathogenicity.The fimH gene was the most abundant (91.8 %). The secondmost common gene was the afimbrial adhesin afa/draBC(61.2 %); also quite often iutA was detected (44.9 %). The pre-valence of the papC, sfaDE, flu, hlyA, hlyF, ompT, kpsMTII,iss, iroN genes varied from 14.3 to 32.7 %. Only in one casethe usp gene was detected.More than half of the strains (55.1 %) corresponded tothe ExPEC group according to the classification criteria ofJ.R. Johnson and T.A. Russo (2005); that is, they containedtwo or more of the following genes: papC, sfaDE, afa/draBC,kpsMII, iutA. Interestingly, eight strains included at leastthree of the five genes that wereproposed by T.J. Johnson et al. (2008) to determine the APECpathotype associated with systemic avian colibacillosis. Onestrain had a high uropathogenic potential because it containedthe usp gene, as well as the hlyA, papC, sfaDE, afa/draBCgenes often found among UPEC strains.Based on the detected combinations of genes, not only\u201cclassic\u201d but also hybrid-pathogenic strains were identified.Eleven (22.5 %) cultures were identified that met the ExPECcriterion and included genes associated with DEC pathotypes. Among them, hybrid pathotypesExPEC/STEC and ExPEC/ETEC were found, but the prevalenceof such strains did not exceed 4.1 %. The ratio of genesassociated with ExPEC and DEC detected in the studied E. colipopulation is shown in Fig. 2.Comparison of the prevalence of VAGs in subpopulationsof E. coli isolated from cows and calves. Some statisticaldifferences in the prevalence of VAGs between E. colifrom samples of cows and calves were found (see Table 1).The iss gene was detected only among E. coli isolated fromcalves, while the stx1, stx2, ehxA, estII, hlyA and usp geneswere found exclusively in E. coli isolated from cows. TheompT gene was found significantly more often in E. coli circulatingamong calves (p = 0.03), while the prevalence of theafa/draBC (p = 0.03) and iroN (p = 0.04) genes was higherin subpopulations of E. coli isolated from cows. In addition,the fimH, papC, sfaDE, estI, east1, kpsMTII genes were morecommon among the latter, but the difference was not statisticallysignificant .Characterization of antimicrobialresistance of E. coli strainsThe proportion of strains sensitive to all studied antibioticswas 12.2 %. E. coli strains resistant to only one drug werethe most common in the population (36.7 %). Cultures weremore often resistant to ampicillin (77.6 %) and tetracycline(49.0 %) (Table 2). It should be noted that all strains weresensitive to meropenem and amikacin.Sixteen strains (32.7 %) had an MDR phenotype, whilethree strains were resistant to at least one antimicrobial agentfrom five or more groups of antibiotics. Of the fourteen identifiedphenotypic profiles of antibiotic resistance, seven wereunique (not repeated more than once). The most common werestrains with the phenotype of resistance to ampicillin (32.7 %),ampicillin and tetracycline (12.3 %), as well as ampicillin,tetracycline and chloramphenicol (10.2 %).Prevalence of beta-lactam resistance genes. Thirty-eightE. coli strains (77.6 %) were resistant to at least one betalactamantibiotic. These strains were tested for the presenceof beta-lactamase genes. Specific amplification for blaTEM was detected in 100 % of cases, for blaSHV \u2013 31.6 %, forblaCTX-M \u2013 26.3 %.Comparative analysis of the prevalence of drug resistancein subpopulations of E. coli isolated from cows andcalves. It should be noted that strains resistant to gentamicinand norfloxacin were found only among E. coli obtainedfrom calves. In the same group, the occurrence of E. colirepresentatives that were not sensitive to tetracycline andchloramphenicol, as well as those with the MDR phenotype,was significantly higher (p < 0.01). The proportion of strainsresistant to other antimicrobial agents was also higher in thecalf group, although the differences were not statisticallysignificant (see Table 2).Relationship between virulence factors and antimicrobialresistanceIn the group of strains with the MDR phenotype, E. coli containingfive or more VAGs were found more often (p = 0.04),and the probability of finding the hlyA, iss, iutA genes in thisgroup was higher than among E. coli without the MDR phenotype(p \u2264 0.05). In the group of strains in which five or morepathogenicity genes were detected, the proportion of E. coliresistant to five or more antimicrobial agents was significantlyhigher (p = 0.04). It should be noted that among E. coli withthe MDR phenotype, there were E. coli containing the markergenes estI, eltA (ETEC), stx1 (STEC), as well as six strainsidentified as APEC.E. coli strains circulating in agricultural settings can pose asignificant risk to human health . On the one hand, the possibility of transmissionof pathogenic E. coli through food products, including cattlemeat, has been revealed . On the otherhand, the presence of similar phylogroups, serotypes andgenetic determinants of pathogenicity in representatives ofE. coli that cause human diseases and E. coli of animal originsuggests that animals can be a reservoir of opportunisticE. coli, as well as pathogens of zoonotic infections . For example, farm animalsare the main natural reservoir and source of STEC strainsthat cause hemorrhagic colitis in humans .The presence of certain virulence factors in the pathogencauses the manifestation of clinical symptoms of intestinaland extraintestinal infections caused by E. coli, the correspondingpathological groups \u2013 DEC and ExPEC . According to numerousstudies, these strains can circulate among the microbiota ofhealthy animals that do not have pronounced symptoms ofthe disease, in addition, some VAGs may be present in thegenomes of commensal E. coli . Our studies showed thatE. coli strains isolated from healthy cattle were characterizedby a high level of genetic diversity and contained pathogenicitydeterminants associated with pathotypes DEC and ExPEC.ExPEC strains were the most common, as they were foundin 55.1 % of the studied strains. E. coli containing markergenes of diarrheagenic pathotypes: STEC (in 8.1 % of cases)and ETEC (14.3 %) were also detected. Similar data werepresented in the study by J.A. Orden et al. \u2013 among the strainsobtained from healthy cattle, there were representatives ofSTEC and EPEC with frequencies of 8.7 and 8.2 %, respectively, whereas the prevalence of ETECand STEC representatives isolated from dairy cows in Chinawas only 4.29 and 1.98 % . It shouldbe noted that in our sample, individual VAGs were detectedwith a high frequency . R.V. Pereira et al. (2011)found that the fimH and iutA genes were more prevalentamong E. coli isolated from healthy calves \u2013 in 100 and 86.9 %of cases respectively, while the sfaDE and afa/draBC geneswere found less frequently \u2013 in 4.9 and 1.6 % of cases, respectively.When comparing the prevalence of pathogenicity determinantsin strains circulating among healthy cattle of Russianand Slovenian farms, it was found that faecal E. coli strainsfrom Slovenian cows had a lower virulence potential, since theoccurrence of VAGs was significantly lower: fimH \u2013 65.2 %, hlyA \u2013 9.0 %, stx2, ompT and kpsMT \u2013 3.4 %, usp \u2013 1.1 %,and the sfaDE, iroN, cnf1 genes were not detected at all (datanot shown).Recently, more researchers have noted that VAGs associatedwith either ExPEC or DEC are found among atypicalE. coli pathotypes .Such strains can cause severe infectious diseases in both farmanimals and humans. In 2011, an outbreak of food poisoningwas recorded in Germany, caused by a hetero-pathogenicstrain of E. coli O104 : H4 with a rare combination of VAGs, characteristic of twodifferent groups of diarrheagenic E. coli \u2013 STEC and EAEC. It was reported that hetero-pathogenicstrains can be isolated from animals and food .In our study, strains were found that included the stx1, stx2genes and the gene of enteroaggregative thermostable enterotoxineast1, which is often found in EAEC strains. However, todetermine this pathotype, it is necessary to identify additionaldeterminants, and also to perform phenotypic studies . ExPEC/STEC hybrids are also high-risk pathogensbecause they cause both diarrhoea and extraintestinalinfection. We found hybrid-pathogenic and hetero-pathogenicstrains in 2.0 and 4.1 % of cases, respectively.Our study revealed that the VAG profiles of E. coli strainscirculating among healthy cows and calves had specific differences.The occurrence of VAGs was higher among E. coli isolated from cows; moreover,genes stx1, stx2, ehxA and estII associated with DEC were detectedexclusively in this sample. Interestingly, among E. coliisolated from calves, the genes ompT, hlyF, iutA, iss weredetected more often. Thus, E. coli living in the intestines ofhealthy cows had a high diarrheagenic potential, while ExPECgenes were common in both samples; however, in the groupof calves, E. coli containing genes associated with the APECpathotype were more common. Perhaps these differencesare related to the fact that bacteria of the DEC pathogroupcan persist in the intestines of cows without causing activeinfection, since the \u201cmature\u201d microbiome provides colonizationresistance, while calves are more vulnerable to DEC,which often cause diarrhoea and death of young animals inthe first days of life . In addition,natural immunity formed in previously ill adult animals, aswell as post-vaccination immunity, provide tolerance to mostpathogenic E. coli.Agriculture accounts for up to 70 % of antimicrobial drugconsumption, so productive animals are the main arena for theemergence of bacterial antibiotic resistance and the emergenceof strains with multiple drug resistance . It was shown thatamong E. coli isolates circulating in poultry and agriculturalenterprises, more than half had the MDR phenotype1.1 Zabrovskaya A.V. Epizootological analysis of the spread of antibioticresistantstrains of pathogens of infectious diseases of farm animals in theNorth-Western federal district of the Russian Federation: Doctor Sci. (Vet.)Dissertation. St. Petersburg, 2019. 323 p.Significant differences in the prevalence of antibiotic-resistantmicroorganisms circulating in livestock farms in differentcountries may be due to the peculiarities of animal housingconditions and the use of antimicrobial drugs. This determinesthe expediency of a comparative study of transmission routesand mechanisms of acquiring antibiotic resistance.Beta-lactam antibiotics and tetracycline preparations aremost widely used in veterinary medicine for treatment andprevention of infectious diseases of cattle . Of particular importance is the growingresistance of microorganisms to extended-spectrum cephalosporins(third and fourth generation), as these antibiotics are critically important for medicine2. 2.Antibiotics in Animal Farming. Public Health and Animal Welfare, 2011.According to our study,strains with the MDR phenotype isolated from healthy cowsand calves were found with a high frequency (32.7 %). Inthe study sample, 77.6 % of cultures were resistant to at leastone antimicrobial agent of the beta-lactam group of antibiotics(16.3 % \u2013 to cefoperazone and ceftriaxone), 49.0 % \u2013 totetracycline, and 20.4 % \u2013 to chloramphenicol. These datasignificantly exceed the values published by B.P. Madoshi etal. (2016), who found the proportion of strains isolated fromhealthy cattle and resistant to ampicillin, tetracycline andchloramphenicol was 21.3, 33.1 and 4.4 %, respectively. Only3.7 % of the strains were resistant to cefotaxime . Even lower resistance to cephalosporins (1.5 %)was demonstrated by E. coli strains isolated from cattle faecesat agricultural enterprises in Japan .Beta-lactamase production is one of the main mechanismsof resistance to beta-lactam antibiotics. In the studied strainsresistant to at least one agent from this group of antimicrobialdrugs, genes and combinations of beta-lactamase genes of theTEM, SHV and CTX-M families were found. This fact maybe related to the widespread use of beta-lactam antibiotics inenterprises of Perm Krai. However, it was found that evenamong strains isolated from cattle on farms where antibioticswere rarely used, the occurrence of blaCTX-M ranged from2.3 to 25.0 % . Attention should be paid tothe high occurrence in E. coli strains of genes encoding betalactamases,the plasmid localization of which can contributeto the effective spread of antibiotic resistance within themicrobial population through horizontal transfer.According to our data, in general, resistance to antimicrobialagents was more common in the E. coli subpopulationisolated from calves than among E. coli isolated from adultanimals. The largest differences were observed for tetracycline(94.4 versus 22.6 %) and chloramphenicol . Perhapsthis is due to the addition of these drugs to the calves\u2019 feedfor a long period, since it is known that antibiotics are oftenadded to milk or milk substitutes in order to prevent diseasesand treat diarrhoea, which is the main cause of mortality ofcalves before weaning .It is known that the phenotype of resistance of bacteria circulatingamong calves is mainly a consequence of the use ofantibiotics in enterprises . Antibiotics of the aminoglycoside group \u2013 neomycinand gentamicin, are of great importance for the preventionand treatment of streptococcal and staphylococcal infectionsin calves3. 3 Esaulenko N.N. The effectiveness of the use of the probiotic \u201cSporothermin\u201din the diets for heifers: Cand. Sci. (Agric.) Dissertation. Krasnodar, 2015. 118 p.This may explain that E. coli strains resistant togentamicin and norfloxacin were found only among E. coliderived from calves.Microbiological monitoring of pathogenic and conditionallypathogenic microorganisms isolated from farm animals andfrom animal products is currently carried out at all enterprisesof the Russian Federation. This monitoring is important, as bacteria in the herd can circulate between animals of allages over a long period of time, posing a risk to the animalsthemselves and to the personnel.This paper presents for the first data on the prevalence ofVAGs, as well as the occurrence of hybrid-pathogenic andhetero-pathogenic strains of E. coli circulating among healthyanimals at agricultural enterprises in the European part ofRussia (Perm Krai). In addition, the relationship between thevirulence potential of E. coli and their antibiotic resistance wasanalysed. Another important aspect presented in the work isa comparative analysis of the biological properties of E. colistrains isolated from different age groups of animals \u2013 cowsand calves.Studies have shown that E. coli strains circulating amonghealthy animals on farms and agricultural enterprises werecharacterized by a high hetero-pathogenic potential. In theE. coli population under consideration, representatives ofDEC (including STEC and ETEC), which can cause intestinalinfections, as well as ExPEC, causing extraintestinal infections,were common. In addition, hybrid strains combining genesassociated with different E. coli pathotypes were found. Strainswith the MDR phenotype had a high virulence potential,since they more often contained more than five VAGs. E. coliisolated from cows showed a higher diarrheagenic potential,while E. coli isolated from calves more often contained genesassociated with the ExPEC pathotype. E. coli obtained fromcalves generally showed greater resistance to antimicrobialagents than E. coli isolated from adult animals.The obtained data on the molecular properties of microorganismsof the intestinal microbiota of healthy cattle allowto assess their epizootic significance and can serve as a basisfor the formation of a monitoring system for colibacillosis inagricultural enterprises.The authors declare no conflict of interest.Ahmed A.M., Motoi Y., Sato M., Maruyama A., Watanabe H., FukumotoY., Shimamoto T. Zoo animals as reservoirs of gram-negativebacteria harboring integrons and antimicrobial resistance genes.Appl. Environ. Microbiol. 2007;73(20):6686-6690. DOI 10.1128/AEM.01054-07.Aleisa A.M., Ashgan M.H., Alnasserallah A.A., Mahmoud M.H.,Moussa I.M. Molecular detection of \u03b2-lactamases and aminoglycosideresistance genes among Escherichia coli isolates recoveredfrom medicinal plant. Afr. J. Microbiol. 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The genome-wide basic characteristics of C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris revealed unequal genome size, with C. cicadae as the largest (34.11 Mb), followed by C. militaris (32.27 Mb). However, the total gene lengths of C. pseudotenuipes and C. tenuipes were similar (30.1 Mb and 30.06 Mb). The GC contents of C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris genomes differed slightly (51.40% to 54.11%). AntiSMASH and local BLAST analysis showed that C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris had 31, 28, 31, and 29 putative SM BGCs, respectively. The SM BGCs contained different quantities of polyketide synthetase (PKS), nonribosomal peptide synthetase (NRPS), terpene, hybrid PKS + NRPS, and hybrid NRPS + Other. Moreover, C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris had BGCs for the synthesis of dimethylcoprogen. C. pseudotenuipes, C. tenuipes, and C. cicadae had BGCs for the synthesis of leucinostatin A/B, neosartorin, dimethylcoprogen, wortmanamide A/B, and beauvericin. In addition, the SM BGCs unique to C. pseudotenuipes were clavaric acid, communesin, and deoxynivalenol. Synteny analysis indicated that the scaffolds where the SM BGC was located were divided into more than 70 collinear blocks, and there might be rearrangements. Altogether, these findings improved our understanding of the molecular biology of the genus Cordyceps and will facilitate the discovery of new biologically active SMs from the genus Cordyceps using heterologous expression and gene knockdown methods.The whole genome of Cordyceps pseudotenuipes H. Yu, Q. Y. Dong, and Y. Wang is a new fungal species that was published in April 2022 [C. tenuipes (Peck) Kepler, B. Shrestha, and Spatafora. Taxonomically, this species was related to C. tenuipes and similar groups, including C. cicadae (Miq) Massee and C. militaris Fr. [Cordyceps had many bioactive components, including cordycepin [Trypanosoma evansi [ril 2022 . The spearis Fr. ,2,3. Genrdycepin , cordycerdycepin , alkaloirdycepin , cordycerdycepin , pentostrdycepin , ophicorrdycepin , beauverrdycepin , myriocirdycepin , beauverrdycepin , and oosrdycepin G. Winter [Genome mining is a computational method that automatically detects and annotates biosynthetic gene clusters (BGCs) from genomic data . Today, pathways . Moreove. Winter .C. militaris CM01 revealed a cryptic gene cluster of encoding highly reducing polyketide synthase (HR-PKS), enol reductase (ER), and cytochrome P450. In A. nidulans, heterologous expression of the cryptic gene cluster produced two novel polyketide compounds, cordypyrone A and B [C. militaris CM01\u2019s two strains, 1630 and DSM 1153, Wang et al. identified two NRPS genes, one PKS, and a hybrid cluster. They predicted the structural characteristics of their potential products [C. pseudotenuipes SM, its whole genome was sequenced and analyzed, while its whole genome data were compared with those of C. tenuipes, C. militaris, and C. cicadae, as well as for gene mining studies. The results showed that C. pseudotenuipes, C. tenuipes, C. militaris, and C. cicadae all contained different amounts of BGCs, including PKS, NRPS, terpene synthase (TPS), hybrid PKS + NRPS, and hybrid NRPS + Other.Whole-genome analysis of A and B . From thproducts . In ordeC. tenuipes, C. cicadae, C. militaris, and C. pseudotenuipes strains were collected from Sapa, Vietnam; Dimalo village, Bangdang Township, Gongshan County, Yunnan Province; Zixi mountain, Zixi Town, Chuxiong City, Yunnan Province; and Yeyahu Forest Park, Kunming City, Yunnan Province. The voucher specimens were stored in Yunnan Herbal Herbarium (YHH) of Yunnan University, and the isolated strains were stored in Yunnan Fungal Culture Collection (YFCC) of Yunnan University. The whole-genome data of C. tenuipes were obtained from Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University. The genome-wide data of C. cicadae and C. militaris were obtained from NCBI (https://www.ncbi.nlm.nih.gov/ (accessed on 3 March 2022)), accession numbers ASM296887v1 and GCA_000225605.1, respectively.C. pseudotenuipes was cultured on an MY solid medium at 28 \u00b0C for 10 days. The mycelium was transferred to fresh MY liquid medium at 28 \u00b0C at 150 r/min. After 8 days of culture, mycelia were collected, and three biological replicates of each sample were stored in a refrigerator at \u221280 \u00b0C until they were transported on dry ice to Personalbio for high-throughput sequencing.C. pseudotenuipes gene library with 400 bp insert fragments. Raw data were processed using FastQC, 3\u2032-terminal DNA junction was decontaminated using AdapterRemoval (version 2) [We used the Illumina NovaSeq 2000 platform to construct the rsion 2) , and Soarsion 2) softwareGene prediction was performed using homology, SNAP, and Augustus software. The predicted genes were annotated through BLAST searches against existing databases, including NCBI non-redundant protein sequences (Nr), Swiss prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Evolutionary Genealogy of Genes: Non-supervised Orthologous Groups (EggNOg), Pathogen\u2013Host Interactions Database (PHI), and Carbohydrate-Active Enzymes (CAZy).C. tenuipes, C. cicadae, C. militaris, and C. pseudotenuipes scaffolds were performed using the antiSMASH (https://antismash.secondarymetabolites.org/ (accessed on 27 May 2022)) online program. AntiSMASH detected scaffolds with gene clusters by using C. militaris as a parameter. The FGENESH (www.softberry.com/ (accessed on 28 May 2022)) online program predicted gene structures, and the PKS/NRPS online program (nrps.igs.umaryland.edu/ (accessed on 1 June 2022)) determined the gene clusters in contigs containing genes with NRPS/PKS structural domains. Meanwhile, the BLAST analysis (https://blast.ncbi.nlm.nih.gov/ (accessed on 8 June 2022)) was used for protein structure comparison to identify contigs harboring the NRPS/PKS gene.Gene cluster predictions for http://iqtree.cibiv.univie.ac.at/ (accessed on 25 June 2022)). The analysis involved 1000 bootstraps using default parameters for constructing the cluster tree.Known NRPS, PKS, and hybrid PKS-NRPS protein sequences were downloaded from NCBI and compared with protein sequences from this study using the Clustal W program of the MEGA5.0 software of IQ-TREE. The IQ-TREE web server is fast and accurately generates phylogenetic trees using the maximum likelihood method , yielding 34,001,494 HQ reads. The whole genome of 0.41 Mb . For nonC. pseudotenuipes genes on publicly available protein sequence databases yielded varying results. The NCBI Nr (8596 genes) had 98.75%, Swiss-Prot (6206) had 71.29%, KEGG 3614 had 41.52%, GO (3614 genes) had 41.52%, EggNOg (7877) had 90.49%, Cytochrome P450 (CYP) (8480) had 97.42%, and Transporter Classification Database (TCDB) (1358) had 15.60% similarity to the 8705 predicted proteins , unaffected pathogenicity (970), loss of pathogenicity (208), lethal (123), increased virulence (hypervirulence) (89), effector (plant avirulence determinant) (16), sensitivity to chemical (7), resistance to chemical (5), and enhanced antagonism (2). The results showed that the main annotated genes were for reduced virulence and unaffected pathogenicity, indicating that C. pseudotenuipes was a mildly pathogenic strain.Pathogen and host-interaction database (PHI-base), mainly from fungi-, oomycete-, and bacterial pathogen-infected hosts, included animals, plants, fungi, and insects . Thus, tPHI-base . C. pseuC. pseudotenuipes, including 168 glycoside hydrolases (GHs) and 63 carbohydrate esterases (CEs), 56 auxiliary activities (AAs), 16 carbohydrate-binding modules (CBMs), and 3 polysaccharide lyases (PLs) in es (PLs) . CAZy caC. pseudotenuipes was characterized and compared with its three close taxa (C. cicadae was the largest (34.11 Mb), followed by C. militaris (32.27 Mb), C. pseudotenuipes (30.1 Mb), and C. tenuipes (30.06 Mb). Moreover, C. cicadae had the highest number of scaffolds (595), C. pseudotenuipes and C. cicadae contained an equal number of scaffolds (527), C. tenuipes contained 285 scaffolds, and C. militaris had the lowest scaffold number (32). The genome containing the highest number of contigs was C. cicadae (1799), followed by C. pseudotenuipes (645), C. militaris (597), and C. tenuipes (384). However, the GC contents of C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris were 54.11%, 53.72%, 52.70%, and 51.40%, respectively.The genome of litaris) . C. cicaC. pseudotenuipes and C. cicadae had the same putative SM BGCs (31), followed by C. militaris (29) and C. tenuipes (28) (C. pseudotenuipes NRPSs (16), followed by C. cicadae (15), C. tenuipes (13), and C. militaris (9). C. militaris had six PKS + NRPS hybrids, C. cicadae had five, and both C. pseudotenuipes and C. tenuipes had four. C. tenuipes contained the majority of NRPS + Other hybrids (3), C. cicadae and C. militaris had two, and C. pseudotenuipes had one. C. pseudotenuipes, C. cicadae, C. militaris, and C. tenuipes contained decreasing amounts of encoding TPS. C. pseudotenuipes (1), C. cicadae (1), C. militaris (2), and C. tenuipes (2) had similar numbers of other biosynthetic genes. C. pseudotenuipes, C. tenuipes, and C. cicadae had the same PKSs (5), while C. militaris had the highest number (8). The C. pseudotenuipes genome had five PKSs, including three HR-PKSs, two partially reducing (PR) PKSs, and one non-reducing (NR) PKS. The five PKSs obtained from the C. tenuipes genome included three NR-PKSs, one HR-PKS, and one PR-NRPS. The genome of C. cicadae had five PKSs, including two NR-PKSs, two HR-PKSs and one PR-NRPS. The eight PKSs retrieved from the C. militaris genome included five HR-PKSs, two PR-NRPSs, and one NR-PKS. These results showed that the number and type of SM BGCs obtained differed among species of the same genus.AntiSMASH and local BLAST analyses showed that pes (28) . The SM C. pseudotenuipes having the highest homology (37.93%), followed by C. tenuipes (28.57%) and C. cicadae (25.81%). The BGCs predicted from C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris genomes potentially synthesize dimethylcoprogen. In contrast, the BGCs predicted from C. pseudotenuipes, C. tenuipes, and C. cicadae predicted biosynthesis genes that catalyze the synthesis of leucinostatin A/leucinostatin B, neosartorin, dimethylcoprogen, wortmanamide A/wortmanamide B, and beauvericin. The antiSMASH and local BLAST analyses showed that only C. tenuipes, C. cicadae, and C. militaris potentially produce viriditoxin, while C. tenuipes and C. cicadae potentially produce trichodiene-11-one. Moreover, C. pseudotenuipes, C. cicadae, and C. militaris possibly catalyzed the synthesis of squalestatin S1; C. pseudotenuipes and C. cicadae also had BGCs for ilicicolin H synthesis, while C. pseudotenuipes and C. tenuipes were presumed responsible for epichloenin A synthesis. AntiSMASH analysis showed that ferrichrome was unique to C. cicadae, clavaric acid, communesin, and deoxynivalenol were unique to C. pseudotenuipes, and phomasetin, fumosorinone, and 1-nonadecene/(14z)-1,14-nonadecadiene were unique to C. militaris. Furthermore, similar species of the same genus had different types and quantities of BGCs and catalytically synthesized compounds.The predicted BGCs showed different levels of genetic homology to known clusters in the MIBiG database, with C. pseudotenuipes, C. tenuipes, and C. cicadae were 100% similar to MIBiG sequences. Dimethylcodogen was siderophores, produced by the Alternaria species to obtain extracellular iron [C. militaris, region 71.1 of C. pseudotenuipes, region 56.2 of C. cicadae, and region 18.2 of C. tenuipes might be responsible for dimethylcodogen biosynthesis , PTZ00265 superfamily, and MFS superfamily.Several BGCs of lar iron ,35. The ynthesis a. Regionynthesis b, and reC. pseudotenuipes, C. tenuipes, C. militaris, and C. cicadae were similar to known gene clusters in the MIBiG database (ranging from 40% to 85%). Region 78.1 of C. pseudotenuipes, region 94.1 of C. cicadae, and region 426.1 of C. militaris are for squalestatin S1 synthesis. Region 38.2 of C. tenuipes, region 117.1 of C. cicadae, and region 95.1 of C. militaris probably synthesized viriditoxin, while region 1.2 of C. cicadae and region 346.1 and region 468.1 of C. militaris synthesized ferrichrome, phomasetin, and fumosorinone, respectively. The results showed that C. pseudotenuipes lacked the potential to synthesize viriditoxin and that catalytic synthesis of viriditoxin required several additional enzymes besides the core enzyme PKS (SAT-KS-AT-PT-ACP-ACP-ACP-TE). The additional enzymes included the Abhydrolase superfamily, MFS_Azrl_MDR_like, SDR, AdoMet_Mtases superfamily, and others of unknown function BGCs (GenBank: EU886196.1) . The putC. tenuipes region 36.1, C. cicadae region 27.1, and C. pseudotenuipes region 112.1 resembled wortmanamide A or wortmanamide B BGC -SDR. KS-AT-DH-MT-KR-ACP-C was the domain for catalytic wortmanamide A/B synthesis. The domains also had slightly different modifier genes. For instance, the modifier genes downstream of C. tenuipes region 36.1 was reductase, not enoyl_reductase, and thiolase, instead of thioesterase for C. tenuipes region 36.1, C. cicadae region 27.1, and C. pseudotenuipes region 112.1. Thus, C. tenuipes region 36.1, C. cicadae region 27.1, and C. pseudotenuipes region 112.1 might synthesize wortmanamide or its analogs.Furthermore, the gene clusters of de B BGC . WortmanCordyceps PKS and hybrid PKS-NRPS proteins with other fungal PKS and hybrid PKS-NRPS proteins showed that C. militaris region 346.1 clustered with Pyrenochaetopsis sp. (BBC43184.1), which catalyzed phomasetin biosynthesis . Moreover, C. militaris region 95.1, C. cicadae region 117.1, and C. tenuipes region 38.2 possibly catalyze viriditoxin or its analogs. C. pseudotenuipes region 112.1, C. cicadae region 27.1, C. tenuipes region 36.1, and Talaromyces wortmannii (QBC19710.1) were clustered on an independent branch that produced wortmanamide A/B. C. pseudotenuipes region 112.1, C. cicadae region 27.1, and C. tenuipes region 36.1 presumably catalyze the synthesis of wortmanamide A/B or its analogs. C. militaris region 468.1 clustered with C. fumosorosea (AKC54422.1), which catalyzed fumosorinone biosynthesis. Furthermore, C. militaris region 468.1 might catalyze the biosynthesis of fumosorinone or its analogs. C. pseudotenuipes region 71.1, C. cicadae region 56.2, and C. tenuipes region 18.2 clustered with Alternaric alternata (AFN69082.1) catalyzed dimethylcoprogen synthesis , which catalyzed BEA biosynthesis, and the three regions presumably catalyze the biosynthesis of BEA or its analogs. Likewise, C. pseudotenuipes region 111.1 and C. tenuipes region 34.1 clustered on an independent branch with Epichloe festucae (AET13875.1), an E. festucae protein sequence that catalyzed epichloenin A biosynthesis. We hypothesized that C. pseudotenuipes region 111.1 and C. tenuipes region 34.1 might catalyze the synthesis of epichloenin A or its analogs.C. cicadae (24), C. militaris (26), C. pseudotenuipes (27), and C. tenuipes (28) were subjected to synteny analysis. The scaffolds where the SM BGC were located were divided into more than 70 collinear blocks, and there may be rearrangements using the antiSMASH online tool and 27 clusters of SM biosynthesis genes, including 7 NRPS, 7 hybrid PKS-NRPS, 5 PKS, 4 terpenoid cyclase (TC), and 4 others [C. militaris genome that catalyzed beauveriolide synthesis using NRPS, PKS, acyltransferase, and ATP-dependent long-chain fatty acyl-coenzymes A synthase [C. militaris regions 67.1 and 67.2 and between 67.1 and 67.2 were consistent with the gene cluster catalyzing the synthesis of the identified beauveriolide. C. militaris region 536.1 and its four downstream modifier genes were consistent with the gene clusters that catalyzed the synthesis of two novel polyketide compounds, cordypyrone A and B. [C. tenuipes region 36.1, C. cicadae region 27.1, and C. pseudotenuipes region 112.1 might catalyze the synthesis of wortmanamide or its analogs [C. cicadae potentially catalyzed the synthesis of BEA or its analogs, confirming previous studies where BEA was isolable from C. cicadae [C. cicadae region 87.1 and its modifier genes were BGCs that catalyze BEA biosynthesis.Fungal SMs were generally classified based on their building blocks into polyketides (PKs), such as lovastatin, nonribosomal polypeptides (NRPs), such as penicillin, and terpenes, such as gibberellin . Nonriboilitaris . In this4 others . The consynthase . However cicadae . Thus, tA. flavus [A. nidulans, indicating that a rational redesign of fungal natural product enzymes was feasible [Aspergilli [Magnaporthe oryzae [A. terreus through genome mining [C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris genomes analyzed in this study showed that the type and number of putative BGCs differ among species of the same genus. C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris contained 4, 4, 5, and 6 hybrid PKS-NRPS, respectively. Thus, gene chimerism probably occurred in the PKS and NRPS of genus Cordyceps and catalyzed the synthesis of chimeric compounds. The antiSMASH and local BLAST results showed that horizontal gene transfer possibly occurs among these species of the same genus, explaining the variable direction and position of gene sequences. The next step is to validate the SM BGCs of C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris through heterologous expression or gene knockdown.Moreover, NRPS and PKS also appeared to hybridize PKS-NRPS or NRPS-PKS when catalyzing the synthesis of compounds. Chimeric genes produced chimeric compounds and biologically active hybrid products such as cyclopiazonic acid, pyranonigrin, and cytochalasin ,43,44,45. flavus . Moreovefeasible . Theobale oryzae . Tang ete mining . Sigriste mining . In thatC. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris genome showed that the collinearity of C. militaris sequences was significantly different from that of C. pseudotenuipes, C. tenuipes, and C. cicadae. It was presumed that the classification of C. militaris was far from that of C. pseudotenuipes, C. tenuipes, and C. cicadae.The synteny analysis of scaffolds containing SM BGC In Cordyceps, the whole genome of C. pseudotenuipes was sequenced, annotated, and compared with three related species to characterize the genome. The high-quality whole-genome sequence of C. pseudotenuipes was obtained and extensively analyzed by gene prediction and annotation in this work. The results demonstrated that C. pseudotenuipes harbored abundant functional genes in regulatory protein bioactivity and conversion, signal transduction and metabolism, carbohydrate transport and metabolism, capturing energy, and decomposes carbohydrates.In order to deeply explore the SMs BGCs of the genus C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris revealed unequal genome sizes and GC contents. AntiSMASH and local BLAST analyses showed that C. pseudotenuipes, C. tenuipes, C. cicadae, and C. militaris had different amounts and types of putative SM BGC. Presumably, only seven of the putative BGCS were highly similar to known gene clusters, indicating a great potential to generate other SMs. These findings opened the possibility of targeted genomic mining, such as gene knockdown, introduction or heterologous expression of microbial genes, promoter regulation, and mutation induction, to awaken the silenced BGC biosynthesis of more novel bioactive SMs for new drug research and development.The genome-wide basic characteristics of"} +{"text": "Trypanosoma species. The endosymbiont Sodalis glossinidius is suggested to play a role in facilitating the susceptibility of tsetse flies to trypanosome infections. Therefore, this study was aimed at determining the prevalence of S. glossinidius and trypanosomes circulating in tsetse flies and checking whether an association exists between trypanosomes and Sodalis infections in tsetse flies from Kafue National Park in Zambia. A total of 326 tsetse flies were sampled from the Chunga and Ngoma areas of the national park. After DNA extraction was conducted, the presence of S. glossinidius and trypanosome DNA was checked using PCR. The Chi-square test was carried out to determine whether there was an association between the presence of S. glossinidius and trypanosome infections. Out of the total tsetse flies collected, the prevalence of S. glossinidius and trypanosomes was 21.8% and 19.3%, respectively. The prevalence of S. glossinidius was 22.2% in Glossina morsitans and 19.6% in Glossina pallidipes. In relation to sampling sites, the prevalence of S. glossinidius was 26.0% in Chunga and 21.0% in Ngoma. DNA of trypanosomes was detected in 18.9% of G. morsitans and 21.4% of G. pallidipes. The prevalence of trypanosomes was 21.7% and 6.0% for Ngoma and Chunga, respectively. The prevalences of trypanosome species detected in this study were 6.4%, 4.6%, 4.0%, 3.7%, 3.1%, and 2.5% for T. vivax, T. simiae, T. congolense, T. godfreyi, T. simiae Tsavo, and T. b. brucei, respectively. Out of 63 trypanosome infected tsetse flies, 47.6% of the flies also carried S. glossinidius, and the remaining flies were devoid of S. glossinidius. A statistically significant association was found between S. glossinidius and trypanosomes (p < 0.001) infections in tsetse flies. Our findings indicated that presence of S. glossinidius increases the susceptibility of tsetse flies to trypanosome infections and S. glossinidius could be a potential candidate for symbiont-mediated vector control in these tsetse species.Tsetse flies are obligate hematophagous vectors of animal and human African trypanosomosis. They cyclically transmit pathogenic Glossina) are biological vectors of African trypanosomes which cause animal African trypanosomosis (AAT) and human African trypanosomosis (HAT) . Th. Th\u00aeQuic species . To solvas 60 \u00b0C .T. congolense subgroup-specific PCR were conducted to differentiate the subgroup Kilifi, Forest and Savannah using subgroup-specific primers using species-specific primers (T. b. rhodesiense), the serum resistance associated (SRA) gene PCR was performed using an amplification program with an initial denaturation step at 95 \u00b0C for 15 min followed by 35 cycles of 94 \u00b0C for 1 min, 68 \u00b0C for 1 min, 72 \u00b0C for 1 min and a final extension step of 72 \u00b0C for 10 min. When the ITS1 PCR generated a PCR product of between 500 bp and 800 bp band sizes, primers with PCR primers . To checS. glossinidius in all tsetse flies was determined using the primer pair GPO1F and GPO1R, which amplifies the 1200 bp product of the extrachromosomal plasmid, GPO1, of Sodalis [The presence of Sodalis . The ampAll PCR reactions included appropriate positive and negative controls. The PCR products were size-separated by electrophoresis in 1x TAE buffer on 1.5% agarose gel , stained with Ethidium bromide and visualized under UV light. Amplicon sizes were determined relative to a 100 bp DNA ladder.\u00ae and analysed using R software version 4.1.0 [S. glossinidius and trypanosomes were estimated using frequencies. The Chi-square test or Fisher\u2019s Exact test where appropriate were used to compare the prevalence of trypanosomes and S. glossinidius with sex, species and collection site of tsetse flies. They were also used to assess whether the presence of S. glossinidius was associated with trypanosome infections. All the statistics were considered significant at p \u2264 0.050.Data were entered into MS-Excel on 4.1.0 . The preG. morsitans and 56 were G. pallidipes, and 50 were from Chunga and 276 were from Ngoma sampling locations were male and 95 were female tsetse flies. Out of the total tsetse samples collected, 270 were ocations .G. morsitans and G. pallidipes, Chunga and Ngoma, and male and female tsetse flies are shown in 2 = 6.73, p = 0.009) and between G. morsitans and G. pallidipes tsetse flies were found with DNA of at least one trypanosome species, indicating an overall prevalence of 19.3% (95% CI: 15.41\u201323.96). The differences in prevalence of trypanosomes between = 0.009) . There wse flies .T. vivax, T. simiae, T. congolense, T. godfreyi, T. simiae Tsavo, and T. brucei brucei. Trypanosoma vivax was the most prevalent, and T. b. brucei was the least. Six trypanosome species were detected in all tsetse flies. These were T. congolense, eight had the T. congolense Kilifi subgroup, two had the T. congolense Forest subgroup, and one had T. congolense Savannah. Two tsetse flies had mixed T. congolense subgroups. Of these, one had a mixed infection of T. congolense Kilifi and T. congolense Forest. The other had T. congolense Forest mixed with T. congolense Savannah. Among 13 tsetse flies which were positive for T. b. rhodesiense was detected in either species of tsetse flies.No human infective T. simiae and T. godfreyi, three tsetse flies that had T. simiae and T. simiae Tsavo, two tsetse flies infected with T. congolense and T. simiae, one tsetse fly with T. congolense and T. vivax, one tsetse fly contained T. congolense mixed with T. b. brucei, one tsetse fly with T. b. brucei and T. vivax and one tsetse fly with T. simiae Tsavo and T. godfreyi. Triple infections were found in two tsetse flies which had T. simiae/T. godfreyi/T. simiae Tsavo and T. simiae/T. congolense/T. simiae Tsavo.Most tsetse flies were infected with a single trypanosome species , followed by tsetse flies infected by two trypanosome species and tsetse flies that had three trypanosome species . MultiplS. glossinidius from the 326 tsetse flies was estimated to be 21.8% (95% CI: 17.64\u201326.57). The prevalence was higher in female than in male tsetse flies , although this was not statistically significant . It was also slightly higher in G. morsitans than in G. pallidipes but not statistically significantly different . The prevalence between the two sampling sites was not significantly different , although it was slightly higher in Chunga (26.0%: 95% CI: 15.87\u201339.55) than in Ngoma .The overall prevalence of S. glossinidius in each tsetse species was examined based on sampling location and the sex of tsetse flies or between male and female flies (S. glossinidius between Chunga and Ngoma (p = 1.000) or between male and female (p = 0.142) G. pallidipes flies . There wes flies .S. glossinidius, while the remaining flies were devoid of S. glossinidius. The analysis performed on the overall dataset indicated that there was a significant association between tsetse flies harboring S. glossinidius and tsetse flies infected with trypanosomes . The association varied between sampling sites, with tsetse flies from Ngoma showing a statistically significant association , whereas tsetse flies from Chunga showed no statistically significant association (p = 0.162). In G. morsitans, twenty-five out of sixty tsetse flies with S. glossinidius were infected with trypanosomes, and there was a statistically significant association between the two pathogens. From the eleven S. glossinidius positive G. pallidipes tsetse flies, five had trypanosome co-infections, and the association was statistically significant (p = 0.045). A statistically significant association was also observed between S. glossinidius and trypanosome prevalence in male tsetse flies , but no such association was observed in female tsetse flies (p = 0.058) .T. simiae Tsavo, T. simiae, and T. vivax, the co-infection rates with S. glossinidius were 60.0%, 46.7%, and 47.6%, respectively. Among the tsetse flies infected by T. congolense, co-infection with S. glossinidius was 30.8%, and for T. b. brucei and T. godfreyi, the co-infection rate was 50.0% for both (S. glossinidius and T. vivax (p = 0.006), T. simiae (p = 0.025), T. simiae Tsavo (p = 0.009), and T. godfreyi (p = 0.027), but no such association was detected between S. glossinidius and T. congolense (p = 0.491) and T. b. brucei (p = 0.072) (Among the tsetse flies infected with for both . There w= 0.072) .S. glossinidius in tsetse flies collected from the Chunga and Ngoma areas of the Kafue National Park. The study also intended to determine whether an association between trypanosomes and S. glossinidius existed in these tsetse flies. Both Sodalis and trypanosomes were prevalent in tsetse flies obtained from the study area. The prevalence of trypanosomes found in this study was similar to the 17.4% prevalence reported from Ghana [The aim of this study was to determine the prevalence of trypanosome and om Ghana but loweom Ghana ,40, Luamom Ghana ,28,41, Nom Ghana , Shimba om Ghana , and Sanom Ghana . Howeverom Ghana , 3.4% from Ghana , 6.31% fom Ghana , 10.7% fom Ghana , and 11.om Ghana . These dT. vivax being the most prevalent. This is in agreement with another study that reported a high prevalence of T. vivax in tsetse flies and cattle in the same study area [T. simiae, T. congolense, T. godfreyi, T. simiae Tsavo, and T. b. brucei. The higher prevalence of T. vivax in tsetse flies compared with other trypanosome species may be due to the differences in development cycles as T. vivax completes its entire development only in proboscis, whereas T. congolense, T. simiae, T. godfreyi, and T. simiae Tsavo in complete it in the proboscis and midgut and T. b. brucei in the midgut and salivary gland, which can be affected by low pH, protease activity and lectins [In the current work, six trypanosome species were detected with udy area . The resudy area and otheudy area ,45. Othe lectins ,50. In this study, there were no significant differences in the levels of trypanosome infections between male and female tsetse flies. This result is similar to a finding from Chad and otheT. b. rhodesiense in vervet monkey, sable antelope, buffalo [T. b. rhodesiense was not detected in the current study, the presence of the most competent tsetse fly vectors of T. b. rhodesiense in KNP and the high prevalence of T. b. rhodesiense previously reported in wildlife [Despite a recent report of a HAT case in an adult male and the buffalo and in c buffalo from thewildlife and cattwildlife in the aS. glossinidius estimated from this study was lower than the 31.3% prevalence reported from southwest Nigeria [The overall prevalence of Nigeria and the Nigeria . However Nigeria and that Nigeria . S. glossinidius in relation to species of tsetse flies was not statistically significant. In G. morsitans, the prevalence of S. glossinidius was higher than the 17.5% reported in Luambe National Park, in eastern Zambia [S. glossinidius in G. pallidipes was higher than the 1.4%, 6.5%, 15.9%, and 16% recorded in Luambe National Park, Zambia [G. pallidipes collected from Tanzania [S. glossinidius genotypes and trypanosomes [The difference in the prevalence of n Zambia and the n Zambia . Howevern Zambia and the n Zambia . In this, Zambia , Maasai , Zambia , Shimba , Zambia , and tse, Zambia , respectTanzania . These danosomes .S. glossinidius between male and female tsetse flies was detected. This finding is in agreement with other studies by Dennis et al. [S. glossinidius between sexes of G. morsitans and G. pallidipes. In this study, no significant difference in the prevalence of s et al. and Maths et al. which reS. glossinidius and trypanosomes in this study were lower than the 37% rate reported from the \u201cFaro and D\u00e9o\u201d division of the Adamawa region of Cameroon [S. glossinidius is not absolutely necessary for tsetse flies to be infected by trypanosomes, but the presence of S. glossinidius would highly favor such infections. From the overall data analysed, the co-infection rate between Cameroon and the Cameroon , but higCameroon . This reS. glossinidius and the presence of trypanosomes in tsetse flies. This maybe an indication that presence of S. glossinidius favors trypanosome infections in tsetse flies. This is in agreement with other studies from Cameroon [S. glossinidius and trypanosome infections in different tsetse fly species. However, there was variation in the association of Sodalis and trypanosomes between tsetse fly species, sex and sampling locations. In the current study, significant associations were found between the presence of Cameroon , westernCameroon and KenyCameroon , where sSodalis and trypanosomes in G. morsitans and G. pallidipes . Significant associations were found between Sodalis and trypanosome infections in G. morsitans and G. pallidipes tsetse fly species. These findings are in line with other studies conducted in G. m. centralis [G. pallidipes [G. pallidipes and G. swynnertoni [G. p. palpalis [S. glossinidius and trypanosome infections were reported in the respective tsetse fly species. These findings support the hypothesis that presence of S. glossinidius increases the susceptibility to and establishment of trypanosome infections in G. morsitans and G. pallidipes tsetse flies. However, this is in contrast to the findings of a study of G. morsitans and G. pallidipes in tsetse flies from Luambe National Park, Zambia [Sodalis, this difference may be due to a difference in S. glossinidius genotype which may affect the association between S. glossinidius and trypanosome infections, as described by Geiger et al. [S. glossinidius and trypanosome infections in males, but no significant association was observed between the endosymbiont and trypanosome infections in females. These differences may be due to the small number of female tsetse flies collected for the endosymbiont and trypanosome infections. Separate analyses of the data for each sampling site indicate there are differences in the statistical association between the endosymbiont and trypanosome infections, where a statistically significant association was observed for the Ngoma sampling site, but not for the Chunga sampling site. This difference could be due to the low trypanosome infection rate and small number of tsetse flies captured at the Chunga sampling site. There were no large differences in the proportions of co-infected tsetse flies with entralis , G. pallllidipes , G. pallnnertoni and G. ppalpalis where si, Zambia where nor et al. . Based oS. glossinidius and each trypanosome species infection were also examined. The result of this analysis clearly indicates that significant associations were found between S. glossinidius and T. simiae, T. vivax, T. simiae Tsavo, and T. godfreyi. However, there were no significant associations between S. glossinidius and T. congolense and T. b. brucei. This difference is probably due to S. glossinidius affecting the establishment of trypanosomes depending on the trypanosome genotype [The associations between genotype . S. glossinidius and trypanosomes. One limitation of this study was that we could not discriminate between established infections and residual bloodmeal contamination as PCR detects trypanosome DNA in the fly bloodmeal, which can remain in the tsetse tissues after the death of the parasite. This could lead to higher prevalence estimates of trypanosomes than the true prevalence and further affect the association between S. glossinidius confirmed the presence of the endosymbiont in G. morsitans and G. pallidipes tsetse flies. The study confirmed the circulation of pathogenic trypanosome species in G. morsitans and G. pallidipes in the study area. The results also show that some tsetse flies were infected by both the endosymbiont and trypanosome, whereas others were infected by either the endosymbiont or trypanosome only, or had no infection at all. The association between S. glossinidius and trypanosome infections is complex and seems to vary according to tsetse fly sex and trypanosome species, with T. simiae, T. simiae Tsavo, T. vivax, and T. godfreyi being significantly associated with S. glossinidius. To increase understanding about the tripartite association and to use S. glossinidius as a potential target for genetic transformation to control vectors of trypanosomes, further research on genetic comparisons between S. glossinidius detected in tsetse flies co-infected with trypanosomes and S. glossinidius detected without trypanosome infections is required.Investigation of"} +{"text": "Various psychopathologies, including schizophrenia, bipolar disorder and major depression, are associated with abnormalities in social behavior and learning. One of the syndromes that may also take place in these disorders is catatonia. Catatonia is a psychomotor syndrome in which motor excitement, stereotypy, stuporous state, including the phenomenon of \u201cwaxy flexibility\u201d , can be observed. Rats with genetic catatonia (GC) and pendulum-like movements (PM) of the anterior half of the body have physiological and behavioral changes similar to those observed in schizophrenia and depression in humans and can be considered as incomplete experimental models of these pathologies. The social behavior of the GC and PM rats has not been previously studied, and the cognitive abilities of animals of these strains are also insufficiently studied. To determine whether the GC and PM rats have changes in social behavior and spatial learning, behavioral phenotyping was performed in the resident-intruder test, three-chamber test, Barnes maze test. Some deviations in social behavior, such as increased offensive aggression in PM rats in the resident-intruder test, increased or decreased social interactions depending on the environment in different tests in GC, were shown. In addition, principal component analysis revealed a negative association between catatonic freezing and the socialization index in the three-chamber test. Decreased locomotor activity of G\u0421 rats can adversely affect the performance of tasks on spatial memory. It has been shown that PM rats do not use a spatial strategy in the Barnes maze, which may indicate impairment of learning and spatial memory. In psychiatric classification, there is an acute issue of divisionand diagnosis of individual nosological units. A lot of evidencepointing to the generally continuous nature of psychopathologicalvariation versus discrete has been accumulated . In DSM-5 , there are many \u201cspectra\u201d and groupsof disorders , the symptoms of which overlap very strongly. Thecomorbidity observed between major depression and schizophrenia, bipolar disorder, attentiondeficit hyperactivity disorder, and autism implies that the same pathophysiological processes occur inthese diseases. In this regard, new concepts are being createdthat try to explain the pathogenesis of distinct psychiatricsymptoms and emphasize the exploration of endophenotypesbut not of complex diseases . Thisapproach solves the \u201cproblem of comorbidity\u201d by explicitlymodeling patterns of co-occurrence among signs and symptoms.One of the syndromes that can be used as a \u201cspecifier\u201d inDSM-5 for the characterization of several clinical phenotypesincluding schizophrenia spectrum disorders, affective, andneurodevelopmental disorders is catatonia . Catatonia is a psychomotor syndrome characterized byvarious signs: stupor, catalepsy ,stereotypy, mutism. This motor and behavioral alterationmay occur in many psychiatric conditions but predominantlyin schizophrenia, affective psychosis, autism . While many aspects of human psychopathologiescannot be simulated in animals, some symptoms of catatoniacan. Different animal models can help characterize the natureof specific psychopathology symptoms, and there are specialbehavioral parameters of potential relevance to signs andsymptoms of schizophrenia. Excessive catatonic reactions inanimals can also correspond to catatonia in humans and includepresence of bizarre motor activity, decrease in motor activity,or catatonic excitement (intense bursts of agitated stereotypy).For genetically based modeling of schizophrenia-relevantand catatonia-relevant symptoms, the GC (genetic catatonia)and the PM (pendulum-like movements) rat strains were offered. The strains were obtained by selectionfor intensification of such catatonic reactions as freezingor catalepsy (GC strain) and stereotyped pendulum movements(PM strain). The GC rats demonstrate occasional freezingor, instead, hyperkinetic behavioral reactions that resemblethe manifestations of the catatonic syndrome . These reactions can be spontaneous, as well as inresponse to a weak stressful stimulus, such as in a special testfor catatonic freezing . In addition, rats of this strainare characterized by increased stress reactivity , increased shock-induced aggression , impaired filtration of sensorimotor information(manifested by a deficiency of PPI) .PM rats are characterized by rhythmic side-to-side rockingof the head and forebody in the absence of locomotion . More than that, rats selected for an increasedamplitude of pendulum-like movements after the 40th generationstarted generating seizures to audiogenic stimulation.Despite some parameters supporting face validity of thismodel, phenotype of these strains is not yet well explored. Forexample, aspects of behavior and cognitive activity such associal interactions and learning are also of interest. A varietyof neuropsychiatric disorders are characterized by disruptionsin social behavior and social recognition, including depression,autism spectrum disorders, bipolar disorders, obsessive-compulsivedisorders, and schizophrenia. In animals, altered socialinteraction responses in a variety of situations are consideredas analogs related to negative \u2013 social withdrawal \u2013 symptomsof schizophrenia , hyperactivity andaggressive behavior directly related to positive symptoms ofschizophrenia .To determine whether selection for predisposition to thecatatonic freezing and the amplitude of pendulum-like movementsinfluenced social interactions and learning in the GCand PM rat strains, behavioral phenotyping of rats in theresident intruder test, three-chamber test, Barnes maze testwas carried out.The study was carried out on male rats of the GC (geneticcatatonia), PM (pendulum-like movements), Wistar andWAG (Wistar Albino Glaxo) strains. Since the PM rat strainis outbred, rats of the outbred Wistar strain were used as acontrol, while for the inbred GC, the inbred WAG were used.Experiment 1 included the catatonic freezing test ; the three-chamberparadigm test and the resident-intruder test (5 days afterthe three-chamber test). In the Experiment 2, another 60 rats were testedin the Barnes mazeRats were kept under standard vivarium conditions witha free access to food and water. All experimental procedurescomplied with the rules and regulations formulated in theEU Council Directive 1986 (86/609/EEC) and the Declarationof Helsinki on the protection of vertebrate animals usedin experimental research and approved by the ICG SB RASBioethics Committee .Experiment 1. Social behavior and catatoniaThe catatonic freezing test is a selection criterion for theGC rats and was carried out according to the protocol . To determine the presence or absence of freezing reactions and their duration, the rat was uplifted in the cornerof the cage by the forelegs using a test stick. The freezing timewas estimated as a time during which the animal retained theinduced posture or freezing position on 4 paws after the stickwas removed. Rats were tested two times on different days.The three-chamber paradigm test. The three-chambersocial interaction assay was performed to assess socialdeficits according to the protocol . Testing was carried out in a test arena manufacturedby OpenScience, Russia, model TS1701-R. The apparatusfor the test is comprised of a rectangular, three-chamber box.Each chamber is 40 \u00d7 85 cm and the dividing walls are madefrom clear Plexiglas, with an open middle section, whichallows free access to each chamber. For habituation, the testrat was placed into a Plexiglas\u2019s arena containing two emptycylindrical containers in two side chambers for 10 minutes.Session I. Wistar males of the same weight without anyprior contact (not littermates) with the subject were used ascontrol animals (Stranger 1 and Stranger 2). One of the controlrats (Stranger 1) was placed in one of the containers locatedin one of the side chambers. The placement of Stranger 1 onthe left or right side of the chamber was systematically alteredbetween trials. After removing the walls between the compartments,the following parameters were monitored and recorded:duration of direct contacts of the subject rat with Stranger 1;duration of contacts with empty enclosure. The duration of sessionI was 10 minutes. Then the Session II began. The secondcontrol rat was placed in the empty cylinder in the oppositeside chamber. Duration of direct contacts of the subject ratwith Stranger 1 and Stranger 2 were monitored and recordedwithin 10 minutes. The socialization index was calculatedby the formula (T1 \u2013 T0)/(T1 + T0)\u00d7100 %, where T1 is the timeof contact with the containment cup housing Stranger 1 rat;T0 \u2013 time of contact with the empty enclosure. The social noveltyindex is calculated by the formula (T2 \u2013 T1)/(T2 + T1)\u00d7100 %, where T1 is the time of contact with familiar rat (Stranger 1),T2 is the time of contact with the container housing Stranger 2rat. The freezing time in this test was also recorded at eachsession The resident-intruder test. To measure offensive aggression,the resident-intruder test was performed according tothe standard protocol . To assess thedefensive behavior of resident males of the studied strain, theywere placed in cages for 7 days before the test. To preserveolfactory signals, the cage was not cleaned before the test. Theintruder was placed in theresident\u2019s cage through the partition, then the partition wasremoved. Testing was carried out for 10 minutes. Durationsof the behavioral parameters were registered: (1) total offense:sum of lateral threat, upright, clinch and keep down; (2) socialexploration: sum of social explore, ano-genital sniffing andmove towards; (3) non-social activity: non-social explore,rearing, grooming; (4) inactivity, including rest and freezing(freezing in the RI). Also the numbers of mounts and attacklatencies were analyzed.The analysis of the main factors determining the variabilityof behavior characteristics in Experiment 1 was investigatedby the Principal Component Analysis.Experiment 2. Spatial learningThe Barnes maze was used to test the acquisition of spatialmemory. Testing was carried out in a setup manufactured byRPC OpenScience, Russia, model TS1101-R . Testingin the Barnes maze included 3-minute training sessions oncea day for 5 days . Probe trial wasadministered 24 hours after the acquisition session (Day 7).The following parameters were to be calculated: (1) primarylatency, (2) primary errors, (3) distance moved (in cm), and(4) velocity (cm/s) .Video tracking and registration of behavioral parameterswere carried out using the program EthoVision XT 15 . In addition, on 4, 5 and 7 day trialwas classified into 1 of 3 categories of search strategy reflecting the use of either a direct spatial strategy, a serial strategy or a mixed strategy .The data were subsequently analyzed in terms of percentageof trials with a direct spatial strategyThe obtained data were processed using STATISTICA 10.0.In the paper, data are presented as mean \u00b1 SEM. Behavioralscores from Experiment 1 were analyzed by Student t-tests.When comparing a rate, Fisher\u2019s exact test was used. Theanalysis of the main factors that determine the variability ofbehavior characteristics in Experiment 1 was investigatedby the principal component analysis. In Experiment 2, comparisonsof components were made using the Mann\u2013WhitneyU test. Data analysis from the training sessions of Barnes mazewas carried out using repeated measures ANOVA, followedby Fisher LSD post hoc analyses to analyze group differences.Statistical evaluation of the probe trial data was performedusing one-way ANOVA, Fisher LSD post hoc analysesExperiment 1. Social behavior and catatoniaThe catatonic freezing test revealed a mean duration of freezingin the GC and PM rats is by far longer than in the controlrats . In addition,a rate of rats in populations that freeze for longerthan 10 seconds was estimated. In the GC (95.5 %) andPM (77.3 %) strains, the rate is significantly higher than inthe control strains .A study of behavior in the three-chamber paradigm testshowed a decrease in the sociability index in the GC rats(18.6 \u00b1 10.2) compared to WAG (56.0 \u00b1 10.1) (p < 0.05). Thesociability index in the PM rats (35.7 \u00b1 15.4 vs 44.6 \u00b1 14.6),as well as the social novelty index in both groups did not differ from the controlIn the resident-intruder test the parameters of resident\u2019sbehavior in the home cage when adding an intruder wereregistered and combined in categories (see Methods). Theanalysis revealed an increased level of social exploration ofPM versus Wistar, as well as GC compared to WAG (p < 0.05). Moreover, unlike the GC, PM rats exhibited moreaggressive behavior both in total duration (p < 0.05) andshort attack latencies (90.3 \u00b1 16.9) compared to Wistar. In addition, the GC and PM strainsshowed significantly increased sexual behavior (p < 0.01),which was estimated in the number of mounts .Non-social activity of the GC and PM rats was significantlylower compared to control (p < 0.05 and p < 0.001), while thetime of inactivity was higher (p <0.05). Thus, the behaviorof the GC and PM rats in the home cage when the intruder isplaced shifts towards an increase in social interactions with adecrease in exploratory activity.The principal component analysis of Experiment 1 parametersproduced three factors with eigenvalues greater than 1.These three factors explain 57 % of the variance in the correlationmatrix. The factor patterns are presented in the Table.Component 1 (24.1 % of variance) was explained by stuporin the catatonic freezing test (\u20130.69) and in the three-chamberparadigm test andsociability index value (0.59).Component 2 (18.7 % of variance) was mainly loaded bynumber of mounts (0.74) and total duration of non-aggressivesocial behavior (0.66) in the resident-intruder test.Component 3 (14.2 % of variance) was loaded by the totalduration of aggressive behavior (0.71) and duration of immobility(0.57) in the resident-intruder test.Mann\u2013Whitney U test procedures showed a strain effect forComponent 1 in PM and Wistar rats (p < 0.001) .For WAG and GC, a significant difference was shown in Component1 (p <0.001) and Component 2 (p < 0.01) .Experiment 2. Barnes maze taskThe data analysis revealed that latency time for the GC groupwas significantly increased in the probe trial when comparedto the WAG group . Nodifference was found between PM and Wistar. The averagevelocity of movement across the maze field did not differfor Wistar and PM. Comparison of GC and WAG rats speedrevealed a significant effect of the test day and the interaction of factors of the genotype andthe test day on the speed wasfound. The average velocity of movement across the maze fieldwas significantly lower for GC in day 3 , in day 4 (p < 0.05), in day 5 (p < 0.05) and in the probe trial . Total distance moved did not differ between groups.The use of spatial strategy increased with the training duringthe acquisition phase, except for the PM group: in the 7th day of trials, the incidence of spatial strategy in the PM rats was0 % (0/15) compared to 46.7 % (7/15) in the Wistar rats .There was no significant effect of genetic group on themean number of errors per trial made during the probe trial.Experiment 1. Social behavior and catatoniaDecreased sociability in the three-chamber test shown byGC rats in this work is consistent with literature data aboutsocial abnormalities in different animal models of psychopathologies.Most of the animal models of schizophrenia havedecreased or normal social interaction . In particular, in the model of negative symptomsof schizophrenia in animals induced by NMDA-receptor antagonists,social interaction deficits have been shown . DISC-1 mutations known to cause schizophrenialikeabnormalities in rodents can impairs cognitive and socialbehaviors in some transgenic mice , but not in rats . Research of knockouts of the Neuregulin-1 (NRG1)gene which has been identified as a candidate susceptibilitygene for schizophrenia, revealed a selective impairment inresponse to social novelty in NRG1 mutants, but not in sociability. Developmental models ofschizophrenia, such as using neonatal lesions of the rat ventralhippocampus or prenatal administration of methylazomethanolinto pregnant rats, result in deficits in social behavior, as wellas impaired memory, and increased anxiety . Another selective breedingmodel of psychopathology that exhibits increased freezingto context (but unlike rats of the GC strain only onto acuteprior stress) is the Wistar Kyoto (WKY) rats . WKY is a depression model characterized by elevatedanxiety- and depression-like behavior. In the social interactionassessment, the WKY rats avoided contact with another rats.However, in the resident-intruder test, the total time thatthe GC and PM rats spent on direct contact with a social object(intruder) was significantly higher than that of control.This discrepancy in social activity in the two tests may beexplained by different environmental conditions that affectemotional state and motivation. Stress level of the threechambertest is mostly caused by placing the experimentalanimal into a novel environment by the experimenter. Earlier it was shown that the GC rats react more strongly even to thehandling required to place the animal in the experimentalsetup: corticosterone concentrations were increased duringhandling, but reduced at rest . Suchan increased stress reactivity in the GC rats may explain thedecrease in sociability index in the three-chamber test due tothe passive-defensive reaction in response to handling stressin the three-chamber test, but not in the resident-intruder test,which does not require handling. Previously, it was shown thatpassive-defensive reflex expressed in the form of catatonicstupor is of dominant character and significantly prevails overcognitive and alimentary reflexes . The resultsof this work suggest that the predisposition to catatonic stuporalso negatively affects social motivation during testing in thethree-chamber paradigm.The data on the increase in social contacts of both GC ratsand PM rats in the resident-intruder test shown in this workare of interest. It is known that an increase in social interactionin rodents can be achieved in certain ways, such as medialprefrontal cortex lesions or low dosesof ethanol . At the neurochemicallevel, a wide variety of systems have been examined for theirrole in the normal expression of social behavior . Oxytocin, vasopressin, endogenous opioids andcatecholamines appear to participate in a wide variety ofaffiliative behaviors . Acute administrationof opiate drugs, low dose morphine and naltrexoneproduced a more robust attenuation of social investigation thannon-social exploratory activity in rats. Amphetamine increasedboth forms of investigation and haloperidol had the oppositeeffect . More than that, there is evidenceof the involvement of the glutamate system in the formationof social deviations. D-Cycloserine, a partial agonist at theglycine recognition site of the glutamatergic NMDA receptor,can increase social investigation and sexual behavior anddecrease aggressiveness in mice . There areresults supporting a role of glutamate receptors subunits inthe modulation of social behavior , however the study of the glutamatereceptors genes mRNA in the hippocampus and frontal cortexof the GC rats did not reveal any changes .The increased mounting in the GC and PM rats shownin this paper may be indicative of aggressiveness betweenrats of the same sex. It has previously been shown that the GC rats demonstrate a high level of shock-induced aggression, but not aggression towards malerats or interspecies aggression towards mice . In addition, both PM and GC rats have an increasedaggressive response towards humans .Considering the fact that PM rats, in addition to catatonicsymptoms, have a predisposition to audiogenic seizures, theconnection between epilepsy and psychopathology in humansshould be mentioned. Many symptoms of neurologic or psychiatricillnesses \u2013 such as cognitive impairment, depression,anxiety, attention deficits \u2013 occur more frequently in peoplewith epilepsy than in the general population . The rat lines selectively bred for differences inamygdala excitability, manifested by \u201cfast\u201d or \u201cslow\u201d kindlingepileptogenesis, display several comorbid features relatedto anxiety and learning. Seizure-prone genetic backgroundprovides poorer original learning and easier disruption ofnew learning, as well as increased anxiety and impulsivity. Rats in the chronic phase of thelithium-pilocarpine model of epilepsy showed disturbedcommunicative behavior, with impaired social behavioralpatterns, increased motor activity and impaired memoryfunction . Aggression is one of severalpsychiatric disorders that is observed, among others, inepileptic patients . This association hasbeen reliably replicated in several animal models includingthose using pilocarpine and domoicacid , in which aggression developseither in parallel to spontaneous seizures or precedes thedevelopment of recurrent seizures. The increased offensivebehavior of the PM rats in the resident-intruder test shown inthis work may confirm the likely relationship between seizurepredisposition and aggressiveness.Experiment 2. The Barnes maze taskRodent basal cognitive abilities include, along with elementarylogic tasks solutions and generalization capacity of a low level,spatial behavior and memory. This type of cognitive abilityrequires the formation of mental representations of spatialenvironmental characteristics . Totest the acquisition of spatial memory in PM and GC, theBarnes maze was used. The increased time required to searchfor the target hole in the GC rats may indicate impaired spatiallearning. However, a decreased locomotor activity has earlierbeen shown in rats of this line , and to assesswhether potential disturbances are in fact memory impairmentsit is necessary to take into account such parametersas primary errors and search strategy. No differences wereshown for these parameters in GC compared to WAG. Thereduced GC rats velocity of movement across the maze fieldfor 3\u20137 days confirms the effect of motor activity on latencyto first target visits. The GC rats appear to have no learningimpairment in this test. The fact that the velocity of movementof the GC rats in the field does not differ in the first two daysof testing, but is less than in the control on the following days,may indicate a slower adaptation to new conditions.Estimation of the search strategy showed differences inPM in comparison with Wistar. After a few days of training,non-cognitively impaired animals frequently use the spatial strategy to resolve the BM task. The fact that after a few daysof learning trials the PM rats still use mixed andserial strategies instead of spatial to resolve the maze meansthat they are cognitively impaired and do not employ spatialclues to reach the target hole . It has previouslybeen shown that the PM rats exhibit longer latency andlower rate of successful trials in the Morris water test, at thesame time, the GC rats did not differ from the control in theseparameters . The Morris water mazeis more stressful for animals than the Barnes maze, becausethere is water immersion . Water-mazetraining induced greater increases in plasma corticosteronewhich may affect the performance of animals . In addition, the GC rats are inclined to passive driftand longer floating episodes in the Morris water test . Low movement speed in Barnes\u2019s maze, hightime of inactivity and low exploratory activity in the residentintrudertest in the GC rats are caused by catatonic freezing.The data shown in this work confirm the manifestation ofcatatonic inhibition by the GC rats in different stressful situations.Selection for the duration of catatonic freezing and the amplitudeof pendulum-like movements influenced social interactionsand learning in the GC and PM rat strains. In particular,the GC rats have increased or decreased social interactionsdepending on the environment, and a negative relationshipbetween catatonic freezing and sociality were shown in thiswork. The PM rats show increased social activity and offensiveaggression in the resident-intruder test. 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In the face of climate and environmental changes, the study of hybrids of triatomines has evolutionary and epidemiological implications. Therefore, we performed morphological, cytological and molecular studies and characterized the feeding and defecation pattern of hybrids from crosses between T. sordida and T. rosai. The morphological characterization of the female genitalia of the hybrids showed that characteristics of both parental species segregated in the hybrids. Cytogenetic analyzes of hybrids showed regular metaphases. According to molecular studies, the mitochondrial marker Cytochrome B (CytB) related the hybrids with T. sordida and the nuclear marker Internal Transcribed Spacer 1 (ITS-1) related the hybrids with T. rosai. Both parents and hybrids defecated during the blood meal. Thus, the hybrids resulting from the cross between T. sordida and T. rosai presented segregation of phenotypic characters of both parental species, 100% homeology between homeologous chromosomes, phylogenetic relationship with T sordida and with T. rosai , and, finally, feeding and defecation patterns similar to the parents.Under laboratory conditions, Trypanosoma cruzi obtained from T. sordida (n = 4), T. rosai (n = 4) and their hybrids (n = 4) as well as from T. infestans (placed as outgroup) (Sequences of two molecular markers [Cytochrome B (utgroup) were subCytB and GTR for ITS-1.The best nucleotide substitution model for each marker was determined using the jModelTest 2 program , being HThe phylogenetic reconstruction by Bayesian approach was performed in MrBayes 3.2 for eachT. rosai, T. sordida, and experimental hybrids were evaluated based on Diotaiuti et al. [p \u2264 0.05. Analyzes were conducted in Jasp 0.16.2 [The feeding and defecation dynamics of i et al. with modp 0.16.2 . All aniT. rosai \u2640 and T. sordida \u2642 showed that in dorsal view (T. rosai pattern (tenth segment form) and T. sordida pattern was observed; in posterior view and intermediate pattern (shape and length of the tenth segment) was notified, and in ventral view (T. sordida pattern (line that divides the seventh and eighth gonocoxites segment and gonapophysis and shape of the eighth gonocoxites) was segregated.Morphological ,38,39,40sal view A,D,G, T.ior view B,E,H, T.ral view C,F,I, onT. sordida \u2640 and T. rosai \u2642 showed that in dorsal view and T. rosai pattern (form of the eighth segment) were observed; in posterior view was notified, and in ventral view (T. rosai pattern (line dividing the seventh segment and the eighth gonocoxites and gonapophysis and form of the eighth gonocoxites) was segregated.The morphological characterization of the female genitalia of the hybrids resulting from the cross between sal view A,D,G, T.ior view B,E,F, onral view C,F,I, onT. sordida and T. rosai, as well as divergent patterns were characterized in the genus Triatoma Laporte, 1832: hybrids resulting from the crosses between T. b. brasiliensis Neiva, 1911 \u2640 x T. lenti Sherlock & Serafim, 1967 \u2642, T. juazeirensis Costa & Felix (2007) \u2640 x T. lenti \u2642, and T. melanica Neiva & Lent, 1941 \u2640 x T. lenti \u2642 showed segregation of characteristics of both parental species [T. lenti x T. sherlocki Papa et al. (2002) and between T. juazeirensis x T. sherlocki showed intermediate characteristics [T. lenti \u2640 x T. juazeirensis \u2642, T. b. macromelasoma Galv\u00e3o, 1956 \u2640 x T. lenti \u2642, T. lenti \u2640 x T. melanica \u2642, and T. infestans and T. rubrovaria showed a specific pattern of T. lenti, T. lenti, T. melanica, and T. rubrovaria, respectively [The study of the segregation of phenotypic characteristics in Triatominae has been carried out for over 50 years . Both se species , hybridseristics ,42, hybrectively ,43.T. brasiliensis subcomplex and, based on the observation of different patterns , they highlighted the importance of integrative taxonomy for the correct identification of Chagas disease vectors grouped in the subcomplex if natural hybridization events occur. In addition, in the studies presented by Almeida et al. [T. sherlocki with the macropterous T. juazeirensis, the hybrids presented intermediate patterns, which provided greater fitness than the parents in the home invasion process .Morphological studies on hybrids have taxonomic, evolutionary and epidemiological importance ,43,44,45a et al. who crosT. sordida and T. rosai hybrids (both gender combinations) showed regular metaphases, with 100% pairing between the homologous chromosomes gene [CytB . Despite this, we could observe a significant difference in feeding (p = 0.005) and defecation (0.009) times between males and females (grouping data for each species and hybrids), the shortest times being observed for females. These results are important from an epidemiological point of view, as a good vector of Chagas disease, in general, has a shorter period of time between the beginning of blood ingestion and first defecation, depositing T. cruzi while still feeding [The feeding and defecation pattern of valuated . Both pavaluated , however feeding .T. mazzottii Usinger, 1941, T. pallidipennis, and T. phyllosomus Burmeister, 1835 and their laboratory hybrids, as well as T. pallidipennis, T. longipennis, T. picturata, and their laboratory hybrids were evaluated [T. cruzi than their parental species. In the same way, L\u00f3pez et al. [T. infestans and T. platensis Neiva, 1913 and, based on the blood ingestion velocity, the amount of blood ingested, and the short time required for the production of the first defecation, the hybrid can be considered as a competent T. cruzi vector.The time interval before beginning of feeding, for feeding, and until defecation for valuated ,18,19,20z et al. analyzedT. sordida and T. rosai presented segregation of phenotypic characters of both parental species, 100% homeology between metaphase chromosomes, phylogenetic relationship with T sordida (with the CytB gene) and with T. rosai (with the ITS-1 molecular marker) and, finally, feeding and defecation patterns similar to the parents, highlighting the possible vector competence of these insects for Chagas disease .Based on the above, the hybrids resulting from the cross between"} +{"text": "In the original publication , the refRadiat. Res.2019, 192, 538\u2013561.6. Paulbeck, C.; Griffin, K.; Lee, C.; Cullings, H.; Egbert, S.D.; Funamoto, S.; Sato, T.; Endo, A.; Hertel, N.; Bolch, W.E. Dosimetric Impact of a New Computational Voxel Phantom Series for the Japanese Atomic Bomb Survivors: Pregnant Females. With this correction, the order of references has not been changed. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "ES&T paper (https://doi.org/10.1021/acs.est.1c04780) has an extensive data set associated with it. Unfortunately, dueto a production error, the citation to reference 55 omitted the DOIof the database. The corrected reference is as follows:Our recently published Data set for hydroxylated polychlorinated biphenylsare emerging legacy pollutants in contaminated sediments;University of Iowa, 2021. https://doi.org/10.25820/data.006146Saktrakulkla,P.; Li, X.; Martinez, A.; Lehmler, H.-J.; Hornbuckle,K. C. In addition, the original article on the ACS publicationswebsitehas been updated to show the correct reference 55."} +{"text": "Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease with a prevalence of 2 to 29 per 100,000 of the world\u2019s population. Aging is a significant risk factor for IPF, and the mechanisms of aging are involved in the pathogenesis of IPF. The pathogenesis of IPF consists of TGF-\u03b2 activation, epithelial-mesenchymal transition, and SIRT7 expression decrease. Genetic studies have shown a role of mutations and polymorphisms in mucin genes (MUC5B), in the genes responsible for the integrity of telomeres , in surfactant-related genes , immune system genes , and haplotypes of HLA genes in IPF pathogenesis. The investigation of the influence of reversible epigenetic factors on the development of the disease, which can be corrected by targeted therapy, shows promise. Among them, an association of a number of specific microRNAs and long noncoding RNAs was revealed with IPF. Therefore, dysregulation of transposons, which serve as key sources of noncoding RNA and affect mechanisms of aging, may serve as a driver for IPF development. This is due to the fact that pathological activation of transposons leads to violation of the regulation of genes, in the epigenetic control of which microRNA originating from these transposons are involved (due to the complementarity of nucleotide sequences). Analysis of the MDTE database (miRNAs derived from Transposable Elements) allowed the detection of 12 different miRNAs derived in evolutionfrom transposons and associated with IPF . We described the relationship of transposons with TGF-\u03b2, sirtuins andtelomeres, dysfunction of which is involved in the pathogenesis of IPF. New data on IPF epigenetic mechanisms canbecome the basis for improving results of targeted therapy of the disease using noncoding RNAs. Idiopathic pulmonary fibrosis (IPF) is a progressive severeinterstitial lung disease. The annual incidence of IPF is up to17.4 per 100,000 people in the world .The prevalence of IPF in different countries ranges from 2 to29 per 100,000 people ; in theUSA \u2013 14\u201342,7 per 100,000 people). IPF is associated withaging. Therefore, for people over 75 years of age, the prevalenceof the disease is 227.2 per 100,000, while for peopleaged 18 to 34 years, the prevalence of IPF is 4 per 100,000.The average age of patients with IPF is 66 years . Survival for IPF is about 3 years after diagnosis, andavailable drugs only slow the decline in lung function withlittle to no effect on mortality .IPF pathogenesis involves environmental influences andmicroorganisms . Viral , bacterial and fungal infections play a potentialrole in the development of IPF . Smokingand metal dust inhalation are also associated with the riskof IPF . The developmentof IPF is affected by occupational hazards, suchas contact with silicon, beryllium, coal dust, asbestos, andradiation. In addition, IPF is associated with anti-inflammatorydrugs , chemotherapy drugs, heart drugs , and antibiotics . In 2019, a meta-analysis including3206 patients and 9368 healthy individuals showed the roleof gastroesophageal reflux disease in the development of IPF.According to the generally accepted hypothesis, IPF developsas a result of immune reactions to restore the structureof lung tissue in case of repeated damage to the alveolarepithelium or endothelium. In this mechanism, the inflammatorymediator profibrotic cytokine \u2013 transforming growthfactor \u03b2 (TGF-\u03b2) activates angiogenesis and the production ofextracellular matrix components (collagen and fibronectin).Failure to inactivate the fibrotic trigger leads to an exacerbationof the inflammatory response with excessive depositionof matrix components and lung scarring . Molecular mediators of IPF include cell surface proteins,intracellular proteins, and soluble molecules (cytokines).The development of IPF is associated with sirtuins, a familyof histone deacetylases that require NAD+ for their catalyticactivity. The expression of sirtuins in fibroblasts of patientswith IPF is significantly reduced. Similarly, a decrease inthe concentration of SIRT7 in lung tissues was found in experimentalmouse models with IPF induced by bleomycin. Inhibition of SIRT7 in fibroblast cultures by siRNA causedan increase in collagen synthesis. Overexpression of SIRT7 inlung fibroblasts leads to lower levels of COL1A1, COL1A2,COL3A1, exerting an antifibrotic effect .In the pathogenesis of IPF, an important role is played by theepithelial-mesenchymal transition, during which the expressionof adhesion molecules (E-cadherin) is suppressed, andthe cytokeratin cytoskeleton is transformed into a vimentinone. Accordingly, epithelial cells acquire a mesenchymalmorphology . However, there is still nocomplete theory that would fully explain the mechanism ofIPF development. The most accurate data on the pathogenesisof IPF can be obtained using molecular genetic studies, whichare promising for identifying the individual risk of the diseaseand developing its effective targeted therapy .Familial IPF involving two or more family members averages10 to 15 % of all IPF cases . Thereare sporadic, familial and syndromal forms of IPF . Sporadic cases of thedisease are multifactorial diseases, that is, their developmentis influenced by environmental factors. These forms comprisethe majority of IPF cases and are associated with polymorphicvariants of various genes (Table 1). Risk factors for sporadicIPFs are male gender, smoking, inhalation of metal and wooddust, or use of certain medications such as methotrexate andbleomycin . Familial IPFs are similarto sporadic, but are characterized by an earlier manifestation.They are caused by mutations in certain genes (see Table 1).Familial IPFs were first described in 1958 by McKusickand Fisher as an autosomal dominant disorder with variablepenetrance . Up to 18 % of allfamilial IPFs are caused by mutations in the genes of telomerasecomponents: TERT \u0438TERC (r.37a>g) . Exome sequencingalso made it possible to identify rarer forms of familial IPFcaused by mutations in the helicase gene that regulatestelomere elongation and in the deadenylationnuclease gene .Cases of familial IPF caused by a mutation in exon 5(+128T>A) in the SFTPC surfactant protein gene are alsodescribed .Syndromal IPF develops in autosomal recessive Hermansky\u2013Pudlak syndrome, which is caused by an AP3B1 gene mutation (encodes an intracellular traffic protein). In this case,the specific mutations in the AP3B1 gene are the following:c.1525C>T (p.R509X), c.1739T>G (p.L580R), IVS10+5G>A,IVS11\u20131G>C .The promoter region of the mucin gene (MUC5B) containsa highly conserved polymorphic variant rs35705950 for primates,which is associated with sporadic and familial formsof IPF . SFTPC gene polymorphisms are associated withsporadic IPF . In this form of IPF,shortening of the telomeres of circulating lymphocytes wasrevealed, which indicates the role of changes in the TERTand TERC genes . According to epidemiologicaldata, familial forms with autosomal dominantinheritance range from 0.5\u20132 % (in the USA) to 3.3\u20133.7 % (in Finland) of allcases of IPF.The most reliable data on the genes involved in the pathogenesisof IPF can be obtained from large-scale studies usinggenome-wide association studies (GWAS). A meta-analysis offive studies of IPF patients compared with healthy controls revealed the haploblock VNTR*2 ofthe IL1RN gene (encodes an interleukin-1 receptor antagonist),associated with susceptibility to the development of sporadicIPF . In a study of 544 patientswith IPF, associations with various alleles of the TOLLIP gene, the SPPL2C gene allele(rs17690703), and the MUC5B gene allele (rs35705950)were found. The TOLLIP gene encodes a Toll-interactingprotein involved in the innate immune system; the SPPL2Cgene encodes a lysosomal membrane protein with a conservedtransmembrane domain . The role of theMUC5B allelic variant (rs35705950) in the predisposition toIPF was confirmed in a meta-analysis of 2859 patients withIPF (control group consisted of 6901 people) . The Tollip protein plays an important role inmodulating the transport and degradation of TGF-\u03b2 . These results are consistent with the role of TGF-\u03b2in the pathogenesis of IPF .A GWAS conducted in 2016 on 1616 patients (control \u20134683 people) showed the association of two haplotypes ofthe genes of the major histocompatibility complex (HLA):DRB1*15:01 and DQB1*06:02 with the development ofIPF. It allowed researchers to suggest the role of autoimmuneprocesses in the development of IPF .A GWAS conducted in 2020 on DNA samples from 2668 patientsshowed an association of sporadic IPF with alleles ofgenes MUC5B (rs35705950), TERC (rs12696304), TERT(rs7725218), DSP , ATP11A , IVD , AKAP13 , FAM13A , DPP9 .Thus, according to most genetic studies, IPF is associatedwith allelic variants of the genes responsible for the productionof mucin, the functioning of telomeres and the immune system,which indicates a complex pathogenesis of the disease. In addition,IPF is associated with aging. At the molecular level,IPF development involves processes characteristic of aging,including telomere depletion, genomic instability, mitochondrialdysfunction, cellular senescence, and loss of proteostasis. One of the causes of aging is thedysfunction of the immune system and telomeres caused byimpaired transposon expression . This is dueto the fact that in evolution, transposons became sources ofthe nucleotide sequence of both telomeres and telomerase encoding genes .In Drosophila, the role of telomerase is performed directly byretrotransposons: TAHRE (Telomere Associated and HeT-ARelated), TART (Telomere Associated Retrotransposon) \u0438HeT-A . In humans,the ability of LINE1 retrotransposons to participate in alternativetelomere elongation was revealed . Transposons likely play a role in the IPF pathogenesis,since familial IPF is most often caused by mutations in thegenes maintaining telomeres (the TERC and TERT genes), while sporadicforms of IPF are associated with polymorphic variants of thesegenes .Transposons serve as the basis for the epigenetic regulationof ontogenesis . Transposonsare specific genome structures capable of moving to a newlocus and occupy 45 % of human DNA. They are classifiedinto DNA transposons (movement by the \u201ccut and paste\u201dmechanism) and retrotransposons (movement with reversetranscription of mRNA and insertion of cDNA) .Epigenetic factors include DNA methylation, histone modificationsand chromatin remodeling, as well as RNA interferencevia non-coding RNAs. Transposons are the most importantsources of miRNA genes during evolution, in connectionwith which the MDTE (miRNAs derived from TransposableElements) database was created in 2016 .Data from this database are taken from the results of the workof various authors .Investigation of miRNAs can provide information about IPFpathogenesis, as well as become the basis for the developmentof effective disease therapy. Lung fibroblasts play an importantrole in the initiation and progression of IPF. Investigation ofmicroRNA expression in these cells revealed a decrease inmiR-101 levels in human patients with IPF and in experimentalmodels (bleomycin-induced pulmonary fibrosis) . In the development of IPF, dysregulation ofvarious miRNAs that affect the TGF-\u03b2 signaling pathways,which induce cell differentiation, migration, invasion, andhyperplastic changes, was revealed. These microRNAs includemiR-21, miR-424 (profibrotic); miR-9-5p, miR-18a-5p,miR-26a, miR-27b, miR-101, miR-153, miR-326, miR-489,miR-1343 (antifibrotic) .A pronounced imbalance in the expression of microRNAfamilies miR-29, miR-21-5p, miR-92a-3p, miR-26a-5p, let-7d-5p in IPF was found, and therefore these molecules areconsidered as potential therapeutic targets for treatment of thedisease . In human lung epithelium withIPF and mice with bleomycin-induced lung fibrosis, a decreasein the level of miR-323a was found, which attenuates TGF-\u03b1and TGF-\u03b2 signaling . MiR-21 also influencesthese signaling pathways. The expression of miR-21is increased in lung tissues of IPF patients and experimentalmice. MiR-21 is produced by fibroblasts and regulates Smad7expression by influencing TGF-\u03b21, promoting extracellularmatrix hyperproduction . Low expressionof miR-184 in IPF patients correlates with high levels ofp63 oncosuppressive protein, knockdown of which reducesTGF-\u03b21-induced lung fibrosis. It was found that miR-184binds complementarily to the 3\u2032-UTR of the mRNA of theTP63 gene, suppressing its expression .Among the microRNAs listed above associated with IPF, miR-326 (source \u2013 hAT-Tip100 DNAtransposon) and miR-1343 (source \u2013 LINE2 retrotransposon)originated from transposons, according to MDTE and dataof various authors . In 2015, Yang et al. identified significantchanges in the levels of 47 different miRNAs in the bloodplasma of IPF patients compared with healthy controls. Of these 47 microRNAs, 4 originatedfrom transposons: miR-31 (from LINE2), miR-302 (fromthe nonautonomous retroelement SINE/MIR), miR-335(from SINE/MIR), miR-374 (from LINE2) . These 47 microRNAs are involved in the signalingpathways of TGF-\u03b2, mitogen-activated protein kinase(MAPK), PI3K-Akt, Wnt, HIF-1, Jak-STAT, Notch, actincytoskeleton regulation . Reduced expressionof miR-630 ), miR-708-3p ) was detected in the bloodplasma of patients with IPF. Elevated levels of transposonderivedmiRNAs were shown for miR-487b (from SINE/MIR), miR-493 (from LINE2), miR-495 (from the LTRcontainingretroelement ERVL-MaLT) .MiR-340-5p, which promotes fibroblast proliferation in IPF byaffecting the ATF and MAPK/p38 pathways , originated from the TcMar-Mariner DNA transposon.Table 2 presents data on changes in the expression ofmiRNAs that originated in evolution from transposons (as wellas long non-coding RNAs (lncRNA)) in IPF with a comparativeanalysis of scientific literature data on these miRNAs inbronchial asthma and chronic obstructive pulmonary disease.As can be seen from Table 2, among 24 miRNAs, 13 of themare unique in the changes in expression in patients with IPF:miR-9-5p, miR-27b, miR-153, miR-184, miR-326, miR-340,miR-374, miR-424, miR-487b, miR-489, miR-493, miR-630,miR-1343. Of these, 8 microRNAs areevolutionarily derived from TE .Investigation of the role of epigenetic factors in thedevelopment of IPF serves as the basis for the developmentof new methods of targeted therapy for the disease. Potentialagents for the treatment of IPF may be non-coding RNAs.It was found that lncRNA PCAT29 (prostate cancer-associatedtranscript 29), which activates miRNA-221 and suppressesTGF-\u03b2, can be used to treat patients with IPF . It was discovered that expression of miR-506, whichis complementary to the 3\u2032-UTR of the p65 NF-\u03baB subunit, isdownregulated during IPF. Accordingly, the use of miR-506 asa target for targeted therapy may have an impact on apoptosisand inflammation in IPF . Administrationof antisense miR-21 reduced the severity of pathologyin mice with bleomycin-induced lung fibrosis, suggesting thepotential use of this miRNA in the treatment of IPF . Similar data were obtained for miR-708-3p. Overexpression of miR-184 suppressesTGF-\u03b2-induced fibrotic processes in the lung, thereforemiR-184 can be considered for targeted therapy of IPF . In animal experiments and in clinical studies onpatients with IPF, the effectiveness of the interfering sequencefor the long non-coding RNA lncITPF (sh-lncITPF), whichreduces the index of fibrosis, collagen and vimentin, wasalso revealed. In patients with IPF, an increased expressionof lncRNA-ITPF was revealed, which affects the acetylationof histones H3 and H4 in the promoter region of the ITGBL1gene, thus stimulating fibrosis. Transcription of lncITPF isunder the control of TGF-\u03b21/Smad2/3 .For IPF treatment, the DR8 peptide (DHNNPQIR-NH2),which has a powerful antioxidant activity, was proposed.In an animal experiment with bleomycin-induced IPF, it wasshown that after the use of DR8, fibrosis indicators, includingprofibrogenic and pro-inflammatory cytokines and markerproteins, were significantly reduced. DR8 reduced pathologicalchanges caused by bleomycin, as well as collagen deposits. In vivo experiments showed that DR8 isable to suppress the proliferation and generation of reactiveoxygen species stimulated by TGF-\u03b21 .Long non-coding RNAs (lncRNAs) are epigenetic factors,since they have transcriptional, post-transcriptional, and translationalregulatory effects on the functioning of the genome.This effect is realized both due to the secondary structure ofRNA, which provides interaction with proteins, and throughhybridization with DNA and RNA due to the complementarityof nucleotides. Many lncRNA genes evolved from transposons. According to the NONCODEv4database (http://www.noncode.org), more than 96,000 lncRNAgenes have been annotated in humans, many of which containTE sequences, which indicates the role of TEs in the origin oflncRNA genes . In addition, lncRNAcan be formed during the processing of transcripts of LTRcontainingretroelements or LINE retrotransposons. Analysis of GENOCODEand expressed RNA sequences showed that the majority oflncRNAs originated from transposons, since at least 83 % ofthem contain one or more retroelement fragments. On average,about 41 % of all lncRNA nucleotide sequences are identicalto transposons . Thus, changes in lncRNAexpression during IPF could indicate the role of transposonsin the pathogenesis of the disease. Indeed, in 2017, Hao et al.determined a decrease in the levels of 1,376 different lncRNAsand an increase in the levels of 440 lncRNAs in the bloodplasma of patients with ILF compared with healthy controls.The highest level was observed for lncRNA AP003419.16,which is involved in TGF-\u03b21 signaling pathways and can beused as a marker of disease . The above data indicate the role of transposons in the emergenceof noncoding RNAs that are involved in the pathogenesisof IPF and many other human diseases. The obtainedresults of molecular genetic studies of IPF are consistent withthis assumption. It refers to the influence of transposons on the aging processes that are involved in the pathogenesis of IPFand other multifactorial diseases .In aging, retrotransposons containing long terminal repeats and LINE1 are activated. Moreover, their overexpression during agingenhances the production of interferon, contributing to asepticinflammation in tissues .Transposons (due to the relationship with microRNAsderived from them) are involved in the functioning of theimmune system, the changes in which are associated with IPF. For example, the miR-31 microRNA derived fromLINE2 has a pro-inflammatory effect, enhancing the synthesisof IL-5,-8,-12, TNF-\u03b1 ; miR-302 (evolvedfrom SINE/MIR) increases production of IL-1\u03b2, IL-6, TNF-\u03b1. SINE/MIR are also a source of miR-487b,which represses IL-33 expression, reducing Ig-E levels. MiR-495 derived from ERVL-MaLTinhibits the synthesis of TNF-\u03b1, IL-1\u03b2, IL-6 . In mammalian evolution, RAG genes were domesticatedfrom ancient DNA transposons for V(D)J recombinationin the immune system. Vertebrate antigen-specific immunityhas two main features of DNA transposons. The componentsof immunity consist of recombinase (encoded by the RAG1and RAG2 genes) and mobile DNA (limited to specific sitesthat the recombinase recognizes). RAG proteins are homologousto Tc1-element transposase .LTR-containing retroelements are involved in the regulationof the human immune system, as they are enhancers for theHLA-G gene .Transposons also affect the sirtuins and TGF-\u03b2 involved in the pathogenesis of IPF. SIRT7 epigeneticallyrepresses LINE1 expression throughout the genome. Animportant role in this process is played by the interaction ofSIRT7 with lamins A/C, since SIRT7 ensures the deacetylationof histone H3K18, facilitating the interaction of LINE1with the nuclear lamina . Derived froman LTR-containing retroelement, the PEG10 gene encodesa PEG10-RF1 protein that interacts with members of theTGF-\u03b2 type I and II superfamily . The role ofevolutionarily young retroelements in the regulation of TGF-\u03b2pathways, along with PDGF, EGFR and p38 signaling, wasrevealed . The role of retroelements in theepithelial-mesenchymal transition important for the developmentof IPF was shown ,which is induced by the non-autonomous retrotransposon Aludue to the modulating of miR-566 expression . Telomere dysfunction leading to the development ofIPF and other diseases is likely associated with changes inthe activity of transposons, which are the evolutionary sourcesof genes involved in the functioning of telomeres and the telomerase gene .The investigation of epigenetic factors in the developmentof IPF is a promising direction in revealing the pathogenesisof the disease and developing more effective methods of itstherapy. Through the study of miRNAs, it was shown that IPF is associated with an imbalance in the epigenetic regulation ofthe genome. Therefore, the reason for the development of IPFmay be an imbalance in the control of the work of the genomeby dynamic structures that play a role in age-associatedpathology and aging of the body. The most appropriate controlelements are transposons, since they affect the functioning ofthe immune system and are closely related to it evolutionarily.It has been suggested that the study of the role of transposonsin the pathogenesis of IPF can reveal the pathways of themolecular cascade of the disease. Evidence for the role oftransposons in the pathogenesis of IPF is the evolutionaryemergence of long noncoding RNAs and miRNAs fromtransposons. Analysis of the MDTE database and scientificliterature revealed 12 specific IPF-associated miRNAs thatoriginated from transposons. 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Protective effect of peptide DR8 on bleomycin-induced pulmonary fibrosis by regulating the TGF-\u03b2/MAPKsignaling pathway and oxidative stress. Toxicol. Appl. Pharmacol.2019;382:114703. DOI 10.1016/j.taap.2019.114703.Wei G., Qin S., Li W., Chen L., Ma F. MDTE DB: a database formicroRNAs derived from transposable element. IEEE/ACM Trans.Comput. Biol. Bioinform. 2016;13(6):1155-1160. DOI 10.1109/TCBB.2015.2511767.Wei Y.Q., Guo Y.F., Yang S.M., Ma H.H., Li J. MiR-340-5p mitigatesthe proliferation and activation of fibroblast in lung fibrosis by targetingTGF-\u03b2/p38/ATF1 signaling pathway. Eur. Rev. Med. Pharmacol.Sci. 2020;24(11):6252-6261. DOI 10.26355/eurrev_202006_21523.Wyman A.E., Noor Z., Fishelevich R., Lockatell V., Shah N.G.,Todd N.W., Atamas S.P. Sirtuin 7 is decreased in pulmonary fibrosisand regulates the fibrotic phenotype of lung fibroblasts. Am. J.Physiol. Lung. Cell. Mol. Physiol. 2017;312:L945-L958. DOI10.1152/ajplung.00473.2016.Xiao L., Jiang L., Hu Q., Li Y. MiR-302e attenuates allergic inflammationin vitro model by targeting RelA. Biosci. Rep.2018;38(3):BSR20180025. DOI 10.1042/BSR20180025.Yang G., Yang L., Wang W., Wang J., Wang J., Xu Z. Discovery andvalidation of extracellular/circulating microRNAs during idiopathicpulmonary fibrosis disease progression. Gene. 2015;562:138-144.DOI 10.1016/j.gene.2015.02.065.Zhang Y.F., Gu L.N., Qi J., Xia Q.Q., Tian L.J., Jiang W.L., Cao M.S.Construction of potential idiopathic pulmonary fibrosis related micro-RNA and messenger RNA regulatory network. Chin. Med. J. (Engl).2021;134(5):584-586. DOI 10.1097/CM9.0000000000001276.Zhao J., Ren Y., Qu Y., Jiang W., Lv C. Pharmacodynamic and pharmacokineticassessment of pulmonary rehabilitation mixture forthe treatment of pulmonary fibrosis. Sci. Rep. 2017;7:3458. DOI10.1038/s41598-017-02774-1.Zhu L., Wang L., Luo X., Zhang Y., Ding Q., Jiang X., Wang X.,Pan Y., Chen Y. Tollip, an intracellular trafficking protein, is a novelmodulator of the transforming growth factor-\u03b2 signaling pathway.J. Biol. Chem. 2012;287(47):39653-39663. DOI 10.1074/jbc.M112.388009.Zhu M., An Y., Zhang X., Wang Z., Duan H. Experimental pulmonaryfibrosis was suppressed by microRNA-506 through NF-kappa-mediatedapoptosis and inflammation. Cell. Tissue Res. 2019;378:255-265. DOI 10.1007/s00441-019-03054-2."} +{"text": "Milnesium Doy\u00e8re, 1840 is particularly difficult because in comparison with most other eutardigrades, the genus lacks the taxonomically informative egg shell ornamentation and/or placoids in the muscle pharynx. Therefore, any new morphological traits that could be used in species delineation and identification are priceless. In this contribution, we review and evaluate taxonomic value of the dorsal cuticle morphology. Specifically, by means of experimental taxonomy, we demonstrate the first extreme case of ontogenetic variability in dorsal epicuticle sculpturing using a new species from Portugal, Milnesium decorumsp. nov. Furthermore, we verify the existence of dorsal gibbosities in Milnesium reticulatum Pilato, Binda, Lisi, 2002, the only species of the genus allegedly exhibiting these structures. Finally, we provide a diagnostic key to the Milnesium granulatum morphogroup.The phylum Tardigrada comprises\u2009~\u20091400 described species that inhabit a wide range of ecosystems throughout the globe. Tardigrades are generally considered taxonomically challenging due to a strongly limited number of taxonomically informative morphological traits and microscopic size. Of all tardigrade groups, the taxonomy of These ubiquitous invertebrates inhabit almost all environments on our planet, both terrestrial and aquatic, however, to be active they require at least a water film2. Tardigrades, commonly named as water bears, are well-known for their ability to enter cryptobiosis and withstand harsh environmental conditions3. To date almost 1400 species have been formally described4 and this number is systematically growing. Tardigrades can feed on various food sources5, but only one group\u2014the order Apochela\u2014is considered exclusively carnivorous, as it can survive and reproduce only by hunting for rotifers, nematodes, protozoans or other tardigrades7. This order, comprising a single family Milnesiidae, is taxonomically challenging due to the low number of taxonomically meaningful morphological traits and still scarce integrative data . The family comprises four genera, three monotypic and one, Milnesium Doy\u00e8re, 18409, which groups 44 valid extant species. However, recent surveys showed that the described species constitute a small fraction of the true species diversity10.The phylum Tardigrada groups microscopic eight-legged animals belonging to the superclade EcdysozoaMilnesium into multiple genera10, the genus can be divided into morphogroups that gather species exhibiting the same or similar states of morphological traits regardless of the phyletic relationships between these species. Morphogroups are useful for practical taxonomic reasons, such as constructing differential diagnoses or diagnostic keys. The two main traits used for the delineation of morphogroups in Milnesium are claw configuration (CC) and dorsal cuticle surface12. The CC informs about the number of points on secondary branches of claws and their position on fore- and hindlimbs, and there are currently seven recognised CC morphotypes14. In parallel, the dorsal cuticle sculpture allows for dividing Milnesium species into two morphogroups, the tardigradum and the granulatum morphogroup, clustering species with cuticle appearing in light microscopy as smooth or reticulated, respectively.Although there is weak correlation between taxonomically important traits and phylogeny, which prevents splitting vs non-reticulated cuticle seems straightforward, phase contrast microscopy (PCM) observations of cuticular surface in Milnesium proved to be misleading. In fact, the first described species with the epicuticular reticulum, Milnesium granulatum Ramazzotti, 196215, was thought to have the dorsal cuticle covered with granulation. Ramazzotti15 interpreted bright polygons on the cuticle surface as granules (hence the species\u00a0and the morphogroup\u00a0name). This is surprising because granules, being thicker than the surrounding cuticle, always appear darker in PCM; thus, bright polygons must be areas where the cuticle is thinner. Indeed the first scanning electron microscope (SEM) observations of another species exhibiting the same cuticle morphotype, Milnesium krzysztofi Kaczmarek & Michalczyk, 200716, showed that \u201cgranules\u201d are depressions, which form a reticular system of meshes delineated by polygonal epicuticular ridges16. Soon after the tardigradum and the granulatum morphogroups were defined, Milnesium beasleyi Kaczmarek et al., 201217, a species with minute but evident and densely arranged bright spots with blurred edges was discovered. Similar spots were identified in the heterotardigrade Barbaria madonnae Michalczyk & Kaczmarek, 200618 and SEM analysis showed that the reason why the edges cannot be focused in PCM is that they are shallow epicuticular depressions. Thus, to differentiate them from true pores that pierce the epicuticle and hence have well-defined and focusable edges, Michalczyk & Kaczmarek18 termed such depressions as pseudopores. Since spots in M.\u00a0beasleyi appeared under PCM similar to spots in B. madonnae, Kaczmarek et al.17 interpreted them as pseudopores and classified M.\u00a0beasleyi as a member of the granulatum morphogroup. However, subsequent analyses of M. tardigradum Doy\u00e8re, 18409 in high quality light and scanning electron microscopy showed that pseudopores are endocuticular channels19. In fact, these channels were first discovered via transmission electron microscopy (TEM) observations by Greven20, but they were never linked to pseudopores observed in PCM before. Probably all members of the genus have these structures, but their diameter and number differs between species, which translates to their variable visibility under light microscopy21. Thus, since pseudopores are not epicuticular structures, Morek et al.19 postulated to restore the original definition of the granulatum morphogroup, that is, restrict it to species with epicuticular reticulation. Currently, the morphogroup comprises eight species : M. granulatum; M.\u00a0reticulatum Pilato, Binda, Lisi, 200222; M. katarzynae Kaczmarek et al., 200423; M. krzysztofi; M. alabamae Wallendorf & Miller, 200924; M.\u00a0lagniappe Meyer, Hinton & Dupr\u00e9, 201325; M.\u00a0cassandrae Moreno-Talamantes et al., 201926; and M. pacificum Sugiura et al., 202027. In one of these species, M.\u00a0reticulatum, additionally to the epicuticular reticulum, dorsal cuticular gibbosities were also described, although only a drawing and no photographic evidence of this unique trait was provided in the original description, and the species has not been recorded ever again.Although the criterion of reticulated Milnesium. The description of a new species representing the granulatum morphogroup and a discovery of a novel cuticle morphotype provide an occasion to revise this morphogroup, including the verification of the presence of gibbosities in M. reticulatum via the re-examination of the type material. Finally, we construct a new diagnostic key to the discussed morphogroup.In this study, we address several aspects of the cuticle morphology and its taxonomic value in the genus 28 from a moss sample collected in Portugal DNA extraction and sequencing. The exact number of specimens utilised for given analysis is provided in Table Individuals representing the new species were extracted according to procedures described in29 to examine general morphology in PCM and acquire morphometric data. The measurements follow30, the buccal tube widths were measured according to12 and the body length was measured from the anterior to posterior margin of the body, excluding the hind legs. Pseudoplate row numbers are given according to26 and poorly visible pseudoplates are marked with a dotted line. The pt index is a ratio of a given structure to the length of the buccal tube, expressed as a percentage31 and in the text is given in italics. The number of measured specimens follow the recommendation of32 when it was possible, otherwise all available and properly fixed and oriented specimens were measured. Structures were measured only if their orientation was suitable. We present the joined measurements of specimens of the same CC (i.e. juveniles and adults) in a single table. The morphometric data was handled using the Apochela spreadsheet ver. 1.3. available from Tardigrada Register33, www.tardigrada.net. All the measurements and photographs were taken with Olympus BX53 PCM associated with Olympus DP74 digital camera (PCM). Pseudoplate arrangement was additionally determined with the UVM Nikon Eclipse 80i associated with Nikon Digital Sight DS-L2 digital camera34. For deep-focus structures a series of up to 22 pictures were taken and merged into one image using Corel Photo-Paint 2020. Some specimens were processed for SEM imaging according to the protocol by28 and examined under high vacuum with a Versa 3D DualBeam Scanning Electron Microscope at the ATOMIN facility, of the Jagiellonian University, Krak\u00f3w, Poland.The specimens were mounted on permanent microscope slides in Hoyer\u2019s medium according to the method byt-tests to demonstrate statistically significant differences between pairs of species with slightly overlapping ranges of morphometric traits.In the differential diagnosis, we used two tailed Student 35 with rotifers Lecane inermis Bryce, 189236, as a food source. To test for ontogenetic variability, developmental tracking13 was applied.Culture of the new species was established from alive specimens and eggs deposited in exuviae. The culture was incubated at rearing conditions described byChelex\u00ae 100 resin (Bio-Rad) extraction method by37, with modifications by38. Prior to the DNA extraction, the specimens were mounted on temporary water slide to check the morphology (CC). The four standard molecular markers were sequenced, three nuclear: the small ribosomal subunit (18S rRNA), large ribosomal subunit (28S rRNA), Internal Transcribed Spacer 2 (ITS-2); and one mitochondrial, Cytochrome Oxidase C subunit I (COI). The PCR protocols follow38, primers and PCR programmes with relevant references are listed in Table 46. In addition the COI sequences were translated into amino acids using MEGA\u00a0747 to ensure that no pseudogenes were amplified. All sequences are deposited in GenBank ; TR/t1/3; TR/t1/11); M.\u00a0katarzynae Kaczmarek, Michalczyk & Beasley, 200423 (slide no.: 13/2); M.\u00a0krzysztofi Kaczmarek & Michalczyk, 200716 and M.\u00a0reticulatum Pilato, Binda, Lisi, 200222 (slide no.: 4855).For the comparisons with the new species, we examined slides from type series of M.\u00a0decorumsp. nov. are provided as supplementary materials and are also deposited in the Tardigrada Register33 under www.tardigrada.net/register/0116.htm. DNA sequences are deposited in GenBank , the reticulation may be poorly visible in PCM and six triangular peribuccal lamellae of unequal size of Hoyer-fixed specimens. Cuticular bars under claws always absent .In the sample only single male was found (preserved on SEM stub) but the culture yielded additional 10 specimens. Smaller than females Fig.\u00a0H, as in Morphologically similar to adult females but with a better developed dorsal reticulation and more weakly outlined dorsal pseudoplates Fig.\u00a0B. Eyes pMorphologically similar to juveniles but with a better developed dorsal reticulation and more weakly outlined dorsal pseudoplates Fig.\u00a0A. All seMilnesium decorumsp. nov. undergoes developmental changes in two key taxonomic traits, cuticular sculpturing and CC. The dorsal cuticle sculpturing becomes less clear with every consecutive instar. Specifically, under PCM, it is most pronounced in hatchlings, slightly less developed in juveniles, and it is very weakly outlined in adults or even not visible at all in large adult females. Under SEM, the reticulum also fades with subsequent moults, but it is detectable in all life stages , 28S\u00a0rRNA: 801\u00a0bp (MK483983), ITS-2: 489\u00a0bp (MK484010), and COI: 559\u00a0bp (MK492287). The new species represents the Palaearctic clade A sensu38\u00b041\u203224\u2033N, 9\u00b019\u203218\u2033W, 27\u00a0m asl: Portugal, Lisbon District, Oeiras, Conde Oeiras Lane; lichen on a tree branch; city.dec\u014drus\u2009=\u2009decorated, beautiful.The name of the species highlights the pronounced dorsal cuticle sculpturing in hatchlings and juveniles, composed of epicuticular reticulation and endocuticular pseudoplates. From Latin The series consists of the holotype and 40 paratypes, 32 on microscope slides (PT.010.39\u201365) and 8 on an SEM stub (10.09). All slides and the SEM stub are deposited at the Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30\u2013387 Krak\u00f3w, Poland.Milnesium sp. from the almatyense complex (Milnesium sp. #5 PT.010 A in8), which was much more abundant in the sample. All of the 26 eggs of M. decorumsp. nov. incubated in the laboratory culture hatched, and nine hatchlings and seven juveniles were fixed on microscope slides. All remaining ten juveniles kept in the culture eclosed into males. Thus, with no adult females obtained in the laboratory, the culture was terminated. As a result, most of the type series consists of hatchlings and males. Because of that, the type series contains small number of mature females, which are in addition poorly to moderately preserved, thus as a result we designated a juvenile as the holotype.The species was accompanied with a Milnesium decorumsp. nov. is one of the 13 described species of Milnesium characterised by a [2-3]-[3-2] adult CC, and can be differentiated specifically from:M.\u00a0barbadosense Meyer & Hinton, 201250; M.\u00a0pseudotardigradum Surmacz, Morek & Michalczyk, 201951; M.\u00a0reductum Tumanov, 200630; M.\u00a0tardigradum Doy\u00e8re, 18409; M.\u00a0tetralamellatum Pilato & Binda, 199152 and M.\u00a0vorax Pilato, Sabella & Lisi, 201653; by the well-visible nine rows of pseudoplates vs invisible or poorly visible just an outline of single pseudoplate (row VIII) in the remaining species.M.\u00a0beasleyi Kaczmarek, Jakubowska & Michalczyk, 201217, known only from type locality in Turkey, by the relatively shorter lateral papillae , the cuticular sculpture (well-visible reticulum in PCM in juveniles vs pseudoporous cuticle lacking reticulum in M.\u00a0beasleyi).M.\u00a0lagniappe Meyer, Hinton & Dupr\u00e9, 201325; recorded from the United States, by a relatively more anterior stylet support insertion point (SSIP) (59.2\u201365.6 in the new species vs 69.7\u201373.4 in M.\u00a0lagniappe) and by a relatively shorter primary claw branch IV (49.3\u201361.7 in the new species vs 62.9\u201376.6 in M.\u00a0lagniappe).M.\u00a0krzysztofi Kaczmarek & Michalczyk, 200716, reported from Costa Rica and Peru54, by the appearance of the dorsal reticulum .M.\u00a0cassandrae Moreno-Talamantes et al., 201926, found only in several localities in Mexico, by a relatively narrower standard buccal tube width (25.5\u201328.7 in the new species vs 41.6\u201367.2 in M.\u00a0cassandrae) and by a different direction of the ontogenetic CC change (negative in the new species vs positive in M.\u00a0cassandrae).M. pacificum Sugiura, Minato, Matsumoto & Suzuki, 202027, reported from three islands of Japan, by the relatively longer spurs on claws I and II (11.3\u201313.8 on claws I and 12.2\u201318.7 on claws II in the new species vs 5.3\u201311.7 on claws I and 6.0\u201312.2 on claws II in M.\u00a0pacificum) and by a different pattern of the ontogenetic CC change (negative in the new species vs positive in M.\u00a0pacificum).M. reticulatum Pilato, Binda & Lisi, 200222, known only from the Seychelles, by a relatively more anterior stylet support insertion point (SSIP) (59.2\u201365.6 in the new species vs 68.5\u201369.8 in M.\u00a0reticulatum) and by a relatively longer primary claw branch IV (49.3\u201361.7 in the new species vs 37.9\u201344.3 in M.\u00a0reticulatum).Milnesium decorumsp. nov. hatchlings differ from the two described species with a [3-3]-[3-3] CC and reticulated cuticle:M. alabamae Wallendorf & Miller, 200924, recorded only from USA (Alabama), by a relatively narrower standard buccal tube width .M. granulatum Ramazzotti, 196215, known only from Chile (the only confirmed record), by a relatively narrower standard buccal tube width .18S rRNA: 1.0\u20133.2% (2.2% on average), with the most similar being M.\u00a0dornensis Ciobanu, Roszkowska & Kaczmarek, 201555 (MK48407110), and the least similar being unidentified species from Australia (MK484082/\u201cMilnesium sp. nov. 13 AU.052 B\u201d in10).28S rRNA: 2.2\u201310.5% (7.2% on average), with the most similar being an unidentified species from Canary Island, Spain (MK483995/\u201cMilnesium sp. nov. 2 ES.012\u201d in10) and the least similar being an unidentified species from the Philippines (MK484004/\u201cMilnesium sp. nov. 10 PH.014\u201d in10).ITS-2: 8.4\u201320.6% (13.0% on average), with the most similar being an unidentified species from Canary Island, Spain (MK484020/\u201cMilnesium sp. nov. 2 ES.012\u201d in10) and the least similar being an unidentified species from Australia (MK484015 and MK484018/\u201cMilnesium sp. nov. 11 AU. 52 A and AU.105\u201d in10).COI: 11.2\u201322.3% (16.0% on average), with the most similar being M.\u00a0dornensis (MK48407119), and the least similar being an unidentified species from Australia (MK492295/\u201cMilnesium sp. nov. 11 AU.105\u201d in10).The ranges of uncorrected p-distances between the new species and available sequences for other congeners are as follows:M. reticulatum paratypes under PCM confirmed that the dorsal cuticle is covered with a distinct and robust reticulum, similar to that in M.\u00a0krzysztofi . However, in contrast to the original description22, which states that \u201c7 transversal rows of not very prominent gibbosities are present [on the dorsum]\u201d, we saw no gibbosities on the dorsal cuticle of M.\u00a0reticulatum. Instead, we observed poorly outlined pseudoplates, which were misinterpreted as gibbosities in the original description . Due to poor preservation of the examined specimens, the determination of the exact pseudoplate arrangement was not possible.The re-examination of four M. reticulatum from all other known congeners, but now this traits has been invalidated, the validity of similar species published after the description of M.\u00a0reticulatum needs to be verified. In addition to M.\u00a0reticulatum, there are only five other known Milnesium species with a [2-3]-[3-2] CC and reticulated dorsal cuticle: M.\u00a0cassandrae, M. decorumsp. nov., M.\u00a0krzysztofi, M. lagniappe and M.\u00a0pacificum. These species all differ from M.\u00a0reticulatum by relative morphometric traits, specifically by the pt of the SSIP and by the pt of the anterior primary claw branch height . Therefore, the amendment of M.\u00a0reticulatum description does not entail any changes in the taxonomic status of other congeners.Given that the gibbosities alone were sufficient to differentiate M.\u00a0reticulatum highlights the importance of providing the readers with raw data, such as photomicrographs, as this is the only way the scientific community may widely and at any time evaluate the interpretation and conclusions laid out by the authors of the original contribution . In22, all images, including the dorsum and the alleged gibbosities, are in the form of drawings, thus the reader is presented only with an interpretation. It has been demonstrated that morphological interpretations may vary considerably between researchers56 and the original description of M.\u00a0reticulatum is a striking example of this phenomenon. Another misinterpretation of Milnesium morphology was recently exposed by57 who showed that the alleged three spines on the dorsum of the invalid now \u201cMilnesium tardigradum trispinosa\u201d58 were, in fact, folds of the cloacal cuticle. Have there been photographs of these structures provided in the original contributions, the scientific community most likely would have falsified them earlier. Thus, although drawings can be a useful addition to photomicrographs in tardigrade taxonomy, they should not be the only mean of morphological illustration.The original description of Milnesium species, the dorsal cuticle surface can be divided into two main morphotypes when observed under the light contrast microscope (LCM): smooth and reticulated . These two morphogroups have been named after the first described species exhibiting given morphotype, i.e. the tardigradum . Furthermore, these can be split into subgroups. Specifically, some species of the tardigradum morphogroup have weakly . In other words, we are of the opinion that the species should be described only when more individuals are found and their DNA is sequenced .However, as more new species in the genus are uncovered, new types of cuticular sculpturing may be revealed. In fact, we have found such a new morphotype represented by an undescribed species collected in Colombia . Moreover,13 suggested that the number, shape and arrangement of these structures could possibly be used for species delineation and identification, but this view was questioned by26, who hypothesised that pseudoplates do not exhibit variation within the genus and therefore should not be used as a taxonomic trait. However, our extensive analysis of numerous species, some represented by multiple populations, under both PCM and UVM showed that there are species, such as M. tardigradum . However, there are two species in which ontogenetic variability in the epicuticular sculpturing has been observed: M. pacificum27 and M. decorumsp. nov. (the present study). In both these species, the reticulation is most developed in hatchlings and it becomes weaker with each consecutive instar, but the differences between the life stages are more pronounced in the latter taxon. Given that ontogeny has been investigated only in a small fraction of species, more research is needed to draw more general conclusions about the frequency and direction of developmental variability in cuticle appearance. Although the analysis of ontogenetic variability makes species descriptions more difficult, on the other hand, it provides extra characters for species delineation and identification in this taxonomically challenging genus.In the great majority of granulatum morphogroup is defined here as a polyphyletic group of Milnesium species in which cuticular reticulation on the dorsal cuticle is visible under LCM at least in one life stage (i.e. in hatchlings [H] and/or juveniles [J] and/or adults [A]). The morphogroup currently comprises 9 formally described species (20% of the known Milnesium species). Morphometric data in the key refer to sexually immature and mature individuals collectively.1. Claw configuration [2\u20132]-[2\u20132] ........................................................................................... (2)\u2013. Different claw configuration .............................................................................................. (4)2. The pt values of the stylet support insertion point above 73 ................... M. katarzynae [H*]\u2013. The pt values of the stylet support insertion point below 73 ............................................. (3)3. Buccal tube below 23.0\u00a0\u00b5m ....................................................................... M. cassandrae [H]\u2013. Buccal tube above 23.0\u00a0\u00b5m ........................................................................ M. pacificum [H]4. Claw configuration [2\u20133]-[3\u20132] ........................................................................................... (5)\u2013. Claw configuration [3\u20133]-[3\u20133] ........................................................................................... (9)5. Four peribuccal lamellae present ........................................................................................ (6)\u2013. Six peribuccal lamellae present .......................................................................................... (7)6. The pt values of the anterior primary branches below 45 ................... M. reticulatum [H\u2009+\u2009J*]\u2013. The pt values of the anterior primary branches at least 55 ................. M. lagniappe [H\u2009+\u2009J\u2009+\u2009A]7. The reticulum thin-walled and very regular ................................ M. decorumsp. nov. [J\u2009+\u2009A]\u2013. The reticulum thick-walled and mostly irregular ................................................................ (8)8. The pt values of the buccal tube standard width at least 47 .................. M. cassandrae [J\u2009+\u2009A]\u2013. The pt values of the buccal tube standard width lower than 47 ..............................................M. krzysztofi [J\u2009+\u2009A*]and M. pacificum [J\u2009+\u2009A]\u2020........................................................................... 9. Primary branches without accessory points ....................................... M. alabamae [H\u2009+\u2009J\u2009+\u2009A]\u2013. Primary branches with accessory points .......................................................................... (10)10. The pt values of the buccal tube standard width higher than 35 ........... M. granulatum [A*]\u2013. The pt values of the buccal tube standard width lower than 35 ..... M. decorumsp. nov. [H]*The original description of the species is most likely based only on the indicated life stage(s)\u2020The two species are phenotypically indistinguishable based on original descriptionsThe Milnesium. The new species, M. decorumsp. nov., represents the granulatum morphogroup and is the most striking example of ontogenetic variability in epicuticular sculpturing to date. We also amended the description of M. reticulatum, demonstrating that gibbosities are not present in any of the known Milnesium species. Moreover, our study showed that more research is needed to clarify the types of fine epicuticular sculpturing that are identifiable only under SEM, but appear as smooth cuticle under LCM. Further studies should also address the taxonomic value of pseudoplate number, shape and arrangement. Finally, the lack of evidence for phenotypic differences between M. krzysztofi and M. pacificum, noted when constructing the diagnostic key, calls for an integrative redescription of the senior species and is a reminder that utmost care must be takes when differentiating new and described Milnesium species.We have integratively described the 45th species of the genus Supplementary Information."} +{"text": "Scientific Reports 10.1038/s41598-022-14755-0, published online 27 June 2022Correction to: The original version of this Article contained errors in the spelling of the authors Cosmin Andrei Cismaru, Sergiu Chira, Gabriel Laurentiu Cismaru, Andreea Mihaela Nutu, Mihai Gheorghe Netea and Ioana Berindan-Neagoe, which were incorrectly given as Cismaru Cosmin-Andrei, Chira Sergiu, Cismaru Gabriel-Laurentiu, Nutu Andreea-Mihaela, Netea Mihai-Gheorghe and Berindan-Neagoe Ioana.The Author contribution statement now reads:\u201cC.A.C. performed the study concept and design. C.A.C., S.C. and A.M.N. performed the sampling and acquisition of data. G.L.C. performed the data analysis. All authors contributed to interpretation of data and revision of the report. I.B-N. and M.G.N. have been involved in drafting the manuscript and revising it critically for important intellectual content.\u201dThe original Article has been corrected."} +{"text": "EML4\u2013ALK variant 2 (E20:A20), wild-type TP53/RB1, and low tumor mutational burden of 3.91 mut/Mb. Despite early progression within 3 mo under crizotinib, a durable response was achieved with alectinib. Oligoprogression in the left breast 10 mo later was treated by surgery, followed by a switch to ceritinib upon multifocal progression and detection of ALK:p.V1180L in the mastectomy specimen, but without success. Another rebiopsy revealed ALK:p.L1196M, but the tumor did not respond to brigatinib or carboplatin/pemetrexed, before stabilization under lorlatinib. Diffuse progression 8 mo later with detection of ALK:p.L1196M/p.G1202R and p.L1196M/ p.D1203N evolving from the previous p.L1196M did not respond to chemoimmunotherapy, and the patient succumbed with an overall survival (OS) of 37 mo. This case illustrates the importance of molecular profiling for LCNEC regardless of smoking status, and the superiority of next-generation ALK inhibitors compared to crizotinib for ALK+ cases. Lorlatinib retained efficacy in the heavily pretreated setting, whereas its upfront use could possibly have prevented the stepwise emergence of compound ALK mutations. Furthermore, the disease course was more aggressive and OS shorter compared to the V2/TP53wt ALK+ lung adenocarcinoma, whereas crizotinib, ceritinib, and brigatinib did not confer the benefit expected according to next-generation sequencing results, which also underline the need for more potent drugs against ALK in the high-risk setting of neuroendocrine histology.Large-cell neuroendocrine lung carcinoma (LCNEC) is a high-grade neoplasm with median survival of 1 year and limited therapeutic options. Here, we report the unusual case of a 47-yr-old female smoker with stage IV LCNEC featuring Large-cell neuroendocrine lung carcinomas (LCNECs) are rare, high-grade neoplasms with poor survival and very limited therapeutic options . They reALK) fusions drive \u223c5% of lung adenocarcinomas (ALK fusion variant and TP53 status (EML4)-ALK fusions were first described in lung cancer of the chest/abdomen and brain magnetic resonance imaging (MRI) revealed metastatic lesions to multiple mediastinal lymph nodes, the liver, and the right adrenal gland, as well as three small (up to 5 mm) asymptomatic supratentorial lesions in the right cerebral hemisphere A. A bronALK:p.V1180L mutation. Consequently, upon multifocal disease progression 3 mo later, alectinib was switched to ceritinib, but no tumor response was noted. Histological and molecular analysis of a growing chest wall lesion revealed ALK:p.L1196M. Consequently, the patient was switched to brigatinib, but showed further tumor growth under this drug, as well as under the subsequently administered carboplatin-pemetrexed chemotherapy, before achieving disease stabilization with lorlatinib, which lasted for \u223c8 mo. In February 2020, tumor growth was noted again at several sites, along with detection of ALK:p.L1196M/p.G1202R and p.L1196M/p.D1203N compound mutations in the regions covered by our 38\u201342-gene panel panel, which covers all TP53 and RB1 exons, including splice sites, as well as sensitive detection of copy-number variations, and showed no mutation or deletion of these two genes revealed the presence of an oncogenic gene fusion between and RB1 . A lung eritinib . Analysiigatinib . In addihat time , which ihat time . Analysirlatinib . The comp.G1202R C. Given rlatinib . All fivne panel ; in partwo genes . The TSOwo genes . The resALK fusions in two large series: 0/43 patients and/or TP53 mutations, whereas EML4\u2013ALK v2 TP53wt adenocarcinomas show a more indolent course and have a longer OS (TP53wt cases) within the first 6 mo. Such an early dissemination is typical for the presence of onger OS . Therefoonger OS versus >onger OS . Similaronger OS . In keeponger OS , but higt cases) . Thus, Ase drugs . One molrebiopsy , which pg cancer .TP53wt and RB1wt status of the tumor, which suggest that the tumor may have an \u201cNSCLC-like\u201d biology .Immunohistochemical staining was conducted using an autostainer according to the manufacturer's instructions sections of each sample by applying the Maxwell 16 FFPE Tissue LEV DNA Puri\ufb01cation Kit on a Maxwell 16 Research system (both Promega). DNA concentrations were determined with the Qubit HS DNA assay (Thermo Fisher Scienti\ufb01c) according to the manufacturers\u2019 protocols.Supplemental Tables 2 and 3. Mutation and CNV calling was completed by GATK 4.2. Fusion detection was performed from the RNA-seq panel as published (https://github.com/chrisamiller/fishplot) (A 38/42-gene custom DNA and RNA panel (Thermo Fisher Scienti\ufb01c) was used for targeted sequencing on the IonTorrent platform according to the manufacturers protocol as previously described . The covublished . Clonal ublished and plotishplot) . Hybrid-https://www.ncbi.nlm.nih.gov/clinvar/) with the accession numbers SCV002571104\u2013SCV002571107, as shown in Mutations in Written consent was obtained from the patient included in this study. Ethical approval for the study was granted by the ethics committee of Heidelberg University (S-296/2016). The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013).CSH Molecular Case Studies.C.W., J.K., D.K., and P.C. conceptualized the study. M.Ki., M.Kr., D.K., D.F., H.S., C.-P.H., A.S., and P.C. established the methodology. C.W., J.K., M.Kr., D.K., D.F., C.-P.H., and P.C. analyzed the data. C.W., D.F., C.-P.H., and P.C. interpreted the data. C.W., H.B., M.T., A.S., and P.C. provided resources. P.C., J.C., and C.W. wrote the original draft. All authors reviewed the writing and edited the manuscript. C.W., D.K., J.C., M.Kr., C.-P.H., and P.C. visualized the project. M.T., A.S., and P.C. supervised the project. All authors have approved the current version of the manuscript and its submission to This research received funding from the German Center for Lung Research (DZL).C.W. reports speaker\u2019s honoraria from GSK, Roche, and the German Society of Pneumology, as well as advisory board fees from Roche and educational fees from MSD and Boehringer Ingelheim. D.K. reports personal fees from AstraZeneca, Bristol-Myers Squibb, Pfizer, Lilly, Agilent, and Takeda outside the submitted work. A.S. reports advisory board honoraria from BMS, Astra Zeneca, Thermo Fisher, and Novartis; speaker\u2019s honoraria from BMS, Illumina, Astra Zeneca, Novartis, Thermo Fisher, MSD, and Roche; and research funding from Chugai and BMS. M.T. reports advisory board honoraria from Novartis, Eli Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer Ingelheim, and Pfizer; speaker\u2019s honoraria from Eli Lilly, MSD, Takeda, and Pfizer; research funding from Astra Zeneca, BMS, Celgene, Novartis, Roche, and Takeda; and travel grants from BMS, MSD, Novartis, and Boehringer. P.C. reports research funding from Amgen, Astra Zeneca, Boehringer Ingelheim, Merck, Novartis, Roche, and Takeda; and advisory board/lecture fees from Astra Zeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, and Takeda. All other authors have no conflict of interest to declare."} +{"text": "L-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the food and pharmaceutical industries, medicine and cosmetics, but primarily as an animal feed additive. Adding L-valine to feed, alone or mixed with other essential amino acids, allows for feeds with lower crude protein content, increases the quality and quantity of pig meat and broiler chicken meat, as well as improves reproductive functions of farm animals. Despite the fact that the market for L-valine is constantly growing, this amino acid is not yet produced in our country. In modern conditions, the creation of strains-producers and organization of L-valine production are especially relevant for Russia. One of the basic microorganisms most commonly used for the creation of amino acid producers, along with Escherichia coli, is the soil bacterium Corynebacterium glutamicum. This review is devoted to the analysis of the main strategies for the development of L- valine producers based on C. glutamicum. Various aspects of L-valine biosynthesis in C. glutamicum are reviewed: process biochemistry, stoichiometry and regulation, enzymes and their corresponding genes, export and import systems, and the relationship of L-valine biosynthesis with central cell metabolism. Key genetic elements for the creation of C. glutamicum-based strains-producers are identified. The use of metabolic engineering to enhance L-valine biosynthesisreactions and to reduce the formation of byproducts is described. The prospects for improving strains in termsof their productivity and technological characteristics are shown. The information presented in the review can be usedin the production of producers of other amino acids with a branched side chain, namely L-leucine and L-isoleucine, aswell as D-pantothenate. L-Valine is a proteinogenic branched-chain amino acid (BCAA),which also include L-leucine and L-isoleucine . These are essentialamino acids that are not synthesized in humans or animalsand must be present in the diet. Therefore, these amino acidsare mainly used in the animal feed industry and as a dietarysupplement for humans . The formeris particularly relevant to the global task of intensifyinglivestock production. Adding valine to feeds, either aloneor mixed with other BCAAs, leads to improved meat qualityand quantity in pigs and broiler chickens, increased eggproduction in chickens, increased lactation, milk fat contentand appetite in pigs . A balancebetween different BCAAs, however,must be maintained, as its disruption can reduce the observedbeneficial effects .In addition to the livestock and food industries, BCAAsfind their application in pharmacology and medicine. BCAAsnot only serve as building blocks for proteins, but also participatein the regulation of protein and energy metabolism,their consumption increases exercise tolerance and acceleratesfatty acid oxidation . They areuseful as supplements for chronic liver disease and for stimulating macrophage phagocytosis ofmultidrug-resistant bacterial pathogens .As with feed additives, when using BCAAs for food and drugproduction their concentration should be chosen carefully.Excess BCAA in human plasma increases the risk of severaldiseases, including type 2 diabetes, metabolic syndrome,obesity, hypertension, and cardiovascular disease , but has little effect on athletes whoare characterized by high physical activity .Amino acids account for 62.3 % of the global feed supplementmarket, which is projected to be $34.2 billion in 2022.L-lysine and L-methionine are the most in demand; the valine market is oneof the fastest growing, along with L-threonine (hereinafterreferred to as threonine) and L-tryptophan. Consumption offeed amino acids is concentrated in Europe, USA and China;Russia\u2019s share is less than 2 %, but shows a growing trend:from 2016 to 2017 the increase was 2.9 % . Currently, all valine onthe Russian market is imported from China, one of the mainproducers of this amino acid.Amino acids can be isolated from natural protein sources,obtained by chemical synthesis, as well as by a microbiologicalmethod based on the use of strain-producers. The latteroption has important advantages: it allows to use renewableraw material resources and to produce biologically activeL-enantiomersof amino acids separately, rather than mixedwith D-enantiomers, and is therefore used by leading valineproducers .Amino acid producers are developed from Escherichiacoli and Corynebacterium glutamicum. E. coli is a thoroughlystudied bacterium for which an extensive toolkit of geneticmodification is available. Due to that fact producer strains werepreviously derived mainly from E. coli. However, strains ofC. glutamicum created by selection were also used. The historyof their use for amino acid production goes back morethan 60 years . In recent decades,having made considerable progress both in understanding themetabolism of C. glutamicum and in improving methods formodifying their genome, developers of producer strains haveincreasingly begun to favor Corynebacteria.Corynebacteria are nonpathogenic, GC-rich gram-positivebacteria, which, unlike E. coli, do not form endotoxins thatcause allergic reactions in higher organisms. They are alsocharacterized by flexible cellular metabolism, genetic stability,stress tolerance, including resistance to high concentrations ofcarbon sources and metabolites, and the ability to synthesizethe target product when growth stops .Valine produced by fermentation using C. glutamicum strainsis now recognized as safe (non-toxic and non-carcinogenic)for use as a food and feed additive and for other biologicalpurposes .This review presents the main strategies for increasingvaline production by C. glutamicum cells. It also summarizesthe achievements in the creation of valine-producing strains.In addition to obtaining valine, some aspects of obtainingisoleucine, leucine, and D-pantothenate are also discussed because the biosynthesis of thesecompounds involves the same metabolic precursors, cofactors,and enzymes as does valine biosynthesis.Valine (2-amino-3-methylbutyric acid) is synthesized frompyruvate (pyruvic acid) through four consecutive reactionsinvolving : 1) condensation of two pyruvate moleculesto form acetolactate, catalyzed by acetolactate synthase(AHAS); 2) NADPH-dependent conversion of acetolactateto 2,3-dihydroxyketoisovalerate, catalyzed by acetolactate reductoisomerase(AHAIR); 3) conversion of 2,3-dihydroxyketoisovalerateto 2-ketoisovalerate catalyzed by dihydroxyaciddehydratase (DHAD); 4) NADPH-dependent formation ofvaline from 2-ketoisovalerate catalyzed by BCAA transaminase(BCAT) and several other transaminases .During synthesis, 2 mol of pyruvate and 2 mol of reducingequivalents in the form of reduced nicotinamide dinucleotidephosphate (NADPH) are consumed to produce 1 mol ofvaline. Pyruvate is formed from phosphoenolpyruvate (PEP)in glycolysis, which converts 1 mol of glucose to 2 mol ofpyruvate. The main source of NADPH in Corynebacteria isthe pentose-phosphate pathway (PPP) .2-Ketoisovalerate is also a precursor of leucine and pantothenate. In most microorganisms, includingC. glutamicum, the same four enzymes catalyze isoleucinebiosynthesis from pyruvate and 2-ketobutyrate. The latter isformed from threonine by threonine dehydratase (TD). Thus,the processes of biosynthesis of all three BCAAs are closely linked. The synthesizedBCAAs are removed from the cell by one export system,BrnFE .A schematic of valine biosynthesis and related metabolicpathways in C. glutamicum is shown in Fig. 1. The key enzymein the biosynthesis pathway of valine and other BCAAs isacetolactate synthase AHAS, which catalyzes the formationof either acetolactate from two pyruvate molecules or 2-aceto-2-hydroxybutyrate frompyruvate and 2-ketobutyrate (in isoleucine biosynthesis). Incontrast to E. coli, only one form of the AHAS enzyme wasfound in C. glutamicum , a tetramerconsisting of two catalytic and two regulatory subunits . The catalytic and regulatory subunits of AHASare encoded by the ilvB and ilvN genes, respectively. Togetherwith the ilvC gene encoding the acetolactate reductoisomeraseAHAIR, these two genes form the operon ilvBNC with twoadditional promoters within it. Expression from the three promotersleads to the formation of transcripts of different lengths. The ilvC gene is transcribed as part of all mRNAs;its expression efficiency is the highest among the three genes.The expression of the operon ilvBNC is thought to be controlledby the mechanism of transcription attenuation, whichis realized through the formation of secondary RNA structures(hairpins) on the transcript, i. e., transcription terminatorsthat arise in the regulatory region in the presence of high concentrations of BCAA . The regulatory regionis upstream of the ilvB gene; in addition to the sites responsiblefor hairpin formation, it also encodes a leader peptide(25 amino acids) enriched with isoleucine (2), valine (3), andleucine (2) residues. It is assumed that this peptide is a sensorelement of the regulatory system: when the concentration ofany of the BCAAs in the cells is low, its translation is sloweddown, resulting in no formation of terminator hairpin.When one or more BCAA were lacking, the expression ofoperon ilvBNC doubled; replacement of valine residues in theleader peptide with alanine residues led to loss of valine effecton expression . A significant increasein the expression of the operon ilvBNC in the presence of2-ketobutyrate was observed . The mechanism of thisregulation has not been investigated.AHAS activity is strictly inhibited by valine (Ki = 0.9 mM)as well as leucine (Ki = 6.0 mM) and isoleucine (Ki = 3.1 mM)by a feedback mechanism through amino acid attachment tothe regulatory subunit of the enzyme and is also competitively inhibited by 2-ketoisovalerate. Regardless of the number ofBCAAs present , the degree of inhibitionof AHAS activity does not exceed 57 % .It should be noted that AHAS has lower substrate specificitytowards pyruvate (Km = 8.3 mM) than towards 2-ketobutyrate (Km = 4.8 mM) , therefore, all other conditions being equal, the reactionof pyruvate condensation with 2-ketobutyrate leading toisoleucine synthesis is preferred.As for AHAIR (product of the ilvC gene), which catalyzesthe isomerization step and the conversion of acetolactate to2,3-dihydroxyketoisovalerate and 2-aceto-2-hydroxybutyrateto 2,3-dihydoxy-3-methylvalerate in the isoleucine synthesispathway, its activity depends on the presence of NADPH andis inhibited by the feedback mechanism of valine and leucine,but not isoleucine .There is little information about the regulation of the activityof the enzymes controlling the third and fourth, final,steps of valine synthesis in C. glutamicum, as well as aboutthe regulation of the genes encoding their structure. It is onlyknown that the activity of dihydroxyacid dehydratase DHAD(product of the ilvD gene) is weakly inhibited by valine andleucine and not inhibited by isoleucine ,and the activity of transaminase BCAT (product of the ilvEgene) depends on NADPH availability. The donor aminogroup in the transamination reaction is L-glutamate (hereafterreferred to as glutamate), which is converted to 2-ketoglutarat;NADPH is required for glutamate regeneration by glutamatedehydrogenase. It has been shown that the reaction catalyzedby glutamate dehydrogenase is the main reaction ofnitrogen assimilation under conditions of ammonia excess,which usually take place in amino acid production processes.It has also been shown that alanine/valintransaminase(a productof the avtA gene) is involved in valine biosynthesis.Alanine/valintransaminase uses L-alanine or \u03b1-aminobutyrate as an amino group donorinstead of glutamate .Analysis of the dynamics of changes in the concentrationsof the metabolites of valine biosynthesis using a kineticmodelin C. glutamicum strain ATCC 13032 \u0394panBC \u0394ilvApJC1ilvBNCD showed that the rate-limiting sites in this chainare 1) reactions catalyzed by the AHAS and BCAT enzymesand 2) transport of valine from cells by BrnFE .The information obtained so far on the biochemical, genetic,and regulatory aspects of valine biosynthesis in C. glutamicumsuggests that the barriers to increasing valine production inthis microorganism are:\u2013 negative regulation of AHAS activity by valine, leucine,isoleucine, and 2-ketoisovalerate (retroinhibition);\u2013 low substrate specificity of AHAS to pyruvate;\u2013 negative regulation of ilvBNC operon expression by BCAA;\u2013 consumption of pyruvate for synthesis of isoleucine, leucine,and pantothenate; and consumption of 2-ketoisovaleratefor synthesis of the latter two compounds;\u2013 expenditure of pyruvate and its precursor FEP, key metabolitesof glycolytic processes, in cell energy metabolismand carboxylic acid synthesis, as well as in alanine formation;\u2013 necessity of NADPH for the second and fourth reactionsof valine biosynthesis;\u2013 low efficiency of the BCAA BrnFE export system withrespect to valine.In the following, we will review the approaches to overcomethese obstacles used in the creation of valine-producingstrains based on C. glutamicum (information on the strains ispresented in the Table).Increase in AHAS activity. There are several approaches toincreasing AHAS activity when creating valine-producingstrains. The key one is modification of the ilvN gene, whicheliminates retroinhibition of the enzyme. A number of mutationsin the sequence of the ilvN gene have been found toweaken the effect of BCAA on AHAS activity. These mutationsinclude substitutions of three amino acids, Gly20Asp,Ile21Asp, and Ile22Phe, in the IlvN regulatory subunit. The Ile22Phe substitution showed thebest effect in this series, which was later used in other studies. Similar effects were demonstrated formutations leading to Ala42Val, Ala89Val, and Lys136Glu substitutionsin the small subunit. The double Ala42Val-Ala89Valmutation resulted in almost complete resistance of the enzymeto inhibition by all three BCAAs .Enhancement of AHAS substrate specificity with respectto pyruvate. This approach is related to the possibilityof modifications of the catalytic subunit IlvB of AHAS thatincrease the affinity of the enzyme for pyruvate. Reliable dataon suitable mutations are scarce. A mutation was found in theilvB gene that leads to a replacement of alanine for valine atposition 138 of the large AHAS subunit. This mutation hasmade possible a 2.5-fold increase in valine production . It is assumed that this substitution leads to achange in the substrate specificity of AHAS with respect topyruvate. The molecular mechanism of action of the mutationremains unclear.Other mutations in the ilvB gene of the catalytic subunit ofAHAS leading to an increase in the enzyme activity towardvaline production are also known . These other mutations have not yet found practicalapplication.The modified AHAS enzyme can be introduced into C. glutamicumcells in two ways: either the cells are transformedwith a plasmid carrying a mutant gene or appropriatechanges are made in chromosomal DNA . Such manipulations result in a 2\u20133-fold increase in valine production. The use of autonomousexpression plasmids also makes it possible to increase AHASactivity by introducing additional copies of the ilvBN genesor the entire ilvBNC operon into cells. The latter leads to anincrease in the activity of not only AHAS, but also AHAIR.Overcoming the negative effect of BCCA on the expressionof the ilvBNC operon. The most rational approach tosolve this problem is overexpression of the ilvBNC operonusing expression plasmids. At present, overexpression of theilvBNCDE genes, in various combinations, is performed usingconstructs with strong constitutive promoters. These include,for example, promoters of superoxide dismutase (Psod ) andelongation factor Tu (Ptuf ) genes and a synthetic constructbased on trp and lac operon promoters (Ptac) . Other efficient promoters have also beendescribed . Modifications of this type lead to an increase in valineproduction by about 60 % .Optimization of the activity of DHAD and BCAT, whichcatalyze the last steps of valine biosynthesis, is provided byoverexpression of the genes encoding these enzymes , which is usually achieved by geneamplification on plasmids (see Table). For valine production,it is especially important to increase BCAT activity becausethis enzyme catalyzes the rate-limiting step of biosynthesis.Enzymes of the valine biosynthesis pathway are involved inthe formation of other metabolites such as isoleucine, leucine,and pantothenate . Consequently, activation ofthese enzymes and increased expression of the genes encodingthem increase the yield of all the above compounds. This leadsto contamination of the target product as well as a decrease inthe availability of cofactors, intermediates, and the enzymesthemselves for valine production. As a result, it also leads toa lower yield. Minimizing the formation of byproducts whencreating strain-producers requires suppression of the relevantmetabolic pathways while preserving the strains\u2019 ability togrow on poor mediaMinimization of isoleucine formation. As noted above,the synthesis of isoleucine (2-amino-3-methylpentanoic acid)is catalyzed by the same enzymes that are involved in valinebiosynthesis and begins with the condensation of pyruvateand 2-ketobutyrate . The obvious way to minimizeisoleucine formation is to decrease the concentration of2-ketobutyrate in cells, the interaction of which with pyruvatedetermines the direction of further reactions. 2-ketobutyrateis formed from threonine by the threonine dehydratase TD,which is encoded by the ilvA gene . Thethreonine dehydratase is negatively allosterically regulatedby isoleucine and positively regulated by valine .The most common modification of this gene in the creationof valine-producing strains is its inactivation by deletion(\u0394ilvA). Most strains were obtained using this modification(see Table). It results in the appearance of the strains\u2019 ability toproduce valine or a significant increase in the existing production.In this case, isoleucine auxotrophy occurs, requiring theaddition of isoleucine to the cultivation medium, which complicatesthe production process and may increase the cost ofproduction. In a number of studies to create valine-producingstrains, instead of complete inactivation of the ilvA gene, adirected modification of its promoter was performed. This hasresulted in a decrease in gene expression, isoleucine bradytrophy,and, as a consequence, increased production of valine.Another target for modifications aimed at reducing isoleucinebiosynthesis is AHAS. A variant modification of theenzyme\u2019s catalytic subunit that increases its specificity towardpyruvate and redirects cellular resources toward valine production is described above.Minimization of leucine and pantothenate formation.2-ketoisovalerate is a precursor not only to valine but also toleucine and pantothenate . The synthesis of leucine(2-amino-4-methylpentanoic acid) from 2-ketoisovalerate iscontrolled by the leuA, leuB, and leuCD genes localized indifferent regions of the chromosome. It is known that leuB andleuCD are subject to the control of the LtbR transcriptional repressor,while leuA regulation seems to involve the mechanismof attenuation of transcription . A modificationto preserve 2-oxoisovalerate for valine biosynthesis atthe expense of decreased leucine biosynthesis was carried outby J. Hol\u00e1tko and colleagues (2009) by reducing the expressionof the leuA gene by replacing the native promoter witha weaker one. The result was a 50\u201370 % increase in valineproduction, which is comparable to the effect observed whenthe expression of the ilvA gene is weakened.The synthesis of pantothenate from 2-ketoisovalerate is controlled by the panBand panC genes, which form one operon , and the panD gene which is located separately in thegenome . It was noted that the carbon fluxgoing to valine biosynthesis is 10 times higher than the fluxgoing to pantothenate biosynthesis, even in the strain withenhanced expression of panBC .However, inactivation of the panB gene or the entire panBCoperon has a favorable effect on valine production, eventhough it leads to pantothenate auxotrophy in strains. Thisinactivationallows valine production to appear in wild-typestrains and to increase valine production in valine-producingstrains by more than 30 % or even 50 % .Increasing availability of pyruvate. Pyruvate, the centerpieceof carbon and energy metabolism in all organisms, isa precursor not only to BCAA and pantothenate, but also tomany other compounds, including components of the tricarboxylicacid cycle (TCA cycle) as well as lactate and alanine. Efficient production of valine requires maintaininga pool of pyruvate in the cells and, therefore, enhancingpyruvate formation reactions and/or reducing its \u201coff-target\u201dconsumption. Pyruvate, which synthesizes 2 mol of reducednicotinamide dinucleotide (NADH), is a product of glycolysis. However, glycolytic enzyme activityis generally not increased in the development of valineproducers, except for the microaerobic process (see below).The main approach is to reduce the outflow of pyruvate, andits precursor PEP, into other pathways.One of the main pathways of pyruvate outflow is the TCAcycle. This process becomes less active in the late stages ofgrowth, which could be used to create favorable conditionsfor valine production. Indeed, a decrease in the growth rateof C. glutamicum is accompanied by an increase in pyruvatelevels in cells and an increase in valine . In valine-producing strains that are auxotrophicfor isoleucine and pantothenate, growth of cultures can becontrolled by changing the amount of supplementation withthese substances. Growth restriction also leads to increasedproductivity .Involvement of pyruvate and PEP in the TCA cycle occursboth through conversion of both compounds to oxaloacetate(OA) and of pyruvate to acetyl-CoA directly or through acetateand acetyl-phosphate . As a rule, increasing theproduction of valine as well as pyruvate itself is attemptedthrough reducing the activity of the pyruvate dehydrogenasecomplex (PDHC), which catalyzes the oxidative decarboxylationof pyruvate to acetyl-CoA. In C. glutamicum, this complexconsists of three subunits, E1, E2, and E3, encoded by theaceE, aceF, and lpd genes, respectively . Inactivation of the aceE gene by deletion (\u0394aceE) is oneof the most frequent steps in creating a valine producer (seeTable). The resulting strains require the addition of acetate inminimal medium, but the level of valine production increasesmanifold. Metabolomic analysis showed that inactivation ofaceE in wild-type C. glutamicum leads to a 13-fold increasein the pyruvate pool in cells .A characteristic feature of C. glutamicum strains devoidof PDHC is the production of valine in the absence of cellgrowth. Increased glucose utilization rate was achieved byadding maltose instead of glucose, using ethanol instead ofacetate, or inactivating the transcriptional regulator SugR. SugR inC. glutamicum is responsible for acetate-mediated repressionof the ptsG, ptsI, and ptsH genes encoding the enzymes ofthe phosphotransferase system (PTS). PTS ensures the conjugatedprocesses of sugars transport into the cell and theirphosphorylation . However, becauseof PDHC deficiency, all strains still needed acetate or ethanol,which is then also converted to acetate as an additionalcarbon source.To overcome this need, the native aceE gene promoter wasreplaced with mutant variants from a previously establishedpromoter library based on the dapA gene promoter . This allowed to obtain a series of C. glutamicumstrains with gradually decreased PDHC activity as wellas gradually decreased growth rate on medium containingglucose as the only carbon source. Transformed with thepJC4-ilvBNCE plasmid, these strains produced valine and didnot require acetate as an additional carbon source . A growth-dependent promoter of the aldehydedehydrogenase gene from C. glutamicum CP (PCP_2836) hasbeen used for the same purposes. This has led to a threefolddecrease in aceE transcription levels compared to the nativepromoter, as well as has had positive effects on both cellgrowth and valine production .It is also possible to reduce pyruvate consumption in theTCA cycle by decreasing the activity of the cycle itself. Forexample, suppression of the gene of the transcription factorRamA responsible for the TCA cycle activation has beenshown to contribute to efficient pyruvate production .The conversion of pyruvate to acetate is catalyzed bypyruvate:quinoxidoreductase (product of the pqo gene), theinactivation of which (\u0394pqo) leads to increased valine production(see Table), but also to impaired growth characteristics of strains. The combination of this modification with inactivationof PEP carboxylase (product of the ppc gene), which catalyzesformation of OA from PEP, resulted in a slight increasein valine production, however, the yield increased by 14 %. It was noted that the valine-producingstrain with inactivated aceE and pqo genes grew better andproduced more valine on maltose-enriched medium .Another pathway for the outflow of pyruvate is the formationof OA from it under the action of pyruvate carboxylase(product of the pyc gene). Inactivation of pyc in the creationof a valine-producing strain leads to an increase in yield to0.86 mol of valine per 1 mol of glucose . When developing a leucine-producing strain, it wasfound that, in order to minimize pyruvate outflow, inactivationof pyruvate carboxylase is more beneficial than inactivationof PEP carboxylase .Two other pathways of pyruvate consumption in C. glutamicumcells are the processes of lactate and alanine biosynthesis. Lactate formation catalyzed by lactate dehydrogenase(a product of the ldhA gene) becomes important interms of valine production under oxygen deficiency conditions and will be discussed further.Minimization of alanine synthesis is required under allconditions because this process leads not only to untargetedconsumption of pyruvate but also to loss of NADPH in theamino group transfer reaction and to unwanted impurities inthe final product.Alanine formation in Corynebacteria is catalyzed by thetransaminases AlaT and AvtA, which use glutamate and valineas amino group donors, respectively . It was noted above that AvtAis one of the transaminases involved in valine biosynthesis,but its role, compared with BCAT, is minorThe question of the participation of these transaminases inalanine biosynthesis in C. glutamicum remains open due tothe inconsistency of existing data. On the one hand, inactivationof alaT and avtA in the valine-producing strain has beenshown to reduce alanine formation by about 80 and 20 %,respectively . A significantdecrease in alanine synthesis (to less than 0.2 g/L) is observedas a result of the inactivation of both genes .These data suggest that the AlaT aminotransferase is the majorone, but both enzymes are involved in alanine synthesis. Onthe other hand, in the proline producer, inactivation of alaThas no effect on alanine levels, whereas inactivation of avtAreduces this level by 48 % . Moreover,analysis of the transcriptome of the industrial valine producerline VWB-1 showed that its low level of L-alanine synthesis isnot associated with the alaT gene, the transcriptional level ofwhich in this strain is 5.1-fold higher than that in the wild-typestrain. It is assumed that a lower level of L-alanine synthesis isdue to the lower expression of the gene alr encoding alanineracemase that converts L-alanine to D-alanine . Thus, it is also impossible to give an unequivocalanswer to the question of whether inactivation of one or theother of these two transaminases is more advantageous interms of valine production.Increasing availability of NADPH. In C. glutamicum, themain supplier of NADPH is PPP, in which the reduction ofNADP+ to NADPH is provided by glucose-6-phosphate dehydrogenase(a heteromultimeric complex wherein one of thesubunits is encoded by the zwf gene) and 6-phosphogluconatedehydrogenase (a product of the gnd gene). The activity ofboth enzymes is negatively regulated by ATP, NADPH, andother metabolites . NADPH-dependentdecarboxylating malate dehydrogenase andisocitrate dehydrogenase play a minor role in the synthesisof NADPH from NADP+ . The source of NADP+ and, hence, the sourceof NADPH in C. glutamicum can also be NAD+, which isphosphorylated by NAD kinase (product of the ppnK gene)to form NADP+. This enzyme has been characterized as apolyphosphate-ATP-dependent NAD kinase that uses ATP tophosphorylate NAD+ .Theoretical analysis showed that the level of substrateconversion to valine (the yield) significantly depends on thereactions used for NADPH regeneration. The maximum yield,equal to 1 mol of valine per 1 mol of glucose, is obtainedwithout the expenditure of carbon for growth and synthesis ofNADPH. If NADPH is provided by isocitrate dehydrogenaseactivity, the yield is 0.5 mol of valine per 1 mol of glucose.Directing the entire carbon flux into the NADPH-generatingPPP results in a much higher yield of 0.86. In this analysis, themain target for the redirection of carbon flux from the TCAcycle to valine biosynthesis appeared to be PDHC. A scenarioin which carbon is not consumed for NADPH synthesis atall can be realized by the combined activity of pyruvate carboxylase(or PEP carboxylase), malate dehydrogenase, andmalic enzyme, theoretically capable of transferring hydrogenfrom NAD\u041d to NADP+ . Such a path-way, designated a transhydrogenase-like shunt, is involvedin NADPH formation for anaerobic isobutanol production inC. glutamicum . Thus, enhancementof PPP and NAD kinase activity are the most obviousways to increase the NADPH pool in the cell.From the point of view of the efficiency of the valine biosynthesisprocess, it is advantageous to combine the enhancementof PPP with some weakening of glycolysis. Indeed,inactivation of the glucose-6-phosphatisomerase gene pgi(this inactivation directs carbon flux from glycolysis to PFP)resulted in more efficient valine production in the C. glutamicumstrain \u0394aceE \u0394pqo \u0394pgi (pilvBNCE), producing48.0 g/L with a yield of 0.75 mol of valine per 1 mol ofglucose . Further analysis of thisstrain showed that inactivation of pgi results in increasedintracellular NADPH concentrations and decreased byproductformation . Monitoring cellular NADPHcontent using NADPH-dependent fluorescence also showedthat the C. glutamicum strain carrying \u0394pgi does accumulateNADPH .The growth deterioration observed in \u0394pgi-strains on mediumwith glucose has been attributed to a decrease in PTSactivity and suggested to be overcome by overexpression ofthe gene ptsG, which encodes a glucose-specific componentof this system . For pgi-mutants,enhancement of the alternative glucose transport system byinositol permeases IolT1, IolT2, and the glucokinase PpgK,which was used to produce lysine producer, is also effective.Another approach to increase the NADPH pool is relatedto the possibility of changing the specificity of glycolyticenzymes from NAD+ to NADP+. It has been implemented toimprove lysine production. Point mutations in the glyceraldehyde-3-phosphate dehydrogenase gapA gene that changedenzyme specificity resulted in a 35\u201360 % increase in lysineproduction .It was noted above that enzymes that synthesize NADPHare susceptible to negative regulation by various metabolites.Therefore, one approach to PPP activation is to introduceinto the corresponding genes mutations that increase enzymeactivity. Such an approach has been implemented for the zwfand gnd genes in works on methionine, proline, and riboflavinproducers. It has indeed led to an increase in the NADPHpool and production levels in cells .As for NAD-kinase, the studies published to date on enhancingits activity target isoleucine production. These studiesindicate that modifications that increase the enzyme activity lead to increased intracellular concentration of NADP+and NADPH and contribute to enhanced biosynthesis of thetarget product .Another attractive possibility for increasing NADPH availabilityfor valine biosynthesis is heterologous expression oftranshydrogenase genes, such as pntAB from E. coli, thatcatalyze NADP+ reduction involving NADH. This possibilitywas previously used to improve lysine production withC. glutamicum . A significant increasein intracellular NADPH concentration was observed whenpntAB expression was combined with overexpression of theppnK gene . Introduction of PntAB fromE. coli into the valine-producing strain C. glutamicum \u0394aceE\u0394pqo (pJC4ilvBNCE) resulted in a significant decrease incarbonflux in PPP and, consequently, an increase in yield to0.92. This is the highest yield , which isonly 8 % below the theoretical maximum of 1 mol of valineper 1 mol of glucose .Under oxygen deprivation, C. glutamicum cultures show verypoor growth capacity but metabolize sugars to organic acids. When byproductsynthesis is suppressed, producer strains adapted to such conditionsshow higher productivity than strains requiring aeration. Valine biosynthesis under normal conditions isan aerobic process because it is carried out by growing culturesactively generating NADPH. For efficient production ofvaline under oxygen deprivation, strains require a complexmodification involving both valine biosynthesis enzymes andglycolysis enzymes. Such a modification was performed byS. Hasegawa and colleagues .The C. glutamicum R strain with inactivated lactate dehydrogenase(\u0394ldhA) and overexpression of the ilvBNCE genesencoding the enzymes of valine biosynthesis was used as thebasis for creating strains producing valine under microaerobicconditions. This strain is incapable of producing valine underoxygen deficiency because it has an imbalance of cofactors:2 mol of NADPH are consumed while 2 mol of NADH aresynthesized to produce 1 mole of valine.The appearance of valine production was achieved byusing two approaches. The first approach was to change thespecificity of AHAIR from NADPH to NADH by site-directedmutagenesis of the ilvC gene (constructing the ilvC\u2122 gene).The second approach was to replace the NADPH-dependenttransaminase BCAT with NAD-dependent leucine dehydrogenase(LeuDH) from Lysinibacillus sphaericus . The additional introduction of the ilvN gene encodinga mutant AHAS regulatory subunit (ilvN GE) resistantto BCAA inhibition has allowed to produce a C. glutamicumstrain (pCRB-BN GEC\u2122)(pDLD)/\u0394LDH) that produced172.2 g/L of valine for 24 h under microaerobic conditionswith periodic fermentation, which was more than 20-foldhigher than baseline. The yield was 0.63 mol of valine permol of glucose .However, in addition to valine, the cells of this strain accumulatedsignificant amounts of alanine, acetate, and succinateas byproducts. To eliminate their formation and increase thevaline yield, additional modifications were introduced into thestrain . Succinate formation via PEPand OA was suppressed by inactivation of the ppc gene, butthis resulted in reduced valine synthesis and glucose uptake,as the intracellular NADH/NAD+ ratio increased markedly.To restore the ratio to a level favorable for valine production,three genes involved in acetate synthesis were inactivated and the expression of five genes encoding glycolysis enzymes was increased. Asa result, valine production increased 9-fold and glucose uptake,7.6- fold. Since valine biosynthesis became an NADHdependentprocess, increasing the activity of glycolytic enzymesturned out to be beneficial in terms of accumulatingboth pyruvate and reducing equivalents.Decrease in alanine formation was achieved by inactivationof the avtA gene. In addition, the ilvN GE and ilvC\u2122 genes,which were previously expressed on the plasmid, wereplaced in the chromosome. The valine productivity of the newstrain was 149.9 g/L in 24 h of cultivation. The yield reached0.88 mol of valine per mol of glucose, which was significantlyhigher than that obtained in the first step .It should be noted that in both works, valine synthesis undermicroaerobic conditions was studied using non-growing cellspreconcentrated by centrifugation by a factor of 2 to 3. In thiscase, the measured valine concentration reached very highvalues, but the productivity per cell was comparable with thatdemonstrated in other studiesReplacement of enzyme specificity from NADPH to NADHto adapt the amino acid production process to microaerobicconditions has also been done in the development of E. colibasedvaline producer and C. glutamicum-based leucine and L-ornithine producers . In all cases, this resulted in anincreased yield of the target product.Microorganisms have multiple transport systems that ensurethe uptake of desired environmental components by cellsand release of metabolites, the excess of which can be toxic. The activity of such systemsdepends on the concentration of the transported substances, soit has long been thought that producing strains\u2019 own regulatorymechanisms are sufficient for excreting the target productseffectively . Transport engineering is complicatedby the complexity of its quantification and the factthat specific transporters are not known for each biotechnologicallyrelevant substance. In recent years, however, therehave been a growing number of studies showing the effect ofdirectional changes in export and import of the target producton strain productivity . Valine transportersin Corynebacteria have been detected and characterized, andthus are promising targets for modifications in the creationof producing strains. Valine import. The uptake of valine, leucine, and isoleucinein Corynebacteria occurs through a secondary Na+-dependentsymport carried out by the only known importer,BrnQ . BrnQ exhibits the highestaffinity for isoleucine. For valine and leucine, the affinity is1.7 times lower .Data on the regulation of BrnQ and the corresponding genein corynebacteria are extremely scarce. It is known that BrnQis activated when the intracellular concentration of BCAAis increased and that inactivation of thebrnQ gene increases isoleucine export from C. glutamicumcells and its production . It has been notedthat a similar modification favors growth and productivity ofthe isoleucine-producing strain WM001 in the early stagesof fermentation . The importance of theimporter for valine production is confirmed by transcriptomeanalysis of the industrial producer VWB-1, which showedthat the transcription level of the brnQ gene in this strain islower than that of the wild-type strain .Valine export. The BrnFE transport system is responsiblefor BCAA export from C. glutamicum cells . Amino acids are exported through a secondary H+-dependentprocess controlled by membrane potential . The brnFE transport system is the only knownexporter of valine, leucine, and isoleucine in C. glutamicum.It also transports methionine and homoserine, a precursorof methionine, isoleucine, and threonine . The brnF and brnE genes encoding,respectively, the large and small subunits of the transportsystem, are organized into a single operon controlled by thetranscriptional regulator Lrp (leucine responsive protein). Homologuesof Lrp, first discovered and characterized in E. coli, are presentin the genomes of various prokaryotes and regulate genesinvolved in amino acid metabolism . InC. glutamicum, the lrp gene is located divergently upstream ofthe brnFE operon. By binding to BCAA or methionine, Lrpbecomes active and, in turn, activates the brnFE promoter . Theeffect of cellular amino acid concentration on Lrp activity decreasesin the series leucine > methionine > isoleucine > valine.A study of industrial leucine and valine producers confirmsthat a high level of amino acid production either correlates witha high level of operon brnFE expression or is associated with an increased lrpand brnFE gene copy number .Analysis of the effect of operon brnFE on valine productionshowed that its overexpression does not affect the growthof C. glutamicum cells and increases valine production byabout 2\u20133 times . Overexpression of brnFEhas a similar effect on the production of isoleucine, methionine,and homoserine . The maximum effect on isoleucine productionwas obtained when lrp and brnFE expression were simultaneouslyenhanced .However, it was found that, unlike brnFE, overexpressionof the lrp gene suppresses cell growth ,although it also significantly increases valine production. Thenegative effect was counterbalanced by the use of a weakenedmutant form of this lrp1 gene found in the VWB-1 strain.Overexpression of lrp1 in the wild-type C. glutamicum strainresulted in a 16-fold increase in valine production, from 1.9to 30.2 mmol/L per 96 h of cultivation. The combination of lrp1and brnFE overexpression enhanced the effect. Isoleucine productionwas not significantly affected by such manipulations,from which the authors concluded that isoleucine is a lesssuitable substrate for brnFE than valine .Simultaneous amplification of the expression of both genes,lrp and brnFE, combined with overexpression of the ilvBNCgenes and inactivation of aceE, alaT, and ilvA, resulted in a strain that produced 437 mM (51 g/L) valine when fermentedwith feeding .Thus, modifications of BCAA transport systems aimed atreducing the influx of amino acids into the cell and increasingtheir secretion from the cell have a positive effect on theproduction of the amino acids .In recent years, interest in the use of valine as a feed additivehas increased significantly. In the Russian Federation alone,the consumption of valine has increased almost 10-fold overthe past five years, reaching 5,000 tons per year. Modernindustrial production of valine is based on microbiologicalsynthesis using renewable plant raw materials and producingstrains with a modified genetic program. The efficiency ofamino acid production largely depends on the productivityof the producer strains, which are a key element of the entireprocess chain. Although significant progress has been madein the creation of producing strains (see Table), the creationof new strains with unique characteristics is still relevant.It is worth noting that the recently developed processeswith reduced aeration have a higher potential compared to thetraditional aerobic processes of valine production. However,it should be noted that such processes are biphasic: in the firstphase, biomass is produced aerobically, while in the secondphase, valine biosynthesis occurs under microaerobic conditions.Currently, the two-phase processes show low efficiency,and more research in this area is required.Nowadays, the main approach to creating valine-producingstrains, which has replaced random mutagenesis, is rationalmetabolic engineering aimed at enhancing the valine biosynthesisprocess and minimizing the formation of byproducts.In recent years, this approach has been actively enriched bythe application of systems engineering and synthetic biologymethods. The combined analysis of \u201comics\u201d data expandsour knowledge of the metabolic and regulatory processes ofC. glutamicum and allows us to develop new strategies forcreating producers of valine and other amino acids. The recentemergence of rapid genome editing systems that speed up theprocess of obtaining new strains should help to implementthese strategies.Further progress in the creation of producer strains willinvolve a shift from studying the properties of a cell populationto studying the properties of individual cells , aswell as extensive application of computer modeling and using new knowledge about gene expressionregulation .The approaches perfected in the creation and improvementof valine producers can be used to create producers of otherBCAA and pantothenate, the substances that also have a significantmarket potential.The authors declare no conflict of interest.Baritugo K.A., Kim H.T., David Y., Choi J.I., Hong S.H., Jeong K.J.,Choi J.H., Joo J.C., Park S.J. Metabolic engineering of Corynebacteriumglutamicum for fermentative production of chemicals in biorefinery.Appl. Microbiol. Biotechnol. 2018;102(9):3915-3937. 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DOI 10.1002/bab.1963.Zheng L., Zuo F., Zhao S., He P., Wei H., Xiang Q., Pang J., Peng J.Dietary supplementation of branched-chain amino acids increasesmuscle net amino acid fluxes through elevating their substrate availabilityand intramuscular catabolism in young pigs. Br. J. Nutr.2017;117(7):911-922. DOI 10.1017/S0007114517000757"} +{"text": "Ultra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog\u00ae and Lyumjev\u00ae formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model.We employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy.Through experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step.This study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future. \u2022Hexamer dissociation is not the absorption rate-limiting step for insulin lispro.\u2022Lyumjev excipients enhance insulin microvascular absorption and diffusion.\u2022Vascular endothelial transit determines the overall absorption for insulin lispro.\u2022Insulin diffusion studied for the first time at the injection site of live animals.\u2022In\u00a0vivo imaging is a powerful tool to study injection site dynamics. Most therapeutic insulins are available in stabilized hexamer forms, which after subcutaneous (SC) injection, dissociate into dimers and monomers for microvascular absorption, thus leading to a delay in time action . Rapid-a2 at a cellular level resolution . To. To16]. We confirmed the accuracy of quantification by observing linear proportionality between the injected doses , and measurement of total amounts of dye-labeled lispro in an expired mouse-ear A.Figure\u00a0We injected the dye-labeled lispro in both the Humalog and Lyumjev formulations ,22. The We report the values of k1 , at the k1 D. Notablce k1\u226bk2 , we can t1/2 of the dye-labeled lispro in the Lyumjev formulation at 32.8\u00a0min, which was almost half of that in the Humalog formulation at 56.9\u00a0min and deep (>1\u00a0mm) imaging techniques for different types of injectable drugs.Our pharmacokinetics data on pigs along with the kinetics and diffusion modeling of the experimental data from mice show that hexamer dissociation rate and diffusion are not the rate-limiting step for dye-labeled lispro absorption from either the Humalog or Lyumjev formulation. While we found that ectively . Modifyiectively . Literatectively ,22. Thouectively . To get ectively ,35,36. Pectively ,38. The ex\u00a0vivo ,39,40. OIn summary, we demonstrated the use of photoacoustic imaging to qualitatively and quantitatively study the injection site dynamics of rapid- and ultra-rapid insulin formulations. We addressed critical questions on the mechanisms of enhanced absorption of the Lyumjev formulation, including microvascular transport, drug diffusion, and tissue expansion. These experiments coupled with the kinetic model show that hexamerization of rapid-acting insulin analogs and subsequent hexameric dissociation rate for absorption is not the rate-limiting step for lispro, which has been a question of debate for more than 20 years. Overall, the application of OR-PAM demonstrates that the methodology can play a significant role in understanding the real-time behavior of a wide range of therapeutics at the injection site.The data that support the conclusions are present in the main draft or the supplementary information. The data processing and quantification procedures are described in detail in the Methods section.L.V.W., S.S.O., J.M.B., C.D.P., and A.K. conceived the project and the ideas. C.D.P. designed the chemistry for dye labeling and analyzed the chemistry data. F.A.V. labeled the insulin molecules with the sulfo-cyanine7.5 dye and characterized them. F.A.V. and A.K. prepared the insulin and dye buffer solutions. A.K. and K.M. designed and built the scanning photoacoustic microscope. J.S. and R.C. wrote the LabVIEW software for photoacoustic data acquisition. A.K. designed and performed all the photoacoustic experiments, wrote the MATLAB codes, and analyzed all the photoacoustic data. A.K., K.M., and L.V.W. designed the photoacoustic quantification algorithm. A.K. and K.M. devised the pharmacokinetics and diffusion methodologies. A.L.C. designed and supported the pharmacokinetics study in pigs and A.E.S. performed the pharmacokinetic experiments. R.M. prepared the unlabeled insulin lispro samples, and designed and performed the SV-AUC experiments. S.A.B. designed and performed the NMR spectroscopy analyses. A.K., C.D.P., K.M., J.M.B, and L.V.W. interpreted the final data. P.B.A., E.L., and R.L.B. were involved in active discussions. L.V.W., S.S.O., and J.M.B. supervised the project. A.K. wrote the manuscript. C.D.P., K.M., R.C., J.M.B, S.S.O., and L.V.W. contributed to writing the manuscript."} +{"text": "Y. Burenina, N. L. Lazarevich, I. F. Kustova, T. S. Zatsepin, M. P. Rubtsova, and Academician O. A. Dontsova, was originally published electronically in Springer-Link on August 29, 2022 without Open Access. After publication in volume 505, issue 1, pages 137\u2013140 the authors decided to make the article an Open Access publication. Therefore, the copyright of the article has been changed to \u00a9 The Author(s) 2022 and the article is forthwith distributed under the terms of a Creative Commons Attribution 4.0 International License ("} +{"text": "Proc. R. Soc. B289, 20220212. . (doi:10.1098/rspb.2022.0212)Block effect in models presented in tables t and z statistics and p-value for the treatment effects are also replacing those reported in the text of the paper.With this, the correct values of the respective"} +{"text": "Nature Communications 10.1038/s41467-019-13364-2, published online 29 November 2019.Correction to: Since the publication of this work, Brittany M. Curtiss has changed their name from Brittany M. Smith. This has now been amended."} +{"text": "The snowballing growth of scientif ic data obtained using modern techniques of genome editing (GE) calls for their critical evaluation and comparison against previously applied methods such as induced mutagenesis, which was a leading method of genome modif ication for many decades of the past century, and its application has resulted in a huge diversity of cultivars. However, this method was relatively long and included a number of stages from inducing multiple mutations using different mutagenic factors to crossing and selecting the most valuable cultivars for several generations. A new technology of genetic engineering and transgenesis enabled us to radically reduce the time required to obtain a new genetically-modif ied cultivar to one generation and make the modif ication process more effective and targeted. The main drawback of this approach was that an introduced transgene might uncontrollably affect the other genes of a recipient plant, which led to the limitations imposed on transgenesis application in many countries. These limitations have been effectively surmounted thanks to the development of GE techniques allowing for a precise modif ication within a single gene that in many characteristics make it similar to a natural allele , which has paved the way for wide application of GE in routine breeding. The paper reviews the main stages of GE development in its application in plants. It provides short descriptions of different GE techniques, including those using protein editors such as zinc-f inger and transcription activator-likeeffector nucleases (TALEN), and the CRISPR/Cas9 technology. It lists a number of achievements in using GE to producenew cultivars of higher yield that are resistant to unfavorable factors and have good nutritional properties. The reviewalso considers the de novo domestication approach, which allows for faster obtaining of new cultivars from naturalvarieties. In the conclusion, the future ways of GE development are discussed. Continuous accumulation of spontaneous mutations is thefoundation of evolution in living organisms. Mutation frequencydepends on the features of a creature\u2019s genetic apparatusand varies from 10\u20139 to 10\u201312 nucleotides/cell generations.Mutations commonly occur due to disrupted key biologicalprocesses such as DNA replication, reparation and recombination, and onlytheir insignificant part becomes involved in the evolutionaryprocess while others are eliminated during selection. Themutations induced by chemical agents, radiation and otherfactors are random but of high frequency that provokes a hugenumber of mutation events in a genome .However, selecting useful alleles and their combinations is along-term process that involves crossing with wild genotypesand cultivating necessary ones for several generations. Nevertheless,significant number of modern cultivars have resultedfrom the breeding programs using induced mutagenesis thatwere launched in the beginning and middle of the 20th century,in other words, they are partially a subproduct of nucleartechnology developmentThe second method for obtaining new versions of geneslies with genetic engineering and transgenesis. The mainadvantage of this approach, if compared to induced mutagenesis,is that is allows for fast and dedicated effect on a certaintrait through an induced alien transgene, which significantlyreduces the time required to obtain a genetically modifiedorganism (GMO) . However, along with theadvantages, the method has certain drawbacks that will bediscussed in a separate section belowThe further advancement of genome modification technologiesis related to improved dedicated delivery of vectormolecules so they could directly affect certain genetic loci,which has been implemented in the gene targeting strategy. The strategy allows one to overcome themain disadvantage of transgenesis that is a possibility for atransgene to introgress into different genomic regions, makesthe expected effect more targeted and prevents off-target editingof other genes. Its foundation was initially based on thephenomenon of homologous recombination between a vector\u2019sDNA sequence and a genomic DNA sequence homologousto it . The process resultsin either deletion of a gene or its part so the gene losesits functionality (gene knockout); or insertion of additionalsequence; or modification of certain base pairs (point mutation).Genetic targeting is widely used in human and animals.In particular, it is applied to study the genetic diseases in celllines for which a knockout or a modification of a potentiallypathogenic gene can be performed in vitro .Together with homologous recombination, the genomes ofeukaryotic organisms employ non-homologous end joining(NHEJ) that may generate unpredictable frequent mutationsduring DNA repair .Another big advancement that has significantly increasedthe efficacy of genetic targeting has become the developmentof artificial endonucleases such as meganucleases, zinc-finger(ZF), transcription activator-like effector (TALEN) and Cas9site-specific nucleases. It is the use of those nucleases thathas given birth to a new specific term \u201cgenome editing (GE)\u201dalthough today it refers to any methods of gene modification.ZF and TALEN nucleases are used in combination withtargeting proteins such as ZF domains and the proteins similarto TAL effectors, respectively. In case of Cas9 nucleases, it isCRISPR RNA that gave birth to the CRISPR/Cas9 technologythat has revolutionized GE being the least laborious, relativelyinexpensive and most precise and effective technology to thedate. For the time passed since its introduction in 2012, it hasbeen applied for editing of a huge number of living organismsfrom humans to yeast .In what follows, the results obtained in plants with differentgenome modification techniques will be considered.The effect radiation has on heredity was first demonstrated byRussian botanist Georgy Nadson and American genetic scientist Hermann J. Muller . Their discovery fostered multiple genetic studies thatwent in parallel with the development of wave and nuclearphysics. Among such studies were those carried out by prominentRussian scientists including A. Sapegin who studiedradiation-induced mutagenesis in common wheat , and N. Timofeev-Resovsky who started a new directionin radiation genetics . At the sametime, chemical mutagenesis was studied by N. Koltsov andhis disciple I. Rapoport whose achievements became crucialfor applying the method in plant selection .Since the 1930th, both radiation and chemical mutagenesistechniques have been used all over the world to produce morethan 3200 cultivars of 200 species (https://mvd.iaea.org).In this respect, Russia takes the fourth place (6.7 % of mutageniccultivars) after China, India and Japan . In our country, the mutant plants have been used toobtain the cultivars of winter/spring wheat, barley, soybeans,lupin, oat, beans, etc. For instance, common wheat cultivarNovosibirskaya 67 was created using the radiation techniqueand became the fruit of the joint efforts of the breeders ofNovosibirsk Experimental Station and Institute of Cytologyand Genetics of Siberian Branch of the USSR Academy ofSciences . For a long time, the cultivar hadremained the leading crop of Western Siberia in terms ofplanted areas for it combined high productivity, excellent bakingproperties and was resistant to a number of diseases. Thescientists of Research Institute of Oil Crops (Krasnodar) usedchemical mutagenesis to produce Pervenets, a new sunflowercultivar whose oil quality was comparable to that of olive trees. The dwarfism mutation was used by N. Borlaug to breedthe cultivars of non-lodging high-yielding common wheatthat paved the way for the so-called green revolution in themiddle of the last century . E. Sears and F. Elliotused experimental mutagenesis in combination with long-termhybridization to transfer the loci of resistance to rust and smutfrom the wild varieties of goat and wheat grass to commonwheat . G. Stubbe (DRG) applied 5-timeX-ray irradiation and selection in several generations of smallfruitedwild tomato to increase its fruit to the size commonlyobserved in cultivated tomato .The next technology to obtain new gene versions that cameonto stage was genetic engineering or artificial transgenesis.In its essence the technology is introduction of an alien gene(transgene) into a living organism that facilitates the last toobtain predictable and inheritable traits. In plants, transgenesare delivered using the specialized vectors created using thetumor-inducing (Ti) plasmids of agrobacteria . Since all plant species have similar genetic code, itmeans a transgenic organism is able to express alien genes.This approach had multiple advantages if compared toinduced mutagenesis. First, it significantly widened the possibilityfor dedicated modification of living organisms becausetransgenes could have the traits untypical for a recipient, sothey could not be obtained using mutagens .Second, the technology significantly reduced the scale andduration of selection especially after such markers as antibioticresistance and reporter genes were introduced into vector DNAand allowed for fast and effective identification of geneticallymodified organisms (GMO). In terms of fundamental science,transgenic organisms became a convenient model for studyingthe functions of a particular gene and their phenotypicalmanifestationsGenetic engineering has been used to obtain multiple geneticallymodified cultivars of corn, rice, soybean, cotton, rape,potato and others whose farming areas take hundreds of millionsof hectares all over the world . One of the examples of transgenic plants isGolden Rice that has high content of \u03b2-carotene, a precursorto vitamin A whose deficiency leads to xerophthalmia, a widespreadeye condition in South-East Asia. To obtain this cultivar,a gene of phytoene synthase (Narcissus) was introducedinto a local variety using the bioballistics technique . Another example of successful transgenesis inagriculture is transgenic soybean.Its cultivars are widely represented on the market and areknown for their resistance to different herbicides such asRoundup (glyphosate), glufosinate, Dicamba. Others containthe gene of Bacillus thuringiensis (BT), whose toxin makethem resistant to insects .An analogous transgene was introduced to cotton andmade it resistant to the cotton budworm, a common pest forthis species . Genetic engineering has alsoproduced the transgenic varieties of cotton, maize and raperesistant to herbicides ,and that of maize resistant to insects andmany others.All these examples prove the technology has been successfullyapplied in the agricultural sector of such countries asthe USA, China, India, Argentina, Canada and others whereindustrial agriculture and transgenic plants were permitted unlikethe majority of countries where the using and growing ofGMOs was prohibited or unlike Russia that only allowed forimport of GMOs as food products, forage, and research objects. Although, most of GMO-related concernshave been due to prejudices or the rivalry of agrochemicalcompanies, it is still cannot be stated that all such concernshave been completely ungrounded. GMOs present a certaindanger for ecosystems, e. g., if we have produced herbicideresistantplants, how can we be certain that these genes willnot be transferred to weeds by pollen while cross hybridization.There is also a risk that a transgenic plant can affect nontargetorganisms such as plants possessing BT-toxin genescan kill non-hazardous insects . Thelong-term consequences of transgenesis remain unclear sincea transgene can enter different regions of a genome and ruinother genes\u2019 expression. As for their direct harm to humanhealth, multiple scientific research has shown that GMOsand their products are of no more harm than traditional crops.The basis of GE is dedicated changing of a limited gene regionthat may be achieved in different ways. Considering the earlydays, the first experiments were applying oligonucleotidesfor DNA editing, e. g., two genes (defective green fluorescentprotein and acetolactate synthase) of tobacco and corn wereedited using chimeric RNA/DNA oligonucleotides in 1999. In the last case, theediting resulted in a low-frequent resistance to imidazolineand sulfonylurea. This study was followed by analogous worksto alter these and other species of plants ,but the effectiveness of the techniques remained comparableto that of spontaneous mutagenesis .Single-stranded DNA oligonucleotides proved to be of abit higher efficacy , but it still was not highenough. Moreover, selecting edited plants became a problem that could not be resolved without using vectors. For thatreason, the perspectives of this direction remain questionableAnother direction of GE is related to using endonucleases,special enzymes provoking double-stranded ruptures in a DNAmolecule. Repairing the ruptures may occur either throughrecombination with a homologous DNA fragment that hasbeen placed into a vector and transformed into a cell nucleus.The first endonucleases used for this purpose were homing endonucleasesrecognizing DNA regions of 12\u201345 nucleotides.The specificity of these regions varied and depended on a typeof nuclease, e. g., using the I-CeuI homing endonuclease andthe 35S promoter, the bar gene was precisely inserted into asite of a corn genome to make the plant resistant to phosphinothricin.Analogous site-specific insertion was carried out in a cottongenome (genus Gossypium) to provide the last with genes hppdand epsps making the plant resistant to glyphosate . The I-SceI homing endonuclease was used toreplace a region in a barley genome to a homologous onedelivered in a vector with a functional gene of resistance tohygromycin .In the GE techniques based on protein editing, one useschimeric nucleases. These are complex proteins containingtwo structural components, one of which binds specificallywith certain nucleotide sequencies of genome DNA, directingat them the second component, a nuclease catalyzing DNAsplitting. These proteins are delivered into a plant\u2019s genomeusing expression vectorsThe first such vectors were ZF nucleases that typicallycontained three \u201czinc fingers\u201d as a directing structure. Thefingers are protein domains binded with one or two ions ofzinc and capable of recognizing and specifically binding witha certain nucleotide triplet in DNA sequence. In some case,the number of these domains were increased to 6, so their spe-cificitylevel raised to 18 DNA nucleotides .For the first time, ZF nucleases were applied for genomeediting in plants in 2005 when a corresponding vector wasinserted in Arabidopsis so indels of different length, mostlydeletions (78 %), were found . Since then,a lot of analogous projects have been performed in tabaco,soybean, corn, tomato, apple and fig trees . However, the technique has turned outto be quite laborious and expensive for it requires a uniqueprotein structure of ZF nuclease to be created for each individualsequence of target DNA. Additionally, the technique isnot precise in recognizing nucleotide triplets, which results ina large number of DNA splits in off-target regions. For thesereasons, the technique is quite rarely applied these days.TALEN chimeric nucleases have proved to be more effective.The protein domains serving as their directing structuresare the prototypes of the natural TAL effectors of certainbacteria, and each of them recognizes only one nucleotide. Inthis case, the DNA recognition mechanism is more unambiguousthan that of ZF nucleases and allows for relatively easycreation of a structure that specifically recognizes a requiredDNA sequence. The last is binded with an enzyme splittingthe DNA and enables for atheoretically very precise double-stranded rupture within anygenome region.In 2011, the technique was recognized as the most perspectiveGE approach. By 2017, it had been used to edit12 plant genomes including those of such domestic plantsas rice, wheat, corn, tobacco, barley, potato, sugar cane, soybean,tomato, and of model plants such as Arabidopsis andBrachypodium. In total, in these plants, more than 50 geneshave been edited (mostly knocked out) ,e. g., to increase bioethanol output in the sugar cane, TALENnucleases were used to knock out its genes responsible forhigh lignin content . To exclude potatosweetening while storing in cold, vacuolar invertase catalyzingthe sucrose splitting into fructose and glucose was knockedout . Using the TALEN and CRISPR/ Cas9approaches it became possible to knock out the alleles ofpowdery mildew resistant loci in every three subgenomes ofallohexaploid common wheat Triticum aestivum L. . To improve the quality ofsoybean oil, the genes of desaturase enzymes were mutated.To facilitate the TALEN technique, a number of softwaresolutions have been developed to search for edited sites, createvector structures and detect off-target sites such as TALENdesigner.Unlike the chimeric nucleases, in the CRISPR/Cas9 technology,DNA-recognizing structures are not proteins but shortRNAs that, first, are far more precise due to their complementarityand, second, are much easier and chipper to synthesize.The theoretical foundation of the technology was laidwhile studying the mechanism bacteria use to get protectedfrom pathogenic viruses (bacteriophages) . There have been published many reviews devoted toCRISPR/Cas9 . In plants, the technology wasfirst applied in 2013 The simplified vector included the genes of the Cas9 protein,a guide RNA (gRNA) analogous to bacterial CRISPRRNA and an additional sequence coding a nuclear localizationsignal (NLS). The vector was introduced in plant cellsusing either agrobacterial transformation or bioballistics. Asa result, cellular DNA were transcripted by the intercellularRNA polymerase III. From the RNA template encodingCas9, a protein is translated on ribosomes, which then entersthe nucleus via NLS. In the nucleus the gRNA and Cas9 gotunited to bind with its target site following the principle ofcomplimentary interaction.An important element that, in many ways, determined thespecificity of the binding was a protospacer adjacent motif(PAM), a nucleotide triplet (commonly NGG) placed nearthe 3\u2032-end of the target site. The catalytic domains of thenuclease provoked single-stranded breaks near the PAM toactivate a repair mechanism that could act in two ways: nonhomological end joining (NHEJ) being prone to the errorsproducing the indels of one or several nucleotides that shiftthe reading frame of the coded protein and disrupting itsfunctionality to the degree of a knockout. The second way ishomology-dependent repair (HDR) that edits the target siteor introduces a new sequence that can be undesirable for anexperiment, but the last is only possible if such a fragment ofdonor DNA has already presented in the region being editedThe key element leading to successful genome edition viaCRISPR/Cas9 has been selecting a gRNA for a target gene.The site of interaction with gRNA does not usually exceed30 bp. The presence of PAM at the 3\u2032-end of this region is animportant condition for selecting a site to be edited. Anotherimportant criterion for gRNA selection is the number andlocalization of the sites for off-target editing, whose search ina genome is performed individually for each particular gRNAusing special software solutions like those available on http://crispr.mit.edu/.Lately, the GE technique using ribonucleoprotein (RNP)complexes has been actively developed. In this case, thetransforming agent is not a vector (plasmid RNA) but a readyto-use complex including Cas9 and a gRNA. This approachhas proved its efficacy when editing the genomes of corn,wheat and potato via bombarding the embryonal cells withgold microparticles .It is noteworthy that this alternative to using an agrobacterium,which by itself can cause an undesirable genetic effect,allows CRISPR/Cas9 to go beyond the GMO approach andovercome the forbiddance against its application in the agriculturalindustry. Its other advantage is the reduced likelihoodof DNA cutting in off-target sites because the lifetime of adelivered RNP complex is much shorter than its DNA expression.At the same time, employing bioballistics for deliveringRNP complexes has a number of drawbacks related to the technique\u2019sexcessive traumaticity for plant tissues, complexity oftransformation and regeneration, and low editing frequency.For that reason, vector-based agrobacterial transformation stillremains a leading approach to CRISPR/Cas9.Genome editing is a technology that can serve both applied \u2013obtaining plants with new useful properties \u2013 and fundamental\u2013 studying the functions of genes \u2013 purposes. The fundamentaltasks are solved using the methods of inverted geneticswhen scientists manipulate genetic sequencies knocking outthis or that gene to see what consequences it will cause in thephenotype.As for applied problems they are quite diverse and in whatfollows, the main directions of CRISPR/Cas9 application forbreeding will be considered.Resistance to pathogensThe Table displays the studies aimed at creating the plantsresistant to different pathogens. For instance, in rice (Oryzasativa L.) applying CRISPR/Cas9 resulted in its resistance tothree pathogens: bacterial blight, tungro spherical virus andblast fungus. In the first case, the resistance was achieved afterknocking out one of the S genes responsible for sensitivityto bacterial blight .In the second case, the host\u2019s eIF4G gene was knocked outwhose product controlled the initiation of viral RNA translation. And finally, in case of fungalpathogen, it was the OsERF922 gene that was knocked outand it led to the reduction in ethylene hormone level in thecells and increased resistance .In T. aestivum, fungal pathogen Blumeria graminis f. sp.tritici causes the so-called powdery mildew that significantlyreduces the yield of common wheat in many regions.Currently, the S genes responsible for the sensitivity to thefungus have been edited. In one of such studies, the MLOgenes were knocked out , in another \u2013 theEDR1 (enhanced disease resistance) genes . It has been shown that in both cases, a knockout ofall three homoelogical copies of the gene is to be achievedsince knocking out only one or two copies has only resultedin partial resistance to the disease.In Solanum lycopersicum L., application of CRISPR/Cas9has made it possible to obtain tomato cultivars resistant tobacterial speck, yellow leaf curl virus and powdery mildew.In the first case, to enhance the barrier preventing bacterialinfiltration in the cells, the SlJAZ2 gene to control stoma closurewas mutated to foster the gain of function . In the case of viral disease, these were the pathogen\u2019sgenes that were targeted, namely, the viral envelope (CP)and replicase (Rep) genes. As a part of T-DNA, their shortsequencies were built in the plant\u2019s nuclear genome to enabletheir constitutive expression as RNA molecules, which incombination with Cas9 could effectively interfere the viralDNA .Resistance to abiotic stressA number of studies aimed at developing the cultivars resistantto abiotic stresses are listed in the Table. For instance, applyingthe protoplast technique in wheat led to mutating two genesrelated to drought stress (TaDREB2 and TaERF3) . A similar study was performed in soybean (Glycinemax L.) in which two genes related to the plant\u2019s resistanceto drought and salinity .In this field, not only applied but also fundamental researchhas been performed. Hence, it was found out that mitogenicactivatedprotein kinase (MAPK) reacted to drought by protectinga cell membrane from oxidation and regulating thetranscription of other genes. The role of one of MAPK geneswas determined using CRISPR/Cas9 for creating the knockoutmutants of this gene . In a similar way, theeffect of three genes on rice resistance to abiotic factors wasdetermined. It turned out, the genes coded MAPK (OsMPK2),phytoene desaturase (OsPDS) and betaine aldehyde dehydrogenase(OsBADH2) .YieldThe studies applying CRISPR/Cas9 to increase a plant\u2019s yieldare listed in the Table. The kernel size and thousand-kernel weight in common wheat were increased by provoking nonsensemutations in the homeological copy of the GW2 genebeing a negative regulator of these traits. The degree of theincrease was determined by a portion of mutated homoeologicalgenes . Later, the same authors couldchange the size and weight of a wheat kernel by mutating thesequence of another gene to belong to the same group: GW7in subgenomes B and D .The number of kernels in an ear was increased by editingfour target genes: CKX2-1, GLW7, GW2 and GW8 . In this case, the line homozygotic to the largedeletion in the CKX2-1 gene demonstrated the maximumincrease of the ear kernel number as well as maximum eardensity, which has confirmed the gene is a negative regulatoraffecting the number of kernels in an ear.A whole set of genes was knocked out in rice. These werenegative regulators of controlling such traits as tiller number(OsAAP3), ear size (OsDEP1), kernel weight (OsGW5) andsize and the number of kernels in an ear(OsGn1a) . Additionally, the rice model has beenapplied to integrate whole-genome sequencing, genealogyanalysis and CRISPR/Cas9 for full-scale identification ofthe target genes that affect quantitative traits including yield.At the first stage, the genealogy analysis detected multiplequantitative trait loci (QTL) associated with yield to carry outtheir association mapping. Comparison of the obtained mapagainst the rice\u2019s whole-genome sequence enabled for selectingcandidate genes to be knocked out using CRISPR/ Cas9for estimating their phenotypical effect. As a result, a wholeset of the genes crucial for yield was found.A study to preserve the yield in presence of stress factorsby mutating the ARGOS8 gene was carried out in corn(Zea mays L.) by J. Shi et al. (2017). The authors appliedCRISPR/ Cas9 to replace this negative regulator of ethyleneresponse by a promotor of another gene to increase ARGOS8expression. Field studied have demonstrated that the CRISPReditedplants had higher yield in drought condition than theirparents.Nutritional valueHigh amounts of phytic acid present in the grains of cereal,legume and oil crops. This acid is antinutrient and cannot bedigested by animals with single-chamber stomach and cancause environmental pollution. To reduce the acid\u2019s contentin corn, CRISPR/Cas9 was applied to knock out the gene ofthe enzyme catalyzing the stages of phytic-acid biosynthesis,so its production was blocked in the mutant line . The same corn was used to obtain cultivars with higherlevel of essential amino acids \u2013 lysin and tryptophane \u2013 byknocking out the genes having a negative effect on their biosynthesis.Changing gluten content and composition in wheat has beenanother topical issue due to the high spread of gluten intolerancein people. The results of two studies using CRISPR/Cas9and aimed at reducing in wheat the content of \u03b1- and \u03b3-gliadinscausing pathological reactions have recently been published.One group obtained the mutant lines with significantly reduced\u03b1-gliadin content . The other groupcreated lines with low \u03b1- and \u03b3-gliadins .The obtained wheat lines may become a start for new elitewheat cultivars to produce low-gluten products.In rice, application of CRISPR/Cas9 has led to the plant\u2019simproved nutritive and culinary qualities. It was achieved bymutating the Waxy gene to change the amylose/amylopectinratio in starch in the favor of amylopectin . This component determines the waxlike (sticky) qualitiesof starch in rice grains, which is very important for makingsushi. In another study, the opposite result was obtained, sothe gene responsible for suppressing amylose synthesis wasknocked out .In potato (Solanum tuberosum L.), the gene encodinggranule-bound starch synthase (GBSS) was knocked out, sothe obtained lines demonstrated a reduced level of amylose.To improve the quality of soybean oil, CRISPR/Cpf1 wasused to knock out genes FAD2-1B and FAD2-1A and producehigh-yield soy plants with high content of oleic acid .In sorgo (Sorghum bicolor L.), GE techniques were appliedto knock out the genes responsible for improper digestibilityand essential amino acids suppression .Using CRISPR/Cas9 the cultivars of rape (Brassica napusL.) were obtained with high content of oleic acid as well tomato cultivars with increased storability and increased content of lycopene, a vitaminA precursor of powerful antioxidation effect . These and many other studies are listed in the Table.De novo domesticationThe essence of the de novo domestication approach is speedingup a domestication process for a wild relative of an agriculturalplant. The wild relatives are widely used in selectionas donors of the genes responsible for a plant\u2019s resistance tobiotic and abiotic stresses. However, a simple crossing witha wild species only produces \u2018half-cultivars\u2019 that often losethe features of a cultural plant as well as the many qualitiesuseful for humansStudies into the genes of wild and domestic plants havefound the so-called \u2018domestication genes\u2019, in other words,mutations that transform a wild plant into one applicable forfarming.The idea behind de novo domestication is dedicated introductionof necessary genes into the domestication genes ofa cultural plant\u2019s wild relative. Such boosted domesticationmade the headlines in 2018, when CRISPR/Cas9 was appliedto convert a wild tomato into an almost cultural plant in a singegeneration. To do so, a list of genes to be modified to obtainthe plant\u2019s de novo version had been composed .Comparing the genetic sequences in both wild and culturaltomato enabled one to determine the structural modificationsto be implemented in the wild plant. At the final stage ofthe experiment, multiplex editing of four genes ,heading time and fruit size .Another example of such research is changing the morphologyof a barley ear. The naked kernel, unlike the rough one,has always been a sign of the crop\u2019s domestication. Nakedbarley is a traditional food and currently considered as adietary component of functional nutrition. In nature, thistransition from chuffy to naked kernel was determined bythe NUD gene losing its function due to deletion of 17 kb ina corresponding locus. Using CRISPR/Cas9, a naked-barleycultivar has been produced experimentally by knocking outNUD in a wild rough variety .Thus, de novo domestication opens huge perspectives forselective breeding, enabling one to obtain the results of hundredsand thousands of years of evolution in one generationIntensely developing GE technologies will soon see liftingmany of the limitations for their wide practical application.The development goes in the direction of higher modificationspecificity and off-target effects elimination by using new-typenucleases such as the Cas9 orthologs interacting with differentPAMs or completely new nucleases suchas Cas12a .Moreover, there are approaches that go beyond gene knockoutsand include other modifications as changing a nucleotideor a whole sequence. This method has proved effective whenediting a single DNA base to perform cytosine/thymine oradenine/guanine replacement. Such changes have becomepossible thanks to using specific enzymes being a combinationof cytosine deaminase, adenosine desaminase and nickase.Another technique that is developing fast is homologicalrecombination when an expressing vector is delivered in acell together with a donor DNA flankered by the sequencieshomologous to the site where endogenous DNA is replacedby a donor\u2019s one .In addition, transformation techniques are developing sincethe classical methods such as agrobacterial transformationand particle bombardment in many ways produce low outputof transformants. 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Science. 2008;321(5896):1676-1678.DOI 10.1126/science.1160550Zetsche B., Gootenberg J.S., Abudayyeh O.O., Slaymaker I.M., MakarovaK.S., Essletzbichler P., Volz S.E., Joung J., Oost J., Regev A.,Koonin E.V., Zhang F. Cpf1 is a single RNA-guided endonucleaseof a class 2 CRISPR-Cas system. Cell. 2015;163(3):759-771. DOI10.1016/j.cell.2015.09.038.Zhang A., Liu Y., Wang F., Li T., Chen Z., Kong D., Bi J., Zhang F.,Luo X., Wang J., Tang J., Yu X., Liu G., Luo L. Enhanced ricesalinitytolerance via CRISPR/Cas9-targeted mutagenesis of theOsRR22 gene. Mol. Breed. 2019;39:47. DOI 10.1007/s11032-019-0954-y.Zhang J., Zhang H., Botella J.R., Zhu J.-K. Generation of new glutinousrice by CRISPR/Cas9-targeted mutagenesis of the Waxy genein elite rice varieties. J. Integr. Plant Biol. 2018;60(5):369-375. DOI10.1111/jipb.12620.Zhang P., Du H., Wang J., Pu Y., Yang C., Yan R., Yang H., Cheng H.,Yu D. Multiplex CRISPR/Cas9-mediated metabolic engineering increasessoya bean isoflavone content and resistance to soya bean mosaicvirus. Plant Biotechnol. J. 2019;18(6):1384-1395. DOI 10.1111/pbi.13302Zhang Y., Bai Y., Wu G., Zou S., Chen Y., Gao C., Tang D. Simultaneousmodification of three homoeologs of TaEDR1 by genome editingenhances powdery mildew resistance in wheat. Plant J. 2017;91(4):714-724. DOI 10.1111/tpj.13599Zhang Z., Ge X., Luo X., Wang P., Fan Q., Hu G., Xiao J., Li F., Wu J.Simultaneous editing of two copies of Gh14-3-3d confers enhancedtransgene-clean plant defense against Verticillium dahliae in allotetraploidupland cotton. Front. Plant Sci. 2018;9:842. DOI 10.3389/fpls.2018.00842.Zhang Z., Hua L., Gupta A., Tricoli D., Edwards K.J., Yang B., Li W.Development of an Agrobacterium-delivered CRISPR/Cas9 systemfor wheat genome editing. Plant Biotechnol. J. 2019;17(8):1623-1635. DOI 10.1111/pbi.13088.Zhou J., Peng Z., Long J., Sosso D., Liu B., Eom J.S., Huang S., Liu S.,Cruz C.V., Frommer W.B., White F.F., Yang B. Gene targeting bythe TAL effector PthXo2 reveals cryptic resistance gene for bacterialblight of rice. Plant J. 2015;82:632-643Zhu T., Mettenburg K., Peterson D.J., Tagliani L., Baszczynski C.L.Engineering herbicide-resistant maize using chimeric RNA/DNAoligonucleotides. Nat. Biotechnol. 2000;18:555-558. DOI 10.1038/75435.Zhu T., Peterson D.J., Tagliani L., Clair G.S., Baszczynski C.L., BowenB. Targeted manipulation of maize genes in vivo using chimericRNA/DNA oligonucleotides. Proc. Natl. Acad. Sci. USA. 1999;96(15):8768-8773. DOI 10.1073/pnas.96.15.87.Zlobin N.E., Ternovoy V.V., Grebenkina N.A., Taranov V.V. Makingcomplex things simpler: modern tools to edit the plant genome.Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Geneticsand Breeding. 2017;21(1):104-111. DOI 10.18699/VJ17.228.:438-440.DOI 10.1038/nbt.3811.Zs\u00f6g\u00f6n A., Cermak T., Voytas D., Peres L.E. Genome editing as a toolto achieve the crop ideotype and de novo domestication of wildrelatives: Case study in tomato. Plant Sci. 2017;256:120-130. DOI10.1016/j.plantsci.2016.12.012"} +{"text": "Aristolochia hainanensis Merr. 1922, a well-known Chinese medicinal plant, is distributed in Hainan Province and Guangxi Province, China. In the current study, we sequenced the complete chloroplast genome of A. hainanensis. The complete plastome genome was 159,764\u2009bp in length, with a GC content of 38.8%, showing a typical quadripartite organization. The genome contained a large single-copy (LSC) of 89,134\u2009bp, a small single-copy (SSC) of 19,306\u2009bp, and a pair of inverted repeats (IRs) of 25,662\u2009bp. A total of 113 genes were annotated, including 79 protein-coding genes, 30 tRNAs, and four rRNAs. The trnK-UUU gene contained the longest intron (2644\u2009bp). The topology of the maximum-likelihood tree supported a close relationship between A. hainanensis and A. kwangsiensis. Aristolochia, which includes 450 species status on the IUCN Red List (https://www.iucnredlist.org/).The Aristolochiaceae are composed of approximately 550 species, most of which belong to a large group in the genus Aristolochia have been reported, including A. kaempferi, A. kunmingensis, A. macrophylla, A. mollissima, A. moupinensis, A. tagala, and A. tubiflora under the voucher number Rong-Jing Zhang 32021. Fresh leaves were sampled for total genomic DNA extraction using a modified CTAB method to obtain the final annotated data. The complete plastome genome was submitted to GenBank under the accession No. OL943803.We collected several individuals from Mt. Wuzhishan, Hainan, China . A specimen was deposited at SCAUB of 89,134\u2009bp and a small single-copy (SSC) of 19,306\u2009bp separated by a pair of inverted repeats (IRs) of 25,662\u2009bp. In total, 113 genes were annotated, including 79 protein-coding genes, four rRNAs, and 30 tRNAs. Among these genes, 15 contained one intron and three contained two introns. The Aristolochia and six species of the subgenus Siphisia. Three species of the genus Piper were used as outgroups. The sequences used for alignment are available in the GenBank database, including A. hainanensis (OL943803.1), A. kwangsiensis (MN965793.1), A. moupinensis (NC_041454.1), A. mollissima (NC_041457.1), A. kaempferi (NC_041452.1), A. manshuriensis (MN132862.1), A. delavayi (MW413320.1), A. tubiflora (NC_041456.1), A. contorta (NC_036152.1), A. debilis (NC_036153.1), A. tagala (NC_041455.1), as well as Piper kadsura (NC_027941.1), P. laetispicum (MH678665.1), and P. auritum (NC_034697.1). Sequences were aligned using the MAFFT alignment tool on Geneious Prime v.2021.2.2 . The best model was generated using jModelTest2 on XSEDE with 1,000 bootstrap replicates .The authors have complied with the International Union for Conservation of Nature (IUCN) policies research involving species at risk of extinction, the Convention on Biological Diversity and the Convention on the Trade in Endangered Species of Wild Fauna and Flora. Our study has been approved by local authorities . Lei Liu is the Deputy Director (e-mail: Conceived and designed the experiments: RJZ, WG, and MXL. Performed the experiments: MXL, MXF, and HZ. Analyzed the data: MXL. Wrote the paper: MXL. Revised the paper: RJZ, WG, MXL, and MXF. Supervised the project and approved the final version to be published: RJZ and WG. All authors agree to be accountable for all aspects of the work."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-022-21175-7, published online 09 November 2022Correction to: Kim Francis Andersen was inadvertently omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cL.M.R. and A.K. conceived the study and design. L.M. included the patients and drafted the manuscript; T.B. performed the experiments; M.F., K.F.A., A.L., J.F. and A.K. supported the data analysis and critically revised the manuscript. All authors read and approved the final manuscript.\u201dThe original Article has been corrected."} +{"text": "Muscle\u2010liver\u2010brain\u2010eye Nanism\u00a0=\u00a0dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2\u2010year\u2010old boy with WT and MUL and present a review of literature on WT in MUL.Mulibrey\u2010Nanism of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15\u2009years post treatment for WT and other is our patient. AFatrial flutterASDatrial septal defectMULMulibrey NanismWTWilms tumor1Muscle\u2010liver\u2010brain\u2010eye Nanism\u00a0=\u00a0dwarfism), is an autosomal recessive disorder caused by mutations in the TRIM37 gene.c.493\u20102A>G has been reported in Finnish patients probably due to a founder effect.Mulibrey\u2010Nanism (MUL) and length of 49\u2009cm . On examination, child had a triangular face, low nasal bridge, high broad forehead, low set ears, a high\u2010pitched voice, distended abdomen, left sided ballotable renal mass and hepatomegaly. Neurological examination revealed mild hypotonia and normal higher mental functions. His present height was 87\u2009cm (15th\u201350th centile as per WHO growth chart) and weight was 10\u00a0kg (third centile as per WHO growth chart). Echocardiography showed moderate size secundum atrial septal defect (ASD) with bidirectional shunt predominantly left to right and restrictive filling of right ventricle as evidenced by tissue doppler imaging. Final diagnosis was considered WT stage 4 due to multiple nodules seen in liver. He was started on neo\u2010adjuvant chemotherapy as per SIOP2001 protocol.A 2\u2010year\u2010old boy presented with incidentally detected mass in left side of his abdomen. Computerized tomography (CT) scan of abdomen showed a heterogeneously enhancing, solid cystic lesion measuring 59\u2009\u00d7\u200956\u2009\u00d7\u200982\u2009mm in the upper pole of the left kidney. Liver was also enlarged with hypodense lesions in segments IVB/V and VI. CT chest showed no evidence of metastasis. Renal and liver biopsies were done at another center. Review of renal biopsy confirmed the diagnosis of WT. Liver biopsy showed no tumor. He was born of non\u2010consanguineous parents with birth weight of 2800\u2009g on electrocardiogram. It was aborted with injection amiodarone. Gradually his voice returned and he could swallow food. In view of cough, he was tested for SARS\u2010COV\u20102 by PCR and it was detected to be positive. He was shifted to COVID\u201019 care ward where he had a second episode of atrial flutter and required to be shifted to intensive care unit again. He was managed successfully for AF and his cardiac rhythm reverted to normal. Once he was negative for COVID\u201019 he was discharged.c.1336C>T resulting in a stop codon and premature truncation of the protein at codon 446 (p. Arg446Ter). This mutation was reported as a pathogenic variant for Mulibrey\u2010Nanism. Another heterozygous missense variation in exon 2 of the TRIM37 gene variant c.80T>A that results in the amino acid substitution of Glutamine for Leucine at codon 27 was detected but was analyzed to be of unknown significance.In view of child not tolerating chemotherapy well, having abnormal facies, cardiac anomaly, hepatomegaly and abnormal findings in MRI brain; it was suspected that child has some underlying syndrome. So, a karyotyping with standard 400\u2013450\u2009G banding technique was performed and it was reported as normal. Mitomycin C sensitivity testing was done on 72\u2009h PHA stimulated unsynchronized cultures to rule of Fanconi Anemia and was reported as normal. Finally a clinical exome sequencing using selective capture and sequencing of the protein coding regions of the genome/genes was performed. The library was sequenced to mean >80\u2013100\u00d7 coverage on Illumina sequencing platform. The sequences obtained was aligned to human reference genome (GRCh38.p13) using Sentieon aligner and analyzed using Sentieon for removing duplicates, recalibration and re\u2010alignment of indels.The genomic DNA samples of the parents were analyzed for the reported variants in TRIM37 gene using PCR followed by DNA sequencing. Mother was negative for both c.80T>A and c.1336C>T mutations and father was heterozygous for c.80T>A and negative c.1336C>T. Although the c.80T>A has been reported to be of unknown significance, parental testing has proven that it is inherited from father and the other known mutation is de novo. The child satisfied the clinical criteria for diagnosis of MUL due to presence three major criteria and two minor criteria . Along with heterozygous pathogentic mutation, the second heterozygous novel mutation could possibly be considered deleterious causing MUL in him.Positron emission tomography\u2010CT done after completion of 5\u2010weeks of chemotherapy showed reduction in size of renal tumor with multiple non\u2010FDG avid liver lesions. CT chest was suggestive of minimal cardiomegaly with basal areas of parietal pericardium showing evidence of early calcification. He underwent nephrectomy and histopathology was suggestive of favorable histology WT . Review of tissue block of liver lesions was not suggestive of WT metastasis and a possibility of benign hamartomas was kept. Post operatively tumor was classified as stage\u2010I. Figure\u00a04On review of literature, we found a total of 14 cases including one case of ours.MUL is associated with an increased frequency of benign and malignant tumors and also shows disturbed control of organ development. Karlberg et al. noted a total of 210 tumorous lesions in 66/89 Finnish patients (74%). The benign tumors included cysts, vascular abnormalities (peliosis), adrenal adenoma, parathyroid adenoma, thyroid goiter, pancreatic cystadenoma, renal angiomyolipoma, ovarian fibro thecoma and phaeochromocytoma. Thirteen of the 89 patients (15%) had a malignant tumor, such as WT, renal papillary carcinoma, thyroid papillary and medullar carcinoma, ovarian and endometrial carcinoma, acute lymphoblastic leukemia, Langerhans cell histiocytosis and carcinoid tumor.WT can be the first presentation, with MUL being diagnosed several years later as seen in three cases found in this review of literature. Children with WT should be assessed for possible syndromic association and be managed accordingly.Two out of 14 patients initially treated for WT, required pericardiectomy several years later. Our case also has early signs of pericardial thickening and may later require cardiac intervention. Although cardiac affliction is known, arrhythmia as a predominant symptom seen in our patient has not been described previously. Other features seen in patients associated with MUL and WTs included bone dysplasia, constrictive pericarditis requiring pericardiectomy, and massive ascites requiring repeated abdominocentesis.5Our patient presented with WT. In view of child not tolerating chemotherapy well, having abnormal facies, cardiac anomaly, hepatomegaly and abnormal findings in MRI brain; it was suspected that child has some underlying syndrome thus genetic testing was performed. Our patient showed three major signs and two minor signs as described by Karlberg et al., depicted in Table\u00a0MUL is associated with an increased frequency of benign and malignant tumors and also shows disturbed control of organ development. The association of TRIM37 mutations with increased risk of cancer indicates a pro\u2010survival process in TRIM37\u2010deficient tumor cells. Wang et al. reported interaction of lysosomal protein mTOR with TRIM37, leading to transcriptional activation of genes involved in lysosome biogenesis and macro autophagy/autophagy. Autophagy could be a way for the cell to survive the loss of TRIM37.c.80T>A noted in our patient was novel and has not been reported previously.c.1336C>T is a reported pathogenic variant and is probably de novo acquired in our patient.The missense variation in exon 2 of the TRIM37 gene variant The coexisting liver lesion which was initially considered as hepatic metastasis and was later diagnosed as benign liver hamartomas, emphasizes the need to look out for associated benign tumors. These patients are highly prone to tumorigenesis and careful diagnosis can help in assigning the correct stage and formulating relevant treatment protocol.Heart is the most frequently affected organ in MUL with constrictive pericarditis, myocardial hypertrophy and variable myocardial fibrosis constituting the main components of Mulibrey heart disease. Mariata et al. reported 49 adults with MUL heart disease, noted these patients to be highly susceptible to develop congestive cardiac failure and need for pericardiectomy in one third of the patients.WT although rare in children with MUL, is treatable. Our case highlights the need to watch out for cardiac arrhythmia in these patients. Although a lot could not be gathered form review of literature regarding treatment protocol, but it appears that these children tolerate standard treatment protocol well and can achieve remission.All authors have nothing to disclose.Conceptualization, K.U., D.T., M.S.S., A.Y., K.B., J.S., N.R., S.P.Y.; Methodology, K.U., D.T., D.G., M.S.S., A.Y., R.K., V.R., K.B., S.N., J.S., N.R., S.P.Y.; Investigation, K.U., D.T., M.S.S., R.K., V.R., M.S.D., K.B., S.N., J.S., N.R., S.P.Y.; Formal Analysis, K.U., M.S.S., A.Y., R.K., V.R., K.B., S.N., J.S., N.R., S.P.Y.; Resources, K.U., D.T., D.G., M.S.S., A.Y., V.R., M.S.D., S.N., J.S., N.R., S.P.Y.; Writing\u2014Original Draft, K.U., D.G., J.S., N.R., S.P.Y.; Writing\u2014Review & Editing, D.T., M.S.S., R.K., K.B., N.R., S.P.Y.; Visualization, K.U., D.T., M.S.S., A.Y., R.K., V.R., M.S.D., K.B., S.N., J.S., N.R., S.P.Y.; Supervision, R.K., V.R., K.B., N.R., S.P.Y.; Funding Acquisition, D.T., A.Y., R.K., K.B., S.N., J.S., N.R., S.P.Y.; Data Curation, K.U., D.T., D.G., M.S.S., A.Y., R.K., V.R., M.S.D., K.B., S.N., J.S., N.R., S.P.Y.; Project Administration, K.U., D.T., K.B., N.R., S.P.Y.; Software, K.U., D.T., D.G., M.S.S., A.Y., V.R., K.B., S.N., J.S., N.R., S.P.Y.; Validation, K.U., D.T., A.Y., R.K., V.R., K.B., S.N., J.S., N.R., S.P.Y.All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Institutional approval N/A. Informed consent of parent obtained."} +{"text": "Prunus takasagomontana Sasaki 1931 is a deciduous flowering cherry endemic to Taiwan island, China. Here, we first report the complete chloroplast genome of P. takasagomontana. The complete chloroplast genome of P. takasagomontana is 157,946\u2009bp in length, which is comprised of a pair of inverted repeat (IR) regions of 26,437\u2009bp, a small single-copy (SSC) region of 19,145\u2009bp, and a large single-copy (LSC) region of 85,927\u2009bp. A total of 129 genes are annotated, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA ribosomal genes. The phylogenetic analysis showed that P. takasagomontana is sister to P. serrulata var. spontanea. Prunus takasagomontana Sasaki 1931 (Rosaceae) is a wild flowering cherry endemic to Taiwan island, China . A voucher specimen (no. JDYY039) was deposited in the Herbarium of Zhejiang Academy of Forestry, Hangzhou, China . The genomic DNA was extracted from leaf samples using Hi-DNAsecure Plant Kit , and used to construct a short-insert (<800\u2009bp) paired-end sequencing library. Paired-end sequencing was performed on the HiSeq X Ten analyzer at Novogene Co. Ltd. . The chloroplast DNA sequences were manually adjusted using Geneious 2022.0.1 regions, a small single-copy region, and a large single-copy region. The chloroplast genome encoded a total of 129 genes, containing 84 protein-coding genes (PCGs), 37 tRNA genes, and eight rRNA ribosomal genes. Among these genes, 112 genes are single copy, while six PCGs, seven tRNA genes, and four rRNA genes in IR regions are duplicated.The size of the chloroplast genome of Prunus species were used to construct the phylogenetic tree to clarify the phylogenetic position of P. takasagomontana with two Malus species and one Spirea species as the outgroup. The maximum-likelihood (ML) was performed using PhyloSuite with 1000 bootstrap replicates (Zhang et\u00a0al. P. takasagomontana was sister to P. serrulata var. spontanea, and had a close relationship with P. takesimensis and P. maximowiczii (The complete chloroplast genome sequences of other 19 mowiczii .X. S. and DY. J. contributed to the conception. DY. J., X. S., and YG. L. designed the work and collected the plant materials. LF. Z., YG. L., and DY. J. performed experiments. DY. J., LF. Z., and YG. L. analyzed and interpreted the data. X. S., DY. J., and LF. Z. wrote the manuscript. All authors were involved in the final approval of the version to be published. All authors agree to be accountable for all aspects of the work.Collection and study of plant material were conducted according to the guidelines provided by the Zhejiang Academy of Forestry. Permission was granted by the National Natural Science Foundation of China."} +{"text": "However, our \u201clet quantum be quantum\u201d approach poses questions absent in Bohr\u2019s Copenhagen Interpretation that relied on the preexisting classical domain. Thus, one is now forced to seek preferred, predictable, hence effectively classical but ultimately quantum states that allow observers keep reliable records. Without such (i) preferred basis relative states are simply \u201ctoo relative\u201d, and the ensuing basis ambiguity makes it difficult to identify events . Moreover, universal validity of quantum theory raises the issue of (ii) the origin of Born\u2019s rule, einselection\u2014environment\u2014induced superselection)\u2014are still quantum. Therefore, unlike classical states that exist objectively, quantum states of an individual system cannot be found out by an initially ignorant observer through direct measurement without being disrupted. So, to complete the \u2018quantum theory of the classical\u2019 one must identify (iii) quantum origin of objective existence and explain how the information about objectively existing states can appear to be essentially inconsequential for them (as it does for states in Newtonian physics) and yet matter in other settings . I show how the mathematical structure of quantum theory supplemented by the only uncontroversial measurement postulate leads to preferred states. These (i) pointer states correspond to measurement outcomes. Their stability is a prerequisite for objective existence of effectively classical states and for events such as quantum jumps. Events at hand, one can now enquire about their probability\u2014the probability of a pointer state (or of a measurement record). I show that the symmetry of entangled states\u2014(ii) entanglement\u2014assisted invariance or envariance\u2014implies Born\u2019s rule. Envariance also accounts for the loss of phase coherence between pointer states. Thus, decoherence can be traced to symmetries of entanglement and understood without its usual tool\u2014reduced density matrices. A simple and manifestly noncircular derivation of (iii) quantum Darwinism allows observers to use environment as a witness\u2014to find out pointer states indirectly, leaving systems of interest untouched. Quantum Darwinism shows how epistemic and ontic (coexisting in epiontic quantum state) separate into robust objective existence of pointer states and detached information about them, giving rise to extantons\u2014composite objects with system of interest in the core and multiple records of its pointer states in the halo comprising of environment subsystems which disseminates that information throughout the Universe.Core quantum postulates including the superposition principle and the unitarity of evolutions are natural and strikingly simple. I show that\u2014when supplemented with a limited version of predictability (captured in the textbook accounts by the repeatability postulate)\u2014these core postulates can account for all the symptoms of classicality. In particular, both objective classical reality and elusive information about reality arise, via quantum Darwinism, from the quantum substrate. This approach shares with the Relative State Interpretation of Everett the view that collapse of the wavepacket reflects perception of the state of the rest of the Universe Contents\u00a01\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Introduction31.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Core Quantum Postulates......................................................................................................................................................................................... 31.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum States, Information, and Existence......................................................................................................................................................... 51.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Interpreting Relative States Interpretation............................................................................................................................................................. 71.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Preview....................................................................................................................................................................................................................... 9\u00a02\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Jumps and Einselection from Information Flows and Predictability102.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Repeatability and the Quantum Origin of Quantum Jumps.................................................................................................................................. 112.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Mixed States of the \u201cTarget\u201d...................................................................................................................................................................................... 132.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Predictability Killed the (Schr\u00f6dinger\u2019s) Cat........................................................................................................................................................... 152.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Records and Branches: Degenerate \u201cControl\u201d......................................................................................................................................................... 15\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Repeatability and Actionable Information................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0172.5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Pointer Basis, Information Transfer, and Decoherence.......................................................................................................................................... 192.6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Irreversibility of Perceived Events, or \u201cDon\u2019t Blame the 2nd Law\u2014Wavepacket Collapse Is Your Own Fault!\u201d...........................................212.6.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Classical Measurement Can Be Reversed Even when Record of the Outcome is Kept.......................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0212.6.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Measurement Can\u2019t Be Reversed when the Record of the Outcome is Kept......................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0222.7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Summary: Events, Irreversibility, and Perceptions................................................................................................................................................ 23\u00a03\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Born\u2019s Rule from the Symmetries of Entanglement243.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Envariance................................................................................................................................................................................................................... 263.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Decoherence as a Result of Envariance.................................................................................................................................................................... 273.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Swaps, Counterswaps, and Equiprobability............................................................................................................................................................ 283.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Born\u2019s Rule from Envariance..................................................................................................................................................................................... 313.4.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Additivity of Probabilities from Envariance.............................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0333.4.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Algebra of Records as the Boolean Algebra of Events.............................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0353.5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Inverting Born\u2019s Rule: Why Is the Amplitude a Square Root of the Frequency of Occurrence?....................................................................... 363.6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Relative Frequencies from Relative States............................................................................................................................................................... 393.7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Envariance\u2014An Overview........................................................................................................................................................................................ 413.7.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Implications and the Scope of Envariance: Why Entanglement? Why Schmidt States?......................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0413.7.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Towards the Experimental Verification of Envariance............................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a043\u00a04\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism454.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Mutual Information, Redundancy, and Discord..................................................................................................................................................... 484.1.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Mutual Information.....................................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0484.1.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Discord........................................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0504.1.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Evidence and Its Redundancy....................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0524.1.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Mutual Information, Pure Decoherence, and Branching States.............................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0544.1.5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Surplus Decoherence and Redundant Decoherence................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0564.1.6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Information Gained by Pure and Mixed Environments..........................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0574.1.7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Environment as a Communication Channel.............................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0584.1.8\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism and Amplification Channels.................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0594.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism in Action................................................................................................................................................................................. 594.2.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 C-Nots and Qubits......................................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0604.2.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Central Spin Decohered by Noninteracting Spins....................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0614.2.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism in a Hazy Environment..........................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0644.2.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism and Pointer States...................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0654.2.5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Redundancy vs. Relaxation in the Central Spin Model...........................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0684.2.6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism in Quantum Brownian Motion.............................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0714.2.7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Huge Redundancy in Scattered Photons..................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0744.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Experimental Tests of Quantum Darwinism........................................................................................................................................................... 784.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Summary: Environment as an Amplification Channel........................................................................................................................................... 80\u00a05\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism and Objective Existence: Photohalos and Extantons825.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Anatomy of an Extanton............................................................................................................................................................................................ 825.1.1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Extantons and \u201cThe Classical\u201d...................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0835.1.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Photohalos, Photoextantons, and Information Detached from Existence.............................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0845.1.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Photohalos and the Quantum Origins of Irreversibility.........................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0855.2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism and the Existential Interpretation....................................................................................................................................... 855.3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0From Quantum Core Postulates to Objective Classical Reality............................................................................................................................. 865.4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Extantons and the Existential Interpretation.......................................................................................................................................................... 875.5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Decoherence and Information Processing............................................................................................................................................................... 885.6\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Quantum Darwinism and \u201cLife as We Know It\u201d.................................................................................................................................................... 89\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Seeing Is Believing......................................................................................................................................................................................\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0905.7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Bohr, Everett, and Wheeler........................................................................................................................................................................................ 905.8\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Closing Remarks......................................................................................................................................................................................................... 92\u00a0References94Quantum mechanics is often regarded as an essentially probabilistic theory, where the random collapses of the wavepacket with probabilities governed by the rule conjectured by Max Born 1926) [926 [1] pThe aim of this review is to assess the progress made in the wake of the earlier developments (including in particular theory decoherence and einselection) since the beginning of this millennium. This includes the realization that selection of preferred states\u2014einselection of the pointer states usually justified using decoherence\u2014is a consequence of the tension between the linearity of quantum theory and the nonlinearity of copying processes involved in the acquisition of information. Derivation of Born\u2019s rule based on the symmetries of entangled quantum states shores up and simplifies foundations of quantum theory.Quantum Darwinism will be discussed especially carefully, but nevertheless with significant omissions that are inevitable in reviewing a rapidly evolving field. In such a case one is faced with a \u201cmoving target\u201d\u2014the most recent developments are inevitably either left out or treated only in the superficial manner (since assessing their impact on the future development of the field is difficult).We will also reconsider the status of the quantum measurement problem . I shallWe shall start by reviewing the assumptions\u2014postulates of quantum theory\u2014and by selecting from their textbook version core postulates that are consistent and can be used to address the issues usually dealt with via measurement axioms that are also included in the textbook presentations but are inconsistent with the quantum core. More detailed preview of the content of this review can be found at the end of this introductory section.quantum theory of the classical we shall develop. Two are very familiar:The difficulty of reconciling quantum determinism with quantum randomness is reflected in the postulates that provide textbook summary of quantum mechanics . We listThe state of a quantum system is represented by a vector in its Hilbert space\u00a0(i) Evolutions are unitary .(ii) quantum superposition principle and the unitarity of evolutions, and we shall often refer to them by citing their physical consequences. They provide an almost complete summary of the formal structure of the theory.They imply, respectively, the One more postulate should be added to (i) and (ii) to complete the mathematics of quantum mechanics:Quantum state of a composite system is a vector in a tensor product of the Hilbert spaces of its subsystems.(o) deterministic description of the evolution of an indivisible Universe, and the measurement problem disappears and gest see .ab initio classical. They do not abide by the quantum principle of superposition\u2014their evolutions need not be unitary. Therefore, according to Copenhagen Interpretation, the unitarity postulate (ii) does not apply to measurements, and the literal collapse can happen on the border between quantum and classical.Given this clash between the mathematical structure of the theory and the expectation of the literal collapse , one is tempted to accept\u2014following Bohr\u2014primacy of our immediate experience and blame the inconsistency of (iv) with the core of quantum formalism and (ii)) on the nature of the apparatus: Copenhagen Interpretation regards apparatus, observer, and, generally, macroscopic objects as Uneasy coexistence of the quantum and the classical postulated by Bohr is a challenge to the unification instinct of physicists. Yet, it has proven surprisingly durable.At the heart of many approaches to the measurement problem is the desire to reduce the relation between existence and information about what exists to what could have been taken for granted in a world where the fundamental theory was Newtonian physics. There, classical systems had real states that existed independently of what was known about them. They could be found out by measurements. Many initially ignorant observers could measure the same system without perturbing it. Their records would agree, reflecting reality of the underlying state and confirming its objective existence.Immunity of classical states to measurements suggested that, in classical settings, the information was unphysical. Information was a mere immaterial shadow of real physical states. It was irrelevant for physics.This dismissive view of information run into problems already when Newtonian classical physics confronted classical thermodynamics. Clash of these two classical theories led to Maxwell\u2019s demon, and is implicated in the origins of the arrow of time.The specter of information was haunting classical physics since XIX century. The seemingly unphysical shadowy record state was beginning to play a role reserved for the \u201creal\u201d state.Attempts to solve measurement problem often follow the strategy where the underlying state of the quantum system somehow becomes classical. Even decoherence can be, in a sense, regarded as a completely quantum version of such a strategy, with the effective classicality arising in the world that is fundamentally quantum. Other proposals assert supremacy of existence over information and suggest modifications of quantum evolution equations as discussed by Weinberg (2012) .It is conceivable that, one day, we may find discrepancies of quantum theory with experiments. However, evidence to date supports view that our Universe is quantum to the core, and we have to reconcile superposition principle, unitarity and their consequences\u2014illustrated, e.g., by the violation of Bell\u2019s inequality\u2014with our perceptions. Nonlocality of quantum states and other experimental manifestations of quantumness are here to stay.The strategy adopted by the program discussed in this review is to start with the core quantum postulates (o)\u2013(iii). They have the simplicity that rivals postulates of special relativity. Given this \u201clet quantum be quantum\u201d starting point we shall show how (and to what extent) both attributes of the familiar classical world\u2014objective existence and information about it\u2014emerge from the epiontic quantum substrate.The alternative to Bohr\u2019s Copenhagen Interpretation and a new approach to the measurement problem was proposed by Hugh Everett III, student of John Archibald Wheeler, over half a century ago \u2014\u201cWhy don\u2019t I, the observer, perceive such splitting, but register just one outcome at a time?\u201d\u2014is then answered by asserting that while the right-hand side of Equation 1.1) contains all the possible outcomes, the observer who recorded outcome #17 will (from then on) perceive \u201cbranch #17\u201d that is consistent with the outcome reflected in his records. In other words, when the global state of the Universe is .1 contaiThis \u201clet quantum be quantum\u201d view of the collapse is supported by the repeatability postulate (iii); upon immediate re-measurement, the same state will be found. Everett\u2019s assertion: \u201cThe discontinuous jump into an eigenstate is thus only a relative proposition, dependent on the mode of decomposition of the total wave function into the superposition, and relative to a particularly chosen apparatus-coordinate value...\u201d. is consistent with the core quantum postulates: In the superposition of Equation (1.1) record state basis ambiguity is not limited to the pointers of measuring devices or cats, which for Schr\u00f6dinger (1935) cNevertheless, (as Everett argued) axiom (v) is inconsistent with the spirit of the \u201clet quantum be quantum\u201d approach. Therefore, one might guess, he would not have been satisfied with the usual approach to decoherence and its consequences. Indeed, Everett attempted to derive Born\u2019s rule from the other quantum postulates. We shall follow his lead, although not his strategy which\u2014as is now known\u2014was flawed and Born\u2019s rule (v) from the core postulates (o)\u2013(iii). We shall then, in pointer states\u2014(iva), the business end of the collapse postulate. We will show that the nature of the information transfer\u2014nature of the coupling to the measuring device\u2014determines this preferred set, and that any set of orthogonal states will do. We will also see how these states are (ein)selected by the dynamics of the process of information acquisition, thus following the spirit of Bohr\u2019s approach which emphasized the ability to communicate the results of measurements. Orthogonality of outcomes implies that repeatedly measurable quantum observable must be Hermitian. We shall then compare this approach with a decoherence-based approach to pointer states and the usual view of einselection.We start with a derivation of the preferred set of Pointer states\u2014terminal states for quantum jumps\u2014are determined by the dynamics of information transfer. They define the outcomes independently of the instantaneous reduced density matrix of the system and of its initial state. Fixed outcomes define events, and call for the derivation of probabilities. In Given Born\u2019s rule and preferred pointer states one is still faced with a problem. Quantum states are fragile. An initially ignorant observer cannot find out an unknown quantum state without endangering its existence: Collapse postulate means that selection of what to measure implies a set of outcomes. Therefore, only a lucky guess of an observable could let the observer find out an unknown state without repreparing it. The criterion for pointer states implied by postulates (o)\u2013(iii) turns out to be equivalent to their stability under decoherence, and still leaves one with the same difficulty: How to find out an effectively classical but ultimately quantum pointer state and leave it intact?The answer turns out to be surprisingly simple: Continuous monitoring of The classical world we perceive consists predominantly of macroscopic objects. Bohr decreed their states were classical \u201cby fiat\u201d, so that information about them could be acquired without perturbing them, thus restoring classical independence of existence from information. We recognize instead that quantum theory is universal. States of macroscopic objects become effectively classical (as Bohr wanted), but as a consequence of decoherence and einselection. Objects are immersed in the decohering environment consisting of subsystems (such as photons). Superpositions of pointer states are unstable, quickly turning into their mixtures. Thus, predictably evolving quantum states of macroscopic objects are restricted to stable, effectively classical pointer states einselected by decoherence. In the course of decoherence fragments of the environment that monitors them become inscribed with the data about their pointer states.Extanton is a composite entity with the object of interest in its core embedded in the information-laden halo, part of the environment that monitors its pointer states. Information about them is heralded by the fragments of the environment, and disseminated throughout the Universe. Fragments of the halo intercepted by observers inform about the state of its core. Extanton combines the source of information (extanton core) with the means of its transmission .John Bell imagineExtantons are quantum, but fulfill these desiderata. Environment determines pointer states through einselection. Pointer states of extanton cores persist and the environment broadcasts information about them. That information reaches observers, revealing the pointer state of the macroscopic system at the extanton core without the need for direct measurement .We are immersed in such extaton halos, inundated with the information about pointer states in their cores. This is how the classical world we perceive emerges from within our quantum Universe.As we shall see, several steps based on interdependent insights are needed to account for quantum jumps, for the appearance of the collapse, for preferred pointer states, for the probabilities and Born\u2019s rule, and, finally, for the consensus, the essence of objective reality\u2014for the emergence of \u2018the classical\u2019 from within a quantum Universe. It is important to take these steps in the right order, so that each step is based only on what is already established. This is our aim, and this order has determined the structure of this paper: The next three sections describe three crucial steps. Nevertheless, each section can be read separately: Preceding sections are important to provide the right setting, but are generally not essential as a background. An overview of the resulting quantum theory of the classical is presented and the interpretational implications are discussed in This section shows how the core quantum postulates (o)\u2013(iii) lead to the discreteness we regard as characteristic of the quantum world. In textbooks this discreteness is introduced via the collapse axiom (iva) designating the eigenstates of the measured observable as the only possible outcomes. Here, we show that discontinuous quantum jumps between a restricted set of orthogonal states turn out to be a consequence of symmetry breaking that resolves the tension between the unitarity of quantum evolutions and repeatability. We shall also see how preferred Hermitian observables defined by the resulting orthogonal basis are related to the familiar pointer states.ad hoc lines of the Copenhagen Interpretation).Unitary evolution of a general initial state of a system We start with the same assumptions and follow similar steps, but arrive at a different conclusion. This is because instead of demanding a single outcome we shall only require that the result of the measurement can be confirmed (by a re-measurement), or communicated (by making a copy of the record). In either case, copying some state (of the system or of the apparatus) is essential. As \u201cperception\u201d and \u201cconsciousness\u201d presumably depend on copying and other such information processing tasks (as they undoubtedly do) then the necessity to deal with the Universe \u201cone branch at a time\u201d can produce symptoms of collapse while bypassing the need for it to be \u201cliteral\u201d.Amplification\u2014the ability to make copies, qmemes of the original\u2014is the essence of the repeatability postulate (iii). It calls for nonlinearity that would appear to be in conflict with the unitarity demanded by postulate (ii).As we shall see, copying is possible for orthogonal subsets of states of the original. Each such subset is determined by the measurement device\u2014by the unitary evolution that implements copying. When, beforehand, the system is not in one of such copying eigenstates, its state is not preserved. This shows why oneConsider a quantum system We now establish:Theorem\u00a01.The set of the unperturbed states Proof.\u00a0From the linearity implied by the unitarity of (ii) and Equation (2.1) we get, for an arbitrary initial state Equation (2.4) establishes postulate (iva)\u2014the orthogonality of the outcome states . As we have noted, (iva) is the essence, the \u201cbusiness end\u201d of the collapse axiom (iv). When the outcome states are orthogonal, any value of Note that\u2014as long as the state, Equation (2.1) is a direct product before and after the measurement\u2014this conclusion holds for an arbitrary initial state of The limitation of copying to distinguishable outcome states is then a direct consequence of the uncontroversial core postulates (o)\u2013(iii). It can be seen as a resolution of the tension between linearity of quantum theory (superpositions and unitarity of (i) and (ii)) and nonlinearity of the process of proliferation of information\u2014of amplification. This nonlinearity is especially obvious in cloning, as cloning in effect demands \u201ctwo of the same\u201d. The main difference is that in cloning copies must be perfect. Therefore, scalar products must be the same, Indeed, we can deduce orthogonality of states that remain unperturbed while leaving small but distinct imprints in theorem ,45,46) tevent. Wheeler [We now have a useful definition of an Wheeler \u2014followinEvents that get recorded repeatedly precipitate quantum jumps. They emerge\u2014as a consequence of the discreteness we have just deduced\u2014from within the quantum measurement setting where bAppearance of events in a pure state case prompts the question about their probabilities. If we were to proceed logically we would suspend discussion of how the core postulates (o)\u2013(iii) imply the essence of axiom (iv), derive Born\u2019s rule, and only then come back and consider how quantum jumps\u2014the essence of the collapse\u2014emerge in the mixed state case using the relation between pure states and reduced density matrices, the usual tools of decoherence. This course of argument would require a detour before we can come back and complete the discussion that we have already started.We shall avoid this, but we shall also avoid using probabilities and Born\u2019s rule, as in ,48. SomeWe also note that our tasks differ depending on whether mixed states of the control or mixed states of the target see are the qmeme\u2014of the essential information. This degeneracy is important in considering readout of information from a macroscopic apparatus pointer or any other macroscopic device that is supposed to keep reliable records [Generalization of our discussion to the case when the control\u2014the source of information\u2014is allowed to be in a mixed state must take into account an additional complication: The state of control can change, and yet result in the same copy\u2014a quantum meme or a records . ObviousEquations (2.1)\u2013(2.4) are based on idealizations that include purity of the initial state of Purification relates pure states and density matrices by treating some such pure state in the enlarged Hilbert space exists and that lack of purity of Indeed, there is no need to even mention There is also an alternative way to proceed that leads to the same conclusions but does not require purification. Instead, we assume at the outset that we can represent states as density matrices. Unitary evolution preserves scalar products, i.e., Hilbert-Schmidt norm of density operators defined by This conclusion can be reached even more directly: Obviously, In other words, in case of mixed target we can establish our key result using only pure states in an enlarged Hilbert space (purification), or only density matrices. The only reason one might want to invoke Born\u2019s rule is to provide a physically motivated bridge between these two representations of \u201cimpure\u201d states of The economy of our assumptions stands in stark contrast with the uncompromising nature of our conclusions: Predictability\u2014the demand that information transfer preserves the state of the system (embodied in postulate (iii))\u2014was, along with the superposition principle (i) and unitarity of quantum evolutions (ii)\u2014key to our derivation of the discreteness of states that can be repeatedly accessed. Discrete terminal states are behind the inevitability of quantum jumps.We shall see in There are several ways to describe our conclusions so far. To restate the obvious, we have established that repeatedly accessible outcome states must be orthogonal. This is the interpretation\u2014independent part of axiom (iv)\u2014all of it except for the literal collapse. The core quantum postulates alone make it impossible to find out preexisting quantum states.This is enough for the relative state account of quantum jumps\u2014collapse axiom (iv) is not necessary for that. So, a cat suspended between life and death cannot bAnother way of stating our conclusion is to note that a set of orthogonal states defines a Hermitian operator when supplemented with real eigenvalues. The above discussion is then a derivation of the Hermitian nature of observables. It justifies the focus on Hermitian operators often invoked in textbook version of measurement axioms .We note that \u201cstrict repeatability\u201d at the level of quantum systems is an idealization of a theorist , persisWe start by noting that one is almost never interested in the state of the apparatus as a whole: Finding out pure states of an object with Avogadro\u2019s number of atoms .Generalization to when the apparatus is in a mixed state can be carried out using purification strategy as before (this time purifying the \u201ccontrol\u201d In contrast to Equation (2.6) (where \u201ccontrol\u201d Previously we have modeled the acquisition of information about a system by a (possibly macroscopic) apparatus or by the environment in the course of decoherence. In either case \u201ctarget\u201d could be expected to be in a mixed state but the \u201ccontrol\u201d was pure. Now we are dealing with an apparatus acting as a macroscopic control. Its microscopic state is in general mixed, and can be influenced by the readout, but we still expect it to retain the record . This is possible because of degeneracy\u2014many microscopic states represent the same record.3state of the original to establish repeatability. Instead, we demand\u2014as a criterion for repeatable accessibility\u2014that; (i) the copies should contain the same information, and; (ii) that information should suffice to distinguish record This record should be repeatedly accessible and unambiguous. Before, in the discussion following Equations (2.1)\u2013(2.4), repeatability was assured by insisting that the state of the system\u2014of the control\u2014should remain unchanged during the readout. Now, we can no longer count on the preservation of the Above, we have seen how this demand can be implemented when the states of the memories actionable\u2014it should allow one to alter the state of a test system reductio ad absurdum reasoning that the ability to make multiple copies implies To address this question we propose an operational criterion: The information contained in each of the memories should be We have assumed above that there is no preexisting correlation between the test system and the rest, We also note that (as before) the whole argument can be recast in the language of the \u201cChurch of Larger Hilbert Space\u201d . That isussed in . The locWe conclude that only orthogonal projectors arise ntem, see .The reasoning behind the conclusions of this subsection parallels the pure states case, Equations (2.1)\u2013(2.4), but the mathematics and, above all, the physical motivation, differ. Before we were dealing with the abstract postulate of repeatability that is found in Dirac and otheIn a classical Universe repeatability is taken for granted, as an unknown classical state can be found out without endangering its existence. Repeatability in a quantum setting allows one to use fragile quantum states as building blocks of classical reality, as we shall see in more detail in In practice predictability and even repeatability are encountered not in the measured microscopic quantum system We have seen that the same condition of repeatability that led to orthogonality in the set of possible outcomes in the pure case of c, 1958) , this suevents. Our derivation above did not appeal to decoherence, but decoherence yields einselection . We will now see that einselection based on repeatability and einselection based on decoherence are in effect two views of the same phenomenon.We are now equipped with a set of measurement outcomes or, to put it in a way that ties in with the study of probabilities we shall embark on in what?\u201d. This in turn leads directly to the main issue addressed by einselection: \u201cWhat is the preferred basis?\u201d. This key question is often muddled in the \u201cfolklore\u201d accounts of decoherence.Popular accounts of decoherence and its role in the emergence of \u2018the classical\u2019 often start from the observation that when a quantum system The crux of the matter\u2014the reason why interaction with the environment can impose classicality\u2014is precisely the emergence of the preferred states. The basic criterion that selects preferred pointer states was discovered when the analogy between the role of the environment in decoherence and the role of the apparatus in a nondemolition measurement was recognized: What matters is that there are interactions that transfer information and yet leave some states of the system unaffected .The criterion for selecting such preferred states is persistence of correlation between two systems \u2013(iii). It leads to breaking of the unitary symmetry and singles out preferred states of the apparatus pointer (supplied in textbooks by axiom (iv)) without any need to invoke physical view of the reduced density matrices .This is important, as partial trace (understood as an averaging procedure) and reduced density matrices (understood as probability distributions) employed in decoherence theory rely on Born\u2019s rule . Our goal in the next section will be to arrive at Born\u2019s rule, axiom (v)\u2014to relate state vectors and probabilities. Obtaining preferred basis and deducing events without invoking density matrices and trace\u2014without relying on Born\u2019s rule\u2014is essential if we are to avoid circularity in its derivation.To compare derivation of the preferred states in decoherence with their emergence from symmetry breaking imposed by axioms (o)\u2013(iii) we return to Equation (2.2). We also temporarily suspend prohibition on the use of partial trace to compute reduced density matrix of the system:Resilience\u2014quantified by the ability to retain correlations in spite of the environment, and, hence, by persistence, as in Equations (2.4) and (2.7)\u2014is the essence of the original definition of pointer states and einselection ,25. SuchFor pure states this discussion of additivity can be carried out in a setting that is explicitly free of any reference to density matrices or trace, and relies only on correlations . Born\u2019s So, a piece of decoherence \u201cfolklore\u201d\u2014responsible for statements such as \u201cdecoherence causes reduced density matrix to be diagonal\u201d\u2014is at best imprecise, and often incorrect. The error is mathematical and obvious: Still, \u201cfolklore\u201d often assigns classicality to the eigenstates of h, 1990; ; 2007 [5h, 1990; ; Albrechh, 1990; , but seeh, 1990; ,57) and h, 1990; ). Howeveh, 1990; ,32,36: Tnonlocal ,60,61.Nonlocality of pointer states need not necessarily be a problem. The role of decoherence is to predict what happens\u2014what states are \u201cpointer\u201d given the physical context . Thus, testing it in situations when its predictions clash with our classical intuition is of interest . The pry sieve ,63) and and \u03c1S iy sieve ,43,49).,49.\u03c1S isAs is often the case with folk wisdom, a grain of truth is nevertheless reflected in such oversimplified \u201cproverbs\u201d: When the environment acquires perfect knowledge of the states it monitors without perturbing them, and Still, this coincidence should not be used to attempt a redefinition of pointer states as instantaneous eigenstates of Irreversibility has been blamed for the collapse of the wavepacket since at least von Neumann (1932) . The cauDiscrete quantum jumps occur as a consequence of the collapse. They are uniquely quantum, and a central conundrum of quantum physics. They reset the evolution relevant for the future of the observer putting it onto a course consistent with the measurement outcome (and prima facie at odds with the unitarity of quantum evolutions).We have just seen how the discreteness of quantum jumps follows from the quantum core postulates. We now point out that\u2014in addition to the \u201cusual suspects\u201d traditionally blamed for irreversibility\u2014there is a uniquely quantum reason why events associated with quantum jumps are fundamentally irreversible. It is distinct from the information loss associated with the dynamics that is responsible for the Second Law.gain (rather than its loss). It is noteworthy that quantum physics provides a uniquely quantum key that solves the distinctly quantum conundrum of the wavepacket collapse.This uniquely quantum source of irreversibility is a result of the information We shall see below that information about the measurement outcome does not preclude reversal of the classical measurement, but makes it impossible to undo evolution that leads to a quantum measurement whenever a superposition of the potential outcomes\u2014hence, the wavepacket collapse\u2014is involved.Let us first examine a measurement carried out by a classical agent/apparatus a), it is classical. Therefore, classical measurement can be undone simply by implementing The dynamics a). That is, the states of Our main point is that the reversal;ersal;2.asAsDs\u27f9ESConsider now a measurement of a quantum system repeatable measurement/copying on the states Note that unitary evolutions above implement When the information about the outcome is copied, the pre-measurement state We have now demonstrated the difference between the ability to reverse quantum and classical measurement. Information flows do not matter for classical, Newtonian dynamics. However, when information about a quantum measurement outcome is communicated\u2014copied and retained by any other system\u2014the evolution that led to that measurement cannot be reversed.Quantum irreversibility can result from the information gain rather than just its loss\u2014rather than just an increase of the (von Neumann) entropy. Recording of the outcome of the measurement resets, in effect, initial conditions within the observer\u2019s (branch of) the Universe, resulting in an irreversible, uniquely quantum \u201cwavepacket collapse\u201d. Thus, from the point of view of the measurer, information retention about an outcome of a quantum measurement implies irreversibility. Quantum states are epiontic.What the observer knows is inseparable from what the observer is: the physical state of the agent\u2019s memory represents the information about the Universe. The reliability of this information depends on the stability of its correlation with external observables. In this very immediate sense, decoherence brings about the apparent collapse of the wavepacket: after a decoherence time scale, only the einselected memory states will exist and retain useful correlations ,36,64,65Collapse is a consequence of einselection and of the one-to-one correspondence between the physical state of the observer\u2019s memory and of the information encoded in it. Memory is simultaneously a description of the recorded information and part of an identity tag, defining the observer as a physical system. It is as inconsistent to imagine an observer perceiving something other than what is implied by the stable (einselected) records as it is impossible to imagine the same person with a different DNA. Both cases involve information encoded in a state of a system inextricably linked with the physical identity of an individual.no information without representation [epiontic.Distinct memory/identity states of the observer cannot be superposed. This censorship is strictly enforced by decoherence and the resulting einselection. Distinct memory states label and inhabit different branches of Everett\u2019s many-worlds universe. The persistence of correlations between the records (data in possession of the observers) and the recorded states of macroscopic systems is all that is needed to recover objective classical reality. In this manner, the distinction between ontology and epistemology\u2014between what is and what is known to be\u2014is dissolved. There can be entation .Quantum The discreteness underlying \u201ccollapse of the wavepacket\u201d has a well-defined origin\u2014it resolves the conflict between the linearity of the unitary quantum evolutions and the nonlinearity associated with the amplification of information in measurements but also in the monitoring by the environment\u2014in decoherence. Any process that involves (even modest) amplification\u2014that leads to copies, qmemes of an \u201coriginal state\u201d \u2014demands orthogonality.Copying (as any other quantum evolution) is unitary, so it will not result in collapse. However, perception of the collapse will arise as a consequence of the irreversibility induced by the information transfer we have just discussed. This purely quantum irreversibility provides a mechanism for collapse of the wavepacket that was not available (and not needed) in the classical setting\u2014a mechanism that is fundamental, and uniquely quantum. The old question about the origins of irreversibility acquires a new quantum aspect especially apparent in the context of quantum measurements: Thus, while in the classical setting measuring of an evolving state of the system need not alter its evolution, in the quantum setting measurement derails evolution and redirects it onto the track consistent with the record made by the observer. One might say that a measurement re-sets the initial condition of the evolving quantum system .Thus, while the irreversible wavepacket collapse was sometimes blamed on the consciousness of the observer t,48 t35,4repeatability requires distinguishability. In a quantum setting of Hilbert spaces and unitarity of evolutions\u2014postulates (i) and (ii)\u2014this means that repeatability begets orthogonality. to assure repeatability\u2014ability to reconfirm what is known\u2014one must focus on mutually exclusive events represented by orthogonal states.From the point of view of axiom (v) and the rest of this paper the most important conclusion of the present section is that We end this section with a simple purely quantum definition of events in hand: Record made in the measurement resets initial conditions relevant for the subsequent evolution of the branch of the universal state vector tagged by that record. We now take up the question: What is the probability of a particular record\u2014specific new initial condition\u2014given the preexisting superposition of the possible outcome states.N possible distinct outcomes and the observer is ignorant of what will happen, all alternatives appear equally likely. Probability observer should then assign to any one outcome is principle of equal likelihood using invariance encapsulated in his \u2018principle of indifference\u2019: Player ignorant of the face value of cards .The first widely accepted definition of probability was codified by Laplace (1820) : When thof cards a will besubjective symmetry: Equal likelihood is a statement about observers \u2018state of mind\u2019 , and not a measurable property of the real physical state of the system . Indeedr (Stein ).all branches)\u2014in the limit of infinite and fictitious ensembles . Such ile, 1968 . As notele, 1968 ; Caves ale, 1968 ). It is le, 1968 and Squile, 1968 that theThe other way of dealing with this issue is to modify physics so that branches with small enough amplitude simply do not count \u2014bypasseGleason\u2019s theorem implemenobjective symmetry of known quantum states.We shall now demonstrate how quantum entanglement leads to probabilities based on a symmetry, but\u2014in contrast to subjective equal likelihood based on ignorance\u2014on an Schmidt decomposition of a pure entangled A pure entangled state of a system perfectly correlated outcomes of judiciously chosen measurements on each subsystem: Detecting vice versa.Schmidt decomposition demonstrates that any pure entangled bipartite state is a superposition of Even readers unfamiliar with Equation (3.1) have likely relied on its consequences: Schmidt basis ive envariance is an Entangled states might seem an unusual starting point for the study of probabilities. After all, the textbook statement of Born\u2019s rule deals with pure states of individual systems. Nevertheless, already in Schr\u00f6dinger\u2019s famous \u201ccat\u201d paper the discEntanglement is also the essence of decoherence responsible for the emergence of \u201cthe classical\u201d in a quantum Universe. It is therefore natural to investigate symmetries of entangled quantum states, and explore their implication for how much can be known about parts when the whole is entangled. In addition, as we shall see below, envariance allows one to reassess the role of the environment and sheds new light on the origin of decoherence.invariant under the change of phases of state of Envariance of entangled states leads to our first conclusion: Phases of Schmidt coefficients are envariant under local (Schmidt) unitaries, Equations (3.4). Therefore, when a composite system is in an entangled state We have just seen that the loss of phase coherence between Schmidt states\u2014decoherence\u2014is a consequence of envariance: Decoherence is, after all, a selective loss of relevance of phases for the state of However, decoherence viewed from the vantage point of envariance may look unfamiliar. What other landmarks of decoherence can we find without using trace and reduced density matrices ? The answer is\u2014all the essential ones ,48,49. Wherence , but sucAssuming decoherence to get ek, 1998 ; Deutschek, 1998 ; Wallaceek, 1998 ) would mek, 1998 ,88,89,90As perceptive analysis by Drezet (2021) shows, epure classical states are never envariant.Envariance of pure states is purely quantum: Classical state of a composite classical system is given by a Cartesian (rather than tensor) product of its constituents. Therefore, to completely know a state of a composite classical system one must know a state of each subsystem. It follows that when one part of a classical composite system is affected by a transformation\u2014a classical analogue of a swap However, a mixed state can mimic envariance: When we only know that a dime and a nickel are \u2018same side up\u2019, we can \u2018undo\u2019 the effect of the flip of a dime by flipping a nickel. This classical analogue depends on partial ignorance: To emulate envariance, we cannot know individual states of the two coins\u2014just the fact that they are the same side up\u2014just their correlation.implies equal probabilities for any orthonormal set of states In quantum physics, tensor structure of states for composite systems means that \u2018pure correlation\u2019 is possible. We shall now prove that a maximally entangled \u201ceven\u201d state with equal absolute values of Schmidt coefficients:even state is envariant under a swap operationSuch an wo cards . It is acounterswap on A swap on prove that probabilities of envariantly swappable outcome states must be equal. But let us proceed with caution: Invariance under a swap is not enough\u2014probability could depend on some other \u2018intrinsic\u2019 property of the state. For instance, in a superposition energies of We want to Fact 1:Unitary transformations must act on a system to alter its state. That is, when an operator does not act on the Hilbert space Fact 2:The state of the system Fact 3:The state of a larger composite system that includes Envariance can be used to prove that this cannot happen\u2014that probabilities of envariantly swappable states are indeed equal. To this end we first define what is meant by \u201cthe state\u201d and \u201cthe system\u201d more carefully. Quantum role of these concepts is elucidated by three \u201cFacts\u201d\u2014three definitions that recognize what is known about systems and their (mixed) states, but phrase it in a way that does not appeal to the Born-rule dependent tools and concepts :Note that the states defined this way need not be pure. In addition, note that Facts\u2014while \u2018naturally quantum\u2019\u2014are not in conflict with the role of states in classical physics.prove:Facts are a consequence of quantum theory. They are not, in any sense, additional assumptions. Rather, they clarify operational meanings of concepts (such as \u201ca state\u201d) that will play key role in the derivation of Born\u2019s rule: Facts are the attributes that any sensible notion of a \u201cstate\u201d should possess. They also help distinguish purely quantum view based on the core quantum postulates from, e.g., hidden variable theory .We can now Theorem\u00a02.When Schmidt coefficients satisfy Proof.\u00a0Swap changes partners in the Schmidt decomposition . However, when the coefficients of the swapped outcomes differ only by a phase, a swap can be undone allows us to get rid of such subjectivity altogether. The simplest way to prove the desired equality of probabilities is based on perfect correlation between the Schmidt states of swapping Schmidt states of\u00a0exchanges their probabilities, and when the state is even it also keeps them the same! This can be true only when the probabilities of envariantly swappable states are equal.We now focus on an even state, Equation (3.5). It is envariant under all local unitaries . Thus (by Fact 1) the state of We can now state our conclusion:Corollary\u00a01.When all N coefficients in the Schmidt decomposition have the same absolute values (as in the even states of Equation (3.5)), probability of each Schmidt state must be the same, and, therefore, by normalization, it is Readers may regard this as obvious, but (as recognized by Barnum (2003) , SchlossStill, this may seem like a lot of work to arrive at something seemingly obvious: The case of unequal coefficients is our next goal. However\u2014as we will see\u2014it can be reduced to the equal coefficient case we have just settled. The symmetry of entanglement inherent in the equal coefficients case provides the crucial link between the quantum state vectors and the experimental consequences. Simple algebra along with the special case of probability\u2014certainty\u2014will lead us directly to Born\u2019s ruleWe emphasize that in contrast to many other approaches to both classical and quantum probability, our envariant derivation is based not on a subjective assessment of an observer, but on an objective, experimentally verifiable symmetry of entangled states. Observer is forced to conclude that probabilities of local outcomes are equal not because of subjective ignorance, but because of certainty about something else: Certainty about the symmetries of the global state of the composite system implies\u2014via symmetries of entanglement encapsulated in envariance\u2014that local Schmidt states are equiprobableN equiprobable alternatives leads to Envariant probability is also a probability of an individual event\u2014there is no need for an ensemble of many events, so that relative frequency of \u201cfavorable\u201d events can be used to define probability. Rather, we are decomposing the future possibilities into equiprobable alternatives, and deducing probability from the ratio of the number of favorable alternatives to the total. Above, just one favorable out of To illustrate general \u201cfinegraining\u201d strategy of reducing cases with unequal coefficients to the previously described equal coefficient case for its To reduce this case to an even state we extend \u201cuneven\u201d Clearly, for joint states Note that above we have avoided assuming additivity of probabilities: Bypassing appeal to additivity of probabilities is essential in interpreting theory with another principle of additivity\u2014quantum superposition principle\u2014which trumps additivity of probabilities or at least classical intuitive ideas about what should be additive . Here, this conflict is averted: Probabilities of Schmidt states can be added because of the loss of phase coherence that follows directly from envariance, as we have established earlier, and as was discussed in . We retuConsider now a more general case of arbitrary coefficients. For simplicity we focus on entangled state with just two non-zero Schmidt coefficients:As before, the strategy is to convert a general entangled state into an even state, and then to apply envariance under swaps. To implement it, we assume s stands for 0 or 1, as needed) in the composite system Envariance we need is associated with counterswaps of a priori imposition of symptoms of classicality that would violate the spirit of quantum theory.In contrast with other approaches, probabilities in our envariant derivation are a consequence of complementarity, of the incompatibility of the purity of the entangled state of the whole with the purity of the states of parts. Born\u2019s rule appears in a completely quantum setting, without any Envariant derivation does not require additivity as an assumption: The strategy that bypasses appeal to additivity used in the simple case of Equation (3.10a) can be generalized . The asassume additivity of probabilities. This assumption is motivated by the assertion that probability is a measure. On the other hand, in the standard approach of Laplace (1820) [Kolmogorov\u2019s axiomatic formulation of the probability theory as welle (1820) additivie (1820) ). The keobjective symmetries \u2014that envariantly swappable events are equiprobable. We can now follow Laplace\u2019s strategy and use equiprobability along with decoherence already justified directly by envariance the probability of a composite event:Phases between the record (pointer) states do not influence the outcome of any local measurement that can be carried out on the apparatus (or on decohered records in the memory of the observer). This independence of the local state from the global phases in the Schmidt decomposition invalidates the principle of superposition when the system of interest are \u2018open\u2019, entangled with their environments. Therefore, we can now Lemma\u00a01.Probability of a composite (coarse-grained) event consisting of a subsetof is given by:To prove additivity of probabilities using envariance we consider the state:We first note that the form of N envariantly swappable outcome states, and they exhaust all of the possible outcomes, each should be assigned probability of To establish this Lemma we exploit basic implications of envariance: When there are total Proof.\u00a0Proof of the Lemma starts with the observation that probability of any composite event Corollary\u00a02.Probability of mutually compatible exclusive events Note that in establishing additivity Lemma we have only considered situations that can be reduced to certainty or impossibility . This is in keeping with our strategy of deriving probability and, in particular, of arriving at Born\u2019s rule from certainty and symmetries.Algebra of events can be Theorem\u00a03.Events corresponding to the records stored in the memory pointer states define a Boolean algebra.Proof.\u00a0(a)Commutativity:(b)Associativity:(c)Absorptivity:(d)Distributivity:(e)Orthocompletness:To show that the algebra of records is Boolean we need to show that coarse\u2014grained events satisfy any of the sets ofProofs of (a)\u2013(e) are straightforward manipulations of projection operators. We leave them as an exercise to the interested reader. As an example we give the proof of distributivity: These record projectors commute because records are associated with the orthonormal pointer basis of the memory of the observer or of the apparatus: It is impossible to consult memory cell in any other basis, so the problems with distributivity pointed out by Birkhoff and von Neumann simply do not arise\u2014when records are kept in orthonormal pointer states, there is no need for \u2018quantum logic\u2019.Theorem 3 entitles one to think of the outcomes of measurements\u2014of the records kept in various pointer states\u2014in classical terms. Projectors corresponding to pointer subspaces define overlapping but compatible volumes inside the memory Hilbert space. Algebra of such composite events (defined as coarse grained records) is indeed Boolean. The danger of the loss of additivity (which in quantum systems is intimately tied to the principle of superposition) has been averted: Distributive law of classical logic holds.The strategy we have pursued above to derive Born\u2019s rule for unequal coefficients was to consider two different splits, This reasoning can be reversed: We shall now use the strategy of moving the line dividing the two subsystems of interest in a tripartite composite system to show that the amplitudes must be proportional to the square roots of the frequencies of occurrence of the corresponding events.m 1\u2019s in a measurement by an apparatus M identical copies:We consider the probability of getting a count of k\u2019s member of the ensemble, as such a swap can be undone by a counterswap m detections of \u201c1\u201d, that is;We shall work with the case of m 1\u2019s must be proportional to m detections of 1.The number of distinct outcome sequence states in m 1\u2019s to the amplitude of the corresponding state. We prepare to address this question by adding a quantum system that counts 1\u2019s and enters their number in the registerWe now relate probability of a specific count of m to the amplitude of the corresponding state We shall now use envariance of m 1\u2019s determines the norm of mathematical operation that converts Normalizing states of m is given by the fraction of such sequences. That is:It is now easy to see that states;m 1\u2019s\u2014is proportional to the square root of the number of equiprobable sequences that lead to that count;square roots of relative frequencies\u2014to the square roots of the cardinalities of subsets of m\u2019 of composite events. In a sense, our calculation \u201cinverts\u201d the derivation of Born\u2019s rule we have presented before.Indeed, Equation (3.23b) is a coarse-grained version of Equations (3.22) and (3.23a). So, the above expression for As in the earlier derivation of Born\u2019s rule, the key was to express the same tripartite global state m is an \u201cevent of interest\u201d, but now its probability can be deduced from m.The location of the border between the two parts of the whole Generalization to when We shall now use envariance to deduce relative frequencies from amplitudes. In view of the discussion immediately above the relation between amplitudes and frequencies is already apparent, so this may seem superfluous, but we shall sketch it anyway \u201cfor the sake of completeness\u201d, and also because it provides a different\u2014experimentally motivated, one could say\u2014point of view of the alternatives. A much more complete derivation of relative frequencies from envariance is also available in Ref. .We emphasize that we do not need relative frequencies to define probabilities: Probabilities are already in place. They are \u201csingle shot\u201d, defined not by counting the number of \u201cfavorable events\u201d (as in the relative frequency approach), but, rather, by first establishing equiprobability of a certain class of events, and then by counting the number of equiprobable favorable possibilities. Therefore, the calculation immediately below is, in a sense, only a consistency check.M distinguishable m 1\u2019s. The answer is clearly, m 1\u2019s in M trials is given by:M is large, not because envariant derivation requires this\u2014we have already obtained Born\u2019s rule for individual events, Consider es, 1939 ; Gnedenkes, 1939 ). In thaad hoc assumptions that relate size of the coefficients in the global state to probabilities [The average number of 1\u2019s is, according to Equation (3.29), ch 1984) ), or modch 1984) ; Buniy, ch 1984) ), or on ch 1984) ; Farhi, ch 1984) ). Such sch 1984) ; Kent, 1ch 1984) ; Squiresch 1984) ; Joos, 2ch 1984) ; Aulettach 1984) ).and size of the coefficients) that derailed previous relative state attempts. We simply count the number of envariantly swappable (and hence provably equiprobable) sequences of potential events. This settles the issue of \u201cmaverick universes\u201d\u2014atypical branches with numbers of e.g., 0\u2019s very different from the average Note that we avoid the problem of two independent measures of probability or by aEnvariance settles a major outstanding quantum foundational problem: The origin of probabilities. Born\u2019s rule can be now established on a basis of a solid and simple physical reasoning, and without assuming additivity of probabilities . We havThere were other attempts to apply Laplacean strategy of invariance under permutations to prove \u201cindifference\u201d. This author noted thHowever, a reduced density matrix is not the right starting point for the derivation: A pure state, prepared by the observer in the preceding measurement, is. In addition, to get from such a pure state to a mixed (reduced) density matrix one must \u201ctrace\u201d\u2014average over, e.g., the environment. Born\u2019s rule is involved in averaging, which leads to a concern that such a derivation may be circular ,35,48,88not the overall phase. Indeed, orthogonal to One could attempt to deal with a pure state of a single system instead. Deutsch (1999) and his ad hoc [The other problem with decision theory approaches put forward to date is selection of events one of which will happen upon measurement\u2014the choice of the preferred states. These two problems must be settled, either through appeal to decoherence , which th, 1999) by interh, 1999) \u2014employs h, 1999) ,48,89,90In more recent papers, advocates of the decision theory approach adopt a strategy that inEnvariant derivation of Born\u2019s rule we have presented is an extension of the swap strategy in . HoweverEnvariance leads to Born\u2019s rule, but also to new appreciation of decoherence. Pointer states can be inferred directly from the dynamics of information transfers as was shown in any basis that spans Envariance is firmly rooted in quantum physics. It is based on the symmetries of entanglement. One may be nevertheless concerned about the scope of envariant approach: Envariance of Schmidt coefficient phases is closely tied to the einselection of pointer states: After decoherence has set in, pointer states diagonalize reduced density matrices nearly as well as the Schmidt states . Residual misalignment is not going to be a major problem. At most, it might cause minor violations of the laws obeyed by the classical probability for events defined by the pointer states.Such violations are intriguing, and perhaps even detectable, but unlikely to matter in the macroscopic setting we usually deal with. To see why, we revisit pointer states\u2014Schmidt states (or einselection\u2014envariance) link in the setting of measurements: Observer ek, 1991 , 2003 [7ek, 1991 ; Schlossek, 1991 ; 2007 [3ek, 1991 ). This sApparatus is built to measure a specific observable of the apparatus can be outcomes.To answer questions we started with , entanglement is a result of interactions that cause measurement and decoherence, and only pointer states This emphasis on the role of the apparatus in deciding what happens parallels Bohr\u2019s view captured by \u201cNo phenomenon is a phenomenon until it is a recorded phenomenon\u201d . In our Envariant approach applies even when can be interpreted envariantly.Other simplifying assumptions we invoked can be also relaxed . For exanner see . Given tbefore he or she finds out the measurement outcome. Therefore, envariant probabilities admit ignorance interpretation\u2014future outcome . Of course, once Probabilities described by Born\u2019s rule quantify ignorance of the observer Envariant approach uses incompatibility between observables of the whole and its parts. It has been now adopted and discussed by others test uses pairs of entangled photons to perform the requisite transformations . The finEnvariance was indeed confirmed with impressive accuracy. Aware of the dangers of circularity Vermeyden et al. used Bhattacharyya coefficient to analyze the experimental data. They have also tested (and constrained) the theory of Son (2014) which alThe experiment of Harris et al. (2016) verifiedThe advent of quantum computers has allowed theorists to act as experimenters. A pioneering example is the test of envariance using 5 qubits of IBM\u2019s Quantum Experience carried out by Deffner (2016) . In addiWhile present day quantum computers are imperfect, the progress is, of recent, relatively rapid. It seems therefore likely that much more accurate implementations of strategies that test this fundamental symmetry as well as more advanced tests should be within reach soon. A possible circuit that can be used to verify envariance is illustrated in In the meantime, it may be useful to consider other experimental settings and other designs that require laboratory tests but that allow one to verify that (in the wake of a swap and a counterswap) nothing happens that the global state is restored. A possible design of such a test that employs Hong-Ou-Mandel (HOM) interferometry \u201csole responsibility\u201d of the system.Quantum states can, in effect, exist objectively\u2014retain their identity and result in compatible records of independent measurements by many observers\u2014providing observers measure only observables that commute with the preexisting state of the system. In the aftermath of decoherence, this means restriction to its pointer observable. In that case, observers will agree about the outcomes\u2014their measurements will not invalidate one another and will not be erased by decoherence. Therefore, a consensus about the state based on independent measurements\u2014the essence of objectivity\u2014can be established. Such a consensus is the only operational requirement for the \u201cobjective existence of classical reality\u201d in our quantum Universe. However, why should observers measure only pointer observables?witness to the pointer state of the system.Quantum Darwinism provides a simple and natural explanation of this restriction, and, hence, of objective existence\u2014bulwark of classicality\u2014for the einselected states. Quantum Darwinism recognizes that the information we acquire about the Universe comes to us indirectly, through the evidence systems of interest deposited in their environments, and that the only states capable of depositing multiple copies\u2014many quantum memes or qmemes\u2014are the einselected pointer states. Observers access directly only the record made in a fraction of the environment\u2014an imprint of the original state of In this section we define mutual information, and use it to characterize the information that can be gained about The multiplicity of records of the pointer observable of The system itself is untouched\u2014it is not measured directly. Observers acquire their information indirectly, from the qmemes in the environment that has \u201cmeasured\u201d the system while decohering it. What we find out about our quantum Universe as a consequence of decoherence (that restricts stable states of macroscopic systems to the einselected pointer states) and of quantum Darwinism (selective proliferation of the information about these pointer states). What we see looks classical\u2014it is our familiar classical world: Environment communicates information about pointer states that were selected by decoherence.We perceive our reality as classical because we are immersed in the information bearing halos of macroscopic systems\u2014because our world consists of extantons, composite entities that combine the source of information (the pointer observable of the macroscopic object that resides in the extanton core) with the means of its delivery . We only pay attention to the message (the state of the extanton core) and take for granted\u2014ignore\u2014its means of delivery .Fragility of individual quantum states is no longer a problem. Observers will generally destroy the evidence while acquiring information. However, there are now many copies of the same information\u2014all imprinted with the data about the underlying state of the system. Therefore, even though evidence of the state of the system may be in part erased, consensus about it will emerge in the end, even as observers measure different fragments of the environment in ways that obliterate carriers of that information.Last not least, even when observers do not know what are the pointer states of the system, the environment does, and will let them know: Consensus between the evidence carried by different fragments of quantum theory of the classical. Derivation of the pointer states via repeatability in amplification channel\u2014a quantum communication channel that carries multiple qmemes of the classical information about the \u2018events\u2019 corresponding to the pointer states of Quantum Darwinism can be developed starting from the same assumptions as decohrence theory. Nevertheless, results of the two previous sections are essential when one aims to arrive at a consistent and comprehensive The inevitable price of the amplification of the preferred observable is the destruction of the information about the complementary observables and about the initial superposition of the pointer states of To make these ideas rigorous we shall calculate the number of copies of of E see using reQuantities that play key role in quantum Darwinism are often expressed in terms of the von Neumann entropy:As was done (since at least Laplace) classically, probabilities underlying quantum von Neumann entropy can be regarded as a measure of ignoranceWhat is the ignorance of someone interested in an observable with states H to denote both von Neumann and Shannon entropy. Sometimes different letters are used for this purpose. We will not do that because, to begin with, Note that above\u2014in Equations (4.1) and (4.2)\u2014we have used the same Mutual information will help us find out how much a fragment of the environment knows about the system, and what does it know. It is the difference between entropy of two systems treated separately and jointly:For classical systems the above definition of conditional density matrix describing the state of the system given the measurement outcome\u2014e.g., given the state In classical settings, when states can be characterized by probability distributions, one can simply substitute either of the Equations (4.5) for Once the observer perceives the outcome, the relevant state of This increase of entropy is characteristically quantum. It was pointed out already by von Neumann (1932) . DecoherThe entropy in Equation (4.8) can be viewed as a half von Neumann\u2014half Shannon: It involves (quantum) conditional density matrices as well as probabilities of outcomes. Given We shall find uses for all of these variants of mutual information. The von Neumann entropy based With the help of Equation (4.8) one can define \u201chalf way\u201d (Shannon\u2014von Neumann) mutual informations that presume a specific measurement on one of the two systems , and one of the half-way Shannon\u2014von Neumann versions ,125,126.Discord is asymmetric and basis-dependent, as information gain about ximation .I ) and the asymmetric J ) coincide. The proof [When the composite system is classical, so that its state can be found out without disturbing it and can be\u2014prior to measurements\u2014characterized by a probability distribution that is independent of the measuring process, the symmetric s, 1991) relies oJ is indeed asymmetric\u2014it depends on whether measurements are carried out on J results, courtesy of Bayes\u2019 rule, in a symmetric mutual information, as We emphasize that the asymmetric \u201chalf way\u201d (Shannon\u2014von Neumann) mutual information As a consequence of asymmetry between the system that is measured and its partner whose state is inferred indirectly, based on the outcome of that measurement, it is possible to have correlations that are classically accessible only \u201cfrom one end\u201d . For inse from A .Minimization used in Equation (4.13b) raises the obvious question: Could one do better if one used positive operator valued measures (POVM\u2019s) rather than Hermitian observables with orthogonal eigenstates? The answer is, unsurprisingly, \u201cYes\u201d. In the case of POVM\u2019s vo, 1973 ):(4.12c)k (2013) point ou, (2022) show thaQuantum discord has become an active area of research following indications that the \u201cquantumness\u201d it defines may play a fundamental role in operation of quantum thermodynamic demons redundancy of information . Discord will turn out to be a measure of the unattainable quantum information that cannot be extracted by local measurements from the fragments of the environment.One might be concerned that having different measures\u2014different mutual informations\u2014could be a problem, as this could lead to contradictory answers, but in practice this never becomes a serious issue for two related reasons: There is usually a well-defined pointer observable that obviously minimizes discord, so various possible definitions of mutual information tend to agree where it matters. Moreover, the effect we are investigating\u2014quantum Darwinism\u2014is not subtle: We shall see thet there are usually many copies of pointer states of . (2022) and Zwol. (2022) ) the disinformation deficit\u00a0We study a quantum system tems see . To be mWe now define redundancy as the number of fragments that can independently supply almost all\u2014all but \u03b4)HS see . Thus, tExamples of partial information plots (or \u201cPIPs\u201d) of the von Neumann mutual information for a pure composite system consisting of SE pure .There is a striking difference between the character of PIPs for random pure states in the whole joint Hilbert space classical information\u00a0quantum information that is locally inaccessible, but is present, at least in principle, in the global observables of the whole The character of such decoherence\u2014generated PIPs suggest dividing information into (i) easily accessible branching structure;This shape of PIPs is a result of einselection: When there is a preferred observable in pure decoherence that results in perfect branching states\u2014calculations simplify [In quantum Darwinism, fragment simplify ,145,146)Pure decoherence is defined by the system-environment Hamiltonian that commutes with We now consider evolution of ek, 2007 ; Zwolak,ek, 2007 ; 2010 [1ek, 2007 ):(4.20)IThe first contribution, f, The second term, k, 2010) to be thTo sum up, the initial climb of In addition to the need for global measurements there is another reason that suggests that In the case of initially pure f is nearly 1. However, even now In the \u201copposite\u201d case\u2014when surplus decoherence, so that one does not need all of In realistic situations, observers can intercept only a fraction of the environment. Thus, The essence of surplus decoherence is easily traced (and closely tied) to the branching structure of the states of redundant decoherence.Quantum Darwinism recognizes that situations when there are many copies of decoherence deficitRedundant decoherence may sound like an oxymoron\u2014once coherence is lost from f starting at 0 until Further simplifications of Equation (4.20) are often possible. Thus, when the environment is initially pure, we get:The opposite case of a completely mixed see Ref. ), in spiOne might be surprised that completely mixed environments can be effective decoherers. After all, decoherence is caused by the environment \u201cfinding out\u201d about the system, and in a completely mixed environment there does not seem to be any place left to accommodate the data. The right way of thinking about this relies on the \u201cChurch of Larger Hilbert Space\u201d view of the mixtures, and is very much in tune with the envariant derivation of probabilities and Born\u2019s rule in the preceding section. Mixed environment can be regarded as one half of an entangled pair (so that probabilities are due to the symmetries of entangled state involving The last case (that will be relevant for some of the examples we are about to consider) assumes initially pure This last equality allows one to use standard tools of decoherence to compute We conclude this section by noting that the way in which the information about vo, 1973 and Schuvo, 1973 ) shows tOne can rewrite the definition of quantum discord as:k, 2013) providescan show that theWe can now understand why only the pointer observable can be found out by intercepting a fraction of the environment. Redundant imprinting of an observable ragments ,130,149.The usual focus of the communication theory is to optimize the channel capacity. Thus, in quantum communication theory one would consider messages . QuantumWe shall now illustrate these insights in models of quantum Darwinism. We shall also investigate situations where some or even all of the simplifying assumptions employed above break down. We also note that the above discussion focused on the mutual information defined via von Neumann entropy, and thus, that it prepared us to answer the question about the amount of information that was deposited in, and can be extracted from dynamics responsible for decoherence is capable of imprinting multiple copies of the information about the system in the environment. Whether that environment can serve as a useful witness depends on the memory space it has available to store this information, and whether the information is stored unscrambled and unperturbed and is accessible to observers.Dissemination of information throughout the environment has not been analyzed until recently. Given the complexity of this process, it is no surprise that the number of results to date is still rather modest, but they have already led to new insights into the nature of the quantum-to-classical transition. The models discussed here show that; (i) Quantum Darwinism will always lead to decoherence, but the reverse is not true: There are situations where the environment cannot store any information about redundancy can keep on increasing long after decoherence has completely decohered the system: Copies of the einselected pointer observable can continue to be added\u2014imprinted on So, redundancy of records that is so central to quantum Darwinism is not necessarily implied by decoherence. Moreover; (ii) only the einselected pointer states can be redundantly recorded in While multiple copies of the information about the preferred pointer observable are disseminated throughout Last not least; (iii) Using imperfect analogies with classical devices, one can say that the information flow from In addition to these general characteristics of quantum Darwinism we shall see that realistic models\u2014e.g., photon scattering\u2014can lead to huge redundancies, and that environment that is partially mixed can still serve as an effective communication channel, allowing many observers independent access to the information about the preferred observable of the system.N) target qubits that constitute subsystems of the environment interacting via a controlled not (\u201cc-not\u201d) with a single control qubit k\u2019th c-not is carried out, The simplest model of quantum Darwinism is a rather contrived arrangement of many ,157156,1c-not\u2019s and qubits, this is no surprise.Hamiltonian of Equation (4.31a) provides an example of pure decoherence. It can imprint many copies of the preferred observable c-not\u2019s: A steep rise (where in accord with Equations (4.20) and (4.24), every bit of information stored in Copies of the pointer states of f near 0 or near 1 mutual information is approximately linear in f, see f turns out to be more complicated in exactly solvable models [In a central spin model with a large, initially pure and receptive environment and for a small information deficit ximately :(4.32)I .When In the discussion above We conclude that, when only a part of the Hilbert space of the environment subsystem is available to record the state of the system h, the preexisting entropy, instead of its maximal memory Inaccessibility of the memory of t causes ,153,158.h. This was necessary because the principal effect of a mixed environment is to lower the slope of the initial part of PIP\u2019s by In the manageable case of a single qubit system, dE works , although was, to begin with, closer to The results for a central spin k, 2010) . This chc-not\u2019s and qubits, the system decoheres as soon as a single copy of its state is imprinted with a reasonable accuracy in As we have seen before with What information is redundantly acquired by ek, 2004 ; 2005 [1ek, 2004 ).A natural way to characterize such correlations is to use the mutual information between an observable typical\u00a0completeness prerequisite for objectivity: All missing information about The information about observable information must be redundant.As a consequence of the basis ambiguity, information about many observables ironment ,25. TherTo quantify redundancy, we count the number of copies of the information about completely, redundantly, The key question now is: What is the structure of the set Theorem\u00a04.The set maximally refined observable, as the information for .Proof.\u00a0simultaneously. This combined measurement gives complete information about and\u00a0Let a consequence of the ability of the pointer states to persist while immersed in the environment. This resilience allows the information about the pointer observables to proliferate, very much in the spirit of the \u201csurvival of the fittest\u201d.Theorem 4 can be extended to nearly perfect records for assumptions satisfied by usual models of decoherence . The prnon trivial observable Note that the above Theorem does not guarantee the existence of a i\u00a0) An observer who probes only a fraction of the environment is able to find out the state of the system as if he measured ii\u00a0) Information about any other observable Two important consequences of this theorem follow: . As seen in redundantly in We can illustrate this preeminence of the pointer observable in our simple model: a single central spin Further confirmation and extension of the theorem quoted above is the relation betweenComparison of The origin of the consensus between different observers is the central lesson that follows from our considerations. In everyday situations, observers have no choice in the observables of systems of interest they will measure. This is because they rely on the \u201csecond hand\u201d information they obtain from the same environment that is responsible for decoherence. In addition, the environment that selects a certain pointer observable will record redundantly only the information about that observable.Information about complementary observables is in principle still \u201cout there\u201d, but one would have to intercept essentially all of the environment decoherence begets redundancy which; (ii) can continue to increase long after decoherence saturated entropy of the system at Our model is illustrated in Initially, pure decoherence is a reasonable approximation. However, as time goes on, correlations between spins of the environment gradually build up. Interactions between the spins of All of the models investigated so far were \u201cpure decoherence\u201d\u2014subsystems of the environment interacted only with the system The idealization of pure decoherence is often well-motivated. Photon environment, for example, consists of subsystems (photons) that interact with various systems of interest but do not interact with one another. There are, however, other environments\u2014such as air\u2014that contribute to or even dominate decoherence, but consist of interacting subsystems (air molecules). Thus, while the pointer basis is still untouched by decoherence, information about it will no longer be preserved in the individual subsystems of the environment\u2014it will become delocalized, and, hence, impossible to extract from the local fragments of the environment consisting of its natural subsystems.To investigate what happens when subsystems of The timescale over which pure decoherence is a good approximation depends on the strength of the couplings. In our case, the coupling between the system and the spins of the environment is significantly stronger than the couplings between the spins of Our simple model with weakly interacting environment subsystems illustrates why environments where the subsystems (photons) are in effect non-interacting are used by observers to gather information rather than environments (such as air) that may be more effective in causing decoherence but scramble information acquired in the process because their subsystems (air molecules) interact with each other.Evolution of a single harmonic oscillator (the system) coupled through its coordinate with a collection of many harmonic oscillators (the environment) is a well known exactly solvable model . This iHere, we summarize results . The the., 2004) approximf included in non-redundant information is dwarfed by the total amount of information available from even small fractions of Mutual information illustrated in partial information plots shows thCalculations simplify in the macroscopic limit where the mass of the system is large compared to masses of the environment oscillators. This regime allows for analytic treatment based on the Born-Oppenheimer approximation: Massive system follows its classical trajectory, largely unaffected by f of The basic observation is that the area of the ek, 2008 ; Roncaglek, 2008 ) is valif and so it is invariant under enlargement of In contrast to PIP\u2019s we have seen before , adding more oscillators to the environment does not simply extend the plateau: The shape of s-squeezed state decoheres to a mixed state with When the above equation for As trajectories decay, plateau flattens compared to what Equation (4.36) would predict. This will initially increase redundancy ence see . EventuaQuantum Brownian motion model confirms that decoherence leads to quantum Darwinism. However, details of quantum Darwinism in QBM setting are different from what we have becomes accustomed to in the models involving discrete Hilbert spaces of Buildup of redundancy still takes longer than the initial destruction of quantum coherence. Nevertheless, various time-dependent processes (such as the increase of redundancy caused by dissipation) remain to be investigated in detail. Moreover, localized states favored by einselection are redundantly recorded by f. Consequently, it is evident that We also note that surplus decoherence we have described before can be found in the case of QBM. This follows, in effect, from the fact that To sum up, we note that while broadly defined tenets of quantum Darwinism\u2014multiple records of Eventually the collection of oscillators begins to relax, and the information about the system flows from their individual states to correlations between them. This is because, even though the oscillators of the environment do not directly interact with each other, they do interact indirectly via the system oscillator: There is no perfect pointer observable for our harmonic oscillator The two decoherence models discussed above\u2014central spin model and quantum Brownian motion\u2014are the two standard workhorses of decoherence. They were the early focus of quantum Darwinism primarily because one could analyze them using many of the tools developed to study decoherence. We have thus seen quantum Darwinism in action, and we have already confirmed in these idealized models that the expectations about the shape of partial information plots resulting from decoherence and about the buildup of redundancy are satisfied\u2014with variations\u2014in both cases. This is reassuring. However, while redundancies appeared in both cases, they were modest scattering processes we turn to the model of decoherence discussed by Joos and Zeh (1985) that wasr\u2014that is initially in a non-local superposition (see In contrast to Joos and Zeh (1985) who focution see , althougThe scattering process is responsible for the decoherence of N photons results in the decoherence factor Scattering takes the initial pure state density matrix rate, is given by:I is the irradiance while To compute the decoherence factor \u0394x\u2192 see .allThe decoherence rate does not increase for arbitrarily large aturates ;(4.41)1f for several times. For large t identity What is even more important, redundancy continues to increase linearly with time at a rate given by the inverse of the decoherence time eh, 1985 .Redundancy of illuminated objects can quickly become enormous ,181. ForBy contrast with the case of the point source ), isotroRapid increase and large values of redundancy signify objectivity\u2014many (The flip side of the huge redundancies is irreversibility\u2014the difficulty of undoing redundant decoherence. Restoring the state of our (modest) ersatz Schr\u00f6dinger cat to the preexisting superposition would require control and manipulation all of the fragments of the environment. In our example this means de facto irreversible not just because observer in possession of the record of its outcome cannot reverse evolution that led to the wavepacket collapse and Jian., 2018) carried ., 2021) .The group of Fedor Jelezko used nitThe results of all of these experiments are consistent with what was expected, with one exception: If Decoherence has made it clear that quantum states are far more fragile than their classical counterparts. A state that is stable is selected\u2014einselected\u2014with the environment having decisive say in the matter. However, even this dramatic change of view turns out to underestimate the role of the environment.Quantum Darwinism demonstrates that preferred states are not only selected for their stability (ability to survive the \u201chostile environment\u201d) but are communicated by the very same environment that also serves as a communication channel. Therefore, the environment acts both as a censor (for some states) and as an advertising agent that disseminates many copies of the information about the pointer states while suppressing complementary information about their superpositions.Regarding the environment as a communication channel is more than a figure of speech: A quantum communication channel can be regarded called aDecoherence introduced the environment into the picture of quantum measurement. The original von Neumann\u2019s chain has fanned out: Parts of the chain separate from the links that connect Quantum Darwinism recognizes and quantifies this fanning out of the von Neumann chain. Shifty split could be placed anywhere along the plateau of the partial information plot. The information about We reviewed research aimed at understanding how the classical world we perceive emerges from the counterintuitive laws of quantum mechanics. It is time to take stock. Do we now understand why we perceive our undeniably quantum Universe as classical?quantum textbook axioms. The origin of Born\u2019s rule in the symmetries of entanglement matters in interpreting quantum probabilities, but\u2014as important as axiom (v) is for experimental predictions\u2014its derivation from the core quantum postulates (o)\u2013(iii) does not directly account for the familiar everyday reality.Quantum Darwinism holds the key to this last question. Deducing discreteness that sets the stage for the wavepacket collapse from repeatability and unitarity reveals quantum origin of quantum jumps, defines \u201cevents\u201d, and justifies the emphasis on the Hermitian nature of observables, but this is a derivation of one of the Quantum Darwinism, by contrast, explains why our world appears classical, and why XIX century physics (physics still relevant for our everyday routine) seemed at the time like the whole story. It shows how the information is channeled from the \u201cobjects of interest\u2019\u2019 to us, observers, leading to consensus about what exists\u2014to the idealization of objective classical reality.Our everyday world comprises \u201csystems of interest\u2019\u2019 endowed with the rest mass\u2014the focus of XIX century physics\u2014and environments that often play the role of communication channels. The quantumness of the massive \u201csystems of interest\u2019\u2019 is suppressed by decoherence that is continually uploading qmemes of their states into the environments that broadcast that information. Thus, every object of interest is ensconced in an expanding halo of qmemes\u2014information-carrying fragments of extanton (as in \u201cextant\u2019\u2019). Extantons are responsible for how we perceive our Universe. The tandem\u2014the macroscopic decohered system along with its information-laden halo\u2014fulfills Bell\u2019s desideratum for \u201cbeables\u2019\u2019 [The combination of the macroscopic, massive core with the information\u2014bearing halo defines an l, 1975) 18. As loExtantons exist as beables should: The state of the environment is of course perturbed by agent\u2019s measurements . However, redundancy means that this does not alter the information about the core still available from the rest of the halo in many redundant , not to mention planets or stars. Yet protons, mesons, atoms, molecules, planets, stars, etc., are all useful in representing and accounting for various phenomena in our Universe.Extantons account for the classical world of our everyday experience. Quantum Darwinism explains how they come about. We can reduce extantons to their constituents, but\u2014as other higher-level entities such as composite elementary particles, atoms, molecules, viruses, stars\u2014extantons enable an approximate, but simple and useful description of the classical realm, of the familiar world emerging from within the quantum substrate.Part of that simplification that led to the Newtonian view of the world is our habit of ignoring halos, carriers of the information, and focusing on the extanton cores. These cores are the \u201cobjects of interest\u2019\u2019. Many are subject to Newtonian dynamics. It was convenient to ignore the means by which the information about the cores is delivered, and just focus on the physics of the cores.Inseparable bond of the core with the halo is responsible for what we perceive. However, conditioned by Newtonian physics we tend to ignore the presence and the role of the halos, and just use the data they deliver to find out about the cores. In the end, only these cores count as elements of our everyday reality. Yet, it is the halos that bear responsibility for the suppression of quantum superpositions and for our perception of the familiar\u2014robust and objective\u2014classical world.The difficulty with the quantum-classical correspondence arises when the role of the halo is overlooked and the extanton core is treated as if it were isolated, and, therefore, subject to unitary evolution. Core is indeed quantum (as is everything else in our Universe) but it is by no means isolated. Therefore, one cannot expect the core of an extanton to follow a unitary quantum evolution. Nevertheless, whenever Newtonian dynamics is a good approximation)its classical evolution can be approximately reversible.No one has ever worried about interpretation of classical physics. This is because classical states were thought to be real\u2014to exist independently of what was known about them. There was no need to be concerned about the effect of information acquisition. Even though measurement could perturb a system, that perturbation could always be made as small as required.The main reason for the interpretational discomfort with quantum theory is our faith in the underlying objective reality. It is based on our everyday experience that leads us to believe the world we inhabit exists independently of the information we (or other agents) have.We owe this confidence in objective classical reality to the fact that we are immersed in the extanton halos and inundated with the information about their cores. As a result of this overload with \u201cfree\u201d data we have grown up believing that we can examine systems and determine their states without perturbing them\u2014classical measurement would just update the record (change the state of the apparatus or of the observer\u2019s memory) without \u2018backreaction\u2019. In the classical setting information about a system is obtained, but its state or its evolution is untouched.myth of immaculate perception. It asserts a unidirectional information flow that reveals the state of the system but leaves it unaffected. This seems to defy the spirit of Newton\u2019s principle that action elicits reaction.One might call this a Quantum Darwinism accounts for the origin of this myth. All macroscopic objects telegraph their pointer states via their decohering environments. They are enveloped by information halos\u2014by the environment with multiple records of their decoherence-resistant states. Our everyday world does not consist of isolated systems. Rather it is defined by the extantons consisting of a macroscopic object enveloped in and heralded by its halo, imprinted on the environment.There is a great variety of extantons. They all consist of the core and the halo that \u201cknows\u2019\u2019 the state of the core, and may be persuaded to share that information with observers. Planets are extanton cores and so are the grains of photographic emulsion. Any object one can see is likely an extanton core, its state communicated to us by photons\u2014by its photohalo. Some extantons (like planets) follow approximately reversible dynamics. Others (like grains of photographic emulsion or Brownian particles) are heavily damped or embedded in an immobilizing medium competing with the photohalo in monitoring of the core . Every apparatus pointer is an extanton core.Observers intercept fractions of the halo to gain information about the core. Direct measurement of the core is in principle also possible, but only measurements of the pointer observable would lead to predictable results: Other outcomes\u2014superpositions of pointer states\u2014are quickly invalidated by decoherence. Thus, except for laboratory settings (where decoherence can be kept at bay by a near-perfect isolation) the only observables with predictive value are the pointer observables readily available from the halo.Photohalo is the main channel through which observers find out the state of the core. The information available from the photohalo is usually limited to the data that are in effect macroscopic .Photons play a preeminent role as information carriers. Every object we know is bathed in a radiation environment. Each is surrounded by an information halo, its photons disseminating qmemes with the speed of light. We eavesdrop on these photohalos, intercepting small fractions that nevertheless reveal the state of the core.Photoextantons are the family of extantons that advertise the state of their core via their photohalos. One can consider extantons where photohalo is the only relevant environment. There are at least two good reasons for this. To begin with, our eyesight is responsible for most of the information we obtain, so it is of interest to consider photoextantons. Perhaps more importantly, there is a sense in which photoextantons come close to the ideal\u2014one might say Platonic ideal\u2014of the separation of existence and information detached from existence.Information has\u2014apart from the dramatic consequences of decoherence\u2014only a negligible effect on the evolution of the cores. Photohalo detaches from the core and runs off seemingly without any dynamical consequences while the core can evolve in approximate accord with Newton\u2019s laws. Questions such as \u201cDoes the moon exist when no one\u2019s looking?\u2019\u2019 are motivated by the illusion that one can apply quantum theory to the isolated cores of extantons and recover classical reality.epiontic. Quantum physics has eliminated separation of existence and information. Nevertheless, extanton structure restores this separation (with suitable caveats): The core exists (it persists in a pointer state). And the information about it is continually detached and propagates as the photohalo.Quantum states are Everyday practice of quantum theory has inherited from classical physics the habit of dealing with isolated systems. Yet, we can never encounter isolated macroscopic extanton cores. Trying to understand cores of extantons as if they were isolated is the cause of the \u201cmeasurement problem\u2019\u2019. Decoherence and einselection were the first steps towards its resolution, towards the understanding why our Universe looks classical to us. Quantum Darwinism provides the complete answer, and extantons are its embodiment.Properties of systems that reside in the extanton cores and give rise to the qmemes in reversible dynamics of classical systems. Trajectories in phase space were unaffected by the information transfer. In particular, classical dynamics involved in the measurement process could be reversed even when the outcome of the measurement was recorded. By contrast noticeable influence on trajectories of the pointer states of the core. However, cores can interact indirectly with other cores or scatter elastically or inelastically. Consequences of such interactions on the motion or the state of the core or on its properties will be reflected in the photohalo.When core is sufficiently massive, emission or scattering of photons has negligible effect on its momentum . How heavy the core should be to make such an approximation accurate depends on the energy of the emitted or scattered photons. Planets are clearly sufficiently massive, and so are billiard balls or even dust grains ,23,174. Irreversibility associated with the wavepacket collapse is a natural consequence of the photohalo. As soon as a minute fraction of the photohalo escapes, the \u2018reduction of the state vector\u2019 becomes irreversible, since the escaped photons are gone for good, And, as we have seen in The information about the classical states (of the cores) becomes detached: Separation of the states of the cores from the information about them is how extantons account for the emergence of the objective classical reality. This mechanism is also the uniquely quantum origin of irreversibility in our Universe.Photohalo may not be the only environment. However, in our Universe interactions depend on distances. Therefore, localized pointer states imprinted on the photohalo are left intact also by the other environments that may be contributing to decoherence but\u2014like air\u2014are not as useful as witnesses.objective existence was established operationally\u2014they could be found out by an initially ignorant observer without getting perturbed in the measurement process. Hence, they existed independently of what was known about them.States in classical physics were \u201creal\u201d: Their Information was, by contrast, \u201cnot real\u201d. This was suggested by the immunity of classical states to measurements, and by the fact that, in Newtonian dynamics, information about an evolving system was of no consequence for its evolution. Information was what the observer knew subjectively, a mere shadow of the real state, irrelevant for physics.This dismissive view of information ran into problems when the classical Universe of Newton confronted thermodynamics. Clash of these two paradigms led to Maxwell\u2019s demon, and is echoed in the discussions of the origins of the arrow of time.The specter of information was and still is haunting physics. The seemingly unphysical record state was beginning to play a role reserved for the real state!Quantum states are epiontic. They combine information and existence and (like photons or electrons that can be wave-like or particle-like) they can reveal one or the other aspect of their nature depending on circumstances.We have just seen how, in the quantum setting, in extantons, existence and information about existence intertwine. The state known to observers is defined and made objective by what is known about it\u2014by the information observers can access. \u201cIt from bit\u201d comes to mind .The main new ingredient is the dramatic upgrade of the role of the environment. It has information\u2014multiple records of information is physical [there is no information without representation\u2014information must reside somewhere . And the presence and availability of such evidence (objective because there are plenty of records of the pointer state) has its legal consequences.In classical Newtonian settings information might have been dismissed as unphysical as it had no significance for dynamics. But r, 1991) . MoreoveThe role of Moreover, testimony offered by the environment is biased\u2014it depends on how (through what observable) Operational criterion for objective existence is the ability to find out a state without disturbing it. According to this operational definition, pointer states exist in more or less the same way their classical counterparts did: They can be found out without getting perturbed by anyone who examines one of the multiple copies of the record of existential interpretation. Its essence is the operational definition of objective existence of physical states: To exist, a state must, at the very least, persist or evolve predictably in spite of the immersion of the system in its environment. Predictability is the key to einselection, but persistence is only a necessary condition.In search for the relation between quantum formalism and the real world we have weaved together several ideas that are very quantum to arrive at the Objective existence requires more: It should be possible to find out a state without perturbing it\u2014without threatening its existence. When that last desideratum is met, many observers will be able to reach consensus, a well\u2014motivated practical criterion of objective existence.preferred pointer states. This is a new insight into the quantum origin of quantum discreteness. Predictability is the \u201croot cause\u201d of the wavepacket collapse and quantum jumps. It also justifies Hermitian nature of quantum observables and explains breaking of the unitary symmetry, the crux of the collapse axiom (iv).Let us briefly recapitulate how objective existence arises in the quantum setting: We started with axioms (i) and (ii) that sum up mathematics of quantum theory: They impose the quantum principle of superposition, and demand unitarity, but make no connection with the \u201creal world\u201d. Addition of predictability (via the repeatability postulate (iii), the only uncontroversial measurement axiom), and recognition that our Universe consists of systems (axiom (o)) leads to the origin of probabilities and Born\u2019s rule, axiom (v). We have done this without appealing to decoherence (as this would have courted circularity in the derivation). Nevertheless, decoherence\u2014inspired view is reflected in the envariant approach: To assign probabilities to pointer states we first had to show how to get decoherence without using tools of decoherence such as reduced density matrices and demonstrate that relative phases between outcomes do not matter.Our next task was to understand Envariance provides the answer, but\u2014strictly speaking\u2014only for Schmidt states. We take this to mean that usual rules of the probability calculus will strictly hold for pointer states only after their superposition has been thoroughly decohered. Pointer states\u2014Schmidt states coincidence is expected to be very good indeed: Probabilities one has in mind ultimately refer to pointer states of measuring or recording devices. These are usually macroscopic, so their interaction with the environment will quickly align Schmidt basis with pointer states. Born\u2019s rule follows.Probabilities derived from envariance are objective: They reflect an objective\u2014and experimentally testable\u2014symmetry of the global state ,25: WhenExistential interpretation of quantum theory assigns \u201crelatively objective existence\u201d ,7,36,198Existential interpretation is obviously consistent with the relative states interpretation: Redundancy of the records disseminated throughout the environment suggests a natural definition of branches that are classical in the sense that an observer can find out a branch with indirect measurements and stay on it, rather than \u201ccut off the branch he is sitting on\u201d with a direct measurement. This is more than einselection, and much more than decoherence, although the key ingredient\u2014environment\u2014is still key, and the key criterion is \u201csurvival of the fittest\u201d\u2014 immunity of the pointer states to monitoring by The role of Extantons combine the source of information (extanton core) with the means of its transmission . Extanton is an extant composite entity with the object of interest in its core that is decohering and imprinting qmemes on the information-laden halo, part of the environment that pointer states of the core. Information about them is disseminated by the halos throughout the Universe.Photohalos are especially efficient in such \u201cadvertising\u201d. Fragments of the halo intercepted by the observers inform them about the state of its core. Extanton cores persist as classical states would\u2014independent of what is known about them. While they are not fundamental, they are fundamentally important for our perception of the quantum Universe we inhabit as a classical world. Extantons fulfill John Bell\u2019s desiderata for \u201cbeables\u201d.Decoherence affects record keeping and information processing hardware of observers. Therefore, it is relevant for our consciousness, as agents\u2019 consciousness presumably reflects states and processes of their neural networks. As was already noted some time ago by Tegmark (2000) , individIt is a separate and intriguing question whether a robot equipped with a quantum computer could \u201cdo better\u201d and perceive quantumness we are bound to miss. We note, however, that the relevance of this question for the subject at hand\u2014i.e., why does our quantum Universe appear to us as a classical world devoid of quantum weirdness\u2014is at best marginal. After all, as already noted, rapid decoherence in the neural networks of our brains precludes quantum information processing.Moreover, if such a robot relied (as we do) on the fragments of the environment for the information about the system of interest, it could access only the same information we can access. This information is redundant\u2014hence, classical \u2014and quaExistential interpretation\u2014as defined originally \u2014relied Decoherence, one might say, \u201cstrikes twice\u201d: It selects preferred states of the systems, thus defining what can persist, hence, exist. It also limits correlations that can persist, so that the observer\u2019s memory or the apparatus pointer will only preserve correlations with the einselected states of the measured system when they are recorded in the einselected memory states.This is really the already familiar discussion of the quantum measurement problem with one additional twist: Not just the apparatus, but also the systems of everyday interest to observers are subject of decoherence. Thus, the post-measurement correlations (when investigated using discord) must now be \u201cclassical-classical\u201d using terminology of Piani, Horodecki, Horodecki, 2008 , while iQuantum Darwinism has a Darwinian name, but how Darwinian is it really? This is a vague question about nomenclature, and we shall pass it by. A related and more pointed question is: Does quantum Darwinism have any significance for the evolution of living organisms and for their survival? There are then two even more focused questions one can pose: Are the processes of imprinting information and passing it on relevant for natural evolution? Moreover, do living organisms take advantage of the proliferation of information about pointer states?We note at the outset that natural selection and Darwinian evolution require multiple redundant records . Redundant records imply preservation of information and its propagation. DNA is disseminated by various means, but DNA molecules are thoroughly decohered carriers of information about an even more decohered parent organism.The goals and the nature of natural evolution are somewhat different but the transfer of actionable information are no longer needed. Nevertheless, there is the next generation of records\u2014in the apparatus, in the retina, or in the brain of the observer. Such information repositories inherit the memes\u2014the essence of the information detected by the senses.That leads to further consequences: Agents (living organisms) react to data. Their actions depend on what they have perceived. In the evolutionary context such actions are taken to optimize their chances of survival. Hence, evolutionary success in the original Darwinian sense depends on the ability to acquire and process information about extantons that is obtained through quantum Darwinian processes that starts with decoherence and proliferation of qmemes.Redundancy facilitates accessibility and explains the objective nature of events, and, hence, emergence of the objective classical reality. Consequences of such events influence multiple generations of their records and have implications for their recipients: After all, actions taken by the living organisms are based on perceptions\u2014on what was recorded. Knowledge of events that take place is essential for survival. This is feedback. It does not necessarily require conscious decisions , but it allows, and indeed, calls for, adaptation. Feedback is also what allows for learning from experience. Thus, while natural selection and Darwinism can be analyzed without any reference to quantum goings on, it does involve steps that depend on decoherence and proliferation of information.Our senses did not evolve to test and verify quantum theory. Rather, they evolved through natural selection where survival of the fittest played a decisive role. When there is nothing to be gained from prediction, there is no evolutionary reason for perception. Only classical states that pass through the predictability sieve and deposit redundant easily accessible records in their environment are robust and easy to access.Quantum Darwinian requirement of redundancy appears to be built into our senses, and, in particular, into our eyesight: The wiring of the nerves that pass on the signals from the rods in the eye\u2014cells that detect light when illumination is marginal, and that appear sensitive to individual photons \u2014tends toThis makes evolutionary sense\u2014rods can misfire, so such built-in veto threshold suppresses false alarms. Frogs and toads have apparently lower veto thresholds, possibly because they are cold-blooded, so they may not need to contend with as much noise, as thermal excitation of rods appears to be the main source of \u201cfalse positives\u201d.Quantum Darwinism relies on repeatability. As observers perceive outcomes of measurements indirectly\u2014e.g., by looking at the pointer of the apparatus or at the photographic plate that was used in a double-slit experiment\u2014they will depend, for their perceptions, on redundant copies of photons that are scattered from (or absorbed by) the apparatus pointer or the blackened grains of photographic emulsion. Thus, repeatability is not just a convenient assumption of a theorist: This hallmark of quantum Darwinism is built into our senses. And\u2014as we have seen in What we are conscious of is then based on redundant evidence. Quantum Darwinist update to the existential interpretation is to demand that states exist providing that one can acquire redundant evidence about them indirectly, from the environment. This of course presumes stability in spite of decoherence but This paper has largely avoided issues of interpretation, focusing instead on consequences of quantum theory that are \u201cinterpretation independent\u201d, but may constrain interpretational options. We have been led by quantum formalism to our conclusions, but they are largely beyond interpretational disputes. Our \u201cexistential interpretation\u201d is in that sense not an interpretation\u2014it simply points out the consequences of quantum formalism and some additional rudimentary assumptions. It recognizes that quantum states are epiontic: Like photons or electrons that can act as waves or particles, quantum states can exhibit epistemic or ontic side of their nature, depending on circumstances. In contrast to Bohr (who regarded them as purely epistemic) of Everett they can perform either as robust elements of reality or as information carriers. These two roles are complementary: both are essential for extantons.(1) The conceptual scheme of \u201crelative state\u201d quantum mechanics is completely different from the conceptual scheme of the conventional \u201cexternal observation\u201d form of quantum mechanics and (2) The conclusions from the new treatment correspond completely in familiar cases to the conclusions from the usual analysis\u201d.It is nevertheless useful to see how the two best known interpretations of quantum theory\u2014Bohr\u2019s \u201cCopenhagen Interpretation\u201d (CI) and Everett\u2019s \u201cRelative State Interpretation\u201d (RSI) fit within the constraints that we have derived above by acknowledging the paramount role of the environment. To anticipate the conclusion, we quote John Archibald Wheeler (1957) , who\u2014comBohr insisted on preexistence of the classical domain of the Universe to render outcomes of quantum measurements firm and objective. Quantum Darwinism accomplishes that goal: Decoherence takes away quantumness of the system, but a system that is not quantum need not be immediately classical: Objective nature of events and, above all, of extantons arises as a result of redundancy. Consensus about what happened and what exists is reached only in presence of large redundancy. Large redundancy yields a very good approximation of \u201cthe classical\u201d, like finite many-body systems that have a critical point marking a phase transition which is, strictly speaking, precisely defined only in the infinite size limit. Indeed, Quantum Darwinism might be regarded as a purely quantum implementation of the \u201cirreversible act of amplification\u201d that was such an important element of CI.Physical significance of a quantum state in CI was purely epistemic is attained only in the limit of large redundancy. It is clear why this is a good approximation in the case of macroscopic systems. However, it is also clear that there are intermediate stages on the way from quantum to classical, and that a system can be no longer quantum but be still far away from classical objective existence.There are two key ideas in Everett\u2019s writings. The first one is to let quantum theory dictate its own interpretation. We took this \u201clet quantum be quantum\u201d point very seriously. The second message (that often dominates in popular accounts) is the Many Worlds mythology. In contrast \u201clet quantum be quantum\u201d it is less clear what it means, so\u2014in the opinion of this author\u2014there is less reason to take it at face value.objective derivation of probabilities not just in the quantum setting, but also in the history of the concept of probability.It is encouraging for the relative states point of view that the long - standing problem of the origin of probabilities has an elegant solution that is very much \u201crelative state\u201d in the spirit. We have relied on symmetries of entangled states. This allowed us to derive objective probabilities for individual events. We note that this is the first such Envariant derivation of Born\u2019s rule is based on entanglement (which is at the heart of the relative states approach). We have not followed either proposals that appeal directly to invariant measures on the Hilbert space ,11, or aThe emergence of the classical world from within our quantum Universe is a difficult problem. The traditional expectation\u2014that it will be somehow resolved by a single new idea\u2014did not pan out. Rather, several interdependent new insights were needed to account for quantum jumps, for the appearance of the collapse, for the preferred pointer states, for probabilities, and for the perception of the objective reality\u2014for all the familiar ingredients of \u2018the classical\u2019.Our strategy was to avoid purely interpretational issues and to focus instead on technical questions. They can often be answered in a definitive manner. In this way, we have gained new insights into selection of preferred pointer states that go beyond decoherence, found out how probabilities arise from entanglement, and discovered how objectivity follows from redundancy.All of that fits well with the relative states point of view and with a similar although less Everettian approach of, e.g., Rovelli . There aThe first point concerns the nature of quantum states, and its implications for the interpretation. One might regard states as purely epistemic (as did Bohr) or attribute to them \u201cexistence\u201d. Technical results described above suggest that truth lies somewhere between these two extremes, and these two aspects are complementary in the sense of Bohr. It is therefore doubtful whether one is forced to attribute \u201creality\u201d to all of the branches of the universal state vector. Indeed, such a view combines a very quantum idea of a state in the Hilbert space with a very classical literal ontic interpretation of that concept.These two views of the universal state vector are incompatible. As we have emphasized, an unknown quantum state cannot be found out. It can acquire objective existence only by \u201cadvertising itself\u201d in the environmentThe insistence on the absolute existence of the universal state vector as an indispensable prerequisite in interpreting quantum theory brings to mind the insistence on the absolute time and space. They seemed indispensable since Newton, yet both became relative and observer-dependent in special relativity. The absolute universal state vector may be\u2014like the Newtonian absolute space and time, or for that matter, like isolated systems of classical physics\u2014an idealization that is untenable in the quantum realm.As noted in Objective existence can be acquired (via quantum Darwinism) only by a relatively small fraction of all degrees of freedom within the quantum Universe: The rest is needed to \u201ckeep records\u201d. Extantons are a good illustration. Clearly, there is only a limited (if large) memory space available for this at any time. This limitation on the total memory available means that not all quantum states that exist or quantum events that happen now \u201creally happen\u201d in the sense of the existential interpretation: Only a small fraction of what occurs will be still available from the records in the future. So the finite memory capacity of the Universe implies indefiniteness of the present and impermanence of the past.To sum it up, one can extend John Wheeler\u2019s dictum \u201cthe past exists only insofar as it is recorded in the present\u201d. This is one of the topics that could have been discussed in this review, but was not. Fortunately, Ref. providesConsensus can be reached about objective histories, a more selective set than histories that are just consistent. This may help settle the so-called class selection problem\u2014that is, selecting candidates for physically relevant histories from among the set of all consistent histories\u2014which is one of the central unresolved issues of the consistent histories interpretation of quantum physics . Fortunately, there are papers by Horodecki, Korbicz, and Horodecki (2015) , Le and c-maybe model [Some of the quantum information theoretic tools used to implement criteria for objective existence have also been \u2018beyond the scope\u2019. In particular, quantum Chernoff bound has been successfully used in models , and we be model ).These results confirm that there is no need for a unique best quantum information-theoretic tool to study quantum Darwinism. We have already seen that Shannon and von Neumann mutual entropy, and various half-way quantities including Holevo In presence of sufficiently large redundancy the precise number of records in the environment does not matter: As long as redundancy is large, emergence of the consensus\u2014hence, objective classical reality\u2014will be confirmed by perceptions of observers.All of our conclusions followed from the core quantum postulates (o)\u2013(iii) and the insight that quantum states are epiontic. These two aspects of their nature are complementary (like the wave and particle traits of photons and electrons). They both play a role in the emergence of objective classical reality with information and existence seemingly separated \u2013 the state of affairs we are accustomed to in our everyday experience.In the field known for divergent views and lively discussions it is too early to expect consensus on which of the mysteries of the quantum-classical correspondence have been explained, but deducing inevitability of the discreteness and of quantum jumps, a simple and physically transparent derivation of Born\u2019s rule, and\u2014above all\u2014accounting for the emergence of objective existence from the fragile quantum states mark a significant progress. Moreover, there are no obvious obstacles in pursuing the program outlined here to provide an even fuller account of the interrelation of the epistemic and ontic aspects of quantum states, or to incorporate evolving quantum states\u2014thus exploring emergence of objective histories\u2014within the framework of quantum Darwinism."} +{"text": "In the original publication title , we refeDr. Jillian J. Haszard was not included as an author in the original publication. J.J.H. joined the team after the original publication to lead the statistical reanalysis. Thus, we have added authorship in the corrected paper. New Authorship:1,*, Benjamin D. Fletcher 1, Jillian J. Haszard 2, Juliet M. Pullar 2, Emma Spencer 3, Louise A. Mainvil 4 and Margreet C. M. Vissers 2Tamlin S. Conner New Authorship Statement:Author Contributions: Conceptualization, T.S.C. and M.C.M.V.; methodology, T.S.C. and M.C.M.V.; statistical analyses, J.J.H., T.S.C., B.D.F., and M.C.M.V.; investigation, T.S.C., B.D.F., J.M.P., and E.S.; resources, T.S.C., L.A.M., and M.C.M.V.; writing\u2014original draft preparation, T.S.C., B.D.F., and M.C.M.V.; writing\u2014review and editing, T.S.C., B.D.F., J.M.P., and M.C.M.V.; visualization, J.J.H. and M.C.M.V.; supervision, T.S.C. and M.C.M.V.; funding acquisition, T.S.C. and M.C.M.V. All authors have read and agreed to the published version of the manuscript.p-values. In the original publication, the statistical analyses did not take into account possible dependency in randomisation groupings. Therefore, analyses were re-run using mixed- effects modelling with two randomization clusters as random effects to account for any correlated errors. The corrected results are presented in the Abstract, Corrected Abstract: Abstract: Consumption of vitamin C-rich fruits and vegetables has been associated with greater feelings of vitality. However, these associations have rarely been tested in experimental trials. The aim of the current study was to test the effects of eating a vitamin C-rich food (kiwifruit) on subjective vitality and whether effects are driven by vitamin C. Young adults with plasma vitamin C < 40 \u00b5mol/L were allocated to three intervention conditions: kiwifruit (2 SunGold\u2122 kiwifruit/day), vitamin C (250 mg tablet/day), placebo (1 tablet/day). The trial consisted of a two-week lead-in, four-week intervention, and two-week washout. Plasma vitamin C and vitality questionnaires were measured fortnightly. Self-reported sleep quality and physical activity were measured every second day through smartphone surveys. Nutritional confounds were assessed using a three-day food diary during each study phase. Plasma vitamin C reached saturation levels within two weeks for the kiwifruit and vitamin C groups. Participants consuming kiwifruit showed a trend of improvement in mood disturbance, significantly decreased fatigue, and significantly improved well-being after two weeks of the intervention. Improvements in well-being remained elevated through washout. Consumption of vitamin C tablets alone was associated with improved well-being after two weeks, and additionally improved mood and fatigue for participants with consistently low vitamin C levels during lead-in. Diet records showed that participants consuming kiwifruit reduced their fat intake during the intervention period. Intervention effects remained significant when adjusting for condition allocation groupings, age, and ethnicity, and were not explained by sleep quality, physical activity, BMI, or other dietary patterns, including fat intake. There were no changes in plasma vitamin C status or vitality in the placebo group. Whole-food consumption of kiwifruit was associated with improved subjective vitality in adults with low vitamin C status. Similar, but not identical changes were found for vitamin C tablets, suggesting that additional properties of kiwifruit may contribute to improved vitality.Corrected In the original publication, The original publication lacked detail in the randomization procedure and did not clarify that there was non-random allocation in the study implementation. This stemmed from allocating the first two weeks of participants to the kiwifruit condition due to circumstances outside our control . The correct information appears below and in Section 2.3 of the corrected manuscript. We have also included Supplementary Figure S1 to reflect the full condition allocation schedule.2.3. Condition AllocationOur intention was to avoid participants being exposed to the other conditions during allocation of the intervention . This was achieved by group randomisation based on scheduled clinic, either on separate days or across days, to ensure that everyone attending the same clinic would receive either kiwifruit or tablets. Participants receiving tablets at a given clinic were typically a random mix of the active and placebo groups. The allocation of clinics was determined by the lead author using a random number generator. As allocation occurred after participants were already enrolled into their clinic day , the clinical study co-ordinator and prospective participants were unaware of their allocation when booking clinic appointments and did not learn of their allocation until they attended the clinic. A delay in the delivery of tablets meant that clinics in the first and second weeks were non-randomly allocated to the kiwifruit condition, and those in the third and fourth weeks, to the tablet conditions (randomised to placebo or vitamin C), with the remaining clinics randomised as intended. A randomisation schedule is shown in Supplementary Figure S1. Randomisation groups were accounted for in the statistical analyses . Tablets were bottled and labelled by the lead author (TSC) with the label including only the participant\u2019s first and last name and tablet instructions to \u201cchew one tablet daily, store in a dark dry place, and return bottle and unused tablets on next visit\u201d. All research assistants and participants were double- blinded to their tablet condition. It was not possible to blind research assistants or participants to the kiwifruit condition. The separation of allocation clinics, however, meant that these participants were unaware of the nature of the other treatment conditions. Condition information was kept in an electronic password-protected document by the lead author (TSC) and unblinded following data collection and entry.The authors apologize for any inconvenience caused and state that the primary scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "The initials of the third and sixth authors are indexed incorrectly in PubMed. The correct initials are, respectively: Galli Robertson A; McCartney Waggle J.https://doi.org/10.1371/journal.pone.0203463The correct citation is: Jasny L, Dewey AM, Galli Robertson A, Yagatich W, Dubin AH, McCartney Waggle J, et al. (2018) Shifting echo chambers in US climate policy networks. PLoS ONE 13(9): e0203463. http://www.drfisher.umd.edu/CCP.html.Additionally, the Data Availability statement for this paper is incorrect. The correct statement is: Data are available from the Climate Constituencies study at The publisher apologizes for the errors."} +{"text": "Chem. Chem. Phys., 2022, 24, 9403\u20139410, https://doi.org/10.1039/D2CP00686C.Correction for \u2018Modeling the heating and cooling of a chromophore after photoexcitation\u2019 by Elizete Ventura The published version of this article contained errors in part of the funding information in the Acknowledgements. The corrected funding information for M. T. do C., J. M. T. and M. B. is as follows: M. T. do C., J. M. T. and M. B. have received funding from the European Union\u2019s Horizon 2020 research and innovation programme under the grant agreement no. 828753.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Trujillonella and Trujillonella endophytica, Pleomorpha and Pleomorpha daqingensis, Goekera and Goekera deserti and Blastococcus xantinilythicus.In the published article, there were some nomenclatural errors in the protologues of Final remarks and taxonomic consequences, as follows:A correction has been made to the section Description ofTrujillonellagen. nov.Trujillonella named in honour of Martha E. Trujillo in recognition of her contributions to microbial systematics, mainly on Actinobacteria, on Bergey's Manual trust, and as the Editor-in-chief of the International Journal of Systematic and Evolutionary Microbiology.Tru.jil.lo.nel'la. N.L. fem. dim. n. meso-diaminopimelic acid. The predominant menaquinone is MK-9(H4), with MK-8 and MK-9(H6) as minor components. The basic polar lipid profile contains diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. The major fatty acids are iso-C16:0, iso-C15:0 and C18:1\u03c99c. The basic whole-cell sugar pattern includes arabinose and galactose. The genomic G + C content is 71\u201372%. The type species of Trujillonella is Trujillonella endophytica comb. nov.Cells are aerobic, non-motile, non-spore-forming, Gram-stain positive, catalase-positive and oxidase-negative. Cells occur singly, in pairs or in tetrads, often tending to form aggregates. The peptidoglycan in the cell-wall contains Description ofTrujillonella endophyticacomb. nov.T. en.do.phy'ti.ca .Blastococcus endophyticus Zhu et al. 2013 emend. Hezbri et al. 2016.Basonym: The properties are as given in the species description by Zhu et al. and emenT is FOEE00000000.The accession number for the whole genome sequence of strain DSM 45413T = CCTCC AA 209045T = DSM 45413T = KCTC 19998T was isolated from healthy leaves of Camptotheca acuminata collected in Yunnan Province, south-west China.The type strain YIM 68236Description ofPleomorphagen. nov.pleon more; Gr. fem. n. morphe, shape or form; N.L. fem. n. Pleomorpha, organism showing multiple forms.Ple.o.mor'pha. Gr. adv. meso-diaminopimelic acid. The predominant menaquinone is MK-9(H4). The basic polar lipid profile contains diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol. The major fatty acids are iso-C16:0 and iso-C15:0. The basic whole-cell sugar pattern includes galactose, glucose and xylose. The genomic G + C content is 73\u201374%. The type species of Pleomorpha is Pleomorpha daqingensis comb. nov.Pleiomorphic, motile, spore-forming, aerobic, Gram-stain positive cells. Those occurs singly or associated in aggregates. The peptidoglycan in the cellwall contains Description ofPleomorpha daqingensiscomb. nov.P. da.qing.en'sis .Geodermatophilus daqingensis Wang et al. 2017.Basonym: The properties are as given in the species description by Wang et al. with theT is JACBZT000000000.The accession number for the whole genome sequence of strain DSM 104001T = CGMCC 4.7381T = DSM 104001T was isolated from petroleum- contaminated soil in Daqing city, China.The type strain WT-2-1Description ofGoekeragen. nov.Goekera, named in honour of Markus G\u00f6ker in recognition of his contributions to microbial systematics, including work on Actinobacteria, on the List of Prokaryotic Names with Standing in Nomenclature (LPSN), and as a member of the Judicial Commission.Goe'ke.ra. N.L. fem. n. meso-diaminopimelic acid. The predominant menaquinone is MK-9(H4), with MK-8(H4) as a minor component. The basic polar lipid profile contains diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylmethylethanolamine and phosphatidylinositol mannoside. The major fatty acids are C18:1\u03c99c, iso-C16:0, C16:0, iso-C15:0, and C16:1\u03c97c.The basic whole-cell sugar pattern includes arabinose, glucose and ribose. The genomic G + C content is 74\u201375%. The type species of Goekera is Goekera deserti comb. nov.Cells are motile, non-spore-forming, aerobic, Gram-stain positive, catalase and oxidase positive cocci and/short rods. Bud-like structure was observed for some cells. The peptidoglycan in the cell-wall contains Description ofGoekera deserticomb. nov.G. de.ser'ti .Modestobacter deserti Jiang et al. 2023.Basonym: The properties are as given in the species description by Jiang et al. with theT is JAAGWK000000000.The accession number for the whole genome sequence of strain CPCC 205119T = I12A-02624T = KCTC 49201T = NBRC 113528T was isolated from moss-dominated soil crusts collected from Shapotou NDER in Tengger Desert, China.The type strain CPCC 205119Emended description ofBlastococcus xanthinilyticusHezbri et al. (2018)The properties are as given in the species description by Hezbri et al. with theT is VNHW00000000.The accession number for the whole genome sequence of the type strain DSM 46842T = DSM 46842T = CECT 8884T was isolated from a marble sample collected from the Bulla Regia monument, Northern Tunisia.The type strain BMG 862The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way."} +{"text": "K. Jesudoss RSC Advances article due to concerns with the reliability of the data.The Royal Society of Chemistry, with the agreement of the authors, hereby wholly retracts this In Fig. 2 the data for (a), (b) and (c) contains sections of identical noise.In Fig. 7 there are several instances of overlapping images. Fig. 7a and e are identical, Fig. 7b and f have partial overlap, and Fig. 7c and d have partial overlap.Given the significance of these concerns, the findings presented in this paper are no longer reliable.Signed: S. K. Jesudoss, J. Judith Vijaya, K. Kaviyarasu, L. John Kennedy, R. Jothi Ramalingam, Hamad A. Al-Lohedanth August 2022.Date: 18RSC Advances.Retraction endorsed by Laura Fisher, Executive Editor,"} +{"text": "Arachis hypogaea), a progeny of the cross between A. duranensis and A. ipaensis, is an important oil and protein crop from South America. To date, at least six Arachis genomes have been sequenced. WRKY transcription factors (TFs) play crucial roles in plant growth, development, and response to abiotic and biotic stresses. WRKY TFs have been identified in A. duranensis, A. ipaensis, and A. hypogaea cv. Tifrunner; however, variations in their number and evolutionary patterns across various Arachis spp. remain unclear.Cultivated peanut Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner. The results showed that the WRKY TFs underwent dynamic equilibrium between diploid and tetraploid peanut species, characterized by the loss of old WRKY TFs and retention of the new ones. Notably, cultivated peanuts inherited more conserved WRKY orthologs from wild tetraploid peanuts than their wild diploid donors. Analysis of the W-box elements and protein\u2013protein interactions revealed that different domestication processes affected WRKY evolution across cultivated peanut varieties. WRKY TFs of A. hypogaea cv. Fuhuasheng and Shitouqi exhibited a similar domestication process, while those of cv. Tifrunner of the same species underwent a different domestication process based on protein\u2013protein interaction analysis.WRKY TFs were identified and compared across different Arachis spp.This study provides new insights into the evolution of WRKY TFs in The online version contains supplementary material available at 10.1186/s12864-023-09149-z. These2) motif , 2, whilr motif) , 2. Grour motif) , 2, of wr motif) , 2, 5.Arachis duranensis, Arachis ipaensis, Cajanus cajan, Cicer arietinum, Glycine max, Lotus japonicas, Lupinus angustifolius, Medicago truncatula, Phaseolus vulgaris, Trifolium pratense, Vigna angularis, and Vigna radiate [G. max, A. duranensis, and A. ipaensis [Several WRKY TFs have been identified in diverse plant species at the genome level , 7. Nota radiate . The WRK radiate . Duplica radiate . Syntenyipaensis , 9. Moreipaensis , 8.Arachis hypogaea) is an important oil and protein crop from South America [A. duranensis and A. ipaensis [A. monticola is a wild allotetraploid plant known to be the direct progenitor of A. hypogaea [Arachis species has been completed, including A. duranensis, A. ipaensis, A. monticola, A. hypogaea cv. Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner [Arachis species provides crucial data for evolutionary studies at the genome level. In A. duranensis, duplicated gene pairs have different responses to drought and nematode stress, and old and young duplicate genes have divergent functions [A. duranensis and A. ipaensis, gradual selection and purifying pressure act on the somatic tissue-specific and sex-specific genes [A. hypogaea except in reproductive tissues [Arabidopsis [Cultivated peanut , LRR-containing genes, and heat shock transcription factor (HSF) [Arachis genomes [A. monticola, A. hypogaea cv. Fuhuasheng, and A. hypogaea cv. Shitouqi compared to A. duranensis and A. ipaensis [In addition to genome-level analysis, gene family identification has also been used to study or (HSF) \u201326. To o genomes . The stuipaensis .A. duranensis, A. ipaensis, and A. hypogaea cv. Tifrunner [A. hypogaea cv. Tifrunner genome [A. monticola, A. hypogaea cv. Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner. We compared the number of WRKY TFs across the various Arachis species to determine their homologous relationships and regulatory networks. Therefore, this study provides new insights into the evolution of Arachis spp.Previous studies identified WRKY TFs in ifrunner , 28. Howr genome . TherefoA. monticola, A. hypogaea cv. Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner were obtained from GigaDB (http://gigadb.org/dataset/100453), NCBI , Peanut Genome Resource (http://peanutgr.fafu.edu.cn), and PeanutBase (https://www.peanutbase.org) databases [Arachis spp. [A. duranensis and A. ipaensis was based on a previous study [The released genome sequences of atabases \u201317, 29. atabases , and thehis spp. . The WRKus study .Arachis WRKY domains were aligned using MAFFT program [Six program , and the program . The ML program . The phyArachis species using the local BLAST program as per the following parameters: (1) the alignment region exceeds 80% of each sequence, (2) sequence identity over 80%, and (3) E-value \u2266 10\u201310 [Paralogs occur due to gene duplication events, while homoeologs are formed via polyploidy , 36. In \u2266 10\u201310 , 37, 38.cis-acting elements [WRKY genes were extracted using the genetic feature format (GFF) by the TBtools program [WRKY TFs are auto- and cross-regulated by the W-box elements , 39, 40. program . These s program .A. hypogaea WRKY sequences were used as a reference for predicting the protein\u2013protein interactions.The WRKY TFs were uploaded to the STRING database, and the A. monticola, A. hypogaea cv. Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner, respectively , A. hypogaea cv. Fuhuasheng , A. hypogaea cv. Shitouqi , and A. hypogaea cv. Tifrunner Fig.\u00a0, indicatArachis spp. have been sequenced and publicly released [Arachis genomes, or conserved orthologs among Arachis species can be analyzed to avoid variations. A previous study identified 158 WRKY TFs in A. hypogaea cv. Tifrunner [A. hypogaea cv. Tifrunner genome. Nevertheless, 158 WRKY TFs identified in the previous study contained 146 WRKY TFs from the updated genome. We utilized the same method to identify and analyze the evolution of WRKYs in Arachis spp.Several genomes of released , 15\u201317, released , 28. Howreleased found threleased . Second,ifrunner . In thisA. duranensis, A. ipaensis, synthetic allotetraploid (A. duranensis x A. ipaensis)4x, and A. hypogaea cv. Tifrunner and found that synthetic allotetraploid and A. hypogaea cv. Tifrunner had similar but lower drought tolerance than A. duranensis and A. ipaensis [A. hypogaea cv. Tifrunner and two diploid donors showed that A. hypogaea cv. Tifrunner lost ancestral drought genes, while new copies of drought tolerance genes lack origin function\u00a0after allotetraploidy [A. hypogaea cv. Tifrunner, we hypothesized that new WRKY TFs possibly have new functions and formed complex regulatory networks in tetraploid peanut species.Cultivated peanuts underwent allotetraploidy and domestication , 23, 44.ipaensis . These fraploidy . We founWRKY genes in cultivated peanuts. The number of W-box elements in WRKY genes was affected in cultivated peanuts compared with A. monticola. In addition, WRKY protein\u2013protein interaction results showed that A. hypogaea cv. Fuhuasheng and Shitouqi had similar protein interaction relations, while A. hypogaea cv. Tifrunner had a different protein interaction pattern. A. hypogaea cv. Fuhuasheng and Shitouqi are the progenitors of the Chinese peanut [A. hypogaea cultivars possibly underwent a similar domestication process. A. hypogaea cv. Tifrunner was bred in the USA in 2007 and is highly resistant to various diseases, unlike the Chinese peanut [A. hypogaea cultivars.This study showed that domestication affected e peanut , 16, suge peanut . This shArachis species. The number of WRKY TFs and their evolutionary patterns were compared, and the results revealed dynamic equilibrium in the number of WRKY TFs across the six Arachis spp. Notably, new WRKY TFs were retained while the old ones were lost after allotetraploidy. The present study also showed that domestication affected the WRKY TFs of cultivated peanuts. The WRKY TFs of A. hypogaea cv. Fuhuasheng and Shitouqi were subjected to a similar domestication process, while those of cv. Tifrunner underwent a different domestication process based on the protein\u2013protein interaction analysis.This study identified WRKY TFs in six Additional file 1: Table S1. WRKY genes in various Arachis species."} +{"text": "IJE, highlights the devastating impact of the COVID-19 pandemic on mortality across high-income countries.Our recent study of 29 countries, which was published in https://github.com/dkobak/excess-mortality],,,Two features of the pandemic\u2019s impact on Russian mortality stand out. First, similar to what we found for the USA, increased mortality in working, mid-life ages (20 to 60) accounted for 26% of the total life expectancy decline for women and 33% for men. Since at least 1960, Russia has been the country with the lowest male life expectancy and highest lifespan inequality in Europe, due to a continued burden of mid-life mortality.Second, sex differences in mortality observed in Russia are striking . Althoug,,,,Life expectancy losses in Russia in 2020 reveal that they were on a scale comparable to those observed in another similarly large and heterogeneous country, the USA. Russia\u2019s decline in life expectancy may even be larger in magnitude relative to the USA when compared with the projected life expectancy in 2020,This research project does not require ethics approval as it uses only macro data that are freely available online.https://github.com/oxforddemsci/ex2020].The replication files for this paper include customized functionality written in the R statistical programming language. The code, and all harmonized input and output data pertaining to our analysis, are hosted on GitHub [Conceptualization: J.M.A., J.S., I.K., R.K. Data curation: J.M.A., J.S., I.K., R.K. Formal analysis: J.M.A., J.S., I.K., R.K. Methodology: J.M.A., J.S., I.K., R.K. Software: J.M.A., J.S., I.K. Visualization: J.S. Project administration: J.M.A., J.S., I.K., R.K. Supervision: J.M.A., J.S., I.K., R.K. Writing\u2014original draft: J.M.A. Writing\u2014review and editing: J.M.A., J.S., I.K., R.K.British Academy\u2019s Newton International Fellowship grant NIFBA19/190679 ; ROCKWOOL Foundation\u2019s Excess Deaths grant ; Leverhulme Trust Large Centre Grant .None declared."} +{"text": "Alzheimer\u2019s disease (AD) is the most common neurodegenerative disorder affecting older adults globallyThis article does not require any human/animal subjects to acquire such approval.Not applicable.None.T.B.E.: conceptualization, writing \u2013 original draft preparation, writing \u2013 reviewing and editing, and visualization. H.C. and K.D.: data curation and writing \u2013 reviewing and editing.The authors declare that they have no financial conflict of interest with regard to the content of this report.None.https://orcid.org/0000-0003-3188-2272. E-mail: talhabmb@bgctub.ac.bdT.B. Emran, PhD, Associate Professor, Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh. Tel: +88 030 335 6193, Fax: +88 031 255 0224. We have read and understood the policy on the declaration of interests and have no relevant interests to declare. The responsibility for the content lies with the author, and the views stated herein should not be taken to represent those of any organizations or groups with and for which he works.Not commissioned, externally peer-reviewed."} +{"text": "Nature Communications 10.1038/s41467-022-33478-4, published online 11 October 2022Correction to: The original version of this Article contained an error in the first two sentences of the Acknowledgements section. The section only included initials of the people acknowledged \u201cWe are glad to thank B.O., A.B., N.E., S.-P.G., F.L., and S.M. for useful discussions. We also acknowledge M.J. and M.C.R. for fruitful discussions, for sharing their results in the course of our numerical studies and for enlightening us on the negligible role of band mixing.\u201dThe correct version includes the full last names \u201cWe are glad to thank B. Oblak, A. Bedroya, N. Englebert, S.-P. Gorza, F. Leo and S. Mukherjee for useful discussions. We also acknowledge M. J\u00fcrgensen and M. C. Rechtsman for fruitful discussions, for sharing their results in the course of our numerical studies and for enlightening us on the negligible role of band mixing.\u201dThis has been corrected in both the PDF and HTML versions of the Article."} +{"text": "Molecular Genetics & Genomic Medicine. 2019, 7(10), e00860. https://doi.org/10.1002/mgg3.860Xu, G. S., Li, Z. W., Huang, Z. P., Brundicardi, C. F., Jia, F., Song, C., Zou, H. J & Sun, R. F. \u201cMiR\u2010497\u20105p inhibits cell proliferation and metastasis in hepatocellular carcinoma by targeting insulin\u2010like growth factor 1\u201d. https://onlinelibrary.wiley.com), has been retracted by agreement between the authors, the journal Editor in Chief Dr. Suzanne Hart, and John Wiley & Sons. The retraction has been agreed due to problems in the original image preparation and data presentation, which undermine the reliability of the data presented as well as the article's conclusions.The above article, published online on 23 August 2019 in Wiley Online Library ("} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-022-10701-2, published online 27 April 2022Correction to: The Competing interests section in the original version of this Article was incorrect.\"The authors declare no competing interests.\"now reads:\"Both N.B. and A.R-G. declare no potential conflict of interest. M.O. has ties with Innovative Technology exploiting his patent regarding the Cyber-Sabots. J.-L.S. teaches the manual techniques evaluated in this work.\"The original Article has been corrected."} +{"text": "Helicobacter pylori (H. pylori) infection is chronic and etiologically linked to gastric cancer (GC) derived from gastric epithelium. The potential mechanism is complex, covering chronic inflammation, epithelial senescence, NF-\u03baB activation, the cytotoxin-associated gene A protein translocation, and related abnormal signaling pathways. In clinical practice, the test-and-treat strategy, endoscopy-based strategy, and (family-based) screen-and-treat strategy are recommended to detect H. pylori and prevent GC. It has been demonstrated that the decreasing annual incidence of GC is largely attributable to the management of H. pylori. This study reviews the current clinical practice of H. pylori on the detection and eradication, alternative treatment strategies, and related problems and advances, and hopes to contribute to the better clinical management of H. pylori. Helicobacter pylori (H. pylori) causes persistent infection in about 50% of the global population [H. pylori infected patients, accounting for 90% of all non-cardia GC (NCGC) and 20% of all cardia (CGC) cases, and H. pylori accounts for 15% of the global cancer burden [H. pylori infection [H. pylori induces the activation of NF-\u03baB of gastric epithelial cells and leukocytes [H. pylori, chronic inflammatory microenvironment, and abnormal apoptosis, which further leads to accumulating mutations and malignant transformation of gastric epithelial cells [CagA) is also a dominant factor leading to GC and activates oncogenic signaling pathways and inactivates tumor suppressors [H. pylori detection and eradication strategies are effective for GC prevention, before considering GC endoscopic or barium photofluorographic screening, especially in areas with high GC risks [H. pylori may exert systemic pathological effects, although its infection is localized [H. pylori and some extra-gastric diseases, such as unexplained iron-deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency. It is also recommended to detect and eradicate H. pylori in patients with these diseases [H. pylori infection may be involved in neurological diseases [H. pylori eradication.pulation . Gastricr burden . Its infnfection . Immunolnfection . In addiukocytes , contribal cells , 9. Howeal cells . Oncopropressors . H. pyloGC risks , 13. In diseases . Additiodiseases , hepatobdiseases , 18, anddiseases . More reH. pylori infection include age, ethnicity, levels of hygiene, and economic and social conditions [H. pylori infection [H. pylori are recommended to abolish inflammation and may contribute to the regression of CAG and metaplasia, especially in mild or moderate severity [13 UBT sensitivity 90\u2013100%/specificity 94\u2013100%), stool antigen test , serological test (sensitivity 76\u201384%/specificity 79\u201390%), endoscopy and biopsy-based diagnostic methods (histology (sensitivity 83\u201395.5%/specificity 95.4\u2013100.0%), rapid urease test , and culture (sensitivity 67.9\u201396.0%/specificity 79.4\u2013100.0%) [H. pylori infection, patient wishes, endoscopic findings, and medical policies. For example, test-and-treat strategy is recommendable for uninvestigated dyspepsia including functional dyspepsia with non-invasive tests [H. pylori and retest after eradication, as well as for children and patients after gastric surgery [H. pylori endoscopy-based strategy with biopsies including RUT and histology is recommended in dyspeptic patients, older patients, or patients with alarm symptoms, especially in populations with low prevalence of H. pylori infection (<10%). Kyoto classification based on conventional white light imaging (WLI) is reported with more than 80% diagnostic accuracy rate [H. pylori infection [H. pylori taction and 100% sensitivity when testing antibiotic resistance in patients with dyspepsia, which have similar or higher diagnostic ability than that of histological methods [H. pylori infection in a considerable proportion of patients with false negative results of conventional methods [H. pylori screen-and-treat strategy is addressed in communities with high GC risks, especially in young adults without precancerous lesion, which is the most cost-effective [H. pylori will pass by oral cavity before entering the stomach and potentially transmit mostly among family members, especially during childhood and adolescence, family-based screen and treat strategy is recommended in the family with GC family history or gastric mucosal precancerous lesions [H. pylori eradication can reduce GC risk in individuals who have a GC family history in first-degree relatives [H. pylori detection and screening [H. pylori including antigens /antibodies, oligonucleotides (DNA), and enzymes (urease enzyme) maybe via electrochemical/optical/piezoelectric/microfluidic based biosensor platforms, although challenges in the fabrication of biosensors exist, such as transducer selection, bio-recognition element, and their proper immobilization [H. pylori infection from the view of metabolism [The risk factors for nditions , 21. GC nfection . Timely severity . Diagnos\u2013100.0%) , 24. Metve tests \u201328. UBT surgery , 30. Seracy rate . Image-enfection . Furthernfection . Regardi methods \u201336. dPCR methods . Maastri methods . PCR or methods \u201340. The ffective . For areelatives and is celatives . Serologelatives . Rapid uelatives Additioncreening . For thelization . Volatiltabolism , 48.H. pylori infection can be cleared only by medical eradication treatment [H. pylori [H. pylori through one endoscopic examination [Presently, chronic reatment . The annreatment , 51, mai. pylori , 52, 53.. pylori . STT is . pylori . The cho. pylori . STT sho. pylori , 56. In . pylori , 57. In . pylori , 55, 58.. pylori , 60. Pro. pylori . Related. pylori . Another. pylori \u201365. Furt. pylori , 67. The. pylori . Apart f. pylori , 69. Addmination . These rH. pylori management (Hp-EuReg) and finds 23% pretreatment resistance rate to clarithromycin, 32% to metronidazole, and 13% to both. The modified intention-to-treat eradication rate is 81.5%. \u226590% eradication rate is only achieved by BQT or CT [H. pylori is shown tolerant to multiple antibiotics including amoxicillin, clarithromycin, and tetracycline [H. pylori eradication [Antibiotic resistance has been increased in most WHO regions. >15% primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin are reported in all WHO regions. Antibiotic resistance is a major driver of eradication failure. For example, resistance to clarithromycin is associated with the failure of clarithromycin-containing regimens (odds ratio: 6.97) . One resQT or CT . In AsiaQT or CT . The mecQT or CT . Some faQT or CT . Biofilmacycline . Coccoidacycline . These racycline . Higher acycline or thoseacycline . One studication . Anotherdication .H. pylori, and living and eating habits), host factors , and organism factors [H. pylori or follow-up system. Routine post-eradication retest and ensuring timely follow-up eradication are important and should be focused on.When receiving eradication treatment, the most common problems are AEs induced by drugs. One meta-analysis based on Hp-EuReg has reported that 7% taste disturbance, 7% diarrhea, 6% nausea, and 3% abdominal pain are the most frequent AEs. The majority of AEs are mild (57%), 6% are severe, and only 0.08% are serious. The average duration is 7 days. The treatment compliance rate is 97%, and the discontinuation rate due to AEs is 1.3%. These AEs are usually mild with limited duration and without apparently interference on treatment compliance . After rization) , 87\u201389. ization) , maybe bH. pylori eradication if H. pylori test is positive to promote the ulcer healing and prevent recurrence [H. pylori eradication [H. pylori has been eradicated also have a higher long-term risk of NVUGIB, particularly in elder patients (>45 years), which increased significantly after the first two years following eradication [It is recommended that patients with hemorrhagic peptic ulcer diseases should receive currence . Delays currence , 93. Howcurrence . The hosdication , 96. Patdication . Hidden dication . Health dication .H. pylori eradication reduces GC, the risk of GC after H. pylori eradication still exists. 0.21% of H. pylori-eradicated patients develops GC during a mean follow-up of 4.7 years [H. pylori. Atrophy can also progress to GC in some conditions, such as advanced chronic atrophy gastritis and accompanied incomplete metaplasia, invisible dysplasia, genetic alterations of stem cells, or epithelial\u2013mesenchymal transition [H. pylori infection, such as mitochondrial changes, senescence, (epi)genetic alterations, and dysbiosis of gastric microbiome, contribute to GC independent of H. pylori [Although .7 years . There a.7 years . Existinansition . The revansition . Additio. pylori . In clin. pylori , 103. He. pylori . Some ad. pylori . Gas bio. pylori . Another. pylori . GC predH. pylori can efficiently evade innate immune detection and persistently colonize in the inhospitable environment with an acidic pH < 3 and a rapidly renewing gastric epithelium [H. pylori cannot fully ensure the continued protection [H. pylori would be effective to achieve prophylaxis or eradication and reduce the prevalence of gastric diseases [+ and CD8+ epitopes [Escherichia coli enterotoxin as mucosal adjuvant to increase the immunogenicity, oral delivery of live vector vaccines expressing H. pylori antigens to stimulate durable immunity , and intramuscular delivery of H. pylori subunits vaccines with aluminum hydroxide adjuvant [H. pylori vaccines could reduce bacterial load and sometimes provide sterilizing immunity, whereas ineffective or only partially effective results were achieved in larger animals and patients [H. pylori treatment are shown with higher successful eradication rate [H. pylori effects including drug-resistant H. pylori by \u03b1-helical structure, being cationic, with high positive charge and isoelectric point [H. pylori [H. pylori with/without drug resistance. A H. pylori-targeted PS can avoid undesirable phototoxicity to normal cells. Multiple 3SL conjugated poly-L-lysine based photomedicine with a H. pylori targeted PDT strategy using an endoscopic laser system has been proposed [H. pylori, and the use is still underdeveloped, such as the preparation of specific lytic phage [H. pylori, suggesting their potential as alternative options for the management of H. pylori infection [ithelium . Successotection . Vaccinadiseases . A prophdiseases . The maidiseases , and theepitopes . Some vadjuvant \u2013120. H. patients . Most vapatients . Howeverpatients . It is pion rate , 124. Anic point . They ha. pylori . Photodyproposed . Phage tic phage . Some stnfection (Figure H. pylori is usually acquired in childhood. They can safely colonize around the gastric glands and further induce chronic inflammation, NF-\u03baB activation, and CagA translocation, which cause damage and the loss of gastric glands and even neoplastic transformation and carcinogenesis. Therefore, the detection and eradication of H. pylori are necessary. The regimen option is currently based on antibiotic resistance and experience. Some problems after eradication require our concerns including recurrence, the risk of NVUGIB, and the risk of GC. Routine susceptibility test and retest, regular and careful endoscopic surveillance, and health education contribute to controlling or solving these problems to achieve better H. pylori management. Additionally, potential alternative treatments may aid the current antibiotics treatment. The development of vaccine may be one solution to achieve a wide range of preventive effects and eradication treatment.The chronic infection of"} +{"text": "We appreciate the engagement in the Commentaries for our adolescent amenorrheic athletes; an important determinant for fracture risk.Although our concern related to the use of population normative Z-scores mainly referred to potentially overlooking symptoms of low energy availability (LEA) in high-impact (HI) sport athletes, also overlooking athletes at high risk for fractures is worrying. About 10% of all sports-related injuries, being as high as 30% in running, are stress fractures, depriving athletes from sport participation . The inaInterestingly, DXA does not distinguish cortical from trabecular bone mass, whereas trabecular bone mass is early to deteriorate with persistent overload or poor recovery, the BMD changes may be masked in cortical-dominated bone areas . This waAs such, \u201cnormal\u201d BMD Z-scores, still being lower than expected for a HI athlete, may indicate a high risk for bone stress injury, and some of the explanations may be impaired bone quality. This is not measurable by DXA but has typically been reported by BMD Z-scores around \u201c0\u201d or less. As long as values above \u22121 are considered clinically normal, we may overlook athletes at high risk for fractures, also leaving them at high risk for the many other clinical complications by relative energy deficiency in sport (RED-S), if the reason for impaired bone quality relates to LEA. Hence, in contrast to van Weijer et al. (No conflicts of interest, financial or otherwise, are declared by the authors.T.F.M. drafted manuscript; K.L.J., M.K.T., J.K.S.-B., and T.F.M. edited and revised manuscript; K.L.J., M.K.T., J.K.S.-B., and T.F.M. approved final version of manuscript."} +{"text": "Fusarium spp. are among the most important plant pathogens in the world. A survey on maize leaf blight was carried out in Heilongjiang province from 2019 to 2021. Based on morphological characteristics and a phylogenetic analysis on translation elongation factor (tef1) and second-largest subunit of RNA polymerase II (rpb2) genes, 146 Fusarium isolates were obtained and grouped into 14 Fusarium species, including F. ipomoeae (20.5%), F. compactum (17.1%), F. sporotrichioides (9.59%), F. graminearum (9.59%), F. citri (8.9%), F. asiaticum (6.85%), F. verticillioides (6.85%), F. acuminatum (5.48%), F. glycines (5.48%), F. temperatum (2.74%), F. armeniacum (2.74%), Fusarium sp. (2.05%), F. flagelliforme (1.4%), and F. annulatum (0.68%). The Fusarium incarnatum-equiseti species complex was the most prevalent, indicating an evolving occurrence of the Fusarium species causing maize leaf blight. The typical symptoms observed on the maize leaves were oval to long strip lesions, with a gray to dark gray or brownish red coloration in the center and a chlorotic area at the edges. Based on the tef1 gene, seven haplotypes of FIESC were identified in Heilongjiang province, suggesting a population expansion. This is the first report of F. ipomoeae, F. compactum, F. flagelliforme, F. citri, F. sporotrichioides, F. graminearum, F. asiaticum, F. acuminatum, F. glycines, F. temperatum, F. armeniacum, Fusarium sp., and F. annulatum causing maize leaf blight in Heilongjiang province, China. The current research is informative for managing disease, exploring the phylogenetic relationship among Fusarium species, and clarifying the diversity of Fusarium species associated with maize leaf blight. Fusarium spp. can cause several diseases in maize, such as Fusarium ear rot /(N \u00d7 9), where n is the number of infected inoculation leaves corresponding to each disease rating, and N is the total number of inoculation leaves. Disease incidence was computed by following formula: disease incidence = number of diseased leaves/total number of inoculated leaves of living maize plants. A least significant difference (LSD) test was used for statistical analysis at a significance level of p < 0.05 with the Statistical Package for Social Sciences (SPSS) software . All re-isolated pathogens from inoculated maize leaves were identified using morphological and molecular methods mentioned above. Each experiment was repeated two times.Disease severity (DS) and disease incidence (DI) were assessed 14 days post-inoculation. DS was measured based on a 0\u20139 scale described by Rafael et al. and Xu etef1 gene sequences [Fusarium species on account of the limited number of isolates from those species obtained in the current study.DNA Sequence Polymorphism software version 6 was used to individually determine the DNA polymorphism relative degree of the equences . Furtherequences ,29. DNA tef1 gene sequences of 70 FIESC isolates using PopART v. 1.7 (Allan Wilson Centre Imaging Evolution Initiative) to evaluate genealogy pattens of the haplotypes [Haplotype networks were individually generated based on the plotypes . The aliplotypes .Fusarium isolates were obtained from symptomatic maize leaves in China , F. sporotrichioides, F. armeniacum, F. asiaticum, F. graminearum, Fusarium sp., F. acuminatum, F. glycines, F. annulatum, F. temperatum, and F. verticillioides using a BLAST analysis and caused maize leaf blight in the inoculation study. In addition, F. graminearum showed the highest virulence, followed by Fusarium sp., F. glycines, F. acuminatum, F. compactum, F. temperatum, F. asiaticum, F. citri, F. verticillioides, F. armeniacum, F. ipomoeae, F. annulatum, F. sporotrichioides, and F. flagelliforme.Two weeks after inoculation, the pathogenicity test revealed that all the Fusarium species could cause similar maize leaf blight symptoms . Small oectively . MoreoveF. ipomoeae isolates, 25 F. compactum isolates, 2 F. flagelliforme isolates, and 13 F. citri isolates) obtained in this study were used to determine evolutionary relationships among the haplotypes. Most haplotypes within one species were closely related and separated by one to three mutations.The haplotype networks based on the tef1 gene sequences of 70 FIESC isolates and F. citri haplotype (Hap 7) were observed in external parts of the haplotype network and showed more mutation events from their nearest haplotypes, which indicated that these two species have an older evolutionary relationship. In addition, the high haplotype diversity and low nucleotide diversity indicated a population expansion [The haplotype groups of FIESC associated with maize leaf blight were first identified in this work. The predominant haplotype (Hap 1) represented multiple locations . It is well-known that older haplotypes may have a wider geographic distribution, which suggests that Hap 1 has lasted in the population for a long time . The resxpansion .Fusarium species causing maize leaf blight in Heilongjiang province, China, and is the first to report F. ipomoeae, F. compactum, F. flagelliforme, F. citri, F. sporotrichioides, F. graminearum, F. asiaticum, F. verticillioides, F. acuminatum, F. glycines, F. temperatum, F. armeniacum, Fusarium sp., and F. annulatum as the causal agents. Fusarium can cause various maize diseases; therefore, clarifying the population composition of Fusarium spp. on maize leaves will provide information for the overall control of maize diseases.In conclusion, the current study focused on the pathogenicity and genetic diversity of"} +{"text": "Nature 10.1038/s41586-022-04554-y Published online 6 April 2022Correction to: In the version of this article initially published, there were errors in the affiliations for K. Im , J. Lerch , S. Villeneuve and X. N. Zuo (incorrect affiliation numbers listed), H. Yun , and H. J. Zar (extra affiliation shown). In addition, the affiliation numbers for all authors listed in the consortium membership section were incorrect by 1\u20133 digits. The errors have been corrected in the HTML and PDF versions of the article."} +{"text": "Scientific Reports 10.1038/s41598-022-14983-4, published online 27 June 2022Correction to: The original version of this Article contained errors in the spelling of the authors Murat Ak and Nursima Ak, which were incorrectly given as A.K. Murat and A.K. Nursima, respectively.The Author contribution statement now reads:\u201cL.P. designed and constructed the experiments and wrote the draft of the manuscript. M.A. and N.T. verified the ground truth of the experimental dataset and revised the manuscript. S.Z., S.A., A.K., M.Y., M.E. and N.A. verified the ground truth of the experimental dataset. L.C. revised the manuscript. R.C. supervised the whole project.\u201dThe original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-022-19981-0, published online 20 September 2022Correction to: The Author Contributions section in the original version of this Article was incomplete.\u201cC.Y. programmed the simulations, prepared all figures, and wrote the main manuscript text, Q.Y. helped with modifying the manuscript text. All authors reviewed the manuscript.\u201dnow reads:\u201cC.Y., Q.Y., and C.S. formulated the model; C.Y., Q.Y., and C.S. analyzed the data; C.Y., Q.Y., and C.S. developed the methodology; C.Y. developed the simulation tool; C.Y., Q.Y., and C.S. analyzed the results and contributed to the discussions; C.Y., Q.Y., and C.S. contributed to the writing. All authors reviewed the manuscript. \u201dThe original Article has been corrected."} +{"text": "Primula (Primulaceae) comprises more than 500 species, with 300 species distributed in China. The contradictory results between systematic analyses and morphology-based taxonomy make taxonomy studies difficult. Furthermore, frequent introgression between closely related species of Primula can result in non-monophyletic species. In this study, the complete chloroplast genome of sixteen Primula obconica subsp. obconica individuals were assembled and compared with 84 accessions of 74 species from 21 sections of the 24 sections of the genus in China. The plastome sizes of P. obconica subsp. obconica range from 153,584 bp to 154,028 bp. Genome-wide variations were detected, and 1915 high-quality SNPs and 346 InDels were found. Most SNPs were detected in downstream and upstream gene regions (45.549% and 41.91%). Two cultivated accessions, ZP1 and ZP2, were abundant with SSRs. Moreover, 12 SSRs shared by 9 accessions showed variations that may be used as molecular markers for population genetic studies. The phylogenetic tree showed that P. obconica subsp. obconica cluster into two independent clades. Two subspecies have highly recognizable morphological characteristics, isolated geographical distribution areas, and distinct phylogenetic relationships compared with P. obconica subsp. obconica. We elevate the two subspecies of P. obconica to separate species. Our phylogenetic tree is largely inconsistent with morphology-based taxonomy. Twenty-one sections of Primula were mainly divided into three clades. The monophyly of Sect. Auganthus, Sect. Minutissimae, Sect. Sikkimensis, Sect. Petiolares, and Sect. Ranunculoides are well supported in the phylogenetic tree. The Sect. Obconicolisteri, Sect. Monocarpicae, Sect. Carolinella, Sect. Cortusoides, Sect. Aleuritia, Sect. Denticulata, Sect. Proliferae Pax, and Sect. Crystallophlomis are not a monophyletic group. The possible explanations for non-monophyly may be hybridization, polyploidization, recent introgression, incorrect taxonomy, or chloroplast capture. Multiple genomic data and population genetic studies are therefore needed to reveal the evolutionary history of Primula. Our results provided valuable information for intraspecific variation and phylogenetic relationships within Primula.The genus Ottelia acuminata, which consists of six phenotypic varieties, of which the chloroplast genome was successfully divided it into two conspecific varieties [Species are fundamental units of biodiversity, but the boundaries of species are still confusing , especiaarieties , thus prIntraspecies genetic and phenotypic variation is essential to drive plant evolution and adaptation , whereasPrimula (Primulaceae) includes more than 500 species, with 300 species distributed in China [Primula was found in China . From the morphological evidence, it was generally accepted that there are seven subgenera worldwide . However, this assumption was inconsistent with molecular phylogenetic analyses, because most of these subgenera were found to be non-monophyletic [Auricula [Proliferae, Sect. Amethystina, Sect. Petiolares, Sect. Muscarioides, Sect. Souliei, Sect. Sikkimensis, Sect. Soldanelloides, and Sect. Pycnoloba [The genus in China . The cenphyletic ,11. Furtphyletic ,13,14. CAuricula , Sect. Pycnoloba .Primula, including within the same species (P. obconica and P. oreodoxa). Species such as P. obconica subsp. obconica are heterostylous, whereas species such as P. obconica subsp. parva are homostylous [Primula, such as P. veris \u00d7 P. vulgaris and P. elatior \u00d7 P. vulgaris [Primula [Heterostylous and homostylous taxa both occur in ostylous ,18. The ostylous . For thivulgaris . Hybridi[Primula , which mPrimula obconica is widely distributed in subtropical China. It contains six subspecies, including P. obconica subsp. obconica, P. obconica subsp. werringtonensis, P. obconica subsp. parva, P. obconica subsp. begoniiformis, P. obconica subsp. nigroglandulosa, and P. obconica subsp. fujianensis [P. obconica subsp. obconica, all have restricted areas of distribution in the Yunnan, Sichuan, and Fujian provinces of China. P. obconica shows a high variation in morphological traits at the intraspecific level, mainly in plant size and leaf blade indumentum [P. obconica was confused, for example, P. obconica subsp. werringtonensis, as recognized by Smith, was treated as a separate species, P. werringtonensis. In addition, P. obconica subsp. parva has been treated as a separate species of P. parva [P. obconica subsp. obconica has been widely cultivated in Europe and North America [P. obconica subsp. obconica, but were not detected in wild species [Primula breeding in the horticultural market [ianensis ,22. Thesdumentum . Due to P. parva ,24. Sinc America . Primin species ,27. Wildl market .Primula. Chloroplast genomes are widely used in phylogenetics, thus providing a solution for solving the evolutionary history of Primula. In this study, we analyzed a total of 100 accessions of 74 species from 21 sections of the 24 sections of the genus in China. Our main goals were to: (1) explore the intraspecific variation in P. obconica subsp. obconica; (2) decipher the taxonomic delimitation of the P. obconica complex; (3) reveal the phylogenetic relationships of 21 sections of Primula in China and test morphology-based taxonomy with molecular data.The accurate delimitation of species boundaries is crucial for nature conservation and management. In rapidly evolved genera, hybridization and introgression are common, which enhance the difficulty of phylogenetic analyses. Furthermore, molecular systematic studies are inconsistent with the morphology-based taxonomy of Thirteen wild accessions were collected from the Sichuan, Yunnan, Hubei, and Hunan provinces. Samples were collected across China, including the main distribution areas of the species. Sichuan, Hubei, and Hunan included two populations, and each population contained two wild accessions. Two Chinese-cultivated accessions were collected from the Wuhu (Anhui) flower market . All speP. obconica subsp. obconica (MK344754) plastome as a reference. Bandage was used to confirm that the assembly graph was circular [P. obconica [The de novo assembly of the clean data was performed on a GetOrganelle pipeline , with -tcircular . Assemblcircular . Organelobconica .P. obconica subsp. obconica (MK344754), was used as a reference. The Burrows\u2013Wheeler Aligner (BWA) version 0.7.17 was used to index and align the clean data to the reference chloroplast genome [P. obconica [P. obconica, the microsatellite identification (MISA) software tool was used, with 10, 6, 5, 3, 3, and 3 for mono-, di-, tri-, tetra-, penta-, and hexanucleotide sequences, respectively [The complete chloroplast genome of t genome , SAMtoolconica MK4754, wast genome . The proobconica . To idenectively .https://genome.lbl.gov/vista/mvista/submit.shtml, accessed on 30 August 2021) with a shuffle-LAGAN model, and HBD1 as a reference. To compare the IR/SC boundaries of different subspecies within P. obconica, the IRscope web service was used to visualize the result.A comparative analysis of the chloroplast genomes of sixteen wild and cultivated accessions was carried out using mVISTA online software as an outgroup. Seventy-seven protein-coding genes were extracted, aligned, and merged by PhyloSuit version 1.1.2 [To study the relationships between on 1.1.2 . Maximumon 1.1.2 , with a P. obconica subsp. obconica had a conventional quadripartite structure characteristic of angiosperm plastomes, with an LSC, SSC, and two IR regions (ycf3 and clpP) contained two introns. The ycf3 and clpP genes were also trans-spliced into three exons chloroplast genome reference. A total of 1915 high-quality SNPs and 346 InDels were detected . Moreover, ycf1 contained the most abundant number of SNPs (133) , but when compared with the overall SNPs detected in the ycf1 gene (133), it seems that the ycf1 gene had more variations at the intraspecific level (The clean data of 16 accessions were mapped onto the detected . ZP2 harPs (133) A. In the of SNPs B. The re of SNPs . One hun of SNPs C. Most oic level D.A total of 401 SSRs were identified, including 317 mononucleotide, 31 dinucleotide, 39 tetranucleotide, and 14 pentanucleotide repeats . Two culPrimula subsp. obconica exhibited the same pattern in content and the number of genes in the IR/LSC and IR/SSC boundary regions, some differences still existed , but three species of Sect. Obconicolisteri were more closely related to Sect. Monocarpicae and Sect. Cortusoides. P. obconica subsp. obconica was not a monophyletic species in our results, it was divided into two distinct related clades. Two subspecies of P. obconica were clustered into a separate branch. The Sect. Bullatae was clustered to the rest of the Sect. Monocarpicae. P. calyptrata belonged to Sect. Carolinella, forming a separate branch. The result supported the hypothesis that Sect. Auganthus and Sect. Bullatae comprise a monophyletic section. Cluster I contained seven sections, including Sect. Aleuritia, Sect. Minutissimae, Sect. Soldanelloides, Sect. Denticulata, Sect. Capitatae Pax, Sect. Sikkimensis, Sect. Souliei, and Sect. Primula. Four of five species of Sect. Aleuritia clustered to one clade, but the placement of P. gemmifera in the phylogenetic tree resulted in the non-monophyly of Sect. Aleuritia. The Sect. Minutissimae and Sect. Soldanelloides clustered to a sister group. Three sections were mixed in the phylogenetic tree. Our result only supported Sect. Sikkimensis and Sect. Minutissimae forming a monophyletic group in cluster II. Cluster II contained eight sections, including Sect. Proliferae Pax, Sect. Petiolares, Sect. Amethyatina, Sect. Crystallophlomis, Sect. Ranunculoides) formed cluster III, in which Sect. Proliferae Pax and Sect. Crystallophlomis did not form a monophyletic section. Four species in Sect. Proliferae Pax formed a clade sister to Sect. Amethyatina. One species is of special interest in cluster III: P. handeliana is ascribed to Sect. Crystallophlomis, but it formed a distinct clade with Sect. Crystallophlomis and was more closely related to Sect. Ranunculoides. The monophyly of Sect. Ranunculoides is strongly supported in this study.The rest of the sections [Selaginella tamariscina (1641 InDels and 1213 SNPs) [Goodyera schlechtendaliana (414-2133 InDels and 200-844 SNPs) [P. obconica subsp. obconica. The cultivated accession ZP2 harbored the largest number of SNPs (1002), and wild accessions of YN (YN1 and YN2) had the fewest number of SNPs (335). In contrast, the genomic variants detected in wild rubber trees (193) were much larger than those detected in cultivated (91) accessions [P. obconica subsp. obconica (MK344754) than other accessions. Among the protein-coding genes, 15 genes had a relatively higher number of SNPs . Moreover, SNPs were especially abundant in the ycf1 gene (133), which was also reported in Ricinus communis [matK, psbA, ndhF, and ycf1 genes were used as cpDNA barcodes to identify closely related species [ycf1 gene was considered as the core barcode of land plants [Primula but were also varied among the different varieties of P. obconica [P. obconica subsp. obconica, but only 131 SNPs were common, which showed higher variation at the intraspecific level of P. obconica subsp. obconica. These samples were collected from different geographic locations, and climatic variation may be the main driver triggering genomic variations [Although plastomes have the properties of uniparental inheritance and a low frequency of recombination, these features have also prompted plastomes to maintain highly conserved features; however, mutations at the intraspecific level have still occurred, such as in 19 SNPs) , Selagin13 SNPs) , and fiv44 SNPs) . A totalcessions . Many ofica MK34454 than onica MK3454 than o species ,49,50. Mobconica . In totariations . The Snpriations .P. obconica subsp. obconica.Due to their high abundance and variability, especially of the repeat and motif structures of SSRs in the cp genome, the SSRs have been used for population genetics and evolution studies ,55. SeveatpF, petD, rpl16, ndhA, and ycf1. These five genes were in both the 16 P. obconica subspecies and four subspecies. In the intergenic regions, the four subspecies showed more divergence in rps16-trnQ-UUC, atpF-atpH, psbM-trnD-GUU, ycf3-trnS-GGA, rbcL-psaI, ycf4-cemA, and psbE-petL. These variation regions were different from those detected within P. obconica subsp. obconica, indicating the divergence between the four subspecies and P. obconica subsp. obconica.Similar to other angiosperm studies, protein-coding sequences were more conserved than intergenic regions, and the LSC regions were the most divergent ,59. In tHevea brasiliensis, in which there are variations in gene number and the length of ycf1 spanning the boundary of the SSC region [P. obconica subsp. obconica. There were apparent variations in some genes spanning the boundary of the SC/IR region. These variations are likely associated with phylogenetic signals, for example, the ndhF spanning the boundary of the IRb/SSC region was consistent with the clade of the phylogenetic tree in P. obconica subsp. obconica.The expansion and contraction between IR and the single-copy (SC) boundary regions are considered the main causes of the cp genome variation . There hC region . In our Primula and the place of origin of other land plants [P. obconica originated from the Yunnan and Sichuan provinces [P. obconica were shown in phylogenetic trees and PCA analysis, which were based on data regarding SNPs, InDels, and 77 shared protein-coding genes. Our results were consistent with the finding that P. obconica was split into the Sichuan-Central group and Yunnan-Eastern group [P. obconica subsp. obconica was separated into two groups, consistent with the result of our SSR analysis [Dodecatheon dentatum, Dodecatheon jeffreyi, Primula veris, and Primula vulgaris [P. obconica subsp. obconica. Southwest China is considered the biodiversity center of d plants ,64. Migrd plants . Considerovinces ,67. Two rn group . Our phyanalysis . Non-monanalysis . Whetheranalysis . Howevervulgaris ,73. The vulgaris . Moreovevulgaris . Based oPrimula, such as P. sikkimensis [P. interjacens (HSP: 0.4618) [P. obconica. Prior research has implied that the genetic differentiation in P. obconica was mainly caused by geographical barriers and seed dispersal mechanisms [P. obconica subsp. obconica. Many factors can affect genetic diversity within species, such as geographic distribution, breeding system, and isolation by gene flow . Gene fl 0.4032) , and P. 0.4618) . Accordirodents) ,80. In tP. obconica subsp. werringtonensis is distributed in the west of Sichuan, with a margin of usually sinuate-lobulate that is distinguished from P. obconica subsp. obconica. P. obconica subsp. begoniiformis possesses slender petioles, a leaf blade of ovate-rotund to suborbicular shape, and a margin of crenate-lobulate that differs from P. obconica subsp. obconica. P. obconica subsp. parva and P. obconica subsp. fujianensis all have the characteristic of scapes that are shorter than leaves. The four subspecies all have very small populations and are restricted to the Yunnan, Sichuan, and Fujian provinces of the Chinese mainland. A previous study inferred that P. obconica subsp. fujianensis originated from P. obconica subsp. obconica, and the east of Yunnan populations originated from the Sichuan population. Moreover, the variation in genetics between the four subspecies and P. obconica subsp. obconica was not obvious [P. obconica subsp. fujianensis and P. obconica subsp. werringtonensis were nested within P. obconica subsp. obconica, suggesting the two subspecies had genetic variation overlapping the P. obconica subsp. obconica populations. Additionally, P. obconica subsp. parva and P. sinolisteri subsp. sinolisteri were clustered in a sister clade, while P. obconica subsp. begoniiformis and P. ambita were closely related. The two subspecies have highly recognizable morphological characteristics, isolated geographical distribution areas, and a distinct phylogenetic relationship compared with P. obconica subsp. obconica. We propose the elevation of the two subspecies of P. obconica to separate species, P. begoniiformis and P. parva. obvious . In our Primula, such as Sect. Obconicolisteri, Sect. Monocarpicae, Sect. Cortusoides, Sect. Carolinella, Sect. Aleuritia, Sect. Denticulata, and Sect. Crystallophlomis. Three possible explanations may aid in the interpretation of these phenomena. Firstly, genetic drift, ancestral polymorphism, polyploidization, and recent introgression lead to sister species becoming reciprocally monophyletic. Gene exchange among interspecies may lead to the combination of genetic components of different ancestors, in which case, phylogenetic analysis between hybrids will be more challenging. Previous research has demonstrated that natural hybridization is common and has been detected between interspecies in Primula [Primula species were bees and butterflies, there were 12 families and 22 species of flower-visiting insects of Primula lithophila [Primula outcrossing. Polyploidization has been detected in Primula, suggesting there was different ploidy in or between sections [Aconitum [P. egaliksensis were clustered to Sect. Aleuritia [Pomatosace, Anagallis, Soldanella, and Bryocarpum in Primulaceae has been attributed to convergent evolution [P. secundiflora has long been treated as a member of Sect. Sikkimensis based on the campanulate corolla, but phylogenetic analysis suggested it should be placed in Sect. Proliferae Pax [P. subansirica was found to belong to Gesneriaceae [Primula [Our phylogenetic tree showed multiple non-monophyletic sections of Primula ,81,82. Tthophila . Multiplsections . FurtherAconitum ,86,87. Pleuritia . Polyplovolution . Furthererae Pax . Recentleriaceae . Thirdly[Primula ,93,94. Primula worldwide [Auganthus; only one section belonging to subgen. Carolinella was nested within subgen. Auganthus. Our phylogenetic analysis implied neither subgen. Auganthus nor subgen. Carolinella are monophyletic taxa, consistent with previous analyses [Carolinella with its calyptrate capsule can be distinguished from other subgenera. Previous research has implied that the calyptrate capsule might have evolved multiple times in Primula [P. calyptrata and P. kwangtungensis were separated from each other and distantly related. Previous studies have also been performed on Sect. Obconicolisteri. These results were inconsistent with our study, due to insufficient samples and not being combined with other sections in previous phylogenetic analyses [Obconicolisteri is not a monophyletic group. Three species of this section were clustered with Sect. Monocarpicae and Sect. Cortusoides. To make Sect. Obconicolisteri monophyletic, these three species should be excluded. P. dumicola and P. oreodoxa were treated as members of Sect. Obconicolisteri, but appear closer to Sect. Monocarpicae. Regarding the two species with calyx broadly campanulate and P. dumicola with calyx margin entire, these characteristics are more similar to Sect. Monocarpicae. Besides, P. calyptrata and P. handeliana possess a distant phylogenetic relationship with their natural morphology sections. Phylogenetic analyses based on protein-coding genes were also performed by Ren (2018), implying that P. calliantha and P. woodwardii did not have the closest relationship [Richard (2003) recognized seven subgenera and thirty-eight sections in orldwide . Our phyanalyses ,95,96. Tanalyses ,16,69. Otionship . MoleculPrimula (Sect. Primula) and subgen. Aleuritia. The subgenus Aleuritia is a large group in Primula with 19 sections. Our results were largely congruent with previous research that subgen. Aleuritia is paraphyletic [P. gemmifera is endemic to China, mainly distributed in southern Gansu, western Sichuan, and northeastern Tibet. In our results, P. gemmifera is grouped with Sect. Capitatae Pax and Sect. Denticulata and form a well-supported clade. The non-monophyly of Sect. Aleuritia is consistent with the conclusion made by Ren (2015) [Aleuritia is also supported by other research [Sikkimensis is well supported in our result. Clade II included subgen. phyletic ,99. P. gn (2015) . Howeverresearch ,101, thoPinnatae (Sect. Ranunculoides), subgen. Aleuritia, and subgen. Auriculastrum (Sect. Amethyatina). The results strongly supported the monophyly of Sect. Ranunculoides and Sect. Petiolares. Four species were clustered to Sect. Petiolares and Sect. Amethyatina. The Sect. Proliferae Pax was paraphyletic. The result differed from cpDNA and ITS analyses, owing to the absence of species of Sect. Petiolares and Sect. Amethyatina in previous research. Hu and Kelso (1996) renamed Sect. Pinnatae as a new section, Sect. Ranunculoides, and transferred P. filchnerae into Sect. Auganthus. Subsequently, this treatment was authenticated by molecular phylogenetic analysis [P. filchnerae in Sect. Auganthus. Furthermore, Sect. Auganthus and Sect. Ranunculoides were two monophyletic and distantly related sections.Clade III contained subgen. analysis . Our phyP. obconica subsp. obconica were identified to have different lengths, which were mainly caused by variations in the LSC and SSC regions. Highly genome-wide variations were detected. Most SNPs were detected in downstream and upstream gene regions (45.549% and 41.91%). Multiple sequence divergent regions and SSRs found in this study would provide useful information for population genetic analyses in P. obconica. The phylogenetic tree showed that P. subsp. obconica can be split into two independent clades. The taxonomy of the P. obconica complex was redefined in this text. We elevated two subspecies of P. obconica to separate species. Our phylogenetic tree was largely inconsistent with the previous morphology-based taxonomy. Twenty-one sections of Primula were mainly divided into three clades. The monophyly of Sect. Auganthus, Sect. Minutissimae, Sect. Sikkimensis, Sect. Petiolares, and Sect. Ranunculoides were well supported in the phylogenetic tree. The Sect. Obconicolisteri, Sect. Monocarpicae, Sect. Carolinella, Sect. Cortusoides, Sect. Aleuritia, Sect. Denticulata, Sect. Proliferae Pax, and Sect. Crystallophlomis were not a monophyletic group. Several sections were represented by only one species, the phylogenetic relationships of these sections will need a larger number of samples in future studies. Although chloroplast genomes have the properties of uniparental inheritance and low frequency of recombination, these features have prompted plastomes to possess highly conserved features. However, variations at the intraspecies level have still occurred. Sixteen plastome genomes of"} +{"text": "Weissella (W.) beninensis, W. diestrammenae, W. fabalis, W. fabaria, W. ghanensis, and W. uvarum type strains were sequenced and analyzed. Moreover, the ability of these strains to metabolize 95 carbohydrates was investigated, and the genetic determinants of such capability were searched within the sequenced genomes. 16S rRNA gene and genome-based-phylogeny of all the Weissella species described to date allowed a reassessment of the Weissella genus species groups. As a result, six distinct species groups within the genus, namely, W. beninensis, W. kandleri, W. confusa, W. halotolerans, W. oryzae, and W. paramesenteroides species groups, could be described. Phenotypic analyses provided further knowledge about the ability of the W. beninensis, W. ghanensis, W. fabaria, W. fabalis, W. uvarum, and W. diestrammenae type strains to metabolize certain carbohydrates and confirmed the interspecific diversity of the analyzed strains. Moreover, in many cases, the carbohydrate metabolism pathway and phylogenomic species group clustering overlapped. The novel insights provided in our study significantly improved the knowledge about the Weissella genus and allowed us to identify features that define the role of the analyzed type strains in fermentative processes and their biotechnological potential.In this study, the genomes of the Weissella is a genus belonging to the phylum Firmicutes, order Lactobacillales, and family Lactobacillaceae. Weissella species are nonspore-forming, catalase-negative, and Gram-positive bacteria with either a coccoid or rod shape. They have a widespread occurrence, being isolated from various ecological niches such as soil (mainly Weissella soli) , W. confusa (comprising W. cibaria and W. confusa), W. halotolerans , W. paramesenteroides , and W. beninensis species groups, respectively.The genus s et al. , to dateo et al. who, updo et al. , clusterWeissella species have been described, including W. bombi and BCCM/LMG (http://bccm.belspo.be/db/lmg_search_form.php), whereas the W. uvarum B18NM42 type strain (=DSM 28060T) was kindly provided by Dr. Aspasia Nisiotou from the Institute of Technology of Agricultural Products, Hellenic Agricultural Organization Lykovrisi, Greece. The strains were grown as described by Fusco et al. broth and incubated overnight at 30\u00b0C. Two mL of each broth culture were washed in Tris-HCl and resuspended in 500 \u03bcl of the same buffer. Genomic DNA was extracted using the peqGOLD bacterial DNA kit according to the manufacturer's instructions. The integrity, purity, and quantity of DNA were assessed using agarose gel electrophoresis, Nanodrop photometer (Peqlab), and Qubit 3.0 fluorometer (Life Technologies). To prepare sequencing libraries, the Illumina TruSeq Nano DNA LT Library Prep Kit (MiSeq v3-kit) was used according to the manufacturer's instructions, and then sequenced on the Illumina MiSeq platform using the 2 \u00d7 250 pair procedure. Reads were then trimmed with the NxTrim (V2) . The homology-based relationship of Weissella strains toward selected proteins was determined using the BLASTP algorithm on the NCBI site (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Gene models were manually determined, and clustering and orientation were subsequently deduced for the closely linked genes. Genes were also retrieved by keyword search within the UniProtID entry list obtained by functional annotation and then manually curated.Proteins were predicted by using the Prokaryotic Genome Annotation Pipeline , configured as \u201cA la Carte\u201d Mode with Bifidobacterium bifidum ATCC 29521T as an outgroup according to Fusco et al. . The database was searched for preserved domains of all CAZy families, following the protocol proposed by dbCAN was performed by executing a CAZyme annotation using the dbCAN meta server Mapper , obtaining a total of 76, 33, 39, 40, 106, and 26 contigs (>500 bp) for W. beninensis LMG 25373T, W. diestrammenae DSM 27840T, W. fabalis LMG 26217T, W. fabaria LMG 24289T, W. ghanensis DSM 19935T, and W. uvarum B18NM42T, respectively. The mol% GC content ranged from 35.45% (W. beninensis LMG 25373T) to 39.53% (W. ghanensis DSM 19935T), while the assembly length varied from 1,639 Mbp (W. diestrammenae DSM 27840T) to 2,014 Mbp (W. ghanensis DSM 19935T) . The contig N50 values were 57, 163, 166, 143, 54, and 246 kbp for W. beninensis LMG 25373T, W. diestrammenae DSM 27840T, W. fabaria LMG 24289T, W. fabalis LMG 26217T, W. ghanensis DSM 19935T, and W. uvarum B18NM42T, respectively.The genomes of the six 19935T) . The quaWeissella species can be clustered into six different species groups. The first group is constituted by W. thailandensis, W. bombi, W. paramesenteroides, W. hellenica, and W. sagaensis; a second group is formed by W. cibaria (W. kimchii) and W. confusa, which have a 16S rRNA gene sequence identity of 99.3%. The same percentage is shared by W. oryzae and W. muntiaci, which can be placed in a third species group. W. soli occurs close to these couples in the phylogenetic tree and has the highest 16S rRNA gene sequence identity with W. muntiaci (97.35%). W. ceti, W. halotolerans, W. minor, W. uvarum, and W. viridescens are clustered in a fourth species group with an average 16S rRNA gene sequence identity of 95.1%. W. diestrammenae, W. kandleri, W. coleoptorum, and W. koreensis clustered in the fifth group with a shared average 16S rRNA gene sequence identity of 96.8%. W. cryptocerci, W. beninensis, W. ghanensis, W. fabalis, and W. fabaria are located outside this large clade and share an average sequence identity of 96%, with W. fabaria and W. fabalis clustering at a value of 99.41%.The 16S rRNA gene sequence-based phylogeny is shown in W. hellenica and W. sagaensis (89.73%), followed by W. ghanensis and W. fabalis (85.63%), W. beninensis and W. kandleri (68.08%), while W. halotolerans with either W. beninensis (67.29%) or W. ghanensis (67.01%) are the most divergent species within the genus.The ANI analysis results are reported in W. hellenica and W. sagaensis (92.75%), followed by W. hellenica and W. bombi (89.45%). The lowest AAI value was shared between W. muntiaci and W. cryptocerci (51.91%).The matrix of AAI values is shown in W. beninensis, W. kandleri, W. oryzae, W. confusa, W. paramesenteroides, and W. halotolerans species groups. The W. beninensis group includes W. beninensis, W. cryptocerci, W. fabalis, W. fabaria, and W. ghanensis. The W. kandleri group comprises W. kandleri, W. diestrammenae, W. koreensis, W. soli, and W. coleoptorum. The W. oryzae group includes W. oryzae and W. muntiaci. The fourth species group, named the W. confusa species group, comprises W. confusa and W. cibaria. The fifth species group, designated as W. paramestenteroides by Fusco et al. , while the W. muntiaci and W. cibaria type strains have the highest number of GTs (29). Weissella species obtained by analyzing the occurrence and distribution of CAZymes among species.A comparative analysis of CAZy families present in the genomes of W. ghanensis type strain, while 12 were found in the W. beninensis type strain and W. diestrammenae type strain each. One FAD-binding protein with an auxiliary activity family 4 domain that catalyzes the conversion of a wide range of phenolic compounds was identified in the W. ghanensis type strain. Polysaccharide lyase enzymes were retrieved in the genomic sequences of the W. ghanensis, W. fabaria, and W. fabalis type strains. One carbohydrate-binding module CBM34 zyme was retrieved in the genomic sequence of the alpha-glycosidase (GH13_20) of the W. diestrammenae type strain. All strains harbor one N-acetylglucosamine 6-phosphate deacetylase belonging to the carbohydrate esterase of family 9 (CE9), while in the W. diestrammenae type strain, two additional CEs were annotated. Glycosyl transferases were the class with the highest count, with a total of 21 enzymes in the W. ghanensis type strain, 19 in the W. fabaria type strain, 16 in the W. fabalis type strain, 15 in the W. diestrammenae and W. uvarum type strains, and 14 in the W. beninensis type strain.A detailed analysis of the enzymes involved in the metabolism of carbohydrates of the six strains sequenced in this study is reported in W. cryptocerci type strain has the highest enzyme count , while the lowest occurred in the W. kandleri type strain (111).A comparative analysis of carbohydrate metabolism pathways is depicted in W. cibaria, W. cryptocerci, and W. jogaejeotgali type strains showed the highest total feature counts.A comparative analysis of the SEED subsystem is shown in Weissella strains used N-acetyl-D-glucosamine, D-fructose, \u03b1-D-glucose, D-mannose, palatinose, turanose, and maltotriose. Furthermore, according to the comparative analysis of carbohydrate metabolism pathways and the cluster analysis based on carbon source oxidation polymers. Due to the described enzymatic activities, these Weissellas could be employed as starters for the fermentation of such mannose- and oligo mannose-containing vegetables. Their ability to metabolize mannose is corroborated by the fact that in every sequenced genome we retrieved (i) the manXa transporter, which can transfer phosphorus-containing groups to D-mannose, and (ii) the mannose-6-phosphate isomerase [EC:5.3.1.8] for the conversion of D-mannose-6-phosphate to \u03b2-D-fructose 6-phosphate. The mannose transportation operon manXYZ . In the W. uvarum and W. fabaria type strains, the fruAB gene, coding for the D-fructose phosphotransferase, was identified. Only in the W. uvarum type strain can D-fructose enter glycolysis through the subsequent action of the fruK fructokinase and the triosephosphate isomerase, which converts the \u03b2-D-fructose 1,6-bisphosphate to glyceraldehyde 3-phosphate.Except for W. beninensis is the only species able to metabolize D-galactose and raffinose. In fact, the galA gene was detected only in the genomic sequence of the type strain of this species, in addition to two copies of the \u03b2-galactosidase (KAK10_01750 and KAK10_05755). The galA codes for the \u03b1-galactosidase [EC:3.2.1.22] (KAK10_01740), the exoglycosidase that hydrolyzes \u03b1-1,6 galactoside linkages found in sugars, such as raffinose, melibiose, and stachyose, and branched polysaccharides such as galactomannans and galacto-glucomannans. The ability to metabolize nondigestible sugars such as oligosaccharides of the raffinose family and galactomannans is common for several probiotic bacteria a PTS transporter subunit EIIC (KAK10_07455), which transports sucrose into the cell, converting it to sucrose-6-phosphate; (ii) a sucrose-6-phosphate hydrolase (KAK10_07450), which catalyzes the formation of fructose and glucose-6-phosphate; and (iii) a sucrose phosphorylase (KAK10_07625), which reconverts the sucrose-6-phosphate into sucrose. Moreover, a preliminary evaluation of EPS production (data not shown) indicates that W. beninensis can produce ropiness when incubated in MRS added with 20 g/L of sucrose. W. beninensis was isolated from spontaneous fermentation of cassava, and it was previously characterized for the acid production from D-fructose, D-galactose, D-glucose, lactose, maltose, D-mannose, melibiose, D-raffinose, sucrose, N-acetylglucosamine, and D-mannitol foods. To metabolize trehalose, this disaccharide enters the cells throughout the action of the trehalose PTS permease (EC: 2.7.1.201). Consequently, the \u03b1,\u03b1-phosphotrehalase catalyzes the hydrolysis of \u03b1,\u03b1-trehalose 6-phosphate into D-glucose and D-glucose 6-phosphate. This enzyme was annotated in the genomic sequences of the W. fabalis, W. fabaria, and W. ghanensis type strains to occur in a genomic cluster, which shows differences in the organization among these species . Common to all 3, within the cluster, there are (1) a gene coding for a hypothetical protein with a GH (family 13) catalytic domain, (2) the treR gene , (3) the treC gene , (4) the genes coding for TreB subunit EIIC and IIA), (5) one flippase gene, (6) one gene coding for an EpsG family protein, (7) one for a sugar transferase, and (8) several genes coding for glycosyl transferases. In the W. fabaria type strain, this locus also comprises a sequence of 14 kbp downstream of treR, where there are annotated rhamnose operon rbf ABCD and genes coding for (1) a dTMP kinase, (2) a LicD family protein, (3) a DUF1972 domain-containing protein, (4) a CpsD/CapB family tyrosine-protein kinase, (5) a capsular biosynthesis protein, (6) an LCP family protein, and (7) a tyrosine phosphatase. The trehalose operon has not yet been described in the Weissella species. In addition to the treR and treB genes, Lactococcus lactis includes the phosphomannomutase gene femB, the trehalose/maltose hydrolase gene trePP, and the \u03b2-phosphoglucomutase pgmB gene , within a locus comprising genes coding for the transcriptional regulator LacI, an \u03b1-glycosidase, a glycoside hydrolase, a galactose maturotase, and sugar transporters.Trehalose, or \u03b1-D-glucopyranosyl-1,1-\u03b1-D-glucopyranoside, is a disaccharide made up of two \u03b1-D-glucose molecules joined by an \u03b1-1,1 glycosidic bond. It naturally occurs in bacteria, fungi, yeasts, algae, plants, and invertebrates, including insects, but it is absent in vertebrates. Its major dietary sources are mushrooms; in fact, it is contained in most edible fungi and is an important part of reconstituting dried shiitake mushrooms. For this reason, it is also referred to as a mushroom sugar, while it is called seaweed sugar in China since trehalose is contained in marine plants such as \u201chijiki\u201d seaweed. species , while tL. lactis by Andersson and R\u00e5dstr\u00f6m , W. beninensis (KAK10_00105), and W. uvarum (KAR63_02130) type strains. The mapA gene, which codes for the maltose phosphorylase [EC:2.4.1.8] that catalyzes the reaction between maltose and phosphate to form D-glucose and \u03b2-D-glucose-1-phosphate, was found to be present in the W. uvarum (KAR63_02125), W. beninensis (KAK10_00115), and W. diestrammenae (KAR27_07545) type strains. In contrast to L. lactis, the malP and pgmB genes are located closely on the genomic sequences of the species in which they were annotated. In the W. uvarum type strain, this operon also contains genes coding for the glucose transport system, formed by the PTS transporter subunit EIIC and PTS glucose transporter subunit IIA, and a trehalose operon repressor. However, the sequences surrounding this genomic area are different from the trehalose operon as above described in the other Weissella species, indicating a divergent evolutionary pattern. In the pgmB genomic locus of the W. diestrammenae type strain, there are also genes coding for a galactose mutarotase, a glycosyl hydrolase, the \u03b1-glycosidase (KAR27_07540) gene, a gene coding for an MFS transporter, one for a LacI family DNA-binding transcriptional regulator, one for an ECF transporter, one for an ABC transporter substrate-binding protein, and a permease gene. The pgmB gene codes for a \u03b2-phosphoglucomutase, which catalyzes the interconversion of D-glucose 1-phosphate (G1P) and D-glucose-6-phosphate (G6P), forming \u03b2-D-glucose 1,6-(bis)phosphate (\u03b2-G16P) as an intermediate. It is the catabolic activity in the maltose and trehalose pathways. Although pgmB has not yet been characterized in the Weissella species, this gene was reported as essential in the trehalose pathway of L. lactis that catalyzes maltose hydrolysis to produce two molecules of D-glucose.The maltose operon was first described in R\u00e5dstr\u00f6m . MaltoseW. fabalis, W. ghanensis, and W. uvarum type strains. The substrates for this hydrolytic enzyme are maltooligosaccharides, phenyl \u03b1-maltoside, nigerose, soluble starch, amylose, amylopectin, and \u03b2-limit dextrins glycosidic linkages in homogalacturonan. The capability of these species to hydrolyze pectin suggested by the presence of these enzymes could be relevant for the exploitation in the food industry; pectin lyases are, in fact, usually employed in wine and juice prepress maceration, as well as in juice clarification methods can be found in the article/VF conceived the work and interpreted the data. G-SC performed the genomic sequencing. VF and FF organized and performed the bioinformatic work. DC checked the purity of the strains and prepared the working cultures for DNA extraction and phenotypic characterization. MM performed the phenotypic characterization. VF, FF, and MM wrote the manuscript. All authors contributed to the revision of the manuscript, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Dear Editor,Solanum habrochaites and S. galapagense have been widely used as germplasm donors in modern breeding to improve biotic and abiotic stress tolerance of tomato. S. habrochaites grows in the Peruvian Andes at altitudes up to 3300\u00a0m and is notable for its tolerance of chilling and drought and resistance to many diseases and pests. S. galapagense is endemic to the Gal\u00e1pagos Islands, has extraordinary salt tolerance and insect resistance, and appears even more closely related to the cultivated tomato (Solanum lycopersicum) than Solanum pimpinellifolium, the wild progenitor of cultivated tomato [Introducing beneficial genes/alleles from wild relatives into the cultivated tomato has been an important approach for tomato breeding. d tomato . Due to d tomato or PacBiS. habrochaites (accession LA0407) and S. galapagense (accession LA0317) were developed using PacBio HiFi reads and chromatin interaction maps generated with Hi-C technology. The final assemblies of S. habrochaites and S. galapagense had total contig sizes of 950.7 and 859.9\u00a0Mb, respectively, and contig N50 sizes of 6.74 and 12.32\u00a0Mb, with 95.4 and 94.4% of the contigs anchored and ordered on the 12 chromosomes assembly index (LAI) scores of 13.50 and 13.35. Moreover, the consensus quality values (QVs) of S. habrochaites and S. galapagense assemblies were 42.91 and 44.28, respectively, corresponding to a base accuracy of 99.995 and 99.996%. Taken together, the results indicated the high degree of contiguity, completeness, and base accuracy of these two genome assemblies.In this study, chromosome-scale assemblies of omosomes . The S. S. habrochaites and S. galapagense genomes harbored 74.2% (705.2\u00a0Mb) and 73.2% (632.2\u00a0Mb) repetitive sequences, respectively, of which LTR retrotransposons accounted for 58.8 and 59.0% , and S. galapagense and S. lycopersicum diverged around 0.62\u00a0Mya. A total of 16\u2009666 gene families were shared among S. habrochaites, S. galapagense, S. lycopersicum, S. pimpinellifolium, and S. pennellii, and 366 and 190 were unique to S. habrochaites and S. galapagense, respectively , according to the pipeline described in our previous study [S. habrochaites and S. lycopersicum and 98\u2009443 SVs with a total length of 62.2\u00a0Mb between S. galapagense and S. lycopersicum were identified homologous to Arabidopsis rare cold-inducible protein 3 (RIC3) [Solyc07g049240) in SL4.0 relative to cultivated tomato, genome sequences of us study . A totalentified . The insses etc. . Coding ism etc. . These rreatment , includiin SL4.0 . The uprS. habrochaites were enriched in the terpenoid biosynthetic process. Terpenoids play roles in plant defense against pathogens and pests. Terpene synthases (TPSs) are key enzymes in generating terpenoids. A total of 59, 50, 43, 36, and 41 TPS genes were identified in genomes of S. habrochaites, S. galapagense, S. lycopersicum, S. pimpinellifolium (LA2093), and S. pennellii (LA0716), respectively has been proposed in S. habrochaites [SBS and zFPS had similar expression levels in the seven S. habrochaites accessions, except LA1352, suggesting both conserved and diverged sesquiterpene biosynthesis in these accessions , 831 nucleotide binding site (NBS)-encoding proteins and 391 receptor-like proteins (RLPs) . Gene fapersicum . In addiS. habrochaites and S. galapagense provide robust references, in particular, new gene sources of stress tolerance and terpene biosynthesis for functional genomic research and genetic improvement in tomato.In summary, the high-quality genome assemblies of This work was supported by grants from the National Natural Science Foundation of China (32170395), the US National Science Foundation (IOS-1855585), the Foundations of Hubei Hongshan Laboratory (2021hszd017), and the Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences.L.G., Z.F., X.Y., and S.G conceived the project. Y.S., M.Q., S.G., and C.H. performed the experiments. X.Y. and M.Q. analyzed the data and wrote the manuscript. L.G., Z.F., and S.G revised the manuscript.Raw sequencing data and genome assemblies have been deposited in the Genome Sequence Archive (GSA) under the BioProject accession number PRJCA008297.The authors declare no conflicts of interest.Horticulture Research online.Web_Material_uhac139Click here for additional data file."} +{"text": "Modern life, especially in large cities, exposes people to a high level of noise, high density of population, disrupted sleeping, large amount of excessive and controversial information as well as to other negative factors; all this may cause chronic psycho-emotional stress. The latest publications often use the term \u201cSyndrome of megalopolis\u201d, which means disruption of sleeping, high anxiety, and altered reproductive function. Medical treatment of infertility may also be considered as a stress factor, especially when infertility lasts for years and is aggravated with emotional frustration. Long-lasting distress may worsen health in general and suppress reproductive function, in particular. The review presents the data on the effects of maternal stress on folliculogenesis, especially when assisted reproductive technologies (ARTs) are used. Clinical data are presented alongside data from laboratory animal experiments. Different maternal stress models are taken into account in respect of their inf luence on oocyte maturation and embryo development. The interfering of psycho-emotional stress and reproductive function is the focus of the review. In these situations, exogenous hormones compensate for the stress-related disruption of the hypothalamic-pituitary-gonadal axis. When ARTs are implemented, stress-induced disruption of oogenesis is realized not via a decrease in hypothalamic and pituitary hormones, but by other ways, which involve paracrine mechanisms described in this review. Based on the literature analysis, one may conclude that stress negatively affects oocyte maturation in the ovary and suppresses subsequent embryo development. The role of some ovarian paracrine factors, such as BDNF, GDF-9, HB-EGF, TNF-\u03b1, and some others has been elucidated Adult reproductive function and children\u2019s health are infocus of scientific interest and of a great public concern.The implementation of assisted reproductive technologies(ARTs) into clinical practice helps to overcome manytypes of infertility, miscarriage, and to prevent monogenicdiseases in children. At the same time, patients in ARTclinics often report that the infertility itself as well as itstreatment is the traumatic experience, which may lead tothe anxiety and even depression . Thus, chronic psycho-emotionalstress that affects both women and men during infertilitytreatment and implementation of the ART in particular, aresignificant factors affecting fertility.There are numeric evidences of the negative impact ofchronic stress on the human well-being, on the mammalianphysiology in general, and on the reproductive functionin particular . The effects of maternal stress during pregnancy onthe body weight of newborns and on the neurodevelopmentin children are reported; moreover, there are evidences thatprenatal stress affects the behavior and other phenotypiccharacteristics of different animals .Although the effects of psycho-emotional stress aredescribed in the medical literature and on the laboratoryanimal models, these two areas of research are mostlydeveloping independently. It should be noted, that nowadaysART is widely used in medical practice, thus theeffects of psycho-emotional stress on reproduction, inclu-ding stress arising from the use of ART, as well as studyingthe mechanisms underlying these effects are of greatconcern. The objective of this article is to review andto systematize the accumulated experimental and clinicaldata describing the effects of chronic psycho-emotionalstress on gametogenesis, fertility, ART outcomes, and theoffspring health; to review animal models used in suchexperiments and to outline possible ways aiming to mitigatethe adverse effects of stress associated with the useof ARTs. At the same time, experimental data obtained onanimal models are compared with clinical observationspublished in the medical literature. The effects of stresson folliculogenesis and embryogenesis, as well as on theART-born offspring, both in humans and in experimentalanimals, are analyzed.In experimental studies aimed to elucidate the effectsof chronic psycho-emotional stress, including the stressassociated with the use of ARTs, on the development ofoocytes and early embryos, animal model of restrictionstress , the predatorexposure model ,or the model of chronic unpredictable mild stress \u2013 CUMS are mostfrequently used. Plasma levels of corticosteroids, adrenocorticotropichormone, corticotropin-releasing hormone,adrenaline, noradrenaline, and ghrelin are normally measuredin such studies as stress indicators; less often stressinducedanalgesia, behavioral characteristics are also takeninto accountThe restriction model of stress is one of the most popular. Sometimes the experimental animalis fixed with tapes, plaster, cloth towel, or other means sothat only the head can move freely; however, most oftenfor this purpose animal is settled in a plastic or metal tube,or a special microcell restricting its movements . The duration of the procedureand the number of restriction episodes affect the intensityof the stress response and should be taken into account.Predator model of psychogenic stress is also widely used,for this purpose the natural predators of mice such as cats,ferrets, rats or foxes are normally chosen; sometimes not thepredator itself, but its smell is offered to the tested mouse,this causes the fear and anxiety in the experimental animal. Themost commonly used version of the predator stress modelfor mice is the presentation of a hungry cat or its scentwithout physical contact between the mouse and the cat. The presence of the cat affects the stressedanimal, and activating its hypothalamic-pituitary-adrenalaxis, therefore triggering the secretion of glucocorticoids.Another widely used model is CUMS. Rodents are presentedwith constantly changing variable stressors over severalweeks . According to this model,combination of isolation and overcrowding can be used asstressors, as well as unpredictable changing the situation in the cage: wet sawdust, tilting the cage, disruption of theday-night cycle, exposure to different temperatures, the useof mobility restrictions, social stress . After several days of CUMS regimen, animalsshow an increase in blood corticosterone levels anda reduced response to pleasurable stimuli .Animal studies demonstrate that psycho-emotional stressexperienced by the female affects the quantity and qualityof oocytes, which in turn contributes to further embryonicdevelopment (see the Table). Many studies come to theconclusion that stress leads to a decrease in the developmentalpotential of oocytes ; this, in turn, resulted in areduced percentage of blastocysts developed from suchoocytes. A decrease in the developmental potential ofoocytes was associated with the duration and severity ofthe applied stress treatment . It was alsorevealed, that antral follicles are more sensitive to stressthan preantral ones . Moreover, chronicunpredictable stress disrupts ovulation and cyclicity in femalemice, these changes in reproductive system correlatewith high levels of corticosteroids in the blood and withthe increased activity of superoxide dismutase; moreover,after hormonally induced stimulation of superovulation,mature oocytes were not found in the stressed female mice.Stress can also affect embryo implantation. It was shownthat even a short restriction stress lasting 24 hours, butcoinciding in time with the \u201cimplantation window\u201d on thefourth day after mating, negatively affects implantation inmice and slows down the onset of hatching in blastocysts. This effect was mediated througha decrease in the blood levels of progesterone and estradiol,and was associated with the level of expression of heparinbindingepidermal growth factor both in the uterus and inthe blastocysts .It is known that stress leads to activation of the hypothalamic-pituitary-adrenal and sympathoadrenal systems;therefore, traditional markers of stress are glucocorticoidsand adrenaline. Restriction stress in mice was shown tobe accompanied by an increase in plasma cortisol levels. Cortisol injections also led to suppressionin oocyte development. In addition, stress led to a decreasein the follicle-stimulating hormone (FSH) release,while injections of cortisol did not cause this effect. Theresearchers concluded that cortisol affects oocytes througha direct effect on the ovary, while stress impairs theircompetence indirectly, via effects on the hypothalamicpituitary-adrenal and hypothalamic-pituitary-ovarian axes.One of the ways to implement stressful effects on thefemale reproductive system is to influence the production ofovarian regulators of folliculogenesis, including those mediatedby corticotropin-releasing hormone. Corticotropinreleasinghormone (CRH), which is identified in the thecaand stroma of the ovaries, as well as in the cytoplasm ofoocytes and granulosa cells, is involved in the regulationof follicular maturation, ovulation, the formation of corpusluteum, and the synthesis of the ovarian steroid hormones.In female mice, restriction stress caused an increase ofCRH concentration in blood serum, ovaries, and oocytes,as well as an increase in the expression of the CRH receptor1 (CRHR1) in granulosa and theca cells, but a decreasein the expression of the glucocorticoid receptor and brainderivedneurotrophic factor (BDNF) in the ovaries . All this ultimately led to an imbalance betweenestradiol and progesterone concentration in blood and negativelyaffected the developmental competence of oocytes.Besides, the addition of CRH to the culture medium duringoocyte\u2019s in vitro maturation disrupted its development andincreased the rate of apoptosis in granulosa cells . In another study, it was shown that a stressinducedincrease of CRH both in blood and in the ovariesof female mice triggers apoptosis in oocytes and in ovariangranulosa cells due to the activation of the TNF-\u03b1 system,which results in impaired oocyte competence .Animal experiments using CUMS stress model demonstratedthat inhibition of follicle development is associatednot only with gonadotropins, but also with growth factorssuch as growth differentiation factor 9 (GDF-9) and BDNF. Exposure of female mice to CUMSresulted in the suppressed follicular development, increasedlevel of follicular atresia, and downregulated GDF-9 expression.The introduction of exogenous gonadotropinspartially mitigated these negative effects and restored thedevelopment of antral follicles, which was suppresseddue to chronic stress, but these exogenous gonadotropinsexerted no effects on secondary follicles. However, theintroduction of recombinant GDF-9 restored the developmentof secondary follicles. Co-administration of GDF-9and gonadotropins in stressed mice restored both secondaryand antral follicles. Another study of the same researchgroup showed that CUMS reduces BDNF expression inantral follicles but does not affect BDNF expression inprimordial, primary, and secondary follicles . Chronic unpredictable mild stress also reducedthe number of retrieved oocytes and the percentageof blastocysts formed, which was corrected by the use ofexogenous BDNFSome studies attempt to elucidate mechanisms of theinfluence of psycho-emotional stress on the developmentalpotential of oocytes and preimplantation embryos. Onestudy reported, that the transition of the heterochromatinconfiguration from the non-surrounded nucleolus (NSN)type to the surrounded nucleolus (SN) type is suppressedat the germinal vesicle (GV) stage preovulatory oocytesexposed to restriction stress, thus, the developmentalpotential of such oocytes is impaired .Besides, psycho-emotional stress can lead to disruptionof meiotic division in oocytes. It was shown that in stressedfemales, the proportion of aneuploidy in mature oocytes increases,and the percentage of aneuploid oocytes was threetimes higher in oocytes with accelerated maturation comparedto the delayed ones .The authorsconcluded that maternal stress may cause oxidative stresswithin oocytes and impair spindle assembly by inactivatingthe spindle-assembly checkpoint .In addition to hormonal imbalance, psychosocial stresscauses an increase in the formation of reactive oxygenspecies (ROS). High levels of ROS cause oxidative stress,which leads to meiotic cell cycle arrest and resulted inapoptosis . Thisconclusion was further supported by the observation thatoxidative stress induces granulosa cell apoptosis and leadsto a decrease in estradiol levels, ovulation frequency, andoocyte quality . Besides, oxidativestress-induced apoptosis of granulosa cells caused the impairmentsof the contacts of these cells with oocytes, whichdirectly affects the supply of nutrients and the availabilityof growth factors that affect the quality of oocytes in preovulatoryovarian follicles . In experimentsusing the restriction stress model, it was shown thatstress caused the accumulation of ROS in the blood serumof mice, ovaries, and oocytes, and also caused a decreasein the percentage of blastocysts developing in vitro withfewer cells observed in these blastocysts .It should be noted that the mechanism of the negative impactof chronic stress on the ovary through inhibition of therelease of gonadotropins has been well studied. While otherovarian regulatory mechanisms involved in this process arenot yet understood. Elucidating these paracrine mechanismsmediating the effects of stress on oogenesis and, subsequently,on the development of embryos is important formore effective use of medical reproductive technologiesin patients experiencing chronic psycho-emotional stress.Clinical data without ARTFunctional hypothalamic amenorrhea which may be diagnosedin the absence of menstruation for three or moremonths represents the most striking clinical manifestationof stress-induced disorders of folliculogenesis, with initiallyintact menstrual function . First of all,functional hypothalamic amenorrhea is characterized by adecrease in the frequency and amplitude of gonadotropinreleasinghormone release peaks, what leads to a decrease inthe production of FSH and luteinizing hormone (LH) by thepituitary gland and, as a result, to the absence of hormonedependentfollicle growth. This leads to a disruption ofthe transition from secondary follicles to antral follicles,a disruption of the formation of a pool of growing follicles,the absence of a dominant follicle and, accordingly, lackof the corpus luteum. Therefore, functional hypothalamicamenorrhea is characterized by a decrease in the productionof estradiol in the ovaries, which is accompanied bythe absence of uterine endometrial proliferation and theabsence of menstruation .Manifestations of other disorders of folliculogenesiscaused by stress may not be as pronounced as amenorrhea.Subclinical manifestations include lengthening andirregularity of the menstrual cycle, insufficiency of theluteal phase of the cycle, luteinization of the non-ovulatedfollicles , as well as the absence of a mature oocytes in the ovulatedfollicle . In the case of subclinicalmanifestations, there is also a decrease in the productionof gonadotropin-releasing hormone, however, FSH stillreaches a level sufficient to initiate follicle growth. In thiscase, the growth of the follicles may be slow, with the prolongationof the first phase of the cycle, the late ovulation,and the reduced production of estradiol, which can lead toendometrial hypoplasia . Changes in gonadotropin-releasing hormone pulsationalso affect the intensity and frequency of LH peaks,although serum LH levels may remain normal or be onlyslightly reduced . Deficiency inthe production of gonadotropin-releasing hormone andestradiol can lead to a reduced LH peak in the preovulatoryperiod and to luteinization of the unovulated follicle, theformation of ovarian cysts, luteal phase insufficiency, andthe reduced progesterone production in the second phaseof the cycle . Besides, chronic stressis characterized by increased secretion of cortisol mainlyat night, with normal levels of daily and morning secretion, which also contributes to a decrease inthe amplitude or even the absence of the ovulatory peakof gonadotropins .Certainly, not all women demonstrate disruption of folliculogenesisand the distortion of the menstrual cycle inthe stressful situations . There are both physiological and psychologicalfactors determining tolerance to stress-induced ovariandysfunction . Factors that protect the reproductive systemin the situation of stress operate at the level of the centralnervous system (the stressor is not perceived), at the level ofthe hypothalamic-pituitary-adrenal system (impaired secretionof glucocorticoids), at the level of the hypothalamicpituitary-gonadal system (resistance of the gonads to theaction of glucocorticoids), and protection from the actionof glucocorticosteroids with the help of a proteins that bindsteroids .The development of hypothalamic amenorrhea leads tothe reproductive failure due to the absence of folliculargrowth and the lack of matured oocytes, as well as the lackof appropriate preparation of the endometrium. Sometimesin the case of stressful influences with the formation of luteinizationof the unovulated follicle and a deficiency of theluteal phase, the absence of menstruation (amenorrhea) isnot observed, but the reproductive potential is significantlyreduced . Such alterations can be corrected by the proscription of appropriate medical treatmentthat compensate the deficiency of pituitary and/or steroidhormones. However, there is the problem of infertility ofunknown origin, with unimpaired folliculogenesis andovulation. A more detailed study of oogenesis becamepossible with the introduction of ART.There are several evidences of a high rate of earlypregnancy loss, not associated with chromosomal abnormalities,or an increased anxiety and depression in womenwith a history of miscarriages. Pregnancy loss itself maybe considered as a powerful stressor, which can lead to therecurrent miscarriage . Early pregnancy loss indicates a low viability ofthe embryo or lack of its interaction with the uterus afterimplantation, which is probably the result of gametogenesisdisruption, distortion in preparation of the endometriumfor pregnancy or the development of immunologicalincompatibility between the maternal organism and theembryo. All of these conditions have been described aspossible consequences of stress experienced by a womanduring conception and early pregnancy . These phenomena can lead toimpaired placentation and the development of pregnancycomplications typical for later stages of gestation, such asfetoplacental insufficiency, preeclampsia, preterm birth;these conditions may affect the health of children born. Mechanismswhich cause a change in ovarion function under stress areshown in the Figure.The use of gonadotropins to induce the growth of severalfollicles for controlled ovarian hyperstimulation is oneof the core ARTs. Thus the stress-induced deficiency ofCRH, FSH, and LH, which was discussed in the previoussection, is compensated by the administration of exogenousgonadotropins. Moreover, current protocols for controlledovarian hyperstimulation involve blockade of endogenousgonadotropin-releasing hormone production in order toprevent premature ovulation. Taking all this into account, itcan be concluded that during the use of ART, stress-induceddisturbance of oogenesis is realized not through a decreasein the production of hormones of the hypothalamus andthe pituitary gland, but via other paracrine and autocrinemechanisms described above.Many reproductologists noticed that unsuccessful ARTattempts pretty often take place during adverse life events,such as death of a relative, family problems, etc. This isin practice described by reproductologists as cases of \u201cinexplicablylow\u201d quality/quantity of oocytes and embryosin ART programs with an initially good prognosis, and\u201cunexplained\u201d improvement in the quality/quantity ofoocytes and embryos in repeated attempts using the sameprotocols when life situation of the patient was improved. A possible explanationfor such observations is the inhibitory effect of thestress on gametogenesis.Data from clinical studies in humans are contradictory.A significant part of these studies indicates the depressingeffect of psychological stress on the results of ART. Thus,in a study by Ebessen et al. (2009) involving 809 womenpracticing ART for the first time, a decrease in the numberof received oocytes, embryo quality and pregnancy rate wasshown with an increase in the number of adverse life eventsthat reduce the quality of life, as well as with an increasein the level of perceived stress one month before infertility treatment with ART . Another studyshowed the effect of initial stress on the number of oocytesretrieved and fertilized, as well as on pregnancy and livebirth rates . Li et al. (2011)found that initial psychological stress was negatively associatedwith pregnancy rates in ART programs, but intrafollicularconcentrations of norepinephrine did not differbetween the pregnant and non-pregnant women. In anotherstudy, the association of ART results with anxiety levelsand serum concentrations of cortisol and noradrenaline wasinvestigated. Elevated levels of cortisol and norepinephrinehave been shown to be associated with anxiety levels andnegatively correlated with pregnancy and live birth rates.A more recent paper published the results of a study with135 women involved, that examined the association of salivaryand hair cortisol with ART outcomes . It was shown that salivary cortisol levels were notpredictive of ART outcomes. Whereas, lower hair cortisolconcentrations predicted the high probability of pregnancy.A recent study of 304 women found that more than 80 %of respondents had elevated levels of anxiety and depression,and these symptoms were inversely correlated withthe success of ART implementation .At the same time, some studies do not show an associationbetween anxiety levels, as well as salivary and serumcortisol levels and reproductive outcomes in ART patients. Miller et al. (2019)assessed the level of anxiety using the Perceived StressScale, salivary cortisol concentration at the beginning ofthe ART cycle, on the day of follicle puncture, and on theday of embryo transfer, and also measured the level ofcortisol in the follicular fluid. The authors noted an increasein cortisol and anxiety on the day of follicle puncture, butdid not find an association of these stress indicators withpregnancy rates. Besides, elevated follicular cortisol levelscorrelated with positive ART outcomes. In vitro fertilization(IVF) failure has also been shown to predict subsequentpsychological distress, but pre-IVF psychological distressdid not predict IVF failure . The level ofstress and the number of oocytes obtained in ART programsfor the treatment of infertility was compared. The resultsof this study showed a significantly higher level of stressin patients with infertility, but the number of oocytes wascomparable in both groups .It can be concluded that despite the large number of publicationsaddressing the effects of stress on the effectivenessof ART in humans, the data obtained are very contradictory.In these studies not only sizes of study groups are variable,but also different approaches to assess experiencedstress and anxiety were used. Moreover, many of thesestudies suffer from the lack of randomization. The majorityof these studies do not take into account the fact thatthe patient\u2019s knowledge of his prognosis can significantlyaffect the assessment of the level of chronic stress and theresults of the questionnaire. Due to the heterogeneity ofthe published data, the conclusions of these works are also contradictory. Most authors are careful in conclusions aboutthe relationship between stress and reproductive function,based both on the data of their studies and on the generalbiological considerations suggesting the impossibility ofcomplete suppression of the reproductive function duringunfavorable periods due to the need for the survival of thespecies .The availability of data indicating a significant impactof psychosocial stress on the reproductive system hascontributed to an increase in research aimed at studyingpsychotherapeutic effects in the treatment of infertility.An early paper addressing this issue highlights the urgentneed for quality-compliant research feasible for evaluation. The author analyzed 38 studies, 25 of whichwere classified as independent, and only eight of them metthe research quality standards. In summary, three out ofeight good quality studies showed higher pregnancy ratesin the psychosocial intervention group compared to theroutine care group . In another paper, a metaanalysisof 22 studies was conducted, which indicates thatpsychotherapy reducedanxiety and depression in infertile patients and possiblyaffected the success rate of conception .A review by Campagne (2006) recommends planning ofinfertility medication taking into account the level of stress,and suggests stress-reducing therapies, prior to initiatinginfertility treatment .Subsequent studies presented conflicting results of theuse of psychological techniques. H\u00e4mmerli et al. (2009)included 21 controlled trials in their meta-analysis and concludedthat psychological interventions were not associatedwith any significant changes in psychological status, buthad a positive effect on pregnancy rates in patients receivingtreatment without ART . Theyalso concluded that a therapy of six or more sessions wasmore effective than a shorter duration of therapy. Frederiksenet al. (2015) performed a meta-analysis of 39 originalarticles and reported that women receiving some form ofpsychotherapeutic intervention were about twice as likely tobecome pregnant compared with women receiving standardtreatment .Ying et al. (2016) included 20 randomized trials in theirsystematic review. They concluded that there were methodologicalproblems with studies that reported significanteffects of psychological stress on the pregnancy rates,and recommended that a more thorough investigation tobe conducted, especially for the most stressful period forinfertile patients, in particular, during the time of waitingfor the results of a pregnancy test. In a systematic reviewby Gaitzsch et al. (2020), only two of six studies showeda significant positive effect of psychological interventionson the fertility . At the same time,a meta-analysis including 15 studies showed a positive association between psychosocial interventions, especiallylong-term ones, and pregnancy rates in infertile women andcouples receiving ART treatment .Thus, many researchers emphasize the presence ofmethodological and practical questions to the currentlyaccumulated data. There is a need for more studies andfor unified programs of psychological help. The positiveeffects of psychotherapy demonstrated in some of thestudies indicate that this is a promising area for furtherresearch.The identification of chronic psycho-emotional stress ischallenging both in humans and in experimental studieswith laboratory animals. The psychological tests andquestionnaires in humans are considered as the \u201cgoldstandard\u201d for such psycho-emotional stress identifying,however, it requires a lot of time, may not reflect thereal physiological situation due to subjective distortionsintroduced by the interviewee . It is also important that theuse of psychological tests and questionnaires is not possiblein experiments with laboratory animals. Therefore, thesearch for reliable biomarkers of chronic psycho-emotionalstress which can be objectively measured and evaluated isextremely important.The use of animal models helps to understand themechanisms underlying the impact of assisted reproductivetechnology accompanied by stress on the female reproductivefunction and on the offspring health. Analysisof the literature let to conclude that stress negativelyaffects the development of ovarian oocytes, as well asthe subsequent embryo development. The role of someovarian paracrine factors that are involved in theseprocesses has been revealed in these studies. Meanwhile,additional experiments on the effect of psycho-emotionalstress on the results of in vitro fertilization and embryotransfer experiments are warranted, since clinical dataare contradictory and only a few experimental works onlaboratory animals are available so far.Available data on the laboratory animals show theeffectiveness for the use of such factors as GDF-9and BDNF to reduce the inhibitory effect of stress onfolliculogenesis and embryo development, these factorsare promising to be used in the reproductive medicine.Moreover, psychotherapeutic techniques which alleviateeffects of stress may increase resistance to stress at the levelof the central nervous system, i. e. influence the perceptionof a stressful event or stimulus. There are reports confirmingthe effectiveness of psychological techniques in reducingpsychological stress, and there are evidences that the useof these techniques is associated with a significant increasein pregnancy rates . 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DOI 10.1095/biolreprod.111.095281."} +{"text": "Over the past 20 years, coronaviruses have caused three epidemics: SARS-CoV, MERS-CoV, and SARS-CoV2, with the f irst two having a very high lethality of about 10 and 26 %, respectively. The last outbreak of coronavirus infection caused by SARS-CoV2 in 2019 in China has swept the entire planet and is still spreading. The source of these viruses in humans are animals: bats, Himalayan civets, and camels. The genomes of MERS-CoV, SARS-CoV and SARS-CoV2 are highly similar. It has been established that coronavirus infection (SARS-CoV and SARS-CoV2) occurs through the viral protein S interaction with the lung epithelium \u2013 angiotensin-converting enzyme receptor 2 (ACE2) \u2013 due to which the virus enters the cells. The most attractive model for studying the development of these diseases is a laboratory mouse, which, however, is resistant to coronavirus infection. The resistance is explained by the difference in the amino acid composition of mouse Ace2 and human ACE2 proteins. Therefore, to create mice susceptible to SARS- CoV and SARS-CoV2 coronaviruses, the human ACE2 gene is transferred into their genome. The exogenous DNA of the constructs is inserted into the recipient genome randomly and with a varying number of copies. Based on this technology, lines of transgenic mice susceptible to intranasal coronavirus infection have been created. In addition, the use of the technology of targeted genome modif ication using CRISPR/Cas9 made it possible to create lines of transgenic animals with the insertion of the human ACE2 gene under the control of the endogenous murine Ace2gene promoter. This \u201chumanization\u201d of the Ace2 gene makes it possible to obtain animals susceptible to infection withcoronaviruses. Thus, transgenic animals that simulate coronavirus infections and are potential platforms for testingvaccines have now been created The viral infection that caused severe acute respiratory syndrome(SARS) was first recorded in December 2019 in Wuhan,China, and rapidly spread around the world on a pandemicscale .Soon, at the end of January 2020, it was published that thecausative agent of the disease is a new type of coronavirusisolated from the bronchoalveolar secretions of six patientsand called 2019-nCov . Later, on the recommendationof the WHO , thedisease caused by the new SARS-CoV-2 virus was calledCOVID-19. Almost simultaneously (in early February 2020),additional data on the novel coronavirus infection from sevenpatients, six of whom were seafood vendors in the Wuhanmarket, were published . According toP. Zhou et al. (2020), the SARS-CoV-2 virus genome shares85 % similarity with the bat coronavirus and 79.6 % similaritywith the previously described human SARS-CoV.Model animals are an important tool in the research ofmany human pathologies. However, the creation of adequateanimal models of infectious diseases has specifics associatedwith the high rate of co-evolution of the host-parasite system,during which both participants gain many specific adaptations.An example of this is the tropism of infectious humanviruses based on the specific interaction of viral proteins withcellular receptor proteins, which gives rise to infection. Theabsence of the specific binding of viral proteins and targetcell proteins causes resistance to a specific viral infection indifferent species.On the other hand, differences in the response of the immunesystem to a particular viral agent in humans and animalscan also become an insurmountable obstacle to the useof animals as model objects. Despite these difficulties, manymouse models of human viral diseases have been created, which makes it possibleto study the fundamental aspects of the development of aparticular disease, such as infection processes, the course of aviral disease, and the interaction of the virus and the immunesystem. Such models have proven to be highly demandedfor preclinical trials of new vaccines and antivirals .This review is devoted to the creation of laboratory micesusceptible to the SARS-CoV-2 and SARS-CoV coronavirusesin order to create an experimental platform for studying boththe coronavirus pathogenesis itself and testing pharmacologicalantiviral drugs and vaccines.The group of coronaviruses (CoVs) is represented by largeenveloped viruses, the genome of which consists of singlestrandedRNA . Coronaviruses are membersof the subfamily Coronavirinae, family Coronaviridae, orderNidovirales. CoVs are composed of four genera: alpha-, beta-,gamma-, and deltacoronaviruses , all ofwhich cause zoonotic infections in animals. In the past twodecades, of the entire cohort of coronaviruses, two have becomepathogenic to humans, causing SARS and Middle Eastrespiratory syndrome (MERS). In the first case, the outbreakoriginated in Guangzhou province in China in December2002 and then spread to five continents .According to the WHO, the SARS-CoV epidemic affected8437 people, 813 of whom died. MERS-CoV coronavirusinfection outbreak originated in the Arabian Peninsula in 2012 and spread to the Middle East, England andSouth Korea. According to the WHO, the epidemic affected1728 people, with 624 cases of MERS-CoV infection resultingin death. It has been established that animals are the sourceof human infection with SARS-CoV and MERS-CoV (moredetails below).To enter human target cells, SARS-CoV and MERS-CoV usetheir \u201ccrown\u201d, which is represented by many spike-shaped (S)proteins. It has been established that the SARS-CoV S proteininteracts with angiotensin-converting enzyme 2 as an entry receptor . During viral infection, the trimeric S proteinis cleaved into S1 and S2 subunits, after which they are recognizedby human cell receptors .Further, the S1 subunit containing the receptor-binding domainbinds directly to the peptidase domain of the ACE2 protein,while S2 is responsible for membrane fusion .Based on this knowledge, several independent groupsof researchers have proposed that the new SARS-CoV-2coronavirus uses the same mode of entry into human cellsas previously described SARS-like viruses. To confirm thishypothesis, comparisons were made between the protein sequencesof SARS-like viruses and the new coronavirus SARSCoV-2, and a high level of similarity was revealed. Further,to establish binding sites, a crystallographic analysis of thecomplex between the S1 subunit of the coronavirus and thehuman ACE2 protein was performed. As a result, it was found that the ACE2 protein has five key amino acid sequences thatare involved in the binding of the S1 subunit of the virus .The ACE2 gene in humans is expressed in the lungs, arteries,heart, brain, and small intestine and is an important componentof the renin-angiotensin-aldosterone system . Expression of ACE2 in the lungs is mainly limited toalveolar epithelial cells of the second type. During coronavirusinfection, ACE2 interacts with the receptor-binding domainof the virus spike protein, which leads to endocytosis of viralparticles and their internalization . Theseevents result in severe acute respiratory syndrome, lung tissuedamage, and extensive inflammation .It is important to note that the first stages of coronavirusinfections caused by SARS-CoV, MERS-CoV and SARSCoV2have significant similarities.As noted above, the source of human coronavirus diseases wasanimals. In 2003, Chinese researchers found that bats werecarriers of the SARS-CoV coronavirus in humans through anintermediary \u2013 Himalayan civets, whose meat is considereda delicacy in Chinese cuisine . The basis for this conclusion was 99.8 % similarityof the SARS-CoV genome with the virus isolated from batsand Himalayan civets. Bats are also natural carriers of theMERS-CoV coronavirus, and the camel is an intermediatecarrier of the virus to humans .It is worth noting that there are several animal species susceptibleto SARS-CoV infection: ferrets, Syrian hamsters, cats,and several primates: macaques, African green monkeys, andmarmosets . It is assumed that otheranimals may be susceptible to the novel coronavirus SARSCoV-2 . However, these infected animalsshow minimal signs of impairment and generally lack the clinicalsymptoms associated with human coronavirus infectionIn connection with the above, the strategy for creatingmodel animals is based on the technology of introducing thehuman ACE2 gene, the main receptor for coronaviruses, intotheir genome. Indeed, in one of the first works on the creationof transgenic mice susceptible to coronavirus infection, apK18-hACE2 recombinant DNA construct was developed,including the 5\u2032-promoter and the 1st intron (with a mutationin the 3\u2032-splice of the acceptor) of the human CK18 gene(encodes cytokeratin-18), as well as the translational enhanceralfa of the alfalfa mosaic virus , human ACE2cDNA and a 3\u2032 sequence including exon 6, intron 6, exon 7 andpolyA signal element of the human CK18 gene . According to the authors\u2019 intention, all elements werepresent in the construct to ensure a high level of its expressionin epithelial cells. A purified DNA fragment of 6.8 kb excisedfrom pK18-hACE2 was injected into the pronuclei of hybrid(C57BL/6Jx SJL/J) zygotes to obtain transgenic animals.In the experiment described above ,three lines of transgenic mice were obtained from different founders. It should be noted that the chosen technology providesrandom insertion of the transgene into the recipientgenome, with a different number of copies. According to theauthors, the number of transgene copies in the lines variedfrom 4 to 10. The transgene expression was observed in varioustissues of the obtained mice: lungs, small intestine, liverand kidney, and at a low level was noted in the brain.After intranasal SARS-CoV infection of transgenic CK18-hACE2, animals of all three lines died after the 7th day aftervirus inoculation. Moreover, mice carrying more transgenecopies died already on the 4th day after infection. It is importantto note that weight loss was observed in all transgenicmouse strains. The high titer of the virus was determined inthe lungs compared with the control and reached the highestlevel on the 2nd day after infection. These data suggest increasedviral replication as a key factor in the developmentof severe disease in transgenic animals. Interestingly, despitethe expression of human ACE2 in the small intestine, liver,and kidney, the presence of the virus was not found in them.Among three tested lines of transgenic mice, only in one viruswas detected in the brain at a low level, although the level oftransgene expression was at the background level.Histological analysis of the lungs on the 2nd day of infectionshowed signs of vascularization and peribronchiolarinflammation, and then there was an expansion of the zoneof the inflammatory process, cell infiltration and desquamationof the cell epithelium in two lines of transgenic mice.In general, the pattern of intranasal infection of transgenicCK18-hACE2 lines showed similarities with the developmentof acute respiratory syndrome in humans caused by SARSCoVinfection, in other words, these animals can be used asmodel objects for studying the pathogenesis of coronavirusinfection . Morerecently, CK18-hACE2 infection of mice with SARS-CoV-2has shown similarities with clinical manifestations of humanCOVID-19 .Almost simultaneously, another group of researcherscreated transgenic mice expressing human ACE2 under thecontrol of the constitutive CAG promoter .The cDNA sequence of the human ACE2 gene was insertedinto the expression vector pCAGGS/MCS, which containedin the 5\u2032-sequence of the enhancer of the early promoter of thecytomegalovirus fused with the promoter of the chicken actingene, and in the 3\u2032-region splicing sites of the rabbit globingene. The total size of the pCAGGS-ACE2 expression vectorwas 7750 bp. A DNA fragment of this cassette was injectedinto the pronuclei of C57BL/6J \u00d7 C3H/HeJ hybrid zygotes.Among the F0 offspring born from experimental zygotes, fivetransgenic animals were identified, of which two founders,AC70 and AC63, gave rise to two lines. RT-PCR analysisshowed the presence of human ACE2 transgene transcriptsin the stomach, heart, muscles, brain, kidneys, lungs, andsmall intestine.Infection of transgenic mice with SARS-CoV showed thefollowing symptoms: permanent weight loss, shortness ofbreath, and uncontrolled motor activity. The death of animalswas observed after the 3rd day of infection and ended in totallethality by the 8th day. The reproduction of the virus occurred mainly in the lung tissue, while in other samples: swabs fromthe oral cavity, blood, heart, spleen, kidney, urine or feces, thevirus was not detected. Summing up, the authors concluded that the resulting transgenic mouse linesare susceptible to SARS-CoV infection and exhibit externalsigns similar to those of humans, including the lethal outcomeof infected animals. According to the authors, such micemay be useful for studying the pathogenesis of SARS-CoVinfection.In 2007, a third article on the creation of transgenic micesusceptible to SARS-CoV infection appeared . This group of researchers used a construct that includedthe mouse Ace2 gene promoter fused to the human ACE2 gene.The DNA of this construct was injected into the zygotes ofICR mice and the birth of transgenic animals was observed.Human ACE2 expression was detected in the lungs, heart,kidneys, and small intestine. On the 3rd and 7th days after infectionwith SARS-CoV, virus replication was observed in thelungs as well as signs of lung damage: interstitial hyperemiaand hemorrhages, monocytic and lymphocytic infiltration, aproliferation of the alveolar epithelium and its desquamation.Interestingly, much later , after intranasalSARS-CoV-2 infection of these transgenic mice, a moderateweight loss was observed in the first five days, but no deathswere recorded in any case. The target and site of replicationof COVID-19 was lung tissue, which resulted in the developmentof signs of pneumonia. Thus, the transgenic mouse linecreated in 2007 has become a convenientplatform for studying the pathogenesis of the two coronavirusesSARS-CoV and SARS-CoV-2.Using the classical technology of transgenesis \u2013 microinjectionof DNA expression vectors into the pronuclei of zygotes,which are randomly inserted into the recipient genome and, which results in the expression ofthe transgene varying in different founders. One such studyworthy of attention is the generation of transgenic C3B6mice carrying human ACE2 under the control of an HFH4promoter specific for ciliated lung epithelial cells . Human ACE2 expressionwas found in the lungs, brain, liver, and kidneys of transgenicHFH4-hACE2 mice. Intranasal infection with SARS-CoV orone of its WIV1-CoV strains caused weight loss in the firstdays of infection and death of animals after the 6th day fromthe moment of infection . It is importantthat vaccines were tested on these mice and their positiveeffect was observed against both types of coronavirus. Later,these transgenic mice were successfully used to test antiviraltherapy against COVID-19 .It makes sense to dwell on the study of the Russian groupof A.V. Deikin, which for the first time provides protectivemeasures to the researchers themselves against being infectedwith coronaviruses from transgenic mice .The authors created a cassette consisting of two main elements:the pKB1 vector and the hACE2 open reading frame.pKB1 ampicillin-resistant vector was designed for cloning ofgenes, the expression of which depends on Cre-recombination, and contains insulators and terminators(\u201cprotecting\u201d the transgene from the influence of nearbysequences), CAG promoter and STOP cassette. In addition,the vector contains the IRES element of the encephalomyocarditisvirus, the GFP reporter gene, and the polyA signalof the SV40 virus. It is important that the expression of thehuman ACE2 transgene is activated only after removal of theSTOP cassette by Cre-recombinase.The recombinant DNA cassette was microinjected intoF1 hybrid mouse zygotes (CBA \u00d7 C57BL/6). The resultingtransgenic animals did not express either human ACE2 or thereporter gene. To activate the transgene, transgenic mice werecrossed with B6 mice Cg-Ndor1Tg(UBC-cre/ERT2)1Ejb/1 J(abbreviated as Ubi-Cre) carrying the Cre recombinase geneunder the control of the UBC promoter. In heterozygousACE2-GFP and Cre-transgene mice, the transgene was activatedwith tamoxifen, which activates Cre-UBC, which, inturn, cuts out the STOP cassette and activates the expressionof ACE2 and the reporter gene . Thus,heterozygous mice become susceptible to coronavirus infection.Indeed, direct experiments demonstrated that the virusintranasally inoculated to transgenic mice SARS-CoV2 inducedthickening of alveolar duct septa mediated by diffusehyperplasia of alveolar type II epithelium. Also, the lung tissueunderwent lymphocyte infiltration. It should be emphasizedthat erythrocyte aggregates were present in the lung tissue inabundance, which was indicative of clotting. In contrast tolung tissue samples, no aberrations were found in the histologicalexamination of the brain except for abundant erythrocyteaggregates as a sign of clotting . Allexperimental transgenic mice died on day 5 to 10 after theintranasal inoculation.The COVID-19 pandemic has stimulated the search for newtechnologies for creating model animals \u2013 laboratory mice.The development of targeted modification of human and animalgenomes using CRISPR/Cas9 technology has opened upthe prospect of obtaining \u201chumanized\u201d animals, in the genomeof which target endogenous genes can be replaced by homologoushuman genes. An example is the insertion of the humanACE2 cDNA into the coding sequence of the endogenousAce2 gene in C57BL/6 mice using CRISPR/Cas9 technology. The cDNA of the human ACE2 gene wasinserted into exon 2 of the mouse Ace2 gene in mouse zygotes.Such an insert inactivated the endogenous Ace2 gene, and tovisualize human ACE2 expression, the fluorescent proteinreporter gene tdTomato (red glow) was inserted at its 3\u2032-end,together with the IRES site and the polyA sequence. Amongmice born from experimental zygotes, transgenic animals witha target insertion of the human ACE2 gene were identified.Such mice were susceptible to intranasal SARS-CoV-2 infectionat a young and adult age; the virus affected the lungs,trachea and brain. With intranasal infection, interstitial pneumoniadeveloped, similar in manifestations to that of a personinfected with SARS-CoV2, but without a lethal effect. It isclear that such genetically modified mice are seen as an attractivemodel of human coronavirus infection and could potentially serve as a platform for vaccine trials and pharmacologicaldrug testing.An essentially similar approach to \u201chumanization\u201d of themouse Ace2 gene by insertion of the human ACE2 cDNA, hasbeen implemented in C57BL/6 and BALB/c mouse embryonicstem cell (ESC) lines using CRISPR/Cas9 technology. It is appropriate to recall that the used ESClines are capable, after injection into the cavity of tetraploidblastocysts, to replace endogenous cells of the internal mass,as a result of which transgenic descendants developed fromdonor ESCs are born. Transgenic mice thus generated, namedC57BL/6NAce2em2/CCLA andBALB/c-Ace2em1/CCLA, weresusceptible to intranasal SARS-CoV2 infection, althoughthey differed from those obtained by S.-H. Sun et al. (2020)by a number of traits from transgenic mice. Thus, to date, anumber of lines of \u201chumanized\u201d mice that carry the humanACE2 transgene and are susceptible to coronavirus infectionand potentially capable of modeling human coronavirus pathologyhave been created.To sum up, it should be noted that despite the variety of createdtransgenic mouse lines susceptible to coronavirus infection(see the Table), the most popular among researchers are CK18-hACE2 mice created by the group P.B. McCray et al. (2007).According to PubMed, from 2020 to 2022, 101 articles thatused this line as a model animal for the study of pathogenesisand coronavirus infection were published. Nevertheless,the development of new models continues, since the sourceof supply of mice of the CK18-hACE2 line is the JacksonLaboratory (USA), which supplies them only for experiments,without the right to breed them in national animal facilitiesin other countries.The authors declare no conflict of interest.Bader M. ACE2, angiotensin-(1-7), and Mas: the other side of thecoin. Pf lugers Arch. 2013;465(1):79-85. 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Leveraging a large multicenter cross\u2010sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE\u2010HS) correlate with clinical features.d\u2009\u2265\u2009.5) were used to train an event\u2010based model (EBM), which estimates a sequence of disease\u2010specific biomarker changes from cross\u2010sectional data and assigns a biomarker\u2010based fine\u2010grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance.We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1\u2010weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA\u2010Epilepsy consortium, comprising 804 people with MTLE\u2010HS and 1625 healthy controls from 25 centers. Features with a moderate case\u2013control effect size , age at onset , and ASM resistance . However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE\u2010HS with mild or nondetectable abnormality on T1W MRI.In MTLE\u2010HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman From cross\u2010sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE\u2010HS subjects in other cohorts and help establish connections between imaging\u2010based progression staging and clinical features. We estimated the sequence of progression of subcortical and neocortical atrophy in MTLE with HSAbnormality started in the hippocampus, followed by decreased cortical thickness in the parietal and frontal lobes, thalamic volume, and ventricular expansionImage\u2010based disease stages were correlated with duration of illness, age at onset, and drug resistanceAssociations were driven by MTLE\u2010HS cases showing mild volume loss in the ipsilateral hippocampus that was indistinguishable from variation in the control group1Epilepsy is characterized by recurrent seizures caused by excessive and abnormal neuronal activity in the cortex. Moreover, there is consistent evidence indicating decreased gray matter volume in people with epilepsy (PWE) compared to healthy controls. Quantitative analysis of MRI data from PWE in a large multicenter cohort showed reduced cortical thickness and subcortical volume in specific brain regions according to epilepsy type.Whether seizures, antiseizure medication (ASM), head injuries, the epileptogenic process, the maintenance of seizure occurrence, or other comorbidities cause the observed loss of brain tissue is a much\u2010discussed question. Many studies have found that gray matter thickness is correlated with the duration of illness in the common epilepsies, indicating that these cross\u2010sectional differences may be progressive.In this work, we investigated disease progression in patients with radiographically identified sclerosis of the hippocampus or the mesial temporal lobe (MTLE\u2010HS) using the event\u2010based model (EBM). In brief, the EBM is a machine learning approach that learns the most likely ordering of biomarker changes from cross\u2010sectional data. The EBM was originally developed to study progressive loss of brain tissue in Alzheimer and Huntington diseases.22.1We analyzed data from the ENIGMA\u2010Epilepsy working group2.2Because ENIGMA\u2010Epilepsy is a multicentric study, the data are subject to center\u2010specific biases arising from various factors. Thus, all 156 regional brain measures were harmonized for center biases using NeuroCombat,2.3Studies have shown unilateral and bilateral alterations of structural connectivity and structural measures in left and right MTLE\u2010HS patients, with the ipsilateral regions being more strongly affected.2.4Previous studies2.5dd uses the median and mean absolute deviation in place of the mean and SD, respectively, and is more resilient against outliers.d|\u2009\u2265\u2009.5) was required for inclusion into disease progression modeling. We also evaluated a more lenient threshold (robust Cohen |d|\u00a0\u2265\u00a0.4).First, we sought to identify brain regions with sufficient epilepsy\u2010related atrophy to be used for progression modeling. We used a robust variant of Cohen 2.6The selected regions were used as inputs to the EBM.2.7U test to test for a difference in EBM\u2010assigned stage regarding drug\u2010resistant status.We hypothesized that subjects with advanced EBM stages were more likely to have a longer duration of illness, to have earlier disease onset, and to be drug\u2010resistant. To determine whether individuals' EBM stage is related to illness duration or age at onset, we computed Spearman rank correlations between EBM stage and the duration of illness (in years) at the time of imaging and age at onset, respectively. Furthermore, we used the Mann\u2013Whitney 3Table\u00a03.1d|\u2009\u2265\u2009.5) were ipsilateral hippocampal volume and its BASI, ipsilateral thalamic volume, cortical thickness of bilateral superior parietal gyrus, and ipsilateral precuneus and ipsilateral lateral ventricle volume (Table\u00a0d) ipsilateral to the seizure focus were stronger than those in the corresponding contralateral region for the surface area but not for cortical thickness nor for subcortical volumes . Effect sizes for cortical thickness were stronger than effect sizes for surface area . Use of the lower Cohen d cutoff of .4 produced 12 additional features for EBM modeling , which was not observed in cases assigned to Stage 0 (d\u00a0=\u00a0\u2212.17) or Stages 1\u20132 (d\u00a0=\u00a0.16).Ipsilateral hippocampal volumes in cases at Stage 0 were significantly larger than in cases assigned to later stages . After excluding cases at Stage 0, the correlation remained marginally significant . Thus, the correlation is driven by the significant difference in duration of illness between EBM Stage 0 (mean\u00a0=\u00a015.7\u2009years) and non\u20100 . The same pattern was observed for age at onset; EBM stage and age at onset were negatively correlated , but the effect vanished in the subset of cases at Stages 1\u20137 . Age at onset was significantly later for Stage 0 cases compared to non\u20100 cases . EBM stages differed between MTLE\u2010HS cases that were resistant (n\u00a0=\u00a0363) or responsive (n\u00a0=\u00a045) to ASMs in the 12\u2009months prior to MRI .MTLE\u2010HS patients assigned to early EBM stages showed a relatively shorter illness duration than those in later stages Figure\u00a0. Duratio4We applied data\u2010driven disease progression modeling to a large, multicenter imaging study of epilepsy to characterize the progression of MTLE\u2010HS. We identified a characteristic order of MRI morphometric changes originating in the ipsilateral hippocampus. We did not identify statistically significant correlations between the accumulation of imaging changes (EBM Stages 1\u20137) and available clinical markers of disease duration or severity in this cohort.d|\u2009\u2265\u2009.5; |d|\u2009\u2265 .4 for a sensitivity analysis; Table\u00a0For the progression modeling, we retained features exhibiting a medium effect size between cases and controls (|d\u00a0=\u00a0\u22121.76), there is significant variability in volume loss at the individual level. Approximately half the subjects with HS exhibit hippocampal volume that is within the normal rangeAt first glance, it appears surprising that many MTLE\u2010HS cases were assigned to Stage 0 despite the loss of hippocampal volume being one of the hallmark signs of MTLE\u2010HS. Two factors contribute to this discrepancy. First, the radiologic diagnosis of HS is based on multiple imaging sequences, whereas hippocampal atrophy, as defined on T1W images, is only one component of HS.Duration of illness is typically used as a proxy for progression in cross\u2010sectional studies.d\u00a0=\u00a0\u2212.14) missed the inclusion threshold for the EBM. Thus, the analysis could not provide further insights on whether untreated unilateral HS will lead to bilateral HS. However, PWE assigned to later EBM stages did present with reduced volume in the contralateral hippocampus, whereas this was not the case for PWE assigned to earlier stages, illustrating the potential of EBM.Longitudinal studies of PWE reveal cortical atrophy beyond the expected range of normal aging.The staging of individual MTLE\u2010HS patients using the trained EBM allowed us to investigate associations with duration of illness and clinical markers such as ASM resistance. In agreement with Whelan et al.There were several limitations in our study. First, this ENIGMA\u2010Epilepsy cohort is not a population\u2010based cohort but represents data mostly from tertiary epilepsy centers, and therefore the findings may not be generalizable to the overall epilepsy population. Also, within the ENIGMA\u2010Epilepsy cohort, we observed sampling bias regarding availability of ASM response data Table\u00a0; PWE witIn conclusion, we estimated a sequence of progressive pathology in MTLE\u2010HS that can be used to assign patients to fine\u2010grained, image\u2010based disease stages. Beyond Stage 0, the EBM staging did not correlate with duration of illness, age at onset, or drug\u2010resistance. However, our EBM model trained on the ENIGMA\u2010Epilepsy data can be used to stage MTLE\u2010HS subjects in other cohorts with relevant clinical data and help establish connections between imaging\u2010based progression staging and other clinical features such as the lifetime number of seizures and detailed information on ASM exposure.Cohort principal investigators: A.A., A.B., A.G., A.L., B.W., C.R.M., D.J.S., F.C., G.D.J., G.P.W., H.S.\u2010Z., K.H., L.Co., M.R., N.Ba., N.Be., N.D., N.K.F., P.S., R.G., R.W., S.M., S.M.S., S.S.K., T.J.O., T.R. Contributed to the editing of the manuscript: A.A., A.B., A.G., A.R., A.E.V., B.Ben., B.Ber., C.R.M., C.M., D.C.A., D.J.S., E.D.\u2010B., E.G., E.K., E.L., F.C., G.D.J., G.P.W., J.S.D., K.H., L.Ca., L.Co., L.M.A., L.V., M.A., M.G., M.M., N.Be., N.J., N.P.O., P.M.D., P.S., S.E.M., S.I.T., S.L., S.M.L., S.M.S., S.S.K., T.J.O., V.I.D., L.B., S.B.V., E.B. Imaging data collection: A.B., A.R., B.Ben., B.W., C.d.B., C.D.W., C.L.Y., E.C.\u2010B., E.D.B., E.K., E.L., F.C., F.F., G.P.W., J.R., K.H., L.Co., L.V., M.A., M.E.M.\u2010S., M.M., M.R., N.Be., O.D., P.M., P.M.D., P.S., R.G., R.H.T., S.A., S.S.K., Y.W., L.B., E.B. Imaging data analysis: A.C., B.A.K.K., B.C., B.S., C.d.B., C.D.W., C.L.Y., D.C.A., E.D.\u2010B., J.R., K.H., L.M.A., L.V., M.E.C., M.D., M.L., M.R., M.T., N.J., P.K., P.M., P.N.T., R.G., R.K., S.F., S.M.L., S.S.K., T.W.O., Y.W., S.B.V. Core analysis group: A.A., C.R.M., D.C.A., N.P.O., S.M.L., S.M.S. Core writing group: A.A., C.R.M., D.C.A., N.P.O., S.M.L., S.M.S. Patient recruitment, phenotyping: R.H.T. ENIGMA\u2010Central: P.M.T., S.I.T., N.J.B.Ben. is cofounder of AIRAmed, a company that offers brain segmentation. C.D.W. is an employee of Biogen. D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun. K.H. has received honoraria and speaker fees from UCB, Eisai, and GW Pharma L.V. reports research funding from Biogen Australia, Life Molecular Imaging, and Eisai. N.K.F. has received honoraria from Arvelle, Bial, Eisai, Philips/EGI, and UCB. N.J. is MPI of a research grant from Biogen for work unrelated to the contents of this article. P.S. has received speaker fees and served on advisory boards for Biomarin, Zogenyx, GW and Pharmaceuticals; has received research funding from ENECTA, GW Pharmaceuticals, Kolfarma, and Eisai. P.M.T. has received a research grant from Biogen and was a paid consultant for Kairos Venture Capital for projects unrelated to this work. None of the other authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.APPENDIX S1Click here for additional data file."} +{"text": "Eremias kokshaaliensis Eremchenko et Panfilov, 1999, together with other central Asian racerunner species, is included in the Eremias multiocellata complex. In the present work, for the first time, the results of the analysis of historical mitochondrial DNA (barcode) are presented and the taxonomic status and preliminary phylogenetic relationships within the complex are specified. We present, for the first time, the results of the molecular analysis using historical DNA recovered from specimens of several species of this complex using DNA barcoding.The Kokshaal racerunner, Eremias. Currently, the genus Eremias includes 40 species [Eremias multiocellata\u2014E. przewalskii complex belong to the taxonomically most complicated group of the genus Eremias [E. stummeri Wettstein, 1940 st. nov. Eremchenko et Panfilov, 1999; Szczerbak\u2019s racerunner E. szczerbaki Eremchenko et Panfilov, 1999 status nov.; Yarkand racerunner E. yarkandensis Blanford, 1875; Kokshaal racerunner E. kokshaaliensis Eremchenko et Panfilov, 1999; Kashgar racerunner E. buechneri Bedriaga, 1907; Dzhungar racerunner E. dzhungarica Orlova et al., 2017; multi-ocellated racerunner E. multiocellata G\u00fcnther, 1872; Przewalski\u2019s racerunner E. przewalskii ; E. m. var. reticulata Bedriaga, 1912 (status questionable). The genetic variability and phylogenetic relationships between E. multiocellata, E. przewalskii and allied taxa remain insufficiently studied. Further progress in this area is hampered by complicated taxonomy and a lack of verified identifications and comparisons with type material. Until recently, the multi-ocellated racerunner, Eremias multiocellata, was considered as a single species with several subspecies, only one of which, E. m. yarkandensis, was recognized before 1992 in the territory of the former USSR [E. buechneri [E. multiocellata complex are represented by several distinct subspecies [Modern phylogenetic methods allow a look into the past with the extraction of DNA from specimens collected a century and a half ago. Collections at the Zoological Institute in St. Petersburg and Moscow State University have herpetological samples stored in ethanol that have never been exposed to formalin that go back to the 1880s. This study accesses this unique resource to answer taxonomic questions in the lizard genus species ,3,4. The Eremias ,6,7,8, wuechneri . This pouechneri . As a reE. stummeri Wettstein, 1940 inhabiting the Chu-Issyk-Kul Lake basin, E. szczerbaki Eremchenko et Panfilov, 1992 from the inner Tien Shan and the Naryn River basin, and E. yarkandensis Blanford, 1875 from the Tarim basin in China were recognized as distinct species [E. kokshaaliensis Eremchenko et Panfilov, 1999 is distributed in the extreme northeast of Kyrgyzstan (Sary-Jaz and Pokrovsky Syrts) and can be easily distinguished from all previous forms by a slender habitus, a miniature head and a speckled pattern of the dorsal side of the body. The validity of these taxa was confirmed by the authors from the results of laboratory hybridization and some craniological characteristics: the presence and size of pterygoid teeth, the texture of septomaxillae and the shape of the premaxillary process [Eremias sp. from the southern slopes of the central Tien Shan were analyzed and discussed.Later on, species . The Yar process . All spe process . UnfortuPhrynocephalus rossicowi (Reptilia), Dipus saggita , Blarinella griselda , Tonkinodentus lestes (Chilopoda), etc. [Museum collections, especially type specimens, represent a very important source for taxonomic studies, even in the field of molecular phylogenetics. DNA degrade in historical specimens, but modern methods and special facilities allow us to obtain data from such difficult material, including successful attempts to extract DNA from formalin-fixed museum specimens ,16,17,18a), etc. ,24,25,26E. multiocellata complex based on the molecular identification of museum collections: type specimens of E. kokshaaliensis and historical specimens of E. buechneri, as well as other collections of these Eremias species from China and Kyrgyzstan, including those previously used in molecular analysis [The aim of the present paper is to analyze the taxonomic status and distribution of species of the analysis . We alsoThe materials for this study were the following museum specimens in the herpetological collections of Zoological museum of Lomonosov Moscow State University, Moscow, Russia (ZMMU), Zoological Institute of Russian Academy of Science, St. Petersburg, Russia (ZISP) and Institute of Biology and Pedologyof the National Academy of Sciences, Bishkek, Kyrgyzstan (BSI):E. kokshaaliensis: 4 topotypes: ZMMUR-3302 : Kyrgyzstan, central Tien Shan, Sary-Dhaz River at the confluence with the Inylchek River, 05.08.1967, leg. S.L. Pereshkolnik.E. kokshaaliensis: 15 paratypes: BSI R-000587\u2013000591, 000596, 000599, 000601 : Kyrgyzstan, central Tien Shan, Sary-Dhaz, vicinity of Engylchek (Enylchek), 08.1986, leg. V.K. Eremchenko.E. kokshaaliensis: 5 paratypes, ZISP R-8277, males: China, Xinjiang, Kara-Teke, 1889. leg. M.V. Pevzov.E. kokshaaliensis: paratype ZISP R-8289, female: China, Xinjiang, Taushkan \u2013Darya, 1891, leg. M.V. Pevzov.E. kokshaaliensis: paratype ZISP 8292, female: China, Xinjiang, southern Tien Shan, 1891, leg. M.V. PevzovE. kokshaaliensis: ZMMU R-14327, female: China, Xinjiang Uygur autonomous region, Aksu district, 35 km northeast of Aksu city, 1110 m a.s.l., spurs of Talyktau mountain ridge, 23.08.2014, leg. E.A. Dunayev.E. kokshaaliensis: ZMMU R-14328 : China, Xinjiang Uygur autonomous region, Aksu district, 89 km northeast of Aksu city, 1364 m a.s.l., east spurs of Pobeda Peak Mountain, 24.08.2014, leg. E.A. Dunayev.E. kokshaaliensis: ZMMU R-14329 , 60 km northeast of Aksu city, 1435 m a.s.l., east spurs of Pobeda Peak Mountain, 24.08.2014, leg. E.A. Dunayev.E. kokshaaliensis: ZMMU R-14330 m a.s.l., 25\u201326.08.2014, leg. E.A. Dunayev.E. buechneri: ZISP R-9131, 2 females: China, near Tolan-Khodjha River in Kashgaria, 1890, leg. V.I. Roborovsky.In the molecular genetic analysis, seven specimens of lizards of this complex (OK624437-OK624443) were used .MtDNA sequencing and analyses. Tissue samples of Eremias sp. were taken from seven specimens preserved in ethanol including five specimens of type series from collections of ZISP and BSI.Eremias multiocellata-complex sequences from GenBank was carried out in the ZMMU Laboratory of Historical DNA, equipped exclusively for the work with museum DNA specimens, where no previous work on fresh tissues had been performed. DNA was extracted and purified using the Qiagen QIAamp DNA MiniKit with some changes: overnight lysis step at 56 \u00b0C and two steps of elution with AE buffer, each with 50 \u03bcL of buffer and 5 min of incubation at room temperature. We amplified a fragment of the COI (cytochrome oxidase I subunit) gene of mitochondrial DNA. DNA was highly degraded, so only short fragments (100\u2013200 bp) were obtained using a combination of internal primers designed for this study. Five primer pairs for five overlapping fragments were manually developed using Bioedit ,29 and a GenBank .Amplification was performed in 22 \u03bcL reaction volumes containing 2 \u03bcL DNA, 4 \u03bcL of Evrogen HS-Screen mix, and 1 \u03bcL of each primer (10 pmol/\u03bcL). All stages of the extraction process included a blank as a negative control run in parallel. PCR products were visualized using a 1% agarose gel. PCR products were sequenced at the Evrogen laboratory using an ABI PRISM 3500xl sequencer with BigDye Terminator Chemistry v. 3.1 using PCR primers.Eremias ssp. were deposited in GenBank under the following accession numbers: OK624437\u2014OK624443. Other sequences of Eremias were downloaded from GenBank [E. multiocellata (KY366658 and KY366636) and Darevskia rudis (MN613693) were included as outgroups. The final alignment used for the phylogenetic analyses comprised 676 bp for 52 ingroup sequences of Eremias spp. Mean inter- and intraspecific uncorrected genetic p-distances and sequence characteristics were calculated using MEGA 6.1.Short fragments were first aligned using Seqman v5.06 software , assembl GenBank ,27 (TablPhylogenetic trees were reconstructed by Bayesian inference criteria (BI), by maximum-likelihood (ML) and maximum-parsimony (MP) methods. The optimal partitioning schemes for Bayesian inference analysis were identified using PartitionFinder software using grEremias. Of the 676 aligned sites, 540 were found to be conserved, 130 variable and 110 parsimony-informative; the transition\u2013transversion bias was estimated at 4.11 . The nucleotide frequencies on the light strand were 24.5% (A), 28.5% (T/U), 29.2% (C), and 17.8% (G). Uncorrected p-distances are provided in p-distances demonstrates two gaps: at 3.0 and 6\u20137%, respectively from Kashgaria, China. The resulting phylogeny and fall into four main groups: E. szczerbaki (PP/BS/MP = 1/99/100), E. stummeri (PP/BS/MP = 1/99/100), E. buechneri, and part of E. kokshaaliensis group A (PP/BS/MP = 1/99/93). The rest of the sequences form another group with low support (PP/BS/MP = 0.7/-/53), which consists of E. yarkandensis, E. dzhungarica, E. cf. buechneri and the rest of E. kokshaaliensis (Group B).The extensive type series (35 specimens) of cription , includehylogeny mainly aEremias kokschaaliensis are divided into two groups. One group of E. kokschaaliensis A form a clade with Eremias specimens from Aksu (China) with high support (PP/BS/MP = 1/0.99/93); E. kokshaaliensis specimen no. R-8289 ZISP has a basal position within this group (PP/BS/MP = 0.98/0.88/52). The uncorrected within-group p-distance within this clade is 1.41%.Our results showed that the studied samples of E. kokshaaliensis, which are paratypes of E. kokschaaliensis , form the second group: E. kokschaaliensis B (PP/BS/MP = 0.89/87/-). The resolution of their position is too low, and it would be impossible to assign them to any form until more molecular data have been obtained and studied.Three specimens of the type series E. kokshaaliensis from the type series of group A is easily recognizable by the characteristic of the mottled pattern of the dorsal surface of the body of ethanol-preserved specimens , it occupies sandy terraces near the river and rough-stony lower slopes of the mountains. Here they are quite common, and in one hour of the tour, there can be from 18 to 30 individuals [E. kokshaaliensis group B from Kara-Teke.The ividuals . There iE. buechneri no. R-9131 ZISP .The historical specimen of 131 ZISP represenE. kokshaaliensis and E. buechneri without newly collected specimens from Kashgaria and the results of DNA analysis.It is currently not possible to discuss the phylogenetic relationships of E. kokschaaliensis Eremchenko et Panfilov, 1999 and E. buechneri Bedriaga, 1907, which were previously described only on the basis of external morphology and partially on osteological and other characteristics. An important result is the revealing of the heterogeneity of the E. kokshaaliensis type series. The two phylogenetic groupings are geographically separated by about 300 km . This novel DNA sequencing of historical specimens (ZISP) of"} +{"text": "Argyris Stringaris was initially included as an author in the original publication [lication . HoweverAuthor Contributions: Conceptualization, C.N.; methodology, C.N.; software, C.N.; validation, C.N.; formal analysis, C.N., I.R., I.G., A.S. and E.L.; data curation, C.N., D.P., K.M., I.G., K.K., A.S., E.T., A.G., K.L., I.K., N.S. and G.O.; writing\u2014original draft preparation, C.N., D.P., I.R., A.S., E.L. and M.C.-T.; writing\u2014review and editing, C.N., I.R., I.G. and M.C.-T.; visualization, C.N.; supervision, E.L.; project administration, E.L. All authors have read and agreed to the published version of the manuscript.Acknowledgments: The authors would like to thank all the respondents to this study who took the time to complete the questionnaire. We would like to thank Argyris Stringaris for his contributions to coordinating sample collection and discussions regarding the clinical aspects of the paper. We would also like to thank the Hellenic COVID-19 imPact survEy (HOPE) Consortium for their contribution during the data collection process: Lagakou E., First Psychiatric Department, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece; elagakou@gmail.com. Mamaki, E., Mental Health Center, General Hospital \u201cG. Hatzikosta\u201d, Ioannina, Greece; g.vottis@yahoo.gr. Neou, E., Hellenic Centre for Mental Health and Research, Athens, Greece; evaneou@gmail.com. Polaki, O., Community Mental Health Center for Children and Adolescents in N.Smyrni, Division of Psychiatry, \u201cAsklepieion Voulas\u2019 General Hospital, Attica, Greece; olympiapolaki@yahoo.gr. Priftis D., University Mental Health Research Institute; icedale@gmail.com. Triantafyllou, G., Second Psychiatric Department, \u201cAttikon\u201d University Hospital, National and Kapodistrian University of Athens, Athens, Greece; g_triantafillou@yahoo.gr. Valvi E., Athens Child and Adolescent Mental Health Centre, General Children\u2019s Hospital \u201cPan. & Aglaia Kyriakou\u201d, Athens, Greece. Vassara, V., Community Mental Health Center for Children and Adolescents, Department of Psychiatry, University Hospital of Ioannina, Ioannina, Greece; vasilikivassara@gmail.com.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "Mycobacterium tuberculosis infection or from reactivation of pre-existing latent TB infection (LTBI). Although individuals with LTBI do not have clinical TB symptoms, they are a reservoir for active TB cases and pose a significant challenge to the global effort to eliminate TB. Strategies to reduce the burden of TB vary among countries, and are, in part, determined by the local prevalence of LTBI and active TB [Active tuberculosis (TB) can develop from newly acquired ctive TB . Developctive TB . To addrAll study participants were Malawian adults aged at least 18 years who had received Bacillus Calmette-Gu\u00e9rin vaccination during childhood but had no history of previous TB treatment or clinical and laboratory evidence of active TB. They were tested for LTBI using the QuantiFERON-TB Gold Plus (QFT-Plus) interferon gamma release assay (IGRA) according to the manufacturer's instructions. Informed written consent was obtained from all participants and the study protocol was approved by the College of Medicine Research Ethics Committee in Malawi (protocol P.02/18/2356) and the Liverpool School of Tropical Medicine Research Ethics Committee in the UK (protocol 17-032).P\u200a=\u200a0.02]. However, the prevalence of LTBI was similar across different age groups of whom were PWH. Of the 66 PWH, 55 (83.3%) were on ART. Ten participants, six of whom were PWH, had indeterminate QFT-Plus results and were excluded from further analysis. Of the remaining 155 individuals, 68 [43.87% [95% confidence interval (CI) 35.92\u201352.06] had positive QFT-Plus results, indicating that they had LTBI. Subgroup analysis by sex revealed that LTBI was more prevalent among males than females [46 of 88 males vs. 22 of 67 females , + T-cell count. We found that HIV infection, male sex and undetectable HIV viral load were independent risk factors for LTBI [odds ratio (OR) 6.81, CI 1.79\u201328.66, P\u200a=\u200a0.006; OR 3.02, CI 1.41\u20136.77, P\u200a=\u200a0.006; OR 4.49, CI 1.23\u201319.36, P\u200a=\u200a0.03, respectively, Fig. + T-cell count were not.Next, we performed multiple logistic regression to determine if LTBI was associated with age, sex, HIV status, plasma HIV viral load or peripheral blood CD4The current study reports a high prevalence of LTBI among adults attending HIV services at an urban hospital in Malawi, a country with high TB and HIV prevalence. Our findings are consistent with previous reports from Nigeria and ZimbThe high prevalence of LTBI in SSA is likely indicative of high community transmission of TB. Currently, most countries in the region treat PWH with isoniazid preventive therapy (IPT) for 6\u201336 months \u20139. AlthoWe acknowledge that the small sample size and the hospital-based recruitment may limit generalizability of our study findings, therefore large community-based studies are required to determine the community prevalence of LTBI in Malawi. Nonetheless, our participants were ambulatory and reflect the composition of the communities served by the hospital.In conclusion, the prevalence of LTBI in the study population was high. Males and PWH were at high risk of LTBI. Treating individuals with LTBI in SSA, including lifelong IPT for PWH should complement current active TB case finding strategies to reduce TB incidence and deaths in the region.H.C.M. conceived and designed the experiments. S.C.M.-N., D.T.M., E.T.C. and A.P.C. performed the experiments and analysed the data. S.C.M.-.N. and H.C.M. wrote the article, with input from D.T.M., E.T.C., A.P.C., D.V.M., C.K., C.M., D.L.T., J.M., L.M., D.G.R., K.C.J. and S.B.S. The authors thank all study participants and staff of the Clinical Investigation Unit, Malawi Liverpool Wellcome Clinical Programme, Kamuzu University of Health Sciences and Queen Elizabeth Central Hospital for their support and co-operation during the study.The current work was supported by an African Research Leader Award MR/P020526/1 awarded to H.C.M. and S.B.S., jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordant agreement and are part of the EDCTP2 programme supported by the European Union. The work was also supported by the National Institutes of Health (USA) award AI155319 to D.G.R. A core grant 206545/Z/17/Z from Wellcome supports the Malawi Liverpool Wellcome Clinical Research Programme.There are no conflicts of interest."} +{"text": "Phil. Trans. R. Soc. B378, 20210351. (Published online 26 December 2022.) (https://doi.org/10.1098/rstb.2021.0351)In the original version of this article, the title contained an error with the inclusion of the word \u2018Editorial\u2019.This has now been corrected on the publisher's website."} +{"text": "The aim of this study is to evaluate the significance of the R.E.N.A.L nephrometry scoring system in predicting perioperative and oncological outcomes and determining the surgical approach of choice for kidney tumors.Patients and Methods: Our study retrospectively reviewed outcomes from the year 2002 to 2017. Mann-Whitney U test was used to compare continuous variables and chi-square test was used to compare categorical variables. Kaplan-Meier estimates and multivariable cox proportional hazard regression were performed to determine an association between the different R.E.N.A.L categories and disease recurrence or mortality.A total of 325 patients underwent kidney surgery The most common R.E.N.A.L score category in our cohort study was intermediate (41.2%), followed by low, (33.2%) and high (25.5%). Patients with a high R.E.N.A.L score had worse perioperative outcomes compared to those with a low R.E.N.A.L score. High R.E.N.A.L score patients were 3 times more likely to receive blood transfusions compared to those with a low R.E.N.A.L score , and a statistically significant longer hospital length of stay was also observed between the two groups . In addition, the only predictor of disease recurrence or mortality was a high R.E.N.A.L score (Hazard Ratio (HR) 3.65, 95% Confidence Interval (CI) 1.05\u201312.7, p =\u00a00.041).Our study sheds light on the use of R.E.N.A.L nephrometry score in predicting perioperative, postoperative, and oncological outcomes. Such findings may play a role in optimizing surgical approaches and pre-operative patient counseling. Partial nephrectomy (PN) is the most widely utilized surgical approach in the management of stage 1 localized kidney tumors . PN, wheThe decision to perform PN relies heavily on tumor characteristics; however, patients\u2019 comorbidities and overall general health should also be taken into consideration during preoperative assessment. Older age, male gender, medical comorbidities , smoking and obesity have all been shown to be associated with postoperative complications and decreased survivorship after PN .To objectively evaluate tumor complexity, the R.E.N.A.L nephrometry score has been introduced as a standardized tool that relies solely on anatomical variables. These variables include mass radius, percent volume of the mass that is exophytic, proximity to renal sinus, and location . Other nThe aim of this study is to assess the impact of the complexity of renal tumors, stratified by the R.E.N.A.L nephrometry scoring system, on surgical outcomes, postoperative complications, as well as oncological outcomes in patients undergoing PN versus RN at a single institution, coinciding with adoption of robotic assistance.After institutional review board approval, a retrospective chart review was performed for patients with renal cell carcinoma (RCC) who underwent surgical treatment at a tertiary care center. De-identified data was collected for patients treated between 2002 and 2017 to allow a minimum of 3\u00a0years of patient follow-up. Data extracted included clinical parameters such as age, sex, medical comorbidities, tumor pathologic characteristics , surgical characteristics , approach (open vs laparoscopic vs robotic), estimated blood loss, warm ischemia time), pre-operative renal function, and peri-operative complications. R.E.N.A.L nephrometry score was calculated for all patients and categorized into 3 groups: low (\u22646), intermediate (7\u20139), and high (\u226410).Follow- up visits consisted of one post-operative visit at 1\u20132\u00a0weeks and following that, two visits per year for follow up cross sectional imaging. Disease recurrence was defined as any local or distant tumor detection with or without histopathological confirmation.Descriptive statistics were reported as frequencies and percentages or medians and interquartile ranges (IQR). Univariate analysis was performed to explore associations between R.E.N.A.L categories and patient or tumor characteristics. Mann-Whitney U test was used to compare continuous variables and chi-square test was used to compare categorical variables. The yearly proportion of patients undergoing partial nephrectomy within each R.E.N.A.L category was determined, and trends over time were calculated using linear regression. Multivariable logistic regression was used to explore whether R.E.N.A.L score independently predicted surgery type thus influencing clinical decision making, with a priori adjustment for age, clinical T stage, pre-operative creatinine, medical comorbidities . Model fit was assessed using Hosmer-Lemeshow goodness of fit test. Estimates of the probability of disease recurrence or mortality were calculated using Kaplan-Meier estimates. The log rank test was used to compare outcomes of patients with low, intermediate, and high R.E.N.A.L categories. Multivariable Cox proportional hazard regression was performed to test whether R.E.N.A.L categories were associated with disease recurrence or mortality, controlling for age, gender, pathological stage, grade, histology, and type of surgery. Statistical analysis was performed using Stata\u00ae version 16.1, and statistical significance was deemed at p <\u00a00.05.We identified 235 patients who underwent kidney surgery with complete data for analysis. The median age was 59\u00a0years (IQR 48\u201366) and 167 (71%) were males. None of the patients had a postoperative urinary leak. The most common R.E.N.A.L score category was intermediate (41.2%), followed by low, (33.2%) and high (25.5%). 2\u00a0=\u00a00.402) and intermediate category , but not for high category .The R.E.N.A.L score was also associated with choice of surgical procedure, where PN was performed in 75.6% of cases with low score, vs 54.6% of cases with intermediate score (p\u00a0=\u00a00.004), and only 11.7% of those with high score (p\u00a0<\u00a00.001). On multivariate analysis, after adjusting for age, clinical T stage, preoperative creatinine, and comorbidities, increasing R.E.N.A.L score by one category was associated with a stepwise decrease in odds of undergoing PN compared to patients with low R.E.N.A.L score . However, Over a median follow-up of 4.4\u00a0years (IQR 2.3\u20136.9), 48 patients (20.4%) experienced disease recurrence or mortality. The overall 3, 5, and 10-year freedom of disease recurrence or mortality were 92% (CI 87% \u2013 95%), 81% (CI 75% \u2013 86%), and 62% (CI 51% \u2013 72%). When stratified by R.E.N.A.L category, freedom from disease recurrence or mortality did not differ significantly (log-rank p =\u00a00.1176). On multivariable analysis , the onlIn managing renal masses, the choice of procedure (PN or RN) and approach classically depends on qualitative data such as tumor anatomy, patient characteristics, and surgical expertise. Nephrometry scoring systems played a major role in quantifying and stratifying the complexity of renal masses. The R.E.N.A.L nephrometry score utilizes imaging related factors of renal masses to objectively assess tumor complexity aiding in the decision-making process of the elected procedure and type of approach used . In patiIn keeping with available literature, our series shows that most patients with high R.E.N.A.L score tumors underwent RN as most of these tumors are anatomically complex and thus not amenable to PN . Our datIn our series, patients with a higher R.E.N.A.L score tumors were more likely to receive blood transfusions and have an extended length of hospital stay. Similarly, a systematic review and metanalysis of 20 studies showed a clear increase in the incidence of postoperative complications including hemorrhagic ones and urine leaks for patients with higher R.E.N.A.L score tumors . In addiThe impact of an RCC\u2019s tumor complexity on oncologic outcomes is yet to be established. This study has shown that R.E.N.A.L score has a prognostic effect on significant oncologic outcomes. For instance, patients with low R.E.N.A.L score have a significantly improved survival rate when compared to patients with higher nephrometry scores. Similarly, a higher rate of recurrence and upstaging was revealed with high R.E.N.A.L score tumors. Previously, Kopp et al. showed that high complexity tumors (R.E.N.A.L\u00a0\u2265\u00a010) had a negative impact on progression-free survival . WhereasOur study is not without limitations. To start, our sample consisted of a pool of patients before and after the adoption of robotic assisted surgery at our institution. Complications during the early adoption phase might be in fact related to surgeon expertise which could not be accounted for in our analysis. Moreover, we included a cohort of patients over a long period of time during which indications for PN changed dramatically as this technique was being refined and mastered. Moreover, radiologic data in nephrometry scoring was calculated manually by the authors, which is subject to human error. More importantly, the relatively small sample size of this study might not allow consequential and generalizable conclusions. Another limitation is that our cox regression model was likely underpowered to assess disease recurrence and mortality separately due to limited outcome eventsOur study reiterates the role of the R.E.N.A.L nephrometry score in predicting intra and postoperative complications highlighting its importance in pre-operative surgical planning. Additionally, our results shed light on the significance of a higher R.E.N.A.L score in predicting oncologic outcomes including recurrence and mortality. Future prospective studies investigating the correlation between R.E.N.A.L nephrometry score and oncologic outcomes are needed to further validate its prognostic role in RCC."} +{"text": "Candidatus (Ca.) Liberibacter taxa are economically important bacterial plant pathogens that are not culturable; however, genome-enabled insights can help us develop a deeper understanding of their host-microbe interactions and evolution. The draft genome of a recently identified Liberibacter taxa, Ca. Liberibacter capsica, was curated and annotated here with a total draft genome size of 1.1 MB with 1,036 proteins, which is comparable to other Liberibacter species with complete genomes. A total of 459 orthologous clusters were identified among Ca. L. capsica, Ca. L. asiaticus, Ca. L. psyllaurous, Ca. L. americanus, Ca. L. africanus, and L. crescens, and these genes within these clusters consisted of housekeeping and environmental response functions. We estimated the rates of molecular evolution for each of the 443 one-to-one ortholog clusters and found that all Ca. L. capsica orthologous pairs were under purifying selection when the synonymous substitutions per synonymous site (dS) were not saturated. These results suggest that these genes are largely maintaining their conserved functions. We also identified the most divergent single-copy orthologous proteins in Ca. L. capsica by analyzing the ortholog pairs that represented the highest nonsynonymous substitutions per nonsynonymous site (dN) values for each pairwise comparison. From these analyses, we found that 21 proteins which are known to be involved in pathogenesis and host-microbe interactions, including the Tad pilus complex, were consistently divergent between Ca. L. capsica and the majority of other Liberibacter species. These results further our understanding of the evolutionary genetics of Ca. L. capsica and, more broadly, the evolution of Liberibacter.IMPORTANCE\u201cCandidatus\u201d (Ca.) Liberibacter taxa are economically important plant pathogens vectored by insects; however, these host-dependent bacterial taxa are extremely difficult to study because they are unculturable. Recently, we identified a new Ca. Liberibacter lineage (Ca. Liberibacter capsica) from a rare insect metagenomic sample. In this current study, we report that the draft genome of Ca. Liberibacter capsica is similar in genome size and protein content compared to the other Ca. Liberibacter taxa. We provide evidence that many of their shared genes, which encode housekeeping and environmental response functions, are evolving under purifying selection, suggesting that these genes are maintaining similar functions. Our study also identifies 21 proteins that are rapidly evolving amino acid changes in Ca. Liberibacter capsica compared to the majority of other Liberibacter taxa. Many of these proteins represent key genes involved in Liberibacter-host interactions and pathogenesis and are valuable candidate genes for future studies. Liberibacter Liberibacter capsica, Ca. L. psyllaurous, Ca. L. asiaticus, Ca. L. africanus, Ca. L. americanus, Ca. L. europaeus, Ca. L. brunswickensis, Ca. L. ctenarytainae, and L. crescens , and Ca.lanaceae , Apiacealanaceae , and Urtlanaceae and is alanaceae and zebrlanaceae in the e tissues . Neverthfricanus .Ca. Liberibacter species identified using a metagenomic and phylogenetic approach is Ca. Liberibacter capsica in Argentina and Brazil compared to other Liberibacter taxa. Based on these evolutionary analyses, we highlight candidate proteins in Ca. Liberibacter capsica that may be important for host-microbe interactions in the evolution of this Liberibacter lineage.To further understand Ca. Liberibacter capsica . In consequence, the evolutionary analyses presented here are conservative and are based only on Liberibacter homologs that are present in the Ca. Liberibacter capsica draft genome.The draft genome of capsica is simillturable . A total capsica , which i genomes . NeverthCa. L. capsica, Ca. L. asiaticus, Ca. L. psyllaurous, Ca. L. americanus, Ca. L. africanus, and L. crescens , and they were relatively short in amino acid length and annotated as hypothetical. Some of these hypothetical proteins occurred on contigs alone or with other Liberibacter orthologous proteins. The majority of novel orthologous clusters found in other Liberibacter species also were not associated with annotations based on Swiss-Prot, GO Terms, or the best BLAST hit based on the NCBI nr database. However, there were several cluster(s) identified in Ca. L. americanus (N = 1), Ca. L. asiaticus (N = 2), Ca. L. psyllaurous (N = 1), and L. crescens (N = 9) for which we could provide functional assignments based on Swiss-Prot (P16482) and NCBI BLASTP were annotated by Prokka as two proline/betaine (ProP) transporters and one glycine betaine/proline/ectoine/pipecolic acid transporter (OusA) , which consist of 443 single copy orthologs (Table S3), are shared among crescens . Approxicrescens . A totalectively . The 10 ignments . Liberib factors . In Ca. r (OusA) . Interesericanus .Ca. L. capsica were singletons and dS (synonymous substitutions per synonymous site) values among each species pair with our target species, Ca. L. capsica. For all 1:1 single copy orthologous pairs in which dS was not saturated, the dN/dS ratio was <1, indicating that purifying selection is widespread among Liberibacter single copy gene orthologs. For the species pair Ca. L. capsica and Ca. L. americanus, we found 439 gene pairs with an average dN/dS ratio of 0.13 (stdev = 0.08). A total of 365 gene pairs are under purifying selection between Ca. L. capsica and Ca. L. psyllaurous and had an average dN/dS ratio of 0.09 (stdev = 0.04). For the species pair Ca. L. capsica and Ca. L. asiaticus, we found 315 gene pairs with an average dN/dS ratio of 0.09 (stdev = 0.06), and for the species pair Ca. L. capsica and Ca. L. africanus, we found 285 gene pairs with an average dN/dS ratio of 0.09 (stdev = 0.04). For the most divergent species pair, Ca. L. capsica and Ca. L. crescens, although we found only 38 gene pairs that did not have saturated dS values, the average dN/dS ratio was still just 0.12 (stdev = 0.09). As expected, based on Swiss-Prot and GO term annotations, all gene pairs under purifying selection primarily represent housekeeping genes (Table S3).We analyzed the single copy orthologous genes (N = 443) that were found in all six Ca. L. capsica by analyzing ortholog pairs that represented the highest dN values (top 10%) for each pairwise comparison (N = 44) . Out of these Tad pilus proteins, CpaD was also in the top 10% of dN values for all Ca. L. capsica pairwise comparisons, except for that with its nearest relative, Ca. L. americanus (Table S4).We also identified the most divergent single copy orthologous proteins in (N = 44) . Within species . When co0% of dN ; Fig. S10% of dN . The Tade of DNA , 18. PhyPseudomonas aeruginosa . Currently, Russelliana capsici is the only known psyllid host of Ca. L. capsica. The psyllid R. capsica has been observed to feed on Capsicum annuum across its native distribution in Brazil and Argentina . As suchst plant .Ca. L. capsica\u2019s genome compared to the majority of Liberibacter taxa (Table S4). The Tad pilus complex is hypothesized to be important in the attachment and colonization of psyllid midguts because the Tad pilus genes are conserved in all Liberibacter taxa, and these Tad pilus genes are expressed more highly in psyllids compared to plants . Specifically, CpaC is the outer membrane secretin complex, and CpaD is linked to CpaC on the outer membrane and helps assemble CpaC that work together to form the Tad pilus complex are rapidly diverging in o plants . Recent o plants suggest ble CpaC , 25. As ribacter . It willCa. L. capsica, such as DegP and RseP, are important for a microbe\u2019s adaptation to the host environment because of their role in stress response. For example, DegP is a periplasmic serine protease that is essential for survival in high temperature environments compared to the Asian citrus psyllid (Diaphorina citri) to identify important protein candidates in Ca. L. capsica that may be involved in insect-plant interactions. Future research will extend the results from this study to further understand the genetics of Ca. L. capsica and, more broadly, the evolution of Liberibacter lineages.In summary, the draft genome of the new material , and we Ca. Liberibacter capsica was assembled previously in Kwak et al. (SRR15069915). To further refine and annotate metagenomic contigs identified in Kwak et al. using DIAMOND v.2.0.13 (Ca. L. capsica\u2019s genome were the following: (i) if the putative Ca. L. capsica protein\u2019s best hit was a Ca. Liberibacter species, this protein was binned as Ca. Liberibacter capsica; (ii) if the putative Ca. L. capsica protein\u2019s best hit was identified as a gene from a genus other than Liberibacter, it was further determined if this protein was surrounded by other Liberibacter proteins (based on BLASTP results) on the same contig. If surrounding proteins on the same contig were identified as Liberibacter proteins, then this protein was binned as Ca. Liberibacter capsica; and (iii) if the putative Ca. L. capsica protein was the only gene on a contig and had a best hit to a bacterium that belongs to Alphaproteobacteria with a percent identity less than 95%, it was binned as a Ca. Liberibacter capsica candidate gene. The final contigs that possessed proteins that were binned as Ca. Liberibacter capsica were submitted to NCBI genome as a draft Ca. Liberibacter capsica genome (accession number: JAMJGA000000000). Emboss 6.6.0 , Ca. L. psyllaurous (NC_014774), Ca. L. americanus (NC_022793.1), Ca. L. africanus (NZ_CP004021.1), and L. crescens (NZ_CP010522.1). For standardizing protein and nucleotide coding sequence data sets for the analysis of orthologous genes among the latter Liberibacter species, we used Prokka v1.14.5 (33) to identify and annotate proteins and nucleotide coding sequences for each Liberibacter and Ca. Liberbacter species. Orthologous clusters of proteins from Ca. L. capsica, Ca. L. asiaticus, Ca. L. psyllaurous, Ca. L. americanus, Ca. L. africanus, and L. crescens were determined using OrthoVenn2 , we calculated the nonsynonymous substitutions per nonsynonymous site (dN) and the synonymous substitutions per synonymous site (dS) for one-to-one coding sequence orthologs from OrthoVenn2 (To estimate the rates of molecular evolution between thoVenn2 . SimilarthoVenn2 , nucleotthoVenn2 . Then, athoVenn2 based onthoVenn2 . Gene paCa. Liberibacter capsica curated here was submitted to NCBI Genome under the accession number JAMJGA000000000. The raw metagenomic data of Ca. Liberibacter capsica can be found here (accession number: SRR15069915; [Ca. Liberibacter capsica are in Table S5 and Table S6, respectively.The draft genome assembly of"} +{"text": "Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.This study uses Machine Learning (ML) to classify subtypes of endocrine hypertension (EHT) in a large cohort of hypertensive patients using multidimensional omics analysis of plasma and urine samples. We measured 409 multi-omics (MOmics) features including plasma miRNAs (PmiRNA: 173), plasma catechol O-methylated metabolites (PMetas: 4), plasma steroids (PSteroids: 16), urinary steroid metabolites (USteroids: 27), and plasma small metabolites in primary hypertension (PHT) patients, EHT patients with either primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) or Cushing syndrome (CS) and normotensive volunteers (NV). Biomarker discovery involved selection of disease combination, outlier handling, feature reduction, 8 ML classifiers, class balancing and consideration of different age- and sex-based scenarios. Classifications were evaluated using balanced accuracy, sensitivity, specificity, AUC, F1, and Kappa score.Complete clinical and biological datasets were generated from 307 subjects . The random forest classifier provided \u223c92% balanced accuracy (\u223c11% improvement on the best mono-omics classifier), with 96% specificity and 0.95 AUC to distinguish one of the four conditions in multi-class ALL-ALL comparisons (PPGL vs PA vs CS vs PHT) on an unseen test set, using 57 MOmics features. For discrimination of EHT (PA\u00a0+\u00a0PPGL\u00a0+\u00a0CS) vs PHT, the simple logistic classifier achieved 0.96 AUC with 90% sensitivity, and \u223c86% specificity, using 37 MOmics features. One PmiRNA (hsa-miR-15a-5p) and two PSmallMB (C9 and PC ae C38:1) features were found to be most discriminating for all disease combinations. Overall, the MOmics-based classifiers were able to provide better classification performance in comparison to mono-omics classifiers.We have developed a ML pipeline to distinguish different EHT subtypes from PHT using multi-omics data. This innovative approach to stratification is an advancement towards the development of a diagnostic tool for EHT patients, significantly increasing testing throughput and accelerating administration of appropriate treatment.European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 633983, Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE (to Z.E. and F.B.), and Deutsche Forschungsgemeinschaft (CRC/Transregio 205/1). We searched PubMed from database inception to Jan 18, 2022, using the search terms ((machine learning) OR ) AND OR (pheochromocytoma) OR (paraganglioma) OR (Cushing's syndrome) OR (endocrine hypertension) OR (hypertension)) AND (Multi-omics), with no language restrictions. Our search yielded 10 results. Three articles reviewed the use of artificial intelligence in cardiovascular medicine and hepatology. Although one similar review article focussed on primary hypertension, however, it did not include any multi-omics based study on hypertension. Five research articles used machine learning in conjunction with multi-omics for major heart diseases, intraocular pressure and metabolic syndrome. One of the articles studied heart failure in rats. No articles using multi-omics data with machine learning for stratifying endocrine hypertension patients were found.To the best of our knowledge, this is the first-ever study to investigate machine learning-based classification of endocrine hypertension subtypes using multi-omics data. This large retrospective study included patients from 11 reference centres for endocrine hypertension with access to a complete set of biosamples, and multi-centre omics measurements. Our machine learning pipeline enabled the classification of 5 disease combinations using 8 supervised ML classifiers and to discover the best discriminating features. This approach outperformed the individual omics models when used for stratifying hypertensive subtypes in a multi-class scenario.Our multi-omics based machine learning approach to stratification is an advancement towards the development of an innovative tool in the diagnosis of hypertensive patients in clinical practice, greatly increasing throughput and accelerating the administration of appropriate treatment. It will also help identification of previously unsuspected molecules as biomarkers of complex, chronic diseases. The effect of this approach in clinical practice will be further tested in a prospective study and in a randomised controlled trial.Alt-text: Unlabelled box,Arterial hypertension is one of the major chronic diseases leading to high morbidity and mortality worldwide.The majority of cases are classified as \u2018primary\u2019 hypertension (PHT). PHT is a multifactorial and complex disease with causes and contributing factors still incompletely understood. A combination of genetic and socio-environmental risk factors including salt intake, obesity, alcohol consumption, chronic stress, and urbanisation have been associated with PHT.,Exclusion of secondary hypertension including EHT is necessary to diagnose PHT. This usually entails lengthy evaluation involving blood and urinary tests, imaging procedures and eventually invasive testing.,Over the past two decades, there have been significant advances in various omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics.The primary purpose of this study was to train Machine Learning (ML) algorithms for diagnosing endocrine hypertension subtypes using MOmics data. It also aims to provide an understanding of discriminating features and their importance to different disease combinations.Retrospective plasma and 24h urine samples from patients with PA, PPGL, and CS were provided by 11 collaborating reference centres for endocrine hypertension that were participants of the ENS@T-HT Horizon2020 consortium.All study protocols under which patients were recruited were approved by the local ethics committee at CPP Ile de France II (2012-A00508-35), Comit\u00e9 de Protection des Personnes Ile de France 4 (2015/63NICB), Technische Universit\u00e4t Dresden Ethikkommission (189062010/EK7122010), Munich: Ethikkommission der LMU M\u00fcnchen (379-10), Zurich: Kantonale Ethikkommission des Kanton Z\u00fcrich (2017-00771), University of W\u00fcrzburg (88/11), University Hospital Galway (C.A. 1082), Comitato Etico per la Sperimentazione Clinica della Provincia di Padova (3998/AO/16), Comitato Etico Interaziendale AOU Citt\u00e0 della Salute e della Scienza di Torino - AO Ordine Mauriziano di Torino- A.S.L. TO1 (Prot. 0000759 Pratica CS2/112), Medisch-ethische toetsings commissie Oost-Nederland (N157215.091.1.6), National Institute of Cardiology, Warsaw, Poland (1233/2010), West Ethics Committee, Western Infirmary, Glasgow (AHT/JR) and MVLS College Ethics Committee, University of Glasgow . All subjects provided written informed consent before participation in protocols.The biosamples were provided to 5 omics data-generating collaborators of the ENS@T-HT Horizon2020 project (Appendix Table 1). These omics included PmiRNA, PMetas, PSteroids, USteroids, and PSmallMB. The details are as follows:Levels of 179 human miRNAs were measured in plasma after extraction of total RNA from 200\u00a0\u00b5L EDTA-plasma using the miRNeasy Mini kit . 4\u00a0\u00b5L of undiluted RNA was then reverse-transcribed to cDNA in a 20\u00a0\u00b5L reaction volume using the Universal cDNA synthesis kit II . Selected plasma miRNAs were quantified using Serum/Plasma Focus microRNA PCR Panels according to their standard protocol, in combination with ExiLENT SYBR\u00ae Green master mix (Exiqon) and ROX solution on a Quantstudio 12K Flex Real-time PCR System (Thermo Fisher). Raw data generated by the QuantStudio System were analysed using GenEx software . Quality controls all along the procedure were performed using different spike-in RNAs and cDNAs. Data normalisation was performed using the five miRNAs most stably-expressed across the dataset, as identified by Normfinder software;,Plasma free metanephrines, normetanephrine and metanephrine, and 3-methoxytyramine, the O-methylated metabolites of norepinephrine, epinephrine and dopamine, respectively, were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS), as described elsewhere.Sixteen plasma steroid hormone profiles (See Appendix Table 2) were analysed by LC-MS/MS as described elsewhere.,Twenty-seven urinary steroid metabolites derived from glucocorticoid, mineralocorticoid and androgen biosynthesis as well as core steroid precursors were measured using multi-steroid profiling by LC-MS/MS. A description of this methodology has been published previously.IDQTM p180 Kit . The assay allows the simultaneous quantification of 188 metabolites out of 10\u00a0\u00b5L plasma. The assay procedures of the AbsoluteIDQTM p180 Kit, as well as the metabolite nomenclature, have been described in detail previously.32The targeted metabolomics approach was based on LC-MS/MS measurements using the AbsoluteAll the omics data was catalogued in RDMPThe biomarker discovery involved the selection of disease combinations, outlier detection, choice of supervised ML classifiers, configuration of experiment parameters, and consideration of different evaluation scenarios .Figure 1training dataset: The sample of data used to fit the model, (b) validation dataset: The sample of data used to validate the trained models during the 100 random repeats and (c) test dataset: The independent samples of \u2018unseen\u2019 data used to test the final trained model.The supervised machine learning used non-overlapping training, validation and test datasets. These can be defined as: (a) The MOmics and mono-omics datasets were once randomly split into training (\u223c80%) and testing (\u223c20%) set (Appendix Table 4). The training set was then further split into training-validation (80\u201320%) split for 100 Random Repeats (RR) using random seed for each iteration to ensure reproducibility. Finally, the test set was only used for independent validation of the final trained model and not used during any model training.The five different disease combinations used for classification were: ALL-ALL (PPGL vs PA vs CS vs PHT), EHT (PPGL+PA+CS)-PHT, and each individual endocrine hypertension -PHT. These combinations did not include NV since the key question addressed was: How can hypertensive patients be stratified amongst themselves? Omics data from NV was used to compare individual biomarkers with patients of different hypertension types. This data was not used for any model development or testing.To study the impact of outliers on classification, two sets of results were analysed, as shown in Stage 1 i.e., 1)An assorted set of 8 different classifiers: Decision Trees (J48),One of the key objectives of the analysis was to identify the list of most discriminating features for a given disease combination. Possible bias due to the age or sex of the patients was studied with different sets of scenarios. Stage 3 of the schematic shows the steps for the final/testing stage using original test data . The omiThe funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report and decision to submit the paper for publication.The study included 487 patients with PA, PPGL, CS and PHT as well as normotensive volunteers (NV) , who were recruited by reference centres for adrenal disorders of the ENS@T-HT Horizon2020 consortium.The biomarker discovery comprised three stages : a pre-pFirst, the classification performance for ALL-ALL using MOmics data excluding and including outliers was evaluated . Excluding outliers provided better classification as observed from various performance metrics. SL provided \u223c4%, 5%, and 1% increases in balanced accuracy, sensitivity, and specificity when excluding outliers, respectively. Overall, LB, SL, and RF were the best performing classifiers. Next, feature selection methods were compared using LB, RF, and SL classifiers for ALL-ALL disease combination . Both filter and wrapper methods provided comparable classification performance. However, wrapper method was chosen for next stages of analysis since it evaluates the feature subsets as search problem to find key dependencies amongst features.The top 3 ML models were trained using the reduced training dataset which used top features from 100 RR for each disease combination , F1, and Kappa score a. Using For the EHT-PHT combination, the SL classifier with MOmics provided 0.96 AUC c with 90For the PA-PHT combination, the SL classifier using MOmics provided highest balanced accuracy and AUC (\u223c90% and 0.95 respectively) with 95% sensitivity and \u223c86% specificity a and c. These classifiers were also tested on the training dataset to understand the effect of overfitting (Appendix Table 6-10). Amongst the three classifiers , evidently RF provided superior classification results when tested on the training set in comparison to the testing set. This highlighted the overfitted training of the RF classifier irrespective of whether the training data was balanced or not. On the other hand, LB and SL classifiers were less overfitted and performed consistently for both training and testing set.The final selected set of MOmics features used for classifier training comprised different omics features for each disease combination. The PmiRNA and PSmallMB features represent 88% of the whole MOmics dataset a, a simiThe commonality of selected MOmics features amongst different disease combinations was also investigated c. Two PSThe discriminating features selected for mono-omics classifiers were also examined d. Age anThe contribution of each omic in the final selected MOmics features (with regard to the count in the whole dataset) was also analysed. For example, 3 out of 4 PMetas features (75%) were selected in ALL\u2013ALL and PPGL-PHT disease combinations. None of the PSteroids features was selected in PPGL-PHT. No PMetas were selected in PA-PHT and CS-PHT combinations d.The close examination of features amongst MOmics and mono-omics classifiers highlighted that all the features selected in MOmics were part of the individual omics classifiers, except PSmallMB and PmiRNA d. In casThe MOmics features selected in ALL-ALL disease combination were compared with corresponding omic features for NV in the training set . Also, Principal Component Analysis was conducted for all five disease combinations alongside NV . The first component of ALL-ALL and EHT-PHT accounted for \u223c40% and 57% of the explained variance respectively.The training set of the MOmics data was studied for a different set of scenarios . These sFor Scenario 1, MOmics data provided better performance for all disease combinations . In intra-set comparison, MOmics achieved similar performance in Sets A and B across all disease combinations. Hence, excluding age and sex (in Set B) as features did not materially alter the performance of the classification. However, for PMetas, balanced accuracy dropped when age and sex were excluded (Set B) from the feature set (except for PPGL-PHT). For example, balanced accuracy was down by 5% and 7% for ALL-ALL and EHT-PHT respectively.The remaining four mono-omics provided comparable performance irrespective of age and sex being used as features. For example, in the case of USteroids, the detailed summary of features selected during the 100 RR show that almost the same features are selected approximately equal number of times for Set A and B . Similar trends were observed for other mono-omics . Notably, for MOmics despite including age and sex as features (Set A), the selection frequencies were below the threshold in 100 RR and therefore they were not designated as top features .The classification performance of Sets C and D was not comparable since they used different numbers of samples for training and testing. However, it is noticeable that the female subset provided better accuracy for EHT-PHT and PA-PHT in comparison to male subset for MOmics data . The intra-set comparison highlighted the superior performance of MOmics dataset for ALL-ALL and EHT-PHT disease combinations in comparison to mono-omics irrespective of classifier selection. For PPGL-PHT, PMetas outperformed the MOmics classification for both the Sets. However, in case of CS-PHT, Set C could not be run due to an insufficient number of male CS samples for classifier training (Appendix Table 4).From the perspective of feature selection, in the MOmics dataset, different features were selected for Sets C and D . For example, in ALL-ALL, O1_hsa-miR-15a-5p, O5_Spermidine and O5_Spermidine/Putrescine were only selected for male dataset. On the contrary, various other features such as O5_PC ae C38:1, O3_18oxo-Cortisol, and O4_18-OHF were only selected for female dataset. On close examination, it was evident that the union of Set C and Set D features approximately intersect with both Sets A and B. Similar trends were also observed across most of the disease combinations in MOmics and mono-omics datasets .Overall, MOmics data provided better classification performance in comparison to mono-omics (except PPGL-PHT), irrespective of the cohort age . When considering the inter-set comparison, Set E (age >= 50) provided better results than Set F (age < 50) for almost all disease combinations. A higher number of unique features were selected for both the cohorts for all disease combinations . Similar trends were noticed for mono-omics datasets .This study investigates MOmics ML integration for stratification of arterial hypertension. Our results show that the MOmics approach provided improved discriminatory power in comparison to single omics (mono-omics) data analysis and was able to correctly identify different forms of endocrine hypertension with high sensitivity and specificity, providing potential diagnostic biomarker combinations for diagnosing hypertension subtypes. In particular, it was able to classify subtypes of hypertension with 96% specificity and 0.95 AUC in the ALL vs ALL disease combination, achieving \u223c11% improvement in balanced accuracy on an unseen test set in comparison to the best performing mono-omics classifier using a reduced set of 57 features. The feature set had distinct characteristics when compared with normotensive volunteers and hence can be potentially utilised as biomarker in clinical application.,With the availability of recent high-throughput experimental and computational technologies, ML-based integration will facilitate the discovery of biomarkers for diagnosis and improve the understanding of complex diseases such as arterial hypertension. However, obtaining MOmics data can be logistically challenging when biosamples are sourced from multiple recruitment sites and require multi-centre omics measurements. This can lead to fewer samples with all available omics for integration. The ENS@T-HT study, by obtaining a complete set of omics for \u223c84% of the total patients, provided a straightforward example that this challenge can be successfully addressed. Although a few mono-omics studies on identification of endocrine forms of hypertension have been published,This study predicted EHT subtypes using a dedicated and customisable ML pipeline. The imbalance of classes is a well-known problem in ML which does not allow the classifier to learn from the minority class. This was corrected for CS and PPGL patients with the use of Synthetic Minority Over-sampling TEchnique.Despite the strong classification performance, the analysis had a few shortcomings. Firstly, since CS is a rare disease, samples for CS patients were limited. Secondly, advanced ML techniques such as deep learning could not be used for this analysis as they require a much larger number of samples than was available in this study. Finally, all the samples could not be used for MOmics integration because of limitations in sample volume or specific quality measures, which is a common problem for a study with multi-site biosamples and multi-centre omics measurement. However, a major strength of this study was to rely on unambiguous diagnosis of the major subtypes of EHT according to guidelines by expert centres. In addition, our analysis only explored the MOmics data using a ML based data-driven approach. The discovered top discriminating features need further investigation in terms of biological significance and pathway network analysis.This study provided a valuable insight into a complex multi-class problem of endocrine hypertension stratification. It uses multi-omics data and evaluated its superior performance in comparison to mono-omics. Although internal validation was conducted using an unseen test set, further validation on external cohorts before any translation in clinical setting will be valuable. The ENS@T-HT study is currently capturing data from a wider population in a prospective manner to measure the most discriminating features of the new samples and perform independent validation .This would allow the classifier to become more robust and well-trained for a formal clinical deployment. The refined algorithm could be deployed as a webserver-based classification tool and utilised to screen patients at primary care to refer patients identified as being at risk of endocrine hypertension to centres with appropriate expertise for subsequent evaluation if required. The developed ML pipeline is fully customisable and can be deployed for other mono/MOmics data- based biomarker discovery and analysis studies. For example, it can be used to investigate MOmics signatures for other forms of secondary hypertension such as renal artery stenosis.To conclude, in this study we have developed an innovative approach to predict different subtypes of arterial hypertension using multi-omics data. A machine learning pipeline using 5 disease combinations and 8 supervised ML classifiers was introduced and scenarios evaluated based on age and sex bifurcation. The ML pipeline provided promising classification outcomes and the reduced features have the potential to further contribute as clinical biomarkers for detecting hypertension subtypes. This is expected to improve stratification of patients with hypertension for implementation of targeted treatment and prevention of cardiovascular complications.All authors read and approved the final version of the manuscript. M-C.Z., E.J., E.D. and P.S.R. conceived and designed the study. P.S.R. and S.Reel developed and implemented ML pipeline under the supervision of E.J.. J.C.v.K, K.Lang, C.K.L., C.Pamporaki, S.M.M., A.E.T., M.P., J.D.M, C.Prehn, J.A., G.E., E.D. developed the methodology for omics data generation. J.C.v.K., S.Robertson, S.M.M., J.D.M. and A.R. used GENEX software for miRNA data. T.N. and A.S. developed software for cataloguing the omics (RDMP) and phenotypic data (ENSAT-HT registry) respectively. P.S.R., S.Reel, J.C.v.K., K.Lang, C.K.L., S.Robertson, S.M.M., A.E.T., M.P., J.D.M., A.R., C.Prehn, J.A., M-C.Z., E.D. and E.J. validated the various phases of the study. J.C.v.K., K.Langton, K.Lang, Z.E., C.K.L., C.Pamporaki, S.Robertson, A.E.T., M.P., J.D.M., A.R., C.Prehn, J.A. and E.D. performed formal analysis and investigation on omics data. K.Langton, Z.E., L.A., C.Pamporaki, P.M., A.B., M.Kabat, M.P., F.C., C.S., M.R., M.Kroiss, M.C.D., A.Pecori, S.M., J.D., G.P.R., L.L., I.S., A-P.G-R., G.A., F.B., G.E. and E.D. provided resources such as bio-samples for omics data. P.S.R., S.Reel, K.Langton, K.Lang, Z.E., C.Pamporaki, M.P., W.A.and G.E. curated the omics data. P.S.R, M-C.Z. and E.J. verified the data. P.S.R. and S.Reel wrote the initial draft of the manuscript with assistance from M-C.Z. and E.J. The details of methodology of omics data generation was provided by Z.E., S. Robertson, S.M.M., M.P., W.A., G.E., E.D. and M-C.Z.. The following drafts were reviewed and edited by P.S.R., S.Reel, Z.E., L.A., P.M., A.B., S.Robertson, S.M.M., M.P., M.R., M.Kroiss, J.D., G.P.R., L.L., J.D.M., A.R., C.C., W.A., F.B., G.E., E.D.,M-C.Z. and E.J.. P.S.R. and S.Reel drafted the data visualisations. S.M.M., W.A., G.E., E.D., M-C.Z. and E.J. supervised the study. P.S.R., L.A., P.M., A.B., S.M.M., W.A., F.B., G.E., E.D., M-C.Z. and E.J. were involved in the planning and execution of this study. L.A., P.M., S.M.M., M.R., J.D., G.P.R., J.D.M., W.A., F.B., G.E., E.D., M-C.Z. and E.J. acquired the financial support for the ENSAT-HT project leading to the work in this manuscript.https://doi.org/10.5281/zenodo.7033087).The data related to the results presented in this article can be obtained upon reasonable request. The data can be made available to the researchers who provide a methodologically sound proposal, subject to ENSAT-HT executive committee's approval (which includes representatives of the biosamples collections and omics data generation centres). The researcher would need to complete a Data Sharing Agreement. All requests should be directed by email to the corresponding author. The study used well-established computational packages and libraries as referenced in the Methods section. The codebase used in this study is available online (P.S.R., S.Reel, K.Lang, A.E.T., M.R., W.A., F.B., G.E., M-C.Z. and E.J. are listed as co-inventors on patents filed related to Biomarkers for Diagnosis and Treatment of Endocrine Hypertension, and Methods of Identification thereof.P.S.R., S.R., J.C.v.K., K.Langton, K.Lang, Z.E., C.K.L., L.A., P.M., A.B., M.Kabat, S.Robertson, S.M.M., A.E.T., M.P., F.C., M.Kroiss, M.C.D., S.M., J.D., G.P.R., L.L., J.D.M., A.R., A.S., I.S., J.A., A-P.G-R., G.A., W.A., F.B., G.E., E.D., M-C.Z. and E.J.reports grants from European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 633983, during the conduct of the studyK. Langton reports grants from CRC/TRR 205 Project B 15 and Patient Cohorts and Biobanks Fonds 041_526513, outside the submitted work. P.M. reports personal fees from DIASORIN, outside the submitted work. J.D. reports grants from Idorsia and Damian Pharma, outside the submitted work. G.E. reports grant from DFG, outside the submitted work.The other authors declare no conflict of interest."} +{"text": "Tomato Solanum lycopersicum L. is one of the main vegetable crops, accessions and cultivars of which are characterized by a low level of genomic polymorphism. Introgressive tomato breeding uses related wild Solanum species to improve cultivars for stress tolerance and fruit quality traits. The aim of this work was to evaluate the genome variability of 59 cultivars and perspective breeding lines of S. lycopersicum and 11 wild tomato species using the AFLP method. According to the AFLP analysis, four combinations of primers E32/M59, E32/M57, E38/M57, and E41/M59, which had the highest PIC (polymorphism information content) values, were selected. In the process of genotyping a collection of 59 cultivars/lines of S. lycopersicum and 11 wild tomato accessions, the selected primers revealed 391 fragments ranging in size from 80 to 450 bp, of which 114 fragments turned out to be polymorphic and 25 were unique. Analysis of the amplif ication spectra placed wild tomato accessions into separate clades. Sister clades included cultivars of FSCV breeding resistant to drought and/or cold and, in part, to late blight, Alternaria, Septoria, tobacco mosaic virus and blossom end rot, as well as tomato accessions not characterized according to these traits, which suggests that they have resistance to stress factors. In accessions of distant clades, there was clustering on the basis of resistance to Verticillium, cladosporiosis, Fusarium, tobacco mosaic virus, gray rot, and blossom end rot. The combination of ac cessions according to their origin from the originating organization was shown. The primer combinations E32/M59,E32/M57, E38/M57 and E41/M59 were shown to be perspective for genotyping tomato cultivars to select donors ofresistance to various stress factors. The clade-specif ic fragments identif ied in this work can become the basis for thedevelopment of AFLP markers for traits of resistance to stress factors. The assessment of genetic diversity, considering the pedigreesof crop cultivars and associations with important traits, is oneof the foundations of modern breeding. Various methods ofmolecular genome analysis are used in the selection of parentalgenotypes, as well as in identifying the level of variability bothwithin a variety and between varieties . Both the entire plant genome andits particular regions are subjected to DNA genotyping. Polymorphism dataare used, for example, to develop molecular DNA markerslinked to important traits. Markers are used to search for donorsof the corresponding genotypes, as well as to certify varietiesand lines .One of the commonly used methods for assessing plantgenome variability is the AFLP (Amplified Fragment LengthPolymorphism), which is based on the assessment of uniqueand moderately repetitive genome sequences, but does notrequire the determination of the sequences themselves . The evaluationis based on selective PCR amplification of restrictionfragments from a total genomic DNA digest .The use of AFLP markers is applicable to all species, highlyreproducible, and highly efficient in determining genetic distancesand phylogenetic relationships in taxonomy . The methodhas been successfully applied to study wild and endangeredplant species . Inaddition, AFLP is popular in modern plant breeding and isused to determine pedigrees, variability, homogeneity, and thedegree of introgression and hybridity of varieties, as well asto search for molecular markers associated with economicallyvaluable traits . Such studies have been carried out, for example,on wheat , barley ,peas , pepper and potato .The AFLP has also been used for genotyping tomato (Solanumlycopersicum L.). Thus, with this method, an intraspecificmap of the tomato genome was obtained , the transcriptional response of tomato to nematodeinfection was studied , and DNAmarkers linked to resistance to tomato bacterial wilt and cladosporiosis wereidentified. The use of AFLP for comparing the response ofheat-tolerant and heat-sensitive tomato genotypes to moderateheat stress conditions revealed a number of differentiallyexpressed constitutive genes, presumably determining heattolerance and differences in genotype adaptation to elevatedtemperatures .The phylogenetics and genogeography of crop wild relativesare effective approaches to understanding their evolutionarypatterns and unlocking their potential to improve crops. AFLPgenotyping against geographic and climatic indicators hascontributed to the study of the spatial genetics of wild tomatospecies S. lycopersicum, S. pimpinellifolium and S. peruvianum . TheS. lycopersicum and S. pimpinellifolium evolutionary patterns,including demographic history, dispersal patterns, interspecificdivergence and hybridization, have been shown to be closelyrelated to the complex geographic and ecological conditionsin the Andes . An AFLP studyof 19 natural populations of S. peruvianum revealed a moderatedegree of population differentiation, probably reflectingpartial geographic isolation between tomato species .In addition to solving taxonomic and phylogenetic problems,the AFLP method is used to determine the variabilityof tomato varieties. Various DNA marking systems showedlow efficiency for studying the genetic diversity of tomatocultivars with limited genetic variability. The use of AFLPin combination with SSR markers to characterize 48 closelyrelated Spanish tomato varieties made it possible to obtain aunique fingerprint for each analyzed accession .Cultivated varieties and lines of tomato belong to the speciesS. lycopersicum. Compared to wild related species (sectionLycopersicon of the genus Solanum) , theirgenomes are significantly less polymorphic (20 or more times). Hundreds of genes and loci of quantitative traits linkedto resistance, yield, flower and fruit characteristics, and plantarchitecture have been mapped in the genome of wild species. Due to the relative ease of crossing withS. lycopersicum, wild species are actively used in introgressivetomato breeding to improve economic traits associated withstress resistance, yield and quality . For example, sources of varyingdegrees of resistance to bacterial wilt are L. pimpinellifolium(= S. pimpinellifolium) PI127805A, L. esculentum var. cerasiforme(= S. lycopersicum var. cerasiforme) CRA66, L. pimpinellifoliumPI129080 and L. esculentum AS52 . In cultivars with purple fruits, the trait of anthocyaninbiosynthesis in the fruit was obtained by introgression from the genomes of wild species S. chilense and S. cheesmaniae.Thus, the low level of genomic polymorphism of tomatovarieties is combined with introgressive genes/loci associatedwith economically valuable traits. Therefore, multilocusgenome mapping methods can presumably separate cultivarsaccording to useful traits.Despite the importance of varietal certification and assessmentof intervarietal genome variability, there are few studieson marking the genotypes of tomato cultivars in Russia, andthese are mainly works on genotyping using already knownmarkers . For example, a collection of tomatovarieties and hybrids from the Michurinsky State AgrarianUniversity was screened using the P7 molecular markerto identify donors of cladosporiosis resistance .In this study, using the AFLP method, we assessed thegenomic variability of tomato S. lycopersicum cultivars andlines of domestic and foreign breeding from the collection ofthe Federal Scientific Vegetable Center (FSVC) in comparisonwith wild accessions of tomato species.For the study, 59 tomato S. lycopersicum cultivars and perspectivebreeding lines of domestic and foreign breeding fromthe FSVC collection were selected (Table 1). 11 wild tomatospecies were used as an outgroup (see Table 1). 34 varietiesof the sample (~58 %) are included in the State Register ofBreeding Achievements Approved for Use of the RussianFederation for 2022 (https://reestr.gossortrf.ru/). Seeds ofaccessions were germinated under standard greenhouse conditions. Genomic DNA wasisolated from freshly harvested 5\u20136 day old seedlings usingthe CTAB method .Data on drought and cold resistance, resistance and susceptibilityto diseases were partially taken from the StateRegister of Breeding Achievements (http://reestr.gossortrf.ru/), as well as kindly provided by the originators of the varietiesand Ph.D. I.A. Engalycheva.AFLP analysis was carried out according to the standardprotocol: hydrolysis of 350 ng of genomic DNA of each accessionwith restriction enzymes EcoRI and MseI followedby ligation with EcoRI and MseI adapters .Selective amplification was performed in two stages: (1) preamplification withadapter primers EcoRI+1 and MseI+1 withone selective nucleotide (A) at the 3\u2032 end; (2) amplificationwith primers EcoRI+3 and MseI+3 with three selective nucleotidesat the 3\u2032 end. The results were visualized in a denaturing6 % polyacrylamide gel using a LI-COR 4300 gel analyzer. The experimentwas carried out in one repeat for each combination of primers.The polymorphic information content (PIC) index for eachprimer combination was calculated according to Botstein etal. (1980) and Krishnamurthy et al. (2015).Molecular panels of AFLP fragments were documented inthe form of binary matrices (Excel program). Based on theconstructed spectra and matrices, variety-specific DNA markerswere identified, coefficients of pairwise genetic similarity/difference between accessions (GS) and genetic distances(GD = 1 \u2013 GS) were calculated, cluster analysis was performed and groups of genetically similar accessions were determined(PAST software package) .Analysis of the genomic structure of the population of thestudied accessions was carried out using the Structure v.2.3.4,which makes it possible to identify common genetic blocksand their ratio in each accession .Since up to 80 % of the standard AFLP spectrum can serve asmarkers for the detection of genetic polymorphisms, and theeffectiveness of AFLP depends on primer combinations , primer/enzyme combinations were selected andtested for multilocus AFLP analysis of tomato accessions.On a sample of five tomato accessions, seven combinationsof primers EcoRI+3/MseI+3 were tested, differing in thecomposition of selective nucleotides at the 3\u2032 end: E32/M59(E-AAC/M-CTA); E32/M57 (E-AAC/M-CGG); E38/M57(E-ACT/M-CGG); E41/M59 (E-AGG/M-CTA); E32/M61(E-AAC/M-CTG); E38/M47 (E-ACT/M-CAA); E38/M59(E-ACT/M-CTA). It was shown that the use of combinationsof E32/M59, E32/M57, E38/M57 and E41/M59 givesa polymorphic, well-differentiated spectrum with an optimalnumber of fragments.Four selected primer combinations were used to label59 S. lycopersicum cultivars/lines and 11 wild tomato accessions.As a result, 391 fragments 80\u2013450 bp in size weredetected, of which 114 (29.2 %) fragments turned out to bepolymorphic (Table 2). The primer combination E41/M59was the most effective: 47 out of 67 obtained fragmentswere variable. At the same time, the E32/M59 combinationcorresponded to the largest number of fragments unique forindividual accessions (11 out of 25 found) (see Table 2). Incase of the combinations E32/M61, E38/M47, and E38/M59no polymorphic and unique fragments were identified.The PIC value ranged from 0.367 (E32/M57) to 0.658 (E41/M59) (see Table 2) with a mean value of 0.504, indicatingthat a large number of polymorphisms can be detected usingthe E41/M59 primer pair.Based on the results of the AFLP analysis, a dendrogramthat clearly divided the tomato accessions into clusters I and IIwas constructed .Wild tomato accessions were grouped into two clades ofcluster I: accessions 1 to 7 (including representatives of wildtomato species and a wild accession of S. lycopersicum) wereseparated into clade A; accessions 8\u201311, including wild accessionsof cultivated species fell into clade C. Clade C was sister to clade B, consistingof seven S. lycopersicum cultivars . Clade D (intermediate positionbetween A and B+C) combined 14 tomato varieties/lines.The two clades of cluster II, in turn, were divided into twosubclades each .On the graph constructed by the method of principal components,the analyzed cultivars formed three diffuse pools ofgenotypes, where, as in the dendrogram, a group of wild accessionsstood out, and tomato varieties/lines were clusteredin a similar way . There was a clear division betweenclusters I and II (according to the dendrogram). Wild accession11 (S. lycopersicum var. pyriforme) was the closest tosubclade B varieties/lines.It was interesting to analyze the possible relationshipbetween the clustering of cultivars and accessions obtainedfrom AFLP data and resistance to various biotic and abioticstresses.Varieties/lines of tomato included in cluster I are the result of breeding by the FSVC (except accession 34).All of them are resistant to cold and/or drought, while accession34 is susceptible. A similar situation is observed in thecase of resistance to blossom end rot, Septoria and Alternaria.All clade B accessions are resistant to tobacco mosaic virus, asare half of clade D accessions .Six accessions of clade D and five accessions of clade B are resistant to late blight; the remaining accessions of these cladesare susceptible to this diseaseAccessions of subclades E and H, with the exception ofone uncharacterized accession (62), are characterized by resistanceto cold and drought; in subclades F and G, four andthree accessions are resistant, respectively. Subclades E and Fare distinguished by resistance to blossom end rot, gray moldand cladosporiosis (except for single susceptible or uncharacterizedvarieties). About half of subclade E accessions areresistant to Verticillium and Fusarium. Most of subclade H accessions,as well as two groups of the subclade F, are resistantto Fusarium. Subclade G accessions have resistance to lateblight . Almost all subclade H accessions originatedfrom the FSVC. Accessions of foreign breeding (except for 55and 40) stand out in subclade F, clustering together with accessionsof breeding of LLC \u2018Breeding company GAVRISH\u2019.The study also included an analysis of the population structureof 70 tomato accessions, which revealed common geneticblocks and their ratio in each accession. This distributed theanalyzed accessions into clusters. In total, 16 options for thenumber of subgroups (k) from 3 to 18 were analyzed. The bestresult (LnLike = \u201312363.6) was obtained for k = 3.On the graph, the genomic structure of the studied 70 tomatoaccessions is presented in the form of various ratios of threeblocks . All accessions of wild species, including accessionsof S. lycopersicum, fell into cluster II. An analysisof the correlations between the distribution of accessions byclusters and the traits under consideration (see Table 1) showeda tendency to combine accessions in terms of resistance to grayrot, blossom end rot, Fusarium, cladosporiosis, and Septoria(cluster I). Cold and drought resistant accessions are presentedin large numbers in all three clusters. Resistance to Alternaria,Septoria, and TMV proved to be the most typical for cluster II. Also, half of the varieties in cluster II are resistantto blossom end rot, and a third of the accessions are resistantto late blight. Cluster III accessions were characterized bydifferent variants of resistance; we can assume clusteringon the basis of resistance to TMV (11 out of 16 accessions),as well as susceptibility to gray rot. Except for accession 40(cluster III), all tomato accessions of foreign breeding wereidentified in cluster I. The accessions of the LLC \u2018Breedingcompany GAVRISH\u2019 were distributed similarly .In this study, using the AFLP method, we analyzed 11 wild and59 cultivated (S. lycopersicum) tomato accessions, mainly ofdomestic breeding (see Table 1). It should be noted that dataon resistance to various diseases are unknown for some analyzed cultivated and wild accessionsstudied. The species S. lycopersicum (wild accessions 7\u201311in Table 1) comes from the humid tropics of South Americaand is a classic example of a cold-sensitive crop .The remaining wild species used (accessions 1\u20136 in Table 1)grow in different climatic zones of South America, from thetropics of the Amazon basin to deserts along the coast and thecold high mountains of the Andes . Thissuggests that accessions 1\u20136 are resistant to cold and drought,and accessions 7\u201311 are sensitive to these stresses.Each of the 70 accessions was characterized by a specificrange of fragments obtained using a combination of fourprimer pairs (see Table 2). The efficiency obtained was comparablewith the results of other studies. For example, an AFLPanalysis of 21 tomato varieties with four primer combinationsrevealed 298 fragments, including 159 polymorphs . The percentage of polymorphicfragments obtained by us (29.16 %) also fit into the knowndata on different crops \u2013 in a number of studies it varies from17.4 to 78.3 % .Analysis of the obtained AFLP data using various bioinformaticmethods distributed the studied tomato accessions ina similar way . Wild tomato accessions isolatedthemselves into a separate group or divided intoclades within cluster I . In the dendrogram, accessions1\u20136 (tomato species except S. lycopersicum) constituteda separate clade A, and 8\u201311 (various wild S. lycopersicumaccessions) constituted clade C . At the same time,accession 7 (S. lycopersicum LA1673) did not combine with8\u201311, but entered the subclade with red-fruited accessions 3\u20136, which may indicatea probable interspecific introgression. Sister clades B and Dconsisted of S. lycopersicum cultivars, for which resistance todrought and/or cold was shown . This, on the onehand, confirms our assumptions about the possible resistanceof wild accessions 1\u20136 taken for analysis to drought/cold, andalso suggests this trait in accessions 7\u201311. Cold/drought resistancein more than half of the samples of clusters I and II allows us to assume the presence of such resistance invarieties for which there are no data. In addition, the resultsmay indicate the presence of traits of resistance to abioticstresses introgressed from wild tomato species in the genomeof varieties of both clusters.A fairly clear grouping of accessions by origin shows theeffectiveness of the analysis and, at the same time, helps totrace possible links in the pedigree of varieties both from oneoriginator and between breeding centersThus, using AFLP genotyping of selectively neutral regionsof the genome of S. lycopersicum cultivars/lines and wildtomato species, clustering of accessions was shown accordingto resistance to biotic and abiotic stress factors, as wellas according to origin from different breeding centers. 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Genetic enhancement of fruit quality is a fundamental goal of pear breeding programs. The genetic control of pear fruit quality traits is highly quantitative, and development of high-density genetic maps can facilitate fine-mapping of quantitative trait loci (QTLs) and gene identification. Bin-mapping is a powerful method of constructing high-resolution genetic maps from large-scale genotyping datasets. We performed whole-genome sequencing of pear cultivars \u2018Niitaka\u2019 and \u2018Hongxiangsu\u2019 and their 176 F1 progeny to identify genome-wide single-nucleotide polymorphism (SNP) markers for constructing a high-density bin-map of pear. This analysis yielded a total of 1.93 million SNPs and a genetic bin-map of 3190 markers spanning 1358.5\u00a0cM, with an average adjacent interval of 0.43\u00a0cM. This bin-map, along with other high-density genetic maps in pear, improved the reference genome assembly from 75.5 to 83.7% by re-anchoring the scaffolds. A quantitative genetic analysis identified 148 QTLs for 18 fruit-related traits; among them, QTLs for stone cell content, several key monosaccharides, and fruit pulp acids were identified for the first time in pear. A gene expression analysis of six pear cultivars identified 399 candidates in the identified QTL regions, which showed expression specific to fruit developmental stages in pear. Finally, we confirmed the function of PbrtMT1, a tonoplast monosaccharide transporter-related gene responsible for the enhancement of fructose accumulation in pear fruit on linkage group 16, in a transient transformation experiment. This study provides genomic and genetic resources as well as potential candidate genes for fruit quality improvement in pear.Pear ( Pyrus spp.) is an important temperate fruit crop with a planting area of >1.38 million hectares and 23.9 million tons of global production in 2019 . Although pear cultivation can be traced back around 3000\u00a0years 401]).PbrtMT1. S.L.Z. provided experimental support. J.W. designed and managed the research. M.F.Q. and L.T.L. should be considered joint first authors.M.F.Q. and L.T.L. carried out data analysis, prepared the figures, and drafted the manuscript. A.K. and J.S. provided support for data analysis, interpretation of results, and manuscript writing. M.Y.S. and M.Y.Z. helped revise the manuscript. B.B., J.Y.Z., X. Zhang, S.W.L., W.L.W., and K.J.Q. helped collect samples and collected the phenotypic data. J.P.N. and J.M.L. performed the transient transformation experiments to verify the function of The datasets have been submitted to NCBI-SRA database with the BioProject ID PRJNA846875.The authors declare no conflict of interests.Horticulture Research online.supp_data_uhac141Click here for additional data file."} +{"text": "Scabolyda (Pamphiliidae) are described from the Mesozoic of northeastern China. Structures of antennae, genitalia, and legs, especially the hind tarsal claw, are preserved. The documentation of these new structures helps to link extant and fossil taxa of Pamphiliidae.Two new species and one new specimen of Scabolyda latusa sp. nov. and Scabolyda tenuis sp. nov. are described and illustrated from the late Middle Jurassic Jiulongshan Formation and the Lower Cretaceous Yixian Formation of northeastern China, respectively. A new specimen of Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014 with distinct male genitalia is documented for the first time. Based on the specimens with new and distinct structures of legs, antennae, and genitalia, the morphological characters of Scabolyda are supplemented: antenna with ca. 13\u201314 flagellomeres; fore leg with tibia without pre-apical spur; hind leg nearly 0.6 times as long as the body, hind tarsal claw without setae and its inner tooth not developed. In addition, the tarsal claw characteristics found in the new species may suggest Scabolyda has a closer relationship with Cephalciinae, rather than with Pamphiliinae.Two new species of Pamphiliidae, Mirolyda hirta Wang, Rasnitsyn and Ren, 2017, in Mirolydidae, with a unique combination of features: forewing with Sc developed, 1-Rs nearly as long as 1-M, M+Cu straight, antenna with the first flagellomere homonomous, and body surface with long and thin setae. Based on the results of the phylogenetic analysis, they suggested Mirolydidae be considered as a new family in Pamphilioidea. Pamphilioidea now comprises two extinct families, Xyelydidae and Mirolydidae, and two extant families, Pamphiliidae and Megalodontesidae.Pamphilioidea, a small superfamily with phylogenetic proximity to Xyeloidea and Tenthredinoidea, was suggested as the sister group to all remaining Hymenoptera in a recent study . OriginaTapholyda caplani Cockerell, 1933 (the Oligocene of USA and the Miocene of Russia), Acantholyda erythrocephala Linnaeus, 1758 (the Miocene of France) and possibly Acantholyda ribesalbesensis Pe\u00f1alver, and Arillo, 2002 (the Miocene of Spain) [The family Pamphiliidae consists of three subfamilies, Pamphiliinae Cameron 1890, Cephalciinae Benson 1945, and Juralydinae Rasnitsyn 1977 . Additiof Spain) ,12,13,14Atocus defessus Scudder, 1892 and Atocus cockerelli Rohwer, 1908 , Juralyda udensis Rasnitsyn, 1977 , Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014 , and Scabolyda incompleta Wang, Rasnitsyn, Shih and Ren, 2014 [So far, a total of five species in three genera are assigned to the extinct subfamily Juralydinae: f China) ,16.Ulteramus republicensis Archibald and Rasnitsyn 2015 (the early Eocene of USA), a specimen only preserved with the forewing, has not been placed in any subfamily due to the distinct character of Sc2 joining R distal to 1-Rs and limited information in the specimen [In addition, specimen .Scabolyda Wang, Rasnitsyn, Shih and Ren, 2014 [Recently, we collected four new fossil specimens of Pamphiliidae from the Jiulongshan Formation and Yixian Formation. After detailed examinations, we consider these specimens belong to a previously erected extinct genus en, 2014 . Based oThe fossil specimens were collected from the Jiulongshan Formation, Daohugou Village, Wuhua Township, Ningcheng County, Chifeng City, Inner Mongolia, China and the Yixian Formation, Huangbanjigou, Beipiao City, Liaoning Province, China. All of them described in the paper are housed at the Key Laboratory of Insect Evolution and Environmental Changes, College of Life Sciences and Academy for Multidisciplinary Studies, Capital Normal University, Beijing, China .The specimens were examined and photographed under Nikon SMZ 25 dissecting microscope with an attached Nikon DS-Ri2 digital camera system, either dry or wetted with 95% ethanol. The line drawings were prepared using Adobe Illustrator CC 2022 and Adobe Photoshop CC 2021. The wing venation nomenclature used in this study is modified from Rasnitsyn .Systematic paleontology.Order Hymenoptera Linnaeus, 1758.Suborder Symphyta Gerstaecker, 1867.Superfamily Pamphilioidea Cameron, 1890.Family Pamphiliidae Cameron, 1890.Subfamily Juralydinae Rasnitsyn, 1977.Scabolyda Wang, Rasnitsyn, Shih and Ren, 2014.Genus Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014.Type species. Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014; Scabolyda incompleta Wang, Rasnitsyn, Shih and Ren, 2014; Scabolyda latusa sp. nov. and Scabolyda tenuis sp. nov.Species included. \u00a0Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014.urn:lsid:zoobank.org:act:21407ED8-78B8-44F8-AFEE-B46DC1B887D0New specimen. CNU-HYM-NN2022101p/c (part and counterpart).Locality and horizon. Jiulongshan Formation; Daohugou Village, Shantou Township, Ningcheng County, Inner Mongolia, China ; latest Middle Jurassic of late Callovian age.Description . Male. HThorax width equal to head width, pronotum trapezoid. Mesothorax with mesoprescutum nearly as large as mesoscutellum. Cenchrus clear and distinct, metascutellum oblong. All three pairs of legs covered with short setae. Fore leg with femur slightly wider than tibia, tibia lacking the pre-apical spur and 1.2\u00d7 as long as femur C. Mid leAbdomen with seven segments; male genitalia distinct, gonocoxa inverted trapeziform, gonostylus triangular, full of short setae, and nearly as long as the gonocoxa in ventral view, digitus valviform, and covered with setae, and penial valve blunt at the apex G,H.Forewing with pterostigma sclerotized. Sc bifid, Sc2 joining R proximal to 1-Rs. 1-Rs nearly half of 1-M in length, M+Cu bent. Angle of 1-M and 1-Cu nearly 116\u00b0. Length proportions of vein 1-M: Rs+M: 1-Cu: 2-M = 0.51: 0.75: 0.49: 0.45. 2r-rs twice as long as 1r-rs, 2r-m almost parallel to 2r-rs. 3-Rs sharply curved, 4-Rs short, cu-a located proximal to the middle of cell 1 mcu, 1 m-cu 0.3\u00d7 as long as 3-Cu. Cell 1 mcu ca. 1.3\u00d7 as long as wide, cell 2a 2.7\u00d7 as long as wide. Hind wing with cell r and rm vaguely visible.Measurements (in mm). Body length (excluding antenna) 12.27; head width 2.95 and length 1.79; antenna 5.37 in length; forewing length 7.94, width 3.33; fore femur length 1.55; fore tibia length 1.81; hind leg length 7.83 .Scabolyda orientalis in Juralydinae for having Sc bifid, 1-Rs nearly half length of 1-M, Rs+M not reaching twice length of 2-M, M+Cu without extra stub, cell 1 mcu 1.3\u00d7 as long as wide in forewing.Remarks. The new specimen has the common characters of Pamphiliidae: forewing with Sc developed, R sinuate and not straight before RS base, M+Cu angularly bent. Furthermore, the specimen can be assigned to the S. orientalis based on four specimens. However, the structures about legs and genitalia were not described due to the lack of preservation of corresponding parts in these four specimens. For this new specimen CNU-HYM-LB2022101p/c, the description of both structures is added. Comparing S. orientalis with the extinct groups, there are many similarities for these structures, except for the lack of inner tooth in the claw of hind leg for S. orientalis, which is different from all other extant pamphiliids. Additionally, there is no pre-apical spur on the fore tibia for S. orientalis, which is similar to that of extant taxa, with the exception of genus Acantholyda with a pre-apical spur on the fore tibia [Wang et al. made a dre tibia .\u00a0Scabolyda latusa Zhuang, Shih, Wang and Ren sp. nov.urn:lsid:zoobank.org:act:E1FE78EA-6F56-4547-93C9-09E2D906DF37Material. Holotype, CNU-HYM-NN2022102p/c ; latest Middle Jurassic of late Callovian age.latusa\u201d (latus = wide) is a Latin word, referring to the broad antenna of this species.Etymology. The specific name \u201cDiagnosis. Large body size (nearly 20 mm in length). Body surface with obvious punctations, especially on head and thorax. Antenna with the first flagellomere nearly 4\u00d7 as long as the second flagellomere; the ratio of length to width of the following flagellomere nearly two; forewing with vein 4-Rs present and short. Hind tarsal claw with inner tooth small, located submedial.Description . HolotypHead massive and flat, its width about 1.2\u00d7 length; postocellar furrow and lateral furrow visible; middle fovea and lateral fovea indistinct; frons weakly raised. Eyes medium-sized and nearly half the length of head; temple obviously raised. Antenna ca. 2.3\u00d7 as long as the width of head, and the left antenna 15-segmented; scape 3.9\u00d7 as long as pedicel, and 0.9\u00d7 as wide as apical pedicel, its length shorter than the first flagellomere; pedicel 0.2\u00d7 as long, and almost as wide as the first flagellomere; the first flagellomere 4.9\u00d7 as long as wide and ca. 3.9\u00d7 the length of the second flagellomere; the second flagellomere 1.6\u00d7 as long as wide and slightly shorter than the third flagellomere, each of the remaining flagellomeres not more than 2.3\u00d7 as long as wide and gradually thinning toward the apex.Thorax with pronotum 0.8\u00d7 as wide as head; mesothorax wider than head, with notaulices, parapsidal suture, mesoprescutum, and mesoscutellum visible. Mesoprescutum about half of mesoscutum in width, and larger than mesoscutellum. Metathorax with metapostnotum and parapsis visible, cenchrus indistinct. Leg with hind leg visible, full of setae, and its length longer than abdomen; coxa large, inverted trapeziform, not reaching half of abdomen; trochanter and trochantellus visible. Femur markedly thick and with five spurs obviously present; middle part of femur thicker than basal part but not reaching twice. Tibia thin and nearly 1.3\u00d7 as long as femur. Tarsus partly visible; claw with two teeth and the inner tooth small E.Abdomen with seven segments preserved. Ovipositor as preserved typical of Pamphilioidea: very short, with stylets widely separated basally and meeting only at the apex D.Forewing with pterostigma slender and sclerotized, and about 3.6\u00d7 as long as wide. Sc bifid; Sc2 shorter than Sc1 and entering R before 1-Rs; R bent strongly near the middle part. 1-Rs approximately 0.5\u00d7 as long as 1-M and nearly as long as 1r-rs, inclined toward wing apex; 1r-rs ca. 0.4\u00d7 as long as 2r-rs. 2r-m parallel to 2r-rs, meeting Rs slightly distal to 2r-rs. 3r-m inclined toward wing apex and meeting 5-Rs nearly at 121\u00b0; Rs+M 1.3\u00d7 as long as 1-M; 1-M meeting 1-Cu at an angle of 127\u00b0; M+Cu obviously bending and without stub around the corner. Cell 1 mcu ca. 1.3\u00d7 as long as wide, with cu-a located distad the middle of cell. 2-M and Rs+M nearly equal in length; 3-Cu at least 2.8\u00d7 as long as 1 m-cu; 2 m-cu curved near its middle. Cell 2a ca. 3.5\u00d7 as long as wide. Hind wing with Sc present, reclined and longish. 1-Rs nearly as long as 1-M. Both 1A and 2A bent, and 2A more curved than 1A.Paratype. Female. Head flat, full of punctations, and significantly raised on both sides. Mandibles well-developed and mostly occupying more than half width of the head, with a large submedial inner tooth on both sides C,D. EyesThorax with punctations. Mesothorax with mesoprescutum, mesoscutellum, and mesoscutellar appendage visible. Cenchrus slightly smaller than mesoscutellar appendage. Hind leg with coxa, trochanter and femur preserved, coxa inverted trapezoid and nearly reaching the posterior margin of the second tergite. Abdomen with eight segments, ovipositor short and incompletely preserved.Forewing nearly reaching the seventh tergite. Pterostigma long and sclerotized. Sc developed and forked; Sc2 joining R proximal to 1-Rs and the distance between them about its own length. Radial vein obviously curved at the middle part. 1-Rs short and 0.6\u00d7 as long as 1-M. Angle of 1-M and 1-Cu nearly 129\u00b0. Length proportions of vein 1-M: Rs+M: 1-Cu: 2-M = 1.06: 1.28: 1.32: 1; cu-a located distad the middle of cell 1 mcu, 1 m-cu 0.3\u00d7 as long as 3-Cu. Cell 1 mcu 1.3\u00d7 as long as wide.Measurements (in mm). Holotype. Body length (excluding antenna) 19.64; head width 4.04, length 3.41; antenna 7.65 in length; the first flagellomere 1.53 in length; forewing length 13.52, width 5.83; hind leg length 12.66 ; abdomen 9.64 in length. Paratype. Body length 20.37; head width 4.27, length 3.01; forewing at least 14.08 in length.Scabolyda tenuis Zhuang, Shih, Wang and Ren sp. nov.urn:lsid:zoobank.org:act:9823F1EC-A545-4450-A2ED-36ECCD88D511Material. Holotype, CNU-HYM-LB2022104.Locality and horizon. Yixian Formation; Huangbanjigou, Chaomidian Village, Beipiao City, Liaoning Province, China; Lower Cretaceous.tenuis\u201d meaning thin, referring to the long and slender flagellomere of this species.Etymology. The Latin name \u201cDiagnosis. Body surface without punctations. Flagellomeres, except for the first flagellomere, slender and long, more than three times as long as wide. Forewing with Sc1 and Sc2 nearly equal in length; 2r-rs and 2r-m almost in a line, 4-Rs absent.Description . HolotypHead massive and flat, nearly 1.6\u00d7 as wide as long; postocellar furrow and lateral furrow visible. Eye medium-sized and its bottom part below the postocellar furrow. Antenna partly preserved, at least ten segments; scape 0.7\u00d7 as long as the first flagellomere, nearly as wide as pedicel; pedicel trapezoidal. The first flagellomere lightly dilated, 4.5\u00d7 as long as wide, and nearly as long as the sum of next three segments; the second flagellomere 3.6\u00d7 as long as wide; other flagellomeres left (some preserved incompletely) ca. 3.5\u00d7 as long as wide.Thorax slightly wider than head; pronotum partly preserved; mesoscutum faintly visible, nearly inverted triangle. Mesoprescutum larger than mesoscutellum. The remaining part of the thorax not discernible. Abdomen with eight segments preserved; the first segment divided medially. Genitalia poorly preserved, thus sex unknown.Forewing with pterostigma long and sclerotized, ca. 3.7\u00d7 as long as wide. Sc forked and its main vein located nearly at the middle of costal area; Sc2 almost as long as Sc1, and both of them entering vein R or C before the base of 1-Rs D; 1-Rs iMeasurements (in mm). Holotype. Body length (excluding antenna) 10.32; head width 3.16 and length 1.96; antenna at least 5.28 in length; third antennal segment 1.31 in length; forewing length 8.4, width 3.33.Scabolyda orientalis above. Both new species can be further attributed to the Scabolyda based on the combination of these morphological characters: antenna with the first flagellomere nearly three times as long as the second flagellomere; forewing with pterostigma slender, Sc developed and forked, Sc2 entering R proximal to 1-Rs, 1-Rs nearly half of 1-M in length, angle between 1-M and 1-Cu over 90\u00b0, 2r-rs close to the apical pterostigma, and 3r-m inclined toward the wing apex.Remarks. The two new species are assigned to Pamphiliidae for the same reasons in the remarks for the new specimen of Scabolyda, we selected the key characters and established the relevant key to the identification of these four species of Scabolyda.With the descriptions of two new species, the Mesozoic pamphiliids are diversified and the relevant character structures are expanded, such as antennae, legs, and genitalia. In order to better distinguish the four species of \u00a0ScabolydaKey to the species of 1. Body surface with obvious punctations, especially on head and thorax; most length-width ratio of flagellomere ca. 2\u20132.5 times..................................................................................................................... 2 Body surface without punctations; most length-width ratio of flagellomere ca. 3\u20134 times................ 3 2. Forewing with 4-Rs present; antenna with the first flagellomere nearly four times as long as the Scabolyda latusa sp. nov. second flagellomere................................................................................................ Forewing with 4-Rs present; antenna with the first flagellomere nearly three times as long as the Scabolyda orientalis Wang, Rasnitsyn, Shih and Ren, 2014 second flagellomere....................................... 3. Forewing with Sc close to vein C, 4-Rs present, Rs+M nearly twice length of 2-M; antenna with the second flagellomere shorter than the third flagellomere..................................................................... Scabolyda incompleta Wang, Rasnitsyn, Shih and Ren, 2014 ........................................................................ Forewing with Sc located at the middle part of cell C, 4-Rs absent, Rs+M shorter than twice length of 2-M; antenna with the second flagellomere nearly as long as the third flagellomere........................ Scabolyda tenuis sp. nov. .................................................................................................................................. As one of the basal groups in Symphyta, Pamphiliidae have very few Mesozoic fossil record and until now, there are only three species ,14. SomeScabolyda are as follows: antenna with ca. 13\u201314 flagellomeres, fore leg with tibia lacking pre-apical spur, mid leg with tibia having at least three spurs, hind leg nearly 0.6 times as long as the body, hind tibia with five spurs, the inner tooth of hind tarsal claw not developed and the claw without setae. Herein, we suggest treating these antenna and leg characters as diagnostic characters for Scabolyda as well.The newly documented characters of antennae and legs in Scabolyda have diversified forms: the flagellomere is relatively widest in S. latusa sp. nov.; the first flagellomere is shortest in S. incompleta; length\u2013width ratio of flagellomere (except the first flagellomere) is ca. 2\u20132.5 times in the Middle Jurassic Daohugou groups in Pamphiliidae . Howeveru groups A,B and 3u groups C,D. The Scabolyda in Juralydinae, the type of claw is very similar to that of Cephalciinae. The whole claw is slightly bent on the inner side and has a small and perpendicular tooth in the species S. latusa sp. nov. Moreover, there is no such minute tooth in S. orientalis (Xyela (Family Xyelidae) [Scabolyda, as shown in specimens. The lack of setae on the claw of Scabolyda suggests that these extinct sawflies might have held less tarsal sensing efficiency when compared with the extant sawflies.The claw, usually located at the apex of the leg, plays an important role in support and sensing ,21,22. Eientalis C, which Scabolyda might have a closer relationship with Cephalciinae, rather than with Pamphiliinae. At present, the species of extant Cephalciinae live in habitats full of conifers [Scabolyda reported. Additionally, a variety of conifer fossils have also been reported in the Daohugou Biota and Yixian Biota [Scabolyda, we suggest that the Jurassic species of Scabolyda might have lived on conifers as well. Some of them might have further adapted to conifers and established strong bonds in later evolution.The characters of the claw found in these newly reported specimens suggest that conifers . Furtherconifers , which han Biota ,26,27. TDue to the limitation on the preservation of fossil material, the classification of the extinct Pamphiliidae has previously mainly been based on wing venation, such as vein Sc developed or not, the relative length of 1-Rs, the width of the pterostigma, etc. However, the extant taxa are often classified through more diverse aspects, such as the surface colors, the spurs, and spines in tibia, the number of teeth in the mandible, and so on. This information asymmetry makes it hard to compare fossil and extant taxa in some characteristics, leading to weakened inter-relationships between them.Atocus and Tapholyda. Wang et al. [Scabolyda regarding the first to third flagellomeres and the scutum in mesothorax. Obviously, these characters are far from sufficient. In this study, we added the characteristics of antennae and legs in Scabolyda: antenna with ca. 13\u201314 flagellomeres; fore leg with tibia without pre-apical spur; hind leg nearly 0.6 times as long as the body, hind tarsal claw without setae, and its inner tooth small or absent.Although the fossil record of Pamphiliidae is currently small, researchers have tried to add features other than wing venation to the diagnostic characters. Rasnitsyn added thg et al. describeScabolyda, which may be due to the sexual dimorphism. The structures of the tarsal claw are rarely preserved and, thus, have not been reported in Symphyta fossils before. The hind tarsal claw of Scabolyda lacks setae and has a small and perpendicular inner tooth or is absent, which is morphologically more similar to that of Cephalciinae.We observed some differences in antennae among different species of"} +{"text": "Theloderma from southern Yunnan, China and northern Vietnam based on morphological and molecular evidence. Thelodermahekouensesp. nov., which had been recorded as T.rhododiscus, is the sister to T.rhododiscus. The new species differs genetically from T.rhododiscus by 4.2% and 10.7% in 16S rRNA and COI genes, respectively, and it can be morphologically distinguished from T.rhododiscus by having more densely spaced white warts on the dorsal surface, red subarticular tubercles, red metacarpal tubercles, a red metatarsal tubercle, and black dorsal and ventral surfaces in preservative. Currently the new species is only known from the China\u2013Vietnam border regions of Yunnan and Ha Giang, while T.rhododiscus has a wide distributional range in China including Guangxi, Guangdong, Hunan, Fujian, Jiangxi, and presumably Guizhou and eastern Yunnan. Including the new species, there are currently 10 Theloderma species in China and seven Theloderma species in Yunnan, where more species will probably be found.We describe a new species of Theloderma Tschudi, a genus of the family Rhacophoridae, occurs in southern and eastern areas of Asia and currently contains 26 species , T.baibungense , T.bicolor (Bourret), T.gordoni Taylor, T.moloch , T.pyaukkya Dever, and T.rhododiscus (Liu & Hu) .Thelodermarhododiscus was originally described from Mt Dayao, Guangxi, China in 1962 and Jiangxi (Mts Jiulian and Sanbai) are conspecific with T.rhododiscus from the type locality based on morphological and molecular evidence, records of T.rhododiscus from other places need further confirmation from both morphological and molecular perspectives. Our earlier phylogenetic analysis of Theloderma and northern Guangxi (Huanjiang County).In this study, we compared the Guangxi Normal University (GXNU).Specimens were collected by Guohua Yu during fieldwork in Jinxiu and Longlin counties, Guangxi, China in April and June of 2020, by Jian Wang during fieldwork in Hekou County, Yunnan, China in May and September 2020 and 2021, and by Shuo Liu during field surveys in Huanjiang County, Guangxi in September 2019. Specimens were fixed and then stored in 75% ethanol. Liver tissues were preserved in 99% ethanol. All specimens were deposited at SVL, from tip of snout to vent); head length ; head width ; snout length ; internarial distance ; interorbital distance ; upper eyelid width ; eye diameter ; tympanum diameter ; forearm and hand length ; tibia length ; foot length ; length of foot and tarsus . Comparative morphological data of other Theloderma species were taken from their original descriptions or redescriptions and cytochrome oxidase subunit I (COI) genes were amplified using the primers and experimental protocols of OL843957\u2013OL843967 and OL843972\u2013OL843982 in jMODELTEST v. 2.1.10 (BPPs).Sequences were aligned using MUSCLE with the default parameters in MEGA v. 7 . Uncorre. 2.1.10 . Bayesia. 2.1.10 under th16S and COI genes were 784 bp and 561 bp, respectively. Our phylogenetic analysis strongly supported that specimens from Yunnan and Vietnam form a clade (clade A), which is the sister to the clade consisting of topotypes and other specimens from Guangxi for the common Chinese name.Theloderma by its phylogenetic position and the following morphological characters: distinct tympanum, terminal phalanx with Y-shaped distal end, intercalary cartilage between terminal and penultimate phalanges of digits, tips of digits expanded into large discs bearing circummarginal grooves, head skin not co-ossified to skull (Thelodermahekouense sp. nov. can be distinguished from T.rhododiscus and other congeners by having a combination of the following characters: 1) small body size; 2) dorsal surface coarsely rough with large ridges and tubercles; 3) dense warts on dorsal surface; 4) absence of white markings on dorsal surface; 5) iris uniformly reddish brown; 6) discs, metacarpal tubercles, metatarsal tubercles, and subarticular tubercles red; 7) webbing between fingers, vocal sac, and vomerine teeth absent.The new species was assigned to genus to skull . ThelodeSVL 25.7 mm; Table HW 8.5 mm) nearly equal to head length (HL 8.9 mm); snout slopes upward towards the tip, slightly protruding beyond lower jaw in ventral view; canthus rostralis distinct; loreal region sloping; nostrils oval, lateral, nearer tip of snout; interorbital distance (IOD 3.0 mm) greater than internarial distance (IND 2.4 mm) and upper eyelid width (UEW 2.6 mm); pineal spot absent; pupil oval, horizontal; tympanum distinct (TD 2.2 mm), rounded, greater than half eye diameter (ED 3.1 mm); supratympanic fold indistinct; vomerine teeth absent; choanae oval; tongue cordiform, wide deeply notched posteriorly; no vocal sac.Adult male GXNU YU000398 and YU000413 have only one large black spot on dorsum whereas other types have two or more, and 3) GXNU YU000397 has two large black spots between eyes whereas other types have only one.The new species is sexually dimorphic in that the female has no nuptial pad. Black spots on dorsal surface varied among individuals in that 1) In addition to the type locality, Hekou, Yunnan, China, the new species also occurs in Ha Giang, northern Vietnam because Theloderma based on SVL, including small (28\u201335 mm), medium-sized (40\u201345 mm), and large (48\u201375 mm). Here the new species (adult SVL 25.7\u201327.2 mm) is referred to the small group, and therefore can be easily distinguished from members of the other two groups including: T.bicolor, T.corticale , T.gordoni , T.horridum , T.leporosum , T.moloch , T.nagalandense , T.phrynoderma (SVL 41.4\u201344.6 mm), and T.ryabovi .Theloderma species is summarized in Table T.rhododiscus, with which it was previously confused, by the denser white warts on dorsal surface (vs relatively sparse), red subarticular tubercles (vs white), red metacarpal tubercles (vs white), a red metatarsal tubercle (vs white), and dorsal and ventral surfaces blackish in preservative (vs tea-brown) Fig. .Thelodermahekouense sp. nov. is distinguishable from T.annae, T.auratum, T.laeve, T.lacustrinum, T.lateriticum, T.licin, T.nebulosm, T.palliatum, T.petilum, and T.truongsonense by having the dorsal surface coarsely roughened with large ridges and tubercles , and from T.albopunctatum, T.asperum, T.baibungense, T.pyaukkya, T.stellatum, and T.vietnamense by absence of white markings on the dorsal surface (vs present).T.annae, T.auratum, T.lacustrinum, T.laeve, T.nebulosm, T.palliatum, T.petilum, T.stellatum, T.truongsonense, and T.vietnamense by the uniformly reddish-brown iris (vs lacking red colouration or bicoloured); from T.albopunctatum, T.licin, T.stellatum, and T.vietnamense by lacking webbing between the fingers (vs present); from T.albopunctatum, T.asperum, T.baibungense, T.licin, T.pyaukkya, and T.vietnamense by lacking a vocal sac (vs present); from T.petilum by lacking vomerine teeth (vs present); from T.annae, T.albopunctatum, T.asperum, T.auratum, T.baibungense, T.lacustrinum, T.lateriticum, T.laeve, T.licin, T.nebulosum, T.palliatum, T.petilum, T.pyaukkya, T.stellatum, T.truongsonense, and T.vietnamense by having both dorsal and ventral surfaces of the discs reddish brown ; and from all small-bodied congeners in having red metacarpal, metatarsal, and subarticular tubercles (vs lacking red colouration).The new species further differs from Thelodermarhododiscus was thought to have a broad distribution ranging from eastern China to southwestern China and northern Vietnam (T.rhododiscus from the western part of its distribution (Yunnan and Vietnam) has never been doubted in previous publications. In this study, our molecular data and morphological comparison supports that the taxon known as T.rhododiscus from Yunnan, China and adjacent northern Vietnam should be considered representing a sibling species of T.rhododiscus, from which the new species differs morphologically by denser white warts on the dorsal surface and red subarticular, metacarpal, and metatarsal tubercles, and genetically by 4.2% and 10.7% divergence in 16S rRNA and COI genes, respectively. Vietnam . Althoug Vietnam , the taxT.rhododiscus, the range of T.rhododiscus should be revised to include Guangxi, Guangdong, Hunan, Fujian, and Jiangxi. In Guangxi, T.rhododiscus was previously known from three areas including Jinxiu , Longsheng , and Nanning . In thisT.hekouense sp. nov., there are now 10 Theloderma species in China and seven of them are distributed in Yunnan including T.albopunctatum, T.baibungense, T.bicolor, T.gordoni, T.moloch, T.pyaukkya, and T.hekouense sp. nov. Most of these species were recorded from there recently .Yunnan is the region richest in species of bug-eyed frogs in China. With the addition of ly e.g., , indicatrs e.g., reflects"} +{"text": "Embolic events play an important role in clinical everyday practice. Malignant arterial embolism is a rare nevertheless often fatal entity for cardiac, cerebral or systemic ischemia, requiring immediate diagnosis and treatment.This is a case report of a 65\u2009years\u2010old female, suffering from pulmonal adenocarcinoma, who was hospitalized due to neurological deficits caused by an acute ischemic stroke, followed by anterior myocardial infarction within 3\u2009days. Diagnostic work\u2010up revealed metastasis of the pulmonal adenocarcinoma in the right atrium and a patent foramen ovale. Histopathological examination of the coronary embolus verified paradoxical arterial embolism of the pulmonal adenocarcinoma into a coronary vessel and consequently cerebral arteries.The present case underlines the need for (i), consideration of malignant embolism, (ii) histopathological examination of the embolus to determine its etiology, and (iii) interdisciplinary discussion of individual therapeutic and prevention strategies in cancer patients with cerebral, cardiac or systemic embolic events. Besides thromboembolic causes of systemic ischemic diseases, rare entities like malignant arterial embolism may be underestimated. These diagnostic errors often result in improper treatment with oral anticoagulants, ignoring the malignant nature of the embolus, demanding surgical or interventional embolectomy,2A 65\u2009years\u2010old female was admitted to neurological emergency unit with acute onset of aphasia and brachiofacial hemiparesis of the right side . Cerebral magnetic resonance imaging (MRI) displayed an acute Middle cerebral artery (MCA) infarction (left side), Figure\u00a0. Pulsed Histological examination of the LAD\u2010embolus revealed coagulated poorly differentiated adenocarcinoma. Immunohistochemical analysis yielded a TTF\u20101 negative, CK7 positive and PD\u2010L1 positive (TP\u2010Score of 90%) tumor cell staining result, corresponding to the primary TTF\u20101 negative pulmonary adenocarcinoma with typical lepidic growth pattern . During chemotherapeutical treatment and checkpoint inhibition with Nivolumab, a dedifferentiation and upregulation of PD\u2010L1 presumably took place. A complementary transesophageal echocardiography discovered a large patent foramen ovale (PFO) and a tumor mass floating in the right atrium with two tumor plugs inserting in the fossa ovalis interdisciplinary discussion, (ii) consideration of malignant embolism, (iii) histopathological examination of the embolus to determine its etiology, and (iv) individual therapeutic and prevention strategy, based on all available information in cancer patients with cerebral or systemic embolic events.R.B. has received Honoria for Lectures and advisory boards from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer\u2010Ingelheim, Illumina, Lilly, Merck\u2010Serono, MSD, Novartis, Qiagen, Pfizer, Roche, Targos Mol Path. R.B. is a co\u2010founder and CSO for Targos Mol Path, Kassel (Germany). All other authors have nothing to disclose.Conceptualization, B.J.W., H.\u2010P.H., A.J.H., R.B.; Methodology, B.J.W., H.\u2010P.H., A.J.H., M.G.; Investigation, B.J.W., H.\u2010P.H., R.B.; Formal Analysis, B.J.W.; Resources, B.J.W.; Writing\u2014Original Draft, B.J.W., H.\u2010P.H., R.B.; Writing\u2014Review & Editing, B.J.W., H.\u2010P.H., A.J.H., L.K.H., M.G., N.M., R.B.; Visualization, B.J.W., A.J.H., L.K.H., N.M.; Supervision, B.J.W., H.\u2010P.H., L.K.H.; Data Curation, B.J.W., H.\u2010P.H., L.K.H., M.G., N.M., R.B.; Project Administration, B.J.W., R.B.; Validation, H.\u2010P.H., L.K.H., M.G., N.M., R.B.All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Informed consent was obtained from the spouse, as the legal representative of the patient of this case report, to publish the patient data, including potentially identifying individual information in this study."} +{"text": "Plagioloba derakii) together with two new combinations (P. persica and P. clavata) are established within Brassicaceae based on a decisive consideration of molecular phylogenetic dataset, morphological characters, fruit septum nature, as well as seed microsculpturing features. Results distinctly justified Arabis ottonis-schulzii as a synonym of Conringia persica and further molecular analyses proved its placement as a member of genus Plagioloba. It is also placed in a new tribe Plagiolobeae as close relatives of Conringieae and Coluteocarpeae. Finally, the diagnostic morphological characters separating the new tribe from the previously assigned tribe (Conringieae) are also discussed.One new tribe (Plagiolobeae), one new species ( Arabis L.) might demonstrate different independent lineages with artificial boundaries . The representative of Arabideae and Conringieae were also selected due to the placement of Arabis and Conringia within these tribes, respectively. Aethionema was also used as the outgroup. Indeed, the first author (ARKH) critically examined the type specimen, considerable herbarium samples of Arabis ottonis-schulzii in valid virtual herbaria , Iranian Herbaria like Herbarium of Shiraz University (HSHU), the Research Institute of Forests and Rangelands (TARI), as well as fresh plants in field studies.Aethionema erinaceum Thell., A.carneum B. Fedtsch, Anastatica hierocontica L., Conringia orientalis (L.) Dumort, Conringia clavata (DC.) Link, Arabisottonis-schulzii, Dielsiocharis kotschyi O.E. Schulz, Alyssopsis mollis (Jacq) O.E. Schulz, Alyssum desertorum Stapf., Farsetia heliophila Bunge ex Coss., Spirorhynchus sabulosus Kar. & Kir., Goldbachia laevigata (M. Bieb.) DC., Graellsia saxifragifolia (DC.) Boiss, Didymophysa aucheri Boiss., Brassica deflexa Boiss., Sisymbrium leucocladum (Boiss.) D.A. German & Al-Shehbaz, Isatisbrevipes (Bunge) Jafari and Iljinskaeaplanisiliqua), if not they are obtained from online repositories such as NCBI (https://www.ncbi.nlm.nih.gov/). Moreover, we have been used different specimens of Conringia persica (three) and Arabis ottonis-schulzii (five) to clarify their taxonomic position accurately. The validity of the sequences was checked carefully using The Basic Local Alignment Search Tool (BLAST) in NCBI. The studied species have already been listed in Online Resource 1. Moreover, tribal assignments were followed from Brassibase: https://brassibase.cos.uni-heidelberg.de/?action= phylo/ [It has been tried to obtain nrDNA sequence of studied specimens from herbarium or fresh plant materials in Shiraz University lab [50] in jModelTest2 on XSEDE v. 2.1.6 in the CIPRES Science Gateway v.3.3 . Li. LiCLADECLADEII, within tConringia species (C. clavata and C. persica) unraveled. In this case, the number of species within a monogeneric tribe Conringieae reduced into three (Conringia austriaca (Jacq.) Sweet, C. orientalis and C. grandiflora Boiss. & Heldr.). Moreover, the true position of two . Two types of seed surface ornamentations were determined at low magnification (\u00d750): Reticulate in Arabis ottonis-schulzii (C. persica variant I), Conringia clavata,C. persica (C. persica variant II) and Plagioloba crenulata, and ocellate in C. orientalis and Iljinskaea planisiliqua. However, at higher magnifications , these could be further divided into three patterns: 1) reticulate with ocellate structure in A. ottonis-schultzii (C. persica variant I), C. clavata, C. persica (C. persica variant II) and P. crenulata; 2) domate with central structure in C. orientalis; 3) domate without central structure in I. planisiliqua. The epidermal cells are larger in C. orientalis and I. planisiliqua than other species. In A. ottonis-schultzi (C. persica variant I), C. clavata, C. persica (C. persica variant II) and P. crenulata the epidermis cells are smaller, forming a pusticulate-foveate pattern with marked slime body rings and a central crater. Although C. orientalis and I. planisiliqua show the ocellate type of seed coat ornamentation, they differ in the nature of the cells. In C. orientalis seed coat cells are characterized by domate with central structure, while I. planisiliqua have flat periclinal cell walls. Seed micromorphological graphs providedA. ottonis-schultzi (C. persica variant I) with the raised-channeled anticlinal cell wall, other taxa have channeled anticlinal wall structure with different depth and width. , C. clavata, C. persica (C. persica variant II) and P. crenulata, while it is clearly convex in C. orientalis and flat in I. planisiliqua.The anticlinal cell wall boundaries show variation between genera and species. Except in d width. . AnticliC. orientalis and I. planisiliqua, the epidermal cells are perpendicular to the long axis of the fruit, while in A. ottonis-schulzii (C. persica variant I), C. clavata, C. persica (C. persica variant II) and P. crenulata are parallel. Epidermal cell shapes in the septum can be categorized into four groups: The first group is mainly comprising very long oblong cells with blunt or tapering end walls and striate anticlinal thin wall , C. persica (C. persica type II) and P. crenulata with very long oblong cells, blunt end walls and undulated anticlinal thick wall. Phenotypic variation within septa of studied taxa, and their close relatives were studied for the first time and clearly identified four types : In the ientalis ; The thiick wall . FinallyA. ottonis-schulzii, a morphologically enigmatic species in the genus Arabis plus Conringieae. Our molecular study clearly shows that A. ottonis-schulzii is not nested within Arabideae, and clarified its phylogenetic position within paraphyletic Conringieae. Furthermore, the studied taxon demonstrated its close phylogenetic relationship with Plagioloba. As recently discussed, the first author (ARKH) morphologically recognized two variants of C. persica. The first is totally similar to the type of C. persica collected by Kotschy in 1842 (339!), but the second variant of C. persica is considered to be new due to molecular data Al-Shehbaz, Fourraea Greuter & Burdet, Pseudoturritis Al-Shehbaz, Rhammatophyllum O.E. Schulz, Streptanthus Nuttall within about five tribes [e.g., Arabis delimitation [Arabis s. str. species and A. ottonis-schulzii (C. persica variant I) reveals that there are a number of morphological characters that readily distinguish the Arabis species from A. ottonis-schulzii (C. persica variant I). Based on the current study, A. ottonis schulzii (C. persica variant I) is a glaucous glabrous plant that almost characterized by falcate long delicate fruits, small dark green or greenish-violet perfoliate leaves, yellow or pale yellow petals and incumbent cotyledons. Generally, the original description of A. ottonis-schulzii (C. persica variant I) include several inaccuracies; for instance, the petals described as white in color in Flora Iranica [Arabis specimens. Moreover, A. ottonis-schulzii (C. persica variant I) differs from the remaining Arabis species by presence of slightly saccate sepals and falcate fruits. The interspecific taxonomic delimitation of A. ottonis-schulzii has some confusions too; e.g., A. ottonis-schulzii (C. persica variant I) and C. persica (C. persica variant II) are glabrous and glaucous with almost fleshy perfoliate stem leaves [A.ottonis-schulzii (C. persica variant I) is almost similar in all aspects of leaves and flowers to Conringia persica (variant II) and foreign herbaria as both Conringia persica variants with different characters described as C. persica in Flora of Iran [The number of es e.g., . Accordimitation . A criti Iranica , while tm leaves . As a reiant II) . Two men of Iran . Arabis ottonis-schulzii (C. persica variant I) is mainly distributed in the south, central Iranian plateau and Afghanistan, while C. persica (C. persica variant II) is growth in west of Elburz, western slope of Zagros, N of Turkey, the Caucasus along with north of Iraq. With respect to their geographical distribution, their ecological environments are critically differing from each other as A. ottonis-schulzii (C. persica variant I) resistant more to dry environmental conditions (xerophytic) than C. persica (mesophytic) (C. persica variant II). Geographically, the two mentioned species are distinct. Conringia was nested within tribe Brassiceae by numerous authorities (see introduction). Based on what Al-Shehbaz mentioned in his paper [Conringia persica comprises the shortest flowers among Conringia species with non-saccate sepals, and this study is completely in agreement with the former but not with the latter idea. To our knowledge, he described C. persica , while we found slightly saccate sepals in both variants of C. persica. Regarding C. persica (variant I), Anderson and Warwick exclude Conringia from their study and support the monophyly of Brassiceae [Conringia with Brassiceae [Conringia within this tribe [C. clavata and Noccaea Moench as closely related species, and proved the strong affinity of Conringia to the tribe Coluteocarpeae, as showed in previous papers [ndhF, PHYA, as well as combined dataset with high and low levels of Bayesian and bootstrap supports, respectively [C. persica and C. clavata. Their well-established molecular analyses were also suggested the inclusion of C. persica and C. clavata to the tribe Coluteocarpeae. However, the present study confirmed the evolutionary affinity of tribes Noccaeeae and paraphyletic Conringieae (Expanded lineage II). Generally, Beilstein et al. also suggested that it is possible to transfer C. persica, C. clavata and maybe other members of Conringia to Noccaeeae [P. crenulata varieties and A. ottonis-schulzii (C. persica variant I) specimens in their study. The present study undoubtedly distinguishes Plagioloba as a monophyletic taxon in their study and assumed that they resolved delimitation of Arabis by introducing three different genera [trnL-F failed to support the monophyly of Coluteocarpeae and C. orientalis (Conringieae) [Conringia) as monophyletic. Nikolov et al. highlighted the close relationship of Noccaea vesicaria (L.) Al-Shehbaz, Arabis ottonis-schulzii and Conringia orientalis, but their data were not sufficient to explore the tribal assignment and taxonomic circumscription of Arabis ottonis-schulzii [German et al. and our study clarified the close relationship between onringia . It alsole fruit . Koch ant genera . Accordiingieae) . They clschulzii , as we dPlagioloba, Warwick et al. were molecularly studied Malcolmia complex and noticed the distinct taxonomic position of Plagioloba [Plagioloba to a specific tribe. Later studies highlighted the close affinity of Plagioloba and Conringia and strongly supported the placement of Plagioloba within Conringieae [Malcolmia and Plagioloba (presence of auriculate to sagittate stem leaves and absence of furcate trichomes are in Plagioloba) [Regarding agioloba . Neverthringieae , 68. Al-gioloba) .Micromorphological studies: It is believed that seed microsculpturing is a significant character to identify species [e.g., es e.g., -72. Seedes e.g., , 22, 33,es e.g., , as welles e.g., . Malcolmia, Plagioloba and Strigosella Boiss. based on seed micromorphology [The relevance of seed coat characters was not supported in the delimitation of genera in the study of Moazzeni et al. , while Krphology -77. Theirphology . They surphology , and ourMalcolmia complex [Ionopsidium Rchb. [Friedrichkarlmeyeria umbellata (F.K. Mey.) Tahir Ali & Thines, Ihsanalshehbazia granatensis (Boiss. & Reut.) Tahir Ali & Thines) [Friedrichkarlmeyeria umbellata, while Ihsanalshehbazia granatensis has different septum nature. However, none of above mentioned papers did not prepare highly transparent septum cells and only superficially studied fruit septa. In contrast with modern molecular workers who almost trust the molecular dataset, we broke from tradition when we tried our best to examine septum cells in his field trips during ten years, he found out that A. ottonis-schulzii (C. persica variant I) and C. persica (variant II) are the same species. Our detailed morphological studies together with molecular data, confirmed this statement as previously did by Assadi et al. [C. persica variant I) with C. persica (variant II), which are collected from Iran, Turkey and Iraq. They are morphologically differing from each other . The type specimens which were collected by Kotschy was A. ottonis-schulzii, which already synonymized under C. persica (variant I). Thus, the current study supports the removal of Arabis ottonis-schulzii (C. persica variant I) as a member of Arabideae and justified Plagioloba persica (Boiss.) A.R. Khosravi & A. Eslami-Farouji, comb. nov. as a new combination. Moreover, we propose the new combination of Plagioloba clavata ((DC.) Link) A.R. Khosravi & A. Eslami-Farouji comb. nov,. A new species, Plagioloba derakii A.R. Khosravi & A. Eslami-Farouji sp. nov. (C. persica variant II), is also described due to molecular, morphological and micromorphological results , and seed and septum micromorphological data critically supports our idea of periclinal cell walls and the parallel (vs. perpendicular) epidermal cells direction to the long axis of the fruit septum in Plagiolobeae. Moreover, the size of periclinal cells in seed coat is smaller (vs. larger) in tribe Plagiolobeae (see beae see -4.Plagioloba (5 spp.) as follows:The tribe includes Plagioloba derakii A.R. Khosravi & A. Eslami-Farouji sp. nov. \u2014HOLOTYPE:\u2014Persia, Fars Province, NW of Shiraz, Kuh-e Barfi (Kuh-e Derak), 2674 m, (29\u00b040'59.9\"E-52\u00b024'07.3\"N), 2009.03.31, A.R. khosravi 42048 (HSHU). Etymology:\u2014The epithet \u2018derakii\u2019 refers to the type species location, Derak Mountain.Description:\u2014Plant annual. Stems ascending to erect, 5-20 cm long, simple or branched from base, often violet stemmed. Basal leaves entire, cuneate, cauline leaves deeply cordate, amplexicaul, pedicels 2-4 mm. Sepals oblong, ascending, the inner pair slightly saccate, 3\u20134.5 \u00d7 0.5\u20131 mm; petals yellow, 3.5-4 mm long, obcuneate. Fruiting pedicels 0.4-1.2 cm., ascending, thickened. Siliqua erect-spreading or loosely appressed to stem, 20-50 \u00d7 1-1\u00b75 mm, linear, subterete, with a very short punctiform stigma; nerves several, indistinct. Seeds pale brown, oblong, 1.2 mm long, 0.5 mm broad with reticulate sculpture. , larger flowers up to 5 mm , fruits mostly erect up to 5 cm (vs. fruit mostly curved up to 7 cm).Phenology:\u2014April-June (flowering period), June-July (fruiting time).Distribution area:\u2014W Iran, E Turkey and N Iraq & Caucasus.Additional specimens examined:\u2014Iran: Kurdistan, 16 km N of Husainabad between Sanandaj and Saqez, exposed hill of upland plateau, 2160 m, 21 May 1996, J.C. Archibald 2114 (RBGE!). \u2013Iran: Azerbaijan, frontier of Turkey beyond Qotur, 2000-2100 m, 10 June 1971, Coll. Jennifer Lamond 3946 (RBGE!) \u2013 Turkey: B9 Agri, 2 km SW of Hamur , Colonising earthy banks in steppe. 1670 m, 02 June 1966, Davis 44034 (RBGE!). \u2013Turkey: Prov. Kars, Fallow field on plain, 1800 m, 15 Jun 1957 (RBGE!). Iran: Fars, 58 km W of Shiraz, 3600 m, 16 May 1964, Martin L. Grant 15542 (HSHU!); Iran: Azerbayjan, road of Oshnaviyeh to Urmia, 08 Jun 2009, A.R. Khosravi & Assadollahi (HSHU!) Proposed conservation status:\u2014According to IUCN Red List category [P. derakii.category , an invu Plagioloba persica (Boiss.) A.R. Khosravi & A. Eslami-Farouji comb. nov. Basionym: Conringia persica Boiss., Diagn. Pl. Or. Nov. Ser. 1, 6: 12 (1845). Type: \u2014IRAN. Prov. Fars: Shiraz, Kuh-e Barfi, KY. 339! 1842.05.04, T. Kotschy, 339 (holotype K!). Syn.: Arabis ottonis-schulzii Bornm. & Gauba, Feddes Repert. 39: 80. Tab. 198a (1935). \u20146: 12 184. Type: \u2014Distribution: \u2014South, central Iranian plateau and Afghanistan.Plagioloba clavata (Boiss.) A.R. Khosravi & A. Eslami-Farouji comb. nov.\u2014Conringia perfoliata (C.A.Mey.) N.Busch, Komarov, Fl. URSS 8: 497 (1939). Type: \u2014IRAN. Prov. Gilan, Talish prope Swant, C.A. Mey., (holotype LE!). Syn.: Sisymbrium perfoliatum C.A. Mey., Verz. Pfl. Cauc. 188 (1831); Conringia clavata Boiss., in Ann. Sci. Nat. 17: 84 (1842). Distribution:\u2014Syria, Lebanon, Turkey, Caucasus, Iran, Afghanistan, C. Asia (Turkmenia).Plagioloba crenulata (DC.) D.A. German Plagioloba meyeri (Boiss.) D.A. German Authors have a financial relationship with the organization that sponsored the research."} +{"text": "Scientific Reports 10.1038/s41598-022-21513-9, published online 17 November 2022Correction to: Sanne Grundvald Boelt was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cA.A. contributed to the conception and idea of the work. N.M.N., A.S.C., L.B. and A.A. contributed to the design of the study. N.M.N., A.S.C., L.B. S.G.B contributed to the acquisition of data. N.M.N., A.H., L.B., S.G.B and T.G.J. contributed to the analyses of the data. All authors contributed to the interpretation of the data and the results in the manuscript. N.M.N. drafted the manuscript, made Fig.\u00a01, T.G.J. made Fig.\u00a02. All the authors revised the manuscript critically and has approved the final version.\u201dThe original Article has been corrected."} +{"text": "B\u2013N/B\u2013H transborylation mechanism.The reduction of nitriles to primary amines is a useful transformation in organic synthesis, however, it often relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48\u201395%) and chemoselectivity were observed. DFT calculations and mechanistic studies support the proposal of a double Primary amines are prevalent throughout organic synthesis, finding regular application in materials chemistry, pharmaceuticals, and agrochemicals 1\u20133]. T\u20133. T1\u20133]3 is the only known boron-based catalyst for nitrile hydroboration [3]\u2212, this method displayed good reactivity but limited chemoselectivity. Like [HBEt3]\u2212, boranes are stoichiometric reducing agents, but are considered to be milder than [HBEt3]\u2212 \u201342 was uH3B\u00b7SMe2 and the rylation . Route AN adduct , suggest3B\u00b7SMe2 into a catalyst. B-N/B\u2013H transborylation is proposed to serve as the key turnover step in catalysis, supported by computational mechanistic studies. This approach uses both a commercially-available catalyst and turnover reagent, providing good user accessibility, and displays comparable chemoselectivity to current state-of-the-art catalysed hydroboration methods [In summary, a borane-catalysed hydroboration of nitriles to give primary amines has been developed, transforming the previously stoichiometric reagent H methods .F. M., A. C. W. K., F. G., A. J. H., K. N., and A. D. B. completed all practical laboratory work. D. R. W. completed all computational analysis. A. D. B., K. N., D. R. W., and S. P. T. conceived the reactions and wrote the manuscript. S. P. T., T. A. H., and T. L. advised investigations.File 1Experimental details, characterisation data, and copies of NMR spectra."} +{"text": "Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. The gene-regulatory mechanisms underpinning endothelial specialization are largely unknown, as are the roles of chromatin organization in regulating endothelial cell transcription. To investigate the relationships between chromatin organization and gene expression, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-sequencing assays at specific time points. Long-range intrachromosomal contacts increase over the course of differentiation, accompanied by widespread heteroeuchromatic compartment transitions that are tightly associated with transcription. Dynamic topologically associating domain boundaries strengthen and converge on an endothelial cell state, and function to regulate gene expression. Chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes essential to vascular biology. Chromatin dynamics guide transcription in endothelial cell development and promote the divergence of endothelial cells from cardiomyocytes. \u2022In endothelial differentiation, compartment transitions regulate gene expression\u2022New TAD boundaries and chromatin loop anchors coordinate endothelial activation\u2022Frequent, growing chromatin loops accompany essential endothelial gene expression\u2022Cardiomyocytes evidence a markedly different topology versus endothelial cells cis contacts increase in endothelial cell differentiation, as do hetero-euchromatic compartment transitions, which are tightly associated with transcription. Specification occurs alongside new TAD boundaries and chromatin loop anchors, features that distinguish endothelial cells from cardiomyocytes, which evidence a dissimilar topology. Multiple forms of chromatin organization guide transcription in differentiation, driving endothelial divergence from cardiomyocytes.Alavattam, Mitzelfelt, and colleagues reveal that long-range Endothelial cells, a mesoderm-derived cell population, line the entirety of the circulatory system. Their functions are complex and critical, including angiogenesis, blood clotting, barrier function, vasomotor function, and fluid/nutrient filtration. Endothelial cell dysfunction is a prominent feature of many pathological conditions, including nearly all cardiovascular diseases . Complexin situ DNase Hi-C that spread outward with differentiation, increasing the numbers of \u201cfar\u201d cis interactions. Next, we examined the cis chromatin contact probability P(s) for pairs of genomic loci stratified by distance s for cis interactions . TADs comprise local \u201cneighborhoods\u201d of increased chromatin contact frequency and are often delimited by insulator sequences . Becausecis chromatin interactions are increasingly restricted within TAD boundaries proximal to (within\u00a0\u00b180 kb of) boundaries lost in differentiation (hPSC-specific boundaries), boundaries gained in differentiation (EC-specific), and shared boundaries (common to hPSC and EC). We found that DEGs are depleted from lost and gained boundaries and enriched at shared boundaries D. RelatiTo investigate this, we examined the interplay of TADs and compartments. TADs in A compartments are smaller than those in B compartments G, a likeThis led us to explore how TAD-compartment interrelationships influence gene expression. We examined the enrichment of up- and downregulated DEGs at TAD boundaries grouped by stable and dynamic compartments F. RegardOur analyses also revealed that shared TAD boundaries in stable A regions of the genome are slightly but significantly enriched in both up- and downregulated DEGs F, gray. CD31 in transcriptional regulation and suggests the existence of PPIs that function in specific aspects of development . These iSince PPI dynamics occur amid changes in genomic compartmentalization and S3, MECOM, which encodes a transcription factor that promotes arterial EC identity contacts for a single chromosome, chromosome 3 .Further information and requests should be directed to and will be fulfilled by co-lead contact Charles E. Murry or various software packages . StrategK.G.A., K.A.M., W.S.N., and C.E.M. wrote the manuscript with edits provided by all other authors. K.G.A., K.A.M., G.B., W.S.N., and C.E.M. designed the experiments. K.A.M. conducted wet-lab experiments; K.G.A., G.B., P.A.F., and X.Y. conducted dry-lab experiments. K.G.A., K.A.M., X.Y., L.P., A.B., N.J.P., H.S.C., W.S.N., and C.E.M. interpreted the results. W.S.N. and C.E.M. obtained resources and were the overall supervisors of this work."} +{"text": "Drosophila,\u201d by Amina Dulac, Abdul-Raouf Issa, Jun Sun, Giorgio Matassi, C\u00e9lia Jonas, Baya Ch\u00e9rif-Zahar, Daniel Cattaert, and Serge Birman, which published online on October 7, 2021, an author was inadvertently omitted from the author line. Zohra Rahmani should appear sixth and be credited with performing research and analyzing data. The article has been updated online, and the corrected author line, affiliations, and contribution statement are included below.In the article \u201cA Novel Neuron-Specific Regulator of the V-ATPase in Author contributions: A.D., D.C., and S.B. designed research; A.D., A.-R.I., J.S., G.M., C.J., Z.R., B.C.-Z., D.C., and S.B. performed research and analyzed data; A.D. and S.B. wrote the paper with input from all authors."} +{"text": "Dear Editor,Sepsis, defined as life\u2010threatening organ failure induced by a dysregulated host response to infection, is a serious public health problem globally.In this study, the patients from 53 hospitals in six regions of China, who developed sepsis or newly admitted patients that met the diagnostic criteria of sepsisA total of 10,307 children in the PICU were observed during the study period, among which 580 children met the inclusion criteria Table . The oveMore than one\u2010third (37.8%) of these individuals had at least one underlying comorbidity, with the respiratory (24.5%) and hematological (11.6%) systems being the most often afflicted Figure\u00a0. In termStaphylococcus aureus (8.6%) was the most isolated bacteria, followed by Klebsiella species (6.3%), Streptococcus pneumonia (6.3%), and Escherichia coli (5.7%). The rate of fungi, viruses, and parasites isolated was of 8.1, 20.9, and 0.3%, respectively , followed by the abdominal cavity (13.8%) Figure\u00a0. Total o Figures\u00a0 and F. Mn\u00a0=\u00a0197, 34.9%), followed by acute gastrointestinal injury and sepsis\u2010associated encephalopathy Table .This extensive, nationwide, multicenter cross\u2010sectional study of 10,307 children in 53 hospitals reveals that pediatric sepsis is still quite common in China, with a PICU sepsis prevalence of 5.6% and high septic shock mortality (18.3%). Although our reported prevalence was lower than the estimated incidence of childhood sepsis in Asia (15.3%),To sum up, till now, deficiencies remain in the diagnosis and treatment of sepsis in China. Sepsis remains high prevalence and mortality. Evidence using epidemiological data will improve the understanding and management of sepsis and the application of relevant septic guidelines in the future, which are essential for improving the prognosis of pediatric sepsis.B. T. N., Y. W., C. F. L., and S. Y. Q. designed the study. All the participant hospitals contributed to the collection of data. S. W., F. Y., and Y. Y. Z. analyzed the data. S. W., Y. Y. Z., F. Y., and B. T. N. wrote the manuscript. B. T. N., S. W., F. Y., Y. Y. Z., K. A., and Y. W. discussed and interpreted the results. Y.L.X., X. L. L., Y. M. Z., W. G. M., Y. P. J., D. W., Y. M. L., Y. Y. Y., Y. H., T. L. L., G. P. L., F. X., S. Y. Q., C. F. L., and Y. W. were the representatives of the top 13 hospitals in terms of number of the collected cases. All the name of participant hospitals were listed in The authors declare no conflicts of interest to report.This work was supported by the National Key Research and Development Program of China , the Shanghai Municipal Commission of Health and Family Planning (2016ZB0104), the Shanghai Natural Science Foundation of China (19ZR1432900) and the Shanghai Translational Medicine Collaborative Innovation Center (TM202012).This study was approved by the ethical committee of Shanghai Children's Medical Center (SCMCIRB\u2010K2018030).Supporting InformationClick here for additional data file."} +{"text": "In this article one of the following author last name Huijsmans, M.A. contains a typo.For Huijsmans, M.A. it should not be \u2018ij\u2019, but an \u2018y\u2019.The correct name is Huysmans, M.A.The original article has been updated."} +{"text": "Orientia tsutsugamushi. Species of the genus Leptotrombidium are investigated most thoroughly, particularly in SE Asia, and a few are proven vectors for the pathogen. The mentioned association, however, is not the only one among trombiculids. Here, we present a list of chiggers indicated in the literature as positive for bacterial pathogens, tested throughout almost 100 years of research. Taxonomic identities of trombiculids follow recent revisions and checklists. Results point at 100 species, from 28 genera, evidenced for association with 31 bacterial taxa. Pathogen-positive mites constitute around 3.3% of the total number of species comprising the family. Discussed arachnids inhabit six biogeographic realms and represent free-living instars as well as external and internal parasites of rodents, soricomorphs, scadents, lagomorphs, peramelemorphs, bats, passerine birds, reptiles and humans. A variety of so far detected bacteria, including novel species, along with the mites\u2019 vast geographical distribution and parasitism on differentiated hosts, indicate that revealing of more cases of Trombiculidae-pathogens association is highly probable, especially utilizing the newest techniques enabling a large-scale bacterial communities survey.Mites of the family Trombiculidae are known for playing a role in maintaining and spreading the scrub typhus etiologic agent, an intracellular Gram-negative bacterium, Trombiculidae, as understood by Kudryashova being the immunological reaction of the host\u2019s body to larval lytic secretions, and the capability of acquiring and spreading bacterial pathogens, the source of which being the vertebrate organisms [Trombiculid larvae feed basically on dissolved connective tissue similar in composition to a plasma, however, in single cases, ingestion of blood has been also reported ,13,14. Frganisms ,17,18.Leptotrombidium spp. are best recognized for maintaining and transmitting an etiologic agent of scrub typhus, intracellular bacterium, Orientia tsutsugamushi , formerly under the names of Rickettsia tsutsugamushi and R. orientalis [Leptotrombidium spp.\u2014O. tsutsugamushi is most well explored in literature. Issues raised so far concern scrupulously investigated ecological, epidemiological, molecular and geographical aspects of the chigger-borne rickettsiosis occurrence in general as well as in particular areas of China, South Korea, Japan, Russia, Taiwan, Thailand and Asia\u2013Australia\u2013Pacific region, which together constitute the so called \u2018tsutsugamushi triangle\u2019 [Among Trombiculidae, representatives of Hayashi, 20 and countries of records, reported in the published sources.Acomatacarus Ewing, 1942Genus: Acomatacarus sp.O. tsutsugamushi revealed during research in China. Infected larvae were collected from the lesser ricefield rat Rattus losea , the brown rat R. norvegicus , the black rat R. rattus , the house mouse Mus musculus , M. bactrianus kakhyenensis and the Asian house shrew Suncus murinus [Mites of this genus are known for the association with omorpha) ,43,44,45Ascoschoengastia Ewing, 1948Genus: Ascoschoengastia spp.Bartonella spp. Strong et al., 1915 , O. tsutsugamushi and Rickettsia sp. da Rocha-Lima, 1916 . In the case of the latter two, a co-infection was observed in Thailand. Tested chiggers parasitized the Asian house rat R. tanezumi Temminck, 1844, R. rattus, R. norvegicus, R. rattus-complex , the Savile\u2019s bandicoot rat Bandicota savilei Thomas, 1916, the greater bandicoot rat B. indica , the northern treeshrew Tupaia belangeri and the common treeshrew T. glis Diard and Duvaucel, 1820 . Reports come from India, Thailand and Vietnam [Undetermined to the species level representatives of the genus are known to harbor Vietnam ,48,49,50A. audyi O. tsutsugamushi. Collected in the Malayan forest [Individuals of the species were positive for the presence of n forest .A. indica Euschoengastia indica. Associated with O. tsutsugamushi and R. typhi . Positive larvae fed on rats, including the ricefield rat R. argentiveter and squirrel. Collected and tested in China, Indonesia, Malaysia, Thailand and Vietnam [Species mentioned also as Vietnam ,52,53,54Blankaartia Oudemans, 1911Genus: Blankaartia spp.Bartonella spp., B. tamiae Kosoy et al., 2008 and O. tsutsugamushi. Host animals included rats from R. rattus-complex, R. rattus, R. tanezumi, R. argentiventer, B. indica, B. savilei and the fawn-colored mouse M. cervicolor Hodgson, 1845. Records originate from Thailand and Vietnam [In chiggers from this genus, the following pathogens were detected: Vietnam ,48,50,55B. acuscutellaris O. tsutsugamushi. Infected larvae were collected from T. glis and rodents including R. rattus in Thailand [Known for association with Thailand ,52.B. sinnamaryi Rickettsia felis-like and chiggers were collected from passerine birds: the ruby-crowned tanager Tachyphonus coronatus and the pale-breasted thrush Turdus leucomelas Vieillot, 1818 (Aves: Passeriformes) in Brazil [Pathogen detected in this species was described as n Brazil ,57.Cheladonta Lipovsky, Crossley and Loomis, 1955Genus: C. costulata R. helvetica Beati et al., 1993 and R. monacensis Simser et al., 2002 and associated with the following bacteria-positive host rodents: the bank vole Myodes glareolus , the yellow-necked wood mouse Apodemus flavicollis , the common vole Microtus arvalis and the European wood mouse A. sylvaticus . Mites captured in Slovakia [Species harboring C. ikaoensis O. tsutsugamushi and collected from field rodents, mostly the large Japanese field mouse A. speciosus speciosus , the small Japanese field mouse A. argenteus argenteus , Eothenomys kageus Imaizumi, 1957 and the Japanese grass vole M. montebelli montebelli in Japan [Associated with in Japan ,60.Ericotrombidium Vercammen-Grandjean, 1965Genus: E. jayewickremei Orientia tsutsugamushi-positive larvae of this species were captured in India while feeding on R. rattus [. rattus .Euschoengastia Ewing, 1938Genus: Euschoengastia sp.O. tsutsugamushi [Individuals of the genus collected from Malayan jungle rats tested positive for ugamushi .E. koreaensis Jameson and Toshioka, 1954Orientia tsutsugamushi-positive larvae were collected from A. agrarius, the Korean red-backed vole M. regulus and the Ussuri white-toothed shrew Crocidura lasiura Dobson, 1890 in South Korea [th Korea ,62,63.Eutrombicula Ewing, 1938Genus: Eutrombicula spp.Rickettsia sp., and species very closely related to R. conorii, R. felis and R. typhi. Larvae were collected from birds in Brazil and from the hispid cotton rat Sigmodon hispidus Say and Ord , 1825 in the USA (North Carolina) [Individuals of this genus tested positive for sequences of arolina) ,64.E. alfreddugesi Rickettsia bellii-like sequence was detected in isolates obtained from larvae of the common Northamerican chigger parasitizning snake Philodryas nattererii Steindachner, 1870 (Reptilia: Squamata) in Brazil [n Brazil . R. bellii represent a non-pathogenic ancestral group within Rickettsiaceae, not the typhus or the spotted fever group. On the other hand, the species is evidenced to elicit an immune response in capybaras and horses, therefore, we included this association. Mechanisms of R. bellii possible pathogenicity, however, require more research [Remarks: According to Sajle , R. bellresearch .E. tinami Candidatus Rickettsia colombianensi. Captured parasitizing the Andean sparrow Zonotrichia capensis and T. coronatus in Brazil (Aves: Passeriformes) [Species evidenced to harbor a novel bacterium iformes) .E. wichmanni O. tsutsugamushi in Thailand [Host-questing larvae of the species, collected with black plates, were reported to test positive for Thailand .Gahrliepia Oudemans, 1912Genus: Gahrliepia sp.O. tsutsugamushi and Rickettsia sp. Collected from R. rattus-complex, R. tanezumi, B. savilei, B. indica and T. belangeri. Records come fromChina and Thailand [Known for the association with Thailand ,45,47,50G. saduski Womersley, 1952A. speciosus) larvae captured in Japan tested positive for O. tsutsugamushi [Unengorged and parasitic in Thailand [Individuals of the species contained Thailand .Helenicula Audy, 1954Genus: Helenicula sp.O. tsutsugamushi and Rickettsia sp., parasitizing R. tanezumi, B. savilei and B. indica in Thailand [Genus listed among mites positive for Thailand .H. miyagawai Euschoengastia miyagawai) captured with chigger traps and collected from rodents (mainly A. agrarius) revealed the presence of O. tsutsugamushi in South Korea and some other Rickettsia species (most probably not O. tsutsugamushi) in Japan [Species individuals Candidatus Orientia chiloensis Abarca et al. 2020, a novel bacterium causing scrub typhus in the area of subantarctic Chile. Parasitic mites were collected from human hosts while unengorged individuals from low vegetation [The species is a proven vector for getation .H. eloisae Stekolnikov and Silva-de la Fuente, 2021Orientia spp-positive chiggers fed on the olive-colored akodont Abrothrix olivacea , the Sanborn\u2019s akodont A. sanborni and the Valdivian long-clawed akodont Geoxus valdivianus in Chile [in Chile ,74,75.H. hertigi Candidatus Rickettsia colombianensi. Larvae were collected from the colilargo Oligoryzomys sp. Bangs, 1900 in Brazil [A species reported to carry a novel bacterium n Brazil .Hirsutiella Schluger and Vysotzkaja, 1970Genus: H. zachvatkini R. helvetica and R. monacensis. Fed on Rickettsia-positive rodents: M. glareolus, A. flavicollis, M. arvalis and A. sylvaticus, captured in Slovakia [Species tested positive for Slovakia .Intercutestrix Brennan and Yunker, 1966Genus: I. mondolfi Brennan and Yunker, 1969Coxiella burnetii . Larvae were attached to the nasal cavities of the Central American spiny rat Proechimys semispinosus in Panama [Species associated with n Panama .Leptotrombidium Nagayo, Miyagawa, Mitamura and Imamura, 1916Genus: Leptotrombidium spp.Leptotrombidium spp. were reported to carry B. tamiae, O. tsutsugamushi and Rickettsia sp. Infected chiggers parasitized small mammals: R. rattus, R. rattus-complex, R. argentiventer, R. tanezumi, the Polynesian rat R. exulans , M. cervicolor, B. indica, B. saliviei, the Royle\u2019s mountain vole Alticola roylei and T. belangeri as well as swarmed on the ground and plants (unfed parasites). Above observations come from India, Indonesia, Pakistan, Taiwan and Thailand [Representatives of Thailand ,68,78,79L. akamushi O. tsutsugamushi vectors. Positive larvae were obtained from Rattus spp., R. exulans, as well as from the vegetation. Records come from Japan, Malaysia, New Guinea, Philippines and Solomon Islands [Species listed among the most important Islands ,54,60,80L. arenicola Traub, 1960Orientia tsutsugamushi-infected larvae were collected from Rattus spp. and from the ground in Indonesia and Malaysia [Malaysia ,82.L. arvinum O. tsutsugamushi in Thailand [Host-seeking larvae collected from the black plates tested positive for Thailand .L. bodense O. tsutsugamushi. Malaysia [Unengorged larvae obtained with the above-mentioned technique were positive for Malaysia .L. chaigraiensis Tanskul and Linthicum 1997O. tsutsugamushi. Infected larvae were taken from the bodies of R. losea and R. rattus captured in Thailand [Species listed among proven vectors of Thailand ,85.Leptotrombidium genus by Stekolnikov [L. chiangraiensis should be considered a synonym of L. imphalum, as metric traits of both taxa overlap. Still, molecular sequences subsequently provided by Kumlert et al. [L. chaigraiensis separately.Remarks: According to revision of kolnikov and checkolnikov , L. chiat et al. indicateL. deliense L. deliensis) as a proven and widespread vector of O. tsutsugamushi, however, it is also reported for the association with Borrelia spp. Swellengrebel, 1907 , Rickettsia sp., species close to R. australis, R. felis Bouyer et al., 2001, R. conorii Brumpt, 1932, R. raoultii Mediannikov et al., 2008, R. rhipicephali Burgdorfer et al., 1978 and R. typhi, as well as a novel species Candidatus Rickettsia jingxinensis. Bacteria-positive larvae were obtained from A. agrarius, the Indian mole-rat B. bengalensis Gray, 1835, B. indica, A. roylei, R. rattus, the buff-breasted rat R. tanezumi flavipectus , R. tanezumi, the Sikkim rat R. andamanensis , R. exulans, R. norvegicus, R. losea, Rattus spp., the small white-toothed rat B. berdmorei , T. belangeri (mentioned as T. belangeri persurae), T. glis and S. murinus (mentioned as S. murinus fulvo-cinerea) as well as from the moist marshlands (host-questing larvae). The above observations were made in Australia, China, India, Indonesia, Malaysia, Myanmar, Pakistan, Papua New Guinea, Philippines, Singapore, Taiwan (including Pescadores), Thailand and Vietnam [The species is most frequently listed Echymipera kalubu cockerelli as well as questing ones taken from the ground in Papua New Guinea, Philippines and Malaysia tested positive for O. tsutsugamushi [Parasitic larvae feeding on the common echymipera ugamushi ,83,104.L. fujii O. tsutsugamushi. Infected larvae parasitized A. speciosus and unengorged chiggers were collected from ground and vegetation in Japan [Species mentioned as positive for in Japan ,70. L. gaohuense Wei, Tong and Shi, 1987L. gaohuensis) in Epidemiology and ecology of rickettsial diseases in the People\u2019s Republic of China as a vector of O. tsutsugamushi [Listed Orientia tsutsugamushi-associated species . Host-seeking larvae were gathered from the ground and vegetation in Japan [in Japan .L. imphalum Vercammen-Grandjean and Langston, 1976O. tsutsugamushi, R. conorii, R. typhi, Rickettsia sp. and a novel bacterium Candidatus Rickettsia jingxinensis. Laboratory reared individuals originating from larvae captured in nature were also positive for Mycobacterium sp. Lehmann and Neumann, 1896 Infected larvae were obtained from the bodies of A. agrarius, B. indica, R. exulans, R. losea, R. rattus and R. tanezumi captured in Taiwan and Thailand [Species known to carry Thailand ,97,105.L. insulare Wei, Wang and Tong, 1989O. tsutsugamushi vectors in China [Listed among in China .L. intermedium O. tsutsugamushi. Positive larvae were obtained from A. speciosus, M. musculus and R. norvegicus as well as from the vegetation (prior to parasitic phase). Records come from China and Japan [Species associated with nd Japan ,108,109.L. kawamurai M. rufocanus and A. speciosus ainu were reported as O. tsutsugamushi-positive in Japan [Larvae parasitizing the gray red-backed vole in Japan ,107,110.L. keukenshrijveri O. tsutsugamushi [Unengorged larvae gathered from the ground by the black plates method in Malaysia tested positive for ugamushi .L. kitasatoiO. tsutsugamushi. Parasitic larvae were taken from A. speciosus and unengorged chiggers derived from the ground and vegetation in Japan [Species evidenced as positive for in Japan ,70,107.L. linhuaikongense O. tsutsugamushi. Positive parasites originated mostly from rodents: A. agrarius, M. musculus, R. norvegicus and the greater long-tailed hamster Tscherskia triton captured in China. Scrub typhus agent was also detected in a nymph reared in the laboratory from engorged larva [Known for association with ed larva ,113,114.L. murotoense O. tsutsugamushi vectors in Japan [Listed among in Japan ,107.L. orientale Orientia tsutsugamushi-positive parasitic larvae were found in South Korea and Russia (Primorsky Krai). Chiggers were captured on wild animals including A. agrarius, M. regulus and C. lasiura [ lasiura ,116,117.L. pallidumNagayo, Miyagawa, Mitamura and Tamiya, 1919O. tsutsugamushi, R. conorii and Rickettsia sp. Infected individuals were collected from the vegetation (unengorged larvae) and the following mammal hosts: A. agrarius, A. speciosus, B. indica, M. fortis, M. montebelli, M. regulus, \u2018C. triton\u2019 (most probably T. triton), R. exulans, R. losea, R. tanezumi and C. lasiura. Reports come from Japan, Russia (Primorsky Krai), South Korea and Taiwan. [Species reported as positive for Taiwan. ,119,120.L. palpale Orientia tsutsugamushi-positive species, larvae of which were collected from A. agrarius, A. speciosus, M. regulus, M. musculus, R. norvegicus, T. triton and C. lasiura. Laboratory reared nymph also tested positive for the presence of the pathogen. Records originate from China, Japan, Russia (Primorsky Krai) and South Korea [th Korea ,115,117.L. pavlovskyi O. tsutsugamushi, collected and examined in Russia (Primorsky Krai). Pathogen-positive individuals included parasitic larvae feeding on infected rodents and shrews: A. agrarius, \u2018C. triton\u2019 (most probably T. triton), the reed vole M. fortis and C. lasiura, along with nymphs reared in the laboratory [Species associated with boratory ,117,120.L. peniculatum Traub and Lakshana, 1966L. paniculatum) gathered with use of the black plate method in Thailand tested positive for O. tsutsugamushi [Unengorged larvae in the USA (North Carolina) turned out positive for Rickettsia sp. and species very closely related to R. conorii, R. felis and R. typhi [Parasitic larvae found on the white footed deer mouse R. typhi .L. rajasthanense Fernandes and Kulkarni, 2003Orientia tsutsugamushi-positive larvae of this species fed on R. rattus captured in India [in India .L. rubellum Wang and Liao, 1984O. tsutsugamushi vectors in China [Listed among in China .L. rupestre Traub and Nadchatram, 1967O. tsutsugamushi in Pakistan [Species found in mite pools positive for Pakistan .L. scutellare Nagayo, Miyagawa, Mitamura, Tamiya and Tenjin, 1921O. tsutsugamushi, R. typhi, R. felis, Rickettsia sp. as well as pathogens most closely related to R. akari Huebner, 1946 and R. australis Philip, 1950 as well as a novel species Candidatus Rickettsia leptotrombidium. Host-searching larvae were gathered from plants and soil while parasites were collected from the bodies of A. agrarius, A. agrarius chejuensis, A. speciosus speciosus, the small Japanese field mouse A. argenteus argenteus , B. indica, Eothenomys kageus Imaizumi, 1957, M. montebelli, M. regulus, M. musculus, R. exulans, R. losea, R. norvegicus, R. tanezumi, T. triton, Urotrichus talpoides hondonis, C. lasiura and S. murinus. Listed records originate from China, Japan, Malaysia, South Korea, Taiwan and Thailand [Species positive for Thailand ,125,126.L. sialkotense Vercammen-Grandjean and Langston, 1976O. tsutsugamushi vectors in China [Listed among in China .L. subintermedium O. tsutsugamushi vectors in India and Pakistan [Mentioned among Pakistan ,103.L. taishanicum Meng, Xue and Wen, 1983Orientia tsutsugamushi-positive larvae were collected from M. musculus and R. norvegicus in China. Among tested hosts, also A. argarius and T. triton were bacteria-positive [positive ,111.L. tosai Trombicula tosa) tested positive for O. tsutsugamushi. Larvae fed on M. montebelli and A. speciosus in Japan [Species O. tsutsugamushi-associated larvae (mentioned as L. zeta) were collected from the mice, including A. agrarius, in South Korea [th Korea ,116.Lorillatum Nadchatram, 1963Genus: Lorillatum sp.O. tsutsugamushi. Larvae parasitized rodents from R. rattus-complex in Thailand [Genus representatives were reported to harbor Thailand .Microtrombicula Ewing, 1950Genus: Microtrombicula sp.Candidatus Orientia chuto Izzard et al., 2010. Parasites collected from \u2018Micromys natalensis\u2019, in Kenya [Reported as positive for in Kenya .M. chamlongi Nadchatram and Kethley, 1974O. tsutsugamushi. Record from Thailand [Unengorged larvae collected from the black plates spread over the ground tested positive for Thailand .Miyatrombicula Sasa, Kawashima and Egashira, 1952Genus: M. kochiensis Sasa, Kawashima and Egashira, 1952Orientia tsutsugamushi-associated species. Unengorged larvae were gathered from the ground and vegetation in Japan [in Japan .Neoschoengastia Ewing, 1929Genus: Neoschoengastia sp.Epidemiology and ecology of rickettsial diseases in the People\u2019s Republic of China as a genus characterized by low rate infection with O. tsutsugamushi [Listed in ugamushi .Neotrombicula Hirst, 1925Genus: Neotrombicula sp.Candidatus Orientia chuto. Larvae were collected from \u2018Micromys natalensis\u2019, in Kenya. Reported also from Spain as associated with R. felis [Evidenced as positive for R. felis ,131.N. autumnalis Anaplasma phagocytophilum (Foggie 1949) , B. burgdorferi s.l. Johnson et al., 1984, B. garinii Baranton et al., 1992, B. valaisiana Wang et al., 1997, R. monacensis, R. helvetica, R. pavlovskyi and Rickettsia sp. Infected larvae were collected from rodents , birds (Aves: Passeriformes)), soricomorphs ), lizards , the Italian wall lizard P. siculus and the western green lizard Lacerta bilineata Daudin, 1802 (Reptilia: Squamata)) as well as from the vegetation. One case of infected nymph was reported too. Observations were made in Czech Republic, Germany, Italy, Russia, Slovakia, Spain and Ukraine [Individuals of the European harvest mite were reported to contain Ukraine ,135,136.N. autumnalis should be thoroughly verified after proper mounting on microscopic slides, due to considerable resemblance of this species to N. inopinata. Proven misidentification was reported from Turkey.Remarks: According to Stekolnikov et al. , all recN. carpathica Stekolnikov, 1996B. garinii and B. valaisiana. Larvae parasitized S. atricapilla in Czech Republic [Reported as carrier of Republic .N. inopinata B. garinii, B. valaisiana and Rickettsia spp. Parasitic larvae were gathered from S. atricapilla in Czech Republic and unengorged ones from the vegetation in Spain [Associated with in Spain ,137.N. japonicaO. tsutsugamushi-related species. Collected from wild rodents, mainly A. agrarius, M. fortis, \u2018C. triton\u2019 (most probably T. triton) and insectivorous C. laisiura, along with the host-questing larvae from the ground and vegetation. Records come from Japan, South Korea and Russia (Primorsky Krai) [Frequently mentioned as ky Krai) ,120,138.N. microti O. tsutsugamushi-positive species collected from rodents in Russia (Primorsky Krai) [Mentioned as ky Krai) .N. mitamurai O. tsutsugamushi carrying mites parasitizing rodents and shrews in Russia (Primorsky Krai) [Listed among ky Krai) ,116,138.N. nagayoi O. tsutsugamushi-positive species collected from rodents, including A. agrarius, in Russia (Primorsky Krai) and Korea [Mentioned as nd Korea ,139.N. pomeranzevi O. tsutsugamushi-associated. Parasites captured most probably from M. rufocanus and A. speciosus ainu in Japan and Russia (Primorsky Krai) [Larvae were reported as ky Krai) ,137,139.N. sadoensis Saito and Otsuru, 1959Orientia tsutsugamushi-positive representatives of the species were reported and taxonomically described from the Sado Island (Japan) [ (Japan) .N. tamiyai Trombicula tamiyai) as O. tsutsugamushi-positive species collected from rodents and shrews in Russia (Primorsky Krai) [Mentioned .N. vulgaris R. helvetica and R. monacensis. Gathered from Rickettsia-positive rodents: M. glareolus, A. flavicollis, M. arvalis and A. sylvaticus in Slovakia [Larvae of the species revealed the presence of Slovakia .Odontocarus Ewing, 1929Genus: Odontocarus sp.O. tsutsugamushi. Report from Thailand [Unengorged larvae captured by the method of black plates tested positive for Thailand .Parasecia Loomis, 1966Genus: Parasecia sp.Rickettsia sp. was detected in larvae of this genus parasitizing birds in Brazil [n Brazil . Quadraseta Brennan, 1970Genus: Q. trapezoides Candidatus Rickettsia colombianensi. Larvae were collected from the South American water rat Nectomys squamipes in Brazil [Parasite carrying a novel bacterium n Brazil .Sauriscus Lawrence, 1949Genus: S. sandovali Tecomatlana sandovali) taken from the sac-winged bat Saccopteryx bilineata tested positive for C. burnetii. Record from Panama [Larvae Candidatus Rickettsia colombianensi. Larvae were captured feeding on the montane grass mouse Akodon montensis Thomas, 1913 in Brazil [Mite associated with a novel bacterium n Brazil .Trombiculindus Radford, 1948Genus: T. variaculum Orientia tsutsugamushi-associated species, larvae of which were collected from R. exulans in Thailand [Thailand .Walchia Ewing, 1931Genus: Walchia sp.Orientia tsutsugamushi-positive chiggers of this genus were obtained from B. indica. Thailand [Thailand .W. chinensis O. tsutsugamushi. Larvae taken mostly from R. tanezumi flavipectus, captured in China [Known for carrying in China ,141.W. kritochaeta R. exulans, R. tanezumi, B. indica, B. berdmorei and the red spiny rat Maxomys surifer in Thailand [Species tested positive for the scrub typhus etiologic agent. Parasitic larvae were collected from Thailand .W. masoni Lepus brachyurus Temminck, 1845 ) in Japan were positive for bacterium related to O. tsutsugamushi, however, according to authors, the record is not fully confirmed [Larvae captured from wild hares O. tsutsugamushi. Collected from B. indica and M. surifer in Thailand [Larvae of the species contained genetic material of Thailand .W. minuscuta M. surifer in Thailand tested positive for O. tsutsugamushi. Species also known to harbor Borrelia sp. [Parasitic larvae found on elia sp. ,40.W. ogatai Sasa and Teramura, 1951O. tsutsugamushi [Host-questing larvae gathered from the vegetation in Japan tested positive for ugamushi .W. pacifica O. tsutsugamushi-associated larvae were obtained from rodents, mainly, A. agrarius, R. norvegicus and T. triton in China [in China ,113,114.The above records are graphically summarized in Trombiculidae spp.Bartonella spp., Borrelia spp., Francisella spp. Dorofe\u2019ev 1947 , Leptospira spp. Noguchi, 1917 and O. tsutsugamushi [Mycobacterium sp. was detected in trombiculids parasitizing rodents and insectivores from Thai populations [Metagenomic analysis of rodent-associated chiggers collected in Thailand showed that undetermined chiggers were infected with the following pathogens: ugamushi . Additioulations .Borrelia spp., C. burnetii-like bacterium and Candidatus Orientia chuto in trombiculids collected from the Eastern spiny mouse Acomys dimidiatus , the Yemeni mouse Ochromyscus yemeni , the king jird Meriones rex Yerbury and Thomas, 1895 and R. rattus [Pioneer survey on ectoparasites of rodents and related pathogens carried out in Saudi Arabia revealed the presence of . rattus ,144.A. agrarius and C. lasiura in South Korea indicated mites\u2019 association with Rickettsia sp., R. akari, R. australis, R. conorii, R. felis, R. japonica Uchida et al., 1992 and R. typhi [Research on pathogens associated with trombiculids parasitizing R. typhi .Occurrence frequency of particular bacteria (genera and species) as well as bacterial families associated with Trombiculidae are illustrated in Leptotrombidium nangiiL. tachensisL. waiganmensisEpidemiology and ecology of rickettsial diseases in the People\u2019s Republic of China and described as infected with O. tsutsugamushi at low rate [The three taxa were listed in low rate .Remarks: Species not listed in the reference checklists, even as synonyms.Neotrombicula shiraiiO. tsutsugamushi-associated mites in Japan [Listed among in Japan ,71.Neoschoengastia shiraii\u2019, a parasite of birds occurring in Japan, can be found but without mention of scrub typhus bacterium [Remarks: This combination has not been found in the current literature, even as a synonym. Reports on \u2018acterium . Leptotrombidium is characterized by the highest number of bacteria-positive species (38), followed by Neotrombicula (12) and Walchia (8) (Leptotrombidium spp. are positive for the highest quantity of pathogenic taxa (14), next is Neotrombicula (11) and Eutrombicula (7) , to name only the most frequent rickettsial species. Considerable incidence also characterizes Borreliaceae\u2014infection with Borrelia spp. was observed in 11 cases . This micula (7) . Rickett11 cases . Hereby ttsaemia ,54,133. utellare ,148, howBorrelia spp. spirochetes [Leptotrombidium spp feeding. Authors hypothesized that the canal structure might have been related to the mite\u2019s ability to acquire bacteria, as larvae of L. intermedium turned out to be pathogen-free [O. tsutsugamushi and L. intermedium. Moreover, Neotrombicula pomeranzevi, Miyatrombicula esoensis and Kepkatrombicula desaleri produce the longest feeding canals, thus penetrating host tissues relatively deep, albeit the ability to ingest pathogens by the two latter species still awaits confirmation in laboratory tests. On the other hand, H. zachvatkini and Leptotrombidium spp. Create shorter canals which widen in time and were reported as bacteria-positive quite frequently is their natural presence in organisms of Rodentia and Soricomorpha [Rickettsiales, the obligate intracellular parasites , are esprochetes ,154,155.rochetes ,156. Hasgen-free . This asequently . Cheladosiae too ,156. Concomorpha ,161,162,comorpha ,167,168.association between mites and pathogens has been deliberately applied as vectorship, i.e., capability of effectively transmitting bacteria to humans (or other vertebrates) is not proven for all pathogen-positive chigger species and the presence of microorganisms may be resulting from ingesting dissolved host tissues , especially when engorged larvae are preserved and tested shortly after being detached from the host. Confirmed vectors of Orientia spp., e.g., L. deliense, L. akamushi, L. scutellare or H. antarctica, meet the criteria formulated by Traub and Wisseman: natural infection with a pathogen, ability to infect a host , high prevalence in a given area and, tendency for parasitizing humans. The latter point regards of course only diseases plaguing people and it is not essential for the mechanism of vectorship as such. As Trombiculidae, unlike, e.g., Ixodidae or Macronyssidae, are parasitic once in a lifetime, to successfully transmit bacteria larvae have to acquire them via transstadial and transovarial transmission from the parental generation [Leptotrombidium spp. so far e.g., [Eutrombicula, Herpetacarus, Microtrombicula, Miyatrombicula, Neotrombicula, Odontocarus and Walchia genera along with the infected deutonymphs and successful experimental infections, indicate that the possibility of effective pathogen transmission remains high in a variety of chigger mite species.A term neration ,54. The ar e.g., ,20,21. AH. zachvatkini larvae were present in contrast to nine of A. latyshevi and one N. absoluta Schluger, 1966 larva. Significant disproportions in field-collected chiggers were also recorded during a survey performed in India\u2014the most common species L. deliense and L. insigne Fernandes and Kulkarni, 2003 combined totalled 9408 larvae, while the rarest\u2014Walchia sp. and Schoutedenichia sp. were 33 and single larva, respectively. Tamura et al., in turn, observed the following shares of mites collected in Japan: L. pallidum (56.6%), L. scutellare (13.6%), L. fuji (12.7%), G. saduski (10.5%), N. japonica (1.6%), L. kitasatoi (1.6%), L. palpale (1.4%), L. intermedium (1.1%), L. miyazakii Sasa, Sawada, Kano, Hayashi and Kumada, 1951 (0.1%), L. miyajimai (0.3%), N. tamiyai (0.02%), Eltonella ichikawai Vercammen-Grandjean, 1965 (0.1%) and C. ikaoensis (0.1%) [N. autumnalis and N. inopinata [Rickettsia-positive Eutrombicula sp. and Leptotrombidium sp., previously determined upon morphological criteria, with corresponding data in the GeneBank using the BLAST tool [c. 80 nominal species only). At the same time, obtaining COI sequences of L. imphalum and L. chaigraiensis led to separation of these species, formerly considered as one [One should bear in mind, yet, that detailed research on vector competence of the particular mites species is often hindered by two issues. The first one is extremely varied numbers of mites from particular species in collected samples\u2014ranging from thousands of individuals of the most common taxa, to single ones of the most infrequent . This is illustrated by results of chigger collection in NW Russia wherein thousands of s (0.1%) ,169,170.s (0.1%) . The secmnalis\u2019) . FurtherAST tool . This prd as one ,88.Orientia species\u2014Candidatus Orientia chiloensis. The pathogen was effectively transmitted to humans by H. antarctica [O. tsutsugamushi , detected in Trombiculidae occurring outside the \u2018tsutsugamushi triangle\u2019 come from Kenya and Saudi Arabia. From the latter country, O. chuto-positive patient was reported as well [Candidatus rickettsia colombianesi, Ca. rickettsia jinxinensis and Ca. rickettsia leptotrombidium) harbored by Trombiculidae, along with the most recent and the first ever findings of rickettsiae in chiggers from North Carolina (USA) [Identification difficulties should not suppress the research on pathogen transmission by Trombiculidae inasmuch the most accurate species determination can be achieved by simultaneous application of morphological and molecular tools, as it has been already implemented in some studies ,173,174.tarctica ,73,175. as well ,130,143.na (USA) only reana (USA) and can bacteria, chigger mites, detection, pathogen, spirochaetes, Trombiculidae, trombiculid terms. Collected records cover almost 100 years (from 1924 to 2022) of the research on the association between chiggers and bacterial pathogens, detected by means of microscopic, culturing, serological and molecular examinations performed worldwide but are not included in plots and calculations.The share of pathogen-associated trombiculids is low in comparison with the total number of nominal species comprising the Trombiculidae family. Nonetheless, so far revealed bacteria-positive mites are characterized by harboring differentiated bacterial species, vast geographical distribution and association with a variety of hosts. Moreover, the present summary also points at cases of relatively recently discovered novel bacterial species and localities wherein the discussed microorganisms were apparently absent to date. This knowledge, combined with the unwavering significance of zoonotic bacterioses and the recognized mechanisms of pathogens circulation in chigger populations, are premises that the actual number of Trombiculidae-bacteria associations is not limited to the cases presented. An assumption can be made that the continual microbiological testing of chiggers, especially when supported with the fast and highly effective technologies, will result in further findings."} +{"text": "In the published publication , there wAffiliation 2. Department of Plastic Surgery, College of Medicine, Yeungnam University, Daegu 38541, KoreaAffiliation 3. Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Yeungnam University, Daegu 38541, KoreaTae-gon Kim, Jun Sung Moon and Seung Min Chung were not included as authors in the original publication. The corrected Author Contributions Statement appears here.Author Contributions: Conceptualization, C.H.P. and I.W.; data curation, H.S. and J.P.; methodology, T.-g.K., J.S.M. and S.M.C.; investigation, T.-g.K.; writing\u2014original draft preparation, I.W.; writing\u2014review and editing, H.S.; supervision, C.H.P. All authors have read and agreed to the published version of the manuscript.The authors apologize for any inconvenience caused state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "Ceroxyela, and suggest that Isoxyela and Sinoxyela should be transferred to Gigantoxyelini.One new genus and two new species, described from new fossil specimens of northeastern China, enhance our knowledge of the Xyelidae in the mid-Mesozoic. A key to the genera of Angaridyelini and a table of known fossil species of Macroxyelinae are provided. After investigating various angles between Rs+M and 1-Rs for known fossil species of Macroxyelinae, we report that the angle and the length of 1-Rs are correlated. In addition, we believe that the tribe Ceroxyelini may have only one genus of Leptoxyela eximia gen. et sp. nov., and one new species, Scleroxyela cephalota sp. nov., are described and illustrated based on two well-preserved compression fossils from the Lower Cretaceous Yixian Formation and the Middle Jurassic Jiulongshan Formation of China, respectively. Leptoxyela eximia gen. et sp. nov. is placed in the tribe Angaridyelini, 1966 and Scleroxyela cephalota sp. nov. in the tribe Xyeleciini Benson, 1945; while both tribes are in the subfamily Macroxyelinae Ashmead, 1898 of Xyelidae. A key to the genera of Angaridyelini is provided. In addition, we investigated various angles between Rs+M and 1-Rs for known fossil species of Macroxyelinae, and we found the angle and the length of 1-Rs are correlated; however, we could not see any correlation between the angles and the fossil ages even within a tribe. Furthermore, based on Sc2 connected to R before Rs, the angle between Rs+M and 1-Rs, and the length of the first flagellomere, we believe that the tribe Ceroxyelini may have only one genus of Ceroxyela, and suggest that Isoxyela and Sinoxyela should be transferred to Gigantoxyelini.One new genus and species, Hymenoptera, one of four mega-diverse insect orders, comprises more than 155,000 described species and playThe earliest appearances of xyelids have been reported from the Middle or Upper Triassic of Kyrgyzstan , and the1 next to pterostigma, short and wide ovipositor and at least partially sclerotized pterostigma [Macroxyelinae are a common subfamily of Xyelidae in the Mesozoic and can easily be differentiated from all other subfamilies because of the following combination of characters: the sclerotized apical bridge between C and Rrostigma . Macroxyrostigma . Up to dScleroxyela, which enhance our knowledge of the Xyelidae in the Mesozoic of northeastern China.In this report, we describe a new genus and species as well as a new species of a previously erected genus Leptoxyela eximia gen. et sp. nov. The wing venation nomenclature used in this paper follows Huber and Sharkey (1993) . AntennaSystematic palaeontology.Order: Hymenoptera, Linnaeus, 1758.Suborder: Symphyta, Gerstaecker, 1867.Superfamily: Xyeloidea, Newman, 1834Family: Xyelidae, Newman, 1834Subfamily: Macroxyelinae, Ashmead, 1898Tribe: Angaridyelini, Rasnitsyn, 1966Leptoxyela, Dai, Rasnitsyn, and Wang gen. nov.Genus: Leptoxyela eximia, Dai, Rasnitsyn, and Wang sp. nov.Type species: Lepto-\u201d, meaning thin and referring to the long and thin terminal part of flagellum, and the generic name Xyela.Etymology: the generic name is a combination of Greek \u201c1 connected to C beyond level of Rs and Sc2 connected to R just before origin of Rs; Rs1 closer to pterostigma than to 1-Rs2 along wing margin; 1m-cu apparently longer than 2-Cu; ovipositor sheaths short and moderately wide.Diagnosis: Antenna with thread, longer than first flagellomere. Pterostigma sclerotized basally; 1-Rs slightly longer than half 1-M, shorter than half 2-Rs; ScSpecies included: type only.Leptoxyela gen. nov. is attributed to Macroxyelinae, based on the sclerotisation connecting C and R before pterostigma; short and moderately wide ovipositor sheaths, and further to Angaridyelini based on pterostigma sclerotized only basally. Within Angaridyelini, the new genus is similar to Nigrimonticola in having long antennal thread; Sc1 connected to C beyond level of Rs and Sc2 connected to R just before origin of Rs. It can be differentiated from Nigrimonticola by its longer 1m-cu (see Key below for details).Remarks: Key to the genera of Angaridyelini1.\u00a01-Rs longer than 2-Rs ..................................................................................................................Ophthalmoxyela Rasnitsyn, 1966.1-Rs shorter than 2-Rs A .......22.\u00a0Cell 1mcu twice as long as pterostigma. Sc lost ......................................................................Baissoxyela Rasnitsyn, 1969.Cell 1mcu at most 1.5 \u00d7 as long as pterostigma F. Sc dis33.\u00a02 connected to R just at Rs base .............................................................................................Sc42 connected to R before Rs base .Abdomen with nine segments visible, ovipositor sheath broad and short; first valvifers roughly triangular; second valvifers large, longer than first valvifers; ovipositor well preserved, first valvula as wide as second valvula.Tribe: Xyeleciini, Benson, 1945Scleroxyela, Zheng, Hu, D. Chen, J. Chen, Zhang, and Rasnitsyn, 2021Genus: Scleroxyela daohugouensis, Zheng, Hu, D. Chen, J. Chen, Zhang, and Rasnitsyn, 2021.Type species: Scleroxyelacephalota, Dai, Rasnitsyn, Shih, and Wang sp. nov.Species included: type species and Scleroxyela cephalota, Dai, Rasnitsyn, Shih, and Wang sp. nov. Material: CNU-HYM-NN-2021004, housed at the College of Life Sciences and Academy for Multidisciplinary Studies, Capital Normal University.kephalon\u201d, meaning head and referring to the large head.Etymology: the specific name is from Greek \u201cLocality and horizon@ latest Middle Jurassic , Jiulongshan Formation; Daohugou Village, Shantou Township, Ningcheng County, Inner Mongolia, China.Description : Male short, subvertical to R, shorter than 1-Rs and connected to R well before origin of Rs; anterior branch (Sc1) long, reaching C beyond origin of Rs; R distinctly bent before origin of Rs and greatly thickened before pterostigma; 1-Rs half the length of 1-M; 2r-rs ca. 1.5\u00d7 as long as 1r-rs; 3-Rs arched posteriorly; 1m-cu half the length of 3-CuA, roughly equal to 1cu-a; 3r-m about 1.3\u00d7 as long as 2r-m; M+Cu slightly curved in its basal third; CuP straight, extended to the top of cell 2a. Cell 1r about twice as long as 2r and 2.6\u00d7 as long as wide; cell 2r trapezoidal, length ratio of cells 1r:2r = 2:1; cell 1cua narrow and long, distinctly broader at M base, about 7.5 times as long as wide, and twice as long as cell 1mcu; cell 2mcu long and narrow, longer than 2rm and about 3.6 times as long as wide; cell 1a 1.75 times as long as 2a.Forewing (6.42 mm long) with pterostigma completely sclerotised, costal area obviously widened proximad base of Rs; Sc with two branches, posterior branch of Sc (ScHind wing with 1-Rs vanishing short (1r-m meeting Rs close to Rs base); limit between 1-M and 1r-m obscure; M+Cu nearly straight.Foreleg and middle leg incomplete, hind leg with coxa elongate, about 1.5\u00d7 as long as wide; trochanter small and trapezoidal; femur oval, slightly wider medially, about 4.6\u00d7 as long as wide; hind tibia long, about 1.1\u00d7 as long as femur; tarsi not preserved.Abdomen with nine segments visible, genitalia visible, hypopygium large, diamond-shaped; gonocoxa wide, subtriangular , apparently wider than gonostylus; gonostylus long, with distinct gonomacula.Scleroxyela cephalota sp. nov. can be assigned to the subfamily Macroxyelinae based on the pterostigma slerotised and with sclerotisation connecting C and R near pterostigma, to the tribe Xyeleciini based on Sc2 connected to R before Rs and 1-Rs at most half the length of 1-M, and to the genus Scleroxyela based on pterostigma completely sclerotized and Sc1 reaching C distinctly behind Rs. Within the genus, the new species differs from S. daohugouensis in having the head wider, pterostigma wider than 1r-rs length, Sc2 connected to R more distant from Rs base, and forewing shorter (6.42 mm long vs. 11.1 mm in S. daohugouensis). These differences are unlikely to be sexually dependent.Remarks. We describe one new genus and two new fossil species, from Huangbanjigou and Daohugou of China, respectively. Both Daohugou and Huangbanjigou are important insect deposits containing abundant, well-preserved insect fossils . The DaoCeroxyela Rasnitsyn, 1966), from 150\u00b0 to 170\u00b0 in the tribe of Macroxyelini, and from 145\u00b0 to 180\u00b0 in the tribe Gigantoxyelini.The angle between Rs+M and 1-Rs is usually obtuse in Macroxyelinae, but the angle varies among the tribes. The formation of angle between Rs+M and 1-Rs is discussed red in using a We try to compare and investigate the angle changes between Rs+M and 1-Rs for the tribes in the subfamily Macroxyelinae. We found that there are two trends in the degree of the angle allowing the creation of two informal groups of Macroxyeline tribes and . Note that some overlappings of the morphospaces of some tribes are recorded . InteresCeroxyela. Subsequently, Zhang and Zhang (2000) reported two genera, Sinoxyela and Isoxyela, which were also placed in tribe Ceroxyelini based on their pterostigma of the forewing being sclerotized and basally membranous. In this report, we believe that Isoxyela and Sinoxyela cannot be attributed to Ceroxyelini primarily based on these different characters: Sc2 meeting R before Rs for Isoxyela and Sinoxyela; the pterostigmal desclerotisation is less extensive than in Ceroxyela; the angle between Rs+M and 1-Rs is 120\u00b0 in Ceroxyela, strongly different from those of Sinoxyela (155\u00b0) and Isoxyela (157\u00b0); and the length of 1-Rs and the first flagellomere of Isoxyela and Sinoxyela are obviously different from those of Ceroxyela.The tribe Ceroxyelini was established by Rasnitsyn (1969) initially consisting of only one genus of Isoxyela and Gigantoxyela), to as long as it (Scleroxyela), to 0.6 times shorter than thread (Leptoxyela), and up to 0.4 times so (Ceroxyela). Based on the above study on the veins and antennae, we believe that the tribe Ceroxyelini may only consist of one genus of Ceroxyela, and that the genera Isoxyela and Sinoxyela should not be included in Ceroxyelini. We would suggest to transfer these two genera to Gigantoxyelini tentatively, based on the sclerotized pterostigma and basal Sc2 until more information is available. We also hope that there will be better phylogenetic results in the future to reveal the relationship within Ceroxyelini.The first flagellomere, an important diagnosis trait in Xyelidae , is alsoAs the most basal group of Symphyta in Hymenoptera, the family Xyelidae has a special status in the evolutionary history of the Symphyta ,8,9. TheLeptoxyela eximia gen. et sp. nov. and Scleroxyela cephalota sp. nov., based on two well-preserved compression fossils from the Lower Cretaceous Yixian Formation and the Middle Jurassic Jiulongshan Formation of China, respectively. Leptoxyela eximia gen. et sp. nov. is placed in the tribe Angaridyelini and S. cephalota sp. nov. in the tribe Xyeleciini; while both tribes are in Macroxyelinae of Xyelidae. After investigating various angles between Rs+M and 1-Rs for known fossil species of Macroxyelinae, we reported that the angle and the length of 1-Rs are correlated, however, we could not see any correlation between the angles and the fossil ages even within a tribe. In addition, we suggested that Isoxyela and Sinoxyela should be transferred to Gigantoxyelini and the tribe Ceroxyelini may have only one genus of Ceroxyela.We described"} +{"text": "Scorzonera in its revised circumscription is proposed.Subtribe Scorzonerinae contains 12 main lineages and approximately 300 species. Relationships within the subtribe, either at inter- or intrageneric levels, were largely unresolved in phylogenetic studies to date, due to the lack of phylogenetic signal provided by traditional Sanger sequencing markers. In this study, we employed a phylogenomics approach (Hyb-Seq) that targets 1,061 nuclear-conserved ortholog loci designed for Asteraceae and obtained chloroplast coding regions as a by-product of off-target reads. Our objectives were to evaluate the potential of the Hyb-Seq approach in resolving the phylogenetic relationships across the subtribe at deep and shallow nodes, investigate the relationships of major lineages at inter- and intrageneric levels, and examine the impact of the different datasets and approaches on the robustness of phylogenetic inferences. We analyzed three nuclear datasets: exon only, excluding all potentially paralogous loci; exon only, including loci that were only potentially paralogous in 1\u20133 samples; exon plus intron regions (supercontigs); and the plastome CDS region. Phylogenetic relationships were reconstructed using both multispecies coalescent and concatenation approaches. Overall, our phylogenetic reconstructions recovered the same monophyletic major lineages found in previous studies and were successful in fully resolving the backbone phylogeny of the subtribe, while the internal resolution of the lineages was comparatively poor. The backbone topologies were largely congruent among all inferences, but some incongruent relationships were recovered between nuclear and plastome datasets, which are discussed and assumed to represent cases of cytonuclear discordance. Considering the newly resolved phylogenies, a new infrageneric classification of Epilasia (Bunge) Benth., Geropogon L., Koelpinia Pall., Pterachaenia (Benth.) Stewart, Scorzonera L., Tourneuxia Coss., and Tragopogon L. is a polyphyletic assemblage and that its various clades are completely intermingled in phylogenetic trees with the traditionally accepted genera To evaluate the potential of the Hyb-Seq approach for resolving the phylogenetic relationships at inter- and intrageneric levels across the subtribe; (2) To test the hypotheses on phylogenetic lineages within the Scorzonerinae inferred through the molecular phylogenetic study based on nrITS and two plastid DNA markers in addition to comparative morphology and fruit-anatomy by Scorzonera in its former widest sense Kuth., Pterachaenia, Ramaliella Zaik et al., Scorzonera, Takhtajaniantha Nazarova, and Tragopogon. However, for Tourneuxia variifolia Coss., the only member of Tourneuxia, and Lipschitzia divaricata (Turcz.) Zaika et al., the only member of that genus, wet lab treatment did not yield sufficient reads for analysis. A total number of 152 samples from representatives of subtribe Scorzonerinae were included (Willemetia stipitata (Jacq.) Dalla Torre, Chondrilla ramosissima Sm.], Cichoriinae (Cichorium intybus L.), Hypochaeridinae , Lactucinae (Lactuca sativa L.), and Scolyminae . Herbarium specimens with the permission for DNA extraction for this study were kindly provided by the following herbaria: Botanic Garden and Botanical Museum Berlin (B), Ferdowsi University of Mashhad (FUMH), Ernst-Moritz-Arndt-Universit\u00e4t Greifswald (GFW), Komarov Botanical Institute of Russian Academy of Science St. Petersburg (LE), Staatliche Naturwissenschaftliche Sammlungen Bayerns, M\u00fcnchen (M), Shahid Bahonar University of Kerman (MIR), Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen (MSB), Moscow State University (MW), and Naturhistorisches Museum Wien (W). Wet laboratory work was undertaken in the Botanic Garden and Botanical Museum Berlin molecular lab and the Berlin Center for Genomics in Biodiversity Research (BeGenDiv) consortium genomics lab. Genomic DNA was extracted from dried leaf tissues, using the NucleoSpin Plant II kit and DNeasy Plant Mini Kit following the manufacturer\u2019s protocol. The total genomic DNA quantity was measured with a Qubit 2.0 Fluorometer . The quality of genomic DNA extractions was assessed for level of fragmentation and fragment size using a 0.9% (w/v) agarose gel. A total of 1 \u03bcg of genomic DNA in 60 \u03bcL was sheared to a target average fragment size of \u223c500 bp by sonicating for 55 s using a Covaris S220 . Sonication was not carried out for well-fragmented (<600 bp) genomic DNA samples extracted from herbarium specimens.The DNA libraries were prepared using the NEBNext Ultra II DNA Library Prep Kit for Illumina , following the standard protocol provided by the manufacturer. We followed the library preparation wet laboratory method described for the Berlin lab, provided by Carthamus tinctorius, Helianthus annuus, and L. sativa for the 1,061 loci of the COS by de novo assembly of mitochondrial genomes (L. sativa DQ_383816.1) to identify the more conserved regions between the total readpool and this initial reference and then assembled into contigs, yielding a new and gapped reference sequence. In the second step, the MITObim wrapper script uses the gapped reference to fish in the readpool for partly or fully overlapping reads. In the third step, the overlapping reads are mapped to the gapped reference sequence and incorporated, using MIRA again. The two last steps are iteratively repeated until stationarity of the mapped and assembled reads are reached (Cichorium intybus (NC_043842.1) and L. sativa (NC_007578.1) as references and, after reorganizing the sequence designation in the resulting GeSeq multi-fasta files to start with the sample designation, the Phyluce package , COS supercontigs, plastome CDS; Gelasia was selected as the outgroup for this dataset, and a total of 124 samples across the remainder of the subtribe were included as ingroup , COS supercontigs, and plastome CDS . The sam ingroup .The three types of datasets were analyzed separately under two principal approaches: (1) the multispecies coalescent approach , in whicC. arenaria as an outgroup using R and the package APE . We applied the default CAT-GTR and a discretized gamma distribution with four categories, which are computationally resource-intensive but have shown to perform well in inferring accurate branching patterns in genomic datasets and the species trees based on the concatenated matrix were conducted with ML using RAxML-NG, and tree inference with RAxML-NG can occasionally be misled by non-randomly distributed missing data , we alsodatasets . Convergdatasets , therefodatasets . SubsequS. hispanicus and C. arenaria) because this is the earliest diverging clade of the tribe in our sampling and the number of COS loci recovered for each sample ranged from 423 in S. laciniata DB 44268 to 1,041 in Pseudopodospermum picridioides DB 44329, with a mean of 968 loci of the total of 1,061 target loci in the set. A total of 897 COS loci and 832 COS supercontig loci were identified by HybPiper as loci containing potentially paralog sequences and removed from the datasets before analyses. After removing the spurious sequences of the matrices in the COS supercontigs dataset in trimAl and eliminating the loci with less than 50% taxa in both datasets, the OLS dataset and COS supercontigs datasets yielded 147 and 148 loci, respectively. The final concatenated OLS dataset had a length of 44,634 bp, of which 16,315 were parsimony informative (\u223c35%) and an average of 8% missing data per locus and plastome CDS datasets were performed under ML and Bayesian inference based on concatenated loci and under the multispecies coalescent model based on the individual gene trees \u20135. Treesa clades . CollapsIn general, deep tree branches were well-supported and the backbone topology was largely congruent in all inferences of each dataset , 4, whilTechnical details regarding phylogenetic analyses conducted on the COS contigs (OLS and ELS), COS supercontigs, and plastome CDS datasets are given in Overall, the phylogenetic inferences in this study based on the nuclear on-target and plastome off-target Hyb-Seq data revealed the same major clades as those inferred by The exemplary ancestral character state reconstruction for the seven pollen types on the nuclear backbone tree is provided in Epilasia, Gelasia, Geropogon, Koelpinia, Pseudopodospermum, Pterachaenia, Ramaliella, Scorzonera, Takhtajaniantha, and Tragopogon. Also, within Scorzonera, the same seven clades were resolved with full support confirmed the monophyly of subtribe Scorzonerinae and resolved the same major phylogenetic lineages of the subtribe as identified by support as in ZaS. albicaulis and S. angustifolia clades was resolved as sister to the S. renzii clade in ML-concatenation analyses of ELS with high support , whereas with distinctly lower support in those of OLS . Concerning the shallower nodes, the support for the sister group relationship of Ramaliella longipapposa DB 32214, and Ramaliella tortuosissima DB 44309 was improved in ML concatenation analyses of the ELS , compared to both ML concatenation analyses of the OLS , see Gelasia, Koelpinia, Pterachaenia, and Ramaliella (full support), and the others of Epilasia, Geropogon, Pseudopodospermum, Scorzonera, Takhtajaniantha, and Tragopogon . In the first clade, Gelasia was resolved as sister to a clade in which Ramaliella was sister to Pterachaenia , and these together as sisters to Koelpinia (full support) based on ML and Bayesian concatenated analyses .Regarding the relationships between the major clades, the backbone topology of the coalescent-based analyses shows single not statistically supported nodes or low support values for single clades , whereas always fully resolved nodes and fully or strongly supported clades in the concatenation approach . The 30%analyses . The bacupported . In the Geropogon and Tragopogon, was resolved as sister to Epilasia and this clade in turn as sister to Pseudopodospermum . In the coalescent analysis, the relationships between these three clades were unresolved, forming a polytomic structure and they, in turn, were sister to the S. rupicola clade with full support. The coalescent analysis revealed the same topology, however, with lower support for some clades or between Koelpinia and Ramaliella (72 BS-P). A clade including the remainder of the subtribe was split into two well-supported clades: one comprising Epilasia, Geropogon, Pseudopodospermum, Takhtajaniantha, and Tragopogon , the other the Scorzonera lineage. The same topology was revealed for the relationships of these lineages in the concatenated and coalescent trees, however, the nodes had lower support in the coalescent analysis. Within the Scorzonera lineage, the concatenation and coalescent inferences showed congruence in the backbone topology of major clades including the Podospermum clade, S. purpurea clade, Scorzonera s.typ. clade, S. albicaulis clade, and S. angustifolia clade, but different positions of the S. renzii and S. rupicola clades across trees.Analyses of the supercontig data matrices using ASTRAL and concatenated ML approaches (unpartitioned and partitioned data matrices) resulted in largely similar topologies for the phylogenetic backbone of the Scorzonerinae. The backbone nodes were well-supported in the concatenated analyses, while the multispecies coalescent analysis revealed some nodes that were not statistically supported and otherwise had lower nodal support . A fullyIn contrast to the nearly complete backbone congruence between the various analyses of the nuclear datasets, the corresponding tips in shallow nodes generated most cases of topological incongruences and nodal support differences for species relationships \u20134. We wiGelasia, Geropogon, Takhtajaniantha, the S. rupicola, and S. renzii clades, and the clade comprising Koelpinia, Pterachaenia, and Ramaliella.The phylogenetic backbones of the four analyses based on the plastome CDS matrix were largely congruent with each other . AnalyseGeropogon was resolved as sister to the remainder of the subtribe, also with full support in all analyses; Tragopogon was not represented in the plastome datasets. ML and Bayesian concatenated analyses inferred a sister relationship between a clade containing Takhtajaniantha as sister to Scorzonera and another clade including Epilasia, Gelasia, Koelpinia, Pseudopodospermum, Pterachaenia, and Ramaliella , while in the coalescent analysis, the relationship between Takhtajaniantha and the Scorzonera lineage was not statistically supported and the clade, therefore, collapsed, resulting in a trichotomy , with Gelasia as sister to Epilasia and Pseudopodospermum; in the ML and Bayesian trees, the sister group relationship between Epilasia and Pseudopodospermum was resolved , while in the ASTRAL tree, this relationship was not statistically supported . The relationship of the Scorzonera s.typ. clade, as sister to the clade including the Podospermum, S. purpurea, and S. renzii clades, was resolved in both the Bayesian and ML trees but not statistically supported in the ASTRAL tree, and the relationship of the S. renzii clade, as sister to the clade formed by Podospermum and the S. purpurea clades was resolved in all analyses . However, the sister relationship of Podospermum and the S. purpurea clade was recovered with low support . This was expected because the non-coding intron regions possess a great amount of variation and are less sensitive to selective pressures, such as selection-driven convergence . The res%. This wKoelpinia and Takhtajaniantha with a basic number of x = 6 or 7 . = 6 or 7 . However= 6 or 7 . TherefoPseudopodospermum, Takhtajaniantha, and Scorzonera to the Tragopogon-Geropogon-Epilasia clade.The extension of our original COS dataset to include loci with paralog warnings that were found to be based on allelic variation only, allowed us to investigate the impact of an increase from 147 loci by 64 loci or c. 43% to 211 loci (in the extended data set ELS) on the phylogenetic reconstruction. The higher number of loci brought about a corresponding increase in variable and PI sites, whereas their percentages remained almost constant . ML concThe first plastid DNA phylogeny of the Scorzonerinae by Sonchus comparing phylogenetic reconstruction based on the protein-coding CDS only, with one based on the entire plastome, and The success in using the off-target reads for assembling plastid genomes has been shown to depend significantly on the spiking of the post-capture library with the unenriched pre-capture library . Among tIt seems at least a precautionary measure to extend the application of the multispecies coalescent approach also to the plastid DNA matrix. However, our reconstructions based on the protein-coding CDS show no hard topological incongruences that would indicate the presence of significantly discordant plastid gene trees, apart from generally lower support of the branches and a consequently lower resolution of the ASTRAL tree . This reOur phylogenetic reconstructions corroborate the monophyly of the Scorzonerinae and fully resolved its backbone phylogeny . MoreoveGelasia, Koelpinia, Pterachaenia, and Ramaliella and the other of Pseudopodospermum, Takhtajaninatha, Epilasia, Tragopogon, Geropogon, and Scorzonera and Scorzonera and Tragopogon, corresponding to the origin of the two principal clades, in the late Early Miocene (c. 17\u201318 mya). This age estimation for the diversification of the subtribe was corroborated by Scorzonera and Tragopogon are estimated by Tragopogon with its >150 species, estimated the origin of that genus later in the Late Miocene c. 7.4 mya (3.7\u201311.6 HPD). The highest species diversity of Tragopogon is centered in the mountainous habitats around the Paratethys basin, where the Black, Caspian, and Aral Seas represent relics of the former Paratethys Sea. They estimated its diversification to have taken place rather late and rapidly from 2.6 mya onward, thus, well after the Messinian Salinity Crisis in the late Miocene between 5.3 and 5.96 mya, which brought about a dramatic aridization of the entire region . Furthermore, a rather recent diversification seems likely given the shallow genetic differences within these major lineages (see below).e region . RegardiTourneuxia, which was inferred as the first diverging clade of the subtribe in the plastid DNA tree by Geropogon, represented by two samples, as sister to the remainder of the subtribe or the S. purpurea-Podospermum-Scorzonera s.str. clade . Consequently, in many cases, infrageneric and interspecific relationships received no or low statistical support and showed incongruences among analyses, which, considering their lack of support, are not meaningful. Some species groups, in contrast, were consistently well-supported as monophyletic. In the following, we focus on these well-supported species groups, discussing their internal relationships, morphological synapomorphies, and possible occurrence of cytonuclear discordance.In principle, our study confirmed that the Hyb-Seq approach is useful to resolve close relationships at interspecific levels. However, branch support strongly decreased for internal nodes closer to the tips compared to backbone relationships. We interpret this because of the presumed young age of the speciation within the major lineages, which was inferred for Gelasia: Both nuclear and plastid DNA analyses strongly support the Gelasia lanata group composed of G. flaccida (S. flaccida Rech. f.), G. lanata (L.) Zaika et al. (G. psychrophila (Boiss. & Hausskn.) Zaika et al. , although the relationships between these species remained unresolved , G. wendelboi (S. wendelboi Rech. f.), and G. xylobasis (S. xylobasis Rech. f.) is also monophyletic in both nuclear and plastid analyses Zaika et al. and G. cinerea (Boiss.) Zaika et al., which is consistent with the nuclear DNA analyses that placed the latter two species with the G. persica group in a moderately to the highly supported clade Zaika et al. Cass., which provides the type of the generic name, including G. doriae Zaika et al., G. ensifolia (M.Bieb.) Zaika et al., G. biebersteinii (Lipsch.) Zaika et al., G. caespitosa (Pomel) Zaika et al., and G. callosa (Moris) Zaika et al. were usually resolved with low to moderate support only but fairly consistently in both nuclear Zaika et al., P. ferganicum (S. ferganica Krasch.), P. papposum (DC.) Zaika et al., P. picridioides (Boiss.) Hatami, and P. limnophilum (S. limnophila Boiss.), as monophyletic with high support Zaika et al., P. brevicaule (Vahl) Zaika et al., P. baeticum (DC.) Zaika et al., and P. reverchonii (Debeaux & Hervier) Zaika et al. Zaika et al., which also includes, apart from the name-giving species, P. calyculatum (Boiss.) Zaika et al., P. bicolor (S. bicolor Freyn & Sint.), and P. violaceum (D. F. Chamb.) Zaika et al. Zaika et al., T. grubovii (S. grubovii Lipsch.) and T. austriaca (Willd.) Zaika et al. Zaika et al. and T. pseudodivaricata (Lipsch.) Zaika et al. Zaika et al., T. ikonnikovii (Krasch. & Lipsch.) Zaika et al., T. pusilla Nazarova, and T. tau-saghyz (Lipsch. & G. G. Bosse) Zaika et al.Scorzonera s. typ. clade: Among the four species of this clade, all nuclear and plastid analyses support the sister group relationship of S. radiata Fisch. ex Ledeb. and S. humilis L. well and bracteal leaves below the capitula.Podospermum clade: In all nuclear and plastid analyses, the species relationships within the Podospermum clade are largely unresolved. The only congruent interspecific topology in all nuclear analyses and both plastid ML-concatenation analyses is the sister group relationship of S. meshhedensis (Rech. f.) Rech. f. and S. songorica (Kar. & Kir.) Lipsch. & Vassilcz. E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera flaccida Rech. f., Fl. Iran. 122: 73. 1977.Gelasia persica (Boiss. & Buhse) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera persica Boiss. & Buhse in M\u00e9m. Soc. Imp. Naturalistes Moscou 12: 139. 1860.Gelasia subaphylla (Boiss.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera subaphylla Boiss., Diagn. Pl. Orient., ser. 1, 7: 8. 1846.Gelasia veratrifolia (Fenzl) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera veratrifolia Fenzl in Flora 26: 399. 1843.Gelasia wendelboi (Rech. f.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera wendelboi Rech. f., Fl. Iran. 122: 66. 1977.Gelasia xylobasis (Rech. f.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera xylobasis Rech. f., Fl. Iran. 122: 66. 1977.Pseudopodospermum bicolor (Freyn & Sint.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera bicolor Freyn & Sint. in \u00d6sterr. Bot. Z. 43: 266. 1892.Pseudopodospermum ferganicum (Krasch.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera ferganica Krasch. in Trudy Bot. Inst. Akad. Nauk SSSR, Ser. 1, Fl. Sist. Vys\u0161. Rast. 1: 180. 1933.Pseudopodospermum lacerum E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera lacera Boiss. & Balansa in Boissier, Diagn. Pl. Orient., ser. 2, 5: 116. 1856.Pseudopodospermum limnophilum (Boiss.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera limnophila Boiss., Diagn. Pl. Orient., ser. 1, 7: 7. 1846.Pseudopodospermum nivale (Boiss. & Hausskn.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera nivalis Boiss. & Hauskn. in Boissier, Fl. Orient. 3: 765. 1875.Pseudopodospermum tunicatum (Rech. f. & K\u00f6ie) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera tunicata Rech. f. & K\u00f6ie in Biol. Skr. 8,2: 196. 1955.Ramaliella microcalathia (Rech. f.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera tortuosissima var. microcalathia Rech. f. in Ann. Naturhist. Mus. Wien 55: 291. 1944 \u2261 Scorzonera microcalathia (Rech. f.) Rech. f. in Anz. \u00d6sterr. Akad. Wiss., Math.-Naturwiss. Kl. 98: 248. 1961.Takhtajaniantha grubovii (Lipsch.) E. Hatami, N. Kilian & K.E. Jones, comb. nov. \u2261 Scorzonera grubovii Lipsch. in Novosti Sist. Vyssh. Rast. 18: 229. 1981.Revised infrageneric classification of ScorzoneraScorzonera by Maintaining the circumscription of Scorzonera sect. Rupicolae1. E. Hatami, N. Kilian & K.E. Jones, sect. nov. \u2013 Type: S. rupicola Hausskn.Diagnosis. Suffruticose, dense pulvinate-caespitose perennial; stem with few or reduced leaves; capitula few on a single stem, easily falling; achenes attenuated at the apex.Note.S. rupicola was resolved already by Scorzonera. Moreover, S. rupicola has no close allies in the genus.Scorzonera sect. Renzianae2. E. Hatami, N. Kilian & K.E. Jones, sect. nov. \u2013 Type: S. renzii Rech. f.Diagnosis. Uppermost leaves filiform, spreading, subtending the capitula; capitula with short peduncles or subsessile in a racemiform synflorescence; phyllaries thick membraneous, subkeeled by \u00b1 prominent midrib.Note.S. renzii was resolved as the only species of the \u201cS. renzii clade\u201d in Scorzonera. Additionally, our analyses show this species to have no closer allies.Scorzonera sect. Piptopogon3. C. A. Mey. ex Turcz. in Bull. Soc. Imp. Naturalistes Moscou 21(3): 97. 1848 \u2261 Scorzonera subg. Piptopogon (C. A. Mey. ex Turcz.) C. D\u00edaz & Blanca in Anales Jard. Bot. Madrid 43: 330. 1987. \u2013 Type: Scorzonera macrosperma Turcz. ex DC. [= S. albicaulis]Achyroseris Sch. Bip. in Nov. Actorum Acad. Caes. Leop.-Carol. Nat. Cur. 21: 165. 1845. \u2013 Type: Achyroseris macrosperma (Turcz. ex DC.) Sch.Bip. [=S. albicaulis Bunge]= Scorzonera sect. Macrospermae Nakai in Rep. Inst. Sci. Res. Manchoukuo, ser. 1, 6: 168. 1937 \u2261 Scorzonera ser. Macrospermae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 719. 1964. \u2013 Type: Scorzonera albicaulis Bunge= Scorzonera ser. Acanthocladae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 722. 1964. \u2013 Type: Scorzonera acanthoclada Franch.= Scorzonera ser. Bracteosae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 720. 1964. \u2013 Type: Scorzonera bracteosa C. Winkl.= Scorzonera ser. Franchetianae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 721. 1964. \u2013 Type: Scorzonera franchetii Lipsch.= Scorzonera ser. Pauciflorae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 721. 1964. \u2013 Type: Scorzonera turkestanica Franch.= Scorzonera ser. Tragopogonoideae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 720. 1964. \u2013 Type: Scorzonera tragopogonoides Regel & Schmalh.= Scorzonera sect. Turkestanicae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 720. 1964. \u2013 Type: Scorzonera turkestanica Franch.= Diagnosis. Perennial herbs or subshrubs; leaves graminoid; capitula with 4\u201312 flowers only; achenes without carpopodium, beaked or at least attenuate at apex; pappus dirty yellow, caducous; pollen with 24 lacunae.Note. All nuclear and plastid analyses support the sister relationship of the S. angustifolia and S. albicaulis clades and the members of these clades also share morphological similarities, particularly having the same pollen type and apically attenuate to beaked achenes. The section has been recognized for a long time. It was also resolved as a separate clade by S. angustifolia L.Scorzonera sect. Scorzonera4. Scorzonera sect. Parviflorae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 79. 1964 \u2261 Scorzonera ser. Parviflorae Lipsch. in Bobrov & Tzvelev, Fl. URSS 29: 720. 1964. \u2013 Type: Scorzonera parviflora Jacq.= Scorzonera sect. Radiatae Nakai in Rep. Inst. Sci. Res. Manchoukuo, ser. 1, 6: 169. 1937. \u2013 Type: Scorzonera radiata Fisch. ex Ledeb.= Diagnosis. Leaves entire; capitula solitary or by a few only; inner phyllaries with apical red or blackish spots; achenes without carpopodium.Note. The typical section includes only four species: Scorzonera aristata, S. humilis, S. parviflora, and S. radiata (inclusion assumed by Scorzonera sect. Podospermum5. (DC.) Benth. in Bentham & Hooker, Gen. Pl. 2: 532. 1873 \u2261 Podospermum DC. in Lamarck & Candolle, Fl. Fran\u00e7., ed. 3, 4: 61. 1805, nom. cons. \u2261 Scorzonera subg. Podospermum (DC.) Lipsch., Fragm. Monogr. Gen. Scorzonera 1: 7. 1935. \u2013 Type: Scorzonera laciniata L.Scorzonera sect. Purpurea Lipsch., Fragm. Monogr. Gen. Scorzonera 2: 104. 1939. \u2013 Type: Scorzonera purpurea L.= Diagnosis. Leaves (at least some) pinnately divided, more rarely graminoid; phyllaries subapically often corniculate; achene with conspicuous tubular carpopodium; achene surface mostly glabrous or somewhat hairy.Note. The sister-group relationship of the S. purpurea and Podospermum clades was resolved with high support in all nuclear analyses and received at least weak to moderate support also in the plastid DNA analyses, and the presence of a tubular carpopodium in the achenes is a synapomorphy for the Podospermum-S. purpurea clade. We take this as justification for treating them in a single section. Within this section, the members of the S. purpurea clade are, nevertheless, set apart by their caudex with (instead of lacking) blackish-brown fibrous leaf sheath residues, graminoid leaves (instead of having at least some pinnately divided leaves), and pink or purplish (instead of yellow) flowers. These morphological differences may, however, be taken as justification to treat both clades alternatively as separate sections.The datasets presented in this study can be found in online repositories. The names of the repositories and accession numbers are given in the NK and KJ designed the project. KJ and EH performed the laboratory work and generated data. NK and EH conducted post-sequencing data processing and phylogenetic analyses, discussed the results, and wrote the manuscript. KJ commented on and revised the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "A promising scientific field is health monitoring and associated technology. A standard testing method to evaluate and identify heart issues is the electrocardiogram (E.C.G.) and diagnose cardiovascular diseases (CVDs). E.C.G. monitoring technologies are becoming more and more prevalent in publications at an exponential rate. E.C.G.\u00a0is the most crucial tool for screening cardiology and other medical specialities. Twelve leads can be recorded by traditional E.C.G. equipment, while current E.C.G. systems allow for extra leads also with fewer electrodes. Furthermore, \u201csmart\u201d gadgets allow patients to take an E.C.G. at residence. Presenting different ischemia-related symptoms on the E.C.G. by the most recent recommendations. Presentation of contemporary E.C.G. systems and their possible benefit in identifying ischemia-related E.C.G. symptoms based on recent study findings. The identification of ischemia E.C.G. abnormalities can be facilitated and optimised by current E.C.G. systems using vector-based electrocardiography. Although they can be effective for documenting transient E.C.G. abnormalities, especially inside the S.T. segment, smart non-vector-based devices for patients are primarily beneficial for the diagnosis of arrhythmias and cannot substitute the 12-lead E.C.G. for the diagnosis of ischemia. The electrocardiogram (E.C.G.) is inexpensive and easily accessible, but because of its alleged limited specificity, its utility as a screening tool for early detection of athletes with a cardiac condition in danger of immediate cardiac death is contentious. The interpreting parameters have been continuously evolving over the past 10 years as various efforts have been made to better the separation between healthy and pathological E.C.G. abnormalities in athletes. Electrocardiographic abnormalities that are unrelated to cardiac electrical activity are known as electrocardiographic artefacts. E.C.G.\u00a0elements, including the baseline and waves, can become altered as a result of artefacts. Acute myocardial infarction (MI) is a word coined for a match of coronary assault, which is caused by the deposition of plaques or cholesterol in the inner surface of the coronary arteries resulting in decreased blood flow to the heart and scarring the cardiac muscle mass due to insufficient oxygen supply\u00a0. Though The majority of MI with non-obstructive coronary artery (M.I.N.O.C.A.) patients who experience an acute myocardial attack/infarction with S.T. segment rise from the baseline typically have a pre-existing coronary or myocardial aetiology, most frequently plaque disruption or myocarditis\u00a0. Acute pST-segment elevationCases of S.T.-segment upliftment from baseline in MI with S.T.-segment upliftment from the baseline in the anterior and anteroposterior territories, and less frequently, concurrent S.T.-elevations in the anterior and inferior electrocardiography\u00a0leads. To identify this cardiac emergency, which frequently requires urgent coronary revascularisation, accurate interpretation of the E.C.G. is essential. Additionally, E.C.G. improves prognostic value and helps localise the artery connected to the infarct\u00a0. BecauseQ-waveQ-waves may indicate acute MI when seen on an\u00a0E.C.G.\u00a0There is no distinction between transmural and non-transmural infarction in the E.C.G. alterations. On the other hand, a Q-wave's existence or absence corresponds with several features of a patient's post-MI clinical history and hence has predictive significance. Congestive heart failure is more likely to worsen Q-wave infarctions while they are being treated in the hospital\u00a0. CongestPR segment depressionSignificant P.R.-segment depressed > or = 1.2 millimetres in the inferior leads was linked to an uncomfortable hospital stay and a subpar short-term prognosis in acute inferior MI. These individuals had a high chance of developing heart free-wall rupture, atrioventricular block, and supraventricular arrhythmias\u00a0. When thReciprocal T-wave changesThe behaviour of main T-wave abnormalities following exercise does not modify the interpretation of the ischemic alterations, according to exercise-induced T-wave normalisation studies. T-wave abnormalities are typically non-specific. However, isoproterenol treatment prevents post-MI T-wave modifications while treating a variety of functional and neurogenic T-wave abnormalities\u00a0. A thallT-wave inversionInverted T waves provide diverse anatomical lead groups with varied prognostic data. A higher risk of CHD is associated with a T-wave reversal in the lateral\u00a0and anterior\u00a0lead groups, and an increased risk of death is associated with lateral T-wave reversal. It was discovered that the inferior lead group's inverted T-wave was a harmless occurrence\u00a0. It is cTable Normal E.C.G.\u00a0has 12 leads which are used to measure the cardiac abnormalities in a person. There is a baseline in E.C.G., P-wave, Q.R.S. complex, and T-wave. The basic analysis of acute pericarditis and acute MI\u00a0can be diagnosed on the E.C.G.It can also be differentiated based on some factors in E.C.G.\u00a0The S.T.-segment upliftment denotes the rise of the S.T.-segment portion from the baseline. If the elevation of the S.T. segment is convex at the top of the elevated line, it is diagnosed as an acute MI, which is further studied in the limb for precisely conforming to the artery that is blocked, while in the case of the S.T. segment elevation if the elevated segment forms the concave curve at the top of the elevation, it is diagnosed as acute pericarditis. Q-wave is the starting negative bend of the rise to the Q.R.S. complex. Q-wave is the representation of the depolarisation of the ventricular in E.C.G. Q-wave is absent in the E.C.G.\u00a0of patients suffering from acute pericarditis, while the Q-wave is present with no or minimal changes in the patient suffering from sudden MI. The P.R. segment is the amount of time that passes between the atrium and ventricle depolarising. One of the most crucial elements in the diagnosis of acute pericarditis, along with depression, is the P.R. segment in the P.R.\u00a0segment is the most widely presented feature in E.C.G.\u00a0of the patient who is suffering from acute pericarditis, but on the other hand, the P.R.-segment depression is one of the rarest phenomena presented by the patients of acute MI. T-wave represents ventricular myocardium repolarisation. Reciprocal T-wave is a very abnormal change of T-wave in the aVL, which is very typically transmural. These reciprocal T-wave changes are usually not presented in the E.C.G.\u00a0of the patient with acute pericarditis. At the same time, the reciprocal T-wave changes are considered one of the most important changes in E.C.G.\u00a0for the diagnosis of acute MI in patients. Inversion of T-wave is well-defined as the negative movement of T-wave in more than two contagious leads, excluding the leads like III, aVR, and V1. This T-wave cannot be considered an important factor for the differentiation of acute pericarditis and acute MI, as it is seen in both patients suffering from the above disorders. But the important thing is that it is seen only after the S.T.-segment upliftment is normalised in the E.C.G.\u00a0of the patient suffering from the above disorder."} +{"text": "Cyprinus carpio var. communis , was evaluated by conducting a 10 week growth experiment. Casein-gelatin-based test diets representing six graded levels of vitamin A were designed and fed to the triplicate group of fish at 08:00 and 16:00\u2009hrs at the rate of 4% body weight per day. Growth parameters like live weight gain (LWG %), feed conversion ratio (FCR), protein efficiency ratio (PER), specific growth rate (SGR), and body protein deposition (BPD) improved significantly (P < 0.05) with each elevated dietary vitamin A level and found maximum growth rate along with the best- FCR at 0.11\u2009g/kg diet. Dietary vitamin A levels also significantly (P < 0.05) affected haematological parameters of the fish. Highest haemoglobin (Hb), erythrocyte count (RBC), haematocrit content (Hct %), and lowest leucocyte count (WBC) were observed at 0.11\u2009g/kg vitamin A fed diet compared to all the diets. Highest protein and lowest fat content were observed in the group of fingerlings fed with 0.11\u2009g/kg vitamin A containing diet. Blood and serum profile also showed some significant (P < 0.05) differences with elevating concentration of dietary vitamin A levels. Serum parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cholesterol values decreased significantly (P < 0.05) at 0.11\u2009g/kg vitamin A fed diet compared to control diet. However, except albumin the other electrolytes improved significantly (P < 0.05) and maximal values of these parameters were also evident at 0.11\u2009g/kg of vitamin A fed diet. Better value of TBARS was found in the group that fed 0.11\u2009g/kg vitamin A diet. Hepatosomatic index and condition factor improved significantly (P < 0.05) with fish fed at optimal dose 0.11\u2009g/kg of vitamin A diet. Based on quadratic regression analysis of LWG%, FCR, BPD, Hb, and calcium values of C. carpio var. communis against the varying levels of dietary vitamin A, an optimum growth, best FCR, higher BPD, Hb, and Ca values lie in the range of 0.10 to 0.12\u2009g/kg diet, respectively. The data generated during this study would be important in developing vitamin A balanced feed for successful intensive culture of C. carpio var. communis.Vitamin A requirement in fingerling common carp, Species compliable, nutritionally balanced formulated feed is prerequisite for profitable aquaculture. The development of such type of feed depends on complete information regarding dietary nutritional requirements and their respective availability in the feed ingredients \u20133. AmongAmong the fat-soluble vitamins, first fat-soluble vitamin to be recognized is vitamin A, which is considered a vital micronutrient required for growth of fish and exists in three forms, namely, retinal, retinol, and retinyl esters , 10. In C. carpio communis , O. niloticus , S. brasiliensis , hybrid grouper, E. fuscoguttatus \u00d7 E. Lanceolatus , O. niloticus , but lower than C. carpio var. communis . The difference in the vitamin A requirements may be due to varying methodological approaches and assessment criteria used such as species and size of fish, feeding environment, and measures of management.Species living in water must contend to a range of environmental factors including temperature, pressure, salinity, and oxygen availability as well as pollution concentration that influence nutrient requirements; hence, there occurs variation from those species living on land \u201343. Unli as well , 47\u201349. 31\u2009g/kg, ], M. ambC. carpio var. jain, Yang et al. [O. niloticus, Guimaraes et al. [For the assessment of the overall health, nutritional status, and balance in water of various fish species, haematological parameters act as a main diagnostic tool in aquaculture . Fish hag et al. and O. ns et al. . This mis et al. . Anothers et al. \u201361. Quans et al. , 63. In s et al. and Wu es et al. .C. carpio var. communis occurred due to inadequate or excessive supplementation of vitamin A in the diet. Same outcome was reported by the study of C. auratus [M. amblycephala [Paralichthys olivaceus [C. idellus [The physiological and pathological changes in fish happened due to many factors both exogenous and endogenous, affected by balanced feed and temperature, as evident in serum biochemical parameters of fish measuring health, nutritional status, and the ability to adapt to environmental changes . Stress auratus , M. amblycephala , Japaneslivaceus , and C. idellus . Serum p idellus , 71. In idellus . In our idellus . Electro idellus . Glucose idellus .C. carpio var. communis showed significant impact on proximate composition. Moisture, crude protein, and fat contents varied significantly. It is clearly visible in the results that fish fed basal diet showed highest fat content and lowest protein content, when compared to other group of fishes fed elevated levels of dietary vitamin A; the reason might be that fish fed basal diet preferred protein as an energy source than fat. Decreasing pattern of body fat concentration in fish fed diet containing higher levels of vitamin A than fish fed basal diet has also been reported in the past by other workers like Ornsrud et al. [C. carpio, Jeyaraj et al. [E. coioides, Yang et al. [A. Schrenckii, Wen et al. [C. idellus [In the present study, feeding varying levels of dietary vitamin A to d et al. , Mohamedd et al. , Hernandd et al. , Battistd et al. and Wu ed et al. . Also rej et al. , E. coiog et al. , and stun et al. showed s idellus .Morone chrysops\u00d7 M. saxatilis, Hemre et al. [Salmo salar, Ornsrud et al. [M. amblycephala, Liu et al. [E. coioides, Yang et al. [Mycteroperca tigris \u00d7 E. lanceolatus, Liang et al. [A. Schrenckii, Wen et al. [R. quelen, Battisti et al. [M. tigris \u00d7 E. lanceolatus, Liang et al. [The liver is a major storage organ involved with vitamin A metabolism and homeostasis . In fishe et al. , Salmo sd et al. , M. amblu et al. , E. coiog et al. , and Mycg et al. . The reag et al. , 80. As g et al. , enhanceg et al. , 83. In n et al. and highi et al. and M. tg et al. when fedM. amblycephala; contrary to this, Wen et al. [A. schrenckii exhibited poor appetite. Hernandez et al. [P. olivaceus fed with basal diet without supplemental vitamin A. Haung et al. [S. Sihama, when fed control diet and poor appetite when fed with diet containing higher concentration of dietary vitamin A.Vitamin A is among those nutrients which when absent or superfluous can do damage to the biological health . Eliminan et al. reportedz et al. also repg et al. reportedC. carpio var. communis to attain maximal growth and best feed conversion. Proximate composition, antioxidant capacity, haematology, and serum profile of C. carpio var. communis improved significantly with the optimum inclusion of vitamin A. Based on quadratic regression analysis of LWG, FCR, BPD, Hb, and Ca data against varying levels of dietary vitamin A, 0.11\u2009g/kg vitamin A is optimal for growth of fingerling C. carpio var. communis. The data generated during this study would be important in developing vitamin A balanced feed for successful intensive culture of C. carpio var. communis.The results of the study shows the importance of dietary vitamin A inclusion for fingerling"} +{"text": "Artemisia herba-alba methanolic extract monotherapy and combination therapies on the in vitro growth of several Babesia and Theileria parasites in vitro and mice was investigated in this study.The effect of A. herba-alba either in vitro or in vivo. Hematological parameters in the treated mice were analyzed using a Celltac MEK-6450 computerized hematology analyzer.Fluorescence assay using SYBR Green I stain was used to evaluate the antibabesial efficacy inhibitory of Artemisia herba-alba reduced the growth of Babesia bovis, Babesia bigemina, Babesia divergens, Theileria equi, and Babesia caballi in vitro in a dose-dependent manner. The in vitro inhibitory impact of A. herba-alba on B. divergens and B. caballi cultures was amplified when combined with either diminazene aceturate (DA). In B. microti-infected mice, a combination therapy consisting of A. herba-alba and a low DA dose inhibited B. microti growth significantly (p < 0.05) better than treatment with 25 mg kg\u22121 DA.A. herba-alba, when paired with a modest DA dose, could be a promising medicinal plant for babesiosis treatment.These data show that Babesia and Theileria are tick-borne parasites that infect animals\u2019 erythrocytes, causing enormous economic losses in the agricultural industry and worldwide trade [Babesia bovis (B. bovis) and Babesia bigemina (B. bigemina) in cattle [Theileria equi (T. equi) and B. caballi in horses [B. microti or a gerbil infected with Babesiadivergens is used for drug evaluation [de trade ,2. Clinide trade ,4. The in cattle or Theiln horses . Becausealuation ,7.Artemisia herba-alba, commonly known as desert or white wormwood, is used in folk medicine to treat various diseases [A. herba alba as antidiabetic, antimicrobial, antimalarial, acaricidal [A. herba-alba extract\u2019s antibabesial efficacy is yet to be determined. As a result, in the current investigation, we evaluated the antipiroplasm of A. herba-alba against the growth of B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi in vitro, and B. microti in mice.For many years, the standard therapies for babesiosis were diminazene aceturate (DA) and imidocarb dipropionate ,9. Howevdiseases ,13. Sevearicidal ,14,15, aaricidal ,17. HoweThe Animal Care and Use Committee at Obihiro University of Agriculture and Veterinary Medicine approved all of the study\u2019s experimental protocols . The trials followed the Fundamental Guidelines for the Proper Conduct of Animal Experiments and Related Activities at Academic Research Institutions published by the Ministry of Education .A. herba-alba was dissolved in 50 ml of 99.8% methanol and incubated at 30\u00b0C for 3 days [\u00aeRotavaporR-200/205, Flawil, Switzerland), and a freeze-drying vacuum system [A. herba-alba methanolic extract toxicity to bovine and equine erythrocytes was assessed using 25 mg/ml as previously published study [r 3 days . The finMO, USA) ,20. The ed study . A. herba-alba against B. bovis (Texas strain) [B. bigemina (Argentina strain) [B. divergens (German strain) [B. caballi [T. equi (U.S. Department of Agriculture) [A. herba-alba utilized ranged from 0.025 to 30 mg/ml. The in vitro study used DA, a routinely used antibabesial medication, as a positive control agent with concentrations ranging from 0.1 to 10 \u00b5g/ml [A. herba-alba) and DDW (0.02% for DA) served as negative experimental controls . RBCs infected with 1% parasitemia of bovine and equine Babesia/Theileria parasites were cultured in 96-well plates for 4 days without daily medium replacement, using 2.5% hematocrit (HCT) for B. bovis and B. bigemina parasites and 5% HCT for other Babesia and Theileria parasites, as previously established [in vitro regrowth after ceasing A. herba-alba therapy was monitored using a viability assay, as described earlier in our study [The chemotherapeutic efficacy of strain) , B. bige strain) , B. dive strain) , B. caba caballi , and T. culture) was inveculture) ,22. The ablished . All scrur study .A. herba-alba and DA was tested against in vitro cultures of bovine Babesia and horse piroplasm parasites having the highest IC50 values, for B. bovis and T. equi, as previously detailed [The combination therapy of detailed ,26. All A. herba-alba in vivo inhibition assay for B. microti (Munich strain) [The strain) in 25 fe strain) . Five grp-value less than 0.05.A one-way analysis of variance test was used in GraphPad Prism to discover significant differences between the analyzed groups . Statistical significance was defined as 50s, A. herba-alba has the most significant impact on the growth of T. equi and B. bigemina, followed by B. bovis (According to the computed ICB. bovis . 0.025 m < 0.05) . 0.10 mg T. equi . Further < 0.05) .Theileria equi and B. bigemina in vitro were suppressed at doses of 0.5 and 1 mg/ml, respectively, in the following viability test between the DMSO-treated positive control well and the untreated wells shows that the diluent did not affect the efficacy of the A. herba-alba methanolic extract. Furthermore, compared to nontreated erythrocytes, pretreatment of erythrocytes with a high dose of A. herba-alba methanolic extract at 25 mg/ml did not affect parasite growth pattern or erythrocyte morphology (data not shown).ity test . The parrba-alba . With 10 reduced . The lacB. divergens and B. caballi, different combinations of A. herba-alba and DA were tested. On the growth of B. divergens, highest concentration of A. herba-alba (0.75 IC50) demonstrated a synergistic interaction with high doses of DA (0.75 and 0.50 IC50) . Low dosarasites . Such fiA. herba-alba was tested in mice for its ability to suppress B. microti in vivo. Within the presence of 500 mg kg\u22121A. herba-alba monotherapy, the greatest fluorescence values within the A. herba-alba-treated groups reached a mean of 1702 at 12 days p.i. [This study looked at how andidate . Similara longa) .A. herba-alba as an agent with antimalarial activity [Plasmodium and Babesia parasites have striking biological similarities. Taken together, the antioxidant effect of A. herba-alba [Babesia is usually associated with increased levels of free radicals and oxidative stress markers [The efficacy of activity ,15 may erba-alba may expl markers , which iA. herba-alba exhibited no effect on bovine or horse RBCs. Additionally, A. herba-alba has been safely consumed for centuries without adverse effects. Previous studies reported the safe use of A. herba-alba in rats at >2 gm/kg [A. herba-alba in mice was greater than 5,000 mg/kg [In the current investigation, very high concentrations of >2 gm/kg ,31. Such00 mg/kg .in vitro inhibitory activity of A. herba-alba and its safety have prompted us to study the inhibitory effect of A. herba-alba when taken alone or in combination with DA in mice. In our investigation, the in vitro inhibitory effect of A. herba-alba, combined with DA, against the growth of B. divergens and B. caballi was strengthened. These results are similar to the in vitro inhibitory effects of myrrh oil/DA [in vivo study, the inhibition of B. microti growth caused by A. herba-alba/DA is nearly similar to 56.35% and 53.25% inhibition rates for 85 mg kg\u22121 PYR combined with 10 mg kg\u22121 DA, respectively [A. herba-alba when used as monotherapy or in combination therapy against the growth of B. microti in mice, further studies are required to determine the LD50 of this herbal extract in cattle before its application under field conditions.The h oil/DA , allicinh oil/DA , and thyh oil/DA . In an iectively . AlthougB. bigemina and T. equi were the most sensitive Babesia species to Artemisia herba-alba\u2019s in vitro inhibitory action, followed by B. bovis. A. herba-alba was co-administrated with DA, a synergistic interaction against the in vitro growth of B. divergens was observed. The emitted fluorescence signal in the blood of mice treated with a combination therapy containing lower doses of A. herba-alba and DA was significantly reduced. Furthermore, a combination of A. herba-alba/DA therapy was used to correct hematological variables and treat hemolytic anemia caused by babesiosis. By overcoming the toxicity and resistance associated with long-term use of the antibabesial drug DA, A. herba-alba may be beneficial in treating animal piroplasmosis.In conclusion,"} +{"text": "The genus Xanthomonas comprises phytopathogenic bacteria which infect about 400 host species, including a wide variety of economically important plants. Xanthomonas oryzae pv. oryzicola Swings et al., 1990 is the causal agent of bacterial leaf streak (BLS) being one of the most destructive bacterial diseases of rice. BLS symptoms are very similar to those of bacterial blight caused by closely related Xanthomonas oryzae pv. oryzae. X. o. pv. oryzae and X. o. pv. oryzicola and often occur in rice f ields simultaneously, so separate leaves may show symptoms of both diseases. The quarantine status and high severity of the pathogen require a highly eff icient, fast and precise diagnostic method. We have developed an assay for Xanthomonas oryzae pv. oryzicola detection using real-time polymerase chain reaction (qPCR) and PCR amplicon sequencing. The DNA samples of X. o. pv. oryzae and X. o. pv. oryzicola were obtained from the collection of CIRM-CFBR (France). To evaluate the analytical sensitivity of the assay, a vector construct based on the pAL2-T plasmid was created through the insertion of X. o. pv. oryzicola target fragment (290 bp). Primers and a probe for qPCR were selected for the hpa1 gene site. They allowed identifying all the strains the sequences of which had been loaded in the GenBank NCBI Nucleotide database before November 11, 2021. The SeqX.o.all sequencing primers were selected for the hrp gene cluster sequence, namely for the nucleotide sequence encoding the Hpa1 protein, the sequencing of which allows for eff icient differentiation of X. oryzae species. The analytical specif icity of the system was tested using the DNAs of 53 closely related and accompanying microorganisms and comprised 100 % with no false-positive or false-negative results registered. The system\u2019s analytical sensitivity was not less than 25 copies per PCR reaction. Its eff icacy has been conf irmed using f ive different qPCR detection systems from different manufacturers, so it can be recommended for diagnostic and screening studies. Bacteria Xanthomonas Dowson, 1939 are spread worldwideand able to infect at least 400 kinds of plants includingthose of high economic importance . Currently,27 species of this family have been known, many of whichdemonstrate high levels of virulence and specificity in certainkinds of plants . Bacterial leaf streak (BLS) is consideredto be one of the most devastating diseases caused in riceby Xanthomonas oryzae pv. oryzicola ,Swings et al., 1990 .The disease results in 8 to 32 % of yield loss and isregarded as a serious problem in rice-producing countries. Since the damage doneby BLS can seriously threaten the world\u2019s food security, Xanthomonas oryzaepv. oryzicola was included in List 1 of harmful quarantineorganisms that are not present in the EEU territory as wellas in List A1 of the European and Mediterranean PlantProtection Organization (EPPO) that considers the bacteriaas quarantine ones( EPPO for the EU under Contract 90/399003. Data Sheets on QuarantinePests. https://gd.eppo.int/download/doc/530_ds_XANTOR_en [Accessed:23.11.2021]). Despite the fact that BLS is believedto have been detected for the first time in 1918 in the Philippines,its pathogen was identified only in 1957 in China. For the time being, BLS spreadis limited to the tropical and subtropical parts of Asia,Northern Australia and a part of Western Africa . The pathogen isabsent in the Russian Federation despite cases of infection . https://www.cabi.org/isc/[Accessed: 23.11.2021].)in the southern part of the country and the Russian Far East . According to the EPPO ReportingService, no cases of X. o. pv. oryzicola infection have beenregistered since 1994.Oryza sativa L., 1753, commonly known as Asian rice,is a typical host plant for X. o. pv. oryzicola. In addition,it affects some weed cereals and several other cultivatedplants such as Poaceae including Leersia spp., Leptochloaspp., Oryza spp., Paspalum scrobiculatum, Zizania,Zoysiaspp. . The bacteria mainly spread through infected seedsas well as due to mechanical damage. In case of smallplants, infection occurs through wind, raindrops, wateringor after contacting infected plant material .In plants, X. o. pv. oryzicola reproduce in the substomatalcavity where they get through the stomata to affectthe intercellular space of the parenchyma. However, theydo not get as far as the xylem and their spread is limitedby the mesophyll tissue\u2019s apoplast . The early stageof infection is characterized by small watery interveinalstrokes that later transform into bacterial effusion . The veins act as barriers preventing the pathogen\u2019sfurther spread and extending a leaf\u2019s affected areasalong its length, so they can merge later. In case of severeinfection, BLS becomes difficult to differ from the bacterialburn caused by Xanthomonas oryzae pv. oryzae, anotherquarantine bacterial species. Visual identification can alsobe complicated by favorable environmental conditions andplant resistance ,since both species can infect rice fields at the same time.The objective of the presented study was to develop andtest an assay for genetic detection and diagnostics of theXanthomonas oryzae pv. oryzicola pathogen using realtime polymerase chain reaction (qPCR) and PCR ampliconsequencing.The presented study was carried out at the BiotechnologyCollective Use Center of the All-Russian Research Instituteof Agricultural Biotechnology and Syntol LLC. As qPCRpositive controls, the DNA samples of the Indian typicalstrain of X. o. pv. oryzae (2532) and Malaysian pathotypeof X. o. pv. oryzicola (2286) from the French Collectionof Plant Associated Bacteria wereused. For the last pathotype, a draft whole genome assemblywas obtained . X. o. pv. oryzae\u2019sgeographic distribution is limited to the territories of Asia,Africa and North America, while that of X. o. pv. oryzicola\u2013 to the countries of Asia and Africa. Selecting the targetstrains, we relied upon the customs statistics of rice importto Russia and according to their data 31.7 % of importedrice in 2018 was supplied by India, followed by Thailand,Pakistan and Kazakhstan.In design of oligonucleotides for qualitative detection ofX. o. pv. oryzicola DNA, the hpa1 gene region was used.As many other gram-negative pathogens, X. o. pv. oryzicolahas the type III secretion system (T3SS) being amolecular syringe with which the bacteria deliver effectorproteins directly into the host cell cytosol . The T3SS and its secretedcomponents promote a hypersensitive response (HR) inresistant plants and plants not being the main host for thepathogen. The system is coded as hrp, a hypersensitivityand pathogenicity gene , the main operon of which is composed of more than20 genes in several transcription units that contain the hrp,hrc and hpa genes . Theoligonucleotides were synthesized by Syntol LLC usingtheir expendables. To design the qPCR and PCR ampliconsequencing reactions, reaction buffer B-009 was used.The buffer had the following component concentrations:3 mmol of MgCl2, 0.25 mmol of dNTP, and 2.5 \u0435. \u0430.of polymerase with antibodies to inhibit ferment activity(Syntol LLC). When designing the oligonucleotides, wemade sure the annealing temperature was 60\u201362 \u00b0\u0421 for theprimers and 64\u201367 \u00b0\u0421 \u2013 for the probe with 3\u2032-GC-clamp.The multiparameter analysis of the properties of theselected primers was performed using such online applicationsas Thermofisher Multiple Primer Analyzer (https://www.thermofisher.com), Promega Biomath Calculator \u2013Tm for Oligos Calculator (https://worldwide.promega.com), Oligonucleotide Properties Calculator (http://biotools.nubic.northwestern.edu). The qPCR fluorescence- gglabelledprobe incorporated a FAM dye attached to theprobe\u2019s 5\u2032 end. The RTQ-1 dye attached to the probe\u2019s 3\u2032 endserved as a quencher. The primer concentration in reactionmixture was 800 nM, and 400 nM \u2013 in the probe. The qPCRreaction\u2019s repeatability and reproducibility was assessedusing the following detection systems: ANK-M , QuantStudio 5 ,CFX-96 , DTprime 5 , Rotor-Gene 6000 . The obtainedresults were considered positive if the fluorescence signallevel exceeded the threshold of 10 % module difference ofthe lowest and highest signals.To verify the analytical sensitivity of the assay, a vectorpAL2-T-based structure with a 290 bpsinclusion of X. oryzae pv. oryzicola was designed. Ligationwas carried out after the PCR product was purifiedusing the ColGen DNA purification kit (Syntol LLC). Todesign the vector-based structure, a T4 DNA ligase buffer(Thermo Fisher Scientific) was used. The plasmid DNAwas impregnated into Escherihia coli bacteria (Migula1895) through thermal shock. The vector\u2019s presence wasattested using the PCR-colony method with the standardM13 primers followed by 1.5 % agarose-gel visualization.Plasmid DNA separation was carried out using a PlasGenreagent kit (Syntol LLC). The obtained circular plasmidwas processed with the NotI restriction enzyme (ThermoFisherScientific), its concentration measured in a Quantusfluorometer . To test the analyticalsensitivity of the designed assay, qPCR to dissolvethe plasmid were replicated 2 and 4 times. The analyticspecificity of the designed primers and probes was testedusing the DNAs of 53 closely related and accompanyingmicroorganisms .Bioinformatic analysis and data processing were performedusing the UGENE and AliView(Sweden) software solutions.To sequence X. o. pv. oryzicola\u2019s DNA, a primer coupleincluding seqX.o.all_F 5\u2032-TCTTTGAACACACAATTCGGCGG-3\u2032 and seqX.o.all_R 5\u2032-TGG AGAATCTCTCCGACGATA-3\u2032 was designed. The amplification programof PCR amplicon sequencing reaction included primarydenaturation (5 min at 95 \u00b0\u0421); cyclic denaturation (15 sat 95 \u00b0\u0421); annihilation (40 s at 60 \u00b0\u0421); cyclic elongation(36 cycles of 30 s at 72 \u00b0\u0421); final elongation (5 min at72 \u00b0\u0421). The sequencing was carried out using a Nanofor 05genetic analyzer (IAI RAS).The search for nucleotide sequences in GenBank NCBIfound 208 of them to belong to the Xanthomonas familyincluding 20 strains of X. o. pv. oryzicola. During sequencealignment performed in AliView, qPCR oligonucleotideswere selected for the regions of the hpa1 target gene conservativeto X. o. pv. oryzicola in such a way that the selected primers\u2019 attachment sites were strictly specific and enabledthe detection of all the target\u2019s stains the DNA sequencesof which had been loaded in the GenBank NCBI databasebefore 11.11.2021. Table 1 demonstrates the primer andprobe sequencies for X. o. pv. oryzicola diagnostics, selectedfor its hpa1 gene regionThe analytic specificity of the assay was tested using53 DNA samples of closely related and accompanyingmicroorganisms from different collections that included9 DNA samples of the bacteria belonging to the Xanthomonasfamily. The samples were obtained from collections:\u2013 of the All-Russian Center of Plant Quarantine and FederalService for Veterinary and Phytosanitary Surveillance\u2019sdivisions: Ralstonia solanacearum 0023, 0027,0029, 0030, Erwinia amylovora, Clavibacter michiganensissubsp. sepedonicus 0140, 0028, 0244, C. m.subsp. michiganensis 0240, 0241, 0242, 0243, X. o. pv.oryzae 0227, X. phaseoli, Pectobacterium carotovorumsubsp. carotovorum 0141, 0168, P. atrosepticum 0142,Dickeya solani, Xylophilus ampelinus 0124, Pantoeastewarti, P. st. subsp. indologenes, P. aglomerance,Candidatus Liberibacter, Acidovorax citrulli;\u2013 CIRM-CFBP collection, France: P. st. subsp. indologenesCFBP 3614, C. m. subsp. nebraskensis CFBP 2405,CFBP 3491, Curtobacterium f laccumfaciens pv. f laccumfaciensCFBP 3418, C. f l. pv. poinsettiae CFBP2403, C. f l. pv. oortii CFBP 1384, X. axonopodis pv.phaseoli CFBP 2534;\u2013 Leibniz Institute DSMZ-German Collection of Microorganismsand Cell Cultures GmbH, Germany: X. gardneriDSM 19127, X. perforans DSM 18975, P. wasabiaeDSM 18074, X. euvesicatoria DSM 19128, X. vesicatoriaDSM 22252, X. translucens pv. translucens DSM18974, P. cacticida DSM 21821, P. betavasculorumDSM 18076, D. dadantii subsp. dieffenbachiae DSM18013, D. d. subs. dadantii DSM 18020, D. paradisiacaDSM 18069, D. chrysanthemi DSM 4610, D. zeae DSM18068, P. c. subsp. odoriferum DSM 22556;\u2013 Singerta Company\u2019s collection (Russia): C. m. subsp. michiganensis,Agrobacteria spp., X. campestris pv. campestris,X. translucens pv. translucens;\u2013 All-Russian Microorganism Collection of G.K. SkryabinInstitute of Microorganism Biochemistry and Physiology: C. m.subsp.insidiosus \u0412\u041a\u041c \u0410\u0441-1402\u0422, C. m. subsp. nebraskensis\u0412\u041a\u041c Ac-1404\u0422, Pseudomonas savastanoi \u0412\u041a\u041c\u0412-1546;\u2013 All-Russian Collection of Industrial Microorganisms ofKurchatov National Research Center \u2013 GosNIIgenetika: C. albidum \u0412\u041a\u041f\u041c \u0412-1834.The primers and probe\u2019s analytic specificity for theabovementioned sample set was 100 %. All the samples containingX. o. pv. oryzicola DNA came positive, which wasconfirmed by sequencing. No false-positive results wereregistered including those for the DNA of X. o. pv. oryzae,which is a closely related variant of the target pathogen.For testing the assay\u2019s analytical sensitivity, the initialconcentration of the plasmid with X. o. pv. oryzicola insertionof 13 ng/\u03bcl or 3 \u00d7 109 copies/\u03bcl was used. qPCR in aseries of seven dilutions was performed as four 10-timedilutions, first in double repeat, and then in quadruplerepeat starting from the fifth series . After the firstdilution, the plasmid concentration reduced to 3 \u00d7 105 copies/\u03bcl. Starting from 150 copies, all the following dilutionseries were additionally titrated as 2 \u00d7 10n, 5 \u00d7 10n, 7 \u00d7 10nin quadruple repeat. For a series of seven 10-time dilutions,the kinetic curve slope comprised A = \u20132.671, andthe correlation ratio, R2 = 0.989. A stable specific signalwas observed down to 25 copies in the reaction mixture.In case of 10-time dilution of X. o. pv. oryzicola DNA, the assay showed lower sensitivity \u2013 down to 43 copies in thereaction mixture.The designed assay was tested using five qPCR detectionsystems from Russian and foreign manufacturers . As a matrix, a series of 10-time dilutionsof thepathogen\u2019s DNA was applied. The kinetic curve slopecomprised \u0410 = 3.00\u20133.67, the correlation ratio, R2 = 0.997\u20131.000, and the efficiency, \u0415 = 87\u2013116 %. The thresholdvalue difference comprised \u00b1 1 cycle, which was due to thefeatures of the systems\u2019 design and their threshold cyclecomputation algorithms.To test the primer pair enabling for Sanger sequencing diagnostics, direct PCRwas performed. As a matrix, the DNAs of X. o. pv. oryzae(2532) and X. o. pv. oryzicola (2286) were used as wellas a 1:1 bacterial DNA mixture to imitate joint infection.To differentiate the two closely related bacterial species,a region from 2 288 483\u20132 288 778 bps characterizedby a large number of nucleotide changes relative to thereference sequence CP050113.1 from the NCBI GenBankdatabase was used. Comparison of X. o. pv. oryzae andX. o. pv. oryzicola\u2019snucleotide sequences and their mixture can be seen in Fig. 3 where peaks C (X. o. pv. oryzicola)and G (X. o. pv. oryzae) match unlike the sequencing resultsfor each of the agents. Bioinformatic analysis of theobtained sequences confirmed they could infect a host bothindividually and jointly.Alignment of the obtained nucleotide sequences in themixture of DNA X .o. pv. oryzae and X. o. pv. oryzicoladetected 19 nucleotide changes relative to the referencegenome CP050113.1 (Table 3)Apart from the nucleotide changes listed in the Table 3,a three-nucleotide insertion in X. o. pv. oryzicola (in position2288667 bps) and a three-nucleotide deletion in X. o.pv. oryzicola (in position 2288702 bps) were found relativeto the reference X. o. pv. oryzae genome .The specific primer placement on X. oryzae enablesanalyzing pathovariant sequences to detect joint infectionby two closely related bacteria and indicate their species.The obtained nucleotide sequences made it possibleto confirm the cultures\u2019 relation to the collected strainsin relation to the genome data base. Alignment of the sequencesfrom the data base enabled us to understand certainintraspecific diversity of the X. o. pv. oryzae strains thatcame from Africa. At the same time, X. o. pv. oryzicola\u2019sdiversity was not that high and limited to a single SNP perstudied region of the hpa1 gene cluster. Despite the geneticpolymorphism of the population of bacterial infections inrice, the designed sequencing and qPCR primers make itpossible to detect all isolates irrespectively of the originof the material included in the Nucleotide NCBI database.Most of the procedures to detect X. o. pv. oryzae areapplicable for X. o. pv. oryzicola as well. Their identification begins with selecting the samples with clear infectionsymptoms for further cultivation in a nutrient solution.The method has its drawbacks since the colonies of bothbacteria grow slowly in isolation media. Another problemis the presence of dominating kinds of bacteria andbacterial antagonists that prevent proper observation ofthe target ones. Division of X. oryzae\u2019s two pathovariantsis possible due to their phenotypical features, inductionsymptoms, serological test, fingerprinting (polyacrylamidegel electrophoresis) and phagotyping results .Restriction fragment length polymorphism changes allowone to observe the almost compete genetic diversity ofisolates and their origin . However,this technique has a number of significant disadvantagessuch as insufficient sensitivity and specificity; high laborintensity that prevents the method from being used in diagnosticand industrial laboratories. For that reason, PCRhas become the key method for detection of the X. oryzaebacteria .Current assays allow for X. oryzae detection in general,and further separation into pathovariants requires a standardPCR assay with species-specific primers recommended bythe EPPO and All-Russian Center of Plant Quarantine, theresults of which are to be sequenced. The EPPO protocolfor X. o. pv. oryzae and X. o. pv. oryzicola identificationrecommends the TXT/TXT-4R primers to be used. To detectX. oryzae DNA using qPCR, it is recommended to use theX.o.F/X.o.R primers devised by the All-Russian Center ofPlant Quarantine . To separate the twopathovariants, qPCR can be performed using the PF/ PRprimers and the TaqMan probe that have been specificallydesigned to detect X. o. pv. oryzae .In 2021, the All-Russian Center of Plant Quarantinecarried out an interlaboratory comparison to detect BLSin rice (21XOO). 16 reference centers and interregionalvet laboratories took part and successfully passed a test todetect the disease using the Xanthomonas oryzae pv. oryzicola-RT assay we have designed.The designed assay enables the detection of BLS agents inrice. Being a reagent kit for qPCR, is also equipped with theseqX.o.all_F/R primers for PCR amplicon sequencing thatdetect X. oryzae in cases of individual and joint infection.The system allows for robust screening of quarantinableproducts and confirms obtained qPCR results with DNAsequencing. 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DOI10.1128/JB.182.7.1844-1853.2000.Zou L.F., Wang X.P., Xiang Y., Zhang B., Li Y.R., Xiao Y.L.,Wang J.S., Walmsley A.R., Chen G.Y. Elucidation of the hrpclusters of Xanthomonas oryzae pv. oryzicola that control thehypersensitive response in nonhost tobacco and pathogenicityin susceptible host rice. Appl. Environ. Microbiol. 2006;72(9):6212-6224. DOI 10.1128/AEM.00511-06."} +{"text": "Wheatgrass (Th. intermedium) has been traditionally used in wheat breeding for obtaining wheat-wheatgrass hybrids and varieties with introgressions of new genes for economically valuable traits. However, in the 1980s in the United States wheatgrass was selected from among perennial plant species as having promise for domestication and the development of dual-purpose varieties for grain and hay. The result of this work was the creation of the wheatgrass varieties Kernza and MN-Clearwater . In Omsk State Agrarian University, the variety Sova was developed by mass selection of the most winter-hardy biotypes with their subsequent combination from the population of wheatgrass obtained from The Land Institute. The average grain yield of the variety Sova is 9.2 dt/ha, green mass is 210.0 dt/ ha, and hay is 71.0 dt/ha. Wheatgrass is a crop with a large production potential, benef icial environmental properties, and valuable grain for functional food. Many publications show the advantages of growing the Kernza variety compared to annual crops in reducing groundwater nitrate contamination, increasing soil carbon sequestration, and reducing energy and economic costs. However, breeding programs for domestication of perennial crops are very limited in Russia. This paper presents an overview of main tasks faced by breeders, aimed at enhancing the yield and cultivating wheatgrass eff iciency as a perennial grain and fodder crop. To address them, both traditional and modern biotechnological and molecular cytogenetic approaches are used. The most important task is to transfer target genes of Th. intermedium to modern wheat varieties and decrease the level of chromatin carrying undesirable genes of the wild relative. The f irst consensus map of wheatgrass containing 10,029 markers was obtained, which is important for searching for genes and their introgressions to the wheat genome. The results of research on the nutritional and technological properties of wheatgrass grain for the development of food products as well as the differences in the quality of wheatgrass grain and wheat grain are presented. Climate change is an urgent problem affecting food security,since in the arid agricultural landscapes of Africa, Asia, and theSouth America cereals yield is sharply decreasing, in particularthat of maize, wheat, and sugar beetroot .The traditional agricultural system based on the cultivationof annual crops implies the usage of pesticides and moldboardplow tillage, which significantly reduces its fertility,leads to erosion of arable land, leaching of nutrients, andcarbon emissions . About 70 % of total greenhouse gas emissions account for the application and productionof nitrogen fertilizers, 10\u201315 % \u2013 for agrotechnical methodsof tillage, the rest \u2013 for the usage of pesticides and growthregulators .Annual crops occupy more than three quarters of the cropsarea in the world according to the latest data, so an importantelement of regenerative agriculture is creating a rationalstructure of cultivated areas and increasing the biodiversityof cultivated crops . In the comingdecades, the expansion of cultivated areas under perennialcrops, in addition to annual crops, will create opportunitiesfor transitioning agriculture to a more sustainable developmenttrajectory, reduce production costs, and improve theagrocenoses state .Perennial crops have a longer growing period, due to whichthe soil is covered with vegetation longer, provide carbonaccumulation in the soil, and reduce greenhouse gas emissions.They have increased resistance to many negative biotic andabiotic environmental factors, form a powerful root systemthat improves plant water consumption and reduce nutrientlosses in the soil . Thewheatgrass Thinopyrum intermedium (Host) Barkworth &D.R. Dewey and oilseed culture Silphium integrifolium Michx.are examples of successful domestication of perennial crops.Wide hybridization of annual crops with perennial wild relativesis carried out in many scientific institutions and universitiesaround the world to create such perennial crops as wheat,sorghum, rice, barley .Allohexaploid species Th. intermedium (2n = 6 x = 42)(= syn. Agropyron glaucum (Desf. ex DC.) Roem. & Schult.= Elytrigia intermedia (Host) Nevski) is a perennial wild speciescharacterized by a wide variety of morphological propertiesand high adaptability to biotic and abiotic stresses . This species is included in the tertiary genepool, differs from all other species of the genus ThinopyrumA. L\u00f6ve by high crossbreeding with bread wheat (averagegrain percentage of hybrids is 24) . However, the transfer of valuable genes from IWGto bread wheat is difficult, which is explained by limited recombinationbetween chromosomes of these species in distanthybrids. Four main methods are used for targeted introgressionsfrom the homeologous chromosomes of wild wheatrelatives to the wheat genome: spontaneous translocations,radiation exposure, tissue culture, and induced homeologousrecombination. The last method is used provided that the targetgene is removed from the near centromeric regions whererecombination is absent or difficult .The genomic composition of Th. intermedium (JJSSt)has been studied for decades. The results of genomic in situhybridization (GISH) with usage of labeled DNA of differentdiploid species as probes showed that the J-genome isrelated to the genome of diploid species Th. bessarabicumand Th. elongatum, and the JS-genome \u2013 modified form of thegenome Th. elongatum/Th. bessarabicum. The St-genome isthe main genome of perennial grasses; it shows great similaritywith the genome of genus Pseudoroegneria, which isthe most probable maternal parent of Th. intermedium .In the 1930s, scientists had great expectations for widehybridization, when N.V. Tsitsin in the Soviet Union, as wellas other scientists in the USA and Canada, began to developperennial wheat forms by crossing bread wheat with IWG. In the Main BotanicalGarden named after N.V. Tsitsin of the RAS (Moscow),under the leadership of academician N.V. Tsitsin was formeda unique collection, which included the octoploid forms ofwheat-wheatgrass hybrids (WWGHs) obtained using differentspecies of wheatgrass, as well as varieties Istra 1, Zernokormovaya169, Ostankino, Otrastayutshaya 38 . For the first time, the winter bread wheat varietiescharacterized by medium level of winter hardiness were createdon the basis of wheat-wheatgrass hybrids WWGH 599 andWWGH 186. In the 1970s, the variety Zarya was developedin the Federal Research Center \u201cNemchinovka\u201d, which wascultivated on an area larger than 500 thousand hectares . Modern varieties and lines Multi 6R, Lebedushka, Belyanka of Samara ARI have a substitutedchromosome 6D(6Agi); varieties Tulaykovskaya 5, 10, 100of Saratov ARI have a substituted chromosome 6D(6Agi2)with highly effective resistance genes to brown, stem, yellowrust, and powdery mildew belonging to Th. intermedium. In Western Siberia,some perspective WWGHs based on Th. intermedium andAg. \u0435longatum were developed. They are recommended forinclusion in hybridization with varieties of winter and springbread wheat in order to increase winter hardiness, resistanceto rust diseases, and grain quality . In China, since the early 1950s,systematic work has been carried out to increase wheatresistance to different abiotic and biotic environmental factorsusing Th. intermedium. The WWGHs with characteristicssuch as high winter hardiness, disease resistance, improvedfeed properties, and rapid post-harvest regrowth wereinvolved in the breeding of perennial fodder wheat .Biotechnological and molecular cytogenetic approaches totransfer the target gene to modern wheat varieties and reducethe unwanted alien chromatin of wild wheat relative are used. The genes of resistance to leaf, stem,yellow rust, powdery mildew , barley yellow dwarf virus , and wheatstriped mosaic (Wsm1) were transferred to the wheat genomefrom IWG .Molecular markers for the analysis of the Th. intermediumgenome, which makes it possible to purposefully transferwheatgrass genes into the wheat genome, were developed.In particular, molecular markers have been developed toidentify wheatgrass genes in the wheat genome: CAPS-markerfor the Vp-1 gene is used in breeding to increase resistance topre-harvest sprouting ; CAPS-marker P22F/PRa/PvuII for the DREB1gene, for the wheat drought tolerance breeding ; molecular and cytogenetic markers specific towheatgrass chromosome 1St#2, for breeding to increase theprotein and gluten content in wheat grain ; WXTH-marker for the Wx gene, for changing starchcomposition and technological properties ; PLUG, SCAR and Thi-GBS-markers, for identifyingthe chromosomes of the J-, JS-, and St-genomes of wheatgrass.Along with molecular markers, cytogenetic markers areeffectively used to identify chromosomes and their segmentsbelonging to Th. intermedium, which are associatedwith agronomic traits .The oligosondes (GAA)10, pSt122, pSc119.2-1, Oligo-B11,Oligo-pThp3.93, pAs1-1, pAs1-3, AFA-4 of the fluorescent(FISH) and genomic (GISH) hybridization are used tovisualize Th. intermedium chromosomes in WWGHs andintrogressive lines . Three cytogenetically markers of tandem repeats,which were specific to Th. intermedium chromatin on differentchromosomes of introgressive lines tolerant to phosphorusdeficiency were developed . Thepresence of reliable markers for wheatgrass chromosomesexpands experimental possibilities for using this cereal inwheat breeding.In 2016, the first consensus genetic map of IWG wasobtained. It consists of 10,029 markers, each of 21 linkagegroups contains between 237 and 683 markers with an averagedistance of 0.5 cM between each pair of markers . This map is of interest for identification of genesthat control economically important agronomic traits and theirintroduction into the wheat genome. A total of 111 QTLswere detected for 17 variable traits in the M26 \u00d7 M35 familyincluding several large-effect QTLs responsible for seedretention, plant height, seed weight, seed threshing, and othereconomically important agronomic traits. By the method ofassociation-mapping, 33 QTLs that control the grain sizeand weight were detected. When performing the selection offorms for seed weight, it was observed that the frequency offavorable QTL alleles in the IWG population was increasedto >46 % .Domestication of a new species is a risky and unpredictableprocess, because during selection for target traits, one cannotbe sure how other traits, desirable or undesirable for breeding,will change. In the 1980s, at the Rodale Research Center, IWG was selected for domestication andseed production from over 100 perennial species. Among perennialcrops, this cereal has relatively large seeds, moderatespike fragility, and good threshability, along with greater biomassand excellent quality of fodder . Two selection cycles according to agronomiccharacteristics and seed size were carried out. The perspectivegenets (clones) of wheatgrass were identified and transferredfor further study to the Land Institute .At the Land Institute, the selection cycles began with the developmentof indices based on the characteristics: seed weightper plant, seed weight per spike, percent of the bare seed,thousand kernel weight, and disease damage. A populationfor over-pollination was formed corresponding to the indicesin each selection cycle from 50\u201370 genets with the mostfavorable combination of traits. After two selection cycles,the grain yield per unit area increased by 77 %, and the seedweight, by 23 % . At the Land Instituteand the University of Minnesota , the resultsof genome sequencing were actively used for the domestication of Th. intermediumin order to replace time-consuming selection by phenotypeby GWAS and bioinformatics methods .As a result of many years of work at the Land Institute,the wheatgrass variety Kernza was developed (named afterthe residents of Kansas), used both for seed production,green mass, and hay (haylage). During the second year ofthe cultivating of the variety, there was an 86 % nitrate reduction in groundwater, and a 13 % increase in soil carbonsequestration compared to annual crops . Kernza is practically not affected by diseases andpests, the crop requires fewer agrotechnical operations, suchas nitrogen fertilizers, tillage, pre-sowing seed treatment, andfungicide protection, thereby reducing energy and economiccosts .During the cultivation period of Kernza in Kansas in2012\u20132016, the nitrogen fertilization has changed overtime, beginning with \u223c110 kg per ha in 2012 and graduallydecreasing to \u223c80 kg per ha in 2016. For this period, carbonemissions were reduced from 513 to 121 g C\u00b7m\u22122. Over thewhole study period, the total carbon fixed was \u223c50 % higherthan the carbon lost via respiration. Based on the cumulativenet ecosystem exchange data (NEE), it was found that theperennial wheatgrass represented a substantial carbon sink590.4 g C\u00b7m\u22122 per year .A five-year cultivation of the wheatgrass variety Kernza hadpositive effect on the soil structure and yield of the followingcrops in the crop rotation: it increased the microbiologicalactivity and soil microbiota diversity compared to the soilmicrobiota under maize harvested for silage . In comparison with annual crops such as maize andwheat, the variety \u041a\u0435rnza also had a higher ability of maintainingthe water-use efficiency (WUE) and evapotranspiration(ET) \u2013 about 97 % throughout the whole growing season.This was achieved thanks to a strong root system and wateruptake from deeper soil layers, which is an important mechanismof adaptation to water deficit conditions .In 2011, a joint breeding program for improvement ofKernza was launched between the Land Institute and theUniversity of Minnesota, which contributed to the commercialinterest emergence for this perennial cereal. It wasdeveloped as a synthetic population at the University ofMinnesota, prioritising grain-type direction, MN-Clearwater, which can be cultivatedfor biomass and forage. Among 2,560 IWG genets receivedfrom the Land Institute, seven parents were selected accordingto the following set of characteristics: days to heading, plantheight, spike weight, percentage free grain threshing, seedweight, and biomass weight to create a synthetic population ofMN-Clearwater. In variety trials across Minnesota, MNClearwaterproduced 696 kg \u00b7 ha\u22121, the thousand kernelweight was 6 g. This is a short-stemmed variety (113 cm),which had a good threshability (63 %), and low stem fragilitywith minimal lodging during research years . Programs for domestication and improvement ofsuch IWG traits as seed size, threshability, reduction of spikefragility, and plant height for increasing resistance to lodgingand diseases are also implemented at the University ofManitoba (Canada), at the University of Utah (USA), and atthe University of Agricultural Sciences .The introduction of optimal doses of fertilizers and appropriateagricultural technology increase the wheatgrass yield.Thus, in the autumn sowing of IWG population of grain-type(TLI-C2), grain yield was highest during the first year inresponse to nitrogen fertilization \u2013 961 kg \u00b7 ha\u22121 and graduallydecreased in subsequent production years . The experience of American farmers shows that IWGcan be cultivated without replanting for 4\u20136 years, making anet profit by reducing production costs. The area occupied byKernza in the USA in 2014 was approximately 87 hectaresand doubled to 170 hectares in 2016. For further growth ofthe areas occupied under this crop, information on optimalestablishment practices, assessment of forage nutritive value,ways to maintain grain yields over years, and weed managementis needed .An important aspect of the popularization of IWG in Americaand Europe was the use of Kernza grain for food production. Bakery products, crackers, cereals,snacks produced on the basis of wheatgrass grain have a sweetnutty taste. The companies General Mills and Patagonia Provisionsproduce the wheatgrass grain goods under the trademarkKernza\u00ae, which belongs to the Land Institute. Currently, thesecompanies are expanding the markets for these products.A chain of Birch Wood cafes has been opened in Minneapolis,serving tortillas and pancakes baked from flour of wheatgrassKernza .Studies have been conducted for evaluation of technologicalcharacteristics of wheatgrass grain. The results have been usedfor the development of food products. The IWG grain qualityis not inferior to wheat grain, but at the same time, there aresignificant differences .IWG is characterized by a high protein and fiber content inwhole grain flour \u2013 20 and 16.4 %, while in whole grain wheatflour their content is 13 and 11 %, respectively . Protein has more essential amino acids comparedto wheat, in particular, 1.4 times more cysteine and methionine. The results of a 3-year research onthe IWG variety Sova (Th. intermediate) under conditionsof the southern forest-steppe of Western Siberia showed thatthe protein content in grain varied from 18.5 to 20.5 %. Forthe third year of the variety\u2019s production, the protein contentincreased by 2 %. This is probably related to an increase inthe total number of important agronomic groups of microorganismsin the rhizosphere under the variety Sova, developmentof more powerful root system, and weather conditions.Wheatgrass glutenin proteins contain fewer high-molecularweightglutenin subunits (HMW-GS), which are similar instructure to wheat HMW-GS (67\u2013120 kDa), but have a lowerweight \u2013 45\u201390 kDa . The deficiencyin HMW-GS with a molecular weight of >60 kDa in wheatgrassgrain causes a weak gas-holding capacity and doughelasticity, which, in turn, leads to low bread making quality.Due to the small size of wheatgrass seeds, they containedsignificantly less starch (46.7 %) compared to wheat (72 %),as well as more albumin and globulin proteins in the aleurone layer. However, during domestication, the seed weightwas increased by 23 % , which led toan increase in the endosperm proportion in the seed and,accordingly, starch. The technological and digestive propertiesof starch depend on its content. The management ofits components, amylose and amylopectin can be regulatedusing combinations of alleles of Wx genes in Th. intermedium. In contrary to wheat starch,wheatgrass starch has a higher proportion of long amylosechains, a lower gelatinization temperature, which reducesthe starch viscosity and retrograde and makes it suitable forthe production of baked goods with a lower glycemic index. Th. intermedium grain can also be usedin a mixture with hard red wheat grain for the production ofbaked goods with a low glutenin content .Mixing wheatgrass grain flour and durum wheat grain flourin a ratio of 50:50 contributes to a good balance betweenthe functional characteristics and digestive properties ofbaked goods. Particularly, cookies made of wheatgrass grainflour had the same quality as cookies made of ordinary wheatflour. In addition, the increased content of dietary fibers andantioxidants in wheatgrass flour baked goods makes themespecially useful for human health .Omsk State Agrarian University initiated a study on thecultivation of perennial wheat samples obtained from the internationalCIMMYT collection and wheatgrass populationsdeveloped at the Land Institute. The city of Omsk becameone of the sites among multilocation experiments of perennialcrops germplasm, the results of which are presented inthe article of R.C. Hayes et al. (2018). The variety Sova wasdeveloped by mass selection of overwintered biotypes from theTh. intermedium population received from the Land Institute.Several selection rounds were carried out on the basis of traitsof winter hardiness and spike productivity. The productivitycomponents of 100 spikes were evaluated according to thefollowing characteristics: spike weight and length, the numberof spikelets and grains per spike, the number of grainsper spikelet, grain weight per spike. A synthetic populationadapted to the conditions of the southern forest-steppe ofWestern Siberia was formed by directed pollination of theselected biotypes. In 2020, the large-grain wheatgrass varietySova was included in the State Register of Breeding AchievementsAllowed for Use and recommended for cultivation inall regions of Russia .The variety Sova can be cultivated as a dual-use crop \u2013 forgrain and forage. The average grain yield was 0.92 t/ha, greenmass \u2013 21.0 t/ha, and hay \u2013 7.1 t/ha .Omsk State Agrarian University produces original seeds of thevariety Sova with subsequent reproduction of the elite categoryseeds in three basic farms of Omsk State Agrarian University:\u201cTriticum\u201d, \u201cNiva\u201d, and \u201cGovin\u201d. In 2020, about 5 seed tonsof the variety Sova were produced for farmers in the Omskregion. The average grain yield in the southern forest-steppeand steppe zones of the Omsk region was 0.4\u20130.6 t/ha.Despite some progress made in the implementation ofindividual breeding programs, there are many tasks that requirefurther selection solutions to improve the efficiency ofwheatgrass cultivation as a perennial grain crop. First of all,it is necessary to increase the yield of wheatgrass grain. Thegrain yield of wheatgrass is lower than that of spring wheat,because part of its energy is spent on the development ofthe root system and branching after overwintering. A furtherincrease in the wheatgrass grain yield can be achieved byrepeated selections of forms with a smaller plant length anda smaller number of grains per spike, which seems advisableto increase the thousand kernel weight (TKW). Thisis evidenced by the research results, in which a negativecorrelation between the TKW and the plant height , between the TKW and the number of grains perspike was noticed .The usage of genomic technologies and molecular mappingfor the selection of genotypes with valuable traits will greatlycontribute to improving the efficiency of breeding for increasingthe grain yield of this perennial crop.Efficient seed production technologies and agrotechnicalmethods of wheatgrass cultivation in specific agro-climaticzones are also a reserve for increasing the yield of this crop.For producing bread and bakery goods made of wheatgrassgrain with functional properties, it is necessary to developtechnologies for the food industry and market the demand for this product by the population, which will allow to forma stable demand for this crop on the market.The above review of world research shows that IWG is a culturewith great production potential, beneficial ecologicalproperties and valuable grain for functional food. Cultivationof Th. intermedium and other perennial crops \u2013 sorghum, rice,barley, Silfium, meadow and pasture grasses in agriculturewill provide not only ecological, but also social and economicbenefits. This is also important due to challenges associatedwith the climate warming, the necessity to reduce the greenhouseeffect, in agricultural production as well. The grain ofIWG can be used for bakery and confectionery products withimproved nutritional value, and the whole plant can be usedfor biomass, hay, and haylage. IWG has increased resistance tomany negative biotic and abiotic environmental factors, formsa strong root system that improves plant water consumption,reduces nutrient losses in the soil and carbon emissions. Thewheatgrass varieties Kernza and Sova developed at the LandInstitute (USA) and at Omsk State Agrarian University (Russia)indicate good prospects for breeding improvement of thiscrop. 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Cereal Chem. 2019;96(5):927-936. DOI 10.1002/cche.10196."} +{"text": "Thanerosus antiquus gen. and sp. nov. is described as the fourth Cretaceous representative of Thanerocleridae. The set of characters observed in the new species suggests its basal position within the family and its relationship with the ancestral North American Zenodosus sanguineus, the single extant member of the subfamily Zenodosinae. The observance of some characters, including the mouthparts and details on the thorax\u2019s ventral side, was only possible after the 3D reconstruction of the fossil following its X-ray micro-CT scanning. This fact reinforces the effectiveness of this non-destructive technique for evolutionary studies through the use of fossils. We speculate on a wide diversification and distribution of this predatory family originally connected with an ecological community of saproxylic insects in the Cretaceous that were followed by habitat change and specialization of life inside fruiting bodies of fungi. Consequently, the family has not been recorded from the Cenozoic fossil collections yet and currently shows limited diversification.The use of new technologies applied to paleontological studies offers more detailed and attractive results each time. We describe a new genus and species of the relative rare beetle family Thanerocleridae (Cleroidea). Thanerosus antiquus gen. and sp. nov. is based on one fossil specimen preserved in an amber piece from Upper Cretaceous Kachin amber. The holotype was imaged using an X-ray micro-CT system to obtain high-quality 3D images. A phylogenetic analysis based on 33 morphological characters supports the placement of the new genus at the basal position in a tree of Thanerocleridae, in the vicinity of extant Zenodosus Wolcott and three extinct Mesozoic genera with which the new fossil shares open procoxal and mesocoxal cavities and transverse procoxae. We offer here a key to all extant and extinct genera in the family together with a complete list of all valid thaneroclerid taxa.The predaceous beetle family Thanerocleridae is one of the smallest families of Cleroidea. It comprises only 36 extant species widespread on all continents. Three more species have been described from Cretaceous ambers of Myanmar and France. The fourth fossil representative of Thanerocleridae is described herein. Mathesius liaoningensis Kolib\u00e1\u010d and Huang (Cleroidea incertae sedis), was denoted a presumptive relative of the clerid or thaneroclerid branches of Cleroidea [Thanerocleridae is a small family of cleroid beetles comprising 36 living species in ten extant genera ,2,3,4 anleroidea . Still, Zenodosus Wolcott lives in the temperate zone. Only the cosmopolitan single species Thaneroclerus buquet Lefebvre is known in Europe [The family is distributed worldwide, mostly in tropical and subtropical climates although one monotypic genus n Europe . Howevern Europe . Some spn Europe .Thanerocleridae constitutes one of the smallest families of the superfamily Cleroidea. It was initially included as a subfamily in Cleridae until Kolib\u00e1\u010d elevatedZenodosus sanguineus (Say)) belong to the subfamily Thaneroclerinae [Z. sanguineus occurs in southeastern Canada and the eastern, central, and southern United States [Currently, Thanerocleridae comprises two extant subfamilies, Zenodosinae and Thaneroclerinae, the latter with two tribes, Isoclerini and Thaneroclerini ,11. All clerinae ,20,21,22clerinae ,6,7. TheThanerosus antiquus gen. and sp. nov. is a further new thaneroclerid beetle described within Zenodosinae. The new genus is substantially different from the rest of the fossil representatives of the subfamily, providing evidence of a wider morphological variation of the group and showing an already demonstrated distribution of the lineage in the Cretaceous. It is the fourth species of Thanerocleridae to be described from the Mesozoic ambers, the third one from the same deposit of Kachin (Myanmar). However, its observation using a micro-CT scan suggests that this fossil might be a relative of the single extant zenodosine member Zenodosus sanguineus from North America more than the other burmite species.This study is based on one fossil specimen found in a sample of Kachin amber (Myanmar). The amber from Myanmar, many times referred to as Burmese amber, has a long history of excavation. The active amber mines in Myanmar have increased in the last years ,24. ThisThe holotype denoted as NIGP180154 is included in a polished oval sample of amber along with one syninclusion of a Diptera specimen (probably Tipulidae). The sample was further ground and polished to better observe the characters of the specimens. It was examined under a Leica MZ95 stereomicroscope and a Leica DME compound microscope . Detailed photomicrographs of the fossil were created using an Olympus CX41 compound microscope and a Leica MS5 stereomicroscope , both equipped with a digital camera sCMEX-20 , under incident light and using the software ImageFocusAlpha version 1.3.7.12967.20180920 , finally merged with the software CombineZP.The holotype was imaged at the Nanjing Institute of Geology and Palaeontology (NIGP) with a Zeiss Xradia 520Versa X-ray micro-CT system to obtain high-quality 3D images. Considering the comparatively small size of the fossil, a CCD-based 4\u00d7 objective was used, providing isotropic voxel sizes of 2.3938 \u03bcm with the help of geometric magnification. Images were generated at an X-ray voltage of 50 kV. Four frames per projection were acquired with an integration time of 3.5 s for 2801 projections over 360\u00b0. Acquired images were rendered and visualized using Avizo 8.1 . Video presentations are included in The final images were edited with Adobe CS6. All relevant structures were measured from the digitized images. The specific terminology for characters follows that of Kolib\u00e1\u010d & Leschen . We follAcanthocnemus nigricans Hope (Acanthocnemidae), Tenebroides mauritanicus Linnaeus (Trogossitidae), Tilloidea transversalis Charpentier (Cleridae: Tillinae), and Clerus mutillarius Fabricius (Cleridae: Clerinae). Trees were rooted with Acanthocnemus nigricans, which was revealed as the basal taxon in the specialized molecular phylogeny of Cleroidea by Gimmel et al. [Mesozenodosus insularis Tihelka et al., 2020 and Cretozenodosus fossilis Cai & Huang, 2018; (2) with modified character state 7 (0) (mandible unidentate) and state unknown 7 (?), respectively. Parsimony analysis was conducted with implied weighting . Tree sOrder Coleoptera Linnaeus, 1758Suborder Polyphaga Emery, 1886Superfamily Cleroidea Latreille, 1802Family Thanerocleridae Chapin, 1924Subfamily Zenodosinae Kolib\u00e1\u010d, 1992Thanerosus gen. nov. Peris & Kolib\u00e1\u010dFigure 4Type species. Thanerosus antiquus gen. and sp. nov. here designated.Etymology. The generic name is derived from the prefix \u2018Thanero-\u2019 following the family name, and \u2018-sus\u2019, termination of the most basal extant representative of the family (Zenodosus Wolcott). It is masculine in gender. The genus is registered under Zoo-Bank LSID: 84DA2BE8-C471-44F9-A4AF-FEE0C6EE6F2E.Type, locality. Kachin State, near Tanai, northern Myanmar; Upper Cretaceous (lower Cenomanian) in age [) in age .Diagnosis. Dorsal surface with dense and elongate setae; terminal palpomere of maxillary palps coniform; labial palpi with three segments, terminal palpomere weakly securiform; 11-segmented antenna with loose but distinct 3-segmented club; anterior edge of clypeus straight, labrum distinctly emarginate medially; mandible unidentate, incisor edge with single blunt subapical teeth; prothorax with lateral carina visible along the whole length; procoxal cavities externally open, procoxae weakly transverse, pair of depressions along notosternal sutures present; scutellum quadrate; all tibiae with two spurs present at apex; tarsal formula 5-5-5, meso and metatarsomeres 2\u20134 with conspicuous lobes, empodium bisetose.Remarks. Thanerosus gen. nov. can be referred to Thanerocleridae based on the general body shape, head prognathous and its base as wide as pronotum; prothorax with complete lateral carina, the base of pronotum bordered; all coxae narrowly separated; metacoxae extending laterally to meet elytra, metanepisternum elongate; protarsomeres 1\u20134 wide with tarsi compact, tarsal claws simple; abdomen with five ventrites [entrites ,9,13. ThZenodosus and all three fossil thaneroclerids described to date are placed in Zenodosinae based on the procoxal cavities open and the procoxae transverse. By contrast, species in Thaneroclerinae possess the procoxal cavities externally closed and procoxae more or less spherical [Thanerosus gen. nov. also corresponds with zenodosines, whereas depressions along notosternal are known only in the tribe Isoclerini.The recent genus pherical . The shaThanerosus antiquus gen. and sp. nov. Peris & Kolib\u00e1\u010dFigure 4Holotype. Holotype NIGP180154, adult specimens, sex unknown. The type specimen is deposited in the Nanjing Institute of Geology and Palaeontology, Chinese Academy of Sciences, Nanjing, China. The holotype lost the apical section of the left antenna before being embedded in resin.Type locality. Kachin State, near Tanai, northern Myanmar; Upper Cretaceous (lower Cenomanian) in age [) in age .Etymology. The specific epithet is designated after the Latin antiquus, meaning old or ancient. It is masculine in gender. The species is registered under Zoo-Bank LSID: 13AB22E2-8519-4C5A-BF09-0926A7889884.Diagnosis. As for the genus.Description. Body length dorsally 2.24 mm; length of elytron 1.41 mm, the width of elytron at base 0.85 mm, a maximum width of pronotum 0.7 mm, length of pronotum 0.66 mm. Body 1.59 times as long as wide.Coloration and structure: body elongate and subcylindrical A; wingedHead: prognathous, as wide as prothorax, artificially declined in fossil; sharply incised epicranial acumination present A; frontoThorax: pronotum subquadrate, about as long as wide, convex, widest at one-third from the base and only very slightly narrowed towards base, lateral sides very weakly arcuate; pronotum without depressions or grooves, convex. Lateral pronotal carina complete; the base of the pronotum carinate E; anteriLegs: slender and long, setose. Trochanters triangular. Femora widest near middle, weakly grooved for the reception of tibiae. Tibiae is widest apically, each with two short apical spurs B,D. TarsAbdomen: five smooth ventrites present, without visible punctation and pubescence C; first Thanerosus antiquus gen. and sp. nov. are placed in Zenodosinae, as the other three fossil species of the family, based on the procoxal cavities open and procoxae transverse , scutellum transverse and broadly rounded apically, and elytral base about as broad as the base of pronotum [Thanerosus antiquus gen. and sp. nov. is much smaller in length, clothed dorsally with long setae, pronotum widest at one-third from its base, depression along notosternal suture present, procoxal cavity transverse, scutellum quadrate and apically arrowhead-shaped, and elytral base distinctly wider than the base of pronotum. Cretozenodosus fossilis Cai & Huang lacks depression along notosternal suture and base of pronotum half the width of elytral bases [Thanerosus antiquus gen. and sp. nov. Moreover, the description of Cretozenodosus mentions bidentate mandibles; however, this structure is not figured and is highly improbable in Thanerocleridae.Thanerocleridae had been originally classified within the Cleridae until Kolib\u00e1\u010d raised tansverse C. The neenodosus . Mesozench amber , has thea et al. the single most parsimonious tree A and (2)Zenodosus as the most ancestral member of the family. A proof supporting the idea of Zenodosinae as the basal thaneroclerid group is that all the fossils described in the family so far, always from Cretaceous ambers, are different genera of the same subfamily. All four fossil species possess ancestral characters such as externally open procoxal cavities (12-0) and transverse or oval procoxae (13-0).Sister relation of the family Thanerocleridae and Cleridae is well-supported in our analysis (Bremer support > 1), as similarly occurred in previous studies . Kolib\u00e1\u010dZenodosus and Thanerosus share the open mesocoxal cavities (14-0) (mesepimeron touches mesocoxa) while all other thaneroclerids but Ababa Casey (character unknown in Mesozenodosus) have the cavities closed by projections of meso- and metaventrite which character state is considered apomorphic (14-1). That is the reason for the sister relation between Zenodosus and Thanerosus shown in Cretozenodosus and Mesozenodosus (see above). No single taxon in the whole clerid lineage has the bidentate mandible with two apical teeth situated side by side as in other cleroids and the major part of cucujoid beetles. Moreover, as already noted above, the figure of the Mesozenodosus mandible shows the unidentate mandible [mandible .Ababa + (the tribe Isoclerini) is based on a flat eye not exceeding the contour of the head (4-0) and especially unique synapomorphy 18-1 . The clade comprising the five remaining extant genera Onerunka Kolib\u00e1\u010d + ) (the tribe Thaneroclerini) shares apomorphic irregular sculpture of elytron (23-1).The subfamily Thaneroclerinae is supported with three apomorphies: procoxal cavities externally closed (12-1/2), procoxa almost spherical (13-1), wing with radial cell absent (25-1). The clade Zenodosus sanguineus, the major part of extant thaneroclerids (the species-richest genera Isoclerus and Neoclerus) hunt for prey in a tree or freely growing fungi. Probably, the four extinct thaneroclerids, including Thanerosus antiquus gen. and sp. nov., found in European and Asian Cretaceous ambers, had the ancestral biological pattern connected with the ecological community of saproxylic insects, like many other groups of amber bearing beetles from the Cretaceous ambers [Zenodosus sanguineus.Up to now, Melyridae, Mauroniscidae, Prionoceridae, Lophocateridae, Trogossitidae and Cleridae are the six cleroid families found in the Middle Jurassic of northeastern China . Fossil s ambers . It is ps ambers . Althougs ambers ,19, as ss ambers , and preCleridopsis Champion (type of genus: C. latimanus Champion by monotypy) from Central America was described within Cryptophagidae [Cleridopsis with Thanerocleridae. Kolib\u00e1\u010d [C. latimanus specimens. A synonymization of Cleridopsis with Ababa from the same geographic region has been recently made by Opitz [Ababa and Parathaneroclerus, although the taxa are extremely similar and rather congeneric. Therefore, Cleridopsis is not included in the following key, and both latter taxa are treated as genera.Kolib\u00e1\u010d proposedphagidae by Opitz , who alsAllothaneroclerus Corporaal actually possesses the formula 5-4-4, not 5-5-5, as erroneously observed by Opitz [Isoclerus by Kolib\u00e1\u010d [Isoclerus tuberculatus Schenkling and the related I. succedaneus Melnik belong to Isoclerini and not to Thaneroclerini as suggested by Opitz [It should also be noted here that by Opitz . Moreove Kolib\u00e1\u010d . Therefoby Opitz (p. 16).1.Subfamily Zenodosinae.................................2Procoxal cavities externally widely open, procoxae oval or transverse; abdominal segment 9 fully developed; discriminal line present; tarsal formula 5-5-5; mesocoxal cavities externally open or closed. \u2013Ababa, Parathaneroclerus) closed; procoxa more or less spherical; abdominal segment 9 reduced to spicular fork (tergite and sternite VIII inconspicuous); discriminal line scarcely perceptible; tarsal formula 5-5-5 or 5-4-4; mesocoxal cavities externally closed, rarely open (Ababa). Subfamily Thaneroclerinae........................................................................6Procoxal cavities externally perfectly, rarely imperfectly ; elytron not depressed, without distinct humeral gibbae; abdominal ventrite 1 as long as 2 and 3 together, 2 to 5 subequal in length; winged species; southeastern and eastern Asia...........................................................................................................\u2013Viticlerus MiyatakeAntenna 11-segmented, club loose; elytron strongly depressed in anterior half, with elevated humeral gibbae; abdominal ventrite 1 as long as 2 to 4 together, 2 to 6 successively shorter; single wingless species; Fiji.....................11.Compactoclerus PicTendency to a coalescence of antennomeres 10 and 11 (suture between them perceptible), club 2-segmented; procoxae spherical, very small, space between them minute; prosternum in front of procoxa very long; terminal palpomere of labial palpi coniform; Africa, Madagascar.............................................\u201312Antennae 11-segmented with a more or less distinct 3-segmented club; terminal palpomere of labial palpi truncate; Americas, southeastern Asia........................12.Isoclerus LewisProcoxal cavities externally perfectly closed; southeastern Asia......\u201313Procoxal cavities externally imperfectly closed; Americas.................................13.Ababa CaseyMesocoxal cavities open; pronotum with weak depressions or flat; Americas......................................................................................................\u2013Parathaneroclerus PicMesocoxal cavities closed; pronotum with three conspicuous depressions; Brazil.........................................................................................................Subfamily Zenodosinae Kolib\u00e1\u010d, 1992Archaeozenodosus Yu & Kolib\u00e1\u010d, 2017 (type species: monotypic)Genus \u2020 bellus Yu & Kolib\u00e1\u010d, 2017\u00a0Burmese amber: Cenomanian\u2020 Cretozenodosus Cai & Huang, 2018 (type species: monotypic)Genus \u2020 fossilis Cai & Huang, 2018\u00a0Burmese amber: Cenomanian\u2020 Mesozenodosus Tihelka, Cheng, Huang, Perrichot & Cai, 2020 (type species: monotypic)Genus \u2020 insularis Tihelka, Cheng, Huang, Perrichot & Cai, 2020\u00a0Charentese amber: Cenomanian\u2020 Thanerosus gen. nov. Peris & Kolib\u00e1\u010d (type species: monotypic)Genus \u2020 antiquus sp. nov. Peris & Kolib\u00e1\u010d\u00a0Burmese amber: Cenomanian\u2020 Zenodosus Wolcott, 1910 (type species: monotypic)Genus sanguineus Say, 1835 (Clerus)\u00a0Canada, USASubfamily Thaneroclerinae Chapin, 1924Tribe Thaneroclerini Chapin, 1924Meprinogenus Kolib\u00e1\u010d, 1992 (type species: monotypic)Genus indicus Corporaal, 1939 (Cyrtinoclerus) India: Tamil NaduNeoclerus Lewis, 1892 Genus nanus Schenkling, 1901 (Thaneroclerus)\u00a0Indonesia: Java, Borneo, Sumatra; Malaysia: Malaccanilgiriensis Corporaal, 1939 India: Tamil Nadunotatus Pic, 1930\u00a0\u201cTonkin\u201d (North Vietnam/Laos)ornatulus Lewis, 1892 Japan, Taiwanquinquemaculatus Gorham, 1892 (Thaneroclerus)\u00a0MyanmarOnerunka Kolib\u00e1\u010d, 2012 (type species: monotypic)Genus longi Kolib\u00e1\u010d, 2012\u00a0Papua New GuineaThaneroclerus Lefebvre, 1838 Genus buquet Lefebvre, 1838 (Clerus)\u00a0cosmopolitan, origin probably in Indiaimpressus Pic, 1926\u00a0\u201cTonkin\u201d (North Vietnam/Laos)ishigakiensis Murakami, 2016\u00a0Japanquasitardatus Corporaal, 1939\u00a0India: Kashmirtermitincola Corporaal, 1939\u00a0Indonesia: SumatraViticlerus Miyatake, 1977 (type species: monotypic)Genus formicinus Miyatake, 1977\u00a0Fiji: Viti LevuTribe Isoclerini Kolib\u00e1\u010d, 1992Ababa Casey, 1897 Genus adona Opitz, 2018\u00a0Costa Rica, Panamaepiiska Opitz, 2018\u00a0Argentina, Bolivia, Perugranaria Opitz, 2018\u00a0Mexicolatimana Champion, 1913 (Cleridopsis) Guatemala, Panamatantilla Le Conte, 1865 (Clerus)\u00a0USA: Alabama, Illinois, Florida, Texas, Washington DC: Mexico; PanamaCompactoclerus Pic, 1939 Genus davidi Kolib\u00e1\u010d, 1992 Congorobustus Pic, 1939\u00a0Congosicardi Pic, 1939 (Microababa)\u00a0Madagascarzambiensis Kolib\u00e1\u010d, 1999\u00a0ZambiaIsoclerus Lewis, 1892 Genus cipisek Kolib\u00e1\u010d, 1998\u00a0Australia: New South Walesdisinlei Kolib\u00e1\u010d, 1992\u00a0Taiwanelongatus Schenkling, 1906 (Thaneroclerus)\u00a0China: Yunnangerstmeieri Kolib\u00e1\u010d, 1998\u00a0Australia: New South Wales, Queenslandmanka Kolib\u00e1\u010d, 1998\u00a0Australia: New South Walesmenieri Kolib\u00e1\u010d, 1992 Indonesia: Lombokparallelus Lewis, 1892 (Lyctosoma)\u00a0China: Sichuan; Japan; Indonesia: Java, Sumatra; Vietnampictus Lewis, 1892\u00a0Japanrumcajs Kolib\u00e1\u010d, 1998 Australia: Queenslandsarawacensis Corporaal, 1939 Malaysia: Sarawaksuccedaneus Melnik, 2005\u00a0India: Tamil Nadutuberculatus Schenkling, 1906 (Neoclerus)\u00a0Sri LankaParathaneroclerus Pic, 1936 (type species: monotypic)Genus triimpressus Pic, 1936 Brazil: Rio Grande do Sul"} +{"text": "Paracontrochuscapensis as a synonym of Monohedotrochuscapensis . P.capensis on Duncaniacapensis Gardiner, 1904. In other words, P.capensis and should be considered to occur in South Africa. Below we present the updated species synonymy and the revised figures.This is a short communication to revise the plates presented in the \ufeffText revisionMonohedotrochus Kitahara & Cairns, 2005Diagnosis. Corallum solitary, attached, straight, and elongate-conical to trochoid. Base monocyclic. Septotheca costate. Pedicel and base thick. Pali may be present, indistinguishable from columella. Columella papillose.Type species.Monohedotrochuscapitolii Kitahara & Cairns, 2005, by original designation.Monohedotrochuscapensis , comb. nov.Fig. 4I\u2013KCaryophylliacapensisDesmophyllumcristagalli. \u2013 Balanophylliacapensis. \u2013"} +{"text": "Following three courses of chemotherapy, he received cord blood transplantation (CBT) in the first complete remission. The patient developed mild skin acute graft\u2010versus\u2010host disease after CBT. In addition, he developed organizing pneumonia 1 month after CBT, which responded to steroid therapy, but repeatedly relapsed during steroid tapering. Thus, he had been receiving prolonged immunosuppressive therapy. Thirteen months after CBT, bluish\u2010red elevated lesions developed on the hard palate of the oral cavity Figure\u00a0. Biopsy The authors declare no conflict of interest.N.I., M.A., A.I., M.M, H.N., and H.I. were involved in the management of the patient. N.I., H.N., and H.I. wrote the manuscript. N.I., M.A., and A.I. prepared the figure. All authors reviewed and approved the manuscript.Informed consent was obtained from the patient."} +{"text": "Begonia has not only been recognised to be one of the mega-diverse plant genera but also as one found to comprise many undiscovered species. In particular, the increase of extensive field surveys in tropical regions of Southeast Asia has added to the discovery of many new species that are often found only in a few localities. In this study, the new taxon Begoniafimbristipulasubsp.siamensissubsp. nov. from Thailand is described. The Thailand accessions are highly similar in their morphology to accessions of B.fimbristipula from southern China but differ in their tuber shape, peduncle trichomes, petiole trichomes and number of female tepals. The new taxon has been found only in the northern parts of Thailand occurring at elevations above 1,300 meters. The new findings not only contribute to our knowledge of the plant diversity of Thailand but provide also critical information contributing to the protection of this species. In China, this species is endangered which is of special concern given its utilisation as a medical herb in traditional Chinese medicine. Considering IUCN Red List Categories, the new subspecies is considered to be Vulnerable. The disjunct distribution of the two subspecies of B.fimbristipula encourages urgently needed comparative taxonomic studies across the Indo-Burma biodiversity hotspot.The genus Begonia L. is an outstanding example of a mega-diverse plant genus A.DC. A.DC. . This se.) A.DC. . This ex.) A.DC. . As a coaryandra . 19 out oclinium . These poclinium . BesidesBKF) and Queen Sirikit Botanic Garden Herbarium at Chiang Mai (QBG) besides several prominent international herbaria . Distribution maps were generated using QGIS software (IUCN) Red List status was evaluated using information from field observation and the available specimen records.New accessions were examined and photographed in their natural habitats during field surveys in northern and north-eastern Thailand. They were consequently carefully compared to previously described species and as far as possible voucher specimens either by access to the voucher itself or to images. Special attention was given to type vouchers. To avoid describing an already published species, extensive comparisons were carried out with known species that showed high similarity in our first round of examination. The newly obtained voucher specimens were deposited at the two key herbaria in Thailand namely Forest Herbarium at Bangkok .Thailand \u2022 Phitsanulok Province, Nakornthai, Phu Hin Rong Kla national park, Lan Hin Pum rout; 1300 m a.s.l.; 29 Oct. 2001; S. Watthana, P. Suksathan 1570; herb on sand stone rather shed and wet; has been estimated as 32 km2 (http://geocat.kew.org/). Based on IUCN criteria, the status assigned is \u201cVulnerable\u201d ; C2 ) ) .Thailand \u2013 Chiang Mai Prov. \u2022 Pang Hin Fon, Mae Chaem District; 1300 m a.s.l.; 09 June 2017; W. Pongamornkul 6422; herb 20 cm high in dry evergreen forest, flowers pink; QBG 105946 \u2022 Dong Yen, Doi Chiang Dao; 1900 m a.s.l.; 20 Nov. 1999; P. Suksathan 2134; on mossy rock in shade; QBG16461. \u2013 Phitsanulok Prov. \u2022 Phu Hin Rong Kla national park; 1300\u20131600 m a.s.l.; 22 Jan. 2005; O. Kudjabnak, D. Watanachaiyingcharoen BRT (NU) 0046; herb on sand-stone; BKF SN152894. \u2013 Nan Prov. \u2022 Doi Phu Kha National Park, hill evergreen forest; 19\u00b013'N, 101\u00b006'E; 1750 m a.s.l.; 26 July 1999; P. Srisanga 918; herb on rock, leaves dark greenish-red, flower pink, stamen and stigma yellow; QBG15203 \u2022 ibid, Pua; 19\u00b010'N, 101\u00b007'E; 1800 m a.s.l.; 31 Aug. 2000; P. Srisanga 1533; hill evergreen forest, herb on rock, leaves greenish red, stem and pedicel red; QBG17980; BKF SN193126 \u2022 ibid, trail from Lan Doo Dao Phatang; 1700 m a.s.l.; 26 June 2008; R. Pooma, M. Tamura 7104; on moist rock surfaces, densely mosses, lower montane forest; BKF SN188535 \u2022 Doi Pha Phung, Nam Tok, Na Noi District; 18\u00b024'22.06\"N, 100\u00b032'50.24\"E; 992 m a.s.l.; 18 December 2018; P. Phaosrichai, M. Wongnak, S. Wongwan, S. Sitthisuk 1265; herb about 20 cm high, fruit brownish-red; QBG112488.China \u2013 Fujian Prov. \u2022 Wuyishan, on the way from ticketing entrance to Tienyoufeng; 270 m a.s.l.; 30 May 1997; Ching-I Peng 16885; HAST132046. \u2013 Guangdong Prov. \u2022 Ding-hu Shan; 06 May 1882; C. Ford 6; isolectotype K K000251078 \u2022 ibid; 150 m a.s.l.; 15 Apr. 1964; K.C. Ting, K.L. Shi 1402; BKF SN006485 \u2022 ibid; 6 May 1928; W.Y. Chun 6393; E E00299226 \u2022 ibid, Qingyuan Shi, Liannan Xian, Dalongshan Forest Plantation; 310 m a.s.l.; 4 Apr. 2005; Ching-I Peng 19496; on mossy rocky slope; HAST122379 \u2022 ibid; 26 May 1918; C.O. Levine 2027; E E00299227 \u2022 South of Ping Yung; 60\u2013175 m a.s.l.; June 1924; R.C. Ching 2002; P P06844316. \u2013 Guangxi Prov. \u2022 Zhuangzu Zizhiqu, Laibin Shi, Jinxiou Yiaozu Zizhixian, Dayiaoshan national nature reserve; 1200 m a.s.l.; 18 September 2003; Wai-Chao Leong 3673; on mossy rock face, mixed Cathaya and broadleaf forest; HAST 97112.Begoniafimbristipulasubsp.siamensis supports our expectation that several begonia species occurring in Thailand are still awaiting discovery. Our results are consistent with the accumulation of new species reported in recent studies, such as B.exposita Phutthai & M.Hughes, B.fulgurata C.I Peng, C.W.Lin & Phutthai, B.pengchingii Phutthai & M.Hughes, B.pseudosubperfoliata Phutthai & M.Hughes, B.phutthaii M.Hughes, B.sirindhorniana Phutthai, Thananth., Srisom & Suddee, B.tenasserimensis Phutthai & M.Hughes . We treat the newly found taxon as subspecies B.fimbristipulasubsp.siamensis because of the distinct morphological affinity to B.fimbristipulasubsp.fimbristipula. A comparison between these two taxa and a third similar species, namely B.poilanei Kiew . Thus, they are geographically disjunct taxa but future studies need to confirm the absence of occurrences bridging the gap in eastern Myanmar, northern Laos and northern Vietnam. In this context, it is worth noting that several putative relatives based on shared morphological similarities are known to occur in this region including B.poilanei from China and Vietnam (Begoniamengdongensis H.H.Xi from southeastern Yunnan, China (B.fimbristipula, whose plants are used to brew herbaceous teas, and as herbal medicine (The new finding of M.Hughes , 2021. Inei Kiew , was ass Vietnam and Begon, China . Currentmedicine ."} +{"text": "This paper reports on two new species and two new records of the lichen-forming fungal genus Peltula Nyl., highlighting progress in our investigation of Chinese Peltula spp. The external morphology, anatomy, and molecular systematics were comprehensively analyzed to support the species delimitation. The results contribute to the knowledge of species diversity and geographical distributions of Peltula species in China.Peltula confusa Q.X. Yang & X.L. Wei, sp. nov., growing in a dry microenvironment within a semi-humid area, and Peltula subpatellata Q.X. Yang & X.L. Wei, sp. nov., occurring in arid and semi-arid regions, are described. In addition, two species, P. polyspora (Tuck.) Wetmore and P. obscuratula (Nyl.) Poelt ex Egea, are recorded for the first time in China. All four species are described based on morphological, anatomical and molecular data. Peltula confusa is characterized by a lighter, brighter, and more yellowish upper surface than other species of this genus, with discs concentrated in the central part of squamules, and a thick lower cortex. Peltula subpatellata can be distinguished from P. patellata (Bagl.) Swinscow & Krog by its non-thickened and sometimes darkened margins and sometimes the presence of peltate squamules. Phylogenetic analysis based on DNA sequences of four loci demonstrates the placement of these species within Peltula, and supports current species delimitations. We suggest that the growth substrate should be considered as an additional characteristic for species delimitation.In this study, two new species, Peltula has grown to comprise more than 60 species since the type species, Peltula radicata Nyl., was described by Nylander in 1853. After being established, this genus name was not used further for a long period of time and many species that are now accommodated in the genus Peltula were described as part of the genus Heppia Naeg. It was not until 1935 that Peltula was mentioned again and began to be used as a separate genus . 1: 115 (1882). Type: Not seen.Basionym: Specimens examined: CHINA, Gansu, Baiyin City, Jingtai Town, Cuiliugou, 37\u00b024\u203251\u2033 N, 104\u00b035\u20324\u2033 E, alt 1640 m, on sandy soil, 18 Jan 2019, X.L. Wei et al. 20190012 (HMAS-L 154721); 37\u00b023\u203240\u2033 N, 104\u00b035\u203254\u2033 E, alt 1610 m, on sandy soil, 22 Apr 2019, X.M. Cheng & Q.X. Yang 20191252 (HMAS-L 154724); Ningxia, Zhongning County, Shangliushui Village, Qingshangen, 37\u00b04\u203216\u2033 N, 105\u00b023\u203213\u2033 E, alt 1738 m, on sandy soil, 19 Jan 2019, X.L. Wei et al. 20190162 (HMAS\u2013L 154722), 20190196 (HMAS\u2013L 154723).Thallus squamulose, terricolous; squamules round to sometimes slightly lobed, up to 2.5 mm, flat; margins usually darker; upper surface tan-olive, matte and sometimes cracked; attached to the substrate by a tuft of hyphae; isidia and soredia absent. Apothecia one to numerous per squamule, immersed; disc reddish black; epihymenium yellowish brown, K+ red-violet; hymenium 95\u2013180 \u03bcm; asci 90\u2013122 \u00d7 20\u201331 \u03bcm, bitunicate, an outer-wall-like gelatinous sheath present; ascospores globose, 4\u20136 \u03bcm. Pycnidia not seen.Peltula polyspora is new to China. It has previously been suggested as synonymous with P. patellata [P. polyspora and P. patellata are distinctly different. Therefore, our results support P. polyspora as a separate species. In P. polyspora clusters closer to P. subpatellata than to P. patellata. Tuckerman mentioned that Peltula polyspora has numerous apothecia [atellata ; howeverpothecia ; then, Wpothecia . Most ofpothecia . This sppothecia .Peltula are clearly revealed. In particular, in species with unclear morphological boundaries, DNA sequences could resolve their phylogenetic relationships. The specimens of Peltula subpatellata were preliminarily identified as P. patellata, but the phylogenetic analysis and further morphological comparison with Jason Hollinger\u2019s specimen (J. Hollinger 9078) revealed that these specimens represent a new species, different from P. patellata. Previously, there have been several reports of P. patellata, but in the absence of DNA sequence analysis, identification of these specimens was mainly based on their morphology alone. For example, Upreti & Budel described P. patellata from India as having a K- epithecium and noted that this species was similar to P. obscurans [P. patellata has a K+ epithecium and it is not similar to P. obscurans. To reach a more natural taxonomy and species delimitation it is essential that molecular data supplement morphological observations.In the four-locus phylogenetic analysis, the distance and genetic relationships among species of bscurans . In factPeltula confusa Q.X. Yang & X.L. Wei, sp. nov. and P. subpatellata Q.X. Yang & X.L. Wei, sp. nov., from Beijing and the northwest regions of China. These new species are rock-inhabiting in dry microenvironments within semi-humid regions, and soil-inhabiting in arid and semi-arid regions, respectively. In general, there is a trend in the substrate choice of Peltula spp. corresponding to the climate. Soil-inhabiting species, e.g., Peltula impressula, P. radicata, P. richardsii, and P. polyspora are distributed in (semi) arid regions, especially in the desert; the rock-inhabiting species, such as P. bolanderi, P. euploca, P. omphaliza, P. placodizans, P. polycarpa, P. sonorensis, P. submarginata, and most subfruticose species, need a dry microenvironment, but also require high levels of precipitation and light [Peltula.In this study, we described two new species, nd light ,33,34,36"} +{"text": "Conclusion, Paragraph 2. In the final sentence \u201crelationship\u201d should have read \u201crelationships.\u201d The corrected paragraph appears below.In the published article, there was an error in the \u201cThe present study identified male and female sources of belonging uncertainty in the computer sciences and thereby extends our understanding of this theoretical concept. Our results suggest that belonging uncertainty is comprised of both students' concerns about their social connectedness in an academic domain and concerns about their academic abilities. Therefore, conceptualizing belonging uncertainty as regarding only concerns about the quality of one's social relationships in an academic domain leads to an incomplete picture of this phenomenon.\u201dIn addition, there were also errors in some of the references in the published article.Am. J. Epidemiol. 109, 186\u2013204. doi: 10.1017/CBO9780511759048\u201d It should be \u201cBerkman, L. F., and Syme, S. L. (1979). Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda county residents. Am. J. Epidemiol. 109, 186\u2013204. doi: 10.1093/oxfordjournals.aje.a112674\u201d.The reference for Berkman and Syme (1979) was written as \u201cBerkman, L. F., and Syme, L. (1979). Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda county residents. Statistical Power Analysis for the Behavioral Sciences, 2nd Edn. Hillsdale, NJ: Lawrence Erlbaum Associated, Inc.\u201d It should be \u201cCohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, 2nd Edn. Hillsdale, NJ: Lawrence Erlbaum Associates, Inc.\u201dThe reference for Cohen (1988) was written as: \u201cCohen, J. E. (1988). Int. J. Public Health 58, 637\u2013643. doi: 10.1007/s00038-012-0416-3\u201d It should be \u201cEisinga, R., te Grotenhuis, M., and Pelzer, B. (2013). The reliability of a two-item scale: Pearson, Cronbach, or Spearman-Brown? Int. J. Public Health 58, 637\u2013642. doi: 10.1007/s00038-012-0416-3\u201d.The reference for Eisinga et al. (2013) was written as \u201cEisinga, R., te Grotenhuis, M., and Pelzer, B. (2013). The reliability of a two-item scale: Pearson, Cronbach, or Spearman-Brown? Pers. Soc. Psychol. Bull. 34, 542\u2013552. doi: 10.1177/0146167207312313\u201d It should be \u201cMarsh, H. W., and O'Mara, A. (2008). Reciprocal effects between academic self-concept, self-esteem, achievement, and attainment over seven adolescent years: unidimensional and multidimensional perspectives of self-concept. Pers. Soc. Psychol. Bull. 34, 542\u2013552. doi: 10.1177/0146167207312313\u201d.The reference for Marsh and O'Mara (2008) was incorrectly written as \u201cMarsh, H. W., and O'Mara, A. (2006). Reciprocal effects between academic self-concept, self-esteem, achievement, and attainment over seven adolescent years: unidimensional and multidimensional perceptions of self-concept. J. Educ. Psychol. 111, 331\u2013353. doi: 10.1037/edu0000281\u201d It should be \u201cMarsh, H. W., Pekrun, R., Parker, P. D., Murayama, K., Guo, J., Dicke, T., et al. (2019). The murky distinction between self-concept and self-efficacy: beware of lurking jingle-jangle fallacies. J. Educ. Psychol. 111, 331\u2013353. doi: 10.1037/edu0000281\u201d.The reference for Marsh et al. (2019) was incorrectly written as \u201cMarsh, H. W., Pekrun, R., Parker, P. D., Murayama, K., Guo, J., Dicke, T., et al. (2018). The murky distinction between self-concept and self-efficacy: beware of lurking jingle-jangle fallacies. J. Educ. Psychol. 108, 424\u2013437. doi: 10.1037/edu0000061\u201d It should be \u201cMaster, A., Cheryan, S., and Meltzoff, A. N. (2016). Computing whether she belongs: stereotypes undermine girls' interest and sense of belonging in computer science. J. Educ. Psychol. 108, 424\u2013437. doi: 10.1037/edu0000061\u201d.The reference for Master et al. (2016) was incorrectly written as \u201cMaster, A., Cheryan, A., and Meltzoff, A. N. (2016). Computing whether she belongs: stereotypes undermine girls' interest and sense of belonging in computer science. Stereotype Threat: Theory, Process, Application, eds M. Inzlicht and T. Schmader , 17\u201333.\u201d It should be \u201cMurphy, M. C., and Taylor, V. J. (2012). \u201cThe role of situational cues in signaling and maintaining stereotype threat,\u201d in Stereotype Threat: Theory, Process, and Application, eds M. Inzlicht and T. Schmader , 17\u201333.\u201dThe reference for Murphy and Taylor (2012) was incorrectly written as \u201cMurphy, M. C., and Taylor, V. J. (2012). \u201cThe role of situational cues in signaling and maintaining stereotype threat,\u201d in Psychol. Bull. 130, 261\u2013288. doi: 10.1037/0033-2909.130.2.261\u201d It should be \u201cRobbins, S. B., Lauver, K., Le, H., Davis, D., Langley, R., and Carlstrom, A. (2004). Do psychosocial and study skill factors predict college outcomes? A meta-analysis. Psychol. Bull. 130, 261\u2013288. doi: 10.1037/0033-2909.130.2.261\u201d.The reference for Robbins et al. (2004) was incorrectly written as \u201cRobbins, S. B., Lauver, K., Le, H., Davis, D., and Langley, R. (2004). Do psychosocial and study skill factors predict college outcomes? A meta-analysis. Psychometrika 74, 107\u2013120. doi: 10.1007/s11336-008-9101-0\u201d It should be \u201cSijtsma, K. (2009). On the use, the misuse, and the very limited usefulness of Cronbach's alpha. Psychometrika 74, 107\u2013120. doi: 10.1007/s11336-008-9101-0\u201d.The reference for Sijtsma (2009) was incorrectly written as \u201cSijtsma, K. (2009). On the use, misuse, and the very limited usefulness of Cronbach's alpha. Handbook of Research Methods in Personality Psychology, eds R. W. Robins, R. C. Fraley, and R. F. Kruger , 240\u2013258.\u201d It should be \u201cSimms, L. J., and Watson, D. (2007). \u201cThe construct validation approach to personality scale construction,\u201d in Handbook of Research Methods in Personality Psychology, eds R. W. Robins, R. C. Fraley, and R. F. Krueger , 240\u2013258.\u201dThe reference for Simms and Watson (2007) was incorrectly written as \u201cSimms, L. J., and Watson, D. (2007). \u201cThe construct validation approach to personality scale construction,\u201d in Psychology of Intergroup Relations, eds S. Worchel and L. W. Austin , 7\u201324.\u201d It should be \u201cTajfel, H., and Turner, J. C. (1986). \u201cThe social identity theory of intergroup behavior,\u201d in Psychology of Intergroup Relations, eds S. Worchel and W. G. Austin , 7\u201324.\u201dThe reference for Tajfel and Turner (1986) was incorrectly written as \u201cTajfel, H., and Turner, J. C. (1986). \u201cThe social identity theory of intergroup behavior,\u201d in Educ. Res. Eval. 3, 101\u2013118. doi: 10.1080/1380361970030201\u201d It should be \u201cTymms, P., Merrell, C., and Henderson, B. (1997). The first year at school: a quantitative investigation of the attainment and progress of pupils. Educ. Res. Eval. 3, 101\u2013118. doi: 10.1080/1380361970030201\u201d.The reference for Tymms et al. (1997) was incorrectly written as \u201cTymms, P., Merrell, C., and Henderson, B. (1997). The first at school: a quantitative investigation of the attainment and progress of pupils. Stereotype Threat: Theory, Process, Application, eds M. Inzlicht and T. Schmader , 89\u2013106.\u201d It should be \u201cWalton, G. M., and Carr, P. B. (2012). \u201cSocial belonging and the motivation and intellectual achievement of negatively stereotyped students,\u201d in Stereotype Threat: Theory, Process, and Application, eds M. Inzlicht and T. Schmader , 89\u2013106.\u201dThe reference for Walton and Carr (2012) was incorrectly written as \u201cWalton, G. M., and Carr, P. B. (2012). \u201cSocial belonging and the motivation and intellectual achievement of negatively stereotyped students,\u201d in J. Pers. Soc. Psychol. 103, 635\u2013646. doi: 10.1037/a0029120\u201d It should be \u201cWoodcock, A., Hernandez, P. R., Estrada, M., and Schultz, P. W. (2012). The consequences of chronic stereotype threat: domain disidentification and abandonment. J. Pers. Soc. Psychol. 103, 635\u2013646. doi: 10.1037/a0029120\u201d.The reference for Woodcock et al. (2012) was incorrectly written as \u201cWoodcock, A., Hernandez, P. R., Estrada, M., and Schultz, P. W. (2013). The consequences of chronic stereotype threat: domain disidentification and abandonment. Finally, an amendment has been made to footnote 4 in the original article. The first sentence previously stated: \u201cWe expected the relevant reference group for participants to be students in their tutorial group, rather all students in their study program, because we conducted our study in the tutorial classes of the first-year students.\u201d This should be: \u201cWe expected the relevant reference group for participants to be students in their tutorial group, rather than all students in their study program, because we conducted our study in the tutorial classes of the first-year students.\u201d The corrected footnote is found below:We expected the relevant reference group for participants to be students in their tutorial group, rather than all students in their study program, because we conducted our study in the tutorial classes of the first-year students. Hence, we expected students to be not yet familiar with many of their fellow students. In contrast to the teacher-centered teaching in lectures, students have to actively take part in the smaller and compulsory tutorial classes, e.g., by handing in weekly exercises that they worked on in groups, thereby getting to know each other faster. We therefore expected students to assess e.g., their performance potential and their affective as well as academic exclusion in relation to the students in their tutorial group.The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Soil microbial communities play a key role in the evolution of the rhizosphere. In addition, proper exploration of these microbial resources represents a promising strategy that guarantees the health and sustainability of all ecosystems connected to the ground. Under the inf luence of environmental conditions, microbial communities can change compositions in terms of abundance and diversity. Beyond the descriptive level, the current orientation of microbial ecology is to link these structures to the functioning of ecosystems; specif ically, to understand the effect of environmental factors on the functional structure of microbial communities in ecosystems. This review focuses on the main interactions between the indigenous soil microf lora and the major constituents of the rhizosphere to understand, on the one hand, how microbial biodiversity can improve plant growth and maintain homeostasis of the rhizospheric ecosystem, on the other hand, how the maintenance and enrichment of plant biodiversity can contribute to the conservation of soil microbial diversity; knowing that these microorganisms are also controlled by the abiotic properties of the soil. Overall, understanding the dynamics of the rhizosphere microbiome is essential for developing innovative strategies in the f ield of protecting and maintaining the proper functioning of the soil ecosystem The rhizosphere, a narrow area of soil that surrounds the rootsof plants, harbors a number of microorganisms that interactwith plants and the surrounding soil, and is considered one ofthe most dynamic interfaces on Earth . In addition, since their colonizationof terrestrial environments, terrestrial plants haveformed symbioses with microorganisms . They have been accompanied by fungi, bacteria, virusesand protists over millions of years, and those associations thatallow and accelerate the adaptation of plants to life on Earth.It has been estimated that the symbiosis between plants andfungi was established early with arbuscular mycorrhizal fungimore than 450 million years ago (Ma) during the colonizationof the Earth by plants, as the oldest and the most commonsymbiotic association of plants with microbes . However, the structure and activity of soil microbialcommunities are intimately linked to their roles in ecologicalprocesses; the identity and abundance of species presentin an ecosystem determine the types of interactions in therhizosphere and subsequently constitute the key elementsof the ecological theories . In addition,the soil microbiome is divided into two distinct microbialcompartments, depending on their position in relation to theroots of plants, the microorganisms surrounding the rootsbeing commonly referred to as rhizospheric or endophytes.Interactions between the plant and its microbiota range fromparasitism to mutualism, and their results can be decisive forthe performance of the plant . Endophytic soil microorganisms colonizeplant roots forming complex communities and perform beneficialfunctions by improving plant growth, health and defenseagainst enemies. This association improves the adaptation ofplants to environmental constraints such as drought and nutrientdeficiency . Thisbeneficial effect of the root microbiota on plants is achievedby the secretion of different growth hormones such as auxin,cytokinin and gibberellic acid, or by reducing the productionof ethylene. This leads to the promotion of plant growth bychanging the architecture of the root system and also by increasing theacquisition of nutrients .Thus, the plant microbiota can be considered as an extensionof the plant, in the sense that it can increase the plant\u2019s accessto nutrients in poor soils . Ithas been estimated that 80 % of vascular plant species receivephosphorus (P) and other nutrients from fungi in exchangefor photosynthesis . Inother words, microbial biodiversity is essential to enhance thesustainable growth of plants through improved nutrition, rootarchitecture, defense mechanisms and the competition withpathogens as well as through participation in the adaptationof plants to abiotic constraints.Bacteria are the most diverse organisms among living things. Their activity, richness and compositionplay a major role in the functioning of an ecosystem, eitherfree-living or associated with other host organisms .Microbial biodiversity studies use several methods dependingon the objective. Species diversity is the most studiedconcept despite it being a single dimension of biodiversity. This is due to the fact that species is thebasic unit of ecology and the evolution of ecosystems, hencethe importance of this concept for evaluating and conservingbiodiversity. However, definitions and formulas havebeen developed to fully understand and control microbialcommunities . These notions includethe measurement of biodiversity at spatial scales; accordingto Whittaker (1972), this notion is based on three scopes:(i) alpha diversity refers to the diversity within a particularecosystem (number or relative abundance of taxa); (ii) betadiversity expresses the total number of species unique to eachof the ecosystems compared; it makes it possible to examinethe evolution of the diversity of species between several ecosystems;(iii) the total or gamma diversity of a landscape, orgeographical area, is the product of the alpha diversity of itscommunities and the degree of beta differentiation betweenthem. Among these three parameters, alpha diversity is thekey element in conservation work because it quantifies thebiodiversity of a particular ecosystem through measurement based on the notion of presence/absence and abundance oftaxa within a local community.Despite the diversification of these mathematical tools, theyfail to reflect the added value of diversity within the ecologicalwhole. In this regard, the notion of functional diversityversus specific diversity appeared .This functional diversity is based on a metric for quantifyingthe diversity of functional traits . This callsinto question the philosophy of conservation biology, whichrecognizes that the great diversity of species ensures greatfunctional diversity and maintains the functional stability ofthe ecosystem .Soil microbial communities are vital for an ecosystem tomaintain the sustainability of long-term ecological interactions. They are essential to the plant due to theircontribution to its growth, its development and its productivity through the maintenance of soil fertilitythanks to the important roles they play in the availability ofnutrients . Soil microbial communitiesalso play a fundamental role in soil biogeochemical cycles because the dynamic structure of soillargely depends on the interaction between microbial biologyand the roots of plants living in the soil .However, there are a variety of factors that can significantlyaffect soil microbial communities and predict the abundanceand diversity of these communities. Among these factors,there are biotic factors such as root respiration and the natureof forest formation ;and abiotic factors such as temperature, climate, soil pH,moisture, organic matter also including nutritive elementssuch as nitrogen and phosphorus . These biotic and abioticfactors are very dynamic and consist of many elements thatcan interact and influence microbial communities in the soil.Some studies have elucidated that the interaction betweenmicrobial communities and soil biotic and abiotic factorsfunctions as an integrated impact of climate-soil-plant factorson the soil microbiome . More so, soil microbial communities react primarilyin response to changes in plant-soil interactions . Therefore, these microbial communities are essentialin order to maintain homeostasis of the entire rhizosphericecosystem .Afforestation has a very important role in the functioningof rhizospheric ecosystems, it improves soil conditions andpromotes soil development, especially in degraded ecosystemswith an extremely poor environment . In addition, soil microbes react quicklyto afforestation, which causes a huge increase in microbialproliferation . Dominant bacterialphyla, both Proteobacteria, Bacteroidetes, have been shownto be significantly more abundant in woodland than in abandonedland . In addition, thedevelopment of fungal communities also shows a significantincrease after afforestation in response to the improvement of the chemicalproperties of the soil as in the case of the conversion ofabandoned land into forest .However, natural forest ecosystems maintain greater soilmicrobial diversity than monoculture afforestation . Some studies have shown that Ascomycota respondedpositively to land use change while Basidiomycotaresponded negatively . Also, ecosystems thatcontain a mixture of different plant genera have the potentialto exhibit greater microbial community heterogeneity thansingle species plantations . From thisproposition, it can be concluded that changes due to afforestationtype may be related mainly to fungal phyla. Finally, thisshows that maintaining the variability of plant species duringafforestation greatly contributes to the conservation of themicrobial diversity of the soil.The effect of afforestation on microbial communities may bedue to the nature and diversity of plant species. In addition,plant species have been shown to significantly influence thecomposition and microbial structure of the soil . Therefore, the structure and function of the soil microbialcommunity are often shown to be spatially associated withthe composition, richness and biomass of plant communities, as well aswith stages of plant growth . In addition,it has been believed that the soil microbiota responds quicklyto variations in plant species due to directinteraction between plant roots and soil microorganisms. But this effect is not homogeneousand it is more pronounced on fungal communities than onbacterial communities . However, inaddition to the direct effect of plant species on soil microbialcommunities, the structure and function of plant communitiescan indirectly influence (inhibit or stimulate) these microbialcommunities by altering the physical and chemical propertiesof the soil . Therefore, plant roots exert a strong impact on soilpathogens and beneficial microorganisms in the rhizosphereby producing exudates as well as secondary metabolites . Therefore, the enrichment of plant biodiversityplays a vital role in maintaining the microbial composition ofthe soil, which is not the case with monocultures. This conclusionis confirmed by the works of Schmid et al. (2019) who hastested, over the course of 11 years, soil bacterial communitiesdeveloped under plant monocultures and mixtures. Theseworks confirm that richness in plant species positively affectsthe composition and diversity of microbial communities.Rhizospheric bacterial communities are considered cosmopolitanand colonize all biogeographical regions . However, their activities and their diversities aswell as their distributions are controlled by several parametersof the environment; among these factors, the plant figures asthe major factor that controls them . Someresearch has found conflicting results regarding prediction ofmicrobial diversity by plant diversity when examining theirrelationships at large spatial scales . However,microbial communities are composed of groups that differ intheir behavior. In this regard, we cite the obligate pathogenic or symbiotic microorganisms, the life cycles of which canonly be completed in the presence of their specific host suchas obligate endophytes . Another example can be seen in the caseof ectomycorrhizae, most of which present host-symbiontspecificity . According to these twoexamples, we can only admit that parental control exerted byplant diversity influences the activity and microbial diversityof the rhizosphere. However, the degree of this control differsby several parameters mainly including the nature of microbialgroups, plant species, and also soil and climatic conditions. This explains the sometimes modest correlations betweenmicrobial richness and plant diversity .Bulgarelli et al. (2015) used the term \u2018domestication\u2019 ofbacterial communities by plant roots to explain the dominanceof three bacterial families Comamonadaceae, Flavobacteriaceaeand Rhizobiaceae in the barley root microbiota. On theother hand, a broad conservation of the composition of the rootbacterial microbiota has been found in Arabidopsis thalianaand related species extending over 35 Ma within the familyBrassicaceae . These results mean thatthe host plant determines and maintains its bacterial procession.This control of the soil microbial diversity by the plantsis carried out mainly by the process of rhizodeposition (rootexcretion of photosynthesis-derived organic compounds). These exudates can influence this microbialcommunity either through trophic selection , biochemical selection or by chemotaxis .The main methods by which plant communities affect soilchemical properties and subsequently microbial communitiesare primarily root and leaf litter, and root exudates . Trees produce the majority of the waste depositedon the ground, in addition to a very large part of root exudatesand dead roots under the ground ,which provides different inputs in quantity and quality . It is essential to claim that trees influence thesoil microbiota basically in the same way as other plants, buttheir effect is potentially stronger due to the greater inputbiomass . Therefore, the differencein the quantity and quality of litter and exudate inputs, differentspecies and plant communities, modulates and causesa change in soil microbial communities even at the regional scale .Likewise, several previous studies have reported that differencesin litter quality between tree species affect the abundanceand composition of bacterial and fungal communities inthe soil . In addition,differences in the quality of the litter occur in the nature ofthe inputs; such as the leaching of dissolved organic matterand nutrients, and the exudation of different kinds of ions andorganic compounds . These variations canalter the rate and speed of fundamental soil processes, such asnutrient cycling and carbon dynamics, differently . Consequently, the greatest effect of plant specieson the chemical properties of the soil is observed in thetopsoil corresponding to the greatest amount of organic matterintroduced . From these results, it is clearthat the quality and quantity of litter entering the soil are adetermining factor in the existence of microbial communitiesand needs to be further investigated.Secondary metabolites are another component of plant litter ofparticular interest to soil ecosystems and exert a major effecton their edaphic microflora, especially in forest soils wherecomplex phenol content is significantly higher . Similarly, Santonja et al. (2018) showed a contrastingactivity of bacterial and fungal communities in response tothe diversity of plant litter in a Mediterranean forest. Theseauthors and others have shown that secondary metabolitesrepress biomass and the activity of microbial communities. Likewise,Chomel et al. (2014) showed a strong inhibitory effect ofphenoliccompounds, depending on the concentration, onfungal biomass in a Mediterranean pine forest. On the otherhand, Amaral and Knowles (1998) reported the presence ofmonoterpenes negatively affecting the growth and activity ofcertain soil microbial groups while having a positive effect onother groups. However, knowledge of the effects of secondarymetabolites on the activity and richness of soil microbialcommunities is still very limited.The change in pH is also a consequence of the biogeochemicalinteraction and has a major effect on the composition andactivity of the soil microbial community. Therefore, the pHrepresents the primary metabolic control of microbial communities. This control can be direct,by modulating the thermodynamics and kinetics of redoxreactions and microbial respiration thereafter; or indirect bydetermining salinity and nutrient bioavailability through determinationof proton chemical activity, mineral dissolution andprecipitation, and other geochemical reactions . On the other hand, soil pH describes the extracellularenzymatic activities and the rate of decomposition of organicmatter .It has been reported that changes in the composition anddiversity of microbial communities are positively correlatedwith variation in soil pH and that this variation controls theirspatial distribution in the rhizosphere .This distribution was lower in monoculture plantations thanin natural forests . As reported in thestudy of Chen et al. (2015b), soil acidification decreased soilmicrobial respiration in forest ecosystems. These results suggestthat reducing soil pH can lead to decreased biodiversity,rates of biogeochemical cycling, and ecosystem functioning. Unlike bacterial communities, soilacidification has a slightly favorable effect on the richnessof fungi in forest ecosystems . Thus, theadvanced knowledge of these interactions (pH-fungi-bacteria)can be a very powerful tool to mitigate negative effects causedby pathogenic fungi or bacteria by increasing or decreasingsoil acidity.The climatic conditions of soil ecosystems constitute oneof the most determining parameters of the distribution ofmicrobial communities. Previous research has confirmedthat the spatial variation of soil microbial biomass dependson the spatial heterogeneity of climatic conditions . This justifies the use of microbiological properties asbetter indicators of soil quality, in particular the great capacityof microbial communities to react quickly to environmentalchanges . As an example, several studieshave reported that the mean annual temperature and mean annualprecipitation show a positive correlation with microbialabundance and diversity .Also, low soil moisture and dry conditions during the summerdrought period have a negative effect on microbial diversityand richness. These types of conditions can make a specificselection through the selection of drought resistant taxa suchas fungi with lower nutritional requirements and higher wateracquisition capacity or Gram positive bacteria .From these results and the fact that soils belonging to thesame climatic types have similar properties, we can concludethat climatic factors are of great importance for biodiversityand the richness of microbial biomass in the soil. It alsosuggests that soil microbes could be used as a more preciseindicator of soil ecosystem characteristicsLittle is known about the effects of the physical propertiesof soil on the plant-microorganism interaction. However,the physical properties of soil have been reported to causeprofound changes in soil microbial communities . In addition to the physical propertiesof soil, the biomass and activities of fungal and bacterialcommunities also change at different depths of the soil profile. This vertical distribution revealsthat fungi predominate in the topsoil of the soil, generallybetween 0 and 10 cm deep, and bacteria and actinomycetespredominate deep soils between 40 and 100 cm deep .Nevertheless, it remains necessary to understand how physicalproperties, especially mechanical ones, can influence themicrobiome residing in the soil and what mechanisms themicrobiome can use to combat these types of stresses.Microbial biodiversity is essential for improving sustainableplant growth and maintaining homeostasis of the entirerhizospheric ecosystem. In return, maintaining and enrichingplant biodiversity greatly contributes to the conservation ofsoil microbial diversity. 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To better understand species boundaries and relationships within the T.fuscipes group, we conducted phylogenetic analyses of five plastid regions and morphological observations of herbarium specimens and living plants. As a result, we produced a generally well-resolved phylogeny of the T.fuscipes group and related species in Asia. The phylogenetic analyses supported the monophyly of the T.fuscipes group, which includes T.dissecta, T.fuscipes, T.ingens, T.paradoxa, T.setulosa, T.subfuscipes, T.subsageniacea and a new species, but excludes T.kusukusensis. However, T.fuscipes, T.subfuscipes and T.subsageniacea are almost indistinguishable in morphology, which form a complex characterised by the black linear-lanceolate stipe scales. The new species found in southern China and Vietnam is described here as T.fungii. It is similar to the T.fuscipes complex and T.kusukusensis, but differs from the former mainly by its brown-castaneous lanceolate stipe scales and from the latter by having nearly hairless laminae .The fern species Tectaria Cav. is a pantropical and south-temperate fern genus of about 264 species C. Chr. and morphologically similar species constitute a taxonomically confusing group. They are characterised by the fronds with basal pinnae basiscopically produced and veins being wholly free or, as in T.fuscipes, with veins anastomosing to form costal areoles in its sterile fronds (T.fuscipes and free veins include T.dissecta (G. Forst.) Lellinger, T.fuscipes, T.ingens (Atk. ex C.B. Clarke) Holttum, T.kusukusensis (Hayata) Lellinger, T.setulosa (Baker) Holttum, T.paradoxa (F\u00e9e) Sledge, T.subfuscipes (Tagawa) C.M. Kuo and T.subsageniacea (Christ) Christenh. , Ctenitopsisglabra Ching & Chu H. Wang (Ctenitopsisacrocarpa Ching (T.fuscipes. The first author (Dong) agreed with a broad concept of T.fuscipes sensu T.fuscipes , lamina hairs, fronds dimorphism, venation and sori distribution, which were characters frequently used by previous authors studied in person the specimens of ors e.g. to recogTectaria (Tectariafuscipes s. l. (including T.subfuscipes and T.subsageniacea) and representatives of all known species with free veins in mainland Asia and adjacent islands, except for T.hennipmanii (Tagawa & K. Iwats.) S.Y. Dong, a very rare species and hitherto represented only by its type from Thailand. Of the 51 specimens, 23 were newly sequenced and analysed in this study used in previous studies , Maximum Likelihood (ML) and Maximum Parsimony (MP), respectively. The software jModeltest2 , saving 100 trees per replicate. Bootstrap values (BS) were calculated with 1000 heuristic bootstrap replicates, one random sequence addition and TBR swapping.We analysed the matrix using Bayesian Inference from Bangladesh.Based on the abundance of hairs on the abaxial surface of costae, which are easily observable in herbarium specimens, the fronds can be generally recognised as either nearly hairless or obviously hairy for T.fuscipes group are more or less dimorphic, i.e. a fertile lamina being contracted to a certain extent as compared with a sterile lamina in a population. Our observations showed that the obvious dimorphism of fronds is frequent in T.fuscipes, sometimes occurs in T.subsageniacea, but is scarce in other species of the T.fuscipes group including the unidentified taxon. However, it is difficult to determine the fronds as monomorphic or dimorphic for T.fuscipes and T.subsageniacea because the variation from monomorphic to dimorphic is gradual and continuous. We detected different variation tendencies of frond dimorphism instead of clear differences in these two taxa. Namely, the fronds tend to be dimorphic in T.fuscipes, but are mostly nearly monomorphic in T.subsageniacea. Notably, we observed three different states in a single collection of T.fuscipes from Bhutan Fig. , which iT.fuscipes group can be recognised as three states: free on other pinnae of the same frond. The intermediate venation occurs frequently in T.subfuscipes from Taiwan Island, T.subsageniacea in southern China and Indochina and T.fuscipes in north-eastern India and nearby regions of East Himalayas. Our statistics showed that, in East Himalayas, there are about 54.7% of herbarium specimens of T.fuscipes having the free or intermediate venation; for T.subfuscipes from Taiwan Island, there are about 15% of herbarium specimens having the intermediate venation. Notably, we found that the free venation and the costal-vein-anastomosing venation can simultaneously occur in a single collection from north-eastern India .The venation in the ree Fig. , intermeree Fig. and costree Fig. . The cosT.fuscipes group. They are medial (positioned between mid-rib and margin) and are distributed nearly from base to tip on ultimate segments accounts for 5865 base pairs, including 64 indels. Of the total 5865 characters, 1027 are variable and 688 are parsimony informative. The length of the best MP trees is 1763 . The likelihood score of the ML tree is -18708.288.The concatenated alignment of the five plastid regions analysis and that of MP analysis, except for the position of T.subglabra (Holttum) S.Y. Dong, which was resolved as sister to T.aurita (Sw.) S. Chandra and T.nayarii Mazumdar in the MP tree with low support (MPBS = 68%), while as sister to T.profereoides (Christ) S.Y. Dong and allied species in the BI or ML tree with poor support . There is no conflict involving the position of the T.fuscipes group and species relationships within this group between the trees inferred from different analyses. Therefore, we adopt the topology resulting from the BI analysis Christenh.) clustered into another clade (Clade B) Christenh. Within the T.fuscipes group, all samples were further resolved into three clades: (1) the unidentified taxon represented by three specimens, (2) T.paradoxa, T.ingens and T.setulosa and (3) T.dissecta, T.fuscipes, T.subfuscipes and T.subsageniacea. The unidentified taxon was resolved as sister to the T.paradoxa clade with poor support values.All in-group samples were resolved into two large clades and each clade generally corresponds to a geographical region. The samples from Malesia clustered into a clade (Clade A) and those from mainland Asia and adjacent islands (except for B) Fig. . The T.fTectariafuscipes s. l. (including T.subfuscipes and T.subsageniacea) were well resolved into three clades. All specimens of T.fuscipes s. str., including one (Knapp 3200) with a morphology similar to T.subfuscipes, clustered together, forming a sister clade to the rest. All specimens of T.subsageniacea from mainland China and Vietnam were well resolved in a clade, forming a sister relationship with the clade containing three specimens of T.subfuscipes from Taiwan Island and one T.subfuscipes-like specimen from India.The 16 specimens representing Tectariafuscipes group. As shown in the phylogenetic tree formed a relatively independent, well-supported subclade in Clade B. Its herbarium specimens were frequently misidentified as T.fuscipes sensu T.kusukusensis (Ctenitopsiskusukusensis (Hayata) Ching). The new species differs from T.fuscipes s. l. (including T.subfuscipes and T.subsageniacea) mainly in the brown or castaneous and relatively broad stipe scales bearing sparse and short hairs (ca. 0.5 mm) and sori on anastomosed veins or non-apical on free veins C.W. Chen & C.J. Rothf., T.sabahensis C.W. Chen & C.J. Rothf. and T.gymnocarpa Copel. analysed in this study. As shown in the tree produced by T.paradoxa was not sampled and complete sequences are available for all accessions in the T.fuscipes group, T.fungii (then named Tectaria sp.1) was well resolved as sister to T.setulosa. Therefore, it is expected that the relationships between the new species and other species will be well resolved when better DNA materials are available for T.paradoxa.Within the Islands . The remT.fuscipes, T.subfuscipes and T.subsageniacea as three different lineages fronds , because the fertile fronds are contracted to different extents as compared with the sterile fronds in all these species nor is it possible to draw a line between the two states of fronds. In our opinion, T.fuscipes, T.subfuscipes and T.subsageniacea constitute a species complex which are currently indistinguishable in morphology.According to the current sampling, the phylogenetic analyses supported ges Fig. . However) fronds . In factKnapp 3198, 3199, 3200, which exhibit gradually varied states of frond dimorphism and venation, but were resolved into two clades in the phylogenetic tree from southern Yunnan was reported by x) somatic chromosome numbers and sexual reproduction. One specimen (Dong 3557) also from southern Yunnan was examined having the same number (2n = 80) (unpubl. data). To better understand the morphological variations amongst T.fuscipes, T.subfuscipes and T.subsageniacea, more cytological and reproductive data, as well as more sampling in phylogenetic analyses, are needed.We noticed three collections from the same locality , i.e. ree Fig. . This reTaxon classificationPlantaePolypodialesTectariaceae\ufeffS.Y. Dongsp. nov.1FD17A96-2885-5162-8D00-18247BECAE01urn:lsid:ipni.org:names:77297479-1China. Hainan: Lingshui, 3\u201320 May 1932, H. Fung 20093 .Tectariafungii is similar to the sympatric species T.subsageniacea and T.kusukusensis. It differs from T.subsageniacea in its broader (1\u20131.5 mm versus 0.5\u20131 mm), brown or obviously bicolour (castaneous with brown margins) (versus black) stipe scales and from T.kusukusensis by its nearly hairless laminae .Rhizome short, erect. Fronds slightly dimorphic, rarely obviously dimorphic. Stipe stramineous or dark brown, ca. 4 mm in diameter, 50\u201360 cm long, bearing copious scales towards base and fewer on upper part. Scales lanceolate, ca. 6\u20137 \u00d7 1\u20131.5 mm, brown or castaneous with pale margins. Lamina oblong, 55\u201378 \u00d7 30\u201345 cm, round at base, somewhat suddenly narrowed and acute towards apex, 1-pinnate-pinnatifid, free pinnae (6) 9\u201312 pairs; basal pinnae triangular, deeply lobed to 1-pinnate at base, (18) 24\u201326 \u00d7 13\u201318 cm, shortly stalked (0.5\u20132 cm), with basal basiscopic 2\u20133 pinnules free and markedly prolonged (up to 16 \u00d7 3.5 cm), pinnatifid upwards, acuminate at apex; suprabasal pinnae linear, 16\u201324 \u00d7 3.8\u20135 cm, sessile or very shortly stalked, deeply lobed 2/3\u20133/4 of the way to costae, with a pair or only the basal basiscopic lobes almost free; lobes or pinnules anadromous on basal pinnae and catadromous on pinnae above, basal acroscopic lobes slightly prolonged and parallel to rachis, basal basiscopic lobes obliquely spreading, lobes entire , obtuse or acute at apex, sterile lobes larger, usually 2\u20132.4 \u00d7 0.8\u20130.9 cm, fertile lobes 1.6\u20131.8 \u00d7 0.6 cm. Veins free, simple or mostly once forked. Hairs short, relative dense on adaxial surface and sparse on abaxial surface of costae; no hairs on abaxial surface between veins; with a few hairs on adaxial surface of lamina, especially on margin and at sinus between lobes. Sori terminal on simple veins or on the acroscopic branch of a forked vein, in one row on either side of mid-rib of lobes, medial between mid-rib and margin of lobes. Indusia round-reniform, ca. 1 mm in diameter, persistent, usually ciliate at margin.Hainan: Baisha, S.Y. Dong 728 (PE); Baoting, G.A. Fu 2951 (IBSC); Ledong, S.Y. Dong 1589 (IBSC); Qiongzhong (Mt. Limushan), S.Y. Dong 832 (PE); Mt. Wuzhishan, C. Wang 35347 ; S.Y. Dong 5096 (IBSC), Wuzhishan Fern Survey 036, 176, & 498 (PE); Mt. Yinggeling, S.Y. Dong 3834, 3842, 3867, 4430 (IBSC). Yunnan: Jinghong, B.G. Li 98162 (HITBC), Q.J. Li 42730 (HIBTC); Menghai, W.M. Chu et al. 15749 , H. Shang SG2638 (CSH), X.L. Zhou 5727, 5731 (CSH); Mengla (Bubeng), S.Y. Dong 4307, 4334, 4825 (IBSC). VIETNAM. Dak Nong: Dak Plao, L. Averyanov et al. 5589 (HN), 5601 .China. China and Vietnam (Dak Nong); terrestrial in montane rainforest, occurring in dense-shady and wet slopes, elev. 600\u20131300 m, locally common.The specific epithet honours Mr. Hom Fung, who collected lots of plant specimens in Hainan and Guangdong, southern China in 1930s. This species was probably first collected by him from Hainan in 1932."} +{"text": "In this article the original date was 2018 has been listed as 2021 with an additional author in the reference.This has been corrected with this erratum.The correct reference is given below.Wei, H.-T., Hsu, J.-W., Huang, K.-L., Bai, Y.-M., Su, T.-P., Li, C.-T., Lin, W.-C., Tsai, S.-J., Pan, T.-L., & Chen, T.-J. (2018). Timing of the diagnoses of attention deficit hyperactivity disorder and autism Spectrum disorder in Taiwan. Journal of Autism and Developmental Disorders, 1\u20138."} +{"text": "Wiedemannia zetterstedti group are studied and species definitions are re-evaluated. A new species is described from Corsica (France) and two species synonyms are proposed. The species concepts are also investigated using COI barcodes and a key to species is provided.The aquatic dance fly species of the Wiedemannia zetterstedti species group is revised after examination of all available type specimens and includes one new species (W. ulrichi Ivkovi\u0107 & Sinclair sp. nov.) and four redescribed species (W. czernyi (Bezzi), W. longipennis (Mik) stat. rev., W. rufipes (Oldenberg) stat. rev. and W. zetterstedti ). The following new synonyms are proposed: W. (Roederella) ouedorum Vaillant, 1952 = W. czernyi ; Paramesia riparia Robert, 1836 = W. zetterstedti . Lectotypes are designated for the following species/subspecies: Atalanta hirtiloba Speiser, Brachystoma escheri Zetterstedt, Clinocera czernyi Bezzi, Clinocera longipennis Mik, Paramesia riparia Robert, and Roederia czernyi rufipes Oldenberg. In addition to morphological evidence, molecular species concepts were investigated using a molecular phylogenetic divergence-based species delimitation (bPTP) and results confirmed the morphological conclusions. A key to species is presented and geographic distributions are mapped.The Wiedemannia Zetterstedt is a common empidid in streams and small rivers of Europe \u201d (MSNM). PARALECTOTYPES: same data as lectotype [dissected] ; same data as lectotype except, 4.viii.1897 ; same data as lectotype except, 9.viii.1897 .labelled C: \u201cAcquaNotes on type material. Bezzi \u201d (OUMNH). PARALECTOTYPE: same data as lectotype, except 1.6.1871 [dissected] .Notes on type specimens. This species was described on the basis of an undetermined number of male and female specimens, and Mik \u201d (SDEI). PARALECTOTYPES: Same data as lectotype ; Mehadia, 26.vi.[19]12, Oldenberg .ecies) \u2642 B, labellecies) \u2642 C: \u201cMehadNotes on type material. Oldenberg (by lectotype designation). Clinocera zetterstedti: Loew 1858: 249 \u201d; \u201cLECTOTYPE/of Paramesia/riparia Robert/des. B.J. Sinclair 1999 [red label] (MNHM). PARALECTOTYPES: same data as lectotype except, ED6074 ; same data as lectotype except, ED6075 ; same data as lectotype except, ED6076, Paramesia ripara (=Wiedemannia pirata Mik).Note on type specimens.Wiedemannia zetterstedti, W. escheri and W. hirtiloba were all described on the basis of an unspecified number of male and female specimens , 7\u20139.ix.1990, B.J. Sinclair . Denmark: Endrupholm, 18.vii.1920, P. Nielsen . Germany: Ahrtal, Schuld, 250 m, 16\u201317.vi.2001, Ahr, B.J. Sinclair ; Bonn, Sieg, 25.v.2003, B.J. Sinclair ; Dachau, 18.vii.1913 ; Moseltal, Zell, 11.viii.2001, Altlayer Bach, B.J. Sinclair .Diagnosis. This species is distinguished from other species of the Wiedemannia zetterstedti group by the following combination of characters: face brownish in both sexes, without stripe; wing usually shorter than 5 mm; stout erect setae on costa beyond humeral crossvein; clasping cercus brown, similar to epandrium, with lobes not in same plane and prominent anterior lobe.Redescription. Wing length 3.4\u20134.8 mm. Male .After a thorough morphological study of all available type material and additional material of all species that belong to the iolowski , are synm Collin that Engm Collin was incoWiedemannia zetterstedti is distributed in northern and central Europe [Wiedemannia sp. A). Wiedemannia longipennis is present from Romania, through the Balkan Region and Greece to Turkey, Georgia, and Lebanon and is present in the northern and central part of Italy. Wiedemannia czernyi is present in Italy, Spain, southern France, and Northern Africa (Morocco and Algeria), while W. rufipes is presently known only from Romania, Greece, and Georgia.The geographical distribution by country of all species is given in l Europe , with pal Europe and the l Europe (as Wied"} +{"text": "These feelings can include pleasure and pain, but also others such as hunger, curiosity, loneliness, and fear. Animal sentience plays an important role in ethical deliberations, as sentient animals are capable of suffering, a capacity frequently taken to ground moral status. It is also increasingly relevant for policy looking to protect the welfare of animals. Precautionary reasoning can be used to award protection to taxa for which there is some reasonable evidence of sentience, even if this evidence is not definitive. The subjective nature of sentience makes it a difficult scientific target. However, there are an increasing range of indirect indicators that can be used together to infer sentience, including those based on the differences in conscious vs unconscious performance by humans on perceptual and learning tasks, and those based on proposed evolutionary functions of sentience. These indicators can then be used to guide inferences about the distribution of sentience throughout the animal kingdom. There is now wide agreement that there is sufficient evidence to warrant the attribution of sentience to most vertebrates, though some sceptics still question the case for fish. Current work on is also suggestive of sentience in some invertebrates, including cephalopod molluscs and decapod crustaceans.Animal sentience, in a broad sense, refers to the capacity of an animal to have feelings with a subjective character. If an animal is sentient, there is 2https://www.lse.ac.uk/business/consulting/assets/documents/Sentience\u2010in\u2010Cephalopod\u2010Molluscs\u2010and\u2010Decapod\u2010Crustaceans\u2010Final\u2010Report\u2010November\u20102021.pdfBirch, J., Burn, C., Schnell, A., Browning, H., & Crump, A. (2021). Review of the Evidence of Sentience in Cephalopod Molluscs and Decapod Crustaceans. This report provides a framework of indicators of sentience for assessing the likelihood of sentience in any given taxa; and an assessment of the literature on in relation to these indicators in cephalopod molluscs and decapod crustaceans.https://doi.org/10.1016/j.applanim.2006.04.011Duncan, I. J. (2006). The changing concept of animal sentience. Applied Animal Behaviour Science, 100, 11\u201019. Gives a history of the concept of sentience and its use within science and the general public from the 15th Century through to today. Discusses some of the scientific challenges in studying sentience, and where further research is needed.Godfrey\u2010Smith, P. (2016). Other minds: The octopus, the sea, and the deep origins of consciousness. New York: Farrar, Strauss and Giroux.Using stories and examples taken from the author's own experiences while scuba\u2010diving, this book describes the unique minds of octopuses and traces the possible evolutionary origins of consciousness.https://doi.org/10.1007/s10539\u2010012\u20109351\u20101Jones, R. C. (2013). Science, sentience, and animal welfare. Biology & Philosophy, 28, 1\u201030. This paper discusses the role of sentience in moral status and animal welfare policy, summarising the current research on the sentience of a range of nonhuman animals.https://fcmconference.org/img/CambridgeDeclarationOnConsciousness.pdfLow, P. . The Cambridge declaration on consciousness. Presented at the Francis Crick Memorial Conference, Cambridge, England. This document represents a foundational shift in the study of animal sentience \u2010 a declaration by a group of prominent neuroscientists that the weight of evidence was sufficient to conclude that at least some non\u2010human animals are conscious.Nagel, T. (1974). What is it like to be a bat? Philosophical Review, 83, 435\u2010450.The classic introduction to the problem of studying the minds of other animals \u2013 providing an understanding of what it means to be sentient and the limitations of our intuitive understanding of minds very different from our own.https://doi.org/10.3390/ani3030882Proctor, H. S., Carder, G., & Cornish, A. R. (2013). Searching for animal sentience: A systematic review of the scientific literature. Animals, 3(3), 882\u2010906. Though now slightly out of date, this article provides a thorough review of the literature on animal sentience at the time, showing trends, areas of focus, and knowledge gaps.33.1https://www.lse.ac.uk/cpnss/research/ASENTWebsite with the latest research outputs of the authors' research project into animal sentience.3.2https://www.wellbeingintlstudiesrepository.org/animsent/An open\u2010access journal containing target articles and commentaries on a variety of issues in animal sentience.3.3https://science.rspca.org.uk/sciencegroup/sentienceDescribes the importance of sentience and how to help the welfare of sentient animals, provides links to the outcomes of a 2019 conference on the topic.44.1What is sentience, and what role does it play in ethics and public policy?Birch, J. (2017). Animal sentience and the precautionary principle. Animal Sentience, 2(16), 1.Nagel, T. (1974). What is it like to be a bat? Philosophical Review, 83, 435\u2010450.Singer, P. (1979). Practical ethics. Cambridge: Cambridge University Press. \u2013 Chapter 3: Equality for animals?Readings:4.2How can scientists gain understanding of sentience, its function, mechanisms, and distribution?Ben\u2010Haim, M. S., Dal Monte, O., Fagan, N. A., Dunham, Y., Hassin, R. R., Chang, S. W., & Santos, L. R. (2021). Disentangling perceptual awareness from nonconscious processing in rhesus monkeys (Macaca mulatta). Proceedings of the National Academy of Sciences, 118, e2017543118.https://doi.org/10.1111/nous.12351Birch, J. (2020). The search for invertebrate consciousness. No\u00fbs. Advance online publication, Birch, J., Schnell, A. K. & Clayton, N. S. (2020b). Dimensions of animal consciousness. Trends in Cognitive Sciences, 24, 789\u2010801.Boly, M., Seth, A.K., Wilke, M., Ingmundson, P., Baars, B., Laureys, S., Edelman, D. and Tsuchiya, N. (2013). Consciousness in humans and non\u2010human animals: Recent advances and future directions. Frontiers in Psychology, 4, 625.Nieder, A., Wagener, L., & Rinnert, P. (2020). A neural correlate of sensory consciousness in a corvid bird. Science, 369, 1626\u20101629.Paul, E. S., Sher, S., Tamietto, M., Winkielman, P., & Mendl, M. T. (2020). Towards a comparative science of emotion: Affect and consciousness in humans and animals. Neuroscience & Biobehavioral Reviews, 108, 749\u2013770.Readings:4.3Critical discussion of the evidence of sentience across a range of \u2018controversial\u2019 taxa, such as fish, cephalopod molluscs, and decapod crustaceans.Appel, M., & Elwood, R. W. (2009). Motivational trade\u2010offs and potential pain experience in hermit crabs. Applied Animal Behaviour Science, 119, 120\u2013124.https://www.lse.ac.uk/business/consulting/assets/documents/Sentience\u2010in\u2010Cephalopod\u2010Molluscs\u2010and\u2010Decapod\u2010Crustaceans\u2010Final\u2010Report\u2010November\u20102021.pdfBirch, J., Burn, C., Schnell, A., Browning, H., & Crump, A. (2021). Review of the Evidence of Sentience in Cephalopod Molluscs and Decapod Crustaceans.Crook, R. J. (2021). Behavioural and neurophysiological evidence suggests affective pain experience in octopus. iScience, 24, 102229.Key, B. (2016). Why fish do not feel pain. Animal Sentience, 3, 1.Michel, M. (2019). Fish and microchips: On fish pain and multiple realization. Philosophical Studies, 25, 95\u2010110.Sneddon, L. U. (2009). Pain perception in fish: indicators and endpoints. Institute for Laboratory Animal Research Journal, 50(4), 338\u2010342.Readings:5What is sentience?What is the ethical significance of sentience?How should sentience guide public policy?How can we study sentience?Which animals are sentient?6Practical assignment: Assessing the evidence for sentience.Choose one of the following taxa: insects, gastropod molluscs, or spiders. Argue for or against sentience in this taxonomic group, providing reasons for your judgement ."} +{"text": "The original S.O.L.V.E. scoring system was modified using virtual reality technology, and a new H.L.P.E.S scoring system was constructed to improve the accuracy of predicting the stone-free rate after flexible ureteroscopy.We retrospectively analyzed clinical and virtual reality data of 150 patients with renal calculi who underwent flexible ureteroscopy at the First Affiliated Hospital of Chongqing Medical University, Chongqing, China, from September 2019 to January 2022. Factors affecting the stone-free rate were evaluated in univariate and multiple logical regression analyses. Factors were divided by cut-off value under the receiver-operating characteristic curve and scored accordingly to a well-known international scoring system. Area under the curve predicted the stone-free rate. The accuracy and superiority of the stone-free rate after flexible ureterorenoscopy was compared between this scoring system and the S.O.L.V.E, R.I.R.S, T.O.HO, and RUSS scores.P\u2009<\u20090.01, P\u2009=\u20090.021, P\u2009=\u20090.019, respectively). The H.L.P.E.S. score included stone surface area (1\u20132 points), renal pelvis volume (1\u20132 points), length of calyces funnel (1\u20132 points), pelvic calyceal height (1\u20132 points), and essence of stone (1\u20132 points). The area under the receiver-operating characteristic curve of H.L.P.E.S. score was 0.927, which was higher than the S.O.L.V.E., R.I.R.S., T.O.HO, and RUSS scores.Multiple logistic regression showed that the stone surface area, renal pelvis volume, and length of the calyces funnel were correlated with stone-free rate (H.L.P.E.S. scoring can effectively predict the stone-free rate after flexible ureteroscopy for renal calculi and is superior to other scoring systems. Urolithiasis is one of the most common urological diseases. The epidemiological data of Europe and America show that 5\u201310% of the population experiences urolithiasis at least once in their lifetime, and the new incidence rate is 100 \u2212\u2009400/100,000 . AlthougThis study was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. We retrospectively collected clinical data and data related to VR measurements from 150 patients with renal calculi treated with FURS in our hospital between September 2019 and January 2022. No preoperative CT of urography (CTU) or VR image processing and renal anatomical abnormalities were excluded.CTU was obtained and VR techniques were used to measure the stone surface area, renal pelvis volume, length of the calyces funnel, essence of stone, and pelvic calyceal height. All measurements were obtained using a holographic 3D image reconstruction system . FigureA total of 150 patients with renal calculi underwent FURS under general anesthesia. First, we used F8/9.8 rigid ureteroscopy to examine the ureteropelvic junction with a 0.038-inch zebra guidewire. An F12/14 ureteroscopic sheath was inserted into the ureteropelvic junction along the guidewire, and ureteroscopic examination of the renal pelvis and calyces was performed. We inserted a 200-\u00b5m holmium laser fiber through the operation channel. The laser energy and frequency were set to 1.2J/15\u201320Hz. The stone was crushed to <\u20094mm by the holmium laser. The larger stone was removed from the body using a sleeve basket. After the operation, an indwelling F16 catheter and F6 ureter stent were placed.A patient was defined as stone-free when no residual stone or residual fragments\u2009<\u20094mm were detected on kidney, ureter, and bladder X-ray imaging carried out 1 month after surgery .The measurement data of normal distribution or of approximate normal distribution are expressed as the mean\u2009\u00b1\u2009standard deviation, and the measurement data of partial distribution are expressed in terms of median (minimum to maximum). The relationships of evaluation factors with stone-free status were analyzed using chi-square test or a two-tailed unpaired Student\u2019s t-test. All possible predictors were analyzed by univariate analysis, and statistically significant predictors were included in the multivariate analysis. We used a logistic regression model to analyze the relevant factors affecting the SFR, and we calculated the cutoff values of each factor by drawing the receiver-operating characteristic (ROC) curve; the value was used as the boundary value of each factor. We calculated the value of the area under the curve (AUC) of the HLPES scoring system to predict the SFR. We compared the AUC of the H.L.P.E.S. with that of the S.O.L.V.E, R.I.R.S, T.O.HO., and RUSS scores. P\u2009<\u20090.05 was considered statistically significant. We used SPSS software for statistical analyses.2 , 25 cases had an indwelling ureteral stent before the operation, 61 cases of calculi located on the left side, and 59 cases of calculi located on the right side. The stone-residual group included 30 cases: 23 men and 7 women, average age 51.00\u2009\u00b1\u200912.23 years, 10 cases a history of stone operation, median body mass index 24.9kg/m2 , three cases had an indwelling ureteral stent before the operation, 19 cases had calculi located on the left side, and 11 cases had calculi located on the right side. TableWe included a total of 150 patients (102 men and 48 women) with a mean age of 49.6\u2009\u00b1\u200912.0 years . Patients were divided according to postoperative stone-free status. The stone-free group included 120 cases: 79 men and 41 women, mean age 49.27\u2009\u00b1\u200911.99 years, 34 cases of previous stone surgery, median body mass index 24.3kg/mThe total SFR after FURS was 80% 120/150). Table20/150. TP value of pelvic calyceal height was >\u20090.05, its odds ratio was >\u20091, which allowed us to consider it a risk factor for residual stones. The results showed that stone surface area, renal pelvis volume, and length of the calyces funnel were correlated with SFR , whereas essence of stone and pelvic calyceal height were not . FigureThe revised scoring system includes the stone surface area, essence of stone, renal pelvis volume, length of calyces funnel, and pelvic calyceal height. For each factor, the cut-off values are taken as the boundary values. Each variable is assigned a value in reference to the previous literature and the original S.O.L.V.E score \u20139: (S)toWe constructed the new H.L.P.E.S. score by incorporating the five variables mentioned above. FigureTo further verify its accuracy and predictive value, we compared the H.L.P.E.S. score with the existing R.I.R.S., RUSS., S.O.L.V.E., and T.O.HO. scores, as shown in Fig.The technology used in medical optical equipment, laser equipment, and auxiliary material equipment has developed rapidly, and the treatment of renal calculi has changed greatly. FURS has many advantages over other methods, including higher SFR, less trauma, and quicker recovery. FURS has quickly become an effective minimally invasive method for treating renal calculi. SFR is the ultimate goal of all surgeons, but FURS removes kidney stones through the body\u2019s natural lumen; thus, many factors affect SFR after FURS, including urinary system anatomy and stone characteristics. Because the preoperative point of departure of stones with identical sizes is often different based on the choice of surgical treatment, differences occur in SFR, which affects the surgical results. Patients would undoubtedly benefit from an evaluation system that can effectively predict the preoperative stone removal rate and guide the prediction of surgical methods. Previously, some errors were found in the accuracy and measurement methods of the S.O.L.V.E scoring system, limiting its clinical value. With the recent widespread application of VR in the surgical field, we can accurately evaluate the effect of FURS using the H.L.P.E.S. score and VR before the operation, which will assist clinicians in determining optimal treatment. Previous scoring variables remain an important factor for predicting SFR, but the accuracy of variable measurement is limited by imaging techniques; thus, the value of the prediction is affected. The new scoring system retains the previous stone surface area, length of calyces funnel, and essence of stone and adds renal pelvis volume and pelvic calyceal height. In addition, VR technology application makes the measurement of each variable more accurate and will undoubtedly greatly improve the prediction accuracy.Essence of stone leads to variations in operation time. Ito et al. found a 3 [P\u2009=\u20090.002) between the non-residual group and the residual group, and as the score increased, there was a significant difference in postoperative SFR (P\u2009<\u20090.01) between the groups [The stone surface area is an important factor in the absence of residual stones and was 3 . The stu3 found th3 increasee groups .P\u2009=\u20090.019). The longer the infundibular part of the calyx, the more difficult it is to treat calculi with FURS, and the more difficult it is to remove calculi.The calyces funnel length is an important factor affecting SFR after FURS. A renal calyx infundibulum that is too long will result in a large distance from the renal calyx stone to the renal pelvis, leading to residual stone. Geavlete et al. found th3 [P\u2009=\u20090.021) between the non-residual group and the residual group.Renal pelvis volume is another important factor affecting SFR after FURS. Severe hydronephrosis leads to enlargement of the kidney volume and affects the ureteroscopy flexibility. It is easy to miss in the process of searching for stones , which l3 , and theIn this study, we measured pelvic calyceal height, which is the length of the vertical line from the base of the calyx to the junction of the pelvic and calyx. This measurement was assigned two points, with a boundary of 21mm. The mean height of the group without residual stone was lower than that of the group with residual stone, which was nearly significant in the single-factor analysis but had no statistical difference in the correlation analysis. We believe that the greater the height and the deeper the depth of the soft lens into the kidney, the more flexible the soft lens will be. The more difficult the calculus is to drain, the more likely it is that there will be residual calculus. Nevertheless, the new H.L.P.E.S. scoring system, which incorporates the height and density of the pelvic and calyx into the scoring system, has an AUC of 0.927, indicating that it is still valuable for postoperative comprehensive prediction of SFR. However, further study is needed with more cases. In their study, Symes et al. concludeIn the correlation analysis of H.L.P.E.S. score variables, the H.L.P.E.S. score for SFR was 0.927, which is higher than for any of the variables in the score. Comparisons were made with the existing R.I.R.S., RUSS., S.O.L.V.E., and T.O.HO. scores. H.L.P.E.S. had an AUC of 0.927, which is higher than any of the other scores. The cut-off value of the H.L.P.ES score was the same as that of the R.I.R.S. score or the T.O.HO. score, but the H.L.P.E.S. score had higher in sensitivity and specificity. The new H.L.P.E.S. score was superior to the previous S.O.L.V.E. score in terms of cut-off value, sensitivity, and specificity. The RUSS score was superior to the cut-off value and sensitivity values of each scoring system, but its specificity and AUC values were significantly lower than the newly established H.L.P.E.S. score. Therefore, we believe that this scoring system is superior to other scoring systems. Of course, this study is was single-center, retrospective study with a relatively small sample size, and the results might include selective bias. Thus, we must expand the sample size and actively carry out multicenter, prospective studies to improve the reliability and practicability of the results.In conclusion, the H.L.P.E.S. scoring system based on VR technology combined with the revised S.O.L.V.E. score can be used not only to evaluate and more accurately predict the calculus clearance rate after FURS but also to strengthen the communication between doctors and patients using the help of VR technology, so as to guide the choice of operation method and achieve accurate medical treatment. The relevant measurement data used in the H.L.P.E.S. scoring system can be easily obtained, and the score itself is of simple, operable, and has a higher predictive value, making it superior to other scoring systems."} +{"text": "Adv. Sci. 2021, 8, 210145810.1002/advs.202101458DOI: In the original published article, the name of Jianlin Wang was spelt incorrectly. The updated author byline is shown above."} +{"text": "Scientific Reports 10.1038/srep17806, published online 03 December 2015Correction to: The Acknowledgements section in the original version of this Article is incomplete.\u201cWe thank A. Simcox, A. Stathopoulos, B. Edgar, the Vienna Drosophila RNAi Center, the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for flies and antibodies; K. Campbell, M. Llimargas, D. Mart\u00edn and F. Wendler for helpful suggestions on the manuscript. J.C. was supported by BFU2009-08748 from the Spanish MICINN and N.B-R. was supported by FPI from the Spanish MICINN. This work was funded by the Spanish Ministerio de Ciencia e Innovacion (Project BFU2009-08748).\u201dshould read:\u201cWe thank A. Simcox, A. Stathopoulos, B. Edgar, the Vienna Drosophila RNAi Center, the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for flies and antibodies; K. Campbell, M. Llimargas, D. Mart\u00edn and F. Wendler for helpful suggestions on the manuscript. J.C. was supported by BFU2009-08748 from the Spanish MICINN and N.B-R. was supported by FPI from the Spanish MICINN. This work was funded by the Spanish Ministerio de Ciencia e Innovacion (Project BFU2009-08748) and Spanish Ministerio de Econom\u00eda y Competitividad (Project CGL2014-55786-P). The research has also benefited from FEDER, UE funds.\u201d"} +{"text": "Many plants and animals have symbiotic relationships with microorganisms, including bacteria. The interactions between bacteria and their hosts result in different outcomes for the host organism. The outcome can be neutral, harmful or have beneficial effects for participants. Remarkably, these relationships are not static, as they change throughout an organism\u2019s lifetime and on an evolutionary scale. One of the structures responsible for relationships in bacteria is O-antigen. Depending on the characteristics of its components, the bacteria can avoid the host\u2019s immune response or establish a mutualistic relationship with it. O-antigen is a key component in Gram-negative bacteria\u2019s outer membrane. This component facilitates interaction between the bacteria and host immune system or phages. The variability of the physical structure is caused by the genomic variability of genes encoding O-antigen synthesis components. The genes and pathways of O-polysaccharide (OPS) synthesis were intensively investigated mostly for Enterobacteriaceae species. Considering high genetic and molecular diversity of this structure even between strains, these findings may not have caught the entire variety possibly presented in non-model species. The current study presents a comparative analysis of genes associated with O-antigen synthesis in bacteria of the Oxalobacteraceae family. In contrast to existing studies based on PCR methods, we use a bioinformatics approach and compare O- antigens at the level of clusters rather than individual genes. We found that the O-antigen genes of these bacteria are represented by several clusters located at a distance from each other. The greatest similarity of the clusters is observed within individual bacterial genera, which is explained by the high variability of O-antigens. The study describes similarities of OPS genes inherent to the family as a whole and also considers individual unique cases of O-antigen genetic variability inherent to individual bacteria The Oxalobacteraceae family belongs to the Burkholderialesorder of Proteobacteria. According to the Integrated TaxonomicInformation System (www.itis.gov) this family includes55 verified species of 12 genera. Members of the Oxalobacteraceaefamily are stained negatively by Gram and presented ina wide range of habitats 1. Species were found in soils, including grassland,volcanic and heavy metal polluted soils, in water and glaciers. Some of them are free-living, othersmay form various relationships with plants. Symbiotic species are known to exhibit plantgrowth-promoting features, and can be beneficial in agriculture. Occasionally, these relationships lead to plant diseases,for example, red stripe and mottle stripe diseases . The negative effect depends on the environmentconditions. Examples of opportunistic features are describedfor Janthinobacterium and Herbaspirillum genera. Some speciescan be found in clinical samples and act as opportunisticpathogens for humans .https://doi.org/10.5281/zenodo.7410337.Supplementary Materials are available in the online version of the paper:Beneficial effects from Oxalobacteraceae bacteria are relatedto agriculture and medicine. Farming industry utilizesthese bacteria to improve plant growth. Mutualistic bacteriafacilitate nitrogen assimilation to increase crops productivity.In medicine, bacterial lipopolysaccharides (LPS) can be usedfor vaccine development. This modern medicine developmentis called glycoconjugate vaccines. The methodology isalready verified on the members of Enterobacteraceae family and can be scaled to other bacteria.Beyond vaccines, information related to LPS lies in biosensorsystems. Systems are able to identify bacteria in samplesbased on their LPS composition, in particular O-antigens.O-antigen became a convenient feature for serotyping dueto its variability. Diversity of the oligopolysaccharide unitsand the selection of the host immune system directed at themhighly contribute to the variability of O-antigens. In addition tothis selection, there is the bacteriophage effect on the bacterialcell . All these factors explain the emergenceof different serotypes within the same bacterial speciesO-antigen is one part of bacterial LPS. Lipopolysaccharidesare a specific structures binding to the outermembraneof Gram-negative bacteria. It consists of three partsthat are linked to each other in a particular order: phospholipidanchored to the membrane (lipid A or endotoxin), core regionand O-antigen repeats. Lipid A is the hydrophobic domain anchoring LPS in the membrane. In chemical structure, lipid A isa phospholipid based on glucosamine. It forms the monolayerof the outer membrane. Lipid A is responsible for the toxicityof Gram-negative bacteria. The second component of LPS isthe core part. The first and the second LPS components aresynthesized on the cytoplasmic side of the inner membraneof the bacterial cell, after which they are transported by ABCtransporters into the periplasmic space . Thethird component of LPS is O-antigen, which is synthesizedseparately from the previous parts. In a periplasmic space, allparts of LPS are combined together, then the fully synthesizedLPS is transported to the outer leaflet of the cell membrane.The composition of LPS and its parts varies between differentspecies and between strains .In some strains O-antigen can be absent, thus referred to as\u201crough\u201d LPS, others containing it are \u201csmooth\u201d . The O-antigen consists of a series of repeatingoligosaccharide units. The length and composition of themonomers vary quite widely among strains . Repeats can be homodimers or heterodimers. In addition,units can be linked linearly or can create a branchedstructure .Sugar nucleotides are basic molecules that form an O-antigenbackbone. The most common can be divided into severalgroups:\u2022 dTDP-sugars (rfb/rml genes);\u2022 CDP-sugars (ddh genes);\u2022 GDP-sugars ;\u2022 UDP-glucoses ;\u2022 UDP-N-acetylglucosamines .Other nucleotide sugar genes include nna genes (N-acetylneuraminicacid synthesis), hdd genes and gmh (LD-mannoheptoseand DD-manno-heptose) and dmh genes of 6-deoxy-D-manno-heptose synthesis pathway .The O-antigen chain is assembled via glycosyltransferases,which are responsible for combinations of sugar nucleotides.The mechanisms of generating O-antigen and flippingare described in two variants: Wzy-dependent pathway andABC-transporter pathway. The former is predominant amongbetter-characterized O-antigens. A third variant is the synthasedependentpathway. Unfortunately, it is poorly described andhas been observed rarely, for instance, in Salmonella species.The initiation of all O-antigen synthesis pathways is a transferof a sugar monophosphate to the undecaprenyl phosphate(Und-P) molecule, resulting in sugar-pyrophosphate-undecaprenyl(sugar-Und-PP). Sugar-Und-PP is able to accept furtherglycosylation reactions .Uniquely to the Wzy-dependent pathway, Und-P-linkedunits are polymerized by Wzy (wzy gene) and subsequentlyflipped via Wzx (wzx gene). The chain length is controlledby Wzz protein (wzz). The completed structure is ligated tothe outer core region via WaaL O-antigen ligase encoded bywaaL (rfaL) gene .On the contrary, the ABC-transporter pathway needs onlya single initiation reaction per O-antigen chain. Moreover,the entire polymerization process via glycosyltransferases iscarried out in the cytoplasm. Then the completely generatedO-antigen-Und-PP molecule is flipped to the periplasmic spaceby an ABC transporter, which is encoded by wzt and wzmgenes. Similarly to the previously characterized pathway, theO-antigen ligase protein WaaL connects it to the core-lipid A.In view of the above described, O-antigen becomes a highlyvariable structure. This feature makes the O-antigen attractiveto a wide range of researchers. Nevertheless, there are ratherfew studies on comparative analysis of O-antigens and theirgenetic structure between bacteria at the family level. Mostpublications are devoted to single pathogenic or potentiallypathogenic bacteria and avoid features of free-living or mutualisticspecies.Detection and study of O-antigens have been made possibleby the emergence of several methods involving bothexperimental and bioinformatics analysis of bacterial data.One of the traditional methods belonging to the first group isthe bacterial glycotyping method based on the somatic antigen.In 2020, E.T. Sumrall et al. (2020) proposed a new methodfor quantitative separation of O-antigens. It is based on theuse of a set of recombinant proteins that can interact withbacterial envelope receptors and domains. Bacterial O- antigenscan also be detected by serological and agglutinationtest methods using sera specific to somatic antigens . Another way to study O-antigen composition isthe polymerase chain reaction method, which is widely usedto compare O-antigens in several bacteria.The emergence and subsequent decrease in the cost of sequencingopened new ways of O-antigen studying. In silicoanalysis methods have significantly reduced the time requiredfor data processing, and many routine processes have beenautomated. Extensive databases have appeared that lead to theO- antigens analysis of several bacteria at once. In comparisonto traditional methods of O-antigen detection, in silicomethods are able to revise taxonomy misunderstandings,identify more genes related to O-antigen biosynthesis andevaluate their environment in a short time. Predicted featurescan be then verified by traditional laboratory methods. On theexample of an Oxalobacteraceae member called Janthinobacteriumsp. SLB01 , the taxonomywas revised by this combined approach.Here we present comparative analysis of O-antigens for 20genomes from the Oxalobacteraceae family. According to thequery in UniprotKB \u201c(protein_name: O-antigen) AND (taxonomy_id:75682)\u201d there are only 456 genes whose proteinsare annotated as O-antigen biosynthesis genes for this family.Our bioinformatics approach based on homologues searcheliminates difficulties in gene annotation. We also shift fromdescribing single genes to comparing O- antigens at the level of their candidate gene clusters to broad information aboutthe gene content of OxalobacteraceaeO-antigens.Data. Initial data was derived from NCBI databases and included20 genomes. The main criterion of assembly selectionwas a rather high quality, that is, no more than ten contigs. Thereason for such a criterion was to decrease the possibilityofgene clusters being disrupted by unresolved sequences. Overall,we selected two Collimonas species (C. arenae and C. fungivorans),one species of genera Herminiimonas (H. arsenitoxidans),Oxalobacter (O. formigenes), and Undibacterium(U. parvum), four Janthinobacterium , two Oxalicibacterium species and nine Massilia. TheirRefSeq assembly accessions are presented in SupplementaryMaterials, Table S2.Quality control and annotation. All 20 assemblies wereadditionally analyzed using QUAST tool, version 5.0.2 . The acceptable threshold number ofcontigsand scaffolds was eleven, only genomes with a lowernumber were selected. To obtain the most precise annotation,we used two annotation tools, Prokka version 1.14.6 and eggNOG version 2.1.6 .Putative O-antigen genes search. Searching for genescoding components for O-antigen synthesis and processingbased on their names was unproductive because of the abundanceof various synonymous tags. Therefore, we used anapproach based on orthology. All O-antigen related genes forEscherichia coli strains described in the paper were obtained with their amino acid sequences and usedas reference. We also added genes from the KEGG database,a pathway of O-antigen synthesis for E. coli https://www.genome.jp/pathway/ecoi00541. We additionally analyzed theO-antigen ligase gene rfaL (waaL), because it was shown thatO-antigen may be absent in some bacteria .As waaL is essential for final stages of O-antigen processingfor the majority of bacteria, its absence may be associated witha lack of OPS on the cell wall . This dataconsisted of gene sets for each serogroup and approximately420 unique genes in total .In order to find unique genes among this data, sequenceswere clustered using UCLUST algorithm withthe usearch32 tool, with threshold identity > 0.4. The reasonfor the rather low threshold was the excessive amount ofclusters at higher numbers, mainly because of high gene variation.For the next step, we chose centroids of each cluster asrepresentative sequences of 27,000 bp in length . However,another important parameter for our definition is genes onborders. Thus, for an array of three genes, if genes on theborders of the set coincide, we also define this set as a cluster.A more detailed investigation of the obtained gene clusterswith respect to their structure, function and sequence similaritywas conducted using eggNOG and BLAST (v.2.5.0+) toolsVerification of the identified candidate genes was performedvia functional Pfam domains search . Lists of domains were obtained manually,from . The HMMERsoftware hmmer.org version 3.3.2 allowed the detection ofthose domains in FASTA amino acid sequences of all genomes.Some genes were checked manually using onlinePfam sequence search https://pfam.xfam.org . Characterization of genes shown to be uninvolved inO-antigen biosynthesis processes was performed using KEGGdatabases .Phylogenetic tree reconstruction. Phylogenetic tree wasconstructed to explore evolutionary relationships betweenthe chosen Oxalobacteraceae taxa. Several species of theBurkholderaceaefamily were selected to create an outgroup. 16S rRNA sequencesfor 13 Oxalobacteraceae species were derived from publishedpapers . Barrnapversion 0.9 (RRID:SCR_015995) was used for seven othergenomes to derive16S rRNA sequences .16S rRNA sequences were aligned using R-coffee, theT-coffee web-server RNA sequences alignment tool . This tool takes into consideration the RNAsecondary structure. Default multiple alignment options werechosen. The resulting alignment was used for constructing aphylogenetic tree using IQ-TREE web server . DNA was selected for sequence type, other optionsremained default. The best-fit model was TN+F+I+G4, the treeconstructed with the Maximum likelihood method. Consensustree was constructed from 1000 bootstrap trees and branchlengths were optimized by Maximum likelihood on originalalignment. The results were visualized using Archaeopteryx0.9928 .Gene clusters visualization. To visualize the found clusterswe developed a Python script based on the DnaFeaturesViewerlibrary (https://edinburgh-genome-foundry.github.io/DnaFeaturesViewer/index.html#more-biology-software). The codeis available on this page https://github.com/svetaafonnikova/O-antigen-project/blob/main/draw_cluster.py. All steps of thedata analysis algorithm are schematically depicted in Fig. 1.Assembly quality characterizationOut of all 20 assemblies, 15 were at the level of completegenomes. M. timonae assembly consisted of a single contigwith N50 equal to the length of this contig. Two assembliescontained plasmid sequences (M. putida and M. violaceinigra).Another pair, O. faecigallinarum and O. flavum, containedten and nine contigs, respectively.Using IGV (v. 2.11.1) we confirmedthat the identified O-antigen gene clusters were notlocated on plasmid fragments in case of plasmid containinggenome assemblies. Secondly, O-antigen gene clusters werenot situatedon the borders of contigs, thus any breaks insideclusters were excluded.Description of gene clustersIn general, almost all of the analyzed species contained morethan two O-antigen gene clusters. These clusters are scatteredaround the genome and include not only O-polysaccharidegenes, but genes of other functions. The visualization for all20 species can be found in Supplementary Materials, Fig. S1.In the text below, we will describe these clusters for eachgenus used in the study.Collimonas. In both C. arenae and C. fungivorans wedetected O-antigen ligase gene rfaL (or waaL) immediatelyadjacent to galE gene involved in nucleotide sugar synthesis.In addition, both genomes contain wzm and wzt genes.Furthermore, they share the same cluster with manB andwfaK on borders. All genes and their order coincide exceptone glycosyltransferase gene wbaS, absent in C. fungivorans.Regarding other differences, the former species consists ofthree clusters, the latter consists of four. One of C. fungivoransclusters contains O-antigen unit synthesis ,processing genes and a triplet of glycosyltransferasegene wbaX. Remarkably, in C. arenae these processingand unit synthesis genes are included in a single cluster withrfbABCD and manB genes on the borders.Herminiimonas. According to our analysis, H. arsenitoxidansgenome possesses three O-antigen gene clusters, withrfaL gene located outside all of them without any OPS genesbeside. Regarding genes involved in processing, only wzx wasobserved. There are duplication instances for L-Rhamnosebiosynthesis gene rfbD, sugar transferase genes wbaT andwbaS. One cluster contains a rather small number of geneswe are interested in compared to not O-antigen ones. Theseunnecessary for OPS production genes partake in phosphatemetabolism.Janthinobacterium. J. lividum carries two clusters andJ. agaricidamnosum comprises three gene clusters involved in O-antigen synthesis, whereas J. svalbardensis and J. tructaeinclude four. The latter two share identical clusters withUDP-N-acetylglucosamine pathway, wbqA and wbqB on theone end and glycosyltransferase gene wbdH on the other.All but J. agaricidamnosum have duplications of rfbABCDgenes. All four genes are duplicated in J. lividum and J. svalbardensis,J. tructae possesses three copies of rfbA and rfbB.Furthermore, the J. tructae cluster with rfbBA and fnlA bordersis almost similar to a part of another larger O-antigen genecluster. In J. lividum and J. svalbardensis we found a commonOPS related gene cluster flanked by wbqB and wbhQ. Thisgene set includes dTDP-glucose pathway genes rfbABCD andvioA. Still, the latter species has glycosyltransferase wbaSnext to wbqB, which J. lividum lacks in this position. To add,wzx gene was located after vioA in J. lividum, however, wedidn\u2019t observe any significant domains for J. svalbardensis inthat position. The O-antigen ligase was observed in all genusmembers. It lies far from any depicted cluster.Considering genes not included in our initial gene list, thereare genes involved in LPS core synthesis (waaD), polysaccharidetransport gene (wza), genes characteristic to O-antigenproduction in other bacteria species .Massilia. According to our analysis, Massilia is the genuswith the highest number of O-antigen gene clusters. M. oculihas six clusters, M. flava, M. umbonata and M. violaceinigrapossess only four and others contain five clusters .We observed some patterns in gene clusters between species.All Massilia species carry the gmd_rmd_wbaX_wbaY(in exact order) cluster. Only in M. oculi and M. timonaerfbBDAC genes (order in cluster) are presented as an independentcluster. In other genomes, these genes are surroundedby various O-antigen related genes. The same clusterwith rfbBACD (order in cluster) genes and manB occurs inM. violaceinigra, M. plicata, M. flava, M. armeniaca andM. albidiflava. A single gene unrelated to O-antigen productionis DNA-binding protein gene hns.To add more similarity between M. oculi and M. timonae,they possess identical clusters consisting of wbrW, wbdH,wbqB, ugd on the one end and wzx on the other end. Geneslocated among them partake in infection initiation (espH),amino acid biosynthesis (asnB1), acyl-CoA and fatty acidsbiosynthesis ( fadD).In all assemblies, we observed wzm and wzt genes. Mostof the species contain these genes in the order wzm, wzt,unannotated gene and wbaX. The group with such a setincludes M. albidiflava, M. armeniaca, M. oculi, M. putida,M. plicata, and M. timonae. Another gene context is larger,the cluster is flanked by wzm/wzt and vioA. Between them aretwo glycosyltransferase genes wbaX with different lengths,unannotated genes and gtrB. The latter is a viral gene, andit can actually modify O-antigen structure. However, it wasnot described for the E. coli OPS gene cluster. Finally, inM. violaceinigra we found a unique set (not O-antigen biosynthesisgene cluster by our definition) of OPS processinggenes and wbaX. There are three unannotated genes andtwo wzt. For the one beside wzm we didn\u2019t verify a specificdomain, it was indicated as a gene not involved in O-antigensynthesis. The domain structure for wzt laying further fromwzt was proved.One of M. armeniaca clusters contains a full cluster describedfor M. plicata. It starts with mnaA, proceeds with wbrWand three copies of wbdH. In the former species, wzx withunannotated genes is added after the third wbdH. M. umbonatashares the most part of this cluster with M. armeniaca, exceptit lacks mnaA at the beginning. All genomes except M. plicatainclude the galE, hddC and manC part in the exact order inone cluster per genomeConsidering O-antigen ligase gene rfaL, in M. albidiflava,M. oculi, M. plicata, M. timonae and M. violaceinigra thisgene is located next to wbaS. The rest of the species containrfaL outside O-antigen clustersIt can be noticed that some genes, for instance, wbaS, rfbAand rfbB, mnaA, wbdH, are presented in two or more copiesin genomes.Oxalicibacterium. Three clusters were identified for eachspecies of the Oxalicibacterium genus. They share a clusterflanked by wfaK and manC. Their content slightly divergesfrom each other. O. flavum has more genes, including an additionalO-antigen related gene ugd. The OPS ligase gene rfaLwas identified in both assemblies, however, they are locatedin different contexts.Oppositely to O. flavum, O. faecigallinarum carries UDPN-Acetylglucosamine pathway genes . On top of it, in the O. faecigallinarum we could locateduplications of the rfbABCD part, lying in discrete clustersand ordered in a different manner. However, rfbD gene in thebigger cluster is rather dubious, the smaller length comparedto other rfbD instances adds more uncertainty. We did not findthis gene using Orthofinder analysis, although there is a Pfamdomain corresponding to typical rfbD (RmlD_sub_bind) andit was annotated as rfbD by EggNOG.We could detect wzt/wzm genes only in O. flavum assembly.The second species probably either does not carry thesegenes or they can be located outside clusters in unread spacesbetween contigsOxalobacter. For O. formigenes we identified a singleOPS cluster carrying dTDP-sugar pathway genes rfbABCDand vioA and UDP-glucose synthesis gene galE. The rest ofthe genes in the cluster are involved in nucleotide metabolismand cofactor synthesis. Also, any O-antigen processinggenes were undiscovered. We couldn\u2019t detect rfaL gene inthe given assembly. Moreover, even NCBI databases don\u2019thave any information considering this gene or protein in theOxalobacter genusUndibacterium. For U. parvum two clusters were identified,wzt and wzm genes, were located outside them. Interestingly,wzt gene is smaller in comparison to this gene\u2019s length in otherOxalobacteraceae species. Typical of them, wzt is longer thanwzm by approximately 400 bp. In contrast, U. parvum\u2019s wzt isalmost the same size as wzm. Using Pfam service, the gene\u2019sdomain (ABC_tran) was verified.Both clusters possess transferase and nucleotide sugargenes. Most spaces between OPS synthesis genes are unannotatedgenes, except dyp (peroxidase) and ansA (asparaginase)genes. The cluster carrying rfbABCD genes has a copy ofmanC gene and two wbaX genes, which have different sizes.Phylogenetic treeThe phylogenetic dendrogram based on 16S rRNA showedthat the chosen species clustered together considering theirgenera . There had been no study including all speciesand their exact strains used in the current work. Therefore,we could compare only some clades of the tree. Similar toother studies, the first species to branch off is Oxalobacterspecies. Contrary to literature reports, our tree has a distinctOxalicibacterium group and Collimonas with the rest of thespecies of the Oxalobacteraceae family .However, the bootstrap support is rather small at this node.The Janthinobacterium group formation coincided with otherpapers . Some Massilia species clusteredaccording to literature .Also, we obtained an unresolved node between M. armeniacaand M. plicata. The gene lengths used in the analysis variedbetween 1400 and 1500 bp for most cases .In this work, we determined candidate genes involved inO- antigen biosynthesis in bacteria from the Oxalobacteraceaefamily. In comparison to well-studied E. coli O-antigen genes,they are presented in the form of several clusters. A similarsituation has already been described for non-model bacteria. These clusters are dispersed across thegenome. Clusters include O-antigen genes together with additionalgenes, which are necessary for LPS biosynthesis or partake in other processes. The E. coli O-antigen gene clusterwas studied by traditional laboratory methods, in particular,by PCR . These methodsaim to detect specific genes, whereas in silico methodstake into account the gene environment. In other words, theyallow structures to be studied at the cluster level. Thus, ourapproach helps to expand understanding of the O-antigengenetic composition in bacterial genomesDuring OPS genetic structure comparison, we identifiedcommon features presented in all species inside the Oxalobacteraceaefamily. In particular, the group of rfbABCD genes wasdetected in each bacterium. The order of these genes varies,however, they are always placed together in one cluster. Noone gene has deletions, nonsense mutations and other sequenceabnormalities. According to the results, the studied bacteriashould have a correct dTDP-rhamnose synthesis.More similarities were found within each genus. Thesesimilarities relate mainly to individual genes or pairs of genes.A possible explanation lies in the high level of variability ofO-antigens and the rate of bacterial mutations. O-antigensundergo changes so frequently that most of the similaritiesoccur at the species or lower levels rather than at the genusor family level .In 13 bacteria species, wzm and wzt genes were detected.We consider the Wzm-Wzt transporters pathway as the mainpath of O-antigen biosynthesis in this case .Wzx-Wzy pathway was not confirmed due to the absence ofwzy genes.Another interesting finding concerns gene duplication. Themost repetitive genes were identified in Massilia species . Its O-antigens clusters may contain up to three copiesof the same gene. We suggest two possible explanations. Thefirst one is related to the biological features of LPS. The samegene can provide the synthesis of several parts of LPS. Theappearance of additional gene copies can increase the amountof protein in the cell or maintain its level in case one of thegene copies is broken. The second explanation is linked withan algorithm of O-antigen genes search. In our approach,genes are detected according to the principle of homology,so similar genes can be assigned the same name.Symbiotic bacteria Oxalobacter formigenes lacks O-antigenligase gene (waaL) in O-antigen clusters, which may indicatethe absence of O-antigen. The lack of the mentioned structurewas discussed by J.K. Kim et al. (2016) for Burkholderiabacteria species. With our results, we confirm the possibilityof loss of O-antigen genes in symbiotic bacterial species.Overall, the findings of this study indicate differences of nonmodelbacteria from the model one by the example of theOxalobacteraceae family. We suggest that the characterizedOPS gene cluster composition is atypical. So far, most papers,which explored these genes for other bacteria, described onlya single gene cluster. The O-antigen genetics of non-modelbacteria is highly diverse, which is proved by the bioinformaticapproach. The search for homologous sequences allowsus to expand and deepen our understanding of gene clustersinvolved in O-antigen biosynthesis. Further investigation ofthe Oxalobacteraceae O-antigen genetic composition can beconfirmed by laboratory methods.The authors declare no conflict of interest.Baldani J.I., Rouws L., Cruz L.M., Olivares F.L., Schmid M., HartmannA. The family Oxalobacteraceae. In: Rosenberg E.,DeLongE.F., Lory S., Stackebrandt E., Thompson F. (Eds.). TheProkaryotes. Berlin; Heidelberg: Springer, 2014;919-974. DOI10.1007/978-3-642-30197-1_291.Bazhenova A., Gao F., Bolgiano B., Harding S.E. Glycoconjugate vaccinesagainst Salmonella enterica serovars and Shigella species:existing and emerging methods for their analysis. Biophys. Rev.2021;13(2):221-246. 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J.H.S. performed the experiments and wrote the main manuscript text.\u201dnow reads:\u201cAll authors reviewed and approved the manuscript. All authors made significant contributions to the manuscript. K.G.K., Y.J.K., G.T.Y. designed and supervised the research. W.S.K., T.S.J. provided data and guidance for research. J.H.S. performed the experiments and wrote the main manuscript text. J.H.S and W.S.K made equal contributions to the manuscript.\u201dFurthermore, the Acknowledgements section in the original version of this Article was incomplete.\u201cThis work was supported by the GRRC program of Gyeonggi province. [GRRC-Gachon2020(B01), AI-based Medical Image Analysis, and by the Gachon University (GCU-202205980001).\u201dnow reads:\u201cThis work was supported by the GRRC program of Gyeonggi province. [GRRC-Gachon2020(B01), AI-based Medical Image Analysis, and by the Gachon University (GCU-202205980001) and by the MSIT (Ministry of Science and ICT), Korea, under the ITRC (Information Technology Research Center) support program (IITP-2022-2017-0-01630) supervised by the IITP (Institute for Information & communications Technology Promotion).\u201dThe original Article has been corrected."} +{"text": "This corrects the article on p. 927 in vol. 15, PMID: 36188645. In the original publication , two aut"} +{"text": "Correction to: Journal of Neuro-Oncology 10.1007/s11060-022-04223-0In the initial online publication, the name of author Amir H. Zamanipoor Najafabadi was incorrectly specified as Amir. H.Z. Najafabadi. The original article has been corrected."} +{"text": "These sequences frequently mutate, changing the amount of repetitions. SSRs are frequently found in promoters, untranslated regions, and even coding sequences, therefore these alterations can significantly affect practically every aspect of gene activity. SSR alleles can also contribute to normal diversity in brain and behavioural features. Mutational expansion of certain triplet repeats is the cause of a number of inherited neurodegenerative diseases. Due to its importance in genetic research, in this paper we explored Ten SSR markers TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA that are identified from the genomes of Eleven distinct monkeys: A.Nancymaae, C.C.Imitator, C.Atys, M.Leucophaeus, P.Paniscus, R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatus and M.Nemestrina using pattern matching mechanism. We identified 4bp SSR from eleven monkey dataset's Unchr chromosome mainly in this paper. The proposed approach finds the exact place/location of the SSR's and number of times that it appears in the given genome sequence. The identified patterns are analyzed with One-way and Two-way ANOVA that gives better analysis which is useful for genomic studies. Also, this 4bp Ten SSR markers data is a valuable to illustrate genetic variation of genomic study. Specifications TableTandems of repeating DNA sequences are present in various quantities for the majority of genomes in simple sequence repeats (SSRs). This repetition of genetic mapping and population research has been widely employed. SSRs also give molecular tools for the understanding of spatial links between segments of chromosomes which, in turn, help in the analysis of temporal linkages between species and genera.It is predicted that the study of repeat frequency and their distribution pattern in the genome would assist to comprehend their meaning. There are accumulated indications suggesting SSRs influence gene expression Complete genome sequences were available for several species and genome-wide analysis were carried out. In this study, we analysed Unchr chromosome of Eleven different monkeys A.Nancymaae, C.C.Imitator, C.Atys, M.Leucophaeus, P. Paniscus, R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatus and M.Nemestrina and Ten SSR loci were investigated for their spread and frequency of occurrence.Previously, few studies have tried to evaluate tandem replacement distributions in monkey genomes The proposed structure of the method is shown in Fasta format of A.Nancymaae, C.C.Imitator, C.Atys, M.Leucophaeus, P. Paniscus, R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatusand M.Nemestrina datasets are collected and Ten patterns are considered for reading.In this paper Unchr chromosome of A.Nancymaae, C.C.Imitator, C.Atys, M.Leucophaeus, P. Paniscus, R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatus and M.Nemestrina and the ten SSRs are considered. Using a string matching method, SSRs are retrieved from monkeys. String matching is a search method that looks for repeats in a certain chromosome file.first_occurance_position_heuristic, bad_character_heuristic, and good_suffix_heuristic procedures. Finally, this algorithm displays the pattern and its position and continues the search process until the end of the given chromosome sequence.This procedure is repeated for all SSRs as well as the whole data in the chromosomes.The analysis of variance (ANOVA) Within-group variability is measured by how far each sample's value deviates from the sample mean.It assesses the means of two or more samples significance. Their value is less then sample means are close to each other. We can not rule out the null hypothesis in such instance. It is calculated with https://www.ncbi.nlm.nih.gov) provides the genome dataset. The results suggest that SSR identification with pattern matching was quite beneficial in revealing variation in chosen genome libraries. These SSR markers may be used to compare and quantify genomic similarities.A.Nancymaae, C.C.Imitator, C.Atys, M.Leucophaeus, P. Paniscus, R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatus and M.Nemestrina) are taken into account for the identification of the 10 SSR markers listed in Unchr chromosome of monkeys(This method was employed to compare the averages of two or more samples (using the F distribution). This is only applicable to numerical response data (the \"Y\"), which is generally one variable, and numerical or (mostly) categorical input data (the \"X\"), which is always one variable, hence \"One-way\". One-way analysis of variance is performed among A.Nancymaae, C.C.Imitator, Cercocebus_atys, M.Leucophaeus, P. Paniscus,R.Bieti, R.Roxellana, S.Boliviensis, T.Syrichta, C.A.Palliatus and M.Nemestrina for Ten patterns. The actual results are shown in p value, we conclude that there is a similarity of C.Atys monkey with others. The statistic of One-way ANOVA of different chromosomes was depicted as the bar plot, which has been shown in From p value, we conclude that there is a similarity of TCAT,GAAT,CTTT,TCTG with others. The statistic of One-way ANOVA of different patterns was depicted as the bar plot, which has been shown in From It looks at the impact of two categorical independent variables on a continuous dependent variable. It is used to determine not only the main impact of each independent variable, but also whether they interact. It is performed for each of 11 datasets among groups between the ten patterns.The actual results are uploaded in mendeley p value of 11 datasets for ten patterns. These results are shown the relation among monkey datasets interms of supporting the null hypothesis and other are alternate hypothesis. For example from the statistics and p value, it is observed that relation between TAGA and AGAA has alternative hypothesis, and TCTA and GAAT has null hypothesis.Table A.1 to A.11 has shown the Two way ANOVA statistic and Table A.12 to A.21 has shown the Two way ANOVA hypothesis reject TRUE/FALSE for 10 patterns of 11 datasets respectively. These results had shown that relation among patterns. For example relation AGAA b/w CTTT =>FALSE that means hypothesis reject False and for AGA b/w AGAT =>TRUE that means hypothesis reject Truep value of individual ten patterns for 11 datasets. From table Table B.1 for TAGA pattern, it is observed that A.Nancymaae and C.C.Imitator has alternative hypothesis based its statistics and p value and A.Nancymaae and C.Atys has null hypothesis.Table B.1 to B.11 has shown the Two way ANOVA statistic and Table B.12 to B.21 has shown the two way ANOVA hypothesis reject TRUE/FALSE among 11 datasets related to ten patterns respectively. From table Table B.12 for TCAT pattern, it is observed that the relation between A.Nancymaae and C.C.Imitator =>TRUE that means hypothesis reject True and for C.C.Imitator b/w S.Boliviensis=>FALSE that means hypothesis reject False.This work has never been published or submitted to another journal. This information and analysis will not hurt humans or animals.Chinta Someswara Rao: Conceptualization, Methodology, Software, Writing \u2013 review & editing. G.N.V.G. Sirisha: Data curation, Writing \u2013 original draft. K. Butchi Raju: Visualization, Investigation. N V Ganapathi Raju: Supervision, Validation.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."} +{"text": "Scientific Reports 10.1038/s41598-022-09958-4, published online 19 April 2022Correction to: T.V. Sekher was omitted from the author list in the original version of this Article.The Author Contributions section now reads:The concept was drafted by T.M. and S.S.; S.S. contributed to the analysis design, T.V.S. advised on the paper and assisted in paper conceptualization. T.M., S.S., B.H., R.P. and T.V.S. contributed to the comprehensive writing of the article. All authors read and approved the final manuscript.The original Article has been corrected."} +{"text": "The authors of this paper have agrThe updated authorship is listed as below:Donatella Marazziti, Beatrice Buccianelli, Stefania Palermo, Elisabetta Parra, Alessandro Arone, Maria Francesca Beatino, Lucia Massa, Barbara Carpita, Filippo M. Barberi, Federico Mucci and Liliana Dell\u2019Osso. The updated author contribution is as follows:Author Contributions: D.M., B.B., S.P., E.P., L.M., L.D. and F.M. planned the review study. D.M., F.M., B.C., F.M.B., A.A., M.F.B. and L.D. revised all the specific literature. D.M., S.P., E.P. and L.M. wrote the first version of the paper, which was subsequently revised and approved by all authors. All authors have read and agreed to the published version of the manuscript.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated."} +{"text": "Bromus, with focus on Bromus sect. Bromus, we analyzed DNA sequences from two nuclear ribosomal and two plastid regions. We sampled 103 ingroup accessions representing 26 taxa of B. section Bromus and 15 species of other Bromus sections. Our analyses confirm the monophyly of Bromus s.l. and identify incongruence between nuclear ribosomal and plastid data partitions for relationships within and among major Bromus lineages. Results support classification of B. pumilio and B. gracillimus within B. sect. Boissiera and B. sect. Nevskiella, respectively. These species are sister groups and are closely related to B. densus (B. sect. Mexibromus) in nrDNA trees and Bromus sect. Ceratochloa in plastid trees. Bromus sect. Bromopsis is paraphyletic. In nrDNA trees, species of Bromus sects. Bromopsis, Ceratochloa, Neobromus, and Genea plus B. rechingeri of B. sect. Bromus form a clade, in which B. tomentellus is sister to a B. sect. Genea\u2013B. rechingeri clade. In the plastid trees, by contrast, B. sect. Bromopsis species except B. tomentosus form a clade, and B. tomentosus is sister to a clade comprising B. sect. Bromus and B. sect. Genea species. Affinities of B. gedrosianus, B. pulchellus, and B. rechingeri (members of the B. pectinatus complex), as well as B. oxyodon and B. sewerzowii, are discordant between nrDNA and plastid trees. We infer these species may have obtained their plastomes via chloroplast capture from species of B. sect. Bromus and B. sect. Genea. Within B. sect. Bromus, B. alopecuros subsp. caroli-henrici, a clade comprising B. hordeaceus and B. interruptus, and B. scoparius are successive sister groups to the rest of the section in the nrDNA phylogeny. Most relationships among the remaining species of B. sect. Bromus are unresolved in the nrDNA and plastid trees. Given these results, we infer that most B. sect. Bromus species likely diversified relatively recently. None of the subdivisional taxa proposed for Bromus sect. Bromus over the last century correspond to natural groups identified in our phylogenetic analyses except for a group including B. hordeaceus and B. interruptus.To investigate phylogenetic relationships among and within major lineages of Bromus L. is a genus of annual, biennial, and perennial grasses, with 160 to 170 species widely distributed in temperate regions P.M.Sm., B. sect. Bromus, B. sect. Bromopsis Dumort. (syn. B. sect. Pnigma Dumort.), B. sect. Ceratochloa (P.Beauv.) Griseb., B. sect. Genea Dumort., B. sect. Mexibromus Saarela, P.M.Peterson & Vald\u00e9s-Reyna, B. sect. Neobromus (Shear) Hitchc., B. sect. Nevskiella (V.I.Krecz. & Vved.) Tournay, B. sect. Penicillus Llamas & Acedo, B. sect. Sinobromus Keng f., and B. sect. Triniusia (Steud.) Nevski Hack., B. subg. Festucaria Roth, B. subg. Neobromus Shear, B. subg. Nevskiella (V.I.Krecz. & Vved.) V.I.Krecz. & Vved., B. subg. Stenobromus (Griseb.) Hack, and B. subg. Triniusia (Steud.) P\u00e8nzes, nom. illeg. Fourr., Bromus, Ceratochloa P.Beauv., Nevskiella V.I.Krecz. & Vved., Trisetobromus Nevski, and Triniusa Steud. and B. sect. Genea are monophyletic in nrDNA trees but not in plastid trees awns awns . Speciesotential . Based oB. sect. Bromus and is mostly restricted to the tetraploid level (2n = 4x = 28) (n = 3x = 21) and octoploids (2n = 8x = 56) have been recorded , althougrecorded . Data frrecorded , serologrecorded , isozymerecorded , and DNArecorded indicatend Genea .Bromus pectinatus complex comprises annual tetraploid species ranging from southern Africa to Tibet. B. pectinatus, B. pulchellus Fig. & De Not. T\u00e4ckh.), B. rechingeri Melderis, B. gedrosianus P\u00e9nzes, B. tibetanus H.Scholz, and B. pseudojaponicus H.Scholz. More recently, B. gedrosianus, B. pectinatus, B. pulchellus, and B. tibetanus. They treated the names B. rechingeri and B. pseudojaponicus as synonyms of B. pulchellus. Researchers classify species of the B. pectinatus complex in B. sect. Bromus, although they have morphological similarities with B. sect. Genea, such as cuneiform spikelets and B. tectorum L. . Isozyme variation patterns in B. pectinatus, B. japonicus, and B. tectorum support the idea that B. pectinatus may have arisen from hybridization between B. japonicus and B. tectorum P.M.Sm., B. interruptus (Hack.) Druce\u2013B. hordeaceus L., and B. scoparius L.\u2013B. alopecuros Poir. subsp. alopecuros were successive sister groups to the rest of the section, and relationships among the remaining taxa were mostly poorly supported. Bromus using data from ITS and two plastid regions. Although they included few B. sect. Bromus species, they found B. danthoniae Trin. ex C.A.Mey., which many authors have classified in B. sect. Triniusia, to be nested within B. sect. Bromus. Additionally, they found that affinities of B. sects. Bromus and Genea differed between plastid and nrDNA trees. In their nrDNA trees, B. sect. Bromus and B. sect. Genea were monophyletic and not closely related, whereas in their plastid trees, species of these sections formed a clade and neither section was monophyletic. B. sect. Genea polyploids and included multiple B. sect. Bromus species in their analyses. Based on plastid data, they found B. sect. Bromus to be monophyletic in parsimony and maximum likelihood analyses and B. sect. Genea to be monophyletic in parsimony analyses. Based on ITS data, they found B. sect. Bromus and B. sect. Genea to be monophyletic. In their Waxy trees, neither B. sect. Genea nor B. sect. Bromus was monophyletic, as species of both sections were mixed in a clade. These previous studies represented B. sect. Bromus by few species and few molecular markers. Researchers have not studied the phylogeny of B. sect. Bromus with extensive taxon sampling, multiple individuals per taxon, and more than three DNA regions. Furthermore, researchers have not assessed subdivisional classifications of B. sect. Bromus reconstruct phylogenetic relationships among major Bromus lineages; (2) characterize the phylogenetic affinities of the B. pectinatus complex; (3) reconstruct phylogenetic relationships among species within B. sect. Bromus; and (4) assess existing subdivisional classifications of B. sect. Bromus in a phylogenetic context.We aimed to reconstruct phylogenetic relationships among and within major lineages of B. section Bromus and 16 (15 species) from other Bromus sections, in the phylogenetic analyses. We obtained tissue samples from morphological vouchers deposited in herbaria at the Research Institute of Forests and Rangelands, Tehran, Iran (TARI), the University of Tabriz (HCAT), Tabriz, Iran, the University of Isfahan, Isfahan, Iran (HUI), the Canadian Museum of Nature, Ottawa, Canada (CAN), Naturhistorisches Museum Wien, Austria, Vienna (W), the University of Helsinki, Helsinki, Finland (H), and Tarbiat Modares University Herbarium, Tehran, Iran (TMUH), or from fresh material collected in 2016 in Iran by A. Nasiri and colleagues. AN and JMS determined or confirmed the identities of most specimens sampled, and Bromus expert R. Naderi had determined a subset of the specimens from Iran we sampled from ed e.g., . We alsovia gel electrophoresis in 1.25% agarose gels stained with ethidium bromide.We extracted DNA at Tarbiat Modares University and the Canadian Museum of Nature. At Tarbiat Modares University, genomic DNA was extracted from fresh or dried material, mostly using Plant DNA kits following the manufacturer\u2019s instructions or using a modified cetyltrimethylammonium bromide (CTAB) method . At the rpl32-trnLUAG and matK). We amplified ITS, ETS, and matK at Tarbiat Modares University using the following primer pairs and reaction conditions: ITS\u2014primers ITS5m for Sanger sequencing by Macrogen using an Applied Biosystems Prism 3730xl DNA Analyzer .We amplified two nrDNA regions and two plastid regions . We amplified the rpl32-trnLUAG region at the Canadian Museum of Nature using primers rpl32-F and trnL(UAG) , and 1 \u03bcL of DNA template (1:10 dilution) at 98 \u00b0C for 30 s, 34 cycles of 98 \u00b0C for 10 s, 56 \u00b0C for 30 s, 72 \u00b0C for 30 s, and a final extension step of 72 \u00b0C for 5 min; (2) 15 \u03bcL volume with 11.3 \u03bcL of ddH20, 1.5 \u03bcL of 10X reaction buffer, 0.3 \u03bcL of 10 mM dNTP, 0.375 \u03bcL of 10 \u03bcM each primer, 0.75 U of DreamTaq DNA Polymerase , and 1 \u03bcL of DNA template (1:10 dilution) at 95 \u00b0C for 3 min, 35 cycles of 95 \u00b0C for 30 s, 55 \u00b0C for 30 s, 72 \u00b0C for 1.5 min, and a final extension step of 72 \u00b0C for 10 min. Amplification success was assessed via gel electrophoresis in 1.25% agarose gels stained with ethidium bromide.We amplified some samples at the Canadian Museum of Nature. For ITS, ETS, and were KRC , ITS-p5 were KRC , and 26Swere KRC . For matatK_po1F and a nernL(UAG) . We used2O, 1.8 \u03bcL of 5X reaction buffer, 0.5 \u03bcL of primer, 0.5 \u03bcL of BigDye Terminator v3.1 Ready Reaction Mix , and 1 \u03bcL of diluted PCR product. The reaction program consisted of 95 \u00b0C for 3 min, 30 cycles of 96 \u00b0C for 30 s, 50 \u00b0C for 20 s, and 60 \u00b0C for 4 min. We purified reaction products via an EDTA-NaOH-ethanol precipitation protocol recommended by the sequencing kit manufacturer. Purified DNA pellets were resuspended in Hi-Di Formamide, denatured at 95 \u00b0C for 5 min, cooled for 2 min, and sequenced via automated capillary electrophoresis on an Applied Biosystems 3500xL Genetic Analyzer .Sequencing reactions at the Canadian Museum of Nature were performed in 10 \u03bcL reactions containing 6.2 \u03bcL of DNA-grade Hhttps://www.geneious.com, Sequences were assembled, trimmed, and visually assessed using Geneious 11.1.5 software , we defined each codon position and the two non-coding regions as separate data blocks. Incongruence between the combined datasets was statistically evaluated using the incongruence length difference (ILD) test and for the two combined datasets . Each region and each codon position, in the case of protein-coding genes, was treated as a separate partition. For LD) test , implemeLD) test with 1,0http://iqtree.cibiv.univie.ac.at. The models for ML analyses were selected using Model Finder (We performed maximum parsimony (MP) analyses in PAUP* for the combined nuclear and chloroplast DNA datasets, with 1,000 random replications in the heuristic searches, using tree bisection-reconnection branch swapping and 100 random addition sequence replicates. Branch support values were estimated using full heuristic searches with 1,000 bootstrap replicates, each with simple sequence addition and one tree held per replicate. We performed maximum likelihood (ML) analyses using W-IQ-TREE , availabl Finder implemenl Finder and the http://www.phylo.org/; 7 generations, sampling the chains every 1,000th generation. We discarded the first 25% of trees from each run as burn-in and stopped each analysis after the standard deviation of split frequencies dropped below 0.01. The resulting trace files were checked using Tracer v.1.7.1 (Bayesian inference (BI) analyses for single regions and the two combined datasets were performed in MrBayes v.3.2.7a at the C v.1.7.1 to ensur v.1.7.1 .rpl32-trnLUAG, and 91 matK. ITS and ETS alignments consisted of 928 sites for 124 taxa and 1,139 sites for 116 taxa, respectively, of which 214 (23.1%) and 398 (34.9%) sites were variable and 177 (19.1%) and 284 (24.9%) sites were potentially parsimony informative. The mean G + C content of ITS and ETS regions was 56.6% and 53.5%, respectively. The BI cladograms obtained in nuclear ITS and ETS analyses are presented under We produced 383 new sequences from 104 samples: 96 ITS, 93 ETS, 103 rpl32-trnLUAG and matK sequences produced a matrix of 1,065 sites for 110 taxa and 1,443 sites for 111 taxa, respectively. For rpl32-trnLUAG, 127 (11.9%) sites were variable and 95 (8.9%) were potentially parsimony informative. For matK, 133 (9.2%) sites were variable and 103 (7.1%) were potentially parsimony informative. The mean G + C content of the rpl32-trnLUAG and matK regions was 26.4% and 33.3%, respectively. The BI cladograms, along with the bootstrap support values from the ML analyses, for rpl32-trnLUAG and matK data are presented in the The aligned Bromus sections better than the plastid data, and relationships among most species of B. sect. Bromus are unresolved in both nuclear and plastid trees. All plastid trees have higher consistency indices (CI) and retention indices (RI) compared with nrDNA trees. These two indices are also higher in the combined plastid data than the combined nuclear data . These data indicate more homoplasy in the nuclear data than in the plastid data.The nrDNA data resolves relationships among P value of <0.01. Therefore, we did not combine the nuclear and plastid datasets. We interpreted MP bootstrap support (PB) and ML bootstrap support (LB) values of 90\u2013100% as strong support, 70\u201389% as moderate, and 50\u201369% as weak, and we interpreted Bayesian posterior probabilities (PP) \u22650.95 as strong support.The phylogenies derived from the combined nuclear data and the combined plastid data were topologically incongruent, and the ILD test for these two data partitions had a The combined nuclear dataset was 2,067 bp and included 125 taxa, with 1,606 potentially parsimony informative characters and a mean G + C content of 55.1%. Maximum parsimony, maximum likelihood, and Bayesian inference analyses of the combined nuclear matrix produced similar topologies, but the BI tree is better resolved and supported than the other trees. The BI tree, including the support values from the ML and MP analyses for shared clades, is shown in Bromus s.l. is monophyletic with strong support . The genus is divided into two major clades. One clade is weakly supported and comprises B. densus (B. sect. Mexibromus), B. pumilio (B. sect. Boissiera), and B. gracillimus (B. sect. Nevskiella). Bromus pumilio and B. gracillimus are sister taxa . The other clade is strongly supported and comprises two subclades. One subclade comprises all species of B. sects. Bromopsis, Ceratochloa, Genea, and Neobromus and one species of B. sect. Bromus . Bromus section Bromopsis is not monophyletic. Within this subclade, B. ramosus Huds. and B. vulgaris (Hook.) Shear\u2013B. kalmii A.Gray form a weakly to strongly supported clade sister to a maximally supported clade comprising the remaining species. Within the latter clade, B. sect. Ceratochloa species form a strongly supported subclade sister to B. berteroanus (B. sect. Neobromus) . Bromus rechingeri and all B. sect. Genea species form a strongly supported clade . Within this clade, B. rechingeri, B. sterilis, and B. diandrus\u2013B. rigidus Roth form a maximally supported subclade, but relationships among these three lineages are unresolved. Bromus tomentellus (B. sect. Bromopsis) is weakly to strongly supported as sister to the B. sect. Genea\u2013B. rechingeri clade, and these lineages are part of a broader weakly to strongly supported clade including five other B. sect. Bromopsis species .In the phylogenetic trees derived from nrDNA sequences, Bromus sect. Bromus clade) is weakly to moderately supported . It comprises all B. sect. Bromus species except B. rechingeri. Within this clade, B. alopecuros subsp. caroli-henrici is sister to the remaining samples of the clade, which form a maximally supported clade, Bromus sect. Bromus clade A. Within Bromus sect. Bromus clade A, B. hordeaceus and B. interruptus form a strongly supported clade sister to a strongly supported clade, Bromus sect. Bromus clade B , comprising the remaining species. Within Bromus sect. Bromus clade B, a maximally supported subclade comprising B. scoparius is sister to a moderately to strongly supported clade, Bromus sect. Bromus clade C. This clade includes several sublineages; relationships among them are poorly resolved. Bromus briziformis, B. sewerzowii, and B. danthoniae (B. danthoniae var. danthoniae and B. danthoniae var. pauciaristatus) form a strongly supported subclade . The three B. gedrosianus samples form a moderately to strongly supported subclade . The three B. oxyodon samples form a weakly to strongly supported subclade . The three B. pulchellus samples form a moderately to strongly supported subclade . Bromus oxyodon and B. pulchellus from a weakly to strongly supported clade . One sample of B. bromoideus is weakly to strongly supported as sister to the aforementioned lineages.The second subclade a weakly to strongly supported subclade comprising two samples of B. intermedius Guss., three of B. japonicus, one of B. racemosus, two of B. lanceolatus, one of B. squarrosus, two of B. pectinatus, and B. arenarius; (ii) a strongly supported subclade comprising three samples of B. arvensis, one of B. grossus, and one of B. racemosus; (iii) a weakly to strongly supported subclade comprising one B. commutatus sample and two each of B. japonicus and B. racemosus; (iv) a weakly to strongly supported subclade comprising two B. secalinus samples. Multiple individuals of B. racemosus, B. secalinus, B. squarrosus, and B. pseudobrachystachys, one individual of B. arvensis, one of B. bromoideus, and the one sampled individual of B. macrocladus fall along the Bromus sect. Bromus clade C backbone.Of the remaining rpl32-trnLUAG and matK had 2,508 aligned positions and 123 taxa, with a mean G + C content of 30.3%. The BI tree derived from the combined plastid matrix, including the support values from the ML and MP analyses, is shown in Bromus is maximally supported as monophyletic. The genus is divided into two major clades: (i) a strongly supported clade comprising sister groups B. gracillimus and B. pumilio and a moderately to strongly supported subclade corresponding to B. sect. Ceratochloa; (ii) a weakly to moderately supported clade comprising B. densus (B. sect. Mexibromus) and a maximally supported subclade including all species of B. sects. Bromopsis, Genea, and Bromus.The combined matrix of plastid Bromus sect. Bromopsis species except B. tomentosus form a weakly to strongly supported subclade sister to a strongly supported clade including B. tomentosus and species of B. sects. Bromus and Genea, neither of which is monophyletic. Species of B. sect. Bromus and B. sect. Genea form a moderately to strongly supported lineage comprising a five-lineage polytomy: (i) a strongly supported subclade of B. rubens and B. madritensis; (ii) a strongly supported subclade of B. rigidus and B. diandrus; (iii) B. alopecuros subsp. caroli-henrici; (iv) a strongly supported subclade in which B. sterilis is sister to a moderately to strongly supported lineage comprising a three-lineage polytomy: B. tectorum subsp. tectorum, B. rechingeri, and a weakly to moderately supported clade of B. sewerzowii, B. pulchellus, B. oxyodon, and B. gedrosianus; (v) a strongly supported subclade of most B. section Bromus species. Within this last clade, all B. scoparius samples form a weakly supported clade sister to a weakly supported clade comprising the remaining members of B. sect. Bromus, which form a polytomy.B. sect. Bromus species are unresolved, some subclades are present. These subclades include (i) B. squarrosus; (ii) B. pseudobrachystachys; (iii) a strongly supported subclade comprising two B. japonicus samples; (iv) a weakly to strongly supported subclade comprising one B. japonicus sample and one B. intermedius sample; (v) a weakly to strongly supported subclade comprising B. squarrosus and B. hordeaceus; (vi) a moderately supported subclade comprising B. racemosus and B. arvensis; (vii) a weakly supported subclade comprising three B. briziformis samples ; (viii) a moderately to strongly supported subclade comprising one B. interruptus sample sister to a clade of most B. hordeaceus samples; (ix) a weakly to strongly supported subclade comprising samples of B. secalinus, B. racemosus, and B. commutatus sister to a moderately supported subclade comprising four samples of B. commutatus and B. racemosus.Although relationships among most Bromus phylogeny identified previously and provide new insights into relationships among the major Bromus lineages, among species within B. sect. Bromus, and among species of B. sects. Bromus and Genea. Our nrDNA and plastid trees support the monophyly of Bromus s.l., consistent with other phylogenetic studies that sampled the genus broadly Stapp [syn. Boissiera squarrosa (Banks & Sol.) Nevski]; e.g., Bromus, researchers have classified the species in the monotypic B. sect. Boissiera , based on the shared character state of multiple lemma awns, which is absent in other Bromus species (B. sect. Bromus (including B. danthoniae) and B. pumilio arose independently, the presence of multiple lemma awns in B. pumilio and B. danthoniae is homoplasy.2n = 14; , ranges 2n = 14; . It is c2n = 14; . Some reoissiera and in Bus e.g., , 1972. Cus e.g., , our resserology , 1972 anserology also sup species . Our resBromus gracillimus, a diploid (2n = 14), ranges from eastern Turkey to Xinjiang and the Western Himalayas (B. gracillimus in B. sect. Nevskiella (B. subg. Nevskiella (Nevskiella (N. gracillima (Bunge) V.I.Krecz. & Vved.; e.g., B. gracillimus in Bromus, consistent with earlier studies , or a combination of these. Researchers have not previously hypothesized a close relationship among B. pumilio, B. gracillimus, and species now included in B. sect. Mexibromus, nor are we aware of putative morphological synapomorphies for the clade. Study of lemma and palea micromorphological characters in B. sect. Mexibromus species may be insightful, since these characters are distinct in B. pumilio and B. gracillimus compared to the rest of the genus . This topology is consistent with ITS trees in In the plastid trees, studies . In addiNA trees . In the B. sect. Ceratochloa species. Bromus sect. Ceratochloa comprises hexaploids, octoploids, and dodecaploids; diploids or tetraploids are unknown Stebbins, a duodecaploid native to North America with 96 medium-sized chromosomes or a relative of B. berteroanus (B. arizonicus). They hypothesized that these plants, which are morphologically similar to B. ayacuchensis Saarela & P.M.Peterson originated in a common ancestor of B. pumilio and B. gracillimus and became incorporated into ancestral members of the Ceratochloa lineage via introgressive hybridization. The monophyly of B. sect. Ceratochloa in the plastid trees indicates the plastomes of species in the section share a common origin. Accordingly, if the octoploid and duodecaploid members of the section arose via hybridization between members of the hexaploid B. catharticus complex and other Bromus lineages, as researchers have hypothesized, we infer, based on the plastid topology, that individuals of the B. catharticus complex were the maternal parents (plastome donors) in the crossing events. Indeed, if the plastome donor(s) were from Bromus lineages other than B. sect. Ceratochloa, we would not expect B. sect. Ceratochloa to be monophyletic in plastid-based phylogenetic analyses. Given the nrDNA results, we infer that species of B. sect. Bromopsis, their relatives, or their ancestors contributed at least one genome to the B. sect. Ceratochloa\u2013B. sect. Neobromus lineage and the B. sect. Genea\u2013B. rechingeri lineage. We find poor support for relationships among B. induratus, B. sclerophyllus, and B. kopetdagensis, whereas B. tomentellus, a species native to Southwest Asia and the eastern Mediterranean countries, is sister to the B. sect. Genea\u2013B. rechingeri lineage. The close relationship among the Old World species B. ramosus and the North American species B. vulgaris and B. kalmii is consistent with morphological and cytological similarities among B. ramosus and North American B. sect. Bromopsis species identified by y levels . Althoug2n = 42; , B. kope2n = 28; , B. scle 70, 84) , and B. studies . Our nrDB. sect. Bromopsis species except B. tomentosus form a clade in the plastid trees, consistent with previous plastid results is sister to a broad clade including B. sect. Bromopsis (paraphyletic), B. sect. Ceratochloa\u2013B. sect. Neobromus, and a B. sect. Genea\u2013B. rechingeri clade that is nested deep within the broader lineage. This topology is consistent with ITS trees in B. sect. Bromus and B. sect. Genea form a clade, consistent with plastid trees in previous studies (B. sect. Bromus\u2013B. sect. Genea clade comprises a five-lineage polytomy: B. diandrus\u2013B. rigidus (B. sect. Genea), B. madritensis\u2013B. rubens (B. sect. Genea), B. alopecuros subsp. caroli-henrici (B. sect. Bromus), a clade comprising five B. sect. Bromus species and two B. sect. Genea species , and a clade comprising the remaining B. sect. Bromus species.The nrDNA and plastid data are incongruent regarding the affinities of een them . In the studies , and neiB. sect. Bromus species that form a clade with B. sterilis and B. tectorum in the plastid tree but are part of the B. sect. Bromus lineage in the nrDNA trees are members of the B. pectinatus complex, a group defined by B. gedrosianus and B. pulchellus between the nrDNA and plastid trees suggest the possibility of plastid capture from the B. sect. Genea lineage into these species. These results are consistent with the hypothesis that B. pectinatus complex species are derived from hybridization between species of B. sect. Bromus and B. sect. Genea occupies a \u201csomewhat intermediate position\u201d between B. sect. Bromus and B. sect. Genea, indicative of a hybrid origin for the taxon. Previous studies identified the same discordant pattern between nrDNA and plastid data for B. pectinatus\u2014the only B. pectinatus complex species previously included in DNA sequence-based phylogenetic analyses\u2014that we found for B. gedrosianus and B. pulchellus in the plastid trees but are part of the B. sect. Bromus lineage in the nrDNA trees. Accordingly, we infer that B. sewerzowii and B. oxyodon likely obtained their plastomes via plastid capture from the B. sect. Genea lineage, like species of the B. pectinatus complex. Bromus sewerzowii is a tetraploid 3\u20134 mm, panicles open, with nodding branches several times longer than the spikelets, lower glumes ca. 10 mm, lemmas 15\u201318 mm, and awns 20\u201325 mm, lower part slightly flattened, twisted, and recurved in the nrDNA trees provides further support for 2n = 28; that occ2n = 28; . It is c2n = 28; . Bromus pikelets . Despite2n = 28; . It occu2n = 28; . Bromus recurved . Bromus ceolatus , but ourB. rechingeri in the plastid trees are similar to other B. pectinatus complex species, but in the nrDNA trees B. rechingeri falls in the B. sect. Genea clade rather than the B. sect. Bromus clade like the other B. pectinatus complex species. Given this unexpected nrDNA topology, two of us (A. Nasiri and B. Hamzeh\u2019ee) reviewed the B. rechingeri voucher specimen, housed in TARI, to confirm its identification. The specimen bears multiple annotations. It was originally determined as B. japonicus (without identifier name). Later, M. Alemi identified it as \u201cB. gedrosianus (syn. B. rechingeri)\u201d and R. Naderi as Bromus cf. rechingeri. Using the key in the Bromus treatment in Flora Iranica (B. rechingeri. The placement of this sample within the B. sect. Genea lineage in the nrDNA trees may indicate a hybrid origin for the specimen (this could explain why Naderi determined the specimen as B. cf. rechingeri) and, perhaps, the species. In addition, this B. rechingeri sample is distinct from B. pulchellus in the nrDNA and plastid trees; the species are not resolved as sister taxa. These results do not support B. rechingeri as a synonym of B. pulchellus. Given that we sampled only one individual of the taxon, future work should sample multiple individuals of B. rechingeri sensuB. rechingeri var. afghanicus H.Scholz (=B. rechingeri subsp. afghanicus (H.Scholz) H.Scholz; B. rechingeri subsp. rechingeri and B. oxyodon based on its morphology, whereas B. pulchellus.The affinities of Iranica , we idenB. arenarius, a tetraploid native to Australia, may be an intersectional amphidiploid originating from hybridization between B. sect. Bromus and B. sect. Genea species based on chromosomal data derived from crossing experiments and morphology . Additionally, B. arenarius and B. pectinatus are morphologically similar, and some authors have suggested the two may not be distinct species in their ITS trees. Based on their ITS phylogeny, B. arenarius being a hybrid between B. sects. Bromus and Genea. Because data for the two plastid regions sampled in our study was not available for B. arenarius, we were unable to test the hybrid-origin hypothesis for the taxon by comparing nrDNA and plastid topologies that include the taxon. Nevertheless, other plastid data for B. arenarius provide some insight into its likely affinities in plastid-based phylogenies. A rbcL sequence from a B. arenarius accession collected in New Zealand is more similar to rbcL sequences of B. sterilis (B. sect. Genea) than of B. sect. Bromus species, based on a GenBank BLAST search. The rbcL similarity between B. arenarius and B. sect. Genea is consistent with the topology we observed for B. gedrosianus, B. oxyodon, B. pulchellus, B. rechingeri, and B. sewerzowii in our plastid trees. We thus infer that nrDNA and plastid regions in B. arenarius are incongruent, supporting the possibility of an intersectional hybrid origin for the taxon, as first hypothesized over 75 years ago.Researchers have also suggested rphology , 1981. Ses e.g., . We inclB. sect. Genea taxa from which the plastomes of the B. pectinatus complex and allies likely originated. Based on the plastid topology, we infer that B. sterilis comprising all other sampled species of the section. The long branch in the nrDNA tree subtending B. sect. Bromus clade A, which includes all taxa except B. alopecuros subsp. caroli-henrici, indicates considerable molecular evolution in the nrDNA regions since the lineage split from its sister group, B. alopecuros subsp. caroli-henrici, and before the lineage diversified. Similarly, a long branch in the nrDNA tree separates the B. hordeaceus\u2013B. interruptus clade from B. sect. Bromus clade B, indicating considerable genetic differentiation between these lineages, and the B. scoparius clade is subtended by a slightly longer branch compared to its sister lineage, B. sect. Bromus clade C. Within clade C, however, branch lengths are short in the nrDNA tree. This is indicative of little variation in the gene regions we sampled. Indeed, phylogenetic resolution in this clade is poor and only three species are resolved as monophyletic. Aside from the strongly supported three-taxon clade comprising B. briziformis, B. danthoniae, and B. sewerzowii, our nrDNA analyses identify a few clades comprising individuals of multiple species, three of which are strongly supported in Bayesian and maximum likelihood analyses, whereas relationships among most individuals and species in the clade are unresolved . We are unable to make inferences about phylogenetic relationships among most species in the clade due to the lack of resolution. The pattern is similar in the plastid trees, where only B. briziformis and B. pseudobrachystachys are resolved as monophyletic, one clade comprises multiple individuals of several species, and relationships among most individuals and multi-individual lineages are unresolved. Low genetic differentiation in the nrDNA and plastid sequences among most B. sect. Bromus species indicates they are likely relatively young and probably diversified rapidly. Moreover, multiple speciation events may have happened at the same time, and some lineages may be equally closely related to one another, challenging phylogenetic reconstruction. We are unable to distinguish between the hypotheses of rapid radiation or multiple simultaneous speciation events with the current data. Nevertheless, our results are consistent with B. sect. Bromus species likely evolved in response to agricultural conditions, including grazing livestock. Similarly, We identify four main lineages within e.g., B. sect. Bromus species, combining independent genomes, and there were instances of polymorphism in a subset of our nrDNA sequences, which we coded with nucleotide ambiguity codes. Misidentification may also be a factor in some instances, even though we were careful in attempting to ensure all sampled individuals were accurately determined. A limitation of our study is that we did not clone the nrDNA regions we studied to obtain all sequence variants that may be present within closely related individuals and species, many of which are polyploids. Studies of grasses that characterized nrDNA variation within and among individuals of multiple closely related diploid and polyploid species found numerous haplotypes within individuals and species and complicated patterns of nrDNA evolution would benefit from approaches that captures all ribosomal DNA copies within individuals, whether through cloning or next generation sequencing approaches would likely be informative in reconstructing the clade\u2019s evolutionary history, including identifying the parental taxa of the polyploid species. Indeed, such approaches have been successful in resolving relationships among closely related taxa in diverse groups of plants, including grasses in the nrDNA trees, consistent with the ITS tree in Bromus alopecuros subsp. caroli-henrici is similarly distinct from other B. sect. Bromus species in the plastid tree. However, additional plastid genome sampling will be necessary to resolve the polytomy in the plastid tree formed by B. alopecuros subsp. caroli-henrici, the clade comprising most B. sect. Bromus species, and the lineages comprising species of B. sect. Genea and B. pectinatus and allies.B. alopecurosB. alopecuros subsp. caroli-henrici. Bromus alopecuros is native to the central and eastern Mediterranean , spikelets often borne singly at nodes (vs spikelets mostly 2\u20134 at each node), and lemmas with acuminate apical teeth Acedo & Llamas . Like B.2n = 14; . It rang2n = 14; . Smith iB. sect. Bromus clade after B. alopecuros subsp. caroli-henrici is a lineage comprising B. hordeaceus and B. interruptus. In the nrDNA tree, these two species form a strongly supported clade, but neither is monophyletic. In the plastid tree, the sample of B. interruptus from which we obtained data from both plastid regions (accession 1) is sister to a clade comprising all but one B. hordeaceus sample (accession 6). The rpl32-trnL sequences from B. interruptus (accession 1) and the B. hordeaceus samples are identical, whereas the matK sequences in B. interruptus (accession 1) and the B. hordeaceus samples differ by one base. The other B. interruptus sample in the plastid tree, however, is not included in a clade with B. hordeaceus. This sample is represented by a matK sequence with multiple infraspecific taxa; Bromus interruptus, a winter annual grass, is endemic to southern and eastern England and tetraploid on the International Union for Conservation of Nature (IUCN) Red List , to be a hybrid or an introgressive hybridization product of B. lepidus and B. hordeaceus s.l. that arose no more than about 200 years ago. Some authors treat the name B. incisus as a synonym of B. lepidus Barina Barina .B. hordeaceus\u2013B. interruptus and Bromus sect. Bromus clade B, which comprises the remainder of B. sect. Bromus except B. alopecuros subsp. caroli-henrici, is consistent with nrDNA trees in B. hordeaceus may have originated from the crossing of B. arvensis (diploid) and B. scoparius H.Scholz, B. danthoniae subsp. rogersii C.E.Hubb. ex H.Scholz), and he also described B. turcomanicus H.Scholz, a second species of B. sect. Triniusia he knew only from the type locality in Turkmenistan. In a revision of these taxa, B. danthoniae: B. danthoniae var. danthoniae and B. danthoniae var. pauciaristatus. The latter taxon differs from the nominate variety by most lemmas having one awn and upper lemmas of at least one spikelet with multiple awns, or one awn with one or more minute awns.2, or 6) . Because. Bromus . In the studies . Scholz B. danthoniae proposed by B. danthoniae var. danthoniae, B. danthoniae var. pauciaristatus, B. briziformis, and B. sewerzowii form a strongly supported clade. Of these taxa, only B. sewerzowii, for which we sampled two individuals, is recovered as monophyletic. Its affinity with B. briziformis and B. danthoniae based on nrDNA data is a novel result, as the species has not previously been sampled in a molecular phylogenetic analysis. Previous researchers did not consider B. sewerzowii to be closely related to B. briziformis or B. danthoniae and spikelets broadly ovate (vs spikelets ovate or oblongate-lanceolate) . Smith (B. lanceolatus (2n = 28), distributed from the Mediterranean to Xinjiang and Pakistan, and B. danthoniae to be closely related , B. intermedius Hack. (=B. subg. Bromus), circumscribed based on anther length: B. sect. Macrantheri Holmb., with two species, and B. sect. Brachyantheri Holmb., with eleven species. He recognized two subgroups in B. sect. Brachyantheri: B. subsect. Coriacei Holmb., nom. superfl., with five species, and B. subsect. Molles Holmb., with six species. The name B. subsect. Coriacei is superfluous and illegitimate because the subsection as circumscribed by Holmberg includes the type of the genus, B. secalinus.Bromus s.str. and B. subg. Bromus in the 1930s. Bromus s.str.: B. sect. Aphaneuroneuron Nevski, nom. superfl., including the seven taxa Holmberg classified in B. sect. Macrantheri and B. subsect. Coriacei; B. sect. Sapheneuron Nevski, including the six taxa Holmberg classified in B. subsect. Molles plus three additional species; and B. sect. Triniusia (Steud.) Nevski, including B. danthoniae. The name B. sect. Aphaneuroneuron is superfluous and illegitimate because the section includes the type of the genus, B. secalinus. In the same year, B. subg. Zeobromus (=B. subg. Bromus) species in the former Union of Soviet Socialist Republics comprising seven series: B. series Secalini V.I.Krecz. & Vved., nom. superfl., with one species; B. series Macrantherae V.I.Krecz. & Vved., with one species; B. series Squarrosae V.I.Krecz. & Vved., with four species; B. series Commutatae V.I.Krecz. & Vved., with four species; B. series Dolicholepides V.I.Krecz. & Vved., with three species; B. series Ambiguae V.I.Krecz. & Vved., with one species; and B. series Macrostachyae V.I.Krecz. & Vved., with two species. The name B. series Secalini is superfluous because its type, B. secalinus, is the type of the genus. B. subg. Serrafalcus (Parl.) P\u00e9nzes (=B. subg. Bromus) in four groups based on morphology: \u201cB. sect. Arvenses,\u201d with three species; \u201cB. sect. Racemosi,\u201d with three species; \u201cB. sect. Commutati,\u201d with eleven species; and \u201cB. sect. Pectinati,\u201d with seven species. However, Researchers proposed three classifications of Bromus was proposed in the 1960s and three in the 1970s. B. sect. Bromus: B. subsect. Coriacei, nom. superfl.; B. subsect. Triniusia (Steud.) Tournay; and B. subsect. Molles. He did not list the species included in each subsection. B. subg. Bromus: B. sect. Triniusia and B. sect. Bromus, and he subdivided B. sect. Bromus into eight series: B. series Intermediae H.Scholz, with one species; B. series Macrantherae, with two species; B. series Squarrosae, with two species; B. series Molles H.Scholz, with three species; B. series Interruptae H.Scholz, with one species; B. series Racemosae H.Scholz, with two species; B. series Secalinae, nom. superfl. (=B. series Bromus), with three species; and B. series Michelariae H.Scholz, with one species. B. sect. Bromus based on serological evidence of caryopsis proteins and morphological similarity in characters such as lemma shape, lemma texture, panicle shape, and caryopsis size and shape. Using morphological data, he recognized nine groups, designated 1 to 9. Based on the results of his serological experiments, he revised his morphology-based classification slightly and recognized ten groups, designated A to J, each including one to four species. Bromus s.str.: B. sect. Aphaneuroneuron, nom. superfl. (=B. sect. Bromus), with nine species; B. sect. Triniusia, with one species; and B. sect. Sapheneuron, with six species.One subdivisional classification of Bromus s.str./Bromus s.l. subg. Bromus in recent decades. Flora of Russia: The European Part and Bordering Regions, recognized three sections within Bromus s.str.: (1) B. sect. Bromus, with the same species he B. sect. Triniusia, also equivalent to his earlier treatment . B. sect. Macrantheri, B. subsect. Brachyantheri, and B. sect. Squarrosi as synonyms of the name B. sect. Bromus, and he treated the name B. subsect. Molles as a synonym of B. sect. Sapheneuron.Researchers have published classifications of ecies he had prevreatment ; and (3)B. sect. Bromus species remain unresolved in the nrDNA and plastid trees, there is sufficient resolution in our trees to conclude that few previously recognized subdivisional taxa of B. sect. Bromus/B. subg. Bromus correspond to natural groups. This is particularly true for the nrDNA trees, in which several previously recognized taxa are polyphyletic. These include Bromus subsect. Molles sensuB. sect. Sapheneuron sensusensui.e., B. series Commutatae, B. series Dolicholepides, B. series Squarrosae, and B. series Macrostachyae), B. sect. Aphaneuroneuron and B. sect. Sapheneuron sensuBromus groups 7/F, 4/E, and 9/J sensuB. sect. Bromus sensuB. sect. Squarrosi sensuBromus sect. Bromus sensuB. sect. Triniusa. We are unable to assess the monophyly of B. series Macrantherae sensuB. arvensis and B. brachystachys and of B. series Racemosae sensuB. pseudosecalinus.Although many relationships among B. sect. Bromus that corresponds to a monophyletic group in our nrDNA trees is B. hordeaceus and allies and B. interruptus. By contrast, B. hordeaceus and allies (taxa he later recognized as subspecies of B. hordeaceus) in B. series Molles and B. interruptus in B. series Interruptae. Our results do not support inclusion of B. interruptus in a group separate from B. hordeaceus. If we were to recognize the lineage including B. hordeaceus as a subsection or a series, the correct names for the taxon at these ranks are likely B. subsect. Molles and B. series Molles; B. hordeaceus is the type of both names. If, in a classification of the genus treating the major generic lineages as subgenera, we were to recognize the clade including B. hordeaceus and B. interruptus as a section, we would require a new name at that rank.The only previously recognized group within 10.7717/peerj.13884/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.13884/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.13884/supp-3Supplemental Information 3Click here for additional data file.10.7717/peerj.13884/supp-4Supplemental Information 4Click here for additional data file.10.7717/peerj.13884/supp-5Supplemental Information 5Bayesian posterior probabilities and maximum likelihood bootstrap support are indicated above the branches, respectively. Posterior probabilities <0.5 and bootstrap support <50% are indicated with a hyphen.Click here for additional data file.10.7717/peerj.13884/supp-6Supplemental Information 6Bayesian posterior probabilities and maximum likelihood bootstrap support are indicated above the branches.Click here for additional data file.10.7717/peerj.13884/supp-7Supplemental Information 7Bayesian posterior probabilities and maximum likelihood bootstrap support are indicated above the branches.Click here for additional data file.10.7717/peerj.13884/supp-8Supplemental Information 8Bayesian posterior probabilities and maximum likelihood bootstrap support are indicated above the branches.Click here for additional data file.10.7717/peerj.13884/supp-9Supplemental Information 9Numbers above branches are bootstrap values.Click here for additional data file.10.7717/peerj.13884/supp-10Supplemental Information 10Numbers above branches are bootstrap values.Click here for additional data file.10.7717/peerj.13884/supp-11Supplemental Information 11Numbers above branches are bootstrap values.Click here for additional data file.10.7717/peerj.13884/supp-12Supplemental Information 12Numbers above branches are bootstrap values.Click here for additional data file."} +{"text": "Communications Medicine 10.1038/s43856-022-00178-5, published online 12 September 2022.Correction to: An author, Zitta Barrella Harboe (Z.B.H.), had inadvertently been omitted from the author list of this article. This author has now been added and the author list is as follows: \u2018Rebecka Svanberg, Cameron MacPherson, Adrian Zucco, Rudi Agius, Tereza Faitova, Michael Asger Andersen, Caspar da Cunha-Bang, Lars Klingen Gj\u00e6rde, Maria Elizabeth Engel M\u00f8ller, Patrick Terrence Brooks, Birgitte Lindegaard, Adin Sejdic, Zitta Barrella Harboe, Anne Ortved Gang, Ditte Stampe Hersby, Christian Brieghel, Susanne Dam Nielsen, Daria Podlekareva, Annemette Hald, Jakob Thaning Bay, Hanne Marquart, Jens Lundgren, Anne-Mette Lebech, Marie Helleberg, Carsten Utoft Niemann, Sisse Rye Ostrowski\u2019.Z.B.H. is affiliated with the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, Nordsj\u00e6llands Hospital, Hiller\u00f8d, Denmark, and the Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.The \u201cAcknowledgements\u201d section has been updated to include funding received by Z.B.H. and is now as follows: \u2018The authors would like to acknowledge all the investigators and patients participating in this study. This work was supported by a grant from the Ministry of Higher Education and Science, Copenhagen, Denmark (0238-00006B) and was further supported by funding from the Lundbeck Foundation .\u2019The \u201cAuthor contributions\u201d section has been updated to include Z.B.H. and is now as follows: \u2018S.R.O. and C.N. designed and initiated the study and share senior authorship. R.S., A.H., S.D.N. collected the data, and RS analyzed data and wrote the first draft of the manuscript. C.M. contributed with supervision and input for data analysis, discussion, and interpretation of results. A.Z., R.A., T.F., and L.K.G. gave input to data visuization, analysis, and interpretation. L.K.G., M.A.A., C.C.B., C.B., C.N. and S.R.O. contributed to the discussion and clinical interpretation of data and results. S.R.O. was responsible for the TruCulture analysis, and provided the TruCulture data. J.B. and H.M. analyzed and provided the flow cytometry data, and contributed to data interpretation. P.T.B., B.L., A.S., A.O.G., D.S.H., M.M., D.P., Z.B.H. and C.B. helped to include patients in the study and collect clinical data. J.L., A.M.L., and M.H. contributed to management of the study and to the discussion of the results. All authors participated in writing and editing the final manuscript.\u2019These changes have been made in the HTML and PDF versions of the article."} +{"text": "Dear Editor,Ricinus communis was first reported in 2010 [Chrysanthemum nankingense) [Coptis chinensis) [Aristolochia fimbriata [Taxus species [Medicinal plants are composed of complex natural compounds with diverse medicinal applications, which makes them crucial resources for drug research. Since the genome of the medicinal plant inensis) , Aristolimbriata , and Tax species \u20137. Many species . Howeverhttp://www.herbgenome.com/) to collect genomic data on herbal plants and information on natural medicinal ingredients in the pharmacopeia. This database provides resources for traditional medical research. It includes BLAST [We have built the 1\u00a0K Medicinal Plant Genome Database , and then search for gene sequence, structure, and annotation information by gene name in 1\u00a0K-MPGD\u2019s gene function search tool. The JBrowse tool in 1\u00a0K-MPGD shows the location of the gene in the species genome. The one-stop integration of metabolism, gene, and genome datasets provides great convenience for medicinal plant research .L.Y., S.C., and C.S. designed and managed the project; D.W., Z.S., and Y.Y. constructed the database. X.S. and D.W. collected and analyzed the data. X.S., L.Y., D.W., Z.S., Y.Y., S.C., and C.S. participated in discussions. X.S., L.Y., S.C., and C.S. wrote and revised the manuscript.http://www.herbgenome.com/ via the World Wide Web. A reliable data management system has been developed and all newly released information will be updated on this website. Enquiries concerning the database should be directed by email to support@benagen.com.The 1\u00a0K-MPGD can be freely accessed at The authors declare that they have no conflict of interest.sec id=\"sec5\">Supplementary data

Supplementary data is available at Horticulture Research online.

P > Mg \u2265 Mo > Ca > S \u2265 Ni > Zn > Mn > Se > Fe \u2265 Co. The largest proportion of ash residue in raspberry fruits is K. Depending on the cultivar, its quantity averaged from 12.81 wt % (Samorodok and Karamelka) to 22.37 wt % (Atlant). The minimum K content was observed in the ash of the Carolina cultivar (5.62 wt %), while in berries of this cultivar Mg (2.91), Ca (2.62) and Zn (0.14 wt %) accumulated above average. Among the group of early maturing cultivars, the cultivar Yubileinaya Kulikova stands out with a high content of Mo (4.63), Ca (2.19), Fe (0.25) and Co (0.21 wt %). The cultivar Pingvin is characterized by a high content of K (22.65) and Se (0.31 wt %). The medium maturity cultivar Samorodok is characterized by a higher content of P (4.08), S (0.47), Ni (0.51) and Zn (0.26 wt %). Among the late maturing cultivars, the cultivar Poranna Rosa stands out with the preferential accumulation of nine elements: Mg (2.98), P (4.42), S (0.36), K (20.34), Ca (1.71), Mn (0.14), Co (0.13), Se (0.21) and Mo (3.08 wt %). Correlation relationships between the elements have been established. Samples with the highestaccumulation of macro- and microelements in berries represent genetic sources for further selection of raspberry forimprovement of the mineral composition of fruits. Raspberries are one of the most popular berry crops in householdfarms and industrial production. In recent years, raspberryselection has shifted the focus from agronomic characteristicsto characteristics related to sensory qualities of the fruit and potential health benefits . At the same time, significant advances were madein the analytical chemistry of fruits. These new tools generateknowledge that can significantly accelerate the creation of newcultivars that meet consumer expectations in terms of sensoryperception and the health benefits of eating fruit. In recentyears, significant researches have identified environmental,biochemical, and genetic factors underlying the accumulationof certain compounds in raspberry fruits .Raspberries are a source of biologically active compoundsand minerals that have a positive effect on human health. Minerals belong tothe vital components of nutrition (micronutrients) with a widevariety of physiological functions. They play an importantrole in plastic processes, the formation and construction ofbody tissues, in particular, the bones of the skeleton. Mineralsubstances are necessary for maintaining acid-base balance inthe body, creating a certain concentration of hydrogen ions intissues and cells, interstitial and intercellular fluids, as well asgiving them osmotic properties that ensure the normal courseof metabolism. Mineral elements have antioxidant properties,are involved in redox processes, in carbohydrate, protein,vitamin and fat metabolism, in the formation of bone tissue,regulate heat and gas exchange, hematopoiesis, growth, respiration,play an important role in immunobiological reactions,affect water-salt and acid-base balance . For example, Fe, being an indispensable component ofblood, is involved in oxygen transport and oxidative metabolism. Ca is necessary for the formationof bone and connective tissue, is involved in the transmissionof nerve impulses and muscle contraction . Cu is a part of a number of important enzymes,normalizes cellular metabolism and catalyzes some of thereactions necessary for the normal functioning of the brainsand nervous system. Mg is vital for energy metabolism. Mgand Mn are parts of enzymes, are involved in the metabolismof carbohydrates, amino acids and cholesterol . Zn maintains an optimal concentration of tocopherol,plays an important role in the growth and development ofplants, in the formation of the immune response, the functionof the nervous system, promotes the absorption of vitamin A. In the prevention and treatment ofage-related diseases, antioxidant strategies based on nutritionare used, including the addition of antioxidants and trace elementsin the prevention .Significant intervarietal differences in the mineral content ofNa, K, Ca, Mg, Fe, Cu and Zn in raspberry fruits of differentcolors were established by the studies of Akimov et al. (2021).The quantitative and qualitative composition of mineral substancesof fruits and berries depends on the botanical species,cultivar, soil and climatic conditions, methods of cultivation,etc. . Despite the role of micronutrients,they have not received as much attention as vitamins, and thismay be due to the fact that the safety range between deficiencyand toxicity of some trace elements is relatively narrow.Nevertheless, with the spread of knowledge about rationalnutrition and the therapeutic and prophylactic properties offruits and berries among the population, the demand for them,including raspberries, is growing, which is mostly satisfied byrepair cultivars . Despite thepopularity of repair raspberries in industrial production, thereis only fragmentary information about the mineral compositionof its fruits in the scientific literature. Comparative studies ofthe mineral composition of the repair raspberries berries of theFederal Research Center of Horticulture collection have notpreviously been conducted. Consequently, the systematizationof the content of macro- and microelements in the fruits ofrepair raspberry cultivars using modern high-tech analyticalmethods and the typification of samples of the Rubus idaeus L.collection is very relevant.In this regard, the purpose of our work was to determine thecontent of macro- and microelements in the fruits of variouscultivars of repair raspberries using modern high-tech analyticalmethods and to isolate the genetic sources of the analyzedelements for further selection.The research was conducted in 2021 in the Laboratory ofBiochemistry and Physiology of Plants of the Federal StateBudgetary Institution of the Federal Research Center ofHorticulture. The objects of study were the fruits of 17 repaircultivars of raspberries (Rubus idaeus L.) of various ecologicaland geographical origin, differing in terms of ripening,color and other economic and biological signs and properties(Table 1). The raspberries were grown on the site of the geneticcollection of the Kokinsky experimental station of the FederalResearch Center of Horticulture, located , according to the generally accepted technologywith late autumn mowing of stems .The soils were gray forest, well cultivated, medium loamy.The depth of the arable layer was 26 cm, the humus contentwas 3.2 %, \u04202\u041e5 was 35 mg per 100 g of soil, K2\u041e was 13.5 mgper 100 g of soil, the reaction of the soil solution was slightlyacidic (pH 6.1).The scheme of planting on the site was single-row, thedistance between the rows was 3 m, and between the plants it was 0.5 m. During the season, one spring nitrogen fertilizationwas carried out (35 kg/ha a.i.). The intervals of the rows in thefirst half of the growing season were kept under pure steam,and after flowering under natural grassing.A representative sample of mature raspberries with anaverageweight of 200 g was dried in a drying oven at a temperatureof 50\u201360 \u00b0C. The dried samples were mineralizedin a muffle oven Naberterm (Germany) at a temperature of450 \u00b0C in accordance with the Russian State Standard GOST26929-94 (2002). The resulting ash was dispersed by ultrasoundat a frequency of 18 kHz for 15 min. A uniform layer ofdisperse was applied to a stage table covered with carbon tape.The chemical composition of 12 main ash elements \u2013 Mg, P,S, K, Mn, Co, Fe, Ca, Zn, Ni, Se and Mo \u2013 was determined byenergy dispersion spectrometry (EDS) on an analytical scanningelectron microscope JEOL JSM 6090 LA in accordancewith the technique . The resolution of themicroscope was 4 nm, the accelerating voltage was 20 kV(image of secondary electrons). The working distance duringthe elemental analysis was 10 mm. The energy-dispersive microanalysisdata were presented in accordance with standardprotocols and included images of the microstructures of thesample under study, a table of weight data and spectral linesof the diagnosed elements. An example of an analysis reportis shown in Figure 1.The concentration of the desired elements was determinedby the intensity of the spectral lines. The accuracy of chemicalanalysis was determined as follows: at the concentration ofelements from 1 to 5 %, the accuracy was less than 10 %; atthe concentration of elements from 5 to 10 %, the accuracywas less than 5 %; and at the concentration of elements morethan 10 %, the accuracy was less than 2 %. In total, 10 sitesof each sample were examined. The local analysis was 3 mm,and the scanning area was at least 12 \u03bcm.The results were expressed as average values (n = 10) asstandard deviation (SD). We used the statistical analysis ofthe Excel package .Raspberries are known to be rich in minerals . 12 main elements that form a descending series havebeen identified: K > P > Mg \u2265 Mo > Ca > S \u2265 Ni > Zn >> Mn > Se > Fe \u2265 Co. Among the macronutrients, K has hadthe highest concentration, which is observed in fruits and otherberry crops \u2013 actinidia, blackberries, strawberries, blueberries.The highest value of K from 20.34 to 22.65 wt % was accumulatedin 6 varietal samples \u2013 Poranna Rosa, YubileynayaKulikova, Zhar-Ptiza, Erika, Atlant and Pingvin. The lowestK content of 5.62 wt % was observed in the fruits of the cultivarCarolina (Table 2). In raspberries of early and late ripeningperiods, a 3\u20134 % higher accumulation of K was noted, whichmay be associated with the genotype of the cultivarsDifferences in the accumulation of K in raspberries withvarious fruits colors were revealed. In the berries of darkcoloredand red cultivars of raspberries, the average contentof K was 18.22 and 15.91 wt %, respectively. In light-coloredberries , the content of K ranged from14.71 (Maravilla) to 21.88 (Zhar-Ptiza) and in yellow-coloredberries it was 20.34 (Poranna Rosa) by weight %, respectively.Akimov et al. (2021) also mentioned the high content of K inyellow-colored raspberries of the cultivar Zheltuy Gigant. The content of K in raspberries of domestic and foreign selectioncultivars was on average 18.28 and 16.54 wt %, respectively.However, the identified differences in the accumulation of Kdepending on the color of the berry require further comparativestudies on a larger number of cultivars. The variationcoefficient of K is low (V = 2.121\u20135.707 %), which indicatesa stable intake of this element in raspberries. In the humanbody, K is necessary for the work of the heart muscle, maintainingacid-base and water balance. In ionic form, K increasesthe concentration of other ions and is found in all the organsof the human body .The comparative content of macroelements P, Mg and Cain raspberries is presented in Figure 2.The content of P in raspberries varied from 1.59 wt %(PoklonKazakovu) to 5.19 wt % (Enrosadira). The averagecontent of P in raspberries, depending on the ripening terms,varied within: in berries of early ripening cultivars, its contentwas 4.29; of medium ripening, 3.27 and of late ripening,4.81 wt % respectively; the differences were statistically significantat p \u2264 0.05. In berries of foreign selection cultivars,P content is on average 1.5\u20132.0 % higher than in berries ofdomestic cultivars. P is involved in many physiological processes,including energy metabolism (in the form of ATP),regulation of acid-base balance, is part of phospholipids,nucleotides, nucleic acids, is necessary for bone mineralization.The differences in the content of Mg in raspberries wereless expressed than in the content of P \u2013 from 1.05 wt %(Poklon Kazakovu) to 3.31 wt % (Zhar-Ptiza). The significantdifferences in the content of Mg in berries depending on thecolor of the berries and origin have not been established. Inthe human body, Mg is a coactor of many enzymes, includingenergy metabolism, it is involved in protein synthesis and isnecessary to support homeostasis .Ca ions are involved in blood clotting processes, as wellas in ensuring constant osmotic pressure. It is involved inthe processes of cell growth and development, it is a part ofenzymes and affects metabolism and immunity . According to Jeong et al. (2008), the main elements inthe composition of raspberries are K, P and Ca.The content of S in raspberries ranged from 0.12\u20130.16 wt % to 0.26\u20130.48 wt % .Raspberries contain a group of trace elements \u2013 Mn, Fe, Co,Ni, Zn, Se and Mo. According to the results of our research,Mo in raspberries was contained in the concentrations comparableto Ca and ranged from 1.29 wt % (Poklon Kazakovu andKaramelka) to 4.63 wt % (Yubileynaya Kulikova) . Thehigh content of Mo was distinguished in the cultivars Atlantand Zhar-Ptiza \u2013 4.01 and 4.07 wt %, respectively.The content of trace elements Zn, Fe, Se and Co in raspberriesdid not exceed 0.35 wt %. The highest content ofSe from 0.27 to 0.31 wt % was found in the berries of thecultivars Brice, Zhar-Ptiza, Atlant and Medvezhonok. Theminimum content of this important trace element (0.04 wt %)was noted in the berries of the cultivars Poklon Kazakovu,Enrosadira and Maravilla . The content of Zn in raspberriesranged from 0.06 (Enrosadira) to 0.25 wt % (Heritageand Samorodok).The accumulation profiles of Fe and Co in the ash residueof raspberry fruits coincided. The maximum accumulation ofthese elements was noted in the berries of the cultivar YubileynayaKulikova (0.25 and 0.20 wt %) and Enrosadira andBrice (0.18 and 0.19\u20130.13 wt %). The average content of Fefrom 0.11 to 0.15 wt % was found in the berries of the cultivarsKaramelka, Maravilla, Heritage and Evraziya.The proportion of Se in the raspberries of most cultivarswas from 0.13 to 0.31 wt %. The maximum content of thistrace element was found in raspberries of the cultivars Pingvin,Medvezhonok, Elegantnaya, Atlant, Zhar-Ptiza and Brice. Theminimum content of Se (0.4 wt %) was found in the berriesof the cultivars Enrosadira, Maravilla and Poklon Kazakovu.Among the cultivars with a high density of berries, the cultivarAtlant stood out, in the ash residue of which the content of K,Mn, Fe, Se and Mo was 1.3, 1.5, 3.8, 1.8 and 1.6 times morethan in the berries of other late ripening cultivars. There isevidence that the increase in Se in food in Finland has clearlyincreased due to the use of fertilizers with the addition of Se.K, Mg, Ca, Fe, Zn and Mn have been noted as the mainelements that are found in red raspberries of the cultivar Willamette. There is evidencethat Zn and other elements from the group of heavy metalshave antimicrobial effect . Three key traceminerals, the role of which in antioxidant protection graduallyattracts more and more attention, are Zn, Se and Fe. Overthe past 20 years, a significant amount of evidence has beenaccumulated in favor of the role of these elements as cellularantioxidants . One of the ways in which Znacts as an antioxidant is the induction of metallothioneins,a group of small molecule amino acid residues, the productionof which is induced by Zn in many tissues, includingthe liver, intestines and kidneys. Metallothioneins have beenshown to scavenge free radicals and bind certain oxidants ina relatively inert state and have been shown to act in this wayunder a variety of conditions, including radiation exposure,drug toxicity, ethanol toxicity, and mutagenesis . Se is an essential element of the antioxidant defensesystem of the human body, has an immunomodulatory effect,and participates in the regulation of the action of thyroid hormones.In the raspberry fruits of all samples, a sufficiently high,slightly varying from the genotype, content of Ni was found,which ranged from 0.35\u20130.38 wt % to 0.44\u20130.58 and 0.76 wt % respectively . Ni is a transitional elementwidely distributed in the environment, air, water and soil.Its accumulation can occur from natural sources and anthropogenicactivities. Although Ni is ubiquitous in the environment,its functional role as a trace mineral for animals andhumans has not yet been recognized. The phytoextraction ofNi depends on the level of the concentration of Ni in the soil.According to the total content of elements in the ash offruits, the following cultivars were distinguished: Pingvin, YubileynayaKulikova, Medvezhonok, Elegantnaya, Zhar-Ptiza,Atlant, Brice, Poranna Rosa, Erika, Enrosadira and Heritage,in the ash residue of which 29\u201337 of weight % contained thedetermined elementsThe correlation analysis allows to determine the relationshipbetween mineral elements (Table 3). The highest correlationexists between the elements S\u2013Mg (r = 0.9603), Co\u2013S(r = 0.9603), Se\u2013Mg (r = 0.8587) and Co\u2013Ca (r = 0.8577).The average correlation (r = 0.61\u20130.73) was found betweenS\u2013P, Mn\u2013Ca, Co\u2013Fe, Se\u2013Ca and S, Mo\u2013S, P and Fe. A lowcorrelation (r = 0.41\u20130.55) was noted between Ca\u2013S, Mn\u2013S,Fe\u2013S, Ni\u2013Co, Zn\u2013Mn, Fe\u2013Mg and Mo\u2013Mg. There was practicallyno correlation (r = 0.0085\u20130.0087) between Se\u2013Niand Mo\u2013Ca.In the fruits of repair raspberries, 12 mineral elements havebeen identified, the content of which varies depending on thegenotype.The genetic sources of high total accumulation of macroandmicroelements in the berries are Pingvin, YubileynayaKulikova, Medvezhonok, Elegantnaya, Zhar-Ptiza, Atlant,Brice, Poranna Rosa, Erika, Enrosadira and Heritage.In the selection it is proposed to use the cultivars Medvezhonok,Zhar-Ptiza and Atlant as the sources of increasedcontent of Mg, Mo and Se; the cultivar Yubileynaya Kulikovaas the source of accumulation of Ca, Mo and Fe; the cultivarsHeritage, Samorodok and Atlant as the source of high contentof Zn.The authors declare no conflict of interest.Akimov M.Yu., Koltsov V.A., Zhbanova E.V., Akimov O.M. Nutritionalvalue of promising raspberry varieties. In: IOP ConferenceSeries: Earth and Environmental Science. 2021;640:022078. 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Search and creation of parental forms of primocaneraspberry to improve its assortment. Sadovodstvo i Vinogradarstvo =Horticulture and Viticulture. 2020;1:10-16. DOI 10.31676/0235-2591-2020-1-10-16. (in Russian)Ferlemi A.-V., Makri O.E., Mermigki P.G., Lamari F.N., GeorgakopoulosC.D. Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo andin vitro: investigation of the effect on calpains, antioxidant andmetal chelating properties. Exp. Eye Res. 2016;145:258-268. DOI10.1016/j.exer.2016.01.012.Frassinetti S., Bronzetti G.L., Caltavuturo L., Cini M., Croce C.D. Therole of zinc in life: a review. J. Environ. Pathol. Toxicol. Oncol. 2006;25(3):597-610. DOI 10.1615/jenvironpatholtoxicoloncol.v25.i3.40.Gambardella M., Contreras E., Alcalde J., Neri D. Phenotyping primocanefruiting trait in raspberry (Rubus idaeus). Acta Hortic. 2016;1133:67-74. DOI 10.17660/ActaHortic.2016.1133.11.Genchi G., Carocci A., Lauria G., Sinicropi M.S., Catalano A. Nickel:human health and environmental toxicology. Int. J. Environ. Res.Public Health. 2020;17(3):679. DOI 10.3390/ijerph17030679Gins \u041c., Gins V., M\u043etyleva S., Kulikov I., M\u0435dvedev S., Kononkov P.,Pivovarov V. Mineral composition of amaranth (Amaranthus L.)seeds of vegetable and grain usage by arhivbsp selection. PotravinarstvoSlovak J. Food Sci. 2018;12(1):330-336. DOI 10.5219/863.GOST 26929-94. Raw material and food-stuffs. Preparation of samples.Decomposition of organic matters for analysis of toxic elements.Moscow, 2002. (in Russian)Jennings S.N., Graham J., Ferguson L., Young V. New developments inraspberry breeding in Scotland. Acta Hortic. 2016;1133:23-28. DOI10.17660/ActaHortic.2016.1133.4.Jeong C.-H., Choi S.-G., Heo H.-J. Analysis of nutritional compositionsand antioxidative activities of Korean commercial blueberry andraspberry. J. Korean Soc. Food Sci. Nutr. 2008;37(11):1375-1381.DOI 10.3746/jkfn.2008.37.11.1375.Kazakov I.V., Aitzhanova S.D., Evdokimenko S.N., Sazonov F.F., KulaginaV.L., Andronova N.V. Small Fruit Crops in Central Russia.Moscow, 2016. (in Russian)Kowalenko C.G. Accumulation and distribution of micronutrients inWillamette red raspberry plants. Can. J. Plant Sci. 2005;85(1):179-191. DOI 10.4141/P03-107.Makuev G.A., Omarov Sh.K., Radzhabova G.B. Mineral compositionof berries of perspective grape varieties of foreign selectionin the conditions of southern Dagestan. Me\u017edunarodnyj Nau\u010dno-Issledovatel\u2019skij \u017durnal = International Research Journal. 2018;67(1-2):100-103. DOI 10.23670/IRJ.2018.67.078. (in Russian)Mazzoni L., Perez\u2010Lopez P., Giampieri F., Alvarez\u2010Suarez J.M., GasparriniM., Forbes\u2010Hernandez T.Y., Quiles J.L., Mezzetti B., BattinoM. The genetic aspects of berries: from field to health. J. Sci.Food Agric. 2016;96(2):365-371. DOI 10.1002/jsfa.7216.Meathnis F.G., Ichida A.M., Sanders D., Schroeder J.I. Roles of higherplant K+ channels. Plant Physiol. 1997;114(4):1141-1149. DOI10.1104/pp.114.4.1141.Moreno-Medina B.L., Casierra-Posada F., Cutler J. Phytochemicalcomposition and potential use of Rubus species. Gesunde Pf lanzen.2018;70(2):65-74. DOI 10.1007/s10343-018-0416-1.Motyleva S.M. Guidelines for the analysis of ash elements and mineralinclusions in plant organs by energy dispersive spectrometry on ananalytical SEM. Moscow; Saratov, 2018. (in Russian)Motyleva S.M., Kulikov I.M., Marchenko L.A. EDS analysis for fruitPrunus elemental composition determination. Mater. Sci. Forum.2017;888:314-318. DOI 10.4028/www.scientific.net/MSF.888.314.Nile S.H., Park S.W. Edible berries: bioactive components and their effecton human health. Nutrition. 2014;30(2):134-144. DOI 10.1016/j.nut.2013.04.007.Nilova L.P., Ikramov R.A., Malyutenkova S.M., Veryaskina A.S. Investigationof mineral composition during processing of wild berries.Vestnik Vorone\u017eskogo Gosudarstvennogo Universiteta In\u017eenernyhTehnologij = Proceedings of the Voronezh State University of EngineeringTechnologies. 2018;80(1):151-156. DOI 10.20914/2310-1202-2018-1-151-156. (in Russian)Nordberg G.F., Fowler B.A., Nordberg M., Friberg L.T. (Eds.) Handbookon the Toxicology of Metals. Acad. Press, 2007. DOI 10.1016/B978-0-12-369413-3.X5052-6.Nutrition hygiene: Sound nutrition. In: Physiological standards ofenergy and nutrients for various population groups in the RussianFederation: methodic guidelines MR 2.3.1.0253-21. Approved bythe Russia\u2019s Chief Public Health Officer July 22, 2021. Moscow,2021. (in Russian)Opara E.C., Rockway S.W. Antioxidants and micronutrients. Diseasea-Month. 2006;52(4):151-163. DOI 10.1016/j.disamont.2006.05.002.Orze\u0142 A., Simlat M., Danek J. Directions in raspberry and blackberrybreeding program conducted in NIWA Berry Breeding Ltd.,Brzezna, Poland. Acta Hortic. 2016;1133:9-34. DOI 10.17660/ActaHortic.2016.1133.5.Pereira C.C., Silva E.N., Souza A.O., Vieira M.A., Ribeiro A.S., CadoreS. Evaluation of the bioaccessibility of minerals from blackberries,raspberries, blueberries and strawberries. J. Food Compos.Anal. 2018;68:73-78. DOI 10.1016/j.jfca.2016.12.001.Pochitskaya I.M., Komarova N.V., Kovalenko E.I. Study of antioxidantactivity and mineral composition of berry raw material. Pi\u015deva\u00e2Promy\u0161lennost\u02b9: Nauka i Tehnologii = Food Industry: Science andTechnology. 2017;1:68-75."} +{"text": "The authors wish to make the following changes to their paper .Original:1,*, Ming-Der Wu 1, Chao-Lin Chang 2, Hsun-Shuo Chang 3, Chiou-Fung Chyu 4 and Yueh-Hsiung Kuo 4,5,6,7Ming-Jen Cheng 1Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan; wmd@firdi.org.tw2Product & Process Research Center (PPRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan; ccl@firdi.org.tw3School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; hschang@kmu.edu.tw4Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; cmj@firdi.org.tw (C.-F.C.); yhkuo800@gmail.com (Y.-H.K.)5Department of Biotechnology, Asia University, Taichung 413, Taiwan6Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan7Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan*Correspondence: chengfirdi@gmail.comTo be replaced with:1,\u2020, Ming-Der Wu 1, Chao-Lin Chang 2, Hsun-Shuo Chang 3, Chiou-Fung Chyu 4,\u2020 and Yueh-Hsiung Kuo 5,6,7,*Ming-Jen Cheng 1Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan; chengfirdi@gmail.com (M.-J.C.); wmd@firdi.org.tw (M.-D.W.)2Product & Process Research Center (PPRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan; ccl@firdi.org.tw3School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; hschang@kmu.edu.tw4Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; cmj@firdi.org.tw5Department of Biotechnology, Asia University, Taichung 413, Taiwan6Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan7Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan*Correspondence: kuoyh@mail.cmu.edu.tw\u2020These authors contributed equally to this work.Original:Y.-H.K. and M.-J.C. designed the research; M.-D.W., C.-F.C., H.-S.C. and M.-J.C. performed the research; C.-L.C. and Y.H.K. conducted biological assays, Y.-H.K. and M.-J.C. helped with structure elucidation, M.-J.C. organized the data and wrote the paper. All authors have read and agreed to the published version of the manuscript.To be replaced with:Y.-H.K. is responsible for the main research framework; Y.-H.K. and M.-J.C. designed the research; C.-F.C. performed the chemical and structure elucidation research; C.-L.C., M.-D.W. and H.-S.C. conducted antifungal assays, Y.-H.K. and M.-J.C. helped with structure elucidation, Y.-H.K. and M.-J.C. organized the data and M.-J.C. wrote the paper. All authors have read and agreed to the published version of the manuscript.The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated."} +{"text": "The research described in ref. 44 has been published, and the full details of this reference are included below:In the original article at the time of publication, ref. 44 had only been uploaded to ChemRXiv (DOI: RSC Adv., 2020, 10, 40284\u201340290.44 S. T. Ngo, H. M. Nguyen, L. T. Thuy Huong, P. M. Quan, V. K. Truong, N. T. Tung and V. V. Vu, Assessing potential inhibitors of SARS-CoV-2 main protease from available drugs using free energy perturbation simulations, The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Atriplex was based solely on morphological characters and leaf anatomy. The latest worldwide phylogenetic study of Atriplex significantly improved our knowledge about the relationships within the genus, but a new classification has not been put forward thus far. Here we re-evaluate the taxonomy of C4-species of Atriplex that are native to Russia. Seven species are classified into two sections, A.sect.Obione , and A.sect.Obionopsis (A.fominii and A.tatarica). Although the majority of Eurasian C4-species have similar morphology, leafy inflorescence is a typical character for A.sect.Obione. The members of A.sect.Obionopsis are characterised mostly by aphyllous inflorescences, but some species have leafy inflorescences. Geographically, almost all members of A.sect.Obione are confined to Central Asia, although A.rosea is a typical Mediterranean element and A.argentea occurs in North America. The representatives of A.sect.Obionopsis are distributed mostly in the Mediterranean and the Irano-Turanian floristic region. The alien status of A.rosea, A.sibirica and A.tatarica is discussed. Atriplexflabellum, a desert species from the Irano-Turanian region, is reported for the first time from Russia as a casual alien. This species occupies a phylogenetic position distant from both aforementioned sections. An identification key to all C4-species of the genus growing in Russia is given, and a sectional checklist with updated nomenclature and revised synonymy is provided.For a long time, the systematics of Atriplex L. is the largest genus in the subfamily Chenopodioideae and Kranz (C4) anatomy in the female flowers: A.subgen.Atriplex with marginally connate valves and A.subgen.Pterotheca (Aellen) Sukhor. with ventrally fused valves. The valves imitate bracteoles and pairs of them form bract-like covers enclosing each female flower. The type subgenus comprised several sections, characterised by the degree of valve fusion and their sclerification, leaf anatomy, the type of diurnal leaf movements, as well as their fruit and seed characters.The classification system of rs e.g., ; additio anatomy . In the anatomy , Atriple3-species, especially those of A.sect.Atriplex and A.sect.Teutliopsis Dumort. emend. Sukhor. , as well as a distant position of A.cana C.A.Mey. from other members proposed by 4-species of the genus comprise a monophyletic clade Asch. & Graebn. and A.sect.Obione (Gaertn.) Reichenb., differing mainly by the degree of valve fusion half of their length Sukhor. [= A.schugnanica Iljin], A.pamirica Iljin, A.paradoxa Nikitina, A.pratovii Sukhor., A.pungens Trautv., A.recurva D\u2019Urv., A.rosea L., A.sphaeromorpha Iljin, A.tatarica L., A.tianschanica U.P.Pratov, and A.tornabenei Tineo). Atriplexsect.Obione comprised A.belangeri (Moq.) Boiss., A.centralasiatica Iljin and A.sibirica L. were included in the latest molecular phylogenetic study of the genus, and they fell into two phylogenetic lineages with different positions on the tree within the large C4-group based on the literature data and the examined specimens. The results were generalised and schematically presented over the basemap of first-level administrative subdivisions of Russia. Distribution areas were evaluated for their native core and secondary dispersal based on herbarium specimens and our personal observations in the field, thus separating the territories where the species occur in their natural habitats from those where the species are confined exclusively to ruderal or other man-made habitats.Distribution maps were prepared using SimpleMappr online tool Reichenb. and A.sect.Obionopsis (Lange) Dumort., according to their phylogenetic position that indicate the works previously considered as places of valid publication.The Cposition . The latTaxon classificationPlantaeCaryophyllalesChenopodiaceae\ufeff(Gaertn.) Reichenb., Uebers. Gew.-Reich.: 164 (1828); C.A.Mey. in Ledeb. et al., Fl. Altaic. 4: 315 (1833).42F0D9AF-984D-50A0-86F0-F2D5670A7F05Obione Gaertn., De Fruct. 2: 198 (1791). \u2261 Obionesect.Atriplicina Moq., Chenop. Monogr. Enum.: 70 (1840), nom. inval. (Art. 22.2). \u2261 Atriplexsubgen.Obione (Gaertn.) Hook.f., Student Fl. Brit. Isl.: 320 (1870); Volkens in Engler & Harms, Nat. Pflanzenfam. 3: 66 (1893). \u2261 Atriplexsect.Atriplicina Volkens in Engler & Harms, Nat. Pflanzenfam. 3: 66 (1893), nom. illeg. (Art. 52.1). \u2261 Obionesect.Protobione Aellen, Verh. Naturf. Ges. Basel 49: 133 (1938), nom. inval. (Art. 22.2). Type species: Obionemuricata Gaertn. (\u2261 Atriplexsibirica L.). \u2261 Atriplex [unranked] Sclerocalymma Asch., Fl. Prov. Brandenburg 1(2): 578 (1864), syn. nov. = Atriplexsect.Sclerocalymma (Asch.) Asch. & Graebn., Syn. Mitteleur. Fl. 5(1): 139 (1919). \u2261 Atriplexsect.Roseae Aellen, Bot. Jahrb. Syst. 70(1): 39 (1939), \u201cRosea\u201d, nom. illeg. (Art. 52.1). Type species: Atriplexrosea L. \u2261 Atriplex [unranked] Argenteae Standl. in Britton, N. Amer. Fl. 21: 46 (1916), syn. nov. = Atriplexsubsect.Argenteae (Standl.) S.L.Welsh, Rhodora 102: 420 (2001). Type species (Art. 10.8): Atriplexargentea Nutt. \u2261 Annuals; inflorescences leafy; glomerules loosely arranged.A.altaica, A.centralasiatica, A.pamirica, A.sibirica), in the Aralo-Caspian floristic region (A.sphaeromorpha), in the Mediterranean (A.rosea), and in North America (A.argentea Nutt.). Five species are native to Russia . The Central Asian species are mostly confined to mountain steppes and screes in South Siberia, but A.centralasiatica and A.sibirica can be found also in saline and ruderal habitats. Atriplexrosea and A.sphaeromorpha are typical lowland species with similar morphology but different distribution patterns. The first species, with predominantly Mediterranean distribution, was considered native in the southern part of Eastern Europe Dumort., Bull. Soc. Bot. Fr. 20: xiii (1873).15BE0B63-5EB8-5F59-A4AB-79081470998FAtriplex [unranked] Obionopsis Lange, Haandb. Danske Fl., ed. 2, [7]: 635 (1859).Type species: Atriplexarenaria J.Woods 1849, non Nuttall 1818 (= Atriplexlaciniata L.). \u2261 Atriplexsect.Psammophila Sukhor., Ann. Naturhist. Mus. Wien 108 B: 388 (2006), syn. nov. Type species: Atriplexdimorphostegia Kar. & Kir. = Annuals; inflorescences aphyllous or bracteate, rarely leafy in the lower and middle parts; glomerules loosely or densely arranged.A.dimorphostegia Kar. & Kir., A.fominii Iljin, A.kalafganica Podlech, A.laciniata L., A.lasiantha Boiss., A.olivieri Moq., A.ornata Iljin, A.paradoxa Nikitina, A.pratovii Sukhor., A.pungens Trautv., A.recurva d\u2019Urv., A.schugnanica Iljin, A.tatarica L., and A.tornabenei Tineo.This section includes Atriplexparadoxa is the only species native to Central Asia (Tian-Shan Mountains). Two species are present in Russia: A.fominii (not shown on the map), which is restricted to the western shore of the Caspian Sea in Dagestan and Azerbaijan .Members of this section are distributed mostly in the Irano-Turanian floristic region, with extensions into the Mediterranean and Western Europe. erbaijan , and theica Fig. . In the Obionopsis as a section of Atriplex, but the nomenclatural significance of Du Mortier\u2019s publication was overlooked.Chenopodiaceae) was published in 1859 and consisted of 172 pages, which agrees with the printer\u2019s signatures.The second edition of Lange\u2019s \u2018Haandbog i den Danske Flora\u2019 was published in 7 parts during 1856\u20131859 . These pAtriplexsect.Obione and A.sect.Obionopsis.Considering the latest phylogenetic results, many morphological characters like annual life form, \u00b1 significant fusion of the valves enclosing the female flowers, indurated lower part of the bract-like cover and heteromorphic seeds, which have been traditionally used in sectional delimitation e.g., , should A.centralasiatica , herbaceous and not inflated.The fusion of the valves of the female flowers can vary considerably within a single species as observed, e.g., in asiatica . This spasiatica . In A.seA.sect.Psammophila (now included in A.sect.Obionopsis) as well as the stalked and herbaceous valves should be re-evaluated as rare synapomorphies among the C4-species of the genus.Seeds are usually dimorphic, red and brown in most members of both sections . In lighA.sect.Obione . We conclude that there are no specific morphological traits that can distinguish both sections.Leafy inflorescences, which were considered characteristic of t.Obione , are als4-species of Atriplex growing in Russia, only A.tatarica and can be found in a wide range of habitats including saline soils, same as in more southern regions of temperate Eurasia.From all the Cica Fig. seems toica Fig. . It is fica Fig. , with poica Fig. . In the Russia\u201d , but itsAtriplexsibirica is native to Central Asia and South Siberia (A.rosea) and correctly identified by A.sibirica in Primorsky Kray is reported here: \u201cVladivostok town, Ugol\u2019naya railway station, gravely substrate, 9 Aug 1988, T. Nechaeva s.n.\u201d . Among several sheets collected from this locality by T. Nechaeva, only one specimen belongs to A.sibirica, whereas all other specimens were correctly identified as A.tatarica. In European Russia, A.sibirica was known only from two provinces .F29764A8-B47D-5855-B726-4F818CD797ACObioneflabellum (Bunge) Ulbr. in Engler & Prantl, Nat. Pflanzenfam., ed. 2, 16c: 506 (1934). Type: Iran. \u201cPersia, in montosis salsis ad orientem urbis Meschhed, inter Faz et Tabatkuh prov. Khorassan\u201d, A. Bunge . Image available at https://plant.depo.msu.ru/public/scan.jpg?pcode=MW0058941.In Russia, the species occupies ruderal habitats. Within its native distribution range, it occurs in the desert zone on sandy and loamy soils in lowlands and foothills.Atriplexflabellum is a typical desert plant, and its populations cannot become established in the extreme north of the boreal zone. For this reason, we presume that this population is most likely extinct now.Casual alien. Afghanistan, Iran, Kazakhstan (south and south-east), Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan.Russia (Tyumen Oblast) Fig. .A.flabellum is distant to both A.sect.Obione and A.sect.Obionopsis; this species belongs to the basal grade within a large clade encompassing the majority of the Old World species of the genus (A.subgen.Pterotheca (Aellen) Sukhor. , whose Atriplexflabellum is unexpected. Two more species of the C4-clade of Atriplex, A.dimorphostegia and A.pungens (both belonging to A.sect.Obionopsis), occur in West Kazakhstan at their western distribution limit (more detail in This Russian record of 4-species of Atriplex occurring in Russia, places them into two large groups, which are morphologically similar but geographically rather distinct.A new, phylogeny-based classification of the CThe phylogenetic circumscription of these groups shows that many characters that evolved in these lineages are highly convergent; thus it is impossible to find any clear morphological differences between these lineages. They can be characterised by different tendencies in certain diagnostic characters.Atriplex worldwide. In addition to the gaps in the recent phylogenetic studies, for which some important species have not been sampled yet, a significant difficulty is presented by the vast corpus of old taxonomic literature, which has never been evaluated for the infrageneric nomenclature.This classification is the first step towards a new phylogeny-based revision of the taxonomy of Atriplex species readily colonise disturbed habitats and spread widely to new territories next to or even far away from their native distribution areas. In addition to the first record of A.flabellum, further records of non-native species are expected in Russia, especially those with the ranges located close to the country, e.g. A.dimorphostegia and A.pungens.Many"} +{"text": "Dysphagia is a symptom associated with an array of anatomical and functional changes which must be assessed by a multidisciplinary team to guarantee optimal evaluation and treatment, preventing potential complications.The aim of the present study is to present the combined protocol of clinical and swallowing videoendoscopy carried by ENT doctors and speech therapists in the Dysphagia Group of the ENT Department - University Hospital.Retrospective study concerning the use of a protocol made up of patient interview and clinical examination, followed by an objective evaluation with swallowing videoendoscopy. The exam was performed in 1,332 patients from May 2001 to December 2008. There were 726 (54.50%) males and 606 (45.50%) females, between 22 days and 99 years old.We found: 427 (32.08%) cases of normal swallowing, 273 (20.48%) mild dysphagia, 224 (16.81%) moderate dysphagia, 373 (27.99%) severe dysphagia and 35 (2.64%) inconclusive exams.The combined protocol (Otolaryngology and Speech Therapy), is a good way to approach the dysphagic patient, helping to achieve early and safe deglutition diagnosis as far as disorder severity and treatment are concerned. Dysphagia happens because of disorders in any of the phases of swallowing . Swallowing unbalance may cause severe pulmonary complications, malnutrition and dehydration - all associated with high morbidity and mortality ratesNumerous studies have been carried out aiming at establishing preventive measures in order to mitigate these complications. Thus, it is very important to very carefully assess swallowing, with clinical and complementary exams involving objective tests such as the Videoendoscopic Swallowing Study (VESS) The guided interview for swallowing disorders aims at shedding some light on the etiological and clinical aspects of the disorder, as well as on patient performance during feeding. Thus, the acquisition of this data enables the examiner to raise hypotheses in order to obtain a possible etiological diagnosis, have knowledge about the presence of associated disorders, cognitive aspects integrity, bronchipulmonary disorders and the patient's general clinical status.The clinical exam aims at helping us understand swallowing dynamics, and it is made up of specific assessment procedures of the anatomical structures involved and the functioning of its phasesClinical evaluation should be complemented by objective methods. In our clinic we routinely do the VESS, which enables the detection of possible anatomical and/ or functional changes of the structures involved in swallowing. It also enables the examiner to assess swallowing efficacy and the very integrity of the mechanisms which protect the airway, simulating a meal with food of different consistencies and quantities, keeping a direct view through the fiberoptic deviceStudies have shown that the speech evaluation is sensitive to detect and classify changes to the preparatory, oral and pharyngeal phases. These data, added to the VESS analysis enables the physician to do an objective evaluation of the pharyngeal phase of deglutition and, consequently, a more complete and more accurate diagnosisThe goal of the present paper is to introduce the clinical and VESS assessment protocol created in a joint work between otolaryngologists and speech therapists at the Dysphagia Ward of the ENT Department of our Institution.The present study protocol was approved under record # 412/02 by the Ethics Committee for Research Project Analysis - CAPPesq, of our Institution. All participants in the study protocol were previously instructed by the researcher in charge, in an accessible language, respecting all guidelines established by the aforementioned committee, and they all freely accepted to participate in the study.From May of 2001 through December of 2008 we carried out 1,332 evaluations using the Joint Protocol for Deglutition Assessment.The protocol was made up by the patient's identification, interview, integrated speech and ENT tests and objective evaluation using the VESS.In the initial interview we obtained information about: baseline disorders, main complaints, history and evolution of the clinical manifestations, tests and treatments done, general health condition, specific deglutition-related complaints , feeding conditions , feeding path , vocal characteristics and issues associated with the nutritional status and repetition pneumonias.In both assessments which were carried out (subjective and objective), the procedure used to prepare the consistencies, patient posture and diet used to assess deglutition were all similar. The sole difference between the procedures was the use of a dye (blue edible dye) for the videoendoscopic evaluation.Thick-easy (Fresenius-Kabi) product: thick liquid: 4.5g of the thickener with 100mL of water; Thick: 9.0g of the thickener with 100mL of water. The solid consistency was obtained by giving the patient the \"salt and water\" snack (We used foodstuff dyed with blue dye (edible dye) in the following consistencies: liquid, thick liquid, paste and solid). The liquid consistency was that of filtered water at room temperature. In order to thicken the liquid and make the paste, we used starch-based food thickener, added to filtered water at room temperature, respecting the standardization of the r\" snack and 1B.FIn order to do the assessments, the patient was instructed to remain seated, keeping his head slightly down - simulating the eating position . As for \u2022Liquids ;\u2022Thickened liquid stuff ;\u2022Paste ;\u20223 of solid).Solids and direct assessment (with food given).\u2022General health status ;\u2022Breathing: type and mode\u2022Phono-articulatory organs ;\u2022oral (vomit and cough);\u2022Saliva deglutition .On the first stage, the exam was made by means of objective questions, observation, touch and asking the patient to move in order to check for the following aspects:The clinical evaluation with the diet was done giving the patient food in the quantities and consistencies discussed above. By means of observation and touch, we assessed the following aspects: mouth opening spontaneity, lip closure capacity; chewing efficiency; tongue mobility efficiency in preparing the food cake; deglutition reflex triggering at the onset of the pharyngeal phase; presence and efficiency of the laryngeal elevation; hawking; gagging or cough before, during or after swallowing; presence of food residues in the oral cavity.The otolaryngologist assessed the patient's structural Pharyngo-laryngeal anatomy and the deglutition function using the fiberoptic device - VESS. The test was carried out with the help of a speech therapist.\u2022\u00ae, 10\" color TV Set model 1022FAVU11;SEMP\u2022\u00ae DMR - E55 DVD video recorderPanasonic\u2022\u00ae A43 micro camera coupled to a Machida\u00ae CA - 34VS2 endoscope coupler;Micro camera Toshiba\u2022\u00ae 3,2mm flexible fiberoptic scopeMachida\u2022\u00ae Metal Hilide power sourceWelch AllynAll the exams were recorded in a DVD, which enabled the examiners to review and digitalize the images obtained. We used conventional video-endoscopic equipment made up of:The fiberoptic device was introduced through the patient's broader nasal cavity, without the use of topical anesthesia, so as not to interfere in Pharyngo-laryngeal sensitivity.The VESS exam routine followed the protocol described by LangmoreWe initially assessed the rhinopharynx, a panoramic view of the Pharyngo-laryngeal area and assessment of its sensitivity. We observed: velopharyngeal closure upon phonation and deglutition; saliva and secretion clearance, saliva aspiration signs, glottic closure and vocal fold mobility. Thus, the fiberoptic scope was broadly moved in order to enable a detailed structural assessment, similarly to what is routinely done by otolaryngologists , 4B.FiguAfterwards, we checked for swallowing capacity and limitations concerning the four types of food aforementioned. This phase also involved a broad panoramic view of the pharynx, larynx and subglottic region at the end of the assessment, looking for aspiration before, during or after swallowing. We assessed issues associated with the main events of the oral and pharyngeal phases of deglutition: tongue base mobility; food containment in the oral cavity; nasal food reflux; presence of food residues after deglutition and where it happened; laryngeal penetration; laryngotracheal aspiration of the food cake and the number of deglutitions needed for the complete clearance of the food cake. We also assessed posture and upper airway protection maneuvers tested during the assessment of deglutition for each specific case and its efficacy.For the function assessment of deglutition, the fiberoptic scope was placed upwards in the pharynx, behind the uvula. Considering that at the exact time of deglutition, the larynx moves up and anteriorly, and because of that we tried to avoid touching pharyngolaryngeal structures which could trigger the gag reflex and compromise the deglutition dynamics and 5B.Fwhite-out phase : velopharyngeal closure; saliva stasis in valleculae and pyriform recesses, signs of saliva aspiration, Pharyngolaryngeal sensitivity reduction; glottic closure changes and/or vocal fold movements, pharyngeal and laryngeal signs suggesting lesion caused by gastroesophageal reflux.Deglutition oral phase: changes to base tongue mobility and early food cake escape.Deglutition pharyngeal phase: nasal reflux, post-deglutition residue, laryngeal penetration, laryngotracheal aspiration, cough reflex.Upper airway protection and posture maneuvers test.Number of deglutitions: spontaneous, requested and the total number of deglutitions for the complete clearance of the food cake.Clinical-endoscopic classification of dysphagia\u2022Normal deglutition (level 0): normal oral contention, reflexes present, no salivary stasis, feeding and aspiration, fewer than three attempts to push for food clearance.\u2022Mild dysphagia (level 1): small post-deglutition stasis, less than three attempts to clear the food cake, no nasal regurgitation and laryngeal penetration;\u2022Moderate dysphagia (level 2): moderate salivary stasis, more post-deglutition stasis, more than three attempts to push for food cake clearance; nasal regurgitation; reduction on laryngeal sensitivity with penetration in the laryngeal vestibule; however without laryngotracheal aspiration;\u2022Severe dysphagia (level 3): major salivary stasis; important worsening in post-swallowing residues, bad or absent propulsion, nasal regurgitation, tracheal aspiration.Clinical-endoscopic classification of dysphagiaFrom May 2001 through December of 2008, we did 1,332 evaluations by means of the Joint Protocol for Deglutition Assessment, involving 726 (54.50%) males and 606 (45.50%) females. Their ages varied between 22 days and 99 years, with a mean age of 59.4 years. We found 427 (32.08%) patients with normal deglutitions, 273 (20.48%) with mild dysphagia, 224 (16.81%) with moderate dysphagia, and 373 (27.99%) patients with severe dysphagia. In 35 (2.64%) patients it was not possible and/or conclusive to do the VESS, and the main reasons which made the exam impossible were: not seeing the glottis , hyperreflexia / nausea / vomits, vasovagal reflex, tachi-dyspnea, sleepiness (medication side effect or cognitive state oscillation), refusal to eat, intense crying, unwillingness to collaborate.Dysphagia is a symptom which involves a number of anatomical and functional changes, which should be approached in a multidisciplinary fashion. Many health-care specialists must work together in order to guarantee proper assessment and access to all the factors associated with it, as well as take all the necessary measures which help control the dysfunction, preventing the potential complications such as malnutrition, dehydration and aspiration pneumonia.Talking specifically about oropharyngeal dysphagia, the multidisciplinary team mustMake sure dysphagia is present,Identify possible etiologies for the dysfunction,Rule out structural components ,Make sure the anatomical and functional structures involved in the oropharyngeal deglutitions are intact,Assess the risk of aspiration pneumonia.In this context, it is necessary to discuss the importance of the joint work between otolaryngologists and speech therapists, trying to clarify data concerning anamnesis and physical exam, paying attention to the comorbidities and changes to anatomical structures and cranial nerves involved in the deglutition process. To carry out a specific clinical assessment by means of observing the patient, investigating the functionality of the phono-articulatory organs and following on the feeding time of these patients, when possible, assessing posture, handling of utensils, difficulties concerning consistencies and quantities, as well as identifying deglutition facilitating maneuvers\u00ae - Fiberoptic Endoscopic Examination of Swallowing Safety, described by Langmore et al. (1988)The functional exam of deglutition - FEESShomecare). It has a good diagnostic agreement when compared to other methodologiesIn our clinic, we chose to call it deglutition videoendoscopy (DVE)The main aspects observed during a functional speech therapy evaluation are the triggering of the deglutition reflex; the feeling of stuck food and the \u201cwet\u201d voice/cough/ hawking. These aspects may be respectively correlated with the deglutition reflex (white out phase), presence of pharyngeal residue and penetration/aspiration - main results observed through DVEWe decided to standardize the food given to the patient, so as to be able to have a uniform protocol which could facilitate the evaluation process and enable us to carry out more homogeneous scientific studiesWe numbered the steps used for an anatomical and functional assessment of the nasal cavities, the mouth, velopharyngeal closure, pharynx, larynx, by means of complementary, subjective and objective assessment, providing examiners with good information concerning structural and functional integrity of the oropharynx, as well as the sensitivity and protection reflexes - paramount for a safe deglutitionDuring the functional assessment of deglutition by DVE, it was possible to obtain further details on the pharyngeal phase of deglutition, which corresponds to the intersection phase between the airways and digestive tract, where the intactness of the protective mechanisms of the airways is paramount to prevent aspiration. It was also possible to topographically locate the site of involvement, the deglutition time when the changes were more evident and significant, the consistency which was more difficult to swallow, and facilitating maneuvers which had a positive impact on the deglutition mechanism for each case. The findings resulting from these evaluations established the safety and efficacy of deglutition, enabling its classification.The oral phase of deglutition involves the participation of the tongue muscles, being the most responsible for pushing the food cake towards the pharynx and, consequently, the key for the efficacy of the deglutitions reflex triggering and that of the entire pharyngeal phaseDeglutition's pharyngeal phase involves a complex integration of neuromuscular and sensorial modes. The most relevant indication for VESS is associated to a detailed evaluation of deglutition in this stage, which contains the main mechanisms of airway protection, confirming the occurrence of penetration or silent aspiration in individuals who do not have clinical signs or symptomsTo study deglutition disorders we need a multidisciplinary team, and in this context we stress the joint work of otolaryngologists and speech therapists. The importance of employing the protocol is to have well established parameters to propose a classification concerning the degree of dysphagia, to help the professionals better share ideas, to assess the best treatment option for each case and to objectively assess patient evolution.Joint ENT and Speech evaluation concerning dysphagic patients under a given protocol enables a careful and complementary approach of the dysphagic patient in relation to etiology, approach definition and patient follow up. Clinical evaluation proved to be a good tool to track changes in deglutition, while the VESS enabled a more objective diagnosis, helping the examiner understand the pathophysiology and to treat the dysphagic patient.Attachments IINSTITUTIONENT / SPEECH THERAPY WARDDYSPHAGIA GROUPDEGLUTITION FUNCTIONAL EVALUATION PROTOCOLDEGLUTITION VIDEOENDOSCOPYI) IDENTIFICATIONname:........................................................................................................ ID:............................Age:............................. birth date:..............................................date:............................Address:.................................................................................................. telephone: .......................Occupation:.................................................................. Companion:..................................................DVD........................... Track.........................II) ANAMNESISDiagnostic:Ward of Origin:Complaint:History of past illnesses:Prior treatment and exams :General health :Medication:Treatment by other professionals:Habits Smoking, how long............................................. Alcohol drinking, how long......................................DEGLUTITIONOral Phase Pharyngeal Phase difficulties chewing L / P / S cough dry productive L / P / S food sticks to the mouth ceiling L / P / S gagging L / P / S delay to start deglutitions L / P / S hawking L / P / S food escaping through the lips L / P / S feeling of food stuck L / P / S pain in the oral cavity L / P / S difficulty to swallow L / P / S delay in swallowing L / P / S pain to swallow L / P / S sialorrheaConsistency............................................................... Quantity....................................Posture.............................. Utensils........................ Temperature.................................. changes to the appetite changes to tasting increase in meal time usual time.................................... current................... tiredness to feedOthers burning / heartburn / reflux intubation time....................................................................................... ) weight loss usual weight................. current weight................BMI............... height:...... dry mouth much saliva pneumonia how many ................................................ when......................................FeedingPer Os NGT gastrostomy/jejunostomy Mixed III) SPEECH THERAPIST\u2019S ASSESSMENT1) General Status :2) Oral languageReceptive:Expressive:3) Breathing Tracheostomy4) Phono-articulatory organs4.1. Morphology and MobilityTeeth present absent Total dental prosthesis Partial dental prosthesis Well adapted MaladaptedCurrent status great good regular badOral sensitivity touch adequate changed thermal adequate altered gustative adequate altered4.2. Reflexes Gag/vomit absent presentCough absent present efficient inefficient4.3. VoiceVocal quality - GRBASI TMF scale utterance/a/:______G(grade): R (roughness): B(breathiness): A(asthenia): S(stress): I(instability):Change Grade 1 mild 2 moderate 3 severe 4 extremeOthers normal dyplophonia hypernasal wet pasty hyponasal bitonal shaky strangled whispered roughSPEECHArticulation: precise imprecise recisaSpeech intelligibility: unintelligible intelligible when focused partially intelligible intelligibleDiadochokinesia rate: PA TA KA PA TA KA RECORDING (date):..............5) Swallowing Assessment5.1. Salivaautomatic voluntary absent normal build up sialorrhea xerostomia laryngeal lift: present absent reduced gagging/cough: Y N wet voice: Y N 5.2. FoodBody and neck posture:........................................................................................Cuff: inflated partially inflated empty Legend: Utensils: CN-straw; CP-cup; CL-spoon; S-syringeObservations: (nausea/vomit and others):.....................................................................................................Chewing:.........................Maneuvers utilized: postural:...............Airway protection:.....................CONCLUSION: Normal deglutition Oral dysphagia Oropharyngeal D Pharyngeal D By consistency: Mild dysphagia ___ Moderate dysphagia ___ Severe dysphagia ____General classification: Mild dysphagia Moderate dysphagia Severe dysphagiadysarthria apraxia aphasia dysphonia dysarthrophonia other:.....................................APPROACH:..............................................Examiner:.......................................................IV) ENT EVALUATION1. Nasal CavitiesSeptum centered deviated R deviated L non-obstructive irregularitiesMucosa normal pale red edematous wet atrophicTurbinates normal hypertrophic2. Rhinopharynx:Mucosa normal pale red edematous wet atrophicTube ostia free obstructed3. Velopharyngeal sphincter:Phonation complete closure local incomplete closure:............... coronal sagittal circular circular with Passavant ring insufficient incompetentDeglutition complete closure local incomplete closure:............... coronal sagittal circular circular with Passavant ring insufficient incompetent4. Hypopharynx Tongue base - mobility adequate altered.............................Valleculae normal lesion saliva stasisEpiglottis normal omega lesion.................................Arytenoids normal hyperemia edema grade.................Interarytenoid region normal hyperemia edema grade.................Pyriform sinuses free obstructed salivary stasis R LPharyngeal sensitivity normal reduced absent increasedMucosa normal edematous rough pachydermia5. Larynx vocal folds mobile others................................ paresis R L paralysis R L arching R L atrophy R L lesion................................. R LVentricular folds normal hyperconstriction R LLaryngeal asymmetry yes noLaryngeal sensitivity upon a mechanical stimulus:Epiglottis normal changedAryepiglottic fold normal changedarytenoids normal changedvocal folds normal changedventricular bands normal changedsaliva aspiration present absentsubglottis normal changed6. Glottic closure complete incomplete consistent inconsistent anterior spindle-like cleft total spindle-like cleft hourglass-shaped cleft7. VESS TableCONCLUSION: Normal deglutition Oral dysphagia oropharyngeal dysphagia Pharyngeal dysphagia By consistency: Mild dysphagia ______ Moderate dysphagia _______ Severe dysphagia _______General classification: Normal deglutition Mild dysphagia Moderate dysphagia Severe dysphagiaAPPROACH: Speech therapy education reassessment High other:____________________Examiner: ________________________________"} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-022-09968-2, published online 08 April 2022Correction to: The original version of this Article contained errors.In the legends of Figures\u00a01, 2 and 3,d, yellow), and the ROI was copied from the ADC map to the TBF map of the software .\u201d\u201cThe region of interest (ROI) was manually drawn on the apparent diffusion coefficient (ADC) map of the software , and the ROI was copied from the ADC map to the TBF map of the software .\u201d\u201cThe region of interest (ROI) was manually drawn on the apparent diffusion coefficient (ADC) map of the software (Additionally, the Author contributions statement,\u201cStudy concept and design: T.T., M.U., and M.M. Acquisition of data: K.I. and M.O., development of the software for image analysis: R.N. Analysis and interpretation of data: F.T. and M.M. Drafting of the manuscript: F.T. and M.M. Statistical analysis: F.T. Study supervision: M.M. and H.S. All authors reviewed the manuscript.\u201dnow reads:\u201cStudy concept and design: F.T., M.U., and M.M. Acquisition of data: K.I. and M.O., development of the software for image analysis: R.N. Analysis and interpretation of data: F.T. and M.M. Drafting of the manuscript: F.T. and M.M. Statistical analysis: F.T. Study supervision: M.M. and H.S. All authors reviewed the manuscript.\u201dThe original Article has been corrected."} +{"text": "All authors have read and agreed to the published version of the manuscript.After updating:Conceptualization, S.M.H.; validation, E.B., M.G. and S.M.H.; formal analysis, S.M.H. and P.Z.; data curation and visualization, M.G. and C.P.; writing\u2014review and editing, S.M.H., E.B.; C.P. and P.Z.; project administration, S.M.H. and M.R.N. All authors have read and agreed to the published version of the manuscript.The authors apologize for any inconvenience caused and state that the change does not affect the results of the study and the conclusions drawn from it. The original publication has also been updated."} +{"text": "Oryza AA-genome complex comprises five wild species, O. rufipogon, O. barthii, O. longistaminata, O. glumaepatula, and O. meridionalis. Evolutionary relationships among these five wild species have remained contentious and inconclusive. We found that intron 20 of PolA1, a single-copy nuclear gene, was short (S-type: 141\u2013142 bp) in O. rufipogon, O. barthii, and O. glumaepatula, while long (L-type: ca. 1.5 kb) introns were apparent in O. longistaminata and O. meridionalis. Because Oryza species containing BB, CC, EE, FF, and GG genome showed L-type introns, the S-type intron was probably derived from the L-type intron by the deletion of a 1.4 kb fragment through intramolecular homologous recombination between two tandem TTTTGC repeats. Excluding the large deletion sequence, intron 20 sequence of O. barthii was identical to that of O. longistaminata. As more than 3,470 accessions of O. rufipogon and O. sativa also contained the same intron 20 sequence with O. longistaminata except for single T-nucleotide deletion, which was shared with O. glumaepatuala, the deletion of the T-nucleotide probably occurred in the L-type intron 20 of O. logistaminata. Deletions of a large 1.4 kb fragment and single T-nucleotide within the intron 20 of PolA1 gene were considered as useful DNA markers to study the evolutionary relationships among Oryza AA-genome species. Oryza (2n = 24 to 48) comprises 24 wild species representing 11 genomes: AA, BB, CC, BBCC, CCDD, EE, FF, GG, HHJJ, HHKK and KKLL. It has two cultivated species, O. sativa L. and O. glaberrrima Steud, while the other five species: O. rufipogon (including O. nivara), O. barthii, O. longistaminata, O. glumaepatula and O. meridionalis are regarded as wild species in the AA-genome in Oryza sativa complex in Oryza AA-genome species.142 bp) or L-type . Of the 30 accessions, listed in Oryza diploid species containing AA, BB, CC, EE, FF, and GG genome were analyzed for the intron 20 sequence of PolA1 gene. Within AA-genome species, the length of intron 20 was analyzed by PCR in 35 accessions of O. rufipogon, 18 O. barthii, 21 accessions of O. longistaminata,accessions of 17 accessions of O. glumaepatula, and 16 accessions of O. meridionalis of seedlings were frozen in 2-ml plastic tubes with liquid nitrogen and crushed into fine powder using a multi-beads shocker . Total genomic DNA was extracted by CTAB method . Subsequently, PCR amplification was performed with ExTaq DNA polymerase according to manufacturer\u2019s instruction. The PCR conditions were 40 cycles of 94\u00b0C for 1 min, 58\u00b0C for 1 min for annealing, and 72\u00b0C for 2 min for elongation in a PTC200 thermocycler .As shown in PolA1 genes in Oryza species were registered in the DDBJ as accession nos. (LC638415\u2013LC638446).The amplified PCR products were subjected to 1.0\u20131.5% agarose gel electrophoresis and purified using a PCR purification kit . DNA sequences of the purified PCR products were determined by direct sequencing with the same primer as used for PCR amplification in an automated DNA sequencer ABI310 with a Big Dye Terminator Cycle Sequencing kit . Sequences of the L-type intron 20 were determined by using primers c, d1, and d2 as a sequencing primer . The detPolA1 gene using NCBI web-based Blast sever from the International Rice Research Institute (IRRI) and 446 accessions of O. rufipogon (http://viewer.shigen.info/oryzagenome21detail/index.xhtml) from the National Institute of Genetics (NIG) to confirm sharing of the same one base T-nucleotide deletion in the S-type intron 20 sequences.Sequences of PCR products read by direct sequencing were analyzed to determine the positions for donor and acceptor sites of the intron 20 in the PolA1, are thought to be good markers for determining evolutionary relationships. Previous study by PolA1 gene were differentiated in length among AA, EE, FF and GG genome species in the genus Oryza while the amplicon sizes were identical between AA, BB, and CC genome species.Over the past half century, the utility and potential of various molecular approaches have been effectively used to solve the controversies of evolution and biosystematics that had remained unresolved despite many efforts made through conventional approaches . AlthougPolA1 gene were differentiated into two types, long type (L-type) and short type (S-type), in Oryza species. As shown in ca. 1.1\u20132.6 kb) was observed in BB genome species , CC , EE , FF , and GG (O. sativa Ac221 showed S-type (141 bp) while O. longistaminata W0708 contained both S- and L-type. This result suggested that L-type introns were ancestral to S-type introns and large deletion within the intron 20 happened after the AA-genome species originated.In this study, using a pair of primers a and b , amplifi, W0004) . Two AA-O. rufipogon showed the S-type intron 20 except two accessions W1235 and W1239 . In case of O. longistaminata, 15 accessions showed L type and one accession W1573 contained S-type. Five accessions had both S- and L-type introns. This result indicated that O. longistaminata and O. meridionalis predominantly had the L-type whereas O. rufipogon, O. barthii, and O. glumaepatula contained the S-type. Five accessions of O. longstaminata having both L-type and S-type were probably hybrids between O. longistaminata and O. barthii, which shared the same habitat in West Africa.Within AA-genome species, using a different pair of primers e and f , all accnd W1239 , As SotoOryza species was constructed and O. officinalis, O. eichingeri, O. rhizomatis (CC-genome species) formed a single clade, which was closely related to that of AA-genome species. Oryza australiensis (EE), O. brachyantha (FF), and O. granulata (GG) formed paraphyletic groups those were distantly related to AA-genome species.Although L-type intron 20 sequences of several accessions could not be determined because of sequence heterogeneity , Neighbostructed . Two AA-O. longistaminata as the basal AA-genome species. The ancestor of the Asian Oryza AA-genome species was diverged from ancestor of O. longistaminata in Africa involving the changes from perennial to annual and sympatric speciation during the course of evolution was probably deleted between two tandem TTTTGC repeats in the L-type intron, which resulted in the S-type intron (141\u2013142 bp) and perennial W1956 accessions of O. rufipogon as well as template japonica \u2018Nipponbare\u2019, japonica Ac221, and indica Ac130 of O. sativa containedtropical the same intron 20 sequence with O. longistaminataW1232 except for single T-nucleotide deletion . Interes with two accessions of O. glumaepatula.We found that a large DNA fragment (\u2013142 bp) . Also, tis W0002 . Excludiis W0002 . In detaO. rufipogon, O. barthii, O. longistaminata, O. glumaepatula and O. meridionalis have long been a subject of controversy (O. sativa (IRRI 3K SNP project) and 446 accessions of O. rufipogon , O. rufipogon and O. sativa shared the same one base T-deletion in the S-type intron 20 sequences (O. sativa) and columns FJ and FL in O. rufipogon). While O. longistaminata and O. barthii shared the non T-deletion in their intron 20.The evolutionary relationships among troversy . Based oequences , becauseOryza AA-genome species. Scenario 1: a large deletion of 1.4 kb fragment in the intron 20 first happened in an accession of O. longistaminata when O. barthiioriginated. Then, single T-nucleotide deletion occurred in the intron 20 when common ancestral species of O. rufipogon and O. glumaepatula originated species O. longistaminata and O. meridionalis and three S-type (141\u2013142 bp) species O. rufipogon, O. barthii, and O. glumaepatula. Therefore, three S-type species were derived from ancestral O. longistaminata in South Asia (O. rufipogon), West Africa (O. barthii) and South America (O. glumaepatula). The annual species O. meridionalis was also originated from perennial species O. longistaminata in Australia. Although the mechanism underlying the speciation of these new species from O. longistaminata remains to be resolved, ancestral O. longistaminata accessions except Africa were displaced over time by newly arisen species. These findings could potentially suggest that O. longistaminata was used to distribute in the past not only in Africa but also in Asia and Australia.In this study, we found that intron 20 sequences of the IN and YS planned this study. HAH, SM, HT and PS performed molecular and phylogenetic analyses. HAH and IN wrote manuscript.Supplemental Table 1, 2Supplemental Table 3Supplemental Table 4"} +{"text": "Bacteria play a key role in biogeochemical cycles in natural and anthropogenic ecosystems. In river ecosystems, bacteria intensively colonize silt sediments. Microorganisms are essential for energy conversion, biogeochemical nutrient cycling, pollutant degradation, and biotransformation of organic matter; therefore, bottom sediments can be a source of metabolically diverse microorganisms, including those with promise for industrial biotechnologies. The aim of this work was to isolate and study pure cultures of microorganisms \u2013 producers of industrially important enzymes and decomposers of organic matter \u2013 from bottom sediments of the Ob River. Pork fat and diesel fuel were used as substrates to obtain enrichment and pure cultures for selective cultivation of bacteria with lipolytic and hydrocarbon-oxidizing activity. A total of 21 pure cultures were isolated. The phylogenetic position of the obtained bacterial isolates was determined based on the analysis of 16S rRNA gene sequences. The strains isolated on selective media belonged to representatives of the genera Pseudomonas and Aeromonas (Gammaproteobacteria), and the genus Microvirgula (Betaproteobacteria). The ability of strains to grow on culture media containing pork fat, olive oil and diesel fuel was analyzed. The lipolytic activity of the isolates was evidenced by cultivation on a diagnostic medium containing 1 % tributyrin. The phylogenetic and metabolic diversity of the cultivated non-pathogenic bacterial strains with lipolytic and oil-oxidizing activity revealed in the study indicates the biotechnological potential of the isolates. The most promising strains were M. aerodenitrificans sp. LM1 and P. lini sp. KGS5K3, which not only exhibited lipolytic activity on the diagnostic medium with tributyrin in a wide temperature range, but also utilized diesel fuel, pork fat and olive oil. Bacteria play a significant role in the biogeochemical cyclesin natural and anthropogenic ecosystems. In river ecosystems,bacteria intensively colonize silt sediments . The river microbial network is a directional linearbranched structure shaped by the river flow. Microorganismsare transferred from the water column to the underlyingsediments and enrich them .The branched structure of the river ecosystem contributes toaccumulation of bacteria from surrounding lands, includingurban and industrial areas, wastewater treatment plants andagricultural lands, which also contain soluble components. These include organic matter, nutrientsor toxic compounds, and metals, which affect the activity andabundance of heterotrophic bacteria in bottom sediments.Microorganisms are crucial for energy conversion, biogeochemicalnutrient cycling, pollutant degradation, andbiotransformation of organic matter; therefore, bacteria can beused as bioindicators of aquatic ecosystems . For example, the abundance of Nitrospirae,Betaproteobacteriales, Chloroflexi, and Sphingobacterialesrepresantatives was found to increase in proportion to anincrease in the concentration of nitrogen, which shows highconcentrations due to anthropogenic load. An increasedproportion of Nitrospirae, Sphingobacteriales (Bacteroidetes)and Spirochaetes and a generally decreased abundance ofActinobacteria were observed in sediment communities ofriver ecosystems located near wastewater treatment plants,which indicates the impact of wastewater .Thus, characterization of the composition of bacterialcommunities in the water column and river sediments, as wellas the response of microbial communities to environmentalchanges, can yield valuable information to explore microbialinterrelations and assess the environmental risk . In addition, bottom sedimentscan be a source of metabolically diverse microorganisms,including those promising for industrial biotechnologies.Works that address the species composition and functionsof microbial communities in river ecosystems are few innumber as compared, for example, with those related toecosystems of salt lakes or seas. Microbiological studies ofrivers flowing through the territory of Russia cover mainlytheir sanitary and epidemiological status . A.I. Kopylov and D.B. Kosolapov investigated distributionof bacterioplankton in the lower reaches of the Ob River andprovided measurements of the specific growth rate, and theabundance and distribution of biomass in different parts ofthe river . Other works relatedto microbiological monitoring of the Ob River studied theabundance and distribution of some metabolic groups of microorganisms, including those resistantto antibiotics and phenol . Yetthe species diversity and physiological characteristics of thenative microflora have been poorly studied.The Ob River flows through the territory of Western Siberiaand ranks among the first in terms of length, water content andcatchment area among Eurasian rivers. In the Siberian region,the Ob River is exposed to the greatest anthropogenic load,including demographic, agricultural and industrial impact; itswater quality indicators for the content of certain metals andoil products are considered critical .Therefore, the study of microbial communities in the watercolumn and bottom sediments is of relevance, including thesearch for biotechnologically promising microorganisms \u2013decomposers of organic matterThe aim of this study was to isolate pure cultures ofmicroorganisms-decomposers from bottom sediments ofthe Ob River, analyze their ability to utilize various organicsubstrates, and detect their lipolytic and hydrocarbonoxidizingactivity in different cultivation conditions.Bottom sediment samples were collected in July 2020 in themiddle reaches of the Ob River near the following settlements:Molchanovo , Kolpashevo, Kargasok . Sediments (sandy deposits) sampled froma depth of 1.5 m were put into sterile plastic test tubes andstored at +4 \u00b0C. The pH level of the water at the samplingsites was shifted to slightly alkaline pH values (from 7.5 to8.6) .Strains \u2013 decomposers of organic matter and producersof biotechnologically significant enzymes \u2013 were isolatedby selective cultivation on culture media for lipolytic andhydrocarbon-oxidizing microorganisms. Initial enrichmentcultures from each sampling site were obtained on a selectivemineral medium containing pork fat (1 % of the mediumvolume) used as the only carbon source and on the medium used for hydrocarbon-oxidizing bacteria supplemented with 1 % diesel fuel, as describedin . Samples taken in an amount of0.5 ml from each site were inoculated in 50 ml of the liquidmedium (pH 7.5) containing pork fat in 120 ml glass vialsand cultivated at +28 \u00b0C in oxygen. The first inoculation toobtain hydrocarbon-oxidizing microorganisms was performedby limiting dilutions in 7 ml of the liquid medium in 15 mlglass penicillin vials. After that, the resulting enrichmentcultures were inoculated on agar media of similar compositionto obtain individual colonies. The colonies grown on plateswith enrichment cultures were transferred to GRM broth . Then, the obtained aerobicstrains were cultivated on Petri dishes with GRM broth at+28 \u00b0C.The morphology of enrichment and pure cultures wasanalyzed by phase contrast microscopy using \u00d7100 immersion lens.The ability of strains to oxidize petroleum products wasestimated using a liquid culture medium supplemented with 1 % diesel fuel as anorganic substrate. The inoculations were performed in 15 mlpenicillin vials filled with the medium to 1/3 (5 ml). Incubationproceeded at +28 \u00b0C. The growth was assessed by mediumturbidity and using microscopy. To confirm the hydrocarbonoxidizingactivity of individual strains, inoculations of thedense mineral medium without yeast extract were performed on Petri dishes with the additionof 0.1 ml of diesel fuel spread together with the inoculum onthe medium surface.The ability to utilize animal and vegetable fat was studiedusing a mineral culture medium containing 1 % pork fat or 1 % olive oil. The cultivationprocedure was as follows: 0.25 ml of molten sterile pork fator olive oil was spread on Petri dishes filled with 25 ml of theagar mineral medium; the inoculum was placed in a dropletof pork fat and spread on the surface of the medium usinga spatula or a bacterial loop.Lipolytic activity was detected using a diagnostic medium(tributyrin agar) containing 0.5 % (w/v) peptone, 0.3 %(w/v) yeast extract and 1.5 % bacteriological agar (pH 7.0)supplemented with 1 % tributyrin .Tributyrin is an ester composed of butyric acid and glycerol.Tributyrin agar is mainly used to detect lipolytic activity inbacteria . Cultures were incubatedat +28, +25, and +4 \u00b0C. After 24 or 48 h of incubation,hydrolysis zones could be observed aroundthe colonies.The phylogenetic position of the obtained strains wasdetermined by sequencing and analyzing 16S rRNA genesequences. Genomic DNA was isolated from cultures using theBiolabmix kit (DU-50) in accordance with the manufacturer\u2019srecommendations (http://biolabmix.ru/). For amplification ofbacterial 16S rRNA genes, which are universal phylogeneticmarkers, primers 27F and 1492R were used. A 50 \u03bcl PCR mixture contained 1x PCRbuffer (Biolabmix), 2.5 mM MgCl2 (Biolabmix), 0.2 mMdNTP mixture (Biolabmix), 10 pM of each primer (Sintol),0.7 U thermostable HS-Taq polymerase (Biolabmix), 3 \u03bclof template DNA (at a concentration exceeding 50 ng); themixture was brought to the final volume with sterile deionizedwater.The 16S rRNA genes were amplified in accordance withthe procedure described in .Sequencing of the obtained DNA sequences was performedusing a genetic analyzer NANOFOR-05 in Scientific andProduction Company \u201cSintol\u201d, Moscow. To obtain a nearlycomplete 16S rRNA gene sequence, the forward primer 27F, the reverse primer 1492R , and the BacV3F primer wereused.The obtained nucleotide sequences of the 16S rRNA geneswere analyzed using the BIOEDIT sequence editor (http://www.jwbrown.mbio.ncsu.edu), the BLAST program in theNCBI GenBank database (http://www.ncbi.nlm.nih.gov), andthe SILVA database classifier . Chimeric sequences were detected using the DECIPHERpackage (http://www2.decipher.codes/FindChimeras.html).The obtained nucleotide sequences of the 16S rRNA genefragments were deposited in the GenBank database under thenumbers: OM212652, OM212653, OM212656\u2013OM212659,OM212664\u2013OM212671.Enrichment and isolation of pure culturesFor isolation of bacterial strains \u2013 producers and decomposersof organic matter \u2013 samples of bottom sediments from themiddle reaches of the Ob River and selective culture mediafor lipophilic and hydrocarbon-oxidizing microorganismswere used. Morphologically homogeneous pure cultureswere isolated from enrichment cultures, which showed highabundance and morphological diversity of cell forms . Strains that exhibited stable growth on GRM agarwere used for further studies. In total, 9 pure cultures wereobtained from separate colonies isolated on the medium usedfor hydrocarbon-oxidizing bacteria, and 12 pure cultures wereisolated on the medium used for lipolytics.Phylogenetic analysisAnalysis of the 16S rRNA gene fragments showed that thestrains belong to Proteobacteria (Gammaproteobacteria andBetaproteobacteria) (see the Table). Proteobacteria oftendominate in the bacterial communities in water and bottomsediments, and their proportion in sediments is typically higherthan that in water .Most of the analyzed strains were representatives ofPseudomonas and Aeromonas (Gammaproteobacteria). Allthe obtained and analyzed fragments of the 677\u20131445 bp DNAsequences showed a high percentage of similarity (99.48\u2013100 %) with sequences of typical strains of microorganismsdeposited in the GenBank NCBI database.A part of the strains was related to opportunistic pathogensbelonging to hazard group II according to the WHO classification(https://bacdive.dsmz.de/). The detected pathogensincluded all Aeromonas strains related to A. veronii (LKar2and LKar3), A. hydrophila (LM7 and KLP3), as well as E. coli(LKol1) and P. putida (LM3 and LM4). Most of the pathogenicstrains were isolated from lipophilic enrichment cultures. Conditionally pathogenic microorganisms grown onthe mineral medium containing pork fat were isolated in ourprevious studies when isolating pure cultures of lipophilicmicroorganisms from wastewater treatment plant effluentand food industry wastewater .Bacterial lipases involved in such metabolic processes ashydrolysis and lipid modification can be virulence factorsfor some phylogenetic groups, which explains numerouspathogens found among lipophilic bacteria .Other bacteria were related to microorganisms that are nonhumanpathogens. Most of the strains were representatives ofthe genus Pseudomonas. The genus Pseudomonas includesa large group of Gram-negative bacteria that exhibit a greatmetabolic diversity, which allows them to utilize a widerange of organic compounds and play important ecologicalroles in the carbon cycling. Pseudomonas are ubiquitous ina wide variety of ecosystems and include many pathogenichuman, animal, and plant species , as wellas mutualistic species, which include the most remarkablerepresentatives of biocontrol strains that protect plants frompathogens .Pseudomonades can degrade various lipids and lipidcontainingcompounds , as well as oilhydrocarbons . Representatives ofthe genus Pseudomonas are often found in river ecosystems,which is evidenced by molecular studies and cultural methods , including isolation of new pseudomonades fromoil-contaminated bottom sediments in China ,dioxin-contaminated bottom sediments in Texas , bottom sediments in India , etc.Analysis of the 16S rRNA gene sequencing performedfor the Mol4a strain showed 100 percentage of similaritywith sequences of P. veronii strains from various habitats, and 99.82 percentage ofsimilarity with the P. veronii type strain isolated from mineralwaters . The KGS3Ps2 strain was foundto be closely related to P. protegens (LS999205) isolated fromsoil, which together with representatives of P. veronii belongsto the Pseudomonas fluorescens group. P. baetica belongs tothe same taxonomic group, and its 16S rRNA gene showed100 percentage of sequence similarity with the KGS3Ps1strain. The type strain of the above bacterium is a pathogenfor sole .The KGS5k1 strain showed the highest percentage ofsimilarity (99.86 %) with an undescribed strain isolated fromsoil and referred to as P. brassicacearum (KT695825), and99.5 percentage of similarity with a valid strain P. chlororaphis(CP027720) isolated from fluviatile loam and related to thePseudomonas chlororaphis taxonomic group. Comparisonof the nearly complete 16S rRNA gene sequence showeda similar percentage of similarity between the Mol4k12 strainand the type strains of different species, namely, P. fildesensis(MK859934) and P. extremaustralis (KX186942), which areclosely related to representatives of P. fluorescens. KGS5k2,KGS5k3, and KGS5k8 strains showed 100 % homology withthe 16S rRNA gene of P. lini (NR_029042) isolated fromrhizosphere soil .The genus Pseudomonas is one of the taxonomically mostcomplex genera . Although the 16S rRNA gene is a universal phylogenetic marker in the bacterial classificationsystem, the analysis of this gene alone does not allowdifferentiation of closely related bacterial species. Recentstudies have shown that multilocus sequence analysis (MLSA)performed for four housekeeping genes enables species identification and facilitatesstrain identification in Pseudomonas . Thus,a more precise determination of the phylogenetic positionof the isolated Pseudomonas strains requires analysis ofadditional molecular markers .Analysis of 16S rRNA gene sequences showed thatLM1, LM2, LM6, LM8, LKol2, and LKol3 strains areidentical and can be assigned to the genus Microvirgula,the class Betaproteobacteria. Interestingly, we earlierisolated the identical 768 bp sequence (GenBank accessionnumber MT476921) that belong to bacteria of the genusMicrovirgula from food industry waste . Representatives of the genus Microvirgula growwell in aerobic and anaerobic conditions, have an atypicalrespiratory type of metabolism, and use oxygen and nitrogenoxides as the final electron acceptors .The genus Microvirgula was first described by Patureau et al.(1998) and was characterized as a new denitrifying bacteriumM. aerodenitrificans isolated from activated sludge. At present,the genus Microvirgula includes two species. The otherrepresentative of M. curvata was isolated from hydrocarboncontaminatedsoil and included onestrain. Comparison of the sequenced fragments of the 16SrRNA genes of LM1, LM2, LM6, LM8, LKol2, and LKol3strains showed that their sequences are identical and exhibit100 % homology with the strain of M. aerodenitrificans(MT367755) isolated from the intestines of wild animals.They also showed 99.79 and 99.86 percentage of similaritywith M. aerodenitrificans Sgly2 isolated from activated sludge and the type strain, M. aerodenitrificansNBRC 15328 (AB680837) isolated from fresh water , respectively.Lipolytic activity of numerous representatives of Pseudomonaswas thoroughly investigated on various substrates,lipolytic enzyme genes were studied and cloned , and their hydrocarbon-oxidizing activity was confirmed. At the same time, only lipolyticactivity on diagnostic media was shown for representativesof the genus Microvirgula, and their lipolytic properties werenot studied in detail. Yet the analysis of Microvirgula genomesavailable in the NCBI database revealed lipolytic enzymegenes. At present, data have been published on the genomesof two strains of M. aerodenitrificans (JHVK01000000 andCP028519) isolated from different bioreactors and one strainof Microvirgula (NZ_QLTJ01000000) with an unidentifiedphylogenetic position, which is a bacterial endophyte of rice.The search for lipolytic enzyme genes in the listed genomesrevealed the presence of lipases and esterases. Additionally,data on sequences of Microvirgula strains isolated frompetroleum-contaminated habitats indirectly indicatetheir hydrocarbon-oxidizing activity.Detection of lipolytic activityof strains using a diagnostic mediumNon-pathogenic strains of different phylogenetic affiliationwith nearly complete 16S rRNA sequences (see the Table)and different growth or morphology characteristics were usedto study lipolytic activity. All the strains grew and formedhydrolysis zones on tributyrin agar after 24\u201348 h of cultiva-tionat +28 \u00b0C, except for P. veronii sp. Mol4, which did notform hydrolysis zones, most likely due to the absence of lipolyticactivity and the use of peptone, the component of theculture medium, as a growth substrate. In contrast to otherstrains with hydrolysis zones of about 3 mm, P. protegenssp. KGS3Ps2, P. brassicacearum sp. KGS5k1, and M. aerodenitrificanssp. LM1 showed a more pronounced lipolytic activityin the form of complete hydrolysis reaction. Additionally,P. protegens sp. KGS3Ps2 and P. brassicacearum sp. KGS5k1exhibited growth and lipolytic activity at +4 \u00b0C.Study of the ability of strains to utilizeorganic substratesIn contrast to Microvirgula strains, Pseudomonas strainsgrown on GRM agar exhibited psychrotolerant propertiesand stable growth at +4 \u00b0C. None of the studied thermotolerantstrains showed stable growth at +50 \u00b0C. There were nosignificant difference in biomass gain on GRM and tributyrinagar at +25 and +28 \u00b0C.On dense media containing 1 % pork fat and 1 % olive oil,strains of M. aerodenitrificans sp. LM1 and P. lini sp. KGS5k3were observed to grow at +25 and +28 \u00b0\u0421. The inoculations onmedia containing pork fat and olive oil at +4 \u00b0C showed thatanimal fat and vegetable oil do not degrade or this process isconstrained at low temperatures. P. protegens sp. KGS3Ps2and P. brassicacearum sp. KGS5k1 did not grow on thesemedia even at +28 \u00b0C despite their more pronounced lipolyticactivity on diagnostic mediaScreening of strains on the selective medium containing 1 %diesel fuel showed that 5 out of 10 strains, namely, P. protegenssp. KGS3Ps2, M. aerodenitrificans sp. LM1, P. fildesensis/extremaustralis sp. Mol4K12, and P. lini spp. KGS5k3 andKGS5k8, are able to grow on a hydrocarbon-containingmedium. To confirm the hydrocarbon-oxidizing activity ofM. aerodenitrificans sp. LM1 and P. lini sp. KGS5k3 \u2013 themost promising decomposers \u2013 additional inoculations werecarried out on a dense mineral medium containing diesel fuelas the only carbon source. The growth of strains was observedafter less than 2 days. It should be noted that P. lini sp. KGS5k3yielded more biomass.The phylogenetic and metabolic diversity of cultivated nonpathogenicbacterial strains with lipolytic and hydrocarbonoxidizingactivity revealed in the study indicates biotechnologicalpotential of the isolates. The most promising strainsare M. aerodenitrificans sp. LM1 and P. lini sp. KGS5k3,which exhibited lipolytic activity on a diagnostic medium ina wide temperature range and utilized such complex organicsubstrates as diesel fuel, pork fat and olive oil. For the firsttime, the ability to oxidize petroleum products and grow onspecific fat-containing substrates was shown for representativesof M. aerodenitrificans. Earlier, only lipolytic activityon diagnostic media was reported for M. aerodenitrificans. The biotechnological potential ofM. aerodenitrificans described in the literature indicatesits ability for aerobic and anaerobic denitrification in wastetreatment technologies using bioreactors . 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DOI 10.1186/s12896-015-0214-0.Zhang L., Zhao T., Wang Q., Li L., Shen T., Gao G. Bacterialcommunity composition in aquatic and sediment samples withspatiotemporal dynamics in large, shallow, eutrophic LakeChaohu, China. J. Freshw. Ecol. 2019;34(1):575-589. DOI10.1080/02705060.2019.1635536."} +{"text": "Cyanthillium cinereum is a member of the tribe Vernonieae from the family Compositae. The tribe was traditionally placed in the subfamily Cichorioideae, but is recently proposed to be placed in its own subfamily Vernonioideae. The complete chloroplast genome (cp genome) of the genus Cyanthillium is sequenced for the first time. The cp genome of C. cinereum is 152,750\u2009bp in length. It contained a large single copy (LSC) region , and small single copy (SSC) region , and two inverted repeats . Phylogenetic analysis of 20 species was conducted. C. cinereum and Gymnanthemum amygdalinum which are members of tribe Vernonieae nested outside of the monophyletic clade formed by members of subfamily Cichorioideae. The findings would be useful to understand the phylogeny of the genus Cyanthillium and the subfamily Vernonioideae. Cyanthillium cinereum (L.) H. Rob. (Robinson Vernonia cinerea (L.) Less. . The species is member of the tribe Vernonieae, also known as the \u201cEvil Tribe\u201d for its taxonomic complexity , no special permission is required. The voucher specimen with collector number T. Y. Siu 667 was deposited in the Shiu-Ying Hu Herbarium, School of Life Sciences, the Chinese University of Hong Kong .The species is characterized by having pale pink tubular florets, and ovate leaves with undulate margin according to the manufacturer\u2019s protocol. Extracted DNA was quantified using NanoDrop Lite . The DNA quality was checked by visualization of the DNA by 1% agarose gel electrophoresis. Illumina 150\u2009bp paired-end (PE) library was constructed and sequenced on the NovaSeq 6000 platform by Novogene Bioinformatics Technology Co., Ltd. . Poor-quality reads (Phred score < 33) were trimmed using CLC Assembly Cell package v5.1.1 .Total genomic DNA of Saussurea chabyoungsanica (NC_036677.1), and assembled into a complete chloroplast genome. Genome annotation was performed on the GeSeq platform by using complete cp genomes of Saussurea chabyoungsanica (NC_036677.1) and Saussurea japonica (NC_044738.1) as references. A few adjustments for protein-coding genes and start and stop codons were performed manually. The annotated genome was deposited in GenBank with the accession number OK040129.The reads were assembled into contigs using the CLC de novo assembler in CLC Assembly Cell package and SOAPdenovo v3.23 with default parameters. Gaps were filled by the Gapcloser module in SOAP package. The contigs were then aligned to the reference genome Cyanthillium cinereum was 152,750\u2009bp in length, containing a large single copy (LSC) region , small single copy (SSC) region , and two inverted repeats . The GC content was 37.71%. The cp genome contained 111 unique genes, including 80 protein-coding genes, 27 tRNA genes, and 4 rRNA genes.The cp genome of Cyanthillium cinereum, the cp genome was aligned with 18 sequences within Compositae, with Menyanthes trifoliata from the closely related family Menyanthaceae as an outgroup. The complete cp genomes were aligned using MAFFT 7.48 (Katoh et\u00a0al., Cyanthillium cinereum and Gymnanthemum amygdalinum which are members of tribe Vernonieae nested outside of the monophyletic clade formed by other members of subfamily Cichorioideae, which would support the separation of the tribe from the subfamily Cichorioideae. However, the two species from the tribe Vernonieae, now subfamily Vernonioideae, did not form a monophyletic clade. Further study is required to resolve the intergeneric relationship within the subfamily Vernonioideae and the taxonomic placement of the subfamily Vernonioideae.To investigate the taxonomic position of This research was conducted in accordance with the Legislation of Hong Kong Special Administrative Region. The sample collections did not cause any environmental problem.Conceptualization: T.Y.S., D.T.W.L., P.C.S. Methodology: T.Y.S., K.H.W, B.L.H.K, H.Y.W., G.W.C.B. Data analysis: T.Y.S., B.L.H.K, K.H.W. Writing\u2014original draft: T.Y.S. Writing\u2014review and editing: K.H.W, B.L.H.K, H.Y.W., G.W.C.B., D.T.W.L., P.C.S. Supervision: D.T.W.L., P.C.S."} +{"text": "Senegalia comprises 219 species distributed in tropical and subtropical regions of North and South America, Africa, Asia and Australia. Two sections are currently recognised within Senegalia and these are most readily distinguished by the differences in disposition of their cauline prickles, i.e. sect. Senegalia with prickles at or near leaf nodes and sect. Monacanthea with mostly internodal prickles. Previous phylogenetic studies, based primarily on small numbers of plastid DNA loci, found Senegalia to be monophyletic with two large subclades corresponding to the sections. Here, we present new phylogenomic evidence from 997 single-copy nuclear gene sequences for a small, but representative set of species. These new analyses show that Senegalia is non-monophyletic, but instead, forms a grade that is paraphyletic with respect to the remainder of the ingoid clade (i.e. Ingeae + Acacia s.s. + Acaciella), comprising two well-supported subclades most likely representing the same clades as found in previous phylogenetic studies of the genus and, interspersed between these, a third, moderately supported clade, comprising the genera Mariosousa, Pseudosenegalia and Parasenegalia. In marked contrast to the nuclear phylogeny, the two Senegalia clades are sister groups in the plastid phylogeny, based on analyses of 72 chloroplast genes, rendering the genus monophyletic, based on plastid data alone. We discuss this new evidence that Senegalia is non-monophyletic in relation to the marked cytonuclear discordance, high gene tree conflict and lack of resolution across this senegalioid grade and review the consistency of the key morphological characters distinguishing the two sections of Senegalia. We conclude that it is likely that Senegalia will need to be split into two (or possibly more) genera: a re-circumscribed Senegalia s.s. that corresponds to the existing Senegaliasect.Senegalia plus the S.ataxacantha group and a new genus corresponding to the remainder of sect. Monacanthea . However, re-delimiting Senegalia now would be premature given that the key morphological characters are not fully congruent with the two sections and pending denser phylogenetic sampling of taxa. A judiciously selected list of critical taxa is presented to facilitate future phylogenomic studies. Finally, we discuss the identity of Albizialeonardii, which is also placed in this senegalioid grade in these new phylogenomic analyses and place it in synonymy with Parasenegaliavogeliana. Senegalia Raf. was segregated from Acacia Mill. by Acaciella Britton & Rose, in their treatment of Acacia for the Flora of North America. However, despite this recognition by Senegalia was subsequently ignored (Acacia sensu lato (s.l.) as a broadly circumscribed pantropical genus persisted until the reclassification of Acacia by ignored and BentAcacia into three genera: Acacia sensu stricto (s.s.), Senegalia and Racosperma Mart. These genera corresponded to the three subgenera of Acacia s.l. recognised by Acacia (now Vachellia Wight & Arn.), subg. Aculeiferum Vassal and subg. Phyllodineae DC. , respectively. Although Pedley\u2019s classification was not immediately adopted, over the following two decades, a series of molecular and morphological phylogenetic analyses demonstrated that Acacia s.l. was polyphyletic and could not be sustained as a single genus of four small New World genera, namely Acaciella , while Acaciella is placed in the Calliandra clade sensu Calliandra Benth. and Afrocalliandra E.R. Souza & L.P. Queiroz and is not discussed further in this paper.nus e.g. . While tcaciella , Marioso Ebinger , Parasen Ebinger and Pseu Ebinger . These fprickles . Recent prickles have shoSenegalia today comprises 219 species (235 taxa) distributed pantropically and sect. Monacanthea Maslin . The monophyly of Senegalia was supported by recent phylogenetic analyses of plastid DNA sequences , it does represent a reasonable geo-taxonomic sampling of the group. The wider phylogeny showing the relationships of this senegalioid grade within the mimosoid clade P.J.H. Hurter and Senegaliasect.Monacanthea s.s. represented by S.ataxacantha (DC.) Kyal. & Boatwr. on the one hand represented by S.bahiensis (Benth.) Seigler & Ebinger, S.sakalava (Drake) Boatwr., S.borneensis (I.C. Nielsen) Maslin, Seigler & Ebinger and S.pentagona (Schumach. & Thonn.) Kyal. & Boatwr. on the other hand Seigler & Ebinger, Parasenegaliavisco (Lorentz ex Griseb.) Seigler & Ebinger and Pseudosenegaliafeddeana (Harms) Seigler & Ebinger and form successive sister groups to the remainder of the ingoid clade sensu Senegalia is not monophyletic how to define paraphyly vs. monophyly when there is pronounced cytonuclear discordance indicative of incomplete lineage sorting or reticulation and (2) is it justified to divide a genus into multiple segregate genera when the relationships amongst the constituent lineages are unresolved ? With respect to the first question, we suggest that, given the propensity for plastid capture or introgression in plants .The phylogenomic evidence, discussed here, shows that Senegalia \u2013 Fig. Monacanthea \u2013 Fig. Senegalia \u2013 Fig. Monacanthea \u2013 Fig. Senegalia \u2013 Fig. Monacanthea \u2013 Fig. Senegalia, while they are absent in the three allied genera in the New World, namely Mariosousa, Parasenegalia and Pseudosenegalia Kyal. & Boatwr. was described as unarmed, but this species was known only from the type, which could be anomalous and examination of additional material is needed to verify this observation. Second, Senegaliacaffra (Thubb.) P.H. Hurter & Mabb. was described as rarely having a few scattered prickles on the internodes, in addition to the pair located at the nodes. Flowers in 95% of species of sect. Senegalia are aggregated in spikes (containing sessile flowers) or occasionally spiciform racemes (i.e. spikes with pedicellate flowers), while globose or sometimes oblongoid heads occur in only two African taxa, S.densispina (Thulin) Kyal. & Boatwr. and S.melliferasubsp.detinens (Burch.) Kyal. & Boatwr. In the majority of species of sect. Senegalia, the inflorescences are axillary, but occasionally they are arranged in racemes or panicles, e.g. S.burkei (Benth.) Kyal. & Boatwr. and S.caffra from Africa. Unlike many species of sect. Monacanthea, lianas are never found amongst the species of sect. Senegalia distributed in the Americas , Africa, Asia and Australia , there is some variation in armature that appears to reduce the discriminating value of this character in that region and which warrants further investigation. Of the 99 species New World species of Senegaliasect.Monacanthea p.p. there are 28 species that possess nodal prickles, at least some of the time. For example, it is not uncommon to find specimens, especially amongst species in the informal S.berlandieri species-group and S.monacantha (Willd.) Seigler & Ebinger from the informal S.monacantha species-group, which have 1\u20133 prickles associated with some or most nodes, in addition to those on the internodes. Furthermore, the following three species have one or two prickles associated with some nodes, but none on the internodes, namely, S.emilioana Seigler & Ebinger, S.gilliesii (Steud.) Seigler & Ebinger Britton & Rose species-group.The much larger pantropical sect. lia Fig. , Table 1.p. Fig. and nodalia Fig. . Howeverger Fig. and S.suMonacanthea p.p. from sect. Senegalia, but again, some New World species differ somewhat from those elsewhere. In the Afro-Asian region where the two sections co-occur, 92% of sect. Monacanthea p.p. species possess globose/oblongoid heads . Of the five sect. Monacanthea p.p. species from this region that possess spikes, three are from Madagascar and two are from Southeast and East Asia . In the New World , there is a stronger bias towards spicate inflorescences within sect. Monacanthea p.p. where 26 species (representing 27% of the species from the region) possess spikes . Globally, a higher percentage of sect. Monacanthea p.p. species also has inflorescences arranged in terminal racemes or panicles than those with inflorescences arising from the axils of leaves, contrasting with sect. Senegalia where most species have axillary inflorescences. In sect. Monacanthea p.p., lianas are relatively common is a useful character for distinguishing sect. ads Fig. , contraskes Fig. , while 7kes Fig. . It is nmon Fig. , whereasubs Fig. , especiaSenegaliaataxacantha and its three relatives, S.macrostachya (Rchb. ex DC.) Kyal. & Boatwr., S.chariessa (Milne-Redh.) Kyal. & Boatwr. and S.eriocarpa (Brenan) Kyal. & Boatwr. have consistently been placed in the same clade as sect. Senegalia in all phylogenetic studies that included one or other of these species , while the remainder of the section is referred to as sect. Monacanthea p.p. However, unlike species of sect. Senegalia that have prickles located at or near the leaf nodes, these four African species , similar to the majority of species of sect. Monacanthea p.p. Indeed, Acaciaataxacantha as the type of the section . These four species have flowers arranged in spikes . These intermediate characteristics of sect. Monacanthea s.s. are in line with their phylogenetic placement as either sister to sect. Senegalia or sister to the rest of sect. Senegalia minus S.catechu (L.f.) P.J.H. Hurter & Mabb. . The name ManganaroaS.monacantha, while placed in sect. Monacanthea p.p., has not so far been included in any phylogenetic study. In any case, it is clear that this discordant combination of internodal prickles and spicate inflorescences undermines the potential of these two characters to straightforwardly diagnose the two major clades of Senegalia , reveals that these collections show a suite of vegetative characters that are consistent with those of Parasenegaliavogeliana (Steud.) Seigler & Ebinger: there are no prickles on the branches; the petiolar nectary has the same position and shape; similar leaflet shape, size, apex, base and veins; number of pinnae pairs (about 4) and number of leaflets per pinna (about 10). This is in line with the determination of the US holotype as Lysilomavogelianum (Steud.) Stehl\u00e9, which is a homotypic synonym of Parasenegaliavogeliana in the phylogenetic analysis of The phylogenetic placement of ies Fig. raises qogeliana and withdii Fig. , supportParasenegaliavogeliana (Steud.) Seigler & Ebinger in Seigler et al., Novon 25(2): 197\u2013199, fig. 9. 2017.Acaciaambigua Vogel, Linnaea 10: 600\u2013601. 1836, nom. illeg., non Acaciaambigua Hoffmanns., Zweit. & Dritt. Nacht. Verz. Pfl.-Kult., [3rd addendum] 15. 1826. Type: B\u2020.Acaciavogeliana Steud., Nomencl. Bot. [Steudel], ed. 2,1: 9. [Aug.] 1840, replacement name for Acaciaambigua Vogel, Type: Based on Acaciaambigua Vogel.Senegaliavogeliana (Steud.) Britton & Rose, N. Amer. Fl. 23(2): 116. [25 Sep.] 1928. Type: Based on Acaciaambigua Vogel.Lysilomavogelianum (Steud.) Stehle, Bull. Mus. Natl. Hist. Nat., s\u00e9r. 2, 18(2): 193\u2013194. 1946. Type: Based on Acaciaambigua Vogel.Type material. Haiti. Santo Domingo: Plaine pr\u00e9s de Port-au-Prince, Ramuli partem cl. Ehrenberg misit tantum summam; 1828\u20131839, C.A. Ehrenberg 274 + photo of holotype, NY. Paratype: Haiti. Dept. Artibonite: Dubedou (de Gonaives), 20 km al N. de Gonaives en la carretera a Port-de Paix, zona arida; 130 m alt.; 8 Jun 1985; [young bud]; T. Zanoni et al. 34986 .Senegalia comprises two, robustly supported clades, which largely correspond to sect. Senegalia and sect. Monacanthea, but with the exception of the S.ataxacantha group (sect. Monacanthea s.s.) which aligns with sect. Senegalia. The recent phylogenomic analyses, discussed here, show that these two clades are not sister groups and that Senegalia is non-monophyletic supporting the possible recognition of these clades as separate genera, based on nuclear data. We anticipate that Senegalia will indeed need to be re-classified to reflect this non-monophyly. However, it is also clear that the key morphological traits distinguishing these two clades, namely, armature and, to a lesser extent, inflorescence shape, are not totally consistent across the majority of species within these clades. The most notable inconsistency presently known is the small African S.ataxacantha group that is morphologically discordant with the phylogenetic evidence and whether this group is most appropriately treated as a separate genus or retained within the genus Senegalia remains to be decided. Given that only about 75 of the total 219 species of Senegalia have so far been included in phylogenies (with only six in the recent phylogenomic studies) and that a number of morphologically anomalous species have not yet been sampled for molecular data, it is clear that splitting Senegalia at this point would be premature, especially given the nomenclatural repercussions involving name changes for 164 species on four continents. More species of the two clades of Senegalia and the allied genera Mariosousa, Parasenegalia and Pseudosenegalia need to be sequenced and an in-depth investigation of possible reticulate patterns, including with the use of phylogenetic network analysis, should be carried out before any decisions regarding formal taxonomic rearrangements are made. Consequently, below we provide a list of critical taxa for future sequencing, ideally to be carried out using the Mimobaits nuclear gene set of All phylogenetic studies have shown that Senegalia. In addition, denser sampling of taxa across the allied genera Mariosousa, Parasenegalia and Pseudosenegalia is needed.The following species are suggested for inclusion in future phylogenomic studies to achieve taxon sampling that is geographically, morphologically and taxonomically representative of Mariosousa species:M.centralis (Britton & Rose) Seigler & Ebinger,M.coulteri (Benth.) Seigler & Ebinger.Parasenegalia species:P.miersii (Benth.) Seigler & Ebinger,P.muricata (L.) Seigler & Ebinger,P.rurrenabaqueana (Rusby) Seigler & Ebinger,P.vogeliana (Steud.) Seigler & Ebinger.Pseudosenegaliariograndensis (Atahuachi & L. Rico) Seigler & Ebinger.Senegalia species:Monacanthea p.p. species with globose or oblongoid heads):S.brevispica subsp.brevispica (Harms) Seigler & Ebinger,S.schweinfurthii (Brenan & Exell) Seigler & Ebinger (either variety).Africa (sect.Monacanthea s.s.):Ataxacantha species-group:S.eriocarpa,S.chariessa,S.macrostachya.Africa :S.burkei orS.caffra (inflorescences racemes or panicles),S.densispina (heads globose),S.erubescens (Welw. ex Oliv.) Kyal. & Boatwr.,S.laeta (R. Br. ex Benth.) Seigler & Ebinger orS.rovumae (Oliv.) Kyal. & Boatwr. ,S.senegal (L.) Britton (any variety),S.mellifera (Vahl) Seigler & Ebinger.Africa (sect.Monacanthea p.p.):Amazonica species-group:S.amazonica (Benth.) Seigler & Ebinger,S.serra (Benth.) Seigler & Ebinger;Berlandieri species-group:S.berlandieri (Benth.) Britton & Rose,S.bonariensis (Gillies ex Hook. & Arn.) Seigler & Ebinger,S.gaumeri (S.F. Blake) Britton & Rose orS.langsdorffii (Benth.) Seigler & Ebinger,S.kelloggiana (A.M. Carter & Rudd) C.E. Glass & Seigler,S.paganuccii Seigler, Ebinger & P.G. Ribeiro,S.picachensis (Brandegee) Britton & Rose orS.interior Britton & Rose;Greggii species-group:S.emilioana,S.gilliesii,S.greggii,S.occidentalis (Rose) Britton & Rose,S.subsessilis;Martiusiana species-group:S.martiusiana (Steud.) Seigler & Ebinger;Monacantha species-group:S.monacantha;Pedicellata species-group:S.pedicellata (Benth.) Seigler & Ebinger;Polyphylla species-group:S.polyphylla (DC.) Britton & Rose;Riparia species-group:S.riparia (Kunth) Britton & Rose;Tamarindifolia species-group:S.tamarindifolia (L.) Britton & Rose;Tenuifolia species-group: S.mirandae (L. Rico) Seigler & Ebinger,S.tenuifolia (L.) Britton & Rose.Unplaced in any group:S.kallunkiae (J.W. Grimes & Barneby) Seigler & Ebinger,S.piptadenioides (G.P. Lewis) Seigler & Ebinger,S.ricoae (Bocage & Miotto) L.P. Queiroz ,S.weberbaueri (Harms) Seigler & Ebinger.Americas (sect.Monacanthea p.p.):Caesia species-group:S.caesia (L.) Maslin, Seigler & Ebinger;Hainanensis species-group:S.hainanensis (Hayata) H. Sun and/orS.pluricapitata (Steud. ex Benth.) Maslin, Seigler & Ebinger;Pennata species-group:S.kerrii (I.C. Nielsen) Maslin, B.C. Ho, H. Sun & L. Bai,S.pennata (L.) Maslin (either or both subspecies) orS.megaladena (Desv.) Maslin, Seigler & Ebinger (either subspecies);Rugata species-group:S.rugata (Lam.) Britton & Rose;Teniana species-group:S.kunmingensis (C. Chen & H. Sun) Maslin, B.C.Ho, H.Sun & L.Bai orS.prominens Maslin, B.C. Ho, H. Sun & L. Bai,S.yunnanensis;Unplaced in any group:S.donnaiensis,S.kostermansii (I.C. Nielsen) Maslin, Seigler & Ebinger,S.kekapur (I.C. Nielsen) Maslin, Seigler & Ebinger,S.thailandica (I.C. Nielsen) Maslin, Seigler & Ebinger.Asia : S.catechu,S.modesta P.J.H. Hurter.Asia: (sect.Monacanthea p.p. species with spikes):S.menabeensis.Madagascar (sect."} +{"text": "Drosophila. Advanced Genetics. 2020; 1:e10026. https://doi.org/10.1002/ggn2.10026Tsurumi, A, Li, WX. Aging mechanisms\u2014A perspective mostly from In the originally published version of this article, Shriners Hospitals Research Funding was misattributed to Willis Li in the Acknowledgments section. The correct funding recipient is Amy Tsurumi. The correct acknowledgments appear below. The publisher regrets the error."} +{"text": "Candidatus Culexarchaeia\u201d, named after the Culex Basin in Yellowstone National Park. Culexarchaeia harbor distinct sets of proteins involved in key cellular processes that are either phylogenetically divergent or are absent from other closely related TACK lineages, with a particular divergence in cell division and cytoskeletal proteins. Metabolic reconstruction revealed that Culexarchaeia have the capacity to metabolize a wide variety of organic and inorganic substrates. Notably, Culexarchaeia encode a unique modular, membrane associated, and energy conserving [NiFe]-hydrogenase complex that potentially interacts with heterodisulfide reductase (Hdr) subunits. Comparison of this [NiFe]-hydrogenase complex with similar complexes from other archaea suggests that interactions between membrane associated [NiFe]-hydrogenases and Hdr may be more widespread than previously appreciated in both methanogenic and non-methanogenic lifestyles. The analysis of Culexarchaeia further expands our understanding of the phylogenetic and functional diversity of lineages within the TACK superphylum and the ecology, physiology, and evolution of these organisms in extreme environments.Geothermal environments, including terrestrial hot springs and deep-sea hydrothermal sediments, often contain many poorly understood lineages of archaea. Here, we recovered ten metagenome-assembled genomes (MAGs) from geothermal sediments and propose that they constitute a new archaeal class within the TACK superphylum, \u201c Euryarchaeota, and TACK archaea\u2014and it is likely that high-ranking lineages are yet to be discovered 14], and eviously and are The 16S rRNA gene sequences encoded in Culexarchaeia MAGs were used in BLASTn searches to screen NCBI and IMG databases for related sequences. Culexarchaeia 16S rRNA sequences were aligned against reference archaeal 16S rRNA sequences and masked using SSU-ALIGN , which pCatalytic subunits of group 4 [NiFe]-hydrogenases encoded in Culexarchaeia MAGs were subjected to phylogenetic analysis along with a set of reference sequences extracted from the HydDB . Amino aReference amino acid sequences from within the tubulin superfamily \u201338 were Initial analysis of the metabolic potential of the Culexarchaeia MAGs was performed using the annotations provided by the IMG/M database which uses KEGG, COG, pfam, and enzyme ID databases . Manual Sulfolobales, Desulfurococcales, and Thermoproteales were screened for the presence and absence of key cellular machinery proteins, identified in previous work -hydrogenase (MvhADG) may form a bifurcating complex with HdrABC, as found in other diverse archaea, which allows for the oxidation of H2 to be coupled to the reduction of ferredoxin and a disulfide compound -hydrogenase that may couple the reversible oxidation of NADPH to the reduction of protons to evolve H2 . Characte to H2S , 86. Thu2 to the reduction of the heterodisulfide CoM-S-S-CoB and translocation of ions outside the cell, which would allow for energy conservation during methylotrophic methanogenesis -hydrogenase complex termed Ehd) that were co-located with genes encoding heterodisulfide reductase subunits (HdrBC) and an ion antiporter subunit Fig.\u00a04BB4B, F. Te-hydrogeogenesis . A similhd that wogenesis , and a gs >65\u2009\u00b0C , which ac growth .Fig. 4Mo2 oxidation could also be coupled to the reduction of an unknown disulfide (via HdrB) that could be generated through the activity of the HdrA2B2C2 or HdrABC-MvhADG bifurcating complexes. The identity of this disulfide is unknown, but Culexarchaeia lack a full biosynthetic pathway for CoM and CoB, which suggests that an alternative disulfide may be used. The GcvH protein, encoded within the Ehe gene cluster, typically functions in the glycine cleavage pathway to coordinate a disulfide containing lipoyl moiety -hydrogenases in the metabolism of these organisms.Candidatus Culexarchaeia\u201d, that is most closely related to the proposed methylotrophic and methanogenic lineage \u201cCa. Methanomethylicia\u201d (Verstraetearchaeota) [2, CO, S0) substrates. Notably, the potential for anaerobic non-methanogenic methylotrophy and cyanophycin degradation, which to our current knowledge are not widespread among archaea, suggests that Culexarchaeia may be important in cycling these compounds in extreme environments and that these putative functions could be exploited in future cultivation attempts. The biogeographic distribution of terrestrial and marine Culexarchaeia indicates that they are found in high temperature (>50\u2009\u00b0C) and circumneutral to slightly acidic (pH 5.4\u20137.8) environments. The capacity to metabolize many organic and inorganic substrates suggests that they could be important in the biogeochemical cycles of hydrogen, carbon, and sulfur within these diverse geothermal habitats, even at low relative abundances. The metabolic versatility encoded by Culexarchaeia could imply adaptations to changing nutrient conditions present in dynamic geothermal systems, because they could access a wide variety of compounds for their carbon and energy needs. Additionally, Culexarchaeia expand the diversity of cell division and cytoskeletal proteins in the TACK archaea, as they encode FtsZ-like, CdvBC, crenactin, and arcadin proteins. Future studies will need to determine how these diverse cell division and cytoskeletal proteins contribute to cell cycle and maintenance processes in Culexarchaeia, and could aid in understanding other lineages that similarly encode multiple division and cytoskeletal systems , Heimdallarchaeota, and Odinarchaeota).Here we report on a new archaeal class within the TACK superphylum, \u201cchaeota) . In cont2/CO2 [2/CO2 utilizing Nezhaarchaeia . If methanogenesis was the metabolism present in the last common ancestor of these lineages, Culexarchaeia will aid in understanding shifts from methanogenic to non-methanogenic lifestyles in the TACK archaea. This type of transition is considered to have been an important process in archaeal evolution and is partially responsible for the observed patchwork distribution of MCR-encoding lineages [The phylogenetic placement of Culexarchaeia aids in reconstructing the evolutionary history of TACK archaea. Particularly, their relatedness to the proposed methanogenic Methanomethylicia and Nezhaarchaeia, may provide insights into the evolutionary transitions between methanogenic and non-methanogenic lineages. Currently, the evolution of the WLP as well as the MCR and MTR complexes in the TACK archaea are not well understood, which precludes our understanding of the evolutionary history of methane metabolism and whether the last ancestral methanogen used methyl compounds or H2/CO2 , 48, 93.lineages , 94, 95.Following the recommendations by Chuvochina et al. 2019 , we assiCandidatus Culexarchaeia class nov.Cu.lex.ar.chae\u2019ia. N.L. neut. n. Culexarchaeales, type order of the class; L. -ia, ending to designate a class; N.L. fem. pl. n. Culexarchaeia, the Culexarchaeum class. The description is the same as for Candidatus Culexarchaeum gen. nov.Candidatus Culexarchaeales order nov.Cu.lex.ar.chae\u2019ales. N.L. neut. n. Culexarchaeaceae, type family of the order; L. -ales, ending to designate an order; N.L. fem. pl. n. Culexarchaeales, the Culexarchaeum order. The description is the same as for Candidatus Culexarchaeum gen. nov.Candidatus Culexarchaeaceae fam. nov.Cu.lex.ar.chae.ace\u2019ae. N.L. neut. n. Culexarchaeum, type genus of the family; L. -aceae ending to designate a family; N.L. fem. pl. n. Culexarchaeaceae, the Culexarchaeum family. The description is the same as for Candidatus Culexarchaeum gen. nov.Candidatus Culexarchaeum gen. nov.Cu.lex.ar.chae\u2019um N.L. neut. n. Culex, referring to the Culex Basin; N.L. neut. n. archaeum, an archaeon; N.L. neut. n. Culexarchaeum, archaeon of Culex, referring to the Culex Basin of Yellowstone National Park, where this lineage was discovered. The type species is Candidatus Culexarchaeum yellowstonense.Candidatus Culexarchaeum yellowstonense sp. nov.yel.low.ston.en\u2019se N.L. neut. adj. yellowstonense, from Yellowstone National Park. This uncultured lineage is represented by bin YNP-LCB-024-027, recovered from an unnamed hot spring in the Culex Basin of Yellowstone National Park. The bin has an estimated completeness of 97.2% and a contamination of 0.93% and contains 16S rRNA, 23S rRNA and 5S rRNA genes.Candidatus Culexarchaeum nevadense sp. nov.ne.va.den\u2019se N.L. neut. adj. nevadense, from Nevada. This uncultured lineage is represented by bin GBS-70-058, recovered from Great Boiling Springs in Nevada. The bin has an estimated completeness of 96.7% and a contamination of 0.07% and contains 16S rRNA, 23S rRNA, and 5S rRNA genes.Candidatus Culexarchaeum jinzeense sp. nov.jin.ze.en\u2019se N.L. neut. adj. jinzeense, from Jinze. Represented by bin JZ-bin-30, recovered from a geothermal well in Jinze, Yunnan Province, China). The bin has an estimated completeness of 96.7%, a contamination of 0%, and contains 16S rRNA, 23S rRNA, and 5S rRNA genes. For a justification for the reclassification of this previously published bin , please Candidatus Culexmicrobiaceae fam. nov.Cu.lex.mi.cro.bi.ace\u2019ae. N.L. neut. n. Culexmicrobium, type genus of the family; L. -aceae ending to designate a family; N.L. fem. pl. n. Culexmicrobiaceae, the Culexmicrobium family. The description is the same as for Candidatus Culexmicrobium gen. nov.Candidatus Culexmicrobium gen. nov.Cu.lex.mi.cro.bi.ace\u2019ae. N.L. neut. n. Culex, referring to the Culex Basin; N.L. neut. n. microbium, a microbe; N.L. neut. n. Culexmicrobium, microbe of Culex, referring to the Culex Basin of Yellowstone National Park, where this lineage was discovered. The type species is Candidatus Culexmicrobium cathedralensis.Candidatus Culexmicrobium cathedralense sp. nov.ca.the.dra.len\u2019se N.L. neut. adj. cathedralense, from Cathedral Hill, a deep-sea hydrothermal vent in Guaymas Basin. This uncultured lineage is represented by bin GB-1867-05, recovered from deep-sea hydrothermal sediment in Guaymas Basin in the Gulf of California . The bin has an estimated completeness of 99%, a contamination of 3.74%, and contains 16S rRNA, 23S rRNA and 5S rRNA genes.Candidatus Culexmicrobium thermophilum sp. nov.ther.mo.phil\u2019um N.L. neut. adj. thermophilum, heat-loving. This uncultured lineage is represented by bin GB-1845-036, recovered from deep-sea hydrothermal sediment in Guaymas Basin in the Gulf of California . The bin has an estimated completeness of 99%, a contamination of 3.74%, and contains 16S rRNA, 23S rRNA and 5S rRNA genes.Candidatus Culexmicrobium profundum sp. nov.pro.fund\u2019um N.L. neut. adj. profundum, deep. Represented by bin GB-1867-035, recovered from deep-sea hydrothermal sediment in Guaymas Basin in the Gulf of California . The bin has an estimated completeness of 96.7%, a contamination of 7.79%, and contains a 5S rRNA gene.Supplementary InformationSupplemental Files 1-8"} +{"text": "Uncomplicated acute appendicitis can be managed with non-operative (antibiotic) treatment, but laparoscopic appendicectomy remains the first-line management in the UK. During the COVID-19 pandemic the practice altered, with more patients offered antibiotics as treatment. A large-scale observational study was designed comparing operative and non-operative management of appendicitis. The aim of this study was to evaluate 90-day follow-up.A prospective, cohort study at 97 sites in the UK and Republic of Ireland included adult patients with a clinical or radiological diagnosis of appendicitis that either had surgery or non-operative management. Propensity score matching was conducted using age, sex, BMI, frailty, co-morbidity, Adult Appendicitis Score and C-reactive protein. Outcomes were 90-day treatment failure in the non-operative group, and in the matched groups 30-day complications, length of hospital stay (LOS) and total healthcare costs associated with each treatment.versus 3\u2009days, P\u2009<\u20090.001) were noted in the antibiotic management group. Accounting for interval appendicectomy rates, the mean total cost was \u20ac1034 lower per patient managed without surgery.A total of 3420 patients were recorded: 1402 (41 per cent) had initial antibiotic management and 2018 (59 per cent) had appendicectomy. At 90-day follow-up, antibiotics were successful in 80 per cent (1116) of cases. After propensity score matching (2444 patients), fewer overall complications (OR 0.36 (95 per cent c.i. 0.26 to 0.50)) and a shorter median LOS (2.5 This study found that antibiotics is an alternative first-line treatment for adult acute appendicitis and can lead to cost reductions. Adult appendicitis is the most common emergency general surgery condition worldwide, and is normally treated with laparoscopic appendicectomy despite evidence that it can be treated safely with antibiotics. The authors followed up patients who received operative treatment and non-operative treatment with antibiotics during the first wave of the COVID-19 pandemic. Non-operative management was associated with a shorter length of hospital stay, fewer complications and a significant health cost reduction compared with operative management. These concerns led to professional surgical societies recommending non-operative management with antibiotics over surgery as first-line management of acute appendicitisversus operative management at 90\u2009days.The collaborative\u2019s previous publication on the first 500 adult patients confirmed a significant shift in practice towards non-operative management of acute appendicitis and a higher number of CT scans (71 per cent) performed to aid diagnosis during the pandemicEthical approval was not required as the study collected routine, anonymized data and no clinical care was influenced.A prospective, multicentre study in the UK and the Republic of Ireland on patients aged at least 18 years diagnosed either clinically and/or radiologically with acute appendicitis in a secondary care setting was carried out. The patients were managed initially either with antibiotic (non-operative) or operative management. Data was collected from patients presenting from the date of the UK Government COVID-19 lockdown on 23 March 2020 (28 March 2020 in the Republic of Ireland) until 23 June 2020. Study registration was overseen by the local principal investigator at each site as either a clinical audit or service evaluation. This observational study was reported according to STROBE guidelines for observational studies, where appropriateAny hospital in the UK or Republic of Ireland providing emergency care for patients diagnosed with acute appendicitis could participate. The protocol was publishedwww.project-redcap.org)Local teams screened patients presenting with abdominal pain to identify patients eligible for inclusion. Once screened, collaborators entered anonymized data of patients meeting inclusion criteria to Research Electronic Data Capture .Admission variables were recorded for all patients including demographic data, frailty, co-morbidities, patient observations, duration of symptoms and blood inflammatory markers. Sites were asked to calculate an Adult Appendicitis Score (AAS) for each patient using an online calculator , death, rate of hospital reattendance, operations, interventional radiology (IR) drain placement, and admission to critical care (level 2 (high dependency unit) or 3 (intensive care unit)), 30-day complication rate and total costs. Operative details were recorded including surgical approach, duration of operation, procedure, surgical findings and histology.Patient demographics and outcomes were analysed by intention to treat by initial operative or non-operative management. Failure of non-operative management was recorded as management changing from antibiotics to surgery at least 2\u2009days after initial assessment. Patients requiring IR drainage on initial presentation were excluded from the main analysis as initial management was neither non-operative nor operative.Random number generation was used to select 15 per cent of patients entered into the database for data validation. Sites were asked to nominate an independent team member to collect data for a predetermined 25 per cent of data points for these randomly selected patients. These data were analysed centrally against the database and generated an overall data validation percentage of 98.1 per cent. Sites with data validation below 95 per cent were excluded from the analysis.U and Fisher\u2019s exact test as appropriate. Standardized differences (SD) are presented to show the differences between groups in baseline characteristics, with values of greater than 0.1 regarded as demonstrating imbalance between the groupsDue to missing data, all outcome proportions were reported as the number of events/total patients with data. Descriptive data were reported as median (i.q.r.) or rates as appropriate. Differences in demographics between the non-operative and operative groups were analysed using Mann\u2013Whitney www.stata.com). The user-written commands psmatch2 and stddiff were used.In order to reduce the effects of selection bias in this non-randomized cohort, propensity score matching was performed using a probit model for the following variables: age, sex, frailty status, Adult Appendicitis ScoreThe cost analysis undertook a time horizon of 90\u2009days, and was undertaken from the hospital perspective. The costs included were those pertaining to the index hospital admission, and any subsequent readmissions. Resource use categories were defined a priori and include those where differences between groups are likely to drive incremental costs. These are the duration of hospital admission including days in critical care and ward, duration and choice of surgical approach (open or laparoscopic), the use of antibiotics, the use of imaging and any subsequent readmissions. Total costs at 90\u2009days were calculated by combining resource-use data at the patient level with unit costs at 2018\u20132019 prices in pounds sterling, reported in Euros at a conversion rate of 1:1.16. The results were subjected to extensive sensitivity analyses, including the potential for unmeasured confounding and the approach taken in the unit costs analysis. A detailed breakdown of the costings used are available in Fig. 1): 48 per cent (1643 patients) were female; median age 36 (i.q.r. 26\u201352) \u2009years. Overall COVID-19 positivity was low at 1 per cent (32 patients).A total of 3420 patients were included in the analysis (Acute appendicitis was treated first line with non-operative management in 41 per cent (1402 patients) and operative management in 59 per cent (2018 patients). Laparoscopic appendicectomy was performed in 65 per cent (1298 patients), laparoscopic converted to open in 3 per cent (61 patients) and open appendicectomy in 32 per cent (644 patients). At 90\u2009days\u2019 follow-up, 80 per cent (1116 of 1402) of the non-operative group had avoided operative intervention. Baseline characteristics by group are shown in P\u2009<\u20090.001). Blood inflammatory markers were significantly different between the two groups; the median CRP on admission of those in the operative group was 49 mg/L (i.q.r. 14\u2013127) and in the non-operative group was 33 mg/L (i.q.r. 8\u201398) (P\u2009<\u20090.001), and white cell count was 13.9 109/L (i.q.r. 11.1\u201316.8) and 12.5 109/L (i.q.r. 9.8\u201315.6) respectively (P\u2009<\u20090.001).Patients with laboratory-confirmed COVID-19 infection on admission were more likely to undergo non-operative management: 11 patients in the operative group and 21 in the non-operative management group . CT was performed in 70 per cent of patients in both groups, with a faecolith present in 30 per cent (713 patients) of all patients. Of those found to have a faecolith, 73 per cent (523 patients) were managed operatively and 27 per cent (190 patients) were initially managed non-operatively (P\u2009<\u20090.001).Patients who had non-operative management were more likely to have an ultrasound scan performed than those in the operative group . The median time interval to change of management from non-operative to operative management was 2 (i.q.r. 2\u20137) days. The majority of decisions to change management strategy occurred in the first week (76 per cent), with 80 per cent occurring in the first 2\u2009weeks. Operative procedures performed were appendicectomy , right hemicolectomy with anastomosis , washout and drain and other with missing data for 5 patients (2 per cent) (P\u2009=\u20090.601).Non-operative management was unsuccessful leading to surgery in 20 per cent (286) of patients; 60 per cent (170 patients) had a laparoscopic approach, 35 per cent (98 patients) open and 5 per cent (13 patients) had a laparoscopic converted to open procedure (P\u2009=\u20090.087). The presence of a faecolith was associated with a higher rate of perforated appendicitis and gangrenous appendicitis at operation when compared with patients who did not have a faecolith: 47 and 21 per cent versus 20 and 7 per cent respectively.More than a quarter of patients that had unsuccessful non-operative management did not have a CT . Of those that did, 91 per cent (186 of 204 patients) had CT features of appendicitis, meaning only 65 per cent of patients had confirmed appendicitis. Faecolithiasis was associated with unsuccessful non-operative management, present in 25 per cent (51 of 204) of patients with unsuccessful non-operative management and 18 per cent (139 of 777) of patients with successful non-operative management , chronic or previous appendicitis in 3 per cent (7 of 277), malignancy in 1 per cent (4 of 277), neuroendocrine tumour in 1 per cent (4 of 277), normal in 6 per cent (18 patients) and \u2018other\u2019 in 3 per cent (9 patients). The LOS in patients who had unsuccessful non-operative management was a median of 4 (i.q.r. 3\u20136) days. The outcomes of these patients are shown in versus 3 (i.q.r. 2\u20134) days, P\u2009<\u20090.001). There was no difference between operative and non-operative groups for risk of serious complications, including myocardial infarctions, venous thromboembolism, unplanned critical care admission or death. Hospital-acquired pneumonia , wound infection and intra-abdominal collections were significantly lower in the non-operative group as opposed to matched operative management patients, giving a lower overall risk of complications . There was an increase in unplanned reattendances and readmissions in the non-operative group .A comparison of propensity score-matched patients (1222 matched patients in each group by co-variables listed in P\u2009=\u20090.001). The majority of normal appendicectomies were performed in women: 72 per cent (36 of 50) in the operative group and 78 per cent (14 of 18) in the unsuccessful non-operative group.Overall, the negative appendicectomy rate was 3 per cent (68 of 2274 patients): the appendix was histologically normal in 3 per cent (50 of 1994 patients) of those having initial operative management and 6 per cent (18 of 280 patients) of those who had unsuccessful non-operative management , that is a saving of that amount. The results were robust to alternative assumptions made in the sensitivity analyses, including the potential for unmeasured confounding or the approach taken in the unit cost calculation ,There were fewer complications and a shorter LOS in the non-operative group, a finding paralleled in other studies and maintained in those which report long-term follow-up,Even accounting for those who required interval appendicectomy, the average cost per patient was lower in the non-operative group with a mean reduction of \u2013\u20ac1034 (95 per cent c.i. \u2013\u20ac1201 to \u2212\u20ac865). These findings are consistent with other cost-analysis studies, although previous cost-analysis comparison was against open appendicectomy,Current guidelines recommend that a faecolith on imaging should be treated with surgery,Potential missed appendiceal malignancy is a clinical concern of non-operative management. This study found four cases of malignancy and three neuroendocrine tumours in the initial non-operative management group, and an overall rate of malignancy of 1.3 per cent, consistent with the population reported incidence of 0.5\u20131.7 per centversus 18 per cent of patients presenting with right iliac fossa pain in 2019)versus 20 per cent previously reported by the RIFT Study Group),In addition to providing assessment of potential markers of malignancy, CT scanning is sensitive for diagnosing appendicitisFollowing the landmark Montgomery UK Supreme Court ruling in 2015, the concept of informed consent has been re-evaluatedAs an observational study, there was no standardized antibiotic protocol and the decision to proceed with surgery was at the clinician\u2019s discretion. There is inherent bias when implementing any novel management, and it is challenging to capture changes that result from a different consultant taking over the patient\u2019s care, therefore there is the possibility of residual confounding. A large proportion of patients in the antibiotic group were diagnosed clinically, meaning that a presumed diagnosis of appendicitis was given to some patients. This could be a confounder for how many patients had truly unsuccessful non-operative management, particularly those with normal appendix histology. CT was not used universally as in previous RCTs. This is a strength as resource constraints in the National Health Service would probably prevent universal CT scanning if non-operative management were adopted in the future. However, this may have contributed to the 6 per cent negative appendicectomy rate in the group managed non-operatively. ; M. Creanga; A. Shafi; J. Law; M. Elniel; M. Walley; S. Ayyar , ; J. Cornish; N. Reeves; N. Mowbray; I. Mayo; M. Shinkwin ; E. Chohda; W. McCaughran; E. Beck; S. Garikipati ; B. E. Lovett; F. Alkistawi; S. Franklin; C. Hadjitoffi; A. Uddin ; P. K. Patel; S. Handa; J. Parker; D. Littlehales ; A. P. Belgaumkar; B. Oyewole; P. Narayan; Z. Elahi; A. Gaukroger ; D. F. J. Dunne; G. E. Nita; R. D. Baron; D. Sochorova; P. Szatmary; S. A. K. Gahunia; A. J. Thomas; K. S. Mann ; M. McFall; N. Farkas; H. Siddig ; J. Camilleri-Brennan; D. Rutherford; M. Wilson; E. Massie; K. McGivern; J. McGuckin; C. McKee ; S. Marinos-Kouris; E. Gammeri; N. Patel; G. Cillo; A. J. Baldwin; T. Magro ; K. Krishna; J. Olivier; N. Anyaugo; K. Philip ; L. Pearce; A. Al-Amin; M. Thomas; I. Anderson; R. Clark ; M. Basamh; S. M. Navaratnam; A. Saunt; B. Bekhyat Karki; H. Jeong; B. Singh; A. Rajendirin; K. Boyle; S. Fahmy; J. H. Couch; H. Z. Butt ; G. Tierney; J. N. Lund; H. Javanmard-Emamghissi; B. Doleman; C. Hope; A. Gowda; D. Photiou; F. Malcolm; P. Daliya; N. Rye; Z. Chia ; F. Anis ; P. Thomas; T. Urbonas; D. Centea; N. Husain ; S. Moug; A. Ingham; N. Galbraith ; R. Alexander; C. Bisset ; R. Clifford; L. Dickerson ; S. Lockwood; J. Johnston ; R. Guy; T. Majeed; R. Young; S. Shamim; M. Mesri ; R. Date; M. P. Chaudhury; G. Zambas ; R. Patel; S. Lewis; A. T. Eigbadon; D. Thakrar; E. Karamitsou; Y. Oyeyipo; U. Nadeem; S. Ndlovu; A. Fanshawe ; N. Henderson; C. Payne; D. Porter ; A. Brooks; R. X. N. Lee; J. Jackman; A. J. Morton; O. Ebunoluwa Oyende; D. Worku; A. Koh; T. Kanani; J. Blackwell; M. Shaw; C. Lloyd-Lewis; L. Blackburn; A. Adiamah ; S. Shaikh; M. Ghazanfar; M. Elhusseini; A. Abdelhamid; J. Eley; A. Nassar ; R. Nunn; A. Gales; E. Farinella; Z. Mahmood; T. Policastro ; N. M. Bagnall; U. Blyth ; R. J. McGregor; D. Damaskos; M. Drogouti; Z. Tuharska ; J. Davies; J. M. Bennett; R. Antakia; J. R. O\u2019Neill; R. H. Hardwick; N. Fearnhead; A. Xanthis; F. Georgiades; V. Hudson; J. Ashcroft; A. A. Singh ; S. M. U. Kabir; H. Huan; M. Sugrue ; M. Riera; J. Chang; A. Omosebi; E. Rigby; L. Kim; S. Ali; Z. Gates; H. Alasa; J. Y. N. Bo; A. Gangwar ; L. Osborne; B. Perakath ; M. Chandarana; M. Galea; A. Luhmann ; O. Ryska ; F. Searight; C. McCoss; B. Weber ; M. Sallam; R. Patel; M. Bignell; G. Bond-Smith; C. Lewis ; G. Williams; H. Whewell; L. Smith; R. Ooi; A. Powell-Chandler; A. M. Tang ; S. K. Richards; D. B. Thompson; R. Cross ; J. van Dellen; V. Alberto; S. Shirazi; H. Arang; N. Rahman ; E. Monaghan; K. Dodds; O. Babalola; P. Airhunmwunde; C. Chinaka ; I. Wijetunga; T. Kidd; K. Nambiar; C. E. Ng; T. Collier; B. Ibrahim; K. Khan ; K. Sriskandarajah; T. Pelly; J. Vance-Daniel ; P. Nastro; A. Khan; O. Ekowo; A. Devadoss ; P. D. Rao; K. Bateman; A. Gavrila ; E. Hannan; D. Winter; S. Martin; R. Kennelly; A. Hanly ; M. I. Aslam; V. Amin; R. Wilkins; S. Zafar; C. Konstantinou; S. Mcdonald; A. Baker; A. Fardie ; A. Hill; J. De Marchi; S. O'Grady ; G. Faulkner; H. Sekhar; M. Martinez-Iglesias; C. Alexander; E. Lawrence; S. Argyropoulos ; G. Williams; S. Bhasin ; M. Paduraru; K. Pawelec; S. Bylapudi ; H. Byrne; E. R. Da Silva Bento; F. Zahari; F. Roslan; M. Rao ; S. Hudson-Phillips; C. Kenington; S. Tellman; P. Abraham; A. Dhillon; Z. Vinnicombe ; M. Giles; M. Abbakar; N. Khadem; E. Buckley; L. Macdonald; J. Norman; R. Bond ; T. White; T. Gana; S. Kotecha; S. Rajain ; S. Ahmad; B. Wadham; L. Hancock ; A. Liyanage; I. Dorrington; A. Mian; R. Y. Satchidanand; C. Weerasinghe ; K. J. Etherson; H. Hidayat; M. Bhandari; A. Agarwal ; J. Sagar; S. Kudchadkar; A. Ghosh; N. Cirocchi; A. Rai; O. AlHabsha; S. S. Mujtaba ; F. Ejtehadi; I. Warrag; B. Ivanov; J. Refson; C. Boateng ; R. Madani; M. M. Buhsk; D. Kesharwani; L. Kumar; V. Prakash; S. Zulfiqar; A. Jayakumar ; A. Payne; C. Davies ; R. Buhain; D. Osilli; T. Rashid; I. Elzayat ; V. Kanakala; E. J. Nevins; A. Madhavan; E. Oates; K. France; S. Cowie ; J. Bowen; Y.-J. Nam; M. Bradbury; V. Mitchell ; S. M. Mirza; M. M. Raiz; E. Weatherstone; R. Wilson ; K. Sasapu; M. M. A. Rahman; E. Chan; K. Y. Ko; M. Sharman ; K. Thiruppathy; J. Hodgkinson; R. Chadha; T. Pilpel; J. Dale ; N. Carter; A. Botros; I. Bondoqa; S. Sandabah; K. Sherwood ; R. Harries; L. Hurt; R. Egan; L. Gauntlett; V. Bevan ; M. Vipond; P. Ireland; S. Granger; R. Preece ; D. Frith; J. Eves; A. Abuown ; J. Apollos; A. Macleod; N. Hemadasa ; C. McNaught; R. Mir; G. Cuthbert ; C. Valero ; D. Williams; M. Fakhrul-Aldeen; K. Willis; L. Kelly ; D. Lawes; L. Poynter; H. Knowles; S. Saeed; M. Shehata; I. Rafiq; M. Boshnaq; F. Ayoub ; A. Mcnair; D. J. Pournaras; S. Lawday; R. Martin; H. Cohen; M. Okocha ; K. Shalli; M. Chin; S. Joliffe ; F. Taylor; E. O. Argyriou; M. Dornseifer; E. Schembari; S. Surandran; L. Roberts; G. Kakaniaris ; E. Mallidis; G. Karagiannidis ; F. Youssef; A. Chan; C. Macutkiewicz; M. Davenport; S. Hodge; A. Clarke ; G. Branagan; R. Thakkar ; C. Harris ; C. Brown; M.-C. McGuigan ; I. Alam; K. Wang; F. Artemis .N. Kulkarni; I. Pereira; S. Barlow; S. Vanniasegaram ; F. Loro; N. S. Blencowe; B. E. Zucker; A. Tyler ; M. Hollyman; A. Kosti; M. Wijeyaratne; T. Badenoch ; S. Wheatstone; M. Jaffer; H. Gerretsen; R. Menon ; M. S. Sajid; L. Kennedy; A. Malik; A. Nada; K. Ray; M. Khan ; M. Varcada; F. Froghi; A. Khalil; D. Kyprianou ; N. Tewari; D. R. Sarma; M. Baig; S. Sood; E. Yu Wen Ng; V. Ng; T. Shortland; G. Marangoni; S. Khan; J. Ahmad ; S. Brown; C. Steele; A. Pannu ; E. Gemmill; H. Boyd-Carson; P. Herrod; S. Singh Shari; M. J. S. Mohammed; V. Narbad; N. Hanbali; A. Kushairi ; M. A. Mathew; C. Downey; A. Alamassi ; T. Wheatley; K. Emslie; B. Alcocer; S. Lau ; R. Morgan; T. Gala; S. Ibrahim; M. Stephanos; R. Mithany; M. Abdelkarim; G. Venkatesan; A. Aqsalan ; J. Taylor; M. Fok; A. Kattakayam; K. Rajput ; K. Bevan; H.-K. Kim; L. Salih; R. Sabaratnamznab287_Supplementary_DataClick here for additional data file."} +{"text": "Fusarium disease of oats reduces yield quality due to decreasing germination that is caused by the contamination of grain with mycotoxins produced by Fusarium fungi. The aim of this study was to characterize the resistance of naked breeding lines of oats to fungal grain infection and to contamination with T-2 and HT-2 toxins. Thirteen naked oat breeding lines and two naked varieties, Nemchinovsky 61 and Vyatskiy, as well as a husked variety Yakov, were grown under natural conditions in the Nemchinovka Federal Research Center in 2019\u20132020. The contamination of grain with fungi was determined by the mycological method and real-time PCR. The analysis of mycotoxins was carried out by ELISA. In oats, Alternaria (the grain infection was 15\u201390 %), Cochliobolus (1\u201333 %), Cladosporium (1\u201319 %), Epicoccum (0\u201311 %), and Fusarium (3\u201317 %) fungi prevailed in the grain mycobiota. The predominant Fusarium species were F. poae (its proportion among Fusarium fungi was 49\u201368 %) and F. langsethiae (29\u201328 %). The highest amounts of F. langsethiae DNA ((27.9\u201371.9) \u00d7 10\u20134 pg/ng) and T-2/HT-2 toxins (790\u20131230 \u03bcg/kg) were found in the grain of husked oat Yakov. Among the analysed naked oat lines, the amount of F. langsethiae DNA varied in the range of (1.2\u201342.7) \u00d7 10\u20134 pg/ng,and the content of T-2/HT-2 toxins was in the range of 5\u2013229 \u03bcg/kg. Two oat breeding lines, 54h2476 and 66h2618, aswell as a new variety, Azil (57h2396), can be characterized as highly resistant to infection with Fusarium fungi and contaminationwith mycotoxins compared to the control variety Vyatskiy. Over the past decade, the amount of information on Fusariumdisease of oats (Avena sativa L.) has increased dramatically.The infection of oats caused by different Fusarium Link speciesis recognized as one of the most devastating diseasesof this cereal crop. In addition to direct negative impacts oneconomically valuable traits, such as the loss of grain yield, the harmfulness of Fusarium fungiis determined by their ability to produce different mycotoxinsthat accumulate in infected grains. Mycotoxins produced bymany Fusarium species remain in processed products and,when consumed by people or animals, can cause immunosuppressionand various health issues .Current studies of the Fusarium problem in oats concern theanalysis of grain infection by different fungal species and thedetermination of mycotoxin contents in grain , the study of host-pathogen interactions and the search for potential sourcesof resistance to the disease, including the use of molecularanalysis methods .The composition and representation of Fusarium speciescausing the disease in oats vary significantly and depend onthe place of cultivation and the prevailing weather conditionsduring the growing season . As a rule,the main species of Fusarium fungi responsible for disease inoats are F. poae (Peck) Wollenw., F. sporotrichioides Sherb.and F. langsethiae Torp & Nirenberg , while F. graminearum Schwabe and F. avenaceum (Fr.) Sacc. occur less often. All of the mentioned Fusarium fungiare capable of producing various mycotoxins. The results ofnumerous studies demonstrate a high contamination of grainwith T-2 and HT-2 toxins produced by F. sporotrichioidesand F. langsethiae .In the breeding of oat varieties, the trait of resistance toFusarium disease was not taken into account for a long timedespite the problem with grain infection of this cereal crop.The main challenge of the evaluation of resistance of oatgenotypes to the disease in the field is the absence or weaksymptoms of Fusarium infection on oat panicles, in contrastto the noticeable specific symptoms on heads of other smallgraincereals . However, Fusariumfungi and mycotoxins in the grain of asymptomatic spikeletsin panicles are often detected, and oat genotypes can be significantlydifferent according to their amounts. In addition, itis already well known that the disease severity is determinedby factors such as the weather and infection pressure.There are no cereals that are immune to infection withFusarium fungi; however, different degrees of resistance areobserved among genotypes. Previously, it was mentioned thata wheat genotype resistant to infection with one Fusariumspecies also tends to be resistant to other species of this genus. Additionally, several types of resistanceto Fusarium disease in cereals have been described andcommonly divided into at least five separate types : resistance against initial infection(type I), resistance against the spread of infection (II),resistance against grain infections (III), tolerance (IV), andresistance to mycotoxin accumulation or degradation (V). Inthe sowing oats (A. sativa L.), two subspecies, husked oats(A. sativa subsp. sativa L.) and naked oats (A. sativa subsp. nudisativa(Husn.) Rod. et Sold.), which differ from each otherin their morphological characteristics, biochemical propertiesand resistance to abiotic and biotic factors, were described. Therelatively high resistance of naked oats to Fusarium infectionof grain, in comparison with husked oats, has been repeatedlynoted .Earlier, information on the resistance of oat genotypes fromthe VIR collection to Fusarium disease, which was analysedunder conditions of artificial inoculation with F. sporotrichioides,was systematized in the Catalogue . A successful example of combining the efforts ofdifferent research groups was the breeding of a new varietyof naked oats, Vsadnik, which is the first officially registeredvariety in Russia characterized as relatively resistant to Fusariumdisease. This variety accumulated significantly loweramounts of mycotoxins in the grain than the standard huskedvariety Konkur, which is cultivated over a wide area in Russia.https://gossortrf.ru/gosreestr// )Since 2010, 11 new varieties of naked oats have been includedin the State Register.At present, the attention of many Russian oat breeders isfocused on the creation of naked oat varieties characterizedby improved grain quality and resistance to fungal diseases. The progress achievedin the breeding process is evidenced by the increase in thenumber of naked oat varieties included in the \u201cState Registerof Selection Achievements\u2026\u201d, which in 2020 consisted of 121 varieties of husked oats and 15 varieties of naked oats1. The aim of this study was to characterize the resistance ofnaked oat lines to contamination of grain with Fusarium fungiand T-2/HT-2 toxins. These oat genotypes are the breedingmaterial of the Federal Research Center \u201cNemchinovka\u201d andwere cultivated in field experiments under natural conditions.Oats breeding material. 10 and 13 naked oat breeding lines(A. sativa subsp. nudisativa (Husn.) Rod. et Sold.) were analysedin 2019 and 2020, respectively. In addition, the nakedoat varieties Nemchinovsky 61 (NFRC) and Vyatsky as acontrol and the standard husked variety Yakov (NFRC)were included in the study (Table 1).Cultivation of breeding material. In 2019\u20122020, theanalysed varieties and breeding lines of oats were grown afterspring barley as the previous crop in the experimental 10 m2plots in the nursery of the NFRC according to the state varietytesting methodology2. The harvesting of oats was carriedout at the full-mature stage: August 8, 2019, and August 16,2020. The weather conditions in the growing seasons of 2019and 2020 were different (Table 2). The summer period of2020 was characterized by an increased temperature in June-August compared to the long-term average values, as well asa 1.7\u20122.6 times excess of the total precipitation in May-Julycompared to this period in 2019.Mycological analysis of grain infection. To evaluate thefungal infection and species composition of oat grain mycobiota,100 seeds of each genotype were surface sterilized in5 % sodium hypochlorite and washed with sterilized water.Then, grains were placed on potato sucrose agar medium(PSA) in Petri dishes , and incubated in thedark at 24 \u00b0\u0421 in an MIR-254 thermostat . Afterseven days, the number and species diversity of fungi isolatedfrom the grain were registered.The taxonomic status of the isolated fungi was determinedby the sum of macro- and micromorphological charactersaccording to the manuals .The grain infection by definite fungi was quantified as thepercentage ratio of the number of grains from which thesefungi were isolated to the total number of analysed grains.Analysis of F. langsethiae DNA content. Ten grams ofgrain of every oat genotype was homogenized separatelyusing sterilized grinding chambers of a Tube Mill Controlbatch mill at 25,000 rpm for 30\u201345 s. TotalDNA from 200 mg of grain flour was isolated using the CTAB method . Genomic DNA was isolatedfrom the mycelium of a typical F. langsethiae strain from thecollection of the Laboratory of Mycology and Phytopathologyof All-Russian Institute of Plant Protection using a GenomicDNA Purification Kit according to the manufacturer\u2019s protocol.The DNA concentrations from the grain samples and fromfungal strains were determined using a Qubit 2.0 fluorometerwith a Quant-iT dsDNA HS Assay Kit . Before the start of quantitative PCR (qPCR),the concentrations of all DNA samples were aligned to20\u201260 ng/ \u03bcL.The F. langsethiae DNA content in every DNA sample extractedfrom oat flour was estimated by qPCR with a TaqManprobe fluorescently labelled with Cy5 dye and a BHQ-2quencher .Amplification reactions were run using the CFX 96 Real-Time System according to the followingprotocol: 1 \u00d7 ; 40 \u00d7 . The DNA content was calculated as the ratio offungal DNA to total DNA in each sample (pg/ng).Analysis of mycotoxin content. The mycotoxins were extractedfrom 1 g of oat flour with 5 mL of an acetonitrile:watermixture for 14\u201316 h. The total amounts of T-2 andHT-2 toxins in the extracts were determined using an indirectcompetitive enzyme-linked immunosorbent assay. The diagnosticcertified test system \u201cT-2 toxin\u2013ELISA\u201d was used. The limit of mycotoxin detectionwas 4 \u03bcg/kg.Statistical analysis. The contents of fungal DNA and mycotoxinsin the grain of each genotype were analysed at leasttwice. The mean values, confidence intervals, Pearson coefficientsof correlation (r) between quantitative parameters andvariance analysis (ANOVA) were performed using MicrosoftExcel 2010, Minitab 17 and Statistica 10.0 programs. Differenceswere considered significant at p < 0.05.Fungal infection of oat grainThe predominance of fungi belonging to Alternaria Nees, CochliobolusDrechsler, Cladosporium Link, Epicoccum Link,and Fusarium genera in the grain of the analysed oat genotypeswas revealed by the mycological method. In addition, the fungiAcremonium Link, Arthrinium Kunze, Gliocladium Corda,Microdochium Syd. & P. Syd., Mucor Fresen., NigrosporaZimm., Penicillium Link, Phoma Sacc., and TrichotheciumLink genera were sporadically isolated from the grain.Alternaria fungi were the most abundant in the oat grainmycobiota in both years of the study . The majorityof isolated Alternaria spp. was represented by fungi belongingto section Alternaria (86 % in 2019 and 84 % in 2020),and the remaining isolates were identified as Alternaria fungibelonging to section InfectoriaeGrain infection with Cochliobolus fungi, including Bipolarissorokiniana Shoemaker, Drechslera avenae (Eidam) Sharif (Pyrenophora avenae Ito & Kurib) and others, differedsignificantly in the years of study ( p = 0.000012). In 2019, oatgrain infection with Cochliobolus spp. varied in the range of1\u201313 %, whereas in 2020, its incidence was 6\u201333 %.The proportion of grains colonized by Fusarium spp. didnot differ significantly between the years of study. The incidencesof Fusarium infection of grain of naked oat lines andthe variety Nemchinovsky 61 varied from 5 to 17 % in 2019and from 3 to 13 % in 2020. For the husked variety Yakov, theincidences of Fusarium grain infection were 26 and 17 % in2019 and 2020, respectively. For the control variety Vyatsky,the incidences were 5 and 3 %, respectively. In both years ofthe study, only two lines, 54h2476 and 66h2618, were characterizedby lower grain infection or coincidence with thecontrol variety Vyatsky grain infection with Fusarium spp. Atleast nine Fusarium species were identified in the mycobiotaof oat grains, but toxin-producing F. poae and F. langsethiaespecies prevailed in both years. The proportions of these fungiamong Fusarium spp. isolates were 49\u201268 % for F. poae and29\u201228 % for F. langsethiae.Contents of F. langsethiae DNA and \u0422-2/\u041d\u0422-2 toxinsThe highest content of F. langsethiae DNA was revealedin the grain of the husked variety Yakov and amounted to71.9 \u00d7 10\u20134 pg/ng in 2019 and 27.9 \u00d7 10\u20134 pg/ng in 2020. Inthe grain of the control naked variety Vyatsky, the F. langsethiaeDNA content was significantly lower, reaching11.0 \u00d7 10\u20134 pg/ ng in 2019 and 1.2 \u00d7 10\u20134 pg/ng in 2020. In2019, only three oat breeding lines, 2h2532, 52h2467, and50h2613, contained more F. langsethiae DNA than the controlvariety Vyatsky. In 2020, the contents of fungal DNA in thegrain of all analysed oat breeding lines were higher than thatin the control variety .The mycological analysis revealed the presence of fungal infectionin the grain of all oat genotypes; however, the numberand species composition of identified micromycetes varieddepending on oat genotype and crop year.The average temperatures during the vegetation seasons inboth years were similar; however, the precipitation in May-August in 2020 was two times higher than that observed inthe previous year. As a result, the average grain infection withCochliobolus increased fourfold in 2020; at the same time,grain infections with Alternaria, Cladosporium and Fusariumfungi significantly decreased 1.4\u20123.5 fold.With the high incidence of Cochliobolus infection of oatgrain in 2020, a significant negative correlation between infectionwith Cochliobolus and Alternaria fungi was revealed. Previously, antagonistic relationshipsbetween these two groups of fungi associated with small-graincereals were also established . Perhaps the Cochliobolus were morecompetitive in the wetter conditions, and these fungi had anadvantage over Alternaria and Fusarium fungi.Significant positive correlations between grain infectionand Alternaria and Fusarium fungi andEpicoccum and Fusarium fungi wererevealed in 2019. A symbiotic relationship between Alternariaand Fusarium fungi in cereal grain has been established repeatedly.Among all Fusarium fungi isolated from oat grains, theF. poae and F. langsethiae strains were dominant. F. poae producenivalenol and diacetoxyscirpenol and F. langsethiaeis astrong producer of T-2/HT-2 toxins and DAS. In Russia, theamounts of T-2/HT-2 toxins are regulated in oat grains for foodand feed, and the maximal permissible limit is 100 \u03bcg/kg3, 4.The relatively low infection of grain with F. langsethiaeled to high amounts of detected mycotoxins. Therefore, weevaluated the breeding material by both the presence ofF. langsethiae DNA and the accumulation of the sum of T-2and HT-2 toxins in grain.The highest incidence of infection with F. langsethiae andthe maximal amounts of fungal DNA and T-2/HT-2 toxins werefound in the grain of the husked variety Yakov. In comparisonwith this genotype, all naked breeding lines and varieties were less infected and contained significantly less fungal DNA andmycotoxins. Significant positive correlations between theamounts of F. langsethiae DNA and T-2/HT-2 toxins in thegrain of naked oat genotypes were found .The results of our study demonstrated significant differencesin oat breeding lines and varieties according to the contentof F. langsethiae DNA in grain, although all genotypes werecontaminated with T-2/HT-2 toxins. Thus, it is worth emphasizingagain that the evaluation of oat resistance to Fusariumdisease should be carried out according to several parameters.It has been suggested that oat resistance type V to Fusariumdisease depends on the mycotoxin type and that the QTLs associatedwith a low level of accumulation of deoxynivalenolin grain might not provide the resistance of the same genotypeto other mycotoxins .However, comparison of the results obtained in our study and later studies of the same oat genotypesunder different conditions, genotype VIR-7766 , varieties Argamak and Vyatsky , demonstrated a relativelyhigh resistance of these oats to the accumulation of differentmycotoxins, such as T-2/HT-2 toxins and deoxynivalenol.The genetic basis of oat breeding lines plays a key role intheir resistance to Fusarium disease. In the pedigree of twonaked oat lines, characterized by high contents of fungal DNAand mycotoxins in 2019, the Zalp variety was recorded. Apparently,the crossing of breeding material with this varietycan promote an increase in genotype susceptibility to Fusariumdisease.The breeding lines of naked oats created in the Federal ResearchCenter \u201cNemchinovka\u201d were evaluated by the sum ofparameters characterized by different types of oat resistanceto Fusarium disease. The amounts of F. langsethiae DNA andT-2/HT-2 toxins produced by this fungus were analysed, andbased on the results obtained during a two-year study, undergrowth conditions, two lines of naked oats, 54h2476 and66h2618, and the new variety, Azil (Line 57h2396 in 2019),demonstrated relatively high resistance to F. langsethiae infectionand mycotoxin contamination compared with the controlnaked variety Vyatsky. These lines should be actively used tocreate new varieties that do not accumulate mycotoxins andare characterized by high-quality grain.The authors declare no conflict of interest.Batalova G.A., Loskutov I.G., Shevchenko S.N., Zhuikova O.A.,Krotova N.V., Tulyakova M.V. On breeding of naked oat cultivarvirovets. Russ. Agric. Sci. 2019;45(5):412-415. DOI 10.3103/S1068367419050033.Bj\u00f8rnstad \u00c5., He X., Tekle S., Klos K., Huang H.F., Tinker N.A.,HelgeD. Genetic variation and associations involving Fusariumhead blight and deoxynivalenol accumulation in cultivated oat(Avena sativa L.). Plant Breed. 2017;136:1-17. DOI 10.1111/pbr.12502.Boutigny A.-L., Richard-Forget F., Barreau C. Natural mechanismsfor cereal resistance to the accumulation of Fusarium trichothecenes Eur. J. Plant Pathol. 2008;121:411-423. DOI 10.1007/s10658-007-9266-x.Burkin A.A., Kononenko G.P., Gavrilova O.P., Gagkaeva T.Yu. Mycotoxicologicalexamination of oat grain and products of its processing.In: Current Mycology in Russia. Vol. 5. Proc. III Int. Mycol.Forum, 14\u201215 Apr. 2015. Moscow, 2015;221-223. (in Russian)Chrpov\u00e1 J., Palicov\u00e1 J., \u0160t\u011brbov\u00e1 L., Tr\u00e1vn\u00ed\u010dkov\u00e1 M., Dumalasov\u00e1 V.,Chourov\u00e1 M. Resistance against Fusarium head blight in oats.Zemdirbyste-Agriculture. 2020;107(1):49-54. DOI 10.13080/z-a.2020.107.007.De Colli L., De Ruyck K., Abdallah M.F., Finnan J., Mullins E., KildeaS., Spink J., Elliott C., Danaher M. Natural co-occurrence ofmultiple mycotoxins in unprocessed oats grown in Ireland withvarious production systems. Toxins. 2021;13(3):188. DOI 10.3390/toxins13030188.Divon H.H., Razzaghian J., Udnes-Aamot H., Klemsdal S.S. Fusariumlangsethiae (Torp and Nirenberg), investigation of alternativeinfection routes in oat. Eur. J. Plant Pathol. 2012;132:147-161.DOI 10.1007/s10658-011-9858-3.Ellis M.B. Dematiaceous Hyphomycetes. Kew, 1971.Foroud N.A., Baines D., Gagkaeva T.Yu., Thakor N., Badea A.,Steiner B., B\u00fcrstmayr M., B\u00fcrstmayr H. Trichothecenes in cerealgrains \u2013 an update. Toxins. 2019;11(11):634. DOI 10.3390/toxins11110634.Fredlund E., Gidlund A., Sulyok M., B\u00f6rjesson T., Krska R., OlsenM., Lindblad M. Deoxynivalenol and other selected Fusariumtoxins in Swedish oats \u2013 occurrence and correlation to specificFusariumspecies. Int. J. Food Microbiol. 2013;167(2):276-283.DOI 10.1016/j.ijfoodmicro.2013.06.026.Gagkaeva T.Yu., Gavrilova O.P., Loskutov I.G., Blinova E.V., AnikinaL.V. Evaluation of oat accessions from the VIR collection forFusarium head blight resistance. In: Catalogue of World VIR Collection.Vol. 808. St. Petersburg, 2012. (in Russian)Gagkaeva T.Yu., Gavrilova O.P., Orina A.S., Blinova E.V., LoskutovI.G. Response of wild Avena species to fungal infection ofgrain. Crop J. 2017;5(6):499-508. DOI 10.1016/j.cj.2017.04.005.Gagkaeva T.Yu., Gavrilova O.P., Yli-Mattila T., Loskutov I.G. Thesources of resistance to Fusarium head blight in VIR oat collection.Euphytica. 2013;191(3):355-364. DOI 10.1007/s10681-013-0865-7.Gannibal Ph.B. Factors affecting Alternaria appearance in grains inEuropean Russia. Agricultural Biology (Sel\u2019skokhozyaistvennayaBiologia). 2018;53(3):605-615. DOI 10.15389/agrobiology.2018.3.605eng.Gavrilova O.P., Gannibal Ph.B., Gagkaeva T.Yu. Fusarium and Alternariafungi in grain of oats grown in the North-Western Russiaregarding cultivar specificity. Agricultural Biology (Sel\u2019skokhozyaistvennayaBiologia). 2016;51(1):111-118. DOI 10.15389/agrobiology.2016.1.111eng.Gerlach W., Nirenberg H.I. The Genus Fusarium \u2013 a Pictorial Atlas.Berlin, 1982.Hautsalo J., Jauhiainen L., Hannukkala A., Manninen O., Vetel\u00e4inenM., Pietil\u00e4 L., Peltoniemi K., Jalli M. Resistance to Fusariumhead blight in oats based on analyses of multiple field and greenhousestudies. Eur. J. Plant Pathol. 2020;158:15-33. DOI 10.1007/s10658-020-02039-0.Hautsalo J., Latvala S., Manninen O., Haapalainen M., HannukkalaA., Jalli M. Two oat genotypes with different field resistance toFusarium head blight respond similarly to the infection at spikeletlevel. J. Plant Pathol. 2021;103:299-304. DOI 10.1007/s42161-020-00670-8.He X., Skinnes H., Oliver R.E., Jackson E.W., Bj\u00f8rnstad \u00c5. Linkagemapping and identification of QTL affecting deoxynivalenol(DON) content (Fusarium resistance) in oats (Avena sativa L.).Theor. Appl. Genet. 2013;126:2655-2670. DOI 10.1007/s00122-013-2163-0.Hofgaard I.S., Aamot H.U., Torp T., Jestoi M., Lattanzio V.M.T.,KlemsdalS.S., Waalwijk C., Van der Lee T., Brodal G. Associationsbetween Fusarium species and mycotoxins in oat and springwheat from farmers\u2019 fields in Norway over a six-year period. WorldMycotoxin J. 2016;9:365-378. 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Alternaria and Fusariumin Norwegian grains of reduced quality \u2012 a matched pair samplestudy. Int. J. Food Microbiol. 2004;93(1):51-62. DOI 10.1016/j.ijfoodmicro.2003.10.006.Kurowski T.P., Wysocka U. Fungal communities colonizing grain ofhulled and naked oat grown under organic farming system. Phytopathologia.2009;54:53-59.Loskutov I.G., Blinova E.V., Gavrilova O.P., Gagkaeva T.Yu. Thevaluable characteristics of oats genotypes and resistance to Fusariumdisease. Vavilovskii Zhurnal Genetiki i Selektsii = VavilovJournal of Genetics and Breeding. 2016;20(3):286-294. DOI10.18699/VJ16.151. (in Russian)Loskutov I.G., Shelenga T.V., Konarev A.V., Vargach Yu.I., PorokhovinovaE.A., Blinova E.V., Gnutikov A.A., Rodionov A.V. Modernapproach of structuring the variety diversity of the naked and coveredforms of cultural oats (Avena sativa L.). Ecol. Genet. 2020;18(1): 27-41. 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Development of Fusarium langsethiaein commercial cereal production. Eur. J. Plant Pathol.2013;136:159-170. DOI 10.1007/s10658-012-0151-x.Orina A.S., Gavrilova O.P., Gagkaeva T.Yu. Adaptation of the quantitativePCR method for the detection of the main representativesof cereal grain mycobiota. MIR J. 2018;5(1):78-83. DOI10.18527/2500-2236-2018-5-1-78-83.Orina A.S., Gavrilova O.P., Gagkaeva T.Yu., Gannibal Ph.B. MicromycetesAlternaria spp. and Bipolaris sorokiniana and mycotoxinsin the grain from the Ural region. Mikologiya i Fitopatologiya= Mycology and Phytopathology. 2020;54(5):365-377. DOI10.31857/S0026364820050086. (in Russian)Orina A.S., Gavrilova O.P., Gagkaeva T.Yu., Loskutov I.G. Symbioticrelationships between aggressive Fusarium and Alternariafungi colonizing oat grain. Agricultural Biology (Sel\u2019skokhozyaistvennayaBiologiya). 2017;52(5):986-994. DOI 10.15389/agrobiology. 2017.5.986eng.Samson R.A., Hoekstra E.S., Frisvad J.C., Filtenborg O. Introductionto Food- and Airborne Fungi. Utrecht, 2002.Sch\u00f6neberg T., Jenny E., Wettstein F.E., Bucheli T.D., Mascher F.,Bertossa M., Musa T., Seifert K., Gr\u00e4fenhan T., Keller B., VogelgsangS. Occurrence of Fusarium species and mycotoxins in Swissoats \u2012 impact of cropping factors. Eur. J. Agron. 2018;92:123-132.DOI 10.1016/j.eja.2017.09.004.Tekauz A.B., Mitchell Fetch J.W., Rossnagel B.G., Savard M.E. Progressin assessing the impacy of Fusarium head blight on oat inwesternCanada and screening of avena germplasm for resistance.Cereal Res. Commun. 2008;36(8):49-56. DOI 10.1556/CRC.36.2008.Suppl.B.8.Tekle S., Dill-Macky R., Skinnes H., Tronsmo A.M., Bj\u00f8rnstad \u00c5.Infection process of Fusarium graminearum in oats (Avena sativaL.). Eur. J. Plant Pathol. 2012;132:431-442. DOI 10.1007/s10658-011-9888-x.Tekle S., Lillemo M., Skinnes H., Reitan L., Buraas T., Bj\u00f8rnstad \u00c5.Screening of oat accessions for Fusarium head blight resistanceusingspawn-inoculated field experiments. Crop Sci. 2018;58:143-151. DOI 10.2135/cropsci2017.04.0264.Torp M., Nirenberg H.I. Fusarium langsethiae sp. nov. on cereals inEurope. Int. J. Food Microbiol. 2004;95:247-256. DOI 10.1016/j.ijfoodmicro.2003.12.014.Vargach Yu.I., Golovin S.E., Loskutov I.G. Research on micromycetesin oats (Avena sativa L.) under the conditions of Stupino district,Moscow province. Trudy po Prikladnoy Botanike, Genetike iSelektsii = Proceedings on Applied Botany, Genetics and Breeding.2019;180(3):96-105. DOI 10.30901/2227-8834-2019-3-96-105. (in Russian)Willforss J., Leonova S., Tillander J., Andreasson E., Marttila S., OlssonO., Chawade A., Levander F. Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with differentresistance. J. Proteomics. 2020;218:103688. DOI 10.1016/j.jprot.2020.103688Yan W., Fregeau-Reid J., Rioux S., Pageau D., Xue A., Martin R.,Fedak G., de Haan B., Lajeunesse J., Savard M. Response of oatgenotypes to Fusarium head blight in Eastern Canada. Crop Sci.2010;50:134-142. DOI 10.2135/cropsci2009.03.0129Yli-Mattila T., Paavanen-Huhtala S., Jestoi M., Parikka P., HietaniemiV., Gagkaeva T., Sarlin T., Haikara A., Laaksonen S., Rizzo A.Real-time PCR detection and quantification of Fusarium poae,F. graminearum, F. sporotrichioides and F. langsethiae in cereal grains in Finland and Russia. Arch. Phytopathol. Plant Protect.2008;41(4):243-260. DOI 10.1080/03235400600680659.Zhuikova O.A., Batalova G.A. Analysis of the main diseases of hulledoat varieties in the nursery for competitive trials of the FederalAgrarian Center of the Northeast. In: Int. Conf. \u201cMethods andTechnologies in Plant Breeding and Crop Industry\u201d. Apr. 1\u20125,2019. Kirov, Russia. Kirov, 2019;21-24. (in Russian)Zhuikova O.A., Gradoboeva T.P., Batalova G.A. Effectiveness ofinfectious backgrounds in evaluating oat for resistance to fungaldiseases. Rossiiskaya Sel\u2019 skokhozyaistvennaya Nauka = RussianAgricultural Sciences. 2020;(3):10-13. DOI 10.31857/S2500262720030035. (in Russian)"} +{"text": "Nebularmis, a recently erected genus within the Echiniscus lineage. Nebularmis auratussp. nov. and Nebularmis burmensissp. nov. are described from the Eastern Yoma Mountains and the Shan Hills (Myanmar), Nebularmis bhutanensissp. nov. is described from the Eastern Himalayas (Bhutan), and Nebularmis indicussp. nov. is described from the foothills of the Western Ghats . Moreover, males are reported in populations of the last two species.\u00a0All known members of the genus can be phenotypically differentiated based on minute details of their dorsal sculpture and claws. Moreover, a very wide tropical distribution is demonstrated for Nebularmis cirinoi, recorded for the first time from islands of the Malay Archipelago. Furthemore, novel morphological, genetic, and geographic data allowed for the clarification of the generic diagnosis. Currently available data favor a scenario under which Nebularmis evolved in Southeast Asia and later dispersed to other regions of the globe.Recent years have brought undeniable progress in tardigrade taxonomy, and speciose complexes were detected in a number of phylogenetic lineages. The family Echiniscidae is one such lineage; it is one of the most diverse groups of limno-terrestrial tardigrades and can be characterized as having achieved great evolutionary success. In this contribution, using populations representing several species that originated from the Indomalayan region, we reconstructed phylogenetic affinities within The online version contains supplementary material available at 10.1186/s40851-021-00172-0. Echiniscoides and Batillipes [Pseudechiniscus and Hypechiniscus [Milnesium was recently demonstrated to be rich in species [Macrobiotus, Ramazzottius, Richtersius, Paramacrobiotus and Platicrista [Hypsibius exemplaris as a new model metazoan species [The diversity of tardigrades has been intensively studied in recent years using modern species delimitation tools, including statistical morphometry and molecular analyses. Consequently, numerous new species have been detected in every major lineage of the phylum, and many are currently awaiting formal descriptions. Among marine heterotardigrades, examples include tillipes , 2, terrhiniscus , 4, in t species , and exaticrista \u201311. Resoticrista by narroticrista , 14, but species that is species , 17). As species \u201322.Echiniscus competes with Macrobiotus for the position of the most speciose tardigrade genus [Echiniscus lineage [Echiniscus [Nebularmis, was created for the widespread Palearctic species Nebularmis reticulatus [Nebularmis has large red eyes and a highly altered ventral cuticular system, with uniform wrinkling in the central part of the venter and characteristic, clearly delineated, thick and densely granulated subcephalic and genital plates. Such a combination of traits makes Nebularmis easy to recognize; nevertheless, the state of taxonomy within the genus leaves much to be desired. Almost all known Nebularmis species are dubious, most likely synonymous with N. reticulatus [Nebularmis phocae [Comprising more than a hundred species, de genus . High ta lineage ; recentlhiniscus , 26. Oneiculatus , 28 and s phocae , cannot s phocae , posing s phocae .Nebularmis in a new light. Four new species are described from regions that were not previously subjected to tardigrade sampling [Nebularmis based on new morphological data, present hypotheses on its evolution, and finally discuss our findings in the context of phylogeny of echiniscids, one of the stunningly morphologically complex tardigrade groups [th International Symposium on Tardigrada, as has been successfully undertaken for another meiofaunal phylum, Rotifera [With the opportunity to analyse many Indomalayan populations representing this uncommon genus, we aim to present the intrageneric diversity and phylogeography of sampling , illustrsampling . We amene groups . Last, wRotifera , to offiNebularmis were extracted from 11 moss and lichen samples collected in South and Southeast Asia , Llanganuco Valley , Doi Inthanon , and Greenland , Mount Aspiring National Park, the South Island of New Zealand; leg. D.S. Horning, October 1970; NZ-525; 1 individual; Canaan Road, Abel Tasman National Park, the South Island of New Zealand; leg. D.S. Horning, April 1971).Individuals belonging to the rare genus eenland , 0077 (N. bhutanensissp. nov.), 0078 (N. burmensissp. nov.), and 0079 (N. indicussp. nov.). DNA sequences were deposited in GenBank.Specimens subjected to light microscopy and morphometry analyses were mounted in a small drop of Hoyer\u2019s medium and examined under an Olympus BX 51 PCM and NCM paired with an Olympus DP74 digital camera. Specimens for SEM imaging were COar plate . Morphomregister . Raw morEchiniscus testudo [Diploechiniscus oihonnae [DNA was extracted from individual animals following a Chelex\u00ae 100 resin (Bio-Rad) extraction method , 41. Vou testudo and Diploihonnae as outgroihonnae , 46. Theoihonnae , with gaoihonnae in BioEdoihonnae . Alignmehttps://tree.bio.ed.ac.uk/software/figtree.The sequences for the nuclear gene fragments were concatenated to generate a 2803-bp matrix in SequenceMatrix ; see Sup. Using PNebularmis species distributions were coded as broad but regionalized . The maximum number of areas at a node was set to 3.Consensus trees constructed from datasets a and c\u2013d shared identical topologies, whereas the tree based on dataset b was divergent from the remaining phylogenies. Consequently the first 9000 trees were removed from the set of trees a and b, and the remaining 1000 trees were used in independent statistical dispersal-vicariance analyses (S-DIVA) , 58, impPhylum: Tardigrada Doy\u00e8re, 1840 .Class: Heterotardigrada Marcus, 1927 .Order: Echiniscoidea Richters, 1926 .Family: Echiniscidae Thulin, 1928 .Nebularmis G\u0105siorek & Michalczyk, 2020 in G\u0105siorek et al. [Genus: k et al. striae. Additionally, occasional sparse intracuticular pillars and/or micropores may be visible in some portions of the dorsal plates, especially in the scapular plate. Ventral plates present, developed as subcephalic and genital plates. Ventral cuticle wrinkled. Long, sabre-like claws. Larvae and juveniles with minute sparse pores and densely arranged intracuticular pillars in the dorsal plates.Amended diagnosis: Small- to medium-sized echiniscids with red granulate eyes. Long, rigid and thick buccal tube lacking stylet supports. Cirrophores of the cephalic cirri weakly outlined. Only cephalic cirri present. Two pairs of segmental plates and three median plates. Incisions (notches) on caudal plate. Pseudosegmental plates absent. Dorsal plate sculpture composed of an intracuticular sponge layer and large epicuticular, round or slightly hexagonal flat granules that may be connected by Figures Description. Females : Body dark orange to red and stout : Without a gonopore and with a poreless scapular plate. Otherwise, same as adult females.Larvae and eggs: Not found.Type material: Holotype and 4 paratypes . All slides deposited in UJ.Type locality: 17\u00b028\u203255\u2033N, 97\u00b005\u203253\u2033E, 1073\u2009m asl; Myanmar, Mon, Eastern Yoma Mountains, Kyaiktiyo; moss from tree bark, mountain deciduous forest. This is the first record of tardigrades from Myanmar.auratus\u2009=\u2009golden. The name refers to locus typicus, as Golden Rock is a typical Buddhist pilgrim destination in Myanmar. An adjective in the nominative singular.Etymology: From Latin Nebularmis lineage in three of the performed analyses to 17.0% .Phylogenetic position. The species was inferred as the basal tus Fig.\u00a0b. Both tFigures 4Description. Females : Body dark orangish-red and stout, with large dark red eyes not visible after mounting in Hoyer\u2019s medium. Large, swollen cephalic papillae (secondary clavae) and bluntly terminated (primary) clavae. Peribuccal cirri with short cirrophores. Cirrus A short, with evident cirrophore and slightly thicker flagellum at its proximal end.striae of various thicknesses : Qualitatively similar to females. Body ovoid Fig.\u00a0. CephaliJuveniles, larvae and eggs: Not found.Type material: Holotype , allotype and one paratype . Holotype and allotype deposited in UJ, paratype deposited in UP.Type locality: 37\u00b029\u203232\u2033N, 89\u00b021\u203249\u2033E, 3120\u2009m asl; Bhutan, Eastern Himalayas, Paro Taktsang; moss from rock, pine forest. The first record of tardigrades from Bhutan.bhutanensis\u2009=\u2009inhabiting Bhutan. The name underlines terra typica. An adjective in the nominative singular.Etymology: From Latin Phylogenetic position. Unknown. The species has the most distinctive sculpture subtype within the entire genus; thus, acquiring DNA sequences is important from a phylogenetic perspective.Figures Description. Females : Body dark orange and stout . One qualitative difference with respect to adults is the lack of gonopore.Juveniles : Body 139\u2009\u03bcm long (scapular plate length 39.5\u2009\u03bcm). Cephalic appendage lengths: cirrus internus 10.0\u2009\u03bcm, cephalic papilla 4.6\u2009\u03bcm, cirrus externus 11.6\u2009\u03bcm, (primary) clava 5.0\u2009\u03bcm, cirrus A 18.9\u2009\u03bcm. Body appendage lengths: spine I 1.7\u2009\u03bcm, papilla IV 2.6\u2009\u03bcm. Five teeth on the collar. Claw branch heights: 7.5\u20138.7\u2009\u03bcm (spurs 1.4\u20131.9\u2009\u03bcm). Gonopore and anus absent.Larvae : Body 120\u2009\u03bcm long (scapular plate length 28.1\u2009\u03bcm). Cephalic appendage lengths: Eggs: Not found.Type material: Holotype and 8 paratypes . Slides MM.010.08\u201314 deposited in UJ, MM.010.15\u201316 deposited in UP.Type locality: 20\u00b038\u203228\u2033N, 97\u00b004\u203214\u2033E, 1333\u2009m asl; Myanmar, Shan, Shan Hills, Taunggyi, Kakku Pagodas; moss and lichen from tree bark, rural habitat. The first record of tardigrades from Myanmar.burmensis\u2009=\u2009inhabiting Burma . The name underlines terra typica. An adjective in the nominative singular.Etymology: From Latin Nebularmis indicussp. nov. to 14.8% .Phylogenetic position. The species was inferred to be a sister species to ov. Fig.\u00a0. The p-dFigures\u00a0Description of Indomalayan populations. Females : Body orange and stout : Qualitatively similar to females. Epicuticular granules, with the exception of the central portions of median plates m1\u20132, completely merged, giving the dorsal plate surface a smooth appearance Fig. b. GonopoLarvae and eggs: Not found.Material examined: Celebes: 12 \u2640\u2640, 4 juveniles , Tidore: 2\u2640\u2640 . All slides deposited in UJ.Nebularmis burmensissp. nov. + Nebularmis indicussp. nov. clade : Body dark red and stout : Body small and less plump than that of female Fig.\u00a0. Dorsal Juveniles : Gonopore absent; the remaining traits identical to adults.Larvae : Median plate m3 undeveloped. Dorsal sculpturing disparate from older life stages; belts of endocuticular pillars arranged in an ornamented pattern, especially in the central portions of plates Fig.\u00a0. EpicutiEggs: Up to four dark orange eggs in an exuvia.Type material: Holotype , allotype and 4 paratypes . Hologenophores: two specimens of unidentified sex , one exuvia containing eggs (IN.075.02). Slides IN.040.02\u201303 deposited in UP, and the remaining slides deposited in UJ.Type locality: 15\u00b005\u203244\u2033N, 74\u00b012\u203241\u2033E, 77\u2009m asl; India, Goa, Western Ghats, Netravali; moss from tree bark, spice plantation.Additional locality: 14\u00b058\u203201\u2033N, 74\u00b009\u203230\u2033E, 100\u2009m asl; India, Goa, Western Ghats, Cotigao; moss from tree bark in forest canopy, moist deciduous forest.indicus\u2009=\u2009Indian. The name refers to the Indian subcontinent, where the new species was found. An adjective in the nominative singular.Etymology: From Latin Nebularmis burmensissp. nov. to 16.4% . Intraspecific variability ranged from 1.6 to 5.1%. It has been demonstrated that thresholds used in determining barcoding gaps differ greatly between various animal groups [Phylogenetic position. The species was inferred to be a sister species to ov. Fig.\u00a0. The p-dl groups , often el groups . ImportaNebularmis .See Table\u00a0N. auratussp. nov. (((N. reticulatus ((N. cirinoi (N. burmensissp. nov. + N. indicussp. nov.)))) \u2009+\u2009((N. cirinoi (N. burmensissp. nov. + N. indicussp. nov.))) . Node A2 does not conclusively identify the ancestral region for the clade ((N. reticulatus ((N. cirinoi (N. burmensissp. nov. + N. indicussp. nov.))), but the clade ((N. cirinoi (N. burmensissp. nov. + N. indicussp. nov.)) was inferred as having an Oriental origin in both trees (A3 and B3\u2009=\u2009100%), thus implying the dispersal of N. cirinoi to the Afrotropics. Node B2 is analogously inconclusive regarding the ancestral region for the putative sister species N. reticulatus and N. auratussp. nov.Two topologies were observed in the Bayesian analyses based on four datasets : ((()) Fig.\u00a0a and (()) Fig.\u00a0b. In botNebularmis by G\u0105siorek et al. [N. reticulatus and N. cirinoi examined at the time of its erection, supplied by the scarce and mostly dubious data from the original descriptions of other species known at the time.\u00a0While studying the description of Claxtonia crebraclava [N. bhutanensissp. nov. Thus, we concluded that Echiniscus crebraclava was incorrectly transferred to Claxtonia by G\u0105siorek et al. [Nebularmis crebraclavacomb. nov. Although Sun et al. [Nebularmis , as in Stellariscus [N. burmensissp. nov.), calling to mind the bumps in Echiniscus palmai [E. palmai shares some characteristics of Nebularmis: the intracuticular matrix is similar to the sponge layer or nomina inquirenda or junior synonyms (N. mihelcici) were also excluded. Importantly, the generic affinity of N. markezi is uncertain since eye pigment in this species was described by Mihel\u010di\u010d [Nebularmis specimens we examined before mounting in Hoyer\u2019s medium had red eyes, and no variability in this trait has been detected within any of the known echiniscid genera [Nebularmis , we excluded this species from the key until this ambiguity is resolved.The key provided below is mostly based on qualitative traits of sexually mature (adult) individuals. This is a usual practice in modern echiniscid taxonomy, as previous authors did not distinguish between different life stages. Consequently, larvae and juveniles are excluded from the key since they are not known for every species. Furthermore, representatives of nated in , 28 as nMihel\u010di\u010d as blackd genera . Pedal plates IV sculptured .................................................3Nebularmis indicussp. nov.\u2013. Pedal plates IV unsculptured ................................................................................................ Nebularmis bhutanensissp. nov.3(2). Secondary clavae greatly enlarged, micropores present in the scapular plate\u00a0.................................................................................................................. Nebularmis crebraclava \u2013. Secondary clavae not enlarged, micropores absent in the scapular plate ..................................................................................................................... Nebularmis cirinoi 4(1). Claw spurs heteronych ............................................................................................ \u2013. Claw spurs isonych ...........................................................5Nebularmis auratussp. nov.5(4). Claw spurs with blunt ends.................................. .................................................... \u2013. Claw spurs with acute ends ...................................................6A\u2009<\u200920% of the body length .................................. Nebularmis burmensissp. nov.6(5). Granules in the anterior portions of paired segmental plates in the shape of prominently convex bumps that are clearly separated; cirri A\u2009>\u200925% of the body length .......................................................................................................................Nebularmis reticulatus \u2013. Granules in anterior portions of paired segmental plates flattened and often merged; cirri Nebularmis in Asia is that of Murray [Nebularmis reticulatus from the Sikkim Himalayas, and the presence of this typical Palearctic species in this region cannot be dismissed since it was reported from the neighboring Nepal [N. reticulatus range. Specimens representing Nebularmis were found in Greenland [N. reticulatus. Even if N. reticulatus was indeed recorded in Greenland, anthropogenic dispersal would seem to be the most likely explanation. Although Greenland is traditionally regarded as a part of the Nearctic, its invertebrate fauna is largely a mixture of Palearctic, cosmopolitan and endemic taxa [N. reticulatus in Greenland would not affect the status of a principally Palearctic species [Nebularmis is certainly present in the Neotropical region [Nebularmis phocae requires a redescription [N. cirinoi [Nebularmis, which we examined, is different from all other Nebularmis spp. by its elongated and thin claws; thus, it most likely represents a new species.The oldest record of f Murray . He repong Nepal and lateng Nepal . Since treenland , but themic taxa , 77; thu species . Nebularl region , 36, butcription , and the cirinoi since weNebularmis specimens from the Ruwenzori Mountains and Doi Inthanon are unidentifiable due to their poor states. The dorsal plate sculpturing of the African material clearly resembles N. cirinoi and these specimens likely belong to this taxon, as each location from which specimens were reported was in a mountainous tropical rainforest . An undi et al. ), inhabitralasia , we hypoNebularmis is inferred herein as having an Oriental ancestry, which potentially renders this region vital for echiniscid diversification. However, Southeast Asia belongs to one of the worst-sampled areas of the globe, which is evidenced, for example, by the fact that three out of the four new Nebularmis species described in this study are also the first tardigrade records for Bhutan and Myanmar. As many post-Gondwana taxa seem basal with respect to the derived Laurasian fauna, they are important in the understanding of heterotardigrade phylogeny [Diploechiniscus, Proechiniscus, Multipseudechiniscus, Novechiniscus, Parechiniscus and Cornechiniscus, the last likely dispersed to Africa and South America, vs Antechiniscus, Mopsechiniscus and Barbaria, the last of which contains one species that dispersed to the southern Nearctic region [Nebularmis involves its relatively recent divergence and radiation away from the current centers of relic Gondwanan tardigrade faunal diversity [Southeast Asia has an intricate geological history, with the Indian subcontinent and Indochina considered a part of the Gondwanan paleocontinent that later joined the Laurasian Palearctic region \u201382. Nebuhylogeny , 83, 84.c region ). As Souiversity , 86.th Symposium on Tardigrada in Modena, mirroring the actions of rotiferologists [nomina inquirenda and species dubia embedded therein [Nebularmis can serve as a perfect example; of the eight valid species listed in the last edition of the checklist, no taxonomic obscurities were identified in only two species. The remaining six species are indistinguishable [Tardigrade taxonomy is burdened with the same problems as encountered in other meiofaunal groups that underwent preliminary study in the XVIII and XIX centuries, i.e.: a lack of type series, species descriptions considered by modern standards as insufficient and/or inadequate, difficulties with discerning intraspecific from interspecific variability, and lack of type DNA sequences , 28, 87.ologists , a propo therein , revealsuishable , 28; thuNebularmis represents yet another echiniscid genus in which dorsal sculpturing and claw morphology are crucial taxonomic criteria [Nebularmis with Stellariscus, the two genera are not directly related. Continental Asia is an important but mostly undersampled region in the context of echiniscid diversity and phylogeny. Finally, we propose enhancing efforts to eliminate dubious and/or unidentifiable water bear species from the modern professional literature by creating a list of available names.criteria , 90\u201393. Additional file 1.\u00a0Primers and DNA amplification protocols.Additional file 2.\u00a018S rRNA alignment.Additional file 3.\u00a028S rRNA alignment.Additional file 4.\u00a0ITS-1 alignment.Additional file 5.\u00a0ITS-2 alignment.Additional file 6.\u00a0COI alignment.Additional file 7.\u00a0Concatenated 18S + 28S + ITS alignment used for the biogeography reconstructions."} +{"text": "Nature Communications 10.1038/s41467-019-14173-3, published online 16 January 2020.Correction to: Since the publication of this work, M. Gad has changed their name from M.G. Elabd. This has now been amended in the HTML and PDF versions of the article."} +{"text": "Ischnothyreus Simon, 1893 from Xishuangbanna, Yunnan, China are recognized, including six new species: I.cristiformis Tong & Li, sp. nov. (\u2642\u2640), I.mangun Tong & Li, sp. nov. (\u2642\u2640), I.mengyang Tong & Li, sp. nov. (\u2642\u2640), I.peltifer , I.qidaoban Tong & Li, sp. nov. (\u2642\u2640), I.qiuxing Tong & Li, 2020 (\u2642\u2640), I.sijiae Tong & Li, sp. nov. (\u2640) and I.xiaolongha Tong & Li, sp. nov. (\u2642\u2640). The male of I.qiuxing Tong & Li, 2020 is described for the first time. Photos of the habitus and copulatory organs are provided.Eight species of the genus Oonopidae Simon, 1890 is a diverse spider family with 1872 extant described species in 114 genera. They have a nearly worldwide distribution but are most abundant in the tropics and subtropics were taken under high vacuum with a Hitachi TM3030 after critical point drying and gold-palladium coating. All measurements were taken using an Olympus BX51 compound microscope and are given in millimeters in the text. The specimens are preserved in Shenyang Normal University (SYNU) in Shenyang, China.The specimens were examined in 95% ethanol using a Leica M205C stereomicroscope. Details were studied with an Olympus BX51 compound microscope. Photos were taken with a Canon EOS 750D zoom digital camera (18 megapixels) mounted on an Olympus BX51 compound microscope. Vulvae were cleared in lactic acid. Scanning electron microscope images . Paratypes. 1\u2640: same data as for holotype (SYNU-380); 3\u26421\u2640: Xiaolongha, Xishuangbanna Biodiversity Conservation Corridor, Qidaoban, valley forest; 21\u00b024.808'N, 101\u00b037.874'E; 711 m; 18.VI.2013; Q. Zhao and Z. Chen leg. (SYNU-381\u2013384).I.mangun sp. nov. and I.xiaolongha sp. nov. by the lamella-like membrane of the male palp and short dorsal abdominal scutum, but can be distinguished by the large cockscomb-shaped sclerotized process , the broad rectangular-shaped retrolateral lobe of the bulb . The female differs from I.mangun sp. nov. and I.xiaolongha sp. nov. by the large bowl-shaped atrium .The new species is similar to ess Fig. of the mess Fig. in I.maess Fig. in I.xiulb Fig. . : habitus as in Fig. Carapace: 0.88 long, 0.65 wide; yellow, with egg-shaped patches behind eyes, surface of elevated portion of pars cephalica smooth, sides finely reticulate, lateral margin straight, smooth .Female . Paratype. 1\u2640: same data as for holotype (SYNU-386).I.cristiformis sp. nov. and I.xiaolongha sp. nov. in the lamella-like membrane of male palp and the short dorsal scutum of the abdomen, but can be distinguished by the unmodified male cheliceral fang , the narrow leaf-shaped retrolateral lobe of the male palp . The female differs from I.cristiformis and I.xiaolongha by the small rectangular-shaped atrium .The new species is similar to ang Fig. . : habitus as in Fig. Carapace: 0.81 long, 0.61 wide; yellow, with egg-shaped patches behind eyes, surface of elevated portion of pars cephalica smooth, sides finely reticulate, lateral margin straight, smooth .Female . Paratypes 5\u264212\u2640: same data as for holotype (SYNU-388\u2013404).I.taunggyi Tong & Li, 2020 in the male palp and the large, sclerotized process of male cheliceral fang, but can be distinguished by the broad retrolateral lobe of male palp . : habitus as in Fig. Carapace: 0.95 long, 0.78 wide; pale brown, with egg-shaped patches behind eyes, surface of elevated portion of pars cephalica smooth, sides finely reticulate, lateral margin straight, smooth .Female FDEB7CA9-2C62-5EA6-BCCF-45B99AD71CE3Ischnaspispeltifer Simon, 1892: 562.Ischnothyreuspeltifer : 21\u00b054.999'N, 101\u00b016.237'E; 561 m; 24.IV.2019; Y. Tong and J. Liu leg. (SYNU-414\u2013425).5\u26427\u2640: China, Yunnan, Xishuangbanna Tropical Garden; See Tropical Asia. Introduced to North, Central, South America, Britain, Gaboon, Seychelles, Madagascar, Hawaii.Taxon classificationAnimaliaAraneaeOonopidaeTong & Lisp. nov.06E0F524-B435-5589-9EF6-D994FB002536http://zoobank.org/C69A3DF7-810D-46A9-B76A-73DF6E02D327Holotype \u2642: China, Yunnan, Mengla City, Menglun Town, Xishuangbanna Natural Reserve, 55 Km, monsoon forest; 21\u00b057.531'N, 101\u00b011.961'E; 751 m; 13.VI.2013; Q. Zhao and Z. Chen leg. (SYNU-405). Paratypes. 1\u26425\u2640: same data as for holotype (SYNU-406\u2013411); 1\u26421\u2640: Xiaolongha, Xishuangbanna Biodiversity Conservation Corridor, Qidaoban, valley forest; 21\u00b024.808'N, 101\u00b037.874'E; 711 m; 18.VI.2013; Q. Zhao and Z. Chen leg. (SYNU-412\u2013413).I.auritus Tong & Li, 2012 in the long dorsal scutum of the abdomen and the helmet-shaped sclerotized process of the male cheliceral fang, but can be distinguished by the broad mushroom-like projection . : habitus as in Fig. Carapace: 0.84 long, 0.69 wide; dark brown, with egg-shaped patches behind eyes, surface of elevated portion of pars cephalica finely reticulate, sides strongly reticulate, lateral margin straight, smooth .Female .4\u26423\u2640: China, Yunnan, Menghai City, Mangun Stockaded Village, Xishuangbanna Natural Reserve, secondary forest; I.balu Kranz-Baltensperger, 2011 in the circular atrium in the female, but can be distinguished by the finger-shaped sclerotized process of the male cheliceral fang . BodyMale .Female . Paratype. 1\u2640: same data as for holotype (SYNU-427).I.tadfane Tong & Li, 2013 in the large dorsal scutum of the abdomen, but can be distinguished by the greater short winding tube of the endogyne . : habitus as in Fig. Carapace: 0.68 long, 0.54 wide; yellow-brown, without any pattern, surface finely reticulate, lateral margin straight, smooth . Paratypes 1\u2640: same data as for holotype (SYNU-429); 1\u26423\u2640: same data as for holotype; 21\u00b024.253'N, 101\u00b036.324'E; 761 m; 15.VI.2013; Q. Zhao and Z. Chen leg. (SYNU-430\u2013433).I.cristiformis sp. nov. and I.mangun sp. nov. in the lamella-like membrane of the male palp and the short dorsal scutum of the abdomen, but can be distinguished by the tongue-shaped sclerotized process , the broad leaf-shaped retrolateral lobe of the male palp and the small bell-shaped atrium .The new species is similar to ess Fig. of the cess Fig. in I.crang Fig. in I.maalp Fig. . : habitus as in Fig. Carapace: 0.80 long, 0.61 wide; yellow, with egg-shaped patches behind eyes, surface of elevated portion of pars cephalica smooth, sides finely reticulate, fovea absent, lateral margin straight, smooth .Female (paratype, Same as male except as noted. Body: habitus as in Fig. Carapace: 0.76 long, 0.63 wide. Mouthparts: chelicerae and endites unmodified. Abdomen: 0.95 long, 0.64 wide. Epigastric area: surface without external features (Fig. Endogyne: from the middle of the slightly thickened margin of the postgastric scutum runs a dark, simple winding tube posteriorly, ending in a small bell-shaped atrium (Fig. res Fig. . Endogynium Fig. .The specific name is a noun in apposition taken from the type locality.Known only from the type locality."} +{"text": "Scientific Reports 10.1038/s41598-021-82542-4, published online 03 February 2021Correction to: Rohit K. Srivastava was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cAuthor contributions S.E.W., Y.S., R.H.P., S.F.S., and S.A.V. designed experiments. S.E.W., Y.S., R.H.P., Z.C., A.P.S., R.K.S., A.M.I., S.R.L., A.B., Z.S., P.S., and S.A.V. performed experiments. S.E.W., Y.S., R.H.P., R.S.W., P.S., and S.A.V. analyzed and interpreted data. S.E.W. and S.A.V. wrote the manuscript and figures. S.E.W., K.B.G., D.A.A., D.L.T., and S.A.V. supervised the study. S.A.V. conceived of the study and procured funding.\u201dThe Acknowledgement section now reads:\u201cWe would like to thank Dr. Igor Stupin for assistance with MRI. We would like to thank Pamela Parsons in the Texas Medical Center Digestive Diseases Center for completing the immunohistochemistry experiments. The Texas Medical Center Digestive Diseases Center is supported by NIH grant P30DK56338. We would like to thank Aileron Therapeutics for their generous gift of the ATSP-7041 compound used in this work. This work was supported by a Texas Children\u2019s Department of Surgery Seed Award (S.A.V.), the Macy Easom Cancer Research Foundation Grant (S.A.V.), and a Cancer Prevention Research Institution of Texas (CPRIT) Multi-Investigator Research Award . This work was also supported in part by the European Union\u2019s Horizon 2020 Research and Innovation Programme under grant agreement 826121 (P.S.) and by National Cancer Institute Award R21CA223140 (P.S.).\u201dThe original Article has been corrected."} +{"text": "Rhipicephalus turanicus and their toxicity on human liver and kidney cells\u2019, Onderstepoort Journal of Veterinary Research 86(1), a1665. https://doi.org/10.4102/ojvr.v86i1.1665, the fourth author, Mbokota C. Khosa, was omitted from the \u2018Authors\u2019 and \u2018Affiliations\u2019 sections. The indicated author should be added as the fourth author, and the following affiliation should be added as his affiliation: Agricultural Research Council \u2013 Tropical and Subtropical Crops, Nelspruit, South Africa.In the published version of this article, Fouche, G., Adenubi, O.T., Leboho, T., McGaw, L.J., Naidoo, V., Wellington, K.W. et al., 2019, \u2018Acaricidal activity of the aqueous and hydroethanolic extracts of 15 South African plants against The Authors\u2019 contributions section is hereby update to:R. turanicus. K.W.W. wrote the first draft of the manuscript.G.F. conceptualised the study. M.C.K. was involved in the collection of some of the plant material and in the preparation of the extracts used in the biological screening assays. G.F., K.W.W. and T.L. performed the literature search and plant selection. T.L. prepared the plant extracts. M.C.K. was also involved in the fractionation and isolation process in the natural product chemistry laboratory. J.N.E. conceptualised the study in a joint application, and supervised the students and postdoctoral fellow. V.N. supervised determination of acaricidal activity. L.J.M.G. supervised the determination of cytotoxicity. O.T.A. determined the acaricidal activity against adult ticks of"} +{"text": "Drug Delivery. VOL. 24, NO. 1, pp. 1011\u20131017. https://doi.org/10.1080/10717544.2017.1344336.Zhang S, Huang C, Li Z, Yang Y, Bao T, Chen H, Zou Y and Song L. (2017). Comparison of pharmacokinetics and drug release in tissues after transarterial chemoembolization with doxorubicin using diverse lipiodol emulsions and CalliSpheres Beads in rabbit livers. When the above article was first published online, asterisk symbol (*) for the authors Shuisheng Zhang and Can Huang was missing which states that both the authors have contributed equally to this work. This has now been corrected in both the print and online versions."} +{"text": "Phoebe (Lauraceae) from southeastern Yunnan, China, which possesses more or less oblong leaves, paniculate inflorescences with strictly opposite lateral cymes, trimerous flowers with 4-locular stamens, and large fruits with tiny, equal, persistent tepals. Our molecular phylogenetic study based on nrITS, LEAFY and plastid matK sequences suggests that this species belongs to a clade of Phoebe including P.puwenensis, P.megacalyx, and P.macrocarpa. However, this species differs from the latter three species by subglabrous twigs, leaves and inflorescences , larger fruits (5\u20138 cm long vs. 1\u20134 cm long in the latter three species), and smaller tepals (1\u20132.5 mm long vs. 5\u201315 mm long in the latter two species). As a result, Phoebejinpingensis sp. nov. is described and illustrated here as new to science.We collected an unusual new plant of Lauraceae are woody plants, except for the hemiparasitic climber genus Cassytha L. , e.g. Alseodaphne Nees . The preserved flowers were dissected and observed, and photographs were taken under a stereo microscope (Leica S8APO).LEAFY and plastid matK sequences. This phylogeny included 40 species from five genera of the Persea group . Litseaacuminata (Blume) Sa. Kurata (Litseaakoensis Hayata (https://www.ncbi.nlm.nih.gov/genbank/). Vouchers and accession numbers of sequences are listed in Table To determine the systematic position of our new species, we conducted a phylogenetic study using nrITS, . Kurata and Litss Hayata were selLEAFY and plastid matK fragments, we followed Total DNA was extracted from silica-gel-dried leaves using Tiangen Plant Genomic DNA kits. To amplify the nrITS, BI) based on the concatenated sequences were carried out with MrBayes (ML) analyses were run with the IQtree , aligned using MAFFT 7 , and the MrBayes in Phyloe IQtree in Phylohttp://www.esri.com).The line drawing was done manually with a black ink pen. Illustrations and photos showing morphological characters were edited and merged in Adobe Photoshop CS2 ver. 9.0. Phylogenetic trees were browsed and adjusted in FigTree ver. 1.4.0 and thenExtinction risk was assessed using IUCN categories and criteria . PopulatTaxon classificationPlantaeColeopteraCerambycidaeBing Liu, Y.Yang, W.Y.Jin & Zhi Yangsp. nov.300D9704-7ACD-5B90-B9E9-2657AAC2C676urn:lsid:ipni.org:names:77218352-122\u00b037'N, 103\u00b001'E, elev. 956 m, 8 Apr 2014, B.Liu, Y.Yang, Q.W.Lin, L.Jiang & X.J.Li 2050 .China. Yunnan Province: Jinping County, Mengla, Tuomazhai, P.macrocarpa C.Y.Wu ; Jinping County, Mengla, Tuomazhai, 9 Oct 2011, fruit, B.Liu 1477 (PE!); Jinping County, Mengla, Tuomazhai, 14 Sep 2014, fruit, B.Liu, Y.Song, H.Lai & X.Yao 2417 (PE!).China. Yunnan Province: Jinping County, Mengla, Tuomazhai, 8 Apr 2014, fruit, 2. Fewer than 10 juvenile individuals were found. All the individuals have not been protected in any nature reserve, and a rubber plantation exists nearby the population. Based on IUCN Red List Categories and Criteria , the two clades within the genus were robustly supported (BS: 100 and PP: 1). Clade I consisted of P.puwenensis W.C.Cheng . Clade II includes P.angustifolia Meisn. Y.Yang & Bing Liu (P.chekiangensis C.B.Shang (P.formosana (Hayata) Hayata Nees (P.nanmu (Oliv.) Gamble (P.neurantha (Hemsl.) Gamble (P.sheareri (Hemsl.) Gamble (P.tavoyana (Meisn.) Hook.f. Hayata , P.lances) Nees , P.nanm) Gamble , P.neur) Gamble , P.shea) Gamble , and P. Hook.f. .Machilus was monophyletic (BS: 100 and PP: 1). Alseodaphnehuanglianshanensis H.W.Li & Y.M.Shui (Dehaasiaincrassata (Jack) Kosterm. , but relationships among them were not resolved. Alseodaphnopsis, a recently established genus, constituted a monophyletic group which received high support . Relationships among Alseodaphnopsis, Phoebe, and Machilus-Dehaasia-Alseodaphne were ambiguous.Y.M.Shui and DehaKosterm. were cloPhoebe, only a few molecular phylogenetic studies including partial sampling of the genus but high posterior probability . These phylogenetic studies consistently suggested that the traditional subdivision of the genus into two sections, i.e. sect.Phoebe and Caniflorae Meisn. and concealed and not obvious in well-developed swollen fruits and P.macrocarpa (3.5\u20134.2 cm long) , the bigger fruits (5\u20138 cm long vs. 3\u20134 cm long in the latter two species), and the smaller tepals (1\u20132.5 mm long vs. >5 mm long in the latter two species). Phoebepuwenensis also belongs to the same clade as P.jinpingensis in our phylogenetic trees. Our new species differs from P.puwenensis in the subglabrous twigs and leaves (vs. tomentose twigs and leaves in the latter species) and the bigger fruits (5\u20138 cm long vs. 1\u20132 cm long in the latter species). For taxonomic purposes, we provide a new key to these closely related species of clade I of the genus Phoebe.The genus cm long) . Our new"} +{"text": "Bandres\u2011Ciga, S. Saez\u2011Atienzar, J. J. Kim, M. B. Makarious, F. Faghri, M. Diez\u2011Fairen, H. Iwaki, H. Leonard, J. Botia, M. Ryten, D. Hernandez, J. R. Gibbs, J. Ding, Z. Gan\u2011Or, A. Noyce, L. Pihlstrom, A. Torkamani, A. R. Soltis, C. L. Dalgard, The American Genome Center, S. W. Scholz, B. J. Traynor, D. Ehrlich, C. R. Scherzer, M. Bookman, M. Cookson, C. Blauwendraat, M. A. Nalls, A. B. Singleton on behalf of the International Parkinson Disease Genomics Consortium, was originally published Online First without Open Access. After publication in volume 140, issue 3, page 341\u2013358 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to \u00a9 The Author(s) 2021 and the article is forthwith distributed under the terms of the \u201cCreative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The original article has been corrected."} +{"text": "Metabolites are appealing biomarkers in metabolic diseases, because a defective, disease\u2010related pathway may lead to accumulation or deficiency of certain metabolites. In this study, we combined three different non\u2010targeted serum metabolomics datasets in human and mice to explore pathways and biomarkers related to diabetes. In a comparative analysis between mice and men, we discovered metabolites related to a diabetic phenotype. We next assessed those biomarkers in another cohort of patients with type 2 diabetes (T2D). In mice and humans including a placebo\u2010controlled trial, we report the impact of sodium glucose cotransporter (SGLT) 2 inhibitor empagliflozin on previously identified glycemic marker 1,5\u2010anhydroglucitol .Full methods are described in detail in the Supporting Information. Db/Db mice and Db/+ control mice were fed a high\u2010fat diet \u00b1 empagliflozin.P\u2010value, both data sets showed a clear separation of diabetes versus non\u2010diabetes Figure\u00a0. AccordiIn a placebo\u2011controlled, randomized, double blind human trial Figure\u00a0,3 1,5\u2010In this manuscript, we used three different metabolomic data sets to study biomarkers and substrate utilization in relation to diabetes and glycemic control. Comparing human and mouse metabolomics, we found BCAA, glutathione and acylcarnitine metabolism as well as 3\u2010hydroxy fatty acids to be increased in humans and mice with diabetes (discussed in the Supporting Information). In addition, 1,5\u2010AG, a metabolite that has earlier been recognized as glycemic marker,1,5\u2010AG is structurally similar to glucose and has been recognized as short\u2010 to mid\u2010term marker of glycemic control in several studies.In conclusion, our translational approach gives novel insights into the metabolic profile associated with T2D. Particularly, our unbiased metabolomics identified 1,5\u2010AG as an excellent biomarker for glycemic control in humans and mice. We further demonstrate SGLT2 inhibition to lower 1,5\u2010AG serum levels, most likely mediated by reduced renal reabsorption. 1,5\u2010AG should consequently not be used as an indicator of glycemic control in patients with SGLT2 inhibitor treatment.All subjects gave written informed consent. Ethics of myocardial infarction cohort were approved by the ethical committee of Policlinico Tor Vergata University of Rome. Ethics of Empagliflozin registry cohort were approved by the ethics committee of the Medical Faculty of RWTH Aachen University. Ethics of the placebo\u2011controlled, randomized, double blind human trial with empagliflozin were approved by the ethics committee of the Medical Faculty of RWTH Aachen University and the German Federal Institute for Drugs and Medical Devices .Animal experiments were approved by the government of North Rhine\u2010Westphalia, Germany.The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.N.M. has received support for clinical trial leadership from Boehringer Ingelheim, Novo Nordisk, served as a consultant to Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, received grant support from Boehringer Ingelheim, Merck, Novo Nordisk, and served as a speaker for Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, and Astra Zeneca. N.M. declines all personal compensation from pharma or device companies.K.S. served as a consultant to Amgen, Boehringer Ingelheim, AstraZeneca, Lilly, received grant support from Boehringer Ingelheim, and served as a speaker for Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Novartis, OmniaMed.M.F. served as a consultant for Boehringer Ingelheim, Merck Sharpe&Dohme, Lilly & Co, Janssen, Sanofi, Amgen.M.L. received grants and personal fees from Boehringer Ingelheim, MSD and Novo Nordisk, personal fees from Amgen, Sanofi, Astra Zeneca, Bayer and Lilly.B.A.K. was supported by a grants from the Deutsche Stiftung f\u00fcr Herzforschung (DSHF)[F\u201043\u201016] and RWTH Aachen University (START); N.M. and M.L. were supported by the Deutsche Forschungsgemeinschaft . K.S., N.M. and M.L. were further supported by a CORONA Foundation grant. M.F. laboratory was in part funded by EU\u2010FP7 FLORINASH [grant agreement ID: 241913], Ministry of University (MIUR) Progetti di Ricerca di Interesse Nazionale (PRIN) [protocol number 2015MPESJS_004 and 2017FM74HK], Fondazione Roma call for Non\u2010Communicable Diseases NCD 2014, EU\u2010FP7 EURHYTHDIA [grant agreement ID: 278397]. The funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.Conceptualization, B.A.K., M.F., N.M., and M.L.; Methodology, B.A.K., M.F., and M.L.; Development or design of methodology, B.A.K., M.F., and M.L.; Software, B.A.K.; Formal Analysis, B.A.K., M.F., and M.L.; Investigation, B.A.K., J.M., K.T., M.R. A.A., J.A., B.G., K.S., F.R., R.S.; Untargeted metabolomics analysis, A.A., J.A.; Resources, B.A.K., M.F., and M.L.; Data Curation, B.A.K.; Writing \u2013 Original Draft, B.A.K.; Writing \u2013 Review & Editing, B.A.K., M.F., K.S., N.M., and M.L.; Visualization, B.A.K.; Supervision, M.F., N.M., and M.L.; Project Administration, B.A.K., M.F., N.M., and M.L.; Funding Acquisition, B.A.K, K.S., N.M., M.F., and M.L.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file."} +{"text": "Walled-off pancreatic necrosis is a challenging problem and pancreatic necrosectomy is associated with significant morbidity and mortality. Following necrosectomy, postoperative bile leak is a rare complication. We present such a case of delayed bile leak from the distal common bile duct in an 81-year-old lady following pancreatic necrosectomy, which was successfully managed by endoscopic stenting. Walled-off pancreatic necrosis can be managed by percutaneous catheter drainage, endoscopic, minimally invasive technique or open necrosectomy . FollowiAn 81-year-old female, a known case of idiopathic acute necrotizing pancreatitis, had been on percutaneous catheter drainage (PCD) for infected pancreatic necrosis at 6\u00a0weeks of onset . On the Following severe necrotizing pancreatitis, the most common cause for the bile leak either spontaneously or following surgery is the duodenal fistula , 4. RareThe most common cause of bilious output from the drain following pancreatic necrosectomy is duodenal fistula; however, a high index of suspicion of biliary fistula (though rare) from the bile duct should be made if the patient is well and tolerating feed.N.P. wrote the manuscript. L.A., K.B.D. and B.P. provided the images. N.P., L.A., K.B.D. and B.P. approved the final manuscript. N.P. is the article guarantor.None declared.None.Informed consent was obtained for this case report."} +{"text": "Nature Communications 10.1038/s41467-021-21769-1, published online 19 March 2021.Correction to: The original version of this Article omitted from the author list the fourth author Alexander S. Mikheyev, who is from the Ecology and Evolution Unit, OIST Graduate University, Okinawa, Japan, and the Research School of Biology, Australian National University, Canberra, Australia. The third author Yoann Portugal has the following additional affiliation: Ecology and Evolution Unit, OIST Graduate University, Okinawa, Japan. The fourth author Alexander S. Mikheyev and the fifth author Greg J. Stephens declare equal contributions. Consequently, the Acknowledgements, which formerly read \u201cWe thank Michael Iuzzolino, Dieu My thanh Nguyen, Orit Peleg, and Michael Smith for comments on the manuscript and code testing. This work was supported by the Okinawa Institute of Science and Technology Graduate University\u201d, have been corrected to \u201cWe are grateful to Takahashi Ikemiya for maintaining the experimental bee colonies. We thank Michael Iuzzolino, Dieu My Thanh Nguyen, Orit Peleg, and Michael Smith for comments on the manuscript and code testing. This work was supported by the Okinawa Institute of Science and Technology Graduate University. Additional funding was provided by KAKENHI grants 16H06209 and 16KK0175 from the Japan Society for the Promotion of Science to AM\u201d. Additionally, the Author Contributions, which formerly read \u201cY.P. performed the bee work and devised the imaging setup, L.H. devised the labeling tool, K.B. performed method development and data analysis, K.B. and G.S. designed the study and wrote the manuscript\u201d, has been corrected to \u201cY.P. performed the bee work, Y.P. and A.M. devised the imaging setup, L.H. devised the labeling tool, K.B. performed method development and data analysis, K.B., A.M., and G.S. designed the study, K.B. and G.S. wrote the manuscript\u201d. This has been corrected in both the PDF and HTML versions of the Article.The original version of the\u00a0Supplementary Information"} +{"text": "Wide hybridization in cereal crops is one of the most efficient tools for the enrichment of genetic variability and addressing a number of breeding problems related to resistance and tolerance to biotic and abiotic stresses. Therefore, a large number of amphidiploids between species possessing different morphological, genetic and physiological properties have been developed. One of the most valuable species with regard to the possibilities for introducing valuable traits and properties into wheat species is the wild Dasypyrum villosum. With the aim to study the androgenic response of the Triticum durum-D. villosum amphidiploids, two accessions and their parental forms \u2013 the durum wheat cultivars Gergana and Argonavt and a landrace of the D. villosum \u2013 were studied. The following parameters were determined: callus induction, plant regeneration, yield of albino and green regenerants. It was found that the callus induction of the two studied amphidiploids differed significantly from that of the parental forms (2.1\u20137.2 %), being significantly higher, 30.7 and 16.5 %, respectively. Regardless of the difference in callus induction, the amphidiploids did not significantly differ from the parental forms in their regeneration ability. The yield of albino plants exceeded the yield of green regenerants and followed the tendency observed in callus induction. Green plants were found only in the amphidiploid Gergana-D. villosum and in the parental form durum wheat Gergana. Plants were regenerated from the species D. villosum, although they were only albinos, showing its good responsiveness to anther culture. The established characteristics of the amphidiploids and their parental forms make their practical use highly valuable for the improvement of different types of cereal crops. The development of highly productive varieties of cultivatedplants, which at the same time are characterized with stableyields and are resistant to different biotic and abiotic stressfactors, is a primary task in plant breeding . However, the increase of yield within the genome ofa given species is not limitless . In thisrespect, there are different approaches to enrich the genome ofthe cultivated plants \u2013 wide hybridization, genetic engineering,genome editing technologies, etc. .Although contemporary science has reached high levels ofuse of the latter two technologies, wide hybridization remainsa main conventional tool for achieving high genetic variability.There is a large amount of research on amphidiploids de-velopedthrough wide hybridization among the cereal crops. One of the most promising species forenrichment of the genome of common and durum wheat,however, is Dasypyrum villosum. This species has been describedin detail with regard to the possibility of being used inthe improvement work on the wheat species in the researchesof A. Gr\u0105dzielewska (2006a) and C. De Pace et al. (2011).In another research, A. Gr\u0105dzielewska (2006b) described indetail a large number of studies on the production of hybrids,natural hybrids, substitution and addition lines with wheat andother species. There are a number of studies on the possibilityof using the hybrids and amphidiploids of the wheat specieswith D. villosum in practical breeding . A. Stefani et al. (1987)reported rather detailed morphological characteristics of theamphidiploid Triticum durum-D. villosum.Since plant breeding is a rather dynamic process, whendeveloping lines from the cereal species, the biotechnologicalmethod of anther culture is often used to accelerate thebreeding process . Differentresearchers report that the efficiency of the process and theproduction of a high number of green plants is related to theresponse to anther culture of the parental forms involved inthe cross . In this respect, the developedamphidiploids, substitution and addition lines withD. villosum, are specific parental forms, the reaction to antherculture of which has not been studied up to now. The possibilityto apply anther culture to amphidiploids in principle hasbeen little investigated. The response to anther culture in theamphidiploids has been studied in the amphidiploid Aegilopsvariabilis-Secale cereale , and the authorsdetermined 0.1\u201313.4 % of regenerants obtained from 100 androgenicembryoids. D. Plamenov et al. (2009) determined1.9\u20133.2 % of green regenerants from 100 cultured anthers inthe amphidiploid T. durum-T. monococcum ssp. aegilopoides.In tritordeum , it was also found out thatanther culture is an efficient process. The results from theseresearches showed that different amphidiploids are able togive positive response to anther culture.The aim of this study was to determine the reaction of theamphidiploid T. durum-D. villosum to anther cultivation incomparison to its parental forms.Plant material. Two accessions of the amphidiploid T. durum-D. villosum (1dv (Gergana-D. villosum) and 2dv (Argonavt-D. villosum)), a part of the collection of DobrudzhaAgricultural Institute were used, as well the durum wheatparental forms (T. durum cv. Gergana and cv. Argonavt) andthe wild species D. villosum.The accession of D. villosum (2n = 2x = 14 (VV); familyPoaceae, tribe Triticeae, subtribe Triticineae, genus Dasypyrum)was collected in Dobrich region in 2011.Crosses Gergana \u00d7 D. villosum and Argonavt \u00d7 D. villosumwere made conventionally, without embryo rescue in 2012;the obtained seeds (Gergana \u00d7 D. villosum \u2013 3 seeds and Argonavt\u00d7 D. villosum \u2013 8 seeds) were germinated and at tilleringstage the plants (Gergana \u00d7 D. villosum \u2013 1 plant and Argonavt\u00d7 D. villosum \u2013 3 plants) were treated with colchicine in2013. The seeds from the two obtained primary amphidiploidswere multiplied several timesAnther culture. The experiment was carried out during2016/2017. Anther donor plants were grown under greenhouseconditions. The seeds from the accessions were germinatedin Petri dishes and then planted in plastic pots. Fifteen plantsfrom each accession were grown in three pots, using 10 plantsper genotype. Primary, seedling were vernalized at 4 \u00b0C for 45 days. After this period,the plants were transferred to a cold greenhouse (5\u201315 \u00b0C) forabout three months, and the temperature was later increased to15\u201320 (25) \u00b0C. Tillers bearing spikes containing anthers withmicrospores at mid- to late uninucleate stage were cut, put ina vessel with water and pretreated at 4 \u00b0C for 8\u20139 days. Tenspikes from each genotype were collected. Cold pretreatedspikes were surface sterilized with 70 % ethanol under asepticconditions. Sixty anthers from each spike were placed intest tubes with 20 ml P2 induction medium . The anthers were cultured at 28 \u00b0C in darkness forabout 60 days. After the 30th day, they were periodicallychecked for induction of embryogenic structures , which were transferred to test tubes with 10 mlregeneration medium and cultured at 25\u00b0C . Green and albino regenerantswere counted after 30 days.The androgenic response was estimated by the followingtraits: callus induction (CI) , plant regeneration(PR) , frequency (yield) of greenplants (YGR) and frequency (yield) of albino plants(YAR) .Statistics. The obtained results were summarized overgenotypes and parameters. One way ANOVA was carriedout with the aim of determining the effect of the genotype onthe studied parameters to estimate their androgenic response.Significant differences between the amphidiploids and their parental forms were calculated based on the Duncan test. Toprocess the data, software MS Office Excel 2003 was used,and to perform ANOVA and the Duncan test \u2013 IBM SPSSStatistics v.19.The results on the androgenic potential of the investigatedamphidiploids and their parental forms (Table 1) showed thataccession 1dv had the highest callus induction (30.7 %), anddurum wheat Argonavt \u2013 the lowest (2.1 %). Between theparental forms, there were no significant differences (bothbetween the durum wheat cultivars and between the speciesdurum wheat and D. villosum). The two amphidiploids differedsignificantly by their callus induction, which was probablyrelated to the effect of the maternal component.The yield of green plants, averaged for the entire investigatedset, was extremely low. In the entire experiment, only 5green regenerants were produced, one of them being from thedurum wheat cultivar Gergana, and the other 4 \u2013 from the amphidiploid1dv (Gergana-D. villosum). No green regenerantswere obtained from cultivar Argonavt and from the amphidiploid2dv. Also, no green plants were produced from the wildspecies D. villosum. Although there was a rather small numberof the obtained plants for formulating a general tendency forthe effect of the parental forms, the presence of green plantsin cultivar Gergana and the amphidiploid, in which it wasinvolved, was probably due to genotypic specificity.The albino plants considerably exceeded the green regenerants.In practice, they were predominant with regard to thetotal number of regenerants. The amphidiploid 1dv again hadthe highest yield of albino plants (10.3 %), and the lowest valueswere observed in cultivar Argonavt (0.4 %). The tendencyin yield of obtained albinos largely followed the tendency ofcallus induction. The two amphidiploids significantly differedfrom the parental forms by their values, as well as betweenthemselves . Meanwhile, significantdifferences between the two durum wheat cultivarsand between the durum wheat and the wild species were notregistered. The higher yield values of the albino plants in theamphidiploid 1dv may be related to the higher responsivenessof cultivar Gergana, which was the maternal component ofthis amphidiploid, although the difference between Gerganaand Argonavt was not significant.On the whole, plant regeneration, expressed as a numberof regenerants per 100 embryogenic structures, was comparativelylow. The highest values were read in the two investigatedaphidiploids , and the lowest\u2013in the wild species D. villosum (13.0 %). This parameterdid not follow the tendency observed in the values of callusinduction and yield of green and albino regenerants. Therewere no significant differences between any of the studiedaccessions. However, higher plant regeneration was registeredin the amphidiploids, in comparison to cultivar Argonavt andthe wild species, and the difference with cultivar Gergana wasconsiderably lower. The differences not being significant wasan indication that the regeneration potential of all studied accessionswas practically identical, and the differences formedwere entirely random. The total number of regenerants, however,expressly followed the tendency of callus induction andyield of albino plants. The higher responsiveness to antherculture of the two investigated amphidiploids in comparisonto either of the parental forms could be clearly observed inthis parameter.The results from the analysis of the variance of the studiedparameters (Table 2) showed that the genotype had a significanteffect on the parameters callus induction and yield ofalbino regenerants. This allows supposing that the separateaccessions gave specific responses and that there are significantdifferences between them, as determined by the Duncantest that was carried out. At the same time, the effect of theseparate accessions on the plant regeneration and the yieldof green plants was not significant. Worth mentioning are accessionsGergana and Gergana-D. villosum, in which higherresponsiveness to anther culture was observed, in general.Nevertheless, these results do not give a definite answer tothe question of whether the amphidiploids are different as abiologically distinct organism from the two parental formswith regard to their androgenic response.When summarizing the results at the level of the species,a clear tendency of the amphidiploid T. durum-D. villosumhaving significantly higher callus induction and yield of albinoregenerants was evident (Table 3).Simultaneously, significant differences between the twoparental forms were not observed, the values of both parametersbeing significantly lower in them. The yield of greenplants from the parental forms and from the amphidiploid wasextremely low and did not allow forming a clear tendency.In this case, the production of green regenerants was ratherrandom, without observing significant differences betweenthe investigated species. Plant regeneration, at the levels of both genotype and species, did not differ as a tendency. Theobserved differences were not significant (see Tables 3 and 4),which indicated that the studied amphidiploid did not differfrom the parental forms by its regeneration capacity.Concerning the results obtained on the androgenic response ofthe used accessions, it should be emphasized, that no sourcewas found in world literature that would present data on theamphidiploid T. durum-D. villosum or the species D. villosum.An exception was the research of X. Chen et al. (1996), whosuggested applying the anther culture method on hybrids(not amphidiploids) of the F1 (T. durum \u00d7 D. villosum). Theseauthors reported successful production of amphidiploids,regenerated from colchicine-treated calli. At the same time,there are researches on the use of tissue cultures on three component hybrids T. aestivum \u00d7 (T. durum-D. villosum).H. Li et al. (2005) reported lines with high powdery mildewresistance obtained from such hybrids through the method ofembryo rescue and subsequent anther culture.D. Plamenov et al. (2009), when investigating the androgenicresponse of accessions from the amphidiploidT. durum-T. monococcum ssp. aegilopoides, came up withresultsdifferent from ours. The reported callus induction was3.3\u201311.7 % for the two studied accessions, the plant regenerationwas considerably higher, 33.8\u201368.4 %, respectively, andthe albino regenerants yield was 1.9\u20133.2 %. At the same time,the yield of green plants (0.4\u20130.8 %) was a little higher thanthe data we obtained in our experiment (0.0\u20130.7 %). Theseauthors reported a total of seven regenerated plants from bothaccessions, this parameter being significant, unlike the resultswe obtained. Using anther culture in the amphidiploidAe. variabilis-S. cereale, and P2 medium, A. Ponitka et al.(2002) observed 1.4\u201315.7 % of callus induction, and on C17medium \u2013 20.0\u201365.2 %. Subsequently, the authors reported0.1\u201313.4 % yield of green regenerants using 190-2 regenerationmedium. It was found out that the androgenic responsewas strongly dependent on the genotype, similar to the resultsof the experiment we conducted. Successful regeneration ofgreen plants through the method of anther culture has also beenreported for an aneupolyhaploid of Thynopyrum ponticum, for the amphidiploid Festuca pratensis-Lolium multif lorum and the amphidiploid Cyclamenpersicum-C. purpurascens .In contrast to these results, the parental forms were characterizedwith much lower androgenic response. This wasconfirmed by the absence of callus induction in Ae. variabilisand rye, reported by A. Ponitka et al. (2002), and also in thespecies T. monococcum ssp. aegilopoides in the research ofD. Plamenov et al. (2009). Durum wheat is also characterizedby weak androgenic response, in general. M. Do\u011framac\u0131-Altuntepe et al. (2001), using 10 durum wheat genotypes,obtained only 248 green regenerants from 86,400 anthers(0.29 %). F. J\u2019Aiti et al. (1999), investigating 15 durum wheatgenotypes and 7500 cultivated anthers, obtained just threealbino regenerants and one green plant.L. Cist\u00fae et al. (2006), on the other hand, reported significantlyhigher production of green plants, but including6-benzylaminopurine or 6-furfurilaminopurine in the inductionmedium (C17). In more recent researches, the productionof haploids, even by the method of isolated microspores, hasbeen of extremely low efficiency in durum wheat . These results entirely corresponded to the datawe obtained with regard to the two cultivars Argonavt andGergana. Clear genotypic specificity was observed in the betterresponse of Gergana to anther culture as compared to Argonavt,although the difference was not statistically significant. Itis probable that this tendency is the reason for the amphidiploidGergana-D. villosum having better responsiveness to antherculture. In this respect, the amphidiploid T. durum-D. villosumwe investigated, and the amphidiploids reported byA. Ponitka et al. (2002) and D. Plamenov et al. (2009) werecloser by their androgenic response to the response of triticale than to the response ofthe parental forms. J. Pauk et al. (2000), K. Marciniak et al. (2003), C. Lantos et al. (2014) and H. Stoyanov et al. (2019)demonstrated that in triticale the albino regenerants are oftenpredominant, similar to the amphidiploid we studied. Thevalues of the green regenerants in triticale also varied , according to datafrom various researches .In contrast to the above responses of the parental formsAe. variabilis, S. cereale and T. monococcum ssp. aegilopoides,our study, although limited in volume, demonstrated thecomparatively good responsiveness of the species D. villosumto anther culture. This is the first time when results on regenerantsfrom this species are beingreported. At the same time, it should be emphasized that untilthis moment results from testing of the reaction of D. villosumto the anther culture method have never been reported. Thisis highly significant for the breeding of the wheat speciessince it would allow transferring genes from the wild speciesthrough the methods of wide hybridization and anther culturemore easily, quickly and efficiently. X. Chen et al. (1996) andC. Li et al. (2000) reported common wheat lines resistant topowdery mildew, which were obtained by crossing commonwheat to the amphidiploid T. durum-D. villosum, followed byembryo rescue and anther culture. Such results showed that thecombination of wide hybridization with the method of antherculture is an efficient tool that can be used in the breeding ofdifferent cereal crops.Based on the presented results, the following conclusionscould be made:1. For the first time, results on the androgenic response of the amphidiploid T. durum-D. villosum andof the parental component D. villosum are being reported.2. The callus induction of the two studied amphidiploidsdiffered significantly from that of the parental forms(2.1\u20137.2 %), being considerably higher \u2013 30.7 and 16.5 %,respectively.3. The plant regeneration of the investigated accessions variedwithin a certain range (13.0\u201335.9 %), the differences notbeing statistically significant. This indicated that in spite ofthe differences in the callus induction, the amphidiploidsdid not practically differ from the parental forms by theirregeneration capacity.4. Although plant regeneration was observed in all studiedaccessions, the yield of albino plants considerably exceededthe yield of green regenerants and followed the tendencyobserved in callus induction \u2013 the two amphidiploids hadsignificantly higher values. At the same time, green plantswere registered only in the amphidiploid Gergana-D. villosumand in the parental form durum wheat Gergana. Suchresults emphasized the genotypic specificity of the responseto anther culture5. Plants were regenerated from the species D. villosum,although only albinos, which indicated its good responsivenessto anther culture. 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Zeszyty ProblemowePostepow Nauk Rolniczych (Poland). 2001;474:47-54. (in Polish)"} +{"text": "Adv. Sci. 2020, 7, 190248710.1002/advs.201902487DOI: In this originally published version of this article, the cryo\u2010TEM image in Supporting Information Figure"} +{"text": "Mucosal Immunology 10.1038/s41385-020-00371-6, published online 14 January 2021Correction to: The article Hypoxia enhances ILC3 responses through HIF-1\u03b1-dependent mechanism, written by J. L. Fachi, L. P. Pral, J. A. C. dos Santos, A. C. Codo, S. de Oliveira, J. S. Felipe, F. F. F. Zambom, N. O. S. C\u00e2mara, P. M. M. M. Vieira, M. Colonna and M. A. R. Vinolo, was originally published electronically on the publisher\u2019s internet portal on 14 January 2021 without open access. With the author(s)\u2019 decision to opt for Open Choice the copyright of the article changed on 18 March 2021 to \u00a9 The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.The images or other third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.http://creativecommons.org/licenses/by/4.0/To view a copy of this licence, visit"} +{"text": "Front. Pharmacol. 12:753727. doi:10.3389/fphar.2021.753727.\u201dIn the original article, there was a mistake in the citation as published. In the citation, commas were missing between \u201cHe Y-Y and Xie X-M, Xie X-M and Zhang H-D, Zhang H-D and Ye J, Pang X-B and Jing Z-C, Jing Z-C and Yan Y\u201d. The corrected citation should be In addition, there was a mistake in Figure 6 as published. The x-axis labels for The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The \u201cHospital Universitario La Princesa Index\u201d (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels. Routine management of rheumatoid arthritis (RA) using the treat-to-target and tighTo overcome these limitations, the \u201cHospital Universitario La Princesa Index\u201d (HUPI), was developed and validated \u201310. HUPINowadays, the importance of an early diagnosis and treatment in patients with RA is well-established , 13. HowThis study is a secondary data analysis of an early arthritis cohort and an RCT in established RA.The main characteristics of the ACT-RAY trial have been previously reported . In summThis prospective cohort has been previously described . In summDemographics, disease activity measures, and radiological data are routinely recorded in standardized forms. In addition, biological samples are systematically collected. Patients are treated according to their treating rheumatologist's criteria.For the present study, we included patients either meeting the 1987 ACR criteria for RA or classPhysical function: It was measured through the Health Assessment Questionnaire-Disability Index (HAQ) in both datasets. This self-reported questionnaire was administered at every follow-up visit using cross-cultural validated versions , 20.\u00aeHS ELISA, R&D Systems\u00ae) according to the manufacturer's instructions as previously described according to the manufacturer's instructions.IL-6 was measured as a surrogate for inflammation only in Plain X-rays were available to measure radiographic progression using the Genant-Sharp score in ACT-RAY and the Disease activity indices included DAS28-ESR, SDAI, and HUPI and were calculated as follows:*\u221a(TJC28) + 0.28*\u221a(SJC28) + 0.70* ln(ESR) + 0.014*(GDAPat). TJC28 and SJC28 refer to the count of tender and swollen joints in 28 joints while GDAPat does so for the patients' global disease assessment and non-normally distributed variables as the median and interquartile range (IQR). Categorical variables were presented as numbers and proportions.To assess the performance of HUPI, DAS28, and SDAI on explaining changes in the three mentioned outcomes, we developed models for each of them as dependent variable adjusting for known potential confounders, such as age and sex . Only paR2 parameter and the quasi-likelihood under the independence model criterion (QIC) , nesting visits to each patient. An unstructured variance-covariance matrix for fixed and residual terms was used to avoid assumptions on the variance-covariance structure. Models were ranked according to the on (QIC) . The modWe used a similar approach to develop models for IL-6 serum levels as the dependent variable. As IL-6 levels were not collected in ACT-RAY, we used 80% of the PEARL population to establish the predicting model and the remaining 20% for its validation. This analysis was done with the R package \u201cgeepack\u201d .R2 parameter (R package stats) and the AIC (Akaike's Information Criterion) , 31, bei r2glmm) . Linear r2glmm) .This is a secondary analysis of anonymized data from patients included in the ACT-RAY and PEARL studies. The ACT-RAY trial was approved by the Ethics committees of each participant center (see Acknowledgement section \u201cACT-RAY group\u201d) and the PEARL study was approved by the Ethics Committee for Clinical Research at the Hospital Universitario de La Princesa . All patients had signed a written consent form before inclusion. Both studies were conducted according to the principles of the Helsinki Declaration .n = 1,084), 80% of patients were women, and 29% current smokers. Patients in the RCT presented higher HAQ and disease activity at baseline than their counterparts in the early arthritis cohort.The analysis included 8,090 visits from 550 patients in ACT-RAY and 775 visits from 534 patients in PEARL. Nonetheless, different numbers of visits/patients were assessed for each model, based on the availability of data for the involved variables (see further details in each table). Patients' demographic and clinical characteristics are presented in R2 (0.351) and the lowest QIC (1989.790) compared to the models using SDAI and DAS28 indicating that the former explained 35% of the HAQ variance, while the latter two indices explained ~33%. In the same line, the \u03b2 coefficient for HUPI was 0.365 vs. 0.344 and 0.343 for DAS28 and SDAI, respectively. The R2 parameters of all models remained similar in the validation cohort. Other parameters of each model are shown in The model fitted to explain HAQ adding HUPI as a predictor presented the highest R2 of 0.208 (QIC: 289.207) and 0.205 (QIC: 290.823), respectively, in comparison with an R2 of 0.190; QIC: 295.610 for DAS28 , as opposed to the SDAI model, which changed from explaining ~21% in the initial population to 18% in the validation population , followed by the one with DAS28 and then the one using SDAI . These results indicate that the HUPI model explained slightly better the variance of \u0394 erosions (3.4%) than the models including DAS28 and SDAI . When assessing partial R2 parameters for each explanatory variable, HUPI and HUPI2 explained 2% of the variance, while DAS28/DAS282 explained 1% and SDAI/SDAI2 0.2%. \u03b2 coefficients for HUPI and HUPI2 were 1.472 and 1.632 vs. 1.675 and 0.266 for DAS28/DAS282 and 0.759 and \u22120.042 for SDAI/SDAI2, respectively. Additional data are shown in As radiographic progression was evaluated using different methodologies in both studies, we ran separate comparative analyses. As shown in R2: 0.030 (0.010\u20130.150) AIC: 347.520) for DAS28, R2: 0.023 (0.008\u20130.138) AIC: 348.413 for HUPI, and R2: 0.018 (0.007\u20130.131) AIC: 348.955 for SDAI. The model including DAS28 explained ~3% of the variance, while those with HUPI and SDAI explained 2.3% and 1.8%, respectively. Partial R2 parameters show that DAS28/DAS282 explained 2.5% of the overall variance, while HUPI and SDAI explained 1.7 and 1.3%, respectively. Additional details are shown in In contrast, when using data from PEARL, none of the models were associated with radiographic progression. Results were In this study, we evaluated the performance of HUPI in comparison to other traditional disease activity indices as explanatory variables for physical function decline measured by HAQ, inflammation, assessed by IL-6 serum levels, and radiographic progression measured by \u0394 erosions. Our results indicate that HUPI performed well with most outcomes studied, being the best in explaining the decline in physical function and radiographic progression (ACT-RAY) and second-best for IL-6 serum levels. Of note, all indices performed poorly with regard to radiographic progression, mainly because both populations showed modest changes in their respective radiographic scores, as expected for early diagnosed, intensively treated patients.Even though the models containing HUPI did not outperform their counterparts in all comparisons, they were the most consistent in the different proposed scenarios. The SDAI models performed best for IL-6 changes, probably because the weight of CRP is high in SDAI but were the last ranked for \u0394 erosions. Similarly, DAS28 models worked best for explaining \u0394 erosions in PEARL but rated the worst for HAQ and IL-6.r = 0.45\u20130.47) for the former, and weaker for the latter cohort (r = 0.26\u20130.31). Another study pooling data from three RCTs showed moderate to good correlations with HAQ for SDAI and CDAI at baseline and after 6 months of follow-up (r = 0.36\u20130.66) has been previously analyzed in a study by Aletaha et al. with twor = 0.3) with the Ritchie Activity Index. In our study, initial models including all three indices performed similarly, with little differences favoring those including SDAI (with R2 parameters ranging from 0.190 to 0.208). Notably, when validating these models with the 20% remaining data from PEARL, HUPI and DAS28 models performed better than SDAI.The association between indices and IL-6 levels has also been previously analyzed in a study by Madhok et al. showing Navarro-Comp\u00e1n et al. summarizAletaha et al. assessedOur study has strengths, such as a study population including patients with both early and established RA, as well as a thorough statistical analysis. Nonetheless, it also presents some limitations, the most important being the low radiographic progression observed in both cohorts, which might have affected the performance of the three disease activity indices. This prevented us from establishing firm conclusions from the comparative analysis. Another limitation is the fact that IL-6 serum levels were only available from PEARL, something that limited the number of visits/patients assessed.In conclusion, HUPI exhibits a slightly superior performance to identify physical function declines and radiographic progression than DAS28 and SDAI and detects changes in IL-6 serum levels similar to the other indices. This behavior is consistent in early and established RA. These new findings, in addition to the absence of sex bias and the possibility of its calculation either with CRP or ESR, reinforce the role of HUPI for research purposes.www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available in https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx. For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.html\u201d. Requests to access these datasets should be directed to ACT-RAY data: www.clinicalstudydatarequest.com. PEARL data: Isidoro Gonzalez-Alvaro, isidoro.ga@ser.The data analyzed in this study is subject to the following licenses/restrictions: Data from the PEARL study can be requested to the corresponding author. Data from ACT-RAY were provided by Hoffmann-La Roche Ltd through a data-sharing agreement that does not allow for the public sharing of these data. The authors did not enjoy any special access privileges in gaining access to these data. Regarding the possibility that any other researcher would like to request data to replicate the reported study findings, Hoffmann-La Roche Ltd has implemented a Data Sharing policy to align with the ICMJE recommendations: \u201cQualified researchers may request access to individual patient-level data through the clinical study data request platform . Both studies were conducted according to the principles of the Helsinki Declaration. The patients/participants provided their written informed consent to participate.IG-\u00c1, SR-G, and NM contributed to conception and design of the study and organized the database. NM performed the statistical analysis and wrote a section of the manuscript. SR-G wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.maxime.dougados@cch.ap-hop-paris.fr; Huizinga, T. Leiden University Medical Center, Netherlands. E-mail: T.W.J.Huizinga@lumc.nlLead authors: Dougados, M. CHU Paris Centre\u2014H\u00f4pital Cochin. France. E-mail: Abu Shakra, M. Soroka Medical Center. IsraelAlberts, A. West Broward Rheumatology Associates, Inc. United StatesAlperi Lopez, M. Hospital Univ. Central de Asturias. SpainAmital, H. Chaim Sheba Medical Center. IsraelAringer, M. Universitatsklinikum \u201cCarl Gustav Carus\u201d. GermanyAslanidis, S. Hippokratio Hospital. GreeceBerenbaum, F. H\u00f4pital Saint Antoine. FranceBijlsma, H. Academisch Medisch Centrum Utrecht. NetherlandsBlanco-Garcia, FJ. Complejo Hospitalario Universitario A Coru\u00f1a. SpainBliddal, H. Frederiksberg Sygehus. DenmarkBorofsky, M. Clinical Research Center of Reading. United StatesBrocq, O. Ch Princesse Grace. MonacoBuldakov, S. Republican Clinicodiagnostic Center. Russian FederationCantini, F. Presidio Ospedaliero Misericordia e Dolce. ItalyCarre\u00f1o-Perez, L. Hospital General Universitario Gregorio Mara\u00f1on. Spain Chahade, W. Hospital Estadual do Servidor Publico. BrazilCiconelli, R. Universidade Federal de S\u00e3o Paulo. BrazilCodreanu, C. Centrul de Boli Reumatismale Dr. Ioan Stoia. RomaniaDahlqvist, SR. Norrlands Universitary Hospital. SwedenDamjanov, N. Institut Za Reumatologiju. SerbiaDiamantopoulos, A. S\u00f8rlandet Sykehus Kristiansand. NorwayDimdina, L. Clinical University Hospital Gailezers. LatviaDimic, A. Institut Za Prevenciju, Lecenje I Rehabilitaciju. SerbiaDorokhov, A. State Institution of Health Care\u2014Territorial Clinical Hospital. Russian FederationDubikov, A. City Clinical Hospital # 2. Russian FederationFadienko, G. Glpu Tjumen Regional Clinical hospital #1. Russian FederationFan\u00f8, N. Sj\u00e6llands Universitetshospital, K\u00f8ge. DenmarkFerreira, G. Hospital das Clinicas\u2013UFMG. BrazilGabrielli, A. Uni Politecnica Delle Marche; Ist. Di Clinica Medica Generale Ematologia Ed Immunologia Clinica. ItalyGaffney, K. Norfolk & Norwich Hospital. United KingdomGaudin, P. Hopital Sud. FranceGerlag, DM. Academisch Medisch Centrum. NetherlandsGerli, R. Osp S. Maria Misericordia Dip. ItalyGon\u00e7alves, CR. Hospital das Cl\u00ednicas\u2013FMUSP. BrazilHansen, MS. Gentofte Hospital. DenmarkHanvivadhanakul, P. Thammasat University Hospital. ThailandH\u00f8ili, C. Sykehuset Ostfold Moss HF. NorwayHou, A. Inland Rheumatology; Clinical Trials, Inc. United StatesHunter, J. Gartnavel General Hospital. United KingdomIlic, T. Clinical Centre of Vojvodina. SerbiaIonescu, R. Spitalul Sf Maria. RomaniaKaine, J. Sarasota Arthritis Center. United StatesKakurina, N. Clinical Hospital of Daugavpils. LatviaKamalova, R. Republican clinical hospital. Russian FederationKelly, T. Innovative Health Research. United StatesKnyazeva, L. GMU Kursk Regional Clinical Hospital. Russian Krumina Federation, L. L.Krumina GP practice. LatviaKurthen, R. Praxis Dr. med. Reiner Kurthen. GermanyLagrone, RP. St. Thomas Hospital. United StatesLapadula, G. Ospedale Policlinico Di.M.I.M.P. ItalyLavrentjevs, V. P.Stradins Clinical University Hospital. LatviaLawson, JG. Piedmont Arthritis Clinic. United StatesLazic, Z. Clinical Center Kragujevac. SerbiaLejnieks, A. Rakus Clinic Linezers. LatviaLevy, Y. Meir Medical Center. IsraelLexberg, \u00c5. Drammen sykehus Vestre Viken HF. NorwayMader, R. Haemek Hospital. IsraelMariette, X. Ch De Bic\u00eatre. FranceMarkovits, D. Rambam Medical Center. IsraelMartin Mola, E. Htal. La Paz. SpainMaugars, Y. Hopital Hotel Dieu Et Hme. FranceMaymo Guarch, J. Hospital del Mar. SpainMazurov, VI. Sbei Of Hpe \u201cNorthwestern State Medical University N.A. I.I.Mechnikov\u201d. Russian FederationMikkelsen, K. Revmatismesykehuset. NorwayMorovic Vergles, J. Clinical Hospital Dubrava. CroatiaNabizadeh, S. Martina Hansen Hospital. NorwayNanagara, R. Khon Kaen University. ThailandNasonov, EL. Fsbi \u201cScientific Research Institute of Rheumatology\u201d Of Russian Academy Of Medical Sciences. Russian FederationNavarro-Sarabia, F. Hospital Universitario Virgen Macarena. SpainNeumann, T. Universitatsklinikum Jena. GermanyNovak, S. Rheumatology and Clinical Immunology. CroatiaOlech, E. Oklahoma Medical Research Foundation. United StatesOza, M. Arthritis/Osteoporosis Treatment Center. United StatesParan, D. Sourasky / Ichilov Hospital. IsraelParsik, E. North Estonian Regional Hospital. EstoniaPegram, S. Rheumatic Disease Clin Res Ctr. United StatesPombo-Suarez, M. Hospital Nuestra Se\u00f1ora de la Esperanza. SpainPopova, T. Municipal Autonomous Institution of Healthcare \u201cCity Clinical Hospital #40\u201d. Russian FederationPuechal, X. Ch Du Mans. FranceRaja, N. Agilence Arthritis and Osteoporosis Medical Center, Inc. United StatesRidley, D. St. Paul Rheumatology. United StatesRosner, I. Bnei Zion Medical Center. IsraelRubbert-Roth, A. Klinik der Uni zu Ko ln. GermanyRudin, A. Sahlgrenska Universitetssjukhuset. SwedenSaraux, A. H\u00f4pital La Cavale Blanche. FranceSaulite-Kandevica, D. D.Saulite-Kandevica Private Practice. LatviaSettas, L. Ahepa Hospital. GreeceSfikakis, P. Laiko General Hospital. GreeceSheeran, T. Cannock Chase Hospital. United KingdomSizikov, A. FSBI Scientific Research Institute of Clinical Immunology of SB of RAMS. Russian FederationStamenkovic, D. Clinical Hospital Centre Rijeka. Croatia Stefanovic, D. Military Medical Academy. SerbiaStolow, JB. Texas Arthritis Research Center. United StatesTan, AL. Chapel Allerton Hospital. United KingdomTebib, J. Ch Lyon Sud. FranceTishler, M. Assaf Harofe. IsraelTony, HP. Universitatsklinikum W\u00fcrzburg. GermanyTroum, OM. United StatesUaratanawong, S. Vajira Hospital. ThailandUcar Angulo, E. Hospital de Basurto. SpainValenzuela, G. Berma Research Group. United Statesvan der Laken, K. VU Medisch Centrum. NetherlandsVan Laar, J. School of Clinical Medical Services. United KingdomVan RIEL, P.L.C.M. Akademisch Ziekenhuis St. Radboud. Netherlands Vasilopoulos, D. Hippocrateio Hospital of Athens. GreeceVeldi, T. East Tallinn Central Hospital. EstoniaVinogradova, I. State Institution of Healthcare Ulyanovsk Regional Clinical Hospital. Russian FederationVosse, D. Academisch Ziekenhuis Maastricht. NetherlandsWassenberg, S. Evangelisches Fachkrankenhaus. GermanyWeidmann, C. Medvin Clinical Research. United StatesWeitz, M. Center For Arthritis. United StatesWollenhaupt, J. Scho n Klinik Hamburg-Eilbek Klinik f\u00fcr Rheumatologie. Germany Xavier, R. Hospital das Clinicas\u2013UFRGS. BrazilYakupova, S. Kazan State Medical University. Russian FederationZagar, I. Klinicki Bolnicki Centar Zagreb. CroatiaZavgorodnaja, T. P.Stradins Clinical University Hospital. LatviaZemerova, E. Khanty-Mansiysk Autonomous Area\u2014Ugri Region Clinical Hospital. Russian FederationZisman, D. Carmel Hospital. IsraelZonova, E. FSBI Scientific Research Institute of Clinical and Experimental Lymphology of SB of RAMS. Russian Federa.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Haemonchus contortus\u2019, Onderstepoort Journal of Veterinary Research 83(1), a1164. https://doi.org/10.4102/ojvr.v83i1.1164, the sixth author, Mbokota C. Khosa, was omitted from the \u2018Authors\u2019 and \u2018Affiliations\u2019 sections. The indicated author should be added as the sixth author, and the following affiliation should be added as his affiliation: Agricultural Research Council \u2013 Tropical and Subtropical Crops, Nelspruit, South Africa.In the published version of this article, Fouche, G., Sakong, B.M., Adenubi, O.T., Pauw, E., Leboho, T., Wellington, K.W. et al., 2016, \u2018Anthelmintic activity of acetone extracts from South African plants used on egg hatching of The Authors\u2019 contributions section is hereby update to:G.F. conceptualised the study. M.C.K. was involved in the collection of some of the plant material and in the preparation of the extracts used in the biological screening assays. G.F., K.W.W. and T.L. carried out the literature search and plant selection. T.L. prepared the plant extracts. J.N.E. and E.P. arranged for sheep to be infected, collected the eggs and guided the study. B.M.S. performed the egg hatch assay on the extracts. M.C.K. was also involved in the fractionation and isolation process in the natural product chemistry laboratory. O.T.A. screened the extracts for toxicity on Vero cells. K.W.W. wrote the first draft of the manuscript.This correction does not alter the study\u2019s findings of significance or the overall interpretation of the study results. The authors apologise for any inconvenience caused."} +{"text": "Camellia are summarized with their types clarified. Camelliastrum and Desmitus are lectotypified and Salceda is neotypified. \u201cKailosocarpus\u201d and \u201cParapiquetia\u201d were not validly published, Theaphylla and Tsia are illegitimate replacement names for Thea, and Kemelia and Tsubaki are illegitimate replacement names for Camellia. Nomenclatural notes on Theopsis and its type are also provided.All the known generic synonyms of Camellia L. for the ornamental species, Camelliajaponica L. He referenced C.japonica without citing any specimens in the protologue . Accordingly, this illustration serves as the type of Camellia.Camellia have been gradually enlarged by several taxonomists . \u201cKailosocarpus\u201d and \u201cParapiquetia\u201d have no status under Art. 12.1 of the ICN and are, therefore, excluded from Table Camellia are elaborated below.Since the latest monograph of Camellia , two fur Perrier and Dank Gagnep. , have beCamellia , 1965 anCamellia are listocarpus\u201d : 170 andiquetia\u201d : 170 weriquetia\u201d : 12 in tTaxon classificationPlantaeEricalesTheaceae\ufeff1.Nakai, J. Jap. Bot. 16: 699. (1940)98C32C99-C667-53EA-9D3C-20632C2D9E35Camelliastrumcaudatum Nakai.: Camelliastrum to categorize six species in China and Japan, including Camelliastrumassimile (Champ. ex Benth.) Nakai, Camelliastrumbuisanense (Sasaki) Nakai, Camelliastrumcaudatum, Camelliastrumgracile (Hemsl.) Nakai, Camelliastrummairei (H.L\u00e9v.) Nakai and Camelliastrumsalicifolium (Champ.) Nakai, but did not designate a type. Based on the description in the protologue, Camelliastrumcaudatum is selected as the type of the genus. The basionym of Camelliastrumcaudatum, Camelliacaudata Wall., was lectotypified by H. Bruce s.n. in Wallich 978 (right-hand specimen of K001110475. An image is available at http://www.kew.org/herbcatimg/680707.jpg). Therefore, this specimen becomes the type of Camelliastrum (Art. 10.1 of the ICN).Taxon classificationPlantaeEricalesTheaceae\ufeff2.Raf., Sylva Tellur. 139. (1838)1364F261-B2CA-57A6-950F-D3DEB09EA5B0Desmitusreticulata (Lindl.) Raf. \u2261 Camelliareticulata Lindl., Bot. Reg. 13: t. 1078 (1827).(designated here): Lindl., Bot. Reg. 13: t. 1078 (1827).Desmitus for D.reticulata. This was a new combination based on C.reticulata because he referenced the basionym by the words \u201cCamel. do bot. reg. 1978...\u201d. However, the taxon number cited by C.reticulata based on the living plants that bore semidouble flowers and introduced from China. No specimen was cited in the protologue of C.reticulata. The coloured drawing, t. 1078, was accompanied by the protologue and therefore designated as the lectotype of C.reticulata. Accordingly, the drawing serves as the type of Desmitus (Art. 10.1 of the ICN).Taxon classificationPlantaeEricalesTheaceae\ufeff3.Blanco, Fl. Filip. ed. 2: 374. (1845)3F90E0B0-B5E4-5C14-89F4-081176700977Salcedamontana BlancoRamos & Eda\u00f1o 34071 .(designated here): Philippines. Luzon: Bulacan, Angat, February 1919, Salceda for S.montana. Thea as T.montana (Blanco) Merr. and stated that \u201cBlanco\u2019s specimens were from Angat, Province of Bulacan\u201d. However, the types of Blanco\u2019s species were suggested to be either all destroyed (S.montana. Based on the protologue (Ramos & Eda\u00f1o 34071 (K), is designated as the neotype of S.montana because it bears flower fragments and seeds on the sheet.estroyed : 6 or noestroyed : 5. I alotologue : 374, a Thea L., a genus established by T.sinensis L., currently C.sinensis [L.] Kuntze), was treated as a synonym of Camellia by Theaphylla Raf. and Tsia Adans. are illegitimate replacement names for Thea because Thea was cited in the synonymies of them . Similarly, Kemelia Raf. and Tsubaki Adans. are illegitimate replacement names for Camellia . Therefore, the four names, Kemelia, Theaphylla, Tsia and Tsubaki, are rejected under Art. 52.1 of the ICN. of them : 267, whCamellia : 139 becCamelliasect.Theopsis Cohen-Stuart in his Ph.D. thesis, which constituted an effective publication under Art. 30.9 of the ICN. Subsequently, he translated the first two chapters of his original thesis in Dutch into English and published it hort., C.euryoides Lindl., C.forrestii (Diels) Cohen-Stuart, C.henryana Cohen-Stuart, C.lutchuensis T. It\u00f4 ex T. It\u00f4 & Matsum., C.parvifolia (Hayata) Cohen-Stuart, C.punctata (Kochs) Cohen-Stuart and C.rosiflora Hook., in the key under sect. Theopsis. These nine species are presumably treated as the members of sect. Theopsis based on the structure of the key, the description of the section and the discussion. However, Theopsis. Theopsis were excluded and five of them, including C.euryoides, C.forrestii, C.lutchuensis, C.parvifolia, and C.rosiflora Nakai. Later, Theopsis as a synonym of Camellia and resumed sect. Theopsis . However, although Kochs\u2019s T.cuspidata was neither directly nor indirectly referenced in the protologue of C.cuspidata (T.cuspidata under Art. 41.4 (see Ex. 12) of the ICN.However, hronicle : 228. ThHenry 7026 were found at K and US, viz. K000380525 (the image is available at http://www.kew.org/herbcatimg/165067.jpg) and US 00504123 (the image is available at http://n2t.net/ark:/65665/308ec5722-d414-4a4d-b733-f34c3778997b). Since T.cuspidata based on Art. 40 Note 1. When A. Henry 7026 \u201d under C.cuspidata, the citation could be treated as the lectotypification of the species following Arts. 7.11, 9.10 & 9.19 of the ICN. Therefore, the lectotype of C.cuspidata is that of T.cuspidata, viz. Henry 7026 (K000380525), which, in turn, serves as the type of Theopsis (Table Furthermore, two duplicates of"} +{"text": "Archigetes Leuckart, 1878 is unique among all tapeworms in that its species can mature in invertebrate hosts (Oligochaeta), i.e., have a monoxenic (direct) life cycle. All five species were described as progenetic plerocercoids in oligochaetes and two of them also as adults from cypriniform fishes. Two species, A. sieboldi Leuckart, 1878 and A. iowensis Calentine, 1962, were found in North America in non-native common carp (Cyprinus carpio). A molecular study of caryophyllideans from the southern United States has revealed the occurrence of three new species in native freshwater fishes : Archigetes loculotruncatus n. sp. from Ictiobus bubalus, I. niger and Carpiodes cyprinus is the largest representative of the genus and differs by a loculotruncate scolex. Archigetes megacephalus n. sp. from Ictiobus niger, I. bubalus and I. cyprinellus is characterised by a prominent, bothrioloculodiscate scolex. Archigetes vadosus n. sp. from I. bubalus is typified by a globular scolex with very shallow loculi; it differs from the closely related A. sieboldi in the shape of the body, with a distinct neck region and a scolex wider than the remaining body. Archigetes iowensis Calentine, 1962 becomes a junior synonym of Paraglaridacris limnodrili . The generic diagnosis of Archigetes is amended and a key to identification of North American taxa is provided. Species of Archigetes and Paraglaridacris differ from each other most conspicuously in the structure of the ovary, which is follicular in Archigetes versus compact in Paraglaridacris.The caryophyllidean genus Archigetes Leuckart, 1878 are extraordinary among tapeworms due to their direct (monoxenic) life cycle, i.e., the lack of an intermediate host, with sexual maturation in the invertebrate host. Since its erection by Leuckart [The members of the genus Leuckart , the genLeuckart , 29. TheLeuckart , 11, 52.Archigetes recognised as valid [Archigetes species evolved by progenesis, i.e., early development of the reproductive system leading to sexual maturity (including the production of eggs) in a larval stage [This monoxenic cycle was found in all five species of the genus as valid , 19. Accas valid . An alteal stage . This scal stage , 42.Archigetes is neither the most basal lineage within all cestodes nor within the order Caryophyllidea [Archigetes species are members of the most recently diverging caryophyllidean lineage, which comprises almost entirely Nearctic caryophyllideans [Archigetes is a secondary abbreviation of the developmental cycle, similar to some spathebothriideans, such as Cyathocephalus truncatus , Diplocotyle olrikii Krabbe, 1874 or Spathebothrium simplex Linton, 1922, whose maturation and egg production may occur in gammarid amphipods as their intermediate host [Molecular data have clearly shown that hyllidea , 50. Thihyllidea . In contate host , 35, 46.Archigetes and the evolutionary origin of its monoxenic life cycle, there is much confusion about the species composition of the genus. Kennedy [A. sieboldi Leuckart, 1878 (type species); A. brachyurus Mr\u00e1zek, 1908; A. cryptobothrius Wisniewski, 1928; A. limnodrili Kennedy, 1965; and A. iowensis. However, no taxonomical revision based on properly fixed material and molecular data has been carried out. Moreover, the taxonomic position of some caryophyllideans placed in the genera Biacetabulum Hunter, 1927, Brachyurus Szidat, 1938 and Paraglaridacris Janiszewska, 1950 is also problematic, as they morphologically resemble the species of Archigetes.In addition to controversies over the position of Kennedy considerArchigetes was first reported from North America by Ward [Archigetes spp. known from Europe in a fish from the Illinois River at Havana. The genus was for a long time represented in North America by only two species, A. iowensis Calentine, 1962, described from non-native common carp (Cyprinus carpio L.) and Limnodrilus hoffmeisteri Clapar\u00e8de [A. sieboldi, reported from the same hosts [Archigetes tapeworms, which may represent putative new species, from eastern shiners, Notropis spp. (Cypriniformes: Leuciscidae), and silverside, Chirostoma humboldtianum (Atheriniformes: Atherinidae) in the Nearctic part of Mexico. The latter fish is the first representative of the order Atheriniformes that has been reported as the host of caryophyllidean tapeworms [The genus by Ward who founlapar\u00e8de , and A. me hosts . Recentlme hosts reportedapeworms .Biacetabulum Hunter, 1927, Promonobothrium Mackiewicz, 1968 and Isoglaridacris Mackiewicz, 1965 described [Archigetes are described from catostomid fishes from the southern United States (USA). In addition, species diversity of the genus is discussed together with the assessment of their phylogenetic relationships. The diagnosis of Archigetes is amended and a key to identification of North American taxa, including A. iowensis transferred to Paraglaridacris, is provided. Taxonomic status of morphologically similar species of the latter genus, which may also mature in oligochaetes, is discussed based on material from North America (USA), Asia (Japan) and Europe .Recent studies on North American caryophyllideans have revealed high diversity of these tapeworms, previously only partly described. Two new genera were erected and nine new species of the genera escribed , 54\u201356. The specimens studied were newly collected by the present authors and their collaborators in Mississippi (USA), in 2012 and 2019. In addition, specimens from the private collection of the late John S. Mackiewicz (USA) donated to the senior author (T.S.) and vouchers deposited in the Helminthological Collection of the Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, \u010cesk\u00e9 Bud\u011bjovice (IPCAS) were examined.Newly collected tapeworms were obtained from the intestines of freshly killed fish; they were rinsed with saline and fixed in hot, nearly boiling, 4% formaldehyde for morphological studies . Some wolsrDNA) sequences. A list of sequenced samples and sequences used in the phylogenetic analysis is provided in lsrDNA sequences were aligned with the sequences of Archigetes spp. and Biacetabulum spp. available in GenBank using ClustalW implemented in Geneious ver. 11 . The length of the final alignment was 1329 nucleotides (nt).The phylogenetic relationships of the studied tapeworms were assessed based on the partial D1\u2013D3 region) nuclear ribosomal large subunit rRNA gene ( region np-distance), a separate alignment including only sequences of Archigetes spp. (1356 nt) was used in MEGA ver. X [Bayesian inference (BI) and maximum likelihood (ML) methods were used to assess phylogenetic relationships within the dataset. The best-fitting model for the analyses, GTR\u00a0+\u00a0I\u00a0+\u00a0G, was estimated using jModelTest 2.1.2 . MrBayesA ver. X .In addition to IPCAS (see above), the studied specimens are deposited in the National Helminthological Collection of Mexico, Instituto de Biolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico (CNHE), Harold W. Manter Laboratory, University of Nebraska, Lincoln, USA (HWML), and the National Museum of Natural History, Washington, D.C., USA (USNM). The terminology of the scolex morphology follows the proposal of Mackiewicz and OrosHost code numbers correspond to a unique individual fish host examined and small letters specify individual tapeworm(s) found in this host, i.e., correspond to morphological voucher(s). See Archigetes and sequences of this genus available in GenBank, revealed a well-supported monophyletic group . In contrast to conspicuous morphological differences (see below), the interspecific divergence between A. sieboldi and this new species was rather low and ranged between 1 and 5 nt (0.08\u20130.37%). Clades II and III contained isolates representing two species from Ictiobus spp. in North America that were recognised as species new to science. Sequences of Clade II were identical. The three new species are described below. The nucleotide divergence of sequences of each isolate is summarised in Supplementary Table S1.Molecular phylogenetic analysis, which included sequences of nine newly recovered isolates of ic group . ArchigeArchigetes, but only the four following species were recently recognised as valid [A. sieboldi Leuckart, 1878 (type species); A. brachyurus Mr\u00e1zek, 1908 ; and A. iowensis (species reported from oligochaetes and fish). Scholz and Oros [Paraglaridacris limnodrili Mackiewicz, 1994 also among valid species of Archigetes. The validity of two species, namely A. brachyurus and A. cryptobothrius, which have been reported only from Europe [Several taxa have been placed in as valid : A. sieband fish ); A. cryand Oros erroneoum Europe , could nArchigetes sieboldi and A. iowensis also occur in North America and their taxonomic status and biogeography are briefly discussed below. In addition to the three unidentified morphotypes of Archigetes recently reported from Mexico [m Mexico , anotherArchigetes sp. 1 of Scholz et al. [Syn.: z et al. urn:lsid:zoobank.org:act:1C1DE51D-7DC2-41A6-9CCB-9AC1BC31089FType host: Ictiobus bubalus (Rafinesque), Smallmouth buffalo.Other host: Ictiobus niger (Rafinesque), Black buffalo; Carpiodes cyprinus (Lesueur), Quillback .Site in host: Anterior intestine.Type locality: Chotard Lake near Vicksburg, Mississippi, USA .Additional localities: Pascagoula River, Benndale; Sunflower River, Indianola ; Reelfoot Lake, Tennessee, USA.Type material: Holotype from I. bubalus (host code No. US 260d) collected on 24 March 2012 (IPCAS C-903/1); three paratypes from I. bubalus (IPCAS C-903/1); four paratypes from I. niger (US 244b) ; two paratypes from I. bubalus (US 257a) (USNM 1661733).Material studied: Four slides with eight whole-mounted specimens and five slides with sagittal and cross sections of another specimen from I. bubalus (US 257a and 260b \u2013 PBI464); five slides with nine specimens (one incomplete) and five slides with longitudinal and cross sections of another specimen from I. niger (US 244b); one slide with one whole-mounted specimen from C. cyprinus (host code No. US 262b), all specimens from Chotard Lake near Vicksburg, collected by the authors (R.K. and M.O.) on 23 and 24 March 2012; one slide with whole-mounted specimen from C. cyprinus (host code No. US 171a) from Pascagoula River, near Benndale, coll. by the same authors on 18 March 2012; one slide with whole-mounted specimen from\u00a0I. bubalus\u00a0(host code No. RF3/490), Reelfoot Lake, donated by J.S. Mackiewicz to T.S.; two slides with two immature specimens from I. niger (FR19_765), Sunflower River coll. by F. Reyda on 17 August 2019.Representative DNA sequences and phylogenetic relationships: Sequences of one individual from I. bubalus (US 260d/PBI-464) in Mississippi were provided by Scholz et al. [ssr DNA (GenBank Accession Nos. MW027441), lsr DNA (MW027502) and rrnL (MW027379); Scholz et al. [lsrDNA sequences by 16\u201320 nt (1.18\u20131.48%) (Supplementary Table S1).z et al. : ssr DNADNA MW0272 and rrnEtymology: The species name loculotruncatus refers to the loculotruncate scolex, which is a unique characteristic of this new species among other members of the genus Archigetes.Description , wider Testes medullary, subspherical to widely oval ; 5D. AntOvary butterfly-shaped, with follicular lateral wings , 3C. Vagin utero.Uterus forms several loops, with single loop extending slightly anterior to cirrus-sac , 3C; utevs 1.1\u20133.5\u00a0mm in the other five valid species. It also differs from all valid species of Archigetes, including the other two new species described below, in possessing a loculotruncate an elongate seminal vesicle, which is longer than the diameter of the cirrus-sac in the new species vs spherical and smaller than the cirrus-sac in the other valid species.The new species is also distinguished from the five previously known species by (i) a relatively long neck, whose length represents 10\u201315% of the total body length and which is absent or indistinct in the other species; (ii) a butterfly-shaped ovary in the new species Archigetes based on morphological and molecular data , but diArchigetes sp. 2 of Scholz et al. [Syn.: z et al. urn:lsid:zoobank.org:act:66185BB1-AF2D-456C-BA5E-7A83385207CEType host: Ictiobus niger (Rafinesque), Black buffalo.Other host: Ictiobus bubalus (Rafinesque), Smallmouth buffalo; Ictiobus cyprinellus , Bigmouth buffalo .Site in host: Anterior intestine.Type locality: Chotard Lake near Vicksburg, Mississippi, USA .Additional localities: Pascagoula River, Wilkerson\u2019s Ferry launch , Reelfoot Lake, Tennessee, USA.Type material: Holotype from I. niger collected on 23 March 2012 (host code No. US 244b) (IPCAS C-904/3); two paratypes from I. niger (US 244b) ; seven paratypes from I. cyprinellus (US 242a) ; one paratype from I. bubalus (IPCAS C-904/2).Material studied: One slide with one whole-mounted specimen from I. bubalus (US 257b), collected by the present authors (R.K. and M.O.) on 24 March 2012; two slides with two specimens from I. bubalus (DNA-02-267D), coll. by R.M. Overstreet and S.S. Curran in 2002; five slides with eight whole-mounted specimens and one slide with longitudinal sections of another specimen from I. cyprinellus (host code No. US 242a \u2013 PBI-462); three slides with four specimens from I. niger (US 244b \u2013 PBI-417), coll. authors (R.K. and M.O.) on 23 March 2012; all specimens from Chotard Lake near Vicksburg;\u00a0two slides with five whole-mounted specimens from I. bubalus (host code No. RF3/490), Reelfoot Lake, donated by J.S. Mackiewicz to T.S.Representative DNA sequences and phylogenetic relationships: The lsrDNA sequences of one individual from I. bubalus (US 260b \u2013 OM103265), one from I. cyprinellus (US 242a/PBI-462 \u2013 MW027493), and three from I. niger , all from Chotard Lake. Three novel sequences and two sequences retrieved from GenBank were identical. They differed from the sequence of Archigetes loculotruncatus n. sp. by 16 nt (1.18%) (Supplementary Table S1).Etymology: The species name, mega \u2013 very big; cephalus \u2013 head or scolex, refers to a conspicuously large scolex, the width of which considerably exceeds that of the neck.Description . Body ez et al. ), spheriTestes medullary, subspherical to widely oval . AnterioOvary butterfly-shaped, follicular , 8C. VagPreovarian vitelline follicles numerous, in medullary parenchyma ; 8A, almin utero.Uterus forms several loops, one loop extending slightly anterior to cirrus-sac , 8C; uteArchigetes loculotruncatus n. sp., by the shape and relative size of the scolex, which is bothrioloculodiscate and conspicuously (>\u00a02\u00d7) wider than the body examined from Chotard Lake (western part of Mississippi State), and in smallmouth buffalo from Reelfoot Lake, Tennessee. The new species was found sympatric with A. loculotruncatus n. sp. in the anterior part of the intestine in three fish individuals, one black buffalo (US 244) and two smallmouth buffalo . These new species can be distinguished from each other mainly by the shape and size of the scolex and body length, but live cestodes are highly mobile and change shape, including the scolex. For this reason, identification of live specimens with the naked eye can be difficult in mixed infections. Specimens should be fixed with hot fixative so that they retain their natural shape and do not shrink unnaturally, as is typical for specimens fixed with unheated fixative.urn:lsid:zoobank.org:act:21724C2F-6202-4E5D-A514-D9D832598A12Type host: Ictiobus bubalus (Rafinesque), Smallmouth buffalo .Site in host: Anterior intestine.Type locality: Bluff Creek, Mississippi, USA .Additional localities: Pascagoula River and Sunflower River, Indianola , Reelfoot Lake .Type material: Holotype from I. bubalus (host code No. US 862d) collected on 23 June 2019 (IPCAS C-905/1); two paratypes (hologenophores) from I. bubalus (IPCAS C-905/1); one paratype from I. bubalus (US 831d-3), one paratype from I. bubalus (US 863c) (USNM 1661736); two paratypes from I. bubalus (US 869b) ; one paratype from I. bubalus (US 871a) (USNM 1661737).Material studied: Fifteen slides with 16 whole-mounted specimens from I. bubalus from Oxbow south of Cumbest Bridge landing on the Pascagoula River and Bluff Creek, collected by the present authors on 19 and 23 June 2019; one slide with two whole-mounted specimens from I. bubalus (FR19_655), Oxbow on the Pascagoula River, Vancleave, coll. by F. Reyda on 12 August 2019; two slides with two whole-mounted specimens (one slide together with A. iowensis \u2013 see below) from I. bubalus (FR19_767) from Sunflower River, coll. by F. Reyda on 17 August 2019; four slides with eight whole-mounted specimens from\u00a0I. bubalus\u00a0(host code No. RF3/490), Reelfoot Lake, donated by J.S. Mackiewicz to T.S.Representative DNA sequences and phylogenetic relationships: The lsrDNA sequences of six individuals from I. bubalus . Sequence divergence among individual isolates of A. vadosus n. sp. was 0\u20134 nt (0\u20130.30%). They differed from sequence of A. loculotruncatus n. sp. by 17\u201320 nt (1.33\u20131.41%), from sequences of A. megacephalus n. sp. by 4\u20135 nt (0.30\u20130.37%), and from sequences of A. sieboldi by 1\u20135 nt (0.08\u20130.37%).Etymology: The species name vadosus refers to the unusually shallow pair of median loculi.Description . Body eTestes medullary, subspherical to widely oval . AnterioOvary butterfly-shaped, follicular . Vagina in utero.Uterus forms several loops, one loop extending anterior to cirrus-sac ; uterineArchigetes by having an elongate body with a distinct neck, and from the two new species by possessing a bulboloculate scolex with shallow median loculi, almost indistinct lateral loculi and indistinct apical disc . Other biometrical differences from A. loculotruncatus n. sp. and A. megacephalus n. sp. are obvious in A. sieboldi Kennedy, 1965; Archigetes iowensis Calentine, 1962 (new synonym)Syns.: Type host: Cyprinus carpio Linnaeus, Common carp (Cypriniformes: Cyprinidae).Other hosts: Ictiobus bubalus (Rafinesque), Smallmouth buffalo (new host record); Limnodrilus hoffmeisteri Clapar\u00e8de, Red worm (Clitellata: Naididae) (progenetic plerocercoids).Site in host: Anterior intestine (fish) and body cavity (naidids).Type locality: Iowa River, Hardin County, Iowa, USA.Distribution: Whole USA .Type specimens: Holotype from C. carpio (USNM 1355440); paratype from L. hoffmeisteri (USNM 1355441).Material studied: One specimen from the intestine of I. bubalus , Sunflower River, Indianola, Mississippi, collected by F. Reyda on 17 August 2019; one specimen from the body cavity of L. hoffmeisteri, locality unspecified, donated by J.S. Mackiewicz to T.S. (IPCAS C-588/1); four whole-mounted specimens and two slides with longitudinal sections of another specimen from Cyprinus carpio (BN C-78), Wisconsin, USA, coll. by R.L. Calentine in 1966 and donated by J.S. Mackiewicz to T.S. (IPCAS C-588/2).Representative DNA sequences: Not available.Redescription . Body nz et al. ), slightTestes medullary, subspherical to widely oval , with fiOvary compact (non-follicular), dumb-bell-shaped . Vagina in utero.Uterus forms several loops, with distal part of uterus not extending farther anteriorly than cirrus-sac . UterineA. iowensis based on adults found in common carp and progenetic plerocercoids in the naidid L. hoffmeisteri from the Iowa River. The same author [A. iowensis in L. hoffmeisteri in Wisconsin , but designated his specimens as \u201cArchigetes limnocesti\u201d, which is a non-existing name (nomen nudum).Calentine describee author studied e author also fouA. iowensis from cypriniforms and oligochaete host with those of Paraglaridacris limnodrili from the Palearctic region has revealed that these species can be distinguished from each other neither by their morphology nor measurements [Comparison of North American specimens of urements , 43, 61.Archigetes iowensis and P. limnodrili have been found as adults in cypriniforms and as progenetic plerocercoids in oligochaetes [A. iowensis becomes a junior synonym of P. limnodrili and the number of valid species of Archigetes is reduced to six .Both species are typified by (i) a compact, dumb-bell-shaped ovary; (ii) a small body separated by a short, but distinct neck, which is slightly narrower than the scolex, anterior-most testes being always anterior to anterior-most vitelline follicles; (iii) largely lateral preovarian vitelline follicles, with a very few median folllicles .Other hosts ; shortfin silverside, Chirostoma humboldtianum (Atheriniformes: Atherinidae) (new host record).a et al. ): CommonSite in host: Body cavity (progenetic plerocercoids in oligochaetes); intestine (adults in fish).Type locality: Ponds and puddles around Leipzig, Germany.Distribution: Kinnickinnic River, River Falls, Wisconsin, USA [sin, USA ; Lago desin, USA .Morphological description: Mr\u00e1zek [: Mr\u00e1zek , Kennedy: Mr\u00e1zek , Calenti: Mr\u00e1zek , Protaso: Mr\u00e1zek .Material studied: seven plerocercoids from L. hoffmeisteri\u00a0and\u00a0L. udekemianus Clapar\u00e8de; two adults from\u00a0C. carpio, both from several fishponds in South Bohemia, Czech Republic, collected by F. Moravec and T.S. between 1984 and 1988 [C. carpio, Tisa River near Velk\u00e9 Trakany, Slovakia, coll. by M.O. and V. Hanzelov\u00e1 in June 2006 and 2007, and April 2008 ; one adult from\u00a0Blicca bjoerkna (L.),\u00a0Latorica River, Slovakia, coll. by R. Ergens in 1964 (IPCAS C-45/3); two adults from\u00a0Abramis brama (L.), two fishponds in Pr\u016fhonice park near Prague and \u010cesk\u00e9 Bud\u011bjovice, respectively, coll. by T.S. in 1983 and 1990 (IPCAS C-45/4); two adults from\u00a0Pseudorasbora parva (Temminck & Schlegel), and two adults from\u00a0Rhynchocypris lagowskii (Dybowski), Lake Suwa, Japan, coll. by T. Shimazu in 1992 ; six adults from\u00a0Gnathopogon elongatus (Temminck & Schlegel), Kawashima, Japan, coll. by M. Urabe in 2002, 2003 and 2012 (IPCAS C-45/7); six plerocercoids from\u00a0Limnodrilus udekemianus, Latka River near Borok, Yaroslavl Region, Russia, coll. by L.G. Poddubnaya in 2000 (IPCAS C-368/1); one specimen from Chirostoma humboldtianum, Lago de Zacapu, Michoac\u00e1n, collected by Berenit Mendoza-Garfias in November 2008 ; 13 adul de Le\u00f3n ).Representative DNA sequences and phylogenetic relationships: Olson et al. [A. sieboldi from the fish host Gnathopogon elongatus in Japan and progenetic plerocercoid from the coelom of oligochaete L. hoffmeisteri in Russia: EU343744, EU343745 and EU343736 (lsrDNA). Scholz et al. [A. sieboldi from gudgeon, Gobio gobio L. (Cyprinidae) from the Czech Republic: MW027431 (ssr DNA) and MW027492 (lsr DNA). The lsr DNA sequences of this species from both studies differed by 3 nt (0.24%).n et al. sequencez et al. sequenceA. sieboldi from the Kinnickinnic River in Wisconsin. The authors concluded that gravid stages occur in oligochaetes and occasionally in fish because a high prevalence of infection with A. sieboldi in oligochaetes compared to its rare occurrence in fish indicates that A. sieboldi is primarily a parasite of oligochaetes. Wi\u015bniewski [Tinca tinca (L.)) with A. sieboldi from oligochaetes.Calentine and DeLong and Cale\u015bniewski and Nybe\u015bniewski in Europ\u015bniewski successfChirostoma humboldtianum in Mexico, designated as Archigetes sp. 3 by Scholz and P\u00e9rez-Ponce de Le\u00f3n [A. sieboldi found by Calentine and DeLong [A. sieboldi from C. humboldtianum in Mexico and represents a new definitive host and new geographical area, but this fish species should be confirmed as a true host of A. sieboldi.The specimen from de Le\u00f3n , dumb-bell-shaped ovary, uterine loops reaching far anterior to the cirrus-sac, and the external seminal vesicle smaller than the cirrus-sac.Scholz and P\u00e9rez-Ponce de Le\u00f3n reportedParaglaridacris limnodrili (syn. A. iowensis) by the lateral and median position of preovarian vitelline follicles , and by much shallower loculi on the scolex in Mexican specimens . The third morphotype from C. humboldtianum (Archigetes sp. 3) resembles in its morphology A. sieboldi found by Calentine and DeLong [All the three morphotypes can be distinguished from d DeLong in NorthArchigetes sp. in creek chub, Semotilus atromaculatus Mitchill (Cypriniformes: Leuciscidae), Sugar Creek, Normal, Illinois, USA. Voucher specimens were not available to the present authors.Camp found twA. brachyurus and A. cryptobothrius, the identification key includes only five species of both morphologically similar genera that occur in North America. Morphotypes Archigetes sp. 1 and sp. 2 from Mexico are not included (see above).P. limnodrili (synonym A. iowensis)1a. Ovary compact; anterior-most testes anterior to anterior-most vitelline follicles; median vitelline follicles almost completely absent ........................................................................................................................... 1b. Ovary follicular; anterior-most testes posterior to anterior-most vitelline follicles; median vitelline follicles present ...... 22a. Ovary butterfly-shaped; neck distinct, narrower than the body .............................................................................. 3A. sieboldi2b. Ovary dumb-bell-shaped; neck indistinct, wider than the scolex ............................................................ 3a. Body short (length\u00a0<\u00a05\u00a0mm), scolex bothrioloculodiscate or bulboloculate .............................................................. 4A. loculotruncatus n. sp.3b. Body long (length\u00a0>\u00a05\u00a0mm), scolex loculotruncate ........................................................... A.\u00a0megacephalus n. sp.4a. Scolex bothrioloculodiscate, conspicuously (> 2\u00d7) wider than the body .............................. A. vadosus n. sp.4b. Scolex bulboloculate, only slightly wider than the body ............................................................... Because of the lack of newly collected or museum material of Archigetes have been reported in North America [Archigetes species that now include also catostomids (suckers). Three new species were found in the southern part of the USA, whereas Paraglaridacris limnodrili (new syn. A. iowensis) and A. sieboldi were previously known only from the Midwest (Iowa and Wisconsin). The present study, together with previous studies by the present authors, clearly demonstrates that the Nearctic fauna of freshwater fish tapeworms is still severely underexplored and insufficiently known [Previously, only two nominal taxa of America \u20137, 58. Nly known , 47.Archigetes have an elongate body with a distinct, relatively long neck , butterfly-shaped ovary, and a conical to globular scolex wider than the neck. The new species also share the presence of a small, shallow genital atrium to which the male and female gonopores open separately, thus not forming a single hermaphroditic duct. The presence of a single common gonopore or two separate gonopores has been considered taxonomically important at the genus-level. Mackiewicz [All new North American species of ckiewicz distinguArchigetes and the closely related genus Biacetabulum Hunter, 1927 should have a single gonopore according to Mackiewicz [Biacetabulum spp. have shown that the male and female gonopores are separate and do not form a hermaphroditic duct, but open into a shallow genital atrium . Th. ThArchiium in Australia. The authors placed the species in\u00a0Biacetabulum\u00a0because of the anterior extent of the uterus far anterior to the cirrus-sac and the presence of two acetabulum-like loculi on the scolex. Scholz and Oros [B. tandani\u00a0is provisionally retained in\u00a0Biacetabulum\u00a0until new material is available. The most intriguing features of this poorly known species are its occurrence in a very distant zoogeographical distribution from that of species of both genera, which occur in the Palaearctic and Nearctic zoogeographical regions, and the presence of an external seminal vesicle, which is a morphological characteristic present only in most species of the Capingentidae, including\u00a0Archigetes\u00a0and\u00a0Biacetabulum\u00a0, different spectrum of fish hosts (Catostomidae versus\u00a0Cyprinidae) and partly zoogeographical distribution . Comparison of sequence data from A. sieboldi from North America with A. vadosus could be quite instructive, but no ethanol-fixed material of A. sieboldi from North America is available. Another obstacle to better understand relationships between caryophyllidean tapeworms is the existence of multiple mt haplotypes that most likely represent paralogs (i.e. numts), which were detected by Brabec et al. [cox1 and nad3).One of the interesting results of molecular analysis is that both European isolates of c et al. in two mArchigetes form a monophyletic group nested within the clade composed of Biacetabulum spp. ) in Archigetes and Biacetabulum [Biacetabulum and differentiated them only by exclusive egg production of progenetic plerocercoids in oligochaetes for species of Archigetes versus full maturation exclusively in teleosts for species of Biacetabulum.The close relationship between the species of etabulum . Hunter etabulum mentioneArchigetes has priority and all species of Biacetabulum would be transferred to this genus, provided that both genera are considered synonymous. Unfortunately, no molecular data are available for the type species of B. infrequens Hunter, 1927. Therefore, the synonymy of the two genera is not yet proposed. However, these two genera could be distinguished from each other by a somewhat smaller body in Archigetes , an H-shaped ovary in Biacetabulum vs dumb-bell-shaped ovary in Archigetes, the extent of vitelline follicles, which may be present alongside the ovary in Archigetes but are absent in Biacetabulum, and uterine loops extending slightly anterior to the cirrus-sac in Archigetes vs uterine loops extending far anterior to the cirrus-sac in Biacetabulum. The addition of three new species with a larger body and a butterfly-shaped ovary implies that the generic diagnosis of the genus should be amended:Based on the ICZN priorityAmended generic diagnosis: Caryophyllidea: Capingentidae sensu Scholz et al. [in utero. Parasites of cyprinids (Cyprinidae) and catostomids in Holarctic Region. Progenetic plerocercoids in coelom of naidid oligochaetes.z et al. . Body smType species: Archigetes sieboldi Leuckart, 1878.Additional species: Archigetes brachyurus Mr\u00e1zek, 1908; Archigetes cryptobothrius Wi\u015bniewski, 1928; Archigetes loculotruncatus n. sp.; Archigetes megacephalus n. sp.; Archigetes vadosus n. sp.Archigetes is still insufficiently clear because European taxa were described superficially, without any type or voucher specimens deposited in collections. Archigetes brachyurus and A. cryptobothrius were described in the first third of the 20th century from oligochaetes L. hoffmeisteri from the Czech Republic and Poland, respectively [A. brachyurus having a hexagonal scolex with deep loculi and a distinct, narrow neck , whereaA. brachyurus, versus 154 in several rows of 18\u201326 each, in A. cryptobothrius. In addition, this differential criterion is questionable because of difficulties in reliably counting numerous testes and their aggregation in rows. Nevertheless, both species are considered valid by most authors [A. brachyurus, namely Abramis brama (L.), Barbus barbus (L.), Barbus petenyi Heckel,\u00a0Gobio gobio, and\u00a0Vimba vimba\u00a0(L.). However, no details on geographical origin and morphology of these specimens were provided. Protasova et al. [L. hoffmeisteri but these larvae identified as A. brachyurus differ from each other considerably in the shape of the body and scolex, and in the number of testes. Archigetes cryptobothrius has been reported only once since its original description, in L. hoffmeisteri from the Susaa River at\u00a0M\u00f8llebro and Nym\u00f8llebro in Denmark [Kennedy differen authors , 43, 48.Paraglaridacris Janiszewska, 1950 as the first available name for Brachyurus Szidat, 1938, which was preoccupied by Brachyurus Fischer-Waldheim, 1813 (a genus of rodents). Szidat [Brachyurus, apparently unaware that this generic name was preoccupied, to accommodate B. gobii Szidat, 1938, which he found in G. gobio from small fishpond around the former Prussian town of Rossitten in Curonian Spit. Kennedy [Glaridacris limnodrili as A. limnodrili. Mackiewicz [G. limnodrili to belong to Brachyurus Szidat, 1938, nec Fischer-Waldheim, 1813 . Comparison of A. iowensis specimens with Paraglaridacris limnodrili did not reveal any difference in their morphology and measurements in the present study compact ovary (versus follicular in Archigetes); (ii) largely lateral preovarian vitelline follicles, with only very few follicles median (median follicles are common in Archigetes); (iii) more anterior position of the first testes compared to vitelline follicles . The difference in the structure of the ovary is conspicuous and enables easy differentiation between the specimens of both genera. Therefore, Paraglaridacris is provisionally considered a valid genus. It should also be mentioned here that two of the present authors contributed to the existing confusion as to nomenclature of these tapeworms [The validity of apeworms .Archigetes and P. limnodrili was previously considered narrow, especially in North America. Calentine [L. hoffmeisteri was infected, with the same results of experimental infections of oligochaetes. A similarly narrow host range was reported for A. sieboldi in North America [Chirostoma humboldtianum from Mexico by Scholz and P\u00e9rez-Ponce de Le\u00f3n [A. iowensis in smallmouth buffalo, i.e., fish of a different family (Catostomidae), also challenges the above-mentioned assumption about strict host specificity of these species at the level of fish definitive host. Indeed, a broader host spectrum has been reported for A. sieboldi and P. limnodrili in the Palaearctic region is given above diagonal and the number of variable nucleotides below diagonal."} +{"text": "Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time.In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3\u20134\u200ayears to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes.This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways. N-glycans at the gp120-gp41 interface as previously described . The number of donors in the SPARTAC cohort that developed bnAbs was too small to find any meaningful differences between HIV-1 subtype and bnAb epitope. When comparing the kinetics of bnAb development with the specificity of the bnAb response, we see that for the donors that target the V3/N332 and N160/V2 epitopes, induction of heterologous neutralization coincides with bnAbs targeting the glycan epitopes. The bnAb responses then broaden incrementally over time as the infection proceeds. This trend in bnAb development was previously seen in donors PC76 from IAVI protocol C and CAP1Although CD4-binding site Abs were common in the SPARTAC cohort , the development of CD4-binding site bnAbs was rare. In the IAVI Protocol C cohort, CD4-binding site Abs took longer to develop than the N332/V3 and N160/V2 bnAbs, presumably because of the very high level of somatic hypermutation required for neutralization breadth . Indeed,In conclusion, we show that in the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads. We identify individuals for which more in-depth studies on antibody--viral co-evolution will be conducted to better understand how bnAbs arise during natural infection at the molecular level.We thank Carl Graham for helpful discussions and critical reading of the manuscript. We thank Dr Christine Mant and Dr John Cason of the King's College London Infectious Diseases Biobank for providing plasma samples. We thank all the participants and staff at all the sites participating in the SPARTAC trial. The SPARTAC Trial Investigators: Trial Steering Committee: Independent Members \u2013 A. Breckenridge (Chair), P. Clayden, C. Conlon, F. Conradie, J. Kaldor\u2217, F. Maggiolo, F. Ssali, Country Principal Investigators- D.A. Cooper, P. Kaleebu, G. Ramjee, M. Schechter, G. Tambussi, J.M. Miro, J. Weber. Trial Physician: S. Fidler. Trial Statistician: A. Babiker. Data and Safety Monitoring Committee (DSMC): T. Peto (Chair), A. McLaren (in memoriam), V. Beral, G. Chene, J. Hakim. Co-ordinating Trial Centre: Medical Research Council Clinical Trials Unit, London . Central Immunology Laboratories and Repositories: The Peter Medawar Building for Pathogen Research, University of Oxford, UK . Central Virology Laboratories and Repositories: Jefferiss Trust Laboratories, Imperial College, London, UK . Clinical Endpoint Review Committee: N. Paton, S. Fidler. Investigators and Staff at Participating Sites: Australia: St Vincents Hospital, Sydney (A. Kelleher), Northside Clinic, Melbourne (R. Moore), East Sydney Doctors, Sydney (R. McFarlane), Prahran Market Clinic, Melbourne (N. Roth), Taylor Square Private Clinic, Sydney (R. Finlayson), The Centre Clinic, Melbourne (B. Kiem Tee), Sexual Health Centre, Melbourne (T. Read), AIDS Medical Unit, Brisbane (M. Kelly), Burwood Rd Practice, Sydney (N. Doong), Holdsworth House Medical Practice, Sydney (M. Bloch), Aids Research Initiative, Sydney (C. Workman). Coordinating Centre in Australia: Kirby Institute University of New South Wales, Sydney . Brazil: Projeto Praca Onze, Hospital Escola Sao Francisco de Assis, Universidade federal do Rio de Janeiro, Rio de Janeiro . Italy: Ospedale San Raffaele, Milan , Ospedale Lazzaro Spallanzani, Roma . South Africa: Cape Town: Desmond Tutu HIV-1 Centre, Institute of Infectious Diseases, Cape Town . Johannesburg: The Wits Reproductive Health and HIV-1 Institute, University of Witswatersrand, Hillbrow Health Precinct, Johannesburg , Contract Laboratory Services, Johannesburg Hospital, Johannesburg . Kwazulu-Natal: HIV-1 Prevention Unit, Medical Research Council, Durban . Uganda: Medical Research Council/Uganda Virus Research Institute, Entebbe . Spain: Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona . UK and Ireland: Royal Sussex County Hospital, Brighton , St James's Hospital, Dublin , Regional Infectious Diseases Unit, Western General Hospital and Genitourinary Dept, Royal Infirmary of Edinburgh, Edinburgh , Chelsea and Westminster Hospital, London , Homerton Hospital, London , Mortimer Market Centre, London , North Middlesex Hospital , Royal Free Hospital, London , Barts & the London NHS Trust, London , St Marys Hospital, London , Birmingham Heartlands Hospital, Birmingham . Imperial College Trial Secretariat: S. Keeling, A. Becker. Imperial College DSMC Secretariat: C. Boocock.(Asterisk (\u2217) indicates that the members left the study team before the trial ended.)Author contributions: K.J.D., J.F., L.A.G., I.H. designed the study. L.A.G., I.H. and F.D. performed experiments. K.J.D., L.A.G. and I.H. conducted data analysis. P.K., M.S., G.T., J.W., J.M.M., R.P., A.B., D.A.C., M.F., G.R., S.F., J.F., J.F. and SPARTAC Investigators set up the SPARTAC cohort. K.J.D., J.F., I.H. and L.A.G. wrote the manuscript with input from the remaining authors.Funding: This project has received funding from Wellcome (069598/Z/02/Z), European Union's Horizon 2020 Research and Innovation program under grant agreement no. 681137 (to K.J.D. and I.H.), the Medical Research Council (MRC) (to K.J.D. [MR/K024426/1]), the, Rosetrees Trust and Fondation Dormeur, Vaduz (to\u200aK.J.D). This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas\u2019 NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. L.A.G. were supported by the King's Bioscience Institute and the Guy's and St Thomas\u2019 Charity Prize Ph.D. Programme in Biomedical and Translational Science. J.M.M. received a personal 80\u200a:\u200a20 research grant from Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017\u20132021.There are no conflicts of interest."} +{"text": "Nature Communications 10.1038/s41467-021-27030-z, published online 22 November 2021.Correction to: J. Clim. 26, 9880\u20139902 (2013).The original version of this Article contained an error in ref. 5, which was incorrectly given with the wrong first author name as: Carmago, S. J. The correct form of ref. 5 is: Camargo, S. J. Global and regional aspects of tropical cyclone activity in the CMIP5 models. This has been corrected in the PDF and HTML versions of the Article."} +{"text": "Anaplasma spp. and Ehrlichia chaffeensis in livestock in Qinghai. A total of 566 blood samples, including 330 yaks (Bos grunniens) and 236 Tibetan sheep (Ovis aries) were screened. Results showed that A. bovis and A. phagocytophilum were most prevalent in yaks, followed by A. ovis , A. capra , and E. chaffeensis . While A. ovis and A. bovis infection was identified in Tibetan sheep. To our knowledge, it is the first time that A. capra and E. chaffeensis have been detected in yaks in China. Apart from that, we also found that co-infection of A. bovis and A. phagocytophilum is common in yaks . For triple co-infection, two yaks were infected with A. bovis, A. phagocytophilum, and A. capra, and two yaks were infected with A. bovis, A. phagocytophilum, and E. chaffeensis. Risk analysis shows that infection with A. bovis, A. phagocytophilum, and A. ovis was related to region and altitude. This study provides new data on the prevalence of Anaplasma spp. and E. chaffeensis in Qinghai, China, which may help to develop new strategies for active responding to these pathogens.Tick-borne diseases (TBDs) can cause serious economic losses and are very important to animal and public health. To date, research on TBDs has been limited in Qinghai-Tibet Plateau, China. This epidemiological investigation was conducted to evaluate the distribution and risk factors of Anaplasma species have been identified, including A. bovis, A. phagocytophilum, A. centrale, A. platys, A. marginale, A. ovis, and A. capra , tick-borne fever in ruminants, and canine and equine granulocytic anaplasmosis , and ehris (HME) .Anaplasma and Ehrlichia infections are very common in many countries and yaks (Bos grunniens) are the main domestic animals in Qinghai and an important source of life and income for herders. Ixodid tick infestation in livestock is a common and severe problem, and more than 25 tick species in six genera have been reported in Qinghai and Tibetan sheep (n = 236) were collected using random sampling from six sampling sites in Maqin , Dari , and Banma of Guoluo Tibetan Autonomous Prefecture (GL), and Yushu , Zhiduo and Qumalai of Yushu Tibetan Autonomous Prefecture (YS) during June 2020 in Qinghai, China . The concentration of the extracted DNA was detected by NanoDrop 2,000 and then stored at \u221220\u00b0C for pathogens detection.Anaplasma spp. and E. chaffeensis in extracted DNA. Nested PCRs were employed to detect A. bovis, A. phagocytophilum, A. centrale, A. platys, and E. chaffeensis based on 16S rRNA gene. Conventional PCR based on the msp4 genes was employed to detect A. marginale and A. ovis, while 16S rRNA gene for detection of A. capra. PCR primers and cycling conditions used in this study, as shown in A. bovis, A. phagocytophilum, A. ovis, A. capra, and E. chaffeensis that had been verified by sequencing, were used as a positive control for corresponding PCR reactions; double-distilled water was used as a negative control. The PCR products were detected by 1.5% agarose gel electrophoresis with M5 Hipure Next III Gelred stained.Conventional PCR or nested PCR was used to screen for Anaplasma spp. and E. chaffeensis randomly selected from each sampling site were sequenced by BGI . The sequence obtained by BGI sequencing was submitted to NCBI for BLASTn search (https://blast.ncbi.nlm.nih.gov/Blast.cgi), and sequence alignment and analysis. The representative nucleotide sequences of this study have been deposited in the GenBank database. Phylogenetic trees were constructed using the neighbor-joining method executed with the p-distance model in MEGA X. Bootstrap values were assessed with 1,000 bootstrap replicates in yaks. For co-infection with three pathogens, the infection rate of A. bovis, A. phagocytophilum, and A. capra was 0.6% (2/330), and the infection rate of A. bovis, A. phagocytophilum, and E. chaffeensis was 0.6% (2/330) (This study identified four and yaks . Of the (2/330) . No co-i16S rRNA gene sequences of A. bovis, A. phagocytophilum, A. capra, and E. chaffeensis obtained from blood samples of Tibetan sheep and yaks. BLASTn analysis of the 16S rRNA gene showed that the Anaplasma spp. obtained in this study had 99.04\u2013100% identities to either of A. bovis, A. phagocytophilum, A. capra, and E. chaffeensis sequences, respectively. The E. chaffeensis sequences from yaks were 99.44\u2013100% identical to E. chaffeensis isolated from goats (KX505292) in China. Phylogenetic analysis of 16S rRNA gene sequences confirmed A. bovis, A. phagocytophilum, A. capra, and E. chaffeensis in this study (msp4 genomic region of three A. ovis (MZ231113-MZ231115) obtained in this study. The results showed that the three sequences were consistent with the homology of the Iranian A. ovis (MH790273). A. ovis were classified as A. ovis msp4 Genotypes II based on T366C470 . The infection rates of A. bovis, A. phagocytophilum, and A. ovis in yaks in GL and YS were 39.7 and 21.6% (P = 0.001), 34.6 and 19.8% (P = 0.006), 0 and 3.5% (P = 0.005), respectively. In addition, the infection rate of A. bovis and A. phagocytophilum below 4,000 m was significantly higher than those above 4,000 m (P = 0.000). In Tibetan sheep, the infection rate of A. ovis above 4,000 m was higher than that below 4,000 m (P = 0.022) .Anaplasma spp. and E. chaffeensis were investigated in domestic animals in Qinghai, China. Four Anaplasma species and E. chaffeensis were identified in Tibetan sheep and yaks. Among them, E. chaffeensis and A. capra were detected in yaks for the first time in China.In the present study, Anaplasma are widely distributed in domestic animals, wild animals, ticks, and other vectors may be the main vectors of A. ovis.The genus vectors , 30\u201332. (40.5%) and Gans (40.5%) , and Tib (40.5%) . An explus study . In addi A. ovis . The resus study . Whereasn et al. belongs n et al. 25). Ge. GeAnaplo et al. . Remarkan humans , indicatA. phagocytophilum and A. bovis are frequently detected in ruminants around the world. This study confirms that both A. phagocytophilum and A. bovis can infect yaks. The infection rate of A. phagocytophilum in yaks (29.4%) in this study was higher than that reported in sheep (9.9%), dairy cattle (12%), and white yaks (5.3%) in other areas of China (C. pygargus (33.3%) from Heilongjiang China was higher than that in cattle (4.8%) and white yaks (6.2%) from China , and the risk of tick bites with Anaplasma spp. was related to altitude and tick species can be found in the article/supplementary material.The Animal Ethics Committee of the Institute of Zoology, Chinese Academy of Sciences approved the procedures of collecting blood samples from Tibetan sheep and yaks, and obtained the livestock owner's consent. Written informed consent for participation was not obtained from the owners because all the samples in this study were collected by local veterinarians during the daily epidemic surveillance.YW: investigation, conceptualization, methodology, data curation, visualization, writing\u2014original draft, and writing\u2014review & editing. QZ: investigation, methodology, visualization, writing\u2014original draft, and writing\u2014review & editing. YL: investigation, methodology, data curation, and funding acquisition. SH: investigation, methodology, and writing\u2014original draft. BW, GY, PZ, ZY, and HZ: investigation and methodology. YS, XH, and JC: investigation. HH: investigation, visualization, supervision, validation, writing\u2014review & editing, and funding acquisition. All authors contributed to the article and approved the submitted version.This work was supported by the Regular Assistance Project of the International Department of the Ministry of Science and Technology of China (KY201904013), the Chinese Academy of Sciences (CZBZX-1), National Forestry, and Grassland Administration, China.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Fokienia A.Henry & H.H.Thomas is nested within Chamaecyparis Spach, which is in agreement with separate morphological studies. Here the authors confirm a previous taxonomic treatment that incorporated Fokieniahodginsii (Dunn) A.Henry & H.H.Thomas into Chamaecyparis based on the monophyly requirement of taxonomy, i.e. Chamaecyparishodginsii (Dunn) Rushforth. In addition, the type collection of the basionym Cupressushodginsii Dunn was found to contain three sheets of specimens, one in K including a vegetative branch (K000088294) and a separate ovulate cone (K001090486), a second one in A (A00022477), and a third one in IBSC (IBSC0016081). All three specimens are marked with Hongkong Herbarium No. 3505, but only the two specimens in K and IBSC possess similar handwriting of \u201cCupressushodginsii Dunn\u201d. The two specimens should be considered as syntypes according to the Shenzhen Code. The specimen in K is better preserved but it is a mixture according to the collection label: cones from Foochow (Fuzhou) and foliage from Yenping (Nanping). We lectotypified the name Cupressushodginsii with K000088294 because the specimen is well preserved and has enough characters for identification. Moreover, an ovulate cone (K001090486) is on the same sheet.Recent phylogenetic studies have suggested that the monotypic Cupressushodginsii Dunn. Cupressus L. in the cone scale having only two seeds with two very unequal lateral wings, and should be classified into a separate genus, establishing Fokienia A.Henry & H.H.Thomas and transferred the species into this monotypic genus, i.e. F.hodginsii (Dunn) A.Henry & H.H.Thomas. Subsequently this monotypic genus was widely accepted and well known in botanical literature. Both Flora Reipublicae Popularis Sinicae Rushforth. This morphological taxonomy was supported by a few subsequent phylogenetic studies in his China Plant Red Data Book: Rare and Endangered Plants; Chamaecyparishodginsii is widely but sporadically distributed in southern China, Laos, and Vietnam. It has become a vulnerable species for a number of reasons, e.g. habitat loss, over exploitation, many old trees died of diseases, and difficult population regeneration (Fokieniahodginsii (\u2261Chamaecyparishodginsii) as Grade II of protection.neration . The recCupressushodginsii Dunn, Shenzhen Code Rushforth, J. Biol. (Vietnam) 29(3): 38 (2007)2AE6AE12-0417-5549-BED4-798580D12C80Cupressushodginsii Dunn, J. Linn. Soc., Bot. 38: 367 (1908); Fokieniahodginsii (Dunn) A.Henry & H.H.Thomas, Gard. Chron. ser. 3, 49: 67 (1911). \u2261China. Fujian : Nanping , April to June 1905, A.E.N. Hodgins, Hong Kong Herb. 3505 .China: Chongqing, Fujian, Guangdong, Guangxi, Guizhou, Hunan, Jiangxi, Sichuan, Yunnan, Zhejiang; Laos; Vietnam."} +{"text": "Light: Science & ApplicationsCorrection to: 10.1038/s41377-021-00656-w published online 14 October 20211, it is reported that this article contains some errors. The correction details are listed below.Following publication of the article1. Reference 10 has been updated as below.Light Sci. Appl.10, 135 (2021).10. Wang, S. et al. Direct observation of chaotic resonances in optical microcavities. 2. Reference 16 has been updated as below.Light Sci. Appl. 10, 4 (2021).16. Wang, B. C. et al. Towards high-power, high-coherence, integrated photonic mmWave platform with microcavity solitons. 3. Reference 17 has been added to the reference list.Nat. Commun. 11, 2336 (2020).17. Chen, H. J. et al. Chaos-assisted two-octave-spanning microcombs. 4. The citations have been updated in the last sentence as below.6,16 and microcomb generation17.In nonlinear processes, it is this field distribution that determines the ultimate efficiency of the process, and knowledge of this will help to engineer phase-matching for processes such as mm Wave generationThe original article has been updated."} +{"text": "Lactuca sativa) is an important staple of American agriculture. Unlike many vegetables, romaine lettuce is typically consumed raw. Phylloplane microbes occur naturally on plant leaves; consumption of uncooked leaves includes consumption of phylloplane microbes. Despite this fact, the microbes that naturally occur on produce such as romaine lettuce are for the most part uncharacterized. In this study, we conducted culture-based studies of the fungal romaine lettuce phylloplane community from organic and conventionally grown samples. In addition to an enumeration of all such microbes, we define and provide a discussion of the genera that form the \u201ccore\u201d romaine lettuce mycobiome, which represent 85.5% of all obtained isolates: Alternaria, Aureobasidium, Cladosporium, Filobasidium, Naganishia, Papiliotrema, Rhodotorula, Sampaiozyma, Sporobolomyces, Symmetrospora and Vishniacozyma. We highlight the need for additional mycological expertise in that 23% of species in these core genera appear to be new to science and resolve some taxonomic issues we encountered during our work with new combinations for Aureobasidiumbupleuri and Curvibasidium nothofagi. Finally, our work lays the ground for future studies that seek to understand the effect these communities may have on preventing or facilitating establishment of exogenous microbes, such as food spoilage microbes and plant or human pathogens.Romaine lettuce ( Fusarium fujikuroi Nirenberg species complex (FFSC) encompasses over fifty phylogenetic species, a number of which were found to be among the principal fungal contaminants of maize grains from rural commodity markets in Kenya (Amsterdam): 670 (1952).Basionym: Cryptococcus ater (Castell. ex W.B. Cooke) Phaff & Fell, in Lodder, The yeasts: a taxonomic study, 2nd edn (Amsterdam): 1120 (1970), syn. nov.Synonyms: Cryptococcus laurentii f. ater Castell. ex W.B. Cooke, Mycopath. Mycol. Appl. 30: 351 (1966), syn. nov.Cryptococcus magnus (Lodder & Kreger-van Rij) Baptist and Kurtzman, Mycologia 68(6): 1200 (1977) [1976].Cryptococcus laurentii (Kuff.) C.E. Skinner was combined as Papiliotrema laurentii (Kuff.) Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout by Liu et al. [C. ater [= C. laurentii f. ater] represented another species. The new synonymy was proposed based on sequence data and phylogenetic evidence. The ex-type ITS sequences of C. ater and F. magnum were 98R_130655 presenteanalysis B. Howeveaurentii .MycoBank MB836093For description see: Int. J. Syst. Evol. Microbiol. 54 (3): 989 (2004).Holotype: PYCC 5690, permanently preserved in a metabolically inactive state at the Portuguese Yeast Culture Collection. Ex-type culture: CBS 9648.Auriculibuller fuscus J.P. Samp., J. In\u00e1cio, Fonseca & Fell, Int. J. Syst. Evol. Microbiol. 54 (3): 989 (2004), nom. inval., Art. 40.6 (Shenzhen).Synonyms: Papiliotrema fusca Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout, Stud. Mycol. 81: 126 (2015), nom. inval., Art. 40.6 (Shenzhen).Acremonium Link, Alternaria, Aureobasidium, Cladosporium , Cryptococcus Vuill., Rhodotorula and Sporobolomyces , Rhodotorula [in part as Sampaiozyma] and Sporobolomyces [in part as Symmetrospora] represent 85.5% of total isolates and, as a result, can be considered the core community [fide 18] (Previous culture-based studies have found that the phylloplane of crops is dominated by species of st-like) ,37,38,39mycetes) ,33. Undefide 18] . Of thesAlternaria , each representing a different species\u2014five isolates were from conventional lettuce samples, one was from a hydroponic sample. Alternaria is a large genus of filamentous fungi with about 366 accepted species [A. alternariae (Cooke) Woudenb. & Crous and A. tenuis Nees [syn. of Alternaria alternata (Fr.) Keissl.]. Several species are major pathogens of fresh fruit, eggplants, peppers and fresh vegetables and N. liquefaciens (Saito & M. Ota) Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout . Our third isolate (HU9305), from a hydroponic lettuce sample, was most similar to R. diobovata (S.Y. Newell & I.L. Hunter) Q.M. Wang, F.Y. Bai, M. Groenew. & Boekhout, with three mismatches\u2014thus, also representing an undescribed species.We obtained three isolates from three lettuce samples, each representative of another, potentially undescribed species . Two isoto group A, which n et al. , 1\u20133 misR_077096 ), respecRhodotorula is a ubiquitous saprobic genus that is isolated from many different habitats, including in extreme conditions [Rhodotorula sp. suppresses other yeast species and increases russet formation on apples. A number of studies have mentioned biocontrol properties of Rhodotorula \u201cglutinis\u201d although their identifications may be erroneous because this species is rarely isolated compared to other morphologically similar species of red yeast [Rhodotorula often occurs on the phylloplane and other types of plant substrates and species have been isolated from lettuce leaves in previous studies [Lactuca sativa cv. \u201cOutredgeous\u201d) was grown in rooting pillows in a plant growth chamber on the International Space Station, harvested, brought back to earth and analyzed to genus-level. Of ten genera isolated from lettuce leaves and roots, Rhodotorula was the most common. Urbina and Aime [Rhodotorula species, some of which have been reported as emerging (opportunistic) pathogens for both humans and animals [nditions . Gildemanditions reporteded yeast . Rhodoto studies ,106,107. studies ; red romand Aime reported animals ,111,112.Sampaiozyma (Microbotryomycetes incertae sedis) was one of the genera introduced by Wang et al. [Rhodotorula, isolated from stagnant water and leaf surfaces of pasture plants [S. ingeniosa (Di Menna) Q.M. Wang, F.Y. Bai, M. Groenew. & Boekhout and S. vanillica (J.P. Samp.) Q.M. Wang, F.Y. Bai, M. Groenew. & Boekhout. Sampaiozyma is most closely related to Leucosporidium Fell, Statzell, I.L. Hunter & Phaff. Wang et al. [Leucosporidium with high support in their ribosomal DNA and seven-locus phylogenies. Liu et al. [Leucosporidium and Sampaiozyma. The ex-type ITS sequences of S. ingeniosa and S. vanillica only differ in three nucleotides. We obtained two isolates of Sampaiozyma, one from a conventional lettuce sample, the other from a hydroponic sample. The two isolates each represent an undescribed species because it was polyphyletic in the traditional sense, occurring in most of the yeast-forming classes of Pucciniomycotina, as well as in Agaricomycotina, Ustilaginomycotina and, most recently, in Pezizomycotina [Sporobolomyces included sixteen species. Six more species have been described by Lorenzini et al. [Sporobolomyces [Wang et al. revised mycotina ,99,116. i et al. and Li ei et al. bringingolomyces . The redolomyces ,118,119.olomyces ,121. Becolomyces ,123,124.Sporobolomyces species are free-living and worldwide in distribution. They are reported from many different habitats\u2014including freshwater and marine ecosystems, excrements of maize pests, fruit must, soil, buildings and air\u2014although most commonly from the plant phylloplane [Sporobolomyces start to increase when cereal leaves reach their half-age. The promise of S. roseus Kluyver & C.B. Niel as a biocontrol against postharvest diseases of pome fruits has been shown by Janisiewicz et al. [Penicillium expansum Link (blue mold) and from 92% to 4% to Botrytis cinerea Pers. (gray mold). Important to note is that, in addition to the leaf age, humidity is also an important factor in the growth of S. roseus. Bashi and Fokkema [Sporobolomyces can only use nutrients that are present on the leaves at relative humidity of at least 90%.lloplane ,130,131.lloplane suggestez et al. . After y Fokkema experimeSporobolomyces was the most abundantly recovered genus in our culture-based community, representing more than a quarter of all isolates (26.9%). Sixty-seven isolates were obtained from 27 of 42 lettuce samples (64.3%). Whereas the number of isolates was the highest of any genus isolated in this study, the number of species was only two. Both species appeared to be undescribed (Sporobolomyces sp. nov. 1 was represented by a single isolate (HU9138), obtained from an organic lettuce sample. It shares 98.82% identity with S. patagonicus Libkind, Van Broock & J.P. Samp. isolated from subsurface water in Argentina. Sporobolomyces sp. nov. 2 was detected on eleven organic lettuce samples (30 isolates) and sixteen conventional samples (36 isolates). Through a BLAST search in NCBI GenBank (100% identity hits), we found that this same yeast has a broad geographic distribution and is found from different habitats: on a wilting leaf of Parthenocissus sp. in China [Prunus avium L. cherries in Spain [Vitis vinifera L. grapes in Washington [Quercus faginea Lam. leaves in Portugal [Antirrhinum L. flowers in California, Septoria blasdalei-diseased leaves of Ceanothus arboreus Greene in California [escribed . Sporoboin China , Prunus in Spain , Vitis vshington , glaciershington , QuercusPortugal , Antirrhlifornia and guavSymmetrospora . Symmetrospora was introduced by Wang et al. [Rhodotorula and Sporobolomyces of the \u201cgracilis/marina clade\u201d [Symmetrospora, bringing the total to 11 recognized species. Symmetrospora is known in North and South America, Europe, Asia and Australia and species in the genus have been isolated from a wide diversity of habitats\u2014leaf surfaces, air, marine water, beetle guts and a sea sponge [S. cf. coprosma [S. coprosmae (Hamam. & Nakase) Q.M. Wang, F.Y. Bai, M. Groenew. & Boekhout but seeR_073317 ,146.Vishniacozyma from 18 lettuce samples, of which nine isolates were obtained from eight conventional lettuce samples and 18 from ten organic ones. Liu et al. [Vishniacozyma to accommodate eleven species previously known as members of Bullera Derx and Cryptococcus. Currently, the genus Vishniacozyma contains sixteen species [Vishniacozyma carnescens (Verona & Luchetti) Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout (three isolates); V. cf. foliicola Q.M. Wang & F.Y. Bai ex Yurkov (6 isolates); V. aff. heimaeyensis Vishniac ex Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout sp. nov. (one isolate); V. tephrensis Vishniac ex Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout (one isolate); and V. victoriae Xin Zhan Liu, F.Y. Bai, M. Groenew. & Boekhout (16 isolates). Isolate HU9248 had seven mismatches with V. heimaeyensis in its ITS, which indicated that it represented a different species, which was confirmed by the evolutionary distance among both isolates revealed from the ITS phylogenetic analysis . Within this core community, the yeast-like taxa dominate (with 64.8% of isolates). Interestingly, management treatment has no effect on the number of fungal isolates (t(20) = 0.2473, p = 0.8072), nor on the number of species (t(20) = 0.8051, p = 0.4302). However, we emphasize that these results may be biased due to the nature of this study; we may not have cultured every species that was effectively present on lettuce leaves . Treatments potentially driving changes in fungal communities are best studied using a high-throughput sequencing approach .Sporobolomyces, we recovered 66 isolates from 27 romaine lettuce samples. This species represented 26.5% of our total isolates and 31.0% of our \u201ccore\u201d culture-based community. An earlier study also reported Sporobolomyces to be a dominant portion of the lettuce phylloplane, with 35.5% to 63.0% representation of the total community depending on the cultivar [E. coli to enter and persist in these phylloplane fungal communities as part of an outbreak control strategy.Based on over a decade of fieldwork in understudied habitats and regions, Urbina and Aime estimatecultivar . It is i"} +{"text": "Coccinellidae fauna comprises a total of 101 species: 83 from the Mainland, 39 from Madeira, and 32 from the Azores. The listed species are distributed among 2 sub-families and 13 tribes: within the subfamily Microweiseinae, Madeirodulini (1 species), Serangiini (2 species), and within the subfamily Coccinellinae, Azyini (1 species), Chilocorini (4 species), Coccidulini (7 species), Coccinellini (30 species), Epilachnini (4 species), Hyperaspidini (7 species), Noviini (2 species), Platynaspini (1 species), Scymnini (37 species), Stethorini (3 species), and Sticholotidini (2 species). The Portuguese fauna comprises 10 exotic species: 5 present in the Mainland, 7 in Madeira, and 6 in the Azores. Harmoniaaxyridis from Madeira, Propyleaquatuordecimpunctata from the Azores, Delphastuscatalinae from the Azores and Madeira, Nephus (Geminosipho) reunioni and Nephus (Nephus) voeltzkowi Weise, 1910 from Madeira and Microserangium sp. from the Mainland, are reported for the first time. Some species are considered doubtful records, as explained in the text. These results were obtained by compiling information on the available literature regarding ladybeetle species on the Portuguese mainland and insular territories, and original data.A comprehensive annotated checklist of the ladybeetle species of Portugal, including the Azores and Madeira archipelagos, is presented. The Coleoptera: Coccinellidae) fauna of Portugal. Since then, several studies on Portuguese ladybeetles have been published, including catalogues , scale insects (Coccoidea), whiteflies (Aleyrodoidea) or mites (Acari). Largely used in biological control programmes, ladybeetles render important ecosystem services to agriculture and silviculture (Novius (=Rodolia) cardinalis (Mulsant) was introduced in California from Australia to control the cottony cushion scale, Iceryapurchasi Maskell, also of Australian origin , doubtful records with an asterisk (*) and exotic species with a dollar ($). The bibliographic references associated with each species recorded for Portugal are presented in Table For each species, we specify the regions where the species were recorded , under \u201cDistribution\u201d and we provide brief notes about the status of the species in each region, possible taxonomic incongruences, and the current biogeographical (limits as in L\u00f6bl and Smetana 2007) distribution under \u201cComments\u201d. New records are marked with a black spot CryptognathacatalinaeHorn 1895= Distribution. Madeira\u25cf and Azores\u25cf.Comments. A native species of Nearctic and Neotropical regions, currently established in the Palearctic region following introductions in biological control programs. Its presence in the Azores probably originated from deliberate releases for biological control of whiteflies. A large population was first recorded by Isabel Borges, from kales in a vegetable garden , August 2018, where both adults and larvae were abundant. In Madeira, D\u00e9lia Cravo collected in October 2006 from Musaacuminata Colla and Jos\u00e9 Jesus collected in September 2020 on Citrusreticulata Blanco, . First records for Portugal.$Microserangium sp.Microserangium Miyatake, 1961= Distribution. Mainland\u25cf.Comments. Oriental origin. First observations by Vera Zina, in 2012, Algarve. A few individuals were collected in August 2012, and May, July and November 2013 from the canopy of citrus . First record for Portugal.$Cryptolaemusmontrouzieri Mulsant, 1853Distribution. Mainland.Comments. Currently established in Palearctic, Afrotropical, Nearctic and Neotropical regions. This exotic species of Australian origin, used around the world for biological control since the 19th century, was introduced from France in the early 20th century for the biological control of the citrus mealybug, Planococcuscitri (Risso) ( (Risso) , but the (Risso) .Chilocorusbipustulatus Coccinellabipustulata Linnaeus, 1758= Distribution. Mainland, Madeira and Azores.Comments. Palearctic, Afrotropical, and Nearctic distribution.Exochomusquadripustulatus Coccinellaquadripustulata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic and Nearctic distribution.Parexochomusnigripennis Chilocorusnigripennis Erichson, 1843= Distribution. Mainland.Comments. Palearctic and Afrotropical distribution.Parexochomusnigromaculatus Coccinellanigromaculata Goeze, 1777= Distribution. MainlandComments. Palearctic distribution.Coccidularufa Dermestesrufus Herbst, 1783= Distribution. Mainland.Comments. Palearctic distribution.Coccidulascutellata Chrysomelascutellata Herbst, 1783= Distribution. Mainland.Comments. Palearctic distribution.Iberorhyzobiusrondensis Coccidularondensis Eizaguirre, 2004= Distribution. Mainland.Comments. This is an endemic species of the Iberian Peninsula, associated with maritime pine forests, and is a specialist predator of the maritime pine bast scale, Matsucoccusfeytaudi Ducasse Strongyluschrysomeloides Herbst, 1792= Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution.$Rhyzobiusforestieri Platyomusforestieri Mulsant, 1853= Distribution. Azores.Comments. Palaearctic, Nearctic and Australian distribution. This exotic species of Australian origin was introduced in Europe in the 1980\u00b4s for the biological control of scale insects (Coccoidea), and became established in different countries, including Italy, France, Greece and Albania Nitidulalitura Fabricius, 1787= Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution.$Rhyzobiuslophanthae Scymnuslophanthae Blaisdell, 1892= Distribution. Mainland, Madeira and Azores.Comments. Palaearctic, Afrotropical, Nearctic, Neotropical, and Australian distribution. This species, native to Queensland, Australia (Coccoidea: Diaspididae) and imported to Portugal in the 1930\u2019s and 1980\u2019s Coccinellabipunctata Linnaeus, 1758= Distribution. Mainland, Madeira and Azores.Comments. Worldwide distributed .Adaliadecempunctata Coccinelladecempunctata Linnaeus, 1758= Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution.Adaliatestudinea Coccinellatestudinea Wollaston, 1854= Distribution. Madeira.Comments. Macaronesian endemic species.Anatisocellata Coccinellaocellata Linnaeus, 1758=Distribution. Mainland.Comments. Palearctic distribution.Anisostictanovemdecimpunctata Coccinellanovemdecimpunctata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.Calviadecemguttata Coccinelladecemguttata Linnaeus, 1767= Distribution. Mainland.Comments. Palearctic distribution.Calviaquatuordecimguttata Coccinellaquatuordecimguttata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic, Nearctic and Oriental distribution.Calviaquindecimguttata Coccinellaquindecimguttata Fabricius, 1777= Distribution. Mainland.Comments. Palearctic distribution.Ceratomegillanotata Coccinellanotata Laicharting, 1781= Distribution. Mainland.Comments. Palearctic distribution.Ceratomegillaundecimnotata Coccinellaundecimnotata Schneider, 1792= Distribution. Mainland and Azores.Comments. Palearctic distribution.Coccinellagenistae Wollaston, 1854Distribution. Madeira.Comments. Macaronesian endemic species.Coccinellaseptempunctata Linnaeus, 1758Distribution. Mainland, Madeira and Azores*.Comments. Palearctic, Afrotropical, Nearctic and Oriental distribution. Relatively important species in cereal crops in the Azores, especially in the first half of the 20th century, having eventually disappeared when these crops became scarce Coccinellaquatuordecimpustulata Linnaeus, 1758= Distribution. Mainland and Madeira*.Comments. Palearctic and Afrotropical distribution. Although previously recorded in the Madeira archipelago, there are doubts regarding its present occurrence. It might have been introduced but did not establish .Coccinulasinuatomarginata Coccinellasinuatomarginata Faldermann, 1837= Distribution. Mainland and Madeira*.Comments. Palearctic distribution. Although previously recorded for the Madeira archipelago, there are doubts as to its present occurrence. It might have been introduced but did not establish .$Eriopisconnexa Coccinellaconnexa Germar, 1824= Distribution. Azores*.Comments. Of Neotropical origin where it is very common. Although previously reported for the Azores, it did not become established .Halyziasedecimguttata Coccinellasedecimguttata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.$Harmoniaaxyridis Coccinellaaxyridis Pallas, 1773= Distribution. Madeira\u25cf.Comments. Worldwide distribution. Several specimens collected by Miguel M. Andrade, in September 2019, from Enterolobium sp. , Gra\u00e7a Freitas and Franquinho Aguiar, collected in September and October 2020, from Annonacherimola Mill. . Harmoniaaxyridis is the most invasive insect of the world Coccinellaquadripunctata Pontoppidan, 1763= Distribution. Mainland, Madeira.Comments. Palearctic and Nearctic distribution.Hippodamiavariegata Coccinellavariegata Goeze, 1777= Distribution. Mainland, Madeira and Azores.Comments. Palearctic, Afrotropical, Nearctic and Oriental distribution.Myrrhaoctodecimguttata Coccinellaoctodecimguttata Linnaeus, 1758= Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution.Myziaoblongoguttata Coccinellaoblongoguttata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.Oenopiaconglobata Coccinellaconglobata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.Oenopiadoublieri Harmoniadoublieri Mulsant, 1846= Distribution. Mainland and Azores.Comments. Palearctic distribution.Oenopialyncea Coccinellalyncea Olivier, 1808= Distribution. Mainland.Comments. Palearctic distribution.Propyleaquatuordecimpunctata Coccinellaquatuordecimpunctata Linnaeus, 1758= Distribution. Mainland and Azores\u25cf.Comments. Palearctic and Nearctic distribution. First record for the Azores. Several adults were collected in July 2019 by Ant\u00f3nio O. Soares and Isabel Borges, in a vegetable garden, of the parish of Castelo Branco , Faial Island.Psylloboravigintiduopunctata Coccinellavigintiduopunctata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.Sospitavigintiguttata Coccinellavigintiguttata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic distribution.Tytthaspissedecimpunctata Coccinellasedecimpunctata Linnaeus, 1761= Distribution. Mainland.Comments. Palearctic distribution.Vibidiaduodecimguttata Coccinelladuodecimguttata Poda von Neuhaus, 1761= Distribution. Mainland.Comments. Palearctic and Oriental distribution.Chnootribaelaterii Coccinellaelaterii Rossi, 1794= Distribution. Mainland.Comments. Palearctic and Afrotropical distribution. Reported by portugalensis. Based on molecular and morphological data, it was suggested to transfer this species to the genus Chnootriba Epilachnaangusticollis Reiche, 1862= Distribution. Mainland.Comments. Distributed in the Mediterranean region.Henosepilachnaargus Coccinellaargus Geoffrey, 1785= Distribution. Mainland.Comments. Palearctic and Afrotropical distribution.Subcoccinellavigintiquatuorpunctata Coccinellavigintiquatuorpunctata Linnaeus, 1758= Distribution. Mainland.Comments. Palearctic and Nearctic distribution.Hyperaspisconcolor Coccinellaconcolor Suffrian, 1843= Distribution. Mainland.Comments. Palearctic distribution.Hyperaspisduvergeri F\u00fcrsch, 1985Distribution. Mainland.Comments. Palearctic distribution.Hyperaspishoffmannseggi Coccinellahoffmannseggi Gravenhorst, 1807= Distribution. Mainland.Comments. Palearctic distribution.Hyperaspisillecebrosa Mulsant, 1846Distribution. Mainland.Comments. Palearctic distribution. illecebrosa Mulsant, 1846 and castiliana Eizaguirre ssp. nov.; only the first one is mentioned for Portugal.$Hyperaspispantherina F\u00fcrsch, 1975, following F\u00e9lix et al. (2008)Distribution. Madeira.Comments. Established in Palearctic/Madeira, originally from Afrotropical region. The first record for Europe was in 2002, in Madeira archipelago (Insignortheziainsignis (Browne 1887).hipelago . In MadeHyperaspisreppensis Coccinellareppensis Herbst, 1783= Distribution. Mainland*.Comments. Palearctic distribution. According to H.illecebrosa.Hyperaspisstigma Coccinellastigma Olivier, 1808= Distribution. Mainland.Comments. Palearctic distribution.$Noviuscardinalis , following Pang et al. (2020)Vedaliacardinalis Mulsant, 1850= Distribution. Mainland, Madeira and Azores.Comments. Established in Palaeartic, Afrotropical, Nearctic and Neotropical, Oriental. Native to Australian region. This exotic species was introduced in California and South Africa in the 1890\u00b4s for the control of the cottony cushion scale, Iceryapurchasi Maskell Coccinellaluteorubra Goeze, 1777= Distribution. Mainland.Comments. Palearctic distribution.Clitostethusarcuatus Coccinellaarcuata Rossi, 1794=Distribution. Mainland, Madeira and Azores.Comments. Palearctic, Afrotropical, Nearctic distribution.Nephus (Bipunctatus) bisignatus Scymnusbisignatus Boheman, 1850= Distribution. Mainland and Azores.Comments. Palearctic distribution.Nephus (Bipunctatus) conjunctus Scymnusconjunctus Wollaston, 1870= Distribution. Mainland and Madeira.Comments. Palearctic and Afrotropical distribution. This species was first reported as N. (bipunctatus) includens (Kirsch 1871) based on adults emerged from larvae collected in 1988 from citrus fruits infested with mealybugs, in the South of Portugal (Algarve) (N. (bipunctatus) includens is a junior synonym of N.conjuntus. Taking this into account and knowing that specimens previously collected in 1984 in the Algarve and identified as N.quadrimaculatus Herbst were in fact shown to be N.includens (Algarve) . Howeverncludens , we havencludens .Nephus (Bipunctatus) peyerimhoffi Scymnuspeyerimhoffi Sicard, 1923= Distribution. Mainland.Comments. Palearctic and Afrotropical distribution.$Nephus (Geminosipho) reunioni Scymnusreunioni F\u00fcrsch, 1974a= Distribution. Mainland, Azores and Madeira\u25cf.Comments. Palearctic and Afrotropical distribution. The first record in Europe was in France in 1983 mentions that the distribution of N.reunioni is apparently restricted to Reunion Island and Mauritius, and that the references to its presence in South Africa and other Mediterranean countries, such as Portugal and Israel, are due to misidentifications by the author himself, which most likely correspond to N.derroniN.reunioni made by F\u00fcrsch in Chazeau et al. (1974). N.reunioni for Portugal, also illustrated the external morphology and genitalia corresponding to the original description by F\u00fcrsch in Chazeau et al. (1974). In both cases, the observations showed that the specimens from the Portuguese population are distinct from N.derroni. In Madeira, collected by Aguiar and Jesus, in October 2008, from Dombeyawallichii (Lindl.) Baill. , Celestina Braz\u00e3o in February 2003, from Dombeyawallichii (Lindl.) Baill. , Aguiar and Jesus, in April 2005, from Oleaeuropaea L. , D\u00e9lia Cravo, in September 2006, from Jacarandamimosifolia D. Don , J.D. Sardinha, in January 2010, from Perseaamericana Mill. , Gra\u00e7a Freitas, in August 2011, from Perseaamericana Mill. , Gra\u00e7a Freitas, in July 2013, from Perseaamericana Mill. , Paula Rocha, in January 2015, from Annonacherimola Mill. , Florasanto, in June 2015, from Pinuspinaster Aiton , Nat\u00e1lia Nunes, in January 2016, from Laurusnovocanariensis Rivas Mart., Lous\u00e3, Fern. Prieto, E. D\u00edaz, J.C. Costa & C. Aguiar , Celestina Braz\u00e3o, in August 2017, from Neriumoleander L. , F\u00e1tima Rocha, in November 2019, from Psidiumguajava L. , Gra\u00e7a Freitas, in September 2020, from Annonacherimola Mill. , and Alexandra Magro and Miguel Sequeira, in September 2018, from herbaceous plants . New record for Madeira. in 1983 . This sp in 1983 . Its pre in 1983 . In his Nephus (Nephus) binotatus Scymnusbinotatus Brisout de Barneville, 1863= Distribution. Mainland.Comments. Palearctic distribution.Nephus (Nephus) flavopictus Scymnusflavopictus Wollaston, 1854= Distribution. Madeira and Azores.Comments. Macaronesian endemic species.Nephus (Nephus) quadrimaculatus Sphaeridiumquadrimaculatum Herbst, 1783= Distribution. Mainland.Comments. Palearctic distribution.Nephus (Nephus) schatzmayri Canepari & Tedeschi, 1977Distribution. Mainland.Comments. Palearctic distribution.Nephus (Nephus) ulbrichi F\u00fcrsch, 1977Distribution. Mainland.Comments. Palearctic distribution.$Nephus (Nephus) voeltzkowi Weise, 1910, following Magro et al. (2020b)Distribution. Azores and Madeira\u25cf.Comments. Afrotropical origin. Very recently, two parthenogenetic populations of this species were found in the Azores and Mascarene archipelagos, becoming the first reported case of asexuality in the Coccinellidae , and Alexandra Magro and Miguel Sequeira in September 2018, from herbaceous plants . New record for Madeira.nellidae . ObservaNephus (Sidis) depressiusculus Scymnusdepressiusculus Wollaston, 1867= Distribution. Madeira.Comments. Palearctic and Afrotropical distribution.Nephus (Sidis) hiekei Scymnushiekei F\u00fcrsch, 1965= Distribution. Mainland.Comments. Palearctic distribution.Nephus (Sidis) pooti F\u00fcrsch, 1999Distribution. Mainland.Comments. Palearctic distribution.Scymniscusfuerschi Nephusfuerschi Plaza, 1981= Distribution. Mainland.Comments. Palearctic distribution.Scymniscushelgae Scymnushelgae F\u00fcrsch, 1965= Distribution. Mainland and Azores.Comments. Palearctic distribution.Scymniscussemirufus Scymnussemirufus Weise, 1885=Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Mimopullus) epistemoides Wollaston, 1867Distribution. Madeira.Comments. Palearctic distribution.Scymnus (Mimopullus) limnichoides Wollaston, 1854Distribution. Madeira.Comments. Palearctic distribution.Scymnus (Mimopullus) marinus Rhyzobiusmarinus Mulsant, 1850= Distribution. Mainland and Madeira.Comments. Palearctic distribution.Scymnus (Neopullus) ater Kugelann, 1794Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Neopullus) haemorrhoidalis Herbst, 1797Distribution. Madeira and Azores.Comments. Palearctic distribution.Scymnus (Neopullus) limbatus Stephens, 1832Distribution. Madeira.Comments. Palearctic distribution.Scymnus (Parapullus) abietis Coccinellaabietis Paykull, 1798= Distribution. Mainland and Madeira.Comments. Palearctic distribution.Scymnus (Pullus) auritus Thunberg, 1795Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Pullus) subvillosus Coccinellasubvillosa Goeze, 1777= Distribution. Mainland, Madeira and Azores.Comments. Palearctic and Afrotropical distribution.Scymnus (Pullus) suturalis Thunberg, 1795Distribution. Mainland, Madeira and Azores.Comments. Palearctic and Nearctic distribution.Scymnus (Scymnus) apetzi Mulsant, 1846Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Scymnus) bivulnerus Baudi di Selve, 1894Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Scymnus) frontalis Coccinellafrontalis Fabricius, 1787= Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Scymnus) interruptus Coccinellainterrupta Goeze, 1777= Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution.Scymnus (Scymnus) laetificus Weise, 1879Distribution. Mainland.Comments. Palearctic distribution. However, it only occurs in the Western Mediterranean.Scymnus (Scymnus) nubilus Mulsant, 1850Distribution. Mainland, Madeira and Azores.Comments. Palearctic distribution. On Portugal\u2019s mainland, this species was wrongly identified as Scymnuslevaillanti Mulsant.Scymnus (Scymnus) rubromaculatus Coccinellarubromaculata Goeze, 1777= Distribution. Mainland, Madeira and Azores.Comments. Palearctic and Afrotropical distribution.Scymnus (Scymnus) rufipes Coccinellarufipes Fabricius, 1798= Distribution. Mainland.Comments. Palearctic distribution.Scymnus (Scymnus) schmidti F\u00fcrsch, 1958Distribution. Mainland and Azores.Comments. Palearctic distribution.Scymnus (Scymnus) suffrianioides Sahlberg, 1913Distribution. Mainland.Comments. Palearctic distribution.Stethoruspusillus Scymnuspusillus Herbst, 1797= Distribution. Mainland and Azores.Comments. Palearctic distribution.Stethorustenerifensis F\u00fcrsch, 1987Distribution. Madeira.Comments. Macaronesian endemic species.Stethoruswollastoni Kapur, 1948Distribution. Madeira.Comments. Macaronesian endemic species.Coelopterussalinus Mulsant & Rey, 1852Distribution. Mainland.Comments. Palearctic and Afrotropical distribution.Pharoscymnusdecemplagiatus Scymnusdecemplagiatus Wollaston, 1857= Distribution. Madeira and Azores.Comments. Palearctic distribution.In Memoriam of Armando Am\u00e9rico Cardoso Raimundo (2.V.1942\u20139.Xi.2019): A farewell to colleague and friend.Microserangium sp. and Jaroslav V\u011btrovec of Harmoniaaxyridis Pallas from Madeira.Thanks are due to Claudio Canepari for helping in the identification of This study was financed by FEDER in 85% and by Azorean Public funds by 15% through Operational Program Azores 2020, under the following projects AZORESBIOPORTAL \u2013PORBIOTA (ACORES-01-0145-FEDER-000072), and under the project ECO2 \u2013 TUTA (ACORES-01-0145-FEDER-000081). The Forest Research Centre is funded by Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia I.P. (FCT), Portugal (UIDB/00239/2020). Thanks are also due to FCT/MCES for financial support to CESAM (UIDB/50017/2020+UIDP/50017/2020) through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. OMCCA is funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. AM was supported by the \u201cLaboratoires d\u2019Excellence\u201d LabEx TULIP (ANR-10-LABX-41). The Open Access of this manuscript was supported by the project FCT-UIDB/00329/2020-2024."} +{"text": "The lack of organs for transplantation is an important problem in medicine today. The growth of organsin chimeric animals may be the solution of this. The proposed technology is the interspecific blastocyst complementation method in combination with genomic editing for obtaining \u201cfree niches\u201d and pluripotent stem cellproduction methods. The CRISPR/Cas9 method allows the so-called \u201cfree niches\u201d to be obtained for blastocystcomplementation. The technologies of producing induced pluripotent stem cells give us the opportunity to obtain human donor cells capable of populating a \u201cfree niche\u201d. Taken together, these technologies allow interspecificblastocyst complementation between humans and other animals, which makes it possible in the future to growhuman organs for transplantations inside chimeric animals. However, in practice, in order to achieve successfulinterspecific blastocyst complementation, it is necessary to solve a number of problems: to improve methods forproducing \u201cchimeric competent\u201d cells, to overcome specific interspecific barriers, to select compatible cell developmental stages for injection and the corresponding developmental stage of the host embryo, to prevent apoptosis of donor cells and to achieve effective proliferation of the human donor cells in the host animal. Also, it isvery important to analyze the ethical aspects related to developing technologies of chimeric organisms with theparticipation of human cells. Today, many researchers are trying to solve these problems and also to establish newapproaches in the creation of interspecific chimeric organisms in order to grow human organs for transplantation.In the present review we described the historical stages of the development of the blastocyst complementationmethod, examined in detail the technologies that underlie modern blastocyst complementation, and analyzedcurrent progress that gives us the possibility to grow human organs in chimeric animals. We also considered thebarriers and issues preventing the successful implementation of interspecific blastocyst complementation in practice, and discussed the further development of this method The first studies on generating chimeric animals were carriedout in the 60s of the last century . Since then, a significantamount of scientific knowledge on chimerism has been accumulated, modern definitions have been formulated andvarious classifications of chimeras have been proposed.Chimeric animals are composed of genetically differentcells originating from two or more different zygotes . There are different classifications of chimerism,depending on the number and type of donor cells and theirdistribution in chimeric organisms. Chimerism can benatural or artificial. Natural chimerism is represented bytwo forms: tetragametism and microchimerism. Tetragametism results from the fertilization of two separate eggsby two different spermatozoa, followed by the developmentof a single organism with mixed cell lines . Microchimerism is a phenomenon that occurs whena small number of cells from another individual are presentin a multicellular organism. Examples of natural microchimerism are twin chimerism andfeto-maternal microchimerism . Theartificial chimerism occurs for example as a result of organor tissue transplantation or blood transfusions. The chimerism can be partial or systemic depending onthe degree of donor cells distribution in a chimeric organism . For example, during organor tissue transplantation the distribution of donor cells islimited to a particular organ or tissue which results in partial chimerism. Systemic chimerism can be observed, forexample, during the fusion of embryos at an early stage ofdevelopment. As a result of such a fusion, an embryo withcell lines which distributed over different organs and tissuesis formed, with these lines originating from two differentzygotesChimerism can be primary and secondary. Primary chimerism occurs in the early stages of embryogenesis, andsecondary chimerism occurs after the onset of gastrulation. Chimerism can be intraspecies and interspecies. The intraspecies chimeras consist ofcell lines originating from different zygotes of the samespecies. Interspecies chimeras consist of cell lines originating from two or more zygotes of representatives of differentspecies.The most popular methods to obtain chimera under laboratory conditions are cell aggregation andmicroinjection into the embryo . Aggregation methods for producing chimeras are technically easier,do not require expensive micromanipulation equipment,and sometimes can work more efficiently than injectionmethods . However, in some cases,for example, when obtaining interspecies chimeras, thetrophectoderm with donor cells can impede implantation,and in this case injection methods are preferred . In addition, the injection methods allow tocontrol the number of injected cells.In their study Okumura and colleagues compared thedegree of distribution of rat cells in chimeric rat-mouseembryos by different methods: the 8-cell aggregation method, injection into an 8-cell embryo, and injection into ablastocyst. According to the study, the degree of chimerismwas highest when researchers used the injection methodinto an 8-cell embryo, although the percentage of chimericmice was higher when they injected cells into the blastocyst.The most common and promising method to generatehuman organs for transplantation in the organisms of interspecies chimeric animals is injection into the blastocyst \u2013 socalled the blastocyst complementation method. Further inthis review this method is considered first in its applicationto the rodents, then the development of techniques related tothis method is described: obtaining \u201cfree niches\u201d of animalsand obtaining \u201cchimera-competent\u201d human cells. Thesetechniques made it possible to perform the interspecies blastocyst complementation between humans and other animals.Intraspecies chimeras. In 1993 the method of intraspeciesblastocyst complementation was successfully demonstratedfor the first time. The main idea of the method was thatwild type mouse embryonic stem (ES) cells were injectedinto the blastocyst derived from Rag2\u200a\u2013/\u2013 immunodeficientmouse with T and B lymphocytes deficiency. As a result,donor T and B lymphocytes were observed in chimericanimals . An important result of this study was that donor ES cells were able to differentiate intoT and B lymphocytes, using the vacant lymphoid T and Bcell niche in an immunodeficient organism. It demonstratedthe possibility of generating organs in the body of chimeric animals with so-called \u201cfree niches\u201d. Then, in 2007,blastocyst complementation was used to grow pancreaticepithelium in Pdx1\u200a\u2013/\u2013 deficient mice with impaired pancreasdevelopment . In 2012, successfulintraspecies blastocyst complementation of ES cells froma healthy mouse into the blastocyst of a Sall1\u200a\u2013/\u2013 deficientmouse with impaired renal development was demonstrated.Interspecies chimeras. In 2010, for the first time viableinterspecies chimeras with a developed rat pancreatic epithelium were obtained in the body of a Pdx1\u200a\u2013/\u2013 deficient mouseby blastocyst complementation .In this study, scientists successfully injected rat pluripotentES cells into murine Pdx1\u200a\u2013/\u2013 blastocysts that were genetically modified to impair pancreas development. In 2011,interspecies blastocyst complementation was used to injectrat ES cells into the blastocyst of a nude mouse without athymus, and a chimeric mouse with a functioning thymusof rat origin was obtained . Recently,it was reported about the successful generation of a mousekidney in the chimeric organism of Sall1\u200a\u2013/\u2013 rat by interspecies blastocyst complementation .In 2017, a Nakauchi group demonstrated the successfultransplantation of pancreatic tissue generated from pluripotent stem cells in Pdx1\u200a\u2013/\u2013 deficient rats to diabetic mice. These results proved the possibility of using tissues generated in the body of interspecieschimeric animals for organ transplantation.Further in the review, the following technologies underlying modern blastocyst complementation are discussed indetails: obtaining animals with so-called \u201cfree niches\u201d andobtaining \u201cchimera-competent\u201d cells for injection into theblastocyst.The animals with \u201cfree niches\u201d in organogenesis, that iswith the absence or partial development of certain organsor special cell lines, are necessary for obtaining chimericanimals by the method of blastocyst complementation. Suchanimals with \u201cfree niches\u201d in organogenesis are possible toobtain by turning off the expression of genes involved inorganogenesis. Certain types of stem cells in these animalslose the ability to specialize, proliferate or differentiate, thatis, they cannot participate in organogenesis and the organdoes not developWhen donor cells with normal organogenesis are injectedinto the blastocyst of animals with \u201cfree niches\u201d, missingorgans can be formed. For the generation of donor organsin chimeric organisms, it is necessary that the donor\u2019s cellshave an advantage in the organogenesis of a certain tissueor organ, since these cells are introduced in small numbers,and they do not initially have a selective advantage. Thecreation of \u201cfree niches\u201d allows donor cells to proliferate without competition with host cells in a chimeric organismand to form a given organ. A \u201cfree niche\u201d can be createdby the gene knockout method or by methods of genome editing: zinc fingernucleases(ZFN), TALE-associated nucleases and CRISPR/Cas9/CRISPR-associated system (Cas))The obtaining of knockout mice by injecting messengerRNA (mRNA) nuclease into mouse zygotes (based on theZFN method) was demonstrated in 2010 . The knockout mice were obtained in 2013 using theTALEN technology by injecting TALEN mRNA into thecytoplasm of zygotes . The CRISPR/Cas9 method was also first demonstrated in 2013 ; this method today is the mostpopular in genetic engineering. In this method, targetedgenome editing is carried out due to the complementaryinteraction between the non-coding synthetic RNA and theDNA of the target sites. This forms a complex of non-codingRNAs and Cas proteins which have nuclease activity. Thepigs with a mutation in the genes were obtained by usingthe CRISPR/Cas9 method in the cells of pig embryo at theblastocyst stage in vitro in 2014 .Successful intraspecific neural blastocyst complementationwas performed for the first time in 2018 in mice with \u201cfreeniches\u201d in the brain, including those obtained using theCRISPR/Cas9 method .In order to obtain chimeric animals, ES cells and inducedpluripotent stem cells (iPSCs) are used.ES cells. Pluripotent cells isolated from the inner cellmass(ICM) and epiblast of the embryo are the most suitablecandidates to generate organs in chimeric animals, sincethey are able to differentiate into the embryonic tissue. Itturned out that the pluripotency degree of pluripotent cellsof ICM and epiblast are different in mice. It was proposed tocall \u201ctrue\u201d pluripotent cells obtained from ICM at an earlypluripotency stage \u201cna\u00efve\u201d, and epiblast cells obtained at alater pluripotency stage \u2013 \u201cprimed\u201d . In addition, it turned out that pluripotentcells isolated at the same developmental stage in differentspecies differ in the degree of pluripotency. For example,mouse ES cells isolated from the ICM relate to the \u201cna\u00efve\u201dstatus, while similar human cells relate to the \u201cprimed\u201dstatus of pluripotency.Pluripotent ES cells in the \u201cna\u00efve\u201d status, isolated fromthe ICM of the blastocyst before the implantation stage, areof the most interest for obtaining chimeric animals since itturned out that cells in the \u201cprimed\u201d status are not able totake part in the formation of chimeras when they are injectedinto the preimplantation blastocyst .Mouse ES cells were first obtained in 1981 . Mouse ES cells exhibit typical characteristicsof pluripotency: they have the ability to form cells of ecto dermal, mesodermal, and endodermal origin ,and they are involved in the formation of all tissues of theadult organism, when injected into the blastocyst . And most importantly,mouse ES cells are involved in the formation of chimerasafter injection into the blastocyst .In 1995, ES cells of Rhesus macaque were first obtained. The same researchers obtained human ES cell lines from preimplantation human embryos forthe first time in 1998. The in vivo pluripotency test demonstrated the ability of human ES cells to form teratomas withtissues of endodermal, mesodermal, and exodermal origin. The differentiation of ES cells withthe formation of embryoid bodies and differentiation intovarious cell types was shown in vitro for human ES cells. It is impossible to test for chimerism and to perform an accurate assessment of the pluripotency of human and primate ES cells due to ethical reasons.It appeared that although the human ES cells are similarin a number of characteristics to mouse ES cells , they differ significantlyfrom them . Itis assumed that human ES cells belong to the \u201cprimed\u201d,and mouse ES cells belong to the \u201cna\u00efve\u201d status of pluripotencyPluripotent ES cells of humans and primates in\u201cna\u00efve\u201d status. Human ES cells in \u201cna\u00efve\u201d status were firstobtained in 2010 by the method of ectopic induction of thefactors Oct4, Klf4, and Klf\u200a2 in combination with LIF andthe inhibitors GSK3\u03b2 and ERK1/2 .Then, the cultivation medium and cultivation conditionswere optimized . Attempts have alsobeen made to obtain pluripotent cells in the \u201cna\u00efve\u201d statusin primates . Today, numerous studies are aimed atobtaining pluripotent ES cells in \u201cna\u00efve\u201d status and maintaining this status under culture conditions . Due to ethical reasons, it is not possible to test the \u201cna\u00efve\u201d status of these human pluripotentcells, but it is possible to determine the putative criteria bywhich these cells could be considered pluripotent in \u201cna\u00efve\u201dstatus. Today, the so-called \u201cna\u00efve\u201d factors of pluripotencyare already described. One of these factors is KLF4, whichis specific for mouse \u201cna\u00efve\u201d pluripotent stem cells and forhuman preimplantation embryos . In addition, cells in the\u201cna\u00efve\u201d status are characterized by nuclear localization ofTFE3 and a high level of mitochondrial respiration . Other researchers havedemonstrated that the level of transcription of transposonscorresponds to the status of pluripotency; in addition, theinduction of the \u201cnaive\u201d cell status is accompanied by DNAhypomethylation Obtaining \u201cna\u00efve\u201d status in somatic cells. iPSC. Simultaneously with the study of the \u201cna\u00efve\u201d status of pluripotent ES cells, the technologies for the production of iPSCs fromsomatic cells were actively developing. The iPSCs are a newtype of pluripotent cells that can be obtained by reprogramming differentiated somatic cells. For the first time iPSCsfrom somatic cells were obtained by exogenous expressionof transcription factors in 2006 . The essence of the method is the transfection of anadult cell with four genes ,which encode transcription factors associated with the pluripotent status of embryonic cells. Researchers were able toobtain human iPSC cell lines that meet all the criteria forES cells from human skin fibroblasts and from human skin keratocytes . Since ectopic expression of the c-Myc and Klf4genes is undesirable due to the high risk of forming malignant tumors, these genes were successfully replaced withthe less dangerous genes Nanog and Lin28 in 2007 .The iPSC cells are very similar to ES cells: similar morphology and growth profile, and the same culture conditions. The iPSCs retainthe normal karyotype during cultivation, have high telomerase activity, and differentiate in vitro into tissue cells of allthree germ layers .Capabilities and limitations of using \u201cna\u00efve\u201d ES cellsand iPSCs. The unique properties of ES cells and iPSCsmake it possible to obtain \u201cchimera-competent\u201d cells forblastocyst complementation. When ES and iPSCs areinjected into the blastocyst, these cells are included intodevelopment, leading to the formation of animals with ahigh degree of chimerism. The properties of ES cells andhuman iPSCs make them an exceptional source for obtainingtissues and organs in transplantation and create prospectsfor the development of new approaches for the treatment ofincurable diseases. The technology for generation iPSCs alsodemonstrates the possibilities for generation autologous stemcells, which in the future will allow to solve the problemof immunological compatibility during transplantation oforgans from chimeric animals to a patient. In addition, thistechnology makes it possible to obtain pluripotent stem cellsfrom various types of somatic cells, thus avoiding the ethicalissues associated with the use of living embryos.However, there are some limitations. The cultured ES cellsand iPSCs vary significantly in their pluripotent differentiation potential and gene expression profile .In the population of the obtained ES cells and iPSCs, undifferentiated cells remain which can give rise to a tumor orreactivation of viruses. It also remains a problem to obtain alarge number of \u201cchimera-competent\u201d cells of high qualitysuitable for clinical use. In addition, heritable epigeneticdisorders were found in cultured ES cells, which may beassociated with the development of hereditary diseases andcarcinogenesis . Consequently, thereis a necessity to standardize the condition for obtaining,cultivating, and assessing the pluripotent status of iPSCsand ES cells. Interspecies chimeras of humans and rodents. The availability of \u201cchimera-competent\u201d human cells, generating theanimals with \u201cfree niches\u201d in organogenesis and obtaininginterspecies chimeras of animals by the method of blastocystcomplementation made it possible to make attempts to createchimeric organisms between humans and other animals. In2006 for the first time, human ES cells at the early stages ofembryogenesis were injected into a mouse blastocyst; theobtained chimeras showed developmental abnormalities. In 2013, chimeric mice were obtainedby injecting human iPSCs; however, for ethical reasons, themouse embryos were sacrificed at an early stage of development . Then, in 2014, chimeric animalswere obtained by microinjection of \u201cna\u00efve\u201d iPSCs obtainedfrom Rhesus macaque fibroblasts into a mouse embryo atthe blastocyst stage .However, in the obtained interspecies chimeras, the degreeof revealed chimerism was low, especially in comparisonwith the degree of chimerism in intraspecies chimeras amongrodents. It is speculated that this might be due to the evolutionary distance between humans and other animals. Interestingly, attempts to obtain an interspecies human chimera weresuccessful when human iPSCs were injected into a mouseembryo at a later stage of embryonic development \u2013 at thegastrula stage . Thus, the abilityto form chimeras depends on the coordination of the in vitrodevelopmental stages of donor cells with the in vivo embryodevelopmental stages.Interspecies chimeras of humans and large domesticanimals. In 2017, chimeric embryos were obtained betweena human and a pig, as well as between a human and a cow. In this study, the researchers used CRISPR/Cas9 genetic editing to create a \u201cfree niche\u201d in combinationwith blastocyst complementation. Their results demonstratedthat \u201cna\u00efve\u201d human pluripotent stem cells proliferate inporcine and bovine preimplantation blastocysts, while theirability to proliferate is limited in porcine postimplantationblastocysts. Interestingly, with the use of so-called \u201cintermediate human pluripotent stem cells\u201d, the degree of chimerism and the ability to proliferate into various cell typesin post-implantation pig embryos was higher . Recently, the creation ofa chimeric embryo between Macaca fascicularis and a pigwas reported, functioning donor ES cells of the primate weredetected in the tissues of the pig .The creation of an artificial embryo is a promising alternative to the use of animal and human embryos for researchpurposes. Different researchers have demonstrated thecreation of embryo-like formations on stem cell culture. In 2017, the possibility of creating artificial embryos was demonstrated bythe aggregation of trophoblastic stem cells and totipotentES cells, which independently assemble into a blastocyst on a substrate of a three-dimensional extracellular matrix.Scientists have shown that the development of the embryo,its morphogenesis, structure and cellular composition follow the same development patterns as in a normal embryoThen, in 2018, a fully-fledged blastocyst model was created, which was called the blastoid .Recently, three main types of stem cells have been obtainedfrom fibroblasts: epiblast cells, primitive endoderm cells,and trophectoderm cells. To obtain a certain type of thesepluripotent cells, a combination of five transcription factors was selected: Gata3, Eomes, Tfap2c, Myc, and Esrrb.This achievement could lead to the creation in vitro offully-fledged artificial embryos without the use of an eggand a sperm cell . Advances in thecreation of an artificial embryo demonstrate the possibilityof using it to obtain chimeric organisms in the future.Growing rat organs in a mouse organism and generation ofman-pig, man-cow chimeras give us the possibility of creating xenogeneic organisms among various animal speciesand generating human organs in the future. The candidateanimals for organ transplant growing considered are pigs,cows, sheep, and primates.The development of technology for farming humanorgans in xenogeneic animals such as pigs is hindered bya number of factors. There is a risk of zoonosis and the riskof contamination of human organs with cells or proteins ofthe recipient animal . One problem is that retroviruses integrated into thegenome of chimeric animals can be transferred to humanswhen growing human organs. The consequences of the incorporation of animal retroviruses into the human genomecannot be predicted. There are fears that human organsderived from chimeric animals could be a source of danger.In addition, there are a number of poorly identified andpoorly understood biological factors associated with differences in the rate of embryonic development in differentspecies . Understanding the mechanismsof these differences, the ability to modulate the time anddevelopmental stage of donor cells in vitro, and the abilityto influence the developmental stage in vivo would allowthe synchronization of donor and host cells in a chimericmodel. Recent studies have shown that the synchronizationof developmental stages between donor cultured pluripotentES cells and the recipient is a significant criterion for thesuccessful formation of a chimera. For example, \u201cna\u00efve\u201dmouse ES cells are involved in the formation of a chimeraonly when injected at the blastocyst stage, while \u201cprimed\u201dmouse ES cells isolated from the epiblast are involved in theformation of a chimera when injected at the gastrula stage.It is also interesting that attempts to obtain an interspecieshuman chimera were successful when the injection was carried out at a later stage of embryonic development. Successful microinjection of human iPSCs into a mouse embryo atthe gastrula stage was demonstrated in 2016, which confirmsthe hypothesis that the ability to form chimeras depends onthe coordination of the in vitro stages of donor cells withthe stage of in vivo host embryo development .One of the problems of generating interspecies humanchimeras is the low percentage of donor cells in the chimericorganism. It is assumed that the negative results and lowdegree of chimerism in experiments on generating chimerasare associated with the apoptosis of cells. In 2016, it wasdemonstrated that expression of the anti-apoptotic geneBcl2 in \u201cchimera-incompetent\u201d epiblast stem cells in ratallows these cells to turn into \u201cchimera-competent\u201d cellsand participate in the formation of all tissues in a chimericrat-mouse embryo when injected into a mouse blastocyst.Very recently, it became possible to create human-mousechimeric embryos in which the proportion of human cellsfor the first time was 4 %. In this study, \u00abna\u00efve\u00bb humanPSCs obtained by the inhibition of mTOR protein kinasewere microinjected into mouse blastocysts .Another important problem to be solved for the successfulcultivation of donor human organs in chimeric organisms isthe problem of organ vascularization. Previous studies havedemonstrated that vessels in chimeric organisms are formedfrom the cells of both donor and recipient . For the successful transplantation of human organs grown in animals,it is necessary for the organ\u2019s circulatory system, like theorgan, to be formed from human cells in order to minimizethe xenogenic component during transplantation. Manyresearchers are working on this problem . To solve all these problems,the factors influencing the success of the colonization ofpluripotent donor cells into the organism of the recipientanimal, and the mechanisms underlying the differentiationof these cells in the conditions of the \u201cfree niche\u201d are stillto be determined and investigated.Besides biological, there are also ethical barriers. Forexample, one of the issues that can arise with interspecieshuman-animal chimeras is the production of gametes withthe human genome in chimeric animals . Concerns are also raised by the likelihood of humanization of chimeric animals upon accidentaldifferentiation of human cells in the brain tissues of therecipient . In 2019, it was demonstratedthat these issues can be solved by disabling the Prdm14and Otx2 genes responsible for the formation of gametesand the brain in microinjected \u201cchimera-competent\u201d cells.Thus, in order to carry out successful blastocyst complementation and obtain an interspecies chimera between a humanand another animal for the purpose of growing organs for transplantation, two key technologies need to be improved:(1) creation of animals with \u201cfree niches\u201d, and (2) ethicalgeneration of pluripotent \u201cchimera-competent\u201d humancells capable of differentiating into a target organ or tissuein the body of a host animal. 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DOI 10.1038/emboj.2012.71."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-021-94386-z, published online 22 July 2021Correction to: The original version of this Article contained an error in the spelling of the author Thais Marina Schlee-Guimaraes which was incorrectly given as Thais Schlee-Guimaraes.As a result, the Author Contributions section now reads:\u201cJ.W. performed the experiments. J.W., E.B., and M.S. conceived the experiments and wrote the paper. M.S. secured funding. E.B. and T.Z. provided reagents, expertise and feedback. T.M.S.-G. analyzed 3\u2032 mRNA-sequencing data. All authors revised the manuscript.\u201dThe original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-021-96254-2, published online 18 August 2021Correction to: Aeyeon Kang and Wan S. Yun were omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cThe key idea was conceived by J.H., S.H., A.K., and W.S.Y. J.S. designed the study, performed most experiments, analyzed the data, and wrote the manuscript. H.R.K. aerosolized and collected the virus. P.K.B. prepared the influenza virus solution. H.Y., J.K., and Y.C. wrote the paper. Y.S. prepared the influenza virus solution. J.H. aerosolized and collected the virus. S.H. is responsible for the project and contributed to data analyses. The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript.\u201dThe original Article has been corrected."} +{"text": "Michael J. C. Bray, Bhanu Sharma, Julia Cottrelle, Matthew E. Peters, Mark Bayley, Robin E. A. Green. Hippocampal atrophy is associated with psychotic symptom severity following traumatic brain injury. Brain Communications 2021. doi:10.1093/braincomms/fcab026.In the originally published version of this manuscript, an author\u2019s surname was spelled incorrectly as Cottrelle\u2019s. The correct full name is Julia Cottrelle. This error has been corrected online."} +{"text": "Rhipicephalus turanicus\u2019, Onderstepoort Journal of Veterinary Research 84(1), a1523. https://doi.org/10.4102/ojvr.v84i1.1523, the seventh author, Mbokota C. Khosa, was omitted from the \u2018Authors\u2019 and \u2018Affiliations\u2019 sections. The indicated author should be added as the seventh author, and the following affiliation should be added as his affiliation: Agricultural Research Council \u2013 Tropical and Subtropical Crops, Nelspruit, South Africa.In the published version of this article, Fouche, G., Sakong, B.M., Adenubi, O.T., Dzoyem, J.P., Naidoo, V., Leboho, T. et al., 2017, \u2018Investigation of the acaricidal activity of the acetone and ethanol extracts of 12 South African plants against the adult ticks of The Authors\u2019 contributions section is hereby update to:R. turanicus. K.W.W. wrote the first draft of the manuscript.G.F. conceptualised the study. M.C.K. was involved in the collection of some of the plant material and in the preparation of the extracts used in the biological screening assays. G.F., K.W.W. and T.L. carried out the literature search and plant selection. T.L. prepared the plant extracts. J.N.E. conceptualised the study in a joint application and supervised the students and postdoctoral fellows. V.N. supervised determination of acaricidal activity. J.P.D. supervised the determination of cytotoxicity. B.M.S. determined vero cell toxicity. M.C.K. was also involved in the fractionation and isolation process in the natural product chemistry laboratory. O.T.A. determined the acaricidal activity against adult ticks of"} +{"text": "Agaricomycotina (Basidiomycota) were evaluated to determine synonymy based on their type. Forty-seven sets of sexually and asexually typified names were determined to be congeneric and recommendations are made for which generic name to use. In most cases the principle of priority is followed. However, 16 generic names are recommended for use that do not have priority and thus need to be protected: Aleurocystis over Matula; Armillaria over Acurtis and Rhizomorpha; Asterophora over Ugola; Botryobasidium over Acladium, Allescheriella, Alysidium, Haplotrichum, Physospora, and Sporocephalium; Coprinellus over Ozonium; Coprinopsis over Rhacophyllus; Dendrocollybia over Sclerostilbum and Tilachlidiopsis; Diacanthodes over Bornetina; Echinoporia over Echinodia; Neolentinus over Digitellus; Postia over Ptychogaster; Riopa over Sporotrichum; Scytinostroma over Artocreas, Michenera, and Stereofomes; Tulasnella over Hormomyces; Typhula over Sclerotium; and Wolfiporia over Gemmularia and Pachyma. Nine species names are proposed for protection: Botryobasidium aureum, B. conspersum, B. croceum, B. simile, Pellicularia lembosporum (syn. B. lembosporum), Phanerochaete chrysosporium, Polyporus metamorphosus (syn. Riopa metamorphosa), Polyporus mylittae , and Polyporus ptychogaster (syn. Postia ptychogaster). Two families are proposed for protection: Psathyrellaceae and Typhulaceae. Three new species names and 30 new combinations are established, and one lectotype is designated.With the change to one scientific name for fungal taxa, generic names typified by species with sexual or asexual morph types are being evaluated to determine which names represent the same genus and thus compete for use. In this paper generic names of the International Code of Nomenclature for algae, fungi, and plants , Phanerochaete chrysosporium, Polyporus metamorphosus (Riopa metamorphosa), P. mylittae and P. ptychogaster (Postia ptychogaster) as listed in Table\u00a0Psathyrellaceae over Zerovaemycetaceae and Typhulaceae over Sclerotiaceae as listed in Table\u00a0Forty-seven sets of generic names were identified and evaluated. Details about each set of generic names and the basis for each decision are presented below with an Bulbillomyces, typified by B. farinosus, was described as the sexual morph of A. candida Lyman Aegerita, Donk has been sequenced. Recently Justo et al. (A. candida (as B. farinosus) was sister to the type of Hypochnicium, H. bombycinum. The name Aegerita candida is used about equally with B. farinosus . Aegerita candida is the name used by ecologists who have examined the extracellular enzymatic activity of this aero-aquatic fungus (Abdullah and Taj-Aldeen Crocysporium (GSS 32), is typified by C. aegerita, a name that is considered a synonym of Aegerita candida , was connected to the asexual morph Matula poroniiforme, type of Matula, by Petch , typified by Matula, skipping over description of a family. Fortunately, priority of names only extends to the level of family (Art. 11.1).One final note is that Massee publisheArmillaria is a well-known genus of mushroom-forming fungi lectotypified by A. mellea and is typified by the mushroom-like sexual morph, we here designate Arthrosporella as having priority and recommend Arthrosporella for use.The monotypic generic names n Singer , specifis et al. and Baros et al. . BecauseAsterophora includes species that are parasitic on other mushrooms especially Lactarius and Russula (Russulaceae). Asexual morphs of species of Asterophora have been described in Ugola typified by U. physaroides, a synonym of Asterophora physaroides. Redhead and Seifert C.C. Tu & Kimbr. 1978 (syn. Sclerotium rolfsii Sacc. 1911) is the scientific name for a soilborne pathogen that causes blight stem and root rot diseases of crop and nursery plants throughout the world . Given its priority, greater number of species, and widespread use, the generic name Athelia is recommended for use.The generic name by Donk , include by Donk . Fibularae Rader and is rld Punja . AtheliaGeotrichopsis was introduced for G. mycoparasitica, a hyphomycete that produced thallic-arthric conidia and was isolated as a mycoparasite in a culture of an Arthrobotrys species. Because it had dolipore septa, it was considered to be the asexual state of a basidiomycete (Tzean and Estey Polyporus adustus (now Bjerkandera adusta). However, sequences of the ITS (MH862453) and LSU (MH874100) regions have been obtained from CBS 687.93, the ex-type culture of G. mycoparasitica . In a phylogenetic analysis of the combined ITS and LSU regions of a range of fungi isolated from Prunus, G. mycoparasitica CBS 687.93 fell within a well-supported clade otherwise comprised of B. adusta and B. fumosa, in a subclade with two sequences, one labelled B. adusta and the other B. cf. adusta , and 94.02\u201394.97% to sequences of B. fumosa. The sequence of B. albocinerea MH625420, which has the highest similarity, slightly overlapping with the range of similarity with B. adusta, is shorter, and lacks several characteristic bases that distinguish B. albocinerea from B. adusta. Consequently, Geotrichopsis should be considered a synonym of Bjerkandera and G. mycoparasitica placed in synonymy under B. adusta. Because Geotrichopsis has only been used for one species and is hardly mentioned in the literature , we recommend use of Bjerkandera.z et al. , which iBotryobasidium is typified by B. subcoronatum, while the holotype of Haplotrichum is H. capitatum. Holubov\u00e1-Jechov\u00e1 analysis, Moncalvo et al. , species without asexual morphs and smooth basidiospores (e. g. B. obtusisporum and B. vagum), and species without an asexual morph and ornamented basidiospores (e. g. B. isabellinum) as well as the type B. subcoronatum. These species formed a well-supported monophyletic group as previously demonstrated by micromorphological and ultrastructural characters . In addition, Botryobasidium includes a greater number of names, thus we recommend Botryobasidium for protection.Despite the lack of a known asexual morph of Hibbett and Lars Hibbett , in whico et al. demonstrs Langer . Thus, BBotryobasidium are proposed for protection because they are widely used or already placed in Botrybasidium. In addition, 17 names described in Haplotrichum or other synonymous genera known to belong in Botryobasidium are re-combined in that genus here.Five names in Names proposed for protection:Botryobasidium aureum Parmasto, Eesti N. S. V. Tead. Akad. Toimet., Biol. 14: 220. 1965.Synonyms: Monilia aurea J.F. Gmel., Syst. Nat., Edn 13 2(2): 1487. 1792.Trichoderma dubium Pers., Syn. meth. fung. 1: 233. 1801, nom. sanct. Fr., Syst. Mycol. 3: 216. 1829.Many additional earlier synonyms are listed in Kirk .Botryobasidium conspersum J. Erikss., Symb. Bot. Upsal. 16: 133. 1958.Type: See Table Synonyms to be protected over: Acladium conspersum Link, Ges. Naturf. Freunde Berlin Mag. 3: 11. 1809.Sporotrichum oosporum Ehrenb., Sylv. mycol. berol. 22. 1818.Sporotrichum helvolum Wallr., Fl. crypt. Germ. 2: 280. 1833.Sporotrichum floccosum Bres., Hedwigia 35: 301. 1896.Rhinotrichum olivaceum Bres., Fung. trident. 2(14): 106. 1900.Rhinotrichum bicolor Sumst., Mycologia 3: 50. 1911.Rhinotrichum noblesiae Sumst., Mycologia 29: 250. 1937.Botryobasidium croceum Lentz, Mycopathol. Mycol. Appl. 32: 6. 1967 \u201c1966\u201d.Type: See Table Synonyms to be protected over: Mucor croceus Mont., Ann. Sci. Nat., Bot., s\u00e9r. 2 17: 121. 1842.Gymnosporium fulvum Berk. & M.A. Curtis, J. Linn. Soc., Bot. 10: 355. 1868 \u201c1869\u201d.Rhinotrichum fulvum (Berk. & M.A. Curtis) Berk. & M.A. Curtis, Grevillea 2(19): 108. 1874.Allescheriella uredinioides Henn., Hedwigia 36: 244. 1897.Pellicularia lembospora D.P. Rogers, Farlowia 1: 109. 1943 \u201c1943\u20131944\u201d.Synonyms: Botryobasidium lembosporum (D.P. Rogers) Donk, Fungus 28: 26. 1958.Hymenochaete tomentosa Berk. & M.A. Curtis, J. Linn. Soc., Bot. 10: 335. 1868 \u201c1869\u201d.Botryobasidium simile Hol.-Jech., \u010cesk\u00e1 Mykol. 23: 99. 1969.Synonyms: Oidium simile Berk., J. Bot. (Hooker) 4: 310. 1845.Monilia aureofulva Cooke & Ellis, Grevillea 8(no. 45): 12. 1879.Oidium biforme Linder, Lloydia 5: 188. 1942.Botryobasidium listed above are proposed for protection. This synonymy is based primarily on Partridge et al. G. Langer, comb. nov.MycoBank MB 837648Basionym: Rhinotrichum armeniacum Berk. & M.A. Curtis, Grevillea 3(27): 108. 1875.Botryobasidium caribense (Hol.-Jech.) G. Langer, comb. nov.MycoBank MB 837649Basionym: Oidium caribense Hol.-Jech., Cesk\u00e1 Mykol. 23: 218. 1969.Botryobasidium elongatum (Linder) G. Langer, comb. nov.MycoBank MB 837651Basionym: Oidium elongatum Linder, Lloydia 5: 191. 1942.Botryobasidium gracile (Hol.-Jech.) G. Langer, comb. nov.MycoBank MB 837660Basionym: Haplotrichum gracile Hol.-Jech., Cesk\u00e1 Mykol. 30: 4. 1976.Botryobasidium indicum (P.H. Singh & S.K. Singh) R. Kirschner & G. Langer, comb. nov.MycoBank MB 837873Basionym: Neoacladium indicum P.N. Singh & S.K. Singh, Fungal Diversity 96: 189. 2019.Botryobasidium laevisporum (Cooke) G. Langer, comb. nov.MycoBank MB 837652Basionym: Zygodesmus laevisporus Cooke, Grevillea 6(40): 139. 1878.Botryobasidium magnisporum (Linder) G. Langer, comb. nov.MycoBank MB 837653Basionym: Oidium magnisporum Linder, Lloydia 5: 179. 1942.Botryobasidium morganii (Linder) G. Langer, comb. nov.MycoBank MB 837654Basionym: Oidium morganii Linder, Lloydia 5: 197. 1942.Botryobasidium ovalisporum (Linder) G. Langer, comb. nov.MycoBank MB 837865Basionym: Oidium curtisii var. ovalisporum Linder, Lloydia 5: 204. 1942.Botryobasidium parmastoi (G. Langer) G. Langer, comb. nov.MycoBank MB 837655Basionym: Haplotrichum parmastoi G. Langer, Folia Cryptog. Estonica 33: 63. 1998.Botryobasidium perseae (R.F. Casta\u00f1eda) G. Langer, comb. nov.MycoBan MB 837661Basionym: Haplotrichum perseae R.F. Casta\u00f1eda, Mycotaxon 59: 449. 1996.Botryobasidium pulchrum (Berk.) G. Langer, comb. nov.MycoBank MB 837662Basionym: Rhinotrichum pulchrum Berk., J. Linn. Soc., Bot. 13: 175. 1872 \u201c1873\u201d.Botryobasidium pulveraceum (Ellis) G. Langer, comb. nov.MycoBank MB 837690Basionym: Monilia pulveracea Ellis, Bull. Washburn Coll. Lab. Nat. Hist. 1: 69. 1884.Botryobasidium ramosissimum (Berk. & M.A. Curtis) G. Langer, comb. nov.MycoBank MB 837866Basionym: Rhinotrichum ramosissimum Berk. & M.A. Curtis Grevillea 3(27): 108. 1875.Botryobasidium sphaerosporum (Linder) G. Langer, comb. nov.MycoBank MB 837867Basionym: Oidium sphaerosporum Linder, Lloydia 5: 200. 1942.Botryobasidium tenerum (Sumst.) G. Langer, comb. nov.MycoBank MB 837691Basionym: Rhinotrichum tenerum Sumst., Mycologia 3: 51. 1911.Botryobasidium vesiculosum (Linder) G. Langer, comb. nov.MycoBank MB 837693Basionym: Oidium vesiculosum Linder, Lloydia 5: 193. 1942.Bulleromyces albus, type of the monotypic generic name Bulleromyces, was described as the sexual state of Bullera alba, type of the generic name Bullera . Given that Bullera has priority, currently includes over 60 species, and is widely used, we recommend the use of Bullera.Chaetospermum, typified by C. chaetosporum, the name of the original illegitimate name C. tubercularioides , we recommend the use of Chaetospermum. Bandoni . Kirschn Bandoni noted th Bandoni and Crou Bandoni . In addir et al. who placCoprinellus, lectotypified by C. deliquescens, was resurrected for a segregate group of approximately 50 species previously placed in Coprinus . Given the widespread use of Coprinellus and the many species placed in that genus, it is recommended that Coprinellus be protected.The generic name e et al. demonstrs et al. . In addiOzonium has also been used for a fungus unrelated to O. auricomum, namely the non-sporulating morph of the ascomycete Phymatotrichopsis omnivora (Shear) Hennebert 1973, often listed in the literature as Ozonium omnivorum , Phymatotrichopsis omnivora is an ubiquitous, economically important plant pathogen that causes root rot of alfalfa, cotton, peanut, and pecan as well as diseases of approximately 2000 species of dicotyledonous plants . The synonyms Rhacophyllus lilacinus and Coprinopsis clastophylla are currently both in use at a similar low frequency , and therefore there is no reason not to adopt the earlier name, which we do below. The generic name Hormographiella, typified by H. aspergillata, includes three species each isolated from animals or animal products, including humans . Zerovaemyces was described with a single species, Z. copriniformis, by Gorovij Redhead, comb. nov.Mycobank MB 838345Basionym: Rhacophyllus lilacinus Berk. & Broome, J. Linn. Soc., Bot. 11: 559. 1871.Synonyms: Coprinus clastophyllus Maniotis, Amer. J. Bot. 51: 491. 1964.Coprinopsis clastophylla (Maniotis) Redhead et al., Taxon 50: 227. 2001.Filobasidiella was described by Kwon-Chung . Given its priority, greater number of names, and widespread use, we recommend the use of Dacrymyces.The generic name by Donk based on by Donk and as a by Donk . Ditiolaongniart . This sp Seifert and deteu et al. , 2013, Dand Yang , Shirouzand Yang , 2013, aand Yang demonstrPseudohelicomyces albus, type of the monotypic generic name Pseudohelicomyces, was described for the asexual morph of Psilocybe merdaria while monotypic Pseudohelicomyces remains an obscure name (GSS\u2009=\u200921). Given these reasons and based on priority, we recommend the use of Deconica.Dendrocollybia is typified by D. racemosa, a species previously placed in Collybia . Given the widespread use of Dendrocollybia and its distinct morphology, we recommend that Dendrocollybia be protected over Tilachlidiopsis and Sclerostilbum.The generic name Diacanthodes, typified by D. novoguineensis, includes six species with two varieties of tropical fungi and includes more species than Bornetina (GSS\u2009=\u200970), thus we recommend Diacanthodes for protection.The genus Fidalgo , b, thusCraterocolla, Ditangium and Poroidea was reviewed by Donk , Ditangium has priority and was recommended for use by Malysheva et al. . Because it has a greater number of species and has been used in the recent literature was named by de Hoog from an ex-paratype strain of C. luteoalbus (CBS 208.48) with F. peziziformis. Thus, Cerinosterus and Femsjonia are synonyms. Femsjonia includes 12 names while only two names have been placed in Cerinosterus, one of which, C. cyanescens, is now placed in Quambalaria , we recommend the use of Femsjonia.The genus s McNabb . The put de Hoog as Sporo Maekawa and Midd Maekawa . When Cep. Moore . We confnd Ekman who placFistulina hepatica, type of Fistulina, was described in the monotypic genus Confistulina typified by C. hepatica . Given its priority, greater number of species, and its widespread use, Fistulina is recommended for use.The asexual morph of Acanthellorhiza is typified by A. globulifera, which is the asexual morph of Heteroacanthella acanthophysa . Heteroacanthella has priority and includes three species, while Acanthellorhiza is monotypic and remains little known, thus we recommend the use of Heteroacanthella.The monotypic generic name Roberts . HeteroaHeterobasidion, H. annosum, is the sexual morph of the type of Spiniger, S. meineckellus , while Spiniger includes only one additional species and remains relatively obscure, thus we recommend the use of Heterobasidion.The holotype of Stalpers , thus thHohenbuehelia, typified by H. petaloides, and Nematoctonus, typified by N. tylosporus, was proven by Koziak et al. . Given that Hohenbuehelia has priority and includes 182 names while Nematoctonus includes only 16 names and in agreement with Thorn . According to Else C. Vellinga (pers. comm.), the material examined by Boudier and Patouillard and in agreement with recent authors, we recommend that Marchandiomyces be used.Ghobad-Nejhad et al. demonstr Henrici argued th et al. transferMycena, typified by M. galericulata, is used for over 2000 species of small mushrooms, while the monotypic Decapitatus, typified by D. flavidus based on Stilbum flavidum, was used for the asexual morph of Mycena citricolor . Given the widespread use of Mycena, the high number of species, and its priority, we recommend Mycena for use when Mycena is adopted wth a broad concept.The generic name Myxarium nucleatum, the type of Myxarium, and M. mesonucleatum were shown to form a strongly supported clade with Hyaloria pilacre, type of the generic name Hyaloria, by Kirschner and Chen are similar to those of H. everhartioides suggesting that these names are synonyms or at least closely related. Thus, the available data suggest that Helicomyxa, Hyaloria, and Myxarium are synonyms. Given the greater number of species, greater use , and priority, we recommend the use of Myxarium.and Chen , thus MyNew combinations:Myxarium everhartioides (R. Kirschner & Chee J. Chen) R. Kirschner, comb. nov.MycoBank MB 837868Basionym: Helicomyxa everhartioides R. Kirschner & Chee J. Chen, Stud. Mycol. 50: 339. 2004.Myxarium pilacre (M\u00f6ller) R. Kirschner, comb. nov.MycoBank MB 837869Basionym: Hyaloria pilacre M\u00f6ller, Bot. Mitt. Tropen 8: 173. 1895.Necator decretus was described as a destructive parasite of young coffee branches in Malaysia K.H. Larss., Redhead, & T.W. May, comb. nov.MycoBank MB 838387Basionym: Corticium salmonicolor Berk. & Broome, J. Linn. Soc., Bot. 14(74): 71. 1873 \"1875\".Digitellus humanus, the lectotype of Digitellus, is presumed to be based upon the aborted basidiomes of Neolentinus, most probably N. lepideus . Given its priority, greater number of species, and widespread use, we recommend the use of Oliveonia.The generic name 889 Donk . Althoug Roberts . OliveonPleurotus is applied to a number of mushroom-forming fungi including the type, P. ostreatus, the oyster mushroom, one of the most commonly cultivated edible fungi in the world, and P. eryngii (DC.) Qu\u00e9l. 1872, the widely consumed king oyster mushroom . Considering the widespread use of Pleurotus, its numerous species, its economic importance, and its priority, we recommended the use of Pleurotus.The generic name Labar\u00e8re , thus PlMycelithe, typified by M. fungifera, accommodates sclerotia of Polyporus tuberaster, lectotype of Polyporus. Donk . Given its widespread use and priority as well as the numerous described species, we recommend the use of Polyporus.The monotypic generic name us. Donk providessparrini concludePolyporus. The earliest non-mechanical lectotypification was by Clements and Shear Fr. Epicr. 427 1838\u201d. However, Fries , thus we recommend protection and use of the generic name Postia.chenberg and Shenchenberg , 2019. Wchenberg providedd Hansen and is wd Hansen . Given tn et al. , then PoStalpers . Postia Postia ptychogaster based on Polyporus ptychogaster but neither of these synonyms listed below are widely used. This synonymy has been supported by Shevchenko 3: 424. 1880.Lectotype: See Table Accepted name: Postia ptychogaster (F. Ludw.) Vesterh., Nordic J. Bot. 16: 213. 1996.Rejected synonyms: Ptychogaster albus Corda, Icon. fung.2: 24. 1838.Trichoderma fuliginoides Pers., Syn. meth. fung.1: 231. 1801.Zerovaemyces is regarded as a synonym of Coprinopsis with the type of Zerovaemyces, Z. copriniformis, considered a synonym of Rhacophyllus lilacinus, now Coprinopsis lilacina as discussed above under Coprinopsis. Gorovij is classified in the Psathyrellaceae in modern phylogenetic analyses, thus Zerovaemycetaceae is a synonym of Psathyrellaceae. Psathyrellaceae appears in over 1500 GS records while Zerovaemycetaceae appears in 3 GS hits, two of which are Redhead et al. , thus we recommend the use of Rhizoctonia.The generic name Roberts , thus RhRhizoctonia that belong to Waitea.See below in regard to species of Riopa, previously considered a synonym of Ceriporia, is typified by R. davidii, which is regarded as a synonym of the older name R. metamorphosa by Miettinen et al. Fr. 1832 and thus not available without conservation. Stalpers Miettinen & Spirin, MycoKeys 17: 27. 2016.Basionym: Polyporus metamorphosus Fuckel, Jahrb. Nassauischen Vereins Naturk. 27-28: 87. 1874.Type: see Table Synonyms to be protected over: Mucor aurantius Bull., Hist. Champ. France 1: 103. V. 1791.Sporotrichum aurantiacum Fr., Syst. Mycol. 3: 423. 1832, nom. sanct., non Grev., Mem. Wern. Nat. Hist. Soc. 4: 67. 1822.Michenera, typified by M. artocreas, was described as Licrostroma, typified by L. subgiganteum, by Lemke . Despite its polyphyletic nature, it seems least disruptive to protect the generic name Scytinostroma for the type S. portentosum and its relatives.The sexual morph of by Lemke . Lyman with a new genus Matula, typified by Matula poroniiforme, and not by Artocreas.A final note is that y Massee , was bascf. Donk but are d Curtis first pu. Massee further New combinations:Scytinostroma artocreas (Berk. & M.A. Curtis) K.-H. Larss., comb. nov.MycoBank MB 837870Basionym: Michenera artocreas Berk. & M.A. Curtis, J. Linn. Soc., Bot. 10: 333. 1868 \u201c1869\u201d.Synonyms: Corticium subgiganteum Berk., Grevillea 2(13): 3. 1873.Licrostroma subgiganteum (Berk.) P.A. Lemke, Canad. J. Bot. 42: 763. 1964.Artocreas micheneri Berk. & M.A. Curtis, in Berkeley & Broome, J. Linn. Soc., Bot. 14: 73. 1873 \u201c1875\u201d.Aleurodiscus orientalis Lloyd, Mycol. Writ. 6(62): 927. 1920.Aleurodiscus reflexus Yasuda, Bot. Mag. (Tokyo) 35(420): 269. 1921.Globuliciopsis lindbladii Hjortstam & Ryvarden, Syn. Fungorum 22: 19. 2007.Scytinostroma incrustatum K.H. Larss., comb. nov.MycoBank MB 838392Basionym: Michenera incrustata S.H. He et al., Nova Hedwigia 108: 199. 2018 \u201c2019\u201d.Scytinostroma nodulosum (Rick) K.H. Larss., comb. nov.MycoBank MB 837871Basionym: Stereofomes nodulosus Rick, Egatea 13: 435. 1928.Sistotrema, Fries and includes over 200 names while Ingoldiella includes only three names. Given the widespread use of Sistotrema, the greater number of names, and its priority, we recommend the use of Sistotrema.In sanctioning a, Fries included Webster who obtaSterigmatosporidium polymorphus, the type and only species in Sterigmatosporidium, was described for a species later determined to be the asexual morph of Cuniculitrema polymorpha, the type and only species of Cuniculitrema in their molecular study of Tremellomycetes and placed this species near Fellomyces in Agaricomycotina. Sterigmatosporidium is used more extensively than Cuniculitrema . Given that both genera are monotypic but Sterigmatosporidium has priority and is more widely used, we recommend the use of Sterigmatosporidium.Aegeritina is typified by A. tortuosa, now considered a synonym of Subulicystidium longisporum, the type of Subulicystidium , we recommend the use of Subulicystidium.The monotypic Tomophagus, typified by T. colossus, was established for an unusual species often referred to as Ganoderma colossus (Fr.) C.F. Baker 1920. Hong and Jung , and recent study, we recommend the use of Tomophagus.The generic name and Jung were thee et al. recognizTrechispora, T. onusta, is now regarded as a synonym of T. hymenocystis K.H. Larss. 1995. Ordynets et al. and has priority, while Osteomorpha includes only the type, thus we recommend the use of Trechispora.The type of Larsson . When Wa Larsson validate Liberta . Since t Larsson , althougs et al. showed tTrimorphomyces typified by T. papilionaceus, Kirschner and Chen than Anastomyces (GS\u2009=\u200913). Given its priority and more common use, we recommend the use of Trimorphomyces.In studying and Chen concludeTulasnella is typified by T. lilacina, regarded as a synonym of T. violea by Donk Juel 1897. The synonymy of these two generic names and the selection of Tulasnella as the accepted name by Donk . Similarly, Tulasnella is more widely used than Epulorhiza (GSS\u2009=\u2009875) and the two other obscure generic synonyms . Therefore, we recommend the use of Tulasnella.The generic name by Donk , but not by Donk , b, and Saccardo and BresSaccardo . This waSaccardo . After ty Tubaki and the otiranta , it was otiranta suggest by Donk has neve by Donk and the d Talbot identifio Rogers and Olivo Rogers both of Roberts , b re-exd Talbot was misnz et al. and paper et al. . RegardlEpulorhiza is already considered a taxonomic synonym of Tulasnella and several species, e. g. E. amonilioides and E. anaticula, were already transferred to that genus J. Mack & P. Roberts, comb. nov.MycoBank MB 32427Basionym: Epulorhiza albertensis Currah & Zelmer, Rep. Tottori Mycol. Inst. 30: 48. 1992.Tulasnella calendulina (Zelmer & Currah) J. Mack & P. Roberts, comb. nov.MycoBank MB 832428Basionym: Epulorhiza calendulina Zelmer & Currah, Canad. J. Bot. 73: 1984. 1995.Tulasnella epiphytica J. Mack & P. Roberts, comb. nov.MycoBank MB 832427Basionym: Epulorhiza epiphytica O.L. Pereira et al., Mycoscience 44: 154. 2003.Tulasnella inquilina J. Mack & P. Roberts, comb. nov.MycoBank MB 832430Epulorhiza inquilina Currah et al., Mycotaxon 61: 338. 1997.Basionym: Typhula, lectotypified by T. phacorrhiza Fr. 1838 (syn. Phacorhiza sclerotioides Pers. 1822) was ineffective because this species was not included in the protologue or sanctioning work. The genus Sclerotium, typified by S. complanatum, was established for fungi producing asexual sclerotia. The typification of Sclerotium is explained by Donk , thus we recommend the use of Waitea.The genus Rhizoctonia, typified by R. solani , is not congeneric with W. circinata (syn. Rhizoctonia zeae) J.A. Crouch & Cubeta, comb. nov.MycoBank MB 837872Basionym: Rhizoctonia zeae Voorhees, Phytopathology 24: 1299. 1938.Synonyms: \u201cChrysorhiza zeae\u201d (Voorhees) T.F. Andersen & Stalpers, Rhizoctonia-forming Fungi 58. 1996; nom. inval. (Art. 41.5).Moniliopsis zeae (Voorhees) R.T. Moore, Mycotaxon 29: 96. 1987.Rhizoctonia endophytica var. filicata H.K. Saksena & Vaartaja, Canad. J. Bot. 38: 938. 1960.Waitea circinata var. zeae\u201d Toda et al., Plant Disease 89: 536. 2007; nom. inval. .\u201cRhizoctonia zeae should be placed in Waitea as a species distinct from W. circinata .Diagnosis: Light yellow colony on PDA differs from pinkish-white colonies of W. circinata, white-salmon pink colonies of W. oryzae, yellow-pink colonies of W. prodiga, and orange colonies of W. zeae. Irregularly shaped, dark brown sclerotia differ from pinkish or orange sclerotia of W. circinata, irregular, salmon-pink to orange sclerotia of W. oryzae, irregular to spherical salmon to yellow-salmon sclerotia of W. prodiga, and the subspheroid, orange sclerotia of W. zeae.Description: Toda et al., J. Gen. Plant Path.73: 385. 2007.Type: Illustration in J. Gen. Plant Path. 73: 383, fig. 1, 2007 (holotype) based on an unspecified collection made in Japan. Representative sequence: GenBank AB213567 (ITS) derived from a collection: Japan, Aichi, on Agrostis stolonifera L. var. palustris, June 1999, isolate NUK-3BG (deposition unknown).Rhizoctonia sp. was found causing a destructive new disease affecting Agrostis stolonifera and Poa pratensis turfgrasses in Japan; the disease is referred to as Waitea reddish-brown patch disease .Waitea circinata var. oryzae\u201d Toda et al., Plant Disease 89: 536. 2007; nom. inval. .\u201cDiagnosis: White to salmon pink colony on PDA differs from pale yellow colonies of W. agrostidis, pinkish-white colony of W. circinata, yellowish pink colony of W. prodiga, and orange colony of W. zeae. Irregularly shaped, salmon-pink to orange sclerotia differ from irregular, dark brown sclerotia of W. agrostidis, pinkish or orange sclerotia of W. circinata, irregular to spherical, salmon to yellow-salmon sclerotia of W. prodiga, and subspheroid, orange sclerotia of W. zeae.Description: Ryker & Gooch, Phytopathology 28: 238. 1938; as \u201cRhizoctonia oryzae\u201d.Type: USA: Louisiana: Crowley: on stems of Oryza sativa, 22 Jul. 1938, T.C. Ryker 3049 (BPI 455795 \u2013 holotype). Representative sequence: GenBank AB213589 (ITS) derived from a collection: Japan, Toyama, on Oryza sativa, isolate RoTTS (deposition unknown).Rhizoctonia oryzae and W. circinata var. oryzae are invalid names used by plant pathologists to refer to the causal agent of leaf and sheath spots of grasses and cereals. Although neither of these two names were validly published, there is no doubt that this fungus is congeneric with W. circinata and distinct from other species in the genus .Diagnosis: Yellow-pink colony on PDA differs from pale yellow colony of W. agrostidis, dark brown colony of W. circinata, white-salmon pink colony of W. oryzae, and orange colony of W. zeae. Irregular to spherical, salmon to yellowish salmon sclerotia differ from irregular, dark brown sclerotia of W. agrostidis, pinkish or orange sclerotia of W. circinata, irregular, salmon pink to orange sclerotia of W. oryzae, and subspheroid, orange sclerotia of W. zeae.Description: Kammerer et al., Plant Disease95: 521. 2011.Type: Illustration in Plant Disease 95: 517, fig. 2a, 2b (second sclerotium from left), 2011 (holotype), based on the collection: USA: Florida: Fort Myers, on leaves of Paspalum vaginatum \u2018Sea Dwarf\u2019, 4 Jan. 2008, S.J. Kammerer 44 SK-PSA-TM4 (ITS GenBank HM597146).Waitea circinata var. prodiga was proposed as the name of a novel fungal pathogen responsible for a basal rot disease first identified from Paspalum vaginatum relate to currently accepted species, while Pachyma tuber-regium is the sclerotial state of Pleurotus tuber-regium and Pachyma woermannii was introduced for the sclerotium of Lentinus woermannii, which is considered by Pegler (Pleurotus tuber-regium (as Lentinus tuber-regium). Wolfiporia is more widely used than Pachyma and the other names remain obscure. More recently, the entire genome of Wolfiporia cocos was sequenced and all sequences deposited under this name Y.-C. Dai & V. Papp, comb. nov.Basionym: Pachyma hoelen Fr., Syst. Mycol. (Index): 125. 1832, nom. sanct.MycoBank MB 838346Type: See Table Phanerochaete chrysosporium is widely known for its industrial use as a white rot fungus that breaks down the aromatic polymer lignin and thus is important in the degradation of wood products N\u00fa\u00f1ez & Ryvarden based on P. mylittae. This species produces large sporophores after wildfires and has been frequently recorded from across Australia as both Polyporus and Laccocephalum, under the epithet mylittae, including as a target species for the Fungimap mapping scheme Pat., but there is no such obstacle to the transfer of M. australis to Laccocephalum. However, the name M. australis has only ever been applied to the sclerotium, and little used since the discovery of the sporophores more than a century ago. Therefore, P. mylittae is proposed for protection over M. australis to allow the continued use of L. mylittae.The genus Berkeley for the ae Cooke . The cons\u2019 Cooke . All subs\u2019 Cooke have accRyvarden expanded"} +{"text": "Geosesarma (Sesarmidae) is described from a limestone cave in central Sarawak, Malaysian Borneo. Geosesarmasodalissp. nov. is characterised by its quadrate carapace, absence of a flagellum on the exopod of the third maxilliped, presence of 10 or 11 sharp tubercles on the dactylus of the chela and a diagnostic male first gonopod structure. This is the sixth species of Geosesarma reported from Sarawak, and the first member of the genus collected from inside caves.A new species of semi-terrestrial crab of the genus Arachnothelphusa Ng, 1991, by In 2005, Rob Stuebing passed the author several brachyuran crabs he collected while surveying limestone caves in the Bintulu area in central Sarawak. The material included a new species of a cavernicolous gecarcinucid, and in 2006, fresh surveys were made in the caves to obtain more specimens. This new material formed the basis for the description of a new species of Geosesarma De Man, 1892 (Sesarmidae). Examination of the specimen showed it to be a new species, here named Geosesarmasodalis sp. nov. This is also the first record of a Geosesarma from inside caves. Geosesarma are often called vampire crabs because many species have bright yellow eyes in life of the Lee Kong Chian Natural History Museum, National University of Singapore.Measurements provided are the carapace width and length. The terminology used in this paper follows Taxon classificationAnimaliaDecapodaSesarmidaeGenusDe Man, 1892A145B6CF-9696-57B9-8F7E-EDDB72E402FBSesarma (Geosesarma) nodulifera De Man, 1892; subsequent designation by Taxon classificationAnimaliaDecapodaSesarmidae62B0437F-0230-5D64-A5CD-428E177663A1http://zoobank.org/69A4BE4D-8B0B-4243-9B2D-BA1D559A2C28Holotype: male (10.1 \u00d7 9.8 mm) (ZRC 2020.0413), limestone cave, Bukit Sarang, Bintulu, Sarawak, Malaysia, coll. Stuebing RB, early 2005.G1 relatively slender, proximal, distal part bent at angle of ca. 45\u00b0 along longitudinal axis, subdistal part of outer margin gently angular with shelf-like feature . In Borneo, the species in this group are G.gracillimum , G.sabanus Ng, 1992, G.aurantium Ng, 1995, G.katibas Ng, 1995, G.danumense Ng, 2002, G.bau Ng & Grinang, 2004, G.ambawang Ng, 2015, G.pontianak Ng, 2015, G.larsi Ng & Grinang, 2018, and G.spectrum Ng & Ng, 2019.The island of Borneo has 13 known species of Sarawak . One groG.gracillimum, G.katibas, G.bau, G.larsi, and G.sodalis sp. nov. Compared to G.gracillimum, the carapace of G.sodalis sp. nov. is more quadrate with the lateral margins subparallel .Five of the species in this group are present in Sarawak and Brunei: lel Fig. and the outer surface of the chela with fewer small granules in ov. Fig. , differ ules see : fig. 1Cov. Fig. is similibas see : fig. 8Dibas see .G1 differences between G.sodalis sp. nov. and G.spectrum (from Brunei) are the same as for the Sarawakian G.katibas. Geosesarmasodalis sp. nov. differs markedly from the two species in this group from Indonesian Kalimantan, G.ambawang and G.pontianak, in possessing a G1 that is proportionately stouter and the subdistal part of the outer margin has a prominent right angled hump-like arch . Although more surveys in and around the Bukit Sarang were conducted in 2006 and more specimens of A.sarang were collected and K.malang Wowor & Ng, 2018) are close to Geosesarma. Until the present discovery of G.sodalis sp. nov., no species of Geosesarma has previously been found in caves. Geosesarmasodalis sp. nov., however, has none of the morphological features associated with a cavernicolous lifestyle, e.g., reduced eyes and/or cornea and elongated pereopods. In any case, G.sodalis sp. nov. differs markedly from the group of Karstarma species highlighted by G1, as well as its well-developed eyes with the large pigmented cornea.No cies see ; Ng 2020Pseudosesarmabrehieri Ng, 2018, is now known to normally live in mangrove habitats (Another species of sesarmid which was originally desrribed from near the entrance of a cave in Myanmar, habitats ."} +{"text": "The authors wish to make the following erratum to this paper :The published version of The list of authors was incorrect and did not accurately reflect the contributions of individuals that contributed to the overall work. It is changed to:1,*, Stephanie J. Spada 2, Vanessa M. Hirsch 2 and Fadila Bouamr 2Kevin M. Rose 1 Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California\u2014Berkeley, Berkeley, CA 94720, USA2 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Rockville, MD 20894, USA; stephanie.spada@nih.gov (S.J.S.); vhirsch@niaid.nih.gov (V.M.H.); bouamrf@mail.nih.gov (F.B.)kevin_rose@berkeley.edu* Correspondence: The Author Contribution section was changed to: S.J.S. conceptualized nuclear envelope mechanisms. F.B. co-wrote the manuscript. K.M.R., V.M.H.\u2013writing. All authors have read and agreed to the published version of the manuscript.The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "Scientific Reports 10.1038/s41598-020-74650-4, published online 22 October 2020Correction to: Ivan P. Moskowitz was omitted from the author list in the original version of this Article.The Author Contributions section now reads:\u201cC.E.T., A.M.H., M.E.Z., S.L.S., M.P.E., D.J.C., and J.G.M. were all involved in the conception and design of the work presented in this manuscript. C.E.T. and A.M.H. jointly drafted the manuscript, with all authors reviewing and providing feedback on the manuscript. Ascertainment of the samples and phenotype assessment of individuals with DS were accomplished through the efforts of S.L.S., C.L.M., T.C.R., K.J.D., G.T.C., R.H.R, P.J.G., J.E.O., D.C.B., L.W., C.L.C., I.P.M., and E.G. (sponsor of PCGC-approved ancillary project). H.R.J., D.J.C., and B.L.R. performed mapping and variant calling for the WES and WGS datasets, and together with C.E.T. performed QC of these data. C.E.T. performed the gene- and pathway-level (SKAT) analyses. H.C. and J.O. were involved in the initial phase of these datasets and helped to set the framework for these analyses. H.J.C., B.D.K., A.J.A., and E.G. generated the GWAS summary results used as training data for the PRS analyses. A.M.H. performed imputation of the array genotype data, and QC and analyses for the PRS application.\u201dThe Acknowledgements section now reads:https://benchtobassinet.com). Support for the PCGC is provided through grants from National Heart, Lung, and Blood Institute . We would like to thank Marianne S. Hird at the PCGC for her help on this project throughout its administration. The Agopian et al. (2017) GWAS discovery dataset used for the PRS analyses was generated with support from an Institutional Development Fund to The Center for Applied Genomics from The Children\u2019s Hospital of Philadelphia. Further support was provided by the National Heart, Lung, and Blood Institute P50-HL74731 (E.G.) and the National Center for Research Resources M01-RR-000240, RR024134 [now the National Center for Advancing Translational Sciences UL1TR000003) (E.G.). The Cordell et al. (2013) GWAS discovery data used for the PRS analyses were generated with support from the British Heart Foundation, Heart Research UK, Wellcome Trust and European Union. B.D.K. is supported by a British Heart Foundation Personal Chair. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.\u201d\u201cFirst and foremost, we want to thank the families and individuals with Down syndrome for contributing their time and effort towards this project. The DS Heart Project (R.H.R.) was a collaborative project supported through several National Institutes of Health awards: R01 HL092981-01A1 (M.E.Z.) and R01 HL083300 (R.H.R.) from NIH/National Heart, Lung, and Blood Institute; R01 HD38979 (S.L.S.) from NIH/National Institute of Child Health and Human Development and GM117946 (M.P.E.) from NIH/National Institute of General Medical Sciences. Whole exome sequencing services that were done as part of the DSHP were provided by the University of Washington, Department of Genome Sciences under U.S. Federal Government contract number HHSN268201100037C (D. Nickerson). Whole genome sequencing services were supported by the Emory Integrated Genomics Core (EIGC) and the Emory Integrated Computational Core (EICC), which are subsidized by the Emory University School of Medicine and are part of the Emory Integrated Core Facilities. Partial support to M.E.Z was also provided by the Georgia Clinical & Translational Science Alliance which is funded by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award number UL1TR002378. The American Heart Association Western States Affiliate provided support to H. Corbitt (grant number 16PRE30190012). I.P. Moskowitz was supported by the following grants: R01 HL092153, R01 HL124836, and R01 HL126509. We thank Dr. Eleanor Feingold for providing the chromosome 21 genotype calls for the SNP Affymetrix dataset. We thank the Pediatric Cardiac Genomic Consortium (PCGC) for its contributions to this work, and recognize E.G. as sponsor of the PCGC-approved ancillary project. The PCGC provided samples for the WGS study which were collected under the auspices of the National Heart, Lung, and Blood Institute\u2019s Bench to Bassinet Program (The original Article and accompanying Supplementary Information file have been corrected."} +{"text": "We present handheld optical coherence tomography (OCT) diagnosis of Grade 4 foveal hypoplasia (fovea plana) in a 28-day-old infant with albinism. Grade 4 foveal hypoplasia is characterized by the absence of the foveal pit, absence of outer segment lengthening, and absence of outer nuclear layer widening. Binocular visual acuity at 58 months follow-up was 1.2 logarithm of the minimal angle of resolution (logMAR). We describe our handheld OCT acquisition protocol and compare the morphological features with a healthy, age-matched control subject. In this article, we present optical coherence tomography (OCT) imaging obtained from a 28-day-old Caucasian male patient with albinism, referred to our clinic for workup of infantile nystagmus. On examination, the patient had pendular nystagmus, transillumination defects, and cutaneous hypopigmentation. The patient was unable to cooperate with preferential looking testing.Figure Albinism is associated with nystagmus and foveal hypoplasia \u20133. TypicPredicting future VA using OCT can help parents in planning adjustments to optimize their child's development and educational attainment . From thSTATEMENT OF AUTHORSHIPCategory 1: a. Conception and design: S. R. Rufai, H. Lee, and I. Gottlob; b. Acquisition of data: S. R. Rufai, H. Lee, and I. Gottlob; c. Analysis and interpretation of data: S. R. Rufai, H. Lee, and I. Gottlob. Category 2: a. Drafting the manuscript: S. R. Rufai; b. Revising it for intellectual content: H. Lee and I. Gottlob. Category 3: a. Final approval of the completed manuscript: S. R. Rufai, H. Lee, and I. Gottlob."} +{"text": "Adv. Sci. 2021, 8, 200207310.1002/advs.202002073DOI: In the originally published article, one funding information is missing in the acknowledgments. Please find the correct acknowledgements here:"} +{"text": "Surgical site infection (SSI) is the most common and costly complication of surgery. International guidelines recommend topical alcoholic chlorhexidine (CHX) before surgery. However, upper limb surgeons continue to use other antiseptics, citing a lack of applicable evidence, and concerns related to open wounds and tourniquets. This study aimed to evaluate the safety and effectiveness of different topical antiseptics before upper limb surgery.This international multicentre prospective cohort study recruited consecutive adults and children who underwent surgery distal to the shoulder joint. The intervention was use of CHX or povidone\u2013iodine (PVI) antiseptics in either aqueous or alcoholic form. The primary outcome was SSI within 90 days. Mixed-effects time-to-event models were used to estimate the risk (hazard ratio (HR)) of SSI for patients undergoing elective and emergency upper limb surgery.A total of 2454 patients were included. The overall risk of SSI was 3.5 per cent. For elective upper limb surgery (1018 patients), alcoholic CHX appeared to be the most effective antiseptic, reducing the risk of SSI by 70 per cent , when compared with aqueous PVI. Concerning emergency upper limb surgery (1436 patients), aqueous PVI appeared to be the least effective antiseptic for preventing SSI; however, there was uncertainty in the estimates. No adverse events were reported.The findings align with the global evidence base and international guidance, suggesting that alcoholic CHX should be used for skin antisepsis before clean (elective upper limb) surgery. For emergency (contaminated or dirty) upper limb surgery, the findings of this study were unclear and contradict the available evidence, concluding that further research is necessary. This international study recruited 2454 children and adults undergoing surgery on their upper limb (arm or hand), from 42 hospitals worldwide. The overall risk of infection after surgery was 3.5 per cent. Before planned (elective) surgery, if surgeons cleaned the skin with alcoholic chlorhexidine, then the risk of infection was reduced by 70 per cent. CIPHUR was advertised and collaborators were recruited via the UK\u2019s Reconstructive Surgery Trials Network (RSTN), the Clinical Trials Network of Australia and New Zealand (CTANZ) and the Australasian Clinical Trials in Plastic, Reconstructive & Aesthetic Surgery (ACTPRAS) collaboratives. The study was registered at each participating hospital in accordance with local and national regulations. Informed consent was taken from patients if required by local or national regulations. In the UK, CIPHUR was registered as a service evaluation approval was not required as per the HRA decision tool) and collaborators were required to provide evidence of Caldicott Guardian approval before being registered. In Australia, the project was formally reviewed by the Townsville and Cairns Human Research Ethics Committees and defined as a quality assurance project, and thus exempt from ethical review. No changes were made to patients\u2019 usual care in the conduct of CIPHUR. Routine, anonymized data were captured via the Research Electronic Data Capture (REDCap) web applicationConsecutive adults and children undergoing surgery (elective or emergency) distal to the shoulder joint were eligible. Patients with any active infection (anywhere in the body) at the time of surgery were excluded. Active infection was defined pragmatically as either a suspicion of infection or the provision of any medical or surgical treatment for either suspected or confirmed infection.Any hospital offering upper limb surgery, in any location or setting, was eligible to participate. Collaborators were required to enrol consecutive patients (to mitigate selection biases) during the recruitment phase from 1st March 2020 to 31st December 2020 .Of the 2454 records submitted, 2294 (94 per cent) contained all data required to model the primary outcome and were thus considered to be 100 per cent complete. The primary outcome (SSI) was missing completely at random in 31 records (1 per cent). The overall rate of missing data was 4.1 per cent for the minimum data set required to model the primary outcome. Therefore, multiple imputations were not performed, and complete case analysis proceeded withhttps://osf.io/v6k8u/). Continuous variables which approximated the normal are presented as the arithmetic mean(s.d.) and compared using linear methods. Skewed continuous variables are summarized as the median with interquartile range (i.q.r.) and compared using the Mann\u2013Whitney U test. Categorical variables are presented as frequencies with percentages and compared using the Fisher\u2019s exact test.The raw data and REDCap data dictionary are available via the Open Science Framework were used for emergency and elective surgery patients separately. The categorical fixed-effects common-to-both models were antiseptic, diabetes, current tobacco smoking, wound toilet at assessment, preoperative antibiotics, grade of the operating surgeon, method of wound closure, and postoperative antibiotics. For emergency surgery, CDC wound status (level of contamination) and wound toilet were added as categorical covariables, and hours from injury to surgery as a continuous covariable. We planned to use ageas a covariable but decided to remove this factor, as the coefficient was effectively zero. The hospital , compared with elective surgery . The median time to diagnosis of SSI was 15 (i.q.r. 7\u201328) days.Overall, 2454 patients were included. Baseline demographics are presented in Alcoholic CHX was superior to all other antiseptics for elective surgery (1018 patients) (versus non-absorbable sutures) were not associated with the risk of SSI.After adjustment, no other factors were associated with SSI . This suggests that geography has little effect on the risk of SSI in emergency surgery. Overall, despite the uncertainty, the data suggest that aqueous PVI is the least effective antiseptic for preventing SSI following emergency upper limb surgery.The least effective antiseptic for preventing SSI in emergency upper limb surgery (1436 patients) was aqueous PVI (versus non-absorbable sutures).For emergency surgery only, after adjustment, smokers had more than twice the risk of SSI, compared with non-smokers , although an important minority were readmitted for a median of 3 days. Most patients were treated with oral antibiotics alone . Fourteen patients (17 per cent) underwent revisional surgery. Twelve patients were readmitted for intravenous antibiotics (15 per cent), and most were subsequently discharged with oral antibiotics.The weighted cost of unplanned admission for SSI was \u00a3996.76 for an admission of 2 days or shorter, and \u00a33926.16 for a longer admission was multiplied by the weighted average cost of additional inpatient days (\u00a3341.14) . Various other microbes were also isolated, including different species of Streptococcus (three patients), Staphylococcus (four patients), Pseudomonas (one patient), Proteus (one patient), and Enterobacter (one patient). Three patients had no growth on cultures and one patient had \u2018skin flora\u2019 isolated.In 23 patients, samples were taken for microbiological analysis. The most prevalent pathogen in patients with SSI was No serious adverse events were reported; specifically, there were no ignition fires or chemical burns beneath tourniquets. Four patients (0.2 per cent) reportedly developed a skin \u2018rash\u2019 after being exposed to alcoholic PVI (two patients) and alcoholic CHX (two patients).,This international multicentre, prospective cohort study supports the findings of meta-analyses on cleanDue to the scale of hand surgery performed worldwide, even a small reduction in risk of SSI at the population level is likely to translate to considerable benefits for patients and healthcare services alike. Although the evidence remains unclear for emergency upper limb surgery, this study demonstrates that swapping to preoperative alcoholic CHX skin antisepsis for elective upper limb surgery may be associated with a 70 per cent reduction in risk of SSI, with no additional risk. For example, the NHS commissioned over 123 301 operations for four common hand conditions during 2020,,,,,This study provides data to challenge dogma in several areas of upper limb surgery. First, the provision of preoperative antibiotics was not associated with a reduced risk of SSI in either the elective or emergency surgery models. This is in keeping with the wider literature on perioperative antibiotic use in upper limb surgeryThere were no serious adverse events related to antiseptic use in this study, which is in keeping with the literatureMissing data are ubiquitous in clinical research. Although reasonable steps were taken to acquire missing data (by contacting collaborators), a small proportion of required data was still missing and consequently, the final model might not be representative, standard errors may be inflated, and potentially valuable data might have been discarded. Equally, there may be confounding factors which were not captured, and heterogeneity of patients, antiseptics , and it should therefore be avoided. The limited The findings of this study align with the global evidence base and international guidance regarding clean surgery, suggesting that alcoholic CHX should be used for skin antisepsis before clean (elective upper limb) surgery. For emergency (contaminated or dirty) upper limb surgery, the findings of this study were unclear and contradict the available evidence, suggesting that further research is necessary.R. Bindra , M. Sher , M. Thomas , S. D. J. Morgan , B. Hwang , W. Santucci , P. Tran , L. Kopp , V. Kunc , A. Hamdi , P. P. Grieve , S. A. Mukhaizeem , K. Blake , C. Cuggy , R. Dolan , E. Downes , E. Geary , A. Ghadge , P. Gorman , M. Jonson , N. Jumper , S. Kelly , L. Leddy , M. E. McMahon , C. McNamee , P. Miller , B. Murphy , L. O'Halloran , K. O\u2019Shea , J. Skeens , S. Staunton , F. Timon , J. Woods , U. Cortinovis , L. Sala , V. Zingarello , M. H. Jusoh , A. N. Sadagatullah , G. Georgieva , S. Pejkova , B. Nikolovska , B. Srbov , H. K. S. Hamid , M. Mustafa , M. Abdelrahman , S. M. M. Amin , D. Bhatti , K. M. A. Rahman , I. Jumabhoy , J. Kiely , I. Kieran , A. C. Q. Lo , K. Y. Wong , A. Y. Allan , H. Armes , M. D. Horwitz , L. Ioannidi , G. Masterton , H. Chu , G. D. Talawadekar , K. S. Tong , M. Chan , M. Tredgett , C. Hardie , E. Powell-Smith , N. Gilham , M. Prokopenko , R. Ahmad , J. Davies , S. Zhen , D. Dargan , R. M. Pinder , M. Koziara , R. Martin , E. Reay , E. Cochrane , A. Elbatawy , F. Green , T. Griffiths , G. Higginbotham , S. Louette , G. McCauley , I. Natalwala , E. Salt , R. Ahmed , P. Goon , R. Manton , N. Segaren , G. Cheung , R. Mahoney , S. Sen , D. Clarkson , M. Collins , A. Bolt , P. Lokanathan , A. Ng , G. Jones , J. W. M. Jones , R. Kabariti , S. J. Rhee , J. Herron , A. Kay , L. K. Cheung , D. Thomson , R. S. Jugdey , H. Yoon , Z. L. , J. Southgate , C. Brennan , S. Kiani , M. Zabaglo , Z. A. Haider , R. Poulter , A. Sheik-Ali , A. Watts , B. Jemec , N. Redgrave , L. Dupley , M. Greenhalgh , J. Vella , H. Harris , A. V. Robinson , S. Dupre , S. Teelucksingh , A. Gargan , S. Hettiaratchy , A. Jain , R. Kwasnicki , A. Lee , M. Thakkar , D. Berwick , N. Ismail , M. Mahdi , J. Rodrigues , C. Liew , A. Saadya , M. Clarkson , C. Brady , R. Harrison , A. Rayner , G. Nolan , B. Phillips , N. Madhusudan .R.G.W. is a Doctoral Research Fellow funded by the National Institute for Health Research (NIHR) (DRF-2018\u201311-ST2-028). J.P.T. is a Clinical Lecturer funded by Health Education England (HEE)/NIHR. J.C.R.W. is a Research Fellow funded by the Royal College of Surgeons of England and the British Society of Surgery for the Hand. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS, or the UK Department of Health and Social Care.zrab117_Supplementary_DataClick here for additional data file."} +{"text": "Neutralizing antibodies in the subjects of an inactivated SARS-CoV-2 vaccine clinical trial showed a decreasing trend over months. An investigation studying the third immunization suggested that the waning of neutralizing antibodies in individuals administered two doses of inactivated vaccine does not mean the disappearance of immunity. Thenjection c, d. Hownjection c, d. ELInjection c, d. Thenjection c, d. Thenjection g and sugnjection e, f; S anjection e, f. Intnjection g. Furthenjection h. Of the"} +{"text": "Scientific Reports 10.1038/s41598-021-97778-3, published online 20 September 2021Correction to: The original version of this Article contained errors.Some of the figure panels have been manipulated to remove the features irrelevant to the scientific content depicted in those . The Authors recognise that this level of manipulation was inappropriate, and provide original images. As a result, the following panels were corrected and the original versions of the figures containing these panels are shown below for the record: Figure Additionally, scales were re-adjusted in the following panels: Figure Finally, panel Original versions of all affected figures are reproduced below for the record.Additionally, a further clarification of how the OxCal tool was used are now included in the paper. A new subsection called \u2018Bayesian analyses of radiocarbon dates\u2019 was added at the end of the Methods section. This subsection includes two new references, References 203 and 204, which are now added to the Reference list in the published Article:204. The \u2018Combine\u2019 function is used to combine two or more radiocarbon dates from different sources that are believed to be coeval, e.g., the date that beams were used to build a cathedral204. The \u2018Combine\u2019 routine is the one used in Bunch et al., because there were different radiocarbon sources, e.g., charred palace beams and charred seeds. The presence of tens of thousands of pieces of charcoal, wood, melted mudbricks, melted pottery, and melted spherules randomly mixed throughout a single unstratified, unconsolidated stratum strongly supports the hypothesis that they represent a single city-wide episode of biomass burning. Thus, the \u2018Combine\u2019 function is the appropriate OxCal routine to use.\u201d\u201cThere are two functions in OxCal that are used for combining dates from a single inferred event. The \u2018R_Combine\u2019 function is used to combine two or more radiocarbon dates from the same source, e.g., a single skeletonThe Competing Interests section was updated and now reads:\u201cT.E.B., M.A.L., J.H.W., W.S.W., G.H., C.R.M., J.P.K., and A.W. volunteer their time as cofounders and/or directors of the Comet Research Group (CRG), a 501(c)(3) nonprofit organization. CRG received donations from the public and contributed funding for equipment, supplies, and scientific analyses. T.E.B., M.A.L., J.H.W., W.S.W., G.H., C.R.M., J.P.K., and A.W. receive no salaries, compensation, stock, or any other financial benefits from CRG, except that M.A.L., G.H., and A.W. realize tax benefits from donations to CRG. In some cases, co-authors have been compensated for out-of-pocket expenses, such as airfare, that are directly related to the TeH research.P.J.S. volunteers his time and receives no salary from Trinity Southwest University (TSU), a 501(c)(3) nonprofit organization. TSU received donations and contributed support, supplies, equipment, and funding for TeH Excavation Project. P.J.S. was reimbursed by Trinity Southwest University for his hotel room while in Jordan but not for other out-of-pocket expenses.P.J.S. is the author of two books related to TeH.A.W. is the author of a book unrelated to TeH.A.V.A., C.M., D.B., E.C.S., G.K., J.K., K.L., M.C.L.P., R.E.H., S.M., T.D.B., and T.W. received salaries, supplies, equipment, and/or funding for scientific analyses from their respective universities/organizations, which, due to the worldwide publicity, possibly stand to benefit from increased donations and student enrollments.All co-authors have not yet but may receive reimbursements for attending symposia on this research from their respective organizations. All co-authors were involved in various aspects of conceptualization, design, data collection, analysis, the decision to publish, and/or preparation of the manuscript.\u201dFinally, the beginning of the Acknowledgements section was updated,\u201cWe gratefully acknowledge the invaluable assistance of the senior staff at Tall el-Hammam: Director, Steven Collins; Assistant Director, Gary A. Byers, and Assistant Director, Carrol M. Kobs.\u201dnow reads:\u201cWe gratefully acknowledge the invaluable assistance of the senior staff at Tall el-Hammam: Director, Steven Collins; Assistant Director, Gary A. Byers, and Assistant Director, Carrol M. Kobs. Additionally, we thank Daniel Galassini, Michael Luddeni, Brandy Forrest, James Barber, and Sultan Madi, who took the site excavation photographs for the Tall el-Hammam Excavation Project, which made them available for this study .\u201dThe original Article has been corrected."} +{"text": "The impact of preexisting neurodegenerative diseases on superimposed SARS\u2010CoV\u20102 infections remains controversial. Here we examined the course and outcome of SARS\u2010CoV\u20102 infections in patients affected by Parkinson's disease (PD) or dementia compared to matched controls without neurodegenerative diseases in the LEOSS (Lean European Open Survey on SARS\u2010CoV\u20102\u2010infected patients) cohort, a large\u2010scale prospective multicenter cohort study.The LEOSS scientific data set comprises anonymous data after data quality control, including plausibility checks. Collected data include demographic information, standardized clinical classification of the SARS\u2010CoV\u20102 severity , administered medical care , preexisting and concomitant signs and symptoms, medication, laboratory parameters, and mortality. The patient sample age is grouped in decades.Our study population comprised n = 4310 SARS\u2010CoV\u20102\u2010infected patients (59% men). Forty of them had PD ; 290 had dementia and 2 randomly selected controls for each dementia patient (1:2). Any potentially confounding effects resulting from variability in age and sex were fully adjusted for by the matching procedure. To avoid bias, we handled patients and controls the same way according to standard epidemiological principles.The overall SARS\u2010CoV\u20102\u2010associated mortality in the PD (32.5%) and dementia (32.1%) groups did not significantly differ from their respective control groups (28.7% and 26.5%).Delirium occurred more frequently in dementia compared to PD and controls, but patient\u2010reported parameters were less frequent in dementia compared to PD and controls. Interestingly, dementia patients remained in the ICU and were ventilated for a shorter time period than controls. The major SARS\u2010CoV\u20102 outcome parameters were also not significantly different between PD patients, dementia patients, and controls. The age and gender distributions in our patient sample were not significantly different from previously published epidemiological cohort studies reporting the typical characteristics of German PD and dementia patients.Although prior studies have reported higher SARS\u2010CoV\u20102\u2010related mortality in patients with PD or dementia compared to patients without preexisting neurodegenerative diseases,Approval for LEOSS was obtained by the applicable local ethics committees of all participating centers and registered at the German Clinical Trials Register .(1) Research project: A. Conception: F.H., M.K.H., P.L., M.S., C.R., A.S., T.G., C.K., G.U.H. B. Organization: F.H., M.K.H., P.L., M.S., A.S., T.G., C.K., G.U.H., C.R., L.P. C. Execution: M.K.H., C.R., P.L., M.S., S.B., J.E., L.T., W.R., S.D., K.W., S.K., C.P., J.L., S.R., F.P., L.P., A.S., T.K., C.K., F.H., G.U.H. (2) Statistical analysis: A. Design: F.H., M.K.H., P.L., M.S., A.S., T.G., C.K., G.U.H. B. Execution: F.H., M.K.H. C. Review and critique: F.H., M.K.H., P.L., M.S., S.K., A.S., T.G., C.K., G.U.H. (3) Manuscript preparation: A. Writing of the first draft: F.H., M.K.H., P.L., M.S., C.R., A.S., T.G., C.K., G.U.H. B. Review and critique: M.K.H., C.R., P.L., M.S., S.B., J.E., L.T., W.R., S.D., K.W., S.K., C.P., J.L., S.R., F.P., L.P., A.S., T.K., C.K., F.H., G.U.H.Meret K. Huber, Claudia Raichle, Matthis Synofzik, Stefan Borgmann, Johanna Erber, Lukas Tometten, Wolfgang Rimili, Sebastian Dolff, Kai Wille, Samuel Knauss, Christiane Piepe, Julia Lanznaster, Siegbert Rieg, Fabian Prasser, Annika Spottke, and Thomas Klockgether report no disclosure. Paul Lingor is supported by the NUM research network of the BMBF (B\u2010FAST) and the Bavarian Staatsministerium f\u00fcr Wissenschaft und Kunst, and Lisa Pilgram is funded by the Willy Robert Pitzer Foundation. Christine Klein is supported by the B\u2010FAST Program (BMBF). Franziska Hopfner receives grants from the German Research Council (DFG), EASI\u2010Genomics Consortium (Horizon 2020), the Erwin\u2010R\u00f6ver\u2010Foundation, and the Else Kr\u00f6ner\u2010Fresenius Foundation. G\u00fcnter U. H\u00f6glinger is supported by the German Federal Ministry of Education and Research (BMBF: 01KU1403A EpiPD), Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy\u2014ID 390857198), DFG grants , the NOMIS foundation (FTLD project), the EU/EFPIA/Innovative Medicines Initiative, Joint Undertaking (IMPRIND grant number 116060) and by the Volkswagen Stiftung/Lower Saxony Ministry for Science/Petermax\u2010M\u00fcller Foundation (Nieders\u00e4chsisches Vorab \u2010 Etiology and Therapy of Synucleinopathies and Tauopathies). All authors are government employees.APPENDIX S1. Supporting InformationClick here for additional data file."} +{"text": "Scientific Reports 10.1038/s41598-021-81415-0, published online 12 February 2021Correction to: The original version of this Article contained an error in the spelling of the author Karim Yaqub Ibrahim which was incorrectly given as K. I. Ibrahim.As a result, the Author Contributions section now reads:\u201cN.S.F. assembled the data and drafted the manuscript. F.R., M.C.C.B. and S.C.G.A. assisted in MIC and serotype determination; F.M.T., P.R.B. and K.Y.I. assisted with the draft of manuscript; and E.A. designed, supervised, and assessed the study and drafted the manuscript. All authors have read, contributed, and approved the final manuscript.\u201dThe original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-020-70244-2, published online 21 August 2020Correction to: Daniel Butler was omitted from the author list in the original version of this Article.The Author contributions section now reads:\u201cJ.M.W. designed, conducted, and contributed to the writing of the manuscript, prepared Fig.\u00a01. S.G. evaluated and did statistical analysis on the skin and fat samples, prepared Figs. 2\u20139. J.O.A. evaluated and contributed to writing the manuscript. D.B prepared and sequenced DNA libraries for the skin microbiota data, and wrote the applicable parts of the methods section. C.M. analyzed and wrote up the skin microbiota data, prepared Fig.\u00a010. All authors have read the manuscript and approved its contents. D.D. analyzed and wrote up the skin microbiota data. S.Z. ran and analyzed the skin metabolite data. J.S. assisted in design, analysis and wrote up the skin metabolite data. J.K. assisted in analysis write up of skin and fat data. J.L.B. assisted in analysis, interpretation and writing of the manuscript. P.R.H. designed, analyzed, interpreted the data, and was the primary author of the manuscript.\u201dThis has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Cardiovascular diseases (CVDs), the leading cause of death worldwide, generally refer to a range of pathological conditions with the involvement of the heart and the blood vessels. A sizable fraction of the susceptibility loci is known, but the underlying mechanisms have been established only for a small proportion. Therefore, there is an increasing need to explore the functional relevance of trait-associated variants and, moreover, to search for novel risk genetic variation. We have reported the bioinformatic approach allowing effective identif ication of functional non-coding variants by integrated analysis of genome-wide data. Here, the analysis of 1361 previously identif ied regulatory SNPs (rSNPs) was performed to provide new insights into cardiovascular risk. We found 773,471 coding co-segregating markers for input rSNPs using the 1000 Genomes Project. The intersection of GWAS-derived SNPs with a relevance to cardiovascular traits with these markers was analyzed within a window of 10 Kbp. The effects on the transcription factor (TF) binding sites were explored by DeFine models. Functional pathway enrichment and protein\u2013protein interaction (PPI) network analyses were performed on the targets and the extended genes by STRING and DAVID. Eighteen rSNPs were functionally linked to cardiovascular risk. A signif icant impact on binding sites of thirteen TFs including those involved in blood cells formation, hematopoiesis, macrophage function, inf lammation, and vasoconstriction was found in K562 cells. 21 rSNP gene targets and 5 partners predicted by PPI were enriched for spliceosome and endocytosis KEGG pathways, endosome sorting complex and mRNA splicing REACTOME pathways. Related Gene Ontology terms included mRNA splicing and processing, endosome transport and protein catabolic processes. Together, the f indings provide further insight into the biological basis of CVDs and highlight the importance of the precise regulation of splicing and alternative splicing While the running data indicate that the prevalence of cardiovasculardisease may vary among regions of the world, theyremain one of the leading causes of death and health loss anda large proportion of their forms are shown to have a familialaggregation and high heritability . Theprevious efforts led to the identification of candidate risk genesincluding the genes of renal homeostasis for Mendelian formsof abnormal blood pressure levels and several transcriptionfactors for congenital septal. However, the broad groupof cardiovascular traits such as myocardial infarction/ischemiaor coronary artery disease (CAD) show complex inheritancepatterns, which suggest the collective and non-linear effectsfrom multiple genetic and non-genetic factors. With therecent technological advances, the whole-exome sequencing and genome-wide association studies, GWASs ) havebeen shown to be a powerful tool for discovering the geneticvariation associated with cardiovascular risk. The outcomesfrom multiple GWASs and their meta-analysis completedduring the past decade have been deposited in the catalogs,such as the catalog of published GWASs from The NationalHuman Genome Research Institute ,the Coronary ARtery DIsease Genome-wide Replication AndMeta-analysis, CARDIoGRAM plus TheCoronary Artery Disease (C4D) Consortium and UK Biobank.The genes related to regulating blood pressure, the tone andelasticity of the vascular wall, the inflammation process, theproliferation of vascular smooth muscle cells and the levels oflow density lipoprotein cholesterol (LDC-C) are \u2018traditionally\u2019involved in cardiovascular risk. Moreover, the GWA studiesresulted in numerous loci for cardiometabolic risk factors suchas plasma biomarkers of lipid metabolism, thrombosis, inflammationand metabolic status playing a role in risk analysis. Inthe case of long QT syndrome, in particular, fifteen candidategenes have been reported to date, including several genes forion channels . Notably,three candidates accountfor approximately 75 % of cases . Andthere are more than 150 suggestive loci estimated for CADalthough only 46 from them have reached the genome-widesignificance threshold . Interestingly,a considerable overlap has been shown between the risk genesfor monogenic forms of CVDs and those generating an associationsignal in GWAS .Together, these findings have developed a relatively comprehensiblepicture of the biology underlying the cardiovasculardisease, but despite the advances, we are not able to analyzethe functionality for the majority of the reported associatedgenetic loci. Among the reasons, there may be important limitationof GWAS for identifying risk genomic regions instead ofrisk genes and the non-coding localization of the majority ofthe susceptibility SNPs . Current theoriesassume that so-called regulatory non-coding SNPs (rSNPs)seem to make the greatest contribution to the developmentof various multifactorial diseases including oncological andCAD as these are directly involved in the control of the geneexpression levels.One of the lessons learned is the growing need for thecomprehensive post-GWAS analysis in order to translate thereported statistical association to uncover the causal variantsamongst those in linkage disequilibrium . Moreover, only some of GWASimplicatedloci arealso associated with \u2018classic\u2019 genes of risk, therefore showingthe potential involvement of \u2018non-traditional\u2019 biologicalpathways in the disease .Since the advances in next-generation sequencing technologieshave provided an expanding amount of large-scale-omics datasets, the research strategies have started to focuson the integration of various genome-wide information layers using functional genomics assays.One way to find putative functional variants is to detect regionswith allele-specific binding of transcription factors orhistone modifications, suggesting their different regulatorydownstream role. ChIP-seq data will provide the snapshots ofprotein-DNA interactions allowing the analysis of sites withsignificant difference in signal between the alleles or allelicdifferences. The employment of transcriptome (RNA-seq) datawill provide the snapshots of gene expression levels dependingon the allele. The epigenome (iTEA) analysis in combination with the regulatory sequence annotations,i. e. DNase-seq and ChIP-seq datasets , is beginning to be used to screen for the causal variantschanging gene expression, including within GWAS-derivedloci. However, the researchers have not come close to solvingthe issue of identifying the rSNPs at the genome-wide scale.The limitations are imposed by the incomplete experimental data collected to date and some critical methodologicalproblems. Notably, one of the major challenges has becomethe development of effective in silico (bioinformatic) approachesbut these are relatively few in number to date andonly the individual studies have been reported to elucidate theunderlying mechanisms of CVDs .To address the challenges, we have recently reported aneffective bioinformatic approach that facilitates the systematicidentification of functional non-coding variants from availablegenome-wide data . Our pipelineutilized multiple positional and functional criteria to revealnon-coding regulatory variants in the human genome and imputedcurated GWAS association signals to select the potentiallycolorectal cancer-causal rSNPs within a 1 Kb windowof genomic sequence centered at the GWAS-SNP. Initially, theregulatory properties of found rSNPs were shown on a numberof human cell lines of different origins . However, expression of tissue-specific transcriptionfactors is suppressed in cell lines. For this reason, here we haveadopted the list of 1361 regulatory SNPs from the said study.The data from 1000 Genomes Project were incorporated in the analysis toimprove matching rSNPs with the phenotypic outcome thatwould be the risk of CVDs. Further, we tried to narrow thefocus toward rSNPs that potentially result in a difference inpredicted binding status of various transcription factors andperformed the functional annotation of the targeted genes.Input data on non-coding regulatory variants in humangenome. Regulatory SNPs from our earlier study were used for input including the data on identifiedtargeted genes. All of these were associated with the allelespecificbinding of various TFs and allele-specific expressionfrom raw data.Genetics data. Genetic variants and allele information wereretrieved from dbSNP150 andfour 1000 Genomes Project super populations . The GRCh37 annotation was used to map genetic variantsto gene loci.Assessment of the SNP clustering with a distance measure.To map significant GWAS associations to novel functionalvariants here we implemented the data of 1000 GenomesProject. First, we extracted the data on 2500 individualhaplotype-resolved human genomes from various super populations. We found 1361 variantsfrom the 1476 input rSNPs reported earlier within this genomic data. Next, we extracted the dataon all SNPs within the transcribed genomic regions. The listsof rSNPs defined from 1000 genomes (\u2018population\u2019 set of1361 variant) and coding SNPs defined from 1000 genomeswere consolidated. Each individual from 2500 genomesamples was genotyped separately by each SNP from the consolidatedlist. The genotype data were turned to binary, where\u201c0\u201d represented the most frequent allele and \u201c1\u201d \u2013 the minorallele within the individual genotype. The resulting genotypedata were set to the 2D matrix containing 2500 individualgenomes and genotypes for all SNPs from the consolidated list. The initial matrix was then transformed to the distancematrix using XOR logic gate. Figure 1 shows an example ofSNP distance measurement by XOR.All the relative distances were normalized on the numberof times the minor allele was found there in the genomic dataof 2500 genomes. Based on the analysis of the resulting distances,we quantified the likelihood of the repeated recognitionof rSNPs and the coding SNP within one genotype in humanpopulations. Here we found that in total 773 471 coding SNPs( p <0.01) may be merely co-segregating markers for ourinput rSNPs.1Implementing GWAS data to interpret the input rSNPsfunctionality. Next, we examined GWAS index SNPs availableup to date (May 2019). We used the \u2018cardio\u2019 signaturefor querying the GWAS Catalog . Next, weevaluated whether the input rSNPs or any of the correspondingcoding markers lying within a 10 Kbp window of GWAS SNPs could be related to heart and vasculardisease association signals (Suppl. Table 1). https://disk.icgbio.ru/s/zBiq4fm632zRywe Supplementary Tables 1\u20134 are available in the online version of the paper:A functional protein association network. STRING v 11 was selected as the PPI database witha subset of 21 genes targeted by 18 rSNPs that were found tobe associated with cardiovascular risk, as input .Functional annotation by DAVID. DAVID Database forAnnotation, Visualization and Integrated Discovery was used to further interpret the sametargeted genes with the default values set for all parameters.The outputs of DAVID functional annotation and clusteringtools are given in the Suppl. Table 3.In silico analysis of potentially affected TF binding sites.The sequence-based DeFine deep learning models were employedto predict the effects on transcription factor binding inK562 cells (the data are accessible online via the DeFine tool)and to rank 18 rSNPs identified for cardiovascular risk. TheDeFine functional scores predict the transcriptional factor-DNA binding intensities and are appointed in the view of thedifferences between the reference sequence and the alteredsequence, as reviewed in . The outputsincluding the maximum TF functional scores, the most likelycandidate TFs and top 10 contact genes for each rSNP positionare given in the Suppl. Table 4.R code. The R package, version 3.1.0, was used for dataanalysis.The custom-made Perl scripts employed are availableupon request.Investigating rSNP functional relevanceto cardiovascular risk via GWAS associationsWe analyzed 438 GWAS-SNPs with relevance for cardiovasculartraits and defined eighteen candidate rSNP variants ata 10 Kbp window size (see Suppl. Table 1) including withinthe associated loci for coronary heart and artery disease , HLD cholesterol, QT interval, red blood cells andplatelet cells traits. One interesting result was that ten GWASderivedSNPs including the ones for phenotypical associationswith systolic and diastolic blood pressure, pulse pressure,retinal arteriolar microcirculation and one for CAD enteredthe list of founded regulatory SNPs in the study. We consideredthe input rSNP targets , and anygene targeted to these ten GWAS-SNPs to be a candidate for mediating the association. Actually,only one cardio-related SNP out of eighteen was linkedto more than one target gene: rs3744061 .Functional annotation of the rSNP targeted genesWe further looked into the target genes to these eighteencardio-vascular risk rSNPs as candidates for mediating theeffects on CVDs. In our STRING enrichment analysis , 21 rSNP targeted genes had five predictedpartners and these were shown significantly enriched in KyotoEncyclopedia of Genes and Genomes (KEGG) spliceosomepathway, two REACTOME pathways and40 Gene Ontology terms including gene expression, RNAsplicing, regulation of mRNA splicing, regulation of alternativemRNA splicing via spliceosome, protein transport tovacuole involved in ubiquitin-dependent protein catabolic processvia the multivesicular body sorting pathway; ubiquitindependentprotein catabolic process . Figure 2 showsthe corresponding protein association network with evidencefor association between the targets. Such an enrichment indicatesthat the input proteins are at least partially biologicallyconnected as a group.The same enriched groups were found by DAVID functionalannotation tool , including mRNAsplicing and mRNA 3\u2032-splice site recognition, regulation oftranscription and endosomal transport GO terms (see Suppl.Table 3). However, these processes could all be linked to thepathological features of CVDs, but the most notable is thegroup of targets that are associated with splicing and alternativesplicing regulation (given in red nodes).DeFine rSNP prioritizationThe DeFine online tool revealed that eight rSNPs had positivefunctional scores meeting the pathogenic potential to enhanceTF binding, and five \u2013 to weaken TF binding (see Suppl.Table 4) in the supported K562 cell line. The binding sites of ten TFs were most strongly altered by 13 rSNPs according toDeFine models: TAL1, REST, NR1H2, SP2, RFX5, MXI1,PBX2, NFYB, ZNF274 and ZNF263. Nine out of ten of theseTFs (with the exception of ZNF274) were the proteins withantibodies to which the immunoprecipitation was made bythe original authors . This would be expected in principlewhen examining certain regulatory regions.In more detail, rs210962 (GWAS-derived) and rs7920217functional variants shared the potential to weaken the bindingof RE1 silencing transcription factor (REST) to the relatedgenomic loci .rs2270574 and rs8106212 within the GWAS locifor CAD and platelet trait, respectively, shared the associationwith SP2 transcription factor, but had the opposite effects onTF binding according to DeFine scores . And again,two rSNPs shared the effects on TF binding sites for T-cellacute leukemia protein 1 (TAL1) in this study: rs140492 withinthe locus for HDL cholesterol (DeFine score 0.0996 to enhancethe TF binding was counted) and rs10445033 \u2013 within GWASlocus for red blood cell levels with the DeFine score \u20130.0891to weaken the TF binding. Again, DeFine identified the sametargeted genes (i. e. SNF8 for rs2270574) with additional potentialtargets in each rSNP case .As has been mentioned in the Results, we have identifiedeighteen rSNPs with a functional relevance to CVDs thatmatched the GWAS loci for coronary heart and artery disease,HLD cholesterol, retinal arteriolar microcirculation, QT interval,red blood cells and platelet cells traits from this study(see Suppl. Table 1). The genome position of rSNP coincidedwith that for GWAS-derived SNP for ten identified variantsout of eighteen. It was an interesting find as this was a relativelylarge part compared to our previously reported resultsfor colorectal cancer and cognitivedisorders .As has been mentioned in the Results, we have identifiedeighteen rSNPs with a functional relevance to CVDs thatmatched the GWAS loci for coronary heart and artery disease,HLD cholesterol, retinal arteriolar microcirculation, QT interval,red blood cells and platelet cells traits from this study(see Suppl. Table 1). The genome position of rSNP coincidedwith that for GWAS-derived SNP for ten identified variantsout of eighteen. It was an interesting find as this was a relativelylarge part compared to our previously reported resultsfor colorectal cancer and cognitivedisorders .What we should like to mention is that a number of trulycritical processes depend on the blood cells functionality andbiological activities as has been widely demonstrated. Regardingerythrocytes, these include not only oxygen transport,but immune response , redox homeostasis and regulation of vascular function . Moreover, several ex vivostudies on diabetes mellitus identified that red blood cells doact to mediate the development of endothelial dysfunctionand cardiac injury . This means that any qualitative or quantita-tivedeviations from the physiological ranges may be closelylinked to the disease . The data suggest thatthe blood cell count and hematological parameters could beuseful markers to improve the cardiovascular risk prediction;however, they have limited sensitivity . Interestingly, it was shown that the level of expressionof some curated genes may independently aid in the predictionof heart failure prognosis when combined with neutrophilto-lymphocyte ratio . The risk for CVDs correlates well with platelet traits , theinitiation and progression of CAD in particular . However, some have argued that shared genetic pathwayslinking blood cells with complex pathologies, includingautoimmune diseases, schizophrenia, and CAD may be noncausal.Still, our current knowledge of splicing regulation and alternativesplicing in the heart is limited, but splicing analysis hasemerged as an important line of research for the cardiovascularrisk. The studies revealed that the regulation of splicing andalternative splicing events ) seem to play a causative role in heart developmentand cardiovascular disease. The promising therapeutic targets have already been proposed. There isevidence that a significant number of alternate transcripts areincreased in diseased hearts compared to controls, and canbe involved in disease. Thus, abnormal splicing of apoptoticgenes contributes to the pathogenesis of several CVDs includingdilated and diabetic cardiomyopathy, atherosclerosisand heart failure as reviewed in . Thedysregulation of cardiac splicing factors can also be sufficientto affect heart function and lead to disease. Thus, there isevidence that the decrease in RNA-binding motif protein 20(RBM20) levels may be involved in dilated cardiomyopathyby providing input to splicing of at least several known targetgenes . In the study, the target gene of thers4360494 functional variant within the GWAS-derived locusfor pulse pressure is the SF3A3 gene that encodes subunit 3of the splicing factor 3a protein heterotrimeric complex. Asis known, the splicing factor 3a plays an important role in U2snRNP biogenesis and thus, pre-mRNA splicing . With respect to other pathologicalstates, targeting the components of the spliceosome hasfull potential as a strategy for cancer treatment and prognosis. Thus, the data suggest that SF3A3 is involved inthe p53 activation, the induction of cell cycle arrest and celldeath in non-small cell lung cancer . The SRSF2 gene, encoding another splicing machinerycomponent, could be used as a reliable prognostic factor inpatients with hepatocellular carcinoma .The role of endosomal system in the heart functioning andcardiovascular disease is described as critical, too , as endosomes contribute to control of cholesterol(LDL) plasma levels , Ca2+ homeostasisand protein trafficking and play an importantpart in atherosclerosis risk . However,surprisingly little is known regarding the regulation of endosome-based protein trafficking in the heart. Thus, our resultscould serve as useful background for further research. Proteinquality and control and ubiquitin-proteasome system, UPS have also played anessential role in the initiation and progression of CVDs. Inshort, the findings suggest that UPS contributes to structuralremodeling of the myocardium, ischemia-reperfusion injuryand myocardial cell loss, important components of progressiveheart failure. There is evidence for the non-degradative role aswell, as the ubiquitination was shown to affect the important regulators of signaling pathways including those for the cellgrowth and apoptosis, DNA damage response, the innate immuneresponse, endocytosis, and protein activity ). Given that proteostasis is a dynamicmultiple-step process involving complex molecularmachinery, the deregulation at any stage could therefore beimplicated in a wide variety of outcomesWhen addressing directly the list of targets for our 18 rSNPsthat are likely relevant to cardiovascular function, a memberof the VAV gene family \u2013 VAV1 is the target of the rs8106212variant for platelet distribution. Overall, the VAV proteinsare known to interact with the receptors on cell surface toactivate various downstream biological pathways thus leadingto the alterations of transcription. VAV1 is important inhematopoiesis, playing a role in T-cell and B-cell developmentand activation . Anothercandidate, the PIEZO1 gene targeted by rs10445033 is widelyassociated with hereditary human diseases andtissue homeostasis . The homotetramerof the PIEZO1 protein functions as a pore-forming subunit ofa mechanically activated cation channel and contributes a lotto vascular biology and development includingmechanistic signaling in endothelium . Some studies suggest that the molecular eventsinvolved in the development of acute myocardial infarctionmay include MiR-103a microRNA expression in plasma andthe subsequent regulation of the expression of PIEZO1 protein. However, the up-regulation ofPiezo1 was demonstratedin rat model of heart failure .Since the rSNPs do induce the variation in the gene expression,the significant rSNPs\u2019 effects on the binding affinityof a genomic locus for transcription factors can be a cause. There is relative evidence for theGWAS loci for complex diseases to be associated with not onlyultimate changes in gene expression but with the activity of various TFs .Here, we used the online classifier of variant pathogenicity,DeFine , to explore the functional effectsof 18 rSNPs with the relevance to cardiovascular traits on theTF binding sites. DeFine classification approach employs thesequence-based deep learning models between the referencesequence and the altered sequence centered at the variant. Theauthors have shown that the given tool is capable to identifythe causal non-coding variants within the reported GWAS locifor complex human diseases.In this study, a significant functional impact on bindingsites of thirteen TFs, including five genomic positions withpotentially weakened and eight \u2013 with potentially enhancedTF binding, was found in K562 cells. Among ten identifiedTFs with maximum DeFine functional scores (see Suppl.Table 4), four TFs werefunctionally reliable to CVDs when considering well-knownroles. Thus, TAL1 is the erythroid differentiation factor thatcooperates with various TFs to regulate hematopoiesis andnormal differentiation of myeloid cells, and may also contributeto the process of malignant transformation . PBX genes encode homeodomain transcriptionfactors, that were shown to determine the allele-specific phenotypicpresentation of heart defects in mice and their loss resulted in the insufficient expression of both genes controllingthe blood vessel widening and narrowing and finally led topersistent vasoconstriction by multiple pathways . NFYB (nuclear transcription factor Y subunitbeta) is a subunit of a highly conserved trimeric TF thatbinds with high specificity to CCAAT motifs in the promoterregions in a variety of genes. Interestingly, the evidence forNf-y, SP family factors (that bind to GC-boxes) and PBX1 tocooperate was identified .It is important that the regulatory elements of genome, thedistribution of TF binding sites, and the effects of rSNPs onthe gene expression can be highly tissue or cell line specific. But since the tissue samples, in particularof the brain and heart, are very difficult to obtain from humans,it is not surprising that the approaches to genome-wide identifyingof the functional variants were trained and available incells and animal models first. It can be argued that genomewidestudying of the functional effects of non-coding variantson transcription very often relies on the modeling of the celltype-specific binding of transcription factors to regulatory elementsof genome. The interest in the field of reliable in silicomethods is increasing, but there are only a few that have beenmore or less broadly implemented according to PubMed analysis. Moreover, the evidence suggeststhat the performance of different functional prediction toolsvaries by disease phenotype andthus may give contradictory statements.Overall, to date, using GWAS associations seems the mostcommon way to explore the non-coding variants in the termsof functionality. Still, a survey from published studies showedthat this approach helps to interpret just a minor part of thousandsof identified rSNPs . Ourresults suggest that the reported analysis pipeline integratingthe datasets from 1000 Genomes Project may serve as a generalframework for future research and would eventually leadto investigation of novel functional variants within significantGWAS loci that confer human disease risk. Considering ourpreviously obtained data for colorectal cancer and a number of cognitive disorders , we have more evidence for the precise regulationof splicing mechanisms and alternative splicing to be amongthe key mechanisms underlying the effects of non-codinggenetic variation on the phenotype including various pathologicalconditions.Overall using GWAS associations seems the most commonlyused way to explore the non-coding variants in the terms offunctionality to date. Still, a survey from published studiesshowed that this approach helps to interpret just a minor part ofthousands of identified rSNPs . Ourresults suggest that the reported analysis pipeline integratingthe datasets from 1000 Genomes Project may serve as a generalframework for future research and would eventually leadto investigation of novel functional variants within significantGWAS loci that confer human disease risk. In consideration ofour previously obtained data for colorectal cancer and a number of cognitive disorders , we have got another evidence for the preciseregulation of splicing mechanisms and alternative splicing to be among the key mechanisms underlying the effects of noncodinggenetic variation on the phenotype including variouspathological conditions.The authors declare no conflict of interest.1000 Genomes Project Consortium, Auton A., Brooks L.D., DurbinR.M., Garrison E.P., Kang H.M., Korbel J.O., Marchini J.L.,McCarthy S., McVean G.A., Abecasis G.R. A global reference forhuman genetic variation. Nature. 2015;526:68-74. DOI 10.1038/nature15393.Albarr\u00e1n-Ju\u00e1rez J., Iring A., Wang S., Joseph S., Grimm M., Strilic B.,Wettschureck N., Althoff T.F., Offermanns S. Piezo1 and Gq/G11promoteendothelial inflammation depending on flow pattern andintegrin activation. J. Exp. Med. 2018;215(10):2655-2672. DOI10.1084/jem.20180483Alper S.L. Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction. 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Information from summary statistics canbe used for multiple purposes \u2013 from fundamental research in biology and genetics to the search for potentialbiomarkers and therapeutic targets. While the amount of GWAS summary statistics collected by the scientific community is rapidly increasing, the use of this data is limited by the lack of generally accepted standards. In particular,the researchers who would like to use GWAS summary statistics in their studies have to become aware that the dataare scattered across multiple websites, are presented in a variety of formats, and, often, were not quality controlled.Moreover, each available summary statistics analysis tools will ask for data to be presented in their own internalformat. To address these issues, we developed GWAS-MAP, a high-throughput platform for aggregating, storing,analyzing, visualizing and providing access to a database of big data that result from region- and genome-wideassociation studies. The database currently contains information on more than 70 billion associations betweengenetic variants and human diseases, quantitative traits, and \u201comics\u201d traits. The GWAS-MAP platform and databasecan be used for studying the etiology of human diseases, building predictive risk models and finding potential biomarkers and therapeutic interventions. In order to demonstrate a typical application of the platform as an approachfor extracting new biological knowledge and establishing mechanistic hypotheses, we analyzed varicose veins, adisease affecting on average every third adult in Russia. The results of analysis confirmed known epidemiologic associations for this disease and led us to propose a hypothesis that increased levels of MICB and CD209 proteins inhuman plasma may increase susceptibility to varicose veins. Genome-wide association studies (GWAS) are one of themain approaches for identifying associations between geneticvariants and traits . One of the mostimportant advantages of this approach is that it is agnosticto the molecular mechanisms or biochemical nature of thetraits or diseases under study, thus allowing fundamentallynew knowledge to be obtained. Based on the functions of thegenes mapped by a GWAS, researchers aim to discover newmolecular mechanisms underlying the development of traitsand pathologies under consideration.GWAS are performed on large samples of genotyped andphenotyped individuals to identify statistically significant associations between single-nucleotide polymorphisms(SNPs)and traits . SNPs are located relativelyhomogeneously and with sufficient density, consequently,functional variants occurring at high frequency in the population are detected with a high probability, either becausethe causative allele is being tested directly or because it isin linkage disequilibrium with genotyped markers. A specialcase of GWAS is a regional genetic study of associations ora region-wide association study (RWAS), where the analysisis applied to SNPs in a particular region instead of the wholegenome. RWAS is used, for example, to find cis-SNPs associated with the expression of a certain gene .The GWAS approach has become very popular over thepast decade. Since 2007 the number of GWAS has increasedexponentially and hundreds of original genome-wide studiesare published every year. The earliest GWAS addressed theassociations between a single trait and several hundreds ofthousands SNPs, using samples of several hundreds or thousands individuals .Currently, both the number of analyzed traits and the genomic coverage of GWAS have increased by many orders ofmagnitude . This has become possibledue to the advent of new sequencing and genotyping technologies and the improvement of existing ones, as well as othermethods for studying biological objects, leading to an increasein the resolution of sequencing, genotyping and phenotyping.Modern GWAS normally assess associations with millions of SNPs and in some cases the sample size exceeds one millionpeople . The number of phenotypesstudied can go to hundreds , thousands and even tens of thousands, e. g. for \u201c-omics\u201d traits. Thesame trait is analyzed in multiple studies, often with progressively increasing sample sizes, as well as in new populations,offering increased power and generalizabilityThe direct results of GWAS/RWAS consist of files withsummary statistics. These files can include up to ten of millions rows, where each row contains information about theassociation between a given SNP and the investigated trait.Taking into account the number of GWAS studies and the sizeof the files with results, GWAS results qualify as Big Data. Importantly,not only does this body of data grow, but so do the rates ofdata acquisition. GWAS results can be used to address a large number ofproblems ranging from fundamental biology and genetics tothe search for biomarkers and targets for therapeutic interventions. Currently, a range of methods has been developed thatimplement the solution of these problems based on summarystatistics data.In particular, methods have been developed to define sets ofSNPs that are most likely to contain the true functional variantat loci suggested by GWAS . For example, this problem isaddressed by the PAINOR softwareand the conditional and joint analysis as implemented in theGCTA tool .Also, identification of causal genes influencing a trait of interest is possible through the use of summary statistics. By regulating the expression of those genes or bymanipulating their products through the use of, for example,pharmacological interventions, the trait of interest can beaddressed in a targeted manner. Several instruments implement these methods, for example, the SMR (Summary-levelMendelian Randomization) tool . The samemethods can often be used to study pleiotropic effects . The results of studies ofpleiotropy can be used for drug repositioning, for predicting possible side effects of gene editing, and for prediction ofpossible side effects of pharmacological manipulation of theproducts of these genesOver the past decade, the number of studies using Mendelian randomization methods has increased substantially,providing important new information about disease etiology. Mendelian randomization methodscombined with the use of summary statistics and multipleinstrumental variables can help to reconstruct the theoretical hierarchy of causeand effect relationships between traits and, in practice, havethe potential to be used for the identification of traits that canbe targeted by therapeutic interventions.Methods for studying genetic correlations can be particularly useful inaddressing fundamental questions related to the genetic architecture of complex traits. One of these methods is implementedin a popular LDsr (Linkage Disequilibrium score regression)python package .Finally, summary statistics from GWAS can be used inmethods to develop models for the prediction of quantitativetraits and disease risks for a given individual or group .The simplest of these models use effects of the most significantindependent SNPs . If a GWAS involvesa large number of cases and controls, powerful predictorscan be developed for some traits even with simple models,breast cancer being a well-known example . Methods allowing the researcher to manage information about millions of SNPs and whole-genome LD structurewhile developing a prediction model have recently becomepopular . Such models were usedfor predicting the risk of ischemic heart disease , type 2 diabetes , and obesity.Although the amount of GWAS results obtained by thescientific community is constantly growing, as are the numberof methods for their analysis, they have currently found onlylimited use. The problems researchers face when workingwith these data are multiple. First, summary statistics filesfrom GWAS are large (more than tens of terabytes), and sotheir storage and processing require dedicated infrastructure.Secondly, data are produced by different laboratories usingdifferent protocols, and consequently, quality control and aharmonization procedure for storing such data in a commonformat are required. Thirdly, the existing tools for analyses ofsummary statistics data from GWAS are implemented usingdifferent languages, hosted at different repositories and websites and require custom input data formats. Finally, large-scaleadoption of these methods and data require user interfaces forresearchers without specialized bioinformatics skills.The existing solutions are incomplete or partial. On theone hand, resources such as GWAS Central or GWAS Catalog (https://www.ebi.ac.uk/gwas/) can do as much , but originally they were intendedfor handling \u201csmall data\u201d , and so their architecture does not scalewell enough to handle big data and the requirements of newmethods for processing GWAS results. On the other hand, most software applications , GCTA , LDsr ) are intended for analyzing data rather than foraggregating, storing or providing access to them. Finally,the portals MR-Base (http://www.mrbase.org/) and LD Hub(http://ldsc.broadinstitute.org/) can aggregate and store GWASresults and allow the user to conduct specify types of analysis;however, these portals do not offer anything for other methodsof analysis, and software solutions for data aggregation andstorage are not available.To help address these issues, we developed the GWASMAP platform for aggregating, storing, analyzing, visualizing and providing access to big data obtained from GWAS.The name GWAS-MAP means both a map between phenotypes and genotypes, but is also an abbreviation of MultipleAnalyses Platform. Using GWAS-MAP we collected GWASMAP|homo database of GWAS and RWAS results for humantraits. Currently, the database contains more than 70 billionassociations between SNPs and human traits. GWAS-MAPprovides an opportunity to carry out research that will contribute to the search for new biomarkers that has a bearing onthe development of high-efficacy drugs and also reveal sideeffects in existing drugs. We have performed a genetic analysisof varicose veins to demonstrate how the platform works.GWAS-MAP software architectureThe GWAS-MAP platform consists of two data processingmodules and a database (DB) module .Data integration starts with the conversion of summary statistics files collected from various sources into a universal dataformat. After conversion, we perform quality control (QC)and if the summary statistics pass, they are uploaded to thedatabases.The DB module is the part responsible for setting up thedatabases and tables structure required for the GWAS-MAPplatform. The DB module consists of two components, eachcontrolled by a separate open source database managementsystem (DBMS). One of the components is used to store theGWAS summary statistics; for this component the ClickHouseDBMS version 19.16.2. revision 54427 (https://clickhouse.tech/) is used. Arecord in this system contains the parametersof association between certain SNP and a trait. The other component contains (1) meta-data that gives particular informationabout the summary statistics collected from articles, studyweb-sites or other sources, and (2) the results of analyses; forthis component the PostgreSQL DBMS version 10.6 (https://www.postgresql.org/) is used.With the analysis module a user can run various analyses onthe GWAS/RWAS summary statistics using the integrated analytical tools written in Python, which are accessible throughcommand-line utilities.Integration and quality control of GWAS/RWAS resultsThe platform offers users the option to upload GWAS summary statistics files of their own original research. Becausethese data were generated using different protocols, the resulting summary statistics files may appear in different formats. To address this, GWAS-MAP provides an integration moduleconverting summary statistics files to a common format andperforming QC on the data.To ensure data consistency within the DB, informationabout a SNP\u2019s identifier, position in the genome, and allelesand allele frequencies are compared with reference data. Thereference is a list of SNPs with their main characteristics:the identifier (rsID), chromosome, position, alleles and allelefrequencies. At present, the reference is based on the 503 genomes of European-ancestry individuals from the \u201c1000 Genomes\u201d project phase 3 version 5 .In general, summary statistics contain all fields requiredfor unification in a universal format. If some fields are absent,then the missing information is added from the reference or calculated from the informationin the input file. For example, it is possible to recover thestandard error of the effect size based on the effect size andp-value.Before uploading GWAS/RWAS data to the DB, it is absolutely necessary to have them passed through QC. QC isindispensable not only for meta-analyses of GWAS/RWASresults, but also for verifying separate studies, because seemingly insignificant data errors may lead to heavily biasedresults later on.We have developed a QC module which spots outlyingSNPs and assesses the overall quality of the input data. More specifically, QC includes (1) a comparison of the frequencies ofalleles from the input data with those from the reference set,a comparison of the p-values provided in the study and thosecalculated from the Z-statistics (if present), (2) an analysisof the distribution of estimates of the allele effect sizes,(3) calculation of the trait variance and (4) genomic controlfactor (\u03bbGC). SNPs whose characteristics depart by more thana threshold value from those expected are labeled as outliersand can be filtered out by the user. If the summary statisticsfrom GWAS have more than 5 % outliers, or the effect size distribution is not symmetric, this data will be not recommended for upload, although the final decision is up to a user.We should notice that all current data in DB have passed theabove described criteria.Analysis methods using GWAS/RWAS summary statisticsimplemented in GWAS-MAPGWAS-MAP incorporates several widely used methods forthe analysis of GWAS/RWAS summary statistics with specialemphasis on the identification of genes, molecules, traits andfunctional SNPs that appear as potential targets of therapeuticinterventions. In particular, data processing can be carried outusing the following methods.Linkage disequilibrium score regression is a method to assess the heritability of a trait and to calculate genetic correlations between two traits . Thismethod was implemented in Python 2 by Bulik-Sullivanand co-authors (2015). We have re-written it in Python 3because it is the main programming language used forGWAS-MAP and because Python 2 has been deprecatedsince January 1, 2020. This also allowed us to optimize itfor working with our DBs.Mendelian randomization methods \u2013 a set of tests that allow to infer causal relationships between two traits . Hemani and colleagues provided an opensource R package, which includes such methods. To this,we added a module for reading summary statistics from theGWAS-MAP DB in the required formatSummary-level Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) are the teststo ascertain whether two different traits are associated withthe same locus (SMR) and whether this association canbe explained by the null hypothesis of pleiotropy or byan alternative hypothesis that each trait is associated withdifferent SNPs in linkage disequilibrium (LD) (HEIDI). We implemented the SMR-HEIDI testsourselves for the GWAS-MAP platform. The rationale behind this was mainly that the SMR tool developed by Zhu and colleagues (2016) specializes in testing pleiotropy between the level of gene expression (RWAS) and a complextrait (GWAS), but not between two sets of GWAS resultssummary statistics.We also implemented the \u03b8 metric defined by Momozawaet al., which assesses the similarity between associationprofiles using only summary statistics and is an alternative to the HEIDI test. This method is preferable when theLD information of the population used in a GWAS is lacking or unreliable . The \u03b8 metricas implemented in GWAS-MAP is based on the equationsprovided in the article .Finally, the GWAS-MAP platform implements severalstandard methods for meta-analysis which can be applied toa pool of GWAS results of the same trait in order to obtainenhance power . GWAS-MAP has amodule for checking the quality of the GWAS results tobe used in meta-analyses and a module for meta-analysis.We have implemented two methods for meta-analysis:inverse-variance weighting and Z-score .GWAS-MAP|homo database contentTo allow the researcher to filter GWAS/RWAS according tocertain criteria, the platform offers key information includingthe publication data, reference set used for imputations, thename/type of the DNA microarray or whole-genome sequencingused in each study. Currently, the DB contains more than70 billion associations between SNPs and traits, collected from7281 GWAS and more than a million RWAS (see the Table).To give a reader an idea of the context, such popular databasesas \u201cGWAS central\u201d provides informationon 71 million of associations, while Phenoscanner \u2013 65 billion.The GWAS and RWAS in the DBs are assigned to the following domains: complex traits (including diseases), metabolites (mQTL), proteins (pQTL), glycans and gene expressiondata. Additionally, the GWAS and RWAS results coming fromthe same study are pooled in a collection. The presence ofGWAS traits from different domains enables the researcherto conduct a comprehensive study of the trait of interest, toidentify ways of how the trait of interest is influenced by theexpression levels of genes, proteins and metabolites, and tolook for associations with other diseases or quantitative traits.Varicose veins (VV) is a widely prevalent disease affecting onaverage every third adult in Russia .The genetic basis of this pathology has long been poorlystudied. Shadrina and co-authors have performed the firstlarge-scale study of its genetic architecture using a range ofmodern methods in bioinformatics as implemented in GWASMAP The study used UK Biobank (http://www.ukbiobank.ac.uk/)data on 408,455 individuals of European descent. GWASsummary statistics of VV were retrieved from the open accessdatabases Gene ATLAS and theNeale Lab website . Shadrina and co-authorsidentified 12 genetic loci associated with VV which accountfor 13.4 % of the SNP-based heritability. A gene or a groupof genes most probably involved in VV pathogenesis wasprioritized for each locus. The SMR-HEIDI implementationin GWAS-MAP was used as one of the prioritization methods.With SMR-HEIDI, we searched for the genes for which theexpression levels are associated with SNPs affecting VV risk. Theanalysis relied on data from the eQTL (expression quantitativetrait loci) domain, namely data of 44 tissues in the GTEx_v7 and blood_eQTL collections. Colocalization was demonstratedfor the following loci: rs3101725 (associated with the expression level of the long non-coding RNA LINC01184 in9 tissues), rs2241173 (associated with the expression levelof the non-coding RNA AC005152.3 in the lower extremityskin) and rs2861819 (associated with expression levels of thePPP3R1 gene in blood). Because the functions of LINC01184and AC005152.3 are not yet known, we may only speculateabout the role of these RNAs in VV. As far as PPP3R1 isconcerned, its association with VV appears to be more sound.Its product is involved in the inflammatory response in thevascular wall, stimulating the production of the chemokineMCP-1 , which is consistent with themodern view of the pathogenesis of chronic venous disease. Additionally,Smetanina and co-workers demonstrated enhanced PPP3R1expression in VV specimens compared to unaffected veins.In addition to gene prioritization, SMR-HEIDI was used tosearch for traits associated with VV-related functional variants.The analysis involved 2219 traits, including various diseases,levels of metabolites and proteins in blood, and revealed32 traits associated with 6 loci. The traits can conventionallybe divided into three main groups: one associated with bodyweight and the total metabolic rate; a second with blood testresults, and a last one with all others.The GWAS-MAP platform was also used for the analysisof genetic correlations between VV and 861 traits, the summary statistics of which were obtained by analyzing more than10 thousand individuals. The analysis showed the presenceof common genetic variance between VV cases and 62 traits.Some of these traits were already known from previous epidemiological studies: overweight, standing and heavy physicalwork, deep venous thrombosis, gonarthrosis, and pain in thelegs when walking. Other traits that, at the genetic level, correlate with VV, such as intellect, memory, educational attainment, or whole-body pain, have not previously been reportedas associated with VVFinally, Shadrina and co-workers used Mendelian randomization for the analysis of causal relationships between various traits and VV. Analysis results showed that the followingtraits directly influence the risk for VV: height (irrespective ofweight), body weight; waist and hip circumferences, and theblood levels of two proteins, MICB and CD209 . Curiously, the risk for VV increased with anincrease of both body fat and fat-free mass. Data on height asa risk factor for VV are consistent with the Edinburgh VeinStudy results . MICB and CD209 participatein the innate and the adaptive immune response. Becausepresented work is the first to propose that these proteins haveroles in VV pathogenesis, we think it reasonable to repeatthe analysis with an independent dataset. If the Mendelianrandomization results are confirmed, these proteins can be regarded as promising candidates for further in vivo and in vitrostudies aimed at finding therapeutic targets.The GWAS-MAP platform offers a broad range of opportunities for comprehensive analysis of GWAS results. We expect that GWAS-MAP will be helpful both for bioinformaticsstudies and as a reference source for medical researchers. Forexample, given a trait of interest, it is possible to compute whatother traits it is genetically associated with, i. e., is controlledby overlapping sets of genetic variants. More generally, notonly correlations between traits can be calculated, but alsoall pairwise correlations between the traits in the DB. Theresults can be used to cluster the traits and/or to build a network connecting traits that have a shared genetic basis . Furthermore,the Mendelian randomization methods implemented in theplatform will help to elucidate which of these associationsare causal. Thus, it is possible to build a directed graph forinteractions between traits. By considering a particular vertex,for example, \u201cdisease\u201d, it is possible to infer what metabolites,glycans and/or proteins can be used as its biomarkers.If a researcher\u2019s interest lies with a locus or loci associated with a certain GWAS of interest, it is also interesting toconsider colocalization. With SMR-HEIDI and the \u03b8 metric,it is possible to understand with the expression of what genesthe GWAS loci are associated. Additionally, by analysis ofRWAS results for the genes of interest and GWAS resultsin the domains for metabolites, proteins and/or glycans, itis possible to infer what biological processes are associatedwith changes in the expression of these genes. A large-scaleanalysis of colocalization will help to build networks of associations between traits in the DB and genes. These networkswill be helpful in developing medications. Not only will theyshow what genes can be targeted, but also what implicationsand side effects of manipulations with the gene may entail.However, it should be kept in mind that these analyses aredone in silico and therefore, and experimental validation isabsolutely required.A large number of methods have already been implementedin the platform \u2013 however, there are certainly more to come.Our short-term plans include the addition of new analysismethods: Depict , CoJo ,and SbayesR . We are planning todevelop a web-interface to allow external users to access ourDBs and perform analyses. Such a web-interface will guidethe user through the search for information about the association between a SNP and traits and will be convenient fore. g. medical researchers. We continue adding new data to thedatabase and we are working on making GWAS-MAP usefulfor human populations other than Europeans.We have developed the GWAS-MAP platform for aggregating,storing, analyzing, visualizing and providing access to summary statistics from GWAS and RWAS. Using the platform wecollected GWAS-MAP|homo DB which contains over 70 billion associations between SNPs and traits. The GWAS-MAPuser interface offers a universal workspace for operating onpublic and private data, and allows for rapid implementation ofnew analysis methods in the platform. The user communicateswith the platform through command-line utilities, allowinghim to upload data to the platform and run analyses.The analysis of the genetic basis of varicose veins demonstrates the power of the platform for generating new biologicalhypotheses such as, for example, ours postulating a causal relationship between the levels of the proteins MICB andCD209 in blood and the risk for this disease.GWAS-MAP is a powerful platform for the analysis ofsummary statistics from GWAS and RWAS, it is activelyused in research work and can be useful to a broad range ofscientists. The platform evolves continuously through constantacquisition of more functionalities, and the DBs are updatedwith the actual data from GWAS and RWAS.The authors declare no conflict of interest.Beck T., Shorter T., Brookes A.J. GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies. Nucleic Acids Res.2020;8(48):D933-D940. 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Saccharomyces boulardii and Lactobacillus reuteri significantly reduced the risk of diarrhea lasting \u22652 days when compared with placebo or no treatment, with moderate evidence. Among all probiotics, Saccharomyces boulardii may be the most effective in reducing both duration of diarrhea (compared with placebo) and risk of diarrhea lasting \u22652 days (compared with placebo or no treatment), with moderate evidence. To be conclusive, Saccharomyces boulardii may be the most effective probiotic for treating acute diarrhea in children, followed by several other single-strain and multi-strain probiotics.Acute diarrhea is a major cause of morbidity and mortality in children under five. Probiotics are beneficial for treating acute diarrhea in children, but unclear which specific probiotic is the most effective. We performed a Bayesian network meta-analysis to examine the comparative effectiveness of probiotics. By searching EMBASE, PubMed, and the Cochrane Library up to 31 March 2021, randomized clinical trials (RCTs) on probiotics for treating acute diarrhea in children were included. Primary outcomes included the duration of diarrhea and diarrhea lasting \u22652 days, and secondary outcomes included the mean stool frequency on day 2 and duration of hospitalization, fever, and vomiting. We assessed the certainty of the evidence of outcomes according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline. Eighty-four studies with twenty-one different interventions in 13,443 children were included. For the primary outcomes, moderate evidence indicated that, Diarrhea is common among infants, usually acute, which is mainly caused by infection . In 2017Intestinal microbiota, which is closely associated with human health, has been a research hotspot. The derangement of intestinal microflora is the hallmark of diarrhea . ProbiotOral rehydration solution (ORS) is the mainstay treatment modality for diarrhea. However, it cannot halt the progression of diarrhea, nor address microflora imbalance, pathogen clearance, and environmental enteric dysfunction ,12, all The NMA was performed following the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement ,20. We hBy searching the Cochrane Library, PubMed, and EMBASE, randomized controlled trials of probiotics for treating acute diarrhea in children were included. We limited our search to English. The search date for these databases ended on 31 March 2021. The search terms included: diarrhea, probiotic, children, and randomized controlled trial .Studies were included in this NMA if they met the following inclusion criteria: (1) RCT; (2) children (age \u2264 18 years) with acute diarrhea (the frequency of diarrhea was more than three times during a 24-h period and the duration of diarrhea was less than 14 days); (3) children were randomly assigned to receive probiotics, placebo, or no treatment; (4) the study must report at least one of the outcomes . We excluded the following articles: non\u2013English papers, non-randomized trials, studies with malnourished children, studies without children, studies without probiotics, studies without acute diarrhea, case reports, reviews, meta-analysis studies, conference abstracts, animal studies, in vitro experiments, and letters.Two investigators independently read the full texts of the included literature and extracted the data. Any disagreements were resolved by discussion. The extracted data included first author, publication, year, country, sample size, probiotic species, and outcomes of interest .Two investigators independently used Review Manager 5.3 (Cochrane Collaboration) to evaluate the quality of the included studies according to the Cochrane risk of bias assessment tool . In addip-value < 0.05.The NMA was performed with the \u201crjags\u201d and \u201cgemtc\u201d packages in R software (version 4.0.1). Network plots were done by STATA (version 14.0). The NMA was conducted with a Bayesian hierarchical model framework . It was Heterogeneity assessment was performed using the I\u00b2 index and \u03c7\u00b2 test. The probability ranking of intervention was achieved by calculating the surface under the cumulative probability ranking curve (SUCRA) . The conA total of 3927 records were retrieved by searching EMBASE, PubMed, and the Cochrane Library. Five studies were found from references. Following the removal of duplicates, 528 potentially eligible articles were identified. Ultimately, eighty-four studies that met the inclusion criteria were included in the NMA. The flow of literature screening is detailed in Eighty-four studies with twenty-one different interventions involving a total of 13,443 children were included ,109,110.Saccharomyces (S.) boulardii, Lactobacillus rhamnosus GG (LGG), Lactobacillus (L.) reuteri, Bacillus clausii, L. acidophilus, Bifidobacterium (B.) lactis, L. sporogenes, L. plantarum, Escherichia coli nissle 1917 (ECN 1917), L. paracasei, and Enterococcus (E.) faecium. Multiple-strain probiotics included L. species (spp.), L. spp. + B. spp., L. spp. + B. spp.+ S. spp., L. spp. + S. spp., B. spp. + S. spp., Bacillus spp. + E. spp. + Clostridium (C.) spp., L. spp. + B. spp. + E. spp., L. spp. + B. spp. + Pediococcus spp., and L. spp. + S. spp. + C. spp. + Bacillus spp. In addition, the control arms included both placebo and no treatment.Probiotic interventions could be divided into single-strain and multi-strain probiotics. The single-strain probiotics included There was no statistical difference or inconsistency for diarrhea lasting \u22652 days, mean stool frequency on day 2, and duration of hospitalization, vomiting, and fever . In addiB. lactis had the highest probability of reducing the duration of diarrhea , L. reuteri , B. lactis , L. spp. + B. spp. + S. spp. , and Bacillus spp. + E. spp. + C. spp. significantly reduced the duration of diarrhea. In addition, very low or low evidence showed that ECN 1917 , L. spp. + B. spp. , and L. spp. + Bacillus spp. + S. spp. + C. spp. could decrease the duration of diarrhea when compared to placebo , LGG , L. reuteri , B. lactis , L. spp. + B. spp. , L. spp. + B. spp. + S. spp. , and L. spp. + B. spp. + E. spp. . B. lactreatment .S. boulardii and L. reuteri with moderate evidence. Low evidence indicated that L. spp. + B. spp. and L. spp. + B. spp. + S. spp. contributed to the significant effect and LGG significantly decreased the duration of hospitalization with low evidence , LGG , L. reuteri , L. spp. + B. spp. + S. spp. , and Bacillus spp. + E. spp. + C. spp. could decrease the mean stool frequency on day 2. L. spp. + B. spp. showed the significant effect could reduce the duration of vomiting when compared to the controls ; 40 studies (48%) were judged at \u201clow risk\u201d for allocation concealment; 39 (46%) were classified as \u201clow risk\u201d for blinding of children\u2019s parents and personnel; 31 (37%) were classified as \u201clow risk\u201d for blinding of outcome assessment; 62 (74%) represented \u201clow risk\u201d for incomplete outcome data .L. reuteri and S. boulardii could reduce the duration of diarrhea, the risk of diarrhea lasting \u22652 days, and the mean stool frequency on day 2. Evidence with a low or very low certainty suggested that B. lactis, LGG, and ECN 1917 could shorten the duration of diarrhea. For multi-strain probiotics, L. spp. + B. spp. + S. spp. could decrease the duration of diarrhea and the mean stool frequency on day 2 with moderate evidence. Low evidence indicated that L. spp. + B. spp., Bacillus spp. + E. spp. + C. spp., L. spp. + B. spp. + E. spp., and L. spp. + Bacillus spp. + S. spp. + C. spp. could decrease the duration of diarrhea. Only Bacillus spp. + E. spp. + C. spp. could reduce the duration of vomiting with moderate evidence. Remarkably, for the primary outcomes, S. boulardii may be the most effective in reducing the duration of diarrhea (compared with placebo) and the risk of diarrhea lasting \u22652 days (compared with placebo or no treatment) with moderate evidence.Diarrhea not only seriously endangers the long-term physical development health of children but also poses a substantial socioeconomic burden ,111. In Our study demonstrated that probiotics could facilitate antidiarrheal effects on acute diarrhea in children, which was consistent with a previous report . PreviouS. boulardii vs LGG and S. boulardii vs B. lactis; S. boulardii (moderate evidence), L. reuteri (moderate evidence), B. lactis (low evidence), and ECN 1917 (very low evidence) could shorten the duration of diarrhea. Interestingly, LGG significantly reduced the duration of diarrhea compared with no treatment, but such the effect was not observed compared with placebo. It was consistent with the previous study by Szajewska et al. [For the duration of diarrhea, we identified significant heterogeneity and inconsistency in the two comparisons , the risk of diarrhea lasting \u22652 days (moderate evidence), and the mean stool frequency on day 2 (moderate evidence). Therefore, we recommend S. boulardii as the best probiotic for the treatment of acute diarrhea in children. However, S. boulardii was present in some human stools but was not found in most children. It has been reported in cases of fungal sepsis [S. boulardii\u2019s antidiarrheal effect. Low evidence indicated that B. lactis ranked the first in reducing the duration of diarrhea when compared with placebo or no treatment. Several studies suggested that B. lactis could improve gut barrier function, enhance immunity against pathogens, and regulate intestinal flora, thereby facilitating overall health recovery [S. boulardii may be more effective than B. lactis in reducing the duration of diarrhea. Therefore, we recommend, but inferior to S. boulardii, that B. lactis treats acute diarrhea in children. More randomized controlled trials are required to verify the effectiveness of B. lactis.In addition to reducing the duration of diarrhea, l sepsis . More strecovery ,115. HowL. spp. + B. spp. + S. spp. possibly decreased the duration of diarrhea (moderate evidence), the risk of diarrhea lasting \u22652 days (low evidence), and the mean stool frequency on day 2 (moderate evidence). It suggested that the combination of Lactobacillus spp., Bifidobacterium spp., and Saccharomyces spp. produced a significant effect. Together with the above results of the NMA, we recommend a mixture of LGG, L. reuteri, B. lactis, and S. boulardii to treat acute diarrhea in children. Remarkably, the success of probiotic treatments may be reduced in well-nourished, rotavirus-vaccinated children, resulting in a signal-to-noise problem. Two large RCTs involving almost 1000 children reflected it [In pediatrics, several studies have found that multi-strain probiotics were effective, even better than single-strain probiotics ,117,118.ected it ,40.Limitations to the NMA need to be acknowledged. First, several studies did not provide the mean and standard deviation. We performed the data estimation of them based on median, quartile, range, and sample size, so that the authenticity of some data was not high. Second, malnutrition and HIV-infected children were not included in the NMA. However, diarrhea contributed to a significant share of morbidity and mortality in these children in the sub\u2013Sahara African region ,2. ThirdIn the NMA, we illustrated the clinical effect of single-strain and multi-strain probiotics and determined the comparative effectiveness of various probiotics. To our knowledge, it is the first network meta-analysis that systematically evaluates the effectiveness of probiotics for treating acute diarrhea in children. Our results showed that probiotics could reduce the duration of diarrhea in children by 1\u20132 days. Probiotics may be cost-effective for treating acute diarrhea in children because probiotics are cheap. The results of this study may provide a valuable reference for decision-making in a clinical setting.Saccharomyces boulardii, LGG, Lactobacillus reuteri, Bifidobacterium lactis, and ECN 1917) and multi-strain probiotics effectively treated acute diarrhea in children with various certainty evidence. Saccharomyces boulardii may be the most effective probiotic for treating acute diarrhea in children. Besides, Bifidobacterium lactis was a promising probiotic. More studies are needed to verify the results.In the Bayesian network meta-analysis of 84 studies involving 13,443 children, we found that certain single-strain (including"} +{"text": "Nature Communications 10.1038/s41467-018-08025-9, published online 16 January 2019.Correction to: The original version of this Article omitted the following from the Acknowledgements:R. R. F., V. G. S. and J. F. have also been funded by the Spanish Ministerio de Econom\u00eda y Competitividad and Ministerio de Ciencia e Innovaci\u00f3n .This has now been corrected in both the PDF and HTML versions of the Article."} +{"text": "Apiospora is known as a cosmopolitan genus, found across various substrates. In this study, four Apiospora taxa were obtained from the decaying stems of bamboo and maize in northern Thailand. Apiospora collections were compared with known species based on the morphological characteristics and the DNA sequence data of internal transcribed spacer (ITS), the partial large subunit nuclear rDNA (LSU), the translation elongation factor 1-alpha gene (TEF1-\u03b1) and beta-tubulins (TUB2). Apiospora chiangraiense sp. nov. and two new host records (Ap. intestini and Ap. rasikravindra) are introduced here based on the morphological characteristics and multi-locus analyses. Additionally, thirteen species previously identified as Arthrinium are introduced as new combinations in Apiospora, viz., Ap. acutiapica, Ap. bambusicola, Ap. biserialis, Ap. cordylines, Ap. cyclobalanopsidis, Ap. euphorbiae, Ap. gelatinosa, Ap. locuta-pollinis, Ap. minutispora, Ap. pseudorasikravindrae, Ap. septate, Ap. setariae and Ap. sorghi.The genus Apiospora was introduced by Saccardo with Ap. montagnei as the type species [Apiospora was characterized by basauxic conidiogenesis, with globose to subglobose conidia, which are usually lenticular in the side view, obovoid and pale brown to brown [Apiospora are similar in morphology, thus it is difficult to distinguish them without molecular phylogenetic data. The size, color and shape of conidia and the morphology of conidiophores should be used together to better identify them. For example, conidiophores of some species reduce to conidiogenous cells , while some species have semi-micronematous to macronematous conidiophores . species . The gen species ,3,4. Theto brown ,5,6. SpeApiospora species have a worldwide distribution and can be found from various hosts [Apiospora species are associated with plants as endophytes, pathogens or saprobes, especially on bamboo [Apiospora species can cause leaf necrosis and twig dieback in the olive tree (Olea europaea), leaf edge spot of the peach (Prunus persica), blight disease of bamboo (Schizostachyum), leaf spot of rosemary , kernel blight of barley (Hordeumvulgare) and brown culm streak of Phyllostachys praecox [us hosts ,7,8,9. Mn bamboo ,3,10,11.n bamboo ,3,10,11. praecox ,15,16,17 praecox ,21,22,23Arthrinium and Apiospora have long been debated after Ellis [Apiospora was synonymized under Arthrinium by Crous et al. [Apiospora is the sexual morph of Arthrinium and phylogenetic analyses showed that the two genera formed a monophyletic clade. Meanwhile, the phylogenic analyses results from Pintos et al. [Arthrinium forms a monophyletic clade that separates from all other sequences of Apiospora and suggested that Arthrinium s. str. could actually be phylogenetically different from Apiospora, but this is in need of clarification using the phylogeny of additional species before making a conclusive taxonomic decision on the issue. Recently, Pintos and Alvarado [Apiospora and Arthrinium present independent lineages, thus they separate well into two genera.The morphological relationships between er Ellis , as the s et al. as they s et al. showed AAlvarado showed tApiospora are more or less rounded in the face view and lenticular in the side view and conidiophores sometimes develop forming acervuli. Whereas the conidia of Arthrinium are variously shaped and the conidiophores of some species have thick blackish septa [Apiospora species are mostly reported on Poaceae, while Arthrinium species commonly occur on Cyperaceae and Juncaceae. Moreover, Apiospora has a worldwide distribution, and species in the genus can be found from tropical and subtropical areas to the Mediterranean, temperate and cold regions, while Arthrinium species are rarely found from tropical and subtropical habitats. Hence, Pintos and Alvarado [Arthrinium species were transferred to Apiospora based on the phylogenetic analyses. Presently, 117 records of Apiospora are listed in the Index Fungorum [Morphologically, the conidia of sh septa . EcologiAlvarado considerFungorum .Apiospora and describe the three taxa that were isolated from maize and bamboo in Chiang Rai province, Thailand. Based on the morphological characteristics and phylogenetic analyses of a combined dataset of the internal transcribed spacer (ITS), the partial large subunit nuclear rDNA (LSU), the translation elongation factor 1-alpha gene (TEF1-\u03b1) and beta-tubulins (TUB2), a new species, Ap. chiangraiense, as well as two new host records, Ap. rasikravindrae and Ap. intestini, are introduced. In addition, thirteen species of Arthrinium were synonymized under Apiospora.The aims of this study are to determine the phylogenetic placement of the genus Fresh specimens of bamboo and maize culms with fungal fruiting bodies were collected from Chiang Rai, Thailand from September\u2013October 2020. Specimens were brought to the laboratory in plastic Ziploc bags for observation. Senanayake et al. were folThe herbarium specimens have been deposited at the herbarium of Mae Fah Luang University (MFLU) and Kunming Institute of Botany (HKAS), while the living cultures have been deposited at Mae Fah Luang University Culture Collection (MFLUCC). The Faces of Fungi and the Index Fungorum numbers are registered as outlined in Jayasiri et al. , and theThe genomic DNA was extracted from living pure cultures using the Biospin Fungus Genomic DNA extraction Kit following the manufacturer\u2019s protocol. The internal transcribed spacer (ITS) with the primer pair of ITS4/ITS5 , the parApiospora taxa to the taxa obtained in this study. The sequences of Apiospora were also obtained from recently published data [http://mafft.cbrc.jp/alignment/server, accessed on 12 August 2021) [The sequences generated in this study were subjected to a basic local alignment search tool (BLAST) search in the GenBank to identify closely related hed data ,37,38,39st 2021) , and manst 2021) .Sporocadus trimorphus (CBS 114203) as the outgroup taxon. The models were selected as GTRGAMMA for maximum likelihood, while the best-fit models were selected as GTR + I + G for ITS, LSU and HKY + I + G for TUB2, and TEF1-\u03b1 for the Bayesian posterior probability analysis. The maximum likelihood (ML) analysis was performed using RAxML-HPC v.8 [https://www.phylo.org, accessed on 12 August 2021) [The construction of the combined phylogenetic trees was completed using maximum likelihood (ML) and Bayesian inference posterior probabilities (BYPP), with us CBS 1103 as the-HPC v.8 on the Xst 2021) with a rst 2021) . Markov st 2021) and modiSporocadus trimorphus (CBS 114203) as the outgroup taxon. Multi-locus sequences were concatenated, which comprised 2820 nucleotide characters, including gaps . The phylogenic tree from the RAxML analysis had similar topology to the Bayesian analysis. The RAxML analysis of the combined dataset yielded the best scoring tree . The strain MFLUCC 21-0052 presented as a distinct lineage and sister to Ap. intestine (CBS 135835) with significant statistical support (ML/BI = 100/1.00). The strain MFLUCC 21-0053 clustered with Ap. intestine (CBS 135835), but in a distinct clade with high support (ML/BI = 100/1.00).The phylogenetic trees generated by maximum likelihood and Bayesian show the taxonomic placements of our total strains belong to Apiospora chiangraiense X.G. Tian and Tibpromma S., sp. nov. , monoblastic or polyblastic, aggregated in clusters on hyphae, hyaline to light brown, smooth and cylindrical to subcylindrical. Conidia are aseptate, pale brown to dark brown, in the surface view 6.5\u20138 \u00d7 6\u20138 \u03bcm2 , in the lateral view 6\u20137.5 \u00d7 4\u20135.5 \u03bcm2 , with a central scar, globose in the surface view, a lenticular inside view, with straight germ slit spore length.Culture characteristics: Conidia germinating on PDA within 24 h at room temperature (25 \u00b0C). On the PDA, the colonies\u2019 surfaces are white, lightly yellow, wooly, flat, spreading, filiform, with abundant aerial mycelia and reverse off-white to yellow.Material examined: THAILAND, Chiang Rai Province, Muang District, on dead culms of bamboo, 23 October 2020, X.G. Tian, bb-4-5, ; ex-type culture, MFLUCC 21-0053.Apiosporachiangraiense formed a distinct clade sister to Ap. intestini with strong bootstrap support values (ML/BI = 100/1.00). Morphologically, Ap. chiangraiense is distinct from Ap. intestine by conidiogenous cells, conidiophores and conidia. The conidiophores of Ap. intestini are usually hyaline, macronematous, mononematous and transversely septate, while Ap. chiangraiense has reduced conidiophores and conidiogenous cells grouped together to form sporodochia. Additionally, Ap. chiangraiense has larger conidia compared to Ap. intestini 5.5 (\u20136) \u03bcm diam, side view (2\u2013) 4 (\u20136) \u03bcm diam). Based on pairwise nucleotide comparisons, Ap. chiangraiense is different from Ap. intestini (CBS 135835) in 27/583 bp (4.63/) of the ITS, 9/814 (1.1%) of the LSU and 61/696 bp (8.76%) of TUB2, but we were unable to compare TEF-\u03b1 pairwise nucleotides as the amplification of TEF-\u03b1 was not successful for this species. However, both the phylogenetic analyses and morphological characteristics supported our species as a distinct new species.Notes: In the phylogenetic analyses, Apiospora intestini Pintos and P. Alvarado, Fungal Systematics and Evolution 7: 206 (2021) (6 (2021) .Index Fungorum number: IF 837744.Saprobic on dead culms of bamboo. Sexual morph: undetermined. Asexual morph: Colonies are on natural substrate surface, gregarious, powdery, dark brown to black, dull with conidia readily liberated when disturbed. Conidiophores are 1.5\u20132 \u00b5m wide , intercalary, cylindrical, hyaline. Conidia are 6.5\u20135 \u00d7 6\u201310 \u00b5m2 , borne as bunches on conidiophores, lateral, pale brown to brown, smooth-walled, globose to subglobose or irregularly round, aseptate, with a central scar and without germ slit.Culture characteristics: Conidia germinating on PDA within 24 h at room temperature. The colonies\u2019 surfaces are white, cottony, flat, spreading, filiform, mycelia not tightly attached to the surface and the reverse lightly pigmented.Material examined: THAILAND, Chiang Rai Province, Muang District, on dead culms of bamboo, 23 October 2020, X. G. Tian bb-4-2 (MFLU 21-0045), living culture, MFLUCC 21-0052.Apiospora intestini was introduced by Crous et al. [Ap. intestini with relatively high support (ML/BI = 100/1.00). Morphologically, the conidia of the new isolate (MFLUCC 21-0052) are similar to the holotype Ap. intestini (CBS 135835) in having similar size of conidiophores that are borne as bunches, intercalary and terminal, brown, smooth, aseptate and globose to subglobose. Based on nucleotide comparisons, Ap. intestini (MFLUCC 21-0052) is slightly different from Ap. intestini in 12/580 bp (2.07%) of the ITS, 2/814 (0.24%) of the LSU, 2/684 bp (0.29%) of TUB2 and 2/610 bp (0.32%) of TEF1-\u03b1. Based on both phylogeny and morphology, the new isolate (MFLUCC 21-0052) is identified as Ap. intestini. This is the first report of Ap. intestini (MFLUCC 21-0052) isolated from dead culms of bamboo in Thailand, which was originally isolated from a grasshopper\u2019s gut in India.Notes: s et al. based onApiospora rasikravindrae Pintos and P. Alvarado, Fungal Systematics and Evolution 7: 207 (2021) (7 (2021) .Index Fungorum number: IF 837716; Faces of Fungi number: FoF 01994.Saprobic on dead culms of bamboo. Colonies appear as spotty patches on natural substrate surface. Conidiomata are immersed, pycnidial, scattered, globose to slightly conical, ostiolate, black, coriaceous. Conidiophores are 9\u201326 \u00d7 1\u20132.5 \u03bcm2 , arising mostly from swollen basal cells, micro to semi-macronematous, mononematous, unbranched, straight or flexuous, smooth and thin-walled, hyaline. Conidiogenous cells are basauxic, discrete, hyaline, smooth-walled. Conidia in surface view are 9\u201311 \u00d7 9\u201310.5 \u03bcm2 , in lateral view 10\u201311 \u00d7 6.5\u20138 \u03bcm2 , lenticular, globose to ovoid, occasionally elongated to ellipsoidal, brown to dark brown, smooth-walled, with a longitudinal, thin-walled, with a pale equatorial slit.Saprobic on dead culms of bamboo, 23 October 2020, X. G. Tian, bb-4-1 (MFLU 21-0044), living culture, MFLUCC 21-0051; ibid decaying maize culms, 11 November 2020, X. G. Tian, corn-1-1 (HKAS 115764), living culture, MFLUCC 21-0054Material examined: THAILAND, Chiang Rai Province, Muang District, isolated as Apiospora rasikravindrae (LC 8179) , while the new isolate (MFLUCC 21-0051) also showed high similarities with Apiospora rasikravindrae (LC 8179) . Our phylogenetic analyses showed that the two new isolates clustered with the ex-type strain of Ap. rasikravindrae (NFCCI 2144) and Ap. rasikravindrae (LC 8179). Morphologically, our new isolate is closely related to the holotype of Ap. rasikravindrae in having lenticular, globose to ovoid, occasionally elongated to ellipsoidal, brown to dark brown, smooth-walled, germ-slit conidia and micro-semi-macronematous, mononematous, unbranched, straight or flexuous, smooth and thin-walled and hyaline conidiophores. Hence, the two new isolates are identified as Ap. rasikravindrae.Notes: The National Center for Biotechnology Information (NCBI) BLAST results of ITS, LSU, TUB2 and TEF1-\u03b1 sequences of our new isolate (MFLUCC 21-0054) showed high similarities with Apiospora rasikravindrae was originally isolated from soil in Norway [Apiospora rasikravindrae occurred on Capsicum, Kappaphycus alvarezii, Pinus, Platanus acerifolia, rice, Sargassum thunbergia and Triticum aestivum from Brazil, China, India, Japan, Netherlands, Svalbard and Thailand [Ap. rasikravindrae and it was collected on the stems of bamboo. In this study, the isolate MFLUCC 21-0051 was newly collected from bamboo, while the isolate MFLUCC 21-0054 was newly recorded from maize.n Norway . ApiospoThailand ,48. Dai Thailand describeApiospora acutiapica (Senan. and Cheew) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558499.Basionym: Arthrinium acutiapicum Senan. and Cheew, Frontiers in Microbiology 11. 2020.Arthrinium acutiapicum was introduced by Senanayake et al. [Bambusa bambos in China. Senanayake et al. [Ar. pseudorasikravindrae, which is a sister to Ar. acutiapicum, by the reduction of conidiophores to conidiogenous cells, cylindrical to ampulliform, pale brown conidiogenous cells with pointed, hyaline apex and brown to dark brown and smooth-walled conidia with a dark equatorial slit [Notes: e et al. and was e et al. mentioneial slit .Arthrinium acutiapicum clustered with Apiospora pseudorasikravindrae (=Ar. pseudorasikravindrae) with high support (ML/BI = 95/-). Thus, we propose the transfer of Ar. acutiapicum under the new combination Ap. acutiapica, based on the morphological and phylogenetic analyses.In our phylogenetic analysis based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora bambusicola X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558493; Faces of Fungi number: FoF 09162.Arthrinium bambusicola X. Tang, K.D. Hyde and J.C. Kang, Biodiversity Data Journal 8 (e58755): 11 2020.Basioym: Arthrinium bambusicola was introduced by Tang et al. [Schizostachyum brachycladum in Thailand. Tang et al. [Ar. bambusicola were retrieved as a sister taxon of Ar. gutiae with high support (ML/BI = 83/0.99), but differs from Ar. gutiae in having larger conidia and irregularly rounded, guttulate to roughened conidia. Pintos and Alvarado [Ar. gutiae to Apiospora based on the phylogenetic analyses and morphological characters.Notes: g et al. and was g et al. mentioneAlvarado transferArthrinium bambusicola is a sister to the newly introduced species Ap. chiangraiense with high support (ML/BI = 80/0.99). Thus, we propose the transfer of Ar. bambusicola under the new combination Ap. bambusicola, based on the morphological and phylogenetic analyses.In our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora biserialis (Y. Feng and Z.Y. Liu) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558502; Faces of Fungi number: FoF 09569.Basioym: Arthrinium biseriale Y. Feng, J.K. Liu, C.G. Lin, Y.Y. Chen, M.M. Xiang and Z.Y. Liu, Frontiers in Microbiology 12. 2021.Arthrinium biseriale was introduced by Feng et al. [Ar. biseriale is closely related to Ar. gelatinosum, but they are phylogenetically distinct and can be recognized as two different species. Morphologically, Ar. biseriale has smaller stromata and the spores of Ar. biseriale are more curved than those of Ar. gelatinosum [Notes: g et al. from deag et al. showed tatinosum .Arthrinium biseriale clustered with Apiospora gelatinosa with high support (ML/BI = 90/0.99). Thus, we propose the transfer of Ar. biseriale under the new combination Ap. biserialis, based on the morphological and phylogenetic analyses.In our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora cordylines X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558494.Basionym: Arthrinium cordylines T.Z. Chen, Yong Wang bis and K.D. Hyde, Mycotaxon 136(1): 189 2021.Arthrinium cordylines was introduced by Chen et al. [Cordyline fruticosa in China. Chen et al. [Ar. cordylinae formed a well-supported branch with type strains of Ar. aureum (CBS 244.83) and Ar. hydei (CBS 114990). Meanwhile, a base difference comparison also confirmed Ar. cordylinae is a distinct species.Notes: n et al. from then et al. mentioneArthrinium cordylines is a sister to Ap. hydei with high support (ML/BI = 96/0.99). Thus, we propose the transfer of Ar. cordylines under the new combination Ap. cordylines.In our phylogenetic analyses, Apiospora cyclobalanopsidis (Y. Feng and Z.Y. Liu) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558503; Faces of Fungi number: FoF 09572.Basioym: Arthrinium cyclobalanopsidis Y. Feng, J.K. Liu, C.G. Lin, Y.Y. Chen, M.M. Xiang and Z.Y. Liu, Frontiers in Microbiology 12. 2021.Arthrinium cyclobalanopsidis was introduced by Feng et al. [Cyclobalanopsidis glauca Oerst in China. Feng et al. [Ar. cyclobalanopsidis clustered with Ar. camelliae-sinensis, but can be distinguished from Ar. camelliae-sinensis by conidiogenous cells. Pintos and Alvarado [Ar. camelliae-sinensis to Apiospora camelliae-sinensis, based on the phylogenetic analyses and morphological characteristics.Notes: g et al. from a lg et al. showed tAlvarado transferArthrinium cyclobalanopsidis clustered with Ap. camelliae-sinensis with high support (ML/BI = 78/1.00). Thus, we propose the transfer of Ar. cyclobalanopsidis under the new combination Ap. cyclobalanopsidis, based on the morphological and phylogenetic analyses.In our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora euphorbiae (M.B. Ellis) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558495.Arthrinium euphorbiae M.B. Ellis, Mycol. Pap. 103: 6 1965.Basioym: Arthrinium euphorbiae was introduced by Ellis et al. [Euphorbia in Zambia. Tang et al. [Ar. euphorbiae is phylogenetically closely related to Ar. malaysianum, Ar. vietnamensis, and Ar. chromolaenae [Notes: s et al. from theg et al. showed tmolaenae ,18.Ar. euphorbiae is a sister to Ap. malaysiana with strong bootstrap support values (ML/PP = 94/0.99). Thus, we propose the transfer of Ar. euphorbiae under the new combination Ap. euphorbiae.In our phylogenetic analyses, Apiospora gelatinosa (Y. Feng and Z.Y. Liu) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558504; Faces of Fungi number: FoF 09570.Basioym: Arthrinium gelatinosum Y. Feng, J.K. Liu, C.G. Lin, Y.Y. Chen, M.M. Xiang and Z.Y. Liu, Frontiers in Microbiology 12. 2021.Arthrinium gelatinosum was introduced by Feng et al. [Ar. gelatinosum is a sister to Ar. biseriale with a well-supported lineage (ML/MP/BI = 93/98/1.00) [Notes: g et al. from deag et al. mentione98/1.00) .Arthrinium gelatinosum clustered with Apiospora biserialis with high support (ML/BI = 90/0.99). Thus, we propose the transfer of Ar. gelatinosum under the new combination Ap. gelatinosa.In our phylogenetic analyses, Apiospora locuta-pollinis (F. Liu and L. Cai) Pintos and P. Alvarado), X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: 834523; Faces of Fungi number: FoF05221.Synonyms: Arthrinium pseudomarii T.Z. Chen, Yong Wang bis and K.D. Hyde, Mycotaxon 136(1): 189. 2021.Basionym: Arthrinium locutum-pollinis F. Liu and L. Cai (as \u2018locuta- pollinis\u2019), Mycosphere 9: 1094. 2018.Arthrinium pseudomarii was introduced by Chen et al. [Aristolochia debilis in China. Chen et al. [Ar. pseudomarii differs from Ar. hispanicum, Ar. marii and Ar. mediterranei by larger, subglobose to ellipsoid conidia and showed a close relationship with three species with high bootstrap support values (ML/MP = 95/93) [Notes: n et al. from then et al. mentione= 95/93) .Ar. pseudomarii (GUCC 10228) is a sister to Ap. locuta-pollinis (=Ar. locuta-pollinis) with high support of 95% ML. Based on the nucleotide comparisons, Ar. pseudomarii is slightly different from Ap. locuta-pollinis in 10/582 bp (1.72%) of ITS, but no base pair differences were observed in TUB2 and TEF1-\u03b1. Morphologically, the conidia of Ar. pseudomarii are similar to the holotype Ap. locuta-pollinis (LC 11683) in having similar size, brown with a hyaline equatorial rim, smooth, subglobose to ellipsoid condia and hyaline to pale brown, smooth, ampulliform to doliiform conidiogenous cells aggregated into clusters on the hyphae. Thus, we identified that they are the same species, and we synonymize Ar. pseudomarii under the Ap. locuta-pollinis, based on the morphological and phylogenetic analyses.In our phylogenetic analyses, Apiospora minutispora X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558497.Basionym: Arthrinium minutisporum K. Das, S.Y. Lee and H.Y. Jung, Mycobiology 48(6): 453 2020.Arthrinium minutisporum was introduced by Das et al. [Ar. minutisporum is quite similar to Ar. phragmites, Ar. aureum and Ar. Hydei. However, the conidia of Ar. minutisporum are smaller than those of Ar. phragmites, Ar. aureum and Ar. Hydei, and Ar. minutisporum produce smaller conidiogenous cells than Ar. phragmites [Ar. phragmites, Ar. aureum and Ar. hydei to Apiospora phragmites, Ap. aureum and Ap. hydei, based on the phylogenetic analyses and morphological characteristics. Whereas Ar. minutisporum was maintained in Arthrinium.Notes: s et al. from mouragmites . Pintos ragmites transferArthrinium minutisporum forms a distinct subclade and is close to Apiospora aurea, Ap. balearica and Ap. descalsii with strong bootstrap support values (ML/PP = 99/1.00) within Apiospora. Thus, we propose the transfer of Ar. minutisporum under the new combination Ap. minutispora.In our phylogenetic analyses, Apiospora pseudorasikravindrae (Senan. and Cheew) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF 558505.Arthrinium pseudorasikravindrae Senan. and Cheew, Frontiers in Microbiology 11. 2020.Basionym: Notes: Arthrinium pseudorasikravindrae was introduced by Senanayake et al. from deaAr. pseudorasikravindrae is a sister to the new combinations Ap. acutiapica(=Ar. acutiapicum) with high support (ML/BI = 77/0.99). Thus, we propose the transfer of Ar. pseudorasikravindrae under the new combination Ap. pseudorasikravindrae.Our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data show Apiospora septata (Y. Feng and Jian K. Liu) X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558506; Faces of Fungi number: FoF 09571.Basioym: Arthrinium septatum Y. Feng, J.K. Liu, C.G. Lin, Y.Y. Chen, M.M. Xiang and Z.Y. Liu, Frontiers in Microbiology 12. 2021.Arthrinium septatum was introduced by Feng et al. [Arthrinium septatum forms a well-supported clade and appears to be distinct from other Arthrinium species. Arthriniumseptatum resembles Ar. biseriale in having a biseriate, broad fusiform to cylindrical ascospores and cylindrical, clavate asci. However, Ar. septatum differs from Ar. biseriale by having smaller stromata [Notes: g et al. from deag et al. showed tstromata .Arthrinium septatum groups in a well-supported clade with Ap. pseudospegazzinii and Ap. gelatinosa. Thus, we propose the transfer of Ar. septatum under the new combination Ap. septata, based on the morphological and phylogenetic analyses.In our phylogenetic analyses, Apiosporasetariae X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF835609.Arthrinium setariae JIANG, N.; TIAN, C.M. Phytotaxa 483, 149-159. 2021.Basioym: Arthrinium setariae was introduced by Jing et al. [Setaria viridis in China. Jing et al. [Ar. jiangxiense. Pintos and Alvarado [Ar. jiangxiense to Apiospora and synonymized Ap. jiangxiens based on the phylogenetic analyses and morphological characteristics.Notes: g et al. from Setg et al. mentioneAlvarado transferArthrinium setariae clustered with Apiospora jiangxiense with high support (ML/BI = 87/1.00). Thus, we propose the transfer of Ar. setariae under the new combination Ap. setariae, based on the morphological and phylogenetic analyses.In our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora sorghi X.G. Tian and Tibpromma S., comb. nov.Index Fungorum number: IF558498; Faces of Fungi number: FoF 05762.Basioym: Arthrinium sorghi J.D.P. Bezerra, C.M Gon\u00e7alves and C.M. Souza-Motta, Fungal Diversity: 10.1007, 73 2020.Arthrinium sorghi was introduced as an endophyte by Bezerra et al. [Sorghum bicolor in Brazil. Bezerra et al. [Ar. sorghi is treated as a unique lineage within Arthrinium based on ITS phylogenetic analysis. Morphologically, Ar. sorghi resembles Ar. pseudosinense, Ar. ovatum and Ar. phaeospermum, but differs from them by the culture characteristics, conidiophores and conidia size [Ar. pseudosinense, Ar. ovatum and Ar. phaeospermum to Apiospora pseudosinensis, Ap. ovata and Ap. phaeospermum based on the phylogenetic analyses and morphological characteristics.Notes: a et al. from thea et al. mentionedia size . Pintos dia size transferArthrinium sorghi clustered with Apiospora bambusucila with high support (ML/BI = 78/0.99). Thus, we propose the transfer of Ar. sorghi under the new combination Ap. sorghi, based on the morphological and phylogenetic analyses.In our phylogenetic analyses based on combined LSU, ITS, TEF1-\u03b1 and TUB2 sequence data, Apiospora chiangraiense and two new host records, viz., Ap. intestini and Ap. rasikravindrae, are introduced based on the morphological and phylogenetic analyses. In addition, thirteen new combinations are proposed based on the phylogenetic analyses.In this study, the new taxon Apiospora was previously synonymized under Arthrinium, but Pintos et al. [Apiospora based on a phylogenetic analysis. Currently, 117 species of Apiospora are listed in the Index Fungorum [Apiospora by phylogenetic analyses [Apiospora and Arthrinium are quite similar, so it is difficult to distinguish Apiospora and Arthrinium based only on morphology.s et al. re-evaluFungorum . Among tanalyses ; howeverArthrinium species, viz., Arthrinium trachycarpum and Ar. urticae, formed a distinct clade out of Arthrinium, and this result is consistent with previous studies [Arthrinium; thus, more collections are required to clarify the placement of these two species [Apiospora sorghi, Ap. bambusucila, Ap. chiangraiense and Ap. intesini are not clustered together in Apiospora major clades (Apiospora species, but a few base pair differences were found. Moreover, their morphologies fit well within the species concept of Apiospora. Thus, further phylogenetic analyses are necessary to confirm whether Apiospora is a species complex or not.In the phylogenetic analyses, two studies . However species ,50. In ar clades . We also"} +{"text": "Front. Neuroinform. 11:14. 10.3389/fninf.2017.00014.\u201d It should instead be written as \u201cBlenkmann, A. O., Phillips, H. N., Princich, J. P., Rowe, J. B., Bekinschtein, T. A., Muravchik, C. H., et al. (2017). iElectrodes: a comprehensive open-source toolbox for depth and subdural grid electrode localization. Front. Neuroinform. 11:14. 10.3389/fninf.2017.00014,\u201d with \u201cBlenkmann et al., In the original article, the reference for Antonio Valdes-Sosa et al., 2017 was incorrectly written as \u201cAntonio Valdes-Sosa, P., Nagarajan, S. S., Arnulfo, G., Horn, A., Blenkmann, A. O., Phillips, H. N., et al. (2017). iElectrodes: a comprehensive open-source toolbox for depth and subdural grid electrode localization. Front. Neuroinform. 11:10. 10.3389/fninf.2017.00010.\u201d It should be \u201cQin, C., Tan, Z., Pan, Y., Li, Y., Wang, L., Ren, L., et al. (2017). Automatic and precise localization and cortical labeling of subdural and depth intracranial electrodes. Front. Neuroinform. 11:10. 10.3389/fninf.2017.00010,\u201d with \u201cQin et al., Additionally, the reference for Jiang T. et al., 2017 was incorrectly written as \u201cJiang, T., Wang, J., Lin, J. J., Wang, L., Qin, C., Tan, Z., et al. (2017). Automatic and precise localization and cortical labeling of subdural and depth intracranial electrodes. The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Trypanosoma cruzi, the etiological agent of Chagas disease. Triatoma brasiliensis complex is a monophyletic group formed by two subspecies and six species: T. b. brasiliensis, T. b. macromelasoma, T. bahiensis, T. juazeirensis, T. lenti, T. melanica, T. petrocchiae and T. sherlocki. The specific status of several species grouped in the T. brasiliensis complex was confirmed from experimental crossing and analysis of reproductive barriers. Thus, we perform interspecific experimental crosses between T. lenti and other species and subspecies of the T. brasiliensis complex and perform morphological analysis of the gonads and cytogenetic analysis in the homeologous chromosomes of the hybrids of first generation (F1). Besides that, we rescue all the literature data associated with the study of reproductive barriers in this monophyletic complex of species and subspecies. For all crosses performed between T. b. brasiliensis, T. b. macromelasoma, T. juazeirensis and T. melanica with T. lenti, interspecific copulas occurred , hybrids were obtained, none of the male hybrids presented the phenomenon of gonadal dysgenesis and 100% pairing between the chromosomes homeologous of the hybrids was observed. Thus, we demonstrate that there are no pre-zygotic reproductive barriers installed between T. lenti and the species and subspecies of the T. brasiliensis complex. In addition, we demonstrate that the hybrids obtained between these crosses have high genomic compatibility and the absence of gonadal dysgenesis. These results point to reproductive compatibility between T. lenti and species and subspecies of the T. brasiliensis complex (confirming its inclusion in the complex) and lead us to suggest a possible recent diversification of the taxa of this monophyletic group.Triatomines are hematophagous insects of great epidemiological importance, since they are vectors of the protozoan Trypanosoma cruzi , the etiological agent of Chagas disease [Triatomines are hematophagous insects of great epidemiological importance, since they are vectors of the protozoan Chagas, 909 , T. bahT. lenti ), T. b. iliensis ) and T. iliensis ). Multidiliensis \u201323, bioliliensis , crossiniliensis , 25\u201329, iliensis , 31, isoiliensis , dispersiliensis , cytogeniliensis \u201338 and piliensis , 39\u201341 aalidated and the melanica ), alloweix, 2007 , as wellahiensis , demonstal. 2002 .Triatoma b. brasiliensis is one of the main Chagas disease vectors in the Northeast region of Brazil [T. juazeirensis was considered as a population of T. b. brasiliensis collected in Juazeiro, Bahia, Brazil [T. melanica, until 2006, was considered as a subspecies of T. b. brasiliensis [Triatoma petrocchiae is a species morphologically related to T. b. brasiliensis [Triatoma lenti and T. bahiensis were described, in 1967, as melanic forms of T. b. brasiliensis [T. bahiensis was considered synonymous with T. lenti [Triatoma lenti was notified in two Brazilian states, namely, Bahia and Goi\u00e1s [Triatoma sherlocki is an endemic species from Bahia [T. b. macromelasoma, described based on melanic forms of T. b. brasiliensis found at home in the state of Pernambuco [f Brazil , as it if Brazil \u201350. Thisf Brazil . Until 2, Brazil , being t, Brazil , 41. In iliensis endemic iliensis , 51. Triiliensis that is iliensis , 51. Triiliensis . For 37 T. lenti and, recT. lenti . Triatomnd Goi\u00e1s , 51, 53.om Bahia . Finallyrnambuco , 51, wasrnambuco .T. brasiliensis complex , foT. lenti and other species and subspecies of the T. brasiliensis complex and perform morphological analysis of the gonads and cytogenetic analysis in the homeologous chromosomes of the hybrids of first generation (F1) (with emphasis in the interspecific genomic compatibility). Besides that, we rescue all the literature data associated with the study of reproductive barriers in this monophyletic complex.Thus, taking into account that the study of experimental crosses and of the resulting hybrids can (a) help to understand the systematics of this vectors complex, (b) can be used to analyze the isolation mechanisms that limit gene flow between the different species, (c) as well as can be used to establish the role of natural hybridization in the generation of new variants (which can lead to adaptive evolution and/or the foundation of new evolutionary lineages) , 60, we T. b. brasiliensis, T. b. macromelasoma, T. juazeirensis and T. melanica with T. lenti , Araraquara, S\u00e3o Paulo, Brazil. These species and subspecies were identified with the help of the dichotomous keys developed by Costa et al. [Reciprocal experimental crosses were conducted between T. lenti to assesa et al. and Dalea et al. . The expa et al. and Menda et al. : the insT. brasiliensis complex were compiled , T. tibiamaculata and T. vitticeps with T. b. brasiliensis and confirmed that these species are unrelated to the T. brasiliensis complex .T. lenti and the species and subspecies of the T. brasiliensis complex confirms the inclusion of the species in the complex .For all crosses performed , interspa et al. confirmeT. b. brasiliensis and T. lenti (both directions) and the highest rates related to crosses between T. juazeirensis female and T. lenti male and between T. melanica and T. lenti (both directions). The only species of the T. brasiliensis complex that present genetic distance very close to the minimum stipulated to consider a species as valid are T. melanica and T. lenti [T. juazeirensis and T. lenti is higher than 10% [T. lenti and T. infestans [Although hybrids were obtained for all directions of the crosses , the hatT. lenti . Howeverthan 10% (close tnfestans which arnfestans and do nnfestans ).T. brasiliensis complex in the Caatinga biome, as well as the other complexes present in several biomes in the Latin America: T. rubrovaria in the Pampa, T. infestans in the Chaco and T. sordida, T. matogrossensis and part of T. maculata in the Cerrado. Triatoma b. brasiliensis when crossed with species of the T. sordida [T. infestans [T. vitticeps complexes [T. brasiliensis complex and suggested 5.2 Myr of independent evolution between these taxa. Considering the origin of Triatominae [T. brasiliensis complex.Patterson and Gaunt demonstratominae , the 5.2T. brasiliensis species and subspecies complex, through the degree of pairing of the homeologous chromosomes of the hybrids in metaphase I. The results obtained demonstrated 100% pairing between the chromosomes of the hybrids , we cyto hybrids .T. lenti and T. sherlocki and, as reported in the present study, also observed genomic compatibility between the species (100% pairing between homeologous chromosomes of the hybrids in metaphase I). Riley [T. brasiliensis complex present genetic distance to the Cyt B mitochondrial gene greater than 2% [Mendon\u00e7a et al. analyzed). Riley points o than 2% , 39, 40)T. brasiliensis complex share the same chromosomal characteristics [T. b. macromelasoma resulted from the natural crossing between T. b. brasiliensis and T. juazeirensis by the phenomenon of homoploidal hybridization. Recently, Costa et al. [T. b. brasiliensis and T. juazeirensis, which supports the origin of T. b. macromelasoma by homoploidal evolution. Natural hybridization events can be more common than previously thought: recently Antunes et al. [All species and subspecies of the eristics \u201338, 69. eristics suggestea et al. , throughs et al. demonstrT. b. macromelasoma is considered as an incipient species, the low interspecific genetic distance observed between T. b. macromelasoma, T. b. brasiliensis and T. juazeirensis [T. juazeirensis\u2013mainly in view of the recent catches of this species infected with T. cruzi in human dwellings [T. b. brasiliensis can be fixed in this species by introgression) and with its possible hybrids . The incompatibility of a pair of chromosomes was extremely important from a taxonomic point of view [T. brasiliensis complex by the pairing of 90% of the autosomes of these vectors.Alevi et al. observed of view . HoweverT. lenti and the species and subspecies of the T. brasiliensis complex. In addition, we demonstrate that the hybrids obtained between these crosses have high genomic compatibility (100% pairing between homeologous chromosomes) and the absence of gonadal dysgenesis. These results point to reproductive compatibility between T. lenti and species and subspecies of the T. brasiliensis complex (confirming their inclusion in the complex) and lead us to suggest a possible recent diversification of the taxa of this monophyletic group.Thus, we demonstrate that there are no pre-zygotic reproductive barriers installed between"} +{"text": "British Journal of Cancer 10.1038/s41416-021-01261-9, published online 15 March 2021Correction to: The original version of this article unfortunately contained a mistake in an author name. Elleke F. P. Peterse should be changed to Elisabeth F. P. Peterse. The authors apologize for the oversight. The original article has been corrected."} +{"text": "The authors wish to make the following erratum to this paper :youribroekhuizen@me.com (Y.C.B.B.); m.w.jaspers@amc.uva.nl (M.W.M.J.); their contributions: writing\u2014original draft: Y.C.B.B.; conceptualization, writing\u2014review and editing: M.W.M.J.The addition of authors Youri C. B. Broekhuizen and Monique W. M. Jaspers due to an omission. Additionally, their affiliation and emails: Center of Human Factors Engineering of Health Information Technology (HIT-Lab), Institute of Biomedical Informatics, Amsterdam Public Health Research Institute\u2014Location Academic Medical Center (AMC), University of Amsterdam (UvA), 1012 WX Amsterdam, The Netherlands; The authors would like to apologize for any inconvenience caused to the readers by these changes."} +{"text": "About one-third of the world\u2019s barley crop is used for malt production to meet the needs of the brewingindustry. In this regard, the study of the genetic basis of malting quality traits and the breeding of malting barleyvarieties that are adaptive to their growing conditions are relevant throughout the world, particularly in the Russian Federation, where the cultivation and use of foreign malting varieties of barley prevails. The main parametersof malting quality are malt extract, diastatic power, Kolbach index,viscosity, grain protein, wort \u03b2-glucan, free amino nitrogen, and soluble protein content. Most of these componentsare under the control of quantitative trait loci (QTLs) and are affected by environmental conditions, which complicates their study and precise localization. In addition, the phenotypic assessment of malting quality traits requireselaborate, expensive phenotypic analyses. Currently, there are more than 200 QTLs associated with malting parameters, which were identified using biparental mapping populations. Molecular markers are widely used both formapping QTL loci responsible for malting quality traits and for performing marker-assisted selection (MAS), which,in combination with conventional breeding, makes it possible to create effective strategies aimed at acceleratingthe process of obtaining new promising genotypes. Nevertheless, the MAS of malting quality traits faces a series ofdifficulties, such as the low accuracy of localization of QTLs, their ineffectiveness when transferred to another genetic background, and linkage with undesirable traits, which makes it necessary to validate QTLs and the molecularmarkers linked to them. This review presents the results of studies that used MAS to improve the malting quality ofbarley, and it also considers studies that searched for associations between genotype and phenotype, carried outusing GWAS (genome-wide association study) approaches based on the latest achievements of high-throughputgenotyping (diversity array technology (DArT) and single-nucleotide polymorphism markers (SNPs)). It is used for feed, food,and malting. About 30 % of the barley is processed into malt,mainly used for brewing beer affect the quality of malt . The quality of malt is mainly determined by the optimalvalues of malt extract , diastatic power (the abilityof enzymes to hydrolyze starch to simple sugars), viscosity, contentof \u03b2-glucan in the wort, Kolbach index , and contents of free amino nitrogen, soluble protein,and protein in the grain .At the same time, it is necessary that the grain is of a suitablemalting variety, has a high germinating capacity and energy,is sensitive to water absorption, does not have impurities, anddoes not contain microbial or chemical pollutants .http://www.ukmalt.com/press-release-update-november-2019; https://ambainc.org/amba-publications/recommended-maltingbarley-varieties/).In general, the main breeding goal is the development ofbarley varieties with high malting quality and increased yield. Maintaining a balancebetween these two parameters is a serious problem, since highyields, often dependent on the use of nitrogen fertilizers, areassociated with high protein and \u03b2-glucan content, which isundesirable for high-quality malt . Froma breeding point of view, there is no single barley ideotypeuniversally accepted as describing a malting variety. Earlier,it was reported that two-row barleys were used for malting allover the world, except in the United States of America (USA)and Mexico, where six-row varieties were mainly used . The best malting varieties have a spring growthhabit. However, due to the depletion of their genetic diversity, as well as climatechange, interest in winter varieties has increased, and thebrewing associations of Europe and the USA have includedthem in the list of recommended malting varieties (http://www.fao.org/faostat/ru/). However,breeding of malting barley in Russia has not been particularlydeveloped; as a result, 80\u201390 % of malt is produced fromimported raw materials or when growing foreign maltingvarieties . The breeding andcultivation of Russian malting barley varieties in the RussianFederation is carried out both in the European region and inWestern Siberia and Altai . Due tostrict standards of the brewing industry and different climaticconditions in the various regions of the Russian Federation,the development of a raw material base for malting barleyfaces significant difficulties . As a rule, foreign varieties have good technologicalcharacteristics that meet the requirements of brewing production; however, when grown in Russian regions, the parametersof malt and beer produced from them often do not reach thedeclared characteristics . In this regard, the development of competitivelocal varieties of malting barley that combine adaptability togrowing conditions with optimal technological parameters isan important goal.The Russian Federation ranks first in worldwide production of barley and in areas featuring this crop , which makes itdifficult to study them using conventional methods of analysis.The use of molecular markers makes it possible to significantlyexpand the possibilities for chromosomal localization of genesand QTLs (quantitative trait loci) that determine malt qualitycharacteristics and provide breeders with an effective toolfor accelerated and directed plant selection (marker-assistedselection) . This review examines and discusses the main problemsassociated with molecular genetic mapping of malting qualitytraits, as well as the results of using recent high-throughputgenotyping technologies for applied research to obtain breeding material with improved malting characteristics.The phenotype that determines the malting quality of barley isthe result of interactions among a large number of components,each of which shows a complex inheritance . Most of them are quantitative traitswith a comparatively low heritability, which are controlledby multiple genes . For example, the meanheritability for malt extract assessed in the F2 and F3 generations using different methods and populations ranged from 8 to 70 %, whereas the heritability of \u03b1-amylase activity inF2 and F5 plants ranged from 37 to 65% and from 39 to 74 %,respectively . In addition, the phenotypicvariation of quantitative traits often depends on growingconditions, such as soil composition, temperature, irrigation,fertilizer application , genotype\u00d7environment interactions , methods of laboratoryanalysis , and complex relationships amongcomponents that determine malting quality. All these aspectsmake it difficult to accurately localize the QTLs that controlmalting quality traits.In some studies, QTLs for certain malting quality traitswere found in different regions of the genome, due to theinfluence of different genotypes used in cross populationsand/or the influence of genotype\u00d7environment interactions.For example, QTLs controlling the content of malt extractwere identified on chromosomes 1H and 2H in populationsderived from two North American varieties and on chromosomes 1H and 5H in populationsfrom Australian and Canadian varieties .Even when using the same population (Blenheim\u00d7E224/3),QTLs for malt extract on chromosome 2H were found by different researchers in different amounts and positions . This makes it necessary tovalidate QTLs using different mapping populations grownunder different conditions in order to assess their interactionwith the environment . However, QTL analysis based on biparental mapping populations has been widely used to identify and localize QTLs. QTLs or genes controlling malting traits wereidentified on all seven barley chromosomes, but most wereidentified on chromosomes 1H, 4H, 5H, and 7H . Many studies investigating QTLs related to malting quality were based on genotypingdata obtained using various molecular markers . In addition, the database ofbarley markers has significantly expanded with the development of methods for detecting SNPs (single-nucleotide polymorphisms) using Illumina GoldenGate technology, whichprovided access to thousands of alleles and led to the creationof a high-density consensus genetic map of barley containing2943 SNP loci . Information about theseSNPs was combined with other genetic markers such as RFLP,AFLP, SSR, and diversity array technology (DArT) in the integrated barley malting QTL database . Asa result, a map was compiled with 154 QTLs associated with18 malting quality traits localized on all barley chromosomes.At least 268 malting QTLs/genes are known to have beenidentified in more than 20 mapping populations . However, the resultsof these studies are difficult to directly apply to breeding formany reasons. For example, most mapping populations do notinclude genotypes used to produce new varieties, QTLs maybe specific to a particular population, alleles desirable for malting quality may only be fixed in certain genotypes, and some QTLs may have low localization accuracy due to the smallsize of mapping populations . A particular problem for breeding is that QTLs identified in mappingpopulations may not segregate in breeding populations, suchas QTLs for malting quality traits on barley chromosomes 4Hand 7H . In this regard, it is emphasizedthat the use of local breeding lines for mapping can be moreeffective in identifying QTLs that are adequate to specificgrowing conditions and breeding goals .The marker-assisted selection (MAS) of barley is of particularinterest in terms of developing genotypes with good maltingquality, since the phenotypic evaluation of malting qualitycharacteristics using laboratory equipment is an expensiveprocess and requires large amounts of grain. In addition, thesetraits are affected by the interaction of the genotype with theenvironment. Molecular markers for assessing malting qualitytraits can provide rapid selection of plants at the early stagesof breeding through a study of large populations, therebyincreasing the likelihood of detecting the desired geneticcombinations .Marker-assisted selection for quantitative traits, which include malting quality traits, has two main limitations. First,in comparison with monogenic traits, quantitative traits arecharacterized by low heritability, which leads to a less accurateassessment of their genetic localization. As a result, it is necessary to select a large fragment of the chromosome, which isassociated with the transfer of many potentially undesirablegenes. Second, many of the QTL alleles are difficult to detectwhen transferred to a different genetic background . Most studies on QTL mapping for malting qualitytraits were based on crosses of parents contrasting in maltingtraits, for example, malting variety\u00d7feed variety, which goesagainst the common breeding practice for malting barley,whereby feed genotypes are not typically used. In this regard,QTLs for malting quality traits should be verified in breeding programs before being used in marker-assisted selection.In addition, some of the identified QTLs cannot be used inMAS since they are associated not only with target traits, butalso with undesirable ones. For example, one of these QTLsfound on the long arm of chromosome 3H was associatednot only with an increase in diastatic power, but also with anincrease in viscosity .1 presents adescription of the markers used in MAS for barley maltingcharacteristics.One successful example of improving malting qualityusing MAS is the work related to the enzyme \u03b2-amylase,which mainly determines the diastatic power . The Bmyl locus on chromosome 4H controls \u03b2-amylaseactivity, free/bound enzyme ratio, and thermal stability, andits alleles are different isoenzyme types. PCR markers havebeen developed that allow selection of different alleles of\u03b2-amylase, which allows the use of these markers in MASdepending on the needs of the brewing industry . For example, if high diastatic power and enzymaticactivity are required, the Sd2-H and Sd3 alleles should beselected. Using molecular markers and double-haploid technology, the Bmy1-Sd3 allele from Hordeum spontaneum L.was transferred to two commercial barley varieties. As a result, the activity of \u03b2-amylase and, thus, the diastatic power in thesevarieties increased by an average of 30 % .The use of the CAPS marker made it possible to transfer theSd3 allele of the thermostable \u03b2-amylase from wild barley(H. spontaneum) into a commercial barley (variety Gairdner)and obtain elite lines with high malting quality characteristics . Supplementary materialhttps://vavilov.elpub.ru/jour/manager/files/SupplTrubacheeva_Engl.pdfSupplementary Materials are available in the online version of the paper:Cultivated barley contains two isoforms of the enzymelipoxygenase, which oxidizes unsaturated fatty acids to thecorresponding hydroxyperoxides. One of the isoforms, LOX1,promotes the synthesis of substances that impair the flavorstability of beer . It was found that this traitis encoded by a locus on chromosome 4H, and the absenceof this protein is caused by a single-nucleotide mutation. Theuse of the CAPS marker for the selection of mutants lackingthis protein made it possible to develop new breeding lines inthree years, despite this process usually taking approximatelyten years. Beers made with barley lacking LOX1 (null-Loxvariety) were found to have a 75 % reduction in the contentof substances that cause a stale flavor due to oxidation compared to beer made from ordinary barley malt . One of the indicators of beer quality is the stability ofbeer foam, which depends on the combined action of variousproteins, iso-alpha acids, polysaccharides, and metal ionscontained in beer. To select haplotypes of Z4 and Z7 proteinsassociated with the quality of beer foam, CAPS markers weredeveloped, and their efficiency was shown in the analysis of23 malting barley varieties .The possibility of using MAS to select populations withimproved malting quality has been shown . For example, it was found that lines carrying an allele linked to SSR marker EBmac501 on chromosome 1Hwere characterized by increased diastatic power, as well as\u03b2-amylase and \u03b1-amylase activities, compared to other lines.In addition, this marker locus was associated with an increasedcontent of malt extract and, therefore, was considered promising for use in MAS . The use of MAS forthe selection of plants carrying the target malting quality traitsmade it possible to develop promising breeding lines whencrossing feed barley Keel with three donor varieties with highmalting quality characteristics . F. Hanet al. (1997) compared the efficiency of malting quality traitselection using phenotypic assessment and marker-assistedselection using molecular markers flanking the QTL1 andQTL2 genome regions for malt extract, \u03b1-amylase activity,diastatic power, and \u03b2-glucan content. It was shown that, forQTL1, the combination of MAS and phenotype assessmentwas more effective than phenotypic selection only, whichinvolves laborious and expensive procedures. The selection ofdesired genotypes can be greatly facilitated using PCR markers; therefore, a number of RFLP markers for malting QTLshave been converted to PCR markers .A number of other examples of the use of MAS to identifyQTLs associated with malting quality traits are also known.For example, the localization of two QTLs affecting malting quality traits on chromosome 5H was confirmed using molecular markers. Later, the selection of genotypes carrying allelesfrom the malting variety Harrington made it possible to obtaindouble-haploid lines with improved malting characteristics,such as low \u03b2-glucan values and protein content in grain, highdiastatic power, and high malt extract .The use of PCR markers for the QTL region on chromosome5H affecting \u03b1-amylase activity made it possible to introgressthis trait from the malting barley variety Morex to the feedbarley Labelle . In addition, this studyshowed that MAS can be successfully applied to incorporateQTLs into populations where only one of the parents (theMorex variety) was used for the initial QTL identification andmapping. Using SSR markers, the QTL regions for proteincontent, malt extract, and viscosity were introgressed from thewinter malting barley Nure to the double-haploid populationobtained from crossing Nure with the spring malting varietyTremois . SSR markers flanking QTLs onchromosomes 2H, 6H, and 7H were developed. These loci hada significant effect on protein content and, according to theauthors, may be useful in the development of varieties with ahigh protein content . Using the populationsobtained by crossing elite malting barley varieties, QTLs formalting quality traits were mapped, and two SSR markerspromising for use in MAS were identified . The emergence of more cost-effective, high-throughput genotyping platforms such as diversity array technology (DArT) and Illumina\u2019s GoldenGate assay , as well as improvements in statistical methodologyand computer programs, has enabled genome-wide association studies (GWAS) to be a promising alternative approachto conventional QTL analysis of biparental populations forthe detection and accurate mapping of quantitative trait loci.The advantages of this method include a wider coverage ofthe genetic diversity of the population, i. e., simultaneousstudy of a large number of alleles, high-resolution mapping,establishment of single-nucleotide polymorphisms, and reduced study time due to the absence of the need to develop amapping population . For the effective use of available technologies, a numberof researchers used information obtained during long-termbreeding trials when performing GWAS, which significantlyreduced the cost of genetic research. For example, data onmalting quality traits from 97 breeding trials conducted on1862 lines were combined with the results of using 3072 SNPmarkers for association mapping. This approach was found toprovide improved accuracy for identifying QTLs associatedwith malting quality traits compared to previous mappingstudies . In addition, the GWASmethod can identify a much larger number of molecularmarkers compared to traditional QTL mapping . In another study, phenotypic data of 18 malting traitsaccumulated over 25 years for 174 European barley varietieswere used in the study of GWAS using DArT markers. In addition to confirming the already known QTLs on chromosomes 1H, 2H, and 5H, new associations were found, forexample, markers linked to the malting quality and viscosity. A collection of 91 elite malting barleylines was analyzed using association mapping to identify DArTmarkers associated with seven malting traits, and 19 putativecandidate expressed sequence tags responsible for marker-traitassociations were identified . The studyof a collection of 224 spring barleys using 1536 SNPs madeit possible to detect 57 novel QTLs responsible for agronomicvaluable traits, including starch and protein content . Thus, the associations between genotype andphenotype identified in the studies reviewed may be usefulfor selecting parent genotypes carrying the desired alleles inorder to model future breeding studies, although the resultsobtained need to be validated in the field.The malting quality of barley is the result of a complex interaction of various components controlled by multiple genes. Inthis regard, selection based on phenotypic characteristics isa time-consuming and expensive process. Marker-associatedselection of malting quality traits is an effective alternative orcomplement to conventional breeding, but requires detailedinformation about genes/QTLs responsible for the target traits.QTL analysis is widely used for the chromosomal localizationof agronomic traits and the detection of molecular markers.To date, a large number of QTLs have been identified thatcontrol malting quality traits, and the use of associated molecular markers and recent advances in molecular tools forhigh-resolution genotyping make it possible to effectivelyselect the desired genotypes for breeding barley varieties withhigh malting quality characteristics.The authors declare no conflict of interest.Anis\u2019kov N.I., Nikolaev P.N., Popolzukhin P.V., Safonova I.V., Bratseva L.I. A new middle-ripening spring malting barley varietyOmskiy 100. Vestnik Altayskogo Gosudarstvennogo AgrarnogoUniversiteta = Bulletin of Altai State Agricultural University. 2016;4(138):14-19. 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There is no doubt that analysis of new and practically important compounds should be carried out within the framework of theoretical and experimental methods combination. The well-established computational codes 2+ structural units were obtained theoretically, and corresponding spectral bands were observed in vibrational spectra. Ribeiro-Claro P.J.A. et al. [The first paper written by Oreshonkov A.S. et al. is aimed. et al. demonstr. et al. used an . et al. . The ind. et al. is devot. et al. investig"} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-021-81250-3, published online 21 January 2021Correction to: In the original version of this Article Florentina Cojocaru and Tudor \u0218elescu were omitted as equally contributing authors. In addition, the Author Contributions section in this Article was incorrect.\u201cF.C. performed the cell cultures, migration experiments, siRNA and data analysis. G.C performed Western blotting. T.S. performed patch-clamp and data analysis. D.D. performed the microfluorimetry experiments. D.M. and A.B. analysed and interpreted the data. L.M. performed the cell cycle experiments. R.C performed qRT-PCR experiments. S.D provided PDAC and HPDE cell lines ann interpreted qRT-PCR experiments. F.C., T.S., D.C. and A.B. analysed the data and wrote the manuscript. All authors read and approved the final version of the manuscript.\u201dnow reads:\"Florentina Cojocaru and Tudor Selescu contributed equally and are considered first authors in this publication. F.C. performed the cell cultures, migration experiments, siRNA and data analysis. T.S. performed microfluorimetry experiments, patch-clamp recordings and data analysis. D.D. performed microfluorimetry experiments. L.M. performed the cell cycle experiments. G.C. performed Western blotting. N.R.C. performed qRT-PCR experiments. S.D. provided the PDAC and HPDE cell lines and interpreted qRT-PCR experiments. D.M. and A.B. analyzed and interpreted the data. F.C., T.S., D.C. and A.B. analyzed the data and wrote the manuscript. All authors read and approved the final version of the manuscript.\"The original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-021-92554-9, published online 28 June 2021Correction to: Sunayana Kapil was omitted from the author list in the original version of this Article.The Author Contributions section now reads:7 and 8, S.K. prepared compounds 28A and 28B, and R.T. prepared all other chemical intermediates. T.D.J. completed kinetics and X-ray studies. All authors wrote their respective portions of the main manuscript text, supporting information text, and figures. D.D.R. and S.J.S. conceived and directed the structural biology and chemistry, respectively, and edited the manuscript. All authors reviewed the manuscript.A.S. prepared compounds The original Article has been corrected."} +{"text": "C. elegans. microPublication Biology. 10.17912/micropub.biology.000397. Erratum in: microPublication Biology. 10.17912/micropub.biology.000466.Cohen, SM; Sun, JJ; Schroeder, FC; Sternberg, PW (2021). Transcriptional Response to a Dauer-Inducing Ascaroside Cocktail in Late L1 in The links to extended data files were omitted from the original article, this has been corrected. Links to the extended data files Cohen2021_N2_Ascr_extended and Cohen2021_daf-22_Ascr_extended have been attached to the original article."} +{"text": "J. Sport Health Sci. 9, 103\u2013104. doi: 10.1016/j.jshs.2020.02.001.\u201d It should be \u201cChen, P., Mao, L., Nassis, G. P., Harmer, P., Ainsworth, B. E., and Li, F. (2020). Coronavirus disease (COVID-19): The need to maintain regular physical activity while taking precautions. J. Sport Health Sci. 9, 103\u2013104. doi: 10.1016/j.jshs.2020.02.001.\u201dIn the original article, the reference for Chen et al. was incoThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-022-08134-y, published online 12 March 2022Correction to: The original version of this Article contained an error in Affiliation 5, which was incorrectly given as \u2018K.A.CARE Energy Research & Innovation Center, King Fahd University of Petroleum and Mineral, Dhahran, Saudi Arabia\u2019. The correct affiliation is listed below.K.A.CARE Energy Research & Innovation Center at Dhahran, Saudi Arabia.The original Article has been corrected."} +{"text": "J. Sport Health Sci. 9, 103\u2013104. doi: 10.1016/j.jshs.2020.02.001\u201d. It should be \u201cChen, P., Mao, L., Nassis, G. P., Harmer, P., Ainsworth, B. E., and Li, F. (2020). Coronavirus disease (COVID-19): The need to maintain regular physical activity while taking precautions. J. Sport Health Sci. 9, 103\u2013104. doi: 10.1016/j.jshs.2020.02.001\u201d.In the original article, the reference for Chen et al. (2009) was incorrectly written as \u201cChen, P., Mao, L., Nassis, G. P., Harmer, P., Ainsworth, B. E., and Li, F. (2009). Wuhan coronavirus (2019-nCoV): the need to maintain regular physical activity while taking precautions. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "TEX19) is a specific human stem cell gene identified as cancer\u2010testis antigen (CTA), which emerged as a potential therapeutic drug target. TEX19.1, a mouse paralog of human TEX19, can interact with LINE\u20101 retrotransposable element ORF1 protein (LIRE1) and subsequently restrict mobilization of LINE\u20101 elements in the genome.Testis expressed 19 of Outcomes of this study revealed amino acids that potentially stabilize the predicted interaction interface between TEX19 and LIRE1. Of these SNPs, 37 were predicted to play a probably damaging role for the protein, three of them located at the binding site of LIRE1 and could disturb this binding affinity.This information can be verified by further in vitro and in vivo experimentations and could be exploited for potential therapeutic targets. interaction pattern between TEX19 and LIRE1 proteins Formation of Van der Waals, electrostatic interactions and hydrogen bonding and formation of TEX19 and LIRE1complex The 3D structure of TEX19 protein was predicted by using the Iterative\u2010Threading ASSEmbly Refinement (I\u2010TASSER) server software for possible damaging effect on the protein. Sorting Tolerant From the Intolerant (SIFT) server was used for the prediction of the deleterious effect of mutations. For the prediction of disease\u2010related SNPs, we used Predictor of human Deleterious Single\u2010Nucleotide Polymorphisms (PhD\u2010SNP), and SNPs&GO servers. Project HOPE webserver was used to analyze the effect of single point mutation on protein structure.Different software were used for prediction of the effect of missense single nucleotide polymorphisms (SNPs) on the structure and function of the 2.5ConSerfserver. BioEdit version 2.7.5 and was then validated by PROSA statistic analysis not only reflects the change of protein backbone versus simulation time but also indicates the divergence of the structure. The RMSD of the complex became stable at 15\u00a0ns. The RMSD value of modeled helicase was 0.45\u00a0nm Figure . The val3.4Table 3.5Residues of TEX19 showing hydrogen bonds with LIRE1 were among conserved sequences. Phe35 of TEX19 which have an interaction with LIRE1 predicted among highly conserved buried residues Figures and 5.4In silico methods such as docking and molecular dynamic (MD) simulations are used to find the correct conformation of a ligand and its receptor and have been used previously in drug design (Bissaro et al., The authors have declared no conflict of interest.Conceptualization, O.R.A, F.A., and Y.H.; methodology, F.A., Y.H., H.A., and N.A.; software, Y.H., H.A., and N.A.; validation, F.A., Y.H., H.A., and N.A.; formal analysis, Y.H., H.E.A., and N.A.; investigation, Y.H., H.A., L.M., S.A., and N.A.; resources, F.A., Y.H., H.A., and N.A.; data curation, F.A., Y.H., H.A., L.M., and N.A.; writing\u2014original draft preparation, O.M.A., F.A., and Y.H.; writing\u2014review and editing, F.A., Y.H., H.A., S.A., L.M., N.A.,O.R.A., H.E.A., and O.M.A.; funding acquisition, F.A., N.A., S.A., and O.R.A."} +{"text": "Carcharodus H\u00fcbner, [1819] and its close relatives. Type species of all available genus-group names were sequenced. We find that species attributed to four exclusively Old World genera form a monophyletic group that we call a subtribe Carcharodina Verity, 1940. In the phylogenetic trees built from various genomic regions, these species form 7 (not 4) groups that we treat as genera. We find that Muschampia Tutt, 1906 is not monophyletic, and the 5th group is formed by currently monotypic genus Favria Tutt, 1906 new status , which is sister to Gomalia. The 6th and 7th groups are composed of mostly African species presently placed in Spialia. These groups do not have names and are described here as Pyrgus colotes Druce, 1875) and Agyllia Grishin, gen. n. . Two subgroups are recognized in Ernsta: the nominal subgenus and a new one: Delaga Grishin, subgen. n. . Next, we observe that Carcharodus is not monophyletic, and species formerly placed in subgenera Reverdinus Ragusa, 1919 and Lavatheria Verity, 1940 are here transferred to Muschampia. Furthermore, due to differences in male genitalia or DNA sequences, we reinstateGomalia albofasciata Moore, 1879 and Gomalia jeanneli as species, not subspecies or synonyms of Gomalia elma , and Spialia bifida as a species, not subspecies of Spialia zebra . Sequencing of the type specimens reveals 2.2\u20133.2% difference in COI barcodes, the evidence that combined with wing pattern differences suggests a new status of a species for Spialia lugens and Spialia carnea , formerly subspecies of Spialia orbifer .We obtained whole genome shotgun sequences and phylogenetically analyzed protein-coding regions of representative skipper butterflies from the genus Alenia Evans, 1935 belongs to the tribe Celaenorrhinini Swinhoe, 1912. Old World Spialia Swinhoe, 1912 and Muschampia Tutt, 1906 are placed in the tribe Carcharodini Verity, 1940. Holarctic Pyrgus H\u00fcbner, [1819] with its New World relatives Burnsius Grishin, 2019, Chirgus Grishin, 2019 and Heliopetes (Heliopyrgus) americanus are from the tribe Pyrgini Burmeister, 1878. These 5 genera and one species are more similar to each other in appearance than to their closest relatives. Moreover, some species of Muschampia are more marbled than checkered and their patterns indeed remind of Carcharodus H\u00fcbner, [1819], the nominal genus of their tribe.Checkered, grizzled and marbled wing patterns are present in a number of Hesperiidae species from around the world , 1953. PSpialia, Gomalia Moore, 1879, Carcharodus and Muschampia that we unite in a subtribe Carcharodina Verity, 1940. These genera have received significant attention in literature pale spots (if present) near forewing apex and in the discal cell. Spialia and Muschampia are white-spotted and the spots are opaque. Hindwing is crenulate in Carcharodus and Muschampia, but more evenly rounded in Spialia and Gomalia. The outer hindwing margin is somewhat wavy and produced at vein 1A+2A in Gomalia, which also differs from the other three genera by uncheckered (or indistinctly checkered) fringes. Furthermore, Spialia differs from Muschampia by the central pale spot in discal cell on dorsal forewing positioned before the origin of vein CuA1 and the pale spot in space CuA1-CuA2 being in the middle between the discal cell spot and the spot in cell M3-CuA1, or closer to the latter. In Muschampia, the central pale spot in discal cell on dorsal forewing is usually centered around the origin of vein CuA1, and if not, then it overlaps with the CuA1-CuA2 cell spot, which is closer to the discal cell spot than to the spot in M3-CuA1 cell. This relative simplicity in the genus identification based purely on appearance undoubtedly contributed to the widespread use of Carcharodina classification into these four genera. However, significant variation in genitalic morphology within Carcharodus and Spialia has been documented and type species of its genus, which in turn is the type genus of its tribe, Euphorbiaceae were recently discovered as foodplants , which is not monophyletic with Muschampia and instead forms a monotypic genus sister to Gomalia. Moreover, wing pattern similarities confused researchers who placed in Carcharodus a number of species that actually belong to Muschampia. Here, we correct these problems and some others.To better understand phylogenetic relationships and taxonomy of Carcharodina\u2014a challenge from purely morphological perspective\u2014we obtained and analyzed whole genome shotgun DNA sequence reads of representative species, including several primary type specimens . The resSpialia , and uniSpialia, Gomalia, Carcharodus and Muschampia including representatives of all available genus group names. In addition, we used 8 species from 5 closely related genera as outgroups. One specimen per species was included in the analysis , leaving the leg intact. About 70% of DNA was used to construct mate-pair libraries according to our published protocols (DNA was extracted from legs (and abdomens) non-destructively using Macherey-Nagel (MN) reagents. 70 \u03bcl buffer T1 and 10 \u03bcl protK were simply added to the tube without crushing the leg, and the mixture was incubated at 57\u00b0C for 24 hours. Then, 80 \u03bcl buffer B3 was added and incubation continued for 2 hours, after which 85 \u03bcl of absolute EtOH was added and thoroughly mixed. The resulting liquid was transferred to a different tube and DNA extraction continued according to MN protocol we have obtained previously . Second, instead of splitting into 4 clades according to the original genus names, the group forms 7 clades shown in different colors in Spialia is split into 3 clades, two of which are not even sisters in the COI barcode dendrogram. The separation between the three clades suggests that they represent three genera, two of which do not have names and are described here. In addition, one of these clades partitions into two subclades, one of which is described as a subgenus. Description of these three new taxa follows.First, species placed in the 4 Old World genera http://zoobank.org/8301DAE5-F4D8-4EE8-BFDC-BFF4BCE2A8E9Pyrgus colotes Druce, 1875 , or thesis 11 in colotes, delagoae, and dromus species groups. Differs from its relatives by the following characters. Ventral hindwing with straight median white band not separated into sports, i.e., white spot in cell RS-M1 (space 6) joins central spot to the outer (and not inner) spot in cell Sc+R1-RS (space 7), but in many species of Spialia this band either broken into spots or directed basad at costa. While Spialia species lack costal fold in males, some Ernsta species have costal fold (colotes species group). Species with costal fold are in addition characterized by the central white discal cell spot on dorsal forewing not closer to discocellular spot than to the basal cell spot and no two white spots are present above over the central cell spot (to distinguish from asterodia species group of Ernsta) and hindwing submarginal pale spots in cells M1-M2 & M2-M3 (spaces 4 & 5) offset basad from the rest of the submarginal spots. Species without costal fold either lack the basal white spots in discal cell on dorsal forewing, however, some white scales along cubital vein may be present forming a narrow streak (the delagoae species group), or on dorsal forewing in CuA2-1A+2A cell (space 1B) the outer lower median spot absent and inner lower median spot not smaller than the outer upper median spot (dromus species group). In male genitalia, uncus not deeply incised, gnathos dorsally joined to tegumen, if gnathos free (in some species from the delagoae group), then coecum of aedeagus shortened or absent. In DNA COI barcode region, a combination of the following base pairs is diagnostic: A46T, C278T, T280A, T282T (not C), T301T (not C), T349A, G353G (not T), A481A (not T or C), and 529(not T).Morphologically similar to The name is a feminine noun in the nominative singular. It honors Ernst Brockmann of Lich, Germany and his unstoppable passion for Hesperiidae in general and the Grizzled skippers in particular. Without his enthusiasm, help, encouragement and specimens this study would not be accomplished.delagoae, colotes, and dromus species groups, as they were defined by E. colotes, E. mangana, and E. bifida) cross the Red Sea into the southern corner of the Arabian Peninsula, and one (E. zebra) is recorded from the northwestern Himalayas.Encompasses The phylogenetic trees suggest http://zoobank.org/A5431ACA-C253-4414-AE23-97A320D45D4DPyrgus delagoae Trimen, 1898 absent, and the spot at the base of the discal cell is absent in most species . Ventral hindwing with a straight median white band, i.e., a white spot in cell RS-M1 (space 6) joins the central spot to the outer (and not inner) spot in cell Sc+R1-RS (space 7). In male genitalia, coecum of aedeagus shortened or absent; valva with the costal process and harpe (=cucullus) lacks a fold covering the costal process, or the fold is small. In DNA COI barcode region, a combination of the following base pairs is diagnostic: T19A, T22A, T70A, T374G, and T646C.Keys to 15 in The name is a feminine noun in the nominative singular derived from the name of the type species.delagoae species groups, as it was defined by Encompasses Ernsta, the phylogenetic trees closer to streak-like spot at distal end of cell than to well-developed and rounded basal spot; no dorsal white spots at base of CuA2-1A+2A cell (space 1B). Ventral hindwing with a straight median white band, i.e., a white spot in cell Rs-M1 (space 6) joins the central spot to the outer (and not inner) spot in cell Sc+R1-Rs (space 7). In male genitalia, uncus deeply incised; valva with large costal process and harpe (=cucullus) lacks a fold covering the costal process. In DNA COI barcode region, a combination of the following base pairs is diagnostic: A307T, A352T, T364C, C401T, T403A, T500C, and A502T.Keys to 2 in The name is a feminine noun in the nominative singular derived from the name of the type species.asterodia species groups as it was defined by Encompasses Carcharodus is not monophyletic. Only one species, Carcharodus tripolina groups with the type species of the genus Carcharodus alceae . These results are consistent with the recent treatment by Carcharodus species in Reverdinus Ragusa, 1919. In our trees, Reverdinus is in the same cluster with Muschampia Tutt, 1906 and the branch length separating Reverdinus from other Muschampia is not significantly larger than the branch lengths separating Muschampia species from each other. Thus, we consider Reverdinus Ragusa, 1919 to be a subgenus of Muschampia. Additionally, we see that genus names previously given to various groups currently placed in Muschampia indeed denote monophyletic groups within the genus and we suggest to treat these groups as subgenera: Warrenohesperia Strand, 1928, Sloperia Tutt, 1906 and Tuttia Warren, 1926 , the type species of the genus Favria Tutt, 1906 is not monophyletic with Muschampia. Instead, it is a confident sister of Gomalia in nuclear genome trees as currently considered, but a Gomalia species well removed from it. COI barcodes of the two species differ by nearly 7% (45 base pairs). Moreover, the differences in genitalia of the Indian Gomalia elma albofasciata Moore, 1879 and Spialia carnea formerly considered subspecies of Spialia orbifer . Sequencing of S. lugens and S. carnea type specimens in the Berlin Museum f\u00fcr Naturkunde reveals 2.2%\u22123.2% difference in COI barcode from nominotypical populations of S. orbifer. Distinct barcodes combined with the differences in facies suggest species-level status for these taxa. Spialia lugens differs from the two other species by the larger size, darker wing above with faint or absent submarginal sports, rarely, and mostly in females, better developed , a species distinct from Ernsta zebra and not its subspecies. Taken together, the data we obtained suggest the following taxonomic arrangement of the subtribe Carcharodina.Finally, difference in male genitalia, notably the shape of uncus , suggestBased on our analysis, the list of species arranged into genera and subgenera is given below. Synonymic names are included for genera and subgenera. Names treated as synonyms (genera and names of type species that are considered to be synonyms) are preceded by \u201c=\u201d: not followed by daggers are subjective junior synonyms; \u2020 objective junior synonyms; \u2021 unavailable names (such as homonyms and nomina nuda); \u201cpreocc.\u201d indicates preoccupied, the taxonomic order of the senior name is shown in brackets. Synonyms are attributed to subgenera. Type species (TS) for genera and subgenera are listed and underlined. For type species that are considered to be synonyms, valid names are shown in parenthesis. For valid genera and subgenera (not their synonyms), names of the type species or names which type species are considered to be synonyms of, are underlined in the list. Subspecies names are not listed pending further studies.Spialia Swinhoe, 1912; TS: galba FabriciusSubgenus Powellia Tutt, 1906 ; TS: =\u2021sao H\u00fcbner, 1800 (sertorius Hoffmansegg)=\u2021Neospialia Ko\u00e7ak, 1989; TS: =\u2021sao H\u00fcbner, 1800 (sertorius Hoffmansegg)=Spialia mafa Spialiagalba Spialia spio Spialia ali Oberth\u00fcr, 1881Spialia therapne Spialia sertorius Spialia rosae Hern\u00e1ndez-Rold\u00e1n, Dapporto, Dinc\u0103, Vicente & Vila, 2016Spialia orbifer Spialia lugens ; new status, was a subspecies of S. orbiferSpialia carnea ; new status, was a subspecies of S. orbiferPlatygnathia Picard, 1948; stat. rev., was a synonym of Spialia; TS: phlomidis Herrich-Sch\u00e4fferSubgenus Spialiaphlomidis Spialia struvei Spialia fetidaZhdanko, 1992Spialia irida Zhdanko, 1993Spialia osthelderi Spialia geron Spialia doris Spialia diomus Spialia ferax Agyllia asterodia ; new combination, was in SpialiaAgylliaagylla ; new combination, was in SpialiaAgyllia kituina ; new combination, was in SpialiaDelaga Grishin, new subgenus; TS: delagoae TrimenSubgenus Ernsta mangana ; new combination, was in SpialiaErnsta nanus ; new combination, was in SpialiaErnsta delagoae ; new combination, was in SpialiaErnsta zebra ; new combination, was in SpialiaErnsta bifida ; new combination, reinstated status, was a subspecies of Spialia zebraErnsta sataspes ; new combination, was in SpialiaErnsta depauperata ; new combination, was in SpialiaErnsta Grishin; TS: colotes DruceSubgenus Ernstacolotes ; new combination, was in SpialiaErnsta confusa ; new combination, was in SpialiaErnsta wrefordi ; new combination, was in SpialiaErnsta paula ; new combination, was in SpialiaErnsta secessus ; new combination, was in SpialiaErnsta dromus ; new combination, was in SpialiaErnsta ploetzi ; new combination, was in SpialiaTavetana Picard, 1949; TS: jeanneli Picard=Gomalia elma Gomalia jeanneli ; stat. rev., was a synonym of G. elmaGomaliaalbofasciata Moore, 1879; stat. rev., was a subspecies of G. elmaFavriacribrellum Muschampia Tutt, 1906; TS: proto OchsenheimerSubgenus Tuttia Warren, 1926; TS: tessellum H\u00fcbner=Muschampia tessellum Muschampia nomas Muschampia tersaEvans, 1949Muschampia nobilis Muschampia kuenlunus Muschampia protheon Muschampia gigas Muschampiaproto Ochsenheimer, 1808Muschampia proteides Muschampia mohammed Muschampia leuzeae Sloperia Tutt, 1906; stat. rev., was a synonym of Muschampia; TS: poggei LedererSubgenus Reverdinia Warren, 1926; TS: staudingeri Speyer=Muschampia proteus Muschampia prometheus Muschampia plurimacula Muschampia staudingeri Muschampia mustaEvans, 1949Muschampia lutulentus Muschampiapoggei Warrenohesperia Strand, 1928; stat. rev., was a synonym of Muschampia; TS: antonia SpeyerSubgenus Ramburia Warren, 1926 ; TS: antonia Speyer=\u2021Muschampiaantonia Reverdinus Ragusa, 1919; stat. rev., new placement, was a synonym of Carcharodus; TS: =\u2021altheae H\u00fcbner, [1800\u20131803] (floccifera Zeller)Subgenus Lavatheria Verity, 1940; new placement, was a synonym of Carcharodus; TS: lavatherae Esper=Muschampiafloccifera ; new combination, was in CarcharodusMuschampia orientalis ; new combination, was in CarcharodusMuschampia dravira ; new combination, was in CarcharodusMuschampia stauderi ; new combination, was in CarcharodusMuschampia baeticus ; new combination, was in CarcharodusMuschampia lavatherae ; new combination, was in CarcharodusSyrichtus Boisduval, [1834]; TS: alceae Esper=\u2020Spilolhyrus Duponchel, 1835; TS: alceae Esper=\u2020Carcharodusalceae Carcharodus tripolina The key provides phenotypic characters for all Carcharodina genera to aid their identification.1 and the pale spot in space CuA1-CuA2 positioned in the middle between the discal cell spot and the spot in cell M3-CuA1, or closer to the latter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Hindwing outer margin evenly rounded without crenulation. Fringes prominently checkered. Wings white-spotted : central pale spot in discal cell on dorsal forewing positioned before the origin of vein CuA1, and if not, then it overlaps with the CuA1-CuA2 cell spot, which is closer to the discal cell spot than to the spot in M3-CuA1 cell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Hindwing more or less crenulate or fringes uncheckered and hindwing slightly produced at vein 1A+2A. Wings marbled and with hyaline spots, if white-spotted, then central pale spot in discal cell on dorsal forewing usually centered around the origin of vein CuAAgyllia gen. n.Out of three spots in forewing discal cell, rectangular middle spot (the largest) closer to streak-like spot at distal end of cell than to well-developed and rounded basal spot. Male with costal fold. Uncus deeply incised. . . . . . . . . . . . . . . . . . . Out of three spots in forewing discal cell, rectangular middle spot (the largest) not closer to streak-like spot at distal end of cell than to basal spot, or basal spot absent. Male with or without costal fold. Uncus not deeply incised. . . . . . . . . . . . . . . . . . . . . 31 joins central spot to the outer (and not inner) spot in cell Sc+R1-RS. Hindwing submarginal pale spots in cells M1-M2 & M2-M3 offset basad from the rest of the submarginal spots in species with costal fold. Species without costal fold either lack basal white spots in discal cell on dorsal forewing , or on dorsal forewing in CuA2-1A+2A cell the outer lower median spot absent and inner lower median spot forming a bar with inner upper median spot, larger than the outer upper median spot. Gnathos dorsally joined to tegumen, if gnathos free, then coecum of aedeagus shortened or absent. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ernsta gen. n.Ventral hindwing with straight median white band not separated into sports, i.e., white spot in cell RS-M1-M2 & M2-M3 in line with other submarginal spots or absent. In species with straight entire median white ventral hindwing band (similar to Ernsta gen. n.), basal white spots in discal cell on dorsal forewing present and in CuA2-1A+2A cell inner upper median spot absent, outer upper median spot well developed, nearly the same size as inner lower median spot. Male without costal fold. Gnathos not joined to tegumen, aedeagus typically with coecum. . . . . . . SpialiaVentral hindwing median white band frequently broken into spots or if not, then usually directed basad at costa. Hindwing submarginal pale spots in cells MGomaliaFringes not checkered or indistinctly checkered. Hindwing outer margin wavy and slightly produced at vein 1A+2A. Mid-tibiae without a row of spines. Wings marbled and usually with hyaline spots. Caterpillar almost white, more elongated, foodplants Malvaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Fringes prominently checkered. Hindwing more or less crenulate. Caterpillar darker and stouter. . . . . . . . . . . . . . . . . . . . . . . 5Muschampia tessellum , differing by the subapical forewing white bar that almost always consists of 4 to 5 (instead of 3) spots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .FavriaMid-tibiae with a row of spines. Costa of valva with broad serrated process directed ventrad. Wings white-spotted. Single species currently included in this genus exhibits a nearly perfect, but apparently convergent, similarity in wing pattern with Mid-tibiae smooth, without a row of spines. Costa of valva without such process. Wings white-spotted or marbled and with hyaline spots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6MuschampiaAedeagus thin. Uncus not longer than tegumen. Wings white-spotted, if marbled, then valva longer than wide and forewing pale bar defining the end of discal cell and central hyaline spots well-developed. Caterpillar foodplants (where known) Lamiaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CarcharodusAedeagus very broad, expanded distally. Uncus longer than tegumen. Valva nearly as long as wide. Wings marbled and with hyaline spots, forewing pale bar defining the end of discal cell absent or inconspicuous and central hyaline spots smaller. Caterpillar foodplants Malvaceae and Euphorbiaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . We find the genomic perspective on the subtribe Carcharodina to be quite insightful. Complementary to morphological analysis, it confidently reveals new phylogenetic affinities and uniqueness of certain phylogenetic lineages. Many millions of base pairs in nuclear genome gene coding regions result in highly confident phylogenies and reveal well-supported monophyletic groups. We use these groups to refine the classification of Carcharodina and instead of 4 genera used previously, we utilize 7 (see the taxonomic list above). While our genera form very confident clades , other eAgylla to Ernsta, Favria to Gomalia, and Muschampia to Carcharodus. It is not clear that such treatment is better. First, Gomalia and Favria are phenotypically different, not giving immediate confidence in their unification. Second, branches in the tree that support each of the three pairs Ernsta + Agylla, Gomalia + Favria, and Carcharodus + Muschampia are shorter than the branches supporting each of these six genera individually. Thus, the combined genera are less prominent, and therefore are possibly less confident and less identifiable groups. Third, we will lose the name Muschampia, a genus traditionally used for decades.Pushing the cut back in time, we will lose, Carcharodus and Spialia (including Ernsta and Agylla). This would be a lumping treatment that nevertheless is appealing. Although the two genera are less prominent than our 7 , they are better defined than 4 and keep former Spialia intact. It is also possible to opt for an inconsistent treatment when some genera originated later than others, and a single cut through the tree does not define them. Future usage of these names and research will settle this question.Cutting the tree even further back in time results in just two genera: Grizzled and Marbled skippers of the Old Word are abundant and have been studied extensively over the years, likely better than many other groups of Hesperiidae. To our surprise, we found that genomic analysis gives a different perspective on their classification. We detect distinct phylogenetic lineages that we treat as new genera and we define subgenera. We correct phylogenetic placement of some species assigned to a genus they do not belong. We see that adding genomic analysis to the arsenal of taxonomists reveals findings that are not easy to obtain using morphological analysis.Supplementary file"} +{"text": "Scientific Reports 10.1038/s41598-021-04681-y, published online 18 January 2022Correction to: The original version of this Article contained an error in the order of the References 36 and 37. References 36 and 37 were published as References 37 and 36.The correct order of the references is listed below:PLoS ONE16, e0246317 (2021).36. Taylor, S. & Asmundson, G. J. Negative attitudes about facemasks during the COVID-19 pandemic: The dual importance of perceived ineffectiveness and psychological reactance. 37. Seres, G., Balleyer, A.H., Cerutti, N., Friedrichsen, J. & S\u00fcer, M. Face mask use and physical distancing before and after mandatory masking: No evidence on risk compensation in public waiting lines. 10.2139/ssrn.3924790 (2021).The original Article has been corrected."} +{"text": "Error in Figure/TableIn the original publication , two figAddition of an AuthorLaura-Jayne A. Ellis was not included as an author in the original publication. The corrected Author Contributions Statement appears here. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated.New Author Contribution statement:Author Contributions: Formal analysis, A.C.Q.; Methodology, A.C.Q., L.-J.A.E.; Supervision, I.L. and E.V.-J.; Writing\u2014original draft, A.C.Q.; Writing\u2014review & editing, I.L. and E.V.-J. All authors have read and agreed to the published version of the manuscript."} +{"text": "Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE).Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality.Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality.Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE . Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not . Conversely, having asthma strongly increased the risk on TE development . No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development.Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation. Furthermore, platelet hyperreactivity might also contribute to the development of TE, as increased baseline platelet activation markers, and increased platelet reactivity have been reported in these patients (COVID-19 (coronavirus disease 2019) is associated with pulmonary symptoms, including pneumonia or Acute Respiratory Distress Syndrome (ARDS) . This ispatients . Most ofAdenosine diphosphate (ADP) was from Sigma-Aldrich . Allophycocyanin (APC)-conjugated monoclonal Mouse Anti-Human P-selectin (CD62P) antibody clone AK4, Phycoerythrin (PE) conjugated monoclonal Mouse Anti-Human P-selectin antibody clone AK4, BD FACSCanto II, and FACSCanto II Diva software version 8.0.1 were from BD Biosciences . Fluorescein isothiocyanate (FITC) conjugated polyclonal Rabbit Anti-Human fibrinogen antibody (F011102-2) was from Dako .Formaldehyde (37%) was from Calbiochem . MgSO4 was from Merck . NaCl, KCl were from Sigma\u2013Aldrich . PAR (protease-activated receptor)-1 agonist SFLLRN (TRAP-6) was from Bachem . 1.2-mL polypropylene tubes were obtained from BRAND GmbH & Co. KG . 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) was from VWR International . Ninety-six-well PS flat-bottom plates were from Greiner Bio-one .Hospitalized patients (\u226518 years old) admitted to the University Medical Center Utrecht between March 17th and May 1st 2020 with a positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test, or with COVID-19 specific radiologic findings in case of uncertain RT-PCR status, were eligible for this retrospective study . Patient3). The median fluorescence intensity (MFI) of 5,000 gated platelets was determined (Platelet reactivity testing was performed by diluting 5 \u03bcL whole blood (collected into heparin tubes) 1:11 dilution in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered saline , containing either a concentration series of adenosine diphosphate ADP (0\u2013114 \u03bcM) or PAR1-activating peptide or TRAP-6 (0\u2013568 \u03bcM) and APC-conjugated or PE-conjugated Anti-Human P-selectin antibody clone AK4 to detect platelet P-selectin expression, and FITC-conjugated Anti-Human fibrinogen antibody to detect fibrinogen binding (reflects GPIIb/IIIa activation) for 30 min at room temperature. Platelet activation was stopped by fixing the sample for 20 min by 11-fold dilution into fixative (0.4% PFA in 0.9% NaCl). Samples were analyzed on a FACSCanto II using FACSDiva software version 8.0.1. Platelets were gated based on their forward and sideward scatter. We validated this gating strategy in a subset of our study cohort (12 patients) with a monoclonal antibody against the platelet-specific marker GP1b\u03b1. In this gate, 88.4% \u00b1 6.5% (mean \u00b1 SD) was positive , comorbidities , immunocompromising disease and/or medication, preexisting thromboprophylaxis , hospital thromboprophylaxis , therapeutic antithrombotic medication and on admission platelet count .Critical disease was defined according to the World Health Organization COVID-19 subgroup definitions as having clinical signs of severe pneumonia and meeting the ARDS criteria at any point during admission . TE diag2 test (n < 60) or Fisher's exact test (in case of less than five samples per cell). Statistical testing was performed in IBM SPSS statistics (version 25.0.0.2).Continuous variables are shown as median and interquartile range (IQR) and are compared using Mann-Whitney test. Categorical variables are shown as frequencies and percentages and are compared using ChiPlatelet reactivity stratified by clinical outcome was analyzed in PRISM GraphPad (version 8.3.0) by One-way ANOVA and Sidak's multiple comparisons test comparing the two groups at all concentrations of used platelet agonist.p- value < 0.05.Univariable and multivariable logistic regression models were made in IBM SPSS statistics to estimate the (adjusted) odds ratio of the clinical outcomes . Most of the variables that do not associate with clinical outcome in the univariable logistic regression model were excluded from analysis in the multivariable logistic regression model. Furthermore, a variable was excluded from multivariate logistic regression if the percentage of exposure was too low or too high in order to calculate the odds ratio. Four covariates were included in the multivariable logistic regression model to avoid overfitting in the model. For the clinical outcome TE covariates were age, asthma, any preexisting thromboprophylaxis and platelet reactivity in response to a maximum concentration of TRAP-6. For the clinical outcome all-cause mortality the covariates comprised age, hypertension, any preexisting thromboprophylaxis and baseline platelet reactivity. For all tests statistical significance was defined as a two-tailed We investigated whether increased platelet reactivity is a risk factor for thrombotic events or all-cause mortality in hospitalized COVID-19 patients. We enrolled 79 SARS-CoV-2 positive patients for this study and included 21 hospitalized SARS-CoV-2 negative patients (with a different diagnosis) as a control group . PlateleThe median age of these patients was 67 years (IQR: 54\u201375), more patients were male than female and hypertension (37%) was the most common comorbidity . The SARMost patients (85%) developed severe COVID-19 disease according to the World Health Organization guideline . Half ofp = < 0.001] and had a lower body mass index , with higher age and with higher platelet reactivity in response to TRAP-6 .Univariable logistic regression analysis revealed that the risk for developing TE was decreased in patients taking preexisting thromboprophylaxis . However, information on the development of TE in the control group was unavailable for this study. No difference in platelet reactivity was seen between the COVID-19 positive and negative control group of hospitalized patients based on P-selectin expression . By compSimilarly, we found that both baseline and triggered P-selectin expression by platelets were similar between survivors and non-survivors in this study and our We observed that platelet fibrinogen binding was decreased in COVID-19 patients compared to COVID-19 negative control patients, which suggested a decreased activation of GPIIb/IIIa . Similarin situ and is in line with findings from other studies (The incidence of TE 28%) and its predominant occurrence during ICU stay in this study is in line with other studies , 16. Onl studies , 8. Seve% and its studies . Two of p = 0.029; Indes et al. compared arterial thrombosis occurring in COVID-19 positive and negative patients and found that COVID-19 positive patients had higher D-dimer levels, were younger (64 vs. 70 years of age) and less often used preexisting antiplatelet medication compared to the negative control group (21 vs. 63%) , which can cleave and truncate the N-terminus of PAR-1 including the thrombin cleavage site, rendering PAR-1 unable to be activated by thrombin , 24. Botin vivo desensitization by thrombin. Patients taking any preexisting thromboprophylaxis prior to hospitalization had a 5-fold lower risk for TE development . This suggests that this might be beneficial for coping with COVID-19 associated hypercoagulability, and highlights the importance of therapy adherence in the general population.In conclusion, our study revealed that platelet reactivity in COVID-19 patients was lowered after TE development, possibly as a result of The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medisch Ethische Toetsingscommissie (METC) Utrecht. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.CC, AB, SSm, CS, SV, NP, SSe, AK, and AW designed and performed the experiments. BJ, JS, NJ, HG, RS, and SB gathered samples and clinical data. CC and BJ analyzed the data and wrote, with support from all other authors, the manuscript. SM, SN, MB, EV, LK, KK, and CM designed the study and supervised the project. All authors contributed to the article and approved the submitted version.-AMC: Dr. M. Coppens; Prof. Dr. N. P. Juffermans; Prof. Dr. S. Middeldorp-VUMC: Prof. Dr. C. M. P. M. Hertogh; J. G. Hugtenburg; Dr. E. J. NossentDrs. J. van den Akker; Dr. R. Bierings; Dr. H. Endeman; Dr. M. Goeijenbier; Prof. Dr. D. A. M. P. J. Gommers; Prof. Dr. M. P. G. Koopmans; Prof. Dr. T. Kuiken; T. Langerak, PhD candidate; Dr. M. N. Lauw; Prof. Dr. M. P. M. de Maat; D. Noack, PhD candidate; M. P. Raadsen, PhD candidate; Dr. B. Rockx; C. Rokx; K. Tong-Minh, PhD candidate; Dr. L van der Toorn; C. A. den UilTineke Roest, coordinating pharmacist.Dr. J. Manuel Soria, Unit of Genomics of Complex Diseases.M. L. Antoni; Dr. M. Bos; Drs. Burggraaf, PhD candidate; Prof. S. C. Cannegieter; Prof. Dr. H. C. J. Eikenboom; Dr. P. L. den Exter; Dr. J. J. M. Geelhoed; Prof. Dr. M. V. Huisman; Prof. E. de Jonge; Drs. F. H. J. Kaptein, PhD candidate; Dr. F. A. Klok; Dr. L. J. M. Kroft; Drs. L. Nab, PhD candidate; Dr. M. K. Ninaber; Prof. Dr. H. Putter; Dr. A. M. da Rocha Rondon; Dr. A. H. E. Roukens; Drs. M. A. M. Stals; PhD candidate; Prof. Dr. H. H. Versteeg; Dr. H. W. Vliegen; Dr. B. J. M. van Vlijmen.Dr. B. C. T. van Bussel; Prof. Dr. T. M. Hackeng; Drs. T. van de Berg; Prof. Dr. H. ten Cate; Dr. ir. Y. Henskens; Dr. H. Spronk; Prof. Dr. L. Schurgers; Drs. R. Bruggemann; Dr. B. Spaetgens; Dr. K. Winckers; Drs. R. Olie; Prof. Dr. M.A. Spruit.Dr. J. Leentjens; Dr. Q. de MastDr. M. van den Biggelaar; Prof. Dr. J. C. M. Meijers (Amsterdam Universitaire Medische Centra); Prof. Dr. J. Voorberg (Amsterdam Universitaire Medische Centra).Dr. B. de Laat.Dr. A. Ten Cate-Hoek.Prof. Dr. T. Lisman; Prof. Dr. K. Meijer.Prof. Dr. O. L. Cremer, Dr. G. Geersing, Prof Dr. H. A. H. Kaasjager, Dr. N. Kusadasi, Dr. A. Huisman, Dr. M. Nijkeuter, Prof. Dr. R. E. G. Schutgens, Dr. R. T. Urbanus, Dr. J. Westerink.B. Bindels; T. M. P. Nijdam; N. L. M. van de Ven; R. Verhaegh; B. W. Verboeket; D. Laane; K.van Wessem; F. Hietbrink; L. P. H. LeenenD. E. J. van Spengler; W. Buitenwerf; G. Giustarini; E. Mulder; H. Heijerman.A. D. Zabaleta; F. van den Bos; F. Stiphout.E. Rademaker; M. R. J. Varkila; N. de Mul; O. L. Cremer; A. Slooter.E. M. Delemarre; M. Limper; F. van Wijk; A. Pandit; H. Leavis; N. Vrisekoop.S. Haitjema; I. E. Hoefer.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In this review, the authors considered the promising species of vegetable crops for introduction andbreeding in the Russian Federation. An attempt was made to assess the possibilities of their breeding improvementfrom the standpoint of the presence of traits that limit large-scale production. Species that could potentially serveas sources of a high content of functional food ingredients (FFI) have been identified and characterized. For thesuccessful introgression of these species in the Russian Federation, we proposed the methodological approachesincluding the assessment of the potential cold resistance of thermophilic crops in the mature male gametophytein vitro . The increase in the biodiversity of vegetable plants and improving of their nutritional value should be recognized as one of the main tasks, along with the growth of crop productivity. It is proposedto use the ratio of the total number of the registered cultivars of a particular crop to the number of years since thefirst cultivar of that crop has been included in the State Register of Breeding Achievements Admitted for Use as ameasure of demand. It is advisable to formalize the trait \u201chigh content of FFI\u201d in crops, taking as a basis, for example,a 2\u20134-fold excess of the content of any FFI or their complex in a cultivar over the crop\u2019s standard (reference) value.Such varieties should be included in the State Register of Breeding Achievements Approved for Use as a separatelist. The purpose of their separation in the State Register is to ensure the potential interest of investors and businessstructures in the sale of functional food on the market. The paper discusses in detail the most promising species ofintroduced vegetable crops from five families . The following species are proposed as potential sources of high FPI content: Brassica oleracea ssp. oleracea,B. oleraceae var. alboglabra, B. rapa ssp. chinensis, B. rapa ssp. narinosa, B. rapa ssp. nipposinica, B. rapa ssp. rapa,B. juncea, Cochlearia officinalis, Lepidium sativum, Amaranthus caudatus, A. cruentus, A. hypochondriacus, A. dubius,A. tricolor, A. lividus, species in the genus Physalis L., Momordica charantia, Benincasa hispida, Cucumis metuliferus,Vigna unguiculata The domestication of many cultivated plants, including vegetable crops, often took place around the world in the form ofintroduction . Some new species beganto occupy leading positions in peasant farms, displacing theprevious \u201cfavorites\u201d, while others remained unclaimed. Theyare called \u201cnon-traditional crops\u201d in the scientific agriculturalliterature.The lack of planting material, insufficient awareness ofthe population about nutritional andmedicinal value of non-traditional crops and the lack of information about specific cultivation technology of these cropsare considered to be possible reasons for insufficient use ofnon-traditional crops . In addition to thesethree reasons, another important factor in Russia is the presence of agrobiological traits and/or their expression, whichlimits the possibility of effective cultivation of such cropsin the conditions of real agrocenosis in many regions of thecountry. A long growing season exceeding the duration of thefrost-free period of many territories of the Russian Federation,poor resistance to low temperatures, high sensitivity of thegenerative sphere to environmental factors, susceptibility todiseases and pests, inadequacy of the quality of marketableproducts to consumer expectations also limit the potentialof new crops and the possibility of their positioning as foodproducts, including functional onesThe All-Union Institute of Plant Industry (now the All-Russian Institute of Plant Genetic Resources (VIR)), headed byN.I. Vavilov, played an outstanding role in the collecting andstudying of the collection of vegetable plants which werenew for Russia. Alot of new species were first included in thecollection of the Institute with Vavilov\u2019s active participation.At present time the world collection of vegetable and meloncrops of the Russian Federation, stored in the VIR, has morethan 50 thousand samples belonging to 29 families, 145 genera, and 610 species. The status of the collection samplesis as follows: 5.5 % are wild species and primitive forms;34 % are landraces; 49 % \u2013 breeding varieties; 11.5 % \u2013 different types of breeding lines and hybrids, including hybrid populations. The uniqueness of the collections ofsome vegetable crops reaches 80 %.Vegetable crops presentedin the VIR collection belong mainly to 9 families:Brassicaceae Burn.;Solanaceae Juss.;Leguminosae Juss.;Cucurbitaceae Juss.;Alliaceae Borkh.;Apiaceae Lindl.;Amaranthaceae Juss.;Asteraceae Bercht. et J. Presl;\u2012 Lamiaceae Martinov.1. Such species require significant breeding and genetic improvement forcultivation in a real agrocenosisThe diversity of these large taxonomic groups is exceptionally great in terms of the biochemical characteristics ofthe representatives of these families. Some of the speciesand crops that deserve priority inclusion in the introductionprograms from the standpoint of their biochemical valueand the possibility of use as functional foods (FF) are listedbelow. At the same time, the problem of expanding production of cold-resistant crops used as leafy vegetables inagricultural enterprises is largely associated with the lack ofagricultural technologies and the availability (supply) of highquality seed material and, to a lesser extent, with their adaptivepotential , compared with traditional heat-lovingvegetable crops. On the contrary, many introduced speciesof heat-loving vegetable plants from the Solanaceae, Cucurbitaceae, and Leguminosae families with narrow ecologicalplasticity are carriers of traits that prevent the scaling uptheir production in the regions of Russia http://vavilov.elpub.ru/jour/manager/files/Suppl_Fotev_Engl.pdfSupplementary Material is available in the online version of the paper: The Table provides basic information about the range ofnon-traditional vegetable crops presented in the State Register.The number of registered cultivars varies from 1 to 61 (Chinese cabbage), while the period of stay in it from the year of registration of the first cultivarup to01.01.2021 varies from 12 to 78 years (leaf mustard). Most of the cultivars have beenrelatively recently bred and included in the State Register: themedian of the year of inclusion falls on 2006\u20132020. The largestminus values of the coefficient of asymmetry by a year: \u20132.8,\u20132.4, \u20132, respectively, for mustard, Chinese cabbage, and bittermelon, illustrate a sharper increase in the number of inclusionsin the State Register in recent years (which means an interestfor them from consumers and breeders), compared with an earlier period \u2013 the year of registration of the first cultivar. On the contrary, the interestof breeders in the registration of amaranth cultivars has decreased in comparison with theprevious period \u2013 the coefficient of skewness is 1.1. Leptokurtic (peaked) distribution byyears of inclusion in the State Register cultivars of Chinese cabbage, mustard, and bittermelon with kurtosis indices, respectively, 10.3, 9.9, and 4.0 shows a significant increasein the number of registrations of breeding achievements for these species around themedian indicator (year). The ratio of the total number of registered cultivars by crop tothe number of years since the year of inclusion in the State Register of the first cultivarshows the relative degree of demand for the crop, although this may also indicate thelack of available intraspecific genetic diversity (biodiversity) necessary for its breedingimprovement. The calculated \u201ccoefficient of demand for the crop\u201d turned out to be themaximum for asparagus vigna (179), Chinese cabbage (107), and pakchoi (95).Below, as an example of the choice of the object of introduction and selection, wewill consider information about the three most promising, from our point of view, crops.Asparagus vigna (Vigna unguiculata (L.) Walp.) is a valuable vegetable crop that couldbe used as a functional food . Its cultivation in Russia is limited due tohigh heat demand, negative reaction of many cultivars for a long day, and susceptibility tosome pathogens. The collection of cowpea VIR includes 4092 specimens of 9 species ofthe genus Vigna Savi . As of 01.01.2021, 25 Russian cultivarsof V. unguiculata are included in the State Register.Cold hardiness is a complex trait in many crops. There are different methods of evaluating cold resistance. For example, a close positive correlation was found between theresistance to low temperatures of microgametophyte and sporophyte in tomato cultivars. According to V.V. Vinogradova (1988) \u201cwhen adapting tomato to low temperatures, the most effective assessment of cold resistance is themethod of pollen germination in the solution of 15 % sucrose and H3BO3 (100 mg/l) at6\u201310 \u00b0C\u201d (p. 78). On a solution of a synthetic osmotically active substance \u2013 polyethylene glycol with a molecular weight of 6000 (PEG 6000), which does not participate inthe metabolism of plant cells , species, varieties, and interspecifichybrid forms of tomato combining resistance to low and high temperatures for stagesof pollen germination in vitro were selected . To assess the resistance ofdifferent samples of cowpea to low temperatures, it is advisable to evaluate the growthresponse of pollen in vitro also on a PEG 6000 solution at a concentration of 20 % withboric acid 0.006 % . In the Central Siberian Botanical Garden(hereinafter CSBG), the highest indices of cold resistance in the form of the ratio ofpollen germination at low (10 \u00b0C \u2013 24 h) temperature to the same index at 25 \u00b0C for 3 hwere observed in V. unguiculata samples: Lulin (87 %), Zinder (65 %) and Sibirskiyrazmer (46 %) .In addition, the cultivars of asparagus cowpea, Sibirskiy razmer , and Yunnanskaya, bred in Russia have a neutral reaction to day length.Selected forms that showed a high level of resistance to Botrytis cinerea Pers. andSclerotinia sclerotiorum (Lib.) de Barywere selected in the CSBG: forma 901, formaNo. 323 [striped], Early Prolificacy Xiao Bao #2, F1 (Early Prolificacy Xiao Bao #2\u00d7Sibirskiy razmer) and F3 (Early Prolificacy Xiao Bao #2\u00d7Sibirskiy razmer) .Wax gourd (Benincasa hispida (Thunb.) Cogn.) originates from Indochina and iswidely cultivated in India, Japan, China, and many other tropical countries. Wild waxgourds have small fruits (<10 cm in length), while most cultivars produce giant fruits(up to 80 cm in length and weighing over 20 kg).Wax gourd fruits contain vitamins, flavonoids, triterpenoids, and metabolites that canbe used in the treatment of various diseases. The plant is used as a tonic for the brain,heart disease, and nosebleeds . This crop can be seen as avaluable FF.The first cultivar in Russia of wax gourd \u2013 Akulina was created in the CSBG.The direction for the improvement of the crop can be the breeding of more cold-resistantcultivars, gynoecious forms, and F1 hybrids based on them.Kiwano (Cucumis metuliferus E. Mey. ex Naudin) is a vegetable crop, the fruits ofwhich can be stored for up to six months under normal (\u201croom\u201d) conditions. Only onecultivar \u2013 Zeleniy drakon (Green Dragon) \u2013 included in the State Register is bredin the CSBG and characterized by a short period from germination to fruiting and highproductivity in the outdoor conditions in the south of Western Siberia and greenhouses.Kiwano alkaloids have a protective effect on both theliver and kidney tissue and antiviralproperties against Newcastle disease caused by a virus fromthe family Paramyxoviridae, a dangerous pathogen for birds.Kiwano fruit tastes good but contains a lot of seeds. The useof parthenocarpy can solve this problem. It is known that ashort day and low temperatures results in the formation of parthenocarpic fruits in this crop.In addition, kiwano plants can serve as good rootstocksfor watermelon against rootworm nematode from the genusMelodogyne Goeldi and for melon(Cucumis melo), due to resistance to nematodes and fusarium.As discussed above, the species and forms of vegetable cropsthat are promising for the Russian Federation were consideredfor introduction and subsequent breeding. Particular attentionis paid to the species \u2013 potential sources of high functionalfood ingredients (FFI) content. These primarily include species of the Brassicaceae family: B. oleracea ssp. oleracea,B. oleraceae var. alboglabra, B. rapa ssp. chinensis, B. rapassp. narinosa, B. rapa ssp. nipposinica, B. rapa ssp. rapa,B. juncea, Cochlearia officinalis ssp. arctica, Lepidiumsativum; Amaranthaceae: A. caudatus, A. cruentus, A. hypochondriacus, A. dubius, A. tricolor, A. lividus; Solanaceae:species Physalis L.; Cucurbitaceae: Momordica charantia,Benincasa hispida, Cucumis metuliferus; Leguminosae: Vigna unguiculata. The biological characteristics of introducedspecies limiting the scale of production of specific introducedcrops in Russia are indicated. It is proposed the methodological approach for evaluation of resistance to low temperatureswith the use of its assessment in the phase of a mature malegametophyte of Vigna unguiculata in vitro as an example.The trait \u201chigh content of FFI\u201d in a crop must be specifiedtaking a 2\u20134 times excess of the content of individual FFI ortheir complex in the cultivar transferred to the State varietytesting over the crop standard (reference) values as a basis.Such cultivars should be included in the State Register ofSelection Achievements Authorized for Use in a separate list.The purpose of such allocation is to ensure the future interestof producers, investors, and business structures in the sale ofFF vegetable products on the poor market of vegetables ofthe Russian Federation.To increase the efficiency of introduction and breeding, itis proposed to use the index of the ratio of the total number ofregistered cultivars by a crop to the number of years since theyear of inclusion to the State Register of the first cultivar as acharacteristic of the degree of demand for the crop.The authors declare no conflict of interest.Abbas Z.K., Saggu S., Sakeran M.I., Zidan N., Rehman H., Ansari A.A.Phytochemical, antioxidant and mineral composition of hydroalcoholic extract of chicory (Cichorium intybus L.) leaves. 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DOI 10.5897/AJB2017.16374.Salvador M.J., Andreazza N.L., Pascoal C.R.F., Pereira P.S., Fran\u00e7a S.C., Zucchi O.L., Dias D.A. Bioactive chemical constituents andbiotechnological production of secondary metabolites in Amaranthaceae plants, Gomphreneae tribe. In: Biotechnological Productionof Plant Secondary Metabolites. 2012;124-158. DOI 10.2174/978160805114411201010124.Sokolova D., Shelenga T., Zvereva O., Solovieva A. Comparative characteristics of the amino acid composition in amaranth accessionsfrom the VIR Collection. Turk. J. Agric. For. 2021;45(1):68-78.Solovieva A.E., Artemieva A.M., Sh\u00fctze V. Features of the accumulation of glucosinolates in the Brassicaceae family. Doklady Rossiyskoy Akademii Selskokhozyaystvennykh Nauk = Proceedings ofthe Russian Academy of Agricultural Sciences. 2013;169:12-14. (inRussian)Steuter A.A., Mozafar A., Goodin J.R. Water potential of aqueouspolyethylene glycol. Plant Physiol. 1981;67:64-67. DOI 10.1104/pp.67.1.64.Vavilov N.I. Five Continents. Moscow: Mysl Publ., 1987;19-171. (inRussian)Vinogradova V.V. Assessment of cold resistance in vegetable andpumpkin crops. In: Diagnostics of Plant Resistance to Stress Conditions. Leningrad: VIR Publ., 1988;75-84. (in Russian)Vishnyakova M.A., Aleksandrova T.G., Buravtseva T.V., Burlyaeva M.O., Egorova G.P., Semenova E.V., Seferova I.V., Suvorova G.N. Species diversity of the VIR collection of grain legumegenetic resources and its use in domestic breeding. Trudy po Prikladnoy Botanike, Genetike i Selektsii = Proceedings on Applied Botany, Genetics, and Breeding. 2019;180(2):109-123. DOI 10.30901/2227-8834-2019-2-109-123. (in Russian)Yamasaki J., Takahata K., Kim O.-K., Negishi H., Arie T., Morita Y.,Shinohara H. Control of bacterial wilt caused by Ralstonia solanacearum and Fusarium wilt by Fusarium oxysporum f. sp. lycopersici by using pepino (Solanum muricatum Aiton) as a rootstockof tomato. J. Agr. Sci. Tokyo Univ. Agr. 2020;65(3):76-82. https://ci.nii.ac.jp/naid/120006949478/en/. (in Jap.)"} +{"text": "Melitaeaala Staudinger, 1881 complex are distributed in Central Asia. Here we show that this complex is a monophyletic group including the species, M.ala, M.kotshubeji Sheljuzhko, 1929 and M.enarea Fruhstorfer, 1917. The haploid chromosome number n=29 is found in M.ala and M.kotshubeji and is, most likely, a symplesiomorphy of the M.ala complex. We show that M.ala consists of four subspecies: M.alazaisana Lukhtanov, 1999 , M.alaala (Dzhungarian Alatau), M.alabicolor Seitz, 1908 and M.aladeterminata Bryk, 1940 . We demonstrate that M.kotshubejikotshubeji (Peter the Great Mts in Tajikistan) and M.kotshubejibundeli Kolesnichenko, 1999 (Alai Mts in Tajikistan and Kyrgyzstan) are distinct taxa despite their geographic proximity in East Tajikistan. Melitaeaenarea is widely distributed in the southern part of Central Asia and is sympatric with M.kotshubeji.The species of the Melitaea Fabricius, 1807. The combination of molecular and cytogenetic methods is a useful tool for taxonomic studies and M.par, 1849 species Melitaeaala Staudinger, 1881, M.kotshubeji Sheljuzhko, 1929, M.ninae Sheljuzhko, 1935, M.chitralensis Moore, 1901, and M.enarea Fruhstorfer, 1917. According to van M.acraeina Staudinger, 1881, M.ninae Sheljuzhko, 1935, Melitaeaala Staudinger, 1881, M.didymina Staudinger, 1895, M.chitralensis Moore, 1901, M.enarea Fruhstorfer, 1917, M.bundeli Kolesnichenko, 1999, M.kotshubeji Sheljuzhko, 1929, M.sutschana Staudinger, 1881 and M.yagakuana Matsumura, 1927 .The species of this complex are distributed in Central Asia . AccordiM.ala and M.enarea are sister species, and M.acraeina is a phylogenetically distant species which is a sister to the lineage . Melitaeasutschana was found as a member of the M.didyma species complex which is a sister to the lineage ) ) . In our M.kotshubejikotshubeji were studied as previously described (MI) and metaphase II (MII) were examined using an original two-phase method of chromosome analysis were studied as previously described . Legs were used as a source for DNA isolationStandard escribed . COI seqM.kotshubejibundeli Kolesnichenko, 1999) were processed in the Department of Karyosystematics of Zoological Institute of the Russian Academy of Sciences using primers and protocols described by Legs from 6 specimens using their standard high-throughput protocol described by McGuire Center for Lepidoptera and Biodiversity (MGCL), Florida Museum of Natural History, University of Florida, Gainesville, Florida, USA. Photographs of these specimens, as well as collecting data are available in the of Life Data System (BOLD), projects Butterflies of Palearctic (BPAL) and Butterflies of Palearctic Part B (BPALB) at http://www.boldsystems.org/.Legs from 28 specimens of COI sequences for DNA barcode analysis > 200] using the program Tracer v1.7.1 (http://tree.bio.ed.ac.uk/software/figtree/).Sequences were aligned using the BioEdit software and editr v1.7.1 . The firMI and MII cells of four studied individuals of M.kotshubejikotshubeji also formed a clade, but its support was relatively low formed the well-supported M.didyma species group , relatively weakly differentiated subclades were found. These are (1) M.alaala, (2) M.alairtyshica, (3) M.alazaisana, (4) M.alabicolor (clade b1) and (5) M.alabicolor (clade b2). We also calculated the uncorrected COI p-distances within has relatively low interspecific chromosome number variation. The representatives of basal clades , M.diamina , M.athalia , M.trivia and M.phoebe species groups demonstrate n=30\u201331 is karyotyped (n=29). In the Melitaeapersea species complex, n=27 is found in two species. In the Melitaeaala species complex, n=29 is found in two species studied.The Melitaea . This grMelitaea . MelitaeM.didyma group. Thus, for the species of the M.ala complex n=29 is a symplesiomorphy.Based on the distribution of the known chromosome numbers Table relativeM.ala have relatively high support .An especially low level of differentiation (0.3\u20130.5%) was found between the clades b1 and b2 clades was found between the des Fig. . However\u20130.8% wasM.alaala, M.alabicolor and M.alazaisana.Thus, within the studied populations, three subspecies can be distinguished. These are Melitaeaalaala is distributed in the Dzhungarian Alatau in East Kazakhstan Fig. is interov, 1999 and was nn, 1847 . DNA barCurrently, there is a tendency to consider as a species any group of populations with a minimum set of fixed differences. We are almost certain that, given this trend, the subspecies discussed above will be interpreted by some authors as species in the future. Nevertheless, in our opinion, in accordance with the subspecies criteria that should be assigned to M.ala. The types of these taxa were studied by the first author of this article in 2007 during a visit to Swedish Museum of Natural History.M.didymaallah Bryk, 1940 has the wing pattern with clear characters of M.alaala described by ide Fig. . Most liMelitaeaninae , M.enarea and M.mixta Evans, 1912 .The specimens identified as ikistan) and M.cC158427) were rep"} +{"text": "Proc. Natl. Acad. Sci. U. S. A. 108, 14306\u201314311.\u201dIn the original article, the reference for Maywood et al. (2011) was incorrectly written as \u201cMaywood, E. S., Chesham, J. E., Meng, Q. J., Nolan, P. M., Loudon, A. S. I., and Hastings, M. H. (2011). Tuning the period of the mammalian circadian clock: additive and independent effects of CK1 epsilon(Tau) and Fbxl3(Afh) mutations on mouse circadian behavior and molecular pacemaking. J. Neurosci. 31, 1539\u20131544.\u201d It should be \u201cMaywood, E. S., Chesham, J. E., O'Brien, J. A., and Hastings, M. H. (2011). A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Dear Editor,brightCD16\u2212 natural killer (NK), putative pro\u2010metastatic cells,brightCD16\u2212 NK cells.We investigated the clinical outcome of treating castration\u2010resistant prostate cancer (CRPC) patients with autologous immunohybridoma cell (aHyC) vaccine generated by electrofusing autologous dendritic (DC) and tumor cells (TC), and tested whether the immunological response, involving the CD56Despite advances in cancer immunotherapy, the only approved CRPC immunotherapy to date is a cell\u2010based vaccine (sipuleucel\u2010T),Here, whole TCs were electrofused with DCs to produce aHyC vaccine.Twenty\u2010two men with CRPC were included Table ; 19 of tThe treatment with aHyC revealed only a few and mild (grade 1) intervention\u2010related adverse events . Different modes of functioning, all scoring above 80 value was higher in the aHyC group than in the placebo\u2010first group of [+ T cells increased in both groups. However, an increase in regulatory CD25++CD127low, activated helper CD4+CD69+, and cytotoxic T cells (CD8+) and a decrease in total NK cells compared to baseline were recorded only in aHyC\u2010first group and was determined from the first application of aHyC to the cutoff date or the patient's death (any cause). The median OS was 58.5 months suggests that a relatively high increase in peripheral CD56brightCD16\u2212 NK cells shortens survival. Similarly, a negative correlation between the abundance of CD56brightCD16\u2212 NK cells and OS in melanoma patients was observed.Negative correlation between the survival time and change in the CD56brightCD16\u2212 NK cell subpopulation in peripheral blood, benefiting CRPC patient survival.In conclusion, these results indicate that aHyC treatment attenuates an increase in CD56This study was conducted in accordance with the provisions of the Declaration of Helsinki and was approved in June 2013 by the National Medical Ethics Committee and the Agency for Medicinal Products and Medical Devices of the Republic of Slovenia, part of European Medical Agency (EMA). Trial EMA registration: EUDRACT: 2012\u2010005498\u201029. All participants signed written informed consent prior to inclusion in the study.The authors declare no conflict of interest.This work was supported by grants P3 310, J3 6790, J3 6789, and J3 9266 from the Slovenian Research Agency, by CipKeBip, COST Action BM1002, EU COST Action CM1207\u2010GLISTEN, and EU COST Action CA 15214 EuroCellNet. The funding sources had no involvement in study design, collection, analysis and interpretation of data, the writing of the report, and the decision to submit the article for publication.H.H.C., S.H., M. Gabrijel, M.K., A.I., M.J., and R.Z. conceptualized the study. H.H.C., M. Gabrijel, S.T.B., M.C., and M.J. contributed in methodology. H.H.C., M. Gabrijel, and S.T.B. helped in validation. H.H.C., M.K., and N.K. helped in formal analysis. H.H.C., S.H., M. Gabrijel, S.T.B., A.N.K., L.L., and M. Grmek investigated the study. H.H.C., S.H., A.N.K., L.L., and M. Grmek contributed in data curation. H.H.C. and S.H. wrote the original draft. All the authors reviewed and edited the manuscript. H.H.C. and R.Z. directed the study. H.H.C., S.H., M. Gabrijel, A.I., A.K., and R.Z. supervised the project. S.H., G.L., A.I., and A.K. provided resources. S.H., A.I., and R.Z. acquired funding. N.K. provided software.Data generated and analyzed during the current study are available from the corresponding author on reasonable request. Clinical trial protocol is available at link: lnmcp.mf.uni\u2010lj.si/Protocol.pdf. Contact Matja\u017e Jeras for the immunology part.Supporting InformationClick here for additional data file."} +{"text": "The Siberian wood frog Rana amurensis Boulenger, 1886 is the most hypoxia-tolerant amphibian. It can survive for several months in an almost complete absence of oxygen. Little is known about the mechanisms of this remarkable resilience, in part because studies of amphibian genomes are impeded by their large size. To make the Siberian wood frog more amenable for genetic analysis, we performed transcriptome sequencing and de novo assembly for the R. amurensis brain under hypoxia and normoxia, as well as for the normoxic heart. In order to build a de novo transcriptome assembly of R. amurensis, we utilized 125-bp paired-end reads obtained from the brain under normoxia and hypoxia conditions, and from the heart under normoxia. In the transcriptome assembled from about 100,000,000 reads, 81.5 % of transcripts were annotated as complete, 5.3 % as fragmented, and 13.2 % as missing. We detected 59,078 known transcripts that clustered into 22,251 genes; 11,482 of them were assigned to specific GO categories. Among them, we found 6696 genes involved in protein binding, 3531 genes involved in catalytic activity, and 576 genes associated with transporter activity. A search for genes encoding receptors of the most important neurotransmitters, which may participate in the response to hypoxia, resulted in a set of expressed receptors of dopamine, serotonin, GABA, glutamate, acetylcholine, and norepinephrine. Unexpectedly, no transcripts for histamine receptors were found. The data obtained in this study create a valuable resource for studying the mechanisms of hypoxia tolerance in the Siberian wood frog, as well as for amphibian studies in general. Next-generation sequencing revolutionized the studies in thefield of molecular genetics. In contrast to early whole-genomeprojects, this technology presents a quick and relatively cheapway to obtain genome-wide information for non-model organisms.However, for organisms with large genome sizes, suchas amphibians, this is still a challenge due to many repeatsequences, frequent cases of polyploidy and high costs associatedwith the sequences of large genomes . Among the family Ranidae, there are currently onlythree genome assemblies: Rana temporaria, Glandirana rugosa,and Lithobates catesbeianus . Available transcriptomesare more numerous; however, they are still providedonly for a limited number of members of the family Ranidaeand do not always meet the high-quality standards of moderntranscriptome assemblies.Assembled transcriptomes would be useful resources forstudies on the emergent model species. Among these speciesare the northern amphibians that adapted to extreme conditionsof the northern Palearctic. These include highly freeze-tolerantRana sylvatica LeConte, 1825 , R. arvalis Nilsson,1842 , Hyla japonica G\u00fcnther,1859 , and the urodelas Salamandrellakeyserlingii Dybowski, 1870 and S. schrenkii , as well as the hypoxiatolerantSiberian wood frog Rana amurensis Boulenger, 1886. These species are intensely studiedbecause they represent one of the most remarkable adaptationsof vertebrates to extreme conditions and could giveinsights into ischemia treatment and organ transplantation.Earlier studies of freeze- and hypoxia tolerant amphibianswere mostly aimed at their physiology and biochemistry, butstudying genetic systems becomes more important .Amphibians in general are believed to be not particularlytolerant to hypoxia: adults of the different studied species cansurvive for a few hours to a few days even at low (near-zero)temperatures in water with low oxygen content . However, the Siberian wood frog R. amurensisBoulenger, 1886 is unique among amphibians in its abilityto survive almost complete anoxia for several months . This makes it a promising model object forstudying hypoxia tolerance. Metabolomic patterns in its organsindicate dramatic changes in biochemical pathways underhypoxia . However, these patternsare not easy to interpret, and this could be facilitated by theanalysis of gene expression and gene networks. In order tocreate a resource for studying gene expression in the Siberian wood frog, we performed sequencing, de novo assembly, andannotation of the transcriptome of this species.Brain and heart are the most sensitive to hypoxia , so we used transcripts from theseorgans for transcriptome construction. To test the assembledtranscriptome, we also performed a search for neurotransmitterreceptor genes: it was demonstrated that neurotransmitters mediate hypoxia response inturtles, so we hypothesized that this might also be true forthe Siberian wood frog.RNA extraction and sequencing. Specimens of the Siberianwood frog were collected in September 2019 near theLesopilnoye village, Khabarovsk Krai . Wefollowed approved methods under appropriate permits issuedby cognizant governmental agencies (No. 001/04-19).Frog handling, hypoxia exposure, and organ extraction wereperformed as described in S.V. Shekhovtsov et al. (2020):briefly, the frogs were distributed by 5\u20137 individuals into 10 Lcontainers filled with water (oxygen level 7\u20138 mg/L) and acclimatedto low temperatures: 2 days at 14\u201315 \u00b0C, for 4 daysat 8, 4, and 2\u20133 \u00b0C. Acclimation was performed in a TSO-1/80SPU thermostat and in a WT-64/75 climatictest chamber .Control animals were kept in open containers; those exposedto hypoxia, in closed airtight bottles. The dissolved oxygencontent was measured daily by a HACH HQ30D Flexi digitalsingle-channel device with a luminescent LDO101 sensoruntil it reached 0.2 mg/L. After 17 days in hypoxia, animalswere slaughtered as quickly as possible, and the organs wereextracted and immediately submerged in liquid nitrogen. RNAwas extracted using commercial kits followingthe manufacturer\u2019s protocolThe purity of total RNA was estimated on a NanoPhotometer. The quantity of total RNA wasmeasured by fluorimeter Qubit 4.0 . The quality of total RNA was evaluated using aBioanalyzer 2100 . Then, from800\u20131000 ng of pure and good quality total RNA (RIN \u2265 7),polyA mRNA was isolated using NEBNext Poly(A) mRNAMagnetic Isolation Module .cDNA libraries were prepared using NEBNext Ultra IIDirectional RNA Library Prep Kit for Illumina (New EnglandBiolabs) according to the manufacturer\u2019s protocol. Theconcentration of amplified libraries was estimated by fluorimeterQubit 3.0 (ThermoFisher Scientific). Size selectionof pooled libraries was performed on the BluePippin system using 1.5 % agarose gel cassettes with 300\u2013400 bp target size. The quality of libraries was verifiedon a Bioanalyzer 2100 (Agilent Technologies) using DNAHigh Sensitivity Kit. Range of library fragment size was200\u20131000 bp. The concentration of libraries was validatedby qPCR using 2.5\u00d7 EVA Green Mix andprimers for Illumina adapters . Librarieswere then sequenced on a HiSeq 2500 withpaired-end 125 bp readsTranscriptome assembly. RNA reads from R. amurensisbrain and heart samples were used for de novotranscriptome assembly. The quality of raw reads was estimatedwith FastQC (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/). Adaptor trimming and read filteringwere performed using fastp with defaultparameters. The rCorrector tool wasused for correcting the non-solid k-mers within reads andremoving unfixable ones. Transcriptome assembly was performedon all samples via Trinity with --SS_lib_type FR parameter for a stranded library. Thebasic assembly metrics were calculated using the \u2018TrinityStats.pl\u2019 script incorporated in Trinity. Redundant transcriptswere identified and removed from the assembly viaCD-HIT with the following parameters:-c 0.98 -p 1 -d 0 -b 3 -T 5 -M 2000. Completeness of the assembledtranscriptome was estimated using BUSCO with the mode -m transcriptome and lineage\u201ctetrapoda_odb10\u201d parameters.Transcript quantification. The transcript abundance wasestimated using the \u2018align_and_estimate_abundance.pl\u2019 script included in Trinity. Both gene- andisoform-level abundance matrices for all samples were constructedwith the \u2018abundance_estimates_to_matrix.pl\u2019 script.The comparison of samples based on their expression leveland the subsequent visualization procedures were performedusing the \u2018PtR\u2019 script as well as custom scripts.Assembly annotation and candidate coding regionsidentification. We used a collection of scripts from TransDecoder to identify the candidate codingregions. First, open reading frames (ORF) were retrievedfrom the assembly file. A set of the longest obtained ORFswere then queried against Swiss-Prot and Pfam databases to search for sequence similarity withknown proteins and Pfam protein domains. To achieve bettercomputational efficiency, we used hmmsearch v3.3.2 scripts instead of hmmscan for domain identification,and the homology search was done with Blast+ . The output generated from the database searchingstep was then used for the prediction of coding regions usingthe TransDecoder.Predict script from TransDecoder and fortranscriptome assembly annotation via the Trinotate pipelineGene Ontology (GO) analysis. The Trinotate report obtainedin the assembly annotation step was used to characterizethe annotated genes according to their biological role andthe occupied cell compartments. We counted the number ofannotated genes per GO category for the cellular component(CC), biological process (BP), and molecular function (MF)sub-ontologies at level 2. Graphical representation was done using an in-house R script. Annotated genes without assignedGO categories were classified according to the PFAM proteinfamilies they associated with.Searching for neurotransmitter receptors. We extracted aset of genes encoding receptors of the main neurotransmitters from the Xenopus genome database. Xenbase was chosen overmore closely related species due to its longer history and betterannotation. For each annotated gene, the transcripts weretaken for Xenopus tropicalis, or, if absent, for X. laevis. Weperformed a blastn search for this Xenopus transcript datasetin the assembled transcriptome (Trinity_filtered.fasta) withe-value <1e\u20135. Transcripts with > 70 % sequence similaritywere included in the final dataset.De novo transcriptome assemblyIn order to build a de novo transcriptome assembly of R. amurensis,we utilized 125 bp paired-end reads obtained fromthe brain under normoxia and hypoxia conditions and from the heart undernormoxia (RAHN sample).After filtering out low-quality reads, a total of 98,948,825reads from all three samples were used for the subsequent transcriptomeassembling procedure. An initial assembly consistedof 610,890 Trinity \u2018genes\u2019 composed of 839,939 transcriptswith an average contig length of 639 bp (or 481 bp based onthe longest isoform per Trinity \u2019gene\u2019). In addition, we filteredout 56,044 redundant transcripts using CD-HIT. Once filteringwas done, the final assembly was generated (Table 1).Estimates using BUSCO demonstrated that 81.5 % of thetranscripts were annotated as complete, 5.3 % as fragmented,and 13.2 % as missing.Abundance quantificationFor each RNA sample, we calculated the levels of transcriptabundances using the resulting assembled transcriptome. TheSalmon alignment rate varied from 87.9 to 91 % across allsamples, which is an additional indicator of good quality of thefinal assembly. The majority of Trinity \u2018genes\u2019 turned out tobe low-expressed, and only 20,251 out of 588,475 \u2018genes\u2019 hadexpression levels \u2265 10 TPM (transcripts per million) in at leastone sample. The sum of gene expression counts per sample varied from 28,587,718 to 31,477,299 with the largest valuefor the R. amurensis brain sample under hypoxia .Moreover, we observed tissue-specific differences in gene expressionlevels between brain and heart samples .As was expected, we found that the brain transcriptomes correlatedbetter with each other (Pearson\u2019s r = 0.770) than with theheart transcriptome . In addition,we counted the number of genes with more than 2-foldexpression change between each pair of samples . Forbrain-brain transcriptome comparisons, the number of suchgenes was equal to 34,488, while for brain-heart comparisons,this number almost doubled . Takentogether, all these findings on gene and transcript quantificationindicate the correctness of the transcriptome assembly.Transcriptome assembly and annotationOnce the expression quantification step was done, we annotatedthe obtained transcripts to evaluate the number ofbiologically relevant ones. We first identified a total of 141,950candidate coding regions using TransDecoder and obtainedinformation about known protein homologs and protein domains.Using the Trinotate pipeline for functional annotationof transcripts, we then detected 59,078 known transcriptsin our assembly that clustered into 22,251 genes. Finally,we explored the fraction of annotated genes with TPM > 0that are common between replicates. We retrieved a total of 18,229 genes with expression in all three replicates as well as2680 and 448 genes expressed only in brain and heart samples,respectively .Gene Ontology analysisDuring the annotation step, we identified a total of 11,482 genesfor which corresponding GO categories were described.In particular, we found 6696 genes involved in binding(including 2988 genes associated with protein binding and878 genes responsible for DNA binding), 3531 genes involvedin catalytic activity, and 576 genes associated with transporteractivity .For 10,769 annotated genes without assigned GO categories,we performed an additional analysis of their functionalroles. Among them, we found several large functional genegroups, including 1969 genes associated with the RVT_1(Reverse transcriptase) family, 1365 genes encoding zf-C2H2(zinc finger) protein domains, and 455 genes belonging to theendonuclease/exonuclease/phosphatase familyNeurotransmitter receptor genesA search for neurotransmitter receptors recovered a total of47 transcripts belonging to six classes (Table 2). All detectedtranscripts could be unambiguously attributed to particularclasses of receptors. Unexpectedly, we failed to detect anytranscripts of histamine receptors. Our blastn and blastx searchfor these genes in the available ranid genome and transcriptomedata resulted in no expressed histamine receptors in anysequenced cDNA data from any tissue. However, the genomeof R. temporaria was found to contain the full gene set ofhistamine receptor genes. This may indicate that the histaminepathway has very limited expression in the family Ranidae.Neurotransmitter receptor genesA search for neurotransmitter receptors recovered a total of47 transcripts belonging to six classes (Table 2). All detectedtranscripts could be unambiguously attributed to particularclasses of receptors. Unexpectedly, we failed to detect anytranscripts of histamine receptors. Our blastn and blastx searchfor these genes in the available ranid genome and transcriptomedata resulted in no expressed histamine receptors in anysequenced cDNA data from any tissue. However, the genomeof R. temporaria was found to contain the full gene set ofhistamine receptor genes. This may indicate that the histaminepathway has very limited expression in the family Ranidae.The information on neurotransmitters is of special interestbecause they are known to be involved in hypoxia responsein various organisms. G.E. Nilsson et al. foundthat levels of different neurotransmitters in the brain and otherorgans changed significantly upon exposure to hypoxia: theconcentrations of GABA increased, and those of glutamatedecreased in the crucian carp and the red-eared slider turtle, butnot in the hypoxia-intolerant species. The authors also foundthat the levels of serotonin, dopamine, and norepinephrineremained unchanged, although their synthesis is oxygen-dependent.This response probably involves not just an upregulationof neurotransmitter synthesis, but the rearrangement ofthe whole pathway, and thus the obtained transcriptome datawill be of particular use to elucidate this issue.In recent years, transcriptome analysis is increasingly usedfor amphibians, e. g., to study the effects of pathogens , insecticides ,or the changes occurring during metamorphosis . Many of those studies combine datafrom different tissues to obtain a more or less comprehensiveset of transcripts expressed in the most important organs. In this study, we sequencedand assembled the transcriptome of the Siberian frog R. amurensis.We also provided a quality assessment of the obtainedassembly and characterized the functional roles of annotatedtranscripts. The available information on amphibian transcriptomesis still limited; therefore, our dataset contributes to theunderstanding of genome functioning and evolution of amphibians.Moreover, the majority of the previously publishedtranscriptome assemblies for other species of the genus Rana,e. g., in I. Birol et al. (2015) and S.J. Price et al. (2015), areprobably not the best option for studying the mechanisms ofthe hypoxia tolerance in these species. Because these studiesdo not focus on hypoxia and are not based on hypoxia samples,the assembled transcriptomes might miss or under-representsome transcripts specific for hypoxia. In contrast, our workcreates a useful resource for studying the mechanisms of thetolerance of R. amurensis to hypoxia.The authors declare no conflict of interest.Bairoch A., Apweiler R. The SWISS-PROT protein sequence databank and its supplement TrEMBL in 1999. Nucleic Acids Res. 1999;27(1):49-54. DOI 10.1093/nar/27.1.49.Berman D.I., Bulakhova N.A., Meshcheryakova E.N. The Siberianwood frog survives for months underwater without oxygen. Sci. Rep.2019;9(1):13594. DOI 10.1038/s41598-018-31974-6.Berman D.I., Bulakhova N.A., Meshcheryakova E.N., Shekhovtsov S.V.Overwintering and cold tolerance in the moor frog across its range. Can. J. Zool. 2020;98(11):705-714. DOI 10.1139/cjz-2019-0179.Berman D.I., Leirikh A.N., Meshcheryakova E.N. The Schrenck newt is thesecond amphibian that withstands extremely low temperatures.Dokl. Biol. Sci. 2010;431(1):131-134. DOI 10.1134/S0012496610020171.Berman D.I., Leirikh A.N., Mikhailova E.I. Winter hibernation of theSiberian salamander Hynobius keyserlingi. J. Evol. Biochem. Physiol.1984;3(1\u20132):323-327. (in Russian)Berman D.I., Meshcheryakova E.N., Bulakhova N.A. The Japanesetree frog (Hyla japonica), one of the most cold-resistant species ofamphibians. Dokl. Biol. Sci. 2016a;471(1):276-279. DOI 10.1134/S0012496616060065Berman D.I., Meshcheryakova E.N., Bulakhova N.A. Extreme negativetemperatures and body mass loss in the Siberian salamander . Dokl. Biol. Sci.2016b;468(1):137-141. DOI 10.1134/S001249661603011X.Bickler P.E., Buck L.T. Hypoxia tolerance in reptiles, amphibians,and fishes: Life with variable oxygen availability. Annu. Rev. Physiol.2007;69(1):145-170. DOI 10.1146/annurev.physiol.69.031905.162529.Birol I., Behsaz B., Hammond S.A., Kucuk E., Veldhoen N., Hel-bingC.C. De novo transcriptome assemblies of Rana (Lithobates)catesbeiana and Xenopus laevis tadpole livers for comparativegenomics without reference genomes. PLoS One. 2015;10(6):e0130720. DOI 10.1371/journal.pone.0130720.Bryant D.M., Johnson K., DiTommaso T., Tickle T., Couger M.B.,Payzin-Dogru D., Lee T.J., Leigh N.D., Kuo T.-H., Davis F.G., BatemanJ. A tissue-mapped axolotl de novo transcriptome enables identificationof limb regeneration factors. Cell Rep. 2017;18(3):762-776. DOI 10.1016/j.celrep.2016.12.063.Camacho C., Coulouris G., Avagyan V., Ma N., Papadopoulos J.,Bealer K., Madden T.L. BLAST+: architecture and applications.BMC Bioinformatics. 2009;10(1):421. DOI 10.1186/1471-2105-10-421.Chen S., Zhou Y., Chen Y., Gu J. fastp: an ultra-fast all-in-one FASTQpreprocessor. Bioinformatics. 2018;34(17):i884-i890. DOI 10.1093/bioinformatics/bty560.Christenson M.K., Trease A.J., Potluri L.P., Jezewski A.J., Davis V.M.,Knight L.A., Kolok A.S., Davis P.H. De novo assembly and analysisof the northern leopard frog Rana pipiens transcriptome. J. Genomics.2014;2:141-149. DOI 10.7150/jgen.9760.Eddy S.R. Accelerated profile HMM searches. PLoS Comput. Biol.2011;7(10):e1002195. DOI 10.1371/journal.pcbi.1002195.Fu L., Niu B., Zhu Z., Wu S., Li W. CD-HIT: accelerated for clusteringthe next-generation sequencing data. Bioinformatics. 2012;28(23):3150-3152. DOI 10.1093/bioinformatics/bts565.Grabherr M.G., Haas B.J., Yassour M., Levin J.Z., Thompson D.A.,Amit I., Adiconis X., Fan L., Raychowdhury R., Zeng Q. Trinity:reconstructing a full-length transcriptome without a genome fromRNA-Seq data. Nat. Biotechnol. 2011;29(7):644. DOI 10.1038/nbt.1883.Hammond S.A., Warren R.L., Vandervalk B.P., Kucuk E., Khan H.,Gibb E.A., Pandoh P., Kirk H., Zhao Y., Jones M., Mungall A.J.,Coope R., Pleasance S., Moore R.A., Holt R.A., Round J.M.,Ohora S., Walle B.V., Veldhoen N., Helbing C.C., Birol I. The NorthAmerican bullfrog draft genome provides insight into hormonal regulation of long noncoding RNA. Nat. Commun. 2017;8:1433. DOI10.1038/s41467-017-01316-7.Katsura Y., Ikemura T., Kajitani R., Toyoda A., Itoh T., Ogata M.,Miura I., Wada K., Wada Y., Satta Y. Comparative genomics ofGlandirana rugosa using unsupervised AI reveals a high CG frequency.Life Sci. Alliance. 2021;4(5):e202000905. DOI 10.26508/lsa.202000905.Ma Y., Li B., Ke Y., Zhang Y., Zhang Y. Transcriptome analysis of Ranachensinensis liver under trichlorfon stress. Ecotoxicol. Environ. Saf.2018;147:487-493. DOI 10.1016/j.ecoenv.2017.09.016Mistry J., Chuguransky S., Williams L., Qureshi M., Salazar G.A.,Sonnhammer E.L.L., Tosatto S.C.E., Paladin L., Raj S., RichardsonL.J., Finn R.D., Bateman A. Pfam: The protein families databasein 2021. Nucleic Acids Res. 2021;49(D1):D412-D419. DOI 10.1093/nar/gkaa913.Nilsson G.E. Long-term anoxia in crucian carp: changes in the levelsof amino acid and monoamine neurotransmitters in the brain, catecholaminesin chromaffin tissue, and liver glycogen. J. Exp. Biol.1990;150(1):295-320. DOI 10.1242/jeb.150.1.295.Nilsson G.E., Lutz P.L., Jackson T.L. Neurotransmitters and anoxic survivalof the brain: a comparison of anoxia-tolerant and anoxia-intolerantvertebrates. Physiol. Zool. 1991;64(3):638-652. DOI 10.1086/physzool.64.3.30158198Nilsson G.E., Vaage J., Stensl\u00f8kken K.O. Oxygen-and temperaturedependentexpression of survival protein kinases in crucian carp(Carassius carassius) heart and brain. Am. J. Physiol. Regul. Integr.Comp. Physiol. 2015;308(1):R50-R61. DOI 10.1152/ajpregu.00094.2014Price S.J., Garner T.W.J., Balloux F., Ruis C., Paszkiewicz K.H.,Moore K., Griffiths A.G. A de novo assembly of the common frog(Rana temporaria) transcriptome and comparison of transcriptionfollowing exposure to Ranavirus and Batrachochytrium dendrobatidis.PLoS One. 2015;10(6):e0130500. DOI 10.1371/journal.pone.0130500.Qiao L., Yang W., Fu J., Song Z. Transcriptome profile of the greenodorous frog (Odorrana margaretae). PLoS One. 2013;8(9):e75211.DOI 10.1371/journal.pone.0075211.Robertson L.S., Cornman R.S. Transcriptome resources for the frogsLithobates clamitans and Pseudacris regilla, emphasizing antimicrobialpeptides and conserved loci for phylogenetics. Mol. Ecol.Resour. 2014;14(1):178-183. DOI 10.1111/1755-0998.12164Schatz M.C., Delcher A.L., Salzberg S.L. Assembly of large genomesusing second-generation sequencing. Genome Res. 2010;20(9):1165-1173. DOI 10.1101/gr.101360.109.Shekhovtsov S.V., Bulakhova N.A., Tsentalovich Y.P., Zelentsova E.A.,Yanshole L.V., Meshcheryakova E.N., Berman D.I. Metabolicresponse of the Siberian wood frog Rana amurensis to extremehypoxia. Sci. Rep. 2020;10(1):14604. DOI 10.1038/s41598-020-71616-4.Sim\u00e3o F.A., Waterhouse R.M., Ioannidis P., Kriventseva E.V., ZdobnovE.M. BUSCO: assessing genome assembly and annotation completenesswith single-copy orthologs. Bioinformatics. 2015;31(19):3210-3212. DOI 10.1093/bioinformatics/btv351.Song L., Florea L. Rcorrector: efficient and accurate error correction forIllumina RNA-seq reads. GigaScience. 2015;4(1):48. DOI 10.1186/s13742-015-0089-y.Storey K.B. Freeze tolerance in the frog, Rana sylvatica. Experientia.1984;40(11):1261-1262. DOI 10.1007/BF01946664.Storey K.B., Storey J.M. Molecular physiology of freeze tolerancein vertebrates. Physiol. Rev. 2017;97(2):623-665. DOI 10.1152/physrev.00016.2016.Streicher J.W. Wellcome Sanger Institute Tree of Life programme,Wellcome Sanger Institute Scientific Operations . The genome sequence of the common frog, Rana temporaria Linnaeus 1758. Wellcome OpenRes. 2021;6:286. DOI 10.12688/wellcomeopenres.17296.1.Swenson E.R. Hypoxia and its acid-base consequences: from mountainsto malignancy. Adv. Exp. Med. Biol. 2016;903:301-323. DOI10.1007/978-1-4899-7678-9_21. PMID: 27343105The Uniprot Consortium. UniProt: the universal protein knowledgebasein 2021. Nucleic Acids Res. 2021;49(D1):D480-D489. DOI10.1093/nar/gkaa1100.Xu Y.G., Chai L.H., Shi W., Wang D.D., Zhang J.Y., Xiao X.H. Transcriptomeprofiling and digital gene expression analysis of the skinof Dybowski\u2019s frog (Rana dybowskii) exposed to Aeromonas hydrophila. Appl. Microbiol. Biotechnol. 2017;101(14):5799-5808.DOI 10.1007/s00253-017-8385-3.Yang W., Qi Y., Bi K., Fu J. Toward understanding the genetic basis ofadaptation to high-elevation life in poikilothermic species: a comparativetranscriptomic analysis of two ranid frogs, Rana chensinensisand R. kukunoris. BMC Genomics. 2012;13:588. DOI 10.1186/1471-2164-13-588.Zhao L., Liu L., Wang S., Wang H., Jiang J. Transcriptome profilesof metamorphosis in the ornamented pygmy frog Microhyla fissipesclarify the functions of thyroid hormone receptors in metamorphosis.Sci. Rep. 2016;6:27310. DOI 10.1038/srep27310."} +{"text": "Nash, J. D., and Newberg, A. (2013). This has been corrected to Nash et al. . Toward a unifying taxonomy and definition for meditation. Front. Psychol. 4:806. doi: 10.3389/fpsyg.2013.00806.In the references section, The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Translational Psychiatry 10.1038/s41398-021-01774-0, published online 10 January 2022Correction to: The original version of this article unfortunately contained a mistake. It appears the authors forgot to convert a citation into the correct format and consequently omitted it from the references. The correct reference is: Velazquez-Hernandez, G, Sotres-Bayon, F. Lateral habenula mediates defensive responses only when threat and safety memories are in conflict. eNeuro. 2021;8;ENEURO.0482-20.2021. 10.1523/ENEURO.0482-20.2021. The original article has been corrected."} +{"text": "This issue of the Vavilov Journal of Genetics and Breeding is composed of reports of top Russian breeders delivered at the scientific session of the RAS Departmentof Agricultural Sciences \u201cScientific support of the efficientdevelopment of crop breeding and seed production in theRussian Federation\u201d held in Moscow on December 7, 2020.This topic was chosen deliberately, as the food security concept in the Russian Federation determines the key directionsand features of the modern development of Russian breeding.They involve the understanding and comprehensive analysisof breeding trends and the determination of prospects, particularly, in connection with import substitution1 and produceof next-generation cultivars.The issue starts with the article by B.I. Sandukhadze etal. \u201cScientific breeding of winter bread wheat in the Non\u0421hernozem zone of Russia: the history, methods and results\u201d.It reviews the main steps and achievements of winter common(bred) wheat (Triticum aestivum L.) in the region throughoutone century of scientific breeding. It shows that breeders\u2019efforts increased the yield of wheat cultivars to 14.0 t/ha,which is nearly ten times as high as in cultivars of early stepsof scientific breeding in the central Non-Chernozem Area.Few residents of Moscow and Moscow region are aware ofthe \u201cwhite spot\u201d issue , successfully solved by prominent Russian breeder V.E. Pisarev byusing early maturity cultivars from East Siberia. By now, cultivars produced by breeders of the FSC \u201cNemchinovka\u201d haveensured the provision of the Non-Chernozem Area, a denselypopulated region of Russia, with locally produced food wheatgrain and got the local population used to eating white bread.The Russian Federation is self-sufficient in producing not onlywheat, barley, or oats but also rice .Area under grain legumes is second to cereals in Russia.They have accompanied cereals since the earliest steps of domestication on fields of ancient agriculturists. They diversifiedhuman diet and supplied domestic animals with high-proteinfodder. The breeding of grain legumes is reviewed by V.T. Sinegovskaya \u201cScientific provision of an effective developmentof soybean breeding and seed production in the RussianFar East\u201d and by V.I. Zotikov, S.D. Vilyunov \u201cPresent-daybreeding of legumes and groat crops in Russia\u201d. They notethat soybean is becoming a crop of strategic importance for Russia and that groat crops constantly rank high in the dietof its inhabitants.By import substitution we mean the substitution of imported goods andservices for domestic ones. It implies the slowdown in the share of foreignmanufacturers in the market and timely satisfaction of demand with domesticproducts.The article by V.M. Lukomets et al. \u201cModern trends inbreeding and genetic improvement of sunflower varietiesand hybrids at VNIIMK\u201d is dedicated to the breeding of themain oil plant in the Russian Federation. The Pustovoit AllRussian Research Institute of Oil Crops (VNIIMK), alongwith the Yuriev Plant Production Institute excels in the breeding of sunflowerand other oil crops in the former Soviet Union.The breeding of sugar beet, the main source of sugar inEurope, is considered by S.D. Karakotov et al. \u201cModern issuesof sugar beet (Beta vulgaris L.) hybrid breeding\u201d. The paperpresents the results of monogerm varieties and successful application of molecular methods for testing the bred materialof sugar beet.The imbalance in fodder production that has existed in Russia for many years remains unresolved despite all the efforts ofplant breeders. Even the considerable reduction in livestock inagricultural companies (agrofirms) and redistribution of largevolumes of animal husbandry to private subsidiary farms (upto 50 % on the average) had no effect . Thearticle by V.M. Kosolapov et al. \u201cFundamentals for foragecrop breeding and seed production in Russia\u201d is dedicatedjust to this burning problem and potential ways to solve it. A series of three papers is dedicated to the breeding offruit and small fruit crops, essential for balanced nutrition.It includes articles by E.A. Egorov \u201cGrape breeding is a keylink in the development of the grapes and wine-making industry\u201d, I.M. Kulikov et al. \u201cScientific support of small fruitgrowing in Russia and prospects for its development\u201d, andA.V. Ryndin et al. \u201cSubtropical and flower crops breeding atthe Subtropical Scientific Centre\u201d. At present, import substitution draws attention to new natural sources of vitamins and biologically activesubstances and to the breeding of domestic subtropical andflower plantsThe progress in the breeding of medicinal and essentialoil plants in Russia is considered by I.N. Korotkikh et al.\u201cBreeding of medicinal and essential oil crops in VILAR:achievements and prospects\u201d. This field became particularlyimportant with regard to the sanctions, the ensuing shortageof herbal medicinal materials, and their poor quality, failingto meet the requirements of the present-day pharmaceuticalindustry.Russian seed growers do not provide sufficient volumesof production of seeds of vegetable crops\u2019 domestic varieties . Modern breeding is based mainly onthe gene pool at hand to involve older high-yielding varietiesinto breeding and improve them. The article by Yu.V. Fotev etal. \u201cGenetic resources of vegetable crops: from breeding nontraditional crops to functional food\u201d follows traditional VIRthemes. It considers the introduction of untraditional crops inRussia in the context of the greatly requested area: their usein functional nutrition .The issue is concluded by N.P. Goncharov\u2019s review \u201cScientific support to plant breeding and seed production in Siberiain the XXI century\u201d. It emphasizes the importance of breeding activity in the development of Russian economy and thenecessity for the preservation of still existing research institutions and units of abolished Breeding Centers in Siberia. Inthe contrary case, the consistency of breeding works in theregion will disappear, and the unique breeding material createdby generations of Russian scientists in research and breedinginstitutions will be lost beyond retrieval. The following problems are especially acute: Why cannot the federal and regionalgovernments protect their intellectual property and preservebiodiversity of cultivated plants? What and who hampers?These issues, typical of Siberia, as well as the availability ofskilled staffing concern other regions of Russia, too.Several articles in the issue mention the necessity of theimmediate solution of urgent tasks concerning the trainingof breeders in higher schools as a major component of foodsecurity in Russia. Nothing changes for centuries. In the endof the 19th century, A.S. Ermolov (1891) incriminated thebackwardness of Russian agriculture to the absence of anagricultural education system and to the shocking ignoranceof science among peasants.It is pertinent to make a point about the publication policyof the Ministry of Education and Science and Presidium ofthe Russian Academy of Sciences. It is a sore point for notonly agrarians but also the entire Russian academic community. For an unknown reason, the governmental strategy ofimport substitution does not apply to the scientific publishingactivities. The principal journal \u201cSelektsiya i Semenovodstvo\u201d(Breeding and Seed Production) has ceased to be published.Specialized agricultural journals on particular crops or groupsof crops demand a nation-specific policy. A.N. Engelhardt(1987) wrote that the agricultural science in its broad sense haspronounced \u201cnational\u201d features: \u201cThere is no Russian, English,or German chemistry; there is only one chemistry for the entireworld; but agronomy may be Russian, or English, or German, orelse. <\u2026> We should create Russian agricultural science of ourown, and it can be created only by combined efforts of scientistsand practicians, and there should be academically trained practicians in between\u201d (p. 190).It was repeatedly noted that different branches of Russian science need their own national platforms forcommunication and effective exchange of information. Inparticular, A.V. Yurevich and I.P. Tsapenko (2013) state thatmost Russian papers on socio-humanistic sciences are unfit forinternational journals not because of their flaws but becauseof the national specificity of their content. However, to bringstudies in line with the themes of international journals means to detach them from urgent Russian problems and to make thesociety think that the money of Russian taxpayers is spent invain. Hence, the more patriotic is this or that branch of science and the more is it directed to the solution of domestictasks, the less it fits into the international context. Even by theexample of highly employable Vavilov\u2019s studies we see thatmost of them are beyond the scope of interests of our Westerncolleagues, although they are conceptually important for thepresent-day global science. Neither Ministry of Education &Science, nor the current Presidium of the RAS see room forRussian journals in the world academic community. Howeversad it be, the task of any import substitution seems costlyto Russian officials; therefore, the publication policy is theworst weakness of Russian science. We expressly indicatethat the intellectual property of Russian scientists or Russiais not protected in publications in top Western journals, andit is often unaccessible for the scientific community in thiscountry For many years, breeding in Russia has been distinguishedby the widespread use of genetic knowledge. Breeding and genetics schools are held in Siberia on a regular basis since 1976. We can also mention the All-Siberia program\u2018Diallel Analysis\u2019 . Unfortunately,the gap between breeding and modern molecular biology isstill unplugged.Academician I.I.Artobolevskiy (1967) believed on reasonable grounds that the promotion of scientific achievements isa first-order duty of scientists. We try to find out why leadingbreeding schools in Russia insufficiently and reluctantly employ recent discoveries in molecular biology, biotechnology,and IT technologies. Presently, significant breeding achievements reached by using molecular methods exist in Russia.Promising studies opening up fresh opportunities for breedingare being conducted. In particular, the Institute of Cytologyand Genetics (Novosibirsk) took part in the assembly of thewheat genome . Here we are at the verybeginning, since the information on the genome sequence fromone accession is not sufficient to capture the whole spectrum ofdiversity in a gene pool responsible for phenotypic variation,plasticity, and environmental adaption. The de novo construction of a pan-genomes for cultivated plants is a mandatorystep after the establishment of reference genome sequencesfor them. Obviously, it will be the key step in future breeding . The low sequencing depths evenfor wheat, a staple crop in Russia, still limit the broad use ofpan-genomic analysis .Several important problems concerning IT technologies inbreeding were discussed in the previous issue of the VavilovJournal of Genetics and Breeding, No. 1, 2021; so, we willnot touch upon them. Nevertheless, the technological gapbetween the performance of genomic analysis and phenotypical description of plants is still large. In breeding a newvariety, one should rest upon today\u2019s perspectives and takeinto consideration both current requirements and remoteprospects. Certainly, recent technological achievements incrop genomics generate new opportunities in the detection of genetic variations of traits important for breeding and permitone to create new-generation varieties. They come to the aidof breeders and allow fast, exact, and mass-scale descriptionof plant phenotypes be it in the field or under laboratory conditions.Functional genomics is a key to molecular breeding andbasement for the development of diagnostic markers forgene introgression and molecular marker-assisted selection.Although the cloning of functional genes in crops was a slowprocess, few genes were cloned by conventional \u201cpositionalcloning\u201d. On the other hand, high-throughput PCR-basedKASP (Kompetitive Allele-Specific PCR) markers are helpful in the use of SNP arrays for high-densitygenotyping of wheat and related species , as wellas in the annotation and introduction of functional genes. It isevident, though, that the role of money in the application ofthese methods to ordinary breeding is not the least, and theywill not become widespread, inexpensive, and routine beforelong .A characteristic feature of modern economy, including agriculture, is the predominance of novelties as a factor supportingcompetitiveness and economic advance in the long run. Thequestion whether molecular biology can serve as a pioneeringfactor in plant breeding is open. Presently, prebreeding is an applicationdomain of up-to-date molecular methods. However, it is differently viewed by molecular biologists , geneticists ,and breeders . In contrast, their viewson breeding itself are similar. Molecular methods are currently used toaccelerate selection in the stabilization of breeding material, its homozygotization , and so on. The raise of promising breeding materialcan be accelerated by removing the germplasm of wild species from the progeny of introgression hybrids ; thereby, fragments of alien genetic material canbe reduced in the genome of a species to breed . This process is aimed at the reduction of adverseeffects of concomitant genetic material transferred with thetarget genes. It has been demonstrated that molecular markersallow efficient selection for dwarfism , early ripening , and many other traits. Meanwhile, the breeding for suchimportant traits as crop productivity and quality of productionis still conducted by conventional methods.The assessment of the efficiency of plant genome editing byCRISPR/Cas technologies, operating with single functionalgenes, presents an acute and complicated problem . We do not know whether this one-gene manipulation is a breakthrough technology in breeding, which dealswith hundreds of functional genes. Generally, there are nosingle genes whose replacement would result in sustainableprogress. In addition, the CRISPR-edited plants have highsomaclonal variability. Nevertheless, the tools and methodsfor plant transformation clearly alter phenotypes, being ableto benefit from gene overexpression and other manipulationsformerly inaccessible for breeders .Serious progress based on advanced technologies occursin large seed producing companies, where breeders, geneticists, and molecular biologists work under the same roof. Forinstance, DuPond-Pioneer developed the Seed ProductionTechnology concept, which successfully combines conventional hybridization with transgenic methods of raising malesterile (MS) lines, hybrid selection, and MS line support . The producing of nuclear MS lines by genomeediting illustrates the applicability of this concept to wheat. Several more breakthrough technologiesfor hybrid creation are reviewed by Chen et al. (2021). Thequestion remains open how soon this approach will becomeroutine for breeding institutions.Breeders\u2019 work was scrutinized repeatedly. Nevertheless,we do not know how profoundly paradigm shifts in breeding affect the speed of the breeding process andachievement of goals. It is doubtless that in recent decadestraditional schemes involving hybridization and, to a muchlesser extent, chemical and radiational mutagenesis contributed much to crop improvement. However, the globalization epoch necessitates the search for new groundbreakingmethods. Many seemingly revolutionary methods came andwent from the scientists\u2019 toolkit and left an imprint only inbreeding history records. Old-timers remember monosomiclines, which allowed the produce of varieties using the methodof limited recombination and rapidly \u201crepair\u201d unique varieties.To tell the truth, the development of each from monosomiclines took 15\u201320 years. During this time, conventional breeders replaced the entire range several times and produced newremarkable varieties. It is natural that this approach did notprovide a single commercial variety despite the huge scopeof work . Protoplasts , isoenzymes, and many others, looking modern in their days,did not change the breeding paradigm. It is worth mentioning that some breakthrough projects, such as domesticationor green revolution (improvement of the range of wheat andrice varieties) were implemented by conventional breeding,and they were based on the choice of key traits regardless ofthe genetic and/or molecular mechanisms of their inheritance.One of the targets of modern technologies is the accelerationof new variety breeding and introduction. For some reason,the powerful take it to mean the shortening of their producing time and make it the corner stone. It is a fringe concern,because the terms of variety submission to the Plant StateTasting System are insignificant in major breeding institutions,which produce series of new varieties massive. Present-daymolecular Stakhanovites are nothing new. It is pertinent torecall the anecdote about the producing of cv. Lutescens 1163common wheat by T.D. Lysenko et al. (1935) within 2.5 yearsby using know how: greenhouses and hybrids at hand insteadof original accessions. It is sad that Stakhanovite methods ofbreeding are becoming nationwide again in the 21st century.N.I. Vavilov likened a geneticist to a creator and stated thathe \u201cmust act as an engineer; not only is he obliged to investigatehis construction material, but he can and should construct newliving species\u201d2. The tasks are basically the same at present, itis the toolkit that has changed and expanded.It is well known that genetics and breeding deal with heredity and variability and thus they interpenetrate. Breedingemploys the laws of inheritance discovered by genetics, andgenetics, in turn, obtains and generalizes data from breeding. While geneticistswere seeking ways to overcome the abyss between geneticsand breeding , molecular biology justrevoked many of these problems . We have already mentioned that breeding received newtools. They provoked controversy as to whether they shouldbe used extensively. Certainly, to know and master them isa must. However, business has an increasing share in thescience of the 21st century. To conduct a modern study is abusiness operation. To obtain results is a business operation.To publish them in top-rated journals is a business operation.In the last case, to make a successful (in the eye of the Ministry of Education and Science) publication one should employup-to-date expensive equipment, not necessary for the workitself. The organization of the breeding process is a businessas well, since the development of crop production is increasingly considered only as the delivery of agricultural services.This situation reminds the notorious \u201carms race\u201d, and we canwin it by promoting our own rules.The applied aspect of Russian science progressively increases . Breeding in many European countries, including former COMECON members, is becomingprivate business under the pressure of multinational groupsof agrochemical companies. The consequences are the listof top-priority research fields, the mainstream innovationalpractice of support by the Russian Science Foundation, the technological orientation of sections of the national Naukaproject, and such. The national foundations of the RussianFederation do not imply considerable support of academicstudies in breeding, solely the mastering and preservation ofskills and technologies. Therefore, the search for alternativelarge sources of support for agricultural sciences, including21st century breeding, is of paramount importance.To conclude, we mention that breeding in the 21st centuryis directly associated with one of the global challenges, starvation. The 22nd session of the UN Food and AgricultureOrganization of October 31, 1996, adopted the so-called RomeDeclaration on World Food Security3, whose purpose was tohalve the number of the starving on the Earth by 2015. In fact, as reported by the German philanthropy organization Welthungerhilfe, the number of thestarving had increased to one billion by 20204. With the currentslow progress in increasing crop yields, 0.8 to 1.0 % annually,wheat, rye, and corn cannot be produced in quantities sufficientfor the solution of the starvation problemThus, varieties play an essential role in improving theperformance of global agricultural industry; therefore, breeders are seeking new sustainable, efficient, and cost-effectivemethods to produce new varieties. One of the major objectivesof this issue of the Vavilov Journal of Genetics and Breedingis the thorough consideration of this task.Abd-Elsalam K.A., Lim K.T. Can CRISPRized crops save the globalfood supply? In: CRISPR and RNAi Systems: NanobiotechnologyApproaches to Plant Breeding and Protection. Elsevier, 2018. DOI10.1016/B978-0-12-821910-2.00006-0.Adonina I.G., Timonova E.M., Salina E.A. Introgressive hybridization of common wheat: results and prospects. Russ. J. Genet. 2021;57:2590. 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Developmentof a novel recessive genetic male sterility system for hybrid seedproduction in maize and other cross\u2010pollinating crops. Plant Biotechnol. J. 2016;14(3):1046-1054. DOI 10.1111/pbi.12477.Yurevich A.V., Tsapenko I. P. Once again on the assessment of the Russian contribution to world science. In: Science. Innovation. Education.Vol. 13: Languages of Slavic culture. 2013;60-83. (in Russian)Zilke R.A. Thirty years of the genetic breeding school. Vestnik Novosibirskogo Gosudarstvennogo Agrarnogo Universiteta = Bulletin ofthe Novosibirsk State Agrarian University. 2005;2:11-17. (in Russian)"} +{"text": "Nature Communications 10.1038/s41467-021-23585-z, published online 14 June 2021.Correction to: Phys. Rev. B99, 224423 (2019)\u201d. The correct form of ref. 20 is: \u201cAgrapidis, C. E., van den Brink, J. & Nishimoto, S. Field-induced incommensurate ordering in Heisenberg chains coupled by Ising interaction: model for ytterbium aluminum perovskite YbAlO3. Phys. Rev. B99, 224423 (2019)\u201d.The original version of this Article contained an error in ref. 20, which was incorrectly given with the wrong title as: \u201cAgrapidis, C. E., van den Brink, J. & Nishimoto, S. Ground state and low-energy excitations of the Kitaev-Heisenberg two-leg ladder. This has been corrected in the PDF and HTML versions of the Article."} +{"text": "Plant diseases cause signif icant economic losses in agriculture around the world. Early detection, quantif ication and identif ication of plant diseases are crucial for targeted application of plant protection measures in crop production. Recently, intensive research has been conducted to develop innovative methods for diagnosing plant diseases based on hyperspectral technologies. The analysis of the ref lection spectrum of plant tissue makes it possible to classify healthy and diseased plants, assess the severity of the disease, differentiate the types of pathogens, and identify the symptoms of biotic stresses at early stages, including during the incubation period, when the symptoms are not visible to the human eye. This review describes the basic principles of hyperspectral measurements and different types of available hyperspectral sensors. Possible applications of hyperspectral sensors and platforms on different scales for diseases diagnosis are discussed and evaluated. Hyperspectral analysis is a new subject that combines optical spectroscopy and image analysis methods, which make it possible to simultaneously evaluate both physiological and morphological parameters. The review describes the main steps of the hyperspectral data analysis process: image acquisition and prepro cessing; data extraction and processing; modeling and analysis of data. The algorithms and methods applied at eachstep are mainly summarized. Further, the main areas of application of hyperspectral sensors in the diagnosis of plantdiseases are considered, such as detection, differentiation and identif ication of diseases, estimation of disease severity,phenotyping of disease resistance of genotypes. A comprehensive review of scientif ic publications on the diagnosis ofplant diseases highlights the benef its of hyperspectral technologies in investigating interactions between plants andpathogens at various measurement scales. Despite the encouraging progress made over the past few decades in monitoringplant diseases based on hyperspectral technologies, some technical problems that make these methods diff icultto apply in practice remain unresolved. The review is concluded with an overview of problems and prospects of usingnew technologies in agricultural production Plant diseases cause crop losses, reduce the quality ofagricultural products and can even threaten human health.Farmers need modern and effective tools for early detectionand identification of plant diseases .Traditional diagnostic methods such as visual assessmentand microbiological laboratory analysis are time-consumingand labor-intensive, which limits their application in largescalefarms.Currently, new non-invasive methods for diagnosing plantdiseases using sensor technologies, robotics, computer visionand machine learning are rapidly developing .These methods are high throughput and provide a real-timesupport for assessing a range of physiological parameters. A large amount of information obtainedfrom modern sensors is transformed into new knowledgeusing computer data processing and modeling, reducing thedistance from fundamental science to practical implementation. Newapproaches allow, due to automation, to significantly speedup the diagnosis of diseases and increase its accuracy byeliminating the human subjectivity .At present, a variety of imaging methods are being usedfor plant diseases detection, such as fluorescence imaging,thermal infrared imaging, visible RGB imaging, imagingspectroscopy and other techniques .Among them, hyperspectral imaging technique comeswith numerous advantages . According to the Scopusstatistics, there are 412 relevant papers from 2005 to 2020where \u2018plant disease\u2019 and \u2018hyperspectral\u2019 are used as keywords for the search . Hyperspectral analysis combinesoptical spectroscopy and image analysis methods,allowing both physiological and morphological parametersto be evaluated simultaneously.The aim of the paper is to provide the reader with anoverview of modern technologies for the diagnosis of plantdiseases based on the analysis of hyperspectral images. Thefirst part of the article discusses the main principles and toolsof hyperspectral technologies. Next, algorithms and methodsfor analyzing hyperspectral images are described. Further,the main areas of application of hyperspectral sensors inthe diagnosis of plant diseases are considered. The paper isconcluded with some problems and prospects of using newtechnologies.Interaction of light(electromagnetic radiation) and plantsLight can interact with plant tissue in the following ways:reflection, scattering, absorption and transmission. Thereflectance characteristic of a plant results from the biochemicalcompounds present in the leaves, and the physicalcharacteristics of leaves . The interactionbetween light and plants also depends on the wavelength. Inthe visible wavelength range (400\u2013700 nm), the surface ofthe plant has a low reflectivity due to the absorption of lightby photosynthetic pigments . In the near infrared (700\u20131100 nm), the reflectanceincreases due to light scattering in the intercellularspace. In the short wave infrared range (1100\u20132500 nm),healthy plants have a low reflectance due to the absorptionof light by water, proteins and other carbon components. The green color of the leaf is consistentwith the characteristic reflection peak at 550 nm.Spectral profiles of healthy and diseased plants can differ.As a result of the impact of biotic and abiotic stressors, thebiochemical composition of plant tissues changes, whichis reflected in the change in the color and shape of leaves,transpiration rate, canopy morphology, and, consequently,in the spectral characteristics of plants . Moreover, each individual interaction of a plant anda pathogen has certain spatial and temporal dynamics, andthese processes affect different ranges of the electromagneticspectrum. For example, a change in photosynthetic activitycaused by pathogens leads to a change in reflectivity in thevisible range of the spectrum. Changes at the cellular levelhave a large impact on the near infrared spectrum. Tissuenecrosis leads to increased reflection in the shortwave infraredrange .Such relationships between cause and consequence canbe used to study the biochemistry of plants and to performcontrolled experimentsHyperspectral sensors and platformsThe basic principle of hyperspectral sensors is comparableto the principle behind RGB and multispectral cameras . All these systems measure the amount oflight reaching the sensor and store the information. UnlikeRGB cameras or multispectral cameras, a hyperspectral sensor measures up toseveral hundred bands of the electromagnetic spectrum inthe wavelength range of the sensor. Each of these spectralbands measures only a few nanometers of the electromagneticspectrum, leading to a high spectral resolution of thehyperspectral sensor.There are two main types of sensors: image sensors andnon-imaging sensors. Non-imaging sensors measure theaverage reflectance spectrum in a certain area of a surfacewithout storing spatial information. The size of the averagingarea depends on the focal length, angle of view and distanceto the object. Most non-imaging sensors are portable and donot require complicated measurement platforms. They havea wide spectral range (300\u20132500 nm), a high spectral resolution(1\u20133 nm), and low weight (1\u20135 kg). The most popularamong them are spectrometers ASD FieldSpec , SVC , ImSpector .These devices are widely used in laboratory, greenhouse andfield conditions . There are also micro-spectrometers such asthe STS-VIS spectrometer suitablefor use with UAVs . Since earlysymptoms of plant disease often appear below 1 mm, theirdetection with spectrometers is limited. This is due to theaveraging of the spectrum of healthy and diseased tissue inthe measurement area .Hyperspectral image sensors form a spectral profile foreach individual pixel, thereby combining spectral and spatialresolution. The resulting image is a three-dimensional dataarray (hypercube) containing two dimensions of spatialinformation and additionally one dimension of spectralinformation. Depending on the type of sensors used, thereare four ways to obtain a hypercube of data : whiskbroom,push-broom, spectral scanning, and snapshot .Hyperspectral image sensors usually cover a limited spectralrange: VNIR (300\u20131000 nm) or SWIR (1000\u20132500 nm)with a spectral resolution of 1\u20137 nm. Spatial resolutionranges from micrometers to centimeters depending on thedistance to the object and sensor characteristicsIn the case of using point or line scanning sensors , it is necessary to move the object orthe camera to register the spectrum of each individual pointor line. In scientific research, the most commonly used scanningcameras are Specim ,Headwall , Photonfocus, Pika L . Most hyperspectral scanning cameras in the laboratoryare installed on specialized mobile platforms thatprovide linear movement and stabilization of the camera. Stationary railsystems are used in greenhouses .Vehicles orUAVs areused in the field. The disadvantage of scanning sensors isthe relatively long image acquisition time, depending on thesize of the measured area, which complicates the shooting ofmoving objects. This disadvantage is eliminated in portableSpecim IQ camera with a built-in scanner .Spectral scanning sensors use LCTF filters that passonly certain wavelengths changing rapidly during shooting. These sensorscreate 2D spatial images for each wavelength in the spectralrange. Their use does not require moving the object orcamera to obtain a hypercube. The acquisition time is mainlydependent on the exposure time, which is generally fasterthan point or line scans. If the object is moving, then thismeasuring principle can lead to inconsistent spectra, sincethe individual bands are observed at different times.Recently, snapshot sensors that do not require scanningan object to obtain a hypercube have been developed. Theyuse the mosaic principle of conventional RGB cameras.These sensors provide a significantly higher image recordingrate, but lower spatial resolution compared to traditionalones. Well-known cameras of this type are Rikola, Senop, Ultris, FireFleye .The compact size, short image acquisition time and theability to create a sequence of hyperspectral images of amoving object make them optimal for use in UAVs .From the data analysis perspective the use of multi-scaledatasets of hyperspectral images, characterized by a hugeamount of data with a high level of collinearity, is a verychallenging, emerging topic that requires non-trivial solutions.To face this challenge, the methods of discriminantand cluster analysis, machine learning, and neural networkshave been successfully adopted .Available software tools for hyperspectral image analysisprocess are ENVI (Research Systems Inc.), MATLAB (TheMath-Works Inc.), Python (Python Software Foundation),R (R Software Foundation).The hyperspectral image analysis process usually includesthe following steps : (1) image acquisition andpreprocessing, (2) data extraction and processing, (3) datamodeling and analysis.Image acquisition and preprocessingThe first important step in the analysis of plant diseases is toobtain high-quality hyperspectral images that meet the objectivesof research. The right choice of sensors and platforms,the correct setting of the spatial and spectral resolution,lighting scheme, scan rate, frame rate and exposure time areprerequisites for obtaining accurate results .The next step is image preprocessing, which includes calibrationand spectrum correction. The goals of the calibrationprocess are to standardize the spectral and spatial axes of thehyperspectral image, evaluate accuracy and reproducibilityof the acquired data under different operating conditions,eliminate curvature effect and instrumental errors .The standard practice is reflection calibration, which usestwo reference images, black and white. The black imageis acquired when the camera lens is completely coveredwith its opaque cap. The white reference image is obtainedusinga white surface board (e. g. Teflon) with a reflectivityof about 99.9 % to obtain the highest possible intensity foreach pixel at each wavelength. These two reference imagesare then used to correct the raw hyperspectral images byusing the following equation:where R is the corrected hyperspectral image, IS is the rawhyperspectral image, ID is the dark image, and IW is thewhite reference image.To eliminate the effect of surface curvature, spectralimagenormalization , adaptive sphericaltransform or Lambert transform are used during calibration.The goal of spectrum correction is to improve imagequality . For example, smoothing algorithms, as well as Fourier and wavelet transforms,are used to reduce noise from the spectral data. The first andsecond derivatives are used to correct the shift of the spectrumbaseline. Multiplicative scattering correction (MSC)and standard normal variate (SNV) are used to reduce thespectral variability due to scattering.Data extraction and processingAt this step of hyperspectral image analysis process, imagesegmentation is performed and features are selected forfurther analysis.Image segmentation is used as a pre-processing step andis typically performed before the formal spectral analysisin order to extract the target objects from the backgroundor form a mask for the formation of the region of inte rests (ROIs) for further information extraction. The followingsegmentationmethods are used: threshold-based ; K- means ; watershedalgorithm ; edge detection .Feature extraction can be considered to be the most importantstep in hyperspectral-based classification. Its goalis to extract and form new feature vectors for plant diseasedetection by combining and optimizing the spectral, spatialand texture features, then feed them to a set of classifiers ormachine learning algorithms.Vegetation indices (VI) or disease indices (DI) can be usedas features . In this case, only a smallnumber of wavelengths are required for analysis. When analyzingthe entire spectrum, the following methods are used toreduce the dimension and eliminate autocorrelations: principalcomponent analysis; minimum noise fraction algorithm;linear discriminant analysis; stepwise discriminant analysis;partial least square discriminant analysis .Data modeling and analysisThe last step in image analysis is to select a model and applyit to the data. Depending on the objectives of the study,these can be classification models (for diagnosing and differentiatingdiseases), or regression models .The most commonly used models are:\u2022 classification models of machine learning and neuralnetworks: spectral angle mapper, support vector machine,k-nearest neighbor, maximum likelihood ; \u2022 regression models: multiple linear regression, binary logisticregression, partial least squares regression, Dirichletaggregation regression .Areas of application of hyperspectral technologiesin diagnostics of plant diseasesThe main tasks in the diagnosis of plant diseases are detection,differentiation, identification, assessment of the diseaseseverity, assessment of the genotypes disease resistance.These tasks are solved at various levels of organization ofliving systems in the corresponding measurement scales.Measurements at the cellular or tissue scales are carriedout in laboratories using hyperspectral microscopes to observefungal spores and detect metabolic changes in tissuescaused by plant-pathogen interactions. Experiments at thecellular level are usually carried out in the context of fundamentalresearch and to some extent for the identificationof pathogens and the assessment of genotype resistance.Measurements at the level of individual organs and at the level of the whole plant are carriedout in laboratory, greenhouse or field conditions withthe aim of early detection and differentiation of the diseaseCanopy-level measurements are more often applied inplant disease mapping and severity assessment.Below is a brief overview of scientific publications onhyperspectral technologies in plant diseases diagnostics inthe coDisease detectionThe aim of disease detection is to differentiate healthy andinfected plants. In this case, the subject of research is onlyone specific disease, its symptoms and dynamics.A study of Mahlein et al., 2019a compares the feasibilityof different sensors to characterize Fusarium head blight.Under controlled conditions, time-series measurementswere performed with infrared thermography, chlorophyllfluorescence imaging, and hyperspectral imaging. Infraredthermography allowed the visualization of temperaturedifferences within the infected spikelets beginning 5 daysafter inoculation. Also, on the 5th day, a disorder of thephotosynthetic activity was confirmed by chlorophyll fluorescenceimaging of spikelets. Pigment-specific simple ratioderived from hyperspectral imaging allowed discriminationbetween Fusarium-infected and non-inoculated spikelets onthe 3rd day. Support vector machine method was used forclassification. The classification accuracy was 78, 56 and78 %, respectively.A study of Abdulridha et al., 2019 compares two methodsfor detecting citrus canker with hyperspectral imaging. In thelaboratory, a hyperspectral (400\u20131000 nm) imaging systemwas utilized for the detection of citrus canker at several diseasedevelopment stages by using two classification methods: (i) radialbasis function (RBF) and (ii) k-nearest neighbor (KNN).The same imaging system mounted on a UAV was used todetect citrus canker on tree canopies in the orchard. Theoverall classification accuracy of the RBF was higher than the KNN method fordetecting canker in leaves. Among the 31 studied vegetationindices, the water index (WI) and the Modified ChlorophyllAbsorption in Reflectance Index (ARI and TCARI 1) moreaccurately detected canker in laboratory and in orchardconditions, respectively. The UAV-based technique achieved100 % classification accuracy for identifying healthy andcanker-infected trees.Diseases identif ication and differentiationIn disease identification, the goal is to determine the typeof pathogen affecting the plant. The subject of research isseveral types of diseases, their distinctive features.Mahlein et al., 2013 developed specific spectral diseaseindices (SDIs) for the differentiation of diseases in crops.Sugar beet plants and three leaf diseases Cercospora leafspot, sugar beet rust and powdery mildew were used asmodel system. Hyperspectral signatures of healthy anddiseased sugar beet leaves were assessed with a nonimagingspectroradiometer at different development stagesand disease severities of pathogens. Significant and mostrelevant wavelengths and two band normalized differencesfrom 450 to 950 nm, describing the impact of a disease onsugar beet leaves, were extracted from the data-set usingthe RELIEF-F algorithm. To develop hyperspectral indices,the best weighted combination of a single wavelength anda normalized wavelength difference was searched. Healthysugar beet leaves and leaves, infected with Cercospora leafspot, sugar beet rust and powdery mildew were classifiedwith a high accuracy and sensitivity .A study of Bohnenkamp et al., 2019 establishes a methodfor detecting and distinguishing between brown rust (Pucciniatriticina) and yellow rust (P. striiformis) on wheatleaves based on hyperspectral imaging. The experimentwas conducted at the leaf scale under controlled laboratoryconditions. A reference spectrum from sporescale observationswas used. Least-squares factorization was applied onhyperspectral images to unveil the presence of the spectralsignal of rust spores in mixed spectra on wheat leaves. Forthe first time, this study shows an interpretable decompositionof the spectral reflectance mixture during patho-genesis.Disease severity assessmentQuantitative diagnosis of plant disease severity is one ofthe main directions of hyperspectral disease analysis. Theevaluation criteria for plant disease severity are often thedisease index and incidence. In addition, according to thepathogens and symptoms they caused, the pigment content,water content, and even structural parameters are oftenregarded as indirect evaluation criteriaZhao Y.-R. et al., 2016 used hyperspectral imaging to determinethe spatial distribution of chlorophyll and carotenoid contents in cucumber leaves infected with angular spot. Thepigment content was measured by biochemical analyzes.Partial least square regression (PLSR) models were usedto develop quantitative analysis of the relationship betweenthe disease severity, the spectra and the pigment contents.In addition, regression coefficients in PLSR models wereemployed to select important wavelengths for modeling.Finally, chlorophyll and carotenoid distributions in cucumberleaves with the angular spot infection were mapped byapplying the optimal models pixel-wise to the hyperspectralimages.Zhang J. et al., 2012 detected wheat powdery mildewdisease severity via spectral measurement and analysis. Inthis study, hyperspectral reflectances of normal and powderymildew infected leaves were measured with a spectroradiometerin a laboratory. The severity of the diseasewas determined on a nine-point scale of the disease index.A total of 32 spectral features were extracted from the labspectra and examined through a correlation analysis and anindependent t-test associated with the disease severity. Tworegression models: multivariate linear regression (MLR) andpartial least square regression (PLSR) were developed forestimating the disease severity of powdery mildew. Based onthe cross-validation result, seven spectral indices minimizingthe relative root mean square error were selected. The PLSRmodel outperformed the MLR model, with a relative rootmean square error of 0.23 and a coefficient of determinationof 0.80 when using seven indicesAssessment of genotypes resistanceAnalysis of the pathogen-host interaction makes it possibleto determine the resistance of genotypes to a specificdisease and is an important part of breeding. In breedingpractice, phenotyping of plant genotypes is carried out bymeans of labor-intensive and expensive visual assessment.In this context, hyperspectral analysis is a promising noninvasivemethod for speeding up and automating traditionalphenotyping methodsLeucker et al., 2016 evaluated the resistance of 5 differentsugar beet genotypes to Cercospora leaf spot in their study.The experiment was carried out under controlled laboratoryconditions. Lesions of Cercospora leaf spot were rated byclassical quantitative and qualitative methods in combinationwith non-invasive hyperspectral imaging. It was foundthat the spectral characteristics of the affected leaf areasdepend on the density of pathogen spores on the surfaceand on their spatial distribution. Accordingly, the number ofconidia per diseased leaf area on resistant plant was lower.The assessment of lesion phenotypes by hyperspectralimaging with regard to sporulation may be an appropriatemethod for identifying subtle differences of genotypes indisease resistance.Kuska et al., 2015 used a hyperspectral microscope todetermine the resistance of barley cultivars to powderymildew (Blumeria graminis). The reflection of inoculatedand non-inoculated leaves was recorded daily with a hyperspectrallinescanner in the visual (400\u2013700 nm) and nearinfrared (700\u20131000 nm) range 3 to 14 days after inoculation.The susceptible genotypes showed an increase in reflectancein the visible range according to symptom development.However, the spectral signature of the resistant genotype didnot show significant changes over the experimental period.Problems and prospectsof using hyperspectral technologiesfor the diagnosis of plant diseasesDespite the encouraging progress in monitoring plantdiseases based on hyperspectral technologies made overthe past few decades, some technical problems remainunresolved that make these methods difficult to apply inpractice. Studies seeking solutions to these challenges willshape future trendsCurrently, low-altitude, airborne and satellite multispectralsystems are widely used in agricultural production tomonitor the canopy based on vegetation indices . But reliable remotesensing monitoring of plant diseases and pests is usuallyachieved when symptoms are fully exhibited, which maybe too late for guiding the prevention. Despite significantresults in scientific research on the use of hyperspectralsensors for early detection of plant diseases, their practicalapplication in field and greenhouse conditions in precisionfarming systems is still an unresolved problem.Most of these studies have been conducted in controlledconditions, often utilizing artificial illumination and preciselyregulating the directions of incoming light and reflectedlight being registered by positioning the camera or sensorat a defined angle toward the leaf tissue. The illuminationconditions in the field are very different from laboratoryones, which creates enormous difficulties for reliably quantifyingdiseases in a natural canopy. Canopy regions locatedin sunlight appear much brighter than canopy layers situatedin the shade. Tissue color depends on the angle of the tissuetoward both the incoming sunlight and the reflected outgoinglight. Heterogeneities in image brightness change fromminute to minute. Therefore, setting a threshold for distinguishingbetween healthy and diseased tissue would meantaking the overall brightness of the specific image within thelocation into account, as well as the angle of incidence oflight, which is currently a matter of intense research .Another unsolved problem is to accurately detect a specificdisease under realistic field conditions where severalcrop stressors may occur simultaneously. Currently, mostmonitoring studies or applications are conducted in experimentalfields or areas with prior information about the type ofpathogen. For an area that lacks corresponding information,it is challenging to achieve a reliable and accurate monitoringresult. Many pathogens, as well as abiotic stressors, havesimilar symptoms and, therefore, a similar spectral signature.Some state-of-the-art algorithms, such as deep learning algorithms,may play an important role in differentiating biotic and abiotic stressors in field and greenhouse conditions . Besides, it is necessaryto promote the establishment of a knowledge base with thebackground information about diseases .The prior information may lower uncertainty in themonitoring of plant diseasesPlant diseases are causing significant economic losses in theagricultural production around the world, especially giventhe climate change that has taken place in recent years.A promising technology for a non-invasive, fast, efficientand reliable way to detect and identify plant diseases is theuse of hyperspectral sensors and platformsNew technologies are expanding human perception byproviding information beyond the visible spectrum. Theanalysis of the reflection spectrum of plant tissue makes itpossible to classify healthy and diseased plants, assess theseverity of the disease, differentiate the types of pathogens,and identify the symptoms of biotic stresses at early stages,including during the incubation period, when the symptomsare not visible to the human eyeDue to the huge amount of information, the most promisingmethods for processing hyperspectral data are machinelearning and neural networks. Currently, hyperspectralmethods for diagnosing plant diseases are still at an earlystage of development. In addition to its being an expensivetechnology, many technical difficulties limit its applicationin production. However, with advances in sensor technologyand data analysis techniques, hyperspectral imaging can beexpected to become one of the important tools for studyingplant diseases.The authors declare no conflict of interest.Aasen H., Burkhart A., Bolten A., Bareth G. 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A review ofadvanced technologies and development for hyperspectral-basedplant disease detection in the past three decades. Remote Sens.2020;12:3188. DOI 10.3390/rs12193188Zhao Y.-R., Li X., Yu K.-Q., Cheng F., He Y. Hyperspectral imagingfor determining pigment contents in cucumber leaves in responseto angular leaf spot disease. Sci. Rep. 2016;6:27790. DOI10.1038/srep27790.Zheng C., Abd-Elrahman A., Whitaker V. Remote sensing and machinelearning in crop phenotyping and management, with an emphasison applications in strawberry farming. Remote Sens. 2021;13:531. DOI 10.3390/rs13030531.Zhou R.-Q., Jin J.-J., Li Q.-M., Su Z.-Z., Yu X.-J., Tang Y., Luo S.- M.,He Y., Li X.-L. Early detection of Magnaporthe oryzae-infectedbarley leaves and lesion visualization based on hyperspectralimaging.Front. Plant Sci. 2019;9:1962. DOI 10.3389/fpls.2018.01962."} +{"text": "This article has been corrected: The COI statement has been updated. Please see the revised text below:W.S.E-D. is a co-founder and shareholder of Oncoceutics, Inc. W.S.E-D. is fully compliant with institutional disclosure requirements and conflict of interest rules. Dr. Michael Andreeff is also a shareholder of Oncoceutics, Inc. Some of the additional authors are employees or shareholders at Oncoceutics, Inc.74380-74392. https://doi.org/10.18632/oncotarget.11814Original article: Oncotarget. 2016; 7:74380\u201374392."} +{"text": "In the published version of this article, a grant number was omitted from the section \u2018Funding Information\u2019. The section should have read:This work was funded by an MRC grant (MR/S001026/1) to M. H., while S. C. was funded by the China Scholarship Council. G. R. F. C., C. B. and P. R. were funded by FAPESP .The authors apologise for any inconvenience caused."} +{"text": "The availability of targeted therapies has transformed the management of advanced NSCLC; however, most patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored.We performed a prospective cohort study of patients with suspected advanced lung cancer on the basis of cross-sectional imaging results. Blood from the time of biopsy was sequenced using a commercially available 74-gene panel. The primary outcome measure was time to first-line systemic treatment compared with a retrospective cohort of consecutive patients with advanced NSCLC with reflex tissue NGS.KRAS [five KRAS G12C], 13 EGFR, two ERRB2, two MET, one BRAF, one RET). The NGS results were available before the first oncology visit in 85% of cohort 1 versus 9% in cohort 2 (p < 0.0001), with more cohort 1 patients receiving a guideline-concordant treatment recommendation at this visit . Time-to-treatment was significantly shorter in cohort 1 compared with cohort 2 , with a shorter time-to-treatment in patients with specific driver mutations .We analyzed the NGS results from 110 patients with newly diagnosed advanced NSCLC: cohorts 1 and 2 included 55 patients each and were well balanced regarding baseline demographics. In cohort 1, plasma NGS identified therapeutically informative driver mutations in 32 patients (58%) (13 Plasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with usual care. Before this visit, patients have typically undergone an extended workup beginning with identification of a radiographic abnormality and subsequent subspecialty referral for biopsy and confirmation of lung cancer followed by referral to medical oncology and other cancer specialists. This process may take several weeks. The timeliness of biomarker testing is essential to avoid treatment delays or inappropriate treatment assignments if therapeutic decisions are made before availability of results.This single-center, prospective cohort study was conducted at the University of Pennsylvania between September 2019 and April 2021. Eligible patients had suspected advanced (stage IIIB-IV) NSCLC by imaging and underwent evaluation by an interventional pulmonologist for diagnostic biopsy. Patients with other active malignancies were excluded. Blood was collected before the time of diagnostic biopsy and sequenced using the Guardant360 74-gene next-generation sequencing (NGS) assay.A contemporary historical cohort of consecutive patients with advanced NSCLC that underwent conventional reflex tissue NGS was identified in the 12 months before prospective enrollment (September 2018\u2013August 2019) (cohort 2). Patients in the historical cohort were each evaluated by an interventional pulmonologist, underwent biopsy confirmation of advanced NSCLC with reflex tissue NGS, and received oncologic care at our center. The study was approved by the institutional review board, and all prospectively enrolled patients provided written informed consent. All statistical analyses were two-sided and performed using Stata version 15.1 .p\u00a0= 0.84, Pearson\u2019s chi-square; A total of 65 patients with suspected advanced NSCLC were prospectively enrolled and completed plasma NGS at the time of biopsy. After excluding patients without NSCLC (n\u00a0= 10), 55 patients with advanced NSCLC were included in the final analysis (cohort 1). Cohort 2 included 55 consecutive patients with advanced NSCLC who received SOC reflex tissue genotyping . The cohKRAS [five G12C], 13 EGFR, two ERRB2 [HER2], two MET, one BRAF, and one RET) . Plasma p\u00a0= 0.32, Mann-Whitney). NGS results were available before the first medical oncology visit more frequently in cohort 1 . For patients with nonsquamous NSCLC, reflex tissue NGS was completed for 85% of patients in both cohorts, with 15% of patients having insufficient quantity or quality of tissue DNA for NGS. Turnaround time for plasma NGS was shorter compared with tissue . Among the 46 patients in cohort 1 with nonsquamous NSCLC evaluated by a medical oncologist, a higher percentage of patients received specific treatment recommendations at the first visit compared with the 54 patients in cohort 2 . In these patients, the median time-to-treatment was shorter in cohort 1 compared with cohort 2 , with an even shorter time-to-treatment when limited to patients identified to have a specific driver mutation .The median time (interquartile range [IQR]) from diagnostic biopsy to first medical oncology visit was similar between cohorts . Although rapid on-site cytology was not used in this study, the use of this practice to confirm a nonsmall cell histology before sending plasma for sequencing may reduce the number of tests that are unlikely to inform clinical decision-making. Finally, although this approach is patient centered, which could alleviate anxiety of awaiting genomic results and reducing treatment delays, the cost of performing parallel sequencing of plasma and tissue warrants further investigation.Our results reveal that plasma-based sequencing performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with reflex tissue genotyping. Further prospective studies are warranted to validate these findings and determine whether this approach is associated with improved patient outcomes and satisfaction.Jeffrey C. Thompson, C. Aggarwal, E. Carpenter: Conceptualization, Methodology.Jeffrey C. Thompson, C. Aggarwal, J. Wong, M. Andronov, D. M. Dibardino, C. T. Hutchinson, K. C. Ma, A. Lanfranco, E. Moon, A. R. Haas, A. P. Singh, C. A. Ciunci, M. Marmarelis, C. D\u2019Avella, J. V. Cohen, J. M. Bauml, R. B. Cohen, C. J. Langer: Investigation.Jeffrey C. Thompson, C. Aggarwal, E. Carpenter, J. Wong, V. Nimgaonkar, M. Andronov, W. Hwang: Data curation.Jeffrey C. Thompson, C. Aggarwal, E. Carpenter, J. Wong, V. Nimgaonkar, A. Vachani, W. Hwang: Formal Analysis.Jeffrey C. Thompson, C. Aggarwal, J. Wong, V. Nimgaonkar, W. Hwang, M. Andronov, D.M. Dibardino, C. T. Hutchinson, K. C. Ma, A. Lanfranco, E. Moon, A. R. Haas, A. P. Singh, C. A. Ciunci, M.\u00a0Marmarelis, C. D\u2019Avella, J.V. Cohen, J. M. Bauml,\u00a0R.\u00a0B. Cohen, C. J. Langer, A. Vachani, E. L. Carpenter: Manuscript writing, Final approval of manuscript."} +{"text": "Dear Editor,MicroRNAs (miRs) have emerged as cardiovascular biomarkers and myocardial regulators with diagnostic and therapeutic potential.Materials and Methods).Here a multi\u2010step strategy provided evidence of differentially expressed miRs (DEmiRs) in plasma and myocardial tissue from HCM by next generation sequencing (NGS). Principal component analysis of NGS data did not clearly define a separation between HCM and CTRL,\u00a0while a significant differential expression was found in a subset of 139 plasma miRs. Twenty\u2010eight of them were DEmiRs significant both for p value and false discovery rate were determined in septal myectomy samples from 21 obstructive HCM of our cohort and nine donor hearts (ctrl). RT\u2010qPCR showed three downregulated with significant linear fits Figure S.n silico analysis of myocardial DEmiRs and of miRs associated with clinical parameters predicted networks of targets genes and interacting proteins was also found in HCM samples. PTEN deletion in mice drove variable in vivo and in vitro effects on cardiomyocyte hypertrophy,I Figures\u00a0, and S8DIn summary Figure\u00a0, startinConceptualization: C.F. and P.G.C.; Data curation: D.L., G.B, I.O. and O.R.; Formal analysis: M.R. and C.F.; Investigation: M.L., D.L., G.B., G.d'A., G.B, F.deC. and C.F.; Methodology: M.L., D.L.; Project administration: C.F.; Supervision: P.G.C.; Visualization,: M.L., M.R. and C.F.; Writing original draft: M.L., D.L., C.F. and P.G.C.; Writing review & editing: I.O., C.F. and P.G.C. All authors have read and agreed to the published version of the manuscript.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-021-91501-y, published online 07 June 2021Correction to: The original version of this Article contained errors.Christopher V. Suschek was incorrectly listed as an author of the original Article, and has subsequently been removed.The Author Contributions section now reads:V.G. wrote the manuscript, designed and directed the study. N.S. carried out the most experiments. L.O. and J.G. contributed to the sample preparations. J.W. supervised the project. J.G. had substantively revised the manuscript and has helped to interpret the data. All authors provided critical feedback and helped shape the research and manuscript.In addition, Figure 1 did not display correctly. The original Figure\u00a0The original Article and accompanying Supplementary Information files have been corrected."} +{"text": "Progress in genome sequencing, assembly and analysis allows for a deeper study of agricultural plants\u2019chromosome structures, gene identification and annotation. The published genomes of agricultural plants provedto be a valuable tool for studing gene functions and for marker-assisted and genomic selection. However, largestructural genome changes, including gene copy number variations (CNVs) and gene presence/absence variations(PAVs), prevail in crops. These genomic variations play an important role in the functional set of genes and the genecomposition in individuals of the same species and provide the genetic determination of the agronomically important crops properties. A high degree of genomic variation observed indicates that single reference genomes do notrepresent the diversity within a species, leading to the pangenome concept. The pangenome represents information about all genes in a taxon: those that are common to all taxon members and those that are variable and arepartially or completely specific for particular individuals. Pangenome sequencing and analysis technologies provide a large-scale study of genomic variation and resources for an evolutionary research, functional genomics andcrop breeding. This review provides an analysis of agricultural plants\u2019 pangenome studies. Pangenome structuralfeatures, methods and programs for bioinformatic analysis of pangenomic data are described The genome sequence is the basis for a chromosome structurestudying, a distribution of repetitive and coding sequences, andgenes identification and annotation . Thedifferent species genomes information allows a comparativephylogenetic analysis to study relationships among species,their origins, and evolutionary features . In agricultural plants, all these allows toassess the impact of a genetic variability on a gene function,to identify the genes responsible for the most valuable traitsin crops .A single organism chromosome sequences serve as the basis(\u201creference\u201d genome) for studying other genomes of the samespecies. The number of sequenced, assembled and annotatedplant reference genomes increases every year . The Ensembl Plants database version 48 (September2020) contains 93 assembled and annotated plant genomes. Based on the reference genome sequencing and the sequencing of the same species representativesgenomes , geneticvariability analysis, the study of the genome single-nucleotidepolymorphisms (SNPs) and large structural variants (SVs) areperformed. The large structural variants are the most difficultto identify using a short-read sequencing, but due to the thirdgeneration sequencing technologies , the SVsidentification is becoming more accessible and reliable. Thereis a growing evidence that structural variations, including copynumber variations (CNVs) and presence/absence variations(PAVs), are prevalent in crops and lead to significant variations in gene content between individuals of the same species. For a more efficient analysis and description of the geneticdiversity, the concept of \u201cpangenome\u201d was proposed . The pangenome represents the information aboutthe complete set of genes in a biological cluster (taxon), suchas species, among which one can distinguish a set of universal(core) genes that are common to all organisms, and a set ofunique (variable) genes that are partially shared or individually specific . Until recently pangenomestudies have been focused on finding genes presence or absence in organisms to determine the universal or unique setof genes.The concept of the \u201cpangenome\u201d was proposed in for the Streptococcus agalactiae bacterial species.To date, there are several definitions of this term, wich arebased on two main concepts: a function based and a structurebased . The structural conceptconsiders the pangenome as complete set of taxon genomicsequences. Within this concept, taxon members genomic sequences (of the same species or genus) are compared with eachother and on this basis their common unique (non-redundant)set of DNA fragments of the same length is determined. These sequencesdescribe the structure of the pangenome .The second pangenome concept is based on its functionalrepresentation. In this case, the pangenome can be describedas a set of all genes for particular taxon representatives . However, for a large number of relatedorganisms, such a set is degenerate, because they contain alarge number of genes with a high level of similarity in primary structure, and, consequently, in function. Pangenomeredundancy can be eliminated by combining similar genesequences into functional families . In thiscase, the representative genes of the same functional family indifferent organisms are considered as one sequence in termsof function.The set of organisms in pangenome analysis usually limitedto a single species. However, some authors use a broader interpretation of the pangenome. For example, V.V. Tetz (2003)considers the pangenome as a complete genes set of all livingorganisms, viruses and mobile elements.Pangenome genes can be divided into two groups accordingto their occurence in different organisms .The first group includes genes that are found in all membersof the taxon. This group of genes is called the universal setor core gene set. The second group of genes includes genesthat occur in a part of the taxon. This genes group is calledindispensable, accessory or variable genes. Among the second genes group, the unique genes that are present only inthe single individual are of particular interest. Universal andvariable genes represent the functional core and the diversityof species members, respectivelyFrom an evolutionary perspective, universal genes aremostly responsible for vital functions and they tend to beconserved within a species. In contrast, variable genes andtheir specific part, unique genes, contribute to the diversityof the species, enabling them to adapt to different environmental conditions. The proportion of unique genes in thestudied crops pangenomes ranges from 8 to 61 % . However, the resulting size of the unique genomeis likely to be underestimated due to the inability of currentstrategies and technologies to detect all functional changesin geneshttps://pangp.zhaopage.com. Thereby, the organismssample sizes significantly affects the pangenome size estimation and the universal gene proportion in it.Based on the sequence of one genome it is impossible todetermine, which genes are common to all species members.However, each new sequence can be assigned to a universalor variable part of the pangenome. The more taxon genomesare sequenced, the more unique genes are found. This resultsto a pangenome size increasing with an increase in the genomes number. However, for a universal genes set, increasinggenomes number leads to the opposite result: some universalgenes may be absent in other species members. As a result, thepangenome size \u2013 the set of all the different species genes \u2013increases, while the estimated size of the universal genes settends to decrease . Thisrelation is shown schematically in Fig. 1. Each point on thegraph corresponds to an estimate of the genes number in thepangenome for a set of k genomes (taken randomly from thefull sample of N genomes under study). With k increasing, theestimate of the total pangenome genes number increases (red line), and the unique genes number decreases (blue dashedline). Examples of dependencies for real pangenomes can befound at In addition to the sequenced genomes number, the pangenome unique gene size and proportion is also influenced bymany factors. The choice of a sample for analysis is one ofthem: (1) wild and cultivated species together will give a largerpangenome with a higher percentage of unique genes thanonly cultivated plants ; (2) the ploidy level, mode of reproduction, bottlenecksduring domestications, etc. A plant species with higher levelsof ploidy and outbreeding and reduced diversity because ofdomestication tend to have a higher percentage of uniquegenes .It can be assumed that the addition of an unlimited numberof new genomes to the pangenome could lead to its unlimitedgrowth. However, the gene diversity studies in crop specieshave shown the number of unique genes decrease as thenumber of sequenced samples increases. This suggests that,given a certain number of taxon representatives, the inclusion of additional genomes in the pangenome will no lead toa further increase in its genes number. Such pangenomes arecalled \u201cclosed\u201d. The \u201cclosed\u201d pangenome was found in tomato, corn , rice , soybeans , sunflower , Brachypodium distachyon ,Brassica napus and Brassica oleracea. However, there are also \u201copen\u201d pangenomes, in which thetotal genes number grows with each new sample added. Openpangenomes are specific for microorganisms, for examplefor the wheat leaves septoria fungal pathogen Zymoseptoriatritici . The bacterium Paenibacilluspolymyxa pangenome also belongs to the open type .If organisms from the population are randomly selected,the pangenom type can be estimated by plotting the numberof found genes in each new genomic sequence . Thepangenome genes number reaching a plateau after analysisof certain genomic sequences number characterizes \u201cclosed\u201dpangenomes . The \u201copen\u201d pangenomes are characterized by a constant increase in size whennew genomes are added .1. The data obtained demonstrates thenumber of samples for pangenome analysis varies from three(B. rapa) to three thousand (Oryza sativa). The genes numberin pangenomes varies from 35 thousand in diploid rice to128 thousand in hexaploid bread wheat. The proportion ofuniversal genes ranged from 41 % in \u041cedicago truncatulato 84 % in B. rapa.The comparison of the pangenome size and the universaland variable pangenome parts for some plant species is shownin (Supplimentary 1)1 Supplementary materials 1\u20133 are available in the online version of the paper: http://www.bionet.nsc.ru/vogis/download/pict-2021-25/appx2.pdfResearches show that universal genes are responsible forfundamental cellular processes, while variable genes are associated primarily with functions that can give an advantagein different environmental conditions. Thus, Brachypodiumdistachyon pangenome analysis demonstrated universal geneset annotations are enriched with terms such as \u201cglycolysis\u201d,\u201csteroid\u201d, \u201cglycosylation\u201d, \u201cco-enzyme\u201d .Variable genes sets annotations were most of all enrichedwith terms \u201cprotective function\u201d, \u201cdevelopment\u201d. In the samework, it was shown the nonsynonymous/synonymous substitution rate ratio in variable genes are higher than in universalgenes. In addition, the universal genes orthologs in rice andsorghum were found to be more conservative than orthologsof the variable genes set. Universal genes expression level isgenerally higher than variable genes .Similar results were obtained in the soybeans , cabbage , and wheat pangenomes analysis.The analysis of several agricultural plant pangenomesshowed that (1) the variable genes sequences are more mutable than universal genes; (2) the nonsynonymous substitution rate ratio is higher in variable genes;(3) variable genes are characterized by a wide function diversity; (4) the variable and universal genes functional characteristics are different, the variable genes are more related tothe response to environmental factors, receptor activity and signal transduction, the universal genes are more related tobasic cellular functions. Thus, the universal genes representthe conservative core of the pangenome , while the variable genes represent its mutable part(both in terms of function and in terms of primary structureand expression patterns). The transcriptome analysis is another gene set analysing method in several members of a taxon. The transcript nucleotidesequences (mainly mRNA), their expression levels estimationand the isoforms presence can be obtained by high-throughputsequencing (RNA-seq), which is significantly cheaper than thegenome sequencing. Transcriptomic data allows estimatinggenes presence in the genome only if they are expressed in aplant tissue or organ. Thus, a set of transcripts cannot represent the full genome gene composition, but it is possible toobtain an approximate estimation . In this case, the transcriptome assembly requiressignificantly less computational resources, and the currentmethods allow obtaining it with high qualityA study of the 503 inbred maize lines pantranscriptomerevealed genetic diversity in protein-coding genes: morethan 1.5 million single-nucleotide variations were found,and mutations associated with plant development traits were identified . M. Jin et al. (2016) also analysed the 368 inbred maizelines pantranscriptome. The analysis identified more thantwo thousand sequences that were not represented in themaize reference genome, including genes responsible for thebiotic stress response. Variations that are associated with thegene expression level (eQTL) were analysed. The analysis\u2019results were projected to metabolic networks, which allowedto specify their functioning mechanisms.Y. Ma et al. (2019) analysed 288 barley transcriptomesequencing experiments. Among the collected transcripts,about 30 % showed no similarity to the reference genome. Theresults of the pantranscriptome analysis revealed that pathogenresistance genes are more numerous in wild-grown barley, andsuch genes were subjected to greater selection pressure duringdomestication compared to genes in other species.The pangenome bioinformatic analysis can be divided intothe following main steps: The pangenome sequence assembling. The conserved and variable genomic sequences regionsidentification. Genes identification/prediction and functional annotation. Polymorphisms identification. Storage, rapid access and visualization of the pangenomicdata.The following pangenome assembly strategies exist: assembly-alignment; metagenome approach; mapping-assembly.Assembly-then-map. This strategy consists of each taxonseparately de novo assembly, followed by sequences alignment with each other as well as with the reference genome todecrease redundancy and identify a set of common and variable sequence regions. Several software packages have beendeveloped for the genome assembly: Velvet , SOAPdenovo , ALLPATHS and MaSuRCA . This approachis time-consuming and computationally intensive. The de novoassembly strategy has been used for the pangenome analysisof cultivated soybean , wild soybean , rice , B. oleracea and Medicago truncatula .Metagenomic-like approach. This strategy consists toall sequenced fragments from different taxon representatives combining into one pool and the de novo assemblingpangenome sequences from these fragments. Each assembledcontig is then assigned to a particular genome by the sampleoriginal reads alignment to the metagenomic assembly andthen contig coverage is evaluated. This method allows lowcoverage sequencing results to be handled. The metagenomicapproach has been used to analyse the genome of rice and tomato .Map-then-assembly. This strategy uses one completegenome assembly (reference sequence) as the basis for the genome assembly of the other taxon members (guide assembly).The reads from a single species are mapped to the referencegenome, and not mapped reads are discarded and assembledseparately. The reference genome sequence is complementedwith new sequences, and the samples are compared with thereference genome. This method reduces the time requiredto construct a pangenome. If a genomic segment is found inmore than one sample, the segment will be integrated fromthe first sample while the de novo method creates two complete genomes. This strategy has been used in the sunflowerpangenome analysis .It should also be noted, that in a number of studies, theresearchers did not use the genomic sequences assembly, butaligned short reads to a reference genome. This approach allows assessing the SNP and phenotypic plants characteristicsrelations. Methods based on the short reads alignment arealso described, which allows the identification of structuralrearrangements, duplications and gene losses . The alignment method was used in the maize pantranscriptome analysis , in the assessment ofCNV\u2019s changes in the potato pangenome analysis .Based on a comparison of sequences, genome annotationallows identifying gene sequences in taxon representatives\u2019genomes, to determine orthologous genes and universal andvariable genes families. Several software packages are designed for pangenomes automatic annotation. They performthe main steps of the pangenome sequence analysis and annotation. The capabilities of a number of these programs arebriefly described below.PGAP performs large-scale genesearch, functional annotation, orthologous gene clusters ontology term enrichment, species evolution analysis, pangenomestructural analysis, and the universal and variable pangenomeparts identification. In the updated version of this program,PGAP-X , methods for presentationand visualization of pangenome analysis results are furtherdeveloped.PpsPCP was developed fora pangenome PAV identification. The analysis is based on afull-genome taxon and a reference genome sequences comparison in several rounds with sequential correction of bothgene set and gene alignment sites in the reference genome.As a result, a pangenome gene set is created by combiningthe individual genome sequences with the reference genomeand their annotation.BPGA provides a wide range ofpangenome analysis opportunities: gene clustering based onsequence similarity, orthologs presence/absence analysis, thepangenome and its universal part sizes plotting, phylogenetictree reconstruction, metabolic pathway and functional annotation analysis, GC composition deviation assessment, variousstatistical pangenome characteristics calculation, and severalother features.panX aims to identify orthologous genesclusters. The sequence comparison clustering, verification andrefinement of cluster composition based on evolutionary distance analysis and phylogenetic reconstruction, and assessesthe association between the gene composition of individualtaxon members and their phenotypes are used.Pan4Draft is designed to improvepangenome annotation by adding sequence information onunfinished genomes. An annotation and assembly to thechromosome level in these genomes is incomplete, but theirsequences contain genomic DNA fragments and providevaluable information about the species genome diversity.Information about plant pangenome analysis methods andsoftware for processing and analysis of plant pangenome areprovided in Supplementary 2 and 3.Currently, the research field of the crop pangenomes sequencing and analysis is developed rapidly and provides more andmore information about genetic variations and new genes. One of the fundamental problems in the crop pangenomesstudy is to evaluate the genetic diversity of their cultivatedrepresentatives as well as wild relatives. This analysis allowsus to establish the origin and evolution of cultivated plants, toestimate the breeding process impact on the genetic structureof varieties. Thus, the pangenome analysis helps to answer anumber of important questions about patterns of the genomeevolution at species level, about mechanisms of the genesde novo origination, the gene functions diversity and theirassociations with phenotypic traits of plants.One of the important directions of the crop pangenomeresearch is the wild relatives\u2019 genome sequencing and analysis. It is supposed that wild relatives of cultivated plants maycontain a pool of genes related to adaptation of organisms to environmental conditions, response to biotic stresses; i. e.those genes that may have been lost by cultivated plants asa result of artificial selection (bottleneck effect) .The discovered genes can be further used to create new genotypes that are more resistant to pathogens, pests and abioticstress. Thus, the study of agricultural plant pangenomes hasnot only a fundamental aspect, but is also important in termsof practical breedingA better understanding of genetic diversity, combined withadvanced sequencing technologies and high-throughput phenotyping can facilitate trait analysis to identify useful geneticmutations. In addition, it allows to access a wider range ofgenetic resources helps to select the best strategies in breeding programmes and ultimately accelerates crop breeding todevelop varieties with consistently high yields under stressfulconditions.Pangenomic studies offer a wider understanding of the cropgene pools genetic diversity than genome resequencing studiesand thus can be extremely useful for the crop improvement.Nevertheless, the knowledge obtained through pangenomicresearches requires integration with QTL/GWAS and genomeresequencing studies to identify important genes and allelesto be used in an effective breeding strategy.The authors declare no conflict of interest.Alcaraz L.D., Moreno-Hagelsieb G., Eguiarte L.E., Souza V., HerreraEstrella L., Olmedo G. Understanding the evolutionary relationshipsand major traits of Bacillus through comparative genomics. BMCGenomics. 2010;11(1):332.Bragina M.K., Afonnikov D.A., Salina E.A. Progress in plant genomesequencing: research directions. 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DOI 10.1007/s00122-013-2177-7."} +{"text": "Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea.Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage.Using a combination of Illumina short\u2010read, 10X Genomics linked\u2010read, and Hi\u2010C sequencing data, our 1.005 Gb B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.This study provides the first genome assembly for the snail With >240 million people worldwide estimated to require treatment, the World Health Organization considers schistosomiasis to be the second most prevalent parasitic disease after malaria . As suchSchistosoma mansoni (NCBI:txid6183) in humans results when cercariae emerge into the water from their freshwater snail intermediate hosts in the genus Biomphalaria, and seek out and penetrate submerged body parts through the skin. Once inside the human body, adult worms lay eggs, which are deposited in the blood venules and will cross the intestinal wall to leave the body in the faeces. In addition, eggs that fail to cross the intestinal wall (named \u201creflux eggs\u201d) circulate to the liver where they grow, emerge, and cause disease. Miracidia larvae hatch from eggs that reach water, then seek out and penetrate a new snail intermediate host. Following this, sporocysts develop in the infected snails, and subsequently free-living cercariae emerge from the snail into the water, completing the parasitic life cycle. Among the 34 described species of Biomphalaria snails, 18 species have been demonstrated to be potential vectors for S. mansoni. Different geographical locations are dominated by different species of Biomphalaria.Infection by Biomphalaria snails is South America and Africa wi wiM. honv0.9.24) with parme reads . Gene moRRID:SCR_012954) . T. TB. glaplicates .B. straminea and 12 other animal proteomes were inferred using OrthoFinder v. 2.5.2 [k), and k = 1 showed the best likelihood.Orthologues and orthogroups in _017118) with def_017118) . Orthogr_017118) from theRRID:SCR_002456) [Orthogroups were assigned Gene Ontology (GO), EuKaryotic Orthologous Groups (KOG), KEGG, and KEGG Orthology (KO) terms by inheriting the terms from genes found within the groups. The functional term annotations were performed using eggNOG . Functio_002456) under th_002456) . Signifi_002456) , and \u201cpa_002456) .B. straminea and 12 other animals with chromosome-level or near chromosome-level assemblies were used in macrosynteny analysis. Oxford synteny plots were generated following previously described methods [Single-copy orthologues anchored by mutual best Diamond blastp v0.9.14.115 hits (\u2013e methods using th\u20136\u00a0or 10\u20138 M\u00a0of methyl farnesoate (MF) (Sigma), 6 \u00d7 10\u20135 M\u00a0of\u00a0simvastatin (Sigma), or 10\u20136 M\u00a0of 20-hydroxyecdysone in separate set-ups. The chemicals were first dissolved in acetone and diluted to the target concentration in the treatment container. The control set-up contained the same number of individuals and was treated with the same concentration of acetone in corresponding experiments. Each replicate of snails was exposed for 24 hours to these treatments without any feeding. Post-treated animals were rinsed with double-distilled water and shells were removed prior to whole-body total RNA extraction. The RNA from each experiment was isolated using TRIzol reagent following the manufacturer's protocol. Purified RNA was dissolved in nuclease-free water. The complementary DNA (cDNA) synthesis was performed using the iScript gDNA Clear cDNA Synthesis Kit (BioRad) following the manufacturer's protocol. The cDNA was used in subsequent quantitative real-time PCR. The amplification conditions were as follows: initial denaturation at 95\u00b0C for 30 s, followed by 40 cycles of 95\u00b0C denaturation for 15 s,\u00a057\u00b0C\u00a0primer annealing for 15 s,\u00a0and 72\u00b0C extension for 15 s.\u00a0Primer\u00a0details are listed in B. straminea cDNA prior to experiments to ensure their specificity. Each sample was analysed in replicates. The expression of each target gene transcript was normalized to the housekeeping gene, myoglobin (Myo), as adopted in previous studies [Experimental adult animals of \u223c1 cm\u00a0with reproductive capability were isolated from the culture and were rinsed in double-distilled water to remove any contaminants. Three individuals per set were placed in a glass container, with a well of 3.5 cm\u00a0in diameter and 0.8 cm\u00a0in depth, filled with 2 mL\u00a0of double-distilled water with either 10 studies . The subThe raw genome and RNA sequencing data have been deposited in the SRA under Bioproject No. PRJNA673593. The final chromosome assembly was submitted to NCBI Assembly under accession No. JADKLZ000000000. All data can also be found in the GigaScience Database .Supplementary Information S1. Sequencing data.Supplementary Information S2. (a) Tables of homeobox gene sequences in B. straminea, B. glabrata, a synteny comparison of homeobox genes, and comparison of ParaHox gene linkage. (b) Distribution of homeoboxes in the genome of Biomphalaria glabrata. (c) Alignments and phylogenies of each class of homeobox sequences.Supplementary Information S3. Ecdysteroid genes.Supplementary Information S4. Insulin pathway genes.Supplementary Information S5. Synteny information.Supplementary Information S6. Gene expansion and contraction.Supplementary Information S7. Heat shock protein family genes.Supplementary Information S8. Cholesterol genes and primers.Supplementary Information S9. Phylogenetic trees.Supplementary Information S10. Tables.giac012_GIGA-D-21-00243_Original_SubmissionClick here for additional data file.giac012_GIGA-D-21-00243_Revision_1Click here for additional data file.giac012_GIGA-D-21-00243_Revision_2Click here for additional data file.giac012_Response_to_Reviewer_Comments_Revision_1Click here for additional data file.giac012_Reviewer_1_Report_Original_SubmissionJacob Tennessen -- 8/28/2021 ReviewedClick here for additional data file.giac012_Reviewer_2_Report_Original_SubmissionCoen Adema -- 9/5/2021 ReviewedClick here for additional data file.giac012_Reviewer_2_Report_Revision_1Coen Adema -- 1/5/2022 ReviewedClick here for additional data file.giac012_Supplemental_FilesClick here for additional data file.BLAST: Basic Local Alignment Search Tool; BUSCO: Benchmarking Universal Single-Copy Orthologs; BWA: Burrows-Wheeler Aligner; cDNA: complementary DNA; gDNA: genomic DNA; kb: kilobase pairs; KEGG: Kyoto Encyclopedia of Genes and Genomes; LINE: long interspersed nuclear element; LTR: long terminal repeat; Mb: megabase pairs; NCBI: National Center for Biotechnology Information; PASA: Program to Assemble Spliced Alignments; SINE: short interspersed nuclear element; SRA: Sequence Read Archive.The authors declare that they have no competing interests.This work was supported by the Hong Kong Research Grant Council Collaborative Research Fund(C4015-20EF), General Research Fund (14100919), NSFC/RGC Joint Research Scheme (N_CUHK401/21), and The Chinese University of Hong Kong Direct Grant . Y.Y., W.L.S., C.F.W., S.T.S.L., and Y.L. were supported by the Ph.D. studentships of The Chinese University of Hong Kong. A.H. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/N020146/1). T.B. is supported by a studentship from the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1). M.E.A.R. is supported by a Ph.D. studentship from the School of Biology and St Andrews University.The authors declare no conflict of interests.J.H.L.H., D.E.K.F., A.H., Z.W., S.X., Z.P.K., and S.S.C. conceived the study. J.H.L.H., D.E.K.F., and A.H. supervised the study. W.N., J.H., and T.S. assembled the genome. W.N. carried out the gene model prediction and comparison. Y.Y. carried out the heat shock protein analyses. Y.X. carried out the gene gain and loss and synteny analyses. W.L.S. and C.F.W. carried out the sesquiterpenoid analyses. Y.Y., W.L.S., and S.Y.L. carried out the ecdysteroid analyses. M.E.A.R. and Y.L. carried out the homeobox gene analyses. T.B. carried out the transposable element analyses. S.T.S.L. carried out the insulin analyses. W.N., Y.Y., Y.X., W.L.S., M.E.A.R., T.B., A.H., D.E.K.F., and J.H.L.H. wrote the first draft of manuscript. All authors approved the final version of the manuscript."} +{"text": "Dear Editor,Mucormycosis is a serious and rare fungal infection, which observed in a number of COVID-19 cases recently. Mucormycosis is found throughout the environment, mostly in the soil . MucormyNo ethical approval was needed.None declared.Aya Yaser Mohsen: Participated in writing the letter. Jollanar Ghanem Mohammad: Participated in writing the letter. Moatasem Hussein Al-janabi: Reviewing the letter.The authors have no conflicts of interest to declare.Not applicable.Moatasem Hussein Al-janabi.N/A.Not commissioned, externally peer reviewed."} +{"text": "The size of the nuclear genome in eukaryotes is mostly determined by mobile elements and noncodingsequences and may vary within wide limits. It can differ signif icantly both among higher-order taxa and closelyrelated species within a genus; genome size is known to be uncorrelated with organism complexity . Less is known about intraspecif ic variation of this parameter. Typically, genome size is stable within aspecies, and the known exceptions turn out be cryptic taxa. The Eisenia nordenskioldi complex encompasses severalclosely related earthworm species. They are widely distributed in the Urals, Siberia, and the Russian Far East, aswell as adjacent regions. This complex is characterized by signif icant morphological, chromosomal, ecological, andgenetic variation. The aim of our study was to estimate the nuclear genome size in several genetic lineages of theE. nordenskioldi complex using f low cytometry. The genome size in different genetic lineages differed strongly,which supports the hypothesis that they are separate species. We found two groups of lineages, with small(250\u2013500 Mbp) and large (2300\u20133500 Mbp) genomes. Moreover, different populations within one lineage alsodemonstrated variation in genome size (15\u201325 %). We compared the obtained data to phylogenetic trees basedon transcriptome data. Genome size in ancestral population was more likely to be big. It increased or decreasedindependently in different lineages, and these processes could be associated with changes in genome size and/ortransition to endogeic lifestyle. The amount of nuclear DNA in eukaryotes varies widelyand does not correlate with the complexity of an organism. This phenomenon wasdubbed the \u201cC-paradox\u201d . Patterns of genomesize variation are currently well studied both for higher-leveltaxa and for groups of closely related species from manydiverse phyla . The patterns of intraspecificdiversity are generally less known. It is generally believed thatgenome size and architecture must be common in differentpopulations so they remain genetically and reproductivelycompatible, i. e. remain a species. There are certain deviationsfrom this rule: differences between males and females due tosex chromosomes; the presence of additional B-chromosomesor large blocks of heterochromatin . However, in most cases intraspecific diversity does notexceed several percent . The known casesof high variation in intraspecific genome size are often explained bythe presence of the so-called cryptic, or sister, species, whichwere not detected earlier.The Eisenia nordenskioldi complex is a groupof species/genetic lineages of earthworms from the Lumbricidaefamily widespread in Asian Russia and also found inthe East European Plain and certain adjacent countries . This complex is knownfor its enormous morphological , karyotypic , ecological, and genetic diversity.Phylogenetic studies using genomic and transcriptomicdata confirmed deep divergence between the lineages of thiscomplex and suggestedthat it could be divided in at least two distinct species.Remarkable differences between the nuclear and mitochondrialgenomes of E. nordenskioldi genetic lineages indicatethat they diverged long ago .Significant variation in genome size not associated withpolyploidy could thus have accumulated in this complex.To elucidate this question we studied genome size in severalgenetic lineages of E. nordenskioldi using flow cytometry.Live earthworms were collected in 2020 in various locationsfrom the Urals, Siberia, and the Far East (see the Table). Thewarms were rinsed, placed individually in Petri dishes withwet paper and kept for 3\u20137 days. Genome size was estimatedaccording to the fluorescence of DAPI-stained nuclei of individualcells according to the technique of D.W. Galbraith et al. (1997). Nuclei were isolated either from several posteriorsegments of a live earthworm (100\u2013300 \u03bcg) or from the wholeanimal if it was small. A part of the material (about 50\u2013100 \u03bcg)was fixed in ethanol for DNA extraction as described below.Live material was placed in a Petri dish with 500 \u03bcl ofGalbraith buffer: 45 mM MgCl2, 20 mM 3-[N-morpholino]propanesulfonic acid (MOPS), 30 mM sodium citrate, 0.1 %Triton X-100 . Material was grinded bymultiple strokes with a razor blade. Liquid phase was transferredinto an Eppendorf tube. Another 500 \u03bcl of Galbraithbuffer was added to the Petri dish, and liquid phase was againtransferred to the Eppendorf tube. The sample was incubatedfor 15\u201360 min, filtered through a 40 \u03bcm mesh, and placed ontop of 2 ml Galbraith buffer with 3 % glycerol. The tube wascentrifuged for 10 min at 200 g; supernatant was discarded,the sediment was dissolved in 500 \u03bcl of Galbraith buffer with10 \u03bcl RNAse (1 u/\u03bcl). The sample was incubated for 30 min,mixed with 100 \u03bcl of propidium iodide (1 mg/ml) and analyzedon a FACSAria III flow cytometer .We used chicken blood cells (2C = 1250 Mbp) and mouse spleen cells (2C = 3280 Mbp) as the reference.To determine genetic lineage, we sequenced a fragment ofthe mitochondrial cytochrome oxidase I gene as described in. Phylogenetic trees built usingthe Maximum Likelihood and Bayesian inference algorithmswere taken from S.V. Shekhovtsov et al. (2020b).In this study we determined genome size for several geneticlineages of the E. nordenskioldi complex . The obtained data indicate high variation in genomesize in this complex. We could distinguish two size classes:small (250\u2013500 Mbp) and large (2350\u20133500 Mbp) genomes.Small genomes were observed in three cases, for two nonpigmentedlineages of Eisenia sp. 1 aff. E. nordenskioldi andfor the pigmented lineage 2 of this species. Large genomes(2350\u20133500 Mbp) were found in the rest of the lineages.Thus, different genetic lineages of the E. nordenskioldi havestrongly diverged genomes. This could imply that these lineagesrepresent distinct species ,or that this is the result of polyploidy in this complex. It isknown that E. nordenskioldi consists of races with differentploidy: 2n, 4n, 6n, 7n, 8n, with the chromosome number rangingfrom 36 to 142\u2013152 . Diploidchromosomeset is believed to be characteristic for the non-pigmentedpallida form . Based on this, it would be reasonable to suggest thatthe diploid non-pigmented forms are ancestral to this complex.However, transcriptomic data demonstrated that these forms are not at thebasis of the tree, and the ancestral forms were pigmented.Moreover, one of the pallida lineages had a large genomewhile one pigmented lineage had a small one. Therefore, onecannot state that all non-pigmented forms are diploid andpigmented ones are always polyploid. Moreover, the pallidaform arose independently several timesThe same arguments apply to genome size: it seems moreprobable that the ancestral genome was large. Moreover, sincethe majority of E. nordenskioldi populations are amphimictic, the ancestor of the complex was amphimictic and diploid. ForEisenia sp. 1, the tree topology also implies that large nucleargenome was the ancestral state, and some branches (lineages)subsequently went through genome compaction.Several populations from diverse geographic locations weresampled for two genetic lineages (lineages 1 and 3 of Eiseniasp. 1). Our analysis demonstrated that there is a certaingenome size diversity within these lineages, approximately 13 and 27 % for lineages 1 and 3, respectively. It is well known thatchromosome number in octaploid E. nordenskioldi populationsvaries widely, and we may suggest a similar mechanismin this case.Polyploidy results in increased body size in many animals. Earthworms, however, may not conform to thispattern: T.V. Malinina and T.S. Perel (1984) found no size differencesbetween E. nordenskioldi of different ploidy. Here wecould not measure body size, because the studied animals werecompletely or partially grinded. However, rough estimatessuggest that genetic lineages with small genomes were small oraverage in size (4\u20137 cm long), while those with large genomescould be either large (to over 10 cm for Eisenia sp. 1 lineage 3)or average (5\u201310 cm for other lineages). Therefore, althoughwe did not observe a clear pattern, we could hypothesize thatgenome size partially accounts for body size.In this study we demonstrated that nuclear genome size varieswidely among genetic lineages of the E. nordenskioldicomplex. This corroborates the remarkable differences amongthem demonstrated by molecular genetic methods. Moreover,there was also some variation between different populationsof the same lineage. Both genome expansion and contractionoccurred during the evolution of the complex.The authors declare no conflict of interest.Alvarez-Fuster A., Juan C., Petitpierre E. Genome size in Triboliumflour-beetles: inter- and intraspecific variation. Genet. Res. 1991;58:1-5. DOI 10.1017/S0016672300029542.Berman D.I., Bulakhova N.A., Meshcheryakova E.N., ShekhovtsovS.V. Cold resistance and the distribution of genetic lineages ofthe earthworm Eisenia nordenskioldi .Biol. Bull. 2019;46:430-437. DOI 10.1134/S1062359019050042.Bi\u00e9mont C. Genome size evolution: Within-species variation in genomesize. Heredity. 2008;101:297-298. DOI 10.1038/hdy.2008.80.Blakemore R.J. Earthworms newly from Mongolia . ZooKeys. 2013;285:1-21. DOI 10.3897/zookeys.285.4502.Blommaert J. Genome size evolution: towards new model systemsfor old questions. Proc. Royal Soc. B. 2020;287:20201441. DOI10.1098/rspb.2020.1441.Cavalier-Smith T. Nuclear volume control by nucleoskeletal DNA, selectionfor cell volume and cell growth rate, and the solution of theDNA C-value paradox. J. Cell Sci. 1978;34:247-278.Galbraith D.W., Harkins K.R., Maddox J.M., Ayres N.M., Sharma D.P.,Firoozabady E. Rapid flow cytometric analysis of the cell cycle inintact plant tissues. Science. 1983;220:1049-1051.Galbraith D.W., Lambert G.M., Macas J., Dolezel J. Analysis of nuclearDNA content and ploidy in higher plants. Curr. Protoc. Cytom.1997;2:6-7.Grafodatsky A.S., Perel T.S., Radzhabli S.I. Chromosome sets of twoforms of Eisenia nordenskioldi (Eisen) (Oligochaeta: Lumbricidae).Doklady Akademii Nauk SSSR = Reports of the Academy of Sciencesof USSR. 1982;262:1514-1516. (in Russian)Gregory T.R. Coincidence, coevolution, or causation? DNA content,cell size, and the C-value enigma. Biol. Rev. 2001;76:65-101. DOI10.1111/j.1469-185X.2000.tb00059.x.Gregory T.R. Genome size evolution in animals. In: The Evolution ofthe Genome. San Diego: Elsevier, 2005;3-87. DOI 10.1016/B978-012301463-4/50003-6.Hong Y., Csuzdi C. New data to the earthworm fauna of the Koreanpeninsula with redescription of Eisenia koreana (Zicsi) and remarks on the Eisenia nordenskioldi species group .Zool. Stud. 2016;55:1-15. DOI 10.6620/ZS.2016.55-12.Jeffery N.W., Hultgren K., Chak S.T.C., Gregory T.R., Rubenstein D.R.Patterns of genome size variation in snapping shrimp. Genome.2016;59:393-402. DOI 10.1139/gen-2015-0206.Kasai F., O\u2019Brien P.C.M., Ferguson-Smith M.A. Reassessment of genomesize in turtle and crocodile based on chromosome measurementby flow karyotyping: close similarity to chicken. Biol. Lett.2012;8:631-635. DOI 10.1098/rsbl.2012.0141.Malevich I.I. On the study of earthworms in the Far East. UchenyeZapiskiMGPI im. V.P. Potemkina = Transactions of the V.P. PotemkinMoscow City Pedagogical Institute. 1956;61:439-449. (in Russian)Malinina T.V., Perel T.S. Characterization of Eisenia nordenskioldi chromosome races using allozymemarkers. Doklady Akademii Nauk SSSR = Reports of the Academy ofSciences of USSR. 1984;279:1265-1269. (in Russian)Marescalchi O., Scali V., Zuccotti M. Flow-cytometric analyses of intraspecificgenome size variations in Bacillus atticus .Genome. 1998;41:629-635. DOI 10.1139/g98-064.Neiman M., Paczesniak D., Soper D.M., Baldwin A.T., Hehman G.Wide variation in ploidy level and genome size in a New Zealandfreshwater snail with coexisting sexual and asexual lineages.Evolution. 2011;65:3202-3216. DOI 10.1111/j.1558-5646.2011.01360.x.Otto S.P. The evolutionary consequences of polyploidy. Cell. 2007;131:452-462. DOI 10.1016/j.cell.2007.10.022.Perel T.S. The Range and Regularities in the Distribution of Earthwormsof the USSR Fauna. \u041coscow: Nauka Publ., 1979. (in Russian)Redi C.A., Zacharias H., Merani S., Oliveira-Miranda M., Aguilera M.,Zuccotti M., Garagna S., Capanna E. Genome sizes in Afrotheria,Xenarthra, Euarchontoglires, and Laurasiatheria. J. Hered. 2005;96:485-493. DOI 10.1093/jhered/esi080.Shekhovtsov S.V., Bazarova N.E., Berman D.I., Bulakhova N.A., GolovanovaE.V., Konyaev S.V., Krugova T.M., Lyubechanskii I.I.,Peltek S.E. DNA barcoding: How many earthworm species are therein the south of West Siberia? Russ. J. Genet. Appl. Res. 2017a;7:57-62. DOI 10.1134/S2079059717010130.Shekhovtsov S.V., Berman D.I., Bazarova N.E., Bulakhova N.A., PorcoD., Peltek S.E. Cryptic genetic lineages in Eisenia nordenskioldipallida . Eur. J. Soil Biol. 2016a;75:151-156. DOI 10.1016/j.ejsobi.2016.06.004.Shekhovtsov S.V., Berman D.I., Bulakhova N.A., Vinokurov N.N., PeltekS.E. Phylogeography of Eisenia nordenskioldi nordenskioldi from the north of Asia. Polar Biol.2018a;41:237-247. DOI 10.1007/s00300-017-2184-2.Shekhovtsov S.V., Berman D.I., Bulakhova N.A., Makarova O.L.,Peltek S.E. Phylogeography of earthworms from high latitudes ofEurasia. Acta Zool. Acad. Sci. Hungaricae. 2018b;64:369-382. DOI10 17109/AZH.64.4.369.2018.Shekhovtsov S.V., Berman D.I., Golovanova E.V., Peltek S.E. Geneticdiversity of the earthworm Eisenia nordenskioldi .Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journalof Genetics and Breeding. 2017b;21(5):588-595. DOI 10.18699/VJ17.24-o. (in Russian)Shekhovtsov S.V., Berman D.I., Peltek S.E. Phylogeography of theearthworm Eisenia nordenskioldi nordenskioldi in northeastern Eurasia. Dokl. Biol. Sci. 2015;461:85-88.DOI 10.1134/S0012496615020039.Shekhovtsov S.V., Ershov N.I., Vasiliev G.V., Peltek S.E. Transcriptomicanalysis confirms differences among nuclear genomes of crypticearthworm lineages living in sympatry. BMC Evol. Biol. 2019;19:50. DOI 10.1186/s12862-019-1370-y.Shekhovtsov S.V., Golovanova E.V., Ershov N.I., Poluboyarova T.V.,Berman D.I., Bulakhova N.A., Szederjesi T., Peltek S.E. Phylogenyof the Eisenia nordenskioldi complex based on mitochondrial genomes.Eur. J. Soil Biol. 2020a;96:103137. DOI 10.1016/j.ejsobi.2019.103137.Shekhovtsov S.V., Golovanova E.V., Peltek S.E. Cryptic diversitywithin the Nordenskiold\u2019s earthworm, Eisenia nordenskioldi subsp.nordenskioldi . Eur. J. Soil Biol. 2013;58:13-18. DOI 10.1016/j.ejsobi.2013.05.004.Shekhovtsov S.V., Golovanova E.V., Peltek S.E. Mitochondrial DNAvariation in Eisenia n. nordenskioldi (Lumbricidae) in Europe andSouthern Urals. Mitochondrial DNA A DNA Mapp. Seq. Anal.2016b;27:4643-4645. DOI 10.3109/19401736.2015.1101594.Shekhovtsov S.V., Shipova A.A., Poluboyarova T.V., Vasiliev G.V.,Golovanova E.V., Geraskina A.P., Bulakhova N.A., Szederjesi T.,Peltek S.E. Species delimitation of the Eisenia nordenskioldi complex using transcriptomic data. Front.Genet. 2020b;11:1508. DOI 10.3389/fgene.2020.598196.Shekhovtsov S.V., Sundukov Y.N., Blakemore R.J., Gongalsky K.B.,Peltek S.E. Identifying earthworms of thesouthern Kuril islands using DNA barcodes. Anim. Biodivers. Conserv.2018c;41:9-17. DOI 10.32800/abc.2018.41.0009.Stelzer C.-P., Riss S., Stadler P. Genome size evolution at the speciationlevel: The cryptic species complex Brachionus plicatilis (Rotifera).BMC Evol. Biol. 2011;11:90. DOI 10.1186/1471-2148-11-90.Thomas C.A.J. The genetic organization of chromosomes. Annu. Rev.Genet. 1971;5:237-256.Viktorov A.G. Diversity of polyploid races in the family Lumbricidae.Soil. Biol. Biochem. 1997;29:217-221. DOI 10.1016/S0038-0717(96)00086-7.Vsevolodova-Perel T.S. The Earthworms of the Russian Fauna: Cadasterand Key. Moscow: Nauka Publ., 1997. (in Russian)Vsevolodova-Perel T.S., Bulatova N.Sh. Polyploid races of earthworms in the East European Plainand Siberia. Biology Bulletin. 2008;35(4):385-388. DOI 10.1134/S1062359008040092.Vsevolodova-Perel T.S., Leirikh A.N. Distribution and ecology of theearthworm Eisenia nordenskioldi pallida dominant in southern Siberia and the Russian Far Eastern.Entomol. Rev. 2014;94(4):479-485. DOI 10.1134/S0013873814040034.Zhukov A.V., Pakhomov A.Ye., Kunach O.N. Biological Diversity ofUkraine. The Dnipropetrovsk region. Earthworms (Lumbricidae).Dnipropetrovsk, 2007. (in Ukranian)"} +{"text": "Nature Communications 10.1038/s41467-021-24602-x, published online 3 August 2021.Correction to: The original version of this Article omitted the following from the Acknowledgements:J.M.B., A.T.B., and R.G. acknowledge NSF GRFP grant no. 1444932. J.M.B. acknowledges NCI fellowship grant no. F99CA234959. A.T.B. acknowledges NCI fellowship grant no. F99CA245789. A.V.K. acknowledges NIH grant no. F31 F31CA243502. M.E.Q. acknowledges NIH grant no. F31 F31HL134241. R.L. acknowledges NIH grant no. HL082808. A.L.M. and K.S. acknowledge NIH grant no. R01GM131099. A.L.M. acknowledges NSF CAREER1832100. K.S. acknowledges NIH grant no. R01GM124472.We thank Laura Fox-Goharioon, Neil Anthony, and William Giang of the Integrated Cellular Imaging Core Facility at Emory University for maintaining and troubleshooting the SIM microscope used in this work. We also thank Eric Rentchler of the Biomedical Microscopy Core at the University of Michigan for coordinating access to software for SIM super-resolution reconstructions. We thank Rong Ma of Emory University for providing graphical illustrations. Finally, we thank Tejeshwar Rao, Reena Beggs, Tomasz Nawara, and Will Dean of the Mattheyses lab at the University of Alabama, Birmingham for helpful conversations.This has now been corrected in both the PDF and HTML versions of the Article."} +{"text": "Synchrotron Rad.28, 1284\u20131295 is corrected.A figure in the article by Baba et al.J. Synchrotron Rad.28, 1284\u20131295 is corrected.A figure in the article by Baba"} +{"text": "This au2 Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAThe updated authorship is listed as below:Emma Rodriguez, Guangsheng Pei, Zhongming Zhao, Sang T. Kim, Alexis German and Prema RobinsonThe \u201cAuthor Contributions\u201d statement thus should be updated to the following version:Author Contributions: Conceptualization, P.R.; methodology, P.R., E.R., S.T.K., G.P., and Z.Z.; formal analyses, P.R., S.T.K., G.P., and Z.Z.; investigation, A.G.; original draft preparation, P.R.; review and editing, P.R., E.R., S.T.K., and G.P. All authors have read and agreed to the published version of the manuscript.The authors have confirmed that the updated authorship meets the ICMJE criteria, the guidelines of which are followed by this journal. We apologize for this error and state that the scientific conclusions are unaffected. The original article has been updated."} +{"text": "A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC.2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life.This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy , four 2-week cycles of FOLFOX or FOLFORI ) followed by neoadjuvant chemoradiotherapy and surgery or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 \u00d7 2.0 Gy or 28 \u00d7 1.8\u2009Gy in radiotherapy-naive patients, and 15 \u00d7 2.0\u2009Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825\u2009mg/mThis trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections. First, induction chemotherapy is associated with toxicityInduction chemotherapy, whether or not combined with neoadjuvant chemoradiotherapy, is increasingly being used in the treatment of LRRC, although evidence for this approach is lacking,,Several studies investigating this treatment regimen in LARC used pCR as the primary endpoint. As in the studies focusing on R0 resection rate, the results were mixed. Some studies described promising pCR rates, whereas others found no effect of adding induction chemotherapy with regard to the pCR rate,,,The available literature regarding induction chemotherapy in addition to chemoradiotherapy for patients with LRRC is limited; currently only three retrospective studiesAlthough the real benefit provided by the addition of induction chemotherapy to chemoradiotherapy and surgery for LRRC has not yet been established, its use is nevertheless increasingThis study will randomize patients with LRRC to receive either induction chemotherapy followed by chemoradiotherapy and surgery or chemoradiotherapy and surgery alone (control arm). As R0 resection is the single most important prognostic factor for survival in patients with LRRC, the main hypothesis to be tested will be an increase in the R0 resection rate in the experimental arm compared with the control arm.This is a multicentre, international, open-label, phase III, parallel-arms study that will randomize eligible patients in a 1 : 1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery or neoadjuvant chemoradiotherapy and surgery alone (control arm). The study is registered with ClinicalTrials.gov (NCT04389086), including the list of centres enrolling for the trial. Surgical treatments will be limited to centres that perform at least 10 resections of LRRC per year (expert centres). Induction chemotherapy and chemoradiotherapy will be administered in expert centres and selected non-expert centres. This is protocol version 4.0, dated 10 December 2020.Patients aged 18\u2009years or older, with resectable histopathologically or clinically proven LRRC after previous partial or total mesorectal resection, with a WHO performance status of 1 or less will be eligible for study participation. Patients with distant metastases at the time of randomization or in the previous 6\u2009months, those who have undergone chemotherapy and/or radiotherapy in the past 6\u2009months, patients with any contraindication to chemotherapy and/or radiotherapy and/or surgery, and those with concurrent malignancies that interfere with the planned study treatment or the prognosis of resected LRRC, will be excluded.Participants will be identified either by physicians in expert centres, or by physicians in non-expert centres who then refer the patients to an expert centre. All eligible patients will be reviewed in a multidisciplinary team (MDT) meeting in an expert centre to assess whether the patient meets the inclusion and exclusion criteria. The multicentre, international involvement in this study will ensure adequate participant enrolment to reach the targeted sample size.Eligible patients who have signed informed consent will be randomized by the coordinating investigator in a 1 : 1 ratio using a software randomization program . Patients will be stratified for previous chemotherapy, previous radiotherapy, and expert centre. After randomization, the treating surgical oncologist will refer the patient to the medical oncologist or radiation oncologist (control arm).Fig. 1, and study interventions and timelines for patients allocated to the experimental and control arms in Tables 1 and 2 respectively.The study flow chart is shown in 2 body-surface area (BSA) intravenously (i.v.) on day 1, capecitabine 1000\u2009mg per m2 BSA, orally, twice daily on days 1\u201314), four 2-week cycles of FOLFOX , or four 2-week cycles of FOLFIRI . The choice of chemotherapy agent will be left to the physician\u2019s discretion.Patients allocated to the experimental arm will start treatment with induction chemotherapy within 4\u2009weeks after randomization. Induction chemotherapy will consist of either three 3-week cycles of CAPOX , and will be similar for radiotherapy-naive and previously irradiated patients. The GTV contains all macroscopic visible tumour, the CTV includes the GTV with a margin of 1\u2009cm, without adjustment of the CTV towards other organs, and the PTV includes the CTV with a margin that can be determined according to local policy. Concomitant chemotherapy will comprise capecitabine, administered orally at a dose of 825\u2009mg/mFour to 6\u2009weeks after the last day of radiotherapy, pelvic MRI will be performed for local restaging and high-dose thoracoabdominal CT for restaging of possible distant metastases. Restaging imaging will be discussed during a dedicated MDT meeting in one of the expert centres. In the event of distant metastases or unresectable local disease, best palliative treatment will be offered. Patients with resectable disease will undergo surgery.,Surgery will be performed by experienced surgical oncologists within 10\u201314\u2009weeks after completion of chemoradiotherapy. The type of surgery will depend on the location of the recurrence and involvement of adjacent structures, and will be left to the discretion of the surgeon. When deemed necessary and feasible by the surgeon and radiation oncologist, intraoperative radiotherapy may be administered by either intraoperative electron beam radiotherapy or high-dose-rate intraoperative brachytherapyPatients will be followed up at 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, 54, and 60\u2009months after surgery. At each follow-up point, a blood sample will be taken to determine the level of carcinoembryonic antigen (CEA). If the CEA level increases compared with the previous CEA level or the level rises above 5.0\u2009\u00b5g/l during follow-up, high-dose thoracoabdominal CT will be performed. At 6, 12, 18, 24, 30, 36, 48, and 60\u2009months after surgery, high-dose thoracoabdominal CT will be performed regardless of the CEA level.All participants will be asked to provide separate informed consent to receive validated quality of life questionnaires ). Patients will receive questionnaires at inclusion, and 3 and 12\u2009months after surgery either by mail or digitally, according to their own preference.All participants will be asked to provide separate informed consent for collection of blood samples and/or tumour tissue for future translational research. If patients give such consent, an additional 20\u2009ml blood will be drawn during regular blood draws before the start of induction chemotherapy , before chemoradiotherapy, before surgery, 3 months after surgery, and once a year during 3 years of follow-up, resulting in seven samples per patient in the experimental arm and six per patient in the control arm. Tumour tissue will be collected by the pathologist, fresh frozen and stored until further use.During the study inclusion period, a monthly central MDT meeting will be organized for quality control. All newly included patients will be discussed during this meeting, which has been designed as a teleconference. In addition, eligible patients will be discussed in the event of uncertainty about whether they meet the inclusion and/or exclusion criteria. Patients who are under treatment at the time of the central MDT meeting, or who have completed treatment, will be discussed only if there are remarkable findings, such as progression of disease resulting in unresectability.The primary outcome of the study is the proportion of patients with a clear resection margin. A resection margin is considered clear (R0), if there are no tumour cells in any of the resection surfaces as determined by microscopy (resection margin more than 0\u2009mm).Secondary outcomes are:3- and 5-year local re-recurrence-free survival, defined as the interval between surgery and local re-recurrence;3- and 5-year progression-free survival, defined as the interval between randomization and progression of local recurrence, local re-recurrence, distant metastases or death;3- and 5-year metastasis-free survival, defined as the interval between randomization and development of distant metastases;3- and 5-year disease-free survival, defined as the interval between surgery and local re-recurrence, distant metastases or death;3- and 5-year overall survival, defined as the interval between randomization and death;pathological response, graded according to the Mandard grading systemradiological response, scored according to the magnetic resonance tumour regression grade (mrTRG);compliance rate with induction chemotherapy ;toxicity of induction chemotherapy, scored from day 1 of the first cycle of induction chemotherapy until 1 month after the final administration, and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0;compliance rate with chemoradiotherapy, calculated as the total radiotherapy dose received divided by the total planned dose;toxicity of chemoradiotherapy, scored from start of radiotherapy until 3 months after the final dose of radiotherapy, and graded according to CTCAE version 5.0;number of patients undergoing surgery;surgical characteristics ;major surgical morbidity rate scored from the date of surgery to 3 months after surgery, and graded according to the Clavien\u2013Dindo classificationquality of life, assessed with EQ-5D-5L\u2122, QLQ-C30 and QLQ-CR29 questionnaires at inclusion, and at 3 and 12 months after surgery; andcost-effectiveness and cost\u2013utility, based on Dutch costing guidelines for healthcare, the case report forms, and the EQ-5D-5L\u2122 questionnaire.,Currently, an R0 resection is achieved in approximately 60 per cent of patients undergoing surgery after treatment with neoadjuvant chemoradiotherapyP < 0.050 will be classified as statistically significant. Patients initially randomized but considered ineligible afterwards, based on information that should have been available before randomization, will be excluded from all analyses.Demographics, patient, and tumour characteristics will be presented for each treatment arm. Continuous data will be reported as mean (standard deviation) or median , depending on the distribution. Categorical data will be reported as count with percentage. All statistical tests will be two-sided and Analysis of the primary endpoint of this study, the proportion of patients with an R0 resection, will be based on the intention-to-treat principle using Fisher\u2019s exact test. In addition, a per-protocol analysis will be performed as a sensitivity analysis.All survival curves will be constructed according to the Kaplan\u2013Meier method, and the log rank test will be used to compare treatment arms, adjusting for stratification factors at randomisation . In addition, hazard ratios will be calculated using a Cox proportional hazards regression model, adjusting for stratification factors. Metastasis-free survival, progression-free survival, and overall survival will be based on the intention-to-treat group. Local re-recurrence free survival and disease-free survival analyses will include only patients who underwent surgery.Data on surgical characteristics, histopathological characteristics, and major surgical morbidity will be presented by treatment arm, and will be derived only for patients who underwent surgery. The number of patients undergoing surgery will be analysed in the intention-to-treat population. Comparison between treatment arms will be done by means of Fisher\u2019s exact test.The absolute and relative incidence of toxicities related to the administration of induction chemotherapy or chemoradiotherapy will be presented by treatment arm, and analysed in all patients who received at least one dose of neoadjuvant chemotherapy or chemoradiotherapy (control arm). Comparison between treatment arms will be done by means of Fisher\u2019s exact test.Comparison of health-related quality of life between the two treatment arms at baseline and over time will be performed by means of a random-effects regression model and will be based on the intention-to-treat group.Incremental cost-effectiveness and cost\u2013utility ratios will be calculated for the extra costs per additional surviving patient and the extra costs per additional quality-adjusted life year respectively. Non-parametric bootstrapping, drawing samples of the same size as the original samples and with replacement, will be applied to generate 95 per cent confidence intervals for (differences in) costs and health outcomes. Cost-effectiveness planes will be displayed and cost-effectiveness acceptability curves drawn for willingness-to-pay values up to \u20ac100 000.A central study database (Netherlands Comprehensive Cancer Institute (IKNL), Utrecht, the Netherlands) with an electronic case report form will be used to record all data required to address the primary and secondary objectives. Local data management will be undertaken by the IKNL or an in-hospital qualified local data management team. Questionnaires will be collected centrally by the coordinating investigators and recorded using an ISO 27001-certified information security system .A central data safety monitoring board (DSMB), consisting of a medical oncologist, a surgical oncologist, and a statistician, has been assigned to monitor the safety of study participants, and to protect the validity and credibility of the study. Members of the DMSB are independent and have no competing interest. After 100 patients have undergone surgery, the DSMB will review the safety data. Inclusion will be continued during interim analysis. At the interim analysis, the number of patients who cannot complete the full course of chemoradiotherapy and the number of patients with major postoperative morbidity (Clavien\u2013Dindo grade at least III) will be tabulated and discussed. Examining these safety and logistical aspects will not affect the total sample size or the actual \u03b1 level at final analysis. After the interim analysis, the DSMB will recommend to the trial steering committee (TSC) whether the study should be continued or terminated. Should the TSC decide not to fully implement the advice of the DSMB, it must explain to the medical ethical committee why (part of) the advice of the DSMB will not be followed.https://www.toetsingonline.nl) to the medical ethical committee that approved the protocol. The time window for recording SAEs and SUSARs is from randomization until 3\u2009months after surgery, or 1\u2009month after the last day of neoadjuvant treatment for patients with progressive disease who did not undergo surgery. SAEs and SUSARs will be followed up until resolved or until a stable situation has been reached.All serious adverse events (SAEs) or suspected unexpected serious adverse events (SUSARs) will be reported by the physician to the study coordinator within 24\u2009h and without undue delay after obtaining knowledge of the event. The coordinating investigator will report SAEs through the web portal ToetsingOnline , the Dutch Competent Authority , and all institutional review boards of the participating study centres. The study will be submitted to the competent authorities, central ethical committees, and institutional review boards of the participating international centres.All substantial amendments will be notified to the investigators, institutional review boards of all study centres, the medical ethical committee, the competent authority, and trial registries.Informed consent will be obtained by the treating physician in one of the expert centres. Patients will be allowed to provide separate permission for the collection of blood and/or tissue samples for translational research, and for receiving quality of life questionnaires.Individual patient information obtained as a result of this study is considered confidential and its handling will conform with the Dutch Personal Data Protection Act (AVG). Patients\u2019 confidentiality will be ensured by use of study numbers.The investigators declare no financial or other competing interests.Access to the final data set is reserved for the central data manager, study statistician, coordinating investigator, and trial steering committee. There are no contractual agreements that limit this access.The study has no provision for ancillary or post-study care.The results of this study will be dispersed by publishing the results in international peer-reviewed journals and by offering an abstract to international oncological congresses. Any publication, abstract or presentation based on patients included in this study must be approved by the trial steering committee and coordinating investigator. The principal manuscript resulting from this study will be published by group authorship (PelvEx Collaborative).This randomised controlled trial will investigate the role of induction chemotherapy in patients with LRRC. The results of this study will demonstrate whether or not induction chemotherapy has additional value in the treatment of patients with non-metastasized resectable LRRC with regard to the R0 resection rate; this group of patients has had a poor prognosis so far.,The rationale for R0 resection as the primary outcome in this study was based on the fact that R0 resection is the most important prognostic factor for survival in patients undergoing surgery for LRRC. Ultimately, an increase in R0 resection rate should lead to an improvement in local re-recurrence-free and overall survival. Because of the relatively rarity of LRRC as a result of improvements in the treatment of primary rectal cancer, and the fact that approximately 50 per cent of patients with LRRC will not be eligible for inclusion in this study owing to distant metastases or unresectable local disease, survival parameters could not be used as the primary outcome, as power calculations showed that the sample size would be unfeasible,,,,The rationale for the induction chemotherapy regimen chosen in this study is based on studies in (metastatic) colorectal cancer. In those first-line studiesversus induction chemotherapy and surgery in previously irradiated patients. The primary outcome measure is the R0 resection rate. The Japanese JCOG1801 study is randomizing between surgery followed by adjuvant chemotherapy versus neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy (CAPOX/FOLFOX) in radiotherapy-naive patients, with local recurrence-free survival as the primary outcome measure. The Chinese NARC study is randomizing between surgery followed by adjuvant chemotherapy versus neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy, with overall survival as the primary outcome measure. The results of these studies will be actively monitored to assess whether their results have any implications for the present study protocol.There are three other ongoing trials investigating the optimal treatment for patients with LRRC. The French GRECCAR15 study is randomizing between induction chemotherapy, chemoreirradiation, and surgery Members of the PelvEx Collaborative: E. L. K. Voogt, S. Nordkamp, A. G. J. Aalbers, T. Buffart, G. J. Creemers, C. A. M. Marijnen, C. Verhoef, K. Havenga, F. A. Holman, M. Kusters, A. W. K. S. Marinelli, J. Melenhorst, N. Abdul Aziz, N. Abecasis, M. Abraham-Nordling, T. Akiyoshi, W. Alberda, M. Albert, M. Andric, E. Angenete, A. Antoniou, R. Auer, K. K. Austin, O. Aziz, R. P. Baker, M. Bali, G. Baseckas, B. Bebington, M. Bedford, B. K. Bednarski, G. L. Beets, R. G. H. Beets-Tan, M. Berb\u00e9e, J. Berg, P. L. Berg, J. Beynon, S. Biondo, J. G. Bloemen, K. Boyle, L. Bordeianou, A. B. Bremers, M. Brunner, P. Buchwald, A. Bui, A. Burgess, D. Burling, E. Burns, N. Campain, S. Carvalhal, L. Castro, A. Caycedo-Marulanda, H. M. Ceha, K. K. L. Chan, G. J. Chang, M. Chang, M. H. Chew, A. K. Chok, P. Chong, H. K. Christensen, H. Clouston, M. Codd, D. Collins, A. J. Colquhoun, A. Corr, M. Coscia, M. Cosimelli, P. E. Coyne, A. S. L. P. Crobach, R. M. P. H. Crolla, R. S. Croner, L. Damjanovic, I. R. Daniels, M. Davies, R. J. Davies, C. P. Delaney, M. A. J. de Roos, J. H. W. de Wilt, M. D. den Hartogh, Q. Denost, P. Deseyne, C. Deutsch, R. de Vos tot Nederveen Cappel, M. de Vries, M. Dieters, D. Dietz, S. Domingo, M. Doukas, E. J. Dozois, M. Duff, T. Eglinton, J. M. Enrique-Navascues, E. Espin-Basany, M. D. Evans, B. Eyj\u00f3lfsd\u00f3ttir, M. Fahy, N. S. Fearnhead, S. Feshtali, K. Flatmark, F. Fleming, J. Folkesson, F. A. Frizelle, J. E. Fr\u00f6din, M. A. Gallego, E. Garcia-Granero, J. L. Garcia-Sabrido, K. Geboes, L. Gentilini, M. L. George, V. George, L. Ghouti, F. Giner, N. Ginther, T. Glyn, R. Glynn, T. Golda, H. I. Grabsch, B. Griffiths, D. A. Harris, J. A.W. Hagemans, V. Hanchanale, D. P. Harji, R. M. Helewa, H. Helgason, G. Hellawell, A. G. Heriot, S. Heyman, D. Hochman, C. Hoff, W. Hohenberger, T. Holm, R. Hompes, K. Horsthuis, G. Hospers, J. Houwers, H. Iversen, J. T. Jenkins, S. Kaffenberger, G. V. Kandaswamy, S. Kapur, Y. Kanemitsu, G. Kats-Ugurlu, S. R. Kelley, D. S. Keller, M. E. Kelly, K. Keymeulen, M. S. Khan, H. Kim, H. J. Kim, C. E. Koh, N. F. M. Kok, R. Kokelaar, C. Kontovounisios, H. \u00d8. Kristensen, H. M. Kroon, S. Kumar, V. Lago, Z. Lakkis, T. Lamberg, S. G. Larsen, D. W. Larson, W. L. Law, S. Laurberg, P. J. Lee, M. M. Leseman-Hoogenboom, M. Limbert, M. L. Lydrup, A. Lyons, A. C. Lynch, C. Mantyh, K. L. Mathis, C. F. S. Margues, A. Martling, O. W. M. Meijer, W. J. H. J. Meijerink, A. Merchea, S. Merkel, A. M. Mehta, D. R. McArthur, F. D. McDermott, J. S. McGrath, S. Malde, A. Mirnezami, J. R.T. Monson, J. R. Morton, J. Nederend, I. Negoi, J. W. M. Neto, J. L. Ng, B. Nguyen, M. B. Nielsen, G. A. P. Nieuwenhuijzen, P. J. Nilsson, M. L. Nilsson, S. Oei, A. Oliver, S. T. O\u2019Dwyer, V. Oppedijk, G. Palmer, E. Pappou, J. Park, D. Patsouras, G. Pellino, A. C. Peterson, H. M. U. Peulen, G. Poggioli, D. Proud, M. Quinn, A. Quyn, N. Rajendran, R. W. Radwan, S. Rasheed, P. C. Rasmussen, E. Rausa, S. E. Regenbogen, A. Renehan, M. C. Richir, R. Rocha, M. Rochester, J. Rohila, J. Rothbarth, M. Rottoli, C. Roxburgh, T. Rozema, B. Safar, P. M. Sagar, A. Sahai, A. Saklani, T. Sammour, R. Sayyed, A. M. P. Schizas, E. Schwarzkopf, V. Scripcariu, C. Selvasekar, I. Shaikh, D. Shida, A. Simpson, T. Skeie-Jensen, J. J. G. Slangen, N. J. Smart, P. Smart, J. J. Smith, P. Snaebjornsson, A. M. Solbakken, M. J. Solomon, M. M. S\u00f8rensen, L. Sorrentino, F. M. Speetjens, E. J. Spillenaar Bilgen, S. R. Steele, D. Steffens, K. Stitzenberg, L. Stocchi, N. A. Stylianides, T. Swartling, H. Sumrien, P. A. Sutton, T. Swartking, E. J. Tan, C. Taylor, P. P. Tekkis, J. Teras, V. Terpstra, R. Thurairaja, E. L. Toh, P. Tsarkov, Y. Tsukada, S. Tsukamoto, J. J. Tuech, W. H. Turner, J. B. Tuynman, E. B. van Duyn, W. M. U. van Grevenstein, N. C. T. van Grieken, L. Valkenburg-van Iersel, G. van Lijnschoten, E. van Meerten, G. H. van Ramshorst, H. L. van Westreenen, D. van Zoggel, W. Vasquez-Jimenez, L. A. Velema, E. Verdaasdonk, H. M. W. Verheul, K. S. Versteeg, G. Vizzielli, K. Uehara, C. Wakeman, S. Warrier, H. H. Wasmuth, K. Weber, M. R. Weiser, J. M. D. Wheeler, N. A. T. Wijffels, J. Wild, J. M. W E. Willems, M. Wilson, D. C. Winter, A. Wolthuis, M. L. Wumkes, H. Yano, B. Yip, J. Yip, R. N. Yoo, M. A. Zappa, D. D. E. Zimmerman, H. J. T. Rutten, J. W. A. Burger.This study is funded by the highly specialized care and research programme (TZO programme) of the Netherlands Organization for Health Research and Development (ZonMw).Disclosure. The authors declare no conflict of interest."} +{"text": "Overall, seroprevalence was 47.7% (231/484) while zoonotic genotype 3 HEV RNA was detected in 16.0% (20/125) of slaughtered pigs. This is the first report to highlight occurrence of HEV infection in domestic pigs in Zambia. This finding suggests possible contamination of the pork supply chain. Moreover, there is a potential risk of zoonotic transmission of HEV to abattoir workers, pig farmers and handlers.While evidence suggests presence of HEV infection in humans in Zambia, currently, there is no information on its occurrence in domestic pigs. Here, we investigated the presence of HEV antibodies and genome in domestic pigs in Zambia. Sera ( Orthohepevirus A species are known to infect humans, of the eight genotypes identified so far, only genotypes 3, 4 and 7 infect both humans and animals [via contaminated food or water and is commonly associated with acute viral hepatitis in humans [Hepatitis E virus (HEV) causes hepatitis E, an emerging disease that is endemic in developing and developed countries worldwide. A number of animal species, including wild boar, pigs, camels, and deer are reservoirs for HEV . Althoug animals ,4\u20138. Gen animals ,4. Howev animals ,7. HEV in humans . Occasion humans . While tn humans . In Zambn humans , althougn\u2009=\u2009176) and exotic pigs (landrace) at a commercial farm (n\u2009=\u2009176) while 132 samples were collected from indigenous free-range pigs in Katete District of Eastern Province. Additionally, fecal (n\u2009=\u200925) and liver (n\u2009=\u2009100) samples were collected from pigs (n\u2009=\u2009125) at Chibolya abattoir in December 2019.A total of 484 serum samples were collected from adult domestic pigs in Lusaka and Eastern Province of Zambia between May 2017 and December 2019. Of these, 352 samples were obtained from Lusaka Province from crossbred pigs (landrace/large white) at Chibolya abattoir (https://www.qiagen.com) as per manufacturer\u2019s protocol. Screening for HEV genome was conducted by nested RT\u2013PCR targeting the partial open reading frame (ORF) 1 and 2 genes [https://www.megasoftware.net). The sequences were deposited in GenBank under accession numbers LC653123-LC653139 (ORF1) and LC621322-LC621339 (ORF2). Simple logistic regression was used to model the dependency of HEV seropositivity on the pig management system .Serologic analysis for HEV antibodies was performed with an Indirect Multi-species ELISA which is based on the recombinant capsid protein of HEV-3. The ELISA has a reported test specificity of 100%. RNA was extracted from liver and fecal samples using the RNeasy Plus Mini Kit and fecal RNeasy PowerMicrobiome Kit in slaughtered pigs from Chibolya abattoir compared to that in pigs from a commercial farm . There was no significant difference in seroprevalence rates between indigenous free-range pigs from Katete District in Eastern Province and crossbred pigs from Chibolya abattoir , possibly due to contrasting types of pig management systems. Pigs from Chibolya abattoir and Katete District are raised under semi-confined and free-range types of management systems, respectively. While the reasons for the observed high seroprevalence (47.7%) are not clear, the ELISA assay and type of pig management system may have contributed to the observed high seroprevalence. Similarly, as previously observed [HEV RNA was detected in both fecal and liver 12%; 12/100) samples. However, the relatively low HEV RNA positivity (16%) in slaughtered pigs was probably due to virus clearance in adult pigs as previously observed [%; 12/100To our knowledge, this is the first report to highlight the occurrence of zoonotic HEV-3 infection in domestic pigs in Zambia. A similar study in Madagascar found probable evidence of virus transmission from infected pigs to abattoir workers . FurtherConceptualization, H.M.C., M.S., W.W.H., P.F., E.S., H.S., and Y.O., methodology, H.M.C., M.S., W.M., E.S., H.S., and Y.O., investigation, H.M.C., M.S., W.M., M.K., K.E.M., H.H., Y.Q., D.S., E.S., H.S., and Y.O., Data curation, H.M.C., M.S., W.M., M.K., M.S., E.S., H.S., and Y.O., Funding acquisition, H.M.C., M.S., W.W.H., P.F., E.S., H.S., and Y.O., supervision, M.S., W.W.H., E.S., H.S., and Y.O. All authors participated in revising and approving the final version of the manuscript.Click here for additional data file."} +{"text": "Many processes in living organisms are subject to periodic oscillations at different hierarchical levelsof their organization: from molecular-genetic to population and ecological. Oscillatory processes are responsiblefor cell cycles in both prokaryotes and eukaryotes, for circadian rhythms, for synchronous coupling of respirationwith cardiac contractions, etc. Fluctuations in the numbers of organisms in natural populations can be caused bythe populations\u2019 own properties, their age structure, and ecological relationships with other species. Along withexperimental approaches, mathematical and computer modeling is widely used to study oscillating biological systems. This paper presents classical mathematical models that describe oscillatory behavior in biological systems.Methods for the search for oscillatory molecular-genetic systems are presented by the example of their specialcase \u2013 oscillatory enzymatic systems. Factors influencing the cyclic dynamics in living systems, typical not onlyof the molecular-genetic level, but of higher levels of organization as well, are considered. Application of different ways to describe gene networks for modeling oscillatory molecular-genetic systems is considered, where themost important factor for the emergence of cyclic behavior is the presence of feedback. Techniques for findingpotentially oscillatory enzymatic systems are presented. Using the method described in the article, we present andanalyze, in a step-by-step manner, first the structural models (graphs) of gene networks and then the reconstruction of the mathematical models and computational experiments with them. Structural models are ideally suitedfor the tasks of an automatic search for potential oscillating contours (linked subgraphs), whose structure cancorrespond to the mathematical model of the molecular-genetic system that demonstrates oscillatory behavior indynamics. At the same time, it is the numerical study of mathematical models for the selected contours that makesit possible to confirm the presence of stable limit cycles in them. As an example of application of the technology, a network of 300 metabolic reactions of the bacterium Escherichia coli was analyzed using mathematical andcomputer modeling tools. In particular, oscillatory behavior was shown for a loop whose reactions are part of thetryptophan biosynthesis pathway Many processes in living organisms are subject to periodicoscillations at different hierarchical levels of their organization: from the molecular-genetic to the population and ecological levels. For example, at the molecular-genetic level,there are oscillations in the concentrations of p53, a proteininvolved in apoptosis or cell cycle delay in DNA damage, andits inhibitor Mdm2 . Thereare also fluctuations in concentrations of hormones in thecell, such as melatonin , prolactin,total cholesterol , etc.; concentrations oflow molecular weight compounds, such as intracellular andintercellular calcium ion concentrations, can also oscillateOne well-known example of organism-wide periodic processes is circadian rhythms, for the work on which the 2017Nobel Prize in Physiology or Medicine was awarded . Jeffrey C. Hall, Michael Rosbash, and Michael W.Young discovered the period gene in Drosophila melanogaster, which is regulated through feedback by the PER protein underlying circadian rhythm.In the article , the authors considered genes located in liver and kidney cells that are overexpressed with a certain periodicity during the 24-hour cycle.In a subsequent paper, the authors provided an overview ofvarious mathematical models used to model the autonomouscircadian clock in mammalian cells .At the cellular level, cyclic processes can include cellcycles in both prokaryotes and eukaryotes .Such important cyclic processes as heartbeat , respiration, as well as synchronous relationshipbetween respiration and heartbeat ,photosynthesis and other similar processes occur at the level of an individual organ or functionalsystems of an organism.Population waves are a classic exampleof cyclic processes at the population level of organization.Fluctuations in the number of organisms in natural populations can be caused both by external environmental factorsand by the population\u2019s own properties, its age structure,and ecological relationships with other species. A naturalfactor such as seasonal periodicity plays an important role inthe cyclic processes of the population level, influencing themigration of birds, falling into anabiosis, the appearance andfall of leaves, etc.Thus, in the article , the authors considered the cyclicity in the population dynamicsof the red vole, which varies depending on the geographicalhabitat and external conditions in the area. And in the paper, using a stochastic model, the authorsconsidered how the population size changes when harmfulfood resources are consumed. The investigation of populationdynamics, often cyclical, is one of the most studied processes,both by empirical methods and with the help of mathematicalmethods, including modeling .Finally, biogeochemical cycles, i. e., processes of dynamicexchange of chemicals between organisms from prokaryotesto higher animals and plants and elements of the biosphere can be classified as cyclic processes atthe ecological level .Cyclical processes in biology are investigated using experimental and theoretical methods. Mathematical modelingis one of the main methods for their investigation, particularlyin finding areas of stationary, oscillatory, and possibly chaoticbehavior .The first works devoted to oscillatory biochemical processesbelong to Alfred Lotka . Lotka described the dynamics of biochemical processes using systems of nonlinearordinary differential equations. Around the same time, VitoVolterra, independently of Lotka, developed the same models,but in application to population-ecological problems. Thesemodels were later called the \u201cLotka\u2013Volterra models\u201d. Furtherstudy of oscillatory chemical processes led to the discoveryof Belousov\u2013Zhabotinsky type systems, in which oscillationsoccur not only in time but also in space, and, therefore, canbe described not only by ordinary differential equations, butalso by partial differential equations .This article presents a review of classical mathematicalmodels that describe oscillatory behavior in biological systemsand gives illustrations of methods for finding such systemsusing enzymatic oscillatory systems as an example. The roleof gene networks in modeling oscillatory molecular-geneticsystems is discussed. The factors influencing the presence orabsence of oscillatory behavior in various molecular-geneticsystems are given.Among the first mathematical approaches describing oscillatory processes are models that have already become classicalin the field of mathematical biology . Inone of the papers devoted to the theory of periodic reactions,Lotka studied a chemical reaction of the form (1):where X \u2192 Y is an autocatalytic process. Based on the lawof mass action, Lotka described this reaction by the followingdifferential equations (Formula 2):where k0, k1, k2 are the constant parameters and x, y are theconcentrations of chemicals.The following model, described by Lotka andthen independently formulated by Volterra ,expresses two autocatalytic reactions (i. e. A \u2192 X and X \u2192 Y).The Lotka\u2013Volterra model has the following form (3):where a, b, c, d are the rates of transformation of some substances into others, x, y are the concentrations of chemicals.This model is also known as the \u201cpredator\u2013prey system\u201d,which is used in population dynamics to explain periodicfluctuations in the abundance of individuals in populations.In the same period a paper with the van der Pol and vander Mark oscillator model was published . They modeled the heart as three connectedrelaxation systems: sinus, atrium and ventricle. As such a system, the authors chose a system consisting of a neon lamp,a condenser, a resistance, and a battery, which is capable ofproducing relaxation oscillations. However, this system simulates only some modes of heart operation due to the complexity of the object under study. The model is described byan equation of the form (4):where \u03b1 is a positive value, which is an oscillator parameter(responsible for non-linearity and damping of oscillations),\u03c9 \u2013 oscillation frequency, v \u2013 the value corresponding to theheart rhythm signal.This model is noteworthy because it has found an application not only in biology problems, but also in physics and othersciences. For example, the review presented a number of problems in which this oscillator wasapplied; in particular, the authors gave details on modeling human body processes, such as colonic myoelectric activity andprocesses of excitation and inhibition of neurons. In the paper, the authors considered three van derPol oscillators to study the in-phase mode, which correspondsto the synchronized periodic behavior of circadian rhythms.Moreover, two of them correspond to the eye models, and thethird oscillator is a model of the brain , through which the interconnection of thefirst two is performed. They considered the periodic changeof melatonin concentration under the influence of circadianrhythms as a possible scheme of connection between the eyesand the pineal gland.In 1965, an article by Brian Goodwin was published, which raised the question of the oscillatorymotion role in the organization of cellular processes overtime. For the mathematical study of oscillatory behavior inmodel systems involving enzyme regulation processes, heintroduced certain concepts of thermodynamic nature. Inthe article, the author cited a model of the process of geneticcontrol of enzyme synthesis (Formula (5)):where Xiis an mRNA concentration of the i\u200ath species, Yiisa protein (repressor) concentration of the i\u200ath species, ki\u2013 parameter, which describes the interactions between the DNAand the repressor.Another classic example is the Higgins model of oscillatory reactions in the glycolysis system, thescheme of which is shown below (Formula (6)):Here GLU, F6P, FDP, GAP are designations of biochemicalsubstances that enter into reactions, E\u200a* 1 \u2013 the active form ofthe enzyme (phosphofructokinase), E\u200a+ 1 \u2013 the inactive form ofthe enzyme, E2 \u2013 the enzyme that is a combination of aldolaseand triose phosphate isomeraseHiggins considered general pathway types of enzymaticreactions in glycolysis in which the chemical mechanismexhibits oscillatory behavior. Therefore, in his work, he takesinto account the following conditions: (1) one of the chemicalsmust activate its own production (assuming the concentrationof the second substance is constant); (2) the second substancemust tend to inactivate its own net production; (3) there mustbe a cross-coupling of the interaction of substances. If anincrease in the first substance activates the production of thesecond substance, then an increase in the second substanceinhibits the production of the first, and vice versaSel\u2019kov in his classic article , in accordancewith the mass action law, gave a mathematical model of theglycolytic system based on the phosphofructokinase (PFK)transformations (Formula (7)):where s1 \u2013 the substrate (ATP), v1 \u2013 the inf\u200alow rate of the substrate from some source, s2 \u2013 the product (ADP), v2 = k2s2 \u2013 theoutflow rate of the product from the system, e \u2013 free enzyme(phosphofructokinase), which is inactive on its own, butbecomes active when combined with product molecules asa complex \u2013 ES\u200a\u03b32 , x1 \u2013 the molecule of the complex (ES\u200a\u03b32),x2 \u2013 the molecule of enzyme-substrate complex (S1ES\u200a\u03b32 ),s\u03b32 \u2013 product molecules that enter into a complex with the freeenzyme, \u03b3 > 1 \u2013 the parameter responsible for the number ofthe product molecules, k+1, k+2, k+3 \u2013 rates of direct reactions,k\u20131, k\u20133 \u2013 rates of reverse reactions, t \u2013 time.Goldbeter and Lefever presenteda model of the glycolytic system, which is a generalization ofthe models presented by Higgins andSel\u2019kov . The model is based on the mechanismof positive feedback, namely, the activation of the product bythe enzyme PFK.In the article , the authors not onlyanalyzed the allosteric model of the oscillatory reaction ofphosphofructokinase, but also made experimental verificationof theoretical predictions. The data obtained for the modelagreed well with the experimental data.In 2000, a model of a yeast population consisting of a smallensemble of individual cells was presented to describe thephenomenon of synchronization of glycolytic oscillations. Inthis case, the communication between the cells was performed through the exchange of acetaldehyde . Glycolytic oscillations were also studied using stochastic methodsand chaos theory in ; Selkov\u2019sminimal model was taken as the basis, and in the article a two-dimensional Higgins model was used.In biochemistry, the processes of changing the concentrationof ions in cells, which can increase or decrease the activityof enzymes, participate in the metabolism of carbohydrates,lipids and proteins, as well as play an important role in signaltransduction through signaling pathways and are responsiblefor cell excitability, are actively studied. One of such processesis periodic changes in calcium ion concentrations. Anumber ofmathematical models have been developed to study these periodic processes. Amodel describing calcium ion concentrationfluctuations was first proposed in (Formula (8)):where Z \u2013 the cytosolic calcium concentration, Y \u2013 the calciumconcentration in IP3 endoplasmicreticulum, vi \u2013 reaction rates.They analyzed the conditions for the emergence of stablefluctuations based on the mechanism of calcium-inducedcalcium release (CICR). In a number of studies , theauthors continued their researches of calcium concentrationfluctuations based on the same minimal model.At the same time, papers in which the authors investigated fluctuations in calcium concentrations by considering the mechanism of inositolcross-coupling (ICC) IP3 with extracellular, cytosolic, andendoplasmic Ca2+ have been coming out. Lavrentovich andHemkin proposed a modelfor spontaneous Ca2+ oscillations in astrocytes that takes intoaccount the mechanisms presented above as well as IP3 production in a receptor-independent mannerAfter Goldbeter and Dupont had published their results, theauthors of the article tested the hypothesisthat in unexcited cells the amplitudes of oscillatory processescan be cell type-specific and vary with Ca2+ diffusion. Theyperformed their study using stochastic computer modeling ona two-dimensional Ca2+ oscillation model.Analysis of oscillatory processes in living systems showsthat the most important factor in the emergence of cyclic behavior is a feedback in the system .Adistinction is made between positive and negative feedbacks,which was once discussed by Goodwin, Walter, Cardon, Iberalland other researchers . Both types of these feedbacks caninfluence the emergence of cyclic dynamics in the system, ashas been shown in works .At the molecular level, the principle of feedback regulatesa huge number of enzymatic reactions simultaneously goingon in a living cell, the rate of which can be affected by suchcompounds as inhibitors, activators, cofactors, allosteric effectors, etc. As early as 1913 an article by biochemists Michaelis and Menten was published, inwhich the scientists derived the equation for the dependence ofthe reaction rates catalyzed by the enzyme on the concentration of the substrate. Later, the researchers have showed that,using computational methods, optimizing the parameters of theequation by approximating the model data to the experimentaldata corresponds to the results, which were obtained manuallyby Michaelis and Menten for their constant.Not long ago, a review was conducted of how methodsfor quantitative analysis of enzyme kinetics have emerged,changed, and been modified over a century .In the same year an article examinedthe influence of Michaelis\u2013Menten kinetics on oscillatorybehavior in enzymatic systems, namely, in glycolysis fromphosphofructokinase activity and in the cell cycle from cyclindependent kinasesNov\u00e1k and Tyson reviewed examples of oscillatory processes and formulated the necessary conditions for oscillations in the system: negative feedback, time delay, sufficient\u2018nonlinearity\u2019 of the reaction kinetics and proper balancingof the timescales of opposing chemical reactions .In a recent review , the authors compiled various approaches to modeling the dynamics of thebehavior of biochemical regulatory networks that have beendeveloped over the past 50 years. Models such as Boolean ones, models consisting of piecewise-linear or fullynonlinear ordinary differential equations, and stochastic models (including hybrid deterministic/stochastic approaches) areconsidered. The authors focused on two approaches: modelinggenetic control systems as networks of Boolean switches andmetabolic and signaling networks using systems of nonlinearordinary differential equations. They considered only spatiallyhomogeneous systems. The authors showed the advantagesand disadvantages of each method depending on the type andamount of available experimental information.The models, which we reviewed in this section, are summarized in Table 1.Modeling of metabolism is often associated with modeling ofgenetic regulation .The concept of gene networks plays an integrative role in thiscase .The main task of the theory of gene networks is to identifycausal relationships between the structural and functionalorganization of gene networks and their dynamic properties. The structural andfunctional organization of gene networks is understood as aset of molecular-genetic and biochemical processes, while thedynamic properties are understood as the kinetics of changesin the concentrations of end products over time.Computer analysis and modeling of small gene networks,especially hypothetical gene networks, provides very valuableinformation for understanding the fundamental features ofthe dynamics of regulatory gene networks. Likhoshvai andhis colleagues developed a theory linking the structural andfunctional organization of hypothetical gene networks withtheir dynamics . Namely, theconcept of a hypothetical gene network was defined; rulesfor formalizing the description and assembling mathematicalmodels from them are given. The -criterion for predictingsome properties of the models by the structure of the network graph is formulated; 4 classes of the hypothetical gene networkare introduced according to the types of regulatory links in thenetwork; and analytical and numerical studies of the modelsfor each class of the hypothetical gene network are given.In particular, it was first theoretically and then numericallydemonstrated how the appearance of a new regulatory linkleads to a qualitative change in the dynamics of the gene network . Thus, the addition of another regulatory linkin the gene network cardinally changes the possible modesof functioning of this network \u2013 if only one stationary statewas possible in the initial network, then after adding anotherregulatory link, there are already two possible states \u2013 stationary (as in the previous case) and cyclic mode.The connection between the structures of gene networksand the presence of dynamic cycles in them has been studiedfor many years. In particular, the connection between networkstructure and cyclic dynamics has been theoretically shown. Elowitz and Leibler designed and studied a geneticnetwork of a repressilator, in which the network under studyis locked into a cycle of interactions based on the principleof negative feedbacks. The authors experimentally showedthat this type of network has an oscillatory mode of behavior.In the Sobolev Institute of Mathematics SB RAS is studiedthe qualitative theory of dynamical systems describing variousgene networks that are regulated by feedbacks. Golubyatnikov and his colleagues have studied in their works the existence and uniqueness of periodic solutions, existence of closed trajectories, cycle stability,etc. in such systems. The interest in the analysis of the behaviorof such trajectories is to correspond them to the modes offunctioning of gene networks. An article showed that oscillatory trajectories are present in models of the simplest circular gene networks and they are stable.In this paragraph, we describe the algorithm for searching theoscillatory molecular-genetic systems . It uses information resources both developedby the authors and widely known in systems biology. In particular, the MAMMOTh database is a source of structural andmathematical models of Escherichia coli metabolic reactions. Cytoscape (cytoscape.org) is a toolfor working with structural models and Copasi is a tool for reconstructing and investigating mathematical models. Python (python.org) is both a data processing tooland a link between the steps.The input of the algorithm takes a structural model \u2013 a genenetwork graph with typing of model elements and their relations. There are two types of nodes in the graph: biologicalsubstances (molecules and their groups) and processes (orreactions). The edges specify the following relations betweenthe nodes: substance is a substrate in a reaction, substance isa product of a reaction, and substance is a regulator of a reaction. This information can be obtained directly from models inSBML , SBGN ,from other tools for building structural models, or from Pythonscripts. To date, any database that has information on metabolic pathways and molecular-genetic systems models can beused as a data source. The best-known databases are KEGG, GeneNet , MetaCyc, EcoCyc , BioModels, etcIn this article, we considered a special case of moleculargenetic systems \u2013 the oscillatory enzymatic systems. Analysisof the literature allows us to identifythe following key characteristics of potentially oscillatingcontours: (1) the closure of the contour ; (2) the orientation of the contour in one direction, with the last node havingan edge of regulatory inhibitory influence on the first nodein the contour .A graph of 300 subsystems representing modelsof E. coli metabolic reactions taken from the MAMMOThdatabase was taken as initial dataThe construction of a mathematical model of a potentiallyoscillating contour can be performed both in general-purposeengineering simulation environments or in specialized environments designed for the simulation of molecular-genetic systems , VCELL , etc.). The advantage of the latter is the readylibrary of tools for reconstruction, computational experimentsand model analysis.Six potentially oscillating contours were found in the analyzed graph, and during the numerical analysis of the reconstructed mathematical model oscillatory behavior was shownfor only one of them . The mathematical model of thecontour was constructed based on the reactions related to themetabolic pathway of tryptophan biosynthesis (Formula (9)):Here CHOR, GLN, PYR, GLU, AN, PRPP, NPRAN, PPI,CPAD5P, IGP, SER, T3P1, TRP \u2013 before the semicolon arethe designations of the biochemical substances involved in thereaction, and after that are regulators of reactions. Full namesof substances are given in Table 2.The model was built in Copasi and consists of 5 differential equations. (Formula (10))where kD_\u201csubstance name\u201d are degradation constants of corresponding substances, parameters TRP_power and TRP_denominator varied in the process of searching for oscillatorybehavior of the system. The given numerical parameters weretaken from the MAMMOTh database.The mathematical model of only one of the six contoursfound exhibits with oscillatory behavior. As we considered,a network consisting of only 300 enzymatic reactions, whichhad mathematical models adapted to the experimental data,may explain such a small number of contours. In turn, thereare currently not many such mathematical models for describing the enzymatic reactions of biological systems. Thousandsof existing models presented in databases are often automatically generated, as in the Path2Models project for thebiomodels.net database, for example. Experimentally measured kinetic parameters of biochemical reactions are becoming increasingly scarce. Using graphs with higher dimensionality (full-genome models) to study oscillatory behaviorwill increase the number of variants to be tested, but this willrequire additional consideration of the regulatory componentof genetic synthesis. All of these things present additionalchallenges in the study of this problem.The article gives an overview of a number of biological processes of oscillatory nature, as well as mathematical models of these processes. It is noted that the most important factorfor the emergence of cyclic behavior is feedbacks in the system. Based on the analysis of these factors, an algorithm forfinding cyclic modes of functioning of molecular-biologicalsystems is given.The authors declare no conflict of interest.Akinshin A.A., Golubyatnikov V.P. Cycles in symmetric dynamicalsystems. Vestnik NGU = Herald of the Novosibirsk State University.2012;12(2):3-12. 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(in Russian)Zhabotinsky A.M. Concentration Auto-oscillations. Moscow: NaukaPubl., 1974. (in Russian)"} +{"text": "Intraspecific classification of cultivated plants is necessary for the conservation of biological diversity,study of their origin and their phylogeny. The modern cultivated wheat species originated from three wild diploidancestors as a result of several rounds of genome doubling and are represented by di-, tetra- and hexaploid species.The identification of wheat ploidy level is one of the main stages of their taxonomy. Such classification is possiblebased on visual analysis of the wheat spike traits. The aim of this study is to investigate the morphological characteristics of spikes for hexa- and tetraploid wheat species based on the method of high-performance phenotyping.Phenotyping of the quantitative characteristics of the spike of 17 wheat species , includingeight tetraploids and nine hexaploids , T. antiquorum, T. spelta (including cv. Rother Sommer Kolben), T. petropavlovskyi, T. yunnanense,T. macha, T. sphaerococcum, and T. vavilovii), was performed. Wheat spike morphology was described on the basisof nine quantitative traits including shape, size and awns area of the spike. The traits were obtained as a result ofimage analysis using the WERecognizer program. A cluster analysis of plants according to the characteristics of thespike shape and comparison of their distributions in tetraploid and hexaploid species showed a higher variability oftraits in hexaploid species compared to tetraploid ones. At the same time, the species themselves form two clustersin the visual characteristics of the spike. One type is predominantly hexaploid species . The other group includes tetraploid ones . Thus, it has been shown that the morphologicalcharacteristics of spikes for hexaploid and tetraploid wheat species, obtained on the basis of computer analysis ofimages, include differences, which are further used to develop methods for plant classifications by ploidy level andtheir species in an automatic mode. A number of important issues, including aspects of the effective conservation of the biological diversity of cultivatedplant species, the study of their origin, and their phylogeny,presupposes a detailed development of intraspecific classifications . Theproducing of such classifications, reflecting the phylogenesisand genetic structure of species, should be considered themain goal of modern taxonomy . Whendeveloping the classification of cultivated plants, the mostcomplete description of all existing large and small forms(taxons) is assumed . On the one hand, thisis determined, by the convenience of using such a division inexperimental work, on the other hand, it is also determenedin the breeding and testing of cultivated plants. The success and effectiveness of research work is oftenassociated with the detailing and completeness of the experimental study, which depends on what the material is andhow much it should be studied. In this regard, it is extremelyimportant that the natural differentiation of one or anothergenus, the relationship between species, are reflected withhigh accuracy by a detailed taxonomy . Itshould be noted, that for most of the plants important foragriculture, the volumes of the genus and species have notbeen unambiguously described yet . A serious problem in the taxonomy of cultivated plantsis the aspect of taxa agregation vs. fragmentation, and incases of cultivation it manifests itself especially in contrast. At the sametime, the effective use of taxonomy of cultivated plants inthe work of researchers causes certain difficulties. Both dichotomous tables and ideographic manual book requirecertain skills; therefore, the producing of a database andsoftware that allows the identification of species by digitalimages is a very promising direction. The development ofthese methods is mainly based on technologies for analyzing digital images of plant organs within the framework ofcomputer phenomics .Wheat is one of the world\u2019s most important food crops.The modern cultivated wheat species evolved from threewild diploid ancestors as a result of their hybridization andseveral rounds of genome doubling (polyploidization). Currently, cultivated wheat is represented by di- , tetra- and hexaploid species . The main cultivatedspecies, bread wheat (Triticum aestivum L.), is a hexaploid(genomic formula BBAuAuDD). The ploidy level is one ofthe main taxonomic and classifying characteristics of wheatspecies .It can be established by cytogenetic ,molecular methods, as well as by comparing the morphological characteristics of plants . Inthis work, we studied the morphological traits of the plantspikes of tetraploid and hexaploid wheat species based onthe method of high-throughput phenotyping.The aim of the research was to study the distribution ofmorphological traits of spikes of tetra- and hexaploid wheatspecies and compare their distributions.Biological material. We studied 17 polyploid wheat species,namely, nine hexaploids , T. petropavlovskyiUdacz. et Migusch., T. yunnanense King ex S.L. Chen,T. macha Dekapr. et Menabde, T. sphaerococcum Perciv.,T. vavilovii (Thum.) Jakubz.), the near-isogenic line ANK-23 of bread wheat cv. Novosibirskaya 67 and eight tetraploids Schweinf., T. dicoccum (Schrank) Schuebl.,T. durum Desf., T. militinae Zhuk. et Migusch., T. polonicum L., T. timopheevii (Zhuk.) Zhuk., T. turgidum L.); thesample consists of spikes of 595 individual plants, which wasgrown in nine vegetation seasons. The plants were grown in2014\u20132019 in a greenhouse at the Shared Center \u2018Laboratoryof Artificial Plant Cultivation\u2019 of the Institute of Cytologyand Genetics SB RAS. A description of the material usedis given in Table 1.http://db.vir.nw.ru/virdb/maindb)It should be noted that none of the large genebanks of theworld have typical sets of wheat accessions (collections),so them usually reflect either the researchers view on themethods of selection of such sets or aredetermined by the representativeness of the researchersavailable material . Standardtaxonomic descriptions of specimens are given in publiclyavailable databases on genebank websites . The camera is fixed on a stand above the glass. With this method,the front projection of the spike can be captured. Second,the spike is held vertically in front of the blue background.The spike is supported by clip that are placed on a tripod.With this method, by rotating the spike about its axis, fouror more projections of the spike can be captured . According to the protocols, a ColorCheckermust be present in the photographs. It is needed for colournormalisation and scaling. One plant in our dataset can correspond to up to five pictures of its spike taken with differentprotocols and in different projections. Examples of spikesimages (one for each species) are shown in Fig. 1. In total3348 spike images in different projections were captured bythe two protocols, 2097 of them were of hexaploid speciesand 1251 were of tetraploid species. Of these, 915 imageswere obtained using the \u201con the table\u201d protocol and 2433\u201con the clip\u201d.Evaluation of spikes quantitative characteristics.WERecognizer was used to estimatespikes quantitative characteristics based on image analysis.This program describes a wheat spike by geometric modelof two quadrangles based on image analysis . Thegeometry of this model is described by nine independentparameters. The parameters xu1, xu2, yu1, yu2 are for the upper quadrangle; the parameters xb1, xb2, yb1, yb2 are forthe lower quadrangle; the common parameter for the twoquadrangles is the ear length. The program additionallycalculates a number of general features of the shape andsize of the spike, as well as the characteristic of its awning.Details of the feature extraction algorithm are given in.In the present study, we used the model traits that weselected as the most informative for predicting spike densityindex in our previous study , as well asthe general shape and spike trait characteristics. These traitscharacterise a complex view of the morphology (phenotype)of the spike by describing its shape , the physical dimensions of the ear body and the area of the awns (Awns area), thetraits obtained by approximating the ear by two quadranglesare related to the width and length ofindividual segments of the ear (Table 2).Data analysis. In order to estimate the distribution ofspikes in the feature space under study, we used a non-lineart-SNE dimensionality reduction algorithm .This method allows to visualize multidimensional data bymapping objects in multidimensional space to a smaller space. The basic idea behindt-SNE is to reduce the dimensionality of space while maintaining the relative pairwise distances between objects. Theadvantage of the t-SNE method is its tendency to localizeisolated, dense spatial structures of arbitrary geometry. Thet-SNE method was applied to ordinate images of spikes; theimages of each of the projections of a single ear were treatedas separate objects.In order to assess the similarity of the quantitative characteristics of spikes for different species, we used hierarchicalclustering of 17 wheat species accordingto the traits obtained by averaging over all spikes of thesame species. Each species was characterized by a featurevector of length 9. A value of 1\u2013 r was used as a metric forthe distance between species, where r is the value of thePearson correlation coefficient between the values of thetraits . The linkage anddendrogram functions from the SciPy library were used for clustering and dendrogram construction.To compare the variance of traits in plants belongingto different ploidy types, we used F statistics , which evaluates the significance of differences in the variance of two distributions. The data werenormalized by the StandardScaler function of the scikit-learnlibrary . The test was performed independently for each of the nine traits described in Table 2.In this test, one spike image per plant was used, obtained inthe \u201con the table\u201d projection protocol.1.The mean, median, standard deviation and variance of thenine features calculated for the 17 wheat species are presented in the Supplementary 11 Supplementary materials 1\u20134 are available in the online version of the paper: http://vavilov.elpub.ru/jour/manager/files/SupplPronozinA_Engl.pdfLet\u2019s review the distribution of spikes in our sample ofplants according to the characteristic \u201carea of the spikes\u201d.The higher this parameter, the more awns were identifiedfor the spike in the image. According to this characteristic,spikes of hexaploid wheat can be conditionally divided intothree classes: awned , moderatelyawned , and awnless . The species T. compactum, T. spelta,T. petropavlovskyi and T. vavilovii are considered awnedaccording to this criterion. T. aestivum, T. yunnanense,T. macha are moderately awned. The awnless ones are T. antiquorum, i:ANK-23, T. spelta cv. Rother Sommer Kolben,and T. sphaerococcum (see Supplementary 1). These dataagree well with the appearance of the spikes .Thus, representatives of hexaploid wheat show considerablediversity in the presence/absence of awns.If the classification above is applied to tetraploid wheat,only representatives of T. militinae can be assigned to the awnless category.Four species can be classified as moderately awned: T. dicoccoides, T. polonicum, T. timopheevii and T. turgidum. Threespecies are considered awned: T. aethiopicum, T. dicoccum,T. durum. In general, the representation of awned species(specimens) in tetraploid species is significantly higher thanin hexaploid species.Analysis of such characteristic as spike length shows thatspikes can also be divided into three classes: length less than60 mm (short), from 60 to 90 mm (medium) and more than90 mm (long). According to this classification, the hexaploid wheat species T. spelta, T. petropavlovskyi and T. vaviloviican be classified as long spikes, T. aestivum, T. yunnanense,T. spelta cv. Rother Sommer Kolben and T. macha to mediumspikes, and T. compactum, T. antiquorum, T. sphaerococcumand the near-isogenic lineage ANK-23 to short spikes. Theboundary between species characterized by long and medium spikes is rather conditional. For tetraploid species wedid not find any species which according to this parameterwould fall into the category of long-boned. The mediumsized category could include T. aethiopicum, T. dicoccoides,T. polonicum, T. turgidum, the short spike category \u2013 T. dicoccum, T. durum, T. timopheevii and T. militinae.The spike length distribution of the samples studiedfor hexaploid and tetraploid species is shown in Fig. 3, a.The Fig. 3, b shows the distribution of the parameter alsocharacterizing the size of the spikes \u2013 the perimeter of thecontour of the body of the spike in the image.Fig. 3 shows that the distributions of both parameters inhexaploid wheat are more scattered, while the variability ofthese traits in hexaploid wheat is higher mainly due to thehigher frequency of occurrence of ears with high values ofthese traits. The distribution of the analyzed ears images in the spaceof nine features was visualized using the t-SNE method,resulting in a two-dimensional parameter space (components 1 and 2). The results of the transformation are shownin Fig. 4. In the resulting diagram, each point represents oneof the analysed images of the spike. In Fig. 4, a the dots arecoloured according to the type of ploidy of the plant . In Fig. 4, b the colour and shape of eachdot corresponds to a particular wheat spike image.The diagram in Fig. 4, a shows that the areas occupiedby hexa- and tetraploid wheat species strongly overlap onthe graph. This means that the spikes of these two groupsare quite similar in their characteristics. This is consistentwith the results presented in the Supplementaries 1 and 2as well as in Fig. 3. However, it should be noted that in thediagram in Fig. 4, a samples of hexaploid species occupya larger area, primarily due to the predominance of thecorresponding points in the right part of the diagram. Onecan see that orange dots (hexaploid wheat) predominate inthe area with values of component 1 more than \u201320, thispredominance is even more pronounced in the upper rightcorner of the diagram . This means that a numberof spike trait characteristics have some values for hexaploidspecies specific only, but not for tetraploid ones. This agreeswell with the result shown in Fig. 3. In particular, such areasmay correspond to large values of the parameters \u201cperimeter\u201d and \u201cear length\u201d.The diagram in Fig. 4, b shows that the areas occupied bysamples of the different species overlap considerably. Forexample, T. aestivum and T. durum species overlap across theentire plot area (dotted line). At the same time, it should benoted that the images of spikes belonging to the same wheatspecies occupy mostly compact areas on the graph. At thesame time, there are species for which the spike samples aredivided into several clearly visible clusters according to theircharacteristics. Such species include T. compactum and T. petropavlovskyi .Fig. 1 shows that hexaploids are represented by plants withtwo characteristic types of spikes: long and thin ; short and rounded . In Fig. 4. b the group of plants with short androunded spikes is located in the component 2 value rangefrom \u201380 to 0 (lower part of the graph). Plants with longand thin spikes have component 2 values between 0 and 80(upper part of graph). In Fig. 4, a, these two groups of plantscorrespond roughly to the two clouds of dots in hexaploid wheat at the top and bottom of the graph, which overlapslightly in the central part of the graph. Thus, the diagramsin Fig. 4 provide a clear indication of the diversity of spikesin their characteristics within and between species. To characterize in more detail the similarity of morphometric characteristics of spikes in different wheat species, weconducted a hierarchical cluster analysis for them based on acomparison of the mean values of the studied traits. Fig. 5 shows that the wheat species were divided intotwo clusters (highlighted in red and green). The first cluster(red) predominantly includes tetraploid species . However, wildtetraploid wheat species T. diccocoides is not included inthis cluster, while among hexaploid species, T. compactum,T. antiquorum and T. sphaerococcum differing from all otherspecies by compact spike shape, i. e. having the shortestspike of all studied hexaploid wheat species are includedin it. It should be noted that in the work of A. Zatybekovet al. (2020), using economically important traits, samplesof six tetraploid species were clustered arbitrarily, i. e. irrespective of their species identity. It is important to note,that remaining hexaploid species were clearly divided byspike length into two clusters of medium and long spikes . T. spelta and T. spelta cv. Rother Sommer Kolben (a German landrace) occur in the same cluster. This allows us toconclude that the \u201cspecies\u201d shape of spike during long-termwheat breeding did not change for a long time and may be successfully used forclassification of the species.It should be noted that the only wild tetraploid loosespike species in the genus, T. dicoccoides, has fallen to thehexaploids. While hexaploid wheat species with compactear type \u2013 T. compactum, T. antiquorum, T. sphaerococcumand human-made near-isogenic line ANK-23 of spring breadwheat cv. Novosibirskaya 67 \u2013 were includedinto tetraploid species. The latter leads to the conclusion thatalthough near-isogenic lines are produced on a particular(specific) species, nevertheless, their species identity shouldbe treated with caution.Let\u2019s take a look at T. petropavlovskyi. The species wasfounded at the Chinese Pamir \u2013 route of the Great silkroad. According to the results of the study of gliadins, allaccessions of this species were very similar to such hybridcombination obtained from crossing bread wheat withT. polonicum . The authors of the\u201cCultural Flora of the USSR\u201d also considered a possiblehybrid origin of this species . In addition, T. petropavlovskyi also resembles bread wheat in anumber of taxonomic traits . Previously,R.L. Boguslavsky (1982) described hybrids from crossing T. aestivum with T. polonicum produced by CIMMYTbreeders as subspecies of T. petropavlovskyi ssp. mexicanaBogusl. Based on the above, we considered it appropriate toconbided T. petropavlovskyi as the subspecies of T. aestivum:Triticum aestivum ssp. petropavlovskyi comb. et stat.nov. (Udacz. et Migusch.) N.P. Gontsch. \u2013 T. turanicumJakubz. convar. montanostepposum Jakubz. f. aristiformeJakubz. 1959. Bot. Zhur. 10:1428, nom. illig. \u2013 T. petropavlovskyi Udacz. et Migusch. 1970. Vestn. Sel\u2019skokhoz.Nauki. 9:20.Typus: described by an accession from China \u201cOrigin:China, Xinjiang Province, village Kurlia, K-48376,1957. A.M. Gorsky exp[edition]. Reproduction ofCentral Asia, Tashkent, Central Asian Station of VIR.08. VII. 1969, Collected/defined: R.A. Udachin &E.F. Migushova\u201d in St. Petersburg (WIR!). (The herbarium specimens of the type and paratype of Triticumaestivum ssp. petropavlovskyi are given in the Supplementaries 3 and 4).Note that the results presented in Fig. 3 and 4, a show thathexaploid species have a greater variability in spike shape,size and awnness characteristics. Therefore, we hypothesizedthat the spike trait characteristics of hexaploid species mayhave a higher variation than those of tetraploid species. Totest this assumption, we compared the variance of the estimated parameters using an F-distribution (Table 3).The results presented in Table 3 show that the variance ofmost of the characters for hexaploids and tetraploids havesignificant differences (\u200ap < 0.05). At the same time, thesignificant differences in variance were not found for suchtraits as ybm (quadrangle model parameter), Awns area andCircularity index. It is interesting to note that for all significant differences, we observe a higher variance in hexaploidsthan in tetraploids. Thus, the analysis showed that hexaploidspecies show higher diversity in spike morphometric traitcharacteristics compared to tetraploid species.The data represent plants of 17 wheat species: 9 hexaploids , T. petropavlovskyi, i:ANK-23 (near-isogenic line of bread wheat cv.Novosibirskaya 67), T. yunnanense, T. macha, T. sphaerococcum, T. vavilovii) and 8 tetraploids . The results of their clusteringare presented so that the colour and shape of each dot corresponds to a particular species .It is well known that genome doubling as a result of duplications (autopoploidy) or hybridization and subsequentpolyploidization leads to marked changes inplant phenotype . These changes in plants occurboth at the cellular level and at the organlevel . In many cases, in plants, anincrease in ploidy leads to an increase in cell and organsize , increasingresistance to stress . Currently, researcherssuggest that there are four types of molecular mechanismsof such variability: 1) increased gene/allele dosage, 2) increased genetic diversity, 3) altered genetic regulation, and4) epigenetic rearrangements of the genome . The analysis of morphological characteristics of spikesof hexaploid (2n = 6x = 42) and tetraploid (2n = 4x = 28)wheat has shown, that most of spike characteristics havesignificantly higher variation in wheat with higher spikeploidy. Our results are in agreement with the ideas about theinfluence of ploidy on plant phenotype variability.A large-scale analysis of the spike digital images of595 plants of 8 tetra- and 9 hexaploid wheat species wascarried out. Nine quantitative traits describing the shape,size and awnedness of the spike were studied. The variabilityamong the above genotypes was studied and it was shownthat two clusters are formed in the spike characteristic space.The first cluster includes mainly hexaploid species (withthe exception of wild tetraploid species T. dicoccoides).The second cluster includes tetraploid species . Analysis of variance of these characters inhexaploid and tetraploid wheats showed a significant in crease in variance for six of nine characters in the sample ofhexaploids, i. e. greater ploidy level gives more variabilityin quantitative characters of spike morphologyThus, it is shown that morphological trait characteristicsof spikes of hexa- and tetraploid species, obtained on thebasis of computer image analysis, demonstrate the differences, which can be used in the future to develop a methodof classification of plants by ploidy level and their speciesaffiliation in automatic mode.The authors declare no conflict of interest.Afonnikov D.A., Genaev M.A., Doroshkov A.V., Komyshev E.G.,Pshenichnikova T.A. Methods of high-throughput plant phenotyping for large-scale breeding and genetic experiments. Russ. J. Genet.2016;52(7):688-701. DOI 10.1134/S1022795416070024.Boguslavsky R.L. A new botanical form of hexaploid wheat. 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(inRussian)Dorofeev V.F., Filatenko A.A., Migushova E.F., Udachin R.A., Yakubtsiner M.M. Flora of Cultivated Plants of USSR. Vol. 1. Wheat. Leningrad: Kolos Publ., 1979. (in Russian)Dorofeev V.F., Rudenko M.I., Filatenko A.A., Baras J., Segnalova J.,Lemann H. (Compilators). \u0422h\u0435 Int\u0435rn\u0430ti\u043en\u0430l \u0421\u043em\u0435\u0441\u043en List \u043ef D\u0435s\u0441ri\u0440t\u043ers for the G\u0435nus \u0422riti\u0441um L. Leningrad: VIR Publ., 1984. (inRussian)Finigan P., Tanurdzic M., Martienssen R.A. Origins of novel phenotypic variation in polyploids. In: Polyploidy and Genome Evolution.Berlin; Heidelberg: Springer Press, 2012;57-76. DOI 10.1007/978-3-642-31442-1_4.Genaev M.A., Komyshev E.G., Fu Hao, Koval V.S., Goncharov N.P.,Afonnikov D.A. SpikeDroidDB: an information system for annotation of morphometric characteristics of wheat spike. VavilovskiiZhurnal Genetiki i Selektsii = Vavilov Journal of Genetics andBreeding. 2018;22(1):132-140. DOI 10.18699/VJ18.340. (in Russian)Genaev M.A., Komyshev E.G., Smirnov N.V., Kruchinina Y.V., Goncharov N.P., Afonnikov D.A. Morphometry of the wheat spike byanalyzing 2D images. Agronomy. 2019;9(7):390. DOI 10.3390/agronomy9070390.Golovnina K.A., Kondratenko E.Ya., Blinov A.G., Goncharov N.P.Phylogeny of the A genome of wild and cultivated wheat species.Russ. J. Genet. 2009;45(11):1360-1367. DOI 10.1134/S1022795409110106.Goncharov N.P. Comparative-genetic analysis \u2013 a base for wheat taxonomy revision. Czech J. Genet. Plant Breed. 2005;41:52-55.Goncharov N.P. Manual Book of Common and Hard Wheat Varieties.Novosibirsk: SO RAN Publ., 2009. (in Russian)Goncharov N.P. Genus Triticum L. taxonomy: the present and the future. Plant Syst. Evol. 2011;295(1-4):1-11. DOI 10.1007/s00606-011-0480-9.Goncharov N.P., Kondratenko E.Ya. Wheat origin, domestication andevolution. Informatsionnyy Vestnik VOGiS = The Herald of VavilovSociety for Geneticists and Breeders. 2008;12(1/2):159-179. (inRussian)Goncharov N.P., Shumny V.K. From preservation of genetic collectionsto organization of National project of plant gene pools conservation in permafrost. Informatsionnyy Vestnik VOGiS = The Herald ofVavilov Society for Geneticists and Breeders. 2008;12(4):509-523.(in Russian)Hammer K., Filatenko A.A., Pistrick K. Taxonomic remarks on Triticum L. and \u00d7Triticosecale Wittm. Genet. Resour. Crop Evol. 2011;58(1):3-10. DOI 10.1007/s10722-010-9590-4.Johnson S.C. Hierarchical clustering schemes. Psychometrika. 1967;32(3):241-254.Koval S.F. The catalog of near-isogenic lines of Novosibirskaya-67common wheat and principles of their use in experiments. Russ. J.Genet. 1997;33(8):995-1000.Liu W., Zheng Y., Song S., Huo B., Li D., Wang J. In vitro induction ofallohexaploid and resulting phenotypic variation in Populus. PlantCell Tiss. Organ Cult. 2018;134(2):183-192. DOI 10.1007/s11240-018-1411-z.M\u00fcllner D. Modern hierarchical, agglomerative clustering algorithms.arXiv. 2011;1109.2378.Palmova E.F. Introduction to Wheat Ecology. Moscow; Leningrad:Selkhozgiz Publ., 1935. (in Russian)Pedregosa F., Varoquaux G., Gramfort A., Michel V., Thirion B.,Grisel O., Blondel M., M\u00fcller A., Nothman J., Louppe G., Prettenhofer P., Weiss R., Dubourg V., Vanderplas J., Passos A., Cournapeau D., Brucher M., Perrot M., Duchesnay E. Scikit-learn: Machinelearning in Python. J. Mach. Learn. Res. 2011;12:2825-2830.Robinson D.O., Coate J.E., Singh A., Hong L., Bush M., Doyle J.J.,Roeder A.H. Ploidy and size at multiple scales in the Arabidopsis sepal. Plant Cell. 2018;30(10):2308-2329. DOI 10.1105/tpc.18.00344.Rodionov A.V., Amosova A.V., Belyakov E.A., Zhurbenko P.M., Mikhailova Y.V., Punina E.O., Shneyer V.S., Loskutov I.G., Muravenko O.V. Genetic consequences of interspecific hybridization, its rolein speciation and phenotypic diversity of plants. Russ. J. Genet.2019;55(3):278-294. DOI 10.1134/S1022795419030141.Rodionov A.V., Shneyer V.S., Gnutikov A.A., Nosov N.N., Punina E.O.,Zhurbenko P.M., Loskutov I.G., Muravenko O.V. Species dialectics:from initial uniformity, through the greatest possible diversity to ultimate uniformity. Botanicheskiy Zhurnal = Botanical Journal. 2020;105(9):835-853. DOI 10.31857/S0006813620070091. (in Russian)Romanov B.V., Pimonov K.I. Phenomogenomics of Production Traitsof Wheat Species. Persianovsky: Donskoy GAU Publ., 2018. (inRussian)Sinskaya E.N. Historical Geography of Cultural Flora (At the Dawn ofAgriculture). Leningrad: Kolos Publ., 1969. (in Russian)Snedecor G.W., Cochran W.G. Statistical Methods. Ames, Iowa: IowaState University Press, 1989.Tan F., Tu H., Liang W., Long J.M., Wu X.M., Zhang H.Y., Guo W.W.Comparative metabolic and transcriptional analysis of a doubleddiploid and its diploid citrus rootstock (C. junos cv. Ziyang xiangcheng) suggests its potential value for stress resistance improvement.BMC Plant Biol. 2015;15:89. DOI 10.1186/s12870-015-0450-4.Udachin R.A., Migushova E.F. New in the knowledge of the genusTriticum. Vestnik Selskokhozyaystvennoy Nauki = Herald of Agricultural Sciences. 1970;9:20-24. (in Russian)van der Maaten L., Hinton G. Visualizing data using t-SNE. J. Mach.Learn. Res. 2008;9:2579-2605.van Slageren M., Payne T. Concepts and nomenclature of the Farrowheats, with special reference to Emmer, Triticum turgidum subsp. dicoccum (Poaceae). Kew Bull. 2013;68:477-494. DOI 10.1007/S12225-013-9459-8.Virtanen P., Gommers R., Oliphant T.E., Haberland M., Reddy T., Cournapeau D., Burovski E., Peterson P., Weckesser W., Bright J., van derWalt S.J., Brett M., Jones E., Kern R., Larson E., Carey C.J., Polat I.,Feng Yu, Moore E.W., VanderPlas J., Laxalde D., Perktold J., Cimrman R., Henriksen I., Quintero E.A., Harris C.R., Archibald A.M.,Riberio A.H., Pedregosa F., van Mulbregt P. SciPy 1.0 Contributors. SciPy 1.0 \u2013 fundamental algorithms for scientific computing inPython. Nat. Meth. 2020;17(3):261-272. DOI 10.1038/s41592-019-0686-2.Watanabe N., Bannikova S.V., Goncharov N.P. Inheritance and chromosomal location of the genes for long glume phenotype found inPortuguese landraces of hexaploid wheat, \u2018Arrancada\u2019. J. Genet.Breed. 2004;58:273-278.Williams J.H., Oliveira P.E. For things to stay the same, things mustchange: polyploidy and pollen tube growth rates. Ann. Bot. 2020;125(6):925-935. DOI 10.1093/aob/mcaa007.Yakubtsiner M.M. More on Chinese wheats. Botanicheskiy Zhurnal =Botanical Journal. 1959;44(10):1425-1436. (in Russian)Yang W., Feng H., Zhang X., Zhang J., Doonan J.H., Batchelor W.D.,Xiong L., Yan J. Crop phenomics and high-throughput phenotyping: past decades, current challenges, and future perspectives. Mol.Plant. 2020;13(2):187-214. DOI 10.1016/j.molp.2020.01.008.Zatybekov A., Anuarbek S., Abugalieva S., Turuspekov Y. Phenotypicand genetic variability of a tetraploid wheat collection grown in Kazakhstan. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2020;24(6):605-612. DOI 10.18699/VJ20.654.Zhang Y., Zhao C., Du J., Guo X., Wen W., Gu S., Wang J., Fan J. Cropphenomics: current status and perspectives. Front. Plant Sci. 2019;10:714. DOI 10.3389/fpls.2019.00714.Zuev E.V., Amri A., Brykova A.N., Pyukkenen V.P., Mitrofanova O.P.Atlas of the Diversity of Soft Wheat (Triticum aestivum L.) by Earand Grain Characteristics. St. Petersburg: Kopi-R Publ., 2019. (inRussian)"} +{"text": "The Department of Wheat Genetic Resources of the All-Russian Research Institute of Plant GeneticResources (VIR) had developed and published in 1979 a classification of the genus Triticum L., which is based onthe genomic composition of species and the presence or absence of a number of main genes that govern the\u201cclassification\u201d traits. The grounds have been laid by F. K\u00f6rnicke and J. Percival, and supplemented by N.I. Vavilovand K.A. Flaksberger. The classification, which is most often referred to as the \u201cClassification of Triticum by Dorofeev et al.\u201d, belongs to a number of the main modern classifications of the genus. This is the world\u2019s first standardized system that contains all known intraspecific (infraspecific) taxa of wild and cultivated wheat species.A detailed classification makes it possible to identify a wide variety of forms in the genus Triticum L. and itsindividual species, which is especially important for collections preserved in genetic seed banks. The use of theintraspecific classification of the genus Triticum L. greatly simplifies the identification of the VIR collection accessions introduced from various sources or checking accession identity after regeneration in the field. However,the direct use of such a voluminous classification meets several difficulties. Therefore, we propose a unifiedintraspecific classification of durum wheat, based on the description of only 16 main botanical varieties outof 131 described so far, which have complexes of morphological traits of the spike and kernel that occur mostfrequently in durum wheat collections. The remaining 115 botanical varieties, which have additional traits, gettheir name by the addition of the abbreviated Latin name of one or another additional trait to the main name.Having mastered this way of describing the morphological traits of accessions, any user can easily navigateoneself in the systematized intraspecific diversity of collections. The purpose of this work is to acquaint thereader with the intraspecific classification of durum wheat (Triticum durum Desf.) developed at VIR and to offerits simplified version, which is based on the identification of the main and additional morphological traits of thespike and kernel. Durum wheat (Triticum durum Desf.) is characterized by awide diversity of varieties and forms. Like any set, this diversity should be systematized to better understand the relationships between its constituent units. Classification isa method aimed at organizing a system of subordinate groups,in which these units are combined on the basis of similarityin certain essential properties . The productof the classification is a system. Plant systematics is a branchof botany that deals with the classification of plants. The term\u201csystematic\u201d (systematic botany) was introduced by the Swedish naturalist Carl von Linn\u00e9 in 1751 in his work \u201cPhilosophyof Botany\u201d . The term \u201ctaxonomy\u201d was introduced by the Swiss botanist Augustin Pyrame de Candolle,the creator of the natural system of plants classification \u2013 thede Candolle system \u2013 and designated the theory of plant classification, according to the rules of which taxa are arranged inthe system . In his treatise \u201cOn the Originof Species\u2026\u201d, the English naturalist Charles Robert Darwinconsidered the terms taxonomy and systematic as synonyms. However, systematics studies not only thediversity of organisms, but also the causes and ways of itsappearance, and includes taxonomy and nomenclature.The history of the genus Triticum L. classification beginswith C. Linnaeus , who is considered bymost triticologists as the author of the genus Wheat. Over300 years of its existence, the Linnaeus classification has undergone numerous interpretations, which are associated withthe inclusion or subsequent exclusion of certain cultivatedand wild species from it.The system of the genus Triticum L. developed at the Department of Wheat Genetic Resources of Federal ResearchCenter the N.I. Vavilov All-Russian Institute of Plant GeneticResources (VIR) , was built up onthe research of such triticologists as F. K\u00f6rnicke (1885) andJ. Percival (1921), and further revised and supplemented byN.I. Vavilov (1935) and K.A. Flaksberger . The system is based on taking intoaccount the genomic composition of species and the presenceor absence of a number of major genes that govern systematically important traits.In accordance with this system of the genus, durum wheat(T. durum Desf.) is treated as a separate species in the rank ofthe species, which was first described by the French botanistR.L. Desfontaines (1798). The species includes two subspecies: subsp. durum and subsp. horanicum Vav. The latter isa subspecies of the most dense-ear wheats, with a complexof specific morphological characters. Subsp. durum is a subspecies of durum wheat proper, within which six groups ofbotanical varieties (convarieties) are distinguished, namelyconvar. durum, durocompactum Flaksb., aglossicon Dorof.et A. Filat., villosum (Jakubz.) Dorof. et A. Filat., falcatum(Jakubz.) Dorof. et A. Filat., caucasicum (Dorof.) Dorof. Inturn, convar. durum includes three subconvarieties: subconvar.durum, muticum (Orlov) Dorof. et A. Filat., and duroramosum Dorof. (Table 1). At the time of the creation of the classification by V.F. Dorofeev et al. (1979), the genus T. durumDesf. numbered 120 botanical varieties and 29 forms in20 varieties. As a result of subsequent studies, 11 more botanical varieties and 12 forms were identified .1, purple grain of T. aethiopicum Jakubz. , and ear branching in T. turgidum L. . At the same time, the botanical varieties identified byus have a simple control of characters. For example, ligulessness or awnlessness.The classification, which is most often referred to as theClassification of Triticum by Dorofeev et al., belongs toa number of the main modern classifications of the genusTriticum L. This was the first standardized classification thatcontained all known intraspecific taxa of wild and cultivatedwheat species. A similar classification, a development of previous classifications based on the use of a comparative geneticapproach, was proposed by N.P. Goncharov . In contrast to hexaploidwheats, the species classification of which can be constructedusing only five main genes , in tetraploidspecies only Polish wheats and Ispahan emmer wheat can differ oligogenically . Inall other species, only a part of taxonomically important traitshas simple genetic control. This refers, e.g., to tetra-awnednessin the majority of T. carthlicum Nevski varieties The gene has been recently introgressed into hexaploid wheat and mapped .Such a detailed classification makes it possible to identifya wide diversity when working with the genus Triticum L. asa whole and/or with its individual species, which is especially important for large-scale collections preserved in geneticseed banks.The use of intraspecific classification of the genus Triticum L. greatly simplifies the identification of the VIR collection accessions introduced from various sources, or whenchecking accession identity after regeneration in the field.However, apart from the researchers at the Department ofWheat Genetic Resources of VIR, few people use this approach in their practical work, and there are several reasonsfor this. First, both the monograph itself and the accompanying \u201cIdentifier of Wheat\u201d have not been reprinted for more than 40 yearsand became a bibliographic rarity, which makes it difficultfor national breeders and other wheat researchers to use it. After the collapse of the USSR, the geneticbanks of the COMECON countries stopped working according to a common pattern, although many of them continueto use the system developed by V.F. Dorofeev et al. (1979).Second, there is still no translation of these works into English,although there was an international project on the translationof this monograph , which makes itimpossible for the staff of foreign genetic seed banks to getacquainted with this classification. Third, only the long-termpractice of identifying accessions by the name of a botanicalvariety makes it possible to carry out this laborious workpromptly and without difficulty. For instance, durum wheatalone requires remembering names of 131 varieties and theirmeaning. One of the ways to reduce the number of hard-toremember names may be unification as a standardizationmethod aimed at reducing the number of objects by combiningseveral characters. It assumes selection of the optimal numberof objects, botanical varieties in our case, limited to a reasonable minimum and leads to a certain uniformity. This greatlysimplifies the practical use of the classification. The objective of this work is to acquaint the reader withthe intraspecific classification of durum wheat (Triticum durum Desf.) developed at VIR, and to offer its simplified analogbased on the identification and illustration of the main andadditional morphological characters of the ear and kernel.Here, we propose a unified intraspecific classification of thedurum wheat species, based on the description of only 16 mainbotanical varieties which have the most commonly occurringsets of morphological characters of the ear and kernel, and retain their author\u2019s name (Table 2). The remaining botanicalvarieties, which have additional characters, get their name bythe addition of this or that additional character to the mainabbreviated Latin name (Table 3). Such a way of describingand quickly memorizing intraspecific diversity was proposedfor common wheat in . This work has beensuccessfully published twice and is in great demand bothdomestically and among employees of foreign genetic seedbanks.Basic and additional morphological charactersof durum wheatThe intraspecific description system is based on botanicalvarieties, the names of which are determined by a set ofmorphological characters of the ear and kernel. These setswere distinguished by a combination of such features asthe presence or absence of glume pubescence, glume color , the presenceor absence of awns on the lemma, theircolor , and the kernel shape and color (see Table 2).A description of each botanical variety must include a set of main features: thepresence/absence of glume pubescence, the color of the glume and kernel, the presence/absence of awns on the lemma, and the color of awns. The set of charactersrevealed by a specimen is designated by the corresponding Latin name given bythe author (see Table 3).To describe a specimen that possesses one of these sets of characters, but incombination with an additional character, like color of the glume, different length ofawns, their color, etc., abbreviated Latin names of these characters are used (Table 4).In the case of durum wheat, these names are added to the name of the main set inthe case of peduncle pubescence (piloso-) or awns smoothness (levi-), or when theydetermine the names of groups or subgroups of botanical varieties, i. e., dense-eared(-compactus); with the crescent-shaped kernel ; with the branching ear(ramoso-), non-ligulate (quasi-), with the densely pubescent leaf blade and sheathof the leaf, and with the hard glume (villoso-). Along with the characters of the earand kernel, Table 4 contains that of the ligula absence, which is the only characterof the leaf taken into account when describing botanical varieties.Unified intraspecific classificationof durum wheat (Triticum durum Desf.)2.The proposed unified intraspecific classification is a simplifiedanalog of the durum wheat key . Thewhole diversity is arranged in the form of tables, where thenames of varieties according to K.A. Flaksberger (1935) andV.F. Dorofeev et al. (1979) are given for comparison, whichallows a user to establish a correspondence between the formbeing described and the botanical variety. The botanical varieties are presented in accordance with the main charactersin the following sequence: the awned and awnless forms arepresented in Table 5 and Supplementary2 Supplementary material is available at: http://vavilov.elpub.ru/jour/manager/files/Suppl_Lyapunova_Engl.pdfIn the first place, these tables present botanical varietieswith non-pubescent glumes and different color combinationsof the glume and kernel, and then those with the pubescentglumes in the same order.Glabrous glumeWhite spike, white kernel.Red spike, white kernel.White spike, red kernel. Red spike, red kernel.White spike, purple kernel.Red spike, purple kernel.Pubescent glume: White spike, white kernel.Red spike, white kernel. White spike, red kernel.Red spike, red kernel.All of the above main characters have simple genetic control.Acquaintance with the durum wheat intraspecific classification, which was created at VIR and contained all the knownintraspecific taxa of the time as well as the subsequently addedones, will make it possible to analyze all the intraspecificdiversity of the main cultivated tetraploid species Triticumdurum Desf. The proposed simplified analog version, basedon the identification of the main and additional morphologicalcharacters of the ear and kernel, can help any user simplifythe systematization of the intraspecific diversity contained inany collection and easily navigate it.The authors declare no conflict of interest.Barulina E.N. Comparative genetic study of Triticum species: I. Genetics of the ligula trait in different chromosomal wheat species:T. vulgare Vill., T. compactum Host, T. durum Desf. 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DOI 10.1007/BF00021076.Zuev E.V., Amri A., Brykova A.N., Pyukkenen V.P., Mitrofanova O.P.Atlas of Bread Wheat (Triticum aestivum L.) Genetic DiversityBased on Spike and Kernel Characters. 2nd ed. St. Petersburg:Kopi-R Publ., 2019. (in Russian)"} +{"text": "In the mid-20th century, the first case of infection of European bees Apis mellifera L. with the ectoparasite mite Varroa destructor was recorded. The original host of this mite is the Asian bee Apis cerana. Themite V. destructor was widespread throughout Europe, North and South America, and Australia remained theonly continent free from this parasite. Without acaricide treatment any honeybee colony dies within 1\u20134 years.The use of synthetic acaricides has not justified itself \u2013 they make beekeeping products unsuitable and mitesdevelop resistance to them, which forces the use of even greater concentrations that can be toxic to the bees.Therefore, the only safe measure to combat the mite is the use of biological control methods. One of thesemethods is the selection of bee colonies with natural mite resistance. In this article we summarize publicationsdevoted to the search for genetic markers associated with resistance to V. destructor. The first part discussesthe basic mechanisms of bee resistance (Varroa sensitive hygienic behavior and grooming) and methods fortheir assessment. The second part focuses on research aimed at searching for loci and candidate genes associated with resistance to varroosis by mapping quantitative traits loci and genome-wide association studies.The third part summarizes studies of the transcriptome profile of Varroa resistant bees. The last part discussesthe most likely candidate genes \u2013 potential markers for breeding Varroa resistant bees. Resistance to the miteis manifested in a variety of phenotypes and is under polygenic control. The establishing of gene pathwaysinvolved in resistance to Varroa will help create a methodological basis for the selection of Varroa resistanthoneybee colonies. The Varroa destructor Anderson & Trueman, 2000 is the mostwidespread and most harmful pest of bees . Review articles devoted toV. destructor deal with various aspects of its biology , ways to mite control , issues of bee resistance to mite and hygienic behavior .The invasion of Varroa has become a challenge for theEuropean bee, since it has not developed the natural defensemechanisms that well developed in the original host of themite \u2013 the Asian bee Apis cerana. The resistance of the Asianbee to the mite is due to the fact that it has well-developedbehavioral defense mechanisms and the mite parasitizesmainly on drone brood . The currently knownmethods of fighting V. destructor are based on the use of synthetic acaricides and biological control methods . Theproblem of acaricides accumulation in beekeeping productsand the development of acaricides resistance in the mite makebeekeepers refuse to use them. Therefore, biological controlmethods are of great importance, one of which is the selectionof bees that have resistance toward the Varroa mites.The purpose of this review is to summarize the materialsof experimental studies devoted to the establishment of thegenetic basis of honey bee resistance to the V. destructor.There are two main phenotypes associated with resistance tomite: Varroa sensitive hygiene behavior and grooming, whichincludes auto-grooming (self-cleaning) and allogrooming(cleaning the body of another member of colony).Before considering the concept of Varroa sensitive hygienic behavior, let\u2019s get acquainted with such a mechanismof protecting bees from brood diseases as hygienic behavior.In 1964 the brood removal behavior of bees infected withAmerican foulbrood was described . Thisbehavior, called hygienic, consisted of the following actions \u2013detecting, uncapping and removing the infected brood. Abouttwenty years later, Gilliam et al. (1983) showed that hygienicbehavior is also effective against ascospherosis. In 1993, thebreeding program for honey bee colonies with a high level ofhygienic behavior has been started in the University of Minnesota . It was found that hygienic behavior isperformed by 15\u201317 days old bees . Beesremove fifth instar larvae infected with the bacterium Paenibacillus larvae (caused American foulbrood) and the fungusAscosphaera apis (causative agent of ascospherosis) before the pathogens reach the sporulation stage .In 1997, the Suppression of Mite Reproduction (SMR)phenomenon was described: bee colonies with this phenotypehave a low number of reproductively successful female mites. It soon became clear that SMR is aconsequence of specific hygienic behavior aimed at removinga mite, which has offspring. It is known that the foundressmite, after penetrating into an unsealed cell with a bee larva,begins to lay eggs only 3 days after the cell is sealed . The detection and removal of thecells content with mite offspring leads to a reduction in thetotal number of mites in the bee colony. This type of behavior has been termed Varroa sensitive hygiene (VSH) .To assess hygienic behavior, two tests have been developedand are widely used, \u2013 freeze-killed brood assay, FKB and pin-killed brood assay, PKB. These tests are often used in experimental studies to analyze resistance toward the Varroa mite,so we will consider a short protocol for their implementation.The brood combs are frozen (FKB) or killed with a pin (PKB)and introduced into the test colony for 24 hours. If colonyremoves more than 95 % of the killed brood it is consideredhighly hygienic. VSH assessment is more complex: a sectionof combs with sealed brood infested with mites is introducedinto the test colony and after a week the percentage of uncapped and cleaned cells and other indicators are calculated. FKBassay was developed to assess hygienebehavior, however Danka et al. (2013) reported that coloniesbred for VSH remove frozen brood faster (in 6\u201312 hours)than colonies bred for FKB assay. At the same time, coloniesselected using FKB assay do not cope with the test developedto assess VSH phenotype. Therefore, FKB assay can be usedto test VSH phenotype, but this fact requires additional verification.Grooming behavior is another natural defense mechanism ofbees, which consists in the ability of bees to clean themselves(auto-grooming) or other bees from externalparasites and pollution . It is strongly expressed in A. cerana . This is especially true for allogrooming: if an Asianbee cannot remove a mite by itself, it performs a special dancethat provokes other bees to perform allogrooming . There are also a difference in grooming betweenA. mellifera subspecies. For example, Africanized bees removemites more intensively than European subspecies . Colonies are assessed for this feature both atthe individual and colony level .In addition, populations of A. mellifera were identified thatsurvived and coexist with V. destructor for a long time. Evaluation of such colonies showed that they have a high level ofVarroa sensitive and grooming behavior . Onthe basis of genomic and transcriptome studies, loci and genesassociated with Varroa resistance were identified.Oxley et al. (2010) identified the Hyg1 locus on chromosome 2associated with hygienic behavior. The 95 % confidence interval of this locus included genesassociated with behavior, smell, development and functioningof neurons, receptor and transcriptional activity. Harpur et al.(2019) based on genome-wide sequencing of drones from twoapiaries selected for hygienic behavior and one non-selectedapiary identified 73 candidate genes. 49 of them were locatednear previously identified loci . Of great interest are the abscam, goosecoid (Hoxgene) and tropomysin-2-like genes on chromosome 6, theortholog of the Drosophila dyschronic gene (GB45054) onchromosome 11, and the insulin-like receptor (GB53353) onchromosome 9. Abscam is known to play an important rolein axonal guidance, in particular of olfactory neurons. Thegoosecoid and tropomysin-2-like genes are also essentialfor the development of the nervous system. The GB45054gene is involved in biological processes such as sensoryperception of sounds and light stimuli. GB53353 is involvedin protein phosphorylation and the transmembrane receptorprotein tyrosine kinase signaling pathway. Kim et al. (2019)performed genome-wide sequencing of A. m. caucasica withhigh hygienic behavior and A. m. carnica with a low level ofhygiene. They obtained 20 SNP markers associated with hygienic behavior, and candidate genes were identified for threeof them. SNP1 is located in the twitchin (chromosome 2), in thepreviously identified locus Hyg1 . SNP8and SNP9 are located in the gene encoding a peroxidase-likeprotein (chromosome 4)In studies hygiene behavior was assessed using FKB assay,and, as it was said, colonies selected on FKB do not alwayssuccessfully cope with a mite. However, given that Varroasensitive and general hygienic behavior are based on the samemechanism (detecting and uncapping diseased brood), resultsobtained by these authors should not be excluded from furtherconsideration.Genome-wide analysis of VSH was carried out by researchgroups from the USA and Germany. Tsuruda et al. (2012) identified alocus on chromosome 9 associated with VSH phenotype. Thislocus contains the NorpA2 gene (homologue of the D. melanogaster NorpA) and the dopamine receptor Dop3. NorpA2,encoding phospholipase C, is associated with learning andmemory formation in the honey bee .Whereas dopamine plays a critical role in the formation ofaversive memory in insects Spotter et al. (2012) analyzed three samples of bees withdifferent levels of VSH and developed a differentiating panel of 44,000 SNPs. In next study they identified 6 SNPs associated with resistance towards the V. destructor. For four of them, candidate genes were proposed: AdoR,Cdk5alpha, Octbeta2R, and Obp1. The identified SNPs are notlocated in candidate genes themselves, but are localized nearthem. Therefore, their role in the formation of VSH phenotypehas yet to be proven. The authors substantiated the choice ofthese candidate genes by their function. Adenosine receptors(encoded by the AdoR gene) belong to the family of G proteincoupled receptors and are involved in extracellular adenosinesignaling. Adenosine is an important regulator of the nervoussystem; it is involved in the modulation of synaptic plasticity. Cdk5alpha encodes an activatorof the cyclin-dependent kinase gene Cdk5. Cdk5 regulatesmany cellular processes ,and it has been shown that in the Asian bee A. cerana Cdk5,together with its activator gene, is involved in the cell responseto oxidative stress . The biogenic amineoctopamine is an important neurotransmitter, modulator andhormone in invertebrates. It was shown that the octopaminereceptor gene Octbeta2R plays an important role in the formation of adaptations in the high-mountain population ofA. m. monticola . Obp1, expressed inthe antennae of worker bees, is responsible for the perceptionof queen pheromones , and probably forthe perception of other olfactory signalsIn addition to the colonies selected for hygiene, there arepopulations that coexisted with V. destructor for a long timewithout acaricide treatment . Thesepopulations have become the object of close scrutiny bygeneticists. Behrens et al. (2011) analyzed offspring of twohybrid queens from a Varroa tolerant colony from the Gotlandpopulation. They uncapped the sealed drone brood and estimated the number of mites with and without offspring. Colonies with mites without offspring were considered as resistant.Using 488 SSR markers for mapping, they identified a locuson chromosome 7 associated with this phenotype. This locuscontains two important candidate genes, orthologs of D. melanogaster genes, foxo and futsch . Lattorff et al. (2015) based ondata from Behrens et al. (2011) also analyzed bee coloniesfrom the Gotland population. They compared colonies before(2000) and after (2007) selection using 39 SSR markers onchromosomes 4 and 7. 11 candidate genes were identified onchromosome 7, including 10 protein-coding genes and onegene of long non-coding RNA, the target of which is unknown.The authors propose the oxidoreductase gene GMCOX18 asa promising candidate gene. Oxidoreductases are involved inglucose metabolism and cuticle biosynthesis. Therefore, theauthors hypothesized that the GMCOX18 may play a role inaltering substances secreted by bee larvae, which are requiredto trigger oogenesis in a mite.Among the genetic markers found in Varroa tolerant colonies using SNP mapping candidate genesinvolved in the synthesis of ecdysone are distinguished. It isknown that V. destructor cannot synthesize ecdysone itself and receives it from bees. Ecdysone is necessary for mite toactivate the reproductive cycle, while in insects it initiatesmolting and metamorphosis. Conlon et al. (2018) performedgenome-wide sequencing of drones from Varroa tolerantcolonies from Sweden and identified a locus on chromosome 15 associated with tolerance to the mite. This locusincludes three genes involved in ecdysone synthesis: Mblk-1,Cyp18a11 and Phantom. They continued their research byperforming genome-wide sequencing of drones from anotherVarroa tolerant population, the Toulouse population fromFrance . As a result, 9 SNPs associatedwith Varroa olerance were identified, and three of them werelocated in the transcription factor Mblk-1A search was also carried out for genes associated with thegrooming behavior of bees. Arechavaleta-Velasco et al. (2012)identified a locus on chromosome 5 and named it \u201cgroom-1\u201d.It includes 27 candidate genes, three of which are associated with the development of thenervous system and behavior.After the decoding of the honeybee\u2019s genome, studies of itstranscriptome were initiated. Differential gene expressionanalysis is often used to find candidate genes. It allows findingout how the activity of certain genes can affect the mechanismsof resistance.A comparative analysis of the transcriptome profile of colonies with high and low levels of hygiene behavior revealed 28 genes with increased expression in theformer. Most of them were located at previously identified loci.Of great interest as markers are genes of cytochrome P450gene superfamily ,which are over-expressed in non-hygienic bees. Cytochrome P450 enzymes degrade odorant and pheromone molecules, thereby reducing the ability of bees todetect infected brood.Transcriptomic analysis of colonies with VSH phenotypewas performed by two groups . Le Conte et al. (2011) identified 39 differentiallyexpressed transcripts in the brains of bees with VSH phenotype compared to control bees without VSH. Among thegenes with increased expression in the brain of VSH bees,the authors emphasize PRL-1, which encodes tyrosine phosphatase, and GB16747. It was later shown that the expressionof the GB16747, involved in the metabolism of ascorbate/aldarate, increases in response to infection with V. destructor. The Cyp4g11 and Obp3 genes andthree exons of the Dscam were under-expressed.Mondet et al. (2015) found 258 differentially expressedtranscripts in the antennae of worker bees with and withoutVSH phenotype. Among genes involved in redox metabolism 12 genes were over-expressed and 3 genes were underexpressed in bees with VSH. Four genes that control theimmune response, in particular the Def1 and Def2, wereunder-expressed. Of particular interest are genes associatedwith olfaction . Proteomic studies have also shown the involvementof the Obp genes (Obp17 and Obp18) in the formation ofVSH phenotype . Differential expression ofthe Obp genes indicates that the olfaction plays an importantrole in VSH.Analysis of two susceptible and two tolerant colonies showed that mite-tolerant bees undergochanges in the expression of genes that regulate the neuronsdevelopment and sensitivity, as well as the olfaction . Colonies were used as tolerantif they had not been treated with acaricides for 11 years andhad a low level of mite infestation (the authors counted mitesat the hive bottom 4 times a year for 5 years). In susceptiblecolonies the level of mite infestation was 10 times higher.Jiang et al. (2016), comparing transcriptome profiles of aV. destructor tolerant colony that survived without acaricidetreatment for 58 months and a susceptible colony that diedfrom varroatosis within 17 months, identified 6 candidategenes. Of these, 4 encode proteins of cytochrome P450. TheCyp6AS12 and Cyp6BE1 genes were over-expressed in pupaeof the tolerant mite-infested colony. Cyp6BE1 and Cyp9Q3were over-expressed in adults from a tolerant mite-free colonyrelative to the same mite-infested colony, whereas at the pupalstage there were no significant differences in expression levelsof the two genesConlon et al. (2019) measured the expression of Mblk-1,Cyp18a11, and Phantom genes in workers and drones larvaefrom Varroa tolerant colonies to verify the results of genomewide analysis. The expression pattern of genes involved inecdysone biosynthesis differed in drone larvae and worker larvae. If a mutation occurs in the genes responsible for the ecdysone synthesis,this can lead to a malfunction of the mite development cycle.It is possible that the preference of the drone brood by the miteand its more successful reproduction in it is a consequenceof the differences in the level of ecdysone expression in thedrone and bee brood.Transcriptome analysis confirmed the contribution ofthe neurexin I gene togrooming behavior. In colonies with a high level of groomingbehavior, the expression of this gene was increased .Transcriptomic studies were also performed for the Asianbee A. cerana. Ji et al. (2014) compared the transcriptomesof nurse bees of A. cerana before and after infection withV. destructor (after 24 hours). Among genes whose expressionincreased in response to mite infection were genes associated with olfaction , as wellas transcription factors (CREB-like 2-like and Mblk-1). Diaoet al. (2018) showed that A. cerana has more immune genesand genes encoding antimicrobial peptides than A. mellifera.However, A. cerana has fewer genes encoding odorant-bindingproteins (Obp) and olfactory receptors. This suggests thatafter the divergence, the European bee lost some of its genesdue to the lack of Varroa pressure, and when faced with it, A. mellifera activated other mechanisms. Differences in themethylation levels of genes responsible for learning andmemory were also recorded. The formation of long-termmemory and synaptic plasticity requires activation of neuronal signaling pathways. Transcriptome analysis showed that,in A. cerana, the expression of genes involved in signalingpathways increases inresponse to mite infection.The above mentioned studies narrowed down the list of potential loci and candidate genes that determine the resistanceof bees to the Varroa mite. Each of the studies identified itsown candidate genes. Overlaps (coincidences of results) wereobtained mainly for those studies in which the same methodsfor assessing the resistant phenotype were used (see the Table).In studies of the transcriptome profile of the brain and antennae ofVSH bees, a common candidate gene Cyp4g11 was identified. In the brain, Cyp4g11 expression was decreased, and inthe antennae it was increased. Decreased expression of theCyp4g11 gene in the brain was also shown for colonies withhigh hygiene behavior tested with FKB .In addition, the Cyp4g11 gene is located at one of the locipreviously identified in VSH bees . It iscurrently unknown what function Cyp4g11 performs in thehoney bee organism. Cytochrome P450 genes are involvedin ecdysteroids metabolism, detoxification of xenobiotics anddestruction of odorant molecules .A common candidate gene Obp3 was identified forVSH colonies (in two studies independently). In VSH bees,the expression of this gene is increased in antennas , while in the brain it is decreased . For one more gene from the Obp family, an overlapwas found: the Obp4, which are under-expressed in the brain of bees selected for FKB , is located atone of the loci on chromosome 9, identified earlier .The overlap was also shown for Varroa tolerant and VSH colonies. Dscamexpression (GB15141) was under-expressed in Varroa tolerantbees . In a study ,three exons of the Dscam gene also were under-expressed.Common candidate genes with the Asian bee A. cerana werealso identified. The resistance of the Asian bee to Varroa isthe key to understanding the resistance of the European bee.The presence of overlapping genes such as Mblk-1, Dscam,and Obp4 confirms this. Further research isneeded to establish role of these genes in the mechanism ofVarroa resistance in beesGenomic and transcriptome studies have shown that genesassociated with visual and olfactory perception, developmentand functioning of the nervous system (learning and memoryformation) play the main role in Varroa sensitive hygiene behavior. Receptor genes are of great interest, most of which belong to the family of G protein-coupled receptors . Some of the identifiedcandidate genes can be successfully used as markers for theselection of specific subspecies or lines of bees for which theywere obtained , someof genes needs testing on other populations . Some candidate genes areassociated with a general immune response . Further study of some genes , for example,genes for ecdysone biosynthesis, will help to shed light onthe nature of the parasite\u2013host relationship, in particular the question of why the mite in the original host reproduces moresuccessfully on the drone brood. Do not forget that the miteis a parasite, and, like many parasites, some of its life supportsystems are reduced. Finding these pain points of the Varroamite can also help fight varroatosis.The resistance of the honey bee to the V. destructor miteis under polygenic control. The European bee was able touse other gene pathways to provide its defense against theV. destructor, despite the short period of time since the miteinvasion. Establishing these pathways will help create amethodological basis for breeding Varroa resistant A. mellifera colonies.The authors declare no conflict of interest.Albo G.N., Cordoba S.B., Reynaldi F.J. 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G., Eto, M., Tarucha, S. & Kouwenhoven, L. P. Kondo effect in an integer-spin quantum dot. The original version of this Article contained an error in Ref. 10, which was incorrectly given with the wrong author list and article page range. The correct form of Ref. 10 is:Nature434, 484-488 (2005).Jarillo-Herrero, P., Kong, J., van der Zant, H. S. J., Dekker, C., Kouwenhoven, L. P. & De Franceschi, S. Orbital Kondo effect in carbon nanotubes. The original version of this Article contained an error in Ref. 21, which was incorrectly given with the wrong article title as \u201cKondo effect in a quantum dot at a high magnetic field\u201d. The correct form of Ref. 21 is:Phys. Rev. Lett. 88, 126803 (2002).van der Wiel, W. G., De Franceschi, S., Elzerman, J. M., Tarucha, S., Kouwenhoven, L. P., Motohisa, J., Nakajima, F. & Fukui, T. Two-stage Kondo effect in a quantum dot at a high magnetic field. All of these errors in references have been corrected in the PDF and HTML version of the Article."} +{"text": "We have read with interest the article by Monachesi et al. , in whicConsiderable rates of GIP positivity similar to these claimed as \u201cfalse positives\u201d here have been previously reported in celiac patients on a GFD ,4. OtherIn study B, it is normal to find negative GIP tests in urine when the volunteers ingested 5 or 10 mg of gluten. However, it was not clear why they used the urine tests to detect levels of GIP below the manufacturer specifications which are indicated for detection of 50\u2013500 mg gluten consumption.In conclusion, the suggestions of Monachesi et al. of falseGuarantor of the article: Carolina Sousa, PhD.Specific author contributions: C.S., I.C., \u00c1.C., L.C., V.S., A.R.-C. and M.L.M.: data collection and interpretation; manuscript preparation and review.Financial support: None to report.Potential competing interests: A.C. is the founder and current CEO of Biomedal S.L. L.C. is an employee and PhD student at Biomedal S.L. The method of this letter was included in a patent application (No. P201400569) by C.S., A.C., and M.L.M. as inventors. Other authors have declared no conflict of interest."} +{"text": "Nemesis Furfaro & Mariottini, 2021, was recently introduced for an independent lineage of aeolid nudibranchs, and Dondice banyulensis Portmann & Sandmeier, 1960, established as its type species. Anyway, the presence of a senior homonym, Nemesis Risso, 1826, was evidently missed. In fact, in 1826, Risso established this genus for a group of Copepoda and according to the Principle of Priority (ICZN) only the senior homonym may be used as a valid name. Therefore, a new replacement name is here proposed. Furthermore, the genus name Nanuca Er. Marcus, 1957, has priority over Dondice Er. Marcus, 1958 and consequently, the species in this clade should be classified under Nanuca, mostly as new combinations.The genus Nemesis Furfaro & Mariottini, 2021, was introduced based on evidence from a recent integrative systematic study [Dondice banyulensis Portmann & Sandmeier, 1960 [Nemesis Risso, 1826 [Nanuca Er. Marcus, 1957 [Dondice Er. Marcus, 1958 [Nanuca, mostly as new combinations.The genus so, 1826 Genus urn:lsid:zoobank.org:pub:DEED49D6-F89B-4D68-A8A3-E1071197264CType species.Dondice banyulensis Portmann & Sandmeier, 1960.Etymology. The genus name Nemesignis comes from the union of the Greek word Nemesis, that recalls the homonymous Greek goddess and her role of compensatory justice, with the Latin word Ignis, that is the fire that burns and blazes, linked to the fiery red colour of the type species of the genus.Included species.N. banyulensis .Nanuca Er. Marcus, 1957Genus Type species.Nanuca sebastiani Er. Marcus, 1957Dondice Er. Marcus, 1958 comb. nov. [N. occidentalis comb. nov., N. parguerensis comb. nov. [N. trainitoi comb. nov. [mb. nov. , N. traimb. nov. .Nemesis Furfaro & Mariottini, 2021, made this latter genus name as invalid and invoked the need for a replacement name according to the rules of the ICZN. Therefore, Nemesignisnom. nov. is here proposed as the new replacement name, under the Article 60.3 of ICZN and consequently, Nemesignis banyulensis is its type species. Finally, since Nanuca Er. Marcus, 1957 has priority over Dondice Er. Marcus, 1958, the species in this clade should be classified under Nanuca, as Nanuca galaxiana comb. nov., N. occidentalis comb. nov., N. parguerensis comb. nov., N. trainitoi comb. nov.The presence of a senior homonym, which has priority over the recently stated"} +{"text": "This reference has been replaced with the original article as follows:J. Autoimmun. 7:67\u201391. https://doi.org/10.1006/jaut.1994.1006.Seelig, H.P., P. Schranz, H. Schr\u00f6ter, C. Wiemann, and M. Renz. 1994. Macrogolgin\u2014a new 376 kD Golgi complex outer membrane protein as target of antibodies in patients with rheumatic diseases and HIV infections. This change does not affect the study or its conclusions. The error appears only in print and in PDF versions downloaded on or before June 7, 2021."} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-020-75956-z, published online 05 November 2020Correction to: William A. Myers, Pragney Deme and Norman J. Haughey were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article.The Author Contributions section now reads:H.M.W. and T.L.C. designed the study. H.M.W. and J.W.M. acquired funding. T.L.C. and S.J.E. conducted the experiments. T.L.C., W.A.M., and P.D. conducted sample analysis and analyzed the data, T.L.C. and H.M.W. interpreted the results, and drafted the manuscript. All authors reviewed the manuscript and approved the final version to be published.The Acknowledgements section now reads:This research was supported by funding provided through the Real Science Initiative Grant by Balchem Corporation , The New York State Centers for Advanced Technology, and National Institute of Food and Agriculture, U.S. Department of Agriculture, Award Number 2016-67015-24573. Gratitude is extended to Sandra J. Bertics (University of Wisconsin-Madison) for her technical assistance."} +{"text": "Elymus breviaristatus and Elymus sinosubmuticus are perennial herbs, not only morphologically similar but also sympatric distribution. The genome composition of E. sinosubmuticus has not been reported, and the relationship between E. sinosubmuticus and E. breviaristatus is still controversial. We performed artificial hybridization, genomic in situ hybridization, and phylogenetic analyses to clarify whether the two taxa were the same species.E. breviaristatus (StYH)\u2009\u00d7\u2009E. sinosubmuticus was observed. It illustrated that E. sinosubmuticus was closely related to E. breviaristatus. Based on genomic in situ hybridization results, we confirmed that E. sinosubmuticus was an allohexaploid, and the genomic constitution was StYH. Phylogenetic analysis results also supported that this species contained St, Y, and H genomes. In their F1 hybrids, pollen activity was 53.90%, and the seed setting rate was 22.46%. Those indicated that the relationship between E. sinosubmuticus and E. breviaristatus is intersubspecific rather than interspecific, and it is reasonable to treated E. sinosubmuticus as the subspecies of E. breviaristatus.The high frequency bivalent at metaphase I of pollen mother cells of the artificial hybrids of E. sinosubmuticus and E. breviaristatus were StYH, and they are species in the genus Campeiostachys. Because E. breviaristatus was treated as Campeistachys breviaristata, Elymus sinosubmuticus should be renamed Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang subsp. sinosubmuticus (S. L. Chen) Y. H. Zhou, H. Q. Zhang et L. Tan.In all, the genomic constitutions of The online version contains supplementary material available at 10.1186/s12870-022-03441-y. Elymus sensu lato (Elymus s.l.) is the largest genus of Triticeae, and it contains seven basic genomes: St, H, P, W, Ns, Y, and Xm [St genome is from Pseudoroegneria (Nevski) L\u00f6ve, H genome is from Hordeum L., P genome is from Agropyron Gartn., W genome is from Australopyrum (Tzvelev) L\u00f6ve, Ns genome is from Leymus Hochst. The origin of Y and Xm is still unknown [Elymus s.l. was further divided into ten genera, including Elymus sensu stricto (Elymus s.s.) (StH), Roegneria C.Koch (StY), Hystrix Moench (StH/NsXm), Stenostachys Turcz. (HW), Douglasdeweya C.Yen, J.L.Yang et B.R.Baum (StP), Kengyilia C.Yen et J.L.Yang (StYP), Campeiostachys Drobov (StYH), Anthosachne Steudel (StYW), Pascopyrum \u00c1. L\u00f6ve (StHNsXm), and Connorochloa Barkworth, S.W.L.Jacobs et H.Q.Zhang (StYWH) [St and H genomes, it is challenging to distinguish Campeiostachys from Elymus s.s. based on single or combined morphological characters [Elymus s.s. and Campeiostachys is still unknown, resulting in the classification of many species in these two genera remains controversial [The tribe Triticeae includes about 450 species, of which about 75% are polyploid , 2. Sinc, and Xm , 10\u201312. unknown , 13. Bas (StYWH) , 13\u201316. aracters , 17. Moroversial . AlthougElymus breviaristatus (Keng) Keng ex Keng f. and Elymus sinosubmuticus S. L. Chen is sympatric species mainly distributed on hillsides in Sichuan, Qinghai, and Ningxia, China [E. breviaristatus has short awn (2\u20135\u00a0mm), while E. sinosubmuticus possesses degenerated awn only 0-2\u00a0mm in length [E. breviaristatus and E. sinosubmuticus were the same species by comparing the leaf anatomical characteristics.a, China , 18\u201321. n length , 19, 22.n length . Zhang en length suggeste1 at meiosis metaphase can be used to indicate chromosome homology and evolutionary relationship between genus or species in Triticeae [E. breviaristatus and E. sinosubmuticus are allohexaploid (2n\u2009=\u20096x\u2009=\u200942) perennial wheatgrass [E. breviaristatus is tetraploid with StH genome. Based on the genome analysis and GISH, Yang et al. [E. breviaristatus was a hexaploid with the StYH genome and treated it as Campeistachys breviaristata (Keng) Y.H.Zhou, H.Q.Zhang et C.R.Yang. However, the genome composition of E. sinosubmuticus has not been reported at present.The chromosome pairing behavior of hybrid Friticeae , 26. Genriticeae \u201332. Cytoeatgrass , 21, 33,eatgrass reportedg et al. recognizAcc1 and DMC1 sequences have higher evolutionary rates and have been widely applied in the phylogenetic study of the genera of Triticeae, such as Triticum, Kengyilia, Leymus, Roegneria, Hystrix, etc. [E. sinosubmuticus and explore the biosystematics relationships between E. breviaristatus and E. sinosubmuticus.Cytological and phylogenetic analyses are practical tools to determine the genome composition and explore the interspecies and intergeneric relationships of the species in Triticeae \u201339. Moleix, etc. \u201349. In tE. breviaristatus\u2009\u00d7\u2009E. sinosubmuticus. We observed the chromosome pairing of PMCs at metaphase I (MI) of parents and hybrids , showing an average of 0.50 univalents, 20.62 bivalents, 0.06 trivalent, and 0.02 quadrivalents (Table StYH genome constitution.Five hybrids were obtained from the combination of ds Table . MeiosisE. breviaristatus and E. sinosubmuticus) showed a high level of stainability, was 92.91% and 92.32%, respectively. The percentage of stained pollen grains of the hybrids was comparatively high at 53.90%. The seed setting rate of E. breviaristatus and E. sinosubmuticus were 89% and 87%, respectively. And the seed setting rate of their hybrids was 22.46%, indicating that the two species were highly affinities.Pollen grains of parents Nevski) when blocked by the H genome (from Hordeum bogdanii Wilensky) , and 14 chromosomes were labeled by the H probe (in green) Fig.\u00a0a. And 14Acc1) sequences length of E. sinosubmuticus ranged from 1421 to 1443\u00a0bp, and E. breviaristatus went from 1428 to 1441\u00a0bp. The Acc1 data matrix of sequences was analyzed based on maximum likelihood (ML) using the model TIM1\u2009+\u2009I\u2009+\u2009G (-Ln likelihood\u2009=\u20098147.4309). The assumed nucleotide frequencies were A\u2009=\u20090.2555, C\u2009=\u20090.1794, G\u2009=\u20090.2116, T\u2009=\u20090.3535. The tree generated by Bayesian analysis was similar to ML analysis. All the Acc1 sequences were grouped into six clades . Clade III included in the Dasypyrum, Roegneria, and Campeiostachys species . Clade IV grouped with the Hordeum, Elymus, and Campeiostachys species .The Acetyl-CoA carboxylase (DMC1) sequences were used for ML analysis, Bromus sterilis as the outgroup. TPM2uf\u2009+\u2009G as the best-fit model, -Ln likelihood\u2009=\u20095355.5355. The assumed nucleotide frequencies were A\u2009=\u20090.2576, C\u2009=\u20090.2120, G\u2009=\u20090.2085, T\u2009=\u20090.3220. The tree generated by Bayesian analysis was similar to ML analysis. The DMC1 sequences from E. breviaristatus and E. sinosubmuticus were divided into three clades , and tetraploid species (Elymus and Roegneria), and hexaploid species (Campeiostachys) . In clade II, their sequences grouped with the species of the genus Roegneria and Campeiostachys . In clade III, grouped with the diploid species (Hordeum) and the species of the genus Elymus and Campeiostachys . Clade IV and clade V grouped with the other diploid species in Triticeae Nevski and R. heterophylla (Bornm. ex Melderis) C. Yen, J. L. Yang and B. R. Baum) and cryptic genera (such as Elymus and Campeiostachys) in Triticeae [E. sinosubmuticus into the genus Campeiostachys based on the genome analysis, GISH, and phylogenetic analyses results.In this study, genome analysis, GISH, and phylogenetic analyses indicate that ostachys . Previouribution , 9, 21. riticeae , 8, 50. E. breviaristatus and E. sinosubmuticus are the same species [E. breviaristatus and E. sinosubmuticus had little difference in leaf anatomy, and it was difficult to distinguish. Therefore, E. breviaristatus and E. sinosubmuticus were the same species, and E. sinosubmuticus should be a synonym for E. breviaristatus [E. breviaristatus and E. sinosubmuticus we observed were differing little. Both species are perennial tufted plants, culms erect. Leaf-sheaths glabrous, leaf-blades flat, margins ciliate. Spikes nodding or curved, with sparse remote spikelets, two spikelets on each rachis node, green or purple-tinged. Lemma is lanceolate and with five nerves. Palea is equal to lemma. Anthers yellow. The most significant difference is the length of the lemma awn, E. sinosubmuticus is only 0-2\u00a0mm, and E. breviaristatus is 2-6\u00a0mm. In addition, many types of interspecific variations were found in our field studies.There is still debate whether or not species , 23. Kar species . From thristatus . Convers1 can indicate that the parents are closely related [1 of E. breviaristatus and E. sinosubmuticus has a high-frequency bivalent at MI , suggesting that the three genomes of E. breviaristatus and E. sinosubmuticus has high homology, and they are closely related. But the percentage of stained pollen grains of hybrids was 53.90%, and the seed setting rate was 22.46%. This suggests genetic differentiation between the two taxa, leading to a degree of reproductive isolation. Yang et al. [E. breviaristatus was a hexaploid with the StYH genome and treated it as Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang. Combined with morphological characteristics and the fertility of hybrids, E. sinosubmuticus should be classified into the genus Campeiostachys as the subspecies of E. breviaristatus and renominated as Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang subsp. sinosubmuticus (S. L. Chen) Y. H. Zhou, H. Q. Zhang et L. Tan.A high chromosome pairing frequency of hybrid F related , 52. A s related . Accordig et al. reportedElymus sinosubmuticus is allohexaploid wheatgrass, and the genome composition is StYH. Its morphological characteristics are very similar to E. breviaristatus. Simultaneously, E. sinosubmuticus and E. breviaristatus have a degree of reproductive isolation, and it is reasonable to treat E. sinosubmuticus as the subspecies of E. breviaristatus. Because E. breviaristatus was treated as Campeiostachys breviaristata by Yang et al. [, E. sinosubmuticus should be renamed as Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang subsp. sinosubmuticus (S. L. Chen) Y. H. Zhou, H. Q. Zhang et L. Tan.g et al. , therefoElymus breviaristatus and Elymus sinosubmuticus were collected from the field in Sichuan Province, China, and numbered ZY 17,004 and ZY 17,008 respectively. No permissions were necessary to collect seed samples. Yonghong Zhou and Haiqin Zhang identified the two plant materials. They were used for artificial hybridization, and the materials and F1 hybrids were cultivated in the greenhouse at Hongyuan, Sichuan. The voucher specimens of E. breviaristatus and E. sinosubmuticus were deposited in the Herbarium of Triticeae Research Institute of Sichuan Agricultural University, China (SAUTI). Apart from E. breviaristatus and E. sinosubmuticus, diploid species and relative polyploid species with different genome combinations in Triticeae were also applied for phylogenetic analyses. The basic information about these sequences is listed in Additional file In our study, E. breviaristatus was used as the male parent when crossed with E. sinosubmuticus, and E. sinosubmuticus was used as the male when hybridized with E. breviaristatus. The chromosome pairing of pollen grains of hybrids and parents was examined after fixing by Carnoy's Fluid II for 24\u00a0h. The mean pairing frequency of hybrids and parents at MI is described by Kimber and Alonso [2-IK solution.The hybridization procedure is as follows: after 2\u20133\u00a0days of the emasculation of the female parent, repeat pollinations with the corresponding mature pollens of the male parent were carried out. The female parents were used a plastic bag to isolate the pollen throughout the whole process. In crossing combination, d Alonso . Mature The roots were collected from adult plants, treated with nitrous oxide for three hours, fixed with 90% glacial acetic acid for 5\u00a0min, and kept with 70% alcohol. The chromosome was prepared by drop methods . Using tAcc1 and DMC1 sequences were amplified with primers listed in Table The Additional file 1. Additional file 2."} +{"text": "Violahuizhouensis (Violaceae), a new species from Xiangtoushan National Nature Reserve of Guangdong Province in China, is described and illustrated. The new species is most similar to V.guangzhouensis, but it can be easily distinguished by its much stouter rhizome, lack of aerial stem, dense pubescence of the basal pedicel and the whole plant. Our phylogenetic analysis, based on ITS sequences, confirms that the new species belongs to V.sect.Diffusae. Violahuizhouensis, was collected on Mount Xiangtoushan.Mount Xiangtoushan in Guangdong Province, China, is located in a subtropical zone with abundant rainfall, mainly a low-lying hilly landform, but has an extremely high altitude compared with the surrounding environment. A large area of granite in this region is exposed on the surface due to intense erosion and denudation and there are climax lithophytic vegetation communities with a high level of biodiversity. During fieldwork in March 2018 for the investigation of the biodiversity patterns in this mountainous region, a distinct new species, Viola L. is the largest genus of family Violaceae, with approximately 525\u2013600 species around the world .Leaf material of the putative new species and its related species ML). ML was run by Iqtree 2.0.3 (Minh 2020), selecting best-fit model TIM+F+G4 with 2000 bootstraps. Phylogenetic analyses, based on Bayesian Inference (BI) were carried out using MrBayes version 3.1.2 (Huelsenbeck and Ronquist 2001). Bayesian analysis was run with four chains for 200,000 generations with the first 25% of sampled trees discarded as burn-in. Main quantitative characteristics of the putative new species and V.guangzhouensis were statistically analysed using IBM SPSS version 22.0.Total DNA was extracted with the modified CTAB method . The regML and BI analyses produced similar topology and V.guangzhouensis A.Q. Dong, J.S. Zhou & F.W. Xing, clustered into their own species clade respectively, with strong support (BS = 100% for V.huizhouensis and BS = 98% for V.guangzhouensis). The V.huizhouensis clade clustered with the V.guangzhouensis clade, forming a sister relationship (BS = 100%). Then, the two species, together with V.yunnanensis W. Beck. & H. De Boiss., V.diffusa Ging., V.nanlingensis J.S. Zhou & F.W. Xing and V.lucens W. Beck., constituted a monophyletic clade (BS = 99%). Quantitative characteristics and a statistical analysis showed that there was a significant difference between V.huizhouensis and V.guangzhouensis in the diameter of rhizome and the leaf shape . of two anterior stamens 0.7\u20131 mm long. Ovary ovoid to ellipsoid, ca. 0.7 mm diam., puberulent; style ca. 1.0 mm long, conspicuous geniculate at base; stigma thickly margined on lateral sides, slightly raised at central part, shortly beaked at the apex. Capsule with brownish lines at maturity, ovoid, 6\u20138 mm long. Seeds brown, ovoid, 1\u20131.5 mm long.Flowering from March to June, fruiting from April to July.Violahuizhouensis were only discovered in Darenyan, Xiangtoushan National Nature Reserve, Guangdong Province. The species was observed to grow on damp cliffs and rocks in broad-leaved forests at altitudes between 400 and 800 m. Its known localities are well protected and more field investigations are needed to determine its distribution.Populations of Violahuizhouensis should be a member of section Diffusae (W. Beck.) C.J. Wang, which was formerly treated as subsection Diffusae under section Viola by V.huizhouensis on morphological grounds could be V.guangzhouensis. They shared several characteristics, for example, the well-developed rhizome and the bearded lateral petals. The new species can be distinguished from V.guangzhouensis, however, by its much stouter rhizome; lack of aerial stem; different leaf shape ; and dense pubescence of the basal pedicel and the whole plant , then they form a well-supported clade with V.yunnanensis, V.diffusa, V.nanlingensis and V.lucens (BS = 99%) C.J. Wang (In conclusion, the morphological differences and the molecular phylogenetic results provide sufficient evidence for treating .J. Wang ."} +{"text": "Adv. Sci. 2021, 8, 210271810.1002/advs.202102718DOI: In the originally published version of the article, one grant number is incorrect in the Acknowledgements. Please find the correct Acknowledgements here:"} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-020-68516-y, published online 17 July 2020Correction to: The Author Contributions section in this Article was incomplete.\u201cS.M. performed tissue culture and flow cytometric studies, participated in design of experiments and interpreted the data; A.M. conceptualization and design of experiments, data analysis and interpretation, major part in manuscript writing; A.M. performed tissue culture and flow cytometric studies, performed data analysis; N.R.M. performed tissue culture and flow cytometric studies; L.I.P. performed design and synthesis of chemical compounds, writing and critical reading of manuscript; J.R. performed design and synthesis of chemical compounds, conceptualization of experiments, writing and critical reading of manuscript and data interpretation; V.\u010c.\u010c. conceptualization and design of experiments, data analysis and interpretation and writing of manuscript. All authors read and approved the final manuscript.\u201dnow reads:\u201cS.M. performed tissue culture and flow cytometric studies, participated in design of experiments, interpretation of the data, writing and critical reading of the manuscript; A.M. conceptualization and design of experiments, data analysis and interpretation, major part in manuscript writing; A.M. performed tissue culture and flow cytometric studies, performed data analysis; N.R.M. performed tissue culture and flow cytometric studies; L.I.P. performed design and synthesis of chemical compounds, writing and critical reading of manuscript; J.R. performed design and synthesis of chemical compounds, conceptualization of experiments, writing and critical reading of manuscript and data interpretation; V.\u010c.\u010c. conceptualization and design of experiments, data analysis and interpretation and writing of manuscript. All authors read and approved the final manuscript.\u201dThe original Article has been corrected."} +{"text": "Whole genome and whole exome sequencing technologies play a very important role in the studies of the genetic aspects of the pathogenesis of various diseases. The ample use of genome-wide and exome-wide association studymethodology (GWAS and EWAS) made it possible to identify a large number of genetic variants associated with diseases.This information is accumulated in the databases like GWAS central, GWAS catalog, OMIM, ClinVar, etc. Most of the variants identified by the GWAS technique are located in the noncoding regions of the human genome. According to theENCODE project, the fraction of regions in the human genome potentially involved in transcriptional control is many timesgreater than the fraction of coding regions. Thus, genetic variation in noncoding regions of the genome can increase thesusceptibility to diseases by disrupting various regulatory elements . However, identification of the mechanisms of influence of pathogenic genetic variants on the diseases risk is difficultdue to a wide variety of regulatory elements. The present review focuses on the molecular genetic mechanisms by whichpathogenic genetic variants affect gene expression. At the same time, attention is concentrated on the transcriptional levelof regulation as an initial step in the expression of any gene. A triggering event mediating the effect of a pathogenic geneticvariant on the level of gene expression can be, for example, a change in the functional activity of transcription factor binding sites (TFBSs) or DNA methylation change, which, in turn, affects the functional activity of promoters or enhancers. Dissecting the regulatory roles of polymorphic loci have been impossible without close integration of modern experimentalapproaches with computer analysis of a growing wealth of genetic and biological data obtained using omics technologies.The review provides a brief description of a number of the most well-known public genomic information resources containing data obtained using omics technologies, including (1) resources that accumulate data on the chromatin states and theregions of transcription factor binding derived from ChIP-seq experiments; (2) resources containing data on genomic loci,for which allele-specific transcription factor binding was revealed based on ChIP-seq technology; (3) resources containingin silico predicted data on the potential impact of genetic variants on the transcription factor binding sites Experimental datasets of comparable volumehave been accumulated in a number of other databases ongenotype-phenotype associations .At present, largely due to the widespread use of the technologyof genome-wide and exome-wide association study (GWASand EWAS), a large number of polymorphisms associatedwith diseases have been identified. For example, GWAScentral ,but the molecular mechanisms underlying these associationsare extremely poorly understood. This is due to the fact thatonly a relatively small proportion of pathogenic GVs is locatedin the coding regions of the human genome, changes in thenucleotide sequence of which disrupt the structure and function of proteins. A huge mass of polymorphic loci associatedwith diseases is located in non-coding regions of the genome. For example, according to GWAS data, ~90 % of thetotal number of variants associated with diseases are locatedin noncoding regions of the human genome .It is known that non-coding regions of the genome containregions that perform a wide range of regulatory functions:promoter regions, enhancers, negative regulatory elements,nuclear matrix attachment regions, regions that determinethe structure of topologically associating domains (TADs),and other features of 3D organization of genome .The proportion of regions in the human genome potentiallyinvolved in the transcriptional regulation is extremely high.According to the ENCODE project, the chromatin regionscorresponding to the peaks of transcription factor(TF) bindingidentified by the ChIP-seq occupy ~8.1 % of the total genomicDNA , which is significantly higher than the proportion of coding regions of thehuman genome (~1.2 %). Considering that not all known TFsand not all cell lines were studied in the ENCODE project,an obviously larger fraction of genomic DNA is involved inthe interaction with TFs. The total length of human genomeregions with enhancer-associated chromatin features alsosignificantly exceeds the total size of the coding regions: forexample, in only one cell type studied (H1-ES), enhancerregions occupy ~3.2 % .Studies aimed at identifying the mechanisms of the influence of pathogenic GVs on the predisposition to diseases arecarried out very actively, which is reflected in a number ofreview publications .The most discussed effect of pathogenic GVs is a change inthe binding activity of TFBSs . It has also been shown that polymorphic loci can be associated with alteration of DNA methylationpatterns and modifications of histoneproteins , with structural change in chromatinloops and, as one ofthe manifestations of this process, with changes in the TADsstructure . Examples ofsuch effects will be discussed below (Table 1).The effects of genetic variants on the functionalactivity of transcription factor binding sitesThe key role in the transcriptional regulation is played bytranscription factors \u2013 proteins that can specifically bind toDNA of the regulatory regions of genes and to initiate the transcription complexes formation. The human genome containsmore than 1500 genes encoding TFs .TF binding sites, as a rule, have a length of 10\u201325 nucleotides.Nucleotide substitutions, as well as short insertions/deletions at polymorphic loci, can disrupt TFBSs or create themde novo (see Table 1), and this, in turn, can have both negativeand positive effects on the level of gene transcription . Such GVs (and the corresponding polymorphic loci) that affect the transcriptionalactivity of genes are usually called regulatory variants .Pathological can be bothan allelic variant of the DNA sequence containing a disruptedTFBS and an allelic variant, leading to creation of TFBS de novo (see Table 1).Pathological GVs, affecting the binding activity of TFBSs,can be located not only in promoter regions, but also in regulatory regions located at considerable distance from transcription start sites (TSSs) of genes: enhancers , regulatoryregions with repressive function , and TAD boundary regions (see Table 1).For example, the rs1421085 T\u2192C substitution associatedwith obesity impairs the functioning of the negative regulatory region controlling expression of the IRX3 and IRX5 genes. The rs1421085 locus is located inthe intron of the FTO gene at a considerable distancefrom the transcription start sites of IRX3 and IRX5 . Normally, the DNA region containingallele T interacts with a repressor factor ARID5B, leadingto a decrease in transcriptional activity of IRX3 and IRX5genes. In carriers of the mutant variant of the DNA sequence, the binding site of the ARID5B repressor factor isdisrupted, which causes an excessively high expression of theIRX3 and IRX5 genes and activates adipogenesis .Occasionally a nucleotide substitution at a polymorphiclocus disrupts the TFBS and this, in turn, affects the functionalactivity of the TAD (see Table 1). This effect was found inthe case of A\u2192G (rs2001389), associated with the risk ofpancreatic cancer . The rs2001389 locus is located inthe region that determines the structure of chromatin loopswithin the TAD. This TAD contains 91 genes and is formedby spatially adjacent chromatin regions . TheDNA region containing the risk allele G is characterized by areduced ability to interact with CTCF, which in this case actsas a structural protein of chromatin. Normally, CTCF bindingensures the functioning of one of the regions that determinesthe structure of chromatin loops within the considered TAD.The pathogenic allele G alters the activity of CTCF bindingmotif within TAD boundary disrupting the stability of corresponding 3D structure of chromatin. As a result, the expression of the genes within this TAD is impaired. In this case,the greatest decrease in MFSD13A expression is observed.The effects of genetic variability on DNAmethylation and gene transcriptional activityDNA methylation doesn\u2019t change the nucleotide sequenceand is the addition of a methyl group to the fifth carbon atomof cytosine . An increase inthe level of DNA methylation, as a rule, leads to a long-terminactivation of the expression of genes lying in the methylatedregion, since, according to the generally accepted concept,methylation of a DNA region facilitates recruiting proteincomplexes, containing histone deacetylase (HDAC) . DNA methylation can alsodecrease the ability of some TFs to interact with DNA: it isknown that CTCF factors and factors from the ETS familyhave such sensitivity to methylation . Incontrast, another transcription factor, ZFP57, binds only tomethylated DNA . Thus, cytosinemethylation can activate different mechanisms of gene transcription regulation, and not always an increase in the methylation level of the regulatory DNA region is associated witha decrease in the expression of the corresponding gene .Genetic variability affects significantly the methylation ofDNA regions that have regulatory potential. Thus, a genomewide analysis of the methylation patterns of DNA collectedfrom 24 subjects from Norfolk Island genetic isolate , identified 12,761 regions containing at least twoCpG dinucleotides and having an allele-specific methylationlevel. In most cases (98 %), regions with allele-specific methylation level are co-localized with single nucleotide variantspresented in dbSNP .This study also analyzed the locationof allele-specific methylation regions relative to the set ofpolymorphic loci associated with human diseases extractedfrom the GWAS catalog database. It turned out that polymorphic loci associated with diseases overlap with regions ofallele-specific methylation twice more often than it would beexpected by chance. This means that the change in methylation levels due to genetic variability is one of the factors thatincrease the risk of disease.As an example, consider the rs174537 (G\u2192T) polymorphic locus located in the enhancer of the FADS1 and FADS2genes encoding fatty acid desaturases 1 and 2. The T variantof the rs174537 locus is associated with an increased risk ofpathological disturbances of lipid metabolism (see Table 1).It was shown that individuals that have rs174537(T) allelehad a higher methylation level of the regulatory region of theFADS1 and FADS2 genes in human liver ,which led to the suppression of the transcriptional activity ofFADS1 and FADS2Occasionally, in one of the allelic variants, DNA demethylation occurs, initiated by TF binding to DNA (see Table 1).For example, such a mechanism was revealed for rs612529T\u2192C. This locus is located in the promoter region of theVSTM1 . The low expression of VSTM1 in monocytesprovokes the development of atopic dermatitis. In this celltype, the promoter region containing the protective variant Tinteracts with the transcription factor PU.1 more actively than the other one containing variant C. PU.1 initiates DNAdemethylation by recruiting DNA demethylases . As a result, carriers of the T allele have completelydemethylated VSTM1 promoter, and VSTM1 expression isactivated. In carriers of pathogenic variant C, the interactionof PU.1 with DNA is disrupted, as a result, methylation levelof the VSTM1 promoter is elevated, and this is accompaniedby a decrease in VSTM1 expression .The effects of the genetic variabilityon the chromatin states and chromatinspatial organizationPathogenic GVs may impaire the chromatin state . There are cases when the presence of a pathogenic GV was accompanied by a change in the patterns ofhistone modification and the appearance (or disappearance)of DNase I hypersensitive sites . In thesecases, allele-specific contacts between promoters and enhancers were identified, the number of which correlated with theactivity of the enhancer regions.There are also known cases when structural variations ofthe genome lead to a changein the spatial organization of chromatin, thereby disrupting the expression of genes associated with pathologicalprocesses . Forexample, the expansion of CGG trinucleotide repeats in the5\u2032-untranslated region (5\u2032-UTR) of the FMR1 gene, associatedwith the fragile X syndrome, disrupts the structure of TAD,that includes FMR1 . Normally, FMR1 isvery close to the 5\u2032-boundary region of TAD . The DNA region corresponding to this 5\u2032-boundaryis hypomethylated and is occupied by CTCF. In individualswith mutation-length CGG triplet repeats (more than 100),this boundary is ablated (this region is hypermethylated andits CTCF occupancy is lost). As a result, TAD1 dissolves andthe boundary of the other TAD shifts to the 3\u2032-region of FMR1. Therefore, FMR1 iswithin the TAD2, which normally does not contain this gene.In this case, FMR1 promoter is hypermethylated, and FMR1expression is inactivated .To study molecular-genetic mechanisms of the effect of genome variability on the 3D chromatin structure, it is necessaryto reconstruct the spatial genome organization. The followingbasic levels of the 3D genome organization have been identified: (1) regulatory DNA loops that bring together promotersand enhancers; (2) topologically associating domains(TADs),within which DNA regions have more contacts with eachother than with neighboring domains; (3) A and B compartments corresponding to transcriptionally active and condensedchromatin; and finally (4) chromosome territories . Disruption of 3D contactsbetween promoters and enhancers within the TAD, caused, forexample, by chromosomal rearrangements, can significantlyaffect the transcriptional activity of a gene, increasing risk ofdiseases .The Institute of Cytology and Genetics SB RAS has developed an experimental computer approach for prediction physical contacts between promoters and enhancers withinthe 3D chromatin structure . The approach is based on the following information: (1) cell type;(2) cell-specific localization of enhancers in the linear genome(from the ENCODE database); (3) transcriptional activity ofpromoters (from RNA-seq experiments); (4) boundaries ofchromatin loop extrusion (based on ChIP-seq mapping ofCTCF occupancy in a definite cell type); (5) orientation ofCTCF binding motifs (based on motif prediction pipeline);(6)Aor B chromatin compartment (according to Hi-C experiments). Analysis of these data using the original 3DPredictorprogram , developed on the basisof machine learning algorithms, allows to predict the frequencies of physical contacts between promoters and enhancers inthe 3D genome structure with an accuracy that exceeds theaccuracy of other known prediction methods.The 3DPredictor was used to analyze the 3D genome structure in homozygous DelB/DelB mice that have a deletion ofthe 1.5 Mb genomic region containing Epha4. This deletionis accompanied by the appearance of additional contacts between Pax3 gene and Epha4 enhancer region, altering Pax3expression and leading to brachydactyly. Mice with the DelB/DelB genotype are a genetic model of human pathology accompanied by limb malformations .Testing 3DPredictor on this model has demonstrated the highefficiency of the program: in homozygous DelB/DelB mice,ectopic contacts between the Pax3 gene and Epha4 enhancers cluster were predicted , andthese predictions were in good agreement with the experimental data. Genetic variability: combined analysisof heterogeneous big biological and genetic dataAs noted above, many polymorphic loci associated with diseases are located at a considerable distance from the codingregions of genes . Additional studies are needed to identify themolecular-genetic mechanisms of the influence of such GVson the predisposition to diseases. The purpose of such studiesis to clarify the regulatory role of GVs. A typical example isthe work , which made it possible to finda functionally active regulatory variant rs4321755 associatedwith the risk of breast cancer. The rs4321755 locus is locatedin a distant enhancer that regulates the expression of theMRPS30 and RP11-53O19.1 genes (see Table 1). It turned outthat in the presence of the pathogenic variant rs4321755(T),a new GATA3 binding site is created. The transcription factorGATA3 increases the functional activity of the enhancer, thisleads to the formation of more contacts between the enhancerand the divergent promoter of the MRPS30 and RP11-53O19.1genes, and increased expression level of these genes. To identify this functionally significant regulatory variant, the authorsdeveloped an integrated experimental computer method basedon a combined analysis of heterogeneous big biological andgenetic data, including: (1) data on allele-specific expression obtained from RNA-seq in combination with data onhaplotypes; (2) expression quantitative trait loci (eQTL);(3) genomic distribution of DNAse I hypersensitive sites;(4) localization of ChIP-seq peaks from ENCODE and GEOdatabases; (5) localization of regulatory motives predicted bycomputer programs. Similar scenarios for integrated experimental computer research have been implemented in the otherstudies .This kind of research became possible due to (1) the development of modern high-throughput experimental approachesthat allow producing data of different types on a genome-widescale ; (2) development of public informationresources accumulating such experimental data. Table 2 provides a brief description of information resources containinggenomic data obtained on the basis of omics technologies andused to study the mechanisms by which GVs alter the level oftranscription. These resources present (1) the human genomeannotation (GENCODE); (2) genome variability in human populations ;(3) GVs associated with diseases ; (4) modificationsof the chromatin ; (5) expression quantitative trait loci; (6) profilingof transcription factor binding events by ChIP-seq ; (7) allele-specific bindingof TFs, identified using ChIP-seq data in combination withthe data on the genotypes of the studied cells ; (8) the effects of genetic variability on TFBSspredicted in silico by computer programs .https://genome.ucsc.edu/) and (2) the genome browser of the Ensembl databasewhich is a joint research project of the European Bioinformatics Institute and the Wellcome Trust Sanger Institute .These genome browsers integrate data on genome sequencesand its features obtained by different research groups usinga wide range of experimental methods . The websites of these browsers provide access tothe primary DNA sequences and genome annotations for manyorganisms . Browser\u2019s graphical interfaces allow to obtain scalablemaps of genomic regions and to visualize interactively a largenumber of annotations and features .A separate category of information resources includes:(1) the genome browser of the University of California, SantaCruz, USA and BioMart data mining tool(https://www.ensembl.org/info/data/biomart/index.html).The websites of the UCSC Genome Browser and EnsemblGenome Browser provide access to software tools for extraction data as text files: UCSC table browser . These approaches are based on the analysis of theChIP-seq data in combination with the sequencing data, whichallow to find heterozygous loci within a single genome and tophase genotypes of the studied cells. Thus, for each type ofcells examined, its own set of genomic loci interacting witha specific transcription factor in an allele-specific mannercan be identified. For example, in , theChIP-seq data for 55 TFs in the HepG2 cells and 57 TFs in theHeLa-S3 cells were analyzed. In HepG2 cells, 3001 genomicloci with allele-specific signals were found, and 712 loci werefound in HeLa-S3 cells. The authors note the pronouncedtissue-specific nature of allele-specific TF binding: of theentire set of identified loci, only 34 were found in both celllines .http://alleleseq.gersteinlab.org/) (see Table 2),as well as in the supplemental files to publications .The data on allele-specific binding of TFs are collected inthe following information resources: AlleleDB http://alleledb.gersteinlab.org/ , AlleleSeq and from 12 to 55 for cancer cell lines .https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php) ,SNP2TFBS , rSNPBase (http://rsnp3.psych.ac.cn/index.do) , rVarBase (http://rv.psych.ac.cn) (see Table 2).When generating hypotheses on the mechanisms that mediate the effect of GVs on disease risk, one can also use the dataon the effects of genetic variants on the functional activity ofTFBSs predicted in silico. Such information is accumulated inspecialized databases: HaploReg :707-715. DOI10.1042/EBC20190030. Beck T., Shorter T., Brookes A.J. 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In general, triatomines are identified by external morphological characters. However, some species are very similar or even morphologically identical, making the use of complementary analyses for the correct identification of species important. For this reason, this study focused on the use of experimental crosses to assess the specific status of species of the Triatoma petrocchiae is a species morphologically similar to T. b. brasiliensis (which resulted in a synonymization event); despite this similarity, genetic, morphological, and experimental crossbreeding studies confirmed the specific status of T. petrocchiae. Considering that both species have been reported living in sympatry and that, for a long time, most species of the T. brasiliensis complex were considered only chromatic variants of T. b. brasiliensis, we carried out experimental crosses between T. b. brasiliensis and T. petrocchiae (to confirm whether these species are reproductively isolated) and between T. lenti and T. petrocchiae . Reciprocal experimental crosses were conducted, and weekly, the eggs were collected, counted, and separated in new containers to assess the hatch rate. Neither cross resulted in hybrids, demonstrating that there are pre-zygotic reproductive barriers installed between T. petrocchiae and the other species of the T. brasiliensis complex. On the basis of the results above, we demonstrated that T. petrocchiae is reproductively isolated from T. b. brasiliensis and T. lenti. Furthermore, we suggest that T. petrocchiae is the species most derived from the T. brasiliensis complex. Trypanosoma cruzi , the etiological agent of Chagas disease [Panstrongylus megistus , Triatoma infestans Klug, 1834, T. brasiliensis brasiliensis Neiva, 1911, T. dimidiata , and Rhodnius prolixus St\u00e5l, 1859 are of worldwide importance in the transmission of the disease [Triatomines are hematophagous insects of great importance to public health, as they are considered the main form of transmission of the protozoan Chagas, 909 .Triatoma Laporte, 1832 is the most representative (81 species) and the most morphologically diversified [T. brasiliensis complex is a grouping of endemic species from Brazil [T. b. brasiliensis Neiva, 1911, T. b. macromelasoma Galv\u00e3o, 1965, T. juazeirensis Costa and F\u00e9lix, 2007, T. sherlocki Papa et al., 2002, T. petrocchiae Pinto and Barreto, 1925, T. lenti Sherlock and Serafim, 1967, T. bahiensis Sherlock and Serafim, 1967, and T. melanica Neiva and Lent, 1941 [T. petrocchiae [The genus ersified ,7. This ersified , and speersified ,10,11,12m Brazil composednt, 1941 ,16,17,18rocchiae ,19; howeT. brasiliensis sensu stricto is currently divided into two subspecies (T. b. brasiliensis and T. b. macromelasoma), which can be differentiated by morphological characters: T. b. brasiliensis presents a pronotum with 1 + 1 brownish-yellow areas extending from the posterior portion of the anterior lobe to the posterior lobe, femora with broad brownish-yellow rings, and membrane of hemelytra with a lumen of cells that are not darkened; T. b. macromelasoma presents a pronotum with 1 + 1 narrow brownish-yellow stripes on the submedian carinae, not attaining its apex, legs with an incomplete brownish-yellow ring on the apical half of the femora, and hemelytra with membrane cells that are darkened on the central portion [T. b. brasiliensis has been noted in the states of Cear\u00e1, Maranh\u00e3o, Para\u00edba, Piau\u00ed, and Rio Grande do Norte, T. b. macromelasoma is endemic to Pernambuco [The species portion . In addirnambuco ,19.Triatoma petrocchiae is a species morphologically similar to T. b. brasiliensis, which led Lucena [T. petrocchiae only as a chromatic variant of T. b. brasiliensis. However, Esp\u00ednola [T. b. brasiliensis and T. petrocchiae from Paulo Afonso, Bahia, Brazil, and observed that these species did not produce viable hybrids. On the basis of this, Lent and Wygodzinsky [T. petrocchiae from morphological data .T. b. brasiliensis from Paulo Afonso, Bahia. The authors indicated that there are similarities in the coloration between T. b. brasiliensis and T. petrocchiae and, above all, these species share the same ecological niche. Considering that these species have been reported living in sympatry [T. brasiliensis complex were still considered only chromatic variants of T. b. brasiliensis, there is a need to confirm whether T. b. brasiliensis and T. petrocchiae are really reproductively isolated .The interspecific crosses performed by Esp\u00ednola were prosympatry ,27 and t hybrids ,30,31,32Esp\u00ednola ) and betT. b. brasiliensis (from Currais Novos (Pedra do Sino), Rio Grande do Norte, Brazil, collected in wild ecotopes (geographic coordinates: 6\u00b017\u203206.8\u2033 S 36\u00b029\u203251.9\u2033 W)) and T. petrocchiae ) and between T. lenti ) and T. petrocchiae . Therop spot ) agree wrop spot when theT. melanica, T. sherlocki, and T. juazeirensis were considered only phenotypic variants and/or subspecies of T. b. brasiliensis [T. petrocchiae, and we observed that only T. b. brasiliensis and T. petrocchiae were the species of the T. brasiliensis complex notified for the municipality [T. brasiliensis complex triatomines collected in Paulo Afonso, Bahia, were correctly identified as T. b. brasiliensis and T. petrocchiae, we evaluated some specimens collected in this municipality that were deposited in the entomologic collections of the Faculty of Public Health of the University of Sao Paulo, Brazil . This r km away , which s hybrids ,30,31,32T. petrocchiae and species of the T. brasiliensis complex was only observed when members of this complex (T. b. brasiliensis) were crossed with other subcomplexes, such as T. sordida [T. infestans [T. vitticeps subcomplexes [T. b. brasiliensis [T. brasiliensis complex is based on post-zygotic reproductive isolation due to hybrid collapse . The a et al. and Aleva et al. ). It was complex ; however complex , the mosT. petrocchiae and all members of the T. brasiliensis complex be carried out to confirm that this species is indeed reproductively isolated from all other species in the complex or whether prezygotic isolation is restricted to T. b. brasiliensis and T. lenti . Furthermore, we demonstrated that these species have prezygotic reproductive isolation and suggest that T. petrocchiae is the species most derived from the T. brasiliensis complex.On the basis of the results above, we demonstrated that"} +{"text": "Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels.ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks.We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3\u00a0million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73\u00d7. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding. Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits in humans and agricultural species , 2. The Low-coverage sequencing (LCS) of a large cohort has been proposed to be more informative than sequencing fewer individuals at a higher coverage rate . Sample Several large-scale WGS projects have been completed . These pIn this study, we developed a new highly accurate, cost- and time-efficient LCS method to obtain high-density single-nucleotide polymorphism (SNP) markers for a large Duroc pig population . By asseA Tn5-based protocol was used to prepare sequencing libraries of each pig at a low cost (reagent cost: $2.60/library) as described in the Methods section. The libraries were sequenced on the Illumina and the BGI platform . The resde novo assembly) , the 948 Program of the Ministry of Agriculture of China (2012-G1(4)), the Science and Technology Innovation Strategy Projects of Guangdong Province [2019B020203002], and the Guangdong Academician Workstation [2011A090700016].X.H., N.L.: conceptualization. X.H., N.L., Y.W., and Z.W.: project administration and supervision. X.H., Y.W., D.Z., X.G., J.R., Z.H., C.B., and R.Y.: methodology, investigation, and formal analysis. R.Y., D.Z., X.G., and Y.W.: data curation and validation. Z.W., G.C., D.L., and C.T.: resources. X.H. and Z.W.: funding acquisition. Y.W. and R.Y.: visualization and original draft preparation. Y.W., X.H., Y.Z., G.C., and D.L.: review and editing."} +{"text": "The correct deployment of genetic programs for development and differentiation relies on finely coordinated regulation of specific gene sets. Genomic regulatory elements play an exceptional role in this process. Thereare few types of gene regulatory elements, including promoters, enhancers, insulators and silencers. Alterations ofgene regulatory elements may cause various pathologies, including cancer, congenital disorders and autoimmunediseases. The development of high-throughput genomic assays has made it possible to significantly accelerate theaccumulation of information about the characteristic epigenetic properties of regulatory elements. In combinationwith high-throughput studies focused on the genome-wide distribution of epigenetic marks, regulatory proteinsand the spatial structure of chromatin, this significantly expands the understanding of the principles of epigeneticregulation of genes and allows potential regulatory elements to be searched for in silico. However, common experimental approaches used to study the local characteristics of chromatin have a number of technical limitations thatmay reduce the reliability of computational identification of genomic regulatory sequences. Taking into account thevariability of the functions of epigenetic determinants and complex multicomponent regulation of genomic elements activity, their functional verification is often required. A plethora of methods have been developed to studythe functional role of regulatory elements on the genome scale. Common experimental approaches for in silico identification of regulatory elements and their inherent technical limitations will be described. The present review is focused on original high-throughput methods of enhancer activity reporter analysis that are currently used to validatepredicted regulatory elements and to perform de novo searches. The methods described allow assessing the functional role of the nucleotide sequence of a regulatory element, to determine its exact boundaries and to assess theinfluence of the local state of chromatin on the activity of enhancers and gene expression. These approaches havecontributed substantially to the understanding of the fundamental principles of gene regulation. The progress of programs for the development and maintenance of body functions is based on the expression of genesets specific to cells and tissues. The gene expression iscoordinated by a multilevel regulatory system that includesgenetic and epigenetic mechanisms based on the interactionof genomic sequences, epigenetic modifications, regulatoryproteins, and specific transcription factors. Certain genomicregions associated with the specific epigenetic determinants,as well as serving as a site for attracting regulatory proteins,are capable of modifying gene expression. Such regulatoryelements in the genome play a key role in the implementationof genetic programs for development, differentiation, andmaintenance of cellular and tissue homeostasis .Dysfunction of genomic regulatory elements may lead tothe development of various pathologies, including cancer,developmental defects and autoimmune diseases . Thegenome wide association studies show that more than 90 %of disease-associated single nucleotide polymorphisms arelocated in non-coding genomic regions . The significant part of the genomicvariants are located in regions that show epigenetic characteristics of enhancers, as well as affect enhancers, specific forthe cell lines involved in the disease pathogenesis . Thegenetic variants associated with the development of type 2diabetes (T2D), which were located in regions of putativeenhancers in pancreatic islets, can be a good example . Today, a lot of information is available regarding thespecific properties of the epigenetic regulatory elementsthat alleviate identification of potential regulatory genomicregions in silico . However, the validationand functional characterization of the regulatory elementsoften requires direct experimental verification. The classicmethods are different modifications of reporter assays andfunctional mutagenesis. With the development of massivelyparallel sequencing methods, methodologies that allow studying the activity of the regulatory elements in genomescale have been developed. This review will describe the existing methodologicalsolutions in the high-throughput analysis of enhancers thathave significantly contributed to the understanding of thefundamental principles of their functions.Several types of genomic regulatory elements, includingpromoters, enhancers, insulators, and silencers are distinguished. Promoters are located near the transcription start siteand serve as a DNA site where the transcription complexis assembled. In eukaryotes, such transcription complexesconsist of the main transcription factors, RNA polymerase,and other regulatory proteins, including those which mediate the interaction with enhancers . Enhancers are nucleotide sequences in genomic DNAthat contain binding sites for transcription factors and cofactors. As part of a protein complex, enhancers can physically interact with the promoter to activate gene expression. Enhancers are able to regulate targetpromoters from a long distance, and regardless of mutualspatial orientation . For example,the ZRS enhancer, the dominant mutation of which leadsto familial forms of polydactyly, is located approximately1 Mb from the controlled Sonic hedgehog (Shh) gene inthe mouse genome . On average, theenhancers are mapped at 20\u201350 Kb from the target gene invertebrate genomes, and at 4\u201310 Kb in the genome of thefruit fly .The regulatory interactions network of promoters andenhancers can be quite complex. A separate gene can shareenhancers with other genes, might be regulated either byseveral enhancers or specific enhancers in different typesof cells. The Arx gene expression, for example, is controlled by four enhancers in mouse brain tissue . Regulation of a gene by specific enhancers isalso observed during the development of pathologies. Forexample, the Myc proto-oncogene enhancer is located intranscription termination sites in case of pancreatic cancer. In case of rectal cancer, it is detected in the 5\u2032-region of thegene, and in case of T-cell acute lymphoblastic leukemia, itcan be found downstream of the 3\u2032-region of the gene . Studies conducted in Drosophila melanogaster haveshown that up to 30 percent of enhancers can act as remoteregulatory elements without affecting the expression ofgenes located between them and target genes . This means that there mustbe fine-tuned regulatory mechanisms that address interaction between the target gene promoter and specific enhancer.Today, there are several functionally intersecting conceptsdescribing mechanics of the promoter-enhancer interactions,the main of which are contact formation via protein homooligomers and chromatin looping, caused by the action ofmotor proteins, such as RNA polymerase II and cohesin. The regulatory elements \u2013 insulators \u2013 play an importantrole in regulation of the chromatin spatial structure. Interacting with specific proteins, insulators are able to blockenhancer-promoter interaction and prevent the distributionof repressive chromatin marks acting as barrier elements. With the development of modern methodsof the nuclear architecture analysis, it became apparent thatthe functional impact of insulators is largely determinedby their participation in the regulation of intra- and interchromosomal contacts . The insulatorproteins play a key role in the formation of topologicallyassociated domain (TAD) . Such fragments are characterized by a high frequency of internalDNA contacts and are often flanked by the binding sites ofinsulator proteins and actively transcribed genes . Along with theregulation of the nucleus spatial structure, insulators areinvolved in many regulatory processes, including activationand repression of the gene expression, alternative splicing,and RNA polymerase pausing . The silencers function is to suppress the gene expression,and such repression is mainly implemented by establishingrepressive chromatin state and competition with activatingproteins .The development of modern methods of high-throughputanalysis has significantly accelerated and simplified thesearch for potential regulatory elements. The assumptionsabout the possible regulatory role of a genomic region areusually based on several types of data, including: (1) DNAaccessibility for regulatory proteins, (2) presence of characteristic epigenetic determinants, (3) evaluation of gene expression and (4) analysis of DNA contacts. Active regulatory elements are associated with specificproteins, and, hence, are free from nucleosomes. The treatment of genomic DNA with DNase I (DNase-seq), micrococcal nuclease (MNase-seq) and Tn5 transposase , followedby high throughput sequencing and FAIRE-seq method, isused to identify such nucleosome-free loci . The listed methods are used for identification of putative enhancers, insulators, and silencers;however, to determine functional class of detected regulatory element, data on DNA accessibility should be combinedwith other descriptive data, e.g. chromatin properties .The genomic mapping of the chromatin characteristicfactors and histone modifications is also used to identifyindividual classes of regulatory elements. The basic methodfor assessing the representation of such epigenetic determinants in a particular genomic region is the chromatin immunoprecipitation followed by massive parallel sequencing(ChIP-seq). Promoters are enriched in H3K4me3 histonemark . Monomethylation at the sameposition of the H3 histone (H3K4me1) is associated withenhancers, and the simultaneous presence of the H3K27me3modification indicates that the enhancer might be poised foractivation, while the H3K27ac modification indicates that theenhancer is active . Enrichment in the p300 histone acetyltransferaseis characteristic of the enhancers . Mapping of specific transcription factors is also used to identifyenhancers. For example, DNA regions enriched by the activeenhancer histone marks, the Mediator complex proteins andthe Oct4, Sox2, Nanog, Klf4, Esrrb master regulators arecalled super-enhancers and control the expression of tissuespecific sets of genes in embryonic stem cells . To identify insulators in vertebrates, the genomicdistribution of the CTCF protein and cofactors involved inthe formation of loops, such as Rad21 and YY, are analyzed.Silencers are enriched by the H3K27me3 histone modification associated with the effect of repressive Polycomb groupproteins, as well as the H3K9me2/3 modifications related toheterochromatin .The spatial organization of the nucleus mediates theinteractions between target genomic loci and distal regulatory elements. The spatial chromatin structure is studied bymethods that allow to fix and analyze DNA-DNA contacts,which originate from the 3C method (chromosome conformation capture) .The most widely used HiC method allows to build DNAgenome-wide contacts map, in contrast to earlier methods.Combinations of chromatin spatial structure analysis andchromatin immunoprecipitation-based methods make it possible to establish DNAcontacts in genomic regions which are specifically enrichedin specific chromatin proteins or histone modifications. Analysis of the DNA-DNA contacts allows identifying promoter-enhancer interactions, defining borders ofthe topologically associating domain and larger chromatincompartments.The data on the epigenetic characteristics and spatialgenomic organization of model objects are available to awide range of researchers in ENCODE, The EpigenomeRoadmap, FANTOM and other databases .These data are widely used for the prediction and researchof potential regulatory elements. However, it must be noted that the methods of analysisof protein-DNA and DNA-DNA interactions are capable ofdetecting non-functional interaction that can result in a falsepositive result. Local enrichment with characteristic epigenetic determinants detected by ChIP-seq does not necessarily indicate the presence of regulatory elements in a specificgenomic region . This can be due to thefact that implementation of the regulatory element functionmight require the coordinated binding of several transcription factors, and binding of only one of them is simply notenough . Nonfunctional transcription factor binding events can betransient, and caused by the general DNA-binding activity. The chromatin immunoprecipitationmethod detects such transient interactions since it is based onthe fixation of chromatin with formaldehyde with the formation of covalent cross-links between DNA and associatedproteins. Modifications of the ChIP method that eliminatethe need for chromatin fixation and potentially improvethe accuracy of the method have been proposed . A micrococcalnuclease fused with protein A is used in the variation of theCUT&RUN method . Protein Abinds with the specific antibodies to the target protein, andmicrococcal nuclease makes DNA breaks in the region ofits binding. This allows selecting short genomic fragments,which are rich in proteins of interest, and identifying themwith high-throughput sequencing. The Tn5 transposase isused in the CUT&TAG method instead of nuclease, whichmakes it possible to simultaneously introduce DNA adaptersfor massive parallel sequencing, flanking the recognition siteof the protein of interest . However,these methods have been developed recently and have notbeen widely used yet.The false positive results in the ChIP-seq experiments mayalso be due to experimental variations, such as chromatinfragmentation mode, sequencing depth, and the thresholdvalues for the identification of binding sites . It is also importantto note that in the presence of high- and low-affinity proteinbinding sites, the ChIP-seq method predominantly detectshigh-affinity ones . This feature is also alimitation of the method, since it was shown that suboptimalbinding sites for transcription factors in enhancers are needed for fine regulation of gene activity during development. In addition to the technical limitations of experimentalmethods, it is important to note that often functional regulatory elements demonstrate the presence of epigenetic determinants, which is generally uncharacteristic for their class.Functionally tested silencers in the K562 and HepG2B cellcultures, according to the ENCODE database, in additionto being enriched with the H3K9me3 and H3K27me3 repressive histone modifications, also contained H3K36me3and H3K79me2 active chromatin histone marks . Due to the experimental limitations of themethods, the variability of the functions of epigenetic determinants, and the participation of many components inthe implementation of the functions of genomic elements,the determination of their regulatory role often requiresfunctional verification. The functional role of genomic regulatory elements is commonly assessed with different modifications of reporteranalysis. Pioneer work where the functional role of the genomic regulatory elements was demonstrated was devotedto the study of the enhancer of the early gene of the SV40virus . This work showed that a DNAfragment from the 5\u2032-end of the early gene of the SV40virus, consisting of two 72 bp repeats, can cause 200-foldactivation of rabbit \u03b2-globin reporter gene expression in theHeLa cells . The standard genetic constructs used for the analysis ofenhancer activity contain a reporter gene under the controlof a minimal promoter, which confers minimal or no expression without additional activation. The genomic sequence ofthe enhancer is cloned into the construct, either upstream ofthe promoter or downstream of the coding sequence of thereporter gene. The obtained construct is used to transformcells and the change in the expression of the reporter genecomparing to a control construct that does not contain apotential enhancer is analyzed. One of the first works aimed at in vivo functional testing of enhancers in genome-wide scale was based on theprinciples of classical reporter analysis .Around 8,000 of the D. melanogaster lines were used,which contained a transgenic construct consisting of potential enhancer, minimal promoter, and Gal4 protein geneintegrated in the same genomic region. The Gal4 expression was assessed at different stages of embryogenesis byin situ hybridization, and 400 embryos at different stagesof development were analyzed for each potential regulatoryelement. As a result, more than three thousand enhancershave been identified. About a quarter were located in thevicinity of regulated genes, and a little more than a quarterwere located at a distance of 20\u2013100 Kb. On average, theywere mapped around 10 Kb from the target genes . About one third of the detected enhancers werelocated in the intergenic regions of regulated genes. Subsequently, it was also functionally confirmed that enhancersare able to regulate not only nearby genes, but also oneslocated through one or two genes . Thedata obtained have significantly expanded the understandingof the fundamental principles of the operation of enhancers;however, the implementation of such projects requires acolossal amount of time and resources. The methods of high-throughput reporter analysis haveevolved from classical approaches and allow simultaneousinterrogation of thousands of regulatory sequences. Thereare two principal approaches in high-throughput reporterassays . Within the first, a reporter gene containsa DNA barcode before the polyadenylation signal, and isplaced under the control of a genomic fragment \u2013 a potential enhancer and a minimal promoter . Inthe case of activation of the reporter gene expression, suchDNA barcode will be contained at the 3\u2032-end of its transcript. After the pooling of such constructs, high-throughput sequencing is carried out, and unique DNA barcodescorresponding to each of the studied genomic fragmentsare determined . After transformation using suchconstructs, the presence of DNA barcodes is analyzed bythe transcriptome sequencing (RNA-seq). The expressionlevel of a particular DNA barcode allows to assess activatingability of the corresponding specific regulatory element. Thisapproach is used in the methods of quantitative assessmentof the activity of genomic fragments, called MPRA , different variations of which willbe covered in this review .The second approach allows evaluating the qualitativeability of the genomic fragment to exhibit the enhancers\u2019properties. At first, a pool of genetic constructs that containthe genomic fragment of interest, a minimal promoter, and areporter gene encoding a fluorescent protein or luciferase isprepared. At the next stage, the obtained pool of constructs isused for transformation and cells expressing the fluorescentprotein are sorted using flow cytometry. The activation of thereporter gene expression means that the genomic fragmentof interest demonstrates enhancer activities. The sorted cellsare subjected to DNA isolation, fragments of constructs corresponding to the studied genomic fragments are amplified,and massive parallel sequencing is carried out, thus allowing to identify specific genomic fragments exhibiting theproperties of enhancers. Examples of such methods includeFIREWACh and SIF-seq . Combinations of the two approaches described above arealso used. In this case, at the first stage cells carrying constructs containing potential enhancers are selected by flowcytometry. Then, the activating ability of specific genomicfragments is quantified by analyzing the representation ofDNA barcodes by the RNA-seq method . MPRA methods are successfully used to study the activating properties of the nucleotide sequence of enhancers, the functional influence of regulatory protein bindingmotifs, and to search for and validate enhancers. Using thismethodology, the effect of single mutations in the composition of three enhancers \u2013 ALDOB, ECR11, and LTV1,active in liver cells, was studied .In the course of this research, a DNA library containingmore than 100,000 mutated variants of the enhancers wassynthesized. Such DNA fragments were cloned into constructs containing the minimal promoter, luciferase geneand transcribed DNA barcodes. The resulting DNA libraries were injected into the liver of mice, and a day later thetranscriptome of liver cells was analyzed by RNA-seq .It was found that the majority of single mutations hada weak effect on the activity of the studied enhancers. Inaddition, it was shown that mutations disrupting the enhancer function affect the predicted binding sites of theHNF4 and HNF1 transcription factors, which are active inliver cells . It is important to note that theexperiment also showed significant discrepancies in theoryand practice. Thus, within the ECR11 enhancer, mutationscausing functional disorders were concentrated in the regionthat did not contain predicted binding sites for transcriptionfactors, while mutations in the region containing most ofthese predicted sites did not change the enhancer activity.On the one hand, this clearly demonstrates that MPRA areapplicable to clarify the boundaries of enhancers, and on theother hand, it emphasizes the importance of experimentalverification of predictive data.MPRA are also used for de novo search and validationof predicted enhancers. An elegant approach to search forenhancers was implemented in the STARR-seq method . The authors used theability of enhancers to activate expression regardless of theposition relative to the gene and promoter, and developedreporter constructs, containing studied genomic fragmentscloned into open reading frame downstream from minimalpromoter. In case a genomic region exhibits an enhancerfunction, this will lead to its transcription in cells. Theexpression level of this fragment in the cell transcriptomemakes it possible to assess its activating function. This approach completely eliminates the need to use DNA barcodes,since the fragments play that role themselves. To seek for enhancers, a plasmid library containingmillions of random fragments of the fruit fly genome wasprepared. After transfection of the S2 cell culture, a highthroughput RNA-seq transcription profile analysis was performed. As a result, thousands of genomic fragments wereidentified, which demonstrated the properties of enhancers.The most active were located close to housekeeping genesand developmental transcription factors. About a third of thefragments demonstrating pronounced activating properties inthe S2 cell genome were located in areas of closed chromatin,lacking H3K27ac mark of active enhancers. Thus, it seemsunlikely that such fragments are capable of performing the role of enhancers in the genome of the studied cells, andthis finding highlights some of the limitations of episomalMPRA, which will be discussed below.An interesting modification of the STARR-seq methodwas used in a subsequent work on the study of enhancersin human embryonic stem cells . Inthe original work, DNA libraries were obtained by ultrasonic fragmentation of the D. melanogaster genomic DNAand subsequent mass cloning of the obtained fragments. However, this approach is poorlyapplicable to larger genomes, since a sufficient representation of regulatory elements in the resulting DNA librariesis an extremely difficult task to achieve. Indeed, the use ofthe original STARR-seq method to study the regulatoryelements of the mouse genome will require the creationof more than 200 million unique constructs . Experimental verification showed that the use of aplasmid library containing 1.3 million unique fragmentsof the human genome made it possible to identify only sixenhancers .To overcome this limitation, the ChIP-STARR-seqmethod was proposed. In the original paper, the chromatinimmunoprecipitation was used to isolate genomic fragmentsenriched with the OCT4, NANOG transcription factors, aswell as the H3K4me1 and H3K27ac histone modifications. Obtained DNA fragments were thencloned into DNA libraries similar to those used in the original method. It was found that only a part of the genomicfragments that demonstrate enrichment by these factors ingenome exhibited enhancer activity. Only about 25 % of thefragments bound by OCT4 showed enhancer properties. Forthe fragments enriched in NANOG and the H3K4me1 andH3K27 histone modifications, the results were 15, 9, and10 %, respectively. It has been shown that neither individualfactors nor their combinations are capable of unambiguouslypredicting enhancers. In addition, a group of enhancers associated with the regulation of general cellular processes,which had not previously been found in ESCs, were found.It turned out that such enhancers demonstrate a ratherweak enrichment in TF OCT4 and NANOG, as well as inthe histone modification H3K4me1, and, most likely, forthis reason they were not previously detected in prospecting studies based on the chromatin immunoprecipitationmethod. Data on chromatin accessibility and the genomic distribution of histone modifications and regulatory proteinsdeposited in open repositories allow to predict regulatoryelements. Using MPRA, the activity of regulatory elementsin the K562 cells and the E1 human embryonic stem cells,identified on the basis of chromatin structure analysis andannotated in ENCODE, was studied . It turned out that only about a quarter of them had aneffect on gene expression, which underlines the importanceof such experimental verification .At the same time, this effect may be due to the experimentallimitations of the described MPRA. Indeed, the methodsdescribed above are episomal, which means that reporterconstructs are not integrated into the genome, hence the activity of enhancers is assessed outside the chromatin context.Significant differences in the activity of enhancers analyzedin episomal manner and upon integration into the genomewere also confirmed experimentally .This experimental discrepancy looks logical, becausethe observation of the effect of chromatin structure ongene regulation was demonstrated in classical genetic experiments long ago . The use of an originalhigh-throughput reporter analysis method, combined withMPRA-approaches, made it possible to characterize the localeffects of chromatin on gene expression in mouse embryonicstem cells . Within theframework of this study, using the PiggyBac transposasebased genomic integration system, reporter constructs containing unique DNA barcodes at the 3\u2032-end of the reportergene were randomly inserted into the cell genome.In the next step, such insertions were mapped and eachDNA barcode was associated with a specific genomic locus.In total, more than 17 thousand of such inserts were received.Then, the expression level of DNA barcodes was analyzedusing the RNA-seq method, which made it possible to assess the transcriptional activity of each insertion as well asthe effect of the local chromatin structure on it. Reporterconstructs integrated into regions of compacted chromatinand regions of domains associated with the nuclear lamina,as expected, showed a reduced level of expression. Reporterconstructions located within 200 Kb from active genes weremore actively transcribed. It is interesting to mention thatan increased frequency of enhancers was observed withinapproximately the same range. Enhancers had an activatingeffect on the expression of reporter constructs at a distanceof up to 20 Kb. It is important to note that in this case alinear distance is considered, and the spatial structure ofchromatin is not taken into account. It was assumed that theformation of extended, actively transcribed regions is basedon the action of several enhancers. This emphasizes theneed to study regulatory elements in conditions close to native ones.The effect of chromatin on the function of regulatoryelements is to some extent taken into account in MPRA,which are based on the genomic integration of the reporterconstruct . These FIREWACh and SIF-seq methodswere used to identify enhancers in mouse ESCs, but did notallow quantitative assessment of the activity of regulatoryelements .The FIREWACh method is based on genomic integration of reporter constructs using lentiviral transduction. This method of genomic integration ensuresthe insertion of the construct into random regions of thegenome . Thus, an adequate comparisonof the activity of various regulatory elements seems to bedifficult, because it is highly likely that reporter constructs will be integrated into different genomic regions, with anunpredictable effect of the local chromatin environment. The SIF-seq method avoided such a drawback, sincethe integration of reporter constructs is carried out in thesame region of the genome located in the region of theHprt gene . However, thismight serve as a disadvantage, since the correct operationof an enhancer is determined by a specific set of chromatinfactors, and it is highly likely that it will become non-functional when transferred to a non-identical chromatin environment.The approaches described above did not allow answering one of the fundamental questions of understanding theprinciples of enhancers\u2019 activity, namely, to what extent is itdetermined by the DNA sequence, and to what extent \u2013 bythe properties of the surrounding chromatin? A systematicstudy of this issue was carried out in the research on theinfluence of different chromatin environments on the comparative activity of enhancers . Withinthe framework of this study, 15 lines of the K562 cells wereprepared, containing single insertions of reporter constructslocated in different chromatin environments and containing the Cre-recombinase (loxP) recognition sites, allowingtargeted insertion of transgenes. Such insertions containeda DNA barcode and a polyadenylation signal outside of thefragment flanked by loxP-sites, with a single unique DNAbarcode corresponding to each line. The described lines were pooled together, and Cre-mediated integration was used to integrate reporter constructs,that contained a reporter gene ending with a DNA barcodeunder the control of the minimal promoter and the genomicfragment of interest. As such fragments, 300 synthesizedregulatory elements were used, which were previouslystudied by episomal MPRA and ranked according to thelevel of activity . For each genomicfragment, the corresponding unique DNA barcodes had beenpreviously established. In case of successful integration, theoriginal loxP cassette was replaced with a reporter constructcontaining the putative enhancers. Moreover, in the case ofactivation of the reporter gene, two DNA barcodes will betranscribed in its composition. Deciphering barcodes allowsto identify which fragment was analyzed in which cell line.The analysis of the representation of combinations ofDNA barcodes in the transcriptome of cells made it possible to assess the level of activity of the studied regulatoryelements in different chromatin environments. It was foundthat the chromatin environment has pronounced effect onthe activity of cis-elements. However, being placed in thesame chromatin environment, regulatory elements save theirrelative activity. It was also demonstrated that the activity ofthe promoter affects the expression of reporter constructs, butat the same time does not affect the comparative activity ofregulatory elements. The results obtained support the modelaccording to which the nucleotide sequence of the enhancerdetermines its overall activity, which is already modulatedby the structure of the chromatin environment. MPRA methods allow to perform detailed study of theregulatory potential of the genomic fragments, and it is aconvenient tool for studying the effect of variations in thenucleotide sequence on their function. However, it is necessary to note the limitations of the methods, which should betaken into account when interpreting the results obtained.The common drawback of MPRA is the need to use a minimal promoter that is unable to activate the expression ofthe reporter gene in the absence of an enhancer, since thepresence of basal activity can significantly distort the results.At the same time, the selected promoter can significantlyinfluence the activity of a particular enhancer . In this sense, the analysisof the activity of enhancers in combination with variouspromoters seems to be an ideal experiment. However, suchwork seems to be extremely difficult and time-consumingThe synthesis of DNA fragments used as studied regulatory elements imposes restrictions on the total length of sucha fragment. Usually, the length of the studied fragments islimited to about 200 bp, which often complicates the analysisof the influence of the rest of the enhancer regions fallingoutside these limits . MPRA methods based on episomal constructs do not take into accountthe possible influence of the chromatin environment on theregulatory element; therefore, they can be used to study thedirect activating ability of a DNA sequence. MPRA basedon the genomic integration of reporter constructs make itpossible to overcome this limitation to some extent. However, random or site-specific integration still does not allowthe analysis of the activity of a regulatory element in nativegenomic environment. The impossibility of studying theenhancers function in native environment is a serious MPRAlimitation, since the function of the regulatory genomic element depends on the structure of the surrounding chromatinand the spatial organization of the locus.Modern methods of high-throughput CRISPR/Cas9mutagenesis, as well as methods of directed expressionmodulation based on the use of an inactivated form of theCas9 endonuclease (dCas9) fused with activator or repressorproteins, make it possible to study regulatory elements innative genomic environment . While thereare obvious advantages, such methods also have potentialdrawbacks. For example, point mutations produced bythe targeted mutagenesis may not be sufficient to disruptenhancer function. In addition, directed mutagenesis isassociated with errors in the recognition of target genomeregions (off-targets), which can lead to the generation ofexperimental noise. It is important to note that the KRAB repressor protein,which is widely used for the targeted inactivation of enhancers, is capable of initiating the formation of heterochromatin regions of 1\u20132 Kb in length .This feature can reduce the resolution of the method andcomplicate the identification of specific functional fragments of the enhancer, as well as increase unwanted side effectsin the case of the presence of erroneous dCas9 recognitionsites. In addition to possible technical difficulties, in thecase of a successful disruption of the enhancer function,phenotypic manifestations can be restored rather quicklydue to the presumable existence of duplicate enhancers.Thus, MPRA and high-performance methods based onthe CRISPR/Cas9 system are quite complementary andmake it possible to characterize in detail the regulatoryfunctions of the studied genomic fragments. 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On the other hand, free-living flatworm species, evolutionarily close toparasitic flatworms, do not have the abovementioned difficulties, which makes them potential alternative modelsto search for and study homologous genes. In this review, we describe the use of the basal free-living flatwormMacrostomum lignano as such a model. M. lignano has a number of convenient biological and experimental properties, such as fast reproduction, easy and non-expensive laboratory culturing, optical body transparency, obligatorysexual reproduction, annotated genome and transcriptome assemblies, and the availability of modern molecularmethods, including transgenesis, gene knockdown by RNA interference, and in situ hybridization. All this makesM. lignano amenable to the most modern approaches of forward and reverse genetics, such as transposon insertional mutagenesis and methods of targeted genome editing by the CRISPR/Cas9 system. Due to the availability ofan increasing number of genome and transcriptome assemblies of different parasitic flatworm species, new knowledge generated by studying M. lignano can be easily translated to parasitic flatworms with the help of modernbioinformatic methods of comparative genomics and transcriptomics. In support of this, we provide the results ofour bioinformatics search and analysis of genes homologous between M. lignano and parasitic flatworms, whichpredicts a list of promising gene targets for subsequent research. Hundreds of millions of people worldwide are infectedby various species of parasitic flatworms . The highest frequency of infections, as well the mostsevere pathologies, are induced by the species of the classTrematoda, or liver flukes, which cause such well-knowndiseases as schistosomiasis, clonorchiasis, and opisthorchiasis. Characteristic severe effects of the liver flukesinfections are acute and chronic inflammation of liver andbiliary tract, which can develop into liver fibrosis and cholangiocarcinoma, respectively . Infections of anotherclass of parasitic flatworms, Cestoda, or tape worms, oftendo not lead to such severe pathologies and death, but in thelong-term perspective and without treatment they can lead tosignificant aberrations in vital activity and as a consequencea decrease in life quality of sick people .In the world, for more than 40 years praziquantel and itsderivatives have been the \u201cnumber one\u201d drugs against helminthiases . However,continuous and widespread use of praziquantel has alreadyresulted in the increasing number of reports on emergingresistance to the drug in different species of helminthes. An induced resistance to praziquantel was experimentally demonstrated insome schistosomes . Inital successesof praziquantel slowed down investments into the development of new anthelmintic drugs, which further complicatesthe situation. At the same time, the developed alternativesto praziquantel demonstrate analogous or sometimes evenlower efficiency, more side effects, and usually are effective only against certain trematode species . Therefore, there is an urgent need for new and moreeffective anthelmintic drugsParasitic flatworms have complex life cycles with severalchanges of the hosts , are laborious and expensive in laboratory culturing,and have numerous specific adaptations that complicate theirstudy by standard molecular techniques. All these properties,undoubtedly, slow down fast development of new anthelmintic drugs. Our knowledge on a broad spectrum of biologicalquestions was gained via research on convenient model organisms, such as nematodes, fruit flies, mice, yeast, etc.Similarly, studies of free-living animals help to obtain newinformation about their parasitic relatives. For example,investigating model free-living roundworm (nematode)Caenorhabditis elegans, new data were obtained, whichallowed description of a more detailed mechanism of action for some anti-nematode drugs, as well as helped thesearch for new genes potentially regulating the life cycleof parasitic nematodes. Subsequently, these genes can beused as targets for developing new drugs .Among flatworms, free-living species can be used as models to screen for new drugs directed against their parasiticrelatives . Despite fundamentaldifferences in the life cycles, free-living flatworms have aset of evolutionary conserved properties of their physiologyand reproduction, which are shared with parasitic species.In this study, we describe the properties, advantages, andpotential application of the free-living flatworm Macrostomum lignano as a convenient research model for efficientscreening of conserved genes homologous to the genes ofparasitic flatworms, which can serve as targets for the development of new anthelmintic drugs. Macrostomum lignano is a free-living flatworm from a basal (the earliest branching) clade \u2013 Macrostomorpha . M. lignano can easily tolerate awide range of different environmental conditions, such astemperature, salinity, and oxygen concentration . It wasexperimentally demonstrated that the worms can surviveat the temperatures between 4 to 37 \u00b0C . M. lignano is easy to culture in laboratory conditions. The size of adult animals variesfrom 1 to 3 mm in length and 0.3 mm in width. Worms aremaintained in Petri dishes with artificial sea water. A speciesof unicellular diatom algae Nitzschia curvilineata, which isitself easy to culture in laboratory conditions under artificialillumination, is used as food source. In one standard (9 cm)Petri dish, 500\u2013600 individuals can be easily simultaneouslymaintained. Standard cultivation temperatures are 20 \u00b0C and14/10 hours day/night light cycle.Free-living flatworms are famous for their high regeneration capacity . The known champions are planarians, which can restore a full-grown animal from just afew cells . M. lignano is nearly asregenerative as planarians, and can fully regenerate its bodyposterior from the pharynx and anterior to the brain . Flatworm regeneration comes from divisionand differentiation of somatic stem cell population calledneoblasts . Neoblasts and their differentiating progenitors are the only dividing cells in flatworms,and, apart from regeneration, they are also responsible forthe natural tissue renewal during homeostasis . Importantly, there are alsoneoblast-like cells in parasitic flatworms, which are morphologically similar to neoblasts described in free-livingspecies . Neoblast-like cells candifferentiate into other cell types and are responsible forregeneration of lost body parts in parasitic flatworms, aswell as have similar transcriptional profiles to neoblasts fromfree-living species. Thus, there is an obvious homology ofcentral systems of homeostasis and regeneration betweenfree-living and parasitic flatworms.An important advantage of M. lignano compared to otherpopular free-living model flatworms \u2013 planarians \u2013 is itsbody transparency . This substantially facilitates morphological studiesof its internal structures with the help of light microscopy.M. lignano is an obligatory reciprocal hermaphrodite,favorably distinguishing it from planarians, which inlaboratory conditions reproduce predominantly asexuallythrough fission, and are also genetically mosaic even withinan individual .Obligatory sexual reproduction of M. lignano allows itsapplication in controlled genetic studiesCurrently, the presence of a simple and efficient methodfor transgenesis is the unique feature of M. lignano amongother flatworm species . M. lignanolays 1\u20132 single cell eggs per day. Eggs are large (~100 \u03bcm),have relatively hard shells, and can be easily manipulatedwith the help of plastic microtools. These properties allowedthe development of a successful protocol for delivery ofvarious genetic constructs insidethe eggs by means of microinjection . To date, there is a range of M. lignano transgenic lineswhich express genes of reporter green and red fluorescentproteins in different organs and tissues, allowing to studythe place and dynamics of expression of a gene of interestin vivo . Apart from transgenesis, other classical molecular andcytological methods are successfully applied in M. lignano.Localization of a gene of interest expression can be studied by means of in situ hybridization . To identify gene function, there is a very simple and efficient protocol for knockdown of gene expression byRNA interference, and there is no need for special deliveryof double-stranded (dsRNA) constructs \u2013 worms are simplysoaked in dsRNA solution and after 1\u20133 weeks, due to thetransparency of M. lignano, it is possible to observe occurredmorphological, physiological, or behavior changes . Thus, the available experimental methods allowimplementation of complex studies on the expression andgene function in M. lignano.Any modern model organism needs a well-assembledgenome and transcriptome assembly with annotation ofgenes and repetitive sequences, transposons and simple/tandem repeats. M. lignano is not an exception . M. lignano has a relatively compactgenome of ~500 Mb. Genome and transcriptome assembliescan be openly accessed and viewed using the convenientweb-interface http://gb.macgenome.org/ . We already know genesthat are differentially expressed specifically in neoblasts andthe worm germline . Thus,M. lignano can be used for computational analysis of evolution, comparative genomics and transcriptomics to search forconserved genes homologous to parasitic flatworms. Mainproperties of M. lignano, planarians, and parasitic flatwormsare summarized in the Table.Development of acute and chronic inflammation is an important hallmark of trematode-caused pathologies, which arecaused by constant egg laying of the parasites, leading tothe activation of the immunological response, which is especially relevant to schistosomiasis . Thus, the germline of helminthsand genes that control its development and homeostasis appear as promising targets for the development of new drugsdirected to suppress their expression. In a recent work on M. lignano it was shown that the majority of its genes classified asgermline-specific are flatworm-specific (both for free-livingand parasitic species) and lack a homolog in human andother model organisms. Investigation of flatworm-specificgenes can be the key to search for new anthelmintic drugswith fewer side effects due to their target action on the geneproducts absent in humans. M. lignano is a convenientmodel to screen for such targets. As mentioned earlier, allorgans of its reproductive system are clearly distinguishable under a common light dissecting microscope. Thissignificantly facilitates the screening of phenotypes linkedto the disruption of genes active in gonads and/or copulativeorgans . Importantly, the worm hermaphroditism will allow maintaining in populationsgenetic aberrations linked to the activity of either male orfemale reproductive systems. Disturbances in fertility willalready be detectable within a week at 25 \u00b0C , which will help not to miss mutations in theabsence of a clear morphological phenotype.Now we are already at the beginning of the era of targeted genome editing that started with the wide spread ofCRISPR/Cas9 technology . Given awell-annotated genome assembly, it is possible to introducemutations to a certain gene of interest, which would leadto complete disruption of its function (knockout) . Of particular interest is insertion of markerreporter sequences (e. g. fluorescent proteins) directly inthe open reading frame of a target gene (knockin), whichallows direct visualization of the gene expression patternby the localization of the encoded protein . For example, by combininglabeling of several proteins by different fluorescent proteins,interactome studies are possible. The function of CRISPR/Cas9 depends on only two (in thecase of knockouts) or three (in the case of knockins) components: guide RNA, Cas9 nuclease protein, and a matrixfor homologous recombination. In the simplest scenario,these are two plasmid vectors, one of which encodes guideRNA and Cas9, and the other is the matrix for homologousrecombination . Alternatively, this canbe a combination of in vitro synthesized guide RNA andCas9 in the form of mRNA or Cas9 protein in the complexwith the guide RNA, which eliminates the possibility forunwanted insertion of the plasmid vector . Successful and reproducible applicationof CRISPR/Cas9 is impossible without an efficient delivery of genetic constructs . Currently,M. lignano is the only flatworm for which this is possibleby means of microinjection into single-cell stage eggs ofthe worm . Such an approach iscertainly the most effective, since all the components of thesystems are delivered simultaneously in the required molarratio at the single-cell stage, which decreases chances formosaic progeny. Although currently there are no publisheddata on the application of CRISPR/Cas9 in M. lignano, ourpreliminary experiments show that this approach can be efficiently applied for a knockin introduction in the M. lignanogenome.Studies of phenotypes after targeted disruption/labelingof a gene of interest are characteristic of reverse geneticsmethods . The main disadvantage ofthis approach is that a high-quality assembly and the annotation of the genome are required for the correct selectionof the modification site and the preliminary assessment ofthe gene function based on its homology to already knownproteins . Moreover, genome editingby CRISPR/Cas9 depends on how frequently a GG patternoccurs in the genome, as the Cas9 protein must first detecta PAM-site (Protospacer Adjacent Motif) NGG in the targetsequence . An additional problem is thatdifferent guide RNAs vary significantly in their efficiencyof double-strand break induction, and it is rarely possibleto exactly predict the efficiency during the in silico design. While classical models, such as humancell lines, mouse, Drosophila, the nematode C. elegans, andyeasts are thoroughly studied and there are enough data ontheir gene function to predict a phenotype, and their genomicGC-content is optimal, the situation with alternative modelsis different.The function of a gene is rarely known, as it can be conserved only within a certain evolutionary taxon (e.g. thecase of flatworm germline-specific genes). The genome canhave a low GC-content, less than 40 %, which lowers theprobability to meet a GG in the target regions that could bemutated to result in the target gene knockout . In such cases, one should follow a historicallyearlier approach of forward genetics: from a phenotype tothe gene . Transposon insertional mutagenesis is the most developedtool among the methods of forward genetics. Compared tochemical mutagens, which induce mutations throughout thegenome but require significant time to map the mutation, atransposon movement and its insertion place can be easilydetected by modern methods within one-two days . This is achieved because the transposon sequence is originally not present in the studied genome;various promoters, enhancers, and gene trapping reporterconstructs can be put in the transposon to additionally reporton its insertion as well . In a recent study on the malariaparasite, it was transposon mutagenesis using the piggyBac DNA transposon that allowed to create 38,000 mutants ofthe plasmodium, and in these mutants 2680 genes regulatingthe parasite reproduction in blood cells were identified . The authors note that it was not possibleto apply CRISPR/Cas9 due to anomalously low GC-content(< 20 %) of the plasmodium genome. M. lignano and otherflatworms, including parasitic ones, are now far from beingclassical and ubiquitously used model objects. As mentionedabove, genes specific to the germline of flatworms mostlylack a homolog in other animals, eliminating the predictivepower of the reverse genetics methods. Thus, transposonmutagenesis appears to be the most promising approach tosearch for the genes regulating flatworm germline, as wellas other flatworm-specific genes controlling other functions,and the development of an efficient protocol for transposonmutagenesis in M. lignano is warrantedImportantly, new knowledge gained from experiments onM. lignano can be transferred to parasitic flatworms due toavailability of numerous assemblies of genomes and transcriptomes for the most significant parasitic species, whichare accessible at the WormBase ParaSite (https://parasite.wormbase.org/index.html) database . By using modern computational tools of comparative genomics and transcriptomics, it is possible to readilyidentify the sequences of potential target genes revealedin M. lignano, which are homologous in different parasiticflatworm species, and to perform their comparative andphylogenetic analyses in silico. This will allow to selectcandidate genes that will be the most conserved throughoutall parasitic flatworm genomes, and (preferably) have weakhomology to human genes.1.From the WormBase ParaSite database, amino acid sequences of protein-coding genes from 31 parasitic flatwormspecies were retrieved: 14 species from the class Trematoda,15 species from Cestoda, and 2 species from Monogenea1 Supplementary materials 1\u20132 are available in the online version of the paper:http://www.macgenome.org/download/pdf/Ustyantsev_2021/In this study, we highlighted the key properties of free-livingflatworm M. lignano as a model organism, and those thatmake it a promising object for fast and efficient screeningof potential anthelmintic drugs. 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This has also been corrected on the publisher's website.The originally published version of this paper showed an error in"} +{"text": "Scientific Reportshttps://doi.org/10.1038/s41598-021-84070-7, Published online 25 February 2021Correction to: Nina Khanna, Enos Bernasconi, Matthias Cavassini, Huldrych F. G\u00fcnthard, Christian R. Kahlert and Andri Rauch were omitted from the author list in the original version of this Article.The Author contributions section now reads:\"E.Z. and J.F. conceived and supervised the work. S.R. and C.H. performed the association analyses. D.P.D., S.M. and J.B. performed EBV sequencing and curated the data. A.L. prepared and analysed the viral sequencing data. P.J.M., D.L. and O.N. contributed to the design of the work. N.K, E.B., M.C., H.F.G., C.R.K. and A.R. recruited the study participants and collected the samples and associated data. S.R., C.H., A.L. and J.F. wrote the paper. All authors reviewed the manuscript and approved the submission.\u201dFurthermore, the original version of this Article contained typographical errors in the spelling of Huldrych F. G\u00fcnthard and Christian R. Kahlert, which were incorrectly given as Huldrych G\u00fcnthard and Christian Kahlert respectively.This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file."} +{"text": "Camellia chrysanthoides H. T. Chang and Camellia achrysantha H. T. Chang et S. Y. Liang are two threatened yellow camellia species endemic to southwestern Guangxi, China. Here, we report the complete chloroplast (cp) genomes of C. chrysanthoides and C. achrysantha for the first time. The total cp genome of C. chrysanthoides is 156,959\u2009bp and contains a large single-copy region, a small single-copy region, and a pair of inverted repeat regions. The cp genome of C. achrysantha is 156,658\u2009bp and includes an LSC region of 86,249\u2009bp, SSC region of 18,243\u2009bp, and two IR regions of 26,083\u2009bp each. Both C. chrysanthoides and C. achrysantha have 136 genes, including 93 protein-coding genes, 35 tRNA genes, and eight rRNA genes. Camellia chrysanthoides H. T. Chang and Camellia achrysantha H. T. Chang et S. Y. Liang (family Theaceae) have yellow flowers and are endemic to southwestern Guangxi, China. C. chrysanthoides grows exclusively in acidic soils and has a narrow distribution in Longzhou County genomes of C. chrysanthoides and C. achrysantha to provide genetic data to support the conservation and utilization of these two rare species.ty Chang . It has ty Chang . C. achrng Liang . C. achrC. chrysanthoides and C. achrysantha were collected from Daqing Mountain, Longzhou County, Guangxi, China and Tuolu Town, Chongzuo, Guangxi, China , respectively. Voucher specimens of C. chrysanthoides and C. achrysantha were deposited at the Herbarium of Guangxi Institute of Botany under the voucher numbers IBK00430874 and IBK00430873, respectively. Genome sequencing was conducted on the Illumina NovaSeq 6000 Platform. Approximately 5.2\u2009Gb of C. chrysanthoides and 5.3\u2009Gb of C. achrysantha raw reads were obtained. After filtering the low-quality data, \u223c5\u2009Gb of clean data were yielded for each species. The trimmed reads were assembled by NOVOPlasty .Fresh leaves of C. chrysanthoides was 156,959\u2009bp in length with a GC content of 37.3%; it had a typical four-conjoined structure: a large single-copy (LSC) region of 86,564\u2009bp, a small single-copy (SSC) region of 18,267\u2009bp, and two inverted repeats (IR) regions, each of 26,064\u2009bp. A total of 136 genes were annotated, including 93 protein-coding genes (PCGs), eight ribosomal RNA (rRNA) genes, and 35 transfer RNA (tRNA) genes. The complete cp genome of C. achrysantha was similar, with a total length of 156,658\u2009bp (37.3% GC content), including an LSC region of 86,249\u2009bp, SSC region of 18,243\u2009bp, and two IR regions of 26,083\u2009bp each. It contains 136 genes, including 93 PCGs, eight rRNA genes, and 35 tRNA genes.The complete cp genome sequence of C. chrysanthoides, C. achrysantha, and other cp genome sequences of Camellia. Polyspora axillaris was used as the outgroup. The GenBank accession numbers of the sequences used in this paper are given in C. chrysanthoides was clustered with C. mingii and C. liberofilamenta with 72% bootstrap support (C. achrysantha was closely related to C. indochinensis with 99% bootstrap support (Camellia require protection.Phylogenomic analysis based on the complete cp genomes was performed using support . C. achr support . Future"} +{"text": "Scientific Reports 10.1038/s41598-021-04103-z, published online 10 January 2022Correction to: The original version of this Article contained an error in the spelling of the author Seyedeh Fatemeh Sadeghian Motahar, which was incorrectly given as\u00a0Seyedeh Sadeghian Sadeghian Motahar.The Author contributions statement now reads:\u201cS.H.M., S.F.S.M. and A.S.A.M. carried out the experimental procedures. M.S. contributed in data analysis and interpretation. K.K. performed bioinformatic analysis. S.A. and G.H.S. designed the study and helped with data interpretation and discussion. All the authors wrote and reviewed the article.\u201dThe original Article has been corrected."} +{"text": "Scientific Reports 10.1038/s41598-018-21834-8, published on 22 February 2018Correction to: Peter Q. Nguyen was omitted from the author list in the original version of this Article.The Author Contribution section now reads:\u201cA.D.-T. and N.S.J. conceived the idea and designed the experiments. A.D.-T., and P.P. conducted all experiments and data analysis. T.N. and F.W. cloned the TFF variants. P.Q.N. designed and provided template for the flexible linker. The manuscript has been approved by all the authors.\u201dThe original Article has been corrected."} +{"text": "CLE (CLV3/ESR) is one of the most important groups of peptide phytohormones: its members regulate the development of various plant organs and tissues, as well as interaction with some parasites and symbionts and response to environmental factors. In this regard, the identif ication and study of the CLE genes encoding the peptides of this group in cultivated plants are of great practical interest. Relatively little is known about the functions of CLE peptides in potato, since the CLE genes of the potato Solanum phureja Juz. et Buk. were characterized only in 2021. At the same time, potato includes plenty of tuberous species of the genus Solanum L., both wild and cultivated, and the diversity of its forms may depend on differences in the sequences of CLE genes. In this work, we performed a search for and analysis of the CLE gene sequences in three wild potato species and four cultivated species . In total, we identif ied 332 CLE genes in the analyzed potato species: from 40 to 43 genes of this family for each potato species. All potato species taken for analysis had homologues of previously identif ied S. phureja CLE genes; at the same time, the CLE42 gene, which is absent from the S. phureja genome, is present in all other analyzed potato species. Polymorphism of CLE proteins of S. commersonii is signif icantly higher than that of other analyzed potato species, due to the fact that S. commersonii grows in places outside the growing areas of other potato species and this potato is probably not one of the ancestors of cultivated potato. We also found examples of polymorphism of domains of CLE proteins that carried different tions. Furtherstudy of potato CLE proteins will reveal their role in development, including regulation of productivityin this important agricultural crop. The growth and development of higher plants, as well as theirresponse to external stimuli, are regulated by intercellularcommunications mediated by phytohormones. In additionto the well-known and thoroughly studied \u201cclassical\u201d planthormones , numerous familiesof peptide hormones, which are mobile secreted oligopeptidesor small proteins, play an important role in the coordinationof plant development . One of themost famous families of peptide phytohormones with diversefunctions is the family of CLE (CLV3/ESR) peptides. Thesepeptides got their name from the first identified representatives:the CLAVATA3 (CLV3) Arabidopsis peptide and the ENDOSPERM SURROUNDINGREGION (ESR) maize peptide .Nowadays, genes encoding CLE peptides have been identifiedin all groups of terrestrial plants, as well as in the greenalga Chlamydomonas reinhardtii .CLE genes encode proteins 100\u2013150 amino acids (AA)long, which have a signaling domain (SD) at the N-terminus,a conserved CLE domain at the C-terminus, and a variabledomain (VD) between them . TheCLE domain, consisting of 12 AAs, is a functional part of theCLE protein: immediately after synthesis, the precursor proteinundergoes proteolytic processing and post-translationalmodifications . As a result,what remains of it is the CLE domain with modifications of conservative proline residues;this is the mature CLE peptide. CLE peptides that aresecreted into the intercellular space become ligands for receptorkinases of Leucine Reach Repeats containing Receptor-Like Kinases (LRR-RLK) families and CRINKLY4 that arelocated on the plasma membranes of cells . By interacting with receptors, CLE peptides triggera signaling cascade, the targets of which are homeodomaincontainingtranscription factors of the WOX family that regulatethe maintenance of stem cell niches in plants . The known functions of CLE peptidesinclude control of shoot and root apical meristems and cambiumactivity,differentiation of vascular tissues, formationof lateral roots and nodules, early embryogenesis, stomataldevelopment, and response to several environmental factors:water availability and changes in soil nitrogen composition In all angiosperm species studied, the CLE peptides areencoded by numerous genes. For instance, in the relativelysmall genome of Arabidopsis thaliana, there are 32 CLE genes, and each A. thalianaCLE gene is characterized by a unique spatial patternof expression . However, some CLE genesencode the same CLE peptides. It is suggested that such an excess of CLE peptides is necessary for fine regulation ofplant development .It is obvious that the family of CLE genes is not limited bythe genes discovered to date. The accumulation of genomicdata and computer software improvement make it possibleto identify new members of this family. In our study, inthe reference potato genome, which is the sequence of thedoubled monoploid clone Solanum phureja DM-1-3 516R44, 41 CLE genes that encode 37 uniqueCLE peptides were identified. Besides, many cultivated andwild-growing potato species are known. According to variousauthors, potatoes include 112 to 235 species . The genomes of some potato species are currentlysequenced and available in genomic databases.In our work, we searched for and analyzed CLE genesin the genomes of seven potato species: three wild species and fourprimitive cultivated species . All genomes are provided inthe NCBI database. In total, we found 332 CLE genes andidentified unique peptides in individual potato species thatcan perform other unknown functions or be completely nonfunctional.In addition, we found similarities in the sequencesof different CLEs, which may indicate their common geneticorigin.We used the genome assemblies of various potato speciespresented in the NCBI database: wild species S. commersonii,S. verrucosum, and S. bukasovii, along with primitivecultivated species S. chaucha, S. juzepczukii, S. curtilobum,and S. ajanhuiri. In the present work the system of J. Hawkeswas used.Solanum commersonii is a widespread diploid potatospecies in South America, present at the coastal zone of theAtlantic Ocean, mainly located in Argentina and Uruguay. Itsnatural habitat extends from sea level to an altitude of 1300 m.S. commersonii is ruderal, and its primary habitats are rockyareas, dunes, and growing areas of cultivated plants .Solanum verrucosum is a diploid potato, which, unlike otherspecies studied in this work, is widespread in North America,more precisely in Mexico. Yet, it is believed that S. verrucosumis evolutionarily closer to the ancestors of cultivated potatospecies than S. commersonii . The habitats ofthis species are woodlandsSolanum bukasovii is a diploid South American potato speciesthat grows at an altitude of 3300\u20134000 m above sea levelin Peru. It belongs to the group of wild potato species fromwhich cultivated potato species are believed to have evolved.Solanum juzepczukii and S. curtilobum are alpine triploidand pentaploid potato species, respectively, that grow in a verylimited area. They belong to the group of \u201cbitter\u201d potatoesdue to the high content of glycoalkaloids. Only some of theirclones were found to be cultivated in the highlands of Peruand Bolivia, where other types of potatoes cannot be growndue to the conditions. They are more resistant to frost than anyother domestic potato species .Solanum ajanhuiri is a diploid alpine species. It is cultivatedat an altitude of more than 3900 m in the area of LakeTiticaca. S. ajanhuiri is also hardy, but unlike S. juzepczukiiand S. curtilobum, it has a significantly lower glycoalkaloidscontent in tubers .Solanum chaucha is a triploid species found mainly in thenorthern mountainous regions of South America and northern Peru. It is cultivated at lower altitudesthan the above-mentioned cultivated potato species.The search for CLE genes in different potato species wascarried out according to homology with genes from theCLE family in S. phureja , A. thaliana, and tomatoSolanum lycopersicum using the Nucleotide Basic Local Alignment SearchTool (BLASTN) and the discontiguous megablast algorithm in the NCBI database (https://blast.ncbi.nlm.nih.gov/Blast.cgi), where genome assemblies of all thestudied potato species are available (see the Table). The alignmentof amino acid and nucleotide sequences was carried outusing the Muscle algorithm in the MEGA7 program (https://www.megasoftware.net/) .Phylogenetic analysis was performed in the MEGA7 programusing the \u201cnearest neighbour\u201d method with default settings and a bootstrap of 1000 . CLE protein signaling domains were predictedin the SignalP-5.0 program . Consensus sequences of CLE proteins were visualizedin the Geneious Prime software (https://www.geneious.com/features/).Using the NCBI database, we identified CLE genes in sevenpotato species by homology with the CLE genes of potatoS. phureja (SphCLE), arabidopsis , and tomato(S. lycopersicum). Species being studied were primitivedomestic species S. chaucha, S. curtilobum, S. juzepczukii,S. ajanhuiri, and wild species S. bukasovii, S. commersonii,S. verrucosum 1. We also identified CLE genes in the primitive cultivated potato S. stenotomumand in the wild species S. pinnatisectum. However, due to theinsufficient quality of the genome assemblies these genes werenot selected for further analysisFor each potato species, a different number of CLE geneswas found, 40 to 43 (see the Table). This is primarily due tothe different qualities of genome assemblies. For instance, thegenome of S. verrucosum is published in the form of extendedscaffolds, while the assembly of the S. curtilobum genome ispresented at the contig level. As a result, some S. curtilobumCLEs were not included in the analysis due to contig breaksand the inability to analyze the entire gene sequence. Homologuesof most previously identified CLE genes in S. phureja(SphCLE) were found in all potatospecies analyzed. Furthermore, the gene that we named CLE42was not found in the S. phureja genome, although it is presentin all other potato species studied.Analyzing the amino acid sequences (AAS) of individualCLE proteins in different potato species, we found a highpercentage of their similarity .Moreover, there are both completely identical AAS of proteins and variants with no identical AASsamong the species . However, theCLE proteins in the studied potato species are very similar toeach other. Based on the complete protein sequence, individualCLEs form groups, each of which includes all homologues ofone CLE protein from different potato species . Amongall analyzed potato species, the CLE proteins of S. commersoniicontain a large number of unique AAs, which are absentin other species.CLE proteins include three domains: the signaling domain(SD), the variable domain (VD), and the CLE domain.The CLE domain is the most conserved functional part of the protein, and substitutions are rare here. In other proteindomains, substitutions occur much more frequently. Althoughsubstitutions in the CLE domain will bring the greatest effecton the phenotype, SD and VD are also important and are involvedin the implementation of CLE peptide function. SD andVD are active in the processing of CLE peptides and can thusinfluence the availability of mature peptides in certain cellsand tissues . It turned out that, in differentpotato species, AASs of CLE domains are almost identicalwithin each group. At the other extreme, the nucleotide sequences(NSs) of CLE domain in proteins of the same groupvary between species. For example, proteins of the CLE12group, although they have identical AASs of the CLE domains,differ in the NSs of the corresponding gene regions.Although we identified 41 CLE genes in S. phureja, theyencode 37 CLE peptides . This isbecause the AASs of CLE domains are identical in someproteins . However, inother potato species, 20 additional CLE domains were found,which are absent in S. phureja. All these domains are similarto the CLE domains of S. phureja proteins, but differ fromthem by 1\u20134 AA . As mentioned above, in some CLE proteins of the sameplant species, CLE domains are identical . In potato, 10 pairsof such proteins with identical CLE domains were found.Mature peptides that have identical AASs of CLE domains arepeptides from CLE10 and CLE38 groups, CLE17 and CLE18,CLE25 and CLE34, CLE6 and CLE19, CLE8 and CLE12.However, the remaining AASs of these proteins (outside theCLE domain) vary significantly within each pair.At the same time, some potato CLE proteins have a similarAAS, but their CLE domains are not identical and differ byone or several AAs . Interestingly, some proteins are grouped differentlydepending on whether the CLE domain or the rest ofAAS of the protein is being compared. For instance, CLE37 iscloser to CLE31 (they differ by 1 AA) when comparing their CLE domains. However, the rest of the CLE37 protein forms a group with CLE22protein. The same thing happens in the case of CLE25 and CLE34 proteins. Theseproteins have identical CLE domains, but their sequences outside the CLE domainare different and, comparing them, CLE34 is grouped with CLE36, not CLE25.Sometimes such a scenario occurs only within one potato species. For example,the CLE domain of ScoCLE4 differs by only 1 AA from CLE25 (while in otherpotato species CLE domains of CLE4 differ by 2 AA from CLE25); notably, proteinsequence outside the CLE domain belongs to CLE4. Obviously, differences in thesequence of the CLE domain shouldlead to the functional diversity of CLE proteins, despite the great similarity oftheir AASs. CLE proteins, similar in AASs, but distinct in the CLE domain, arealso found in other plant species . Their genes may have emerged as a result of duplicationswith subsequent mutations in the sequence of the CLE domain, which led tothe emergence of new functions .Indeed, some CLE genes in potatoes are duplicated, and their sequences weaklyvary from each other. For instance, in all analyzed potato species, CLE26 andCLE2 genes are duplicated. Sometimes such duplicated genes have substitutionsin CLE domain sequence, which leads to the emergence of a unique peptide . However, due to the high level of similarity, such genes arenot counted in the Table.Sometimes, CLE domains of some CLE proteins are identical in several potatospecies and differ from CLE domains of the same proteins in other species. Forexample, in the CLE26 proteins of S. juzepczukii and S. chaucha, I is in the secondposition of the CLE domain, while in other species there is L. The CLE11 proteinsof S. verrucosum, S. curtilobum, and S. juzepczukii, in the fifth position of CLE domainhave E, while in other species there is Q . The largest number ofunique CLE domains, which differ from all other potato species studied, was foundin S. verrucosum, S. commersonii, and S. juzepczukii.Great interspecies differences in the AASs of CLE proteins relate to sequencesoutside the CLE domain. Thus, among the genes of the CLE8 group, SvCLE8 standsout, which has three additional nucleotides in the VD; it makes the protein 1 AAlonger. CLE18 proteins of S. verrucosum, S. commersonii, S. bukasovii, S. chaucha,and S. juzepczukii have a region 5 AA in the VD, while CLE18 of other speciesdoes not have such a region. At the same time, S. bukasovii and S. chaucha eachhave two CLE18 genes encoding proteins with and without this region .Asimilar situation occurs for the CLE5 protein: a region 4AA in theVD is presentin S. phureja, S. curtilobum, S. juzepczukii, S. bukasovii, but absent in S. chaucha,S. verrucosum, S. ajanhuiri, S. commersonii, whereas S. bukasovii and S. juzepczukii each have two CLE5 genes encoding proteins without thisregion and with it . Sometimes, great differencesin the AASs of CLE proteins are observed only within onespecies. For example, protein SvCLE30, in contrast to CLE30of other potato species, lacks 3 AAs in the VD. In the VDof ScoCLE20, there is no fragment of 8 AAs, and its SD islengthened by 1 AA. S. juzepczukii has two CLE12 genes,and one of them encodes a protein that differs from CLE12 ofother species in that the onset of its SD is extended by 6 AAs,while 3 AAs are absent in the VD.In sum, the analysis of CLEs nucleotide and amino acidsequences of the potato species studied revealed severalexamples of polymorphism in different regions of CLE carryingdifferent functional loads. This polymorphism canaffect the activity of CLE peptides. The differences relateto CLE domain itself, from which the actual CLE peptideis formed, or to sequences outside it, which can affect theprocessing of CLE protein. At the same time, accurate dataon the functional difference between CLE proteins in potatospecies can be obtained only with a precise analysis of theirfunctions. For example, in overexpression experiments of thecorresponding genes or plant treatment with synthetic CLEpeptides of different potato species. Our research can serve asthe groundwork for further research in this area.In this research, we performed a search and analysis of thegenes encoding CLE proteins in different species of potatoes:wild and primitive cultivated. Of the 332 identified CLE genes,we found 57 genes that encode unique CLE peptides. In total,we identified 42 genes that are present in almost all potatospecies analyzed. At the same time, there are genes that arevery similar to each other in different species and those thathave significant interspecific differences. Thus, in CLE genesof S. commersonii, presumably, the largest number of uniquesubstitutions occurred, which led to serious differences in itsCLE peptides compared with those in other potato species.S. commersonii is a wild potato that differs from the rest of thespecies analyzed by its habitat. It grows outside the growingareas of cultivated potatoes and, most likely, is not among theancestors of cultivated potatoes .Some of the revealed differences in the sequences of CLEproteins are unique for a certain species of potato, while otherdifferences relate to several ones. Of special interest are theproteins CLE5 and CLE18, which vary in the presence orabsence of a region of 4\u20135 AA. At the same time, there arepotato species in which both protein variants are present , which may be associated with the natural hybridizationof potatoes .Additionally, in some potato species, substitutions occurredin CLE domain, which could affect the functionsof the corresponding peptides. For example, divergence in1 AA in CLE domain of A. thaliana CLE peptides results inthe divergence of their functions: one peptide is involved inthe response to water shortage (CLE25), while the other isnot (CLE26) . Unique peptides thatappear in individual potato species due to the differences inCLE domain can perform distinct functions or completely losefunctionality. Furthermore, changes in the sequence outside the CLE domain can also affect the functioning of the CLEpeptide and, in different potato species, changes in VD or SDmay affect peptide activity. At the same time, the sequencesimilarity of different CLEs may point to their common origin.The presence of duplicated genes, such as CLE2-2, in whichsubstitutions occur in CLE domain sequence and which maysubsequently lead to the emergence of new genes confirmsthis hypothesis.In summary, we found that CLE proteins in various potatospecies are similar; however, they also have differences thatcould affect their functioning. Further study of CLE proteinswill reveal their role in potato development.The authors declare no conflict of interest.Altschul S.F., Gish W., Miller W., Myers E.W., Lipman D.J. Basic localalignment search tool. J. Mol. 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DOI 10.1186/1471-2164-15-827."} +{"text": "Blood Cancer Journal 10.1038/s41408-018-0119-y, published online 22 August 2018Correction to: It came to the author\u2019s attention that the conflict of interest statement is incomplete, the revised COI statement is as follows:Conflict of interestH.O. and T.H. declare that they have no conflict of interest. K.C.A. serves on advisory boards for Celgene, Millennium, and Gilead Sciences, and is a scientific founder with financial interest in Acetylon, OncoPep, and C4 Therapeutics."} +{"text": "Plagiothecium in Eurasia is presented for the first time based on a thorough review of the literature. Data have been compiled from previous relevant works conducted on the genus over more than 70 years and published up to the end of June 2020 for 107 Eurasian countries (and islands). Sectional classification is based on molecular phylogeny of the genus published recently. A total of 41 taxa are reported, including 29 species and 12 infraspecific taxa (nine varieties and three forms) belonging to eight sections. The highest numbers of taxa were found in China (20 taxa), the Russian Federation (20 taxa) and Japan (18 taxa), while the smallest numbers of taxa were recorded in the Middle East, Central Asia and the islands area. Not a single species of Plagiothecium was recorded in 26 regions, whereas P. denticulatum, P. nemorale and P. cavifolium turned out to be the most widespread species in the entire study area. They were recorded in most of the surveyed countries and islands. For each accepted taxon, information on relevant literature, synonyms, distribution within Eurasia and globally are provided. Comments on each taxon, ecological preferences, and notes on doubtful records are also included. Additionally, distribution maps for each recognised taxon are supplied. This checklist can enlighten and foster a better understanding of the distribution, diversity, and ecology of Plagiothecium in Eurasia and provides an incentive for future research on the genus.An annotated checklist of the pleurocarpous moss genus Plagiothecium Schimp. (Plagiotheciaceae M. Fleisch.) was erected by Schimper and initially described in \u201cBryologia Europaea\u201d [Herzogiella Broth., Isopterygiella Ignatov & Ignatova, Isopterygiopsis Z. Iwats., Isopterygium Mitt., Pseudotaxiphyllum Z. Iwats. and Taxiphyllum M. Fleisch. Our understanding of the family Plagiotheciaceae has also changed. It has been treated for a long time as monogeneric, with the single genus Plagiothecium [The pleurocarpous moss genus uropaea\u201d to incluothecium ,3,4, butothecium ,6,7 chanPlagiothecium is a cosmopolitan genus represented in all continents, though varies in diversity and abundance, with largest concentrations in temperate, upland habitats of the Northern Hemisphere. Apart from Asia and Europe [Africa: Sub-Saharan Africa [Antarctica: [Subantarctica: [Australasia: [Australia: a single record according to Klazenga [North America: [North America North of Mexico: [South America: Tropical Andean countries [Latin America [Biogeographically, d Europe ,9 , epixylic (on wood), epigeic (on soil) or epiphytic , see, Ecologically, So far many new taxa have been globally described within the genus; however, the total number of accepted species is still uncertain . EstimatPlagiothecium given for Asia and Europe remained unchanged. For each of these continents, it remained at a similar, fairly low level, containing from a few to over a dozen species [Since the mid-twentieth century, the number of species of the genus species ,31,32,33 species ,19,29,30 species ,23,26,27Plagiothecium is usually described as very variable; however, the reasons for this variability were not analysed [The genus analysed ,29,30,34analysed ,35,36,37Plagiothecium focused mainly on the taxonomy of individual taxa or of the whole genus [Currently, research on the genus le genus ,23,26,27le genus ,40,41,42Plagiothecium taxa has never been the subject of specific studies and the fact that in recent years the taxonomic status of many species has changed. The purpose of this article is to create a checklist for Plagiothecium in Eurasia and to describe the distribution of the Eurasian taxa of this genus. To attain this goal, it was decided to amass and systematise the available knowledge in relevant literature in order to (1) identify the names of all taxa known to occur in each country (island), (2) clarify the status of names and taxa which are accepted, (3) analyse the geographic distribution, and (4) estimate species richness of Plagiothecium in Eurasia. This study is not intended to be a taxonomic revision of Plagiothecium, however it provides the latest status for all recognised taxa with their geographical distribution.The present study was carried out due to the fact that the distribution of Plagiothecium distribution and species diversity in Eurasia (and other continents as well) is still somewhat biased toward some countries while contains gaps in others due to complete lack of data or of reliable data or insufficient sampling. Not to mention the currently accelerating rate of changes in taxonomic status of many taxa as a consequence of molecular studies. The present checklist can serve as a new starting point for further research on the genus in these countries, which will likely result in addition of new records or perhaps new taxa.We tried our utmost to compile all of the relevant information to approach the purpose for this study. However, the current knowledge of The authors inviting comments and would appreciate notifications of additions and corrections to update the present checklist. Please address relevant information to the corresponding author.The present checklist includes 41 taxa, comprising 29 species, nine varieties and three forms belonging to eight sections. For two countries , no study confirming or excluding any species from the genus described could be found. The rest of Eurasia is quite well explored and widely described in terms of mosses .Plagiothecium is quite widely, but unevenly distributed : in China (20 taxa), the Russian Federation (20), Japan (18); Austria, Germany, Sweden (16), Czech Republic and Switzerland (15 taxa each) .P. argentatum, P. cochleatum, P. conostegium, P. decoratum, P. subglaucum) was reported both in Asia and Europe , P. nemorale , and P. cavifolium , they were considered as common in the study area were reported only from one to five countries, and in the Eurasia they were recognised to be very rare. Wherein, 12 of them were lisd Europe . The freudy area .Plagiothecium taxa include brief description for each taxon, with comments on nomenclature and taxonomic status (when necessary), ecological preferences, and geographic distribution inside and outside Eurasia (if available).Annotations to the following list of Taxon distribution per country in Eurasia is given in detail in We did not make any broad attempt to provide an exhaustive list of records for all countries in each continent (outside Eurasia), but we gave a general overview of the geographic distribution outside the study area based on the selected references. As far as we know, none of the 41 taxa listed here have been reported from Antarctica or AustrPlagiothecium angusticellum G.J. Wolski & P. Nowicka-Krawczyk 2020\u2014a medium-sized plant, with asymmetrical leaves, not shrunken when dry; an acuminate, gently curved, not serrated apex; tight areolation, created with long and narrow leaf cells which do not form regular rows. This combination of features made it possible to distinguish P. angusticellum from similar and closely related species such as P. cavifolium, P. nemorale, and P. longisetum [Ecology. From Poland (from where it was described), this species was recorded mainly in deciduous forests 1987, wet alder riparian forests Fraxino-Alnetum W. Mat. 1952, beech forests Luzulo pilosae-Fagetum W. Mat. et A. Mat. 1973, oaklinden-hornbeam forests Tilio-Carpinetum Tracz. 1962) in epigeic, epiphytic and epilithic habitats. Distribution. Apart from Central Europe, this species is also reported from North America (USA) [ngisetum . Ecologyca (USA) .Plagiothecium argentatum (Mitt.) Q. Zuo 2011\u2014described as Hypnum argentatum by Mitten [Struckia by M\u00fcller [Plagiothecium [Plagiothecium) set of features. Most of these features place P. argentatum well in the described genus, but serrulate margins, absence of decurrency and quadrate alars seem to exclude this species from the genus Plagiothecium. This large morphological separateness resulted in the placement of this species (as P. enerve) in a separate section of Struckia [Ecology. The species was recorded in epiphytic and epixylic habitats [Distribution. So far, recorded from East and South Asia.y Mitten , transfey M\u00fcller , and finothecium , its intothecium ,23). A phabitats . DistribPlagiothecium berggrenianum Frisvoll 1981\u2014a medium-sized to large, julaceous, crowded plant; leaves symmetrical, very concave, ovate, long decurrent, and an abruptly narrowed to hooked apex; leaf cells long and narrow, thick-walled; capsules straight and erect. This circumpolar species was described by Frisvoll [Plagiothecium berggrenianum is similar to P. svalbardense, but the former is longer, with elliptical, plicate leaves, and broadly recurved margins. Wynns [P. berggrenianum is a possible hybrid. Ecology. This species is recorded in epigeic, epilithic and epixylic habitats [Distribution. Apart from Eurasia, it is also reported from North America [Frisvoll , and is s. Wynns states thabitats ,171,172.habitats . Distribnd, USA) ,172.Plagiothecium cavifolium (Brid.) Z. Iwats. 1970\u2014Iwatsuki [P. roeseanum [Ecology. This species is found in shaded locations in low to high elevations [Distribution. Apart from Eurasia, this species is also reported from Africa (Tunisia) [Iwatsuki selectedevations and recoevations ,199). DiTunisia) ; North ATunisia) ,23,25,79Plagiothecium cavifolium var. orthocladium (Schimp.) Z. Iwats. 1970\u2014Iwatsuki [P. orthocladium [P. nemorale fo. japonicum (currently P. japonicum) as well as P. succulentum. Wynns [Ecology. This taxon is recorded in epilithic habitat. Distribution. Apart from Europe (Nordic countries), this taxon is also reported from North America [Iwatsuki selectedPlagiothecium cochleatum Dixon 1938\u2014a dark green plant; leaves loosely imbricated, concave, plicate, with rigid areolation, and quite well-developed alar decurrencies. Wynns [P. cochleatum is similar to P. cavifolium and may be confused with this species. Ecology. It is a rare species, present in disjunct Alpine and Himalayan habitats [Distribution. So far, it is reported from Asia (India).s. Wynns indicatehabitats . DistribPlagiothecium conostegium Herzog 1916\u2014Suzuki [P. longisetum. This requires checking herbarium materials, but at this stage, we consider the presence of P. conostegium doubtful in Eurasia. Ecology. In Central and South America, it is recorded as a forest species mostly growing on epigeic, epilithic, epiphytic and epixylic habitats [Distribution. Apart from Asia (Japan) [6\u2014Suzuki recorded6\u2014Suzuki in parti6\u2014Suzuki looks mohabitats ,7. Distr (Japan) , the spe (Japan) .Plagiothecium curvifolium Schlieph. ex Limpr. 1897\u2014a small to medium-sized plant, green to yellowish green, glossy (P. laetum). Ireland [P. curvifolium and P. laetum as separate species, but DNA analysis clearly proves this [Ecology. It is recorded in epigeic, epilithic, epixylic and epiphytic habitats ,200Plagind areas . Outsidend areas but its nd areas . It is and areas ,79.Plagiothecium curvifolium fo. julaceum Culm. & E. Bauer 1915\u2014it is a forgotten taxon, which after being described in 1915 it was not later mentioned as a separate or at least as a synonym in any of the major bryological studies [ramis subjulaceis, foliis imbricatis saepe subhomomallis) indicates features similar to P. cavifolium. At this stage, this taxon definitely requires further in-depth research and detailed analysis. Ecology and Distribution. Detailed ecological data and distribution for this taxon are not known exactly and require specific investigation. However, according to Wynns [ studies ,204,205. studies recognisto Wynns , the isoPlagiothecium decoratum J.T. Wynns 2015\u2014the species established by Wynns [Ecology. It is listed in epiphytic habitat [Distribution. The species is described as endemic of Bhutan and Nepal [by Wynns and desc habitat . Distribnd Nepal , presentnd Nepal , this taPlagiothecium denticulatum (Hedw.) Schimp 1851\u2014a fairly large plant, green to yellowish green, often glossy ,206Plagis et al. ; also ths et al. . It is as et al. ,79,207.Plagiothecium denticulatum var. affine Warnst. 1906\u2014a species with small, flat, asymmetric leaves and well-developed alar regions [P. denticulatum var. affine has a delicate form and resembles P. laetum, and that it could be an intermediate form between these species. Intermediate features of this taxon include its delicate structure as well as straight and erect capsules . Wynns [Ecology. Warnstorf [Distribution. So far, it is reported only from Germany [ regions . Warnsto regions stated t). Wynns supportsarnstorf did not igsberg) ,208.Plagiothecium denticulatum var. obtusifolium (Turner) Moore 1873\u2014a small, subjulaceous, glossy, soft plant; leaves round, ovate or elliptical, with an obtuse apex, recurved margins and well-developed alar regions. These features distinguish this taxon from other species. Plagiothecium denticulatum var. obtusifolium was treated by some scientists as a synonym of P. denticulatum [m or consme taxon . Ecologyda, USA) .Plagiothecium enerve (Broth.) Q. Zuo 2011\u2014due to a rather unusual combination of features: small plant with not tumid branches, narrowly lanceolate leaves bordered by hyaline, elongate, thin-walled cells, with an extremely long, often brownish piliferous apex, this plant was first described as Struckia enervis [Plagiothecium. Ecology. This species is recorded in epilithic and epiphytic habitats [Distribution. Until now, it is reported from Asia (China and Russia). enervis . However enervis indicatehabitats . DistribPlagiothecium euryphyllum (Cardot & Th\u00e9r.) Z. Iwats. 1970\u2014a medium-sized to robust, glossy plant, with flattened branches; leaves ovate to elliptical, asymmetric, slightly contorted when dry, broadly acute, more or less undulate; median leaf cell linear, narrow, thin-walled, areolation looks tight. Due to this feature combination, P. euryphyllum is similar and confused with P. neckeroideum, but this species does not have intense iridescent and concave leaves as P. euryphyllum. Ecology. The species is recorded in epigeic, epilithic, epixylic and epiphytic habitats [Distribution. It is widely spread over Asia and Eastern Europe (Russia) [habitats ,64,79. D(Russia) ,72,140.Plagiothecium fallax Cardot & Th\u00e9r. 1902\u2014Cardot & Th\u00e9riot [P. fallax is similar to P. denticulatum sensu lato, but it can be distinguished from this species by very small alar decurrencies. Ireland [P. cavifolium. Ecology. This species is recorded in epigeic habitat. Distribution. Apart from Eurasia (Russian Federation and Japan), it is also reported from North America (USA) and considered to be a typical North Pacific element [ Th\u00e9riot describe Ireland and Iwat Ireland treated element .Plagiothecium japonicum Sakurai 1949\u2014described by Sakurai [P. nemorale , later even as a synonym to this species [Plagiothecium japonicum can be easily recognised by large, broadly ovate, often concave leaves with stiff, extended cells and, as indicated by Wynns [P. nemorale and P. cavifolium. Ecology. This species is recorded in epigeic and epilithic habitats. Distribution. Apart from Asia (Japan), it is also reported from North America (USA) and considered a North Pacific element as P. fallax [ Sakurai , but Iwa Sakurai treated species . Plagiotby Wynns , it shou. fallax .Plagiothecium laetum Schimp. 1851\u2014small plant, pale green to yellowish green, glossy, in loose mats; leaves asymmetrical, narrowly ovate-lanceolate, and narrowly-decurrent, gradually acuminate at apex; median leaf cells linear-rhomboidal; capsules more or less erect. Narrow alar decurrencies and sporophytes with erect capsules easily distinguish this species from closely related ones such as P. curvifolium. A recent taxonomic study of P. laetum complex allowed description of a new species, i.e., P. rossicum [Ecology. The species recorded in epigeic, epilithic, epixylic, and epiphytic habitats [rossicum . Ecologys e.g., ,195,212),212Plagind, USA) ,18,79.Plagiothecium laetum var. tenellum (Schimp.) Warnst. 1906\u2014Warnstorf [P. laetum by longer, more lanceolate leaves, as well as narrow and long cells. Jedli\u010dka [P. laetum var. tenellum as having small, narrow leaves, very short costae and narrow cells, often with propagules, and small erect capsules. Ecology and Distribution. Warnstorf [tenellum plants are from all locations listed to P. laetum, which include Germany . The ecological data reported for these locations were: very rare in pine and deciduous forests at the bottom of trees or on forest floor, sometimes also in moors on the edge of old peat holes; often in crevices of lower and higher mountains.arnstorf states tJedli\u010dka ,203 chararnstorf did not Plagiothecium latebricola Wilson ex Schimp. 1851\u2014a small, slender, bright green or yellowish green, glossy plant; leaves erect-spreading, symmetrical, narrowly ovate-lanceolate, sometimes complanate, long acuminate, at times shrunken when dry, a margin narrowly recurved, entire or denticulate near the apex; costae very short; median leaf cells linear-rhomboidal; alar regions narrowly decurrent; fusiforme gemmae often present as well as rhizoids at the apex; capsules erect. Because of its small size, colour, short costae, narrow decurrent alar regions and erect capsules, this species can be confused with P. laetum, but even leaf symmetry in the latter helps to distinguish these two species. Ecology. Plagiothecium latebricola is found in swamps, fens, marshes and recorded in epigeic, epilithic, epixylic and epiphytic habitats ,213Plagiribution , typicalribution . Apart fribution .Plagiothecium longisetum Lindb. 1872\u2014species described by Lindberg [P. nemorale by Iwatsuki [P. nemorale and other closely related species. Ecology. It is recorded in epigeic, epilithic, epixylic and epiphytic habitats [Distribution. Apart from Eurasia, this species is also reported from North America [Lindberg , synonymIwatsuki and treaIwatsuki , recentlIwatsuki . A robushabitats . Distribda, USA) .Plagiothecium neckeroideum Schimp. 1851\u2014a robust, green to yellowish green, strongly complanate plant; leaves domorphic, triangular, asymmetrical, ovate, undulate, concave, and a serrulate apex; median leaf cells linear-rhomboidal, narrow; alar decurrencies hyaline, thin-walled and well-developed. Apex cells are nematogenous, leaves often with differentiated apical cells, often seen as a longitudinal brown stripe at the leaf apex. Ecology. It is noted in epigeic, epilithic, epixylic and epiphytic habitats . Deng-ke and Ireland [s [Distribution. So far, the taxon is known only from Nepal.by Wynns as a smaiphytic) . DistribPlagiothecium neckeroideum var. javense M. Fleisch. 1920\u2014Fleischer [Ecology. This taxon was recorded in epigeic and epilithic habitats. Distribution. Apart from Southeast Asia , it is also reported from Papua New Guinea [leischer describew Guinea and fromw Guinea .Plagiothecium neckeroideum var. myurum Molendo 1875\u2014smaller than P. neckeroideum var. javense, other features that make it different from closely related species are that it is a julaceous plant, with strongly concave, not undulate leaves [Ecology. It is a montane taxon, recorded in epigeic, epilithic, epixylic and epiphytic habitats [Distribution. Reported from Sino-Himalayan region [e leaves . Ecology, Nepal) .Plagiothecium neckeroideum var. niitakayamae (Toyama) Z. Iwats. 1970\u2014a big, light green, julaceous plant, with symmetrical, plicate leaves; this variety differs from the species by more julaceous, symmetric, undulate leaves. Ecology. This taxon was recorded in epigeic, epilithic and epiphytic habitats [Distribution. Recorded from East Asia and Southeast Asia (Philippines).habitats ,79. DistPlagiothecium neckeroideum fo. parvum J.T. Wynns 2015\u2014a form proposed by Wynns [P. subglaucum, but in P. neckeroideum fo. parvum the leaves are broader. Ecology. This taxon was recorded in epigeic habitats [Distribution. So far, it is known only from Taiwan (East Asia).by Wynns , who deshabitats . DistribPlagiothecium nemorale (Mitt.) A. Jaeger 1878\u2014this species has been too widely described in the last few decades, a taxonomic review of P. nemorale sensu lato indicates that it is actually three separate species: P. nemorale sensu stricto, P. longisetum and P. angusticellum [Ecology. The species is recorded in epigeic, epilithic, epixylic, and epiphytic habitats ,218Plagi Eurasia . It is a Eurasia ,47 from Eurasia ,191.Plagiothecium noricum Molendo ex Limpr. 1897\u2014flaccid, not undulate, very concave leaves, with expended cell aerolation, denticulate; rhizoids at the apex. Ecology. Wynns [P. noricum as a still little-known Alpine species, where are listed from epigeic habitat. Distribution. Reported from the Southern part of Central Europe (Austria) and Southeast Asia (Myanmar).Plagiothecium obtusissimum Broth. 1921\u2014a yellowish green to pale green, glossy plant with metallic luster; leaves ovate, rounded-obtuse at the apex, asymmetrical, slightly concave, the margin often erect at one side; leaves with suddenly differentiated alars, composed by hyaline inflated cells; median cells linear-flexuose, very narrow and long, thin-walled. Iwatsuki [P. obtusissimum to be closely related to P. euryphyllum, due to similar alar cells, leaf cells and setae. Additionally, it is easily distinguished from this species by the plant size and shape of leaf apex. DNA analysis confirms the observations about the close relationship between these species [Ecology. Plagiothecium obtusissimum is recorded in epigeic, epilithic, epixylic and epiphytic habitats . Dis. DisPlag Noguchi ).Plagiothecium piliferum (Sw.) Schimp. 1851\u2014a small, slender, pale green and glossy plant; leaves ovate, deeply concave, almost symmetrical, abruptly contracted to a piliferous, sometimes flexuose apex, with recurved margins; median leaves linear-rhomboidal, very narrow; alar regions narrowly decurrent. Ecology. Plagiothecium piliferum is recorded in epigeic, epilithic, and epixylic habitats in low to moderate elevations [s [ Ireland , it is aNA study suggestes e.g., ,128,194),194Plagida, USA) .Plagiothecium rhizophyllum Sakuri 1932\u2014described by Sakurai [P. nemorale, but Wynns [P. rhizophyllum as a separate species. Ecology. It is recorded in epigeic habitat [Distribution. So far, the species reported only from East Asia (China). Sakurai as a sma Sakurai ,221 and Sakurai ) consideut Wynns treats P habitat . DistribPlagiothecium rossicum Ignatov & Ignatova 2019\u2014described on the basis of DNA analyses of the P. laetum complex by Ignatova et al. [P. laetum, but a flat margin and strongly asymmetric leaves are very useful in distinguishing P. rossicum from this species. Many features allow this species to be distinguished also from P. svalbardense, including for example: A flat leaf margin, narrow cells, narrowly acute to short acuminate apex which characterise P. rossicum. Ecology. So far, this species has been recorded in epigeic, epilithic, epixylic and epiphytic habitats [Distribution. The species in common in boreal and hemiboreal forests of Russia, one position is also given from Poland [a et al. . A smallhabitats . Distribm Poland .Plagiothecium ruthei Limpr. 1897\u2014a medium-sized to large plant; leaves strongly complanate on the stem, transversely undulate when moist, sometimes shrunken when dry, flaccid, acuminate, strongly asymmetrical, on side almost straight, leaves with narrowly recurved margins and well-developed alar regions. These features distinguish this species from other closely related species. It is recognised as a separate species throughout Eurasia, despite the fact that DNA data places this plant closer to P. denticulatum, even closer than P. denticulatum var. obtusifolium [Ecology. Plagiothecium ruthei is typical of wetlands species, recorded in epigeic, epixylic, and epiphytic habitats .,194.Plags et al. ; and froPlagiothecium ruthei var. rupincola Limp. 1897\u2014Limpricht [P. ruthei due to the size and cell areolation, but different due to closer foliage; symmetrical leaves, lacking recurved margin. Ecology. Limpricht [Distribution. According to the protologue and Wynns [impricht describeimpricht describePlagiothecium subglaucum Thwaites & Mitt. 1873\u2014Mitten [Plagiothecium subglaucum is similar to and can be confused with P. neckeroideum. Both species require further in-depth research [Ecology. It is recorded in epigeic and epiphytic habitats. Distribution. So far, known only from Sri Lanka (South Asia) and Myanmar (Southeast Asia).3\u2014Mitten describePlagiothecium succulentum (Wilson) Lindb. 1865\u2014a robust, yellowish green to golden green, very glossy plant, leaves symmetric, lanceolate, not shrunken when dry, with an entire apex; median leaf cells very long. Plagiothecium succulentum differs from P. nemorale by lanceolate leaves, longer cells and a smooth apex; and from P. longisetum by lanceolate, symmetrical leaves; from other closely related species , it is very easy to distinguish, for example, by leaf symmetries and loose cells areolation [P. succulentum as problematic and described this species as polyphyletic or intermediate between P. nemorale and P. cavifolium. Plagiothecium succulentum in some countries is indicated as doubtful [eolation . Wynns [eolation considerdoubtful . In our s e.g., ,79,194).,194.PlagTunisia) ; and froTunisia) .Plagiothecium succulentum fo. propaguliferum E. Bauer 1902\u2014a very dark, small plant, with shrunken leaves when dry. These are the features that distinguish this form from P. succulentum. Wynns [P. succulentum. Ecology. This taxon is recorded in epilithic and epiphytic habitats [Distribution. Currently, P. succulentum fo. propaguliferum is recorded in Western, Northern and Western Europe [m. Wynns commentehabitats . Distribn Europe , and fron Europe ,191.Plagiothecium svalbardense Frisvoll 1996\u2014a small, growing erect plant, crispy when dry; leaves small, weakly undulate, concave, symmetrical to slightly asymmetrical, short, ovate, gradually tapered to the apex; margins narrowly recurved, entire or minutely denticulate at the apex; a subpiliferous apex; capsules straight and erect. Plagiothecium svalbardense is different from P. laetum by leaf shape and apex shape, the described species is also similar to P. piliferum due to its apex, but the latter has narrower leaf cells and a longer apex. The shape and arrangement of capsules is similar to P. laetum and P. berggrenianum but different from P.curvifolium. Ecology. Wynns [P. svalbardense as an arctic species, where it is recorded in epilithic and epixylic habitats [Distribution. Apart from Eurasia , this species is also reported from North America (Greenland) [y. Wynns describehabitats . Distribeenland) .Plagiothecium undulatum (Hedw.) Schimp. 1851\u2014a large white to pale green, dull plant; leaves large, imbricate, crispate, slightly asymmetric, acute and serrulate at the apex; rhizoids occur at the leaf insertion; leaf cells with papillae on abixal surfaces. These mentioned features led Ireland [P. draytonii (Sull.) E.B. Bartram) a separate genus\u2014Buckiella Ireland. Plagiothecium undulatum is similar to P. neckeroideum, but it differs by size and colour of the plant as well as longer and broader median leaf cells. Ecology. Plagiothecium undulatum was recorded in epigeic, epilithic, and epiphytic habitats [ Ireland to creats e.g., ,79,197).,197.PlagPlagiothecium had never been reported from Sinai, see [Europe ;Asia-Temperate , Western Asia, the Arabian Peninsula, China, Mongolia, and Eastern Asia); andAsia-Tropical .The present study covers Eurasia , which cnai, see ). The arnai, see , it inclA list of Eurasian countries and islands, along with their abbreviations used throughout the text, is presented in alphabetical order in Plagiothecium in all European and Asian biogeographic regions or countries. Information on species names, occurrence, distribution, ecology and taxonomy have been compiled from these publications, which covered almost all the work published on Plagiothecium over a period of more than 70 years by several authors and written in different languages. In addition, the authors\u2019 own observations and online databases/checklists available on bryophytes of several regions/countries under consideration were used. All synonyms appearing in the collected literature were compiled for each taxon , rare (6\u201310%), frequent (11\u201325%), very frequent (from 26\u201350%) and common .Plagiothecium established by Wynns [P. handelii Broth. and P. paleaceum (Mitt.) A. Jaeger, which after Wynns and Schr\u00f6ck [Ortholimnobium handelii (Broth.) C. Schr\u00f6ck & J.T. Wynns and O.paleaceum (Mitt.) C. Schr\u00f6ck & J.T. Wynns, respectively. Whereas taxa considered in this study and not included in [P. rossicum Ignatov & Ignatova, which was established by Ignatova et al. [P. laetum complex; as well as P. angusticellum G.J. Wolski & P. Nowicka-Krawczyk and P. longisetum Lindb., which were erected and resurrected, respectively, based on application of polyphasic approach to investigate the P. nemorale sensu lato [The revised sectional classification of by Wynns based on Schr\u00f6ck were sanluded in are: P. a et al. based onnsu lato .Plagiothecium sect. Leptophyllum (for P. rossicum) and Plagiothecium sect. Orthophyllum (for P. angusticellum and P. longisetum) and so this was adopted and included below (based on the literature cited in the two sections above).All species are classified into the sections proposed by Wynns and WynnAll the following sections are represented in Eurasia.Note. Included taxa listed here are as provided in [vided in ,26,27,37Plagiotheciaceae M.Fleisch., Nova Guinea 8: 748. 1912;in Engler and Prantl, Nat. Pflan-Hypnaceae subfam. Plagiothecioideae Brotherus Plagiothecium Schimper.zenfam. 1(3): 1021, 1078. 1908, \u201cPlagiothecieae\u201d. Type. Plagiothecium Schimper in Bruch, Schimper and G\u00fcmbel, Bryol. Eur. 5:179. 1851 \u2261Stereodon (Bridel) Mitten sect. Plagiothecium (Schimper) Mitten, J. Linn. Soc., Bot. 4:Plagiothecium denticulatum (Hedwig) Schimper in Bruch, Schimper and G\u00fcmbel, Bryol. Eur.88. 1859. Type. Plagiothecium Schimp. sect. Plagiothecium \u2261 Plagiothecium sect. Falciphyllum Jedl., nom. illeg. Spisy Vyd\u00e1. P\u0159\u00edr. Fak. Masarykovy Univ. 308: 23. 1948. = Plagiothecium sect. Rostriphyllum Jedl. Spisy Vyd\u00e1. P\u0159\u00edr. Fak. Masarykovy Univ. 308: 32. 1948.P. brasiliense (Hampe) A. Jaeger, P. cochleatum Dixon, P. conostegium Herzog, P. denticulatum (Hedw.) Schimp, P. lamprostachys (Hampe) A. Jaeger, P. berggrenianum Frisvoll, P. membranosulum M\u00fcll. Hal., P. nitens Dixon, P. ovalifolium Cardot, P. platyphyllum M\u00f6nk., P. ruthei Limpr., P. selaginelloides M\u00fcll. Hal.This section consists of 12 species: Plagiothecium sect. Orthophyllum Jedl. Spisy Vyd\u00e1. P\u0159\u00edr. Fak. Masarykovy Univ. 308: 35. 1948.P. angusticellum G.J. Wolski & P. Nowicka-Krawczyk, P. cavifolium (Brid.) Z. Iwats., P. japonicum Sakurai, P. longisetum Lindb., P. nemorale (Mitt.) A. Jaeger, P. rhizophyllum Sakurai, P. succulentum (Wilson) Lindb.This section consists of 7 species: Plagiothecium sect. Leptophyllum Jedl. Spisy Vyd\u00e1. P\u0159\u00edr. Fak. Masarykovy Univ. 308: 23. 1948. = Plagiothecium sect. Philoscia (Berk.) Ochyra. Biodiversity of Poland 3: 177. 2003. \u2261 Philoscia Berk. Handbook of British Mosses 49, 146. 1863.P. andinum (Hampe) A. Jaeger, P. curvifolium Schlieph. ex Limpr., P. funale J.T. Wynns, P. laetum Schimp., P. latebricola Wilson ex Schimp., P. lucidum (Hook. f. and Wilson) Paris, P. mollicaule R.S. Williams, P. pacificum J.T. Wynns, P. rhizolucidum J.T. Wynns, P. rossicum Ignatov & Ignatova, P. svalbardense Frisvoll.This section consists of 12 species: Plagiothecium sect. Pseudo-Neckera (Kindb.) J.T. Wynns. Cladistics 34: 469\u2013501. 2018. \u2261 Plagiothecium subgen. Pseudo-Neckera Kindb. European and North American Bryineae (Mosses) 1: 69. 1897.P. decoratum J.T. Wynns, P. neckeroideum Schimp., P. noricum Molendo ex Limpr., P. subglaucum Thwaites & Mitt.This section consists of 4 species: Plagiothecium sect. Lycambium Jedl. 1948. Spisy Vyd\u00e1. P\u0159\u00edr. Fak. Masarykovy Univ. 308: 10. 1948. \u2261 Buckiella Ireland. Novon 11(1): 55. 2001.P. draytonii (Sull.) E.B. Bartram, P. fallax Cardot & Th\u00e9r., P. undulatum (Hedw.) Schimp.This section consists of 3 species: Plagiothecium sect. Saviczia (Abramova & I.I. Abramov) Z. Iwats. J. Hattori Bot. Lab. 33: 341. 1970. \u2261 Saviczia Abramova & I.I. Abramov. Novosti Sist. Nizsh.Rast. 1966: 298. 1966.P. euryphyllum (Cardot & Th\u00e9r.) Z. Iwats., P. obtusissimum Broth.This section consists of 2 species: Plagiothecium sect. Struckia J.T. Wynns. Cladistics 34: 469\u2013501. 2018. \u2261 Struckia M\u00fcll. Hal. Arch. Vereins Freunde Naturgesch. Mecklenburg 47: 129. 1893.P. argentatum (Mitt.) Q. Zuo, P. enerve (Broth.) Q. Zuo.This section consists of 2 species: Plagiothecium sect. Rectithecium (Heden\u00e4s & Huttunen) J.T. Wynns. Cladistics 34: 469\u2013501. 2018. \u2261 Rectithecium Heden\u00e4s & Huttunen. Bot. J. Linn. Soc. 171(2): 344. 2013.P. piliferum (Sw.) Schimp.This section consists of one species: Plagiothecium sect. Ortholimnobium. It should be noted, however, that this section includes the two species P. handelii and P. paleaceum, which are not considered in the present study in light of the new evidence published by Wynns and Schr\u00f6ck [Note: All sections proposed by Wynns and Wynn Schr\u00f6ck , as expl"} +{"text": "Due to a production error, there was an error in the reference details for Palmiero et al., 2019.Front. Psychol. 10:1274. 10.3389/fpsyg.2019.01274,\u201d it should be \u201cPalmiero, M., Giulianella, L., Guariglia, P., Boccia, M., D'Amico, S., and Piccardi, L. (2019). The dancers' visuospatial body map explains their enhanced divergence in the production of motor forms: evidence in the early development. Front. Psychol. 10:768. 10.3389/fpsyg.2019.00768.\u201dInstead of \u201cPalmiero, M., Giulianella, L., Guariglia, P., Boccia, M., D'Amico, S., and Piccardi, L. (2019). The dancers' visuospatial body map explains their enhanced divergence in the production of motor forms: evidence in the early development. The publisher apologizes for this mistake. The original article has been updated."} +{"text": "Complement. Ther. Med. 23, 714\u2013718. doi: 10.1016/j.ctim.2015.08.002\u201d should be removed from the reference list, and the in-text citation \u201cDileo et al., 2021\u201d should instead be written as \u201cDileo et al., in preparation.\u201dDue to a production error, a reference was wrongly included in the reference list and incorporated an incorrect DOI. The reference \u201cDileo, C., Hunt, A., Vetri, R., Raffa, R. B., and Rupnow-Kidd. (2021). Effects of music therapy entrainment on pain, vital signs, and bowel function of cancer patients. The publisher apologizes for this mistake. The original article has been updated."} +{"text": "Brassica rapa) in South Africa\u2019, Journal of the South African Veterinary Association 92(0), a2106. https://doi.org/10.4102/jsava.v92i0.2106, an author name was incorrectly spelt as Mark G. Collet. The correct spelling is Mark G. Collett. The authors apologise for this error. The correction does not change the study\u2019s findings of significance or overall interpretation of the study\u2019s results or the scientific conclusions of the article in any way.In the original article published, Davis, A.J., Collet, M.G., Steyl, J.C.A. & Myburgh, J.G., 2021, \u2018Hepatogenous photosensitisation in cows grazing turnips ("} +{"text": "Nature Communications 10.1038/s41467-021-23770-0, published online 9 June 2021.Correction to: Nat. Metab. 2, 1482\u20131497 (2020). The correct form of Ref. 72 is: Gao, Z. et al. Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease. Nat. Metab. 2, 1482\u20131497 (2020). This has been corrected in the PDF and HTML versions of the Article.The original version of this Article contained an error in Ref. 72, which was incorrectly given with the wrong author names as: Mendez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease."} +{"text": "Cell Death Dis 10.1038/cddis.2013.563 published online 23 January 2014Retraction to: The Editors-in-Chief have retracted this article because concerns have been raised about the reliability of the presented data. An investigation by the US Office of Research Integrity has concluded that western blot images for total protein expression in human cell lines subject to gene depletion and/or overexpression were produced by reusing immunoblot bands and relabeling them to represent different experiments in seven figure panels in five papers and one grant application. In this article, this affects Fig. 5B, representing p53 and p63 levels in human lung epithelial cells with or without gene depletion.Authors M. Story and J. W. Shay agree to this retraction. Authors Y. Wang and W. L. Ng do not agree to this retraction. Authors A. R. M. R. Amin and F. A. Cucinotta have not responded to any correspondence from the editor or publisher about this retraction. The Publisher has not been able to obtain a current email address for authors G. Chen, M. Wang, H. Wang, X. Zhang, J. Wang and B. Hu."} +{"text": "Hemiboeachanii, a new species of Gesneriaceae from Ha Giang Province, northern Vietnam, is here described and illustrated. It has many branched stems, diamond-shaped involucre with two cirrose opposite apices, a pink corolla, red spotted inside, and a flowering time in January-February. Among congeners with an externally hairy corolla, this new species is morphologically close to H.crystallina and H.sinovietnamica. Diagnostic discriminative characters in all mentioned species are discussed. The conservation status of this species is considered to be \u201cCritically endangered\u201d (CR) according to the IUCN Red List Categories and Criteria. HemiboeaGesneriaceae) contained about 23 species and 5 varieties, distributed mainly from northern Vietnam to southern and eastern China to southern Japan J.Huang, X.G.Xiang & Q.Zhang in H.subcapitatavar.guangdongensis (Z.Y.Li) Z.Y.Li became H.guangdongensis (Z.Y.Li) X.Q.Li & X.G.Xiang in Hemiboea comprises at least 39 species and 5 varieties.Prior to 2011, rn Japan . In 2011Hemiboea . During Hemiboea and one Hemiboea a. In adds Z.Y.Li was acceHemiboea. The genus characteristics are calyx 5-parted to the base, stamens 2, staminodes 3, stigma 1 (undivided), and capsule oblique in relation to pedicel, narrowly lanceolate, somewhat curved, dehiscing adaxially; valves 2, straight, not twisted. After consulting relevant literature of Hemiboea . The photographs used for the species illustration were taken in the species natural habitats. Morphological observations and measurements were made on living plants, dry specimens, and materials preserved in alcohol. Morphological characters are described using the terminology proposed by Taxon classificationPlantaeLamialesGesneriaceaeC.H.Nguyen & Aver.sp. nov.893F573D-D125-5EDB-98B7-D722A2684F79urn:lsid:ipni.org:names:77221221-123\u00b000'14.9\"N 104\u00b054'55.9\"E, altitude 533 m, 19 January 2021, N.V.Ly, NVL 20210119001 .Vietnam. Ha Giang Province: Vi Xuyen District, Minh Tan Village, primary evergreen broad-leaved forest, around point Hemiboeachanii is similar to H.crystallina Y.M.Shui & W.H.Chen in the shape of leaf blade, leaf margin and the externally pubescent corolla, but differs in having non-inflated nodes, diamond-shaped not winged involucre, flat calyx margin, corolla red-spotted inside with a ring of hairs, and stigma slightly swollen. It also morphologically resembles H.sinovietnamica W.B.Xu & X.Y.Zhuang but differs in having 4\u20138 branches on main stem, repand-crenate leaf margin, involucre diamond-shaped with a cirrose apex, and pink corolla and a slightly swollen stigma Chew, Primulinabalansae (Drake) Mich.M\u00f6ller & A.Weber, and Rhaphidophoradecursiva (Roxb.) SchottThe new species is only known from Minh Tan Village, Ha Giang Province, growing in cracks of limestone rocks in moist shady places or occasionally in the upper part of slopes, and on rocky hilltops in primary evergreen broad-leaved forests on karstic limestone at elevations 500\u2013700 m a.s.l. Some of main herbaceous species accompanying the new species have been recorded as Flowering from January to February, and fruiting from February to April.Hemiboeachanii is named in honor of the lecturer, Mr. Le Mong Chan, for his outstanding contributions to the conservation of the flora of Vietnam.2. The population and habitat are greatly susceptible to various human activities and damage, particularly forest logging, agriculture, and grazing. There is a high risk of habitat degradation in the future because it is located close to the local village. Following the IUCN Red List Categories and Criteria , non inflated nodes (vs. nodes inflated), 1-veined calyx with flat, not revolute margin , corolla red spotted inside with a ring of hairs , and stigma slightly swollen (vs. stigma not swollen). The new species differs from H.sinovietnamica in having a subterete, 4\u20138 branched stem up to 90 cm tall , repand-crenate leaf margin (vs. entire leaf margin), involucre diamond-shaped with a cirrose apex (vs. involucre triangular with acute apex), corolla pink (vs. corolla yellowish), stigma slightly swollen (vs. stigma distinctly capitate), and a flowering period lasting in January-February (vs. flowering period lasting during August-October). The comparison of the key morphological characters of H.chanii, H.crystallina, and H.sinovietnamica is presented in Table"} +{"text": "Epimedium jinchengshanense Y. J. Zhang & J. Q. Li 2014 is an important ornamental and medicinal herb, but of unclear taxonomy. In this study, the complete chloroplast genome of E. jinchengshanense was sequenced. The genome was 157,169\u2009bp in length, with a large single-copy region of 88, 520\u2009bp, a small single-copy region of 17,075\u2009bp and 2 inverted repeat regions of 25, 787\u2009bp. The genome consisted of 113 unique genes, including 79 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The GC contents were 38.78%. Phylogenetic analysis showed a close relationship between E. jinchengshanense and E. ilicifolium, which was explained by the morphological similarity of flowers and leaves of the two species. A specimen was deposited at the Herbaria of Jiangxi University of Chinese Medicine under the voucher number S. X. Liu & L. J. Liu 2016027. DNA was isolated from 0.3\u2009g silica-dried leaf tissue using the CTAB protocol (Doyle and Doyle E. ilicifolium (NC_044897) as a reference. The software Geneious primer (www.geneious.com) was used for further manual annotation with E. ilicifolium as a reference. The cp genome sequence of E. jinchengshanense was deposited in the GenBank database (MZ603799).The sample of Epimedium was reconstructed based on cp genomes of E. jinchengshanense and additional 14 Epimedium species previously reported, with Vancouveria hexandra (MH423073) as an out-group. Using PhyML v.3.0 region of 88,520\u2009bp, a small single-copy (SSC) region of 17,075\u2009bp and 2 inverted repeat regions (IRs) of 25,787\u2009bp. The overall GC content was 37.78%, with 37.37%, 32.75%, and 43.18% for LSC, SSC and IR regions, respectively. The cp genome encoded 113 unique genes .The complete chloroplast genome of E. jinchengshanense clustered with E. ilicifolium (NC_044897) with a moderate bootstrap value 85% (Epimedium species were of morphological similarity of flowers and leaves, and they were distributed in the adjacent geographical areas, which might explain the close relationship between E. jinchengshanense and E. ilicifolium.Phylogenetic analysis showed that alue 85% . The twoY. X. and S. H. were involved in the conception and design; L. F. and X. H. contributed the sample collection; F. L. and C. W. performed the analysis and interpretation of the data; Y. X., L. F. and C. W. contributed the drafting of the paper; Y. X. and S. H. revised it critically for intellectual content. All authors were involved in the final approval of the version to be published. All authors agree to be accountable for all aspects of the work."} +{"text": "Scientific Reports 10.1038/s41598-020-76070-w, published online 05 November 2020Correction to: The Acknowledgements section in this Article is incomplete.\u201cWe thank staff of the Babraham Institute Experimental Unit and Biological Services Unit at the University of Sheffield for technical assistance. J.S. gratefully acknowledges support from the Motor Neuron Disease Association, the Medical Research Council UK, the Lady Edith Wolfson Fellowship Fund, the van Geest Foundation, the Rosetrees Trust, Alzheimer\u2019s Research UK, and the Psychiatry Research Trust. This work was partly funded by Motor Neuron Disease Association grants awarded to R.M. (SITraN/Apr13/983-797 and SITraN/Jul16/987-797) and to R.M. and J.W. (Mead/Jun16/900-790). J.J.P.A. is funded by a National Institute for Health Research Clinical Lectureship. J.W. was funded by a University of Sheffield PhD scholarship.\u201dshould read:\u201cWe thank staff of the Babraham Institute Experimental Unit and Biological Services Unit at the University of Sheffield for technical assistance. J.S. gratefully acknowledges support from the Motor Neuron Disease Association, the Medical Research Council UK (MR/K010611/1), the Lady Edith Wolfson Fellowship Fund, the van Geest Foundation, the Rosetrees Trust, Alzheimer\u2019s Research UK, and the Psychiatry Research Trust. This work was partly funded by Motor Neuron Disease Association grants awarded to R.M. (SITraN/Apr13/983-797 and SITraN/Jul16/987-797) and to R.M. and J.W. (Mead/Jun16/900-790). J.J.P.A. is funded by a National Institute for Health Research Clinical Lectureship. J.W. was funded by a University of Sheffield PhD scholarship.\u201d"} +{"text": "T.forsythia-positive patients than in T.forsythia-negative patients. T.forsythia/C. albicans double-positive patients exhibited significantly greater PISA values than did non-double-positive patients. Additionally, PISA values were significantly greater in T. forsythia//T. denticola/C. albicans triple-positive patients than in T. forsythia//T. denticola/C. albicans non-triple-positive patients (p = 0.02). Propensity score-matching was performed between periodontopathic bacteria-positive and -negative patients using propensity scores generated from clinical factors. Importantly, T.forsythia/T. denticola double-positive patients exhibited significantly greater PISA values than non-double-positive patients among 72 propensity score-matched patients. Our preliminary results highlight the importance of the presence of T.forsythia and T. denticola for periodontal inflammation severity in older Japanese people.The periodontal inflamed surface area (PISA) has been proposed for assessment of the total periodontal inflammatory status in people with periodontitis. This study was performed to investigate the associations of periodontopathic bacteria and candida with PISA in older people. We enrolled 100 patients aged \u2265 60 years who visited Hiroshima University Hospital. PISA and periodontal epithelial surface area (PESA) were calculated in each patient. Oral rinse samples were collected for DNA extraction. Periodontopathic bacteria and candida were detected by polymerase chain reaction. The mean values of PISA and PESA were significantly greater in Treponema denticola, Tannerellaforsythia, and Porphyromonasgingivalis are associated with severe periodontitis [P. gingivalis and T. denticola are present in subgingival plaque at deep periodontal pockets [Fusobacterium subspecies, Prevotella intermedia, Prevotella nigrescens, Peptostreptococcus micros, Campylobacter showae, Campylobacter gracilis, Campylobacter rectus, Streptococcus constellatus, and Eubacterium nodatum) [Aggregatibacter actinomycetemcomitans is an important pathogenic species associated with localized aggressive periodontitis [A dynamic balance between oral microorganisms and the host is critical for the maintenance of oral health . Periododontitis . Both P. pockets . Microbinodatum) . These rdontitis . In addidontitis ,7. ThereP. gingivalis, T. forsythia, and T. denticola) and Candida albicans with PISA in older people.The periodontal inflamed surface area (PISA) has been proposed for assessment of the total periodontal inflammatory status in people with periodontitis . PISA isIn this study, we enrolled 100 patients aged \u2265 60 years who visited Hiroshima University Hospital from 2018 to 2019 and received supportive periodontal maintenance therapy. No patients had oral lesions, such as oral cancer or pre-malignant lesion . In addition, no patients had oral pseudomembrane formation and erythematous or atrophic lesions, which are characteristic findings of oral candidiasis. No patients received antibiotics or anti-inflammatory drugs at the time of examination. The study protocol was approved by the Ethical Committee of Hiroshima University and all patients provided written informed consent to participate. A schematic diagram of this study is shown in Patients were asked to rinse their mouths with saline for 15 s, then expel the rinse samples into sterile plastic tubes. Collected samples were centrifuged and supernatants were decanted; the resulting pellets were stored at \u221280 \u00b0C. DNA was extracted using a PureLink\u2122 Microbiome DNA Purification kit , in accordance with the manufacturer\u2019s protocol.Probing depth and bleeding on probing were examined at six sites for each individual tooth using a periodontal probe . Bleeding on probing was considered positive when gingival bleeding was observed within 20 s after probing . ExaminaP. gingivalis, T. forsythia, T. denticola, and C. albicans were detected by PCR. The following previously reported PCR primer sets were employed in this study: P. gingivalis, 5\u2032-AGGCAGCTTGCCATACTGCG-3\u2032 (sense) and 5\u2032-ACTGTTAGCAACTACCGATGT-3\u2032 (antisense); T. forsythia, 5\u2032-GCGTATGTAACCTGCCCGCA-3\u2032 (sense) and 5\u2032-TGCTTCAGTGTCAGTTATACCT-3\u2032 (antisense); T. denticola, 5\u2032-TAATACCGAATGTGCTCATTTACAT-3\u2032 (sense) and 5\u2032-TCAAAGAAGCATTCCCTCTTCTTCTTA-3\u2032 (antisense); C. albicans, 5\u2032-TTTATCAACTTGTCACACCAGA-3\u2032 (sense) and 5\u2032-ATCCCGCCTTACCACTACCG-3\u2032 (antisense); and universal primers for the bacterial 16S ribosomal RNA gene, 5\u2032-CGCTAGTAATCGTGGATCAGAATG-3\u2032 (sense) and 5\u2032-TGTGACGGGCGGTGTGTA-3\u2032 (antisense) [\u00ae Green Master Mix was employed to amplify PCR products. Amplifications of PCR products were performed using an Eppendorf Mastercycler EP Gradient S Thermal Cycler . The PCR protocol was as follows: 95 \u00b0C for 2 min, followed by 30 cycles of 95 \u00b0C for 1 min, 58 \u00b0C for 1 min, and 72 \u00b0C for 1 min. PCR products were electrophoresed on 2% agarose gels with ethidium bromide and were detected using an ultraviolet transilluminator. The presence of PCR products of expected sizes was determined by comparison with a 100 bp DNA ladder .tisense) ,11,12. G2 test or Fisher\u2019s exact test was used to compare categorical variables between groups. Binomial logistic regression analysis was conducted using a forced entry method. Binomial logistic regression analysis was performed using the presence of periodontal bacteria/candida as the dependent variable and variables with a p-value of <0.20 in univariate analysis as independent variables. A propensity score-matched analysis was performed to eliminate the effects of clinical confounding factors. Propensity scores were calculated by logistic regression analysis of eight clinical parameters . IBM SPSS Statistics, version 24.0 was used for statistical analysis. To calculate the sample size of propensity score-matched patients required for paired t-tests, G*Power was used with an effect size of 0.5, 80% statistical power, and a significance level of 0.05. The minimum sample size required for paired t-tests was 34 patients per group. For all analyses, p < 0.05 was considered statistically significant.The Mann\u2013Whitney U test or Kruskal\u2013Wallis test was used to compare continuous numerical variables between groups. The \u03c7P. gingivalis, T. forsythia, T. denticola, and C. albicans are shown in P. gingivalis was detected in 56 (56.0%), T. forsythia was detected in 83 (83.0%), T. denticola was detected in 49 (49.0%), and C. albicans was detected in 39 (39.0%). p = 0.04). Moreover, PISA values were greater in patients with diabetes or hypertension than in patients without those comorbidities. However, no significant associations were found between PISA and clinical factors.Amplified PCR products indicating the presence of P. gingivalis than in patients without P. gingivalis; however, these differences were not statistically significant. PISA values were significantly greater in patients with T. forsythia than in patients without T. forsythia (p = 0.01). The mean values of PISA tended to be greater in patients with T. denticola than in patients without T. denticola; however, this difference was not statistically significant. PISA values were significantly greater in T. forsythia/T. denticola double-positive patients than in T. forsythia/T. denticola non-double-positive patients (p = 0.01). In addition, PISA values were significantly greater in P. gingivalis/T. forsythia/T. denticola triple-positive patients than in non-P. gingivalis/T. forsythia/T. denticola triple-positive patients (p = 0.03). Significant differences in PESA were found between T. denticola-positive and -negative patients (p = 0.02), between P. gingivalis/T. denticola double-positive patients and non-P. gingivalis/T. denticola double-positive patients (p = 0.02), between T. forsythia/T. denticola double-positive patients and non-T. forsythia/T. denticola double-positive patients (p = 0.02), and between P. gingivalis/T. forsythia/T. denticola triple-positive patients and non-P. gingivalis/T. forsythia/T. denticola triple-positive patients (p = 0.03).C. albicans and PISA or PESA values . Notably = 0.02) .T. denticola was significantly associated with PESA . The presence of P. gingivalis/C. albicans was significantly associated with the number of remaining teeth . Additionally, the presence of P. gingivalis/T. forsythia/C. albicans was significantly associated with the number of remaining teeth . However, no statistically significant relationship was observed between the presence of periodontal bacteria/candida and PISA.The results of binomial logistic regression analysis with the presence of periodontal bacteria/candida as dependent valuable are shown in T. forsythia-positive versus T. forsythia-negative group (15 patients), T. denticola positive versus T. denticola negative group (33 patients), P. gingivalis/T. denticola double-positive group versus P. gingivalis/T. denticola non-double-positive group (29 patients), P. gingivalis/T. forsythia/T. denticola triple-positive group versus P. gingivalis/T. forsythia/T. denticola non-triple-positive group (29 patients), P. gingivalis/C. albicans double-positive group versus P. gingivalis/C. albicans non-double-positive group (17 patients), T. forsythia/C. albicans double-positive group versus T. forsythia/C. albicans non-double-positive group (29 patients), T. denticola/C. albicans double-positive group versus T. denticola/C. albicans non-double-positive group (21 patients), P. gingivalis/T. forsythia/C. albicans triple-positive group versus P. gingivalis/T. forsythia/C. albicans non-triple-positive group (20 patients), P. gingivalis/T. denticola/C. albicans triple-positive group versus P. gingivalis/T. denticola/C. albicans non-triple-positive group (16 patients), T. forsythia/T. denticola/C. albicans triple-positive group versus T. forsythia/T. denticola/C. albicans non-triple-positive group (21 patients), and P. gingivalis/T. forsythia/T. denticola/C. albicans quadruple-positive group versus P. gingivalis/T. forsythia/T. denticola/C. albicans non-quadruple-positive group (16 patients). Therefore, these groups were not included in further analyses.Propensity score-matching was performed between periodontopathic bacteria-positive and -negative patients using propensity scores generated from eight clinical factors, as described in the Materials and Methods section. However, sample size requirements were not met for patients in the P. gingivalis, P. gingivalis/T. forsythia, and T. forsythia/T. denticola with PISA were investigated in propensity score-matched patients. None of the eight clinical variables were significantly associated with the presence of periodontopathic bacteria .T. forsythia/T. denticola double-positive group than in the T. forsythia/T. denticola non-double-positive group. Additionally, PISA values tended to be greater in the P. gingivalis/T. forsythia double-positive group than in the P. gingivalis/T. forsythia non-double-positive group, but this difference was not statistically significant. These results suggest that co-infection with T. forsythia and T. denticola is a critical factor associated with chronic periodontal inflammation in Japanese older people.Significant correlations have been found between PISA and the severity of periodontitis or periodontal indexes in systemically healthy patients with periodontitis . To the T. denticola is periodontal pathogen that contributes to the severity of periodontitis by enhancement of alveolar bone resorption [T. denticola has several virulence factors such as dentilisin [T. denticola plays a role in bacterial adherence to epithelial cells and components of the extracellular matrix [T. forsythia has a variety of notable virulence factors, including Bacteroides surface protein A [T. forsythia is frequently present along with P. gingivalis in patients who exhibit active periodontitis [T. forsythia is accelerated when it is co-cultured with F. nucleatum [T. forsythia lipopolysaccharide was weakened upon co-culture with P. gingivalis [T. forsythia is affected by co-infection with other periodontopathic bacteria. Lanza et al. reported that T. denticola was associated with greater gingival bleeding, while T. forsythia was associated with chronic periodontitis severity, suggesting that T. denticola and T. forsythia may be the main red complex members involved in periodontitis progression [sorption . T. dentntilisin , the majntilisin , and facntilisin , which hr matrix . Additiorotein A , a trypsrotein A , glucosirotein A , forsythrotein A , and hemrotein A . T. forsdontitis ,25. The ucleatum . Notablyngivalis . These rgression .Candida species include extracellular hydrolytic enzymes [C. albicans-produced metallopeptidase presumably aids in periodontitis progression by degrading the extracellular matrix [T. forsythia/C. albicans double-positive group than in the T. forsythia/C. albicans non-double-positive group. Additionally, T. forsythia//T. denticola/C. albicans triple-positive patients showed significantly greater PISA values than non-triple-positive patients. Although the biological association between periodontopathic bacteria and C. albicans remains unknown, C. albicans may enhance periodontal inflammation in the presence of periodontopathic bacteria.Virulence factors present within agulase) . Phosphoagulase) . C. albir matrix . In thisThe presence of inflamed and ulcerated subgingival epithelium in the periodontal pocket provides the opportunity for bacterial endotoxins to disseminate into the bloodstream, which triggers inflammatory processes and the impairment of distant organs . Thus faThis study had an important limitation in terms of the sampling method; namely, oral rinse samples contain bacteria derived from various sites in the oral cavity. Thus, subgingival plaque and crevicular fluid samples may be more appropriate to determine the presence of periodontopathogens in the periodontal pocket. Further studies are needed regarding the relationship between periodontopathogens and periodontal inflammation to enable generalization of our findings.T. forsythia/T. denticola co-infection was significantly associated with greater PISA values in older Japanese people after adjustment for potentially clinical confounding factors using a propensity score-matching method. T. forsythia and T. denticola are involved in chronic periodontal inflammation in older people. The preliminary results in this study highlight the important roles of several periodontal pathogens in severe periodontal inflammation in older people. However, the impact of oral dysbiosis on periodontal inflammation has not been fully elucidated. Therefore, further studies should focus on clarifying the associations of oral microbiota with PISA."} +{"text": "Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults\u2019 infection, elite control has been rarely characterized in the pediatric population.We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents.+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B\u221727/57/81.PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor.Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8 HHSN261200800001E]. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research.V.A.V. and P.G. wrote the article, contributed to the study conception and design, and contributed to the acquisition, analysis, and interpretation of the data; E.A., J.M., J.R., C.F.G., D.P., B.T., M.P.M., and M.C.G. contributed to the acquisition of the data; M.M., C.B., J.M.P., A.B., M.C., G.T.W., and J.F. contributed with acquisition and interpretation of the data.None declared."} +{"text": "Epeorus (Caucasiron) hyrcanicussp. nov., is described based on larval morphology and molecular data (COI) containing sequences from all Caucasian Caucasiron species described to date. The species is distributed in the Hyrcanian forest of southeastern Azerbaijan and northwestern Iran. Based on our wide-range sampling, the new species is likely endemic to this area. The most pronounced larval morphological diagnostic characters are the coloration pattern of abdominal sterna and terga , poorly developed projection of the costal margin of gill plates III, presence of hair-like setae on the surface of abdominal terga, and relatively wide shape of gill plates VII . The diagnostic characters are compared to related species, and primary information to habitat is provided.A new species, Epeorus Eaton, 1881 s.l. is one of the most diverse mayfly genera in the Caucasus region. Except for a single representative of Epeorus s.str., Epeorus (Epeorus) zaitzevi Tshernova 1981, all Epeorus species distributed in the region belong to the subgenusCaucasiron Kluge, 1997 (hereinafter Caucasiron).Caucasiron includes the eastern Mediterranean islands (Samos and Cyprus), Turkey, the Caucasus, Iraq, Iran, Central Asia , and south-western China (Guizhou province) caucasicus , E. (C.) znojkoi , E. (C.) nigripilosus , E. (C.) magnus , E. (C.) alpestris , E. (C.) soldani , E. (C.) sinitshenkovae , E. (C.) iranicus , E. (C.) longimaculatus , E. (C.) insularis , E. (C.) bicolliculatus Hrivniak, 2017, E. (C.) turcicus Hrivniak, T\u00fcrkmen & Kazanc\u0131, 2019, E. (C.) alborzicus Hrivniak & Sroka, 2020, E. (C.) shargi Hrivniak & Sroka, 2020, and E. (C.) zagrosicus Hrivniak & Sroka, 2020. However, a recent molecular study of Caucasian Caucasiron by Caucasiron in the Caucasus could be higher. The morphology of these lineages was not examined in detail, and these taxa were, therefore, left without formal description.Currently, the following species are known from the Caucasus and adjacent areas , 2020b: Caucasiron sp. 3 by In this study, we provide a detailed morphological investigation and description of the lineage labelled as This species is distributed in the Hyrcanian forest of southeastern Azerbaijan and northwestern Iran Fig. . The forE. (C.) iranicus, E. (C.) alborzicus, and E. (C.) shargi shargi , 2020b.E. (C.) caucasicus, E. (C.) nigripilosus, and E. (C.) turcicus, and its origin is dated to the Pliocene apply molecular species delimitation methods to our COI dataset containing all currently described Caucasian Caucasiron species, and iii) provide diagnostic characters for identification of the new species together with basic information on its habitat requirements.The main aims of this study are to: i) investigate larval morphology of the lineage Caucasiron species, used for morphological comparisons and molecular analyses, were obtained from the collections of the Biology Centre of the Czech Academy of Sciences, Institute of Entomology, \u010cesk\u00e9 Bud\u011bjovice, Czech Republic (IECA).The material used for this study was collected by J. Bojkov\u00e1, T. Sold\u00e1n, and J. Imanpour Namin in Iran (May 2016), and \u013d. Hrivniak, P. Manko, D. Mur\u00e1nyi, and M. \u017diak in Azerbaijan (September 2018). Larvae were collected by hand net and preserved in 75\u201396% EtOH. Other Parts of larval specimens were mounted on microscopic slides using HydroMatrix mounting medium. In order to remove the muscle tissue for an investigation of the cuticular structures, specimens were left overnight in a 10% solution of NaOH prior to slide mounting. Drawings were made using an Olympus SZX7 stereo microscope and an Olympus BX41 microscope, both equipped with a drawing tube. Photographs were obtained using a Leica DFC450 camera on a Leica Z16 APO macroscope and stacked in Helicon Focus v. 5.3 X64. All photographs were subsequently enhanced with Adobe Photoshop CS5. Diagnostic characters for the description of larva were chosen according to COI) was sequenced according to COI sequences were obtained from seven specimens (three from Iran and four from Azerbaijan). COI sequences of other Caucasiron species were obtained from KY865691\u2013KY865725), KY865691\u2013KY865725), and MN856180\u2013MN856198). The PCR amplification of COI and reaction volumes was carried out as described in http://www.geneious.com) and aligned in the same software using the Mafft v. 7.017 according to the manufacturer\u2019s protocol. Mitochondrial cytochrome oxidase subunit I (v. 7.017 plugin wCOI) coalescence based General Mixed Yule Coalescent model . An ultrametric COI gene tree was reconstructed in BEAST 2 (http://wwwabi.snv.jussieu.fr/public/abgd/) with default settings.Inter- and intra-specific uncorrected pairwise genetic distances were calculated in MEGA X . Distance-based species delimitation was performed using Automatic Barcode Gap Discovery (ABGD) hyrcanicus sp. nov. is attributed to the subgenusCaucasiron within the genus Epeorus s.l. based on the following larval morphological characters: i) projections on the costal rib of gill plates II\u2013VII, ii) presence of medio-dorsally directed hair-like setae located on the anterior margin of the head (see subgenusCaucasiron).Holotype: female larva: Azerbaijan, L\u0259nk\u0259ran Province, NW of Azaru village, unnamed brook (left tributary (LT) of Vasharu River); 38.5873689N, 48.5870392E ; 1028 m a.s.l.; \u013d. Hrivniak, M. \u017diak leg., 21.9.2018. Paratypes: 5 larvae : same data as holotype.38.4824842N, 48.6243081E ; 734 m a.s.l.; \u013d. Hrivniak, P. Manko leg., 21.9.2018.1 larva (mounted on slide): Azerbaijan, L\u0259nk\u0259ran Province, SW of Sim village, unnamed brook (tributary of Digo River); LT of Shafa-rud River); 37.5294444N, 48.7552778 E ; 1345 m a.s.l.; J. Bojkov\u00e1, T. Sold\u00e1n, J. Imanpour Namin leg., 15.5.2016.4 larvae : Iran: Gilan Province, NW of Sangdeh village, unnamed brook ; 314 m a.s.l.; J. Bojkov\u00e1, T. Sold\u00e1n, J. Imanpour Namin leg., 16.5.2016.1 larva : Iran, Gilan Province, S of Tushi village , Shamrud River (RT of Sefid-rud River); 4 larvae : same data as holotype.38.2888889N, 48.8597222E ; -4 m a.s.l.; J. Bojkov\u00e1, T. Sold\u00e1n, J. Imanpour Namin leg., 19.5.2016.1 larva : Iran, Gilan Province, W Chelvand village (S of Lavandvil village), Chelavand River (about 2.5 km from its mouth); The name refers to the distribution of the species in the Hyrcanian forest.E. (C.) znojkoi.The species is distributed in northwestern Iran and southeastern Azerbaijan Fig. at -4 ton = 1); cerci broken. Body length of female mature larvae unknown.General coloration of larvae yellowish-brown, with dark brown to reddish maculation. Body length of male mature larva 8.25 mm ; sparse longer hair-like setae along pro-, meso- and metanotal suture.Legs. Colour pattern of femora as in Figure Abdominal terga. Colour pattern of abdominal terga and a pair of stripe-like (or elongated triangular) medio-lateral maculae joined to medio-anterior sigilla hyrcanicus sp. nov. are as follows: (i) abdominal sterna II\u2013VI with pair of oblique stripes fepes Fig. , (vi) fipes Fig. , (v) poopes Fig. ; arrow, pes Fig. ; 5H\u2013K.GMYC species delimitation model applied to COI gene tree provided significantly better fit for a speciation branching than null model suggesting uniform coalescent branching across the entire tree (likelihood ratio test = 6.258895e-07***). The GMYC estimated 16 species (CI = 11\u201318) consisting of 15 ML clusters and one singleton (E. (C.) insularis). Morphologically defined E. (C.) hyrcanicus sp. nov. was delimited as a distinct species based on both GMYC and ABGD species molecular delimitation analyses. All species clusters were highly supported hyrcanicus sp. nov. reached up to 1.75%. The minimum (and mean) interspecific distances between E. (C.) hyrcanicus sp. nov. and other Caucasiron species ranged between 8.11% nigripilosus) and 15.52% alpestris).The intraspecific pairwise genetic distances between specimens of E. (C.) hyrcanicus sp. nov. from all Caucasiron species known so far, some of the species distributed in the Caucasus and adjacent areas possess nearly identical states of some characters. Distinguishing of E. (C.) hyrcanicus sp. nov. from these species is described in detail below.Although the combination of larval morphological diagnostic characters listed above clearly determine E. (C.) hyrcanicus sp. nov. the most similar to E. (C.) caucasicus (widely distributed in the Caucasus), E. (C.) iranicus (distributed in Alborz Mountains), and E. (C.) zagrosicus (distributed in Zagros Mountains). The pattern of all these species consists of a pair of oblique stripes (medio-anterior sigilla). E. (C.) hyrcanicus sp. nov. usually exhibits oblique stripes together with a pair of stripe-like (or elongated triangular) medio-lateral maculae caucasicus and E. (C.) iranicus without such maculation hyrcanicus sp. nov., i.e. without distinctly pigmented medio-lateral maculae on abdominal sterna II\u2013VI caucasicus and E. (C.) iranicus. Such specimens are identifiable by the triangular shape of medial maculae on abdominal terga V\u2013VII hyrcanicus sp. nov., E. (C.) caucasicus bears crown-like medial maculae on terga V\u2013VII (E. (C.) iranicus stripe-like medial maculae with distinct antero-lateral stripes zagrosicus are anteriorly widened (E. (C.) hyrcanicus sp. nov.The oblique stripes on abdominal sterna II\u2013VI in E. (C.) hyrcanicus sp. nov., the coloration pattern of abdominal terga V\u2013VII, legs, and shape of gill plates VII is similar to E. (C.) shargi (distributed in the eastern Alborz Mountains) (E. (C.) hyrcanicus can be distinguished by the presence of the coloration pattern on abdominal sterna II\u2013VI shargi, where the pattern is missing (E. (C.) hyrcanicus sp. nov. shargi with well-developed projection (E. (C.) hyrcanicus usually bears short postero-lateral projection on tergum X shargi without such projection (In untains) : fig. 43\u2013VI Fig. , in contov. Fig. ; arrow am X Fig. ; arrow, E. (C.) soldani . Epeorus (C.) hyrcanicus sp. nov. can be separated from E. (C.) soldani by hair-like setae on abdominal terga soldani (E. (C.) hyrcanicus sp. nov., in contrast to E. (C.) soldani with narrow shape (E. (C.) hyrcanicus sp. nov., in contrast to E. (C.) soldani with well-developed projection (Well-defined triangular medial maculae on abdominal terga V\u2013VII are characteristic also for rga Fig. , in contow shape : fig 19L"} +{"text": "This article provides an overview of some problems of the breeding and reproduction of laboratory minipigs. The most obvious of these are the lack of centralized accounting of breeding groups, uniform selection standardsfor reproduction and evaluation of breeding animals, as well as minimizing the accumulation of fitness-reducingmutations and maintaining genetic diversity. According to the latest estimates, there are at least 30 breeding groupsof mini-pigs systematically used as laboratory animals in the world. Among them, there are both breed formationsrepresented by several colonies, and breeding groups consisting of a single herd. It was shown that the main selectionstrategy is selection for the live weight of adults of 50\u201380 kg and the adaptation of animals to a specific type of biomedical experiments. For its implementation in the breeding of foreign mini-pigs, selection by live weight is practicedat 140- and 154-day-old age. It was indicated that different herds of mini-pigs have their own breeding methods tocounteract inbred depression and maintain genetic diversity. Examples are the maximization of coat color phenotypes, the cyclical system of matching parent pairs, and the structuring of herds into subpopulations. In addition,in the breeding of foreign mini-pigs, molecular genetic methods are used to monitor heterozygosity. Every effort ismade to keep the number of inbred crosses in the breeding of laboratory mini-pigs to a minimum, which is not alwayspossible due to their small number. It is estimated that to avoid close inbreeding, the number of breeding groupsshould be at least 28 individuals, including boars of at least 4 genealogical lines and at least 4 families of sows. Theaccumulation of genetic cargo in herds of mini-pigs takes place, but the harmful effect is rather the result of erroneousdecisions of breeders. Despite the fact that when breeding a number of mini-pigs, the goal was to complete the herdswith exclusively white animals, in most breeding groups there is a polymorphism in the phenotype of the coat color Despite the practicality of laboratory use in comparison withprimates and several morphophysiological advantages overother laboratory animals , mini-pigs are still not the most popular biologicalmodel, second not only to rodents but also to dogs, cats andmonkeys . However, accordingto various estimates, there are from 21 to 45 breeding groupsof mini-pigs globally , ofwhich two are bred in Russia . Although, despite the importance of understanding the breeding of any animal species, regardless of their use,the problems of breeding laboratory mini-pigs are shown ina fairly small number of scientific papers. The apparently insufficient attention to the breeding and selection of mini-pigsresulted in some problems and the lack of a unified conceptfor their solution. The main ones are:the lack of centralized accounting of the number of laboratory mini-pigs and the registration system of specializedherds as breeding achievements;the lack of generally accepted standards for the selectionof animals for reproduction. This also includes the lackof regulatory documents for the evaluation of breedinganimals;maximizing herds\u2019 genetic diversity under conditions ofgene pool depletion vectors ,optimization of monitoring and selection managementmethods;minimizing the accumulation of fitness-reducing mutations;the creation of herds of laboratory mini-pigs, staffed exclusively from animals of white coat color;The purpose of this paper is to describe the listed problemsand suggest some ways to solve them.https://americanminipigassociation.com). However,out of 14 registered breeds, only four breeding groups werereliably used as laboratory animals.To date, it is difficult to estimate the number of the world\u2019spopulation of laboratory mini-pigs and the exact number oftheir breeds, herds, and breeding groups. The main difficultylies in the absence of a single body for recording laboratorymini-pigs as objects of breeding. For example, according toRussian legislation, the registration of laboratory mini-pigs isdifficult due to their formal non-compliance with the criteriafor evaluating breeds and breed groups of pigs as breedingachievements, particularly according to the uniformity of thebreeding stock . Nospecial standards have been developed for them. Registrationis possible on the website of the American Mini-pig Association .One of the reasons for the discrepancy in the calculation resultsis the presence of more than one name for the same breedformation. Our own count of laboratory mini-pigs indicated31 breeding groups in the world (Table 1). Both breed formations are represented by several colonies and breeding groups consisting ofa single herd . Representatives of the species Sus scrofa L. were taken into accountwith a live weight of no more than 150 kg and an indicationof systematic use as a model object over the past 10 years.1, which inthe defunct selection group Minisibs had such consequencesas lowering the safety of piglets, sexual activity of boars anddestroying the complex of maternal qualities of sows .In the breeding of laboratory mini-pigs, there are two mainselection vectors: for small size and low live weight and suitability for laboratory use. However, in the breeding of minipigs, there are no uniform specially developed standards forevaluating animals by live weight at an early age, exterior, coatcolor and a set of characteristics necessary for use in the mostcommon types of biomedical experiments .Simultaneously, almost every herd has a systematic approachto breeding with its own specific methods . Animals are often evaluated at an earlyage, for example, 140\u2013154 days . Some private farms practiceselection of the smallest animals from each nesthttps://www.farmersweekly.co.za/animals/pigs-as-pets-breeding-teacup-pigs/Erasmus D. Pigs as pets: Breeding teacup pigs. Farmer\u2019s Weekly. 2013. The only general principle is selecting the most robust,healthy and proportionally developed animals with a liveweight of adults from 50 to 80 kg .Vietnamese mini-pigs\u2019 exterior traits such as a weak back orearly obesity are not welcomed by Russian, European andAmerican specialists. Russian mini-pigs and several foreignbreeding groups meet the accepted standards, but there aredeviations, both in larger and smaller directions (Table 2).Recently, the breeding of herds of tiny pigs weighing 30\u201350 kg, for example, German mini-pigs Aachen, American Panepinto and Korean Micro-Pig\u00ae, is gaining popularity (seeTable 2).The problem of preserving genetic diversity in populations isone of the most discussed issues in animal genetics and, for several reasons, is particularlyrelevant for laboratory mini-pigs. The first reason is the lowpopulation of herds. The risk of depletion of the gene pooldue to stochastic processes is significantly higher than in largestructured subpopulations communities .The second reason is the existence of several breeding groupsof laboratory mini-pigs in the singular, which deprives themof such a powerful resource for controlling heterozygosityas the periodic exchange of the gene pool between differentherds . The third reason is that creatingnew herds of laboratory mini-pigs from a small number ofprogenitors (see Table 1) creates a risk of depleting the gene pool due to the bottleneck effect . Interestingly,according to various estimates, the genetic diversity of laboratory pigs can be both greater and lower compared with similarparameters of pigs of factory breeds and wild boar .Several publications mentioned the existence of natural\u201ccontr inbred\u201d mechanisms in natural populations ,which is indirectly confirmed by the existence of the shortpopulations of feral pigs with no signs of inbreeding depression on small islands throughout the centuries . In the conditions of farmsfor breeding of laboratory mini-pigs, the formation of thecomposition of the reproductive group and the choice of parent pairs during the breeding campaign is carried out by thebreeder. Therefore, the question about the full functioning ofsuch mechanisms arises. Thus, there is a need to analyze themethods available to humans to control herds\u2019 heterozygosityof laboratory mini-pigs. The first method is monitoring geneticdiversity using molecular genetic methods, which is used toselect some of the mini-pigs . A limitingfactor in further implementing this method is the lack of dataon its economic feasibility in routine use.The second way to control heterozygosity is to use breeding techniques and methods, for example, to minimize inbredcrosses . In the breeding of mini-pigsof the ICG SB RAS, the conservation of the maximum possible number of color phenotypes and inbreeding mainly onthe progenitors is used to preserve genetic diversity . Given that the mammalian suit is controlledby 120 to 350 genes , the number of possible genotypes can be in thethousands. Another breeding method for maximizing genetic diversity is dividing an array of animals into subpopulations with a limited gene flow between them . However, due to the low number of rock formations,partial genealogical separation of lines, with rare exceptions, is practically impossible to implement. Instead, a cyclical selection system is practiced based on periodically repeatedcrosses of lines and families (Table 3). According to the calculations, to avoid close inbreeding, the minimum number ofthe reproductive group should be at least 28 individuals, ofwhich boars should be represented by at least four lines andsows \u2013 by four families. Each line should include at least onemain and one checked boar, and the family should consist ofat least 5 main and checked sows.In the 1970s, it was reported that in populations of less than2,000 individuals, the probability of accumulation of fitnessreducing mutations is quite high .Even earlier, it was established that recessive semi-lethal mutations could persist in a population for up to 99 generations evenwith targeted culling of homozygotes , which is generally not refuted by later mathematicalmodelling . It is considered that theelimination of harmful recessive mutations is a difficult taskfor the breeder, even if he uses modern genotyping methods. Given that the reproductive number ofindividual herds of laboratory mini-pigs does not exceed 30\u201340 individuals reducing sustainability, semi-lethal and lethalrecessive mutations pose a danger in breeding these animals.At the same time, in the entire history of breeding laboratorymini-pigs, only in the extinct breeding group Minisibs a decrease in the viability of young animals and the reproductivequalities of adults was described, the alleged cause of whichwas the accumulation of recessive mutations due to unilateralselection . Thus, laboratory mini-pigs\u2019breeding system should include measures to purify the herdfrom harmful mutations, leading to strict selection in the reproductive group . Another methodof cleaning herds from unwanted mutations is to assess theprogeny in the inbred cross. This method was proposed forvarious farm animals\u2019 species in the 1950s and 1970s . However, despite itssimplicity, the method has a serious drawback \u2013 it is the duration of the assessment and, accordingly, the cost of feedingand maintaining the tested boar and its descendants.However, there are cases where breeders have benefitedfrom the emergence of viability-reducing mutations in theherd in the form of creating model objects to optimize specific medical methods or treat strictly defined pathologies.Examples are the creation of mini-pigs by MeLiM and NIH. Thus, it can be arguedthat the very fact of the occurrence of mutations that reduceviability, of course, is a danger. But much more importantis breeders\u2019 ability to prioritize the selection of animals forreproduction and to carry out measures to clear the herds ofgenetic cargo; and if necessary, to consolidate the carriers ofmutations in the form of a new selection group that is of valueas a model object.It is known that when creating the first breeding groups oflaboratory mini-pigs, the task was to create white-coloredanimals , which were planned to be usedas a biological model for studying the effects of radioactiveradiation on the skin. However, despite the \u201cinflux of blood\u201dof factory breeds of white color, attempts to consolidate it inherds of laboratory mini-pigs, as a rule, did not succeed. Theexceptions are the Mini-Lewe pigs and the Bintang line (Lanyu 400) in the Lanyu mini-pig breeding group , but most herds have polymorphismby suit type . Thus, the question arises aboutthe factors that prevent the breeding of herds fully equippedwith white individuals. It can be assumed that this is due tothe dominant control of the most common type of white coatcolor , which is why there is a regularcleavage of pigmented piglets. Another explanation is thatwhite piglets are born smaller and, therefore, less viable thancolored animals . Despite this, the whitecoat color was successfully consolidated in a factory breedsseries . It should be noted that the factorybreeds of white-colored pigs were obtained by the method ofmore than 70 years of selection of white individuals in eachgeneration with a preference for those animals in whose offspring there was no splitting according to the color phenotype. And this, in turn, is comparable to theduration of the oldest breeding groups of laboratory mini-pigs. Thus, it can be assumed that the breedersof most breeding groups of mini-pigs simply did not haveenough time to consolidate the white suit.Molecular genetic typing of white animals would significantly speed up the process of fixing the white suit. It isknown that the dominant white color of pigs is controlled byallele I of the KIT gene .Thus, the first step to create a breeding group complete withall-white animals should be to cross white sows with white boars. All-white offspring from such crosses will need to begenotyped according to the KIT gene with the setting of homozygotes (I/I\u200a) for rearing. The method of determining theKIT gene\u2019s alleles using real-time PCR is described in detailin the literature .Another way is to consolidate the recessive white suit\u2019sphenotype, as demonstrated by the Lanyu 400 line and the Chinese Rongchang breed .However, a rather serious restriction on using this methodmay be the low frequency of cleavage of recessive white colorindividuals, which in the herd of mini-pigs of the Institute ofCytology and Genetics SB RAS, according to zootechnicalaccounting, is about 1 %.Over the past 10 years, facts have been discovered confirmingthe existence of 31 breeding groups of mini-pigs. Despite thelack of uniform selection standards in breeding laboratorymini-pigs, they adhere to such general criteria as a live weightof 50\u201380 kg, normal viability, and the strength of the animals\u2019constitution and exterior. Maintaining genetic diversity inherds of laboratory mini-pigs is possible both with the use ofmolecular genetic monitoring and purely selective methods.The minimization of the negative effect of genetic cargo accumulation in the herds of mini-pigs should be implementedmainly through a strict selection for fitness in the reproductive group. If necessary, due to the need for a specific typeof biomedical experiments, it is possible to fix external andphysiological characteristics in the herd, controlled by recessive mutations that reduce viability. Consolidation of whiteindividuals is possible, which is proved by the examples ofthe Bintang line and the Mini-Lewe breeding group.The authors declare no conflict of interest.Bourneuf E. 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Moscow: Nauka Publ., 1970. (inRussian)Shatokhin K.S., Nikitin S.V., Knyazev S.P., Goncharenko G.M., Ermolaev V.I., ZaporozhetsV.I. Livestock, physiology, and geneticsof the mini-pigs of the Institute of Cytology and Genetics. Novosibirsk: Institute of Cytology and Genetics, 2019. (in Russian)Simianer H., K\u00f6hn F. Genetic management of the G\u00f6ttingen Minipig.J. Pharmacol. Toxicol. Methods. 2010;62:221-226. DOI 10.1016/j.vascn.2010.05.004.Simon C. Fachinformation aus dem Ausschuss f\u00fcr Ern\u00e4hrung der Versuchstiere. F\u00fctterungskonzepte und -methoden in der Versuchstierhaltung und im Tierversuch \u2013 MINIPIG. Basel Reinhart Kluge,Potsdam-Rehbr\u00fccke. 2019;11. (in Germany). Available at: https://docplayer.org/170135602-Fachinformation-aus-dem-ausschussfuer-ernaehrung-der-versuchstiere.html.Smith A.C., Swindle M.M. Preparation of swine for the laboratory.ILAR J. 2006;47(4):358-63. DOI 10.1093/ilar.47.4.358.Song T., Wu T., Wei F., Li A., Wang F., Xie Y., Liu D., Fan Z.,Wang X., Cheng S., Zhang C., He J., Wang S. Construction ofa cDNA library for miniature pig mandibular deciduous molars.BMC Dev. Biol. 2014;14:16. DOI 10.1186/1471-213X-14-16.Stankova N.V., Savina M.A., Kapanadze G.D. The formation of newlines of Svetlogorsk minipigs. Biomeditsina = Biomedicine. 2017;3:95-101. (in Russian)Tikhonov V.N. Laboratory Minipigs. Genetics and Biomedical Use.Novosibirsk: Publishing House SB RAS, 2010. (in Russian)Val-Laillet D., C\u00e9line Tallet C., CaroleGu\u00e9rin C., Meunier-Sala\u00fcn M.-C. Behavioural reactivity, social and cognitive abilities ofVietnamese and Pitman\u2013Moore weaned piglets. Appl. Anim. Behav. Sci. 2013;148:108-119. DOI 10.1016/j.applanim.2013.06.003.Wu Z., Deng Z., Huang M., Hou Y., Zhang H., Chen H., Ren J.Whole-Genome Resequencing Identifies KIT New Alleles ThatAffect Coat Color Phenotypes in Pigs. Front. 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DOI 10.18805/ijar.7494."} +{"text": "Pedicularis siphonantha complex, endemic to the Mountains of Southwest China. This complex is characterized by its red/purple/pink and long-tubular corolla, and twisted, beaked galea. However, herbarium specimens are often difficult to identify to species. Molecular approaches using nrITS or nuclear ribosomal internal transcribed spacer (nrITS) + plastid DNA (ptDNA) have been successfully used for species identification in Pedicularis. To resolve taxonomic confusion in the Pedicularis siphonantha complex, we reconstructed phylogenies of the complex using nrITS and four plastid DNA loci . To recover as much of the phylogenetic history as possible, we sampled individuals at the population level. Topological incongruence between the nrITS and ptDNA datasets was recovered in clades including two widely distributed species, Pedicularis milliana and Pedicularis tenuituba. Based on morphological, geographical, and genetic evidence, we suggest that hybridization/introgression has occurred between P. milliana and Pedicularis sigmoidea/Pedicularis sp. 1 in the Yulong Snow Mountain of Lijiang, northwest Yunnan, and between P. tenuituba and Pedicularis leptosiphon in Ninglang, northwest Yunnan. After removing conflicting DNA regions in Pedicularis dolichosiphon (nrITS) and P. milliana (ptDNA), the concatenated nrITS and ptDNA phylogenies distinguish 11 species in the P. siphonantha complex, including two undescribed species, from the Jiaozi and Yulong Snow Mountains, respectively. Phylogeographical analyses indicate that the P. siponantha complex originated from south of the Hengduan Mountains, expanding north to the Himalayas and the Yunnan-Guizhou Plateau. Moreover, the uplift of the Qinghai-Tibet Plateau and climate oscillations may have driven further diversification in the complex.Morphological approaches often fail to delimit species in recently derived species complexes. This can be exacerbated in historical collections which may have lost key features in specimen preparation and preservation. Here, we examine the Meconopsis Vig. (Papaveraceae), Primula L. (Primulaceae), and Rhododendron L. (Ericaceae) . Speciesicaceae) . The stuPedicularis L. (Orobanchaceae) consists of approximately 600\u2013800 species, of which two-thirds are endemic to the Mountains of Southwest China short-tubular corolla with a beakless, toothless galea (upper lip), (B) short-tubular corolla with a toothed galea, (C) short-tubular corolla with a beaked galea, and (D) long-tubular corolla with a beaked galea P. C. Tsoong. In contrast, P. delavayi as a separated species. Pedicularis tenuituba H. L. Li and Pedicularis milliana W. B. Yu et al. as P. delavayi , no samples of P. delavayi cluster with other species of the P. siphonanta complex. P. delavayi as a separate species and discovered an undescribed species, P. milliana, which was previously misidentified as P. siphonantha var. delavayi or P. delavayi. To date, species delimitation of the P. siphonantha complex is not fully resolved, due to limited sampling and poorly known species distributions with population-level sampling. Our main goals were to: (1) explore patterns and causes of phylogenetic incongruence between nrITS and plastid DNA datasets in the P. siphonantha complex; (2) revise species delimitations in the P. siphonantha complex; and (3) investigate the causes of species diversification in the P. siphonantha complex.In this study, we reconstructed a comprehensive phylogeny of the P. siphonantha complex and 12 other Pedicularis species of the 78 individuals, 50 were newly sampled and sequenced. There were 22 samples (19 populations) of P. tenuituba, widely distributed in western Sichuan, and 17 samples (14 populations) of P. milliana, endemic to the northwestern Yunnan. Three populations of P. milliana were collected from the Yulong Snow Mountain in Lijiang, and population F14 was collected from the Haba Snow Mountain in Shangri-La. In addition, population G , collected from Ganheba in the Yulong Snow Mountain represents an unknown taxon, which is similar to P. sigmoidea in the shape of the galea beak but has a smaller corolla. Populations E1\u2013E3, collected from the Jiaozi Snow Mountain, represents another unknown taxon, which is distinguished from P. milliana by its oblate and crested beak. The remaining six taxa of the P. siphonantha complex have narrow distributions, so only a few individuals/populations were included in this study. We included nine samples (seven populations) of P. delavayi from the northwestern Yunnan and western and northern Sichuan, where it overlaps with P. milliana and P. tenuituba. Geographic information for all samples the P. siphonantha complex is shown in We sampled 78 individuals, mainly from the Hengduan Mountains, as well as the Himalayas and the Yunnan-Guizhou Plateau, representing 11 taxa of the species . The 11 matK, rbcL, trnH-psbA, and trnL-F) were amplified and sequenced in this study. Primer information of five DNA markers were presented in previous studies (P. milliana F2/03-060) had two ambiguous basecalls , and three samples had one basecall. The ambiguous site was assigned using IUPAC ambiguity characters. Assembled sequences were aligned using MAFFT 7.4 markers were partitioned by gene and the best-fit model was estimated using Modeltest-ng (Both Bayesian Inference (BI) and maximum likelihood (ML) were used to reconstruct phylogenetic relationships in the ltest-ng H. L. Li and the four ptDNA regions of the samples F11\u2013F14 of P. milliana were identified as heterogeneous sequences, so that those sequences were removed from the concatenated nrITS + ptDNA dataset. Then, the concatenated nrITS + ptDNA phylogeny was performed using the same methods as nrITS and the concatenated ptDNA phylogenetic analyses (see above). Additionally, the Shimodaira\u2013Hasegawa (SH) test test and the SH) test were useSH) test , and theSH) test .P. siphonantha complex and two outgroups Pedicularis amplituba H. L. Li and Pedicularis tachanensis Bonati, was imported into BEAUti with \u201cbeast-classic package\u201d collected from Yadong country in the middle Himalaya were assigned to subregion IIIa. The sites model was calibrated using the \u201cbModeltest package\u201d . The two protein-coding genes (rbcL and matK) are less informative than the three spacer datasets. Sequences of P. siphonantha and P. milliana show the highest variation at the species level for both nrITS and ptDNA datasets.Matrix characteristics of nrITS, four plastid DNA, and the concatenated ptDNA datasets are shown in P. milliana sequences were significantly smaller (P < 0.05) than the distance between P. milliana and any other taxon, with one exception; nrITS sequences of P. milliana and Pedicularis sp. 1 did not differ significantly. The same pattern holds for P. tenuituba, with the exception being a non-significant distance with nrITS sequences P. dolichosiphon. While the ptDNA distances within P. siphonantha were significantly less than the distance between P. siphonantha and ptDNA of any other taxon, distances of nrITS sequences within P. siphonantha were significantly smaller than the distance between P. milliana and Pedicularis tahaiensis Bonati (P < 0.05).Comparisons of genetic distances within and between species using the K\u2013S test are shown in P. siphonantha complex was recovered as monophyletic (BS/PP = 95/1.00), and P. delavayi was not included in that clade. Within the P. siphonantha complex, five major clades were recovered. Clade I had only Pedicularis humilis Bonati, and it was moderately supported as sister to the remaining four clades (BS/PP = 63/0.95). The relationships among Clades II\u2013V were not well-resolved. Clade II consisted of three individuals of Pedicularis sp. 2, and clade III included two species, Pedicularis leptosiphon H. L. Li and P. siphonantha, with P. leptosiphon nested within P. siphonantha, although with weak support. Clades IV and V were weakly supported as sister lineages (BS/PP = 55/0.87). Clade IV consisted of five species, Pedicularis dolichantha Bonati, P. milliana, P. sigmoidea, Pedicularis variegata H. L. Li, and Pedicularis sp. 1 (G). In this clade, Pedicularis sp. 1 (G) was nested within P. milliana. Clade V consisted of P. dolichosiphon nested within 22 samples of P. tenuituba.Maximum likelihood and BI analyses obtained identical topologies for the nrITS dataset . The P. P. siphonantha complex was not recovered as monophyletic, including P. amplituba + P. tachanensis not considered here to be members of the complex. The core species of the P. siphonantha complex were split into two major clades , with Clade C (P. amplituba and P. tachanensis) weakly supported as sister to the remaining members of Clade B (BS/PP = 38/0.65). Clade A included four species, P. dolichosiphon, P. leptosiphon, P. siphonantha, and P. tenuituba, which were strongly supported as monophyletic (BS/PP \u2265 99/1.00). Within Clade A, P. siphonantha was sister to the remaining three species with P. dolichosiphon and P. leptosiphon forming a clade sister to P. tenuituba.Maximum likelihood and BI obtained identical topologies from the ptDNA dataset . Unlike P. dolichantha, P. sigmoidea, Pedicularis sp. 1, and four samples of P. milliana from the Yunlong Snow Mountain and the Haba Snow Mountain. In this subclade, P. dolichantha was sister to the remaining species, with P. sigmoidea as the sister to a clade including Pedicularis sp. 1 nested within P. milliana. The other subclade included P. humilis, P. variegata, Pedicularis sp. 2, and 13 samples of P. milliana, which were all supported as monophyletic. Within this subclade, P. variegata was sister to the remaining species, with P. humulis arising as sister to a clade including Pedicularis sp. 2 + P. milliana.Clade B contained seven species, which were split into two subclades. One subclade included P. milliana, P. tenuituba, and their relatives. In the nrITS phylogeny, 17 samples of P. milliana were only monophyletic if they included Pedicularis sp. 1 (BS/BP = 85/1.00). In the ptDNA phylogeny, they were separated into two distant clades, i.e., four samples (F11\u2013F14) formed a clade by including Pedicularis sp. 1 (BS/BP = 100/1.00) as sister to P. sigmoidea, and the remaining 13 samples were monophyletic (BS/BP = 96/1.00) as sister to Pedicularis sp. 2. Twenty-four samples of P. tenuituba are strongly supported as monophyletic (BS/BP = 99/1.00) in the ptDNA phylogeny, but they are made paraphyletic by the inclusion of P. dolichosiphon in the nrITS phylogeny. Therefore, the four ptDNA regions of P. milliana samples F11\u2013F14 and the nrITS sequence of P. dolichosiphon were identified as heterogeneous sequences. In addition, the nrITS dataset supports monophyly of the P. siphonantha complex (BS/BP = 95/100), but the ptDNA dataset does not, by including two short-tubular species P. amplituba and P. tachanensis.NrITS and ptDNA phylogenies are incongruent in the placement of P < 0.01) the best tree topology of the nrITS dataset and monophyly of P. milliana. These tests failed to reject the monophyly of P. tenuituba + P. dolichosiphon and monophyly of the P. siphonantha complex. Meanwhile, when constrained by the nrITS dataset, SH and AU tests failed to reject (P > 0.05) the monophyly of P. tenuituba + P. leptosiphon + P. siphonantha, and the monophyly of P. milliana + Pedicularis sp. 2, but rejected the best tree topology of the ptDNA dataset, and the short tubular P. tachanensis + P. amplituba clade sister to the Clade B. Moreover, for the modified nrITS + ptDNA dataset, the null hypothesis that short tubular P. tachanensis + P. amplituba is sister to Clade 2 was rejected (P < 0.05).Results of the AU and SH test for alternative hypotheses are summarized in P. dolichosiphon (nrITS) and P. milliana (ptDNA regions of F11\u2013F14), ML and BI analyses produced nearly the same topology included P. dolichosiphon, P. leptosiphon, P. siphonantha, and P. tenuituba. In this clade, P. siphonantha was sister to the remaining taxa, with the monophyletic P. tenuituba (BS/BP = 100/1.00) sister to a clade including P. dolichosiphon + P. leptosiphon (BS/BP = 100/1.00). Clade 2 (BS/BP = 95/1.00) included six taxa forming two subclades. In the larger subclade, P. milliana was monophyletic (BS/BP = 94/1.00), and sister to Pedicularis sp. 2 (BS/BP = 99/1.00). A clade including P. milliana + Pedicularis sp. 2 + P. variegata was sister to P. humilis (BS/BP = 65/0.93). In the other subclade, P. dolichantha was sister to P. sigmoidea + Pedicularis sp. 1 (BS/BP = 99/1.00).After removing conflicting sequences, topology . Within P. milliana split into two clusters (Pedicularis sp. 1 as sister to P. sigmoidea (BS = 96.8), and the other 13 samples were monophyletic as sister to Pedicularis sp. 2. In addition, P. dolichosiphon was resolved as either sister to P. leptosiphon (BS = 100) or P. tenuituba (BS = 85.6).The phylogenetic network of the concatenated nrITS and ptDNA dataset showed clusters , identicP. siphonantha complex diverged from other Pedicularis in the late Miocene (6.04Mya\u201310.38Mya), south of the Hengduan Mountains (IIb), which harbors nine of eleven species/taxa of this complex , P. leptosiphon and P. dolichosiphon diverged in situ (IIb), and P. tenuituba diverged north of the Hengduan Mountains. In Clade 2, seven species/taxa diverged in situ (IIb), with some populations of P. milliana migrating northward to IIIb and IIIc.Phylogeographical analysis indicated that the most common ancestor of the complex . SpeciesP. siphonantha complex and in the sister relationship between the P. siphonantha complex and P. amplituba + P. tachanensis in phylogenetic analyses, as well as the estimation of genetic distance. The incongruence could be caused by convergent sequence evolution, incomplete lineage sorting, hybridization/introgression, horizontal gene transfer, and gene duplication/loss and P. sigmoidea/Pedicularis sp. 1 (\u2642) in the Yulong Snow Mountain. In this scenario, high-altitude hybrids (\u2640) backcrossed with ancestors of P. milliana (\u2640), and low-altitude hybrids became established as species at lower altitudes. Therefore, morphological consistency was found among high-altitude populations of P. milliana, while low altitude Pedicularis sp. 1 diverged from P. milliana in the shape of the beak and low lip of corolla. Sample C of P. dolichosiphon might also be the result of introgression between P. tenuituba (\u2640) and P. leptosiphon (\u2642), but greater population-level sampling is required to investigate this fully. In addition, more genomic evidence from organelle and nuclear genomes were needed to test these speculations.Introgression might have been common within recently derived species complexes when their distributions overlap . Pediculommunity . In the P. siphonantha complex together with other long-tubular species belonged to Ser. Longiflorae . Therefore, the monophyly of the P. siphonantha complex should be accepted, but more nuclear genes and more robust phylogeny should be applied for evaluating this complex in the future.Traditionally, the giflorae . Phylogephyletic , 2018. IP. dolichosiphon and Pedicularis sp. 1, species delimitations of the remaining nine species are well-resolved, which is consistent with morphological identification. For Pedicularis sp. 2, the corolla beak shape and lower-lip lobes are quite different than its sister species, P. milliana. Moreover, Pedicularis sp. 2 occurs on the Jiaozi Snow Mountain. Morphological, molecular, and biogeographic evidence all support Pedicularis sp. 2 to be a new species. It is worth noting that relatively high intraspecies genetic and phenotypic variations suggest P. siphonantha in the Himalayas needs further investigations [also reviewed by P. humilis is still not well-resolved; however, it is an isolated species of the Gaoligong Mountain, perhaps the result of allopatric speciation.Although introgression may confound phylogenetic species delimitation of P. siphonantha complex. Because floral characters are labile in Pedicularis, morphologically similar species might be only distantly related. For example, phylogenetic analyses showed that P. milliana was clustered with morphologically different species including P. variegata, P. humilis, P. dolichantha, and P. sigmoidea, rather than the morphologically similar species P. siphonantha, contra previous placements [e.g., P. delavayi (excluded from the P. siphonantha complex) was clustered with short-tubular species Pedicularis obiquigaleata W. B. Yu and H. Wang. Understanding taxonomic affinities within the P. siphonantha complex requires morphological, geographical, and molecular evidence.Traditionally, morphological character similarity was the main evidence for assessing species relationships, but this criterion might be not suitable in the ts e.g., . MoreovePedicularis in the Mountains of Southwest China is thought to be associated with the uplift of the Qinghai-Tibet Plateau and the establishment of the Asian monsoon climatic cycle , rather than widely distributed in the eastern Himalaya, Sichuan, and Yunnan, as described in the Flora of China is only found in the Jiaozi Snow Mountain, Dongchuan, Yunnan. Of the seven species in this clade, P. milliana and Pedicularis sp. 1 co-occur in the Yulong Snow Mountain and P. sigmoidea has been collected from the south margin of the distribution range of P. milliana in Heqing, Eryuan, and Dali. Therefore, geographical isolation likely drove species divergence in this complex, with the exception that introgression between P. milliana and P. sigmoidea may have produced the suspected hybrid Pedicularis sp. 1 and the plastome capture of P. milliana from P. sigmoidea in Lijiang and south Shangri-La, northwest Yunnan.The mountainous terrain of the home range of the matK, rbcL, trnH-psbA, and trnL-F) clarify species delimitation within the P. siphonantha complex. Differences in geographical distribution and altitude can be important supplementary indicators to identify species of the P. siphonantha complex despite the lack of diagnostic morphological characters in herbarium specimens. The P. siphonantha complex likely originated from allopatric speciation. The origin of P. milliana and Pedicularis sp. 1 in the Lijiang region was plausibly due to an ancestral hybridization event. The morphological, molecular, and biogeographic evidence support taxonomic recognition of Pedicularis sp. 2. To better understand the evolution of the P. siphonantha complex, further studies of phenotype and environmental factors are needed.Overall, phylogenetic analyses of five DNA loci can be found in the article/W-BY, HW, and D-ZL conceived the study. W-BY, HW, J-BY, and RC collected the data. RL and W-BY analyzed the data. RL, W-BY, CR, and D-ZL interpreted the results. All authors wrote and revised the article and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer C-LX declared a shared affiliation, with no collaboration, with several of the authors HW, J-BY, and D-ZL to the handling editor at the time of the review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has beenpaid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides inlength; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currentlybeing conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs havebeen shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation.Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNAbiogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and seniledementia, which are often accompanied by deterioration in the learning ability and by memory impairment.Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interestin studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as wellas the latest achievements in studying the functional role of microRNAs in learning and in long-term memoryformation, depending on the activation or inhibition of their expression. The review presents summarized dataon the effect of impaired microRNA biogenesis on long-term memory formation, including those associated withsleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improvingcognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and activemental and physical exercises. The mechanisms of forming long-term memory (LTM) andof its improvement in case of impairment resulting fromtrauma, neurological and neurodegenerative diseases, andage-related dysfunctions are among the most challengingissues to be solved by the science. Back in the middle ofthe last century, researchers realized that LTM formationrequires active involvement of the genome. Later, it wasshown that newly synthesized proteins are necessary formodification of synaptic contacts and rearrangements ofthe neural networks involved in consolidating new experiences . The main difficulties in studying themolecular basis of LTM are associated with both complexityof the structure of the central nervous system and with variety of the regulatory processes acting at the genome level.The latter include regulation of gene expression by DNAbinding transcription factors, as well as epigenetic modifications that regulate the structure of chromatin . These epigenetic processes are widely involved inbrain functioning, including neuronal differentiation andadaptive behavior, inter alia LTM formation .Somewhat later, studies were started on involvement ofmicroRNA in the epigenetic regulation of gene expression.MicroRNAs are unique non-coding molecules, each ofwhich able to regulate translation of hundreds to thousandsof messenger RNAs (mRNAs) targets. MicroRNAs aremost widely represented in the central nervous system,and many of them are expressed at a high level . A large number of studies have been publishedon microRNAs participation in neuronal differentiation, in the LTM formation, as well as in the pathogenesis of diseases associatedwith mental disorders, neurodegenerative pathologies andsenile dementia . Optimistic predictionsare expressed that a number of microRNAs can be used astargets for therapeutic treatment and diagnosis of diseasesaccompanied by cognitive impairment .This important applied value of microRNAs raises interestin the study of their functions. This review will examine indetail the role of microRNAs in cognitive processes.For the first time, microRNAs, as functionally significantmolecules capable of regulating gene expression, were described in the nematode C. elegans in 1993 . In 2000, highly conserved microRNA let-7, whichis necessary for organism development, was discoveredin the same animal . In parallel, in1998, A. Fire and C. Mello published an article in whichit was shown that by means of small double-strandedRNAs (siRNA) it is possible to silence genes \u2013 this mechanism was called RNA interference. Moreover, already in2006, in view of the importance of this discovery, Andrew Fire and Craig Mello were awarded the Nobel Prizein Physiology or Medicine. It has been shown that genesilencing by means of RNA interference is also carried outby microRNA . Since the 2000s, anavalanche of studies on the functional role of microRNAand its biogenesis in many animal species startedMicroRNAs are a family of small, highly conserved endogenous non-coding RNAs about 22 nucleotides long . MicroRNA biogenesisis a complex and multistep process, including transcriptionfrom DNA of a rather long primary transcript (pri-miRNA)with characteristic stem-loop structures, its processing toform pre-miRNA, translocation of pre-miRNA into thecytoplasm and its further processing to form microRNA(miRNA). Next, the microRNA interacts with the RISCcomplex (RNA-induced silencing complex) in which themicroRNA binds to the target mRNA and induces degradation and/or mRNA translational repression . Evolutionarily conserved proteins control all of the above stages: DROSHA, DGCR8,EXP5, RAN, DICER, TARBP2, AGO, and PIWI. ProteinsDROSHA and DGCR8 are endonucleases and control theprocessing of the primary microRNA transcript. EXP5 andRAN are involved in translocation of pre-miRNAs from thenucleus to the cytoplasm. DICER endonuclease regulatescleavage of pre-miRNAs to form mature miRNAs and association of mature miRNAs with the RISC. The currentdata on microRNA biogenesis are described in detail in thereview by Smith and Kenny .In the cytoplasm of neuronal cell bodies, miRNAs areoften associated with processing structures that are responsible for storage and degradation of mRNA, and can also befound in stress granules that are formed in response to stress. Expression of miRNAsin neurons is induced by electrical activity and downstreamregulatory cascades at several levels, including the synthesisand processing of the primary transcript, processing of premiRNAs, and assembly of the RISC . However, these processes are still poorly understood.MicroRNAs are highly stable molecules (up to 10 timesmore stable than mRNAs) .The complexity of studying the role of miRNAs in thebrain is determined by the variety of neuronal and glialcells that perform different functions and express differentpatterns of miRNAs . Moreover, each miRNA can have hundreds ofdifferent mRNAs as targets, and expression of a particularmRNA can be regulated by several miRNAs . Therefore, dysregulation of a singlemiRNA can have a large polygenic effect. The number ofidentified miRNAs already amounts to several thousands,and according to various estimates, miRNAs are capable ofregulating the expression of 30 to 70 % of all genes encodingproteins at the posttranscriptional level .It is important that about 70 % of miRNAs are expressed inthe brain, and quite differentially in different regions . In addition, microRNAs can be secreted into the extracellular space, including the circulatorysystem, to ensure intercellular and interorgan communication . The patternof extracellular miRNAs changes in a number of pathologies, and these data are beginning to be used for diagnosticpurposes . Thus,miRNAs are the key regulators of many gene networks and,accordingly, can coordinate the most important processesin the organism. MicroRNAs in learning and long-term memoryCurrently, several learning models are used to study themolecular mechanisms of LTM, which can be divided intoassociative and non-associative ones. The former includesdevelopment of various conditioned reflexes, and the latterincludes non-associative analogs of learning, such as sensitization (facilitation), depression (habituation), post-tetanicpotentiation and post-tetanic depression. Sensitization is \u201cenhancement of a pre-existing responseof an animal to a stimulus as a result of application ofanother, nociceptive (painful) stimulus\u201d. Sensitization isnecessary for an animal to respond to a stimulus that waspreviously insignificant for it . Depression(habituation) is weakening of the response to a previouslysignificant stimulus as a result of its periodic reiteration.Through habituation, an animal learns to ignore stimuli thathave lost their novelty or meaning. At the cellular level,sensitization is associated with an increase in the efficiencyof synaptic communication between neurons, and depression \u2013 with its weakening .Post-tetanic potentiation is improvement in synapse conduction after a series of frequent (tetanizing) stimulationsof incoming fibers. Post-tetanic depression is deteriorationin synaptic conduction after a series of weak rhythmicstimuli.Long-term changes in the efficiency of synaptic transmission in these models require involvement of the genome andare caused by long-term plastic changes in the synapsesthrough remodeling of presynaptic and/or postsynaptic structures, the spiny morphogenesis, and/or growth or eliminationof synapses. Thus, synaptic plasticity is the mechanism by which the brain encodes and stores information. It is believed that these processes underlie LTM formation in bothanimals and humans. The role of microRNAs in synaptic plasticityand local biosynthesis in neuritesThe role of microRNAs in synaptic plasticity has been mostfully investigated using models of long-term post-tetanicdepression (LTD) and post-tetanic potentiation (LTP).Local protein synthesis plays an important role in theseprocesses. It has been shown that the synthesis of receptors,proteins involved in the transport of synaptic vesicles andproteins needed for modeling the growth of spines can occur in neurites, since neurites contain the necessary set fortranslation of mRNA, including ribosomes, and, moreover,pre-microRNA, microRNA and Dicer enzyme, which allowsmicroRNA to regulate local biosynthesis .Thus, during LTD formation in the dendrites of hippocampalneurons, local synthesis of the glutamate receptor GluA1occurs, its expression is regulated by miR-501-3p, and thisprocess is required for remodeling of dendritic spines, thedensity of which determines the efficiency of the synapse.Long-term remodeling of the dendritic tree also involvesmiR-191, miR-135, and miR-137 . On the other hand, miR-26a and miR-384-5pparticipate in the formation of LTP, the expression of whichdecreases during tetanization in an RSK3-dependent manner.Structural and signaling proteins of synapses are the targets of these microRNAs. At the same time,LTP is accompanied by expansion of spines and formationof new ones, while the opposite picture is observed forLTD . It has been suggested that modulation of protein synthesis in synapses may be based on localCa2+-dependent activation of the Dicer enzyme .The effect of microRNA biogenesis disorderson LTM formationIn the initial studies of involvement of miRNAs in learningand memory, animals with genetic impairments of enzymesinvolved in miRNA biogenesis, in particular, with dysfunction of the Dicer, were used . Induced by Tamoxifeninjection, deletion of Dicer in the forebrain of mice (mutation Dicer1CaMKCreERT2) has been shown to cause the loss ofa number of brain-enriched microRNAs, including miR-124,miR-132, miR-137, miR-138, miR-29a/c, and these miceshow improved memory . In animalswith Dicer suppression, the excitability of pyramidal neuronsin the CA1 region of the hippocampus also increased, as wellas induction of \u201cearly genes\u201d required for LTM formation. The above data are supported by thestudies of Hansen et al. and Siegert etal. , which showed that overexpressionof miR-132 in forebrain neurons in adult mice (transgenic mice), and miR-137 in the dentate gyrus leads to LTM impairment.Contradictory to the above are the studies carried out onaging animals in which the content of many microRNAsdecreases with age; however, cognitive impairment occurs. Dicer dysfunction in the cerebellum leads to progressive loss of microRNAand death of Purkinje cells, and in the forebrain it causesabnormal hyper phosphorylation of the tau protein andneurodegeneration similar to that in Alzheimer\u2019s disease,which accordingly impairs cognitive processes . In addition, impairment of microRNA biosynthesis in dopaminergic neuronsdue to suppression or depletion of Dicer (tissue-specificinducible suppression) causes dopaminergic cell dysfunction, while pharmacological stimulation is neuroprotective. In addition, the pharmacologicalinhibition of Dicer activity with poly-lysine (Poly-L-lysinehydrobromide) disrupts formation of a conditioned reflexwith single-trial induced LTM in the mollusk Lymnaeastagnalis and impairs formation of theconditioned defense reflex in the mollusk Helix . Thus, the last two studies show that short-term Dicerdysfunction can lead not to improvement, but to impairmentof LTM.As molecular genetic studies continued, it became clearthat miRNAs are capable of not only inhibiting LTM, butalso improving its formation. Thus, in the lateral amygdala7 microRNAs upregulated and 32 downregulated by auditoryfear training . MicroRNAs miR-9 andmiR-34 do not suppress, but support the capacity of spatiallearning (the Morris water maze) and reference memory,respectively . The expression ofa number of microRNAs in the hippocampus is activatedduring contextual fear formation . Thus, it became clear that the effect ofmicroRNA on cognitive processes can be multidirectional,which was shown in numerous further studies.The best-studied microRNAs whose expression decreasesduring learning include miR-124, miR-134, and miR-206.miR-124 is one of the first studied microRNAs associatedwith LTM formation. It is a highly conserved microRNAwith a high level of expression in the central nervous system. In 2009, a comprehensive work was published, whichfor the first time demonstrated involvement of miR-124 inLTM formation and studied its function . As a learning model, the authors used long-termfacilitation of synaptic connection between sensory andmotor neurons of the mollusk Aplysia. As noted above,facilitation is an essential component in formation of anumber of conditioned reflexes, including defensive ones,and is successfully used in the studies of the mechanismsof LTM formation . It was shown that duringdevelopment of facilitation, the level of miR-124 decreases, and, accordingly, translation of the target of miR-124, thetranscription factor CREB-1, is activated . As a result, CREB-1-dependent induction ofthe genes involved in synaptic modifications takes place,leading to a long-term increase in efficiency of synaptictransmission. At the same time, regulation of miR-124 expression is effected by the modulatory mediator serotonin,which mediates the action of the sensitizing pain stimulus,through PKA-MAPK/ERK-dependent signaling cascadesFurther studies showed that miR-124 also plays an important role in LTM formation in vertebrates, in which,similarly to Aplysia, miR-124 is inhibited during learning. For example, theamount of miR-124 decreases in the hippocampus duringspatial learning and social interactions in mice . In this case, the target of miR-124 is the transcription factor Zif\u200a268, which takes an active part in cognitiveprocesses; accordingly, a decrease in the miR-124 amountinduces translation of Zif\u200a268 . Increasedexpression of miR-124 (vector rAAV1/2-miR-124), orknockdown of Zif\u200a268 (LNA-Zif268 antisense) have a negative effect on LTM, and knockdown of miR-124 (LNAmiR-124 antisense) restores expression Zif268 and reversesof LTM formationThe expression of miR-124 is regulated through cAMPand its intracellular receptors EPAC1 and EPAC2. Moreover, in EPAC\u2013/\u2013 mice, impairment of spatial learningand memory, as well as social interactions, suppression ofsynaptic transmission, and impairment of long-term posttetanic potentiation in the hippocampus are observed . It has been shown that inhibition of miR-124in hippocampal neurons leads to improvement in LTM,potentially through an increase in the level of expressionof genes associated with synaptic plasticity and neuronaltransmission . At the same time,genes associated with translation and neurodegenerativediseases are suppressed.A decrease in the miR-124 expression level associatedwith improvement in LTM formation in mice was noted inthe work of Konopka et al. . miR-124is also involved in memory consolidation during sleep . Post-learning sleep deprivation duringspecific time windows induces expression of miR-124 in thehippocampus, inhibits synthesis of the neurotrophic factorBDNF, which is the target of miR-124, and, accordingly,disrupts LTM consolidation. miR-134 is highly expressed in the brain and is detectednot only in the bodies of neurons, but also in dendrites . As in the case of miR-124, overexpressionof miR-134 in the CA1 regionof the hippocampus leads to significant deterioration inLTM formation in the contextual fear-conditioning paradigmand to abrogated long-term potentiation in this structure. miR-134, like miR-124, affects synapticplasticity through post-transcriptional regulation of CREB-1and BDNF in a CREB-dependent way. In turn, miR-134 expression is regulated by SIRT1 deacetylase. In mutantmice lacking the catalytic activity of SIRT1 in the brain,an increase in levels miR-134 is observed, followed byrepression of target genes, and, accordingly, impairment ofLTM . The increase in miR-134 levels issufficient to mimic the behavioral and electrophysiologicalphenotypes of SIRT1-deficient mice. Conversely, inhibitionof miR-134 reverses memory in SIRT1 knockdown miceand restores long-term potentiation in the CA1 region ofthe hippocampus .Memory impairment under stress is also associated withsuppression of the SIRT1/miR-134 pathway and the downregulation expression of BDNF and synaptic proteins inthe hippocampus . Thus, miR-134 andmiR-124 can have a synergistic effect on the expressionof genes involved in plastic rearrangements. In addition,disruption of miR-134 and miR-124-dependent regulationis an important mechanism underlying cognitive dysfunction in Alzheimer\u2019s disease miR-206. Increased levels of miR-206 are observed in thebrain of Tg2576 mice (a model of Alzheimer\u2019s disease) andin the temporal cortex of the human brain in Alzheimer\u2019sdisease . Decreased miR-206 levels leadto improved memory through induction of the neurotrophicfactor BDNF. Improving memory through decrease in thecontent of miR-206-3p in the hippocampus and cortex isalso facilitated by administration of donepezil, a drug withan antidementional effect .Summarizing the above data, down-regulation expressionof miR-124, miR-134, and miR-206 is necessary for successful formation of LTM, since these microRNAs normallyblock the expression of genes the products of which arenecessary for plastic rearrangements. miR-9-3p positively influences hippocampus-dependentmemory. Inhibition of miR-9-3p in the hippocampus leadsto impairment of long-term post-tetanic potentiation (LTP)and disruption of LTM through increased expression ofDmd (dystrophin) and SAP97 (synapse-associated protein 97) genes, which are negatively correlated with LTP. At the same time, miR-9-5p, which isformed from a common precursor, is not involved in theseprocesses. The miR-9 family is also involved in the regulation of synaptogenesis during early brain development, anda link was found between these developmental events andcognitive functions later in the adult life miR-92. The level of miR-92 increases in the hippocampus during the contextual fear memory formation in mice,which reduces expression of several miR-92 targets, including proteins KCC2, CPEB3 and MEF2D, which negativelyregulates memory-induced structural plasticity . Selective inhibition of miR-92 in CA1 neuronsof the hippocampus leads to upregulation of KCC2, CPEB3 and MEF2D, prevents the learning-induced increase in the spine density and impairsthis type of memory. miR-195. Overexpression of miR-195 in the rat hippocampus using lenti-pre-miR-195 protects against development of dementia, and its inhibition (knockdown by antisense microRNA \u2013 lenti-pre-AMO-miR-195) leads to impairment of spatial memory (Morris water maze) . Potential targets for miR-195 are APP and BACE1proteins associated with \u03b2-amyloid aggregation.MicroRNA cluster miR-183/96/182. Enhanced expression of the microRNA cluster miR-183/96/182 in the hippocampus promotes LTM formation (an object recognitiontask), and miR-183/96/182 expression is regulated by proteinphosphatase PP1 . An increasein the levels of miR-183/96/182 leads to suppression ofhistone deacetylase HDAC9 activity and promotes LTMformation. It is known that HDAC9 negatively affects LTMthrough deacetylation of histones and chromatin remodeling. Downregulation of themiR-183/96/182 cluster leads to memory impairment in theold age, and memory can be improved by overexpression ofthis cluster .Thus, miRNAs , which contribute toLTM formation, repress mRNAs encoding proteins thatinhibit LTP , structural plasticity and gene silencing (histone deacetylaseHDAC9), as well as proteins causing \u03b2-amyloid aggregation (APP and BACE1). Below is a simplified diagram ofmicroRNA-dependent regulation of long-term memoryformation .On the other hand, to date, a large number of miRNAs havebeen described that can influence formation of LT\u041c in bothpositive and negative ways.miR-132. CREB1-dependent activation of miR-132 expression in the hippocampus is observed during formationof fear-induced memory, matches the kinetics of inducingimmediate early genes and regulates the spine size in thepresynapses . While in transgenicmice (tTA::miR132), with increased expression of miR-132in forebrain neurons, violation of LTM formation is observed. It should be noted that in this case,another type of learning was studied \u2013 recognition of newobjects. Nevertheless, the authors note that, in tTA::miR132transgenic mice, there is a decrease in the expression ofMeCP2, a protein involved in development of the Rettsyndrome and other mental disorders, as well as a noticeable increase in dendritic spine density in the hippocampus,which ultimately should lead to improving LTM. The authorsassociate all these inconsistencies with too high expressionof miR-132.miR-34. The data on the effect of the miR-34 family, consisting of three members, miR-34a, miR-34b, and miR-34c, on the learning of microRNAs are even more diverse. It hasbeen shown that inhibition of all the members of miRNAsof this family in hippocampal neurons with using AAVdelivered miRNA sponges reduces the ability for referencememory and causes transcriptome changes associated withtransduction of neuroactive ligand-receptors and cell communication . Inhibition of miR-34aalone has a similar effect on LTM in rats. In this case, weare talking about amygdala-dependent memory (auditoryfear conditioning) . The learning-inducedincrease in miR-34a amount in the basolateral amygdalasuppresses the Notch pathway. Given the leading role ofthe Notch pathway proteins in embryonic developmentand synapse maturation, the authors believe that Notchsignaling normally maintains the steady state of synapticstability by suppressing synaptic plasticity. Fear-mediated,transient increases in miR-34a in the amygdala reduce Notchsignaling, thereby creating an environment that temporarilyallows synaptic modification and hence long-term memoryconsolidationUnlike miR-34a, miR-34c is a negative factor in memoryconsolidation. The level of miR-34c increases in the hippocampus during aging, which contributes to impairmentof learning and memory, can be restored by inhibiting thismicroRNA . In this study, the effectof miR-34c was attributed, at least in part, to a decrease inthe target of miR-34c deacetylase SIRT1. The content ofmiR-34c is also increased in the hippocampus in patientswith Alzheimer\u2019s dementia and in hippocampal neurons inAPPPS1-21 transgenic mice exhibiting \u03b2-amyloid pathologyand cognitive deficits at an early age .In turn, SIRT1 modulates synaptic plasticity and memoryformation through a miR-134-mediated mechanism . Thus, miR-34a is positively associated withamygdala-dependent LTM, while miR-34c is negativelyassociated with hippocampus-dependent LTM.miR-137. This microRNA is being intensively studiedboth in connection with the mechanisms of LTM and withvarious cognitive pathologies, and its functions are verydiverse. It has been shown that activation of miR-137 isrequired for long-term memory formation in the pond snailLymnaea . At the same time, miR-137inhibits the transcription factor CREB2, a negative regulatorof the expression of genes necessary for LTM formation.In mice knocked out of the miR-137 gene, spatial learningand memory are impaired, which is potentially associatedwith increased expression of the Ezh2 gene . Ezh2 encodes histone-lysine N-methyltransferaseinvolved in the methylation of histones at sites that inhibitgene expression. Thus, it has been shown that miRNAsare capable of modulating another regulatory pathway,namely, epigenetic chromatin remodeling. Data obtainedin heterozygous mice with partial loss of miR-137 functionsupport the activating effect of miR-137 on LTM . On the other hand, overexpression of miR-137 inthe dentate gyrus of the hippocampus disrupts presynapticplasticity and impairs fear-induced context memory, whilethe expression of presynaptic target genes associated with therelease of synaptic vesicles decreases . miR-137 is alsoimplicated in the Pb-induced hippocampus-dependent spatial memory impairment . It was shownthat chronic oral administration of lead acetate (PbAc) withdrinking water causes a change in the genomic landscapeof histone H3 methylation at the H3K27me3 site in thehippocampus. It should be noted that the change in methylation is associated with activated interaction of miR-137and EZH2 methyltransferase, which make up a mutuallyinhibitory loop. Overexpression of EZH2 in PbAc-treatedrats reverses H3K27me3 methylation and partially restoresspatial memorymiR-153 also has a multidirectional effect on LTM. Thus,the expression of miR-153 is specifically induced in thehippocampus during fear-dependent memory acquisition. At the same time, miR-153 inhibitsthe expression of key components of the vesicular transportsystem, reduces the level of the glutamate receptor A1 trafficking and neurotransmitter release. On the other hand,knockdown of miR-153 in the hippocampus of adult miceleads to improvement in the fear memory. The authors explain the resulting contradiction by the fact that miR-153,along with, possibly, other fear-induced miRNAs, acts as acomponent of a feedback loop that blocks neuronal hyperactivity by inhibiting the vesicular transport pathway . Dysregulation of miR-153 has beenassociated with decreased learning and memory ability inautistic mice . It has been shown that thetarget of miR-153 is the LEPR (a leptin receptor) and theJAK-STAT signaling pathway regulated by it. Overexpression of miR-153 suppresses LEPR and the JAK-STATsignaling pathway, which leads to an increase in BDNFexpression, an increase in the proliferative capacity of hippocampal neurons, and promotes LTM formation. That is,the high expression of miR-153, and not its knockdown, asstated in the work of Mathew et al. ,improves LTM formation.miR-182. An increase in the expression of this miRNAin the hippocampus within the miR-183/96/182 miRNAcluster promotes the hippocampus-dependent LTM formation . On the contrary, in theamygdala, during formation of amygdala-dependent LTM,a decrease in the amount of miR-182 is noted, and its artificial overexpression leads to a disruption of LTM . The miR-182 targets in the amygdala are the keyactin-regulating proteins, cortactin and Rac1. Interestingly,another member of the miR-183/96/182 cluster, miR-96, isnot expressed in the amygdala. The mechanisms of independent functioning of some microRNAs belonging to clustersare currently not clear, but presumably, this phenomenon isassociated with the type of cells in which their differentialexpression occurs .Thus, miR-132, miR-34, miR-137, miR-153, and miR-182may influence LTM formation in both positive and negativeways, depending on the learning paradigm and the brainstructures involved in learning. In addition, the effect ofmicroRNAs on memory may often depend on their concentration. Thus, a moderate increase in miR-212/132 facilitates,and an excessive increase in its expression negatively affects,learning and memory . The importantrole of miRNAs in LTM formation is also evidenced by therecent studies related to sleep deprivation.It is widely known that even a short period of sleep deprivation may impair memory formation. Sleep disturbance,caused by emotional overload, the rugged rhythm of life andchronic life stress, causes a decrease in performance and cognitive functions in a significant number of the world population. It is believed that one of the mechanisms of the effectof sleep deprivation on cognitive processes may be impairedepigenetic regulation of gene expression, including genesassociated with microRNA dysfunction .Thus, the recent studies have shown that sleep deprivationsignificantly changes the profiles of DNA methylation and,accordingly, the synthesis of RNA, including microRNA. On the other hand, miRNAs areinvolved in the regulation of circadian rhythms that regulate the sleep and wakefulness cycles .Disruption of microRNA biogenesis may lead to changes inthe circadian rhythms and potentially affect cognitive abilities. In patients with depression and late insomnia, geneticvariants of miR-182 miRNA were found that induce inhibition of expression of circadian clock proteins CLOCK andDSIP . In addition, impaired expressionof miR-182, along with miR-132 and miR-124, is observedduring the paradoxical sleep phase deprivation and leadsto disruption of hippocampus-dependent LTM . At the same time, the synthesis of the growthfactor BDNF, which is involved in memory consolidationduring sleep, changes markedly . Therelation of these microRNAs with numerous cognitive processes has been described in the chapters above. In addition,miR-132 is a key pathway for coupling the circadian rhythmand the rhythm of cognitive abilities .Sleep deprivation also disrupts the content of miRNAslet-7b, miR-125a, and miR-138 . It isbelieved that induction of the epigenetic processes causedby sleep deprivation is carried out by signaling cascades thatregulate synaptic plasticity . Sleepdisturbance is common in people with fear-related anxietydisorders. It has been shown that some microRNAs, suchas miR-132 and miR-144-3p, play an important role bothin generation of fear and in suppression of memories of itand are associated with consolidation and reconsolidation ofLTM, respectively . At the sametime, impaired miR-132 expression is observed during sleepdeprivation and is accompanied by cognitive dysfunctions.In recent years, more and more data have been accumulatedthat microRNAs play an important role in cognitive disorders in neurological, neurodegenerative, and age-relateddysfunctions . Coverage of these issues requiresa separate review. However, it is important to note that thereis an increasing number of predictions regarding the possibility of therapeutic treatment of a number of cognitiveimpairments by influencing microRNA biogenesis . Optimismin this area is determined by the emergence of new genomeediting technologies using the CRISPR/Cas9 system adaptedto microRNA . In addition, CRISPRCas9 systems have been developed, which allows editing ofthe genome in a specific cell population without affectingother organs and tissues . These technologies are especially importantin studying the mechanisms of the central nervous systemfunctioning and the prospects for therapeutic interventionin the pathogenesis of brain diseases.On the other hand, it has been known for a long time thatcognitive processes can be improved through intensificationof cognitive processes, fine motor movement work or physical exercise. In recent years, it has been shown that mentaland physical activities improve the epigenetic processes involved in formation of LTM and protect neurons from death.For example, running exercise helps to improve memoryin mice with traumatic brain injury . Atthe same time, there is a decrease in the content of miR-21and an increase in the number of branch points of the hippocampal neurons. Physical exercise also improves thecognitive function in aged mice . The process involves miR-137, which is associatedwith good memory and neurogenesis in adults (the rate ofneurogenesis decreases with age). In addition, the possibilityof improving aging-related memory decline by enriching theenvironment has been shown . In thiscase, an increase in the biogenesis of the miR-183/96/182cluster is stimulated, which is closely associated with hippocampus-dependent memory. Environmental enrichmentalso attenuates mild cognitive impairment by activating theSIRT1/miR-134 signaling pathway in the hippocampus, followed by ultrastructure changes of synapses and dendriticremodeling . Moreover, it has been shownthat an environmental enrichment is capable of enhancingsynaptic plasticity and cognition even in the next generation,with sperm RNA, and especially miRs 212/132, mediatingthe effect . Widely available ways toimprove cognitive abilities are shown in Fig. 2.Mental work, physical exercise, manual creativity, lightstress, good sleep and a good mood are able to protectneurons from death and improve cognitive processes viaepigenetic mechanisms on chromatin remodeling andmiRNA expression.Thus, miRNAs are widely involved in the regulation of geneexpression required for the long-term memory formation.Further study of ways to regulate microRNA activity in individual cell populations, as well as detailed study of theirtargets using bioinformatics analysis methods, will help tobetter understand the molecular genetic basis of long-termmemory and potentially to develop methods of treatment incase of cognitive dysfunctions in neurodegenerative pathologies and senile dementiaThe authors declare no conflict of interest.Ai J., Sun L.H., Che H., Zhang R., Zhang T.Z., Wu W.C., Su X.L.,Chen X., Yang G., Li K., Wang N., Ban T., Bao Y.N., Guo F.,Niu H.F., Zhu Y.L., Zhu X.Y., Zhao S.G., Yang B.F. 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Neuron. 2012;73(4):774-788. DOI 10.1016/j.neuron.2012.02.003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307595.You Y.H., Qin Z.Q., Zhang H.L., Yuan Z.H., Yu X. MicroRNA-153promotes brain-derived neurotrophic factor and hippocampalneuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR. Biosci. Rep. 2019;39(6):BSR20181904. DOI 10.1042/BSR20181904. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591574.Zovoilis A., Agbemenyah H.Y., Agis-Balboa R.C., Stilling R.M.,Edbauer D., Rao P., Farinelli L., Delalle I., Schmitt A., Falkai P.,Bahari-Javan S., Burkhardt S., Sananbenesi F., Fischer A. MicroRNA-34c is a novel target to treat dementias. EMBO J. 2011;30:4299-4308. DOI 10.1038/emboj.2011.327. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199394."} +{"text": "Plagiotheciumneglectum, P.neglectum, currently known from the original M\u00f6nkemeyer collections, was found in the Herbarium B (B 30 0105646). The features given in the diagnosis of this taxon are consistent with those of the lectotype of Stereodonnemoralis Mitt.; only the leaf apex from Figure 207c was designated.In the protologue of ure 207c is diffe Plagiotheciumneglectum M\u00f6nk. was described by M\u00f6nkemeyer in Die Laubmoose Europas (P.sylvaticumauct. non (Brid.) Bruch & Schimp. A.Jaeger), wherein the author also retains and uses the name P.silvaticum (P.sylvaticumnom. illeg. orthogr. pro (Brid.) Bruch & Schimp.) which is now understood as P.denticulatumvar.obtusifolium (Turner) Moore ( Europas . The namr) Moore .P.silvaticum and P.succulentum (Wilson) Lindb., also describing that the cell areolation in P.neglectum is as wide as that of the former, and the appearance of the turf and the leaves and habitat are similar to the latter.In the diagnosis, P.neglectum was treated as a separate species (P.silvaticum (P.sylvaticum) (P.silvaticumvar.neglectum (M\u00f6nk.) F.Koppe Schimp. This researcher also suggested that the plants previously named P.sylvaticum and P.neglectum should instead be assigned the earlier available epithet, P.nemorale (Mitt.) A.Jaeger.For decades, species , as a syvaticum) , or a va F.Koppe . IwatsukP.neglectum with P.silvaticum (P.sylvaticum), did not analyze the original materials of this taxon. Also, while P.neglectum, his proposed synonymization of this taxon with P.nemorale has nevertheless been widely accepted found some of his herbarium specimens to be stored in the B, H, M and MANCH herbaria.Before starting the research, efforts were made to find all herbaria in which W. M\u00f6nkemeyer collections are deposited. P.neglectum, contact was made with the staff of all the above-mentioned institutions. All curators indicated that the original materials of the analyzed taxon had been deposited at the Herbarium HBG. This was also confirmed in a paper by Walter and Martienssen (1976) describing the bryological collection of this herbarium.To find the original materials of P.neglectum . However, like the other ones, this is also not mentioned in the protologue appears correct.The characteristics given in the diagnosis and figures are consistent with those of the ectotype . Only thShenzhen Code , collected by M\u00f6nkemeyer and signed by him as \u201cP.neglectum\u201d. The plants of specimen B 30 0105646 also show a serrate leaf apex should be designated as the epitype; it is the original material catalog.This is an excellent choice because this specimen comes from the original M\u00f6nkemeyer collection; this way, it is practically impossible to change the understanding of the name Stereodonnemoralis Mitt., J. Linn. Soc. Bot. Suppl. 1: 104 (1859) \u2261 Plagiotheciumnemorale (Mitt.) A.Jaeger, Ber. St. Gall. Naturw. Ges. 1876\u20131877: 451 (1878) \u2261 P.silvaticumvar.nemorale (Mitt.) Paris, Index Bryol.: 967 (1898). Type citation: Hab. In Himalayae orient. reg. temp., Sikkim, in monte Tonglo (ad radicem filicis cujus dam), J. D. Hooker ! Lectotype: \u201cHerb. Ind Or Hook. Fil. & Thomson Stereodonnemorale m. Hab. Sikkim, Tonglo Regio temp. Alt. \u2013 J. D. H.\u201d \u2013 BM 1030713!: isolectotype: NY 913349! = P.neglectum M\u00f6nk., Laubmoose Europas 866 (1927). Lectotype (designated here): Figure 207c without a part of the figure with the top of the leaf (Epitype (designated here): Wesergebirge: in Erlenbr\u00fcchen bei Eschershausen, Juli 1900, M\u00f6nkemeyer s.n., B 30 0105646 ; Wesergebirge: Bodenwerder, K\u00f6nigszinne, Juli 1901 (W. M\u00f6nkemeyer s.n.); Hessen, Rh\u00f6n: Gr. Nallen, Juli 1906 (W. M\u00f6nkemeyer s.n.). Vogtland: Plauen, Triebtal, 25.07.1904 (E. Stolle s.n.); Bayern: Allg\u00e4u, Hinterstein, Sauwald, Aug. 1906, u. Regensburg, U-Lichtenwald, Schindelmacherh\u00e4nge, Nov. 1906 (I. Familler s.n.); Prien/Chiemsee: 500 m, Juni 1911 (T. Linder s.n.); M\u00e4hren: Oppafall, Juli 1904 (J. Podp\u011bra s.n.); Ostpreu\u03b2en: Labiau, Juli 1864 (H. v. Klinggr\u00e4ff s.n.); Kurland: Usmaitensee, Moritzholm, Mengwald, 3.8.1913 (K. R. Kupffer s.n.); sine loc. et dat. (W\u00fcstnei s.n. 380).The remaining original material according to Walter and Martienssen (1976) was confirmed to have been lost at HBG: Th\u00fcringen: Eisenach, Annatal, 26.7.1898, u. Wartburg, 2.5.1915 ("} +{"text": "Kohleria (Gesneriaceae) in Ecuador and Colombia. A change in the rank from a variety to species is recognized for Kohleriaanisophylla (Fritsch) Wiehler. The combination Kohleriaandina (Fritsch) J.L. Clark & Jost, comb. nov. is provided here and a lectotype is designated. The updated circumscriptions of these two species are supported by morphology and geographic distribution. The presence of an epiphytic habit for Kohleria is discussed. Field images based on recent expeditions are provided to support the circumscriptions presented here.Recent studies of type specimens and exploratory research expeditions in the northern Andes have resulted in an updated circumscription and recognition for two species of Gesneriaceae, with over 3400 species and 150+ genera Regelvar.hirsuta J.L. Clark & Jostcomb. nov.C651D84D-AF43-5148-AE25-6A5A8DA0BB0Furn:lsid:ipni.org:names:77218228-1CapaneaandinaR. Spruce 5178 . Fritsch, Bot. Jahrb. Syst. 50: 431\u2013432. 1913 (\u201c1914\u201d). Type: Ecuador. Andes Quitenses, Tunguragua, 1857, Kohleria was a terrestrial habit. In the generic delimitation of Kohleria in the Tungurahua province of Ecuador. In contrast, Kohleriaaffinis is widespread in the northern Andes of Colombia , Ecuador , and northern Peru (Amazonas and Cajamarca). The authors\u2019 field work from the upper slopes of Tungurahua, an active volcano in the western Andean slopes of the Cordillera Oriental, revealed little overlap. Kohleriaandina is locally endemic to elevations above 2500 meters and K.affinis is widespread and located in forests below 2500 meters. Intermediate forms were not found here, indicating that these two forms are geographically separated by elevation and supported as different biological species.F.C. Lehmann 4869 (F0060498) from Colombia and R. Spruce 5178 from K (K000395097) from Tungurahua, Ecuador. The specimen of F.C. Lehmann 4869 (F) is more similar to the widespread Kohleriaaffinis. The specimen of R. Spruce 5178 from (K) is similar to the locally endemic Kohleriaandina, and is designated as the lectotype to stabilize this species concept. According to K.affinis is the presence of dark red trichomes on the peduncles and pedicels. In contrast, the peduncle and pedicel trichomes on F.C. Lehmann 4869 are transparent and more similar to K.affinis.Syntypes are from two distinct localities: Taxon classificationPlantaeLamialesGesneriaceae(Fritsch) WiehlerD3BAC67D-CB74-5A49-AA88-BB9A52AE8F15Kohleriaanisophylla (Fritsch) Wiehler.KohleriaanisophyllaDiastemaanisophyllum Fritsch. (Fritsch) Wiehler, Selbyana 5: 62. 1978. Type: Based on Kohleriavillosavar.anisophyllaDiastemaanisophyllum Fritsch. Basionym. (Fritsch) Kvist & Skog, Smithsonian Contr. Bot. 79: 70. 1992. Type: Based on DiastemaanisophyllumF.C. Lehmann 5843 . Type: Colombia. [Nari\u00f1o] Piedra Ancha, West of Andes of Tuquerres, NematanthuserianthusHartweg s.n. (holotype K000509985). Bentham, Pl. Hartw: 231. 1846. Type: Ecuador. Pichincha: Quito towards Nanegal, ColumneaerianthaNematanthuserianthus Fritsch. (Bentham) Hanstein, Linnaea 34: 391. 1865. Type: Based on DiastemaanisophyllumFritschvar.quitenseW. Jameson s.n. (holotype W). Fritsch. Bot. Jahrb. Syst. 50(4): 408. 1913 (\u201c1914\u201d). Type: Ecuador. [Pichincha] Quito, Kohleriaanisophylla . Kohleriaanisophylla and recognized it at the rank of species. Kohleriavillosavar.anisophylla. Based on limited material, F.C. Lehmann 5843) and a recently collected specimen from Ecuador (C. Luer & A. Hirtz 2672). K.anisophylla, K.villosa, and K.hypertrichosa Roalson and Boggan represented an autapomorphic synapomorphy of epiphytism in traditionally recognized Kohleria. What is noteworthy about Kohleriaanisophylla and K.hypertrichosa is their previously unreported epiphytic habits. Thus, the presence of an epiphytic habit in K.anisophylla and K.hypertrichosa could represent an additional independent origin of epiphytism in Kohleria. Several populations of Kohleriaanisophylla were observed and documented with dorsiventral shoots, a feature that is common in facultative epiphytes in other Gesneriaceae genera. Many members of Columnea have strongly anisophyllous leaves \u2013 especially species that are facultative epiphytes with dorsiventral shoots. Other species of Gesneriaceae that are facultative epiphytes with dorsiventral shoots include Cremospermaanisophylla J.L. Clark & L.E. Skog, Drymoniaanisophylla L.E. Skog & L.P. Kvist, and the majority of species in Monopyle Moritz ex Benth. and Trichodrymonia Oerst. Likewise, Kohleriaanisophylla and K.hypertrichosa are facultative epiphytes with dorsiventral shoots and anisophyllous leaves. In contrast, Kohleriavillosa is a terrestrial herb with isophyllous leaves in the movie Star Wars.The corollas of ous Figs , 4. The ose Fig. . The speKohleriavillosa and K.anisophylla are easily recognized when sterile. The opposite leaves of Kohleriaanisophylla are consistently unequal in size or anisophyllous (Fig. Kohleriavillosa are consistently equal in size or isophyllous (Fig. K.anisophylla from the erect shoots of K.villosus.ous Fig. . In contous Fig. . In addi"} +{"text": "NAR Cancer, Volume 3, Issue 2, June 2021, zcab021, https://doi.org/10.1093/narcan/zcab021The Authors wish to add a new source of Funding:NIH ; Cybrexa Therapeutics. The work was partially supported by NIH/NIGMS [R01 GM073857] to O.A.A., Y.K.R. and D.M.E. Funding for open access charge: National Institutes of Health .The published article has been updated."} +{"text": "P < 0.001, respectively) and associated with an enhanced risk of venous and arterial thrombosis. The increase of circulating LPS may have different explanation, but enhanced gut permeability is likely to play a major role. Thus, patients with COVID-19 displayed a significant correlation between serum LPS and zonulin, an indirect marker of gut permeability (We thank Drs Chen and Vitetta for the interesting comment to our study regarding the detection of low-grade endotoxemia in patients with coronavirus disease-19 (COVID-19) . We founeability . As outleability and witheability . It seemeability . HoweverGuarantor of the article: Francesco Violi, MD.Specific author contributions: F.V. conceptualized and wrote the draft. P.P., A.O., and V.C. revised and edited the article.Financial support: None to report.Potential competing interests: None to report."} +{"text": "Plant sugar transporters play an essential role in the organism\u2019s productivity by carrying out carbohydrate transportation from source cells in the leaves to sink cells in the cortex. In addition, they aid in the regulation of a substantial part of the exchange of nutrients with microorganisms in the rhizosphere (bacteria and fungi), an ty essential to the formation of symbiotic relationships. This review pays special attention to carbohydrate nutritionduring the development of arbuscular mycorrhiza (AM), a symbiosis of plants with fungi from the Glomeromycotinasubdivision. This relationship results in the host plant receiving micronutrients from the mycosymbiont, mainlyphosphorus, and the fungus receiving carbon assimilation products in return. While the eff icient nutrient transportpathways in AM symbiosis are yet to be discovered, SWEET sugar transporters are one of the three key families ofplant carbohydrate transporters. Specif ic AM symbiosis transporters can be identif ied among the SWEET proteins.The survey provides data on the study history, structure and localization, phylogeny and functions of the SWEETproteins. A high variability of both the SWEET proteins themselves and their functions is noted along with the factthat the same proteins may perform different functions in different plants. A special role is given to the SWEET transportersin AM development. SWEET transporters can also play a key role in abiotic stress tolerance, thus allowingplants to adapt to adverse environmental conditions. The development of knowledge about symbiotic systems willcontribute to the creation of microbial preparations for use in agriculture in the Russian Federation. Sugar transporters in plants are customarily divided into threemajor classes: SUT (SUC), MST , and SWEET. The mostwell studied transporters are SUT and MST. SUT carry outlong-distance transportation of sucrose from plant leaves tothe targeted plant organs and tissues. They then disintegrateinto monosaccharides and are subsequently transported byMST proteins. The major part of the transporters from SUTand MST classes are known to be non-specific to symbioticplant-microbial systems such as arbuscular mycorrhiza (AM).However, in 2010, Li-Qing Chen described a new transporterclass SWEET. SWEET transporters carry out non-volatilebidirectional transportation of sugars in all plant organs andtissues. At present, the SWEET protein family is the leaststudied group of transporters. According to current knowledge,proteins specific to AM symbiosis may be detected inside theSWEET transporter group . Various sourcesin the literature provide conflicting information concerning theSWEET protein class. This survey is an attempt to tackle theissue and combine knowledge about the proteins of the group.Thus, the aim of the current research is to provide an overviewof the data on gene phylogenesis inside the SWEET class andfunctions of the proteins encoded with the aforementionedgenes as well as to assess their role in the sugar transportationprocess during the formation of AM symbiosisSWEET proteins, identified in the late 1990s, were first calledMtN3 (involved in the development of Medicago truncatulaGaertn. nodules) and Saliva . Thatis why the transmembrane domains made of those proteinswere named \u201cMtN3/Saliva\u201d, or \u201cMtN3_slv domain\u201d and arealso known as \u201cPQ loop\u201d . In 2010, Li-Qing Chen was the first to isolate SWEET transporters intoa separate family of proteins by providing a detailed descriptionof those pertaining to Arabidopsis thaliana (L.) Heynh.Seventeen different transporters were discovered, described,and named according to the species belonging to a particularplant and the protein number (e. g. AtSWEET17). The same paper provides a detailed description of the SWEET proteinsin Oryza sativa L. . Afterwards SWEETproteins were found in a number of other plant species andalso in animals and prokaryotes (the latter were namedSemiSWEET). Now all living organisms are generally considered topossess SWEET or SemiSWEET proteins .Newly found SWEETs are numbered according to orthologywith Arabidopsis proteins. However, some discrepanciesand variations in A. thaliana numbering have beennoted 1 .SWEET proteins are uniporters, transporting carbohydratesacross membranes along a concentration gradient, typically localizedon the plasma membrane . SWEETproteins in plants usually contain seven transmembrane (TM)helices . Nevertheless, in 2015, G. Patil etal. discovered that Vitis vinifera L. SWEET is made of fourteenTMH (transmembrane helices), which proves that theSWEET protein helix structure may vary .Bacterial SemiSWEETs are the smallest among the knowntransporters. Consisting of about one hundred amino acidscoiled in three spirals, i. e., three TMHs, they form a triple helixbundle (THB). The duplication of THB in prokaryotes leads tothe emergence of eukaryotic SWEET transporters consistingof two THBs and an additional linker helix, numbered TMH4. Moreover, it is noteworthy that the threeTMHs in THB are not arranged in series on the membrane.The third TMH is squeezed between the first and the secondone. There, the N-terminus of the protein is found on theouter side of the membrane, while the C-terminus is locatedon the inner side. In eukaryotes, the C-terminus is elongatedand contains phosphorylation sites that can be used for posttranslationalmodification . The nucleotidesequence, encoding TMH4, is known to be the most variableof TMHs, and its origin is currently being debated .http://vavilov.elpub.ru/jour/manager/files/Suppl_Kryukov_EnglSupplementary Materials are available in the online version of the paper:Interestingly, some eukaryotes exhibit SWEET proteinstructures similar to the prokaryotic ones. For instance, wheatTriticum aestivum L. may also have a SemiSWEET consistingof three and four TMHs . Accordingto researchers, the presence of TaSWEET with 3, 4, 6, and7 TMHs in wheat implies that both duplication and fusion ofSWEET protein structures can occur in the genome . SuperSWEET sugar transporters found in Phytophthoracontain from 18 to 25 TMHs and are composedof 5\u20138 semiSWEET loops . Thus, the structuresof SWEET proteins should be assumed to be highlyvariable.In the construction of a phylogenetic tree, it was revealedthat the SWEET genes of plants are still grouped into fourclades, despite their low homology . Thisevolutionary division occurred long ago, and representativesof each of the clades are observed in almost all terrestrial plants. With all this, the second clade is the mostancient, and its representatives share certain homology withthe SWEET proteins in algae . In mammalsand some microorganisms (e. g. Chlamydomonas), proteinshave been found to fall into clade V, separate from the otherSWEETs .The increasing number of SWEET isoforms is a consequenceof duplication or fusion of the THB genes. Thiscontributes to the expansion of transporter functions andplant adaptation under new conditions .The number of SWEET isoforms varies significantly amongplant species. For example, unicellular and green algae have1 to 3 SWEET isoforms, while monocots are observed topossess from 18 to 23, and dicots from 15 up to 68 . According to other data, T. aestivum wheat (monocotyledonous)is known to have 108 isoforms of SWEETgenes localized on 21 chromosomes, while some of themare orthologs of the SWEETs of Arabidopsis (of 14 genes ofArabidopsis), and some belong to three new types that do nothave significant homology with Arabidopsis genes . M. truncatula has up to 26 isoforms . At the same time, it is likely that these are not allof the identified transporters, since, by 2015, only 24 of themwere isolated .The representatives of the four clades are considered to bedivided not only phylogenetically, but also functionally. Thus,most researchers argue that (1) the protein representatives ofclades I and II transport hexoses, (2) proteins of clade III aremainly involved in the transport of sucrose, and (3) those ofclade IV are principally involved in the transport of fructose .But this is not necessarily so. In 2019, B. Hu et al. showedthat MtSWEET5b and MtSWEET7 (M. truncatula) are ableto transport not only hexoses, but also sucrose. Other plantsmay also be exceptions, for instance LjSWEET3 (Lotusjaponicus L.) also transports sucrose instead of hexoses.MtSWEET16 may be involved in the transportation processof sucrose and mannose. It is therefore impossible to speakstrictly about the clade division of the SWEET genes for the types of the transferred substrate .The nucleotide sequence analysis of the SWEET genesshows their significant variability. Between the four clades,it can reach up to 80 % . With such variability, it is typically impossibleto align sequences and then build phylogeny. In this regard,the existing phylogenetic trees of the SWEET genes should betreated with extreme caution. The intron-exon structure of theSWEET genes may also vary notably . Mostof the MtSWEET genes (in M. truncatula) contain 5 introns,excluding the genes MtSWEET4, MtSWEET6, MtSWEET7and MtSWEET13 which include 4 introns, and MtSWEET2bwhich contains 16 introns . The structureof the M. truncatula SWEET proteins is also heterogeneous:most contain 7 TMHs, but MtSWEET4 and MtSWEET11have 6 TMHs, and MtSWEET2b contains 15 TMHs insteadof 7 .As has already been mentioned, the representatives of thefour clades can be divided in accordance with their functions.However, it should be noted that different authors providevaried data on functions of the certain SWEET proteins . This may be due to several possiblereasons: (1) orthologs of the SWEETs can perform differentfunctions in different species; (2) orthologs can perform differentfunctions under different conditions and their genesare expressed in different ways; (3) possible paralogs withineach clade may be similar and hence may be misidentified.In all cases, SWEET proteins are non-volatile bidirectionaluniporters. However, according to some researchers, the factthat all SWEET transporters are uniporters has not beencompletely proven . SWEET proteins areinvolved in a variety of processes, whether in plants or mammals. In addition to the transportationof carbohydrates, they are most likely to participate inthe transport of other agents such as gibberellins, which isthe case of Arabidopsis . In peas (Pisumsativum L.), it was also discovered that the interaction betweenthe SWEET transporters and CWINV inthe presence of cytokinins leads to the formation of multipleshoots and the loss of apical dominance during infection withthe pathogen Rhodococcus fastian .SWEET transporters can also play a role in abiotic stresstolerance, allowing plants to adapt to adverse environmentalconditions .Various authors have associated the accumulation of sugarsin plants with abiotic stresses . Low temperatures,water, and other stressful environmental factors areable to induce the expression of the SWEET genes in plants,which leads to the assumption that these genes are associatedwith plant responses to these stresses .There is a great deal of literary data on the functions of theSWEET proteins in plants of various species. For example,LjSWEET3 mediates the transportation of sucrose to nodules. The AtSWEET1 and AtSWEET5 genesare significantly expressed at different stages of pollen maturation.Almost all representatives of clade II are involved in thetransportation of sugars to the reproductive organs, i. e., pollen,seeds, and some to fungal pathogens .Genes AtSWEET11 and AtSWEET12 have been established asimportant transporters of sucrose from parenchyma cells tophloem . At the same time, SWEET proteinsof the clade III are associated with susceptibility and resistanceto pathogens . According to W.J. Guoet al., proteins of the clade IV \u2013 AtSWEET17, AtSWEET16 \u2013are active in root cortical cells and are localized on the tonoplast.Rhizosphere pathogens can cause an increased expressionof clade III proteins, which leads to additional transport ofsucrose to the roots and contributes to the nutrition of rhizospheremicroorganisms . In 2010, itwas shown by L.-Q. Chen et al. that pathogenic bacteria, forexample Xanthomonas, are able to enter tissues of the hostplant and induce the expression of SWEET genes to obtain sugars.Like symbiotic AM fungi, pathogenic fungi also have theability to induce the expression of genes in order to get sugarfor themselves .The expression of a significant number of alterations inSWEET under the influence of stress factors such as waterdeficiency leads to a notably increased expressionof theMtSWEET3a,MtSWEET3b, MtSWEET9band MtSWEET13genes, while the expression of MtSWEET1a, MtSWEET3c,MtSWEET15cdrops significantly. According to J. Doidy et al., MtSWEET16is unique in that its expression is mainly enhanced in leaves,whereas the pea ortholog PsSWEET16 is expressed primarilyin the roots and stem . SWEET3 orthologsPsSWEET3.1, MtSWEET3.3 and LjSWEET3 , SWEET11 orthologs MtSWEET11and PsSWEET11 and SWEET15 orthologsMtSWEET15.3and PsSWEET15.3 arespecifically expressed in root nodules in leguminous plants.J. Manck-G\u00f6tzenberger and N. Requena note that numeroustransporters show significantexpression in AM symbiosiswhile being non-specific to it . In turn, A. Kafle pointed out that SWEET1 orthologs(MtSWEET1.2 and PsSWEET1.2) can be expressed in bothmycorrhized roots and root nodules .As is known, according to the data of the transcription profiles,not all transportersof the SWEET family have yet beenfound, nor have all known transporters of this group beenlocalized in a plant cell and their exact function established. Only now is the localization of mostSWEET sugar transporters receiving proper attention as such study requires a separateexamination of each individual transporter for each individualplant species. Their functions and localization also require confirmation.On the other hand, the question of the participation of SWEET proteins in the specific transport of sugars fromthe host plant to mycosymbiont AM fungi is quite urgent andrequires detailed research, since knowledge of the mechanismsof active carbohydrate nutrition of a mycosymbiont will allowus to understand the mechanisms that lead to the formationand development of effective interaction between partners inAM symbiosis.According to the literary data, it should be assumed thatmost of the SWEET transporters of the clades I, II, III arelocalized in the plasma membrane . The figurerepresents a root cell of a host plant with an arbuscule \u2013 between the periarbuscular membrane (PAM)and the arbuscular membrane (ArM) with the arbuscular cellwall (ACW), formed in place of the cell wall of the host plant).The peculiarity of transport processes under AM conditionsis analyzed by comparing cells with and without arbuscules. Thus, J. Manck-G\u00f6tzenberger andN. Requena were thefirst to show that the main transport of sugars in Solanumtuberosum from the host plant to the AM fungus Rhizophagusirregularis can occur due to the facilitators of sucrose andglucose \u2013 StSWEET12 and StSWEET7a, respectively . StSWEET12 and StSWEET7a operate on PAMand transport sugars from the cytoplasm to the PAS and viceversa. From here, glucose is transported through the ArM fromPAS in the arbuscule using the fungal monosugar transporterRiMST2 ), or as a result of GpMST1 functioning(Geosiphonomyces pyriformis Cif. & Tomas) . The sucrose transportation through the ArM may occurvia the fungal sucrose transporter RiSUC1 . Subsequently, sugar is transported along the intraradicalmycelium as glycogen into the extraradical mycelium ofthe AM fungus . On the other hand, thecytoplasm sugar in the cells of the root cortex can be regulatedby their transfer from the vacuole by tonoplastic transporters,which include the glucose facilitator StSWEET2c .The sugar transportation apoplastic pathway is carried outto cells both with and without AM fungus via SWEET hexosetransporters . It is assumed that there may be specific SWEET facilitatorsfor AM symbiosis. For example, StSWEET12 andStSWEET7a proteins may carry out specific transportation ofsucrose and glucose in S. tuberosum through the plasmalemmaof root cortex cells containing arbuscules . Once there,the effectors secreted by AM fungi either directly activate theexpression of the SWEET genes, or indirectly through theactivation of transcription factors . The LjSWEET3 protein, which is responsiblefor the transportation of sucrose to the cells with arbuscules in Lotus japonicus, is claimed to be a specific facilitator as well . Proteins AtSWEET15 and MtSWEET11 are known to be non-AM-specific SWEET transporters, localizedon the root cell plasma membrane .The discussion of the SWEET protein localization on the organelles of theroot cell is controversial. Thus, according to some data, transporters of theclade IV (AtSWEET16 and AtSWEET17) can be localized in the tonoplastof the plant vacuole . On the other hand, clade III sucrose transportersAtSWEET9 and AtSWEET15 may be localized on the membrane of the trans-Golgi network .Thus, summarizing the information on the localization of the SWEET transportersin AM, it can be concluded that none of the transporters has shownspecific localization simultaneously in two or more plant species. Nor is thereattested specific gene expression under the same conditions, as, for example,in the phosphate transporter (PT4) of M. truncatula and in a number of otherplant species. The first to be verified are StSWEET12 and StSWEET7a.The transporter functions in AM maybe assumed on the basis of general informationabout the clades of proteins of theSWEET family, but it should be noted thatthere have been no detailed studies of boththe localization and functions of these proteinsin AM symbiosis yet. There are onlyassumptions about their role in AM. Forinstance, in a recent work by J. An et al.(2019), it has been noted that MtSWEET1bmay supply AM glucose to fungi. Accordingto the M. truncatula gene expressionatlas ,MtSWEET1b and MtSWEET6 are highlyexpressed in arbuscular cells, and their putativeorthologs StSWEET1a, StSWEET1b,and StSWEET7a (S. tuberosum L.) alsodemonstrate high transcription levels inmycorrhizal roots . SWEET transporters ofclade I are those most likely to participatein the supply of sugars to symbiotic systems,including AM . Basedon this information, it should be assumedthat studies of the function of the SWEETproteins are still very fragmentary . The confirmation in severalplant species remains an urgent task.SWEET proteins are essential for the transportationof carbohydrates in plants. Proteinsspecific to the various forms of symbiosiscan be found amongst the SWEET class.Primarily, they can be located in clades Iand III. SWEET transporters are quite variable,a change in external conditions maylead to the emergence of numerous isoformswith varying functions. Hence, SWEETprotein identification and selection of primersfor the gene amplification requiresprudence. Close paralogs may be very similar;however, high variability betweenclades does not allow for the constructionof a reliable phylogenetic tree with all theensuing consequences. This high variabilitymay account for the scatter of the datarelated to SWEET protein functions . Still, a hypothesis aboutthe universality of the range of SWEETgenes may be put forward, mainly in caseof similar gene structure. Furthermore, thereare reasons to believe that not all of thegenes from the SWEET class have yet beenidentified for M. truncatula. All this testifiesin favor of the fact that the understanding ofthe functions of these transporters will beexpanded in the coming years.The authors declare no conflict of interest.Ait Lahmidi N., Courty P.E., Brul\u00e9 D., Chatagnier O., Arnould C., DoidyJ., Berta G., Lingua G., Wipf D., Bonneau L. Sugar exchanges inarbuscular mycorrhiza: RiMST5 and RiMST6, two novel Rhizophagusirregularis monosaccharide transporters, are involved in bothsugar uptake from the soil and from the plant partner. Plant Physiol.Biochem. 2016;107:354-363. DOI 10.1016/j.plaphy.2016.06.023An J., Zeng T., Ji C., de Graaf S., Zheng Z., Xiao T.T., Deng X., Xiao S.,Bisseling T., Limpens E., Pan Z. A Medicago truncatula SWEETtransporter implicated in arbuscule maintenance during arbuscularmycorrhizal symbiosis. New Phytologist. 2019;224:396-408. 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DOI 10.3390/ijms19010302"} +{"text": "Nature Communications 10.1038/s41467-021-27219-2, published online 29 November 2021.Correction to: Priv. Laws Int. Bus. Rep.1, 3\u20135 (2021).\u2019 The correct reference is \u20181. Greenleaf, G. Global Data Privacy Laws 2021: Despite COVID Delays, 145 Laws Show GDPR Dominance. Priv. Laws Int. Bus. Rep.1, 3\u20135 (2021).\u2019The original version of this Article listed the wrong reference in the first position in the Reference list. The original reference in the first position read as \u20181. Greenleaf, G. Jamaica adopts a post-GDPR Data Privacy Law. This has been corrected in both the PDF and HTML version of the Article."} +{"text": "There was an production error in the reference details for Palmiero et al., 10.3389/fpsyg.2019.01274,\u201d it should be \u201cPalmiero, M., Giulianella, L., Guariglia, P., Boccia, M., D'Amico, S., and Piccardi, L. (2019). The dancers' visuospatial body map explains their enhanced divergence in the production of motor forms: evidence in the early development. Front. Psychol. 10:768. doi: 10.3389/fpsyg.2019.00768\u201d.Instead of \u201cPalmiero, M., Giulianella, L., Guariglia, P., Boccia, M., D'Amico, S., and Piccardi, L. (2019). The dancers' visuo-spatial body map explains their enhanced divergence in the production of motor forms: evidence in the early development. Front. Psychol. 10:768. doi: The publisher apologizes for this mistake. The original version of this article has been updated."} +{"text": "One of the greatest achievements of genetics in the 20th century is D.K. Belyaev\u2019s discovery of destabilizing selection during the domestication of animals and that this selection affects only gene expression regulation (not gene structure) and inf luences systems of neuroendocrine control of ontogenesis in a stressful environment. Among the experimental data generalized by Belyaev\u2019s discovery, there are also f indings about accelerated extinc tion of testes\u2019 hormonal function and disrupted seasonality of reproduction of domesticated foxes in comparisonwith their wild congeners. To date, Belyaev\u2019s discovery has already been repeatedly conf irmed, for example, by independentobservations during deer domestication, during the use of rats as laboratory animals, after the reintroductionof endangered species such as Przewalski\u2019s horse, and during the creation of a Siberian reserve populationof the Siberian grouse when it had reached an endangered status in natural habitats. A genome-wide comparisonamong humans, several domestic animals, and some of their wild congeners has given rise to the concept of self-domesticationsyndrome, which includes autism spectrum disorders. In our previous study, we created a bioinformaticmodel of human self-domestication syndrome using differentially expressed genes orthologous to the human genes whose changes inexpression affect reproductive potential, i. e., growth of the number of humans in the absence of restrictions causedby limiting factors. Here, we applied this model to 68 human genes whose changes in expression alter the reproductivehealth of women and men and to 3080 DEGs of domestic versus wild animals. As a result, in domestic animals,we identif ied 16 and 4 DEGs, the expression changes of which are codirected with changes in the expression of thehuman orthologous genes decreasing and increasing human reproductive potential, respectively. The wild animalshad 9 and 11 such DEGs, respectively. This difference between domestic and wild animals was signif icant accordingto Pearson\u2019s \u03c72 test (p < 0.05) and Fisher\u2019s exact test (p < 0.05). We discuss the results from the standpoint of restorationof endangered animal species whose natural habitats are subject to an anthropogenic impact. One of the greatest achievements of genetics in the 20th centurywas D.K. Belyaev\u2019s discovery of destabilizing selectionduring the domestication of animals and his finding that thisselection affects the regulation of gene expression but not gene structure. In thiscontext, destabilizing selection directly or indirectly affectssystems of neuroendocrine control of ontogenesis when preexistingstress factors strengthen or new ones emerge in theenvironment: \u201cIn a genetic and biochemical sense, what maybe selected for are changes in the regulation of genes \u2013 that is,in the timing and the amount of gene expression rather thanchanges in individual structural genes. Selection having suchan effect is called by me destabilizing selection. The selectionbecomes destabilizing when it affects, directly or indirectly,the systems of neuroendocrine control of ontogenesis. Thisseems always to be the case when some new stressful factorsappear in the environment, or when stresses usual for the speciesincrease in strength.\u201d .This discovery is the result of many years of unique experimentson the domestication of the mink and fox as well as the mouse asa laboratory model of human cancer . In these experiments, there were findings about acceleratedextinction of testes\u2019 hormonal function and disturbances in reproduction seasonality of domesticated foxes versus wildfoxes; these experiments were conducted with the participationof a coauthor of the present study.Subsequent comparative analysis of reproductive indicesof domesticated foxes versus wild ones (taken as the norm)revealed decreases in the activity indicators of the femaleendocrine system , in sexual activity offirst-year males , in embryonic gonadmass, and in developmental heterochrony of their pituitarytesticularaxis as evidence of destabilizingselection during the domestication of animals .Additionally, in a laboratory model of animal domesticationinvolving outbred rat strains, a delay in puberty was independentlydocumented in males of a tame strain comparedto an aggressive strain . The resultsof a comparison among the genomes of humans, numerousdomestic animals, and some of their wild congeners havebeen generalized by the term \u201cself-domestication syndrome\u201d,the symptoms of which include autism spectrum disorders, although the idea of humanself-domestication is still subject to debate to this day.Following a trend in the postgenomic era of life sciences, we have created a bioinformatic model ofself-domestication syndrome using differentially expressedgenes (DEGs) \u2013 of domestic animals versus their wild congeners\u2013 that are orthologous to human genes associated withrheumatoid arthritis and with reproductivepotential , i. e., with an increase inthe number of humans when there are no restrictions causedby limiting factors .In the present work, we analyzed 68 human genes whoseexpression changes affect the reproductive health of women and men .The results are discussed in terms of restoration of animalspecies that are disappearing under anthropogenic pressure.The analyzed human genes. We analyzed 68 human genesin the promoters of which we have previously evaluated candidateSNP markers of changes in the reproductive health ofwomen and men ; the examples are presented in Table 1, and completedescriptions \u2013 in Supplementary Material http://vavilov.elpub.ru/jour/manager/files/Suppl_Ponomarenko_Engl.pdf Supplementary Material is available in the online version of the paper:For instance, in the promoter of the human ACKR1 gene, we previously found SNPrs2814778, which lowers the affinity of TATA-binding protein(TBP) for this promoter , thereby lowering the expression of this gene. This finding is consistentwith independent clinical data on patients carrying rs2814778 , and therefore we proposedrs2814778 as a candidate SNP marker of preeclampsiaas one of the most pressing problems of modern obstetrics, which worsens the reproductivehealth of women , as indicatedby the down arrow (\u2193) in column v of Table 1. On the otherhand, according to pathology reports , an excess of the ACKR1 protein contributes toincreased human mortality from atherosclerosis and othercoronary artery diseases , thus reducinghuman reproductive potential .Another example of a gene studied by us earlier , the decrease and increase in expressionof which impair the reproductive system of humans, is ZFY(located on the Y chromosome) encoding a protein with a zincfinger (see Table 1).In addition, we previously found two candidate SNP markers,rs758026532 and rs772821225, in the promoter ofDNMT1 encoding human DNA methyltransferase 1 \u2013 thatreduce DNMT1 expression , as doesanticancer drug decitabine , therebyincreasing the reproductive potential of people . Besides, in the promoter of this gene,we previously found seven candidate SNP markers of DNMT1overexpression , which, according toa mouse model of a human disease ,can cause epigenetic aberrations of fetal brain developmentunder the influence of stressors, thus impairing the humanreproductive system .Finally, in Table 1, readers can see that the previouslystudied PLCXD1 gene (phosphatidylinositol-specific phospholipase CX domain-containing 1)represents a diametrically opposite situation . Indeed,underexpression of this gene is a risk factor for stroke in menof reproductive age , whereas its overexpressionimproves human reproductive potential by suppressingthe progression of melanomas: some of the deadliest humanmalignant tumors .As done for the genes ACKR1, DNMT1, PLCXD1, and ZFYabove, Supplementary Material describes all 68 human genesanalyzed in the present study.The studied DEGs of domestic versus wild animals.A total of 3080 DEGs of domestic versus wild animals wereanalyzed here, which are freely available in the PubMed database, as described in Table 2 and characterizedby examples in Table 3. At the same time, according to , here, RNA-Seq datawere examined in accordance with one of the oldest , widely used , and fundamental concepts of phylogenetic analysis \u2013 \u201cmost recent commonancestor\u201d . In this regard, domestic animalsand their wild relatives were studied by means of oppositely directed equivalent changes in gene expression in comparisonwith their unknown most recent common ancestor.For example, the Ckbl gene (creatine kinase B-like protein)was characterized in column v of Table 1 by a positive scoreof 4.33 log2 units of relative expression in the blood of dogs(Canis familiaris) versus wolves (C. lupus), as reported by. Therefore, dogs and wolves respectivelyshow increased and decreased expression of this gene ascompared to their most recent common ancestor . Likewise, a negative score of (\u20131.55) onthe relative expression of Adm (adrenomedullin) in the dog\u2019sfrontal cortex as compared to the wolf corresponds to decreased and increased expression of this genein this part of the brain during divergence from their mostrecent common ancestor .A total of 450 DEGs in the blood and19 DEGs in the frontal cortex of dogsand wolves were characterized inthis way.The score of (\u20130.47) on the differential expression of theHpd gene, which encodes 4-hydroxyphenylpyruvate dioxygenase,in the pituitary gland of tame versus aggressive foxesVulpes vulpes denotes respectivelydecreased and increased expression of this gene during divergencefrom their most recent ancestor (see Table 3).In addition, positive scores on relative expression of genesMdk and C7 (respectivelyencoding midkine and component 7 of the complementsystem of innate immunity) in the frontal cortex of the pig(Sus scrofa) as compared to the boar (S. scrofa) indicates theirhigher expression in the pig than in the boar when these speciesdiverged from their most recent common ancestor (seeTable 3). On the contrary, the negative score of (\u20131.32) for theAno3 gene in the pituitary gland of the pig compared to theboar denotes respectively a deficiencyand an excess of anoctamin 3 (encoded by this gene) in thispart of the brain when these species diverged from their mostrecent common ancestor (see Table 3).Accordingly, a negative score on the differential expressionof the Agt gene (angiotensinogen) in the frontal cortex ofdomestic guinea pigs Cavia porcellus relative to wild guineapigs C. aperea corresponds to decreasedand increased expression of this gene as these animals divergedfrom their most recent common ancestor . Table 3 provides similar examples ofdescription for some of the 3080 DEGs of domestic animalsversus their wild congeners, as investigated in this work.A search for orthologous genes of humans and animals.For each analyzed DEG of domestic animals versus their wild congeners (see Tables 2 and 3), an orthologous gene wassought among all the 68 studied human genes . If no such orthologous human genewas found, then the animal DEG in question was excludedfrom further analysis. Otherwise, we collated the effects ofcodirected changes in the expression of the found orthologousgenes on the reproductive potential of humans with expressionchanges during the emergence of a domesticated species orduring preservation of the wild species of the respective animalin the microevolution of their most recent common ancestor. For example, the Apoa1gene (apolipoprotein A1) is characterized by a negative scoreof (\u20133.2) on differential expression in domestic versus wildguinea pigs , indicating decreased andincreased expression of this gene, respectively, in the processof their divergence from their most recent common ancestor. Accordingly, underexpressionof a human orthologous gene, APOA1, was clinically associatedwith a predisposition to cognitive disorders , whereas its overexpression correlates with infertilityin women , as illustrated in columns viiand ix of Table 4. Thus, a deficiency and excess of APOA1in humans impair the reproductive system of humans .In the present study, within the framework of the previouslyproposed bioinformatic model of human diseases involvingDEGs of domestic versus wild animals , all of the above means that the expressionchanges of Apoa1 during the divergence of domestic and wildguinea pigs from their most recent common ancestor correspondto a negative impact of expression changes of the humanorthologous gene APOA1 on human reproductive potential.Similarly, the CETP gene encoding cholesteryl ester transferprotein is overexpressed in hypercholesterolemia of pregnancy, thereby impairing the reproductivehealth of women . The excessof CETP in humans is consistent with an excess of Cetp in thedomestic guinea pig during its divergence from the most recentcommon ancestor with the wild guinea pig ,as shown in Table 4 (columns ii and iv). By contrast, a CETPdeficiency in humans is a clinically proven marker of slowingatherogenesis as well as lower risks of stroke and myocardialinfarction ; these correlations can be regarded as factors increasing human reproductive potential. CETP downregulation inhumans is consistent with Cetp downregulation in the wildguinea pig when it diverged with the domestic guinea pigfrom the most recent common ancestor .Finally, the human CYP17A1 gene produces steroid 17\u03b1-monooxygenase,underexpression of which impairs fertility inhumans , thereby reducing their reproductivepotential, as displayed in Table 4. The deficiencyof CYP17A1 in humans is consistent with the deficiency ofCyp17a1 in the domestic guinea pig andin wild chickens Gallus gallus when domestic and wild forms of these animals diverged fromtheir respective most recent common ancestors . On the contrary, a CYP17A1 excess inhumans overcomes subfertility , thus increasinghuman reproductive potential . This influence is consistent with higher expressionof the orthologous Cyp17a1 gene in the wild guinea pig anddomestic chicken as compared with this gene\u2019s expressionduring their microevolution from the corresponding mostrecent common (see Table 4).In Table 4, the reader can find similar descriptions for allthe human and animal orthologous genes that we identifiedamong the 68 human genes under study and among the 3080 DEGs of domesticanimals versus their wild congeners (see Tables 2 and 3). Inthis context, it is noteworthy that because of the concept of\u201cdivergence from the most recent common ancestor,\u201d it waspossible to compare phenotypic manifestations of increasedand decreased expression of human genes with changesin the expression of respective orthologous genes in domesticand wild animals as they diverged from their most recentcommon ancestor .Knowledge base PetDEGsDB on human diseases as candidatesymptoms of self-domestication syndrome. Identifiedhere as the main finding, the matches \u2013 between the effects ofchanged expression of human genes on human reproductivepotential and expression changes of orthologous animal genesduring the divergence of domestic and wild animals fromtheir most recent common ancestors \u2013 were compiled into aflat text Excel-compatible file and were finally transformed inthe MariaDB 10.2.12 Web environment into a knowledge base, named PetDEGsDB,on human diseases that are candidates for self-domesticationsyndrome . This knowledge base is freelyavailable at https://www.sysbio.ru/domestic-wild.Statistical analysis. The correspondences (see Table 4)between the phenotypic manifestations of codirected changesin the expression of orthologous genes of humans and animalswere summarized in a standard Fisher 2\u00d72 table representedby intersections of the rows \u201cdomestic animals\u201d and \u201cwildanimals\u201d . This Fisher 2\u00d72 tablewas analyzed using the Statistica package ; its operating mode was chosen via the sequence ofcommands Statistics \u2192 Nonparametrics \u2192 2\u00d72 Table\u201d, whichenabled us to perform a binomial distribution analysis, Fisher\u2019sexact test, and Pearson\u2019s \u03c72 test .In this work, we examined 68 human genes and 3080 DEGs of domestic animalsversus wild congeners (see Tables 2 and 3), which aredescribed in the \u201cMaterials and methods\u201d section. As a resultof the technique described in the subsection \u201cA search fororthologous genes of humans and animals\u201d , 20 animal DEGs were found that turned out tobe orthologous to the studied human genes, as presented inTable 4 and described in the \u201cMaterials and methods,\u201d withhuman genes APOA1, CETP, and CYP17A1 as examples.Let us review the identified orthologous genes of humansand animals.The human CGC gene codes for glucagon; both a deficiency and an excess ofthis protein are clinically proven markers of a reduced pregnancyrate and hence impairment of the reproductive systemin humans (see Table 4). Upregulation and downregulationof glucagon in humans are consistent with increased and decreasedexpression of Gcg in domestic and wild guinea pigs during their divergence from their mostrecent common ancestor.The IL1B gene codes for interleukin 1\u03b2. An excess of thisinterleukin increases circadian sensitivity to pain , thereby reducing human reproductive potential(see Table 4). By contrast, IL1B deficiency prevents bonedeformation during bacterial invasion ,thus expectedly increasing human reproductive potential(see Table 4). The excess and deficiency of IL1B in humansare the expression changes codirected with the upregulationand downregulation of Il1b in the wild guinea pig during itsdivergence with the domestic guinea pig from a commonancestor .The NR5A1 gene encoding human steroidogenic factor 1is characterized by underexpression in gonadal dysgenesis, which reduces human reproductivepotential (see Table 4), whereas overexpression of the NR5A1protein improves sperm quality . Boththe NR5A1 deficiency and excess in humans are consistentwith the decreased and increased expression of Nr5a1 inthe domestic guinea pig in the process of divergence withthe wild guinea pig from a common ancestor .The PROC gene represents human coagulation factor XIV,a deficiency of which in neonates can cause deadly purpurafulminans , whereas its overexpressionincreases miscarriage risk . These alterationsof PROC expression are in agreement with the decreasedand increased expression of Proc in wild and domestic guineapigs during their microevolution (seeTable 4).The GH1 gene codes for growth hormone, which increasesthe reproductive potential of women . Theexcess of GH1 in humans is similar to the excess of Gh1 indogs (C. familiaris) when compared to the most recent commonancestor of dogs and wolves (C. lupus) . GH1 deficiency increases human mortality from cardiovasculardisease in line with Gh1deficiency in wolves during their microevolution.Genes HBB and HBD encode hemoglobin subunits \u03b2 and \u03b4.Their deficiency is associated with thalassemia, a contributingfactor of poor reproductive potential in women . Human hemoglobin deficiency is consistent withhemoglobin underexpression in dogs and domestic chickens whencompared with the most recent common ancestors for theirwild counterparts (see Table 4). Conversely, an excess ofhemoglobin in humans is in agreement with overexpressionof hemoglobin in wolves and wild chickens (see Table 4).The human ESR2 gene (estrogen receptor 2) \u2013 both in thecase of underexpression in adolescents and in the case of itsoverexpression in this segment of the population \u2013 was associatedwith decreased sperm quality in adults . These alterations of its expression in humans areconsistent with those of an orthologous gene, Esr2, in tameand aggressive foxes during their microevolution(see Table 4).The IL9R gene encodes human interleukin 9 receptor, thedeficiency of which disrupts trophoblast implantation , whereas its excess contributes to deadly anaphylacticshock . The upregulation anddownregulation of this receptor in humans are consistent withincreased and decreased expression of the Il9r gene in tameand aggressive foxes as they divergedfrom their most recent common ancestor (see Table 4).The F7 gene encodes proconvertin. Its recombinant activatedform is used as an emergency life-saving modalityagainst obstetric bleeding . Upregulationof F7 in humans is consistent with that of its ortholog in wildrabbits in the process of divergence with domestic rabbitsfrom a common ancestor . A proconvertindeficiency accompanies spontaneous life-threatening bleeding and is consistent with F7 deficiencyin domestic rabbits (see Table 2).The F3 gene (thromboplastin) is overexpressed in strokeand myocardial infarction and thus mayreduce human reproductive potential (see Table 4). An excessof F3 in humans is consistent with an excess of F3 in domesticchickens . On the other hand,thromboplastin deficiency contributes to an increase in humanreproductive potential , in agreement withF3 deficiency in wild chickens during their divergence withdomestic chickens from the most recent common ancestor.The PGR gene codes for progesterone receptor. A humandisease model based on Pgr knockout rats features infertilitydue to impaired sexual behavior . PGRdeficiency in humans is codirected with Pgr deficiency in wildchickens during their divergence from a common ancestor withdomestic chickens . A humanfertility model based on ewes revealed a positive correlationbetween Pgr and fertility . Upregulation ofPGR in humans is consistent with Pgr overexpression in domesticchickens as a consequence of their selection by humansfor egg production (see Table 4).The SLC25A6 gene encodes human steroidogenic factor 1.Its overexpression correlates with resistance to the herpesvirus , in line with Slc25a6 overexpressionin domestic chickens compared to their most recent commonancestor with wild chickens . AnSLC25A6 deficiency is accompanied by an increased risk ofmuscle dystrophy in agreement withthe Slc25a6 underexpression in wild chickens as compared totheir most recent common ancestor with domestic chickensselected for muscle growth by humans.All the results of this study are summarized in Table 5,where we present domestic animals\u2019 16 and 4 DEGs thechanges in expression of which are consistently codirectedwith changes in the expression of the orthologous genes inhumans that respectively decrease and increase human reproductivepotential. By contrast, in the wild animals, therewere 9 and 11 such DEGs, respectively . This difference between wildand domestic animals is statistically significant according toPearson\u2019s \u03c72 test (p < 0.05) and Fisher\u2019s exact test (p < 0.05).Finally, the binomial distribution analysis ( p < 0.01) indicatesthat the anthropogenic living conditions of animals during theirdomestication usually alter gene expression in a direction correspondingto the expression changes of human orthologousgenes that decrease reproductive potential.On the contrary, microevolution of wild animals in a naturalhabitat has changed the expression of genes equally often inthe directions that either decrease or increase reproductivepotential, judging from expression changes of respective humanorthologous genes . Thisfinding is in agreement with the generally accepted choice ofthe wild type as the norm.While discussing this result, we should note, first of all,that in laboratory animal models of human diseases, DEGsare usually detected in inbred strains having symptoms of adisease in comparison with outbred strains as the norm .Nevertheless, in the literature, we were unable to find unequivocalevidence that codirected changes in the expressionof orthologous genes cause similar pathologies in humans andanimals, probably owing to different genetic contexts of thesechanges in different species.Among parameters of the harmful anthropogenic impacton animal populations, a decrease in their effective size isoften mentioned, which promotes their inbreeding, which inturn negatively correlates with sperm quality, for example, inthe domestic cat Felis catus , deerCervus elaphus , and finch Taeniopygiaguttata as well as in Mexicanwolves (Canis lupus baileyi), which disappeared from the wildin the 20th century and exist only as part of a program fortheir restoration and reintroduction into their former habitats.When endangered cranes Grus americana are reintroduced,a high degree of inbreeding of their ex situ population delays the onset of reproduction, and as aconsequence, decreases egg production; this problem is expectedto be overcome by sperm cryopreservation and artificialinsemination .For the feline family Felidae, sperm cryopreservation andartificial insemination have already been successfully implementedfor the reintroduction of the endangered wild catPrionailurus bengalensis euptilurus . The creation of protected areas for natural habitatsof the Amur tiger Panthera tigris altaica has contributed tothe restoration of its population . Due toan anthropogenic reduction in the geographic range of theFlorida cougar Puma concolor coryi, only ~20 individuals areleft. On the basis of theoretical populational calculations , individuals of the closely related Texas cougarP. concolor couguar were transported to restore this species,thereby ensuring the success of the reintroduction .Crossing of subspecies has facilitated the reintroductionof Przewalski\u2019s horses Equus caballus przewalskii, whichdisappeared from the wild half a century ago .As a continuation of these successes, we can cite examplesof the comparison of genomic diversity of inbred with outbred populations of the bull Bos taurus, comparisons of F1descendants (from crosses between them) and descendants ofF1 backcrosses with parental populations, as well as similarcomparisons for the bison (Bison bison). The results of thesestudies independently confirm the finding of a decrease inthe inbreeding degree when inbred strains of animals arecrossed with their outbred relatives .Finally, through the deciphering of the genome in the AustrianFleckvieh bull Bos (primigenius) taurus, geographic locationsinfluencing sperm quality were identified, and interbreedingoptions were found that improve this quality .An increase in mortality from infections, as, for example,at the beginning of the reintroduction of Przewalski\u2019s horses,is a much less studied parameter of the negative anthropogenicimpact on animal populations .Besides, during the creation of a reserve population of theSiberian grouse Falcipennis falcipennis, which had been onthe verge of extinction in natural habitats, the intestinal microbiotaof these birds changed, acting as a stressor of the immunesystem . An analysis of phylogeneticinertia of the infection\u2013host network revealed an increase inthe number of common infections of humans and domesticanimals with the growing number of new tamed animals;this increase may be an epidemiological bridge connectingthe anthropogenic environment with wildlife .Finally, a possible counterargument to the above notion ofa decrease in the reproductive potential of animals under theinfluence of humans is the domestic pig, which surpasses thewild boar in sperm quality . The reasonis selection for fertility for the sake of meat. Another counterargumentis an increased proportion of females among domesticchickens in comparison with wild chickens as a consequenceof selection for egg production .All of the above means that the decrease in reproductivepotentialduring the domestication of new economically valuablespecies of animals ) canbe compensated either by artificial selection for fertility in additionto the main desired trait or through interbreed crosses.When natural habitats of wild animals are included into economicland rotation by humans, an inbreeding-related diminutionof their reproductive potential takes place (up to extinction),which can be compensated by subspecies crossings ofthese animals and by methods of assisted reproductive technology.We examined 68 human genes and 3080 DEGs of domestic animals versus theirwild congeners. 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Phylogenet.Evol. 2021;163:107257."} +{"text": "The key factor of genome instability during aging is transposon dysregulation. This may be due to senile changes in the expression of lamins, which epigenetically modulate transposons. Lamins directly physically interact with transposons. Epigenetic regulators such as SIRT7, BAF, and microRNA can also serve as intermediaries for their interactions. There is also an inverse regulation, since transposons are sources of miRNAs that affect lamins. We suggest that lamins can be attributed to epigenetic factors, since they are part of the NURD, interact with histone deacetylases and regulate gene expression without changing the nucleotide sequences. The role of lamins in the etiopathogenesis of premature aging syndromes may be associated with interactions with transposons. In various human cells, LINE1 is present in the heterochromatin domains of the genome associated with lamins, while SIRT7 facilitates the interaction of this retroelement with lamins. Both retroelements and the nuclear lamina play an important role in the antiviral response of organisms. This may be due to the role of lamins in protection from both viruses and transposons, since viruses and transposons are evolutionarily related. Transposable elements and lamins are secondary messengers of environmental stressors that can serve as triggers for aging and carcinogenesis. Transposons play a role in the development of cancer, while the microRNAs derived from them, participating in the etiopathogenesis of tumors, are important in human aging. Lamins have similar properties, since lamins are dysregulated in cancer, and microRNAs affecting them are involved in carcinogenesis. Changes in the expression of specif ic microRNAs were also revealedin laminopathies. Identif ication of the epigenetic mechanisms of interaction of lamins with transposons duringagingcan become the basis for the development of methods of life extension and targeted therapy of age-associatedcancer Nuclear lamina (NL) is a protein network connected to theinner side of the cell\u2019s nuclear envelope. Nuclear laminaperforms structural, signaling and regulatory functions. Thestudy of the evolution of NL components made it possibleto discover a wide variety of domains and sequence architecturesthat go beyond the classical alpha-helices . Nuclear lamina is composed of lamins and associatedproteins . The main componentsof NL are lamins . Their genes werepresent at the earliest stages of eukaryotic evolution. Laminshave been identified in multicellular organisms, amoebas, andprimitive opistocontes such as Ichthyosporea and Choano-flagellates . Lamins are required not only tomaintain the shape of the nucleus, but also to control replicationand transcription. Lamins are proteins of the family ofintermediate filaments (class V) with a specific structure. Inmammalian cells, 4 types of lamins are expressed: A and C(splicing isoforms of one gene), B1 and B2 . Minor isoforms \u0410\u03b410 and \u04212 are also known. Theprotein precursor of lamin A is prelamin A. Its C-terminalregion is post-translationally modified: farnesylated, carboxymethylated.Proteolysis of the CaaX motif of pre-laminA also occurs using the metalloprotease ZMPSTE24. Lamins A, \u0421, \u0410\u03b410 and \u04212 are encodedby LMNA gene .Proteins that interact with lamins and are closely associatedwith them functionally include LBR (lamin B receptor),BAF (barrier to autointegration factor), SUN1, SUN2,nesprin. They are involved in the structural organization ofthe nucleus and in the regulation of nuclear processes. LBRand endoprotease prelamin A have enzymatic properties.At the periphery of the nucleus, genomic DNA binds tolamins A and B, forming heterochromatic domains. Lamin Aalso binds to chromatin inside the nucleus \u2013 the nucleoplasmicenvironment is represented mainly by euchromatin,which indicates the role of lamin A in the regulation ofgene expression of the entire genome .Lamin B interacts with genomic domains that are relativelygene-poor and transcriptionally inactive . It is assumed that in the last common predecessor ofall eukaryotes (LECA \u2013 last eukaryotic common ancestor),the configurations of the nuclear envelope and the associatedNL played an important role in determining the activity ofthe nucleus.In the subsequent evolution, there were changes in themechanisms of regulation of gene expression of lamins indifferent taxa. The protein diversity of lamins in plants andtrypanosomes is taxonomically limited, while in multicellularanimals it is manifested in a wider range. The phylogenetictree of lamina genes is characterized by verticalevolution. For example, two lamins in protists from stronglydiverging taxa have targets in mammalian cell nuclei andpolymerize into filamentous structures, which indicates thefunctional preservation of distant homologues of lamins.In certain groups of eukaryotes, a pronounced evolutionaryplasticity of the structures of the NL was determined by themechanisms of chromatin binding and epigenetic controldue to a high level of divergence of lamins\u2019 homologues.Lamin changes occur with aging and in age-associateddiseases such as malignant neoplasms. For example, in lungcancer, significant reductions in lamin B1 levels are found. Lamin A regulates the activity ofmTOR (mechanistic target of rapamycin), the low activityof which contributes to an increase in life expectancy.Inhibition of mTOR leadsto the degradation of defective molecules and organellesthat accumulate in cells during aging, since low autophagyactivity is a characteristic feature of aging-related diseases.Lamins can be attributed to epigenetic factors, since theyensure the inheritance of the functional status of the gene.For example, the attachment of lamin B1 to specific genomeloci leads to transcription suppression of genes located inthem. Most differentially expressed genes are activated dueto the loss of lamin B1. These include the genes of the REToncogene and its corepressor GFR\u03b11. Therefore, when laminB1 is depleted with aging, the risk of tumors increases.Another mechanism of RET activation is H3K27me3 histonemethylation .Epigenetic factors include chromatin remodeling, modificationsof histones and DNA nucleotides, and the influenceof non-coding RNAs (ncRNAs). During cellular senescencein mammals, H3K56ac and H4K16ac levels decrease, whichcontributes to altered gene expression, genomic instability,and telomere damage. Aging is accompanied by a globaldecrease in DNA methylation levels, coinciding with agerelatedloss of heterochromatin. As a result, the regulationof gene expression and activation of transposable elements(\u0422\u0415s) is disrupted. At the same time, the participation oflamins in epigenetic regulation associated with aging occurs through direct interaction with chromatin in regions ofspecific DNA sequences called lamin-associated domains(LADs).Lamins also promote epigenetic changes during agingthrough functional interactions with sirtuins. For example,lamin A enhances the deacetylase activity of SIRT1, stimulatesthe functioning of SIRT6 in DNA repair, and recruitshistone deacetylase 2 (HDAC2). Lamins A/C are also directparticipants in epigenetic regulation, since they serveas components of the NURD (nucleosome remodelingdeacetylase complex). This complex also includes HDAC1,RBBP4, RBBP7 . Lamins A/C interactwith histone deacetylase 2 (HDAC2) and with PCAF acetyltransferase(p300-CBP associated factor) . Lamin B1 recruits the PRC2 (Polycomb repressivecomplex 2) complex, through which the H3K27me3 landscapechanges with repression of specific genes involved insignaling and cell migration .The development of progeria in patients with germinalmutations in the genes of lamins proves the role of laminsin regulation of life expectancy. Progeroid laminopathies(PLs) are characterized by premature aging and death fromcomplications of atherosclerosis such as myocardial infarction,stroke, or heart failure. PLs are usually not inheritedbecause patients do not survive to puberty.An important genetic feature of progeria is telomereshortening with each replication cycle .The most famous of these diseases is Hutchinson\u2013Guildfordprogeria (HGP), which is characterized by significant telomereshortening. The disease is diagnosed from two yearsof age, when noticeable symptoms of premature aging aredetermined. Life expectancy in HGP patients is 10\u201320 years.In 90 % of HGP patients, mutations in the LMNA gene aredetermined . The frequency of occurrenceof HGP is 1 in 8 million newborns .The most common mutation in LMNA gene is C1824T,which leads to accumulation of progerin (the dominantnegative form of lamin A).Interestingly, progerin also accumulates in cells duringphysiological aging as one of the rare splicing forms oflamin A transcripts. However, in comparison with physiologicalaging, more severe epigenetic changes occur inHGP, such as covalent modifications of histones with atendency to loss of separation into hetero- and euchromatin.These epigenetic changes lead to changes in the spatialcompartmentalization and conformation of chromatin inthe nucleus. These processes involve microRNAs, such asmiR-9, which can be used as a target for brain protection inHGP patients . MiR-9 interacts withthe 3\u2032-untranslated region (UTR) of lamin A mRNA withoutaffecting lamin C. 3\u2032-UTR region of prelamin A contains anadditional binding site for miR-9. In experiments on miceand human HeLa cell cultures, it was proved that miR-9expression significantly reduces the levels of lamin A .As with normal aging, abnormal accumulation of progerinsuppresses the interactions of lamin A with SIRT1, HDAC2,and SIRT6. In addition, in patients with HGP, the regulationof the heterochromatin protein HP1 is impaired, the levels ofH3K9me3 decrease, and the NURD function is suppressed(of which lamin A/C is a component). At the same time, therelationship of lamin A/C with HDAC2 causes the activationof the CDKN1A gene, which is the most important determinantof cellular senescence .Mutations in LMNA gene also cause atypical Werner\u2019ssyndrome (AWS), mandibuloacral dysplasia type A (MADA),atypical progeria syndrome (APS) . Theydiffer in disease-specific mutations in LMNA gene and inclinical manifestations. Dunnigan-type familial partiallipodystrophy is caused by an R482W missense mutationin lamin A, leading to a pathological change in its effect onthe periphery and inside the nucleus on a three-dimensionalrearrangement of chromatin . MADAcan be caused by mutations in the LMNA or ZMPSTE24genes. It is a rare autosomal recessive disorder characterizedby bone abnormalities with localized osteolysis and generalizedosteoporosis, skin pigmentation, lipodystrophy, andaccelerated aging. These mutations cause accumulation ofprelamin A, which leads to disruption of chromatin dynamics.Similar changes are found during physiological aging.Progeroid laminopathies are also caused by mutationsin genes that interact with lamins. For example, Nestor\u2013Guillermo progeria (NGPS) is caused by mutations in theBAF gene . Premature aging syndromescan be caused not only by mutations in the genes of laminsand proteins interacting with them, but also by mutationsin the genes of DNA repair and maintenance enzymes. Forexample, mutations in helicase genes cause Rothmund\u2013Thomson syndrome (RECQL4 gene), Bloom syndrome(BLM gene), Werner syndrome (WRN gene). Mutations inDNA repair genes cause Dyskeratosis congentia and Cockayne syndrome (ERCC8 orERCC6 genes). In contrast to these premature aging syndromes,PLs are characterizedby an early onset, more severemanifestations of aging and a lack of predisposition to cancer. All PLs are characterized by generalizedosteoporosis and osteolysis, crowding of teeth with malocclusion.Progeroid laminopathies with a specific lesion ofthe musculoskeletal system include heart-hand syndromeof Slovenian (HHS-S) . Mutationsin the ZMPSTE24 gene are causes of the development ofrestrictive dermopathy (RD) and mandibuloacral dysplasiatype B (MADB) .In ataxia-telangiectasia patients, accumulation of laminB1 causes changes in the shape of the nucleus and cellaging. Oxidative stress in this syndrome increases lamin B1levels by stimulating mitogen-activated protein kinase p38(p38 MAPK). In cell experiments using the MAPK activatoranisomycin and the MAPK inhibitor SB203580 todetermine the effect of p38 MAPK on lamin B1 levels,p38 MAPK activation was shown to significantly increase lamin B1 levels. At the same time, inhibition of p38 MAPKdecreases lamin B1 levels. Using the PLA method (proximityligation assay), it was proved that p38 MAPK interactswith lamin B1, causing its phosphorylation . These changes also occur during natural aging. Also,PLs are characterized by decrease in perinuclear heterochromatinand increase in cellular senescence \u2013 two conditionsthat correlate with dysregulation of TEs . It can be assumed that in evolution, lamins arose asone of the protective mechanisms aimed at silencing TEsto protect hosts from genomic instability . Therefore, laminopathies that cause premature agingand aging-associated pathology are most likely to cause activationof TEs as a key mechanism for the development ofdiseases . Indeed, in an experimenton cell models expressing progerin characteristic of HGP,a pronounced increase in the expression of LINE, SINE,HERV and DNA transposons was revealed .Transposable elements are elements capable of transpositionwithin the genome. There are two classes of TEs: retroelements(REs), transposed by reverse transcription andintermediate RNA; DNA-TEs, transposed using transposaseby the mechanism of excision and insertion . All TEs are subdivided into autonomous (containgenes of transposition enzymes) and non-autonomous (useprotein products of other TEs for their transpositons). Retroelementsare classified into those containing LTR \u2013 LTR-REs and non-LTR-REs. The mostcommon autonomous non-LTR-REs in the human genomeare LINE1 (long interspersed nuclear elements), and nonautonomousones are SINE .LTR-REs includes human endogenous retroviruses(HERV) . Silencing of TEs is normallyensured by the degradation of their RNA and the formationof heterochromatin. Therefore, TEs are characterized byactivation during aging of organisms as a result of ageassociatedderegulation of heterochromatin and microRNA.The relationship between TEs activation and aging wasfound in termites. Reproductive queens live for tens of yearswithout a significant increase in TEs expression, while workingtermites live for only a few weeks, which is due to TEsdysregulation in their genomes due to changes in piRNAexpression . Interestingly, in the somaticcells of Cnidaria, which are characterized by almost un-limitedregeneration and immortality, piRNA and Piwi proteinsare also expressed. It is accompanied by low levels ofTEs activity in their genomes. These properties were revealedin Hydra vulgaris . Piwi homologuesnamed Cniwi are found at all stages of developmentof Podocoryne carnea not only in reproductive cells, butalso in differentiated somatic cells . Sincethe DNA repair systems in Cnidaria do not have a specificefficiency that distinguishes them from other animals, it can be assumed that the expression of piRNA in their organismsis the cause of delayed aging processes .During human aging, there is a progressive activationof LINE1, which leads to the activation of the interferonresponse due to the accumulation of LINE1 cDNA. Thesechanges are the cause of aseptic inflammation and theactivation of interferon observed during aging . At the same time, an increase in the level ofproinflammatory cytokines in myeloid immune cells in thethymus during aging is accompanied by a gradual decreasein the level of lamin B1, which specifically functions forthe correct organogenesis of the thymus by maintainingthe expression of epithelial cell genes. It was found thata decrease in the level of lamin B1 leads to an increase intranscription of 533 genes and suppression of expression of778 genes. Analysis of these genes showed their participationin cell adhesion, development of the immune system,differentiation of T-lymphocytes and cytokine production. Interestingly, chronic inflammation isalso characteristic of PLs. In this case, the STAT1-regulatedinterferon-like response is induced by DNA hybrids: RNAthrough the signaling pathways cGAS (cyclic GMP-AMPsynthase) and STING (stimulator of interferon genes) .Transposable elements are the most important sensorsof environmental stressors, exerting an adaptive regulatoryeffect on protein-coding genes . According to the theory of \u201cbuffering function ofthe tail of lamins\u201d, NL acts as an intracellular sensor of thereactive oxygen species (through conservative changes in thecysteine residue in the tail domain of the lamin). Throughoutmammalian phylogeny, three cysteine residues at the C-terminus of lamin A are conserved. Of these,C588 and C591 are also characteristic of other vertebrates,and C522 is absent in non-mammalian animals.Experiments on human skin fibroblasts showed that theseamino acids in the functional tail domain of lamin A increasethe sensitivity to reactive oxygen species, and their replacementwith alanine promotes cellular aging . Thus, lamins and TEs are sensors for stressors thatcan cause their dysregulation. Moreover, abnormalities inthe expression of TEs and lamins can potentiate each other,contributing to aging. Indeed, in experiments on Drosophila,the relationship between the age-related decrease in lamin Band the activation of various REs was proved .Aging can be induced not only by decreased levels oflamins, but also by their increased production . REs are also characterized by similar properties.For example, in the study of 111 known REs in young andold Drosophila, not only an increase in the expression of18 specific REs was determined, but also a decrease in thelevels of other 18 REs . That is, withaging, there is not just an activation of TEs or a decrease inthe levels of lamins, but a variety of changes in their expression,which potentiate each other.The question arises as to what is primary \u2013 dysregulationof lamins or TEs. Investigation of the relationship betweenlamins and TEs could provide a basis for identifying the keymechanisms of physiological aging and for the developmentof new ways to prolong life. It is possible that changes inthe levels of lamins and TEs expression during aging is acorrelation rather than a causal relationship; however, theavailable data on their interconnections suggest a mutualpotentiation of these structures during aging.In different cells, LINE1s in the human genome are abundantin the lamin-associated domains of heterochromatinregions at the nuclear periphery. Sirtuin SIRT7 is involvedin epigenetic transcriptional repression of LINE1 throughoutthe genome. The interaction of SIRT7 with A/C laminsplays an important role in this process. At the same time,SIRT7 provides deacetylation of H3K18, facilitating the interactionof LINE1s with NL. Deacetylation of H3K18 isinsufficient to suppress LINE1s expression in the absence oflamins A/C, and depletion of lamins leads to transcriptionalactivation of LINE1s. That is, for the repression of LINE1s,their relationship with lamins A/C is necessary .During the supercompactisation of differentiating humanneutrophils genomes, centromeres, percentromeres, andLINEs move to the NL region. This property is retained forLINE in LBR-deficient cells, but is lost for other heterochromatinregions . Human retroelementsLTR7/HERV-H, LTR5_Hs, and L1HS form specific regulatoryregions in the genome that selectively and site-specificallybind to lamin B1, as well as to NANOG homeobox,POU5F1, and CCCEC-binding factor .There is also an inverse relationship where lamin B maintainsthe integrity of the nuclear genome by repressing TEs,which was found in experiments on Drosophila . Prelamin A is interconnected with TEs throughBAF, which inhibits the integration of retroviruses. BAF isalso found in protein complexes containing Sleeping Beautytransposase . BAF is required to modulatethe effect of prelamin A on chromatin structure because itinduces histone H3K9 trimethylation, as well as nuclearrelocalization of the lamin-associated proteins LAP2-\u03b1 andHP1-\u03b1 .Lamins and transposons are sensors of environmental stresseffects, characterized by their interconnection and possiblepotentiation of dysregulation during aging. Therefore, it isnecessary to consider other possible mechanisms affectingtheir activity during aging. Environmental factors causingdysregulation of lamins and TEs include exogenous viruses.Determination of the role of lamins in viral infection canbecome the basis for identifying possible new ways of antiviraltherapy, as well as the use of viral vectors for correctingaging processes by acting on specific lamins.Induction of lamins A/C occurs in naive CD4+ T cellsupon antigen recognition. In this case, lamins A/C act as alink between the nucleus and the plasma membrane duringthe activation of T cells. In experiments on mice, the role oflamins A/C in the response to vaccinia virus was revealed. Proteins hnRNP and laminsA/C serve as carriers and mediators for the movementof p17 protein of avian reovirus between the nucleus andthe cytoplasm . The latency of HIV-1after integration is characterized by reversible silencingof transcription driven by the LTR of the HIV genome.The lamin-interacting protein SUN2 maintains repressivechromatin and inhibits the transcription of proviral DNA,which is regulated by HIV LTR through its association withlamins A/C. Lamins A/C bind SUN2 to nucleosomes andto HIV-1 5\u2032-LTR, which causes blockages of viral initiationand elongation of transcription .The release of herpesviruses from the nucleus is accompaniedby a change in the architecture of the NL . Herpes simplex virus-1 induces phosphorylationand reorganization of lamins A/C through the virulencefactor \u2013 the product of the y134.5 gene. It allows the virusto exit through the nucleus . In turn, laminsfacilitate the access of capsid to the inner nuclear membraneand the curvature of its sections around the capsid of theherpes virus during budding .TRIM E3 ligase controls the replication of HSV-1 herpesvirusesby affecting the integrity of lamins through changesin the structure of the host cell centrosomes. TRIM43ubiquitinates the centrosome protein pericentrin, causingits proteasome degradation. It leads to lamins changes thatsuppress the active state of viral chromatin .The mechanism of this phenomenon is due to the specificinteraction of lamin A/C with the genomic DNA of the virusat the nuclear periphery. In this case, lamin inhibits the formationof heterochromatin in the region of HSV promoters.Caspase-6-dependent dephosphorylation of lamins A/Cis essential for SV40 virus penetration . Baculovirus promotes phosphorylation of lamin Band destruction of NL during infection .Canine parvovirus in the late stage of infection reorganizesNL with decreasing the levels of lamins A/C in the apicalpart of the nucleus .The interrelation of lamins with viruses may indicate thepossible participation of NL in the interconversion of viruseswith TEs, as well as in transposon-controlled regulatorynetworks of genomes. Like lamins, TEs are involved in antiviralresponse, which may be related to their phylogeneticrelationship. In the course of evolution, LTR-REs becamesources of exogenous retroviruses .ERV of various mammalian species are capable of convertinginto infectious form of viruses and converting back toREs . Expression products of LTRREsenv genes cause restriction of exogenous retrovirusesin animals . Retroelements enzymes can also be used to integrate exogenous viruses into hostgenomes . Exogenous viruses canregulate TEs activity. For example, human cytomegaloviruscauses tissue-specific activation of LTR-RE . MicroRNAs can serve as possible mediators in theinteractions of viruses with TE and lamins. Investigation ofmicroRNAs is promising both for the development of methodsfor slowing aging processes and for antiviral therapyMicroRNA are involved in regulation of lamins and TEs. It may be due to theorigin of miRNAs in evolution from transposons. For the firsttime, evidence of the emergence of 55 different microRNAsfrom human TEs was obtained in 2007 . In 2009, 73 human microRNAs derived from TEswere identified . In 2011, 191 microRNAsthat arose from TE were identified .In the same year, another research group identified 226 humanmicroRNAs derived from TE (MDTEs) . In 2012, 235 human MDTEs were identified , 409 MDTEs were identified in 2015 , 34 MDTEs were identified in 2020. In 2016,the MDTE database was created. This database containsinformation about microRNAs originated directly from TEs.Aging is an important risk factor for the developmentof oncopathology. It may be due to common epigeneticmechanisms, since during aging, global DNA hypomethylation,TEs activation, and the development of genomicinstability occur . This assumption canbe confirmed by data on the role of the same microRNAsin both carcinogenesis and aging. A lot of information hasbeen accumulated on the association of various microRNAswith the development of tumors. Bioinformation databaseOncomiR was created (www.oncomir.org) . We analyzed 410 different microRNAs featured inOncomiR using the MDTE database . Asa result, we found that 94 of these microRNAs were derivedfrom TEs. It indicates the role of these microRNAs in thedevelopment of malignant tumors and the possibility of theiruse as a target for antitumor therapy.Like TEs, lamins also play a role in carcinogenesis. Itwas shown that a deficiency of lamins A/C can be used asan independent risk factor for the development of cervicalcancer . Lamin B1 levels are significantlyincreased in patients with hepatocellular carcinoma. Lamin B2 is highly expressed innon-small cell lung cancer and positively correlates withlymph node metastases. It is due to the interaction of laminB2 with cyclin D1, which activates G9\u03b1 expressionand increases H3K9me2 levels. As a result, H3K9me2 bindsto the promoter region of the E-\u0441adherin CDH1 gene andstimulates cell migration .In gastric cancer, lamin B1 expression is reduced intumor tissue, and low levels of lamin B1 are significantlycorrelated with clinical stage severity, depth of invasion, andpoor prognosis. In the experiment, inhibition of lamin B1causes the proliferation and migration of gastric cancer cells,which is due to the activation of the PI3K/PTEN/Akt andMAPK/ERK pathways, as well as the suppression of p53/h21WAF1/CIP1 .Low levels of lamins A/C expression in cancer are specificfor poor prognosis. In breast cancer (BC), the loss ordecrease in the expression of lamins A/C was significantlyassociated with large tumor sizes, poor prognosis and thedevelopment of long-term results . Comparison of osteosarcoma andosteoblast cell lines showed a lower level of lamin A expressionin osteosarcoma cells. Elevated lamin A levels reducecancer cells\u2019 ability to migrate .Thus, carcinogenesis is associated both with an increaseand (most often) with a decrease in lamin expression, thatis, it is explained by their dysregulation.This is due to the global regulatory role of lamins in theexpression of various genes. Therefore, it is important todetermine the specific features of changes in the expressionof lamins in each type of tumor in order to target themduring antitumor therapy. Most tumors are characterized bydecreased lamins expression, which may be one of the keymechanisms of initiation and maintenance of carcinogenesis,because lamins serve as host defense systems for TEssilencing. Therefore, the loss of control by the lamins leadsto pathological activation of TEs with subsequent genomicinstability and tumor development. The effect of increasedlevels of lamins on tumor development is probably due tothe possibility of opposite regulatory effects of lamins onTEs, depending on localization of TEs in active or repressedgenome regions .Like transposons, during aging and carcinogenesis, laminsare also associated with changes in microRNA levels. Forexample, the target of the oncogenic miR-129, the expressionof which is increased in BC, is lamin A. The target of theoncogenic miR-218, the level of which decreases in BC, islamin B1 . LMNA expression in breastcancer cells is suppressed by miR-9, which leads to the progressionof the disease due to changes in the deformabilityof the nucleus and an increase in the invasive ability ofcells . MiR-122 inhibits hepatocellularcancer cell proliferation by suppressing the expression oflamin B2 . MiR-351-5p regulates lamin B1expression and promotes phloxuridine-induced tumor cellapoptosis . In fibroblasts associated withBC, the expression of miR-222 is increased . The direct target of this microRNA is LBR.Therefore, miR-222 is considered for BC targeted therapy.During human aging, the levels of LMNB1 protein productsin fibroblasts and keratinocytes of the skin decrease,which is mediated by the influence of miR-23a . An increase in LMNB1 expression due to geneduplication in autosomal dominant leukodystrophy in adultsleads to progressive brain demyelination. This is due to the role of lamin B1 in regulation of myelin formation and maintenanceduring aging. The targets of miR-23a are also thePTEN gene transcript (phosphatase and tensin homolog onchromosome 10) and long noncoding RNA 2700046G09Rik. MiR-124-3p complementarily binds to3\u2032-UTR of LMNA gene, suppressing its expression . Activation of miR-141-3p during replicativesenescence decreases the activity of HDAC1 and HDAC2.MiR-141-3p has a targeted regulatory effect on ZMPSTE24endoprotease prelamin A .Like TEs, miRNAs affect lamins according to the principleof mutual regulation, since miRNAs genes are located in genomeregions associated with lamins. For example, in mice,aging-associated miRNA genes are located on the X chromosomein a cluster located in the lamin-associated domain. Long noncoding RNA Xist is involved inX chromosome inactivation by directly interacting with theLBR and recruiting it to the NL. It leads to remodeling ofthe three-dimensional structure of DNA, which allows Xistto distribute along the X chromosome and cause silencingof transcriptionally active genes .In skeletal muscles of patients with muscular dystrophiescaused by mutations in LMNA gene, pronounced dysregulationof sixteen different microRNAs was revealed, whichare involved in Wnt-signaling pathways, MAPK, and theregulation of transforming growth factor \u03b2. Nine of these microRNAsare involved in regenerative processes and are detected at high levels in fetal muscles . Expression of the mutant allele of LMNA gene(mutation R482W) is accompanied by an increase in levelsof miR-335, which has antilipogenic properties . Significantly increased expression of let-7a-5p,miR-142-3p, miR-145-5p, and miR-454-3p is observed inpatients with familial dilated cardiomyopathy associatedwith mutations in LMNA .According to the MDTE database, among the miRNAsassociated with lamina pathology, the origin from LINE2was proven for miR-192 and miR-502, the origin from MIR(SINE-RE) was proven for miR-335 . Itshould be noted that miR-335 also plays a role in humanphysiological aging and age-associated neurological pathology. It may be due to the role of laminsin protecting genomes from transpositions , since TEs are involved in the epigenetic regulationof lamins. That is, the structural and functional relationshipbetween lamins and TEs is mutually regulatory. On the onehand, lamins are involved in the control of TEs activity. Onthe other hand, TEs can exert an epigenetic regulatory effecton NL, which may be due to the influence of microRNAsderived from TEs.Lamins play an important role in driving gene expressionand in TEs silencing, thereby preventing genome instability.Therefore, dysregulation of lamins, mainly associated withinactivating mutations in their genes or a decrease in theirexpression, leads to TEs activation. Therefore, pathologicalactivation of TEs and the resulting genomic instabilityplay an important role in changing the levels of lamins inmalignant neoplasms. The role of lamins in viral infectionsupports this assumption, since TEs are phylogeneticallyassociated with viruses.Transposable elements and lamins share common properties,such as dysregulation during aging and carcinogenesis,as well as interactions with microRNAs. Mutual regulationof lamins and TEs testifies to the mutual potentiation oftheir dysregulation in laminopathies, carcinogenesis andphysiological aging. 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Haring is the third author of this article due to contributions to the conceptualization, methodology, statistical analysis and writing of the published manuscript.The final authorship on this manuscript is: A.L. Gianakos, B.N. Saad, R. Haring, L.G. Menken, S. Elkattaway, F.A. Liporace, R.S. Yoon.At the time the study was completed, all authors had an affiliation with City Medical Center-RWJ Barnabas Health, Jersey City, New Jersey, USA.The authors regret this error. In this regard, the original article has been updated."} +{"text": "Scientific Reports 10.1038/s41598-021-85988-8, published online 25 March 2021Correction to: Victor Birlanga was omitted from the author list in the original version of this Article.The Author Contributions section now reads:N. perurans protein database. V.B extracted N. perurans DNA, developed the OTU graph and aided in the results interpretation. K.N.D and O.S wrote the manuscript and critical revision was provided by A.T, I.O.C, E.MC, N.B and E.D.\u201d\u201cA.T, I.O.C, E.MC, O.S designed the experiments. K.N.D collected and maintained amoeba isolates and performed the protein extractions. K.N.D and O.S analysed and processed the raw mass spectrometry data. E.D provided statistical input on the mass spectrometry analysis. N.B provided the The original Article and the Supplementary Information file that accompanies the article have been corrected."} +{"text": "Dipterisshenzhenensis, a new species of ferns from Shenzhen, Guangdong, southern China, is identified and described. It closely resembles D.chinensis but possesses several unique traits, such as long rhizome scales, castaneous stipe, and abaxially pale fronds with two fan-shaped fronds connected by a broad wing. Molecular evidence showed that D.shenzhenensis is allied to D.conjugata, whereas it has morphologically significant differences (P < 0.05) on the basis of quantitative trait statistical analysis. Overall, the morphological evidence, taken together with the result of cpDNA indicated that D.shenzhenensis is a distinct species. Dipteris Reinw. is one of two genera in Dipteridaceae , Global Biodiversity Information Facility (https://www.gbif.org/), and JSTOR (https://plants.jstor.org/). Voucher specimens were deposited in the National Orchid Conservation Center of China (NOCC) and Shenzhen Fairy Lake Botanical Garden Herbarium (SZG).The features of rhizome scales were obtained using a Leica M205A dissecting microscope. Morphology of spores was observed with Phenom Pro scanning electron microscope after being sputter-coated with gold. Measurements were made from mature and intact specimens. For length and width of lobes, each specimen was measured six times using ImageJ software , followeDipterisconjugata Reinw. (Cheiropleuriaintegrifolia (D. C. Eaton ex Hook.) M. Kato, Y. Yatabe, Sahashi & N. Murak. (cpDNA) regions were extracted, amplified and sequenced following PCR) amplification and sequencing are shown in Table cpDNA sequences were assembled and edited using SeqMan v.7.1.0 , then aligned using MEGA v.7.0 (PP) were performed with the first 25% of samples discarded as burn-in.Ten samples, representing five species were used in this study. Apart from the sequences of a Reinw. and the . Murak. were dowGA v.7.0 . AlignmeGA v.7.0 , and besGA v.7.0 was usedGA v.7.0 integratGA v.7.0 with fouDipterisshenzhenensis has been confused with D.conjugata and D.chinensis because of similar gross morphology. This is especially true of dried herbarium specimens. Most specimens of D.shenzhenensis were formerly identified as D.chinensis in herbaria because of the presence in similar fronds morphology. We studied most online specimens of these three species and conducted quantitative trait statistical analysis. The result showed that D.conjugata displayed significant differences compared to D.shenzhenensis and D.chinensis in the length of lobes (LL) (P < 0.0001), the width of lobes (WL) (P < 0.0001), and the number of lobes for each half of the fan-shaped fronds (NL) (P < 0.0001) , with the significant difference being in the LL (P < 0.0001) and the NL (P < 0.05) Fig. , Table 3sis Fig. . Most noris Figs and 3.rbcL, atpA, rps4, rbcL-accD, and trnG-trnR). With the Cheiropleuriaintegrifolia as outgroup, the phylogram showed that Dipteris can be classified into four well-supported clades. Dipterisshenzhenensis was typically well supported as monophyletic and strongly supported as sister to D.conjugata (PP = 1.0) , in the base and color of fronds , and in stipe color (castaneous vs. stramineous to brown).The new species is similar to Y. H. Yan et al. YYH15638 China. Guangdong Province: Shenzhen City, Mt. Qiniangshan, elev. ca. 82 m, 16 August 2020, Plants. terrestrial on rocks, 0.5\u20131.0 m tall. Rhizome. long-creeping, ca. 1 cm in diam., densely scaly. Rhizome scales. spreading, dark brown to black, stiff, margin almost entire, 6.8\u20138.0 \u00d7 0.09\u20130.27 mm, lanceolate, apex long acuminate, acumen up to 2\u20133 mm long; Stipe. glabrous except at the very base, castaneous, 30\u201385 cm. Fronds. slightly funnel-shaped, divided into 2 fan-shaped fronds, each half deeply divided into 4 to 5 unequal lobes, lobes shallowly divided one or more times, with 8\u201310 ultimate lobes in each half of lamina, abaxially glabrous and pale; base with broad wings; venation reticulate, visible on both surfaces, prominent abaxially. Lobes. margins serrate, apices acute, 4.5\u201312.0 \u00d7 10.5\u201317.0 cm, reticulated venation network. Spores. spreading, monolete, 18.5\u201319.0 \u00d7 37.5\u201339.0 \u03bcm, glabrous.So far only known from Shenzhen City, Guangdong Province, southern China. It is distributed in Mt. Qiniangshan, growing on rocks at elevation of 70\u2013200 m in evergreen broad-leaf forest.Shen-zhen-shuang-shan-jue (\u6df1\u5733\u53cc\u6247\u8568).Dipterisshenzhenensis was discovered in the City of Shenzhen located in Guangdong Province, southern China. The specific epithet, therefore, is from this city name.Dipterisshenzhenensis is currently found in only one location in Mt. Qiniangshan, Shenzhen City, Guangdong Province, southern China. The predicted Area of Occupancy (AOO) for the species is no more than 5,000 m2. This species prefers to grow in low and opening mountain areas and is very likely to experience human disturbance. Over the past 20 years, the authors have observed that D.shenzhenensis showed signs of decline with the recovery of macrophanerophytes in Mt. Qiniangshan. Following the International Union for Conservation of Nature (IUCN) Categories and Criteria .Criteria , we regaY. H. Yan et al. YYH15637 (NOCC!); loc. cit., elev. ca. 200 m, 27 December 2003, Y. H. Yan 1937 (HUST!); loc. cit., elev. ca. 150 m, 8 November 2002, Y. H. Yan 885 (HUST!); loc. cit., 17 August 2002, S. Z. Zhang et al. 011036-A1 ; loc. cit., elev. ca. 75.38 m, 18 November 2015, L. Jiang & JL00328Y. P. Chen ; loc. cit., elev. ca. 70 m, 22 February 2003, S. Z. Zhang et al. 012037-A ; loc. cit., elev. ca. 70 m, 22 February 2003, S. Z. Zhang et al. 012037-B ; loc. cit., 31 March 2000, F. W. Xing & Y. X. Zhang 12374 . s. coll. 0685742 China. Guangdong Province, Shenzhen City, Mt. Qiniangshan, elev. ca. 90 m, 16 August 2020,"} +{"text": "The non-native vascular plants of Murmansk Region (European Russia) are under active investigation towards the compilation of the first complete checklist. This work is part of the project 'Flora of Russian Lapland', which ultimately aims at the complete inventory of the taxonomy, distribution and status of vascular plant species in Murmansk Region, based on the comprehensive database of herbarium specimens, field observations and literature.Anthemisruthenica, Aruncusdioicus, Bromuscommutatus, Chaerophyllumhirsutum, Galegaorientalis, Geumaleppicum, Leonurusquinquelobatus, Lepidiumdensiflorum, Levisticumofficinale, Myrrhisodorata, Phleumphleoides, Prunusarmeniaca, Rorippasylvestris, Seneciovernalis) are reported as new to Murmansk Region. The historical occurrences of alien plants appeared in the territory largely as contaminants (of seed or forage). In particular, Rorippasylvestris and Seneciovernalis arrived with the forage imported during the Second World War. All recent occurrences originated by escape from confinement , reflecting a high diversity of the modern assortment of cultivated plants in commerce and private gardens. Regarding the invasion status, five alien species are considered casual and eight species are treated as locally established or persisting (for uncertain time). Only one species, Galegaorientalis, is considered naturalised and capable of further spreading in the territory, although without invasive potential.New territory-level records of non-native vascular plants emerged during our inventory of herbarium collections and recent fieldwork. Fourteen species ( Non-native plants have become a serious issue at the global scale, disturbing native ecosystems, human well-being and economy . With thThe number and percentage of non-native vascular plants in Europe is overwhelming. According to the latest continent-scale inventory , there w2, thus exceeding in size some European countries like Greece. Geographically, Murmansk Region occupies the Kola Peninsula with the neighbouring mainland, being surrounded by the Barents Sea in the north and the White Sea in the south and east. It is situated within the Subarctic Zone, almost completely north of the Arctic Circle, and is covered by the transition gradient from tundra along the northern coast, through forest tundra in the major part of the mainland, to northern taiga in the south situated in the north-western part of European Russia Fig. . Its arehe south . Two sigThe vascular plants of Murmansk Region have been in focus for over 150 years; this territory received its first checklist already in 1831 , which wDespite this impressive progress in floristic studies, non-native vascular plants of Murmansk Region have never been completely inventoried. The last published synopsis of vascular plants of this territory includedIn course of preparation of the first checklist of non-native vascular parts in Murmansk Region (part of the project 'Flora of Russian Lapland'), we continued our fieldwork and survey of herbarium collections in order to enhance the database of occurrences of the vascular plants. While cataloguing the collections at the University of Helsinki (H), barcoding the collections at the Avrorin Polar-Alpine Botanical Garden-Institute (KPABG) and scanning the collections at the Komarov Botanical Institute (LE), we discovered a few specimens which had previously escaped the attention of botanists working with the flora of the region.Among the unfiled collections kept at Avrorin Polar-Alpine Botanical Garden-Institute (KPABG), we have found a large set of herbarium specimens which provided the documentation to the inventory of weedy plants in Russian Lapland made by E.V. Shlyakova in the 1950s and the early 1960s. She extensively studied weeds in Murmansk Region and otheThe present contribution is a complement to The new information on non-native vascular plants in Murmansk Region was collected by M.N. Kozhin in the field during his work on the project 'Flora of Russian Lapland' in 2018-2020 , all available herbarium collections at H, KPABG and LE (acronyms according to Species are treated according to the methodology and data structure similar to that employed by https://laplandflora.ru/). The herbarium specimens were deposited and partly imaged at H, INEP, KAND, KPABG, MW (https://plant.depo.msu.ru/) and LE (http://en.herbariumle.ru/). The new records were georeferenced and made available through GBIF within curatorial datasets .Europe (temperate), Mediterranean, Caucasus.Europe (north), Asia.In Karelia, the species is known as casual on railways . In FinlE. Shlyakova #36 (KPABG 042732).Russia. Murmansk Region. Kola District. Tuloma Village, state farm 'Tuloma', field no. 1, cultivated field of perennial grasses, 31.08.1953, Transport \u2013 Contaminant: Seed contaminant.The species was found on fields, thus indicating its arrival with contaminated seed.USSR, after the Second World War (1945-1991).This casual alien has not been known prior to the period of its first record and had hardly had a chance for longer survival in the agricultural habitats.Historical casual occurrence. No new records, apparently extinct in the territory.Sands, rock outcrops, disturbed ground.Annual. Therophyte with taproot. FernaldAF85FB1F-E30D-5C5B-971B-9F41DF11ACC5urn:lsid:ipni.org:names:20973-2https://laplandflora.ru/#19949https://www.gbif.org/occurrence/3400181306AruncusdioicusActaeadioica Walter, Fl. Carol.: 152 (1788). Fernald, Rhodora 41: 423 (1939) - AruncusdioicusAruncussylvesterAruncusdioicusAruncusasiaticusEurope (temperate), Caucasus, Northern Asia , Himalayas, China, South-Eastern Asia.Commonly cultivated for ornamental purposes and occasionally runs wild in Europe and North America.Seldom runs wild in North-Western European Russia .33.58224\u00b0N, 67.57926\u00b0E, near buildings, 15.07.2020, M. Kozhin M-4412 .Russia. Murmansk Region. Kirovsk District. Highway Apatity - Kirovsk, abandoned airport 'Kirovsk', Escape from confinement: Ornamental purpose other than horticulture.This is a popular ornamental plant, which can survive for a long time after planting without further management.USSR, after the Second World War (1945-1991).This is a popular garden plant of the Soviet times, which was known as capable to self-seed and persist in abandoned cultivation for a long time, but its subspontaneous occurrence has never been formally reported in floristic works in Murmansk Region.The species was originally introduced in 1937 into the Polar-Alpine Botanical Garden and was known to self-seed around the places of original cultivation without spreading into other anthropogenic or native landscapes .Our record is a remnant of abandoned cultivation, similarly maintaining itself locally without expansion.Temperate forb forests.Perennial polycarpic. Hemicryptophyte with short rhizome.Schrad.DAD2A9DE-062D-56DA-A423-E24901F7E66Aurn:lsid:ipni.org:names:393635-1https://laplandflora.ru/#28335https://www.gbif.org/occurrence/3400181308Bromuscommutatus Schrad., Fl. Germ. 1: 353 (1806).Mediterranean, western Asia, Caucasus, Iran.Fully naturalised (archeophyte) in Atlantic and Temperate Europe. Casual in Northern Europe and Northern Asia; established in North and South America, Southern Africa, Australia.Rare casual in southern Finland , southerE. Shlyakova #72 (KPABG 042581).Russia. Murmansk Region. Kandalaksha District. Kovda Village, collective farm 'Belomor', potato field in use of Demidov, solitary, 13.08.1953, Transport \u2013 Contaminant: Seed contaminant.The species was found on fields, thus indicating its arrival with contaminated seed or planting material.USSR, after the Second World War (1945-1991).This record is linked to the intensification of agriculture in the USSR after the war time. Its long-term survival in agricultural habitats is considered highly unlikely.Historical casual occurrence. No new records, apparently extinct in the territory.Xerothermic meadows.Annual. Therophyte with fibrous roots.Bromusarvensis L., but the collected specimen clearly differs from the latter species in the longer (up to 1 mm) pubescence on the leaf sheaths and the longer (5-8 mm) awns. Based on the compact racemes, the broadly angulate margin of lodicules and the larger (ca. 21 mm) spicules and (5-10 mm) lodicules, the specimen belongs to B.commutatus H.Scholz, was recently separated in Central and Southern Europe .Europe .Northern Europe.Rare casual in southern Finland, apparently arrived with transport .33.39388\u00b0N, 67.57378\u00b0E, thickets of hogweed at the edge of the small-wooded willow, 23.06.2020, M. Kozhin & E. Borovichev M-4406 .Russia. Murmansk Region. Apatity Town. Northern part of Akademgorodok near the road along Kozlov Street, near the car depot, Escape from confinement: Ornamental purpose other than horticulture.The species is a popular ornamental plant of recent times, cultivated in populated places as tall forb for flowers and foliage Fig. .Russia (after 1991).This introduction is firmly linked with the recent cultivation of this ornamental plant, which was not used in the USSR.Persisting population in a man-made habitat (populated place).Riversides, moist forests.Perennial polycarpic. Hemicryptophyte with caudex and short rhizome.Chaerophyllumhirsutum 'Roseum'. Its garden origin is, therefore, beyond doubt.This species is represented by a cultivated variety with pink flowers, Lam.AC30B776-F60B-5B3D-B13B-433F7CC9DA15urn:lsid:ipni.org:names:495682-1https://laplandflora.ru/#21395https://laplandflora.ru/#28300https://laplandflora.ru/#28301https://www.gbif.org/occurrence/3400181311https://www.gbif.org/occurrence/3400181305https://www.gbif.org/occurrence/3400181301Galegaorientalis Lam., Encycl. 2(2): 596 (1788).Caucasus .Information incomplete due to the recent time of invasion. Reported as commonly running wild and established in, for example, Finland and EuroIn Finland, this species commonly runs wild in the whole country, up to its northern part . It is cRussia. Murmansk Region. Apatity Town:33.37094\u00b0N, 67.54942\u00b0E, field overgrown with dandelions, cereals and bedstraw, 23.06.2020, M. Kozhin & E. Borovichev M-4405 .Polar Experimental Station of Institute of Plant Industry, 33.32479\u00b0N, 67.57402\u00b0E, roadside between willow stands separating the fields, 500 m south-west of the road, 13.07.2020, M. Kozhin M-4408 .Fields of the state farm 'Industry' at the entrance to Apatity Town, 33.32641\u00b0N, 67.5765\u00b0E, road between fields, 13.07.2020, M. Kozhin M-4409 .Fields of the state farm 'Industry' at the entrance to Apatity Town, Escape from confinement: Agriculture. Escape from confinement: Research.The species was cultivated as a forage plant and subsequently escaped from cultivation. In Murmansk Region, it was originally introduced into experimental cultivation (laboratory) in the Polar-Alpine Botanical Garden in 1939 . By 1990Galega was carried out at the Polar Experimental Station of the Institute of Plant Industry and the new variety \"Zapolarnyi\" was bred. This variety was recommended for commercial cultivation in the northern agricultural regions of Russia .The species started to escape during the period of its commercial cultivation for forage, which became common in the latest 20 years.Established alien, naturalised in anthropogenic habitats. Potentially invasive but not expanding into natural habitats.Tall forb of mountain meadows.Perennial polycarpic. Hemicryptophyte with caudex and root sprouts.Jacq.06E1DDA3-5FC1-5318-9EF9-0098A1A6358Aurn:lsid:ipni.org:names:30094401-2https://laplandflora.ru/#28329https://www.gbif.org/occurrence/2028619743Geumaleppicum Jacq., Collectanea 1: 88, t. 127 (1787).Eastern Europe , Northern Asia, North America.Central and Northern Europe.In Finland, this species occurs as an established neophyte in the southern part of the country . In KareM. Piirainen 6061 (H 827871).Russia. Murmansk Region. Lovozero District. Revda Village (SW part), close to the museum buildings, 02.08.2011, Transport \u2013 Stowaway: People and their luggage/equipment.This zoochorous species is a ruderal plant commonly found along pedestrian paths. Revda is a large village with many people employed in mining, and with tourist attractions as, for example, a museum of local studies, near which the species has been found. We, therefore, assume that the plant was transported to the place of occurrence on people visiting the village.Russia (after 1991).Considering the capability of this species to establish and spread further, we assume that its introduction was very recent.According to the collector's notes, a sparse population of the species was observed. The species was considered as a locally established neophyte.Forest margins and meadows.Perennial polycarpic. Hemicryptophyte with short rhizome.Gilib.827E4BE0-3E2C-596E-BD69-E446BE2190EDurn:lsid:ipni.org:names:449227-1https://laplandflora.ru/#16291https://laplandflora.ru/#16292https://laplandflora.ru/#16291https://plant.depo.msu.ru/open/public/item/MW1058418https://www.gbif.org/occurrence/2907937106https://www.gbif.org/occurrence/2876127028Leonurusquinquelobatus Gilib. in Usteri, Delect. Opusc. Bot. 2: 321 (1793).LeonurusquinquelobatusLeonurusvillosusLeonuruscardiacasubsp.villosusLeonurusquinquelobatusLeonuruscardiacaLeonuruscardiaca L. s. str. by its calyces and stems with abundant long hairs throughout and lower cauline leaves deeply divided into narrow lobes (vs. dissected into broad lobes) (The species differs from d lobes) .Crimea, Caucasus, Iran.Europe, Asia.Locally established neophyte in southern Finland and sout66.598067\u00b0N, 34.834799\u00b0E, on a seashore meadow in a holiday village, 05.07.2018, M. Kozhin M-4036 .Russia. Murmansk Region. Terskii District. Kuzreka Village, near Botaminskaya fishing station, Escape from confinement: Ornamental purpose other than horticulture.The species has been traditionally cultivated as folk medicine, although nowadays it practically fell into disuse and can seldom be found in cultivation.Russia (after 1991).The record originated from a well-explored area, from which the species has not been known in the previous times. Its introduction is therefore considered recent.Locally established neophyte, persisting but not spreading far from the original place of introduction.Mountain forests and shrublands.Perennial polycarpic. Hemicryptophyte with short rhizome.Leonurusquinquelobatus in Murmansk Region, which was based on a specimen collected from Umba Village. That plant was a misnamed specimen of L.cardiaca L. s.str.Schrad.3EF5A1D8-BC3B-544B-B49E-9DB57F0336D1urn:lsid:ipni.org:names:286137-1https://laplandflora.ru/#28328https://www.gbif.org/occurrence/1948467413Lepidiumdensiflorum Schrad., Index Seminum Horti G\u00f6ttingen. 1832: 4 (1832).Lepidium by the absence or near absence of petals, the absence of smell, larger fruits (ca. 3\u20133.5 mm long) in dense racemes .Russia. Murmansk Region. Kandalaksha Town. SE side of the crossing of Ulitsa Gor'kogo and Ul. Pronina, surroundings of a gas station, Transport \u2013 Stowaway: Vehicles .Russia (after 1991).This species was recorded from the place with intense transport activity, in current use. Its very recent introduction is therefore beyond doubt.Only a few individuals were observed. The collector's notes suggested a casual occurrence.Open places, river sands, disturbed grasslands.Annual . Therophyte with taproot.W.D.J.KochF3161853-65D1-56E7-818B-F7A74E36F7B5urn:lsid:ipni.org:names:844187-1https://laplandflora.ru/#19923https://www.gbif.org/occurrence/3400181302LevisticumofficinaleLigusticumlevisticum L., Sp. Pl. 1: 250 (1753). W.D.J.Koch, Nova Acta Phys.-Med. Acad. Caes. Leop.-Carol. Nat. Cur. 12(1): 101 (1824) - Iran.Europe, China, North America, South America.Established alien in southern Finland . Casual 33.55772\u00b0N, 67.58224\u00b0E, birch grass forest near the spring, 15.07.2020, M. Kozhin M-4410 .Russia. Murmansk Region. Kirovsk District. Highway Apatity - Kirovsk, 9th km, Escape from confinement: Agriculture.Frequently cultivated as a salad herb, a vegetable or a spice (lovage). This particular occurrence may be of secondary origin (arrived with relocated waste).Russia (after 1991).It is uncertain how long-persisting this population is. The bad habit of placing garden and household waste along roadsides is relatively new in the Russian North, so we linked this record with the recent decades.Locally established alien, introduced into natural habitats.Riversides.Perennial polycarpic. Hemicryptophyte with caudex and short rhizome.(L.) Scop.5C550C1F-116E-5E86-B01E-BDE934D64EB3urn:lsid:ipni.org:names:845120-1https://laplandflora.ru/#28299https://www.gbif.org/occurrence/3400181304MyrrhisodorataScandixodorata L., Sp. Pl. 1: 257 (1753). (L.) Scop., Fl. Carniol., ed. 2. 1: 207 (1771) - Europe (temperate), Mediterranean.Europe, North America.Naturalised in south-western Finland, casual in central Finland and southern Karelia .33.39388\u00b0N, 67.57378\u00b0E, thickets of hogweed at the side of a small-wooded willow, 23.06.2020, M. Kozhin & E. Borovichev M-4407 .Russia. Murmansk Region. Apatity Town. Northern part of Akademgorodok near the road along Kozlov Street, near the car depot, Escape from confinement: Ornamental purpose other than horticulture.Cultivated as an ornamental plant for flowers and foliage.Russia (after 1991).Chaerophyllumhirsutum.This is a place of recent cultivation of this ornamental plant, same as for Persisting population in a man-made habitat (populated place).Mountain forb forest.Perennial polycarpic. Hemicryptophyte with caudex.The species forms large stands Fig. .(L.) H.Karst.EDC5506A-C031-529C-9AE5-EB5D48E5671Aurn:lsid:ipni.org:names:415866-1https://laplandflora.ru/#28333http://rr.herbariumle.ru/01128388https://www.gbif.org/occurrence/3400241301PhleumphleoidesPhalarisphleoides L., Sp. Pl. 1: 55 (1753). (L.) H.Karst., Deutsche Fl. 4: 374 (1881) - PhleumphleoidesPhleumboehmeriCentral and Southern Europe, Mediterranean, Eastern Europe (temperate), Northern Asia (temperate), Central Asia.Northern Europe, northern part of Northern Asia (established), North America .Archeophyte in south-western Finland, neophyte in south-eastern Finland . In KareO. Polyanskaya (LE 01128388).Russia. Murmansk Region. Khibiny Mts., vicinity of Khibinogorsk [Kirovsk] Town, wasteland on the north slope of Takhtarvumchorr Ridge, by the way from the bank of Malyi Vud'yavr Lake to Molybdenum Mine, 14.07.1934, Transport \u2013 Contaminant: Contaminated bait.The species was found in disturbed places along the road before the Second World War, thus indicating its possible import with hay.USSR, before the Second World War (1918-1941).This occurrence is strictly casual and can be linked with the period of recording, when imported hay was still commonly used for local horse transportation.This is a historical record of early casual occurrence. No new records, apparently extinct in the territory.This species is native to the steppe biome and occurs in grasslands.Perennial polycarpic. Hemicryptophyte, laxly cespitose.Although this specimen was deposited in a public collection and revised by all experts, it was not taken into account by the Flora of Murmansk Region or taxonPhleumboehmeri Wibel, which is a synonym of P.phleoides : 2 (1783). L., Sp. Pl. 1: 474 (1753) \u2013 Central Asia, China.Europe (temperate), Mediterranean, Asia Minor, Caucasus, Iran, Australia.Previously, this species was frequently found as casual (young seedlings) along railway tracks in Karelia and NortRussia. Murmansk Region.Yu. D. Gusev (LE01127282);Apatity Railway Station, northern outskirts, on a railroad track, 30.07.1970, A. Notov & D. Sokolov (MW 0384230).Kandalaksha District. Poyakonda Railway Station, along the railway track, 24.08.1993, Transport \u2013 Contaminant: Food contaminant.The species has repeatedly arrived to the territory through waste from human consumption.USSR, after the Second World War (1945-1991); Russia (after 1991).The species has been introduced many times and in many places through human waste. Its recording period corresponds to the times of the high availability and popularity of dried apricots.Strictly casual, ephemerous. Juvenile individuals have been observed.Semi-arid mountain forest.Tree. Phanerophyte.The specimen collected by Gusev in 1970 had not been taken into account in a timely manner and was not included in (L.) Besser19A296ED-96D2-56E6-98E1-509B67C255B5urn:lsid:ipni.org:names:288692-1https://laplandflora.ru/#28332https://www.gbif.org/occurrence/3400181307RorippasylvestrisSisymbriumsylvestre L., Sp. Pl. 2: 657 (1753). (L.) Besser, Enum. Pl.: 27 (1822) \u2013 Europe , Caucasus.Europe , Mediterranean, Central Asia, Siberia, Russian Far East, North America.This species is naturalised in southern Finland and NortO. Kuzeneva & A. Dryakhlova 282 (KPABG 024968).Russia. Murmansk Region. Kandalaksha District. Vicinity of Alakurtti Village, left bank of Tumcha River, along the shore of the stream, 25.07.1957, Transport \u2013 Contaminant: Contaminated bait.The species has arrived with forage transported to the place of occurrence by the German army during the Second World War.Second World War (1941-1945).The period of introduction is established through the pathways.Naturalised, locally established in native habitats. Historical occurrence.The local population of this perennial colonist species persisted for at least 13 years by the time of its discovery. Its current state is unknown.Riversides, floodplains.Perennial polycarpic. Hemicryptophyte with root sprouts.Rorippasylvestris was recorded as locally established in a former German military camp, where it arrived to the territory during the Second World War with forage supply (hay) (In northern Finland (Kuusamo), ly (hay) . We assuWaldst. & Kit.F8BE1536-B8E9-52E8-8AC7-5BECE673DB76urn:lsid:ipni.org:names:248179-1https://laplandflora.ru/#28330https://www.gbif.org/occurrence/1948436060SeneciovernalisSenecioleucanthemifoliussubsp.vernalis Greuter, Willdenowia 33(2): 247 (2003). Waldst. & Kit., Descr. Icon. Pl. Hung. 1: 23, t. 24 (1800) - Europe (temperate), Mediterranean, Caucasus, Iran.Europe , sometimes elsewhere in the world.Rare casual in Karelia, likely introduced during the Second World War . Casual C. E. Sonck 6061 (H 761596).Russia. Murmansk Region. Pechenga District. 'Lapponia Petsamoensis, J\u00e4niskoski, ent. leirialue', 22.08.1957, Transport \u2013 Contaminant: Contaminated bait.The species has arrived with forage transported to the place of occurrence by the German army during the Second World War.Second World War (1941-1945).The period of introduction is established through the pathways.Locally established, persisting. Historical occurrence.The local population of this annual species persisted for at least 13 years by the time of its discovery. Its current state is unknown, but presumably extinct.Open ground, disturbed ground.Annual . Therophyte with taproot.Imatranvoima was contracted to construct these electric plants and operated a few villages of Finnish construction workers in the territory, including J\u00e4niskoski. Carl Erik Sonck, at that time a medical doctor and amateur botanist, served for the business and collected in this territory in the 1950s L\u2019H\u00e9r. L\u2019H\u00e9r. .Rosa (specimens kept at H and S), which were overlooked during the data collection for the pan-European project Atlas Florae Europaeae , Apatity (KPABG), Moscow (MW) and Saint-Petersburg (LE). Although these collections have already been screened for overlooked occurrences e.g. , there iuropaeae . In thaturopaeae .th century . Seed contamination had been declining already in the second half of the 20 century , now bei century , includi century .Rorippasylvestris and Seneciovernalis. Both species are currently known as widely distributed garden weeds or ruderal plants, whereas their occurrence in Murmansk Region is limited to the territory which was impacted by the Second World War. Such plants, called polemochores is a highly popular and common ornamental since the late Soviet times, which should have technically been listed earlier. Our records of the other species reflect the recent developments in Russian horticulture, which are apparently connected with the economic uprising and the corresponding development of trade and more sophisticated greening of urban areas and private gardens; the same phenomenon has been previously noted in Britain by The remaining records reflect our field activities which aim at documenting the current process of plant invasions in the Russian North. All these recent occurrences originated by escape from confinement , reflecting the high diversity of modern cultivation practices in commerce and private gardens. Ornamental cultivation has been constantly increasing its role in global plant invasions , whereasGalegaorientalis, is considered fully established and capable of further spreading in the territory, although without invasive potential.Among the occurrences reported here, five alien species are considered casual and eight species are treated as locally established or persisting (for uncertain time). Only one species, Due to unresolved uncertainties in the background material, we cannot provide the exact number of non-native vascular plants in Murmansk Region yet. So far, we estimate that it slightly exceeds 500 species, including archeophytes and the most recent neophytes.9B13CF3D-4970-5F3B-BC64-4C7F84E5916910.3897/BDJ.10.e78166.suppl1Supplementary material 1New records of non-native vascular plants in Murmansk Region, RussiaData typeoccurrencesFile: oo_619570.txthttps://binary.pensoft.net/file/619570Mikhail N. Kozhin, Alexander N. Sennikov"} +{"text": "Nature Communications 10.1038/s41467-021-25177-3, published online 24 August 2021.Correction to: In this Article the Competing interests statement inadvertently omitted a statement for M.T.L. and L.E.D. The competing financial interests for M.T.L. should have read: \u2018M.T.L. is a founder and limited partner in StemMed Ltd. and a manager in StemMed Holdings, its general partner. He is a founder and equity stakeholder in Tvardi Theraeutics Inc. Some PDXs are exclusively licensed to StemMed Ltd. resulting in royalty income to M.T.L.\u2019. The competing financial interests for L.E.D. should have read, \u2018L.E.D. is a compensated employee of StemMed Ltd\u2019. The PDF and HTML versions of the Article have been corrected."} +{"text": "Proc. R. Soc. B288, 20210839. (Published online 28 July 2021) (doi:10.1098/rspb.2021.0839)Proc. R. Soc. B 288, 20210839. http://doi.org/10.1098/rspb.2021.0839In the paper Roi Harel, J. Carter Loftus and Margaret C. Crofoot 2021. Locomotor compromises maintain group cohesion in baboon troops on the move. The required change is to change the first institution for all of the authors from Department of Ecology, Evolution and Behavior, The Life Sciences Institute, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 9190401, Israel to Department for the Ecology of Animal Societies, Max Planck Institute of Animal Behavior, B\u00fccklestra\u03b2e 5, Konstanz 78467, Germany."} +{"text": "Nature 10.1038/s41586-021-03465-8 Published online 6 October 2021Correction to: In the version of this article initially published, the Acknowledgements section was incomplete and has now been amended to include the following: \u201cNIH BRAIN Initiative awards U01 MH121282 to J.R.E and M.M.B, U19 MH114831 to J.R.E. and E.M.C., U19 MH114830 to H.Z., U01 MH114819 to G.F., 1U01MH114828 to K.Z. and J.C., RF1MH123220 to M.H. and R.H.S., and U19 MH114821. NIH awards R01DC019370 to R.H., R24MH114815 to R.H. and O.R.W., and R24 MH114788 to O.R.W. Nancy and Buster Alvord Endowment to C.D.K.\u201d The changes have been made to the HTML and PDF versions of the article"} +{"text": "Dryadaula Meyrick, 1893 from China are described: Dryadaulaauriformissp. nov., D.flavostriatasp. nov., D.hirtiglobosasp. nov. and D.securiformissp. nov. Photographs of adults and genitalia of the new species are provided. DNA barcodes of D.auriformissp. nov., D.hirtiglobosasp. nov. and D.securiformissp. nov. are given. A key to the species in China and a detailed checklist for the genus with all 49 known species in the world are presented.Four new species of the genus Dryadaulidae was proposed by Tineoidea. It currently includes two genera: Dryadaula Meyrick, 1893 (45 species with worldwide distribution) and Brachydoxa Meyrick, 1917 . The New Zealand genera Eschatotypa Meyrick, 1880 (three species), Eugennaea Meyrick, 1915 (one species) and Sagephora Meyrick, 1888 (six species) were also considered to belong to this group in the genus Dryadaula was reported from Hong Kong, China .The holotypes of COI gene amplification followed that described in our previous study , Berlin, Germany;ZMUCZoological Museum, University of Copenhagen, Denmark.Dryadaulaauriformis sp. nov., a paratype of D.hirtiglobosa sp. nov. and two paratypes of D.securiformis sp. nov. were successfully sequenced and yielded a barcode of 604 bp. Complementary public sequences of D.heindeli Gaedike & Scholz , D.terpsichorella (Busck) and D.visaliella (Chambers) from BOLD systems were used to calculate the genetic distance barcode divergence. Sequence divergences are presented in Table D.visaliella within three Barcode Identification Numbers (BINS) might represent different species, as members of them show higher divergences from each other and were not well distinguished by barcodes.The holotype of Taxon classificationAnimaliaLepidopteraTineidae\ufeffMeyrick, 1893E3D3E547-FFA2-55C2-8A4D-D65FE4B78691DryadaulaDryadaulaglycinopa Meyrick, 1893, by monotypy. TL: Australia . Meyrick, 1893: 559. Type species: CyaneCyanevisaliella Chambers, 1873, by monotypy. TL: United States (Kentucky). Chambers, 1873: 112. Synonymised by ChorocosmaChorocosmamelanorma Meyrick, 1893, by monotypy. TL: Australia (Sydney). Meyrick, 1893: 560. Synonymised by DitrigonophoraDitrigonophoramarmoreipennis Walsingham, 1897, by original designation. TL: Grenada . Walsingham, 1897: 117. Synonymised by ChoroplecaCyane Chambers, 1873. Synonymised by Durrant, 1914: 366. Objective replacement name for OpsodocaOpsodocametrodoxa Meyrick, 1919, by original designation. TL: Guyana. Meyrick, 1919: 270. Synonymised by DiachalastisChoropleca Durrant by Clarke, 1971: 221. Synonymised by Diachalastistetraglossa Meyrick, 1920, by monotypy. TL: Fiji. Meyrick, 1920: 363. Synonymised as ThermocratesThermocratesepischista Meyrick, 1936, by monotypy. TL: Japan (Kyushu). Meyrick, 1936: 620. Synonymised by Robinson, 1988: 74. Type species: ArchimeessiaArchimeessiazinica Zagulajev, 1970, by original designation. TL: Azerbaijan. Zagulajev, 1970: 658. Synonymised by StrophalingaTineaglycinocoma Merick, 1932, by original designation. TL: Ethiopia. Gozm\u00e1ny & V\u00e1ri, 1973: 9. Synonymised by Dryadaula is a small-sized moth, with wingspans of no more than 20 mm. It can be recognised by the following characters: head ; alt. 787 m; 1.vi.2015; leg. Peixin Cong; genitalia slide No. DNAYLL18124. Paratype: China: \u2022 1 \u2642; Hainan Province, Mt. Jianfeng; alt. 745 m; leg. Xia Bai; genitalia slide No. XMR18217.D.zinica , but can be separated from it by the male genitalia structures. In D.auriformis sp. nov., the left valva is narrowed and clavate, the right valva is bilobate, the bullet-like sternum VIII is smooth in the male genitalia, whereas in D.zinica, the left valva is broad, the right valva is not divided and the sternum VIII bears long and thin bristles on outer margin.The new species is externally similar to Adult .auriformis, meaning ear-shaped, referring to the ear-shaped uncus lobes.The specific name is derived from the Latin MZ711361/ DRYAD001-21. Dryadaulaauriformis sp. nov. is clearly distinguishable by its DNA barcode from its congeners, the minimum divergence ; alt. 1250 m; 23.v.2011; leg. Linlin Yang & Yinghui Mou; genitalia slide No. YLL11112.Dryadaulaflavostriata sp. nov. is similar to D.caucasica , but differs from it by the forewing peppered with more ochreous yellow scales that form stripes between fold and dorsum; the male genitalia with short uncus that is equipped with a rectangular process at the left and the sub-oval left valva with processes of different shapes, not bearing thorns or long bristles. In D.caucasica, the forewing has dark grey-brown longitudinal stripes between fold and dorsum; in the male genitalia, the elongate uncus has no process and the fluted left valva has dense, long bristles along outer ventral margin and a globular sclerotisation which is densely thorned.Adult .flav-, meaning yellowish and the Latin word striatus, stripe, referring to the forewing with inwardly oblique ochreous yellow stripes between fold and dorsum.The specific name is derived from the Latin prefix Taxon classificationAnimaliaLepidopteraTineidae\ufeff6E709E13-5D64-5D76-AD2E-454A7140D977http://zoobank.org/3BC5ADCC-97DA-4685-B9C4-39D6C013B943Holotype: China: \u2022 \u2642; Guangxi Province, Nanning City, Mt. Daming ; alt. 1250 m; 23.v.2011; leg. Linlin Yang & Yinghui Mou; genitalia slide No. YLL13026. Paratypes: China: \u2022 1 \u2642; Zhejiang Province, Jingning She Autonomous County, Wangdongyang Wetland Reserve ; alt. 1174 m; 16.viii.2018; leg. Shuai Yu et al.; genitalia slide No. DNAYLL18170 \u2022 1 \u2642; Zhejiang Province, Jiangshan City, Mt. Xianxia, Shuangxikou Town, Laofoyan Village ; alt. 400 m; 26.v.2017; leg. Shuonan Qian and Jiaen Li; genitalia slide No. DNAYLL18169.D.irinae , but differs from it by the shape of valva in the male genitalia: in D.hirtiglobosa sp. nov., the left valva has a blade-shaped setose lobe apically and a sword hilt-like process subapically on ventral margin and the right valva is bilobate; in D.irinae, the left valva is divided into two parts, without blade-shaped setose lobe or sword hilt-like process, the right valva is not bilobate.The new species is externally close to Adult .hirt-, from hirtus meaning hairy and the Latin word globosus, globular, referring to the vinculum equipped with a globular lobe bearing long hairs.The specific name is derived from the Latin prefix MZ711362/ DRYAD002-21. The minimum divergence ; alt. 787 m; 5.iii.2016; leg. Qingyun Wang. Paratypes: China: \u2022 8\u2642, 1\u2640; same data as holotype, except dated 4\u20138.iii.2016; genitalia slide Nos DNAYLL18121m, DNAYLL18122m, DNAYLL18172, DNAYLL18173, XMR18158, XMR18334, XMR18335 \u2022 1\u2642; Hainan Province, Mt. Jianfeng; alt. 770 m; 29.v.2015; leg. Peixin Cong; genitalia slide No. DNAYLL18171 \u2022 2\u2640; Hainan Province, Mt. Jianfeng, Fengminggu; alt. 954 m; 8.viii.2017; leg. Xia Bai; genitalia slide Nos DNAYLL18123, XMR18241.D.trapezoides , but the flagellum has three cinereous bands towards apex, the forewing has an obscure blackish stripe at middle of fold and the ostium bursae located at middle on anterior 1/3 of sternum VIII in the female genitalia. In D.trapezoides, the flagellum has two dark fuscous bands towards apex, the forewing has pale yellowish spots suffused with a few dark scales above fold at 1/3 and 3/5 and the ostium bursae opens at left of sternum VIII in the female genitalia.The new species resembles Adult .securiformis, referring to the battle-axe-shaped left valva.The specific name is derived from the Latin word MZ711363/ DRYAD003-21 and MZ711364/ DRYAD004-21. The minimum distance (Table D.hirtiglobosa sp. nov., is 6.06%.DNA sequencing resulted in a barcode of 604 bp from two paratypes: Until this study, a total of 49 species have been described worldwide as identified in the checklist in Table"} +{"text": "Dear Editor,In our publication we stateThis statement is erroneous. Recently, it was pointed out to us that the Royal College of Obstetricians and Gynecologists of Canada Objectives of Training in the Specialty of Obstetrics and Gynecology were amended and include the following statement applicable after July 1, 2016:\u201cThe following procedures in List A are those that the fully trained resident in Obstetrics and Gynecology must be competent to perform independently: 5.2.2.41. Limited cystoscopy\u201dWe regret our error and apologise for any inconvenience.E-mail: gjacob2010@gmail.comG.P. Jacob, G.A. Vilos, F. Al Turki, G. Bhangav, B. Abu-Rafea, AG.. Vilos, A. Ternamian"} +{"text": "Scientific Reports 10.1038/s41598-020-78555-0, published online 09 December 2020Correction to: The original version of this Article contained a typographical error in the spelling of the author Jaime San-Miguel, which was incorrectly given as Jaime San Miguel Navas. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.Furthermore, the Author Contributions section now reads:\u201cSh.P. did the transcriptomic, evolutionary and over all data analysis and gave inputs for writing the manuscript. R.N. did the initial transcriptomic and proteogenomic analysis. J.S.-M. did the time-calibration analysis. R.C. did the proteomics experiments. T.W. did the initial quantitative transcriptomic analysis. M.T.W. did the initial transcriptomic analysis. Y.U. participated in the proteogenomics analysis. G.V. and E.A.M. generated the ON and PN liver transcriptomic datasets. S.P. designed and supervised the project, analysed the data, and wrote the manuscript.\u201d"} +{"text": "An infrared thermometer was first used to assess drought and heat tolerance in plant breeding more than 40 years ago. Soon afterward, this method became widely used throughout the world. However, Russia has not yet applied the described method for evaluating stress tolerance. This paper presents an overview of using infrared thermometry in plant breeding. Taking wheat as an example, it shows major advantages and disadvantages of canopy temperature depression (CTD) values measured by the infrared thermometer. The paper also demonstrates that genotypes with higher CTD values, and therefore with a lower canopy temperature, use more available soil moisture under drought stress to cool the canopy by transpiration. It refers to CTD as an integrative trait that reflects an overall plant water status. Its coefficient of variation lies in the interval of 10 to 43 %. A large number of publications illustrate a close relation between CTD values and yield and indicate a high heritability of the former. Meanwhile, the same works show that yield has a higher heritability. Moreover, some researchers doubt that CTD should be used in applied wheat breeding as there are many factors that influence it. CTD has a high correlation with other traits that reflect plant water status or their adaptation to drought or heat stress. Quantitative trait loci (QTLs) associated with CTD are localized in all chromosomes, except for 3D. These QTLs often explain a small part of phenotypic variance , which complicates the pyramiding of canopy temperature genes through marker-assisted selection. The paper concludes that the evaluation of CTD appearsto be a reliable, relatively simple, labor-saving, objective, and non-invasive method that sets it apart from othermethods as well as shows the best results under terminal drought and heat stress conditions Every year 200 million hectares of wheat (Triticum aestivumL.) cultivated worldwide suffer economic losses fromdrought and heat for wheat is very sensitiveto heat stress. Optimal temperature for photosynthesis inwheat is approximately 25 \u00b0C . It hasbeen estimated that 1 \u00b0C increase above the optimal temperatureat the grain filling stage decreases wheat yield by 3\u20134 %.Breeding drought-tolerant cultivars is one of the possibleways to reduce damage from drought. However, it requiresmuch time and effort as it includes the evaluation of a largenumber of plants and is complicated by a low and inconsistentcorrelation between the phenotype and the yield underdrought conditions, with multiple mechanisms of adaptationbeing involved. The selection that is based solely on yieldindicators complicates breeding for drought tolerance becausethe yield shows low heritability under drought stress . With that in mind, to evaluate many genotypes ina short period of time, it is important to single out other traitsassociated with drought tolerance .The paper suggests several physiological traits to identifytolerant genotypes. It refers to physiological traits as traits thatcontribute to mechanisms playing a role in plant adaptationto stress , such as coleoptile length,ability to stay green, stem water soluble carbohydrate, leafwater potential, canopy temperature, and so on.This paper presents an overview of using infrared thermometryin plant breeding.Canopy temperature is an integrative trait that reflects theplant water status or the resultant equilibrium between theroot water uptake and shoot transpiration .Under the high solar radiation and drought conditions, stomatalconductance decreases, soil moisture deficit reduces normaltranspiration rate, which in turn increases canopy temperature. Thus, canopy temperature can be usedto study drought and heat tolerance in plants. Instead of canopytemperature, researchers often calculate canopy temperaturedepression (CTD) that refers to a metric, indicating the differencebetween air temperature and canopy temperature. If the canopy temperature is lower thanthe air temperature under the influence of transpiration, thenCTD is expressed as a positive value, but becomes negativeif the reverse is true. Genotypes with higher CTD values anda cooler canopy temperature under drought stress use moreavailable soil moisture to cool the canopy by transpiration.Given that Russian research lacks an established definitionfor \u2018canopy temperature depression\u2019, the paper refers to it asCTD defined in English research.Canopy temperature is measured by a handheld infraredthermometer or thermal camera . It isdone in the afternoon in clear weather conditions on windlessdays. The most considerable genotypic differences in CTD arereported from 2 to 3 p. m. at high temperaturesand low relative humidity . Theresearcher should stay close to the plot not to cast shadow onthe place of measurement . If a plot is sownin rows, it is best to stand to one side of it so that the infraredthermometer is pointed at an angle to the rows. If groundcover is low, it is best to point the thermometer at a low angleto the horizontal to minimize the likelihood of viewing soil. The infrared thermometer is held atapproximately 50 cm above the canopy, and the measurementsare taken at 1 m from the edge of the plot . The best phase to perform measurementsis the grain filling period .The infrared thermometer was first used for scheduling cropirrigation in the 1970s and for studyingdrought tolerance in the 1980s . In late1980s, CIMMYT began to use CTD measurements as selectioncriteria in breeding for drought and heat tolerance in variousexperiments. Bulks showing high CTD values are selectedin F3 generation . Canopy temperature measurementscan significantly improve the selection of droughttolerant genotypes because of their high speed (\u224810 secondsper plot), simplicity, and relative economic efficiency. CTDis also integrative of the whole canopy due to scoring manyplants at once, thus reducing error associated with plant-toplantvariation .However, this method has some limitations. First, the measuringaccuracy depends on microclimate of the plant stand. Second,rapid changes in environmental conditions, for exampleon cloudy days, demonstrate high variability of the results. Third, CTD is influenced by many biologicaland environmental factors, such as air temperature and relativehumidity, soil moisture, wind, solar radiation, evapotranspiration,leaf adjustment to water deficit , plantdensity , spike size, color and size of leaves, angle of leaves ,peduncle length and awns . Finally, plantorgans differ in their self-cooling abilities, and thus, canopytemperature with spikes is 2 \u00b0C higher than the one withoutthem .The fact that these limitations have already been identifiedallows us to conclude that CTD and its features are well researched.Some environmental flux during the measurementperiod is inevitable, but correcting data against reference plots, use of replication, and repetition of data collection during thecrop cycle can compensate for this .CTD values demonstrate a significant correlation with yieldunder drought and heat stress in a large number of experiments. Theyhave regression relationships: if CTD decreases by 1 \u00b0C, theyield declines by 1.5 and 1.7 q/ha . In thisregard, the trait should be considered as a significant selectioncriterion in breeding programs not only in Mexico, but also inother countries of the world . Newer cultivars of wheat have cooler canopy, although the cultivars that are releasedin different decades under favorable growing conditions orirrigation do not show this correlation .Various studies identify high correlation between CTD andother traits that reflect plant water status or their adaptationto drought or heat, including stomatal conductance , delay in the senescence of leaves , leaf and stem wax , depth anddistribution of root system in soil ,spike sterility , and 1000 grain weight.The coefficient of variation of CTD in different studies rangesfrom middle ) to high ). Dryland conditions make CTD values negative and increase genotypic differences . In this respect, CTD value appears to be a betterparameter for drought tolerance than yield under droughtstress. Some research suggests that canopy temperaturehas a larger genetic value \u2013 if compared to direct selectionbased on yield and other traits \u2013 as it is an indirect index tothe selection of certain types of cultivars and shows higherheritability and genetic correlation with yield . Althoughsome studies put CTD heritability at0.65\u20130.80 , there is avast amount of research that calculates heritability for bothCTD and yield and concludes that the latter has the largerheritability (see the Table).One of the possible reasons for the low heritability of CTDvalue is environmental influence . Thus,literature review demonstrates that CTD cannot be referredto as the better selection criteria if compared to yield criteriaunder drought stress. This indicator is better used as an additionalparameter in measuring drought tolerance in cultivars.CTD genetic control has been extensively studied during thelast two decades. For example, in their study, Acu\u00f1a-Galindoet al. (2015) analyzed 30 pieces of research from 2002 to 2011and identified four meta-QTLs (MQTLs) containing two ormore QTLs for the trait that were associated with droughtand heat tolerance, including CTD value that was identifiedin independent studies, populations, or environments. TheseMQTLs were localized on chromosomes 1B (34 \u00b1 2 \u0441\u041c),2B (68 \u00b1 2 \u0441\u041c), 3B (139 \u00b1 4 \u0441\u041c), and 7A (100 \u00b1 6 \u0441\u041c). Theresearch also described single QTLs for CTD: these MQTLswere localized on chromosomes 3B, 4A, 7A, while chromosome5A contained three MQTLs. QTLs associated with CTDwere co-localized with QTLs that controlled other adaptivetraits . Whilesummarizing the results of their and prior research, Pinto etal. (2010) suggested that QTLs for canopy temperature werelocalized on chromosomes 1A, 1B, 1D, 2A, 2B, 3A, 3B, 4A,4B, 5A, 5B, 6A, 6B, 6D, 7A, and 7B. The research undertakenafter 2011 discovered QTLs for CTD on almost all chromosomes,except for 1D, 3A, 3D, and 6D .Some research showed that QTLs associated with CTDwere co-localized or closely localized with genes Rht-B1, Rht-D1 (semi-dwarf wheat with warmercanopy), Ppd-D1 , Vrn-A1 , and transcription factor Dreb1 .These loci for canopy temperature are responsible for 10\u201320 % of the phenotypic variation or even less than 10 %, and this isunderstandable as CTD is an integrative trait that is correlatedto many mechanisms of drought tolerance .Moreover, canopy cooling at different stages is controlled byloci with different localization ; therefore, the result of CTD measurements depends onthe plant growth stage . It is likely thatthe small genetic effects of multiple QTLs combined with thesmaller population sizes commonly used in breeding will limitthe pyramiding of multiple alleles for CTD through markerassistedselection .CTD indicates any kind of stress: high temperature, wateror nutrient shortage . Nitrogen fertilizersincrease CTD values . Thus, this parametershows not only water, but also a nitrogen nutrient status ofplants . CTD is also related to NDVI , and canopy temperature may increase due toZymoseptoria tritici infection . At thesame time, high canopy temperatures provide unfavorableconditions for the development of stripe rust . As the environmental factors have the aggregate effecton plants, CTD measurements that are performed for screeningof drought tolerance without drought stress may produceincorrect results.In addition to the well-studied negative correlation betweenyield and CTD values under drought or heat stress, theresearchers highlight the controversy of their relationships invarious environments . For example, ina high-yielding environment, cultivars with relatively highCTD values tend to produce higher yields than those withlow CTD values, while in a low-yielding environment, therelationship between these traits disappears .However, it is explained by the fact that differences in planttolerance become noticeable only if limiting factors are intense. Some studies show insignificant orpositive correlation between CTD and yield , while others identify that underdrought stress, high-yielding genotypes have both positiveand negative CTD values .The research shows that a relatively large proportion ofyield phenotypic variation under drought stress can be explainedby a small number of traits, including CTD values.In most cases, they would be amenable to reliable quantificationin parents and verification of expression in segregatingprogeny . However, it was impossibleto accurately measure CTD values in some research becausethe plant canopy failed to cover the ground or the yield was highly dependent on limited amounts of soilstoredwater . Thus, Balota et al. (2017)identified the difficulty of using CTD values in applied plantbreeding, for in that work a potential effect of neighbor plotsplant height on canopy temperature was present.More than that, a certain amount of caution is advisable inselecting genotypes with high CTD values in water-limitedenvironments as more vigorous, later-flowering wheats mayproduce more biomass by the time canopy temperature ismeasured. Biomass and transpiration are physiologicallylinked, so that higher-biomass lines seem to deplete soilwater faster, causing stomata to close and canopies to warm.Selection of cooler canopy temperature under conditions ofsoil-water depletion could favor the development of lines withlow yield potential and smaller biomass or identification of specific genotypes . a non-invasive method, and this sets it apart from others. Tobetter evaluate cultivars tolerance to drought or heat stress,a substantial number of traits should be considered, thereforemaking CTD a meaningful contribution to knowledgeon drought tolerance. Still, it is important to realize that thismethod shows the best results under terminal drought andheat stress conditions.All things considered, the paper suggests that in general theevaluation of CTD appears to be a reliable, relatively simple,labor saving, and objective method that may be used to assessplant tolerance to heat or drought stress. Moreover, it isa non-invasive method, and this sets it apart from others. Tobetter evaluate cultivars tolerance to drought or heat stress,a substantial number of traits should be considered, thereforemaking CTD a meaningful contribution to knowledgeon drought tolerance. 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Technol. 2018;156(1):13-23. DOI10.1017/S0021859617000946Yousfi S., Gracia-Romero A., Kellas N., Kaddour M., Chadouli A., KarrouM., Araus J.L., Serret M.D. Combined use of low-cost remotesensing techniques and \u03b413C to assess bread wheat grain yield underdifferent water and nitrogen conditions. Agronomy. 2019;9(6):285.DOI 10.3390/agronomy9060285Zhang X., Zhang X., Chen S., Sun H., Shao L., Liu X. Optimized timingof using canopy temperature to select high-yielding cultivars ofwinter wheat under different water regimes. Exp. Agric. 2018;54(2):257-272. DOI 10.1017/S0014479716000235Zhang Y., Zhang Y., Wang Z., Wang Z. Characteristics of canopy structureand contributions of non-leaf organs to yield in winter wheatunder different irrigated conditions. Field Crops Res. 2011;123(3):187-195. DOI 10.1016/j.fcr.2011.04.014."} +{"text": "They are spiral-shaped and have flagella, which extend from motors at the pole, producing undulating movement through fluids, enabling tissue invasion and dissemination (Treponema pallidum subsp. pallidum as Spirochaeta pallida from a fresh human vulvar lesion.From the Greek mination . In 1905Treponema spp. can invade the epidermis and oral, intestinal, and genital mucosa of humans and animals. They cause human diseases, such as syphilis, yaws, pinta, and bejel, and animal diseases, such as digital dermatitis. T. phagedenis, T. pedis, and T. medium infect mainly cattle. T. paraluiscuniculi can cause syphilis in rabbits.Treponema spp. are not cultivable, except for T. palllidum subsp. pallidum and T. phagedenis. T. pallidum subsp. pallidum causative syphilis is a reemerging disease in industrialized countries. Digital dermatitis, a polytreponemal disease, is considered to be the major infectious claw disease in cattle worldwide.Most"} +{"text": "Individual behavioral differences are due to an interaction of the genotype and the environment. Phenotypic manifestation of aggressive behavior depends on the coordinated expression of gene ensembles. Nonetheless,the identification of these genes and of combinations of their mutual influence on expression remains a difficulttask. Using animal models of aggressive behavior , we evaluated the expression of 10 genes potentially associated with aggressiveness accordingto the literature: Cacna1b, Cacna2d3, Drd2, Egr1, Gad2, Gria2, Mapk1, Nos1, Pomc, and Syn1. To identify the genes mostimportant for the manifestation of aggressiveness, we analyzed the expression of these genes in two generations ofrats: 88th and 90th. Assessment of gene expression levels was carried out by real-time PCR in the hypothalamus oftame and aggressive rats. This analysis confirmed that 4 out of the 10 genes differ in expression levels between aggressive rats and tame rats in both generations. Specifically, it was shown that the expression of the Cacna1b, Drd2,Egr1, and Gad2 genes does not differ between the two generations (88th vs 90th) within each strain, but significantlydiffers between the strains: in the tame rats of both generations, the expression levels of these genes are significantlylower as compared to those in the aggressive rats. Therefore, these genes hold promise for further studies on behavioral characteristics. Thus, we confirmed polygenic causes of phenotypic manifestation of aggressive reactions. Behavioral patterns in individuals of the same species are dueto the interaction of a genotype and social experience . At the same time, it is difficult toidentify genes associated with a specific behavior type andcombinations of their mutual influence on each other. Studieson aggressive behavior and its genetic causation require experiments on modelanimals that differ in some aggressiveness parameter, so thatit is possible to adequately assess the phenotypic manifestations of aggressiveness under the conditions that are set upand controlled by researchers . Experimental studies on modelanimals will make it possible to identify orthologous genesassociated with aggressive behavior in different species; thesedata are necessary for subsequent identification of evolutionary patterns in how aggressiveness is determined by geneticfactors in animals.It is known that the level of aggressiveness is inherited; genetic control of the phenotypic variation in the aggressivenesslevel in animal populations has been confirmed experimentally. Most of such studiesare focused on one specific gene out of those associated withaggressive behavior, for example, studies on the differentialexpression of genes of the estrogen receptor ,serotonin receptor , dopamine receptor , Maoa, genes Bdnf andNos1 , and other well-known genes associated with aggressiveness.On the other hand, many reviews on the genetics of aggressive behavior indicate polygenic causes of aggressive behaviorin animals, i. e., phenotypic manifestation of individual aggressive reactions is controlled by simultaneous expressionof many genes, namely, whole ensembles of genes .In rats of tame and aggressive strains, the expression ofgene groups in cerebral hemispheres of males and femaleshas been investigated , but there are somedifficulties with correct interpretation of the results becausethere are known effect of the ovulation cycle on all physiological processes of the female body. In another work, differentially expressed genes were revealed in hybrid animals of the2nd generation, obtained by crossing tame and aggressive rats. Undoubtedly, cerebral hemispheres playa leading role in the implementation of higher brain functions.Nonetheless, genetic control of aggressive behavioral reactions is primarily carried out by the hypothalamus: the centralbrain structure that controls emotions. Studies have shownthat electrical stimulation of some areas of the hypothalamusleads to the manifestation of aggressive behavior .Therefore, in our work, we analyzed expression levels of10 genes in the hypothalamus, those that, according to theliterature, are associated with aggressive behavior. For thispurpose, we used model animals, rats, while tracing the stability of gene expression in two generations of the studied rats.Namely, we used males of two outbred strains of gray rats(Rattus norvegicus). The rats had been selected for elimination (tame or domesticated) and enhancement of aggressivedefensive reaction to humans . In response tothe presentation of the stimulus, i. e., a researcher\u2019s hand ina thick glove , the ratsof the tame strain reacted calmly, i. e., approached and sniffedthe glove without performing any aggressive actions; on thecontrary, the rats of the aggressive strain reacted violentlyby immediately attacking the stimulus. Tame and aggressiverats were taken from 88th and 90th generations of breeding.Studies of the tame and aggressive rats after 60\u201370 generations have shown differences in some behavioral reactions inthe open field test, Morris water maze test, and elevated plusmaze test as well as differences in morphometric parametersof the cranium and changes in fur coloration .Expression levels of 10 genes were analyzed: Cacna1b and Cacna2d3 encode subunits of highthreshold calcium channels that release neurotransmitters.Calcium channels play a critical part in the manifestation ofaggressive behavior through synaptic transmission of neurotransmitters GABA and serotonin .The Drd2 gene (dopamine receptor D2) is the gene for dopamine receptor D2, which is involved in the processes ofmotivation and learning; changes in the expression of theDrd2 gene cause various pathologies, including increasedaggressiveness .The Egr1 gene (early growth response 1) encodes a proteinthat activates the transcription of genes participating incell division and differentiation. Egr1 is a transcriptionfactor that regulates the expression of several genes thatare associated with long-term memory . It is known that Egr1 expression increasesin response to stress , and, in addition, Egr1 knockout male micedo not demonstrate aggressive behavior in the presenceof other males .The Gad2 gene (glutamate decarboxylase 2) encodesglutamate decarboxylase, which catalyzes the conversionof glutamate to GABA , and thus the Gad2 genetakes part in the control of the emotional state of experimental animals, by regulating social, including aggressive,behavior . In particular, it has beenreported that Gad2 knockout mice have lower levels ofaggressive-behavior indicatorsThe Gria2 gene (glutamate ionotropic receptor AMPAtype subunit 2) encodes a subunit of glutamate receptor:the most important participant of excitatory processes inthe central nervous system. Blockage of this receptor innaive mice decreases aggressiveness in comparison withlittermates having normally functioning glutamate receptors .The Mapk1 gene (mitogen-activated protein kinase 1) encodes a mitogen-activated protein kinase, which performsa complex function in cellular processes incentral-nervous-system neurons. It was demonstratedthat mice with a conditional knockout of this gene exhibitincreased aggressiveness .The Nos1 gene (nitric oxide synthase 1) encodes an enzyme, neuronal nitric oxide synthase, that catalyzes thesynthesis of nitric oxide and is an important player inneurotransmission. Studies have shown that the roleof the Nos1 gene in aggressive behavior is based onthe interaction of nitric oxide synthase with serotonintransporter, and this process decreases serotonin uptake and leads to a decrease in aggressiveness .The Pomc gene (proopiomelanocortin) is a gene ofa prohormone, proopiomelanocortin, which is a precursorof adrenocorticotropic hormone. Studies have revealedthat melanocortin is associated with aggressive behavior. In particular, in aggressive foxes,the level of expression of the Pomc gene is lower ascompared to tame foxes .The Syn1 gene (synapsin I) encodes a phosphoproteinthat regulates the release of neurotransmitters in synapseson the surface of synaptic vesicles. Research on ratsand mice indicates a decrease in the expression of Syn1during chronic stress and early isolation , which is usually accompaniedby changes of behavior in general and aggressivenessin particular.Experimental animals. The number of experimental rats wasdetermined and experiments on the rats were carried out inaccordance with international European bioethical standards(Directive 2010/63/EU) and the Guidelines for the Care andUse of Laboratory Animals approved by the Ministry of Healthof Russia .The work was performed on sexually mature males of the88th and 90th generations of two outbred strains (tame andaggressive). The experiment involved 6 animals ofthe 88th generation (3 tame rats vs. 3 aggressive rats) and 12 animalsfrom the 90th generation (6 tame rats vs. 6 aggressive rats).To exclude the influence of the photoperiod on the physiologyand behavior of the experimental animals, we used rats bornat the same time of the year. In accordance with the selectioncriterion , the aggressive-defensiveresponse in selected aggressive rats corresponded to a scoreof \u20133.5 points. For tame rats, the behavioral score in the glovetest was +3.5 points, which is an indicator of strong domestication.Isolation of total RNA and real-time PCR (RT-PCR).Hypothalamic samples were dissected postmortem, collected into liquid nitrogen, and stored at \u201370 \u00b0C until use.Total RNA was extracted from frozen tissue specimens usingthe TRIzol\u2122 Reagent according to themanufacturer\u2019s protocol. RNA quality was evaluated on anInvitrogen Qubit\u2122 2.0 fluorometer . The RNA was purified using paramagneticRNAClean XP beads and dissolvedin double-distilled water. To remove impurities of genomicDNA, the RNA was treated with DNase I . RNA quality was determined on AgilentBioanalyzer 2100 .Complementary DNA (cDNA) was synthesized with kitsfrom Syntol (Russia). The reaction included 1 \u03bcg of RNA, andall the procedures were carried out according to the manufacturer\u2019s protocols. Oligonucleotide primers for RT-PCR weredesigned in the PrimerBLAST software (see the Table). Geneexpression was assessed by RT-PCR using the CFX96 RealTime PCR Detection System . After the PCR,for reactions with the intercalating dye EVAGreen, productspecificity was assessed by melting-curve analysis. Eachreaction was carried out in duplicate .Amplification efficiency was 90 to 110 % for each primer pair.Target genes\u2019 expression values were normalized to Rpl30expression as a reference.Statistical analysis. This analysis of the PCR results wasperformed by Student\u2019s t test as well as factor analysis . The statistical analyses wereperformed in Statistica 6.0. Results are presented as mean \u00b1standard error of the mean, and data satisfying the conditionp < 0.05 were considered statistically significant.By RT-PCR verification in the hypothalamus of 88th generation rats, genes were identified that were differentially expressed between the aggressive strain and tame strain of rats.Thus, in aggressive rats, expression levels of genes Cacna1b,Cacna2d3, Drd2, Egr1, Gad2, Gria2, Mapk1, and Syn1 werefound to be significantly higher as compared to tame rats. The expression of genes Nos1 andPomc did not differ significantly between tame and aggressiverats of the 88th generation of the selection for the reaction tohumansThe expression of genes Cacna1b, Drd2, Egr1, and Gad2in the hypothalamus turned out to be significantly higher inaggressive 90th generation rats than in tame rats of the samegeneration . On the contrary, in theseanimals, no significant interstrain differences were foundin the expression of genes Cacna2d3, Gria2, Mapk1, Nos1,Pomc, and Syn1.In the assay of mRNA levels of the same genes in the hypothalamic samples from rats of the 88th and 90th generations,it was found that the expression of Cacna1b, Drd2, Egr1, andGad2 is significantly lower in rats of the tame strain than in theaggressive strain, regardless of the generation. Therefore, thesegenes hold promise for further research as genes determiningthe behavioral phenotype of rats during the selection for thereaction to humans.Additionally, in the factor analysis of the pooled data ongene expression in animals of the 88th and 90th generations,only two significant factors were identified . The firstfactor significantly correlates withthe expression of 4 genes and explains the percentage of variance (32 %) inthe experimental data that corresponds to the difference between aggressive and tame rats. The second factor significantlycorrelates with the expression of 3 other genes and indicatesintragroup variance (31 %) common between the aggressiveand tame animals. The third factor accounts for 12 % of thevariance but does not significantly correlate with the expression of any analyzed genes (data not shown).Here, in our analysis of RT-PCR data, between tame andaggressive rats (two generations: 88th and 90th generationsof rats selected for a reaction to humans), we identified 4 differentially expressed genes out of the 10 studied. Meanwhile, it was found that mRNAlevels of these genes do not differ between the two generationswithin each strain.The Cacna1b gene encodes the Cav2.2 protein, which isa subunit of high-threshold calcium channels that control therelease of neurotransmitters from neurons. This subunit of the calcium channel regulates the passage of calcium ions, therebydetermining the properties of the channel. The Cacna1b geneis expressed weakly in the brain , butthe calcium channel subunit encoded by it plays an importantrole in the body\u2019s response to aversive stimuli . Calcium channels promote a release of neurotransmitters at excitatory synapses, resulting in suppression ofexploratory behavior on the one hand and novelty-inducedanxiety-like behavior on the other.Nevertheless, as demonstrated in the 74th generation of ratsselected for a reaction to humans, the exploratory behavior inthe open field test is practically the same between tame andaggressive rats . Accordingly, thehigher expression of Cacna1b in aggressive rats than in tamerats is probably associated with differences in anxiety-likebehavior under novel conditions, as confirmed by the workof Kozhemyakina et al. (2016). In particular, in rats selectedfor increased aggressiveness, total motor activity for 5 minof the behavioral test is significantly higher; this parameterreflects the level of anxiety.Our results somewhat contradict a study conducted onknockout mice, where it was shown that in the absence ofcalcium channel subunits, the aggressiveness of experimentalanimals is significantly higher . This discrepancy can be explained by the fact that the functioning ofcalcium channels is not directly related to aggressive reactionsof the animal but rather is related to these reactions indirectlythrough a release of neurotransmitters, which, depending onthe action of the neurotransmitter, determines the behavioralresponses of the animal. For instance, serotonin, according tonumerous studies, affects aggressiveness , whereas the data on the correlation betweenserotonin levels and aggression are contradictory. Achronic and sustained serotonin release ispositively associated with both normal aggression and with the pathologicalaggression characteristic of psychiatric patients . Thus, our study supplements the international researchdata on the relation between the expression of Cacna1b and aggressive behavior.The expression of the Drd2 gene (dopamine D2 receptor) isassociated with aggressive behavior, as uncovered in studieson rats and on humans . Given that dopamine (an endogenous ligand [agonist]of D2 receptor), just as serotonin, is involved in the regulationof aggressive behavior, a change in Drd2 expression leads tovarious pathologies, for example, to increased aggressiveness. At the same time, an aggressiveinteraction stimulates dopaminergic and serotonergic activitiesin the limbic regions of the brain .In other words, hypothalamic-neuron activation, leading to therelease of dopamine, may in turn promote the excitation ofthose hypothalamic neurons that control the attack . In relation to our study, these literature dataindicate that the increased level of Drd2 expression in aggressive rats of both generations may actually be related to thephenotypic manifestation of aggressive reactions to humans.The third differentially expressed gene in the rats selectedfor the reaction to humans, Egr1, encodes a transcription factorparticipating in the transcriptional activation of genes necessary for mitogenesis and cell differentiation. It is known thattranscription factor Egr1 regulates the expression of genes thatcontrol synaptic plasticity and learning and memory processes;these functions make Egr1 an important object of research onthe coherence of neural responses to various stimuli . It has been reported that after exposure tostress, the expression of Egr1 in rats increases in neocorticalregions, including the hypothalamus .The higher expression of the Egr1 gene that we found inaggressive rats compared to tame rats can apparently be explained by the response to the stimulus that was employed for the artificial selection;in essence, this is a response to a stressor. Probably, in ratsof the aggressive strain, the perception of the stimulus at themolecular level affects mechanisms of the genetic response tostress, in contrast to rats of the tame strain, which, as describedabove, react quite calmly not only to a human hand under thetest conditions but also in general. Differential expression ofEgr1 between the rats with genetically acquired aggressiveor nonaggressive behavior toward humans is, in our opinion,an interesting result that can be applied to further research.Gad2 is another gene for which we demonstrated differential expression between tame and aggressive rats of both generations. This gene encodes glutamate decarboxylase (GAD),which catalyzes the conversion of glutamate to GABA, aneurotransmitter that inhibits neuronal impulses. It is knownthat GABA controls aggressive behavior . Studies on mice have shown thataggressive animals have lower GABA levels due to decreasedGAD activity in several regions of the brain as compared to nonaggressive animals . On the other hand, these data were notconfirmed in a study on Gad2 knockout mice, which havea reduced amount of GABA in the brain during postnataldevelopment; however, such mutant males manifest reducedaggressiveness in the resident\u2013intruder test .The effect of GABA depends on the area of the brain, the typeof receptors, and the specific context of the situation causingthe aggressive behavior . In ourwork, the higher level of Gad2 expression in aggressive ratsthan in tame rats most likely corresponds to a situation when anincrease in GABA synthesis in hypothalamic neurons causesan aggressive reaction of the animals in the \u201cglove test,\u201d whichwas employed for the artificial selection.Furthermore, the factor analysis when the data on geneexpression in the 88th and 90th generations were combinedallows us to conclude that the following. Although the artificialselection was carried out by means of two vectors \u2013 (1) fromthe wild type to aggressive behavior and (2) from wild typeto tame behavior \u2013 the expression of the 10 studied genesis associated with two factors: the difference between tameand aggressive rats andsome general change that is the same for these two groups of animals . Meanwhile, the \u201cdomestication\u201dfactor is common between the rats of both generations butclearly distinguishes the animals by behavioral phenotype:tame or aggressive behavior . This result enablesus to conclude that, indeed, the increased expression of genesCacna1b, Drd2, Egr1, and Gad2 determines aggressive behavior in the selected rats, while the decreased expressioncorresponds to tameness.Thus, genes Cacna1b, Drd2, Egr1, and Gad2, for whichwe showed interstrain differential expression in both generations (88th and 90th) of the rats selected for the reaction tohumans, are promising for further studies on characteristicsof domestication and aggressive behavior in animals. In ourwork, it was revealed that the manifestation of an aggressiveand nonaggressive reaction to humans in rats of the 88thand 90th generations iscontrolled not by one but by several genes. 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Trophic redundancy and predator size class structure drive differences in kelp forest ecosystem dynamics."} +{"text": "Psychol. Manage. J. 21, 130\u2013150. doi: 10.1037/mgr0000070In the original article, the reference for Castiello D'Antonio was incoPsychol. Manage. J. 21, 130\u2013150. doi: 10.1037/mgr0000070It should be Castiello D'Antonio, A. (2018). Coaching psychology and positive psychology in work and organizational psychology. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "In this review, we discuss the progress in the study and modification of subtilisin proteases. Despite longstanding applications of microbial proteases and a large number of research papers, the search for new proteasegenes, the construction of producer strains, and the development of methods for their practical application are stillrelevant and important, judging by the number of citations of the research articles on proteases and their microbialproducers. This enzyme class represents the largest share of the industrial production of proteins worldwide. Thissituation can explain the high level of interest in these enzymes and points to the high importance of designing domestic technologies for their manufacture. The review covers subtilisin classification, the history of their discovery,and subsequent research on the optimization of their properties. An overview of the classes of subtilisin proteasesand related enzymes is provided too. There is a discussion about the problems with the search for (and selection of)subtilases from natural strains of various microorganisms, approaches to (and specifics of) their modification, aswell as the relevant genetic engineering techniques. Details are provided on the methods for expression optimization of industrial subtilases of various strains: the details of the most important parameters of cultivation, i.e., composition of the media, culture duration, and the influence of temperature and pH. Also presented are the resultsof the latest studies on cultivation techniques: submerged and solid-state fermentation. From the literature datareviewed, we can conclude that native enzymes currently hardly haveany practical applications because of the decisive advantages of the enzymes modified by genetic engineering andhaving better properties: e.g., thermal stability, general resistance to detergents and specific resistance to variousoxidants, high activity in various temperature ranges, independence from metal ions, and stability in the absenceof calcium. The vast majority of subtilisin proteases are expressed in producer strains belonging to different speciesof the genus Bacillus. Meanwhile, there is an effort to adapt the expression of these enzymes to other microbes, inparticular species of the yeast Pichia pastoris. Proteases are enzymes that degrade proteins via the hydrolysisof peptide bonds. Proteases correspond to the general enzymeclass designated as EC 3.4.X.X . Endopeptidases act most strongly on intact proteins;they cleave peptide bonds of nonterminal amino acid residues.Exopeptidases sever peptide bonds between amino acid residues at the end of a polypeptide chain. They are categorizedinto amino- and carboxy-peptidases depending on which end(N- or C-terminus) they remove amino acids from . Proteases are subdivided into families inaccordance with their mechanism of action. According todatabase MEROPS (http://merops.sanger.ac.uk) , the following protease families are known: asparagine, cysteine, glutamine, serine and threonine peptidases,metalloproteinases, mixed peptidases, and peptidases with anunknown mechanism of actionPeptidases are present in all life forms. Today, the mostpopular proteases are those from prokaryotes, mainly bacteria, because of their excellent potential for various technological applications. Given that proteases are needed in largeamounts, the cost of production is as important as proteasecharacteristics; as a consequence, in most cases, proteasesare manufactured by means of bacteria. Microorganisms canproduce proteases faster and more cheaply than mammalianand plant cells can; the enzyme manufacture is not affectedby the climate or changes of seasons or by regulatory or ethical problems. Besides, extracellular enzymes expressed bymicroorganisms are usually preferred because subsequentprocessing is simpler, meaning even lower costs . In terms of a combination of characteristics,subtilisins or subtilases have turned out to be the most popularclass of proteases.Subtilases are one of the largest classes of serine proteasesthat are encoded in the genomes of all life forms includingviruses. By amino acid sequence, subtilases are subdividedinto six families: subtilisins, thermitases, proteinases K, lantibiotic peptidases, kexins, and pyrolisins. Subtilisins in turnare categorized into several subfamilies: true subtilisins, highly alkaline proteases, intracellular proteases, intermediatesubtilisins, and high-molecular-weight subtilisins.All the subfamilies of subtilisins hold promise for biotechnology. The first alkaline serine protease that gainedwidespread use was subtilisin A (EC 3.4.21.62), which is an alkaline serine protease from Bacillus subtilis. The enzymeowes its name to the species of its bacterial producer . The historyof discovery and study of subtilisins started at a researchcenter of a beer-brewing company called Carlsberg, and thefirst enzyme to be described is named \u201csubtilisin Carlsberg\u201d.The catalytic center of serine proteases is formed by threeamino acid residues: Asp-32, His-64, and Ser-221. Becausethe amino acid residue carrying out the nucleophilic attack isSer-221, subtilisins and the related proteolytic enzymes arecalled serine proteinases. Among the highly alkaline proteases,there is an enzyme isolated from strain Bacillus sp. KSM-K16. Its optimum of activity is at 55 \u00b0Cand pH 12.3. This enzyme is employed in the industry in complex with a detergent, as is the case for related highly alkalineproteases, Savinase and Maxacal. Intermediate subtilisinsare somewhere between true subtilisins and highly alkalineproteases and include some promising enzymes. For instance,the ALTP enzyme isolated from Alkaliphilus transvaalensis shows maximal activity at veryhigh temperatures and pH, namely, at 70 \u00b0C and pH>12.6.Nonetheless, ALTP can also perform a catalytic function atlower temperatures and pH. The phylogenetic tree based onthe amino acid sequences of subtilisin proteases is presentedin the Figure.Intracellular proteases are rather poorly studied in comparison with the above subfamilies. The reason is that they areactive at lower pH, which is characteristic of the cytoplasm.For example, the intracellular protease from B. megaterium at 50 \u00b0C shows an optimum of activityat pH 6.0\u20137.0.From alkalophilic Bacillus spp., researchers isolated a setof high-molecular-weight subtilisins ~650 amino acid residues long (size of the precursor: 800 aminoacid residues). Their optimal pH is 10.5\u201311.0, and optimaltemperatures for activity are 40\u201345 \u00b0C.Bacteria are most widely used as a microbial producer ofproteases, and the genus Bacillus is the most famous sourceamong them. Primarily, the reason is the strong ability tosecrete proteins, which allows to obtain >20 g of protein perliter of a medium . Furthermore, various Bacillus species produce neutral and alkalineproteases , andthis property is important for the industry. Proteases of Bacillus members have unique characteristics enabling their use inmany industrial sectors. Consequently, proteases from variousBacillus species are responsible for ~60 % of all the sales ofenzymes worldwide. Because of the wide ranges of pH andtemperature corresponding to good activity and stability, theseenzymes are used in the detergent industry .For this purpose, enzymes should be resistant to an alkalinemedium and retain their activity in the presence of inhibitors,including oxidants and surfactants. In addition, the proteasesisolated from the strains of Bacillus are suitable for the foodindustry for preparation of biologically active peptides andprocessing of various food products . Another feature of these proteases is stability inorganic solvents and the consequent suitability for organicsynthesis . Owing to the high commercialsignificance, a large number of patents deal with the strainsof Bacillus (see the Table).The widespread manufacture of proteases by means ofBacillus strains is due to the economic efficiency of thesestrains. Additionally, it is possible to utilize the byproductsof agricultural production as a substrate for these strains,e. g. molasses of sugarcane and corn starch for submergedfermentation or various types of branand solid residues for solid-state fermentation .Proteases are commercially important proteins responsiblefor the lion\u2019s share of protein manufacture. They have manyapplications, and each technological process has its specificfeatures and requirements for the enzymes used. Besides, theunrelenting interest in these proteins is due to the search forenzymes that are not covered by patents, albeit with properties that are not necessarily better than those of the existingenzymes. Accordingly, a huge number of research paperson this topic is published every year. The largest number ofgenes of alkaline serine proteases has been discovered in thegenomes of bacteria from the genus Bacillus. The secondplace in terms of isolation of proteases belongs to Actinomycetes. A substantial number of researchers also seek alkalineproteases of fungal origin . In the latestarticles, the emphasis is on the search for enzymes having a keratinase activity because of increased interest in the processing of keratin-containing residues, e.g., feathers.The source of one of the promising genes encoding a serineprotease is strain Bacillus licheniformis NMS-1 extractedfrom soil near a natural hot spring in Sri Lanka . This protein serves for the creation of detergents. Closely related strain B. licheniformis K7A expressingan alkaline protease was obtained in another study . Analysis of the expressed protein revealed thatit has the highest activity at pH 10 and 70 \u00b0C. The enzymaticactivity is higher than that of commercial preparations of Alcalase and Thermolysin. Another serine protease was foundin the genome of the bacterium Bacillus amyloliquefaciensFSE-68 isolated from a starter culture for soy fermentationin South Korea. Its amino acid sequence was determined byliquid chromatography with electrospray ionization tandemmass spectrometry (LC/ESI-MS/MS) and by whole-genomesequencing. In comparison with a homolog, i. e., well-studiedsubtilisin BPN from B. amyloliquefaciens, that enzymeshowed slightly higher stability in the absence of calciumions . The protein isolated from alkaliphilic strainBacillus luteus H11 manifested proteolytic activity at NaClconcentration up to 5 M, temperature 45 \u00b0C, and pH 10.5. In China, during a screening of thebacteria obtained from industrial fermentation of soy, investigators isolated strain B. subtilis MX-6, which overexpressesa nattokinase-like protein . Numerous recent studies on the search for new versionsof proteases of bacterial or fungal origin can be discussedad infinitum. Therefore, for a variety of reasons, advancesin the manufacture of proteolytic enzymes are still relevanttoday. This is especially true for developing countries, whichstrongly wish to increase the proportion of industrial products,including biotechnological ones, on their domestic markets.An especially large number of studies in this field has beenpublished by research groups from India. At present, suchstudies are virtually absent in Russia.Subtilisin is the industrial enzyme that has probably beenstudied the most by both statistical and directed mutagenesis. The applications of subtilisin have expanded constantlysince the start of its manufacture. To meet the needs of theindustry, subtilisin characteristics had to be improved. In theearly 1980s, the methods for directed engineering of proteinsstarted to develop rapidly. As a result of application of thesemethods to subtilisin, mutations of more than a half of its275 amino acid residues had been described before the year2000 in scientific literature. Patents contain even more suchaccomplishments, and, undoubtedly, an even greater numberof findings is buried in the freezers of biotech companies.Subtilisins represent a large class of microbial serine proteases, but the most mutagenized proteases are those fromB. amyloliquefaciens (BPNP), B. subtilis (subtilisin E), andBacillus lentus (Savinase).Protein engineering involves several effective methods thatinclude rational design and directed evolution. The formerusually implies the methods of site-directed mutagenesisfor replacing specific amino acid residues in a protein; thisapproach can help to obtain proteins with desired properties,such as higher thermal stability . Besides, protein engineering can help to elucidatesubstrate recognition and point to possible applications of anenzyme . On the other hand, directedevolution is based on the execution of sequential cycles ofmutagenesis and selection . Thus, researchersmay obtain enzymes with higher activity and stability undervarious conditions, including extreme pH and temperatures,nontraditional media, and modified specificity toward givensubstrates.Its stability has been urgently needed for its manufacture;in this regard, such studies have become widespread. An interesting feature of subtilisin is that its biosynthesis requiresparticipation of its N-terminal pro-domain . Folding of mature subtilisin without the pro-domain ispossible theoretically but will take thousands of years.An important characteristic of subtilisin is its tremendousdependence on calcium . The universal characteristic of subtilisins is the presence of one or more sites for calcium binding. High-resolutionX-ray structures of subtilisin BPNP and of several homologs have uncovered thedetails of a conserved calcium-binding site, which is calledsite \u0410. Calcium in this site is coordinately bound by fivecarbonyl atoms of oxygen and an asparagine acid residue.Four of the oxygen atoms are provided by the loop containing amino acid residues 75\u201383. The geometry of the ligandsis a pentagonal bipyramid, whose axis crosses the carbonylgroups of amino acid residues 75 and 79. On one side ofthe loop, bidentate carboxylate (D41) is located, and on theother, the N terminus of the protein and side chain Q2. Sevencoordinate distances vary from 2.3 to 2.6 A, the shortest ofwhich involves aspartyl carboxylateThe second ion-binding site (site B) is located 32 A awayfrom site A in a shallow cleft between two segments of thepolypeptide chain near the molecule\u2019s surface. The coordination geometry of this region bears a striking resemblance to adistorted pentagonal bipyramid. Three of the formal ligandsare derivatives of a protein and include an oxygen atom ofcarbonyl group E195 and two oxygen atoms from the carboxylate of the D197 side chain. Four water molecules completethe first coordination sphere.Given that the dependence on calcium is undesirable,some research has been conducted to obtain stable subtilisinsthat do not depend on the presence or absence of calcium insolution. One research group modified the amino acid sequence of subtilisin with a damagedcalcium-binding site for increasing this enzyme\u2019s stability.As a result, they obtained a mutant enzyme that is 15,000-foldmore stable than the original protein. To this end, 12 mutationswere introduced into the gene of this enzyme.The latest research on the modificationof alkaline serine proteasesIn spite of substantial progress in the development of customized properties of alkaline serine proteases, the work on theirmodification continues to this day. For instance, in one study, via directed evolution, the authors obtained seven mutants of a protease extracted from Bacilluspumilus BA06. They all possessed a higher proteolytic activity toward casein and a synthetic peptide substrate at 15 \u00b0\u0421.Except for T243S, thermal stability of these mutant enzymesdid not decrease relative to the wild-type enzyme. Combinations of mutations further increased the specific caseinolyticactivity. Double mutants P9S/K27Q and P9S/T162I showedapproximately a fivefold increase in the caseinolytic activity at 15 \u00b0C almost without a loss of thermal stability . In another study by the same group , directed mutagenesis was performed on the alkalineprotease of B. pumilus. The resultant double mutant (W106K/V149I and W106K/M124L) possessed 2.5-fold higher activity in comparison with the original enzyme at 15 \u00b0C, whereasits stability at 60 and 70 \u00b0C was 2.7-fold and 5-fold higher,respectively .During a comparison of halotolerant subtilisins with unstable ones, researchers discovered six amino acid positionswhere polar amino acid residues were replaced with nonpolarones. The researchers hypothesized that these substitutionsmay lead to higher thermal stability. To test this hypothesis,they carried out mutagenesis of the alcalase from strainB. subtilis No. 16 and subtilisin Carlsberg. As a result, therewas respectively 1.2-fold and 1.8-fold greater resistance ofthe enzymes to higher salt concentrations (125 g/L) . In another work , a serineprotease from Pseudomonas aeruginosa was modified at twopositions (A29G and V336I); as a consequence, they achieveda 5 \u00b0C increase in the temperature of observed residual activityand 1.4-fold enhancement of the catalytic activity . In yet another study , statisticalmutagenesis of an alkaline-protease gene discovered duringa metagenomic analysis increased the enzymatic activity by6.6-fold.The Bacillus bacteria have been the main microbial producersof serine proteases throughout the whole period of theirpractical use. Cultivation conditions and composition of themedia play an important role in the production of enzymesby microbes . To achieve high and commercially significant expression of proteases, it is crucial tofind the conditions for growth and induction . There is no universal medium suitable for all producerstrains. Each microorganism or strain has unique specificconditions for maximal production of a given enzyme. Letus review various parameters of cultivation in more detail.Carbon and nitrogen are the main components of a mediumand act as major stimulators of microbial growth and synthesis of enzymes. The most widespread source of carbonand often the cheapest (after starch) is glucose; however,during its consumption, the effect of catabolic repression ofmany biosynthetic processes may emerge in the cell. Thehighest production of the enzyme by bacterial strain AKS-4is observed at a glucose concentration of 1 %. Under theseconditions, the level of expression of the protease reaches59.10 U/mL . Higher production ofproteases in Bacillus pseudofirmus AL-89 was observed afterglucose addition, whereas for Nesterenkonia sp., the synthesisof protease AL-20 was found to be suppressed in the presenceof glucose . The highest production of alkaline protease (2450 U/mL) inB. licheniformis was achieved in a medium containing 60 g/L glucose. A further increase in its concentration led to an insignificant decrease in the production of the enzyme. Glucoseat a high concentration inhibited the synthesis of the enzymein Streptomyces ssp., and concentration 0.5 % was optimalfor the production of the enzyme, whereas 1 % was optimalfor growth . Production of a protease inP. aeruginosa MCMB-327 in a soy-tryptic medium decreasedby 95 and 60 % after the addition of glucose and fructose,respectively . In another work , investigators tried various sources of carbon, suchas glucose, lactose, galactose, and starch, for the productionof a protease by Bacillus aryabhattai K3. The highest production of the protease (622.64 U/mL) was observed with lactose(10 g/L) as a carbon source . Similarly,in yet another study , researchers foundthat for most of the analyzed isolates, secretion of the enzymeis optimal with lactose as a carbon source. B. licheniformisBBRC 100053 also manifested higher productivity in termsof a protease in culture media containing lactose as a carbonsource .Aside from simple sugars, investigators tried other carbonsources for the production of proteases. The addition of 5 %of starch resulted in the highest production of a protease byBacillus sp. 2\u20135 . Strain Bacillus clausii No. 58 grew well on various carbon sources basedon starch . Corn starch at 0.5 % yieldedthe highest productivity in terms of the protease, followed bywheat flour and wheat bran. Nonetheless, the addition of potatostarch lowered the titer of the protease, possibly because ofthe presence of protease inhibitors in potato . Wheat flour as a sugar source gave good results on theproduction of proteases by Bacillus sp. . Bacilluslaterosporus synthesizes proteases while utilizing variouscarbon sources; the best sources of carbon for the secretion ofthe protease are soluble starch, trisodium citrate, citric acid,and glycerol .Nitrogen sources also significantly affect the yield of adesired protein, and optimal sources vary among differentstrains. The highest level of protease production by strainBacillus cereus 146 was observed in the presence of a beefextract as a nitrogen source. The presence of a yeast extract,peptone, and tryptone improved the growth parameters ofcultures, but the amount of the desired protein was stillmodest . It was demonstrated in anotherstudy that tryptone increases the protease synthesis by strainBacillus sp. . Peptone was found tobe optimal for the production of a protease by B. licheniformis BBRC 100053 . The yeast extractcauses the biggest increase in the production of enzymes byBacillus sp. . In case of Bacillus sp.APP1, among all the tested sources of organic nitrogen, soyprotein meal noticeably raised the synthesis of an extracellularprotease . Some authors alsoreported that the addition of soy protein meal gave the bestresults in comparison with casein, gelatin, and peptone for theexpression of a protease by Bacillus circulans. When casein,peptone, the yeast extract, and a beef extract were tested asa nitrogen source for the synthesis of a protease by bacterial strain AKS-4, the highest expression was observed in thepresence of casein. Among the various sources of organicnitrogen, nonfat milk gave the highest yield of a proteasein the case of Bacillus caseinilyticus, followed by a maltextract, peptone, and the yeast extract. Ammonium chlorideas an inorganic source of nitrogen inhibits the synthesis of aproteinase The impact of pH on the expression level of a desired product is unique for each producer strain. For example, forthe expression of proteases in Bacillus sp. MIG and B. cereus SIU1, weakly acidicpH (6.3\u20136.5) was found to be optimal. In a weakly alkalinemedium (pH 8.0\u20138.5), researchers noted the highest levelsof expression for B. licheniformis IKBC-17 , B. subtilis IKBS 10 ,Bacillus macerans IKBM-11 , andB. amovivorus . In one study on eightisolates of Bacillus , it was revealed thatthe best conditions for the growth of bacteria involve pH 9.0,whereas the optimal pH value for the secretion of the enzymevaries between 8.0 and 10.0. pH 9 was found to be optimal forthe production of proteases in Bacillus sp. , Bacillus sp. APP1 , and B. proteolyticusCFR3001 . Higher starting pH was setup for the production of a protease by B. licheniformis TISTR1010 (pH 10.0) , for B. circulans(pH 10.5) , and for Bacillus sp. 2\u20135(pH 10.7) .Temperature is also a crucial parameter, and the optimaltemperature is unique for each strain. For P. aeruginosa PseA, B. licheniformis , Bacillus coagulans , B. cereus, P. aeruginosa MCMB-327 , P. chrysogenum IHH5 , and A. oryzae 637 , the optimaltemperature for the synthesis of proteases is 30 \u00b0\u0421. A loweroptimal temperature (25 \u00b0\u0421) characterizes B. circulans and Microbacterium sp. ,whereas in B. cinerea, the highest expression was documentedat 28 \u00b0\u0421 . At 37 \u00b0\u0421, the maximal level ofexpression was observed for the strains of Bacillus amovivorus, B. proteolyticus CFR3001 , Bacillus aquimaris VITP4 , and B. subtilis Rand ;at 40 \u00b0\u0421 for Bacillus sp. 2\u20135 ,Vibrio pantothenticus , and Streptomycesroseiscleroticus ; and at 50 \u00b0\u0421for Bacillus sp. APP1 and B. subtilis BS1.The synthesis of proteases is possible not only in the strainsof Bacillus but also in other bacteria and in yeast, e. g., in thestrains of Pichia pastoris. These strains naturally do not havea specific activity; for this reason, they require modification by genetic engineering. There are few such studies, and forthe most part, they are aimed at obtaining fungal proteases ormedically important proteases.In one study, B. Liu et al. (2014) performed an analysis ofexpression of the keratinase gene in B. licheniformis BBE11-1in three heterologous expression systems: in Escherichiacoli, B. subtilis, and P. pastoris. The highest (best) level ofexpression was seen in B. subtilis (3010 U/mL); this level wasthreefold higher than that in P. pastoris. It should be notedthat the cultivation of B. subtilis does not involve methanol, and cultivation duration is twofold shorter. In anotherstudy , there is a description ofcomparative cloning of the keratinase from B. licheniformisMKU3 in B. megaterium and P. pastoris. As a result, thoseauthors obtained comparable activities of the final culturewith the concentration of the desired protein at ~0.35 g/L.The protein from P. pastoris was subject to glycosylation.It should be mentioned that cultivation in a bioreactor wasnot described in that work. Similar results were publishedabout the expression of the keratinase from B. licheniformisPWD-1 .In one work , researchers investigated theexpression of the keratinase from P. aeruginosa in P. pastoris.The expression level was approximately 0.5 g of the proteinper liter. In this case, the protein did not undergo glycosylation. In another work , protein subtilisinQK (from B. subtilis QK02), which is highly similar to nattokinase, was cloned in P. pastoris GS115. Their objectivewas to obtain a protein with thrombolytic effects. As a result,they achieved a high concentration of total protein in the finalsupernatant (7.6 g/L). In this work, pH was maintained at 5.0,whereas in other studies and \u2013 the absence of pH control caused a pH increase, resulting in inhibition of microbial growth and a drop in keratinaseconcentration in solution. A similar picture was observed in astudy by H.H. Lin et al. (2009).Cloning of the alkaline protease from thermophilic bacterium B. stearothermophilus F1 was also conducted in P. pastoris GS115 . The resultant activity was4.13 U/mL; judging by the obtained molecular weight, theprotein was not glycosylated. In one study ,the gene of the alkaline protease from fungus Aspergillus sojaewas expressed in P. pastoris, and the final activity reached400 U/mL.The level of expression of a desired protein is strongly affected by codon usage too. In one work , asa result of optimization of codon usage in a gene, the levelof expression of the desired protein was raised relative to theoriginal gene. That study, however, does not present the data onthe cultivation under controlled conditions of a bioreactor. Anincreased copy number of the expression cassette also allowsfor improving the yield of a desired protein, as exemplifiedby a serine protease from the fungus Trichoderma koningii.In conclusion of this section, it is worth noting that thehighest accumulation of alkaline serine proteases is greaterin the P. pastoris expression system than in the E. coli expression system, but lower than that in standard B. subtilis strains.At the same time, the industrial strains of Bacillus spp. out perform both P. pastoris expression systems and B. subtilisby more than an order of magnitude. A 2005 patent describes strain B. licheniformis T1, which ensures theexpression level of a protein at 16 g/L, whereas the highestconcentration of keratinase produced in P. pastoris is approximately 0.1\u20130.2 g of the desired protein per liter.Alkaline serine proteases of the subtilisin family are widelyapplied in various industrial sectors. Proteases isolated fromBacillus bacteria constitute approximately 60 % of all enzymesales across the globe.Currently, native enzymes, i. e., those found in nature, arehardly used and have been ousted by the proteins modifiedvia genetic engineering and thus possessing better properties,e. g., thermal stability, general resistance to detergents andspecific resistance to various oxidants, high activity in various temperature ranges, independence from metal ions, andstability in the absence of calcium.At present, diverse strains of Bacillus serve as microbialproducers of alkaline serine proteases. Most of them originallyhad the desired activity, which has been enhanced by mutagenesis or genetic engineering. Among the producer strains,the species having the GRAS status dominate, that is, those that are even considered safeto eat: mostly B. subtilis and B. licheniformis. The strains thatoriginally did not possess a protease activity still cannot bebrought to the level of the native producers, even by meansof genetic engineering technologies.In literature, there are reports of the efforts to constructmicrobial producers of alkaline serine proteases on the basisof a methylotrophic strain of P. pastoris. In comparison withthe expression of the same genes in the genetically engineeredstrains of B. subtilis, the results have turned out to be noticeably worse. From the above observations, it can be concludedthat for constructing the strains effectively producing desiredalkaline proteases, it is necessary to employ Bacillus-basedexpression systems. 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David Mech, Dean Beyer, Erin Largent, Susan Dicks, John Oakleaf, the Mexican Wolf Project, Lindsey Dreese, Brent Patterson, Emily Almberg, Montana Fish Wildlife and Parks, Shari Willmott, and the countless unlisted biologists that collected these samples and data through the decades. Financial support includes: E.E.B. and P.J.H. endowment from Verne Willaman; E.E.B. and P.C.C. U.S. Geological Survey (Grant G17AC00427); D.W.S., D.R.S., and D.R.M. NSF LTREB grant DEB\u20131245373 and many donors to Yellowstone Forever, especially Annie and Bob Graham and Valerie Gates; M.H. Parks Canada and NSF LTREB award 1556248; G.R. Pittman-Robertson Federal Aid in Wildlife Restoration Program and the State of Alaska general funds; K.B. Federal Aid in Support of Wildlife Restoration and Alaska Dept. of Fish and Game; M.A. and H.S. British Columbia Ministry of Forests, Lands, Natural Resource Operations and Rural Development, Habitat Conservation Trust Foundation, Forest Enhancement Society of British Columbia; D.R.M and\u00a0M.A. Polar Continental Shelf Project and National Geographic Society; M.L.J.G. the Office of the Director, National Institutes of Health under award number NIH T32OD010993; T.W. Ontario Ministry of Natural Resources and Forestry; B.L.B. National Park Service; A.K. GNWT Environmental Stewardship Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. Government.\u201dThe original Article and accompanying Supplementary Information file have been corrected."} +{"text": "DOI: 10.1371/journal.pgen.0010065PLoS Genetics, volume 1, issue 5:In The list of contributing authors does not include Daniel H. Haft, whose name should have appeared between James F. Kolonay and William C. Nelson. He participated in analysis of the data."} +{"text": "PLoS Biology, volume 4, issue 12: doi:10.1371/journal.pbio.0040382In Because of an editorial error, the author contributions were printed incorrectly. The correct author contributions are printed below.Author contributions. IB and KS conceived and designed the experiments. IB and FvSP performed the experiments. IB and KS analyzed the data. IB and KS wrote the paper."} +{"text": "Eighteen patients with liver metastasis or locoregional recurrence of colon carcinoma received locoregional treatment by continuous 5-day infusions of 5-FU. 5-FU blood levels were measured by HPLC every day of the cycle at 8 am and 5 pm for a total of 87 cycles. Twelve patients were given the drug by an intra-arterial hepatic (i.a.h.) route, 3 by the portal vein (i.p.v.) and 3 by an intra-arterial pelvic (i.a.p.) route. These three routes were compared in respect of their relative pre-systemic drug uptake and the effect of dose escalation. Both the i.a.h. and i.p.v. routes, but not the i.a.p. route, resulted in a significant reduction in AUC 0-105 h compared to the i.v. route at the same dose range. Increasing the dose led to a modification in circulating 5-FU levels proportional to the dose for the i.v. and i.a.p. routes. By contrast, for the i.a.h. and i.p.v. routes, systemic drug delivery was significantly elevated, out of proportion with the dose, indicating a saturable process. For the i.a.h. route, increasing the 5-FU dose from 780 to 1000 mg m-2 day-1 caused a drop in hepatic extraction from 0.93 (0.90-0.95) to 0.44 (0.21-0.66). Liver saturation mechanisms were also evidenced by a mean increase of 2.6 times for the circulating drug level during the second part of the cycle as compared to the first part (P less than 0.001). The evolution of 5-FU AUC 0-105 h as a function of the dose was exponential . Local extraction consecutive to i.a.p. was non-existent, implying that this route of drug administration has no potential advantage over classical i.v. infusion."} +{"text": "Comparative genomics has provided valuable insights into the nature of gene sequence variation and chromosomal organization of closely related bacterial species. However, questions about the biological significance of gene order conservation, or synteny, remain open. Moreover, few comprehensive studies have been reported for rhizobial genomes.Sinorhizobium meliloti, Agrobacterium tumefaciens, Mesorhizobium loti and Brucella melitensis). We made a comprehensive gene classification to define chromosomal orthologs, genes with homologs in other replicons such as plasmids, and those which were species-specific. About two thousand genes were predicted to be orthologs in each chromosome and about 80% of these were syntenic. A striking gene colinearity was found in pairs of organisms and a large fraction of the microsyntenic regions and operons were similar. Syntenic products showed higher identity levels than non-syntenic ones, suggesting a resistance to sequence variation due to functional constraints; also, an unusually high fraction of syntenic products contained membranal segments. Syntenic genes encode a high proportion of essential cell functions, presented a high level of functional relationships and a very low horizontal gene transfer rate. The sequence variability of the proteins can be considered the species signature in response to specific niche adaptation. Comparatively, an analysis with genomes of Enterobacteriales showed a different gene organization but gave similar results in the synteny conservation, essential role of syntenic genes and higher functional linkage among the genes of the microsyntenic regions.We analyzed the genomic sequences of four fast growing Rhizobiales (Syntenic bacterial genes represent a commonly evolved group. They not only reveal the core chromosomal segments present in the last common ancestor and determine the metabolic characteristics shared by these microorganisms, but also show resistance to sequence variation and rearrangement, possibly due to their essential character. In Rhizobiales and Enterobacteriales, syntenic genes encode a high proportion of essential cell functions and presented a high level of functional relationships. A huge amount of information has been obtained from sequencing projects. More than two hundred complete microbial genomes are available to date in public databases and sequencing of a similar number is in progress . Many quChanges in gene sequence and chromosomal rearrangements constitute the main sources of genomic variability. Nonsynonymous substitutions in the first or second nucleotides of the codon change the encoded residue and are thus a driving force of natural selection. Genomic studies in bacteria regarding synonymous and nonsynonymous substitution rates have been published elsewhere ,3. ChromThe operon represents the first level of the gene organization. Neighboring genes, especially those in co-directional and in divergent orientation, represent a second organization level because they show a certain functional association revealed by genomic context analysis . RegardiBuchnera and Corynebacterium have low levels of chromosomal rearrangements and lack recA and recBCD orthologs, respectively , A. tumefaciens C58 (Cereon) [GenBank: NC_003062 and NC_003063], M. loti MAFF303099 [GenBank: NC_002678] and B. melitensis 16 M [GenBank: NC_003317 and NC_003318] were obtained from the Genome division of the NCBI Entrez system , were used for synteny and functional analysis. The genome of B. suis 1330 was used for synteny and sequence identity analysis. Genomes of Bradyrhizobium japonicum USDA110 [accession number GenBank: NC_004463] and Rhodopseudomonas palustris CGA009, also belonging to the alpha proteobacteria, were not considered in the main analysis because of their more distant phylogenetic relationship with the fast-growing rhizobia. To obtain a comprehensive view of shared genes among Rhizobiales, we differentiated genes by orthology and their presence in the same or different replicons in the analyzed species. Chromosomal orthologs were assigned by the best bidirectional hit between pairs of organisms, using the Fasta34 program [Results) and for detection of chromosomal genes with plasmidic homologs. Parameters were: an identity of at least 50%, overlapping by at least in 150 nt and an expectance (E) score of <10-3. The base organism for comparisons was S. meliloti 1021. GenBank accession numbers of proteins used for alignments in the order ArgB, ArgC, ArgD, ArgF, ArgG and ArgH, were as follows. Rhizobiales. R. palustris: NP_945982.1, NP_947833.1, NP_950107.1, NP_950106.1, NP_945745.1, NP_950077.1; B. melitensis: NP_541250.1, NP_540088.1, NP_540538.1, NP_540537.1, NP_540787.1, NP_539004.1; M. loti: NP_105609.1, NP_108547.1, NP_106269.1, NP_106270.1, NP_105253.1, NP_104594.1; A. tumefaciens: NP_353412.1, NP_354256.1, NP_353456.1, NP_353457.1, NP_355604.1, NP_357013.1; S. meliloti: NP_384545.1, NP_385346.1, NP_384623.1, NP_384624.1, NP_387315.1, NP_386753.1. Enterobacteriales. Buchnera sp.: NP_239886.1, NP_239885.1, NP_240341.1, NP_240186.1, NP_239887.1, NP_239888.1; E. coli: NP_418394.1, NP_418393.1, NP_417818.1, NP_414807.1, NP_417640.1, NP_418395.1; E. carotovora: YP_048320.1, YP_048319.1, YP_052152.1, YP_048510.1, YP_048232.1, YP_048321.1S. typhimurium: NP_457937.1, NP_457938.1, NP_458434.1, NP_458882.1, NP_457671.1, NP_457936.1; S. flexneri: NP_838925.1, NP_838926.1, NP_839526.1, NP_839629.1, NP_838682.1, NP_838924.1. All data sets are available on request.Available genome sequences of the fast growing Rhizobiales, z system . GenomesM. loti and B. melitensis I chromosomes were graphed so as to increase the colinearity in these replicons. The M. loti chromosome was segmented into two halves at 3.5 Mb position and the fragment covering from 3.5 to 7.0 Mb was located in the first position and then both halves were aligned with microsyntenic regions of S. meliloti. In the case of Brucella chromosome I, the origin was inverted. Graphs were obtained using the GenVision program . For operon similarity calculation, a limit of three different genes in each operon was allowed. All data sets are available on request.To consider chromosomal orthologs as syntenic among pairs of organisms, at least two genes must remain contiguous in both chromosomes. Microsyntenic region formation and extension fulfilled the following criterion: a pair of predicted orthologs separated from at least one other by no more than three genes (from the rest of categories). The minimal region was formed by a stretch containing three syntenic genes. Operon prediction was performed as reported by Moreno-Hagelsieb and Collado-Vides . Rearranet al. [A. tumefaciens, this rate was calculated using sequences and annotation obtained from the U. of Washington Sequencing Project [Prediction of horizontally transferred genes in the Rhizobiales genomes was performed using the method described by Medrano-Soto et al. . Briefly Project . SpeciesS. meliloti-M. loti comparison was graphed in progressive order. Then, corresponding predicted orthologs of the other comparisons were located at their corresponding identity percentages. Correlation coefficient values were calculated by the Pearson method. Plasmidic homologs and species-specific genes were not graphed because they have no counterparts in the pairs of analyzed genomes.The identity of peptidic sequences of chromosomal predicted orthologs were used to graph the distribution curves. The asymmetry of distribution curves, or skewness, was calculated by the asymmetry coefficient of Pearson (g1) as described elsewhere . To corrTheoretical proteomes were obtained by calculating molecular weight and isoelectric point for each translated chromosomal predicted ortholog. Both parameters were estimated with the pI/MW prediction tool of the Laquip Proteomic Team page . To deteAgrobacterium tumefaciens C58 in the U. of Washington genome report [S. meliloti chromosome, classes were assigned into Operational , Informational , and Cellular processes superclasses. This grouping, except for Cellular processes, is similar to that of Rivera et al. [Chromosomal predicted orthologs were assigned to the functional classes used for e report . For thea et al. . For funa et al. and STRIa et al. were usea et al. . Assignma et al. , with peGG and AA performed the computer predictions. HP made the functional analysis, interpreted the data and wrote the paper. RD and MAV participated in the work design. AM-S made the HGT and CRI analysis. JM conceived and directed the project. All authors read and approved the final manuscript.S. meliloti, according to the gene classification of predicted orthologs and homologs. Panels: (a), S. meliloti-A. tumefaciens comparison. (b), S. meliloti-M. loti comparison. (c), S. meliloti-B. melitensis comparison. Red striped bars, syntenic genes with the organism in comparison. Blue striped bars, non-syntenic genes with the organism in comparison. White bars, homologs with other Rhizobiales chromosomes At-C and (c) Bm-I chromosomes; upper fraction: with (a) At-L and (c) Bm-II chromosomes. Blue striped bars, non-syntenic genes, lower fraction: with (a) At-C and (c) Bm-I chromosomes; upper fraction: with (a) At-L and (c) Bm-II chromosomes.Schematic representation of the Rhizobiales chromosomes in comparison with Click here for fileS. meliloti in comparison with M. loti chromosome. Red bars, syntenic genes. Surrounded with yellow boxes, microsyntenic regions. Microsyntenic regions are denoted by letters (and numbers) in progressive order. Blue bars, non-syntenic genes. Green bars, homologs in plasmids. Gray bars, species-specific genes. White bars, homologs with other Rhizobiales chromosomes. Direction of transcription is denoted by upper (plus) or lower (minus) positions in respect to central line. Predicted operons are denoted by red arrows. Scale in bp.Synteny histogram of Click here for fileS. meliloti in comparison with B. melitensis chromosomes. Red bars, syntenic genes. Surrounded with yellow boxes, microsyntenic regions with B. melitensis chromosome I (Bm-I). Surrounded with light green boxes, microsyntenic regions with B. melitensis chromosome II (Bm-II). Microsyntenic regions are denoted by letters (and numbers) in progressive order. Dark blue bars, non-syntenic genes with Bm-I. Light blue bars, nonsyntenic genes with Bm-II. Green bars, homologs in plasmids. Gray bars, species-specific genes. White bars, homologs with other Rhizobiales chromosomes. Direction of transcription is denoted by upper (plus) or lower (minus) positions in respect to central line. Predicted operons are denoted by red arrows. Scale in bp.Synteny histogram of Click here for fileS. meliloti-A. tumefaciens circular chromosomes comparison. (b), S. meliloti-M. loti comparison. (c), S. meliloti-B. melitensis chromosome I comparison. (d), S. meliloti-E. coli comparison. (e), B. suis-B. melitensis chromosomes I comparison. Red dots, syntenic genes. Blue dots, non-syntenic genes. Scales in bp.Synteny of Rhizobiales and Enterobacteriales. Panels: (a), Click here for fileE. coli in comparison with E. carotovora chromosome. Red bars, syntenic genes. Surrounded with yellow boxes, microsyntenic regions with E. carotovora chromosome Microsyntenic regions are denoted by letters (and numbers) in progressive order. Blue bars, non-syntenic genes. Gray bars, non-orthologous genes. Scale in bp.Synteny histogram of Click here for fileS. meliloti-M. loti comparison. (b), syntenic and non-syntenic products from the S. meliloti-B. melitensis (chromosomes I and II) comparison. Y-axis, relative proportions. Red bars, syntenic genes. Blue bars, non-syntenic genes. Y-axis, relative proportions.Sequence identity distribution of chromosomal translated orthologs. Panels: (a), syntenic and non-syntenic products from the Click here for fileR. palustris; green, differences in B. melitensis; red, differences in M. loti; gray, differences in A. tumefaciens; violet, S. meliloti. (b), ArgC in Rhizobiales and Enterobacteriales. Identical residues for aech position are marked with yellow. Least abundant residues for a given position are denoted with an specific color for each of the species: Rhizobiales, same code of panel (a). Enterobacteriales: brown, Buchnera; pink, E. carotovora; blue, S. typhimurium. E. coli and S. flexneri, none. (c), data of the identity (*) and similarity (:*) in residues and in percentage (bold) of the alignments of the proteins in Rhizobiales and Enterobacteriales.Sequence alignments and data from the alignments of proteins from the arginine biosynthetic pathway in Rhizobiales and Enterobacteriales. Panels: (a), ArgC in Rhizobiales. Identical residues for aech position are marked with yellow. Least abundant residues for a given position are denoted with an specific color for each of the species: dark blue, differences in Click here for fileS. meliloti-M. loti comparison. (b), S. meliloti-B. melitensis (chromosomes I and II) comparison. Dots represent translated products. Scales in pH units.Theoretical isoelectric points (pI) of syntenic products. Panels: (a), Click here for fileS. meliloti, A. tumefaciens (circular) and M. loti.Summary of proteins with differential pI's from comparisons with chromosomes of Click here for fileS. meliloti-A. tumefaciens (both chromosomes) comparison. (b), S. meliloti-M. loti comparison. (c), S. meliloti-B. melitensis (both chromosomes) comparison. Dots represent translated products. Scales in pH units.Theoretical isoelectric points (pI) of nonsyntenic products. Panels: (a), Click here for fileS. meliloti- A. tumefaciens (circular chromosome) comparison.Functional categories of syntenic products of the membranal prediction of Click here for fileS. meliloti-A. tumefaciens comparison. Scheme belongs to the MetaCyc pathways for S. meliloti chromosome, used with permission. Highlighted with green, reactions covered with syntenic products.Metabolic pathways covered by syntenic products of the Click here for fileS. meliloti-M. loti comparison. Classes: 1) Translation, 2) Transcription, 3) Purine, pyrimidine, nucleoside and nucleotide metabolism, 4) Cellular processes, 5) Energy metabolism, 6) Cell envelope, 7) Fatty acid and phospholipid metabolism, 8) Biosynthesis of cofactors, prosthetic groups and carriers, 9) Transport and ATP binding proteins, 10) Amino acid metabolism, 11) DNA metabolism, 12) Regulatory functions, 13) Central intermediary metabolism. (b), S. meliloti-B. melitensis comparison. Classes: 1) Transcription, 2) Translation, 3) Cellular processes, 4) Biosynthesis of cofactors, prosthetic groups and carriers, 5) Cell envelope, 6) Energy metabolism, 7) Fatty acid and phospholipid metabolism, 8) Purine, pyrimidine, nucleoside and nucleotide metabolism, 9) Amino acid metabolism, 10) Transport and ATP binding proteins, 11) DNA metabolism, 12) Regulatory functions, 13) Central intermediary metabolism. (c), E. coli-E. carotovora comparison. Classes: 1) Biosynthesis of cofactors, prosthetic groups and carriers, 2) Purine, pyrimidine, nucleoside and nucleotide metabolism, 3) Translation, 4) Fatty acid and phospholipid metabolism, 5) Transcription, 6) Cellular processes, 7) DNA metabolism, 8) Energy metabolism, 9) Amino acid metabolism. 10) Cell envelope, 11) Regulatory functions, 12) Transport and ATP binding proteins, 13) Central intermediary metabolism. Note that order of classes is different to that in Fig. Coverage of functional classes with syntenic and non-syntenic genes. Panels: (a), Click here for fileS. meliloti (in comparison with A. tumefaciens) and (b) E. coli (in comparison with E. carotovora). Y-axis, connections per network. First syntenic networks, with 1060 (S. meliloti) and 810 (E. coli) connections, were omitted for clarity. Arranged in decrecent connectivity order. Gray bars, microsyntenic regions. Black bars, non-conserved regions. Successive networks, with connectivity values lower than 6, were omitted.Connectivity values from networks formed by microsyntenic and non-conserved regions in (a) Click here for file"} +{"text": "Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has been shown to be superior to bolus regimens in terms of response rates and toxicity. However, a continuous infusion is more expensive and prone to complications such as thromboembolism and infections. A way to circumvent these problems would be to administer 5-FU subcutaneously (s.c.). To assess feasibility and bioavailability of s.c. 5-FU, eight patients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The interpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local side effects were observed. To test the local tolerance of a more prolonged administration three patients received 930-1,000 mg m-2 5-FU by 24-h continuous s.c. infusion. The steady-state plasma levels were comparable to i.v. infusion. One patient developed a painless skin pigmentation at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose studied s.c. 5-FU has an almost complete bioavailability and is well tolerated. Further work will show, whether prolonged s.c. infusion can be used as a safe and economical alternative to i.v. infusion."} +{"text": "BeardJD, SteegeAL, JuJ, LuJ, LuckhauptSE, Schubauer\u2010BeriganMK. Mortality from amyotrophic lateral sclerosis and Parkinson's disease among different occupation groups\u2014United States, 1985\u20132011. MMWR Morb Mortal Wkly Rep2017;66(27):718\u2010722.28704346The puzzle of Parkinson's disease (PD) is particularly elusive, but the next part of the picture is appearing, and it is a curious one: a tale of men, mice, and flies. Recently, Beard and colleaguesAlthough this may appear (at first sight) far\u2010fetched, advantages in cognition in people at risk of PD are predicted from our studies of young PD\u2010mimic flies. These have faster, stronger visual responsesIncreased visual processing, and possibly faster neural signaling, as a result of deficits in retinal dopamine signaling may provide people at risk of PD with advantages in younger life, which impact before the later neurodegeneration. They may be more suited to jobs with higher socioeconomic status, both at interview and in the daily routine. This would explain the new observations.1 Ryan J.H. West, BSc, PhD2 Alex R. Wade, BA, PhD1 Christopher J.H. Elliott, MA, DPhil21Department of Psychology, The University of York, York, UK2Department of Biology, The University of York, York, UKMarc M. Himmelberg, BA, BPsych1) Research project: A. Conception, B. Organization, C. Execution; 2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3) Manuscript: A. Writing of the first draft, B. Review and Critique.M.H.M.: 3BR.J.H.W.: 3BA.R.W.: 3BC.J.H.E.: 3AMMH was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska\u2010Curie grant agreement No 641805. R.J.H.W. have nothing to disclose. A.R.W. and C.J.H.E. have (in the past 12 months) grants and nonfinancial support from Lundbeck A/S outside the submitted work. A.R.W. has support from Biotechnology and Biological Sciences Research Council (BBSRC)."} +{"text": "Rhodiola crenulata, a well-known medicinal Tibetan herb, is mainly grown in high-altitude regions of the Tibet, Yunnan, and Sichuan provinces in China. In the past few years, increasing numbers of studies have been published on the potential pharmacological activities of R. crenulata, strengthening our understanding into its putitive active ingredient composition, pharmacological activity, and mechanism of action. These findings also provide strong evidence supporting the important medicinal and economical value of R. crenulata. Consequently, some Rhodiola species are becoming endangered because of overexploitation and environmental destruction. However, little is known about the genetic and genomic information of any Rhodiola species. Here we report the first draft assembly ofthe R. crenulata genome, which was 344.5 Mb (25.7 Mb Ns), accounting for 82% of the estimated genome size, with a scaffold N50 length of 144.7 kb and a contig N50 length of 25.4 kb. The R. crenulata genome is not only highly heterozygous but also highly repetitive, with ratios of 1.12% and 66.15%, respectively, based on the k-mer analysis. Furthermore, 226.6 Mb of transposable elements were detected, of which 77.03% were long terminal repeats. In total, 31\u00a0517 protein-coding genes were identified, capturing 86.72% of expected plant genes in BUSCO. Additionally, 79.73% of protein-coding genes were functionally annotated. R. crenulata is an important medicinal plant and also a potentially interesting model species for studying the adaptability of Rhodiola species to extreme environments. The genomic sequences of R. crenulata will be useful for understanding the evolutionary mechanism of the stress resistance gene and the biosynthesis pathways of the different medicinal ingredients, for example, salidroside in R. crenulata. Rhodiola, in the family Crassulaceae, is a perennial herbaceous flowering plant and is mainly grown in the cool climate of subarctic areas, such as North America, Northern and Central Europe, and mountainous regions of southwest and northwest China. In general, Rhodiola species have similar morphology, causing difficulty and confusion in their taxonomic identification and classification [Rhodiola species have been used as traditional medicines for a long time, some being widely used for therapies of cardiovascular disease, hypobaric hypoxia, microbial infection, tumour and muscular weakness, the precise pharmacological mechanisms of actions are still unclear [Rhodiola species, R. crenulata is the most popular and in demand, but the supply of R. crenulata is limited due to its stringent growing requirement. The high selling price of R. crenulata causes serious problems of R. crenulata adulteration in the market. In order to improve the understanding of Rhodiola species, we have sequenced the whole genome of R. crenulata, and have subsequently completed the genomic assembly and annotation.Genus fication . Althoug unclear \u20136. In Chprotocol 1 (R. crenulata (NCBI taxonomy ID: 242839)Fig. . To redu839)Fig. .R. crenulata, which was collected from the Jade Dragon Snow Mountain, located in the northwest of Yunnan province, China, according to the protocol 2 (https://github.com/BGI-flexlab/SOAPnuke), we finally produced 13.23 Gb of high-quality clean data and predict the protein-coding genes inthe R. crenulata genome according to protocol 3 [Briefly, in terms of the repeat detection, first, RepeatScout , and Rep_012954) was util_012954) , 18 and _012954) . Overallde novo gene prediction, Augustus [Crassulaceae, we downloaded the protein sequences of model organism Arabidopsis thaliana and the relatively closely related species Fragaria vesca (https://www.ncbi.nlm.nih.gov/genome/3314?genome_assembly_id=34435), Prunus mume (https://www.ncbi.nlm.nih.gov/genome/13911?genome_assembly_id=44389), and Prunus persica (https://www.ncbi.nlm.nih.gov/genome/388?gen-ome_assembly_id=28754) in rosids, and then aligned these against the repeat-masked genome using BLAT [R. crenulata tissues were mapped to the consensus gene set by TopHat [Before gene prediction, TEs observed above were masked to reduce the interference. Regarding the _008417) , 20 and _008417) were coning BLAT . GeneWising BLAT , whose aing BLAT to integ_013035) , and the_013035) were exe_013035) , TrEMBL _013035) , and KEG_013035) databaseTo evaluate the completeness of the gene set and assembly, BUSCO was perfR. crenulata genome that we have sequenced, assembled, and annotated here was the first published genome in the genus Rhodiola and family Crassulaceae. The R. crenulata genome should serve as an important resource for comparative genomic studies, for further investigations of the adaptability of Rhodiola species in an extreme environment, and for the elucidation of the biosynthesis pathways of pharmacologically active metabolites in Rhodiola species.In summary, the Additional File 1: Supplementary Tables and Figures.docxAdditional File 2: Protocols.io.xlsbp: base pair; CDS: coding sequence; Gb: giga base; kb: kilo base; Mb: mega base; SRA: Sequence Read Archive; TE: transposable elements; WGS: whole genome shotgun sequencing.This work was supported by the National High Technology Research and Development Program of China (NO.2014AA10A602-4) and Basic Research Program Support by the Shenzhen Municipal Government (No. JCYJ20150831201123287) and Key Research & Development Program of Jiangsu Province (BE2016002-3).GigaScience database (GigaDB) [protocols.io [The DNA sequencing data have been deposited into the NCBI Sequence Read Archive (SRA) under the ID SRA538315. The RNA sequencing data are under ID SRA539059. Supporting data are also available from the (GigaDB) . DNA/RNAocols.io .The authors declare that they have no competing interests.S.M.Y.L., X.L., X.S., and X.X. designed the project. Y.F., L.L., S.H., R.G., G.F., H.W., W.C., and H.Z. analyzed the data. Y.F., S.M.Y.L., X.L., G.F., and C.S. wrote the manuscript. G.L., J.W., L.M., J.Y., X.N., and Z.Y. prepared the samples and conducted the experiments.GIGA-D-16-00153_Original_Submission.pdfClick here for additional data file.GIGA-D-16-00153_Revision_1.pdfClick here for additional data file.Response_to_reviewer_comments_original_submission_.pdfClick here for additional data file.Response_to_reviewer_comments_Reviewer_1.pdfClick here for additional data file.Reviewer_2_Report_(revision_1).pdfClick here for additional data file.Reviewer_3_Report_.pdfClick here for additional data file.Reviewer_4_Report_(Revision_1).pdfClick here for additional data file.Review_1_Report_.pdfClick here for additional data file.Review_2_Report_.pdfClick here for additional data file.Additional File 1:Supplementary Tables and Figures.docxClick here for additional data file.Additional File 2:Protocols.io.xlsClick here for additional data file.Additional_file_3_In-house_Perl_Script.pdfClick here for additional data file."} +{"text": "Am J Trop Med Hyg 95:1031\u20131036 by Cabada and others (https://doi.org/10.4269/ajtmh.16-0237), there was an error in the author list. Clinton A. White Jr. should have been listed as A. Clinton White Jr. The journal regrets the error.In"} +{"text": "It may cause unsatisfactory esthetics, dentinal hypersensitivity, root cavities, dental abrasion and other alterations. GR have a multifactorial origin, and could affect a significant part of the population with good oral hygiene. The aim of this study was to evaluate the relationship between GR and local trauma due to deleterious habits and inadequate oral hygiene comparing different research studies and case reports. Oral hygiene factors, such as toothbrushing duration, brushing force, daily frequency and toothbrushing technique, were associated with GR as well as toothbrush characteristics (bristle stiffness) and frequency of replacement. Deleterious habits like thumb- or pacifier-sucking, tongue interposition during swallowing, self-inflicted gingival mutilation cause gingival injury and may also be an important factor related with GR. Therefore it may be concluded that local trauma is one of the main factors that might start and/or lead to GR progression.002isinha_fav@hotmail.com); KASUYA, A.V.B.; FABRE, H.S.C.; QUAGLIATTO, O.S.; FONSECA, R.B.FAVAR\u00c3O, I.N. . After color selection (VITA shade guide), the maxillary anterior teeth were reshaped with direct bonding technique and then adjusted according to the principles of esthetic harmony and masticatory function. The maxillary anterior teeth showed better esthetic in terms of shape, texture and color, with excellent final outcomes. During dental transformation, professionals must examine all tooth structures, bearing in mind the anatomic and esthetic knowledge, and looking for an ideal model that will assist them during the esthetic and functional dental reconstruction.003fernanda_ada@hotmail.com); MECA, L.B.; LINS, S.A.; GAETTI-JARDIM JR, E.AZEVEDO, F.A. ; GALLO, A.J.; SOARES, A.S.; VIEIRA, E.M.M.; GAETTIJARDIM, E.C.SALINEIRO, F.C.S. ; NOGUEIRA, L.M.; TRINDADE, P.A.K.; PEREIRA FILHO, V.A.; GABRIELLI, M.F.R.FLORIAN, F. and forwarded to the Urgency and Emergency Service of the Santa Casa de Miseric\u00f3rdia Hospital of Araraquara. This work describes the approach of the patient by the Oral and Maxillofacial Surgery and Traumatology Team of Araraquara Dental School and the sequence of the treatment accomplished, as well as the techniques used for the reduction and fixation of the complex facial fractures. The patient presented favorable evolution without postoperative functional changes after years of treatment, demonstrating the importance of knowledge of the sequence of treatment in this type complex facial fracture.006nandagf18@gmail.com); SILVA, G.R.; CABRAL, F.C.; NOVAIS, V.R.; MARTINS, L.R.M.; SOARES, C.J.FARIA, F.G. . The main reasons for replacing restorations are: secondary caries, deficiencies on marginal adaptation or occlusal and proximal contact, staining and color change, roughness, loss of anatomical shape and brightness, and postoperative sensitivity. It may be concluded that only the appearance of the restorations should not be used as indicative of the need for replacement. The recontouring and repair are alternatives to the replacement of restorations, as they present advantages such as increasing the longevity of the restoration with low cost and preservation of tooth structures.007nandamargon@hotmail.com); STRINI, P.J.S.A.; MACHADO, N.A.G.; FERNANDES-NETO, A.J.; SOUSA, G.C.; BERNADINO, R.MARGON, F.O. subjected to therapy with occlusal splints. Twenty patients with signs and symptoms of TMD who met the inclusion and exclusion criteria participated in the study. The patients were assessed by clinical examination during which it was observed the side of mastication, occlusal interference and joint pain before and after 30 days of therapy with stabilizing occlusal splint. An acetate interocclusal device with maxillary full-coverage was made for each participant. These devices were relined with colorless autopolymerized acrylic resin and adjusted in centric relation with the disocclusion pattern by anterior guidance. The initial data were compared to results obtained after 30 days of use of the splint. It was observed that the installation of the device changed the side of mastication in 35% of patients; in 25% of these patients there was a shift from unilateral to bilateral mastication. Regarding the painful symptomatology, pain remission was observed in 50% of patients and the other 50% still had pain . It may be concluded that the therapy with occlusal splints is an important method in the remission of painful symptoms, capable of influencing the masticatory function and change the dynamic relations of occlusion.008flaviacassiacabral@hotmail.com); ROSCOE, M.G.; VALDIVIA, A.D.C.M.; SILVA, G.R.; NOVAIS, V.R.; SOARES, C.J.RODRIGUES, F.C.C. according to the factors: age, gender, relation of the etiology with other traumas, avulsed tooth, number of involved teeth, and development of tooth resorption. The results indicated that the most prevalent age range was between 6 and 12 years old (66.7%), being 66.7% of male individuals. In this age group, the predominant etiologies were fall (41.7%) and bicycle accident (41.7%). In older age groups, bicycle accident presented the highest frequency (44.4%), followed by fall (27.8%), motorcycle accident (11.1%) and fights (16.6%). The most commonly involved teeth were the upper central incisors (77.8%), 88.9% of the cases involving only 1 tooth and 11.1% involving 2 teeth. Tooth resorption (33.3%) is associated with the delay between the moment of accident and the first-care treatment, as well as to patient withdrawal after the first-care treatment and the beginning of the endodontic therapy with calcium hydroxide. The prevalence of dental avulsion in male patients aged 6-12 years due to falls and bicycles accidents shows the possibility of reducing this event with use of preventive measures, such as the use of mouthguards. The education of the population in looking for immediate care and the knowledge of the professional in starting as soon as possible the endodontic therapy are decisive factors for treatment success.009favivinha_zcs@hotmail.com); HON\u00d3RIO, H.M.; MAGALH\u00c3ES, A.C.; MACHADO, M.A.A.M.; BUZALAF, M.A.R.; RIOS, D.ZAIDAN, F.C. regular cola drink and (RCDP) regular cola drink with dental biofilm accumulation, 2nd phase- (LC) light cola drink and (LCDP) light cola drink with dental biofilm accumulation, 3rd phase- (SS) 8% sucrose solution (as contained in the regular cola drink) and (AS) 0.024% aspartame solution (as contained in the light cola drink), both with dental biofilm accumulation. Thus, in RC and LC, the specimens were fixed at the intraoral appliance surface level. In RCDP, LCDP, SS and AS, they were fixed 1.0 mm into the appliance level and covered by plastic meshes. The samples were demineralized extraorally 3 times daily for 5 minutes in the respective solutions. Enamel alterations were measured using profilometry and surface microhardness change (%SMHC). The data were tested by ANOVA and Tukey's test (p<0.05). Regarding enamel loss, RC (3.03 \u03bcm) showed significantly greater wear than the other groups, which did not differ significantly from each other . Regarding surface softening, the highest demineralization was observed for RC (-79.75) and LC (-64.10), which differed significantly between them and also from all the other groups, which, in turn, did not differ from each other . The light cola drink was less erosive than the regular one and the presence of dental biofilm reduced the erosive effect of both types of cola drink. Financial support: FAPESP (Proc. 2006/03874-8).This 010francinyionta@hotmail.com); GOYA, S.; SALES-PERES, A.C.; MOURA, P.G.; SALES-PERES, A.; SALES-PERES, S.H.C.IONTA, F.Q. and fluorosis (Dean index) indexes. Descriptive statistics was used and it was presented by means of relative and absolute frequencies. In the 13-year-old adolescents, the DMFT was 1.75 , 49.44% were free of caries and 18.89% presented some fluorosis level. In the 14-year-old adolescents, the DMFT index was 2.36 , 35.46% were caries free and 15.51% present some fluorosis level. The results showed that dental caries has declined and that fluorosis did not represent a public health problem in the studied city. Additionally there is a need to implement strategies that may guide actions and procedures towards individuals of major caries risk.011luff@usp.br); SCAFFA, P.M.C.; SILVA, L.M. NAHSAN, F.P.S.; SAMPAIO, P.C.P.; FRANCISCONI, P.A.S.FRANCISCONI, L.F. ; RODRIGUES, M.T.V.; GALV\u00c3O, N.S.; PINTO, J.M.V.; ALEIXO, R.Q.; COSTA, M.R.S.N.CUNHA, F.J.P. . Even considering other treatment options, the present case confirms better prognosis after lesion enucleation followed by surgical removal of the affected sublingual gland for complete resolution of this condition, minimizing lesion recurrence.013gasalles@gmail.com); MARQUES, V.R.; OROSCO, F.A.; GARCIA, R.B.; BRAMANTE, C.M.BARB\u00c9RIO, G.S. ; ROBERTO, A.F.B.; MARTA, S.N.OLIVEIRA, G.C. , maternal hypotension with effect on fetal hemodynamics, trauma during pregnancy and hyperthermia on the pregnant woman. The nerves affected by the disease are the abducent and the facial, but anomalies in other pairs of cranial nerves are also often observed, particularly the glossopharyngeal and the hypoglossal. The main clinical feature of the syndrome is the \u201cmask-like facial expression\u201d, that is, the lack of facial expression in situations of sadness or joy. The most frequent limbic malformations are finger hypoplasia in several degrees, sometimes reaching adactilia, and the club foot . Furthermore there can be alterations in the tongue, microstomia, micrognathia, convergent strabismus, high and narrow palate, and hearing problems. The treatment for the carrier of Moebius Syndrome should be conducted by a multiprofessional team comprising the different physical, cognitive, social and emotional needs of the patient. In this sense, this study describes the case of a patient with Moebius Syndrome highlighting the clinical and dental aspects as well as the dental treatment performed.015gabigennaro@hotmail.com); CLAUDINO, M.; SILVEIRA, E.M.; ASSIS, G.F.; TAGA, R.; GARLET, G.P.GENNARO, G. remain unknown. The aim of this study was to compare the role of TNF-alpha and IL-10 in the control of coupled bone formation in experimental periodontitis induced by A. actinomycetemcomitans in IL-10 (IL-10KO), TNFp55 (TNFp55KO) knockout and control (WT) C57Bl/6 mice. It was evaluated expression of bone formation markers OCN , ALP and CBFA1 by RealTimePCR. When compared to WT mice, IL-10KO mice presented a significant decrease in CBFA-1, OCN, ALP levels, which occurred concomitantly with an increased bone resorption activity , resulting in a higher level of bone loss. Conversely, TNFp55KO strain presented a lower bone loss rate, possibly due by decreased expression of bone resorption markers and increased levels of CBFA-1, OCN and ALP. Then, the results demonstrate that IL-10 and TNF-\u03b2 presented opposite roles in the modulation of coupled bone formation in inflammatory environments, being stimulate by IL-10 and inhibited by TNF-\u03b2.016gabinatalicio@gmail.com); CUNHA, M.J.S.; OLIVEIRA, P.G.F.P.; FIAMENGUI FILHO, J.F.; ALMEIDA, A.L.P.F.NATALICIO, G.L. ; 95.87% of teeth presented mean attachment level = 3 mm. The sextant with cleft did not present higher means of probing depth, clinical attachment level, plaque index and gingival index. There was no statistically significant difference between gender and the other variables. There was gingival bleeding and presence of biofilm in 99.69 and 97.40% of the sample, respectively, in both maxillary and mandibular teeth. The frequency and severity of gingival recessions were increased with age, affecting mainly the premolars and molars. The frequency of recession in incisors and canines was 10 times higher compared to the general population. The type of cleft was not an important factor influencing the prevalence of periodontal disease. Gender did not influence any of the clinical parameters in this sample. Age seems to be an important factor influencing the prevalence and severity of periodontal disease, for all aspects investigated. Periodontal disease in individuals with clefts, in the present study, occurred in a similar manner as observed in other populations. The presence of a cleft does not seem to increase the prevalence of the disease.017gabiulian@usp.br); PINTO, R.C.N.C.; ISHIKIRIAMA, S.K.; ISHIKIRIAMA, B.L.C.OLIVEIRA, G.U. procedure was associated to a connective tissue pedicle graft rotated (CTPGR) from the palatal region to reconstruct the interdental papilla in adjacent Miller class IV recessions. In addition, restorative procedures were performed on both affected teeth (#6 and #7) to improve the esthetic appearance. A healthy 39-year-old woman presented with compromised esthetics between teeth #6 and #7. Clinical and radiographic examinations revealed two Miller class IV gingival recessions involving these teeth with recession depths of 3 mm and 4 mm, respectively. IN addition, a Nordland & Tarnow class III interdental tissue loss of 7 mm was observed. After 1-year follow-up, the results demonstrated physiological probing depth and clinical attachment level gain with no clinically evident signs of inflammation in the gingival margin. There was complete coverage of recession (tooth #6) with an increase in papillary volume, an improvement in the gingival zenith position, and considerable reduction of the black triangle. Within the limits of this case report, the combination of the coronally advanced flap surgery and a connective tissue pedicle graft, complemented by restorative procedures led to a satisfactory esthetic outcome and may be a viable approach for the treatment of Miller class III and IV recession-type defects.018gabitfer@hotmail.com); SILVA-NETO, J.P.; COR\u00d3, V.; ARA\u00daJO, C.A.; DAVI, L.R.; NEVES, F.D.FERREIRA, G.T. , Branemark System MK III (NO) and conventional external hexagon (EH). The theoretical freedom was determined by means of an analytical model developed in the MATLAB software program, from mathematical expressions. The experimental rotational freedom was determined cording to manufacturers' testing. The results were subjected to the Student's t-test (p<0.05). The averages of the experimental and theoretical results were, respectively: IT 3.30 +- 0.17o and 3,34 +- 0.18o, NO 2.58 +- 0.35 and 2,81 +- 0.39o, EH 3,31 +- 0.41 and 3,62 +- 0.48o. No statistically significant difference could be found between the experimental and theoretical results for each type of implant evaluated. The relative error between the averages of theoretical and experimental rotational freedom was lesser than 10% for all implants analyzed. Therefore, the analytical model used in the MATLAB software is valid to determine the theoretical rotational freedom angle of each sample, with no need of making the measurements of rotational freedom angles in the experimental device.019cris_gambarini@yahoo.com.br); VERONEZI, M.C.; LEGRAMANDI, D.B.; BONELLI, A.C.C.; GOMES, C.C.; CARBALLEDA, G.S.GAMBARINI, C.T.A.G. ; PROVENZANO, N.; MARQUEZ, I.M.; ROCHA, F.S.; FURTADO, L.M.; ZANETTA-BARBOSA, D.SANTOS, G.S. (George Soares Santos Temporomandibular dysfunction (TMD) is a generic term that refers to pathologies of the temporomandibular joint (TMJ). For the precise diagnosis of this disease, it is necessary a comprehensive anamnesis as well as physical and complementary exams. Therapeutic procedures, such as medication and interoclusal splints can also be of great importance in the differential diagnosis and treatment. . Each type of joint disorder needs a different approach that may range from medication to open surgery. Arthrocentesis is the washing of the upper compartment of the TMJ aiming at removing debris and inflammatory mediators. This low invasive procedure can be used either for diagnosis or as definitive treatment of several affections of the TMJs, such as: temporomandibular disk displacement with and without reduction, synovitis and arthrosis. The objectives of this work are to make a brief review of the literature about arthrocentesis and to describe a clinical case of an 18 year-old woman with complaint of open mouth reduction with 15 days of evolution. The patient reported having heard a click in the left TMJ joint during yawning and could not open her mouth since then. The initial maxillofacial clinical examination showed open mouth limitation (22 mm), absence of right lateral movements and mandibular deviation to the left in maximum opening. After the anamnesis, clinical exam and complementary exams, the hypothesis of anterior disk displacement without reduction was established. Interoclusal splint therapy was used with little success. TMJ arthrocentesis was then used and the patient improved maximum mouth opening to 44mm and recovery mandibular movements.021aps.gil@hotmail.com); CARVALHO, A.C.G.S.; QUEIROZ, T.P.; MAGRO-FILHO, O.GIL, A.P.S. ; SOUTO, B.H.M.; OLIVEIRA, G.J.P.L.; SOUZA, J.A.C.; FONTANARI, L.A.; SAMPAIO, J.E.C.ANOVAZZI, G. ; BARBIERI, A.A.; ALVES, M.G.O.; ALMEIDA, J.D.GRACIO, A.C.M.M. ; SOARES, C.J.; BRANCO, C.A.; QUAGLIATTO, P.S.; FONSECA, R.B.PASQUINELLI, G.B.A. ; PEREIRA, J.R.; GHIZONI, J.S. VALLE, A.L.; OLIVEIRA, J.A.; ZOGHEIBE, L.V.COSTA, G.C. and groups 4, 5 and 6 were restored with prefabricated post and composite resin core with different combinations of post length . A compressive loading was applied at a 45-degree angle to the long axis of the tooth until failure. The two-way analysis of variance (\u00e1=.05) showed a statistically significant difference between the types of post (P<.001), among the different post lengths (P<.001) and showed a highly significant interaction between type of post and post length (P<.001). However, when the mean fracture forces for the groups were compared , no significant differences could be detected among the three groups restored with prefabricated posts and composite resin. This study showed that an increased post length in teeth restored with prefabricated posts does not significantly increase the fracture resistance of endodontically treated teeth. On the other hand, endodontically treated teeth restored with custom cast posts and cores showed a significant increase in fracture resistance when the post length was increased.026gferreiras@hotmail.com); TANOMARU-FILHO, M.; GUERREIRO-TANOMARU, J.M.; SASSO-CERRI, E.; CERRI, P.S.SILVA, G.F. , Endo-C.P.M.-Sealer (CPM) and zinc oxide and eugenol cement (ZOE). After 7, 15, 30 and 60 days, the animals were killed and the specimens were prepared to be stained with hematoxylin and eosin, Masson's trichrome and subjected to TRAP (Tartrate Resistant Acid Phosphatase) reaction. The morphometric analysis was performed considering three parameters: periodontal ligament thickness (PL), number of inflammatory cells (IC) and number of TRAP-positive osteoclasts in the alveolar bone surface. The experimental groups showed, in all periods, significant increase (p=0.05) in the PL thickness in comparison to the control group; this thickness being more accentuated in the ZOE group. The periodontal space in the CPM group was thinner in all experimental periods in comparison to MTA and ZOE groups, except for the period of 60 days; in this period, statistically significant differences in the periodontal space were not detected between CPM and MTA groups. At 7 days, a large number of IC was verified in all groups, especially in ZOE; from 7 to 60 days, the number of IC decreased gradually. Quantitative analysis revealed a significant increase in the number of TRAP-positive osteoclasts in the ZOE group, in all studied periods, in comparison to the other groups. In CPM and MTA groups, the number of osteoclasts was not significantly different in the periods of 15, 30 and 60 days. Moreover, in the 60-day period, no significant differences were observed in the number of osteoclasts among CPM, MTA and control group. Therefore, the present results indicate that MTA-based materials seem to be more biocompatible than ZOE.027guilherme.spagnol@uol.com.br); FREITAS, R.R.; SANTOS, P.S.S.; NAPOLES, B.B.SPAGNOL, G. (Guilherme Spagnol 3) on the day of admission. There were painful lesions on her tongue, gums and lips, with a vesicular-bullous center of approximately 0.5 cm and erythematosus edges and she mentioned having dysphagia. During her hospital stay, the patient received antibiotic therapy with the following drugs: ceftazidim, vancomycin, oxacillin, crystalline penicillin G and metronidazole but the febrile peaks did not diminish. Scarification of the lesion was carried out and the Tzanck method showed the presence of cells with viral inclusion on the tenth day of hospitalization, which led to the diagnosis of recurrent herpetic stomatitis. The patient was treated with a daily intravenous dose of 450 mg of aciclovir and a 3 times a day topical aqueous 0.12% chlorhexidine to prevent secondary infection of the lesions. She had just one febrile peak 24 hours after starting treatment with acyclovir and the fever ended after 48 hours. Within 3 days, the patient started to feed normally, with general clinical recovery. It may be concluded that the diagnosis, treatment and prevention of infections in immunocompromised patients are of great importance because they may have atypical presentations, making them difficult to diagnose.Patients subjected to chemotherapy become immunosuppressed and are therefore susceptible to infection. Bacterial, fungal and viral infections, such as cytomegalovirus, herpes simplex, varicella-zoster and Epstein-Barr, are associated with high morbidity among such patients. The viruses have similar clinical manifestations in the oral mucosa. The aim of this case report is to show the importance of the diagnosis and treatment of oral herpetic infection in immunosuppressed patients. A 20-month-old female patient with neuroblastoma, who had been receiving chemotherapy treatment for six months, was hospitalized one day after a course of chemotherapy. She had febrile peaks (39 degrees) and leucopenia (leukocytes 0.200/mm028ghb_andrade@hotmail.com); BRAMANTE, C.M.; BERNARDES, R.A.; MORAES, I.G.; BERNARDINELI, N.; GARCIA, R.B.ANDRADE, G.H. : AH Plus (G1), MBP (G2), Acroseal (G3), Sealapex (4), MTA sealer(G5) and two controls . The sealing ability was measured by using the fluid filtration model. Four measurements, one every 2 minutes for 8 minutes were analyzed after 15, 30 and 60 days. The fluid filtration model showed that Sealapex, Acroseal and MTA sealer showed an increment in the leakage in the period from 15 to 60 days. AH Plus and MTA sealer showed a decrease in the leakage pattern after 30 days. There was no significant difference in the sealing ability among the sealers except for Acroseal in the 30-and 60-day periods and Sealapex in the 60-day period. AH plus and MBP sealers had the highest sealing ability.029i.marote@hotmail.com); NARESSI, S.C.M.; BARBIERI, A.A.; QUELUZ, D.P.; SCHMIDT, C.M.; PREZA, A.O.MAROTE, I.A.A. and the comparative analysis of injury and models of the dental arches of the parents led to the conclusion that the bite mark had been produced by the child's father in an attempt to save her, according to reports from witnesses.030isanunes74@yahoo.com.br); CLAUDINO, M.; RAIUMUNDO, F.M.; COLAVITE, P.; REPEKE, C.E.; GARLET, G.P.NUNES, I.S. and antinflammatory (IL-10) cytokines expression in C57Bl/6 (WT) and CCR5KO mice after A. actinomycetemcomitans oral inoculation, and to correlate it with periodontal disease severity. After 0, 7, 15, 30 and 60 days of infection, alveolar bone loss and levels of TNF-alpha, IL-1beta and IL-10 expression were evaluated. CCR5KO mice presented a significant reduction (p<0.001) of bone loss after 30 days of inoculation. It was also verified that CCR5KO mice showed a significant reduction in TNF-alpha and IL-1beta expression (p<0.001), while only a trend of increased IL-10 expression (p>0.05) was observed. RANKL levels were reduced (p<0.01) in CCR5KO mice, possibly due by reduced levels of TNF-alpha and IL-1beta; while OPG levels were discreetly increased (p>0.05). Our results suggest that CCR5+ cells present a proinflammatory role in experimental periodontitis, regulating TNF-alpha, IL-1beta and RANKL levels.031isabellefreire@ig.com.br); SALZEDAS, L.M.P.; OLIVEIRA, S.H.P.FREIRE, I.R. subjected to periodontal disease (PD), demonstrated an increase in bone resorption when compared to normoglycemic mice. Thus, the purpose of the present study was to evaluate the role of mast cells (MAST) in the production of cytokines and chemokines induced by PD in mice with DM. Mice were pretreated with a single dose of streptozotocin (STZ) for induction of DM. To evaluate the role of MAST in PD, the mice were depleted of MAST by pretreatment with compound 48/80 (48/80). Subsequently, PD was induced using a ligature around the homologous first molars. Neutrophils (NE) recruited into the gingival tissue were evaluated by the production of myeloperoxidase enzyme (MPO), and the levels of IFN-gama, IL-4, RANTES/CCL5, KC/CXCL1 and Lymphotactin/XCL1 produced in tissue were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). It was observed the MPO levels were higher in diabetic and normoglycemic mice 14 days after the induction of PD. It was observed a partial reduction of MPO levels in diabetic mice with PD treated with 48/80. The level of IFNgama, IL-4, RANTES/CCL5, KC/CXCL1 and Lymphotactin/XCL1 was observed in diabetic mice independently of induction of PD after 7 or 14 days. In conclusion, DM increased the neutrophil recruitment in the PD mice. The MAST depletion decreased the recruitment of NE and it induced the production of high levels of IFN-gama, IL-4, RANTES/CCL5, KC/CXCL1 and Lymphotactin/XCL1, independently of induction of PD. Taken together, our results suggest that MAST may have a dual role on the PD under diabetic conditions.jackelineamaral@gmail.com); DELBEM, A.C.B.; SASSAKI, K.T.; MARTINHON, C.C.R.AMARAL, J.G. ; 500 \u03bcg F/g dentifrice; 500 \u03bcg F/g with Ca dentifrice; positive control: 1100 \u03bcg F/g dentifrice (Crest\u00ae). Enamel alterations were evaluated by the percentage of surface microhardness change (%SMHC). Fluoride measurement was performed using an ion-specific electrode. The amount of calcium and phosphate was analyzed by testing the colorimetric spectrophotometer. The statistical analysis showed that the placebo had higher percentage of mineral loss than the 500 \u03bcg F/g dentifrice. The 500 \u03bcg F/g with Ca and 1100 \u03bcg F/g dentifrices showed similar minerals losses and lower the other groups . The 1100 \u03bcg F/g dentifrice had higher concentration of fluoride, calcium and phosphate on the biofilm compared to others experimentals dentifrices, while the placebo dentifrice observed the lowest concentration of these ions . Based on this study, the low concentration fluoride dentifrices supplemented with calcium and phosphate showed similar results to the standard, being able to reduce the demineralization of bovine enamel under high cariogenic challenge.The aim of this study was to evaluate the effectiveness of low concentration fluoride dentifrices supplemented with calcium and phosphate on the demineralization of enamel and the dental biofilm formed 033jaine.zanolla@usp.br); SAMPAIO-TEIXEIRA, A.C.M.; YAMASHITA, R.P.; FUKUSHIRO, A.P.; TRINDADE, I.E.K.ZANOLLA, J. is routinely used for the correction of velopharyngeal insufficiency (VPI) in patients with cleft palate, based on the mechanical obstruction caused by the flap, which links the soft palate to the posterior pharyngeal wall, while two lateral holes are left for nose breathing. On the other hand, orthognathic surgery with maxillary advancement in this population has the potential to impair velopharyngeal closure, and cause hypernasality as a consequence. The purpose of this report is to present a clinical case of a patient subjected to orthognatic surgery followed by PFS, whose effects on speech resonance were evaluated by means of nasometry, a technique that allows the estimation of nasality. The patient had a surgically repaired unilateral cleft lip and palate. He was subjected to orthognatic surgery with maxillary advancement at 16 years of age and to PFS 9 months later. Nasometry was performed at the pre-and postoperative periods of both procedures during the reading of a set of oral sentences (OS) and nasal sentences (NS). A questionnaire was applied to assess respiratory symptoms. Nasalance scores obtained before orthognatic surgery corresponded to 37% (NS) and 17% (OS), indicating the presence of hyponasality without hypernasality The patient reported mouth breathing and left nasal obstruction. After orthognatic surgery (7 months), nasalance scores changed to 61% (NS) and 46% (OS), suggesting hyponasality elimination, with improvement of nasal breathing, and the development of iatrogenic hypernasality. After PFS (1 year and 3 months), scores corresponded to 49% (NS) and 15% (OS) demonstrating adequate oronasal resonance without respiratory complaints. The findings show that pharyngeal flap surgery is an effective option for the surgical treatment of VPI induced by orthognathic surgery with maxillary advancement.034janaina_miotto@hotmail.com); OLIANI, F.L.; BRANCO, C.A.; BUSO, A.M.; QUAGLIATTO, P.S.; FONSECA, R.B.MIOTTO, J.C. and esthetic disharmony . The lesions were exposed by periodontal surgery, increasing clinical crown and then provisionally restored with glass ionomer cement. The teeth were subjected to 2 sessions of bleaching with 35% carbamide peroxide and, after 21 days, closing the diastemata and dental transformations were performed with adhesive techniques and direct composite resin. After 24 hours, the restorations were polished with diamond pastes (medium and fine granulations) on rubber cups, and the final gloss was done with polishing brushes. The use of the above-mentioned techniques resulted in periodontal health and esthetic-functional improvement of the case. The Periodontics-Restorative Dentistry association by means of correct planning and rigorous esthetic perfection allows excellent outcomes, making it possible to maintain the health of dental and periodontal tissues.035zavitoski_foa@yahoo.com.br); FARIA, M.D.; CUNHA, R.F.SILVA, J.Z.; PAVAN, A.J.; FERREIRA, J.O.H.; VENTRINI, V.C.UCHIMURA, J.Y.T. . The profession of farmer made a percentage of 28.6%, followed by housekeepers with 16.3%. The TNM staging system, classification of malignant tumors, had 6.1% T0; 8.1% T1, 26.5% T2, 12.4% T3, 34.7% T4, 36.7% N0, 26.5% N1, 18.4% N2, 6.1% N3, 85.7% M0, and no case of M1. The pathological findings showed 93.9% of mucoepidermoid carcinoma, being 10.2% in the tonsils, 26.5% on palate, 26.5% in the tongue, 10.2% in the floor of the mouth, and 10,0% in the retromolar region. It was observed that 69.4% of patients smoked, and 32.7% of them for 30 to 50 years. It was observed that 28.6% smoked 4 to 6 packs/day and 8.2% of patients over 6 packs/day. It was observed that 38.8% of the studied population were alcoholics. This study allowed concluding that there is a urgent need of effective measures, capable of promoting, the reduction of the risk of becoming sick and the prioritization of actions to control the disease.037joaof11@usp.br); FERRAZ, B.F.R.; SANT'ANA, A.C.P.; PASSANEZI, E.; REZENDE, M.L.R.; GREGHI, S.L.A.BARROS, J.P.C. ; SILVA-NETO, J.P.; DANTAS, L.C.M.; CARNEIRO, T.A.P.N.; NEVES, F.D.SILVA, J.P.L. fractured at middle root third with avulsion of coronal portion after trauma to the anterior facial area. The treatment of choice was the extraction of the root remnant and implant installation in the same session (3i Self-Tap\u00ae - 18 x 3.75mm). GingiSCULPT - 3i\u00ae abutment, supplied in two pieces for single-session surgeries, was used to maintain the gingival contour; after abutment installation a provisory prosthesis was fabricated joined to the adjacent teeth with a fiberglass bar. After the osseointegration period, the AurAdapt abutment (Nobel Biocare\u00ae) was selected for further fabrication of the metallic framework, which received ceramic application for complete metal covering. At the same time, the natural tooth crown had its radicular portion worn out and the internal contents removed, leaving only enamel. Before the ceramic burning, the crown was positioned over the abutment, molding the internal portion on ceramic, still in the dough stage. After abutment personalization, the internal portion of the crown was relined with photoactivated composite resin to increase the adaptation to the abutment. Finally, the abutment was screwed to the implant and the crown was cemented over the abutment with dual resin luting cement. The use of this technique showed esthetic advantages with the preservation of the natural characteristics and disadvantages related to complex procedures and the future caries possibility. Over 10 years follow-up, the treatment was proven effective, preserving functional characteristics; however slight esthetic alterations were observed over time, though without compromising the patient's satisfaction.039jvreinato@yahoo.com.br); CARVALHO, F.L.N.; MARSICANO, J.A.; MATTOS, M.C.; PEREIRA, J.C.; SALES-PERES, S.H.C.REINATO, J.V.D. . The results suggest that the effect of both 10% and 30% propolis gels was similar to that of Oxa-gel in reducing dentin permeability. Further ex-vivo and in vivo studies must be conducted to clarify the real action of propolis in dentin permeability.The aim of this study was to evaluate the effect of two propolis gels on reducing the hydraulic conductance of dentin, 040jobagateli@hotmail.com); GABANA, M.L.; HIDALGO, M.M.BAGATELI, J.C.E. ; PELLIZZER, E.P.; F\u00c1LCON-ANTENUCCI, R.M.; CARVALHO, P.S.P.; VERRI, F.R.; ALMEIDA, D.A.F.SANTIAGO-JR, J.F. , with one implant with different diameters (3.75 and 5.00 mm), and a screwed crown, simulating a mandibular molar with abutments of different diameters (4.1 and 5.00 mm). Model A - Platform \u00d65.00 mm/abutment 4.1 mm (Platform Switching), Model B - Platform \u00d63.75 mm/abutment 4.1 mm and Model C - Platform \u00d65.00 mm/abutment 5.00 mm . The prostheses were standardized and made of NiCr alloy. In order to visualize the stress fringes, a circular polariscope was used, and axial loads of 100 N were applied by means of a Universal Test Machine (EMIC-DL 3000). The results were photographed and analyzed qualitatively in the image-editing program (Adobe Photoshop CS3). A greater intensity of stresses was observed in Model B (Platform \u00d63.75 mm/abutment 4.1 mm), with stresses concentrated around the body of the implant and at its apex. In models A (Platform \u00d65.00 mm/abutment 4.1 mm - Platform Switching) and C (Platform \u00d65.00 mm/abutment 5.00 mm), the fringe distribution patterns were similar, as the stress was concentrated at the level of the implant apex. In Model A, the stress concentration was more centralized along the axis and was less intense around the implant body. It was concluded that: 1) Model B presented the highest concentration of stress. 2) Model A and Model C presented similar stress distribution.042jorgianasangalli@hotmail.com); CIESIELSKI, F. I. N.; LINS, S.A.; GAETTI-JARDIM JR, E.SANGALLI, J. aged 18 to 55 years (mean age = 29.88 \u00b1 9.3 years) attending a detoxification program for drug dependents in the city of Santa F\u00e9 do Sul, and in a control group of non-dependent females, with similar age range and periodontal conditions. In the group of drug addicter, 19 had generalized gingivitis, 12 had chronic periodontitis, 13 were periodontally healthy, and 6 wore complete dentures. Samples of saliva and sub and supragengival biofilm were collected and the presence of microorganisms of Enterobacteriaceae and Pseudomonadaceae families, as well as 043juavansini@yahoo.com.br); SALES-PERES, A.; LAURIS, J.R.P.; CENEVIVA, R.; SALES-PERES, S.H.C.MARSICANO, J.A. , Dental Caries index (DMFT), the Dental Wear Index (TWI) were used to evaluate oral conditions. The oral exam was performed 16.9\u00b120.7 months after the bariatric surgery. The mean age of the group was 39.6\u00b19.6 and 75.00% of them were female. The patients had CPI of 3.05\u00b10.84, and 88.46% of them had at least one reference tooth with periodontal pocket depth between 4-6 mm. The DMFT was 16.11\u00b15.19; all patients presented history of dental caries and 71.20% presented the component \u201cdecay\u201d (D). All patients presented at least one tooth with dental wear, and 78.80% presented at least one tooth with dentin wear. The saliva flow was 0.64\u00b10.47 mL/min and 75.00% of the patients had hyposalivation. It may be concluded that the bariatric patients need attention in oral health and new research must be carried out for sedimentation of the scientific evidence in relation to the oral conditions of the patients undergoing bariatric surgery.044ksoldati@hotmail.com); REINO, D.M.; NOVAES JR, A.B.; PALIOTO, D.B.; MAIA, L.P.SOLDATI, K.R. has come as an alternative to the autogenous grafts and has been proven advantageous in increasing the keratinized gingival tissue width. One of the agents that can influence the treatment success of gingival retraction in mandibular anterior teeth is the vestibule depth, which hinders the hygiene and exerts a tensile action on the gingival margin. A case of gingival recession on the region of tooth #31 demonstrates the ADM technique application to increase the vestibule depth and the keratinized tissue width. A 20-year-old female patient came to the Periodontal Clinic of FORP \u2013 USP, complaining of the esthetic exposure due to a 7-mm gingival recession in the buccal face of tooth#31, in which root coverage was tried without success. After oral hygiene instructions, supra-gingival scaling and prophylaxis, a sliding flap was elevated. This procedure was chosen because the tooth had buccal tipping tending to the mesial, which resulted in an adequate width of gingival tissue in the distal area. However, flap necrosis occurred, probably due to the amplitude of the area to be covered, poor tooth position, and shallow vestibule. After 1 month of weekly biofilm control, a new surgical procedure was chosen to increase vestibule depth and keratinized tissue width. For this, ADM graft was done from teeth #33 to #43. Four months later, it was observed good healing, and increase of the keratinized tissue height and vestibule depth. In a later moment, a new surgical procedure for root coverage will be necessary. ADM may be useful to increase the keratinized tissue width and the vestibule depth, producing good esthetic and functional results.045karenaltr@gmail.com); ZAMPERINI, C.A.; PEREZ, L.E.C.; MACHADO, A.L.; VERGANI, C.E.; PAVARINA, A.C.ALTIERI, K.T. , the impact strength of a denture base acrylic resin (Lucitone-L), two direct reline resins (New Truliner-NT and Kooliner-K) and combinations of them. Twenty samples (60X6X4 mm) of each material were made and tested intact. Samples of L (60X6X2 mm) were also made and relined with L , with NT and with K . Before testing, half of the samples obtained were subjected to mechanical cycling . V-notches were machined at the midpoint of the length of all specimens. The analysis of the results (kJ/m2) by the Kruskal-Wallis test (\u00e1=0.01) showed that the mechanically cycled samples presented similar means compared to non-cycled samples , with higher values for the resin L, followed by resins K and NT. Similar results were observed for the relined samples. No statistically significant differences were found among the mechanically cycled and the non-cycled samples, with higher values for L/K, followed by L/L and NT. The mean value of the impact strength of L/L was similar to that of L, while L/K had higher value and L/NT had lower. In conclusion, mechanical cycling not have a significant effect on the impact strength of the resins evaluated. Under the two tested conditions, the material used in the relining influenced the impact strength, in the following decreasing order: L/K, L/L and L/N.046odonto_keila@hotmail.com); FERRARI, W.; BONOTTO, A.P.; SUKEKAVA, F.; ARAUJO, M.G.; ARRUDA, T.RODRIGUES, K. ; BRAGA, A.C.O.P.; MARQUES, I.S.V.; OLIVEIRA, P.G.F.P.; VALLE, A.C.BARBOSA, K.T. ; ARAUJO, A.C.; SOARES, C.T.; RUBIRA-BULLEN, I.R.F.; CERVANTES, O.; DAMANTE, J.H.TJIOE, K.C. biopsy was done in the cervical mass. The result of the sinus biopsy was actinomycosis without malignance. However, the nodular mass revealed to be metastatic squamous cell carcinoma in lymph node. Computed tomography (CT) and Positron Emission Tomography (PET) was prescribed to investigate the primary tumor that justify the lymph node metastasis. The primary tumor was not found. Surgical debridement of the sinus and neck dissection were performed. The histopathologic exams confirmed the first diagnostics. The tumor was a carcinoma of unknown primary site. Carcinoma of unknown primary site is defined as the histological diagnosis of metastasis without the detection of a primary tumor. Neck lymph nodes are the preferential sites. PET allows detection of primary tumor in about 25% of cases. In relation to the actinomycosis, correct diagnosis is difficult because the clinical and radiological findings closely resemble metastatic tumors and other infectious processes. The patient received radio/ chemotherapy and has been healthy for the past 15 months.049khamilafc@hotmail.com); OLTRAMARI-NAVARRO, P.V.P.; NAVARRO, R.L.; CONTI, A.C.C. F.; ALMEIDA, M.R.; ALMEIDA, R.R.CHIECO, K.H.F. ; REIS, M.V.P.; GOMES, J.B.; LIMA, J.H.F.; ORSI, I.A.SANTANA, L.S. , as well as to the correct determination, registration and maintenance of intermaxillary relations. By a literature review, it was verified that the etiologic factors that might be responsible for OVD alterations include dental anomalies, abrasion, erosion, parafunctional habits, loss of posterior support, restorative materials of different compositions and wear resistance, and unsatisfactory dentures. It was concluded that once the etiological factor is precisely identified, efforts must be focused on controlling the determinant factors as well as on disclosing the need for reestablishing the patient's OVD. Whenever the reestablishment of the OVD is required, the clinician should maintain it during all the phases of the rehabilitating treatment and further transfer the correct occlusal vertical dimension to the definitive denture.051larissamarinhoodonto@yahoo.com.br); CASAS-APAYCO, L.C.; MODENA, K.C.S.; FRANCO, E.B.; ATTA, M.T.AZEVEDO, L.M. coating used with a ultrasonic scaler provide an excellent cutting performance because they reach areas of the tooth that are inaccessible to high-speed handpieces. The use of this device allows the preparation of conservative and well finished cavity preparations. This case report shows benefits of the use of CVD diamond burs attached to ultrasonic dental scaler in the treatment of proximal caries. Sloping and different types of CVD diamond burs provide the access to proximal carious lesion with less pain and minimal noise, and no damages to the gingival tissues.052lari_mini@hotmail.com); CALABRIA, M.P.; WANG, L.; HANNAS, A.R.; PEREIRA, J.C.; MONDELLI, R.F.L.VASCONCELOS, L.R.S.M. ; OLTRAMARI-NAVARRO, P.V.P.;NAVARRO, R.L.; CONTI, A.C.C.F.; ALMEIDA, M.R.; ALMEIDA, R.R.SARAIVA FILHO, L. ; DEKON, S.F.C.; GABAN, G.; ZAVANELLI, A.C.; SILVA, C.R.PEREIRA, L.V. was planned, with ceramic system All-Ceram (Degussa). The cementation was done with resin self-etch cement. It may be concluded that the system used in this study has favorable esthetics when properly processed.055liamontagnolli@usp.br); BARBOSA, C.S.; KATO, M.T.; BUZALAF, M.A.R.MONTAGNOLLI, L.G. were randomly allocated to 5 groups (n=18/group), according to the treatments: Sensodyne Pro-Esmalte\u00ae , Sensodyne original\u00ae , Colgate Sensitive\u00ae , Crest\u00ae and water . The samples were subjected to 30 cycles, alternating re- and demineralization (5 days). Demineralization was performed with Coca-Cola\u00ae and remineralization with artificial saliva , at 37\u00b0C under agitation. Every 2 de-remineralization cycles, abrasion was conducted after demineralization, using an automatic toothbrush or water . The mean wear was significantly lesser for CSena (0.55\u00b10.03), SOrib (0.71\u00b10.02) and Crab (0.63\u00b10.13) when compared to SProc (2.38\u00b10.14) or Wtd (3.15\u00b10.17). These results suggest that the presence in dentifrices of fluoride or desensitizing substances alone or in combination can reduce the wear of enamel subjected to erosion associated with brushing abrasion, but this is not valid for all formulations.The aim of this study was to evaluate, 056livia-aguiarsantos@hotmail.com); MARTINS, L.M.; OLIVEIRA, P.C.G.; LORENZONI, F.C.; BONFANTE, G.; LOPES, L.D.S.SANTOS, L.A. . Thus, all-ceramic prosthesis became alternative materials to traditional metal-ceramic prostheses. However, even with improvements related to fracture resistance, all-ceramic crowns still present higher failure numbers compared to metal-ceramic prostheses. While metal-ceramic systems present biological problems as the main cause of failures, all-ceramic systems present mechanical problems (fracture of coverage or framework ceramics). The pattern of failure of all-ceramic systems depends on the ceramic material, its composition, shape and size of crystalline phase granules. Therefore, in terms of mechanical reliability, rates of metal-ceramic system survival are still the goal to be achieved by all-ceramic crowns. In the metal-ceramic systems, there is no difference between regions; on the other hand, the clinical reliability of all-ceramic systems on the anterior region is higher than on the posterior region. The aim of this study was to describe and discuss main failure modes present in the various ceramic systems by means of a case report.057liviacomar@usp.br); WIEGAND, A.; MAGALH\u00c3ES, A.C.; NAVARRO, R.S.; RIOS, D.; BUZALAF, M.A.R.COMAR, L.P. to prevent enamel and dentin erosion. Bovine enamel and dentin samples (n=10 each/group) were pretreated with CO2 laser irradiation (group I); TiF4 ; CO2 laser irradiation prior to (group III) or through (group IV) TiF4 application; AmF or CO2 laser irradiation prior (group VI) or through (group VII) AmF application. Controls remained untreated. The samples were then subjected to erosive demineralization and remineralisation cycling for 5 days. Enamel and dentin loss was measured profilometrically after pretreatment, 1st day (4 cycles) and 5th day (20 cycles) of pH cycling. The data were analyzed statistically by ANOVA and Scheffe's post-hoc tests (p<0.05). SEM analysis was performed in pretreated but not cycled samples (n=2/group). After 5th day, enamel loss was significantly decreased in group V and IV, while dentin loss was significantly reduced in group V only. All other groups were not significantly different from the controls. Lased surfaces (group I) appeared unchanged in the SEM images. However, microscopic images of enamel, but not of dentin, showed that the formation of fluoride precipitates was affected by CO2 laser irradiation. Thus, AmF decreased enamel and dentin erosion but its efficacy was not improved by CO2 laser irradiation. TiF4 showed only a limited capacity to prevent erosion, but CO2 laser irradiation enhanced its ability to reduce enamel erosion to a significant level.This 058lifinoti@msn.com); CHIARELLI, F.M.; BORGES FILHO, F.F.; ANOVAZZI, G.FINOTI, L.S. inserted in the palatal papilla will prevent natural diastema closure between maxillary central incisors after permanent lateral incisors and canines eruption. Pathological ULF, also known as persistent tectolabial frenum, is present in few adult patients, their usual complaint is about unsatisfactory esthetics because of the median diastema that may persist even after orthodontic closure when this frenum is not removed. Frenectomy is the complete excision of the frenum including its attachment to the underlying bone. One technique to remove it is the conventional approach using periodontal incisions with scalpel. The aim of this case report is to demonstrate with details a frenectomy of a pathological ULF where a different approach was done to reduce bleeding and surgery time. The patient presented a pathological ULF and a 7 mm diastema between upper central incisors, and was willing to receive orthodontic treatment in order to close this space. Surgical removal was then indicated prior to median diastema closure. After the healing period the ULF was normal and present in a more apical position, there was an increase in attached gingival height and vestibular depth.059lorraine_vs@hotmail.com); RAPOSO, L.H.A.; SOARES, P.V.; SOARES, C.J.SOUZA, L.V. ; GARCIA, L.F.R.; MARQUES, A.A.F.; PIRES-DE-SOUZA, F.P.C.; CONSANI, S.ROSELINO, L.M.R. , according to period of sacrifice . As part of the surgical procedure, four incisions were made on the dorsal region of each rat, where four dentin tubes filled with the tested materials were implanted in the subcutaneous tissue, as follows: GI - Epiphany/Resilon without primer; GII - Epiphany/Resilon associated with self-etch primer; GIII - Endofill/gutta-percha points (positive control) and GIV - empty tube (negative control). After 7, 21 and 42 days, animals were killed, obtaining 5 samples per group, at each analyzed time. From the morphologic and morphometric analyses, using a score system (0 - 3) (100x), results showed that Epiphany/Resilon system (GI and GII) induced a mild (1) inflammatory reaction after 42 days. However, in GI, in which the primer was not applied, extensive necrosis and a severe (3) to moderate (2) inflammatory reaction were observed, between 7 and 21 days. When compared to the control groups, it was observed that these groups presented tissue reaction ranging from mild (1 - 7 and 21 days) to absent (0 - 42 days). In conclusion, Epiphany/Resilon root-canal filling system presented satisfactory tissue reaction, being biocompatible when tested in subcutaneous tissues of rats.061lucas_homse@yahoo.com.br); CAVALIERE-PEREIRA, L.; PASTORI, C.M.HOMSE, L.C. ; DUARTE, N.T.; PRATES, L.F.; NAKAMUNE, A.C.M.S.; SALZEDAS, L.M.P.; DORNELLES, R.C.M.LAHR, L.P. were selected after analysis of estrous cycle, and ovariectomized (OVX). After 15 days, the animals received pellets containing corn oil or estrogen with 100 or 200 \u00ecg of 17\u00e2\u2013estrogen, during 60 days. After this period and under anesthesia , blood was collected from the jugular vein and the animals were sacrificed by anesthetic overdose for removal of the femurs. The blood was centrifuged and plasma stored in a freezer for subsequent biochemical determination of calcium and phosphorus. The femurs were tested on the three-point bending, axial compression was applied to the condyle and bone densities were analyzed using Digora digital system. The results showed no statistically significant difference in the analysis of the middle third of the three experimental groups. However, the optical density was lower in the condyle of the femur in the group of animals that received 200 \u00ecg of estrogen for 60 days. The plasma concentration of phosphorus in the group of OVX animals treated with 100 \u00ecg/estrogen was significantly lower and calcium was similar between groups. These results suggest there are important differences between the axial and appendicular skeleton in terms of the response to different doses of estrogen.063lucelmapieri@usp.br); HENRIQUES, J.F.C.; FREITAS, M.R.; JANSON, G.; PINZAN, A.; PUPULIM, D.C.PIERI, L.V. (Lucelma Vilela Pieri The Interlandi Head Gear appliance (IHG) with occipital anchorage or mean traction is indicated in Class II Division 1 treatment with maxillary and/or dentoalveolar protrusion, maxilla with normal transverse dimensions and mandible well positioned. The IHG headgear influences significantly bone and soft tissue profile providing a harmonious profile, mainly in growing patients with vertical pattern or increased LAFH. The upper right and left first molar tubes are placed on a cervical position. The external and internal arches are parallels to the occlusal plane with the external arch 2 cm longer than internal one. Variations in the angulations of elastic \u00bd inch over the occlusal plane with individual ideal forces from 350 to 600 g bring about effects and action mode according to the facial types and desired effects when inserted in the extremities of external arms and attached to occipital traction of Interlandi type. The upper molar crowns can move more than their roots with angulation below 15\u00b0 with extrusion in the horizontal and normal pattern. From 15\u00b0 to 20\u00b0 of angulation, the force pass through the molar's center of resistance (trifurcation area) causing a bodily movement of the upper molars to distal with extrusion restriction in the normal to vertical pattern. The roots and crowns move to distal practically in the same proportion. An angulation more than 20\u00b0, the roots start to move distally more than crowns with slight \u201cintrusion\u201d in severe vertical pattern and/or increased LAFH. More this angulation is increased more the roots move distally and the upper molar extrusion is restricted. A 9-year old girl with convex profile and severe horizontal trespass, without any space for the eruption of the permanent upper lateral incisors treated with an IHG appliance (20\u00b0 angulation and 350g each side) worn 24 hours/day for seven months will be presented. The upper and lower fixed appliances were placed to align and level the teeth. The IHG was efficient in moving upper molars distally with a body movement once the forces passed through the center of resistance bringing about sufficient space for eruption of the permanent teeth and a harmonic facial profile.064luciana_ayumi@hotmail.com); ASSIS, G.F.; CESTARI, T.M.; CEOLIN, D.S.; TAGA, R.KUROKAWA, L.A. and apoptosis (TUNEL method) in periods of 1, 3 and 6 months of induction of diabetes in rats. The figures were compared among groups by analysis of variance (ANOVA) at the level of 5%. Over the 6 months of experimental diabetes: a) the mass of the submandibular gland decreased according to the reduction of acini and granular ducts b) the absolute volume of acini decreased mainly because the volume of acinar cells and granular ducts on the basis of cell volume and number of cells c) the number of acinar cells and granular ducts that are produced and die has a low rate close to the physiological condition, the apoptosis being slightly larger than the proliferation, thus leading to reduction of the mass of submandibular gland. It may be concluded that diabetes induced by Alloxan over 6 months in rats caused a gradual decrease in submandibular gland as a function of the cell volume and the greater occurrence of death of cells of the secretory system, particularly the granular ducts.065lucianamfernandes@usp.br); RUBIRA-BULLEN, I.R.F.; CAPELOZZA, A.L.A.FERNANDES, L.M.P.S.R. evaluation of the region to be studied. The absence of superimposition of the structures in tomographic images and the obtaining of illustrative 3-D reconstructions are advantages of this new technology. The exam is easy and quick to perform and offers convenience to the patient. The purpose of this presentation is to introduce the main features, advantages and applications of i-CAT , illustrated with cases in which this technology has been applied.066ludmilabertato@yahoo.com.br); PIERI, L.V.; HENRIQUES, J.F.C.; JANSON, G.; FREITAS, M.R.; PINZAN, A.BERTATO, L.P.1 will be presented. This patient was treated with dental compensations, extraction of teeth #14 and #24, mesialization of tooth #48 and implantation of tooth #46. The orthodontic treatment in adults should have a multidisciplinary approach for success to be reached and maintained after the retention orthodontic phase.067luizneto@usp.br); LORENZONI, F.C.; COSTA, M.D.; MARTINS, L.M.; BONFANTE, G.OLIVEIRA-NETO, L.A. ; AYUB, B.; NASCIMENTO, B.M.; BELEZE, P.; ALCALDE, M.P.; SILVEIRA, E.M.V.GRACINDO, L.F. ; SILVEIRA-J\u00daNIOR, C.D.; NEVES, F.D.; FERREIRA, F.M.; SIMAMOTO-J\u00daNIOR, P.C.CAVALCANTE, L.A.L. , GT10 and GT20. Before welding, manual torque simulating routine laboratory procedure was applied to GTM. In GT10 and GT20, the abutment screws received 10 and 20 Ncm torque, respectively. After welding, the implant/framework interfaces were assessed by optical comparator microscope using two methods. First, the single screw test (SST) was used, in which the interfaces of the screwed and non-screwed abutments were assessed, considering only the abutments at the framework extremities. Second, the interfaces of all the abutments were evaluated when they were screwed. In the SST, intergroup analysis showed no significant difference among the three conditions of tightening force; that is, the different tightening force before welding did not guarantee smaller distortions. Intragroup analysis (Wilcoxon) showed that for all groups, the interfaces of the non-screwed abutments were statistically greater than the interfaces of the screwed abutments, evidencing distortions in all the frameworks. ANOVA was applied for the comparison of interfaces when all the abutments were screwed and showed no significant difference among the groups. Under the conditions of this study, pre-welding tightness on abutment screws did not influence the vertical fit of implant-supported metal frameworks.070luizneto@usp.br); LORENZONI, F.C.; COSTA, M.D.; MARTINS, L.M.; BONFANTE, G.OLIVEIRA-NETO, L.A. ; RIOS, D.; MOINO, A.L.; MAGALH\u00c3ES, A.C.; HON\u00d3RIO, H.M.; BUZALAF, M.A.R.CASSIANO, L.P.S. and immersed in the regular or light/sugar zero version of the following drinks: Coca-cola, Guaran\u00e1, Sprite and passion fruit juice . Half of the surface of the specimens was coated with nail varnish for reference. The samples were subjected 3 times daily to erosive challenges (30 mL beverage/sample) for 5 minutes at room temperature, under agitation. Between the erosive challenges, the samples were immersed in artificial saliva (30 mL/sample) for 5 h, at room temperature. In each day, after the pH-cycles the samples were stored in artificial saliva. At the 5th day, the dentin surface alterations were measured by profilometry (\u03bcm). The data were analyzed by ANOVA followed by Tukey's test (for cola drinks) and unpaired t test (for other beverages) (p<0.05). There were significant differences between the regular and light beverages, except for the regular and light passion fruit juices (regular: 2.43\u00b10.66 and light: 2.36\u00b10.61). Regular coke (2.53\u00b10.39) provoked a similar dentin wear compared to zero coke (2.46\u00b10.49), but both caused higher dentin loss compared to light version (1.88\u00b10.35). On the other hand regular Guaran\u00e1 (2.35\u00b10.51) provoked lower dentin loss compared to light one (2.88\u00b10.69). Regular sprite (2.49\u00b10.59) also provoked lower dentin erosion compared to light version (3.09\u00b10.72). Thus, this in vitro study showed that regular and light drinks might have different performances with regard to dentin erosion, with exception of the fruit juice.This 072maisacjordao_usp@hotmail.com); REBELATO, R.; MAGALH\u00c3ES, A.C.; HON\u00d3RIO, H.M.; BUZALAF, M.A.R.; RIOS, D.JORDAO, M.A. and immersed in the regular or light/sugar zero versions of the following drinks: Coca-cola, Guaran\u00e1 and Sprite. The samples were subjected 4 times per one day to erosive challenges (30 mL beverage/sample) for 2 minutes at room temperature. Between the erosive challenges, the samples were immersed in artificial saliva (30 mL/sample) for 2 hours. After each immersion , the enamel surface alterations were measured by superficial microhardness test (KHN). The data were analyzed by ANOVA followed by Tukey's test (for cola drink), unpaired t test (for guaran\u00e1) and Mann Whitney test (for sprite) (p<0.05). On all measurements, light cola provoked a similar enamel demineralization compared to zero cola, and both caused less demineralization compared to the regular version. The enamel microhardness change of regular and zero Guaran\u00e1 did not differ from each other, on all of the 4th immersions. However, zero sprite resulted in higher demineralization when compared to regular sprite, only in the 3rd and 4th erosive challenge. This in vitro study showed that the light and zero cola drinks promoted less enamel demineralization, but this was not observed for the zero versions of guaran\u00e1 and sprite. Financial support: FAPESP (Proc. 2006/07260-4).A previous 073manu_verdinelli@hotmail.com); SANTANA, L.S.; GOMES, J.B.; ORSI, I.A.; ONO, R.; GERV\u00c1SIO, A.M.REIS, M.V.P. ; SILVA-NETO, J.P.; SIMAMOTO-J\u00daNIOR, P.C.; ARA\u00daJO, C.A.; NEVES, F.D.; N\u00d3BILO, M.A.A.PRUDENTE, M.S. and G3 with three implants (n=3). The photoelastic models were built starting from six metal frameworks. Force of 1.33 kgf was applied in one distal extension of the prosthesis, evaluating the stress gradient in 16 points distributed along the implants. The shear bond stress was determined using the equation of the optical law of the tensions. From the analysis of the obtained values, normalized by G5, it was observed that G3 presented values of tension 12% greater than G5 in the cantilever area, while the other implants also presented higher values, but the difference was very small. Based on the obtained results it was observed greater values of shear bond stress in all implants from G3, when compared to their counterparts in G5, with greater concentration in those adjacent to the cantilever area. In spite of this, given to the practical and economical advantages of the protocol with three regular implants, further studies are needed before it can be established as a routine clinical protocol, benefitting a larger number of individuals. It is suggested, from the exposed, a similar work increasing the diameter of the implants.075garletgp@usp.br); CARDOSO, C.R.; ASSIS, G.F.; MARTINS JR, W.; TROMBONE, A.P.F.; GARLET, G.P.CLAUDINO, M. , but usually inconclusive or negative results have been found, possibly due an inappropriate case-control experimental design. Indeed, the inclusion of periodontally healthy subjects as a control population does not assure that this individuals are genetic susceptible to PD. The objective of study was to evaluate the potential of chronic gingivitis subjects, exposed to a chronic bacterial and inflammatory challenge but without evidences of bone loss, to be included as a genetically-resistant population in PD genetic association studies. Therefore, we investigated the frequency of different functional SNPs (single nucleotide polymorphisms) IL10-592, TNFA-308 and IL1B-3954 in healthy (H/n=190), chronic periodontitis (CP/n=178) and chronic gingivitis (CG/n=153) subjects. Using the traditional H vs CP approach, our results demonstrated a lack of association regarding TNFA-308 ((p=0.1882/OR=0.7265)), and weak to moderate association to IL10-592 and IL1B-3954 . However, when the alternative CG vs CP evaluation is analyzed, stronger statistical values were found to TNFA-308 , IL10-592 and IL1B-3954 , suggesting that a comparison between susceptible (CP) and resistant (CG) subjects is a more suitable approach to unravel the association of SNP with PD outcome. Indeed, based on PD natural history literature data, H group virtually include (approximately 70%) susceptible and (30%) resistant subjects, but the proper microbial control does not allow the distinction between these opposing phenotypes within H groups. Surprisingly, when H and CG groups were compared, no significant variations in the frequency of the SNPs investigated were found. Therefore, our results demonstrated that CG/CP analysis provide a more appropriate and powerful tool to investigate the genetic basis of PD susceptibility/resistance than the traditional H/CP approach; and also reinforce the hypothesis that CG patients may present a potentially genetically-resistant background regarding PD development.076marcela_mlm@hotmail.com); FRAN\u00c7A, D.C.C.; AGUIAR, S.M.H.C.A.MIYASAKI, M.L. ; TAKESHITA, E.M.; CASTRO, L.P.; SASSAKI, K.T.; DELBEM, A.C.B. FAPESP .DANELON, M. of a dentifrice with low fluoride (F) content (500 \u03bcg/g) would provide a similar effect to that of a standard dentifrice (1100 \u03bcg F/g). In this crossover double blind study, 9 volunteers, wearing acrylic palatal appliance containing 4 enamel bovine teeth, were subjected to 4 treatment groups: placebo (negative control), dentifrice with low-F, dentifrice with low F and 1% TMP and a dentifrice with 1100 \u00ecg F/g (positive control). During the experimental period (14 days each), test dentifrices were applied 2x/day, and a 20% sucrose solution was applied 6x/day by being dripped on the blocks. After each phase, surface microhardness was assessed to calculate the lesion progress (\u25b3KHN), and F, calcium (Ca) and phosphorus (P) present in enamel were also measured. The results showed that the dentifrice supplemented with F and 1% TMP showed the lowest \u25b3KHN (p<0.05). The order of effect in reducing \u25b3KHN was dentifrice with low F and 1% TMP > positive control > dentifrice with low-F > placebo. Regarding F and Ca in enamel there were no differences between dentifrice with low-F and TMP and positive control (p>0.05), but they were different when compared to dentifrice with low F (p<0.05). It is concluded that the addition of 1% of TMP to the 500 \u03bcg F/g dentifrice allowed a similar effect as compared with a standard dentifrice in this in situ model.The aim of this 078mjmoretto@terra.com.br); BERNAB\u00c9, P.F.E.; GOMES FILHO, J.E.; DEZAN JR, E.; NERY, M.J.; OTOBONI FILHO, J.A.MORETTO, M.J. were used for standardization of the surgical site, after root-end resection, lesion curettage, preparation of the root-end cavities with ultrasound and retrofilling with mineral trioxide aggregate. The 48 sites were divided as follows: Group 1 - filled with blood clot; Group 2 - filled with blood clot and covered with membrane; Group 3 - filled with bovine bone; Group 4 - filled with bone bovine and covered with membrane. The results showed that the inflammatory infiltrate and the periapical healing process were similar in all groups. It was concluded that the use of membranes and bone graft materials isolated or associated in apical surgery did not alter the periapical healing process.079marciobaena_5@hotmail.com); RODRIGUES, K.; BAGATELI, J.C.E.; KAMEI, N.C.STEFANELI, M.A.B. Project of the State University of Maring\u00e1. Bulging of the mandibular cortical was clinically observed. Radiographically there was an unilocular radiolucent lesion with sclerotic well defined margins. Taking into account these features, the first diagnosis hypothesis was residual radicular cyst, followed by odontogenic keratocyst tumor. The definitive diagnosis was established after histological analysis, which is essential if considering that the exact determination of the microscopic variations of this entity is closely related with its different recurrence rates and aggression. Considering the pathologist's judgment and the clinical and radiographic findings, the diagnosis of odontogenic keratocyst tumor was established.080marcio_vnv@hotmail.com); BRAMANTE, C.M.; BERNARDINELI, N.; GARCIA, R.B.; MORAES, I.G.; ZAPATA, R.O.VELOSO, M.V.N. . CLSM analysis of laboratory infected dentin showed no or sparse colonization of the root canal walls. In vivo infected dentin was characterized by severe colonization of root canal walls by bacterial biofilms. In all cases, the presence of bacteria in the dentinal tubules, in vitro or in vivo, was a common finding. It was concluded that in vitro infected dentin differed from in vivo infected dentin.The aim of this study was to compare the infection pattern of Enterococcus faecalis infected dentin under laboratory conditions and in a canine model. Five cylindrical dentin specimens were infected with Enterococcus faecalis in BHI for 21 days. For the 081marcoviniciosqueiroz@hotmail.com); SILVA, G.R.; SANTOS-FILHO, P.C.F.; CABRAL, F.C.; MARTINS, L.R.M.; SOARES, C.J.QUEIROZ, M.V.M. . The guttapercha was removed resulting in a root canal with 10 mm width and 0.5 mm in diameter and a ferule with 0.5 mm thickness and 2 mm height was prepared. The roots of two reference groups were restored with cast post and core \u2013 CPC(G1) and fiberglass post \u2013 FGP(G2). In the other groups, root canals were overflared 9 mm deep, resulting in a canal with 3.5 mm diameter, and were restored with: CPC(G3), FGP(G4), FGP and accessory FGP(G5) and FGP rebased with composite resin(G6). The resin cement was used for luting procedures and the core was made with composite resin. All teeth were restored with complete metal crowns. Mechanical fatigue was performed with 3x105 cycles of 50 N. The fracture resistance (N) was measured at 135o. The data were analyzed with a 2-way ANOVA (2X2) comparing post systems (CPC or FGP) with the characteristics of root followed by the Tukey's test. After, one-way ANOVA and Tukey's test were employed to compare the types of restorative techniques. Failure mode was classified as favorable or catastrophic. The results were (N): G6:949.8\u00b1210.6A; G1:859.9\u00b1199.3A; G5:842.6\u00b1174A; G2:627.1\u00b1119.9B; G3:625.3\u00b1164.3B; G4:620.2\u00b1164.2B. Statistical analysis showed that CPC decreases fracture resistance and increase catastrophic failures in weakened roots. Fiberglass post associated with composite resin or with accessory fiberglass posts seems to be more indicated as an alternative to cast post and core in weakened roots because of the lower risk of catastrophic failures.082marcos_palone@hotmail.com); DANELON, L.B.F.; HADDAD, M.F.; PESQUEIRA, A.A.; GOIATO, M.C.PALONE, M.R.T. may be of articular or muscle origin. The TMDs of muscle origin may be diagnosed by a detailed clinical examination, comprising physical examination with palpation of articulations and muscles of the head and neck. These tmds have a multifactorial etiology, involving predisposing, precipitating and perpetuating factors. They may be classified as protective co-contraction; local muscle sensitivity; myospasm; myofascial pain; centrally mediated chronic myalgia; and fibromyalgia. The therapeutic options include the placement of occlusal plates, massage, physical therapy, ultrasound, laser, electric currents, and application of botulin toxin.083arruda_cristina@yahoo.com.br); SANGALLI, J.; GAETTI-JARDIM JR, E.ARRUDA, M.C.V. ; OLIVEIRA, C.; CAPELOZZA, A.L.A.MADEIRA, M.F.C. ; MARTINS, C.M.; SALLES, C.L.F.VIANNA, M.F.O. ; ROMANELLA, D.C.; REGIS, R.R.; SOUZA, R.F.DELLA VECCHIA, M.P. (Maria Paula Della Vecchia The masticatory ability (MH) of complete denture wearers is an important aspect of life quality related to oral and systemic health, and can be influenced by factors like ridge height. The aim of this study was perform a preliminary survey on masticatory ability of conventional complete denture wearers through a subjective approach and analyze the association degree among this variant and the ridge height. Through a questionnaire translated from an English version, the masticatory ability was evaluated in 15 patients treated with bimaxilary mucous complete dentures. The mandibular bone height was measured (mm) using the patient's panoramic radiograph obtained before the prostheses installation, in the following regions: 10 mm from symphysis, on the mental foramen and between the mental foramen and mandibular ramus. All the measurements were taken by the same examiner and the medium of both sides was used for the final analysis. An index of masticatory problems was obtained by counting of the negative meaning answers attributed to questions 1 to 3, 5 to 8, 10 and 11. From 0 (any problems) until 11 (extremely impaired MH), the median and mode were 5.5 and 5, respectively. The mean ridge height was 31\u00b18mm. The Spearman correlation coefficient between MH and the mean ridge height was weak and without statistical significance . It was concluded that there is no relation between the subjective perception of MH in conventional complete denture wearers and the ridge height. A great variance was found for MH, although the clinical similarity among the studied cases. It points to an important influence of the subjective factors, in contrast with the commonly observed normative parameters.087cliciaribeiro@foa.unesp.br); HILDEBRAND, M.C.; CIESIELSKI, F.I.N.; VIEIRA, E.M.M.; GAETTIJARDIM JR, E.RIBEIRO, C.P. ; REINO, D.M.; GRISI, M.F.M.; SOUZA, S.L.S.; MAIA, L.P.CRIVELENTI, M.D. (Mariana Dassie Crivelenti The application of enamel matrix proteins (EMD) (Emdogain) promotes clinical and histological benefits on regenerative treatment of infrabone defects. However, in large defects, its semi-fluid consistency prevents the maintenance of space for bone deposition. The combination of EMD with a graft material can solve this problem. The mixture of \u00e2-tricalcium phosphate and hydroxyapatite (\u00e2 FTH) (bone ceramic) has been indicated for clinical use, due to good stability and porosity. The present clinical case has the purpose to show the use of EMD with \u00e2 FTH in the treatment of infrabone defects associated with multiple recessions. A male patient, 71 years old, attended the clinic of the Periodontics of FORP - USP for periodontal treatment and the presence of infrabone defects and multiple gingival recessions in upper posterior teeth was detected. After basic periodontal treatment, a regenerative treatment was planned. In the upper right sextant, a full-thickness flap was elevated through the mucogingival line to provide access for debridement of the defects and root scraping and smoothing. Upward mucogingival line, a split-thickness flap was made for later coronal slice. Root conditioning with 24% EDTA, neutral pH, was performed according to the manufacturer's instructions. Emdogain was applied on the roots and Emdogaim associated with bone ceramic was used to fill the defects. The flap was pulled coronally and sutured. Clinical and radiographic 6-months controls showed a reduction on probing depth and height of recessions. In conclusion, periodontal defects with favorable characteristics can be successfully regenerated using EMD associated with \u00e2 FTH, in addition to the capacity of the material to support the root coverage.089marieminagata@hotmail.com); HIDALGO, M.M.; SALLES, C.L.F.; MACIEL, S.M.; SERAFIM, D.; FRACASSO, M.L.C.NAGATA, M.E. assisted by the extension project \u201cTreatment of low risk pregnant women\u201d of the Specialties Outpatient Service of the Regional University Hospital of Maring\u00e1\u201d participated of the study. The data were collected with a semi-structured questionnaire, focusing on the main aspects of oral health . The obtained results, presented as percentages, showed that 65.82% of the pregnant women ate between the meals, of which 48% ate fruits and the others ate cariogenic foods. There was no correlation between the ingestion frequency and the daily brushing frequency. It was observed that 78% of the participants had already used fluoride, but 53% did not known its function. Considering the whole sample, 39% declared that caries is not transmissible and, when were asked about its etiology, 60% mentioned poor oral hygiene and 2.53% associated it with pregnancy. About the etiology of gingivitis, 37% related it with poor oral hygiene, 4% with pregnancy and the majority of them (59%) did not know the answer. These data demonstrate the importance of dentistry in the prenatal multidisciplinary assistance offered to pregnancy women, including educational, prevention and restorative measures, in the benefit of general health.090mariane_azuma@hotmail.com); LINS, S.M.; GAETTI-JARDIM JR, E.AZUMA, M.M. . Among the factors that further exacerbate the oral colonization by these yeasts are highlight smoking, alcoholism and the presence of complete or partial dentures. Thus, it is possible that the high frequency of detection of these fungi, particularly in patients with chemical dependency, will reflect the direct effects of drugs on the mucosa and, quite possibly, on the cellular immune response associated with mucosal surfaces.091mary.lonngo@hotmail.com); FERNANDES, L.A.; MURAKAWA, A.C. MARTINS, T.M.; GARCIA, V.G.; BOSCO, A.F.LONGO, M. ; DELGADO, R.J.R.; BRAMANTE, C.M.; MORAES, I.G.; GARCIA, R.B.; BERNARDINELI, N.SILVA, M.A.M. . Lateral condensation (LC); Tagger's hybrid (TH); MicroSeal (MS) and GuttaFlow (GF). Horizontal cross-sections of each tooth were made at the 2, 10 and 15 mm level from the apex. Digital images of the root canal areas were acquired using a stereomicroscope and evaluated using the Image Tool 3.0 software. Nonparametric statistical analysis was performed using the Kruskal-Wallis test (p< 0.05). In general, the gutta-percha filled area decrease significantly at the apical level in all the evaluated techniques (p<0.05). Also, all the filling techniques showed an increment in the sealer area at the apical level (p<0.05). Regarding the presence of voids, there was not statistical difference (p>0.05) among the techniques at the apical level. There was not a relationship between voids and the apical level of the filling except for the GuttaFlow technique that showed an increment of voids at the coronal third (p<0.05). MicroSeal and Tagger's Hybrid showed higher percentage of gutta-percha at the coronal and middle thirds. On the other hand, lateral condensation presented the highest percentage of gutta-percha at the apical third. However, a statistical difference (p>0.05) was not found. From the results of the present study it can be concluded that the quality of the filling decrease at the apical level independently of the filling technique used. Microseal and Tagger's hybrid performed higher gutta-percha filled area than the lateral condensation and Guttaflow technique at the coronal and middle third level (p<0.05). The presence of voids was similar among the evaluated techniques.093marinahegg@yahoo.com.br); CASSIS, M.A.; ALMEIDA, R.R.HEGG, M.P. ; MARSICANO, J.A.; MOURA, P.G.; SALES-PERES, A.C.; SALES-PERES, A.; SALES-PERES, S.H.C.MAPENGO, M.A.A. and relate to the latest data available (1978), considering that Mozambique has a natural system of fluoridation in the water supply. Eleven samples were collected in duplicate, directly from taps in homes of their municipalities. The concentration of fluoride from water samples was determined in duplicate, using the ion sensitive electrode (Orion 9609), coupled to a potentiometer . Data analysis was the descriptive analysis, performed using Student's t-test, adopting a significance level of 5%. The fluoride concentrations found in 1978 and 2008 were: Cabo Delgado (0.62 and 0.28 ppm), Niassa (0.18 and 0.98 ppm), Nampula , Zambezia / Quelimane , Tete / city (1.00 and 0.97 ppm), Sofala / Beira , Manica , Inhambane / city (0.00 and 0.05ppm), Gaza (0.01 and 0.06 ppm) and Maputo city (0.23 and 0.36ppm), respectively. The mean of fluoride concentration found in this study (2008) was 0.33ppmF, while the mean of the previous data (1978) was 0.31ppmF. There was no significant reduction (p = 0.83) between the concentrations of fluoride in water from 2008 and 1978 (p> 0.05). Data obtained from 1978 in the Tete province river detected 5.50 ppmF. In this province there was found high prevalence of dental fluorosis, although it was been made the defluoretation in recent years. It is concluded that there was no change in the level of fluoride in the water supply of the main municipalities of Mozambique. Fluoride concentration in water supply must be standardized in order to reduce dental caries prevalence without increase dental fluorosis prevalence in the region.095m_mantovani1@hotmail.com); TEIXEIRA, B.M.; NISHITA, P.; SILVA, C.O.MANTOVANI, M.B. ; MODENA, K.C.S.; NAHSAN, F.P.S.; REINATO, J.V.D.; SILVA, L.M.; FRANCISCONI, P.A.S.SPIN, M.D. with composite resin. A clinical sequence of composite insertion will be presented where both enamel and dentin will be reconstructed in their original thickness. Fractures of anterior teeth are clinical situations that demand scientific knowledge, technical ability and artistic sense for a successful treatment, which has the adhesive technology as a rapid and conservative alternative with excellent esthetic results.097melissalancia@gmail.com); GARIB, D.G.; LARA, T.S.; SILVA FILHO, O.G.; BERTOZ, F.A.LANCIA, M.; GERALDES, A.M.; GAETTI-JARDIM, E.J.MELO, M.E. ; DANELON, M.; DELBEM, A.C.B.; VIEIRA, A.E.M.; BRIGHENTI, F.L.MANARELLI, M. M. (Michele Mauricio Manarelli Fluoride foam offers a lower risk of fluoride (F) ingestion due to its consistency and because lesser amounts of the product is necessary to the application. The F kinetics of this product can interfere on enamel reactivity. However, there are no studies evaluating the ability of fluoride foam on remineralizing carious lesions. The aim of this study was to evaluate the ability of a neutral fluoride foam on remineralize incipient carious lesions. Enamel bovine blocks were selected by analysis of surface microhardness (SMH) and randomized in three groups: 1) control group (no treatment); 2) treatment with neutral fluoride gel and 3) treatment with neutral fluoride foam . The products were applied at the beginning of each phase. Ten volunteers used a palatal appliance containing four enamel blocks during three days. A wash-out period of four days was allowed between each phase. Two blocks were removed 30 min after the treatment to analyze calcium fluoride (CaF2) formed. The two blocks remaining were used to analyze SMH and CaF2 retained. The amount of CaF2 formed and retained were higher for the fluoride foam groups than for the fluoride gel group. It can be concluded that there are no differences in remineralizing incipient carious lesions after the use of fluoride foam when compared to fluoride gels.100michellemundim@hotmail.com); MARTINS, C.; SILVA, G.R.; MARTINS, L.R.M.; CABRAL, F.C.; SOARES, C.J.MUNDIM, M.P.C. ; NAHSAN, F.P.S.; GOMES, O.S.; MONDELLI, R.F.L.; ISHIKIRIAMA, S.K.; WANG, L.MICHIELIN, M.B. have shown promising perspectives. This category of dental material comprehends advantageous properties such as fluoride release, bonding to dental substrates, biocompatibility and similar coefficient of thermal expansion to that of the tooth structure. All these properties make GIC a versatile material that is clinically indicated for restorative, luting or lining procedures. The purpose of the present study was to explore the abilities of GICs and present new perspectives based on the modifications proposed since its introduction.102murillo_rs@hotmail.com); BOSCO, A.F.; MORAES, R.O.; BONFANTE, S.; LUIZE, D.S.; MURAKAWA, A.C.SANTOS, M.R. and 28 days (53.09% versus 68.35%). In conclusion, estrogen depletion and the systemic influence of nicotine, although did not prevent, delayed the healing process of autogenous bone block grafts in aged rats.103marioctba@hotmail.com); LEONARDO, R.T.L.; PALO, R.M.; IGLECIAS, E.F.LEONARDO, M.F.P. ; NATALICIO, G.L.; OLIVEIRA, P.G.F.P.; FIAMENGUI FILHO, J.F.; ALMEIDA, A.L.P.F.CUNHA, M.J.S. , with age ranging from 9 to 15 years old, presenting unilateral cleft lip and palate and subjected to secondary osseous graft were selected and divided into 2 groups. The experimental group was comprised by 31 patients irradiated with low level laser, dose of 4J/cm2, power 15mW and wave length 780nm, 10 seconds per site. On the placebo group (30 patients) LED was applied during 60 seconds. Both groups received 10 applications immediately, 24 and 48 hours after the surgery. Pain and edema were recorded in each application session and on the fifth day after the surgery. Statistically significant differences were not found between groups regarding pain and edema. Gender was also found non significant. In conclusion, the laser therapy, at least with the settings adopted, did not bring significant benefits in terms of pain and edema to the unilateral cleft lip and palate patients subjected to secondary bone graft. Further investigations are encouraged using different methods in order to verify the real role of this tool on the postoperative pain and edema of secondary bone graft interventions.105miroca@usp.br); URBAN, V.M.; CAMPANHA, N.H.; JORGE, J.H.; ALMILHATTI, H.J.; NEPPELENBROREK, K.H.BUENO, M.G. ; ARA\u00daJO, M.; SUKEKAVA, F.MISAWA, M.Y.O. were used. The premolars were carefully extracted and prepared for histological analysis. The acellular extrinsic fiber cementum at the most coronal portion of the root was described and histological measurements were performed. The results demonstrated that the acellular extrinsic fiber cementum in humans and dogs was morphologically similar. It was also showed that the number of attaching collagen fibers per 100 \u03bcm of root surface and the cementum growth rate (thickness growth) were similar between both specimens. The present study suggests that the dog may represent an adequate experimental model for the analysis of cementum formation following regenerative therapy.107na_jordao@hotmail.com); LARA, T.S.; SILVA FILHO, O.G.; BERTOZ, F.A.PARTEIRA, N.J.S. ; GORRERI, M.C.; FERNANDES-NETO, A.J.; NEVES, F.D.; MENDES, F.A.; BORGES, T.F.STRINI, P.J.S.A. (Temporomandibular disorders (DTM) are a set of signs and symptoms that affect the stomatognathic system and adjacent structures, generating mainly a pain able to radiate to inter-related structures. The purpose of this study was to evaluate the severity of TMD using the Helkimo Clinical Index (HCI) and Masticatory Performance (MP) in patients with TMD (n = 9) and compare it to the control group (CG) (n = 15), both with natural dentition and bilateral posterior occlusion. The MP tests were performed with the food simulator \u201cOptocal\u201d in portions of 17 cubes with 5.6 mm side and the subjects instructed to chew it for 20 (C1) and 40 (C2) masticatory strokes, monitored by a single examiner. The material collected was placed in a set of eight coupled granulometric sieves in a decresing order of opening. Then it was performed, sieving, material collection, drying and weighing of the contents of each sieve. It was calculated the geometric mean diameter of the chewed particle (MGD), obtaining a percentage of the MP index. The obtained data were subjected to the parametric Test t Student for independent samples (p <0.05). According to ICH, n = 8 presented severe DTM and n=1 showed light DTM. The results indicated statistically significant differences (p = 0000) both for GC and for the TMD group . We conclude that patients with painful symptoms tend to have its chewing function impaired, requiring a treatment able to restore their physiological functions, improving their chewing ability and promoting their life quality.109ns.macedo@yahoo.com.br); PAULO, L.F.B.; ROSA, R.R.; DURIGHETTO J\u00daNIOR, A.F.; CARDOSO, S.V.MACEDO, N.S. ; SARDINHA, M.C.; MARQUEZ, I.M.; FURTADO, L.M.; BATISTA, J.D.; ZANETTA-BARBOSA, D.OLIVEIRA, N.C.M. ; HIRATA, F.; REZENDE, M.L.R.; SANT'ANA, A.C.P.; GREGHI, S.L.A.; PASSANEZI, E.AMARAL, N.G. . Smear layer was present in 100% of the specimens of Control and PA groups; in 80% of those of the EDTA group; 33.3% of AT group and 0% of CA group. The mean percentage of area occupied by exposed tubules was: AC Group=0.12\u00b10.17%; AT=0.08\u00b10.06%; PA=0.03\u00b10.05%; EDTA=0.01\u00b10.01% and Control=0\u00b10%. Only CA group was statistically different from the other groups, with exception of AT group. The mean amount of exposed tubules within a standardized area was: AT=43.8\u00b125,2; CA=39.3\u00b137; PA=12.1\u00b116.3; EDTA=4.4\u00b17.5 and Control=2.3\u00b15.7. statistically significant difference was present when comparing the AT and Control groups, AT and EDTA, CA and Controls and CA and EDTA. It was concluded that citric acid and tetracycline seam to present greater potential for exposure and widening of dentinal tubules than the other agents. Clinical evaluations relating these properties to potential for collagen fiber reattachment would be focused on further studies.112natidecampos@gmail.com); NAGATA, M.J.H.; MESSORA, M.R.; POLA, N.M.; FURLANETO, F.A.C.; BOSCO, A.F.CAMPOS, N. and osteocalcin (OC) on bone healing in surgically created critical-size defects (CSD) in rat calvaria. 15 rats were divided into 3 groups: C (control), AB and AB/PRP. A 5 mm diameter CSD was created in the calvarium of each animal. In Group C, defect was filled with blood clot only. In Group AB, defect was filled with autogenous bone graft. In Group AB/PRP, defect was filled with autogenous bone graft combined with 100 \u00ecL of platelet-rich plasma (PRP). One L-shaped mark was made 2 mm anterior and one 2 mm posterior to the margins of the surgical defect. The marks were filled with amalgam. Their purpose was to allow identification of the center line of the original defect during laboratory processing and also to be used as references to locate the original bone margins of the surgical defect during immunohistochemical analysis. Animals were euthanized 30 days postoperatively. OP and OC immunohistochemical staining were performed. OP-positive and OC-positive cells (bone lining cells and osteocytes) were quantified within the confines of the total area of the original defect. Data were statistically analyzed . Group AB/PRP presented a significantly higher number of OP-positive cells than Group C (p < 0.05) and also a significantly larger number of OC-positive cells than Groups C and AB (p < 0.05). Within the limits of this study, it can be concluded that the methodology used led to a more objective and reliable quantitative analysis of the immunohistochemical data.113nat_pola@hotmail.com); NAGATA, M.J.H.; MESSORA, M.R.; CAMPOS, N.; FURLANETO, F.A.C.; GARCIA, V.G.POLA, N.M. (Nat\u00e1lia Marcumini Pola It has been suggested that autogenous bone (AB) grafts incorporate faster when combined with Platelet-Rich Plasma (PRP). This incorporation seems to occur as a result of the enhancement of osteogenesis process and resorption of non viable particles of bone grafts. This study histologically analyzed the effect of autogenous PRP on incorporation of AB grafts placed in surgically created critical-size defects (CSD) in rat calvaria. 30 rats were divided into 3 groups: Group C (control), Group AB and Group AB/PRP. A 5 mm diameter CSD was created in the calvarium of each animal. In Group C, the defect was filled by blood clot only. In Group AB, the defect was filled with 0.01 mL of AB graft. In Group AB/PRP, the defect was filled with 0.01 mL of AB graft combined with 50 \u00ecL of PRP. All animals were euthanized at 30 days post-operative. Histometric, using image analysis software, and histologic analyses were performed. bone area (BA) and the remaining bone graft particles area (RPA) were calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for statistical analysis . No defect completely regenerated with bone. Group AB/PRP (60.27% \u00b1 8.04%) had a statistically greater BA than Groups C (19.29% \u00b1 5.11%) and AB (49.93% \u00b1 7.01%) (p < 0.001). No statistically significant differences were observed between Groups AB and AB/PRP with regard to RPA (p > 0.05). Within the limits of this study, it can be concluded that PRP improved the incorporation of AB grafts, increasing the amount of new bone formed. PRP has not influenced the resorption of non viable particles of the AB grafts.114nativdesa@hotmail.com); CARVALHO, M.L.; SALIBA, N.A.; ARCIERI, R.M.SA, N.V. , despite the low wages. Already, amongst the professionals of superior level, the dentist presented high degree of dissatisfaction (833%) and the medical classroom, in its great majority, showed (71.4%). It was concluded that most of the professionals that work in the Health Family Program have demonstrated interest and likeness with this program, in spite of the exposed dissatisfaction degree by some groups of professionals. It was also evident the importance of acknowledging subjective factors for the optimization of the dynamics of the work in the health field.115neiandrogalvao@gmail.com); RODRIGUES, M.T.V.; ALEIXO, R.Q.; CUNHA, F.J.P.; COSTA, G.V.C.; COSTA, M.R.S.N.GALV\u00c3O, N.S. ; FLORIAN, F.; TRINDADE, P.A.K.; HOCHULI-VIERIA, H.NOGUEIRA, L.M. . Management of mandibular fractures with transosseous wires has largely been replaced with the techniques of rigid fixation. Before rigid fixation became popularized, transosseous wires were used to maintain fracture fragment reduction in combination with MMF (maxillomandibular fixation). Rigid fixation techniques in the dentate patient begin with fixation of the occlusion. MODUS\u00ae TriLock\u00ae is a new generation multidirectional and angular stable fixation system for maxillofacial surgery. The purpose of this study is to demonstrate the advances of this new system that allows locking screws to be fixed in the plate within a freely selectable range (\u00b1 15\u00b0) in mandible fractures. This study used materials found in the literature. The spherical three-point wedge-locking creates a connection between the head of the screw and the plate hole which is stable in angle and axial plane. It can be concluded that this system provide a satisfactory stability of the fracture reduction.117PINI, N.I.P.; UBALDINI, A.L.M.; MARCHI, L.M.; GIRARDI, A.R.; PASCOTTO, R.C.Congenitally missing maxillary lateral incisors are commonly associated with an asymmetric smile and disharmony dental facial. The orthodontic space closure with posterior recountouring of the canines and premolars in lateral incisors and canines, respectively, is one of the alternatives of treatment for these cases. The purpose of the present assignment was to show the interdisciplinary approach between Orthodontics and Restorative Dentistry in the esthetic and functional rehabilitation in cases of maxillary bilateral lateral incisors agenesis. A female patient JH, 30 years old, looked for dental treatment, complaining of the absence of her maxillary lateral incisors. Based on the suitable indications, the treatment option was the movement of the canines and premolars to mesial and subsequent recountouring of these teeth with esthetic materials. Right before the bracket attachment, the cusp tips, and buccal and proximal faces of the canines were reduced. Flattening of the buccal face of the canines permitted attaching specific brackets to afford the movement of these teeth with adequate clinical crown torque. In this phase, besides the movement, the gingival zenith was aligned, with canine extrusions and premolar intrusions, and the torques and angulations of \u201cnew\u201d lateral incisors and canines were adjusted. For a better distribution of space and adequacy of dental ratios in the restorative stage, a diastema between the central and lateral incisors was maintained for posterior closure with composite resin. After conclusion of the orthodontic treatment, an esthetic treatment of the anterior teeth was initiated, with bleaching for color adjustment and use of composite resins for cosmetic recountouring. The results of combination techniques were highly satisfactory concerning the esthetic principles and the patient's expectation. The integrated and multidisciplinary planning of the present case, involving Orthodontics and Restorative Dentistry, is of great value for esthetic and functional rehabilitation of the patients with lateral incisor agenesis.118lailaioliveira@hotmail.com); NORITOMI, P.Y.; KEMMOKU, D.T.; MARTINS, L.R.M.; SOARES, C.J.; SOARES, P.V.OLIVEIRA, L.K. , O-occlusal, disto-occlusal-OD, MOD-mesio-occlusal-distal, MOD + A endodontic access, TE- endodontic treatment and CR - composite resin restoration. The biomechanical behavior of the teeth was analyzed in a qualitative and comparative by computer simulation to analyze the stress distribution (finite element method). It was observed that the removal of tooth structure favors higher accumulation of stresses within the structure, and that the pulpal wall and marginal ridges were essential for reinforcement of the preparation.119paminotti@yahoo.com.br); BRAMANTE, C.M.; BRAMANTE, A.S.; GARCIA, R.B.; MORAES, I.G.; BERNARDINELI, N.MINOTTI, P.G. ; NAHSAN, F.P.S.; SILVA, L.M.; MODENA, K.C.S.; FRANCISCONI, L.F.; MONDELLI, R.F.L.RUSSO, P.D. , shade A1 enamel and A1 dentin. This case copied in details the anatomy, as well as chromatism and texture of natural teeth, providing results that guarantee satisfaction, harmony and perfection for the patient.121paulagpessoa@yahoo.com.br); BARBOSA, K.T.; CUNHA, M.J.S.; FIAMENGUI FILHO, J.F.; NATALICIO, G.L.; ALMEIDA, A.L.P.F.OLIVEIRA, P.G.F.P. , reestablishing periodontal health.122paulak.odonto@gmail.com); MESSORA, M.R.; NAGATA, M.J.H.; FURLANETO, F.A.C.; GARCIA, V.G.; BOSCO, A.F.JORGE, P.K. ; MURAKAWA, A.C.; FERNANDES, L.A.; MARTINS, T.M.; OKAMOTO, R.; BOSCO, A.F.FALEIROS, P.L. , on healing process of autogenous bone block grafts in young and aged rats, through the immunolocalization of the PECAM-1. 96 female Wistar rats were used: 48 3-month-old and 48 12-month-old rats divided in two subgroups: Ovx, subjected the ovariectomy surgery and Sham, subjected to the same surgical procedure without the removal of the ovaries. After 30 days of Ovx or \u201csham\u201d operation, all animals received autogenous bone block graft in the jaw, harvested from the calvaria. The animals were euthanized in 7, 14 and 28 days postoperatively. The specimens were subjected to histometric and immunohistochemistry analysis. This was accomplished in a semi-quantitative way, to analyze the immunolocalizations against PECAM-1, evaluating the interference of the estrogen in this process. The PECAM-1 immunolocalizations were more intense in the Sham subgroups, being more evident at 14 days when compared to Ovx subgroups, which presented fewer demarcations independently of the age. Comparing young and aged female rats, it was noticed more intense immunolocalizations in the first group. Within the limits of this study, it may be concluded that estrogen depletion affects the initial process of angiogenesis negatively.124paulanishita@hotmail.com); BISPO, C.G.C.; JUNIOR, J.C.B.S.; MAGGIONI, B.T.; OZELAME, M.L.; SOBRINHO, E.M.NISHITA, P.M. exhibited golden proportion, two female and one male smile. None of the seventeen smiles that composed the non-beautiful group exhibited golden proportion. The divine proportion, probably, is considered more frequently in smiles considered beautiful by subjective criteria and is more common in female smiles.125paulapprimo@hotmail.com); SPADA, L.G.; SOUZA, R.S.PRIMO, P.P. ; HAYACIBARA, R.M.; ROCHA, A.L.; CANDIDO, A.G.; CANDIDO, G.C.; MAIO, R.C.SILVA, P.V.R. ; PINELLI, F.V.; CURY, J.V.; CHIQUETO, K.PEREIRA, P.F.J. ; ROCHA, F.S.; BATISTA, J.B.; SILVA, C.M.; GONDO, R.M.; MELO, P.E.C.PEREIRA, A.L.B. ; TERADA, R.S.S.; HAYACIBARA, M.F.; GRACIANO, A.X.; NAGATA, J.Y.PERON, R.A.F. (Rodrigo Aparecido Flausino Peron Photodynamic therapy (PDT) is a therapeutic modality that combines the use of a photosensitive compound and light to cause cell death. More than 4000 years ago the Egyptians began the therapy, through the ingestion of plants and exposure to sunlight to treat diseases such as vitiligo. The PDT as a technique and therapy, however, began to be used with systematic science only recently. It assumes that the interaction of light of wavelength appropriate compound with a non-toxic and result in oxygen reactive species such as singlet oxygen, capable of inducing the non viability cells. The purpose of this work is to present the current stage of photodynamic therapy in many fields of Dentistry, and their applications in cariology. For this, a literature review was done on national and international databases in the last 10 years. It was found that PDT is studied particularly in the fields like stomatology, endodontics, periodontics and dentistry. Especially for the last two, which depend on a biofilm, and through the elimination of that by PDT will result in the removal of the causative agents of oral diseases more prevalent and incident. There are different photosensitive being investigated, with different combinations of light sources. The photogem, the methylene blue, ortho-toluidine blue, Rose Bengal, erythrosine, chloride, phenothiazine, hematoporphyrin as photosensitive compounds in different concentrations; and laser, the LED, tungsten filament, and even the white light as light sources, at different times of application (from 5 seconds to 30 minutes) and power (11 to 450 mW) present themselves as possibilities for treatment. The PDT in Dentistry is a promising alternative of treatment and research in this field should expand in the short term.130rodolfoanchieta2@hotmail.com); MARTIN JUNIOR, M.; ANCHIETA, R.B.; ARCHANGELO, C.M.; ROCHA, E.P.; FREITAS JUNIOR, A.C.PITA, D.S. using three-dimensional finite element analysis (FE). 4 FE models (M) were developed in Solidworks 2007: Mc - representation of a specimen of dentin (41x41x82 \u00ecm) restored with composite resin (RC), showing the adhesive layer, hybrid layer (HL), TAGs, peri-tubular dentin, intertubular dentin in order to simulate simulating the HL according to the total-etch adhesive system; Mr - similar to Mc, with lateral branches of the adhesive; Ma \u2013 similar to Mc, without TAGs and showing the \\\u201dsmear plug\\\u201d in order to simulate the environment for the self-etching adhesive system; Mat \u2013 similar to Ma, with TAGs. The models were considered isotropic, homogeneous and linearly elastic and numerical analysis was performed in ANSYS Workbench 10.0 to obtain the maximum principal stress (\u00f3max) after application of a tension force of 0.03N perpendicular to the surface of the RC. The botton of all models was fixed in x, y and z axis. The highest \u00f3max in HL was observed in the total etching system. The lateral branches increased the \u00f3max in HL. The TAGs had a little influence on the stress distribution in self-etching system. The HL for the total-etch system showed \u00f3max higher in comparison with the self-etch system. The presence of TAGs increased the \u00f3max in the HL for the total-etch system.131pri_ayub@yahoo.com.br); SILVA FILHO, O.G.; LARA, T.S.; OHASHI, A.S.C.; PICCOLI, V.D.AYUB, P.V. ; FERNANDES, P.G.; CRIVELENTI, M.D.; TABA JUNIOR, M.; REINO, D.M.ROMUALDO, P.C. ; LUCAS, N.M.; PASCOTTO, R.C.; RIGOLON, C.J.; SILVA, R.S.; MELO, M.P.PUPIM, D. , physical agents (occlusion) and mechanical agents (toothbrush). Erosion is a non bacterial pathological loss of tooth structure, induced by chemical processes. The loss during the physiological masticatory movements is called dental attrition, which is exacerbated by parafunctional habits such as bruxism, accelerating the physiological process of tooth wear. The aim of this paper is to report the case of a patient who had severe anterosuperior tooth wear, with a multifactorial etiology. The acid diet and parafunctional habit caused the loss of tooth structure in the buccal and incisal surfaces, compromising the esthetics of the smile. After the bleaching procedure, performed using 35% hydrogen peroxide activated by a LED/laser light source, a cast model was obtained in which the esthetic and functional reconstruction was planned by waxing the worn surfaces. From the waxed model, we obtained a silicon guide that helped building the direct composite resin restorations. Finally, an occlusal splint was fabricated to protect the restorations.134rafaeldesouza87@gmail.com); GUEDES, A.P.A.; OLIVEIRA, F.G.; MACHADO, L.S.; SUNDFELD NETO, D.; SUNDFELD, R.H.SOUZA, R.G. ; MAGALH\u00c3ES, A.C.; HON\u00d3RIO, H.M.; MACHADO, M.A.A.M.; BUZALAF, M.A.R.; RIOS, D.REBELATO, R. (Rafael Rebelato FAPESP (Proc. 2006/07260-4)in situ study showed differences on the erosive potential of a regular and a light cola drink on enamel. However, no information is available about the erosive potential of regular and light drinks in vitro. Thus, this in vitro study aimed to compare the erosive potential of different regular and light beverages on enamel. Bovine enamel samples were divided into 7 groups (each n=10) and immersed in the regular or light/sugar zero version of the following drinks: Coca-cola, Guaran\u00e1 and Sprite. Half of the surface of the specimens was coated with nail varnish for reference. The samples were subjected 4 times daily to erosive challenges (30 mL beverage/sample) for 2 minutes at room temperature. Between the erosive challenges, the samples were immersed in artificial saliva (30 mL/sample) for 2 h. In each day, after the pH-cycles the samples were stored in artificial saliva. At the 5th day, the enamel surface alterations were measured by profilometry (\u03bcm). The data were analyzed by ANOVA followed by Tukey's test (for cola drinks) and unpaired t test (for other beverages) (p<0.05). Light coke (0.52\u00b10.19) provoked a similar enamel wear compared to zero coke (0.54\u00b10.17), and both caused less enamel loss compared to the regular version (2.15\u00b10.65). On the other hand, regular sprite (1.17\u00b10.36) provoked lower enamel wear compared to zero version (2.25\u00b10.75). Regular (1.06\u00b10.36) and light Guaran\u00e1 (1.02\u00b10.26) provoked similar wear. This in vitro study showed that the light and zero cola drinks showed less erosive potential, however this was not observed for the zero versions of guaran\u00e1 and sprite. Financial support: FAPESP (Proc. 2006/07260-4).A previous 136rafaelacarolin@hotmail.com); BUENO, M.G.; MARSICANO, J.A.; SALES-PERES, A.C.; MOURA, P.G.; SALES-PERES, S.H.C.BONATO, R.C.S. (Rafaela Carolina Soares Bonato FAPESP (proc. 2008/00240-3) e CNPQ (proc.109.160/2007-0)in vitro, the effect of an experimental gel containing iron and/or fluoride on the erosion of bovine enamel. For standardization of the blocks (n=80), a previous selection of specimens (4X4 mm) for the initial microhardness was made. The blocks were randomly allocated to four groups of 20 samples each, due the treatment: G1 ; G2 ; G3 and G4 . The gels were applied and removed after 5 min. Then, the blocks were subjected to six cycles, alternating re- and demineralization (only one day). Demineralisation was performed with the beverage Coke\u00ae and remineralisation with artificial saliva (1 h). The effect of erosion was measurement by wear analysis (profilometry). Data were analyzed by ANOVA and Tukey test to individual comparison (p<0.05). The gel contained only iron showed that the better effect (G3: 0.47\u00b10.11 \u03bcm), however there was no differences when compared to others gels . There was significant statistically reduction in enamel wear when it was used experimental gels and compared to control (p<0.001). It concluded that the gels containing iron with or without fluoride can work lin a preventive form against erosion, reducing the loss of tooth surface, in vitro.The aim of this study was to evaluate, 137raqueparra@bol.com.br); DIOGO, F.S.F.; AGUIAR, S.M.H.C.A.SILVA, R.B.P. (Raquel B. Parra da Silva Diabetes mellitus (DM) is a metabolic disorder of multiple etiology characterized by chronic hyperglycemia with disturbances in the metabolism of carbohydrates, fats and proteins, resulting from defects of insulin secretion, the same action or both. The three types of diabetes are type 1, type 2 and gestational. The first type 1 diabetes results from destruction of beta cells of the pancreas and has a tendency to ketoacidosis. Includes cases arising from auto-immune diseases and those in which the cause of the destruction of beta cells is not known. Type 2 diabetes results, in general, of varying degrees of insulin resistance and relative deficiency of insulin secretion. Most patients have excess weight, and ketoacidosis occurs only in special situations, such as during serious infections. Oral complications may include: gingivitis, periodontal disease, the salivary gland dysfunction, xerostomia, oral susceptibility to infections and changes in taste. This presentation aims to emphasize the routine and emergency dental procedures for patients with DM, specially the child care. Well-controlled and uncomplicated diabetics can be treated in a similar way to non-diabetics, for most routine procedures. The dentist must be in communication with the physician to promote and maintain the welfare and quality of life of the diabetic patient.138raquelmidena@yahoo.com.br); VIVAN, R.R.; DUARTE, M.A.H.; MORAES, I.G.; GARCIA, R.B.MIDENA, R.Z . Polyethylene pipes were used with 1,0 mm of internal diameter and 10.0 mm of length, with only one of the extremities open, they were filled with cements and immediately immersed in test tubes contend 10 mL of deionized water, where they remained during the experimental period. Assessments were taken at 3, 24, 72 and 168 hours, always renewing the deionized water to the end of each period. The reading of pH was done using the pHmeter and the calcium ion release by means of one spectorphotmeter atomic absortion. The values were statistically compared using the Kruskal-Wallis and Miller tests. In relation to pH, the results demonstrated that in the experimental periods of 3 and 24 hours, the highest values were reached by associated clinker to bismuth oxide and calcium sulphate. At the time interval of 72 and 168 hours, the highest pH values were reached by the MTA Bio. In relation the calcium ion release, at the interval time of 3 hours associated with clinker to bismuth oxide and calcium sulphate presented the highest value. At 24hours, MTA Bio and the Clinquer they were superior. In the other periods, MTA Bio presented the highest values. It was concluded that all cements presented alkaline pH and calcium release ion in all periods, with trend of reduction in the final periods.139zanatta.rayssa@gmail.com); DURIGHETTO J\u00daNIOR, A.F.; DE PAULO, L.F.B.; ROSA, R.R.; SANTOS, V.P.F.ZANATTA, R.F. causes mobilization of calcium from bone and when a large quantity was captured can cause a generalized bone dystrophy with increased possibility of fractures at the minimum effort. Moreover, it could be responsible for the formation of uni or multiloculated areas completed by tissue richly vascularized and with several multinucleated giant cells characterizing the \u201cbrown tumor\u201d. The clinical aspects of interest for dental clinics are the disappearance of the lamina dura around the teeth roots (bone dystrophy) and extensive osteolytic lesions in the jaws. The mandible is the predominantly affected site in the maxillofacial area. Maxillary involvement is rare. We present an 84-year-old female patient complaining of two painful bilateral nodular sessile elastic lesions in the alveolar ridge in maxilla. The patient's medical history was unremarkable. The initial clinical and radiological evaluation indicated a peripheral giant cell lesion or brown tumor of hyperparathyroidism. An incisional biopsy was performed and a cell population consisting of rounded or spindle-like mononucleate elements, mixed with a certain number of multinucleate giant cells, among which recent hemorrhagic infiltrates and hemosiderin deposits were evident. The biopsy analysis and the total serum PTH levels (153pg/mL) provided the diagnosis of hyperparathyroidism presenting as a brown tumor. An ultrasound of the region was unremarkable as well as the other biochemical studies and, based on these findings, a diagnosis of secondary hyperparathyroidism was raised. The aging of the skin and no exposure to sunlight may decrease the synthesis of vitamin D and calcium absorption leading for a hyperparathyroidism. This case thus highlights the importance of another facet to the myriad of presentations associated with hyperparathyroidism.140paulovsoares@foufu.ufu.br); REIS, B.R.; PEREIRA, F.A.; SIMAMOTO, V.R.N.; SOARES, C.J.; SOARES, P.V.REIS, G.R. complaining of: muscle pain, difficulty in chewing and change in shape of teeth. During clinical examination, it was observed a reduction in the vertical dimension of occlusion due to loss of posterior teeth and accentuated tooth wear. To restore the function, a record was performed with facial arc for observation of relationship and construction of removable provisional prostheses allowing occlusal stability in a later moment. In this way, sufficient space was gained for further placement of composite resin restorations of improving the esthetics of the patient. Composite resin was the material of choice for restoring the shape of the anterior and posterior teeth because it provided a fast treatment with good esthetics and low cost. The interdisciplinary restorative technique employed reestablishing function and comfort of the stomatognathic system, resulting in a harmonious smile with better quality of life for the patient.141renataborgesrodrigues@hotmail.com); ROSCOE, M.G.; SILVA, G.R.; SOARES, P.B.F.; MAGALH\u00c3ES, D.; SOARES, C.J.RODRIGUES, R.B. ; DA LUZ, N.; BRANCO, C.A.; BUSO, A.M.; FONSECA, R.B.HAAB, R.I. . The cast posts were not removed due to root fracture risks. After that, metal-free ceramic crowns (Empress Esthetic) were cemented with Scotchbond and dual resin cement Rely-X. The treatment resulted in esthetic improvement of the region of darkened appearance and gingival contour, although the prognosis cannot be predicted due to gingival characteristics and maintenance of cast posts. In conclusion, the use of copper-aluminum cast posts should be avoided, but when their use or maintenance is necessary, metal-free ceramic crowns can be an alternative to avoid the unaesthetic staining generated by metal oxidation.143renatobarjona@yahoo.com.br); SANTOS, V.P.F.; BATISTA, J.D.; RAMOS, L.M.A.; DURIGHETTO, A.F.MIRANDA, R.B.M. ; BOSCO, A.F.; MURAKAWA, A.C.; FERNANDES, L.A.; GARCIA, V.G.; MARTINS, T.M.MORAES, R.O. in the repair of autogenous bone block grafts in the jaw of rats. They were used 48 mice that divided in two groups: Group C (Control Group n=24) and Group GL (Laser Group n=24). All animals received autogenous bone graft installed in the jaw, in the close area to the angle, tends as area donor the parietal bone of the calvaria. The animals of GL received treatment with the laser of low intensity in the surgical bed, before the fixation of the graft; while GC didn't receive any treatment. The animals were subjected to euthanasia in the periods of 7, 14 and 28 days after surgical procedure. In 7 days was observed presence of little organized connective tissue in both groups with larger angiogenesis in GL. To the 14 days it was found connective tissue developed in GC and GL, with larger bone formation and angiogenesis activity in GL. To the 28 days the osteogenesis was intense in both groups. In GL the recipient bone-graft interface was partially filled by newly formed matrix bone, establishing a union of the graft to the receiving bed. In GC, the interface was partially filled by newly formed matrix bone, with areas of connective tissue between the graft and the recipient bed. Histometrically the newly formed bone was significantly larger in GL (60.11% \u00b1 8.57%) that in GC (44.03% \u00b1 10.21%) at 14 days. At 28 days, there was was no statistically significant difference between groups GL (74.46% \u00b1 9.11%) and GC (67.81% \u00b1 8.02%). Within the limits of the present study, LLLT promoted a significant photobioestimulator effect on the process of repair of bone block grafts installed in the jaw.145robertamaues@yahoo.com.br); ALMEIDA, O.P.; ANDRADE, G.C.; VARGAS, P.A.; NAVARRO, C.M.AZEVEDO, R.M.C. is a rare immunomediated blistering mucocutaneous disease with early oral lesions potentially spreading to other mucous membranes and skin. Mucosal lesions may be the sole sign for an average of 5 months before skin injuries develop, or they may be the sole manifestation of the disease. Mean age of PV onset is 50 \u2013 60 years. The oral lesions are characterized by erosions secondary to the rupture of flaccid blisters. The soft palate, buccal mucosa and lips are the most affected anatomical region of the mouth. We report a case of a 58-year-old man with a chief complaint of painful oral ulceration during previous 3 months. The patient medical history revealed malaria 4 years ago. The oral examination showed multiple vesicular and erosive lesions on lips, hard and soft palate, buccal mucosa, alveolar ridge and tongue. The Nikolski's sign was positive. Two incisional biopsies on upper lip (erosive and vesicular areas) were taken. The microscopical examination showed acantholisis, intraepithelial cleft with Tzank cells, and basal cell layer attached to subjacent connective tissue. This histopathological pattern is typical for PV. The patient was referred to the Ophthalmologist and presently is under control with Predinisone (Meticorten \u00ae \u221215 mg/day). Since the oral lesions precede systemic involvement, we emphasize the importance of the dentist in the early diagnosis, improvement of prognosis and treatment of this disease.146ROSA, R.R.; ROCHA, M.A.; DURIGHETTO, I.L.; SARGENTI, S.; BARBOSA DE PAULO, L.F.; ZANATTA, R.F.Lipoid proteinosis (LP), also known Urbach-Wiethe syndrome, is an uncommon, recessively inherited genodermatosis characterized by deposition of amorphous hyaline material in different parts of the body, especially the skin, mucous membranes of the upper aerodigestive tract, and internal organs. Clinical manifestations of LP usually begin as a hoarseness and failure cry soon after birth or in the first year of life. However, other conditions may occasionally appear for few years later. Oral cavity is most extensively affected area by the disease and the main oral abnormalities include diffusive infiltration of white pea-size plaques and hardness of the tongue as well as inability to protrude it. In this report we describe the main aspects of a classical case of LP affecting a woman who presented with an unusual history of painful recurrent ulcerative lesions in her tongue since childhood, probable caused by a persistent and severe xerostomy, which had developed as a consequence of this genetic disorder.147granja31_chorito@yahoo.com); DUARTE, B.G.; DIAS-RIBEIRO, E.; ASTOLPHI, F.A.; SANT'ANA, E.; CAPELOZZA, A.L.A.RODRIGUES, V.L.O. ; DANIELETTO, C.F.; LIMA, J.P.G.; PASCOTTO, R.C.; UBALDINI, A.L.M.; NUNES, M.C.P.CARACANHA, R.B. ; BRAMANTE, C.M.; CAMPANELLI, A.P.; MORAES, I.G.; BERNARDINELI, N.; GARCIA, R.B.ZAPATA, R.O. . Periapical radiographs determined the presence of apical periodontitis and the dentin infection was verified using the acridine orange stain technique and confocal laser scanning microscopy (CLSM). Apical periodontitis was resent in all the root canals evaluated. CLSM analyses showed necroses of the dental pulp and dentin infection characterized by the presence of bacteria inside the dentinal tubules and the presence of bacterial biofilms in root canal walls.The aim of this study was to evaluate the ability of 150paraizo@gmail.com); CARVALHO, C.A.P.; NICODEMO, C.A.Z.; CARVALHO, F.S.; BUZALAF, M.A.R.; SALES-PERES, S.H.C.GARCIA, R.P. . Fluoride concentrations ranged between 0.03 and 0.50 \u03bcg F/mL. It was observed statistical difference in the fluoride concentrations among different lots of the same brand in 6 commercial analyzed. Manufactured soy foods analyzed in this study do not contribute separately to the risk for development of dental fluorosis, when reconstituted with non fluoridated water. However, the risk should be considered if these foods were reconstituted with fluoridated water, and the fact that the intake may occur several times a day, beyond other sources of fluoride consumed in this period. It was observed a wide variation in fluoride concentrations among different lots of the same brand, which reflects the necessity for standardization of the fluoride content in these foods.151MEDEIROS, S.A.S.; REIS, B.R.; CASTRO, C.G.; SOARES, C.J.; SOARES, P.V.; SANTOS-FILHO, P.C.F.The esthetic viability of restorative techniques involving ceramic associated to conservative aspect of adhesive procedures in different substrates, promotes an esthetic and functional rehabilitation of anterior teeth with extensive structural loss. This report presents a clinical case in which esthetic and functional rehabilitation of a patient with an unsatisfactory extensive restoration in an endodontically treated maxillary central incisor, mispositioned canine compromising the esthetics, and periodontally compromised tooth needing extraction. After extraction of the hopeless tooth and the mispositioned canine, the restorative procedures were initiated. The unsatisfactory restoration in tooth 21 was removed and the placement of a fiber glass post associated with core reconstruction with resin and In Ceram Alumina crown was the choice treatment. The space resulting from the extraction of tooth 24 was filled with an indirect adhesive denture associated with glass fiber reinforcement, reestablishing the function and esthetics. The diastema created after canine extraction was restored with resin. The esthetic of smile associated to functional rehabilitation, promoted great satisfaction to dentist and to patient.152sandra.hortense@yahoo.com.br); CARVALHO, F.S.; CARVALHO, C.A.P.; BASTOS, R.S.; XAVIER, A.; BASTOS, J.R.M.HORTENSE, S.R. compared by the Mann-Whitney test. Regarding the cause of dental caries, 46.38% of parents and 56.52% of teachers related to poor oral hygiene. Dental caries was considered a disease for 58.72% of parents and 78.26% of teachers. The brushing was supervised by 25.96% of parents at home and 69.57% of teachers after school lunch. For prevention of oral diseases, 22.55% of parents would take their children to the dentist and 39.13% of teachers would indicate the dentist and the adoption of good hygiene habits. The results did not show a statistically significant difference between the groups concerning the questions evaluated (p>0.05). The teachers had good knowledge of oral health, but the parents showed more limitations on the concepts related to dental caries and the importance of attitudes and preventive practices. The interaction of health professionals, teachers and parents can guide new practices and allow the spread of knowledge in oral health for preschool children.153sarateadoro@hotmail.com); PRUDENTE, M.S.; SILVA-NETO, J.P.; BARBOSA, G.A.S.; SIMAMOTO-JUNIOR, P.C.; NEVES, F.D.MARRA, S.T. through a vertical and horizontal fit analysis of the castable \u201cUcla\u201d abutment in the casting and soldering laboratorial stages, of the same clinical case. Four fixed prosthesis were built by each laboratory using abutments of the castable \u201cUcla\u201d type. The evaluation was conducted based on the photos obtained with a scanning electron microscope at 500x magnification. The results were analyzed statistically (p>0.05). The values in relation to the vertical fit/misfit, after casting, were 95.8% between 0 and 10\u03bcm in \u201cA\u201d, and 70.8% and 87.5% in \u201cB\u201d and \u201cC\u201d respectively. The results obtained in the present study, both in relation to the vertical and horizontal fit/misfit were more satisfactory when compared to previous studies, using the same abutments. However more, though more satisfactory, such results are still considered clinically worrisome.154re_scatolin@hotmail.com); OLIVEIRA, F.G.; PITA, D.S.; GUEDES, A.P.A.; MACHADO, L.S.; SUNDFELD, R.H.SCATOLIN, R.S. followed by composite resin Z350; group II received resin-modified glass ionomer Fuji II L.C. only. Group III was restored with the same resin-modified glass ionomer, but two layers of ScotchBond Multi-Purpose primer was applied first. The teeth examined before and 1 week after placement of the restorations. Preoperative sensitivity was present in 83.33% of the cases, and absent in the other 16.67% of the cases. After placement of the restorations, sensitivity was absent in 80% of the teeth, but still present in 20% of them. The results obtained suggested that non-carious cervical lesions restoration is an effective clinical procedure for controlling of the dental sensitivity. (Apoio: FAPESP).155crisyuri@msn.com); KAMEI, N.C.; TRENTO, C.L.SCHUTZ, C.Y.K. ; JANSON, G.; CHIQUETO, K.BARROS, S.E.C. ; REIS, B.R.; PEREIRA, F.A.; SVERSUT, R.; SOARES, C.J.; SOARES, P.V.SILAS, J.B.S. ; OLTRAMARI-NAVARRO, P.V.P.; NAVARRO, R.L.; CONTI, A.C.C.F.; ALMEIDA, M.R.; ALMEIDA, R.R.CHADI, S.F. ; GOMESFILHO, J.E.; RODRIGUES, G.; BERNAB\u00c9, P.F.E.; LODI, C.S.; GOMES, A.C.WATANABE, S. and \u00c2ngelus MTA\u00ae. These materials were placed in polyethylene tubes and implanted into dorsal connective tissue of Wistar rats for 7, 30 and 60 days. The specimens were prepared to be stained with hematoxylin and eosin or Von Kossa or not stained for polarized light. The presence of inflammation, predominant cell type, calcification, and thickness of fibrous connective tissue were recorded. Scores were defined as follows: 0, none or few inflammatory cells, no reaction; 1, <25 cells, mild reaction; 2, 25 to 125 cells, moderate reaction; 3, >125 cells, severe reaction. Fibrous capsule was categorized as \u201cthin\u201d when thickness was < 150 \u00ecm and \u201cthick\u201d at > 150 \u00ecm. Necrosis and formation of calcification were recorded. Results were analyzed statistically by Kruskal Wallis tests. Both materials \u00c2ngelus MTA\u00ae and CER caused moderate reactions at 7 days which decreased with time. The response was similar to the control at the 30th and 60th days with \u00c2ngelus MTA\u00ae and CER characterized by organized connective tissue and presence of some chronic inflammatory cells. Mineralization and granulations birefringent to the polarized light were observed with both materials. It was possible to conclude that CER was biocompatible and stimulated mineralization.160stefaniaabate@hotmail.com); LINS, A.S.; TOLEDO, H.B.; CIESIELSKI, F.I.N.; GAETTI-JARDIM JR, E.ABATE, S.P.A. attending a program for drug detoxification, in the city of Santa F\u00e9 do Sul, in comparison to a control group of non-dependent females presenting similar age and socioeconomic conditions. Socioeconomic conditions, history of consumption of licit or illicit drugs and patterns of association of these compounds, as well intra and extra oral examinations were carried out. Clinical parameters were subjected to multiple comparisons and dichotomous variables were analyzed by mean of non-parametric Mann-Whitney test. Of the 19 chemical dependent patients had generalized gingivitis, 12 had chronic periodontitis, 13 were periodontally healthy, while six wore complete dentures. The control group patients, 11 were generalized gingivitis patients, one had periodontitis, 36 were periodontally healthy, while two were complete denture users. Ischemia of palate mucosa was observed in most of drug users. The report of the occurrence of back pain, skin and respiratory infections, headache, fatigue, dyspnea, polyuria, xerostomia, tingling of the extremities, anemia, allergies, arthritis, polydipsia, occurrence of periodontitis, weight loss and impairment of the repair process were statistically more frequent in the group of patients with chemical dependence, compared with the control group. There was no statistically significant difference between groups in the oral hygiene standards.161sucristina@hotmail.com); PIERI, L.V.; HENRIQUES, J.F.C.; PINZAN, A.; JANSON, G.; FREITAS, M.R.PEREIRA, S.C.C. was associated with facial mask in the dentoskeletal Class III treatment. In the vertical growth pattern should wear a high-median headgear (IHG) for vertical control. The orthodontic mandibular expansion with Schwarz appliance upright the posterior lower teeth in the apical base creating a barrier avoiding RME relapse. Retention with an orthopedic or orthodontic removable appliance, associatted or not with fixed appliance, must be done for time based on the quantity of the obtained expansion in order to achieve treatement stability.162Naressi@fosjc.unesp.br); BARBIERI, A.A.; SCORALICK, R.A.; MAROTE, I.A.A.NARESSI, S.C.M. reviewed reports, traffic accident was the cause of facial involvement in 4.82% (588), with reports of dental involvement in only 0.63% (77) of these cases. The most affected facial region was the jawbone, the higher occurrence of dental injury was the fracture, accounting 9.01% of cases, and males as the most affected, representing 6.80% of cases. The most affected age group for females was between 16 and 24 years (2.21% of cases) and for males, between 24 and 32 years (1.87%). The proportion of facial injuries in the dental involvement suggests under-reporting, in addition to inappropriate use of nomenclature to describe the lesion, compromising the damage valuation and its consequences.163tamirisvallim@hotmail.com); MENEGHETTI, I.C.; GENNARO, G.; RODRIGUES, P.A.L.; MARCHESANO, L.H.; ASSIS, G.F.OLIVEIRA, T.V.Z. (Tamiris V. Z. de Oliveira Camellia Sinensis) acts on the control of the glycemic profile and body mass of normal and streptozotocin-induced diabetic rats. Forty male rats had diabetes induced by streptozotocin injection (50mg/kg body weight) and forty healthy male rats were maintained as control group. Diabetic and control groups received water or green tea treatment and then they had their weight and glycemic level analyzed at 15, 30, 60 and 90 days. The control group increased weight, while the diabetic group lost weight, irrespectively of green tea treatment or water intake. Blood glucose levels decreased in diabetic rats treated with green tea only at 15 days, while, there were not statistic differences in other periods when compared diabetic with control group. In conclusion, the Green tea showed a positive effect on the glycemic level in diabetic rats only at initial period of treatment, and did not confirm effects on the prevention of weight loss in diabetic animals.Diabetes Mellitus is the most common endocrine disorder. It is the result of a malfunction of insulin-dependent glucose and lipid metabolisms. Diverse diabetic experimental models have been used targeting an effective treatment. Purpose: The objective of this study was to investigate how the Green Tea (164varteahmed@hotmail.com); MAIA, L.P.; SOUZA, S.L.S.; REINO, D.M.MISKO, T.P. ; MARSICANO, J.A.; JULIANELLI, J.; SALES-PERES, A.; BASTOS, J.R.M.; SALES-PERES, S.H.C.SILVA, T.C. is increasing in incidence and prevalence, becoming a real public health problem. This study investigated the prevalence and severity of dental wear and the possible etiologic factors in patients with anorexia and bulimia nervosa treated at the Hospital das Cl\u00ednicas de Ribeir\u00e3o Preto \u2013 SP. The sample was formed by 60 patients, divided in two groups: experimental group (G-1) \u2013 patients with eating disorder (n=30) and control group (G-2) \u2013 patients attend in the same hospital, due to other causes (n=30). The occurrence of dental wear was evaluated by IDD index and an exploratory questionnaire about etiologic factors was applied. The analysis of the data was descriptive and analytical, using the Mann-Whitney test at a level of significance of 5%. There was a mean number of 19.93 worn teeth in G-1 and 23.4 in G-2. On severity, the involvement of dentin was identified 159 times in G-1 and 134 times in G-2 for anterior teeth, and 39 times in G-1 and 25 times in G-2 for posterior teeth. Among the etiological factors studied and tooth wear there was significant association with tooth clenching and grinding (p<0.05). There was no statistically significant difference between the studied groups. The conclusion is that patients with eating disorders present dental wear, with involvement of dentin that favors dental hypersensitivity.166thaimada@usp.br); RUBIRABULLEN, I.R.F.; DEZOTTI, M.G.; FERREIRA J\u00daNIOR, O.; CAPELOZZA, A.L.A.; CARVALHO, P.S.P.IMADA, T.S.N. (Tha\u00eds Sumie Nozu Imada Cone beam CT (CBCT) has changed the way we approach diagnosis and treatment particularly when anatomy of the maxillofacial complex is an important features, in particular for implant planning. Viewing the mandible in all three dimensions helps us extract the maximum information needed. The mental region may receive various surgical procedures including grafting procedures and the number of postoperative complaints has been rising, among them hemorrhage. Thus, the presence of neurovascular structures should be carefully assessed prior to surgery. The superior and inferior genial spinal foramina and their bone canal are situated in the midline of the mandible. In dissections, it was identified branches of the lingual artery and vein, lingual nerve, mylohyoid nerve altogether with branches or anastomoses of the sublingual and/or submental artery and vein, inside those foramina. This case discusses the contribution of CBCT images to the identification of the anatomic structures in the mental region. The patient was subjected to CBCT exam for a implant planning, even though the mental region was not the implant target, it was observed a variation in the trajectory of the bone canal inside the genial spinal foramina. The images revealed that the bone canal that accompanies the foramina had a curved trajectory inside the mental region connecting the mandibular lingual cortical to the mandibular base. The images seen in the panoramic radiograph could not suggest such trajectory for the bone canal, otherwise, the panoramic image showed as if there were a bone sclerosis in the mental region, which was proven not to be true in the CBCT images.167tvrizzo@gmail.com); BROSCO, V.H.; BRAMANTE, C.M.; MORAES, I.G.; BERNARDINELI, N.; GARCIA, R.B.CUNHA, T.V.R.N. . Ten additional roots were employed as control. The culture medium BHI was inoculated with the microorganism Enterococcus faecalis and placed in contact with the coronal portion of roots; the same sterile culture medium was placed in contact with the apical portion of roots. Leakage was evaluated daily, for 120 days, and was considered when the culture medium at the apical portion was rendered turbid. The roots were microscopically analyzed for evaluation of bacterial penetration into the root canals and dentinal tubules. In the leakage test, the Tagger's hybrid technique, exhibited the worst sealing ability. Root canals with 10mm of remaining obturation material presented better sealing than canals with 5mm. Microscopic evaluation revealed that the lateral condensation technique allowed lower penetration of bacteria into both root canals and dentinal tubules, followed by the Touch'n heat + Ultrafil, Microseal and the Tagger's hybrid technique. Root canals with 10mm of remaining obturation material presented similar bacterial penetration as root canals with 5mm.168thalestato@usp.br); SILVA, L.M.; MARTINS, L.M.; HANNAS, A.R.; FRANCISCONI, P.A.S.; WANG, L.PINTO, T.A. present the capacity to provoke collagen fibrils degradation, which may compromise the hybrid layer. Recently, it has been shown that chlorhexidine has a potential ability to inhibit MMPs that were activated after dentin conditioning in bonding procedures. This study aims to present some literature reports that attest this positive action. Based on thi evidences, a new clinical bonding protocol has been considered, which includes an aqueous chlorhexidine solution conditioning after phosphoric acid etching and rinsing. In addition, biocompatibility and toxicity of this product will also be discussed. According to this scenario, chlorhexidine seems to offer a great perspective in order to increase the longevity of adhesive restorations. This case report will show a restorative procedure following the protocol of use of chlorhexidine. After tooth preparation, etching was performed using phosphoric acid for 15 seconds in dentin and 30 seconds in enamel. Acid was completely rinsed off and 2% chlorhexidine digluconate was applied for 60 seconds, which was gently dried with absorbent material, followed by application of the adhesive system according to a moist-bonding technique, and restored incrementally with composite resin systems.169thiagoameba@hotmail.com); CARDOSO, C.L.; DAMANTE, J.H.; BARRETO, J.A.; TAVEIRA, L.A.A.MACHADO, T.A. ; SILVA-NETO, J.P.; PRUDENTE, M.S.; PRADO, C.J.; MUNDIM, A.R.; NEVES, F.D.CARNEIRO, T.A.P.N. . For this, fracture strength testing was applied to 9 samples (n=9) of each group. The maximum force was evaluated by flexion test with a perpendicular force applied to the long axle of the implant on a mechanical testing machine. From the generated graphics, the corresponding force (N) to the fracture of the implant was determined. The data analyzed statistically by one-way ANOVA and and Tukey's test (P< 0.05) showed that the Regular group (3.75mm) presented statistically significant higher fracture strength values than the Narrow group . The mean value for Narrow group was 261.5N, which is equivalent to approximately 70% of the resistance of the Regular group (378.1N). These data suggest that the use of narrow implants in possibly overloaded areas can increase considerably the risk of fracture, thus its clinical indication should be limited to upper lateral incisors and mandibular incisors when the placement of regular implants is not possible.171lima-thiaguinho@uol.com.br); OLIVEIRA, R.B.S.; JANSON, G.LIMA, T.F. ; PEREIRA, F.A.; SVERSUT, R.; PAULILLO, L.A.M.S.; SOARES, C.J.; SOARES, P.V.TOLENTINO, A.B. complaining about the presence of diastema and great gingival volume. The clinical examination showed that the patient had teeth with altered shape and size. In addition, it was observed that the insertion of the labial frenum was one of the reasons for the presence of diastema. For the implementation of treatment, it was defined the need for use of elastic spacers between teeth 21 and 22, followed by plastic periodontal surgery and correction of the insertion of the labial frenum. After 21 days of healing, impressions were taken for fabrication of a cast model and subsequent waxing and fabrication of a silicone matrix that would serve as a guide for the restoration. Composite resin shade was chosen using the VITAE scale and the restoration was carried out using the technique with layers of different shades in order to reproduce the dental structure. The finalization of the case was the polishing of restoration to obtain a smooth surface, avoiding the accumulation of plaque and facilitating cleaning. A simple, direct, minimally invasive and low-cost restorative technique provided a more harmonious smile with excellent esthetics and function. This allied to the periodontal plastic surgery brought satisfaction for the professional and patient.173dri_ubaldini@hotmail.com); PINI, N.I.P.; BENETTI, A.R.; PASCOTTO, R.C.; NUNES, M.C.P.; DANIELETTO, C.F.UBALDINI, A.L.M. complaining about the misalignment and severe staining of teeth 11 and 21. Clinical examination and radiographs confirmed the debility of the dental structures due to the presence of several restorations and endodontic treatment. The treatment consisted of cementation of posts and restoration with direct composite resin laminated veneers associated with opaque resin . The treatment reestablished the harmony of the smile while preserving functional integrity and periodontal health, other than providing psychological comfort to the patient. Therefore, this clinical report intends to present and discuss the indication, advantages, and disadvantages of direct composite resin laminated veneers.174vanessa_dreibi@hotmail.com); HIP\u00d3LITO, A.C.; CASAS-APAYCO, L.C.; MAGALH\u00c3ES, A.C.; HON\u00d3RIO, H.M.; WANG, L.DREIBI, V.M. . The specimens received the application of an etch-and-rinse bonding system (Adper Single Bond 2), previously modified by addition of rhodamine (0.16g/mL). Reconstruction was made with a nanotechnology composite resin (Filtek Z350). After 24 hours in water storage at 37\u00b0C, they were bisected longitudinally and polished. Laser confocal microscopy was used to analyze the hybrid layer characteristics. Different patterns of hybrid layer formation were observed, which can implicate clinical differences.175vanefs88@hotmail.com); GALLO, A.J.; GAETTI-JARDIM JR, E.SILVA, V.F. and Cytomegalovirus (CMV) are able to produce acute, persistent and chronic infections in different cell lines such as epithelial cells, lymphocytes and macrophages, leading to the development of suitable condition for microbial colonization of periodontal tissues. The present investigation evaluated the occurrence of these viruses in saliva, oral mucosa and biofilms from patients undergoing radiotherapy (RT) for treatment of head and neck cancer. Initially, these clinical samples were collected from 50 patients aged 16 to 80 years, while the achievement of clinical specimens. Sample collection was performed at baseline (prior radiotherapy), immediately after radiotherapy, 30, 90 d. after RT and 6 months after radiotherapy. Then total DNA was extracted by using Qlamp DNA Mini Kit and the presence of DNA of these two viruses was evaluated by nested PCR. The results showed the presence of EBV virus and CMV in 10% and 12%, respectively, before radiotherapy, while after radiotherapy, 88% of patients presented oral mucositis, and 44% harbored EBV in oral cavity and the same was detected in 54% for CMV. None of the patients who did not develop mucositis showed infection by CMV and EBV viruses at the time of collection of clinical specimens. The results of this study suggest that the cellular events and tissue involving radiotherapy for patients with head and neck cancer may be closely related to recurrence or reactivation of herpetic infections, which can affect the immune response of the patient and therefore the development of diseases associated with opportunistic pathogens.176vanessarmm@yahoo.com.br); ARCIERI, R.M. MARRA, E.M.O.; AZEVEDO, M.R.; LOUREIRO, R.M.T.; ONO, R.MACHADO, V.R. that competed and have been select for PROEXT 2006, program that contain programs and projects with emphasis on the social inclusion that strengthen the institutional act of extension in the ambit of the University Institutions. The purpose of this project is to give opportunity to the FUU dental students for extension activities in an integrated manner and with participation of different disciplines searching the social inclusion of 6-14-year-old students living in the rural zone by means of attention to their health and the implantation of public health policies permitting a behavioral and educational change of the future health professional. The UFU, by the Dentistry (5 professors and 47 students); Medicine (2 professors and 18 students) and Nursing (2 professors and 12 students) courses developed educational, preventive and curative actions directed at schoolchildren (6 to 14 years old). These project was developed on two ways: a) educational and preventive/ in the Rio das Pedras Settlement of Uberl\u00e2ndia/MG and Dom Bosco Rural Municipal School; b) Curative/ preventive assistance in the Medical/Dental outpatient service installed by the PACTo Project in the Rio das Pedras Settlement. Eight-seven families of the Settlement were assisted and 66 medical/dental consultations were provided to children aged 6 to 14 years. The actions at school included supervised oral hygiene, health education, chats, workshops, and enrolled 244 students, improving their health quality and rescuing their citizenship. The Project allowed that our students live the university extension, comprehending its challenge, the curricular amplification and the involvement between many disciplines through the relation and orientation at target population.177apaulav31@hotmail.com); OLIVEIRA, N.C.M.; BATISTA, J.D.; SARDINHA, M.C.; ZANETTABARBOSA, D.; SILVA, C.J.VIADANNA, A.P.O. . Besides, those injuries are usually associated to injuries in other parts of the body. The etiology of the facial fractures includes automobile accidents, physical assaults, falls, sporting and occupational accidents. The treatment and rehabilitation of this patient involves a detailed comprehension of evaluation, diagnosis and surgical technique. The facial fractures can be classified as mandibular fractures and fractures of the middle third of the face that includes maxilla, zygomatic and naso-orbito-ethmoid complex bones. We describe a case of a 20-year-old woman who has presented to Uberl\u00e2ndia Federal University with a history of bicycle accident. After a clinical and radiographic examination she was diagnosised with zygomatic fracture. During the clinical exam, the patient complained about paresthesia, diplopia and difficulty of ocular movement. The patient reported that she visited an eye specialist which associated the case to the imprisonment of the extrinsic eye musculature. Radiografic exams were requested and showed fractures of the floor left orbita. The patient was subjected to the reconstruction of the orbital floor with screw and titanium mesh screen. At 45 days postoperatively, the patient was well without complaints.178vipiccoli@hotmail.com); GARIB, D.G.; NAVARRO, R.L.; FRANCISCHONE, C.E.; OLTRAMARI-NAVARRO, P.V.P.; AYUB, P.PICCOLI, V.D. ; BARB\u00c9RIO, G.S.; SILVA, L.M.; LORENZONI, F.C.; MARTINS, L.M.; BONFANTE, G.MARQUES, V.R. by the adhesion of all reconstructive constituents and dental structure. Thus, tooth and restoration become a single structure and stress would be distributed more evenly to all constituents. However, obtaining this single body becomes more complex when a larger number of materials are incorporated. Besides the limitations of the adhesive luting agent inside root canal space, such as polymerization and moisture control, some incompatibility may occur between chemical or dual cured resin cements and simplified adhesive systems. This chemical incompatibility avoids the adequate polymerization of resin cements and these adhesive systems, naturally permeable to dentin fluids, promote an instable and weak adhesion. This work aimed at discussing the problems related to adhesive luting and their possible solutions, presenting a case report and a brief review of literature.180leandroataunesp@ig.com.br); BOSCO, A.F.; OKAMOTO, R.; MURAKAWA, A.C.; MORAES, R.O.; FERNANDES, L.A.SILVA, V.C. , on healing process of autogenous bone block grafts in young and aged rats, through the immunolocalization of the osteocalcin (OCN). Material and Methods: 96 female rats (Wistar) were used, being 48 rats with 3 months-old, divided in subgroups: Ovx, subjected the ovariectomy surgery and Sham, subjected to the same surgical procedure without the removal of the ovaries; and 48 female rats with 12 months-old, also divided in Ovx and Sham subgroups. After 30 days of Ovx or \u201csham\u201d operation, all the animals received autogenous bone block graft in the jaw, harvested from the calvaria. The animals were euthanized in 7, 14 and 28 days postoperatively. The specimens were subjected to histometric and immunohistochemistry analysis. This was accomplished in a semi-quantitative way, to analyze the immunolocalizations against osteocalcin, evaluating the interference of the estrogen in this process. Results: In Young group, there was smaller osteocalcin immunolocalization in the Ovx subgroup in all the experimental periods, compared with the Sham subgroup and the intensity increased with elapsing of periods. This also happened in the Aged group, however with less intense immunolocalizations when compared with the Young Group. Conclusion: Within the limits of this study, the estrogen depletion causes a decrease of bone mineralization in young and aged rats and those effects were more negative in aged group.181vivianeoaugusto@gmail.com); ARA\u00daJO, K.C.V.; AZEVEDO, R.M.C.; MESSI, A.C.A.; ONOFRE, M.A.; SPOSTO, M.R.AUGUSTO, V.O. are diseases that can be associated with emotional disturbances. The aim of this study is to present two cases emphasizing the importance of brief psychotherapy as auxiliary treatment of these lesions. Case 1: A 69-year-old woman presented to Oral Medicine Service (OMS) with a chief complaint \u201cpain in tongue and xerostomia\u201d. When clinically examined, we observed hypossalivation. The patient showed had emotional disorders, then was referred to psychotherapy service. In psychological interview, the patient reported family conflicts and thus existential crisis. It was applied two psychological tests. The Lipp's Symptoms of Stress Inventory for Adults resulted in \u201cStress in Exhaustion's Phase with Predominance of Physical Symptoms\u201d and the Beck's Depression, \u201cSevere depression\u201d. After several sessions of brief psychotherapy, the patient presented improvement of her emotional condiction and oral symptoms. Case 2: A 32 year-old woman, presented to the OMS complaining of \u201cburning mouth and injury inside the mouth\u201d. It was observed alteration suggestive of OLP. The patient also showed accented stress and anxiety, then was referred to the psychotherapy. In the interview she reported matrimonial conflicts with physical and moral aggression, affecting her emotional, causing oral symptoms. The Lipp's Symptoms of Stress Inventory for Adults resulted in \u201cStress in Exhaustion's Phase with Predominance of Physical Symptoms\u201d and the Beck's Depression, \u201cSevere depression\u201d. The psychological treatment, although still in initial phase, brought benefits contributing to the improvement of emotional and oral symptoms. Based on these findings, we believe that the brief psychotherapy as support on the treatment of some oral lesions presents satisfactory results in both dental and psychological way.182weglis.daiane@hotmail.com); KAYATT, F.E.; SANTOS, P.L.; SANTIAGO-JR, J.F.; GARCIA-JR, I.R.GOMES, W.D.S. , smaller surgical risk when compared to the grafts and, also smaller time of treatment.183williampereirar@hotmail.com); PEREIRA, J.R.; OLIVEIRA, J.A.; ZOGHEIB, L.V.; VALLE, A.L.; GHIZONI, J.S.ROCHA, W.P. in a universal testing machine at 45 degrees to the long-axis. Data were analyzed by one-way analysis of variance and Tukey test (\u00e1=.05). Significant differences (P<.001) were found among the mean fracture forces of the test groups . These results suggested that the amount of coronal dentin did not significantly increase the fracture resistance of endodontically treated teeth restored with prefabricated carbon fiber post and composite resin core.184ygor.fernandes@usp.br); FREITAS, A.R.; SALES-PERES, A.; SALES-PERES, S.H.C.FERNANDES, Y.R. (Ygor Renato Fernandes The human teeth banks (HTB) have great importance in the reuse of dental organs, since they contribute to the obtaining, sterilization, storage and donation to academics and researchers. The aim of this study was to highlight the methods of disinfection, sterilization and storage used in most HTB. There is controversy in the literature about the methodology used in the sterilization and storage of human teeth, as it presents so diverse and without defined protocol and some of these methods may cause structural changes in the dental elements in order to harm its use in scientific researches. The most used agents in laboratory studies for disinfection/sterilization of dental organs at the HTB include formalin, glutaraldehyde, sodium hypochlorite, autoclave, thymol, sodium azide and chloramine. Others studies was reported the freezing of dental elements, Cryopreservation and use of distilled water for storage of teeth. It may be concluded that there is need to establish a protocol to work in the HTB on standardization of methods for disinfection, sterilization and storage of dental organs, thereby ensuring that the management of these teeth be done in a safe way and without compromising the activities to which they are intended.185yuri_martinsc@yahoo.com.br); SILVA, R.S.; MELO, M.P.; MIRANDA, J.T.COSTA, Y.M. (Yuri Martins Costa The excessive range of motion of a joint is referred as hypermobility. Regarding temporomandibular joints (TMJs), it can be considered hypermobile those in which the condyle pass over the crest of the eminence during maximum mouth opening. The hypermobility can be a consequence of systematic disorders like generalized joint hypermobility, but can also be related with local factors like steeps eminences or loose ligaments. It is supposed that hypermobile TMJ may produce intracapsular instability by mechanical overload. This situation, combined with trauma, parafunctions or emotional stress can lead to the development of temporomandibular disorders (TMD). However, the relationship between hypermobility and TMD has not been well established. The aim of this study is to analyze through a literature review if hypermobility of TMJ can be considered a risk factor to the development of TMD. The used articles were selected from PubMed-Medline data base. Most of the clinical studies show that there is a relation between hypermobility and signs and symptoms of TMD. Despite the lack of standardized methodology research and general consensus, this review endorses a cause-effect relationship between hypermobility and TMD.186paulinne@netsite.com.br); MACHADO N.A.G.; GORRERI, M.C. FERNANDES-NETO, A.J.; NEVES, F.D.; MENDES, F.A.; BORGES, T.F.STRINI, P.J.S.A. (Paulinne Strini Temporomandibular disorders (TMD) are a set of signs and symptoms that affect the stomatognathic system and adjacent structures, generating mainly a pain able to radiate to inter-related structures. The purpose of this study was to evaluate the severity of TMD using the Helkimo Clinical Index (HCI) and Masticatory Performance (MP) in patients with TMD (n = 9) and compare it to the control group (CG) (n = 15), both with natural dentition and bilateral posterior occlusion. The MP tests were performed with the food simulator \u201cOptocal\u201d in portions of 17 cubes with 5.6 mm side and the subjects instructed to chew it for 20 (C1) and 40 (C2) masticatory strokes, monitored by a single examiner. The material collected was placed in a set of eight coupled granulometric sieves in a decresing order of opening. Then sieving, material collection, drying and weighing of the contents of each sieve were performed. It was calculated the geometric mean diameter of the chewed particle (MGD), obtaining a percentage of the MP index. The obtained data were subjected to the parametric Student Test t for independent samples (p <0.05). According to CHI, n = 8 patients presented severe TMD and 1 patient showed light TMD. The results indicated statistically significant differences (p = 0000) both for GC and for the TMD group . We conclude that patients with painful symptoms tend to have the chewing function impaired, requiring a treatment able to restore their physiological functions, improving their chewing ability and promoting their life quality.187dricunhacorreia@yahoo.com.br); CUNHA, R.F.; DELBEM, A.C.B.; NOVAIS, R.Z.CORREIA, A.S.C ; FERNANDES, Y.R.; SALES-PERES, A.; SALES-PERES, S.H.C.FREITAS, A.R. are viable alternatives to secure the acquisition of these items. Among the methods used for the decontamination of dental elements was observed the use of solutions such as formalin, thymol, sodium hypochlorite, glutaraldehyde and sterilization by autoclaving. It is concluded that the creation and standardization of HTB are of great importance to help researchers and academics in the safe acquisition of dental organs and also respecting the ethical and legal aspects to use these elements.189agda.ani@hotmail.com); BIANCO, K.G.; GAETTI-JARDIM JR, E.ANDREOTTI, A.M. (Agda Marobo Andreotti Aggregatibacter (Actinobacillus) actinomycetemcomitans, whose isolates were subjected to assess the potential of leucotoxigenicity using PCR. The presence and participation of periodontal pathogen microorganisms in the oral microbiota of mothers and children were assessed using conventional PCR and Real-Time PCR. Statistical analysis determined by means of multivariate logistic regression, the existence of correlations between the parameters studied, while, through the statistics and the Cochran Mantel-Haenszel and chi-square of Pearson were performed analysis of risk.The purpose of this study was assessed the presence of periodontal pathogen microorganisms in children aged 6 to 12 months, assisted by an educational-preventive program, its correlation with the oral microbiota and periodontal conditions of their mothers, and family socioeconomic and cultural aspects. After the evaluate socio-economic and cultural family through validated form, was held a clinical examination of mothers and children selected and their respective collections of saliva and subgingival biofilm. The saliva was collected at 6 months when edentulism, and after the initial eruption, were subgingival biofilm and saliva in 12-month period. The clinical specimens were transferred to tubes containing transport means and VMGA III cryotubes with Milli Q water. Specimens transported in VMGA III suffered dilutions and were inoculated on agar TSBV for the isolation of 190guto.aguilera@gmail.com); DUARTE, B.G.; GON\u00c7ALES, E.S.; CAPELOZZA, A.L.A.; DUARTE, M.A.H.AGUILERA, GS of lost teeth. It is necessary, therefore, appropriate amount of bone tissue and precise surgical planning need to install them. During the planning, measurement of bone availability appears to be fundamental and can be made using radiographs periapical, panoramic or in CT scan. The periapical radiograph is indicated in cases where we want to see details of the local bone anatomy, but does not allow precise measurements, since, even when performed with radiographic advices, magnification of the image cam occur. This fact seems not be consensus in the literature, since there are studies that suggest precise measurements with the periapical radiographic technique. The objective of this study was to verify the occurrence of magnification in images obtained by means of periapical radiographs, which are obtained from an dental implant placed in an artificial jawbone, with standardized time of exposure, processing and positioning. After obtaining the radiographic images of the implant, it was direct measured by millimeter ruler and the data were tabulated and analyzed statistically. The results showed magnification of the dental implant image.191aomelo2@hotmail.com); CARVALHO, C.A.P.; MARSICANO, J.A.; CARVALHO, F.S.; SALES-PERES, A.; SALES-PERES, S.H.C.MELO, A.O. . In the sample studied, the prevalence and severity of dental caries were considered low and behavioral factors were not considered significant to the development of disease. Further studies should be conducted to investigate the possible influence of these factors for the development of dental caries.192aldo_delcp@hotmail.com); BRAMANTE, C.M.; BERNARDELI, N.; MORAES, I.G.; GARCIA, R.B.; ZAPATA, R.O.DEL CARPIO, A . Twenty canals in 10 mesial roots of mandibular molars were cleaned and shaped using ProTaper and ProFile instruments to a size 35.04 taper at the apex and filled using RealSeal1 or Thermafil systems on mesial canal of each root. Horizontal sections were made at the 3 and 5 mm level from the apex and the percentage of sealer penetration in the root canal walls was analyzed using a CLSM. Thin layers of sealer (2-30\u03bcm) and sealer tags into dentinal tubules were found in the root canal walls in a high percentage using both techniques at both evaluated levels with no statistical differences between the techniques, T-student test (p>0.05). In conclusion, the percentage of sealer penetration in the root canal walls was similar using both thermoplastic carriers based systems.193alinecandido@hotmail.com); GON\u00c7ALVES, E.A.L.; SILVA, P.V.R.; CANDIDO, G.C.; COSTA, M.C.M.; COSTA, R.R.CANDIDO, A.G. ; GAETTI-JARDIM, E.C.; NETO, R.L.; TIMENETSKY, J.; OBIAGERI, N.F. FAPESP 08/53297-2.GERALDES, A.M. ; SAMPAIO-TEIXEIRA, A.C.M.; YAMASHITA, R.P.; FUKUSHIRO, A.P.; TRINDADE, I.E.K.IOST, A.V is an orthodontic procedure designed for the correction of maxillary atresia, which has the potential effect of changing nasal patency, usually impaired in individuals with cleft lip and palate. The purpose of this report is to present a clinical case of REM performed in a patient with cleft lip and palate and analyze its effect on the internal nasal dimensions in the short and long-term, by means of acoustic rhinometry. The technique allows the measurement of sectional areas of different nasal segments and thus the assessment of nasal geometry. In a patient with repaired unilateral cleft lip and palate, 15 years of age, male, minimum cross-sectional area of the nasal cavity (MCSA) was determined before expander installation and 2 months and 10 months after the active phase of expansion, using an Eccovision Acoustic Rhinometer (HOOD Laboratories). Measures were also taken after nasal decongestion in order to eliminate mucosal interference. For analysis, areas of the left and right cavities were added. MCSA corresponded to 0.70cm196claudieloliveira@gmail.com); ALMEIDA, L.R.B.; NAKAMUNE, A.C.M.S.; DORNELLES, R.C.M.OLIVEIRA, C.B. . With increasing age, the production and secretion of less E2 trigger loss of bone associated with menopause . The Raloxifene hydrochloride has selective agonist or antagonist activity on the tissues that respond to estrogen. The objective of this study was to analyze the process of alveolar repair and the plasmatic concentrations of phosphorus, calcium and estradiol in rats in different experimental situations. Thirty two Wistar rats, and 8 intact rats (2 m) with regular estrous cycle and 24 rats (18 m) ovariectomized (OVX) one year ago were used. During 60 days, the OVX rats received pellets containing estrogen (400 ug/17b-estradiol) or corn oil, these pellets exchanged every 30 days. Other group of OVX rats received raloxifene (1mg/Kg/d) by gavage. Under general anesthesia, the animals were subjected to extraction (28 days before euthanasia) of the upper right incisors for further analysis of the of alveolar repair process. At the end of the treatment period, animals were anesthetized for blood collection and the jaws were removed, decalcified and dried for the preparation of microscopic slides. The histometric analysis revealed bone formation of 51.12% (intact), 30.99% (OVX/oil), 50.28% (OVX/E2) and 36.93% (OVX / RLX) in the middle third of the animals studied. The plasma analysis showed significantly higher concentration of phosphorus in the group of OVX rats pre-treated with raloxifene and the concentration of calcium was lower in animals of group OVX/E2. In ovariectomized animals that received hormone replacement, the plasma concentration of E2 was significantly higher than that of the other groups. The 1-year results suggest potent activity of E2 and subtle of raloxifene on bone formation in OVX animals.197alyninha_reis@hotmail.com); ROSA, R.R.; BARBOSA DE PAULO, L.F.; SARGENTI-NETO, S.; CARDOSO, S.V.; LOYOLA, A.M.PAULA, A.R. . Most cases of PSCC are solitary lesions or part of a cluster of papillary lesions, some of which have evolved from preexisting papillomas and all of which have a fibrovascular core. These tumors are most commonly found in the oropharynx, hypopharynx, larynx, or sinonasal tract. This subtype of SCC is most commonly found in adults in their 70s and tends to affect men more frequently than women. The differential diagnosis should be made with other papillary neoplasms such as papilloma and VC. Surgery is the treatment of choice and adjunctive therapy may be used. The majority of PSCCs are at a low clinical stage (T1). Some authors report a better prognosis for papillary SCC than for conventional SCC when matched for T stage. We present a case of PSCC arisen in a 32-year-old woman that was referred to the oral diagnosis service with the chief complaint of an asymptomatic growing mass on the lateral border of the tongue. The mass had been there for nearly 1 month and no smoking or drinking vicious habit was reported. The medical history revealed diabetes type 2 and hypertension in treatment for cardiologist. The oral examination evidenced an exophytic mass, 2.5 cm in diameter, with a papillary aspect and white patches on the surface. A clinical diagnose hypothesis was papilloma and a incisional biopsy was performed. The histopathological analysis evidenced a PSCC. In view of this fact, the patient was referred to a head and neck surgeon for treatment.Papillary squamous cell carcinoma (PSCC) is a rare variant of squamous cell carcinoma (SSC) that can occur 198amandamessi@yahoo.com.br); AZEVEDO, R.M.C.; CHAVEZ, G.; AUGUSTO, V.O.; ANDRADE,C.R.; MASSUCATO, E.M.S.MESSI, A.C.A. is a potentially malignant epithelial lesion of the oral mucosa that attack the inferior lip. It is characterized by atrophic areas and lost of desing's lip. Can be associated with white plaques that cannot be scraped (leukoplakia), ulceration or crust. Prevalence is higher in white people and the main cause is exposure to the solar radiation without protection. The purpose of this work is to present a clinical case of a white man, 62 years old, carrier of diabetes and hypertension. The patient was smoker and worked in farming during 40 years. When clinically examined, painless inferior lip's atrophy associated with non-scraping white plaque could be observed. Our diagnostic hypothesis was actinic cheilitis with leukopakia and erosive areas. Before the incisional biopsy, a test with toluidine blue was performed, with retention in some areas. The histopathological examination revealed actinic cheilitis with moderate dysplasia. The pacient was referred to surgery to realize vermillectomy. And to the psychotherapy's service to receive emotional support and to be helpeld to stop smooking. We conclude that the early diagnosis is the main factor to the proginosis of potentially malignant epithelial lesion and that the psychologist's perfomance is important to the control of stress and complicantion's prevention.199amandinha_vk@hotmail.com); FAVAR\u00c3O, I.N.; SOARES, C.J.; URSI, W.; FONSECA, R.B.KASUYA, A.V.B ; SCORALICK, R.A.; MORAES, Z.M.; NARESSI, S.C.M.; DARUGE J\u00daNIOR, E.BARBIERI, A.A. ; IGREJA, B.B.; CARVALHO, A.A.F.; DORNELLES, R.C.M.ROSSI, A.C. mimics the beneficial effect of hormonal replacement compensating for the disadvantages of this therapy, being able to prevent bone resorption and reduce the risk of fractures. Studies point to the importance of the sodium fluoride in the composition and incorporation to present calcium in the bone, conferring to it higher resistance. The purpose of this work was to verify, through bone densitometry and analysis of plasmatic concentrations of calcium and phosphorus, if the association of fluoride and Raloxifen improve the bone quality of ovariectomized rats. Ten days after the ovariectomy, Wistar rats (6 m) received Raloxifen, through gavage, during 6 months. During this period, they received distilled water and distilled water + NaF/20 or 40 ppm. After 180 days, the animals had been anesthetized for blood collection and sacrificed by anesthetic overdose to remove femurs for evaluation of the maximum and minimum bone densities using Digora digital system in three regions from proximal epiphysis. The densitometry evaluation not evidenced alteration in the radiopacity/radiolucency in the three regions between the groups. The plasmatic results demonstrated that it does not have significant alteration in the calcium concentration between the groups. The plasmatic concentration of phosphorus was significantly lower in the animals of group RLX/20 ppm of NaF. The results suggest that the combination of anabolic and antiresorptive therapy changes in the metabolism of phosphorus, but did not alter the bone density of the femurs of experimental animals.202anacarolinaflorentino@gmail.com); AZEVEDO, M.R.FLORENTINO, A.C.A. ; CALABRIA, M.P.; FRANCISCONI, L.F.; PEREIRA, J.C.; RIOS, D.; WANG, L.HIP\u00d3LITO, A.C. ; OLIVEIRA, G.C.; PEGORARO, C.N.ROBERTO, A.F.B. ; BRAVO, D.M.C.; MONDELLI, R.F.L.; ISHIKIRIAMA, S.K.GARRIDO, A.M.R , and it is rounded value is 1.618. In dentistry, it is uses in lopsided initial evaluation and in planning esthetics treatments, obtaining as results both natural and artistic beauty. The aim of this work was to demonstrate how the golden proportion can be applied in dentistry to reestablish harmonics, functional and esthetic dimensions. The patient, a 45 year-old male, C.N.Q, came to the Bauru School of Dentistry unhappy with the appearance of his teeth. After clinical and radiographic examination defective restorations in the teeth 21 and 22 were diagnosed, presenting multiple diastemas and dental attrition causing alterations in anterior and canine guides. Plaster models were obtained and a diagnostic waxing was performed, based on the golden proportion theory, using a caliper, golden mean gauge and grids. The treatment plan included: oclusal adjustment, distalization of teeth 12 and 22 with a rubber band, gingival conditioning with composite increments, obtaining a silicone matrix to be used as a guide to facilitate the restorations technique, closure of the diastemas and increasing of the incisal borders of tooth 13 to 24 thus reestablishing the canine guide and the anterior guide. Finally, finishing and polishing were done. It was proven that golden proportion can be used to obtain esthetic improvements, reaching the expectations of both patient and dentist.206asmcorrea@yahoo.com.br); ALENCAR, E.N.; CUNHA, C.O.; PINTO, L.M.S.; CONTI, P.C.R.CORR\u00caA, A.S.M as an approach to oral health care that requires the judicious integration of systematic assessments of clinically relevant scientific evidence, relating to the patient's oral and medical conditions and history, with the dentist's clinical expertise and the patient's treatment needs and preferences. This concept requires that to be accepted as a study of great value to clinical practice a research needs to follow specific criteria and rigid methodology. Therefore, this literature review was based on studies with the highest level of scientific evidence as randomized controlled trials (RCTS) and systematic reviews including meta-analysis. A total of thirty-seven papers were held to assess the presence of evidence in manual therapy, pharmacotherapy, occlusal therapy, needling of trigger points, orthodontics, surgery and cognitive therapy used to control temporomandibular disorders (TMD). According to this review, evidence was found only for therapies as low level laser therapy and mid-laser, and for the analgesic effect of tricyclic antidepressants. The use of stabilization splints showed no efficacy in the treatment of TMD, but seems to be benefic in clinical practice. The occlusal adjustment is not supported by evidence and should be contraindicated. It is suggested that surgical therapy should only be indicated for refractory patients to reversible therapy. Cognitive therapy appears to be effective in the treatment of TMD. In general, more high-quality studies are needed to evaluate the effectiveness of these therapies in the treatment of TMD.207anaitadoretto@hotmail.com); SANTOS, M.J.P.; MENEZES, T.E.C.; AGUIAR, S.M.H.C.A.DORETTO, A. , presenting the methods used in dental care performed to these patients, their dental characteristics, needs and the reactions during the treatment. The records of 78 patients diagnosed with autism and assisted at CAOE were evaluated. These were selected through a survey carried out based on data, files of neurological diagnosis of the Center, using database (file DBF), considering the period from 1985 to 2004. From the 4 situations of dental care, it was observed that 24 patients went assisted through adaptation, 47 through physical restraint, 32 with sedation and 29 with general anesthesia. It was noticed the lack of oral hygiene raised upon the difficulty of dealing with autistic patients, classified as severe and aggressive, consequently presenting, in certain cases, high index of poor oral health and periodontal problems. In conclusion, this information is very important to health professionals, especially to those who work with Dental Care for Patients with Special Needs and, the physical restraint was the most used resource in assistance to these patients during their dental treatment.208andsofelipe@hotmail.com); PEREIRA, J.R.; ZOGHEIB, L.V.; OLIVEIRA, J.A.; VALLE, A.L.; GHIZONI, J.S.FELIPE, A.F. ; teeth with partially weakened roots (PWR) and teeth with and largely weakened roots (LWR). The control group was restored with glass fiber posts and a composite resin core. Teeth in the PWR and LWR groups were flared internally to standardized dimensions in order to simulate root weakness. Thereafter, the roots were partially filled with composite resin and restored in the same way as in the control group. The specimens were exposed to 250,000 cycles in a controlled chewing simulator. All intact specimens were subjected to a static load (N) in a universal testing machine at 45 degrees to the long axis of the tooth until failure. Data were analyzed by one-way ANOVA and Dunnett's test for multiple comparisons (p=0.05). There were statistically significant difference differences (p<0.01) among the groups , with significantly higher fracture strength for the control group. There was no statistically significant difference (p>0.05) between the weakened groups. The results of this study showed that thicker root dentin walls significantly increase the fracture resistance of endodontically treated teeth.209andre.carvalho.peres@usp.br); TAGLIAFERRO, E.P.; SALES-PERES, S.H.C.; AMBROSANO, G.M.; PEREIRA, A.C.; BASTOS, J.R.M.SALES-PERES, A.C. and 2006 (n=334). For data analysis, the DMFT, SiC Index and percentage of caries-free children were determined. The means (SD) for DMFT were 9.89(3.96) and 0.90(1.53), which the SiC Index were 14.34 to 2.63, in 1976 and 2006, respectively. The number of caries-free children (DMFT=0) ranged from 0.4% in 1976 to 63.8% in 2006. The fluoridation of water supply with other preventive methods available in Bauru city contributed to the occurrence of this great decline.210andre.scatolon@usp.br); CARDOSO, C.L.; CAPELOZZA, A.L.A.; FERREIRA J\u00daNIOR, O.; CONSOLARO, A.SCATOLON, A.L. ; ALMEIDA, M.R.; ALMEIDA, R.R.; OLTRAMARI-NAVARRO, P.V.P.; NAVARRO, R.L.; CONTI, A.C.C.F.KIMURA, A.Y. ; GREGHI, S.L.A.; REZENDE, M.L.R.; SANT'ANA, A.C.P.; FIGUEIRA, E.A.; RESENDE, D.R.B.SOUZA, A.P. ; CONTI, A.C.C.F.; ALMEIDA, M.R.; OLTRAMARI-NAVARRO, P.V.P.; ALMEIDA, R.R.; NAVARRO, R.L.ROSSETTI, A.P. ; BASTOS, R.S.; BASTOS, J.R.M.; SILVA, R.P.R.; CALDANA, M.L.; LAURIS, J.R.P.XAVIER, A. and DMFT (sd) were, respectively, 3.15 (3.12), 3.41 (2.69), 5.96 (4.19), 16.00 (7.30), 25.96 (9.82) and the percentages of caries free of 34.42, 14.81, 8.16 were credited for preschool children, schoolchildren and adolescents, respectively. The SiC index applied to the two younger groups were 6.65 and 6.70 increasing to 32.00 in 65 to 74 years old. At the teenager group the DMFT were 5.96 (4.19) and the Care Index still shows the low percentage of 29.40. In the elderly group, represented by 65 to 74 year olds, the data show the strongly neglected situation of oral health related with quality of life, it means almost the entire sample needed to use artificial dentures. Oral health in Monte Negro is synthesized by one word: \u201cnecessities\u201d. Oral health promotion and the prevention of oral disease policies are urgent needs.215angelicafardin@yahoo.com.br); SANGALLI, J.; GAETTI-JARDIM, E.C.; GAETTI-JARDIM JR, E.FARDIN, A.C. , hemin (5\u03bcg/ml) and menadione (1\u03bcg/ml) for the anaerobes and microaerophiles (A. actinomycetemcomitans), and Mueller-Hinton agar for E. faecalis. Antimicrobial activity of plants extracts on microbial biofilms was determined in microplates. Psidium cattleianum and Myracrodruon urundeuva extracts demonstrated significant inhibitory activity on all bacterial strains tested; alcoholic and aqueous extracts showed similar results. Psidium cattleianum and Myracrodruon urundeuva extracts were able to inhibit microbial biofilm while other extracts that produced inhibitory effects on planktonic cells did not show a significant inhibition of microbial biofilms. The aqueous extracts of P. cattleianum was the most effective on E. faecalis, producing a Log reduction of cellular viability of E. faecalis & C. albicans biofilm after 5 min. of direct contact, while the other extracts spent more than 2 h. to produce this effect.216acmjab@hotmail.com); CASTRO, A.L.; CRIVELINI, M.M.; GAETTI-JARDIM JR, E.MARQUETI, A.C. ; SILVA, V.F.; GAETTI-JARDIM JR, E.C.; GAETTI-JARDIM, E.C.GALLO, A.J. ; SILVA, C.J.; MARQUEZ, I.M.; FURTADO, L.M.; BATISTA, J.D.; ZANETTA-BARBOSA, D.BARBOSA DE PAULO, L.F. ; SPAGNOL, G.; SANTOS, P.S.S.; FREITAS, R.R.NAPOLES, B.B. . The objective of this work is a retrospective study of the clinical management of osteoradionecrosis. Were evaluated 6 patients who were subjected to surgery and conventional radiotherapy for malignant neoplasias of the head and neck. The selected patients had to present clinical and radiographic signs of osteoradionecrosis. Treatment of the lesions was established as curettage to stimulate bleeding, irrigation with 0.12% chlorhexidine and removal of bone sequestration. Of the 6 cases assessed, 3 (50%) had purulent drainage, from which microbiological culture was carried out and antibiotic therapy was administered for 14 days (combination of amoxicillin and metronidazole) with complete regression of signs of infection. Bone exposure persisted in only 1 (16.66%) of the patients, although it was asymptomatic. In 5 (83.3%) patients there was epithelialization of the area of bone exposure, which was also asymptomatic.220brubaguimaraes@yahoo.com.br); CARVALHO, M.L.; LIMA, D.C.; ARCIERI, R.M.MORAIS, B.G. of five cities of small port of the Northwest of the State of S\u00e3o Paulo, Brazil. The study was quanti-qualitative and the data had been gotten by interviews with the aid of a script half-structuralized for registers. It was verified that the members of the studied teams were young (of 18 to 29 years-old), with less of one year of work in the FHP and the majority lived in the city where they worked; the doctors and oral health team did not relate with other members of the team of the FHP, as well as the easiness of the nurses to relate with them. It was evidenced in the results, the difficulty of the professionals in becoming related in the Team of the FHP. There is a necessity to enable the teams to become, in fact, multiprofessional.221brumoron@usp.br); MAGALH\u00c3ES, A.C.; COMAR, L.P. WIEGAND, A.; BUCHALLA, W.; BUZALAF, M.A.R.MORON, B.M. were allocated by stratified randomization according to their surface hardness (SH) values into five groups: gel I \u2013 8% methylcellulose gel + 0.1 M lactic acid ; gel II \u2013 20 g/L polyacrylic acid + 0.1 M lactic acid, with 500 mg/L hydroxyapatite ; buffer I \u2013 50 mM lactic acid solution with calcium, phosphate and methyl diphosphonate ; buffer II \u2013 50 mM acetic acid solution with calcium, phosphate and fluoride ; cycl \u2013 pH-cycling. The final surface hardness (SH1) was performed to calculate the percentage of surface hardness change (%SHC). The samples were then longitudinally sectioned and sections (138\u00b17.6 \u03bcm) were subjected to transversal microradiography and cross-sectional hardness at 10 to 220 \u03bcm depth from the surface. There was a low linear relationship between mineral content and hardness . Generally, all groups presented similar hardness values except between some groups at specific depths. Regarding the mineral volume, buffer I produced higher demineralization than the other groups, followed by cycling, gel I, gel II and buffer II. The mean lesion depth was significantly different between gel I (35.79 \u03bcm) and buffer I (85.55 \u03bcm). Thus, the protocols for producing artificial caries lesion differ especially when considering the method of analysis.222bruninhamaggi@hotmail.com); BASSO, L.; CAMARINI, E.T.; FARAH, G.J.; IWAKI FILHO, L.; PAVAN, A.J.TEIXEIRA, B.M. ; ASSUMP\u00c7\u00c3O, T.S.; FIDELIS, N.S.; BERNARDINELI, N.; BRAMANTE, C.M.; GARCIA, R.B.CAVENAGO, B.C. . The filling materials were removed with: ProTaper Universal retreatment system; Mtwo R and hand instruments. Thermoelectric pair was kept in position in order to register the temperature on the cervical and apical thirds. Roots canals walls were analyzed at 12,5 magnification. The time, temperature and cleanliness rate were subjected to Tukey's test, and extrusion to Kruskal-Wallis and Dunn's test, (P<0.05). None of the techniques used was able to completely remove all the residues from the root canal. ProTaper showed the greatest extrusion of debris, shorter time and the highest temperature variation. The Mtwo R group was significantly less able to clean.224tamyluc@hotmai.com); RAHAL, S.; TESTA, R.; SANTOS, M.R.; BRISO, A.L.F.BUENO, T.L. ; SVIZERO, N.R.; D'ALPINO, P.H.P.; PALMA\u2013DIBB, R.G.; WANG, L.; ATTA, M.T.LIBARDI, C.C. ; FIAMENGUI FILHO, J.F.; DIAS, R.P.; AMADO, F.M.; ALMEIDA, A.L.P.F.; FIGUEIREDO, C.M.CIRINO, C.C.S. ; GHIZONI, J.S.; TAVEIRA, L.A.A.; SANT'ANA, A.C.P.; PEREIRA, J.R.ROSA, C.C. . Periodontal disease was more prevalent and severe in ischemic and hemorrhagic stroke than is systemically healthy patients, as observed by increased probing depth, attachment loss, bleeding on probing and plaque index . These findings suggest that periodontal disease can be considered as a risk factor for the development of stroke.228cazinha.daher@hotmail.com); PECCINATTI, C.B.; PISANI, M.X.; MALHEIROS-SEGUNDO, A.L.; PARANHOS, H.F.O.; SILVA-LOVATO, C.H.DAHER, C. were randomly distributed and immersed in coffee, coke and wine for 36 days (3 years). Next, the specimens were brushed with a bristle brush and water alone or associated with the dentifrices Corega Brite, Experimental 1 (Zonyl) and Experimental 2 (Chloramine T) in a brushing machine for 150 minutes (3 years), with the brushes and the dentifrice suspensions were replaced every 50 minutes. Six brushes were used being one for each specimen. The color was valued by spectrocolorimetry and the \u00c4E*ab was calculated after immersion in the solutions and after brushing regarding the initial color. The data were analyzed by ANOVA (P <0.05) and the color alteration was quantified by the National Bureau of Standards. After 36 days, there was statistically significant difference in DE*ab between three solutions, with coffee (12.28), coke (25.25), and wine (4.32) producing high, very high and acceptable color change. After the immersion in coffee, the difference of color lessened after brushing with water (18.48) and with chloramine (14.83), but remained very high. With the wine, the difference of color lessened after brushing with all products \u0394E*abT36=12.28; \u0394E*abT150=10.18. After the immersion in coke, there was no difference between products of hygiene, not even between the periods.229camilamaria_pr@hotmail.com); VALDIVIA, A.D.C.M.; ROSCOE, M.G.; NOVAIS, V.R.; CAMPOS, R.E.; SOARES, C.J.ROSATTO, C.M.P. post to provide optimal esthetic smile and a quality life for patient. Patient came to the Dental School of the University of Uberl\u00e2ndia in order to reestablish the esthetic of his maxillary anterior teeth, which had poor appearance, unsatisfactory endodontic treatments (teeth 11 and 21), extensive composite resin restorations and metalloplastic crown (12). First it was done internal bleaching of teeth 11 and 21 using sodium perborate mixed with 30% hydrogen peroxide. Then, FRC post was cemented in the same teeth (11 and 21); this post system present similar mechanical properties to dentin, resulting in similar stress patterns. After this procedure, teeth 13, 11, 21, 22 and 23 were prepared for indirect veneering and tooth 12 was prepared for total crown. The provisional restorations had been confectioned from a diagnostic waxing, using the silicone matrix shell and composite resin. Impressions were made using a condensation silicone material and retractor wire. The definitive restorations were fabricated in feldspathic ceramic because this material warrants esthetic success, in addition to having biomechanical characteristics close to that of the enamel. The restorations were cemented with adhesive luting cement. Esthetic and functional adjustment of the restorations was done. Complete functional and esthetic rehabilitation was achieved because of the biomechanical characteristics of all used materials, confirming this as a good alternative of rehabilitation.230mila_mmoraes@hotmail.com); RAMIRES, I.; GRIZZO, L.; OLIVEIRA, R.C.; MAGALH\u00c3ES, A.C.; BUZALAF, M.A.R.MORAES, C.M. coupled to a potentiometer. Following analysis, the samples were classified as acceptable or unacceptable according to their fluoride concentration. Descriptive statistical analysis was utilized. The mean fluoride concentration observed in the different collection months ranged from 0.10 to 2.63 mg/L. Around 86.6% of the samples were classified as acceptable and among them, 36% were regarded as optimum. Additionally, 12.2% of the samples were considered inadequate (more than 0.84 mg fluoride/L). The results indicate a tendency from optimum fluoridation to overfluoridation. When the present data are compared to previous data reported for the city, it can be seen that the conditions of public water fluoridation have been improved after the implementation of the external monitoring. Thus, the implementation of the monitoring of water supply fluoridation by means of surveillance systems must be stimulated, since this is fundamental for controlling dental caries.231gracicristina@hotmail.com); COSTA, F.; FARAH, G.J.; IWAKI FILHO, L.; TRINDADE, J.P.; CANDIDO, A.G.; SILVA, P.V.R.CANDIDO, G.C. ; SHINOHARA, A.L.; SILVEIRA, E.M.V.; LAURIS, J.R.P.; ANDREO, J.C.; RODRIGUES, A.C.MELO, C.G.S. which allows the passage of emissary veins, communicating the cavernous sinus to the pterygoid venous plexus. This fact highlights its importance because clinically it can transmit serious infections to the middle cranial fossa. The FV is located in the greater wing of sphenoid bone between the foramen ovale (FO) and the foramen rotundum (FR), and anteriorly and medially to the FO. The FO allows the passage of the mandibular branch of trigeminal nerve, which is the target of the trigeminal radiofrequency rhizotomy (TR). The TR is a surgical technique used in the treatment of the trigeminal neuralgia (TN). This technique promotes a great pain relief in the immediate postoperative. In this procedure a puncture of the medial margin of the FO is performed to reach the trigeminal ganglion. During this procedure many attempts are made before the right puncture, and the FV can be accidentally reached. A needle insertion through the FV can cause serious complications. Actually in the TR, the professional is guided by high-tech equipment, but the knowledge of the relevant anatomy makes this technique safer and precise. Therefore, this study intend to offer specific anatomical data with morphological patterns (macroscopic and mesoscopic), to increase the understanding of the FV features as frequency, incidence and important distances with adjacent foramina. This information can help the surgeon to improve the planning, and to have a safer execution of the TR by the fact of avoiding the accidental puncture of the FV.233carla_cmendes@hotmail.com); ARANTES, F.M.; GON\u00c7ALVES, M.J.B.; KINA, J.; GURGEL, J.A.; SANTOS, E.C.A.MENDES, C.C. of 9 subjects each. Mini implants were placed in group A and lingual button were placed in group B. Two study casts were obtained for each patient, one at the beginning of the treatment (M1) and the other at the end of canine retraction (M2). The measurement of study casts were performed using the Autodesk Autocad 2007 program. All measurements were tabulated and subjected to analysis by paired \u201ct\u201d test to verify the intra-examiner method of error. To determine the casual error, was used the formula proposed by Dahlberg . To compare the initial and the final phase was used the paired \u201ct\u201d test. Student's \u201ct\u201d test was applied to compare between the mini implant and lingual button groups. A significance level of 5% was used for all of tests. The statistical analysis was performed in the Statistica for Windows version 5.1 software . There was no statistically significant difference between the two groups comparing in the study casts the loss of anchorage of molars after the initial retraction of the upper canines using two different systems of anchorage .234carlla.martins@gmail.com); PEREIRA, F.A.; REIS, B.R.; SILVA, G.R.; SOARES, C.J.; SOARES, P.V.GUIMAR\u00c3ES, C.M. ; VIEIRA, D.M.; REIS, E.S.; ROSSETTI, P.H.O.; PADOVAN, L.E.M.; FRANCISCHONE, C.E.BARROS, C.A.V.S. slices generated on a computerized three-dimensional virtual environment. Five completely edentulous patients were enrolled in this pilot study. After reverse planning for tooth set-up and tomographic guide fabrication, CTs were made 0.2mm thick with images generated on Dental Slice (Bioparts) for placement of Titamax EX cone-morse implants . After implant placement, new CTs were made following the same protocol and transferred to Dental Slice software. Mean angular deviation values were of2.033 \u00b1 0.782\u00b0; registered linear differences at implant platform, middle and apical thirds were 1.082 \u00b1 0.907mm, 1.599 \u00b1 1.22mm, and 2.542 \u00b1 2.047mm, respectively. All acrylic-veneered, metal-reinforced definitive prostheses were installed after 48 hours and occlusal adjustments provided after 72 hours. No clinical complications were seen, with all implants and prostheses remaining into function. Within the limits of this study, the results showed that this technique is safe and accurate for routinely dental practice. However, these values must be confirmed in further studies.236carolff@usp.br); FRANCISCONI, L.F.; SCAFFA, P.M.C.; SILVA, R.V.C.; CASAS-APAYCO, L.C.; FRANCISCONI, P.A.S.FRANCISCONI, C.F. ; MESSORA, M.R.; NAGATA, M.J.H.; BOSCO, A.F.; FURLANETO, F.A.C.; GUSKUMA, M.H.SANTINONI, C.S. is based on the premise that platelets constitute a reservoir of critical growth factors, which once released, may positively regulate the wound healing process. Currently, studies have been reported on the regenerative capacity of PRP, which has been successfully combined with bone grafts in oral reconstructions and in Implantology. The purpose of this study was to report on a case with a horizontal alveolar ridge deficiency (Class I by Seibert 1983) in the anterior area of the maxilla, treated by PRP combined with autogenous bone block graft. After 6 months, the thickness of the alveolar ridge was enhanced and the placement of an osseointegrated implant in the area was possible. The use of PRP combined with bone graft can be successfully used in the reconstruction of alveolar ridge deficiencies.238carol_lodi@yahoo.com.br); AMARAL, J.G.; DELBEM, A.C.B.; SASSAKI, K.T.; MARTINHON, C.C.R.LODI, C.S. , calcium (Ca), phosphate (P) and alkali-soluble carbohydrates on the biofilm were analyzed. The analysis of F was accomplished with ion specific electrode and the Ca, P and carbohydrates with the spectrophotometer. The initial and final microhardness were determined for evaluation of the mineral loss. The data were subjected to the Kruskal Wallis and Miller tests (p<0.05). The results showed that the 1100 \u03bcg F/g dentifrice presented the highest concentration of F, Ca, and P ions in the biofilm followed by 500 \u03bcg F/g dentifrice and placebo. Carbohydrate concentration and the percentage of mineral loss were the highest in the placebo and the lowest in the fluoride dentifrices. According to the results, it was observed that 7-day experimental period and 30% sucrose solution were sufficient to the cariogenic biofilm formation with demineralization of the enamel when exposed to the challenge 6 times/day, even with the use of fluoride dentifrice.239carolknob@usp.br); LANCIA, M.; SATHLER, R.; FERNANDES, T.M.F.; HENRIQUES, J.F.C.KNOB, C.D. ; GENNARI FILHO, H.ZAZE, C.A. ; DAHER, C.; PISANI, M.X.; PARANHOS, H.F.O.; SOUZA, R.F.; SILVALOVATO, C.H. FAPESP IC n\u00b0 08/52133-6PECCINATTI, C.B. of a relining material were made and randomly divided into three groups (n = 18): negative control , positive Control (1% hypochlorite) and experimental (Ricinus communis). The immersion in beverages was simulated for 36 days, representing 3 years. After that, the specimens were immersed in cleansers for 15 days, simulating 20-minute daily immersions for 3 years. The color and surface roughness were assessed after finishing, after staining and after immersion in cleansers. Data from each group of beverages were analyzed independently with the Kruskal-Wallis test (P < 0.05). The color analysis obtained after immersion in coffee and Coke and after immersion in the cleansers indicated that the hypochlorite caused a significant color alteration and Ricinus communis was statistically similar to water. After immersion in wine, there was a difference between the solutions and hypochlorite caused the highest color change, followed by Ricinus communis and water. Regarding the surface roughness, there was no statistically significant alteration in the groups of coffee and Coke. After immersion in wine, there was an increase in roughness compared to the baseline values, hypochlorite caused a reduction in this property, while the other cleansers did not cause roughness alteration. All tested cleansers produced significant color alterations. Sodium hypochlorite was the main responsible for color alteration and roughness reduction in the wine group.242christinemen@hotmail.com); SCHUTZ, C.Y.K.; SELL, A.M.; GARCIA, J.N.B.; CASAROTTO, A.R.; HIDALGO, M.M.MARTINS, C.M. and distilled water (negative). The study evaluated freshly opened Euro-Collins\u00ae and the solution open for 30 and 120 days and kept at room temperature of 25\u00b0C. The cells were isolated from peripheral blood of healthy donors (n = 4), stored in the test media and samples were collected at 0, 1 h, 3 h, 6 h and 24 h to be analyzed by the Trypan blue dye exclusion method for assessing cell viability.. The results were subjected to ANOVA and Contrast statistical tests. Analyzed over the time, Euro-Collins\u00ae opened 120 days had worse performance (p <0.05) from the first hour than milk and HBSS, and better than distilled water. The Euro-Collins\u00ae opened 30 days and freshly open differed from the control HBSS (p <0.05) at 3 and 6h, respectively. Also it was measured the pH of all solutions and only distilled water showed pH incompatible with cell proliferation. The results suggest that under the tested experimental conditions, the Euro-Collins\u00ae may be indicated for the maintenance of cell viability for less than 3h, using freshly opened solutions or opened for a maximum period of 30 days. Studies should be performed with other cell types.243cibelegomes@lpnet.com.br); DUARTE, M.A.H.; BONELLI, A.C.C.; GAMBARINI, C.T.A.G.; MORAES, I.G.; VIVAN, R.R.GOMES, C.C. . The tests were carried out in accordance with ADA's #57 specification with the addition of the needle of 456,6 g for the setting time, in accordance with the ASTM's #C266-03 specification. In relation to the setting time, the results showed that MTA Angelus presented the shortest initial setting time together with MTA Bio, followed by Portland cement clinker associated with bismuth oxide and calcium sulfate. The logest initial setting time was of Sealepox RP. Portland cement clinker associated with bismuth oxide and calcium sulfate was the material that presented the longest final setting time, followed by Sealepox RP and MTA Angelus and Bio (thre two one with the same times). Regarding the solubility, the lowest values were found for light-curing MTA, followed by Sealepox RP. MTA Angelus and MTA Bio presented the highest values, followed by Portland cement clinker associated with bismuth oxide and calcium sulfate. It may be concluded that the setting time vary a lot among the evaluated materials. Regarding the solubility, light-curing MTA and Sealepox RP presented values within the limits established I the ISO 6876 (2001) standard.244franisaak@uol.com.br);VIEIRA, E.M.M.; \u00c1VILA-CAMPOS, M.J.; GAETTI-JARDIM JR, E.CIESIELSKI, F.I.N. ; BRAMANTE, C.V.; BRAMANTE, A.S.; GARCIA, R.B.; MORAES, I.G.; BERNARDINELI, N.RODRIGUES, C.T. ; ALMEIDA, L.R.B.; NAKAMUNE, A.C.M.S.; DORNELLES, R.C.M.OLIVEIRA, C.B. . With increasing age, the production and secretion of less E2 trigger loss of bone associated with menopause . The Raloxifene hydrochloride has selective agonist or antagonist activity on the tissues that respond to estrogen. The objective of this study was to analyze the process of alveolar repair and the plasmatic concentrations of phosphorus, calcium and estradiol in rats in different experimental situations. Were used 32 Wistar rats, and 8 intact rats (2 m) with regular estrous cycle and 24 rats (18 m) ovariectomized (OVX) one year ago. During 60 days, the OVX rats received pellets containing estrogen (400 ug/17b-estradiol) or corn oil, these pellets exchanged every 30 days. Other group of OVX rats received raloxifene (1mg/Kg/d) by gavage. Under general anesthesia, the animals were subjected to extraction (28 days before euthanasia) of the upper right incisors for further analysis of the of alveolar repair process. At the end of the treatment period, animals were anesthetized for blood collection and the jaws were removed, decalcified and dried for the preparation of microscopic slides. The histometric analysis revealed bone formation of 51.12% (intact), 30.99% (OVX/oil), 50.28% (OVX/E2) and 36.93% (OVX / RLX) in the middle third of the animals studied. The plasma analysis showed significantly higher concentration of phosphorus in the group of OVX rats pre-treated with raloxifene and the concentration of calcium was lower in animals of group OVX/E2. In ovariectomized animals that received hormone replacement, the plasma concentration of E2 was significantly higher than that of the other groups. The 1-year results suggest potent activity of E2 and subtle of raloxifene on bone formation in OVX animals.247RIBEIRO, C.P. (Cl\u00edcia Pereira Ribeiro cliciaribeiro@foa.unesp.br); HILDEBRAND, M.C.; CIESIELSKI, F.I.N.; VIEIRA, E.M.M.; GAETTI-JARDIM JR, E.FAPESP 2007/51016-3H. pylori infection and transmission, but conflicting evidence exists about the occurrence of this microorganism in pre-Colombian societies that maintain strong relationship with the ancestors' traditions. Thus, the aim of this study was to determine the occurrence of H. pylori in the subgingival biofilm of 100 native Brazilians from Umutina Indian Reservation, Mato Grosso State, with different conditions of periodontal health, in comparison to a group of non-Indians presenting similar periodontal and socioeconomic status. Relevant dental and periodontal parameters and general health parameters, were recorded. Samples of subgingival biofilm were collected and the presence of H. pylori DNA was evaluated through nested PCR. The second PCR was performed using 5 \u00ecL of the first PCR reaction. Primers for both rounds of PCR were designed to amplify H. pylori-specific segments within the bacterial 16S rDNA. The primers used in first-round PCR were EHC-U and EHC-L, while in the second round of amplification, primers ET-5U and ET-5L were used, producing a 230-bp fragment within the amplicon of the first-round PCR. In Indians, this bacterium was detected in subgingival biofilm from 21.43% healthy subjects, 33.33% gingivitis patients and 34.21% periodontitis patients. In periodontal specimens from non-Indians, the presence of H. pylori was observed from 32.65% healthy subjects, 26.67% gingivitis patients and 38.46% periodontitis patients. This confirms the role of oral cavity as a reservoir of the microorganism and it was not found any significant difference between the occurrences of this rod from Indians and non-Indians, despite of deep differences observed in the diet and personal habits of these communities, and this microorganism did not evidence any association with periodontal status of the patients.The periodontium has been suspected as an extra-gastroduodenal reservoir for 248coelhobmf@hotmail.com); MOTTA-J\u00daNIOR, J.; FERNANDES, S.K.; MATHEUS, A.R.; STABILE, V.A.G.; PINTO, R.J.COELHO, D. ; MAIA, L.P.; SILVA, E.R.; TABA J\u00daNIOR, M.; GRISI, M.F.M.; REINO, D.M.INGRACI - DE LUCIA, C. ; KAMEI, N.C.COSTA, R.R. and intrinsic factors (systemic state). The lesion is often found in adult Caucasian males. The occurrence of metastasis is due the delay in the diagnosis of the lesion. The treatment is surgical and the risk of recurrence depends on the tumor's stage. This study intended to demonstrate the multidisciplinary performance of the oral and maxillofacial surgeon with head and neck surgeon by the presentation of a case of epidermoid carcinoma in the retromolar region that needed cervical emptying. The lesion of interest in both areas leads to the formulation of a multidisciplinary team still poorly reported. However, this type of performance provides an effective and qualified attendance giving satisfactory outcomes.251dabi_musa@hotmail.com); ALEIXO, R.Q.; RODRIGUES, M.T.V.; COSTA, M.R.S.N.; GALV\u00c3O, N.S.; ALMEIDA, D.L.NASCIMENTO, D.O.R. (Dabiliane Oliveira Rodrigues Nascimento Paracoccidioidomycosis (PCM) is a systemic and endemic fungal infection caused by Paracoccidioides brasilienses, dimorphic and native from South America, found in soil, plant and water of rural areas. The human contamination occurs by inhalation and primary infection is pulmonary. It is reported chronic, acute/subacute and sequelae or residual clinical forms. The purpose of this study is report a case of oral lesions of PCM and the dentist's role in signs and symptoms identifications. A 49-year-old black male, smoker, farmer, complained of \u201cpain in the lips and cheek, the inside\u201d, 4 months ago. After intraoral examination, it was observed ulcerative \u201cmulberry-like\u201d lesions in the inferior and superior buccal sulcus, cheeks bilaterally, attached gingiva, alveolar ridge and oral floor, lower macroqueilia and regional limphadenopathy, typical secundary features of PCM. Incisional biopsy was performed in lower lip and attached gingival. Histopathological analysis confirmed clinical presumptive diagnosis: PCM. Patient was referred to the center of reference in systemic mycosis (CEMETRON) for systemic therapy. PCM patients are usually male, adults, farmers, smokers and expressing chronic PCM. They may complain of sleepness, weakness, inappetence, dysphagia, dyspnea, cough, hemoptysis, fever, weight loss, pruritus and burning. On extraoral examination there is macroqueilia, pallor, swelling and cervical lymphadenopathy. There may be relapse in wound healing after tooth extractions. In the mouth, the places most affected are lips, cheeks, floor, tongue and pharynx. The periodontum can be compromised, resulting in tooth mobility. Microscopically, the lesions show multibudding yeast issue with \u201cMickey Mouse\u201d aspect. The findings observed in this patient coincided with the literature, emphasizing the dentist importance in using routinely diagnostic methods, biopsy when necessary for correct analysis of diseases that affect the patient systemically, and for the differential diagnosis: squamous cell carcinoma, hystoplasmosis, tuberculosis, coccidioidomycosis, syphilis, Weneger's granulomatosis, sarcoidosis and leishmaniasis.252danielodonto63@hotmail.com); DUARTE, D.M.; FURTADO, L.M.; BARBOSA, D.Z.; MARQUEZ, I.M.RESENDE, D.A. ; CUNHA, R.F.OLIVEIRA, D.C. with fluoride varnish (FV) in the prevention of dental caries on permanent first molars. The trial targeted eighty children aged 6 to 8 years, with all four newly erupted permanent first molars present. Two permanent first molars on one side of the mouth were sealed with Fuji Triage, a glass ionomer sealant; fluoride varnish (DURAFLUOR) was applied on the other two permanent first molars. Evaluation of sealant retention was performed after 6 months, using Simonsen's criteria. The effectiveness of both materials in the prevention of dental caries was also evaluated. Out of the 160 sealed teeth, 13 (8%) presented full sealant retention, 127 (79%) presented partial sealant retention, and the sealant was missing in 20 teeth (13%). Regarding the preventive effect on the sample of 320 teeth, only 12 (4%) treated teeth became carious. Of those, six were sealed with GIS and six treated with FV. It was concluded that complete retention of the GIS was very low; however, no difference in caries increment between both treatments was found.254danielapupulim@hotmail.com); PIERI, L.V.; HENRIQUES, J.F.C.; JANSON, G.; FREITAS, M.R.; PINZAN, A.PUPULIM, D.C. (Daniela Cubas Pupulim The interlandi headgear (IHG) is indicated mainly in the mixed dentition for upper molar distalization in the Angle Class II Division 1 malocclusion. A 9-year old girl with severe convex profile and severe horizontal trespass, without any space for the eruption of the permanent upper lateral incisors, was treated with a IHG appliance 24 hours/day with 350g each side for seven months. In the lower arch, a Schwarz appliance was applied in order to uprigth the lower teeth. Then, the upper and lower fixed appliances were placed to align and level the teeth. The IHG was efficient in moving upper molars distally with a body movement once the forces passed through the center of resistance bringing about sufficient space for eruption of the permanent teeth and a harmonic facial profile.255carol_danieletto@hotmail.com); COSTA, F.S.; CAMARINI, E.T.; IWAKI FILHO, L.; PAVAN, A.J.; FARAH, G.J.DANIELETTO, C.F. ; PEREIRA, T.S.; SILVA, J.Z.; CUNHA, R.F.; NERY, R.S.; AGUIAR, S.M.H.C.A.CAMARA, D.M. had a record of oral alterations. The 0-12-month-old age group (53.2%) and females (50.6%) presented most oral alterations. Primary herpetic gingivostomatitis was the most prevalent oral alteration (25.3%). In 53.2% of the records, some kind of treatment for the diagnosed oral alteration was necessary. Thus, based on the methodology used and the obtained results, it may be concluded that oral alterations are not associated with gender and a treatment is needed in most cases. Moreover, the early dental care to the baby becomes increasingly close to reality and allows the diagnosis of several types of oral amendments, as well the clarification to parents and/or guardians about proper behavior.257deborapelegrino@yahoo.com.br); ALVARENGA, A.C.F.; ROSCOE, M.G.; SOARES, P.V.; SANTOS-FILHO, P.C.F.; SOARES, C.J.FERREIRA, D.P. ; between 6 and 12 years ; between 13 and 19 years (19.3%); between 20 and 30 years (17.3%) and above 30 years (15.3%). The relation of the factors in study according to the ages was: between 6 and 12 years, the occurrence of dentoalveolar trauma was higher in men (48%), tooth #11 (44.3%) being the most often affected and crown fracture (56.1%) most frequent type of trauma. In general, the most frequent trauma was crown fracture (59.4%), which occurred predominantly in patients aged 6 to 12 years (56.1%). The teeth most involved, had been uppers central incisors (71.8%) for the position most vulnerable in the dental arch. Based on the knowledge of the type of trauma versus the patient profile, preventive programs must be developed, emphasizing the importance of the use of mouthguards for children in daily activities and mainly when engaged in sports or risky activities.258dennisouza@gmail.com); MORANDO, F.S.; NOSE, A.R.SOUZA, D.D. . For correction of this deficiency, patients who have mature bone may undergo surgically assisted rapid maxillary expansion, whose principles have been proven a great choice for the treatment of this deformity. In other cases, such as discrepancies greater than 4 mm, failure of previous orthodontic treatment and transverse discrepancy greater than 7mm, this technique also can be used. The present study has the objective to show all of the steps of a surgically assisted rapid maxillary expansion by reporting of the case of a 28-year-old female patient under general anesthesia, treated at Southern Regional Hospital, S\u00e3o Paulo, Brazil.259rodio87@hotmail.com); ALMEIDA, M.R.; ALMEIDA, R.R.; OLTRAMARI-NAVARRO, P.V.P.; NAVARRO, R.L.; CONTI, A.C.C.F.RODIO, D.C. or can appear associated to a Class I. Etiologically, it is provided by a trauma, lost or retention of the deciduous teeth, inadequate perimeter of the dental arch, interposition of the upper lip, ectopic eruption of permanent teeth. There is also the possibility to occur associated with the functional protrusive mandibular shift or because of a maxillary hypodevelopment. A differential diagnosis for the situations mentioned above is very important to make sure if there is a bone involvement (Class III) or only a dental involvement (Class I). The prevalence of the anterior crossbite reaches 7.6% among the malocclusions. The therapy depends on a differential diagnosis and is based on the correction of the buccolingual relationship of the anterior teeth, providing a normal growth and developing of the jaws. Among many treatment options, this work aims to emphasize the importance of the interceptive treatment in two clinical cases. On the first case, the anterior crossbite has as an etiologic factor the long retention of the deciduous central incisor, causing a deviation of the permanent right central incisor eruption. On the second case, the anterior crossbite was originated from a trauma on the deciduous incisors with displacement to the lingual region of the permanent incisor. This ectopic eruption can be associated with an occlusal trauma with the lower incisors causing a gingival recession. The treatment protocol was based on the use of a removable orthodontic appliance with double loops for the first case and a removable orthodontic appliance with expansive screws and a simple loop for the second case.260almeida.dino@hotmail.com); GALV\u00c3O, N.S.; NASCIMENTO, D.O.R.; MENEZES, K.E.; BATISTA, K.M.; DIAS, A.G.A.ALMEIDA, D.L. were used to obtain data, DMTF to indicate the rates of caries, and the Community Periodontal Index (CPI) for periodontal disease. The examination was performed by 2 examiners and 2 registers, who were calibrated in advance according to Kappa index . The participants in this study were 102 children of both genders. The results showed that 37.25% of the schoolchildren were caries-free (n=38). As for the mean DMTF, a result of 1.29 (\u00b11.55) was obtained. The CPI of the examined adolescents showed that 48.2% of the teeth did not present gingival bleeding, 33.2% had bleeding, 17.3% had calculus, 0.2% sextants were excluded and 1.1 sextants were not examined. At the end of the stidy, it was observed that the schoolchildren presented a high prevalence of gingivitis compared to caries disease. Such results allow us to conclude that the need to implement educational measures of oral hygiene orientation, directed to the adolescent public of the schools.261diurianne@terra.com.br); MONTI, L.M.; CASTRO, A.L.; SOUBHIA, A.M.P.; AGUIAR, S.M.H.C.A.FRAN\u00c7A, D.C.C. ; TJIOE, K.C.; GON\u00c7ALES, E.S.; SANT'ANA, E.; FERREIRA J\u00daNIOR, O.; OLIVEIRA, D.T.DUARTE, B.G. (Bruno Gomes Duarte Adenomatoid odontogenic tumor (AOT) is a rare odontogenic lesion that accounts for 3 to 7% of all odontogenic tumors. It presents as a slow growing symptom-free lesion and shows predilection for the anterior region of the maxilla and young females. Radiographically, AOT presents as a radiolucent lesion, with regular margins, associated with an enclosed tooth \u2013 most commonly canine. On the histological exam of a classic AOT lesion, it is possible to see numerous spindle-shaped cells forming rosette as well a the characteristic duct. Calcified areas are present in most AOT. The diagnoses has being based in the clinically, radiographic and histopathological reports. Surgical enucleation is the treatment of choice, because AOT have a benign behavior with rare recurrence. The aim of this study is presents a case of adenomatoid odontogenic tumor with 4 years of follow-up. The patient, W.H, male, 12 years old, presented with main complain of delay in the exfoliation tooth 53. In the intraoral examination revealed painless swelling in the right region of maxillary. A rigid mass and mucosa integrity was observed. Radiographic examination revealed an extensive radiolucent area, with well-defined margins. Tooth 13 was involved by the lesion and was displaced by the mass. The first diagnostic was dentigerous cyst. After incisional biopsy and microscopic analysis we could detect a virtual cavity coated by a delicate cuboidal epithelium. It could be observed proliferation of odontogenic epithelial cells and duct-like formation. As the final diagnosis of AOT, the lesion was removed by enucleation together with the tooth, and the patient was followed after 8, 14, 60 and 180 days, and after 4 years, not showing clinical or radiographic signs of tumor recurrence.263eduardo_muncinelli@hotmail.com); BERNAL, M.A.C.; MATARAZZO, F.; FAVERI, M.; FERES, M.; FIGUEIREDO, L.C.MUNCINELLI, E.A.G. in smoking and non-smoking individuals with chronic periodontitis. Clinical and microbiological evaluations were performed. Subgingival samples were analyzed by Checkerboard DNA-DNA hybridization. SRP did not exceed 21 days. The clinical examination was performed in the beginning, 90 and 180 days post-therapy, and microbiological in the beginning, immediately after SRP, 42, 90 and 180 days. The SRP promoted clinical significant improvements in all the parameters in the group NS (p<0.05), however, for the S group differences were not observed in the gingival bleeding and bleeding on probing . The greatest microbiological benefits was noticed in NS group, where P. gingivalis was maintained in inferior levels (p<0.05) up to 180 days; and the beneficial species increased from 20.1% for 50.8% (p<0.05), and the pathogenic increased from 72.6% to 27.3% (p<0.05). The S group beneficial species passed from 24.1% to 35.3% (p<0.05), however the pathogenic species passed of 69% for 55.3% (p>0.05) to 180 days. In conclusion, the therapy of SRP promoted clinical improvements in the smokers and non-smokers. However, the recolonization of the subgingival environment by pathogenic microorganisms was more obvious in the smokers.264CONSOLMAGNO, E.C.; OROSCO, F.A; BRAMANTE, C.M.; BERNARDINELI, N.; GARCIA, R.B.; MORAES, I.G.This study evaluated the marginal adaptation of apical plug fabricated with three types of endodontic sealers in roots with apical foramen enlarged. Ninety single-rooted teeth with a single canal were used. The root canals were prepared by crown-down technique with Gates Glidden burs in decreasing order, from bur #5 to #1. After this procedure, the root canals were enlarged with K files #50 to #90. Following, the teeth were divided into 3 groups of 30 specimens each, according to the materials employed to fabricate the 5-mm-thick apical plugs: group 1 \u2013 Gray MTA-Angelus\u00ae; group 2 \u2013 CPM\u00ae and grupo 3 \u2013 MBPc sealer. Lateral condensation technique was used for obturation and each properly labeled, subgroup was placed in an oven at 37 \u00b0C for 48 hours. After, the teeth were longitudinally worn with carborundum discs, gold-sputtered and analyzed by scanning electron microscopy, recording SEM micrographs at 35X and 150X magnifications. For analysis of the marginal adaptation of sealers, the SEM micrographs at 35X magnification were analyzed by the Image Tool 3.0 software and the extension of misfit was measured linearly, in micrometers. The results were tabulated and analyzed statistically by Kruskal-Wallis and Dunn's tests with a significant level of 5%. CPM\u00ae sealer had better results though without statistically significant difference.265elcia_mvs@hotmail.com); REPEKE, C.E.; TROMBONE, A.P.F.; FERREIRA-JR, S.B.; MARTINS JR, W.; GARLET, G.P.SILVEIRA, E.M.V. levels, which can be due genetic polymorphisms and/or specific periodontopathogens. This study investigated the influence of genetic (MMP1-1607 SNP) and microbial factors in the determination of MMP-1 mRNA levels in periodontal tissues of chronic periodontitis CP (N=178) and control C (N=190) groups. MMP1-1607 SNP was investigated by PCR-RFLP, while the MMP-1 mRNA levels and the periodontopathogens presence and load were determined by RealTime-PCR. No significant differences were found in the frequency of MMP1-1607 genotypes in C and CP groups. In healthy tissues MMP1-1607 2G allele was associated with higher MMP-1 levels while in CP MMP-1 levels were associated with the presence and load of periodontopathogens, and also with TNF-\u00e1 and IL-1\u00e2 expression irrespective of MMP1-1607 genotype. In vitro data demonstrate that 2G macrophages low and intermediate dose LPS and TNF-\u00e1+IL-1\u00e2 stimulation was associated with increased MMP-1 expression, while strong and repeated stimulation resulted in higher MMP-1 levels irrespective of MMP1-1607 genotype. Our data demonstrate a limited role for MMP1-1607 SNP in periodontitis, where the extensive chronic antigenic challenge exposure overcome the genetic control and plays a major role in determination of MMP-1 expression.266lencristina.v.c@hotmail.com); SALLUM, A.W.; SILVA, C.O.CAMARGO, E.C.V. shrinkage and on the repair of the graft donor area. Ten smokers and twelve non-smokers patients, with <1mm of attached gingiva associated with oral hygiene deficiency, high frenulum attachment or gingival recession were selected to receive FGG for keratinize tissue augmentation. The clinical parameters of probing depth (PD), gingival margin level (GML), clinical attachment level (CAL), keratinized tissue (KT), gingival thickness (Tkn), and FGG high, length, and area were evaluated. The palate donor area was evaluated by immediate bleeding (IB) and complete wound epithelialization (CE). The parameters were evaluated before surgery, 7, 15, 30, 60, and 90 days postsurgery. The outcomes of the present study show that, instead of the absence of statistically significant difference between smokers and non-smokers, there is a tendency for a negative impact of tobacco smoking. At 3 months postsurgery, the percentage of shrinkage of FGG area, high, and length in smokers was greater than in non-smokers , but there was no statistically significant difference. The final amount of KT increased in both groups, but was slightly smaller in smokers (4.91mm) than in non-smokers (5.49mm). A smaller percentage of smoker patients presented immediate bleeding than non-smoker patients , the same occurred with complete wound epithelialization at 15 days postsurgery. Within the limits of the present study, it may be concluded that FGG is an adequate technique for keratinized tissue augmentation in both smokers and non-smokers. Cigarette smoking interferes with palate epithelialization and bleeding, however, it does not have a negative impact on the clinical outcomes of FGG shrinkage.267emilene.mc@bol.com.br); VIEIRA, A.E.M.; DELBEM, A.C.B.; DANELON, M.; CANNON, M.; STOCK, S.R.MISSEL, E.M.C. were selected through surface hardness analysis. Five impressions spaced 100 \u03bcm from each other were made at 300 and 600 \u03bcm from the edge. Specimens (n=10) were prepared from 5 materials: sealant with ACP, sealant with ACP and F , sealant with F, sealant without F, and a resin-modified glass-ionomer. Next, the specimens attached to the enamel blocks were individually subjected to a pH-cycling model to promote demineralization . Surface hardness was measured again at 300 and 600 \u03bcm from the enamel/sealant interface. Synchrotron XMT was performed to analyze the lesion profile and to calculate the mineral concentration (gHAp cm-3) at each 2.8 \u03bcm, starting at the surface up to 221.2 \u03bcm. The highest mineral content in the first layer of enamel was found in the group of products with anti-caries ions. Specimens of sealant with no F and sealant with ACP led to the lowest mineral content when analysis was performed at the bottom of the caries lesion. The results of this 268eriverp@yahoo.com.br); MACEDO, A.P.; PISANI, M.X.; PARANHOS, H.F.O.; SILVA-LOVATO, C.H.PEREIRA, E.E.S.S. and three for complete dentures: Corega\u00ae, Experimental 1 (Zonil), Experimental 2 (Chloramine T). Brushes with 26 soft tufts of bristles of 0.25 mm in diameter and 10mm in height were used. The assay was performed brushing with the aid of a machine of type Pepsodent, in which the dental brushes aid to suspension of dentifrices brushing the specimens of acrylic resin (Plex-glass). For each test were used 06 brushes for each specimen. The time used for brushing was 50 minutes . After the assay, the brushes were removed, washed and dried with absorbent paper sheets. For analysis of bristles, 10 brushes were separated from each group: water, Experimental 1, Experimental 2, Corega\u00ae and Sorriso\u00ae. As a control, were used bristles of brush not tested. Of each bristle of brush was withdrawn a total of 10 bristles per group. Then, the bristles were placed in a Plex-glass plate so that all of them were in the same plane. Measurement of the diameter was performed in a profilometer accurate to tenths of millimeters (0.01 mm) at 0.02 mm from the tip of the bristle. Ten values for each combination (toothbrush and dentrifices) tested were obtained. Data analysis was performed using the ANOVA (P <0.05). The results indicated that only the group Sorriso\u00ae (0.15 \u00b1 0.02) when compared with the control group (0.2 \u00b1 0.02) showed statistical significance (P = 0.0117), while the other examined groups showed no statistically significant values. All dentifrices promoted changes on the end of bristles, but Sorriso\u00ae caused, statistically, the greatest changes.269erica.fobusp@yahoo.com.br); MOLON, R.S.; GABRIELLI, M.F.R.; GABRIELLI, M.A.C.; HOCHULI-VIEIRA, E.AVILA, E.D. ; SALLES, M.A.; ARAKAWA, A.M.; BASTOS, R.S.; CALDANA, M.L.; BASTOS, J.R.M.SITTA, E.I. with pressing dental. The patient attended 15 sessions speech therapy for, including specific approaches of orofacial movement and mobility, guidelines for care in cleaning and protecting the skin, quality of daily diet and the importance of sleep and well being. Having knowledge of the patient's inadequate facial expressions habits, therapies aimed at the muscle harmonization as well as massages for relaxation and wrinkle smoothing were performed. The facial discomfort was resolved by removal of the tooth clenching habit with the help of the minimization of the points of tension and both articular and muscle pain, as well as changes in the masticatory pattern and quality of life, improving the harmony of both hemi-faces. It is concluded that the benefits of the adequation of the orofacial muscles and stomatognathic functions provided together with the balance of form and function a sensitive rejuvenation.271carvalho.odonto@gmail.com); RODRIGUES, L.M.V.; SALES-PERES, S.H.C.; HORTENSE, S.R.; SALES-PERES, A.C.; SALES-PERES, A.CARVALHO, E.S. ; MAIA, L.P.; LUCIA, C.I.; SOUSA, S.L.S.; REINO, D.M.SILVA, E.R. ; FERNANDES, L.A.; MURAKAWA, A.C.; BOSCO, A.F.; GOUVEIA, V.G.GUALBERTO J\u00daNIOR, E.C. Soft tissue pedicle graft (2) Soft tissue free graft. Following Miller's classification, total coverage of Class I and Class II defects is perfectly predictable, Class III defects will result in a partial coverage and Class IV defects will not be covered due to advanced interdental loss of bone and soft tissue proximity. We will tell a clinical case of a patient of feminine gender, 28 years old, that presented loss of the interdental papilla among the teeth 21 and 22 with Miller's Class III gingival retraction caused by localized periodontitis. The radiographic exam suggested vertical bone loss from middle to the apical root third. After basic periodontal treatment, laterally positioned flap was elevated with connective tissue graft in order to increase root coverage and reconstitute the interdental papila. The postoperative follow up showed partial root coverage and increase of the soft tissue thickness in the interdental papilla. Six months after this intervention, a second surgical procedure was accomplished using the tunnelization technique and subepitelial connective tissue graft aiming to improve even more the esthetic results obtained. The 1-month postoperative evaluation showed increase of root coverage and interdental papilla reconstitution. The proximal faces of teeth #21 and #22 were restored to mask the \u201cblack space\u201d.274evertonjs2@hotmail.com); MUNCINELLI, E.A.G.; OLIVEIRA, R.M.W.SILVA, E.J. ; SANTOS, F.Z.C.; HON\u00d3RIO, H.M.; MAGALH\u00c3ES, A.C.; BUZALAF, M.A.R.; RIOS, D.SANTOS, F.Z. (Fabiana Zaidan Cardoso dos Santos - FAPESP (Proc. 2007/07296-1).in situ/ex vivo study evaluated whether the type of cola drink (regular or light) could influence the wear of bovine enamel subjected to erosion followed by brushing abrasion. During an experimental 7-day phase, 10 previously selected volunteers wore intraoral palatal devices, with 8 bovine blocks which were subjected to four groups: (ER) erosion with regular cola, (EAR) erosion + abrasion with regular cola, (EL) erosion with light cola and (EAL) erosion + abrasion with light cola. During 7 days, half of the palatal device was immersed in light cola drink (4 blocks) for 5 min and 2 blocks were brushed using a fluoride dentifrice. Immediately after, the other half of the appliance was immersed in regular cola drink and the brushing procedures were repeated. The pH and phosphorus, calcium and fluoride concentrations were analyzed using standard procedures . The amount of base (NaOH 0.2 M) added to raise the pH to 7.0 was 0.125 mL for both colas. Enamel alterations were measured using wear profile tests (mm). The data were analyzed by ANOVA and Tukey's test (p<0.05). The light cola drink (EL-0.36/EAL-0.39) promoted less wear than the regular one (ER-0.72/EAR-0.95) for both conditions (erosion and erosion + abrasion). There was no difference between erosion and erosion + abrasion for the light cola drink; however for the regular cola drink the erosion resulted in less wear when compared to erosion + abrasion. The data suggest that the light cola drink promoted less enamel wear even when erosion was followed by brushing abrasion.This 276fabioantonio_7@hotmail.com); NERI, N.B.D.; SAMPIERI, M.B.S.; DIAS-RIBEIRO, E.; SANT'ANA, E.; FERREIRA J\u00daNIOR, O.RIZZANTE, F.A.P. ; SILVA, A.S.C.; BERRETIN-FELIX, G.YOSHIDA, F.S. ; AGUIAR, S.M.H.C.A.DIOGO, F.S.F. ; PAIVA, R.C.; BATISTA D.E.; CARVALHO, M.L.; ARCIERI, R.M.CUNHA, F.G. registered at CROMG in the city of Uberl\u00e2ndia. Questionnaires were applied in the form of interviews to 69 individuals, randomly selected 43 professionals and 26 students from 1st and 2nd year, who agreed to participate in this study. The results showed that age ranged from 19 to 42 years for students and 23 to 63 years for the professionals. In relation to the work received, it was observed that both groups were evaluated molds and models kindness 42.30% (students) and 37.20% (DPT). The question \u201cThe profession of DPT offers risk of diseases that can be acquired at work?\u201d The majority of respondents answered that yes. Regarding the question: which diseases offer risk of infection? For students and DPTs, the main infectious diseases were AIDS (18.60% and 16.07% respectively) and hepatitis (48.83% and 58.92% respectively) and the form of acquiring these diseases was consensual for both groups: \u201ccontaminated impressions\u201d. Personal protective equipments were used by 96.15% of students and 93.02% of DPTs. Of the respondents, 79.71% were vaccinated to avoid contracting diseases. The occurrence of accidents at work was evident in 47.82% of participants, cutting and drilling being the most frequent causes. Based on these results, we can conclude that although both groups of respondents were aware of the risk that the profession of DPT offers, students have more information about it."} +{"text": "In our original research article, there is an error in one of the references cited.South Asian J. Exp. Biol. 5, 271\u2013282\u201d should be instead cited as:The reference \u201cSharma, S., Assam, T., Meghvansi, M., Vairale, M., Organis, D., Veer, V., et al. (2015). Cellulase enzyme based biodegradation of cellulosic materials: an overview. South Asian J. Exp. Biol. 5, 271\u2013282.\u201d\u201cChatterjee, S., Sharma, S., Prasad, R. K., Datta, S., Dubey, D., Meghvansi M. K., et al. (2015). Cellulase enzyme based biodegradation of cellulosic materials: an overview. The authors apologize for the mistake. This error does not change the scientific conclusions of the article in any way.The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Scientific Reports6: Article number: 3352510.1038/srep33525; published online: 09162016; updated: 11112016Jongwan Choi was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Information file.The author contributions section now reads:\u201cI.K.M. and J.O. designed the research and initiated the study. I.K.M., S.Y. B.K. and J.C. prepared and characterized the material. All authors contributed to the discussion\u201d"} +{"text": "Table of ContentsThe contribution of microbial biotechnology to sustainable development goalsK. Timmis, W. M. de Vos, J. L. Ramos, S. E. Vlaeminck, A. Prieto, A. Danchin, W. Verstraete, V. de Lorenzo, S. Y. Lee, H. Br\u00fcssow, J. K. Timmis and B. K. Singh 984Microbial technology with major potentials for the urgent environmental needs of the next decadesW. Verstraete and J. de Vrieze 988Seven microbial bio\u2010processes to help the planetV. de Lorenzo 995SDG 2: End hunger, achieve food security and improved nutrition and promote sustainable agricultureTiny microbes, big yields: enhancing food crop production with biological solutionsP. Trivedi, P. M. Schenks, M. D. Wallenstein and B. K. Singh 999Increased nutritional value in food cropsN. Goicoechea and M. C. Antol\u00edn 1004Beneficial microbial signals from alternative feed ingredients: a way to improve sustainability of broiler production?F. Van Immerseel, V. Eeckhaut, R. J. Moore, M. Choct and R. Ducatelle 1008Biofloc technology application in aquaculture to support sustainable development goalsP. Bossier and J. Ekasari 1012Microalgae, old sustainable food and fashion nutraceuticalsJ. L. Garcia, M. de Vicente and B. Gal\u00e1n 1017Hunger and microbiology: Is a low gastric acid\u2010induced bacterial overgrowth in the small intestine a contributor to malnutrition in developing countries?S. A. Sarker, T. Ahmed and H. Br\u00fcssow 1025Goal 3. Ensure healthy lives and promote well\u2010being for all at all agesMicrobially derived biosensors for diagnosis, monitoring and epidemiologyH.\u2010J. Chang, P. L. Voyvodic, A. Z\u00fa\u00f1iga and J. Bonnet 1031Roads to advanced vaccines: influenza case studyP. Riese and C. A. Guzm\u00e1n 1036Infection therapy: the problem of drug resistance \u2013 and possible solutionsH. Br\u00fcssow 1041Microbial approaches for targeting antibiotic\u2010resistant bacteriaW. F. Wong and M. Santiago 1047Strategies for combating persister cell and biofilm infectionsT. K. Wood 1054Sustainable therapies by engineered bacteriaB. \u00c1lvarez and L. \u00c1. Fern\u00e1ndez 1057Metal\u2010based antimicrobial strategiesR. J. Turner 1062The contribution of microbial biotechnology to sustainable development goals: microbiome therapiesP. W. O'Toole and M. Paoli 1066Synbiotic approaches to human health and well\u2010beingT. Gurry 1070Tumor\u2010targeting bacteria\u2010based cancer therapies for increased specificity and improved outcomeS. Felgner, V. Pawar, D. Kocijancic, M. Erhardt and S. Weiss 1074Hygiene: microbial strategies to reduce pathogens and drug resistance in clinical settingsE. Caselli 1079The DIY Digital Medical CentreJ. K. Timmis and K. Timmis 1084Goal 6. Ensure availability and sustainable management of water and sanitation for allMicrobial biotechnologies for potable water productionS. J. Fowler and B. F. Smets 1094Current and future microbiological strategies to remove As and Cd from drinking waterJ. M. Byrne and A. Kappler 1098Microbial biotechnology and circular economy in wastewater treatmentP. H. Nielsen 1102Controlling cyanobacterial harmful blooms in freshwater ecosystemsH. W. Paerl 1106Goal 7. Ensure access to affordable, reliable, sustainable and modern energy for allGreen biofuels and bioproducts: bases for sustainability analysisJ. L. Ramos, F. Garc\u00eda\u2010Lorente, M. Valdivia and E. Duque 1111Bioelectricity (electromicrobiology) and sustainabilityK. H. Nealson 1114Advances and bottlenecks in microbial hydrogen productionA J. Stephen, S. A. Archer, R. L. Orozco and L. E. Macaskie 1120BiogasC. M. Plugge 1128Fungal nanoscale metal carbonates and production of electrochemical materialsQ. Li and G. M. Gadd 1131Goal 8. Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for allThe contribution of microbial biotechnology to economic growth and employment creationK. Timmis, V. de Lorenzo, W. Verstraete, J. L. Ramos, A. Danchin, H. Br\u00fcssow, B. K. Singh and J. K. Timmis 1137Goal 11. Make cities and human settlements inclusive, safe, resilient and sustainableMicrobial biotechnology approaches to mitigating the deterioration of construction and heritage materialsP. Junier and E. Joseph 1145Microbial communities as biosensors for monitoring urban environmentsF. Ling 1149Bioprotection of the built environment and cultural heritageG. M. Gadd and T. D. Dyer 1152Architects of nature: growing buildings with bacterial biofilmsM. Dade\u2010Robertson, A. Keren\u2010Paz, M. Zhang and I. Kolodkin\u2010Gal 1157Goal 12. Ensure sustainable consumption and production patternsThe future of biologically inspired next\u2010generation factories for chemicalsC. Schmidt\u2010Dannert 1164Gas fermentation for commodity chemicals and fuelsF. R. Bengelsdorf and P. D\u00fcrre 1167Metallic bionanocatalysts: potential applications as green catalysts and energy materialsL. E. Macaskie, I. P. Mikheenko, J. B. Omajai, A. J.Stephen, and J. Wood 1171Bacterial cellulose as an example product for sustainable production and consumptionW. D. Jang, J. H. Hwang, H. U. Kim, J. Y. Ryu and S. Y. Lee 1181Microbial melanins for radioprotection and bioremediationR. J. B. Cordero, R. Vij and A. Casadevall 1186Biomining of metals: how to access and exploit natural resource sustainablyC. A. Jerez 1191Recovery of precious metals from waste streamsJ. He and A. Kappler 1194Metal and metalloid biorecovery using fungiX. Liang and G. M. Gadd 1199How to access and exploit natural resources sustainably: petroleum biotechnologyA. Sherry, L. Andrade, A. Velenturf, B. Christgen, N. D Gray and I. M. Head 1206The contribution of microbially produced nanoparticles to sustainable development goalsM. E. Cueva and L. E. Horsfall 1212Goal 13. Take urgent action to combat climate change and its impacts2 surplus that nature, per se, is not capable of fixingAbout how to capture and exploit the COM. S. Godoy, B. Mongili, D. Fino and M. A. Prieto 1216Harnessing microbiome\u2010based biotechnologies for sustainable mitigation of nitrous oxide emissionsH.\u2010W. Hu, J.\u2010Z. He and B. K. Singh 1226Goal 14. Conserve and sustainably use the oceans, seas and marine resources for sustainable developmentMicrobial biotechnology addressing the plastic waste disasterT. Narancic and K. E. O'Connor 1232The contribution of microbial biotechnology to mitigating coral reef degradationK. Damjanovic, L. L. Blackall, N. S. Webster and M. J. H. van Oppen 1236Goal 15. Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertification, and halt and reverse land degradation and halt biodiversity lossSoil and brownfield bioremediationM. Megharaj and R. Naidu 1244Microbial biotechnology as a tool to restore degraded drylandsF. T. Maestre, R. Sol\u00e9 and B. K. Singh 1250Enabling Technologies of microbial approaches towards attainment of sustainable development goalsSystems metabolic engineering as an enabling technology in accomplishing sustainable development goalsD. Yang, J. S. Cho, K. R. Choi, H. U. Kim and S. Y. Lee 1254The contribution of bacterial genome engineering to sustainable developmentD. R. Reu\u00df, F. M. Commichau and J. St\u00fclke 1259Synthetic microbiology: from analogy to methodologyV. de Lorenzo 1264Bioprocess scale\u2010up/down as integrative enabling technology: from fluid mechanics to systems biology and beyondF. Delvigne, R. Takors, R. Mudde, W. van Gulik and H. Noorman 1267"} +{"text": "Cichlidogyrus Paperna, 1960. Yet, only 24 species were described from Tanganyikan hosts and some host tribes have never been investigated for monogeneans. This study presents the first parasitological examination of species of the tribes Cyprichromini ), Eretmodini and Ectodini ). Specimens of the ectodine Ophthalmotilapia nasuta from which four Cichlidogyrus spp. have been previously described from more southern localities were also studied. Further, we discuss the haptor configuration in Tanganyikan Cichlidogyrus spp. and highlight the morphological diversity of the vagina, and that of the heel, a sclerotized part of the male copulatory organ, absent in some species of Cichlidogyrus.Lake Tanganyika harbours the most diverse cichlid assemblage of the Great African Lakes. Considering its cichlid flocks consist of approximately 250 endemic species, we can hypothesize a high species-richness in their often quite host-specific monogenean ectoparasites belonging to Cichlidogyrus spp. were isolated from gills and fixed using GAP. Haptoral and genital hard parts were measured and drawn by means of a phase contrast microscopic examination.Cichlidogyrus milangelnari n. sp. on C. microlepidotus; C. jeanloujustinei n. sp. on E. marksmithi; C. evikae n. sp. on T. irsacae; C. aspiralis n. sp., C. glacicremoratus n. sp. and C. rectangulus n. sp. on O. nasuta; and C. pseudoaspiralis n. sp. and C. discophonum n. sp. on A. dewindti. Three haptoral morphotypes were recognized among the new species. Species of Cichlidogyrus from closely related hosts exhibited the same morphotypes. Geographical variation in Cichlidogyrus spp. fauna as observed in O. nasuta and three morphotypes were distinguished. Finally, we listed 111 Cichlidogyrus species, of which 27 and three Tanganyikan species lack sclerotized vagina and heel, respectively, just like 19 and seven species outside of the lake.We describe eight new species: Cichlidogyrus fauna reflect the phylogenetic relationships of their cichlid hosts. It seems that several lineages of Cichlidogyrus spp. exist in Lake Tanganyika but further studies are necessary to confirm this hypothesis and answer questions related to Lake Tanganyika and its cichlids.Haptoral and genital features in the Tanganyikan The online version of this article (10.1186/s13071-017-2460-6) contains supplementary material, which is available to authorized users. Cichlidogyrus discophonum n. sp. resembles C. makasai, a gill parasite of the ectodine cichlids O. nasuta, O. boops and O. ventralis [C. makasai by (i) the absence of a heel (vs pronounced heel in C. makasai), (ii) the length of the copulatory tube (41\u201347 vs 69\u201379\u00a0\u03bcm), and (iii) the shape of the accessory piece . Cichlidogyrus discophonum n. sp. is easily distinguishable from C. vandekerkhovei . In addition, C. discophonum n. sp. lacks a heel unlike C. vandekerkhovei.r, 1898) by the mentralis ) in haviType-host:Aulonocranus dewindti Fig. ; tribe EType-locality: Nyaruhongoka , Lake Tanganyika, Burundi.Type-material: Holotype: MRAC_vermes_37944. Paratypes: MRAC_vermes_37955; MNHN HEL587; SAMC-A088699.Site in host: Gills.Prevalence and intensity of infection: 33% (1/3); 1\u20138 monogeneans per infected host.ZooBank registration: To comply with the regulations set out in article 8.5 of the amended 2012 version of the International Code of Zoological Nomenclature (ICZN) [zoobank.org:pub:3B9F16F6-8E3F-44F5-8D5D-B1D4A4754242. The LSID for the new name Cichlidogyrus pseudoaspiralis is urn: urn:lsid:zoobank.org:act:F69F41FB-C806-40E4-99F0-7FE8BA1FBCC7.e (ICZN) , detailsEtymology: The specific epithet is the combination of the Latin prefix \u201cpseudo\u201d and \u201caspiralis\u201d, referring to the similarity of the new species to C. aspiralis n. sp. described above.n\u2009=\u20093) long, 113\u2013129 wide at mid-body. Dorsal anchors with short shaft and elongated guard (c.5 times length of shaft) and short, slightly bent blade and curved point: a\u2009=\u200937\u201342 ; b\u2009=\u200927\u201328 ; c\u2009=\u20092\u20134 ; d\u2009=\u200913\u201316 ; e\u2009=\u20096\u20137 . Dorsal bar straight, thick, long with short appendages of anterior face of dorsal transverse bar: h\u2009=\u20096\u20137 ; w\u2009=\u20094\u20136 ; x\u2009=\u200931\u201332 ; y\u2009=\u200914\u201315 . Ventral anchors with shaft shorter than guard, blade longer than in dorsal anchors, with arched point: a\u2009=\u200937\u201340 ; b\u2009=\u200934\u201337 ; c\u2009=\u20092\u20134 ; d\u2009=\u20099\u201311 ; e\u2009=\u200910\u201311 . Ventral bar V-shaped: w\u2009=\u20093\u20134 ; x\u2009=\u200930\u201332 . Hook pair I with well-developed shank, long in comparison with remaining pairs which are similarly short (sensu [n\u2009=\u20093) long, pair II\u2009=\u200920\u201322 long, pair III\u2009=\u200921\u201323 long, pair IV\u2009=\u200921\u201324 long, pair V\u2009=\u200910\u201312 long, pair VI\u2009=\u200915\u201316 long, and pair VII\u2009=\u200917\u201318 long. Male copulatory organ beginning in ovoid bulb, with relatively long, curved and thin copulatory tube: MCO\u2009=\u200952\u201356 ; Ct\u2009=\u200940\u201343 . Heel long, straight, He\u2009=\u200914\u201317 . Accessory piece thin, straight, proximally with thin elbow-shaped connection to copulatory tube, Ap\u2009=\u200926\u201331 . Vagina non-sclerotized.[Based on 8 specimens fixed in GAP; Fig.\u00a0C. pseudoaspiralis n. sp. belongs to the group of Cichlidogyrus spp. characterized by a long hook pair I and short pairs II-IV, VI and VII and the relatively straight heel. However, it is easily distinguished from C. aspiralis n. sp. by (i) the shorter dorsal (31\u201332 vs 45\u201347\u00a0\u03bcm) and ventral bars (30\u201332 vs 37\u201340\u00a0\u03bcm), (ii) the longer copulatory tube (40\u201343 vs 20\u201321\u00a0\u03bcm), (iii) the longer accessory piece (26\u201331 vs 14\u201319\u00a0\u03bcm), and (iv) the vagina . Further, as in C. aspiralis n. sp., the dorsal bar in C. pseudoaspiralis n. sp. is similar to that exhibited by the monogenean species of the tylochromine cichlid hosts (see above). Thus, the new species is mainly distinguishable from C. muzumanii by (i) the differently sized and shaped dorsal bar (31\u201332 vs 45\u201362\u00a0\u03bcm), (ii) the copulatory tube , (iii) the heel (14\u201317 vs 4\u20137\u00a0\u03bcm in C. muzumanii), and (iv) the accessory piece . In addition, like C. aspiralis n. sp., C. pseudoaspiralis n. sp. is easily distinguishable from C. centesimus by the absence of a spiral in the copulatory tube and the presence of an accessory piece (see above). Further, the new species is distinguishable from C. casuarinus by (i) the shorter dorsal (37\u201342 vs 52\u201364\u00a0\u03bcm) and ventral anchors (37\u201340 vs 47\u201359\u00a0\u03bcm), (ii) the shorter dorsal (31\u201332 vs 64\u201385\u00a0\u03bcm) and ventral bars (30\u201332 vs 54\u201367\u00a0\u03bcm), (iii) the hook pair I (long and well developed vs long but not thick), (iv) the shorter heel (14\u201317 vs 40\u201359\u00a0\u03bcm), (v) the longer and differently shaped copulatory tube , and (vi) the sclerotized vagina (present in C. casuarinus).The new species VII (see ), a copuVII (see ). This get, 1995 ; C. berret, 2003 ; C. dionna, 1968 ; C. halina, 1969 ; C. muzule, 2012 ; C. nuniet, 1998 ; C. paperd, 1969 ; C. philou, 1993 ; C. quaeou, 1993 ; C. reveet, 2003 ; and C. et, 1996 . CichlidCichlidogyrus described herein belong to three morphological groups according to the relative length of their haptoral hook pairs following Pariselle & Euzet [C. milangelnari n. sp. . The closely related C. aspiralis n. sp. possess a characteristic hook configuration with a thin hook pair I and long pairs II-IV, VI and VII [Cichlidogyrus rectangulus n. sp. [C. kothiasi showing well developed and long pair I with resembling pairs II-IV, VI and VII in size [C. chrysopiformis Pariselle, Bitja Nyom & Bilong Bilong, 2013 from T. bemini Thys van der Audenaerde, 1972, with hook pair I of medium size, but not large, and short pairs II-IV, VI and VII [The new species of & Euzet , and Vig & Euzet . As alresp. Fig. , C. jeansp. Fig. , C. eviksp. Fig. , C. glacsp. Fig. , and C. sp. Fig.\u00a0 belong tsp. Fig. and C. psp. Fig.\u00a0 belong t48) , C. koth in size , and fin and VII .Cichlidogyrus (including the new species described in this study) is provided is non-sclerotized. Within the first haptoral group , we listed 18 non-Tanganyikan species exhibiting a sclerotized vagina. These are C. acerbus Dossou, 1982 [C. amieti Birgi & Euzet, 1983 [C. amphoratus Pariselle & Euzet, 1996 [C. berrebii Pariselle & Euzet, 1994 [C. cirratus Paperna, 1964 [C. cubitus Dossou, 1982 [C. djietoi [C. giostrai Pariselle, Bilong Bilong & Euzet, 2003 [C. karibae Dou\u00ebllou, 1993 [C. levequei Pariselle & Euzet, 1996 [C. louipaysani Pariselle & Euzet, 1995 [C. mvogoi Pariselle, Bitja Nyom & Bilong Bilong, 2014 [C. njinei Pariselle, Bilong Bilong & Euzet, 2003 [C. ornatus Pariselle & Euzet, 1996 [C. pouyaudi Pariselle & Euzet, 1994 [C. sclerosus Paperna & Thurston, 1969 [C. slembroucki Pariselle & Euzet, 1998 [C. zambezensis Dou\u00ebllou, 1993 [C. mbirizei Muterezi Bukinga, Vanhove, Van Steenberge & Pariselle, 2012, possesses a sclerotized vagina [C. casuarinus, C. centesimus and C. nshomboi, belonging to none of the morphological groups (see above) were originally described lacking a sclerotized vagina. Later, this feature has been reported by Pariselle et al. Unlike C. rectangulus n. sp. and C. sturmbaueri showing the last hook configuration , all Cichlidogyrus spp. described so far belonging to this morphological group possess a sclerotized vagina. These are C. aegypticus Ergens, 1981 [C. agnesi Pariselle & Euzet, 1995 [C. anthemocolpos Dossou, 1982 [C. bilongi Pariselle & Euzet, 1995 [C. bonhommei Pariselle & Euzet, 1998 [C. bouvii Pariselle & Euzet, 1997 [C. dossoui Dou\u00ebllou, 1993 [C. douellouae Pariselle, Bilong Bilong & Euzet, 2003 [C. ergensi Dossou, 1982 [C. flexicolpos Pariselle & Euzet, 1995 [C. gallus Pariselle & Euzet, 1995 [C. gillesi Pariselle, Bitja Nyom & Bilong Bilong, 2013 [C. guirali Pariselle & Euzet, 1997 [C. hemi Pariselle & Euzet, 1998 [C. kouassii N\u2019Douba, Thys van den Audenaerde & Pariselle, 1997 [C. legendrei Pariselle & Euzet, 2003 [C. lemoallei Pariselle & Euzet, 2003 [C. microscutus Pariselle & Euzet, 1996 [C. ouedraogoi Pariselle & Euzet, 1996 [C. paganoi Pariselle & Euzet, 1997 [C. testificatus Dossou, 1982 [C. thurstonae Ergens, 1981 [C. tiberianus Paperna, 1960 [C. vexus Pariselle & Euzet, 1995 [Based on the original descriptions and the systematic review of African monogenean species published by Pariselle & Euzet , an overou, 1982 ; C. amieet, 1983 ; C. amphet, 1996 ; C. berret, 1994 ; C. cirrna, 1964 ; C. cubiou, 1982 ; C. djie djietoi ; C. gioset, 2003 ; C. kariou, 1993 ; C. leveet, 1996 ; C. louiet, 1995 ; C. mvogng, 2014 ; C. njinet, 2003 ; C. ornaet, 1996 ; C. pouyet, 1994 ; C. scleon, 1969 ; C. slemet, 1998 ; and C. ou, 1993 . From Lad vagina . The thrns, 1981 ; C. agneet, 1995 ; C. anthou, 1982 ; C. biloet, 1995 ; C. bonhet, 1998 ; C. bouvet, 1997 ; C. dossou, 1993 ; C. doueet, 2003 ; C. ergeou, 1982 ; C. flexet, 1995 ; C. gallet, 1995 ; C. gillng, 2013 ; C. guiret, 1997 ; C. hemiet, 1998 ; C. kouale, 1997 ; C. legeet, 2003 ; C. lemoet, 2003 ; C. micret, 1996 ; C. ouedet, 1996 ; C. pagaet, 1997 ; C. testou, 1982 ; C. thurns, 1981 ; C. tibena, 1960 ; and C. et, 1995 . Fu. FuCichlped heel , 49, 56.Cichlidogyrus spp. As already mentioned, the number of species of Cichlidogyrus studied and described so far remains small compared to the extraordinary diversity of their potential cichlid hosts in Lake Tanganyika.Monogeneans are an ideal group of organisms for studying evolutionary mechanisms because of their remarkable species richness, morphological diversity and wide distribution . They deCichlidogyrus spp. which are described herein. Three of these cichlid species belong to tribes that were not previously investigated for the presence of monogeneans, i.e. the cyprichromine C. microlepidotus and the eretmodines E. marksmithi and T. irsacae; these are new host records for representatives of Cichlidogyrus. Three species of Cichlidogyrus were described from these cichlids: C. milangelnari n. sp. from C. microlepidotus, C. jeanloujustinei n. sp. from E. marksmithi and C. evikae n. sp. from T. irsacae. Several haptoral , as well as some general copulatory organ characteristics clearly suggest an affinity between C. jeanloujustinei n. sp. and C. evikae n. sp., and therefore reflect the phylogenetic relationship between their hosts E. marksmithi and T. irsacae, both belonging to the tribe Eretmodini. Similar observations, i.e. the morphological similarity of the sclerotized parts of closely related Tanganyikan Cichlidogyrus spp. have been reported for tropheine hosts and host choice was clearly associated to phylogenetic relatedness of the cichlid hosts [Our investigation of five cichlid species from the Burundi coast revealed eight new id hosts , 42, 65.C. pseudoaspiralis n. sp. and C. aspiralis n. sp. on A. dewindti and O. nasuta, respectively mirrors the relatedness between the two hosts, both belonging to the tribe Ectodini [Cichlidogyrus spp. exhibit the same morphotype and similarities in the shape and/or size of the sclerotized structures are mainly visible in the ventral and dorsal anchors, the hook pairs and the heel in the MCO (see diagnoses and drawings). Intraspecific variability was reported in the heel length of C. centesimus, a species exhibiting the same morphotype as the two new species described here, i.e. C. aspiralis n. sp. and C. pseudoaspiralis n. sp. [C. pseudoaspiralis n. sp., make it distinct from C. aspiralis n. sp.Furthermore, the distribution of the morphologically similar new species Ectodini . Indeed,s n. sp. . HoweverO. nasuta in Burundi revealed the presence of three new monogenean species i.e. C. aspiralis n. sp., C. glacicremoratus n. sp. and C. rectangulus n. sp.: these were well differentiated from the four species previously described by Vanhove et al. [O. nasuta and its congeners , and a MCO with a straight heel. The morphotype of C. discophonum n. sp., C. glacicremoratus n. sp., C. makasai and C. vandekerkhovei displays short hook pairs and a dorsal bar with long auricles. The morphotype represented by C. rectangulus n. sp. and C. sturmbaueri presents a curved dorsal bar, long hook pairs II-IV, VI and VII and a MCO with a short copulatory tube associated to an h-shaped accessory piece.Our study of e et al. on O. naCichlidogyrus spp. isolated from Ophthalmotilapia in Burundi and its congeners from southernmost localities Uvira (D.R. Congo) where the holotype was caught, (ii) the Burundese shore (similar to the Uvira population), (iii) the Ubwari Peninsula (Eastern D.R. Congo) and further south to Kalemie (D.R. Congo), (iv) south of Kalemie along the western shore as far as Chimba in Zambia with a small isolated population at Cape Nangu across Cameron Bay, and (v) Zambian and Tanzanian waters which harbour the widest range of all Ophthalmotilapia spp. [Cichlidogyrus fauna in Burundese O. ventralis follows a similar geographical variation in community composition as found for O. nasuta. In addition, the endemic O. heterodonta inhabiting various localities in the northern and central parts of Lake Tanganyika is the only species of this genus that has never been investigated for its parasite fauna. A study of gill ectoparasites on this cichlid host may provide additional data on the lake\u2019s parasite species diversity. Moreover, it has been reported that Ophthalmotilapia spp. show low genetic diversity but present a high morphological diversity and colour plasticity, and even morphologically intermediate populations among geographically separated species were found [O. nasuta probably played a role in its Cichlidogyrus spp. speciation and distribution. Few studies have been performed on Cichlidogyrus spp. infecting Tanganyikan cichlids incorporating the diversity among host populations. Cichlidogyrus species richness and assemblage composition in several sympatric Simochromis diagramma and Tropheus moorii Boulenger, 1898 populations in southern Lake Tanganyika (Zambia) was studied by Gr\u00e9goir et al. [Cichlidogyrus spp. and significant variation of the parasite assemblages among sampling sites for T. moorii in contrast to S. diagramma which displayed a less species-rich and more homogeneous parasite fauna. Gr\u00e9goir et al. [The morphological diversity within the newly described es Table is probanganyika , 68. Thenganyika ; Koningsnganyika reportedpia spp. , 71. Thure found . Thus, tr et al. . These ar et al. proposedCichlidogyrus spp. Four different haptoral morphotypes of Cichlidogyrus species have previously been reported [Cichlidogyrus, whereas the morphology of the copulatory organ is more appropriate to distinguish between closely related species [Cichlidogyrus spp. was studied by Pariselle & Euzet [Cichlidogyrus and species later developed large hook pair I and longer pairs II-IV, VI and VII [C. kothiasi within the group of species exhibiting short hook pairs and C. nandidae within the group possessing large pair I and short pairs II-IV, VI and VII. On the other hand, some Tanganyikan and non-Tanganyikan species (see above), with their \u201cnew\u201d hook configurations, were not yet described, and therefore, not included. Therefore, we suggest that there are more than four previously reported haptoral groups. Moreover, due to the incomplete taxonomic coverage, it is still not possible to fully elucidate the evolution of the different haptoral configurations in Cichlidogyrus spp. It would be interesting to re-investigate the structural diversity of the hook pairs in Cichlidogyrus spp. and identify the exact \u201cborders\u201d between the haptoral groups.The present study illustrates the morphological diversity of the sclerotized parts of monogeneans in cichlids from Lake Tanganyika through the new species descriptions and the checklist of Tanganyikan and non-Tanganyikan reported , 23, 38. species , 19, 23. & Euzet and thre & Euzet standard & Euzet proposed and VII , 21. FurCichlidogyrus described so far can be clustered based on the vagina being sclerotized or non-sclerotized. In Cichlidogyrus spp. from Lake Tanganyika the vagina is sclerotized or not (see above). Cichlidogyrus pseudoaspiralis n. sp. isolated from Burundese O. nasuta exhibits a sclerotized vagina unlike the remaining new Cichlidogyrus species described herein. In fact, most Tanganyikan Cichlidogyrus spp. exhibit a non-sclerotized vagina and the haptoral sclerites (morphology of the hook pairs).In addition to the haptoral sclerites, species of Cichlidogyrus spp. allowed us to highlight the high diversity in the heel structure , Ectodini and Boulengerochromini (C. nshomboi) are found exclusively in these species [Examination of all original drawings and descriptions of ry plate , 47. In ry plate . This feB. horii . A clear species , 28, 41.Cichlidogyrus spp. are necessary. The high morphological diversity of haptoral structures and reproductive organs of the new species described herein and other species identified so far confirms the existence of various lineages of Cichlidogyrus in Lake Tanganyika. However, further morphological studies and molecular data are needed to elucidate their origin and evolutionary history.It is too early for conclusions about the role of host-specificity in Lake Tanganyika due to limited data on ectoparasite monogeneans in this system. Further studies to investigate cichlid fishes in the lake for parasites belonging to"} +{"text": "Nature Communications 10.1038/s41467-018-03561-w, published online 03 April 2018Correction to: Sci. Rep. 7, 1\u201313 (2017).\u201d This error has now been corrected in the PDF and HTML versions of the Article.The original version of the Article contained incorrect citation information in reference 67. The reference should read \u201cRussell, A. L., Morrison, S. J., Moschonas, E. H. & Papaj, D. R. Patterns of pollen and nectar foraging specialization by bumblebees over multiple timescales using RFID."} +{"text": "Scientific Reports 10.1038/s41598-017-05115-4, published online 19 July 2017Correction to: This Article contains a typographical error in the Author Contributions section.\u201cR.S. Designed the research. L.T. carried out the simulations and L.R. and R.S. performed the data analysis and wrote the manuscript.\u201dshould read:\u201cR.S. Designed the research. L.T. carried out the simulations and L.T. and R.S. performed the data analysis and wrote the manuscript.\u201d"} +{"text": "Lactobacillus casei, L. delbrueckii, L. fermentum, L. plantarum, and L. pentosus. Antibacterial activities of cell-free supernatants (CFSs) of all the Lactobacillus isolates were estimated through standard agar-well diffusion assay, against commonly occurring food-borne and clinically important human pathogens. None of the lactobacilli cell-free supernatant (CFS) exhibited inhibitory activity against four pathogens, namely Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Klebsiella pneumoniae. Bacillus cereus, Salmonella enterica serovar Typhi, and Shigella flexneri were moderately inhibited by majority of CFSs, whereas, weak activity was observed against Pseudomonas aeruginosa and Proteus mirabilis. CFS of some of the curd isolates displayed antagonistic activity against Streptococcus mutans; however, human milk lactobacilli did not displayed any inhibitory activity against them. As expected, Nisin (Nisaplin\u00ae) showed inhibitory activity against Gram-positive, S. aureus, B. cereus, and L. monocytogenes. Interestingly, few of the examined CFSs exhibited inhibitory activities against both Gram-positive and Gram-negative pathogens. Findings from this study support the possibility to explore the tested lactobacilli and their CFSs as natural bio-preservatives, alone or in combination with approved bacteriocins in food and pharma formulations after validating their safety.This study was undertaken to assess the antibacterial efficacy of lactobacilli isolated from curd and human milk samples. Identities of thirty-one different lactobacilli (20 from curd and 11 from human milk) were confirmed by genus-specific PCR and 16S rRNA-based sequencing. These strains belonged to five species, Lactobacillus and Bifidobacterium spp. which are extensively explored in the area of food, either as technological starters in the fermented products, as probiotics, or as potential food preservatives with a variable range of action has been shown to be successful in the management of Helicobacter pylori infection , chemical preservatives, and refrigeration are among the most preferred tools for extending the shelf-life of food items taken as control has been generously gifted by Dr. R.K. Malik, ICAR-NDRI, Karnal.de-Man Rogosa and Sharpe (MRS), Brain\u2013Heart Infusion (BHI), and Mueller\u2013Hinton agar (MHA) base were procured from Hi-Media labs, Mumbai, India. Nisin , ICAR-NDRI, Karnal, India. Two probiotic strains viz. L. rhamnosus GG and L. casei were procured from American Type Culture Collection (ATCC), USA. Ten pathogenic strains viz. B. cereus, L. monocytogenes, S. aureus, S. mutans [Gram-positive]; S. enterica serovar Typhi, E. coli, S. flexneri, P. aeruginosa, P. mirabilis, and K. pneumoniae [Gram-negative] were procured from Microbial Type Culture Collection (MTCC), Chandigarh, India. All the pathogenic strains were handled in class II, type A2 biological safety cabinet. Lactobacillus strains were maintained and propagated in MRS broth. Pathogens were maintained and propagated in BHI broth. All the bacterial cultures were preserved as glycerol stocks at \u221280\u00a0\u00b0C. Prior to the antibacterial assays, the cultures were sub-cultured thrice in their respective growth medium.Lactobacillus strains against Gram-positive and Gram-negative pathogens were determined through modified agar-well diffusion assay and used as the inoculum for performing agar-well diffusion assay , a Lactococcus lactis subsp. lactis produced natural food additive bacteriocin, was used in this study for comparative analysis. Nisaplin\u00ae at a concentration of 10,000\u00a0IU/L against B. cereus was recorded with D2, D4, and D8 closely followed by D7 and D9 (ZOI ~17\u00a0mm). Only five of the curd isolates, viz., D14, D19, D24, D25, and D26 exhibited weak activity against S. mutans. Among Gram-negative pathogens, S. enterica serovar Typhi and S. flexneri showed weak-to-moderate sensitivity toward majority of CFSs. P. mirabilis and P. aeruginosa were also inhibited by few of the lactobacilli supernatants. However, the inhibitory effect was milder. This sensitivity of Gram-negative pathogens can be linked to their thin peptidoglycan cell walls and their susceptibility toward acidic metabolites. Two of the examined strains, D14 and D29, showed mild activity against Gram-positive pathogens. In contrast, they were inactive against all the screened Gram-negative pathogens. Our findings are in agreement with those obtained by Balamurugan et al. exhibited strong inhibitory activity against B. cereus, as depicted with the high zone of inhibition among all the sensitive strains. Both B. cereus and S. enterica serovar Typhi were sensitive to the CFS of all the human milk isolates. Earlier Olivares et al. (Salmonella spp. Among the Gram-negative pathogens, all the isolates displayed weak activity against P. aeruginosa. Additionally, S. flexneri was inhibited by seven, out of eleven isolates; however, the inhibitory potential was moderate. Our findings are in accordance with Diba et al. (S. aureus and E. coli were reported to be resistant toward lactobacilli CFSs. However, sensitivity was displayed by Salmonella, Shigella, and Pseudomonas sp. Our results are also in agreement to the findings of Serrano-Nino et al. (L. monocytogenes and S. aureus.In addition, human milk lactobacilli CFSs also showed varying antagonistic patterns against the tested pathogens. Similar to curd isolates, human milk s et al. and Kozas et al. have alsa et al. , who also et al. , where hLactobacillus strains, weak-to-strong inhibitory activity was recorded against B. cereus. L. plantarum showed highest activity, with a ZOI ~20\u00a0mm. This activity can be correlated with HM-2, a human milk L. plantarum isolate showing equivalent inhibition. The pathogen inhibitory activity seems to be strain specific, since variable inhibition was recorded even within same species. Among other Gram-positive pathogens, L. monocytogenes showed resistance toward CFS of all the reference strains. S. mutans was inhibited moderately by both L. plantarum and L. brevis. Interestingly, S. aureus was sensitive toward CFS of L. rhamnosus GG and L. casei. L. brevis failed to inhibit any of the tested Gram-negative pathogens. Gram-negative pathogens, E. coli and K. pneumoniae showed resistance toward all the reference LAB strains and probiotics. Both, P. mirabilis and P. aeruginosa, were sensitive to only two, out of six reference lactobacilli CFSs. However, the activity was weak. Further, both L. rhamnosus GG and L. casei were inhibitory toward S. Typhi, S. flexneri, and P. aeruginosa. Commercially available bacteriocin, i.e., Nisin showed antagonistic activity against Gram-positive pathogens, except against S. mutans. Both S. aureus and B. cereus were inhibited to a moderate level. No inhibitory activity was observed against Gram-negative pathogens used in the study (Table\u00a0Lactobacillus CFSs may find application as bio-preservative at some point in future. Co-administration of nisin and CFSs may be explored for their synergistic additive effects, after studying their impact over sensory and nutritional attributes of food, without compromising with safety. On similar lines, Aminnezhad et al. (L. casei and L. rhamnosus against P. aeruginosa. A significant inhibitory effect of antibiotic and CFS combination over the growth of P. aeruginosa was reported.Among the six reference dy Table\u00a0. The antd et al. recentlySalmonella spp. mediated food-borne infections (Arques et al. Salmonella enterica serovar Typhi. Abdel-Daim et al. (Lactobacillus supernatants against Salmonella spp. Besides, we have also observed the antagonistic activity of Lactobacillus CFSs against P. aeruginosa, one of the alarming opportunistic pathogen in hospitalized, immuno-compromised, and cystic fibrosis patients. P. aeruginosa-mediated infections are often life-threatening and complicated to treat, due to limited susceptibility to commonly practiced antimicrobial drugs (Jamalifar et al. P. aeruginosa.Dairy products along with meat and eggs are the most common causes of m et al. and Bahrm et al. also repLactobacillus isolates exhibited pathogen inhibitory activity comparable to the probiotic strains. Overall, CFSs of all the tested lactobacilli exhibited strong-to-moderate antagonistic activity against B. cereus, which causes severe food poisoning and is frequently isolated from uncooked and unprocessed products such as rice, condiments, vegetables, meat, and milk products. This highly toxic strain is reported to be responsible for food-related fatalities (Arnesen et al. Lactobacillus strains, such as inhibition of cancer metastasis, positive modulation of the intestinal immune response, and cholesterol-lowering properties (Arena et al. Few of the CFSs of curd and human milk"} +{"text": "Scientific Reports6: Article number: 3156310.1038/srep31563; published online: 08192016; updated: 10052016The original version of this Article contained a typographical error in the spelling of the author Jo\u00eblle Cohen-Tannoudji, which was incorrectly given as Joelle-Cohen-Tannoudji.The Author Contributions statement,\u201cJ.L. and B.Q. conceived and designed the experiments. J.L., D.L., A.F.-V., G.G. and J.-N.L. performed the experiments. J.L., J.-C.-T. and B.Q. analysed the data and wrote the paper. All authors discussed the results and reviewed the manuscript\u201d.now reads:\u201cJ.L. and B.Q. conceived and designed the experiments. J.L., D.L., A.F.-V., G.G. and J.-N.L. performed the experiments. J.L., J.C.-T. and B.Q. analysed the data and wrote the paper. All authors discussed the results and reviewed the manuscript\u201d.These errors have now been corrected in the PDF and HTML versions of the Article."} +{"text": "Scientific Reports 10.1038/s41598-017-09482-w, published online 18 August 2017Correction to: The original version of this Article contained typographical errors in the spelling of the authors \u201cKarolina Mikulska-Ruminska, Andrej J. Kulik, Carine Benadiba, Ivet Bahar, Giovanni Dietler & Wieslaw Nowak\u201d which were incorrectly given as \u201cK. Mikulska-Ruminska, A. J. Kulik, C. Benadiba, I. Bahar, G. Dietler & W. Nowak\u201d. This has now been corrected in the PDF and HTML versions of the Article, and in the Supplementary Information file."} +{"text": "To examine hepatitis B (HBV) serological markers and plasma DNA concentrations in a large group of untreated HBV/HIV-coinfected individuals in two sub-Saharan settings.Baseline analysis of a randomized controlled trial.n\u200a=\u200a2317) and Harare, Zimbabwe (n\u200a=\u200a999). HBV serological markers and plasma HBV DNA viral load were measured retrospectively on stored baseline samples. Logistic regression was used to examine associations with baseline demographic and clinical factors.DART was a large trial of treatment monitoring practices in HIV-infected adults with advanced disease starting antiretroviral therapy at centres in Kampala or Entebbe, Uganda (P\u200a<\u200a0.001) despite a similar prevalence of antibody to HBV core antigen (56.3 vs. 52.4%) in the two settings. Overall, HBsAg positivity was associated with male sex but not with age, WHO disease stage, or CD4+ cell count. HBeAg was detected among 37% of HBsAg-positive patients, with higher rates among those with advanced WHO stage (P\u200a=\u200a0.02). Also in HBsAg-positive patients, HBV DNA was undetectable in 21%, detectable but below the level of quantification in 14%, and quantifiable in 65%. A total of 96% of HBeAg-positive and 70% of HBeAg-negative patients had detectable HBV DNA; 92 and 28% of patients, respectively, had HBV DNA viral load more than 2000\u200aIU/ml.The rate of HBsAg positivity was significantly higher in Zimbabwe than Uganda (12.2 vs. 7.7%, adjusted odds ratio\u200a=\u200a1.54, High rates of HBV coinfection were observed, highlighting the importance of ensuring that coinfected patients receive an antiretroviral regimen, whether first-line or not, that is active against both viruses. In the era of antiretroviral treatment (ART), death rates from AIDS-related causes have declined dramatically in both resource-limited and resource-rich regions. In this context, liver disease has emerged as a major cause of death in HIV-infected individuals, although the absolute rates of liver-related mortality have declined \u20133. LiverWHO HIV treatment guidelines state that it is important to determine the local prevalence of hepatitis B (HBV) to inform the decision whether to screen individuals for viral hepatitis, as recommended in resource-rich countries . The useWe measured a comprehensive set of HBV serological markers and plasma HBV DNA viral load in archived baseline samples from over 3000 HIV-infected participants in the DART trial. This has allowed a detailed characterization of HBV/HIV coinfection in the regions from where participants were recruited, namely, Kampala/Entebbe, Uganda and Harare, Zimbabwe.+ and haematological/biochemical toxicity tests. Results were not returned for patients in the CDM arm unless specifically requested by the patient's doctor or if a grade 4 toxicity occurred. All participants started first-line ART with zidovudine and lamivudine and either tenofovir, nevirapine, or abacavir. Inclusion criteria were: age at least 18 years, CD4+ cell count less than 200 cells/\u03bcl, and naive to ART except for exposure for the prevention of mother-to-child transmission. Exclusion criteria were: likely to be unable to attend follow-up, likely to have poor compliance, acute infection including intense phase of tuberculosis treatment, malignancy requiring chemotherapy, laboratory test result indicative of contraindication to ART , pregnancy, and breastfeeding and Zimbabwe . Patients were randomized to clinically driven monitoring only (CDM) or clinical monitoring and routine laboratory monitoring in the form of 12-weekly CD4tfeeding .Plasma samples were stored at screening, enrolment, and each scheduled 3-monthly clinic visit. The current study describes the results of serological and virological tests for HBV that were performed retrospectively on the screening or enrolment sample for all participants, according to the algorithm in Fig. 6\u200aIU/ml), whereas Harare used Abbott RealTime HBV after manually preparing samples using the mSample Preparation SystemDNA . Due to low sample volumes, all samples at JCRC were diluted 1\u200a:\u200a4, giving a quantitative range of 48\u2013440\u200a\u00d7\u200a106\u200aIU/ml. Both JCRC and Harare participated in the United Kingdom National External Quality Assessment Service (UKNEQAS) scheme. Results from the three Uganda sites were broadly similar and have been combined in the analysis.Serological and HBV DNA viral load assays were conducted locally, except for the testing of HBeAg, anti-HBe, and HBV DNA on UVRI samples, which were transported to and tested at JCRC. All sites used commercial serological assays . The HBsAg assays were known to be unaffected by recognized HBsAg mutants; positive results were confirmed by a neutralization test. Anti-HBs results were classified as positive if the concentration was more than 10\u200amIU/ml. For the quantification of HBV DNA, JCRC used Roche Cobas Ampliprep/Cobas TaqMan are presented from models fitting each variable as a continuous factor. Pairwise interactions between baseline factors were assessed by adding these to the model individually in addition to the main effects; in view of the large number of interaction terms examined, only those significant at P value less than 0.01 are reported.Multivariable logistic regression was used to examine associations between baseline factors and anti-HBc, HBsAg, HBeAg status, and HBV DNA viral load concentration . P vP\u200a<\u200a0.001). Reflecting the inclusion criteria, the population had advanced infection; median CD4+ cell count was 86 cells/\u03bcl, and 23% had previously been diagnosed with a WHO stage 4 illness.Selected baseline characteristics of the DART population are shown in Table P\u200a=\u200a0.005, test for interaction). No association was observed with WHO stage or baseline CD4+ cell count.Data completeness was excellent, with only five (0.2%) participants not tested for anti-HBc and one (0.04%) not tested for HBsAg. The rate of anti-HBc positivity was similar in participants from the sites in Uganda (52%) and Zimbabwe (56%). Men were significantly more likely to test positive than women , although this difference was more marked in Zimbabwe than Uganda (n\u200a=\u200a31) of them had other evidence of HBV infection in the form of detectable HBeAg, anti-HBe, or HBV DNA. A significantly higher rate (P\u200a=\u200a0.001) of anti-HBc-negativity was observed in Zimbabwe than in Uganda , and evidence of a higher rate at lower ages . No associations were observed for the other variables examined .A total of 308 (9%) patients were found to be HBsAg-positive, 54 (18%) of whom were anti-HBc-negative, although most were anti-HBs-positive, consistent with a resolved infection and natural immunity.In contrast to the similar rates of anti-HBc positivity, HBsAg was detected much more frequently in Zimbabwean patients (17%) than in Ugandan patients (6%). HBsAg positivity was significantly higher in men but there was no association with age, WHO stage, or CD4P\u200a=\u200a0.10) (Table P\u200a=\u200a0.02) and CD4+ cell count (P\u200a=\u200a0.09).A total of 280 (91%) patients who were HBsAg-positive had sufficient sample to allow further testing for HBeAg and anti-HBe. A total of 103 (37%) were HBeAg-positive and 127 (45%) were anti-HBe-positive; six (2%) patients had dual positive results and 56 (20%) dual negative results. HBeAg positivity was not associated with country or age, although there was a trend towards a higher prevalence in men (44%) than in women (31%) .Of 308 patients with a positive HBsAg result, 270 (88%) with available samples were tested for HBV DNA viral load. A total of 56 (21%) had undetectable DNA, 38 (14%) had DNA detectable but below the level of quantification, and 176 (65%) had a quantifiable level of DNA. The detection of HBV DNA viral load was strongly linked to HBeAg status, 96% (80/83) of HBeAg-positive and 70% (117/167) of HBeAg-negative participants having detectable levels to have an HBV DNA level above this threshold, largely driven by differences among HBeAg-negative patients. The only other significant factor was WHO stage (in the model that did not adjust for HBeAg status), with a higher probability of having HBV DNA viral load more than 2000\u200aIU/ml the more advanced the stage (P\u200a=\u200a0.03).Table et al.[+ cell count, sometimes with development of an anti-HBc response on starting ART [The description of the seroepidemiology of hepatitis B in HIV-infected adults in sub-Saharan Africa is largely limited to HBsAg and anti-HBc. In a systematic review of these markers, Barth et al. reportedet al.\u201325. Notaet al.,26, and et al.. In HIV-ting ART . As an ating ART .A total of 543 participants, 30.0% of those with evidence of HBV exposure, had isolated anti-HBc. Similar rates 32\u201342%) have been found in previous studies in Uganda and elsewhere in sub-Saharan Africa \u201342% have. This pan\u200a=\u200a115) in which at least 28% of HBeAg-negative participants had HBV DNA greater than 2000\u200aIU/ml [The major novel contribution from our study in an HIV-positive population in Africa is extensive data on HBeAg and HBV DNA viral load, the most powerful prognostic markers for disease progression and viral transmission. Previous studies are either based on small sample sizes or do not distinguish HIV-uninfected and HBV/HIV-coinfected individuals. A previous study of mostly HIV-negative, HBsAg-seropositive inpatients in Kampala found 27% HBeAg seropositive . An earl00\u200aIU/ml . Among H+ cell count at study entry. No clear associations were observed for HBsAg status, but HBeAg positivity was markedly higher in those with a more advanced WHO stage of disease, and there was a consistent, albeit nonsignificant, trend with CD4+ cell count. The effect of WHO stage was mirrored in an analysis of the proportion of participants with HBV DNA levels greater than 2000\u200aIU/ml. Reactivation of HBV infection could explain the higher liver-related mortality that has been observed in HBV/HIV-coinfected individuals [+ cell count) and both HBeAg and HBsAg status was noted previously in a study in Nigeria, although these investigators suggested causation to be acting in the other direction, namely, active HBV infection lowering CD4+ cell count [Immunosuppression associated with HIV coinfection can result in reactivation of HBV infection, with reappearance of HBsAg or HBeAg, or a reduction in the rate of loss of either marker over time. Without an HIV-negative comparator population, we were not able to examine this; however, we were able to assess the influence of the degree of immunosuppression as measured by WHO clinical stage and CD4ll count .The prevalence of anti-HBc was significantly higher in male participants than in female participants, particularly in Zimbabwe. An even more pronounced sex difference was observed for HBsAg, consistent with other studies that have shown that men are less likely to clear HBV and progress to chronic infection, either when infected in childhood or as adults \u201342. Thern\u200a=\u200a543) who had isolated anti-HBc. This serological pattern may represent a false-positive, resolved and cleared infection, or chronic infection with a low rate of viral replication (occult HBV infection). In a previous small study in Uganda, 15% (seven of 48) HIV-positive patients with negative HBsAg had detectable HBV DNA [+ cell count less than 200 cells/\u03bcl and thus did not include those with less-advanced HIV infection. This may have limited our ability to identify associations with this key marker of immunosuppression.The strengths of our study are the large sample size, the very high rate of sample retrieval (close to 100%), detailed clinical and demographic data, the comprehensive range of virological markers tested, and that all the laboratories were participating in the UKNEQAS quality assurance programme. The main limitation is the testing of participants at a single time point, precluding the estimation of HBV incidence and the ability to determine with certainty that all the HBsAg positivity was due to chronic HBV infection or whether there may have been some acute infections that may resolve. It is unlikely that acute infection contributes substantially to HBsAg prevalence as most transmission in sub-Saharan Africa occurs in childhood. Another limitation is that we did not perform HBV DNA assays on the surprisingly large number of patients , the UK Department for International Development (DFID), and the Rockefeller Foundation. GlaxoSmithKline/ViiV Healthcare, Gilead, Boehringer Ingelheim, and AbbVie Inc. donated drugs for DART. Gilead Sciences funded the HBV immunological and virological assays. H.P. was funded by a UK Medical Research Council Clinical Research Training Fellowship.Authors\u2019 contributions: H.P. \u2013 designed and coordinated study, carried out analysis, wrote first draft, and revised subsequent versions; D.D. \u2013 designed and coordinated study, advised on analysis, cowrote first draft, and revised subsequent versions; T.Z. and T.V. \u2013 carried out laboratory testing, commented on drafts; M.C. \u2013 carried out laboratory testing; C.K., P.M., and J.H. \u2013 site PI for main trial, commented on drafts; M.S. \u2013 coordinated study, commented on drafts; C.G. and D.P. \u2013 designed study, commented on drafts; P.K. \u2013 commented on drafts; R.G. \u2013 designed and coordinated study, commented on drafts.Justification of the number of contributors greater than 10: DART was a very large international study with a large study group.DART Virology Group: P. Kaleebu (Co-Chair), D. Pillay (Co-Chair), P. Awio, M. Chirara\u2217, D. Dunn, D.M. Gibb, C. Gilks, R. Goodall, A. Kapaata, M. Katuramur, F. Lyagoba, B. Magambo, K. Mataruka, L. Mugarura, T. Musunga, M. Nabankkema, J. Nkalubo, P. Nkurunziza, C. Parry, V. Robertson, M. Spyer, D. Mulima, D.E. Williams, I. Nankya, S. Nassimbwa, E. Ndashimye, E. Nabulime, M. Phiri, K. Mutasa, and S. Mukasa. MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda: H. Grosskurth, P. Munderi, G. Kabuye, D. Nsibambi, R. Kasirye, E. Zalwango, M. Nakazibwe, B. Kikaire, G. Nassuna, R. Massa, K. Fadhiru, M. Namyalo, A. Zalwango, L. Generous, P. Khauka, N. Rutikarayo, W. Nakahima, A. Mugisha, J. Todd, J. Levin, S. Muyingo, A. Ruberantwari, P. Kaleebu, D. Yirrell, N. Ndembi, F. Lyagoba, P. Hughes, M. Aber, A. Medina Lara, S. Foster, J. Amurwon, and B. Nyanzi Wakholi.Joint Clinical Research Centre, Kampala, Uganda: P. Mugyenyi, C. Kityo, F. Ssali, D. Tumukunde, T. Otim, J. Kabanda, H. Musana, J. Akao, H. Kyomugisha, A. Byamukama, J. Sabiiti, J. Komugyena, P. Wavamunno, S. Mukiibi, A. Drasiku, R. Byaruhanga, O. Labeja, P. Katundu, S. Tugume, P. Awio, A. Namazzi, G.T. Bakeinyaga, H. Katabira, D. Abaine, J. Tukamushaba, W. Anywar, W. Ojiambo, E. Angweng, S. Murungi, W. Haguma, S. Atwiine, and J. Kigozi.University of Zimbabwe, Harare, Zimbabwe: A. Latif, J. Hakim, V. Robertson, A. Reid, E. Chidziva, R. Bulaya-Tembo, G. Musoro, F. Taziwa, C. Chimbetete, L. Chakonza, A. Mawora, C. Muvirimi, G. Tinago, P. Svovanapasis, M. Simango, O. Chirema, J. Machingura, S. Mutsai, M. Phiri, T. Bafana, M. Chirara, L. Muchabaiwa, and M. Muzambi.Infectious Diseases Institute (formerly the Academic Alliance) Makerere University, Mulago, Uganda: E. Katabira, A. Ronald, A. Kambungu, F. Lutwama, A. Nanfuka, J. Walusimbi, E. Nabankema, R. Nalumenya, T. Namuli, R. Kulume, I. Namata, L. Nyachwo, A. Florence, A. Kusiima, E. Lubwama, R. Nairuba, F. Oketta, E. Buluma, R. Waita, H. Ojiambo, F. Sadik, J. Wanyama, and P. Nabongo.The AIDS Support Organisation (TASO), Uganda: R. Ochai and D. Muhweezi.Imperial College, London, UK: C. Gilks, K. Boocock, C. Puddephatt, D. Winogron, and J. Bohannon.MRC Clinical Trials Unit at UCL, London, UK: J. Darbyshire, D.M. Gibb, A. Burke, D. Bray, A. Babiker, A.S. Walker, H. Wilkes, M. Rauchenberger, S. Sheehan, L. Peto, K. Taylor, M. Spyer, A. Ferrier, B. Naidoo, D. Dunn, and R. Goodall.Independent DART Trial Monitors: R. Nanfuka and C. Mufuka-Kapuya.Trial Steering Committee: I. Weller (Chair), A. Babiker , S. Bahendeka, M. Bassett, A. Chogo Wapakhabulo, J. Darbyshire, B. Gazzard, C. Gilks, H. Grosskurth, J. Hakim, A. Latif, C. Mapuchere, O. Mugurungi, P. Mugyenyi; Observers: C. Burke, M. Distel, S. Jones, E. Loeliger, P. Naidoo, C. Newland, G. Pearce, S. Rahim, J. Rooney, M. Smith, W. Snowden, J.-M. Steens, and M. Ait-Khaled.Data and Safety Monitoring Committee: A. Breckenridge (Chair), A. McLaren (Chair-deceased), C. Hill, J. Matenga, A. Pozniak, and D. Serwadda.Endpoint Review Committee: T. Peto (Chair), A. Palfreeman, M. Borok, and E. Katabira.There are no conflicts of interest."} +{"text": "Yet understanding how this tissue and whole organism moderates energy turnover is hampered by a lack of information regarding how relevant enzymes differ in sequence, expression, and regulation.Hummingbirds oxidize ingested nectar sugars directly to fuel foraging but cannot sustain this fuel use during fasting periods, such as during the night or during long-distance migratory flights. Instead, fasting hummingbirds switch to oxidizing stored lipids that are derived from ingested sugars. The hummingbird liver plays a key role in moderating energy homeostasis and this remarkable capacity for fuel switching. Additionally, liver is the principle location of de novo transcriptome of the hummingbird liver using PacBio full-length cDNA sequencing (Iso-Seq), yielding 8.6Gb of sequencing data, or 2.6M reads from 4 different size fractions. We analyzed data using the SMRTAnalysis v3.1 Iso-Seq pipeline, then clustered isoforms into gene families to generate de novo gene contigs using Cogent. We performed orthology analysis to identify closely related sequences between our transcriptome and other avian and human gene sets. Finally, we closely examined homology of critical lipid metabolism genes between our transcriptome data and avian and human genomes.We generated a We confirmed high levels of sequence divergence within hummingbird lipogenic enzymes, suggesting a high probability of adaptive divergent function in the hepatic lipogenic pathways. Our results leverage cutting-edge technology and a novel bioinformatics pipeline to provide a first direct look at the transcriptome of this incredible organism. Archilochus colubris), achieve some of the highest mass-specific metabolic rates observed among vertebrates .Supplemental data 1. Alignments of amino acid sequence for hepatic lipogenic enzymes for compared species .Supplemental data 2. Alignments of coding sequence for hepatic lipogenic enzymes for compared species [canna = K.C.W, W.T., and G.W.W. conceived and designed the study. A.M.M. performed specimen sacrifice and extracted nucleic acid for sequencing. R.E.W. performed sequencing library preparation. R.E.W., A.M.M., E.T. and W.T. implemented the data analyses. R.E.W., A.M.M., G.W.W., K.C.W., W.T., interpreted the results and wrote the manuscript.ASD: all sequence data; BUSCO: benchmarking universal single-copy ortholog; CCD: Cogent collapsed data; CCS: chimeric circular consensus; CCS: chimeric circular consensus; CDS: coding sequence; GLUT: glucose transporter; GO: gene ontology; HQD: high-quality data; ORF: open reading frame; PCR: polymerase chain reaction; UCP: uncoupling protein.W.T. and R.W. have received travel funds to speak at symposia organized by Pacific Biosciences. Bulk of reagents for IsoSeq were provided by Pacific Biosciences.GIGA-D-17-00088_Original_Submission.pdfClick here for additional data file.GIGA-D-17-00088_Revision_1.pdfClick here for additional data file.GIGA-D-17-00088_Revision_2.pdfClick here for additional data file.GIGA-D-17-00088_Revision_3.pdfClick here for additional data file.Response_to_Reviewer_Comments_Original_Submission.pdfClick here for additional data file.Response_to_Reviewer_Comments_Revision_1.pdfClick here for additional data file.Response_to_Reviewer_Comments_Revision_2.pdfClick here for additional data file.Reviewer_1__(Attachment).pdfClick here for additional data file.Reviewer_1_Report_ -- Sandeep Chakraborty02 May 2017 ReviewedClick here for additional data file.Reviewer_1_Report_(Revision_1) -- Sandeep Chakraborty03 Nov 2017 ReviewedClick here for additional data file.Reviewer_2_Report_ -- Robert Ekblom23 May 2017 ReviewedClick here for additional data file.Reviewer_2_Report_(Revision_1) -- Robert Ekblom20 Oct 2017 ReviewedClick here for additional data file.Supplemental materialClick here for additional data file."} +{"text": "Nature Communications7 Article number: 11208 ; DOI: 10.1038/ncomms11208 (2016) Published 04072016; Updated 07282017This Article contains an error in the author contributions section that has resulted in incorrect credit for preparation and critical analysis of the manuscript. The correct author contributions section is as follows:\u2018T.M. designed, analysed, performed and interpreted most experiments and wrote the paper. A.L.E. performed and analysed experiments. L.V. and Y.Y. performed and interpreted bioinformatics analyses pertaining to the genomic characterization of the MKs. M.R.T. contributed to megakaryocyte characterization and wrote the paper. M.W.T. performed and interpreted bioinformatics analyses pertaining to the forward programming concept. M.C. and M.A. contributed to megakaryocyte characterization. D.H., W.H.W., C.M.H., A.D., R.L., G.B. and D.C.P. performed experiments. H.P., T.P. and A.B. designed and performed intravital experiments and analysed data, A.B. also participated in preparation and critical analysis of the manuscript. N.S. interpreted bioinformatics analyses pertaining to the genomic characterization of the MKs. W.H.O. contributed platelet expert input to the forward programming concept. R.A.P. conceived the forward programming approach, designed, analysed and interpreted experiments and wrote the paper. C.G. drove the platelet biology, designed, analysed and interpreted experiments and wrote the paper.\u2019"} +{"text": "Panel A) and sagittal (Panel B) views. This CT abnormality raised the suspicion of left atrial thrombus or tumour, prompting further cardiac imaging.A 52-year-old woman with atopic asthma and a long smoking habit underwent CT pulmonary angiography (CTPA) for investigation of atypical, pleuritic chest pain. There was no history of heart disease or cardiovascular risk factors. As per usual practice for non-cardiac imaging, CTPA was performed without ECG gating. While there was no pulmonary embolism, CT showed an apparent large left atrial filling defect (arrows), demonstrated in axial and four-chamber views, showed the left atria to be of normal size and devoid of any visible mass. There was, however, an atrial septum aneurysm, which exhibited 2 cm shift from midline (arrows). Bi-ventricular size and function were normal, and there was no intra-atrial shunt seen on colour Doppler. No medical or surgical intervention was required for this incidental radiographic finding.Transoesophageal echocardiography, shown in short-axis .J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). J.H.F.R. is part supported by HEFCE. M.R.B. and J.H.F.R are supported by the NIHR Cambridge Biomedical Research Centre and the British Heart Foundation.European Heart Journal\u2014 Cardiovascular Imaging online.Supplementary data are available at"} +{"text": "Rosing, Z. Zhang, L. Hughes, V. Kansra, M. Sanghvi, M. M. Tibben, A. Gebretensae, J. H. M. Schellens and J. H. Beijnen, was originally published electronically on the publisher\u2019s internet portal (currently SpringerLink) on 17th October 2017 without open access.The article \u201cDetermination of the absolute oral bioavailability of niraparib by simultaneous administration of a http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The original article was corrected.With the author(s)\u2019 decision to opt for Open Choice the copyright of the article changed on 24th November to _ The Author(s) 2017 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ("} +{"text": "Scientific Reports7:5560; doi:10.1038/s41598-017-05149-8; Article published online 17 July 2017P. F. Weck was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article.The Acknowledgements section now reads:The authors would like to thank the staffs at the BARC-TIFR Pelletron accelerator facility for smooth operation of the machine. We thank D. Misra for his various helps during the measurements. P.F.W would like to thank the Sandia National Laboratories which is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy\u2019s National Nuclear Security Administration under Contract DE-NA0003525.The Author Contributions section now reads:L.C.T. had the idea and planned this experiment. L.C.T. and S.B. executed the experiment, analysis and interpretation. C.C. and P.F.W. provided the model calculations in which P.F.W. provided the wave functions of the molecules whereas C.C. contributed towards the CB1 model calculations. L.C.T.,S.B. and C.C. prepared the paper which was reviewed by all the authors."} +{"text": "Acta Cryst. (2006), E62, m983\u2013m985.Erratum to et al. , the metal atom was reported incorrectly.In the paper by Zhu"} +{"text": "During 2007\u20132012, use of opioid analgesics in the United States decreased with increasing income; 8.9% of adults aged \u226520 years who had family incomes <200% of the federal poverty threshold used an opioid analgesic in the preceding 30 days, compared with 7.1% of those with incomes 200%\u2013399% of the poverty threshold and 4.9% of those with incomes \u2265400% of the poverty threshold. The relationship between income and opioid use was observed for both men and women. Within each of the family income categories, there were no significant differences in opioid analgesic use between men and women.Source: Frenk SM, Porter KS, Paulozzi LJ. Prescription opioid analgesic use among adults: United States, 1999\u20132012. NCHS data brief no. 189; 2015. Available at http://www.cdc.gov/nchs/data/databriefs/db189.htm.Reported by: Steven M. Frenk, PhD, sfrenk@cdc.gov, 301-458-4096; Kathryn S. Porter, MD, Leonard J. Paulozzi, M.D."} +{"text": "In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a nonfasting state for the greater part of the day, and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were identified with significant changes after the meal, for which 38 gene-metabolite associations were analyzed. Of these 38 associations, 31 gene-metabolite associations were replicated with postprandial metabolite concentrations. These data indicate that the genetics of fasting and postprandial metabolite levels are significantly overlapping. In 2015, a genome-wide association study described 59 independent signals that showed strong associations with a wide range of metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit derived from protein, 50 En% carbohydrates, and 34 En% fat] was consumed, and subsequent blood samples were drawn 150 min after the meal. Metabolomic measurements were performed in the postprandial EDTA-plasma samples with the Biocrates AbsoluteIDQ p150 assay. The metabolite concentrations were logarithm-transformed to obtain normal distributions.2] the metabolite concentrations were measured 150 min after a mixed meal.This study was embedded in the Netherlands Epidemiology of Obesity (NEO) study, a population-based prospective cohort with 6,671 participants from the greater area of Leiden (in the west of the Netherlands) . In 478 Candidate single nucleotide polymorphisms (SNPs).We set out to examine 123 genetic associations with fasting metabolites reported in Draisma et.al (t-tests to identify the metabolites with significant changes (P < 0.05) after the meal. Additive genetic models were used to assess the associations to the postprandial metabolite concentrations by linear regressions, adjusted for age, sex, BMI, and the first four principal components. A P value<1.3E-3 was considered as a successful replication.We used paired n = 19) previously identified based on fasting metabolites also revealed pronounced associations to postprandial metabolites. For some gene-metabolite associations the effect size was much larger for the postprandial concentration than for the fasting concentration, e.g., rs1171614 with acetyl-L-carnitine (C2) and rs2238732 with proline .Of the 54 postprandial metabolites, 23 changed significantly in concentration after the meal, involving 38 gene-metabolite associations. Half of these 38 associations (In this study, we replicated half of the previously described gene fasting-metabolite associations in postprandial metabolites after a mixed meal with very high levels of significance. Interestingly, some of the genetic signals were stronger as compared with fasting metabolite concentrations.Metabolite measurements were performed with support of the Dutch Science Foundation ZonMW - VENI Grant 916.14.023.No conflicts of interest, financial or otherwise, are declared by the authors.R.L.-G. and D.O.M.K. analyzed data; R.L.-G. and D.O.M.K. interpreted results of experiments; R.L.-G. prepared figures; R.L.-G. drafted manuscript; R.L.-G., R.d.M., K.W.v.D., and D.O.M.K. edited and revised manuscript; R.L.-G., R.d.M., F.R.R., K.W.v.D., and D.O.M.K. approved final version of manuscript; R.d.M., F.R.R., and K.W.v.D. conceived and designed research."} +{"text": "R. Soc. open. sci.4, 170261. (Published 12 July 2017). (doi:10.1098/rsos.170261)The Authors' contributions section in the published paper is incorrect. The correct authors' contributions are as follows:K.P.A. conceived and designed the project and interpreted the results. G.G. prepared the samples for the study, conceived and designed the approach, analysed the data, interpreted the results and wrote the manuscript. S.K., A.T. and S.M.Ch.S. analysed the data and interpreted the results. K.P.A., S.K., A.T. and S.M.Ch.S. contributed in writing and improving the manuscript. All authors have read and approved the final version."} +{"text": "Acta Cryst. (2007), E63, m2664.Erratum to et al. , the metal atom was reported incorrectly.In the paper by Wu"} +{"text": "AbstractDichodon (Bartl. ex Rchb.) Rchb. was previously reinstated based on results from recent molecular phylogenetic studies. Accordingly, Dichodonparvipetalum (Hosok.) G. Yao, a new combination for the species Cerastiumparvipetalum Hosok. is proposed.The generic name Cerastium L. in the broad sense consists of nearly 100 species mainly distributed in temperate and cold regions, with 23 species occurring in China and Dichodon (Bartl. ex Rchb.) Boiss. Rchb. in their comprehensive taxonomic study of Caryophyllales. In the Flora of China, two species (viz. Cerastiumcerastoides (L.) Britton and Cerastiumparvipetalum Hosok.) belonging to the subgenusDichodon were accepted (Dichodon (Dichodoncerastoides (L.) Rchb.) by Dichodon. Accordingly, the new combination Dichodonparvipetalum is proposed below.The genus in China . Traditie teeth) . In a ree teeth) , the subaccepted . The forTaxon classificationPlantaeCaryophyllalesCaryophyllaceae(Hosok.) G. Yaocomb. nov.urn:lsid:ipni.org:names:60473146-2Cerastiumparvipetalum Hosok., Trans. Nat. Hist. Soc. Taiwan 22: 227. 1932. TYPE: CHINA. Taiwan, Kaohsiung, 3 Jan. 1931, T. Hosokawa 93"} +{"text": "While not members of the Board of Editors, invited editors serve an important role in the review process. Invited editors are experts in their fields of research who add an additional level of quality to the review process. An editor may assign a paper to an invited editor when he/she would like to have an additional expert opinion of the reviews or when the subject area falls outside the editor\u2019s primary area of expertise.On behalf of the editors of The time and effort of the following experts in handling articles have been essential to ensuring the high quality of our publications, and their help is greatly appreciated.Rama Rao AmaraDaniel BarberStephen J. BarenkampRalph S. BaricMichael P. BarrettDennis A. BazylinskiMarcel A. BehrStephen M. BeverleyDavid C. BloomElhanan BorensteinRomain BriandetRoland BroschC. Titus BrownDennis R. BurtonMark J. ButtnerAmbrose CheungEric A. CohenAlan CollmerLaurie E. ComstockCarolyn B. CoyneBlossom DamaniaRobert DaumEdward F. DeLongSarah E. F. D\u2019OrazioPieter C. DorresteinAdam DriksLuis EnjuanesPaul D. FeyKevin FosterEric O. FreedClay FuquaLee GehrkeMichael GillingsGustavo H. GoldmanAndrew GoodmanAnn GriffenChristoph GrundnerDavid L. GutnickAnders P. HakanssonJ. Marie HardwickRonald N. HartyDavid E. HeinrichsJeffrey P. HendersonAlexander R. HorswillKelly T. HughesGregory B. HurstJoseph M. HyserAkiko IwasakiBabak JavidJorgen JohanssonPaul D. R. JohnsonYoshihiro KawaokaDan KnightsDavid M. KnipeArash KomeiliAnna KonovalovaNatacha KremerNathaniel Roy LandauJean-Paul LatgeBen-hur LeeJean Claire LeeStuart M. LevitzJaisri R. LingappaPeter N. LipkeGeorge LiuHaoping LiuMelissa Bruckner LodoenJeremy LubanRebecca Marie LynchRyszard MaleszkaAnthony W. MaressoJose L. MartinezDenise MonackCesare MontecuccoDavid C. MontefioriLynda A. MorrisonJames M. MusserDavid D. MyroldMichael Noel NeelyStuart J. NeilHiroshi NikaidoVictor NizetHimadri B. PakrasiKelli L. PalmerPyong ParkJohn ParkinsonEverett PesciDavid A. RaskoJyothi RengarajanFederico ReyAnthony R. RichardsonD. Ashley RobinsonForest RohwerEugene RosenbergIlan RosenshinePhilip C. RosenstielCraig R. RoyTracy RuckwardtNatividad RuizPeter SarnowHerbert P. SchweizerGanes C. SenJoshua ShaevitzM. Sloan SiegristThomas J. SilhavyDavid SkurnikJustin SonnenburgMichael N. StarnbachFrank StewartGisela StorzPaul D. StraightGurol SuelSue A. TolinAna TravenSusannah Green TringeMeera UnnikrishnanSusana T. ValenteJesus ValenzuelaMarjan W. van der WoudeJorge Eugenio VidalAlan W. WalkerMark J. WalkerDigby F. WarnerScott C. WeaverMalcolm WhitewaySteven S. WitkinAlan J. Wolfe"} +{"text": "Scientific Reports7: Article number: 4169910.1038/srep41699; published online: 02092017; updated: 02122018The Acknowledgements section in this Article is incomplete.\u201cF.D.A. and C.M.B.M. acknowledge the support of FCT, under contracts SFRH/BPD/74775/2010 and SFRH/BPD/76842/2011, respectively. We acknowledge R. Ferreira (UCQfarma), J. Catita and J. Carvalheira , for their assistance with the particle size distribution measurement. The measurements were performed at the Swiss Spallation Neutron Source SINQ at the Paul Scherrer Institute. We acknowledge C. Schanzer of the SwissNeutronics AG and M. Horisberger for access to the neutron beam.\u201dshould read:\u201cF.D.A. and C.M.B.M. acknowledge the support of FCT, under contracts SFRH/BPD/74775/2010 and SFRH/BPD/76842/2011, respectively. We acknowledge R. Ferreira (UCQfarma), J. Catita and J. Carvalheira , for their assistance with the particle size distribution measurement. The measurements were performed at the Swiss Spallation Neutron Source SINQ at the Paul Scherrer Institute. We acknowledge C. Schanzer of the SwissNeutronics AG and M. Horisberger for access to the neutron beam. This work is financed by national funds thru FCT \u2013 Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P., in the framework of project UID/FIS/04559/2013.\u201d"} +{"text": "Scientific Reports 10.1038/s41598-017-15407-4, published online 08 November 2017Correction to: The Acknowledgements section in this Article is incomplete.\u201cThis work was supported by US National Institutes of Health awards R21 CA204563 to D.J.S and R21 CA199631 and K12 CA138464 to L.G.C.C., and by the V Foundation from Cancer Research to L.G.C.C.\u201dshould read:\u201cThis work was supported by US National Institutes of Health awards R21 CA204563 to D.J.S and R21 CA199631 and K12 CA138464 to L.G.C.C., and by the V Foundation from Cancer Research to L.G.C.C. N.B.C. was supported by US National Institutes of Health Training Grant T32 GM007377.\u201d"} +{"text": "Nature Communications 10.1038/s41467-017-01893-7; Article published online: 28 November 2017Correction to: The original HTML version of this Article omitted to list Yeshayahu Lifshitz as a corresponding author and incorrectly listed Shuit-Tong Lee as a corresponding author.Correspondingly, the original PDF version of this Article incorrectly stated that \u201cCorrespondence and requests for materials should be addressed to X.J. (email: xin.jiang@uni-siegen.de), or to Y.L. (email: yangl@suda.edu.cn), or to S.-T.L. (email: shayli@technion.ac.il), or to Z.K. (email: zhkang@suda.edu.cn)\u201d, instead of the correct \u201cCorrespondence and requests for materials should be addressed to X.J. (email: xin.jiang@uni-siegen.de), or to Y. Liu (email: yangl@suda.edu.cn), or to Y. Lifshitz (email: shayli@technion.ac.il), or to Z.K. (email: zhkang@suda.edu.cn)\u201d.This has now been corrected in the PDF and HTML versions of the Article."} +{"text": "AbstractPseudobombax are presented. One new combination and two new heterotypic synonyms for taxa originally described from Brazil and Ecuador are proposed based on both morphological and previously published molecular evidence. The taxonomic changes will be adopted in a treatment of Pseudobombax for the upcoming Brazilian Flora 2020 and in a forthcoming revision of the genus throughout its range.Taxonomic notes in the Neotropical genus Pseudobombax Dugand along with previously published molecular phylogenetic studies , which is being prepared for the upcoming Brazilian Flora 2020 (http://floradobrasil.jbrj.gov.br/). The changes also will be incorporated in a taxonomic revision of the genus throughout its range.Field and herbarium studies of the Neotropical genus studies revealedPageBreakPseudobombax was evaluated in order to check typifications and synonymies of taxa. Information about type specimens was derived from protologues and checked against major online nomenclatural indices . Herbarium abbreviations follow Index Herbariorum Carv.-Sobr., comb. &stat. nov.urn:lsid:ipni.org:names:60474975-2Pseudobombaxgrandiflorumvar.majus A. Robyns, Bull. Jard. Bot. \u00c9tat Bruxelles 33(1): 56. 1963. \u2014 Type: Brazil. Minas Gerais: Vi\u00e7osa, Chacha Valley, near Chacha House, 17 May 1930, Y. Mexia 4711 . Basionym. Pseudobombaxgrandiflorumvar.majus based on specimens with longer pedicels and staminal tubes as well as wider calyces and petals than are found in the nominate variety. Analysis of the protologue and type material of this variety and the nominate one, along with a comprehensive examination of herbarium specimens, reveals that P.grandiflorumvar.majus is also morphologically distinct from the nominate variety in having mostly 9\u201311 (vs. mostly 5) leaflets (7 leaflets rarely occur in both taxa), often 3\u20137-flowered cymes , and 5-angulate (vs. 5-costate) fruits in cross-section. Moreover, P.grandiflorumvar.majus has calyces that are urceolate (vs. cupuliform) and often lobed (vs. truncate).Pseudobombaxgrandiflorumvar.majus inhabits semi-deciduous forests and occasionally granitic outcrops in wet forests whereas the nominate variety inhabits mainly coastal restinga vegetation. Thus, morphological evidence along with the parapatric distribution are sufficient to recognize Pseudobombaxgrandiflorumvar.majus at species rank.In addition to these morphological differences, the two taxa can be distinguished by their distribution in Eastern Brazil. Pseudobombaxmajus can be distinguished from its sister species P.longiflorum (Mart.) A. Robyns A. Robyns, Bull. Jard. Bot. \u00c9tat Bruxelles 33: 69. 1963.Bombaxmillei Standl., Trop. Woods 45: 16. 1936. \u2014 Type: Ecuador. Sept 1929, L. Mille 868 . = Pseudobombaxguayasense A. Robyns, Bull. Jard. Bot. \u00c9tat Bruxelles 33(1): 68. 1963. \u2014 Type: Ecuador. Guayas: vicinity of Guayaquil, Cerro Azul, 10 Sept 1955, E. Asplund 17588 , syn. nov. Basionym. Pseudobombaxguayasense are not sufficient to distinguish it from P.millei based on a more comprehensive sampling of herbarium collections. Previously, phylogenetic analyses of DNA sequences were interpreted as supporting the accessions examined of these two taxa as sister groups used by r groups : fig. 2,Taxon classificationPlantaeMalvalesMalvaceae(Mart.) Dugand, Mutisia 9: 4. 1952.Bombaxmunguba Mart., Nov. Gen. Sp. Pl. 1: 93, t. 99. 1826. \u2014 Type: Brazil. Amazonas: Rio Negro, Martius s.n. : 195. 1967. \u2014 Type: Brazil. Amap\u00e1: Rio Jari, near Cachoeira Miriti, 0\u00b041'N, 53\u00b06'W, 180 m, 25 Aug 1961, W. A. Egler & H. S. Irwin 46673 , syn. nov. Basionym. P.amapaense do not permit it to be distinguished from P.munguba based on a more comprehensive sampling in the field and in herbarium collections. Previously, phylogenetic analyses of DNA sequences were interpreted as supporting the accessions examined of these two taxa as sister groups used by r groups : fig. 2,"} +{"text": "AbstractPterisfauriei is widely distributed in Eastern Asia and has high morphological variation. Some morphologically similar plants related to this species are difficult to distinguish. We showed that the new Pteris species from Taiwan, previously identified as P.fauriei, can be morphologically distinguished by its wide pinnae, larger terminal pinnae than the lateral pinnae in sterile fronds, and triangular basal segments of the lateral pinnae. It was confirmed that this species is phylogenetically separated from the other East Asian Pteris species, except for a morphologically distinct species P.arisanensis, by means of chloroplast genes, rbcL and matK. The new species is named as Pterislatipinnasp. nov., referring to its wide pinnae. Here, we provide a key to facilitate the identification of the morphologically similar Pteris species in Asia. The morphological descriptions, images, ecology, and distribution are also presented. Pterisfauriei Hieron. is widely distributed in Eastern Asia. Two varieties of P.fauriei have been confirmed, and both varieties have different cryptic characteristics and prefer different niches. PterisfaurieiHieron.var.fauriei, apomictic and triploid PageBreak(2n = 87), usually has herbaceous laminae and prefers cooler sites; P.faurieivar.minor Hieron., sexual and diploid (2n = 58), usually has coriaceous laminae and is found in warmer sites , P.faurieivar.minor , and P.natiensis . Several morphologically similar species in neighboring areas were also compared, including P.arisanensis, P.biaurita, P.boninensis, P.kawabatae, P.kiuschiuensis, P.laurisilvicola, P.oshimensis, P.satsumana, P.wulaiensis, and P.yakuinsularis.We examined type materials of morphologically similar taxa, including Pteris taxa with bipinnatifid laminae were sampled. Three Pteris species, P.grevilleana, P.longipinna, and P.venusta, were used as outgroups. These bipinnatifid and outgroup species belong to clades A1 and A2, respectively, according to the phylogenetic tree of Pteris (CTAB) method method . Two chlML) analyses were performed using GARLI v.2.0.1019 .The distinct morphologies that distinguished the undescribed species from other bipinnatifid irs Fig. . Furtherirs Fig. . In TaiwPterisnatiensis , also has sterile fronds with slightly larger terminal pinnae than the lateral pinnae. Its pinnae are slightly narrower than those of the undescribed species (3\u20135 cm vs. 3\u20137 cm), and the basal pinna-segments are adnate to the rachis whereas they are not adnate to the rachis in the undescribed species alignment matrix of rbcL and matK (900 bp) contained a total of 2,178 characters with 121 parsimony-informative sites. The log-likelihood score for the most likely ML tree was -5304.42470.Genetic data and the accession numbers of the sequences are listed in Appendix PageBreakPteris species with bipinnatifid laminae formed one monophyletic group (the clade of ingroup taxa), as revealed in the previous Pteris phylogeny . The undescribed taxon cpDNA differed from P.natiensis, P.wulaiensis , and P.yakuinsulariscpDNA by one nucleotide substitution, and from P.laurisilvicolacpDNA by two nucleotide substitutions. In Clade II, P.faurieivar.fauriei, P.faurieivar.minor, and P.oshimensis shared identical cpDNA sequences.The phylogenetic tree Fig. infers thylogeny . The undP.fauriei. Here, we describe the new species and delimitate P.faurieivar.fauriei and P.faurieivar.minor. The morphology of the new species is presented in Fig. Both morphological and DNA characteristics support that this taxon is a new species, rather than a variety of PageBreakTaxon classificationPlantaePolypodialesPteridaceaeY.S.Chao & W.L.Chiousp. nov.urn:lsid:ipni.org:names:77165362-1Y.-S. Chao 2092 .TAIWAN. Hsinchu County: Zhudong Town, Wuchihshan, 3 March 2013, Rhizomes short, ascending, apex scaly; scales linear lanceolate, 1\u20134 mm long, 0.2\u20130.5 mm wide, concolorous, dark brown, entire, apex long-acuminate. Fronds clustered, 30\u2013100 cm long, nearly monomorphic. Sterile fronds 30\u201370 cm long; stipes green, 2\u20134 mm thick, 10\u201330 cm long, base with persistent and scattered scales; grooved on the adaxial side; laminae widely ovate, 15\u201345cm long, 15\u201340 cm wide, bipinnatifid; 2\u20133(4) pairs lateral pinnae, pinna angle against rachis 60\u201370\u00b0, straight, basal pinnae with one pair of exaggerated basiscopic pinnules, terminal pinnae distinctly longer and wider than the lateral except basal ones; pinnae ovate-lanceolate, distinctly narrowed at base, pectinate, 8\u201321 cm long, 3\u20137 cm wide, sessile or short-petiolate, apex caudate, 1\u20134 cm long. Basal segments of the lateral pinnae triangular, the other segments of pinnae falcate, 4\u20139 mm wide, apex obtuse, margins entire; veins forked, free. Fertile fronds 50\u2013105 cm long; stipes 25\u201355 cm long; laminae ovate to widely ovate, 20\u201350 cm long, 20\u201335cm wide, bipinnatifid; 3\u20135 pairs lateral pinnae, slightly incurved or straight; terminal pinna usually wider than the lateral; pinnae 8\u201320 cm long, 2\u20136 cm wide, 1\u20134 cm long; segments of pinnae 4\u20136 mm wide, apex acute or obtuse. Sori along pinna margins, protected by pseudoindusia; spore number 32; spores tetrahedral, tan.P.-F. Lu 24585, 24586 (TAIF); Jianshi, P.-F. Lu 25108 (TAIF); Pawushan, P.-F. Lu 26666, 26673 (TAIF); Shuitien Logging Trail, L.-Y. Kuo 01 (TAIF). Miaoli County: Sintikusyu, komokwan, Yaiti Simada 5175A (HAST).TAIWAN. Hsinchu County: Guanxi, Chike Mt., Taiwan Fig. .In shaded places, understory of evergreen broad leaf forests, below 1,000 m in elevation.latipinna\u2019 refers to its wide pinnae.The specific epithet \u2018P.latipinna Y.S.Chao & W.L.Chiou, sp. nov. in Taiwan. To date, only a few small populations are recorded. However, the available information is inadequate to support the assessment of its extinction risk. According to the We investigated the distribution of P.latipinna Y.S.Chao & W.L.Chiou, sp. nov., growing understory of forests in Taiwan was found and identified in this study. Pterislatipinna is the largest PageBreakspecies among the bipinnatifid Pteris species with single-axis in Taiwan. There were 29 Pteris species recorded in the Flora of Taiwan and venation . Similarly, in Clade II, P.oshimensis does not morphologically resemble P.fauriei but share identical cpDNA sequences. More cpDNA and nuclear DNA markers are needed to clarify the relationships among these species in P.fauriei complex.Although the ploidy of origins . Pterispomictic . For thopomictic ; P.nati diploid ; P.yakutriploid ; P.arisolyploid . RemarkaPterisfauriei complex because they are morphologically similar and phylogenetically close with Pterisfauriei. All of them are distributed in Asia, mostly in Japan and Taiwan. Interestingly, distributions of most of those species are limited: Pterislatipinna and P.wulaiensis are endemic in Taiwan; P.boninensis, P.natiensis, and P.yakuinsularis are endemic in Japan (In this study, taxa in Clade I and Clade II compose in Japan . This pain Japan .P.latipinna from the similar species are used in a key for identification of this species as shown below.The traits useful for separating"} +{"text": "Scientific Reports6: Article number: 3449410.1038/srep34494; published online: 10032016; updated: 06192017M. Danielle McDonald was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Information file that accompanies the Article.The Acknowledgments section now reads:\u201cThe authors wish to thank the staff at the Colorado State University Proteomics and Metabolomics Facility for their assistance with the mass spectrometry analyses presented here as well as Patricia Blackwelder at the University of Miami Center for Advanced Microscopy for her assistance with the electron microscopy. K.L.S. is supported in part by the University of Miami Maytag Fellowship. The transcriptome work was supported by NIH grant R24 RR032658-01 to W.C.W., McDonnell Genome Institute at Washington University School of Medicine. M.D.M. was supported by NSF (IOS-0920547). M.G. is a Maytag Chair of Ichthyology and is supported by NSF (IOS 1146695)\u201d.The author contribution statement now reads:\u201cK.L.S. and M.G. designed the experiments. K.L.S. performed the experiments, analyzed the data, and wrote the manuscript. M.G., M.D.M., W.C.W. and C.M.R.L. designed and executed transcriptomic experiments. W.C.W. performed the transcriptome sequencing. C.M.R.L., A.P. and N.C. analyzed, and assembled the transcriptomic data. M.G., C.M.R.L., A.P., W.C.W. and N.C. provided edits to a draft manuscript; M.G. approved the final version\u201d."} +{"text": "Correction to:npj Microgravity (2017); doi:10.1038/s41526-017-0033-9; Published 16 November 2017The following text was added to the Author Contributions section: A.S.B., H.C.C., and A.R.B. contributed equally to the work and are considered co-first authors. This has now been corrected in the HTML and PDF versions of this Article."} +{"text": "Begonia, a species-rich genus on limestone substrates represented by no less than 60 species in southern China, using DNA sequences of nrITS and chloroplast rpL16 intron. The sampling includes 94 Begonia species encompassing most major Asian clades with a special emphasized on Chinese species.The picturesque limestone karsts across the Sino-Vietnamese border are renowned biodiversity hotspot, distinguished for extremely high endemism of calciphilous plants restricted to caves and cave-like microhabitats that have functioned as biological refugia on the otherwise harsh habitats. To understand evolutionary mechanisms underlying the splendid limestone flora, dated phylogeny is reconstructed for Asian Begonia (SVLB), including sect. Coelocentrum (19 species sampled) and five species of sect. Diploclinium, Leprosae, and Petermannia, are rhizomatous and grouped in a strongly supported and yet internally poorly resolved clade (Clade SVLB), suggesting a single evolutionary origin of the adaptation to limestone substrates by rhizomatous species, subsequent species radiation, and a strong tendency to retain their ancestral niche. Divergence-time estimates indicate a late Miocene diversification of Clade SVLB, coinciding with the onset of the East Asian monsoon and the period of extensive karstification in the area.Except for two tuberous deciduous species and a species with upright stems, a majority of Sino-Vietnamese limestone Begonia sect. Coelocentrum is recircumscribed and expanded to include other members of the Clade SVLB . Because species of Clade SVLB have strong niche conservatism to retain in their ancestral habitats in cave-like microhabitats and Begonia are generally poor dispersers prone to diversify allopatrically, we propose that extensive and continuous karstification of the Sino-Vietnamese limestone region facilitated by the onset of East Asian monsoon since the late Miocene has been the major driving force for species accumulation via geographic isolation in Clade SVLB. Morphologically species of Clade SVLB differ mainly in vegetative traits without apparent adaptive value, suggesting that limestone Begonia radiation is better characterized as non-adaptive, an underappreciated speciation mode crucial for rapid species accumulations in organisms of low vagility and strong niche conservatism.Based on our phylogenetic study, The online version of this article (doi:10.1186/1999-3110-55-1) contains supplementary material, which is available to authorized users. DC., Petermannia (Klotzsch) A. DC., Platycentrum (Klotzsch) A. DC., Parvibegonia A. DC., Reichenheimia (Klotzsch) A. DC., Sphenanthera (Hassk.) Warb., and Symbegonia (Warb.) L.L. Forrest & P.M. Hollingsworth, accounting for 95% of the species diversity or polyphyly of most big sections , Diploclinium (41 spp.), and Platycentrum (62 spp.) accounting for the majority (88.6%) of the species diversity. Among these, ca. 60 species (35% of the Begonia diversity in China) are known primarily from limestone substrates in Guangdong (1 species), Guangxi (44 species), Guizhou (3 species) and Yunnan (19 species) provinces Y.M. Shui , one species of sect. Petermannia of the Sino-Vietnamese karst region , eight species of sect. Baryandra A. DC. (BAR), 19 species of sect. Coelocentrum (COL), 12 species of sect. Diploclinium (DIP), one species of sect. Haagea (Klotzsch) A. DC. (HAA), four species of sect. Leprosae (T.C. Ku) Y.M. Shui (LEP), one species of sect. Parvibegonia A. DC. (PAR), 25 species of sect. Petermannia (PET), 14 species of sect. Platycentrum (PLA), three species of sect. Reichenheimia (REI), one species of sect. Ridleyella Irmsch. (RID), three species of sect. Sphenanthera (SPH), one species of sect. Symbegonia (SYM), and B. boisiana Gagnep., which is assigned to sect. Petermannia by Kiew , amplification was performed in a total volume of 25\u00a0\u03bcl, including 12.5\u00a0\u03bcl of Taq DNA Polymerase Master Mix Red , 1\u00a0\u03bcl of each forward and reverse primer (10\u00a0\u03bcM), 2\u00a0\u03bcl of template DNA, and 8.5\u00a0\u03bcl of ddH2O. For ITS, the primers 5P and 26S1Rev primers were designed to optimize PCR amplification (rpL16-F and rpL16-R) and sequencing (Beg_rpL16 and rpL16-R) in Begonia. PCR reactions were carried out by a denaturation-step in 94\u00b0C for 5\u00a0min, 30 thermo-cycles of 94\u00b0C for 30\u00a0s, 60\u00b0C for 30\u00a0s, and 72\u00b0C for 90\u00a0s (60\u00a0s for ITS), and a final extension in 72\u00b0C for 5\u00a0min. PCR products were purified using QIAquick PCR purification Kit and then sequenced using an ABI PRISM dye terminator cycle sequencer, model 3700 .Two DNA sequence regions were used: the nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS) region and the chloroplast DNA http://www.phylo.org/index.php/portal/). The matrix was partitioned with a gamma model of rate heterogeneity and proportion of invariable sites estimated by the program. The program MrBayes v3.1.2 centered in the Philippines recently classified under the recircumscribed sect. Baryandara for Clade 49 to account for HPDs of age estimates of the original analysis. The tree prior was set to the Yule process and a single uncorrelated-rates relaxed molecular clock model assuming a lognormal distribution of rates (UCLD) was applied to all partitions. Two independent runs of BEAST analyses were conducted, each with 50 million generations and sampling every 1,000th generation.The software package BEAST v1.6.1 (Drummond and RambautrpL16: 1110\u00a0bp), of which 29% of the aligned sequences (31.6% in ITS and 26.9% in rpL 16) were excluded because of uncertain alignment. MP analyses yielded 149503 equally parsimonious trees of 3480 steps . For BI analyses, AIC selected the model GTR+G+I for ITS and GTR+G for rpL16.Information of sequence variability in each partition is summarized in Table\u00a0P\u2009=\u20090.001) indicates significant incongruence between ITS and the rpL16 data sets. However, because ILD test has been doubted for generating misleading conclusions under certain circumstances . Nevertheless, supports for the conflict relationships between ITS (and the concatenated) and rpL16 topologies are all less than 50% and the combined data set has much higher support values for most clades, suggesting a \u2018soft incongruence\u2019 are considered as moderate, well, and strongly supported relationships, respectively. For BI analyses, the threshold for a well-supported clade is 95% PP. The best scored ML tree (ML optimization likelihood\u2009=\u2009-20967.197060), with bootstrap support values (PB and LB) and the posterior clade probabilities (PP), is depicted in Figure\u00a0Begonia species form a moderately supported clade (LB: 74) with strong support in BI analysis (PP: 0.97). Within the Asian Clade, the Indian species B. dipetala Graham (sect. Haagea) is sister to a clade composed of all the remaining Asian species, though lacking support . This grade, corresponding well (except for sect. Parvibegonia) to the DIP I grade in Thomas et al. , five Chinese species , and one species of Taiwan (sect. Diploclinium: B. ravenii C.I Peng & Y.K. Chen). Clade PLA-SPH is mainly composed of species of sect. Platycentrum and Sphenanthera, plus one species of sect. Leprosae (B. longicarpa K.Y. Guan & D.K. Tian) and two species of sect. Diploclinium . Of the Chinese species of the DIP I grade, B. chingii and B. parvula are distributed exclusively on limestone substrates of Guangxi and Yunnan, respectively, while B. grandis is the most widespread Begonia species in China found in a variety of habitats including limestone and three strongly . Clade D1 consists of three species restricted to limestone outcrops: B. bataiensis Kiew (sect. Leprosae) from southwestern Vietnam from Peninsular Malaysia and B. peltatifolia H.L. Li (sect. Diploclinium) endemic to Hainan, China to include species of sect. Diploclinum centered in the Philippines and adjacent SE Asian islands except for B. sinofloribunda, which is nested within Clade SVLB with strong supports . With the addition of B. sinofloribunda, a rhizomatous species distributed in southern Guangxi, the clade of Sino-Vietnamese limestone Begonia (Clade SVLB) encompasses all sampled rhizomatous limestone Begonia distributed in southern China and northern Vietnam, including all sampled species of sect. Coelocentrum, two species of sect. Leprosae (B. leprosa Hance and B. cylindrica D.R. Liang & X.X. Chen), and two species of sect. Diploclinium . Within the strongly supported Clade SVLB, phylogenetic resolutions are low and weakly supported generated by the BEAST software are shown in Figure\u00a02Coelocentrum, Petermannia, and Baryandra (= DIP II), was estimated to be 12.64 mya, with the HPD date ranging from 8.54 to 16.67 mya. For Clade SVLB the mean divergent crown age was estimated to be 8.06 mya, with the HPD date ranging from 5.09 to 11.21 mya and the rest of Asian Begonia, while B. dipetala was placed sister to Clades B\u2009+\u2009C1\u2009+\u2009C2 with weak support in Thomas et al. of Clade D is monophyletic with strong support with Clade PET I basal to the subclade encompassing Clades PET II, BRA (sect. Bracteibegonia A. DC.), DIP II . It is worth to mention, however, that Clade BAR is the basal clade of the Platycentrum-Sphanenthera clade in Tebbitt et al. in present study, supports for relationships of these deep nodes are low, indicating that they are mostly soft incongruence , two species of sect. Leprosae , and one species of sect. Petermannia (B. sinofloribunda). Despite being one of the biggest (47 species) and morphologically most diverse sections in China, only three rhizomatous species of sect. Diploclinium are known from the Sino-Vietnamese limestone karsts bearing cylindric and berry-like fruits in southern China showed that sect. Leprosae is polyphyletic with its type species B. leprosa (limestone species) placed sister to sect. Coelocentrum and B. longicarpa (not limestone species) nested within clade dominated by sect. Platycentrum and Sphenanthera, suggesting that the cylindric and berry-like fruits evolved independently in the Sino-Vietnamese karsts nested within Clade SVLB, B. longicarpa in Clade PLA-SPH, and B. bataienssi sister to B. kingiana , indicate that members of Clade SVLB are uniformly characterized by the chromosomal number 2n\u2009=\u200930 Gu et al. to include B. sinofloribunda, three species of sect. Diploclinium and two species of sect. Leprosae (B. cylindrica and B. leprosa).Based on our study, although species of Clade u et al. or its tSVLB, the only Begonia species found on the Sino-Vietnamese limestone karsts are the tuberous B. chingii Irmsch. and B. grandis , and once by the rhizomatous ancestor of Clade SVLB mya mainly distributed in Guangxi, inhabit the \u2018twilight zone\u2019 adapted to and flourishing in the cave-like microhabitats. However, cave-like microhabitats are fragile and collapsed constantly due to the processes of karstification whose populations mainly differentiate via isolation-by-distance (IBD) and allopatric speciation has been the primary mode responsible for species diversification because of their low vagility and strong niche conservatism in fragmented landscapes : 127, 129. 1999; Shui et al., Bot. Bull. Acad. Sin. 43: 314. 2002; Gu, Fl. China 13: 205. 2007. LECTOTYPE SPECIES: B. porteri H. L\u00e9v. & Vaniot (designated by Barkley and BaranovBegonia sect. Leprosae (T.C. Ku) Y.M. Shui, Bot. Bull. Acad. Sin. 43: 321. 2002, syn. nov.Herbs monoecious, terrestrial, perennial, rhizomatous without erect stems and tubers, acaulescent, rhizome herbaceous or slightly woody. Leaves alternate, variable, mostly broadly ovate, oblique at base, rarely palmate, palmately compound, or occasionally peltate, glabrous to tomentose, often variegated. Inflorescence axillary, cymose , rarely thyrsoid, staminate flowers basal and carpellate flowers distal, protandrous. Perianth segments free, usually white or pink, rarely greenish or yellowish. Staminate flower with 4, or rarely 2 tepals. Carpellate flowers usually with 3 tepals, rarely 2 or 5 (\u20136); ovary 3-winged, or rarely unwinged, wings equal to unequal in fruit, mostly 1-locular, parietal placentation, rarely 3-locular with axile placentation. Fruit a 3-winged capsule, nodding, or rarely berry-like, cylindric.Cytology. 2n\u2009=\u200930 or rarely 45 and northern Vietnam, at elevations between ca. 100 and 1,300\u00a0m.Species Included and Distribution\u2014B. arachnoidea C.I Peng, S.M. Ku & Yan Liu (China: Guangxi), B. asteropyrifolia Y.M. Shui & W.H. Chen (China: Guangxi), B. aurantiflora C.I Peng, Yan Liu & S.M. Ku (China: Guangxi), B. auritistipula Y.M. Shui & W.H. Chen (China: Guangxi), B. austroguangxiensis Y.M. Shui & W.H. Chen (China: Guangxi), B. babeana Aver. & H.Q. Nguyen (Vietnam), B. bamaensis Yan Liu & C.I Peng (China: Guangxi), B. biflora T.C. Ku , B. \u00d7breviscapa C.I Peng, Yan Liu & S.M. Ku (China: Guangxi), B. cavaleriei H. L\u00e9v. , B. chongzuoensis Yan Liu, S.M. Ku & C.I Peng (China: Guangxi), B. cirrosa L.B. Sm. & Wassh. , B. crystallina Y.M. Shui & W.H. Chen (China: Yunnan), B. curvicarpa S.M. Ku, C.I Peng & Yan Liu (China: Guangxi), B. cylindrica D.R. Liang & X.X. Chen (China: Guangxi), B. daxinensis T.C. Ku (China: Guangxi), B. debaoensis C.I Peng, Yan Liu & S.M. Ku (China: Guangxi), B. fangii Y.M. Shui & C.I Peng (China: Guangxi), B. ferox C.I Peng & Yan Liu (China: Guangxi), B. filiformis Irmsch. (China: Guangxi), B. fimbribracteata Y.M. Shui & W.H. Chen (China: Guangxi), B. guangxiensis C.Y. Wu (China: Guangxi), B. huangii Y.M. Shui & W.H. Chen (China: Yunnan), B. jingxiensis D. Fang & Y.G. Wei (China: Guangxi), B. kui C.I Peng (Vietname), B. lanternaria Irmsch. , B. leprosa Hance , B. liuyanii C.I Peng, S.M. Ku & W.C. Leong (China: Guangxi), B. longgangensis C.I Peng & Yan Liu (China: Guangxi), B. longistyla Y.M. Shui & W.H. Chen (China: Yunnan), B. luochengensis S.M. Ku, C.I Peng & Yan Liu (China: Guangxi), B. luzhaiensis T.C. Ku (China: Guangxi), B. mashanica D. Fang & D.H. Qin (China: Guangxi), B. masoniana Irmsch. , B. morsei Irmsch. (China: Guangxi), B. nahangensis Aver. & H.Q. Nguyen (Vietnam), B. ningmingensis D. Fang, Y.G. Wei & C.I Peng (China: Guangxi), B. ningmingensis var. bella D. Fang, Y.G. Wei & C.I Peng (China: Guangxi), B. obliquifolia S.H. Huang & Y.M. Shui (China: Yunnan), B. ornithophylla Irmsch. (China: Guangxi), B. pengii S.M. Ku & Yan Liu (China: Guangxi), B. phuthoensis H.Q. Nguyen (Vietnam), B. picturata Yan Liu, S.M. Ku & C.I Peng (China: Guangxi), B. platycarpa Y.M. Shui & W.H. Chen (China: Yunnan), B. porteri H. L\u00e9v. & Vaniot , B. porteri var. macrorhiza Gagnep. (Vietnam), B. pseudodaxinensis S.M. Ku, Yan Liu & C.I Peng (China: Guangxi), B. pseudodryadis C.Y. Wu (China: Yunnan), B. pseudoleprosa C.I Peng, Yan Liu & S.M. Ku (China: Guangxi), B. pulvinifera C.I Peng & Yan Liu (China: Guangxi), B. retinervia D. Fang, D.H. Qin & C.I Peng (China: Guangxi), B. rhynchocarpa Y.M. Shui & W.H. Chen (China: Yunnan), B. rugosula Aver. (Vietnam), B. semiparietalis Yan Liu, S.M. Ku & C.I Peng (China: Guangxi), B. setulosopeltata C.Y. Wu (China: Guangxi), B. sinofloribunda Dorr (China: Guangxi), B. sonlaensis Aver. (Vietnam), B. subcoriacea C.I Peng, Yan Liu & S.M. Ku (China: Guangxi), B. suboblata D. Fang & D.H. Qin (China: Guangxi), B. umbraculifolia Y. Wan & B.N. Chang (China: Gaungxi), B. variifolia Y.M. Shui & W.H. Chen (China: Guangxi), B. wangii T.T. Yu , B. zhengyiana Y.M. Shui (China: Yunnan).B. wangii T.T. Yu, previously assigned to sect. Diploclinium Additional file 1:Authors\u2019 original file for figure 1Authors\u2019 original file for figure 2Below are the links to the authors\u2019 original submitted files for images."} +{"text": "Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices\u2014such as clove, oregano, thyme, cinnamon, and cumin\u2014possessed significant antibacterial and antifungal activities against food spoilage bacteria like Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa)\u2014has increased rapidly, causing the increase of morbidity and mortality [Listeria monocytogenes (L. monocytogenes) in food products or delay the growth of spoilage microorganisms [Microbial pathogens in food may cause spoilage and contribute to foodborne disease incidence, and the emergence of multidrug resistant and disinfectant resistant bacteria\u2014such as ortality . Weak acortality , which aortality , can resortality . Moreoverganisms . Naturalrganisms . The antS. aureus, aggravates the emerging antibiotic resistance [Morbidity and mortality are mainly caused by infectious diseases all over the world. The World Health Organization reported that 55 million people died worldwide in 2011, with one-third of the deaths owing to infectious diseases . Antibiosistance . TherefoSpices have been used as food and flavoring since ancient times , and as This review summarizes the scientific studies on the antibacterial and antifungal activities of spices and their derivatives, and some suggestions and prospects are offered for future studies.Eugenia caryohyllata), belonging to family Myrtaceae, is widely used in medicine as antiseptic against infectious diseases like periodontal disease due to the antimicrobial activities against oral bacteria [Clove [S. aureus (minimum inhibitory concentration (MIC): 2 mg/mL) and E. coli (MIC: 2.5 mg/mL). While in vivo, the study was conducted in 40 adult male albino rats, and the results confirmed the efficacy of clove extract as natural antimicrobials. The direct antimicrobial activities of ultra-fine powders of ball-milled cinnamon and clove were tested by Kuang et al. [E. coli, S. aureus, Brochothrix thermosphacta (B. thermosphacta), Lactobacillus rhamnosus (L. rhamnosus), and Pseudomonas fluorescens (P. fluorescens) from meat, using broth dilution method. Clove powder showed strong inhibitory effects on five microorganisms tested with the MICs ranging from 1.0% w/v (L. rhamnosus and B. thermosphacta ) to 2.0% w/v (P. fluorescens), and the inhibitory effects were positively associated with the concentrations of powder, which increased from 0.5% to 2.5% w/v.Antimicrobial activities of clove water extract were studied in vitro and in vivo against pathogenic microorganisms (phritis) . An in vg et al. against Bacillus cereus (B. cereus) and has the ability of cell wall deterioration and cell lysis [Clove could destroy cell walls and membranes of microorganisms, and permeate the cytoplasmic membranes or enter the cells, then inhibit the normal synthesis of DNA and proteins . Eugenolll lysis .Candida albicans isolates, of which 12 were isolated from oropharynges, 16 from vaginas, and 10 from damaged skin, using the microdilution method. Clove EO possessed the strongest antifungal activities against all C. albicans strains among the tested spices. Pure eugenol alone exhibited weaker antifungal activities than clove leaf EO. Angienda et al. [Salmonella typhimurium (S. typhimurium), E. coli, B. cereus, and Listeria innocua (L. innocua) by agar diffusion test. Clove EO showed the most effective inhibition against both Gram-positive bacteria and Gram-negative bacteria compared with three other EOs, with the MICs ranging from 1.25% v/v (B. cereus) to 2.50% v/v (S. typhimurium and E. coli). Lomarat et al. [Morganella morganii (M. morganii), by determining MICs and minimum bactericidal concentrations (MBCs) using the broth dilution assay, and also found the antibacterial compounds of EOs by bioautography-guided isolation. The results indicated that the clove EO was the most effective against M. morganii among nine tested spices with MIC 0.13% v/v and MBC 0.25% v/v. The eugenol was identified as the active component of clove EO by thin layer chromatography bioautography assay.Badei et al. tested ta et al. investigt et al. reportedL. monocytogenes, S. aureus, and Salmonella enterica (S. enterica) in raw pork by counting bacterial enumeration. When treated with clove extract, raw pork samples were found with the fewest colonies of tested bacteria. Bayoub et al. [L. monocytogenes, the MICs were determined by agar well diffusion test. The results showed that clove extract was the most effective inhibitor against L. monocytogenes compared with the other 12 selected plant ethanol extracts, with the MIC 0.24 mg/mL. Cui et al. [Clostridium spp. Clove water extract was found with the greatest antimicrobial activity against Clostridium botulinum in trypticase peptone glucose yeast extract broth (pH = 7.0) among all the water extracts, and the MICs of clove extract ranged from 0.1% to 0.2% against Clostridium spp. Antimicrobial effects of 3 extracts of 12 plants were tested on 2 fungi (Kluyveromyces marxianus (K. marxianus) and Rhodotorula rubra (R. rubra)) and 8 bacteria (Klebsiella pneumoniae (K. pneumoniae), Bacillus megaterium (B. megaterium), P. aeruginosa, S. aureus, E. coli, Enterobacter cloacae (E. cloacae), Corynebacterium xerosis (C. xerosis), and Streptococcus faecalis ) by the disc diffusion method [K. pneumoniae. The acetone extract showed inhibition against microorganisms (DIZs: 8\u201318 mm) tested except R. rubra and K. pneumoniae. The ethyl acetate extract only showed antibacterial activity against B. megaterium (DIZ: 7 mm). Liang et al. [v/v in the cider for clove oil and 2% w/w for clove powder at room temperature. Badhe et al. [S. aureus, S. typhimurium, E. coli, and B. cereus at refrigerated temperature (8 \u00b1 2 \u00b0C) for intervals of 0, 3, 6, 12, 24, and 48 h. The results indicated that at the concentration of 2%, clove powder showed highest effect on S. aureus followed by E.coli and S. typhimurium, and at 24 h under refrigeration, clove powder led to a significant reduction of bacteria counting.Shan et al. tested tb et al. reportedi et al. tested tn method . Clove eg et al. observede et al. tested tE. coli, S. typhimurium, S. aureus, B. cereus, and L. monocytogenes. The films prepared by low molecular mass chitosan with 2% EO and ethyl heptanoate extract from clove showed antimicrobial activities against a majority of the tested strains. In another study, the researchers tested the antimicrobial activities of EOs and functional extracts of cumin, clove, and elecampane against E. coli, S. typhimurium, B. cereus, S. aureus, and L. monocytogenes by determining the MICs and MBCs [L. monocytogenes (MIC of 750 mg/L) and ethyl heptanoate extract of clove against B. cereus (MIC of 250 mg/L). Among the chitosan films added with EOs, only clove showed inhibition zones of all tested bacteria except L. monocytogenes. The ethyl heptanoate extract of clove film also possessed antibacterial activities against all tested bacteria, weaker than those of clove EO though. Liu et al. [v/v against Enterobacteriaceae, S. aureus, and Pseudomonas sp., respectively. Spice EOs possessed the ability to decrease the number of spoilage populations, but not the species diversity of spoilage microbiota.Clove EO and its functional extracts have been incorporated into films, the antimicrobial activities of which have been evaluated in some studies. In a study, chitosan at high, moderate and low molecular mass were elaborated with antimicrobial films which were incorporated with EOs and extracts from two spices . Then thand MBCs . They alu et al. evaluateP. fluorescens, S. typhimurium, E. coli, B. cereus, and L. innocua. Generally speaking, the qualities of the papers cited are good and the results are reliable.Collectively, clove EO and extracts could prevent against some food spoilage and foodborne pathogens , especiaOriganum vulgare), belonging to family Lamiaceae, has been used as food seasoning and flavoring for a long time. The major components associated with antimicrobial activities in oregano EO were proved to be carvacrol and thymol [Oregano , Salmonella enteritidis (S. enteritidis), and S. typhimurium, respectively. Santoyo et al. [S. aureus, Bacillus subtilis (B. subtilis), E. coli, P. aeruginosa, C. albicans, and Aspergillus niger (A. niger)), using the disk diffusion and broth dilution methods. The results showed that all of the supercritical fluid extraction fractions exhibited antimicrobial effects on tested microorganisms, and the most efficient fraction was obtained with 7% ethanol at 150 bar and 40 \u00b0C. De Souza et al. [C. albicans, Candida krusei (C. krusei), Candida tropicalis , B. cereus, E. coli, S. aureus, Yersinia enterocolitica (Y. enterocolitica), S. enterica, and Serratia marcescens (S. marcescens)), using the solid medium diffusion procedure. The results indicated that heating treatment showed no significant effects on the antimicrobial activities of EO, with the DIZs and MICs of heated EO close to those of EO kept at room temperature (MICs ranging from 10 to 40 \u03bcL/mL).Babacan et al. evaluateo et al. observeda et al. evaluateC. albicans strains [Oregano could bind to sterols in the fungal membranes of strains , but the strains . As the Fusarium oxysporum f. sp. phaseoli, Macrophomina phaseoli (M. phaseoli), Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani), Alternaria solani (A. solani), and Alternaria parasiticus (A. parasiticus)). The results showed that the mycelial growth were 100% inhibited by 10% oregano decoction in culture medium. Ai-Turki et al. [E. coli and B. subtilis using the disc diffusion method. Oregano extract showed the best antibacterial effects on two bacteria compared with three other spice extracts, and B. subtilis showed more sensitivity than E. coli. Marques et al. [S. aureus isolated from poultry meat using the disk diffusion method, and the MICs and MBCs were tested using the microdilution technique. All the S. aureus strains were susceptible to oregano EO with the MICs ranging from 6.25 to 25 \u03bcL/mL, but four of the isolates were resistant to ampicillin and one was resistant to tetracycline. Bozin et al. [P. aeruginosa and E. coli. Viuda-Martos et al. [Lactobacillus curvatus (L. curvatus), Lactobacillus sakei (L. sakei), Staphylococcus carnosus (S. carnosus), Staphylococcus xylosus (S. xylosus), Enterobacter gergoviae (E. gergoviae) and Enterobacter amnigenus (E. amnigenus)), using the disc diffusion method. Oregano EO was the most effective against bacteria tested, with DIZs ranging from 35.29 mm (S. xylosus) to 57.90 mm (E. amnigenus). Santurio et al. [E. coli strains isolated from poultry and cattle faeces by determining the MICs using the broth microdilution technique. The results showed that the most effective against all E. coli strains in the study was oregano EO. Khosravi et al. [Artemisia sieberi and oregano EOs against Candida glabrata (C. glabrata) isolated from patients with vulvovaginal candidiasis by determining the MICs and minimal fungicidal concentrations (MFCs), using the broth macrodilution method. The results indicated that the EOs inhibited all tested C. glabrata isolates concentration-dependently, with the MICs ranging from 0.5 to 1100 \u03bcg/mL (mean: 340.2 \u03bcg/mL) for oregano. Dal Pozzo et al. [Staphylococcus spp. isolates from herds of dairy goats, by determining the MICs and MBCs using the broth microdilution method. Oregano and thyme possessed equally strong antimicrobial activities among EOs. Santos et al. [S. aureus and E. coli isolated from vongole and bacteria standard ATCC (American Type Culture Collection): E. coli, S. aureus, and Salmonella choleraesuis (S. choleraesuis), by determining the MICs using diffusion test. Oregano and clove EOs presented antimicrobial activities against all tested bacteria, but oregano presented larger DIZs of 26.7 mm (E. coli) and 29.3 mm (S. aureus). Hyun et al. [Ozcan et al. investigi et al. tested ts et al. assessedn et al. investigs et al. studied o et al. reportedi et al. investigo et al. studied s et al. evaluaten et al. tested tL. monocytogenes and E. coli were evaluated in vitro by agar diffusion test [L. monocytogenes, 3.6\u20134 log reduction of L. monocytogenes, and 3 log reduction of E. coli were observed in films incorporated with 1% and 2% oregano EO.The antimicrobial effects of pure EOs of four spices and chitosan-EOs films on ion test . The antStaphylococcus spp. and S. aureus isolates with larger DIZs and lower MICs, MBCs, and MFCs compared with several other spices , belonging to family Lamiaceae, is a subshrub native to the western Mediterranean region. Thyme is widely used as a spice to add special flavor to foods. In recent studies, thyme was found to possess efficient antimicrobial activities and was used in some foods to extend the shelf-life [Thyme , P. aeruginosa, E. coli, and Mycobacterium smegmatis (M. smegmatis)) and fungal strains [Thymus species were determined by agar diffusion method [T. vulgaris and T. serpyllum EOs were the most efficient as they inhibited all the tested bacteria , L. innocua, and Streptococcus pyogenes (S. pyogenes)) and yeasts ) both at original and half-diluted concentrations. P. aeruginosa, L. innocua, and S. pyogenes were highly and equally sensitive to the Thymus oils, while C. sakazakii exhibited limited sensitivity, and the sensitivity of the two yeast strains were similar to that of C. sakazakii, but S. cerevisiae was a little more sensitive than C. albicans.A study evaluated the antimicrobial activities of thyme EO against bacteria . Thyme Eginalis) . The resn method . T. vulgE. coli and increased extracellular ATP, which could disrupt the function of plasma membranes [The major active compound of thyme is thymol, which exerted its antimicrobial action through binding to membrane proteins by hydrophobic bonding and hydrogen bonding, and then changing the permeability of the membranes . Thymol embranes . As thymembranes , the exaB. subtilis and S. enteritidis, using the agar disk diffusion method. Thyme hydrosol demonstrated more significant inhibitory effects on B. subtilis and S. enteritidis than sage, peppermint, and black pepper hydrosols, with the mean DIZs 20 mm for B. subtilis and 15 mm for S. enteritidis. According to another study, the antimicrobial effects of the six plant hydrosols on S. aureus, E. coli, S. typhimurium, P. aerugenosa, and C. albicans were tested by determining the microbial growth zones on hydrosol agar plates and control agar plates [E. coli and S. typhimurium, but C. albicans was inactive to the tested hydrosols. Girova et al. [P. fluorescens, Pseudomonas putida (P. putida), P. fragi, B. thermosphacta, and C. albicans) isolated from spoiled chilled meat products and some reference strains 561, P. aeruginosa ATCC 9027, and C. albicans ATCC 10231) using the method of disc diffusion and serial broth dilution. The results indicated that the antimicrobial effects of the EOs were equal at 37 \u00b0C and 4 \u00b0C. Thyme EO exhibited the highest antimicrobial activities with the MICs ranging from 0.05% to 0.8% w/v. Hajlaoui et al. [Vibrio alginolyticus activities of five aromatic plant EOs using agar well diffusion test, and the MICs and MBCs were examined using the broth microdilution susceptibility method. Thyme EO was proved to be the most efficient against 13 V. alginolyticus strains compared with 4 other EOs, with the MICs ranges of 0.078\u20130.31 mg/mL and MBCs ranges of 0.31\u20131.25 mg/mL. Also, Viuda-Martos et al. [L. innocua, S. marcescens, and P. fluorescens) and the concentration effects of five spice EOs using the agar disc diffusion method. Only the EO of thyme showed inhibitive effects on all tested bacteria at all added doses . Aliakbarlu et al. [Thymus kotschyanus, Ziziphora tenuior, and Ziziphora clinopodioides, against two Gram-positive bacteria (B. cereus and L. monocytogenes) and two Gram-negative bacteria (S. typhimurium and E. coli), using the agar disc diffusion and micro-well dilution assay. The EO of thyme showed the highest antibacterial activities, with the widest inhibition zones and the lowest MICs (0.312\u20131.25 \u03bcL/mL), and B. cereus was the most sensitive bacterium tested. Hyun et al. [T. vulgaris) EO and thyme-2 EO exerted the highest antibacterial activities against 18 pathogenic bacteria strains compared with other spices, except for P. aeruginosa. Thyme-1 EO also demonstrated the best antibacterial effects on spoilage bacteria. In addition, the antimicrobial effects of 17 spices and herbs against Shigella strains were tested in another study [w/v for the Shigella strains. The study also used various combinations of temperatures , pH values , and NaCl concentrations , and the inclusion or exclusion of thyme or basil at 1% w/v in a Mueller\u2013Hinton agar model system to test the inhibitory effects of thyme and basil. In the presence of thyme, Shigella flexneri (S. flexneri) did not develop Colony-Forming Units (CFU) during the seven-day incubation period for 16 of the 18 tested combinations.Al-Turki et al. reportedr plates . The resa et al. assessedi et al. observeds et al. assessedu et al. evaluaten et al. investigS. aureus, S. epidermidis, E. coli, Klebsiella spp., P. aeruginosa, Enterobacter aerogenes (E. aerogenes), Proteus vulgaris (P. vulgaris), and Enterobacter sakazakii (E. sakazakii) using the disc diffusion halo test. For Gram-positive species, thyme extracts only presented activity against S. epidermidis, and hydroalcoholic extract showed a lower antibacterial activity than decoction and infusion extracts, which showed the similar activities. For Gram-negative species, thyme extracts showed antimicrobial activities in the order of E. coli > P. vulgaris, P. aeruginosa > E. aerogenes = E. sakazakii; decoction and hydroalcoholic extracts had similar effects against the bacteria except P. aeruginosa, while the lowest activity was observed in infusion extracts. Moreover, the antifungal effects of thyme EO, hydrosol and propolis extracts on natural mycobiota on the surface of sucuk were evaluated [w/v, in water), thyme EO , and propolis extract reduced by 4.88, 2.45, and 2.05 log CFU/g in yeast-mold counting compared with sterile water, respectively.Some studies compared the antimicrobial activities of different extracts of thyme. Martins et al. evaluatevaluated . The resCandida lusitaniae (C. lusitaniae) on different concentrations of nisin (0.1\u20133 mmol/L), thymol (0.02\u20131.5 mmol/L), carvacrol (0.02\u20131 mmol/L), or cymene (0.02\u20133 mmol/L) in broths , and also evaluated the inhibitory activity of thymol against C. lusitaniae in tomato juice. Thymol, carvacrol, and cymene totally inhibited the yeast growth for more than 21 days at 25 \u00b0C when the concentrations were higher than 1 mmol/L. Compared with the control without thymol, the activity of thymol against C. lusitaniae in tomato juice was significant.Aman et al. analyzedS. aureus and E. coli, with low MICs (\u22641100 \u03bcL/mL) .Cinnamomum zeylanicum), belonging to family Lauraceae, is widely applied in savory dishes, pickles, and soups [Cinnamon were evaluated in a study by scanning electron microscopy and laser scanning confocal microscopy analyses [The antimicrobial activities of cinnamon were evaluated in some studies. Gupta et al. comparedn et al. tested tanalyses . CinnamoThe major component of cinnamon, cinnamaldehyde, possesses antimicrobial effects on microorganisms, as it inhibited cell wall biosynthesis, membrane function, and specific enzyme activities. More specific cellular targets of cinnamaldehyde are still required to be studied in detail .A. niger, Fusarium sambucinum (F. sambucinum), Pythium sulcatum (P. sulcatum), and Rhizopus stolonifera (R. stolonifera)). At the concentration of 0.05 g/mL, cinnamon extract totally inhibited A. niger and P. sulcatum, while at the level of 0.10 and 0.15 g/mL F. sambucinum and R. stolonifer were completely inhibited, respectively. Another study conducted by Wang et al. [S. aureus, Lactobacillus sp., B. thermosphacta, Pseudomonas spp., and E. coli) by the aerobic plate count method and disc diffusion. Cinnamon aqueous extract was the only one to inhibit all the tested microorganisms at the concentration of 1% w/v. The inhibitory effects were stronger with the increase of extract concentrations from 1% to 5% w/v. In the same way, the antimicrobial activities of the hydrosols of six spices against five microorganisms were tested [v/v hydrosol, 10\u201366.5% at 10% v/v hydrosol, and 10\u2013100% at 15% v/v hydrosol against microorganisms tested except C. albicans. Moreover, S. aureus was the most sensitive strain to cinnamon hydrosol, while P. aeruginosa was the least sensitive strain. Agaoglu et al. [S. aureus, K. pneumoniae, P. aeruginosa, E. coli, Enterococcus faecalis , M. smegmatis, Micrococcus luteus (M. luteus), and C. albicans), by the disc diffusion. Among all the spices tested, only cinnamon exerted inhibitory activities against all the tested microorganisms. S. aureus and C. albicans were the most sensitive to cinnamon, while E. coli was the least. Keskin et al. [P. aeruginosa and R. rubra, and the acetone extract showed inhibition against tested microorganisms except R. rubra. Revati et al. [Enterococci isolated from human clinical samples with the agar well diffusion method. Crude ethanol extract of cinnamon was the most effective against all the clinical isolates of Enterococci, with the DIZs ranging from 31 to 34 mm. Moreover, the antimicrobial activities of 8 spice EOs against 6 bacterial species and 10 fungal species were tested in a study using the disk diffusion assay and MICs were determined using the agar dilution test [Mvuemba et al. evaluateg et al. tested te tested . The inhu et al. examinedn et al. investigi et al. exploredion test . CinnamoA. niger, at low MICs is an aromatic plant belonging to the Apiaceae family. Cumin has been used since ancient time as an ingredient in foods in Middle East, and cumin seeds have long been used as antiseptic and disinfectant in India [Cumin roasted cumin oils had similar antimicrobial effects on microorganisms tested and were more effective than those of raw oils. Reza et al. [E. coli, P. aeruginosa, B. cereus, and S. aureus, by the agar well diffusion method and disk diffusion method. The results indicated that cumin EO exerted antibacterial effects on bacteria tested, and \u00e3-irradiation (10 and 25 kGy) to cumin seeds had no significant effects on the antimicrobial activities of cumin.In a study, the antimicrobial activities of cumin EO against methods . E. colie tested . The EO d et al. exploreda et al. studied Carum carvi L. against E. coli and the genera Pseudomonas, Clavibacter, Curtobacterium, Rhodococcus, Erwinia, Xanthomonas, Ralstonia, and Agrobacterium using the agar diffusion test. Cumin EO showed antibacterial effects on both Gram-positive and Gram-negative bacteria except Pseudomonas viridiflava, which was resistant to 8 \u03bcL EO, the highest level tested. Ozcan et al. [v/v) against S. typhimurium, B. cereus, S. aureus, E. faecalis, E. coli. Y. enterocolitica, S. cerevisiae, Candida rugosa, Rhizopus oryzae, and A. niger. The results showed that cumin EO was effective against all tested bacterial species as well as S. cerevisiae and Candida rugosa among fungi. Stefanini et al. [E. coli, P. aeruginosa, and Salmonella sp. with DIZs of 18, 10, and 23 mm, respectively. In another study, the antimicrobial activities of EOs of six spices against L. curvatus, L. sakei, S. carnosus, S. xylosus, E. gergoviae, and E. amnigenus were assessed using the agar disc diffusion method [L. sakei) to 38.17 mm (E. gergoviae). Moreover, another study evaluated the antimicrobial activities of EOs of five spices against different microorganism species by the disc diffusion method and discussed the possible effects in vitro between plants and antibiotics [Pseudomonas pyocyaneus (P. pyocyaneus) and Aeromonas hydrophila (A. hydrophila), but showed antagonistic effects against other bacteria tested. Similarly, the possible synergistic interactions of some spice EOs on antibacterial activities against six foodborne bacteria\u2014B. cereus, L. monocytogenes, M. luteus, S. aureus, E. coli, and S. typhimurium\u2014were evaluated by micro broth dilution, checkerboard titration, and time-kill methods [Chaudhry et al. determinn et al. examinedi et al. analyzedn method . Cumin Eibiotics . Cumin i methods . The resE. coli, S. aureus, and S. faecalis at low concentrations , belonging to the Lamiaceae family, is a perennial shrub with pleasant smell and grows all over the world. Rosemary has been used in pharmaceutical products and traditional medicine, and also used as a flavoring agent in food products due to its desirable flavor, antioxidant activities, and antimicrobial activities [Rosemary tested than on yeasts. Bozin et al. [C. albicans, Trichophyton tonsurans (T. tonsurans), and Trichophyton rubrum at lower MICs (15.0\u201330.2 \u03bcL). Rosemary EO also expressed important antibacterial activities on E. coli, S. typhimurium, S. enteritidis, and Shigella sonei. Weerakkody et al. [E. coli, S. typhimurium, L. monocytogenes, and S. aureus by the agar disc diffusion and broth dilution assay. The results of both methods indicated that hexane extract of rosemary exhibited significantly higher antibacterial activities than ethanol and water extracts against all bacteria tested except S. typhimurium with the MICs ranging from 1.25 to 5.0 mg/mL.Tavassoli et al. reportedn et al. identifiy et al. comparedB. cereus, E. coli, P. aeruginosa, S. aureus, and L. monocytogenes using the dilution method and the description of growth curves of the tested bacteria. Rosemary extract was proved to be the most effective at all concentrations . At the concentration of 0.01% w/w, rosemary extract only inhibited P. aeruginosa and E. coli, while the higher extract concentrations were effective against all other bacteria. Zhang et al. [L. monocytogenes, E. coli, P. fluorescens, and L. sake using the well diffusion test. Individual extract of rosemary showed strong antimicrobial activities, and the combination of rosemary and liquorice extracts showed the best inhibitory effects on all tested microorganisms. Kozlowska et al. [L. monocytogenes and S. aureus and naturally spoilage microflora on instant shrimp stored for 16 days at 4 or 8 \u00b0C. Both combinations significantly decreased the levels of aerobic bacteria and lactic acid bacteria, but showed no effects on L. monocytogenes or S. aureus. Azizkhani et al. [S. aureus, while the combination of rosemary EO and ceftriaxone antibiotics showed no effect.Additionally, Krajcova et al. observedg et al. examineda et al. tested ta et al. studied i et al. evaluatei et al. evaluateS. aureus belongs to the Liliaceae family [Garlic and raw meatballs (stored at room temperature) by determining the colony counts of total aerobic mesophilic bacteria, yeast, and molds at 2, 6, 12, and 24 h after storage . The resC. albicans [Garlic EO penetrated the cellular membranes and even the menbranes of organelles like mitochondria, damaged organelles, and resulted in the death of albicans . FurtherE. coli, 8 serotypes of Salmonella, L. monocytogenes and A. hydrophila using the agar well method and filter paper method. Garlic extract exhibited significant antibacterial activities at all concentrations against all test microorganisms except L. monocytogenes, and the activity against E. coli was linearly dependent with concentration. Joe et al. [K. pneumoniae, S. aureus, M. morgani, C. albicans, E. coli, and P. vulgaris using the filter paper assay. Garlic extract exerted superior antibacterial activities at all concentrations , especially against P. vulgaris and M. morgani, and the activities were a linear function of concentrations. Geremew et al. [E. coli, S. aureus, S. flexneri, and Streptococcus pneumoniae by the agar well diffusion method. Garlic was the most effective against all tested pathogens except S. flexneri. Among different solvent extracts used, garlic acetone extract exhibited the highest antibacterial activities. Touba et al. [S. aureus in hamburger. Samples treated with garlic aqueous extract were kept in refrigerator for one and two weeks, and were frozen for one, two, and three months, before being tested by the microbial counts. The first- and second-week samples were significantly reduced by all the 1, 2, and 3-mL extracts, which were added to 100 g hamburger samples, respectively, showing 2 and 3-mL extracts were more effective. In treatment of one, two, and three-month samples, the growth of S. aureus was significantly decreased by the 2 and 3-mL extracts. Al-Turki [B. subtilis and S. enteritidis using the agar disk diffusion method. Garlic hydrosol exhibited stronger antibacterial activities against B. subtilis and S. enteritidis compared with thyme, peppermint, sage, and black pepper hydrosols.Some studies compared the antimicrobial activities of different spices. Indu et al. studied e et al. reportedw et al. examineda et al. tested ta et al. reportedAl-Turki exploredE. coli and S. aureus , belonging to the family of Zingiberaceae [Ginger , Trichothecium roseum (T. roseum), Fusarium graminearum (F. graminearum), F. oxysporum, Fusarium oxysporum (F. monoliforme), and Curvularia palliscens, by food poison and inverted petri-plate technique. The results showed that the EO 100% inhibited F. oxysporum, while the oleoresin 100% inhibited A. niger. Park et al. [n-hexane extracts of ginger and five ginger constituents against three anaerobic Gram-negative bacteria, Porphyromonas gingivalis , Porphyromonas endodontalis, and Prevotella intermedia. The results indicated that ginger extracts exhibited antibacterial activities against three tested bacteria. Two highly alkylated gingerols showed significant inhibition against the growth of these oral pathogens with the MICs ranging from 6 to 30 \u00b5g/mL, and also killed the oral pathogens at a MBC range of 4\u201320 \u00b5g/mL. Sa-Nguanpuag et al. [B. subtilis, Bacillus nutto, P. aerugenosa, Rhodoturola sp., Samonella newport, S. enteritidis, and Fusarium sp.; except E. coli, Campylobactor coli, and Campylobactor jejuni (C. jejuni) in vitro. In the case of shredded green papaya, when the package was added with 5 and 10 \u03bcL ginger oils the growth of microorganisms was inhibited well, while with 15 \u03bcL ginger oil a reduction in growth rate was observed.Ginger was proved to possess antimicrobial activities in several studies. Singh et al. determink et al. comparedg et al. evaluateVibrio species at various temperatures. The results indicated that EOs from ginger and mustard could inhibit the growth of Vibrio parahaemolyticus and Vibrio vulnificus at 5 \u00b0C of storage. Indu et al. [E. coli, 8 serotypes of Salmonella, L. monocytogenes, and A. hydrophila by the agar well method and filter paper method. The results indicated that ginger extract possessed inhibitory effects on two serogroups of E. coli. Mvuemba et al. [A. niger, F. sambucinum, P. sulcatum, or R. stolonifera. The results demonstrated that ginger extract significantly suppressed the mycelial growth of tested microorganisms, and P. sulcatum was 100% inhibited by 0.05 g/mL of ginger extract. Touba et al. [Phoma exigua (P. exigua), Fusarium nygamai (F. nygamai), and R. solani by poisoned food technique. The results showed that hot water extracts from garlic and ginger possessed the best antifungal activities. Cold water extracts were commonly more effective than hot water extracts on tested pathogens. In another study, the antibacterial activities of 7 ethanol extracts of spices against 215 high levels gentamicin resistant enterococcal strains isolated from clinical samples were evaluated by the well diffusion method [Yoo et al. investigu et al. tested ta et al. assesseda et al. tested tn method . The resP. aerugenosa both in vivo and in vitro at low concentrations is one of the oldest spices, which is widely used in the flavoring of confectionary, baked goods, condiments, etc. Basil oil was also used in perfumery, as well as in dental and oral products [Basil , Botryodiplodia theobromae, and R. solani were assessed by the disc diffusion method and the MICs were determined by a microdilution broth susceptibility assay [P. aeruginosa, Shigella sp., L. monocytogenes, S. aureus, and two strains of E. coli, but the chloroform and acetone extracts exhibited no effects. Kocic-Tanackov et al. [Fusarium species , by the agar plate test. Basil extract showed significant activities against F. proliferatum and F. subglutinans at the concentration of 0.35 and 0.70% v/v, but showed lower activities against other tested Fusarium species. Basil extract 100% inhibited aerial mycelium of all tested Fusarium spp. at 1.50% v/v. Beatovic et al. [B. cereus, Micrococcus flavus, S. aureus and E. faecalis, E. coli, P. aeruginosa, S. typhimurium, and L. monocytogenes) and 7 fungi (Aspergillus fumigatus (A. fumigatus), A. niger, Aspergillus versicolor (A. versicolor), Aspergillus ochraceus (A. ochraceus), Penicillium funiculosum, Penicillium ochrochloron, and Trichoderma viride) by a modified microdilution technique. All basil EOs tested showed significant antimicrobial activities, with MICs ranging from 0.009 to 23.48 \u03bcg/mL for bacteria and 0.08\u20135.00 \u03bcg/mL for fungi. All the EOs showed 100-fold higher antibacterial activities than ampicillin for some bacteria, and 10- to 100-fold higher antifungal activities than the commercial antifungal agents, e.g., ketoconazole and bifonazole.In a study, the antimicrobial activities of EOs from aerial parts of basil against ty assay . The resty assay . Methanov et al. reportedc et al. investigA. flavus and aflatoxin producted by A. flavus strain. The results showed that basil EO delayed the growth of A. flavus. At 150 \u03bcL/100 mL, basil EO completely inhibited A. flavus, and effectively controlled the aflatoxin B1 production. Lomarat et al. [M. morganii, a histidine decarboxylase producing bacteria, by microdilution assay. Basil EO possessed the antibacterial activity against M. morganii , and the active compound of basil oil was methyl chavicol.El-Habib investigt et al. tested tA. flavus , belonging to family Umbellifarae [Fennel strains were tested [S. mutans strains tested were completely inhibited by fennel seeds EOs at concentrations higher than 80 ppm. Diao et al. [Streptomyces albus , B. subtilis, S. typhimurium, Shigella dysenteriae (S. dysenteriae). and E. coli, among which S. dysenteriae was the most sensitive with the lowest MIC (0.125 mg/mL) and MBC (0.25 mg/mL). In another study, the antimicrobial activities of crude extract of fennel was determined using the agar diffusion method against E. coli, S. blanc, P. merabilis, P. vulgaris, S. epidemidis, S. saprophyticus, A. versicolor, A. fumigates, and Penicilium camemberti [A. niger, A. flavus, F. graminearum, and Fusarium moniliforme (F. moniliforme) at 6 \u03bcL (in 20 mL culture medium), and it was effective on A. niger even at 4 \u03bcL.In a study, the antibacterial activities of fennel seeds EO against e tested . The reso et al. also detmemberti . The resmemberti . The resS. dysenteriae and result in the leakage of electrolytes, losses of proteins, reducing sugars, etc., and eventually lead to the decomposition and death of cells [Fennel seed EO could break the permeability of cell membrane of of cells .S. typhimurium and E. coli were compared by the disc diffusion method and dilution method [v/v against S. typhimurium and E. coli, respectively. Nguyen et al. [B. subtilis, E. faecalis, L. innocua, E. coli, P. putida, Providencia stuartii, and Acetobacter calcoaceticus by the Kirby-Bauer disc diffusion method. Methanol and ethanol extracts from fennel seeds exhibited the best antimicrobial effects with the largest DIZs on six out of the seven bacteria except E. coli.The antimicrobial activities of cumin and fennel EOs on n method . Fennel n et al. evaluateS. dysenteriae, S. typhimurium, and E. coli , belonging to family Umbelliferae, is a native plant of the Mediterranean region and is widely cultivated in India, Russia, Central Europe, Asia, and Morocco. Coriander was widely applied in producing chutneys and sauces, flavoring pastry, cookies, buns, and tobacco products, and extensively employed for preparation of curry powder, pickling spices, sausages, seasonings, and food preservatives [Coriander , were tested [A. baumannii strains both ranged between 1 and 4 \u03bcL/mL. Another study investigated the synergistic antibacterial effects of coriander EO and six antibacterial drugs against two A. baumannii strains [A. baumannii to the action of chloramphenicol. Freires et al. [Candida spp. The results showed that the MICs ranged from 15.6 to 31.2 \u00b5g/mL, and MFCs ranged from 31.2 to 62.5 \u00b5g/mL against Candida spp. for coriander EO. Sliva et al. [B. cereus and E. faecalis. The MICs of coriander against all tested bacteria ranged from 0.1% to 1.6% v/v, and MBCs ranged from 0.1% to 3.2% v/v except B. cereus and E. faecalis. Acimovic et al. [Colletotrichum acutatum and Colletotrichum gloeosporioides using the inverted petriplate method. The results indicated that coriander EOs could inhibit Colletotrichum genus at higher application rates (\u22650.16 \u03bcL/mL of air).Duarte et al. investige tested . The MIC strains . The ress et al. investiga et al. assessedc et al. assessedCurpularia palliscens, F. oxysporum, Fusarium monitiforme, and Aspergillus terreus (A. terreus), and the oleoresin inhibited more than 50% mycelial zones for F. oxysporum, A. niger, and A. terreus. The results of the latter method indicated that EO 100% inhibited the growth of A. terreus, A. niger, F. graminearum, and F. oxysporum, but the oleoresin exhibited weaker fungitoxic activities, which only 100% inhibited the growth of F. oxysporum. In another study, the antimicrobial activities of ethanol and aqueous-ethanol extracts of coriander were investigated against B. subtilis, S. aureus, P. vulgaris, E. coil, P. aeruginosa, K. peunomonia, L. monocytogenes, and C. albicans [P. vulgaris and C. albicans, and was more potent against tested microorganisms. Besides, aqueous-ethanol extract exhibited the highest activities against B. subtilis and L. monocytogenes. Furthermore, the effect of microwaves on EO of coriander on its antimicrobial activities was also tested [Singh et al. reportedalbicans . Ethanolo tested . The antC. albicans [Coriander EO permeated the cell membranes, resulting in the loss of all cellular functions . The mecalbicans .Salmonella sp. Dimic et al. [A. parasiticus, Cladosporium cladosporioides (C. cladosporioides), Eurotium herbariorum, Penicillium chrysogenum, and Aspergillus carbonarius) by the agar dilution method and vapor phase method. The results indicated that coriander extract had the best antifungal activities in the vapor phase as it completely inhibited A. parasiticus, C. cladosporioides, E. herbariorum, and P. chrysogenum at 4.17 \u03bcL/mL.The antimicrobial activities of four spice EOs against isolated clinical specimens were compared using the diffusion method , and thec et al. tested tA. baumannii, Campylobacter spp. at low MICs, MBCs, and MFCs and L. monocytogenes (MIC < 0.625 mg/mL at 24 h and 1.25 mg/mL at 48 h). Moreover, the synergistic antimicrobial effects of extract combination on S. aureus, L. monocytogenes, E. coli, S. typhimurium, and Clostridium perfringens were evaluated [S. aureus and L. monocytogenes, while galangal and lemon iron bark showed synergistic activities against E. coli and S. typhimurium. Additionally, Rao et al. [B. subtilis, E. aerogenes, E. cloacae, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa, S. typhimurium, S. aureus, and S. epidermis using agar well diffusion method and macrodilution method. Among the three solvents used, the activities of methanol extract at pH 5.5 were excellent against all the pathogens . Another study also evaluated the antimicrobial activities of methanol extracts of four Alpinia strains against six strains of bacteria and four strains of fungi, using the disc diffusion assay [M. luteus and only the extract from galangal rhizome showed antifungal activity toward A. niger. The mechanisms of action of galangal have been rarely explored up till now.Galangal has beenn assays . The hexvaluated . Galangao et al. tested ton assay . The resPiper nigrum) to 1250 \u03bcg/mL (E. coli and K. pneumonia).Black pepper ( nigrum) is largeod assay . The resi et al. evaluateE. coli, and then result in the leakage of electrolytes, ATP, proteins, and DNA materials [Black pepper EO could cause physical and morphological alterations in the cell walls and membranes of aterials . ChemicaAllium roseum L., Cinnamomum verum, Laurus nobilis, Myristica fragrans, and Pimpinella anisum\u2014were also proved to possess significant antifungal and antibacterial activities (The antimicrobial activities of the spices mentioned above against several common microorganisms are summarized in tivities .B. subtilis and P. fluorescens; pathogens like S. aureus, V. parahaemolyticus, and S. typhimurium; harmful fungi like A. flavus and A. niger; and even antibiotic resistant microorganisms such as MRSA. Therefore, these spices could be used to decrease the possibility of food poisoning and spoilage, to increase the food safety and shelf-life of products, and to treat some infectious diseases. In the future, as the combinations of several spices were proven to possess higher inhibitory effects on specific bacteria than those of individual spices, the interactions of more spices should be studied and evaluated to inhibit different microorganisms in different food products. Additionally, spices could be used in food packaging as published, but more studies are required to take the other aspects into consideration, such as how to prevent odor/flavor transferring from packages containing natural spice extracts to the packaged foods. Furthermore, spice products may be considered as an alternative to common antibiotics to treat infectious diseases. As the majority of the studies focused on the in vitro activities of spices against human pathogenic bacteria, in vivo studies and clinical trials are needed to be conducted in future. The mechanisms of antimicrobial action of spices remain to be clarified in order to make the best use of spices. Furthermore, the potential toxicity of spices on humans should be evaluated.The antibacterial and antifungal activities of commonly used spices have been summarized. Several spices\u2014such as clove, oregano, thyme, cinnamon, and cumin\u2014have exhibited significant antimicrobial activities against food spoilage bacteria like"} +{"text": "Developmental Psychology, 2018, Vol. 54, No. 1, pp. 167\u2013180. http://dx.doi.org/10.1037/dev0000398), the copyright license has been changed to the Creative Commons CC-BY Attribution License. The online version of this article has been corrected.In the article \u201cPerceived Age Discrimination Across Age in Europe: From an Ageing Society to a Society for All Ages,\u201d by Christopher Bratt, Dominic Abrams, Hannah J. Swift, Christin-Melanie Vauclair, and Sibila Marques ("} +{"text": "Bombax ceiba L. (the red silk cotton tree) is a large deciduous tree that is distributed in tropical and sub-tropical Asia as well as northern Australia. It has great economic and ecological importance, with several applications in industry and traditional medicine in many Asian countries. To facilitate further utilization of this plant resource, we present here the draft genome sequence for B. ceiba.B. ceiba by using PacBio single-molecule sequencing and BioNano optical mapping technologies. The final draft genome is approximately 895 Mb long, with contig and scaffold N50 sizes of 1.0 Mb and 2.06 Mb, respectively.We assembled a relatively intact genome of B. ceiba will be a valuable resource enabling further genetic improvement and more effective use of this tree species.The high-quality draft genome assembly of Bombax ceiba Linn. , commonly known as the cotton tree or red silk cotton tree, is a spectacular flowering tree with a height of up to 40 meters . Genomic DNA was extracted from leaves of a single tree using the Plant Genomic DNA kit . A SMRTbell DNA library was then prepared and sequenced using P6, C4 chemistry according to the manufacturer's protocols , and a 20-kb SMRTbell library was generated using a BluePippin DNA size selection instrument with a lower size limit of 10 kb. Single-molecule real-time sequencing of long reads was conducted on a PacBio Sequel platform with 19 SMRT cells. A total of 86.0 Gb of genomic data with an average read length of 8.4 kbwas generated after quality filtering . In addiB. ceiba individual using the QIAGEN RNeasy Plant Mini Kit . RNA-seq libraries were then prepared using the TruSeq RNA Library Preparation Kit , and paired-end sequencing with a read length of 150 bp was conducted on the HiSeq 2000 platform, yielding 44.41 Gb of clean data .B. ceiba was estimated by the K-mer method [B. ceiba genome was approximately 0.88%.The genome size of r method using ser method . The couTheobroma cacao and Gossypium species, comprising more than 69% of the hits were detected . Samples were then loaded into IrysChips and imaged on an Irys imaging instrument . After filtering using a molecule length cutoff of <150kb, a molecule SNR of <2.75, a label SNR of <2.75, and a label intensity of >0.8, 160.0 Gb of BioNano clean data were obtained, with the N50 size of the labeled single molecules being 269.9 kb [RRID:SCR_010910) to fill the gaps and correct potential sequencing errors of the assembly, and a mapping rate of 99.2% was achieved [To fill the gaps in the scaffolds, the Blasr pipline was used_012091) over thrachieved . The finachieved , yieldinB. ceiba genome assembly using HISAT [RRID:SCR_015008) [To evaluate the coverage of the assembly, we aligned all the RNA-seq reads against the ng HISAT with def_015008) to searcB. ceiba genome, with default parameters. A total of 454,435 SSRs were identified in this way: 310,369, 105,004, 30,925, 6,448, 1,165,and 524 mono-, di-, tri-, tetra-, penta-, and hexa-nucleotide repeats, respectively (The repeat sequences in the genome consisted of simple sequence repeats (SSRs), moderately repetitive sequences, and highly repetitive sequences. The MISA tool was usedectively .B. ceiba genome, RepeatMasker [de novo evolved annotation was performed using RepeatModeler v. 1.0.11 [de novo predictions indicated that repeated sequences account for 60.30% of the B. ceiba genome assembly (To identify known transposable elements (TEs) in the _012954) was used_012954) and Mips_012954) . In addi_015027) . The comassembly , with loassembly .B. ceiba genome using BLASTN [RRID:SCR_010835) [Homology-based ncRNA annotation was performed by mapping plant rRNA, miRNA, and snRNA genes from the Rfam database (release 13.0) to the Bg BLASTN was used_010835) was usedde novo predictions were also used to annotate protein coding genes. For homology-based predictions, protein sequences from four species [de novo predictions, we first randomly selected 1,000 full-length genes from the homology-based predictions to train model parameters for Augustus v3.0 [RRID:SCR_002654) [The homology-based and . cacao) were map_015054) to searc_008417) , GeneID _008417) , Glimmer_002654) , and SNA_002654) . Augustu_002654) , GeneID _002654) , Glimmer_002654) , and SNA_002654) were the_002654) was used_002654) package.B. ceiba were screened for homology against the Uniprot (release 2017_10) and KEGG (release 84.0) databases using Blastall [RRID:SCR_005829) [The annotations of the predicted genes of Blastall and KAASBlastall . Then, t_005829) package B. ceiba, we compared its genome to the genome sequences of 12 other plants. These included four plants in the Malvales order , seven plants from different orders in the same Eudicots clade , and Oryza sativa as an outgroup. Genome sequences from A. thaliana, T. cacao, C. papaya, L. usitatissimum, P. trichocarpa, C. sinensis, S. lycopersicum, V. vinifera, and O. sativa were downloaded from Phytozome v. 12.0 [G. arboreum, C. olitorius, and D. zibethinus were downloaded from the NCBI Database . We used the OrthoMCL (v2.0.9) pipeline [B. ceiba [RRID:SCR_006086) v 8.2.11 [RRID:SCR_014932) [B. ceiba from the other plants. The parameter settings of MCMCTREE were as follows: clock = 2, RootAge \u2264 1.73, model = 7, BDparas = 110, kappa_gamma = 62, alpha_gamma = 11, rgene_gamma = 23.18, and sigma2_gamma = 14.5. In addition, the divergence times of O. sativa (148\u2013173 Mya), V. vinifera (110\u2013124 Mya),and A. thaliana (53\u201382 Mya) were used for fossil calibration. The phylogenetic analysis showed that B. ceiba is more closely related to G. arboraum than to D. zibethinus and cura_011812) . Phylogev 8.2.11 with the_014932) to estimbethinus , which sMya Fig. .B. ceiba is an ecologically important plant that could survive in extreme climate conditions, such as hot-dry valleys [B. ceiba lineage. These genes might contribute to the adaption to unfavorable environments. Thirty-six genes with signatures of positive selection were identified (P \u2264 0.05), of which 32 genes could be annotated with potential functions in the Swissport database (Lea14). There is a strong association of LEA proteins with abiotic stress tolerance, particularly during dehydration and cold stress [B. ceiba to the dry valley environment. Another gene showing signs of positive selection is homologous to the gene coding for Kelch domain-containing protein 4. The Kelch domain-containing proteins are involved in regulating major processes such as growth, development, and biotic and abiotic stress responses in plants [B. ceiba. It should be noted that this is just a preliminary analysis of the functions of these genes; further studies would be needed to clarify their roles. valleys . Accordi valleys , the rat valleys to identdatabase . One gend stress . This gen plants , 48. Somn plants , 50. Twen plants . While lB. ceiba genome. To this end, paralogous sequences of B. ceiba, T. cacao, V. vinfira, S. lycopersicum, and D. zibethinus was identified with OrthoMCL [B. ceiba experienced the same WGD events as other Dicotyledons, and that B. ceiba and D. zibethinus went through their WGD events before diverging from their common ancestor database of National Center for Biotechnology Information with Bioproject ID PRJNA429932. The assembly and annotation of the , GigaDB . VersionFigure S1. Frequency distribution of the 17-mer graph analysis used to estimate the size of the B. ceiba genome.Figure S2. GC content distribution of the B. ceiba genome. The GC content was established using 500-bp slidingwindows.Figure S3. The GC depth distribution of the B. ceiba genome.Figure S4. Comparison of gene structure characteristics in B. ceiba to that in other plants. a, CDS length; b, exon length; c, exon number; d, gene length; e, intron length.Figure S5. Gene orthology determined by comparing genomes using the OrthoMCL software.Figure S6. The maximum-likelihood phylogeny of B. ceiba and 13 other plants.Figure S7. Gene family expansions and contractions in B. ceiba and 13 other plants.Table S1. Sequencing statistics from the PacBio platform.Table S2. Summary of the transcriptomes and their mapping rates on the genome assembly.Table S3. Estimation of genome size based on 17-mer statistics.Table S4. Blast results of B. ceiba genome against the NCBI Nt database.Table S5. Summary of the BioNano optical mapping data.Table S6. Summary of the final genome assembly.Table S7. Summary of BUSCO analysis results.Table S8. Summary of the SSR search results.Table S9. Repeat annotation of the B. ceiba genome assembly.Table S10. Summary of non-protein-coding gene annotations in the B. ceiba genome assembly.Table S11. Gene annotation statistics of the B. ceiba genome assembly.Table S12. Comparative gene statistics.Table S13. Functional annotation of predicted genes of B. ceiba.Table S14. Summary statistics of gene families in 13 plant species.Table S15. Candidate positively selected genes in the B. ceiba lineage.Table S16. Versions and main parameters of the software used in this study.SMRT: single molecule real time; 4DTv: four-fold synonymous third-codon transversion.S.S. is an employee of Nextomics Bioscences. Other authors declare that they have no competing interests.L.T. and B.T. designed the project; H.W., C.L., and H.C. collected samples and extracted the DNA and RNA samples; Y.G., S.S., H.,W. and C.L. worked on sequencing and data analyzing; Y.G. wrote the manuscript; L.T., B.T., and D.D. revised the manuscript; Y. G., H. W., C. L., H. C., D. D., S. S., L. Y., L. H., Y. F., B. T. and L. T. read and approved the final version of the manuscript.GIGA-D-18-00045_Original_Submission.pdfClick here for additional data file.GIGA-D-18-00045_Revision_1.pdfClick here for additional data file.GIGA-D-18-00045_Revision_2.pdfClick here for additional data file.Response_to_Reviewer_Comments_Original_Submission.pdfClick here for additional data file.Response_to_Reviewer_Comments_Revision_1.pdfClick here for additional data file.Reviewer_1_Report_ -- Nicolas Delhomme, Ph. D. rer. nat.2/23/2018 ReviewedClick here for additional data file.Reviewer_2_Report_ -- Yuxuan Yuan2/27/2018 ReviewedClick here for additional data file.Reviewer_2_Report_(Revision_1) -- Yuxuan Yuan3/19/2018 ReviewedClick here for additional data file.Reviewer_2_Report_(Revision_2) -- Yuxuan Yuan4/8/2018 ReviewedClick here for additional data file.Supplemental materialClick here for additional data file."} +{"text": "Scientific Reports5: Article number: 16055; 10.1038/srep16055 published online: 11042015; updated: 01192017.The original version of this Article contained a typographical error in Reference 24, which was incorrectly given as:T. Tufarelli, K. R. McEnery, S. A. Maier & M. S. Kim. Phys. Rev. A 89, 023817 (2014).This has been corrected in the HTML and PDF versions of this Article."} +{"text": "Leptocybe invasa Fisher & La Salle is an invasive pest in Eucalyptus plantations throughout the world. Potential biological control agents for L. invasa were investigated in the Fujian, Guangdong, Hainan, Guangxi, Jiangxi, and Sichuan provinces of China, where Eucalyptus spp. have been severely damaged by the eucalyptus gall wasp. Three hymenopteran parasitoids of L. invasa were identified: Quadrastichus mendeli Kim & La Salle (Eulophidae), Aprostocetus causalis La Salle & Wu (Eulophidae), and Megastigmus viggianii Narendran & Sureshan (Torymidae); M. viggianii is newly recorded in China. The percentages of parasitization by Q. mendeli, A. causalis, and M. viggianii were 2.96%\u201319.53%, 2.30%\u201326.38%, and 24.93%, respectively. The longevity and body length of females were significantly greater than for males in A. causalis and M. viggianii. No males of Q. mendeli were found in China. These parasitoids could be used as biological agents for L. invasa in China. Eucalyptus is one of the three major fast-growing tree species worldwide, which plays important roles in reforestation and the production of timber, pulp, potential bioenergy feedstock, and other forest products . In ChinLeptocybe invasa Fisher & La Salle (Hymenoptera: Eulophidae), originating from Australia, is a global pest in Eucalyptus plantations [L. invasa populations and the existence of different putative species, among them a \u201cChinese lineage\u201d [L. invasa. Leptocybe invasa has expanded to more than 29 countries in Asia, Europe, Africa, and the Americas [L. invasa was first found in the Guangxi Zhuang Autonomous Region in April 2007 [L. invasa, including chemical control [The eucalyptus gall wasp, ntations . A recenlineage\u201d . The wasAmericas , 35. In ril 2007 . Subsequril 2007 , 34. Var control , breedin control , 16. HowL. invasa [L. invasa parasitoids have been found in the invaded regions, e.g., India, Israel, Turkey, Italy, Sri Lanka, Thailand, Argentina, and South Africa [L. invasa are different in these regions. Thus far, only Aprostocetus causalis La Salle & Wu (Hymenoptera: Eulophidae) and Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae) have been reported to parasitize L. invasa in the Guangxi and Hainan provinces of China [L. invasa and their parasitic capacities in the field are unknown. Therefore, it is necessary to widely investigate biological control agents for L. invasa in China.In Australia, parasitoids play a very important role in limiting the populations of . invasa , 15. The. invasa . However. invasa . Recentlh Africa \u201315, 21. of China , 17, 32.L. invasa occurring on Eucalyptus spp. In this study, we investigated the species of parasitoids present in some Chinese regions.The purpose of this study was to identify possible biological control agents for Eucalyptus grandis\u00a0\u00d7\u00a0E. tereticornis) , E. tereticornis Smith, E. Exserta L., and E. grandis\u00a0\u00d7\u00a0E. urophylla damaged by L. invasa were collected from Fujian, Guangdong, Hainan, Guangxi, Jiangxi, and Sichuan provinces from 2015 to 2016. The sampling sites and sampling times for each province are shown in L. invasa and their parasitoids.Eucalyptus gall wasps were searched for by the typical bump-shaped galls they form on leaf midribs, petioles, and stems . BrancheL. invasa adults . Images of the parasitoid adults were taken with a Sony digital camera . Identification of the parasitoids was performed with keys , 15, 32 U test. The results were considered significant at p\u00a0\u2264\u00a00.05.Statistical analysis was performed using SPSS 16.0 . Adult longevities and body lengths were compared using the nonparametric Mann-Whitney L. invasa collected from Fujian, Guangdong, Hainan, Guangxi, Jiangxi, and Sichuan provinces: Q. mendeli, A. causalis, and Megastigmus viggianii Narendran & Sureshan (Hymenoptera: Torymidae); M. viggianii is newly recorded in China and body length of A. causalis females were significantly greater than for males .Quadrastichus mendeli is one of the indigenous parasitoids parasitizing L. invasa in Australia [Q. mendeli was introduced from Australia to Israel and India as a biological control agent to limit the severity of damage caused by L. invasa. The parasitoid is now successfully established in Israel and India, and the percentage of parasitization was 73% in Israel and 81.74\u201394.03% in India [Q. mendeli population in quarantine facilities in South Africa and Kenya have failed [Q. mendeli was collected from L. invasa galls on E. Camaldulensis Dehnh. in Italy beginning in 2013, although this parasitoid was never officially released [Q. mendeli varied from 30.2% to 50.5% in Italy [Q. mendeli parasitizing L. invasa in China under natural conditions, although this parasitoid was never officially released in China. Although Q. mendeli is a widely distributed L. invasa parasitoid in China, the percentage of parasitization differed in these geographical populations in India [L. invasa larvae for the first time in India [M. viggianii was only found in the Sichuan site; thus, we cannot ascertain whether this parasitoid is native to China. Furthermore, M. viggianii has a multi-host-range compared to Q. mendeli and A. causalis. Other M. viggianii hosts have not been found in China and need further investigation.in India . In 2008in India , and thein India . HoweverL. invasa in China with possible competition for the monopolization of host resources. The percentage of parasitization by Q. mendeli was always higher than that by A. causalis when the two parasitoids attacked the eucalyptus gall wasp in Guangdong, Hainan, and Guangxi provinces. However, the percentage of parasitization by Q. mendeli was lower than those for A. causalis and M. viggianii when the three parasitoids attacked eucalyptus gall wasps in Sichuan province. We presumed that this could be attributed to the population dynamics of Q. mendeli in Sichuan province, but this needs to be confirmed. Previous studies showed that Q. mendeli is a solitary idiobiont ectoparasitoid [A. causalis and M. viggianii are solitary koinobiont endoparasitoids [Q. mendeli) and endoparasitoids in L. invasa need to be studied.In the field, two or three parasitoids attacked rasitoid while A.asitoids . The comOphelimus maskelli Ashmead (Hymenoptera: Eulophidae) is a leaf-gall-inducing invasive pest of several Eucalyptus species in California, while its parasitoid, Closterocerus chamaeleon Girault (Hymenoptera: Eulophidae), was also found less than 1\u00a0year after Q. maskelli [Q. mendeli and M. viggianii were never released in China, their record leads us to suppose that they could shortly reach other neighboring countries around China.In general, parasitoids have host-tracked their hosts either simultaneously or following invasion by the pest. For example, maskelli . As Q. mQ. mendeli, A. causalis, and M. viggianii could be used as biological control agents for L. invasa in China. However, further studies are needed on the biological characteristics, mass production and release, competitive dynamics and mechanisms of these parasitoids.In this study, we found that The authors declare no conflict of interest in relation with this paper."} +{"text": "Scientific Reports 10.1038/s41598-017-16052-7, published online 16 November 2017Correction to: The original version of this Article contained a typographical error in the spelling of the author T. Joshua Pfefer, which was incorrectly given as Joshua Pfefer.Additionally, the Author Contributions section in this Article was incomplete.\u201cA.F. performed all experiments and simulations and wrote the initial draft of this manuscript. W.V., J.P. and I.I. provided guidance and feedback throughout the study. All authors edited and reviewed the manuscript.\u201dnow reads:\u201cA.M.F. performed all experiments and simulations and wrote the initial draft of this manuscript. W.C.V., T.J.P. and I.K.I. provided guidance and feedback throughout the study. All authors edited and reviewed the manuscript. T.J.P and I.K.I conceived and planned the study.\u201dThese errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information."} +{"text": "Prentice, M. B., Bowman, J., Lalor, J. L., McKay, M. M., Thomson, L. A., Watt, C. M., \u2026 Wilson, P. J. (2017). Signatures of selection in mammalian clock genes with coding trinucleotide repeats: implications for studying the genomics of high\u2010pace adaptation. Ecology and Evolution, 7, 7254\u20137276Figure 8 was mistakenly published with the top right\u2010hand panel duplicated in the bottom right corner of the figure, in place of the correct panel. In this corrigendum, the bottom right\u2010hand panel has been replaced with the correct panel."} +{"text": "Scientific Reports7: Article number: 4014710.1038/srep40147; published online: 03152017; updated: 05172018In the original version of this Article, the author L. C. C. Dennis was inadvertently omitted from the Author Contributions statement and the Supplementary Information.The Author Contributions statement,\u201cI.K. formulated the problem N.A.S. solved the problem and prepared the figures. I.K. and N.A.S. wrote the main manuscript text. Both authors reviewed the manuscript.\u201dnow reads:\u201cI.K. formulated the problem. N.A.S. solved the problem. L. C. C. Dennis performed the numerical simulations and prepared the results. I.K. and N.A.S. wrote the physical discussion of the figures. I.K, and N.A.S wrote main manuscript text. L. C. C. Dennis proof read the manuscript.\u201dIn addition, the Acknowledgements section was omitted and now reads:\u201cThe authors acknowledge with thanks the Deanship of Scientific Research (DSR) at Majmaah University, Majmaah Saudi Arabia for technical and financial support through vote number 37/97 for this research project.\u201dThese errors have now been corrected in the HTML and PDF versions of the Article, and in the accompanying Supplementary Information."} +{"text": "Ovis aries) are intermediate hosts for at least six named species of Sarcocystis: S. tenella, S. arieticanis, S. gigantea, S. medusiformis, S. mihoensis, and S. microps. Here, only two species, S. tenella and S. arieticanis, were found in 79 of 86 sheep (91.9%) in Kunming, China, based on their morphological characteristics. Four genetic markers, i.e., 18S rRNA gene, 28S rRNA gene, mitochondrial cox1 gene, and ITS-1 region, were sequenced and characterized for the two species of Sarcocystis. Sequences of the three former markers for S. tenella shared high identities with those of S. capracanis in goats, i.e., 99.0%, 98.3%, and 93.6%, respectively; the same three marker sequences of S. arieticanis shared high identities with those of S. hircicanis in goats, i.e., 98.5%, 96.5%, and 92.5%, respectively. No sequences in GenBank were found to significantly resemble the ITS-1 regions of S. tenella and S. arieticanis. Identities of the four genetic markers for S. tenella and S. arieticanis were 96.3%, 95.4%, 82.5%, and 66.2%, respectively.Sheep ( Sarcocystis spp. are cyst-forming intracellular protozoan parasites with an obligate two-host life cycle between predators as definitive hosts and prey animals as intermediate hosts. Sheep (Ovis aries) are intermediate hosts for at least six species, i.e., S. tenella, S. arieticanis, S. gigantea, S. medusiformis, S. mihoensis, and S. microps, which are morphologically differentiated based on their sarcocyst wall ultrastructure. Sarcocystis tenella and S. arieticanis produce microscopic sarcocysts transmitted by canids, while S. gigantea and S. medusiformis produce macroscopic cysts transmitted by felids . trusions . Sarcocymusimon) and Sarcin goats , S. hircschatus) , plus S.Sarcocystis spp. are not very clear. It is not easy to complete cross-transmission for Sarcocystis spp. using large experimental animals in the laboratory. Accordingly, characterizing sequences of different genetic markers should be a useful tool to differentiate these species of Sarcocystis or delineate their phylogenetic relationships. For example, Sarcocystis sp. in chamois has been designated as S. tenella based on the similarities of their 18S rRNA and cox1 sequences [Thus, the two sarcocyst TEM types (14 and 7) in domestic sheep are common in the tissues of different, but closely related, ruminant animals; however, the relationships between these morphologically similar equences .18S rRNA, 28S rRNA, cox1, and ITS-1) for Sarcocystis spp. in sheep were sequenced and characterized. Among them, sequences of cox1 for S. arieticanis and ITS-1 for Sarcocystis spp. in sheep were the first records in GenBank. When blasting these sequences in GenBank, sequences of 18S rRNA, 28S rRNA, and cox1 for S. tenella shared high identities with those of S. capracanis, i.e., 99.0%, 98.3%, and 93.6%, respectively; S. hircicanis shared high identities with S. arieticanis, i.e., 98.5%, 96.5%, and 92.5%, respectively. Therefore, mitochondrial cox1 seemed to perform better than 18S rRNA and 28S rRNA for distinguishing S. tenella from S. capracanis, and S. arieticanis from S. hircicanis. The high identity (99.0%) between 18S rRNA sequences for S. tenella and S. capracanis has even led to a debate whether sheep and goat can harbor the same Sarcocystis species [ITS-1 regions of S. tenella and S. arieticanis. However, when comparing the new sequences of the four genetic markers for S. tenella and S. arieticanis, the sequence identities were 96.3%, 95.4%, 82.5%, and 66.2%, respectively. Thus, the ITS-1 region could be more useful for discriminating closely related Sarcocystis spp. because of its high divergence.In the present study, four genetic markers ("} +{"text": "Journal of Experimental Psychology: Animal Learning and Cognition, 2017, Vol. 43, No. 2, pp. 159\u2013170. http://dx.doi.org/10.1037/xan0000134) was incorrectly published under American Psychological Association copyright. The authors should have retained copyright of this article under the Creative Commons Attribution License. The online version of this article has been corrected.The article \u201cFamiliarity-Based Stimulus Generalization of Conditioned Suppression\u201d by Jasper Robinson, Emma J. Whitt, and Peter M. Jones ("} +{"text": "Scientific Reports7: Article number: 42681; 10.1038/srep42681 published online: 02162017; updated: 04102017.The original version of this Article contained a typographical error in the spelling of the author Laura Medina-Ruiz, which was incorrectly given as Laura Medina Ruiz. This has now been corrected in the PDF and HTML versions of the Article.The Author Contributions statement now reads:D.P.D., K.P., L.M-R., F.S. and G.W. performed experiments. G.J.G. conceived the study. G.J.G. and D.P.D. wrote the manuscript. All authors approved the manuscript prior to submission."} +{"text": "All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort\u00a0still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of\u00a0age.The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project maintained optimal growth and development in childhood.The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites.In the Infant Follow-up Study of the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% . An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions.There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards.The cohort enrolled in the INTERGROWTH-21 Although human growth, from cell\u00a0to whole body, is recognized as\u00a0a universal biologic process, some entrenched views persist regarding fetal growth, in particular that it should be compared with a site-specific rather than\u00a0prescriptive population. This view is\u00a0not held by the World Health Organization (WHO) or by the Centers for Disease Control & Prevention,We have summarized the key statistical, physiologic, ethnic, and genetic evidence relating to this issue.This neglected aspect of obstetric practice means that clinical decisions are\u00a0made based on reference charts that were derived from a wide range of different study populations. For example, a woman may have an early gestational age assessment with the use of a fetal crown-rump length chart based on a study of 80 women from Glasgow, Scotland,If the woman requires further assessment, the umbilical Doppler measures are\u00a0judged with the use of yet another reference population.st Project aimed to resolve these issues by conducting studies of human growth and development that involved pregnant women who were enrolled at <14 weeks gestation specifically to monitor their fetuses, newborn infants, and children prospectively up to 2 years of age to generate a single set of international standards to make judgements on the growth of all humans.The INTERGROWTH-21st Standards are prescriptive because they are based on a cohort of \u201chealthy\u201d pregnancies and babies from the same geographically selected populations in which most of the health and nutritional needs of mothers were met and adequate antenatal care provided.Hence, the INTERGROWTH-21st babies represent true standard populations.Nevertheless, the question always remains with studies that are focused on fetal growth as to how \u201chealthy\u201d were these children after birth and during childhood . We took this question seriously very early in the planning of the project and added a clinical and developmental follow-up evaluationst Standardsst Project.Hence, we first compared the INTERGROWTH-21This study aimed to evaluate the growth, nutrition, morbidity, and motor development at 2 years of age of the infants who were included in the international fetal and preterm growth standards to reinforce their prescriptive nature against which fetuses and preterm\u00a0infants worldwide can now be compared.st was a multicenter, population-based project that was conducted between 2009 and 2016 in 8 locations: Pelotas, Brazil; Turin, Italy; Muscat, Oman; Oxford, UK; Seattle, WA; Shunyi County, Beijing, China; the central area of Nagpur, India, and the\u00a0Parklands suburb of Nairobi, Kenya.24INTERGROWTH-21st Project,The primary aim of the project was to study growth, health, nutrition, and neurodevelopment from <14 weeks gestation to 2 years of age.+0 to 13+6 weeks gestation with the use of a standard protocol. All fetuses in the Fetal Growth Longitudinal Study were eligible to contribute data to the construction of the international fetal growth standards; all infants who were born at <37 weeks gestation in the Fetal Growth Longitudinal Study were eligible to contribute data to the construction of the international Postnatal Growth Standards for Preterm Infants. At each postnatal visit, a record of any illnesses in the preceding months was noted in addition to anthropometric measurements and a developmental assessment.Gestational age was estimated based on the date of the last menstrual period and corroborated by ultrasound measurement of crown-rump length at 9st Project.Weight, length, and head circumference were obtained within 12 hours (and\u00a0no >24 hours) of birth on the postnatal wards and at follow-up visits that were scheduled at 1 and 2 years of age (\u00b11\u00a0month). Measurements were taken exclusively by the same teams who were trained and standardized at regular intervals for the INTERGROWTH-21All study sites used the same methods and equipment: electronic scales for weight (sensitivity of 10 g to 20 Kg); a specially designed Harpenden infantometer for recumbent length, and a metallic nonextendable tape (Chasmors Ltd) for head circumference.Measurements were taken twice, independently, by 2 of the study anthropometrists. If the difference between the\u00a02\u00a0measures exceeded for weight 50 g for newborn infants and \u2264100 g at 1 and 2\u00a0years of age , then both observers independently repeated that measurement a second time and, if necessary, a third time.27When the Infant Follow-up Study started, some enrolled children had passed their second birthday already. The families of these children were invited to a follow-up visit with the maximum age at assessment for the child being 27 months. Similarly, those children who already had passed their first birthday, but were <2 years old, were invited initially for the first visit up to the age of 18 months. In total, only 14% of 1- and 2-year visits occurred outside the protocol-designated age range for assessment.www.intergrowth21.org).Detailed information was obtained from the mother about the infant\u2019s health, severe morbidities, length of breastfeeding, timing of the introduction of food, feeding practices, and food intake with the use of standardized forms that were produced especially for the project (http://www.intergrowth21.org.uk).WHO protocols were followed to assess motor development milestones.We collected the same information from parents at 1 and 2 years of age to evaluate the consistency of the reported dates. There were 7965 pairs of values recorded at year 1 and the year 2 interviews, of which 92.6% were identical at both visits. Among the 588 discrepant values, the median difference ranged between \u20131 week for hands and knees crawling to \u20130.2 weeks for standing alone. In these cases, after investigation, the values that were obtained at the 1-year visit were used.st Neonatal Group (http://www.intergrowth21.org.uk).34Across all study sites, standardized clinical care and feeding practices were\u00a0implemented based on protocols that were developed by the INTERGROWTH-21Age- and sex-specific z-scores and percentiles were estimated for each child at 2 years of age comparing their weight, length, and head circumference to the WHO Child Growth Standards.Variance components analysis was performed to calculate the percentage of variance in infant length at birth, 1, and 2 years because of between- and within-site variance. A multilevel mixed effects model was fitted with random intercepts for the study site and individual levels . The model, which was fitted with unstructured covariance structure, was adjusted by age and sex. Both age and sex were treated as fixed effects.We analyzed 2026 mother-father-infant trios to compare the \u201cmean parental height\u201d with a predicted adult height for each infant, defined as twice their length at 2 years of age.For infants reported to have achieved the milestones, the proportions within the\u00a0WHO motor development windows of achievementThe proportion of infants who received breast milk and vitamin and mineral supplements and those who followed a special diet were estimated at 1 and 2 years of age.39http://medscinet.com).We used Stata software . Data were entered locally into the specially developed online data management system (st Project was approved by the Oxfordshire Research Ethics Committee \u201cC\u201d (reference: 08/H0606/139), the research ethics committees of the individual institutions, and the regional health authorities where the project was implemented. Participants provided written consent to be involved in the study.The INTERGROWTH-21st fetal growth standards.There were 4321 singleton newborn infants who were alive at birth without congenital malformations whose mothers were recruited at <14 weeks gestation and included in the cohort of the international INTERGROWTH-21The means (\u00b1SD) of the age at which measures were obtained were 24.4\u00b11.2 and 23.2\u00b10.7 months for the total cohort and the preterm subgroup, respectively; 86% of the 2-year measures were obtained from 23\u201325 months for the total cohort and 93% were obtained for the preterm subgroup.The neonatal characteristics of the infants divided into those that completed the 2-year follow-up evaluations (n=3042) and those lost to follow up (n=669) are presented in At hospital discharge, 89% of the total cohort and 74% of the preterm subgroup were exclusively breast-milk fed. Similar patterns were seen among the children who were lost to follow-up at 2 years of age. Exclusive breastfeeding was stopped at a median of 5 months ; this was similar in the preterm subgroup. Breastfeeding stopped entirely at a median of 12 months for the total cohort and 11 months for the preterm subgroup.In the total cohort, the proportion of children who still were receiving breast milk fell from 59% at 1 year to 11% at 2 years, by which time 34% of the children were formula fed. All children received dairy products of some type (including human milk) at both ages. Food supplements had been given routinely to 33% of children by 1\u00a0year and 21% by 2 years. At 1 year of age, 51% of the infants in the preterm subgroup were still receiving breast milk; the figure fell to 8% at 2 years, by which time 34% of children were\u00a0receiving formula. Food supplements that included vitamins and minerals were given to 36% of the infants in the first year and 28% of the infants by the second year in the preterm cohort. Complementary feeding practices were considered appropriate in terms of diversity, the timing of introduction, and the food variety across sites and 2.34The overall morbidity rate in the total cohort was low ; only 9%At 1 year of age, a comparison of the total cohort with the age- and sex-specific WHO Child Growth Standards showed that length and head circumference had a mean \u00b1 SD z-score of 0.0\u00b11.1 for both measures and that the medians were at the 49th and 48th percentiles of the WHO Child Growth Standards, respectively; for weight, the mean z-score was 0.2\u00b11.1 and median at the 58th percentile.st Fetal Growth Standards plotted almost perfectly onto the WHO Child Growth Standards .st Project were selected during early pregnancy specifically to generate international standards.st participants, corroborate that they conformed to the WHO prescriptive approach for the construction of human growth standards. They are a cohort with continuous very low rates of clinical conditions that could affect optimal growth and development.The participants included in the construction of the Fetal Growth Standards, the Newborn Size at Birth and the Preterm Postnatal Growth Standards of the INTERGROWTH-21Our findings reinforce the a priori concept23As far as we are aware, this is the first time that a fetal cohort that has been included in longitudinal studies for the specific purpose of constructing prescriptive growth standards has been evaluated up to 2 years of age. Most ultrasound studies that aimed to create reference charts for fetal growth have not reported any postnatal assessment, nor is it likely that such an assessment has been carried out, given the time that has elapsed since these studies were conducted.st standards that complement the WHO Child Growth Standards in postnatal life. The similarities between the INTERGROWTH-21st and WHO studies mean that the size of children, measured at 2 years of age, who were born to healthy mothers, with adequate nutrition, from healthy populations at low risk of adverse pregnancy outcomes, is consistent between the studies and across time.Our unique data are derived from a prospective follow-up evaluation of individuals from 7 different regions of the world from the first trimester of pregnancy to 2 years of age. These findings strengthen the case for the worldwide use of the international INTERGROWTH-21Other strong features of the study include careful standardization of the outcome measures and the comprehensiveness of the standardized clinical and developmental assessments at 2 years of age.We acknowledge some limitations that relate to practical difficulties of carrying out such a large, multicenter study.First, the information on morbidity refers mostly to substantive clinical episodes, and data on gross motor development were obtained from parental report rather than direct observation; however, we informed parents about the Infant Follow-up Study protocol at enrolment and asked them to record severe conditions and infant developmental milestones. In addition, parents were encouraged to bring sick children for care to the participating centers; illness therefore was recorded at the time of the event.Second, the study outcomes do not extend >2 years of age. This juncture was selected because it is a key time for the detection of postnatal growth faltering,st Study, which is the extension to the INTERGROWTH-21st Project.The WHO motor development assessment is a simple, pragmatic, and reliable tool to describe normal variation in the achievement of milestones that are reached progressively across infancy. It is especially recommended for studying a large number of infants at the cohort level, rather than individual level.st publications, we have emphasized that the relevant question when comparing growth across populations is whether the variability in skeletal growth within a population is larger than the variability among populations (interpopulation genetic difference) when nutritional and health needs are met.In all the INTERGROWTH-21We have used variance components analysis in cohorts that were followed prospectively to identify the proportional contribution of the within and between sites variance components.This clinical/epidemiologic finding is of great biologic interest because it is consistent with a metaanalysis of 22 genome-wide association studies that showed that the polygenic scores, based on 180 single nucleotide polymorphisms that previously were associated with adult height, explained only a very small proportion of the total variance in birth and infant length .Our 2-year follow-up evaluation of this large cohort of healthy children allowed their mean predicted adult height to be estimated based on the assumption that health, nutritional, and socioeconomic conditions would remain adequate . Thus, tst Study.Our results confirm a pattern and magnitude of apparent transgenerational \u201cwashout\u201dThe observation that this healthy cohort was at the 58th percentile of the sex-specific weight for age of the WHO Child Growth Standards at 2 years of age has potential implications in describing the natural history of becoming overweight among healthy infants. Because we did not implement any specific nutritional intervention, other than to promote breastfeeding, this weight distribution may represent the initial stages of the overweight epidemic facing many urban children who are exposed to westernized diets. Recent standardized, prospectively collected, fetal data have confirmed the complex effect of nutrition, the environment, migration, and social-cultural issues on fetal growth patterns.50The short-term shift in weight distribution in an otherwise healthy population that we have described also reinforces the concept that comparisons among populations to evaluate growth potential should be based on length rather than weight because of its sensitivity to acute influences.st Study.A larger question that goes beyond the scope of this article relates to the timing, velocity, and individual tracking of growth from conception to 2 years of age vis-\u00e0-vis feeding and morbidity in high-risk populations. The exploration of these questions in a longitudinal fashion, including interactions, has considerable statistical complexity, which we are presently investigating in the INTERBIO-21st Project and who were selected based on the WHO prescriptive approach for growth standards remain healthy and have adequate growth and development patterns at the key milestone of 2 years of age. This is additional strong confirmation of the sample\u2019s appropriateness for the construction of international growth standards. The INTERGROWTH-21st international standards are freely available (www.intergrowth21.tghn.org) for use worldwide.In summary, we have presented evidence that the participants who are enrolled in the international Fetal Growth Standards and the Preterm Postnatal Growth Standards of the INTERGROWTH-21st Project. J.V., S.H.K., D.G.A., and A.J.N. prepared the original protocol, with later input from A.T.P., L.C.I., F.C.B., and ZAB. J.V., A.T.P., L.C.I., A.L., and Z.A.B. supervised and coordinated the project\u2019s overall undertaking. E.S.U., E.O.O., and D.G.A. carried out data management and analysis in collaboration with J.V. R.P., F.C.B., R.O., Y.A.J., E.B., and M.P. collaborated in the overall project and implemented it in their respective countries. F.G. assisted in the global coordination of the project; L.C.I. and C.C. led the quality control of the anthropometric component, and M.F. and A.S. led the neurodevelopment assessment component. J.V. and S.K. wrote the report with significant contributions by F.G., C.G., C.G.V., F.C.B., and Z.A.B. All coauthors read the report and made suggestions on its content.J.V. and S.H.K. conceptualized and designed the INTERGROWTH-21Scientific Advisory Committee: M. Katz (Chair from January 2011), M.K. Bhan, C. Garza, S. Zaidi, A. Langer, P.M. Rothwell (from February 2011), Sir D.\u00a0Weatherall (Chair until December 2010).Steering Committee: Z.A. Bhutta (Chair), J. Villar , S. Kennedy (Project Director), D.G. Altman, F.C. Barros, E. Bertino, F. Burton, M. Carvalho, L. Cheikh Ismail, W.C. Chumlea, M.G. Gravett, Y.A. Jaffer, A. Lambert, P. Lumbiganon, J.A. Noble, R.Y. Pang, A.T. Papageorghiou, M.\u00a0Purwar, J. Rivera, C. Victora.Executive Committee: J. Villar (Chair), D.G. Altman, Z.A. Bhutta, L. Cheikh Ismail, S. Kennedy, A. Lambert, J.A. Noble, A.T. Papageorghiou.Project Coordinating Unit: J. Villar (Head), S. Kennedy, L. Cheikh Ismail, A. Lambert, A.T. Papageorghiou, M. Shorten, L. Hoch (until May 2011), H.E. Knight (until August 2011), E.O. Ohuma (from September 2010), C. Cosgrove (from July 2011), I. Blakey (from March 2011).Data Analysis Group: D.G. Altman (Head), E.O. Ohuma, E. Staines Urias (from April 2016), J. Villar.Data Management Group: D.G. Altman (Head), F. Roseman, N Kunnawar, S.H. Gu, J.H. Wang, M.H. Wu, M.\u00a0Domingues, P. Gilli, L. Juodvirsiene, L. Hoch (until May 2011), N. Musee (until June 2011), H. Al-Jabri (until October 2010), S. Waller (until June 2011), C. Cosgrove (from July 2011), D.\u00a0Muninzwa (from October 2011), E.O.\u00a0Ohuma (from September 2010), D.\u00a0Yellappan (from November 2010), A.\u00a0Carter (from July 2011), D. Reade (from June 2012), R. Miller (from June 2012), ESU (from April 2016).Ultrasound Group: A.T. Papageorghiou (Head), L. Salomon , A. Leston, A. Mitidieri, F.\u00a0Al-Aamri, W. Paulsene, J. Sande, W.K.S. Al-Zadjali, C. Batiuk, S. Bornemeier, M.\u00a0Carvalho, M. Dighe, P. Gaglioti, N.\u00a0Jacinta, S. Jaiswal, J.A. Noble, K. Oas, M. Oberto, E. Olearo, M.G. Owende, J.\u00a0Shah, S. Sohoni, T. Todros, M.\u00a0Venkataraman, S.\u00a0Vinayak, L. Wang, D.\u00a0Wilson, Q.Q. Wu, S. Zaidi, Y. Zhang, P.\u00a0Chamberlain (until September 2012), D. Danelon (until July 2010), I. Sarris (until June 2010), J. Dhami (until July 2011), C. Ioannou (until February 2012), C.L. Knight (from October 2010), R.\u00a0Napolitano (from July\u00a02011), S.\u00a0Wanyonyi (from May 2012),\u00a0C.\u00a0Pace (from January 2011), V.\u00a0Mkrtychyan (from June 2012).Anthropometry Group: L. Cheikh Ismail (Head), W.C. Chumlea , F. Al-Habsi, Z.A. Bhutta, A. Carter, M. Alija, J.M. Jimenez-Bustos, J. Kizidio, F. Puglia, N.\u00a0Kunnawar, H. Liu, S. Lloyd, D. Mota, R. Ochieng, C. Rossi, M. Sanchez Luna, Y.J. Shen, H.E. Knight (until August 2011), D.A. Rocco (from June 2012), I.O. Frederick (from June 2012).Neonatal Group: Z.A. Bhutta (Head), E. Albernaz, M. Batra, B.A. Bhat, E\u00a0Bertino, P. Di Nicola, F. Giuliani, I.\u00a0Rovelli, K. McCormick, R. Ochieng, R.Y. Pang, V. Paul, V. Rajan, A.\u00a0Wilkinson, A. Varalda (from September 2012).Environmental Health Group: B.\u00a0Eskenazi (Head), L.A. Corra, H. Dolk, J. Golding, A. Matijasevich, T. de Wet, J.J. Zhang, A. Bradman, D. Finkton, O.\u00a0Burnham, F. Farhi.Brazil: F.C Barros , M. Domingues, S. Fonseca, A.\u00a0Leston, A. Mitidieri, D. Mota, I.K. Sclowitz, M.F. da Silveira.China: R.Y. Pang , Y.P. He, Y. Pan, Y.J. Shen, M.H. Wu, Q.Q. Wu, J.H. Wang, Y. Yuan, Y. Zhang.India: M. Purwar , A. Choudhary, S. Choudhary, S.\u00a0Deshmukh, D. Dongaonkar, M.\u00a0Ketkar, V. Khedikar, N. Kunnawar, C.\u00a0Mahorkar, I. Mulik, K. Saboo, C.\u00a0Shembekar, A. Singh, V. Taori, K.\u00a0Tayade, A. Somani.Italy: E. Bertino , P. Di Nicola, M. Frigerio, G. Gilli, P. Gilli, M. Giolito, F. Giuliani, M.\u00a0Oberto, L. Occhi, C. Rossi, I. Rovelli, F. Signorile, T. Todros.Kenya: W. Stones and M. Carvalho , J. Kizidio, R. Ochieng, J. Shah, S. Vinayak, N.\u00a0Musee (until June 2011), C.\u00a0Kisiang\u2019ani (until July 2011), D.\u00a0Muninzwa (from August 2011).Oman: Y.A. Jaffer , J. Al-Abri, J. Al-Abduwani, F.M.\u00a0Al-Habsi, H. Al-Lawatiya, B.\u00a0Al-Rashidiya, W.K.S. Al-Zadjali, F.R. Juangco, M. Venkataraman, H. Al-Jabri (until October 2010), D. Yellappan (from November 2010).UK: S. Kennedy , L. Cheikh Ismail, A.T. Papageorghiou, F. Roseman, A. Lambert, E.O. Ohuma, S. Lloyd, R. Napolitano (from July 2011), C. Ioannou (until February 2012), I. Sarris (until June 2010).USA: M.G. Gravett , C. Batiuk, M. Batra, S. Bornemeier, M. Dighe, K. Oas, W. Paulsene, D. Wilson, I.O. Frederick, H.F. Andersen, S.E. Abbott, A.A. Carter, H. Algren, D.A. Rocco, T.K. Sorensen, D. Enquobahrie, S. Waller (until June 2011)."} +{"text": "Nature Communications 10.1038/s41467-017-02730-7, published online 26 January 2018Correction to: The original version of this Article omitted the following from the Acknowledgements:\u201cThe technical support from SLAC Accelerator Directorate, Technology Innovation Directorate, LCLS laser division and Test Facility Division is gratefully acknowledged. We thank S.P. Weathersby, R.K. Jobe, D. McCormick, A. Mitra, S. Carron and J. Corbett for their invaluable help and technical assistance. Research at SLAC was supported through the SIMES Institute which like the LCLS and SSRL user facilities is funded by the Office of Basic Energy Sciences of the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The UED work was performed at SLAC MeV-UED, which is supported in part by the DOE BES SUF Division Accelerator & Detector R&D program, the LCLS Facility, and SLAC under contract Nos. DE-AC02-05-CH11231 and DE-AC02-76SF00515. Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515.\u201dand\u201cWork at BNL was supported by DOE BES Materials Science and Engineering Division under Contract No: DE-AC02-98CH10886. J.C. would like to acknowledge the support from National Science Foundation Grant No. 1207252. E.E.F. would like to acknowledge support from the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES) under Award No. DE-SC0003678.\u201dThis has been corrected in both the PDF and HTML versions of the Article."} +{"text": "AbstractDistephanus is native to Madagascar, the Mauritius, central and southern Africa, Yemen (Socotra Island), and China. The majority of the diversity is found in Madagascar. Here we provide new combinations for nine species of Vernonia that belong in Distephanus, all from Madagascar. All of the species were formerly placed in the large genus Vernonia, now greatly reduced.The genus Compositae that morphological and molecular data are being used (separately and together) to address generic limits. As a result we are seeing the breakup of many large non-monophyletic genera. In one such case, the genus Vernonia Schreb., of the tribe Vernonieae, has shrunk to about 20 species from North America and the remaining 1000 or so species from that genus are in the process of being assigned to other genera. Many of these \u201cnew\u201d genera were previously described and subsequently sunk into Vernonia, but others needed new names and descriptions. An overview of the tribe was presented by Vernonieae of Madagascar, tropical Africa, India, and SE Asia.As we continue to emerge from the \u201cDark Ages of Lumping\u201d it should come as no surprise to any student of the Vernonieae of Madagascar this effort concerns the establishment of proper limits for the genus Distephanus Cass. Described by Cassini based on a type removed from Conyza (Astereae), Distephanus has long been recognized as distinctive even when it was considered part of Vernonia . In addition to the type species three other species were described in Distephanus and therefore do not need to be transferred and a number of combinations have already been made: 24 by Distephanus. However, because of a lack of available herbarium material some of the Madagascar species names were left as Vernonia. After examining herbarium material from the Mus\u00e9um National d\u2019Histoire Naturelle (P), nine additional combinations can now be made. The following combinations are needed at this time because of upcoming entries in GenBank and determinations on specimens from a recent field trip in September-October of 2016. Descriptions and synonomy can be found in Distephanus now stands at 42 with possible new species to be described based on material collected during the aforementioned field trip.As part of a larger more comprehensive work on the Taxon classificationPlantaeAsteralesAsteraceae(Vatke) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161439-1Vernoniabakeri Vatke. Bremen Abh. Natuewiss. Vereins Bremen 9: 119. 1885.Taxon classificationPlantaeAsteralesAsteraceae(Humbert) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161440-1Vernoniacapuronii Humbert, Mem. Inst. Sci. Madagascar, S\u00e9r. B., B\u00edol. Veg. 6: 152. 1955.Taxon classificationPlantaeAsteralesAsteraceae(Drake) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161442-1Vernoniagrevei Drake. Bull. Soc. Bot. France 46: 240. 1900 Taxon classificationPlantaeAsteralesAsteraceae(Humbert) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161443-1Vernoniaibityensis Humbert, Notul. Syst. (Paris) 13(4): 313. 1949 Taxon classificationPlantaeAsteralesAsteraceae(Humbert) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161444-1Vernoniapoissonii Humbert, Notul. Syst. (Paris) 8(1): 6. 1939.Taxon classificationPlantaeAsteralesAsteraceae(Baker) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161445-1Vernoniapolytricholepis Baker, J. Linn. Soc., Bot. 21: 415. 1885Taxon classificationPlantaeAsteralesAsteraceae(Humbert) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161446-1Vernoniaquartziticola Humbert, Notul. Syst. (Paris) 13(4): 305. 1949 Taxon classificationPlantaeAsteralesAsteraceae(Baker) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161447-1Vernoniarhodopappa Baker. J. Linn. Soc., Bot. 22: 487. 1887Taxon classificationPlantaeAsteralesAsteraceae(Klatt) V.A.Funk & H.Robinsoncomb. nov.urn:lsid:ipni.org:names:77161448-1Vernoniaspiciformis Klatt. Ann. Nat. Hofmus. Wien 7: 296. 1892"} +{"text": "The following information is missing from the Funding section: J.R.P. and J.A.C. received travel funding under National Science Foundation Grant (PoLS) PHY-1026550."} +{"text": "Southeast (SE) Asia is 1 of the most biodiverse regions in the world, and it holdsapproximately 20% of all mammal species. Despite this, the majority of SE Asia's geneticdiversity is still poorly characterized. The growing interest in using environmental DNAto assess and monitor SE Asian species, in particular threatened mammals\u2014has created theurgent need to expand the available reference database of mitochondrial barcode andcomplete mitogenome sequences. We have partially addressed this need by generating 72 newmitogenome sequences reconstructed from DNA isolated from a range of historical and moderntissue samples. Approximately 55 gigabases of raw sequence were generated. From this data,we assembled 72 complete mitogenome sequences, with an average depth of coverage of \u00d7102.9and \u00d755.2 for modern samples and historical samples, respectively. This dataset represents52 species, of which 30 species had no previous mitogenome data available. The mitogenomeswere geotagged to their sampling location, where known, to display a detailed geographicaldistribution of the species. Our new database of 52 taxa will strongly enhance the utilityof environmental DNA approaches for monitoring mammals in SE Asia as it greatly increasesthe likelihoods that identification of metabarcoding sequencing reads can be assigned toreference sequences. This magnifies the confidence in species detections and thus allowsmore robust surveys and monitoring programmes of SE Asia's threatened mammal biodiversity.The extensive collections of historical samples from SE Asia in western and SE Asianmuseums should serve as additional valuable material to further enrich this referencedatabase. Southeast (SE) Asia is 1 of the most biodiverse regions in the world, hosting \u223c20% ofmammal species, but it is experiencing rapid deforestation for agriculture anddevelopment. To assess the ecological consequences of land use change, there is growinginterest in using environmental DNA to monitor mammal populations, particularly threatenedtaxa that often underpin conservation policies . Yet curGenomic DNA was extracted from different sample types of 72 small mammals, comprising 52species, listed in Table\u00a0Mitogenomes were generated using several approaches. In Copenhagen, author F.M.S.constructed Illumina shotgun libraries with insert sizes ranging between 50 and 400 bp. Toconstruct libraries, DNA was sheared to the target size range using Bioruptor\u00ae XL and converted into an Illumina-compatiblesequencing library using the NEBNext E6070 Kit . The librarieswere polymerase chain reaction (PCR) amplified with index primers and purified usingQiaquick columns according to the manufacturer's instruction. Multiplde novo and reference-based assemblyusing SOAPdenovoTrans v. 1.03 [Raw reads for F.M.S. samples were assembled independently by authors F.M.S. and F.P.using 2 different approaches, then compared for consistency. Author F.M.S. trimmed thereads for sequencing adapters, low-quality stretches, and leading/tailing Ns usingAdapterRemoval 1.2 . The mit_013268) and MITO_013268) and Basi_013268) asreferFor the mitogenome constructed by author R.M., Illumina sequence reads werede-multiplexed according to the respective indexes with the Illumina software bcl2fastq v.2.17 , and adapters were clipped from the sequence readswith the software cutadapt v. 1.3 . QualityNumbers of raw reads generated for each sample and mapping statistics for all 72mitogenome assemblies are shown in All the sequenced mitogenomes were aligned using MAFFT v. 7.158b using thWe anticipate that the now-expanded mitogenome reference dataset for SE Asian mammals willprovide benefits for a number of research areas. First, it should enhance the power ofenvironmental DNA and other metabarcoding/barcoding approaches that relate to theidentification of SE Asian mammals by conferring the ability to identify more species to thespecies level. This in turn has practical applications for those monitoring SE Asia'sthreatened mammal biodiversity, combatting trade in mammal species and so on. Second, thedata will also have relevance to phylogenetic and population studies based on mtDNA data,which will be of use as we investigate the evolutionary history of this biodiversityhotspot.GigaScience repository, GigaDB [Raw shotgun data are deposited in the SRA under bioproject number PRJNA361218 and areavailable in the , GigaDB . Details, GigaDB .1. Additional file 1: DNA extraction of historical samples, library construction, andprimer information2. Additional file 2: Sample information sheet of mitogenomes assembled in this work3. Additional file 3: Alignment of mitogenomes assembled in this work4. Additional file 4: Newick file for phylogenetic treeBLAST: Basic Local Alignment Search Tool; bp: base pair; GATK: Genome Analysis Toolkit;MAFFT: Multiple Alignment using Fast Fourier Transform; NCBI RefSeq: National Center forBiotechnology Information Reference Sequence Database; PCR: polymerase chain reaction;RAxML: Randomized Axelerated Maximum Likelihood; SE: southeast.The authors declare that they have no competing interests.This project was funded by the Malaysian Government (F.M.S.), Lundbeck Foundation grantR52\u20135062 (M.T.P.G.), Leibniz-Association grant SAW-2013-IZW-2 (J.F.), the German FederalMinistry of Education and Research grant BMBF FKZ: 01LN1301A (A.W.), and the German PrimateCenter (C.R.).F.M.S., A.W., J.F., and M.T.P.G. conceived the project. F.M.S., M.H.S.S., M.S.S., M.S.A.,R.M., P.R.P., C.R., B.K.L., and S.J.R. collected the samples and extracted the genomic DNA.F.M.S., R.M., P.R.P., and C.R. constructed the libraries and did sequencing. F.M.S., J.R.M.,F.P., S.L., P.R.P., R.M., D.L., and C.R. assembled the mitogenomes and performed mitogenomeanalysis. F.M.S., S.L., P.R.P., and M.T.P.G. wrote the article. All authors discussed theproject and data. All authors read and approved the final manuscript.GIGA-D-17-00015_Original-Submission.pdfClick here for additional data file.GIGA-D-17-00015_Revision-1.pdfClick here for additional data file.GIGA-D-17-00015_Revision-2.pdfClick here for additional data file.Response-to-Reviewer-Comments_Original-Submission.pdfClick here for additional data file.Response-to-Reviewer-Comments_Revision-1.pdfClick here for additional data file.Reviewer-1-Report-.pdfClick here for additional data file.Reviewer-1-Report-(Revision-1).pdfClick here for additional data file.Reviewer-2-Report-.pdfClick here for additional data file.Additional-filesClick here for additional data file."} +{"text": "AbstractGalactia in the eastern USA necessitate additional typifications to stabilize the taxonomy. Galactiapurshii is lectotypified here as the earliest available but overlooked name for a fairly common species of the Atlantic Coast and peninsular Florida. Galactiavolubilis is epitypified here since the characterization of the species has been limited by its lectotype being an illustration. A lectotype is designated for Galactiapilosavar.angustifolia, a form with narrow leaves here considered synonymous with G.volubilis.The pervasive difficulties encountered with studying Galactia P.Galactia is most diverse in Texas and Florida have had a turbulent taxonomic history, with the application of many names being excessively multifarious. Studies of type specimens and taxonomic history in Galactia require meticulous scrutiny. Typifications are still needed to further stabilize taxonomy in Galactia. A lectotype is designated for G.purshii Desv. and its application is discussed. An epitype is designated for G.volubilis (L.) Britton and a lectotype is designated for one of its synonyms, G.pilosaNutt.var.angustifolia Torr. & A.Gray.The 10\u201315 species of Taxon classificationPlantaeFabalesFabaceaeDesv., Ann. Sci. Nat. (Paris) 9: 413. 1826GalactiapurshiiGalactiaglabella DC., Prodr. 2: 238, 1825 nom. illeg. (Art. 53.1) non G.glabella Michx. Fl. Bor.-Amer. (Michaux) 2: 62. 1803 nom. illeg. (Art. 52). Lectotype (designated here): Carol. [Carolina] mer. [meridionale], Fraser s.n. (G [G00726366]). =GalactiafloridanaTorr. & A.Grayvar.longeracemosa Vail, Bull. Torrey Bot. Club 22: 505. 1895. Lectotype . syn. nov. =Galactiamichauxii A.R.Franck, Phytologia 99: 148\u2013149. 2017. Type: USA, Florida, Palm Beach Co., W side of US 1, Juno Beach area, 21 Apr 1962, Lakela 24958 . syn. nov. Desv., Ann. Sci. Nat. (Paris) 9: 413. 1826. Galactia found along the Atlantic Coast and Florida peninsula, USA, that still lacks stable nomenclature is characterized by its strigose stems that are prostrate to occasionally twining or climbing, petioles usually shorter than the terminal leaflet, leaflets often drying to a darkened or brownish color with conspicuous reticulate venation adaxially and prominent secondary venation abaxially, flower buds usually acuminate at the apex, and non-villous flowers 10\u201318 mm long not drying reddish that are often congested together near the apex of the inflorescence. The earliest applicable name for this species is G.purshii, a name chiefly ignored, and the recently introduced G.michauxii A.R.Franck is a synonym. This species had previously gone under several misapplied names, including G.glabella Michx., nom. illeg. (G.regularis (L.) Britton et al. . The Michaux specimen is similar to other specimens of G.purshii that have some moderately twining stems such as Daoud 49 (USF) from North Carolina, Kral 11078 (USF) from Virginia, and Seymour 91 7 20 (USF) from Virginia, each of which had been previously annotated with three different names: G.glabella, G.regularis, and G.volubilis. The Michaux specimen had also been identified as G.volubilis partly because of the twining found on the specimen so far remains untypified. Within Galactia its precise application may be relatively inconsequential since its specific epithet is blocked by G.volubilis (L.) Britton. Additionally, the species of Galactia in the eastern USA are likely to remain in Galactia as they appear to be closely related to the type species of Galactia, G.pendula Pers., and part of a monophyletic clade based on a recent DNA phylogeny with the abbreviation \u201cexcl. syn.\u201d By excluding E.volubile, Desvaux excluded G.glabella since it is a superfluous name homotypic with E.volubile. Furthermore, for his second species, G.glabella of Michaux, and included G.pilosa as its synonym. Galactiapilosa is currently considered a synonym of G.mollis and the ambiguously described E.volubile (=G.glabella) might also be conspecific with G.mollis , any specimens seen by Candolle for his treatment should be considered original material . G.brachypoda (NY), described it as erect, 1\u20131.5 feet high and with a woolly calyx, noting his descriptions were \u201call my own, copying no one, when I knew the plant\u201d Vail]\u201d which was later crossed out by a different pen, possibly by Torrey who also added what appears to be \u201cbrevipedunculata n. sp.\u201d to the same label. G.brachypoda, none of which match the concept of G.purshii.The name sapplied , 2017 toPageBreakPageBreakG.brachypoda has sometimes been described as similar to G.purshii. However, the descriptions of a decumbent with stems well over 40 cm long described on its label \u201crobust, erect plants with limited twining\u201d and was noted to be very similar to the type specimens of G.brachypoda . It does not appear to be impossible for G.brachypoda to be erect and have stems to 37 cm long. The characterization of G.brachypoda as erect by Anderson 15642 is considered here to be accurate.The habit of ecumbent , ascendiecumbent , procumbecumbent , or prosecumbent for G.b cm long , anotherachypoda . FurtherG.brachypoda with G.erecta . G.brachypoda as \u201cvery sparse,\u201d dissimilar to other observations of the calyx as villous (Duncan 17113 [GA]) seems to mix features of G.erecta and G.mollis in that it has subsessile inflorescences and long petioles like G.erecta and long, partly twining stems like G.mollis. Lastly, the left-most plant of a Chapman collection at MO (793008) appears erect like G.erecta but has shortly pedunculate inflorescences and indumentum more like G.mollis.Numerous authors noted a semblance of .erecta , while oimmature , the siz villous , woolly villous , or \u201cclo villous . AnotherG.brachypoda at NY (00008088 and 00008090), although there is a third specimen (NY [00008089]) that was labeled as G.brachypoda in Chapman\u2019s handwriting. This third specimen is clearly G.erecta. It had been proposed that other authors were attempting to make two species out of G.erecta with the use of the name G.brachypoda through the study of this G.erecta specimen labeled as G.brachypoda .\u201d The evidence does not support the idea that this specimen (NY [00008089]) nor any other of G.erecta was used to formulate concepts of G.brachypoda. I concur with previous botanists that G.brachypoda is closely related to G.erecta and G.mollis, and numerous features associated with the type specimens of G.brachypoda are inconsistent with G.purshii.There are two known type specimens of achypoda , 2017. TTaxon classificationPlantaeFabalesFabaceae(L.) Britton, Mem. Torrey Bot. Club 5: 208. 1894GalactiavolubilisHedysarumvolubile L., Sp. Pl. 2: 750. 1753. Lectotype : Dillenius, Hort. Eltham. t. 143., f. 170. 1732. Epitype (designated here): USA, Florida, Lafayette Co., NFMYC , 13 Jun 1964, Caudle et al. 5744 . =Galactiamacreei M.A.Curtis, Boston J. Nat. Hist. 1: 120. 1835. GalactiapilosaNutt.var.macreei (M.A.Curtis) Torr. & A.Gray, Fl. N. Amer. 1: 287. 1838. Type: USA, North Carolina, Curtis s.n. Brittonvar.intermedia Vail, Bull. Torrey Bot. Club 22: 508. 1895 nom. illeg. (Art. 52). Lectotype (designated here): USA, Florida, Lt. Alden s.n. . (L.) Britton, Mem. Torrey Bot. Club 5: 208. 1894. Galactia as demonstrated by G.regularis. Since G.volubilis is lectotypified by an illustration, an epitype would be useful to help secure the application of G.volubilis and further allay any possible confusion with other taxa. No information is known for the provenance of the PageBreakG.volubilis plant in Sherard\u2019s garden, which was used for the Dillenius lectotype illustration. An epitype was sought here that closely matches the morphology supplied by Dillenius.Precise measurements of flower size and plant indumentum can be essential towards the application of names in Caudle et al. 5744 (USF) Fig. is choseCaudle et al. 5292A and 5292B, are very likely isoepitypes. In all features, they are markedly identical in morphology to the epitype, including the development of inflorescences with only immature fruits. The collection numbers of the labels are different but they do not appear to be traditional collection numbers. The specimens were gathered by several undergraduate students as part of a few National Science Foundation (NSF) grants awarded to Margaret L. Gilbert, the curator of the Florida Southern College herbarium . It appears this sequence of collection numbers was given to any specimen under the purview of these NSF grants, and were simply sequentially added as the specimens were processed back at the herbarium. It seems likely that these G.volubilis specimens were gathered by one group of students but later processed separately resulting in their sequential separation. Although several students and the curator were all involved with the field work, Carol F. Caudle (now Carol Baskin) related that she herself was the main person responsible for the herbarium specimens , which likely came from near Croom\u2019s properties in the Florida panhandle in 1832 and Fort King from 1832\u20131833 , Hansen 5972 (USF), Hansen 9896 (USF), and Popenoe 2080 (USF). The linear-oblong leaflets (> 4 times as long as wide) of G.austrofloridensis only subtly distinguish it from G.volubilis. One collection from the West Indies, Correll & Correll 47675 from the Bahamas, appears identifiable as G.austrofloridensis. Galactiagrisebachii Urb., possibly endemic to Cuba (e.g. Le\u00f3n 7461 [NY]), has similarly linear-oblong leaflets (Galactiaparvifolia A.Rich, of the Greater Antilles and Bahamas, is similar to G.grisebachii but may differ by its lateral leaflets often being ca. \u00bd as long as the terminal leaflet (The leaflet shape of leaflets but seemleaflets . The poo leaflet ."} +{"text": "Haemaphysalis erinacei is one of the few ixodid tick species for which valid names of subspecies exist. Despite their disputed taxonomic status in the literature, these subspecies have not yet been compared with molecular methods. The aim of the present study was to investigate the phylogenetic relationships of H. erinacei subspecies, in the context of the first finding of this tick species in Romania.H. e. taurica (from Romania and Turkey), four adults of H. e. erinacei and 17 adults of H. e. turanica (from China). From these samples fragments of the cytochrome c oxidase subunit 1 (cox1) and 16S rRNA genes were amplified via PCR and sequenced. Results showed that cox1 and 16S rRNA gene sequence divergences between H. e. taurica from Romania and H. e. erinacei from Italy were below 2%. However, the sequence divergences between H. e. taurica from Romania and H. e. turanica from China were high (up to 7.3% difference for the 16S rRNA gene), exceeding the reported level of sequence divergence between closely related tick species. At the same time, two adults of H. e. taurica from Turkey had higher 16S rRNA gene similarity to H. e. turanica from China (up to 97.5%) than to H. e. taurica from Romania (96.3%), but phylogenetically clustered more closely to H. e. taurica than to H. e. turanica.After morphological identification, DNA was extracted from five adults of H. erinacei in Romania, and the first phylogenetic comparison of H. erinacei subspecies. Phylogenetic analyses did not support that the three H. erinacei subspecies evaluated here are of equal taxonomic rank, because the genetic divergence between H. e. turanica from China and H. e. taurica from Romania exceeded the usual level of sequence divergence between closely related tick species, suggesting that they might represent different species. Therefore, the taxonomic status of the subspecies of H. erinacei needs to be revised based on a larger number of specimens collected throughout its geographical range.This is the first finding of Haemaphysalis Koch, 1844 is the second largest genus (following Ixodes) of hard ticks (Acari: Ixodidae), including 167 species [Haemaphysalis erinacei Pavesi, 1884 occurs in Mediterranean forests, woodlands and scrub [H. erinacei are terrestrial mammals, such as hedgehogs and carnivores for adult ticks [Rickettsia massiliae [R. raoultii [R. heilongjiangensis [lt ticks . Bats, braoultii and R. hangensis ).Fig. 1DHaemaphysalis erinacei is one of the few ixodid tick species for which valid names of subspecies exist. Subspecies are conspecific taxa, representatives of which show differences in morphology and geographical range from each other, but can naturally interbreed. Accordingly, until now H. erinacei subspecies were described on the basis of different morphology and geographical range, but this resulted in a controversy in their taxonomy. Camicas et al. [H. erinacei, namely H. e. erinacei Pavesi, 1884 (described from Tunisia), H. e. ornata Feldman-Muhsam, 1956 (described from Israel), H. e. taurica Pospelova-Shtrom, 1940 (described from Crimea) and H. e. turanica Pospelova-Shtrom, 1940 (described from Tajikistan). According to Hoogstraal [H. erinacei includes three subspecies: H. e. erinacei in North Africa, H. e. taurica in the Middle East (including western states of the former Soviet Union) and H. e. turanica in Central Asia. Haemaphysalis e. erinacei also occurs in southern Europe, in particular in Spain, Italy and the western Balkans [H. e. taurica is present in the eastern Balkans [H. e. taurica and H. e. turanica are widely distributed in certain regions of Central Asia were investigated, in the context of the first finding of this tick species in Romania.Despite this taxonomic controversy, no studies have attempted molecular phylogenetic comparison of c oxidase subunit 1 (cox1) and 16S rDNA genes are well-established barcoding genes for molecular identification and phylogenetic analyses of ticks [H. e. taurica, H. e. erinacei and H. e. turanica in the present study.Cytochrome of ticks \u201316. TherH. erinacei were included in this study (Table\u00a0H. e. erinacei) and Filippova [H. e. turanica, H. e. taurica). Pictures were produced with a VHX-5000 digital microscope.Altogether 26 adults of dy Table\u00a0. The subilippova (H. e. tc oxidase subunit 1 (cox1) gene using the primers HCO2198 (5\u2032-TAA ACT TCA GGG TGA CCA AAA AAT CA-3') and LCO1490 (5\u2032-GGT CAA CAA ATC ATA AAG ATA TTG G-3\u2032) [cox1 gene , and PCR conditions were different .DNA was extracted with QIAamp DNA Mini Kit as described , includiTG G-3\u2032) . ReactioTG G-3\u2032) . Concernhttps://blast.ncbi.nlm.nih.gov). Representative sequences were submitted to the GenBank database , and are referenced according to accession numbers.PCR products were visualized in 1.5% agarose gel. Purification and Sanger dideoxy sequencing for samples from Romania, Italy and Turkey was done by Biomi Inc. , and for samples from China by Sangon Biotech Co. . The newly-generated sequences were manually edited, aligned and compared to reference GenBank sequences by nucleotide BLASTN program , and 99.4% identical with H. e. erinacei from Italy, but had only 94.6\u201395.1% similarity with isolates of H. e. turanica from China (Table\u00a0H. e. taurica from Romania showed 99.3% similarity with one specimen of H. e. taurica collected in Turkey (Tokat province), and 98\u201398.3% similarity with H. e. erinacei from Italy. On the other hand, the 16S rRNA fragment of H. e. taurica from Romania had only 92.7\u201395.3% similarity with isolates of H. e. turanica from China.The cox1 and 16S rDNA gene sequence divergences between H. e. taurica from Romania and Turkey (Tokat province) and H. e. erinacei from Italy were low (below 2%). This may be consistent with allopatric separation of these two subspecies and I. ricinus (GU074592) is 98.2% (383/390\u00a0bp), amounting to 1.8% difference [H. e. taurica and H. e. turanica.Taken together, the istances . Howeverfference , the seqH. e. taurica than to H. e. taurica from Romania (96.3%) , which were morphologically identified as adults of ica Fig.\u00a0 had high%) Table\u00a0. HoweverH. e. taurica, H. e. erinacei and H. e. turanica are well reflected by the topology of cox1 phylogenetic tree, with H. e. taurica and H. e. erinacei clustering close to each other, but separately from H. e. turanica , Turkey (KR870978) and China (KF547980) with 100% 16S rRNA gene identity.Several factors may have contributed to this divergence and its maintenance. Southern peninsulas of Europe acted as major refugia during ice age(s), from which genetically distinct clades of animal species emerged , as alsopian Sea may haveerinacei , whereasconcinna ; or H. pH. e. taurica and H. e. turanica are common, these two tick subspecies exhibit biotope isolation in overlapping parts of their geographical range [In addition, based on an extensive collection material, while the hosts of al range , which mH. erinacei in Romania, and the first phylogenetic comparison of H. erinacei subspecies. Phylogenetic analyses do not support that the three H. erinacei subspecies evaluated here are of equal taxonomic rank. In particular, the genetic divergence between H. e. turanica from China and H. e. taurica from Romania exceeded the usual level of sequence divergence between closely related tick species, suggesting that they might represent different species. Therefore, the taxonomic status of the subspecies of H. erinacei needs to be revised based on a larger number of specimens collected throughout its geographical range.This is the first finding of"} +{"text": "Scientific Reports7: Article number: 42429; 10.1038/srep42429 published online: 02142017; updated: 07272017.M. Payvand, A. Madhavan, A. Ghofrani and L. Theogarajan were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as in the Supplementary Information that now accompanies the Article.The Author Contributions section now reads:B. C. wrote the manuscript and fabricated the hybrid CMOS/3D memristor chip. M. A. L.-M. and A. G. designed the architecture and the digital circuitry of the CMOS chip. M. P. (Payvand) designed the analog circuitry and M. P. (Payvand) and A. M. designed the overall layout of the CMOS chip. M. A. L.-M. created the user-interface for electrical measurements. Both B. C. and M. A. L.-M. conducted the electrical characterizations and analyzed the data. G. A. contributed in the chemical mechanical planarization of the CMOS chip as well as the tuning operation of the memristors. M. P. (Prezioso) contributed to develop strategies for electrical characterization of the memristor crossbars. B. H. was involved in the non-stoichiometric TiO2-x thin film depositions. L. T., K. T. C. and D. B. S. have supervised the overall project. All authors have seen and approved of the manuscript before submission."} +{"text": "The correct reference is: Gardner, L., Fajardo, D., Waller, S. T., Wang, O., and Sarkar, S. 2012. \u201cA Predictive Spatial Model to Quantify the Risk of Air-Travel-Associated Dengue Importation into the United States and Europe.\u201d Journal of Tropical Medicine 2012: Article ID 103679. DOI: The following information is missing from the Acknowledgments section: Figure 1 was generated by O. Wang using a template due to SS and V. Sanchez-Cordero. Thanks are due to them and to the following individuals for participating in the dengue project at the University of Texas: D. Fajardo, P. Illoldi-Rangel, M. Linaje, M. Pool, and S. Strutz."} +{"text": "AbstractDepressariaalbarracinella Corley, sp. n., Agonopterixcarduncelli Corley, sp. n. and Agonopterixpseudoferulae Buchner & Junnilainen, sp. n. and the subspecies DepressariasaharaeGast\u00f3n & Vivesssp.tabelli Buchner, ssp. n. are described.The species Depressariaalbarracinella was first found in Spain in 1969 and recognised as apparently new but the specimens in NHMUK have remained undescribed. Additional Spanish material has been located in ZMUC and other collections and three specimens have been found from Greece.Agonopterixcarduncelli. A single male of an unidentified Agonopterix of the pallorella group was found in Algarve, Portugal in 2010. A search for larvae in March 2011 was successful and one male and one female were reared from Carthamuscaeruleus. Additional specimens of the new species have been located in collections from Spain, Greece and Morocco.Agonopterixpseudoferulae. A specimen from Greece with the name Agonopterixferulae found in the Klimesch collection in ZSM had forewing markings which suggested that it might be a different species. Further specimens from Italy and Greece have been examined, among them two reared from Elaeoselinumasclepium (Apiaceae). Both genitalia and barcode show that this is an undescribed species.Depressariasaharae Gast\u00f3n & Vives, 2017 was described very recently (D.saharaessp.tabelli Buchner, ssp. n.recently from norPageBreak Depressariinae in the series Microlepidoptera of Europe has revealed a number of taxonomically challenging species groups in the genera Agonopterix H\u00fcbner [1825] and Depressaria Haworth, 1811. This was not unexpected but there are more such groups than we had initially expected. However, in addition to the problem groups, some undescribed species have also been discovered which can be described without the necessity to resolve complex taxonomic issues. Two such species are described here in Agonopterix and one species and one subspecies in Depressaria.Preparatory work for a proposed volume on Material has been examined from NHMUK, NHMV, TLMF, ZMUC, ZSM and additionally specimens from many private collectors including those of the authors have been checked, here only listed if the material was of particular importance for this paper: Michael Dale (England), Gabriele Fiumi , Knud Larsen (Denmark), Toni Mayr (Austria), Willibald Schmitz (Germany), Peter Sonderegger (Switzerland), Lubom\u00edr Srnka (Slovakia), Jan \u0160umpich (Czech Republic) and Joachim Viehmann (Germany). Apart from one exception given in the description, each species includes both reared and light-trapped specimens.Morphological examination and photographic documentation. Genitalia preparations followed standard techniques (Robinson 1976). Male preparations were stained with mercurochrome and females with chlorazol. The placement of holotypes is given under each species. Photographic documentation: Apart from two exceptions given in the descriptions, photos of specimens in total view were taken with Canon EOS 5D Mark III and Canon lens EF 100mm 2.8 L IS USM at 1:1., specimens were illuminated with two diffused flashes, using a third flash for setting the background whiteness. Detailed photos of specimens were taken with a Canon lens MP-E 65 at 2:1, using ring flash. Genitalia photos were taken with microscope (Wild Heerbrugg) using a 10x objective and a 2.5x ocular. Photos were edited using the software Helicon Focus 4.80 and Adobe Photoshop 6.0. For creating the black and white photos, based on the used stain, the G alpha channel of the RGB originals was used in males and the Y alpha channel of the CMYK originals in females. Genitalia examination and photos by P. Buchner, if not specified.DNA-Barcoding. The full length lepidopteran DNA barcode sequence is a 658 basepair long segment of the 5\u2019 terminus of the mitochondrial COI gene (cytochrome c oxidase 1). DNA samples (dried leg) were prepared according to the accepted standards PageBreakand were processed at the Canadian Centre for DNA Barcoding to obtain DNA barcodes using the standard high-throughput protocol described in http://www.boldsystems.org/index.php/Public_SearchTerms?query=DS-DEEUR330, dx.doi.org/10.5883/DS-DEEUR330) in the Barcode of Life Data Systems Natural History Museum , London, United KingdomNHMV Naturhistorisches Museum, Vienna, AustriaNMPC National Museum, Prague, Czech RepublicTLMF Tiroler Landesmuseum Ferdinandeum, Innsbruck, AustriaZMUC Zoological Museum, University of Copenhagen, DenmarkZMUH Zoology Museum, University of Helsinki, FinlandZSM Zoologische Staatssammlung M\u00fcnchen, GermanyTaxon classificationAnimaliaLepidopteraDepressariidaeCorleysp. n.http://zoobank.org/69805CE8-47FC-43FA-BE58-06F6DB16C946Spain, Granada, Sierra Nevada, Collado del Lobo, north side, 2300 m.Depressariaalbarracinella Corley, teste M. Corley, 2004 | B.M. \u2642 Genitalia slide No. 30716 | Corley prep. 1915m.\u2642 Sierra Nevada, Collado del Lobo, North Side, 2300 m, 14.vii.1969 | Hispania mer. K. Sattler & D.J. Carter. BM 1970-26 | HOLOTYPE Spain: \u2640 Sierra Nevada, Collado del Lobo, North Side, 2300 m, 14.vii.1969, Hisp. mer. K. Sattler & D.J. Carter. BM 1970-26, Depressariaalbarracinella Corley, det. M. Corley, 2004; \u2642 Prov. Granada, Sierra Nevada, Puerto de la RaPageBreakgua, 1000m, 1.vii.1969 K. Sattler & D.J. Carter. NHMUK prep. 18856 (NHMUK); \u2640 Andalusia, Sierra Nevada, Camina de Veleta, 2300 m, 23.x.1983, leg. E. Traugott-Olsen (ZMUC); 6 \u2642\u2642, 2 \u2640\u2640, Spain, Almer\u00eda, Sierra de los Filabres, Alto del Calar del Gallinero, 1900\u20132022m, 17.-18.vi.2007, J. \u0160umpich leg. et det. (NMPC); 2 \u2640\u2640, Spain, Almer\u00eda, Sierra de los Filabres, route Purchena \u2013 Sen\u00e9s, 1600m, 16.vi.2007, J. \u0160umpich leg. et det. (NMPC); \u2642 Castell\u00f3n, Banderetta Pass, 800 m, 17.vii.1992, leg. M. Fibiger (ZMUC); \u2642 Teruel, Albarracin, Val de Vecar, 1250 m, 17\u201318.vii.1981, leg. M. Fibiger (ZMUC) (Corley gen. prep. 1711); \u2640 Teruel, Albarracin, Val de Vecar, 15.vii.1992. M. Fibiger (ZMUC) (Corley gen. prep. 1717); \u2642 Teruel, Albarracin, 1150 m, 3.v.2002, leg. K. \u010cern\u00fd, det. P. Buchner; \u2640 Zaragosa, Bujareloz, 6 km, \u2640, 300m 29.v.2015, leg. J. Viehmann, det P. Buchner; \u2642 Huesca, Candasnos, 10 km S, 30.v.2015, leg. J. Viehmann, det P. Buchner.Greece: \u2642 Central Greece, Parnassos Mountains, 1 km NE Arachova, 1070 m, 9.vi.2013, leg. P. Skou (ZMUC), det. P. Buchner; 2\u2642\u2642 Lesbos, Molivos, 6.vi.1994 (gen.prep. DEEUR 5398) and 7.vi.1994, leg. J.P. Baungaard (ZMUC), det. P. BuchnerD.albarracinella differs from other species of the veneficella group in the very weak or obsolete dark forewing markings and the absence of a dark spot at base of dorsum, but it is more reliably separated from other species in the group by various characters involving different proportions of one part of the male genitalia relative to another. This is best set out in a key.Externally D.pentheri Rebel, 1904 is omitted due to insufficient knowledge of this taxon. The North African D.deverrella Chr\u00e9tien, 1915, has sometimes been listed as present in France, but we can find no evidence for this.The key below includes only the European species. Depressariaveneficella group ; TLMF Lep 19150 ; TLMF Lep 17687 .Neighbour-joining analysis , currently with 13 species described from the Palaearctic region extending from western Europe and North Africa through the Middle East to central Asia, with the most eastern records from north-east China, Mongolia and the Altai region of Siberia. D.erzurumella Lvovsky, 1996 from Turkey, provided a key based on male genitalia to 11 species, omitting D.pentheri Rebel, 1904, which was known only from the female. Subsequently he described D.kailai Lvovsky, 2009 , valvae incurved at apex, costal margin sometimes with median bulge, sacculus widely crossing the valva with two (rarely three) processes on the posterior edge, the outer reaching close to the costal margin of valva or exceeding it, saccus often elongate, aedeagus slender, long with a single cornutus. Female genitalia with long ductus bursae. Species identification most often rests on the male genitalia, where the shape of the incurved apex of the valva, the length of the saccus and the relative proportions of the various parts provide diagnostic characters, in particular the length of the cornutus relative to the aedeagus and the length of the aedeagus relative to the length of the valva. Those species with known food-plants all feed on Apiaceae.The NHMUK since that date. Further specimens were later collected in the same area and elsewhere in Spain, most of these deposited in ZMUC. It was these that first came to the notice of M. Corley in 2004. Recently the species has been found in additional localities in Spain and in Greece. It is described here as D.albarracinella Corley sp. n.The presence of an undescribed species of this group in Spain was recognised by Klaus Sattler after he and David Carter collected several specimens in Sierra Nevada in 1969. These have remained unnamed in The specimens from Greece have not been included in the type series. Although there is no reason to doubt the identification, the p-distance of over 1% between the barcodes of Spanish and Greek specimens suggests that caution is not out of place.Taxon classificationAnimaliaLepidopteraDepressariidaePageBreakCorley, sp. n. http://zoobank.org/F0BDBC85-90F3-41B9-8CE1-8DECC95F9CF837\u00b08'N; 8\u00b01'W.Portugal, Algarve, Boliqueime, 70 m, Portugal, Algarve, Boliqueime, 24.xi.2011, M.J. Dale | Agonopterixcarduncelli Corley Holotype | slide MD01355, DEEUR photo 0758 A.carduncelli | DNA barcode id. TLMF Lep 07015. Specimen to be deposited in NHMUK.\u2642, Portugal: 1 \u2642, Algarve, Boliqueime, 20.xi.2010, M.J. Dale, gen.prep. DEEUR 0757, in coll M.J. Dale; 1 \u2642, Algarve, Mexilhoeira Grande, Cruzinha, 15.v.2011 ex l. iii.2011, Carthamus (Carduncellus) caeruleus, leg. M.F.V. Corley, DEEUR 0777, in coll. M. Corley; 1 \u2640, same data but emerged 23.v.2011, gen. prep. DEEUR 0776, in coll. M. Corley; Spain: 1 \u2642, Cuenca, Izotely, 30.ix.2008, leg. L. Srnka, gen. prep. DEEUR 2183, det. P. Buchner; Greece: 1 \u2640, Messalongi Galatas, 5.v.2007, W. Schmitz, DEEUR 4404, det. P. Buchner; Morocco: 1 \u2642, 1 \u2640, High Atlas, Ifrane, 30.vi.1972, leg. F. Hahn, gen. prep. DEEUR 1983 (\u2642) bzw DEEUR 1980 (\u2640), det. P. Buchner; 1 \u2642 same locality, 2.vii.1972, G. Friedel (ZSM), gen. prep. DEEUR 1677, det. P. Buchner.A.straminella is most similar with black dot at base of dorsum and black terminal dots together with paler hindwing, but lacks cell dots. Forms of A.carduncelli sp. n. without evident cell dots require genitalia examination to distinguish them from A.straminella. Other related species have better developed cell dots. In the male genitalia, A.carduncelli sp. n. is recognisable by the longer curved cuiller and broader valva in comparison with related species. The female is unique among European Agonopterix in the absence of a signum.The characteristic shape of segment 2 of the labial palp and the absence of a posterior crest on the thorax are features shared with a few other species mostly with similar coloration. Description. Adult caeruleus, e.p. 23.v.2011, leg., cult. and coll. M. Corley P9827); TLMF Lep 06994 caeruleus, e.p. 15.v.2011, leg., cult. and coll. M. Corley P9824, gen. prep. DEEUR 0776); TLMF Lep 07015 ; TLMF Lep 07017 .Neighbour-joining analysis shows Agonopterixmultiplicella as the nearest neighbour with 1.83% p-distance and A.straminella (BOLD:ABZ7581) as the second nearest neighbour with 2% p-distance. Intraspecific variability, based on present knowledge, 0.16% within the Portugese population. So far, genetic data are available only from Portugese specimens.A.carduncelli sp. n. and A.multiplicella. The latter species has none of the characters of the pallorella group.Differences in DNA barcodes arise over time through chance mutations. Such stochastic events sometimes lead to fairly unrelated species appearing as nearest neighbours. This is evidently the case with Carthamus [=Carduncellus] caeruleus (Asteraceae).The species name, a noun in genitive case, is derived from the larval food-plant Currently known only from Portugal, Spain, Greece and Morocco, but potentially more widespread around the Mediterranean with its food-plant.PageBreakCarthamuscaeruleus (L.) C. Presl in late March before the flowers develop. Larvae from Algarve collected on 17 March 2011 emerged in captivity in May. Small larvae were collected on 25 March 2017 and reared on by J. Nunes. Two reached the final instar , A.kaekeritziana , A.bipunctosa , A.broennoeensis Strand, 1920, A.straminella and A.squamosa . A few other described taxa are synonyms of the above mentioned species. However one species has been previously overlooked and is described here as A.carduncelli sp. n. species mainly iAgonopterix feeding on Carthamnus in Algarve, Portugal was suspected from the late 1990s when empty spinnings were found by M. Corley on the plant in late April. After Michael Dale found an adult of an undescribed species in 2010, a visit to Algarve in March 2011 by M. Corley targeting larvae on this plant was successful, resulting in two reared adults (see paratypes).The existence of an Two reared specimens , show a grey-brown tinge in place of scattered dark scales and lack the row of terminal dots, but these features are shared by some of the Moroccan specimens.MNHN which was considered to be a possible aberration of A.mendesi Corley, 2002. As the signum is not known to be absent in any other Agonopterix species, it is extremely probable that this specimen belongs to A.carduncelli sp. n.Taxon classificationAnimaliaLepidopteraDepressariidaeBuchner & Junnilainensp. n.http://zoobank.org/8C70763C-9C9E-47CB-ABE7-F20B9271976C39\u00b051'N; 9\u00b03'E.Italy, Sardinia, Laconi, Italy, Sardinia, Laconi, 16.vi.2009, leg. J. Junnilainen, DNA barcode id. BC TLMF Lep 19306, gen. prep. DEEUR 4462, in coll. J. Junnilainen.\u2642, NHMUK; 1 \u2642, 1 \u2640, same data as holotype, leg. J. Junnilainen, in coll. M. Corley; 1 \u2640, Greece, Peloponnese, Chelmos, 2100 m, 10.vii.1963, leg. J. Klimesch, coll. ZSM; 1 \u2640, Italy, Puglia, 21.vii.1955, leg. S. Zangheri, in coll. ZSM; 1 \u2642, Italy, Puglia, \u201cFG\u201c Gargano sopra Vieste, 400 m, 5.ix.2008, coll. G. Fiumi; 1 \u2642, Italy, Sicilia, Madonie, Piano Battaglia, 18.x.1990, gen. prep. DEEUR 1928, in coll. TLMF; 1 \u2640, Italy, Latium, Mt Terminillo, 17.vii.2010, DNA barcode id. TLMF Lep 19067, gen. prep. DEEUR 1737, leg. & coll. T. Mayr; 1 \u2642, 1 \u2640, Italy, Puglia, Gargano, leg. larva 4.iv.2016 from Elaeoselinumasclepium, e.p. end of April 2016, leg., cult. & coll. P. Sonderegger.1 \u2640, same data as holotype, DNA barcode id. MM24152, leg. & coll. J. Junnilainen; 2 \u2642\u2642, 3 \u2640\u2640, same data as holotype, leg. & coll. J. Junnilainen; 1 \u2642, 1 \u2640, same data as holotype, leg. J. Junnilainen, in coll. ZMUH; 1 \u2642, 1 \u2640, same data as holotype, leg. J. Junnilainen, in coll. Diagnosis.A.pseudoferulae sp. n. . A.atomella Fig. and A.s70) Fig. , the two79) Fig. has redd000 Fig. , but herAdult: Wingspan 19\u201321 mm. Scales of head brown, tips markedly paler. Labial palp segment 2 inner side pale, outer and ventral sides medium greyish brown or rusty brown scales mixed with blackish scales; third segment bicoloured, blackish at base, shortly above middle and at extreme tip, pale between the dark areas. Antenna dark brown. Thorax with posterior crest, rather dark brown, tegulae similar. Forewing predominantly dark reddish brown, whitish and black scales interspersed in low (but variable) numbers, basal field markedly paler, gradually passing into a pale PageBreakstripe which runs along costa especially in proximal half and is interrupted by irregular dark patches. The centre of the forewing has the typical basic pattern of Agonopterix but with very distinct details: the two black, oblique dots partly bordered with reddish (brick-red to ochreous) scales which may connect the two dots on their proximal margin, distal margin pale to white, the third dot at about one-half with clear white centre and surrounded by a few dark scales, a brick-red to ochreous line connects the oblique dots with the distal dot and exeeds it a little; the diffuse blackish spot touches the brick-red line between the dots on the costal side. Cilia concolorous with wings. Under side of forewing dark grey except costa which is predominantly yellowish with interspersed PageBreakgroups of dark scales. Hindwing rather dark greyish brown, moderately translucent at base, cilia concolorous with wings, base and tips darker than in between. Legs covered with a mix of dark grey and pale scales, tibia yellowish to rusty brown on outer side, especially on fore- and hindlegs. Abdomen greyish, with broad dark line laterally and two rows of indistinct dark spots on ventral side.No gender-specific differences could be found.Variation: Little variation was found within the nine examined specimens. The number of interspersed white scales on forewing varies to some extent, and between the proximal pair of dots and the distal dot, an additional white dot may be developed or not. In one specimen the thorax (but not tegulae) is entirely black.Male genitalia , socii and gnathos of average shape, compare Figs lae Fig. belongs lla Fig. , A.oinoroa Fig. and A.slla Fig. anellus ana Fig. cuiller Female genitalia , signum narrow oval (4 times wider than long), rather large .lia Figs , 41a. AnA.pseudoferulae sp. n. also show distinct differences in female genitalia: A.ferulae ; MM24152 ; TLMF Lep 19067 .Neighbour-joining analysis shows Agonopterixatomella (BOLD:ABZ0059) as the nearest neighbour at a minimum of 2.45% p-distance. So far there are only sequences from the Italian population available, where no intraspecific divergence had been found, but this may change when Greek specimens are sequenced.For Maximum Likelihood analysis, see Fig. Related species: Searching for the most closely related species based on a neighbour-joining tree with a p-distance of 2.6% is also a Fabaceae-feeder, and the differences in genitalia are at least as marked as in A.atomella. On the other hand, the two PageBreakPageBreakbaceaeFa-feeders A.atomella and A.oinochroa have very similar male genitalia, but a barcode distance of 4.08%. This suggests that every single parameter must be handled with care. Pronounced similarity may result from being closely related, but it does not prove it, because a single distinctive feature may develop independently in different groups. The only certainty from present evidence is that A.pseudoferulae is not a cryptic species.ree Fig. , Maximumree Fig. and geniZSM in the Klimesch collection under A.ferulae. This was decisive for the species name pseudoferulae, which means \u201cthe false ferulae\u201d.The species name is a noun in genitive case. The first specimens of this new species were discovered in So far known from Italy and Greece. In Italy it had been collected from Mt Terminillo (Latium), Gargano (Puglia), Madonie, Piano Battaglia (Sicily) and Laconi (Sardinia) and in Greece from Chelmos (Peloponnese).Elaeoselinumasclepium (L.) Bertol. (Apiaceae) from Gargano, Italy. Unfortunately he was not expecting anything of great interest, so no photo or larval description was obtained. Larvae were collected on 4 April, while the moth emerged in late April. Moths in good condition have been caught in June and July, and a worn specimen has been caught in October. It remains unclear in which stage the species survives winter.Peter Sonderegger reared it from larvae collected on PageBreakZSM under the name Agonopterixferulae P. Buchner found a specimen collected by Josef Klimesch in Greece, which had a red mark in the discal cell which is not present in A.ferulae. Genitalia examination showed that it was distinct from A.ferulae and subsequently, when more recent specimens were found it was possible to obtain barcodes. Both genitalia and barcodes show this to be a new species not closely related to A.ferulae. It is described here as A.pseudoferulae.In Taxon classificationAnimaliaLepidopteraDepressariidaeBuchnerssp. n.http://zoobank.org/C90466AD-E3A7-4BF8-A452-ECFDD33E93EFSpain, Canary Islands, Tenerife, Guimar.Bupleurumaciphyllum [Bupleurumsalicifoliumssp.aciphyllum], ex. 16.iv.1907, Wlsm. 99748 | Walsingham Collection 1910-427 | B.M. \u2642 Genitalia Slide No. 23304, NHMUK010305296, coll. NHMUK.\u2642, Spain, Canary Islands, Tenerife, Guimar, 6.iii. DEEUR 2634, DNA-barcode id TLMF Lep 17692 , leg. & coll. K. Larsen,; 1 \u2640, Tenerife, Los Gigantes, 100 m, 8-11.i.2008, GP DEEUR 2807, DNA-barcode id TLMF Lep 17711 , leg. & coll. K. Larsen.1 \u2640, Spain, Canary Islands, Tenerife, Guimar, La Ladera, 800 m, 23.iv.1998, GP Depressariasaharae ssp. saharae . 1 \u2642, Spain, Granada, Sierra Nevada, 2430 m, 37\u00b06.23'N; 3\u00b023.84'W, 3.vii.2015, J. Tabell leg., GP \u2642 5480 J. Tabell, DEEUR 4024, DNA barcode id. TLMF Lep 19164 ; 1 \u2642, same collection data, without barcode; 2 \u2642\u2642, Teruel, Albarracin, Val de Vecar, 1100 m, 3.x.2015, leg. J. Viehmann, coll. W. Schmitz; 1 \u2642, Sr. de Albarracin, Sr. Alta, 1750m, 25.vi.2016, leg. J. Viehmann, coll. W. Schmitz; 3 \u2642\u2642, Teruel, Albarracin. 6 km env. 1.x.2008, GP DEEUR 1000 & 1005, leg. & coll. L. Srnka, 1 of them (GP DEEUR 1000) with DNA barcode id. TLMF Lep 07068 Introductory note. It may be considered unusual to give a detailed description of the nominate subspecies before the description of a new subspecies, but in this case the original Spanish description is not detailed enough to serve as the basis for a comparison of the two subspecies. The original description is completely without information on genetic data and has little on relationships of the new species.It is therefore necessary to include such information on the nominate subspecies in this investigation.D.saharae belongs to one of the basic patterns in the genus Depressaria which can also be found e.g. in D.ultimella Stainton, 1849 and D.daucella , with which this species was confused by Walsingham ). A situation which is often found in Depressaria is a combination of high intraspecific variability and near identical basic wing patterns used by several species, which makes it very difficult to determine specimens externally. When intraspecific PageBreakPageBreakvariability is larger than the mean difference between the species, identification may become impossible. On the other hand, most species of Depressaria have distinctive genitalia in both sexes. This is the case in D.saharae, where diagnosis must be based on genitalia: see relevant paragraphs below.The wing pattern of both subspecies of Depressariasaharaessp.saharae specimens from mainland Spain in D.bupleurella show some similarity, but with differences in many details; see comparison in Figs rae Figs are reallla Fig. , wide ; TLMF Lep 07068 ; TLMF Lep 17692 ; TLMF Lep 17711 .Neighbour-joining analysis shares a node in our NJ tree , this is not a surprise.sis Fig. shows inD.saharae belongs to the pastinacella group , named after D.pastinacella , now valid as D.radiella , which is characterised by the presence of a basal process of sacculus (clavus) and the absence or near absence of a distal process of sacculus (cuiller). Within this group, genitalia of both sexes clearly show D.bupleurella as closest species. Neighbour Joining tree and Maximum Likelihood analysis correspond with this estimation. The close relatedness of D.saharae and D.bupleurella is also supported by biology with both species (so far only known from ssp.tabelli) feeding on Bupleurum.Based on male genitalia, D.saharae - at this time still an undescribed species - in 2015 from the Spanish mainland, and sent specimens to Peter Buchner for study. They were essential to understanding this species and led to a search PageBreakfor females, which were found in collections from the Canary Islands and which are here treated as a separate subspecies.The subspecies name, a noun in the genitive case, honours Jukka Tabell, the Finnish lepidopterologist, who collected So far known only from Spain: Canary Islands (Tenerife).PageBreakBupleurumaciphyllum Sunding & G. Kunkel) from Canary Islands, Tenerife, Guimar. This plant is an endemic species of Macaronesia. The food-plant of D.saharaessp.saharae is unknown, but is likely to be another species of Bupleurum.Walsingham reared one moth from larvae collected on D.saharae was a simple drawing in literature: D.apiella: \u201c\u2026.According to Dr. Sattler, NHMUK London, this specimen belongs to a species near D.bupleurella or to a form of D.bupleurella. Dissection showed differences in costa of valva and in cuiller. It must be left to a later revision of this group to decide on the final status\u201d [translated from German]. Some males from Teruel, dissected by P. Buchner, showed this distinctive genitalia feature also. DNA barcoding supported the view that it was not a form of D.bupleurella, but a distinct species. As at this stage females were unknown, it remained undescribed.The first encounter with male genitalia of D.bupleurella, but showed a 6.36% p-distance in DNA-barcode, while barcodes show a 2% difference compared to D.saharae from Teruel, separating into two reciprocally monophyletic clusters. This suggested they were at least closely related, but left open PageBreakPageBreakthe question of conspecificity. A male reared by Walsingham from Tenerife in 1907 was the key to this so far unanswered question: it has genitalia like D.saharae from Teruel, but in external appearance is like the females from Tenerife. The lack of genitalic separation suggests that the Teruel and Tenerife specimens are conspecific, in spite of their different external appearance. The different external appearance of the Canary Island population, in combination with the corresponding external features of both sexes of the Canary Island population justify the treatment as two separate subspecies.In the large collection of Knud Larson, two females from Tenerife were found, which were both in external appearance and in genitalia patterns close to"} +{"text": "The following information is missing from the Funding section:https://grants.nih.gov/grants/guide/rfa-files/RFA-GM-17-002.html (grant number R35GM122561). Received by GB. Aveiro Institute of Biomedicine\u2014iBiMED www.ua.pt/ibimed . Received by MASS. Portuguese Foundation for Science and Technology (FCT) www.fct.pt and the European Structural funds (FEDER). Received by iBiMED and MASS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Dr. Rollin D. Hotchkiss Foundation. Received by ZB. NIH MIRA"} +{"text": "Scientific Data 4:170022 doi:http://dx.doi.org/10.1038/sdata.2017.22 (2017); Published 1 Mar 2017; Updated 27 Jun 2017The authors regret that Nicola Stevenson was omitted in error from the author list of the original version of this Data Descriptor. This omission has now been corrected in the HTML and PDF versions of this Data Descriptor, as well as the accompanying Corrigendum.ContributionsR.K., D.C., F.F. and J.K.V. designed and conceived the study. J.F., N.S. and F.F. performed experiments. J.K.V. performed all statistical and image analysis. R.K., J.K.V. and N.B. wrote the manuscript."} +{"text": "In Ho et\u00a0al. (2015), the author's name, Nathaniel J. Hubert, was incorrect and should have read, Nathaniel A. Hubert.We apologise for the typographical error."} +{"text": "Scientific Reports6: Article number: 2573610.1038/srep25736; published online: 05112016; updated: 09222016In this Article, the Acknowledgments section is incomplete.\u201cWe thank M. Sato, S. Hauf, G. R\u00f6del and the Yeast Genetic Resource Center for strains and plasmids; B. Schroth-Diez, Bert Nitzsche and Jan Peychl from the Light Microscopy Facility of MPI-CBG; V. Ananthanarayanan, M. Coelho, P. Delivani, D. Ramunno-Johnson and N. Maghelli for discussions and advice; I. \u0160ari\u0107 for the drawings; Human Frontier Science Program (HFSP) for financial support. A.-M.F. thanks the MPG for support by a postdoctoral grant through the MPG-CNRS GDRE \u201cSystems Biology.\u201dshould read:\u201cWe thank I. Kalinina, M. Sato, S. Hauf, G. R\u00f6del and the Yeast Genetic Resource Center for strains and plasmids; B. Schroth-Diez, Bert Nitzsche and Jan Peychl from the Light Microscopy Facility of MPI-CBG; I. Kalinina, V. Ananthanarayanan, M. Coelho, P. Delivani, D. Ramunno-Johnson and N. Maghelli for discussions and advice; I. \u0160ari\u0107 for the drawings; Human Frontier Science Program (HFSP) for financial support. A.-M.F. thanks the MPG for support by a postdoctoral grant through the MPG-CNRS GDRE \u201cSystems Biology.\u201d"} +{"text": "Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in\u00a0vitro and increased the rate of remyelination in\u00a0an ex\u00a0vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult\u00a0CNS progenitor cells involved in regeneration.The role of the neurovascular niche in CNS myelin\u00a0regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In \u2022CNS-resident PCs react to demyelination and are found close to differentiating OPCs\u2022PC-deficient mice show delayed OPC differentiation during CNS remyelination\u2022PC-conditioned medium accelerates OPC differentiation and enhances remyelination\u2022PC-derived LAMA2 induces OPC differentiation Following toxin-induced demyelination in PC-deficient mice and using a number of in\u00a0vitro approaches, Guzman de la Fuente et\u00a0al. show that CNS pericytes (PCs) respond to demyelination and, through Lama2 secretion, stimulate oligodendrocyte progenitor cell differentiation during remyelination. These findings extend PC function beyond vascular homeostasis toward regeneration. Although the adult mammalian CNS has a limited capacity for regeneration, lost oligodendrocytes and the myelin they produce are restored during remyelination. In response to demyelination, oligodendrocyte progenitor cells (OPCs) proliferate and migrate to the lesion, where they differentiate into remyelinating oligodendrocytes . RemyeliMyelination during development is strictly coupled to angiogenesis , where OWe first analyzed the proliferative response and localization of ECs and PCs following induction of white matter demyelination upon injection of ethidium bromide into the caudal cerebellar peduncles (CCPs) of adult rats A. In thiWe hypothesized that, if PCs and/or PLCs were involved in the differentiation of OPCs into remyelinating oligodendrocytes, then the differentiated cells would tend to be located in close proximity to PDGFRb+ cells. We therefore assessed the distance between Olig2+/adenomatous polyposis coli (APC)\u2212 OPCs and Olig2+/APC+ oligodendrocytes to the nearest PDGFRb+ cell at 14 dpl. We found that oligodendrocytes were preferentially located close to PCs, whereas OPCs showed no preferential clustering close to these cells; neither was there clustering of either OPCs or oligodendrocytes close to PLCs G and S1HPdgfbret/ret mice, in which a mutation in the retention motif of the Pdgfb gene causes a 75%\u201385% reduction in capillary PC coverage compared with heterozygous littermates , the density of mature oligodendrocytes (Olig2+/APC+) was lower and the density of OPCs (Olig2+/APC\u2212) higher than in control mice. However, on P17, no differences were observed in OPC differentiation and myelination , the number of PDGFRb+ increased substantially in both ret mice A\u2013S3F. Norol mice G\u2013S3I. Mirol mice J\u2013S3L, anrol mice M\u2013S3Q.Pdgfbret/ret mice compared with controls at 14 dpl. There was no significant difference in the number of Olig2+/APC\u2212 OPCs between Pdgfbret/ret and control mice and evaluated the rate of differentiation. MSC-conditioned medium (MSC-CM), previously identified as a strong inducer of OPC differentiation , was useWe next examined whether PCs can enhance remyelination. We used postnatal rat-derived cerebellar organotypic slice cultures as an ex\u00a0vivo model of remyelination . In thisPdgfbret/ret mice compared with control mice shows developmental delays in oligodendrocyte differentiation and the accumulation of OPCs, leading to defects in myelination in the corpus callosum , where they modulate inflammation or the formation of fibrotic scar tissue . Here wePdgfbret/ret mice (hetero- and homozygous), which were previously described by Animal experiments within this research have been regulated under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and\u00a0Ethical Review Body (AWERB) in accordance with United Kingdom Home Office regulations (Project License 70/7715) and in accordance with Austrian laws on animal experimentation and were approved by Austrian regulatory authorities . During this study, 2-\u00a0to 3-month-old Sprague Dawley rats and 12-week-old Preparation of CNS pericytes was performed following the Dore-Duffy protocol with modRemyelination of rat cerebellar slices was prepared as described previously . After 7U\u00a0tests were used when comparing one parameter. For statistical analysis with two parameters, such as time course experiments with different treatments, two-way ANOVA with Bonferroni post hoc was used. For distance frequency distribution analysis, chi-square test was used and SPSS 20 (IBM). Parametric one-way ANOVA, Tukey post hoc analyses, Student\u2019s t test, or Mann-Whitney was used G and S1HFor further details, see the S.L. and F.J.R. conceived the project. A.G.D.L.F., S.L., L.A., R.J.M.F., and F.J.R. designed the study. S.L., A.G.D.L.F., L.F.B., C.B., L.A., R.J.M.F., and F.J.R. wrote and edited the manuscript. S.L. and A.G.D.L.F. designed the figures. A.G.D.L.F., S.L., H.T., C.Z., A.K., G.A.G., L.D.C., M.A.M., J.A., C.B., R.J.M.F., L.A., and F.J.R. planned the experiments. A.G.D.L.F., S.L., M.E.S., P.v.W., P.R., O.E., C.Z., G.A.G., A.K., M.A.M., J.A., and L.D.C. conducted the experiments. A.G.D.L.F., S.L., M.E.S., H.T., A.T., P.R., A.O., L.B., A.K., M.A.M., J.A., and F.J.R. collected data. A.G.D.L.F., S.L., M.E.S., G.A.G., L.D.C., C.Z., P.R., A.T., L.H., A.K., M.A.M., and J.A. analyzed data. A.G.D.L.F., S.L., P.R., G.A.G., A.K., M.A.M., J.A., C.B., R.J.M.F., L.A., and F.J.R. interpreted data. H.T., A.T., P.R., A.O., P.Z., S.C.D., and L.B. assisted technically. R.J.M.F., L.A., and F.J.R. supervised the project. C.B., L.A., R.J.M.F., and F.J.R. supported this study financially."} +{"text": "Scientific Reports 10.1038/s41598-017-08562-1, published online 11 August 2017Correction to: The original version of this Article incorrectly listed Xuan Wu, and not Xiakong Liu, as a corresponding author. The correct corresponding authors for this Article are George Y. Chen, Xiaokong Liu and Haolan Xu. Correspondence and request for materials should be addressed to G.Y.C. (email: george.chen@unisa.edu.au) or X.L. (email: xiaokong.liu@unisa.edu.au) or H.X. (email: haolan.xu@unisa.edu.au). This error has now been corrected in the HTML and PDF versions of the Article."} +{"text": "Scientific Reports 10.1038/s41598-017-16674-x, published online 27 November 2017Correction to: Ehtesham Iqbal and Zina M Ibrahim were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and the accompanying Supplementary Information.The Author Contributions section now reads:D.B., H.W. and R.J.B.D. designed the study. O.D. advised on validation. H.W. and E.I. processed EHR data. D.B. designed the prediction algorithm, performed analysis and prepared the manuscript. R.J.B.D., Z.M.I., M.B. and R.S. supervised the project. All authors reviewed the manuscript.In addition, the original version of this Article contained an error in Reference 16.et al. Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register. PLoS One 10, 1\u201314 (2015).\u201d\u201cIqbal, E. now reads:et al. ADEPt, a semantically-enriched pipeline for extracting adverse drug events from free-text electronic health records. PLoS One 12, 1\u201316 (2017).\u201d\u201cIqbal, E."} +{"text": "Scientific Reports 10.1038/s41598-017-12175-z, published online 20 September 2017Correction to: In the original version of this Article, the authors Ifedayo M.O. Adetifa and Suzanne T.B Anderson were incorrectly indexed. This error has now been corrected."} +{"text": "Leptolalax macropssp. nov. is distinguished from its congeners by a combination of the following morphological attributes: (1) body size medium ; (2) supra-axillary glands present, creamy white; ventrolateral glands indistinct; (3) tympanum externally distinct; (4) dorsal skin roughly granular with larger tubercles, dermal ridges on dorsum absent; (5) rudimentary webbing present between fingers I\u2013II and II\u2013III; rudimentary webbing between all toes; fingers and toes without dermal fringes; (6) in life ventral surface greyish-violet with white speckling; (7) supratympanic fold distinct, dark brown in life; (8) iris bicolored, typically golden in upper half, fading to golden green in lower half; (9) tibia short ; and (10) eyes large and protuberant . From all congeners for which comparable sequences are available, the new species differs markedly in the 16S rRNA mitochondrial gene sequence (P-distance>5.7%). The new species is currently known only from montane evergreen tropical forests of Song Hinh District, Phu Yen Province, and M\u2019Drak District of Dak Lak Province at elevations of 470\u2013630 m a.s.l.. We suggest the new species should be considered as Data Deficient following the IUCN\u2019s Red List categories. We also report a previously unknown Leptolalax mtDNA lineage from an evergreen tropical forest in the Hoa Thinh District of Phu Yen Province, which may also represent an undescribed species.We describe a new species of megophryid frog from Phu Yen Province in southern Vietnam. LeptolalaxLeptolalax species diversity has strikingly increased in recent decades, from only four in 1983 inhabiting the southern and central parts of the Annamite (or Truong Son) Mountains in southern Indochina . Sexes were separated for subsequent comparisons among samples. One-way analysis of variance (ANOVA) and Duncan\u2019s post-hoc tests were used for morphometric comparisons. A significance level of 95% was used of all statistical tests.Leptolalax and (when available) photographs of these specimens in life (L. hamidi Matsui (L. heteropus (Boulenger) ; L. hamii Matsui ; L. heteulenger) ; L. isos& Emmett ; L. kaja Youmans ; L. kalolonensis ; L. kecid & Yong ; L. khas& Hooroo ; L. latenderson) , L. lauig & Wang , L. liuiFei & Ye , 2010; Laculosus ; L. maoeey & Che ; L. marmishikawa ; L. maur& Yambun ; L. melas Matsui ; L. meli melicus , 2016; L(Taylor) ; L. nahalov & Ho ; L. nokrw & Sen) ; L. nyx & Dubois ; L. oshais (Liu) ; L. pallpallidus ; L. pelooulenger ; L. petr& Nguyen ; L. pict Malkmus ; L. plat Dehling ; L. pluvGrosjean , 2011, Lau & Cao ; L. pyrrpyrrhops ; L. saba& Yambun , L. solus Matsui ; L. sunglov & Ho ; L. taduungensis ; L. tamdas & Das ; L. tengen & Rao ; L. tubeDarevsky ; L. vent Ye & Li ; and L. ej & Che . Howeverej & Che , 2016, wLeptolalax . The PCRreverse) . The ampMG787993 .L. applebyi species group, we used 32 published sequences of 16S rRNA between sequences and species were calculated using MEGA 7.0 values of 70% or greater and Bayesian posterior probabilities (BI PP) values over 0.95 as sufficiently resolved and maximum likelihood (ML) algorithms. The BI analyses were conducted in MrBayes v.3.1.2 ; Metroporesolved . The ML Leptolalax sequences. The final alignment consisted of 1 075 sites, with 617 conserved sites and 413 variable sites, 139 of which were parsimony-informative; the transition-transversion bias (R) was estimated as 2.14 . Substitution rates were estimated under the General Time Reversible (GTR) model (+I+G). Nucleotide frequencies were A=31.23%, T=24.47%, C=24.27%, and G=20.03%.The 16S rRNA dataset contained 39 ingroup and five outgroup Phylogenetic analysis results of the 16S rRNA gene fragment are shown in L. applebyi species group and the presence of two major lineages within it. Clade I encompassed three species inhabiting the Tay Nguyen (Kon Tum) Plateau in central Vietnam and northeastern Cambodia: namely, L. applebyi, L. ardens, and L. melicus (L. applebyi group species from the Langbian (Da Lat) Plateau of the Southern Annamite Mountains. Phylogenetic relationships within Clade II were not sufficiently resolved: there was a tendency toward a more distant position for L. pyrrhops and L. maculosus, with the remaining lineages forming a monophyletic group (0.95/70). The two newly discovered populations of Leptolalax sp. from Phu Yen Province formed two independent mtDNA matrilines: that is, the Hon Den Mt. lineage and Hoa Thinh lineage. The sequence of Leptolalax sp. from Dak Lak Province to 10.3% (between L. applebyi and L. pyrrhops) of substitutions. The uncorrected genetic P-distances in the ingroup and outgroup comparisons partly overlapped: genetic distances between the L. applebyi group members versus the Leptolalax taxa outgroup ranged from 9.2% to 15.4% .The uncorrected Leptolalax sp. from Hon Den Mt., Song Hinh District, was clearly distinct from all other group members in the examined 16S rRNA fragment sequences and appeared to be most closely related to L. bidoupensis from the eastern edges of Langbian Plateau (Lam Dong and Khanh Hoa provinces) and to a Leptolalax sp. population from Hoa Thinh, Tay Hoa District (Phu Yen Province) (P-distance=5.7% for both comparisons). The Leptolalax sp. population from Hoa Thinh was genetically closer to L. bidoupensis and L. pallidus, with a P-distance value of 4.5% (both species from eastern Langbian Plateau).The newly discovered population of L. applebyi group .P-distances were 0.0% in the Leptolalax sp. population from Hoa Thinh, and 0.1% in the Leptolalax sp. from Hon Den Mt.; the five examined specimens of the latter species of Leptolalax from Dak Lak and Phu Yen provinces had two haplotypes of the 16S rRNA gene fragment.Intraspecific genetic Leptolalax sp. from Song Hinh (Hon Den Mt.) and Tay Hoa (Hoa Thinh) districts of Phu Yen Province belong to two independent mtDNA lineages, clearly distinct from each other and from the remaining members of the L. applebyi species group. Despite geographical proximity (~30 km between Hon Den Mt. and Hoa Thinh), these two localities cradle distinct species of Leptolalax, and both appear to be new to science. These two potentially new species were assigned to the Langbian Plateau clade of the L. applebyi species group and appear to be closely related to L. pallidus, L. kalonensis, and L. bidoupensis. At the same time, the population of Hon Den Mt. appears to be conspecific to a Leptolalax sp. found in the eastern part of Dak Lak Province .Our molecular data clearly indicated that the two recently discovered populations of Leptolalax sp. population of Hoa Thinh (Tay Hoa District) as a candidate new species sensuLeptolalax from Hon Den Mt. in Phu Yen Province of southern Vietnam clearly represents a new species, which we describe as follows.Lacking enough material for morphological comparisons, we tentatively indicate the Leptolalax macrops sp. nov.Chresonymy:Leptolalax sp. [molecular lineage 7] \u2014 Holotype: PYU DTD-508 (field no. DTD-0508), adult male collected from Suoi Khi Stream, Hon Den Mt., Ea Ly and Ea Trol Commune border, Song Hinh District, Phu Yen Province, Vietnam (N12Paratypes: IEBR A.2017.9 (field no. DTD-507) and ZMMU A-5823 (field no. DTD-510), two adult males, and PYU DTD-509 (field no. DTD-509), one adult female, collected from the same locality as the holotype at elevations between 471 and 630 m a.s.l. by Dang Trong Do on 18 August 2015 from 1900 h to 2300 h.Diagnosis: The species is assigned to the genus Leptolalax based on the following characters: (1) finger tips rounded; (2) elevated inner metacarpal tubercle present, not continuous onto thumb; (3) body with macroglands ; (4) vomerine teeth absent; (5) tubercles on eyelids present; and (6) anterior tip of snout with whitish vertical bar body size medium ; (2) supra-axillary glands present, creamy white; ventrolateral glands indistinct; (3) tympanum externally distinct; (4) dorsal skin roughly granular with larger tubercles, dermal ridges on dorsum absent; (5) rudimentary webbing present between fingers I\u2013II and II\u2013III; rudimentary webbing between all toes; fingers and toes without dermal fringes; (6) in life ventral surface greyish-violet with rare white speckling; (7) supratympanic fold dark brown; (8) iris bicolored, typically golden in upper half, fading to golden green in lower half; (9) tibia short (TbL/SVL 0.44\u20130.45); and (10) eyes large and protuberant (ED/SVL 0.15\u20130.16). The new species is also markedly distinct from all congeners for which comparable 16S rRNA mitochondrial gene sequences are available (uncorrected genetic P-distance>5.7%).ical bar . LeptolaEtymology: Specific epithet \u201cmacrops\u201d is a noun in the nominative case, derived from Greek \u201cmacros\u201d for \u201clarge\u201d and \u201cops\u201d for \u201ceye\u201d, in reference to its comparatively large eye size.Recommended vernacular names: We recommend \u201cBig-eyed Litter Frog\u201d as the common English name of the new species and the common name in Vietnamese as \u201cC\u00f3c m\u00e0y m\u1eaft to\u201d.Description of holotype: Medium-sized Leptolalax specimen (SVL 28.0 mm); body and head in good state of preservation, fingers and toes partially dehydrated due to ethanol preservation , top of head weakly concave; snout short (E-S/HL 34.2%), slightly projecting beyond margin of lower jaw; slightly truncated in dorsal view ; border between inner and outer metacarpal tubercles indistinct; fingers in life lack dermal fringing, basal webbing present between fingers I and II and fingers II and III, absent between fingers III and IV ; tibiotarsal articulation of adpressed limb reaching eye-level; toe tips round in life, slightly truncate in ethanol preservative due to partial dehydration; relative toe lengths: I